PMID- 1853738 TI - [The consent of the patient]. PMID- 1853737 TI - The P300 component of the auditory event-related potential in monozygotic and dizygotic twins. AB - The P300 component of the auditory event-related potential was recorded from 10 pairs of monozygotic (MZ) twins and 11 pairs of dizygotic (DZ) twins during an auditory discrimination task. The within-pair similarity of P300 latency was significantly greater in MZ than in DZ twins. The within-pair similarity of P300 amplitude was not significantly greater in MZ than in DZ twins. These results support previous findings suggesting that P300 latency is largely genetically determined. PMID- 1853739 TI - [Tooth injuries during general anesthesia, oral endoscopy and vibro-massage]. AB - It is generally recognized that dental injury during and after tracheal intubation is a significant problem. Damage may occur during oro-tracheal intubation, oral endoscopy or seismotherapy. The incidence was reported in a study conducted in the contentious department of Lyon hospitals, in France, from 1978 to 1988. Results confirm that damage is relatively common and that the majority of damaged teeth (67%) were known to have been previously restored, or weakened through periodontal disease prior to the damage occurring. Maxillary incisors were the most frequently injured teeth. Fracture of crowns and roots of natural teeth (44,8%), followed by partial luxation (20,8%) and avulsion (20,8%) were the most common injury. Several cases are presented which reveal the clinical value of dental damages that occur during orotracheal intubation, oral endoscopy or seismotherapy. Besides dental or gingival complications can appear immediately but also after a few days or weeks. Some of the most recent development in dental therapy such as the butterfly bridge, titanium implants and porcelain laminate veneers are described. Tooth protective guards must be put into widespread use. Legal implications of dental lesions occurring during oro tracheal intubation, oral endoscopy or seismotherapy are presented. PMID- 1853740 TI - [The Akinosi dental anesthesia technique: apropos of 10 clinical cases]. AB - The anesthesia technique described by AKINOSI in 1977, in Nigeria, shows certain advantages: According to the author, it has a percentage of efficacy, of about 95%. It permits an effective anesthesia of the inferior alveolar, lingual and buccal nerves to be obtained with a single injection. It has a psychological aspect which is of interest to the degree that it is carried out with the mouth closed, the patient thus being in a position of muscular and aponeurotic relaxation, which permits a nearly painless injection to be made. This technique has disadvantages which lead to a preference for the "Spix spinal" technique, each time that it is indicated; the onset is longer than the one at the Spix an average of 6 minutes (for all nerves) as seen in this study, but above all, it is a high vascular risk technic that can be conceived only if perfect knowledge of the pterygo-mandibular region has been gained so as to evaluate the vascular proximities, essentially the maxillary artery and the pterygoid veinous plexas. PMID- 1853741 TI - [Immediate effects of irradiation of the orofacial area on the pH of salivary lactobacilli]. AB - pH and salivary lactobacilli were analysed in 22 healthy individuals and 34 patients with cancer tumors of the oral or oropharyngeal regions before and during irradiation therapy. The findings revealed in cancer patients before radiotherapy, that pH and lactobacilli were significantly lower than those in non cancer control subjects. During irradiation therapy, pH and lactobacilli were not significantly altered. No significant difference was found between patients cured by chemotherapy before radiotherapy and patients treated only by irradiations. However, pH is modified by teeth: toothless patients ph and toothed patients pH change in opposite direction. PMID- 1853742 TI - ["Food" granuloma of the jaws. Presentation of a new case and review of the literature]. AB - The clinical observation of an oral pulse granuloma allows to detail the clinical and pathological characteristics of this lesion. The etiology of this particular granuloma is explained by the introduction of alimentary particles into maxillary bone. A review of the literature about this subject is also made. PMID- 1853743 TI - [Clinical form of preparations and prosthetic restoration after hemisection and root amputation]. AB - With the expand of periodontology and present tendency to preserve the teeth, are appear news line forms for our preparations (of fixed prosthodontics). After hemisection or root-amputation, we are found of prosthetic reconstruction problem. This one should have to respect some simple principles on account of characteristic contour form of tooth after surgery. It must be important to have good indications, perfect execution, and meticulous realisation of provisionally prosthetic. PMID- 1853744 TI - [The use of general drugs other than antibiotics in periodontitis]. AB - Outside of the antibiotics, numerous general medications are prescribed in the context of the treatment of periodontal diseases. It appeared to be of interest to study them. The international research on anti-inflammatory drugs will be analysed in the literature. An in-depth study will then be carried out on documents provided by laboratories which market products likely to be active on periodontal diseases in France. All the publications concerning Imudon, Piascledine 300 and Insadol will be more particularly analysed. The operative protocols, conditions and experimentation, as well as the results, will be studied as objectively as possible so as to determine the essential efficacy of one or nother product. PMID- 1853745 TI - [Palatal groove in premature newborns]. AB - Prolonged intubation for very low birth weight neonates induces the formation of a palatal groove. Intraoral appliances are used to prevent this complication. However, it still exists inhalation and ingestion risks when an impression is taken. Irritation of the skin of the upper lip when using a surgical tape to secure the tube is usual. This article deals with modifications brought to avoid such disadvantages. PMID- 1853746 TI - [Lesions of the oral cavity induced by chewing tobacco]. AB - Currently, in France, chewing tobacco has only a small place amongst the factors of tobacco intoxication. The same is not true for North Africa, where it is very widely used, and in the United States, where it is enjoying considerable popularity. The consequences of this type of tobacco intoxication can be severe for the oral cavity: reactional keratosis, gingival retraction, dental coating, periodontitis, risk of malignant degeneration. The public health services must be warned of the dangers of this form of tobacco intoxication. PMID- 1853747 TI - [Self-medication in dentistry]. PMID- 1853748 TI - [Intrinsic chemical stability of resins for removable dentures]. AB - This article begins by recalling the notions of biocompatibility and bio material, in order to define the general context of the research on the intrinsic chemical inertia of resins used for removable prostheses. The materials (10 resins), equipment and operating conditions set up to obtain the extraction liquids which are analysed according to three procedures are then treated: molecular absorption spectrophotometry under ultra-violet rays, gas phase chromatography, coupled with mass spectrometry and atomic absorption spectrometry. Gas phase chromatography coupled with mass spectrometry showed that only one resin released diethyl phthalate after an immersion duration of 8 weeks. Various propositions are discussed in order to try to explain these various behaviours. In conclusion, it appears at the end of this investigation that the resins tested (except for one) show good intrinsic chemical stability when they are used according to precise and rigorous procedures. PMID- 1853749 TI - [Furcation lesions in deciduous teeth]. AB - The area of furcation of temporary molars constitutes a zone of exchanges and rearrangements relating to the evolution of the sub-adjacent permanent tooth. It is subjected to the eruption of the latter and to the physiological modifications of the temporary tooth. Moreover, this area is the site of above-mentioned inflammatory or infections conditions, maintained or aggravated by anatomical factors (accessory canals, thin pulpar floor, with little calcified dentine and broad tubuli), physiological factors (multiplication of accessory canals, decrease in the floor and migration of the epithelial attachment), endodontic factors (pulpal involvement and its complications) and periodontal factors (septum syndrome). The pathology of furcation is an evolving lesion. When discovered early it can be treated by endodontic therapy, while, in a later phase, it will require the extraction of the tooth. The assessment is made on the basis of a X-Ray examination which permits the temporary tooth to be situated in its stable or labile phase, the condition of the pulpal floor to be evaluated and the stage of sub-adjacent germ mineralisation to be estimated. A periodontal arrangement, by coronal reconstitution, conditions the reliability of the endodontic therapies. PMID- 1853751 TI - Amyotrophic lateral sclerosis and other motor neuron diseases. PMID- 1853750 TI - [Precise mucostatic primary impression taking in the edentulous mandible. Hemi arch method]. AB - The author has shown that any impression material and its support in the mouth must be more malleable than the material used for the object to be reproduced. From a fall mandibular arch the impression of both sides, left and right, are taken successively by hemi-impressions without impression trays. Two individual half impression trays are made, placed in the mouth and are joined together using an auto-polymerizing resin. The resulting individual tray permits to make a perfect mucostatic impression. This method, far from taking more time, is a time saver, since the touch-ups to the individual tray and then to the finished prosthesis are practically non-existent or considerably reduced. PMID- 1853753 TI - Spinal muscular atrophies: how many types? PMID- 1853752 TI - The neuronal cytoskeleton in disorders of the motor neuron. PMID- 1853754 TI - Spinal monomelic amyotrophy. PMID- 1853755 TI - Juvenile amyotrophic lateral sclerosis and related syndromes. PMID- 1853756 TI - Genetic analysis of childhood-onset spinal muscular atrophy. PMID- 1853757 TI - A candidate gene for X-linked spinal muscular atrophy. PMID- 1853758 TI - Gene linkage in familial amyotrophic lateral sclerosis: a progress report. PMID- 1853759 TI - Molecular genetics of familial amyotrophic lateral sclerosis. PMID- 1853760 TI - Amyotrophic lateral sclerosis mortality rates in Harris County, Texas. PMID- 1853761 TI - Risk factors in amyotrophic lateral sclerosis. PMID- 1853762 TI - Lineage analysis with a recombinant retrovirus: application to chick spinal motor neurons. PMID- 1853763 TI - Amyotrophic lateral sclerosis/parkinsonism-dementia complex in southern Guam: is it disappearing? PMID- 1853764 TI - Ten central themes in a decade of ALS research. PMID- 1853765 TI - Role of the cycad neurotoxin BMAA in the amyotrophic lateral sclerosis parkinsonism dementia complex of the western Pacific. PMID- 1853766 TI - Experimental models of aluminum-induced motor neuron degeneration. PMID- 1853767 TI - Post-radiation motor neuron syndromes. PMID- 1853768 TI - Immunogenetics and motor neuron disease. PMID- 1853769 TI - Immune-mediated models of motor neuron destruction in the guinea pig. PMID- 1853770 TI - Trophic factors for cultured lower motor neurons. PMID- 1853771 TI - Separating motor neuron diseases from pure motor neuropathies. Clinical clues and definitions. PMID- 1853772 TI - Separation of motor neuron diseases from pure motor neuropathies: pathology. PMID- 1853773 TI - Separating motor neuron diseases from pure motor neuropathies. Multifocal motor neuropathy with persistent conduction block. PMID- 1853774 TI - Autoimmunity and ALS: a comparison of animal models of immune-mediated motor neuron destruction and human ALS. PMID- 1853775 TI - Motor neuron syndromes and monoclonal IgM antibodies to gangliosides. PMID- 1853776 TI - Retrograde axonal transport and transcytosis of immunoglobulins: implications for the pathogenesis of autoimmune motor neuron disease. PMID- 1853777 TI - Paraneoplastic motor neuron disease. PMID- 1853778 TI - Viruses and motor neuron diseases. PMID- 1853779 TI - Post-polio syndrome: concepts in clinical diagnosis, pathogenesis, and etiology. PMID- 1853780 TI - Clinical trials in ALS: measurement and natural history. PMID- 1853781 TI - Design of clinical therapeutic trials in amyotrophic lateral sclerosis. PMID- 1853782 TI - Human and rodent spinal cord neurons in culture. PMID- 1853783 TI - Nuclear and cell body size in spinal motor neurons. PMID- 1853784 TI - Skeletal muscle proteins rescue motor neurons from cell death in vivo. AB - Because embryonic neurons are more sensitive to the effects of target derived factors than adult neurons, the developing nervous system provides a sensitive model for investigating the in vivo actions of target-derived growth factors. We have used the developing chick embryo to document that skeletal muscle contains substances that selectively enhance the in vivo survival of motor neurons. We have also shown that a single purified skeletal muscle protein (CDF) is capable of rescuing motor neurons during the period of naturally occurring cell death. The rescue of motor neurons in vivo by CDF is consistent with the hypothesis that distinct neurotrophic factors exist which regulate the timing and extent of the naturally occurring death of specific populations of neurons. The effects of CDF appear to be specific for cholinergic somatic motor neurons, since the survival of other types of spinal cord neurons, which also exhibit cell loss during the treatment period, was not affected by CDF treatment. In contrast, treatment of the embryos with extracts of tissues not innervated by motor neurons, or with NGF or bFGF, does not affect motor neuron survival. Thus the ability to rescue motor neurons during the period of cell death appears to be a distinct property of CDF and provides indirect evidence that this molecule may play a role in the survival and development of motor neurons. The role of neurotrophic factor involvement in the pathophysiology of degenerative diseases such as ALS remains entirely speculative. However, the demonstration that such factors affect the neuronal subtypes at risk in these diseases provides experimental support for this possibility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1853785 TI - Immunology and clinical importance of antiphospholipid antibodies. AB - Having reviewed the literature on the association of aPL antibodies with clinical manifestations, it is clear that this group of autoantibodies are of considerable importance. The presence of aPL antibodies in some but not all individuals confers a risk of a clinical syndrome characterized by recurrent arterial or venous thrombosis, thrombocytopenia, hemolytic anemia, or positive Coombs' test, and in females, recurrent idiopathic fetal loss. In SLE, the risk is approximately 40%, compared with a risk of 15% in the absence of aPL antibodies. However, only one half of persons possessing these antibodies have SLE, and overall the risk is around 30%. In some circumstances, such as in chlorpromazine or infection-associated aPL antibodies, there appears to be no increased risk. At the other end of the spectrum are seen patients whose only clinical manifestations comprise features of this clinical syndrome, and this entity has been designated the primary antiphospholipid syndrome (PAPS). aPL antibodies are also important because they are not uncommon. They have been found frequently in women with idiopathic recurrent fetal loss (30%), in non-autoimmune patients with ischemic heart disease (20%), or venous thrombosis (up to 30%), or stroke (4 47%), and in chronic immune thrombocytopenia (30%). These autoantibodies can be detected using sensitive solid-phase immunoassays employing the CL antigen, or in appropriate coagulation tests to detect LA activity. These assays are simple to perform but require care in selection of the best test and in interpretation of results. Current tests do not distinguish between those persons at risk of the clinical events and those not at risk. Detection of specific isotypes (especially IgG) and antibody level may aid in such a designation. Treatment of aPL antibody associated syndromes remains a controversial subject. Since thromboses are associated with significant morbidity and potential mortality, there is a good argument for long-term preventive antithrombotic therapy, at least for as long as the antibodies are detectable, in those patients in whom clinical complications have previously occurred. It is not generally recommended that this treatment be offered to individuals in whom aPL antibodies are detected but who have not suffered previous thromboses, since the risk of such events does not appear to be equal within a group of aPL antibody-positive persons. This particularly applies to pregnant women, since live births and uncomplicated pregnancies are observed regularly in the presence of aPL antibodies without specific treatment. A previous history of at least one unexplained, late fetal loss is considered a prerequisite before intervention in subsequent pregnancies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1853786 TI - Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells. PMID- 1853787 TI - The euthyroid sick syndrome. PMID- 1853788 TI - Cost of continuing-care facilities in the evaluation of experimental national health service nursing homes. AB - In this paper the costing method and results from the UK evaluation of National Health Service (NHS) nursing-home and continuing-care hospital accommodation for elderly people are presented. Results demonstrate that, in deciding on the relative efficiency of NHS nursing-home and hospital accommodation, it should be possible to provide NHS nursing-home care at a cost which is no greater than its hospital counterpart. Cost implications of future developments should be monitored in the possible event that they are set up differently from the NHS nursing homes discussed in this paper. Despite being more costly than private sector nursing-home accommodation, NHS nursing homes cater for a less able group of people, although some overlap exists. The implications of such results are discussed in the light of the UK Government's recent proposals to reform both the NHS and community care. PMID- 1853789 TI - The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune function in elderly long-stay patients: a randomized controlled trial. AB - Thirty elderly long-stay patients were randomly allocated to receive either placebo or dietary supplementation with vitamins A, C and E for 28 days. Nutritional status and cell-mediated immune function were assessed before and after the period of supplementation. Following vitamin supplementation, cell mediated immune function improved as indicated by a significant increase in the absolute number of T cells (p less than 0.05), T4 subsets (p less than 0.05), T4 to T8 ratio (p less than 0.01) and the proliferation of lymphocytes in response to phytohaemagglutinin (p less than 0.01). In contrast, no significant changes were noted in the immune function of the placebo group. We conclude that supplementation with the dietary antioxidants vitamins A, C and E can improve aspects of cell-mediated immune function in elderly long-stay patients. PMID- 1853790 TI - Visual acuity and contrast sensitivity in relation to falls in an elderly population. AB - Visual acuity and contrast sensitivity were measured in 95 residents of a hostel for the aged (mean age = 83 years) using a dual-contrast letter chart and the Melbourne Edge Test (MET). Vision (as measured by visual acuity, the MET, low contrast visual acuity, and difference between high- and low-contrast acuity) decreased significantly with age and all four measures were significantly correlated. Subjects with a clinical eye disorder had poorer vision than those without a disorder although the differences were not significant. Visual acuity and contrast sensitivity were not associated with body sway when subjects were standing on a firm base. However, when the subjects were placed in a situation which provided reduced support (standing on a compliant surface), body sway was associated with poor visual acuity and contrast sensitivity. There was also a difference in contrast sensitivity between those who fell one or more times in a year of follow-up and those who did not fall. It appears that reduced vision may be a predisposing factor to postural imbalance and falls in elderly persons. PMID- 1853791 TI - Changing patterns of therapeutic agents in the elderly: a ten-year overview. AB - Drug use patterns in a large ambulatory elderly population were studied cross sectionally over a 10-year period. There were 24192 drug histories obtained on 4509 individuals during the period from 1 August 1978 to 31 July 1988. The average number of drugs used per person increased from 3.22 in 1978-9 to 3.94 in 1987-8. Prescribed drug use increased by 0.52 per person compared with an increase of 0.21 for nonprescribed medication. Analysis of two mutually exclusive groups of participants from 1978-9 and 1987-8 revealed a significant (p less than 0.0001) increase in the use of nonprescribed medication but no significant increase in the use of prescribed medication after adjusting for age and sex effects. The four most frequently used therapeutic classes of drugs in 1978-9 as a percentage of all drugs used were antihypertensives (10.8%), analgesic antipyretics (6.4%), antirheumatic (6.4%), and cathartics (5.4%) compared with the antihypertensives (9.5%), analgesic-antipyretics (5.9%), anticoagulants (5.5%), and antirheumatic (4.6%) for the 1987-8 period. PMID- 1853792 TI - Helicobacter pylori infection in elderly dyspeptic patients. AB - The association between Helicobacter pylori (HP) and gastritis is well established. As there is evidence that HP infection increases with age we reviewed the clinicopathological records of 119 consecutive patients aged 65-85 years (mean 71.1 years) on whom gastroscopy had been performed for dyspeptic symptoms. All patients had two antral biopsies--one was assessed for histological evidence of gastritis and the other was independently assessed for evidence of HP infection. Thirty-six patients (30%) had duodenal ulceration, of whom 32 (89%) had an associated HP-positive gastritis. Forty-nine patients (41%) had antral gastritis without ulceration, of whom 38 (78%) were HP positive and 11 (22%) were HP negative. Ninety-one per cent of HP-negative gastritis patients had a history of recent ingestion of non-steroidal anti-inflammatory drugs (NSAID) compared with 29% of HP-positive gastritis patients. Ten patients (8%) had normal antral mucosa but had evidence of reflux oesophagitis (one of these patients was HP positive). Nineteen patients (16%) had normal antral mucosa and normal endoscopic findings and one of these was HP positive. We conclude that HP infection is associated with the majority of cases of symptomatic gastritis in elderly patients. HP-positive gastritis is associated with the majority of duodenal ulcers. The most important cause of HP-negative gastritis is NSAID ingestion. PMID- 1853793 TI - The febrile response to mild infections in elderly hospital inpatients. AB - We studied 74 patients whose temperature was normal according to nurses' temperature charts and who were not on antibiotic treatment. The subjects were inpatients whose condition had deteriorated on the ward, or patients admitted the previous day in whom no diagnosis had been established. One simultaneous set of measurements was made of sublingual, rectal, axillary and proximal auditory canal temperatures. A fever was recorded in 63 of 74 patients (85%); 54 febrile patients had a raised rectal temperature, and 54 had a raised proximal auditory canal temperature; 60 patients were febrile at one or both of these sites. A further three patients had raised sublingual temperatures alone. All patients who were regarded as being definitely or probably infected were febrile at one or more sites. Eighty-one per cent of those considered to be possibly infected, and 71% of those with no clinical evidence of infection were also febrile. Rectal and proximal auditory canal temperatures can each detect fever in approximately 86% of febrile patients, sublingual temperature in 66%, and axillary temperature in 32%. Rectal temperature is clinically the most useful temperature measurement in elderly patients. We conclude that significant infections in patients in a warm environment result in a fever which often remains undetected when only sublingual temperature is measured. PMID- 1853794 TI - A comparison of single-dose versus conventional-dose antibiotic treatment of bacteriuria in elderly women. AB - The efficacy of single-dose antibiotic therapy for the treatment of bacteriuria in a group of non-catheterized elderly women was compared with that of conventional 7-10 day courses of antibiotic therapy. Thirty-one women received single-dose treatment and 22 conventional-dose treatment. The cure rates at 1 and 6 weeks for the single-dose treatments were 52% and 38%, respectively, and the cure rates for the conventional-dose treatments at 1 and 6 weeks were 59% and 52%, respectively. It is concluded that there may be a place for the use of single-dose antibiotic therapy for the treatment of selected elderly women with bacteriuria, but larger studies are needed. PMID- 1853795 TI - Functional assessment in severely demented patients. AB - The Brighton Clinic Adaptive Behaviour Scale was administered to a group of severely demented patients, resulting in a range of scores. The scale was found to be reliable and validated against the Clifton Assessment Procedures for the Elderly Behaviour Rating Scale and psychiatric ratings. The scale is likely to prove useful to clinicians and researchers. PMID- 1853796 TI - Review: deterioration of glucose tolerance with age: the role of insulin resistance. AB - Glucose tolerance is determined by the balance of insulin secretion and insulin action and deteriorates with age. Insulin secretion does not appear to be reduced with increasing age, but many recent studies have demonstrated insulin resistance in healthy elderly subjects. However, this has not been a universal finding and the reasons for the discrepant results probably include general health, physical training, changes of liver size and delays in carbohydrate absorption. When confounding factors, particularly physical activity, are taken into account there appears to be little or no change in insulin action with age. Delays in monosacharride absorption may play a role. Maintaining physical fitness throughout middle and older age and so reducing hyperinsulinaemia may have benefits on reducing vascular disease. PMID- 1853797 TI - Serum cholesterol and coronary heart disease. PMID- 1853798 TI - The biliary tract: imaging for the 1990s. PMID- 1853799 TI - Characterization of tumor hypoxia by 31P MR spectroscopy. AB - Tumor hypoxia is of considerable importance to the oncologist in selecting and optimizing cancer therapy, because hypoxia can determine the effectiveness of various therapies. The relationship between tumor hypoxia and tumor bioenergetics, assessed by 31P MR spectroscopy, is examined to determine whether 31P MR spectroscopy can be clinically useful to measure or characterize tumor hypoxia. Work with experimental tumors has suggested that several different types of hypoxia may exist and that 31P MR spectroscopy cannot be used to characterize all types. Metabolic hypoxia is the level of hypoxia that results in mitochondrial impairment in cells, and it is associated with declining cellular bioenergetic status, which can be measured by enzymatic assay of adenosine triphosphate (ATP). Because 31P MR spectroscopy is sensitive to levels of ATP, it is potentially sensitive to metabolic hypoxia in vivo and may provide a rapid and noninvasive technique for characterizing metabolic hypoxia in tumors. Radiobiologic hypoxia is the level of hypoxia that results in attenuated cell death due to radiation, because radiotoxicity is directly related to tissue levels of oxygen. Radiobiologic hypoxia of tumors thus has more impact on choice of therapy, yet the relationship between metabolic hypoxia and radiobiologic hypoxia remains to be elucidated. An analysis of published data suggests that 31P MR spectroscopy is directly sensitive to metabolic hypoxia in tumors, but it is only indirectly sensitive to radiobiologic hypoxia in tumors. Therefore, 31P MR spectroscopy may be unable to quantify the cell fraction of a tumor that has radiobiologic hypoxia. However, preliminary data suggest that MR spectroscopy may prove useful for determining the effectiveness of therapeutic interventions designed to manipulate radiobiologic hypoxia in tumors or for monitoring the kinetics of tumor reoxygenation after treatment. PMID- 1853800 TI - Broncholithiasis: CT features in 15 patients. AB - Broncholithiasis is a disorder characterized by peribronchial calcific nodal disease that either erodes into an adjacent bronchus or distorts the bronchi. The key radiologic finding is a calcified endobronchial or peribronchial lymph node. To determine the CT findings of broncholithiasis, we retrospectively reviewed the chest radiographs and CT scans of 15 patients with proved broncholithiasis. Ten patients had endobronchial nodes as proved by bronchoscopy, surgery, or lithoptysis. Broncholiths were identified on bronchoscopy in only five cases. Five patients had peribronchial nodes with associated bronchial distortion. Collimation of the CT scans varied; 1.0-cm-, 0.6-cm-, and 0.5-cm-thick sections were obtained. Three patients had both 1.0-cm- and 0.5-cm-thick sections. The calcified lymph node was identified on CT in all 15 patients. CT correctly localized six of 10 endobronchial nodes and four of five peribronchial nodes. Findings due to bronchial obstruction also were seen on CT; atelectasis (n = 11), infiltration (n = 4), bronchiectasis (n = 4), and air trapping (n = 1). An associated soft-tissue mass was not seen in any case. Difficulty in determining the relationship between lymph node and bronchus is due to volume averaging, which can be decreased by scanning thinner sections. CT can suggest the diagnosis of broncholithiasis and is useful when bronchoscopy does not show a broncholith. PMID- 1853801 TI - Noncardiogenic pulmonary edema resulting from intravascular administration of contrast material. PMID- 1853802 TI - Lobular carcinoma in situ of the breast: clinical, pathologic, and mammographic features. AB - Lobular carcinoma in situ (LCIS) was diagnosed in 165 surgical specimens (119 patients) at our institution between 1974 and 1987. LCIS was seen more often in younger women (mean age, 49 years) than other breast carcinomas were (mean age, 58 years). Sampling of a single breast revealed multifocal disease in 70% (96/138). When both breasts were sampled, bilateral foci were found in 50% (41/82). Of 165 breasts with foci of LCIS, 37% (61/165) had simultaneously occurring invasive cancers in the same breast. Direct mammographic-pathologic correlation of foci of LCIS was possible in 73 breasts (67 patients). Microcalcifications were an indication for biopsy in 49% (20/41) of breasts with a mammographic abnormality, but were a nonspecific finding often found in tissues adjacent to foci of LCIS. The mammogram was normal in 44% (32/73) of breasts with foci of LCIS. The mammograms of patients with LCIS and those from a group of age matched control subjects were compared by using a modified form of Wolfe's criteria and the percentage of fibroglandular elements. LCIS was seldom found in an N1 breast (1% vs 29%) or in a breast with less than 25% of its parenchymal area occupied by fibroglandular density (3% vs 33%). Compared with the control group, breasts with LCIS had more than 50% fibroglandular density (85% vs 45%) and a much higher frequency of the DY pattern (56% vs 36%). More fibroglandular density was seen in the LCIS group at all ages. Postmenopausally, the frequencies of the DY pattern and fibroglandular density greater than 50% in LCIS patients were nearly double those in the control group. LCIS patients have disease of the entire breast parenchyma, characterized by multifocality and bilaterality of various forms of lobular disease. Their mammograms reveal a higher rate of the DY pattern and higher percentages of fibroglandular or parenchymal density than those of age-matched controls. In LCIS patients, persistence of the DY pattern, or large amounts of fibroglandular density postmenopausally supports the concept that mammographically dense breasts are a marker for increased cancer risk in women 50 years old and older. PMID- 1853803 TI - Gadopentetate dimeglumine-enhanced chemical-shift MR imaging of the breast. AB - Standard T1-weighted MR images enhanced with gadopentetate dimeglumine show relatively minimal enhancement of breast lesions due to the high background signal from fat in the breast. Strongly enhancing lesions may become isointense relative to the fat signal and become invisible or indistinct after contrast administration. Fat-suppressed chemical-shift imaging (CSI) combined with administration of gadopentetate dimeglumine improves lesion detection and characterization in other areas of the body where a strong lipid signal is present. We evaluated this technique in the breast. Twenty patients with mammographic lesions were studied with standard unenhanced T1- and T2-weighted images and enhanced T1-weighted images, as well as with CSI before and after administration of gadopentetate dimeglumine. The series were ranked independently for border and matrix characteristics. The border was assessed for a smooth, irregular, or spiculated margin. The matrix or internal substance was evaluated for visibility and type of enhancement, homogeneous or inhomogeneous. The enhanced CSI images were superior to all other images in the depiction of border and matrix characteristics. Of 20 patients, a corresponding mass was detected on MR in 14. In two of the 14 patients, the lesion was seen only in the enhanced CSI images. Chemical-shift artifacts on enhanced T1-weighted images obscured border detail in several cases. Enhanced CSI improves visualization of breast lesions as compared with conventional MR imaging with or without enhancement. The enhanced CSI technique produces differential enhancement between glandular tissue and lesions while suppressing the signal from fat. This improves the visualization of border and matrix characteristics and depicts lesions that otherwise might be obscured. PMID- 1853804 TI - Lipid cyst: classic and atypical appearances. AB - Lipid cysts, a specific type of fat necrosis, frequently have a pathognomonic appearance on radiographs. This consists of a lucent lesion surrounded by a smooth rim that may or not be calcified. Occasionally, lipid cysts with unusual mammographic appearances are encountered. An appreciation of some of these appearances may prevent unnecessary biopsies. PMID- 1853805 TI - Zum Grunen Glas. PMID- 1853806 TI - Abdominal desmoids: CT findings in 25 patients. AB - Desmoids are histologically benign but locally aggressive fibrous tumors. Although overall they are rare lesions, they are a common manifestation of Gardner syndrome. We retrospectively reviewed clinical records and CT scans of 25 patients with abdominal desmoids. The number, location, and CT characteristics of the lesions were recorded for each patient. Tumors were solitary in 72% of patients and multiple in 28%. Fifty percent were located in the abdominal wall, 41% in the mesentery, and 9% in the retroperitoneum. More than two thirds of the lesions had well-defined borders, with the remainder displaying an infiltrative outer margin. The majority of tumors had attenuation values equal to (47%) or greater than (41%) the attenuation of muscle on contrast-enhanced CT scans. Complications attributable to the desmoid were commonly detectable on CT (hydronephrosis occurred in 36% and small-bowel obstruction in 20%). Our results detail the spectrum of CT findings and complications caused by abdominal desmoids. PMID- 1853807 TI - A versatile patriot. PMID- 1853808 TI - Biliary lithotripsy: correlation between gallbladder contractility before treatment and the success of treatment. AB - We perform biliary lithotripsy without adjuvant chemolitholytic agents, and therefore fragment clearance depends solely on the gallbladder's ability to evacuate its contents. We studied 205 patients to determine if gallbladder contractility before biliary lithotripsy is a predictor of treatment results and rate of fragment clearance. Percentage gallbladder contraction was calculated from the fractional difference in the sonographically measured gallbladder volumes before and after a fatty meal. Seventy-six patients (37%) were free of stones and fragments, and 129 patients (63%) had residual fragments at comparable follow-up intervals. Statistical analysis showed a significant difference in gallbladder contractility before biliary lithotripsy between the fragment-free group and the residual-fragment group (p = .008). Stone burden before treatment showed no significant difference between the groups (p = .074), but the number of stones was significantly less in the fragment-free group (p = .022). In the fragment-free group, a poor correlation (r = .047) was found between the percentage gallbladder contraction and the rate of fragment clearance. These data indicate that contractility of the gallbladder before treatment correlates with overall success of biliary lithotripsy but is not a predictor of the speed of fragment clearance. PMID- 1853809 TI - Diagnosis of portal vein thrombosis: value of color Doppler imaging. AB - This study was undertaken to determine the accuracy of color Doppler imaging in the diagnosis of portal vein thrombosis. Two hundred fifteen patients were studied with color Doppler imaging to determine patency of the main portal vein. Sonographic findings were confirmed in 75 patients, aged 19 to 66 years. Correlation with angiography was obtained in 13 patients, and surgical correlation was obtained in the remaining 62. Nine patients had portal vein thrombosis on the basis of these gold standards. Sonograms were classified as showing either patency or thrombosis, depending on the ability to show color flow within the main portal vein. Agreement between sonography and angiography or surgery was found in 69 patients (61 patent, eight thrombosed). One patient with a patent portal vein at sonography was found to have a thrombosed vessel at surgery, whereas five patients without portal venous flow at sonography had patent vessels at angiography (one patient) or surgery (four patients). Overall sensitivity and specificity for detection of portal vein thrombosis were 89% and 92%, with an accuracy of 92%, a false-negative rate of 0.11, a negative predictive value of 0.98, and a positive predictive value of 0.62. We postulate that the majority of errors in our study occurred in vessels that, although patent, had only sluggish flow, which could not be resolved because of technical limitations. We conclude that color Doppler imaging is a valuable screening procedure for the assessment of portal vein patency. If the sonogram shows a patent portal vein, no further studies are required. However, a lack of demonstrable flow does not always indicate thrombosis, and other imaging studies should be performed for confirmation. PMID- 1853810 TI - MR imaging of the portal venous system: value of gradient-echo imaging as an adjunct to spin-echo imaging. AB - We evaluated the use of gradient-echo (GRE) as an adjunct to spin-echo (SE) MR imaging of the portal venous system. GRE imaging was performed in 31 subjects, 15 normal volunteers and 16 patients with documented portal venous disease (15 cases) or suspected disease (one case). Eight of 16 patients had venous thrombosis, five had focal thrombus, and three had complete occlusion. Six patients had extrinsic venous compression by tumor. Of the two other patients, one had an arteriovenous fistula and the other a falsely positive angiogram, suggesting portal vein occlusion. In normal subjects, GRE scans had excellent visualization of the portal venous system with high intravascular signal compared with surrounding tissues. Nine (60%) of 15 normal subjects and three patients had an artifact consisting of a curvilinear area of decreased signal that could mimic clot. In three of five patients with focal thrombus, clot was identified on GRE but not on SE images. In all three patients with occlusion, SE and GRE images demonstrated similar findings. In five of the six patients with extrinsic venous compression by tumor, SE and GRE studies showed similar findings. Of the two patients, an arteriovenous fistula was seen on GRE MR in one, and in the other, patency of the left portal vein was seen on SE and GRE images after angiography had suggested portal vein occlusion. Collateral vessels were seen in nine of 16 patients. In five of nine cases, GRE MR demonstrated more extensive collaterals than did SE MR. In summary, GRE MR provides a useful adjunct to standard SE MR imaging. Benefits include high contrast between vascular structures and surrounding tissues, reduced motion artifact, and rapid scanning within a breath hold. PMID- 1853811 TI - Acute torsion of a wandering spleen: diagnosis by CT and duplex Doppler and color flow sonography. PMID- 1853812 TI - Gastric carcinoma in patients with Crohn disease: report of four cases. AB - An association between Crohn disease and gastric carcinoma has not been described before. However, we report four patients with documented Crohn disease in whom gastric carcinoma developed later. In three of the four patients, onset of Crohn disease occurred after the age of 40. All of the patients had nonspecific constitutional symptoms and/or complaints referable to the upper gastrointestinal tract. No clinical evidence of active Crohn disease was present. In each patient, barium examination and CT showed either a mass (two cases) or other radiologic features of malignancy (two cases). Endoscopy with biopsy was performed in three patients and findings were misleading in two patients. The possibility of an increased risk of malignancy in sites remote from inflamed bowel segments has been reported. The findings in this study suggest that patients with Crohn disease, particularly disease of late onset, may be predisposed to the development of gastric carcinoma. PMID- 1853813 TI - Diffuse stenosis of the ileum after ureteroileal interposition: radiologic pathologic correlation in two cases. PMID- 1853814 TI - Primary esophageal melanoma. PMID- 1853815 TI - Giant thoracic osteophyte causing esophageal food impaction. PMID- 1853816 TI - Retroperitoneal fibrosis. AB - Retroperitoneal fibrosis is idiopathic in two thirds of cases and is found most commonly as an isolated fibrotic plaque centered over the lower lumbar spine and entrapping one or both ureters. It has been postulated that the fibrosis in the idiopathic cases results from a hypersensitivity reaction to antigens leaking into the retroperitoneum from atheromatous plaques in the aorta or common iliac arteries. In the remaining one third of cases, causes include ergot-derivative drugs, retroperitoneal hemorrhage or urine extravasation, and a desmoplastic response to a variety of tumors. In up to 15% of cases, associated fibrotic processes are found elsewhere in the body. Although the disease is imaged best with CT or MR, neither of these techniques can be used to differentiate benign from malignant plaques. Histologically, the disease is characterized in its early stages by inflammatory cells and edema in a loose collagen network. The mature plaque is composed of dense fibrous tissue with minimal cellular infiltration. This progression is important as it influences MR signal characteristics. PMID- 1853817 TI - Color Doppler sonography in the evaluation of erectile dysfunction: patterns of temporal response to papaverine. AB - Most studies of duplex Doppler sonography for the assessment of erectile dysfunction involve determination of peak systolic velocities 5 min after intracavernosal injection of papaverine. The purpose of this study was to determine the effect of the timing of Doppler measurements of flow after papaverine injection for establishing the presence of arterial and venous abnormalities. Color Doppler sonography was performed in 75 patients for evaluation of vasculogenic impotence. After intracavernosal injection of 60 mg of papaverine, measurements of peak systolic and end-diastolic velocities were obtained in each cavernosal artery at 5-min intervals for a total of 30 min. A peak systolic velocity of less than 25 cm/sec was used as the threshold for arterial insufficiency. An end-diastolic velocity of greater than 5 cm/sec was used to predict venous incompetence. Scanning was performed for direct assessment of dorsal venous flow. Thirty patients were subsequently evaluated by cavernosometry and cavernosography. In most patients (76%), maximum response to papaverine was achieved within the first 5 min. In eight patients, significant increases in systolic velocity were seen only after 5 min. In 10 patients, significant changes in end-diastolic velocity between 5 and 30 min resulted in diagnostic reclassification. Data acquisition for 30 min significantly improved the sensitivity (95%) and specificity (83%) for the prediction of venous incompetence in patients with correlative cavernosography. Transient, early dorsal vein flow was noted in normal subjects. Persistent dorsal vein flow had an 80% sensitivity and 100% specificity for venous incompetence. Our results suggest that, when using color Doppler sonography, gathering data for 30 min may improve the prediction of vasculogenic impotence. PMID- 1853818 TI - Abnormalities of the seminal tract causing infertility: diagnosis with endorectal sonography. AB - Endorectal sonography, developed primarily for use in the diagnosis and staging of prostatic carcinoma, should be the first imaging technique used in the evaluation of an infertile man with low semen volume in whom either a hypoplastic or obstructed seminal tract is suspected. Endorectal sonography allows visualization of the seminal vesicles, which are otherwise difficult to examine. We used endorectal sonography to evaluate six young men, five of whom were being evaluated for azoospermia and infertility. One patient had no identifiable seminal vesicle on either side. Four patients had unilateral absence of the seminal vesicles. Of these four, three had a sonographically normal-appearing seminal vesicle on the contralateral side, and the fourth had an obstructed system contralaterally. The sixth patient had a hypoplastic system on the left and an obstructed system on the right. The delineation of an obstructed or agenetic seminal vesicle and seminal tract on endorectal sonography allows decisions to be made regarding treatment and prognosis. PMID- 1853819 TI - John Caffey Award paper. Avascular necrosis: early MR imaging and histologic findings in a canine model. AB - To examine the early MR and histologic changes of avascular necrosis, we surgically devascularized the distal femur of adult beagle dogs and performed short TR/short TE MR imaging and histologic examinations. MR showed increasing areas of low signal, and histologic examination showed changes of fat necrosis, inflammatory infiltrate, and fibrocytic and bony repair. These processes were divided into four stages. Stage 1 is seen in the first days after surgery and consists of homogeneous high signal on MR and only subtle histologic changes of early fat necrosis. Stage 2, seen by 7 days after surgery, shows linear low signal areas within the high-signal marrow on MR and fat necrosis and an inflammatory infiltrate on histologic sections. Stage 3, seen by 16 days after surgery, shows patchy low signal occupying more of the marrow on MR with a fibrocytic infiltrate on histologic sections. Stage 4, seen by 23 days after surgery, shows a more homogeneous low and intermediate signal on MR and histologic findings of more organized fibrocytes and the onset of new bone formation. Using this model, we have proved that MR imaging can show marrow changes as soon as 1 week after the onset of avascular necrosis. Whereas MR imaging showed a progression of increasing areas of low signal, the histologic findings seen during this time were diverse, including inflammatory infiltration (a previously unreported finding), fat necrosis, and fibrocytic and osseous repair. PMID- 1853820 TI - Preoperative evaluation of osteosarcoma: value of gadopentetate dimeglumine enhanced MR imaging. AB - Decisions regarding the surgical approach in osteosarcoma require accurate assessment of tumor extent. In order to determine whether enhancement with gadopentetate dimeglumine could add clinically significant information to that available with unenhanced MR imaging, 21 patients with osteosarcoma underwent preoperative MR imaging. T1- and T2-weighted spin-echo MR images obtained before and after administration of IV gadopentetate dimeglumine were evaluated to determine the conspicuity of marrow and soft-tissue extent of tumor, including tumor involvement of major neurovascular bundles and adjacent joints. MR results were correlated with tumor margins found at surgery. In some instances, use of gadopentetate dimeglumine obscured differentiation of tumor from normal marrow or tumor infiltration into perineurovascular fat, and tumor extension through pseudocapsule could not be differentiated from peritumoral edema after contrast administration. Contrast enhancement did assist in differentiation of intraarticular tumor from effusion; however, synovial invasion could be identified on unenhanced T1-weighted images by loss of synovial fat and cortical disruption. These results indicate that gadopentetate dimeglumine does not assist in defining tumor margins of osteosarcoma. PMID- 1853821 TI - Soft-tissue sarcoma: MR imaging vs sonography for detection of local recurrence after surgery. AB - To determine the value of MR and sonography in detecting local recurrences of soft-tissue sarcomas after surgery, 26 MR and sonographic studies performed in 21 patients were reviewed retrospectively. Recurrences were confirmed histologically in 12 (46%) of 26 studies. The MR images and sonograms were obtained within 1 month of each other. The findings were classified as recurrence, no recurrence, or indeterminate. Sonography was instrumental in guiding fine-needle aspiration biopsy of impalpable lesions. In two cases, the findings on sonography were indeterminate. In both of these cases, the sonograms had been obtained soon after surgery (at 2 and 4 months). The sensitivity and specificity in the detection of local recurrences were 83% and 93%, respectively, for MR and 100% and 79%, respectively, for sonography. These differences were not statistically significant. We conclude that MR and sonography appear to be equally useful in the detection of local recurrences of soft-tissue sarcomas, sonography can be used for routine follow-up and in guiding needle biopsies, sonography may be more difficult to interpret than MR during the early postoperative period, and MR should be used if sonography is inconclusive. PMID- 1853822 TI - Improved imaging of bone with scan equalization radiography. AB - Use of scan equalization radiography (SER) for imaging bone in the head, face, neck, and shoulder was evaluated in a clinical comparison study with conventional radiographs of randomly selected patients. Two hundred nine pairs of normal and abnormal SER images and conventional radiographs were compared by four radiologists in a side-by-side viewing situation. The radiologists compared the visibility of specific anatomic features and rated the SER images as better than, equal to, or worse than the conventional radiographs. In the evaluation of the images of the cervical spine, the radiologists much preferred the SER images 63% of the time because of slight improvement in bone detail and marked improvement in detail of the soft tissues. In the evaluation of the images of the shoulder, the radiologists preferred the SER image 58% of the time and preferred the conventional radiograph only 5% of the time (p less than .05). In the evaluation of the images of the skull, face, and mandible, the radiologists preferred the SER images 62% of the time and the conventional images 4% of the time (p less than .05). The superior image quality with the SER technique was recognized by all radiologists in the study and was the overwhelmingly preferred way of imaging the shoulder, neck, head, and face. PMID- 1853823 TI - Bacterial osteomyelitis: findings on plain radiography, CT, MR, and scintigraphy. AB - Early detection of osteomyelitis is essential if appropriate therapy is to be started before bone devitalization. Although the 99mTc-methylene diphosphonate (MDP) bone scan may signify the possibility of osteomyelitis days or weeks before osseous changes are apparent on standard radiographs, the radiographic changes may provide important diagnostic clues. The 67Ga-citrate scan augments the diagnostic value of the 99mTc-MDP scan, and the 111In-labeled WBC scan is useful for detecting abscesses. CT aids in the detection of sequestra, and MR imaging is useful in defining the extent of the inflammatory process and in distinguishing osteomyelitis from cellulitis. In this article, we review and correlate the changes of bacterial osteomyelitis shown by these imaging methods. PMID- 1853824 TI - Synthetic vs human surfactants in the treatment of respiratory distress syndrome: radiographic findings. AB - Exosurf, a synthetic surfactant, was instilled endotracheally in 49 neonates as treatment for respiratory distress syndrome. The radiologic courses of these neonates were compared with the courses of 18 neonates previously treated with human surfactant and of 18 untreated neonates. The radiologic severity of respiratory distress syndrome decreased significantly in neonates treated with Exosurf compared with that in untreated neonates. Radiologic improvement in those treated with Exosurf was slightly delayed when compared with the improvement of age-matched neonates treated with human surfactant. Otherwise no significant difference was noted between Exosurf and human surfactant in radiologic severity of respiratory distress syndrome or in the prevalence of pulmonary interstitial emphysema, pneumothorax, and bronchopulmonary dysplasia. These findings support the thesis that artificial surfactant is an acceptable substitute for surfactants of biological origin, with possible benefits of safety and ease of use. PMID- 1853825 TI - CT of the pancreas in children. AB - CT has become a frequently used imaging method for evaluating suspected pancreatic disease in children. Although the spectrum of CT findings in pancreatic disease is well documented in adults, there is a paucity of such information in children. Familiarity with CT patterns of pancreatic disease in childhood is important for diagnosis. In this essay, we illustrate the CT findings of pancreatic lesions in children. PMID- 1853826 TI - Esophageal histoplasmosis in a child with immunodeficiency with hyper-IgM. PMID- 1853827 TI - Renal tubular dysgenesis. PMID- 1853828 TI - Carotid duplex sonography: bisferious pulse contour in patients with aortic valvular disease. AB - Characteristic systolic and diastolic pulse contours occur in the carotid Doppler waveforms of patients with aortic valvular disease that have not previously been described in publications concerning carotid duplex sonography. The purpose of this study was to evaluate the presence and characterize the nature of these carotid duplex waveform abnormalities in patients with known aortic valve disease and to correlate these changes with the severity of valve dysfunction. The study group consisted of 26 patients with aortic regurgitation or combined aortic regurgitation and aortic stenosis. Duplex studies were retrospectively reviewed by two radiologists for the presence of two systolic peaks, and for the presence of diastolic reversal of flow direction. This pattern of two systolic peaks, characteristic of aortic regurgitation, is called bisferious from the Latin "twice beating." Aortic regurgitation was graded by echocardiography as mild, moderate, or severe by the cardiologists reviewing the examination. A group of 20 age-matched patients without aortic valvular disease were similarly assessed. The bisferious pattern was demonstrated in 13 (50%) of 26 patients. Five (19%) of 26 patients had significant reversal of diastolic flow. Four patients were studied both before and after aortic valve replacement. Three had bisferious wave contours preoperatively; two of these also had diastolic reversal of flow. The fourth patient had retrograde flow in diastole without systolic contour abnormality. Postoperatively, all carotid waveforms were normal. None of the duplex waveforms in the control group demonstrated characteristic systolic or diastolic abnormalities. The bisferious waveform and retrograde diastolic flow are Doppler patterns associated with aortic valvular disease. These patterns are reversible after aortic valve replacement. While echocardiography remains the study of choice in the evaluation of suspected valvular dysfunction, up to one third of patients with aortic regurgitation may not have a detectable murmur. Therefore, identifying these patterns on carotid duplex examinations may provide clinically useful information and serve as a clue to previously unsuspected cardiovascular disease. PMID- 1853829 TI - Radiologic physics instruction for diagnostic radiologists: a survey of residency programs. Committee on Training of Radiologists, American Association of Physicists in Medicine. PMID- 1853830 TI - Diaphragmatic rupture due to blunt trauma: sensitivity of plain chest radiographs. PMID- 1853831 TI - Bottle cap ingestion. PMID- 1853832 TI - Gallbladder function in patients with spinal cord injury. PMID- 1853833 TI - Primary liver lymphoma: a diagnostic dilemma. PMID- 1853834 TI - Doppler sonography in Osler-Weber-Rendu disease. PMID- 1853835 TI - Bilateral urinomas in an adult. PMID- 1853836 TI - Fallopian tube nomenclature. PMID- 1853837 TI - MR imaging of growth recovery lines in fossil vertebrae. PMID- 1853838 TI - MR of intraspinal synovial cyst: rim enhancement with gadopentetate dimeglumine. PMID- 1853839 TI - High CT attenuation values in paranasal aspergillosis. PMID- 1853840 TI - Guard for prevention of finger-stick injuries caused by stylets. PMID- 1853841 TI - The hypertriglyceridemias: risk and management. Introduction. PMID- 1853842 TI - The hypertriglyceridemias: risk and management. PMID- 1853843 TI - Postprandial hyperlipidemia. PMID- 1853844 TI - Genetic (primary) forms of hypertriglyceridemia. PMID- 1853845 TI - Acquired (secondary) forms of hypertriglyceridemia. PMID- 1853846 TI - The hypertriglyceridemias: Risk and management. Epidemiology. PMID- 1853847 TI - The hypertriglyceridemias: risk and management. Laboratory procedures. PMID- 1853848 TI - Management of hypertriglyceridemic patients. A. Treatment classifications and goals. PMID- 1853849 TI - Management of hypertriglyceridemic patients. B. Dietary management of hypertriglyceridemic patients. PMID- 1853850 TI - Management of hypertriglyceridemic patients. C. Other nonpharmacologic approaches. PMID- 1853851 TI - Management of hypertriglyceridemic patients. D. Pharmacologic management of hypertriglyceridemic patients. PMID- 1853852 TI - Pathophysiology of triglyceride-rich particles. A. Metabolism of triglyceride rich particles. PMID- 1853853 TI - Pathophysiology of triglyceride-rich particles. B. Triglyceride-rich lipoprotein cell interactions. PMID- 1853854 TI - Breast cancer and cigarette smoking: a hypothesis. AB - In many studies, cigarette smoking has been associated with a small increase in breast cancer risk. The authors evaluated the relation of smoking to breast cancer risk in two case-control studies carried out from 1982 through 1986. In Canada, 607 women with breast cancer and 1,214 controls matched on decade of age and neighborhood were interviewed at home. In the United States, 1,955 cases of breast cancer and 805 controls with other cancers were interviewed in the hospital. In both studies, breast cancer risk was associated weakly with cigarette smoking overall. The odds ratio for women who had smoked 25 or more cigarettes per day as compared with never smokers was 1.2 (95% confidence interval (CI) 0.9-1.6) in the Canadian study and 1.2 (95% Cl 0.9-1.6) in the US study. In both studies, breast cancer risk was more strongly related to commencement of smoking at a young age. Among women who smoked at least 25 cigarettes per day in the most recent year of smoking, the odds ratios for commencement before age 16 years were 1.7 (95% Cl 1.0-2.9) in the Canadian data and 1.8 (95% Cl 1.0-3.4) in the US data, and the odds ratios for commencement at even younger ages were higher. The associations were not explained by duration of smoking, by the time elapsed since commencement, or by factors associated with cigarette smoking such as alcohol consumption or oral contraceptive use. Our findings raise the hypothesis that exposure to cigarette smoke during adolescence may increase a woman's risk of breast cancer. The hypothesis has biologic plausibility: cigarette smoke contains known carcinogens, and the developing breast is especially susceptible to cancer initiation. PMID- 1853855 TI - Re: "Vasectomy and the risk of prostate cancer". PMID- 1853856 TI - Multivariate analysis of the risk of stomach cancer after ulcer surgery in an Amsterdam cohort of postgastrectomy patients. AB - Although gastric cancer incidence is decreasing in the western world, it remains an important cause of death, and there has been debate about screening persons who have undergone gastrectomy for benign ulcers. The authors analyzed risk factors for stomach cancer mortality in an Amsterdam cohort of 2,633 postgastrectomy patients, followed from their initial surgery between 1931 and 1960 until 1975, with 99.7% complete follow-up. Increased stomach cancer mortality was observed in the study population (compared with the general Dutch population) among males 25 years or more after surgery (observed/expected, 5.0; 95% confidence interval (Cl) 2.8-8.3), and among females 15-24 years postoperatively (observed/expected, 3.5; 95% Cl 1.0-9.0). A multivariate Poisson regression analysis showed that after control for age at time of surgery and calendar year of operation, the most important risk factors were time since surgery (0-4 years, relative risk (RR) = 1.0; 5-14 years, RR = 4.1, 95% Cl 0.93 18.5; 15-24 years, RR = 9.4, 95% Cl 2.1-42.3; and 25-46 years, RR = 55.6, 95% Cl 11.7-265.4) and ulcer location (gastric versus duodenal ulcer, RR = 2.6, 95% Cl 1.4-4.8). Surveillance for postgastrectomy cancer could be considered 15-25 years after a patient undergoes surgery for gastric ulcer disease. PMID- 1853857 TI - Antigenic stimulation and the occurrence of chronic lymphocytic leukemia. AB - Data from a population-based case-control study of chronic lymphocytic leukemia were analyzed to assess the possible etiologic role of chronic antigenic stimulation. The study, conducted in four geographic areas of the United States (the metropolitan areas surrounding Seattle, Washington, Salt Lake City, Utah, Detroit, Michigan, and Atlanta, Georgia) sought to identify all incident cases (n = 430) among residents diagnosed between July 1, 1977 and December 31, 1981. The responses of these cases to questions about possible sources of antigenic stimulation were compared with the responses of controls selected from the populations of these areas. Little difference between cases and controls was present for a history of most forms of viral and bacterial infection and for a history of allergies or allergy treatment. However, a relation was observed with antecedent syphilis infection (odds ratio (OR) = 5.0, 95% confidence interval (Cl) 2.0-12.9). Associations of smaller magnitude were observed with a history of tuberculosis (OR = 1.9, 95% Cl 1.0-3.7) and of urinary tract infection (OR = 1.4, 95% Cl 1.1-1.9). Overall, however, the authors found little evidence of a relation between chronic antigenic stimulation and the occurrence of chronic lymphocytic leukemia. Nonetheless, because the measure of prior antigenic stimulation was restricted to that obtained through interviews and undoubtedly was an insensitive one, these negative results should not be interpreted as ruling out antigenic stimulation as a possible cause of some cases of chronic lymphocytic leukemia. PMID- 1853858 TI - Factors associated with paradoxical survival at higher blood pressures in the very old. AB - Paradoxically greater survival for persons aged 85 years and older with higher blood pressures has been reported in a Finnish population study (Br Med J 1988;296:887-9). In a previous report, the authors demonstrated improved 10-year survival with increasing diastolic blood pressure in men (but not in women) aged 75 years and older in the Rancho Bernardo Chronic Disease Study (Br Med J 1989;298:1356-7). However, few of the covariates which could potentially explain this effect were obtained at the visit used in that analysis. In an effort to confirm these reports of paradoxical survival and to explore possible reasons for them, the authors analyzed all-cause and cardiovascular mortality in 795 men and women aged 75-96 years (mean, 80.6), evaluated in 1984-1987 and followed prospectively for an average of 3 years after that comprehensive examination. Of 63 deaths, 48 (76%) were in men; 43 (68%) of all deaths were cardiovascular. Kaplan-Meier survival analyses showed a significant trend for improved survival with increasing diastolic pressure in men aged 80 years and older versus all cause mortality (chi 2 p less than or equal to 0.01), and cardiovascular mortality (chi 2 p less than or equal to 0.00). These trends were not evident in men aged less than 80 years or in women in either age group. Results were not explained by differences in the use of antihypertensive medication, pulse pressure, history of hypertension, history of coronary heart disease, isolated systolic hypertension, interval change in diastolic pressure (over an average of 12 years), or by cholesterol, triglycerides, fasting plasma glucose, smoking, or body mass index. Thus, the paradoxical relation of improved all-cause and cardiovascular survival in men aged 80 years or older with higher diastolic pressure is not explained by a wide range of biologic and historical factors. PMID- 1853859 TI - The impact of the Guidelines for a Healthy Diet of The Netherlands Nutrition Council on total and high density lipoprotein cholesterol in hypercholesterolemic free-living men. AB - To study the impact of dietary intervention on the plasma total and high density lipoprotein cholesterol (HDL cholesterol) levels in hypercholesterolemic men, the authors selected 80 male participants in a monitoring risk factor project carried out in Amsterdam, The Netherlands. These men had plasma total cholesterol levels of between 6.5 and 10.0 mmol/liter (between 251 and 387 mg/dl) and were randomly assigned to either the intervention (n = 39) or the control (n = 41) group. At the start of the intervention period, after 5 weeks, and after 26 weeks, both the intervention and the control groups were examined. This examination consisted of a measurement of height, weight, plasma total and HDL cholesterol, and a dietary interview. The intervention program consisted of a personalized dietary advice to the respondent, based on the report of the Netherlands Nutrition Council. The study took place between September 1987 and November 1988. Because of this intervention program, the plasma total and HDL cholesterol levels decreased. The difference in change in plasma total cholesterol between the intervention and control groups was 0.47 mmol/liter (18 mg/dl) after 5 weeks and 0.30 mmol/liter (12 mg/dl) after 26 weeks. For HDL cholesterol, a significant difference in change after 5 weeks disappeared after 26 weeks. The public health implications of the decrease in plasma total cholesterol are discussed. PMID- 1853860 TI - A co-twin control study of the effects of the Vietnam War on the self-reported physical health of veterans. AB - This study examines the impact of military service on 13 categories of self reported physical health problems by using a sample of 2,260 American male-male monozygotic twin pairs who served on active duty during the Vietnam War. Data were collected in 1987 by using mail and/or telephone interviews. Twins who served in Southeast Asia reported an increased prevalence of currently having hearing problems (odds ratio (OR) = 1.9, 95% confidence interval (Cl) 1.3-2.7) and persistent skin conditions (OR = 2.1, 95% Cl 1.4-3.2). Odds ratios for these health problems increased with increasing combat exposure and could not be explained by confounding due to posttraumatic stress disorder or demographic or military service factors. Significantly increased odds ratios were also demonstrated for ever having hearing problems (OR = 1.8, 95% Cl 1.3-2.5), ever having persistent skin conditions (OR = 2.1, 95% Cl 1.5-3.0), and having been hospitalized for stomach conditions (OR = 2.6, 95% Cl 1.4-4.9). Marginally increased odds ratios were demonstrated for ever having stomach conditions (OR = 1.4, 95% Cl 1.0-1.9) and urinary conditions (OR = 1.5, 95% Cl 1.0-2.1). Service in Southeast Asia was not associated with any of the remaining categories of physical health problems. Thus, although the past health of veterans who served in Southeast Asia may have been somewhat worse than that of their siblings who did not serve in southeast Asia, no major differences in current health are detected. PMID- 1853861 TI - A population-based study of injuries in inner-city women. AB - Although injuries are the number one cause of death for women under age 45 years in the United States, very little is known about nonfatal injuries to women, particularly those from urban, black communities. The Philadelphia Injury Prevention Program is a surveillance system of fatal and nonfatal injuries in a poor, urban, black community in western Philadelphia, Pennsylvania. Nearly 10% of the estimated population of 31,032 women aged 15 years and older suffered an injury resulting in an emergency room visit or death during the 1-year study period from March 1, 1987 through February 29, 1988. The major causes of injury were falls (25.1 per 1,000 women), violence (20.8 per 1,000 women), and motor vehicle incidents (16.8 per 1,000 women). Violence was the leading cause of injury for women aged 15-44 years and the most common cause of injuries among women with two or more injuries during the 1-year period. Injury rates were highest for women aged 25-34 years (157.1 per 1,000 women); nearly 16% of the population in this age group suffered an injury resulting in an emergency room visit or death during the 1-year study period. Rates declined with advancing age for each injury type except for falls; which were most common in young women aged 25-34 years (28.4 per 1,000 women) and in the aged 65 years and older (29.0 per 1,000 women). We conclude that in his population, injuries to young women appear to be a major public health problem. More work is needed to understand the nature of injuries occurring to young women in urban communities. PMID- 1853862 TI - Completeness of the discharge diagnoses as a measure of birth defects recorded in the hospital birth record. AB - Licensed hospitals usually maintain a discharge diagnoses index, which provides an inexpensive tool for the surveillance of birth defects diagnosed shortly after birth. Government agencies in several states routinely use discharge diagnoses for this purpose. To evaluate the completeness of the discharge diagnoses, the authors compared birth defects noted in the discharge diagnoses with those noted anywhere in the hospital birth record in a cohort of 3,421 infants born to US Army veterans from 1966 to 1986. In this cohort, 237 birth defect cases were documented in hospital birth records, and 49% of those cases were missed in the discharge diagnoses (28% of major defect cases and 66% of minor defect cases). The extent of missed defects varied greatly by organ system and by specific defect. Significant predictors of a missed defect were the presence of multiple defects, female sex, and western region of birth. The underascertainment of defects in the discharge diagnoses should be considered in the development and operation of surveillance systems using this source of data. PMID- 1853863 TI - Plasma lipids and gallbladder disease. AB - The relation between plasma lipids and gallbladder disease was examined by using data collected between 1984 and 1987 from 1,303 Rancho Bernardo, California, women aged 50 years and older. In univariate analyses and after adjustment for age and body mass index, high density lipoprotein cholesterol (HDL cholesterol) and low density lipoprotein cholesterol (LDL cholesterol) were inversely related and triglyceride level was positively related to gallbladder disease. However, using multiple logistic regression, only LDL cholesterol, triglycerides, age, and body mass index were significantly related to a history of gallbladder disease, whereas HDL cholesterol was no longer associated with gallbladder disease. The risk of gallbladder disease increased with greater age, body mass index, and triglyceride level, but decreased with increasing LDL cholesterol level. Total amount of alcohol consumed per week, number of cigarettes smoked per day, and current estrogen use were not significantly associated with gallbladder disease. The relation of HDL cholesterol and LDL cholesterol to the risk of gallbladder disease requires further investigation. PMID- 1853864 TI - Anti-tick saliva antibody: a biologic marker of tick exposure that is a risk factor for Lyme disease seropositivity. AB - Anti-tick saliva antibody (ATSA) has potential as a biologic marker of exposure to tick bites. In 1989, we conducted a cross-sectional study of 304 outdoor workers in Monmouth County, New Jersey, to evaluate associations between self reported tick exposure, ATSA status, and Lyme disease antibody status. ATSA levels 1) were correlated with an index of tick exposure on the basis of three self-reported measures of tick exposure and outdoor hours worked per week (p = 0.01); 2) were consistently higher in pet owners compared with persons without pets (p = 0.03); and 3) when examined by duration since last tick bite, peaked at 3-5 weeks after tick bite and then declined (p = 0.06). ATSA levels dichotomized at the 75th percentile (approximately two standard deviations above the mean ATSA optical density of 25 subjects who denied recent tick exposure) were associated with self-reported tick exposure: adjusted odds ratios for high ATSA levels were 4.2 (95% confidence interval (CI) 0.9-18.9) for moderate (versus none) tick exposure and 5.8 (95% CI 1.2-27.2) for high (versus none) tick exposure. Finally, high ATSA levels were associated with Lyme disease seropositivity, with an adjusted odds ratio of 3.2 (95% CI 1.3-7.6). The data suggest that ATSA is a biologic marker of tick exposure that is a risk factor for Lyme disease seropositivity. PMID- 1853866 TI - Pharmacy in Lithuania and the development of a sister-school relationship between colleges of pharmacy. PMID- 1853865 TI - Sampling elderly in the community: a comparison of commercial telemarketing lists and random digit dialing techniques for assessing health behaviors and health status. AB - A study of health behaviors in four communities in the western United States in 1988 provided the opportunity to compare two methods of sampling elderly respondents for a telephone interview. The Polk telemarketing lists were used to identify 1,407 respondents aged 65 years and older in four communities, where 253 respondents in the same age group were also identified by the method of random digit dialing. Individuals identified from the Polk lists received a letter prior to the initial telephone contact. The overall response rate was 49.3% for random digit dialing and 57.3% for the Polk lists. On the average, the identification of one elderly respondent using the Polk lists required about 20-25% as much interviewer time per subject identified as was required by the random digit dialing method. The elderly identified by the Polk lists were significantly older than those identified by random digit dialing, and the proportions of the Polk sample who were married, white, or had an income of greater than $10,000 were slightly higher than those of the random digit dialing sample. Among 40 variables measuring various health behaviors, indicators of health status, and participation in health-related programs and classes, only three differed significantly between the two samples. The authors conclude that sampling from commercial telemarketing lists was an efficient method of identifying elderly respondents and that in these four communities, the estimates of health behaviors and health status were comparable with those obtained by random digit dialing techniques. PMID- 1853867 TI - Adverse events involved in 3.7% of hospitalizations in New York in 1984, study finds. PMID- 1853868 TI - American Nurses Association adopts position on polypharmacy. PMID- 1853869 TI - Frequency of JCAHO-mandated medication inspections. PMID- 1853870 TI - Transforming policies and procedures from burden to boon. PMID- 1853872 TI - Pharmacy needs a computer-rating group. PMID- 1853871 TI - Personal shampoos and safety considerations. PMID- 1853873 TI - I, too, am an HIV-positive pharmacist. PMID- 1853874 TI - Affordability of cimetidine. PMID- 1853875 TI - Antineoplastic admixtures. PMID- 1853876 TI - Gaining external support for pharmacy's new mission. PMID- 1853877 TI - Tracking manuscripts and reviewers electronically. PMID- 1853878 TI - Use of bar codes in inpatient drug distribution. AB - The development and operation of a prototype inpatient drug distribution system that uses bar codes is described, and the impact of bar coding on the cassette filling and verification process is summarized. A prototype pharmacy dispensing site was created to function in parallel with an existing satellite dispensing site that served 78 general medical-care beds. Supplemental labels encoded with an 11-digit unique product identification number, a 5-digit expiration date, and a 6-character lot number were generated and affixed to all unit dose packages dispensed from the prototype pharmacy site. The unit doses were labeled with Code 49 symbology; each label measured 0.8 x 1.25 inches. Each patient cassette was labeled using Code 39 symbology. A cost-benefit model was developed, and the two dispensing systems were compared with respect to (1) time to fill patient cassettes, (2) time to verify patient cassettes, (3) time to process patient charges and credits, (4) time to correct dispensing errors, (5) accuracy of the cassette-filling process, and (6) accuracy of the cassette verification process. Bar-code dispensing and verification saved 1.52 seconds per dose. Additionally, the cassette verification function was shifted from pharmacists to technicians. Estimated per-dose cost of the bar-code system was 2.73 cents. A measurable improvement in the accuracy of filling patient cassettes was documented. The feasibility of using bar codes in unit dose dispensing was demonstrated, and the prototype system was shown to produce cost efficiencies and patient-care benefits. PMID- 1853879 TI - National survey of pharmaceutical services in psychiatric hospitals. AB - The results of a summer 1989 nationwide mail survey of psychiatric hospital pharmaceutical services are reported and discussed. A simple random sample of 200 hospitals was selected from 600 psychiatric hospitals registered by the American Hospital Association. Questionnaires were mailed to the director of pharmacy at each institution. Usable responses were received from 114 hospitals, for a net response rate of 57%. Responses were categorized by hospital size, ownership status, geographic region, and average length of stay. Substantial differences were noted between government and nongovernment hospitals in the number and types of pharmaceutical services provided, as well as in the manner in which services are provided. Non-government hospitals generally appeared to offer more progressive pharmaceutical services. Psychiatric hospitals in western states appeared to offer more advanced clinical pharmacy services than institutions in other geographic areas. The survey established baseline data on the nature and extent of both clinical and distributive services in psychiatric hospital pharmacy departments. PMID- 1853880 TI - National survey of state psychiatric hospital pharmacies. AB - The results of a winter 1990 nationwide mail survey of pharmaceutical services provided in state psychiatric hospitals are reported and discussed. The survey universe consisted of all 207 state psychiatric hospitals registered by the American Hospital Association. Private and federal and other government-operated psychiatric hospitals were not included. Questionnaires were mailed to the director of pharmacy at each institution. Two questionnaires were not deliverable. There were 117 usable replies, for a net response rate of 57.1%. Compared with community hospitals, state psychiatric hospitals had pharmacy departments that were open fewer hours per week, occupied more floor space, were less likely to have a complete unit dose distribution system and i.v. admixture program, had lower inventory turnover rates, and had fewer full-time positions. About 28% of the respondents employed pharmacists who spent at least two thirds of their time providing clinical services. Differences in the provision of pharmaceutical services between state psychiatric hospitals and community hospitals may be due in part to the fact that most of the former are long-term care institutions rendering a specific class of therapies. PMID- 1853881 TI - Instructions provided by manufacturers for proper use of nonprescription ophthalmic drops. PMID- 1853882 TI - Stability of cefadroxil in reconstituted suspension under refrigeration and at room temperature. PMID- 1853883 TI - Hydrops fetalis in the McKusick-Kaufman syndrome: a case report. AB - McKusick-Kaufman syndrome is an autosomal recessive multiple malformation syndrome characterized by hydrometrocolpos and polydactyly. We report on a patient with McKusick-Kaufman syndrome and severe hydrops. This case illustrates the necessity of genetic evaluations for all patients with unexplained hydrops. PMID- 1853884 TI - Correlation between sexual abuse and somatization in women with somatic and nonsomatic chronic pelvic pain. AB - After a comprehensive clinical and psychological evaluation, 99 women with pelvic pain of at least 6 months' duration and normal findings at laparoscopy were divided into two groups, including 47 women with probable somatic causes of pain (group 1) and 52 women without identifiable somatic abnormality (group 2). Women without identifiable somatic abnormality (group 2) were younger, had higher mean somatization scores, and reported an earlier mean age at first intercourse, a higher number of total sexual partners, and a higher prevalence of sexual abuse before the age of 20. Within group 2 (nonsomatic pain) but not within group 1, mean somatization scores were significantly higher among women with a history of sexual abuse than among women with a negative history. When analyzed as risks for nonsomatic pelvic pain, the positive predictive value of both a history of sexual abuse and a high somatization score was 78% (relative risk compared with that of women with zero or one risk factor, 2.1; p less than 0.0001). These data suggest that the psychosocial profile of women with nonsomatic pelvic pain differs from that of women with somatic pelvic pain and that previous sexual abuse is a significant predisposing risk for somatization and non-somatic chronic pelvic pain. PMID- 1853885 TI - Predictive value of early embryonic cardiac activity for pregnancy outcome. AB - The biologic variation of the embryonic heart rate was investigated by transvaginal ultrasonography during the first trimester of normal (n = 141) and abnormal (n = 29) pregnancies, and the predictive value of a repeatedly diagnosed slow heart rate for pregnancy outcome was determined. The mean heart rate increased from 82 +/- 10.3 beats/min at 5 weeks' gestation to 156 +/- 9.6 beats/min at 9 weeks. A single observation of an abnormally slow heart rate did not necessarily predict subsequent embryonic death. However, a continued decline in embryonic heart activity, observed within a few days' interval, was always associated with a first-trimester abortion. PMID- 1853886 TI - Cesarean section by local anesthesia in patients with familial dysautonomia. AB - We describe a 29-year-old patient with familial dysautonomia who underwent cesarean section because of severe intrauterine fetal growth retardation. The surgery was done after induction of local anesthesia to avoid the critical and sometimes fatal complications of general anesthesia known in patients with familial dysautonomia. Surgery was uneventful and almost painless. The postoperative period was without complications. Induction of local anesthesia for cesarean section may constitute a suitable alternative in patients with familial dysautonomia. PMID- 1853887 TI - Endothelin production by amnion and its regulation by cytokines. AB - Cells derived from human amnion, an avascular tissue, produced significant amounts of endothelin 1 and 2, although the rate of biosynthesis was approximately one tenth of that of human umbilical vein endothelial cells. Endothelin 1 and 2 was not produced in measurable amounts by cells derived from chorion laeve or decidua. Production of endothelin 1 and 2 by amnion cells was increased by treatment with the cytokines interleukin-1 beta, tumor necrosis factor, and interleukin-6. The biosynthesis of endothelin 1 and 2 by an avascular tissue is suggestive of a wider role for endothelins than has been recognized. PMID- 1853888 TI - Uterine and fetal Doppler flow changes after intravaginal prostaglandin E2 therapy for cervical ripening. AB - Nineteen patients received prostaglandin E2 as a 2.5 mg gel (seven cases), 3.3 mg chip (five cases), or 10 mg controlled-release pessary (seven cases) for preinduction cervical ripening. Blood flow velocities did not change significantly for the uterine arcuate artery, fetal aorta, and umbilical artery circulations after any of the treatments. In no case did systolic/diastolic ratios consistently elevate above baseline values. PMID- 1853889 TI - Does intensive glycemic control in diabetic pregnancies result in normalization of other metabolic fuels? AB - Intensive treatment of insulin-dependent diabetes mellitus during pregnancy often normalizes plasma glucose levels. However, it is unclear whether this adversely affects other metabolic fuels that are essential to normal fetal growth and development. Metabolic studies were conducted after the subjects ingested a standardized mixed meal during each trimester in 7 normal and 15 insulin dependent diabetic pregnant women. The latter were treated with continuous subcutaneous insulin infusion or multiple injections, which were adjusted to achieve strict glucose control throughout pregnancy. Insulin, alanine, branched chain amino acids, triglycerides, free fatty acids, and ketones were measured every 15 to 30 minutes before a standardized breakfast and for 150 minutes after the breakfast. Patients with insulin-dependent diabetes mellitus were studied while they received their unusual insulin dosages. Fasting glucose levels (87 +/- 7 mg/dl) and glucose levels 150 minutes after the meal (112 +/- 11 mg/dl) were near normal. However, normoglycemia was achieved at the expense of increased plasma insulin levels (area under insulin response curves, p less than 0.01, vs nondiabetic curves). Nevertheless, fasting and post-prandial plasma branched chain amino acids, alanine, and free fatty acids were similar in both groups. Fasting cholesterol, triglyceride, and ketone levels were also normalized. We conclude that normalization of circulating amino acids and lipids in conjunction with correction of hyperglycemia may contribute to favorable outcomes in infants of intensively treated diabetic mothers. PMID- 1853890 TI - The enhanced production of placental interleukin-1 during labor and intrauterine infection. AB - The purpose of this study was to determine the effect of labor and chorioamnionitis in interleukin-1 production by human placenta. We studied the activity of the placenta to produce interleukin-1 with an enzyme immunoassay by culturing tissue blocks. The placental tissue obtained after labor produced a larger amount of interleukin-1 than placental tissue obtained before labor. All the placental tissues produced more interleukin-1 beta than interleukin-1 alpha. The placentas with labor and chorioamnionitis produced about seventeenfold more interleukin-1 than placentas with labor only. We immunohistochemically identified interleukin-1--producing cells in the placenta and found that syncytiotrophoblasts produced both interleukin-1 alpha and interleukin-1 beta, while Hofbauer cells produced only interleukin-1 beta. In vitro analysis of the trophoblast activities to produce interleukin-1 revealed that microbial byproducts enhanced interleukin-1 production, possibly inducing accumulation of interleukin-1 receptor-positive cells at the sites of inflammation. In addition to stimulation of prostaglandin biosynthesis and labor, the placental interleukin 1 may act as an inflammatory mediator, leading to systemic and local changes at fetomaternal interface and activating fetomaternal immune systems against intrauterine infection. PMID- 1853891 TI - Arterial blood flow velocity waveforms of the pelvis and lower extremities in normal and growth-retarded fetuses. AB - Serial measurements of femoral artery flow velocity waveforms were made at specified intervals of 3 to 4 weeks from 15 to 20 weeks of gestational age to 35 weeks and 1- to 3-week intervals thereafter until delivery in 12 normal fetuses (group 1A) with pulsed Doppler ultrasonography. The pulsatility index of the femoral artery increased linearly with advancing gestation in all 12 fetuses; this was associated with reverse diastolic flow velocity waveforms. In 30 other normal fetuses (group 1B) whose gestational ages ranged between 16 and 38 weeks (mean +/- SD, 29.5 +/- 5.6 weeks), the femoral artery flow velocity waveforms were analyzed with the external iliac artery, internal iliac artery, and umbilical artery waveforms. No significant difference was observed between the pulsatility index of the external iliac artery and that of the femoral artery (mean +/- SD, 3.7 +/- 1.1 vs 3.7 +/- 1.1). The pulsatility index of the internal iliac artery was significantly higher than that observed in the umbilical artery (mean +/- SD, 1.27 +/- 0.28 vs 1.12 +/- 0.23). The femoral and umbilical artery velocity waveforms also were determined in 20 fetuses with intrauterine growth retardation (group 2), whose gestational ages ranged between 24 and 36 weeks (mean +/- SD, 31 +/- 3.4 weeks). Abnormal femoral artery pulsatility index was recorded in two fetuses who died. Absent or reverse flow of the umbilical artery was recorded in 10 fetuses; four of them died, and four others manifested fetal distress or required admission to the neonatal intensive care unit or both. These preliminary data suggest that the femoral artery pulsatility index cannot be used as an indicator of adverse fetal outcome, whereas absent or reverse flow of the umbilical artery seems to be better correlated with adverse fetal outcome. PMID- 1853892 TI - Double jeopardy: twin infant mortality in the United States, 1983 and 1984. AB - The United States Linked Birth/Infant Death Data Sets: 1983 and 1984 Birth Cohorts from the National Center for Health Statistics were used to identify maternal and infant characteristics related to twin infant mortality; 41,554 white and 10,062 black live-born matched twin pairs were evaluated. Twin birth weight distribution was skewed with 48% of white and 63% of black twins born weighing less than 2500 gm. Overall infant mortality rates were 47.1 and 79.3 deaths per 1000 live births for white and black twins, respectively (five times the rates for singletons). Three fourths of deaths were among twins weighing less than 1500 gm. White like-gender twins had about twice the risk of both twins dying compared with unlike-gender twins. Likewise, white twin pairs with greater than 25% birth weight disparity had a 40% to 80% increased risk of both twins dying, compared with twins whose weights were within 10% of each other. Twins born to high-risk women (on the basis of demographic factors) were twice as likely to die as twins born to low-risk women. Thus strategies to decrease twin infant mortality must address both maternal and infant risk factors. PMID- 1853893 TI - The influence of contamination of culture medium with hepatitis B virus on the outcome of in vitro fertilization pregnancies. AB - Heat-inactivated human serum is added to the culture medium used for in vitro fertilization and other forms of assisted conception. Because one batch of pooled serum contained hepatitis B virus, an epidemic occurred among women participating in the treatment program. Seventy-nine women had serologic proof of hepatitis B infection. This incident gave the opportunity to study the effect of hepatitis B virus on pregnancy outcome and the newborn. The situation is unique because the preimplantation embryo was exposed to hepatitis B virus or the pregnancy was complicated by a (sub)clinical infection. Twenty-four women were or became pregnant while having an acute hepatitis B infection. Five pregnancies ended in abortion. The remaining 19 pregnancies ended in the birth of 24 children. No evidence for any harmful effect of exposure to hepatitis B virus in the embryonic or fetal period on the newborn could be found. PMID- 1853894 TI - The effect of the inhibition of prostaglandin synthesis on renal blood flow in fetal sheep. AB - Treatment with prostaglandin synthesis inhibitors has been associated with oligohydramnios in the fetus. The presumed mechanism is a reduction in fetal renal blood flow. We examined the effect of meclofenamate administration on renal blood flow in chronically catheterized fetal sheep during normoxia and during moderate and severe hypoxia. Ten fetal sheep were made hypoxic twice at least 4 days after surgery: once in the presence and once in the absence of meclofenamate infusion. Renal blood flow and combined ventricular output were measured with radioactive microspheres. Prostaglandin synthesis blockade with meclofenamate caused no significant change in blood pressure, combined ventricular output, renal blood flow, or renal vascular resistance in either the normoxic or hypoxic animals. These data challenge the contention that prostaglandin activity protects the renal vascular bed of the fetus from vasoconstriction during hypoxia and they also do not support the hypothesis that prostaglandin synthesis inhibition causes oligohydramnios through reduction of fetal renal blood flow. PMID- 1853895 TI - Isolation and purification of microvascular endothelium from human decidual tissue in the late phase of pregnancy. AB - Normal pregnancy demands significant structural and physiologic adaptations of the uterine microvasculature, to facilitate adequate placentation. In pregnancies complicated by pregnancy-associated hypertension (preeclampsia), this process is defective, resulting in a high incidence of intrauterine growth retardation. The microvascular endothelium, a focal point for both initiation and inhibition of coagulation and control of vascular tone, may well contribute to development and aggravation of these abnormalities. We describe a method for isolation, purification, and culture of human decidual endothelial cells from biopsies performed at the time of cesarean section. The separation procedure is technically simple, requires only a small piece of tissue, and takes approximately 2 hours to perform. Some of the unique features of these cells in culture are outlined. This technique will permit the close examination of various aspects of the function of these cells in normal pregnancy, and their comparison with cells from pregnancies complicated by hypertension. PMID- 1853896 TI - Subserosal adenomyosis: a possible variant of pelvic endometriosis. AB - A total of 128 patients with adenomyosis were examined clinically and histologically to investigate the pathogenesis of subserosal adenomyosis. In this study 15 (11.7%) cases were classified as subserosal adenomyosis on the basis of localization of heterotopic endometrial tissues that consisted of glands and stroma. These were subclinical and incidental. The uterus was not enlarged in this type of adenomyosis. Distribution of the ectopic tissues and the patients' mean age at the time of the hysterectomy suggest that subserosal adenomyosis may develop as a variant of pelvic endometriosis. PMID- 1853897 TI - Histologic study of endometriosis and examination of lymphatic drainage in and from the uterus. AB - Histologic study of endometriosis and investigation of lymphatic drainage in and out of the uterus were conducted to obtain more information on the histogenesis of endometriosis. Endometriosis is a disease originating from the normal endometrium, specifically from its basal layer. Internal endometriosis (adenomyosis) is caused mainly by direct invasion of the endometrium into the spaces located in the connective tissue of the muscle layer. Serous and ovarian types of endometriosis are frequently found together with adenomyosis. Endometrial fragments in vessels are detected in 4.5% of cases of endometriosis. Observation of serial sections proved that serous endometriosis is caused mainly by continuous or semicontinuous invasion of the tunica muscularis spaces primarily from adenomyosis lesions and partly from the endometrium. Confirmation of lymph flow into the ovary from the uterine body strongly suggests that ovarian endometriosis arises as a consequence of vascular (lymphatic) transport of endometrial fragments from adenomyosis lesions, serous endometriosis lesions, or the endometrium. PMID- 1853898 TI - Peritoneal endometriosis: endometrial tissue implantation as its primary etiologic mechanism. AB - The mechanisms involved in primary implantation of pelvic endometriosis were investigated in women undergoing laparoscopy as part of an infertility evaluation. Among the women with a diagnosis of endometriosis, those with no observed lesions in the ovaries and no adhesions in the pelvic cavity were classified as being in stage I. These women were further subdivided into two groups: the stage Ia group in which implants were found in one area (25 women) and the stage Ib group in which implants were found in two or more areas (29 women). In both groups the most frequent site was the uterosacral ligaments followed by the posterior uterine serosa, the posterior cul-de-sac, and the posterior broad ligaments in that order. Regardless of the position of the uterus, endometriosis was found significantly more frequently in the posterior compartment. The finding that the most frequent implants on the uterosacral ligaments were near the tubal ostium and, in the stage Ia group, the absence of implants on the anterior uterine serosa but a 33% frequency on the posterior uterine serosa, which is more frequently exposed to menstrual blood, suggest that implantation of endometriosis is the result of retrograde menstruation. However, the possibility that metaplasia of the serosal epithelium is stimulated by menstrual blood cannot be ruled out, inasmuch as the process of implantation in the peritoneum has not yet been proved. PMID- 1853899 TI - A reappraisal of the coelomic metaplasia theory by reviewing endometriosis occurring in unusual sites and instances. AB - Endometriosis occurring in unusual sites and instances was reviewed for the purpose of exploring the pathogenesis of the disease. Endometriosis is frequently observed in the pelves of menstruating women. It occurs in teenagers even before menarche, in women who have never menstruated, and in postmenopausal women. It affects not only the pelvic organs but also the right-sided thoracic organs and rarely the extremities. It occurs in men who are castrated and treated with estrogen. The affected sites in both common and uncommon endometriosis include cells arising from the coelomic membrane and sites exposed to metaplasia-inducing substances such as estrogen and unknown factors liberated from the degenerating endometrium. This appears to strengthen the coelomic metaplasia theory, although additional basic and experimental data must still be accumulated to confirm this theory. PMID- 1853900 TI - Secondary mullerian system and endometriosis. AB - The pathogenesis of endometriosis is controversial. The two principal histogenetic theories are (1) metastases of endometrial tissues to an ectopic location (metastatic theory) and (2) metaplastic development of endometrial tissue at the ectopic site (metaplastic theory). Studies on the development of the coelomic cavity and the mullerian duct, as well as expression of CA 125 during the fetal period and in the adult, strongly suggest that coelomic epithelium-related tissues and mullerian-derived epithelia of the adult have a shared embryologic ancestry. Many manifestations of mullerian-directed metaplasia suggest that tissues derived from the coelomic epithelium and its accompanying mesenchymal cells, referred to as the "secondary mullerian system," have the potentiality to differentiate into mullerian-directed epithelium and stroma. This metaplastic potentiality of the secondary mullerian system constitutes a basic concept in the pathogenesis of endometriosis. PMID- 1853901 TI - Ultrastructural study of glandular epithelium in adenomyosis in comparison with those of proliferative endometrium and well-differentiated endometrial cancer. AB - Adenomyotic glandular tissue from five patients underwent electron microscopic investigation to observe its ultrastructural characteristics. The adenomyotic epithelium was compared with that of proliferative normal epithelium (two patients) and well-differentiated endometrial adenocarcinoma (two patients). The results revealed that morphologically the adenomyotic glandular epithelium is somewhat less differentiated than proliferative endometrium and that its cytoplasmic organelles have some similarities with those of endometrial cancer. Whether these similarities predispose the adenomyotic glandular tissue to malignant degeneration remains to be elucidated. PMID- 1853902 TI - Relationship between the onset of dysmenorrhea and histologic findings in adenomyosis. AB - An attempt was made to evaluate the relationship between histologic findings of adenomyosis and onset of dysmenorrhea. Thirty-four cases of histologically diagnosed adenomyosis were investigated in this study. One large sample cut along the longitudinal axis was made and examined to evaluate the histologic parameters and CA 125 levels. Dysmenorrhea was classified into grade I (absent or mild) and grade II (severe). Localization of adenomyosis was divided into type I, adenomyosis continuous from the surface endometrium (29 cases), and type II, adenomyosis present on the serous side of the uterus and not continuous from the surface endometrium (five cases). We made type I adenomyosis, which included 13 cases of grade I and 16 cases of grade II, the focus of our investigation. The parameters that correlated with dysmenorrhea were the number of islands of adenomyosis and glands, distance of invasion, relative rate of invasion, and CA 125 levels. The differences between grades I and II were apparent in the frequency distribution tables, with dysmenorrhea occurring at invasion rates of 80% and greater. PMID- 1853903 TI - Twin delivery: influence of the presentation and method of delivery on the second twin. AB - To ascertain the perinatal mortality and morbidity in the second twin as related to its presentation and method of delivery, we reviewed the data on 578 sets of twins delivered from 1980 to 1987 and included 397 sets in whom both twins were greater than or equal to 1000 gm, without lethal anomalies, and in whom the first twin presented as a vertex. The perinatal outcome comparing twin A (all vertex) with twin B (vertex or nonvertex) with cesarean section or vaginal delivery was analyzed. No statistically significant difference in perinatal mortality or morbidity was found in comparing the nonvertex second twin delivered vaginally or by cesarean section. The one perinatal death and significant perinatal morbidity occurred in infants weighing less than 1500 gm or at less than 32 weeks' gestational age. It is concluded that vaginal delivery, irrespective of the position of the second twin, is valid in selected cases as long as fetal weight is greater than 1500 gm and the gestational age is greater than or equal to 32 weeks. PMID- 1853904 TI - Animal model of uterine adenomyosis: is prolactin a potent inducer of adenomyosis in mice? AB - Uterine adenomyosis is a benign lesion but a serious disease for women, because the symptoms are characterized by abnormal bleeding, pain, cramps, and sterility. Thus elucidation of the mechanisms involved in the development of the disease would contribute to improved management and treatment and prophylaxis of this lesion. A mouse model, in which ectopic pituitary isografting is associated with an increase in the plasma level of prolactin, is useful for a rapid and frequent induction of uterine adenomyosis and can be used to study the origin of this lesion. PMID- 1853905 TI - Ultrasonographic visualization of endometrial vascularity with ectopic pregnancy. PMID- 1853906 TI - High blood pressure in pregnancy. PMID- 1853907 TI - Maternal hemodynamics in pregnancy. PMID- 1853908 TI - Epidemiology of preeclampsia and eclampsia. PMID- 1853909 TI - Are choroid plexus cysts an indication for second-trimester amniocentesis? PMID- 1853910 TI - Cigarette smoking during pregnancy in relation to placenta previa. AB - To evaluate the relationship between cigarette smoking and the occurrence of placenta previa, we used interview and medical record data to conduct a case control analysis of 69 placenta previa cases and 12,351 controls. The unadjusted relative risk estimate of placenta previa for women reported to have "ever smoked" during pregnancy relative to nonsmoking mothers was 1.9 (95% confidence interval, 1.2 to 3.0). The risk rose after adjusting for potential confounders (odds ratio, 2.6; 95% confidence interval, 1.3 to 5.5). In contrast to a previous report, the duration of smoking was not an independent risk factor for placenta previa. These results suggest that cigarette smoking during pregnancy is a determinant of placenta previa. Carbon monoxide hypoxemia, which is one possible mechanism for this association, may result in compensatory placental hypertrophy. Placentas with increased surface areas are more likely to cover the cervical os, causing placenta previa. PMID- 1853911 TI - Medication in early pregnancy: prevalence of use and relationship to maternal characteristics. AB - Medication use was assessed in a population of 4186 women who were delivered of infants at Yale-New Haven Hospital, New Haven, Connecticut, between 1980 and 1982. The frequency of over-the-counter and prescription drug use, and the association of such use with maternal characteristics was studied. Of all women, 66% used at least one drug. The mean number of drugs used by all subjects was 1.3 and, among drug users, 2.9. Of all drugs used, 68% were over-the-counter and 32% were prescription preparations. Internal analgesics, autonomic drugs, antiinfective agents, and antacids were most frequently used. Women who used prescription drugs were also more likely to use over-the-counter medications. Maternal characteristics that were associated with an increase in both over-the counter and prescription drug use were being white, smoking more than 20 cigarettes a day, using alcohol, using caffeine, and smoking marijuana. These findings suggest that women who engage in "risk-taking behavior" during pregnancy are also more likely to use medications while pregnant. PMID- 1853912 TI - Extensive pulmonary embolism presenting as severe adult respiratory distress syndrome after surgical resection of a cornual pregnancy. AB - A rare case of severe adult respiratory distress syndrome associated with a Po2 of 9 mm Hg after surgical resection of a cornual pregnancy at 10 weeks' gestation was treated successfully with positive end-expiratory pressure. The underlying cause, extensive pulmonary embolism, was subsequently revealed. The patient survived without residual brain damage. The possible causes of adult respiratory distress syndrome in pregnancy are discussed. PMID- 1853913 TI - Ten years after cryosurgical treatment of cervical intraepithelial neoplasia. AB - From 1974 to 1977 we treated 96 patients for grade 2 or 3 cervical intraepithelial neoplasia with cryotherapy. They were monitored for 10 to 14 years with an attendance rate of 98%. Treatment resulted in cure in 92%. Nine patients had persisting lesions, and three patients had a recurrent lesion. The last recurrence was diagnosed 6.7 years after cryotherapy. PMID- 1853914 TI - Recurrence of ectopic pregnancy: the role of salpingitis. AB - We evaluated the role of salpingitis on the recurrence of ectopic pregnancy from a historical cohort of 2501 women who had undergone laparoscopic examination for acute salpingitis. We used pregnancy (N = 2899) as the unit of analysis and a modified conditional logistic regression to estimate a pairwise odds ratio as a measure of the recurrence of ectopic pregnancy. Among the second or higher order of pregnancy, the recurrence was 21.7%. For pregnancies with a prior uterine pregnancy, the ectopic pregnancy rate increased with prior salpingitis scores constructed from a combination of prior salpingitis episodes and severity (0 score, 2.7%; 1 to 2 scores, 4.8%; and greater than or equal to 3 scores, 12.1%). For those with a prior ectopic pregnancy, the rate did not increase with prior salpingitis scores (score 0, 20.0%; score 1 or 2, 19.2%; and score greater than or equal to 3, 26.9%). The adjusted pairwise odds ratio was 2.2 and was practically unchanged (2.1) after additional adjustment with prior salpingitis scores. These findings confirm salpingitis as a risk factor for first ectopic pregnancy, but once a woman had an ectopic pregnancy, previous salpingitis might not add any incremental risk. PMID- 1853915 TI - The prevalence of autoantibodies during third-trimester pregnancy complicated by hypertension or idiopathic fetal growth retardation. AB - Lupus anticoagulant, anticardiolipin, antinuclear, anti-deoxyribonucleic acid, antithyroglobulin, and antithyroid microsomal antibodies were assayed during third-trimester pregnancy (100 normal, 100 with complications). In spite of a normal activated partial thromboplastin time in all instances, lupus anticoagulant was further investigated by three additional procedures: tissue thromboplastin inhibition time, platelet neutralization procedure, and cephalin neutralization test. The prevalence of autoantibodies in pregnancies with hypertension reaches 16% (four with lupus anticoagulant, two with anticardiolipin, and two with antithyroid microsomal antibodies), which is significantly greater than that for idiopathic fetal growth retardation (2%) (one with lupus anticoagulant antibodies) and normal pregnancies (3%) (two with antithyroglobulin and one with autithyroid microsomal antibodies) (p less than 0.01). Autoantibodies were equally distributed between patients with gestational hypertension and those with preeclampsia. When compared with the 42 patients with hypertension and no autoantibodies, the eight patients with autoantibody had a more frequent history of fetal growth retardation (p less than 0.05), but there was no difference in the severity of hypertension, the frequency of obstetric complications, or the outcome of pregnancy. They did not require any specific treatment. PMID- 1853916 TI - Automated analysis of near-term antepartum fetal heart rate in relation to fetal behavioral states: the Sonicaid System 8000. AB - Fetal heart rate and fetal movements were recorded in 16 uncomplicated near-term pregnancies. The recordings were used to evaluate a system for automated fetal heart rate analysis (Sonicaid System 8000). Fetal rest-activity patterns were considered in the analysis. The mean duration of C2F periods "active sleep," 33 minutes) was significantly greater than that of C1F periods ("quiet sleep," 19 minutes) (p less than 0.001). The incidence of accelerations and decelerations and the overall fetal heart rate variations were greater during C2F than during C1F (p less than 0.001). In 11 of 16 C1F periods, the system classified the fetal heart rate variation as "questionable" or "abnormal." Episodes of high variation were identified in only 3 of 16 C1F periods, but they were found in all 18 C2F periods. Episodes of low variation were identified in 14 of the 16 C1F periods but were not found in any C2F periods. During C2F periods, the system's criteria of normality were met in all cases but one; they were not met during any of the C1F periods. Thus the diagnosis of fetal distress should not be based merely on the absence of accelerations, low fetal heart rate variation, or absence of episodes of high variation in recordings with a duration of less than 45 minutes. PMID- 1853917 TI - A life-threatening sexually transmitted Haemophilus influenzae in septic abortion: a case report. AB - Haemophilus influenzae infections of the genitourinary tract are rare. A case of a life-threatening Haemophilus influenzae bacteremia associated with a septic abortion is presented. Sexual transmission of bacteria after orogenital contact is proposed as a possible source of this uncommon infection. PMID- 1853918 TI - Screening in ovarian cancer. AB - Ovarian cancer will affect 20,000 American women this year and some 13,500 will die of the disease. Most patients will have stage III or IV disease at the time of diagnosis. Because ovarian cancer may be initially without symptoms, attempts have been made to develop screening tests that would lead to an early diagnosis. Two tests, serum CA 125 and pelvic ultrasonography, have been suggested by some to be accurate enough to be included in yearly screening for ovarian cancer. Although further testing of these techniques is encouraged, data to date do not justify yearly screening with CA 125 or pelvic ultrasonography in all women. PMID- 1853919 TI - The effect of trisomy 18 on transverse cerebellar diameter. AB - The transverse cerebellar diameter was measured in 19 fetuses with trisomy 18. Eleven of the cerebellar measurements (57.9%) were greater than 2 SD below the mean for the patient's gestational age. If fetal biometry rather than last menstrual period were used to determine gestational age, four of the 19 (21.0%) cerebellar measurements were greater than 2 SD below the mean. Both intrauterine growth retardation and intrinsic central nervous system abnormalities associated with trisomy 18 appeared to affect cerebellar size. PMID- 1853920 TI - Porencephalic cyst: a complication of fetal intravascular transfusion. AB - A case of unilateral porencephalic cyst as a result of intravascular intrauterine transfusion is reported. Although other factors may have contributed, fetal bradycardia and relative hyperviscosity as a result of increased fetal hematocrit value were considered to be related to this event. Because some authors recommend direct intravascular transfusion to supraphysiologic hematocrits to prolong the interval between procedures, we would caution the use of this approach on the basis of theoretic considerations and the occurrence of this complication. PMID- 1853921 TI - Hyporegenerative anemia associated with intrauterine transfusion in rhesus hemolytic disease. AB - Serial erythropoietin and ferritin levels were monitored in a fetus and newborn requiring three intravascular transfusions (in utero) for severe Rh disease. The newborn had a hematocrit of 37% at birth; however a hyporegenerative transfusion dependent anemia developed and lasted approximately 3 months. The prolonged hyporegenerative anemia may be caused in part by erythropoietin suppression as a result of the fetal intravascular transfusions. In addition, anti-D antibody may also contribute to this anemia by a direct toxic effect on erythroid precursors and by peripheral hemolysis of reticulocytes. PMID- 1853922 TI - Daily administration of the progesterone antagonist RU 486 prevents implantation in the cycling guinea pig. AB - Since progesterone is required to prepare the endometrium for implantation of an embryo, a progesterone antagonist may inhibit nidation and thus prevent pregnancy. We addressed this possibility in the guinea pig, the small laboratory animal whose reproductive physiology most resembles that of women. Daily administration of the antiprogestin RU 486 (0, 1, 2, or 3 mg/kg, subcutaneously) for 9 days after mating inhibited implantation in a dose-dependent fashion. When this compound was given daily throughout the estrous cycle, cyclic vaginal changes, ovulation, and mating were suppressed in up to 17%, 28%, and 55% of animals, respectively. Two of seven mated female animals receiving RU 486, 1 mg/kg/day, had implantation sites. Nidation was completely blocked at higher doses. Thus daily antiprogestin administration prevented pregnancy in sexually active, normally cycling guinea pigs. A similar strategy using a daily antinidatory dose of an antiprogestin may offer a novel approach to human fertility control. PMID- 1853923 TI - Fetal heart rate response to vibroacoustic stimulation during low and high heart rate variability episodes in late pregnancy. AB - In 52 women in late pregnancy, the mean durations of transient fetal tachycardia after vibroacoustic stimulation during low fetal heart rate variability (4.8 minutes) and high fetal heart rate variability (6.3 minutes) were similar. The fetal heart rate continued with high variability in all cases, suggesting that the fetus did not return to its prestimulation state after vibroacoustic stimulation during quiescence. In 10 women, the duration of high variability after vibroacoustic stimulation during low fetal heart rate variability was significantly shorter (mean, 22 minutes) than the preceding (mean, 36 minutes) or subsequent (mean, 43 minutes) high-variability components of complete rest activity cycles. In another 10 women, the duration of high variability after vibroacoustic stimulation during high fetal heart rate variability was similar to preceding and subsequent high-variability episodes. In these 20 women, the next complete rest-activity cycle after vibroacoustic stimulation was not different in duration to the complete cycle recorded on the previous day. PMID- 1853924 TI - Elective versus emergency cesarean hysterectomy cases in a residency program setting: a review of 129 cases from 1984 to 1988. AB - A retrospective study was performed to compare elective versus emergency cesarean hysterectomy in a residency program. We noted the following statistically significant differences between emergency and elective cases: (1) Estimated blood loss (mean +/- SD) for emergency and elective cases was significantly different at 1495 +/- 772 and 875 +/- 396 ml (p = 0.001). (2) Operative time in emergency cases was significantly longer than in elective cases (105 +/- 38 vs 83 +/- 27 minutes, p = 0.003). (3) The incidence of transfusion was 68% in our emergency cases and 14.6% in the elective series (p less than 0.05). (4) Febrile morbidity in our series was 40% in emergency cases and 18.3% in elective cases (p less than 0.05). Our series was comparable to previous series reported. Our experience suggests that cesarean hysterectomy can be performed safely in a residency training program when done as an elective procedure in the well-prepared patient. PMID- 1853925 TI - Transcervical endoscopic verification of congenital anomalies in the second trimester of pregnancy. AB - Transcervical endoscopy was used to confirm prenatally diagnosed anomalies before elective termination of pregnancy. A complete anatomic survey was accomplished in 10 (70%) of 14 cases studied. Information was added to the ultrasonographic diagnosis in two cases, which changed the diagnosis in one fetus. PMID- 1853926 TI - Trophoblast from anembryonic pregnancy has both a maternal and a paternal contribution to its genome. AB - In a series of 14 anembryonic pregnancies, deoxyribonucleic acid from trophoblast was examined with locus-specific minisatellite probes. It was found in each case that trophoblast from anembryonic pregnancy has both a maternal and a paternal contribution to its genome. This means that although anembryonic pregnancy shares characteristics with complete hydatidiform mole and androgenetic development in the mouse in that there is no embryo, it does not arise by the same genetic process. Of three anembryonic pregnancies that were successfully karyotyped, two had normal female 46,XX chromosome constitutions and one had an abnormal 47,XX + 16 complement. The sex of the trophoblast in each anembryonic pregnancy was determined with a deoxyribonucleic acid probe with Y-specific bands. A male-to female ratio of 6:8 was found, which is not significantly different from normal. PMID- 1853927 TI - Lipid deposition and intimal stress and strain. A study in rats with aortic stenosis. AB - These experiments were designed to study the topography of lipid deposition in the stenotic aorta of hypercholesterolemic rats, and to correlate it with flow conditions and intimal stresses and strains studied in a scale biophysical model and in a computer model. A 69% +/- 5% stenosis was produced with a U-shaped metal clip. One month to 8 months later, the aorta was studied en face by light microscopy after fixation and lipid staining. The intima in the throat of the stenosis was almost completely free of lipid, whereas symmetric lipid deposits occurred as bands just above and especially just below the stenosis; elsewhere lipid deposits appeared to be random. The flow data obtained from the scale model showed that the intima in the throat of the stenosis was subjected to an increase of as much as 20 times in shear stress, whereas the lipid deposits just above and just below the stenosis were associated with asymmetric flow conditions: the proximal area corresponded to a region of rapidly increasing shear stress, the distal area to a region of low to normal shear stress and separated flow. A finite element computer model based on the aortic deformations indicated that the endothelium at the inlet and outlet of the stenosis is subjected to a symmetric pattern of elevated stresses and strains. These results indicate that 1) the pattern of lipid deposition can not be adequately explained by a hypothesis based solely on flow conditions, and 2) lipid deposits can develop in areas of increased fluid shear stress, decreased fluid shear stress, and increased intimal strains. PMID- 1853928 TI - Immunoreactive transforming growth factor alpha is commonly present in colorectal neoplasia. AB - Surgical specimens from 19 patients with invasive colorectal cancers and 12 specimens of normal mucosa from the same patients were examined immunohistochemically for the production of the immunoreactive (IR-) transforming growth factor (TGF)-alpha and IR-epidermal growth factor (EGF) with an anti-TGF alpha monoclonal antibody (MAb) OAL-MTG01 and anti-EGF MAb KEM-10. Immunoreactive TGF-alpha was detected in 16 (84.2%) of 19 colorectal cancers. In contrast, there was no IR-TGF-alpha in the gland cells of normal mucosa. Immunoreactive EGF was detected in 7 (36.8%) of 19 colorectal cancers and 1 (8.3%) of 12 cases of normal mucosa. The production of both IR-TGF-alpha and IR-EGF in colorectal cancer did not differ by histologic type and Dukes' stage. Immunoreactive TGF-alpha was detected at significantly higher incidence than IR-EGF in colorectal cancer. These results indicate that IR-TGF-alpha should prove valuable as a possible tumor marker in colorectal cancers, and it may be very useful in understanding the biology of colorectal cancer. PMID- 1853929 TI - Development of complex atherosclerotic lesions in pigs with inherited hyper-LDL cholesterolemia bearing mutant alleles for apolipoprotein B. AB - The development of atherosclerotic lesions was studied in pigs aged 4 to 54 months with inherited hyperlow-density lipoprotein (LDL) and hypercholesterolemia (IHLC pigs). These pigs bear the Lpb5 and Lpu1 mutant alleles for apolipoproteins B and U and demonstrate spontaneously elevated cholesterol levels, due primarily to elevated LDL. By 1 year of age, IHLC pigs exhibited focal lesions in the major coronary, iliac, and femoral arteries that were composed of macrophage-derived from cells and smooth muscle cells. Peripheral arterial lesions were more fibrous than those found in the coronaries. By 2 years of age, complicated stenotic lesions containing fibrous caps, necrotic cores, cholesterol clefts, granular calcium deposits, and neovascularization deep within the lesion were common in the major coronary vessels. Peripheral vascular lesions were more smooth muscle cell-rich and fibrotic. By 3 years of age, neovascularization was observed throughout the intimal lesion, and hemorrhage and rupture were common. The extent of complicated lesion formation correlated with both the degree and duration of hypercholesterolemia, with the most stenotic lesions observed in the coronary arteries of the oldest animals having the highest cholesterol levels. Thus IHLC pigs with mutant apolipoproteins B and U develop complicated atherosclerotic plaques that closely resemble advanced atherosclerotic lesions found in humans. PMID- 1853930 TI - Orchitis and human immunodeficiency virus type 1 infected cells in reproductive tissues from men with the acquired immune deficiency syndrome. AB - Mechanisms underlying human immunodeficiency virus type 1 (HIV-1) infection of the male reproductive tract and the sexual transmission of HIV-1 through semen are poorly understood. To address these issues, the authors performed morphologic and immunocytochemical analyses of reproductive tissues obtained at autopsy from 43 male acquired immune deficiency syndrome (AIDS) patients. Monoclonal antibodies recognizing different subpopulations of white blood cells were used to detect leukocyte infiltration and map the location of potential lymphocytic/monocytic HIV-1 host cells and immunocytochemistry and in situ hybridization techniques were used to detect HIV-1-infected cells in the testis, excurrent ducts, and prostate. Distinct pathologic changes were observed in a majority of testes of AIDS patients that included azoospermia, hyalinization of the boundary wall of seminiferous tubules, and lymphocytic infiltration of the interstitium. The reproductive excurrent ducts and prostate appeared morphologically normal except for the presence of focal accumulations of white blood cells in the connective tissue stroma. In the testis many white blood cells were shown to be CD4+, indicating the presence of abundant host cells (T helper/inducer lymphocytes and macrophages) for HIV-1. Furthermore macrophages and cells of lymphocytic morphology were observed migrating across the boundary walls of hyalinized seminiferous in tubules to enter the lumen. In 9 of the 23 cases tested for HIV-1 protein expression by immunocytochemistry. HIV-1 + cells of lymphocytic/monocytic morphology were found in the seminiferous tubules and interstitium of the testis, epididymal epithelium, and connective tissue of the epididymis and prostate. One patient with epididymal blockage had accumulations of HIV-1-antigen-positive cells of macrophages morphology in the distended lumen of the efferent ducts. There was no evidence of active HIV-1 infection in germ cells or Sertoli cells of the seminiferous tubules or other epithelial cells lining the excurrent ducts or prostatic glands. PMID- 1853931 TI - Heparin alters epidermal growth factor metabolism in cultured rat glomerular epithelial cells. AB - Extracellular matrix plays an important role in regulating cell growth. The authors have previously shown that heparin and heparan sulfate inhibit glomerular visceral epithelial cell (GEC) growth and that epidermal growth factor (EGF) can partially reverse the effect of heparin. The authors studied EGF processing by GEC in an attempt to clarify the mechanism by which heparin inhibits GEC growth. Control and heparin-treated GEC rapidly internalized 125I-EGF (within 15 minutes). In heparin-treated cells, 125I-EGF reappeared on the cell surface during the course of a 1-hour incubation and the percent internalized dropped significantly to 59.0% +/- 8.6%, suggesting recycling of 125I-EGF-occupied receptors. After incubation with 125I-EGF, heparin-treated cells also released significantly more cpm of 125I into EGF-free medium (2526 +/- 68 cpm-H; 903 +/- 32-C). Analysis of the released 125I by gel filtration chromatography showed more totally degraded 125I-EGF in media from heparin-treated cells (30.8% +/- 1.6% in heparin-treated versus 17.8% +/- 3.2 in control; P less than 0.05). Analysis of EGF-induced dimerization of receptors showed no effect of heparin on this ratio. These studies suggest that heparin decreases GEC response to EGF by accelerating its uptake and degradation. Matrix alterations in disease states may thus play a role in altering cell responsiveness to growth factors. PMID- 1853932 TI - Salmonella-induced M-cell formation in germ-free mouse Peyer's patch tissue. AB - M cells present in Peyer's patch tissue transport enteric antigens for presentation to underlying lymphoid tissue to initiate immune responses against intestinal infection. Present work investigates how interactions taking place between bacteria, epithelial cells, and immunocytes could contribute to initial detection and later elimination of enteric antigens. Oral infection of germ-free mice with Salmonella typhimurium aroA- caused a twofold to threefold increase in M cell numbers, crypt depth, and enterocyte migration rate after 7 days. These changes were accompanied by a twofold increase in follicle-associated epithelial tissue (FAE)-associated CD4+ and a threefold decrease in FAE-associated CD8+ counts. Salmonella also increased M-cell numbers shortly after infection. Other effects on crypt size and spleen weight took longer to develop. Salmonella probably creates M cells by changing the local subepithelial immune environment in the lymphoid follicle. PMID- 1853933 TI - Inducible release of an endothelial cell-specific protein. AB - The authors investigated the release of an endothelial cell-specific protein (E92) by cultured porcine aortic endothelial cell cultures. Under normal culture conditions, endothelial cells released little or no E92 into the culture supernatant. Treatment with thrombin (0.01 to 10 units/ml), endotoxin (0.01 to 10 micrograms/ml), or interleukin-1 (0.01 to 3.0 units/ml), however, caused significant, dose-dependent increases in E92 detectable in the culture supernatants. Time-course experiments showed that maximum release of E92 into cellular supernatants occurred 24 hours after stimulation with all mediators. Parallel experiments used 51Cr-loaded endothelial cells as a measure of lethal cellular injury. None of the mediators caused significant injury at the doses observed to induce release of E92. These results suggest that the release of E92 into the supernatants of cultured endothelial cells is an inducible event. The data also support the hypothesis that detection of E92 antigen in sera from patients with rheumatic disease represents a marker of in vivo vascular endothelial cell activity. PMID- 1853934 TI - Cardiac myofibroblasts express alpha smooth muscle actin during right ventricular pressure overload in the rabbit. AB - A number of changes occur in contractile proteins and mechanical performance of the heart within 2 weeks of right ventricular pressure overload in 8- to 12-week old rabbits. These changes are accompanied by increases in collagen concentration and the ratio of type I to type III collagen. The purpose of the present study was to evaluate the evolution of these connective tissue changes morphologically and to characterize the interstitial cells that might be responsible. The myocardium is infiltrated by mononuclear inflammatory cells 2 days after banding, accompanied by focal myocyte necrosis. By 7 days, the inflammatory infiltrates subside and the damaged myocytes seen at 2 days are replaced by new collagen and a population of spindle-shaped cells, with ultrastructural features of myofibroblasts. A significant proportion of these cells contain alpha smooth muscle actin by immunohistochemical analysis. At 14 days, there is a large increase in stainable collagen with complex remodeling and reduplication of the collagen fiber network of the interstitium. Alpha smooth muscle actin-containing myofibroblasts persist, but their immunoreactivity appears reduced compared with day 7. The authors hypothesize that the interstitial fibroblasts that acquire smooth-muscle-like features in this model play a critical role in the heart's response to severe and sudden mechanical stress and are at least partly responsible for the changes in connective tissue that occur as a result of pressure overload in this model. PMID- 1853935 TI - Peroxisome induction potential and lipid-regulating activity in rats. Quantitative microscopy and chemical structure-activity relationships. AB - Structurally diverse lipid-regulating agents induce hepatomegaly, hepatic peroxisome proliferation, and hepatocarcinoma in rats by mechanisms not fully understood. Nevertheless the initial hepatic response is a prompt, florid proliferation of peroxisomes. In investigations reported here, changes in the rat hepatic peroxisome compartment were measured by quantitative microscopy to determine chemical structure requirements that relate to peroxisome proliferation and lipid regulation. Aryloxyalkanoic acids plus amide analogs, and thio, benzimidazole, phenylpiperazine, and oxazole derivatives induced peroxisome proliferation and generally decreased plasma triglyceride and total cholesterol levels. These compounds contain an acidic function or are readily metabolized to a chemical with an acidic function. Substitution of the acidic function with an adamantyloxy eliminated peroxisome proliferation and induced contrasting effects on lipid profile, increasing triglycerides and decreasing total cholesterol. A previously unreported, direct correlation emerged between peroxisome proliferation and plasma high-density lipoprotein-cholesterol levels. These effects could not be elicited separately, negating identification of functional groups that could be associated with either activity. Chemical structure and resulting peroxisome proliferation with changes in plasma lipoproteins are therefore closely interrelated in rats. PMID- 1853936 TI - Intratumoral T lymphocytes from small cleaved follicular center cell lymphomas show unrestricted T-cell receptor alpha-chain variable region gene usage. AB - The relationship between the reactive T cells and neoplastic B cells of follicular center cell lymphomas is unclear. It is not known whether the T cells are recruited nonspecifically by the neoplastic B cells or are responding through the T-cell antigen receptor (TCR), to tumor-related antigen(s). This question was addressed by polymerase chain reaction analysis of TCR alpha chain variable (V) region gene expression in intratumoral T lymphocytes from three cases of small cleaved follicular center cell lymphoma. In all three cases studied, the tumor associated T cells showed unrestricted expression of all 18 alpha-chain V region genes. These findings imply that the T cells admixed with the neoplastic B cells of small cleaved follicular center cell lymphomas are not recruited based on TCR recognition of a single or limited number of tumor-related antigens. PMID- 1853937 TI - Macrophage-tropic variants of SIV are associated with specific AIDS-related lesions but are not essential for the development of AIDS. AB - The importance of macrophage infection for the development of acquired immune deficiency syndrome (AIDS) was investigated. Molecularly cloned simian immunodeficiency virus (SIV)mac239 replicates very poorly in cultured macrophages yet it causes AIDS in rhesus monkeys. Three of five rhesus monkeys that died with AIDS following SIVmac239 infection showed no disease manifestations directly associated with macrophage infection, such as encephalitis and granulomatous interstitial pneumonia. Simian immunodeficiency virus recovered from the peripheral blood of these three animals at or near the time of death replicated very poorly if at all in cultured macrophages, and tissues taken at autopsy showed little or no infection of macrophages by immunohistochemical staining. However two of the five rhesus monkeys that died with AIDS following SIVmac239 infection displayed a characteristic SIV-related meningoencephalitis and/or granulomatous pneumonia, lesions associated with macrophage infection. Simian immunodeficiency virus recovered from the peripheral blood of these two animals near the time of death replicated extremely well in cultured macrophages, indicating the emergency of macrophage-tropic variants in vivo. Furthermore tissues taken at autopsy from these two showed many infected macrophages by immunohistochemical staining. These results indicate that AIDS and death can occur without obvious involvement of macrophage infection. However the presence of macrophage-tropic viral strains appears to influence the disease course and disease manifestations. PMID- 1853938 TI - On the squamosal suture of KNM-WT 17000. AB - The extensive overlap of the temporal squama on the parietal in KNM-WT 17000 is restricted to a narrow segment of the arc of the squamosal suture. It appears as a long, narrow, posterosuperior extension onto the calvarial wall. The long axis of this extended strip is aligned with what appears to be the most hypertrophied section of the temporalis muscle fan. The substantial differences between the squamosal suture and associated masticatory elements of KNM-WT 17000 and those of Australopithecus boisei provide an opportunity to evaluate the various forces molding the anatomy of the squamosal suture of A. boisei. It is suggested that the extreme flare of the zygomatic arches in the latter accounts for these differences. PMID- 1853939 TI - Tooth and bone development in a Danish medieval mandible with unilateral absence of the mandibular canal. AB - A Danish anthropological collection of medieval human skeletons excavated in 1986 involves a mandible (No. 212) from an adult female born without the lower alveolar nerve and mandibular canal. It is believed that the defect has resulted in lack of tooth development on the affected side and that the mylohyoid nerve has partially compensated for this defect by development of teeth in localized areas. The defective mandibular dentition has caused a compensatory development of the alveolar process in the maxilla. The missing occlusal support has altered muscular traction on the mandible. This has caused an alteration in mandibular shape. Whether the asymmetric development of the mandible is caused by muscular dysfunction, by failure in angular growth apposition, or by a combination of these factors is discussed. The case presents valuable data in the ongoing discussion about the interaction between nerve tissue and tooth formation and about the interaction between occlusion, jaw morphology, and muscular traction. The study shows how archeological material in an interdisciplinary cooperation between archeological, embryological and orthodontic research can contribute to the clarification of current biological problems. PMID- 1853940 TI - Root dentine transparency: age determination of human teeth using computerized densitometric analysis. AB - Root dentine transparency (RDT) was used to estimate the ages of human subjects from 152 intact teeth. Teeth were from 134 subjects, both historical and recent, of known age and sex. The aims of this work are 1) to compare two methods of using RDT to estimate age; 2) to test the applicability of the regression formulae for estimating age obtained from a recent sample on an historical sample; and 3) to estimate the suitability of RDT to determine age at death of 100-year-old skeletons. RDT was measured by two techniques: 1) computerized densitometric analysis and 2) vernier caliper. Age estimations based on computerized densitometric analysis were no more accurate than were those determined by caliper measurement; both give a predictive success of +/- 5 years in about 45-48% of cases for premolars. The television-based digitization system has some disadvantages: It is expensive, not portable, and requires some training to use. However, it furnishes a more standardized method, a rapid graphic illustration of the results, and an immediate storage of statistical information for future use. PMID- 1853941 TI - Enamel structure and microwear: an experimental study of the response of enamel to shearing force. AB - The anisotropic fracturing and differential wear properties of enamel microstructure represent factors that can obscure the predictive relationship between dental microwear and diet. To assess the impact of enamel structure on microwear, this in vitro experimental study examines the relative contributions to wear of three factors: 1) species differences in microstructure, 2) direction of shearing force relative to enamel prisms and crystallites, and 3) size of abrasive particles. Teeth of Lemur, Ovis, Homo, and Crocodylus, representing, respectively, the structural categories of prismatic patterns 1, 2, and 3 and nonprismatic enamel, were abraded by shearing forces (forces having a component directed parallel to abraded surfaces) and examined by scanning electron microscopy. Striation width increased with particle size for nonprismatic, but not for prismatic, specimens. Direction of shear relative to prism and crystallite orientation had a significant influence on striation width in only some prismatic enamels. The different responses of prismatic and nonprismatic enamels to abrasion reflect the influence of structure, but at the level of organization of crystallites rather than prisms per se. Such interactions explain in part the inability of striation width to discriminate among animals with different dietary habits. Heteroscedasticity and deviations from normality also may confound parametric analyses of microwear variables. Variation in crystallite orientation in prismatic enamels may contribute to optimal dental function through the property of differential wear in functionally distinct regions of teeth. PMID- 1853942 TI - Blood genetic systems in four Amazonian tribes. AB - Data on 31 genetic systems were obtained for 421 individuals belonging to the Arara, Arawete, Mundurucu, and Jamamadi tribes of northern Brazil. The Jamamadi depart farthest, and the Mundurucu least, from South American Indian averages. These data are analyzed together with those of 24 other Amazonian groups. Genetic distances and corresponding dendrograms indicate a cluster of 14 related tribes living north of the Amazon river. These genetic results show only a modest correlation with linguistic and geographic relationships among these groups. PMID- 1853943 TI - Trivers-Willard effect in contemporary North American society. AB - The Trivers-Willard hypothesis joins the ideas of R.A. Fisher and A.J. Bateman to model parental investment strategies. Trivers and Willard argue that any overall investment bias favoring either daughters or sons would be maladaptive. Nevertheless, they suggest that, in effectively polygynous species, more complex, conditional sex biases could be adaptive. In particular, they predict that parents in good condition will bias their investment toward sons and that parents in poor condition will bias their investment toward daughters. Among a sample of approximately 900 U.S. mothers we examined several measures of maternal investment including birth weight, interbirth interval and lactational commitment. Maternal condition was assessed by income and by the presence or absence of a coresident adult male. Some measures of investment (five of 14 statistical tests) showed marked and significant sex-by-condition interactions of the type and in the direction predicted by Trivers and Willard; none showed significant effects in the opposite direction. No conscious mediation is required to produce the observed investment patterns. PMID- 1853944 TI - Possible congenital hemolytic anemia in prehistoric coastal inhabitants of Israel. AB - The spread of thalassemia among prehistoric populations of the Mediterranean Basin has been linked to the increased risk to early agriculturalists posed by the Plasmodium falciparum parasite. The diagnosis of the disease in human skeletal remains, however, has usually been based on a single pathological criterion, porotic hyperostosis. This paper reports on what we believe to be the earliest case of thalassemia yet identified in the prehistoric record. Our diagnosis of the disease in an individual from the submerged Prepottery Neolithic B village of Atlit-Yam off the Israeli coast is based on a pathological humerus demonstrating a pattern of deformation characteristic of clinical thalassemia. The implications of these findings for our understanding of human societies undergoing the transition from foraging to agriculture in the Near East are discussed. PMID- 1853945 TI - EMG of serratus anterior and trapezius in the chimpanzee: scapular rotators revisited. AB - The importance of arm-raising has been a major consideration in the functional interpretation of differences in shoulder morphology among species of nonhuman primates. Among the characters that have been associated with enhancement of the arm-raising mechanism in hominoid primates are the relative enlargement of cranial trapezius and caudal serratus anterior, as the main scapular rotators, as well as changes in scapular morphology associated with their improved leverage for scapular rotation. Yet in an EMG study of cranial trapezius and caudal serratus anterior function in the great apes, Tuttle and Basmajian (Yrbk. Phys. Anthropol. 20:491-497, 1977) found these muscles to be essentially inactive during arm-raising. Although Tuttle and Basmajian suggest that the cranial orientation of the glenoid fossa in apes has reduced the demand for scapular rotation during arm-raising, subsequent EMG studies on other primate species suggest that these muscles do play a significant role in arm motion during active locomotion. This paper presents a reexamination of muscle recruitment patterns for trapezius and caudal serratus anterior in the chimpanzee. All but the lowest parts of caudal serratus anterior were found to be highly active during arm raising motions, justifying earlier morphological interpretations of differences in caudal serratus anterior development. The lowest digitations of this muscle, while inactive during arm-raising, displayed significant activity during suspensory postures and locomotion, presumably to control the tendency of the scapula to shift cranially relative to the rib cage. Cranial trapezius did not appear to be involved in arm-raising; instead, its recruitment was closely tied to head position. PMID- 1853946 TI - Coat color and biochemical variation in Amazonian wild populations of Alouatta belzebul. AB - A comparative study of 13 blood genetic systems and pelage color variation was performed in four wild populations of Alouatta belzebul. The animals from the west bank of the Tocantins River showed less color variation than those from the east bank, as well as less than those from Tocantins Island. The blood genetic markers, however, revealed an opposite pattern of variation. A previously undescribed morphological variant (completely red) was observed in one specimen of the east bank, where pelage color of the local population varied from completely black to completely red. Levels of heterozygosity and inter- and intralocus variances for the blood systems are compared with those observed in five other species of New World primates. PMID- 1853947 TI - Ontogenetic perspective on mechanical and nonmechanical models of primate circumorbital morphology. AB - Dimensions of the supraorbital torus, postorbital bar, and postorbital septum were collected in an ontogenetic series of Macaca fascicularis and compared with expectations based on models that attribute morphological variation in these features to spatial factors, allometry, anterior dental loading, and neurofacial torsion. Each model was evaluated using correlation, partial correlation, and regression techniques (model I/least squares; model II/reduced major axis) applied to log-transformed and size-corrected data. Results indicate clearly that face or skull size is the primary determinant of variation in circumorbital structures. Strong support is found for the influence of spatial influences on anteroposterior supraorbital torus development (Moss and Young, Am. J. Phys. Anthropol. 18:281-292, 1960). Only minor support is noted for the neurofacial torsion model of Greaves (J. Zool. 207:125-136, 1985), and no support is indicated for the anterior dental loading model. The sexes do not differ significantly in any relevant comparisons of ontogenetic trajectories. PMID- 1853948 TI - Prolactin and cortisol responses to d-fenfluramine in major depression: evidence for diminished responsivity of central serotonergic function. AB - OBJECTIVE: Theoretically, d-fenfluramine should be a more selective serotonin (5 HT) challenge agent and has much greater clinical tolerance than the racemic compound that has previously been used. The authors' goal, therefore, was to look at 5-HT function in depression using the d isomer of fenfluramine as a probe. METHOD: They evaluated central 5-HT function in 23 patients with DSM-III-R diagnosed major depression and 16 healthy control subjects. The depressed group included 10 men and 13 women; four were outpatients, two attended a day hospital facility, and 17 were inpatients. Subjects were cannulated at 8:30 a.m. after an overnight fast. After baseline samples were drawn, 30 mg of d-fenfluramine was administered orally and blood samples were drawn over the following 5-hour period for prolactin and cortisol estimation. RESULTS: The plasma prolactin responses of the depressed patients were significantly lower than those of the control subjects. This blunting was not related to the severity of the depression but was significantly related to the patients' levels of state anxiety. Cortisol responses as well as prolactin responses were impaired in depression. High baseline cortisol levels were correlated with the severity of depression and the presence of weight loss. CONCLUSIONS: Overall, these findings indicate that there is diminished 5-HT responsivity in the depressed state. PMID- 1853949 TI - Correlates of psychiatric distress among wives of hemophilic men with and without HIV infection. AB - OBJECTIVE: The authors' objectives were 1) to examine symptoms of depression, anxiety, and anger-hostility among the wives of men with hemophilia, a major risk group for AIDS, and 2) to identify psychosocial characteristics of the women and/or their husbands that were associated with elevated distress in the women. METHOD: Thirty-six women married to men with hemophilia were studied; the husbands of 17 of these women were HIV-seropositive. The men were drawn from the population of adults with hemophilia residing in a 24-county region of western Pennsylvania. Measures of wives' psychiatric symptoms were obtained, as were measures in three psychosocial domains: predispositional sociodemographic characteristics, psychosocial stressors, and husbands' strategies for coping. RESULTS: The psychiatric symptoms of the women did not differ as a function of their husbands' serostatus or across subgroups defined according to stages of HIV infection or clinical severity of hemophilia. Instead, other factors--perceptions of personal risk of AIDS, husbands' use of particular coping styles with respect to HIV infection, and the experience of other life events--were the principal correlates of psychiatric distress. CONCLUSIONS: HIV infection acted primarily as an indirect source of stress for these women, mediated by other psychosocial characteristics of both the women and their HIV-seropositive husbands. Mental health interventions for caregivers of HIV-seropositive individuals should target the identified psychosocial correlates of psychiatric distress. PMID- 1853950 TI - Disturbances of hypothalamic-pituitary-adrenal axis functioning during ethanol withdrawal in six men. AB - OBJECTIVE: Excessive exposure to glucocorticoids can have neurotoxic effects. The behavioral, cognitive, and neurochemical changes observed following the cessation of heavy drinking, therefore, may be associated with disturbances of the hypothalamic-pituitary-adrenal (HPA) axis. To investigate HPA axis disturbances during the ethanol withdrawal syndrome, the authors examined diurnal changes in plasma cortisol in six alcohol-dependent men following the abrupt discontinuation of alcohol intake. METHOD: Plasma cortisol concentrations were quantified every 30 minutes for 24 hours in the early stage (1 day after cessation) and the middle to late stage (3 days after cessation) of the ethanol withdrawal syndrome as well as after the resolution of acute symptoms (8 days or more after cessation). RESULTS: Plasma cortisol concentrations were almost twice as high during acute withdrawal as they were following recovery. The duration of the cortisol diurnal cycle on the first day of withdrawal was negatively correlated with the severity of withdrawal. CONCLUSIONS: There is a marked activation of the HPA axis associated with the ethanol withdrawal syndrome. The authors hypothesize that this activation may account for some of the signs and symptoms of acute and subacute withdrawal. They discuss the potential long-term physiological effects of the episodic increases in cortisol associated with repeated episodes of ethanol withdrawal. The alterations in cortisol rhythmicity during early withdrawal may also have clinical implications. PMID- 1853951 TI - Childhood antecedents of homelessness in psychiatric patients. AB - OBJECTIVE: This study examined the relationship between childhood experience and homelessness in psychiatric patients. METHOD: Three large and diverse samples of homeless patients (N = 512) were compared with a sample of patients who had never been homeless (N = 271), with respect to childhood experience of foster care, group home placement, and running away. One of the homeless samples and the never homeless sample were drawn from patients admitted to a state mental hospital. In this state hospital population, risk ratios for lifetime prevalence of homelessness could be derived. RESULTS: In the three homeless samples, over 15% had a history of foster care, over 10% had a history of group home placement, and over 20% had a history of running away. These figures compared with 2%, 1%, and 5%, respectively, in the never homeless sample. In the state hospital, the lifetime prevalence of homelessness in patients with any one of these childhood experiences was about threefold that of other patients. A history of homelessness was reported by the great majority of state hospital patients who had had one of these childhood experiences. CONCLUSIONS: These childhood experiences were strongly associated with adult homelessness in these psychiatric patients. It might be possible to prevent homelessness in some cases by interventions aimed at patients with such childhood histories. PMID- 1853952 TI - Screening for dysfunction in the children of outpatients at a psychopharmacology clinic. AB - OBJECTIVE: The goals of this study were 1) to determine whether the use of the Pediatric Symptom Checklist in an adult-oriented psychiatric practice was feasible, 2) to determine if scores indicative of dysfunction on the Pediatric Symptom Checklist were associated with parental or background factors, 3) to determine whether children flagged by their scores on the Pediatric Symptom Checklist were receiving psychiatric services, and 4) to compare the psychosocial dysfunction in this group of children with that found in children screened as part of routine pediatric visits. METHOD: Adult outpatients in a hospital's clinical psychopharmacology unit were asked to complete the Pediatric Symptom Checklist regarding their children. These patients were the parents of 100 school aged children. Factors such as the parents' diagnoses and demographic variables were also examined. RESULTS: The Pediatric Symptom Checklist was readily accepted by parents and fit easily into the routine of general psychiatric practice. Significantly more of the children of these outpatients than of children in comparable pediatric offices had scores indicative of psychiatric dysfunction (scores above the cutoff). Children of parents who were single, of low socioeconomic status, or with a diagnosis of personality (especially borderline) or mood disorder were more likely to have scores above the cutoff. More than a third of the children who had scores above the cutoff on the Pediatric Symptom Checklist were not currently receiving psychiatric services. CONCLUSIONS: The Pediatric Symptom Checklist provided a rapid and simple method for general psychiatrists to identify psychosocial dysfunction in their patients' children. PMID- 1853953 TI - Determining disability due to mental impairment: APA's evaluation of Social Security Administration guidelines. AB - OBJECTIVE: APA evaluated the Social Security Administration's (SSA's) medical standards and guidelines for determining disability due to mental impairment to determine how well the standards and guidelines operationalize the statutory definition of disability in a manner consistent with current psychiatric practice. METHOD: Seventy-two psychiatrists were trained in one of two procedures: those in the sequential evaluation condition were trained in the process and forms used by the SSA's reviewing medical consultants, and those in the statutory definition condition were trained in the statutory definition of disability and application of clinical judgment according to this standard. Decisions regarding claimant's ability or inability to work were recorded on an instrument designed for the study. Each condition consisted of 12 panels of three members. They reviewed 732 actual claims for disability benefits. The panelists reviewed claims independently, then rendered panel judgments. Each claim was reviewed by one panel in each condition. RESULTS: The proportion of agreement between conditions for panel decisions (0.77) was higher than chance agreement (kappa = 0.46). The high level of agreement on claims judged to have good medical evidence and on which confident decisions were made (proportion of agreement = 0.96, kappa = 0.78) suggests that disagreements largely reflected ambiguities in application of the standards and guidelines to more complex cases or those with inadequate information. CONCLUSIONS: The SSA's revised medical standards and guidelines reflect clinical decisions about ability to work based on the statute and, with procedural modifications, should be retained. The SSA should be involved in further systematic studies to develop a field of scientific inquiry into disability and psychiatric disorders. PMID- 1853954 TI - Cost offset from a psychiatric consultation-liaison intervention with elderly hip fracture patients. AB - OBJECTIVE: The authors hypothesized that psychiatric liaison screening of elderly patients with hip fractures would shorten the average length of hospital stay and increase the proportion of patients who returned home after discharge. METHOD: The study was performed at Mount Sinai Medical Center in New York and Northwestern Memorial Hospital in Chicago. The subjects were 452 patients 65 years or older who were consecutively admitted for surgical repair of fractured hips. During a baseline year the patients received traditional referral for psychiatric consultation. During the experimental year all the patients at Mount Sinai and the patients on one Northwestern Unit were screened for psychiatric consultation. RESULTS: The patients who received psychiatric liaison screening had a higher consultation rate than those who received traditional consultation. The rates of DSM-III disorders in the experimental year were 56% at Mount Sinai and 60% at Northwestern. The mean length of stay was reduced from 20.7 to 18.5 days at Mount Sinai and from 15.5 to 13.8 days at Northwestern, resulting in reductions in hospital costs ($647/day) of $166,926 and $97,361, respectively. Fees generated from Medicare service delivery could have paid for the $20,000 psychiatric intervention cost at each site. There was no difference, however, between the two years in the discharge placement of patients. CONCLUSIONS: Admission psychiatric liaison screening of elderly patients with hip fractures results in early detection of psychiatric morbidity, better psychiatric care, earlier discharge, and substantial cost savings to the hospital. PMID- 1853955 TI - Detection of dissociative disorders in psychiatric patients by a screening instrument and a structured diagnostic interview. AB - OBJECTIVE AND METHOD: Diagnosis and treatment of the dissociative disorders may be delayed for many years because of difficulties in detecting patients at high risk for dissociative disorders. This study investigates the utility of the Dissociative Experiences Scale (DES), a self-report instrument for dissociative experiences, in detecting patients at high risk for dissociative disorders. The clinician-administered Structured Clinical Interview for DSM-III-R Dissociative Disorders (SCID-D) was used as the diagnostic standard, and 36 outpatients with mixed diagnoses and nine normal subjects were evaluated for the presence and absence of a dissociative disorder. DES scores were then compared. RESULTS: Results indicate that a DES cutoff score of 15-20 yields good to excellent sensitivity and specificity as a screening instrument. However, for higher cutoff points the sensitivity can be much lower. CONCLUSIONS: Thus, although the DES can be used to identify some high-risk patients, they should be further evaluated with such diagnostic instruments as the SCID-D or by in-depth clinical follow-up. PMID- 1853956 TI - Comparison of the effects of hydrochlorothiazide and furosemide on lithium disposition. AB - OBJECTIVE: This study examined the interaction between lithium and diuretics, comparing both the pharmacokinetic and the pharmacodynamic variable of hydrochlorothiazide, furosemide, and placebo. METHOD: The study, which took place in an outpatient research clinic of a university hospital, used a double-blind, placebo-controlled crossover design. The subjects were normal, healthy male volunteers who responded to recruitment announcements. Thirteen subjects entered and completed the study. All subjects took lithium, 300 mg b.i.d., for 6 weeks. Hydrochlorothiazide, 25 mg b.i.d.; furosemide, 20 mg b.i.d.; and placebo were given during weeks 2, 4, and 6 in a random order of assignment. Serum lithium levels and indices of diuretic activity were measured during each week. RESULTS: The subjects' serum lithium levels after 5 days of taking hydrochlorothiazide were significantly higher than after 5 days of taking furosemide and placebo. At the doses studied, hydrochlorothiazide was also more potent than furosemide in increasing plasma renin activity, increasing sodium excretion, and decreasing lithium excretion. CONCLUSIONS: The observed differences between diuretics in effects on serum lithium may have been due to differences in the potency of the diuretics at the doses studied as well as in the site of action of the diuretic effect. The results must be interpreted cautiously, however, because the effects were small and of questionable clinical significance, and the study used healthy volunteers and low doses of lithium instead of psychiatric patients and the usual therapeutic levels of lithium. PMID- 1853957 TI - Fluoxetine in the treatment of borderline and schizotypal personality disorders. AB - Twenty-two patients meeting the criteria for borderline or schizotypal personality disorder or both participated in a prospective, nonblind 12-week trial of fluoxetine. There were significant reductions in self-injury and in scores on the Hopkins Symptom Checklist regardless of diagnosis. The results suggest that controlled trials of fluoxetine and investigations of the serotonergic system in these disorders would be useful. PMID- 1853958 TI - Manic syndrome in AIDS. AB - A manic syndrome in eight patients with AIDS is described. On the basis of clinical, neuropsychological, laboratory, magnetic resonance imaging, and epidemiological evidence, the authors suggest that the manic syndrome was secondary to HIV infection. The patients also developed concomitant cognitive impairment. PMID- 1853959 TI - Decrease in resting metabolic rate during abstinence from bulimic behavior. AB - Among eight normal-weight bulimic women studied during 1 week of binge eating and vomiting and 7 weeks of abstinence without weight loss, resting metabolic rate and T3 and T4 levels fell significantly during abstinence. These data suggest that a physiological consequence of binge eating and vomiting is an increase in metabolic rate, in part due to increased thyroid hormone activity. PMID- 1853960 TI - The course of psychological symptoms after resolution of lawsuits. PMID- 1853961 TI - Prevalence of substance abuse in psychiatric patients. PMID- 1853962 TI - Divalproex in posttraumatic stress disorder. PMID- 1853963 TI - The obsessive quality and clomipramine treatment in PTSD. PMID- 1853964 TI - DSM-III-R criteria for cocaine disorders. PMID- 1853965 TI - Bruxism and sexual abuse. PMID- 1853966 TI - Fluoxetine in autism. PMID- 1853967 TI - Treatment of cancer phobia with fluoxetine. PMID- 1853968 TI - Preoccupation with suicide in patients treated with fluoxetine. PMID- 1853969 TI - Prediction of suicide. PMID- 1853970 TI - Need for reporting of gender differences. PMID- 1853971 TI - Innovations in use of pharmacological treatments. PMID- 1853972 TI - Comments on the natural history of alcohol abuse. PMID- 1853973 TI - Social phobia and agoraphobia in alcoholism. PMID- 1853974 TI - Nonpurging bulimia nervosa and binge eating disorder. PMID- 1853975 TI - Request for more information about study of rapid cycling in affective disorders. PMID- 1853976 TI - Factors influencing response to placebo. PMID- 1853977 TI - Severe forms of tardive dyskinesia. PMID- 1853978 TI - Trauma in childhood. PMID- 1853979 TI - Behavioral disorders in animals. PMID- 1853980 TI - Cortical glucose metabolism and clinical depression. PMID- 1853981 TI - Cyclothymic mood swings in major and minor psychiatric disorders. PMID- 1853982 TI - Hypnotizability and dissociation. PMID- 1853983 TI - Dissociative disorders and complex partial seizures. PMID- 1853984 TI - Computerized literature searches. PMID- 1853985 TI - Maladaptive denial of pregnancy. PMID- 1853986 TI - Third-party management of utilization of health services. PMID- 1853987 TI - Magnetic resonance spectroscopy in psychiatry: potential, pitfalls, and promise. AB - Magnetic resonance spectroscopy (MRS) is a novel noninvasive approach to measuring important metabolites in living tissue. Its application to psychiatry is just beginning. In vivo MRS with 31P provides important information on brain phospholipid metabolism and energy production. In vivo 13C and 1H MRS can reveal information about carbohydrate, protein, and amino acid metabolism. In vivo 7Li and 19F MRS can be used to study the pharmacology of lithium and fluorinated psychopharmacological agents. MRS with 23Na can yield information about electrolyte balance. The limitations of in vivo MRS include poor sensitivity, poor resolution, and the fact that only highly mobile atomic nuclei can be detected. Future clinical application of MRS will benefit from improvements in the technology of localization, use of spectroscopy contrast agents, stronger magnets, and the merging of MRS and imaging technology. PMID- 1853988 TI - Kleptomania: making sense of the nonsensical. AB - OBJECTIVE: Kleptomania, or the irresistible impulse to steal unneeded objects, is a poorly understood disorder. The objectives of this paper are to critically review and integrate existing data and to make suggestions for further research. DATA COLLECTION: Information was gathered by reviewing the English-language literature on kleptomania. Cases were chosen for review that approximated the diagnosis as defined in DSM-III-R. These cases were analyzed in terms of their relationship to previous theories about the disorder, and larger relevant studies were examined. Using the data organized into a table, the author explores areas of convergence and disagreement and discusses the methodological difficulties of the different studies. FINDINGS: Kleptomania is more common than previously thought. The "typical" individual with kleptomania is a 35-year-old woman who began to steal when she was 20 years old. Her thefts bring both relief and guilt. She probably has not sought treatment on her own but suffers from a necessary, pervasive, repetitive, and self-destructive act. She may have a history of sexual dysfunction or sexual preoccupation and may be unhappily married to an emotionally unsupportive husband. She has been labile and dysphoric for many years and may have a personality disorder. She has probably had a tumultuous, stressful childhood and may dissociate. CONCLUSIONS: The author proposes a biopsychosocial model of the etiology of kleptomania based on data from the literature. This model emphasizes possible childhood abuse as a precipitating factor in later development of kleptomania. More complete research is needed in the study of kleptomania. PMID- 1853989 TI - Patient predictors of response to psychotherapy and pharmacotherapy: findings in the NIMH Treatment of Depression Collaborative Research Program. AB - OBJECTIVE: The authors investigated patient characteristics predictive of treatment response in the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program. METHOD: Two hundred thirty-nine outpatients with major depressive disorder according to the Research Diagnostic Criteria entered a 16-week multicenter clinical trial and were randomly assigned to interpersonal psychotherapy, cognitive-behavior therapy, imipramine with clinical management, or placebo with clinical management. Pretreatment sociodemographic features, diagnosis, course of illness, function, personality, and symptoms were studied to identify patient predictors of depression severity (measured with the Hamilton Rating Scale for Depression) and complete response (measured with the Hamilton scale and the Beck Depression Inventory). RESULTS: One hundred sixty-two patients completed the entire 16-week trial. Six patient characteristics, in addition to depression severity previously reported, predicted outcome across all treatments: social dysfunction, cognitive dysfunction, expectation of improvement, endogenous depression, double depression, and duration of current episode. Significant patient predictors of differential treatment outcome were identified. 1) Low social dysfunction predicted superior response to interpersonal psychotherapy. 2) Low cognitive dysfunction predicted superior response to cognitive-behavior therapy and to imipramine. 3) High work dysfunction predicted superior response to imipramine. 4) High depression severity and impairment of function predicted superior response to imipramine and to interpersonal psychotherapy. CONCLUSIONS: The results demonstrate the relevance of patient characteristics, including social, cognitive, and work function, for prediction of the outcome of major depressive disorder. They provide indirect evidence of treatment specificity by identifying characteristics responsive to different modalities, which may be of value in the selection of patients for alternative treatments. PMID- 1853990 TI - Controlled trial of Giardia lamblia: control strategies in day care centers. AB - BACKGROUND: Strategies for control of Giardia lamblia in day care differ in numbers of children treated and in costs to parents and day care operators. The effectiveness of these strategies has not been systematically evaluated. METHODS: We conducted a prospective randomized controlled trial comparing three strategies for control of Giardia in infant-toddler day care centers: Group 1, exclusion and treatment of symptomatic and asymptomatic infected children; Group 2, exclusion and treatment of symptomatic infection only; Group 3, exclusion and treatment of symptomatic infection, treatment of asymptomatic infection in the center. The study included 31 day care centers with 4180 child-months of observation. Giardia prevalence was determined before intervention and 1, 2, 4, and 6 months later; new infants and toddlers were tested on admission. RESULTS: Initial Giardia prevalences were 18% to 22% in the three groups. Giardia was identified in 10.5% of 676 new infants and toddlers entering study day care centers during the 6 month follow-up. Giardia prevalences by intervention group were 8%, 12%, and 7% at 1 month, and 7%, 8%, and 8% at 6 months. CONCLUSIONS: The stricter intervention resulted in greater cost in terms of child day care and parents' work days lost, but did not result in significantly better control of Giardia infections in this day care environment. PMID- 1853991 TI - Characteristics of maternal employment during pregnancy: effects on low birthweight. AB - BACKGROUND: Although maternal employment is considered a risk factor for low birthweight (LBW), the manner in which employment might affect birthweight is poorly understood. In this analysis, selected characteristics of employment during pregnancy were examined for effects on pregnancy outcomes. METHODS: Work characteristics included the number of hours per week, physical activities, and environmental conditions. The outcomes of interest were fetal growth retardation (less than 2500 grams at term) and preterm delivery (less than 37 weeks). The study population consisted of 2711 non-Black, married mothers who participated in the 1980 National Natality Survey (NNS). The NNS data were merged with data from the 1977 revision of The Dictionary of Occupational Titles (DOT) from which measures of occupational physical activities and environmental exposures were obtained. Logistic regression was used in the analysis. RESULTS: Those who worked 40 or more hours per week were more likely than women who worked fewer hours to have a low birthweight delivery at greater than or equal to 37 weeks. No physical or environmental characterics of work were associated with low birthweight or preterm delivery. CONCLUSIONS: Non-Black married American women may face a risk of delivering low-birthweight babies at or near term only if they work 40 or more hours each week. However, the lack of risk associated with other characteristics of work may be a function of measurement error in the DOT data source or of low levels of exposure in the analysis population. PMID- 1853992 TI - Source of bias in prenatal care utilization indices: implications for evaluating the Medicaid expansion. AB - BACKGROUND: Recent expansions in eligibility for coverage of prenatal care services by the Medicaid program reflect national initiatives to improve pregnancy outcomes. This study investigates the potential impact that completeness of reporting of prenatal care and gestational age variables and strategies to impute missing data may have on evaluations of the Medicaid expansion. METHODS: This study, examining 15 years of vital record data from a single state and comparing 1 year of data from four mid-Atlantic states, selected single live births to resident mothers for analyses. The "day 15" and the "preceding case" methods were used to impute missing gestational age data. RESULTS: Considerable temporal and geographic variation was detected in completeness of reporting of variables used to construct prenatal care indices. After imputing values for cases with missing data, the proportion of cases for which adequacy of prenatal care utilization could not be determined ranged from 3% to 24% among the states investigated. For those cases where gestational age data could be imputed, the distribution of prenatal care utilization was not markedly disparate from those cases with complete reporting of gestational age. CONCLUSIONS: The results indicate that variations in reporting, decisions regarding the treatment of missing data, and the choice of the denominator can alter prenatal care utilization percentages and have implications for evaluations of the impact of the recent Medicaid expansion on prenatal care utilization. PMID- 1853993 TI - Uncompensated hospital care for pregnancy and childbirth cases. AB - BACKGROUND: The large number of medically indigent patients in the United States is a major concern to policymakers and may be due to recent increases in the number of uninsured people. The purpose of this study was to identify the factors that affect the amount of unpaid hospital charges for services provided to pregnant women. METHODS: Individual and hospital data were collected on a representative set of 235 pregnancy and childbirth patients with unpaid hospital charges from 28 hospitals in the state of Indiana. RESULTS: Most of these patients did not have insurance coverage (63.8%), yet the majority were employed in the public or private sector (72.3%). Over half (55.5%) of the total uncompensated care amount for this group was from the $1000 to 2499 debt category. The median charge for these patients was $1468, of which the typical hospital was able to collect only 25.5%. CONCLUSIONS: The findings support the belief that any national effort to expand the availability of health insurance coverage to women through increased employment will not totally eliminate the uncompensated care problem. The findings also indicate that rural hospitals face the uncompensated care problem mainly because a significant portion of rural patients are without adequate health insurance coverage. PMID- 1853994 TI - Effects of paternal occupational exposure on spontaneous abortions. AB - BACKGROUND: Paternal exposure to mutagenic agents has been suggested to affect pregnancy outcome adversely. METHODS: A nationwide data base of medically diagnosed spontaneous abortions and other pregnancies and national census data was used to evaluate the effects of men's occupational exposures on risk of spontaneous abortion in 99,186 pregnancies in Finland. Census data from the years 1975 and 1980 provided information about the occupation, industry, and socioeconomic status. A job-exposure classification was developed to classify women and their husbands according to possible occupational exposures on the basis of their occupational title and industry. RESULTS: In 10% of the pregnancies, the husband was exposed to one or more of the mutagens, and the rate of spontaneous abortion was unaffected (OR = 1.0). Of the 25 specific mutagenic exposures evaluated, paternal exposure to four (ethylene oxide, rubber chemicals, solvents used in refineries, and solvents used in the manufacturing of rubber products) was associated with an increased relative risk of spontaneous abortion. In addition, the risk of spontaneous abortion was higher among wives of rubber products workers than among unexposed men. CONCLUSIONS: Although there is some biological rationale for the findings of this study, these findings need to be confirmed by studies in which individual exposures can be measured directly. PMID- 1853995 TI - The health hazards of saunas and spas and how to minimize them. AB - BACKGROUND: The rapidly increasing number of spas, hot tubs, and saunas intensifies the potentials for deaths from hyperthermia and drowning. METHODS: I analyzed 54 such deaths reported to me by 55 medical examiners and coroners in the United States and 104 deaths reported to the US Consumer Product Safety Commission (CPSC). RESULTS: Only seven of the 158 deaths analyzed occurred in saunas. All of the remaining deaths occurred in spas, jacuzzis, or hot tubs, which were far more numerous. The chief risk factors identified were alcohol ingestion, heart disease, seizure disorders, and cocaine ingestion (alone or in combination with alcohol ingestion). These factors accounted for 71 or 44.7% of the 159 fatalities. Of these risk factors, alcohol represented 38%; heart disease, 31%; seizure disorders, 17%; and cocaine ingestion, alone or in combination with alcohol, 14%. Sixty-one of the 151 spa-associated deaths occurred in children under 12 years of age. Accidental drownings from uncovered or improperly covered spas and, to a lesser extent, entrapment by suction, were the chief causes of childhood drownings. CONCLUSIONS: Children and older persons who have heart disease or seizure disorders or who use alcohol or cocaine are especially vulnerable. Recommended preventive measures include shortening the time of exposure, lowering the temperature, establishing safety standards for covers and for baffles for suction outlets, and using warning notices. PMID- 1853996 TI - Serum total cholesterol: HDL cholesterol ratios in US white and black adults by selected demographic and socioeconomic variables (HANES II). AB - BACKGROUND: Framingham Study findings suggest that total cholesterol (TC):High density lipoprotein cholesterol (HDL-C) ratio is a useful summary of the joint contribution of TC and HDL-C to coronary heart disease (CHD) risk. Information on the distribution of TC:HDL-C in the US population is limited to selected populations and the relationship of the ratio distribution and its correlates has received little attention. METHOD: TC/HDL-C ratios were examined in a representative sample of the United States adult population ages 20 to 74 years, between February 1976 and February 1980 during NHANES II, using stratification and multivariate regression analyses. RESULTS: Age-adjusted mean ratios were higher in men compared with women and were higher in Whites compared with Blacks. White men had the highest TC/HDL-C mean ratios. These relationships remained after stratification by age, education, body mass index, alcohol use, cigarette smoking, and physical activity. Using multivariate analyses, the ratios were positively related to BMI, age, and smoking; and negatively related to female sex, alcohol use, being Black, and physical activity. CONCLUSIONS: Using a ratio reference point of greater than or equal to 4.5 from the Framingham study, at least an estimated 44 million persons ages 25 to 74 years in the US were found to be at higher risk of developing coronary heart disease. PMID- 1853997 TI - Physicians promoting bicycle helmets for children: a randomized trial. AB - Head injury is the leading cause of death and serious morbidity in bicycle accidents. There is good evidence to recommend helmets, yet few children wear them. We evaluated helmet promotion in a randomized trial targeting children presenting to primary care settings for routine ambulatory care. The intervention consisted of physician counseling and take-home pamphlets. The study involved 339 families, 167 in the intervention group and 172 in the control group. In a follow up telephone call, 2 to 3 weeks later, only 7.2% of the intervention group had purchased helmets, compared with 7.0% of the control group (chi 2 = 0.0056, P = .94). During the latter half of the study, bicycle safety received considerable media attention in Ottawa, and the provincial medical society sponsored a $5 discount campaign. Therefore both groups were subject to community "co intervention." Nonetheless, we were surprised that physician counseling made no additional impact. Our results and the success of certain community programs suggest that physicians interested in helmet promotion would do better to participate in the design and implementation of multidisciplinary campaigns. PMID- 1853998 TI - Preventing and postponing death: trends in Tennessee infant mortality. AB - Infants born in Tennessee between 1984 and 1988 experienced reduced mortality compared with those born in the 5 years previous. For all birthweight singleton infants, the reduction from 10.2 to 8.4 deaths per 1000 live births represents an 18% decline in mortality. The most impressive gain made was for very low birthweight (less than 1500 g) infants in the neonatal period, where mortality was reduced 24%. However, for these infants there was nearly a sixfold increase in the postneonatal mortality associated with prematurity-related causes. PMID- 1853999 TI - A comparison of breast-feeding data from the National Surveys of Family Growth and the Ross Laboratories Mothers Surveys. AB - This study compares rates of breast feeding reported in the National Surveys of Family Growth with those from the Ross Laboratories Mothers Surveys. Both surveys have documented rates of breast feeding over the last 30 or more years. Despite differences in survey methodology, both surveys document similar long-term trends in breast feeding. The similarities of rates in breast feeding also are evident across several maternal sociodemographic characteristics. We conclude that both surveys produce reliable and useful estimates of breast feeding. PMID- 1854000 TI - Risk factors for childhood homicides in Ohio: a birth certificate-based case control study. AB - Death certificate of children less than 8 years of age who were killed between 1979 and 1986 were linked to their Ohio birth certificates and compared with those of Ohio children born in 1983 (controls). Having an unmarried mother increased risk of homicide almost fivefold (odds ratio 4.87). Having a teenage mother, a mother who had not graduated from high-school, and being of Black race or low birthweight each increased the risk by approximately threefold. Increases in the proportion of children born to unmarried mothers may contribute to increases in childhood homicide rates. PMID- 1854001 TI - Costs and benefits of implementing child survival services at a private mining company in Peru. AB - Costs and savings of child health services were studied in a private mining company in Peru. Despite considerable outlays for medical services, few children under age 5 were vaccinated, and half of their illnesses went untreated. Children who were attended at the company clinic usually received unnecessary medication. As a result of the study, the company hired additional staff to provide integrated maternal-child preventive health care and family planning and contracted for intensive training and periodic on-site supervision. In less than 2 years, vaccination coverage reached 75%, and virtually all children under age 1 were enrolled in growth monitoring. Prescriptions were reduced by 24%, including a 67% drop in antimicrobials. The cost of the new services was $13,200 for the first 2 years. Approximately $6800 has been saved in pharmaceuticals prescribed for respiratory infection and diarrhea. Recently, two more mines adopted maternal and child health and family planning services. It is hoped that cost-benefit arguments will encourage other companies to incorporate aggressive child survival measures into their health plans. PMID- 1854002 TI - Measles vaccination coverage among Latino children aged 12 to 59 months in Los Angeles County: a household survey. AB - A high rate of measles transmission has occurred in Los Angeles County since 1987. To determine measles vaccination coverage among Latino preschoolers, the group at highest risk of measles during this period, a cluster survey was conducted among Latino households with children aged 12 to 59 months. Of 279 children enrolled, 240 (86%, 95% confidence interval = 81% to 91%) reportedly had received the measles vaccine. Measles vaccination coverage among Latino preschoolers in Los Angeles County is insufficient to halt measles transmission within this subpopulation. PMID- 1854003 TI - Low-level air pollution and upper respiratory infections in children. AB - Effects of low-level air pollution were studied in one polluted city and two reference cities in northern Finland by comparing the frequency of upper respiratory infections over a 12-month period in 1982 as reported by parents of children ages 14 through 18 months (n = 679) and 6 years (n = 759). A similar comparison was carried out between children living in the more polluted and less polluted areas of the polluted city. The annual mean and the greatest half-hour concentrations of sulfur dioxide (23 and 807 micrograms/m3), particulates (31 and 291 micrograms/m3), nitrogen oxides (15 and 160 micrograms/m3), and hydrogen sulfide (2 and 177 micrograms/m3) in the polluted city were mainly due to industrial sources. In the reference cities, air pollution was produced mainly by traffic and heating. Adjusted odds ratios (OR) for one or more upper respiratory infections of residents in the polluted city vs those in the reference cities were 2.0 (95% confidence interval [CI] = 1.3-3.2) in the younger age group and 1.6 (95% CI = 1.1-2.1) in the older age group. Within the polluted city, OR calculated for living in more vs less polluted areas were 2.0 (95% CI = 1.0-4.0) in the younger and 1.6 (95% CI = 1.0-2.7) in the older children. The present results suggests that, for children, air pollution can be hazardous in concentrations lower than those recorded in earlier studies from Britain and central Europe. The synergistic effect of sulfur dioxide, particulates, nitrogen oxides, hydrogen sulfide, and other pollutants may be a contributing factor. PMID- 1854004 TI - Decline in the use of illicit drugs by high school students in New York State: a comparison with national data. AB - A school-based epidemiological survey of the use of drugs was carried out in Spring 1988 among 7,611 adolescents representative of students in grades 7 through 12 in New York State public and private schools. This survey provides the most recent data on the use of crack in that population. Comparison with a statewide survey carried out five years earlier reveals a large decline in the use of illicit drugs in that period. This decline appears to be stronger than the decline reported for national samples. PMID- 1854005 TI - Surveillance of attempted suicide among adolescents in Oregon, 1988. AB - In January 1988, Oregon became the first state to require hospital-based reporting of attempted suicide (AS) in all adolescents less than 18 years old. From January to December 1988, 644 cases of AS were reported (annual rate of 214 per 100,000 population, ages 10 to 17 years). We compared these 644 cases of AS with all 137 Oregon adolescents less than 18 years old who committed suicide in Oregon during the 10-year-period 1979 through 1988, and found that the strongest predictor of outcome was method used. PMID- 1854006 TI - Knowledge of diagnosis and reproductive history among survivors of childhood plumbism. AB - As part of a study of the long-term consequences of childhood plumbism, 35 survivors of lead poisoning in the period 1930 through 1944 were interviewed along with 22 controls matched for age, sex, and town of residence. Subjects were asked to recall all pregnancies they engendered (men) or carried (women), outcome, and intellectual development of resulting children. Matched female plumbism subjects reported a higher proportion of spontaneous abortion or stillbirths among pregnancies (relative risk = 1.60, 95% confidence interval [CI] = 0.6-4.0) and a higher proportion of learning disabilities among school-age children (relative risk = 3.0, 95% CI = 0.9-10.2) in comparison with their controls. There was no evidence of clustering of learning disabilities within families or confounding by parental educational level. These results suggest that women with a history of childhood lead poisoning may be at risk for having spontaneous abortions or stillbirths and having children who manifest significant learning disabilities. PMID- 1854007 TI - MOM-mobile brings ultrasounds to moms. PMID- 1854008 TI - Maternal transfers and hospital perinatal mortality rates. PMID- 1854009 TI - Characteristics of infant deaths due to HIV/AIDS. PMID- 1854011 TI - Number of bicycle injuries unrealistic. PMID- 1854010 TI - Crack cocaine, fellatio, and the transmission of HIV. PMID- 1854012 TI - How can physicians get kids to wear bicycle helmets? A prototypic challenge in injury prevention. PMID- 1854013 TI - Adverse working conditions and premature delivery. PMID- 1854014 TI - Service needs of severely disturbed children. AB - BACKGROUND: As one piece of a statewide Children's Mental Health System Analysis conducted in Washington State, the specific service needs of severely emotionally disturbed children were investigated. METHODS: The primary case-workers of 3398 children under the care of the state responded to a survey of the child's treatment history, social and clinical condition, and service needs. Service need data on the 2455 children in the sample who were classifiable as severely emotionally disturbed were examined using log linear analysis. RESULTS: School- and home-based services were frequently reported needs of school-aged children. Adolescent children were reported to be in need of services which prepare them for adulthood. Services endorsed for female children tended to focus on assistance to family members, therapy, and protection, whereas services endorsed for male children focused on home removal, substance abuse treatment, and preparation for employment. CONCLUSIONS: Severely emotionally disturbed children are in need of a variety of nontraditional mental health services. Significant differences in the needs of male versus female children, and of differently aged children, are present that have serious implications for service system development. PMID- 1854015 TI - Analysis of US child care safety regulations. AB - BACKGROUND: With 1.9 million US children cared for in organized group child care, the safety of these children is a public health concern. In the absence of federal policy, each state has developed its own day care safety regulations. METHODS: After creating a set of 36 criteria from three sets of national guidelines, we assessed the safety regulations of 45 states. With a mailed survey of state day care regulatory personnel, we examined the processes of formulating and implementing safety policy in 47 states. RESULTS: For 24 of the 36 items, more than half the states' regulations were below the criteria or failed to mention the topic. Most notable is the inattention to playground safety, choking hazards, and firearms. CONCLUSION: The uneven quality of regulations may be a reflection of a regulatory process that is fragmented, with many different groups sharing authority and with limited involvement of injury prevention specialists. PMID- 1854016 TI - Promoting physical activity and a healthful diet among children: results of a school-based intervention study. AB - BACKGROUND: National health objectives call for improved diet and more regular physical activity among children. We tested the effects of a school-based program to improve students' diet and physical activity behavior at school. METHODS: Two of the four elementary schools in one Texas school district were assigned to intervention and two to control conditions. The three intervention components were classroom health education, vigorous physical education, and lower fat, lower sodium school lunches. Nutrients from school lunches and the total day and the amount of physical activity students obtained during physical education were assessed as outcome. RESULTS: Analysis of school lunches showed declines from base line to posttest in the two intervention schools of 15.5% and 10.4% for total fat, 31.7% and 18.8% for saturated fat, and 40.2% and 53.6% for sodium; posttest values were lower in the intervention schools. Observation of physical activity during physical education classes indicated an increase in the intervention schools from baseline to posttest in the percent of time children engaged in moderate-to-vigorous physical activity from less than 10% of class time at baseline to about 40% of class time at posttest; posttest values were higher in the intervention schools than in the control schools. CONCLUSIONS: This efficacy study demonstrates the feasibility of substantially modifying school lunches and school physical education to improve children's diet and physical activity behavior at school. PMID- 1854017 TI - Attitudes toward abortion among parents of children with cystic fibrosis. AB - BACKGROUND: DNA prenatal diagnosis for cystic fibrosis (CF) has been available for parents of affected children since late 1985. METHODS: Using anonymous questionnaires, we surveyed 395 parents of children with CF at 12 New England CF centers with regard to 12 maternal or family situations and 11 fetal characteristics; 271 (68%) responded. RESULTS: The majority supported legal abortion in the first trimester for all 23 situations; 58% would abort for severe mental retardation (MR), 40% would abort for a genetic disorder leading to death before age five years, 41% for a child bedridden for life, 35% for moderate MR, 20% for CF and 17% for a severe incurable disorder starting at age 40 years. Few would abort for a disorder starting at age 60 years, for genetic susceptibility to alcoholism or for sex selection. Variables most strongly related to abortion for CF were attitudes of spouse, respondent's siblings, and CF doctor toward abortion for CF as well as infrequent attendance at religious services. CONCLUSIONS: Prenatal diagnosis may not reduce substantially the number of CF births to parents of CF children because most do not accept abortion for CF. PMID- 1854018 TI - Infant diet and salmonellosis. AB - BACKGROUND: The Island of Guam has experienced a high incidence of infant salmonellosis for a number of years (age-specific incidence rate of approximately 3700 cases per 100,000 infants in 1984). Interviews of case parents suggested that the use of high-iron infant formula was associated with this problem. METHODS: A case-control study was conducted to test this hypothesis. Information on feeding practices and a variety of medical and socioeconomic factors was collected for 78 laboratory-confirmed Salmonella-case infants and 167 control infants. RESULTS: Case infants were less likely to have been breast-fed (odds ratio [OR] = 9.15; 95% confidence interval [CI] = 2.71-30.9) and more likely to have been fed infant formula with an iron content of 10 mg/L or greater (OR = 2.96; 95% CI = 1.24-7.08) than were control infants. CONCLUSIONS: Although the precise means by which infants are most commonly exposed to Salmonella bacteria remain obscure, breast-feeding apparently protects against the development of physician-diagnosed clinical salmonellosis, while the feeding of high-iron infant formula has the opposite effect. PMID- 1854019 TI - Use of ion-selective electrodes in kinetic flow injection: determination of phenolic and hydrazino drugs with 1-fluoro-2,4-dinitrobenzene using a fluoride selective electrode. AB - A flow injection (FI) kinetic potentiometric method for the determination of phenolic (acetaminophen and isoxsuprine) and hydrazino (isoniazid) drugs is described. This work shows the usefulness of ion-selective electrodes as detectors in FI systems, not only for direct ion determination but also in routine kinetic analysis. The method is based on the reaction of 1-fluoro-2,4 dinitrobenzene (FDNB) with the analytes in a weakly alkaline medium, which proceeds through the liberation of fluoride from the reagent. The slow reactions with phenols are catalysed by micelles of cetyltrimethylammonium bromide. The reaction rate is monitored with a fluoride-selective electrode in a wall-jet configuration and is used to construct a calibration graph of antilog(delta E/S) 1 versus c (where E = potential, s = slope of the electrode and c = concentration), using the fixed-time approach. The response time and the long term stability of the electrode were found to be adequate for such kinetic determinations. The proposed method overcomes problems associated with end-point spectrophotometric methods using FDNB and allows measurements in highly coloured or turbid solutions. The optimized method has a linear concentration range of 1 x 10(-4)-50 x 10(-4) mol dm-3, a measurement throughput of 20 or 40 per hour and the precision ranges from 1.8 to 3.6% relative standard deviation (n = 3). Results obtained for commercial pharmaceutical formulations compare favourably with those given by reference methods. PMID- 1854020 TI - Amitriptyline-selective plastic membrane sensors and their pharmaceutical applications. AB - The construction and general performance characteristics of potentiometric amitriptyline-plastic membrane sensors, based on ion-pair complexes with triphenylstilbenylborate and tetra(2-chlorophenyl)borate, respectively, are described. Both electrodes show near-Nernstian responses over the range 1 x 10( 2)-7 x 10(-6) mol dm-3 with a detection limit of about 5 x 10(-6) mol dm-3. The electrodes proved useful in the determination of amitriptyline hydrochloride in pure drug substances and pharmaceutical preparations. They were also applied to the determination of content uniformity and dissolution rate of sugar-coated amitriptyline tablets. The physical processes were numerically simulated by typical equations. PMID- 1854021 TI - Simplified method for the determination of organochlorine pesticides in honey. AB - A method is described for the detection and quantitative determination of organochlorine pesticides in honey. After extraction with hexane, the pesticides were cleaned-up by adsorption chromatography on a Florisil Sep-Pak cartridge and eluted with 15% diethyl ether in hexane. The detection of organochlorine pesticides was performed by capillary gas chromatography with electron-capture detection. The quantification limit obtained for different pesticides ranged from 0.56 to 2.78 micrograms kg-1 and recoveries from fortified honey samples averaged 89.6%. PMID- 1854022 TI - Spectrofluorimetric determination of 5-hydroxyindoles with benzylamine or 3,4 dimethoxybenzylamine as a selective fluorogenic reagent. AB - A spectrofluorimetric method has been developed for the sensitive and selective determination of 5-hydroxyindoles; the method is based on the reaction of 5 hydroxyindoles in a weakly alkaline solution (pH 9.0) with aromatic methylamines in the presence of potassium hexacyanoferrate(III) and dimethyl sulphoxide; the compounds produced fluoresce intensely in an alkaline solution (pH 11-12). Of the eight aromatic methylamines tested, benzylamine and 3,4-dimethoxybenzylamine were found to be the most favourable fluorogenic reagents in terms of sensitivity and reactivity. The methods with benzylamine and 3,4-dimethoxybenzylamine permit the determination of 5-hydroxyindoles at concentrations as low as 22-72 pmol ml-1 and 1.0-2.4 nmol ml-1, respectively. PMID- 1854023 TI - High-pressure flow-injection assembly. Indirect determination of glycine by atomic absorption spectrometry. AB - A procedure for the determination of glycine is described. The method is based on the reaction of the analyte with finely powdered, solid copper(II) carbonate in a continuous-flow assembly. The optimum experimental conditions of pH, temperature, sample volume, flow-rate, column length and internal diameter, and the linear range of calibration, were studied. Interference from foreign substances that accompany this amino acid in pharmaceutical formulations was studied, and the method was applied to the determination of glycine. PMID- 1854024 TI - Perioperative maternal and neonatal acid-base status and glucose metabolism in patients with insulin-dependent diabetes mellitus. AB - Maternal and neonatal acid-base status and glucose metabolism were studied in 20 patients with insulin-dependent diabetes mellitus (group 1) undergoing elective cesarean section under lumbar epidural anesthesia. All patients were given glucose/insulin infusion before delivery. Fifteen healthy patients with iatrogenic hyperglycemia (group 2) and 15 healthy euglycemic patients (group 3) served as controls. Results were expressed as mean +/- 1 SE and were analyzed using analysis of variance and chi 2 analysis at P less than 0.05. No significant differences were seen at delivery either in maternal arterial and neonatal umbilical venous and arterial blood acid-base status or in neonatal Apgar scores among the three groups. Patients in groups 1 and 2 had larger blood glucose concentrations than those in group 3 (P = 0.01). Diabetic mothers and their neonates had a 25%-50% reduction in pyruvate concentration in maternal venous, and neonatal umbilical venous and arterial blood compared with that in the other two groups (P = 0.001). Postpartum neonatal hypoglycemia (less than 30 mg/dL) developed in seven of the group 1 neonates (P = 0.05). Thus, epidural anesthesia in diabetic women is associated with normal acid-base status in the mother and in the neonate. The data also show an increased incidence of neonatal hypoglycemia and altered maternal and neonatal glycolysis in patients with diabetes mellitus. PMID- 1854025 TI - Effect of intravenously administered dexmedetomidine on pain after laparoscopic tubal ligation. AB - Ninety-six women undergoing laparoscopic tubal ligation were randomized to receive intravenously either 0.2 or 0.4 microgram/kg of dexmedetomidine, 60 micrograms/kg of oxycodone, or 250 micrograms/kg of diclofenac for postoperative pain in a double-blind study design. The study drugs were administered in the recovery room for moderate or severe pain and were repeated until pain subsided or disappeared. In the group receiving diclofenac, 83% of the patients required analgesic supplementation with morphine. This contrasted (P less than 0.01) with 33% of the patients receiving either oxycodone or the higher dose of dexmedetomidine. After the first dose of oxycodone was injected, the visual analogue scale for pain (0%-100%) was reduced from 58% to 33%, whereas corresponding pain relief was only achieved after the third injection of 0.4 microgram/kg of dexmedetomidine. Repeated doses of 0.2 microgram/kg of diclofenac or dexmedetomidine did not reduce the visual analogue scale value by more than 17%. More sedation was seen with the higher dose of dexmedetomidine than with either diclofenac or oxycodone (P less than 0.001). Both doses of dexmedetomidine decreased heart rate when compared with diclofenac (P less than 0.001). In the group given 0.4 microgram/kg of dexmedetomidine, 33% of the patients required atropine for bradycardia. The authors conclude that after laparoscopic tubal ligation, intravenously administered dexmedetomidine relieves pain and reduces opioid drug requirement but is attended by sedation and a high incidence of bradycardia. PMID- 1854026 TI - Effect of prior anesthetic solution on epidural morphine analgesia. AB - The quality and duration of analgesia and incidence of side effects following epidurally administered morphine after cesarean section are highly variable. Two suggested sources of this variability are prior use of epinephrine-containing solutions, which may enhance both analgesia and side effects of morphine, and prior use of 2-chloroprocaine, which may inhibit epidural morphine analgesia. To examine these proposed sources of this variability we performed two studies. In the first, designed to test epinephrine's effect, 30 women underwent testing for epidural catheter tip location with injection of 2-chloroprocaine, followed by either 0.5% bupivacaine alone or 0.5% bupivacaine with 5 micrograms/mL epinephrine for epidural anesthesia. Inclusion of epinephrine with bupivacaine decreased the bupivacaine dose needed to achieve a T-4 sensory block by 24% (P less than 0.05), but did not alter analgesic duration or the incidence of side effects of epidural morphine (5 mg). In the second study, designed to test the effect of 2-chloroprocaine, 30 women received 7 mL of either 2% 2-chloroprocaine or lidocaine for epidural catheter testing, followed by 0.5% bupivacaine for epidural anesthesia. Compared to lidocaine testing, 2-chloroprocaine decreased the duration of epidural morphine analgesia (median 16 h with 2-chloroprocaine vs 24 h with lidocaine; P less than 0.05) without altering the incidence of side effects. The authors conclude that addition of epinephrine to local anesthetic does not increase the incidence of side effects or the analgesic effect from epidurally administered morphine. 2-Chloroprocaine, even when administered in small doses remote to the time of morphine injection, interferes with the duration of epidural morphine analgesia. PMID- 1854027 TI - Comparison of continuous epidural bupivacaine infusion plus either continuous epidural infusion or patient-controlled epidural injection of fentanyl for postoperative analgesia. AB - We compared the postoperative epidural analgesia provided by the continuous epidural infusion of bupivacaine supplemented with patient-controlled injection (PCA) of epidural fentanyl with that provided by a continuous infusion of bupivacaine supplemented with a continuous epidural infusion of fentanyl. Our patient population comprised 16 ASA physical status I or II patients undergoing laparotomy with a midline incision under general anesthesia combined with bupivacaine epidural analgesia. Post-operatively, a continuous epidural infusion of bupivacaine (0.1 mg.kg-1.h-1) was combined with epidural fentanyl given by either (a) PCA (15-micrograms bolus with a lockout interval of 12 min, n = 8) or (b) continuous infusion (1 microgram.kg-1.h-1, n = 8). In the case of inadequate pain relief in the latter group, the fentanyl infusion rate was increased by 10 micrograms/h. Analgesia evaluated by a visual analogue pain score and by a verbal pain score was similarly effective in both groups. The sedation score was also similar in both groups. The total dose of epidural fentanyl administered during the first 24 h was significantly lower in the PCA group than in the continuous infusion group (405 +/- 110 micrograms vs 1600 +/- 245 micrograms, P less than 0.001). The dose of fentanyl given during each 4-h interval ranged between 40 and 160 micrograms in the PCA group and 251 and 292 micrograms in the continuous infusion group. Clinically detectable respiratory depression was not observed in either group. In conclusion, epidural administration of 0.1 mg.kg-1.h-1 bupivacaine combined with fentanyl provides effective postoperative analgesia with a total dose of fentanyl required that is lower when fentanyl is administered by epidural PCA rather than by continuous epidural infusion. PMID- 1854028 TI - Can galvanic skin response be used as a quantitative estimate of sympathetic nerve activity in regional anesthesia? AB - To study the relationship between skin sympathetic nerve activity and changes in skin resistance (galvanic skin response--GSR), efferent sympathetic and sensory nerves to the hand were blocked by an axillary nerve blockade in 15 healthy subjects. Subsequently, intraneural electrical stimuli in the median nerve distal to the axillary nerve block were used to evoke changes in skin resistance and in water vapor partial pressure in the sensory and sympathetically denervated hand. With increasing frequency of stimulation, skin resistance decreased and water vapor partial pressure increased until stimuli exceeded 10 Hz. When an additional burst of impulses was added to the background stimulation, GSR amplitude varied in a nonlinear fashion with the background frequency. Stimulation-induced GSR was completely abolished in a dose-dependent manner by systemically (intravenously) administered atropine. The results indicate that GSR depends on the preceding level of nerve traffic in the sympathetic sudomotor nerve fibers. Consequently, skin resistance recordings cannot be used to quantify sympathetic nerve traffic and thus do not express the completeness of sympathetic blockade in regional anesthesia. PMID- 1854029 TI - Cardiovascular actions of desflurane in normocarbic volunteers. AB - The cardiovascular actions of three concentrations of desflurane (formerly I 653), a new inhalation anesthetic, were examined in 12 unmedicated normocapnic, normothermic male volunteers. We compared the effects of 0.83, 1.24, and 1.66 MAC desflurane with measurements obtained while the same men were conscious. Desflurane caused a dose-dependent increase in right-heart filling pressure and a decrease in systemic vascular resistance and mean systemic arterial blood pressure. As measured by echocardiography, left ventricular end-diastolic area did not change except for a small increase at 1.66 MAC desflurane, and systolic wall stress was less at all concentrations of desflurane than during the conscious state. Desflurane did not change cardiac index or left ventricular ejection fraction. Heart rate did not change at 0.83 MAC, but progressively increased with deeper desflurane anesthesia. Stroke volume index was less at all concentrations of desflurane than while the men were conscious, but desflurane did not alter the velocity of ventricular circumferential fiber shortening. Mixed venous blood PO2 and oxyhemoglobin saturation were higher during all concentrations of desflurane anesthesia than during the conscious state. No volunteer developed a metabolic acidosis. We conclude that desflurane with controlled ventilation and constant PaCO2 causes cardiovascular depression, as indicated by the increased cardiac filling pressure and decreased stroke volume index and by no change in the velocity of circumferential fiber shortening in the presence of decreased systolic wall stress. However, cardiac output is well maintained, and heart rate does not increase at light levels of anesthesia. The cardiovascular actions of 0.83 and 1.66 MAC desflurane were also reexamined in 6 of the 12 men during the seventh hour of anesthesia. Prolonged desflurane anesthesia resulted in lesser cardiovascular depression than was evidenced during the first 90 min. The measures of cardiac filling (central venous pressure and left ventricular end-diastolic cross-sectional area) did not differ between the early and late periods of anesthesia. Systemic vascular resistance decreased further during the late period, but systolic wall stress did not differ between the two time periods. During the seventh hour of desflurane anesthesia, heart rate and cardiac index were higher at both anesthetic concentrations than during the first 90 min of anesthesia. Left ventricular ejection fraction and velocity of fiber shortening did not change with duration of desflurane anesthesia. Oxygen consumption, oxygen transport, the ratio of the two, mixed venous PO2, and mixed venous oxyhemoglobin saturation (SO2) increased late in the anesthetic in comparison with the first 90 min. PMID- 1854030 TI - Hemodynamic effects of desflurane/nitrous oxide anesthesia in volunteers. AB - We determined the cardiovascular effects of 0.91, 1.34, and 1.74 MAC of desflurane/nitrous oxide anesthesia (60% inspired nitrous oxide contributed 0.5 MAC at each level) in 12 healthy, normocapnic male volunteers. Desflurane/nitrous oxide anesthesia decreased systemic blood pressures, cardiac index, stroke volume index, systemic vascular resistance, and left ventricular stroke work index, and increased pulmonary arterial pressures and central venous pressure in a dose dependent fashion, while heart rate was 10%-12% and mixed venous oxygen tension was 2-4 mm Hg higher at all MAC levels than at baseline (awake). Desflurane/nitrous oxide anesthesia modestly increased left ventricular end diastolic cross-sectional area (preload) and decreased velocity of left ventricular circumferential fiber shortening, systolic wall stress (afterload), and area ejection fraction; this combination of changes indicates myocardial depression. At approximately comparable MAC levels, heart rate was lower and systemic blood pressures, central venous pressure, left ventricular stroke work index, and systemic vascular resistance usually were significantly higher during anesthesia with desflurane and nitrous oxide than during desflurane anesthesia alone (same volunteers, data collected in crossover design). After 7 h of anesthesia, regardless of the background gas, somewhat less cardiovascular depression and/or modest stimulation was apparent: cardiac index, area ejection fraction, and velocity of left ventricular circumferential fiber shortening recovered to or toward awake values, whereas heart rate was further increased. Evidence of circulatory insufficiency did not develop in any volunteers during the study. Segmental left ventricular function was normal at baseline, and no segmental wall-motion abnormalities, ST-segment change, or dysrhythmias developed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854031 TI - Cardiovascular actions of desflurane with and without nitrous oxide during spontaneous ventilation in humans. AB - We investigated the cardiovascular actions of desflurane (formerly I-653) during spontaneous ventilation. We gave 0.8-0.9, 1.2-1.3, and 1.6-1.7 MAC desflurane in oxygen (n = 6) and in 60% nitrous oxide, balance oxygen (n = 6) to unmedicated healthy male volunteers. Both anesthetic regimens decreased ventilation, increased partial pressure of arterial carbon dioxide, and produced similar cardiovascular changes. In comparison with values obtained when the volunteers were conscious, desflurane anesthesia with spontaneous ventilation decreased systemic vascular resistance and mean arterial blood pressure. Cardiac index, heart rate, stroke volume index, and central venous blood pressure increased. Left ventricular ejection fraction increased at 0.83 MAC desflurane in oxygen, and otherwise did not differ from the conscious value. The velocity of ventricular circumferential fiber shortening, estimated by echocardiography, increased with desflurane in oxygen but did not change with desflurane in nitrous oxide. Oxygen consumption increased during desflurane and oxygen anesthesia, but not when nitrous oxide plus oxygen was the background gas. Desflurane increased oxygen transport, the ratio of oxygen transport to oxygen consumption, mixed venous partial pressure of oxygen, and oxyhemoglobin saturation. The cardiovascular changes with desflurane during spontaneous ventilation differ from those during controlled ventilation. With both background gases, spontaneous ventilation, in comparison with controlled ventilation, increased cardiac index, stroke volume, central venous pressure, left ventricular ejection fraction, velocity of circumferential fiber shortening, oxygen transport, and the ratio of oxygen transport to oxygen consumption but did not change mean arterial blood pressure except at 1.66 MAC desflurane in oxygen (when it was higher with spontaneous than with controlled ventilation). PMID- 1854032 TI - Does desflurane modify circulatory responses to stimulation in humans? AB - We asked if desflurane with or without nitrous oxide at 0.83, 1.24, and 1.66 MAC prevented cardiovascular responses to stimulation. We measured cardiac output, heart rate, systemic arterial blood pressure, central venous pressure, pulmonary arterial blood pressure, and systemic vascular resistance in six healthy male volunteers before (control) and at 0, 1, 2, 4, and 6 min after tetanic electrical stimulation (50, 100, and 200 Hz) of the ulnar nerve. At 0.83 and 1.24 MAC, cardiac output, mean systemic arterial blood pressure, heart rate, and pulmonary arterial blood pressure increased. Peak changes averaged 13%-20% and most frequently occurred 0-2 min after stimulation (P less than 0.05) with return to control values at 4-6 min (except for pulmonary arterial blood pressure). At 1.66 MAC, heart rate and systemic blood pressure responses were attenuated, but this level of anesthesia had equivocal effects on the cardiac output and pulmonary blood pressure responses. The addition of nitrous oxide attenuated the peak response of heart rate and cardiac output but not the peak response of mean systemic arterial blood pressure. In summary, 0.83 and 1.24 MAC desflurane did not abolish cardiovascular responses to stimulation, but 1.66 MAC attenuated the responses. PMID- 1854033 TI - Fluoride metabolites after prolonged exposure of volunteers and patients to desflurane. AB - We examined the metabolism of desflurane in 13 healthy volunteers given 7.35 +/- 0.81 MAC-hours (mean +/- SD) of desflurane and 26 surgical patients given 3.08 +/ 1.84 MAC-hours (mean +/- SD). Markers of desflurane metabolism included fluoride ion measured via an ion-specific electrode, nonvolatile organic fluoride measured after sodium fusion of urine samples, and trifluoroacetic acid determined by a gas chromatographic-mass spectrometric method. In both volunteer and patient groups, postanesthesia serum fluoride ion concentrations did not differ from background fluoride ion concentrations. Similarly, postanesthesia urinary excretion of fluoride ion and organic fluoride in volunteers was comparable to preanesthesia excretion rates. However, small but significant levels of trifluoroacetic acid were found in both serum and urine from volunteers after exposure to desflurane. A peak serum concentration of 0.38 +/- 0.17 mumol/L of trifluoroacetic acid and a peak urinary excretion rate of 0.169 +/- 0.107 mumol/h were detected in volunteers at 24 h after desflurane exposure. Although these increases in trifluoroacetic acid after exposure to desflurane were statistically significant, they are approximately 10-fold less than levels seen after exposure to isoflurane. Thus, desflurane strongly resists biodegradation, but a small amount is metabolized in humans. PMID- 1854034 TI - A survey of 800 patients' knowledge, attitudes, and concerns regarding anesthesia. AB - The present study was undertaken to assess patients' knowledge, attitudes, and concerns regarding anesthetic management. A survey of 34 items was developed and administered preoperatively to 800 consecutive patients. Included were 303 men and 497 women with a mean age 52 yr and a mean educational level of 12 yr. Patients were interviewed on their knowledge of the role and training of anesthesiologists and on their preferences regarding anesthetic management. Patients also rated the intensity of their concern on 20 written statements expressing potential anesthetic complications. Results indicated that patients' perceptions of the anesthesiologist's training and role were accurate. Most patients preferred (a) general to regional anesthesia and (b) not to select their own anesthesiologist. Most significant preoperative concerns regarding the anesthesiologist focused on experience, qualifications, and presence or absence during the anesthesia. Patient concerns also included the possibility of not waking up postoperatively, experiencing pain, and becoming paralyzed. Intensity of concern was inversely related to age and unrelated to educational level or occupation. Variables related to type of concern included patient's sex, type of anesthesia, and proposed surgical procedure. Issues of least concern included disclosure of personal matters during anesthesia, experiencing impaired judgment postoperatively, and being asleep or bedridden for a prolonged period of time. It is suggested that anesthesiologists address significant patient concerns during the preoperative visit to enhance their effectiveness in patient care. Efforts to educate the public on the anesthesiologist's role in perioperative care should improve patient confidence. PMID- 1854035 TI - Visceral losses of desflurane, isoflurane, and halothane in swine. AB - Percutaneous loss of inhaled anesthetics is small relative to their uptake. The minor nature of this loss results in part from the substantial barrier to diffusion posed by the skin. Pleural and peritoneal surfaces pose less effective barriers because diffusion distances are smaller than in the skin. Accordingly, we measured visceral loss to air of desflurane, isoflurane, and halothane from pleural and peritoneal surfaces in five juvenile swine. Pleural and peritoneal losses per percent end-tidal anesthetic correlated directly with the solubility of the anesthetic in blood or tissues. The total pleural losses for the first 30 min of anesthetic administration were desflurane, 1.22 +/- 0.22 mL (mean +/- standard deviation for the 30-min period); isoflurane, 2.34 +/- 0.52 mL; and halothane, 4.69 +/- 0.98 mL; respective peritoneal losses were 0.64 +/- 0.12 mL, 1.23 +/- 0.25 mL, and 2.69 +/- 0.57 mL. Pleural loss per unit time did not change with increasing duration of anesthesia, whereas peritoneal loss increased for all anesthetics. These visceral losses are greater than total percutaneous losses in humans given these anesthetics for the same period of time, but the loss of anesthetic by either route is too small to affect measurements of anesthetic kinetics or recovery. PMID- 1854036 TI - Simultaneous comparison of intraarterial, oscillometric, and finapres monitoring during anesthesia. AB - In 30 patients (15 with normal peripheral vascular status and 15 with peripheral vascular disease, hypertension, or a heavy smoking history), systolic, mean, and diastolic arterial pressures were recorded simultaneously every 5 min using a radial arterial catheter, an oscillometric arm cuff, and a Finapres finger cuff during 1-6 h of anesthesia and operation. The average accuracy of oscillometric and Finapres pressure measurements was good. Comparisons of arterial, oscillometric, and Finapres pressures showed only a small bias in the oscillometric and Finapres pressure estimations. Finapres pressures underestimated arterial pressures by 1 mm Hg more than oscillometric pressures did. Peripheral vascular status had no effect on comparisons made between pressures measured with these two techniques. Although bias was small, precision was often lacking as shown by the large variability of the difference between individual values from the three monitors. However, the precision of Finapres pressure measurements was about the same order of magnitude as that of oscillometric measurements. PMID- 1854037 TI - Ethical issues in anesthesia: management of the do-not-resuscitate patient. PMID- 1854038 TI - Spinal anesthesia using subcutaneously implanted pumps for intrathecal drug infusion. PMID- 1854039 TI - Prevention of nitrous oxide-induced increases in endotracheal tube cuff pressure. PMID- 1854040 TI - Sensitivity and specificity of tests of malignant hyperthermia susceptibility. PMID- 1854041 TI - Map of contributions to Anesthesiology and Anesthesia and Analgesia. PMID- 1854042 TI - Alternative chin-support device during face mask anesthesia. PMID- 1854043 TI - Bleeding diathesis after perioperative ketorolac. PMID- 1854044 TI - A hidden leak in the circle system. PMID- 1854046 TI - A "new" brachial plexus block: some questions and objections. PMID- 1854045 TI - Additional factor related to suction trauma. PMID- 1854047 TI - [Hemodynamic effects of the induction of general anesthesia after low thoracic epidural anesthesia]. AB - Sixteen ASA 1 or 2 patients scheduled for abdominal surgery were included in the study after they had given their informed consent. Thirty minutes after starting a low-thoracic epidural anaesthesia (median level of sensitivity loss: T5), the patients were randomly given an intravenous bolus injection of either thiopentone (4 mg.kg-1, n = 8) or etomidate (0.5 mg.-1, n = 8), associated with succinylcholine 1 mg.kg-1. One minute after induction of general anaesthesia, the patients were intubated and mechanically ventilated (V(T) 8 ml.kg-1, rate 12 c.min-1). Mean arterial blood pressure (MAP) (oscillometric method), cardiac output (CO) (transthoracic bioimpedance) and heart rate were recorded semi continuously. Total peripheral resistances (TPR) were calculated using the formula TPR = (MA/CO)*80. There were no differences between the groups in patient age, height, weight, and cardiovascular consequences of epidural anaesthesia. After anaesthetic induction and before endotracheal intubation, there was a slight decrease in CO in both groups, without any change in MAP. After intubation, MAP increased in both groups through peripheral vasoconstriction, whereas CO did not increase further. A significant tachycardia was occurred only seen in the thiopentone group, before and after tracheal intubation. This study showed that thiopentone and etomidate were suitable drugs for anaesthetic induction in a patient under epidural blockade. However, the absence of tachycardia following etomidate may be beneficial in cardiac patients. The monitoring of cardiac output determinants during thiopentone and etomidate anaesthesia require further invasive investigations. PMID- 1854048 TI - [Amikacin concentrations in lung and serum after single intratracheal administration in men]. AB - This study was designed to assess the diffusion into lung tissue and systemic circulation of amikacin administered endotracheally. Eleven consecutive patients, suffering from lung carcinoma and scheduled for elective pneumonectomy or lobectomy, were included in the study. After induction of anaesthesia and before tracheal intubation, a single 500 mg amikacin dose was administered endotracheally through a catheter whose tip was located 5 cm below the vocal cords. Blood was then collected every 15 min for serum assays, until pulmonary resection had been carried out. Pulmonary concentrations were assessed in a healthy area. Measurements were carried out in duplicate using fluorescence polarizing immunoassay and microbiological methods. Serum peak concentrations were found 105 min after administration (7.97 +/- 5.62 micrograms.ml-1). Six and 12 h after administration, serum concentrations were 3.19 +/- 1.87 and 1.20 +/- 0.67 micrograms.ml-1 respectively. Mean lung concentrations were 1.85 +/- 2.12 micrograms.g-1, with a corresponding serum level of 7.22 +/- 4.36 micrograms.ml 1. However, endotracheal instillation of amikacin provided serum concentrations which, were not high enough for treatment of gram negative pneumonia. Lung concentrations are lower than both serum levels and MIC90 for gram negative bacilli. Moreover, there was a major heterogeneity in serum and lung levels, which seemed to be unpredictable. This was probably due to heterogenous tracheal, bronchial and alveolar absorption. The results obtained in this study with a single dose administration should be reassessed in the light of data obtained with long-term amikacin administration. PMID- 1854049 TI - [Anesthesia in unilateral pulmonary transplantation]. AB - Single lung transplantation was performed in several steps: laparotomy to prepare an omentopexy, followed by pneumonectomy and implantation of a pulmonary graft, both by postero-lateral thoracotomy. The patients suffered from lymphangiomyomatosis (1), panacinar emphysema (2) and idiopathic pulmonary fibrosis (1). Immunosuppressive treatment was started before surgery. Anaesthesia was induced and maintained with alfentanil, midazolam and vecuronium. The patients were intubated with a Carlens endotracheal tube. Ventilation was carried out using an oxygen-air mixture, without any nitrous oxide or halogenated anaesthetic agent. Besides the usual parameters, expired CO2 concentrations, and oxygen saturation in the pulmonary artery were monitored. Partial femoro-femoral cardiopulmonary bypass was not required. Three major problems were encountered: hypoxia, hypercapnia, and pulmonary arterial hypertension. Hypoxia first occurred during the period of one-lung ventilation, during pneumonectomy, and again after unclamping of the graft vessels before the bronchus had been anastomosed. It was treated either by increasing the FiO2, inflating the lungs with pure oxygen, or partial clamping of the homolateral pulmonary artery. Hypercapnia occurred in three of the four patients until the graft was ventilated again. Except in one patient with preoperative pulmonary hypertension, the increase in pulmonary vascular resistances remained moderate after clamping of the pulmonary artery. Sufficient oxygen delivery, with more than 50% venous oxygen saturation, was maintained at this time by the infusion of dopamine and dobutamine. Two other specific problems were encountered in the emphysematous patients: severe hypotension following the start of artificial ventilation and after placing the patient in lateral position; thoracic asymetry with overdistension of the emphysematous lung, and mediastinal shift.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854050 TI - [Peripheral nerve block during ambulatory surgery of varicose veins]. AB - This retrospective study of the 46 operations, carried out over a one year period for lower limb varicose veins using peripheral nerve blocks, included 45 patients (35 women and 10 men, mean age 49.3 years), all ASA 1 or 2, except for 4 elderly patients with a varicose ulcer (ASA 2 or 3). In 40 procedures, a sciatic nerve block combined with a "3 in 1" lumbar plexus block at the level of the groin (as described by Winnie) were used. In the remaining six, either a sciatic nerve block (short saphenous vein crossectomy; n = 3), or a "3 in 1" lumbar plexus block alone (short stripping of the long saphenous vein; n = 3) were required. A peripheral nerve stimulator to locate accurately each nerve was used. For each nerve block, the anaesthetic mixture consisted of 20 ml lidocaine 1.5% with 1:200,000 adrenaline, and 10 ml of bupivacaine 0.375% with 1:200,000 adrenaline. Surgery was only performed on one limb at a time, as the required dose of local anaesthetic was too high to safely carry out bilateral nerve blocks. In 71.7% of patients surgery was made on an day-case basis. Of those patients who had to remain in hospital overnight or longer, the peripheral nerve block was never responsible for this. During the same period, nine similar procedures were carried out under general anaesthesia, and two under epidural anaesthesia. They included seven bilateral varicose veins, three patient refusals for peripheral nerve blocks, and one allergy to lidocaine. Already used for some procedures in orthopaedic and casualty surgery, peripheral nerve blocks seem to be well suited for surgery of unilateral varicose veins. PMID- 1854051 TI - [Vascular effects of adenosine-triphosphate]. AB - This study assessed the effects of adenosine triphosphate (ATP) on systemic vascular resistances during the hypothermic cardiopulmonary bypass phase of cardiac surgery. Twenty patients scheduled for cardiac surgery were randomly divided into an ATP group (n = 10), and a placebo group (n = 10). Anaesthesia was similar for all the patients (diazepam, fentanyl and pancuronium). During the heart arrest phase, and as soon as the arterial pressure, the level in the venous return reservoir, and the pump flow rate had all been in steady state for 5 min, ATP or placebo was injected into the venous line of the oxygenator. Injection speed was doubled every three minutes, twice. The following ATP doses were administered: 0.012, 0.025 and 0.05 mg.kg-1.min-1. The level in the venous return reservoir was kept constant. Mean arterial pressure (MAP) and pump flow rate (DP) were assessed every half minute. Systemic vascular resistances were calculated with the relationship MAP/DP. Changes in vascular capacitance were directly proportional to changes in DP as the heart had been excluded, and all the blood returned to the pump, the blood volume being kept constant. MAP and DP remained unchanged in the placebo group. In the opposite ATP induced a dose-related systemic vasodilation: MAP decreased from 82.8 +/- 12.5 mmHg (control) to 66.0 +/ 14.8 mmHg, 59.8 +/- 10.6 mmHg, and 49.0 +/- 4.7 mmHg with 0.012, 0.025 and 0.05 mg.kg-1.min-1 ATP respectively. The MAP returned to preinfusion control levels when the ATP infusion was discontinued (90.0 +/- 17.8 mmHg). The DP, and therefore venous return, did not change, neither during ATP infusion, nor after its discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854052 TI - [Comparison of thrombogenic risk between teflon and polyethylene in prolonged catheterization of the radial artery]. AB - This prospective study was designed to compare the rates of radial artery thrombosis after long-term cannulation with two different types of catheters with similar size. It included 101 patients, randomly assigned to group A (n = 51, 61 +/- 17 years, 80% males), and group B (n = 50, 55.8 +/- 18 years, 54% males). Patients in group A were cannulated with a polyethylene catheter (Leader Cath. 115-09), and those in group B with a Teflon catheter (Plastimed Seldicath). The diagnosis of arterial occlusion was made by way of a bedside angiography performed before catheter removal. An X-ray was taken after injection of 10 to 15 ml Hexabrix through the catheter. The two groups were similar with regard to anthropometric parameters (except for the sex ratio), cannulation technique, used drugs, duration of cannulation, pathological events during the stay in intensive care. The rate of complete arterial thrombosis in the two groups was similar (10%). There were no differences in the rates of partial thrombosis (51 vs. 36%, n.s.) and of absence of thrombosis (39 vs. 54%, n.s.). The rate of arterial thrombosis did not vary with the duration of cannulation, nor with age, sex, systemic heparinization, vascular collapse, cannulation technique. However, 4 polyethylene catheters were infected on removal (coagulase negative Staphylococcus, Pseudomonas aeruginosa) versus only one Teflon catheter (Staphylococcus epidermidis). In conclusion, the biocompatibility of Teflon and polyethylene catheters was found to be similar. PMID- 1854053 TI - [Effects of an additional dose of propofol on intraocular pressure in patients over 60 years of age]. AB - Changes in intraocular pressure (IOP) and mean arterial pressure (MAP) were studied in fifty patients, ASA 1 or 2, aged more than 60 years and scheduled for surgery of the anterior chamber of the eye. The exclusion criteria were: arterial hypertension, raised IOP, obesity, renal or hepatic disease, treatment likely to alter IOP, and a possibly difficult intubation. The patients were randomly assigned to groups P1 (n = 25) and P2 (n = 25). All were given lorazepam 1 mg orally 90 min before induction, which was carried out with propofol 1.5 mg.kg-1 and vecuronium 0.1 mg.kg-1. Patients in group P1 were intubated as soon as the train-of-four response (TOF) had been abolished. Those in group P2 were given an additional 0.7 mg.kg-1 dose of propofol before intubation. MAP, heart rate and IOP were measured before and after induction, and 1, 2 and 3 min after intubation. IOP decreased after induction, and remained below the baseline values at all times in both groups. MAP had a similar course in both groups up to 1 min after intubation: a decrease after induction followed by an increase after intubation. In group P1, MAP remained above control values 2 and 3 min after intubation, whereas in P2 it remained below. From this study, it can be concluded that using an additional dose of propofol in elderly patients was not useful for avoiding the rise in IOP due to endotracheal intubation. This was all the more so as the haemodynamic effects of such a dose of propofol could have deleterious effects in these patients. PMID- 1854054 TI - [Effect of the association propofol-alfentanil on bronchial resistances in asthmatic patients]. AB - The bronchial resistances in 17 patients scheduled for ENT surgery were studied during general anaesthesia carried out with propofol and alfentanil. There were nine controls, all free from any allergic pathology. The other eight had bronchial hyperreactivity, with clinical asthma (one or two crises a month) treated with bronchodilators. Two had a complete Fernand-Widal syndrome, and the remaining six documented allergic asthma. All the patients were premedicated with hydroxyzine 2 mg.kg-1 orally on the eve of surgery, and two hours beforehand. Those patients who were on bronchodilators were given their drugs as usual with the premedication. Because bronchial resistances were measured with the patient breathing spontaneously (forced oscillation technique), induction was carried out in two steps, first with propofol 1.5 mg.kg-1, followed, two minutes later, by alfentanil 7 micrograms.kg-1. Once the bronchial resistances had been assessed the patient was given a further 2 mg.kg-1 dose of propofol, and alfentanil 40 micrograms.kg-1. The patient was then intubated, and anaesthesia maintained with propofol 9 mg.kg-1.h-1, and alfentanil 15 micrograms.kg-1 every fifteen minutes. In all, bronchial resistances were measured on the day before surgery, after premedication but before the patient had been given any anaesthetic drug, two minutes after the first injection of propofol, two minutes after the first injection of alfentanil, and after extubation. There were no significant differences between the two groups. Despite the small number of patients included in this study, it would seem that hydroxyzine, propofol and alfentanil may be used safely in patients with hyperreactive bronchi. PMID- 1854055 TI - [Patient-controlled analgesia]. AB - Patient controlled analgesia (PCA) is a drug delivery system aimed to control acute pain using negative feedback technology in a closed loop system in which the patient plays an active role. It overcomes the inadequacies of traditional analgesic protocols due to marked differences in pharmacokinetic and dynamy of analgesis between patients. Moreover, doctors and nurses frequently underprescribe opioids in patients with severe pain for fear of dangerous side effects. A safe and effective delivery of these drugs on patient demand can be achieved using various delivery systems, modes and dosing parameters. Most devices provide both demand dosing, where a constant predetermined dose is self administered, and constant rate infusion plus demand dosing, where the minimum administration rate is determined by the doctor, but can be supplemented by patient demand. Morphine sulphate remains the drug most commonly used in PCA therapy, but meperidine hydrochloride, alfentanil, nalbuphine and buprenorphine are also sometimes administered. The doctor determines the incremental dose per demand, the lockout interval, and the maximum dose per time unit, possibly also the loading dose and the minimum dose rate when a continuous flow is used. PCA provides improved analgesia, which is immediate and independent of nurse availability. This technique decreases opioid requirements, and the required total amounts are lowered. PCA gives patients both behavioural and decisional control. They can titrate the analgesic dose in such a way as to balance pain relief with the degree of side-effects, the patient is willing to tolerate. Patients often choose less than the available total dose of analgesic. The risks consists in the usual opioid side-effects, mainly respiratory depression. These may be due to mechanical problems, machine failure, or user incidents (misprogramming, or miscalculation of doses). Standards help to ensure consistent care and avoid errors that can occur even with handwritten orders. The principles of demand analgesia are now being investigated using other agents, such as local anaesthetics, and other routes of administration, mainly epidural injection. In most patients, even in children, PCA can replace intramuscular injections, which are the standard route for opioid administration. Today PCA and spinal opioids are the two main methods of analgesia for postoperative pain management. PMID- 1854056 TI - [Heparin and spinal or epidural anesthesia: decision analysis]. AB - The incidence of thromboembolism justifies prophylactic measures, the most efficient of which is the use of heparin. However this agent may be responsible for haemorrhagic complications during regional anaesthesia. The risk of bleeding in a poorly accessible area, e.g. the epidural space, the brachial plexus sheet, the space behind the eyeball, is one of the concerns of anaesthetists. A review of case reports of haemorrhagic complications of spinal anaesthesia shows that the risk of bleeding or of spinal haematoma is very low. In fact, a blood or epidural vessel is punctured in 2.8 to 11.5% of cases of epidural anaesthesia, without any sequelae. Some authors suggest that low molecular weight heparin may be given to patients before spinal anaesthesia. In all cases, patients should be carefully assessed before, during and after the procedure, clinically and biologically. The absolute contra-indications to these techniques are a refusal by the patient, an uncooperative patient, severe coagulation disorders, untreated hypovolaemia, infection of the puncture site, severe generalized infection, and raised intracranial pressure. Decision as to whether a regional anaesthetic technique should be used in a particular patient who is under anticoagulant treatment, or who is to receive such a treatment intra or postoperatively, must be made on an individual basis. The risk of thromboembolism must be weighted against the risk of haemorrhagic complications. Unfortunately, in the absence of relevant studies, anaesthetists can only rely on their clinical judgment. PMID- 1854057 TI - [A rare cause of difficult intratracheal intubation: Langenbeck's disease]. AB - A case of difficult tracheal intubation due to insufficient mouth opening once anaesthesia had been induced is described. At the pre-anaesthetic visit, the 47 year-old female patient had painless restricted mouth opening (two fingers' breadth), dental malpositions, and slight lateral mandibular deviation. Cervical spine movements were normal. She was ranked 3 on the Mallampati scale. The anaesthetic technique preserved spontaneous breathing (induction with propofol 1.5 mg.kg-1 and alfentanil 15 micrograms.kg-1). Manual ventilation was impossible. An oral cannula could not be inserted. As intubation by the normal route was impossible, the retromolar approach had to be used. Several attempts were required for successful intubation by this route. At the end of surgery, the patient was extubated without any difficulties. Postoperative investigations revealed hypertrophic coronoid processes. In this condition, the mandible is jammed by hitting the maxilla, especially when mandibular lifting manoeuvres are used to facilitate manual ventilation and tracheal intubation. Clinical and paraclinical predictors of difficult tracheal intubation seem to be unreliable in such dynamic abnormalities of mouth opening. PMID- 1854058 TI - [Anesthesia for thalamic stimulations: value of flumazenil]. AB - Five cases are reported of peroperative awakening in order to obtain patient cooperation during stereotaxic procedures. General anaesthesia was induced with 0.25 mg.kg-1 midazolam, 1.5 to 2 micrograms.kg-1 fentanyl, and 0.1 mg.kg-1 vecuronium. Maintenance was obtained with isoflurane, nitrous oxide, and small doses of fentanyl. Isoflurane inhalation was discontinued 30 to 40 min before the time of awakening required by surgery. Once expiratory isoflurane concentration reached a level less than or equal to 0.1%, nitrous oxide administration was stopped, and 0.5 mg flumazenil administered. After surgical checking, on the fully awake patient of the efficiency of thalamic stimulation and the lack of any motor deficit, anaesthesia was deepened again, with either isoflurane or a non benzodiazepine intravenous agent. All five patients recovered rapidly and calmly. PMID- 1854059 TI - [Subacute arsenic poisoning]. AB - A cas is reported of a 23-year-old man who voluntarily took a massive dose of arsenic (at least 8 g). In spite of the ingested amount and the acute nature of the poisoning, the patient survived 8 days. Gastrointestinal, neurologic and cardiac features were predominant including nausea, vomiting, choleroid diarrhoea, encephalopathy, peripheral neuropathy, and finally a fatal toxic cardiomyopathy. Metabolic acidosis, moderate cytolysis and an anticoagulant effect were also observed. This unique characteristic was partly due to a circulating anticoagulant with prothrombinase activity, as well as direct antivitamin K activity. Postmortem examination revealed: a congestive oesophagitis; a necrosing gastritis involving all the stomach wall; diffuse hepatic steatosis; skin lesions with vascular congestion and dermoepidermal detachment; discrete subepicardial congestive lesions. Arsenic was found in all tissues. PMID- 1854060 TI - [Intratracheal intubation using a fiberoptic laryngoscope]. AB - Experience with a new type of laryngoscope (Bullard) is reported. It weighs 1,200 kg, and has fiberoptic fibers both for lighting and viewing. Angle of vision is about 55 degrees. Endotracheal intubation with this device requires a semi-rigid stylet to bend the tracheal tube at 90 degrees just above its cuff, so as to reproduce the curvature of the laryngoscope blade. Intubation is carried out in five steps: 1) introducing the laryngoscope blade, and visualising the vocal cords through its lens; 2) introducing the tube with its stylet, just above the laryngoscope blade; 3) placing the tube between the vocal cords under fiberoptic vision; 4) adjusting tube position in the trachea, the stylet still in place; 5) removing both stylet and laryngoscope. The use of this apparatus in an obese patient with reduced mobility of the cervical spine, who was ranked 4 on the Mallampati scale, is reported. The Bullard laryngoscope enabled easy tracheal intubation (duration 1 min 30 s), whereas direct laryngoscopy and the use of a Huffman prism were unsuccessful. The fiberoptic laryngoscope may be of help in case of difficult intubation. PMID- 1854061 TI - [Comment on the checking of nasogastric tubes by epigastric auscultation]. PMID- 1854062 TI - [Sublingual hematoma after difficult intubation]. PMID- 1854063 TI - [Consensus conference in intensive care and emergency medicine. 7th conference: management of non tumoral intracranial hypertension caused by brain edema during intensive care. Paris, December 14 1990]. PMID- 1854064 TI - Evaluation of liver function tests in screening for intra-abdominal injuries. AB - STUDY OBJECTIVES: To determine the utility of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in predicting intra-abdominal injury in blunt trauma patients. DESIGN: Descriptive review of 309 blunt trauma admissions during study period. SETTING: A 1,000-bed Level I trauma center in a major metropolitan area. TYPE OF PARTICIPANTS: Consecutive adult blunt trauma admissions to the trauma service. INTERVENTIONS: Serum levels of study enzymes were measured at initial evaluation and subsequent hospitalization. Results of all intra-abdominal evaluations were recorded. MAIN RESULTS: Significantly greater numbers of patients with SGOT and/or SGPT elevated to more than 130 IU/L had associated intra-abdominal injuries as compared with patients with enzyme elevations of less than 130 IU/L (52% versus 8%). All 18 patients with liver injuries had one or both enzymes elevated to more than 130 IU/L. Higher enzyme levels were more frequently associated with liver injury. CONCLUSIONS: Elevation of serum levels of the study enzymes is a marker for intra abdominal injury. Levels in excess of 130 IU/L are relative indicators of abdominal computed tomography scan. Levels of less than 130 IU/L are unlikely to be associated with liver injury. PMID- 1854065 TI - Base deficit as an indicator of significant abdominal injury. AB - OBJECTIVE: To determine the relative predictive value of the arterial base deficit (BD) as an indicator of intra-abdominal injury (AI) and to compare BD with other indicators (chest injuries, pelvic fractures) of AI. DESIGN: Retrospective case-control analysis. SETTING: University of California San Diego Medical Center. MEASUREMENTS AND MAIN RESULTS: Between January 1985 and July 1988, 3,223 blunt trauma patients were admitted, with complete records available on 3,011. Using a "best fit" multiple logistic regression, BD less than or equal to -6 was the single most important indicator of AI (P less than or equal to .0001), and the odds ratio for AI increased with each category of increasing severity of BD. Admission hypotension, major chest injury, pelvic fracture, and field hypotension (in odds ratio order) also were significantly associated with AI. CONCLUSION: BD is a powerful indicator of AI. A normal BD does not exclude AI, but the presence of a BD less than or equal to -6 in a blunt trauma patient should be considered a strong indication for objective evaluation of the abdomen (ie, diagnostic peritoneal lavage). PMID- 1854066 TI - Blunt traumatic bladder rupture: the role of retrograde cystogram. AB - STUDY OBJECTIVE: We evaluated the importance of microscopic and gross hematuria and the role of retrograde cystography and computed tomography (CT) in the diagnosis of blunt traumatic bladder rupture. DESIGN: All cases at a Level I trauma center between January 1, 1986, and March 31, 1989, were reviewed retrospectively. SETTING: Level I trauma center, university hospital. TYPE OF PARTICIPANTS: All patients with acute blunt abdominal trauma admitted to this Level I trauma center. INTERVENTIONS: The patients' charts were reviewed with emphasis on mode of diagnosis, treatment, and outcome. MEASUREMENTS AND MAIN RESULTS: Twenty-one patients had bladder rupture. All 21 had hematuria with more than 50 RBCs/high-power field, 17 gross and four microscopic. Twenty patients underwent retrograde cystography, which accurately identified bladder rupture, and one was found at laparotomy for other injuries. Seven patients had CT of the abdomen and pelvis, which failed to demonstrate bladder rupture. There were no associated urethral injuries in any of the patients with bladder rupture. CONCLUSION: Significant (more than 50 RBCs/high-power field) hematuria is the principal indication for evaluation for blunt bladder injury, and retrograde cystography is the diagnostic procedure of choice. CT is neither sensitive nor specific enough as primary diagnostic modality. PMID- 1854067 TI - Injuries from tire and wheel explosions during servicing. AB - STUDY OBJECTIVE: To evaluate injuries from tire and wheel explosions that occur during servicing. DESIGN: Retrospective analysis of all injury reports from the National Highway Traffic Safety Administration, the Occupational Safety and Health Administration, and the Insurance Institute for Highway Safety. RESULTS: For the period of 1978 through 1987, there were 694 reported injuries from explosions during tire servicing; 143 of them were fatal, resulting mainly from truck tires. Because the three data sources used different methods for case finding and covered different time periods, the actual number of such injuries was probably greater. Head injuries accounted for 78% of the deaths and 24% of nonfatal injuries. The proportion of injuries occurring during tire inflation declined from 51% in 1978 to 33% in 1987 (P less than .05). Fatal injuries involving single-piece rim wheels increased during the 1980s as multipiece rim wheels were phased out by the trucking industry. CONCLUSIONS: Exploding truck tires and wheel rims cause serious injuries. The use of safety cages during inflation as required by a 1980 Occupational Safety and Health Administration standard appears to have reduced injuries during truck tire inflation. The use of helmets during servicing may further reduce serious injuries. PMID- 1854068 TI - A prospective study of the impact of helmet usage on motorcycle trauma. AB - STUDY OBJECTIVE: To determine the effect of the use of a motorcycle helmet on reducing the mortality, morbidity, and health care costs resulting from motorcycle crashes. DESIGN: A prospective, multicenter study of all eligible motorcycle crash victims. SETTING: The emergency departments of eight medical centers across the state of Illinois, including representatives from urban, rural, teaching, and community facilities. TYPE OF PARTICIPANTS: All motorcycle crash victims presenting less than 24 hours after injury for whom helmet information was known. Data were collected from April 1 through October 31, 1988. MEASUREMENTS AND MAIN RESULTS: Fifty-eight of 398 patients (14.6%) were helmeted, and 340 (85.4%) were not. The nonhelmeted patients had higher Injury Severity Scores (11.9 vs 7.02), sustained head/neck injuries more frequently (41.7 vs 24.1%), and had lower Glasgow Coma Scores (13.73 vs 14.51). Twenty-five of the 26 fatalities were nonhelmeted patients. By logistic regression, the lack of helmet use was found to be a major risk factor for increased severity of injury. A 23% increase in health care costs was demonstrated for nonhelmeted patients (average charges $7,208 vs $5,852). CONCLUSION: Helmet use may reduce the overall severity of injury and the incidence of head injuries resulting from motorcycle crashes. A trend toward higher health care costs was demonstrated in the nonhelmeted patients. PMID- 1854069 TI - Study design in prehospital trauma advanced life support-basic life support research: a critical review. AB - The best method of prehospital care for the trauma victim remains controversial. Nine studies that compare advanced life support to basic life support for prehospital trauma care are reviewed. Limitations in the study designs are noted, and suggestions are made for more uniform reporting in prehospital trauma research. PMID- 1854070 TI - Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the Utstein Style. Task Force of the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, and the Australian Resuscitation Council. PMID- 1854071 TI - Forces acting during air and ground transport on patients stabilized by standard immobilization techniques. AB - OBJECTIVE: Transportation, whether by air or ground, exposes the injured patient to mechanical shocks and vibrations. These forces and their hazardous potential remain largely unknown. The purpose of this study was to identify, characterize, and compare the forces generated during patient transport in helicopter and ground ambulances. METHODS: Forces generated during transport were measured using an instrumented, low mass triaxial accelerometer fixed to a standard backboard. Measurements were recorded in three axes with an adult subject immobilized on the board during experimental ambulance and helicopter trials. Acceleration waveforms were analyzed in each mode of transport. RESULTS: Forces for both ground and air transport ranged 0.07g to 0.19g root mean square, and 0.32g to 0.83g mean peak. The vibrational forces in the helicopter were fairly discrete, located at 6.6, 19.5, and 39 Hz, and axis dependent. Ground ambulance vibrations were more diffuse, occurring below 1 Hz and between 10 and 15 Hz. Crest factor analysis shows that shocks were more uniform in the helicopter than on the ground, especially in the anterior-posterior axis. CONCLUSION: These data suggest that transportation by helicopter subjects supine patients to greater lateral and vertical forces, but smaller head to toe forces, than ground transportation (P less than .05). In general, the forces to which a backboarded subject is subjected during transport range from 0.32g to 0.83g, vary by direction, and are more predictable for air than for ground transport. The clinical significance of these measurements requires further study. PMID- 1854072 TI - Spinal immobilization on a flat backboard: does it result in neutral position of the cervical spine? AB - STUDY OBJECTIVES: To determine the amount of occipital padding required to achieve neutral position of the cervical spine when a patient is immobilized on a flat backboard. Neutral position was defined as the normal anatomic position of the head and torso that one assumes when standing looking straight ahead. DESIGN: Descriptive with hypothesis testing of selected descriptive elements. SETTING: University campus and hospital. SUBJECTS: One hundred healthy young adults with no history of back disease. INTERVENTIONS: Volunteers were measured in standing and supine positions. MEASUREMENTS: Occipital offset; height; weight; and head, neck, and chest circumferences were measured for each subject. MAIN RESULTS: The amount of occipital offset required to achieve neutral position varied from 0 to 3.75 in. (mean, 1.5 in.). Mean occipital offset for men (1.67 in.) was significantly greater than that for women (1.31 in.) Easily obtained body measurements did not accurately predict occipital offset. CONCLUSION: Immobilization on a flat backboard would place 98% of our study subjects in relative cervical extension. Occipital padding would place a greater percentage of patients in neutral position and increase patient comfort during transport. PMID- 1854073 TI - Outcome of patients with blunt trauma transferred after diagnostic or treatment procedures or four-hour delay. AB - STUDY OBJECTIVE: This study was conducted to assess the outcome of patients suffering multiple injuries from blunt trauma who were transferred to a Level I trauma center for definitive care after special diagnostic or treatment procedures (DTPs) or after a simple delay of four hours at a primary receiving hospital. DESIGN: Retrospective review of aeromedical registry data and clinical chart review. MEASUREMENTS: Aeromedical trauma transfers made during a four-year period were studied. The TRISS method was used to determine predicted survivals for DTP patients, patients transferred after a four-hour delay, and patients transferred promptly. RESULTS: The observed survival for 469 aeromedically transferred patients with blunt trauma was the same as that predicted by TRISS analysis (394 vs 392.5). Survival for 86 patients with DTP was also the same as predicted (62 vs 61.6). Outcomes for nonDTP patients and for 92 patients experiencing a delay in transport of four hours or more were also the same as predicted. CONCLUSION: Early versus delayed decision to transfer patients with blunt trauma did not appear to influence overall outcome. These data suggest that minor delays in recognizing the need to transfer patients with blunt injuries to a trauma center for definitive care may be offset by rapid, skilled transfer and highly specialized trauma care and support the hypothesis that regional trauma center care after initial evaluation and resuscitation elsewhere can be effective even when the timing of transfer is not ideal. PMID- 1854074 TI - An evaluation of pulse oximetry in prehospital care. AB - STUDY OBJECTIVES: We performed this study to evaluate the accuracy of pulse oximetry oxygen saturation (SpO2) against direct measurements of arterial oxygen saturation (SaO2) in the field. DESIGN: Prospective, cross-sectional, paired measurements of SpO2 against SaO2. SETTING: This evaluation was done in the prehospital setting. INTERVENTIONS: A pulse oximeter with digital probe was used to measure SpO2 in 30 patients. Arterial blood gases were drawn in the field while the pulse oximeter was in use, and oxygen saturation (HbO2) was measured by CO-oximetry. MAIN RESULTS: There was no significant difference between SpO2 (94.6 +/- 5.4%) and HbO2 (94.9 +/- 5.1%) (P = .495, beta less than .2). There was a strong correlation between SpO2 and HbO2 (r = .898). The bias between SpO2 and HbO2 was -0.3, with a precision of 2.4. When SpO2 was 88% or more, HbO2 was 90% or more in every case. Mean carboxyhemoglobin was 1.3 +/- 0.9%, and mean methemoglobin was 0.9 +/- 0.3%. There was no significant difference between the pulse oximeter heart rate and the ECG heart rate (P = .223, beta less than .2). CONCLUSION: We conclude that pulse oximetry is sufficiently accurate to be useful in the field when SpO2 is more than 88%. It is potentially useful in patients with clinical signs of acute hypoxemia and in patients receiving interventions that may produce acute hypoxemia. Further work is needed to evaluate the accuracy of pulse oximetry in the settings of elevated carboxyhemoglobin, methemoglobin, and very low saturations. PMID- 1854075 TI - Efficacy and safety of prehospital rewarming techniques to treat accidental hypothermia. AB - STUDY OBJECTIVE: Evaluation of inhalation rewarming and peripheral rewarming for reducing the body core temperature afterdrop and accelerating rewarming rates. DESIGN: Prospective, randomized human experimentation. SETTING: Physiology laboratory with cooling during ice water immersion and rewarming in rescue sleeping bags in a windy, cold (2 C) air environment. TYPE OF PARTICIPANTS: Eight experimental subjects who were cooled to clinical hypothermia (35.0 C), rectal or esophageal temperature (Tr or Te). MEASUREMENTS AND MAIN RESULTS: Afterdrop was characterized as minimum Tr and Te plus recovery time to the Tr and Te levels at the onset of rewarming. Rewarming rates 30 and 60 minutes after maximum afterdrop for Tr and Te were measured. By analysis of variance, inhalation rewarming and peripheral rewarming evaluated separately or in combination did not significantly influence afterdrop duration, afterdrop recovery, or rewarming rates. CONCLUSION: With no physiological benefit and hazards identified (inhalation rewarming burning the face, peripheral rewarming eliminating carbon monoxide equal to 300 to 600 ppm), inhalation rewarming and peripheral rewarming are not recommended for the prehospital treatment of mild hypothermia. PMID- 1854076 TI - Cardiac rupture secondary to blunt trauma: a rapidly diagnosable entity with two dimensional echocardiography. AB - A 58-year-old woman involved in a single automobile accident sustained an isolated rupture of the right ventricle without any other obvious form of external trauma. On presentation to an outlying hospital, hypotension was the only apparent clinical finding suggestive of injury. After several hours of delay, the patient was transferred to a tertiary medical center. The diagnosis of cardiac rupture was made by two-dimensional echocardiography. The patient underwent successful surgical repair and was discharged home in good condition eight days after sustaining this potentially fatal injury. PMID- 1854077 TI - Blunt trauma-induced pacemaker failure. AB - A 54-year-old man with an artificial pacemaker sustained blunt trauma to his chest when he was struck with a baseball bat. Within 15 minutes after the injury, the patient experienced cardiovascular collapse. His pacemaker failed, and he required insertion of a temporary transvenous pacemaker. At surgery, the defect was traced to failure of the pulse generator, a rare cause of pacemaker failure. Emergency department evaluation should include prompt and continuous ECG monitoring, an overpenetrated chest radiograph, and telemetry evaluation after discharge. PMID- 1854078 TI - Successful epicardial pacing in blunt trauma resuscitation. AB - Epicardial pacing wires were used successfully in the resuscitation of a moribund victim of blunt trauma after fluid resuscitation and chemical measures had failed. Application of these wires to treat the bradycardia of shock should be considered in selected patients when standard measures fail. PMID- 1854079 TI - Ruptured interstitial pregnancy presenting as an intrauterine pregnancy by ultrasound. AB - Interstitial pregnancy is an uncommon subset of ectopic pregnancy in which the conceptum implants in the intrauterine portion of the fallopian tube. These pregnancies tend to progress further before rupture than do other tubal pregnancies and subsequently have greater propensity for massive intra-abdominal bleeding and maternal demise. Abdominal ultrasound can be deceptive in evaluating interstitial ectopic pregnancies. Transvaginal ultrasonography is more sensitive in the diagnosis of early ectopic pregnancy. Knowledge of the application and limitations of both transabdominal and transvaginal ultrasound will assist the emergency physician in the timely evaluation of this potentially lethal condition. PMID- 1854080 TI - Continuous intravenous infusion fentanyl for sedation and analgesia of the multiple trauma patient. AB - Fentanyl is an attractive agent for analgesia in the emergency department. Its use in this setting has been limited to IV bolus administration. We report successful sedation, muscle relaxation, and analgesia of a multiple trauma patient with fentanyl IV bolus and continuous infusion in the ED. PMID- 1854081 TI - A pseudoaneurysm of the superficial femoral artery as a late complication of a stab wound. AB - Limited arteriography based on clinical indications has become increasingly popular. We present the case of a patient with pseudoaneurysm formation of the superficial femoral artery as a late consequence of a lateral stab wound to the thigh. This case demonstrates the need for postinjury follow-up to identify missed injuries before they are limb threatening. PMID- 1854082 TI - The Utstein Abbey and survival from cardiac arrest: what is the connection? PMID- 1854083 TI - Core Content for Emergency Medicine. American College of Emergency Physicians. American Board of Emergency Medicine. Society for Academic Emergency Medicine. PMID- 1854084 TI - Prehospital 12-lead ECGs. PMID- 1854085 TI - 'Economic malpractice': inappropriate use of cost analysis. PMID- 1854086 TI - Lost dog tag chain. PMID- 1854087 TI - Cardiovascular effects of xylazine and detomidine in horses. AB - The cardiovascular effects of xylazine and detomidine in horses were studied. Six horses were given each of the following 5 treatments, at 1-week intervals: xylazine, 1.1 mg/kg, IV; xylazine, 2.2 mg/kg, IM; detomidine, 0.01 mg/kg, IV; detomidine, 0.02 mg/kg, IV; and detomidine, 0.04 mg/kg, IM. All treatments resulted in significantly decreased heart rate, increased incidence of atrioventricular block, and decreased cardiac output and cardiac index; cardiac output and cardiac index were lowest following IV administration of 0.02 mg of detomidine/kg. Mean arterial pressure was significantly reduced for various periods with all treatments; however, IV administration of 0.02 mg of detomidine/kg caused hypertension initially. Systemic vascular resistance was increased by all treatments. Indices of ventricular contractility and relaxation, +dP/dt and -dP/dt, were significantly depressed by all treatments. Significant changes were not detected in stroke volume or ejection fraction. The PCV was significantly reduced by all treatments. Respiratory rate was significantly decreased with all treatments, but arterial carbon dioxide tension did not change. Arterial oxygen tension was significantly decreased briefly with the 3 IV treatments only. PMID- 1854088 TI - Comparison of effects of cimetidine and omeprazole on mechanically created gastric ulceration and on aspirin-induced gastritis in dogs. AB - A double-blind study was conducted to compare gastric ulcer healing time in nontreated dogs with that in dogs treated with either cimetidine or omeprazole. Single ulcers were created in the gastric antrum by use of a suction biopsy capsule. Each dog was given 25 mg of aspirin/kg of body weight orally for 20 days after ulcer induction. Five control dogs were given aspirin only (no anti-ulcer medication) during the 20-day study. Six dogs were given cimetidine at dosage of 10 mg/kg orally every 8 hours, and 6 dogs were given omeprazole orally at dosage of 2 mumol/kg (0.7 mg/kg) once daily. All dogs were examined endoscopically on days 5, 10, 15, and 20 and were given a score for the size of the mechanically created ulcer and a score for the degree of aspirin-induced gastritis. All dogs were euthanatized on day 21, and gastric lesions were examined histologically. Significant differences were not evident in ulcer healing scores or degree of aspirin-induced gastritis among treated and nontreated dogs on days 5, 10, 15, and 20. However, aspirin-induced gastritis was less severe in dogs of the omeprazole group than in dogs of the cimetidine or control group on each day observations were made. The effect of omeprazole given once daily was comparable with that of cimetidine given every 8 hours in lessening aspirin-induced gastritis. PMID- 1854089 TI - Effect of midazolam preanesthetic administration on thiamylal induction requirement in dogs. AB - The thiamylal sparing effect of midazolam was studied in 30 healthy Beagle and mixed-breed dogs. Using a replicated Latin square design, all dogs were given placebo (saline solution) and 0.025, 0.05, 0.1, and 0.2 mg of midazolam/kg of body weight prior to IV administration of thiamylal sodium. The 0.1 and 0.2 mg/kg dosages significantly decreased the amount of thiamylal required to obtund swallowing reflex and easily achieve endotracheal intubation. Midazolam at 0.1 and 0.2 mg/kg reduced thiamylal requirement by 16.4% and 18.9%, respectively, whereas the 0.05 mg/kg dosage decreased thiamylal requirement by only 6.8%. The 0.2 mg/kg dosage did not further decrease thiamylal requirement beyond that achieved with the 0.1 mg/kg dosage of midazolam. This study demonstrates that the preanesthetic IV administration of midazolam reduces the thiamylal dose necessary to accomplish intubation. The optimal preanesthetic dosage (lowest dosage with significant effect) was 0.1 mg/kg. PMID- 1854090 TI - Comparison of several combinations for anesthesia in rabbits. AB - Few safe and effective anesthesia regimens have been described for use in rabbits, partially because of the susceptibility of this species to sometimes fatal respiratory depression. Although inhalant anesthetics are generally safer than injectable anesthetics, their use may be limited by lack of equipment or facilities. This study was conducted to compare effects of several injectable anesthetics in rabbits on response to noxious stimuli, heart rate, respiratory rate, and rectal temperature. Six injectable anesthetic combinations were administered to rabbits: xylazine-ethyl-(1-methyl-propyl) malonyl-thio-urea salt (EMTU), ketamine-EMTU, xylazine-pentobarbital, xylazine-acepromazine-ketamine (XAK), ketamine-chloral hydrate, and ketamine-xylazine. All combinations induced a depression of respiratory rate. Although rectal temperature values were reduced to some degree in each group, the most profound hypothermia was induced by XAK. The combination that induced the longest duration of anesthesia was XAK. It was concluded that XAK was preferable for longer periods of anesthesia (60 to 120 minutes), although it induces severe hypothermia. For short periods of anesthesia, xylazine-pentobarbital, xylazine-EMTU, or ketamine-xylazine were deemed adequate; however, xylazine-EMTU induced the best survivability and consistency. PMID- 1854091 TI - Effect of administration of phenylbutazone or progesterone on recovery of embryos from the uterus of mares 5 days after ovulation. AB - Twelve horse mares were used to investigate the effect of phenylbutazone or progesterone administration on uterine tubal motility, as reflected by embryo recovery from the uterus on day 5 after ovulation. Four treatment groups were used: group A (controls), in which uterine flush was performed 7 to 11 days after ovulation; group B (5-day controls), in which uterine flush was performed 5 days after ovulation; group C, in which uterine flush was performed 5 days after ovulation following administration of phenylbutazone (2 g, IV) on day 3; and group D, in which uterine flush was performed 5 days after ovulation following administration of progesterone in oil (250 mg, IM) on days 0, 1, and 2. Each mare was randomly assigned to each group once. Embryo recovery for each group was: group A, 13 embryos from 12 mares; group B, 3 embryos from 12 mares; group C, 4 embryos from 11 mares; and group D, 1 embryo from 11 mares. Recovery of embryos on day 5 in 3 of 12 nontreated mares indicated that equine embryos may enter the uterus before day 6. Neither treatment increased embryo recovery from the uterus on day 5 over that from the uterus of the 5-day controls. PMID- 1854092 TI - Retrograde flow of spermatozoa into the urinary bladder of cats during electroejaculation, collection of semen with an artificial vagina, and mating. AB - The effect of methoxamine on retrograde flow of spermatozoa into the urinary bladder of domestic cats during electroejaculation and the incidence of retrograde flow during the collection of semen with an artificial vagina, or during mating was examined. In experiment 1, urine collected by cystocentesis prior to electroejaculation was azoospermic or contained few, nonmotile spermatozoa, whereas urine collected after electroejaculation contained more (P = 0.002) spermatozoa, and motile spermatozoa were evident in urine obtained from 6 of 8 cats. Administration of methoxamine hydrochloride (200 micrograms/kg of body weight, IV) did not affect spermatozoal output or percentage of retrograde flow. Percentage of retrograde flow for control cats ranged from 61.18 to 92.95% (mean +/- SD, 80.00 +/- 14.28%) and for methoxamine-treated cats, ranged from 15.25 to 92.49% (mean +/- SD, 58.10 +/- 32.28%), but the difference was not significant. In experiment 2, an artificial vagina was used to collect semen from 5 of the 8 cats used in experiment 1. Urine collected by cystocentesis after ejaculation contained spermatozoa, and motile spermatozoa were evident in the urine from 4 of 5 cats. The mean (+/- SD) percentage of retrograde flow for these 5 cats was 46.82 +/- 31.67% (range, 14.56 to 90.32%). In experiment 3, each of the 5 cats that were used in experiments 1 and 2 were mated. Spermatozoa were recovered from the vagina of each mated female, and motile spermatozoa were also present in postejaculation urine obtained by cystocentesis from each of the 5 male cats. Mean total number of spermatozoa in the postmating urine was 29.42 +/- 33.58 x 10(6) (range, 0.22 x 10(6) to 76.05 x 10(6) spermatozoa).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854093 TI - Evaluation of intravenous administration of concentrated immunoglobulin G to colostrum-deprived foals. AB - Ten foals of various breeds were deprived of colostrum from birth to 36 hours of age, then were allotted to 2 groups. Foals of group 1 (n = 6) were given 20 g (200 ml) of purified equine IgG IV in a 10% solution, and foals of group 2 (n = 4) were given 30 g (300 ml) of the same preparation. Total administration time for each 10 g of IgG in 100 ml was approximately 10 minutes. Serum IgG concentration in foals was assessed prior to, between 24 and 48 hours, and at 7 and 14 days after IgG administration. Between 24 and 48 hours after IgG administration, mean serum IgG concentration in group-1 foals was 425 mg/dl (range, 350 to 480 mg/dl). Mean body weight for this group of foals was 50.3 kg (range, 43.3 to 54.7 kg). For group-2 foals, mean serum IgG concentration was 768 mg/dl (range, 640 to 920 mg/dl) between 24 and 48 hours after administration of IgG. Foals of this group had mean body weight of 43.2 kg (range, 36.5 to 47.5 kg). Serum IgG concentration in group-2 foals at 24 to 48 hours was significantly (P = 0.005) greater than that in group-1 foals. Mean total IgG recovery at 24 to 48 hours, calculated on the basis of 94.5 ml of plasma volume/kg of body weight, was approximately 100%. Values of IgG measured in all foals 1 and 2 weeks after administration of the IgG concentrate were equivalent to values expected after normal decay of passively acquired IgG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854094 TI - Isolation of a major form of pepsinogen from gastric mucosa of horses. AB - In mammalian species studied previously, pepsinogen consisted of biochemically different groups of isozymogens. By use of gel filtration chromatography and electrophoresis, we isolated a predominant pepsinogen from the gastric mucosa of a horse. Peptide mapping with V8 protease revealed differences with its porcine homologue. However, porcine and equine pepsinogens, when activated to pepsin, had a similar pattern of activity when hemoglobin was used as substrate. Those results suggest that differences must exist in the primary structure of the pepsinogens of the 2 species. PMID- 1854095 TI - Comparison of fractional excretion and 24-hour urinary excretion of sodium and potassium in clinically normal cats and cats with induced chronic renal failure. AB - The influence of induced chronic renal failure on 24-hour urinary excretion and fractional excretion of sodium and potassium was studied in cats. Induction of chronic renal failure significantly increased fractional excretion of potassium (P less than 0.0001) and sodium (P less than 0.05); however, 24-hour urinary excretion of sodium and potassium decreased slightly following induction of chronic renal failure. Fractional excretion and 24-hour urinary excretion of sodium and potassium were compared by linear regression in clinically normal cats, cats with chronic renal failure, and clinically normal and affected cats combined. In clinically normal cats, linear regression revealed only moderate correlation between fractional excretion and 24-hour urinary excretion for sodium and potassium. Linear regression of these same relationships in cats with chronic renal failure, and in clinically normal cats and cats with chronic renal failure combined, indicated low correlation. Fractional excretions of sodium and potassium were not reliable indicators of 24-hour urinary excretion of these electrolytes in cats with chronic renal failure or unknown glomerular filtration rate. Fractional excretion of potassium and sodium correlated only moderately with 24-hour urinary excretion in clinically normal cats. PMID- 1854096 TI - Evaluation of flow cytometric counting procedure for canine reticulocytes by use of thiazole orange. AB - An automated reticulocyte counting method that used a flow cytometer and the nucleic acid staining dye, thiazole orange, was developed. Anticoagulated (EDTA) blood specimens were suitable for flow cytometric reticulocyte counting when stored at 4 C for 96 hours after collection. Thiazole orange-stained samples were stable for 5.5 hours after staining when stored capped at 20 C and protected from light. Flow cytometric and manual microscopic reticulocyte counts were compared for counts in the 0.27 to 5.32% range (as determined by flow cytometry) and 0.10 to 4.90% range (as determined by 1 technician). Although the results of flow cytometric analysis generally correlated well (r = 0.821) with manual counts, there was poor correlation between the procedures for counts less than or equal to 2.0% (r less than or equal to 0.272). Linearity of flow cytometric counts over the range 0.27 to 14.46% was excellent (r = 0.999). Within-run precision of flow cytometric counts (% coefficient of variation [cv] = 3 to 5) was superior to manual microscopic counts obtained by one technician (% cv = 19 to 23) and to manual microscopic counts, which were an average of counts done by 3 technicians (% cv = 8 to 18). Comparable flow cytometric counts were obtained by counting 50,000 or 100,000 blood cells in the flow cytometer. PMID- 1854097 TI - Effect of repeated phlebotomy on iron status of rhesus monkeys (Macaca mulatta). AB - Iron status, as determined by hematologic values, serum iron concentration, total iron-binding capacity, and zinc protoporphyrin concentration, was determined in 2 groups of 6 nonpregnant monkeys. Monkeys of groups 1 and 2 had 10 and 5%, respectively, of their blood volume withdrawn per week for up to 10 weeks or until blood hemoglobin concentration was less than or equal to 10 g/dl. A third group of 6 monkeys served as controls. The majority (8/12) of the monkeys became anemic (hemoglobin concentration, less than or equal to 10 g/dl) after approximately 30 to 70% (mean, 49%) of their blood volume was removed. Anemia was accompanied by decrease in serum iron concentration and percentage of transferrin saturation. Microcytosis, hypochromasia, and increased zinc protoporphyrin concentration, all hematologic characteristics of iron deficiency, developed later. The calculated iron stores ranged from 1 to 133 mg, with mean value of 51 mg. Iron-depleted monkeys had mean calculated available iron store of 20.8 mg, whereas iron-replete monkeys had mean available iron store of 114.0 mg. Changes were not observed in monkeys of the control group during the study period. None of the baseline hematologic or biochemical analytes measured were good predictors of iron stores. The diet used at the research center did not provide sufficient iron to prevent iron deficiency in most of the monkeys from which a total amount of 30 to 70% of blood volume at 5 or 10%/week was withdrawn. Studies requiring that much blood may need to be modified to include iron supplementation, reduction of sample volume, or iron replacement after termination of projects. PMID- 1854098 TI - Intestinal responses to enterotoxigenic Escherichia coli heat-stable toxin b in non-porcine species. AB - The Escherichia coli heat-stable enterotoxin (STb) is the most prevalent toxin associated with diarrheagenic E coli isolates of porcine origin. Unequivocal biological activity of this toxin has been observed only in swine intestine. In this study, when endogenous protease activity was blocked with soybean trypsin inhibitor, intestinal secretion was stimulated by STb in jejunal loops of rats, mice, calves, and rabbits. Compared with pigs, rats, mice, and calves, rabbits were relatively insensitive to STb. These data demonstrate that the activity of STb is not a species-specific toxic activity; there is species variation in sensitivity to STb, and some common laboratory animals may have potential to be used to measure biological activity of STb. PMID- 1854099 TI - Identity of Bacteroides isolates and previously named Bacteroides spp in clinical specimens of animal origin. AB - During the years 1984 through 1987 2,574 isolates of obligately anaerobic bacteria were isolated from samples submitted for analysis. The most common anaerobic isolates were members of the genus Bacteroides, representing 44.6% of the isolates. Of these, the most commonly isolated identifiable microorganisms were bile-resistant and nonpigmented, belonging to the B fragilis group of Bacteroides. Importantly, obvious predilections for any one species or group of Bacteroides were not apparent for animal or site (condition), except that the proportion of isolates belonging to the nonpigmented, bile-resistant group obtained from the respiratory tract was significantly (P less than 0.005) higher than that not belonging to this group. On the other hand, the proportion of isolates of the non-pigmented, bile-resistant group obtained from abscesses was significantly lower than that not belonging to this group. PMID- 1854100 TI - Acute hemolytic anemia after oral administration of L-tryptophan in ponies. AB - The hematologic and pathologic effects of orally administered L-tryptophan and indoleactic acid and of L-tryptophan administered IV were studied in ponies. Sixteen adult Shetland ponies were allotted into 4 experimental groups. Group 1 consisted of 5 ponies (1-5) given 0.6 g of tryptophan/kg of body weight in a water slurry via stomach tube. Group 2 included 4 ponies (6-9) given 0.35 g of tryptophan/kg orally. Group-3 ponies (10-13) were given 0.35 g of indoleacetic acid/kg orally. Group 4 consisted of 3 ponies (14-16) given a single 4-hour IV infusion of 0.1 g of tryptophan/kg. Restlessness, increased respiratory rate, hemolysis, and hemoglobinuria were detected in 4 of the 5 group-1 ponies. Only pony 7 in group 2 developed hemolysis, hemoglobinuria, and a significant increase in respiratory rate. Renal pathologic lesions, consistent with hemoglobinuric nephrosis, were seen in ponies 2, 4, 5, and 7. Bronchiolar degeneration was evident in 4 of 9 ponies given tryptophan orally. The importance of these respiratory lesions was unknown. Clinical or pathologic abnormalities were not noticed in the ponies of groups 3 and 4. Mean plasma tryptophan values increased significantly in groups 1 and 2 at 6 hours after dosing. A second peak of tryptophan was detected in both groups at 12 hours. Values returned to predose values by 48 hours. Plasma indole and 3-methylindole concentrations were detectable in only 2 ponies (4 and 7). In vitro incubations of cecal fluid from ponies 6, 8, and 9 yielded a percentage conversion of tryptophan to indole of 16.75%, 5.84%, and 7.96%, respectively. 3-Methylindole was not produced. These results suggested that indole was the major metabolite of orally administered tryptophan in these ponies. PMID- 1854101 TI - Acute hemolytic anemia induced by oral administration of indole in ponies. AB - Eight ponies were allotted to 2 groups of 4. Group-1 ponies (1-4) were given 0.2 g of indole/kg of body weight orally and group-2 ponies (5 to 8) were given 0.1 g of indole/kg. Various physical, hematologic, and physiologic measurements were obtained after administration of indole. Intravascular hemolysis and hemoglobinuria were detected in both groups within 24 hours of dosing. Hemolysis was reflected by decreases in PCV, hemoglobin concentration, and RBC count, and an increase in indirect bilirubin. Erythrocyte fragility appeared to increase in both groups at 8 hours after dosing and peaked at 16 hours after dosing. At 72 hours after dosing, the RBC fragility value was less than predose measurements. Heinz body formation was noticed in group-2 ponies, but not in group 1. Plasma indole concentrations increased in both groups from the nondetectable predose concentrations. Group-1 values were 203% of group-2 values. In group 2, plasma indole was nondetectable by 12 hours, whereas low concentrations could still be measured in the group-1 ponies at 24 hours. Ponies in group 1 died or were euthanatized between 24 and 72 hours after dosing, whereas group-2 ponies were euthanatized between 48 and 120 hours. At necropsy, all body fat, mucous membranes, and elastic tissue were stained yellow. Hemoglobinuric nephrosis was the most prominent microscopic lesion. Results of this study indicated that indole, a metabolite of the amino acid tryptophan, causes acute intravascular hemolysis in ponies. PMID- 1854102 TI - Immunity in swine inoculated with larvae or extracts of a pig isolate and a sylvatic isolate of Trichinella spiralis. AB - Inoculation of swine with a sylvatic isolate of Trichinella spiralis, designated T s nativa, resulted in low numbers of muscle larvae, compared with muscle larvae accumulation in swine inoculated with a pig type of T s spiralis. Despite low infectivity of T s nativa for swine, primary inoculation resulted in high levels of immunity against challenge infection with T s spiralis. This immunity was expressed in accelerated expulsion of challenge adults from the intestine and reduced numbers of muscle larvae. Pigs inoculated with T s nativa developed cellular and humoral responses similar to those in pigs inoculated with T s spiralis. However, in immunoblots, sera from pigs inoculated with T s nativa recognized additional proteins in muscle larvae excretory-secretory (ES) products, compared with sera from pigs inoculated with T s spiralis. Active immunization of pigs with ES products from T s nativa resulted in numerically higher, but not significantly different levels of immunity, compared with pigs immunized with ES from T s spiralis. The highest levels of immunity were obtained in pigs immunized with a T s spiralis newborn larval extract. The combination of ES products and newborn larval extract did not result in additive levels of immunity. These results indicate that the major immune effector response to Trichinella sp in pigs is against the newborn larvae, regardless of the genetic type of Trichinella sp. PMID- 1854103 TI - Prospective vaccine prepared from a new mutant of Toxoplasma gondii for use in cats. AB - Kittens are the principal disseminators of Toxoplasma gondii. They can shed greater than 10(8) oocysts in the feces after initial infection with bradyzoites in tissue cysts. Thereafter, most kittens develop protective immunity and do not shed oocysts again if they are reinfected. Bradyzoites of a T gondii mutant, designated T-263, were used to vaccinate kittens. Their use did not result in oocyst shedding, but successfully prevented 84% (31/37) of the kittens from shedding oocysts when challenge exposed with a normal isolate of T gondii. Vaccination of outdoor-roaming cats and kittens would be a useful public health measure to prevent transmission of toxoplasmosis near homes, on farms, and in zoos. It is anticipated that several years will be required for a lyophilized bradyzoite vaccine to be ready for licensing and possible commercial availability. PMID- 1854104 TI - Effects of sodium hyaluronate on tendon healing and adhesion formation in horses. AB - Sodium hyaluronate reduces adhesions after tendon repair in rodents and dogs, and has been used in limited clinical trials in people. To evaluate its effect on tendon healing and adhesion formation in horses and to compare these effects with those of a compound of similar visco-elastic properties, a study was performed in horses, using a model of collagenase injection in the flexor tendons within the digital sheath. Eight clinically normal horses were randomly allotted to 2 groups. Adhesion formation between the deep digital flexor tendon and the tendon sheath at the pastern region was induced in the forelimbs of all horses. Using tenoscopic control, a 20-gauge needle was inserted into the deep digital flexor tendon of horses under general anesthesia and 0.2 ml of collagenase (2.5 mg/ml) was injected. The procedure was repeated proximally at 2 other sites, spaced 1.5 cm apart. A biopsy forceps was introduced, and a 5-mm tendon defect was created at each injection site. Group-A horses had 120 mg of sodium hyaluronate (NaHA) gel injected into the tendon sheath of one limb. Group-B horses had methylcellulose gel injected at the same sites. The contralateral limbs of horses in both groups served as surgical, but noninjected, controls. Horses were euthanatized after 8 weeks of stall rest. Ultrasonographic evaluation revealed improved tendon healing after NaHa injection, but no difference in peritendinous adhesion formation. Tendon sheath fluid volume and hyaluronic acid (HA) content were greater in NaHA-treated limbs. Gross pathologic examination revealed considerably fewer and smaller adhesions when limbs were treated with NaHA. However, significant difference in pull-out strengths was not evident between NaHA-treated and control limbs. Histologically, the deep digital flexor tendon from the NaHA-treated limbs had reduced inflammatory cell infiltration, improved tendon structure, and less intratendinous hemorrhage. Treatment with methylcullulose had no significant effect on tendon healing, adhesion size, quantity, or strength or on the volume and composition of the tendon sheath fluid. Sodium hyaluronate, administered intrathecally, appears to have a pharmaceutically beneficial action in this collagenase-induced tendinitis and adhesion model in horses. PMID- 1854105 TI - Effect of left hepatic vein ligation on hepatic circulation, function, and microanatomy in dogs. AB - Eighteen healthy dogs were allotted to 3 groups (n = 6 dogs each). All dogs were evaluated at the beginning of the study by complete physical examination; total and differential WBC counts; serum biochemical analysis (alanine transaminase and alkaline phosphatase activities and bilirubin and albumin concentrations); sulfobromophthalein excretion, ammonia tolerance, and glucagon response testing; portal and intraparenchymal pressure determinations; operative mesenteric portography; and histologic assessment of hepatic biopsy specimens. The left hepatic vein was ligated completely in dogs of groups 1 and 2. Group-3 (control) dogs had a ligature placed loosely around the left hepatic vein. Dogs of groups 1 and 3 were reevaluated 24 hours after surgery by use of the aforementioned hematologic and biochemical tests. Group-1 dogs were reevaluated by use of portal and intraparenchymal pressure determinations, jejunal vein portography, and complete necropsy at 48 hours after surgery. At 4 weeks after surgery, dogs of groups 2 and 3 were reevaluated by use of all aforementioned tests. Results indicated transient hepatic congestion, which resolved by the fourth postoperative week. Longstanding effect on hepatic structure, circulation, or function was not found. We concluded that left hepatic vein ligation in clinically normal dogs does not cause severe or permanent liver damage. PMID- 1854106 TI - Use of biometry and keratometry for determining optimal power for intraocular lens implants in dogs. AB - Axial length and corneal curvature were determined by use of A-scan ultrasonography and keratometry on both eyes of dogs of various breeds, sizes, and ages. Mean axial length was 20.43 +/- 1.48 mm; axial length was not related to age or sex, but was significantly greater (P = 0.047) in dogs of larger breeds. Mean corneal curvature was 39.94 +/- 2.61 diopters. Dogs of large breeds had significantly (P less than 0.001) flatter corneas. Mild, roughly symmetric astigmatism was detected in a majority of dogs. Use of mean values in a theoretic artificial intraocular lens power equation suggests that aphakic dogs require an implant of approximately 40 diopters to achieve emmetropia. PMID- 1854107 TI - Association between solar radiation and ocular squamous cell carcinoma in cattle. AB - The association between ocular squamous cell tumors and various measures of solar radiation was evaluated for 2,775 contemporaneous Hereford cattle. The animals were from 34 herds located in 21 states in the United States and in one Canadian province. Examinations and photographs were made of the eyes of all cows and heifers in a herd; 33 herds were examined between June and August 1957 and 1 herd was examined in 1958. Solar radiation was measured by altitude and mean annual hours of sunshine applying to an individual herd, and global radiation, a cloudiness index, and elevation of nearby National Weather Service stations. All measures of solar radiation provided evidence of a significant association between increasing risks of developing cancer eye and increasing levels of radiation; adjustments were made for possible confounding effects of age and corneoscleral pigmentation. Associations were evident whether affliction was defined as the occurrence of any type of tumor (ie, plaque, papilloma, or carcinoma), or as the occurrence of only papilloma or carcinoma. Average ages of affected cattle also tended to be lower at high radiation levels than at low levels, further supporting the hypothesis that solar radiation has an important role in the development of this disease. In view of the heritability of eye pigmentation and its inhibitory effect on lesions, cancer eye may be controlled by selective breeding for increased pigmentation in and around the eye to afford protection against the harmful effects of incident UV radiation. PMID- 1854108 TI - Aminophylline therapy for acute bronchospastic disease in the emergency room. AB - OBJECTIVE: To assess the role of aminophylline in the treatment of acute exacerbations of bronchospastic disease when used in addition to inhaled beta agonists and intravenous corticosteroids. DESIGN: Randomized, double-blind, placebo-controlled intervention study. PATIENTS: One hundred thirty-three adult patients with either asthma or chronic obstructive pulmonary disease who presented to the emergency department with asthma or wheezing. INTERVENTIONS: All patients received therapy with both aerosolized metaproterenol and intravenous methyl-prednisolone. Patients were randomly assigned to receive either a loading dose of aminophylline followed by a routine infusion (n = 65) or an equal volume of placebo as a loading dose and infusion (n = 68). MEASUREMENTS AND MAIN RESULTS: At discharge from the emergency department, the median serum theophylline concentration for the aminophylline group was 54 mumol/L (9.7 mg/L). The two groups showed no differences (P greater than 0.2) in measurements of forced expiratory volume at 1 second (FEV1), forced vital capacity (FVC), or peak expiratory flow rate (PEFR) at baseline or at 60 or 120 minutes after aminophylline administration. Neither patient satisfaction nor physician assessment of response to therapy differed between the two groups. There was no difference (P greater than 0.2) in the frequency of side effects, except for a trend toward a higher frequency of nausea (P = 0.13) in the aminophylline group. There was, however, a threefold decrease in the hospital admission rate for patients treated with aminophylline (6%) compared with placebo recipients (21%) (P = 0.016). CONCLUSION: Aminophylline, in doses producing levels just below the commonly accepted therapeutic range, appears to decrease hospital admissions in patients with acute exacerbation of asthma or chronic obstructive pulmonary disease. This finding, if confirmed in larger studies, may represent a substantial cost savings. PMID- 1854109 TI - Comparison of an aggressive (U.S.) and a less aggressive (Canadian) policy for cholesterol screening and treatment. AB - OBJECTIVE: To determine the point at which adverse quality-of-life effects engendered by an aggressive cholesterol-lowering strategy dictate the use of a less aggressive approach. DESIGN: Decision analysis was used to compare the effects of the National Cholesterol Education Program (NCEP) guidelines, an aggressive program, with those of the Canadian Task Force on the Periodic Health Examination (CTF) guidelines, a more conservative program. Quality-adjusted life expectancy was calculated for a theoretical cohort of middle-aged men treated according to each program using Markov cohort analysis. MEASUREMENTS: Guidelines were applied to the population of the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT), under the assumption that cholesterol levels had the distribution of the age- and sex-matched general population. Outcomes were calculated using a three-state (health, coronary heart disease, and death) Markov model. State transition probabilities were calculated using bivariate (age and cholesterol) proportional hazards and logistic regression functions. MAIN RESULTS: The result was a "toss-up"; the number of expected quality-adjusted life years was similar for both programs at all time intervals, although the conservative program was consistently slightly favored. The result was very sensitive to the disutility of dietary therapy (threshold value, 0.0014 compared with the baseline estimate of 0.02) but was also affected by the time frame of the analysis and the rate at which adverse effects of treatment decline. CONCLUSIONS: Even small disutilities associated with treatment may outweight the benefits of aggressive cholesterol-lowering strategies. Research should be directed toward measuring these disutilities and finding ways to reduce their size. Incorporation of the disutility of treatment into policy formulation may result in less interventionist and less costly policies. PMID- 1854110 TI - Effect of triple therapy (antibiotics plus bismuth) on duodenal ulcer healing. A randomized controlled trial. AB - OBJECTIVE: To determine whether antimicrobial therapy for Helicobacter pylori infection accelerates the healing of duodenal ulcers. DESIGN: Single-blind, randomized, controlled trial. SETTING: Veterans Affairs hospital. PARTICIPANTS: One hundred and five patients with endoscopically verified duodenal ulcers. INTERVENTION: Patients received either ranitidine, 300 mg/d, or ranitidine, 300 mg/d, plus "triple therapy" (2 g/d of tetracycline, 750 mg/d of metronidazole, and 5 or 8 bismuth subsalicylate tablets per day). Triple therapy was administered for only the first 2 weeks of ulcer treatment. MEASUREMENTS: Videoendoscopic assessment of ulcer status was done until ulcer healing was complete. Evaluations were done after 2, 4, 8, 12, and 16 weeks of therapy. MAIN RESULTS: Ulcer healing was more rapid in patients receiving ranitidine plus triple therapy than in patients receiving ranitidine alone (P less than 0.01). The cumulative percentages of patients with healed ulcers in the group receiving ranitidine plus triple therapy and in the group receiving ranitidine alone were as follows: 37% and 18% after week 2; 74% and 53% after week 4; 84% and 68% after week 8; 96% and 80% after week 12; and 98% and 84% after week 16. CONCLUSION: Combined therapy with anti-H. pylori agents and ranitidine was superior to ranitidine alone for duodenal ulcer healing. Our results indicate that H. pylori plays a role in duodenal ulcer disease. PMID- 1854111 TI - Cocaine and chest pain: clinical features and outcome of patients hospitalized to rule out myocardial infarction. AB - OBJECTIVE: To investigate the clinical features, electrocardiographic findings, and hospital course in patients admitted with acute chest pain temporally related to cocaine use. DESIGN: Retrospective data analysis. SETTING: A 485-bed county hospital. PATIENTS: One hundred and one consecutive patients with cocaine-related chest pain admitted to the hospital to rule out myocardial infarction. MEASUREMENTS AND MAIN RESULTS: The quality of the chest pain frequently suggested myocardial ischemia. Dyspnea was common (56%). The onset of chest pain occurred during cocaine use in 21% of patients, within 1 hour of use in 37%, and after 1 hour of use in 42%. Admission electrocardiographic findings were interpreted as normal in 32% of patients; as acute myocardial injury in 8%; as early repolarization variant in 32%; as left ventricular hypertrophy in 16%; and as "other" in 12%. Forty-three percent of patients had ST-segment elevation meeting the electrocardiographic criteria for use of thrombolytic therapy, but such elevation was usually due to the early repolarization variant. The initial total creatine kinase was elevated more than 3.3 mu kat/L (200 U/L) in 43% of patients, and an elevated total creatine kinase was recorded at some time during the hospital course in 47% of patients. The creatine kinase MB fraction was less than 0.02 in all patients. Myocardial infarction was ruled out in all patients. No patient experienced in-hospital cardiovascular complications. CONCLUSION: The quality of acute chest pain related to cocaine use is indistinguishable from that experienced in acute myocardial ischemia. Abnormal or normal variant electrocardiographic findings are common in patients with chest pain related to cocaine use, but nevertheless the incidence of acute myocardial infarction is low. The ST-segment and T-wave changes can mimic acute myocardial injury and are most likely normal findings in young black men that can be readily recognized in the emergency department. Most of these patients do not require admission to an intensive care unit. PMID- 1854112 TI - Fluconazole treatment of persistent Cryptococcus neoformans prostatic infection in AIDS. PMID- 1854113 TI - Hypertension in women: what is really known? The Women's Caucus, Working Group on Women's Health of the Society of General Internal Medicine. AB - PURPOSE: To determine whether there is sufficient information in the medical literature to guide appropriate treatment of hypertensive women. DATA IDENTIFICATION: Epidemiologic surveys of hypertension, clinical trials of antihypertensive therapy, and studies of selected adverse effects of antihypertensive agents were identified through a computerized search using MEDLINE and by identifying all studies cited in current medical textbooks as supporting evidence for the guidelines for the treatment of hypertensive individuals. All epidemiologic studies selected were cross-sectional or longitudinal, multicenter, population-based surveys. All clinical trials were large, randomized studies comparing one or more antihypertensive agents with a placebo or nonplacebo control group. Epidemiologic studies and clinical trials were reviewed to assess the quantity and quality of information available regarding important aspects of hypertension in women. Data pertaining to epidemiology, natural history, results of treatment, and two significant side effects of antihypertensive treatment were examined. RESULTS OF DATA ANALYSIS: The prevalence of hypertension is greater in black women than in black men and is about equal in white women and men. Because women outnumber men in the population, there are more hypertensive women than men. The attributable risk percent (the proportion of end points that could be eliminated by removing hypertension) for cardiovascular complications of hypertension is higher for women than men. Clinical trials show clear benefit of therapy for black women but no clear benefit for white women; some studies suggest that treatment of white women is harmful. Lipid profiles and their relation to ischemic heart disease differ for women and men; there is currently no information on the effects of antihypertensive agents on serum lipids in women. Few data have been published on the frequency of sexual dysfunction in treated hypertensive women. CONCLUSIONS: Hypertension in women and its related cardiovascular outcomes are a major public health problem. Clinical trials of antihypertensive therapy do not fully support current guidelines for the treatment of hypertensive women. Research concerning adverse effects of antihypertensive agents has largely excluded women from consideration; further studies are required to guide appropriate treatment. PMID- 1854114 TI - Biologic response modifiers in primary immunodeficiency disorders. AB - OBJECTIVE: To propose a new classification for the primary immunodeficiency disorders and to review potential therapeutic applications of biologic response modifiers in these disorders. DATA SOURCE: Relevant articles were identified through a search of MEDLINE using the following indexing terms: primary immunodeficiencies (and subclassifications), and human immunomodulators (and subclassifications). STUDY SELECTION: Articles were critically reviewed and included if relevant. DATA SYNTHESIS: The primary immunodeficiency disorders are classified according to functional abnormalities, specifically, abnormalities in early cellular maturation, differentiation, regulatory cell function, enzymatic function, and cytokine responses. Such a classification clarifies the potential role of biologic response modifiers in primary immunodeficiency disorders. Intravenous gammaglobulin and histamine-2 (H2)-receptor blockers modify regulatory cell function; retinoids modify abnormal cellular differentiation, gene transfer and enzyme replacement can be applied in disorders characterized by specific functional gene abnormalities; and interferons modify abnormal cytokine responses. Interleukin-2, thymic hormones, transfer factor, and levamisole appear to affect multiple functional defects. CONCLUSIONS: Biologic response modifiers are currently important ancillary tools in the treatment of immunodeficiency disorders, and their therapeutic role will become even more important in the future. Multi-center cooperative trials of new and existing agents are needed to fully define their roles and efficacy in the treatment of these disorders. PMID- 1854115 TI - The U.S. and Canadian health care systems: views of resident physicians. AB - OBJECTIVE: To evaluate U.S. and Canadian resident physicians' views about their health care systems. DESIGN: Self-administered questionnaire survey in 1989. PARTICIPANTS: Senior family medicine and internal medicine residents in Canada and in ten geographically representative American states. MAIN RESULTS: American and Canadian residents had similar levels of professional satisfaction and almost universally agreed on the ethical obligation to provide care to persons of all social circumstances, but U.S. residents were more likely to perceive a serious access problem in their country (75% compared with 18%) and to think that current controls on the medical profession interfere with patient care (81% compared with 58%; P less than 0.001). In addition, U.S. residents were more likely than Canadian residents to believe that primary care salaries were too low (78% compared with 38%) and that salaries of medical subspecialists (57% compared with 17%) and surgeons (85% compared with 28%) were too high. In general, residents preferred their own country's predominant health care system. Whereas 87% of U.S. physicians supported private fee-for-service health care, 85% of Canadian physicians supported government-funded national health insurance. Nonetheless, 42% of U.S. physicians supported and only 17% strongly opposed national health insurance as an alternative approach. About two thirds of respondents from both countries opposed a salaried national health service. CONCLUSIONS: American residents perceived greater problems with access, overall intrusions into medical practice, and fee disparities than did their Canadian counterparts. They preferred private fee-for-service health care, but few strongly opposed government-funded national health insurance as an alternative approach to the health care needs of the United States. PMID- 1854116 TI - Scientific evidence versus therapeutic demand: the introduction of the sulfonamides revisited. AB - Because of recent changes in Federal Food and Drug Administration (FDA) regulations, new medications may now be marketed before completion of rigorous controlled testing. In order to understand the ramifications of this development, it is instructive to recall the introduction of the sulfonamides in the 1930s. The sulfonamides, the first effective antibacterial agents, were marketed in an era of relatively few regulations. Although investigators at times designed controlled trials to evaluate use of the drugs, both researchers and practitioners generally prescribed them for severe infections, despite a lack of conclusive data as to their efficacy. The clinical usefulness of sulfonamides for a given condition often became known through uncontrolled case studies and comparisons with historical control groups. Given the relaxation of FDA regulations, this method of drug evaluation may again become more commonplace. PMID- 1854117 TI - Discoveries. PMID- 1854118 TI - Methylxanthines in the treatment of asthma: the rise, the fall, and the possible rise again. PMID- 1854119 TI - Guidelines for the detection and treatment of elevated serum cholesterol: which is the baby and which is the bathwater? PMID- 1854120 TI - Markers of coronary disease. PMID- 1854121 TI - AIDS enteropathy. PMID- 1854122 TI - Pneumothorax in AIDS. PMID- 1854123 TI - Digoxin: mythology or evidence? PMID- 1854124 TI - Rigors with vancomycin. PMID- 1854125 TI - Urinary urgency and acute intrarenal bleeding. PMID- 1854126 TI - Cost of treating travelers' diarrhea. PMID- 1854127 TI - The doctor's role in wartime. PMID- 1854128 TI - [Screening of asymptomatic pulmonary embolisms by systematic scintigraphy in apparently uncomplicated phlebitis]. AB - To evaluate the presence of asymptomatic pulmonary emboli, a prospective study was conducted in 21 patients with radiologically confirmed phlebitis. Systematic screening by means of radioisotope perfusion lung scanning revealed 8 pulmonary emboli (38%), 6 of which were confirmed by pulmonary angiography (28% using this criterion). In 3 of these patients, the cutoff affected more than 60% of the lung. All the patients remained asymptomatic throughout the study. It is our opinion that the presence of a latent pulmonary embolus should modify the therapeutic approach. In addition to screening for asymptomatic pulmonary emboli, systematic radioisotope perfusion scanning will enable the compilation of a reference document useful in the interpretation of clinical events arising during treatment. PMID- 1854129 TI - [Localization of pheochromocytomas by 131-I-meta-iodobenzylguanidine scintigraphy]. AB - Scintigraphy using 131I-labeled meta-iodobenzylguanidine was performed in 89 patients. A diagnosis of pheochromocytoma was indicated by urinalysis in 28 cases and confirmed histologically in the 27 patients who underwent surgery. The tumor was located using scintigraphy and computed tomography. Fourteen isolated and 6 malignant metastatic pheochromocytomas were found as well as 8 pheochromocytomas associated with genetic disease. Scintigraphy located the tumors in 22 out of 28 cases; however, 3 adrenal pheochromocytomas and 3 malignant pheochromocytomas were not detected. Radioisotope perfusion scanning was more sensitive than computed tomography for the detection of bilateral adrenal pheochromocytoma. In the only case of a multifocal tumor, a combination of scintigraphy and computed tomography located all pheochromocytomas which were later resected. The high number of patients without elevated urine catecholamines and in whom scintigraphy did not alter the diagnosis shows that his technique should be applied only after demonstration of catecholamine hypersection. PMID- 1854130 TI - [Preventive non-estrogenic therapies of post-menopausal osteoporosis]. PMID- 1854131 TI - [Hashimoto's disease and hyperthyroidism]. PMID- 1854132 TI - [Early treatment of human immunodeficiency virus infection]. PMID- 1854133 TI - [Myocardial involvement in AIDS. Echographic study in 85 human immunodeficiency virus infected patients]. AB - Histological and echographic studies of HIV-seropositive patients demonstrated the reality of myocardial involvement during the acquired immunodeficiency syndrome. Eight-five seropositive, asymptomatic patients, 55 of them classified as group IV (CDC criteria), were subjected to echocardiography and measurement of the reduction of the left ventricle fraction. An echographic anomaly was found in 8/85 seropositive patients and in 7/55 group IV patients. This affect on left ventricular contractility seems to occur in patients with a low number of CD4+ lymphocytes (p = NS) and is statistically significantly associated with the level of anti-P24 antibodies/antigenemia (absence of antibodies and positive antigenemia) (p less than 0.05). PMID- 1854134 TI - [Visceral leishmaniasis and immunosuppression]. PMID- 1854135 TI - [Liver and human immunodeficiency virus type 1]. PMID- 1854136 TI - [Hepatic involvement in human immunodeficiency virus infection. 104 histologically documented cases]. PMID- 1854137 TI - [Tuberculous meningitis without biological symptoms in AIDS]. PMID- 1854138 TI - [Systemic lupus erythematosus associated with cirrhosis due to alpha-1 antitrypsin deficiency]. PMID- 1854139 TI - [Fatal acute pancreatitis in systemic lupus erythematosus]. PMID- 1854140 TI - [Cavum tuberculosis. Apropos of 2 cases]. PMID- 1854141 TI - [HELLP syndrome: physiopathological and pathogenic uncertainties]. PMID- 1854142 TI - [Apropos of respiratory manifestations of rheumatoid polyarthritis]. PMID- 1854143 TI - [Evaluation of the prognosis of facial paralysis after surgery of acoustic neurinoma by an early Hilger's test]. AB - Surgery for acoustic neuroma is highly risky for the facial nerve. This is why we have tried to assess immediate postoperative facial impairment by performing Hilger's test within the first few hours. Further evolution of the facial function showed the predictive value of Hilger's test as regards facial recovery. Indeed, a difference greater than 2 mA as compared with the opposite side indicates a lack of facial recovery at the 3rd postoperative month. In addition, facial muscle testing performed within the first postoperative 72 hours makes the prognosis of facial function recovery possible. Lack of facial recovery at the 3rd postoperative month was observed for neuromas with a diameter exceeding 2 cm. Preoperative assessment of the risk of facial sequellae is fundamental and essentially depends on the size of the tumor and on the surgical approach. Intraoperative facial monitoring allows better ensuring the preservation of the VIIth cranial nerve and consequently improves postoperative function. PMID- 1854144 TI - [Unusual circumstances of disclosure of acoustic neurinoma]. AB - While progressive unilateral deafness remains the most typical symptom of the development of acoustic neuroma, the study of at least 1,200 cases operated since 1966 shows that in at least 16.5% of all cases, the triggering signal to seek medical advice was either otologic but atypical, or non-otologic but including symptoms in another pair of cranial nerves, or without any apparent relationship with the area showing a tumor of the eight pair, or even occurring under etiological circumstances that were misleading at first. PMID- 1854145 TI - [Culture of the epithelium of middle ear in the study of seromucous otitis]. AB - Preliminary results on transport properties of middle ear epithelium in primary culture are reported. Primary cultures of Mongolian gerbil (Meriones unguiculatus) middle ear epithelial cells were undergone. These cells formed polarized monolayers that exhibited domes when grown to confluence on non porous support. Domes are the consequence of active transepithelial transports of solutes and water. On porous support, Na+ and Cl- accumulated in the basal bath and generated a basolateral hyperosmolarity that drove a net water flow. This solutes and water absorption was the consequence of an active Na+ transcellular transport, by means of apical sodium channels, that was responsible for the transepithelial potential difference, lumen negative: -39 +/- 1.2 mV (mean +/- SEM, n = 63). Transport of fluid and ions in the middle ear cavities could play a major role in keeping the cavities fluid-free and air-filled and modulating the mucociliary clearance. Modulation of these transports could be involved at the start of otitis media with effusion, and would contribute to the mucociliary clearance impairment. PMID- 1854146 TI - [Presentation of a 16-filter hearing aid with selective amplification and compression]. AB - The hearing aid device is a 4 X 10 X 15 cm box. It is battery operated and monitored by a PC computer. The Texas 320C25 microprocessor performs real-time signal analysis at 16 kHz and gives 16 energy levels ranging from 0 to 8 kHz by Fourier transform. For each frequency band, the energy received is multiplied by a gain determined according to the patient's audiometric characteristics stored in the device's memory. The signal is then synthesized by reverse Fourier transform and sent to the earphone. The performances of this device are discussed and compared with present hearing aid devices. PMID- 1854147 TI - [Hazards and complications of ethmoidal surgery]. AB - The most important publications concerning the complications following transnasal ethmoid surgery are reviewed by the authors who underline the dangers in this type of surgery: meninges, the orbit and orbital elements especially the muscles, the extra-orbital portion of the optic nerve and the internal carotid artery. A great prudence during surgical procedure is emphasized as well as the necessity of a perfect knowledge in scannographic and endoscopic anatomy of ethmoid to avoid the inflation of these complications. PMID- 1854148 TI - [Therapeutic strategy for cervicofacial lymphangioma in children]. AB - The authors report a series of 22 cervicofacial lymphagiomas treated from 1984 to 1990, and try to define a therapeutic strategy. In 11 cases, facial, laryngeal or pharyngeal extension was observed, and 1 cas showed mediastinal extension. These cases are not easily treated, and it is impossible to perform complete surgery, thus leading to recurrence. Tracheotomy was necessary in two cases. In 5 cases, the extension was limited to the cervical area and surgical exeresis was considered complete. Sclerosing injections gave variable results. PMID- 1854149 TI - [Value of cricoid split in congenital subglottic stenoses]. AB - The authors report about the cases of two infants less than 5 weeks old, who presented with congenital subglottic stenosis and in whom a cricoid split produced good results. This procedure, which is classically reserved for difficult extubation of infants due to acquired subglottic stenosis, is compared with the other surgical techniques used in the congenital condition. It may be useful in the latter case owing to its simplicity and to the possibility of performing laryngoplasty later in case of failure. PMID- 1854150 TI - [Sinusitis of the middle turbinate. Descriptive study and treatment]. AB - The middle turbinate inflammatory disease is a well a clinical as a radiological reality which is often unknown because of the rich sinusal surrounding diseases. This pathology represents less than 2% of the total sinusal pathologies we meet daily, and it always occurs on a concha bullosa: the middle turbinate becomes a real sinusal cavity with its own diseases. The new methods of diagnosis, nasal endoscopy and CT scanning, let identifie this turbinal own pathology better than ever. The authors emphasize a surgical treatment. PMID- 1854151 TI - [Difficult intubations. A prospective study]. AB - A prospective tubing of tracheal tubing in view of general anesthia was performed in 441 adults undergoing scheduled surgery. Before surgery, the anesthesists and ENT specialists tried to independently predict the cases of difficult tubing, according to different criteria. Tubing actually was difficult in 38 patients (8.6u) instead of the 21 (55.2%) expected by the ENT specialists and/or the anesthesists. These difficulties were solved by bronchoscopy, which allowed tubing to be performed with a guide-probe (3 cas), by scheduled fiberendoscopy (6), tracheotomy (1), nasotracheal tubing (1), spontaneous ventilation (2), and orotracheal tubing in 25 cases. Current knowledge of the predictive criteria is incomplete: anesthesists must be aware of the assistance techniques required in case of difficult tubing in a non-ENT context. PMID- 1854152 TI - [Benign adenoma of the middle ear]. AB - Starting from one case, the authors review the recent literature data on this very rare lesion. Elements of clinical and histological diagnosis are discussed. Treatment is surgical and must be complete to prevent recurrence. PMID- 1854153 TI - [Tumors of the cerebellopontine angle. Fortuitous association of meningioma and neurinoma]. AB - The authors report the case of a totally accidental meningioma/neuroma association in the same internal auditory meatus, although no Recklinghausen's disease seems to be involved. In relation with this case and with the literature data, the authors review the frequency and diagnosis of meningiomas of the cerebellopontine angle. Lastly, this case helps avoiding a diagnostic error, since the imaging may lead to diagnose one tumor only. PMID- 1854154 TI - [Liposarcoma of the infratemporal fossa. Apropos of a case]. AB - The authors report about one female patient with a liposarcoma of the right infratemporal fossa. Such tumors are rare, making up 10 to 12% of all soft-tissue sarcomas. Their occurrence in a cervical site is rare, unlike that in the inguinal region, the retroperitoneum or the lower limbs. Their diagnosis is mainly established by the histopathological study. Computed tomography and magnetic resonance imaging are particularly useful to choose the surgical approach. The technique chosen for this infratemporal tumor was a transmandibular cervical approach. Evolution was favorable, and the patient has currently had no reoccurrence after two years. PMID- 1854155 TI - High-level resistance to cefotaxime and ceftazidime in Klebsiella pneumoniae isolates from Cleveland, Ohio. AB - Two isolates of Klebsiella pneumoniae possessing both TEM-1 and SHV-2 beta lactamases were isolated from patients at the Cleveland Clinic in 1988. The beta lactamases were discriminated and identified by using substrate hydrolysis data and an isoelectric focusing procedure in which the gel was overlaid with beta lactamase inhibitors. PMID- 1854156 TI - Effect of staggered dose of calcium on the bioavailability of ciprofloxacin. AB - The effect on ciprofloxacin's bioavailability (F) of calcium carbonate given 2 h before ciprofloxacin administration in 12 male volunteers was studied. The relative F with calcium was 0.98, maximum concentration of drug in serum increased significantly from 1.98 to 2.42 mg/liter (P = 0.039), and time to maximum concentration of drug in serum decreased from 1.82 to 1.26 h (P = 0.038). Thus, a single calcium carbonate dose, administered 2 h before ciprofloxacin, does not alter the F of this quinolone. PMID- 1854157 TI - MICs and MBCs of chemotherapeutic agents against Renibacterium salmoninarum. AB - The efficacies of 21 chemotherapeutic agents for controlling bacterial kidney disease were evaluated. The bactericidal and/or bacteriostatic effects of these drugs were tested against 11 Renibacterium salmoninarum strains with different origins. The most effective compounds displaying both bacteriostatic and bactericidal activity for all the isolates were tetracycline and erythromycin, with MICs ranging from less than 0.62 to 10.95 micrograms/ml for tetracycline and from less than 0.62 to 5.47 micrograms/ml for erythromycin. Whereas tetracycline showed identical MICs and MBCs, erythromycin showed bactericidal effects at concentrations of 5.47 to 21.87 micrograms/ml. Similarly, cefazolin and tiamulin proved to be very effective bactericidal compounds against the majority of R. salmoninarum isolates, with MBCs for 90% of the strains tested of 21.87 and 10.95 micrograms/ml, respectively. Neither nitrofuranes, quinolones, nor sulfonamides showed inhibitory effects on the growth of the strains. PMID- 1854158 TI - Lack of ciprofloxacin ototoxicity after repeated ototopical application. AB - The possible side effects of ototopically applied ciprofloxacin on inner ear function were investigated. The hearing function of pigmented guinea pigs was evaluated by daily frequency-specific evoked response audiometry after repeated application of the drug to both ears. Ciprofloxacin appeared to have no statistically significant effect on the hearing thresholds of the experimental animals. PMID- 1854159 TI - Plasmid-encoded fosfomycin resistance. PMID- 1854160 TI - Pharmacokinetics of 3'-azido-3'-deoxythymidine and its catabolites and interactions with probenecid in rhesus monkeys. AB - The pharmacokinetics and metabolism of 3'-azido-3'-deoxythymidine (AZT) were investigated in rhesus monkeys after subcutaneous administration of 33.3 mg of AZT per kg of body weight alone or in the presence of 100 mg of probenecid per kg. In addition to unchanged drug, two catabolites, 5'-O-glucuronide (GAZT) and 3'-amino-3'-deoxythymidine (AMT), were detected in plasma within 30 min. GAZT exhibited a kinetic profile similar to that of AZT, with an elimination half-life of approximately 1 h, while AMT was more variable, with an apparent half-life of 1.6 +/- 1.5 h. Approximately 90% of the total administered dose was recovered in urine within 24 h as AZT, GAZT, AMT, and the 5'-O-glucuronide of AMT. AZT and AMT demonstrated similar cerebrospinal fluid (CSF) penetration 1 h after AZT treatment, while GAZT poorly crossed the blood-brain barrier. Concomitant administration of probenecid greatly altered the pharmacokinetics of AZT, GAZT, and AMT, resulting in prolongation of their apparent elimination half-lives, increased concentrations in plasma, and marked reduction in renal clearances. In addition, the CSF/plasma concentration ratios for AZT and its catabolites were greatly increased, suggesting that probenecid inhibits efflux of AZT and its catabolites from CSF to plasma. The substantial levels of AMT in plasma suggest that this catabolite affects the pharmacodynamic properties of AZT in relation to its activity against human immunodeficiency virus replication and cytotoxicity to host cells. Enhanced AMT levels in plasma in the presence of probenecid may decrease the therapeutic efficacy of the AZT-probenecid combination. PMID- 1854161 TI - Tetracycline resistance heterogeneity in Enterococcus faecium. AB - The tetracycline (Tet) determinants, which encode resistance either to tetracyclines without minocycline (Tcr) or to tetracyclines including minocycline (Tcr-Mnr), of 30 wild-type clinical isolates of Enterococcus faecium were identified and localized. The Tet determinants were transferred by conjugation into a plasmid-free Enterococcus faecalis recipient at frequencies of 10(-6) to 10(-9) transconjugants per donor, as follows: Tcr, 6 strains; Tcr-Mnr, 14 strains; both Tcr and Tcr-Mnr, 6 strains; no detectable transfer, 4 strains. Classes L (Tcr phenotype) and M and O (Tcr-Mnr phenotype) of the Tet determinants were identified by DNA-DNA hybridization experiments. The Tet L determinant was plasmid-borne in 18 strains and was chromosomal in 2 strains. Tet M was chromosomal in 27 strains and plasmid-borne (pIP1534) in 1 strain; pIP1534 also carried Tet L. Tet M was located on Tn916-like elements in 22 strains and on a Tn916-modified element in 1 strain. Tet O was detected in only one strain in which it was plasmid-borne. Both Tet L and Tet M determinants were carried by 19 strains. One strain carried, in addition to chromosomal nonconjugative Tet L and Tet M determinants, a conjugative Tcr-Mnr marker which did not correspond to any Tet determinant tested in this study. These results attest to the genetic complexity of tetracycline resistance in E. faecium strains. PMID- 1854162 TI - Role of the beta-lactamase of Campylobacter jejuni in resistance to beta-lactam agents. AB - We studied the role of the beta-lactamase of Campylobacter jejuni in resistance to beta-lactam agents. beta-Lactamase-positive strains were more resistant than beta-lactamase-negative strains to amoxicillin, ampicillin, and ticarcillin (P less than 0.05). With penicillin G, piperacillin, imipenem, and six cephalosporins, the susceptibility levels were similar for both beta-lactamase positive and -negative strains. By using spectrophotometric and microbiological assays, the beta-lactamase from three strains hydrolyzed ampicillin, amoxicillin, penicillin G, cloxacillin, and, partially, cephalothin. Ticarcillin and piperacillin were partially hydrolyzed in the microbiological assay. There was no activity against five other cephalosporins or imipenem. Isoelectric focusing of the enzyme showed a pI of 8.8. Tazobactam was the best inhibitor of the enzyme, followed by clavulanic acid, sulbactam, and cefoxitin, while EDTA and p chloromercuribenzoate had no activity. All beta-lactamase-positive strains became susceptible to amoxicillin and ampicillin with 1 micrograms of clavulanic acid per ml. With the same inhibitor, there was a reduced but significant effect for ticarcillin but no effect for penicillin G or piperacillin. Sulbactam had no effect and tazobactam was effective only at 2 micrograms/ml on amoxicillin and ampicillin. The beta-lactamase of C. jejuni seems to be a penicillinase with a role in resistance for only amoxicillin, ampicillin, and ticarcillin. PMID- 1854163 TI - Mercuric reductase activity and evidence of broad-spectrum mercury resistance among clinical isolates of rapidly growing mycobacteria. AB - Resistance to mercury was evaluated in 356 rapidly growing mycobacteria belonging to eight taxonomic groups. Resistance to inorganic Hg2+ ranged from 0% among the unnamed third biovariant complex of Mycobacterium fortuitum to 83% among M. chelonae-like organisms. With cell extracts and 203Hg(NO3)2 as the substrate, mercuric reductase (HgRe) activity was demonstrable in six of eight taxonomic groups. HgRe activity was inducible and required NADPH or NADH and a thiol donor for optimai activity. Species with HgRe activity were also resistant to organomercurial compounds, including phenylmercuric acetate. Attempts at intraspecies and intragenus transfer of HgRe activity by conjugation or transformation were unsuccessful. Mercury resistance is common in rapidly growing mycobacteria and appears to function via the same inducible enzyme systems already defined in other bacterial species. This system offers potential as a strain marker for epidemiologic investigations and for studying genetic systems in rapidly growing mycobacteria. PMID- 1854164 TI - Comparative efficacies of ciprofloxacin, amoxicillin, amoxicillin-clavulanic acid, and cefaclor against experimental Streptococcus pneumoniae respiratory infections in mice. AB - Experimental respiratory infections were established in mice by intranasal inoculation of Streptococcus pneumoniae. Inoculation of 10(7) CFU of either S. pneumoniae 1629 or S. pneumoniae 7 produced a fatal pneumonia in nontreated mice 2 to 3 days after infection. Oral therapy was commenced 1 h after infection and was continued three times a day for 2 days. The doses used in mice produced peak concentrations in serum and lung tissue similar to those measured in humans. Ciprofloxacin failed to eliminate either strain of pneumococcus from mouse lungs at any of the doses tested (40, 80, or 160 mg/kg of body weight) by the end of therapy (33 h). Mice that received ciprofloxacin at 160 mg/kg were clear of S. pneumoniae 7 5 days later, whereas persistence and regrowth of S. pneumoniae 1629 resulted in the death of 20% of animals treated with ciprofloxacin. Therapy with cefaclor (20 mg/kg) produced an effect similar to that of ciprofloxacin. In contrast, amoxicillin (10 and 20 mg/kg) and amoxicillin-clavulanic acid (10/5 and 20/10 mg/kg) were significantly (P less than 0.05) more effective in eliminating both strains of S. pneumoniae from the lungs by the end of therapy and, by 168 h, had prevented mortality in 80 to 100% of treated animals. The efficacy of ciprofloxacin against these experimental pneumococcal respiratory infections was poor, despite good penetration into lung tissue, and is a reflection of the low in vitro activity of the quinolone against S. pneumoniae, one of the most common pathogens in community-acquired pneumonia. PMID- 1854165 TI - Interface-area-to-volume ratio of interstitial fluid in humans determined by pharmacokinetic analysis of netilmicin in small and large skin blisters. AB - Human pharmacokinetics of netilmicin during multiple dosing were studied in serum and in the fluid of skin blisters with two different ratios of interface area to fluid volume. The kinetics in the blisters followed the serum concentration-time curve with a delay but with a similar elimination half-life of 2.4 h. The kinetics in the 40-microliters blisters followed closely the theoretically calculated concentrations of the peripheral compartment of a two-compartment model. In contrast, the concentrations in the 120-microliter blisters increased less rapidly, lower peaks were achieved, and concentrations decreased with a significantly longer delay. A very similar area-specific flow or clearance rate of 1.6 microliters.h-1.mm-2 was calculated for the interface area between the serum compartment and either the small or large blisters. The observed rapid mass transfer between serum and blister fluid suggests similar oscillations of concentrations in serum and in small interstitial fluid compartments. PMID- 1854166 TI - Standardization of a fluconazole bioassay and correlation of results with those obtained by high-pressure liquid chromatography. AB - An improved bioassay for fluconazole was developed. This assay is sensitive in the clinically relevant range (2 to 40 micrograms/ml) and analyzes plasma, serum, and cerebrospinal fluid specimens; bioassay results correlate with results obtained by high-pressure liquid chromatography (HPLC). Bioassay and HPLC analyses of spiked plasma, serum, and cerebrospinal fluid samples (run as unknowns) gave good agreement with expected values. Analysis of specimens from patients gave equivalent results by both HPLC and bioassay. HPLC had a lower within-run coefficient of variation (less than 2.5% for HPLC versus less than 11% for bioassay) and a lower between-run coefficient of variation (less than 5% versus less than 12% for bioassay) and was more sensitive (lower limit of detection, 0.1 micrograms/ml [versus 2 micrograms/ml for bioassay]). The bioassay is, however, sufficiently accurate and sensitive for clinical specimens, and its relative simplicity, low sample volume requirement, and low equipment cost should make it the technique of choice for analysis of routine clinical specimens. PMID- 1854167 TI - Comparative in vitro antibacterial activity of sparfloxacin (AT-4140; RP 64206), a new quinolone. AB - The in vitro activity of sparfloxacin (AT-4140; RP 64206), a new fluoroquinolone, was compared with those of 10 other agents against 1,222 clinical isolates. Sparfloxacin and ciprofloxacin were the most active quinolones against members of the family Enterobacteriaceae and nonfermenting gram-negative bacilli; sparfloxacin had superior activity against gram-positive cocci in comparison with the activities of ciprofloxacin and the other quinolones tested (norfloxacin, lomefloxacin, and pefloxacin). Among the inhibited strains, several were resistant to the tested beta-lactam antibiotics or to aminoglycosides. The activity of sparfloxacin was not influenced by the medium that was used; lowering of the pH to 5 had a marked effect on the MICs for two strains each of Enterobacter cloacae and Pseudomonas aeruginosa and one strain each of Escherichia coli and Staphylococcus aureus; the MBC of sparfloxacin was within 1 to 2 dilution steps of the MIC for the strains that were tested. PMID- 1854168 TI - Bactericidal effect of amoxicillin on Helicobacter pylori in an in vitro model using epithelial cells. AB - The treatment of Helicobacter pylori with antimicrobial agents has largely been ineffective, and susceptibility results are in disagreement with those obtained by standard in vitro testing. The bactericidal effect of amoxicillin was tested in an in vitro model by using sessile bacteria attached to HEp-2 cells; this bactericidal effect was compared with that against planktonic bacteria. Viable cell counts were performed by standard procedures after 1, 6, and 24 h of contact with the antibiotic at different concentrations. A bactericidal effect (99.9% killing) was observed against sessile bacteria after 24 h with concentrations of only 10, 1, and 0.1 mg/liter, while against planktonic bacteria it was also noted at concentrations of 0.01 and 0.001 mg/liter, and the effect was observed after 6 h with the three highest concentrations. When the results for five strains were studied by analysis of variance at 6 and 24 h, the main variable was the antibiotic concentration, followed by the culture conditions, e.g., planktonic or sessile bacteria, the strain tested, and the time of contact. A decreased pH of 5.4 did not affect the action of amoxicillin. The bactericidal effect of the combination of amoxicillin and metronidazole was additive against sessile H. pylori. PMID- 1854169 TI - Prospective randomized evaluation of ciprofloxacin versus piperacillin plus amikacin for empiric antibiotic therapy of febrile granulocytopenic cancer patients with lymphomas and solid tumors. The European Organization for Research on Treatment of Cancer International Antimicrobial Therapy Cooperative Group. AB - Empiric therapy for febrile granulocytopenic patients is mandatory, but whether monotherapy is a safe alternative and whether fluoroquinolones are useful agents for this indication are still controversial issues. The use of monotherapy with intravenous ciprofloxacin (200 to 300 mg every 12 h) was evaluated against combined therapy with piperacillin plus amikacin in febrile granulocytopenic patients with solid tumor or lymphoma. The study was discontinued prematurely because patients treated with ciprofloxacin had a significantly lower overall success rate than patients treated with piperacillin plus amikacin (31 of 48 patients [65%] versus 48 of 53 patients [91%], P = 0.002). Patients with gram positive coccal bacteremia had a particularly poor outcome: therapy failed for six of eight patients (75%) treated with ciprofloxacin, while therapy failed for none of four patients treated with piperacillin plus amikacin. Death from primary infection during initially randomized protocol therapy occurred in 7 of 48 patients (14.5%) treated with ciprofloxacin and in 3 of 53 (6%) treated with piperacillin plus amikacin. This study does not support the use of this dose of intravenous ciprofloxacin as empiric monotherapy for fever in granulocytopenic patients. PMID- 1854170 TI - Liposomal amphotericin B inhibits in vitro T-lymphocyte response to antigen. AB - The effects of free amphotericin B (as Fungizone) and amphotericin B (AMB) incorporated into liposomes on the proliferation of lymphocytes were determined. Freshly obtained guinea pig and rat antigen-specific lymphocytes were compared with rat T-lymphocyte cell lines cultured for a long period of time. Incorporation of AMB into multilayered vesicles significantly reduced its effect relative to that of Fungizone on cultured T-cell lines, as reported by others for mammalian cells. In contrast, the effects on freshly obtained antigen-specific lymphocytes were different. Fungizone inhibited proliferation of antigen-specific lymph node cells freshly obtained from immunized guinea pigs at fungicidal concentrations, and incorporation into multilayered lipid vesicles did not have much of a protective effect. Higher concentrations of Fungizone were required to inhibit proliferation of fresh rat lymph node cells, but incorporation into multilayered lipid vesicles still did not have much of a protective effect. Some T lymphocytes in the peripheral circulation of guinea pigs and in the lymph nodes of rats were more resistant to liposomal AMB than another more sensitive T lymphocyte population was. Proliferation of lymphocytes in response to mitogens was inhibited less than that in response to specific antigen was. Thus, sensitivity to AMB depended on the species, the strength of the stimulus used to activate the lymphocytes, and on some other property of the lymphocytes, possibly their state of differentiation. Regardless of the reason for the difference in effects on freshly obtained lymph node lymphocytes and cultured line cells, the former may be more relevant to effects in vivo and should be considered in a complete evaluation of the in vivo toxicity of these forms of the drug. Incorporation into sonicated unilamellar vesicles had more of a protective effect, while equimolar drug-lipid complexes had even more of a protective effect. These forms of AMB might have less of an immunosuppressive potential than multilayered vesicles containing low amounts of AMB do. PMID- 1854171 TI - Characterization of a beta-lactamase found in Eikenella corrodens. AB - Eleven strains of Eikenella corrodens with beta-lactamase activity were isolated from a patient with refractory periodontitis who had previously been treated with penicillin antibiotics. These strains were relatively resistant to benzylpenicillin, amoxicillin, and ampicillin (MICs, greater than or equal to 64 micrograms/ml); susceptible to amoxicillin-clavulanate (2:1) (MICs, less than or equal to 4 micrograms/ml); and moderately susceptible to cephalothin and cephaloridine (MICs, 0.12 to 16 micrograms/ml). The addition of 1 microgram of potassium clavulanate, a beta-lactamase inhibitor, per ml resulted in a significant increase in the susceptibilities of these strains to penicillins but not to cephalosporins. Potassium clavulanate had no effect on non-beta-lactamase producing strains. Enzyme production was constitutive since activity was not increased when cells were cultivated in the presence of benzylpenicillin. Enzyme activity was strongly inhibited by potassium clavulanate, sulbactam, and iodine; weakly inhibited by cloxacillin, imipenem, and moxalactam; but not inhibited by aztreonam, EDTA, or p-chloromercuribenzoate. By gel infiltration, the enzyme had an estimated molecular mass of 29 kDa. Isoelectric focusing of the partially purified enzyme gave a major beta-lactamase band at pH 5.50 and a minor band at pH 5.60. Plasmids were not detected in any of the 11 beta-lactamase-positive strains. This enzyme is considered to belong to class 2a of the Bush classification scheme. PMID- 1854172 TI - Comparative activity of macrolides against Toxoplasma gondii demonstrating utility of an in vitro microassay. AB - The utility of spiramycin for preventing transplacental transmission of toxoplasmosis and the efficacy of conventional macrolides against Toxoplasma gondii are subjects of active debate. An in vitro microassay was developed to determine the relative inhibitory activity against T. gondii of 24 conventional macrolides derived from erythromycin and tylosin (14- and 16-membered macrolides, respectively). Macrolides and T. gondii RH tachyzoites were added to monolayers of BT cells grown in 96-well plates. Plates were incubated for 20 h at 37 degrees C, and the growth of T. gondii was then measured by the selective incorporation of [3H]uracil in trichloroacetic acid-precipitable material during an additional incubation of 20 h. Dose-response curves and 50 and 90% inhibitory concentrations (IC50 and IC90, respectively) were determined for each drug. Microscopic examination was performed on stained replicates of the infected monolayers, and the relative toxicities of the drugs for host cells were determined. Spiramycin and tylosin showed only limited activity against T. gondii (IC50 of 20.16 and 20.00 micrograms/ml, respectively). Erythromycin and azithromycin had a better anti-Toxoplasma activity with IC50 of 14.38 and 8.61 micrograms/ml, respectively, whereas drugs like desmycosin, dirithromycin, and roxithromycin had no detectable activity. Although many macrolides inhibited intracellular proliferation of T. gondii, azithromycin was the only macrolide demonstrating prolonged inhibitory activity on the replication of intracellular tachyzoites. We conclude that conventional 14- and 16-membered macrolides often interfere with the growth of, but may not kill, T. gondii RH tachyzoites in vitro. PMID- 1854173 TI - In vitro activity and in vivo efficacy of a new series of 9-deoxo-12-deoxy-9,12 epoxyerythromycin A derivatives. AB - Analogs of 9-deoxo-12-deoxy-9,12-epoxyerythromycin A with an epimeric hydroxy, amino, or ketone substitution at the 11 position of the macrolide ring and an amino or epimeric hydroxy substitution at the 4" position of the cladinose sugar were synthesized in an attempt to produce acid-stable derivatives of erythromycin with improved bioavailability and activity against gram-negative bacteria. These modifications produced compounds with in vitro activities which were generally similar to that of erythromycin. In mice, however, selected analogs were more active than was erythromycin against staphylococci, streptococci, Haemophilus influenzae, and Legionella pneumophila. In mice, the 11-keto (A-63881), 11 epiamino (A-69334), 11-epiamino-4"-amino (A-71671), and 11-epiamino-4"-epiamino (A-73020) analogs achieved peak concentrations in serum and lung, serum half lives, and/or areas under the serum curve which were greater than those of erythromycin. Improved pharmacokinetics, as compared with those of erythromycin, may explain the increased in vivo antibacterial activities of these compounds. PMID- 1854174 TI - In vitro evaluation of GR69153, a novel catechol-substituted cephalosporin. AB - GR69153 is a C-7 catechol cephalosporin with a broad spectrum of activity against members of the family Enterobacteriaceae (MICs for 50% of strains tested [MIC50s], 0.008 to 0.5 micrograms/ml), Staphylococcus aureus (MIC50, 4 micrograms/ml), Pseudomonas aeruginosa (MIC50, 0.25 micrograms/ml), Haemophilus influenzae (MIC50, 0.03 micrograms/ml), Neisseria gonorrhoeae (MIC50, 0.03 micrograms/ml), and Acinetobacter spp. (MIC50, 2 micrograms/ml). Potent GR69153 activity was also demonstrated against Moraxella catarrhalis, pneumococci, beta hemolytic streptococci, gram-positive anaerobes, and most species of coagulase negative staphylococci. The activity of GR69153 was generally two- to fourfold greater than that of ceftazidime. Resistance level GR69153 MICs for 90% of strains tested (greater than or equal to 32 micrograms/ml) were found most often among Citrobacter freundii, Enterobacter spp. and Morganella morganii strains. GR69153 did not significantly inhibit enterococci, Xanthomonas maltophilia, the Bacteroides fragilis group, Corynebacterium jeikeium, or Listeria monocytogenes. GR69153 was bactericidal and was generally beta-lactamase stable, and MICs were only slightly increased by high inoculum concentrations. Activity was enhanced in an iron-deficient medium, and a modest MIC difference attributed to iron availability was noted between standard agar and broth test results. GR69153 was confirmed to be a potent, catechol-substituted cephalosporin with a spectrum slightly wider than that of ceftazidime, but it was less active than cefpirome or imipenem against some gram-positive pathogens and anaerobes. PMID- 1854175 TI - Amikacin pharmacokinetics in patients receiving high-dose cancer chemotherapy. AB - We retrospectively analyzed amikacin pharmacokinetics in 28 patients (mean age, 47.4 +/- 13.6 years) who received high-dose chemotherapy during a neutropenic febrile episode. Patients received an experimental protocol of high-dose anticancer chemotherapy. Amikacin pharmacokinetic parameters were calculated from two or more concentrations in serum around a single dose by the method of Sawchuck and Zaske (J. Pharmacokinet. Biopharm. 4:183-195, 1976). Predicted parameters were calculated by using standard methods. The observed amikacin volume of distribution and clearance were significantly greater and the elimination half-life was longer than predicted (0.38 +/- 0.13 versus 0.25 liter/kg [P = 0.0001], 1.51 +/- 0.92 versus 1.17 +/- 0.38 liters/h/kg [P = 0.012], and 3.8 +/- 2.4 versus 2.9 +/- 1.1 h [P = 0.011], respectively). Multivariate analysis revealed that albumin correlated negatively and creatinine correlated positively with the volume of distribution and the elimination half life. Creatinine and the percentage below the ideal body weight correlated negatively and hematocrit correlated positively with clearance. Administration of dosage regimens based on predicted pharmacokinetic parameters yielded subtherapeutic amikacin concentrations in serum in our patients. Because of the increased dosage requirements and the need for adequate antibiotic treatment in this population, we suggest guidelines for empiric dosing for patients with advanced cancer receiving intensive chemotherapy. PMID- 1854176 TI - Mechanisms that may account for differential antibiotic susceptibilities among Coxiella burnetii isolates. AB - The Nine Mile, S Q217, and Priscilla isolates, representative of the three major genetic groups of Coxiella burnetii, are known to differ in their susceptibilities to antibiotics. Mechanisms potentially responsible for these differences were investigated. Accumulation of antibiotics by infected L929 cells and purified isolates was measured. In addition, C. burnetii plasmid-transformed Escherichia coli HB101 cells were used to study the possibility that different C. burnetii plasmids are responsible for disparate antibiotic susceptibilities of the isolates. L929 cells recently or persistently infected with the Priscilla isolate exhibited a significantly reduced accumulation of [3H]tetracycline as compared with that in L929 cells infected with either the Nine Mile or S Q217 isolates; accumulation of this drug was greater in cells recently infected each isolate. In contrast, L929 cells recently or persistently infected with the different isolates accumulated [3H]norfloxacin to an equivalent extent. [3H]tetracycline accumulation was approximately the same among the purified isolates. However, as measured by both scintillation and spectrofluorometry, norfloxacin accumulation was significantly diminished in the purified Priscilla isolate. pH had no apparent effect upon isolate permeabilities. The presence of C. burnetii QpH1 or QpRS plasmids did not alter the antibiotic susceptibility of E. coli. Collectively, these results indicate that differential susceptibilities to tetracyclines or fluoroquinolones in C. burnetii isolates may be the result of distinct mechanisms involving altered host-cell (tetracyclines) or isolate specific (fluoroquinolones) permeabilities. PMID- 1854177 TI - Synergistic effects between amoxicillin, metronidazole, and the hydroxymetabolite of metronidazole against Actinobacillus actinomycetemcomitans. AB - Interactions between metronidazole and amoxicillin, metronidazole and its hydroxymetabolite, and amoxicillin and the hydroxymetabolite of metronidazole were investigated with checkerboard titrations in combination with accurately determined MICs and MBCs. Actinobacillus actinomycetemcomitans was used as the test organism. Synergism was found for all three combinations. Fractional inhibitory concentration indices and fractional bactericidal concentration indices varied from 0.3 to 0.7. These synergistic interactions between these antibiotics may explain the efficacy of the combination of metronidazole and amoxicillin in various bacterial infections, including periodontal disease. PMID- 1854178 TI - Comparative evaluation of loracarbef and amoxicillin-clavulanate for acute otitis media. AB - One hundred five infants and children with acute otitis media were randomized to therapy with loracarbef, an experimental carbacephem antibiotic, or amoxicillin clavulanate (Augmentin), an approved drug for this disease. Ninety-two were evaluable (46 in each group). Middle ear fluid samples obtained for culture before therapy grew Haemophilus spp. in 30% of cases, pneumococci in 29% of cases, and Moraxella catarrhalis in 15% of cases. beta-Lactamase-producing bacteria were found in 37% of patients. Clinical failure occurred in four loracarbef-treated patients and one amoxicillin-clavulanate-treated patient (P = 0.361). Recurrence of acute otitis media was more common in the 2 to 3 weeks after loracarbef treatment (eight patients) than it was after amoxicillin clavulanate therapy (three patients), but not significantly so (P = 0.197). Thus, combined failure and recurrence occurred in 12 loracarbef-treated patients and four amoxicillin-clavulanate-treated patients (P = 0.052). Gastrointestinal side effects occurred in 13 loracarbef-treated and 21 amoxicillin-clavulanate-treated patients (P = 0.13). Diaper rash was more common with amoxicillin-clavulanate (22 patients) than with loracarbef (10 patients; P = 0.016). Satisfactory results were achieved with both antibiotics, and adverse effects, although common, were minor. PMID- 1854179 TI - Steady-state pharmacokinetics of intramuscular imipenem-cilastatin in elderly patients with various degrees of renal function. AB - We studied the concentrations in plasma and pharmacokinetics of imipenem and cilastatin in elderly patients (greater than 65 years old) who had various degrees of renal function and who were hospitalized with soft tissue infections. Three groups of patients received imipenem-cilastatin (500/500 mg) intramuscularly every 12 h: group I consisted of eight patients with a creatinine clearance (CLCR) of greater than 50 ml/min (range, 51 to 84 ml/min; mean, 65.8 ml/min); group II consisted of three patients with a CLCR of 20 to 50 ml/min; and group III consisted of two patients with a CLCR of less than 20 ml/min. Imipenem and cilastatin concentrations were measured at steady state on day 5. Mean peak and trough plasma imipenem concentrations were 5.28 +/- 1.78 and 1.43 +/- 0.76 micrograms/ml in group I, 6.25 +/- 0.78 and 2.50 +/- 0.00 micrograms/ml in group II, and 14.3 +/- 0.71 and 6.85 +/- 1.06 micrograms/ml in group III, respectively. Mean peak and trough plasma cilastatin concentrations were 11.8 +/- 2.85 and 0.31 +/- 0.43 microgram/ml in group I, 15.5 +/- 2.48 and 2.03 +/- 2.05 micrograms/ml in group II, and 24.5 +/- 6.72 and 10.7 +/- 5.94 micrograms/ml in group III, respectively. Mean imipenem AUCss (area under the concentration-time curve over a dosage interval at steady state) values were 38.7 +/- 7.9 micrograms.h/ml for group I, 52.3 +/- 7.3 micrograms.h/ml for group II, and 143.7 +/- 11.9 micrograms.h/ml for group III. Mean cilastatin AUCss values were 45.6 +/- 12.5 micrograms.h/ml for group I, 93.8 +/- 51.2 micrograms.h/ml for group II, and 217.5 +/- 57.8 micrograms.h/ml for group III. Cilastatin mean apparent body clearance values (normalized to weight) were 2.78 +/- 0.67 ml/min for group I, 1.43 +/- 0.81 ml/min for group II, and 0.71 +/- 0.24 ml/min for group III. Imipenem open-lactam metabolite levels were all below the level of detective of the assay (<3.9 micrograms/ml). There was a progressive increase in plasma imipenem and cilastatin levels and AUCss and there was a decline in body clearance as renal function declined. PMID- 1854180 TI - Modulation of the intestinal flora of mice by parenteral treatment with broad spectrum cephalosporins. AB - A study was performed to determine the effect of parenteral treatment with four broad-spectrum cephalosporins (cefoperazone, ceftriaxone, ceftazidime, and cefepime) on the number of aerobic gram-negative rods and on the outgrowth of Candida albicans and a multiresistant strain of Citrobacter freundii in the feces of mice. The estimated fractions of a parenteral dose that were excreted into the gastrointestinal tract were 0.37 for cefoperazone, 0.11 for ceftriaxone, 0.03 for ceftazidime, and 0.002 for cefepime. All four cephalosporins significantly decreased the number of aerobic gram-negative rods in the feces, and virtually all gram-negative rods were eliminated at high doses of cefoperazone, ceftazidime, and ceftriaxone. Furthermore, at high doses these three compounds led to a significant increase of the outgrowth of resistant Citrobacter freundii. The outgrowth of Candida albicans was increased at high doses of cefoperazone and ceftriaxone, whereas ceftazidime and cefepime did not have this effect. The most profound changes in the gastrointestinal ecology were observed during treatment with high doses of cefoperazone. The results suggest that the colonization resistance of the gastrointestinal tract can be substantially decreased by parenteral treatment with cefoperazone and, to a lesser extent, with ceftriaxone and ceftazidime. PMID- 1854181 TI - Modulation of the intestinal flora of mice by treatment with aztreonam and tigemonam. AB - Oral and parenteral administration of aztreonam and oral administration of tigemonam to conventional mice caused a decrease in the number of aerobic gram negative rods in the feces. Oral treatment with high doses of aztreonam (greater than or equal to 25 mg/kg/day) and tigemonam (100 mg/kg/day) adversely influenced colonization resistance, whereas oral treatment with lower doses of the monobactams or parenteral treatment with aztreonam did not. PMID- 1854182 TI - Effect of low-level and intermittent minocycline therapy on the growth of Mycobacterium leprae in mice. AB - We evaluated the minimal concentrations of minocycline in the diet and in serum required to inhibit the growth of seven Mycobacterium leprae isolates in mice. Minocycline concentrations of 0.01 and 0.04% in the diet, which resulted in levels in serum of less than or equal to 0.17 and 0.51 microgram/ml, respectively, were consistently and completely inhibitory. Even 0.004% dietary minocycline (levels in serum, less than or equal to 0.08 microgram/ml) partially inhibited five of these strains, while 0.001% minocycline was consistently inactive. For five of these isolates, minocycline at a concentration of 0.04% in the diet given 3 days (Monday, Wednesday, Friday) and 1 day weekly completely inhibited the growth of M. leprae, and minocycline given even 1 day monthly was partially inhibitory for three of these five M. leprae isolates. PMID- 1854183 TI - In vitro susceptibilities of clinical isolates of cysteine-requiring Escherichia coli to 12 antimicrobial agents. AB - The MICs of 12 antimicrobial agents for 42 cysteine-requiring strains of Escherichia coli showed a high concordance when determined on three different media, one of which was supplemented with cysteine. Differences in the MICs of several agents were detected between 18 prototrophic revertants and their parent auxotrophs. A total of 64.7% of the isolates were fully susceptible to all agents, and no particular resistance pattern was evident. PMID- 1854184 TI - Serine proteinase from Staphylococcus aureus enhances elastin degradation by elastases in the presence of human alpha-1-proteinase inhibitor. AB - During staphylococcal pneumonia massive destruction of lung tissue is often observed. Staphylococcal serine proteinase (SSP) inactivates alpha-1-proteinase inhibitor (alpha 1PI) a major factor which protects lungs from phagocyte proteases. We investigated the effect of SSP on elastin degradation by porcine pancreatic elastase (PE) and crude extract of human neutrophil elastase (NE) in solution and gel containing alpha 1PI. SSP having no elastase activity enhanced PE and NE-induced elastinolysis in solution when added to alpha 1PI before mixing with elastase and then with elastin. SSP added simultaneously with alpha 1PI to PE had no influence on elastin degradation. However, SSP added simultaneously, 30 min before or 30 min after PE significantly increased elastin digestion in elastin-agarose plate with alpha 1PI. Maximal increase in elastinolysis about 3 fold was for SSP added 30 min prior to PE. Since elastin is the major component of the alveolar walls it is possible that lung damage in the course of staphylococcal infection may partly depend on action of SSP. PMID- 1854185 TI - Molecular cloning and functional characterization of a recA analog from Pseudomonas stutzeri and construction of a P. stutzeri recA mutant. AB - A recombinant plasmid carrying the Pseudomonas stutzeri recA gene was isolated by complementation of the Escherichia coli recA13 mutation. Subcloning experiments showed that the gene was located on a 1500 bp PvuII-BglII fragment. The cloned gene complements an E. coli recA mutant for resistance to Methylmethanosulphonate (MMS) and UV irradiation. It was also capable of restoring the recombination proficiency in that mutant. The cloned fragment was used to construct a recA deletion mutant of P. stutzeri. This mutant too was shown to be sensitive towards MMS and UV irradiation. The mutant strain was found to be completely deficient in natural transformation with chromosomal DNA, due to the impairment in homologous recombination. PMID- 1854186 TI - Williopsis salicorniae sp. nov. AB - Four strains of an undescribed species of the genus Williopsis were isolated from brackish water. A description of the new species, Williopsis salicorniae (type strain, CBS 8071, NRRL Y-12834), is given. PMID- 1854187 TI - Arxula adeninivorans, a yeast assimilating many nitrogenous and aromatic compounds. AB - A detailed description of the yeast species Arxula adeninivorans (syn. Trichosporon adeninovorans) was given. The yeast assimilated all the sugars, polyalcohols and organic acids used in the conventional carbon compound assimilation test rapidly, except for L-rhamnose, inulin, lactose, lactate and methanol. As nitrogen sources served all conventionally used compounds except creatine and creatinine. Several nitrogenous compounds, e.g. amino acids, purine derivatives, served as sole source of carbon, nitrogen and energy. This was also true of many primary n-alkylamines and terminal diamines, but of nitrogen-less analogous compounds such as alcohols, dialcohols, carboxylic acids and dicarboxylic acids only intermediates of general metabolism were assimilated. For observing growth at the expense of potentially toxic compounds the slant culture method was developed. In this test lactate was readily assimilated but proved to be toxic at the same time. Several aliphatic organic acids and their esters supported growth in this test, as was the case with several benzene compounds such as hydroquinone, 3- and 4-hydroxybenzoic acid, protocatechuic, gentisic, gallic and ferulic acids, 4-hydroxyacetophenone and 1-phenyl-n-dodecane. PMID- 1854189 TI - Septal micropores in Zygozyma and their taxonomic significance. AB - Septal micropores or plasmadesmal canals have been observed in two species of the lipomycetaceous genus Zygozyma. The presence of these canals is considered as further evidence for the connexion between the Lipomycetaceae and the Dipodascaceae. The genus Zygozyma has been emended. PMID- 1854190 TI - Bulleromyces genus novum (Tremellales), a teleomorph for Bullera alba, and the occurrence of mating in Bullera variabilis. AB - Mating is observed in Bullera alba and B. variabilis, resulting in the formation of dikaryotic mycelium with clamps, haustorial branches, and lateral and terminal dikaryotic, clavate, lageniform or subglobose cells. These cells develop in B. alba into tremellaceous phragmobasidia. Karyogamy has been observed in young non divided basidia. Germination of the phragmobasidia occurred by acropetal chains of yeast cells, ballistospores or hyphae. Septal pores are dolipores with parenthesomes made up of U-shaped vesicles (Tremellales type). For the teleomorph of B. alba a new genus, Bulleromyces, is proposed, with only one species, viz. Bulleromyces albus. PMID- 1854188 TI - Oxygen regulated gene expression in Escherichia coli: control of anaerobic respiration by the FNR protein. AB - Molecular oxygen is an important regulatory signal in facultative anaerobic bacteria and controls the expression of a great variety of genes positively or negatively. The expression of anaerobic respiration and of related functions of E. coli is controlled by the positive gene regulator FNR, which activates transcription in the absence of O2. The regulated genes carry a FNR consensus sequence upstream of the promoter. Under the same conditions FNR represses some of the genes of aerobic respiration. The binding to the DNA occurs by an alpha helix-turn-alpha-helix DNA-binding domain. FNR contains 5 cysteine residues, four of which are arranged in a cluster close to the N-terminal end. For the function of FNR as a O2-dependent regulator three of the cysteine residues in the cluster and the residue outside the cluster are essential. FNR binds iron as a cofactor which most likely is involved in the O2-sensing by the protein. The experiments indicate that the cysteine residues are responsible for the binding of the iron. From the protein in vivo two functional states can be differentiated, an aerobic or metal-depleted form and an anaerobic form. Only the anaerobic form acts as a gene activator or repressor. Sensing of O2 or of positive redox potentials by the iron ion is thought to cause the conversion of the two functional states. The FNR protein in addition contains a potential nucleotide binding domain. The significance and function of this site is not clear. PMID- 1854191 TI - Sympodiomycopsis: a new yeast-like anamorph genus with basidiomycetous nature from orchid nectar. AB - A description is provided for a new anamorph genus Sympodiomycopsis (Hyphomycetes), which is neither ballistosporogenous nor sterigmatosporogenous. The genus is typified by S. paphiopedili sp. nov. and accommodates one species which was isolated from nectar of Paphiopedilum primurinum in Japan. Phenotypically, the genus shows some similarity to Sympodiomyces because of the presence of a yeast morph with sympodial conidiogenous cell proliferation, but it is distinguished from that genus morphologically by a yeast morph with the enteroblastic-annellidic conidiogenesis and the conspicuous development of a hyphal morph with holoblastic-sympodial conidiogenous cells, and chemotaxonomically by the ubiquinone system Q-10 and 10% difference in the guanine plus cytosine (G + C) content of the nuclear DNA. Phylogenetically, the type of cell wall and septal pore ultrastructure, and the primary biochemical and chemotaxonomic characters of S. paphiopedili indicate a basidiomycetous affinity. PMID- 1854192 TI - Biodegradation of creosote and pentachlorophenol in contaminated groundwater: chemical and biological assessment. AB - Shake flask studies examined the rate and extent of biodegradation of pentachlorophenol (PCP) and 42 components of coal-tar creosote present in contaminated groundwater recovered from the American Creosote Works Superfund site, Pensacola, Fla. The ability of indigenous soil microorganisms to remove these contaminants from aqueous solutions was determined by gas chromatographic analysis of organic extracts of biotreated groundwater. Changes in potential environmental and human health hazards associated with the biodegradation of this material were determined at intervals by Microtox assays and fish toxicity and teratogenicity tests. After 14 days of incubation at 30 degrees C, indigenous microorganisms effectively removed 100, 99, 94, 88, and 87% of measured phenolic and lower-molecular-weight polycyclic aromatic hydrocarbons (PAHs) and S heterocyclic, N-heterocyclic, and O-heterocyclic constituents of creosote, respectively. However, only 53% of the higher-molecular-weight PAHs were degraded; PCP was not removed. Despite the removal of a majority of the organic contaminants through biotreatment, only a slight decrease in the toxicity and teratogenicity of biotreated groundwater was observed. Data suggest that toxicity and teratogenicity are associated with compounds difficult to treat biologically and that one may not necessarily rely on indigenous microorganisms to effectively remove these compounds in a reasonable time span; to this end, alternative or supplemental approaches may be necessary. Similar measures of the toxicity and teratogenicity of treated material may offer a simple, yet important, guide to bioremediation effectiveness. PMID- 1854194 TI - Development of species-specific hybridization probes for marine luminous bacteria by using in vitro DNA amplification. AB - By using two highly conserved region of the luxA gene as primers, polymerase chain reaction amplification methods were used to prepare species-specific probes against the luciferase gene from four major groups of marine luminous bacteria. Laboratory studies with test strains indicated that three of the four probes cross-reacted with themselves and with one or more of the other species at low stringencies but were specific for members of their own species at high stringencies. The fourth probe, generated from Vibrio harveyi DNA, cross-reacted with DNAs from two closely related species, V. orientalis and V. vulnificus. When nonluminous cultures were tested with the species-specific probes, no false positive results were observed, even at low stringencies. Two field isolates were correctly identified as Photobacterium phosphoreum by using the species-specific hybridization probes at high stringency. A mixed probe (four different hybridization probes) used at low stringency gave positive results with all of the luminous bacteria tested, including the terrestrial species, Xenorhabdus luminescens, and the taxonomically distinct marine bacterial species Shewanella hanedai; minimal cross-hybridization with these species was seen at higher stringencies. PMID- 1854193 TI - Detection of luciferase gene sequence in nonluminescent Vibrio cholerae by colony hybridization and polymerase chain reaction. AB - Bioluminescence is a trait observed among approximately 10% of Vibrio cholerae isolates. We have demonstrated that not only do some strains of V. cholerae produce low levels of light, undetectable by the human eye, but the luciferase gene sequence is present in strains of V. cholerae which emit no detectable light, evidenced by hybridization with a luciferase DNA probe. Comparisons of the amino acid sequences of luciferase enzymes of marine species have shown that these proteins have diverged to the point where they have only short regions of amino acid identity. The polymerase chain reaction method of DNA amplification with oligonucleotide primers based on these regions was used to isolate a region of the luxA gene from both luminescent and nonluminescent V. cholerae strains. The nucleotide sequence of this region was determined and reveals that nonluminescent V. cholerae have 99.7% nucleotide sequence similarity in this region with the luminescent biovar V. cholerae bv. albensis as well as significant similarity to other species of bioluminescent bacteria, a finding that is in accord with the hypothesis that these species have a common luminescent ancestor, most probably from the marine environment. PMID- 1854195 TI - Isolation and characterization of chromosomal promoters of Streptococcus salivarius subsp. thermophilus. AB - A promoter probe vector, pTG244, was constructed with the aim of isolating transcription initiation signals from Streptococcus thermophilus (Streptococcus salivarius subsp. thermophilus). pTG244 is based on the Escherichia coli streptococcus shuttle vector pTG222, into which the promoterless chloramphenicol acetyltransferase gene of Bacillus pumilus (cat-86) was cloned. Random Sau3A fragments from the S. thermophilus A054 chromosomal DNA were cloned upstream of the cat-86 gene by using E. coli as the host. The pool of recombinant plasmids were introduced into S. thermophilus and Lactococcus lactis subsp. lactis in order to search for promoter activity in these hosts. For S. thermophilus, it was necessary to first select erythromycin-resistant transformants and then to screen for chloramphenicol resistance among these. Direct selection of chloramphenicol resistant clones was, however, possible in L. lactis subsp. lactis. Six fragments exhibiting promoter activity were characterized in S. thermophilus by measuring the levels of cat-86 transcription and/or chloramphenicol acetyltransferase specific activity. Three of the promoter-carrying fragments were sequenced. The 5' ends of their corresponding mRNAs were determined by S1 mapping and shown to correspond to a purine residue in all cases. Upstream from these potential transcription start points, sequences homologous to the E. coli sigma 70 and the Bacillus subtilis vegetative sigma 43 (or sigma A) consensus promoters were identified. PMID- 1854196 TI - Enzymatic conversion of norsolorinic acid to averufin in aflatoxin biosynthesis. AB - 5'-Hydroxyaverantin (HAVN) was isolated from a mold, Emericella heterothallica IFO 30842. Aspergillus parasiticus NIAH-26, a UV-irradiated mutant of A. parasiticus SYS-4, produced neither aflatoxins nor precursors in yeast extract sucrose (YES) medium. When the postmicrosome (cytosol) fraction of NIAH-26, which had been prepared from the culture in YES medium, was incubated with norsolorinic acid (NA) in the presence of NADH or NADPH, averantin (AVN) was produced. The reverse reaction from AVN to NA was promoted by the addition of NAD or NADP (dehydrogenase reaction). When the microsome fraction of NIAH-26 was incubated with AVN, HAVN was produced in the presence of NADPH (monooxygenase reaction). HAVN was, furthermore, oxidized to averufin (AVR) by the cytosol fraction of NIAH 26 in the presence of NAD or NADP (dehydrogenase reaction). In the feeding experiments with A. parasiticus NIAH-26, aflatoxins were produced from AVN, HAVN, NA, and AVR but not from averufanin or averythrin. These results indicate that the reaction sequence NA in equilibrium AVN----HAVN----AVR is involved in the biosynthetic pathway of aflatoxins. The enzyme activities described here were dependent on the culture medium, and no enzyme activities were observed in the nonaflatoxigenic strain A. oryzae SYS-2 (IFO 4251). PMID- 1854197 TI - Expression of an L-alanine dehydrogenase gene in Zymomonas mobilis and excretion of L-alanine. AB - An approach to broaden the product range of the ethanologenic, gram-negative bacterium Zymomonas mobilis by means of genetic engineering is presented. Gene alaD for L-alanine dehydrogenase (EC 1.4.1.1.) from Bacillus sphaericus was cloned and introduced into Z. mobilis. Under the control of the strong promoter of the pyruvate decarboxylase (pdc) gene, the enzyme was expressed up to a specific activity of nearly 1 mu mol . min -1 . mg of protein -1 in recombinant cells. As a results of this high L-alanine dehydrogenase activity, growing cells excreted up to 10 mmol of alanine per 280 mmol of glucose utilized into a mineral salts medium. By the addition of 85 mM NH4+ to the medium, growth of the recombinant cells stopped, and up to 41 mmol alanine was secreted. As alanine dehydrogenase competed with pyruvate decarboxylase (PDC) (EC 4.1.1.1.) for the same substrate (pyruvate), PDC activity was reduced by starvation for the essential PDC cofactor thiamine PPi. A thiamine auxotrophy mutant of Z. mobilis which carried the alaD gene was starved for 40 h in glucose-supplemented mineral salts medium and then shifted to mineral salts medium with 85 mM NH4+ and 280 mmol of glucose. The recombinants excreted up to 84 mmol of alanine (7.5 g/liter) over 25 h. Alanine excretion proceeded at an initial velocity of 238 nmol . min-1 . mg [dry weight]-1. Despite this high activity, the excretion rate seemed to be a limiting factor, as the intracellular concentration of alanine was as high as 260 mM at the beginning of the excretion phase and decreased to 80 to 90 mM over 24 h. PMID- 1854198 TI - Cloning, nucleotide sequence, and transcriptional analysis of the NAD(P) dependent cholesterol dehydrogenase gene from a Nocardia sp. and its hyperexpression in Streptomyces spp. AB - NAD(P)-dependent cholesterol dehydrogenases [NAD(P)-CDH], which allow easier quantification of cholesterol by means of directly measuring the A340 of NAD(P)H, are useful for clinical purposes. The amino acid sequences of the NH2 terminus and the fragments obtained by CNBr decomposition of the NAD(P)-CDH from a Nocardia sp. were determined for preparation of synthetic oligonucleotides as hybridization probes. A 4.4-kbp BamHI fragment hybridizing to these probes was cloned on pUC19 in Escherichia coli. The nucleotide sequence together with the determined amino acid sequences revealed that this enzyme consists of 364 amino acids (Mr, 39,792) and contains an NAD(P)-binding consensus sequence at its NH2 terminal portion. High-resolution S1 nuclease mapping suggested that in NAD(P) CDH of both Nocardia and Streptomyces spp. transcription initiates at the adenine residue, which is the first position of the translational initiation triplet (AUG) of this protein. The S1 mapping experiments also showed that cholesterol dependent regulation in the Nocardia sp. occurred at the level of transcription. In Streptomyces lividans containing the cloned fragment, however, this promoter was expressed constitutively. DNA manipulation of the cloned gene in E. coli, including the generation of a ribosome-binding sequence at an appropriate position by oligonucleotide-directed mutagenesis, led to production of this protein in a very large amount but in the enzymatically inactive form of inclusion bodies. On the other hand, a Streptomyces host-vector system was successfully used for producing 40 times as much enzymatically active NAD(P)-CDH as that produced by the original Nocardia sp. PMID- 1854199 TI - Cloning, sequencing, and expression of the N-acyl-D-mannosamine dehydrogenase gene from Flavobacterium sp. strain 141-8 in Escherichia coli. AB - The gene coding for N-acyl-D-mannosamine dehydrogenase (NAM-DH) from Flavobacterium sp. strain 141-8 was cloned and expressed under the control of a lac promoter in Escherichia coli JM109. The DNA sequence of the gene was determined, and an open reading frame encoding a polypeptide composed of 272 amino acid residues (Mr, 27,473) was identified. The E. coli transformants which showed over 200-fold higher NAM-DH activity than did the Flavobacterium strain produced the enzyme as a protein fused with beta-galactosidase. Despite being a fusion, NAM-DH produced by E. coli transformants appeared unchanged in pH optimum, Km, and substrate specificity from Flavobacterium sp. strain 141-8. This newly recombinant enzyme may be applicable to the quantitative determination of sialic acid in serum. PMID- 1854200 TI - Fate of DNA encoding hygromycin resistance after meiosis in transformed strains of Gibberella fujikuroi (Fusarium moniliforme). AB - Stability of foreign DNA transformed into a novel host is an important parameter in decisions to permit the release of genetically engineered microorganisms into the environment. Meiotic instability of transformed DNA has been reported in fungi such as Ascobolus, Aspergillus, and Neurospora. We used strains of Gibberella fujikuroi (Fusarium moniliforme) transformed with the hygr gene from Escherichia coli to study meiotic stability of foreign DNA in this plant pathogenic fungus. Crosses with single-copy transformants segregated hygr:hygs in a 1:1 manner consistent with that expected for a Mendelian locus in a haploid organism. Multicopy transformants, however, segregated hygr:hygs in a 1:2 manner that was not consistent with Mendelian expectations for a chromosomal marker, even though two unrelated auxotrophic nuclear genes were segregating normally. Segregation ratios in crosses in which hygr was introduced via the male parent did not differ significantly from crosses in which the transformed strain served as the female parent. Some of the sensitive progeny from the crosses with the multicopy transformants carried hygr sequences. When these phenotypically sensitive progeny were crossed with a wild-type strain that carried no hygr sequences, some of the progeny were phenotypically hygr. Some progeny from some crosses were more resistant to hygromycin than were their sibs or the transformant strains that served as their parents. Transformants passaged through a maize plant only rarely segregated progeny with the high levels of resistance. The mechanism underlying these genetic instabilities is not clear but may involve unequal crossing over or methylation or both. Further work with cloned genes with homology to sequences already present in the Fusarium genome is warranted. PMID- 1854201 TI - Identification of a specific manganese peroxidase among ligninolytic enzymes secreted by Phanerochaete chrysosporium during wood decay. AB - The specific enzymes associated with lignin degradation in solid lignocellulosic substrates have not been identified. Therefore, we examined extracts of cultures of Phanerochaete chrysosporium that were degrading a mechanical pulp of aspen wood. Western blot (immunoblot) analyses of the partially purified protein revealed lignin peroxidase, manganese-dependent peroxidase (MnP), and glyoxal oxidase. The dominant peroxidase, an isoenzyme of MnP (pI 4.9), was isolated, and its N-terminal amino acid sequence and amino acid composition were determined. The results reveal both similarities to and differences from the deduced amino acid sequences from cDNA clones of dominant MnP isoenzymes from liquid cultures. Our results suggest, therefore, that the ligninolytic-enzyme-encoding genes that are expressed during solid substrate degradation differ from those expressed in liquid culture or are allelic variants of their liquid culture counterparts. In addition to lignin peroxidase, MnP, and glyoxal oxidase, xylanase and protease activities were present in the extracts of the degrading pulp. PMID- 1854202 TI - Designation of Streptomycete 16S and 23S rRNA-based target regions for oligonucleotide probes. AB - The 16S and 23S rRNA of various Streptomyces species were partially sequenced and screened for the presence of stretches that could define all members of the genus, groups of species, or individual species. Nucleotide 929 (Streptomyces ambofaciens nomenclature [J.L. Pernodet, M.T. Alegre, F. Boccard, and M. Guerineau, Gene 79:33-46, 1989]) is a nucleotide highly unique to Streptomyces species which, in combination with flanking regions, allowed the designation of a genus-specific probe. Regions 158 through 203 of the 16S rRNA and 1518 through 1645 of the 23S rRNA (helix 54 [Pernodet et al., Gene 79:33-46, 1989]) have a high potential to define species, whereas the degree of variation in regions 982 through 998 and 1102 through 1122 of the 16S rRNA is less pronounced but characteristic for at least certain species. Alone or in combination with each other, these regions may serve as target sites for synthetic oligonucleotide probes and primers to be used in the determination of pure cultures and in the characterization of community structures. The specificity of several probes is demonstrated by dot blot hybridization. PMID- 1854203 TI - Quantitative assessment of the effects of metals on microbial degradation of organic chemicals. AB - Biodegradation inhibition of a benchmark chemical, 2,4-dichloro-phenoxyacetic acid methyl ester (2,4-DME), was used to quantify the inhibitory effects of heavy metals on aerobic microbial degradation rates of organic chemicals. This procedure used lake sediments and aufwuchs (floating mats) collected in the field or from laboratory microcosms. Effects of CuCl2, HgCl2, ZnCl2, Cd(NO3)2, and Cr(NO3)3 at initial concentrations ranging from 0.3 microM to 73 mM (approximately 0.1 to 10,000 mg liter-1) were investigated. In general, such metallic compounds appeared to be considerably more inhibitory to the biodegradation of an organic chemical than high concentrations of microbially toxic organics studied previously. Effects of various metal concentrations were evaluated based on the following: (i) estimated MICs, (ii) concentrations that caused a significant effect on biodegradation parameters (both a greater than 10% decrease in Vmax and a greater than 10% increase in t1/2 for 2,4-DME degradation), and (iii) concentrations that caused biodegradation half-life doublings (HLDs). The MICs of metals in sediment were lowest for Zn2+ (0.10 microM) and highest for Cd2+ and Cu2+ (0.9 and 1.2 microM, respectively). The MICs of metals in aufwuchs were lowest for Hg2+ (0.01 microM), intermediate for Cu2+ and Zn2+ (0.42 and 0.62 microM, respectively), and highest for Cr3+ and Cd2+ (3.4 and 5.6 microM, respectively). Compared with Cu2+ on aufwuchs, 70 times more Zn2+, 250 times more Cr3+, and 1,000 times more Cd2+ was required to significantly affect aufwuchs biodegradation rate parameters and coefficients (Vmax and t1/2). Aufwuchs was significantly affected by the lowest Hg2+ concentration tested (5 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854204 TI - Polyethylene glycol-induced internalization of bacteria into fungal protoplasts: electron microscopic study and optimization of experimental conditions. AB - We studied the mechanism of internalization of Escherichia coli into Saccharomyces cerevisiae induced by polyethylene glycol (PEG) and optimized the experimental conditions. Transmission electron microscope studies revealed that the principal factor involved in the internalization was the degree of cell aggregation attained. Internalization occurred mainly by an endocytosis-like mechanism and took place during the elimination of PEG. The optimum conditions were to treat a mixed pellet of both microorganisms with 15% PEG and then gradually dilute the polymer. The same conditions were applied to E. coli and Aspergillus nidulans, with similar results. PMID- 1854205 TI - Comparative study of commercial 4-methylumbelliferyl-beta-D-glucuronide preparations with the Standard Methods membrane filtration fecal coliform test for the detection of Escherichia coli in water samples. AB - The performance capabilities of two commercial 4-methylumbelliferyl-beta-D glucuronide preparations were evaluated for the detection of Escherichia coli from water samples. Eighty-three water samples were collected from a treated water reservoir, and 32 samples were collected from untreated surface water. There was a statistically significant difference between the two commercial preparations compared with the Standard Methods membrane filtration fecal coliform (MFC) method for the detection of E. coli from treated water samples. However, there was no difference between the two methods and the MFC test for E. coli detection from the untreated surface water samples. The disagreement between the two commercial products and the MFC method was primarily due to the occurrence of false-negative results with the two commercial products. The data indicate that the occurrence of false-negative samples could be attributed to impaired substrate specificity and sensitivity of the two tests for E. coli detection. There was no apparent relationship between the occurrence of false negative results and heterotrophic plate counts in samples. PMID- 1854206 TI - Total coliform detection in drinking water: comparison of membrane filtration with Colilert and Coliquik. AB - The Colilert (CL) and Coliquik (CQ) systems were compared in a presence-absence format against the Standard Methods membrane filtration (MF) technique to determine whether differences existed in total coliform detection. Approximately 750 water samples were collected from distribution systems, covered and uncovered storage reservoirs, well sites, and the influent to drinking water treatment plants. Samples were analyzed for total coliforms and heterotrophic bacteria with MF, CL, and CQ. The agreements between CL and MF and between CQ and MF were both greater than 94.8%, which indicates that both may be acceptable methods for total coliform detection. Disagreement between the CL and CQ methods was primarily due to false-negative results. Furthermore, laboratory and field inoculation methods were compared for CL, more than 98% agreement was obtained. This finding indicates that sampling and immediate field inoculation may be an alternative to the traditional laboratory inoculation. PMID- 1854207 TI - alpha-Amylase of Clostridium thermosulfurogenes EM1: nucleotide sequence of the gene, processing of the enzyme, and comparison of other alpha-amylases. AB - The nucleotide sequence of the alpha-amylase gene (amyA) from Clostridium thermosulfurogenes EM1 cloned in Escherichia coli was determined. The reading frame of the gene consisted of 2,121 bp. Comparison of the DNA sequence data with the amino acid sequence of the N terminus of the purified secreted protein of C. thermosulfurogenes EM1 suggested that the alpha-amylase is translated from mRNA as a secretory precursor with a signal peptide of 27 amino acid residues. The deduced amino acid sequence of the mature alpha-amylase contained 679 residues, resulting in a protein with a molecular mass of 75,112 Da. In E. coli the enzyme was transported to the periplasmic space and the signal peptide was cleaved at exactly the same site between two alanine residues. Comparison of the amino acid sequence of the C. thermosulfurogenes EM1 alpha-amylase with those from other bacterial and eucaryotic alpha-amylases showed several homologous regions, probably in the enzymatically functioning regions. The tentative Ca(2+)-binding site (consensus region I) of this Ca(2+)-independent enzyme showed only limited homology. The deduced amino acid sequence of a second obviously truncated open reading frame showed significant homology to the malG gene product of E. coli. Comparison of the alpha-amylase gene region of C. thermosulfurogenes EM1 (DSM3896) with the beta-amylase gene region of C. thermosulfurogenes (ATCC 33743) indicated that both genes have been exchanged with each other at identical sites in the chromosomes of these strains. PMID- 1854208 TI - Immunofluorescence and morphology of Giardia lamblia cysts exposed to chlorine. AB - Giardia cyst-like objects detected by immunofluorescence in chlorinated water samples often cannot be positively identified by their morphological appearance. To determine the effect of chlorine on cyst immunofluorescence and morphology, Giardia lamblia cysts were exposed to chlorine for 48 h. The majority of cysts exposed to chlorine concentrations of 1 to 11 mg/liter at 5 and 15 degrees C lost their internal morphological characteristics necessary for identification, but most of them were still detectable by immunofluorescence. PMID- 1854209 TI - [Changes in future prospect in the management of breast cancer with special reference to BHENO- and GENO-type typic expression]. PMID- 1854210 TI - [Present status of computer utilization in cancer clinical trials]. AB - The present status of computer utilization in cancer clinical trials as regards trial planning, data management, statistical analysis and dissemination of knowledge is reviewed and some proposals for designing a new system are presented. In Japan, the importance of a statistical center for collaborative clinical trials has come to be recognized and interdisciplinary discussion on computer information system is just beginning. PMID- 1854211 TI - [Data input management in clinical trial]. AB - Data management in the clinical trial is not always processed adequately in Japan. Data management largely depends on the doctor who is in charge of the study. For the effective data processing to the computer, careful attentions should be paid to the proper selection of data-items and quantity, design of data format, coding of data to the format, and the procedure of data input into the computer. These procedures are mainly owed to data managers and computer engineers in the large clinical trials of western countries. Establishing local and central data center and identify of the data manager in our country are urgent for effective implementation of multiinstitutional clinical trial. PMID- 1854212 TI - [Cost of leukemia treatment]. AB - Medical cost has increasingly become an important problem in the medical practice. As one of the useful fields of computer in the hospital, we have analyzed the costs of chemotherapy and bone marrow transplantation in patients with leukemia who were diagnosed between 1983 and 1986 and followed up till Dec. 1989. For CML the difference in the cost was 5 million yen and a survival rate was 75% and was higher in BMT than in chemotherapy. For Acute leukemia the difference of the costs was 8 million yen and survival rates were 89% and 30%. These data may show that BMT is a very effective and economical treatment for leukemia. In this study we have analyzed only the direct medical cost paid by the governmental insurance, however there seems necessary many other costs which are not covered by the insurance such as the cost for the family members, the cost for cryopreservation of cells and sterilization tentatively covered by the hospital or the cost of blood or marrow bank which are covered or should be covered by the government. Evaluation of the treatment outcome by the parameters such as length and quality of life, productivity of the patient, prevention of the loss of social investment including education on the patient, seemed also necessary for justification of the medical cost. PMID- 1854213 TI - [Predictability of preclinical evaluation of anticancer drugs by human gastrointestinal cancer--nude mouse panel]. AB - We evaluated the predictability to clinical response of experimental effects of various anticancer agents on human cancer--nude mouse panel established in our department. The human cancer lines used were 12 gastric, 4 colorectal, 3 breast, 2 pancreatic cancers and 1 melanoma xenografted into BALB/c athymic nude mice under SPF conditions. Seven mice each with equivalent mean volume of sc inoculated tumor (about 100 mm3) were subjected to the treatment and control groups. Experimental treatment was conducted daily 25 times for antimetabolites, and intermittently 5 times once or twice a week for other drugs. Dosage of each drug adopted was maximal tolerated dose predetermined for the treatment schedule. Four weeks after the initiation of treatment, the therapeutic effect of each experiment was evaluated by the tumor growth inhibition rate (IR) based on the comparison of mean tumor weight between the 2 groups. When the IR was greater than 58%, the drug was evaluated as effective. The clinical response rate of each drug was referred from the result of the phase II study. Direct comparison of effects on 16 experimental chemotherapies in xenografts with responses to the corresponding clinical therapy of each donor patient revealed a fairly high accordance rate (94%). To elucidate the value of human cancer--nude mouse panel as the preclinical secondary screening, the response rates of 8 anticancer drugs treated to 15 cancer xenografts were compared with the cumulative clinical data available in each drug. Generally, the response rates of the human cancer xenografts to the drugs showed fairly good correlations with the cumulative clinical response rates of the corresponding drugs to the same organs. Using this panel, preclinical examinations of 6 new agents under development, including 254 S and other 2 CDDP derivatives, were performed in expectation the positive correlation with further clinical data. PMID- 1854214 TI - [Preclinical screening of chemotherapeutic and endocrine agents using human tumor xenografts--nude mouse system]. AB - Although newly developed antitumor agents had been screened using cultured human cell lines and rodent tumor systems, it was apparent that the positive antitumor activity of the agents on these experimental tumors is not a sufficient but a necessary condition to elucidate the antitumor activity on clinical human cancers. We have clarified that the chemosensitivity of human gastric, breast colon carcinoma xenografts could reproduce the essentially identical chemosensitivity of clinical carcinomas when the maximum tolerable doses of the conventionally available agents were administered to tumor bearing nude mice, and human breast carcinoma xenografts had a similar estrogen dependency and endocrine sensitivity to clinical human breast cancer. These findings indicated that the human tumor xenografts--nude mouse is an appropriate model to predict the clinical antitumor activity of newly developed antitumor agents. PMID- 1854215 TI - [Cancer therapy and nude mice]. PMID- 1854216 TI - [Drug sensitivity panel of human cancers transplanted in nude mice]. AB - Drug sensitivities of 76 human tumor lines/nude mice to 9 anti-cancer drugs were tested. Human tumor lines include pancreas cancers, brain tumors, neuroblastomas and etc. Tested anti-cancer drugs include MMC, 5-FU, and etc. When clinically equivalent dose of anti-cancer drugs were administered, drug sensitivities of these carcinomas were well correlated with clinical one, although blood brain barrier must be considered when brain tumors were tested. Our drug sensitivity panel revealed that cancers originated from the same organ showed the same tendency of drug sensitivity. Therefore, our drug sensitivity panel is thought to be useful to know the anti-cancer spectrum of newly developed anti-cancer drugs. Our panel is also useful to study the chemotherapy of rare cancers, because clinical studies of rare cancers are difficult. Expression of P-glycoprotein is correlated with drug resistance when treated with CED, but is not correlated with those when treated with MTD (maximum tolerate dose). That is human tumor lines with P-glycoprotein detected by C219 monoclonal antibody showed resistance to ADR, VCR and VLB when treated by CED, but the relationship was not observed when treated with MTD. PMID- 1854217 TI - [Preclinical trials from the standpoint of clinical trials]. AB - The establishment of reliable preclinical test is essential for the reasonable clinical trial. As a methodology for the screening of new active anticancer agents, disease oriented strategy using human tumor cell lines has been proposed in USA. The important questions in DOS are to determine the representative cell lines of specific cancer and it is also extremely important to decide the numbers of cell lines used for the screening. CPT-11, topoisomerase I inhibitor, developed in my country has been demonstrated to be active against lung cancer cell lines compared with mice tumors such as S-180 and P-388. However, no compound is demonstrated to be clinically active so far by this methodology. The criteria for the application of clinical trial are obscure and each drug company decides empirically by themselves. We have proposed to use PEI (predictive efficacy index) for the prediction of antitumor activity of new compounds. The clinical effect of new platinum analogue well correlated with this value. We have conducted phase II trial of 5-FU + LV against NSCLC without no prior chemotherapy. No responder was observed in the trial. Augmentive effect of leucovorin on the cytotoxicity of 5-FU and FdUrd was examined in vitro against NSCLC and colon cancer cell lines. Leucovorin stimulated the cytotoxicity of both drugs only against colon cancer cell lines. We tried to predict the response rate of new platinum derivative based on the data of bioassay of patient's serum administrated with platinum compounds. The predicted response rates of 254-S were 57-67% and 16-27% against SCLC and NSCLC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854218 TI - [Phase I trials--clinical studies of antineoplastic agents]. AB - The establishment of the starting dose and the dose escalation are the principal issues of the Phase I trials of anticancer agents. We report the procedures and results of the Phase I studies we participated in Japan in the 1980's concerning 17 intravenous anticancer agents. The drugs indicated a correlation between the mouse LD10 and the man MTD (maximum tolerated dose) in mg/m2. Median mouse LD10 (135 mg/m2) approximated to median man MTD (137 mg/m2) in mg/m2. One fifth of the mouse LD10 was lower than the man MTD. Therefore, as recognized at the 23rd Annual Congress, Japan Society for Cancer Therapy, the lower one of either 1/5 the mouse LD10 or 1/3 the dog TDL (toxic dose low) in mg/m2 has to be determined as safe starting dose. The modified Fibonacci search scheme has been generally adopted for the dose escalation. 14 applicable drugs were examined including 7 drugs in the early 1980's and 7 drugs in the late 1980's. The real number of steps that reached the man MTD was compared to the number of the steps taken in the dose escalation by the Fibonacci's method. The real steps were more than the Fibonacci's ones in the late 1980's. It showed the tendency of a more careful and safer dose escalation, however, to put it critically, the dose escalation was not efficient enough. It is expected that the contradictory problem between safety and efficacy in the Phase I studies will be solved by developing methods like pharmacokinetic study in animals and man. PMID- 1854219 TI - [Phase I clinical study of antineoplastic agents]. AB - Routinely, phase I clinical study starts with 1/10 of MELD10, provided dog does not produce toxicity. This is empirical method depend upon previous agents. In these days, many new agents appear to clinical study and some of them require so many steps to reach MTD. This is mainly depends upon differences of ADME between animals and human, which is possible to eliminate by pharmacokinetic studies. On the other hand, some of agents exceed MTD with initial dose of 1/10 MECL10. This is mainly due to difference of target organ sensitivity, and could be eliminated by assay of tissue enzyme activities. Another point should be emphasized is the existence of plasma peak level toxicity. This should be eliminated to perform preclinical study of LD10 by continuous infusion rather than iv bolus injection. Since some of new agents have DLF of neuro, hepato or cardiac toxicity rather than bone marrow, those would show quite different behaviors, therefore a special attention should be given for further studies. PMID- 1854220 TI - [Phase II clinical trial of anticancer drugs]. AB - For the evaluation of the therapeutic efficacy of anticancer drugs, we should perform the clinical trials step by step under the protocol with well designed and considered the ethical aspects. In the phase II study, it should determine whether a drug has antitumor activity. In our country, many investigators used the criteria of the Japan society for cancer therapy and also used the criteria made by every society of medical department. It should have a formal registration mechanism for entry. And all patients including the ineligible and incomplete cases (withdrawal and dropouts) should be reported. This is particularly important in the assessment of response rate, because response rate is directly influenced by the numbers of ineligible and incomplete cases. The efficacy is effected by the various prognostic factor and it is necessary to arrange the patients with uniform prognostic factor. The adequate sample size also should be required enough to establish the efficacy of the antitumor activity. PMID- 1854222 TI - [Extraordinary symbiosis: skeletal muscle and non-repairable myocardium]. PMID- 1854221 TI - [Problems of clinical trials as viewed in the perspective of decision theory]. AB - In this paper, the current clinical trial based on the Neyman-Pearson's principle of hypothesis testing is reviewed in the perspective of decision theory, its shortcomings are revealed and alternative methods proposed. In the current trial design, the alpha error is arbitrarily fixed at a level (e.g., 0.05), even lower than the beta error level (0.1 or 0.2). This results in failure with smaller trial size to identify the better treatment, dose-patient interaction, or optimal patient stratum for treatment. If on the other hand, the most harmless alpha error is ignored, the total number of patients expected to be cured can be substantially increased due to earlier identification of the better treatment. In case treatment, A has some disadvantages compared with B in terms of cost, toxicity etc., then the null hypothesis should be changed to "the cure rate of A is greater than that of B by delta", an adjustment for the disadvantages, which can be estimated by utility analysis. The loss to the society and target population may be further increased if improper regimen is provided including omission of the best treatment arm, suboptimal treatment intensity, selection of improper patient stratum, failure to individualize treatment plan (inflexible regimen). In order to maximize the benefit of our patients and society, radical changes of the current clinical trial design is needed using decision analytical approach. PMID- 1854223 TI - [Doppler color transesophageal echocardiography. Report of the first 110 studies carried out at the Ignacio Chavez National Institute of Cardiology]. AB - Transesophageal echocardiography allows views of the posterior structures of the heart. This approach provides additional and complementary information to the transthoracic study, it is also an alternative in those patients with technical limitations for optimal precordial imaging. This study analysis the first 110 cases studied with transesophageal echocardiography in the National Institute of Cardiology Ignacio Chavez. They correspond to patients with valvular heart disease, prosthesis, acute and chronic ischemic heart disease, dissecting aortic aneurysm, cardiomyopathies, thrombus, tumors and masses. As well as paediatric and adult with complex congenital heart disease. The advantages of the transesophageal technique compared with the precordial approach are described. PMID- 1854224 TI - [Comparative study of 2 mechanical mitral valves]. AB - We present the long term follow-up of two groups of patients under 16 years of age in whom two different types of mitral valve prostheses were used for the treatment of mitral valve disease. Group I was formed by 74 patients with Starr Edwards (6120) prosthesis and group II by 36 cases with Bjork-Shiley prosthesis. Group I was followed for a mean period of 11 years and group II for a mean period of 7.5 years. The clinical evolution of both groups assessed according to the New York Heart Association criteria showed improvement of the functional class (p less than 0.006). Twenty seven cases of group I and 21 of group II underwent cardiac catheterization for the evaluation of surgical results. In group I, the mean pulmonary arterial systolic pressure (PASP) decreased from 57 mmHg to 33 mmHg (p less than 0.001) and the mean pulmonary arterial wedge pressure (PAWP) from 20.8 mmHg to 12.1 mmHg (p less than 0.05). In group II, the mean PASP decreased from 59.2 mmHg to 28.5 mmHg (p less than 0.001) and the mean PAWP from 24.6 mmHg to 8.5 mmHg (p less than 0.001). There was statistically significant difference for a greater incidence of thromboembolism in group I (p = 0.037). No differences were found for bacterial endocarditis, dysfunction and death. PMID- 1854225 TI - [Mitral valve insufficiency in acute myocardial infarction. Assessment with pulsed and coded Doppler color]. AB - We studied 108 patients who sustained an acute myocardial infarction (AMI) by means of echocardiography, pulsed doppler (PD) and Doppler color flow imaging (CD). We evaluate the presence of mitral regurgitation (MR) and it relationship to the site of the AMI and also to the ventricular function. The incidence of MR was 50.92%, (55/108), it was detected in higher percentage when the AMI was inferior (61.8%) than when anterior (39.6%). The correlation with the ejection fraction (EF) was only significative when the AMI was anterior. The incidence of MR was 57.1% when the EF was below 25%. CD had better diagnostic capabilities independently of the site of the AMI, (48% vs 32.1% when the AMI was anterior and 76.1% vs 52.6% when it was inferior). PMID- 1854226 TI - [Balloon catheter valvuloplasty for calcified aortic stenosis in adults. Report of a case and review of the literature]. AB - The first procedure of balloon valvuloplasty in adult calcific aortic stenosis was performed in Mexico on July 17 of 1987. It was a 69 year old female with calcific aortic stenosis and unstable, progressive angina pectoris. Cardiac catheterization showed trans-aortic gradient of 90 mmHg, minimal aortic regurgitation and ejection fraction of 85 percent. Aortic valvuloplasty was performed immediately after cardiac catheterization using the arterial retrograde way by means of a 15 mm. in diameter catheter initially and another of 18 mm. in diameter afterwards. At the end of procedure the gradient diminished to 56 mmHg and an slight increase of the aortic insufficiency was observed. The Doppler echocardiogram showed decreased severity of the stenosis. The patient was discharged asymptomatic and continued to do well for six months. She died suddenly after that period of time. A review of the literature is also presented. PMID- 1854227 TI - [Correlation of the transaortic gradient determined with doppler echocardiography versus catheterization in patients with aortic stenosis]. AB - The purpose of this report is to evaluate the reliability of a non-invasive estimation of a transaortic gradient in patients with valvular aortic stenosis by doppler echocardiography. We compared the transvalvular gradients obtained by cardiac catheterization (invasive) versus the estimation by non-invasive technique such as continuous-wave doppler in 30 consecutive patients with valvular aortic stenosis. When compared the peak velocity (Vmax) of the aortic jet versus the gradient obtained by cardiac catheterization we found a correlation coefficient (r) of 0.83 and when compared the gradient obtained by both methods we found an r value of 0.85. These results show that the calculations of aortic gradient by echo-doppler, are reliable. Besides this method allowed us to establish the correct diagnosis and to follow up these patients. PMID- 1854228 TI - [Electrophysiologic effect of intravenous propafenone in supraventricular tachycardia]. AB - The electrophysiologic effects of intravenous propafenone were studied in twenty six patients with supraventricular tachycardias. Ten patients (38%) with intranodal reentrance tachycardia common type, and sixteen patients (62%) atrioventricular orthodromic reentrance tachycardia. Propafenone (2 mg/kg intravenously) given over ten minutes period caused termination of the intranodal reentrance tachycardia in 60% of the cases and 50% to the patients with atrioventricular reentrance tachycardia. The antiarrhythmic effects observed are related to the slowing of the conduction velocity and to the prolongation of the refractoriness in the AV node and accessory pathways preventing the reentrance mechanism. The reinduction of the tachycardia was possible in 46% of the patients. This effects was more significative in the group with accessory pathways (50%), and 40% of the patients with intranodal reentrance. The supraventricular tachycardia was inducible by programmed electrical stimulation in 46% of the patients. None of the patients developed side effects to the administration of the propafenone. PMID- 1854229 TI - [Rheumatic cardiopathy in children younger than 6 years of age]. AB - Most of the published papers on Rheumatic Fever (RF) have not included the younger population. We selected 211 cases of children with RF younger than 6 years of age from 9,471 clinical files from 1944 to 1982. These were followed retrospectively to identify the presence of rheumatic activity, subsequent attacks and penicillin profilaxis. From de 211 cases, 209 had carditis; 57% of them were girls and 43% boys. There were no previous infections of the upper respiratory tract in 36% of the patients. The number of cases with RF increased abruptly after 3 years of age and continued increasing until 5 years of age when 70.5% of the population had there first clinically recognized attack. Lesions were present in the mitral valve in 80% of the cases, in the aortic valve in 12%, in the tricuspid in 5% and in the pulmonary valve in 3%. The death rate during the first attack was 20% being refractory heart failure the main cause of death. Thirteen cases suffered rheumatic pneumonia, 9 of whom died (69.2%). CONCLUSIONS: 1) The incidence of acute rheumatic fever in children under 6 years of age has decreased with time. 2) The death rate as well as the valvular damage decreased with the parents cooperation with the treatment. 3) The changes in the clinical picture and the severity of valve sequelea may be due to penicillin profilaxis and the better understanding of the disease. PMID- 1854230 TI - [Primary anti-phospholipid syndrome. Clinical experience at the Ignacio Chavez National Institute of Cardiology]. AB - This paper describes 15 patients who had elevated IgG antibodies reactive with cardiolipin. Outstanding clinical features were: recurrent venous and/or arterial thrombosis--often extensive and severe--in 9 cases. Thrombocytopenia, in 11 cases and spontaneous recurrent fetal loss in 8 out of 10 females with marital life. In addition there were vasospastic/thrombotic features such as livedo reticularis, Raynaud's phenomenon and leg ulcers. Involvement of central and/or peripheral nervous system was present in 10 cases. Valvular heart disease was conspicuous, 10 out of 15 patients (66%) had organic lesions in both sides of the heart. There were also laboratory abnormalities such as prolonged partial thromboplastin time, false positive V.D.R.L., plasmatic anticoagulant activity and low incidence of antinuclear antibodies and rheumatoid factors. The clinical syndrome seems to be related to the presence of antibodies reactive with anionic phospholipids, although there is not formal proof of a direct cause effects relationship. Recognition of these distinct clinical entity is important, the use of simple anti aggregating agents like aspirine and careful anticoagulant therapy may modify the course of this newly recognized autoimmune condition. PMID- 1854231 TI - [Assessment of the ejection fraction of the right ventricle with echocardiography]. AB - The purpose of this article is to evaluate and compare the right ventricular ejection fraction (RVEF) as parameter of right ventricular function by means of echocardiography. We studied 16 patients (15 male, 1 female) from 48 to 82 years of age (mean 58 years) from whom 8 had history of myocardial infarction (MI) with extension to the right ventricle (RV) in a period of time no longer than 7 days. The MI was diagnosed clinically as well as by enzymes, electrocardiogram and cardiac gammagram with 99mTc-pyrophosphate. The other 8 patients were healthy subjects or patients with stable angina pectoris. In all patients a two dimensional echocardiogram was performed with and apical four and two chamber view according to Simpson's rule; a subcostal approach was performed for the area length method of Dodge. The values obtained of RVEF with each method were compared with those obtained by nuclear medicine. The apical views were obtained in 14 patients (87%) and the RV outflow tract was seen in 15 patients (93%). There were no significant statistical difference between the two methods. The highest correlation for RVEF respect to nuclear medicine was obtained with the area-length method with r = 0.85 and p less than 0.001 while for the Simpson method we obtained r = 0.79 and a p less than 0.001. We conclude that the determination of the RVEF is achievable in patients with MI of the RV and area length method is the most useful. PMID- 1854232 TI - [Current causes of mortality in acute myocardial infarction]. AB - The mortality rate of acute myocardial infarction (AMI) has decreased from 50% in 1926 to 9% nowadays. The reason for this change has been the development of coronary care units, the use of new inotropic agents, antiarrythmic drugs, pacemakers, as well as the better knowledge of the right ventricular infarction and heart failure. We studied 100 fatal AMI (group II) out of 1187 patients admitted to the Instituto Nacional de Cardiologia "Ignacio Chavez" CCU up to august 1987 and compared them with 500 survivors of acute coronary occlusion in the same period., (group I) - In both groups there were more men between 50 and 70 years. Females older than 60, had a higher mortality rate. Twenty patients died with clinical evidence of tamponade, five of them had left ventricular rupture at autopsy. The fatal AMI group had higher rates of past history of myocardial infarction, also higher rates of persistent angina, myocardial re infarction, 3er degree AV block and RBBB. The more frequent causes of death were grade III-IV heart failure and left ventricular wall rupture. PMID- 1854233 TI - [Long-term follow-up of the Hancock prostheses]. AB - Our purpose was to investigate the long term outcome of Hancock bioprostheses at our Hospital. There were 128 bioprostheses, with histopathological study on 17 of them. The 12.8 years follow-up disclosed dysfunction on 48.18% with an annual dysfunction rate of 3.34 +/- 1.3. One half of the patients with prosthetic dysfunction were re-operated. A comparison of our results is made with those of the literature, either with biological or mechanical prostheses. PMID- 1854234 TI - [Lipoprotein metabolism disorders. II. Epidemiology, classification, and diagnosis]. PMID- 1854235 TI - Tumor inhibiting [1,2-bis(difluorophenyl)ethylenediamine]dichloroplatinum (II) complexes, I: Synthesis. AB - The synthesis of the diastereomeric 1,2-bis(2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3,5 difluorophenyl)ethylenediamine (meso, D/L 8-13) from meso 1,2-bis(2 hydroxyphenyl)ethylenediamine and the respective difluorobenzaldehyde by a diaza Cope-rearrangement and their conversion into the [1,2-bis(2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3,5-difluorophenyl)ethylenediamine]dihaloplatinum(II)- complexes (meso, D/L 8-13 PtCl2; meso D/L 9- and 11-PtI2) with K2PtHal4 (Hal = Cl, I) is described. From the diiodoplatinum(II)-complexes (meso D/L 9- and 11-PtI2) the better water soluble diaqua[1,2-bis(2,4- and 2,6-difluorophenyl)ethylenediamine]platinum(II) sulfates (meso, D/L 9- and 11-PtSO4) are obtained by reaction with Ag2SO4. PMID- 1854236 TI - Analogues of biologically active compounds, IV: Synthesis of some 8 arylazoguanines. PMID- 1854237 TI - [Synthesis and cytostatic actions of 10- and 11-nitronoracronycins, molecular variations of cytostatically active acronycine]. AB - The syntheses of 11- and 10-nitronoracronycine (10 and 11) from 1,3-dihydroxy-10 methyl-5-nitroacridinone (7) or 1,3-dihydroxy-10-methyl-6-nitroacridinone (8), respectively, and 2-chloro-2-methyl-3-butyne are reported. In screening tests with the transplantation tumor leukemia P 388 10, 11, 7 and 1,3-dimethoxy-10 methyl-6-nitroacridinone showed cytotoxicity. 8 and 1,3-dimethoxy-10-methyl nitroacridinone (5) proved to be inactive. PMID- 1854238 TI - [Studies on the chemistry of O,N- and S,N-containing heterocylics. 10. Synthesis and biologic activity of 2-substituted 2-ethylbenzoxazoles]. AB - 2-Vinylbenzoxazole (3) is obtained by condensation of acrylic acid with 2 aminophenol in a mixture of phosphorus pentoxide/methansulfonic acid. Interaction of 3 with N-, O-, and C-nucleophiles yields 2-substituted 2-ethyl-benzoxazoles. Compounds 8a, 8b and 8e show analgetic activity in mice. Moreover, fungicide, insecticide and nematocide activity of some compounds is found. PMID- 1854239 TI - One of us. PMID- 1854240 TI - Surgical options in 424 patients with primary breast cancer without systemic metastases. AB - Mastectomy was dictated by medical considerations in about 40% of 424 consecutive patients who had invasive breast cancer with no evidence of systemic metastases. Half of the women considered suitable for local excision of the breast cancer followed by radiotherapy (conservation) elected to have mastectomy, and intraoperative findings dictated mastectomy in about 20% of those electing conservation. Consequently, conservation was accomplished in about one quarter of those treated for breast cancer. Younger rather than older women more frequently expressed the desire for breast conservation. PMID- 1854241 TI - The role of tagged red blood cell imaging in the localization of gastrointestinal bleeding. AB - The records of 162 patients who underwent technetium-99m-tagged red blood cell scans for the localization of gastrointestinal hemorrhage were studied. Ninety eight scans were read as positive, with bleeding sites determined by a radiologist. Forty-six patients had a definitive diagnosis made by other means. Tagged scans accurately localized the site of bleeding in only 52% of cases. Analysis of the value of these tagged scans in predicting a subsequent positive angiogram indicated that there were 14 positive and 12 negative angiograms of 26 positive scans. Of the nine patients with negative scans who underwent arteriography, the arteriogram was positive in five. These data suggest that tagged red blood cell scanning is a poor diagnostic technique for the localization of gastrointestinal bleeding, and its use as a screening tool before angiography is questionable. PMID- 1854242 TI - Extracorporeal lithotripsy. An important adjunct in the nonoperative management of retained or recurrent bile duct stones. AB - Retained or recurrent bile duct stones can be successfully removed in up to 80% to 85% of patients with the use of percutaneous or endoscopic techniques. However, problems related to difficult biliary access, large stones, and biliary strictures may decrease the success rate of this approach. We evaluated the safety and efficacy of extracorporeal shock-wave lithotripsy (ESWL) in 16 patients with complicated biliary stones treated prospectively over a 24-month period. Successful stone fragmentation was achieved in 15 patients (94%) using a Dornier HM3 lithotripter (average of 2290 shocks at 22 kV). Three patients (19%) required a second ESWL treatment. Biliary clearance of stone fragments was spontaneous in seven (43%) of the patients and required additional treatment in eight (57%) of the patients. Complications from ESWL were minor and included transient hematuria and ecchymoses at the skin entry site. Extracorporeal shock wave lithotripsy failed in one patient (6%) with a biliary stricture and surgery was required. At hospital discharge, all patients were asymptomatic and stone free. Treatment with ESWL appears to be a safe and effective adjunct for selected patients with complex biliary stone disease. PMID- 1854243 TI - Biliary pancreatitis. Operative outcome with a selective approach. AB - To evaluate the efficacy of a selective approach to biliary pancreatitis, we reviewed the outcomes in 276 consecutive patients undergoing operations for this diagnosis during a 7-year period. Initial conservative therapy resulted in elective operations in 63% and urgent operations in 37%. Only 10 patients (3.6%) required primary pancreatic operations, 50% of them as emergencies. The proportion of common duct surgical explorations fell from 70% of those operated immediately after hospital admission to 20% by the third hospital day. Overall mortality was 1.8% but was increased to 30% in patients having an initial pancreatic operation. We conclude that a selective approach to biliary pancreatitis allows the operation to be performed electively in most patients and is associated with a low mortality and an acceptable length of stay. Most common duct stones pass spontaneously permitting cholecystectomy alone. PMID- 1854244 TI - Surgical evaluation of Henoch-Schonlein purpura. Experience with 110 children. AB - Henoch-Schonlein purpura is a disorder of unknown origin that is probably related to an autoimmune phenomenon. This report concerns 110 children (mean age, 6.2 years; range, 6 months to 14 years) with Henoch-Schonlein purpura. Seventy-two (65%) had abdominal pain associated with nausea and vomiting, bloody stool, and upper gastrointestinal bleeding. Sixty patients with abdominal pain were evaluated and treated conservatively. However, 12 patients underwent laparotomy. Six underwent unnecessary appendectomy for wrongly diagnosed appendicitis. Bowel resection was performed in one patient for an obstructive ileal lesion. Six additional patients had intussusception; surgery was required in three, while barium enema reduction was successfully accomplished in three others. Massive gastric hemorrhage required ligation, vagotomy, and pyloroplasty in two instances. One child with severe scrotal pain, hemorrhage, and swelling underwent unnecessary scrotal exploration. Four additional patients with similar symptoms avoided operation after a testicular scintiscan demonstrated good blood flow. A high index of suspicion and early diagnosis of Henoch-Schonlein purpura based on clinical, roentgenographic, and laboratory findings may avoid unnecessary operations in most cases. However, life-threatening complications (hemorrhage, obstruction, and intussusception) may occur and require operative intervention. All of the patients survived. PMID- 1854245 TI - Acute diverticulitis. A complicated problem in the immunocompromised patient. AB - We reviewed the records of 209 patients with acute diverticulitis treated from 1984 through 1989 to determine if immunocompromised patients have a worse prognosis than nonimmunocompromised patients. Forty immunocompromised patients and 169 nonimmunocompromised patients with acute diverticulitis were identified. Free perforation into the peritoneal cavity occurred in 43% (17/40) of immunocompromised patients and 14% (24/169) of nonimmunocompromised patients. Operations were performed in 58% (23/40) of immunocompromised patients and 33% (55/169) of nonimmunocompromised patients. Postoperative morbidity was 65% (15/23) in immunocompromised patients and 24% (13/55) in nonimmunocompromised patients; postoperative mortality was 39% (9/23) and 2% (1/55), respectively. We conclude that acute diverticulitis in the immunocompromised patient is a complicated problem; there is a greater risk of free perforation and need for surgery than in the nonimmunocompromised patient. Furthermore, the prognosis for immunocompromised patients who undergo surgery is worse than that for nonimmunocompromised patients. PMID- 1854246 TI - A growing spectrum of surgical disease in patients with human immunodeficiency virus/acquired immunodeficiency syndrome. Experience with 120 major cases. AB - One hundred twenty major general surgical procedures were performed on 88 adult patients harboring the human immunodeficiency virus. Fifty-eight (48%) of the procedures were performed on patients who fulfilled the criteria for acquired immunodeficiency syndrome. The patients were predominantly male (94%). Single risk factors included homosexuality (73% of cases), intravenous drug abuse (8%), and previous blood transfusions (8%). Four patients (5%) had multiple risk factors; risk factors were denied by seven patients (8%). The mean age at surgery was 41.6 years (range, 22 to 67 years). Surgical conditions that rarely affect the population without the human immunodeficiency virus presented diagnostic challenges. Altered physiologic responses to even routine conditions were observed. Thirty-day morbidity rates for emergency (group A) and elective (group B) procedures were 19% and 9%, respectively. This included seven surgical deaths (13%) in group A and one in group B (2%). Patients undergoing 92 of 112 procedures (82%) not associated with surgical mortality were followed up. Patients who were dead at follow-up had mean procedure-survivals of 19 weeks (group A) and 21 weeks (group B) for 33 procedures. Those who remained alive had a mean procedure-survival of 86 weeks for 59 procedures. No single prognosticator could be correlated with outcome, although the combination of hypoalbuminemia with a history of opportunistic infection(s) was associated with short survival. Emergency and elective procedures can be performed in the patient with human immunodeficiency virus/acquired immunodeficiency syndrome with acceptable morbidity and mortality. Procedures are indicated to extend patient life or to improve quality of life. PMID- 1854247 TI - Management of infected aortoiliac aneurysms. AB - A 30-year retrospective review identified 13 patients treated for infected aneurysms of the abdominal aorta or iliac arteries, for an overall incidence of 0.65%. A constellation of clinical findings led to the correct preoperative diagnosis in 11 (85%) of 13 patients. Treatment methods included resection and in situ replacement grafting in seven patients, resection and extra-anatomic bypass in five patients, and resection-ligation in one patient. Four (31%) of 13 patients died within 30 days of operation, three of whom died of rupture. Overall, good results were achieved in five patients (38%), while poor results were noted in the remaining eight patients (62%). The determinants of outcome were aneurysm location or rupture, the presence of established infection, and the virulence of the infecting organism. In 10 (77%) of the 13 aneurysms, Salmonella species, Bacteroides fragilis, Staphylococcus aureus, and Pseudomonas aeruginosa accounted for all deaths, ruptures, and suprarenal aneurysm infections. These data suggest that patients with primary infections of the abdominal aorta or iliac arteries continue to present with advanced infections or aneurysm rupture that result in a high mortality. PMID- 1854248 TI - Dipyridamole thallium scanning in the evaluation of coronary artery disease in elective abdominal aortic surgery. AB - Dipyridamole thallium scanning was routinely performed on 68 consecutive patients who presented for elective aortic surgery. All 68 patients were judged by clinical assessment to be at low risk for perioperative cardiac complications. In addition, 42 of 68 patients had a history of myocardial infarction, stable angina, or abnormal echocardiographic findings (group 1). Twenty-six of 68 patients did not have a history of myocardial infarction, angina, or abnormal echocardiographic findings (group 2). In group 1, 34 of 4 patients had positive results on dipyridamole thallium scanning, and 15 of these patients were found to have critical coronary artery disease on subsequent cardiac catheterization; nine underwent immediate coronary artery bypass grafting, and six had their coronary artery disease treated medically and their vascular operations cancelled. The remaining 27 patients in group 1 underwent elective operations, with six (22%) of 27 sustaining postoperative cardiac complications. None of the group 2 patients was found to have critical coronary artery disease. All patients in group 2 underwent aortic operation without cardiac complication. Routine dipyridamole thallium scanning detected a 22% (15 of 68) incidence of critical coronary artery disease overall. There was a 36% (15 of 42) incidence of critical coronary artery disease in group 1 patients vs 0% in group 2 patients (95% confidence interval, 21% to 50%). We conclude that the use of dipyridamole thallium scanning in low risk patients for cardiac screening prior to elective aortic operations is beneficial in selected patients who have a history of myocardial infarction, angina, or abnormal echocardiographic findings, but is not necessary in patients with no history of coronary artery disease. PMID- 1854249 TI - Concomitant benefit of preoperative irradiation in preventing pancreas fistula formation after pancreatoduodenectomy. AB - Preoperative irradiation improves both the resectability and curability of carcinoma of the pancreas head area and should improve patient survival. We retrospectively investigated the value of preoperative irradiation in preventing pancreatic fistula formation. Of 76 consecutive patients who underwent pancreaticojejunostomy by mucosa-to-mucosa anastomosis with a stent catheter after pancreatoduodenectomy, 22 had received preoperative irradiation. The irradiation field included the anastomotic site. In two patients, accidental dislocation of the stent catheter was the apparent cause of fistula formation, but the other 21 patients in the irradiated group developed no fistula. In contrast, nine (17%) of 53 patients in the nonirradiated group developed fistulas. In the irradiated group, preoperative selenomethionine Se 75 scintigraphy revealed a cold area corresponding to the pancreas body, which was included in the irradiation field. Thus, a putative decrease in exocrine function at the pancreatic anastomotic site could explain why fistula formation was prevented by preoperative irradiation. PMID- 1854250 TI - Pharmacokinetics of cefazolin applied topically to the surgical wound. AB - Topical application of antibiotics is used in the prophylaxis of postoperative surgical infections. However, whether topically applied antibiotics remain primarily in the surgical wound fluid or are systemically absorbed is uncertain. The pharmacokinetics of topically applied cefazolin were studied in a canine model that allowed simultaneous determination of serum and wound fluid antibiotic concentrations. Topical administration of cefazolin resulted in high antibiotic concentrations in the wound fluid for prolonged periods and rapid systemic absorption. Bioavailability after topical administration was 95%. Within 1 hour, the serum concentrations after topical administration equaled the serum concentrations after intravenous administration, and the concentration time curves declined in parallel. In wound fluid, the mean time above the susceptibility break point minimum inhibitory concentration after topical administration of cefazolin was 5.76 hours compared with the estimated time above the minimum inhibitory concentration of 2.55 hours after intravenous administration. PMID- 1854251 TI - Bleeding peptic ulcer after abdominal aortic aneurysm surgery. AB - A retrospective study of 112 patients with abdominal aortic aneurysm (AAA) and 232 with arteriosclerosis obliterans (ASO) demonstrated that 16.7% of those with AAA and 1.6% of those with ASO had a history of gastroduodenal ulcer; 83% of these lesions with AAA were gastric ulcers. Ulcer bleeding after vascular reconstruction developed in seven patients with AAA and one with ASO. Serum fibrinogen levels and platelet counts were significantly lower in patients with AAA than in those with ASO or controls. A prospective study showed that 25 (52.1%) of 48 patients with AAA and six (20.0%) of 30 patients with ASO had endoscopically proved gastroduodenal lesions before vascular reconstruction. None of them developed postoperative bleeding after treatment of both their gastroduodenal lesions and coagulopathy. Furthermore, the significant decrease in blood flow and prostaglandin content of gastric mucosa was demonstrated in patients with AAA. PMID- 1854252 TI - Randomized study of interleukin 2 (IL-2) alone vs IL-2 plus lymphokine-activated killer cells for treatment of melanoma and renal cell cancer. AB - The purpose of this study was to evaluate the efficacy and safety of a continuous infusion interleukin 2 (IL-2) regimen for patients with metastatic melanoma and renal cell cancer. To investigate the contribution of adoptively transferred lymphokine-activated killer cells, patients were randomized to receive either IL 2 alone or IL-2 plus lymphokine-activated killer cells. Twenty-three patients with renal cell carcinoma and 20 with melanoma were entered into the protocol. There were no objective responses noted in the 38 assessable patients (20 with renal cell carcinoma, 18 with melanoma). Most patients demonstrated progressive disease following one 31-day cycle of weekly continuous-infusion IL-2. Grade I and II toxic reactions, including fever, rash, anorexia, and weight gain, were common and treated symptomatically. Significant in vivo stimulation of lymphokine activated killer and natural killer cell activity was noted in most patients. This continuous-infusion IL-2 regimen with or without lymphokine-activated killer cells was ineffective in the treatment of melanoma and renal cell carcinoma. PMID- 1854253 TI - Inflammatory pseudotumors of the spleen. AB - Inflammatory pseudotumors are uncommon benign lesions that have been found in numerous organ systems. However, their appearance within the spleen is decidedly rare. Grossly, pseudotumors appear as well-circumscribed, encapsulated masses, while microscopic examination reveals a polymorphous inflammatory cell infiltrate occurring variably with granulomatous reaction, fibrosis, and cell necrosis. Because they often present either as unexplained, asymptomatic masses or with vague constitutional symptoms, splenic inflammatory pseudotumors can raise suspicion for a primary splenic neoplasm, such as lymphoma. Splenectomy is the treatment of choice. PMID- 1854254 TI - [Investigation of the genetics in allergic children: the first report--Twin study on HLA in allergic disease]. AB - Twenty-two twins' families were investigated to determine the influence of a genetic factor in the etiology of allergic diseases in children. Zygosity was confirmed by eight red cell blood types and HLA type. Eight pairs of monozygotic twins were divided by a probability of monozygosity as calculated from Essen Moller's method. Concordance rate of allergic disease and asthma were 88% in MZ, 86% in DZ, 75%, 73% and that of positive rate of DF-specific IgE antibody were 60% in MZ, 58% in DZ. In DZ, not sharing the same HLA haplotypes, concordance of the positive rate of DF-specific IgE antibody was 0%. Concomitant coefficiency of total serum IgE levels were 0.593 in MZ, 0.063 in DZ. These data suggested that IgE production may be influenced by genetic factors. PMID- 1854255 TI - [Kinetics of the falling of airborne mite allergens (Der I and Der II)]. AB - A futon (Japanese quilt) was beaten to disperse mite allergens into the air in a closed room, and the airborne allergens were collected both by Andersen air sampler for particle size analysis and by slit air sampler for kinetic analysis of the clearing of the allergens from the air. After extraction of the allergens from the agar plates in the samplers, two kinds of major mite allergens (Der I and Der II) were immunochemically quantitated. We found that the aerodynamic diameters of both allergens were mainly above 5.5 microns, and that airborne allergen levels decreased to about 10% of the starting level in 30 minutes, indicating the rapidity of the falling of both allergens. PMID- 1854256 TI - [Evaluation of different treatments of Japanese bed quilts for reducing mite allergens]. AB - We evaluated the effectiveness of different treatments of Japanese bedquilt (futon) in reducing mite allergens: vacuum-cleaning, beating plus vacuum-cleaning and washing of the whole futon in water. Before and after these treatments, small amounts of cotton were taken out of the futon and mite allergens were extracted from the cotton into water. The absolute contents of two kinds of major allergens of two Dermatophagoides species were immunochemically quantitated. We found that beating and vacuum-cleaning reduced the allergen contents by only about 40%, whereas washing reduced the allergens by more than 90%. Therefore, for reducing airborne mite allergens generated from futon, we think that washing the whole futon in water is the most effective method. PMID- 1854257 TI - [Usefulness of AlaSTAT, a new method for the measurement of IgE]. AB - AlaSTAT is an enzyme-immunoassay method for the measurement of allergen specific IgE antibodies. This method has a special feature in that carbohydrate, nucleic acid and fat as well as protein allergens can be used as antigens. In this study, IgE antibodies were measured by the use of AlaSTAT kits which were able to detect IgE antibodies to protein or nucleic acid allergens, and the results were compared to those of skin tests and RAST. 1367 samples from 479 patients were examined with 20 allergens. The capacity in the AlaSTAT system was larger than that in the RAST system. The correlation coefficient between AlaSTAT and RAST was 0.90 (p less than 0.01) and the correspondence rate was 90.7%. When the rice allergen was used in RAST, a nonspecific reaction was observed at high concentrations of total IgE. However, no such reaction was observed in AlaSTAT, even with total IgE of 10,000 IU/ml. The sensitivity, specificity and correspondence rate to skin tests was 71%, 87% and 75% respectively. The specificity of AlaSTAT seemed to be slightly higher than that of RAST, but the sensitivity and the correspondence rate were similar to those of RAST. From these results, AlaSTAT appears to be a good or better method for the measurement of IgE antibodies in comparison with RAST. PMID- 1854258 TI - [The role of 5-lipoxygenase products in the development of airway responsiveness induced by platelet activating factor inhalation in dogs]. AB - To determine whether 5-lipoxygenase products are involved in the development of airway responsiveness and in the infiltration of inflammatory cells into the airway after platelet activating factor (PAF) inhalation, we studied the effect of a selective 5-lipoxygenase inhibitor, AA-861 on PAF-induced airway hyperresponsiveness and on the increase of neutrophil and eosinophil counts in bronchoalveolar lavage fluid (BALF) after PAF inhalation in seven dogs. Airway responsiveness to inhaled methacholine was determined by modified Astograph (7Hz oscillation method). PAF (1000 mu/ml) was delivered as an aerosol, generated from a Devilbiss 646 nebulizer for ten minutes. Airway responsiveness to inhaled methacholine increased significantly 3 hr after PAF inhalation (p less than 0.01). After PAF inhalation, neutrophil and eosinophil counts in BALF increased significantly (p less than 0.01), and the levels of thromboxane (Tx)B2 in BALF also increased (p less than 0.05). Pretreated AA-861 significantly inhibited the increase of airway responsiveness after PAF inhalation (p less than 0.01). The increase of neutrophil and eosinophil counts in BALF after PAF inhalation was also inhibited significantly by pretreated AA-861 (p less than 0.01). The levels of TxB2 in BALF did not change after PAF inhalation following pretreatment with AA-861. These results suggest that 5-lipoxygenase products play important roles in the increase of airway responsiveness and in the infiltration of inflammatory cells into the airway after PAF inhalation in dogs. TxA2 released from inflammatory cells may be involved in the increase of airway responsiveness induced by PAF inhalation. PMID- 1854259 TI - [Effect of histamine on electrical properties in canine tracheal epithelium]. AB - To characterize the action of histamine on ion transport across the airway mucosa, we measured the electrical properties of cultured tracheal epithelium from dogs by Ussing's short-circuited technique in vitro. The addition of histamine to the submucosal side increased short-circuit current (Isc), whereas mucosal addition of histamine had no effect. The histamine-induced increase in Isc was dose-dependent with the maximal increase from the baseline value and EC50 being 4.4 +/- 0.5 microA/cm2 and 10(-6) M, respectively. We also tested the effects of pharmacological blocking agents on the histamine-induced Isc increase. The effect of histamine on Isc was partially inhibited by pretreatment of cells with amiloride, furosemide and diphenylamine carboxylate. Furthermore, the effect of histamine was inhibited by pyrilamine, but not by cimetidine. To determine the contributions of several intracellular second messenger systems to the histamine induced increase in Isc, we studied the change of Isc by pretreatment of cells with indomethacin, mepacrine and H-7. The increase in Isc produced by histamine was inhibited by indomethacin and mepacrine but not H-7. These results suggest that histamine stimulates both Cl secretion and Na absorption and may affect the subsequent movement of water across the airway epithelium through the activation of submucosal H1-receptor probably involving prostaglandin synthesis. PMID- 1854260 TI - Health for all through research. AB - John F. Kennedy's vision of man on the moon by the year 1970 set a goal for technological research and development. The World Health Organization's vision of health for all by the year 2000 set a similar goal not only for health policy but also for health research. Drawing on the analogy between these goals, this paper first explores what health for all means as a policy goal. It calls for changes in most aspects of the health care system. In the European Region of the World Health Organization, 38 specific targets show how approaches to health problems, lifestyles, environment, health care and various support measures (e.g., planning, management and training) should be changed to reach the over-all goal. These changes should be based on sound scientific knowledge. Health for all therefore also calls for a health research policy and reorientation of research. The second part of the paper looks at the research implications of health for all. Assisted by the Regional Office of the World Health Organization, the European Advisory Committee for Health Research analysed the 38 targets to see what kind of research would help to achieve them. The result of this analysis were two publications: "Research Policies for Health for All" and "Priority Research for Health for All". The first volume explains why a country needs a health research policy. The second one identifies, target by target, research necessary to reach them. Translated into several languages, they have begun to influence national research policies. The third section of the paper describes the research priorities identified in the two research for health for all volumes. It also aims at showing their relevance for the European health research community. It finally discusses the prerequisites that the countries have to set up to make research for health for all possible. They include changes in the incentives for and financing of research, personnel development, research organization and communication between the researchers and decision-makers. PMID- 1854261 TI - [Circadian variation in alertness, readiness for work and work efficiency]. AB - Among various rhythmic processes with different frequencies (periods), which are present in the human organism, for normal functioning the most important are the rhythms with a cycle length of about 24 hours (termed circadian rhythms). Circadian rhythms have been confirmed at all levels of physiological functions: from subcellular and cellular mechanisms, to the organic systems and organism on the whole. In normal everyday circumstances the rhythmic processes in the human organism are synchronised with the rhythmic processes in the environment. The external rhythmic variations support internal synchronisation between various rhythms, and in that way make it possible for the organism to better adapt to the environment. The sleep--wake rhythm is inverted during night work: the worker has to work in the period of low activity level, and sleep during the day, when he is usually active and alert. In order to work in shifts the worker has to adapt to such disruptions of the sleep--wake pattern. Tolerance to shift work was found to be associated with some features of the worker. The measurement of such features could serve as determinate of interindividual differences in shift work tolerance level. PMID- 1854262 TI - [The effect of a preventive health care program in a textile plant]. AB - A two-month field experiment was carried out on a sample of 95 women spinners and weavers in a textile plant. In the experimental group, which consisted of 54 workers, a programme of four preventive health measures was applied. The workers were asked to wear a combination of ear-muffs and cotton-wool offering optimal hearing protection and to take up individual mini programmes of physical exercise at work; they were offered a meal of the Pliva dietetic preparation Vitamalt before work and Donat-Mg natural mineral water from Zdravilisce Rogaska Slatina as a magnesium supplement. The measures from the programme were accepted and respected by 85-94% of the workers. As a result, fatigue at work was significantly reduced, and the subjectively estimated work satisfaction was markedly improved. A statistically insignificant trend towards the rise of productivity was also noticed during the period of programme application. PMID- 1854263 TI - Granulocyte reserve in chronic experimental benzene poisoning in rats. PMID- 1854264 TI - The effect of dose on maternal-foetal transfer of fluoride in rabbits. AB - Placental transfer of fluoride was investigated by fluoride determination in the bones and teeth of newborn rabbits whose mothers had been treated with fluoride during pregnancy. The mothers were given doses of 0, 0.10, 0.52 and 1.05 mmol fluoride per kg body weight as sodium fluoride, from the 16th day after conception to the end of pregnancy. All the doses produced a significant increase of fluoride level in the bones and teeth of newborn rabbits, indicating that the placenta was no barrier for the passage of fluoride. PMID- 1854265 TI - [Work capacity evaluation in inorganic lead exposure]. AB - When estimating the work ability of workers exposed to inorganic lead four zones should be differentiated: a zone of normal exposure (I), a zone of abnormal but acceptable exposure (II), a zone of abnormal but still acceptable exposure (III) and a zone of abnormal and unacceptable exposure (IV). In the zone of normal exposure specific work ability is preserved. In zones of abnormal but acceptable exposure specific work ability can, also, be preserved. However, in the zone of abnormal, unacceptable exposure specific work ability, temporarily or permanently, is lost. Combinations of three relevant laboratory tests are presented, which, while warning of the presence, i.e. the effect, of inorganic lead in the organism, directly dictate the estimation of specific work ability (blood lead, ALAD, EP, ZPP). Attention has been drawn to other contraindications, set by positive legislation, which also directly dictate the estimation of workers exposed to inorganic lead. It is emphasized that permanent disruption of relevant laboratory parameters (blood lead, ALAD, EP, ZPP) is a sufficient basis for recognizing occupational lead poisoning, within positive legislation. PMID- 1854266 TI - [Determination of aluminum in serum using electrothermal atomic absorption spectrophotometry]. AB - A simple and sensitive method for the determination of aluminium in human serum by electrothermal atomic absorption spectrophotometry has been developed. In view of contradictory data in literature all relevant analytical conditions have been tested. The method involves simple dilution with a 0.05% solution of Triton X-100 and atomization on the wall of a pyrolytically coated graphite tube. The sensitivity of the method is about 1 microgram/L and precision less than 11%. The method of standard addition is recommended for calibration, but the use of a calibration curve based on serum with a low content of aluminium is also possible. PMID- 1854267 TI - [Mutagenic and carcinogenic effects of vinyl chloride monomers in humans]. AB - The use of vinyl chloride monomer in industry dates back to the late 1930s. Today the number of occupationally exposed industrial workers is estimated to be several million. After the first described cases of cancer among workers exposed to high concentrations of this gas, extensive research was initiated into its possible mechanism of action on the living organism. This paper is a review of some current knowledge about the action of vinyl chloride monomer as a substance which after metabolic activation in the organism becomes a strong carcinogenic and mutagenic agent. PMID- 1854268 TI - [Diagnosis of transplanted heart acute rejection on the basis of endomyocardial biopsy morphologic examination]. AB - Results of morphological diagnosis of acute rejection on the material of 265 endomyocardial biopsies from 26 patients after an orthotopic donor heart transplantation are presented. The structural characteristics of different stages of acute rejection are given which is revealed in 85.7% observations. Ultrastructural myocardial changes in the early postoperative period not connected with the acute rejection crisis but resulting from a reperfusion cardiomyocytes damage are described. Results of electron microscopic examination of myocardium in rejection crisis are also given. PMID- 1854269 TI - [Immunomorphologic diagnosis of early myocardial necrosis using monoclonal antibodies to desmin and vimentin]. AB - Apart from monoclonal antibodies against cytoskeleton proteins, polyclonal antibodies to gamma-globulin and immunoglobulin G were used. Mosaicism of myocardial damage was observed: the intermittence of acute necrosis foci with areas of ischemia and normal myocardium. Desmin may serve a marker of early necrosis in the myocardium. PMID- 1854270 TI - [Alterations of the myocardium and adrenergic nerves of the isolated rat heart under conditions of total ischemia and normothermic cardioplegic reperfusion]. AB - The increase of the ischemic period from 30 to 60 min did not enhance the degree of the contractural myocardial damage in connection with progression of "no reflow" phenomenon. Endogenous catecholamines do not play a decisive role in genesis of ischemic (reperfusion) heart damage. Cardioplegic reperfusion with a high K+ content results in a considerable loss of mediator from the adrenergic nerve fibres thus leading to the partial isolated heart desympathization. PMID- 1854271 TI - [Role of monocytes-macrophages in atherogenesis]. AB - The study of the coronary arteries atherogenesis with the use of scanning and transmission electron microscopy was performed on the material of emergency necropsies of 45 patients who suffered the primary cardiovascular pathology. The transformation of macrophages into the foamy cells were studied in vitro with the use of peritoneal mouse macrophages and modified LDL labelled with colloidal gold as well as a method of phase-contrast cinemicrography. Two types of macrophages were distinguished ultrastructurally: scavenger-macrophages participating in the phagocytosis of lipoproteins and transforming into the foamy cells and secreting macrophages determining vascular wall homeostasis and ensuring the T-lymphocyte inclusion into the immune reactions and the contact with target cells. Balanced cell kinetics and cytokine secretion at early stages of atherosclerosis determine whether the lipid spot would regress or would transform into the atherosclerotic plaque. PMID- 1854272 TI - [Interorgan relationships in alcoholic intoxication]. AB - It is suggested, on the basis of 315 necropsies of patients who died of drunkenness and alcoholism and examination of 300 rats with acute and chronic alcoholic intoxication, to distinguish an "alcoholic disease" as a separate nosological entity. The stages of this disease are drunkenness, alcoholism and alcoholic abstinence syndrome. Multiple organ pathology is characteristic for the disease with obligatory microangiopathy, alcoholic encephalo-, cardiomyo- and hepatopathy. The development of the disease follows a principle of vitium cordis at which the changes in certain organs result in the progression of pathological lesions in other organs. The course of the disease is characterized by periods of remission and exacerbation provoked either by a regular alcohol consumption or by an alcoholic abstinence syndrome. Toxic effects of alcohol, acetaldehyde and catecholamines are main factors in the pathogenesis of lesions in various organs. PMID- 1854273 TI - [Ultrastructural analysis of aortic endothelium after the host's death]. AB - The changes of the endothelium of abdominal and thoracic aorta of rats and man (71 Wistar rats and 4 humans) during different periods after the death of the organism were analysed by means of scanning and transmission electron microscopy. Soon after death of the organism endotheliocytes are shortened and the cytoskeleton is structuralized. The changes result from hypoxia and the reaction develops within 60 minutes after death. Aortic endothelium is heteromorphic in its sensitivity to hypoxia. In the segments with high hemodynamic loads to the vessel wall the injury of endothelium develops more rapidly. The conversion from reversible to irreversible changes includes certain stages. In spite of different structure of rat and human aortic wall the stages of the endothelial injury after death and the time of beginning of irreversible injury are similar. PMID- 1854274 TI - [Secretory immunoglobulin A and pyloric helicobacteriosis in patients with duodenal ulcer]. AB - 57 patients with duodenum ulcer were examined. Secretory immunoglobulin A (SIgA) was determined by an immunofluorescent method in the gastric and duodenum mucosa depending on the population size of pyloric helicobacter (HB). The frequency of SIgA detection in the gastric mucosa depends on the HB population size: when it is considerable SIgA was not detected in 41% cases. SIgA was detected in the gastric mucosa without pathological lesions in 85% cases, in atrophic gastritis in 70% and in superficial gastritis in 54% cases. PMID- 1854275 TI - [Disturbance of epithelial proliferation of the gastro-intestinal tract mucosa in ulcers and erosion]. AB - Epithelial proliferation in the mucosa of the gastro-intestinal tract was studied autoradiographically with 3H-thymidine under the following conditions: acute gastric ulcers as complication of acute pancreatitis; exacerbation of duodenal ulcer; ulcers and erosions in bacterial dysentery. Mucosa of practically healthy persons as well as mucosa of patients with the same diseases not complicated with ulcers and erosions served as control. Biopsies of mucosa were taken 2 cm from ulcers and erosions. The decrease of DNA-synthesizing nuclei number in the mucosa epithelium at early stages of ulcer formation was observed in all these conditions. PMID- 1854276 TI - [Routes of resorption of peritoneal fluid in the diaphragm in liver cirrhosis (morphologic study)]. AB - The diaphragm peritoneum from 12 operated patients and 34 patients who died from liver cirrhosis with or without ascites was studied by means of light microscopy and electron transmission and scanning microscopy. Considerable lesions are found in the peritoneum: cuboidization of mesothelial cells, basal membrane thickening, dilation of stomata, lymphatic lacunae and collectors lumina. Liver cirrhosis with ascites is frequently followed by lymphatic vessels thrombosis and firm attachment of the diaphragm to the liver resulting in the inhibition of the ascitic liquid elimination. Thus both the enhancement of liquid transudation into the abdominal cavity and the disturbance of the drainage function of the diaphragm peritoneum take place. PMID- 1854277 TI - [Immunohistochemical characteristics of the epithelial transformation zone in the uterine cervix using monoclonal antibodies against various epithelial markers]. AB - Epithelium transformation zone in the uterine cervix was studied by means of monoclonal antibodies (MAB) against cytokeratin (CK) peptides, epithelial membrane antigen (EMA) and skin granular layer proteins. It is shown that in the region of epithelial junction metaplastic epithelium is, as a rule, observed which possesses a unique spectrum of CK distinct from that in the ecto--and endocervix. The features of the expression of CK N8, N17, EMA in metaplasia are described. MAB EE 2I-06 against CK N1, 2, 9-11 and MAB G 36-19 are suggested as markers of the metaplastic epithelium maturity in the uterine cervix. PMID- 1854278 TI - [Sepsis and local inflammatory processes in infants: mathematical approach to pathomorphological differential diagnosis]. AB - The structure of thymus, spleen, adrenal and thyroid glands and changes in peripheral white blood cells formula were studied in 97 cases of sepsis and local inflammatory processes (LIP) in infants. A complex of differential diagnostic features of sepsis and LIP was defined. Mathematical use of the complex significantly increases the objectivity of sepsis and LIP diagnosis. PMID- 1854279 TI - [Development of endometrial cancer in one half of a double uterus]. AB - Two observations (patients of 52- and 48-years old) in which endometrial carcinoma developed in one half of a double uterus. Tumours were highly differentiated and completely replaced a left half of the uterus. The endometrium of the right half was with no change. 52-year--old patients had endometrioid carcinoma of the right ovary as well. PMID- 1854280 TI - [Necrotic medulloepithelioma of the eye]. AB - An exceptionally rare case of the ciliary body medulloepithelioma is described. The distinctive feature of this case was the subtotal necrosis of the tumour. The development of necrosis is attributed to the destruction of the lens capsule and lens fibres by tumour cells. It resulted in phako--anaphylactic endophthalmitis which is likely to have been the cause of the tumour necrosis. Possible immune and autoimmune mechanisms of inflammatory--destructive changes of the eye tissue and the tumour are discussed. PMID- 1854281 TI - [Use of the computer in the pathology department for improvement of the prophylactic medical examination and treatment of newborns and women]. AB - The practice of prognosis of the pathological conditions development in newborns on the basis of placenta examination and the evaluation of results by a computer is described. The same method was used for the determination of the risk groups among the women. The results of cytological diagnosis of some chronic infections on the basis of examination of endocervix and urethra smears are also presented. According to the authors the work performed helped in reducing the children mortality. PMID- 1854282 TI - [Establishment of a medical diagnosis]. PMID- 1854284 TI - Politics, pregnancy and profitability. PMID- 1854283 TI - [A method for storage and transportation of human and animal tissue specimens in a condition suitable for subsequent histochemical investigations]. AB - A method for storage and transportation of human and animal tissue specimens suitable for subsequent histochemical investigations is described. Tissue cut into pieces of 1 X 1 cm is placed into penicillin flask containing 60-80% glycerol in a saline. The flask is hermetically closed. In such a state tissue is preserved suitable for histochemical analyses (including those for oxidative reduction enzymes) and routine histological investigations, various fixation procedures and paraffin and celloidin embedding for 30 days at room temperature. PMID- 1854285 TI - Optimal axillary thermometer placement time for recording neonatal temperature. PMID- 1854286 TI - It is often argued that nurses are an oppressed group in society. PMID- 1854287 TI - Ethanol and acetaldehyde concentrations in pregnant rats after administration of ethanol. AB - Concentrations of ethanol and acetaldehyde in 20- day pregnant rats were determined following administration of ethanol. A single dose of 2 g ethanol/kg body weight was given via stomach tube and a rat was sacrificed every hour for 8 hours. In both the blood and livers of mother and fetus ethanol, concentrations were maximal at 2 hrs after administration, and the ethanol concentration-time curves were virtually identical during the 8 hrs. There was a time lag in the appearance of ethanol in the amniotic fluid, as compared with the appearance in the maternal and fetal blood and liver. Also, the ethanol concentration in the amniotic fluid was higher than that in the maternal and fetal blood during hours 4 to 8. Acetaldehyde was found in maternal blood, fetal blood, and amniotic fluid at concentrations at least 1000-fold lower than the ethanol concentrations, and was variable. For each biological fluid the acetaldehyde and ethanol concentration-time curves were not parallel. The acetaldehyde concentration in the maternal blood was about 10-fold greater than in the fetal blood. These data indicate that ethanol administered to pregnant rats undergoes unimpeded bidirectional placental transfer between the mother and fetus and that the amniotic fluid may serve as a reservoir for ethanol in utero. PMID- 1854288 TI - [Secondary development of psychological dependence in a methamphetamine dependent]. AB - A case of methamphetamine dependence was presented, who had used a large amount of the drug for a long time during both of the first and the second period of its prevalence. He led a socially and psychologically stable life with neither drug habits nor episodes of flash-back phenomenon in 20's and 30's of his age. While in the former period of the prevalence, visual illusion had occurred in him 3 months after the first injection of the drug, in the latter, auditory hallucination occurred in a month after the initiation of the reinjection. This hallucination was so invasive and persistent that he became insomniac and could not keep stable daily life. Recently the auditory hallucination has disappeared by the reinjection of the drug, resulting in releasing him from the sufferings like insomnia, and then promoting the drug use more frequently. Even at the law court to decide the penalty against his illegal drug use, he recurrently insisted that methamphetamine was his necessity in order to be freed from the hallucination and keep stable daily life. He declared his intention not to abandon his drug habit in spite of any punishments. On the central nervous system (CNS) depressants such as the morphine- and barbiturate-type drug, the psychological dependence is brought about secondarily by the mechanism to avoid the withdrawal symptoms. On the other hand, the secondary development of psychological dependence through avoidance of the chronic toxicity by the acute drug effect itself, should be considered as one of the characteristics of the CNS stimulants like methamphetamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854289 TI - General practitioner's health--a non event. PMID- 1854290 TI - Influenza vaccination: is it worth it? AB - Australian government policy is to offer influenza vaccine every autumn to all Australians over the age of 65 and to those of any age who suffer from any chronic condition that predisposes to serious complications following influenza. Despite this clear advice from NHMRC and the financial incentives provided by Medicare and the PBS, less than one in three of this vulnerable cohort receives the vaccine. In this article the medical profession is exhorted to encourage and facilitate influenza vaccine delivery to the old and to the frail. PMID- 1854291 TI - Managing viral upper respiratory infections. AB - The epidemiology of the common cold is reviewed with the aim of providing helpful advice for patients. Future management will include limiting the spread of the cold virus by attention to the mode of transmission and the development of anti viral drugs, of which interferon holds the most promise. PMID- 1854292 TI - Chronic suppurative otitis media. AB - Chronic suppurative otitis media refers to those ears in which the ear drum has a chronic non healing perforation. The perforation may or may not be associated with ossicular fixation or necrosis, middle ear infections, tympanosclerosis or mastoiditis. It is a disease commonly found in lower socio-economic areas and is particularly prevalent worldwide in groups with low living standards. PMID- 1854293 TI - Which antibiotic and when. AB - Initial empirical antibiotic therapy for infection requires knowledge of the likely causative organism and its expected antibiotic susceptibilities. By definition, initiation of such therapy is required before culture results are available. Although antibiotic therapy appears complex and confusing owing to the ever increasing list of new agents, the factors to consider before choosing an antibiotic remain the same. This article looks at these factors and presents treatment choices for some common infections. PMID- 1854295 TI - Signs, symptoms, and the new descriptors. AB - Data from 143 consultations in general practice were assessed by factors relevant to the four-category descriptive system developed by the Royal Australian College of General Practitioners. It seems that there is no relationship between consultation length, apparent symptom seriousness or the occurrence of a physical examination. Suggestions are offered for improving the clarity of consultation descriptor categories. PMID- 1854294 TI - Competency of medical students in general practice procedural skills. AB - A self-reported competency survey of 1988 sixth year medical students in Queensland revealed that only 2 of 47 procedural skills considered essential for general practice had been performed alone by 80 per cent or more of students. Six of the essential skills had not been performed by more than 80 per cent of students. Consideration needs to be given to the content and effectiveness of undergraduate general practice procedural skills training. PMID- 1854296 TI - Cervical cytology in central Australian Aboriginal women. AB - Cervical smears were taken from 113 Aboriginal women who attended an Aboriginal community controlled health service in Alice Springs for gynaecological, obstetric or other unrelated conditions over a 6 month period. Nine women (8%) had cervical atypia and two (1.8%) had cervical intraepithelial neoplasia. These rates are similar to those observed among other population groups in larger Australian and overseas studies, as was the high prevalence of abnormal smears in women under 25 years of age (11% of this age group). Urban dwellers had a higher prevalence of abnormal smears (15%) compared with town camp and rural women (2%). This pilot study emphasises the importance of routine screening for central Australian Aboriginal women and identifies possible risk groups for further research. PMID- 1854297 TI - The RACGP William Conolly Oration 1990. Personality, the profession and change. PMID- 1854298 TI - Conversion of a medical records system. AB - The author describes the conversion of a practice's medical records from the old card system to the RACGP record system. The exercise has resulted in improved patient care and, at the same time, enabled the partners to satisfy the requirements for a Quality Assurance option. PMID- 1854300 TI - Patient education. Making your marriage work. PMID- 1854299 TI - It could only happen in Papua New Guinea. PMID- 1854301 TI - Intercostal nerve block. PMID- 1854302 TI - Onychogryphosis. PMID- 1854303 TI - The health of general practitioners. A pilot survey. AB - A pilot survey of the health behaviour of West Australian general practitioners revealed a lack of adherence by doctors to accepted preventive health measures. Medical care in the group was not well structured, with many GPs self medicating. Levels of psychological distress in the surveyed sample exceeded 50 per cent. PMID- 1854304 TI - Samuel Charles Fitzpatrick. AB - Samuel Fitzpatrick, MBE, CBE, was an outstanding general practitioner and surgeon in the Western District of Victoria for 50 years. He became a world authority on the surgical management of hydatid disease. He is also an accomplished and prolific painter, especially in watercolours. Many of his works are displayed in the Hamilton Art Gallery, Victoria. PMID- 1854305 TI - Sinus rhythm. PMID- 1854306 TI - Before your very eyes. PMID- 1854307 TI - Pain in the leg. AB - Pain in the leg is a common yet confusing problem. It has many causes, varying from a simple cramp to an arterial occlusion. Overuse of the leg, as in athletic competitions, can lead to a multiplicity of painful leg syndromes, once again varying from simple sprains and strains of soft tissue to compartment syndromes. This paper presents an overview of the causes of painful lower limit, especially the more general causes, without discussion of specific areas such as the knee and foot. PMID- 1854308 TI - Post menopausal osteoporosis. Part 2: Treatment and prevention. AB - Part 1 of this two part series on post menopausal osteoporosis, which appeared in AFP April 1991, presented the diagnostic features of osteoporosis. Part 2 outlines the modern concepts of treatment and prevention. PMID- 1854309 TI - A variant of HELLP syndrome. PMID- 1854310 TI - Chlamydia tests. PMID- 1854311 TI - Comparison of live avirulent M-9, Minnesota, and CU fowl cholera vaccines. AB - The M-9 and Minnesota (MN) avirulent Pasteurella multocida vaccines were evaluated and compared with the Clemson University (CU) vaccine, which had been shown to be highly effective in preventing fowl cholera in turkeys. Neither the M 9 nor the MN vaccine given in the drinking water was as effective as the CU vaccine in protecting turkeys against challenge with virulent P. multocida. When grown in brain-heart infusion (BHI) agar as recommended, the M-9 was not as efficacious as when it was grown in BHI broth. The M-9 was as effective as the CU vaccine only when grown in BHI broth and given at 10 times the standard dosage. Injection of the M-9 vaccine into the air spaces of the head at a site near the caudal rim of the ear after one vaccination in the drinking water was not as effective for hyperimmunizing potential breeders as was the CU vaccine injected at the same site. A microtiter agglutination test demonstrated a significant (P less than 0.05) correlation between the level of anti-P. multocida antibody found 1 week after vaccination and survival after challenge with virulent P. multocida. PMID- 1854312 TI - Economic effects of subclinical chicken anemia agent infection in broiler chickens. AB - To evaluate the economic effects of subclinical chicken anemia agent (CAA) infection on broiler performance, clinically normal broiler flocks were grouped into two categories: A) flocks in which none of 10 birds sampled at slaughter had antibody to CAA, and B) flocks in which six or more of 10 similarly sampled birds had CAA antibody. Production and performance parameters of 25 flocks in each category were compared. No statistically significant differences were found between category A and category B flocks in major production parameters such as sex, feed manufacturer, type of litter, stocking density, and age at slaughter. However, category A flocks achieved 13% (P less than 0.05) greater net income per 1000 birds, 2.0% better feed-conversion ratio (P less than 0.05), and 2.5% (P less than 0.05) greater average weight per bird than category B flocks. No significant differences in hockburn bonus per 1000 birds (a bonus payable to growers whose broilers have the lowest prevalence of contact dermatitis lesions on the hocks) and mortality were found between category A and category B flocks. These results show that subclinical CAA infection has a substantial, statistically significant effect on commercial broiler performance and profitability. PMID- 1854313 TI - An enzyme-linked immunosorbent assay for detection of Bordetella avium infection in turkey flocks: sensitivity, specificity, and reproducibility. AB - An enzyme-linked immunosorbent assay (ELISA) for detection of Bordetella avium infection in turkey poults was developed. One-week-old poults challenged intratracheally with 10(12) colony-forming units of B. avium had detectable titers (greater than or equal to 11), with an average of 13.6% positive samples when the birds were 6 to 11 weeks old. The method was sensitive enough to detect maternal antibodies to B. avium in poults up to 3 weeks of age. The same poults challenged at 1 week of age had 100% tracheal infection up to 3 weeks of age, which dropped to 0% by 6 weeks. The method resulted in no false-positive samples (titer = 0) from birds not infected with B. avium and tested weekly between 4 and 11 weeks of age. Antibodies in turkey flocks infected with Newcastle disease virus, hemorrhagic enteritis virus, and Mycoplasma meleagridis, and birds infected with Escherichia coli had no apparent cross-reactivity to the B. avium antigens used in the ELISA. The percentages of B. avium-positive serum samples collected from different turkey flocks did not significantly differ (P greater than 0.05) when samples were tested by the developed ELISA at different times, an indication of the reproducibility of the method. PMID- 1854314 TI - Use of an enzyme-linked immunosorbent assay to measure antibody levels in turkey breeder hens, eggs, and progeny following natural infection or immunization with a commercial Bordetella avium bacterin. AB - Twelve large white turkey hens were immunized with a commercially available Bordetella avium bacterin. Hens and eggs were tested using an enzyme-linked immunosorbent assay (ELISA) to determine the response to the bacterin. Three hundred poults were then obtained from two commercial flocks, the hens of one flock having been immunized with the same bacterin used on the group of 12 turkeys. Titers of the poults were monitored for 7 weeks, and poults were challenged by exposure to infected poults at 1, 7, 14, and 21 days post-hatch. Hens produced an antibody response following immunization, with a parallel antibody response being detected in eggs. Maternal antibodies were present in poults from immunized hens. Poult titers declined to near the level of poults from unimmunized hens by 14 days of age. Poults from immunized hens challenged at 1 and 7 days were resistant to development of clinical disease and gross lesions, whereas all poults from unimmunized hens exhibited clinical signs and gross lesions. After 14 days, the resistance of both groups to development of clinical disease, became near equal, neither group being affected as severely as the unimmunized hens challenged at days 1 and 7. Six commercial turkey breeding flocks and their progeny that had not been vaccinated for B. avium and had no history of B. avium infection were evaluated with the B. avium ELISA. There were variations between the flocks, with poult titers reflecting those found in the hens. PMID- 1854315 TI - Effect of feeding selected carbohydrates on the in vivo attachment of Salmonella typhimurium in chick ceca. AB - Two-day-old chicks were orally inoculated with 1 ml of Salmonella typhimurium (10(5) colony-forming units/ml) and divided into four groups. Three groups were fed 2.5% carbohydrates starting on day 1 (arabinose, galactose, and lactose), while the fourth group served as the control. Ceca were obtained from each group at 7, 14, and 21 days. At the end of 14 days, all three carbohydrates statistically reduced Salmonella recovery. However, lactose failed to reduce recovery between day 14 and day 21. Arabinose and galactose continued to show significant reductions of recovery through 21 days. No statistical difference was found between Salmonella recovery from whole ceca (with cecal material) and inverted ceca (washed free of cecal material). PMID- 1854317 TI - Effect of anaerobic cecal microflora and dietary lactose on colonization resistance of layer chicks to invasive Salmonella enteritidis. AB - The effect of oral inoculation with anaerobic cultures of cecal microflora and providing lactose in the feed on colonization resistance to invasive Salmonella enteritidis was evaluated in newly hatched leghorn chicks. Salmonella colonization of the ceca, tissue invasion and organ colonization, horizontal transmission, and seroconversion were significantly decreased (P less than 0.01) in chicks inoculated with cecal flora. The addition of lactose to the feed, in the absence of cecal microflora, failed to provide protection. Dietary lactose enhanced colonization resistance in chicks that were inoculated with anaerobic cultures of cecal flora. The results indicated that establishment of normal cecal flora in layer chicks together with the addition of lactose to the diet markedly increases resistance to cecal colonization and organ invasion, and decreases horizontal transmission of S. enteritidis. PMID- 1854316 TI - Immunobinding assay for the speciation of avian mycoplasmas adapted for use with a 96-well filtration manifold. AB - An immunobinding assay capable of distinguishing among Mycoplasma synoviae, M. gallisepticum, M. gallopavonis, and M. meleagridis was developed. A low-protein binding membrane filter served as the solid support, and a 96-well microsample filtration manifold was used. The assay detected 50 ng of mycoplasmal protein, or approximately 3 x 10(4) colony-forming units, from pure or mixed cultures. No cross-reactions were observed among the mycoplasma species tested. The assay was inexpensive, easy to interpret, and required approximately 3 hr to perform. The 96-well format allowed screening of numerous cultures and use of several antisera in a single assay. PMID- 1854318 TI - Effect of fasting on plasma thyroid and adrenal hormone levels in turkey poults infected with Bordetella avium. AB - Plasma triiodothyronine (T3), thyroxine (T4), and corticosterone (CS) were measured in fasted and nonfasted control and Bordetella avium-infected poults. The stress of B. avium infection increased plasma CS, and fasting for 24 hours caused a further significant increase in CS levels. Plasma T3 was not affected by the infection, but fasting caused a significant reduction in both control and infected poults. Plasma T4 of fasted poults was increased in both control and infected groups, but infection attenuated the plasma T4 response. Total iodothyronines were increased in the control-fasted poults more than in infected fasted poults, indicating a reduced responsiveness to stress by the thyroids of infected poults. Changes in plasma thyroid hormones and CS partially explain the decreased body weight gain and decreased body temperature after exposure to B. avium. PMID- 1854319 TI - Reduced erythrocyte deformability as a possible contributing factor to pulmonary hypertension and ascites in broiler chickens. AB - Deformability of erythrocytes and hematological parameters in white leghorn and broiler chickens were measured at age 7, 14, 21, 28, and 35 days. For deformability testing, a simple vertical apparatus containing a polycarbonate membrane with 5-microns pores was used. This technique assesses erythrocyte deformability by measuring the filtration time of an erythrocyte suspension through the pores. There was a significant difference in filtration time between the leghorns and broilers at all sampling times. These results indicate that reduced erythrocyte deformability in broilers may be one of the predisposing factors that increase resistance to blood flow and alter the rheology of blood in the microcirculation in the lung. Increased resistance to flow may result in pulmonary hypertension, heart failure, and ascites in broiler chickens. PMID- 1854320 TI - Effect of a live reovirus vaccine on reproductive performance of broiler breeder hens and development of viral tenosynovitis in progeny. AB - A live commercial reovirus vaccine, Enterovax, was administered to adult broiler breeder hens via the drinking water to determine its efficacy in stimulation of circulating antibody. This vaccine was compared with a commercial inactivated reovirus vaccine. Only the inactivated product resulted in increased antibody as measured by a commercial enzyme-linked immunosorbent assay. However, the live reovirus vaccine caused diarrhea in the hens and decreased eggshell quality, fertility, and hatchability. In addition, the live vaccine virus was vertically transmitted from hens to their progeny, resulting in increased embryonic mortality and viral tenosynovitis. PMID- 1854321 TI - Comparison of three velogenic strains of Newcastle disease virus by RNA oligonucleotide fingerprinting. AB - The purified RNA from three velogenic strains of Newcastle disease virus (Ca-1083 [Fontana], Largo, and Texas GB) was analyzed by oligonucleotide fingerprinting. An image-processing system used to manipulate and rescale autoradiographs to uniform dimensions assisted the manual comparison of RNA fingerprints. Based on this analysis, the fingerprints of the Largo and Ca-1083 viscerotropic strains were more similar to each other than either virus was to the Texas GB neurotropic strain. By contrast, the Largo and Texas GB strains displayed more differences in the pattern of RNA fragment migration than other strain comparisons. Fingerprint comparisons were also performed between velogenic and previously reported lentogenic strains of NDV. No large RNA fragments were identified as NDV-specific or virulence-specific. This study evaluates the relationships among these NDV strains. PMID- 1854322 TI - In vivo antigen expression by Pasteurella multocida. AB - Pasteurella multocida was purified from the blood of turkeys affected with acute fowl cholera, and membrane preparations from those bacteria were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized on immunoblots. Antigens were detected in the membranes of these in vivo-propagated bacteria that were not detected in membrane preparations of the same P. multocida strain grown in vitro. The unique antigens were detected in the detergent insoluble phase and were enriched to various degrees by different detergents. PMID- 1854323 TI - Evaluation of radiolabeled and colorimetric DNA probes in comparison with an antigen screening assay for the detection of Salmonella from poultry farms. AB - A total of 48 environmental drag-swab samples from various poultry farms were tested for the presence of Salmonella spp. by culture, an enzyme-linked immunosorbent assay-based Salmonella antigen screening (SAS) assay, and two DNA probes (radiolabeled and colorimetric). The radiolabeled DNA probe was allowed to hybridize with culture-positive samples (n = 8) and was found to detect Salmonella spp. in all cases (100%). Both of the probes, subsequently hybridized with culture-negative samples (n = 8), were observed to yield good agreement (91%) with the culture findings. The remaining samples (n = 32) were tested by the SAS assay, and where there was no agreement between the culture and SAS, samples were further examined by the DNA probes. Results using both probes agreed with those obtained by culturing the samples but did not agree with the SAS assay result when the ratio of samples tested to samples positive (S/P) cutoff value used was 0.5. PMID- 1854324 TI - Health survey of backyard poultry and other avian species located within one mile of commercial California meat-turkey flocks. AB - A survey was conducted to characterize domestic and exotic bird populations, estimate seroprevalence to selected disease agents, and describe health management practices on 62 premises containing "backyard" flocks located within one mile of 22 commercial California meat-turkey flocks participating in National Animal Health Monitoring System (NAHMS). Chickens were present on 56 backyard premises and turkeys on seven. Antibodies were identified against Mycoplasma gallisepticum, M. synoviae, M. meleagridis, Salmonella pullorum, Newcastle disease virus, avian encephalomyelitis virus, Bordetella avium, hemorrhagic enteritis virus, infectious bronchitis virus, and infectious bursal disease virus in 367 blood samples from 32 backyard premises. Twenty-two owners of backyard premises said they restricted visitor contact with their birds, and two required visitors to wear rubber boots and use boot disinfectant. Owners of seven premises used biologics and/or pharmaceutics for disease prevention. One family member worked on a commercial turkey ranch, but no other contact between owners, relatives, or employees and commercial poultry was reported. PMID- 1854325 TI - Late clinical expression of lameness related to associated osteomyelitis and tibial dyschondroplasia in male breeding turkeys. AB - A sudden outbreak of lameness related to transport stress is described in a flock of male breeding turkeys. Most of the affected turkeys exhibited obvious unilateral leg disorders. All were affected with tibial or metatarsal dyschondroplasia with at least one lesion associated with a large focus of necrosis. By histological examinations, bone lesions showed the typical feature of osteomyelitis. The inflammatory bone lesions appeared at only single isolated sites and were always associated with obvious sequestra of dyschondroplastic retained cartilage. Osteomyelitis seems to be an unexpected acute complication of previous dyschondroplasia in relation with different breeding stress situations. The resulting pain of the associated lesions could be the main cause of clinical expression of lameness. The pathogenesis of the phenomenon remains uncertain. PMID- 1854326 TI - Systemic trichomoniasis in a squab operation. AB - Systemic trichomoniasis was responsible for severe morbidity and mortality in a commercial squab operation. Squabs of 1 to 3 weeks of age were primarily affected. Extensive caseous necrosis of the liver, heart, lung, and intestinal mesentery was observed grossly. Histologically, extensive heterophilic inflammation surrounded the necrotic areas and was observed perivascularly in areas that were uninvolved grossly. Numerous trichomonads were demonstrated in affected tissues with Bodian's silver stain. PMID- 1854327 TI - Interaction between mRNA, ribosomes and the cytoskeleton. PMID- 1854328 TI - Metabolism of inositol phosphates in ATP-stimulated vascular endothelial cells. AB - The accumulation of InsP1, InsP2, InsP3 and InsP4 isomers was investigated in bovine aortic endothelial cells labelled with [3H]inositol and stimulated with ATP. The separation of these isomers was performed by ion-pairing reverse-phase h.p.l.c. on a mu Bondapack C18 column for the InsP3 and InsP4 isomers and by ion exchange h.p.l.c. on a Partisil SAX column for the InsP1 and InsP2 isomers. In unstimulated endothelial cells, a large amount of material was co-eluted with InsP5 and InsP6, whereas amounts of InsP3 and InsP4 were small. The addition of ATP (100 microM) induced a striking (35-fold stimulation) and transient increase of Ins(1,4,5)P3 that was maximal around 15 s. This peak was followed by a more sustained accumulation of Ins(1,3,4,5)P4 and Ins(1,3,4)P3, but the amounts of these two metabolites accumulated in response to ATP were much smaller than that of Ins(1,4,5)P3. The increase in InsP2 isomers in response to ATP had similar characteristics: a rapid and transient accumulation of Ins(1,4)P2, followed by an increase of Ins(3,4)P2 and Ins(1,3)P2, which was more sustained but had a smaller magnitude. ATP also induced the accumulation of both Ins1P and Ins4P, but with different time courses: the level of Ins4P was maximal at 1 min (60 times the control value) and returned to baseline after 5 min, whereas the increase in Ins1P was undetectable at 1 min and reached a maximum after 5 min, which represented 240% of the basal level. These data indicate that Ins(1,4,5)P3, which is rapidly formed in aortic endothelial cells as a result of activation of P2Y receptors, is preferentially metabolized at early times (less than 1 min) by a 5 phosphatase, with the sequential formation of Ins(1,4)P2 and Ins4P. Afterwards, a small but sustained increase in the content of Ins(1,3,4)P3, Ins(1,3)P2, Ins(3,4)P2 and Ins1P was observed, reflecting the activation of the Ins(1,4,5)P3 3-kinase. PMID- 1854329 TI - Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Protective effects of ascorbic acid. AB - Cigarette smoke (CS) is known to contain a large number of oxidants. In order to assess the oxidative effects of CS on biological fluids, we exposed human blood plasma to filtered (gas phase) and unfiltered (whole) CS, and determined the rate of utilization of endogenous antioxidants in relation to the appearance of lipid hydroperoxides. Lipid peroxidation was measured with a specific and sensitive assay that can detect lipid hydroperoxides at plasma levels as low as 10 nM. We found that exposure of plasma to the gas phase of CS, but not to whole CS, induces lipid peroxidation once endogenous ascorbic acid has been oxidized completely. In addition, CS exposure caused oxidation of plasma protein thiols and albumin-bound bilirubin, whereas uric acid and alpha-tocopherol were not consumed at significant rates. In plasma exposed to the gas phase of CS, low density lipoprotein exhibited slightly increased electrophoretic mobility, but there was no apparent degradation of apolipoprotein B. Our results support the concept of an increased vitamin C utilization in smokers, and suggest that lipid peroxidation induced by oxidants present in the gas phase of CS leads to potentially atherogenic changes in lipoproteins. PMID- 1854330 TI - A large accumulation of non-muscle myosin occurs at first entry into M phase in rat vascular smooth-muscle cells. AB - Vascular smooth-muscle cells (VSMCs) from rat aortae contained very little non muscle myosin heavy chain (MHC) immediately after dispersal, and the protein did not accumulate if the cells were held in G0/G1 phase by withholding serum or were held in first S phase by the addition of bromodeoxyuridine (BrdU). However, non muscle MHC accumulated by greater than 20-fold per cell during first M phase, when over 80% of the cells divided between 48 h and 72 h after addition of serum. Delaying the addition of serum caused a delay in the accumulation of the non muscle MHC until the cells subsequently entered M phase. If the cells were held in M phase at the metaphase/anaphase boundary by nocadazole, the accumulation of non-muscle myosin still occurred, although division was blocked. When the cells were pulse-labelled with [35S]methionine, it was found that non-muscle MHC was one of the major proteins being made and that its synthesis occurred at similar rates throughout the cell cycle. This implied that the rate of degradation of the protein before first M phase was much faster than in M phase, when the protein accumulated rapidly. This was confirmed by direct measurements of the rate at which [35S]methionine-labelled non-muscle MHC disappeared from the cells, which gave a half-life for the protein of about 8 h before M phase but about 5 days in post-mitotic cells, i.e. an increase of approx. 15-fold. These data are consistent with the hypothesis that there is a mechanism in VSMCs which shortens the half-life of the protein before first M phase and that the accumulation of non-muscle MHC which results from the increase in half-life at first M phase may be necessary for division of these cells. PMID- 1854331 TI - Lipoylation of the E2 components of the 2-oxo acid dehydrogenase multienzyme complexes of Escherichia coli. AB - The number of functional lipoyl groups in the dihydrolipoyl acetyltransferase (E2) chain of the pyruvate dehydrogenase multienzyme complex from Escherichia coli has been re-assessed by means of a combination of protein-chemical and mass spectrometric techniques. (1) After the complex had been treated with N-ethyl[2,3 14C]maleimide in the presence of pyruvate, the lipoyl domains were excised from the complex, treated with NaBH4 and re-exposed to N-ethyl[2,3-14C]maleimide. All the chemically reactive lipoyl groups in the native complex were found to be catalytically active. (2) Proteolytic digests of the separated lipoyl domains were examined for the presence of the lipoylation-site peptide, GDKASME, with and without the lipoyl group in N6-linkage to the lysine residue. Only the lipoylated form of the peptide was detected, suggesting that all three lipoyl domains are fully substituted at this site. (3) The behaviour of each lipoyl domain was examined on ion-exchange chromatography in response to alkylation with 4 vinylpyridine after either chemical reduction of the lipoyl group with dithiothreitol or reductive acetylation by the pyruvate dehydrogenase complex in the presence of pyruvate. All three domains exhibited a quantitative shift in retention time, confirming that each domain was fully substituted by an enzymically reactive lipoyl group. (4) When subjected to electrospray mass spectrometry, each domain gave a mass consistent with a fully lipoylated domain, and no aberrant substitution of the target lysine residue was detected. The same result was obtained for the lipoyl domain from the E. coli 2-oxoglutarate dehydrogenase complex. (5) Previous widespread attempts to assess the number of functional lipoyl groups in the pyruvate dehydrogenase multienzyme complex, which have led to the view that a maximum of two lipoyl groups per E2 chain may be involved in the catalytic mechanism, are in error. PMID- 1854332 TI - Expression and site-directed mutagenesis of hepatic glucokinase. AB - Soluble rat liver glucokinase was expressed at high levels at 22 degrees C in the BL21(DE3)pLysS strain of Escherichia coli. Aspartate-211 of yeast hexokinase has been implicated as a catalytic residue from crystallographic data. The corresponding residue in rat liver glucokinase, aspartate-205, was mutated to alanine and the expressed mutant had 1/500th of the activity of the wild type, with no change in the Km values for glucose or ATP. The results support a role for this residue as a base catalyst in the glucokinase reaction and, most probably, a similar role in the reactions of all members of the hexokinase family. PMID- 1854333 TI - Kinetic studies on protoporphyrinogen oxidase inhibition by diphenyl ether herbicides. AB - Diphenyl ethers (DPEs) and related herbicides are powerful inhibitors of protoporphyrinogen oxidase, an enzyme involved in the biosynthesis of haems and chlorophylls. The inhibition kinetics of protoporphyrinogen oxidase of various origins by four DPEs, (methyl)-5-[2-chloro-4-(trifluoromethyl)phenoxy]-2 nitrobenzoic acid (acifluorfen and its methyl ester, acifluorfen-methyl), methyl 5-[2-chloro-4-(trifluoromethyl) phenoxy]-2-chlorobenzoate (LS 820340) and methyl 5-[2-chloro-5-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid (RH 5348), were studied. The inhibitions of the enzymes from maize (Zea mays) mitochondrial and etiochloroplastic membranes and mouse liver mitochondrial membranes were competitive with respect to the substrate, protoporphyrinogen IX, for all four molecules. The relative efficiencies of the inhibitors were: acifluorfen-methyl greater than LS 820340 much greater than RH 5348 greater than or equal to acifluorfen. The four molecules showed mixed-competitive type inhibition of the enzyme from yeast mitochondria where acifluorfen, a carboxylic acid, had the same inhibitory activity as its methyl ester, acifluorfen-methyl, and both were much greater than that of LS 820340 and RH 5348. PMID- 1854334 TI - Comparison of the activity and conformation changes of lactate dehydrogenase H4 during denaturation by guanidinium chloride. AB - The inactivation and unfolding of lactate dehydrogenase (LDH) during denaturation by guanidinium chloride (GuHCl) under diverse conditions have been compared. Unfolding of the native conformation, as monitored by fluorescence and c.d. measurements, occurs in two stages with increasing GuHCl concentrations, and the inactivation approximately coincides with, but slightly precedes, the first stage of unfolding. The enzyme is inhibited to about 60-70% of its original activity by cross-linking with glutaraldehyde or in the presence of 1 M-(NH4)2SO4, with its conformation stabilized as shown by the requirement for higher GuHCl concentrations to bring about both inactivation and unfolding. Low concentrations of GuHCl (0.2-0.4 M) activate the cross-linked and the (NH4)2SO4-inhibited enzyme back to the level of the native enzyme. For the enzyme stabilized by (NH4)2SO4 or by cross-linking with glutaraldehyde, inactivation occurs at a markedly lower GuHCl concentration than that required to bring about its first stage of unfolding. It is concluded that the active site of LDH is situated in a limited region relatively fragile in conformation as compared with the molecule as a whole. The GuHCl activation of LDH stabilized in (NH4)2SO4 or by cross-linking with glutaraldehyde suggests that this fragility and consequently flexibility of the active site is required for its catalytic activity. PMID- 1854335 TI - Assembly of chick brain MAP2-tubulin microtubule protein. Characterization of the protein and the MAP2-dependent addition of tubulin dimers. AB - The principle proteins present in twice-cycled chick brain microtubule protein were characterized. The protein consists of a stoichiometric mixture of MAP2 and tubulin, together with a number of minor components. Its composition remains unaltered after a third cycle of assembly in a buffer supplemented with 67 mM NaCl, with the exception of the phosphorylation of MAP2 to a low level (congruent to 1 mol.mol-1). The inclusion of 67 mM-NaCl dissociates the MAP2-tubulin oligomers, and restricts the assembly to the MAP2-dependent addition and loss of tubulin dimers, such that the assembly kinetics approximate to a simple pseudo first-order reaction. The assembled microtubules exhibit dynamic instability, with no evidence for end-to-end annealing. PMID- 1854336 TI - Kinetics of GTP hydrolysis during the assembly of chick brain MAP2-tubulin microtubule protein. AB - The kinetics of GTP hydrolysis during microtubule assembly have been examined using chick brain MAP2-tubulin microtubule protein in a NaCl-supplemented buffer. The elongating microtubules terminate in a 'GTP cap', since the kinetics of GTP hydrolysis are slower than those of subunit addition. GTP hydrolysis is (a) stoichiometric, (b) occurs as a vectorial wave as the initial rate of hydrolysis is proportional to the molar concentration of microtubule ends and not to the initial rate of subunit addition, and (c) either does not occur, or occurs only at a much lower rate, in the terminal subunits. PMID- 1854337 TI - Assembly of chick brain MAP2-tubulin microtubule protein. Analysis of tubulin subunit flux rates by immunofluorescence microscopy. AB - A filter-based immunofluorescence-microscopy method for obtaining microtubule lengths has been developed and evaluated. Kinetic constants and mean lengths obtained show close agreement with those obtained by complementary methods applied to chick brain MAP2-tubulin microtubule protein in NaCl-supplemented buffer. The filter-based method has been used to estimate tubulin subunit flux (Jon) resulting from isothermal dilution of microtubule populations to various free tubulin concentrations, (c). This experimental Jon(c) plot is significantly different from that predicted by a variety of theoretical models, but is consistent with a 'lateral cap' model of dynamic instability [Bayley, Schilstra & Martin (1990) J. Cell. Sci. 95, 33-48] adapted to accommodate the observed vectorial GTP hydrolysis. PMID- 1854338 TI - D-Xylose (D-glucose) isomerase from Arthrobacter strain N.R.R.L. B3728. Purification and properties. AB - D-Xylose (D-glucose) isomerase was purified to homogeneity in yields of approx. 1 g/kg of wet cells from a strain of Arthrobacter that produces it as about 10% of total soluble protein. It is a tetramer of identical 43,114 Da subunits containing a preponderance of acidic residues and no cysteine. Partial protein sequences were determined as a step to gene cloning. It requires Mg2+, Co2+ or Mn2+ for activity, Mg2+ being best; Ca2+ is an inhibitor, competitive with Mg2+. It is a good D-glucose isomerase with kcat. 1200 min-1 at pH 8 at 60 degrees C, which is higher than that of any other enzyme of this class. L-Arabinose, D ribose and D-lyxose are poor substrates, with kcat. 78, 31 and 3.7 min-1 respectively at pH 8 at 30 degrees C, compared with 533 min-1 for D-xylose. Xylitol is a true competitive inhibitor for D-xylose (Ki 0.3 mM), but D-sorbitol shows mixed inhibition (Ki 6.5 mM). For D-fructose the pH optimum at 60 degrees C is 8, and at pH 7 the Arrhenius activation energy is 75 kJ/mol over the range 30 70 degrees C. PMID- 1854339 TI - D-Xylose (D-glucose) isomerase from Arthrobacter strain N.R.R.L. B3728. Gene cloning, sequence and expression. AB - Arthrobacter strain N.R.R.L. B3728 superproduces a D-xylose isomerase that is also a useful industrial D-glucose isomerase. The gene (xylA) that encodes it has been cloned by complementing a xylA mutant of the ancestral strain, with the use of a shuttle vector. The 5' region shows strong sequence similarity to Escherichia coli consensus promoters and ribosome-binding sequences and allows high levels of expression in E. coli. The coding sequence shows similarity to those for other D-xylose isomerases and is followed by 22 nucleotide residues with stop codons in each reading frame, a good 'consensus' ribosome-binding site and an open reading frame showing similarity to those of known D-xylulokinases (xylB). Studies on the expression of the cloned gene in Arthrobacter and in E. coli suggest that the two genes are part of a xyl operon regulated by a repressor that is defective in strain B3728. Codon usage in these two genes, and in another open reading frame (nxi) that was adventitiously isolated during early cloning attempts, shows some characteristic omissions and a strong G + C preference in redundant positions. PMID- 1854340 TI - Requirements for the inactivation of ribosomes by gelonin. AB - Inactivation of Artemia salina and rabbit ribosomes by gelonin requires ATP and a high-Mr factor present in the rabbit reticulocyte-lysate post-ribosomal supernatant. The kinetic constants of the gelonin-catalysed release of adenine from A. salina ribosomes are Km = 4.35 microM and Kcat. = 0.1 min-1 in the absence of cofactors, and Km = 1.15 microM and Kcat. = 108 min-1 in their presence. The last two values are similar to those measured for ricin A chain in the absence of cofactors (Km = 2.02 microM and Kcat. = 317 min-1). PMID- 1854341 TI - The Id gene is activated by serum but is not required for de-differentiation in rat vascular smooth muscle cells. AB - Primary rat vascular smooth muscle cells cultured on fibronectin in the absence of serum lost smooth-muscle-specific myosin heavy chain but did not enter the cell cycle and proliferate until they were stimulated by serum. Under these conditions accumulation of Id mRNA occurred only in response to serum and was maximal during the G1 phase of the cycle. PMID- 1854342 TI - Effect of cold acclimation on GSH, antioxidant enzymes and lipid peroxidation in brown adipose tissue. AB - Cold acclimation increased the activities of superoxide dismutase, catalase, total and selenium (Se)-dependent glutathione peroxidases (GPx) and glutathione reductase by 2-4-fold in the brown adipose tissue (BAT) of cold-acclimated rats. Nevertheless, when expressed per unit protein, the antioxidant enzyme activities were unaltered. Sensitivity to lipid peroxidation and GSH levels both increased by one order of magnitude in the cold on a per weight basis and were still 3-5 times greater in the cold when expressed per mg of protein. We suggest that activation of BAT leads to a large increase in the potential for lipid peroxidation and that the tissue responds to this challenge by increasing practically all of its antioxidant defences. Nevertheless, GSH, and possibly GPx activity, seem to be the principal defences involved in adaptation of the tissue to a higher sensitivity to peroxidative damage after activation. PMID- 1854343 TI - Distinction between endo-oligopeptidase A (EC 3.4.22.19) and soluble metalloendopeptidase (EC 3.4.24.15) PMID- 1854344 TI - Thimet oligopeptidase (EC 3.4.24.15): the same by any name? PMID- 1854345 TI - Analysis and physiological implications of renal 2-oxoglutaramate metabolism. AB - The relative significance of the flux through the glutamine aminotransferase (glutaminase II) pathway to renal ammoniagenesis is poorly understood. A basic and unresolved question is whether 2-oxoglutaramate (2-OGM), a product of the glutaminase II reaction, is deamidated to yield 2-oxoglutarate and NH3, or whether 2-OGM accumulates as an unreactive lactam, depending on the environmental pH. In the current studies we utilized 13C n.m.r. as well as 15N n.m.r. as well as 15N n.m.r. to demonstrate that 2-OGM occurs as a lactam, i.e. 5 hydroxypyroglutamate, regardless of the environmental pH. Our additional aims were to determine whether human kidney cells (HK cells) in culture can produce 2 OGM and to ascertain a pH-dependent relationship between NH3 and 2-OGM production from glutamine. We therefore developed an isotope dilution assay for 2-OGM utilizing 5-hydroxy[4-13C,1-15N]pyroglutamate as the labelled species. Incubations of HK cells in minimal essential medium supplemented with 1 mM-[2 15N]glutamine demonstrated significantly higher production of 2-OGM at pH 6.8 and lower production at pH 7.6 compared with pH 7.4. Similarly both 15NH3 and [15N]alanine formation were significantly higher in acute acidosis (pH 6.8) and lower in acute alkalosis (pH 7.6) compared with that at physiological pH. Addition of 1 mM-amino-oxyacetate to the incubation medium at pH 7.4 significantly diminished [15N]alanine and 2-OGM production, but the production of 15NH3 via the glutamate dehydrogenase pathway was significantly stimulated. The current observations indicate that the glutaminase II pathway plays a minor role and that flux through glutamate dehydrogenase is the predominant site for regulation of ammoniagenesis in human kidney. PMID- 1854346 TI - Processing of the precursor of protamine P2 in mouse. Peptide mapping and N terminal sequence analysis of intermediates. AB - Protamine P2, the major basic chromosomal protein of mouse spermatozoa, is synthesized as a precursor almost twice as long as the mature protein, its extra length arising from an N-terminal extension of 44 amino acid residues. This precursor is integrated into chromatin of spermatids, and the extension is processed during chromatin condensation in the haploid cells. We have studied processing in the mouse and have identified two intermediates generated by proteolytic cleavage of the precursor. H.p.l.c. separated protamine P2 from four other spermatid proteins, including the precursor and three proteins known to possess physiological characteristics expected of processing intermediates. Peptide mapping indicated that all of these proteins were structurally similar. Two major proteins were further purified by PAGE, transferred to poly(vinylidene difluoride) membranes and submitted to automated N-terminal sequence analysis. Both sequences were found within the deduced sequence of the precursor extension. The N-terminus of the larger intermediate, PP2C, was Gly-12, whereas the N terminus of the smaller, PP2D, was His-21. Both processing sites involved a peptide bond in which the carbonyl function was contributed by an acidic amino acid. PMID- 1854347 TI - Transport of taurine and its regulation by protein kinase C in the JAR human placental choriocarcinoma cell line. AB - The JAR human placental choriocarcinoma cell line transports taurine, concentrating it over 1000-fold inside the cell. The transport system is energized by a Na+ gradient and exhibits an absolute requirement for Cl-. Neutral beta-amino acids such as beta-alanine and hypotaurine effectively compete with the system, whereas neutral alpha-amino acids such as alanine, leucine and alpha aminoisobutyric acid do not. The transport system interacts with gamma aminobutyric acid to an appreciable extent. Kinetic analysis reveals that the taurine transport system in this cell line is of a high-affinity and low-capacity type (apparent dissociation constant 2.3 +/- 0.3 microM; maximal velocity 88.5 +/ 5.0 pmol/3 min per mg of protein). Pretreatment of the JAR choriocarcinoma cells with phorbol 12-myristate 13-acetate results in the inhibition of the taurine transport system in a dose-dependent manner. The inhibition is blocked by co treatment of the cells with staurosporine, an inhibitor of protein kinase C. The inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate, has no effect on the transport system. These data show that the choriocarcinoma cells express a taurine transporter with characteristics similar to those of the taurine transporter described in the normal human placenta, and that the activity of the transporter in these cells is under the regulatory control of protein kinase C. PMID- 1854348 TI - Processing of prothrombin in the secretory pathway. AB - Antibodies raised against plasma prothrombin and the prothrombin propeptide were used to identify prothrombin precursors in rough and smooth microsomes and in the Golgi apparatus. The data demonstrate that the propeptide is part of the prothrombin molecule when undergoing a variety of modifications in the Golgi apparatus. It is shown that these modifications result in an increase in the apparent molecular mass of the prothrombin precursor from 78 kDa in early processing to 83 kDa in late processing. The 83 kDa prothrombin precursor was not recognized by the anti-propeptide antiserum and most likely represents the final product of the precursor in the secretory pathway. Evidence is presented that the propeptide is released from the parent molecule in the Golgi apparatus by a membrane-bound Ca(2+)-dependent serine proteinase(s) with characteristics similar to those of the proalbumin-to-albumin-converting enzyme. Vitamin K-dependent carboxylase activity was measured in membrane fragments obtained from the Golgi apparatus preparation. Sucrose-density-gradient centrifugation and the use of marker enzymes showed that carboxylase activity was highest in fractions enriched in cis-Golgi cisternae. Two different synthetic peptides were used as substrates for the carboxylase. These peptides were from the N-terminal and the C-terminal part of the gamma-carboxyglutamic acid (Gla) region of prothrombin. It is shown that the N-terminal and the C-terminal peptides were preferred as substrates for the carboxylase in the microsomal and the Golgi apparatus preparations respectively. It is also shown that the prothrombin precursor acquires negative charges in the Golgi apparatus that do not result from addition of sugars in late processing. These negative charges could be eliminated by thermal decarboxylation, suggesting that Gla residues may also be synthesized in late processing. PMID- 1854349 TI - Rat and human neutrophil N-formyl-peptide chemotactic receptors. Species difference in the glycosylation of similar 35-38 kDa polypeptide cores. AB - Rat and human neutrophil N-formyl-peptide chemotactic receptors were subjected to glycosidase and proteinase treatments to determine the extent and species differences of glycosylation and the carbohydrate requirement in the high affinity ligand binding. N-Formyl-Nle-Leu-Phe-Nle-125I-Tyr-Lys was attached to rat and human neutrophils either before or after glycosidase and proteinase treatments, and the labelled receptors were solubilized after glutaraldehyde cross-linking and analysed by SDS/PAGE and autoradiography. Both the rat and human N-formyl-peptide chemotactic receptors contain only N-linked oligosaccharides, as demonstrated by their sensitivity to peptide N-glycosidase F (PNGase F) and resistance to O-glycanase treatment. The N-linked oligosaccharides seem to be of the complex type rather than the high-mannose or hybrid type and lack terminal sialic acid, as demonstrated by their resistance to endoglycosidases D and H and neuraminidase treatments. This sensitivity pattern was similar in both species, and the shift in the molecular size of the receptors to 35-38 kDa after PNGase F treatment occurred through one intermediate product, suggesting that both receptors contain a similar 35-38 kDa polypeptide core with two N-linked complex-type oligosaccharides, the heterogeneity of which is responsible for the species difference in receptor size. Papain treatment alone or followed by PNGase F produced in both species a 33-36 kDa membrane-bound fragment that was still able to bind the ligand, suggesting that the oligosaccharides are located on the approx. 2 kDa papain-cleavable polypeptide fragment of the receptors. The cleavage sites for both papain and PNGase F were hidden in occupied receptors, suggesting a conformational or topographical change in these upon ligand binding. Scatchard analyses and cross-linking experiments demonstrated that carbohydrates are not required for high-affinity ligand binding and that the 33-36 kDa membrane-bound papain fragment of both receptors contains the ligand-binding site. PMID- 1854350 TI - Characterization of proteoglycans synthesized by human adult glomerular mesangial cells in culture. AB - 1. The newly synthesized proteoglycans from human adult glomerular mesangial cells labelled in vitro for 24 h with [35S]sulphate have been characterized using biochemical and immunological techniques. 2. The following proteoglycans were identified (% of total synthesized). (i) A large chondroitin sulphate proteoglycan, CSPG-I, Mr approximately 1 x 10(6) (10.6%). This proteoglycan consisted of a protein core of Mr approximately 4 x 10(5) and glycosaminoglycan chains of Mr 2.5 x 10(4), and was present in both the cell layer and the culture medium. (ii) A major small dermatan sulphate proteoglycan, DSPG-I, Mr 3.5 x 10(5) (46%), which was mainly located in the culture medium. (iii) A second minor small dermatan sulphate, DSPG-II, Mr approximately 2 x 10(5) (9.8%). This molecule was exclusively located in the culture medium. (iv) A large heparan sulphate proteoglycan, HSPG-I, Mr 8 x 10(5) (3.3%). (v) A second large heparan sulphate proteoglycan HSPG-II, Mr approximately 6 x 10(5) (23%). HSPG-I and HSPG-II were extracted from both the culture medium and the cell layer. 3. Western blot analysis of the core proteins released by chondroitin ABC lyase treatment of DSPG I and DSPG-II identified these dermatan sulphate proteoglycans as biglycan and decorin respectively. Both DSPG-I and DSPG-II had core proteins of Mr 45,000. 4. The cell-layer-associated forms of CSPG-I, HSPG-I and HSPG-II were accessible to limited trypsin treatment, bound to octyl-Sepharose and could be inserted into liposomes, indicating a possible cell membrane location. 5. Pulse-chase experiments indicated that the cell-layer-associated [35S]proteoglycans undergo limited metabolism to inorganic [35S]sulphate, the majority of which is accounted for by the degradation of HSPG-II and to a lesser extent DSPG-I. PMID- 1854351 TI - Effect of Mg2+ on the binding of oxytocin to sheep myometrial cells. AB - Binding isotherms of oxytocin to sheep myometrial cells in a short-term cell culture were investigated in the presence of Mg2+ in the concentration range 0-10 mM. The occurrence of at least three binding sites had been demonstrated earlier. Mg2+ influences individual sites and individual features of the binding isotherm differently. Dissociation constants (Kd) of the high- and medium-affinity sites attain a minimum of 6.8 x 10(-10) and 4.2 x 10(-8) mol/l respectively at 2.75 mM Mg2+. The two sites display the highest binding capacity (B) at 1 mM-Mg2+ (ratio of high affinity/medium affinity is 1:16). The B/Kd quotients reflecting relative binding (bound-to-free concentration) at the half-saturation of binding sites also have their maxima at 1 mM-Mg2+. The high-affinity site displays a strong positive co-operativity (Hill coefficient at 4 mM-Mg2+ of 2.4), which is amplified in the presence of Mg2+. Positive co-operativity of the medium-affinity site is markedly lower (Hill coefficient at 4 mM-Mg2+ of 1.5) and shows less dramatic Mg(2+)-dependence. Low-affinity sites are not co-operative at any Mg2+ concentration. It is concluded that Mg2+ may display its effect upon the oxytocin receptor interaction predominantly by influencing positive co-operativity. PMID- 1854352 TI - Calcium uptake by leukemic and normal T-lymphocytes exposed to low frequency magnetic fields. AB - Calcium-ion uptake by normal and leukemia lymphocytes increased during a 30-min exposure to a 13.6 Hz, sinusoidal magnetic field at 20 microT peak. The time varying field was horizontal and parallel to a 16.5 microT component of the ambient static magnetic field. The uptake of 45Ca2+ increased 102% in a line of murine, cytotoxic T-lymphocytes (C57B1/6-derived CTLL-1), increased 126% in freshly-isolated spleen lymphocytes (C57B1/6 mice), and increased 75% in a line of lymphoma cells (C57B1/6-derived EL4). In contrast, there was no effect when the same field was applied for 30 min immediately before--as opposed to during- incorporation of calcium ions. When spleen lymphocytes were exposed during incubation with 45Ca2+ to a 60 Hz magnetic field at 20 microT peak, a small but statistically significant increase (37%) in uptake of the labeled ions occurred. These results indicate that weak, alternating magnetic fields might affect calcium-dependent functions of normal and leukemic lymphocytes. PMID- 1854353 TI - Miniature-probe measurements of electric fields and currents induced by a 60-Hz magnetic field in rat and human models. AB - A miniaturized probe was designed and built to provide detailed data on fields induced by a uniform 60-Hz magnetic field in homogeneous models of rat and human. The probe employed three silver wires twisted and potted in an 8-cm hypodermic needle. The exposed tips of the wires formed three sensing electrodes with a centered ground; highly sensitive voltage measurements were enabled by a lock-in amplifier. Tests were conducted in a 1-mT rms field that was uniform within +/- 5%. The models were made by casting 1.5% agar at 1-S/m conductivity into plastic foam molds. The rat model was scaled 1:1 as an adult (22 cm length; mass about 640 g). The human model was scaled 1:4 as an adult (height = 46.5 cm; mass 1.4 kg). The probe was inserted into each model in several regions, and readings of induced fields were made under different exposure geometries. Maximal strengths of fields induced near the surface of the torso were as high as 120 microV/cm in the laterally exposed rat model. Data extrapolated from the quarter-scale human model revealed that an induced field as high as 700 microV/cm could occur at the torso of a frontally exposed human adult. An overall size-scale factor of about 5 appears to be appropriate for experimental exposures of rats that are intended to simulate currents induced in human beings by magnetic fields. The average strength of electric fields induced in the torso by a 1-mT magnetic field is comparable to that by a vertical electric-field at 60 kV/m and 28 kV/m, respectively, for the rat and human. PMID- 1854354 TI - The influence of temperature during electric- and magnetic-field-induced alteration of calcium-ion release from in vitro brain tissue. AB - A technique based on release of calcium ions from in vitro preparations of avian brain tissues has been used by several investigators to demonstrate a biological effect of weak electric and magnetic fields. When the tissues have been exposed to ELF-modulated, VHF or UHF fields, enhanced release of calcium ions has resulted. In contrast, when the tissues have been exposed directly to an ELF field, outcomes have differed. Both inhibition and enhancement in release of calcium ions have been reported. We now find that either outcome--or a null result--is possible, depending on the temperature of tissue samples before and during exposure. Avian-brain tissues were exposed to 16-Hz sinusoidal electromagnetic fields at 14.1 Vrms/m (in air) and 64 nTrms. During 20-min exposures, as tissue-sample temperature rose by 0.7 to 2.5 degrees C to a final temperature of 35, 36, or 37, but not of 38 or 39 degrees C, an enhanced release of ions was observed. When the temperature was stable during exposure (i.e., constant within +/- 0.3 degrees C) at a final value of 36 or 37, but not of 35 or 38 degrees C, the quantity of ions released was reduced. And when descending by 0.7 to 1.5 degrees C to any final temperature from 35 to 38 degrees C, a null result occurred. These findings may reconcile the apparent disagreement in the direction of a field-induced response, and they may explain why experimental outcomes have been difficult to confirm in some laboratories. Of greater importance, the findings may also provide insight into the mechanism of the field induced phenomenon. PMID- 1854355 TI - Immediate post-exposure effects of high-peak-power microwave pulses on operant behavior of Wistar rats. AB - Behavioral effects of high-peak-power microwave pulses on Wistar rats were studied by operant schedules. Each of twelve rats that had been trained to press a lever to receive food pellets was assigned randomly in groups of four to three different schedules of reinforcement: fixed-ratio (FR), variable-interval (VI), and differential-reinforcement-of-low-rates (DRL). After achieving a steady baseline performance, each animal was exposed for 10 min to 1.25-GHz microwave radiation at 1-MW peak-power (10-microseconds pulse width). Each pulse produced a peak whole-body SA and SAR of 2.1 J/kg and 0.21 MW/kg. Total doses (SAs) were set to 0.50, 1.5, 4.5, and 14 kJ/kg by adjusting the pulse-repetition rate. The corresponding time-averaged whole-body SARs were 0.84, 2.5, 7.6, and 23 W/kg. A microwave-transparent animal holder was used to keep the animal's body axis parallel to the E-field. Exposures at the highest dose caused an average colonic temperature rise of 2.5 degrees C and these animals failed to respond at all for about 13 minutes after the exposure. Their colonic temperatures had decreased to 1.1 degrees C, or less, above their pre-exposure (normal) temperature level when they began to respond. The FR and VI animals failed to reach their baseline levels of performance thereafter, while those on the DRL schedule displayed variable effects. No behavioral effects were found at the lower dose levels. It is concluded that the behavioral perturbations produced by pulsed microwave irradiation were thermal in nature. PMID- 1854356 TI - An increase in the negative surface charge of U937 cells exposed to a pulsed magnetic field. AB - Pulsed magnetic fields have been used to enhance healing of bone fractures and purportedly of lesions in soft tissue. However, their mechanism of action is poorly understood. We report changes in the plasma membrane of a nonadherent mammalian cell line, U937, which was exposed to a 25-pps magnetic field for 48 hours. Aqueous polymer two-phase partition studies showed that magnetic-field exposed cells exhibited an increased negative surface charge but membrane hydrophobicity was not significantly altered. The observed increase in membrane electronegativity of exposed cells did not reflect a significant change in growth rate. PMID- 1854357 TI - Lipid lowering therapy leads to a reduction in sodium-lithium countertransport activity. AB - Erythrocyte sodium-lithium countertransport (SLC) was measured in 17 patients with either combined hyperlipidaemia or hypercholesterolaemia before and after lipid lowering therapy. Before treatment SLC related to the serum triglyceride level and was increased in combined hyperlipidaemia. After treatment the SLC had returned to normal and the change in SLC was related to the change in serum triglyceride levels. Raised SLC is associated with essential hypertension but is not related to blood pressure. Therefore, the association of raised SLC with hyperlipidaemia and essential hypertension appears to have different underlying mechanisms. PMID- 1854358 TI - Relationship of arterial wall uptake of radiolabeled liposomes to the presence of monocyte/macrophage cells in the hypertensive and atherosclerotic arterial wall. AB - In vivo radiolabeled liposome uptake in 5 sham-operated, 7 coarctation-induced hypertensive, and 8 atherosclerotic arterial walls from New Zealand White rabbits was compared to determine the mechanism of arterial wall uptake of liposomes. Uptake between the three groups was significantly different (P less than 0.001) with a 3-fold difference in uptake between the sham-operated and hypertensive groups and the hypertensive and atherosclerotic groups. Liposome uptake was significantly higher in the atherosclerotic group of animals (P less than 0.05). Avidin-biotin immunoperoxidase staining for monocyte/macrophage cells revealed that liposome uptake increased concomitantly with arterial wall monocyte/macrophage cellular invasion and that liposome localization, determined by autoradiography, paralleled the monocyte/macrophage cellular distribution in both hypertensive and atherosclerotic arterial walls. This study provides the first direct evidence that liposomes can escape from the circulation and enter the diseased arterial wall. Furthermore, it suggests that one possible mechanism of arterial wall uptake of liposomes is via the monocyte/macrophage cell which avidly and preferentially engulfs liposomes and then passively carries them into the arterial wall during hypertensive and atherosclerotic lesion development. Liposomes could potentially be used to carry agents into the arterial wall in the study of arterial wall lesion development. PMID- 1854359 TI - The ratio of ankle and arm arterial pressure as an independent predictor of mortality. AB - We carefully ascertained deaths for a cohort of 744 patients who had undergone noninvasive testing for lower extremity peripheral arterial disease (PAD) in a university affiliated, community hospital. Using a ratio of the ankle and brachial blood pressures (ABI) of less than 0.85 as the criteria, the relative risk (RR) for total mortality associated with PAD was 2.36 (95% CL = 1.60, 3.48) after adjusting for baseline covariates in a proportional hazards model. There was a strong trend for increasing risk with decreasing ABI (P less than 0.0001). Specific causes of death for which survival was directly related to the magnitude of ABI were myocardial infarctions, and deaths other than vascular disease and cancer. There was no relationship between ABI and the risk of mortality from cancer. The mortality experience of those with normal ABI was very similar to that of the general U.S. population (age adjusted RR = 1.14, 95% CL = 0.78, 1.61), whereas the risk for those with an ABI less than 0.4 was markedly elevated in comparison to the U.S. population (RR = 4.49, 95% CL = 3.52, 5.64). Our results suggest that the relatively technically simple measure of the ratio of ankle to brachial blood pressures, if low, carries a very poor prognosis and should prompt investigation and treatment of atherosclerotic disease in other vascular systems. PMID- 1854360 TI - Serum selenium and coronary heart disease risk factors in southern Italian men. AB - The association between serum selenium concentration and a number of coronary heart disease risk factors is studied in 364 males from southern Italy participating in the Olivetti Heart Study. Selenium correlates positively and significantly with serum cholesterol (r = 0.120; P = 0.022), and this positive association persists after adjustment for age and body mass index. Selenium levels in heavy smokers are lower than both light smokers and current non smokers, but these differences do not reach statistical significance. Selenium is not significantly associated with any of the other CHD risk factors (e.g., triglycerides, HDL cholesterol, blood pressure, age, and body mass index). It is hypothesized that the association between selenium and serum cholesterol reported in this and previous studies could be due to dietary interrelationships between selenium intake and foods that affect serum cholesterol concentrations. PMID- 1854361 TI - Effects of fluvastatin (XU 62-320), an HMG-CoA reductase inhibitor, on the distribution and composition of low density lipoprotein subspecies in humans. AB - We studied the effect of fluvastatin (XU 62-320), a new HMG-CoA reductase inhibitor, on the distribution of low density lipoprotein (LDL) subspecies and composition in humans. As expected, fluvastatin significantly lowered serum LDL levels (25% after 6 weeks of therapy). In addition, treatment with fluvastatin changed the LDL subspecies. In the group treated with fluvastatin, 38.5% of the individuals showed changes in the shape of LDL absorbance profile obtained from density gradient ultracentrifugation and 54% of the group showed changes in the electrophoretic mobility of the LDL bands. Of those showing changes in electrophoretic mobility, the majority (78%) shifted to slightly larger, less dense LDL after drug therapy. However, the LDL-cholesterol/apo B ratio changes were relatively small in all fluvastatin-treated individuals including the group with changes in electrophoretic mobility, confirming that HMG-CoA reductase inhibitor causes relatively small and subtle changes in the distribution of LDL subspecies. PMID- 1854362 TI - Platelet membrane fluidity in type IIA, type IIB and type IV hyperlipoproteinemia. AB - Fluorescence spectroscopy, a very sensitive index for measuring the biophysical properties of living cell systems, was used to examine the structural order of intact, resting, gel-filtered platelets from hyperlipidemic subjects (n = 48, 25 70 years) and normolipemic subjects (n = 34, 19-68 years). Fluorescence anisotropy (r[s]), which is inversely related to membrane fluidity, was estimated using 3 different fluorescent dyes, DPH, TMA-DPH, and 6-AS, known to label different regions of biological membranes. Increased membrane fluidity was observed in type IIB (n = 24, 36-62 yrs; r[s] = 0.0692 +/- 0.09) and type IV (n = 10, 33-57 yrs; r[s] = 0.058 +/- 0.006) hyperlipidemics in comparison to type IIA (n = 14, 25-70 yrs; r[s] = 0.086 +/- 0.019) and control subjects (n = 24, 28-68 yrs; r[s] = 0.079 +/- 0.012). The temperature dependency of r[s]-DPH values was significantly different (P less than 0.01) in platelets from type IIB and type IV patients compared to type IIA and control subjects of similar age. A significant positive correlation (P less than 0.005) between membrane fluidity and age was found only in healthy control subjects (n = 34, 19-68 yrs). Despite significant (P less than 0.01) differences in plasma lipid concentrations in hyperlipidemic patients and controls, significant ex vivo relations between membrane fluidity and lipoprotein concentrations, free fatty acid distribution, and increased age were found only in healthy control subjects. Plasma levels of thromboxane as well as serum selenium concentrations did not significantly differ between hypercholesterolemic, hypertriglyceridemic, and control subjects. PMID- 1854363 TI - Cholesterol metabolism in hypercholesterolemia-resistant rabbits. AB - Normal rabbits typically respond to a diet high in cholesterol with a large increase in the concentration of plasma cholesterol. We have previously described the breeding and partial characterization of a variant rabbit which does not respond to a high cholesterol diet with changes in plasma cholesterol concentration. In the present report we have characterized three components involved in cholesterol homeostasis: the B/E (LDL) receptor, 3-hydroxy-3 methylglutaryl coenzyme A reductase activity (HMG-CoA reductase, EC 1.1.1.34) and acyl-coenzyme A: cholesterol acyltransferase activity (ACAT, EC 2.3.1.26) in the livers of the hypercholesterolemia-resistant rabbits. Using normal cholesterol fed rabbit [125I] beta-VLDL as a ligand, liver membranes prepared from resistant rabbits fed a low-cholesterol diet had 70% higher binding capacity than membranes from normal rabbits fed the same diet. Similar experiments demonstrated that the resistant rabbits had a 240% higher B/E receptor binding capacity compared to normal animals when liver membranes were prepared from animals fed a 0.25% cholesterol-enriched diet. No difference in the binding affinity of [125I]beta VLDL was detected in membranes prepared from normal or resistant animals. When fed a low-cholesterol diet, the resistant rabbits had approximately 2-fold higher hepatic HMG-CoA reductase activity (97.4 +/- 3.5 pmol product/mg/min in resistant animals compared to 45 +/- 1.1 pmol product/min/mg in normal animals). The difference was exaggerated in animals fed the 0.25% cholesterol-enriched diet, 73.3 +/- 5.5 vs 2.4 +/- 0.56 pmol product/min/mg for resistant and normal membranes respectively. The basal activity of ACAT in hepatic membranes was significantly lower in the resistant rabbits compared to normal rabbits (138 +/- 11 vs 268 +/- 19 pmol cholesteryl ester/min/mg in resistant and normal rabbits respectively); when fed a 0.25% cholesterol-enriched diet, the enzyme was induced 6-fold in normal animals but was increased only 2-fold in the resistant animal. These biochemical data suggested that the resistant rabbit maintained low intracellular cholesterol even when fed a cholesterol-enriched diet. Direct measurement of cellular cholesterol and cholesteryl esters demonstrated that the concentration of these lipids was significantly lower in the resistant animal than in normal animals with the largest differences found in the cytoplasmic rather than the membrane compartment. These studies demonstrate that the resistant rabbit manifests several quantitative differences in cholesterol metabolism and in the regulation of cholesterol metabolism; but these studies do not directly explain the underlying cause of the resistance to hypercholesterolemia in the resistant rabbit. PMID- 1854364 TI - Calcification of aortic wall in cholesterol-fed rabbits. AB - Development of the mineralization process in the course of atherogenesis was studied using the cholesterol-fed rabbit model. The aorta samples were investigated by means of proton and electron microprobes, infrared spectroscopy and X-ray diffraction as well as selected histochemical staining. Blood serum was analysed every 2 weeks to determine the content of cholesterol, triglycerides, inorganic phosphorus, ionized calcium, elemental composition as well as activity of alkaline phosphatase. It was found that the administered diet did not disturb the calcium and phosphorus homeostasis. Histochemical findings confirmed the formation of lipid-rich lesions blocking the lumen of the vessel. The dystrophic calcification was observed only in the atheroma, while in the tunica media a slight mineralization similar to that found in controls was observed after 210 days of the diet. In the atheroma the only phase detected was a defective hydroxyapatite. The perfection of the crystals, as well as the diameter of the deposits, increased during the course of the diet reaching about 2 microns after 210 days. The crystals were not contaminated with carbonate groups regardless of the duration of the diet. PMID- 1854365 TI - Effect of insulin, glucagon or dexamethasone on the production of apolipoprotein A-IV in cultured rat hepatocytes. AB - We studied the effects of insulin, glucagon or dexamethasone on the production of apolipoprotein A-IV (apo A-IV) by cultured rat hepatocytes, using specific radioimmunoassay for rat apo A-IV. We also compared the effect of these hormones on the production of apo A-IV with those of albumin and apo A-I, reported previously. In the absence of hormones, apo A-IV and albumin in culture medium increased almost linearly for periods up to 24 h. The rates of accumulation of apo A-IV and albumin in the medium were 15.4 ng/mg cell protein per h and 1.2 micrograms/mg cell protein per h, respectively. The concentration of intracellular apo A-IV remained constant during the incubation. Insulin stimulated the production of albumin, but inhibited the production of apo A-IV dose-dependently. Glucagon inhibited the production of both albumin, and apo A-IV dose-dependently. Dexamethasone showed no significant effects on albumin production, but stimulated apo A-IV production. Thus, apo A-IV production in hepatocytes is regulated by several hormones with different effects on albumin production. The regulatory effects of these hormones on apo A-IV production were almost identical with the effects observed in a course of apo A-I synthesis, suggesting that the production of the two apoproteins are regulated by similar mechanisms. PMID- 1854366 TI - Fat distribution and gender differences in serum lipids in men and women from four European communities. AB - We studied male/female differences in serum lipids in randomly selected 38-year old men (n = 337) and women (n = 342) from various cities in The Netherlands, Sweden, Italy, and Poland. Overall, men had higher triglycerides and total cholesterol levels and lower HDL-levels compared to women (P less than 0.001). Adjustment for smoking habits, city, and body mass index did not remove the gender difference. Further adjustments for waist circumference alone and waist/hip and waist/thigh circumference ratio removed the gender differences in serum triglycerides and total cholesterol. Only adjustment for waist/thigh ratio removed the gender difference in HDL-cholesterol but linear relationships were different in men and women. The average male/female difference in serum lipids, particularly for total and LDL-cholesterol varied considerably among centers. In analyses of the data from the separate centers we found that sex differences in serum triglycerides and HDL-cholesterol in all 4 centers disappeared when adjusted for waist circumference alone and for waist/hip and waist/thigh ratio. For total and LDL-cholesterol, however, adjustment for circumference ratios tended to increase the male/female difference in 2 of the 4 centers. It is concluded that, in European men and women, fat distribution may be responsible for male/female differences in serum triglycerides but that such conclusions are less clear for HDL-, total- and LDL-cholesterol. PMID- 1854367 TI - Formation of a lipid gradient across the human aortic wall during ageing and the development of atherosclerosis. AB - The smooth muscle cell invasion and macrophage stimulation within the intima during prolonged exposure to high blood levels of cholesterol esters contribute to increased production of connective tissue matrix. The thickened intima in turn immobilising more LDL derived lipid from the plasma. With damage to the internal elastic lamellae, from essential hypertension, the absorbed lipid can move down a concentration gradient into the medial tissue. This model was supported by our laboratory finding of a lipid gradient across the aorta wall. The gradient commenced shortly after completion of body growth, when the transmedial gradient became detectable. The slope of the gradient progressively increased during ageing. Association of the lipid medial gradient with the degree of atherosclerotic involvement suggested that the gradient influenced the development of intimal lesions. Accumulation of lipid within the medial tissue may then reduce the inward lipid transfer rate from the intima, promoting increased intimal retention and cause the formation of atherosclerotic plaques from the fat saturated intima. PMID- 1854368 TI - Diet-induced alteration in the activity of plasma lipid transfer protein in normolipidemic human subjects. AB - Studies were performed to investigate the effect of diets rich in oleic or linoleic acids on the activity of plasma cholesteryl ester transfer protein (CETP) in normolipidemic subjects. Previous to the test diets, all subjects consumed a baseline diet rich in saturated fatty acids ("sat-diet") for 17 days. The test diets, rich in either monounsaturated fatty acids ("mono-diet") or rich in polyunsaturated fatty acids ("poly-diet"), were given for 5 weeks to 52 normolipidemic healthy volunteers. The activity of CETP was measured, using a method independent of endogenous plasma lipoproteins, as the rate of exchange of radioactive cholesteryl oleate between labelled LDL and unlabelled HDL. The "mono diet" induced a statistically significant decrease in CETP activity (from 115 +/- 20 to 102 +/- 19 units/ml plasma, P less than 0.01), while the small decrease on the "poly-diet" (from 111 +/- 23 to 107 +/- 22 units/ml plasma) did not reach significancy. The percentual decrease in CETP activity induced by the "mono-diet" was higher than that induced by the "poly-diet" as was also found for the decrease in LDL cholesterol. In both diet groups a positive correlation was found between changes in CETP activity and changes in plasma total or (VLDL + LDL) cholesterol. The results suggest that high levels of dietary monounsaturated fatty acids may result in decreased plasma CETP activity, as well as LDL cholesterol levels. The mechanisms of these effects, and their possible interrelations, remain to be established. PMID- 1854369 TI - Models of arterial aneurysm: for the investigation of pathogenesis and pharmacotherapy--a review. AB - Arterial aneurysms continue to provide a clinical challenge for neurosurgeons and vascular surgeons. Many different animal models have been developed in which the pathogenesis, growth, rupture and treatment of these aneurysms can be investigated. These animal models have been reviewed here, with the focus on saccular aneurysms in the muscular cerebral arteries and fusiform aneurysms in the elastic aorta. Consideration of the animal models described indicates appropriate experimental models and new directions for the development of improved models in which to test the effects of pharmacologic factors in limiting the growth and rupture of aneurysms. PMID- 1854370 TI - Bone collagen, mineral and trace element composition, histomorphometry and urinary hydroxyproline excretion in chronically-treated alcohol-fed rats. AB - (1) We examined the possibility that enhanced fragility of the bony skeleton in alcohol abusers may be a consequence of a reduction in collagen composition. Male rats were fed a liquid diet containing 36% of total calories as ethanol; controls were pair-fed iso-caloric glucose. At 3, 7 and 14 days of treatment, collagen contents of tibia were unaltered, but small and significant reductions (15-30%) were observed at 28 and 42 days of treatment. Urinary hydroxyproline excretion was increased by 40-60% at 42 days of treatment, suggesting enhanced collagen degradation. (2) Bones of rats treated with ethanol for 42 days had significantly reduced mineral content (approximately 20%) with accompanying reductions in phosphate, calcium, copper and magnesium, but not sodium or potassium. Water content was unaltered, but tibial zinc and iron were increased by approximately 15%. (3) Histomorphometric analysis of bones taken at 42 days showed significant reductions in cortical bone thickness of lower tibia (by 28%). The thickness of the upper cortices and cancellous bone of the tibia was unaffected. Reductions in trabecular bone volume (approx. 25%) did not achieve statistical significance. (4) These observations are consistent with the known enhanced fragility of bones in alcoholic rats. The regional susceptibility of the tibia may be related to reduced load bearing as a result of muscle atrophy. PMID- 1854371 TI - Pituitary gonadal functioning in male alcoholics in an Indian psychiatric hospital. AB - Serum levels of luteinizing hormone (LH), testosterone and hepatic functions were measured in 38 male alcoholics and in 24 male control subjects. Significant elevation of serum LH and a trend of low serum testosterone were noted with scant evidence of advanced liver disease. None of the alcoholics had clinical stigmata of hypogonadism and feminization. PMID- 1854372 TI - A century of alcoholism conferences: unchanging themes. AB - Modern conferences on alcoholism receive research papers and stimulate multidisciplinary discussion, but this is not new, similar events took place 100 years ago. The published proceedings of Chester's conference of 1895 are reviewed and compared with recent conferences. Subjects then included alcohol's effect on the foetus, particular facets of women's drinking and increased availability in grocer's shops, the young and evaluation of educational programmes, alcohol in the workplace, long term control studies on alcoholics, laboratory studies on reaction time, attitude of the popular press, effects of restrictions in outlets and hours and lessons to be learnt from such in Scotland, and political and legislative remedies including evidence from Scandinavia. A full knowledge of earlier research and experience may modify current thinking and prevent simple repetition of previous endeavour. PMID- 1854373 TI - The effect of fructose on alcohol metabolism and on the [lactate]/[pyruvate] ratio in man. AB - Ten male subjects were given alcohol by intravenous infusion and maintained at a constant blood alcohol level. The rate of alcohol metabolism was measured before and after an oral dose of fructose (100 g), as the amount of alcohol required to maintain the steady state. The mean rate of alcohol metabolism increased by 80% after fructose but there was considerable variation among the subjects, which was related to their plasma fructose concentrations. Blood lactate increased after fructose to a greater degree than blood pyruvate, resulting in a significant increase in [lactate]/[pyruvate] ratio. Since fructose increased the [lactate]/[pyruvate] ratio when it increased alcohol metabolism, the action of fructose cannot be explained by a decrease in the liver cytoplasmic [NADH]/[NAD] ratio and some other mechanism must be sought. PMID- 1854374 TI - Does alcohol modify responses to reward in a competitive task? AB - Alcohol in two doses (0.75g/kg and 0.25/kg) and a placebo were administered to three matched groups of subjects. Subjective ratings and breath alcohol levels were completed pre-intake and at 30 min intervals up to 2 hr after intake. At 1 hr post-intake, the subjects took part in a competitive task with increasing rewards during which cardiac and electrodermal activity were monitored. Alcohol had very little effect. It did not affect the level of reward administered nor the physiological parameters measured. The only mood effect was sedation. There was no evidence of tension reduction or response disinhibition. PMID- 1854375 TI - The effects of alcohol and other drugs on psychomotor performance and cognitive function. AB - The effects of four doses of alcohol (0.25 g/kg-1 g/kg) and placebo on a standard test battery of cognitive and psychomotor performance are described. The tests included critical flicker fusion threshold, choice reaction time, tracking and memory scanning. The results of this experiment are compared with those of a number of similar studies which examined the effects of other psychoactive substances. Using relative effect sizes, the behavioural toxicity of alcohol is compared with the effects of these other drugs on psychomotor performance and cognitive function. PMID- 1854376 TI - A three-sample test of a masked alcohol screening questionnaire. AB - The study tested an expanded version of a masked alcohol screening instrument developed by Wallace and Haines [Use of a questionnaire in general practice to increase recognition of patients with excessive alcohol consumption. British Medical Journal 290, 1949-1953 (1985)]. The alcohol subscales include the CAGE, consumption, trauma, medical advice, past problems, and present problems with alcohol. There is preliminary evidence of the construct validity and reliability of the Health Screening Survey (HSS). As expected the HSS was sensitive in known populations of alcoholics (0.96; 0.95) correctly identifying at least 95% of the alcoholic patients recruited from two treatment centers. Specificity was adequate with identified nonalcoholics (0.80; 0.70). It was also sensitive in a community primary care sample, correctly classifying 78% of the subjects meeting DSM-III criteria for alcohol abuse and/or dependence. There were gender differences in the validity of the subscales in the community sample with alcoholic males more likely to report problems on the questionnaire than alcoholic females. Based on results, the HSS was revised to improve validity. PMID- 1854377 TI - Alcohol consumption in young adults in the rural communities of Spain. AB - In the spring of 1987, the patterns of alcohol consumption in 1,886 young people (14-30 years old) from the rural communities (less than 10,000 inhabitants) of Castile and Leon (Spain) were analysed. 64.1% of the young adults took alcoholic drinks at least once a week, while 24.4% were 'daily' consumers. Beer (56%) was the preferred drink, followed by gin (22.4%) and wine (21.3%). The age of starting to drink was close to 16 years old and the alcohol intake per capita was 19 g/day. Both frequency and intake were higher among males and at weekends. The main reported reason for drinking was 'because I like its taste' (39.1%). The results confirm the common consumption of alcoholic drinks among Spanish young adults, the establishment of beer as the preferred drink and the more extensive consumption of alcohol by males and at weekends. PMID- 1854378 TI - [Biology of the human immunodeficiency virus: a review]. AB - The human immunodeficiency virus (HIV) a retrovirus responsible for the condition known as AIDS is presented from its biologic perspective. The viral structure and its relation to the pathogenesis of the infection is described. The course of the cellular infection is described and its relation to the manifestation of disease. The technology for detection of viral infection is described and the importance of seropositivity. The manifestations are described in relation to the virus as well as the possible intervention. There is still no alternative but education. PMID- 1854379 TI - Career choice and professional trajectory of Fifth Pathway students. AB - We have studied the professional trajectory of 177 participants of the Fifth Pathway Program of the University of Puerto Rico School of Medicine between July 1973 and June 1987. Eighty six per cent of the students were Puerto Rican. Sixty seven per cent had studied in the Universidad Autonoma de Guadalajara. Ninety seven per cen of the respondents specialized and 39 per cent subspecialized; sixty nine per cent selected primary care specialties. Eighty three per cent of the fifth pathway participants are licensed to practice medicine in Puerto Rico and 37% are licensed to practice in one or more of 21 states of the Nation. Twenty one per cent held academic positions and 11.4 per cent were department chairpersons or chiefs of sections. The professional trajectory of Fifth Pathway participants is similar to that of medical graduates of the University of Puerto Rico School of Medicine. PMID- 1854380 TI - The Raffucci forum and honor lecture--10 years later. PMID- 1854381 TI - Surgical education--a dinosaur in the medical education closet. PMID- 1854382 TI - Ultratrace minerals mythical elixirs or nutrients of concern? AB - Demonstration of the nutritional significance of the ultratrace elements has resulted from studies indicating enhanced need in organisms exposed to various metabolic, hormonal, physiological and nutritional stresses. These studies indicate that some ultratrace elements, namely boron and silicon, will be found to be nutritionally important. The dietary lack of these elements may result in suboptimal function and composition of bone and brain. PMID- 1854383 TI - Carnitine and lipid metabolism. AB - Carnitine, a short-chain nitrogen containing carboxylic acid, is found in meat and dairy foods. Carnitine aids in a shuttle process that makes long-chain, fatty acid coenzyme A derivatives available for B-oxidation. Normal healthy adults have adequate carnitine stores and do not require dietary carnitine. However, neonates, chronically and critically ill patients with decreased muscle and liver carnitine store seem to benefit from carnitine supplementation to enhance their tolerance of metabolic stress. PMID- 1854384 TI - [Post-mortem cesarean sections in Puerto Rico, 1805-1807]. AB - The idea of saving an infant by incising the abdomen of the recently deceased mother was first put into practice in ancient times, and the Catholic Church endorsed its use to provide baptism for the infant's soul. The practice received official support in Madrid in 1804 with a Real Cedula (royal order) of Charles IV to the civilian and ecclesiastic officials of the Indies and the Philippines. This operation was used, before the cedula, in Spain, Mexico, Venezuela and Peru, but in Puerto Rico this order seems to have provoked the practice of post-mortem caesarean section. In a review of burial records of the San Juan cathedral for 1797 to 1814, one such operation is mentioned (1807), but the records of Cayey (a town in the mountains) from 1801 to 1812 show three cases (1805-6). We transcribe here (with modern spelling) the cedula and burial certificates, and we then comment on their significance. PMID- 1854385 TI - Prevalence of the microbiologic flora in contact lens wearers at the Puerto Rico Medical Center. AB - The prevalence of microbioogic flora was determined in a convenience sample of contact lens wearers at the Puerto Rico Medical Center, ophthalmology clinics obtaining cultures from the conjunctival fornices. Gram positive bacterial prevalence was 100% in the control group, as well as in rigid gas permeable lens wearers. In the soft contact lens group, gram positive bacterial prevalence was 94.7%. On the other hand prevalence of Gram negative bacteria is null in the soft contact lens wearer population, being only 2.5% in control group, and 45.5% for Rigid Gas Permeable wearers. These contact lens wearers were using different disinfection systems. PMID- 1854386 TI - Pacemaker atrial lead dislodgement and malposition inducing ventricular pacing. AB - Pacemaker atrial lead dislodgement inducing ventricular pacing is reviewed, and four such observed cases are described. This interesting complication of the atrial lead producing ventricular depolarization results in an array of electrocardiographic manifestations and vignettes. These documented experiences emphasize the infrequent persistence of this event, even with the utilization of modern atrial passive and active fixation leads. PMID- 1854387 TI - Bittering agents in the prevention of accidental poisoning: children's reactions to denatonium benzoate (Bitrex). AB - The responses of young children to Denatonium Benzoate (Bitrex) were observed, in order to assess the potential of this bittering agent in the prevention of accidental poisoning. Thirty-three children aged 17-36 months were offered orange juice containing Bitrex (in a concentration of 10 parts per million). Of the 30 children who took some of this juice, only seven were willing to take more than 10 gm. A variety of negative verbal and non-verbal responses were noted. It is suggested that the highly unpalatable nature of Bitrex makes this compound a useful additive that could well prevent accidental poisoning from household products of mild to moderate toxicity. PMID- 1854388 TI - A review of 7 years of complaints in an inner-city accident and emergency department. AB - In 7 years between 1982-88, 122 complaints were lodged against the Accident and Emergency department of King's College Hospital. A high percentage mentioned more than one aspect per complaint. Commonest were those regarding attitude (37.7%), missed diagnosis (36.6%), waiting time (32.8%), cursory examination (14.7%) and poor communication (11.5%). These causes of complaint are amenable to improvement. Training in interpersonal skills may reduce complaints of attitude. A high index of suspicion for the unusual and careful examination of patients would reduce complaints of missed diagnosis. Sufficient medical and nursing staff would reduce waiting time and improvements in communication with patients would keep this aspect to a minimum. Complaint investigation can be time consuming, when dissatisfaction is expressed explanations at the time of presentation by senior staff members may head-off a formal complaint. PMID- 1854389 TI - Minor procedures in the accident and emergency department: can Entonox help? AB - The efficacy of Entonox as a supplement to local anaesthesia for minor surgical procedures was studied. Eighty-five patients undergoing surgery for the incision and drainage of a subcutaneous abscess using a local anaesthetic were involved in a trial to ascertain the level of pain associated with such procedures and to investigate the possibility of using on-demand Entonox to supplement the local anaesthesia provided. Patients received either the standard local anaesthesia, or, alternatively, the local anaesthesia was supplemented with oxygen or Entonox via on-demand apparatus. Patients indicated on three linear visual analogue scales their pain, anxiety and total discomfort, and also on a cartoon pain rating scale, at different stages during the operation. Results showed that there was no statistically significant reduction in pain provided by the Entonox, despite general patient approval. Both oxygen and Entonox showed some anxiolytic properties. Pure oxygen was also seen to produce a rise in heart rate, while both gases (pure oxygen and Entonox) caused an increase in diastolic blood pressure. It was also seen that the patient's short term memory of the pain experienced was unaffected by pure oxygen or Entonox. PMID- 1854390 TI - Which dogs bite? AB - Young children (less than 11 years old) are a particular risk group for dog bites. Dog bites commonly occur from the family pet. Alsatian or alsatian mixes are the biggest group in the study causing dog bites. Alsations are a popular breed. By comparison Retrievers (Labrador and Golden), also a popular breed, caused few bites. PMID- 1854391 TI - A review of radiological abnormalities in 135 patients presenting with acute asthma. AB - Six hundred and ninety-five attendances were made to the Accident and Emergency Department of a district general hospital over a 6-month period by patients with acute asthma. On hundred and thirty-five chest radiographs were performed, and the radiologists' reports analysed. Nineteen abnormalities were reported (14%) which may have altered the management of the patient. It is recommended that chest radiographs be considered in patients who do not rapidly respond to initial therapy. PMID- 1854392 TI - Do patients presenting to accident and emergency departments have low serum anticonvulsant concentrations? AB - It is often felt that poorly controlled epileptic patients, who are taking anticonvulsant medication, are over represented in A&E departments compared to the general population. This A&E based study set out to determine whether such patients do have inadequate serum anticonvulsant levels, when they present following a seizure, to A&E departments. All epileptic patients, taking medication, who presented to the A&E departments of St. Bartholomew's and Hackney Hospitals, London, over a 4-month period were studied. Serum anticonvulsant concentrations were measured on their arrival in the departments. Forty-six patients were studied. Only 21% of anticonvulsant drug concentrations were within 'therapeutic' ranges. A total of 66% were below 'therapeutic' ranges and 13% were potentially toxic. The implication of these findings is discussed. PMID- 1854393 TI - Hip dislocations in chronic osteomyelitis. AB - We present two cases of spontaneous dislocation of the hip joint due to chronic osteomyelitis of the upper femur. Spontaneous hip dislocations occur in certain pathological conditions such as poliomyelitis (Ingram, 1980), cerebral palsy (Howard et al., 1985), osteomyelitis and neurofibromatosis. PMID- 1854394 TI - Pulmonary embolism in patients attending the accident and emergency department with pleuritic chest pain. AB - A series of 92 patients presenting to an accident and emergency department with pleuritic chest pain is described. Only one of the patients had a diagnosis of pulmonary embolus. All the patients were followed up over a period of 3 months. During this time none of them suffered from mortality or morbidity which could be related to pulmonary embolism. No evidence was obtained during this study that a more aggressive approach to such patients is required in order to achieve the diagnosis. PMID- 1854395 TI - Baby walker related injuries--a continuing problem. AB - Baby walkers have been associated with burns, head trauma and other types of injury. A retrospective study of all infants under the age of two years attending an accident and emergency unit demonstrated 22 injuries associated with baby walkers from a total of 1049 attendances. The most serious injuries were three skull fractures, with the most common mechanism being of a fall downstairs in the walker. Injury while in a baby walker occurred with a similar frequency to injury due to road traffic accidents. We conclude that despite previous warnings Baby Walkers still represent a considerable hazard to infants. PMID- 1854396 TI - Anterior dislocation of the restrained shoulder: a seat-belt injury. AB - The reduction in morbidity and mortality since the enforcement of seat-belt usage is well documented. Complications from the belt are also reported and the authors present anterior dislocation of the restrained shoulder, an injury not previously described. The mechanism of injury is explained and a change to the present standard of restraints is suggested. PMID- 1854397 TI - The need for ventilation holes in children's dummies. AB - A 2-year-old child was brought into the Accident Department with a history that he had swallowed his dummy. There were no direct witnesses to the injury. The child had come up to its mother salivating and pointing to its mouth. The initial incident happened approximately 20 min prior to presentation at the Accident Department after a 999 call. Attempts at digital removal of the dummy by ambulancemen had failed. The child was pink and quiet but responding to commands and cooperative. He had a small abrasion to his forehead presumably due to his initial fall when his dummy was forced into his mouth. The teat of the dummy was clearly visible in the pharynx. The child was able to breathe by virtue of the two air holes in the flange piece of the dummy. PMID- 1854398 TI - A chicken bone in the rectum. AB - A case of an ingested chicken bone lodging in the anal canal is described which presented as severe rectal pain. Certain people are at increased risk of foreign body ingestion, in particular denture wearers. The foreign body is usually obvious and easily removed and although the risks of perforation are not high it is important to exclude it by proctosigmoidoscopy following removal of the foreign body. PMID- 1854399 TI - Intraosseus needles. PMID- 1854400 TI - The hanging head method for the treatment of acute wry neck. PMID- 1854401 TI - Acyclic nucleoside and nucleotide analogues: a new class of antivirals. PMID- 1854402 TI - Antitumor imidazotetrazinones: prodrugs targeted to the major groove of DNA. PMID- 1854403 TI - Adenosine derivatives as agonists of adenosine receptors. PMID- 1854404 TI - Imidazolyl derivatives in medicinal chemistry. PMID- 1854405 TI - 2-Amino phenylhydrazine derivatives in the synthesis of heterocyclic compounds of pharmacological interest. PMID- 1854406 TI - Nonpsychotropic synthetic cannabinoids as therapeutic agents. PMID- 1854407 TI - Nursing, then and now. PMID- 1854408 TI - Lyme disease update. PMID- 1854409 TI - Teaching early breast cancer detection strategies. AB - Breast cancer is the most common cancer occurring among women. Currently, breast cancer can be detected early and treated effectively if all asymptomatic women participate in the screening program. Screening strategies include a mammogram, medical examination of the breast, and breast self-examination. This article describes the nurse's role in promoting and decreasing barriers to these strategies for early detection of breast cancer. PMID- 1854410 TI - Nursing intervention with the family of the critically ill patient. Videotape: an option for family orientation to the critical care unit. AB - It is important for the critical care nurse to consider the family of the patient in all phases of care to the individual within the critical care setting. The family's structure and usual patterns of functioning will be significantly altered by the illness of one member. By using an "Orientation to the Critical Care Unit" program for the family as well as the impact variables involved, the nurse is better able to assist the family cope with the situation within. (This video orientation program was implemented at a hospital in Northeastern Ohio in 1988 and is currently being shown to families of critical care patients. Feedback from nursing staff and family members has proven to be very positive. PMID- 1854411 TI - Innovative clinical teaching. AB - Participating faculty are entering their third year using this type of student rotation and have found that it continues to be a positive teaching-learning experience for faculty, staff, and students. It has enabled a greater number of students to enjoy a positive clinical experience in areas that previously were limited to a smaller number of students. Perhaps this strategy, or a part of it, may be of benefit to other nurse educators as a method of improving undergraduate clinical experiences. PMID- 1854413 TI - Industrial rehabilitation of mentally ill patients--Soviet perspective. PMID- 1854412 TI - Grand rounds for SNs and RNs. AB - The use of Nursing Grand Rounds as a teaching tool helps students gain clinical competence and become more proficient in nursing processes. Adaptation of this learning tool for staff development could be an important strategy for personal and professional growth of nurses in gerontological settings. PMID- 1854414 TI - Receipts. PMID- 1854415 TI - Reducing the pain of intramuscular (IM) injections. AB - The rate of administration of the drug may be a factor in pain from the injection site. This information, as well as other techniques to reduce the pain of IM injections, is presented. PMID- 1854416 TI - The energy of love. As nurses, we see miracles all around us. PMID- 1854417 TI - Estrogen replacement therapy. AB - In summary, oral estrogens are often prescribed to relieve menopause symptoms. They should not be used in women who have had breast cancer, thrombophlebitis, hypertension, gallstones, or undiagnosed abnormal genital bleeding. Hormone replacement therapy has proven to be very useful in preventing osteoporosis, hot flashes, night sweats, and vaginal dryness. More information is needed before they should be recommended for the prevention of heart disease in postmenopausal women. PMID- 1854418 TI - The history of nursing and politics in the United States. PMID- 1854419 TI - Honoring elders: empowering caregivers. Student Nurse Day. Community College of Philadelphia. PMID- 1854420 TI - The use of carbamazepine to treat benzodiazepine withdrawal in a geriatric population. AB - Rapid withdrawal of short to intermediate half-life benzodiazepines may be hazardous, particularly in the elderly. The use of carbamazepine to facilitate withdrawal has been reported in younger patients. We describe four elderly patients (average age, 72.5 years) who had each experienced at least one unsuccessful attempt at alprazolam withdrawal and who were subsequently successfully withdrawn via the use of carbamazepine over a period ranging from 2 to 6 days. These geriatric patients experienced no major withdrawal symptoms, but mild symptoms were common. There was no correlation between dose or duration of alprazolam use and extent of withdrawal symptoms. We recommend use of this treatment regimen in a hospital setting only, where close monitoring can occur. PMID- 1854422 TI - Hydergine in Alzheimer's disease. PMID- 1854421 TI - Adult dementia due to intraneuronal accumulation of ceroidlipofuscinosis (Kufs' disease): ultrastructural study of two cases. AB - Two cases, a man and a woman, presented the initial signs of progressive dementia at about age 40 years. Aphasia, facial dyskinesias, and ataxia were associated with behavioral disturbances in the first patient. Aphasia, oculomotor disturbances, and ataxia coexisted with dementia in the second patient. In both cases, ultrastructural examination of a cerebral biopsy showed intraneuronal granular osmiophilic deposits mixed with lamellar structures and fingerprint profiles. Such deposits are characteristic of Kufs' disease. In the first patient, brain autopsy was performed 3 years after cerebral biopsy. Our two cases presenting dementia with motor disturbances correspond to type B Kufs' disease. PMID- 1854423 TI - Response to treatment of depression in the old and very old. AB - Treatment responses were monitored in 101 depressed patients, ranging in age from 64 to 92 years, hospitalized on a geropsychiatry unit. Forty-six percent of the patients received ECT. Medications were used in the majority of patients. Responses were assessed with both depression inventories (Beck Depression Inventory and Geriatric Depression Scale) and physician-rated global improvement scores. Advanced age was not associated with poor outcome. ECT was the most important variable associated with a good response, regardless of age. PMID- 1854424 TI - Psychiatric symptoms in cases of clinically diagnosed Alzheimer's disease. AB - All incident cases of clinically diagnosed Alzheimer's disease were identified through the unique record linkage system of the Mayo Clinic. Thirty-nine (32%) of the sample of 122 had a psychiatric history that preceded the onset of CDAD by at least 3 years. Twenty-five percent of the study population had had an episode of delirium within 2 years of the onset of CDAD. Eighty-four percent of the cases had psychiatric symptoms in the course of CDAD that were documented in their medical records. Specific symptom patterns included agitation, combativeness, confusion and disorientation, depression, psychosis, and wandering. These symptoms occurred more frequently in clusters than singularly. PMID- 1854425 TI - Tardive dyskinesia in Alzheimer's disease: clinical features and neuropathologic correlates. AB - Medical record review was conducted on 14 patients with neuropathologically confirmed Alzheimer's disease, all of whom had been treated with antipsychotic medications, to determine the relationship between neuropathology and the development of tardive dyskinesia. Four cases were found to have chart descriptions of hyperkinetic movement disorders consistent with tardive dyskinesia. When the group with tardive dyskinesia was compared to the group without tardive dyskinesia, there were no statistically significant differences regarding gender, age of onset of dementia, duration of dementia, age at death, or duration of antipsychotic treatment. Neuropathologic comparisons revealed greater degenerative changes in the substantia nigra in those patients with tardive dyskinesia. These preliminary observations suggest that patients with Alzheimer's disease and significant coexisting substantia nigra pathologic changes may be at higher risk for developing tardive dyskinesia when treated with antipsychotic medication. PMID- 1854426 TI - Differential diagnosis of dementia: intra- and interdiscipline agreement. AB - Ninety clinicians from six disciplines diagnosed ten case descriptions of patients, judged by a multidisciplinary expert committee to suffer from dementia. Five cases were diagnosed before and five after a consensus meeting on the diagnosis of dementia. A significant change in the level of agreement between the disciplines could not be established. The analysis did show a significant difference between the disciplines in the use of etiologic diagnoses. The results indicated that, in order to avoid possible bias caused by medical specialization, a multidisciplinary approach for this type of patient is recommended. PMID- 1854427 TI - Geriatric epilepsy: a review. AB - After the turn of the century, the proportion of population over 60 years of age is expected to be over 20%. Recent epidemiologic studies show a higher incidence of new-onset epilepsy in the population over 60 years of age compared with preceding decades of life. The predominant seizure type in up to 80% of these new cases of epilepsy is simple and complex partial manifestation. This paper reviews the literature documenting the increased incidence of partial seizures in the aging population, explores the known etiologies of new-onset epilepsy, and uses five case vignettes presenting with complex partial symptomatology. PMID- 1854428 TI - Cellular interactions in asthma. AB - Immediate phase of asthma is induced by mast cells. Late phase asthmatic response is related to other cells such as, macrophages, lymphocytes, eosinophils, and could pass to chronicity and is usually associated with bronchial hyperreactivity. Pathological or functional studies of the different cells involved, could be done in peripheral blood, broncho-alveolar lavage, bronchial biopsies or nasal lavages. PMID- 1854429 TI - Nocturnal asthma: a model of chronobiologic and pathophysiologic interactions. AB - Nocturnal asthma is an important component of asthma, which affects more than 90% of asthmatics. It has a relationship with morbidity and mortality in 70% of cases. The most vulnerable period is between 10 p.m. and 7 a.m., with a peak at 4 a.m. Nocturnal asthma undoubtedly creates a consideration of many complex factors, of which some are circadian. PMID- 1854430 TI - [Specific immunotherapy using Alpha-Fraction-Retard-D. pteronyssinus. Double blind study in asthma]. AB - A multicenter, double blind clinical study on two homogeneous, treated and untreated groups, has allowed an objective appreciation of the results of specific immunotherapy using the alpha-fraction of D. pteronyssinus in asthma. A statistically significant difference was seen of the consumption of drugs in the treated group and in infants of less than 5 years (p = 0.047). Tolerance, evaluated as a function of local and secondary effects was excellent and comparable in the two groups. PMID- 1854431 TI - Biochemical activities of entomophagous fungi. AB - This review is directed toward the study of the physiology and biochemistry of parasitic fungi on insects and stresses the usefulness and utility of these organisms from the standpoint of applied research and biotechnology. The review covers the principal contributions made by investigators toward elucidation of the infective mechanisms of the entomogenous fungi, and the various biochemical attributes of these organisms. The interplay of the various enzymes and associated biochemical substances which are involved in the infective process is discussed as well as the important studies of the peculiar physiology frequently associated with these microorganisms. PMID- 1854432 TI - Enterococci in milk and milk products. AB - Enterococci are widely distributed in nature. They gain entry into milk and milk products through the water supply, equipment, and insanitary and unhygienic conditions of production and handling. They have been incriminated as direct or indirect agents of disease. The evidence concerning their involvement is only circumstantial. These reports are also disputed as the disease symptoms have not been experimentally induced in animal models. However, there is sufficient evidence to indicate that prolific growth of enterococci in foods may lead to formation of clinically significant levels of pressor amines. These amines are very thermostable and therefore remain active even after heat processing, which eliminates all viable streptococci. These pressor amines may be involved in the onset of migraine attacks and produce hypersensitive crises in psychiatric patients who are being treated with monoamine oxidase inhibitors for depression. PMID- 1854433 TI - Interfaces of the yeast killer phenomenon. AB - A new prophylactic and therapeutic antimicrobial strategy based on a specific physiological target that is effectively used by killer yeasts in their natural ecological competition is theorized. The natural system exploited is the yeast killer phenomenon previously adopted as an epidemiological marker for intraspecific differentiation of opportunistic yeasts, hyphomycetes, and bacteria. Pathogenic microorganisms (Candida albicans) may be susceptible to the activity of yeast killer toxins due to the presence of specific cell wall receptors. On the basis of the idiotypic network, we report that antiidiotypic antibodies, produced against a monoclonal antibody bearing the receptor-like idiotype, are in vivo protecting animals immunized through idiotypic vaccination and in vitro mimicking the antimicrobial activity of yeast killer toxins, thus acting as antibiotics. PMID- 1854434 TI - Beyond water activity: recent advances based on an alternative approach to the assessment of food quality and safety. AB - Water, the most abundant constituent of natural foods, is a ubiquitous plasticizer of most natural and fabricated food ingredients and products. Many of the new concepts and developments in modern food science and technology revolve around the role of water, and its manipulation, in food manufacturing, processing, and preservation. This article reviews the effects of water, as a near-universal solvent and plasticizer, on the behavior of polymeric (as well as oligomeric and monomeric) food materials and systems, with emphasis on the impact of water content (in terms of increasing system mobility and eventual water "availability") on food quality, safety, stability, and technological performance. This review describes a new perspective on moisture management, an old and established discipline now evolving to a theoretical basis of fundamental structure-property principles from the field of synthetic polymer science, including the innovative concepts of "water dynamics" and "glass dynamics". These integrated concepts focus on the non-equilibrium nature of all "real world" food products and processes, and stress the importance to successful moisture management of the maintenance of food systems in kinetically metastable, dynamically constrained glassy states rather than equilibrium thermodynamic phases. The understanding derived from this "food polymer science" approach to water relationships in foods has led to new insights and advances beyond the limited applicability of traditional concepts involving water activity. This article is neither a conventional nor comprehensive review of water activity, but rather a critical overview that presents and discusses current, usable information on moisture management theory, research, and practice applicable to food systems covering the broadest ranges of moisture content and processing/storage temperature conditions. PMID- 1854435 TI - Hydrolysis kinetics of 1,3-benzoxazine-2,4-dione (a potential salicylamide prodrug) and various N-substituted derivatives. AB - The kinetics and mechanism of hydrolysis of 1,3-benzoxazine-2,4-dione and its N methyl and N-benzoyl derivatives were studied in aqueous solution to provide basic information on the reactivity of the benzoxazinedione structure and to assess the potential of unsubstituted 1,3-benzoxazine-2,4-dione as a prodrug for salicylamide. The compounds were found to hydrolyze quantitatively to the parent salicylamide. The pH-rate profiles obtained at pH 1-11 were accounted for by a spontaneous or water-catalyzed reaction which predominated at pH 1-4 and a hydroxide ion-catalyzed reaction. The rates of hydrolysis were catalyzed slightly in the presence of human plasma and rat liver homogenate, the exception being the N-benzoyl derivative which was hydrolyzed very fast in plasma solutions to N benzoylsalicylamide. The aqueous solubility and lipophilicity characteristics of 1,3-benzoxazine-2,4-dione were determined. The results obtained suggest that the latter may function as a prodrug for salicylamide with the potential of depressing the extensive first-pass metabolism of salicylamide following oral or rectal administration. PMID- 1854436 TI - Synthesis and antiinflammatory activity of indole carboxylic acids and esters. AB - 1-Phenylalkylindole-3-carboxylic acids 1-4, indole-1-acetic acids/esters 5-10 and the hydrazones 11-15 were prepared and submitted to the rat paw edema test using carrageenin. In the first two groups of compounds, the 2-chloro indoles were more active than the corresponding indole derivatives. In the third group the activity seemed to be determined largely by the substituent at the 1-position. PMID- 1854437 TI - Prodrugs of cimetidine with increased lipophilicity: N-acyloxymethyl and N alkoxycarbonyl derivatives. AB - Bioreversible derivatization of cimetidine to afford more lipophilic prodrugs was performed by N-acyloxymethylation of its imidazole group as well as by N acylation with various chloroformates. Both the N-acyloxymethyl and N alkoxycarbonyl derivatives were readily hydrolyzed to cimetidine in human plasma and in rat liver homogenate. The pH-rate profiles for the hydrolysis of the derivatives were derived at 60 degrees C. The derivatives were all more lipophilic than the parent drug as determined by partition experiments in octanol aqueous buffer systems. In vitro studies using the modified Ussing-chamber technique showed that some derivatives possessed increased permeability coefficients for the transport across the rat jejunum relative to cimetidine. The results obtained suggest that these derivatives may be useful to improve the biomembrane transport characteristics of the hydrophilic cimetidine. PMID- 1854438 TI - Inhibition of mitochondrial respiratory chain by alkylthiolated 2,3-dicyano-1,4 benzoquinones. AB - A series of alkylthiolated 2,3-dicyano-1,4-benzoquinones was synthesized and tested for the effects on the respiratory chain in beef heart mitochondria as an antimetabolite of ubiquinones (coenzyme Q). It was proved that these analogs are among the best inhibitors of both succinate oxidase and NADH oxidase systems. The introduction of a 2,3-dicyano group to the quinone ring was found to be more favorable for inhibitory activity than 2,3-dimethoxy, 2,3-dimethyl groups and bicyclic quinones such as 2,3-ethylenedioxy-1,4-benzoquinones and 1,4 naphthoquinones. The inhibitory activity was minimally sensitive to the length of the alkylthio side-chain. On the other hand, the difference spectra of reduced minus oxidized forms of cytochromes were investigated to identify the inhibitory site, suggesting that alkylthiolated 2,3-dicyano-1,4-benzoquinones inhibit at sites between the substrates (succinate and NADH) and cytochrome b, and at the site after cytochrome a + a3 in the respiratory chain. PMID- 1854439 TI - Solution of a Fab (26-10)/digoxin complex by generalized molecular replacement. AB - The structures of a Fab fragment of a monoclonal murine antidigoxin antibody (26 10) complexed with digoxin and of a mutant of the Fab itself have been solved by molecular replacement. The solution strategy employed a generalization of molecular replacement. Prior to translation searches, a large number of the highest rotation-function peaks were subjected to a rigid-body refinement against the linear correlation coefficient between intensities of observed and calculated structure factors in which first the overall orientation of the model and then the orientations and translations of the individual domains (VH, VL, CH1 and CL) were refined. This procedure clearly identified the correct orientation of the search model. Furthermore, it produced a significant and unambiguous solution for the translation search. After rigid-body refinement, the R factor was in the low forties at 8-2.5 and 8-2.7 A resolution for the Fab mutant and the Fab/digoxin complex, respectively. One round of simulated annealing refinement of all atomic positions reduced the R factor to the low twenties in both cases. PMID- 1854440 TI - Ab initio phase determination for X-ray diffraction data from crystals of a native protein. AB - An efficient algorithm for the determination of an everywhere positive electron density distribution that agrees with observed structure amplitudes has been used to determine the phases of X-ray diffraction data from recombinant bovine chymosin, a protein with 323 amino-acid residues in the molecular chain whose structure was recently determined using molecular replacement methods. A systematic procedure for testing the signs of centric reflections, using the total entropy of the map as a figure of merit, was used to produce a low resolution map. The phases of acentric and additional centric reflections were then chosen by adding them to the map with various possible phases and computing the total entropy of the resulting map. Of 159 centric reflections whose phases were chosen by this procedure, 141 had the same phase as in the refined structure. The median absolute phase difference for 1811 acentric reflections was 32 degrees. A map produced from these 1970 reflections, out of 12,346 reflections in the data set, showed a remarkable agreement with the refined structure. This molecule is many times larger than any whose structures have previously been determined without the use of isomorphous replacement, molecular replacement or anomalous dispersion, and the map demonstrates the potential of maximum-entropy methods in macromolecular structure determination. PMID- 1854441 TI - Acid-abrasive enamel reduction for tooth color correction. AB - The purpose of this article is to present an acid-abrasion ("enamel microabrasion") technique which can eliminate superficial enamel discoloration. The technique provides a conservative alternative for some patients who might otherwise have received porcelain or composite resin veneer restorations. PMID- 1854442 TI - Root caries: some facts and treatment methods. AB - It has been projected that by the year 2000 every fifth person in the United States will be 65 or older, and root caries will create special restorative needs for this population. This article discusses the characteristics of root caries, the clinical conditions that should be anticipated in diagnosing it, their histologic and bacteriologic aspects, the misleading factors in radiographic diagnosis, the specific and general treatment concepts, the advantages and disadvantages of the popular restorative materials, and the principles applied in specific patients requiring restorations for root caries. PMID- 1854443 TI - Microleakage of three resin placement techniques. AB - The microleakage associated with three composite resin placement techniques was compared using Class V preparations that extended just beyond the cemento-enamel junction of extracted human molars. The placement techniques were evaluated in conjunction with four adhesive bonding agents. The restored teeth were stored in tap water for 24 hours and then thermally stressed for 100 temperature cycles. Marginal leakage was assessed by measuring the linear penetration of a dye solution. Dye penetration was minimized by using an incremental placement procedure in which the first increment was placed in the coronal portion of the cavity, extended down to the gingivo-axial line angle, and cured. The second increment was used to fill the remainder of the preparation. PMID- 1854444 TI - Marginal ridge strength in Class II tunnel restorations. AB - This in vitro study evaluated the compressive fracture resistance of marginal ridges of teeth with Class II tunnel preparations. Tunnel preparations were completed in extracted human bicuspid and molar teeth (bicuspids, bur size: #2, #4, #6; molars, bur size: #4, #6, #8). Control teeth in both the molar and bicuspid groups remained unprepared. Half the preparations in each group were restored with a glass ionomer cermet. After thermocycling, each marginal ridge was loaded in compression in an Instron Universal testing machine. Fracture values were compared with a two-factor ANOVA. A Dunnet post hoc test was used to compare the strength of each group to its control. Results indicated that up to a certain size, tunnel preparations could be completed without diminishing the strength of the undermined marginal ridges. Placement of a glass-ionomer cermet in the tunnel preparations restored the strength of all but the largest preparations (#6 bur in the bicuspid group) to a level which was not statistically significantly different from the controls. PMID- 1854445 TI - Clinical efficacy of an anticalculus fluoride dentifrice containing triclosan and a copolymer: a 6-month study. AB - A 6-month, double-blind, parallel and unsupervised clinical study was conducted to compare the effects on supragingival calculus formation of a dentifrice containing 0.3% triclosan and 2.0% of a copolymer in a 0.243% sodium fluoride/silica base, as compared to a placebo dentifrice containing 0.243% sodium fluoride in a silica base. Subjects were initially stratified into two balanced groups based on their Volpe-Manhold calculus index scores that were obtained from a 3-month pre-test period using a placebo dentifrice. All subjects received an oral prophylaxis and were assigned to the use of either the fluoride/triclosan/copolymer dentifrice or the placebo dentifrice. Seventy adult male and female subjects completed the entire 6-month study. The results after 3 months' use of their respective dentifrices indicated that the subjects using the fluoride/triclosan/copolymer dentifrice had 26.34% less supragingival calculus formation than the subjects using the placebo dentifrice. This reduction in supragingival calculus was significant at the 99% level of confidence. The results after 6 months indicated that the subjects using the fluoride/triclosan/copolymer dentifrice had 36.27% less supragingival calculus formation than the subjects using the placebo dentifrice. This reduction was significant at the 99% level of confidence. PMID- 1854446 TI - Delayed cementation and bond strength of dual-cure cements. AB - The purpose of this study was to determine whether the shear bond strength to enamel of three dual-cure resin cements is affected by delaying the time between cement mix and application. Etched, silanated Dicor cylinders were bonded to etched enamel with each cement at various time intervals: Immediately after mix, just prior to chemical set and at an intermediate time. Shear bond values were determined using the Instron. No significant differences were found among any of the cements at any of the times. The clinical implication is that as long as these cements remain fluid, there will not be a significant change in the bond strength of Dicor to enamel. PMID- 1854447 TI - Dual-arch and custom tray impression accuracy. AB - This study compared the accuracy in three dimensions of casts made from complete arch custom acrylic resin trays and two types of dual-arch impression trays. Using addition silicone impression material, 30 impressions (10/group) were made of a typodont. Reference marks on the typodont allowed measurements in the mesiodistal, buccolingual and occlusogingival dimensions. Gypsum casts were made and the distances between the reference marks on each cast were determined with a measuring microscope. The measurements from each cast were compared with one another and expressed as a percent deviation from the typodont measurements. Analysis with a two-way ANOVA and a Tukey B post hoc test established that the dual-arch trays were at least as accurate as the custom tray in every dimension measured. PMID- 1854448 TI - Removal of intrinsic enamel stains with vital bleaching and modified microabrasion. AB - This study utilized a vital bleaching agent as well as an enamel microabrasion compound with low hydrochloric acid concentration to remove intrinsic stains on the facial surfaces of anterior teeth. In addition, scanning electron microscopic analyses of enamel from extracted teeth compared the etching pattern of the commercial compound used in this study to 18% hydrochloric acid. Type 1 and Type 2 etch patterns were observed with 18% hydrochloric acid after 5 and 20 seconds, respectively. Milder and more diffuse etch patterns were observed with the enamel microabrasion compound. A conservative form of treatment to remove intrinsic stains would employ the use of a vital bleaching agent, followed by an enamel microabrasion compound. PMID- 1854449 TI - Nonpeptide angiotensin II receptor antagonists. Introduction. PMID- 1854450 TI - Nonpeptide angiotensin II receptor antagonists: a new concept for pharmacologic control of the renin system. A symposium. PMID- 1854451 TI - Renin system blockade as a therapeutic strategy. Past, present, and future. PMID- 1854452 TI - The discovery of a new class of highly specific nonpeptide angiotensin II receptor antagonists. AB - Since angiotensin II (AII) is the effector molecule of the renin angiotensin system, the most direct approach to interfere with this system would be to antagonize AII at the level of its receptor. AII receptor antagonists would represent an ideal species, for regardless of how and where AII is produced, its function could be specifically turned off. However, the AII receptor antagonists currently available have been limited to AII-like peptides and their usefulness as therapeutics and pharmacologic tools has been hampered by their lack of oral bioavailability, metabolic instability, and partial agonistic activity. A detailed pharmacologic characterization of some simple N-benzylimidazoles, originally described by Takeda Chemical Industries (Osaka, Japan), identified this class of compound as very weak but selective AII receptor antagonists with a competitive mode of action. Encouraged by the quality of these lead compounds, we embarked on a synthetic program aimed at designing more potent and orally effective antagonists, while preserving their selectivity for the AII receptor. Our efforts have culminated in the discovery of DuP 753, 2-n-butyl-4-chloro-5 hydroxymethyl-1-[2'-(1H-tetrazol-5-yl)biph eny l-4-yl) methyl]imidazole, potassium salt, a potent, nonpeptide AII receptor antagonist. PMID- 1854453 TI - In vitro pharmacology of DuP 753. AB - DuP 753, 2-n-butyl-4-chloro-5-hydroxymethyl-1-[2'-(1H-tetrazol-5-yl) biphenyl-4 yl)methyl]imidazole, potassium salt, was characterized in vitro with respect to its affinity and specificity for functional antagonism of angiotensin II (AII) receptors. In rat adrenal cortical microsomes and cultured aortic smooth muscle cells DuP 753 inhibited the specific binding of [125I]AII in a concentration dependent manner yielding IC50 values of 1.7 and 2.0 x 10(-8) mol/L, respectively. In contrast, DuP 753 had no appreciable affinity for other receptor systems as well as for Ca2+ channels. Functional antagonism was demonstrated by its blockade of AII-induced 45Ca2+ efflux in rat smooth muscle cells. The AII induced contraction of rabbit aortic strips was competitively antagonized by DuP 753 resulting in a pA2 value of 8.48. Responses induced by other agonists, such as norepinephrine and KCl, were not altered. No partial agonistic effect was noted in any of the in vitro assays. In addition, DuP 753 (10(-5) mol/L) had no effect on rabbit lung converting enzyme or rat/human renin activity. These data demonstrate that DuP 753 is a highly potent and specific AII receptor antagonist. DuP 753 represents a useful experimental tool for dissecting the role of the renin-angiotensin system. PMID- 1854454 TI - In vivo pharmacology of DuP 753. AB - A review of the in vivo pharmacology of DuP 753 (2-n-butyl-4-chloro-5 hydroxymethyl-1-[2'-(1H-tetrazol-5-yl)biphen yl-4- yl)methyl]imidazole, potassium salt) is presented. In the pithed rat, DuP 753 exerted a selective and competitive inhibition of the pressor response to angiotensin II (AII). In conscious normotensive rats, DuP 753 inhibited the AII-induced aldosterone secretion and drinking response. DuP 753 lowered blood pressure in conscious normotensive rats pretreated with furosemide but not in untreated normotensive rats. Unlike saralasin, DuP 753 given intravenously did not cause pressor response. In conscious renal hypertensive rats (RHRs), a high renin model, DuP 753 decreased blood pressure with an intravenous ED30 of 0.78 mg/kg and an oral ED30 of 0.59 mg/kg. The antihypertensive efficacy of DuP 753 in RHRs was similar to that of captopril. In DOCA hypertensive rats, a low renin model, DuP 753 did not lower blood pressure. In conscious 18- to 21-week-old spontaneously hypertensive rats (SHRs), DuP 753 given orally or intravenously reduced blood pressure dose-dependently and did not alter heart rate at these doses. The acute antihypertensive efficacy of DuP 753 was greater than that of captopril in SHRs. In contrast, DuP 753 and captopril given orally at 10 mg/kg/day for 15 days in SHRs caused a similar decrease in blood pressure. Bilateral nephrectomy but not inhibition of prostaglandin synthesis abolished the antihypertensive effect of DuP 753 in SHRs. Our study, therefore, indicates that DuP 753 is an orally active, nonpeptide, selective, and competitive AII receptor antagonist lacking agonism. It appears that there is a relationship between basal renin level and the acute antihypertensive effect of DuP 753 in rats. Further, our results suggest that the renin-angiotensin system plays a significant role in the control of blood pressure in conscious SHRs. PMID- 1854455 TI - Angiotensin II receptor heterogeneity. AB - The possibility of receptor heterogeneity in the angiotensin II (AII) system has been suggested previously, based on differences in Kd values or sensitivity to thiol reagents. One of our earliest indications was the frequent observation of incomplete inhibition of the binding of AII to adrenal cortical membranes. Autoradiographic studies demonstrated that all of the labeling of the rat adrenal was blocked by unlabeled AII or saralasin, but not by DuP 753. The predominant receptor in the rat adrenal cortex (80%) is sensitive to dithiothreitol (DTT) and DuP 753, and is designated AII-1. The residual sites in the adrenal cortex and almost all of the sites in the rat adrenal medulla are insensitive to both DTT and DuP 753, but were blocked by EXP655. These sites have been confirmed by ligand binding studies and are designated AII-2. The rabbit adrenal cortex is unique in yielding a nonuniform distribution of AII-2 sites around the outer layer of glomerulosa cells. In the rabbit kidney, the sites on the glomeruli are AII-1, but the sites on the kidney capsule are AII-2. Angiotensin III appears to have a higher affinity for AII-2 sites since it inhibits the binding to the rabbit kidney capsule but not the glomeruli. Elucidation of the distribution and function of these diverse sites should permit the development of more selective and specific therapeutic strategies. PMID- 1854456 TI - DuP 753 is a potent nonpeptide antagonist of angiotensin II receptors in isolated perfused rat kidney and cultured renal cells. AB - In the present study we investigated the antagonist action of DuP 753 (2-n-butyl 4-chloro-5-hydroxy-methyl-1-[2'-(1H-tetrazol-5-yl)biphe nyl-4-yl) methyl]imidazole, potassium salt) on angiotensin II (AII) binding and vascular effects in the isolated perfused rat kidney. In addition, we determined binding of DuP 753 in cultured glomerular mesangial cells and renomedullary interstitial cells. In the isolated kidney, DuP 753 fully displaced AII from its specific binding sites with high affinity (IC50 = 200 nmol/L) and antagonized the vasoconstrictive effect of AII in a dose-related manner with an ED50 of 170 nmol/L. These effects of DuP 753 were qualitatively similar to those of saralasin and the antagonist effect of DuP 753 on AII-induced renal vasoconstriction was fully overcome by excess AII. DuP 753 had no effect on its own on renal vascular resistance. In cultured glomerular mesangial cells and renomedullary interstitial cells, DuP 753 fully inhibited the specific binding of [125I]-Sar-AII at 1 mumol/L with IC50s of 6.7 and 11 nmol/L for glomerular mesangial cells and renomedullary interstitial cells, respectively. The present results demonstrate that a novel imidazole derivative, DuP 753, is a powerful non-peptide antagonist of angiotensin II receptors in isolated perfused rat kidney and in cultured glomerular mesangial and renomedullary interstitial cells. PMID- 1854457 TI - Characterization of the renal microvascular effects of angiotensin II antagonist, DuP 753: studies in isolated perfused hydronephrotic kidneys. AB - The renal microvascular effects of DuP 753, an orally active imidazole angiotensin II (ANG II) receptor antagonist were assessed directly in isolated perfused hydronephrotic rat kidneys. Unilateral hydronephrosis was induced to facilitate direct visualization of renal microvessels. Hydronephrotic kidneys were perfused in vitro and microvessel diameters were measured by automated computer-assisted image processing. The administration of 0.3 nmol/L ANG II decreased afferent arteriolar (AA) and efferent arteriolar (EA) diameters by 34 +/- 3% (from 17.9 +/- 0.6 to 11.9 +/- 0.6 microns, P less than .001, n = 11) and 28 +/- 3% (from 17.1 +/- 1.3 to 12.3 +/- 1.3 microns, P less than .001, n = 11), respectively. The subsequent administration of 0.1, 1.0, and 10 mumols/L DuP 753 reversed ANG II-induced vasoconstriction of the AA by 39 +/- 10%, 81 +/- 8%, and 103 +/- 9%, and of the EA by 22 +/- 7%, 51 +/- 6%, and 87 +/- 13%, respectively. These observations indicate that DuP 753 completely blocks both the renal afferent and efferent arteriolar actions of ANG II. In light of the pathogenetic role of ANG II in mediating the deranged renal hemodynamics associated with hypertension, congestive heart failure, and some forms of renal insufficiency, our findings provide a theoretical framework for future studies assessing the potential therapeutic applicability of DuP 753 in reversing ANG II-mediated renal vasoconstriction. PMID- 1854458 TI - Effects of DuP 753 on proximal nephron and renal transport. AB - We used the nonpeptide angiotensin II receptor antagonist DuP 753, which lacks the agonist and kinin/prostaglandin-inducing properties of saralasin and captopril, respectively, to examine the role of endogenous angiotensin II in regulating transport in the proximal convoluted tubule (PCT) and whole kidney. During in vivo microperfusion in the Munich-Wistar rat, a maximally effective dose of DuP 753 (10 mg/kg, intravenously) powerfully inhibited absorption of bicarbonate (370 +/- 3 to 200 +/- 9 pEq/mm.min, P less than .001), chloride (214 +/- 3 to 105 +/- 9 pEq/mm.min, P less than .001), and water 5.2 +/- 0.1 to 2.8 +/ 0.2 nL/mm.min, P less than .001) in the S1 subsegment of the PCT. DuP 753 was significantly more effective than captopril (3 mg/kg, intravenously) in inhibiting sodium chloride transport and is the most potent diuretic ever described in this segment. Consistent with the axial decline of angiotensin II receptor density in the PCT, DuP 753 was a less effective transport inhibitor in the S2 subsegment of the PCT, similar to captopril. Using free-flow micropuncture and clearance techniques, though inhibition in the earliest segment of the nephron is partially compensated by downstream reabsorption, DuP 753 induces a substantial diuresis, natriuresis, and chloruresis. In conclusion, DuP 753 markedly decreases S1 PCT fluid and electrolyte absorption, indicating that endogenous angiotensin II exerts significant tonic support of proximal transport in vivo. PMID- 1854459 TI - Effects of DuP 753 on renal function of normotensive and spontaneously hypertensive rats. AB - This study examined the effects of a new, orally-active, nonpeptide angiotensin II (AII) receptor antagonist, 2-n-butyl-4-chloro-5-hydroxymethyl-1-[2'-(1H tetrazol-5-yl)biph eny l-4- yl)methyl] imidazole, DuP 753, on renal function of anesthetized, volume-expanded Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR), and in a group of euvolemic Munich-Wistar (MW) rats. Plasma renin activities were similar and averaged 4.4 +/- 0.7 and 4.3 +/- 1.4 ng AI/mL.h, respectively, in the SHR and WKY rats. In WKY rats (n = 15), DuP 753 (2 or 10 mg/kg, intravenously) had no effect on urine flow, sodium excretion, renal blood flow (RBF), or glomerular filtration rate (GFR). Fractional excretion of lithium (FELi) rose from 32 +/- 5 to 40 +/- 4% of the filtered load and arterial pressure decreased slightly from 129 +/- 2 to 122 +/- 2 mm Hg. In SHR (n = 9), urine flow fell 24%, and FELi and RBF increased by 27% and 30%, respectively, after 2 mg/kg DuP 753, but sodium excretion, GFR, and arterial pressure were not significantly altered. A higher dose of DuP 753 (10 mg/kg; n = 8) reduced arterial pressure, urine flow, and sodium excretion in the SHR. RBF increased 34%, while GFR and FELi were not significantly altered. Similar effects were seen in SHR (n = 11), given an equivalent antihypertensive dose of captopril (20 mg/kg). In euvolemic MW rats in which plasma renin activity was elevated to 18.8 +/- 3.3 ng AI/mL.h, DuP 753 (2 mg/kg, n = 7) increased RBF, urine flow, and sodium excretion, while mean arterial pressure and GFR were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854460 TI - Effects of the nonpeptide angiotensin II receptor antagonist DuP 753 on blood pressure and renal functions in spontaneously hypertensive PH dogs. AB - A colony of genetic hypertensive dogs with systolic blood pressure of 140 to 220 mm Hg and diastolic blood pressure greater than 100 mm Hg in the trained state was used. The objective of this study was to investigate the hemodynamic and renal effects of the novel angiotensin II receptor antagonist DuP 753 given intravenously to these dogs. Renal functions and blood pressure were measured 45 to 75 min after the intravenous administration of DuP 753 at 1, 3, 10, and 30 mg/kg and were compared to control (placebo) treatment. Arterial pressure was slightly but significantly and dose-dependently reduced by DuP 753. Glomerular filtration rate increased significantly in a dose-dependent manner. Similarly, effective renal plasma flow was dose-dependently increased. Filtration fraction was unchanged. Renal vascular resistance was significantly reduced in a dose dependent manner at 3, 10, and 30 mg/kg of DuP 753. DuP 753 increased fractional sodium excretion at all doses and increased fractional potassium excretion only at the highest doses. The vasopressor effects of angiotensin I and II were dose dependently inhibited by DuP 753. These data show that DuP 753 has beneficial renal hemodynamic effects and lowers arterial pressure in this canine model of essential hypertension. PMID- 1854461 TI - Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in rat model of heart failure. AB - The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with captopril to direct blockade of angiotensin II (AII) with DuP 753 in the rat model of heart failure. Rats with chronic heart failure postinfarction were treated for 2 weeks with either captopril (2 g/L, N = 9) in their drinking water or with DuP 753 (40 mg/kg/day for two weeks by gastric gavage, N = 10), or placebo (N = 9). At this dose, DuP 753 shifted the log dose pressor response curve to AII parallel to the right by two orders of magnitude in both chronically treated normal and heart failure rats. In rats with heart failure, DuP 753 and captopril reduced left ventricular end-diastolic pressure from 26.7 +/- 1.5 to 14.2 +/- 3.0 (P less than .01) and 15.8 +/- 2.2 mm Hg (P less than .05), respectively, left ventricular end-diastolic volume index from 2.71 +/- 0.10 to 2.03 +/- 0.17 (P less than .05) and 2.18 +/- 0.15 (P less than .05), respectively; venous compliance increased from 2.27 +/- 0.06 to 2.80 +/- 0.18 (P less than .05) and 3.02 +/- 0.21 mL/mm Hg/kg (P less than .01), respectively. There were no significant changes in left ventricular weight/body weight ratio, mean aortic pressure, heart rate, or right atrial pressure. There was a trend, but not significant, for a reduction in total blood volume from 65.8 +/- 1.1 to 59.4 +/- 3.0 and 64.9 +/- 3.9 mL/kg, respectively. Thus, direct blockade of AII with DuP 753 or with converting enzyme inhibition with captopril produces similar hemodynamic changes in rats with heart failure after myocardial infarction. PMID- 1854462 TI - DuP 753 increases survival in spontaneously hypertensive stroke-prone rats fed a high sodium diet. AB - We studied the effects of the nonpeptide angiotensin II receptor antagonist, DuP 753, on blood pressure, body weight, plasma renin activity, sodium excretion, and mortality in male stroke-prone spontaneously hypertensive rats (SHRsp) fed a 4% NaCl diet for 12 weeks. The rise in blood pressure, due to high sodium intake, was blunted in the first 8 weeks of the study in the DuP 753-treated group; however, it started slowly to rise in the following weeks. In the untreated group, blood pressure rose steadily and it was significantly higher than that of the treated group during the whole experimental period. DuP 753-treated rats gained weight continuously during the study in contrast to the untreated group, where weight gain was arrested after 4 weeks. Plasma renin activity rose significantly after 4 weeks of treatment with DuP 753; by week 6 its values returned to baseline values and remained at these lower values until week 12. In the untreated group, plasma renin activity was not suppressed by high sodium intake after 4 weeks; it continued to rise and it was significantly elevated by 8 and 12 weeks. Survival at 12 weeks was 84% in DuP 753-treated group and 26% in the untreated group. The data demonstrate that DuP 753 decreased mortality and dramatically blunted the blood pressure rise in SHRsp fed a high sodium diet. PMID- 1854463 TI - Angiotensin II receptor antagonist markedly reduces mortality in salt-loaded Dahl S rats. AB - We investigated the effect of blockade of the renin-angiotensin system (RAS) on morbidity and hypertension in salt-loaded Dahl salt-sensitive (Dahl S) rats. Six week-old male Dahl S rats (n = 198) were fed a high sodium diet (8% NaCl) for 10 weeks. One group of rats (n = 91) was treated with 30 mg/kg/day of the nonpeptide angiotensin II receptor antagonist, DuP 753, whereas the control group (n = 107) was left untreated. Blood pressure rose steeply in both groups, reaching levels above 200 mm Hg by week 6. DuP 753-treated animals were less hypertensive than controls between weeks 3 and 5 of the study, but had similar blood pressure before and after that time. Although the angiotensin II antagonist had only a transient effect on blood pressure it markedly prolonged survival. After 10 weeks, 68.3% of rats receiving DuP 753, but only 30.1% of controls, were still alive (P less than .0001). Higher morbidity in controls than in DuP 753-treated rats was also suggested by body weights. Following 6 weeks of high salt diet, untreated rats progressively lost weight while DuP 753-treated animals maintained a steady body weight. These results show that the angiotensin II receptor antagonist DuP 753 greatly enhanced survival in salt-loaded Dahl S rats although it reduced blood pressure only transiently. Our data are consistent with a contribution of the RAS to morbidity in this model of hypertension. PMID- 1854464 TI - Dose-response relationships following oral administration of DuP 753 to normal humans. AB - We assessed the inhibitory effect of DuP 753, an orally active angiotensin II receptor antagonist, on the pressor action of exogenous angiotensin I and II in healthy volunteers. In a single dose study, doses of 2.5, 5, 10, 20, and 40 mg of DuP 753 or placebo were tested serially at one week intervals. In the multiple dose study, the administration of placebo or DuP 735 (5, 10, 20, or 40 mg, per os once daily) for eight consecutive days was evaluated. The blood pressure response to angiotensin I and II was inhibited in a dose-dependent fashion with a blocking effect still present 24 h post drug. DuP 753 also induced a dose-dependent compensatory rise in plasma renin. This new compound was well tolerated by these normal volunteers. Thus, DuP 753 appears to be a well tolerated, orally active, potent and long-lasting antagonist of angiotensin II in humans. PMID- 1854465 TI - Consistency of hand preference: predictions to intelligence and school achievement. AB - Gottfried and Bathurst (1983) reported that hand preference consistency measured over time during infancy and early childhood predicts intellectual precocity for females, but not for males. In the present study longitudinal assessments of children previously classified by Gottfried and Bathurst as consistent or nonconsistent in cross-time hand preference were conducted during middle childhood (ages 5 to 9). Findings show that (a) early measurement of hand preference consistency for females predicts school-age intellectual precocity, (b) the locus of the difference between consistent vs. nonconsistent females is in verbal intelligence, and (c) the precocity of the consistent females was also revealed on tests of school achievement, particularly tests of reading and mathematics. PMID- 1854466 TI - The occurrence of different intrusive errors in patients with Alzheimer's disease, multiple cerebral infarctions, and major depression. AB - Recent evidence suggests that specific types of intrusive errors may occur more often in the protocols of Alzheimer's disease (AD) patients than in those of patients diagnosed with other types of dementia. Using the FULD Object Memory Evaluation, we documented the occurrence of five qualitatively different types of intrusive errors for mildly and moderately impaired patients with AD and multiple cerebral infarctions (MCI). Depressed and normal elderly controls were also studied. Despite an equivalent degree of impairment on a broad array of neuropsychological measures, mildly impaired AD patients evidenced greater deficits on a measure tapping retrieval from semantic memory and demonstrated a higher occurrence of specific types of intrusive errors relative to their mildly impaired MCI counterparts. Further, both of these measures were highly correlated, suggesting that these indices may be particularly sensitive to semantic dysfunction associated with early AD. PMID- 1854467 TI - Visual neglect and left-sided context effects. AB - Patients with visual neglect generally fail to respond to an item placed on the left of a target location, even when both stimuli are situated in the right visual field. Little is known, however, about the level of processing for the unattended items. Two patients with left visual neglect served as subjects in several experiments measuring passive contextual effects of a left-sided item on responses to a focal target. The results reveal that a neglected item may influence the speed of responding. The findings are interpreted relative to the loci of context effects in normal subjects. PMID- 1854468 TI - Denial of visual perception. AB - An adult with the diagnosis of cortical blindness, complaining of a complete visual loss of 2 years in duration, was found to have a small preserved visual field and remarkably preserved visual abilities. Although denying visual perception, he correctly named objects, colors, and famous faces, recognized facial emotions, and read various types of single words with greater than 50% accuracy when presented in the upper right visual field. Upon confrontation regarding his apparent visual abilities, the patient continued to deny visual perceptual awareness, typically stating "I feel it." CT indicated bioccipital lesions sparing the left inferior occipital area but involving the left parietal lobe. The denial of visual perception evidenced by this patient may be explained by a disconnection of parietal lobe attentional systems from visual perception. The clinical presentation is described as representing "inverse Anton's syndrome." PMID- 1854469 TI - Effects of handedness and sex on the morphology of the corpus callosum: a study with brain magnetic resonance imaging. AB - In view of conflicting data in the existing literature, we examined 53 normal subjects using a handedness questionnaire and callosal area measurements obtained from midsagittal MRI images. The callosum was found to be significantly larger in nonconsistent right-handers (NCRH), especially in its anterior half and especially for males. A significant hand x sex interaction, favoring consistent right-handed (CRH) females, was also found for the posterior midbody, a region known to house interhemispheric fibers connecting the right and left posterior association cortices. These results (1) confirm Witelson's (1985) first findings on postmortem specimens; (2) validate a dichotomy between CRH and NCRH rather than simply considering the writing hand, as was the case in most other similar studies; and (3) suggest that at least two different sex-related--probably hormonal--factors may be acting during the callosal development, one explaining the larger anterior half in NCRH males and the other the larger posterior midbody in CRH females. PMID- 1854470 TI - Hemispheric asymmetry in the processing of absolute versus relative spatial frequency. AB - Observers indicated whether a stimulus presented to one visual field or the other consisted of two sine-wave gratings (the baseline stimulus) or those same two gratings with the addition of a 2 cycle per degree (cpd) component. When the absolute spatial frequencies of the baseline stimulus were low (0.5 and 1.0 cpd), there was a left visual field-right hemisphere (LVF-RH) advantage in reaction time (RT) to respond to the baseline stimulus which disappeared when the 2 cpd component was added (i.e., the stimulus consisted of 0.5, 1.0, and 2.0 cpd components). When the absolute spatial frequencies of the baseline stimulus were moderate to high (4.0 and 8.0 cpd), a right visual field-left hemisphere advantage in RT to respond to the baseline stimulus approached significance and shifted to a significant LVF-RH advantage when the 2 cpd component was added (i.e., the stimulus consisted of 2.0, 4.0, and 8.0 cpd components. That is, adding the same 2 cpd component caused opposite shifts in visual laterality depending on whether 2 cpd was a relatively high or relatively low frequency compared to the baseline. PMID- 1854471 TI - Sensory and motor aspects of pseudoneglect, hemifield, and hemispace in the tactile modality. AB - Two experiments were conducted with right-handed adult subjects to investigate motor and sensory components of a tactual line bisection task performed under three conditions: at midline, in the left, and in the right hemispaces. In the sensory experiment we found a left-hand rather than a right-hand superiority under the midline condition and, in the motor experiment, a right-hand rather than a left-hand superiority. The results were discussed with respect to hemispheric specialization and hemispace theories. Furthermore, we found a pseudoneglect (subjects bisected to the left of the midpoint) in the sensory experiment and a surprising reversed pseudoneglect (subjects bisected to the right of the midpoint) in the motor experiment. PMID- 1854472 TI - Perceptual asymmetries for free viewing of several types of chimeric stimuli. AB - We examined perceptual biases of right-handers on six free-vision chimeric tasks; two involving a judgement of happiness of a facial expression in photographic and cartoon chimeras, two involving a judgement of femininity in male/female photographic and cartoon chimeras, and two involving a spatial judgement of nonface chimeric stimuli. All four of the face tasks and one of the nonface tasks elicited left spatial field biases of varying magnitudes, and perceptual asymmetries on all tasks were positively correlated. However, multiple correlational analyses revealed that these tests shared differing proportions of variance with each other. Results indicate that, in addition to a common factor or set of factors contributing to lateral biases that is independent of both the nature of the stimulus and whether the stimulus engages lateralized mechanisms, there are distinct lateralized mechanisms which yield different patterns of perceptual asymmetries for different stimuli. PMID- 1854473 TI - Assembly of cytoplasmic and smooth muscle myosins. AB - Filaments formed from a variety of smooth and non-muscle myosins are dynamic polymers whose phosphorylation-dependent assembly and disassembly can be coupled to changes in enzymatic activity. Phosphorylation-insensitive assembly, which allows independent control of activity and polymerization, is an alternative mechanism used by Acanthamoeba myosin. Domains of the tail responsible for assembly and regulation have now been identified for a number of myosins. PMID- 1854474 TI - Elastic filaments and giant proteins in muscle. AB - Striated muscle is now known to contain a third major class of filaments, additional to the thick and thin filaments. The presence of such extra filaments has seemed likely for many years, but details of their location, structure, and composition are only now becoming clear. They are composed of massively large proteins and, in contrast to thick and thin filaments, they are elastic. PMID- 1854475 TI - Nucleotide hydrolysis in cytoskeletal assembly. AB - Two major polymers of the cytoskeleton, actin filaments and microtubules, are assembled with expenditure of energy: the ATP/GTP tightly bound to actin/tubulin is irreversibly hydrolyzed to ADP/GTP during the assembly process, and liberation of Pi in the medium occurs subsequent to the incorporation of subunits in the polymer. Pi release acts as a switch, causing the destabilization of protein protein interactions in the polymer, therefore regulating the dynamics of these fibres. An understanding of this regulation in vivo requires that progress be made in four areas: the chemistry of the NTPase reaction; the structure of the intermediates in nucleotide hydrolysis and the nature of the conformational switch; the regulation of parameters involved in dynamic instability of microtubules; and the possible involvement of nucleotide hydrolysis in the macroscopic organization of these polymers in highly concentrated solutions, compared with the simple case of a equilibrium polymers. Progress made along these lines will define trends for future investigation. PMID- 1854476 TI - Molecular links between the cytoskeleton and membranes. AB - This review covers recent advances in non-erythroid spectrin re-distributions during development, structural motifs recently discovered in ankyrin, band 4.2, band 4.1, ezrin, talin, and myosin I, and our present understanding of actin membrane interactions at focal adhesions and in liver, platelet, and Dictyostelium discoideum plasma membranes. PMID- 1854477 TI - Intermediate filament-plasma membrane interactions. AB - In this review we will discuss the molecules involved in intermediate filament desmosome and intermediate filament-hemidesmosome interactions, and the means by which certain of these molecules may bind to intermediate filaments. The possibility that intermediate filaments interact directly with peripheral membrane proteins and membrane lipids will also be addressed. PMID- 1854478 TI - Cytoplasm and cell motility. PMID- 1854479 TI - Phenotypes of cells with cytoskeletal mutations. AB - Analysis of the cytoskeleton has relied heavily on the identification of phenotypic alterations associated with mutations in cytoskeletal components. This approach has led to important findings for specific proteins. The last year has also strengthened the view that certain functions of the cytoskeleton are safeguarded by the presence of multiple protein forms. PMID- 1854480 TI - Dynamics of the cytoskeleton in live cells. AB - Actin filaments, microtubules, and intermediate filaments, have all been found to be dynamic structures in living cells. Recent studies have shed important light on the assembly, disassembly, and mobility of these structures. In addition, a growing emphasis has been placed on the regulation of cytoskeletal activities by various signal transduction pathways. PMID- 1854481 TI - The plant cytoskeleton. AB - Significant progress has been made in four areas: in appreciating the speed with which cortical microtubules reorient in response to environmental signals; in a consolidated understanding of the cytoskeletal nature of the phragmosome--the device that predicts and structures the division plane in vacuolated cells; in the description of new cytoskeletal proteins; and in reports that herald an attack on the cell cycle control of cytoskeletal organization. PMID- 1854482 TI - Mechanical properties of cytoskeletal polymers. AB - The mechanical properties of cytoplasm are dominated by microfilaments, microtubules, and intermediate filaments, collectively termed the cytoskeleton. This review discusses how the physical properties of these biopolymer systems are related to their molecular structures and interactions, and how remodelling of these biopolymers in vivo affects cell shape and motility. PMID- 1854483 TI - Functions of tubulin isoforms. AB - The biological significance of tubulin isotypes lies in their ability to function in different chemical and physical environments. Recent papers document the origin and distribution of several new tubulin isotypes and suggest new ways for studying their assembly and function in specialized cells. PMID- 1854484 TI - Non-motor microtubule-associated proteins. AB - Cloning of primary sequences has generated information on the structures of the non-motor microtubule-associated proteins and their relationship to one another. Questions about how classes of microtubule-associated proteins interact are starting to be addressed in vitro and, in vivo, tests of function are being pursued using a variety of cellular and molecular biological strategies. PMID- 1854485 TI - Mitosis: towards a molecular understanding of chromosome behavior. AB - The past year has seen important contributions made to resolving how chromosomes attach to and move on the mitotic spindle of animal cells. These include the findings that: kinetochore microtubules are derived from the asters (i.e. centrosomes); poleward chromosome motion need not be coupled to kinetochore microtubules disassembly; the motor for poleward chromosome motion is associated with the kinetochore; and immunological evidence that this motor is cytoplasmic dynein. PMID- 1854486 TI - Regulation of intermediate filament gene expression. AB - Members of the intermediate filament protein family exhibit complex patterns of development-specific and tissue-specific expression. Studies exploring the mechanisms of gene regulation are underway and key regulatory factors are currently being described and isolated for certain genes encoding intermediate filament proteins. Selected systems from this diverse group of about 50 genes will be discussed. PMID- 1854487 TI - Intermediate filament-associated proteins. AB - The term intermediate filament-associated proteins refers to a growing number of proteins whose ability to interact with intermediate filaments has been either directly demonstrated or inferred from indirect evidence. Here we discuss recently published data on the identification and characterization of such proteins, with emphasis on their tissue/cell type-specific expression, subcellular distribution and possible function(s). PMID- 1854488 TI - Nuclear lamin proteins: domains required for nuclear targeting, assembly, and cell-cycle-regulated dynamics. AB - The nuclear lamin proteins assemble at the nuclear membrane into a highly dynamic network whose integrity is exquisitely controlled by the major cell cycle regulators. Although the actual cellular functions of the lamins remain elusive, the processes of targeted lamin assembly and phosphorylation-induced disassembly have come to light recently. These processes require functionally interacting lamin domains to execute targeting to the nucleus and the nuclear membranes, lamina assembly, and the disassembly response to cell-cycle-dependent phosphorylation. PMID- 1854489 TI - Actin-binding proteins. AB - Much new information on the sequence, structure, and function of filament crosslinking, capping, and severing proteins is now known. Other significant findings include identification of a new abundant monomer-sequestering protein in platelets, and evidence that many actin-binding proteins interact with phosphoinositides and that this interaction may have metabolic consequences. PMID- 1854490 TI - Regulation of cytoplasmic and smooth muscle myosin. PMID- 1854491 TI - Echocardiography in serial evaluation of left ventricular systolic and diastolic function: importance of image acquisition, quantitation, and physiologic variability in clinical and investigational applications. AB - Quantitative echocardiography is frequently used for serial evaluation of left ventricular performance. This prospective study was designed to determine the extent to which the acts of image acquisition and quantitation, and the subjects themselves, affect total variability in two-dimensional and Doppler echocardiographic indexes of left ventricular morphology and performance. Therefore, two technicians and two readers acquired and analyzed 60 echocardiograms from 15 normal subjects, each of whom was studied four times (twice on each of two visits). Analysis of variance based on generalizability theory was used to estimate the magnitude of these variability sources by calculating standard deviations (SD) and used to estimate their contribution to total variability. Of the two-dimensional echocardiographic indexes tested, ejection fraction varied least (SD, 6.6%) and left ventricular mass varied most (SD, 35.3 gm). Of the Doppler indexes, normalized early diastolic filling velocity integral varied least (SD, 8.4%) and deceleration time varied most (SD, 48.6 msec). Technical (image acquisition and quantitation) variability contributed most (and subject variability least) to total variability of stroke volume (68%) and deceleration time (67%). Technical variability contributed least (and subject variability most) to variability of ejection fraction (43%) and diastolic filling time (25%). The acts of image acquisition and quantitation varied more between than within technicians and readers. Peak atrial filling velocity and the ratio of peak early to atrial filling velocity significantly differed between technicians. Left ventricular ejection fraction, left ventricular mass, peak atrial filling velocity, early filling integral, and deceleration of early filling differed significantly between readers. Therefore the acts of image acquisition and quantitation, and subject variability itself, all contribute to total variability in echocardiographic indexes. Changes seen on clinical studies should be interpreted as abnormal only when exceeding the total variability originating from these sources. Generalizability theory allows one to tailor strategies to reduce variability. These strategies include increasing the number of observations, readers, and technicians for any given "baseline" study and using the same readers and technicians for sequential follow-up studies. PMID- 1854492 TI - Predicting left heart failure after a myocardial infarction: a preliminary study of the value of echocardiographic measures of left ventricular filling and wall motion. AB - Heart failure occurs from both systolic and diastolic dysfunction. To determine whether simple Doppler echocardiographic measures of left ventricular filling could improve upon the ability of systolic function to predict heart failure after infarction, patients with acute myocardial infarction were studied within the first 36 hours by Doppler and two-dimensional echocardiography. Forty-eight patients who did not have heart failure before the Doppler echocardiographic study and who did not have myocardial revascularization, moderate or severe mitral regurgitation, or other complications during recovery were monitored for 6 months or to the onset of heart failure (n = 10). The univariate predictors of heart failure were age (p less than 0.05), anterior infarction (p less than 0.05), early diastolic peak filling velocity (p = 0.05), filling velocity with atrial systole (p less than 0.05), the ratio of these velocities (p less than 0.001), the percentage of filling with atrial systole (p less than 0.001), and the wall motion score index (p less than 0.001). However, the only independent predictors of heart failure by use of multivariant stepwise logistic regression analysis were the wall motion score index (p less than 0.05) and either the ratio of early and late peak filling velocities (p less than 0.001) or the percentage of filling with atrial systole (p less than 0.001). The combined use of a measure of systolic function and measures of the relative contribution of atrial systole to ventricular filling were useful predictors in identifying patients likely to develop subsequent heart failure after myocardial infarction. PMID- 1854493 TI - Reference systems in echocardiographic quantitative wall motion analysis with registration of respiration. AB - Registration of respiration allows analysis at the end-expiratory phase and may thus favor the use of the fixed-reference system versus the floating-reference system in echocardiographic quantitative wall motion analysis. Analysis is performed on two-dimensional echocardiograms of 44 normal subjects, 38 patients with anterior myocardial infarction, and 17 patients with posterior myocardial infarction. Two different models for wall motion analysis are applied, each using the fixed-reference system and the floating-reference system, respectively. In patients with anterior myocardial infarction, the fixed-reference system indicates severe wall motion abnormalities at the anterior, septal, and apical walls, whereas the floating-reference system indicates less severe wall motion abnormalities almost equally at every wall. In patients with posterior myocardial infarction, the fixed-reference system indicates severe wall motion abnormalities at the posterior wall, whereas the floating-reference system indicates less severe wall motion abnormalities almost equally at every wall. These findings indicate that the fixed-reference system is superior to the floating-reference system in quantification of wall motion of end-expiratory two-dimensional echocardiograms. PMID- 1854494 TI - A method for evaluation of enhancement operations in two-dimensional echocardiographic images. AB - A means of estimating the degree of enhancement of structure and suppression of background noise in filtered two-dimensional echocardiographic images is described. The method is termed the peak-to-background ratio. To test the method, two-dimensional short-axis echocardiographic images were enhanced with Laplacian operations of increasing mask size. There was excellent correlation between the calculated peak-to-background ratio and the subjective opinion of trained echocardiographers. Furthermore, radial length measurements made from images that were thought to be optimally enhanced by the peak-to-background ratio calculation showed the lowest interobserver mean differences. We conclude that the peak-to background ratio does reflect improvement in characteristics of the image that favor more precise measurement (amplification of peaks and suppression of background) and can be used to help guide a dynamic approach to image processing. PMID- 1854495 TI - Intraventricular blood flow during isovolumetric relaxation and diastole in hypertrophic cardiomyopathy. AB - Forty patients with hypertrophic cardiomyopathy were investigated by Doppler echocardiography for intraventricular blood flow abnormalities. None had a bundle branch block. The patients were recruited on the basis of the presence of at least one of four different types of abnormal left ventricular blood flow movements during systole, isovolumetric relaxation, and diastole (time after mitral valve opening). The abnormal blood flow patterns were composed of the following: (1) systolic left ventricular outflow and midventricular obstruction in 20 of 40 and in 6 of 40 patients, respectively; (2) retrograde isovolumetric relaxation flow (IVRFretro; mean velocity, 0.7 +/- 0.3 m/sec), that is, flow toward the apex of the left ventricle, in 28 of 40 patients; (3) antegrade isovolumetric relaxation flow (IVRFante; mean velocity, 1.6 +/- 1.0 m/sec), that is, flow toward the left ventricular outflow tract, in 3 of 40 patients; and (4) diastolic antegrade flow (DFante; mean velocity, 0.9 +/- 0.3 m/sec), that is, flow opposite to mitral inflow, in 10 of 40 patients. There were significantly fewer patients with asymmetric septal hypertrophy (group 1) than with apical hypertrophic cardiomyopathy (group 2) showing DFante (1/29 versus 9/11, p less than 0.01). IVRFretro and DFante revealed higher velocities in patients with marked left ventricular asymmetric hypertrophy than in those with mild hypertrophy. Thus, in hypertrophic cardiomyopathy and especially in patients with marked asymmetric hypertrophy, there are different types of abnormal intraventricular blood flow movements during isovolumetric relaxation and disatole. This phenomenon is probably caused by asynchronous relaxation of the asymmetrically distributed, hypertrophied myocardium. DFante is more often observed in the apical cardiomyopathy than other forms of hypertrophic cardiomyopathy probably attributable to apically localized left ventricular cavity obliteration. PMID- 1854496 TI - Respective timing of maximal color Doppler jet areas and of peak velocity of jets in left-sided valvular lesions: clinical implications. AB - Time intervals between the R wave of the electrocardiogram and maximal dimension of jet areas of color Doppler and the R wave of the electrocardiogram and peak velocity of valvular jets of continuous-wave Doppler were compared by use of paired and correlative studies for a group of 55 patients with a total of 71 left sided lesions. Mean values of both time intervals, mean difference, and its standard error were equal to zero for stenoses. Time intervals of 71% for mitral stenosis and 52% for aortic stenosis did not differ by more than 0.01 second; correlation coefficients were 0.96 for mitral stenosis and 0.85 for aortic stenosis. For regurgitations, differences in mean values and a mean difference with a standard error were found but remained unsignificant. However, the percentage of differences in time intervals below or equal to 0.01 second decreased to 35 for aortic regurgitation and 13 for mitral regurgitation, which showed the widest 95% range of differences. Correlation coefficients were 0.84 for the aortic regurgitation and 0.33 for mitral regurgitation. Thus the close relationship of time intervals suggests that standardized timing of area measurements at peak velocity is feasible for stenoses and remains under consideration for aortic regurgitation. Timing of measurements should remain empiric for mitral regurgitation. PMID- 1854497 TI - Anomalous papillary muscle producing dynamic left ventricular outflow tract obstruction. AB - A patient with a dynamic left ventricular outflow murmur was shown to have an anomalous anterolateral papillary muscle by transthoracic and transesophageal two dimensional Doppler echocardiography. High late systolic outflow velocity and systolic anterior motion were demonstrated in the lateral outflow tract near the anomalous muscle, suggesting a role for the Venturi effect. This is the first confirmation by Doppler echocardiography of an anomalous papillary muscle contributing to abnormal left ventricular hemodynamics. PMID- 1854498 TI - An acquired interatrial fistula secondary to para-aortic abscess documented by transesophageal echocardiography. AB - Para-aortic ring abscess and resulting fistulous communication between adjacent structures frequently occur in prosthetic aortic valve endocarditis but are rarely diagnosed preoperatively. We report a patient who had an abscess involving the aortic-mitral intervalvular fibrosa that eroded into the interatrial septum, causing an interatrial communication with a left-to-right shunt. The abscess was detected by transthoracic echocardiography, but the fistula was only seen by the subsequent transesophageal echocardiogram. To our knowledge, this is the first report of an interatrial fistula secondary to a para-aortic valve abscess and its diagnosis preoperatively. Transesophageal echocardiography should be performed in any patient suspected to have complicated aortic endocarditis. PMID- 1854499 TI - The neuroendocrine system of the gut--an update. AB - During the last few years the endocrine stomach has come into focus much due to the side-effects produced by powerful acid blockers. A sustained and marked inhibition of acid secretion in the rat results in hypergastrinemia, with gastrin cell hyperplasia, and a consequent hyperplasia of the ECL cells. This response of the ECL cells was predictable in view of previous observations that sustained hypergastrinemia causes ECL cell hyperplasia. While the gastrin cell hyperplasia levels off at about twice the normal cell density a few weeks after start of treatment, the ECL cells continue to proliferate for months to reach a five-fold higher density than normally. Evidence is accumulating that ECL cells proliferate through self replication. After life-long inhibition of acid production (high doses of ranitidine or omeprazole) or after extirpation of 75% of the acid producing part of the stomach, ECL cell carcinoids develop. Endocrine cells in the gut often contain more than one putative messenger. Thus, gastrin cells in many species store GABA and peptide YY; in e.g. cat and man they store in addition a xenopsin-like peptide. Neuromedin U and pituitary adenylate cyclase activating peptide (PACAP) have recently been demonstrated in gut nerves. Their role in gut physiology remains to be identified. PMID- 1854501 TI - Pancreastatin--a novel regulatory peptide? AB - Pancreastatin is a 49 amino acid peptide originally isolated from porcine pancreas on the basis of its C-terminal glycinamide as isolation criterion. It is derived by proteolytic processing from chromogranin A, an acidic protein component of secretory granules in endocrine and neuronal cells. The primary structures of human, porcine, bovine and rat pancreastatin have been determined on the protein or cDNA level and show 70% sequence homology. By immunocytochemistry, pancreastatin has been detected in the pituitary, adrenal gland, pancreas, CNS and throughout the gastrointestinal tract. In pancreatic islets, pancreastatin is co-localized with insulin, glucagon and somatostatin. The principle biological activities of this peptide are: inhibition of insulin release and of exocrine pancreatic secretion. These effects which can be assigned to the amidated C-terminal part of the molecule have been demonstrated in several species. Whether or not pancreastatin can be classified as a novel peptide hormone that under physiological conditions plays a role in the regulation of the endocrine and exocrine pancreas, is still a matter of controversy. PMID- 1854500 TI - The expression of peptide hormones in normal cells and tumour cells. AB - Insight in the mechanisms of peptide hormone expression has grown explosively by elucidation of gene, mRNA and preprohormone structures for most hormone systems during the 1980s. In addition, information about the structure and substrate specificity of many prohormone processing enzymes is rapidly accumulating in these years. The preprohormones vary considerably in size and organization from poly- to monoprotein structures. According to the structural organization and sequence homology the hormones are grouped in families. The prohormones are processed to bioactive peptides by multiple enzymatic modifications during the intracellular transport from the rough endoplasmatic reticulum to the mature secretory granules. The modifications comprise different proteolytic cleavages and amino acid derivatizations. The same prohormone may be expressed in several different cell types that process the precursor in entirely different ways. Awareness of such cell-specific processing patterns is important for the understanding of ectopic synthesis in neuroendocrine tumours. PMID- 1854502 TI - Islet amyloid polypeptide (IAPP). A short review. AB - The islet amyloid polypeptide (IAPP) was originally identified by chemical analysis of the amyloid component in a human pancreatic islet cell tumor. It consists of 37 amino acids and displays about 50% homology with the neuropeptide calcitonin gene-related peptide (CGRP). In the pancreatic islets the IAPP is confined to the beta-cells, co-stored with insulin in the secretory granules and apparently co-secreted with insulin on glucose stimulation. In beta-cell depletion states such as streptozotocin diabetes in animals and in human type I diabetes mellitus both the IAPP and the insulin levels display reduction or are even absent. Within the mature IAPP molecule the amino acid sequence 23-29 shows considerable amino acid heterogenicity among various mammalian species. The amino acid composition of human IAPP in this specific region promotes the development of pancreatic islet amyloidosis, a phenomenon related to the ability to develop type II diabetes in that particular species. However, as type II diabetes is an inherited disease affecting a subpopulation of humans, not only the gene coding mature IAPP, but also one or several other hereditary factors of unknown origin are needed for the disease to develop. We have established a radioimmunoassay for plasma measurements of IAPP. During screening investigations of a large material of endocrine tumors we found a patient with extremely elevated plasma levels of IAPP, about 20,000 pmol/l. Immunohistochemical investigations confirmed the IAPP content and also revealed amyloid deposits. While performing an oral glucose tolerance test insulin levels remained unchanged whereas there was an increase in the glucose and IAPP levels. It is thus concluded that IAPP can be used as a tumor marker in pancreatic islet cell tumors and that high plasma levels of IAPP can inhibit glucose stimulated insulin secretion. PMID- 1854503 TI - In situ hybridization for detection of hormone and peptide mRNA in carcinoid tumors. AB - In situ hybridization (ISH) is a widely used method to detect particular mRNA synthesizing cells. The method can be used to determine neuroendocrine properties of tumors by identifying the hormone and neuropeptide mRNA-producing tumor cells. Also, monitoring the production of particular mRNA under tumor progression or during certain therapies might be of prognostic value in the management of the tumor. In this paper are described methodological backgrounds and applications of the ISH method in detecting hormone and peptide mRNA in neuroendocrine tumors, especially midgut carcinoid. PMID- 1854504 TI - Diagnostic criteria of classical carcinoids. AB - The classical (mid-gut) carcinoids of the intestinal tract display a characteristic light microscopic morphology. However, sometimes intestinal tumours are seen resembling carcinoids and differential diagnostic difficulties arise. In the present study silver stains and immunoreactivities to chromogranin A + B, cytokeratins and epithelial membrane antigen (EMA) were evaluated as diagnostic adjuncts in six classical carcinoids and six intestinal carcinomas with carcinoid-like features. All classical carcinoids were argentaffin and argyrophil and contained a majority cell population with chromogranin immunoreactivity while only one carcinoid-like carcinoma was chromogranin immunoreactive and the stained cells in that case represented a minority of the tumour cell population. The cytokeratins were shown to be non-discriminatory. However, EMA expression occurred in five intestinal carcinomas and in the majority of the tumour cells of four of these cases, while only one classical carcinoid displayed a few EMA positive cells. Thus, silver stains in combination with chromogranin A + B and EMA appears to be of value to discriminate between classical carcinoids and carcinoid-like intestinal carcinomas. Further when intestinal carcinoids and carcinoid-like carcinomas are diagnosed with the aid of various tumour markers both qualitative and quantitative considerations must be made. PMID- 1854505 TI - Peptide hormones as tumor markers in neuroendocrine gastrointestinal tumors. AB - Since the development of the radioimmunoassay, the determination of serum or plasma levels of peptides has improved the diagnostic possibilities in neuroendocrine gastrointestinal and pancreatic tumors. Once the diagnosis of a carcinoid or an endocrine pancreatic tumor has been established the analyses of various peptides can help to characterize the tumor. Up till now there has been no 'screening' marker for the early detection of these tumors. The development of radioimmunoassay for analyses of chromogranins in plasma might imply such possibilities. In the management of the patients it is also important to have tumor markers that can give prognostic information. Recent findings might indicate that CA-50 could be an indicator of malignant disease and possibly also correlate with survival. PMID- 1854506 TI - Enterochromaffin-like cells and gastric argyrophil carcinoidosis. AB - The relevance of enterochromaffin-like (ECL) cells in gastric pathobiology has generated considerable interest particularly since the recent description of a pathological state characterized as gastric argyrophilic carcinoidosis. The morphological and biofunctional properties of these cells are distinct from other gastric endocrine cells. It is probable that ECL cells have a major role in the regulation of parietal cell function. Other possible functions may include a trophic regulatory influence. Of particular interest is the recent observation that agents which result in profound and sustained acid inhibition may cause ECL cell hyperplasia. This phenomenon has also been noted in human disease states in which a significant decrease in acid section is evident (pernicious anemia/atrophic gastritis). In patients with gastrinomas of the multiple endocrine neoplasia type I group, therapeutically induced acid inhibition may result in gastric ECL hyperplasia and even neoplasia (gastric carcinoid or ECLoma). Similarly, in the rodent species mastomys, which is genetically predisposed to the formation of gastric carcinoids, exposure to acid inhibitory agents results in rapid (90-120 days) development of gastric carcinoids. The pathobiological relevance of ECL cells and the mechanisms of their inducible hyperplasia and neoplasia may be of considerable significance in understanding the regulatory role of gastric endocrine cells. PMID- 1854507 TI - Carcinoid heart disease. A cardiologist's viewpoint. AB - In patients with malignant midgut carcinoid tumors, characteristic cardiac abnormalities can be demonstrated by cardiac ultrasound in 60-70%. These ultrasound findings include morphological and functional changes of the tricuspid and pulmonary valves, enlargement of the right heart cavities and paradoxical septal contraction pattern. In patients with severe carcinoid heart disease leading to right ventricular failure, reconstructive valvular surgery is of obvious beneficial value and should be considered when the malignant disease is under control and clinical signs of right heart failure cannot be managed medically. The pathognomonic carcinoid lesions are mainly located on the right side of the heart and consists microscopically of fibrous tissue superimposed on mural and valvular endocardium. Infiltration into underlying endocardium and myocardium has been demonstrated. The etiology of carcinoid heart disease remains obscure. The extent of the cardiac disease seems related to circulating tumor released substances such as serotonin and tachykinins. PMID- 1854508 TI - Treatment of malignant midgut carcinoid tumours with a long-acting somatostatin analogue octreotide. AB - Treatment with the somatostatin analogue octreotide, SMS 201-995 (Sandostatin), has been carried out in a series of 23 patients with malignant midgut carcinoid tumours. The patients received initially 50 micrograms twice a day for six months, thereafter a median of 100 micrograms twice daily. Six of 22 evaluable patients (28%) showed objective tumour response lasting for 6 to 30 months. Stable disease was observed in 8 of the 22 patients (36%) and progressive disease in a further 8 patients (36%). A subjective response with decrease of diarrhoea or flushing was noted in 11 out of 22 patients (50%). Two out of 6 patients with objective response demonstrated a significant decrease of tumour size lasting for 6 and 30 months respectively. In order to maintain the clinical response, the dose had to be increased in all 6 responders. The adverse effects included development of diabetic blood glucose levels in 8 out of 22 patients (36%). Albumin-modified serum calcium levels were significantly reduced after treatment with octreotide 50 micrograms twice a day. One patient developed symptoms of hypocalcemia which was reversed by supplementation with calcium and D-vitamins. The somatostatin analogue SMS 201-995 has a beneficial effect in the treatment of patients with the carcinoid syndrome. However, the precise role of the drug in the long-term management of these patients has to be further investigated. PMID- 1854509 TI - The role of interferons in the management of carcinoid tumors. AB - Malignant carcinoid tumors with the carcinoid syndrome has over the years presented a therapeutic challenge. Surgery is the treatment of choice in local disease but when liver metastases have developed other treatment procedures must be considered. Conventional chemotherapy has been of little benefit, whereas a new somatostatin analogue octreotide gives a good control of clinical symptoms but not of tumor progression. Interferon treatment was introduced in 1982 by our group and we are now presenting results of medical treatment in 130 patients with histologically verified malignant carcinoid tumors and liver metastases. One hundred and eleven patients were treated with alpha-interferon, whereas 19 patients received conventional chemotherapy. Forty-seven out of 111 patients (42%) treated with alpha-interferon demonstrated a significant biochemical response and 15% also more than 50% reduction of tumor size. In another 43 (39%) patients stabilization of the carcinoid disease was noted whereas 21 (19%) showed progressive disease. The median duration of response was 34 months. Subjective response with improvement of diarrheas, flush and/or bronchoconstriction was noticed in 76 patients (68%). Among the 19 patients treated with conventional chemotherapy only 2 showed biochemical response and it lasted only for 3-5 months. The patients treated with chemotherapy had a median survival of only 8 months compared with 80+ months in the group treated with alpha-interferon. The adverse reactions of alpha-interferon are manageable and consist mainly of fatigue, weight reduction and reduction of blood cell counts. Neutralizing interferon antibodies might occur in patients treated with recombinant alpha interferons (5-15%). PMID- 1854510 TI - Extended experience with recombinant alpha-2b interferon with or without hepatic artery embolization in the treatment of midgut carcinoid tumours. A preliminary report. AB - Thirty-six patients with histologically verified midgut carcinoid tumours and liver metastases were included in a prospective study with daily interferon therapy 5 x 10(6) IU s.c. for one or two years. All had the primary tumour removed at laparotomy, and whenever technically possible, an embolization of the hepatic arteries was performed prior to interferon start. Recombinant human alpha 2b interferon from Schering-Plough was employed. When interferon was given alone, 24% responded after one year, judged from a 50% reduction in excretion of 5 hydroxyindoleacetic acid in the urine. Three patients had died. Stable disease was found in 43%, while 19% progressed. Survival rate was 40% after 5 years from start of therapy. The median survival time from start of therapy was 3 years and 4 months. When embolization of the liver arteries had been performed prior to the start of interferon treatment, the response rate was 60% after one year, 20% had stable disease and 20% progressed. Survival rate was 75% up to 5 years of observation. We conclude that interferon is an effective treatment of malignant metastatic midgut carcinoid and that survival might be prolonged compared with historical controls. Embolization of the liver arteries seems to increase the response rate after one year. Kaplan-Meier plots suggest prolonged survival when interferon treatment is combined with embolization. PMID- 1854511 TI - Autoimmune phenomena in patients with malignant carcinoid tumors during interferon-alpha treatment. AB - Several previous reports suggest an association between treatment of patients with interferon-alpha (IFN-alpha) and development of autoantibodies and autoimmune disease. We here summarize the experience from a group of 135 patients with midgut carcinoid tumors treated with natural leukocyte IFN-alpha or recombinant IFN-alpha (rIFN-alpha). An unusual high incidence of antimicrosomal antibodies (MsAb) or anti-thyroglobulin antibodies (TgAb) and thyroid disease manifested as hyperthyroidism, hypothyroidism or a biphasic Hashimoto-like disease was seen, with female predominance. The incidence of antinuclear antibodies (ANA) was also increased, but equally in both sexes. Antibodies to parietal cells were found in 5 cases and 4 patients with pernicious anemia were detected. Two patients developed vasculitis of leukocytoclastic type and one a syndrome resembling systemic lupus erythematosus. Some patients treated with rIFN alpha develop anti-IFN antibodies. Such antibodies may also be autoantibodies reacting with autologous IFN-alpha. They can neutralize the biologic activity of administrated IFN preparation and cause therapeutic failure. The implications of the various autoimmune manifestations during IFN-alpha treatment are discussed. PMID- 1854512 TI - Abdominal surgery in patients with midgut carcinoid tumors. AB - In patients with midgut carcinoid tumors a curative, radical tumor removal should be attempted when possible. As these tumors are generally malignant, irrespective of size, the radical surgery implies that intestinal resection for excision of a primary tumor should be combined with an extended mesenteric resection. When the patients present with the carcinoid syndrome the disease is, with few exceptions, too advanced for curative surgery. However, surgery often has to be performed also in patients with the advanced carcinoids. Patients with more extensive disease may thus benefit from surgical debulking of large mesenteric or hepatic metastases. Moreover, when the patients present with abdominal symptoms it is important to exclude a threatening major abdominal complication, such as intestinal obstruction or ischemia. As these complications may cause malnutrition and deterioration, it is important to treat them properly, sometimes by repeated surgery. PMID- 1854513 TI - [Diagnostic exercise tests in adult men with no symptoms or with non-angina complaints]. AB - STUDY OBJECTIVE: to investigate clinical and ECG stress test differences in middle aged males either asymptomatic or with non-anginal symptoms and no previous myocardial infarction. DESIGN: retrospective stress data file analysis. SETTING: Outpatients at the stress test laboratory. PATIENTS: 296 consecutive patients referred to diagnostic treadmill testing from January-1988 to June-1989. RESULTS: no differences were found between symptomatic or asymptomatic individuals in the 17 variables analysed. CONCLUSIONS: despite the fact that patients with chest symptoms even if obviously non-anginal have an increased coronary disease prevalence when compared with age-matched asymptomatics, this difference seems to insufficient to be demonstrated by the ECG stress test results, making questionable the practical relevance of this symptomatic classification. PMID- 1854514 TI - [Stenosis of the common trunk with and without ostium involvement: clinical and angiographic characteristics]. AB - STUDY OBJECTIVE: To evaluate the clinical and angiographic profile of patients with left main coronary artery stenosis with (LM-OS) and without left coronary ostial stenosis (LM-NOS). DESIGN: Retrospective study of patients submitted to coronary angiography. SETTING: Laboratory of Hemodynamics and Interventional Cardiology at Bellvitge Hospital -Barcelona, Spain. PARTICIPANTS: 4663 consecutive patients (pts) with angiographically defined coronary artery disease. 139 pts had left main stenosis greater than or equal to 50%. Twelve pts were excluded because nonatheroesclerotic disease. Twenty two pts (17%), had LM-OS and 105 (83%) LM-NOS. INTERVENTIONS: Pts records were reviewed, to analyse the following clinical and angiographic variables: age, gender, risk factors to coronary artery disease, history of myocardial infarction, anginal class, presence of unstable angina, basal ECG ischemia, percentage and localization of left main stenosis, number and degree of vessels diseased, indexes of left ventricular function and coronary dominance. MAIN RESULTS: 1. Clinical characteristics--In the LM-OS group 18 pts were male and 4 female, while in the LM-NOS the numbers were respectively 90 and 15, p = ns. As for the gender the age showed also a similarity: 58 +/- 8 and 57 +/- 8 years, p = ns. A history of arterial hypertension was present in 73% of pts with LM-OS and 47% with LM-NOS, p greater than 0.05. With respect to the other clinical variables both groups were similar. The incidence of LM-OS was 0.4%. 2. Angiographic characteristics--The severity of left main stenosis was identical in the two groups: 80 +/- 15 in LM OS and 75 +/- 16% in LM-NOS (p = NS). Four (18%) of the pts with LM-OS had no associated coronary disease versus 7 (7%) of the LM-NOS (p = 0.08). There were 1.3 +/- 1 diseased vessels in the LM-OS group and 2.1 +/- 1 in the LM-NOS (p greater than 0.01). CONCLUSIONS: In the present series, the clinical and hemodynamic profile of patients with left main disease suggest that the following characteristics are more frequently seen in patients with ostial stenosis: 1) history of arterial hypertension; 2) no associated coronary disease; 3) smaller number of diseased vessels; 4) less significant stenosis. PMID- 1854516 TI - [Hemodynamic assessment after heart transplantation]. AB - OBJECTIVE: Comparative analysis of the results of the hemodynamic evaluations performed at the preoperative period, during the first week and at the end of the first and second years, after orthotopic heart transplantation. DESIGN: Retrospective study of hemodynamic evaluation of patients submitted to orthotopic cardiac transplantation from April 1987 to April 1990. SETTING: Transplanted patients admitted at the cardiology and cardio-toracic surgery departments of the Hospital Santa Marta. PATIENTS: 15 patients (eleven males and four females) aged 21 to 55 years (mean = 33.3 +/- 10.5), with the preoperative diagnosis: dilated cardiomyopathy in 11, ischemic heart disease in three and hypertrophic cardiomyopathy in one patient. All the patients were on triple immunosuppressive therapy (cyclosporine A, azatioprine and prednisolone) at the time of the first week evaluation. Three of the eight patients evaluated at the end of the first year were with double immunosuppressive regimen (without steroids), seven at NYHA functional class I and one patient at class II. The three patients evaluated at the end of the second year were on triple immunosuppressive regimen and in class I. INTERVENTIONS: We considered, preoperatively (PrOp), at the first week (1W), and at the end of the first (1Y) and second (2Y) years: mean right atrial pressure (RA), systolic pulmonary arterial pressure (PAs), mean pulmonary arterial pressure (PAm), pulmonary capillary wedge pressure (PCW), mean systemic arterial pressure (SAm), cardiac index (CI), pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR). At 1Y and 2y there were also considered the left ventricular end-diastolic pressure (LVEDP) and the ejection fraction (Ej). RESULTS: (table; see text) The results found at 2Y were similar to those showed at 1Y. At 1Y and 2Y LVEDP and Ej were normal. CONCLUSIONS: A high prevalence of mild to moderate hemodynamic disturbances characterizes the early post-operative period in cardiac transplantation. Abnormal pressures on right atrium, pulmonary artery, pulmonary capillary wedge pressure, are found on a significant number of patients, and pulmonary and systemic vascular resistances are also elevated. However at the end of the first year there is a significant improvement compared with the first week. Normality is the hallmark of hemodynamic evaluation performed in transplant recipients at the end of the first and second years. PMID- 1854515 TI - [Indirect criteria of coronary reperfusion and permeability in patients with acute myocardial infarction who have received thrombolytic therapy]. AB - OBJECTIVE: To evaluate the value of some indirect reperfusion signs (IRS) as markers of coronary artery patency in patients (PTS) with acute myocardial infarction (AMI) submitted to intravenous (IV) thrombolytic therapy (TT). DESIGN: Retrospective study, with analysis of the sensibility (S), specificity (SP) and predictive value (PV) of three IRS: 1. Pain and ST resolution in the first three hours; 2. Peak CK in the first 13 hours; 3. accelerated idioventricular rhythm (AIVR) in the first three hours. SETTING: Coronary Care Unit (CCU) of the Santo Antonio Hospital and Hemodynamic Laboratory of the S. Joao Hospital, Oporto. PATIENTS: Sixty seven PTS (mean age 53.4 +/- 10.6 years) with confirmed AMI, 62 male and five female, 34 with anterior and 33 with inferior infarction, TT started in the first three hours of the beginning of symptoms in 34 PTS and from three to six hours in 33 PTS, all submitted to coronary angiography in the hospital setting (7.6 +/- 5.9 days after AMI). INTERVENTIONS: IV administration of 1,500,000 U of streptokinase (SK) in 47 PTS and 30 U of APSAC in 20 PTS, preceded by 200 mg IV prednisolone and oral 100 mg acetilsalicylic acid, and followed by IV heparin therapy. Continuous electrocardiographic monitoring, and serial 12 leads ECG and enzymatic assays (at start and 1, 3, 7, 13 and 25 hours of TT). Analysis of the correlation of the three IRS (isolated and in association) with coronary artery patency (TIMI 2 or 3). MEASUREMENTS AND RESULTS: The total patency rate was 79.1%; there was no statistically significant difference with regard to AMI location, time of symptoms onset (0-3 vs 3-6 hours) or thrombolytic agent (SK vs APSAC). The first and second IRS had a high S and a low SP; together S = 79.2%, SP = 64.3% and PV = 89.4%. The third IRS with the first and/or the second one had a low S (about 25%) but SP and PV of 100%. The coronary patency rate of PTS without IRS was always greater than 50%. CONCLUSIONS: The analysed IRS although not very reliable are useful when considered in association. It is possible to assess PTA with high probability of reperfusion if AIVR is present. The absence of IRS does not exclude coronary artery patency. There is still missing more reliable no-invasive reperfusion markers. PMID- 1854517 TI - [Exercise test parameters after acute myocardial infarction. Relationship with coronary angiography]. AB - OBJECTIVE: To analyze the relation between characteristics of symptom-limited treadmill exercise stress test, after acute myocardial infarction (MI) and coronariographic results (number of diseased vessels). Both tests were performed before hospital discharge. DESIGN: Retrospective study with comparative analysis between variable defined groups. POPULATION AND SETTING: From 232 patients interned in the department of Cardiology of Hospital de Santa Marta with a first acute MI, a population of 112 patients submitted to exercise stress test and coronary angiography before discharge were selected (aged 29 to 69 years). METHODS: Symptom-limited treadmill exercise stress tests were performed according to Bruce protocol, with no heart-rate limitation. The following parameters were analyzed: Stress test duration (DUR); Double product variation (varDP); Metabolic equivalent units (METS); Maximal heart rate (FCmax); Percentage of the maximal reached heart rate (% FCmax); Incidence of ST segment depression (InfST); Maximal ST segment depression (Max-InfST); Onset minute of ST segment depression (MinInfST); Heart rate at the onset of ST segment depression (FCInfST); Double product at the onset of ST segment depression (DPInfST); Recovery minute of ST segment depression (MinRInfST); Onset minute of angina (MinAng); Heart rate at the onset of angina (FCAng); Double product at the onset of angina (DPAng). RESULTS: Statistical significant differences were obtained between coronariographic groups concerning the following parameters: DUR: 1-vessel/3 vessel P = 0.02; VarDP: 1-vessel/3-vessel p = 0.008, 2-vessel/3-vessel p = 0.004; METS: 1-vessel/3-vessel p = 0.01. No differences were seen between anterior and inferior myocardial infarctions regarding all the stress test parameters. However in patients with anterior MI significant differences were obtained concerning the following variables: VarDP: 1-vessel/2-vessel p = 0.02; InfraST: 1-vessel/2 vessel p = 0.006, 1-vessel/3-vessel p = 0.03; MaxInfST: 1-vessel/2-vessel p = 0.01, 1-vessel/3-vessel p = 0.0006; Angina: 1-vessel/2-vessel p = 0.0005, 1 vessel/3-vessel p = .001. In inferior myocardial infarctions only the stress duration differed between 1-vessel and 3-vessel groups (p = 0.003). CONCLUSIONS: Symptom-limited treadmill exercise stress tests, safely performed in our institution, were an important method for post MI evaluation and allowed the diagnosis of a great number of patients with residual ischemia. Statistical significant differences were found in ergometric parameters, between coronariographic groups (defined by the number of diseased vessels), emphasising the importance of stress tolerance analysis. PMID- 1854518 TI - [Primary heart tumors. Report of a clinical case]. AB - The authors describe the case of a 52-year-old patient with several hospitalizations due to acute pulmonary edema, clarified only during the performance of cardiac surgery for the correction of presumable mitral valvular pathology. A leiomiossarcome of the left auricle was concerned, which involved the posterior ring of the mitral valve, the interauricular septum and the orifices of the pulmonary veins. Due to the impossibility of proceeding with the complete resection of the tumor, the tumoral mass was wasted away in order to liberate the involved structures, this followed by chemotherapy. Two years since, the patient shows a generally deteriorated state, submitted to various hospitalizations due to cardiac insufficiency, having been objectivated hepatic metastization and recurrence of the primary neoplasm. PMID- 1854519 TI - [Acute dissection of the aorta with involvement of the right coronary artery and the aortic valve: report of a case]. PMID- 1854520 TI - How valid are responses to questions about behaviour in hypothetical illness situations? AB - Questions concerning the respondents' actions in response to hypothetical illnesses have been used in a number of studies of illness behaviour and health service utilization, but the answers obtained have never been validated by direct comparison with the respondents' behaviour during episodes of real illness. Five hundred and fifty-four questionnaires were returned by parents giving details of how they would respond to hypothetical episodes of cough, fever and sore throat in their children. During a two-month period of recording, the children suffered 78 episodes of one or other of these symptoms which led to a consultation. The aim of this study was to compare the parents' responses to the hypothetical situations in the questionnaire with what they said they had done before each of these consultations for real illness. The comparison concentrated on the intervals that parents waited before requesting consultations, and on their medication of their children. The parents' responses to the questionnaire were poor predictors of their reported behaviour during actual illness episodes. PMID- 1854521 TI - Consumers' views of the maternity services: implications for change and quality assurance. AB - The feasibility and usefulness of consumer surveys for quality assurance and planning maternity services were assessed in a postal survey of 1807 women in four health districts representing a range of social and demographic characteristics. A response rate of 79 per cent was achieved. Scope was identified for some reduction in length of stay: 43 per cent of postnatal women wished for a shorter stay than they have actually experienced. The Domino system and a 1-2 days stay were the preferred options (25 and 24 per cent respectively). Six per cent of postnatal women would have preferred a longer stay than experienced and consisted mainly of women with birth complications including caesarean deliveries, women with lack of help at home and Afro-Caribbeans. Schemes to increase continuity of care and make the delivery suite more home-like would be favoured by a large proportion of women. Sixty-five per cent of women regarded continuity of midwifery care and familiarity with the delivering midwife as important. Seventy-five per cent considered a home-like environment in the delivery suite as important, and gave specific suggestions of how this might be achieved. The results show that consumers' surveys are feasible, with a good response rate and range of views expressed by the study population. They can assist in monitoring quality and provide guidance for planning at local and regional levels. PMID- 1854522 TI - Communicable Disease Report October to December 1990. From the PHLS Communicable Disease Surveillance Centre. PMID- 1854524 TI - Rabies control. PMID- 1854523 TI - Associations between water quality and GIT symptoms in country dwellers. PMID- 1854525 TI - The problems of using multiple regression for modelling the demand, supply and use of health services. PMID- 1854526 TI - Smoking by adults in the European community: 1963 and 1987. PMID- 1854527 TI - The foetal and infant origins of inequalities in health in Britain. PMID- 1854528 TI - Changes in life and care in the year before death 1969-1987. AB - Studies based on random samples of adult deaths in 1969 and 1987 show that, although more people in the recent study were living alone in the year before they die (32 per cent compared with 15 per cent in the earlier study), there had also been an increase in the proportions living in institutions and being admitted to hospital in the 12 months before their death. More of those dying in 1987 than in 1969 had had a home help, whereas the proportion receiving care from district nurses was similar for the two studies and the amount of home visiting by general practitioners had fallen. A higher proportion of those dying of cancer in 1987 than in 1969 were thought to have known that they were dying (44 per cent against 16 per cent) and that they had cancer (73 per cent compared with 29 per cent). However, the proportion of relatives and others who thought the dying person's awareness, or lack of awareness, of the prognosis was 'best as it was' was lower for people dying of cancer in the more recent study (57 per cent against 69 per cent). The symptoms reported for those dying in 1969 and 1987 were generally similar but more of those who died in 1987 had suffered from mental confusion, depression and incontinence for a year or more. This reflects the increased age at which people were dying in the later study: longer life was sometimes associated with the prolongation of unpleasant symptoms. PMID- 1854529 TI - The pattern of childhood and related adult malignancies near Kingston-upon-Hull. AB - A study of childhood malignancies in North Humberside for 1974-1986 has revealed significant spatial aggregations. Though no specific reason was found, certain geographical areas, tumour groups and putative risks were identified for further study. One possible risk was a tin smelter to the west of Hull. A new method of analysis (Stone's conditional Poisson maximum) was used and showed some evidence of increased risk close to the smelter. This was accounted for by the solid tumours (primarily central nervous system malignancies) and was not apparent for the leukaemias. The Poisson maximum method is a special case of isotonic regression; a more general isotonic regression method, also due to Stone, Maximum Likelihood Ratio (MLR), is also available, and for reasons described elsewhere we prefer the more general method. The present study begins by applying this to the childhood data and then to data for corresponding adult disease (leukemias and central nervous system tumours) in the same area and time period. In both children and adults the results are negative for the leukaemias. For the remaining tumour categories, there is a significant increase in risk close to the smelter, but it is not possible to identify any aspect of the smelter or feature in its vicinity as causative. PMID- 1854530 TI - Setting up consensus standards for the care of patients in general practice. PMID- 1854531 TI - Medical confidentiality and records in general practice. PMID- 1854532 TI - Raising standards in family planning services. PMID- 1854533 TI - Prevention in general practice: the views of doctors in the Oxford region. AB - A postal questionnaire was sent to all 1291 general practitioners in the Oxford region to determine the pattern of preventive care and their beliefs about its effectiveness. Replies were received from 1014 doctors (79%). Doctors' attitudes to their role in prevention and health promotion were very positive and a large majority claimed to discuss health related topics with their patients when indicated. Fewer respondents said they made a point of discussing smoking habits (64%), alcohol intake (26%), diet (12%), or exercise (11%) as a matter of routine with all their adult patients. Most general practitioners said they usually offered simple advice, leaflets, or other aids when they had identified a problem, but few said they would refer these patients to the practice nurse. With the exception of cervical screening (45%), few respondents said they maintained statistics on the distribution of risk factors in their practice population. Despite considerable enthusiasm for their role in preventive health care, before the imposition of the new contact most general practitioners in the Oxford region had not yet embraced the model of prevention which the contract aims to encourage: systematic screening for risk factors and lifestyle advice for all patients. PMID- 1854534 TI - Two stage audit of cerebrovascular and coronary heart disease risk factor recording: the effect of case finding and screening programmes. AB - The level of recording of risk factors for cardiovascular disease by general practitioners in north east Scotland has been audited. The effect of the audit on recording levels has also been determined by means of a second audit one year later. Twenty four practices in Grampian took part in the study, each auditing a random selection of 100 records of male patients aged 35-64 years. The risk factors chosen were blood pressure, smoking habit, alcohol consumption, weight and height. Blood pressure was recorded in the majority of the records (68.0%) and the mean level of recording of all of the risk factors increased between the two audits. The increase in the recording of smoking habit, alcohol consumption and weight was statistically significant. Practices with organized systems of data collection had higher levels of risk factor recording than those without. The levels of recording achieved were thus dependent on factors that existed in the practices prior to the study. This suggests that to increase recording levels, future educational intervention should be aimed at changes of motivation. PMID- 1854535 TI - Development of an electronic prescription processing option: an aid for general practice. AB - An interactive computer-supported prescription processing system has been developed as an add-on to existing general practitioner information systems. The aim of the system is to improve the clarity, efficiency and economy of drug treatment choices and prescription writing. It enables the doctor to choose the best treatment from the system's formulary according to the patient's complaint, symptom or diagnosis. The selections are based on complaints and diagnoses from the International classification of primary care (ICPC). A prescription is printed and the potential exists for individualized patient instruction leaflets to be printed. Furthermore, the system may prove useful for retrospective and prospective statistical and epidemiological studies. This implies continuous adaptation, which is also necessary to keep the system updated. As well as an aid in daily general practice, the system is also designed to serve the needs of graduate and postgraduate training programmes. PMID- 1854536 TI - Teaching problem handling in general practice: a computer assisted learning software package for medical students. AB - A computer assisted learning software package for medical students, EnMesh, designed to increase understanding of the problem-handling skills needed in general practice has been developed at the University of Liverpool. Users access the system anonymously and respond in sequence to problems in the form of clinical vignettes. Responses to each problem, in the form of up to six two-line text statements, are generated by the user with a simple word processing facility. Users compare their responses with those of established general practitioners, searching for similar or matching ideas. After completing not less than four problems users are provided with feedback on their performance in relation to the physical, psychological and social dimensions of the problems. The frequency with which the system is being used and the results of self scoring are monitored by a parallel teacher programme. The programmes are designed to run on a wide range of microcomputers. EnMesh was designed to provide an informal learning resource within an established clinical course. The challenge of valid problems, the option to respond anonymously, self scoring and feedback on performance are features designed to attract student participation in computer assisted learning. Although in EnMesh the expert data is categorized in three dimensions, in designing such software the number of categories is limited solely by the range of responses which feedback is required to reflect. PMID- 1854537 TI - A survey of the health of British missionaries. AB - The results of medical examinations carried out on 212 missionary personnel from one missionary society returning on leave to the UK are presented. The great majority of missionaries worked in developing countries. They served in 27 countries altogether and for a total of 488 person years. The commonest illnesses reported overseas were malaria (87.3 per 1000 person years at risk), diarrhoea (63.5), anxiety (63.5), depression (41.0) and giardiasis (38.9). More illnesses were reported from West Africa (698 per 1000 person years at risk) than from any other region. Ten people (4.7%) were repatriated for health reasons and 10 relatives also returned as a consequence. Sixty per cent of those returning did so because of psychiatric illness. The highest rates of immunization achieved were for yellow fever (100% of those travelling to affected countries), tetanus (93%), polio (85%), typhoid (71%) and tuberculosis (53%). The results of urinalysis (100% of adults), full blood counts (78% of adults) and stool tests (74% of all people) are reported. The study shows that the history and psychiatric examination are an important part of the medical examination of people returning from overseas. Physical examination and urinalysis did not contribute much information, although the full blood count and absolute eosinophil count were useful tests. PMID- 1854538 TI - Breast screening: a subject for debate. AB - The National Health Service Breast Screening Programme was instituted in 1988 following the recommendations of the Forrest report in 1986. From the beginning it has been controversial. Is breast cancer screening efficacious? Can the efficacy produced in trials be reproduced nationwide in the UK? Do the benefits of screening outweigh the adverse effects? Answers to all these questions are not yet available but in the light of current evidence, breast screening does appear to offer a realistic opportunity to reduce the mortality from a disease which constitutes a major public health problem in the UK. The role of the general practitioner and the primary care team is considered in the light of the experience gained in the first phase of the screening programme. PMID- 1854539 TI - Use of antibiotics and antifungal agents in herpetic gingivostomatitis. PMID- 1854540 TI - Testicular self examination: evaluation of an educational leaflet. PMID- 1854541 TI - General practice at the coalface. PMID- 1854542 TI - MD theses from general practice. PMID- 1854543 TI - Videos in the waiting room. PMID- 1854544 TI - GPs for lesbians and gay men. PMID- 1854545 TI - Improving communication between the national general practice organizations. PMID- 1854546 TI - An enhanced outlet port clamp for blind patients on CAPD using the UVXD device. PMID- 1854547 TI - Direct measurement of pulmonary and systemic flow during assisted circulation. AB - During biventricular assistance as a bridge to cardiac transplantation, the flow data provided by the pumping systems were compared with flow data obtained with the Fick method. There was a difference between the data sets only in the first 20 hr of observation, with the Fick method giving higher values. During the same period, analysis of the arterial and pulmonary pressure traces showed pulsatile activity to be related with the electrocardiogram's T waves. In the long run, the flow data provided by both methods were no different and the T wave-related pulsatile activity disappeared. The authors concluded that the Fick method represents a useful tool when measuring total flow during biventricular support. PMID- 1854548 TI - The inhibition of calcification of bioprosthetic heart valves by Al and Fe pretreatment. PMID- 1854549 TI - Randomized clinical trials. PMID- 1854550 TI - The coming generation of new small vascular grafts. PMID- 1854551 TI - Biomaterials science, medical devices, and artificial organs. Synergistic interactions for the 1990s. PMID- 1854552 TI - Urea monitoring during dialysis: the wave of the future. A tale of two cities. AB - The National Cooperative Dialysis Study (NCDS) suggested that the removal of small molecules controls the adequacy of the dialysis prescription, and it would seem appropriate that renal units regularly carry out formal urea kinetic modeling to ensure that the adequacy of dialysis is provided. Current methods of calculating Kt/V (urea) are complex and require the accurate measurement of dialyzer urea clearance and calculation of the volume of distribution of urea. This may be done by the direct measurement of total urea removed or by the use of computer programs that examine plasma urea and weight changes over time. Both methods have inherent problems, and this has stimulated the search for easier "bedside" formulas for the calculation of Kt/V. These newer formulas involve examination of the percentage reduction in blood urea concentration during hemodialysis. Two such formulas were examined and applied to 78 patients undergoing hemodialysis in two centers. One center routinely carried out formal urea kinetic modeling; the other did not. In the first center, it was found that the majority of patients were receiving more dialysis than necessary to achieve Kt/V (urea) = 1 when the latter was judged by those formulas. This suggested the possibility of time savings, with considerable implications for cost efficiency. In the second center, the majority of patients required more dialysis. It was concluded that intermittent formal urea kinetic modeling tends to overshoot the necessary prescription to allow for occasional "imperfect" dialyses and also that it is impossible to base dialysis prescriptions on routine pre-dialysis blood work and a "feel" for patients' needs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854553 TI - ECMO in premature infants. Review of factors associated with mortality. AB - During the first few years of clinical research on neonatal extracorporeal membrane oxygenation (ECMO), 16 premature infants of less than 35 weeks gestational age were treated by the authors (RHB), and only four (25%) survived. Intracranial hemorrhage was common, prompting the authors to recommend that ECMO not be used in premature infants with respiratory failure. Since diagnostic methods, indications, and techniques of extracorporeal support have improved considerably, the records of these previous cases were reviewed in detail to determine if there was reason to believe that results might be better in the modern era. Of the 16 patients, four had pre-ECMO conditions that would now be considered contraindications and five of the remaining patients had major technical complications that are now rare. Anticoagulation and fluid management of these patients also would be handled much differently. Based on this review and on current experience with extracorporeal support in near-term infants, it is reasonable to expect that survival of moribund premature infants might be 50% or greater with extracorporeal support. New phase I trials using improved indications and technology are suggested. PMID- 1854554 TI - Evaluation of extracorporeal perfusion catheters using a standardized measurement technique--the M-number. AB - Cannulas used for extracorporeal circulating devices are made in many shapes and sizes. Side hole placement, length, and wall thickness can make the pressure-flow characteristics of catheters with similar French sizes quite different in their actual performance. A single value, the M-number, has been developed that describes the pressure-flow characteristics of an individual cannula. This number can be used to compare catheters and assess their potential utility for given bypass requirements. The M-numbers for commonly used catheters that are placed by extrathoracic dissections are determined. Clinical situations are presented that demonstrate applications of the M-number. PMID- 1854556 TI - Intraoperative determination of mediastinal constraints for a total artificial heart. AB - The anatomic constraints to mediastinal fit of a total artificial heart (TAH) were largely neglected during the early developmental stages, precipitating failure due to compression or torsion of intrathoracic conduits and vascular structures. Cadaveric studies quantifying anatomic constraints are limited by postmortem factors causing distortion of critical structures. This study defines the anatomic constraints and parameters necessary for designing an implantable TAH. Importantly, these parameters were measured in 12 consecutive patients undergoing orthotopic cardiac transplant (mean body surface area, 2.0 +/- 0.1 m2) after native heart amputation. A full sized contour model of the cylindrical TAH (diameter, 97 mm; width, 78 mm) was inserted into the pericardial cavity to verify fit, which was found adequate in each case, with no identifiable compression of adjacent vascular structures. Intraoperative measurements obtained define intrathoracic and pericardial constraints for a cardiac prosthesis (mean pericardial dimensions: length, 133.0 mm; width, 154.0 mm; depth, 129.0 mm). The parameters measured will provide useful reference for other prosthetic devices, since they were obtained intraoperatively rather than postmortem. The current dimensions of our TAH were found to be acceptable for orthotopic implantation. PMID- 1854555 TI - A comparative analysis of mass transport models in peritoneal dialysis. AB - To better understand the differences in published estimates of peritoneal mass transport coefficients, a comparative analysis of seven mathematical models of peritoneal transport was performed. Uniform investigation involving measurements of solute concentrations and accurate determination of peritoneal dialysate volume was undertaken in twenty-eight 6 hour dwell studies using 3.86% glucose dialysate in non-diabetic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The investigated models were all based on the theory of transport across a homogeneous membrane. Diffusive mass transport coefficients (KBD) calculated during a period of dialysate isovolemia served as reference values in the comparative analysis. The evaluation of models involved calculations of transport coefficients and comparison of calculated dialysate-to plasma concentration ratios (D/P) with experimental D/P. The best fit of theoretically predicted D/P to experimental D/P was obtained with Pyle-Popovich's model, which accounts for both the diffusive (KBD) and convective (sieving coefficient [S]) characteristics of the peritoneal membrane. Garred's model, assuming S = 1, yielded acceptable results for small solutes (except sodium), whereas Henderson's model, in which convective transport is neglected, proved to be surprisingly accurate for KBD for both small solutes (except sodium) and protein. S values (mean +/- SD) calculated using Pyle-Popovich's model were found to be out of the physically interpretable range for glucose (S = -0.38 +/- 0.48) and potassium (S = 1.57 +/- 0.19), and therefore these S values should be treated as phenomenologic rather than physical quantities. PMID- 1854557 TI - The effect of heparin on three whole blood activated clotting tests and thrombin time. AB - Whole blood activated clotting time (ACT) can be determined by many different methods that use a variety of clotting cascade activators and end-points. This study compared the results of three whole blood ACT instruments at equivalent concentrations of heparin. Whole blood (9.8 ml) from 10 healthy adult volunteers without coagulation abnormalities was added to 0.2 ml of heparin solution producing heparin concentrations of 0, 0.1, 0.2, 0.4, 0.6, 0.8, and 1.0 U/ml. Coagulation status was determined in duplicate with the Hemochron 400 System (HC), the HemoTec Automated Coagulation Timer (HT), and the TriMed ACTivator (TM). Thrombin times or dilutions (TT) were also determined for each sample. Baseline values did not differ (p greater than 0.05); however, the HT and TM ACT values were significantly longer (p less than 0.05) than the HC ACT values at predicted heparin concentrations greater than 0.2 U/ml. Results from the HT and TM instruments were not significantly different. The HT and TM instruments both provided a greater ACT range over the heparin concentrations tested. Of the tests studied to monitor heparin therapy, mean scaled TTs showed the best correlation with predicted heparin concentrations. PMID- 1854558 TI - [Psychiatric practice and dentistry: anthropological and clinical relations]. AB - The authors establish the clinical and anthropological connections relative to the buccal patient. Although apparently the relationship between the psychiatrist and the patient is diametrically opposite to the relationship that a buccolic professional may have with a patient, however, the reflexion which is developed in the work shows, from a wholistic and anthropological perspective, that both professional activities are confluent when dealing with the conception of "sick patient". Two clinical cases illustrate the difficulties which, sometimes, appear in the relationship between the psychiatrist and the ondotologist. PMID- 1854559 TI - [Osteoanthropology of the craniognathic system]. PMID- 1854560 TI - [Changes in vertical dimension in orthognathic surgery]. PMID- 1854561 TI - [The past and present of dentistry in Spain]. PMID- 1854562 TI - [Differential diagnosis of endoperio problems]. PMID- 1854563 TI - [Mucogingival surgery and root recovering (1)]. PMID- 1854564 TI - [Periapical odontogenic processes of inflammatory origin. Enzyme activity]. AB - A histoenzymological study was carried out on 40 tissues specimens removed at biopsy and for surgical operations of the following lesions: 5 normal oral mucosa, 5 periapical granulomas, and 30 periapical inflammatory cysts. The purpose of this study was to study some possibly significant variations in levels o activities of oxidative enzymes, and hydrolaxes enzymes. In inflammatory cysts, enzymatic activities were similar to normal epithelium. There was high levels of acid phosphatase LDH and G6PDH activity in the central cells of apical granulomas and in the exfoliating epithelial cells of periapical inflammatory cysts. There were differency in the glycosaminoglicans activity on the different epitelial pattern. PMID- 1854565 TI - HIV cardiomyopathy: a dark cloud with a silver lining? PMID- 1854566 TI - Thrombolytic treatment in acute myocardial infarction: neutrophil activation, peripheral leucocyte responses, and myocardial injury. AB - OBJECTIVE: To examine early leucocyte responses and neutrophil activation in acute myocardial infarction treated by streptokinase and to relate the findings to coronary recanalisation and indices of myocardial damage in order to provide further information about the role of neutrophils in the evolution of injury. DESIGN: Group analysis of paired blood samples, obtained before streptokinase treatment and one hour after it, and of three indirect measures of myocardial injury: left ventricular ejection fraction, QRS score, and peak creatine kinase. SETTING: The coronary care unit of a district general hospital. PATIENTS: 39 patients with acute myocardial infarction who underwent paired blood sampling (before streptokinase and one hour after streptokinase) and cardiac catheterisation 5 (3-8) days later. END POINTS: Changes in peripheral white cell and neutrophil counts and plasma elastase one hour after streptokinase infusion. Comparison of these variables in patients with and without patency of the infarct related coronary artery. Correlations between these variables and indirect measures of myocardial injury. RESULTS: Neutrophil activation, as reflected by plasma elastase, increased sharply one hour after streptokinase. Total white cell and neutrophil counts also increased. Changes tended to be more pronounced in patients with patency of the infarct related artery, though the trend was not statistically significant. Neutrophil activation before streptokinase was unrelated to indirect indices of myocardial injury but only one hour after streptokinase a weak negative correlation with left ventricular ejection fraction had developed. Peripheral neutrophil responses showed a similar relation to ejection fraction and also correlated with peak creatine kinase and QRS score. CONCLUSIONS: Thrombolytic treatment in acute myocardial infarction is associated with an abrupt reactive neutrophil response which provides an early measure of injury. It is also associated with neutrophil activation, probably in response to coronary recanalisation and myocardial reperfusion. Activated neutrophils are recognised as mediators of reperfusion injury in experimental infarction and the data in the present study provide preliminary evidence of a similar pathogenic role in the clinical setting. PMID- 1854567 TI - Cardiac catheterisation with 5 French catheters. PMID- 1854568 TI - A controlled trial of community based coronary rehabilitation. PMID- 1854569 TI - Aging, autonomic function, and the perception of angina. AB - OBJECTIVE: To determine the effects of age and autonomic function on the perception of angina. DESIGN: Prospective evaluation of the relations between anginal perceptual threshold, autonomic function, and systolic blood pressure in patients with symptomatic coronary artery disease. Statistical analysis was by non-parametric techniques. SETTING: Cardiology departments of a district general hospital and a post-graduate teaching centre. SUBJECTS: 82 non-diabetic men with typical exertional angina and coronary artery disease confirmed by arteriography (n = 64) or a history of Q wave infarction (n = 18). MAIN OUTCOME MEASURES: Age, anginal perceptual threshold, autonomic function, and blood pressure. Anginal perceptual threshold was defined as the time from onset of 0.1 mV ST depression to the onset of angina during treadmill stress testing. Autonomic function was measured as the ratio of peak heart rate during the Valsalva manoeuvre to the minimum rate after release. RESULTS: Anginal perceptual threshold showed a weak but significant correlation with age, with older patients tending to have a longer interval between the onset of ST depression and the onset of angina. Comparison of patients in the upper and lower quartile age ranges showed a difference of 50 seconds between median threshold measurements. Blood pressure and heart rate responses to the Valsalva manoeuvre also correlated with age, but neither variable correlated with the anginal perceptual threshold. CONCLUSIONS: In non-diabetic men with coronary artery disease the perception of angina tends to deteriorate with advancing age. The mechanism is unclear but is not attributable solely to alterations in blood pressure or autonomic function. PMID- 1854570 TI - Angiotensin converting enzyme inhibitors and magnesium conservation in patients with congestive cardiac failure. AB - OBJECTIVE: To investigate whether angiotensin converting enzyme inhibitors reduce diuretic induced magnesium excretion in patients in congestive cardiac failure. DESIGN: Cohort analytic study. SETTING: A London district general hospital. SUBJECTS: Thirty four patients with chronic congestive cardiac failure caused by ischaemic heart disease or cardiomyopathy selected consecutively from inpatients under the care of two consultant cardiologists. Nineteen patients (group 1) on diuretics alone were compared with 15 patients (group 2) taking diuretics plus either enalapril or captopril. All drug regimens were stable for at least three months before the study. Patients with impaired renal function (plasma creatinine greater than 120 mumol/l) were excluded. INTERVENTIONS: An intravenous loading dose of magnesium sulphate was given to minimise the variability in baseline magnesium state. MAIN OUTCOME MEASURE: Total urine magnesium excretion and creatinine clearance in 24 hour urine collections. RESULTS: Plasma magnesium was similar in the two groups. However, 24 hour urine magnesium excretion was significantly lower in group 2 than in group 1. Furthermore, creatinine clearance was also significantly lower in group 2 and correlated strongly with magnesium excretion. There was no such relation in group 1. There was no difference in fractional clearance of magnesium between groups. CONCLUSION: Angiotensin converting enzyme inhibitors have an important magnesium conserving action, possibly via their effect on glomerular filtration rate. PMID- 1854571 TI - Intracardiac mobile thrombus and D-dimer fragment of fibrin in patients with mitral stenosis. AB - OBJECTIVE: To investigate the relation between intracardiac thrombus and blood coagulability in patients with mitral stenosis. DESIGN: Prospective study. Cross sectional echocardiography and plasma concentrations of the D-dimer fragment of fibrin were used concurrently to detect intracardiac thrombus in patients with mitral stenosis. SETTING: Department of Medicine, National Cardiovascular Centre, Osaka, Japan. PATIENTS: 63 patients with mitral stenosis. None of them had been receiving any anticoagulants or antiplatelet agents. MAIN OUTCOME MEASURES: Plasma concentrations of D-dimer in patients with a mobile intracardiac thrombus, those in patients with a non-mobile intracardiac thrombus, and those in patients without an intracardiac thrombus. RESULTS: A mobile intracardiac thrombus was found in 10 patients and a non-mobile thrombus in eight. The remaining 45 patients had no intracardiac thrombi. Plasma concentrations of D-dimer in the 10 patients with a mobile thrombus were all greater than 300 ng/ml (mean 983.3, 95% confidence interval 498.9 to 1467.7 ng/ml) and they were significantly higher than those in the patients with a non-mobile thrombus (226.2, 33.6 to 418.8 ng/ml) and the patients without an intracardiac thrombus (147.2, 110.4 to 184 ng/ml). CONCLUSIONS: A high plasma concentration of D-dimer seemed to reflect a hypercoagulable intracardiac state and may be a helpful indicator of the possible presence of mobile intracardiac thrombus in patients with mitral stenosis. PMID- 1854572 TI - Familial Ebstein's anomaly: a report of six cases in two generations associated with mild skeletal abnormalities. AB - In a family of 11 persons in three generations six had Ebstein's anomaly. Five of the six showed mild skeletal anomalies--that is, restricted finger extension, with or without limitation of larger joints, and externally rotated little toes. Two other members of the family had the skeletal features without Ebstein's anomaly. The findings suggest a dominantly inherited syndrome of Ebstein's anomaly and skeletal abnormalities. The four female patients were all mildly affected whereas three of the four male patients were severely affected. PMID- 1854573 TI - Influence of racial origin on admission rates of patients with suspected myocardial infarction in Birmingham. AB - All patients with suspected myocardial infarction admitted to hospital in four Birmingham health districts were studied to test the hypothesis that Asian patients would be overrepresented and Caribbean patients underrepresented compared with the indigenous population. One thousand four hundred and ninety six patients had a final diagnosis of myocardial infarction or severe angina pectoris. The relative risk of admission for Asian men compared with white men aged 45-64 years was 2.65 (95% confidence interval 2.20 to 3.19) and the risk for Asian men was high for both myocardial infarction and ischaemia when analysed separately. The relative risk of admission for Caribbean men compared with white men was 0.53 (95% CI 0.33 to 1.20). The relative risk for Asian women compared with white women in the same age group was 2.58 (95% CI 1.68 to 3.96), but this was due to an excess of admissions diagnosed as ischaemia rather than infarction in the Asian women. For Caribbean and white women the risk of admission was the same, although significantly fewer Caribbean women were admitted with myocardial infarction. The study was undertaken in 1986-87 and population data had to be derived from the 1981 census. The resident population changed in those five years and so the results were recalculated making allowances for these changes in the health districts involved. Based on these data the admission rate for Asian men with suspected myocardial infarction aged 45-64 was nearly twice that for white men (1.8): the relative risk of admission for Asian men compared with white men was 2.04 (95% CI 1.53 to 2.18). For Caribbean men the relative risk compared with white men was 0.45 (95% CI 0.29 to 0.71). For Asian women the relative risk of admission calculated from the adjusted census data resemble that in white women aged 45-64 years. The relative risk for admission with coronary heart disease in Asians is higher than expected work; one possible explanation for this is that the Asian population resident in the area under study was larger than estimated. The single major difference in risk factors was the high prevalence of diabetes mellitus in Asians (19.5% compared with 8.3% for white residents) but this did not wholly account for the excess of admissions from the Asian community. PMID- 1854574 TI - Outcome of extensive coronary artery dissection during coronary angioplasty. AB - A total of 32 (3.6%) patients of 880 undergoing coronary angioplasty during a nine year period at one hospital had extensive dissection (defined as a dissection extending beyond the limits of the dilated angioplasty balloon) in the coronary artery in which the angioplasty procedure was performed. Two (6.25%) of the 32 patients (both of whom were undergoing angioplasty because of unstable angina that was refractory to medical treatment) died as a consequence of the coronary artery dissection. Twelve (38%) needed immediate coronary artery bypass surgery and 11 (34%) had a myocardial infarction, which in four was minor in extent. During follow up, 20 of the 32 patients were successfully managed by medical treatment; only two needed further angioplasty procedures. There were no late deaths. Extensive coronary artery dissection is a serious complication of coronary angioplasty, with a high early mortality and a high incidence of infarction and requirement for bypass surgery. None the less, patients with extensive dissection who are free from the manifestations of acute ischaemia at the end of the procedure can be managed conservatively and have a good immediate and medium term outlook. Attempts should be made to stabilise extensive dissection during coronary angioplasty so that surgical intervention can be delayed or avoided altogether if possible. PMID- 1854575 TI - Percutaneous laser valvotomy with balloon dilatation of the pulmonary valve as primary treatment for pulmonary atresia. AB - A neonate with pulmonary atresia and an intact ventricular septum with a tripartite right ventricle was successfully treated by percutaneous balloon dilatation of the pulmonary valve. This was facilitated by previous laser valvotomy with a hot tip Trimedyne laser wire. There were no major complications. Four weeks later the patient was discharged home on no medication with peripheral oxygen saturations of 70% in air. PMID- 1854576 TI - Proceedings of the British Cardiac Society. Glasgow, 30 April-3 May 1991. Abstracts. PMID- 1854577 TI - Plasma endothelin in coronary venous blood from patients with either stable or unstable angina. AB - STUDY OBJECTIVE: To test the hypothesis that the active coronary endothelial lesions in unstable angina raise the endothelin concentration in coronary venous blood. DESIGN: Systemic and coronary venous blood samples were obtained from unselected patients with the clinical syndromes of either stable or unstable angina at the time of cardiac catheterisation and coronary arteriography. Control venous blood samples were obtained from healthy laboratory workers and from patients with chronic renal failure treated by intermittent haemodialysis. PATIENTS: Twelve patients with angina: seven with stable symptoms and five with unstable angina. RESULTS: The mean coronary venous endothelin concentration in unstable angina was 2.32 ng/l (range 1.7-3.2 ng/l). In stable angina it was 2.77 ng/l (range 2.1-4.4 ng/l). These values were not significantly different from one another nor from the values obtained in systemic venous blood from either group or from the healthy controls. Circulating endothelin concentrations were much higher in venous blood from the patients treated by haemodialysis. CONCLUSIONS: These data do not support the hypothesis that raised endothelin concentrations in coronary blood in patients with unstable angina may modulate variations in coronary arterial tone thereby contributing to the clinical syndrome of chest pain and electrocardiographic changes at rest. The raised endothelin concentrations seen in systemic venous blood after myocardial infarction may be part of the systemic response to myocardial infarction. PMID- 1854578 TI - [Some considerations in relation to the biological dimension of the periodontium. Synonyms: biological width--biological space]. PMID- 1854579 TI - [Basic characteristics of the University of Antioquia Dental School in the context of other dental education institutions]. PMID- 1854580 TI - [Prosthetic-periodontal relations]. PMID- 1854581 TI - [Evaluation of etiological factors in relation to myofascial pain dysfunction syndrome. Clinical study of 100 students of the University of Antioquia Dental School]. PMID- 1854582 TI - [Rapid palatal expansion]. PMID- 1854583 TI - [Radiographic comparison of changes in apical lesions of teeth treated with conventional endodontics and with calcium hydroxide (Dycal)]. PMID- 1854584 TI - A brief history of iron metabolism. AB - A concise history of selected aspects of iron metabolism is presented. According to present understanding, the element is known to be required for transport and reduction of O2, for reduction of CO2, N2 and ribonucleotides, and for other essential cellular processes. The contributions of pioneers in the field, preeminent among them the cell physiologist and biochemist Otto Warburg, are recounted. PMID- 1854586 TI - Regulation of plasmid-mediated iron transport and virulence in Vibrio anguillarum. AB - Iron is essential for bacterial growth and metabolism. In vertebrates this metal is complexed by high-affinity iron-binding proteins, such as transferrin in serum. The fish pathogen Vibrio anguillarum possesses a very efficient iron uptake system which is encoded in the virulence plasmid pJM1. This allows the bacterium to utilize the otherwise unavailable iron in the fish host, resulting in the septicemic disease vibriosis. This system includes the siderophore anguibactin and transport components. We have cloned this iron-uptake system and have defined several genetic units by transposition mutagenesis. Nucleotide sequence analysis identified four open reading frames in the transport region, one of these corresponding to the gene for the outer membrane protein OM2 and another to a 40-kDa polypeptide. Complementation analysis indicated that products from all four reading frames are required for the transport of iron-anguibactin complexes. We have also identified positive and negative-acting regulatory elements that modulate in concert the expression of anguibactin biosynthetic genes and iron transport. The deletion or mutation of the positive-acting regulatory genes results in an iron-uptake-deficient phenotype and leads to an attenuation of virulence, underscoring the importance of this iron-uptake system as a virulence attribute of V. anguillarum. PMID- 1854585 TI - Transport of iron across the outer membrane. AB - The TonB protein is involved in energ-coupled receptor-dependent transport processes across the outer membrane. The TonB protein is anchored in the cytoplasmic membrane but exposed to the periplasmic space. To fulfill its function, it has to couple the energy-providing metabolism in the cytoplasmic membrane with regulation of outer membrane receptor activity. Ferrichrome and albomycin transport, uptake of colicin M, and infection by the phages T1 and phi 80 occur via the same receptor, the FhuA protein in the outer membrane. Therefore, this receptor is particularly suitable for the study of energy-coupled TonB-dependent transport across the outer membrane. Ferrichrome, albomycin and colicin M bind to the FhuA receptor but are not released into the periplasmic space of unenergized cells, or tonB mutants. In vivo interaction between FhuA and TonB is suggested by the restoration of activity of inactive FhuA proteins, bearing amino acid replacements in the TonB box, by TonB derivatives with single amino acid substitutions. Point mutations in the fhuA gene are suppressed by point mutations in the tonB gene. In addition, naturally occurring degradation of the TonB protein and its derivatives is preferentially prevented in vivo by FhuA and FhuA derivatives where functional interaction takes place. It is proposed that in the energized state, TonB induces a conformation in FhuA which leads to the release of the FhuA-bound compounds into the periplasmic space. Activation of FhuA by TonB depends on the ExbBD proteins in the cytoplasmic membrane. They can be partially replaced by the TolQR proteins which show strong sequence similarity to the ExbBD proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854587 TI - Characteristics of the interaction of the ferritin repressor protein with the iron-responsive element. AB - The iron-responsive regulation of ferritin mRNA translation is mediated by the specific interaction of the ferritin repressor protein (FRP) with the iron responsive element (IRE), a highly conserved 28-nucleotide sequence located in the 5' untranslated region of ferritin mRNAs. The IRE alone is necessary and sufficient to confer repression of translation by FRP upon a heterologous message, chloramphenicol acetyltransferase, in an in vitro translation system. The activity of FRP is sensitive to iron in vivo. Cytoplasmic extracts of rabbit kidney cells show reduction of FRP activity when grown in the presence of iron, as detected by RNA band shift assay. Using a nitrocellulose filter binding assay to examine the interaction of FRP with the IRE in more detail, we find that purified FRP has a single high-affinity binding site for the IRE with a Kd of 20 50 pM. Hemin pretreatment decreases the total amount of FRP which can bind to the IRE. This effect is dependent on hemin concentration. Interestingly, the FRP which remains active at a given hemin concentration binds to the IRE with the same high affinity as untreated FRP. A variety of hemin concentrations were examined for their effect on preformed FRP/IRE complexes. All hemin concentrations tested resulted in rapid complex breakdown. The final amount of complex breakdown corresponds to the concentration of hemin present in the reaction. The effect of hemin on FRP activity suggests that a specific hemin binding site exists on FRP. PMID- 1854588 TI - Ferritin mRNA probed, near the iron regulatory region, with protein and chemical (1,10-phenanthroline-Cu) nucleases. A possible role for base-paired flanking regions. AB - Iron stimulates ferritin synthesis in whole cells and animals, by increasing the entry of ferritin mRNA into polyribosomes. Dissection of the regulation at the molecular level has identified a 28-nucleotide, conserved, regulatory sequence (IRE = iron regulatory element) in the 5' non-coding region of ferritin mRNAs, plus trans-acting factor(s), one of which is a 90-kDa protein. The site of iron action is not entirely characterized but may involve heme; sequences in the 3' non-coding region of ferritin mRNA can modulate regulation. Ferritin mRNA is the first eukaryotic mRNA for which a conserved regulatory sequence and regulator protein have been identified. The same RNA-protein motif is used, through iron dependent degradation of transferrin receptor mRNA, to decrease synthesis of the receptor and cellular iron uptake. The regulatory structure of the transferrin receptor mRNA is composed, in part, of five copies of the IRE in the 3' non coding region. IRE structure, probed by cleavage with RNases T1, V1, 1,10 phenanthroline-Cu or modification with dimethyl sulfate, is a hairpin loop with conformational variations dependent on magnesium; a base-paired region flanking the IRE is also structurally sensitive to magnesium. Similar results were obtained with a synthetic 55-mer containing the IRE and with a full-length in vitro transcript with a G----A substitution in the loop.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854589 TI - Augmentation of antitumor effect on syngeneic murine solid tumors by an interleukin 2 slow delivery system, the IL-2 mini-pellet. AB - We evaluated the antitumor effect of an interleukin 2 (IL-2) slow delivery system, the IL-2 mini-pellet, in two murine solid tumor models, and also investigated the enhancement of its therapeutic effect by serial administration. The IL-2 mini-pellet contains 1 x 10(6) units of IL-2 and releases it slowly in vivo. In our experiment, the IL-2 mini-pellet was administered subcutaneously near the tumor site in combination with the intravenous injection of lymphokine activated killer (LAK) cells. When this regimen was given on days 8 and 11 after the subcutaneous inoculation of Meth A fibrosarcoma into BALB/c mice, tumor growth was significantly inhibited (p less than 0.05) compared to tumor growth in untreated controls. Moreover, the IL-2 mini-pellet alone was also effective in inhibiting tumor growth. In another experiment, MH134 hepatoma was inoculated into C3H/He mice. Both administration of the IL-2 mini-pellet alone and in combination with LAK cells resulted in complete tumor regression in four of five mice. In a third experiment, serial administration of the IL-2 mini-pellet at 3- or 5-day intervals prolonged the suppression of Meth A fibrosarcoma growth in BALB/c mice. These results suggested that the IL-2 mini-pellet could be applied to cancer immunotherapy and that its antitumor effect could be prolonged by serial administration. PMID- 1854590 TI - Inhibition of growth of rat hepatoma by local injection of liposomes containing recombinant interleukin-2. Antitumor effect of IL-2 liposome. AB - Human recombinant interleukin-2 (IL-2) was entrapped in liposome, consisting of egg phosphatidylcholine (PC) and cholesterol. The peri-tumor injections of IL-2 liposome inhibited significantly the growth of solid tumor and prolonged the survival time of rats with solid tumors which were induced by a subcutaneous (s.c.) inoculation of AH-66 cells. Immunohistochemical staining of peritoneal exudate cells and tumor tissues revealed a marked accumulation of activated macrophages in and around the tumor tissues induced by the local injections of IL 2 liposome. PMID- 1854591 TI - In vitro modulation of canine polymorphonuclear leukocyte function by granulocyte macrophage colony stimulating factor. AB - Granulocyte-macrophage colony stimulating factor (GMCSF) promotes the growth of granulocytes and macrophages from undifferentiated bone marrow cells and modulates the oxidative responses of polymorphonuclear leukocytes (PMN) to endogenous chemoattractants. We found that, in vitro, naturally occurring glycolsylated human GMCSF does not disturb the resting canine PMN membrane potential, may attentuate PMN oxidative responses to PMA, and is, to a small degree, chemotaxigenic. GMCSF, however, inhibits PMN chemotaxis to zymosan activated plasma (ZAP). Compared to temperature controls, GMCSF (1-100 U/ml) produced up to 1.5-fold increases in H2O2 production after 15 minutes, while phorbol myristate acetate (PMA) treated cells increased H2O2 production 8-12-fold after 15 minutes. Preincubation of cells with GMCSF (1-100 U/ml) prior to PMA stimulation significantly reduced the H2O2 levels induced by PMA. H2O2 production was inhibited up to 15% after 15 minutes of GMCSF preincubation and up to 40% after 60 minutes of preincubation. As a chemotaxigenic agent, GMCSF (10-1000 U/ml) was able to elicit 49%-102% increases in quantitative cellular migration, compared to random migration. Total cellular chemotaxis to GMCSF was less than 30% of the response to ZAP. Preincubation of PMNs with GMCSF for 15 minutes significantly inhibited ZAP-induced cellular migration. Human GMCSF does not appear to activate canine PMN in vitro and may actually down-regulate PMN inflammatory responses. PMID- 1854592 TI - The effect of photosensitive dye platonin on juvenile rheumatoid arthritis. AB - Two children with juvenile rheumatoid arthritis (JRA) were given photosensitive dye Platonin in combination with prednisolone. Analysis of clinical and laboratory data showed that Platonin was efficacious in the improvement of the clinical symptoms and the severity of inflammation, or in the maintenance of the remission state. There were no adverse side effects during long-term administration of medication. PMID- 1854593 TI - A regimen of surgical adjuvant immunotherapy for cancer with interleukin 2 and lymphokine-activated killer cells. Basis, clinical toxicity, and immunomodulatory effects. AB - We designed a unique regimen of adoptive immunotherapy with lymphokine-activated killer (LAK) cells and recombinant interleukin 2 (rIL-2) for application with surgical adjuvant therapy of cancer. The regimen features the prolonged (6 consecutive days) s.c. administration of low-dose rIL-2 and the transfer of ex vivo generated LAK cells from regional lymph node lymphocytes, obtained at the time of surgical operation. According to this regimen, 5 patients with primary lung cancer received immunotherapy about 2 weeks after surgery (pulmonary lobectomy). Clinical toxicities included fever(5/5), fatigue(5/5), slight(less than 5%) weight gain(5/5), increase of pleural effusion at the lobectomy site(2/5), and edema formation(1/5). All toxicities reversed within 4 days after the completion of therapy. Rebound lymphocytosis after therapy ranged from 2.4 to 5.5-fold (mean, 4.3-fold) over the baseline. Peripheral blood lymphocytes obtained during this lymphocytosis exhibited in vitro LAK activity in 4 of 5 patients. Thus, the regimen is considered to be well-tolerable and immunologically active in regard to the postoperative state of the patients. PMID- 1854594 TI - BLT-esterase activity following in vitro and in vivo activation of human lymphocytes with interleukin-2. In vivo IL-2 induces BLT-esterase. AB - BLT-esterase and cytolytic activity by human in vitro and in vivo generated Lymphokine Activated Killer (LAK) cells were measured. Lysates made from peripheral blood lymphocytes (PBL) of both normal donors and cancer patients receiving IL-2 therapy were assayed for BLT-esterase activity in a spectro photometric assay. Cytotoxicity of PBL was measured in a 51Cr-release assay. Both BLT-esterase activity and cytotoxicity increased when normal-donor PBL were stimulated in vitro with IL-2, with greater activities at higher IL-2 concentrations. The activities also increased over time, peaking at 6 days of in vitro stimulation. Patient PBL had increased BLT-esterase and cytotoxic activities after 4 weeks of in vivo IL-2 treatment. This association of BLT esterase activity and cytotoxicity with IL-2 activation is consistent with the model that LAK cytotoxicity is mediated by secretion of BLT-esterase associated cytolytic granules. Lymphocytes obtained after in vivo IL-2 treatment and cultured for 3-4 hours in IL-2 show markedly augmented cytotoxic activity but no increase in their BLT-esterase activity. These results indicate that the increased cytotoxicity observed after this brief pulse of in vitro IL-2 following in vivo IL-2 treatment must result from effects of IL-2 other than the production of more esterase-containing cytolytic granules. PMID- 1854595 TI - Atherosclerosis: cellular aspects and potential interventions. AB - The pathogenesis of atherosclerosis has been extensively studied and the cellular aspects increasingly characterized. This review will focus on the basic pathology, presumed cellular events, cellular interactions, cell-lipid relationships, and potential therapies of atherosclerosis. Fatty streaks, fibrous plaques, and complicated plaques are the pathologic hallmarks of atherosclerosis. These lesions insidiously progress, and symptoms appear to develop when the plaque luminal surface destabilizes. The major cellular contributors to plaque development are monocytes/macrophages, endothelial cells, smooth muscle cells, and, to a lesser degree, lymphocytes and platelets. They interact in a complicated fashion. Growth factors and cytokines produced by these cells are also of great importance for cell-cell interaction. Hemodynamic factors contribute to atherogenesis at preferential sites within the arterial vasculature, presumably by effects on the cellular mechanisms. Hyperlipidemia, especially elevations of total and LDL-cholesterol, has been well characterized as an atherosclerotic risk factor. Cellular modification of LDL-cholesterol, primarily by oxidation, leads to more rapid uptake by macrophage-derived foam cells, enhancing plaque growth by this and other mechanisms. These observations may unify the cellular and lipid contributors to atherogenesis. Therapies directed at the cellular contributors to atherosclerosis are being assessed. Dietary n-3 fatty acid supplementation reduces the extent of experimental atherosclerosis, and human studies are in progress. Many potential cellular effects of n-3 fatty acids have been demonstrated. Other potential therapies for atherosclerosis that probably work at the cellular level include calcium channel blockers, antioxidants, and heparinoids. An exciting new era of atherosclerosis research and, hopefully, therapy has dawned, as knowledge about its cellular basis accrues. PMID- 1854596 TI - Monosialoganglioside GM1 in cerebral ischemia. AB - In vitro studies have shown that monosialoganglioside GM1 reduces excitatory amino acid-related neurotoxicity by limiting the downstream consequences of abusive excitatory amino acid receptor stimulation, while enhancing neuronotrophic factor action in a variety of neuronal cell types. Systemic administration of GM1 appears to be efficacious in reducing acute nerve cell damage and in facilitating medium- and long-term functional recovery after brain injury. Although the mechanism of action remains unclear, it appears likely that GM1 protective effects in the acute injury phase are at least in part due to the attenuation of excitotoxicity, while the long-term functional recovery might reflect GM1 potentiation of neuronotrophic factors. The potential therapeutic efficacy of GM1 administration in different conditions in humans, as suggested by pioneer clinical studies, is reviewed. Further larger, randomized, double-blind clinical studies are necessary to define the therapeutic efficacy. PMID- 1854597 TI - Thrombolytic therapy for stroke. AB - Thrombolytic therapy has recently been shown to be beneficial in the setting of acute myocardial infarction, and thrombolysis resulting in vascular recanalization has been achieved in several other human disease states, including stroke. Advances in the understanding of the fibrinolytic system have led to the development of several new and distinctive thrombolytic strategies. Animal studies of stroke have been encouraging with regard to arterial recanalization and safety. Clinically, the availability of brain computed tomography has allowed pilot studies to proceed by providing rapid identification of patients with nonhemorrhagic stroke. Arterial recanalization has been demonstrated in patients with ischemic stroke following the administration of any one of several thrombolytic drugs. Placebo-controlled trials have not been completed, and so clinical benefit has not been established. Even though the development of brain hemorrhage has been an infrequent complication, the very high morbidity and mortality have been worrisome. Ironically, thrombolytic therapy holds promise for treatment of subarachnoid hemorrhage and perhaps also for spontaneous intracerebral hemorrhage. Human studies have been limited, but complications have been modest, and clinical outcomes have been encouraging. PMID- 1854598 TI - Escherichia coli O157:H7 and its significance in foods. AB - Escherichia coli O157:H7 was conclusively identified as a pathogen in 1982 following its association with two food-related outbreaks of an unusual gastrointestinal illness. The organism is now recognized as an important cause of foodborne disease, with outbreaks reported in the U.S.A., Canada, and the United Kingdom. Illness is generally quite severe, and can include three different syndromes, i.e., hemorrhagic colitis, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Most outbreaks have been associated with eating undercooked ground beef or, less frequently, drinking raw milk. Surveys of retail raw meats and poultry revealed E. coli O157:H7 in 1.5 to 3.5% of ground beef, pork, poultry, and lamb. Dairy cattle, especially young animals, have been identified as a reservoir. The organism is typical of most E. coli, but does possess distinguishing characteristics. For example, E. coli O157:H7 does not ferment sorbitol within 24 h, does not possess beta-glucuronidase activity, and does not grow well or at all at 44-45.5 degrees C. The organism has no unusual heat resistance; heating ground beef sufficiently to kill typical strains of salmonellae will also kill E. coli O157:H7. The mechanism of pathogenicity has not been fully elucidated, but clinical isolates produce one or more verotoxins which are believed to be important virulence factors. Little is known about the significance of pre-formed verotoxins in foods. The use of proper hygienic practices in handling foods of animal origin and proper heating of such foods before consumption are important control measures for the prevention of E. coli O157:H7 infections. PMID- 1854599 TI - Aeromonas and Plesiomonas as food- and waterborne pathogens. AB - Aeromonas and Plesiomonas have become increasingly recognized as human enteropathogens. Plesiomonas shigelloides has mainly been recovered from various sea foods, whereas Aeromonas sp. have also been cultured from pigs, broilers, eggs, milk and vegetables. Aeromonas sp. also multiply rapidly at +4 degrees C which is a significant risk in food storage. Aeromonas sp. have furthermore been recovered from fresh water sources, and some isolates are resistant to chlorination which makes it a further risk factor. No large food- or waterborne outbreaks have been reported so far with Aeromonas sp. Various virulence factors involved in intestinal infections are described such as enterotoxins, cytotoxins, and adhesins. PMID- 1854600 TI - Detection of Clostridium perfringens type A enterotoxin in faecal and food samples using immunomagnetic separation (IMS)-ELISA. AB - A simple, rapid and sensitive immunoassay, based on immunomagnetic particles (Dynabeads M-280) was developed for detection and quantitation of Clostridium perfringens type A enterotoxin from faecal and food extracts. The assay had a detection limit of 2.5 ng/ml enterotoxin in homogenates of faeces and inoculated meat extracts. The specificity was confirmed by both crossed immunoelectrophoresis and Western immunoblotting techniques, using a purified enterotoxin as standard. PMID- 1854601 TI - Bioluminescence as a real-time monitor of injury and recovery in Salmonella typhimurium. AB - Bioluminescence provides a novel tool with which to probe in real time the recovery of microorganisms such as Salmonella typhimurium from sub-lethal injury, a condition of immense importance in the enumeration of microorganisms in food and environmental samples such as from estuarine waters. We describe the application of in vivo bioluminescence to monitor the recovery of S. typhimurium from freeze injury and, in addition, we explore the effect of multiple stress conditions on microbial recovery where we compare bioluminescence with viable count measurement. PMID- 1854602 TI - Detection of Escherichia coli and identification of enterotoxigenic strains by primer-directed enzymatic amplification of specific DNA sequences. AB - The polymerase chain reaction (PCR) was used to amplify DNA sequences from the malB operon of Escherichia coli. All E. coli strains tested yielded the specific DNA fragment. No amplification products were obtained with other Enterobacteriaceae. E. coli strains which produce enterotoxins were identified with additional primer pairs specific for the genes coding for the heat-labile toxin type I (LTI) and the heat-stable toxin type I (STI). Amplification products were identified by DNA-DNA hybridization. Alternatively, restriction endonuclease analysis was used for identification and to distinguish between different alleles of the enterotoxin genes. The detection limit was 10 bacteria. The PCR systems were validated by testing 27 E. coli of known enterotoxigenic properties. The PCR results were consistent with factual toxin production as determined by immunoassays. In addition, 58 E. coli strains isolated from soft cheese and mayonnaise were analyzed by PCR. One strain from a cheese sample was found to have the genetic information for STI production. This strain produced STI as determined by enzyme-linked immunosorbent assay. PMID- 1854603 TI - Italian experience in Salmonella enteritidis 1978-1988: characterization of isolates from food and man. AB - Salmonella enteritidis accounted for 5.45% of the 118.685 Salmonella isolates from man and for 2.65% of the 3.315 Salmonella isolates from food in Italy in the eleven year period 1978 to 1988. In the years 1978-1982 no S. enteritidis strain was isolated from eggs and poultry; in the years 1983-1988 the 53% of S. enteritidis isolates from food were from eggs and poultry. In 1989 S. enteritidis accounted for 744 isolates from man and 22 from food of which 80% were from eggs and poultry (partial data). In that year 18 outbreaks caused by S. enteritidis were reported to the National Centre of Enteric Pathogens in Rome. Characteristics of 81 S. enteritidis isolates were examined of which 27 were from sporadic cases involving humans and 40 from outbreaks in humans; 14 isolates were from food, all but one connected with the outbreaks. All the isolates studied were sensitive to the antibiotics tested; plasmid profile analysis showed a predominant profile pattern in both epidemic and non-epidemic strains; lysine decarboxylase was present in all the strains tested. Although in at least three epidemics a common supplier of eggs was proved, the source was not identified. Unfortunately it was not possible to determine the phage type of isolates because of the unavailability of specific phages. PMID- 1854604 TI - Enzyme-linked immunoassays for the detection of Salmonella spp.: a comparison with other methods. AB - The first enzyme immunoassay for Salmonella was reported in 1977 and since that time several enzyme-linked immuno assays (ELISAs) have been developed, using either polyclonal or monoclonal antibodies that will detect most Salmonella serotypes. Two of these kits have been declared official first status by the Association of Official Analytical Chemists (AOAC). In comparison with a culture method used in collaborative studies, the total assay time is reduced by 2 days and statistical analysis of the data indicated no significant difference. The main problem related to all methods other than traditional culture methods is the occurrence of false-positive and/or false-negative results. False-positive ELISA results can be eliminated by using (combinations of) highly specific monoclonal antibodies. Good enrichment procedures are very important to be sure that the detection limit of approx. 10(5) cells/ml will be reached. In the future even better limits of detection may be achieved by using enzyme amplification or chemiluminescence to decrease the number of false-negative results. PMID- 1854605 TI - Slaughter pigs and pork as a source of human pathogenic Yersinia enterocolitica. AB - Pathogenic Yersinia enterocolitica strains (serogroups 0:3;0:9 and 0:5.27) were isolated from 36 (42%) of 86 porcine tonsils, 8 (20%) of 40 tongues, 17 (17%) of 100 rectal swabs and from 4 (1%) of 400 pork samples. Pathogenic Yersinia strains were not isolated from samples of 210 pig carcasses and from 20 samples of porcine head meat. These results confirm that pigs are an important reservoir of pathogenic Y. enterocolitica. However, contamination of carcasses during the slaughtering process with Yersinia from either faecal material or from the tonsillary region does not seem to occur frequently and this may also explain the low contamination rate of pathogenic Y. enterocolitica found for pork. For the isolation of pathogenic Y. enterocolitica strains from foods, enrichment in irgasan-ticarcillin-chlorate broth (ITC) and isolation on SS-deoxycholate-calcium agar (SSDC) is recommended. PMID- 1854606 TI - The late effects of cancer therapy in childhood. PMID- 1854607 TI - ras gene alterations in invasive and non-invasive rat bladder carcinomas induced by N-methyl-N-nitrosourea. AB - We have established a reliable method to induce invasive and non-invasive carcinomas in the heterotopically transplanted urinary bladder of rats by repeated injection of N-methyl-N-nitrosourea (MNU), and examined the alterations of the ras oncogenes and ras oncogene product (p21) in the induced tumours. The incidence of muscle-invasive carcinomas was proportional to the total dose of MNU. When 5, 6 or 12 doses of MNU were used, muscle invasive carcinomas developed in 22, 58 or 45% of animals, respectively, after a mean observation period, respectively, of 54 +/- 9, 45 +/- 13 and 38 +/- 3 weeks. Whereas activated H-ras gene was detected in only one non-invasive carcinoma by DNA transfection assay, seven of 18 non-invasive and invasive carcinomas showed activated ras p21 when examined by immunoblot analysis. Amplification or rearrangement of myc or epidermal growth factor (EGF) receptor gene was not observed. The results indicate that alterations of ras gene may be involved in the development of rat bladder carcinomas but not of invasiveness. PMID- 1854608 TI - The vascularity of cutaneous melanoma: a quantitative histological study of lesions 0.85-1.25 mm in thickness. AB - The vascularity of 107 primary cutaneous melanomas has been characterized by morphometric histological analysis. The lesions selected for study were of thickness 0.85-1.25 mm and the aim was to evaluate the prognostic significance of tumour vascularity. Two groups of patients were identified; 86 with no evidence of recurrence after a minimum follow-up period of 5 years and 21 with locoregional recurrence and/or metastasis. The lectin Ulex europaeus type I was used for endothelial cell staining of tissue sections and morphometric analysis was performed to derive the vascular length, surface and volume density from independent measurements of tumour, adjacent dermis and the junctional zone between tumour and underlying tissue. A wide range of values was obtained for each parameter with increased vascularity always found at the tumour base compared with the tumour as a whole. In relation to the adjacent normal dermis, vascularity was generally found to be higher at the tumour base but either higher or lower in the tumour overall. Tumour recurrence could not be predicted by any of the derived vascular parameters either independently or together with other histological and clinical features. This study suggests that tumour vascularity is of no prognostic significance in melanoma of the above thickness range. The highly variable extent of tumour vascularity was not correlated with other clinical or histological parameters, but may have implications for the delivery of pharmaceutical agents used for diagnosis or therapy. PMID- 1854609 TI - Comparative pathology of breast cancer in a randomised trial of screening. AB - In the Edinburgh Randomised Breast Screening Project (EBSP) to December 1988 there were 500 cancers in the study population invited to screening and 340 cancers identified in the control population. The size and negative lymph node status characteristics of invasive cancers from the two populations were significantly different (P less than 0.05). The cancers detected by screening were predominantly 'early stage', with 16% noninvasive (PTIS) and 42% invasive stage I (pT1 node negative), whereas cancers were frequently 'late stage' (more than pT2) and inoperable in nonattenders (44%) and controls (36%). Grouped according to customary size ranges of invasive cancers, the proportion of cases lymph node positive differed in those screen detected compared with controls, but the benefit in favour of screen detection was not constant. In comparisons of cancers detected at prevalence and incidence screens, as a test of conformity with screening theory, no significant differences were apparent according to size and lymph node status, yet the characteristics of histological type of cancer discriminated significantly (P less than 0.05). When these same histological characteristics were used to compare survival, the capacity to separate invasive cancers into two groups having good and poor survival probabilities was evident, with a significant improvement for the screen detected poor survival group compared with controls (P less than 0.05). PMID- 1854610 TI - Angiotensin II as a potential method of targeting cytotoxic-loaded microspheres in patients with colorectal liver metastases. AB - Regional chemotherapy is commonly used to treat patients with colorectal liver metastases. However, improvement in survival has still not been demonstrated. Cytotoxic loaded albumin microspheres for arterial administration have been described as a means of improving the the therapeutic index, but their distribution depends upon the prevailing pattern of arterial blood-flow at the time of injection. In this study, the ability of the vasoactive drug angiotensin II to target arterially injected microspheres to colorectal liver metastases is assessed in nine patients using scintigraphic planar and tomographic imaging. The median tumour: normal ratio in nine patients with colorectal liver metastases was 3.4:1 before the administration of angiotensin II. The corresponding ratio after administration of angiotensin II was 7.3:1. The median improvement factor was 1.8 (P less than 0.05). The data suggest that worthwhile tumour targeting can be achieved with angiotensin II in patients with colorectal liver metastases. PMID- 1854611 TI - The prognostic value of immunoperoxidase staining with monoclonal antibodies NCRC 11 and 3E1.2 in breast cancer. AB - The variation in survival of women with clinically similar breast cancers may lead to difficulty in clinical management so it is important to recognise factors which indicate the prognosis. Immunoperoxidase staining patterns of primary breast tumours using monoclonal antibody NCRC-11 have been shown to relate to overall survival (Ellis et al., 1985) but the results have not been reproducible in other centres. In this study paraffin sections of 483 primary breast cancers were stained with NCRC-11 and 3E1.2 using an immunoperoxidase system. The tumour staining patterns were compared with overall survival using life tables and tested for relative prognostic significance by Cox's multivariate analysis. NCRC 11 related to survival in all 483 cases (chi 2 5.8, P = 0.02) but both antibodies achieved maximum prognostic significance in lymph node negative patients (chi 2 9.4, P less than 0.002 and chi 2 10.7, P less than 0.001) in whom no other factor was more significant. Immunoperoxidase staining patterns produced by monoclonal antibodies NCRC-11 and 3E1.2 are important prognostic factors in breast cancer. PMID- 1854612 TI - Defective erythropoiesis in primary myelofibrosis associated with a chromosome 11 abnormality. AB - A case of primary myelofibrosis was identified with a previously unreported complex karyotype with two abnormal clones in addition to a proportion of normal cells: 46,XY,-2,-11, + der(2)t(2;11) (q24/31;q13), + mar and 45,XY,-2,-11, + der(2)t(2;11)(q24/31;q13), + mar, -17, del(7q). Study of circulating committed progenitors from this patient consistently showed (1) an absence of erythroid progenitors which is uncommon and (2) greatly increased granulocyte-monocyte progenitors (CFU-GM) which is generally observed in myelofibrosis. Further study showed that peripheral blood mononuclear cells co-cultured with irradiated normal bone marrow stroma generated increased numbers of CFU-GM compared with controls but failed to generate erythroid progenitors, providing evidence for an intrinsic defect in erythropoiesis. Only once previously has the absence of erythroid progenitors in primary myelofibrosis been studied in relation to cytogenetic abnormalities. This case also revealed a complex karyotype which, however, shared with our case a defect on chromosome 11. The identification of two cases of primary myelofibrosis which lack committed erythroid progenitor cells and which show in common a chromosomal defect on chromosome 11 point to the existence of genes on this chromosome which play a key role during erythropoiesis. PMID- 1854613 TI - DNA ploidy of primary breast cancer and local recurrence after breast-conserving therapy. AB - The value of DNA-flow cytometry and clinico-pathological prognostic factors for the prediction of local recurrences after breast-conserving therapy (BCT) were evaluated in a retrospective study. Thirty-one patients with a local recurrence were compared with 31 matched patients without a local recurrence. Morphology and DNA-indices of the local recurrences and their corresponding primary tumours were compared. Ductal carcinoma in situ was present significantly more often in the group with a primary recurring tumour, than in the matched group (P less than 0.001), and the same holds for lobular carcinoma (n = 5). Half of the tumours that recurred had macroscopically positive surgical margins compared to about one fourth of the matched group. Fifty-six per cent of the DNA-aneuploid stemlines in cases with local recurrence were present in the corresponding primary tumour as well (confidence limits 45%-75%), an indication that the majority of local recurrences are true recurrences and not independently developed tumours. The lack of similarity of DNA stemlines between some primary DNA-aneuploid tumours and their local recurrences indicates that these tumours had developed independently. The percentage of DNA-aneuploid cases in the group with local recurrence (89%) did not differ significantly from that in the matched group (70%). However, the findings suggest a selective recurrence of DNA-diploid stemlines. This might indicate increased resistance of DNA-diploid tumour cells to radiotherapy as compared with the resistance level in DNA-aneuploid cells. PMID- 1854614 TI - Seasonal changes in serum melatonin in women with previous breast cancer. AB - A seasonal variation in the month of initial detection of breast cancer has been previously observed in pre-menopausal women, and it has been proposed that this may be due to cyclic changes in tumour growth mediated by the effects of melatonin on ovarian function. To investigate this possibility serum melatonin concentrations have been measured every 2 h for 24 h at the summer and winter solstice in 20 pre-menopausal women with previous breast cancer and nine controls. Twelve women had detected their tumour in winter and eight in summer. Overall melatonin secretion assessed by either amplitude of the nocturnal melatonin pulse or the area under the 24 h melatonin curve (AUC) was not different between breast cancer women or controls. However, the amplitude and AUC fell in winter in breast cancer patients (summer to winter 93.6 to 77.5 pg ml-1, P less than 0.002 and 743 to 634 AUC units, P less than 0.005 for amplitude and AUC respectively), whereas the winter minus summer values were significantly positive in controls compared with cancer patients. The abnormal fall in winter values in the women with previous breast cancer was confined to the group of women who had been winter detectors (mean summer to winter levels 94.9 to 72.6 pg ml-1, P less than 0.01 and 775 to 637 AUC units, P less than 0.05 for amplitude and AUC respectively) whereas there was no significant seasonal alteration in these measurements in summer detectors. The acrophase of the nocturnal pulse of serum melatonin was significantly advanced in both groups of women with previous breast cancer (change in acrophase winter to summer from 0210 h to 0140 h in summer detectors, P less than 0.01, 0330 h to 0210 h in winter detectors, P less than 0.05) with a similar although nonsignificant trend in control women. The abnormal reduction of serum melatonin seen in wintertime in winter detectors of breast cancer could promote tumour growth at this season and so contribute to the decreased survival previously observed in this group compared with summer detectors. The relatively normal seasonal profile of melatonin observed in summer detectors could allow increased ovarian steroidogenesis in spring/summer with a resulting increase in tumour growth and consequent rise in tumour detection rate at this time. PMID- 1854615 TI - Evaluation of serum CA15-3 determination with CEA and TPA in the post-operative follow-up of breast cancer patients. AB - The usefulness of post-operatively serial serum CA15-3 determination with CEA and TPA was evaluated in a group of 285 breast cancer patients. In particular, the CA15-3 sensitivity to 'early' diagnosis and monitoring of the response to treatment of breast cancer relapses, was compared with those of the two other markers in order to define the most suitable association. Moreover, in a group of 169 non relapsed patients with a prolonged follow-up (40 +/- 8 months; mean +/- s.d.) CA15-3 specificity was investigated. During post-operative follow-up in 27 (10%) patients, distant metastases occurred. In most of them, elevated values of one or more tumour markers were the first pathological sign and CA15-3, CEA and TPA sensitivity to 'early' diagnosis of metastases were 46%, 7% and 63% respectively. When each tumour marker was considered in combination, CA15-3-CEA TPA association showed a higher sensitivity (87%) than both CA15-3-TPA (83%) and the CEA-TPA (70%). Serum CA15-3 increase preceded the certain sign of metastases 2.7 +/- 2.6 months (mean +/- s.d.). Shortly before appearance and during treatment of distant metastases, constant elevation and/or progressive increase in serum CA15-3 values occurred in all evaluated patients except three in whom isolated elevated values were found as well. In 24 (14%) of 169 non relapsed patients with prolonged follow-up (40 +/- 8 months; mean +/- s.d.) high serum CA15-3 values occurred. In 16 of these 24 patients, an isolated elevated value was found, while four (2.3%) or the eight remaining ones with constant elevation and/or progressive increase were falsely suspected of metastases. In this group of non relapsed patients, chronic liver failure, diabetes and/or hepatic steatosis were the reasons more commonly responsible for the CA15-3 increase. In metastatic patients, no organ-specificity was shown either by CA15-3 or by CEA and TPA. In these patients serum TPA values showed the highest sensitivity and paralleled clinical and/or instrumental signs better than the CA15-3 and even more than CEA values. These data indicate that in the post-operative follow-up of breast cancer patients, TPA is the most useful tumour marker and TPA-CA15-3 the most suitable association. Contemporaneous measurement of serum CEA levels only slightly increases sensitivity and positive predictive value of TPA-CA15-3 combination. PMID- 1854616 TI - Cancer risks in thyroid cancer patients. AB - Cancer risks were studied in 834 thyroid cancer patients given 131I (4,551 MBq, average) and in 1,121 patients treated by other means in Sweden between 1950 and 1975. Record-linkage with the Swedish Cancer Register identified 99 new cancers more than 2 years after 131I therapy [standardised incidence ratio (SIR) = 1.43; 95% confidence interval (CI) 1.17-1.75] vs 122 (SIR = 1.19; 95% CI 0.88-1.42) in patients not receiving 131I. In females treated with 131I overall SIR was 1.45 (95% CI 1.14-1.83) and significantly elevated were noted for tumours of the salivary glands, genital organs, kidney and adrenal gland. No elevated risk of a subsequent breast cancer or leukaemia was noted. SIR did not change over time, arguing against a strong radiation effect of 131I. Organs that were estimated to have received more than 1.0 Gy had together a significantly increased risk of a subsequent cancer following 131I treatment (SIR = 2.59; n = 18). A significant trend was seen for increasing activities of 131I with highest risk for patients exposed to greater than or equal to 3,664 MBq (SIR = 1.80; 95% CI 1.20-2.58). No specific cancer or group of cancers could be convincingly linked to high-dose 131I exposures since SIR did not increase after 10 years of observation. However, upper confidence intervals could not exclude levels of risk that would be predicted based on data from the study of atomic bomb survivors. We conclude that the current practice of extrapolating the effects of high-dose exposures to lower dose situations is unlikely to seriously underestimate radiation hazards for low LET radiation. PMID- 1854617 TI - The influence of serum methotrexate concentrations and drug dosage on outcome in childhood acute lymphoblastic leukaemia. AB - Sequential methotrexate (Mtx) absorption studies were undertaken in 127 children undergoing treatment for childhood non-T acute lymphoblastic leukaemia (ALL) to determine whether serum drug concentration, clearance and dosage affect event free survival (EFS). Higher serum concentration and area under the plasma concentration curve (AUC) were not associated with an improved EFS. Methotrexate clearance was not found to be of prognostic significance. Patients who tolerated only low 6-mercaptopurine (6-MP) doses because of neutropaenia and those who randomly were prescribed higher doses of Mtx had a lower rate of leukaemia relapse after the completion of therapy. This suggests that the use of maintenance therapy in maximally tolerated doses may be associated with an increased survival in childhood ALL. PMID- 1854618 TI - c-Ki-ras gene mutations in dysplasia and carcinomas complicating ulcerative colitis. AB - One hundred and nine samples comprising carcinomas, adenomas, dysplastic, inflamed and normal mucosa from patients with sporadic colon cancer and ulcerative colitis (UC) were analysed for c-Ki-ras mutations. DNA was extracted from archival paraffin-embedded material, amplified using the polymerase chain reaction (PCR) and the PCR products analysed using restriction enzyme digestion. Forty-two per cent (14/33) of the sporadic carcinoma controls contained Ki-ras codon 12 mutations in contrast to 24% (8/33) of ulcerative colitis carcinomas. A significantly higher c-Ki-ras mutation rate was observed in rectal carcinomas (72%) in comparison to colonic carcinomas (28%) in control patients (P less than 0.04), while the opposite was observed in UC patients. The difference between the incidence of c-Ki-ras mutations in rectal carcinomas in UC (9%) and in sporadic rectal carcinomas (72%) was also significant (P less than 0.01). This lower prevalence rate and different site distribution of c-Ki-ras mutations in UC carcinomas compared to sporadic carcinomas suggests that specific genetic differences may underlie the causation of carcinomas arising in these situations. PMID- 1854619 TI - Cathepsin D assay in ovarian cancer: correlation with pathological features and receptors for oestrogen, progesterone and epidermal growth factor. AB - Using an immunoradiometric assay, Cathepsin-D (Cath-D) concentrations were measured in the cytosol of 68 normal and neoplastic human ovarian tissues. Cath-D levels were higher in malignant tumours than in normal tissue samples (P less than 0.01) and benign tumours (P less than 0.01). In six out of seven cases, metastatic deposits showed Cath-D concentrations higher than the respective primary tumours. Using 12 of 17 pmols.mg-1 protein as cut-off levels, the Cath-D status (high or low) was not related to any pathological parameter. Moreover, no correlation was found between Cath-D levels and receptors for oestrogen, progesterone and epidermal growth factor. Our results indicate that ovarian tumours produce Cath-D. Further studies are needed to evaluate whether this protein could represent a prognostic factor for this neoplasia. PMID- 1854620 TI - Cancer patterns among Vietnamese immigrants in Los Angeles County. PMID- 1854621 TI - The role of diet in the development of breast cancer: a case-control study of patients with breast cancer, benign epithelial hyperplasia and fibrocystic disease of the breast. AB - A case-control study was undertaken to investigate the role of diet in women with breast cancer, and in two groups of women with benign breast disease: epithelial hyperplasia, and fibrocystic disease without hyperplasia. The study provides data which suggest that the consumption of red meat, savoury meals (pizza, pies, stew, etc.) and of starches is disadvantageous, while the consumption of chicken and fish, and of fruit, appears to be beneficial. These patterns were present for both the breast cancer patients and the patients with benign epithelial hyperplasia. One-third of breast cancer patients had changed their diet after their diagnosis, compared to only around 12% in controls and patients with benign breast disease. Overall, the women studied had changed their diet to reduce their intake of sugars, dairy products and meat, and increased their intake of poultry, fish, fruit and vegetables over the past decade; but the breast cancer group was less likely to have made this change. PMID- 1854622 TI - Drug-target interactions: only the first step in the commitment to a programmed cell death? AB - The search for novel antitumour drugs has reached a plateau phase. The carcinomas remain almost as intractable as they did 40 years ago and the need for effective therapy is pressing. There is an argument that the current pharmacopoeia is sufficient but, to be effective, the biochemical mechanisms of drug resistance must be circumvented. In tackling the question of why certain cancer cells are resistant, the converse question of why others are sensitive still remains to be answered fully. Asking the fundamental question of why and how a cell dies may provide clues as to what avenues lie open for improved chemotherapy. In this review we survey the recent literature on cell death and we argue that it is possible that the outcome of chemotherapy may be determined by the response of the cell to the formation of the drug-target complex, and/or its sequellae, rather than to the biochemical changes brought about by the drug alone. One of these responses, determined by the phenotype of the cell, may be activation of a genetic programme for cell death. PMID- 1854623 TI - 25th Paterson Symposium--is there a future for radiosensitivity testing? PMID- 1854624 TI - Lung cancer and passive smoking (continued) PMID- 1854625 TI - Kaposi's sarcoma. PMID- 1854626 TI - Comparison of the antitumour effects and nephrotoxicity-inducing activities of two new platinum complexes, (-)-(R)-2-aminomethylpyrrolidine(1,1 cyclobutanedicarboxylato+ ++)-platinum (II) monohydrate, and its enantiomeric isomer. AB - New platinum complexes, (-)-(R)-2-aminomethylpyrrolidine(1,1- cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114R) and its enantiomeric isomer, (+)-(S)-2-aminomethylpyrrolidine(1,1- cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114S), were compared in their antitumour effects and nephrotoxicity-inducing activities. Both compounds were effective against the murine tumours L1210 and Colon 26 by i.p. injection of 20-100 mg kg-1. While DWA2114S showed marked increases in blood urea nitrogen (BUN) and urinary protein and sugar in BDF1 mice treated i.p. at the maximum tolerated dose, DWA2114R showed no increases in these parameters. To clarify the difference of nephrotoxicity between the isomers, tissue distribution was examined. Renal Pt concentration in DWA2114S-treated mice was more than 5-fold higher compared with that in DWA2114R-treated mice 2h after i.p. injection of 80 mg kg-1. However, there were no such marked differences in the lung, liver, heart, spleen and plasma. The low content of Pt in the kidneys of DWA2114R treated mice could explain its lower nephrotoxicity. The in vitro experiments for uptake of the drugs into the cultured normal rat kidney cells and fresh splenocytes revealed that the Pt amount in the cells treated with DWA2114S, especially in the kidney cells, was much higher than DWA2114R. PMID- 1854627 TI - Changes in tumour morphology with alterations in oxygen availability: further evidence for oxygen as a limiting substrate. AB - The ability of cancer cells to survive at a distance from blood vessels should be dependent on the local supply of nutrients to each vessel. The corded growth of tumour cells around blood vessels within regions of necrosis in the RH carcinoma in the mouse allows the limit to which cells can be supported by individual vessels to be observed. The thickness of individual tumour cords was measured in conventionally stained tumour sections using a scanning technique to determine the distance between the blood vessel wall and the most distant viable cell adjacent to necrosis. Cord radius was found to vary with the oxygen supply conditions. Control animals had a mean radius of 105 +/- 2 microns while animals that had breathed 10% oxygen had significantly narrower cords (93 +/- 3 microns after 48 h) and animals breathing 100% oxygen had significantly wider cords (117 +/- 3 microns after 24 h). Mice made anaemic (mean hct. 28%) by phlebotomy and plasma transfusion had cord radii that were not significantly different from controls at any time up to 48 h. We conclude that this relatively slow growing mouse tumour is capable of rapid morphological adaptation (less than 3 h) to changes in nutrient availability and that oxygen is probably the limiting substrate. PMID- 1854628 TI - The detection of alkylation damage in the DNA of human gastrointestinal tissues. AB - Damage arising from putative environmental sources has been found in the DNA of the gastric and colorectal mucosae of patients presenting with gastrointestinal disorders from the South Manchester area. O6-Methylguanine (O6-MeG) in the range 0.010- greater than 0.300 mu moles mole-1 adenine was heterogeneously distributed both between and within individuals. The pattern of alkylation of tissue DNA appears to differ when comparison is made between gastric and colorectal samples. Most of the gastric tumour DNA samples were alkylated (5/6; 0.087 +/- 0.097), whereas the DNA of the associated mucosa was alkylated less frequently (2/7) and to a lesser extent; (0.017 +/- 0.030; P = 0.07). Conversely, colorectal tumour DNA was alkylated infrequently (1/7) and to a lower extent (0.003 +/- 0.007) than the DNA of the adjacent mucosa (8/10 samples alkylated with a mean of 0.083 +/- 0.106; P = less than 0.01), or indeed of any other tissue. Although increased levels of DNA damage in tissue associated with malignant disease have been indicated by independent studies of DNA damage at other cancer sites, significant differences were not observed in the present report, neither was there any suggestion of a relationship with smoking or alcohol consumption. The data provided by this report indicate that exposure to putative environmental alkylating agents occurs in the UK at levels comparable to those previously detected in areas of higher cancer risk. Although we cannot determine the extent to which this DNA damage is attributable to normal background exposures, it is evident that the alkylation of tissue DNA occurs and is not uniform. In conjunction with other reports, therefore these differences may begin to provide indications of mechanisms that could be of relevance in the aetiology of gastrointestinal cancers. PMID- 1854629 TI - The identification of heme oxygenase as a major hypoxic stress protein in Chinese hamster ovary cells. AB - Chronic hypoxia increases the expression of a set of stress proteins (oxygen regulated proteins or ORPs) which is implicated in the development of drug resistance and radiation sensitivity in tumour cells. Five major ORPs have been documented, and two, ORP 80 and ORP 100, are considered to be identical to the glucose regulated stress proteins GRP78 and GRP94, respectively. We report here that ORP 33 is a form of the heme catabolic enzyme, heme oxygenase, using evidence obtained from northern blotting, two-dimensional polyacrylamide gel electrophoresis and western analysis. Heme oxygenase is believed to be an important component of the cellular response to oxidative stress. The significance of heme oxygenase as a hypoxia-induced stress protein is discussed. PMID- 1854630 TI - Chemotherapy for metastatic soft tissue sarcomas--another full circle? PMID- 1854631 TI - Antitumour response and nephrotoxicity following intraperitoneal administration of a slow release formulation of cisplatin to rats bearing cancers restricted to the peritoneal cavity. PMID- 1854632 TI - Tumour-localising and -photosensitizing properties of liposome-delivered Ge(IV) octabutoxy-phthalocyanine. PMID- 1854633 TI - The long term prognostic significance of oestrogen receptor analysis in early carcinoma of the breast. AB - The long term prognostic significance of oestrogen receptors was assessed in a prospective study of 767 patients presenting between the years 1975 and 1981 with stage 1 and 2 breast cancer treated by mastectomy with either full axillary dissection or nodal sampling. Oestrogen receptor binding was determined by a dextran coated charcoal method and median follow up was 11 years. Oestrogen receptors were present in 396 (54%) of tumours. Absence of oestrogen receptors was associated with tumours of high histological grade, but there was no relationship between nodal status or tumour size. Oestrogen receptor status did not predict survival for the group as a whole or when stratified by nodal status. In multivariate analysis both nodal status and tumour size were powerful independent prognostic factors, but oestrogen receptors failed to achieve statistical significance. PMID- 1854634 TI - Taxonomy and pathogenicity of Erwinia cacticida sp. nov. AB - A total of 108 pectolytic, soft-rotting Erwinia strains were collected from 11 types of cacti growing in Arizona, Texas, northern Mexico, and Australia between 1958 and 1989. Four strains were collected from soils beneath or close to naturally rotting saguaro cacti. Collectively, these strains caused soft rots of saguaro, organ pipe, and senita cacti, Opuntia (cactus) fruits and pads, tomato fruits, and potato slices, but only occasionally caused soft rots of slices of carrot roots. A numerical cluster analysis showed that 98 of the 112 strains formed a uniform group (cluster 1A) that was distinguished from other pectolytic erwinias by an API 20E code of 1205131, by negative reactions in API 50CHE tests for L-arabinose, myo-inositol, D-cellobiose, melibiose, and D-raffinose, and, in supplemental tests, by positive reactions for malonate and growth at 43 degrees C. The average levels of DNA relatedness of 22 cluster 1A strains to the proposed type strain (strain 1-12) as determined by the hydroxyapatite method were 88% in 60 degrees C reactions (with 1% divergence within related sequences) and 87% in 75 degrees C reactions. The levels of relatedness to the type strains of other Erwinia spp. were less than or equal to 38% in 75 degrees C reactions. Cluster 1A strains also had a characteristic cellular fatty acid profile containing cyclo (11,12)-nonadecanoic acid (C19:0 Cyclo C11-12) and missing tridecanoic acid (C13:0), heptadecanoic acid (C17:0), and cis-9-heptadecenoic acid (C17:1 CIS 9), which separated them from other pectolytic erwinias. Collectively, these data indicate that the members of cluster 1A are members of a new species, which we name Erwinia cacticida. Three cactus strains in cluster 1B appear to represent a second new species that is closely related to E. cacticida; these strains are designated E. cacticida-like pending the availability of additional strains for testing. The remaining cactus strains (in cluster 4) have the physiological, DNA, and fatty acid profiles of Erwinia carotovora. PMID- 1854635 TI - Distribution and phylogenetic significance of 27-hydroxy-octacosanoic acid in lipopolysaccharides from bacteria belonging to the alpha-2 subgroup of Proteobacteria. AB - Lipopolysaccharides (LPSs) from a number of bacteria belonging to the alpha-2 subgroup of the class Proteobacteria were screened for the presence of 27-hydroxy octacosanoic acid (27-OH-28:0). With few exceptions, most of the bacteria contained 27-OH-28:0 in their lipid A fractions. In addition, some of the bacteria contained other n-2-hydroxylated long-chain fatty acids hitherto not reported. The distribution of 27-OH-28:0 was restricted to the alpha-2 subgroup. LPSs from members of the other subgroups (the beta and gamma subgroups), including some well-characterized enterobacterial LPSs, were devoid of 27-OH 28:0. Our results indicate that the presence of n-2-hydroxylated long-chain fatty acids in LPSs might be used as a chemophylogenetical marker. PMID- 1854637 TI - Mycoplasma spermatophilum, a new species isolated from human spermatozoa and cervix. AB - A mycoplasma isolated from human spermatozoa and a human cervix was shown to be serologically distinct from 98 previously recognized Mycoplasma and Acholeplasma spp. Six mycoplasma colonies were cloned and examined in detail for morphology, growth, and biochemical characteristics; five of these were from sperm samples and one was from a cervix. These strains were closely related and had the following properties: guanine-plus-cytosine content of 32 mol%, requirement for sterol, and anaerobic growth. Glucose was not metabolized, and arginine and urea were not hydrolyzed. Strain AH159 (= NCTC 11720) is the type strain of a new species, Mycoplasma spermatophilum. PMID- 1854636 TI - Wolinella recta, Wolinella curva, Bacteroides ureolyticus, and Bacteroides gracilis are microaerophiles, not anaerobes. AB - Although the nonfermentative, asaccharolytic, putative anaerobes Wolinella curva, Wolinella recta, Bacteroides ureolyticus, and Bacteroides gracilis are phylogenetically related to the true campylobacters, the type strains of these species exhibited O2-dependent microaerophilic growth in brucella broth and on brucella agar. The optimum O2 levels for growth of these strains ranged from 4 to 14% in brucella broth and from 2 to 8% on brucella agar, when H2 was provided as the electron donor. No growth occurred under 21% O2, and scant or no growth occurred under anaerobic conditions unless fumarate or nitrate was provided as a terminal electron acceptor. Aspartate, asparagine, and malate also served as apparent electron acceptors. The organisms were catalase negative and, except for B. gracilis, oxidase positive. Catalase added to brucella broth enhanced growth. O2 uptake by all species was inhibited by cyanide and 2-heptyl-4-hydroxyquinoline N-oxide. We concluded that these organisms are not anaerobes but instead are microaerophiles, like their campylobacter relatives. PMID- 1854638 TI - Polyacrylamide gel electrophoresis analysis of ribosomal protein AT-L30 as a novel approach to actinomycete taxonomy: application to the genera Actinomadura and Microtetraspora. AB - Actinomycete ribosomal protein AT-L30 exhibits electrophoretic mobility that is specific for each genus. On the basis of this fact, we analyzed ribosomal AT-L30 proteins from 26 type strains of species belonging to the genera Actinomadura and Microtetraspora. The electrophoretic mobilities of AT-L30 preparations from these strains, as determined by two-dimensional polyacrylamide gel electrophoresis, revealed that they could be divided into two groups, one group with relative electrophoretic mobilities of 14.0 to 41.5 and another group with relative electrophoretic mobilities of -6.5 to 0. The first group corresponded to the genus Actinomadura, and the second group corresponded to the genus Microtetraspora. Partial amino acid sequencing of AT-L30 preparations from several strains proved that we were indeed dealing with the specified protein homologous to ribosomal protein L30 of Escherichia coli. Our results strongly supported the conclusions of previous work and thus proved the efficacy of ribosomal protein analysis as a novel approach for taxonomy of actinomycetes. PMID- 1854639 TI - Characterization of yeast strains of the genera candida, Hansenula, Kluyveromyces, Pichia, Rhodotorula, and Saccharomyces by mixed-dye fluorometry. AB - An analytical method in which we used the selective adsorption of several fluorophores by yeast cells is described. The suitability of using binary mixtures of 1-pyrene butyric acid, 3,6-dimethylamino acridine, 4-acetamido-4' isothiocyanatostilbene-2,2'-disulfonic acid, and rhodamine B isothiocyanate for the characterization and identification of microorganisms was tested with 98 yeast strains belonging to the genera Candida, Hansenula, Kluyveromyces, Pichia, Rhodotorula, and Saccharomyces. The application of multivariate statistical methods and pattern recognition methods to the allocation of the yeast strains into genus-species-strain structures and to a comparison of fluorescence data sets for differentiation and identification purposes showed the usefulness of the method. PMID- 1854640 TI - Lactobacillus uli sp. nov. and Lactobacillus rimae sp. nov. from the human gingival crevice and emended descriptions of lactobacillus minutus and Streptococcus parvulus. AB - Lactobacillus uli sp. nov. and Lactobacillus rimae sp. nov. are described. These organisms are short, gram-positive, strictly anaerobic, rod-shaped bacteria that have DNA G+C contents of 53 and 45 mol%, respectively, produce major amounts of lactic acid, and have been isolated from human gingival crevices and periodontal pockets. The major cellular fatty acid derivatives for both species are C18:1 cis 9 fatty acid methyl ester and C18:1 cis-9 dimethylacetyl. The type strain of L. uli is strain VPI D76D-27C (= ATCC 49627), and the type strain of L. rimae is strain D140H-11A (= ATCC 49626). Emended descriptions of Lactobacillus minutus (based on selected strains) and Streptococcus parvulus (based on many additional strains) also are given. PMID- 1854641 TI - Staphylococcus cohnii subspecies: Staphylococcus cohnii subsp. cohnii subsp. nov. and Staphylococcus cohnii subsp. urealyticum subsp. nov. AB - Two major subspecies of Staphylococcus cohnii, namely S. cohnii subsp. cohnii, from humans, and S. cohnii subsp. urealyticum, from humans and other primates, are described on the basis of a study of 14 to 25 strains and 18 to 33 strains, respectively. DNA-DNA hybridization studies conducted in our laboratory in 1983 (W. E. Kloos and J. F. Wolfshohl, Curr. Microbiol. 8:115-121, 1983) demonstrated that strains representing the different subspecies were significantly divergent. S. cohnii subsp. urealyticum can be distinguished from S. cohnii subsp. cohnii on the basis of its greater colony size; pigmentation; positive urease, beta glucuronidase, and beta-galactosidase activities; delayed alkaline phosphatase activity; ability to produce acid aerobically from alpha-lactose; and fatty acid profile. The type strain of S. cohnii subsp. cohnii is ATCC 29974, the designated type strain of S. cohnii Schleifer and Kloos 1975b, 55. The type strain of S. cohnii subsp. urealyticum is ATCC 49330. PMID- 1854642 TI - Vibrio navarrensis sp. nov., a species from sewage. AB - A group of 11 strains, mostly isolated from sewage water in the Province of Navarra, Spain, were found to constitute a DNA relatedness group which is 2 to 39% related to 23 species of the genus Vibrio and 2 to 3% related to two Aeromonas species. Phenotypically, these strains have all of the properties that define the genus Vibrio. However, they differ from the previously described species by three or more properties. The strains are negative for arginine, ornithine, and lysine decarboxylase activities and the Voges-Proskauer test and are unable to utilize putrescine, gluconate, glucuronate, and histidine. They utilize and produce acid from sucrose and grow at 40 degrees C. All strains grow in the presence of 0.5% (wt/vol) NaCl, and seven strains grow weakly in peptone water lacking NaCl. The group of strains which we studied can also be differentiated from other Vibrio species by fatty acid content. The G+C ratio of the DNA is 45 to 47 mol%. The name Vibrio navarrensis sp. nov. is proposed for these strains; strain 1397-6 (= CIP 103381) is the type strain. PMID- 1854643 TI - Two cellulolytic Clostridium species: Clostridium cellulosi sp. nov. and Clostridium cellulofermentans sp. nov. AB - Two cellulolytic clostridia, one thermophilic and the other mesophilic, were isolated and characterized. Cells of the thermophile are gram-negative rods that are motile with lophotrichous flagella and spherical terminal endospores which swell the cells. The optimum growth temperature is 55 to 60 degrees C, with a range of 40 to 65 degrees C. The deoxyribonucleic acid composition is 35 mol% G + C. The name Clostridium cellulosi sp. nov. is proposed. The type strain is AS 1.1777. Cells of the mesophile are gram negative and motile with peritrichous flagella and terminal oval or spherical spores which swell the cells. The deoxyribonucleic acid composition is 34 mol% G + C. The name Clostridium cellulofermentans sp. nov. is proposed. The type strain is AS 1.1775. Both C. cellulosi AS 1.1777 and C. cellulofermentans AS 1.1775 are deposited in the China Committee for Culture Collection of Microorganisms, Institute of Microbiology, Academia Sinica, Beijing, People's Republic of China. PMID- 1854644 TI - Phylogenetic analysis of Aquaspirillum magnetotacticum using polymerase chain reaction-amplified 16S rRNA-specific DNA. AB - The 16S rRNA gene of the magnetotactic magnetogen Aquaspirillum magnetotacticum MS1 was amplified by a polymerase chain reaction, using two eubacterial consensus oligodeoxynucleotide primers flanking the majority of the 16S rRNA gene, cloned, and sequenced. Phylogenetic analysis revealed that A. magnetotacticum MS1 belongs to the alpha-group of proteobacteria. This assignment offers perspective on the biochemical properties of A. magnetotacticum, since this organism is expected to have the general properties that are common to this phylogenetic group. PMID- 1854645 TI - Health and the environment. PMID- 1854647 TI - Occupational medicine for one and all. AB - In the 1930s in Britain, industrial medicine was a clinical discipline, the main purposes of which were to diagnose disability in applicants for work, to identify industrial disease in the dangerous trades, and to provide first aid treatment for those injured or taken sick in the workplace. Following rapid developments in epidemiology and occupational hygiene and with more emphasis on "group health" and less on "individual care", occupational medicine has tended to become less of a clinical discipline; yet clinical skills are needed to assess fitness for work, to identify adverse effects of work, and to undertake consultations on a variety of health problems. Although care of the individual worker is a major task, an occupational health service has a responsibility for the health of the workforce as a whole, using epidemiology to plan and administer health care, to identify and control work related disorders, and to promote health by identifying positive factors in the organisation that induce a sense of well being; and by health screening and education programmes. Academic occupational health should not lose its identity as a clinical discipline in any merger with environmental health. Medical skills are needed to assess fitness for work and to identify human responses to adverse factors in the environment and to evaluate control measures. PMID- 1854646 TI - The toxicity of benzene and its metabolism and molecular pathology in human risk assessment. AB - Benzene, a common industrial chemical and a component of gasoline, is radiomimetic and exposure may lead progressively to aplastic anaemia, leukaemia, and multiple myeloma. Although benzene has been shown to cause many types of genetic damage, it has consistently been classified as a non-mutagen in the Ames test, possibly because of the inadequacy of the S9 microsomal activation system. The metabolism of benzene is complex, yielding glucuronide and sulphate conjugates of phenol, quinol, and catechol, L-phenylmercapturic acid, and muconaldehyde and trans, trans-muconic acid by ring scission. Quinol is oxidised to p-benzoquinone, which binds to vital cellular components or undergoes redox cycling to generate oxygen radicals; muconaldehyde, like p-benzoquinone, is toxic through depletion of intracellular glutathione. Exposure to benzene may also induce the microsomal mixed function oxidase, cytochrome P450 IIE1, which is probably responsible for the oxygenation of benzene, but also has a propensity to generate oxygen radicals. The radiomimetic nature of benzene and its ability to induce different sites of neoplasia indicate that formation of oxygen radicals is a major cause of benzene toxicity, which involves multiple mechanisms including synergism between arylating and glutathione-depleting reactive metabolites and oxygen radicals. The occupational exposure limit in the United Kingdom (MEL) and the United States (PEL) was 10 ppm based on the association of benzene exposure with aplastic anaemia, but recently was lowered to 5 ppm and 1 ppm respectively, reflecting a concern for the risk of neoplasia. The American Conference of Governmental Industrial Hygienists (ACGIH) has even more recently recommended that, as benzene is considered an A1 carcinogen, the threshold limit value (TLV) should be decreased to 0.1 ppm. Only one study in man, based on nine cases of benzene associated fatal neoplasia, has been considered suitable for risk assessment. Recent re-evaluation of these data indicated that past assessments may have overestimated the risk, and different authors have considered that lifetime exposure to benzene at 1 ppm would result in an excess of leukaemia deaths of 9.5 to 1.0 per 1000. Although in this study, deaths at low levels of benzene exposure were associated with multiple myeloma and a long latency period, instead of leukaemia, which might justify further lowering of the exposure limit, the risk assessment model has been found to be non-significant for response at low levels of exposure. The paucity of data for man, the complexity of the metabolic activation of benzene, the interactive and synergistic mechanisms of benzene toxicity and carcinogenicity, the different disease endpoints (aplastic anaemia, leukaemia, and multiple myeloma), and different individual susceptibilities, all indicate that in such a complex scenario, regulators should proceed with caution before making further changes to the exposure limit for this chemical. PMID- 1854648 TI - Environmental, occupational, and personal factors related to the prevalence of sick building syndrome in the general population. AB - Possible relations between prevalence of sick building syndrome (SBS) and environmental, occupational, and personal factors were studied in a random sample (0.1%) of the general population aged 20-65 in a three county region in middle Sweden. Childhood exposure to environmental tobacco smoke from smoking mothers and a childhood in urban areas was related to SBS symptoms. Current urban residency, fresh paint, and preschool children in the dwelling were also related to symptoms. Other residential factors such as age of building, type of building, degree of crowding, mechanical ventilation, or signs of moisture or mould growth were not related to symptoms. Other factors related to symptoms were history of atopy, allergy to nickel, proneness to infection, hyperreactivity, static electricity, work with video display units (VDU), work satisfaction, and climate of cooperation at work. Age, sex, marital state, education level, work stress, obesity, current or earlier smoking, regular physical exercise, or occupational exposure to chemicals did not correlate with symptoms. Women had a higher proportion of symptoms than men but these differences were not significant when adjusting for differences in allergy to nickel, hyperreactivity, and proneness to infection. Maternal smoking was related to a twofold increase of both atopy and allergy to nickel in the adult offspring. Eye symptoms were most common in administrative, managerial, and service work. Airway symptoms were most common in transport and communication work. Dermal symptoms were most common in professional and technical and related work. General symptoms were most common in service, health, hospital, and social work. The lowest prevalence of symptoms was found in agricultural, forestry, and sales work. Women and subjects allergic to nickel worked more often in occupations without exposure to chemicals, but no evidence was found for selection mechanisms causing sensitive persons to move from exposed to unexposed occupations. It was concluded that symptoms included in SBS are common in the general population, and of multifactorial origin related to both personal, occupational, and residential factors, and certain environmental exposures such as maternal smoking, the urban environment, VDU work, and volatile organic hydrocarbons from newly painted dwellings. PMID- 1854649 TI - Chest x ray screening for lung cancer at three British chromates plants from 1955 to 1989. AB - Chest x ray screening for lung cancer had been undertaken over a period of 34 years, initially at yearly intervals, then at eight-monthly intervals, on chromates workers at three plants in the United Kingdom. A review of the records of 229 employees who were diagnosed as having carcinoma of the lung during the screening programme was conducted. Survival data were available on 124 cases (123 now deceased) who constitute the study population. The cases were analysed by age and regularity of attendance for screening. The numbers detected by works x ray screening and by other means were determined with five and 10 year survival rates. A modest but predictable improvement in the five year survival of those who attended regularly for radiography was shown. Taking the total population of cases for whom screening was available, no significant improvement in five year survival was found. PMID- 1854650 TI - Finger blood pressure and rewarming rate for screening and diagnosis of Raynaud's phenomenon in workers exposed to vibration. AB - Both the finger systolic blood pressure (FSP) and the rewarming test of finger skin are measures of circulation in the finger; the first reflects the vasoconstriction phase and the second the vasodilatation phase. The combinations of the specificity and the sensitivity of these methods were evaluated by a receiver operating characteristic curve (ROC). The material included 37 vibration induced white finger (VWF) cases, five primary Raynaud's cases, and 37 controls. The specificity of the FSP test was high with regard to the anamnesis of white finger and the test was useful for the diagnosis of Raynaud's phenomenon, but the sensitivity was too low for screening. The rewarming test was useful for screening primary Raynaud's case and possibly for screening disorders in peripheral vasodilative function. The connections between the rewarming test and VWF are not clear and according to the present study the rewarming test was not suitable for screening VWF. PMID- 1854651 TI - Thioether excretion in urine of applicators exposed to 1,3-dichloropropene: a comparison with urinary mercapturic acid excretion. AB - The excretion of thioethers in urine of applicators occupationally exposed to the soil fumigant 1,3-dichloropropene (DCP) was determined by the thioether assay. The mercapturic acid metabolite of E-1,3-dichloropropene, N-acetyl-S-(E-3 chloropropenyl-2-)-L-cysteine (E-DCP-MA), was the reference compound in the thioether assay. The mean recovery of E-DCP-MA was 58.5% (coefficient of variation (CV) 9%, n = 4). In non-exposed men mean background of urinary thioethers was 6.05 mmol SH/mol creatinine (n = 56). In applicators exposed to soil fumigants containing DCP, urinary excretion of thioethers followed first order elimination kinetics. Urinary half lives of elimination of thioethers were 8.0 (SD 2.5) hours based on excretion rates and 9.5 (SD 3.1) hours based on creatinine excretion. The urinary half life of elimination of thioethers was almost twofold higher compared with half lives of elimination of the mercapturic acids of Z- and E-1,3-dichloropropene. The post- minus pre-shift thioether concentrations in urine and the cumulative urinary thioether excretions correlated well with exposure to DCP. In urine samples the mean thioether concentration was 1.38 higher than mean DCP mercapturic acid concentration. This suggests the presence of unidentified thioether metabolite(s) due to exposure to soil fumigants containing DCP. According to the present data, an eight hour time weighted average exposure to the Dutch occupational exposure limit of 5 mg/m(3) DCP results in a post- minus pre-shift thioether concentration of 9.6 mmol SH/mol creatinine (95% confidence interval (95%CI) 7.4-11.8 mmol SH/mon creatinine) and in a cumulative thioether excretion of 139 micromol SH (95% CI 120-157 micromol SH). It is concluded that the thioether assay can be used to assess comparatively high levels of exposure to DCP. PMID- 1854653 TI - Exposure to benzene and mortality from leukaemia: results from coke oven and other coal product workers. PMID- 1854652 TI - Increased erythrocyte volume in car repair painters and car mechanics. AB - The biological effect of occupational long term low level exposure to organic solvents was studied in 17 car repair painters and 28 car mechanics, and compared with a control group consisting of 46 healthy men not exposed to organic solvents. The erythrocyte count (RBC) was significantly decreased for both the painters and the mechanics compared with the control group, and a significant increase in the mean erythrocyte volume (MCV) was seen in painters. The mode in size distribution of the erythrocytes (MAXRBC) was shifted towards larger cell volumes for both painters and mechanics. When data from painters and mechanics were combined, the exposed group showed a significantly reduced erythrocyte count (RBC), an increased mean erythrocyte volume (MVC), and an increased mean platelet volume (MPV) compared with the controls. Exposure measurements in combination with analysis of haematological parameters may be a tool for early detection of cellular changes in the blood caused by exposure to solvents, before the appearance of clinical symptoms. PMID- 1854654 TI - Bootstrap estimate of the variance and confidence interval of kappa. PMID- 1854655 TI - The treatment of coronary artery disease in the elderly. AB - Changing population demographics dictate that in the next decade physicians will be increasingly faced with treating coronary artery disease in the elderly. Despite this, there is a paucity of data to guide management decisions in this population. Currently, it appears that "low-risk" or mild coronary artery disease can be treated medically so long as appropriate adjustments are made for aging changes in renal function, hepatic metabolism, noncompliance, multisystem disease, etc. Unfortunately, most elderly patients have "high-risk" or severe coronary artery disease. Balloon dilatation can yield excellent results in certain highly selected "high-risk" patients, but its role in the frequently encountered multivessel disease patient is unclear until current studies are completed. Coronary bypass grafting in selected patients clearly prolongs survival, but careful patient selection and meticulous preoperative and postoperative is required. Finally, the importance of issues such as quality of life, function independence, and cost must be addressed in more detail if physicians are to make rational decisions in treating this expanding population. PMID- 1854656 TI - Effect of a bradycardic agent on the isolated blood-perfused canine heart. AB - Bradycardic agents could limit the consequences of myocardial ischemia via two mechanisms: by decreasing myocardial oxygen demand (MVO2) and by increasing diastolic coronary blood flow (CBF). We investigated whether the benzazepinone UL FS 49 affects only sinus node cells or also smooth muscle and/or myocardial cells. To avoid confounding interactions with the periphery, we performed experiments on 11 isolated, blood-perfused canine hearts. Injection of UL-FS 49 (1 mg/kg i.c.) significantly reduced heart rate (HR) from 104 +/- 7 to 93 +/- 7 min-1 (mean +/- SEM) and increased stroke volume (n = 6: 9.8 +/- 1.1 vs. 13.2 +/- 1.6 ml), so that cardiac output remained unchanged (n = 6: 1.1 +/- 0.1 vs. 1.2 +/ 0.1 l/min). The contractile state, assessed by isovolumic peak systolic pressure, was unaltered by UL-FS 49 (n = 5: 72 +/- 6 vs. 72 +/- 6 mmHg). At a constant coronary arterial pressure (CAP) of 80 mmHg, mean CBF was slightly decreased (102 +/- 11 vs. 97 +/- 10 ml/[min.100 g]) by UL-FS 49, such that mean coronary resistance remained unchanged (0.9 +/- 0.1 vs 1.0 +/- 0.1 mmHg.min.100 g/ml). The slight decreases in arteriovenous oxygen content difference (n = 6: 6.6 +/- 0.7 vs. 6.5 +/- 0.7 ml/100 ml) and in CBF lead to a calculated, significant decrease in MVO2 (n = 6: 6.9 +/- 0.5 vs. 6.0 +/- 0.4 ml.100 g/min). In conclusion, UL-FS 49 at the dose used decreases MVO2 by reducing HR in isolated canine hearts. In the absence of negative inotropic and vasodilating effects, cardiac output is maintained via increased stroke volume, and CAP will likely be preserved in situ. Thus, this specific bradycardic agent could be useful in treating ischemic myocardial disease. PMID- 1854657 TI - Protective effects of felodipine and verapamil against imipramine-induced lethal cardiac conduction disturbances in the anaesthetized rat. AB - The effect of verapamil and felodipine on imipramine-induced cardiac toxicity was assessed in anaesthetized rats. Rats received either infusion of saline (n = 13), or non-hypotensive doses of felodipine (n = 36) or verapamil (n = 36) over 40 minutes. In saline-pretreated rats IV bolus injection of imipramine (10 mg/kg) resulted in severe hypotension, bradycardia, electromechanical dissociation, and death within 3 minutes. Rats pretreated with nonhypotensive doses of felodipine (1, 3, 6, and 10 micrograms/kg/min) or verapamil (10, 30, 100, and 300 micrograms/kg/min) survived throughout the experiment, despite an initial fall in blood pressure within the first 5 minutes after imipramine administration. Blood pressure returned to baseline levels within 15 minutes. Intermittent ECG monitoring showed significant prolongation of QRS duration after imipramine in both saline (by 138%) and verapamil-pretreated rats (by 63%), whereas in the rats pretreated with felodipine no prolongation was observed (+3%). We conclude that, in our experimental model, felodipine, more than verapamil, protects against the cardiac effects of imipramine intoxication. PMID- 1854658 TI - Pulmonary edema during cardiac catheterization successfully treated with bolus administration of nicardipine. AB - This report describes a 62-year-old patient with ischemic dilated cardiomyopathy who presented pulmonary edema during cardiac catheterization. Bolus administration of nicardipine (5 mg in 5 min) into the pulmonary artery determined prompt recovery from the crisis and optimal hemodynamic conditions for completion of the catheterization. The action of the drug was mediated by the rapid reduction of the left ventricular preload and afterload. We believe that bolus administration of nicardipine is useful in treating episodes of acute left ventricular insufficiency. PMID- 1854659 TI - Terminology of torsades de pointes. AB - Marked prolongation of the QT interval may be associated with life-threatening ventricular tachycardia. The ventricular tachycardia has a polymorphous appearance and is usually induced by antiarrhythmic drugs. This peculiar type of ventricular tachycardia was termed by Desserstenne torsades de pointes because of its twisting ORS axis. The main reason to give this entity a special name that differentiates it from other types of ventricular tachycardia is the unique therapeutic approach to its treatment. Torsades de pointes can be suppressed by interventions that shorten the QT interval by increasing the heart rate, such as ventricular or atrial pacing, isoproterenol infusion, or atropine. Recently intravenous magnesium was also shown to be extremely effective. If torsades de pointes is treated as a conventional ventricular tachycardia by drugs that may further prolong the QT interval, it may lead to fatal results. To draw the attention of physicians to this unusual form of ventricular tachycardia, we suggest that the term torsades de pointes be kept. This specific diagnosis will hopefully guide the treating physician in selecting the appropriate mode of therapy. PMID- 1854660 TI - Torsades de pointes: prevention and therapy. AB - Torsades de pointes (TdP) is a life-threatening ventricular tachycardia that occurs in the setting of a prolonged QT interval and is most frequently related to administration of antiarrhythmic drugs. Patients with organic heart disease, with low serum electrolyte levels, with a previous episode of TdP and with bradycardia or baseline QT prolongation may be at increased risk of developing TdP. After initiation of a QT prolonging therapy, the dosage should be modified if the QT interval reaches 560-600 ms. Cessation of medication and immediate hospitalization are indicated in the presence of lightheadedness, syncope, or increased frequency and complexity of ventricular premature beats. The conventional therapy of TdP with isoproterenol or cardiac pacing, although usually effective, has certain disadvantages. Isoproterenol is contraindicated in patients with hypertension or ischemic heart disease, whereas institution of cardiac pacing requires skilled personnel and fluoroscopy. Recently, infusion of magnesium sulfate has been shown to abolish TdP both in the clinical and experimental setting. Compared with conventional therapy, magnesium sulfate has the advantage of safety and simplicity of its administration. In doubtful cases, if does not aggravate a ventricular tachycardia that is not TdP, as may occur with isoproterenol. This advantage and the prompt effectiveness of the drug in four clinical series, including 31 patients, support the use of magnesium sulfate as the first line of therapy for TdP. PMID- 1854663 TI - Modern concepts of reperfusion injury in the ischemic heart disease. PMID- 1854662 TI - Torsades de pointes and early afterdepolarizations. AB - It is suggested that torsades de pointes may be only one of a group of arrhythmias that are characterized by being pause induced or bradycardia induced. A distinction is made between the cause of the "twisting of the points" and the cause of the action potentials that initiate and sustain the tachycardia. It is pointed out that torsades de pointes and other pause-induced arrhythmias share many features with rhythmic activity arising from early afterdepolarizations. Both are seen after pauses or at low rates, both are seen in quinidine intoxication, and both are seen in hypokalemia. The short-long-short sequence that is seen in torsades de pointes and certain other pause- or bradycardia induced arrhythmias can be fully explained by the behavior of rhythmic activity initiated and sustained by early afterdepolarizations, as can the abrupt onset and termination of pause-induced arrhythmias and their tendency to show initial warming up and terminal slowing down. PMID- 1854664 TI - Reperfusion injury--fad, fashion, or fact? PMID- 1854661 TI - QT-interval prolonging drugs: mechanisms and clinical relevance of their arrhythmogenic hazards. AB - The antiarrhythmic principle of drug-induced QT-interval prolongation is well known. However, with the widespread use of the presently known and new Class III antiarrhythmic agents under investigation, and the growing number of agents not primarily designed as antiarrhythmic drugs that potentially cause QT prolongation, we have also become aware of the proarrhythmic hazards associated with many of these agents. The proarrhythmic risk differs markedly from one agent to another and interferes with many individual clinical variables (e.g., hypokalemia, sinus bradycardia). This paper summarizes the present data on the proarrhythmic risk of drug-induced QT prolongation, including the value and problems of the rate-corrected QT interval, the mechanisms involved in the genesis of proarrhythmia, and the clinical cofactors that facilitate the occurrence of proarrhythmic events. In addition, an extensive database provides information on the known proarrhythmic risk of all currently used QT-prolonging agents. PMID- 1854665 TI - Reperfusion-induced injury: a possible role for oxidant stress and its manipulation. AB - While some investigators recognize "reperfusion-induced injury" as an important component of the overall injury that occurs during ischemia and reperfusion, others question its existence. Resolution of this controversy is of considerable importance, particularly in an era of thrombolysis, since reperfusion-induced injury might be amenable to treatment. Although reperfusion is an absolute prerequisite for the recovery of ischemic tissue, it undoubtedly has some unfavorable effects. The identification of four (possibly sequential) components of reperfusion-induced injury helps to clarify the situation: a) Reperfusion after brief periods of ischemia can trigger arrhythmias in tissue that is potentially salvable; there is abundant experimental and clinical evidence for this form of reperfusion injury. b) Reperfusion may also be associated with "myocardial stunning"; however, given sufficient time, this prolonged postischemic contractile and metabolic dysfunction will recover. There is good experimental evidence and some clinical evidence for the existence of this type of reperfusion-induced injury. c) Reperfusion is commonly thought to cause lethal injury in cells that, until the time of reperfusion, were potentially salvable. However, conclusive evidence that reperfusion can kill cells does not yet exist. d) Reperfusion may alter the nature of necrotic processes in tissue that has already sustained lethal injury, while not altering the number of cells that die this may change the manner in which they die; this form of reperfusion injury could lead to differences in scar formation and vulnerability to aneurysm. There is considerable evidence for the existence of this form of reperfusion-induced injury. Many candidate mechanisms have been proposed for each form of reperfusion injury. Ionic disturbances (particularly for calcium) are often cited and, most recently, free radical-induced induced injury (oxidant stress) has been suggested as important. Considerable evidence exists that oxidant stress is involved in stunning and in reperfusion-induced arrhythmias, and characterization of underlying mechanisms might lead to novel therapeutic principles, such as antioxidant therapy. However, much remains to be learned. PMID- 1854666 TI - Role of calcium and other ions in reperfusion injury. AB - Calcium-related mechanisms may play a role in several aspects of reperfusion injury. One proposal is that internal cytosolic calcium concentration is elevated early in the reperfusion period and that excess oscillations of calcium can very significantly contribute to reperfusion ventricular arrhythmias. Alternate hypotheses, such as those involving free radicals and the local tissue renin angiotensin system, can be married to the existing hypothesis. Furthermore, the hypothesis allows for a role of the sodium-calcium exchange system and the proton sodium exchanger. The hypothesis also provides an explanation for "stunning," as it is proposed that early excessive cytosolic calcium damages the organelles regulating the contractile cycle, which subsequently develops into imperfect functioning of the contractile apparatus. Calcium antagonist drugs given during the ischemic period may lessen reperfusion injury by decreasing the severity of ischemic damage. When given at the time of reperfusion, results are complex and to some extent conflicting. The biggest challenge is to understand how relatively low doses of calcium antagonists given after the onset of reperfusion help to decrease delayed reperfusion "stunning." A logical but untested proposal is that calcium antagonists help to prevent delayed contraction-band necrosis, one of the causes of delayed no-reflow. PMID- 1854669 TI - Clinical experience of coenzyme Q10 to enhance intraoperative myocardial protection in coronary artery revascularization. AB - Seventy-eight patients undergoing coronary artery bypass grafting (CABG) were compared retrospectively to evaluate whether pretreatment with coenzyme Q10 (CoQ) is effective in preventing left ventricular depression in early reperfusion following CABG. CoQ (5 mg/kg, intravenously) was given to 60 patients, 2 hours prior to the onset of cardiopulmonary bypass (CPB). CABG was performed using saphenous vein under CPB associated with cold cardioplegia in the standard fashion. Heart rate, mean arterial pressure, and cardiac index showed no significant difference between the CoQ and control groups. However, left ventricular stroke work index was significantly elevated at 6 and 10 hours of reperfusion following CABG in the CoQ-treated group compared with the controls. Serum MB-CK was lower at 0 and 6 hours of reperfusion in the CoQ group compared with the controls. These results suggest that pretreatment with intravenous CoQ is effective in preventing left ventricular depression in early reperfusion and in minimizing myocardial cellular injury during CABG followed by reperfusion. PMID- 1854668 TI - The occurrence of oxidative stress during reperfusion in experimental animals and men. AB - Reperfusion is the prerequisite for the ischemic myocardium to recover its metabolic and mechanical function. However, reperfusion after a prolonged period of ischemia in the experimental animal may exacerbate, or at least accelerate, the occurrence of ischemic injury, whilst in humans at the least it is not beneficial. This entity has been called reperfusion damage, since much of the damage is believed to be caused by events occurring at the moment of reperfusion rather than by changes occurring during ischemia. The existence of reperfusion damage, however, has been questioned, and evidence in favour of the concept is sparse. At the moment the molecular events occurring at the time of reperfusion are not completely understood, and the relative importance of several proposed deleterious mechanisms is not yet established. One of the most fashionable ideas for the cause of reperfusion damage is that the function of cell membrane is modified by oxygen radicals generated at the moment of reperfusion. Evidence in favour of and against this hypothesis is described in detail in the present article. PMID- 1854670 TI - Effect of orally administered alpha-tocopheryl acetate on human myocardial alpha tocopherol levels. AB - Free radical injury may contribute to the delayed postoperative recovery of myocardial metabolism and ventricular function after elective coronary artery revascularization. This clinical study was designed to evaluate, in stable angina patients having aortocoronary bypass surgery, whether orally administered alpha tocopheryl acetate was effective in increasing myocardial alpha-tocopherol levels and the effect of cardioplegic arrest followed by reperfusion on the myocardial alpha-tocopherol levels. Twenty-four patients with stable angina pectoris for elective revascularization received preoperatively the natural stereoisomer of alpha-tocopheryl acetate labelled with deuterium (D3) and six patients were used as controls. Since four patients who received 300 mg of D3-alpha-tocopheryl acetate preoperatively for 1 and 2 days did not have significant increases in their myocardial total or D3-tocopherol levels, the remaining 20 patients received 100 mg (n = 6), 300 mg (n = 8), or 900 mg (n = 6) of D3-alpha-tocopheryl acetate for 14 consecutive preoperative days. The left ventricular deuterated and nondeuterated alpha-tocopherol levels were measured by gas chromatography/mass spectrometry. Although there was a decrease (p less than 0.05) in myocardial alpha-tocopherol levels with the onset of reperfusion (cross-clamp removal), the myocardial tocopherol levels were not statistically different from preoperative levels by 20 minutes of reperfusion. At least 300 mg of alpha-tocopherol must be taken orally for 14 consecutive days to double the myocardial alpha-tocopherol levels. PMID- 1854671 TI - Modelling of oxygen transport in systemic circulation in a hyperbaric environment. AB - A mathematical model is developed for analysing the transport of oxygen in the systemic capillaries and surrounding tissue in a hyperbaric environment. The governing equation in the capillary describes the transport due to molecular diffusion (radial as well as axial) and the convective effect of the blood. The non-linear oxygen dissociation curve is represented by a linear function simulating the conditions of a hyperbaric environment. The corresponding equation in the tissue region is based on the transport of oxygen due to radial as well as axial diffusion and the zero order metabolic consumption rate. The equations in both the regions are connected through the interface conditions. An analytical solution of the resulting system of elliptic partial differential equations with the physiologically relevant boundary conditions is obtained by the method of eigenfunction expansion. It is found that the amount of oxygen decreases from the core of the capillary to the periphery of the tissue. It is shown that significant radial diffusion of oxygen takes place in the initial part of the tissue close to the arterial end. The accumulation of oxygen in the tissue has been examined in terms of various non-dimensional parameters. The physiological relevance of these parameters in determining the degree of accumulation of O2 in the tissue in a hyperbaric environment is discussed in the light of previous experimental studies. PMID- 1854667 TI - Oxygen-derived free radicals and myocardial reperfusion injury: an overview. AB - Reperfusion of acutely ischemic myocardium is associated with various distinctive pathophysiologic derangements, which are collectively referred to as reperfusion injury. Among these, three have been attributed to oxygen radicals: a) arrhythmias, b) transient mechanical dysfunction ("stunning"), and c) cell death. a) Reperfusion-induced arrhythmias. Although the precise mechanism for reperfusion arrhythmias remains to be determined, considerable evidence suggests that oxygen radicals play an important pathogenetic role in these rhythm disturbances. b) Transient mechanical dysfunction ("myocardial stunning"). Studies suggest that this abnormality is caused by events occurring in the initial seconds of reperfusion, and therefore represents a manifestation of sublethal, reversible reperfusion injury. Although our understanding of the mechanism of myocardial stunning is still fragmentary, there is overwhelming evidence for a pathogenetic role of oxygen radicals. c) Cell death. The evidence that reperfusion causes extension of the infarct produced by the antecedent ischemia is highly controversial. Although several studies have reported reduction of infarct size with antioxidants applied at the time of reperfusion, numerous other investigations have failed to reproduce these results. At present, there is no obvious explanation for this discrepancy. What is clear is that short term administration of antioxidants at the time of reperfusion will not produce sustained limitation of infarct size. However, the possibility that long-term administration of antioxidants will produce sustained limitation of infarct size merits further consideration. In conclusion, there is strong evidence that the generation of oxygen radicals upon reperfusion plays an important pathogenetic role in two manifestations of reperfusion injury, namely, arrhythmias and stunning. Intense controversy persists regarding whether oxygen radicals contribute to extending cell death upon reperfusion and whether reperfusion in itself causes cell death. On the basis of the evidence available at this time, oxygen radicals appear to be important in the genesis of relatively mild, sublethal forms of myocellular damage, but their role in the genesis of lethal myocellular injury remains to be established. PMID- 1854672 TI - Status of medical engineering technology assessment in Japan. AB - Today in Japan, although the installation rates of high level medical engineering (ME) equipment at hospitals and clinics are the highest in the world, actual and effective technology assessment programs are lacking. In this paper, the author introduces the unique situation and tendency of ME in Japan as compared to western countries and also discuss the role which ME has played in this transition of the health care system. Furthermore the author introduces a developing program for ME technology assessment (MTA) recently investigated in Japan. PMID- 1854673 TI - A method of measuring the peak flow rate and the regurgitant volume of regurgitation based on the characteristics of turbulent free jets. AB - The issuing flow rate of a jet, Q0, is given by Q0 = U0A, where U0 is the issuing velocity of the jet and A is the cross-sectional area of the orifice. However, measurement of A of a regurgitant jet in the cardiovascular system is difficult. On the assumption that the jet is 'free' and turbulent, the following relations apply between the diameter of the orifice D, the length of the core region of the jet L, the centerline velocity of the jet Uc(chi) at an arbitrary distance chi(greater than L) from the orifice, and U0:L = 6.8D and Uc(chi)/U0 = L/chi. From these equations we obtain Q0 = 0.017 (chi Uc(chi))2/U0. Pulsatile jets issuing into an aqueous glycerol bath through orifices with various diameters were studied. U0, chi and Uc(chi) were measured with a color Doppler system. There was a good linear correlation between the peak flow rates estimated from the above equation and those measured with a flowmeter irrespective of the diameter of orifices (y = 0.93 chi + 3.8, r = 0.95, SEE = 6.6 ml/s). Assuming that the flow rate waveform is similar to the issuing velocity waveform, we estimated the issuing volume per stroke by integrating the issuing velocity. There was a good linear correlation between the estimated issuing volume and the known stroke volume of the pump (y = 1.0 chi + 2.6, r = 0.92, SEE = 2.8 ml). PMID- 1854674 TI - Enhancement of fracture healing by specific pulsed capacitively-coupled electric field stimulation. AB - The histologic procedure technique was used to evaluate the bone fracture healing rate of manually fractured fibulae after they were submitted to several different types of capacitively-coupled electric field stimulation, classified depending on the parameters of peak-to-peak voltage, frequency and duration. Using a completely randomized design, 30 New Zealand male rabbits were divided into six different groups: a control group, a 60 kHz and 220 mVp-p sine wave group as proposed by Brighton in 1985, and four special parameters of pulse wave groups. After comparing these different types of electrical stimulation, the group with the parameters of a pulse train repetition frequency of 15 Hz, a pulse frequency of 10 kHz and 5 V peak-to-peak intensity experienced the same enhancement of bone fracture healing as the group with the parameters suggested by Brighton in 1985. PMID- 1854675 TI - Low birth weight and a family history of schizophrenia predict poor premorbid functioning in psychosis. AB - Risk factors thought to predispose to schizophrenia, and premorbid functioning, were assessed blind to diagnosis by interviewing the mothers of 73 patients with DSM-III schizophrenia or affective psychosis. Higher risk of schizophrenia in relatives, lower mean birth weight, a more frequent history of obstetric complications, and poorer educational achievement distinguished the patients with schizophrenia from those with affective psychosis. Low birth weight and obstetric complications each predicted childhood schizoid and schizotypal traits. Poor social adjustment between ages 5 and 11 was predicted by low birthweight and by a family history of schizophrenia. PMID- 1854676 TI - A clinical study of schizophrenic suicides. 42 cases in Taiwan. AB - A clinical study of 25 male and 17 female schizophrenic suicides is presented. Jumping from a height was the most common method used. The 42 suicidal schizophrenics in Taiwan were compared with both 84 sex- and age-matched and 60 5 year illness course non-suicidal schizophrenic control groups. The suicidal schizophrenics were not significantly different from the non-suicidal counterparts of both control groups with regard to age, sex, ethnicity, religion, educational background, the presence of suicide cases in the family history, and the presence of insight, but were significantly different in characteristics of a history of previous suicide attempts, presence of psychotic symptoms during their final month, depression during their final month, a history of depression, a history of previous psychiatric hospitalizations, and the number of hospitalizations. We discuss the findings from this study and others in the literature in the context of the different clinical and socio-cultural backgrounds of these Taiwanese schizophrenic suicides. PMID- 1854677 TI - Positive and negative symptoms of schizophrenia. Their course and relationship over time. AB - Recent approaches to subtyping schizophrenia have made use of the concepts of positive and negative symptoms. It is sometimes assumed that positive and negative symptoms are distributed discontinuously or inversely. Many of the studies that have examined this concept are cross-sectional. This research examines the relationships among positive and negative symptoms in a sample of 41 DSM III diagnosed schizophrenics. Using the SANS and the SAPS, symptoms are assessed, first, in the acute phase of the illness and then, 6 months later, in a period of relative remission. Results showed that positive and negative symptoms were not inversely related at either phase of the illness. Secondly, in comparison to positive symptoms, negative symptoms were highly intercorrelated at both times. Thirdly, the presence of negative symptoms in the acute phase was highly predictive of the presence of negative symptoms at follow-up. Implications for the longitudinal course of symptoms in schizophrenia are discussed. PMID- 1854678 TI - Prostaglandin E1 suppression of platelet aggregation response in schizophrenia. AB - The inhibitory effects of prostaglandin E1 (PGE1) on the platelet aggregation response (PAR) to adenosine diphosphate (ADP) in 103 schizophrenics, 55 patients with other mental disorders, and 71 controls were examined. The three groups did not differ in PAR to ADP. However, schizophrenic patients, especially in the acute state, showed a significant reduction in the inhibitory effects of PGE1 on PAR compared to the other two groups. These results suggest PGE1 hyposensitivity exists in some schizophrenic patients, which may result from PGE1 deficiency. As clinical characteristics of the subgroup showing platelet PGE1 subsensitivity, relatively successful heterosexual relations, less anergia, and a more severe activation factor on BPRS were identified. Furthermore, the relationship between platelet sensitivity to PGE1 and brain morphology, using magnetic resonance imaging on 39 male schizophrenics was examined. Of 11 parameters obtained from MRI measurements, only callosum: brain ratio showed a significant negative correlation with a platelet sensitivity to PGE1. The current study suggested existence of a subgroup of schizophrenia having platelet hyposensitivity and a definite clinical feature as state markers and small corpus callosum as a trait marker. PMID- 1854679 TI - Pineal calcification in schizophrenia. Relationship to age of onset and tardive dyskinesia. PMID- 1854680 TI - Leo Vroman, scientist: an appreciation. PMID- 1854681 TI - Festschrift in honor of the 75th birthday of Dr. Leo Vroman: Part I. PMID- 1854682 TI - Vroman effects, techniques, and philosophies. AB - Leo Vroman's work on blood-materials interaction over the years has motivated and influenced much of our work in this field. Here we show how most of our studies on proteins at interfaces can be traced to Vroman's ideas presented in Blood over 25 years ago. Specifically, we briefly discuss simple proteins at simple interfaces, complex interfaces, complex proteins at interfaces, multi-parameter phenomena, and scientific communication and education. PMID- 1854683 TI - Mechanism of the participation of the contact system in the Vroman effect. Review and summary. AB - The contact system comprises three zymogens (factor XII, factor XI, and prekallikrein) and the non-enzymatic activation cofactor, high-molecular-weight kininogen (HK). When blood comes into contact with negatively charged surfaces, a small amount of factor XII is adsorbed and activated which, in turn, generates kallikrein from prekallikrein. Kallikrein amplifies the activation of the contact system by producing additional factor XIIa molecules as well as by activating the cofactor, HK, to HKa. HKa, while complexed with either prekallikrein or factor XI, can penetrate a barrier of fibrinogen and adsorb to the surface, where it optimally positions these zymogens for activation by adjacent factor XIIa molecules. Factor XIa can then degrade the light chain of HKa, producing the inactive cofactor HKi, which no longer has the ability to adsorb to a surface or support coagulation. The Vroman effect refers to the 'conversion' of fibrinogen from plasma on a negatively charged surface. Fibrinogen is detectable within seconds after normal plasma contacts the surface but, within minutes, is undetectable. On the other hand, HK, although not initially detectable on the surface, is found at later times when fibrinogen is no longer visible. However, in plasma lacking factor XII or HK, fibrinogen remains detectable at times when it is undetectable in normal plasma. The phenomenon of the Vroman effect is explained by the mechanism of surface-dependent activation of factor XII, which both directly and indirectly (through the formation of kallikrein) generates HKa from HK. HKa (but not HK) displaces fibrinogen from the surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854684 TI - Why proteins prefer interfaces. PMID- 1854685 TI - The Vroman effect in tube geometry: the influence of flow on protein adsorption measurements. AB - The transient adsorption of fibrinogen from plasma (a manifestation of the Vroman effect), due in large part to displacement by trace proteins such as high molecular-weight kininogen (HK), factor XII, and plasminogen, has traditionally been studied in nonflowing systems in this laboratory. This paper reports new data on adsorption in tubing geometry under laminar flow. Fibrinogen adsorption from human blood plasma and whole blood diluted to varying exents was measured on glass and polyethylene tubing. The presence of flow did not change the nature of the Vroman effect, except that the processes of adsorption and displacement, which are typically diffusion-limited in static systems, were augmented by convective transport. At the highest applied shear rates of 408 and 510 s-1, the initial adsorption rate of fibrinogen was estimated to be 5.0 X 10(-5) cm/s on both surfaces. The intrinsic rate of displacement of fibrinogen (due to the Vroman effect) at high shear rates was about ten times faster from glass than from polyethylene based on data taken 5 min after the experiment started. The rates of fibrinogen adsorption and displacement were not observed to be significantly augmented by the cellular elements of whole blood at dilutions exceeding 20:1. The consistently observed axial dependence of adsorption in static and flow experiments in tubing geometry was investigated. It was concluded that the effect results, under most conditions, from the creation of a concentration boundary layer during the displacement of the equilibrating buffer by the injected protein solution. The possibility of local depletion due to rapid adsorption during injection or the final displacement of the protein solution was concluded to make lesser contributions to axial variations in measured adsorption. PMID- 1854686 TI - Surface exclusion and molecular mobility may explain Vroman effects in protein adsorption. AB - Data on protein adsorption usually show that for increasing surface coverage the adsorption velocity decreases much faster than linearly. This contrasts to the classical Langmuir model with an adsorption velocity proportional to the number of unoccupied binding sites. It has been shown that this non-linearity may explain phenomena like transient adsorption of different proteins from a protein mixture or dilution-dependent changes in binding properties, collectively called Vroman effects. However, the molecular mechanisms explaining this non-linear behavior remain to be established. A Monte Carlo simulation model is presented that incorporates steric hindrance, lateral mobility and mutual interactions of adsorbed molecules. Experimental data on the adsorption kinetics of prothrombin and annexin V, a recently discovered anticoagulant protein, at phospholipid bilayers are analyzed with this model. A major conclusion is that the steep decline in adsorption rates for increasing surface coverage can be explained, without assuming repulsive forces between adsorbed molecules, as a surface exclusion effect combined with lateral mobility of adsorbed molecules. The fact that annexin V shows this effect to a much lesser degree than prothrombin is tentatively explained by clustering of adsorbed annexin V molecules. A qualitative effect of lateral mobility on the adsorption characteristics, predicted by the model, is confirmed in experiments in which the fluidity of the bilayers was manipulated. PMID- 1854687 TI - The effects of temperature and buffer on fibrinogen adsorption from blood plasma to glass. AB - [125I]-Fibrinogen was used to measure the adsorption of fibrinogen from baboon plasma to two types of glass (Pyrex and a borosilicate glass) at 25 and 37 degrees C using two different buffers to dilute the plasma, the first being citrate-phosphate buffered saline (CPBSz) and the second isotonic Tris-saline (TRIS), both pH 7.4. In addition, the effects of hydration conditions, rinsing techniques, and glass-cleaning treatments on fibrinogen adsorption were evaluated. The data reveal that lower temperatures and the use of TRIS to dilute the plasma significantly enhance fibrinogen adsorption to both types of glass. As has been observed in the past, fibrinogen adsorption peaked at intermediate plasma concentrations on both Pyrex and borosilicate glass (the so-called Vroman effect), but almost twice as much fibrinogen adsorbed to glass when TRIS was used to dilute the plasma instead of CPBSz. Moreover, up to five times as much fibrinogen adsorbed to both types of glass at 25 degrees C compared with 37 degrees C. No effects of the rinsing technique or glass-cleaning treatment were observed. PMID- 1854688 TI - Laser beam clipping: two aspects and a safety device. PMID- 1854689 TI - Iris clipping of a diode laser beam when performing retinal photocoagulation. AB - The Microlase infrared diode laser has recently become available for retinal photocoagulation. It uses a laser beam with a large convergence angle (23 degrees). This gives rise to a laser beam with a relatively large cross section at the subject's pupil. In this study the pupillary area required to view the fundus at the slit-lamp with a 90-dioptre lens is determined. It is found that the pupillary area required to view the fundus is smaller than the cross section of the Microlase laser beam at the pupil. Thus iris clipping of the laser beam can occur even though the surgeon has a clear and bright view of the fundus. Care should be taken to use the Microlase only in the presence of a widely dilated pupil. PMID- 1854690 TI - Ultrastructural pathology of the 'barrier sites' in experimental autoimmune uveitis and experimental autoimmune pinealitis. AB - Lewis rats were immunised with retinal S-antigen to induce experimental autoimmune uveitis and experimental autoimmune pinealitis. The blood-retinal and blood-pineal 'barrier sites' were examined by transmission electron microscopy. Inflammatory cell movement through Bruch's membrane involved separation of its constituent layers, cell migration through pores in the membrane, and between retinal pigment epithelial cells without causing significant displacement of the retinal pigment epithelial cell layer. The endothelial cells of retinal and pineal vessels with perivascular infiltrates showed morphological features resembling endothelium of 'high endothelial venules'. PMID- 1854691 TI - Review of fluorescein angiograms performed in one year. AB - In this study 374 consecutive fundus fluorescein angiograms (FFAs) were performed on 330 patients. Of these, 165 (50%) were investigated for age related maculopathy. In only 12% did this investigation lead to an alteration in treatment. The remaining 50% of angiograms were requested for diabetic patients (15%), retinal vein occlusion (5%), tumours (6%), and various other disorders. In the diabetic patients treatment could have proceeded without FFA in 24% of patients who underwent it. Missed diagnoses corrected by angiography and areas where unnecessary angiograms were performed were identified. One interesting subgroup of eight patients with unexplained loss of central vision was identified. Careful clinical examination had failed to reveal any abnormality. FFAs were of no diagnostic value in these patients. PMID- 1854692 TI - North Carolina's dominant progressive foveal dystrophy: how progressive is it? AB - We studied 34 family members at risk of having dominant progressive foveal dystrophy of Lefler, Wadsworth, and Sidbury (also called North Carolina macular dystrophy) and found 17 to be affected. Fifteen of these affected subjects were observed over at least a 10-year period for evidence of progressive macular degeneration. Only one subject showed objective evidence of progressive deterioration in only one eye. Our findings further substantiate that this dystrophy generally has a stable course, contrary to its original description. PMID- 1854694 TI - Emmetropisation, squint, and reduced visual acuity after treatment. AB - In a sample of children used to assess the value of optical correction of hypermetropia from the age of 6 months the refraction of the most hypermetropic meridian frequently became less than 3.5 D as the children grew. When this occurred, the incidence of squint was significantly less (p less than 0.001) and the last known acuity after treatment was significantly better (p less than 0.001) than when it did not. This process of emmetropisation appears to have been impeded by the consistent wearing of hypermetropic spectacle correction from the age of 6 months. PMID- 1854693 TI - Cis-platinum chemotherapy for ocular basal cell carcinoma. AB - We have used intravenous cis-platinum chemotherapy in the treatment of three patients with basal cell carcinoma of the lid extending into the orbit. Cis platinum chemotherapy caused a reduction in tumour size and thereby delayed surgery in all cases. It allowed for local resection in one case, appeared to delay a patient's exenteration in a second case, and was used prior to radiotherapy in a third case. While not curative, cis-platinum may be useful as an adjuvant to decrease tumour mass prior to local excision and for patients who refuse or must delay exenteration. PMID- 1854695 TI - Comparison of retrobulbar and periocular injections of lignocaine by computerised tomography. AB - Ten patients undergoing cataract surgery were given a local anaesthetic with lignocaine solution which was mixed with iohexol contrast medium. The location of the needle and the substance injected was determined by computerised tomography following retrobulbar or periocular anaesthesia. The retrobulbarly inserted needles were within the muscle cone, directed towards the optic foramen. The periocular needles were outside the muscle cone, tangentially along the orbital floor or pointing slightly upwards. After the retrobulbar injection the contrast medium was seen within the cone immediately after the injection and outside the cone as early as 3 minutes after the injection. With the periocular technique, however, diffusion of the anaesthetic in the opposite direction (that is, into the muscle cone) was rapid. The contrast medium was identified inside the muscle cone 2 minutes after the injection. Compression with an intraocular pressure reduction device after both of these techniques prevented exophthalmos. It is concluded that retrobulbar-like anaesthesia can also be induced by an appropriate periocular technique. PMID- 1854696 TI - Experimental Acanthamoeba keratitis: II. Immunohistochemical evaluation. AB - In a Wistar rat experimental model of Acanthamoeba keratitis immunohistochemical techniques were used to analyse the host cellular response. The inflammatory cell profile was observed to change at intervals. In tissue sections the cellular response consisted of neutrophils on the first day but predominantly macrophages on the following days. Some T lymphocytes but no B lymphocytes were observed. PMID- 1854697 TI - Childhood blindness in the Republic of Ireland: a national survey. AB - We completed a national study of blindness in children under 16. Approximately 80% of the blind children (that is, with vision of 3/60 or less) in the Republic of Ireland (172 children) were seen, 93 males and 79 females. The survey was carried out between July 1989 and June 1990. It is the first such study to be carried out. Ninety seven (56%) children had lesions due to factors acting before the perinatal period. Of these, 28 (16% of the total number surveyed) had lesions due to genetic causes; 69 (40%) had lesions due to factors operating in the prenatal period other than genetic factors. Forty six (27%) had lesions due to factors acting in the perinatal period. Twenty two (13%) had lesions due to factors acting in childhood. (4% could not be categorised in this way). The commonest single primary diagnoses were birth asphyxia in 19 (11%) cases and retinopathy of prematurity in 19 (11%) cases. PMID- 1854698 TI - Intraocular coenurosis: a case report. AB - A case of intraocular coenurosis was clinically diagnosed and treated with praziquantel. The drug destroyed the coenurus, but vision was lost through toxic endophthalmitis and retinal detachment. There were no systemic side effects. PMID- 1854699 TI - Treatable blindness in temporal arteritis. AB - Temporal arteritis is a common cause of blindness. Prompt steroid treatment limits unilateral visual loss while protecting the contralateral eye. Established blindness is irreversible. We report a case of temporal arteritis in which an eye with no light perception secondary to an arteritic anterior ischaemic optic neuropathy regained 6/6 vision. PMID- 1854700 TI - Welding arc maculopathy and fluphenazine. AB - A 45-year-old male patient presented with a bilateral maculopathy following unprotected exposure of less than two minutes' duration to a manual metal arc welding unit. He had been receiving the drug fluphenazine for the previous 10 years for treatment of depression. We believe that the drug fluphenazine, which had accumulated in his retinal pigment epithelium, may have rendered him particularly susceptible to retinal photic damage. PMID- 1854701 TI - Bilateral retinal artery occlusion due to mitral valve prolapse. AB - We report a case of bilateral retinal artery occlusion due to mitral valve prolapse. Most patients with retinal ischaemia in whom it is found have not been previously known to have it. Since it is a common condition it would seem essential that it be included in the differential diagnosis of amaurosis fugax and retinal artery occlusion if future ischaemic events are to be prevented. All patients with retinal ischaemia should have a full cardiovascular examination supplemented by echocardiography. PMID- 1854702 TI - Solitary extramedullary plasmacytoma of the maxillary antrum and orbit presenting as acute bacterial orbital cellulitis. AB - Orbital involvement by plasma cell tumours is rare. Orbital tumours do not generally present as an acute orbital inflammatory disease in adults, though tumours such as rhabdomyosarcoma may cause clinical signs similar to an acute orbital cellulitis in children. We describe a patient with bacterial orbital cellulitis and sinusitis who was found to have an extra-medullary plasmacytoma of the maxillary antrum and orbit and coexisting testicular seminoma. PMID- 1854703 TI - Late onset endophthalmitis associated with intraocular lens: a case of molecularly proved S. epidermidis aetiology. AB - A case of severe endophthalmitis after cataract extraction followed by posterior chamber lens implantation is reported. Microbiological cultures from a tap of the patient's aqueous humour prior to lens explantation as well as from the explanted lens and aqueous and vitreous humour during operation yielded Staphylococcus epidermidis sensu stricto. Scanning electron microscopy showed massive colonisation of the lens loop by staphylococci. Clonal identity of all isolates was demonstrated by plasmid DNA analysis and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of extra-cellular products. This is strongly suggestive of the aetiological role of S. epidermidis in this case of late onset endophthalmitis. PMID- 1854704 TI - Ptosis caused by pachydermoperiostosis. AB - Pachydermoperiostosis is a rare inherited disorder which presents with finger clubbing, facial enlargement, and periostitis. A case is described in which surgery for ptosis was performed and the differential diagnosis of the condition is discussed. The histological and ultrastructural appearances of the eyelids show sebaceous gland hyperplasia and excessive deposition of mucin in the dermis and would suggest that pachydermoperiostosis may be an example of a cutaneous mucinosis. PMID- 1854705 TI - Beam obstruction hazard on Q-switched Nd-YAG ophthalmic lasers: a safety device for the Nanolas laser. PMID- 1854706 TI - Genetic counseling in retinoblastoma. PMID- 1854707 TI - Practical hazards of photic sneezing. PMID- 1854708 TI - Acute multilocular osteomyelitis in infancy and childhood. AB - 38 cases of acute multilocular osteomyelitis out of a total of 165 osteomyelitis patients were treated between 1974 and 1986 at the Department of Paediatric Surgery and Paediatric Diseases at the University of Mainz. Osteomyelitis in infants was separated from juvenile osteomyelitis because of the different problems inherent to this disease depending upon the age; likewise, multilocular remote involvement was separated from regional multiple involvement. It was found that distant involvement is of special importance in infancy. 6 of the 8 cases in this group presented with symmetrical involvement. This interesting phenomenon is described in this article for the first time in acute multilocular osteomyelitis; so far, it was known to occur only in chronic recurrent multifocal osteomyelitis (CRMO). The infants in this group were predominantly newborn who were particularly severely handicapped by predisposing factors such as necessary intensive-care measures or surgical interventions. Our findings showed that in this age group most of the problems occurred, namely: 3 deaths and 2 healing defects in 8 children. For this reason it is imperative to effect particularly close monitoring of multilocular acute osteomyelitis in infancy. This must be considered as a paediatric and paediatric-surgical emergency requiring not only accurate diagnostic measures but also early internistic and surgical treatment to improve the prognosis of this specific disease pattern. PMID- 1854709 TI - Neonatal primary hyperparathyroidism--a case report and review of the literature. AB - Primary Hyperparathyroidism in the neonate is exceptionally rare and is almost invariably fatal unless a prompt diagnosis is made and urgent surgical intervention instituted. The first case was reported in 1947 by Prat et al (30) and since then 35 cases have been published. The true number is probably greater due to the diagnosis being missed both clinically and at autopsy and it has been suggested as a possible contributor to a small number of cases of the Sudden Infant Death Syndrome (17). The authors report on a case presenting in a female neonate, review the world literature and discuss the clinical manifestations, investigators findings and the management options available. PMID- 1854710 TI - Congenital lumbar (Grynfelt-Lesshaft) hernia. AB - Two children with superior lumbar hernias are presented in this report. The first one had many additional anomalies different from the literature and the other one is the second case report of congenital lumbar hernia with posterior meningomyelocele in the literature. Operative repair is recommended for these patients before 12 months of age. PMID- 1854711 TI - Ectopic gastric mucosa in a polyp causing ileo-ileal intussusception: a case report of a three-month-old baby. AB - Ectopic gastric mucosa in the small bowel not associated with Meckel's diverticulum, is rare. Most of the few cases found in the literature are symptomatic and complicated. We report a case of a three month-old baby, the youngest patient reported thus far. He had ectopic gastric mucosa in a polypoid lesion of the mid-ileum, which caused ileo-ileal intussusception. PMID- 1854712 TI - Esophageal pH monitoring: methodology, indication and interpretation. AB - Reflux of gastric contents into the esophagus has for long been accepted as a cause of esophagitis, failure to thrive, and anemia. But, at the same time, gastro-esophageal reflux (GER) is recognized as a physiological phenomenon occurring now and then in every one, especially in the postprandial period. Esophageal pH monitoring is an attractive technique for separating "physiological" from "pathological" GER incidence and duration by measuring incidence and duration. In principle, esophageal pH monitoring is simple, but in practice there are technical and clinical problems. The pH monitoring equipment, the type of electrode, the location of the electrode are examples of equipment and/or methodology related influencing factors. Age, position, duration of the investigation (day/night, fasting/postprandial), feeding and drugs are patient related factors. Despite all these factor, pH data have been shown to be reproducible. The major advantages of pH monitoring are that it evaluates GER in (1) physiological circumstances over (2) a prolonged duration. (3) The investigation can be repeated and can therefore (4) evaluate the efficacy of treatment. (5) The possibility of establishing a relation in time between pH changes and symptoms constitutes another advantage of the technique. PMID- 1854713 TI - Midline dermal sinuses and cysts and their relationship to the central nervous system. AB - Sixty-one children (below 12 years) with midline dermal inclusions of the cranium and spine were operated on at the Red Cross War Memorial Children's Hospital between 1969-1990. The bregmatic area was the most common position for superficial cysts (33). Eight children had sinuses or cysts near the external occipital protuberance, 2 had isolated fourth ventricular cysts and 1 had a cyst in the quadrigeminal plate cistern. Fifteen children had spinal dermal inclusions, 13 of these were in the lumbosacral area, there was 1 sinus in the cervical spine and another in the midthoracic area attached to an intramedullary cyst. Two children had frontal sinuses, one of which was connected to an interhemispheric dermoid cyst and a lipoma of the corpus callosum. A midline swelling or sinus was the most common clinical presentation. Four out of 15 spinal inclusions and 1/11 occipital sinuses had a meningitic history. Five of 11 of the posterior fossa inclusions had raised intracranial pressure and signs suggestive of cerebellar tumor or abscess. Not one of the 33 bregmatic lesions had any connection to the central nervous system. MRI has proved useful in diagnosing both dermal sinuses and cysts, but CT scanning was our standard investigation. Plain x-ray revealed bony abnormalities in only 60% of our patients with spinal sinuses. We feel that all dermal sinuses or cysts in the midline should be surgically explored after CT or MRI scanning. Lesions mistaken for bregmatic cysts have included hemangiomas (4), hamartomas (2), an encephalocele through the anterior fontanelle (1) and lipomas (2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854714 TI - Use of a collagen coated vicryl tube in reconstruction of the porcine esophagus. AB - This experimental study assessed the use of a collagen-coated vicryl mesh tube to reconstruct the esophagus in growing piglets. Initial experiments, in which a segment of thoracic esophagus was excised and replaced by this prosthetic tube, resulted in all the animals succumbing to mediastinitis within the first 3-4 days. This was shown, at post-mortem, to be due to leakage of the prosthesis, secondary to acid reflux, resulting in dissolution of the prosthesis. The collagen-coated vicryl mesh was thereafter treated with glutaraldehyde and in vitro studies showed that the glutaraldehyde-treated material exhibited a higher resistance to 0.01 M HCl at pH 2.0, when compared with untreated material. In addition, the glutaraldehyde-treated material also showed an increased resistance to digestion by bacterial collagenase. Further experiments to reconstruct the cervical esophagus in growing piglets were performed using the revised glutaraldehyde cross-linked collagen coated vicryl mesh tube. All the animals survived the procedure and the prosthesis were leakproof immediately post operatively. The animals, however, developed severe stenosis at a mean of 11 days post-operatively. Attempts at neo-epithelialization of the graft were seen histologically. There was considerable granulation tissue and scar tissue formation on the mediastinal aspect of the graft. It is suggested that collagen coated vicryl mesh tube may find applications in the treatment of esophageal atresia only if the problem of stenosis of the prosthesis can be solved. PMID- 1854715 TI - Morphology of the diaphragmatic muscle in CDH. AB - Muscle tissue from the wall of CDH demonstrated normal muscle structure with normal fibre types. It could be shown that a large fibrotic wall surrounds the muscular defect. PMID- 1854716 TI - Experimental intestinal obstruction in rats. Studies on structure and disaccharidase activities. AB - An experimental model of congenital intestinal obstruction (CIO) was created in rats by means of fetal intrauterine surgery between the 16th and 20th days of gestation. By the use of a microsurgical technique areas at the mid-jejunum or the jejuno-ileal junction were infarcted by coagulation of mesenteric vessels. Gestation was terminated by Cesarean section within 24 hours before expected term to avoid cannibalism. The structure of the intestinal mucosal cells proximal and distal to the CIO at the light microscopy as well as the ultrastructure level was not changed indicating that the surgical method was successful. The activities of the brush border enzymes, maltase and lactase were significantly reduced distal to the obstruction as compared to controls. Proximal to the obstruction lactase was the only enzyme showing reduced activity in comparison to controls. These findings were not dependent on the localization of the obstruction or when it was performed and suggest that CIO causes selective changes of the biochemical properties of the cell membrane. The results are in agreement with the findings of disaccharidase activities in biopsies taken from human infants with CIO and point to the importance of a normal intestinal passage for the development of brush border enzymes. PMID- 1854717 TI - Familial aspects of Hirschsprung's disease. AB - Twenty-eight of 370 patients (14 families) treated for Hirschsprung's disease (HD) over a 34 year period had a family member with histologically proven HD. These 14 represented 4% of the 351 families: more than one affected child per family in 10 (2.8%) and both parent and child in 2 families. Neuronal intestinal dysplasia (NID) in a parent was associated with total colonic aganglionosis in two siblings of one family which suggests a similar genetic inheritance pattern to HD. Aganglionosis extended beyond the rectosigmoid in 61% of the familial group as opposed to 27% of the non-familial group. A significantly higher number of total colonic aganglionosis (TCA) was noted in those with a family history; 11 out of 28 (39%) as opposed to 19 out of 342 (5.6%) without a family history (p less than 0.001). Fifty percent of males with TCA had a family history but in only 2 cases was this transmitted through a female sibling. Although no significant difference was noted between male and female probands, a three times higher incidence of familial occurrence was noted in females with rectosigmoid disease than in males. Progression of length of segment in succeeding generations was noted in two families. Associated anomalies occurred in 16% without familial occurrence and 11% of the familial group. PMID- 1854718 TI - Isolation and partial characterization of mitogenic factors from cementum. AB - Cementum is the mineralized structure through which soft connective tissues are attached to the teeth. It is a unique calcified tissue characterized by a low metabolic turnover, lack of blood supply, and presence of very few cells. However, it contains substances that influence the biological activities of fibroblasts of adjacent soft tissues. We have partially characterized cementum proteins that have mitogenic activity toward fibroblasts. Cementum was harvested from bovine teeth, and mitogenic factors were extracted in 0.5 M CH3COOH. Heparin Sepharose chromatography separated the mitogenic activity into a major and a minor fraction eluted by 0.5 and 2.0 M NaCl, respectively. The distribution of cementum mitogens in heparin-Sepharose fractions was different from that of alveolar bone and other bones. The cementum mitogenic factor eluting with 2.0 M NaCl from a heparin-Sepharose column was shown to be basic fibroblast growth factor (bFGF) on the basis of inhibition by anti-bFGF antibody and Western blots. The 0.5 M NaCl fraction was purified by HPLC with use of a combination of a DEAE 3W column followed by TSK-250 and C18 columns. NaDodSO4-polyacrylamide gel electrophoresis revealed that the purified fraction contained two protein bands with Mr 22,000 and 19,000, and mitogenic activity was associated with the Mr 22,000 species. The activity of this mitogen, designated as CGF, was potentiated by small quantities of plasma-derived serum or epidermal growth factor. It was heat resistant, but was destroyed by reduction. Assays of CGF preparations revealed that they contained no detectable platelet-derived growth factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854719 TI - Characterization of covalent protein conjugates using solid-state 13C NMR spectroscopy. AB - Cross-polarization magic-angle spinning (CPMAS) 13C NMR spectroscopy has been used to characterize covalent conjugates of alachlor, an alpha-chloroacetamide hapten, with glutathione (GSH) and bovine serum albumin (BSA). The solid-state NMR method demonstrates definitively the covalent nature of these conjugates and can also be used to characterize the sites of hapten attachment to proteins. Three different sites of alachlor binding are observed in the BSA system. Accurate quantitation of the amount of hapten covalently bound to GSH and BSA is reported. The solid-state 13C NMR technique can easily be generalized to study other small molecule/protein conjugates and can be used to assist the development and refinement of synthetic methods needed for the successful formation of such protein alkylation products. PMID- 1854720 TI - Alternating zinc fingers in the human male associated protein ZFY: refinement of the NMR structure of an even finger by selective deuterium labeling and implications for DNA recognition. AB - ZFY, a male-associated Zn-finger protein encoded by the human Y chromosome, exhibits a distinctive two-finger repeat: whereas odd-numbered domains fit a general consensus, even-numbered domains exhibit systematic differences. Do these odd and even sequences encode structurally distinct surfaces for DNA recognition? As a first step toward answering this question, we have recently described the sequential 1H NMR assignment of a representative nonconsensus Zn finger (designated ZFY-6T) based on 2D NMR studies of a 30-residue peptide [Kochoyan, M., Havel, T.F., Nguyen, D.T., Dahl, C.E., Keutmann, H. T., & Weiss, M.A. (1991) Biochemistry 30, 3371-3386]. Initial structural modeling by distance geometry/simulated annealing (DG/SA) demonstrated that this peptide retained the N-terminal beta-hairpin and C-terminal alpha-helix (beta beta alpha motif) observed in consensus Zn fingers. However, the precision of this initial structure was limited by resonance overlap, which led to ambiguities in the assignment of key NOEs in the hydrophobic core. In this paper these ambiguities are resolved by selective deuterium labeling, enabling a refined structure to be calculated by DG/SA and restrained molecular dynamics. These calculations provide a detailed view of the hydrophobic core and protein surface, which are analyzed in reference to previously characterized Zn fingers. Variant (even) and consensus (odd) aromatic residues Y10 and F12, shown in an "aromatic swap" analogue to provide equivalent contributions to the hydrophobic core [Weiss, M.A., & Keutmann, H.T. (1990) Biochemistry 29, 9808-9813], nevertheless exhibit striking differences in packing interactions: Y10--but not F12--contributes to a contiguous region of the protein surface defined by putative specificity determining residues. Alternating surface architectures may have implications for the mechanism of DNA recognition by the ZFY two-finger repeat. PMID- 1854721 TI - Nucleotide positions responsible for the processivity of the reaction of exonuclease I with oligodeoxyribonucleotides. AB - The processive hydrolysis of single-stranded oligodeoxyribonucleotides by exonuclease I from Escherichia coli has been investigated. Oligodeoxyribonucleotides and their analogues, which contain either an abasic site or a methylphosphonate internucleotide linkage, were partially hydrolyzed by exonuclease I. The relative dissociation constant for the enzyme and each oligomeric product was calculated from the concentration of that oligomer found in solution and hence released by the enzyme before complete hydrolysis. The results have led to a characterization of the two oligodeoxyribonucleotide domains that bind to exonuclease I. The first domain, which begins at the reactive 3'-terminal phosphodiester and extends to the 7th nucleoside base, requires both phosphodiester monoanions and base residues for its interaction with the enzyme. The second domain includes phosphodiester monoanions in positions 9-13 from the 3'-terminus but does not require nucleoside bases. Methylphosphonate substitutions indicate that only two or three of these phosphodiesters, in variable positions, must remain anionic in order to obtain full enzyme binding. The residues between the two binding domains do not play a significant role in the enzyme-oligomer interaction. PMID- 1854722 TI - Regulation of extracellular matrix production by chemically synthesized subfragments of type I collagen carboxy propeptide. AB - The complete COOH-propeptide of human alpha 1(I) procollagen was chemically synthesized as a series of overlapping subfragments which were then tested for their effect on extracellular matrix protein production by subconfluent human lung fibroblasts (HFL-1). One peptide (R11; residues 197-241) stimulated production of both collagen and fibronectin by 6-8-fold while a second peptide with a partial overlap with R11 (R9; residues 182-216) enhanced collagen accumulation. The peptide R12 (residues 197-216), which has a sequence common to both R9 and R11, also stimulated collagen production, suggesting that this 20 residues peptide alone contains the required structure for activity. The other synthetic peptides, R1-R13, were inactive in their ability to alter collagen or fibronectin production. Consistent with previously published data, the COOH terminal peptide, R14, inhibited extracellular matrix production [Aycock, R.A., Raghow, R., Stricklin, G.P., Seyer, J.M., & Kang, A.H. (1986) J. Biol. Chem. 261, 14355-14360]. Both R9 and R11 preferentially stimulated production of collagen types I and III and fibronectin in dose-dependent manner. Elevated collagen and fibronectin production was evident at 4-h posttreatment, and maximal enhancement was seen at 8 h after exposure to peptides. Interestingly, subconfluent cultures of HFL-1 fibroblasts responded vigorously to the stimulatory action of R9 and R11 while confluent cells failed to show any response. Steady-state levels of messenger RNAs encoding type I procollagen and fibronectin were not measurably altered by treatment with R9 or R11, suggesting that the regulation of procollagens and fibronectin by these peptides involves posttranscriptional mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854723 TI - An in vitro novel mechanism of regulating the activity of pyruvate kinase M2 by thyroid hormone and fructose 1, 6-bisphosphate. AB - We have recently shown that the cytosolic thyroid hormone binding protein (p58 M2) in human epidermoid carcinoma A431 cells is a monomer of pyruvate kinase, subtype M2 (PKM2). To characterize further the molecular properties of p58-M2, we overexpressed p58-M2 in Escherichia coli and purified it to homogeneity. At 22 degrees C, the monomeric p58-M2, exhibited kinase activity with an apparent Vmax of 22 +/- 9 units/mg. The Km for adenosine diphosphate (ADP) and phosphoenolpyruvate (PEP) are 3.85 +/- 2.4 and 1.55 +/- 0.73 mM, respectively. Upon activation by fructose 1,6-bisphosphate (Fru-1,6-P2), Vmax and Km for ADP and PEP were changed to 490 +/- 27 units/mg and 0.63 +/- 0.09 and 0.13 +/- 0.01 mM, respectively. These results indicated that p58-M2 has intrinsic kinase activity. Analysis of the molecular size indicated that the activation of p58-M2, by Fru-1,6-P2 resulted in the association of the monomeric p58-M2 to the tetrameric PKM2. p58-M2 bound to 3,3',5-triiodo-L-thyronine (T3) (Ka = 1.7 x 10(7) M-1) and exhibited analogue specificity, whereas PKM2 did not bind thyroid hormone. The order of binding affinity was L-T3 greater than L-thyroxine greater than 3,3',5-triiodothyropropionic acid greater than 3'-isopropyl-3,5-triiodo-L thyronine greater than 3'5',3-triiodo-L-thyronine. Binding of T3 and its analogues resulted in the inhibition of the kinase activity of p58-M2. The order of kinase inhibitory activity and preventing its association to tetrameric PKM2 was parallel to that of binding activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854724 TI - Identification of cysteine-319 as the target amino acid of 8-[(4-bromo-2,3 dioxobutyl)thio]adenosine 5'-triphosphate in bovine liver glutamate dehydrogenase. AB - The affinity label 8-[(4-bromo-2,3-dioxobutyl)thio]adenosine 5'-triphosphate (8 BDB-TA-5'-TP) has been shown to react with bovine liver glutamate dehydrogenase in the region of the GTP-dependent NADH inhibitory site with incorporation of about 1 mol of reagent/mol of subunit [Ozturk, D. H., Safer, D., & Colman, R. F. (1990) Biochemistry 29, 7112-7118]. The modified enzyme was shown to contain only 5 free sulfhydryl groups upon 5,5'-dithiobis (2-nitrobenzoate) titration as compared with 6 in the unmodified enzyme. In the unmodified enzyme digested with trypsin, 6 cysteinyl peptides were detected by high-performance liquid chromatography upon treatment with iodo [3H]acetic acid. In contrast, only 5 (carboxymethyl)cysteinyl peptides were detected in 8-BDB-TA-5'-TP-modified enzyme. When carboxymethylated modified and unmodified enzymes were digested with thermolysin, 6 peptide sequences containing (carboxymethyl)cysteine were obtained in the unmodified enzyme, but only 5 were observed in the modified enzyme. The (carboxymethyl)cysteine which was absent in the modified enzyme was determined to be Cys-319, leading to the conclusion that 8-BDB-TA-5'-TP reacts with Cys-319, thereby preventing it from subsequent reaction with radioactive iodoacetate. It was previously reported that 6-[(4-bromo-2,3-dioxobutyl)thio]-6-deaminoadenosine 5'-diphosphate (6-BDB-TA-5'-DP) modifies Cys-319 in this enzyme [Batra, S. P., & Colman, R. F. (1986) Biochemistry 25, 3508-3515].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854725 TI - Effect of lactoperoxidase-catalyzed iodination on the Ca(2+)-dependent interactions of human C1s. Location of the iodination sites. AB - C-1s, one of the two serine proteases of C-1, the first component of complement, has the ability to mediate heterologous (C-1r-C-1s) as well as homologous (C-1s-C 1s) Ca(2+)-dependent interactions both involving the NH2-terminal alpha region of its A chain. Lactoperoxidase-catalyzed iodination of C-1s in its monomeric form was found to abolish its ability to form Ca(2+)-dependent homodimers, without impairing its ability to mediate C-1r-C-1s heteroassociation. C-1s iodinated in its dimeric form, in contrast, fully retained the ability to self-associate. With a view to identify the tyrosine residues iodinated in each case, C-1s was radioiodinated in its monomeric and dimeric forms, and comparative tryptic mapping was performed on the resulting 125I-labeled A chains. Most of the tyrosine residues either were not iodinated or were equivalently but not in the dimer. Conversely, Tyr-52 and Tyr-147 were iodinated only in the dimer. These results provide further evidence that the structural determinants of C-1s required for Ca2+ binding and Ca(2+)-dependent protein-protein interactions are contributed by both the NH2-terminal motif I (positions 1-110) and the epidermal growth factor like motif II (positions 111-159) of the alpha region. On the basis of available information, tentative models of the C-1s-C-1s and C-1r-C-1s Ca(2+) dependent interactions are proposed. PMID- 1854726 TI - Contributions of engineered surface salt bridges to the stability of T4 lysozyme determined by directed mutagenesis. AB - Six designed mutants of T4 lysozyme were created in an attempt to create putative salt bridges on the surface of the protein. The first three of the mutants, T115E (Thr 115 to Glu), Q123E, and N144E, were designed to introduce a new charged side chain close to one or more existing charged groups of the opposite sign on the surface of the protein. In each of these cases the putative electrostatic interactions introduced by the mutation include possible salt bridges between residues within consecutive turns of an alpha-helix. Effects of the mutations ranged from no change in stability to a 1.5 degrees C (0.5 kcal/mol) increase in melting temperature. In two cases, secondary (double) mutants were constructed as controls in which the charge partner was removed from the primary mutant structure. These controls proteins indicate that the contributions to stability from each of the engineered salt bridges is very small (about 0.1-0.25 kcal/mol in 0.15 M KCl). The structures of the three primary mutants were determined by X ray crystallography and shown to be essentially the same as the wild-type structure except at the site of the mutation. Although the introduced charges in the T115E and Q123E structures are within 3-5 A of their intended partner, the introduced side chains and their intended partners were observed to be quite mobile. It has been shown that the salt bridge between His 31 and Asp 70 in T4 lysozyme stabilizes the protein by 3-5 kcal/mol [Anderson, D. E., Becktel, W. J., & Dahlquist, F. W. (1990) Biochemistry 29, 2403-2408]. To test the effectiveness of His...Asp interactions in general, three additional double mutants, K60H/L13D, K83H/A112D, and S90H/Q122D, were created in order to introduce histidine aspartate charge pairs on the surface of the protein. Each of these mutants destabilizes the protein by 1-3 kcal/mol in 0.15 M KCl at pH values from 2 to 6.5. The X-ray crystallographic structure of the mutant K83H/A112D has been determined and shows that there are backbone conformational changes of 0.3-0.6 A extending over several residues. The introduction of the histidine and aspartate presumably introduces strain into the folded protein that destabilizes this variant. It is concluded that pairs of oppositely charged residues that are on the surface of a protein and have freedom to adopt different conformations do not tend to come together to form structurally localized salt bridges. Rather, such residues tend to remain mobile, interact weakly if at all, and do not contribute significantly to protein stability. It is argued that the entropic cost of localizing a pair of solvent-exposed charged groups on the surface of a protein largely offsets the interaction energy expected from the formation of a defined salt bridge. There are examples of strong salt bridges in proteins, but such interactions require that the folding of the protein provides the requisite driving energy to hold the interacting partners in the correct rigid alignment. PMID- 1854727 TI - Average membrane penetration depth of tryptophan residues of the nicotinic acetylcholine receptor by the parallax method. AB - The membrane penetration depths of tryptophan residues in the nicotinic acetylcholine receptor from Torpedo californica have been analyzed in reconstituted membranes containing purified receptor and defined lipids. Dioleoylphosphatidylcholine and three spin-labeled phosphatidylcholines with the nitroxide group at three different positions on the fatty acyl chain were used for reconstitution of the receptor. The spin-labeled phospholipids serve as quenchers of tryptophan fluorescence. Differential quenching of the intrinsic fluorescence of the acetylcholine receptor by the spin-labeled phospholipids has been utilized to analyze the average membrane penetration depth of tryptophans by the parallax method [Chattopadhyay, A., & London, E. (1987) Biochemistry 26, 39 45]. Analyses of the quenching data indicate that the tryptophan residues on the average are at a shallow location (10.1 A from the center of the bilayer) in the membrane. In addition, the generally low levels of quenching imply that the majority of tryptophan residues are located in the putative extramembranous region of the receptor. These results are consistent with several proposed models for the tertiary structure of the acetylcholine receptor and are relevant to ongoing analyses of the overall conformation and orientation of the acetylcholine receptor in the membrane. PMID- 1854728 TI - Effects of the crystalline structure of purple membrane on the kinetics and energetics of the bacteriorhodopsin photocycle. AB - Time-resolved difference spectra were measured for Triton X-100 solubilized bacteriorhodopsin monomers between 100 ns and 100 ms after photoexcitation. The results are consistent with the general scheme K in equilibrium L in equilibrium M1 in equilibrium M2 in equilibrium N in equilibrium O----BR proposed previously for purple membranes [Varo, G., & Lanyi, J.K. (1990) Biochemistry 29, 2241-2250]. The rate constants which involve proton release or uptake, i.e., kLM1, kNO, and kON, were significantly higher in the monomeric protein than in purple membrane; the other steps were less affected. Analysis of the temperature dependencies of the rate constants between 5 and 30 degrees C yielded the enthalpies and entropies of activation for all steps except the two absent back-reactions. Comparison of these with data for purple membranes [Varo, G., & Lanyi, J.K. (1991) Biochemistry 30, 5016-5022] shows that the crystalline structure affects the energetics of the photocycle. In bacteriorhodopsin immobilized by the lattice of the purple membrane, the entropy changes leading to all transition states are more positive. Thus, the forward reactions proceed with less conformational hindrance. However, the thermal (enthalpic) barriers are higher. These effects are particularly pronounced for the M1----M2 and O----BR reactions. Large changes of the enthalpy and entropy levels of intermediates in the M2----BR reaction segment, but not in the K----M1 segment, upon solubilization of the protein are consistent with our earlier proposal that major protein conformational changes occur in the photocycle and they begin with the M1----M2 reaction. PMID- 1854729 TI - How membrane chain-melting phase-transition temperature is affected by the lipid chain asymmetry and degree of unsaturation: an effective chain-length model. AB - Hydrocarbon effects on the lipid chain-melting phase-transition temperature are analyzed. The membrane fluidization temperature is shown to increase with the effective chain length, which is proportional to the thickness of the well-packed hydrocarbon region. The latter, as a rule, increases with the length of the longest ordered and aligned segment on each chain. This conclusion is independent of the cause for the reduced chain packing in membrane interior: chain unsaturation (which effectively decouples the two hydrocarbon segments disjoined by a double bond) or chain asymmetry (which causes the terminal hydrocarbon segments to lose close contact) both affect the bilayer chain-melting phase transition temperature comparably on the effective chain-length scale. Thermodynamic consequences of the trans unsaturation are approximately 50% smaller than the effects of the double bonds in the cis conformation, owing to the smaller membrane perturbation by the former double bonds. A simple quantitative model is introduced for the analysis of the phospholipid chain melting phase behavior. This new model permits quantitative predictions of the chain-melting transition temperature solely on the basis of the known lipid chemical composition. It also explains lipid sensitivity to the hydrocarbon type and attachment. The model agreement with the experimental data is usually better than to within 99% and thus comparable to experimental scatter, even when only a few or no adjustable parameters are used. The membrane fluidization temperature is calculated for a number of potentially interesting, also as yet unexplored, phospholipids, and the biological significance of the effective chain-length concept is discussed. PMID- 1854730 TI - Thermotropic and mixing behavior of mixed-chain phosphatidylcholines with molecular weights identical with that of L-alpha-dipalmitoylphosphatidylcholine. AB - The thermotropic phase behavior of 10 mixed-chain phosphatidylcholines, in excess water, has been examined and compared with that of identical-chain C(16):C(16)PC by using high-resolution differential scanning calorimetry (DSC). The molecular weights (MW) of these 11 molecular species are the same, but their delta C/CL values, or the normalized chain length differences, vary considerably, ranging from 0.035 to 0.540. The thermodynamic parameters (Tm, delta H, and delta S) associated with the main phase transitions for these lipid dispersions exhibit biphasic V-shaped curves, when plotted against delta C/CL. Similar characteristic curves have been reported previously for aqueous dispersions of mixed-chain phosphatidylcholines with MW identical with that of C(17):C(17)PC [Lin et al. (1990) Biochemistry 29, 7063-7072]. The initial decrease in Tm (delta H or delta S) with increasing values of delta C/CL is attributed to the progressive increase in the magnitude of the chain-terminal perturbations on the conformational statistics of the adjacent hydrocarbon chains and hence the lateral chain-chain interactions of these mixed-chain phosphatidylcholines in the gel-state bilayer. At delta C/CL approximately equal to 0.42, the chain-end perturbation is presumably at its maximum; beyond this point, the highly asymmetric phosphatidylcholines are proposed to pack, at T less than Tm, into the mixed interdigitated bilayer. In this new packing mode, the methyl ends of the longer acyl chains are relocated at the interfaces between the hydrocarbon core of the bilayer and the aqueous medium. This disposition of the bulky chain ends releases a certain degree of chain-chain packing disorders, leading to an increase in Tm (delta H or delta S) with increasing delta C/CL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854731 TI - Molecular organization and stability of hydrated dispersions of headgroup modified phosphatidylethanolamine analogues. AB - Measurements of the thermotropic behavior of various headgroup-modified analogues of 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE) and of the ion-triggered destabilization of unilamellar vesicles containing these species have been correlated with X-ray diffraction measurements of the organization of hydrated dispersions of these analogues in the absence and presence of dodecane. The hexagonal II lattice repeat dimension -dhex for dodecane-supplemented dispersions, which reflects the optimal or "spontaneous" radius of surface curvature of the phospholipid component, is increased relative to POPE for most analogues with N-alkyl substitutents or increased amino-to-phosphate group separations. Interestingly, however, POPE analogues that are alkylated on C-1 or C-2 of the ethaolamine group show smaller -dhex values (and hence smaller spontaneous radii of surface curvature) than does POPE itself, despite the greater steric bulk of their headgroups. The lamellar-to-hexagonal II transition temperatures of the various POPE analogues and their abilities to promote contact dependent vesicle destabilization both show strong correlations with the analogues' measured -dhex values (and hence with their spontaneous radii of curvature). The uniformity of these correlations over a wide range of headgroup structures strongly supports, and may help to refine, recent theories which postulate that the spontaneous surface curvature of a lipid or lipid mixture is a central, quantitative determinant of its tendency to adopt nonlamellar phases and to undergo contact-dependent bilayer destabilization. PMID- 1854732 TI - Synthesis and characterization of a heterobifunctional mercurial cross-linking agent: incorporation into cobratoxin and interaction with the nicotinic acetylcholine receptor. AB - The heterobifunctional organomercurial reagents 3-(acetoxymercurio)- and 3 (chloromercurio)-5-nitrosalicylaldehyde were prepared, characterized in model studies, and used to probe the interaction between cobratoxin, purified from the venom of the Thailand cobra (Naja naja siamensis), and the affinity-purified nicotinic acetylcholine receptor (AcChR) from Torpedo california electroplax. These reagents may also be useful in introducing chemically well-defined heavy metal atoms into proteins containing no reactive thiols. Model reagent adducts were prepared in situ by reductive amination with N-butylamine and N alpha acetyllysine-N-methylamide. The nitrophenolic pKaS of the amine adducts were similar to those of the aldehyde reagents through reduced by 1.3-1.5 units when compared with the hydroxylmethyl reduction product. Reaction of either mercuriosalicylaldehyde with cobratoxin led to a single major modification product incorporating 1 mol of the reagent into cobratoxin at Lys 23. The Lys 23 modified toxin had a reduced binding affinity for the AcChR over that of the native toxin (Kd 2.75 nM cf. 0.3 nM). Reduction of the purified AcChR with 1 mM dithiothreitol (DTT) followed by removal of excess thiol led to cross-linking reactions with the Lys 23 modified cobratoxin to both the alpha and beta subunits of the AcChR complex. Reaction of DTT-treated AcChR with N-ethylmaleimide (NEM) blocked cross-linking, while treatment of the initially cross-linked toxin-AcChR complex with mercaptoethanol leads to reversal of cross-linking. These observations strongly support cross-linking mediated by the formation of a mercury-sulfur bond and further lend support the identity of the respective interacting sites in AcChR and toxin. PMID- 1854733 TI - Calcium-induced sensitization of the central helix of calmodulin to proteolysis. AB - The rate of proteolysis of trypsin-sensitive bonds was used to examine the nature of the structural changes accompanying Ca2+ and Mg2+ binding to calmodulin. In the Ca(2+)-free form, the rates of proteolysis at Arg-106 and Arg-37 are rapid (greater than 300 and 28 nmol min-1 mL-1, respectively), the bonds at Arg-74, Lys 75, and Lys-77, in the central helix, are cleaved more slowly (10 nmol min-1 mL 1), and a lag in the cleavage at the remaining bonds (Lys-13, Lys-30, Arg-86, Arg 90, and Arg-126) suggests that they are not cleaved in the native protein. High concentrations of Ca2+, but not Mg2+, almost completely abolish proteolysis at Arg-106 and drastically reduce the rate of cleavage at Arg-37. Both Ca2+ and Mg2+ exert a moderate protective effect on the proteolysis of the central helix. These results suggest that the F-helix of domains III and, to a lesser extent, the F helix of domain I are somewhat flexible in the Ca(2+)-free form and are stabilized by Ca2+. Whereas full occupancy of the four Ca(2+)-binding sites produces little change in the susceptibility of the central helix to proteolytic attack, binding of two Ca2+ produces a 10-fold enhancement of the rate of proteolysis in this part of the molecule. We propose that at intermediate Ca2+ levels the flexibility of the central helix of calmodulin is greatly increased, resulting in the transient formation of intermediates which have not been detected by spectroscopic techniques but are trapped by the irreversible action of trypsin. PMID- 1854734 TI - Variations of electrostatic interactions in myoglobin probed by UVRR spectroscopy. Effect of iron ligand and pH on tryptophan and tyrosine vibrations. AB - The present work investigates the variations of electrostatic interactions within the myoglobin molecule associated with azide heme binding and pH variations. Far ultraviolet (223 nm) resonance Raman spectroscopy of the tryptophan and tyrosine residues, along with acid-base titration measurements, have been used to monitor variations in the protein matrix. With previously determined mode assignments, it is shown that the Trp and Tyr residues of the globin moiety are influenced by the charge spatial distribution. Upon ligand binding or under various pH conditions, the polar interactions inside the protein appear to be modulated by the electric field generated by the charge array. It is concluded that the binding site properties of myoglobin can be modulated by the charge spatial distribution within the protein, even in the absence of measurable conformational changes of the bulk. PMID- 1854735 TI - Experimental resolution of cooperative free energies for the ten ligation species of cobalt(II)/iron(II)-CO hemoglobin. AB - Cooperative free energies have been determined for the 10 ligation species of human hemoglobin in the Co(II)/Fe(II)-CO system. In this system, subunits containing unligated cobaltous hemes coexist in the same tetramer with naturally occurring ferrous hemes that are ligated with carbon monoxide. Tetramers comprising the 10 structurally unique combinations of ligated and unligated subunits were characterized in terms of their dimer-tetramer assembly free energies. By use of the thermodynamic linkage between assembly and ligation, the experimentally resolved values were used to obtain the corresponding cooperative free energies (i.e., the differences between actual free energies of ligation and the summed contributions of intrinsic values). The results obtained are in general accord with previous findings on this same system (Imai et al., 1980). The present study extends this earlier work by resolving the cooperative properties of each configurational isomer of the doubly ligated tetramers. The 10 ligation species were found to distribute into 5 discrete cooperative free energy levels according to a combinatorial code which includes, as a special case, the code found previously with cyanomethemoglobin and manganese-substituted hemoglobin (Smith et al., 1987; Daugherty et al., 1991). This distribution exhibits additional characteristics found in the oxygenation of normal ferrous hemoglobin including the quaternary enhancement effect (Mills & Ackers, 1979a,b). These results, and those of the following paper (Doyle et al., 1991), strongly support the premise that a common set of qualitative rules governs the cooperative interactions in hemoglobin irrespective of PMID- 1854736 TI - Linkage between cooperative oxygenation and subunit assembly of cobaltous human hemoglobin. AB - The thermodynamic linkage between cooperative oxygenation and dimer-tetramer subunit assembly has been determined for cobaltous human hemoglobin in which iron(II) protoporphyrin IX is replaced by cobalt(II) protoporphyrin IX. The equilibrium parameters of the linkage system were determined by global nonlinear least-squares regression of oxygenation isotherms measured over a range of hemoglobin concentrations together with the deoxygenated dimer-tetramer assembly free energy determined independently from forward and reverse reaction rates. The total cooperative free energy of tetrameric cobalt hemoglobin (over all four binding steps) is found to be 1.84 (+/- 0.13) kcal, compared with the native ferrous hemoglobin value of 6.30 (+/- 0.14) kcal. Detailed investigation of stepwise cooperativity effects shows the following: (1) The largest change occurs at the first ligation step and is determined on model-independent grounds by knowledge of the intermediate subunit assembly free energies. (2) Cooperativity in the shape of the tetrameric isotherm occurs mainly during the middle two steps and is concomitant with the release of quaternary constraints. (3) Although evaluation of the pure tetrameric isotherm portrays identical binding affinity between the last two steps, this apparent noncooperativity is the result of a "hidden" oxygen affinity enhancement at the last step of 0.48 (+/- 0.12) kcal. This quaternary enhancement energy is revealed by the difference in subunit assembly free energies of the triply and fully ligated species and is manifested visually by the oxygenation isotherms at high versus low hemoglobin concentration. (4) Cobaltous hemoglobin dimers exhibit apparent anticooperativity of 0.49 (+/- 0.16) kcal (presumed to arise from heterogeneity of subunit affinities).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854737 TI - Interfacial catalysis by phospholipase A2: determination of the interfacial kinetic rate constants. AB - Hydrolysis of vesicles of 1,2-dimyristoyl-sn-glycero-3-phosphomethanol (DMPM) by pig pancreatic phospholipase A2 (PLA2) occurs in a highly processive "scooting" mode, and the rate is comparable to or exceeds the rates observed with detergent dispersed mixed micelles under optimal conditions. A complete kinetic description of the steady-state time course of the hydrolysis is developed. The analysis covers the whole Michaelis-Menten space: it emphasizes the key features of interfacial catalysis by a detailed theoretical analysis, describes the experimental protocols to determine the values of the kinetic and equilibrium constants for interfacial catalysis, and provides an interpretation of the effect of calcium, substrate, products, apparent activators, and competitive inhibitors on the reaction progress curve by a single set of rate and equilibrium parameters. In this paper, the integrated reaction progress curve was rigorously interpreted in terms of a minimal model involving the Michaelis-Menten reaction sequence in the interface: E* + S in equilibrium E*S----E*P in equilibrium E* + P, and most of the individual rate and equilibrium constants for the catalytic cycle were determined. This rigorous description of interfacial catalysis was made experimentally possible by examining the action of PLA2 in the scooting mode under conditions of at most one enzyme per vesicle, where it hydrolyzed all of the substrate in the outer monolayer of vesicles without leaving the surface. Other experimentally verified constraints for this analysis include the following: all enzyme was bound to vesicles; the integrity of vesicles was maintained during the course of hydrolysis; and the substrate, enzyme, and products did not exchange between vesicles nor did they exchange across the bilayer. The mechanistic significance of the rate constants is discussed in the accompanying papers. PMID- 1854738 TI - Interfacial catalysis by phospholipase A2: evaluation of the interfacial rate constants by steady-state isotope effect studies. AB - The kinetics of hydrolysis of phospholipid vesicles by phospholipase A2 (PLA2) in the scooting mode can be described by the Michaelis-Menten formalism for the action of the enzyme in the interface (E*). E* + S in equilibrium E*S in equilibrium E*P in equilibrium E* + Products The values of the interfacial rate constants cannot be obtained by classical methods because the concentration of the substrate within the lipid bilayer is not easily manipulated. In the present study, carbonyl-carbon heavy atom isotope effects for the hydrolysis of phospholipids have been measured in both vesicles and in mixed micelles in which the phospholipid was present in the nonionic detergent Triton X-100. A large [14C]carbonyl carbon isotope effect of 1.12 +/- 0.02 was measured for the cobra venom PLA2-catalyzed hydrolysis of dipalmitoylphosphatidylcholine in Triton X 100. In contrast, no isotope effect (1.01 +/- 0.01) was measured for the action of the porcine pancreatic and cobra venom enzymes on vesicles of dimyristoylphosphatidylmethanol in the scooting mode. In a second experiment, the hydrolysis of vesicles was carried out in oxygen-18 enriched water. Analysis of the released fatty acid product by mass spectrometry showed that it contained only a single oxygen-18. All of these results were used to estimate both the forward and reverse commitments to catalysis. The lack of doubly labeled fatty acid demonstrated that the product is released from the E*P complex faster than the reverse of the esterolysis step. The small isotope effect in vesicles demonstrated that the E*S complex goes on to products faster than substrate is released from the enzyme. The relevance of these results to an understanding of substrate specificity and inhibition of PLA2 is discussed. In addition, the conditions placed on the values of the rate constants obtained in the present study together with results obtained in the other studies described in this series of papers have led to the evaluation of most of the interfacial rate constants for the hydrolysis of phospholipid vesicles by PLA2. PMID- 1854739 TI - Interfacial catalysis by phospholipase A2: dissociation constants for calcium, substrate, products, and competitive inhibitors. AB - Interpretation of the kinetics of interfacial catalysis in the scooting mode as developed in the first paper of this series [Berg et al. (1991) Biochemistry 30 (first paper of six in this issue)], was based on the binding equilibrium for a ligand to the catalytic site of phospholipase A2. In this paper, we describe direct methods to determine the value of the Michaelis-Menten constant (KMS) for the substrate, as well as the equilibrium dissociation constants for ligands (KL) such as inhibitors (KI), products (KP), calcium (KCa), and substrate analogues (KS) bound to the catalytic site of phospholipase A2 at the interface. The KL values were obtained by monitoring the susceptibility to alkylation of His-48 at the catalytic site of pig pancreatic PLA2 bound to micellar dispersions of the neutral diluent 2-hexadecyl-sn-glycero-3-phosphocholine. The binding of the enzyme to dispersions of this amphiphile alone had little effect on the inactivation rate. The half-time for inactivation of the enzyme bound to micelles of the neutral diluent depended not only on the nature of the alkylating agent but also on the structure and the mole fraction of other ligands at the interface. The KL values for ligands obtained from the protection studies were in excellent accord with those obtained by monitoring the activation or inhibition of hydrolysis of vesicles of 1,2-dimyristoyl-sn-glycerophosphomethanol. Since only calcium, competitive inhibitors, and substrate analogues protected phospholipase A2 from alkylation, this protocol offered an unequivocal method to discern active-site-directed inhibitors from nonspecific inhibitors of PLA2, such as local anesthetics, phenothiazines, mepacrine, peptides related to lipocortin, 7,7-dimethyleicosadienoic acid, quinacrine, and aristolochic acid, all of which did not have any effect on the kinetics of alkylation nor did they inhibit the catalysis in the scooting mode. PMID- 1854740 TI - Interfacial catalysis by phospholipase A2: substrate specificity in vesicles. AB - The binding equilibrium of phospholipase A2 (PLA2) to the substrate interface influences many aspects of the overall kinetics of interfacial catalysis by this enzyme. For example, the interpretation of kinetic data on substrate specificity was difficult when there was a significant kinetic contribution from the interfacial binding step to the steady-state catalytic turnover. This problem was commonly encountered with vesicles of zwitterionic phospholipids, where the binding of PLA2 to the interface was relatively poor. The action of PLA2 on phosphatidylcholine (PC) vesicles containing a small amount of anionic phospholipid, such as phosphatidic acid (PA), was studied. It was shown that the hydrolysis of these mixed lipid vesicles occurs in the scooting mode in which the enzyme remains tightly bound to the interface and only the substrate molecules present on the outer monolayer of the target vesicle became hydrolyzed Thus the phenomenon of scooting mode hydrolysis was not restricted to the action of PLA2 on vesicles of pure anionic phospholipids, but it was also observed with vesicles of zwitterionic lipids as long as a critical amount of anionic compound was present. Under such conditions, the initial rate of hydrolysis of PC in the mixed PC/PA vesicles was enhanced more than 50-fold. Binding studies of PLA2 to vesicles and kinetic studies in the scooting mode demonstrated that the enhancement of PC hydrolysis in the PC/PA covesicles was due to the much higher affinity of the enzyme toward covesicles compared to vesicles of pure PC phospholipids. A novel and technically simple protocol for accurate determination of the substrate specificity of PLA2 at the interface was also developed by using a double-radiolabel approach. Here, the action of PLA2 in the scooting mode was studied on vesicles of the anionic phospholipid 1,2-dimyristoyl-sn-glycero-3 phosphomethanol that contained small amounts of 3H- and 14C-labeled phospholipids. From an analysis of the 3H and 14C radioactivity in the released fatty acid products, the ratio of substrate specificity constants (kcat/KMS) was obtained for any pair of radiolabeled substrates. These studies showed that the PLA2s from pig pancreas and Naja naja naja venom did not discriminate between phosphatidylcholine and phosphatidylethanolamine phospholipids or between phospholipids with saturated versus unsaturated acyl chains and that the pig enzyme had a slight preference for anionic phospholipids (2-3-fold). The described protocol provided an accurate measure of the substrate specificity of PLA2 without complications arising from the differences in binding affinities of the enzyme to vesicles composed of pure phospholipids. PMID- 1854741 TI - Interfacial catalysis by phospholipase A2: monomeric enzyme is fully catalytically active at the bilayer interface. AB - Interfacial catalysis in the scooting mode by phospholipase A2 (PLA2) from pancreas and venoms (18 different preparations) was examined on vesicles of 1,2 dimyristoyl-sn-glycero-3-phosphomethanol under the conditions where the rates of transbilayer and intervesicle exchanges of the enzyme, substrate, and the products of hydrolysis were negligible on the time scale (less than 30 min) on which all the substrate molecules on the outer monolayer of the target vesicles were hydrolyzed. The reaction progress curves for all PLA2s exhibited no latency period (less than 3 s). When the vesicle to PLA2 ratio in the reaction mixture was high so that according to the Poissonian distribution model at most one enzyme was bound to a vesicle, the extent of hydrolysis increased linearly with the amount of enzyme in the reaction mixture. However, the extent of hydrolysis per enzyme, NS, remained the same for all PLA2s, and it corresponded to the size of the target vesicles determined by independent methods. Similarly, the initial rate of hydrolysis increased linearly with the enzyme concentration, and the slope of the log-log plot was one under the conditions of one or more enzyme per vesicle. Such observations showed that monomeric PLA2 is fully catalytically active at the interface. This conclusion was supported by the absence of intermolecular resonance energy transfer from tryptophan-3 donor in the native PLA2 to the anthraniloyl acceptor in An87-PLA2, the catalytically active derivative of PLA2 with an anthraniloyl fluorophore on lysine 87. In this system, intermolecular resonance energy transfer was seen only when the donor-acceptor molecules were "crowded" at a high surface density with a relatively low lipid to protein mole ratio. On the basis of these results, it was concluded that secretory PLA2s from venoms and pancreas are fully catalytically active as monomers. Additional studies reported here showed that acylation of PLA2 was not necessary for catalysis or binding to the interface and that the binding of the substrate to the active site of PLA2 was not necessary for the binding of the enzyme to the interface. PMID- 1854742 TI - Interfacial catalysis by phospholipase A2: activation by substrate replenishment. AB - Polymyxin B (Px), a cyclic cationic peptide, was shown to act as a potent activator of interfacial catalysis by phospholipase A2 (PLA2) acting on dimyristoylphosphatidylmethanol vesicles in the scooting mode. A 7-fold increase in the initial enzymatic velocity was seen with the pig pancreatic PLA2 in the presence of 1 microM Px. Initial experiments including the dependency of the degree of activation by Px on the source of the PLA2 suggested that Px bound to a cationic binding site on the enzyme. However, numerous additional observations led to the conclusion that activation by Px was due to its effects on the substrate interface. For example, the activation by Px was only seen when the PLA2 acted on small vesicles rather than larger ones, and all of the available substrate was eventually hydrolyzed in the presence of a small mole fraction of Px. Px did not promote the intervesicle exchange of PLA2, and it did not alter the binding of the evidence led to the conclusion that Px activated interfacial catalysis by promoting the replenishment of substrate in the enzyme-containing vesicles. When PLA2 was acting on small vesicles in the scooting mode, the observed initial velocity was lower than that measured with large vesicles because the surface concentration of substrate decreased relatively rapidly in the small vesicles. Px promoted the transfer of phospholipids between the vesicles and functioned as an activator by keeping the mole fraction of substrate in the enzyme-containing vesicles close to 1. This effect of Px was consistent with the ability of polycationic peptides to induce the intervesicle mixing of anionic phospholipids in vesicles [Bondeson, J., & Sundler, R. (1990) Biochim. Biophys. Act 1026, 186-194]. Activation by substrate replenishment was quantitatively predicted by the theory of interfacial catalysis on vesicles in the scooting mode. The role of substrate replenishment in the kinetics of interfacial catalysis in phospholipid micelles was discussed. Finally, the protocols developed in this paper were outlined in view of their utility in the analysis of activators of interfacial catalysis. PMID- 1854743 TI - Three-dimensional structure of echistatin, the smallest active RGD protein. AB - Echistatin is a 49 amino acid protein isolated from the venom of a viper (Echis carinatus) and is one of the smallest natural adhesive ligands that interacts with integrin-type receptors through an Arg-Gly-Asp (RGD) sequence. The structure of echistatin in aqueous solution has been determined by nuclear magnetic resonance spectroscopy. Nuclear Overhauser spectra yielded 490 interatomic distance constraints, which were used in distance geometry calculations. The chain is shown to fold in a series of irregular loops to form a rigid core stabilized by four cystine cross-links. From this core an irregular hairpin and the C-terminus protrude. The core and the hairpin are further stabilized by a network of hydrogen bonds. The RGD sequence is located in a mobile loop at the tip of the hairpin. The mobility and its significance for activity are discussed. PMID- 1854744 TI - Investigations of optical line shapes and kinetic hole burning in myoglobin. AB - We present the results of an extensive investigation of the optical line shapes of deoxymyoglobin (Mb), the ligand-bound form (MbCO), and the low-temperature photoproduct (Mb*). The thermal properties and the pH dependence of the Soret band and the near infrared band III (approximately 760 nm) are analyzed, taking into account the underlying vibrational properties of the absorption bands. The strong temperature dependence associated with the Soret band of MbCO and band III of Mb indicates significant coupling to low-frequency modes that may not be directly observed in the resonance Raman spectra. On the basis of analogous line shape studies in a variety of heme systems, we assign the low-frequency coupling in MbCO to torsional motions of the CO molecule. The low-frequency mode coupled to band III (approximately 70 cm-1) is found to lie quite close to the value for the heme-doming motion (approximately 50 cm-1) calculated by using the kinetically determined value of the force constant (17 N/m). Significant inhomogeneous broadening in the Soret region of Mb and Mb* is found to be due to a "nonkinetic" coordinate that we associate with the orientation of the proximal histidine. A "kinetic" coordinate, associated with the equilibrium displacement of the iron atom from the porphyrin plane (a) is found to contribute to the inhomogeneous broadening of both the Soret band and band III. The relaxation of the heme as the system evolves from from Mb* to Mb is followed optically as a function of temperature, and a sharp transition temperature is found at 185 K. The blue shifts of the Soret band and band III as Mb* evolves to Mb are found to be nearly identical (delta v*ABS approximately 140 cm-1) and attributed to changes in the mean value of a between Mb* (a*0) and Mb (a0 = 0.45 A). A simple quadratic model for the coordinate coupling that simultaneously accounts for the observed shift, delta v*ABS, the low-temperature kinetics and the kinetic hole burning predicts a*0 = 0.2 +/- 0.05 A and EA = 16 +/- 2 kJ/mol for the room temperature Arrhenius barrier height at the heme. A simple quantitative method for the analysis of kinetic hole-burning experiments is also developed and applied to recent studies involving quaternary and subunit-specific hemoglobin structures. PMID- 1854745 TI - Sequence-specific 1H NMR assignments, secondary structure, and location of the calcium binding site in the first epidermal growth factor like domain of blood coagulation factor IX. AB - Factor IX is a blood clotting protein that contains three regions, including a gamma-carboxyglutamic acid (Gla) domain, two tandemly connected epidermal growth factor like (EGF-like) domains, and a serine protease region. The protein exhibits a high-affinity calcium binding site in the first EGF-like domain, in addition to calcium binding in the Gla domain. The first EGF-like domain, factor IX (45-87), has been synthesized. Sequence-specific resonance assignment of the peptide has been made by using 2D NMR techniques, and its secondary structure has been determined. The protein is found to have two antiparallel beta-sheets, and preliminary distance geometry calculations indicate that the protein has two domains, separated by Trp28, with the overall structure being similar to that of EGF. An NMR investigation of the calcium-bound first EGF-like domain indicates the presence and location of a calcium binding site involving residues on both strands of one of the beta-sheets as well as the N-terminal region of the peptide. These results suggest that calcium binding in the first EGF-like domain could induce long-range (possibly interdomain) conformational changes in factor IX, rather than causing structural alterations in the EGF-like domain itself. PMID- 1854746 TI - Conformation of an enzyme-bound substrate of staphylococcal nuclease as determined by NMR. AB - The dinucleoside phosphodiester dTdA is a slow substrate of staphylococcal nuclease (kcat = 3.8 X 10(-3) s-1) that forms binary E-S and ternary E-M-S complexes with Ca2+, Mn2+, Co2+, and La3+. The enzyme enhances the paramagnetic effects of Co2+ on 1/T1 and 1/T2 of the phosphorus and on 1/T1 of six proton resonances of dTdA, and these effects are abolished by binding of the competitive inhibitor 3',5'-pdTp. From paramagnetic effects of Co2+ on 1/T2 of phosphorus, koff of dTdA from the ternary E-Co(2+)-dTdA complex is greater than or equal to 4.8 X 10(4) s-1 and kon greater than or equal to 1.4 X 10(6) M-1 s-1, indicating the 1/T1 values to be in fast exchange. From paramagnetic effects of enzyme-bound Co2+ on 1/T1 of phosphorus and protons, with use of a correlation time of 1.6 ps on the basis of 1/T1 values at 250 and 600 MHz, 7 metal-nucleus distances and 9 lower-limit metal-nucleus distances are calculated. The long Co2+ to 31P distance of 4.1 +/- 0.9 A, which is intermediate between that expected for direct phosphoryl coordination (3.31 +/- 0.02 A) and a second sphere complex with an intervening water ligand (4.75 +/- 0.02 A), suggests either a distorted inner sphere complex or the rapid averaging of 18% inner sphere and 82% second sphere complexes and may explain the reduced catalytic activity with small dinucleotide substrates. Seventeen interproton distances and 108 lower limit interproton distances in dTdA in the ternary E-La(3+)-dTdA complex were determined by NOESY spectra at 50-, 100-, and 200-ms mixing times. While metal-substrate and interproton distances alone did not yield a unique structure, the combination of both sets of distances yielded a very narrow range of conformations for enzyme bound dTdA, which was highly extended, with no base stacking, with high-anti glycosidic torsional angles for dT (64 degrees less than or equal to chi less than or equal to 73 degrees) and dA (66 degrees less than or equal to chi less than or equal to 68 degrees) and predominantly C-2'-endo sugar puckers for both nucleosides. Although the individual nucleosides are like those of B-DNA, their unstacked conformation, which is inappropriate for base pairing, as well as the conformational angles alpha and gamma of dA and zeta of dT, rule out B DNA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1854747 TI - Substrate-decreased modification by diethyl pyrocarbonate of two histidines in isocitrate lyase from Escherichia coli. AB - The inactivation of tetrameric 188-kDa isocitrate lyase from Escherichia coli at pH 6.8 (37 degrees C) by diethyl pyrocarbonate, exhibiting saturation kinetics, is accompanied by modification of histidine residues 266 and 306. Substrates isocitrate, glyoxylate, or glyoxylate plus succinate protect the enzyme from inactivation, but succinate alone does not. Removal of the carbethoxy groups from inactivated enzyme by treatment with hydroxylamine restores activity of isocitrate lyase. The present results suggest that the group-specific modifying reagent diethyl pyrocarbonate may be generally useful in determining the position of active site histidine residues in enzymes. PMID- 1854748 TI - Thyroid hormone dependent pituitary tumor cell growth in serum-free chemically defined culture. A new regulatory role for apotransferrin. AB - Thyroid hormone dependent GH1 rat pituitary tumor cell growth in serum-free chemically defined medium required a serum-derived mediator (i.e., thyromedin) which was identified as transferrin [Sirbasku, D.A., Stewart, B.H., Pakala, R., Eby, J.E., Sato, H., & Roscoe, J.M. (1990) Biochemistry 30, 295-304]. The transferrin isolated was consistent with the equine R or D variants and was biologically active only as apotransferrin (apoTf). To determine if other variants of horse transferrin also were thyromedins, a purification was developed which yielded seven separate forms. Initially, only four of these had activity when assayed in standard "iron salts containing" medium (ED50 values of 290-1160 nM). To further assess activity, the iron contents of all seven were altered either by saturation with ferric ammonium citrate or by citrate/acid depletion of the metal ion. Thereafter, potencies were compared in "iron salts containing" and "iron salts reduced" media. All seven variants proved to be active as apoTf. Bioassays in which apoTf was maximized showed ED50 values of 2.1-3.8 nM. Conversely, assays in which thyromedins were converted to Tf.2Fe showed no activity. Previously, the only known physiological function of apoTf was that of a carrier/detoxifier of iron; this study indicates a new role in hormone dependent pituitary cell growth. PMID- 1854749 TI - Binding sites for alpha-bungarotoxin and the noncompetitive inhibitor phencyclidine on a synthetic peptide comprising residues 172-227 of the alpha subunit of the nicotinic acetylcholine receptor. AB - The binding of the competitive antagonist alpha-bungarotoxin (alpha-Btx) and the noncompetitive inhibitor phencyclidine (PCP) to a synthetic peptide comprising residues 172-227 of the alpha-subunit of the Torpedo acetylcholine receptor has been characterized. 125I-alpha-Btx bound to the 172-227 peptide in a solid-phase assay and was competed by alpha-Btx (IC50 = 5.0 x 10(-8) M), d-tubocurarine (IC50 = 5.9 X 10(-5)M), and NaCl (IC50 = 7.9 x 10(-2)M). In the presence of 0.02% sodium dodecyl sulfate, 125I-alpha-Btx bound to the 56-residue peptide with a KD of 3.5 nM, as determined by equilibrium saturation binding studies. Because alpha Btx binds to a peptide comprising residues 173-204 with the same affinity and does not bind to a peptide comprising residues 205-227, the competitive antagonist and hence agonist binding site lies between residues 173 and 204. After photoaffinity labeling, [3H]PCP was bound to the 172-227 peptide. [3H]PCP binding was inhibited by chlorpromazine (IC50 = 6.3 x 10(-5)M), tetracaine (IC50 = 4.2 x 10(-6)M), and dibucaine (IC50 = 2.7 x 10(-4)M). Equilibrium saturation binding studies in the presence of 0.02% sodium dodecyl sulfate showed that [3H]PCP bound at two sites, a major site of high affinity with an apparent KD of 0.4 microM and a minor low-affinity site with an apparent KD of 4.6 microM. High affinity binding occurred at a single site on peptide 205-227 (KD = 0.27 microM) and was competed by chlorpromazine but not by alpha-Btx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854750 TI - Partitioning of fluorescent phospholipid probes between different bilayer environments. Estimation of the free energy of interlipid hydrogen bonding. AB - Fluorescence spectroscopy has been used to monitor the partitioning of a series of exchangeable neutral phospholipid probes, labeled with carbazole, indolyl or diphenylhexatrienyl moieties, between large unilamellar vesicles containing 1 palmitoyl-2-oleoylphosphatidylcholine (POPC), 1,2-dioleoyloxy-3 (trimethylammonio) propane (DOTAP) or N-hexadecyl-N-(9-octadecenyl)-N,N dimethylammonium chloride (HODMA). Phosphatidylethanolamine (PE) probes desorb from POPC-containing vesicles at markedly slower rates than do phosphatidylcholine (PC) probes with the same acyl chains. The rate of probe desorption from such vesicles is progressively enhanced by successive N methylations of the amino group but not by methylation of C-2 of the ethanolamine moiety, a modification that leaves unaltered the hydrogen-bonding capacity of the polar headgroup. By contrast, the rates of desorption of different probes (with the same acyl chains) from HODMA or from DOTAP vesicles are much more comparable and reflect no clear systematic influence of the headgroup hydrogen-bonding capacity. Equilibrium-partitioning measurements indicate that the relative affinities of different probes for PC-rich vesicles, in competition with HODMA or DOTAP vesicles, increase with increasing hydrogen-bonding capacity of the probe headgroup in the order PC less than N,N-dimethyl PE less than N-methyl PE less than PE approximately phosphatidyl-2-amino-1-propanol. From such partitioning data, we estimate that interlipid hydrogen-bonding interactions (in competition with lipid-water interactions) contribute roughly -300 cal mol-1 to the free energy of a PE molecule in a hydrated liquid-crystalline phospholipid bilayer; this free-energy contribution is somewhat smaller, but still significant, for N mono- and dimethylated PE's. PMID- 1854751 TI - Mechanism of altered renal glutaminase gene expression in response to chronic acidosis. AB - Increased rat renal ammoniagenesis is sustained during chronic metabolic acidosis by the cell-specific induction of the regulatory enzymes of glutamine catabolism and of gluconeogenesis. A glutaminase-specific cDNA hybridizes to 6.0- and 3.4-kb mRNAs that are contained in total or poly(A)+ RNA isolated from rat kidney. When translated in a rabbit reticulocyte lysate, each of the fractionated mRNAs produces the 72-kDa precursor of the mitochondrial glutaminase. The levels of both mRNAs are increased 5-fold within 1 day following onset of chronic acidosis and reach a maximum (8-fold) after 5 days. During recovery from chronic acidosis, the levels of the glutaminase mRNAs are returned to normal within 1 day. The observed changes in mRNA levels correlate with equivalent changes in the relative levels of translatable glutaminase mRNA. Nuclear run-on assays indicate that the rate of transcription of the renal phosphoenolpyruvate carboxykinase gene is increased and decreased in response to onset and recovery from chronic acidosis, respectively. In contrast, the rates of transcription of the glutaminase and beta actin genes are unaffected by alterations in acid-base balance. Thus, the increase in renal glutaminase activity during chronic acidosis results from an equivalent increase in the levels of total and translatable glutaminase mRNAs which apparently results from an increased stability of the glutaminase mRNA. PMID- 1854752 TI - HIV-1 Rev expressed in recombinant Escherichia coli: purification, polymerization, and conformational properties. AB - The high-level expression of HIV-1 Rev in Escherichia coli is described. Protein in crude bacterial extracts was dissociated from bound nucleic acid with urea. A simple purification and renaturation protocol, monitored by circular dichroism, is described which results in high yields of pure protein. The purified protein binds with high affinity to the Rev-responsive element mRNA and has nativelike spectroscopic properties. The protein exhibits concentration-dependent self association as judged by analytical ultracentrifugation and gel filtration measurements. Purified Rev showed reversible heat-induced aggregation over the temperature range 0-30 degrees C. This hydrophobic-driven and nonspecific protein association was inhibited by low concentrations of sulfate ions. Rev solutions at greater than 80 micrograms/mL, incubated at 0-4 degrees C, slowly polymerized to form long hollow fibers of 20-nm diameter. Filament formation occurs at a lower protein concentration and more rapidly in the presence of Rev-responsive mRNA. The nucleic acid containing filaments are about 8 nm in diameter and up to 0.4 micron in length. On the basis of physical properties of the purified protein, we have suggested that in the nucleus of infected cells, Rev binding to the Rev responsive region of env mRNA may be followed by helical polymerization of the protein which results in coating of the nucleic acid. Coated nucleic acid could be protected from splicing in the nucleus and exported to the cytoplasm. PMID- 1854753 TI - Relative affinities of divalent polyamines and of their N-methylated analogues for helical DNA determined by 23Na NMR. AB - Interactions of divalent polyamines with double-helical DNA in aqueous solution are investigated by monitoring the decrease in 23Na NMR relaxation rates as NaDNA is titrated with H3N(+)-(CH2)m-+NH3, where m = 3, 4, 5, or 6. Analogous measurements are made for the same homologous series of methylated polyamines (methonium ions). The dependence of the 23Na relaxation rates on the amount of added divalent cation (M2+) is analyzed quantitatively in terms of a two-state model. The sodium ions are assumed to be in rapid exchange between a "bound" state, where they are close enough to DNA so that it affects their relaxation rate, and a "free" state in bulk solution, where their relaxation rate is the same as in solutions containing no DNA. The distribution of Na+ and M2+ between these states is described quantitatively in terms of an ion-exchange parameter: DM = (pMB)(1-pNaB)n/(pNaB)n(1-pMB), where pNaB and pMB are the fractions of Na+ and M2+ that are close enough to DNA to be considered bound (by the NMR criterion), and n is the number of sodium ions displaced from DNA by the binding of one M2+ ion. For each of the polyamines and methonium ions investigated here, equations derived from this two-state model yield acceptable fittings of the titration curves if roNa, the number of sodium ions bound per DNA phosphate when no competing cations are present, is assigned a value between 0.6 and 1.00. Within this range, changing the value assigned to roNa does change the best fitted values of DM determined for these polyamines (DH) and for the methonium ions (DMe) but does not alter the following conclusions about the trends in these parameters. (1) For polyamines and methonium ions of the same m, DH exceeds DMe by factors that are significantly larger for m = 3 and 4 than for m = 5 and 6. (2) DH for m = 3 and 4 is larger than DH for m = 5 and 6. (3) DMe for m = 3 and 4 is smaller than DMe for m = 5 and 6. PMID- 1854754 TI - In vitro and in vivo DNA bonding by the CC-1065 analogue U-73975. AB - CC-1065, a cyclopropylpyrroloindole (CPI), is a highly potent antitumor DNA alkylating agent. We have devised a simple method to detect CPI bonding sites on double-stranded DNA (dsDNA). The technique utilizes a modified form of bacteriophage T7 polymerase, Sequenase, to synthesize a radiolabeled nascent strand from dsDNA that has been reacted in vitro with the CC-1065 analogue U 73975 (adozelesin). The reaction products were electrophoresed on sequencing gels containing 8 M urea and visualized by autoradiography. The transit of this DNA polymerase is inhibited at the sites where CPIs are bound to the template strand. Thus, the enzyme stalls or stops at the nucleotide immediately adjacent to the modified base, resulting in the accumulation of DNA strands at these sites and in diminished read-through beyond these sites in a set of CPI-treated DNA molecules. The precise positions of polymerase inhibition can be determined by comparison of CPI-treated and unreacted DNA reactions. This modified dideoxynucleotide sequencing technique has been used to establish the sequence selectivity of U 73975. Approximately 1 kilobase of dsDNA has been analyzed to derive a consensus canonical bonding sequence, 5'(T/A)-T/A-T-A*-(C/G)-(G), where A* is the site of U 73975 alkylation and parentheses denote deoxynucleotide preferences. Noncanonical sites were also found at poly(A) sites. This technique yielded a consensus sequence for U-73975 bonding that is similar to, but not identical with, the published consensus obtained for CC-1065 by a modified Maxam and Gilbert sequencing technique. We have also examined the bonding of [3H]U-73975 to the DNA of viable cultured mammalian cells, using gel electrophoresis and autoradiographic techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854755 TI - Thermodynamics of DNA duplexes with adjacent G.A mismatches. AB - The sequence 5'-d(ATGAGCGAAT) forms a very stable self-complementary duplex with four G.A mismatch base pairs (underlined) out of ten total base pairs [Li et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 26-30]. The conformation is in the general B-family and is stabilized by base-pair hydrogen bonding of an unusual type, by favorable base dipole orientations, and by extensive purine-purine stacking at the mismatched sites. We have synthesized 13 decamers with systematic variations in the sequence above to determine how the flanking sequences, the number of G.A mismatches, and the mismatch sequence order (5'-GA-3' or 5'-AG-3') affect the duplex stability. Changing A.T to G.C base pairs in sequences flanking the mismatches stabilizes the duplexes, but only to the extent observed with B form DNA. The sequence 5'-pyrimidine-GA-purine-3', however, is considerably more stable than 5'-purine-GA-pyrimidine-3'. The most stable sequences with two pairs of adjacent G.A mismatches have thermodynamic parameters for duplex formation that are comparable to those for fully Watson-Crick base-paired duplexes. Similar sequences with single G.A pairs are much less stable than sequences with adjacent G.A mismatches. Reversing the mismatch order from 5'-GA-3' to 5'-AG-3' results in an oligomer that does not form a duplex. These results agree with predictions from the model derived from NMR and molecular mechanics and indicate that the sequence 5'-pyrimidine-GA-purine-3' forms a stable conformational unit that fits quite well into a B-form double helix.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854756 TI - Observation of multiple radical pair states in photosystem 2 reaction centers. AB - Charge recombination of the primary radical pair in D1/D2 reaction centers from photosystem 2 has been studied by time-resolved fluorescence and absorption spectroscopy. The kinetics of the primary radical pair are multiexponential and exhibit at least two lifetimes of 20 and 52 ns. In addition, a third lifetime of approximately 500 ps also appears to be present. These multiexponential charge recombination kinetics reflect either different conformational states of D1/D2 reaction centers, with the different conformers exhibiting different radical pair lifetimes, or relaxations in the free energy of the radical pair state. Whichever model is invoked, the free energies of formation of the different radical pair states exhibit a linear temperature dependence from 100 to 220 K, indicating that they are dominated by entropy with negligible enthalpy contributions. These results are in agreement with previous determinations of the thermodynamics that govern primary charge separation in both D1/D2 reaction centers [Booth, P.J., Crystall, B., Giorgi, L. B., Barber, J., Klug, D.R., & Porter, G. (1990) Biochim. Biophys. Acta 1016, 141-152] and reaction centers of purple bacteria [Woodbury, N.W.T., & Parson, W.W. (1984) Biochim. Biophys. Acta 767, 345-361]. It is possible that these observations reflect structural changes that accompanying primary charge separation and assist in stabilization of the radical pair state thus optimizing the efficiency of primary electron transfer. PMID- 1854757 TI - The conserved, buried aspartic acid in oxidized Escherichia coli thioredoxin has a pKa of 7.5. Its titration produces a related shift in global stability. AB - Aspartic acid 26 in Escherichia coli thioredoxin is located at the bottom of a hydrophobic cavity, near the redox-active disulfide of the active site. Asp 26 is embedded in the protein except for part of the surface of one carboxyl oxygen. The high degree of evolutionary conversion of Asp 26 suggests that it plays a critical role in thioredoxin function. We have determined the pKa of Asp 26 by a novel electrophoretic method based on the relative electrophoretic mobilities of wild-type thioredoxin and of D26A thioredoxin (with Asp 26 replaced by alanine). The pKa of Asp 26 determined by this technique is 7.5, more than 3 units above the pKa of a solvated carboxyl side chain. The titration of Asp 26 is thermodynamically linked to the stability of thioredoxin. As expected if thioredoxin stability depends on the ionization state of Asp 26, delta Go WT, the free energy of the cooperative denaturation reaction of wild-type thioredoxin by guanidine hydrochloride, varies with pH in a sigmoidal fashion in the vicinity of pH 7.5. Over the same pH range, the free energy for D26A folding, delta Go D26A, is pH independent and D26A is highly stabilized compared to wild type. From the thermodynamic cycle describing the linkage of Asp 26 titration to thioredoxin stability, the difference in free energy between wild-type thioredoxin with protonated Asp 26 and wild-type thioredoxin with deprotonated Asp 26, delta delta Go (COOH----COO-), is calculated to be 4.9 kcal/mol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854758 TI - Fluorescence analysis of calmodulin mutants containing tryptophan: conformational changes induced by calmodulin-binding peptides from myosin light chain kinase and protein kinase II. AB - Peptide-induced conformational changes in five isofunctional mutants of calmodulin (CaM), each bearing a single tryptophan residue either at the seventh position of each of the four calcium-binding loops (i.e., amino acids 26, 62, 99, and 135) or in the central helix (amino acid 81) were studied by using fluorescence spectroscopy. The peptides RS20F and RS20CK correspond to CaM binding amino acid sequence segments of either nonmuscle myosin light chain kinase (nmMLCK) or calmodulin-dependent protein kinase II (CaMPK-II), respectively. Both steady-state and time-resolved fluorescence data were collected from the various peptide-CaM complexes. Steady-state fluorescence intensity measurements indicated that, in the presence of an excess of calcium, both peptides bind to the calmodulin mutants with a 1:1 stoichiometry. The tryptophans located in loops I and IV exhibited red-shifted emission maxima (356 nm), high quantum yields (0.3), and long average lifetimes (6 ns). They responded in a similar manner to peptide binding, by only slight changes in their fluorescence features. In contrast, the fluorescence intensity of the tryptophans in loops II and III decreased markedly, and their fluorescence spectrum was blue shifted upon peptide binding. Analysis of the tryptophan fluorescence decay of the last mentioned calmodulins supports a model in which the equilibrium between two (Trp-99) or three (Trp-62) states of these tryptophan residues, each characterized by a different lifetime, was altered toward the blue-shifted short lifetime component upon peptide binding. Taken together, these data provide new evidence that both lobes of calmodulin are involved in peptide binding. Both peptides induced similar changes in the fluorescence properties of the tryptophan residues located in the calcium-binding loops, with the exception of calmodulin with Trp-135. For this last mentioned calmodulin, slight differences were observed. Tryptophan in the central helix responded differently to RS20F and RS20CK binding. RS20F binding induced a red-shift in the emission maximum of Trp 81 while RS20CK induced a blue-shift. The quenching rate of Trp-81 by iodide was slightly reduced upon RS20CK binding, while RS20F induced a 2-fold increase. These results provide evidence that the environment of Trp-81 is different in each case and are, therefore, consistent with the hypothesis that the central helix can play a differential role in the recognition of, or response to, CaM binding structures. PMID- 1854759 TI - Photoaffinity labeling of human serum vitamin D binding protein and chemical cleavages of the labeled protein: identification of an 11.5-kDa peptide containing the putative 25-hydroxyvitamin D3 binding site. AB - In this paper, we describe photoaffinity labeling and related studies of human serum vitamin D binding protein (hDBP) with 25-hydroxyvitamin D3 3 beta-3'-[N-(4 azido-2-nitrophenyl)amino]propyl ether (25-ANE) and its radiolabeled counterpart, i.e., 25-hydroxyvitamin D3 3 beta-3'-[N-(4-azido-2-nitro-[3,5 3H]phenyl)amino]propyl ether (3H-25-ANE) (Ray et al., 1986, 1991). We have carried out studies to demonstrate that (1) 25-ANE competes with 25-OH-D3 for the binding site of the latter in hDBP and (2) 3H-25-ANE is capable of covalently labeling the hDBP molecule when exposed to UV light. Treatment of a sample of purified hDBP, labeled with 3H-25-ANE, with BNPS-skatole produced two Coomassie Blue stained peptide fragments, and the majority of the radioactivity was associated with the smaller of the two peptide fragments (16.5 kDa). On the other hand, cleavage of the labeled protein with cyanogen bromide produced a peptide (11.5 kDa) containing most of the covalently attached radioactivity. Considering the primary amino acid structure of hDBP, this peptide fragment (11.5 kDa) represents the N-terminus through residue 108 of the intact protein. Thus, our results tentatively identify this segment of the protein containing the binding pocket for 25-OH-D3. PMID- 1854760 TI - Metal-induced changes in the fluorescence properties of tyrosine and tryptophan site-specific mutants of oncomodulin. AB - Oncomodulin is a 108-residue, oncodevelopmental protein containing two calcium binding sites identified as the CD- and EF-loops. The protein contains no tryptophan and only two tyrosine residues, one which is a calcium ligand in the CD-loop (Tyr-57) and one which lies in the flanking D-helix of this loop (Tyr 65). Site-specific mutagenesis was performed to yield five mutants, two with phenylalanine substituted for tyrosine in positions 57 and 65 and three with tryptophan substituted into position 57 in the CD-loop, position 65 in the D helix, and position 96 in the EF-loop. The single Tyr-containing mutants demonstrated that position 57 was perturbed to a significantly greater extent than position 65 upon calcium binding. Although both tyrosine residues responded to decalcification, the fluorescence intensity changes were in opposite directions, with the more dominant Tyr-57 accounting for the majority of the intrinsic fluorescence observed in native oncomodulin. The substitution of tryptophan for each tyrosyl residue revealed that in both positions the tryptophan resided in polar, conformationally heterogeneous environments. The environment of Trp-57 was affected by Ca2+ binding to a much greater extent compared to that of Trp-65. Only 1 equiv of Ca2+ was required to produce greater than 70% of the Trp fluorescence changes in positions 57 and 65, indicating that Ca2+ binding to the higher affinity EF-loop had a pronounced effect on the protein structure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854761 TI - Heart transplantation in females. AB - To confirm reports of a higher rate of rejection in female recipients of cardiac allografts and to determine whether infection rates and actuarial survival differ from that in males, we reviewed the results of 150 consecutive heart transplant procedures. Of these, 27 were in females and 123 were in males. Three different regimens were used over a 5-year period: group 1 (n = 37), cyclosporine and prednisolone; group 2 (n = 61), cyclosporine, azathioprine, and prednisolone; group 3 (n = 52), cyclosporine and azathioprine. All groups received a 7- to 10 day induction course with antithymocyte globulin. Female recipients had significantly more rejection episodes than male recipients to 3 months after transplantation (females 2.3 vs males 1.5 episodes/patient, p less than 0.01) and to 12 months (females 2.4 vs males 1.5 episodes/patient, p less than 0.02). These differences were largely caused by higher rates of rejection in females in both "double" therapy groups (groups 1 and 3). All surviving females in group 3 required the addition of maintenance steroids to control rejection. Gender mismatching of donors (male donor, female recipient) was identified as a factor associated with this requirement for conversion. Augmented treatment for rejection resulted in a higher rate of infection at 12 months in female recipients (females 1.5 vs males 0.7 episodes/patient, p less than 0.02), yet no female died of infection, and actuarial survival was comparable to that in male recipients. In view of the propensity of females to reject more frequently and earlier than males, triple therapy is currently the regimen of choice for female patients in the first 3 to 6 months after heart transplantation. Steroid withdrawal may be possible at a later time in those in whom this is indicated. PMID- 1854762 TI - Heart transplantation: hemodynamics over a five-year period. AB - Long-term hemodynamic evaluation after heart transplantation has rarely been reported. Fifty-seven heart transplant recipients (mean age, 42.1 years: range, 22 to 56 years) were investigated with annual cardiac catheterization. Mean follow-up was 2.2 years (range, 1 to 7 years). Years 1 through 5 were evaluated statistically. Hemodynamic variables did not change significantly during the 5 year period. Mean aortic pressure (105 +/- 16 to 115 +/- 17 mm Hg, minimum and maximum annual average value +/- SD of the 5-year period) and LVEDP (13 +/- 6 to 15 +/- 7 mm Hg) were slightly elevated. Borderline values were found for mean pulmonary artery pressure (18 +/- 4 to 21 +/- 5 mm Hg), systemic vascular resistance (1407 +/- 227 to 1487 +/- 409 dynes.sec.cm-5), pulmonary vascular resistance (86 +/- 42 to 118 +/- 66 dynes.sec.cm-5), and heart rate (85 +/- 17 to 95 +/- 14 beats/min). Mean right atrial pressure (5 +/- 2 to 8 +/- 4 mm Hg), cardiac index (2.8 +/- 0.6 to 3.5 +/- 1.1 L/min/m2), end-diastolic volume (111 +/ 37 to 137 +/- 35 ml) and ejection fraction (69% +/- 10% to 75% +/- 9%) were in the normal range. Pressure-volume loops for each year excluded the development of either restrictive or dilated cardiomyopathy with time. Contractility, as measured by imposing afterload stress, was normal in 12 of 14 representative patients. Prevalence of coronary abnormalities (circumscript coronary stenoses, diffuse vessel obliteration or dilated angiopathy) increased from 14.9% in the first to 66.7% in the fifth year. Of the patients, 93% received antihypertensive drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854763 TI - Prospective study of the safety and financial benefit of ketoconazole as adjunctive therapy to cyclosporine after heart transplantation. AB - In a prospective study of the relative safety and potential benefit of concomitant ketoconazole and cyclosporine after heart transplantation, 15 transplant recipients were followed up for up to 1 year (mean, 10.7 months) after ketoconazole was added to their immunosuppressive regimen of cyclosporine, prednisone, and azathioprine, and these patients were compared with a matched cohort over the same time. There was an 88% reduction in the mean (+/- SD) dose of cyclosporine, from 394 (115) mg/day to 47 (21) mg/day (p less than 0.0005) in the ketoconazole group, compared with an insignificant change in the control group. The projected annual cost of cyclosporine was reduced by 88%, with a 72% reduction in the projected cost of immunosuppressive drugs and prophylactic antifungal therapy, from a mean of $6800 to $1862 per year per transplant recipient in the ketoconazole-treated group. Other beneficial effects found over the study period included a significant reduction in the mean and diastolic systemic arterial pressure and a significant reduction in serum cholesterol. The mean total serum cholesterol fell from 265 (44) to 204 (38) mg/dl in the ketoconazole group but did not change significantly in the control group (p less than 0.005). Low-density lipoprotein cholesterol also fell from a mean of 167 (32) mg/dl to 112 (28) mg/dl (p less than 0.005). Renal function was not significantly affected by ketoconazole when compared with the control group. Ketoconazole and other drugs of potential use in organ transplant recipients should be evaluated for financial as well as for other potential clinical benefits in the long-term management of these patients. PMID- 1854764 TI - Long-term preservation of renal function in hypertensive heart transplant recipients treated with enalapril and a diuretic. AB - Hypertension and progressive deterioration in renal function are commonly seen in heart transplant recipients treated for the long term with cyclosporine. Because angiotensin converting enzyme inhibitors have been associated with amelioration of renal dysfunction in some patients with hypertension and preexisting mild moderate kidney failure, we treated nine hypertensive recipients of orthotopic heart transplants with enalapril (11 +/- 2 mg/day) and furosemide (62 +/- 15 mg/day) for 23 +/- 4 months. Most of the enalapril dose was given at bedtime, which minimized nocturnal and early morning hypertension. In addition to controlling blood pressure (154 +/- 6/100 +/- 2 mm Hg before enalapril vs 120 +/- 5/81 +/- 2 mm Hg currently; p less than 0.001 for both systolic and diastolic blood pressures by paired t test), there has been no increase in serum creatinine level over 684 +/- 102 days of follow-up (1.88 +/- 0.20 mg/dl before enalapril vs 1.81 +/- 0.17 mg/dl currently; p greater than 0.70). This is unlikely to be caused by the reduction in daily cyclosporine dose (492 +/- 60 mg/day before enalapril to 305 +/- 47 mg/day currently) because there were no significant changes in mean blood cyclosporine level (which has been maintained between 100 and 500 ng/ml). Treatment of hypertension with enalapril and a diuretic after heart transplantation may help prevent or delay the impairment of renal function often seen during prolonged cyclosporine therapy. PMID- 1854765 TI - Late infection in cardiac allograft recipients: profiles, incidence, and outcome. AB - Infection continues to cause substantial morbidity and mortality after heart transplantation. Studies focusing on this problem have concentrated on the early posttransplant period, and it is uncertain to what extent infection continues to add to morbidity later after transplantation. Fifty-four patients surviving at least 1 year after heart transplantation made up the study population in this study, and they were surveyed for infections beyond 1 year. In this group there were 15 infections, an incidence of 0.3 infections per patient or 0.016 infections per patient-months of follow-up. Only nine of these infections necessitated hospitalization; two, however, were fatal. Actuarial risk of all late infections and late infections necessitating hospitalization was 13% and 6%, respectively, at 2 years. As expected, bacterial infections made up the largest group (60%), followed by viral disease (27%). Two patients had pulmonary infections, one with Aspergillus and one with Pneumocystis. These data demonstrate that although rates of infection in heart recipients continue to exceed those in the general population, the rates are considerably lower than those in what is seen early after heart transplantation. Despite this, the more unusual infectious agents associated with immune compromise continue to be present. PMID- 1854766 TI - Catabolism of high energy phosphates during long-term cold storage of donor hearts: effects of extra- and intracellular fluid-type cardioplegic solutions and calcium channel blockers. AB - Dog hearts were harvested and stored cold (0.5 degree C) for 24-hours. Cardiac arrest was induced by means of low-sodium and calcium-free cardioplegic (n = 6) or hyperkalemic cardioplegic (n = 6) solution. Nifedipine (2 micrograms/gm estimated heart weight) was added to each cardioplegic solution in two additional groups (n = 6 each). High energy phosphates (creatine phosphate and adenosine triphosphate) and catabolites (adenosine diphosphate and monophosphate, adenosine, inosine, hypoxanthine, xanthine) were determined in the myocardium before and during 24 hours of cold storage. With use of the standard hyperkalemic cardioplegic solution, breakdown of high energy phosphates was less pronounced than after the use of a low sodium, calcium-free solution: after 24 hours of cold storage myocardial ATP content was 57% of control versus 32% (p less than 0.05). The addition of nifedipine to the hyperkalemic cardioplegic solution delayed ATP breakdown during the first hours of cold storage: at 5 hours of preservation the myocardial ATP level was significantly higher (p less than 0.05) than in hearts preserved without nifedipine. Addition of nifedipine to the low-sodium, calcium free solution did not influence catabolism of high energy phosphates significantly. It is concluded that preservation of high energy phosphates during long-term cold storage of donor hearts can be best achieved by simultaneous myocardial metabolic blockade at two specific sites: at the "fast" sodium potassium channels by hyperkalemic depolarization and at the "slow" channels by means of calcium channel blockers. PMID- 1854767 TI - Extending cardiac allograft ischemic time and donor age: effect on survival and long-term cardiac function. AB - Of 219 heart transplant patients with follow up for at least 3 months after transplantation, cardiac allograft ischemic time was more than 4 hours in 28% and more than 5 hours in 10%. In 1988 and 1989 grafts with ischemic times longer than 4 hours were used in 44% and 45% of cases, respectively. Overall, donor age has been 35 or more years in 22% and 45 or more in 9%. In 1989 donor age was 35 or more years in 39% of cases and 45 or more in 18%. Fifteen of 20 grafts from donors 45 years or older were used for patients aged 50 or older. There was no relationship between donor age or ischemic time and 90-day graft loss. At 3 and 12 months, cardiac function, assessed by treadmill exercise duration, radionuclide angiography, and rest and peak supine exercise hemodynamics, was also unrelated to donor age or ischemic time. Therefore by careful selection of appropriate donors, extending both graft ischemic time and donor age has increased the potential donor pool and has not to date been associated with increased graft loss or adverse effects on cardiac function 3 months and 1 year after heart transplantation. PMID- 1854768 TI - Functional studies of the heart during a 24-hour preservation using a new autoperfusion preparation. AB - Serial cardiac function studies were carried out during a 24-hour preservation in a new autoperfusion multiorgan preparation using adult Yorkshire swine (n = 8). The heart was removed with the lungs, liver, pancreas, duodenum, and both kidneys while they were still perfused by the heart and oxygenated by the lungs. The organs were placed in a 32 degrees C bath solution containing lactated Ringer's, heparin, and neomycin. Fresh blood and a solution containing glucose (10%) with potassium chloride (2 gm/L), calcium chloride (1 gm/L), heparin sodium (100 mg/L), mannitol (12.5 gm/L), insulin (100 U/L), metronidazole hydrochloride (500 mg/L), penicillin (1,000,000 U/L), and methylprednisolone (250 mg/L) were given slowly through the portal vein. A fat emulsion 2 ml, methylprednisolone 30 mg, and heparin sodium 20 mg were given through the portal vein every 2 hours. No inotropic drugs were used. Aortic systolic pressures ranged from 79 to 97 mm Hg; the aortic diastolic pressures ranged from 44 to 61 mm Hg. Central venous pressures ranged from 0.4 to 2.0 mm Hg, and the heart rate was 69 to 81 beats/min. Left ventricular maximum dp/dt ranged from 1405 to 1836 mm Hg/sec, and maximum dp/dt/p ranged from 17.0 to 26.2 (sec-1). Aortic blood flow ranged from 1.2 to 1.6 L/min, and systemic resistance ranged from 33 to 53 U. Lactic acid decreased from 8.15 to 2.80 mmol/L. Myocardium wet/dry weight ratio after preservation averaged 5.13 (vs 5.09 for control). These results suggest that the heart may be preserved up to 24 hours with minimal change in function with this new autoperfusion preparation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854769 TI - Major histocompatibility antigens in transplanted human hearts before perfusion. AB - The expression of major histocompatibility class I and II antigens is described in human normal donor hearts before perfusion with recipients' blood. Class I and II major histocompatibility antigens were found on interstitial but not on myocardial cells. Endothelial cells accounted for most of the generic class I reactions (that is, W6/32 and beta 2 microglobulin), and endothelial cells accounted for most of the HLA-DR and -DP reactivity. HLA-DQ antigens were not found in this series of normal donor hearts. The earliest time we were able to identify HLA-DQ antigens during the follow-up biopsies from these patients was 1 week after the allograft had been in place. Macrophages accounted for little of the class II reactivity. Variations in the HLA-DQ antigen expression on endothelial cells may be useful in the follow-up of transplanted hearts, considering that these antigens have been found to be more susceptible to the effects of interferon-gamma than either HLA-DR or -DP. PMID- 1854770 TI - Problems in assessment of pulmonary parenchymal consolidation in heart transplant candidates. AB - Radiologic assessment of the cause of pulmonary parenchymal consolidation in end stage heart failure may be difficult. From August 1982 to May 1989, 22 patients being considered for orthotopic cardiac allografts had parenchymal consolidation on their chest radiographs, most commonly in the right lower lobe. Our purpose was to determine from standard radiologic studies whether this consolidation represented alveolar pulmonary edema in an atypical basal distribution, pneumonia, or pulmonary infarction. This differentiation is important because pneumonia is an absolute and infarction is a relative contraindication to surgery, whereas successful transplantation can be performed in a setting of pulmonary edema. The chest radiographs were reviewed retrospectively. When available, pulmonary angiograms, nuclear medicine ventilation/perfusion scans, and needle biopsy findings were also evaluated. The radiologic assessment was correlated with the results of surgical, autopsy, or clinical outcome. None of the conventional modalities was very accurate--the plain chest film was correct in only 63%, nuclear medicine studies in 50%. Angiography was the single most useful test, with an accuracy of 75%. PMID- 1854771 TI - Heart-lung xenotransplantation in primates. AB - Heart and heart-lung xenografts are a potential solution to the shortage of donors. Concern over the adequacy of conventional immunosuppression in prevention of xenograft rejection, however, has hindered their use. Cyclosporine has not been successful in suppressing the rejection process in cardiac xenotransplantation, and other methods of immunosuppression need to be investigated. Therefore we studied the effect of preoperative total lymphoid irradiation (TLI) in combination with cyclosporine in a primate heart-lung xenograft model using cynomolgus monkey donors and baboon recipients. Heart-lung grafts were harvested from donors and transplanted orthotopically in baboons with use of cardiopulmonary bypass. Recipients were treated in one of three groups: (1) cyclosporine and steroids (controls), (2) cyclosporine and steroids plus TLI 20 Gy, or (3) cyclosporine, steroids, antithymocyte globulin, and TLI 6 Gy. Mean survival time of the baboons treated with cyclosporine and steroids was 8 +/- 0.6 days. The group receiving 20 Gy TLI had prohibitive perioperative mortality; however, one baboon lived an additional 90 days, and at autopsy the heart showed minimal rejection. Treatment with TLI at 6 Gy in combination with cyclosporine, antithymocyte globulin, and steroids comparatively prolonged survival (16 +/- 7.8 vs 8 +/- 0.6 days; p less than 0.001), and all animals in this group died of infection, with only minimal evidence of heart rejection noted in animals surviving 30 days. We conclude that the addition of TLI and antithymocyte globulin to cyclosporine-based standard immunosuppression is a potent immunosuppressant in heart-lung xenotransplantation; nevertheless, infection remains a common complication. PMID- 1854772 TI - Obesity and hyperlipidemia after heart transplantation. AB - Body weight and serum lipids were retrospectively analyzed in 54 heart transplant recipients (mean age, 43 years; 80% male) who survived at least 1 year. Data were collected preoperatively and at 1, 2, and 3 years after heart transplantation. Analysis was performed using item frequencies, analysis of variance, and Pearson product moment correlations. From preoperatively to 1 year after heart transplantation, the weight of patients increased significantly from 100% to 117% of ideal body weight and did not decrease significantly over the first 3 postoperative years. Serum cholesterol and triglyceride values increased significantly from preoperative values of 175 mg/dl and 139 mg/dl, respectively, to 1-year postoperative values of more than 200 mg/dl (p = 0.01). Serum cholesterol, but not triglyceride levels, decreased significantly 3 years after surgery as compared with 1 year after surgery. In addition, overall serum cholesterol and triglyceride levels were higher in patients with coronary artery disease (248 mg/dl) than with dilated cardiomyopathy (207 mg/dl). Serum high density lipoproteins remained within acceptable clinical levels (greater than 35 mg/dl) during all 3 postoperative years. Serum low-density lipoproteins, elevated (139 mg/dl) for the first 2 postoperative years, fell to within the desirable range (less than 130 mg/dl) by the third posttransplant year. Heart function was normal throughout all 3 years. Six patients (11%) were given lipid-lowering medications after heart transplantation (mean, 25 postoperative months).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854773 TI - Quality of life after orthotopic heart transplantation. AB - During the last decade heart transplantation has become the chosen method to treat terminally ill patients suffering from severe cardiac illness. It was the aim of our study to retrospectively survey life quality of donor organ recipients who underwent heart transplantation during the first years of transplantation at our center (1984 through 1987). Thirty-five patients were asked to evaluate their postoperative improvement or deterioration and their satisfaction with the level reached on visual scales. Life quality was defined in nine areas: physical, emotional, mental, vocational, and sexual status, financial situation, leisure activities, partnership, and overall life quality. The following results were obtained: (1) our former patients informed us about a distinct improvement in almost all dimensions (except financial situation). We found an absolute increase in life quality after heart transplantation. (2) Although improvement was ranked best for physical status, there was also a high amelioration in psychosocial fields. (3) A significant difference was seen between changes in condition and satisfaction in the financial situation (z = 2.3) and in partnership (z = 2.9), in which the latter was ranked higher. (4) The date of transplantation (less/more than 2 years ago) had no influence on the evaluation of postoperative life quality. PMID- 1854774 TI - Long-term assessment of renal function under cyclosporine in pediatric heart transplant recipients. AB - Renal function was monitored in eight children who were long-term survivors of heart transplantation and who were treated with cyclosporine. Both creatinine clearance and true glomerular filtration rate remained normal 17 to 69 months after transplantation. The survival rate was 80% at 6, 12, and 24 months, and the rejection rate in survivors was only 0.37. Thus adequacy of renal function can be preserved, without jeopardizing overall transplant results, by using small doses of cyclosporine. PMID- 1854775 TI - Unusual form of biliary obstruction in an orthotopic heart transplant recipient managed with cyclosporine. PMID- 1854776 TI - Tailored therapy before transplantation for treatment of advanced heart failure: effective use of vasodilators and diuretics. AB - Because of the limited supply of donor hearts, many candidates for heart transplantation must remain on waiting lists for several months. Although most such patients are considered to be refractory to standard therapy with vasodilators, diuretics, and digoxin, many will respond to a more intensive approach specifically tailored to hemodynamic goals in advanced heart failure. In this article the principles, design, and benefits of tailored therapy are reviewed. In addition, six common ideas about the management of advanced heart failure, derived from other patient populations, are shown to be myths. These myths are (1) that a low ejection fraction precludes good hemodynamics, exercise capacity, and survival; (2) that high ventricular filling pressures are necessary to maintain cardiac output in patients with chronic dilated heart failure; (3) that vasodilators in chronic advanced heart failure act primarily to increase ejection fraction and total stroke volume; (4) that hemodynamics measured during drug titration do not predict long-term benefit; (5) that the interval risk of deterioration and death without transplantation increases with time from evaluation; and (6) that for patients with low ejection fractions, heart transplantation is always better than medical therapy. PMID- 1854777 TI - Outpatient dobutamine for refractory congestive heart failure: advantages, techniques, and results. AB - Patients with refractory, end-stage congestive heart failure awaiting heart transplantation may be treated efficaciously with intermittent infusions of dobutamine given on an outpatient basis. The treatment appears to be well tolerated. Nevertheless, careful attention to electrolyte balance and arrhythmia control is essential to minimize the risk of sudden death. Use of a tunneled subcutaneous catheter essentially eliminates the risk of infection associated with this type of delivery system. Patients who have worsening heart failure while receiving dobutamine as outpatients should be fitted for a mechanical assist device before complications develop that may contraindicate transplantation. PMID- 1854778 TI - Coronary angioscopy in the diagnosis of graft coronary artery disease in heart transplant recipients. PMID- 1854779 TI - Changes in cellular membrane and paracellular conductances by amphotericin B in the epithelium of the bullfrog cornea. AB - In the isolated bullfrog cornea, measurements of DC electrical parameters in conjunction with AC impedance and ultrastructural analyses were used to determine the effects of 10(-5) M amphotericin B on epithelial cellular membrane and paracellular conductances. In NaCl Ringers, amphotericin B elicited a 3.5-fold increase in the specific apical membrane conductance (Ga/Ca); where Ga and Ca are the apical membrane conductance and capacitance, respectively. The basolateral membrane conductance (Gb) and the basolateral membrane capacitance (Cb) fell by 57% and 50%, respectively. In the paracellular pathway, the tight junctional complex (Gj) was unchanged whereas the lateral intercellular space resistance (Rp) decreased by 55%. The declines in Gb and Cb were suggestive of cell volume shrinkage because these changes were consistent with a previously described decline in intracellular K+ content and reduction in exposed basolateral membrane area to current flow. Ultrastructural analysis validated that amphotericin B caused cell volume shrinkage because there was: (1) increased folding of the basolateral membrane and waviness of the basal aspects- of the plasma membrane; (2) dilatation of the lateral intercellular spaces. This agreement suggests that intracellular activity decreased following exposure to amphotericin B which resulted in cell volume shrinkage and an impairment of Cl- uptake across the basolateral membrane. PMID- 1854780 TI - Mechanism of cell protrusion formation in electrical field: the role of actin. AB - An intense alternating current electrical field that imposes membrane-applied force on the cell surface can induce formation of cell protrusions (Popov, S.V. and Margolis, L.B. (1988) J. Cell Sci. 90, 379-389). This technique has been used to investigate the role of actin in the cell protrusion formation. Platinum replicas of the cytoskeleton were prepared to characterize the organization of the cytoskeleton in external force-induced protrusions. Bundles of microfilaments were found in the processes. A specific inhibitor of actin polymerization, cytochalasin B, as well as inhibitors of ATP synthesis (sodium azide and carbonyl m-chlorophenylhydrazone) did not change the morphology of electrical field generated protrusions, revealed by scanning electron microscopy. However, organization of the cytoskeleton inside the processes changed drastically using these inhibitors. The results of these experiments demonstrate that (i) Membrane applied force is sufficient to produce native-like cell protrusions, even in conditions where activity of the cytoskeleton is inhibited; (ii) Actin microfilaments can be organized into bundles directly under the action of membrane-applied force. The significance of these observations to cell protrusion formation under normal physiological conditions is discussed. PMID- 1854781 TI - Large liposomes containing ganglioside GM1 accumulate effectively in spleen. AB - Large liposomes, with a composition of egg phosphatidylcholine, cholesterol and ganglioside GM1, prepared by an extrusion method, were injected intravenously into mice. After 24 h, up to 50% of injected dose was accumulated in spleen compared with about 15% in spleen for liposomes containing no GM1. The effect of GM1 on spleen accumulation of liposomes was liposome size dependent. Only relatively large liposomes (d greater than 300 nm) showed high accumulation; smaller liposomes were progressively less accumulated. The spleen accumulation increased with increasing injection dose of the liposomes. It was noted that the enhanced uptake by spleen was accompanied by a decrease in the liver uptake, but the total uptake of liposomes by liver and spleen was not dependent on the diameter of liposome or the presence of the ganglioside GM1. Autoradiographs of fixed and sectioned spleen using 125I-labeled tyraminylinulin as a content marker for the liposomes, showed that liposomes localized at the reticular meshwork of the red pulp. These results suggest that larger liposomes containing GM1 are filtered by the spleen during the circulation in blood. The smaller ones with a mean diameter of less than 100 nm are not retained by the filter. The function of GM1 is to prevent liposomes from a rapid uptake by the liver so that liposomes may circulate through the spleen and be filtered. These results, together with the observation that the liposome-entrapped proteins were degraded by the spleen, suggest the potential use of these liposomes for specific drug delivery to the spleen. PMID- 1854782 TI - Intramolecular hydrogen bonding in cardiolipin. AB - Fourier transform infrared (FT-IR) spectroscopy was used to determine whether intramolecular hydrogen bonding between the C-OH and P-OH groups exists in beef heart cardiolipin (CL) or in hydrogenated beef heart cardiolipin (18:0-CL) as compared to the synthetic 2'-deoxy analogue of cardiolipin (16:0-dCL). Such intramolecular hydrogen bonding would provide a structural basis for proton conduction on the molecular level. In aqueous dispersions at 20 degrees C, both 18:0-CL and 16:0-dCL exist in the gel phase as bilayers with gel to liquid crystalline transitions (Tm) at 61 and 56 degrees C, respectively, whereas the unsaturated CL exists in the non-bilayer (hexagonal II) state. Evidence for intramolecular hydrogen bonding of the C-OH group in aqueous dispersions of 18:0 CL is provided by the large increase in Tm observed on changing the aqueous medium from H2O to D2O but specific hydrogen-bonded C-OH...PO2- species cannot be identified because water molecules also compete for the PO2- binding sites. However, C-OH...PO2- hydrogen bonds can be identified in dry films of the sodium salt of 18:0-CL or in CCl4 solution. In contrast, such hydrogen bonds cannot be formed in the deoxy analogue (16:0-dCL) indicating that the central C-OH group in 18:0-CL could provide a structural basis for proton conduction, involving the phosphate groups. PMID- 1854783 TI - Transmembrane distribution of sterol in the human erythrocyte. AB - The transbilayer cholesterol distribution of human erythrocytes was examined by two independent techniques, quenching of dehydroergosterol fluorescence and fluorescence photobleaching of NBD-cholesterol. Dehydroergosterol in conjunction with leaflet selective quenching showed that, at equilibrium, 75% of the sterol was localized to the inner leaflet of resealed erythrocyte ghosts. NBD cholesterol and fluorescence photobleaching displayed two diffusion values in both resealed ghosts and intact erythrocytes. The fractional contribution of the fast and slow diffusion constants of NBD-labelled cholesterol represent its inner and outer leaflet distribution. At room temperature the plasma membrane inner leaflet of erythrocyte ghosts as well as intact erythrocytes cells contained 78% of the plasma membrane sterol. The erythrocyte membrane transbilayer distribution of sterol was independent of temperature. In conclusion, dehydroergosterol and NBD-cholesterol data are consistent with an enrichment of cholesterol in the inner leaflet of the human erythrocyte. PMID- 1854784 TI - Na(+)-Ca2+ exchange activity in synaptic plasma membranes derived from the electric organ of Torpedo ocellata. AB - Synaptic plasma membranes obtained by hypo-osmotic treatment of purified Torpedo ocellata synaptosomes, contain an electrogenic Na(+)-Ca2+ exchange system. The dependence of the initial reaction rate on [Ca2+] reveals a single binding site for Ca2+ with an average apparent Km of 13.66 (S.D. = 12.07) microM [Ca2+] and maximal reaction velocity of Vmax = 11.33 (S.D. = 5.93) nmol/mg protein per s. The dependence of the initial rate of the Na+ gradient dependent Ca2+ influx on the internal [Na+] exhibits a sigmoidal curve which reaches half-maximal reaction rate at 170.8 (S.D. = 19.9) mM [Na+]. Addition of ATP gamma S does not change the K0.5 to Na+. The average Hill coefficient is 3.09 (S.D. = 0.86) indicating that 3 4 Na+ ions are exchanged for each Ca2+. Na+ gradient dependent Ca2+ uptake in Torpedo SPMs takes place also in the absence of K+ suggesting that K+ co transport is not obligatory. The temperature dependence of the initial and steady state rates of Na+ gradient dependent Ca2+ influx reveal that maximal reaction velocities of the Torpedo exchanger are attained between 15 and 20 degrees C. The energy of activation between 0 and 20 degrees C is 20,826 cal/mol. In comparison, rat brain synaptic plasma membrane Na(+)-Ca2+ exchanger reaches maximal reaction rates between 30 and 40 degrees C. Reconstitution of Torpedo or rat brain Na(+) Ca2+ exchangers into a membrane composed of either Torpedo or brain phospholipids, does not alter the temperature dependence of the native Torpedo or rat brain Na(+)-Ca2+ exchangers; inspite of considerable differences in the composition of the fatty acyl chains that are esterified to brain and Torpedo phospholipid head groups and differences in membrane fluidity that were detected. An ATP-dependent Ca2+ pump, which is insensitive to FCCP, is also present in the same synaptic membrane. PMID- 1854785 TI - High pressure antagonism of alcohol effects on the main phase-transition temperature of phospholipid membranes: biphasic response. AB - The combined effects of high pressure (up to 300 bar) and a homologous series of 1-alkanols (ethanol C2 to 1-tridecanol C13) were studied on the main phase transition temperature of dipalmitoylphosphatidylcholine (DPPC) vesicle membranes. It is known that short-chain alkanols depress and long-chain alkanols elevate the main transition temperature. The crossover from depression to elevation occurs at the carbon-chain length about C10-C12 in DPPC vesicle membranes coinciding with the cutoff chain-length where anesthetic potency suddenly disappears. Alkanols shorter than C8 linearly decreased the transition temperature and high pressure antagonized the temperature depression. Alkanols longer than C10 showed biphasic dose-response curves. High pressure enhanced the biphasic response. In addition, alkanols longer than the cutoff length depressed the transition temperature under high pressure at the low concentration range. These non-anesthetic alkanols may manifest anesthetic potency under high pressure. At higher concentrations, the temperature elevatory effect was accentuated by pressure. This biphasic effect of long-chain alkanols is not related to the 'interdigitation' associated with short-chain alkanols. The increment of the transition temperature by pressure was 0.0242 K bar-1 in the absence of alkanols. The volume change of the transition was estimated to be 27.7 cm3 mol-1. This value stayed constant to the limit of the present study of 300 bar. PMID- 1854787 TI - Phagocytosis of liposomes by macrophages: intracellular fate of liposomal malaria antigen. AB - Liposomes containing a synthetic recombinant protein were phagocytosed by macrophages, and the internalized protein was recycled to the cell surfaces where it was detected by enzyme-linked immunosorbent assay. The transit time of the liposome-encapsulated protein from initial phagocytosis of liposomes to appearance of protein on the surfaces of macrophages was determined by pulse chase experiments. The macrophages were pulsed with liposomes containing protein and chased with empty liposomes, and vice versa. The amount and rate of protein antigen expression at the cell surfaces depended on the quantity of encapsulated protein ingested by the macrophages. Although liposomes were rapidly taken up by macrophages, the liposome-encapsulated protein was antigenically expressed for a prolonged period (at least 24 h) on the cell surface. Liposomes were visualized inside vacuoles in the macrophages by immunogold electron microscopy. The liposomes accumulated along the peripheries of the vacuoles and many of them apparently remained intact for a long time (greater than 6 h). However, nonliposomal free protein was also detected in the cytoplasm surrounding these vacuoles, and it was concluded that the free protein in the cytoplasm was probably en route to the macrophage surface. Exposure of the cells to ammonium chloride did not inhibit the appearance of liposomal antigenic epitopes on the cell surface, and this suggests that expression of the liposomal antigenic epitopes at the surface was not a pH-sensitive phenomenon. There was no significant effect of a liposomal adjuvant, lipid A, on the rate or extent of surface expression of the liposomal protein. PMID- 1854786 TI - A statistical mechanical analysis of the effect of long-chain alcohols and high pressure upon the phase transition temperature of lipid bilayer membranes. AB - Long-chain n-alcohols decrease the main phase-transition temperature of lipid vesicle membranes at low concentrations but increase it at high concentrations. The nonlinear phenomenon is unrelated to the interdigitation and is analyzed by assuming that alcohols form solid solutions with solid as well as liquid phases. The biphasic response originates from the balance of the free energy difference of alcohols in the liquid and solid membranes (delta gA) and the alcohol-lipid interaction free energy difference (delta u) between the two phases. When delta gA less than 0 and delta u greater than 0, or delta gA less than delta u less than 0, the transition temperature decreases monotonously according to the increase in the alcohol concentration. When delta gA greater than 0 and delta u less than 0, or delta gA greater than delta u greater than 0, it increases monotonously. Biphasic response occurs with a minimum temperature when delta u greater than delta gA greater than 0, and with a maximum temperature when delta u less than delta gA less than 0. When the alcohol carbon-chain length becomes closer to the lipid carbon-chain length, delta u is equalized by delta gA, and the temperature minimum of the main transition is shifted to extremely low alcohol concentrations. Hence, long-chain alcohols predominantly elevate the main transition temperature and lose their anesthetic potency. High pressure decreased both delta gA and delta u. Presumably, high pressure improves the packing efficiency of liquid membranes and decreases the difference between the solid and liquid membrane properties. PMID- 1854788 TI - Regulation of Cl-dependent K transport by oxy-deoxyhemoglobin transitions in trout red cells. AB - The oxygenation of trout red cells opens a Cl-dependent K pathway inhibited by furosemide, and by inhibitors of the erythrocyte anion exchanger such as DIDS and niflumic acid. The trigger is the deoxy-oxy conformational change of hemoglobin. The binding of carbon monoxide to heme, which induces a similar conformational change, mimics the effect of oxygen. The possible mechanisms enabling molecular oxygen to control the transport protein are discussed. This oxygenation-activated K transport appears to play a regulatory role in the control of the extracellular K concentration. PMID- 1854789 TI - Characterization of glucosylceramide from plasma membranes of plant root cells. AB - Plasma membranes of oat root cells were isolated from intracellular membranes by subfractionation of the microsomal fraction using an aqueous polymer two-phase system. The plasma membranes originated from oat plants which were acclimated to dehydration by exposure to a repeated water-deficit stress program. Glucosylceramides was a major component of the plasma membrane lipids and amounted to 9% of the lipid of control plants and 5% of the lipid of acclimated plants. Structural analysis using FAB-MS showed only one type of glucosylceramides. The constituent monosaccharide was exclusively glucose and the sphingosine base was 4,8-sphingadienine. The fatty acid composition was determined to 24:1-OH, with only trace levels of non-hydroxy acids. The decrease in the level of glucosylceramides during acclimation to dehydration was accompanied by a corresponding decrease in phospholipids and increase in free sterols. PMID- 1854790 TI - Protein carboxyl methylation in kidney brush-border membranes. AB - Protein carboxyl methylation activity was detected in the cytosol and in purified brush-border membranes (BBM) from the kidney cortex. The protein carboxyl methyltransferase (PCMT) activity associated with the BBM was specific for endogenous membrane-bound protein substrates, while the cytosolic PCMT methylated exogenous substrates (ovalbumin and gelatin) as well as endogenous proteins. The apparent Km for S-adenosyl-L-methionine with endogenous proteins as substrates were 30 microM and 4 microM for the cytosolic and BBM enzymes, respectively. These activities were sensitive to S-adenosyl-L-homocysteine, a well known competitor of methyltransferase-catalyzed reactions, but were not affected by the presence of chymostatin and E-64, two protein methylesterase inhibitors. The activity of both cytosolic and BBM PCMT was maximal at pH 7.5, while BBM phospholipid methylation was predominant at pH 10.0. Separation of the = methylated proteins by acidic gel electrophoresis in the presence of the cationic detergent benzyldimethyl-n-hexadecylammonium chloride revealed distinct methyl accepting proteins in the cytosol (14, 17, 21, 27, 31, 48, 61 and 168 kDa) and in the BBM (14, 60, 66, 82, and 105 kDa). Most of the labelling was lost following electrophoresis under moderately alkaline conditions, except for a 21 kDa protein in the cytosol and a 23 kDa protein in the BBM fraction. These results suggest the existence of two distinct PCMT in the kidney cortex: a cytosolic enzyme with low selectivity and affinity, methylating endogenous and exogenous protein substrates, and a high-affinity BBM-associated methylating activity. PMID- 1854791 TI - The effect of ionizing radiation on lipid membranes. PMID- 1854792 TI - Membrane insertion and lateral mobility of synthetic amphiphilic signal peptides in lipid model membranes. AB - Amphiphilic signal sequences with the potential to form alpha-helices with a polar, charged face and an apolar face are common in proteins which are imported into mitochondria, in the PTS permeases of bacteria, and in bacterial rhodopsins. Synthetic peptides of such sequences partition into the surface region of lipid membranes where they can adopt different secondary structures. A finely controlled balance of electrostatic and hydrophobic interactions determines the 'affinity' of amphiphilic signal peptides for lipid membranes, as well as the structure, orientation and depth of penetration of these peptides in lipid bilayer membranes. The ability of an individual peptide to associate with lipid bilayer membranes in several different modes is, most likely, a general feature of amphiphilic signal peptides and is reflected in several common physical properties of their amino acid sequences. PMID- 1854793 TI - Cellular functions of metallo-endoproteinases. PMID- 1854794 TI - Nonparallel transport and mechanisms of secretion. AB - After many years of controversy, it is now clear that at least some cells and tissues that secrete more than one product can vary the composition of the secreted mixture as the result of the differential transport of various substances out of the cells that secrete them. In this article we discuss this phenomenon, non-parallel transport or secretion, and how it has and continues to inform us about how cells release the products they manufacture. We focus on expression of the phenomenon in the secretion of digestive enzymes by the exocrine pancreas, where it has been studied most extensively. PMID- 1854795 TI - Phospholipid fatty acid remodeling in mammalian cells. PMID- 1854796 TI - Feeding rats a diet enriched with saturated fatty acids prevents the inhibitory effects of acute and chronic ethanol exposure on the in vitro uptake of hexoses and lipids. AB - Chow-fed rats were given 15% ethanol in their drinking water for 4 weeks, and then for the next 2 weeks of ethanol exposure they were fed isocaloric semisynthetic diets enriched in either saturated (S) or polyunsaturated (P, linoleic acid) fats. Food intake was lower in ethanol-fed (ETH) than in control (C) rats, but the average body weight gain was similar in ETH and C fed S or P. Intestinal dry weight and the percentage of the intestinal wall comprised of mucosa were more than 2-fold higher in ETH than C fed P, whereas these values were 50% lower in ETH than C fed S. The in vitro jejunal uptake of glucose and galactose was higher in ETH than C fed S, whereas the converse was true when feeding P. These effects were due to differences in the values of the maximal transport rate (Vmax), the Michaelis constant (Km), and the contribution of passive permeation. The relative permeability of the intestine to lipids was unchanged by giving ethanol or by feeding S or P, but the individual rates of uptake of most medium- and long-chain fatty acids and cholesterol were lower in ETH fed P as compared with S. In a second series of studies the acute effect of ethanol exposure was examined: animals were fed S or P for 2 weeks and the intestine was then removed: when 5% ethanol was added directly to the test solutions, there was lower in vitro jejunal and ileal uptake of glucose and higher jejunal uptake of 18:2 when rats were previously fed P, but not in those fed S. In summary; (1) feeding an isocaloric polyunsaturated fatty acid diet has a trophic effect on the intestinal mucosa of animals chronically drinking ethanol; and (2) feeding rats a diet enriched with saturated fatty acids prevents the inhibitory effects of acute and chronic ethanol exposure on the in vitro jejunal uptake of glucose, galactose and lipids observed in animals fed a polyunsaturated diet. Thus, the effect of chronic consumption of ethanol on the active and passive jejunal uptake of nutrients is influenced by the type of lipids in the animal's diet. PMID- 1854797 TI - Increased levels of monohydroxy metabolites of arachidonic acid and linoleic acid in LDL and aorta from atherosclerotic rabbits. AB - Lipid peroxidation results in the formation of peroxy and hydroperoxy metabolites of polyunsaturated fatty acids which can directly or indirectly affect many cellular processes. Lipid hydroperoxides are rapidly metabolized to the corresponding monohydroxy products by various cellular peroxidases. We have measured the amounts of monohydroxy metabolites of linoleic acid (18:2) and arachidonic acid (20:4) in lipids derived from aorta and LDL from rabbits fed a diet enriched in cholesterol and peanut oil for either 8 or 15 weeks. Increased amounts of the 9-hydroxy, and, to a lesser extent, the 13-hydroxy metabolite of 18:2 were observed in aorta and LDL from cholesterol-fed rabbits at both 8 and 15 weeks. The amounts of esterified 11-, 12- and 15-hydroxy metabolites of 20:4 in aortae from cholesterol-fed rabbits were similar to controls after 8 weeks, but about 3-fold higher after 15 weeks. These monohydroxy metabolites of 20:4 were also detected in LDL lipids in cholesterol-fed rabbits. The greater amounts of hydroxy-18:2 in the cholesterol-fed group could be explained by an approx. 2-4 fold increase in 18:2 in aorta and LDL. In contrast, the amounts of 20:4 in aortic lipids were lower in cholesterol-fed rabbits than in controls. Thus, the percentage of esterified 20:4 which had been oxidized to its 11, 12, and 15 hydroxylated metabolites was about 5-times higher in the cholesterol-fed group. Our results would be consistent with the hypothesis that increased amounts of peroxidized 18:2 and 20:4 in lipids could be involved in the development of atherosclerotic lesions in cholesterol-fed rabbits. PMID- 1854798 TI - Enhancing effects of bile salts on the degradation of glycosphingolipids by glycosidases from bacteria of the human fecal flora. AB - Different concentrations of ionic and non-ionic detergents were examined for optimization of the in vitro degradations of intestinal glycosphingolipids by alpha- and beta-glycosidases from human fecal bacteria. In 5 mM Triton X-100 the enzymes hydrolyzed glycosphingolipids with lactoseries type 1 and 2 chains essentially to lactosylceramide (LacCer). In 5 mM sodium di- and trihydroxy bile salts lactosylceramide was degraded to glycosylceramide (GlcCer) in varying extent by enzymes from all five strains. The minimal bile salt concentrations for optimal 1,4-beta-galactosidase activities varied between 1 and 20 mM, i.e., close to or above the critical micellar concentrations (cmc). Dihydroxy bile salts were the most efficient in promoting conversion of LacCer to GlcCer at concentrations below 10 mM and conjugation with a taurine residue did not markedly lower the GlcCer yield. The optimal detergent concentrations for hydrolyses of the p nitrophenyl (pnp) glycosides Gal beta 1-pnp and GalNAc alpha 1-pnp were approximately 0.05 mM for Triton X-100 and 0.5 mM for sodium taurodeoxycholate, i.e., clearly below their reported cmc values. Galabiosylceramide, globotria- and globotetraosylceramides, not degraded in the Triton X-100 micelles, were also resistant to hydrolysis using the sodium bile salts as detergents. In contrast, lactotetraosylceramide and isoglobotriaosylceramide were significantly more degraded by enzymes from a Ruminococcus gnavus strain and gangliotetraosylceramide by enzymes from a Bifidobacterium bifidum and a Bifidobacterium infantis strain using bile salt detergents. All strains but R. gnavus released terminal GalNAc from para-Forssman but not from the globotetraosylceramide or Forssman structures using 5 mM sodium deoxycholate as detergent. GM1 desialylation by two Ruminococcus torques strains and the R. gnavus and B. bifidum strains were enhanced under identical conditions. We conclude that the observed effects on glycosphingolipid hydrolyses reflects variations in the micellar presentation of the substrates. In addition, detergents seem to have a direct stimulating effect on the glycosidases, however at concentrations 10-100-times below the ones optimal for glycolipid degradations. These results with optimized bile salt concentrations, further support our previous observations that these five fecal bacterial strains produce enzymes with selected specificities towards glycosphingolipid core chains of the lactoseries type 1 and 2. PMID- 1854799 TI - Further studies on the purine phosphoribosyltransferase 'burst' velocity reaction. AB - In the assays used to determinate the adenine and hypoxanthine-guanine phosphoribosyltransferases activities from Artemia cysts two phases of velocity are observed in the synthesis of AMP, IMP and GMP: one initial burst and a second, slower, steady-state velocity. Both reaction velocities are divalent cation-dependent and temperature-resistant, as they are detectable at temperatures from 0 to 100 degrees C. Butanol, frequently employed to interrupt the purine phosphoribosyltransferase reactions, does not inhibit the enzyme activities. The 'burst' phase is not detected when the reaction is ended by the addition of EDTA. These data support that the initial velocities of these enzymatic reactions may be due to the accumulation of products formed by the overall reaction, developed subsequent to the controlled reaction period, being the 'burst' a result from the relative resistance of these enzymes to the agents that are often used to stop the reaction, such as heat or butanol. PMID- 1854800 TI - Phospholipase D-catalyzed hydrolysis of phosphatidylcholine occurs with P-O bond cleavage. AB - Mammalian phospholipase D has been implicated in signal-transduction mechanisms, most recently in association with stimuli that enhance phosphatidylcholine (PC) turnover. It was previously unknown whether hydrolysis of PC by phospholipase D proceeds via P-O or C-O bond cleavage. Commercially available phospholipase D isolated from Streptomyces chromofuscus was used to hydrolyse distearoyl phosphatidylcholine (PC) in a detergent-containing buffer consisting of 90% 18O water. The product of hydrolysis, phosphatidic acid (PA), was purified by thin layer chromatography and analyzed using californium-252 plasma desorption mass spectrometry. An increase of two mass units was observed, compared to a distearoyl PA control, consistent with a reaction mechanism involving cleavage of the P-O bond. PMID- 1854801 TI - The catabolism of exogenous lysophosphatidylcholine in isolated perfused rat and guinea pig hearts: a comparative study. AB - Lysophosphatidylcholine (lysoPC) is an arrhythmogenic phospholipid metabolite which accumulates in the ischemic myocardium. Reduced catabolism of lysoPC has been proposed to be one of the biochemical mechanisms responsible for the increase in lysoPC content. In this investigation we compared the microsomal catabolism of exogenous labeled lysoPC in isolated perfused rat and guinea pig hearts. Analysis of the amount of radioactivity in microsomal phosphatidylcholine (PC) and free fatty acid (FFA) was used as an index of the participation in lysoPC clearance by acylation catalyzed by acyl-CoA:lysoPC acyltransferase and deacylation catalyzed by lysophospholipase, respectively. There was no significant difference in the incorporation of radioactivity into rat and guinea pig heart microsomes; however, the patterns of radioactivity in lysoPC metabolites were notably different. Equal participation by deacylation and reacylation was observed in rat microsomes, whereas deacylation was clearly the preferred route for lysoPC clearance in guinea pig microsomes. Modulation of enzyme activity by treatment of the isolated heart with pHMB, a sulfhydryl agent, was used to probe the relationship among acylation, deacylation and the extent of lysoPC clearance. In guinea pig microsomes impairment of lysoPC acylation was not associated with any change in the amount of radioactivity in lysoPC because of a compensatory increase in deacylation. In contrast, impaired deacylation in rat microsomes led to significant elevations in the amount of radioactivity in lysoPC. We conclude, therefore, that in intact perfused rat and guinea pig hearts the relative participation of acylation and deacylation in lysoPC clearance differs. Moreover, we propose that the level of deacylation by lysophospholipase is an important factor in the extent of clearance of lysoPC. PMID- 1854802 TI - The fatty acid composition of placenta in intrauterine growth retardation. AB - To examine the impact of intrauterine growth retardation (IUGR) on essential fatty acids in human placenta, fatty acid composition in total acylglycerol and in the major phosphoglycerides phosphatidylcholine (PC) and phosphatidylethanolamine (PE), of 15 placentas from small for gestational age (SGA) births was compared with that of 7 control placentas. The acylglycerol fatty acid content was similar between the two groups, but the proportion of fatty acids of the linoleic acid series, including arachidonic acid, was significantly lower in SGA placentas. When the fatty acid composition in PC was studied, the reduction in fatty acids of the linoleic acid series was even more striking, and fatty acids of the linolenic acid series was also significantly less in the SGA group. These fatty acid changes in placenta membrane phospholipids can affect the transport of important nutrients to the fetal compartment. The decreased level of arachidonic acid and docosahexanoic acid might also lead to a disturbed formation of fetal thromboxane and prostacyclin. However, cord plasma PC fatty acid patterns were nearly identical in the two groups suggesting that in IUGR, the essential fatty acids will be transported to the fetus at the expense of the placenta. PMID- 1854803 TI - Differential actions of diacyl- and alkylacylglycerols in priming phospholipase A2, 5-lipoxygenase and acetyltransferase activation in human neutrophils. AB - One aspect of human neutrophil (PMN) function during inflammation is formation of platelet-activating factor (PAF), leukotriene B4 (LTB4), and 5 hydroxyeicosatetraenoic acid (5-HETE), but production of these lipid mediators is limited if PMN are directly stimulated with soluble, physiologic agonists. In vitro, PMN activities can be enhanced by the process of primed-stimulation where cells are sequentially treated with non-stimulatory concentrations of different agonists. Many agents that prime PMN also induce production of 1,2-diacyl- and 1 O-alkyl-2-acylglycerols. Therefore, we investigated whether diglycerides were involved in priming PMN for production of lipid mediators. We previously described the ability of the diacylglycerol, 1-oleoyl-2-acetylglycerol (OAG), and its alkylacylglycerol analog, 1-O-octadecenyl-2-acetylglycerol (EAG), to prime phospholipase A2 (PLA2) for subsequent activation by a second stimulus. However, while OAG also primed 5-lipoxygenase activity (LTB4 and 5-HETE production), EAG priming inhibited LTB4 and 5-HETE formation. We now report the effects of diglyceride priming on acetyltransferase activation (PAF formation). PMN, prelabeled with 1-O-[9',10'-3H]hexadecyl-2-lyso-sn-glycero-3-phosphocholine, were primed with OAG or EAG before stimulation. Neither OAG nor EAG induced formation of labeled PAF. Treatment of PMN with the chemotactic peptide, N-formyl-met-leu phe (FMLP), induced low but significant production of PAF; PAF formation doubled in PMN primed with 20 microM OAG before FMLP stimulation while priming with 20 microM EAG more than tripled the level of PAF. Calcium ionophore strongly induced PAF formation; OAG priming before ionophore challenge had no effect but EAG priming further enhanced PAF formation. These results suggests a role for alkylacylglycerols in modulating the production of lipid mediators of inflammation. PMID- 1854804 TI - Inhibition of phosphatidylcholine and phosphatidylethanolamine biosynthesis by cytochalasin B in cultured glioma cells: potential regulation of biosynthesis by Ca(2+)-dependent mechanisms. AB - The major route of phosphatidylcholine (PtdCho) biosynthesis in mammalian cells is the sequence: choline (Cho)----phosphocholine (PCho)----cytidinediphosphate choline (CDP-Cho)----PtdCho. Recently, we have found that intermediates of this pathway are not freely diffusible in cultured rat glioma (C6) cells but are channeled towards PtdCho biosynthesis (George et al. (1989). Biochim. Biophys. Acta. 1004, 283-291). Channeling of intermediates in other mammalian systems is thought to be mediated through adsorption of enzymes to membranes and cytoskeletal elements to form multienzyme complexes. In this study, agents which perturb the structure and function of cytoskeletal elements were tested for effects on phospholipid metabolism in glioma cells. The filament-disrupting agent cytochalasin B (CB), but not other cytochalasins or the microtubule depolymerizer colchicine inhibited PtdCho and phosphatidylethanolamine (PtdEtn) biosynthesis as judged by dose-dependent reduction of labeling from [3H]Cho and [14C]ethanolamine (Etn). 32Pi pulse-labeling indicated that CB selectively decreased PtdCho and PtdEtn biosynthesis without affecting synthesis of other phospholipids. Synthesis of water-soluble intermediates of PtdCho metabolism was unaffected but the conversion of phosphoethanolamine to CDP-ethanolamine was reduced by CB. Effects of CB on phospholipid biosynthesis were not due to inhibition of glucose uptake as shown by experiments with 2-deoxyglucose, glucose-starved cells and other cytochalasins. Experiments with Ca(2+)-EGTA buffers and digitonin-permeabilized cells, and the Ca(2+)-channel blocker verapamil suggest that effects of CB on PtdCho and PtdEtn biosynthesis are due to alteration of intracellular Ca2+. Taken together, these results suggest that CB acts at sites distinct from glucose transport and cellular microfilaments to specifically inhibit PtdCho and PtdEtn biosynthesis by mechanisms dependent on intracellular Ca2+. PMID- 1854806 TI - Oxidation of low-density lipoprotein by copper and iron in phosphate buffer. AB - We examined the effect of phosphate buffer on the iron- and copper-catalyzed peroxidation of low-density lipoprotein (LDL). The incubation of LDL with CuSO4 in 0.15 M NaCl led to the peroxidation of LDL as evidenced by the detection of thiobarbituric acid-reactive substances (TBARS) and lipid hydroperoxides (LPO). The peroxidation of LDL was also observed with FeSO4 and FeCl3 in 0.15 M NaCl, although there was a lag phase with FeCl3. In 10 mM phosphate buffer, the peroxidation of LDL was observed with CuSO4 to an extent similar to that in 0.15 M NaCl. However, the peroxidation induced by incubation with FeSO4 and FeCl3 was significantly inhibited in phosphate buffer. Iron and copper each formed a complex with lipoprotein during incubation with LDL in 0.15 M NaCl. Although no effect on the formation of copper-LDL complex was observed in phosphate buffer, the formation of iron-LDL complex was reduced in the buffer. These observations suggest there are marked differences in the peroxidation of LDL and in the formation of complexes with LDL between iron and copper in phosphate buffer. PMID- 1854805 TI - Effect of pancreatic phospholipase A2 and gastric lipase on the action of pancreatic carboxyl ester lipase against lipid substrates in vitro. AB - Preincubation of a triolein/phospholipid/cholesteryl oleate-emulsion in vitro with either pancreatic phospholipase A2 (PLA2) or gastric lipase (GL) resulted in hydrolysis (measured by pH-stat-titration) of cholesteryl [3H]oleate only after human pancreatic carboxyl ester lipase (CEL) was added to the system. No appreciable hydrolysis was observed when CEL was added alone. Consequently, a concerted action either of PLA2 and CEL or of GL and CEL made the substrate cholesteryl oleate available for hydrolysis by CEL. This was the case when cholesteryl oleate was solubilised in a phospholipid-stabilised triglyceride emulsion, which is the physico-chemical form in which the major part of dietary cholesteryl esters are presented to the gastro-intestinal tract of man. PMID- 1854807 TI - Analysis of non-heme iron in arachidonate 12-lipoxygenase of porcine leukocytes. AB - Arachidonate 12-lipoxygenase of porcine leukocytes, which was purified to homogeneity by immunoaffinity chromatography, was analyzed for iron content by atomic absorption spectrophotometry. The enzyme contained 0.70 +/- 0.09 g atom of iron per mol of enzyme (mean +/- S.D., n = 4). Inorganic iron, which was added to the enzyme solution as an internal standard, was recovered in almost 100% yield. Among various iron chelators tested, only 2,2'-dipyridyl at 1 mM inactivated the enzyme by 87%, but the enzyme was not reactivated by the addition of excess ferrous or ferric iron. PMID- 1854808 TI - An exploration of AIDS education and teaching methods. AB - The purpose of the present research was to examine the relationships between AIDS educational methodologies and learning/retention of medical students. The results suggest that certain teaching methods may be more effective in the development of positive attitudes about caring for persons with AIDS. PMID- 1854809 TI - Sexual behaviour and use of the condom among Ugandan students. AB - HIV infection is widespread in Uganda. Have its university students, the country's leaders of tomorrow, taken appropriate action? A questionnaire was completed by 661 men and 270 women in a one-in-four sample of Makerere University undergraduates (93% response rate). More than 60% of the men and 36% of the women reported at least two sexual partners in the past year. Over 18% of respondents reported at least one episode of sexually transmitted disease in the past year. Most respondents correctly identified the main routes of HIV transmission but risk was also often incorrectly associated with non-penetrative sex. Only a minority saw the condom as an effective preventive method: most saw it as unsafe or an encouragement to promiscuity. Condoms had been used by 35% of men and 24% of women but were currently always used by only 9% of men and 11% of women. The condom was approved of by only one quarter of respondents. Condom use increased with the number of sexual partners but was less likely if the respondent had seen official publicity about the condom. Whilst there were some encouraging signs of behaviour change, opportunities for the spread of HIV continued to abound in this important group. More positive promotion of the condom is urgently required. PMID- 1854810 TI - World Health Organization Global AIDS Statistics. PMID- 1854811 TI - Limited changes in sexual behaviour of heterosexual men and women with multiple partners in The Netherlands. AB - To study changes in sexual behaviour, heterosexuals with multiple sexual partners were recruited through an STD-clinic and asked to return every 4 months for follow-up. Between October 1987 and June 1989, 512 heterosexuals entered the study and 140 men and 200 women had at least one follow-up visit. No changes were found between 3 visits in the kind of sexual techniques practiced. Condom use during vaginal intercourse with commercial partners (prostitutes or clients) was relatively high and remained high, but was low and remained at that level with private partners. Men and women reduced their number of private sexual partners by 50%, but the decline in the number of commercial partners was nonsignificant. Although more information is needed about the underlying social-psychological aspects of behavioural change, it seems necessary to redesign prevention activities to stress the effectiveness of condoms and to encourage condom use especially among heterosexuals with multiple private partners. PMID- 1854812 TI - The formulation and implementation of a national policy on condoms in the context of HIV/AIDS--a review. AB - The AIDS pandemic has brought into sharp focus the role of condoms in preventing the transmission of the human immunodeficiency virus. In the vast majority of countries, the condom prevalence rate is very low and to varying extents socio cultural, infrastructure and logistics, quality control and incorrect usage problems have made it difficult to promote the use of condoms. It is only by developing a national policy on condoms that countries could mobilize within a short span of time all the resources to ensure that condoms are used by those who are at risk of contracting or transmitting HIV. The conditions necessary to develop such a policy and the elements of the policy are described. PMID- 1854813 TI - Condom use in a large cohort of homosexually active men in England and Wales. AB - As part of a prospective study of the seroprevalence of HIV, a cohort of 930 men were interviewed regarding their condom use. Of the 270 respondents that engaged in insertive anal intercourse in the month preceding interview 38.9% always used a condom, 49.6% never used one, and 11.5% sometimes used one. Of the 254 respondents that engaged in receptive anal intercourse in the same time period 42.5% always used a condom, 45.7% never used one, and 11.8% sometimes used one. Compared to other research the proportion of respondents who always use a condom for anal intercourse is relatively high, though use is by no means universal. Condom use is more widespread and consistent with casual rather than regular sexual partners, and it is significantly more common within open rather than monogamous relationships. Out of a wide range of other factors only geographical location (London against outside), marital status, perceived HIV status, number of sexual partners, and how seriously respondents take safer sex are correlated with condom use. PMID- 1854814 TI - The experience of having a positive HIV antibody test. AB - Little is known about the logistics of taking an HIV antibody test and yet knowledge of people's experiences of having a test result is helpful to evolving a sensitive and client oriented service and can provide some guidelines for organisation issues around testing. This paper reports the experiences of 252 gay men who had an HIV test which proved to be positive. The most frequent reasons for people to take a test were perception of personal risk or were related to perceived health problems. Ten per cent of people did not know they had had a test until they were told they were anti HIV positive--lack of knowledge was related mostly to the place where the test was done. Over one third of people said they knew little about the test or its implications before they contacted anyone, over half said they did not receive information at the time of the test and 41% when they were given the result. There were few changes over time in the experience of having a test. PMID- 1854815 TI - Racial differences in social support and mental health in men with HIV infection: a pilot study. AB - The mediating role of social support in the mental health and behaviours of persons coping with life-threatening chronic illness is of potentially great importance in determining the quality of life of persons with HIV infection (PWHs). As part of a biracial pilot study of the ways black and white men manage the stresses of sexually acquired HIV infection, we have examined the relationship between social support and mental health and behaviours. Forty homosexual/bisexual men (20 white and 20 black) attending a Detroit hospital based HIV outpatient clinic were recruited for the study and underwent physical and mental health (HSCL-59 and NIMH DIS interview), behavioural and psychosocial evaluations, and a neuropsychologic screening test battery. The black and white men did not differ in terms of age, education, sexual behaviours, physical or mental health status. However, the black men were less likely to be open about their sexuality to their primary social support network, and to report that their social support was less affirmative than did the white men. When correlations between the six-dimensional social support measures (Wortman & O'Brien, 1987) and HSC-L distress scores were examined, both availability of material social support and affirmation were correlated negatively with distress among the white men but positively among the black men. Similarly, the previously observed positive relationship between perceived adequacy of social support and adoption of safer sexual practices was observed among white but not black participants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1854816 TI - Risk reduction among injecting drug users: changes in the sharing of injecting equipment and in condom use. AB - In an investigation of risk behaviour among injecting drug users in the North West of England, information was obtained concerning the sharing of injecting equipment, respondent's sexual partners and the use of condoms. Between six and nine months after the initial contact, 169 respondents (56%) were contacted again. The emphasis in the second phase of the project was on changes, if any, in risk behaviour that had occurred in the intervening period. Significant reductions were found in sharing, mostly in the more indiscriminate use of others' injecting equipment. No reduction was observed in sharing between injecting partners and little in sharing between close friends. The number of sexual partners had decreased and the use of condoms, although it increased among those involved in temporary relationships, remained low. Impediments to further progress in risk reduction are discussed. PMID- 1854817 TI - Mental health and substance abuse staff: HIV/AIDS knowledge and attitudes. AB - Mental health and substance abuse treatment staff completed a set of measures assessing their attitudes, knowledge, and beliefs concerning AIDS. Results indicated that while most staff were aware of basic information about the disease, approximately one-third were not aware of the neuropsychological and psycho-behavioural concomitants of the disorder. Those surveyed were aware of the main transmission routes, but overgeneralized their concern to casual contact. Most staff indicated willingness to work with HIV-infected individuals, although 29% stated they would try to avoid working with them. Interestingly, mental health staff expressed greater hesitancy than substance abuse staff. These and other results are interpreted to suggest that some desensitization of concern may have already occurred among those who have worked with HIV-positive clients. Individuals who had worked with an HIV-positive client had greater knowledge, less discomfort, and were less likely to want to avoid those who are HIV positive. Questions attempting to identify sources of discomfort in working with AIDS or HIV-positive clients suggested that fear of contagion may be the primary concern, followed by discomfort of working with the terminally ill, and then discomfort with IV drug users and homosexuals. The implications of these results for continuing education activities and staff readiness are discussed. PMID- 1854818 TI - [The effect of low concentrations of adaptogen solutions on the functional activity of murine bone marrow cells in vitro]. AB - Influence of water solutions of chemically pure adaptogens--a synthetic analog of Rhodiola rosea extract phenol combination (SAR) and Dibazol on the functional activity of mice hemopoietic cells in vitro was studied. A clear periodical character of drugs effects manifestation with a tendency to the stimulating activity domination was revealed. A reliable stimulation of clonogenic activity was in correlation with 4 x 10(-11) and 4 x 10(-15) adaptogens molecules in SAR and Dibazol solutions per 1 blood marrow cell. This phenomenon is suggested to be connected with the solvent (water) molecules changes and the formation of structures, keeping the information of adaptogenes with possible translation of the latter during the process of consistent dissolution of the solvent. PMID- 1854819 TI - [Computer analysis of the dynamics of two tumor foci with respect to circulating immune cells]. AB - A mathematical model of the bilocal immunogenic tumors was analysed by a computer. An increase of the intensity or/and growth of asymmetry in cytotoxic cells migration between two tumor centres could lead to bifurcations in the system. This approach allows interpretation of a number of paradoxes in the interrelations between the original tumor and metastases. PMID- 1854820 TI - [A method of computing the degree of periodic arrangement of leukemia cells in suspension]. PMID- 1854821 TI - [A magnetic field arising upon passage of an electrical current through the human arm]. AB - Asymmetry of the magnetic field density along the arm perimeter under electric pulse with the usage of various electrodes was investigated. This research helped to prove the existence of special passageways in the human body (besides the nervous ones) which transmit the electric pulse. It was revealed that induction of electrodes into acupuncture points determined the distribution of power density along the arm section. In this case it depends upon the points used. PMID- 1854822 TI - [Determination of the turbidity temperature of solutions of the nonionogenic surface-active agent LF-57 after the action on urinary calculi in uric acid]. AB - Non-ionogenic surfactant LF-57 contributes solving of urinary calculi from uric acid and is a component of the drug Pharmalit for curing kidney-stone disease. Turbidity temperature was determined of the solution LF-57-78, 1C, and in the presence of uric acid--80.2C. PMID- 1854823 TI - [The effect of nitrogen and oxygen on triboluminescence generated by blood]. AB - The spectrum of triboluminescence by dried blood on a TPA-2 triboluminometer was shown to display four bands of emission with maximum levels at 262, 321, 422 and 649 nm, which are due to the processes of gas discharge in nitrogen and oxygen and to the luminescence of polytetrafluorochlorethylene probe, triboelectriating the samples under study. The intensity of triboluminescence of dried blood and its components depends on the value of pO2 in the liquid phase of the samples. PMID- 1854824 TI - [Magnetohydrodynamic effects during blood movement]. AB - Theoretical investigations of magnetohydrodynamic (MHD) effects in flowing blood are briefly reviewed in their formal and physiological aspects. It is shown that the great part of published works contain serious errors, as well as groundless practical propositions without any satisfactory explanation. PMID- 1854825 TI - [A quantitative assessment of the "tendon" action of two-joint muscles]. AB - Two-joint muscles are able to transmit mechanical energy between the links of the body having no common joint ("tendon action" of the muscles). It is proposed to calculate difference between control moment power in a joint and the sum of powers developed by all muscles serving this joint in order to determine the direction and rate of mechanical energy transfer through the two-joint muscles. It was shown that in the shock-absorbing phase of support in running two-joint muscles the energy transfers from distal to proximal links (from foot to thigh, and from shank to pelvis), in take-off phase-from proximal links to distal ones (from pelvis to shank, and from thigh to foot). PMID- 1854826 TI - [Ca+-dependent efflux of K+ from erythrocytes, induced by an oxidative process]. AB - Effects of inhibitors of energetic processes, antioxidants and SH-reagents on Ca(2+)-dependent K+ efflux from human red blood cells induced by oxidizing agents, electron donor system ascorbate + phenazine methosulphate (PMS) and Na periodate were investigated. We concluded that different regulatory mechanisms of K+ efflux from cells existed. In contract to periodate effect, Ca(2+)-dependent K+ channel activated by ascorbate + PMS is functionally connected with the membrane redox components. PMID- 1854827 TI - [Effect of pH and preparation method on thermal denaturation of thymus DNA in salt-free solutions]. AB - Thermal denaturation of calf thymus DNA was studied by scanning microcalorimetry. It has been shown that long dialysis of DNA against water causes a sharp decrease of DNA thermal stability due to biopolymer protonation. The literature data on the properties of DNA salt-free solutions obtained by dialysis are discussed. PMID- 1854828 TI - [Features of the interaction of antitumor mitoxantrone compounds with sarcoma 45 tumor DNA]. AB - The interaction of antitumoral drug mitoxantrone with DNA of the tumor sarcoma 45 and healthy animals liver has been investigated according to the character of changes on the absorption spectra at binding at 30 degrees C and 0.11 M NaCl. The investigation shows that the interaction of mitoxantrone with DNA of sarcoma 45 differs from that with DNA of healthy animals liver. The calculations show that the saturation stoichiometry by both DNA is one mitoxantrone molecule per 2.5 base pairs with the binding constant k = 4 x 10(5) M-1 (for binding mitoxantrone with liver DNA) and k = 3 x 10(6) M-1 (with tumor DNA). Possible reason of such a difference is discussed on the basis of structural peculiarities of tumor DNA. PMID- 1854830 TI - [The role of water in cell function]. PMID- 1854829 TI - [Number of cooperative regions (energy domains) in the pepsin molecule depends on the pH of the medium]. AB - Ethanol and pH influence on the number and dimensions of cooperative regions in pepsin molecule was studied by scanning microcalorimetry. It is shown that ethanol solution causes a decrease of temperature of protein denaturation but does not influence the number of energetic domains. While changing pH from 6.7 to 2.0 the number of thermodynamic cooperative units (defined as the ratio delta Hcal/delta Heff) decreases from four to two. This process, as shown by CD technique, is followed by changes neither in the secondary structure, nor in the local environment of aromatic amino acids. A conclusion is made that the distinctions in cooperative characteristics of the protein globule at different pH are determined by electrostatic interactions of separate parts of the molecule. PMID- 1854831 TI - [Design of a mathematical model of the formation of erythrocyte shape as an autowave process]. AB - The phenomenological model of T. Teorell's "biomembrane generator" underlies the mathematical model of erythrocyte forms as an autowave process. For a distributed system the model is formulated as a differential equation of the second order in partial derivatives with a small parameter. It is stated that a substantial thing in the model is the presence of mass-transfer through a pore membrane determined by its electrostatic and hydrostatic permeabilities, as well as the fact that mass-transfer through the membrane results in a non-uniform distribution of the liquid current through it. It is suggested that as a consequence of this process there appears mechanical instability of the spherical membrane, which is the cause of the autowave process. Due to the membrane elasticity this process can be compared with the movement of "tank caterpillar". PMID- 1854832 TI - [Asymptotic solution of the model of the erythrocyte shape as an autowave process]. AB - An asymptotic solution was plotted for a model of erythrocyte forms assuming that the biomembrane is anisotropic and of "small" thickness. This leads to small non linearity and low diffusion, therefore the solution is unrelaxational. The model was investigated qualitatively assuming that the liquid current directed inside the spheric membrane induces its "distension", while that directed outside-its "crumpling". In the spherical system of coordinates the lines of solution level at theta = const are circumferences, while at phi-const-trochoids (Pascal coil, for example). Trochoids rotation areas show stomacyte and discocyte forms. Several hypotheses based on the analysis performed are advanced. PMID- 1854833 TI - Retroviral oncogenes: interrelationships between neoplastic transformation and cell differentiation. PMID- 1854834 TI - Current status of protein methylation in carcinogenesis. PMID- 1854835 TI - [Endocarditis caused cy Erysipelothrix rhusiopathiae. Study of 2 cases and review of the literature]. AB - Endocarditis produced by E. rhusiopathiae is a uncommon disease. Most of the infected persons (90%) work in environments with frequent exposure to E. rhusiopathiae (butchers, fisherman). Although the clinical picture of endocarditis produced by E. rhusiopathiae is indistinguishable from other forms of subacute endocarditis, this infection has a mortality rate of 40% and a high morbidity. Microbiological diagnosis should consider the possibility of making a mistake considering that isolation of a gram-positive bacillus may represent contamination by an agent without clinical relevance. Treatment with penicillin G during 4 weeks is commonly sufficient to cure the disease. PMID- 1854836 TI - [Molecular mechanisms of invasion and virulence in strains of the mesophilic aeromonas group isolated from human beings]. PMID- 1854837 TI - [Ticks and Lyme disease]. PMID- 1854838 TI - [Suppurative lumbar swelling]. PMID- 1854840 TI - [Bilateral plantar lesions]. PMID- 1854839 TI - [Fever, pain in the right leg and an abdominal mass]. PMID- 1854841 TI - [Calcified pulmonary lesions]. PMID- 1854842 TI - [Outbreak of borreliosis. Apropos of 7 cases]. PMID- 1854843 TI - [Infection caused by Borrelia burgdorferi in Extremadura]. PMID- 1854844 TI - [Study of cross reactions using serological techniques between Borrelia burgdorferi and Treponema pallidum]. PMID- 1854845 TI - [Isolation of Salmonella spp. from feces. Comparison of Rappaport-Vassiliadis media with selenite and tetrathionate basal media]. PMID- 1854846 TI - [Ampicillin resistance in Salmonella]. PMID- 1854847 TI - [Infection of a subcutaneous venous reservoir in a patient wtih AIDS]. PMID- 1854848 TI - [Application of various epidemiological markers during an outbreak of food poisoning caused by Salmonella]. PMID- 1854849 TI - [IgA glomerulonephritis associated with pneumonia caused by Mycoplasma pneumonia]. PMID- 1854850 TI - [Aphthosis major treated with thalidomide in a patient with AIDS]. PMID- 1854851 TI - [Autochthonous amebic liver abscess in a heterosexual man with human immunodeficiency virus infection]. PMID- 1854852 TI - [Vancomycin resistance in Gram-positive bacteria]. PMID- 1854853 TI - [Selective digestive decontamination. An entity to be defined]. PMID- 1854854 TI - [Yield from studying the contacts of patients with tuberculosis]. AB - Between march '88 and august '89 a total number of 437 contacts (CT) with 69 patients with tuberculosis were analyzed. According to the bacteriological status of the index case the observations were distributed into: Group I (197) CT with patients with positive sputum AFB stain test; Group II (24) CT with cases with positive sputum culture but negative AFB stain; and Group III (216) CT with cases with histologic diagnosis or cases in children. Following identical criteria and according to the bacteriologic situation of the Source case, we grouped the contacts on groups A (246), B (17), and C (174). A clinical history, thorax radiography, and tuberculin test with 2 UT of PPD-RT 23 were performed in all CT cases. Tuberculin reaction was equal or greater than 6 mm in 45% (88/197), 25% (6/24), and 36% (77/216) of groups I, II, and III respectively. This reaction was also positive in 49% (121/246), 23% (4/17), and 26% (46/174) of groups A, B, and C respectively. Sixteen new cases of tuberculosis were discovered among which we identified 5 new source cases. A second tuberculin test was performed in 44% (116/266) of CT with a previous negative test, and in this population we observed 16 conversions. It is demonstrated: 1) a high yield in the detection of infection/tuberculous disease; 2) the analysis of CT in group A provided the highest index of tuberculous infection, and 3) revision of CT of groups II and III provided most of the new cases of disease as well as the identification of 5 new source cases. PMID- 1854855 TI - [Brain lesions in patients with acquired immunodeficiency syndrome]. AB - During a period of 3 years 14 patients with AIDS and CNS focal lesions documented by CT scan were evaluated. All patients received empirical treatment against Toxoplasma. The aim of the study was to determine the prevalence of the different etiologies of the neurologic lesions as well as to evaluate the usefulness of routine cerebral biopsy before establishing empiric antitoxoplasma treatment in a population of AIDS patients with a high incidence of drug addiction. Eleven patients developed histologic and clinical criteria of cerebral toxoplasmosis, one patient presented progressive multifocal leukoencephalopathy, and in the remaining two patients the etiologic diagnosis could not be established. Only one patient presented multiple etiologic lesions and in no cases the presence of mycobacteria or fungi could be demonstrated in the cerebral tissue. The overall percentage of responses to the empiric antitoxoplasma treatment was 42%. This percentage increased to 54% if patients with coma were not included in the analysis. Cumulated mortality of the entire group was 78.5%. It is concluded: 1) the predominance of Toxoplasma gondii as a cause of cerebral lesions in our AIDS population; 2) the acceptable percentage of response to empiric antitoxoplasma treatment in non-comatose patients, and 3) the high overall mortality rate in these patients. It is therefore suggested that routine cerebral biopsies will not be justified as initial diagnostic approach in HIV positive patients with focal CNS lesions. PMID- 1854856 TI - [16 cases of infection by Cryptococcosis neoformans in patients with AIDS]. AB - Sixteen patients with AIDS (6% of the total AIDS patients) who had infection by Cryptococcus neoformans were studied. Most of these patients (94%) had cryptococcal meningitis. Only 50% of the cases showed clinical manifestations of neurological involvement. Blood cultures and antigen level measurement were the diagnostic techniques with best results due to their high percentage of positivity. Sixty nine percent of patients survived the acute phase of the infection and only 3 of those who died in this period showed evidence of active infection patients by the fungus. PMID- 1854857 TI - [Evaluation of the Vitek system in the identification and biotyping of Streptococcus agalactiae]. AB - Using the Vitek card for identification of gram-positive agents, 244 strains of Streptococcus agalactiae were studied. Twenty five out of these strains were studied during 3 consecutive days. The study also involved 25 pairs of maternal and neonatal strains. The system gave correct identification of only 52 out of 244 strains of S. agalactiae. Due to the low reproducibility of the system it is suggested that the bionumbers used in the codification of a microorganism should be avoided. PMID- 1854858 TI - Psychophysics of muscle tension in psychiatric inpatients. AB - Twelve psychiatric inpatients and 16 control subjects each took part in a psychophysics experiment in which the method of production was used to study the perception of tension in the frontalis and forearm extensor muscles. Subjects tensed each muscle between 0% and 50% maximum effort, with 25% effort repeated every third trial, and used as a reference stimulus. Patients showed significantly lower correlations between frontalis EMG and percent effort than the control subjects, but no between-groups differences were found for forearm. Correlations were higher for differences between successive trials than for absolute values because of apparent baseline shifts in perception and/or production of muscle tension. The performance among the patients was not correlated with severity of psychiatric symptoms, antipsychotic medication, abnormal movements, or parkinsonian symptoms, although the n was small. Analysis of the regression of EMG on percent effort revealed approximately equal descriptive strength for three functions: a linear relationship, Stevens' power function, and Fechner's law. The implications of these findings for self regulation therapies are discussed. PMID- 1854859 TI - Muscular response to the therapist and symptomatic improvement during biofeedback for tension headache. AB - The relationship between muscular response to the therapist's presence and symptomatic improvement was studied during biofeedback. Thirty-two patients suffering from tension headaches received muscular biofeedback training of six sessions plus a follow-up session two months later. Patients' electro-myographic frontal response was measured prior to treatment both with and without the therapist present. A relationship was found between symptomatic improvement at follow-up and muscular response to the therapist's presence before treatment: patients showing a decrease of at least 10% in muscular tension response to the presence of their future therapist improved more regarding headache intensity than the patients showing increase or smaller variation of their EMG. A significant correlation of .59 was found between the frontal EMG response to therapist presence during the evaluation session and headache improvement at follow-up. The results suggest that the decrease of muscular tension during the first contact with the therapist could be an indicator of good prognosis, possibly because of an immediate positive therapeutic relationship and/or favorable expectancies concerning future benefit of treatment. PMID- 1854860 TI - An analogue study of the initial carryover effects of meditation, hypnosis, and relaxation using native college students. AB - An analogue study involving two experiments was conducted to test the initial carryover effects of hypnosis, meditation, and relaxation upon self-reports of awareness. In the first experiment, concentrative meditators reported fewer nonsensorial events than controls. In the second experiment, concentrative meditators again reported fewer nonsensorial events, but covariate analysis and pretest/posttest comparisons revealed that it was the controls who had changed, increasing their nonsensorial reports. In addition, the relaxation group increased its reports of somatic awareness. Results were discussed in terms of the effects of performance demands and the possibility that meditation and hypnosis might be able to disinhibit awareness processes otherwise inhibited by normal daily routines. PMID- 1854861 TI - EMG muscle scanning: comparison to attached surface electrodes. AB - Electromyographic (EMG) muscle scanning measures brief samples of integrated muscle action potentials from individual muscles using a hand-held scanner with post-style electrodes. This "scanning" technique is widely used by biofeedback practitioners to quickly assess muscle activity in the diagnosis of musculoskeletal disorders. In an effort to compare muscle scanning with the established technique using attached surface electrodes, ten healthy subjects (25 35 years old) were scanned using 2-second sampling at five bilateral muscle sites while simultaneously monitoring the same sites with surface electrodes. This was repeated using 10-second scanning samplings. Pearson's product-moment correlations between scanning for 2 seconds and prolonged surface recording at all sites were 0.54-0.89. Scanning for 10 seconds improved the correlations to 0.68-0.91. EMG scanning for 2 seconds compares favorably with attached surface electrode recording. Comparisons are further improved by 10-second scans. PMID- 1854862 TI - A preliminary investigation of prediction of mean arterial pressure after self regulatory treatments. AB - This study investigated the ability of pretreatment variables from three different domains (social-demographic, psychological, and psychophysiological) to predict posttreatment mean arterial pressure (MAP) for 59 unmedicated males with mild hypertension who were participating in a cross-cultural (USA-USSR) comparison of autogenic training and thermal biofeedback to a self-relaxation control. The overall multiple regression equation consisted of two variables and indicated that higher diastolic blood pressures during a cold pressor task were predictive of greater MAP reductions while higher scores on the Irritability subscale of the Buss-Durkee Hostility Scale were predictive of less MAP reductions. Suggestions for future research in this area are provided. PMID- 1854863 TI - Negative side effects of self-regulation training: relaxation and the role of the professional in service delivery. AB - Procedures used for relaxation training can resolve or precipitate dysfunction in patients undergoing self-regulation treatments. The present article discusses the role of the clinician in administering relaxation training via thermal biofeedback and coping with unforeseen negative effects of treatment. A case illustration involving the biobehavioral treatment of chest pain is presented and discussed to remind the reader of the significance of the therapist's role in helping tailor treatment programs to unique responses of the individual patient. The case highlights the value of thorough case management and clinical formulation in the successful resolution of relaxation-induced leg pain. PMID- 1854865 TI - The industrialization of the hospitals and the unhappiness of the physicians. PMID- 1854864 TI - Physiological mechanisms of temperature biofeedback. AB - Research on the physiological mechanisms of finger temperature biofeedback with normal subjects and Raynaud's disease patients is reviewed. Studies conducted in the author's laboratory have shown that feedback-induced vasodilation is mediated through a non-neural, beta-adrenergic mechanism rather than through reductions in sympathetic nervous system activation. In contrast, feedback-induced vasoconstriction is mediated through the traditional, sympathetic nervous pathway. When used with primary Raynaud's disease patients, feedback-induced vasodilation has achieved reductions in reported symptom frequency ranging from 66% to 92% in controlled investigations. Future research directions are discussed. PMID- 1854866 TI - Host defense mechanisms in the peritoneal cavity of continuous ambulatory peritoneal dialysis patients. 2. Humoral defenses. AB - This is the second of a 2-part series reviewing host defense mechanisms of the peritoneal cavity of continuous ambulatory peritoneal dialysis (CAPD) patients. This article discusses humoral aspects of host defenses and accompanies the first article that focused upon cellular defenses. The purpose of this review is to provide a critical analysis of studies that have investigated the importance of peritoneal humoral immunity of CAPD patients in the pathogenesis of peritonitis. Specific attention is given to how CAPD alters normal humoral defenses of the peritoneal cavity and the clinical significance of such alterations. PMID- 1854868 TI - Reduced risk for peritonitis in CAPD with the use of a UV connector box. AB - A common route for peritoneal infection is the bag transfer connecting site. To investigate possible reduction of such transfer infections with the use of a bag transfer set (UV-XD, Travenol, Baxter, Minneapolis), this study sampled patients using a transfer set with or without UV light sterilization. Calculations excluded peritonitis due to penetrating tunnel infection or defective peritoneal dialysis bag (4 episodes in 2 patients). The study included 51 patients with a median age of 62 years (range 25-81). Five were switched from manual connection (Travenol, Type II) to UV-XD, and each suffered from at least 2 peritonitis episodes during 9-24.5 months prior to the change to UV-XD. In this patient group, the incidence of peritonitis fell significantly from 1 peritonitis/4 to 1/21 months. The bag transfer set was used without UV light in 35 patients for a total of 178 months, producing an incidence of 1 episode/7.7 treatment months. These patients had significantly more peritonitis than 35 patients who used the UV light for a total of 416 months (1 episode/21 months). In 19 patients who used both techniques, there was less risk for peritonitis when UV light was used (p = 0.001). We conclude that the UV-XD device is simple to handle and may reduce the incidence of peritonitis, especially if the box is used in tandem with UV light sterilization. PMID- 1854867 TI - A multicenter, selection-adjusted comparison of patient and technique survivals on CAPD and hemodialysis. AB - Four hundred and eighty CAPD and 373 HD patients started regular dialysis treatment between 1981 and 1987 in 6 dialysis centers. The CAPD patients were 6 years older, on average, than the HD patients and had more complicating conditions (43.3% with 3 or more coexisting risk factors versus 28.9% with coexisting complications). The 7-year patient survival rate was not significantly different. Cox's proportional hazards regression showed that age, cardiovascular disease, cerebrovascular disease, peripheral vascular disease, diabetes, malignancy and multisystem disease had significant adverse effects on patient survival. After correcting for the influence of these factors, no significant differences in patient survival were seen. However, after 53.5 years of age, the increase in the risk of death was significantly higher in HD than in CAPD patients. Technique survival was significantly different in the 6 centers and was better for HD than for CAPD. There was no statistically significant difference between CAPD and HD technique survival when peritonitis was eliminated as a cause of failure. Based on this 7 year analysis, CAPD would appear to be an excellent alternative to HD. PMID- 1854869 TI - Design and testing of the Baxter Integrated Disconnect Systems (IDS). AB - This paper describes the result of a miltidisciplinary approach to the design and evaluation of a new CAPD disconnect system: the Baxter Integrated Disconnect System (IDS). This system consists of a bag full of fresh Dianeal, an empty bag for the drainage of spent dialysate and tubings connecting the 2 in a Y fashion. With this system, the patient makes only one connection. The system is disposable. The major property that makes this unique is that all components are preassembled, and the whole system is steam-sterilized as 1 unit. In general, similar systems use different sterilization methods for the various components of the system. Those components are then assembled, under clean conditions by the manufacturer, without final sterilization of the unit. Assembly of the components is sometimes left to the patient. The concept of IDS, therefore, is unique and warrants lower rates of contamination. This system has been tested on patients for a total observation period of 765 patient months, and has proven to be simple, safe and effective. It yields a 63% probability of peritonitis-free patients at 24 months. PMID- 1854870 TI - Comparative study between intact PTH and fragments of PTH in patients on hemodialysis and CAPD. AB - Twenty-nine patients on hemodialysis (HD) and 29 patients on continuous ambulatory peritoneal dialysis (CAPD) were studied. Serum calcium and phosphorous levels were similar in the 2 groups. Serum parathyroid hormone (PTH) levels were determined by 4 different methods. Mid-molecule PTH levels were higher in HD (1099.5 +/- 876.8 pmol/L) than in CAPD patients (541.0 +/- 138.8 pmol/L), p less than 0.001, while intact PTH levels were similar. The ratio MM-PTH/Intact PTH was higher in HD (55.2 +/- 29.0) than in CAPD patients (39.0 +/- 20.0), where p less than 0.01. In patients with similar C-PTH, those on CAPD had higher levels of intact PTH (46.0 +/- 27.0 pmol/L) than those in HD (29.3 +/- 29.0 pmol/L), p less than 0.01. The ratio C-PTH/intact PTH was higher in HD (104.9 +/- 39.6) than in CAPD patients (59.3 +/- 32.3), p less than 0.001. The Peritoneal Saturation Index (PSI) of MM-PTH was 23.4 +/- 12%, and it showed a hyperbolic correlation in respect to MM-PTH serum levels. We concluded that CAPD can modify the plasma C PTH and MM-PTH serum levels by peritoneal losses of these fragments. PMID- 1854871 TI - Influence of dialysate exchange on cardiac left ventricular function in children treated with CAPD. AB - The influence of peritoneal dialysate exchange on the ventricular function in 11 children on continuous ambulatory peritoneal dialysis (CAPD) therapy was studied before and after instillation dialysate. Systolic blood pressure, pulse rate, and echocardiographical data (shortening fraction and pre-ejection period/left ventricle ejection time-ratio) were obtained before and after instillation. There were no differences present with respect to the measured parameters after the abdomen was filled. It is concluded that in children treated with CAPD the exchange of normal volumes of dialysate has no influence on the function of the left ventricle. PMID- 1854872 TI - Factors affecting lymphatic absorption in Chinese patients on continuous ambulatory peritoneal dialysis (CAPD). AB - The pathways and physiology of lymph absorption (LA) from the peritoneal cavity are well documented; however, much uncertainty still exists as to the various clinical and demographic factors affecting LA. We studied LA measured by the albumin instillation method, in adult Chinese CAPD patients, and showed that it was independent of age, sex, body surface area, duration of dialysis, intrinsic renal disease, use of intraperitoneal drugs (heparin/antibiotics/deferroxamine) and frequency of past bacterial peritonitis. High lymph absorbers had a relatively higher transcapillary cumulative ultrafiltration than low lymph absorbers. An enhanced LA was associated with a high initial intraperitoneal volume. Assessment of diaphragmatic strength by the decrement in vital capacity on changing from an erect to a supine position failed to distinguish patients with high and low LA. PMID- 1854873 TI - Vestibular toxicity due to gentamicin in peritoneal dialysis patients. AB - Gentamicin is well known to be a cause of vestibular toxicity. Despite this, gentamicin is often used to treat peritonitis and exit-site infections in peritoneal dialysis patients because of the ease of intraperitoneal administration and the broad coverage of aerobic Gram-negative bacilli, including Pseudomonas aeruginosa. We report 4 cases of severe vestibular toxicity occurring in peritoneal dialysis patients treated with gentamicin. They were all treated as outpatients for peritonitis or an exit-site infection while on continuous ambulatory peritoneal dialysis (CAPD) or continuous cyclic peritoneal dialysis (CCPD). The drug was administered to 3 patients in each peritoneal exchange (5 mg/L) after a loading dose. A fourth patient was given 1 mg/kg of intraperitoneal gentamicin every other day. The mean length of treatment was 21 days. Levels were not used to adjust the doses. All developed severe vertigo from which there was incomplete or no recovery. We suggest that gentamicin and the other aminoglycosides should be used in peritoneal dialysis patients only when there is no suitable alternative antibiotic. When gentamicin is administered, levels should be carefully followed. Studies should be performed in peritoneal dialysis patients on the feasibility of dosing gentamicin intermittently, which may be less toxic than continuous intraperitoneal administration. PMID- 1854874 TI - Is intraperitoneal tobramycin ototoxic in CAPD patients? AB - In 40 CAPD patients treated for peritonitis, the authors did a prospective study of ototoxic effects of intraperitoneal tobramycin. They evaluated cochlear function in pure-tone threshold audiograms over a range of frequencies from 250 10,000 Hz, in the speech-reception threshold test and in the speech discrimination test. These tests were performed within 48 hours of initiation of tobramycin treatment and within 2 or 3 weeks of the drug's discontinuation. With the aminoglycoside doses used in this study, no statistical difference between the mean baseline and mean follow-up hearing levels was seen in these 40 patients. However, according to the standard criteria of ototoxicity, the hearing in 10 of 40 patients (25%) deteriorated after tobramycin, while it improved in seven patients (17.5%). In the remaining 23 (57.5%), hearing remained stable. With respect to the risk factors for ototoxicity such as advanced age, increased duration of treatment, elevated plasma aminoglycoside levels, concomitant treatment with other ototoxic drugs, pre-existing hearing loss, renal dysfunction and hyperthermia, no statistically significant difference was demonstrated between the patients with deteriorated, stable or improved hearing. The results of this study do not confirm that tobramycin given intraperitoneally to CAPD patients produces auditory toxicity. The hearing deterioration observed in 10 patients may be due to synergistic factors. The improvement observed in 7 patients could not be explained. PMID- 1854875 TI - The utility of a structured evaluation of elderly patients for continuous peritoneal dialysis. AB - The elderly comprise an increasing proportion of chronic dialysis patients. Recruiting them for continuous peritoneal dialysis (CPD) would help CPD programs maintain a patient population. We retrospectively studied the ability of a prospective evaluation to predict success with CPD in elderly (age greater than 60 years) patients. PD nurses and a renal social worker assigned scores in 10 categories, which were then averaged to obtain an over-all evaluation score. Scores were from 1-5 with 1 = good, 5 = poor, and 3 = average. Thirty-four elderly patients began CPD during the study period. Evaluation scores were available for 28 of these patients before they began dialysis. Evaluation scores less than 3 predicted success with CPD (2.2 +/- 0.2 versus 3.2 +/- 0.4 in patients transferring to hemodialysis, p less than 0.02). Patient motivation and preference were the categories that predicted success with CPD. Elderly patients were more likely than younger patients (those less than 60 years of age) to decline CPD for social reasons (46% versus 4% respectively, p less than 0.001). Elderly patients required more CPD training time than young patients (4.9 +/- 0.7 days versus 3.3 +/- 0.8 days respectively, p less than 0.01). We conclude that a prospective assessment of elderly patients can predict success with CPD and provide information important to individual structuring of CPD training and follow-up. PMID- 1854876 TI - Sclerosing peritonitis complicating prolonged use of chlorhexidine in alcohol in the connection procedure for continuous ambulatory peritoneal dialysis. AB - Sclerosing peritonitis (SP) is an uncommon but serious complication of CAPD with various suggested etiologies. We have documented 14 cases of SP in 18 patients who had used chlorhexidine in alcohol (ChA) in the connection procedure for CAPD. Thirteen died. Nine of the 14 patients had been transferred to hemodialysis or renal transplantation, yet all still developed symptoms of SP within a few months after transfer - even the 5 who were originally asymptomatic. The main symptoms of SP were peritoneal ultrafiltration failure, exudative bloody ascites and intestinal obstruction. They presented at around 5 years (30-80 months) after commencement of CAPD. Most deaths were related to intestinal obstruction. Four other patients with a comparable duration of ChA exposure were continued on CAPD with the Travenol Spike System (TSS), without further exposure to ChA. They were all asymptomatic of SP after 9-12 months. Comparing the 2 groups of asymptomatic patients, those transferred to TSS had a much better outcome after 9 months than those transferred to HD or renal transplantation (P = 0.0476). We suggest that ChA is the main cause of SP in our patients and that continuing CAPD without further exposure to ChA is a better alternative than stopping CAPD to prevent the progression of SP. PMID- 1854877 TI - Strategies for improving dialysis decision making. AB - It is important that every professional involved with guiding ESRD patients through the maze of dialysis decision making critically analyze his or her own behaviors, possible biases and thought processes influencing discussions with patients. Health care professionals need to continue to strive to improve their skills for assuring optimal assistance to their patients in making decisions about the best types of treatments for them. In this era of evermore challenging patients and technologies, the skills for informing patients and assisting them with effective decision making about issues such as medical management, dialysis, transplantation or treatment termination are vital for assuring quality care. PMID- 1854878 TI - MTC of inulin from blood to peritoneum and from peritoneum to blood in CAPD patients. PMID- 1854879 TI - Pasteurella multocida peritonitis in CAPD: beware of the cats. PMID- 1854880 TI - Cure of persistent Pseudomonas peritonitis after prolonged antibiotic administration in CAPD patients. PMID- 1854881 TI - Literature. April-June 1991. PMID- 1854883 TI - Transforming genes and chromosome aberrations in therapy-related leukemia and myelodysplastic syndrome. AB - The presence of activated transforming genes was investigated in four patients with therapy-related leukemia and in three with therapy-related myelodysplastic syndrome. DNA of bone marrow cells from six of the patients exhibited transforming activity in the tumorigenicity assay. Five of the six patients who were positive in the tumorigenicity assay contained activated N-ras oncogenes, and three contained activated K-ras oncogenes. Thus, concurrent activation of N ras and K-ras oncogenes was observed in two patients. In vitro DNA amplification followed by oligonucleotide dot-blot analysis was used to investigate mutations in codons 12, 13, and 61 of the N-ras and K-ras oncogenes. Two patients exhibited an N-ras mutation, substituting aspartic acid (GAT) for glycine (GGT), and three patients exhibited an N-ras codon 13 mutation, substituting valine (GTT) for glycine. Two patients exhibited K-ras codon 12 mutations, substituting aspartic acid (GAT) or cysteine (TGT) for glycine (GGT), respectively, and one case exhibited a K-ras codon 61 mutation, substituting lysine (AAA) for glutamic acid (CAA). Cytogenetic analysis revealed that loss of chromosome 7 was frequent (four patients: 57%). Our data indicate that activation of N-ras and K-ras genes, as well as loss of heterozygosity for specific alleles on chromosome 7, plays a more important role in the leukemogenesis of both therapy-related leukemia and myelodysplastic syndrome. PMID- 1854882 TI - Interleukin-6 in clinical medicine. AB - This article covers the basic biological functions of interleukin-6 (IL-6) in man. Three major topics are addressed more closely: the involvement of IL-6 in various disease states, particularly those of hematopoietic origin; the diagnostic usefulness of IL-6 measurements in biological fluids; the possible use of IL-6, IL-6 antagonists or IL-6 derivatives as therapeutic means. PMID- 1854884 TI - Further evidence for the molecular heterogeneity of chronic myeloid leukemia. AB - Cytogenetic and molecular techniques were performed on samples obtained from 29 patients with chronic myelocytic leukemia (CML); 27 were in the chronic phase and two were in blast crisis. A further five cases were also analyzed, two with atypical CML (aCML), one with chronic neutrophilic leukemia (CNL), and two with juvenile CML (JCML). Most of the cases with typical CML were Philadelphia chromosome (Ph) positive and had a rearrangement within the major breakpoint cluster region (M-bcr). One of these cases was shown to be Ph positive but showed no rearrangement within the M-bcr. Two cases with clinical features typical of CML were Ph negative. One of these showed a rearrangement within the M-bcr, but no rearrangement was demonstrated in the other. Both patients in blast crisis were Ph positive and M-bcr positive. One showed a second Ph. Patients with aCML were Ph negative and had no M-bcr rearrangement. A polymorphism within the M-bcr was found with BglII in one case. No Ph chromosome or M-bcr rearrangement was found in CNL or JCML. These data support the molecular heterogeneity reported in CML. PMID- 1854885 TI - A study of the myeloid differentiation antigens of the peripheral blood neutrophil granulocytes in the different evolutive phases of chronic myeloid leukemia. AB - To ascertain whether progression from the chronic to the accelerated and blastic phases of chronic myeloid leukemia (CML) is associated with the loss of the myeloid differentiation antigens of the neutrophil granulocytes (NG), we analyzed two monoclonal antibodies (PMN 31D8 and PMN 13F6) recognizing normal peripheral blood NG membrane antigens in 49 patients in different evolutive stages of CML. Since five patients were studied twice, a total of 54 studies were carried out. Fourteen patients were evaluated at diagnosis, 12 in the controlled chronic phase within 1 year from diagnosis, 14 in the advanced chronic phase (median evolution 3.25 years), and 14 in the accelerated (five cases) or blastic (nine cases) phases. Fourteen normal subjects served as a control group. At diagnosis, a significant decrease in the positivity for both antigens was observed with respect to controls, probably due to the circulation of incompletely mature NG. In the early chronic phase the values were within the normal range, whereas a significant decrease was registered in the advanced chronic phase and especially in the accelerated/blastic phase. A negative correlation between the NG positivity for both markers and the time elapsed from the moment of obtaining the initial control of the disease was found, suggesting that a progressive loss of the myeloid antigens of the NG occurs during the evolutive course of CML. These results seem to confirm the usefulness of the NG myeloid differentiation antigen study as an evolutive parameter in CML. PMID- 1854886 TI - Cyclosporin for hypereosinophilic syndrome. AB - The idiopathic hypereosinophilic syndrome (HES) comprises a heterogeneous group of disorders with unknown pathogenesis characterized by persistent peripheral blood and bone marrow eosinophilia and eosinophil infiltrates of multiple organs, leading to severe organ dysfunction. Lymphokine-mediated T-lymphocyte control of human eosinophilic granulopoiesis is though to play a major role in the pathogenesis of HES. Treatment of this disease with cyclosporin-A (CSA) therefore appears to be sensible. We report the case of a patient with a severe HES who failed to respond adequately to glucocorticoid treatment. With additional CSA therapy, disease activity showed a favorable remission and eosinophil counts rapidly decreased to the normal range and remained normal even after reduction of the methylprednisolone dosage to 7.5 mg daily. To date his remission has continued for more than 6 months. In the meantime we have confirmed the beneficial effects of CSA in two other cases of HES. This suggests that CSA treatment is justified, at least in combination with glucocorticoids, in severe cases of HES to prevent the side effects of a long-lasting high-dose glucocorticoid therapy. PMID- 1854887 TI - Post-transfusion purpura as the main manifestation of a trilineal transfusion reaction, responsive to steroids: flow-cytometric investigation of granulocyte and platelet antibodies. AB - We report a typical case of post-transfusion purpura (PTP) due to anti-PlA1 in a 65-year-old woman. Serological studies were carried out using flow cytometry (FCM). The patient also developed red cell alloantibodies that produced a delayed hemolytic transfusion reaction (DHTR) and broad HLA antibodies. Treatment with high-dose intravenous IgG (HDIgG; a first-generation preparation) was ineffective, but a course of steroids resulted in a rapid increase in the the platelet count. PMID- 1854888 TI - Sebastian platelet syndrome. Two new cases in a Spanish family. PMID- 1854889 TI - [The permeability of thymocyte plasma membranes for calcium ions]. AB - The passive calcium transport through the plasmatic membranes of thymocytes of cattle has been investigated. It has been found that this process is a reaction of the first order. The kinetic values of the reaction have been calculated. PMID- 1854890 TI - [Alkoxyl lipids--relics of the organic world: their formation, biotransformation and evolution]. AB - The data on discovery, biosynthesis and distribution of alcoxylipids in different kingdoms of the organic world, their physiologic role and biologic action are given. A conception of possible abiotic synthesis of alcoxylipids on the early stages of the Earth evolution and the ways of their biotransformation is considered. The first biologic membranes are suggested to contain primarily alcoxylipids. During the appearing of photosynthetic mechanism and its improving the alcoxylipids of biomembranes oxidized in plasmalogens and then into diacyl lipids. The possibilities to use alcoxylipids as chemical makers of biomembranes for chemotaxonomy are under discussion. PMID- 1854891 TI - [The long-term storage of spermatozoa and its role in vertebrate fertilization]. AB - A hypothesis according to which the prolonged sperm storage in female sex tracts optimizes the fertilization process, permitting to synchronize an encounter of completely formed fertile spermatozoa and ovule under the most favourable for syngamy conditions is proposed. Spermatozoa in the state of "conservation" are the main source of male gametes under internal fertilization. Synchronization in encounter of gametes is achieved by the action on sperm-storage structures of follicular fluids, which brings about evacuation of a portion of sperm-storage structures to be in time with ovulation: yield, reactivation and advancement of sperm to the site of fertilization. The activating agents of follicular fluids act inside the oviduct. The limited number of spermatozoa is sufficient for successful fertilization. Ovule participates actively in the fertilization process. PMID- 1854892 TI - [The effect of electrostimulation of the locus coeruleus, the medial parabrachial nucleus and the dorsal raphe nucleus on the paired activity of the respiratory center in rats]. AB - Using the electromyographic method in acute experiments on anaesthetized with urethanum rats the different influence of locus coeruleus, nucleus medialis parabrachialis and nuclei raphae on respiratory centre activity has been established. The effect of the locus coeruleus depended on parameters of stimulation and on the character of the tested structures between each other and the bilateral regions of the respiratory centre. PMID- 1854893 TI - [The behavioral and cardiovascular reactions of the young chimpanzee in the 1st month of life]. AB - The analysis of behavioral reactions and cardiac rhythm of 9-30 days old chimpanzees is given. It has been found that the active emotionally negative reaction with signs of avoidance and the passive defensive reaction of fading appear first. This behavioral reactions are reflected in the mechanisms of the cardiovascular system regulation. The active defensive reaction is accompanied by tachycardia growing from the beginning up to realization, and the passive defensive reaction is accompanied by bradycardia. The emotional reactions influence the tonus of floating nerve even at this age. PMID- 1854894 TI - Detection of protein deposition on contact lens type polymeric hydrogels by Coomassie blue R staining. AB - Using an aqueous solvent of high methanol content, we have been able to extend the use of Coomassie blue R protein staining to contact lens-type acrylate hydrogels of 35-80% water content. Protein deposition on a wide range of hydrogels was compared after exposure to protein and there was good agreement between in vitro and in vivo studies to assess deposit resistance. Staining was sensitive down to a 2 micrograms lysozyme/cm2 zone extending from one polymer surface to the other, and linear with protein content up to 40 micrograms/cm2. The staining method permits unusual deposit morphologies to be easily visualized and is best used for qualitative or semiquantitative evaluation of protein deposition during the development of new polymeric materials. We propose a new classification system for protein deposition based on the degree of Coomassie blue R staining. PMID- 1854895 TI - Biocompatible polyphosphazenes by radiation-induced graft copolymerization and heparinization. AB - Investigations were carried out on the radiation-induced graft copolymerization by direct irradiation of dimethylaminoethyl methacrylate on to poly(bis(trifluoroethoxy)phosphazene) and on to poly (bis(phenoxy)phosphazene). Kinetics of grafting were followed with the polyphosphazenes immersed in monomer methanol mixtures of various composition. The grafted film samples were quaternized with methyl iodide and, to the produced ammonium group, heparin was ionically bonded with high yield. On the grafted and heparinized-grafted film samples an evaluation of hydrophilicity, mechanical properties, biocompatibility and anticoagulating properties was carried out. PMID- 1854896 TI - Wound management with N-carboxybutyl chitosan. AB - In patients undergoing plastic surgery, donor sites were treated with soft pads of freeze-dried N-carboxybutyl chitosan to promote ordered tissue regeneration. Compared to control donor sites, better histoarchitectural order, better vascularization and the absence of inflammatory cells were observed at the dermal level, whilst fewer aspects of proliferation of the malpighian layer were reported at the epidermal level. Accordingly, N-carboxybutyl chitosan leads to formation of regularly organized cutaneous tissue and reduces anomalous healing. PMID- 1854897 TI - X-ray photoelectron spectroscopy analysis of the surface chemical structure of some biodegradable poly(orthoesters). AB - The surface analysis of some biodegradable poly(orthoesters) has been undertaken using X-ray photoelectron spectroscopy (XPS). There is very good agreement between the experimental and theoretical surface compositions. All the carbon environments of the poly(orthoesters) are detected within the high-resolution C1s peak envelopes and again, good agreement is observed between the theoretical and experimental proportions of each carbon environment. The data confirm the high surface purity of these polymers and demonstrate the potential for the use of XPS in future studies of the solid state in-situ degradation of poly(orthoesters). PMID- 1854898 TI - In vivo and in vitro degradation of poly(3-hydroxybutyrate) in rat. AB - The inflammatory activity and biodegradation of poly(3-hydroxybutyrate) were examined. Poly(3-hydroxybutyrate) sheet did not cause any inflammation in the chorioallantoic membrane of the developing egg. The i.v. injection of 14C labelled poly(3-hydroxybutyrate) granules showed that 86, 2.5 and 2.4% of the total radioactivity administered were distributed in the liver, spleen and lung, respectively, and the radioactivity decreased slowly but steadily in most tissues examined during 2 month. Crude extracts of rat tissues showed that the activity degraded the poly(3-hydroxybutyrate) granules in vitro. PMID- 1854900 TI - New collagen implant as dural substitute. AB - A collagen prosthesis was developed as a dural substitute. It is composed of a Dallop matrix-polyester knitted net with radiation cross-linked collagen on both sides. Collagen was derived from enzyme-treated bovine Achilles tendons. Improved hydrophilic properties of the polyester base ensuring stronger adhesion to collagen were obtained by pretreating the net with a low-temperature plasma in air. Cross-linking of collagen and simultaneous sterilization of the final prosthesis was obtained by irradiation with 5 MeV electrons. Measurement of the physicochemical parameters of the prostheses gives satisfactory results. In vitro biological examinations show that the prostheses are non-toxic. The results of in vivo clinical experimental evaluation are positive and lead to the conclusion that the collagen-covered polyester net does not differ significantly from Zenoderm dural substitute. PMID- 1854899 TI - In vitro association of type III collagen with elastin and with its solubilized peptides. AB - Elastin fibres or elastin solubilized peptides associated with type III collagen, under physiological conditions, to form a gel-like substance. The gel cohesion could be markedly improved either by desiccation process (gently air-dried rather than lyophilized) or by addition of adhesive connective proteins such as fibronectin, laminin and type IV collagen. They conferred to the material the composition and the structural appearance of typical basement membrane-like structure. Their properties enable us to investigate the biomaterial in several domains. PMID- 1854901 TI - Effect of surface hydrophilicity on ex vivo blood compatibility of segmented polyurethanes. AB - The relationship between surface, bulk and ex vivo blood-contacting properties of segmented polyurethanes with various polyol soft segment was investigated. The polyols used in this study were poly(ethylene oxide), poly(tetramethylene oxide), hydrogenated poly(butadiene), poly(butadiene) and poly(dimethylsiloxane). The hard segment of these segmented polyurethanes was composed of 4,4' diphenylmethane diisocyanate and 1,4 butanediol, present at 50 wt%. An experimental polyurethane, Biostable PUR, which has shown excellent biostability, was used in this study. The segmented polyurethanes based on the hydrophobic polyols such as poly(dimethylsiloxane) and hydrogenated poly(butadiene) showed distinct microphase separation between hard and soft segments. X-ray photoelectron spectroscopy revealed the surface enrichment of the hydrophobic component at the air-solid interface. Dynamic contact angle measurements indicated that the poly(dimethylsiloxane)-based segmented polyurethane possessed a hydrophobic surface in water. The poly(dimethylsiloxane)-based segmented polyurethane had the lowest platelet adhesion among the segmented polyurethanes investigated in this study, whilst the platelet deposition on the poly(ethylene oxide)-based polymer increased with time. PMID- 1854902 TI - Soft filamentous woven polyester arterial prosthesis from China. AB - Woven polyester arterial prostheses have traditionally been known for their tight construction and smooth surface which has limited their healing capacity and resulted in poor attachment of their internal and external capsules. A new woven prototype has recently been developed in the Peoples' Republic of China. Among its unique features are its high physical porosity, softness and flexibility. This study undertook a series of in vitro tests to characterize its structure and physical properties in comparison with four commercial polyester grafts of North American origin. In addition, an animal trial was completed in which the new prototype was implanted as an infrarenal aortic substitute in 20 dogs for periods ranging from 4 h to 12 month. The in vitro tests confirmed a unique lightweight, highly porous, satin weave construction. Because of its high water permeability, preclotting was necessary before implantation. Once preclotted and installed, no significant blood loss was observed, and 19 of the 20 grafts remained patent at the sacrifice. Rapid full-width healing was achieved with tightly bound capsules, and more extensive tissue ingrowth was observed. Further work is needed to evaluate its long-term durability as an arterial substitute. PMID- 1854903 TI - Long-term behaviour of active glasses in sheep mandibular bone. AB - Granules of a glass (A) prepared according to Hench's formula and a new vitreous material for biological applications (AKRA 15) were used for repair of bone defects in the dental field. The behaviour of these materials implanted in holes drilled in sheep's mandibular bone was examined 4, 8, 12 month after implantation. Microradiographic analyses, optical and scanning electron microscopic observations, and X-ray microprobe evaluations were carried out using undecalcified, methacrylate-embedded sections of the jaw containing the granules. After one year the granules of A disappeared, but not important bone growth was observed also in the holes containing AKRA 15. SEM and microprobe showed: disappearance of Na and Si ions at different stages; increase of P and Ca up to 4 month and then decrease, but in different ways in the two glasses; unexpected appearance of K ions after 4 month only in AKRA 15. PMID- 1854904 TI - [Structural description of the human eye using Petri nets]. AB - Petri nets are a tool for analysing and modelling processes and systems. Here they are used to describe the human visual canal for the first time. A dynamic net describes the formation of a glaucoma. PMID- 1854905 TI - [Measuring electric impedance of organs--methodologic principles]. AB - Ischemia causes changes in organ tissue (e.g. during operation or transplantation) which may finally lead to irreversible injury, so that the organ can no longer be resuscitated. To the extent that these changes affect the electrical properties of the tissue they are manifested in the impedance spectrum. As an example, the course of impedance of a HTK-protected porcine liver is presented in the frequency range of 0.1 Hz to 10 MHz, which includes two dispersion--alpha- and beta-dispersion. Using a suitable electrical equivalent circuit analogue to the structure of the liver, the behavior of the alpha- and beta-dispersion is explained on the basis of gap junction closure and narrowing of the extracellular space due to cell swelling. PMID- 1854906 TI - A device for functional residual capacity controlled biofeedback of respiratory resistance. AB - A computer-aided procedure is presented providing subjects with analogous visual feedback of respiratory resistance, which is continuously measured using the forced oscillation method. Simultaneous pneumotachographical control of the breathing volume curve makes it possible to prevent reinforcement for decreases of respiratory resistance which are due to increases of functional residual capacity (FRC). Lung hyperinflation is an unsuitable way to reduce respiratory resistance; if it occurs, feedback is interrupted until the subject decreases his FRC to its initial level. Analysis of the data of 15 adult asthmatic subjects which underwent a 12-sessions feedback training showed that no substantial changes of FRC appeared within feedback trials. Advantages of this new biofeedback technique compared to other procedures are discussed with regard to volume control and feedback signal. PMID- 1854907 TI - Passive viscoelastic properties of the rabbit aorta in vitro. AB - Tensile tests on longitudinal and circumferential strips of the rabbit aorta have been performed. Stress-strain and relaxation parameters have been estimated with respect to four stress levels and three positions on the aorta. Stress-strain data indicate that in longitudinal direction the aorta becomes more compliant with distance from the aortic arch. The opposite tendency is found for the circumferential direction. Stress-relaxation is found to be strongly dependent on the stress level. The results are discussed with regard to arterial dynamics. PMID- 1854908 TI - Cladistic methods and chromophyte phylogeny. AB - An examination of systematic methods is undertaken to establish interrelationships within the chromophytic algae, focussing on their relationship to the Oomycota. Evidence from both molecular and morphological studies suggests that the Oomycota appeared before the pigmented chromophytes. Theories on the origin of the chromophyte chloroplast are examined in the light of these findings. PMID- 1854909 TI - A proposed phylogeny of the flagellated protostelids. AB - The flagellated members of the group of mycetozoans known as protostelids have been recognized for some time to be members of a monophyletic group which also includes the myxomycetes. This inference was based primarily upon comparisons of the flagellar apparatus of the amoeboflagellate state. However, more detailed comparisons based on the whole life history and comparisons with an outgroup were necessary to have information sufficient to determine the interrelationships within the group. Recent studies of the other states of the life history of protostelids have provided a wealth of additional morphological and developmental characters such that an in depth phylogenetic analysis is possible. The results show that the group can be resolved into two major clades, one of which contains the myxomycetes and the myxomycete-like protostelid genera, Protosporangium, Clastostelium, and Ceratiomyxa, and another which contains the protostelid genera Planoprotostelium, Cavostelium, and Ceratiomyxella. As the myxomycetes appear to be part of the ingroup, and not a sister group to the protostelids, L.S. Olive's subclass Protostelia must be considered paraphyletic. PMID- 1854910 TI - Fossils as keys to evolution in fungi. AB - Both flagellated and nonflagellated fungi have an extensive fossil record, which is, however, unevenly documented and often difficult to interpret. Recent work on Silurian, Devonian and Carboniferous terrestrial assemblages has provided plausible evidence for all major groups of extant fungi in the Paleozoic. Key events in fungal macroevolution thus probably took place in the early Paleozoic or the late Precambrian, and the likelihood of finding definitive fossil evidence for them is small. The fossil record also provides evidence for morphological conservatism and early establishment of a spectrum of intimate associations between fungi and vascular plants. A model for the origin of terrestrial fungi involving two distinct lines of biotrophs in lichen-like symbioses with algae is proposed. PMID- 1854911 TI - A model for diurnal patterns of carbon fixation in a Precambrian microbial mat based on a modern analog. AB - Microbial mat communities are one of the first and most prevalent biological communities known from the Precambrian fossil record. These fossil mat communities are found as laminated sedimentary rock structures called stromatolites. Using a modern microbial mat as an analog for Precambrian stromatolites, a study of carbon fixation during a diurnal cycle under ambient conditions was undertaken. The rate of carbon fixation depends primarily on the availability of light (consistent with photosynthetic carbon fixation) and inorganic carbon, and not nitrogen or phosphorus. Atmospheric PCO2 is thought to have decreased from 10 bars at 4 Ga (10(9) years before present) to approximately 10(-4) bars today, implying a change in the availability of inorganic carbon for carbon fixation. Experimental manipulation of levels of inorganic carbon to levels that may have been available to Precambrian mat communities resulted in increased levels of carbon fixation during daylight hours. Combining these data with models of daylength during the Precambrian, models are derived for diurnal patterns of photosynthetic carbon fixation in a Precambrian microbial mat community. The models suggest that, even in the face of shorter daylengths during the Precambrian, total daily carbon fixation has been declining over geological time, with most of the decrease having occurred during the Precambrian. PMID- 1854912 TI - Archamoebae: the ancestral eukaryotes? AB - The archezoan phylum Archamoebae Cavalier-Smith, 1983 is here modified by adding a new order Phreatamoebida (presently containing only Phreatamoeba) and removing the family Entamoebidae. Entamoebidae are instead tentatively placed as a class Entamoebea together with the classes Heterolobosea, Percolomonadea and Pseudociliatea in the new protozoan phylum Percolozoa Cavalier-Smith, 1991. Thus emended the phylum Archamoebae is more homogeneous; it is more distinguished from the other two phyla of the primitively amitochondrial kingdom and superkingdom Archezoa (i.e. Metamonada and Microsporidia) by having kinetids with only a single flagellum and basal body and a flagellar root consisting of a cone of evenly spaced microtubules. This unikont character of the archamoebae suggests that they may be ancestral to the tetrakont Metamonada, from which the non flagellate Microsporidia possibly evolved. Higher eukaryotes (superkingdom Metakaryota) probably evolved from a tetrakont metamonad by the symbiotic origin of mitochondria and peroxisomes. If so, the Archamoebae are the most primitive extant phylum of eukaryotes; if molecular phylogenetic studies confirm this idea, Archamoebae will deserve intensive study, which could reveal much about the origin of the eukaryote condition and also establish what is truly universal among eukaryotes. Archamoebae, like other Archezoa, lack mitochondria and peroxisomes and have no obvious Golgi dictyosomes. Their evolutionary significance is discussed and a detailed classification is presented in which the two earlier classes are merged into a single one: Pelobiontea Page, 1976 stat. nov., containing two orders Mastigamoebida Frenzel, 1892 (Syn. Rhizo-Flagellata Kent, 1880 non Rhizomastigida auct.) (including Mastigamoeba, Mastigina, Mastigella, Pelomyxa and probably a few other genera, which have one or more flagella or cilia (motile or immotile, 9 + 2 or otherwise) in the amoeboid trophic phase), and Phreatamoebida ord. nov. (including only Phreatamoeba in the new family Phreatamoebidae, which has alternating phases of non-flagellate amoebae and uniflagellate cells). Mastigamoebida are divided into three families: Mastigamoebidae Goldschmidt, 1907; Mastigellidae fam. nov.; Pelomyxidae Schulze, 1877. Archamoebae may be uni- or multi-nucleate and either gut parasites or (more usually) free-living in soil, freshwater, or marine habitats. Some can form cysts that would probably fossilize; the earliest (1450 My old) smooth-walled fossil cells large enough to be probable eukaryotes might therefore be archamoebal cysts. PMID- 1854913 TI - Paleozoic Foraminifera. AB - The approximately 300 million years that make up Paleozoic time saw the evolution of eight of the fifteen recognized suborders of Foraminifera. Of the suborders present in the Paleozoic, seven are morphologically relatively simple, slowly evolving, and continued into Mesozoic and Cenozoic times to become the ancestoral lineages from which evolved several additional post-Paleozoic suborders. In contrast, an eighth Paleozoic suborder, the Fusulinina, was an abundant, ecologically dominant group that evolved from simple to highly specialized forms and had a history of rapid evolution with diverse lineages. Fusulinines became extinct at the end of the Paleozoic. Their early representatives may have given rise to three and eventually four post-Paleozoic suborders. A number of suborders in the Paleozoic have similar, supposedly independent, early evolutionary patterns with the following series of morphological steps: (1) single chambers with or without apertures depending on the amount of wall cement; (2) groups of chambers that appear to be buds or aggregations of individuals rather than true chambers; (3) a proloculus followed by a tubular second chamber that is first erect and gradually evolves into enrolled free-living individuals; (4) development of constrictions in the tubular chamber; and finally (5) evolution of true chambers. These morphological steps, which are basic organizational steps with evolutionary significance, appear in lineages with quite different test compositions and, therefore, are considered only distantly related in the present classification. PMID- 1854914 TI - Microtubular spindle and centrosome structures during the cell cycle in a dinoflagellate Crypthecodinium cohnii B.: an immunocytochemical study. AB - In order to determine if a mitotic spindle organizing center is present in dinoflagellate cells, we used a library of 12 monoclonal antibodies obtained by immunizing mice with isolated human centrosomes. When tested by immunofluorescence on cryosections of the dinoflaggelate Crypthecodinium cohnii B., a positive labeling was obtained with three of these antibodies. In interphase cells, the anti-centrosome antibodies labeled structures located either in the cell periphery, corresponding probably to both basal bodies (i.e. kinetosomes) and in the perinuclear area. In the latter case, two punctate structures were observed near the nuclear envelope. They have never been described, either in light, or in electron microscopic studies of dinoflagellates. We have designated them as centrosome-like structures. A microtubular desmose reacting positively with anti-tubulin Ab was also visible, linking kinetosomes and centrosome-like structures. During mitosis, the double punctate structures were observed at the poles of the nucleus. Double immunolabeling with tubulin and anti-centrosome Ab was also carried out and strongly suggested that in mitotic cells, centrosome-like structures, located at the poles of the mitotic spindle, were associated with microtubular bundles and probably organize and polarize them. These data indicate the existence of centrosome-like structures in C. cohnii cells and the strong conservation of some centrosomal epitopes from dinoflagellates to human. One of the antibodies (CTR 210) recognized by immunoblotting, a single protein band at 72 kDa from a total protein extract. The direct demonstration that this protein is located at the centrosome-like structures and at the kinetosomes deserves further study. PMID- 1854915 TI - Phylogeny of the colonial green flagellates: a study of 18S and 26S rRNA sequence data. AB - A study of phylogenetic relationships of the colonial green algal flagellates based on nuclear 18S and 26S rRNA sequence data suggests that the colonial habit has had at least two independent origins. All colonial taxa included in the analysis, except Stephanosphaera, are allied in a clade with Chlamydomonas reinhardtii and other Chlamydomonas taxa ascribed to the Euchlamydomonas group by Ettl. In contrast, Stephanosphaera is allied with other unicellular flagellates including Haematococcus. Comparison of the 18S and 26S data shows that the two sets of data yield different results following cladistic analysis. The 18S data provide the principal signal that supports the more basal divergences, but the data do not unambiguously address relationships among taxa in the clade that includes most colonial flagellates and Chlamydomonas taxa representative of the Euchlamydomonas group (sensu Ettl). In contrast, the 26S data have fewer informative sites that support basal divergences than the 18S data, but provide much of the signal that supports resolution of taxa in the colonial flagellate clade in an analysis of the combined 18S and 26S rRNA sequence data. Additional sequence data from the 26S molecule and additional taxa may reduce the topological ambiguity inferred from the sequence data for the colonial flagellates. Alternatively, an ancient and rapid radiation of taxa in the colonial lineage could account for the topological ambiguity. Despite some unresolved questions of relationships, cladistic analysis of the combined data sets provides some robustly supported concepts of evolution in these flagellates. PMID- 1854916 TI - [Episodic progression of periodontitis--histologic associations]. AB - Periodontal lesions are primarily diagnosed using the periodontal probe. Using site-specific probing attachment level measurements in defined time intervals, dentists can identify patients and dentition segments that suffer temporarily from a high periodontitis progression rate. The present article describes whether sites where clinical measurements suggested a high progression rate had tissue characteristics different from nonprogressing sites. Ten patients with untreated advanced adult periodontitis were monitored for 10 months by measuring clinical parameters every 30 days. These parameters were gingival index, plaque index, bleeding index, bleeding on probing, probing depth and probing attachment levels. Every month pairs of contralateral sites were sought where one site had lost 2 mm (P-2) or more (P greater than 2) probing attachment (P-sites) and the other site had not (C-site). From these sites supracrestal soft tissue biopsies were taken. After histological processing, a first analysis determined the number of inflammatory cells in 9 standard areas in P- and C-biopsies. A second analysis evaluated cell populations at the apical end of the junctional epithelium. The results showed that bleeding on probing, probing depth and probing attachment loss were statistically significantly greater at P-sites. At C-sites there were only few inflammatory cells. At P-2-sites there were numerous inflammatory cells, and in P greater than 2-sites the number of these cells was statistically significantly greater than in corresponding control sites. The cell populations at the apical end of the junctional epithelium were different between P- and C sites. At P-sites, the percentage of mast cells, monocytes/macrophages and plasma cells was statistically significantly greater than at C-sites. At C-sites, the percentage of fibroblasts was statistically significantly greater than at P sites. These results demonstrate that clinical probing identifies episodes of periodontitis progression, which are associated with pronounced changes in tissue characteristics, namely greater numbers of inflammatory cells. PMID- 1854917 TI - [Intensive studies seminar for dental prophylaxis]. AB - The significant role oral prophylactic measures play in the prevention of caries and periodontal disease and the importance of continuing systematic treatment for patients suffering from periodontitis have been scientifically documented in clinical studies. Practical application of this knowledge on a day-to-day basis in dental offices has thus far been hampered by the shortage of appropriately trained personnel. In September 1989, the Zahnarztekammer Berlin founded the "Intensive Studies Seminar for Dental Prophylaxis". In a one-year, vocational course of study, participants acquire the knowledge and practical skills necessary to establish and maintain a system of prophylactic treatment capable of being integrated into the dental practice. The purpose of the following article is to give information concerning the concept behind the program, as well as to introduce the course of study and its various aspects. The experiences gained in the program's first year were positive, and graduates of the course are in demand. It is therefore to be hoped that the concept underlying this seminar will take hold. PMID- 1854918 TI - [Collagen as a basic element of the periodontium: immunohistochemical aspects in the human and animals. 2. Cementum and periodontal ligament]. AB - Immunohistochemical knowledge of the distribution of the collagen types in the cementum and periodontal ligament were reported in this paper. Because of the different localization of each of these collagenous components in the two periodontal tissues its function in the matrix was explored. It was also possible to clarify the role of collagen in healthy periodontium as well as in regeneration and wound healing mechanisms. PMID- 1854919 TI - [Rehabilitation of partially edentulous cases with telescope crowns: modified, fully veneered tapered crowns]. AB - Telescope crowns are well established as prosthodontic retainers for removable partial dentures. After a short review of the advantages and disadvantages of telescope crowns, the specifies of tapered crowns are described. By the use of appropriate tooth preparation and the fabrication of modified, fully resin veneered tapered crowns, it is possible to improve on the crown contours and the aesthetics provided by conventional tapered crowns. Periodontal prophylactic conditions are also considered. PMID- 1854921 TI - [Glossary of basic definitions for dental practice]. PMID- 1854920 TI - [The Pontic. Preventive consideration of pontic design]. AB - When fixed partial dentures are provided for edentulous areas of the alveolar ridge, the previously impaired masticatory and phonetic functions as well as esthetics are restored immediately; in the long run, the restoration helps to stabilize the occlusion, thus maintaining the integrity of the temporomandibular joints and the neuromuscular system. The reabsorption of connective tissues following the loss of teeth as well as the changes in the dimensions of edentulous areas that occur over time will have to be taken into account in that the basic shape of the tooth or teeth to be replaced needs to be modified. Pontics usually present a larger surface than natural teeth; on this surface, plaque may accumulate. The self-cleaning mechanisms are ineffective on the surfaces facing the adjacent teeth or the tissues of the alveolar ridge. For this reason, the pontics and their flexible or rigid connectors to the abutments must be considered the weakest parts of the restoration. The long-term success of the restoration, once periodontal treatment and optimum prosthodontic care have been provided, depends on whether considerations of periodontal prevention played a role in the design of the restoration and on postinsertion periodontal care. PMID- 1854922 TI - [Interdental brushes and toothpicks--presentation of useful prophylaxis articles]. PMID- 1854923 TI - [65 years ARPA/DGP--development of periodontology in the Federal Republic of Germany]. AB - A review of the founding and development of the German ARPA (Association for Periodontal Research) and the ARPA International is presented. Those researchers who shaped and influenced the ARPA were also instrumental in the development of periodontics in Germany. The changes in nomenclature and therapeutic concepts over the decades are also depicted. In 1970 the ARPA became the DGP (German Society of Periodontology). The DGP was one of the founders of the Journal of Clinical Periodontology. In Germany over the past few decades, an attempt has been made to place periodontics in its appropriate position within dentistry with respect to teaching and research. PMID- 1854924 TI - [Teamwork in the dental practice with special regard to periodontology]. AB - A prophylactically oriented concept of periodontal treatment is inconceivable without purpose-trained personnel. This fact led to the new profession of dental hygienist, being introduced into many countries more than 15 years ago. In Germany, attempts were made to close the gap with the profession of dental assistant (ZMF). This model has, however, proved a failure because--besides the advanced training curriculum not being sufficiently specialized--the demand for dental assistants is far greater than the supply. Many dentists, therefore, employ assistants with relevant training in the form of updating courses. Apart from the fact that this frequently results in legal misgivings, it also fails to meet the demand. For this reason, it is absolutely essential that personnel structures be adapted nationwide to a prophylactically oriented concept of periodontal treatment. Account is being taken of experience already gained abroad, as well as current opportunities for training and advanced training in Germany, including the legal principles valid in this country. PMID- 1854925 TI - [Methods aimed at lengthening the clinical crown: a review]. AB - This review deals with the different methods of lengthening the clinical crown and discusses the advantages and/or disadvantages of each method. Different flap procedures, including ostectomy and osteoplasty, reduce the height of the alveolar crest aiming at a distance of about 3 mm to a future reconstruction margin. Root planing may avoid reattachment of surgically separated fibers. Other methods like gingivectomy, electrosurgery, intra-alveolar transplantation, and forced eruption might contain considerable biological disadvantages. However, if the extrusion is combined with regular fiberotomy, this method becomes the most conservative with respect to the periodontal tissues of neighboring teeth. On the other hand, not all situations which require lengthening of the clinical crown can be solved by orthodontic extrusion and fiberotomy. Therefore, depending on the clinical problem, either the surgical lengthening of the clinical crown or the orthodontic extrusion with separation of the fibers are the recommended procedures. PMID- 1854926 TI - [Subgingival irrigation in periodontal therapy]. AB - Subgingival plaque control is a decisive factor in periodontal therapy. Up to the present, removal of plaque and calculus by repeated scaling procedures has been regarded as the only viable method to achieve this goal. Recent investigations, however, suggest that the topical application of antibacterial substances or subgingival irrigation procedures are capable of yielding comparable improvements of periodontal health. This review paper is dedicated to subgingival irrigation. Besides an overview of techniques and results, we discuss our own experiences, including two case presentations. The results so far are encouraging. Nevertheless, due to the general lack of scientific data with extended time intervals, this method is not suitable yet as an alternative to conventional procedures in periodontal routine care. Until further long-term evidence has been gathered, subgingival irrigation should be regarded only as a valuable adjunct to scaling and root planing. PMID- 1854927 TI - [Treatment of a patient with advanced periodontitis]. AB - This case report presents the planning and clinical treatment of a patient with advanced periodontitis and insufficient prosthetic reconstruction. After initial therapy with extraction of the unrestorable teeth, periodontal surgery was performed partly by means of the implantation of hydroxyapatite into bony defects. The prosthodontic treatment consisted of a fixed/removable prosthesis in the maxilla, together with a shortened teeth arch in the mandible. This clinical treatment, combined with regular recalls, has ensured the patient a functional and esthetic reconstruction for a period of 4 years. PMID- 1854928 TI - [Glossary of basic definitions for dental practice. Use of clinical indexes in daily dental practice]. PMID- 1854929 TI - [Interplak--a new concept for mechanical plaque removal]. PMID- 1854930 TI - [Interventional radiology. A cooperative future for radiologists and surgeons]. PMID- 1854931 TI - [Observations on the formation of the secondary venous system of the abdominal cavity with special reference to idiopathic left-sided varicocele]. AB - Based on 1,778 radiologic investigations of vena cava inferior, left renal vein and left spermatic vein the anomalies due to incorrect transformations from the first to the second abdominal venous system are presented. A persistent vena cardinalis posterior could be demonstrated in two cases. Varicoceles were seen with and without insufficient valves of the spermatic vein and venous outflow obstruction of the renal vein, respectively. Based on the demonstrated phlebographies disorders of ontogenesis seem to be the cause of the idiopathic left-sided varicoceles. PMID- 1854932 TI - [CT-guided course-punch biopsy of the adrenals. The indications, technic and results]. AB - Adrenal lesions exceeding 1.5 cm diameter were biopsied with a Tru-Cut needle (G 14) under CT guidance for histologic evaluation in 61 patients. Using CT for guidance, special techniques for safe access to the adrenals are described. Large bore biopsy yielded a sensitivity of 100% and a specificity of 97.4%. Diagnostic accuracy was 98.3%. No significant complications occurred. In comparison to the results of FNA reported in the literature, large-bore biopsy of adrenal lesions improves the rate of adequate material and the histopathologic differentiation without increase of complications. PMID- 1854933 TI - [The skeletal changes in premature infants with a copper deficiency]. AB - We describe 5 preterm infants (25th to 30th week of gestation) suffering from alimentary copper deficiency. The diagnosis was confirmed by low serum copper and caeruloplasmin concentrations. Characteristic clinical findings were repeated apnoeic attacks, hypopigmentation of skin and hair, anaemia, neutropenia and leucopenia refractory to other therapy, as well as increasing serum alkaline phosphatase activity in the first month of life. Starting in the 3rd to 12th week of life the radiographic findings were general skeletal osteoporosis and retardation, metaphyseal radiodense lines, irregular metaphyses, cupping and spurring of the metaphyses, followed by multiple fractures and subperiosteal new bone formation and enlarged costochondral junctions. Copper was substituted orally resulting in complete healing of fractures and improvement in both clinical symptoms and laboratory parameters. PMID- 1854934 TI - Denta Scan: CT software program used in the anatomic evaluation of the mandible and maxilla in the perspective of endosseous implant surgery. AB - A radiological technique, using a new CT software program for the evaluation of alveolar process height and width, is presented. Irradiation is kept within acceptable limits when this technique is used. Measurements obtained with this technique were compared with those obtained on panoramic radiographs in 40 "half jaws" (21 maxillar and 19 mandibular). We found that new indications for implantation emerge in the mandibular region because 'Denta Scan' can sometimes show possibilities to place implants on the buccal side of the canal (2 of 19 mandibular cases) when no possibilities are present above the canal on both the panoramic radiographs and Denta Scan images. In the maxillar region Denta Scan avoids unnecessary interventions by demonstrating the insufficient width of the alveolar ridge, often missed on panoramic radiographs (4 of 21 maxillar cases). Moreover the use of Denta Scan allows the use of implants with optimal length and diameter (23 of the 40 cases), giving better long-term results. PMID- 1854935 TI - [Computed tomography of the upper mediastinum. Optimized contrast media application by the use of an infusion pump]. AB - The aim of this study is to show the advantages of a power injector for contrast media application in comparison to manual bolus injection. The evaluation of 144 studies showed significant improvements for the examinations using the power injector based on densitometry in selected vessels (average enhancement 348 vs 280%) as well as subjective evaluation of contrast quality (3.4 pts vs 2.3 pts on a subjective scale) and contrast-induced artifacts (1.8 vs 2.3 on a subjective intensity scale). All parameters show that an increased, more reliable, and homogeneous enhancement can be obtained by application of the power injector compared to manual bolus injection technique using the same amount of contrast media (100 cc). Due to the possible standardisation of this technique, the results are reproducible. Increased reliability in expected diagnostic gain can be obtained using our technique for intravenous contrast application. This introduced technique requires no additional monetary or time expense and is therefore applicable for clinical routine work. PMID- 1854936 TI - [The percutaneous ultrasonic-guided fluoroscopy-controlled drainage of pericardial fluids]. AB - The results of 25 ultrasonographically guided percutaneous pericardial drainage procedures and of one pericardiocentesis performed in 25 patients with pericardial fluid collections are reported. After initial puncture of the pericardial cavity under sonographic guidance, dilatation and placement of 5F to 8.3F catheters in Seldinger technique was controlled fluoroscopically in 22 procedures. Clinical indications were emergency treatment of tamponade (n = 6) or urgent treatment of large (n = 14) pericardial effusions. The remaining 6 procedures were performed to establish specific diagnoses of small effusions. Puncture sites were subxiphoid in 23 and left parasternal in 3 cases. The volume of aspirated fluid ranged from 20 to 1710 ml (median: 615 ml). Median duration of pericardial drainage was 3 days (range less than 1 day to 21 days). A specific diagnosis was obtained in 48% of patients. 4 patients had subsequent elective surgical intervention for recurrent effusion or for pericardial biopsy. Three minor complications included one vasovagal reaction and two asymptomatic pneumothoraces. Percutaneous ultrasonically guided and fluoroscopically controlled placement of a pericardial catheter is safe and effective for treatment and diagnosis of pericardial effusions. PMID- 1854937 TI - [The radiological image of pleural lipomas with special reference to computed tomography]. AB - Diagnostic assessment of focal pleural mass requires CT examination, particularly in follow-up of anamnestic tumour conditions. Since 1976 well-delineated pleural masses that were suspicious for malignancy on chest films, were identified in 11 patients as lipomas, using CT. They showed semicircular, oval or polygonal shape, but no really "spheric" aspect on biplane chest films. Main diameters of these masses were 2.5 to 6 cm and only once 11 cm. Density values mostly ranged from 110 to -70 HE (min. -133, max. -22 HE) in nonenhanced CT studies. Findings were localised adjacent to the parietal pleura seven times (in one patient two separate findings) and to the diaphragmatic pleura five times. In 7751 CT examinations of the chest, the incidence of pleural lipomas was 0.14%, their prevalence concerning solid pleural lesions being 5.3%. Among all intrathoracic lipomas those in mediastinal and paracardial location respectively were definitely more often (30 patients). PMID- 1854938 TI - The value of ultrasound mammography in palpable breast masses. AB - Between January 1987 and May 1988 a prospective study was carried out on 232 women with a palpable breast mass. They underwent physical examination, x-ray mammography and ultrasound mammography. The results of each study were interpreted independently by separate observers, and consensus was achieved. From all solid tumours histology was available. Compared to x-ray mammography, ultrasound mammography proved to be significantly (p less than 0.025) more sensitive in diagnosing malignant palpable breast masses (98.7% versus 86.8%). However there was no statistical significant difference in specificity between ultrasound mammography and x-ray mammography. Using ultrasound mammography we classified 9 histological proven malignant tumours as such which were negative on plain x-ray mammography. Despite the good results of ultrasound mammography in diagnosing palpable breast lesions it can never replace x-ray mammography in cases of malignancy, because the results of ultrasound mammography with non palpable synchronous tumours with or without microcalcifications are poor. In some cases of benign lesions diagnosed with ultrasound mammography no x-ray mammography is necessary. PMID- 1854939 TI - [Intra-arterial chemotherapy in locally advanced breast carcinomas]. AB - Transcatheter arterial chemotherapy with mitoxantrone was carried out in 9 patients suffering from advanced breast cancer. The anticancer agent was selectively injected in the internal mammary artery. In 2 cases the catheter was super-selectively advanced into a peripheral branch of the internal mammary artery supplying the breast carcinoma. No complication of the transcatheter treatment could be observed. CT examinations for controlling the catheter position showed perfusion of breast cancers between 40 and 90 per cent. Histological examinations of the 7 resected specimens revealed extensive necrosis in all cases. All 7 patients who underwent surgery have been without local recurrence for 3 to 12 months after treatment. PMID- 1854940 TI - [Transcranial Doppler sonography in cerebrovascular diseases]. AB - A review of our 1 1/2 years' experience with transcranial Doppler sonography (TCD) is given. In total, 619 TCD examinations were performed. Considering physiological variations of blood flow velocities in the intracranial arteries, TCD findings in stenoses and occlusions of the extracranial and intracranial brain-supplying arteries as well as in intracranial vasospasms were evaluated. In patients with leptomeningeal anastomoses demonstrated by TCD in the region of the peripheral middle cerebral artery, the regional cerebral blood flow was measured by 99mTc-HMPAO-SPECT. The value and limitations of TCD in cerebrovascular diseases and the indications to TCD examination of the intracranial arteries are discussed. PMID- 1854941 TI - [Gliomatosis cerebri: the diagnostic potential of MRT]. AB - Gliomatosis cerebri is a rare tumor of neuroepithelial origin in middle aged persons presented by deterioration of cognitive functions, psychomotor retardation and cerebral convulsions. MRI predominantly shows a bilateral and diffuse infiltration of midline adjacent brain structures including medulla. Areas with focal anaplasia occasionally reveal an accumulation of contrast media. The diffuse tumor manifestation requires a differentiation from encephalitis and demyelinating diseases with a similar distribution pattern of lesions. Three cases have been examined. In conclusion the performance of MRI including control and brain biopsy are indicated to establish an in vivo diagnosis. PMID- 1854942 TI - Progressive hemifacial atrophy: CT findings. A case report. PMID- 1854943 TI - A case of primary osseous pelvic hydatid disease (Echinococcus granulosus). PMID- 1854944 TI - Alternating scoliosis as a symptom of spinal tumour. PMID- 1854945 TI - [The effect of heparin and thromboplastin on the half-life of 125I-protein C in the blood flow of rats]. AB - The influence of heparin and thromboplastin on the halflife of 125I-protein C in rat blood was under investigation. It was found that t1/2 of protein C was of 2.3 h. The intravenous administration of heparin resulted in the prolongation of t1/2 to 6.5 h, that could be explained by inhibition of thrombin generation. Upon the 40-min infusion of thromboplastin the rate of 125I-protein C decay in blood enhanced. That could be explained by the generation of the endogenous thrombin and participation of thrombomodulin in the protein C activation as well as in the removal of the endogenous thrombin from blood. PMID- 1854946 TI - [The effect of calcitonin on the mechanisms of urine formation and sodium excretion in normotensive and spontaneously hypertensive rats]. AB - The effects of the pig calcitonin on the kidney excretory function in normotensive (NR) and spontaneously hypertensive rats (SHR) were examined. Calcitonin injection in the dose of 0.6 U/100 g of the body mass in NR and SHR in the conditions of 6-hour spontaneous diuresis caused the increase in the urination volume due to the inhibition of the tubular water reabsorption and growth of the glomerular filtration rate. The important role in the mechanism of the decrease in the water reabsorption in SHR plays the decrease in the content of vasopressin in the blood and urea in the kidney interstitium while in NR a more marked inhibition of the water reabsorption is caused by the decrease in the concentration of both urea and sodium in the kidney layers. The natriuretic effect of calcitonin was noticed only in NR. PMID- 1854947 TI - [The effect of leukotriene LTC4 on the coronary vascular bed and on myocardial contractile function]. AB - The effects of intracoronary LTC4 administration have been studied in narcotized dogs with an intact chest. LTC4 in doses of 0.5-40 micrograms produced a dose dependent decrease in coronary flow, inhibition of myocardial contractility and disturbance of cardiac rhythm. A decrease in myocardial contractility was shown to take place before the signs of myocardial ischemia had appeared that could not be entirely due to the decrease in coronary blood flow. Ultrastructural changes in the endothelium of the coronary vessels have also been observed under the action of LTC4. PMID- 1854948 TI - [Emotional behavioral disturbances in rats administered subconvulsive doses of korazol]. AB - The injection of subconvulsive doses of pentylenetetrazol (corazol, 10 mg/kg, intraperitoneally) leads to the appearance of a complex of the emotional behavioral disturbances in rats which consists of three main syndromes: anxiety, pathologically enhanced fear and inactivation state. Each of syndromes is characterized, by a particular pattern of electrical activity (EA) recorded from brain structures. The bursts of EA (10-11 oscillations per s) with maximum amplitude and duration in locus coeruleus (LC) correspond to the syndrome of anxiety. The wave EA of a frequency coincident with a frequency of rat respiration corresponds to the syndrome of pathologically enhanced fear. The appearance of spindle-like EA (6 oscillations per s) in striatum (STR) corresponds to the syndrome of inactivation state. The amplitude and duration of generalized spindle-like EA are maximum in STR. The change from anxiety to inactivation state is accompanied by the change of corresponding EA patterns. It can be suggested that the injection of subconvulsive doses of pentylenetetrazol in rats leads to LC and STR hyperactivation because of which LC and STR acquired the properties of a pathological determinant whose appearance induces the formation of pathological systems with corresponding clinical manifestations. The relationship between the systems created by LC and STR hyperactivation is of antagonistic character. PMID- 1854949 TI - [The effect of microinjections of morphine and tramadol into the locus coeruleus on the nociceptive responses of the spinal cord neurons and on shifts in the arterial pressure]. AB - Morphine and tramadol produces selective inhibition of the spinal noxious-evoked activity, but does not change blood pressure reactions. Antinociception was reversed by this structure injection of the naloxone. These data suggest that locus coeruleus realized the pain-relief effect of the opiate drugs. PMID- 1854950 TI - [The functional-morphological state of the myocardium in experimental massive embolism of the pulmonary artery]. AB - A comparative study of hemodynamic and structural-metabolic changes in the myocardium of the right (RV) and left ventricles (LV) in acute massive pulmonary artery embolism was made in 19 mongrel dogs. In the control group the activity of SDH, MDH, GDH, NADH-DH in LV were higher than in RV. The numeral density and relative area of mitochondrial profile surface in LV was higher that in RV. A significant increase in afterload on RV causes intensification of cell respiration, a rise in numeral density and relative area of mitochondrial profile surface. Weakening of LV work leads to contrary structural-metabolic changes. Thus, contrary changes in hemodynamic loads on RV and LV in acute compensative massive pulmonary artery embolism correlated with contrary changes in their cell metabolism. PMID- 1854951 TI - [Systemic and regional hemodynamic reactions to metabolic stress caused by 2 deoxyglucose]. AB - Changes in parameters of systemic and regional hemodynamic, elicited by intraarterial administration of 250 or 500 mg/kg of 2-deoxy-D-glucose (2-DG) were studied in the awake Wistar rats with microsphere technique. Measurements were performed before, 15-and 40-min after 2-DG administration. Significant decrease in the heart rate as well as increase in stroke volume were observed 15 min after 2-DG. It was a tendency to increase in cardiac output. Blood flow in skin and skeletal muscles were decreased whereas in the brain, heart, adrenal glands and small intestine there were significant increases in the blood flow. We conclude that hemodynamic responses to 2-DG reflect the effects of humoral (adrenaline) and central sympathetic factors. PMID- 1854952 TI - [The effect of diabetogenic substances on the zinc and calcium content in the pancreatic islet cells of rabbits]. AB - The injections of diabetogenic drugs to rabbits induced a decrease in zinc and calcium content in B insulocytes dependent on the degree of these cells damage and hyperglycemia. The content of these metals in A insulocytes was not significantly altered due to a light injury of these cells. A high concentration of calcium in islet A cells is suggested to be a protective factor to the action of alteration agents. PMID- 1854953 TI - [The convulsive activity of white rats after immunization with a conjugate of sidnofen and serum albumin]. AB - The influence of white rats immunization by a covalent conjugate of serum albumin with sydnophen on the seizure activity in the single and repeated injections of pentylenetetrazole was investigated. The immunization lowered the seizure activity in single injections of threshold doses, (60 mg/kg) of pentylenetetrazole. The repeated daily injections of the drug in subthreshold doses (30 mg/kg) inhibited the process of "kindling" effects formation. PMID- 1854954 TI - [Rhythmic changes in protein synthesis in mouse pancreatocytes after food stimulation, in alloxan diabetes and in isoproterenol exposure]. AB - Radioautography revealed data on protein synthesis dynamics in pancreacytes of intact mice, subjected to alloxan diabetes and isoproterenol (ISP) injection after synchronized secretion. Rhythmic fluctuation of protein synthesis with maximum uptake of 3H-leucine 40 and 80 min after treatment was observed in intact animals. The above maximums correlated with the increase in the cell size. In alloxan diabetes, injections of ISP and their combination the rhythm of protein synthesis is retained, the total intensity of isotope uptake increases significantly, but at the same time secretion periods, particularly in the latter case decrease. The results obtained revealed the existence of endogenic rhythms in protein synthesis with certain secretion plasticity within pancreacytes. PMID- 1854955 TI - [The activation of the early chemiluminescent response of human neutrophils by joint treatment with tumor necrosis factor (TNF-alpha) and the calcium ionophore A-23187]. AB - The influence of recombinant human tumor necrosis factor-alpha (TNF-alpha) and calcium ionophore A23187 on luminol- and lucigenin-dependent chemiluminescence capacity (CL) of human polymorphonuclear leukocytes (PMN) has been studied. The CL response of TNF-alpha treated PMN is amplified by lucigenin, but not luminol. TNF-alpha and A23287 synergistically induced both the luminol- and lucigenin dependent early CL response. The combination of A23187 and activator of protein kinase C--phorbol (myristoyl-13-acetyl)--also provoked early CL response. While the combination of TNF-alpha and A23187 decreased late CL response compared to A23187 alone. The obtained results suggests that synergistic CL response of PMN induced by TNF-alpha and A23187 is connected with activation of protein kinase by TNF-alpha. PMID- 1854956 TI - [Age-related differences in the effect of osmotic pressure on liver mitochondrial respiration in rats]. AB - The subject under investigation is the influence of osmotic pressure of incubation medium (25-500 mM of sucrose) upon the respiration and the respiration control (RC) of mitochondria of the liver of rats aged 1, 3, 12 and 24 months when oxidizing succinate. In a medium with 0.3 M of sucrose the respiration rate under condition 3 (V3) and RC increased from the age of 1 to 12 months and decreased by 24 months. In a medium with 0.15 M of sucrose the age differences have not been observed. In a uncoupling state the osmotic dependence of the respiration of mitochondria of 1- and 12-month-old rats did not vary. It is assumed that with age there is a change in the rate of structural coupling of the carrier of adenine nucleotides with H(+)-ATP synthetase complex and (or) the viscosity of the matrix. PMID- 1854957 TI - [Phosphatase activity in the lymph during a fever reaction]. AB - Activity of acid and alkaline phosphatases, as well as isoenzymes of alkaline phosphatase in the lymph of the thoracic lymphatic duct, hepatic lymph and the peripheral blood have been studied on rabbits in the dynamics of the fever reaction of different duration. The fever reaction was followed by enzyme activity increase in all the body biologic fluids. However the degree of increase of their activity in the lymph was greater that that in the blood. Our data indicate that in the transport of phosphatases released from the tissues in the common circulation the essential role is played by the lymphatic system, the resorption and transport functions of which significantly characterise the dynamics and the level of their changes in the blood in fever reaction. PMID- 1854958 TI - [Benzonal--a phenobarbital-type of inducer of the mono-oxygenase system]. AB - It has been found that the Soviet anticonvulsant drug Benzonal is an inducer of the liver cytochrome P-450 of the phenobarbital type. The drug causes formation of the cytochrome P-450 form which is immunologically identical to the phenobarbital inducible form of the hemoprotein with identical molecular mass determined with the SDS-gel electrophoresis method in PAAG. The microsomes, obtained from the rats treated with Benzonal display increased rates of metabolism of 7-pentoxiresorufin and 16 beta-hydroxylation of androstenedione which are specific substrates for the cytochrome P-450b. PMID- 1854959 TI - [Changes in the emotionally conditioned behavior of rats under the influence of the hexapeptide fragment GLLDLK of the protein inhibitor of diazepam binding]. AB - It is shown that suboccipital injection of 100 micrograms of the gexapeptide GLLDLK (the fragment of endogenous peptide--the inhibitor of diazepam binding) modified (for 1-3 days) the emotionally conditioned behaviour of the rats (the test of "emotional resonance"). This modification was realized in some reinforcement of different behavioural patterns and had signs of anxiety and depression. In the test "social hierarchy" the injection of GLLDLK didn't change significantly the hierarchy in the whole rat society, but in the recipient behaviour the exploratory activity has been changed, the time of grooming increased and the quantity of social contacts decreased. PMID- 1854961 TI - [The evaluation of the efficacy of antihypoxic agents lowering hemoglobin oxygen affinity in acute cerebral ischemia]. AB - Influence of natrii hydroxybutyrate (100 mg/kg), ascorbate (100 mg/kg), cavinton (5 mg/kg), bemitil (50 mg/kg), ethomersol (50 mg/kg) on Hb-O2 affinity and cortex PO2 after both carotid artery occlusion in rats was investigated. Correlation (r 0.87; P less than 0.05) between lowering of Hb-O2 affinity and antihypoxic effect was demonstrated in the line of these drugs. PMID- 1854960 TI - [The role of the Ca2(+)-blocking effect of alcohol in the genesis of ischemic myocardial damage]. AB - The experiments on Wistar male rats with induced myocardial infarction have studied the role of Ca-blocking effect of acute ethanol administration in ischemic injury of myocardium. It has been established that acute alcohol intoxication led to destabilization of adaptive processes in ischemic myocardium. PMID- 1854962 TI - [The characteristics of the cardioprotective action of fructose-1,6-diphosphate]. AB - The cardioprotective effects of fructose-1,6-diphosphate (FDP) were investigated in infarcted rats and in conscious rabbits with myocardial ischemia. The influence of FDP on metabolic acidosis was studied in isolated hypoxic rat hearts. It was shown that FDP did not change the threshold of the initiation of ischemia in conscious rabbits, but decreased necrotic zone in infarcted rat hearts. After administration of FDP the myocardial contractility was prolonged significantly as compared with control under conditions of severe metabolic acidosis. However, FDP was not effective in hypoxic hearts with compensated metabolic acidosis. It was considered, that FDP influenced only ischemic myocytes with the changes in sarcolemmal permeability. PMID- 1854963 TI - [Changes in the profile of cytotoxic mediator monocytes in patients with cancer and precancerous conditions of the stomach]. AB - Peripheral blood monocytes from healthy subjects, patients with gastric precancer disease (chronic gastric ulcer, stomach polyps and chronic atrophic gastritis) and different stages of gastric cancer were used. Spontaneous and lipopolysaccharide (LPS)-stimulated TNF-like factors production by monocytes was significantly higher in the precancer gastric disease patients than in the healthy subjects. At the same time the spontaneous capacity of monocytes to produce NTF-like factors was 2.5 lower in the gastric cancer patients compared to the healthy subjects. Moreover, in 5/13 of the gastric cancer patients in TNF like factors production by the LPS-stimulated and non-stimulated monocytes was 1 unit/ml less. Spontaneous and reactive CL indexes were higher in the cancer patients monocytes than in the healthy subjects. The obtained results suggest that reactive oxygen species production can be an alternative mechanism by which a cytotoxic action of monocytes is regulated. PMID- 1854964 TI - [The resistance of in vivo selected tumor cells of malignant phenotype to the cytolytic action of activated peritoneal macrophages in vitro]. AB - Using radioisotope cytolytic 3H-thymidine release assay the sensitivity of low malignant spontaneously in vitro transformed hamster embryo cells (STHE strain) and its in vivo selected malignant variants (STHE-LM-4, STHE-LM-8, STHE-75/18) as well as Rous sarcoma virus (RSV) (Schmidt-Ruppin strain) tumorigenic transformants (HET-SR-1, TU-SR) were tested to cytolysis by peritoneal Syrian hamster macrophages (MP) activated in vitro with levan, LPS, MDP and PMA. It has been shown that the only parental cells STHE strain (non-selected in vivo) were sensitive to cytolysis by activated MP. All in vivo selected malignant variants of STHE cell sublines as well as tumorigenic RSV-SR-transformants were resistant to cytolysis by activated MP. Thioglycollate-elicited but not activated MP did not destroy any tumour target cells. PMID- 1854966 TI - [The coadaptation of the lymphocyte and neutrophil enzyme systems in intact mice and against a background of infectious exposures]. AB - In experiments on mice the authors studied the correlation of the levels of the activity of a number of enzymes (dehydrogenase and acid phosphatase) of lymphocytes and neutrophils at three levels of organization: subcellular--inside the lymphocytes and neutrophils; intercellular--coordination of the enzymatic activity of two types of blood cells; temporary--inter-conjunction of the levels of metabolism in the blood cells prior to and in dynamics after infection. R. P. Nartsissov's cytochemical method with the use of n-nitrotetrazolium was employed. Introduction of systemic conceptions into the cytochemical analysis of neutrophils and lymphocytes made it possible to reveal a peculiarity of the metabolic status of the blood cells involved into the inflammatory process and also to determine coadaptation elements of the two types of leukocytes. PMID- 1854965 TI - [The significance of chorionic gonadotropin in regulating the antigen-independent differentiation of immunocompetent splenic cells]. AB - The functional activity of fractionated splenocytes were investigated in the syngeneic transfer system. Chorionic gonadotrophin (CG) was injected to ovariectomized and noncastrated lymphocyte donors, the T or B lymphocytes being isolated on a column with a nylon fiber and by means of anti-BaO-serum accordingly. In some series CG was introduced only into recipients before their being irradiated and before syngeneic cells transferring. CG has been stated to be capable of influencing either independently or by means of ovarian hormones splenic B lymphocytes without exhibiting a significant effect on T helper precursors as well as radioresistant cells of the splenic stroma. The character of immunoregulating effect was completely dependent on the presence of ovaries in mice and on the hormone dose. PMID- 1854967 TI - [The characteristics of the programming action of androgens on the formation of sexual dimorphism in the level of corticosteroid-binding globulin in rats]. AB - The role of sex steroids in the programming of the level of serum corticosteroid binding globulin (CBG) of male and female rats has been studied at different stages of ontogenesis. It was shown that castration of adult males lead to the increase of the level of CBG, but not to the elimination of sex differences. Gonadectomy of males up to 28th day of postnatal life results in complete feminization of the CBG content in these animals at the age of 10-12 weeks. The castration after 35th day of life does not prevent the formation of the male phenotype of CBG content. The results of administration of testosterone propionate (TP) to castrated males at different periods of ontogenesis suggests that the sensitivity to irreversible negative action of androgens appears after 28th day of life and disappears after the puberty. It was concluded that short period of ontogenesis from 29th to 35th days of life is critical for the realization of the irreversible masculinization of CBG level upon the influence of androgens in the physiological conditions. It was found that injections of both synthetic estrogens diethylstilbestrol or TP in the sensitive period of ontogenesis lead to the expression of male phenotype of CBG level in a similar fashion. PMID- 1854968 TI - [Vitamin E decreases the neurocytotoxic action of kainic acid in a cerebellar neuron culture]. AB - Using primary cultures of cerebellar granule cells from 4-6-day old Wistar rats we showed the protective effect of vitamin E against kainate-induced neurotoxicity. The preincubation of 7-8-day old cultures with 5 x 10(-4) M alpha tocopherol solution significantly (on 10-20%) reduces the number of damaged granule cells. As vitamin E takes part in stabilization of membrane lipids the data presented allows us to suggest that one of the possible mechanisms of neuronal injury includes lipid oxidation of the neuronal membranes which leads to additional influx of Ca2+ and results in neuronal death. PMID- 1854969 TI - [The function of the liver mitochondria in rats with experimental cirrhosis undergoing an organ-preserving operation on the spleen]. AB - The effect of splenectomy and of spleen-preserving operation with suture ligation of the left gastric artery on the functional status of liver mitochondria was studied by using 102 white male-rats of mixed population with experimental cirrhosis. The obtained data made it evident that in the immediate postoperative period (from 1 to 3 weeks after the procedure) in the animals of both the first and the second series, the disorder of energetic regulation of mitochondria hepatocytes respiration and the decrease in phosphorylation efficiency had the same tendency, which were seemingly caused by stress-action of the operative trauma. The data accumulated in the more distant postoperative period (8 weeks after the procedure) indicated that the resection of the lower splenic pole in combination with supplementary liver arterialization improved essentially the functional status of mitochondria hepatocytes and was more beneficial in contradistinction to splenectomy. PMID- 1854970 TI - [The characteristics of osteogenesis under conditions of stretch tension]. AB - Structure of rough-fibrillar, netted and laminated bone tissues, formed in distraction regenerates on various stages of leg lengthening, was studied experimentally on dogs, using light, transmission and scanning electron microscopy and electron probe microassay. It was ascertained, that the first two types of tissues belong to the category of provisory, rapidly renewing ones, the volume increase of which is possible not only at the expense of appositional growth but also interstitially. Their formation in the area of the regenerate, more proximally and more distally than the medial layer, provided longitudinal growth of primary osteons forming here and thereby the growth of the whole bone regenerate. PMID- 1854971 TI - [A comparative radioautographic analysis of DNA synthesis by enterocytes of the small intestine in in vivo and in vitro experiments]. AB - A method of radioautography was used to study DNA synthesis in mice enterocytes as an index of their proliferative activity. Cells were labelled by means of incorporation [3H]thymidine in vivo and in vitro. The program was worked out to computed analysis of the reflected light intensity of obtained radioautographs and estimation of reliability data. Our experiments showed that thymidine diffused very slowly. PMID- 1854972 TI - [The morphometric and immunohistochemical characteristics of the gastric and duodenal mucosa in systemic lupus erythematosus]. AB - Histological, morphometric, and immunohistochemical studies of biopsy specimens from the mucosa of the body and antral portion of the stomach, the bulb and descending portion of the duodenum were performed in 27 children with systemic lupus erythematosis (SLE) and in 12 with chronic gastroduodenitis. The inflammatory infiltrate from SLE patients was found to contain higher levels of young and mature fibroblasts than that from patients with chronic gastroduodenitis, mature fibroblasts being prevalent. The inflammatory changes in the gastric and duodenal mucosa were ascertained to be associated with the progression of SLE. In exacerbation of SLE, the walls of vessels (arterioles) exhibited immune complexes classified mainly as IgG and, to a lesser degree, as IgM. In remission, the luminescence of the vessels decreased. The serum level of immunoglobins did not correlate with their regional production in the gastric and duodenal mucosa. PMID- 1854973 TI - [The cellular polymorphism of the myointimal thickening in the rabbit aorta]. AB - Partly endothelialized myointimal thickening formed in rabbit aorta after balloon catheter injury. It was populated by cells of different shape. There were spindle shaped cells. Y-shaped cells, cells of irregular shape with processes and stellate-shaped cells. As a rule stellate cells situated just near the endothelium. It is supposed, that the endothelium can influence the shape of myointimal cells. PMID- 1854974 TI - [An ultrastructural stereological analysis of the myocardium in homoiothermal animals during cooling]. AB - By methods of electron microscopy and stereology the ultrastructural cardiomyocyte reorganization of rats exposed to influence of low temperatures (exposure during 16 days at -7 degrees C) was studied. It was shown, that with this regime of cooling the disturbance of intracellular regeneration in cardiomyocytes occurred and the complex of morphological changes typical for the syndrome of regenerative-plastic deficiency was developed. The most essential changes were seen in myofibrils and mitochondria. According to the stereologic data a change in spatial reorganization of cardiomyocytes was connected largely with these organelles. With the increase in cooling duration an increase in the volume density of myofibrils and a decrease in this parameter for mitochondria were marked. As a result of these changes the mitochondria/myofibrils volume ratio was essentially decreased. As a whole, ultrastructural reorganization of cardiomyocytes under the influence of low temperatures on rats was characterized by a decrease in the ratio of the organelle volume to myofibrillar volume. The same quantitative reorganization was revealed in atrophied cardiomyocytes under the conditions of the decreased inflow of plastic substances to cells. PMID- 1854975 TI - [Nd:YAG laser radiation alters the proteolytic resistance of the liver tissue proteins in rats]. AB - Small tissue strips were excised from rat liver and exposed to extensive irradiation with Nd:YAG laser followed by homogenization and spectrophotometric detection of 5% TCA-soluble protein fractions (oligopeptides) in both supernatants and 5NKOH-soluble sediments of the irradiated specimens. Trypsin along, or with chemotrypsin was added to the specimens to evaluate their proteolytic resistance during and after incubation for 24 h in the proteinase(s). The results showed that Nd:YAG laser irradiation resulted in significantly more oligopeptides following either schedule of the proteolysis employed in both supernatants and sediments as compared to the unaffected proteolytically tested specimens. At the same time a proteolytically resistant 5% TCA-insoluble fraction was elicited which belonged to proteins and, judging by the parallel ultrastructural data, was located in the cellular membranes. The probable mechanisms of the observed protein modifications, along with some pertinent clinical implications of Nd:YAG laser surgery, are considered. PMID- 1854976 TI - Cell kinetics and hormonal features in relation to pathological stage in breast cancer. AB - Proliferative activity (expressed as 3H-thymidine labeling index, 3H-TdR LI) was evaluated on a series of 281 primary tumors recruited in two years in 6 different institutions from central Italy. 3H-TdR LI proved to be low in intraductal, or well and moderately differentiated, or hormone receptor positive tumors. Conversely, no relation was observed between 3H-TdR LI and menopause, tumor size, or lymph node involvement. An inverse relation was observed between 3H-TdR LI and hormone receptor content. Specific patterns of 3H-TdR LI value and ER content association were observed as a function of menopause, lymph nodal status, and degree of lymph nodal involvement. PMID- 1854977 TI - Steroid hormone receptor activity of primary human breast cancer and pattern of first metastasis. The Breast Cancer Study Group. AB - A series of 258 breast cancer patients with known estrogen receptor (ER) status of the primary tumour who subsequently developed metastases were reviewed for site of first metastasis. In 188 cases progesterone receptor (PgR) data were also available. Univariate analysis showed metastatic patterns to differ statistically significantly related to ER status and (less pronounced) PgR status of the primary tumour. Patients with ER-positive tumours had bone metastases three times more often than patients with ER-negative tumours. With respect to PgR-positive and PgR-negative tumours this frequency differed by a factor of two. With regard to visceral metastases ER and PgR status were equally potent prognosticators, patients with receptor negative tumours having a 50% higher frequency of visceral metastasis than patients with receptor positive tumours. Assessment of metastatic patterns in relation to combined receptor status did not substantially enhance the discriminatory value of ER and PgR when assessed separately. Multivariate analysis showed that the observed differences in metastatic patterns were all attributable to differences in the ER status of the primary tumour, and were not influenced by age, menopausal status, axillary lymph node involvement, duration of disease-free interval (DFI), mode of postoperative treatment, or the PgR status of the primary tumour. PMID- 1854978 TI - Metabolism of debrisoquine and susceptibility to breast cancer. AB - There may exist an association between the genetically determined oxidation status of the antihypertensive agent debrisoquine (DEB) and the propensity to develop tumours. The metabolism of DEB is extensive in 90% of healthy subjects (metabolic ratio = MR = 0-12.6; MR = % DEB excreted divided by % 4-hydroxy-DEB excreted) and poor in 10% (MR greater than 12.6). In patients with cancer of the lung, urinary bladder, and gastrointestinum, the percentage of high metabolizers is increased to greater than 98%. The poor metabolizer mode is almost devoid of cancer patients. It was investigated whether breast cancer patients show a similar association with respect to the oxidative status of DEB. 108 breast cancer patients and 123 women with benign gynecologic disorders received 1 tablet of 10 mg DEB orally in the evening. Urine was collected for the subsequent 8 hrs and analysed for its content of DEB and its main urinary metabolite 4-OH-DEB by means of HPLC. No decreased amount of poor metabolizers was seen in the cancer group. PMID- 1854980 TI - Differential retention of rhodamine 123 by breast carcinoma and normal human mammary tissue. AB - We have qualitatively evaluated the retention of the fluorescent dye rhodamine 123 by malignant or non-malignant breast epithelial cells in passively-infused fresh surgical specimens. Our findings demonstrate a microscopically-visible increase in the ability of primary and metastatic tumor cells to retain the dye, as compared to non-malignant epithelium. Some variability in fluorescence intensity was seen within and between tumor specimens. The optimal length of incubation in the presence of the dye was critical in achieving differential fluorescence intensity between normal and malignant cells. This method of examining rhodamine 123 uptake and retention in tissue explants provides a reliable means for direct, comparative visualization in situ of any tissue and its associated disorders. The results of this study also demonstrate the validity of extending the use of lipophilic, cationic compounds such as rhodamine 123 as antitumor agents, from model systems to the treatment of malignant disease. PMID- 1854981 TI - Video endoscopy, the electronic endoscopy unit and integrated imaging. PMID- 1854979 TI - Randomized study of mammography screening--preliminary report on mortality in the Stockholm trial. AB - In March 1981, 40,318 women in Stockholm, aged 40-64, entered a randomized trial of breast cancer screening by single-view mammography alone versus no intervention in a control group of 20,000 women. The attendance rate during the first screening round was 81 per cent and the cancer detection rate was 4.0 per 1000 women. The detection the rate fell to 3.1 per 1000 in the second round, which was completed in October 1985. During 1986 the controlled design of the study was broken and the control women were invited once to screening which was completed the same year. A total of 428 cases of breast cancer were thus diagnosed in the study group and 439 in the adjusted control group. After a mean follow-up of 7.4 years the number of breast cancer deaths in the study and control groups was 39 and 30 respectively. The relative risk of breast cancer death (screening versus control) was 0.71 (95 per cent confidence interval: 0.4 1.2). Among women older than 50 years at entry the relative risk was 0.57 (95 percent confidence interval: 0.3-1.1). Cancer deaths among women under 50 were few and perhaps because of this no mortality reduction was seen in this age group. The estimate of mortality reduction lies between the results from two earlier Swedish randomized controlled trials. PMID- 1854982 TI - Endoscopy update. PMID- 1854983 TI - Variceal injection sclerotherapy. AB - With the development and widespread use of flexible endoscopes, injection sclerotherapy of oesophageal varices has advanced beyond the early stages. Although slightly different techniques and different sclerosants are used, the results are not strikingly different. The cumulative rate of adverse effects is in the range of 20 to 40%, with a procedure-related mortality of around 1 to 2%. Sclerotherapy is the best available treatment for haemostasis of acute oesophageal variceal bleeding. However, as a long-term therapy it is less effective in the prevention of recurrent gastrointestinal bleeding events, since obliteration of all varices often takes several months. Furthermore, extra oesophageal bleeding is not amenable to sclerotherapy. Thus, if repeated injections fail to prevent recurrent bleeding, other options such as shunt surgery, transection, chronic medical portal decompression with beta-blockers or even liver transplantation should be considered according to the needs of the individual patient. Prophylaxis of first variceal haemorrhage was beneficial in selected patients with a high bleeding risk. It cannot, however, be generally recommended at present. PMID- 1854984 TI - Endoscopic management of pancreatic disease. AB - Since its introduction in 1968, ERCP has developed from being a purely diagnostic method, mostly used in the investigation of unexplained upper abdominal pain, to an invaluable tool for the management of patients with pancreatic disorders. In cases with severe gallstone pancreatitis, the biliary obstruction is disclosed and relieved by ERCP and ES. In patients with severe acute pancreatitis of other aetiologies, as well as in post-traumatic pancreatitis, ERCP is indispensable for revealing complications (e.g. pancreatic duct rupture) and/or for planning the treatment strategy. Furthermore, in cases of pancreatitis not related to alcohol or gallstones, it often demonstrates causes which may be treatable, and it is also useful for evaluation of the gland after massive pancreatic necrosis. Moreover, ERCP is helpful in establishing the diagnosis of chronic pancreatitis and its complications as well as in demonstrating morphological grounds for therapeutic intervention. Although the indications, limitations, and practicability of the different techniques of therapeutic ERCP in various pancreatic diseases still remain to be defined, the method appears to offer an alternative to surgery, particularly in cases in which operative treatment is technically difficult and the results are less favourable. Frequency and severity of complications associated with both diagnostic and therapeutic ERCP seem to be, at least in the hands of experts, reasonably low. PMID- 1854985 TI - The appreciation of colour in endoscopy. AB - The perception of colour at endoscopy has been taken for granted since the discovery of the fibreoptic bundle and the advent of fibreoptic endoscopy. Fibreoptic and lens assemblies can distort the impression of colour by selectively absorbing some wavelengths of light. In the case of electronic endoscopes, the principal sensor is the charge-coupled device (CCD), a small microelectronic device that converts an image into a sequence of electronic signals which, after appropriate processing, are transformed into an image on the monitor screen. The image is therefore visualized as a mosaic of small images, one from each sensing element. Colour is synthesized by using sequential illumination using filters or by filters placed over the CCD. Fibre-endoscopes may alter colour by selectively transmitting certain portions of the visible spectrum, while electronic endoscopes are susceptible to errors due to poor calibration of the instrument and manipulation of the colour controls by endoscopists. Colour information provides the endoscopist with clues to the nature of the lesion and also a site for biopsy. In experimental situations, colour information has been used to determine blood flow and classify lesions. Much work needs to be done to define normal and abnormal colour in the gastrointestinal tract and to develop a standard terminology for colour nomenclature in endoscopy. PMID- 1854986 TI - Endoscopic ultrasonography of the upper gastrointestinal tract. AB - EUS unites two established imaging techniques and extends the range of observation into and beyond the wall of the GI tract. The close proximity of the sonographic probe to the region of interest combined with high ultrasonic frequencies of between 7.5 and 12 MHz yields images of high resolution. EUS is used in the staging of benign and malignant neoplastic disorders of the oesophagus, stomach, pancreas and extrahepatic bile ducts. It helps to establish operability, to plan surgical approach, to follow response to therapy and to search for recurrence. The predictive value in defining the T and N stages of oesophageal carcinoma lies between 80 and 90% and 65 and 85%, respectively. It is clearly superior to CT in tumour stages T1 and T2. In gastric cancer, resectability based on the TNM staging system can be correctly assessed by EUS in 85% of cases and EUS detection and staging of early gastric cancer reaches an accuracy of 90%. The EUS accuracy rate for resectability of pancreatic carcinoma is 83% and tumour infiltration into the portal and splenic vein can be correctly determined by EUS in 94% and 67%, respectively. A reliable EUS differentiation between chronic pancreatitis and pancreatic carcinoma based on the echo pattern and outer margins is not possible. The development of EUS-guided needle biopsy should improve the specificity of EUS in this regard. Experience to data suggests as well that EUS will assume an important place in the staging of bile duct tumours. EUS has expanded our endoscopic and sonographic capabilities and it is to be hoped that further technical improvement, e.g. the construction of forward viewing endoscopes combined with radial scanning devices, will contribute to a widespread use of this technique by gastroenterologists. PMID- 1854987 TI - Balloon technology and its applications in gastrointestinal endoscopy. PMID- 1854988 TI - Primary colonoscopy. AB - There is good evidence that colonoscopy, in expert hands, is the most accurate investigation for the diagnosis of colorectal disease, and it also allows histological confirmation and therapeutic procedures to be carried out. Furthermore, by screening high-risk groups together with regular follow-up of patients with known colorectal neoplasia and surveillance of long-standing ulcerative colitis patients, it may be possible to reduce the incidence of colorectal cancer. However, at the present time, the lack of widespread availability and the variability in the quality of examinations precludes the employment of colonoscopy as the first-line investigation in colorectal disease. Flexible sigmoidoscopy combined with good quality double contrast barium enema is a reasonable alternative in the majority of cases, reserving colonoscopy for investigation of the elderly and high-risk patients, together with surveillance of patients with premalignant conditions. Technologically, colonoscopy has probably reached its peak and it is now necessary to make provision for more widely available colonoscopy services, provided by adequately trained endoscopists who can guarantee total colonoscopy in more than 90% of cases safely and rapidly. This requires structured training programmes for gastrointestinal physicians and surgeons and ultimately changes in patterns of working practice if adequate numbers of colonoscopy sessions capable of dealing with a steadily increasing workload are to be achieved. PMID- 1854989 TI - Monitoring and safety in endoscopy. AB - Over 50% of the complications and 60% of the deaths associated with upper GI endoscopy are cardiopulmonary in type. Oxygen desaturation and cardiac arrhythmias at the time of endoscopy are common. Ways of trying to prevent hypoxia occurring are discussed. The most effective of these is the use of supplemental oxygen. Pulse oximeters are being used increasingly frequently by endoscopists. The way in which oximeters work is described in some depth, as are some of the potential errors that may result from their use. The author believes that, as in anaesthetic practice, pulse oximeters will be used ever more frequently by endoscopists and finally become standard equipment in all endoscopy units. The case for using continuous ECG monitoring and blood pressure measurement is briefly discussed. The ASGE have recently published their recommendations on monitoring patients undergoing GI endoscopic procedures. The BSG's own working party on safety and monitoring is in the process of finalizing its recommendations, and the final part of the chapter discusses the views of this working party and gives some insight into what its final recommendations are likely to be. PMID- 1854990 TI - The place of endoscopy in the management of gallstones. PMID- 1854991 TI - Disappearance of oxyfluorfen (goal) from onions and organic soils. PMID- 1854992 TI - Persistence of the insecticide dimethoate in three different soils under laboratory conditions. PMID- 1854993 TI - Fate of the fungicide tolylfluanid in the pear cold stored in controlled or non controlled atmosphere. PMID- 1854994 TI - Extraction of pesticides from soil leachate using sorbent disks. PMID- 1854995 TI - Dissipation of alachlor under in situ and simulated vadose zone conditions. PMID- 1854996 TI - Organochlorine pesticides in cow's milk from agricultural region in northwestern Spain. PMID- 1854997 TI - Transport of a BTX mixture in a groundwater aquifer material. PMID- 1854998 TI - Determination of crop-specific parameters used in foliar mass to area conversion: I. For selected varieties of grapes. PMID- 1854999 TI - Microtox assay of trinitrotoluene, diaminonitrotoluene, and dinitromethylaniline mixtures. PMID- 1855000 TI - Blood aluminum levels as a function of aluminum intake from drinking water. PMID- 1855002 TI - Effects of salinity on the toxicity of parathion to the estuarine crab Chasmagnathus granulata (Decapoda, Grapsidae). PMID- 1855001 TI - Mutagenicity assays of leachate from domestic waste landfills in Japan: the establishment of a protocol for measuring mutagenicity levels of leachate. PMID- 1855003 TI - Acute toxicity of parathion and 2,4 D to estuarine adult crabs. PMID- 1855004 TI - In vivo effects of cadmium chloride on certain aspects of protein metabolism in tissues of a freshwater field crab Barytelphusa guerini. PMID- 1855005 TI - Volatilization of mercury compounds and utilization of various aromatic compounds by a broad-spectrum mercury resistant Bacillus pasteurii strain. PMID- 1855006 TI - Interactions between trichlorfon and three Chlorophyceae. PMID- 1855007 TI - Effects of water-borne copper and lead on the peripheral blood in the rosy barb, Barbus (Puntius) conchonius Hamilton. PMID- 1855008 TI - Influence of Pb, Cd, Zn, Mn, Cu, Hg, or Be salts on the glutathione S transferases of the rat liver. PMID- 1855009 TI - Synergism and antagonism induced by three carrier solvents with t-retinoic acid and 6-aminonicotinamide using FETAX. PMID- 1855010 TI - Drugs, HIV, and prisons. PMID- 1855011 TI - Consultants, contracts, and fundholders. PMID- 1855012 TI - Baby stealing. PMID- 1855013 TI - Randomisation. PMID- 1855014 TI - Juniors' new deal on hours. PMID- 1855015 TI - Persistence of antibody after accelerated immunisation with diphtheria/tetanus/pertussis vaccine. AB - OBJECTIVE: To determine the persistence of antibody to diphtheria, tetanus, and pertussis in children receiving an accelerated schedule of primary immunisation. DESIGN: Controlled study of antibody testing of blood samples from children immunised according to various schedules: three doses of triple vaccine completed at 8-13 calendar months, 6-7 calendar months, before 6 calendar months, or three doses followed by diphtheria/tetanus before age 2. SETTING: Plymouth Health Authority. SUBJECTS: 129 children aged 4 years who had received three doses of diphtheria/tetanus/pertussis vaccine with or without a diphtheria/tetanus booster. MAIN OUTCOME MEASURES: Diphtheria and tetanus antitoxin concentrations and antibody titres to pertussis toxin, filamentous haemagglutinin, and agglutinogens 2 and 3. RESULTS: All children had protective concentrations of antitoxin to diphtheria and tetanus (greater than or equal to 0.01 IU/ml). There was no evidence of a significant difference in diphtheria or tetanus antitoxin concentrations and pertussis antibody titres in children immunised with an accelerated course (third dose of triple vaccine before 6 months) compared with those who received a longer course (third dose at 8-13 months) with no booster (geometric mean antitoxin concentration 0.411 (95% confidence interval 0.273 to 0.618) v 0.426 (0.294 to 0.616) for diphtheria and 0.358 (0.231 to 0.556) v 0.299 (0.197 to 0.453) for tetanus; geometric mean antibody titres 903 (500 to 1631) v 1386 (848 to 2266) for pertussis filamentous haemagglutinin, 179 (130 to 248) v 232 (167 to 322) for pertussis toxin, and 2002 (1276 to 3142) v 3591 (2220 to 5809) for agglutinogens 2 and 3). CONCLUSION: Immunisation with three doses of triple vaccine at monthly intervals completed before 6 months of age probably provides adequate protection against diphtheria, tetanus, and whooping cough which will persist until the age of the preschool booster. PMID- 1855016 TI - Relation between nicotine intake and Alzheimer's disease. AB - OBJECTIVE: To study the association between Alzheimer's disease and nicotine intake through smoking. DESIGN: Population based case-control study. SETTING: City of Rotterdam and four northern provinces of The Netherlands. SUBJECTS: 198 patients with early onset Alzheimer's disease, 198 controls matched for age and sex, and families of 17 patients in whom Alzheimer's disease was apparently inherited as an autosomal dominant disorder. MAIN OUTCOME MEASURES: Age of onset of dementia, relative risk of Alzheimer's disease. RESULTS: 89 of 193 patients with Alzheimer's disease had a history of smoking compared with 102 of 195 controls. Among the patients and controls with a family history of dementia, smoking was significantly less common in those with dementia (40/95 with dementia v 55/96 controls; relative risk 0.35; 95% confidence interval 0.16 to 0.78). The risk of Alzheimer's disease decreased with increasing daily number of cigarettes smoked before onset of disease (relative risk 0.3 in those smoking greater than 21/day v 1 in non-smokers). In six families in which the disease was apparently inherited as an autosomal dominant disorder, the mean age of onset was 4.17 years later in smoking patients than in non-smoking patients from the same family (p = 0.03). CONCLUSIONS: These findings suggest an inverse association between smoking and Alzheimer's disease, although smoking cannot be advocated for other health reasons. We speculate that nicotine may have a role in the aetiology of both Alzheimer's disease and Parkinson's disease. PMID- 1855017 TI - Can computer aided teaching packages improve clinical care in patients with acute abdominal pain? AB - OBJECTIVE: To compare three methods of support for inexperienced staff in their diagnosis and management of patients with acute abdominal pain--namely, with (a) structured data collection forms, (b) real time computer aided decision support, and (c) computer based teaching packages. DESIGN: Prospective assessment of effects of methods of support on groups of doctors in one urban hospital and one rural hospital. SETTING: Accident and emergency department at Whipps Cross Hospital, London, and surgical wards of Airedale General Hospital, West Yorkshire. PATIENTS: Consecutive prospective series of all patients presenting to each hospital in specified time periods with acute abdominal pain; total patients in the various periods were 12,506. MAIN OUTCOME MEASURES: Diagnostic accuracy of participating doctors, admission rates of patients with non-specific abdominal pain, perforation rates in patients with appendicitis, negative laparotomy rates. RESULTS: Use of any one modality resulted in improved diagnostic accuracy and decision making performance. Use of structured forms plus computer feedback resulted in better performance than use of forms alone. Use of structured forms plus a computer teaching package gave results at least as good as those with direct feedback by computer. CONCLUSIONS: The results confirm earlier studies in suggesting that the use of computer aided decision support improves diagnostic and decision making performance when dealing with patients suffering from acute abdominal pain. That use of the computer for teaching gave results at least as good as with its use for direct feedback may be highly relevant for those who are apprehensive about the real time use of diagnostic computers in a clinical setting. PMID- 1855019 TI - Golf related head injuries in children. PMID- 1855018 TI - Intra-articular distension and steroids in the management of capsulitis of the shoulder. AB - OBJECTIVE: To determine whether there is any synergistic effect in the administration of intraarticular steroids with distension in the management of early capsulitis of the shoulder. DESIGN: Prospective randomised trial of three treatments--namely distension only, steroid only, and steroid with distension. SETTING: Academic department of orthopaedic and accident surgery at Queen's Medical Centre, Nottingham. SUBJECTS: 47 patients (30 women) with capsulitis affecting 50 shoulders. INTERVENTIONS: Three intra-articular injections into the shoulder given at six week intervals by the same technique. MAIN OUTCOME MEASURES: Passive range of abduction, forward flexion, and external rotation; results of shoulder dynamometry measuring work done and torque produced; pain levels at rest and with resisted movement. RESULTS: All patients reported improvement during the study. Analysis of the mean improvements in abduction and forward flexion showed these to be significantly greater in the steroid with distension and steroid only groups than in the distension only group (mean improvements in abduction (degrees/week (95% confidence interval)) 4.3 (3.4 to 5.2), 3.4 (2.4 to 4.5), and 1.0 (-0.8 to 2.8) in the three groups respectively; mean improvements in flexion (degrees/week (95% confidence interval)) 3.6 (3.2 to 4.0), 3.3 (2.3 to 4.3), and 1.5 (0.5 to 2.5) respectively). Shoulder dynamometry failed to show a significant difference among the treatment groups. No severe complications occurred as a result of the injections, but two patients reported facial flushing related to the use of steroids. CONCLUSION: Intra-articular steroid injections have a useful role in the outpatient management of early capsulitis. PMID- 1855020 TI - Intravenous drug misuse among prison inmates: implications for spread of HIV. PMID- 1855021 TI - Drug misuse and sharing of needles in Scottish prisons. PMID- 1855022 TI - Sexual behaviour in Scottish prisons. PMID- 1855024 TI - The future of general practice: Personal care or the polyclinic? PMID- 1855023 TI - Twenty five years of case finding and audit in a socially deprived community. AB - OBJECTIVE: To evaluate audit and case finding (whole population care) in a community over 25 years. DESIGN: Contemporary screening for and audits of care of chronic disease and risk factors; retrospective review of computerised practice records; and comparisons of mortality and social indices with neighbouring communities. SETTING: One general practice in Glyncorrwg, West Glamorgan. SUBJECTS: 1800 people registered with the practice in 1987 and 558 people who died from 1964 to 1987, whose records had been retained. MAIN OUTCOME MEASURES: Detection of high blood pressure, smoking, airways obstruction, obesity, diabetes, and alcohol problems in adults aged 20-79; prevalence of smoking in this population and in hypertensive and diabetic groups; age standardised mortality ratios in relation to indices of social deprivation. RESULTS: In the population aged 20-79 (1207 patients) 249 (21%) had peak expiratory flow rate less than 50% of expected value or which improved by 15% or more with an inhaled beta agonist, 207 (17%) had body mass index at or over 30 kg/m2, 118 (10%) had untreated mean arterial pressures greater than 159/104 mm Hg (three readings), 80 (7%) (65 (16%) men, 15 (4%) women) had recognised alcohol problems, and 35 (3%) had diabetes. The proportion of men aged 20-64 who said they smoked fell from 61% (290/476) in 1968-70 to 36% (162/456) in 1985 whereas that of women who smoked was unchanged (43%, 187/436 v 42%, 190/448 respectively). In 116 screened hypertensive patients group mean blood pressure fell from 186/110 mm Hg before treatment to 146/84 mm Hg at 1987 audit, as did the proportion of smokers (56% v 20%), but body mass index and total cholesterol concentration showed no significant change. In 34 diabetic patients mean blood pressure and the proportion of smokers fell (171/93 mm Hg v 155/81 mm Hg; 44% v 12%). The age standardised mortality ratio in 1981-6 was lower than in a neighbouring village without a developed case finding programme (actual to expected deaths less than 65 = 21 to 22 in Glyncorrwg, 48 to 30 in control village). CONCLUSIONS: Whole population care through organised case finding and audit is feasible but only with a labour intensive approach combining accessibility, flexibility, and continuity, as well as a planned and structured approach, which requires substantial expansion of staff numbers and assiduous recording. It may reduce risks for at least some high risk groups. Despite their shortcomings the available data are consistent with the hypothesis that whole population care helps reduce mortality. Incentives in the new contract, which encourage the uncritical development of structured process, may diminish health outputs. PMID- 1855025 TI - "Heartstart Scotland"--initial experience of a national scheme for out of hospital defibrillation. AB - OBJECTIVE: To determine the outcome of out of hospital defibrillation in Scotland during the year after the introduction of automated external defibrillators in October 1988. DESIGN: Retrospective analysis of ambulance service reports and hospital records. SETTING: Scottish Ambulance Service and acute receiving hospitals throughout Scotland. MAIN OUTCOME MEASURES: Delay from cardiac arrest to first defibrillator shock; vital state on arrival at hospital accident and emergency department; survival to hospital discharge. RESULTS: During the study period 268 defibrillators were purchased by public subscription and 96% of the 2000 ambulance crew underwent an eight hour training programme in cardiopulmonary resuscitation and defibrillation. A total of 1111 cardiac arrests were recorded, and defibrillation was indicated and undertaken in 602 (54%) patients, mean age 63 (range 14-92) years. A spontaneous pulse was present on arrival at hospital in 180 (30%) of the defibrillated patients, and 75 (12.5%) were subsequently discharged alive. As expected, the likelihood of survival was inversely related to the delay from the onset of cardiac arrest to the time of the first shock and was greater in the case of witnessed arrest. If ventricular fibrillation occurred after the arrival of the ambulance, survival to discharge was 33%. CONCLUSIONS: An effective scheme for out of hospital defibrillation can be introduced rapidly, and with limited training implications and costs, by the use of automated external defibrillators in ambulances. PMID- 1855026 TI - The south Manchester Accident Rescue Team and the earthquake in Iran, June 1990. PMID- 1855028 TI - ABC of antenatal care. Antepartum haemorrhage. PMID- 1855027 TI - Your child is dead. AB - OBJECTIVE: To determine parent's views on how death of their children should have been handled. DESIGN: Retrospective questionnaire survey of parents who had experienced death of their child. SETTING: Charitable organisation of bereaved parents. SUBJECTS: 150 bereaved parents, all members of the organisation, of whom 120 (80%) participated voluntarily in the study. MAIN OUTCOME MEASURES: Child's age; date and cause of death; details of person breaking the news and handling of the interview; time parents spent with dead child, their attitude to requests for organ donation, and follow up support received. RESULTS: 122 children's deaths were described; the largest single group was due to road traffic accidents, 16 were suicides, and eight were murders. Twice as many interviews were rated as sympathetically or reasonably handled as badly or offensively handled (68 v 34). The interview ratings depended on the sensitivity and personal skills of the interviewers rather than on their previous contact or professional position; police were rated as more sympathetic than doctors and nurses. Of 109 respondents, 81 had seen their child's body, 44 of whom thought that sufficient time had been denied. Of the 28 parents who did not see the body, 17 subsequently stated their regret. In 82 parents organ donation had not been discussed. Only 16 parents recorded any follow up support from hospital staff and very few support at the time. CONCLUSIONS: The consistency of the responses suggests a serious need to revise the in service training and education of the police and health professionals in their approach to informing of death; organ donation should be discussed sensitively and parents allowed time with their dead child with fewer restrictions. PMID- 1855029 TI - Junior doctors' hours. PMID- 1855030 TI - Helicobacter pylori infection and gastric cancer. PMID- 1855031 TI - Helicobacter pylori infection and duodenal ulcer. PMID- 1855032 TI - Lithium and non-steroidal anti-inflammatory drugs. PMID- 1855033 TI - Deaths of patients waiting for coronary surgery. PMID- 1855034 TI - The cyclotron saga continues. PMID- 1855035 TI - What determines the age at the menopause? PMID- 1855036 TI - Increasing the uptake of cervical smear testing among Asian women. PMID- 1855037 TI - The new NHS: restricting GPs' access to x ray services. PMID- 1855038 TI - The vaso-occlusive crisis of sickle cell disease. PMID- 1855039 TI - Non-operative management of blunt splenic injury. PMID- 1855040 TI - AIDS spreads eastward. PMID- 1855041 TI - Siriraj stroke score and validation study to distinguish supratentorial intracerebral haemorrhage from infarction. AB - OBJECTIVES: To develop a simple, reliable, and safe diagnostic tool for acute stroke syndromes in a setting where computerised brain scanning was not readily available and to validate its accuracy with regard to pathological types of stroke. DESIGN: 13 clinical variables that potentially might differentiate supratentorial cerebral haemorrhage from infarction were recorded and tested by multivariate analysis in a prospective study of 174 patients with acute stroke. In developing the Siriraj stroke score stepwise discriminant analysis of the variables was followed by a linear discriminant equation to differentiate between supratentorial haemorrhage and infarction. The score obtained was validated against scores in 206 other patients with stroke, computerised brain scans being used for definitive diagnosis. SETTING: Siriraj Hospital Medical School, Mahidol University, Bangkok. SUBJECTS: Prospective study: 174 consecutive patients with acute supratentorial stroke syndrome (not subarachnoid haemorrhage) admitted to Siriraj Hospital during 1984-5; validation study: 206 patients admitted to Siriraj Hospital or another hospital for supratentorial intracerebral haemorrhage or infarction. RESULTS: The Siriraj stroke score was developed and calculated as (2.5 x level of consciousness) + (2 x vomiting) + (2 x headache) + (0.1 x diastolic blood pressure) - (3 x atheroma markers) - 12. A score above 1 indicates supratentorial intracerebral haemorrhage, while a score below -1 indicates infarction. The score between 1 and -1 represents an equivocal result needing a computerised brain scan or probability curve to verify the diagnosis. In the validation study of the Siriraj stroke score the diagnostic sensitivities of the score for cerebral haemorrhage and cerebral infarction were 89.3% and 93.2% respectively, with an overall predictive accuracy of 90.3%. CONCLUSION: The Siriraj stroke score is widely accepted and applied in hospitals throughout Thailand as a simple and reliable bedside method for diagnosing acute stroke. PMID- 1855042 TI - Complications of pregnancy and delivery in relation to psychosis in adult life: data from the British perinatal mortality survey sample. AB - OBJECTIVE: To evaluate whether events occurring at or around the time of birth contribute to the onset of psychotic illness in adult life. DESIGN-Pregnancy and birth complications as possible causes of adult mental illness were studied in the population sample of the British perinatal mortality survey. Subsequent psychiatric admissions were independently identified through the Mental Health Enquiry and records of regional and special health authorities. Logistic regression was used to compare data on perinatal deaths with those on survivors to determine factors independently associated with perinatal death, and this equation was then used to calculate the risk of perinatal death for each survivor. SUBJECTS: 16,980 people born in a single week in 1958 (the British perinatal mortality survey sample), including 252 patients admitted to psychiatric care; case notes of 235 patients were supplied. MAIN OUTCOME MEASURES AND RESULTS: Patients with a schizophrenic illness (whether defined by "broad" (n = 57) or "narrow" (n = 35) diagnostic criteria) did not have a greater mean risk of perinatal death than the population in general, but there was some evidence of increased liability (relative risk 2.43; 95% confidence interval 1.17 to 5.05) for those with affective psychosis (n = 32). Specific high risk variables for affective psychosis were decreased gestation time (273.9 v 281.2 days; mean difference 7.3 days, 95% confidence interval 3.1 to 11.5; p less than 0.002) and prescription of vitamin K to the child in the first week of life (19% of patients v 5% of controls, p = 0.016). CONCLUSIONS: The findings give no support to theories that factors predicting perinatal mortality contribute significantly to causation of schizophrenic illness. Further investigation of decreased gestation length in relation to affective disorder is required. PMID- 1855043 TI - Infant feeding practices and ulcerative colitis in childhood. PMID- 1855044 TI - Somatic component to myocardial infarction: three year follow up. PMID- 1855045 TI - Fundholding in general practice and financial risk. AB - OBJECTIVE: To estimate the financial effect of random yearly variations in need for services on fundholding practices with various list sizes. DESIGN: A simulation model was derived using historical data on general practitioner referrals for the 113 surgical procedures covered by the general practitioner fund, combined with data on the hospital prices for those procedures. PATIENTS: Resident population of Central Birmingham Health Authority. MAIN OUTCOME MEASURES: Expected expenditure on the relevant surgical procedures for the whole district and for practices with list sizes of 9000, 12,000, 15,000, 18,000, 21,000, or 24,000 for each of 100 simulated years. RESULTS: By using average hospital prices for the West Midlands region the mean (SD) annual expenditure for the 179,400 residents was 4,832,471 pounds (87,149 pounds); the random variation between the 5th and 95th most expensive years was 5.7% of the mean cost. For a practice with a list size of 9000 the values were 244,891 pounds (18,349 pounds), with a variation of 27.5%. With a list size of 24,000 the values were 652,762 pounds (32,512 pounds), with a variation of 15.3%. CONCLUSIONS: Random variations in need for inpatient services will have a significant financial impact on the practice fund. The problem will be particularly great for smaller practices. Additional measures are required to ensure that the scheme is not undermined and that the potential benefits are secured. PMID- 1855046 TI - Out of hours work in general practice. PMID- 1855047 TI - Need for relevance in management information systems: what the NHS can learn from industry. PMID- 1855048 TI - Women and scuba diving. PMID- 1855049 TI - ABC of antenatal care. Small for gestational age. PMID- 1855050 TI - Eye injuries in racquet sports. PMID- 1855051 TI - Home nebulisers. PMID- 1855052 TI - A methodological quibble about QALYs. PMID- 1855053 TI - Prevalence of asthma in Melbourne schoolchildren. PMID- 1855054 TI - Randomised controlled trials of surgical procedures. PMID- 1855055 TI - Preventing needlestick injuries. PMID- 1855056 TI - The cyclotron saga continues. PMID- 1855057 TI - Tuberculosis and HIV infection. PMID- 1855058 TI - Use of thalidomide in leprosy. PMID- 1855059 TI - HIV infection and hepatitis B in adopted Romanian children. PMID- 1855060 TI - Morphine for painful crises in sickle cell disease. PMID- 1855061 TI - Birth weight, current body weight, and blood pressure. PMID- 1855062 TI - Hospital case notes and medical audit. PMID- 1855063 TI - Screening in general practice. PMID- 1855064 TI - Efficiency of referral for suspected glaucoma. PMID- 1855065 TI - Swallowed coins. PMID- 1855066 TI - A victim of AIDS--or medical negligence? PMID- 1855067 TI - Proceedings of the international course on Bone Marrow Transplantation in Children. 28 November-1 December, 1990, Erice, Italy. PMID- 1855068 TI - Bone marrow transplantation for immunodeficiencies and osteopetrosis. PMID- 1855069 TI - The role of high dose therapy and autologous bone marrow transplant in children with malignancies. PMID- 1855070 TI - Autologous bone marrow transplantation in pediatric solid tumors: phase II studies. PMID- 1855071 TI - Unpurged autologous bone marrow transplantation for neuroblastoma: the AIEOP-BMT group experience. PMID- 1855072 TI - ENSG 1-randomised study of high-dose melphalan in neuroblastoma. PMID- 1855073 TI - Did BMT change the clinical course of neuroblastoma? PMID- 1855074 TI - Allogeneic bone marrow transplantation in children from other than HLA-identical sibling donor. AB - Optimal allogeneic bone marrow transplantation (BMT) presupposes the use of a HLA identical sibling as donor. Unfortunately, only about 30% of patients have an HLA matched donor, so that the use of alternative donors has been increasingly used. We report an analysis of 13 children transplanted using an HLA-partially matched donor as source of haemopoietic stem cells. They suffered of ALL (3 pts), ANLL (1 pt), SAA (2 pts), Osteopetrosis (1 pt), Wiskott-Aldrich Syndrome (2 pts), Severe Combined Immunodeficiency Disease (2 pts) and Familial Haemophagocitic Lymphohistiocytosis (2 pts). Full engraftment was obtained in all 11 of the patients who survived longer than 14 days and, globally, a moderate incidence of acute GvHD (grade II-IV) was observed in the evaluable patients (3 out of 11 with a percentage of 27%); only a patient of the six survivors more than one hundred days after BMT had severe chronic GvHD (16.6%). Four pts (31%) are actually alive and well (mean follow-up 358 days) with a mean Karnofsky score of 95%. Our data suggest that BMT from HLA-partially matched donors could represent a possible alternative therapeutic strategy in children when a compatible donor is not available. This is especially due to the reduced severity of GvHD in childhood and because of T-cell depleted marrow transplants could obtain more satisfactory results when employed in typical pediatric non-malignant disorders (i.e. immunodeficiencies) rather than in leukemia. PMID- 1855075 TI - Successful allogeneic bone marrow transplantation in a child affected by Fanconi anemia. PMID- 1855076 TI - Autologous bone marrow transplantation in secondary acute monoblastic leukemia following Hodgkin's disease. AB - Acute non lymphocytic leukemia (AnLL) is the most common second malignancy (SM) in survivors of childhood Hodgkin's Disease (HD). Chemotherapy responsiveness is usually poor and death ensues briefly after diagnosis. We report the case of a 13 year-old girl, affected by HD, stage IV, mixed cellularity, who developed AnLL one year after the HD treatment was stopped. Autologous Bone Marrow Transplantation (ABMT) was performed 9 months after complete remission (CR) was achieved by chemotherapy. Presently, the patient is alive and on continues CR, 3 years and 7 months after ABMT. ABMT may be a promising approach for secondary AnLL, the prognosis of which is almost invariably fatal with conventional chemotherapy. PMID- 1855077 TI - MYCN amplification does not affect survival of neuroblastoma patients treated with autologous bone marrow transplantation. AB - From an extended series neuroblastoma cases evaluated for MYCN amplification (MNA) at the "G. Gaslini" Hospital 15 (4 with and 11 without NMA) underwent myeloablative therapy and bone marrow transplantation (MAT-ABMT). Such cases ranged in age at diagnosis from 13 months to 7 years and were followed up at least 8 months after MAT-ABMT. MNA was present in 2/10 cases dead for disease, in 0/1 cases alive with disease, and in 2/4 cases presently in complete clinical remission. This preliminary evidence would discourage to consider MNA as a marker capable of predicting the final outcome of patients with metastatic Nb. PMID- 1855078 TI - Use of the highly polymorphic DNA marker CRI-S232 for monitoring of engraftment and chimerism following bone marrow transplantation. PMID- 1855079 TI - Familial haemophagocytic lymphohistiocytosis treated with allogeneic bone marrow transplantation. PMID- 1855080 TI - Role and perspectives of BMT in ALL: the BFM experience. PMID- 1855082 TI - The use of recombinant human granulocyte macrophage colony-stimulating factor in autologous bone marrow transplantation. AB - Phase I, II trials indicate that Recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF), stimulates recovery of neutrophils following myelosuppressive chemoradiotherapy. In Seattle it was administered to patients undergoing autologous bone marrow transplant (ABMT) for lymphoid malignancy. The data indicate that rhGM-CSF was well tolerated and associated with earlier neutrophil recovery, fewer infections and shorter initial hospital duration. Survival was not improved, however, less regimen-related toxicity was observed. Studies in patients with marrow graft failure are strongly suggestive of improved survival and rhGM-CSF is recommended for therapy in those patients. Although numbers were small, results in pediatric patients were not significantly different than results in adults. PMID- 1855083 TI - Autologous bone marrow transplantation for acute lymphoblastic leukemia: the high dose vincristine study of AIEOP BMT group. AB - This study was performed in 5 pediatric centers. It considered a group of children affected by acute lymphoblastic leukemia (ALL) treated with ABMT. 56 patients were considered, 35 males and 21 females, with a median age of 11 years. The children were transplanted in 2nd (36) or subsequent (20) complete remission. The mean of 1st remission duration was 32 months. Analysis of the sites of relapse before transplantation showed that 39 patients had bone marrow relapses, 17 patients had CNS and/or testicular isolated relapses only. 32 harvests were purged in vitro by 1 mcgr/ml Vincristine and 30 mcgr/ml Prednisone, 16 by 100 mcgr/ml Mafosfamide, 8 were not cleaned. 29 patients received high dose Vincristine (4 mg/m2), TBI (1200 cGy), Cyclophosphamide (3600 mg/m2) as standard conditioning regimen before transplant. 27 patients received other conditioning treatments with (14) or without (13) TBI. Of the 56 children 25 relapsed from 1 to 42 months after ABMT, 7 toxicity related deaths were registered and 1 death for second tumor was observed. 23 children remained in continuous complete remission from 1 to 49 months after transplantation. The probability of EFS at 4 years was 21%. High dose Vincristine did not statistically improve the EFS, but a trend was observed (44% versus 0%). Vincristine, Asta-Z or none purging did not show any significant effect on EFS (37% vs 32% vs 0%). On the contrary when the EFS was related to the site of relapse, isolated or sistemic, the difference was almost statistically significant (46% vs 18%). The analysis of our results indicates the isolated relapse as good prognostic factor in ABMT for ALL and high dose Vincristine associated to conditioning regimen as worthy of further investigations. PMID- 1855081 TI - An Italian study comparing allogeneic and autologous BMT in childhood acute lymphoblastic leukemia using HD-vincristine, F-TBI and cyclophosphamide. PMID- 1855084 TI - Bone marrow transplantation in childhood: a report from the AIEOP-BMT group registry. AB - A multicenter cooperative group has been activated in Italy in 1986, with the aim of focusing on the following issues: to standardize perspectively the approach to bone marrow transplantation (BMT) in pediatric centers granting the recommendations of the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP); to study effects and toxicity of preparative regimens to BMT; to evaluate the special features of BMT in children, such as clinical management, care and late effects, as peculiar issues of a pediatric setting. Indeed, one of the major aims of the group is to attempt to address in the most appropriate ways, such as in children only and at a nation-wide level, the most crucial questions about the real role of BMT, taking advantage from the fact that most of the children with cancer undergoing BMT in Italy have been treated homogeneously before transplant, i.e. according to AIEOP protocols (70%). Accordingly, specific information were recorded by means of problem oriented forms, aimed to generate a full registry. The registry has been collecting the experiences of 10 pediatric hematology and oncology centers where children eligible for BMT were registered and/or where BMT was performed. This paper was meant both to summarize the 4 years activity of the registry and to analyze what we have learnt so far, as well as what may be suggested to design our future strategies by presently available although retrospective data. It is concluded that the pediatric BMT registry we set up appears useful and of growing interest and potential relevance. PMID- 1855085 TI - The role of TBI in conditioning regimens for children. AB - TBI is currently used as a conditioning regimen in bone marrow transplantation (BMT) with various Radiation doses, fractionation scheduling and dose rate. In children, the most frequent neoplasms treated with TBI are leukemias and advanced Neuroblastoma (NB). In leukemias the radiation dose plays an important role, particularly in patients at high risk of relapse. In NB the inclusion of TBI in pretransplant therapy does not seem to produce any difference in survival. In pediatric patients TBI involved particular problems of technique dosimetry and toxicity. PMID- 1855086 TI - The role of thoraco-abdominal irradiation before marrow transplantation. PMID- 1855087 TI - Allogeneic bone marrow transplantation in children with acute leukemia: TBI is it necessary? PMID- 1855088 TI - Early infectious complications in children undergoing BMT. PMID- 1855089 TI - Impaired polysaccharide responses in immunodeficient patients: relevance to bone marrow transplant patients. AB - Bone marrow transplant patients are at increased risk for pneumococcal and H. influenzae type b (HIB) infections. These polysaccharide encapsulated bacteria are also pathogens for young healthy children. In healthy children age related susceptibility has been associated with poor response to polysaccharides and low serum IgG2 subclass antibody concentrations. Of note, immune reconstitution following bone marrow transplantation has been characterized by slow return of both the response to polysaccharides and IgG2 serum concentrations. Thus immune reconstitution following bone marrow transplantation is similar to the maturation that occurs in healthy children. In addition to transplant patients, we have identified five groups of immunodeficient patients who are at increased risk for polysaccharide encapsulated pathogens. IgG2 subclass deficient patients were shown to have impaired responses to polysaccharide antigens. We have also defined "Selective Antibody Deficiencies" which are individuals with normal IgG subclass concentrations but poor responses to polysaccharide antigens. Next, patients who developed HIB disease in spite of immunization (i.e. HIB vaccine failures) were demonstrated to have lower serum IgG2 and IgG4 subclass concentrations compared to controls. Finally, Native Americans (an ethnic group with an increased incidence of pneumococcal and HIB infections) were shown to be poor responders to polysaccharide antigens and have significantly lower concentrations of serum IgG2 and IgG4 as compared to controls. New HIB polysaccharide vaccines linked to protein antigens (conjugate vaccines) have been developed that are more immunogenic in healthy young children. In addition, these conjugate vaccines have resulted in protective responses in each of the newly described immunodeficient groups. We therefore now propose to evaluate bone marrow transplant patients' response to HIB conjugate vaccine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855090 TI - The role of the blood bank in bone marrow transplantation. PMID- 1855091 TI - Factors influencing remission post-BMT in patients with acute and chronic leukemia prepared with cyclophosphamide and total body irradiation (TBI). PMID- 1855092 TI - Role and perspectives of BMT in AML: the BFM experience. PMID- 1855093 TI - Allogeneic vs autologous BMT vs intensive chemotherapy in childhood AnLL during first complete remission: AIEOP experience. AIEOP Cooperative Group. AB - From 1982 to 1990, 340 children with newly diagnosed ANLL entered two consecutive AIEOP trials: LAM 8204 (1982-1987) and LAM 87 (1987-1990). Patients in both studies received identical remission induction with Daunorubicin and ARA-C. In the first study (LAM 8204) 167/171 patients were consolidated with four courses of DAT, followed by six additional courses of continuation therapy with three drug pairs given sequentially. Periodic intra-thecal ARA-C was used for CNS prophylaxis. For patients remaining on protocol, the OFS and EFS probability at 8 years was 35% and 30%, respectively. Induction response and EFS were adversely predicted by FAB MS subtype and hyperleukocytosis. In LAM 8204 trial there were 30 withdrawals represented by patients undergoing allogeneic (14) or autologous (16) BMT. For these patients the DFS probability at 5 years was 64% and 50%, respectively. On LAM-87 trial, 136/169 patients were evaluable and 98 (76%) attained CR. After consolidation with one course of DAT, patients with an HLA identical donor underwent allogeneic BMT and those lacking a matched donor were randomized to receive either autologous BMT or the LAM 8204 postremission chemotherapy. The 2-year probability of DFS for allografted patients was 76% significantly higher (P = 0.0001) than that observed for patients on chemotherapy (12%) or autologous BMT (31%) arms. PMID- 1855094 TI - Allogeneic bone marrow transplantation in children with ANL: Italian experience. AIEOP Group and the GITMO. PMID- 1855095 TI - ABMT for children AML: Italian experience. GITMO-AIEOP Groups. AB - We report data from an Italian survey on ABMT in 93 AML children less than 14 years in 1st or 2nd remission performed in 15 Centers. Different conditioning regimens have been employed: BAVC, an original schedule of chemotherapy; TBI plus Cy and/or other drugs (TBI + CHT); other high dose chemotherapy schedules (HD CHT). 62 patients have been transplanted in 1st CR; 38 have been conditioned with BAVC, 16 with TBI + CHT and 8 with HD CHT. Relapses were 21 in the BAVC group (DFS = 35% at 66 months), 5 in the TBI group (DFS = 61% at 48 months) and 5 in the HD CHT group; overall DFS is 39% at 66 months. 31 patients have been transplanted in 2nd CR; 14 were conditioned with BAVC and 16 with TBI + CHT; 6 patients relapsed in the first group, DFS is 56% at 50 months; in the second group 2 early deaths and 3 relapses occurred, DFS is 65% at 65 months. 1 patient in 2nd CR, conditioned with HD CHT, died during aplasia. Overall DFS is 59% at 65 months. Although no final conclusions concerning ABMT in AML children may be drawn from this retrospective study because of heterogeneity of population and methods, results obtained in 2nd CR are clearly better to those obtained with standard chemotherapy alone, confirming the role of ABMT in this high risk category of patients. PMID- 1855096 TI - Mismatched BMT in children. PMID- 1855097 TI - How to avoid bias when comparing bone marrow transplantation with chemotherapy. AB - It is important to know whether the survival of patients receiving an allogeneic bone marrow transplant (BMT) is better than that of patients receiving "conventional" treatment and, if BMT is better, to know how much better. Unfortunately, this information is surprisingly difficult to obtain accurately. Most studies that have attempted to define the value of BMT have been subject to varying degrees of bias because of the problems of identifying a "conventional chemotherapy" control group with which the outcome of patients who have received BMTs can be compared. A common bias arises when disease-free survival of BMT patients is compared with that of all other remitters. Early failures are then automatically assigned to the chemotherapy group even if they have donors and so would have gone on to a BMT had they not relapsed or died. Since some patients receive BMTs many months (or even years) after achieving remission-when their prognosis is already much improved-the definition of "early failure" is problematic. Nevertheless, although it is very rarely used, an adequate statistical method does exist to overcome this problem. Careful analysis cannot, however, overcome the problem of selection bias: patients selected for BMT are likely to have better (or worse) prognosis than patients who are treated conventionally. The only really satisfactory way of assessing the value of BMT is to conduct randomised trials comparing BMT with no BMT - or with extra chemotherapy. Several such studies are currently being undertaken assessing the role of autologous BMT in AML.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855098 TI - Bone marrow transplantation (BMT) in children with severe aplastic anemia (SAA) from donors other than HLA identical siblings. EBMT Working Party on Severe Aplastic Anemia. PMID- 1855099 TI - New developments in stem cell transplantation with special reference to the first in utero transplants in humans. AB - Based on the experience acquired in post-natal liver transplantation since 1974, we recently initiated pre-natal, in utero stem cell transplantation from the human fetal liver. The first two fetuses that we treated had immunodeficiencies, the third one had thalassemia major. Donors and recipients were not matched. The fetal cells were infused in the umbilical vein of the first two patients and injected intraperitoneally into the third one, under ultrasonic visualization. The first patient, born in 1988, has both engraftment of donor cells and reconstitution of cell-mediated immunity. This child, who had bare lymphocyte syndrome, has no clinical manifestation of the disease and he lives normally at home. The second child, born in 1989, has not yet developed a significant reconstitution of immunity although donor cell engraftment has been proven (Y chromosome in this female patient). The third patient has also evidence of donor cell take (Y chromosome in a female patient) but the effect on thalassemia has not yet been fully analyzed (donor hemoglobin present in small quantity). In all 3 cases, no side-effect of any kind developed in the mother nor in the fetus. Several advantages appear to be associated with in utero FLT: increased probability of graft take, ideal isolation of patient (in the uterus), optimal environment for fetal cell development (in the fetal host). PMID- 1855100 TI - HLA-mismatched bone marrow transplantation in thalassemia. PMID- 1855102 TI - Building a CE information base. PMID- 1855101 TI - Employee evaluation system. PMID- 1855103 TI - BMETs: the state of the profession. Interview by Michael Miller. PMID- 1855104 TI - A synopsis of current anesthesia machine design. PMID- 1855105 TI - A computerized purchase order management system. AB - Order processing and parts issuing are within the scope of an inventory management system and, as such, it was logical to incorporate the Purchase Order Management Menu into the biomedical engineering inventory management system. The Purchase Order Management function was implemented using the services of a biomedical engineering technician who is a staff member. Software development time (two months) was the only resource that was necessary to incorporate this function into the inventory system. This function, implemented on a PC, provided locally functions that had not been available on the mainframe-based hospital purchasing system. These functions directly addressed the needs of the users, who in this case are the staff members of the department of biomedical engineering at University Hospital, Stony Brook, New York. PMID- 1855106 TI - An evaluation of the DS-175, DS-145, and DS-115, digital blood pressure/pulse meter devices. AB - The performances of three electronic digital blood pressure/pulse meter models, Nissei DS-175, DS-145, and DS-115, were compared with measurements obtained using the mercury sphygmomanometer and auscultatory technique. Significant correlations (p less than 0.01) were found between the accepted medical criterion and the three models evaluated for both systolic (r = 0.64 to 0.74) and diastolic (r = 0.58 to 0.61) pressure measurements; however, the accuracies of the devices were deemed inadequate. The DS-175 was found to significantly overestimate both systolic (p less than 0.025) and diastolic (p less than 0.05) pressures. Furthermore, all models tended to overestimate low blood pressures, whereas high blood pressures were underestimated. Variables associated with home use by the lay person are also discussed. PMID- 1855107 TI - An electrocatalytic glucose sensor for in-vivo application. AB - An electrocatalytic sensor was developed for continuous measurement of glucose in circulating blood. The sensor is constructed as a flow-through cell that can be integrated into a blood vessel. The principle of measurement is based on the electrochemical oxidation of glucose at an active noble metal electrode. Selectivity is achieved by covering the sensing electrode with a diffusion limiting membrane and by analyzing the impedance of the electrode/membrane system. The real and the imaginary parts of the impedance at certain potentials are directly proportional to the glucose concentration in the blood. These parameters are used in calculating the blood glucose concentration. To test the sensor, an in-vivo experiment was conducted in a sheep. The sensor's performance remained reliable 71 days after its implantation. PMID- 1855108 TI - A probe for measuring current density during magnetic stimulation. AB - Time-varying magnetic fields induce currents in conductive media, and when the induced current is large enough in excitable tissue, stimulation occurs. This phenomenon has been applied to the human brain and peripheral nerves for diagnostic evaluation of the neural system. One important aspect that is presently unknown is the current level necessary in tissue for stimulation induced by magnetic fields. This study presents a method of measuring the induced current density from pulsed magnetic fields in vitro and in vivo. The current density probe was inserted into three concentrations of saline and into the brains of ten anesthetized cats. Two stimulation systems with coils 9 cm and 5 cm in diameter were used. The two systems provided sinusoidal and pulsatile coil currents. Measurements made in saline were compared with those calculated theoretically for a semi-infinite medium. The measured values were within 5% of the calculated values. Measurements made in the cat brain showed a 67% decrease compared with the theoretic model. This variance is attributed to the finite bounds of the skull. The results indicate that direct measurement of current density is possible. Subsequent measurements will aid in the design of improved magnetic stimulation systems. PMID- 1855109 TI - The electromagnetic compatibility standard for medical devices. PMID- 1855110 TI - Medical prefixes and suffixes. PMID- 1855111 TI - 5-Hydroxytryptamine-induced bronchoconstriction in the guinea-pig: effect of 5 HT2 receptor activation on acetylcholine release. AB - 1. The bronchoconstrictor responses to 5-hydroxytryptamine (5-HT) were studied in the guinea-pig to establish whether they are partly attributable to parasympathetic activation within the airways. 5-HT dose-response curves were constructed in anaesthetized and ventilated guinea-pigs pretreated with saline, or by bilateral cervical vagotomy or vagotomy plus atropine 3 mg kg-1, i.v. Vagotomy had no effect on 5-HT-induced bronchoconstriction but vagotomy plus atropine significantly reduced it. 2. To determine whether parasympathetic activation within the airways resulted from pre- or postganglionic stimulation, 5 HT dose-response curves were constructed for two groups of vagotomized guinea pigs treated with hexamethonium 2 mg kg-1, or hexamethonium 2 mg kg-1, plus atropine 3 mg kg-1. Guinea-pigs treated with hexamethonium plus atropine experienced significantly less 5-HT-induced bronchoconstriction than those treated with hexamethonium alone. 3. To characterize the subtype of 5-HT receptors involved in the activation of the parasympathetic system by 5-HT, dose response curves to 5-HT were constructed for four groups of vagotomized guinea pigs treated with saline, 1 mg kg-1 of the 5-HT3 antagonist ICS 205-930, or either 0.01 or 0.1 mg kg-1 of the 5-HT2 antagonist ketanserin. ICS 205-930 enhanced 5-HT-induced bronchoconstriction but 0.01 mg kg-1 ketanserin inhibited it significantly and 0.1 mg kg-1 ketanserin abolished it. To confirm the involvement of 5-HT2 receptors in these responses, we studied the effects in vagotomized guinea-pigs of atropine on the bronchoconstriction induced by the 5 HT2 agonist,x alpha-methyl-5-HT, infused at rates of 40 and 80ngkg-1s-'. At both rates, atropine significantly reduced the bronchoconstrictor responses to alpha methyl-5-HT. 4. The above results indicate that 5-HT-induced bronchoconstriction is indeed partly mediated by parasympathetic activation within the airways. This activation is mediated by stimulation of 5-HT2 receptors which are probably located on the postganglionic parasympathetic nerve endings. PMID- 1855112 TI - Investigation of the 5-hydroxytryptamine receptor mechanism mediating the short circuit current response in rat colon. AB - 1. 5-Hydroxytryptamine (5-HT) stimulated an increase in short-circuit current (SCC) in rat isolated colonic mucosa with an EC50 value of approximately 4 microM. The purpose of the present study was to investigate the 5-HT receptor mechanism(s) involved in this response. 2. The relatively selective 5-HT receptor agonists 5-carboxamidotryptamine (5-CT) and alpha-methyl-5-HT stimulated SCC and were 6 to 8 times less potent than 5-HT. 2-Methyl-5-HT was inactive both as an agonist and an antagonist. 3. The following compounds produced no significant inhibition of the SCC response to 5-HT: ketanserin (1 microM), methysergide (1 microM), methiothepin (0.3 microM), GR38032F (0.3 microM), tetrodotoxin (0.3 microM) and sulpiride (1 microM). 4. Both metoclopramide (3 and 10 microM) and cisapride (0.1 and 1 microM) inhibited the SCC responses to 5-HT in a concentration-related manner, and the higher doses similarly inhibited the responses to 5-CT. With both agonists the inhibitory effects of metoclopramide and cisapride were insurmountable. However, these inhibitory actions appeared to be selective since neither metoclopramide nor cisapride affected the basal SCC or the SCC response to prostaglandin E2. 5. The SCC responses to 5-HT and 5 methoxytryptamine were selectively inhibited by ICS205-930 at 3 microM, and respective pKB values of 6.0 and 6.6 were calculated. 6. It is concluded that 5 HT stimulates an SCC response in rat colon via a receptor mechanism that cannot be clearly identified as 5-HT1-like, 5-HT2 or 5-HT3. This receptor is selectively antagonized by ICS 205-930 and by the benzamides, metoclopramide and cisapride. The 5-HT receptor in rat colon therefore exhibits some of the properties associated with the so-called 5-HT4 receptor. PMID- 1855113 TI - Haemodynamic responses to NG-monomethyl-L-arginine in spontaneously hypertensive and normotensive Wistar-Kyoto rats. AB - 1. Nitric oxide (NO) is a major component of endothelium-derived relaxing factor (EDRF) the synthesis of which from L-arginine can be inhibited by NG-monomethyl-L arginine (L-NMMA). To assess whether basal NO tone is different in experimental hypertension, the haemodynamic effects of L-NMMA have been compared in anaesthetized spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats in which autonomic reflexes were blocked by ganglion blockade. 2. Bolus intravenous injections of L-NMMA, 1-30 mg kg-1, but not D-NMMA, 1-30 mg kg-1, induced dose-related increases in mean arterial pressure and decreases in conductances in the renal, carotid, hindquarters and mesenteric vascular beds in both SH and WKY rats. Although the different vascular beds varied in their maximum responses to L-NMMA, there were neither qualitative nor quantitative differences between the two rat strains in this respect. 3. The effects of L NMMA, 30 mg kg-1, i.v. on all parameters were rapidly and completely reversed by L-arginine, 30 mg kg-1, i.v., in both SH and WKY rats. 4. The results indicate that NO derived from L-arginine exerts a powerful vasodilator tone in both anaesthetized, ganglion-blocked SH and WKY rats. Although NO appears to contribute differentially to tone in the different vascular beds, there were no major differences between the two rat strains in this respect. Hence a reduced NO tone to the vasculature is unlikely to be a major factor contributing to the elevated blood pressure in the adult SH rat. PMID- 1855114 TI - Antagonism by reactive blue 2 but not by brilliant blue G of extracellular ATP evoked responses in PC12 phaeochromocytoma cells. AB - 1. The effects of reactive blue 2 and brilliant blue G, which have been shown to block extracellular ATP-evoked responses, were investigated to discover whether these compounds act as P2-purinoceptor antagonists in PC12 phaeochromocytoma cells. 2. Reactive blue 2 (10 to 100 microM) suppressed the ATP-stimulated dopamine secretion from PC12 cells in a dose-dependent manner. The concentration response curve for ATP was shifted to the right and the maximal response was decreased by reactive blue (30 and 100 microM). Brilliant blue G (up to 100 microM) did not significantly affect the secretion. 3. Reactive blue 2 (10 to 100 microM) suppressed the ATP-activated inward current recorded from the voltage clamped cells in a concentration-dependent manner. Brilliant blue G (up to 100 microM) did not affect the current. 4. The results suggest that reactive blue 2 but not brilliant blue G is a P2-purinoceptor antagonist in PC12 cells. The purinoceptors in these cells may be the same type as those involved in ATP-evoked smooth muscle relaxation, judging from the antagonism by reactive blue 2. PMID- 1855115 TI - A method for studying the pharmacodynamic profile of neuromuscular blocking agents on vocal cord movements in anaesthetized cats. AB - 1. A new in vivo experimental method is described whereby the neuromuscular blocking effects of muscle relaxants can be investigated on the intrinsic laryngeal muscles of anaesthetized cats. The peripheral tibialis anterior muscle preparation is employed in the same animal to compare the blocking effect on both preparations. 2. The intrinsic laryngeal muscles react with different sensitivities to the neuromuscular blocking agents when compared to the tibialis anterior muscle. 3. The neuromuscular response in both muscle preparations is similar with steroidal agents but appeared to be different after suxamethonium or isoquinoline analogues. 4. It is concluded that this preparation may become a useful tool for studying new muscle relaxants developed to facilitate rapid intubation conditions. PMID- 1855116 TI - Effect of the leukotriene receptor antagonists FPL 55712, LY 163443, and MK-571 on the elimination of cysteinyl leukotrienes in the rat. AB - 1. Leukotriene elimination via bile and urine is an important mechanism of inactivation for these potent lipid mediators. We investigated whether the elimination of cysteinyl leukotrienes is a target for the action of leukotriene receptor antagonists. 2. Experiments were performed in male rats under deep thiopentone anaesthesia. The bile duct and the urinary bladder were cannulated. Tritium labelled leukotrienes and leukotriene receptor antagonists were given via central venous catheters. Elimination of leukotrienes produced in vivo was studied following stimulation of endogenous leukotriene biosynthesis by operative trauma. 3H-leukotriene metabolites were identified by h.p.l.c. analysis. Leukotrienes produced in vivo were measured by combined use of h.p.l.c. and RIA. 3. Under control conditions, 49 +/- 12% of the injected 3H-leukotriene radioactivity was recovered in bile and 1 +/- 0.8% in urine within 90 min. Operative trauma resulted in initial hepatobiliary secretion of 887 +/- 206 pmol kg-1 h-1 of the endogenous leukotriene metabolite N-acetyl leukotriene E4 (LTE4NAc). 4. FPL 55712 strongly inhibited hepatobiliary elimination of 3H leukotriene radioactivity in a dose-dependent manner after i.v. injection of [3H] LTC4, [3H]-LTD4 or [3H]LTE4, respectively. Biliary [3H]-LTD4 was reduced most effectively. The leukotriene antagonist potently prevented biliary elimination of LTE4NAc produced in vivo. Bile flow and elimination from blood into bile of [3H] ouabain were also impaired by FPL 55712, but to a lesser extent. 5. LY 163443 reduced biliary [3H]-LTD4 after i.v. administration of [3H]-LTD4. However, the total elimination of 3H-leukotriene metabolites into bile was not significantly inhibited by the drug. 6. MK-571 reduced the biliary concentration of tracer after administration of 3H-leukotrienes most potently with respect to [3H]-LTD4. In contrast, the total recovery of 3H-leukotrienes in bile tended to increase. This is explained by a drug-induced increase in bile flow. 7. Urinary elimination of 3H-leukotrienes, quantitatively less important in the rat, was not significantly influenced by the leukotriene receptor antagonists. Recovery of 3H leukotriene radioactivity in liver and kidneys was quantitatively insignificant. 8. From our data, we conclude that leukotriene receptor antagonists have the potential to affect leukotriene elimination by a mechanism not necessarily related to receptor blockade. Inhibition of elimination by the receptor antagonists may prolong the biological half life of leukotrienes. This effect may counteract the antagonistic properties of these drugs. PMID- 1855117 TI - Convulsive thresholds in mice during the recovery phase from anaesthesia induced by propofol, thiopentone, methohexitone and etomidate. AB - 1. Convulsive thresholds were measured with intravenous pentylenetetrazol in mice during the recovery phase after intravenous anaesthetic doses of propofol (10 and 20 mg kg-1), thiopentone (30 mg kg-1), methohexitone (10 mg kg-1), and etomidate 3 mg kg-1). 2. The convulsive threshold rose after each agent, indicating an anticonvulsant action for all the drugs tested; this declined to control values with initial half times of: 1.56 min (propofol 10 mg kg-1); 1.03 min (propofol 20 mg kg-1): 1.02 min (methohexitone); 3.35 min (etomidate); 13.7 min (thiopentone). 3. At no time during the recovery phase of any agent did the convulsive threshold fall below control values, which might indicate an epileptogenic effect of the drug. 4. The threshold was depressed below control values by intravenous administration of Ro 15-4513, a partial inverse agonist at the benzodiazepine receptor, thus indicating the ability of this pentylenetetrazol test to demonstrate a proconvulsant effect. 5. We conclude that the abnormal movements or convulsions associated with recovery from anaesthesia with short-acting intravenous anaesthetics may not be the result of an intrinsic proconvulsant action of the drugs. PMID- 1855118 TI - The release of a non-prostanoid inhibitory factor from rabbit bronchus detected by co-axial bioassay. AB - 1. Methacholine relaxed phenylephrine-contracted aorta of the rat with the endothelium intact. This effect was inhibited by haemoglobin, methylene blue, gossypol, phenidone and L-NG-nitroarginine methyl ester (L-NAME). Rat aorta denuded of endothelium failed to relax in response to methacholine, histamine and the peptidoleukotrienes C4, D4 and E4. 2. Methacholine and histamine but not leukotrienes C4, D4 and E4 relaxed phenylephrine-contracted rat aorta without endothelium when surrounded by rabbit epithelium-intact bronchus. The muscarinic antagonist atropine antagonized the methacholine-induced relaxation. 3. Removal of the epithelium either mechanically or chemically, abolished methacholine induced relaxation of rat aorta in the co-axial bioassay. These data indicate that the epithelium is responsible for the observed relaxant effect to methacholine and histamine. 4. The cyclo-oxygenase inhibitor, indomethacin, the phospholipase A2 inhibitor, mepacrine and the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), failed to inhibit methacholine-induced relaxation of rat aorta in the co-axial bioassay. This indicates that the epithelium-derived inhibitory factor (EpDIF) is not a product of the cyclo oxygenase or lipoxygenase pathway or a product derived from activation of phospholipase A2. 5. Haemoglobin, methylene blue, phenidone, gossypol and L-NAME failed to inhibit the relaxation of rat aorta in the co-axial bioassay. These results demonstrate that EpDIF detected in the co-axial bioassay is not endothelium-derived relaxing factor (EDRF) or nitric oxide. Similarly, catalase was without effect. 6. EpDIF is unlikely to be a peptide since papain and alpha chymotrypsin failed to alter the methacholine-induced relaxation of rat aorta in the co-axial bioassay. Furthermore, thiorphan, captopril and aprotinin were also without effect, suggesting that EpDIF is not a substrate for airway peptidases. 7. The results presented in this paper demonstrate the release of a vasoactive epithelium-derived inhibitory factor (EpDIF) from rabbit intrapulmonary bronchi by use of a co-axial bioassay preparation. PMID- 1855119 TI - Effects of helospectin I on insulin and glucagon secretion in the mouse. AB - 1. The helospectins are peptides structurally related to helodermin, vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI) and secretin, which all potently stimulate glucagon secretion in the mouse. Therefore, the effects of helospectin I (0.1-0.8 nmol kg-1) on insulin and glucagon secretion under basal conditions and after stimulation with glucose (2.8 mmol kg-1) or the cholinoceptor agonist, carbachol (0.16 mumol kg-1), were examined in vivo in the mouse. 2. Helospectin I potently increased plasma levels of glucagon after its intravenous injection in mice. The increase was observed after only 2 min, and was evident also after 6 min. 3. In contrast, plasma insulin levels were not altered by helospectin I after 2 min, but slightly increased after 6 min. Plasma glucose levels were not altered by the peptide. 4. Carbachol-induced glucagon secretion was markedly potentiated by helospectin I. In contrast, glucose- or carbachol-stimulated insulin secretion was not affected by the peptide. 5. In conclusion, helospectin I markedly stimulates glucagon secretion in the mouse whereas the peptide has no direct action on insulin secretion. This pattern of effect of helospectin I is similar to that previously reported for helodermin, VIP, PHI and secretin in the mouse, i.e., for all peptides belonging to this superfamily of peptides. PMID- 1855120 TI - Characterization of Gaddum's substance R. AB - 1. When the isolated small intestine of the rat is perfused via the mesenteric artery, an oxytocic principle (Gaddum's substance R) is released which is detectable in the perfusate after 30 min and is present in samples collected 8 h later. 2. The oxytocic activity of substance R is lost after boiling but is unaffected by treatment with thioglycolate. Furthermore, atropine, methysergide and indomethacin failed to antagonize uterine contractions to substance R. 3. Neither substance R nor urinary kallikrein alone induce a contraction of the guinea-pig isolated ileum. However, in the presence of kininogen both substance R and urinary kallikrein produce a slow and prolonged contraction of the guinea-pig ileum. 4. The oxytocic and kininogenase properties of both substance R and urinary kallikrein are inhibited by Trasylol. 5. Soy bean trypsin inhibitor (SBTI) selectively inhibited both the oxytocic and the kininogenase activities of substance R but not those of urinary kallikrein. 6. Gel filtration of substance R resolved a single peak of oxytocic activity with an estimated molecular weight of 40 kDa. 7. We conclude that substance R is a kininogenase enzyme which may be distinguished from plasma kallikrein by its molecular weight and from urinary kallikrein by its susceptibility to SBTI. The exact nature of this enzyme remains to be elucidated. PMID- 1855121 TI - Effects of hyperosmolarity on human isolated central airways. AB - 1. We studied the effect of hyperosmolarity on human isolated airways because a better understanding of the effect of hyperosmolarity on the human airway wall may improve insight into the pathophysiology of hyperosmolarity-induced bronchoconstriction in asthma. 2. In cartilaginous bronchial rings dissected from fresh human lung tissue, hyperosmolar krebs-Henseleit buffer (450 mosM, extra sodium chloride added) evoked a biphasic response: a rapid relaxation phase (peak after 5.0 +/- 0.3 min) followed by a slow contraction phase (peak after 25.4 +/- 0.8 min). 3. With the histamine (H1) receptor antagonist mepyramine, the contraction phase was reduced to 41.2% of the control value (P less than 0.001), with atropine to 50.0% (P less than 0.01), with the local anaesthetic lignocaine to 48.7% (P less than 0.05) and with mepyramine together with atropine to 19.2% (P less than 0.001). 4. With the inhibitor of neutral metalloendopeptidase, phosphoramidon, the contraction phase increased to 128.0% of the control value (P less than 0.05) and after removal of the epithelium to 131.8% (P less than 0.05). 5. Indomethacin, the leukotriene C4/D4 (LTC4/D4) antagonist FPL 55712 or the blocker of nerve conduction, tetrodotoxin, had no effect on the contractile phase. 6. The relaxation phase was not altered by any of these drugs nor by epithelial denudation. The relaxation phase was also unchanged in the presence of alpha-chymotrypsin, which degrades muscle relaxing peptides such as vasoactive intestinal peptide. 7. Hyperosmolar buffer slightly increased the sensitivity and maximal response to methacholine as well as the cholinergic twitch to electric field stimulation. 8. We conclude that hyperosmolarity releases acetylcholine, histamine and neuropeptides in the human airway wall in sufficient quantities to contract airway smooth muscle. This release itself or its effect on airway muscle is modulated by the airway epithelium. The mechanism of the relaxation phase may be an unknown smooth muscle relaxing substance or a direct effect on the airway muscle, related to ion fluxes. PMID- 1855122 TI - Characterization of the 5-HT receptor mediating endothelium-dependent relaxation in porcine vena cava. AB - 1. 5-Hydroxytryptamine (5-HT) relaxes rings of neonatal porcine isolated vena cava by both an endothelium-dependent and an endothelium-independent mechanism. The receptor mediating the latter response has been shown to be a 5-HT1-like receptor (positively coupled to adenylyl cyclase) located on the vascular smooth muscle. The features of the endothelium-dependent response to 5-HT in this preparation are now described. 2. In ring preparations contracted with the stable thromboxane-A2-mimetic, U-46619 (10 nM), and in the presence of the 5-HT2 receptor antagonist ketanserin (1 microM), low concentrations of 5-HT (1-100 nM) evoked an endothelium-dependent, rapid, 'spike-like' relaxation. Higher concentrations of 5-HT (0.1-10 microM) elicited a more sustained, but endothelium independent relaxation. 3. Relaxation induced by low concentrations (1-100 nM) of 5-HT was abolished by endothelium removal, and was markedly (but not totally) inhibited by the guanylate cyclase inhibitor, methylene blue (10 microM) or by the inhibitor of endothelium-derived nitric oxide (NO) synthesis, L-NG monomethylarginine (L-NMMA; 100-500 microM). 4. The endothelium-dependent response to 5-HT was mimicked by alpha-methyl-5-HT, 5-methoxytryptamine, tryptamine and 2-methyl-5-HT, but not by sumatriptan or 8-hydroxy-di-n propylaminotetralin (8-OH-DPAT) at concentrations up to 10 microM. In contrast, relaxation evoked by 5-carboxamidotryptamine (5-CT) was endothelium-independent. 5. The endothelium-dependent relaxation induced by 5-HT or alpha-methyl-5-HT was antagonized by methysergide, methiothepin, cyproheptadine and metergoline, but not by ketanserin, spiperone, ondansetron, verapamil, cyanopindolol, mesulergine, ICS 205-930, or indomethacin. 6. These results suggest that the endothelium dependent relaxation of porcine vena cava induced by 5-HT is largely mediated by the release of NO (although other endothelium-derived relaxing factors may also be involved) and that 5-HT is acting at a receptor which is not '5-HT1-like', 5 HT2, 5-HT3 or 5-HT4 and is not comparable to recognised 5-HT receptor ligand binding sites. The characteristics of this receptor are discussed in relation to the endothelial 5-HT receptor types in other blood vessels. PMID- 1855123 TI - Interactions between the vascular peptide endothelin-1 and sensory neuropeptides in gastric mucosal injury. AB - 1. The interactions between endogenous and exogenous sensory neuropeptides on gastric mucosal injury induced by endothelin-1 (ET-1) have been investigated in the anaesthetized rat. 2. Close intra-arterial infusion of ET-1 (4-20 pmol kg-1 min-1) dose-dependently induced vasocongestion and haemorrhagic necrosis in the gastric mucosa. 3. Capsaicin-pretreatment, two weeks earlier to deplete sensory neuropeptides from primary afferent neurones, augmented the mucosal damage induced by ET-1, as assessed by both macroscopic and histological examination. 4. The damage induced by threshold doses of ET-1 alone or in capsaicin-pretreated rats was further enhanced by administration of indomethacin (5 mg kg-1, i.v.), indicating a modulatory influence of endogenous prostanoids. 5. Morphine administration (3 mg kg-1, i.v.), which can prevent neuropeptide release, augmented the damage induced by threshold doses of ET-1, this effect being reversed by naloxone (1 mg kg-1, i.v.). 6. Concurrent local intra-arterial infusion of rat alpha-calcitonin gene-related peptide (10-50 pmol kg-1 min-1) dose-dependently reduced the mucosal injury induced by ET-1. 7. These findings suggest interactions between ET-1 and sensory neuropeptides, which may reflect an important influence of these peptide mediators in the regulation of mucosal integrity. PMID- 1855124 TI - A selective effect of protein kinase C activators on noradrenaline release compared with subsequent contraction in canine isolated saphenous veins. AB - 1. Effects of protein kinase C (PKC) activators and inhibitors on both tritium overflow and subsequent contraction evoked by transmural nerve stimulation (TNS) were investigated in canine saphenous veins prelabelled with [3H]-noradrenaline. 2. Activation of PKC by stepwise increasing concentrations (0.01 nM-1 microM) of 12-O-tetradecanoylphorbol 13-acetate (TPA), phorbol 12,13-dibutyrate (PDBu) or mezerein caused a significant and concentration-dependent enhancement of the tritium overflow evoked by TNS, while the activators failed to affect the corresponding contraction except with the highest concentration of PDBu when the contraction was significantly reduced. Phorbol, which is inactive on PKC, had no effects on the tritium overflow and contraction induced by TNS. 3. PKC inhibitors, polymyxin B (1 and 10 microM) and the isoquinolinesulphonamide, H-7 (1 microM), inhibited significantly the phorbol ester-potentiated tritium overflow evoked by TNS with no effects on the contraction. H-7 and the related inhibitor H-8 at 10 microM reduced significantly both responses to TNS in the presence of TPA, while they suppressed only the TNS-induced contraction in the absence of TPA. 4. None of the PKC activators or inhibitors affected the spontaneous tritium overflow. 5. PDBu (0.01 and 0.1 microM) elevated resting tension of the veins more effectively than TPA and mezerein. 6. These results suggest that PKC may modulate electrically stimulated noradrenaline release from adrenergic nerve endings of the canine saphenous veins and the PKC activators may act more selectively on presynaptic than postsynaptic sites, but have no apparent effect on postjunctional noradrenergic mechanisms. PMID- 1855125 TI - The involvement of endothelium-derived relaxing factor in the regulation of renal cortical blood flow in the rat. AB - 1. In the present study the role of endogenous nitric oxide (NO) was investigated, in the regulation of renal cortical blood flow (RCBF) in vivo in anaesthetized rats under conditions in which prostacyclin involvement had been eliminated. 2. Infusions of the NO synthesis inhibitor NG-monomethyl-L-arginine (MeArg) at 1 or 3 mg kg-1 min-1, i.v., produced significant decreases in RCBF of 29 +/- 7% and 35 +/- 5%, respectively. These effects were reversed by co-infusion of a 3 fold excess of L-arginine (L-Arg). 3. Similarly, intravenous infusion of N omega-nitro-L-arginine methyl ester (NO2Arg) at 30 or 300 micrograms kg-1 min-1 attenuated RCBF by 21 +/- 4% or 53 +/- 4%, respectively, and these effects were reversed by L-Arg (3 or 10 mg kg-1 min-1, i.v.). Most importantly, a low dose of NO2Arg (30 micrograms kg-1 min-1, i.v.), while having no pressor effect, considerably reduced RCBF, indicating that basal release of NO is important for the maintenance of renal cortical blood flow. 4. MeArg (3 mg kg-1 min-1, i.v.) or NO2Arg (300 micrograms kg-1 min-1, i.v.) inhibited endothelium-dependent acetylcholine (ACh, 10 micrograms kg-1 min-1, i.v. for 3 min) increases in RCBF in an L-Arg reversible manner, but did not affect endothelium-independent (dopamine 10 micrograms kg-1 min-1, i.v., for 3 min) increases. Endothelin- 1 (1 nmol kg-1, i.v.), when given as a control for the vasoconstrictor effects of MeArg and NO2Arg, produced a slight inhibition of the ACh-induced increase in RCBF, but this effect was significantly weaker than that produced by MeArg or NO2Arg. 5. Our findings suggest that MeArg and NO2Arg inhibit basal and ACh stimulated release of NO in the renal cortical vasculature. Thus, endogenous NO formation may play an important role in the local regulation of renal cortical blood flow. PMID- 1855126 TI - Flosequinan, a vasodilator with a novel mechanism of action. AB - 1. The mechanism of action of flosequinan was investigated in ferret aortic smooth muscle by the simultaneous measurement of aequorin luminescence and isometric force. 2. The control calcium-force curve was obtained by plotting the calibrated aequorin luminescence against the force from potassium-depolarized muscles. Flosequinan relaxed potassium-depolarized muscles by causing parallel changes in [Ca2+]i and force with no shift in the control [Ca2+]i-force relationship. 3. The [Ca2+]i-force relationship in the presence of a maximally effective concentration of phenylephrine was significantly shifted to the left of that for the control, potassium-depolarized muscle. Flosequinan relaxed the phenylephrine-contracted muscle by causing a large decrease in force with only a minimal decrease in [Ca2+]i, resulting in an apparent rightward shift of the [Ca2+]i-force relationship, toward the control curve. 4. In comparison, sodium nitroprusside caused relaxation of either the potassium- or phenylephrine-induced contraction solely by a decrease in [Ca2+]i with no shift in either calcium-force relationship. 5. Milrinone caused no significant rightward shift of the calcium force relationship during phenylephrine- or potassium-induced contractions, but when milrinone was added in the absence of vasoconstrictors, relaxation was obtained with no significant decrease in [Ca2+]i. 6. Flosequinan appears to differ in mechanism of action from both nitroprusside and milrinone. It relaxes depolarization-mediated contractions solely by decreasing [Ca2+]i but also appears to be capable of reversing the apparent calcium sensitizing action of phenylephrine. PMID- 1855127 TI - The contribution of Rb-permeable potassium channels to the relaxant and membrane hyperpolarizing actions of cromakalim, RP49356 and diazoxide in bovine tracheal smooth muscle. AB - 1. Cromakalim (1 and 10 microM), RP49356 (5 and 50 microM) and diazoxide (100 and 300 microM) produced full relaxation of smooth muscle strips pre-contracted with 25 mM KCl. These agents caused membrane hyperpolarization and increased 42K and 86Rb efflux. The time taken to achieve the maximum change in each of these parameters (tmax) was less for the higher concentration levels of cromakalim, RP49356 and diazoxide than for the lower concentration levels. 2. Calculation of permeability (P) changes showed that cormakalim (1 and 10 microM) produced a greater rise in PK than PRb, although the PRb:PK ratio was similar at both concentration levels. Similarly RP49356 produced a greater change in PK than PRb. However, in contrast to cromakalim, this difference was more marked at the higher concentration (50 microM) and was reflected by a differential effect of the two concentrations of RP49356 on the PRb:PK ratio. Diazoxide (100 and 300 microM) produced similar changes in PK and PRb. 3. For cromakalim (1 and 10 microM) the tmax for the electrical and mechanical effects and also the profile of change in these parameters corresponded to changes in both PK and PRb. For RP49356 (5 microM), changes in tension and membrane potential were related to both changes in PK and PRb, whereas at 50 microM these responses more closely corresponded to changes in PK. For diazoxide (100 and 300 microM) the electrical and mechanical effects corresponded to changes in both PK and PRb. 4. The results show that changes in 42K and 86Rb efflux induced by cromakalim, RP49356 and diazoxide are good indicators of changes in membrane PK and PRb evoked by these agents. Furthermore, it is concluded that the K channels involved in the mechanical and electrical effects of cromakalim are represented by the opening of a single population through which Rb can pass less easily than K, whilst the K channels associated with actions of diazoxide are equally permeable to both K and Rb. In contrast, the relaxant and membrane hyperpolarizing actions of RP49356 may involve the opening of more than one group of K channels which differ in their permeability to Rb. PMID- 1855128 TI - Facilitation of amphetamine-induced hypothermia in mice by GABA agonists and CCK 8. AB - 1. Amphetamine-induced hypothermia in mice is facilitated by dopaminergic stimulation and 5-hydroxytryptaminergic inhibition. The present study was designed to investigate: (a) the involvement of other neuronal systems, such as the gamma-aminobutyric acid (GABA), the opioid and the cholecystokinin (CCK-8) systems; (b) the possible contribution of hydroxylated metabolites of amphetamine to the hypothermia; (c) the capacity of dopamine itself to induce hypothermia and its mechanisms, in order to clarify the resistance of amphetamine-induced hypothermia to certain neuroleptics. 2. Pretreatment with the GABA antagonists, bicuculline and picrotoxin, did not inhibit amphetamine-induced hypothermia. The GABAB agonist, baclofen (2.5 mg kg-1, i.p.) potentiated this hypothermia, whereas the GABAA agonist, muscimol, did not. gamma-Butyrolactone (GBL) (40 mg kg-1, i.p.) and the neuropeptide CCK-8 (0.04 mg kg-1, i.p.) also induced potentiation. The opioid antagonist, naloxone, was without effect. 3. Dopamine itself (3, 9, 16 and 27 micrograms, i.c.v.) induced less hypothermia than the same doses of amphetamine. Sulpiride did not block dopamine-induced hypothermia, but pimozide (4 mg kg-1, i.p.), cis(z)flupentixol (0.25 mg kg-1, i.p.) and haloperidol (5 micrograms, i.c.v.) did. The direct dopamine receptor agonist, apomorphine, did not alter the hypothermia. Neither the 5-hydroxytryptamine (5-HT) receptor blocker, cyproheptadine, nor the inhibitor of 5-HT synthesis, p chlorophenylalanine (PCPA), modified dopamine-induced hypothermia. Fluoxetine, an inhibitor of 5-HT reuptake, had no effect, whereas quipazine (6 mg kg-1, i.p.), a 5-HT agonist, totally prevented the hypothermia. Hypothermia was unaffected by pretreatment with CCK-8. 4. These data indicate that the hypothermia induced by amphetamine involves not only dopaminergic and 5-hydroxytryptaminergic systems which are functionally antagonistic, but is also facilitated by direct or indirect GABA and CCK-8 receptor stimulation. This facilitation could result, in part, from modulation of dopaminergic neurotransmission. This may explain the apparent resistance of amphetamineinduced hypothermia to some neuroleptics, while dopamine-induced hypothermia is not resistant. The possible action of hydroxylated metabolites of amphetamine may also help to explain these differences. PMID- 1855129 TI - Blood pressure and vascular reactivity changes in spontaneously hypertensive rats fed fish oil. AB - 1. To examine possible mechanisms of antihypertensive effects of feeding fish oil rich in n-3 fatty acids, we have studied vascular reactivity of aortic rings and perfused mesenteric resistance vessels of spontaneously hypertensive rats (SHR) given such a diet. 2. In two experiments, rats were fed a semi-synthetic diet containing either 'fish oil' (10 and 20% by weight) or hydrogenated coconut oil (control) (10 and 20%) for 4 weeks. 3. Blood pressure rose significantly less in the fish oil group than in controls in both experiments. 4. Aortic rings from control rats showed endothelium-dependent relaxations to low concentrations of acetylcholine (ACh) but relaxed less at higher concentrations. In contrast, rings from the fish oil group had relaxations which increased through the range of concentrations used. Indomethacin (10 microM) also increased the relaxation responses seen in rings from control rats, suggesting that fish oil inhibits a contractile cyclo-oxygenase product. This contractile substance may be thromboxane A2 (TxA2) or its endoperoxide precursor, prostaglandin H2 (PGH2) as aortic incubates and serum levels of TxB2 (the stable product of TxA2) were greatly reduced in fish oil-fed rats, and the decrease of relaxant responses to high concentrations of ACh were also blocked by a TxA2/PGH2 receptor blocker (SQ 29548). 5. In contrast to aortic rings, perfused preconstricted mesenteric resistance vessels of control rats relaxed to ACh in a similar fashion to tissues from fish oil-fed rats. However, in this preparation, fish oil feeding enhanced relaxations to sodium nitroprusside (SNP) and contractile responses to noradrenaline were less than controls. After removal of endothelium with 0.05% saponin, contractile responses to noradrenaline increased in both groups but responses from fish oil-treated rats were still attenuated. This suggests that fish oil feeding alters reactivity of mesenteric resistance vessels at the level of the smooth muscle. 6. The results indicate that fish oil feeding may reduce blood pressure by decreasing vascular smooth muscle reactivity to noradrenaline in resistance vessels. The effect may be enhanced by inhibition of an endothelium derived cyclo-oxygenase product, such as TxA2 or PGH2 in conduit vessels. PMID- 1855130 TI - The mechanism of the sympathoinhibitory action of urapidil: role of 5-HT1A receptors. AB - 1. An investigation was carried out to determine if the sympathoinhibition caused by urapidil is due to activation of 5-HT1A receptors by investigating whether it could be reversed by the non-selective 5-HT1A receptor antagonist spiperone. To control for the possibility of functional antagonism by spiperone, the ability of spiperone to reverse the sympathoinhibition caused by clonidine was also investigated. These experiments were carried out in anaesthetized prazosin pretreated cats to prevent the alpha 1-adrenoceptor antagonist action of urapidil and spiperone from masking any effects observed. 2. Cats were anaesthetized with alpha-chloralose and simultaneous recordings were made of whole cardiac, splanchnic and renal nerve activities, blood pressure, heart rate and femoral arterial flow (from which conductance was derived). All animals were initially pretreated with prazosin (1 mg kg-1, i.v.) given in divided doses (0.75 followed 10 min later by 0.25 mg kg-1), then either urapidil (0.75 mg kg-1, i.v.) or clonidine (10 micrograms kg-1, i.v. in two divided doses) followed by 3 separate injections of spiperone (1 mg kg-1, i.v.). In another set of experiments urapidil was given followed by injections of the appropriate vehicle for spiperone, while in another set urapidil was replaced with an injection of the appropriate vehicle followed by injections of spiperone. In the experiments with clonidine, the alpha 2-adrenoceptor antagonist Wy 26392 (0.3 mg kg-1) was given after the last injection of spiperone. 3. The prazosin pretreatment caused a fall in blood pressure associated with femoral vasodilatation, a small bradycardia and little change in cardiac, splanchnic or renal nerve activities. Urapidil or clonidine injection after prazosin caused sympathoinhibition associated with an additional bradycardia. However, only urapidil caused an additional fall in blood pressure. Spiperone injections reversed the sympathoinhibition caused by urapidil but not that caused by clonidine. The sympathoinhibition caused by clonidine was reversed by the alpha 2-adrenoceptor antagonist Wy 26392. 4. These results show that the sympathoinhibition caused by urapidil in prazosin-pretreated cats can be reversed by spiperone. The reversal of this sympathoinhibition is not due to functional antagonism. It is concluded that urapidil can cause sympathoinhibition by activation of 5-HTlA receptors. PMID- 1855131 TI - Learning disturbances following excitotoxic lesion of cholinergic pedunculo pontine nucleus in the rat. AB - Compared to brain anterior cholinergic systems such as the septo-hippocampal and nucleus basalis-cortical pathways, posterior cholinergic groups have received little attention with respect to their involvement in learning and memory. In this study, the effect of lesion of the cholinergic pedunculo-pontine cell bodies (PPN) by the excitotoxin quisqualic acid was investigated on spontaneous locomotor activity and learning in rats. Behavioral tasks designed to test both reference memory (cross maze and water maze) or working memory (radial maze) were used. PPN lesion had no effect on initial nor on nocturnal locomotor activity in a circular corridor. The lesion disrupted learning in the water and radial mazes, but was without influence on acquisition in the cross maze. The difference in results obtained in the two tasks designed to test reference memory (cross maze and water maze) indicated that the disturbance depended on task difficulty rather than on a particular memory component. It is suggested that the PPN is involved in the sustained attention required to perform correctly in water and radial mazes. The PPN cannot therefore be considered as a uniquely extrapyramidal structure. In addition to its descending outputs, the PPN has ascending connections to the neocortex, either directly or indirectly via the thalamus, and so pathological changes in this region may be partly responsible for the cognitive disorders of aging or those observed in various neurodegenerative conditions. PMID- 1855132 TI - Memory facilitation by post-training intraperitoneal, intracerebroventricular and intra-amygdala injection of Ro 5-4864. AB - Post-training i.p. (2.0 or 5.0 mg/kg), i.c.v. (2.5 micrograms/rat), or intra amygdala (1.6-40 ng/amygdala) administration of Ro 5-4864 causes memory facilitation of step-down inhibitory avoidance in rats. The effect is expressed as an increased latency to step down in a retention test carried out 24 h after training. Ro 5-4864 is a blocker of the Cl(-)-channel associated with GABAA receptors, at a site sensitive to the antagonist, PK11195, and different from that sensitive to picrotoxin. PK11195, given i.c.v. (2.5 micrograms/rat) or into the amygdala (8 ng/amygdala), antagonized the effect of Ro 5-4864. Intra-amygdala picrotoxin administration (80 ng/amygdala) also caused retrograde memory facilitation, but its effect was not antagonized by PK11195. At a higher dose (40 ng/amygdala), PK11195 had an amnestic effect of its own, which suggests that it might be acting against an endogenous ligand of receptor to Ro 5-4864 in the Cl( )-channel. These findings support the hypothesis that there is a GABAA mechanism in the amygdala normally involved in the modulation of the post-training memory processing of aversive learnings. PMID- 1855133 TI - Enterostatin suppresses food intake following injection into the third ventricle of rats. AB - The effect on food intake of an activation peptide from pancreatic pro-colipase, called enterostatin, has been studied after parenteral or third ventricular administration. The activation peptide (enterostatin = Val-Pro-Asp-Pro-Arg = VPDPR) reduced food intake when given intraperitoneally. Low doses of this peptide also reduced food intake when given into the third ventricle, but high doses were ineffective. Enterostatin did not modify the stimulatory effects on food intake of clonidine, an alpha 2-adrenergic agonist, suggesting that its anorectic effects are not mediated via the alpha 2-adrenergic system. These data suggest that enterostatin, an activation peptide from pro-colipase, may play a role in producing satiety. PMID- 1855134 TI - Soma diameter and oxidative enzyme activity of identified alpha-motoneurons: application of a retrograde fluorescent neuronal tracer. AB - Using a fluorescent compound as a retrograde neuronal tracer for the identification of a specific motoneuron pool, we examined the soma diameter and oxidative enzyme activity of alpha-motoneurons innervating the extensor digitorum longus (EDL) and the soleus (Sol) muscles in the rat. An inverse relationship between soma diameter and oxidative enzyme activity was demonstrated in the EDL, while there was no significant relationship between these variables in the Sol. These results suggest that an inverse relationship between soma diameter and oxidative enzyme activity cannot always be demonstrated in all of the motoneuron pools. PMID- 1855135 TI - Elicitation of hippocampal theta by intraseptal carbachol injection in freely moving rats. AB - Following infusion into the septum of carbachol, a powerful muscarinic agonist, a theta (theta) rhythm was emitted during complete relaxed immobility as well as during automatic movements. This was not seen following administration of the drug within the caudate/putamen, which is rich in muscarinic receptors but which is not believed to be involved in hippocampal theta generation. Local administration of atropine abolished carbachol-induced theta but did not suppress the theta which normally occurs during voluntary movements. These findings clearly demonstrate that at least a component of the hippocampal theta may be manipulated by intraseptal administration of muscarinic agents, thus supporting our previous assumption that, in theta generation, the septum may be a sensitive site of action for exogenously administered cholinomimetic drugs. They also raise the possibility that the activity of the well identified septohippocampal system involved in the presumed cholinergic hippocampal theta generation is regulated trans-synaptically by acetylcholine at the septal level. Finally, our micropharmacological approach, by suggesting the carbachol-responding septohippocampal cells pacing theta rhythm which is correlated to important functional states, such as attentive waking and active sleep, provides a potential powerful tool for clarifying the neurobiological function of the septohippocampal pathway. PMID- 1855136 TI - An intracellular recording study of stimulus-specific response properties in cat area 17. AB - Stimulus-specific response properties, such as direction or orientation selectivity, were studied intracellularly in cells recorded from area 17 of the cat. In all 5 direction selective complex cells and one orientation selective simple cell successfully studied, visually evoked excitatory postsynaptic potentials (EPSPs) were tuned to the preferred direction or orientation. Visually evoked inhibitory postsynaptic potentials (IPSPs) were also tuned to the preferred direction/orientation of stimulus. IPSPs evoked by the non-preferred stimulus when present were smaller than those evoked by the preferred stimulus. IPSPs were undetected in two of the 5 cells tested. These results suggest that directionally/orientationally tuned EPSPs make a major contribution to stimulus specificity in visual cortical neurons but IPSPs evoked by a stimulus with null direction/orientation may sharpen the stimulus specificity. PMID- 1855138 TI - Circadian differences in neuronal activity of the suprachiasmatic nucleus in brain slices prepared from photo-responsive and photo-non-responsive Djungarian hamsters. AB - The suprachiasmatic nucleus (SCN) of the hypothalamus, as the putative generator of circadian rhythmicity, plays an important role in mammalian photoinduction. To determine if SCN function differs in photo-non-responsive Djungarian hamsters, we defined the pattern of spontaneous neuronal discharge of single cells from SCN slices in vitro of photo-responsive and photo-non-responsive phenotypes. Responsive hamsters exhibited a peak neuronal discharge rate (4.8 +/- 0.5 Hz) during the mid day which gradually attenuated through the late day and early night. In non-responsive hamsters, a similar discharge rate (5.1 +/- 0.5) was maintained through the late day and early night. The delayed decline in spontaneous firing rate of non-responders correlates with their delayed activity onset and delayed nocturnal pineal melatonin pulse. These data support the argument that the absence of photoperiodic adjustments in Phodopus sungorus rests with differences in SCN function. PMID- 1855137 TI - Noradrenaline release in the rat amygdala is increased by stress: studies with intracerebral microdialysis. AB - The effects of immobilization and tail-pinch stress on extracellular noradrenaline (NA) release in the amygdala were studied in freely moving rats with intracerebral microdialysis techniques. After collection of basal levels of NA (2.63 +/- 0.26 pg/50 microliters/20 min), the rat was exposed to either immobilization stress or tail-pinch stress for 20 min. Immobilization and tail pinch stress increased NA release to 250 and 243% of basal levels, respectively and the elevation of NA release was observed for 60 min and 40 min after release from stress, also respectively. These data suggest that microdialysis is a useful way to study extracellular NA release in the amygdala and that NA neurons in this region are activated by both immobilization and tail-pinch stress. PMID- 1855139 TI - Periaqueductal gray matter and nucleus raphe magnus involvement in anterior pretectal nucleus-induced inhibition of jaw-opening reflex in rats. AB - In previous studies we have shown that electrical stimulation of the cortex or anterior pretectal nucleus (APT) inhibits the jaw-opening reflex (JOR). In the present study we investigated whether these effects are mediated by a relay in the periaqueductal gray matter (PAG) or rostroventromedial medulla (RVM). Experiments were performed on chloralose-urethane anesthetized rats. The JOR which was elicited by electrical stimulation of the mandibular incisor tooth was monitored by recording the evoked digastric muscle activity. Conditioning stimulation (20 ms train of 0.2 ms pulses at 400 Hz) was delivered to the facial area of the sensorimotor cortex, APT, PAG or nucleus raphe magnus (NRM) 50 ms prior to the test stimulus to the tooth that evoked the JOR. In addition, the effects of microinjections of glutamate into APT, PAG and NRM on the tooth-evoked JOR were also evaluated. The inhibition of the JOR by electrical and glutamate conditioning stimulation was found to be most potent for activation of the NRM and least potent for the APT. Local anesthetic (2% lidocaine, 0.3-0.6 microliters) block of the PAG could partially, significantly (P less than 0.05) and reversibly reduce both the APT and cortical-induced depression of the JOR. Lidocaine block of the ventromedial pons reversibly reduced the PAG, APT and cortical-induced inhibition of the JOR (P less than 0.05). Lidocaine block of the lateral RVM had powerfully (P less than 0.01) and reversibly reduced the PAG induced inhibition, but had only a small effect (P less than 0.05) on the APT induced inhibition and no significant effect on the cortical-induced inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855140 TI - Selective degeneration of a putative cholinergic pathway in the chinchilla cochlea following infusion with ethylcholine aziridinium ion. AB - Ethylcholine aziridinium ion (AF64A) diluted in artificial perilymph, or artificial perilymph alone was infused into the cochlea of chinchillas. After a survival time of 7 days, the cochleas were fixed with aldehydes, post-fixed in osmium and embedded in epoxy resin for light and electron microscopy. The ultrastructure of the cochleas infused with artificial perilymph was normal. Infusion of 1 microM AF64A resulted in massive degeneration of the axons of the lateral efferent system, a putative cholinergic pathway that originates in the brainstem and terminates on dendrites of the spiral ganglion innervating cochlear inner hair cells. The axons and terminals of a second putative cholinergic pathway, the medial efferent system which terminates on the outer hair cells, were normal. Infusion of AF64A in a concentration of 10 microM resulted in significant pathology of cochlear and supporting cells as well as the loss of efferent terminals at both inner and outer hair cell regions. The results suggest that AF64A is a selective neurotoxin when used under low-dosage conditions, and that certain pathways may be more susceptible to the effects of AF64A than others. One interpretation of these findings is that lateral efferent axons may have a higher rate of high-affinity choline uptake than terminals of the medial efferent axons. PMID- 1855141 TI - Topographic analysis of field potentials in rat vibrissa/barrel cortex. AB - An 8 x 8 multichannel microelectrode array was used to simultaneously record epicortical field potentials, evoked by displacement of contralateral vibrissae, from a 4 x 4 mm2 area of vibrissa/barrel cortex in 4 rats. The epicortical responses began with early positive (P1) and negative (N1) sharp waves, followed by slower positive (P2) and negative (N2) waves. The potential complex systematically shifted location with vibrissa stimulated, in accordance with the known somatotopic anatomy of vibrissa/barrel cortex. Topographical distributions of potentials at the P1, N1, P2 and N2 peaks were approximately concentric, but had distinct spatial extents, suggesting that they were generated by different but overlapping neuronal subpopulations. We propose that the SEP in the vibrissa/barrel cortex is produced by both sequential and parallel processing of somatosensory information, and that all components of the epicortical SEP are generated only in primary somatosensory cortex of the rat. Applications and weaknesses of topographic analysis methods are discussed. PMID- 1855142 TI - Stimulation-induced peripheral nerve hyperemia: mediation by fibers innervating vasa nervorum? AB - We studied the influence of graded nerve trunk stimulation on endoneurial blood flow (NBF), oxygen tension and pH in the rat sciatic nerve. The purpose of the investigation was to explore changes in the in vivo microenvironment of axons which result from their metabolic activation. Using endoneurial microelectrodes, we made serial measurements before, during and after varying stimulation protocols in curarized animals. NBF was increased by stimulation and the effect was directly related to the frequency, length and intensity of the stimulation train. At an intensity designed to supramaximally recruit myelinated fibers, high frequency (50 and 100 Hz) and prolonged duration (5-15 min) stimulation increased NBF. The effect was partly blocked by infiltration of lidocaine at the stimulating site. High intensity stimulation, designed to also recruit unmyelinated fibers, was particularly effective in enhancing NBF and lowering microvascular resistance. Continuous measurements of endoneurial oxygen and pH tension failed to identify associated declines with stimulation irrespective of the protocol. Both oxygen tension and pH tended to rise with stimulation. These studies confirm the presence of stimulation-induced endoneurial hyperemia but provide no evidence that local hypoxia or acidosis are mechanisms. Stimulation recruitment of vasodilatory axons innervating vasa nervorum may be an alternative explanation. PMID- 1855143 TI - Short-term potentiation of off-responses in turtle horizontal cells. AB - Depolarizing responses to light off were studied in turtle horizontal cells using intracellular recording in the everted eyecup preparation. In many cells the off response showed two components (fast and slow) which could overshoot beyond the steady-state dark level. The peak amplitudes of the fast and slow components increased with increasing duration of the light stimulus. A similar enhancement of the off-responses could also be produced by repetitive stimulation with brief flashes. However, the degree of enhancement produced by repetitive stimulation was greater than could be produced by increasing stimulus duration, and the latency of the onset of depolarization was longer, suggesting that the enhancement produced by repetitive stimulation involves an additional mechanism. Dramatic enhancement of the off-response by stimuli which did not affect the on response during light indicates that the off-response may contain information not present in the on-response. The fast component of the off-response was suppressed to a greater degree than other components by reducing extracellular calcium or in the presence of 500 microM cobalt, suggesting that this component may involve a calcium current. PMID- 1855144 TI - Corticotropin releasing hormone, interleukin-1 alpha, and tumor necrosis factor alpha share characteristics of stress mediators. AB - Interleukin-1 alpha and tumor necrosis factor-alpha induce an increase in pain thresholds in the rat. We now show that also the corticotropin releasing hormone induces an analgesic effect that, similarly to what is observed with the two cytokines, is not reversible by naloxone. Moreover, we also show that after the administration of interleukin-1 alpha, tumor necrosis factor-alpha, and corticotropin releasing hormone, naloxone becomes analgesic itself. A similar observation was also made in the human and the experimental animal after exposure to stressful conditions. The results obtained suggest that the two cytokines share with corticotropin releasing hormone some characteristics of stress mediators. PMID- 1855145 TI - Neuronal survival and neurite growth in cultured cerebral explants: assessment of the effect of cytosine arabinoside using improved stereology. AB - Using improved stereological procedures, based on measurements of the total reference volume, the effect of cytosine arabinoside (AraC) on neurons and non neuronal cells in rat cerebral explants has been reinvestigated. These analyses revealed that, in the AraC-treated explants, neurons support a significantly increased volume of neurites, while the volume of non-neuronal cells in the outgrowth zone is significantly decreased. The total number of neurons is similar in the control and treated explants. Since AraC primarily affects dividing cells, these data suggest that the increased volume of neurites per neuron may be mediated through a curtailment of non-neuronal cell division in the AraC-treated explants. This volumetric approach represents a major improvement on current morphometric approaches for quantifying cultured explants of nervous tissue, and provides important evidence that the previously postulated effects of AraC are real ones. PMID- 1855146 TI - Angiotensin II receptor subtypes in rat brain: dithiothreitol inhibits ligand binding to AII-1 and enhances binding to AII-2. AB - Angiotensin II (AII) receptor subtypes have been proposed on the basis of the selectivity of non-peptide AII antagonists. In the present study, the sulfhydryl reducing agent dithiothreitol (DTT) was found to reduce binding to the AII-1 receptor while enhancing binding at the AII-2 site. The neuroanatomical distribution of these effects were consistent with the distribution of AII-1 and AII-2 receptors, respectively. These data indicate that AII receptor subtypes in the brain can be differentiated by both biochemical and pharmacological means. PMID- 1855147 TI - Nematosomes in external horizontal cells of white perch (Roccus americana) retina: changes during dark and light adaptation. AB - Cytoplasmic inclusions resembling nucleoli and termed nematosomes have been described in several areas of the nervous system but not in the retina. Here we report the presence of these structures in the external horizontal cells of white perch (Roccus americana). Nematosomes were larger and more numerous in dark adapted retinas than in light-adapted ones. An inverse relation of horizontal cell spinules was found in these cells, suggesting that electron-dense material observed in spinules may originate from nematosomes. PMID- 1855148 TI - Compound action potential of nerve recorded by suction electrode: a theoretical and experimental analysis. AB - Suction electrodes are widely used for recording compound action potentials (CAPs) from peripheral nerves or central tracts. Unfortunately, the recordings obtained with suction electrodes often vary over time, making quantitative measurement of CAP amplitude difficult. We developed an equivalent electrical model which predicts that the magnitude of a recorded potential will be linearly related to the resistance of the electrode with a nerve inserted. Mathematical procedures were developed that allow correction of virtually all variability inherent in this type of recording; this variability may arise from resistance drift, variable stimulus artifact, or potentials generated as a result of the current of injury. The validity of the theoretical analysis was confirmed experimentally using rat optic nerves. The magnitude of the CAP and electrode resistance varied spontaneously by as much as 100% over time, due to changes in electrode resistance and size of the stimulus artifact. Because the CAP was linearly related to resistance, it was therefore best quantified by the slope computed from this relationship. The stimulus artifact, unlike the CAP itself, was shown to be independent of recording electrode resistance and therefore only resulted in a variable offset to the area vs resistance linear relationship; the slope of this relationship was unaffected. In the absence of stimulation, a steady negative DC potential was recorded from the optic nerve, which was greatest immediately after dissection, and was also a linear function of electrode resistance. In contrast to CAP amplitude, the latencies of the component peaks within the CAP were not significantly altered by changes in electrode resistance. The experimental results confirmed the validity of the electrical model and demonstrated that suction electrodes can be a very reliable and quantitative recording method if the signals are properly corrected. PMID- 1855149 TI - Treatment with L-dopa in early life restored pituitary-adrenocortical response to emotional stress in adult rats with inherited arterial hypertension. AB - This study investigates the function of the hypothalamic-pituitary-adrenocortical system (HPAS) in adult rats with inherited stress-induced arterial hypertension (ISIAH rats) whose arterial blood pressure was lowered by the dopamine precursor L-DOPA treatment during early development (on days 21-25 of life). The response of the HPAS induced by emotional stress was significantly lower in intact ISIAH rats than in normotensive Wistar animals. Injections of L-DOPA on days 21-23 or 21-25 of postnatal life were followed by a long-lasting complete restoration of the emotional stress response in adult ISIAH rats. The restoring effect of L-DOPA was produced through enhancement of synthesis of the brain noradrenaline and, perhaps, adrenaline. The effect was associated with a normalization of the response of the brain adrenergic system to noradrenaline and did not relate to an increase of the plasma corticosterone level after L-DOPA administration in early ontogeny. PMID- 1855150 TI - Adenosine A1 and non-A1 receptors: intracellular analysis of the actions of adenosine agonists and antagonists in rat hippocampal neurons. AB - Adenosine and its agonists exert a depressant effect on neuronal activity by interacting with the adenosine A1 receptor. There is now also evidence for electrophysiological effects mediated by adenosine receptors other than the A1 type, possibly A2 receptors. A1 and A2 receptor-induced changes in the electrical properties of neuronal membranes were investigated by intracellularly recording from rat hippocampal CA1 neurons and using the adenosine agonists, 5'-N ethylcarboxamidoadenosine (NECA) and R-phenylisopropyladenosine (PIA), and the unselective A1 and A2 receptor antagonist, theophylline and the selective A1 receptor antagonist, 8-cyclopenthyl-1,3-dipropylxanthine (DPCPX). PIA and NECA produced an inhibitory effect which was blocked by DPCPX and thus was mediated by A1 receptors. PIA produced inhibition at lower concentrations (0.1-1 mumol/l) than NECA (0.5-10 mumol/l), whereas at high concentrations (2.5 mumol/l) it exerted a dual effect, i.e. either an inhibitory or an excitatory one. During simultaneous perfusion with the A1 receptor antagonist DPCPX, PIA produced concentration-dependent excitatory effects at concentrations above 1 mumol/l. These excitatory effects were blocked by theophylline. DPCPX produced excitation that was enhanced by NECA. Forskolin caused no change in the membrane properties. It is concluded that (1) NECA and PIA affect the membrane properties not only by an action on the A1 but also on non-A1 receptors, because the excitatory effects of PIA and NECA were insensitive to DPCPX and abolished by theophylline; (2) PIA and NECA are more potent at A1 than at A2 receptors; (3) PIA is more potent than NECA at A1 and A2 receptors; (4) effects mediated by A2 receptors prevail over those mediated by A1 receptors when A2 receptors are activated; and (5) the non A1 receptor-mediated effects are independent of an increased formation of cAMP. PMID- 1855151 TI - Localization of cells containing estrogen receptor-like immunoreactivity in the Brazilian opossum brain. AB - The Brazilian opossum (Monodelphis domestica) is a small, pouchless marsupial whose young are born in an immature, sexually undifferentiated state. Etgen and Fadem, and Handa and coworkers have biochemically detected and characterized estrogen receptors in the forebrain of the Brazilian opossum. In this study, we have examined the distribution of estrogen receptor-like immunoreactive (ER-LI) cells in the brains of gonadectomized male and female Brazilian opossums using Abbott H222 rat monoclonal estrogen receptor antibody (H222 is a gift of Abbott Labs). An indirect immunohistochemical procedure employing the Vectastain Elite system and a nickel-enhanced DAB chromogen was used. A large number of ER-LI cell nuclei were observed in the medial preoptic area, ventral septal nucleus, medial division of the bed nucleus of the stria terminalis, lateral part of the ventromedial hypothalamus, premammillary nucleus, arcuate nucleus, posterior amygdaloid nucleus, and the midbrain central grey. Lower numbers of ER-LI cell nuclei were observed in the intermediate subdivision of the lateral septal nucleus, and in the anterior, medial, and posterior cortical amygdaloid nuclei. The anatomical distribution of ER-LI in the Brazilian opossum brain is similar to that which has been reported for estrogen binding sites following biochemical analysis. Based on these findings, we believe specific regions of the Brazilian opossum brain may serve as substrata for the action of estrogen in the adult. In addition, these results are supportive of the use of this animal model to investigate the organizational effects of estrogen on the developing central nervous system. PMID- 1855153 TI - Gastroenterologic problems. PMID- 1855152 TI - Physicians' guide to driver examination. Fifth edition. PMID- 1855154 TI - General perspectives on the aged gut. AB - It is pertinent to ask what clinical conditions would geriatricians most want gastroenterologists to solve. I believe that the three most important are transfer dysphagia, constipation and diarrhea, and fecal incontinence. With transfer dysphagia, the older patient with central nervous system disease simply has forgotten how to swallow. Is it possible, with sensory retraining techniques, to make an impact upon this disabling problem? Although the healthy elderly appear to perceive constipation more often than they actually suffer from it, evacuation clearly is disturbed in hospitalized and nursing-home residents. Can we develop better prokinetic agents to alleviate this problem? Incontinence, more than any other gastrointestinal condition, leads to the transfer of patients from a protected home environment to a chronic-nursing facility. Can we study the pathophysiology of incontinence intensively, as Dr. Nicholas Read's group in Sheffield, England, has done, and develop approaches to managing this important problem? The presentations in this issue of Clinics in Geriatric Medicine may not provide all of the solutions for clinical problems in the elderly that we seek, but it should be a step in the right direction by making salient new information readily available. PMID- 1855155 TI - Swallowing disorders in the elderly. AB - The classic symptoms of dysphagia, heartburn, and chest pain are the presenting manifestation of oropharyngeal and esophageal disorders in the elderly as well as the young. Several unique conditions, including Zenker's diverticulum and vascular compression of the esophagus, may occur in the elderly. Certain disorders, such as oropharyngeal dysphagia due to neurologic disorder, increase in frequency with age. Treatment approaches are similar in elderly and younger patients, but the potential for adverse drug effects and interaction is greater in the elderly than in the young. PMID- 1855157 TI - Management of upper gastrointestinal bleeding. AB - As the number of elderly Americans dramatically increases over the next three decades, as the amount of NSAID usage in the elderly continues to increase, and as the incidence of ulcer disease continues to increase in the elderly, upper gastrointestinal endoscopy will play an increasingly important role in the management of gastrointestinal hemorrhage. Initial efforts should be directed toward stabilizing the patient and obtaining a history and physical examination. As the number of associated diseases increases in a patient with gastrointestinal hemorrhage, so does risk of mortality. Therefore, it is important to promptly identify the site of bleeding and to stop active or recurrent bleeding by the application of endoscopic therapy. Intravenous sedation should be given cautiously to achieve conscious sedation in a monitored patient. A skilled endoscopist should be available to perform endoscopy and apply the therapeutic modalities of electrocoagulation, photocoagulation, or injection therapy for bleeding or nonbleeding vessels or sclero-therapy for esophageal varices. The key to success is to identify the site of bleeding and then act on the finding as clinically indicated. By doing so, it appears that the cost of hospitalization and the mortality in the elderly patient are reduced. PMID- 1855156 TI - Acid peptic disease in the elderly. AB - Research in epidemiology and related fields highlights three factors contributing to a high prevalence of complications of ulcer disease in the elderly, namely anti-inflammatory drugs (aspirin and NSAIDs), type B gastritis due to H. pylori infection, and smoking; these factors also increase the prevalence of both GU and DU. The major dangers with ulcer disease arise from continued exposure to the causative risk factors, absent or insidious symptoms, difficulties in diagnosis, late presentations, high rates of complications (often the presenting features), high preoperative and perioperative mortality, and serious postoperative morbidity (especially in smokers). Empiric therapy and the use of diagnoses such as nonulcer dyspepsia invite additional hazards. Once diagnosed and adequately treated, ulcers in the elderly behave similarly to those in younger subjects matched for risk factors, and they respond well to treatment. In high-risk elderly patients without previous or active ulcer disease, misoprostol may be used to prevent gastric ulcers; other benefits of the drug await clarification. In those with previous or active ulcer disease, H2-antagonists given long-term in higher doses appear preferable. Side effects of antiulcer drugs are rarely serious and are easily managed by dose reductions or changes in products. The major benefits to the management of ulcers in the elderly come from increased vigilance on the part of physicians. PMID- 1855158 TI - Irritable bowel syndrome in the elderly. AB - Although few studies to elucidate the epidemiology and pathophysiology of the irritable bowel syndrome (IBS) in people over the age of 65, it is our thesis that the problem is underrecognized in older people. The available data suggest that 10% to 20% of elderly people in the general population have IBS. The causes remain unknown, but age-related changes are unlikely to alter the underlying pathogenesis. Treatment is still largely empiric, symptomatic, and often unsatisfactory; the problems of treating IBS in the elderly are compounded by the frequency of untoward side effects of drugs in this age group. PMID- 1855159 TI - Inflammatory bowel disease in older people. PMID- 1855160 TI - Lower intestinal bleeding in the elderly. AB - Lower intestinal bleeding in the elderly is a common problem with numerous and varied causes. Its diagnosis and treatment require a careful, systematic approach by physicians with special expertise. Under the proper circumstances, elderly patients with lower intestinal bleeding do well, even when surgery is required. An individual's age, by itself, should not preclude aggressive medical care. PMID- 1855162 TI - Cancer of the colon and rectum. AB - Colorectal cancer remains a significant medical illness and a leading cause of death in the geriatric population. Improvements in management include postoperative surgical adjuvant therapy for colonic cancer and postoperative chemotherapy and radiation for rectal cancer. Some advancement in the diagnostic and screening aspects has occurred. Management decisions in the older patients should follow the same principles as those in the younger age group, although preoperative medical evaluation is especially necessary to evaluate risk and optimize surgical, chemotherapeutic, and palliative outcomes. The best treatment for colon cancer, as for any malignancy, remains prevention. Therefore, additional efforts should focus on developing new and improved screening modalities (especially in the high-risk groups) to identify and remove premalignant lesions as well as to detect early-stage, and therefore potentially curable, large-bowel cancer. PMID- 1855161 TI - Gastrointestinal and other vulnerabilities for geriatric globetrotters. AB - An awareness of the journey's destination and the consequential events along the way will better enhance our diagnoses and in turn sustain our elder "homo turisticus," no longer an endangered species but worthy of our continued compassionate care while enjoying their longevity. All potential treacheries must be assessed by each elderly traveler. It may be the first of many trips or the last opportunity to view and relate to the sequoia's longevity, hike the Scottish highlands, view the game of the Serengeti, explore the Nordic fjords, indulge in the Patagonian scenes of the Iguazu falls, seek the habitats of the Galapagos tortoise, partake of the photograph opportunities of Papua-New Guinea, or finalize that "last" business contract in the Orient. With consideration of these many vulnerabilities and potential hazards, why then undertake the journey? Perhaps our geriatric globetrotters give credence to the age-old saying (of unknown origin) "Running water never freezes." PMID- 1855163 TI - Biliary tract disease in the aged. AB - Gallstone disease occurs in 20% to 30% of the elderly, is usually silent, and is rarely fatal. Silent GSD requires no treatment. Symptomatic GSD can be treated surgically, nonsurgically, or, if there are minimal symptoms, expectantly. The decision is based largely on physician experience and informed patient preference. Nonsurgical treatment is evolving and has particular appeal for the elderly but does have restricting eligibility requirements and limited efficacy. For acute cholecystitis, early surgery is advisable, except for high-risk patients, in whom conservative treatment or cholecystostomy may be preferable. For choledocholithiasis with persistent obstruction or cholangitis and for severe biliary pancreatitis, ERCP with sphincterotomy and stone removal is usually advisable. Benign biliary strictures are infrequent, usually iatrogenic, and a diagnostic consideration whenever biliary obstruction develops within a year after cholecystectomy. Treatment is usually surgical and not always successful. Biliary strictures in patients with ulcerative colitis suggest PSC. Malignant biliary obstruction is common in the elderly and with a few exceptions is rarely curable. Palliation is often achieved by endoscopic stenting. PMID- 1855164 TI - Liver diseases in the elderly. AB - The preceding discussions outline the various forms of cirrhosis that may be encountered in the elderly population. Cirrhosis is not uncommon in older patients. Although it has been stated that most cirrhosis in the elderly is due to alcohol, these assumptions are perhaps overestimations. In the authors' experience, many older patients are inappropriately labeled with alcoholic liver disease--presumed guilty until proven otherwise--and have subsequently been shown to have nonalcoholic liver disease. Careful investigation is required. Hepatotoxic drug exposure (e.g., to alpha methyldopa, nitrofurantoin, or isoniazid) should be ruled out, and hepatitis B and hepatitis C serology obtained. Primary biliary cirrhosis may occur in both sexes, and thus antimitochondrial antibody should be assayed. Severe heart disease may result in cardiac cirrhosis in the elderly, with ascites and hepatomegaly. Alpha 1 antitrypsin deficiency, primary sclerosing cholangitis, idiopathic hemochromatosis, and chronic autoimmune hepatitis may result in advanced cirrhosis in the elderly; appropriate serum studies should be obtained. If questions remain and if therapy may be changed, liver biopsy can be performed. A recent study suggested, however, that the risk of hemorrhage from liver biopsy in the elderly may be increased, especially if malignancy is present. The era of treatment for liver diseases has arrived. Colchicine, methotrexate, ursodeoxycholic acid, and others have shown promise in the treatment of PBC, primary sclerosing cholangitis, and alcoholic liver disease. Corticosteroids may be lifesaving in autoimmune liver disease. Phlebotomy remains the treatment of choice for hemochromatosis in any age group. Interferons and other antiviral agents are being used in chronic type B and type C hepatitis. Treatment of the complications of cirrhosis in the elderly may be safely accomplished. Advanced age is not a contraindication to variceal sclerotherapy. Vasopressin, however, may be contraindicated in the elderly patient if there is an underlying history of atherosclerotic coronary or peripheral vascular disease. Large-volume paracentesis and peritoneal venous shunting can afford symptomatic relief of ascites, even in the geriatric population. Finally, as noted previously, advanced age is no longer to be considered an absolute contraindication for liver transplantation. The evaluation of liver disease in the elderly may be diagnostically challenging, and its treatment rewarding. PMID- 1855165 TI - A philosophic approach to aging. AB - Who are the old? Is age a category, like sex? Does just getting to a certain age justify certain rewards and certain limits? Is there a role for old physicians working in a hospital? What should age be a criterion for? There are no firm answers, but there should be more discussion. PMID- 1855166 TI - Ovarian cancer screening. PMID- 1855167 TI - Irrationality in the management of breast cancer. I. The staging system. AB - The historic development of breast cancer staging began early in the 20th century with the simple concept of early localized disease, spread to regional nodes, and the presence of distant metastases. This last group often was divided into patients with advanced but perhaps still curable locoregional disease and incurable patients with distant metastases. As increasing numbers of prognostic factors were recognized, efforts were made to incorporate them into the staging systems to combine patients with similar prognosis into the same stages. These attempts resulted in the development of four classifications, namely, the Columbia, Manchester, International, and American tumor-node-metastasis (TNM) staging systems. Although many benefits of staging were reported, the most important was that of permitting valid comparisons between different treatments and different institutions. Many success-limiting factors were noticed during the developmental years, and even though the TNM system has been accepted, numerous speakers and authors present their staged data in a confusing and ambiguous manner. Recommendations are made that would permit clarification of presentations to general medical audiences along with recognizable statistical validity. PMID- 1855168 TI - Mitoxantrone and high-dose etoposide for patients with relapsed or refractory acute leukemia. AB - Among 35 patients with relapsed or refractory acute myelogenous leukemia (AML) who received salvage chemotherapy, 28 were treated with mitoxantrone (7.5 mg/m2/d intravenously [IV] over 1 hour for 5 days) and etoposide (VP-16) (2 g/m2 over 4 days either as a daily infusion or as two daily doses). Seven patients received mitoxantrone (6 mg/m2/d for 5 days) and VP-16 (1500 mg/m2 over 3 days). The median duration of the initial complete remission (CR) was 6 months and 83% of the patients had initial CR that lasted 12 months or less. Forty-six percent of the patients were undergoing a second or subsequent salvage attempt. Eight patients (23%) achieved CR; seven of these CR were obtained after one course of therapy. Twelve patients (33%) died and 15 patients (42%) had disease that was resistant to treatment. Patients undergoing a first salvage attempt had a higher incidence rate of CR than those undergoing a second or subsequent salvage attempt (37% versus 6%; P = 0.03). CR rates were also higher in patients with a favorable (translocation 8;21 or 15;17) or diploid karyotype compared with other patients (32% versus 8%; P = 0.10). The median survival time was 2 months for all patients and 8 months for patients achieving CR. Mucositis occurred in 74% of the patients and was severe in 32%. Diarrhea and rash occurred in less than 33% of the patients. Fever was noticed in all but 1 of the patients and documented infections occurred in 65% of the patients. Six patients had pancytopenia or thrombocytopenia that lasted more than 42 days from the initiation of treatment. Although mitoxantrone and high-dose VP-16 is an effective antileukemic regimen, it is associated with a high incidence of mucositis. Strategies that are used to limit mucosal damage may improve the tolerance of this combination. PMID- 1855169 TI - A combination trial of human lymphoblastoid interferon and bestrabucil (KM2210) for adult T-cell leukemia-lymphoma. AB - Both human lymphoblastoid interferon (HLBI) and bestrabucil, the conjugate of chlorambucil and beta-estradiol, have antitumor activity against adult T-cell leukemia-lymphoma (ATLL). Because an in vitro study showed that these two agents combined had a synergistic antiproliferative effect on MOLT-4 and WI-38VA13 cell lines, the authors evaluated the clinical efficacy of this combination in a pilot study with a poor-risk group of ATLL patients. The patients were treated daily with 6 x 10(6) IU of HLBI subcutaneously and 100 mg of bestrabucil orally. In patients with lymphoma-type ATLL or hypercalcemia, prednisolone also was given daily. Of 12 patients suitable for evaluation, nine had partial responses, one had a minor response, and two had no response. All five patients with skin infiltration and both patients with hypercalcemia responded. A history of prior chemotherapy did not affect the response rate. The time to clinical response was 3 to 16 days (median, 11 days) after initiation of treatment. The response duration was 4 to 108+ weeks (median, 9 weeks), but all patients except one relapsed, even during continuing treatment. No serious side effects were observed. Although the response rate with this combination treatment was high, the response duration was short, and other treatments would have to be added to achieve control of this aggressive disease. PMID- 1855170 TI - Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma. AB - Between January 1988 and June 1990, seven previously untreated patients with histologically confirmed and clinically staged IIIa invasive thymoma (IT) were enrolled in a prospective, single treatment arm study of neoadjuvant chemotherapy (NC) followed by surgery and postoperative radiation therapy (4600 to 6000 cGy). The NC included three cycles of cisplatin (75 mg/m2 on day 1), epirubicin (100 mg/m2 on day 1), and etoposide (120 mg/m2 on days 1, 3, and 5), every 3 weeks. All patients showed a partial response (greater than 50%) and underwent complete (n = 4) or incomplete (gross [n = 1] or microscopic [n = 2] residual tumor) surgical resection. Histologic examination was negative for two completely resected patients. Projected 2-year survival was 80%; all patients but one currently are alive and disease-free. This approach appeared to be feasible and may be a new therapeutic choice in the management of IT, but its use on a regular basis should be reserved until a larger number of patients and longer follow-up are available. PMID- 1855171 TI - Adjuvant intraperitoneal chromic phosphate therapy for women with apparent early ovarian carcinoma who have not undergone comprehensive surgical staging. AB - Forty-nine women with apparent Stage I and II ovarian carcinoma received intraperitoneal phosphate 32 as the only adjuvant therapy after primary surgery. In addition to bilateral salpingo-oophorectomy, 40 (82%) had analysis of peritoneal cytology, and 35 (71%) underwent omentectomy. Random peritoneal biopsies and retroperitoneal lymph node sampling were not done in any of these patients. The overall and disease-free survival rates were 86% and 75%, respectively, with no significant differences by stage, histologic grade, histologic type, or low-risk versus high-risk subsets recognized in patients who received comprehensive surgical staging. Seven (58%) of 12 patients had lymph node metastasis as the first site of recurrence, including two of three with late recurrences. Significant morbidity related to intraperitoneal chromic phosphate (32P) occurred in one (2%) woman. These results emphasize the need for comprehensive surgical staging of women with apparent early ovarian carcinoma to aid in the selection of appropriate initial adjuvant therapy. PMID- 1855172 TI - Increased survival, limb preservation, and prognostic factors for osteosarcoma. AB - Preoperative intraarterial (IA) cisplatin (CDP) was administered to 92 patients with nonmetastatic osteosarcoma. The ages of the patients ranged from 4 to 28 years. Sixty-four patients (70%) received 2 or 3 preoperative courses and 28 (30%) received 4 or more. Sixty-two specimens were available for pathologic examination to assess the degree of tumor necrosis. More than 90% tumor destruction was observed in 16 of 42 patients (38%) who received 1 to 3 preoperative courses as opposed to 17 of 20 (85%) who received 4 or more courses. Patients who received 4 or more courses had a 2-fold probability of achieving more than 90% tumor necrosis, and 68% underwent conservative surgery. Of those who received 3 or less courses, 23% underwent conservative surgery. Postoperatively, patients were treated with intravenous (IV) CDP alternating with doxorubicin (ADR) (Adriamycin, Adria Laboratories, Columbus, OH). Pulmonary metastases developed in 36 patients, bone metastases in 2, and local recurrence in 6. Two patients died of cardiac failure without evidence of disease. Thus, 46 patients (50%) were continuously free of disease 18 to 78 months after diagnosis. Univariate and multivariate analyses showed that male sex, low grade preoperative chemotherapy-induced necrosis, and nonosteoblastic histologic condition were prognostic factors predictive of recurrence, while male sex and large tumor size were prognostic factors predictive of death. These results are comparable with those reported by other centers and are superior to our previous experiences that yielded survival rates of 5% to 10%. A substantial number of patients also had the opportunity to achieve tumor removal with conservative surgery. PMID- 1855173 TI - Limb salvage surgery for bone and soft tissue sarcoma. A phase II pathologic study of preoperative intraarterial cisplatin. AB - Preoperative therapy has been tested as part of limb salvage therapy for localized bone and soft tissue sarcoma of the extremities. The activity of cisplatin (CDDP) by intraarterial (IA) infusion was evaluated in 40 cases of which 36 were evaluable for response. All patients had high-grade sarcomas. All but 3 patients received 3 or 4 courses (24 patients received 4 courses) of CDDP at a dosage of 120 to 150 mg/m2 given over 6 hours every 2 weeks by IA infusion. Patients younger than 18 years of age received the higher dose of CDDP. Treatment was well tolerated with combination antiemetics. One patient experienced severe hearing loss with the first cycle of the higher CDDP dose. Pathologic evaluation of resected osteosarcoma showed a favorable response (90% or greater necrosis) in 8 of 20 evaluable cases and in 3 of 4 patients with malignant fibrous histiocytoma (MFH) of bone (without osteoid). In soft tissue sarcomas, minimal (50% to 89%) necrosis was seen in two of nine cases and none had 90% or greater necrosis. Patients received postoperative chemotherapy based on pathologic response, but the value of this postoperative adjuvant therapy requires further follow-up and is uncertain in this small study. IA CDDP can often cause significant tumor necrosis in patients with bone sarcomas, whereas soft tissue sarcomas are less sensitive to this therapy. PMID- 1855174 TI - Dual modulation of 5-fluorouracil using leucovorin and hydroxyurea. A phase I trial. AB - Oral hydroxyurea (HU) was added to a regimen of 5-fluorouracil (5-FU) plus leucovorin (LCV) administered as a continuous 24-hour infusion for 14 days. A previous report of the 5-FU plus LCV infusion established optimal dosages of 200 mg/m2/d and 5 mg/m2/d, respectively, for each agent. Oral HU was added to the regimen in total dosages of 0.5 g/d, 1.0 g/d, 1.5 g/d, or 2.0 g/d. Twenty-two patients received a total of 45 courses of treatment. Stomatitis was the dose limiting side effect; it occurred in 3 of 14 courses with HU at 0.5 g/d (21%) and 9 of 17 courses with HU at 1.0 g/d (53%). Dosage escalation to 1.5 g/d or 2.0 g/d was possible in only 3 of 22 patients (17%). The median time to stomatitis was 10 days (range, 7 to 12 days). One response was observed in this heavily pretreated population. Phase II trials of HU plus LCV dual modulation of infusional 5-FU should use initial HU dosages of 0.5 g/d for the 14-day regimen described, with dose escalation as tolerated. Variable oral absorption presumably accounts for the small group of patients who can tolerate the higher doses of HU. PMID- 1855175 TI - Lymphomatous presentation of childhood acute lymphoblastic leukemia. A subgroup at high risk of early treatment failure. AB - Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, E-rosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/microliters, male predominance, and older age. This type of presentation of ALL is referred to as the "lymphoma syndrome" (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E-rosette-positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease-free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL. PMID- 1855176 TI - Surgically induced cytokinetic responses in experimental rat mammary tumor models. AB - The effect of surgical removal of "primary" tumors on the cytokinetics of local tumor remnants, secondary implants, and metastases was investigated in three different rat tumor models in the Wag/Rij rat: a slow-growing (MCR83) and a fast growing (EMR86) hormone-dependent mammary tumor and a rapidly, but autonomously growing carcinoma (MCR86). The latter two tumors had metastatic potential. Cell kinetic studies were done using in vivo labeling with 5'-bromodeoxyuridine (BrdUrd). Thirty-three hours after removal of a subcutaneous MCR83 flank tumor, secondary implants showed a significant (P less than 0.05) but transient increase in the BrdUrd labeling index (LI). A more rapid and prolonged increase, lasting for at least 7 days, was observed in EMR86 lymph node and lung metastases. In both models, no effect was observed after sham surgery (consisting of opening and closing of the skin under anesthesia). Removal of MCR86 tumors (growing in the hind leg muscle) also resulted in a rapid, transient LI increase in metastases. Continuous BrdUrd labeling experiments in this tumor model did not favor the hypothesis that the LI increase predominantly resulted from an increase in the growth fraction. Moreover, in this model, the effect was related to operation trauma. A similar increase in LI, although smaller than after tumor removal, was seen after major surgical trauma in MCR83 flank tumors. These results indicate that in the rat, tumor removal and/or major surgical trauma may modulate the cytokinetics of distant metastases significantly. A study of the systemic, possibly endocrine, factors involved in the growth-stimulating effect of surgical trauma in these rat tumor models may help to assess the clinical relevance of these findings for patients with breast cancer. PMID- 1855177 TI - Lymphocyte abnormalities predicting a poor prognosis in Hodgkin's disease. A long term follow-up. AB - Two hundred sixty-two adult patients with Hodgkin's disease (HD) were studied. Incorporation of carbon-14-thymidine was measured in unstimulated monocyte depleted lymphocyte cultures, and in cultures activated by concanavalin A (Con-A) before institution of therapy in all patients. Total blood lymphocytes and T-cell subsets were enumerated in the last 108 patients. Patients had significantly decreased total (CD3+, CD4+, CD8+) and relative (CD3+, CD4+) T-cell counts compared with healthy controls. Stage IV patients tended to have lower total lymphocyte and subset counts than remaining patients. However, significantly reduced total lymphocyte and CD8+ counts were only observed in comparison to patients in clinical stage II. Thirty-three percent of patients had an increased spontaneous and a decreased Con-A-induced blood lymphocyte DNA synthesis. Functional lymphocyte abnormalities were related to advanced clinical stage, high age, mixed cellularity, and lymphocyte depletion histopathology and presence of B symptoms. The 10-year survival of patients in this group was 36%, compared with 62% for the remainder. In a multivariate analysis of the whole series lymphocyte DNA synthesis was besides age the strongest predictor of prognosis. In univariate analyses of the second patient series total lymphocyte, T-cell and subset counts were related to prognosis. These relatively simple lymphocyte functional tests may help to identify young HD patients for whom intensive cytoreductive therapy with or without autologous stem cell support may be the best therapeutic option. PMID- 1855178 TI - Statin immunolocalization in human brain tumors. Detection of noncycling cells using a novel marker of cell quiescence. AB - Surgical specimens of 35 human brain tumors were examined with a novel monoclonal antibody, S-44, immunoreactive to statin, a nuclear protein specifically expressed in quiescent (noncycling) G0-phase cells. Benign tumors typically were statin positive with labeling indices (LI) between 22% and 96%: acoustic schwannomas (n = 3, mean = 29.9 +/- 19.4%); meningiomas (n = 4, mean = 59.0 +/- 15.1%); pituitary adenomas (n = 3, mean = 79.9 +/- 28.2%), and an epidermoid cyst (41.0%). By contrast, the statin LI of 18 of 24 (75%) malignant brain tumors was less than or equal to 2%: medulloblastomas (n = 7, mean = 0.3 +/- 0.2%); anaplastic astrocytomas (n = 3, mean = 1.6 +/- 2.7%); glioblastomas (n = 10, mean = 10.3 +/- 14.4%); metastatic carcinomas (n = 3, mean = 3.0 +/- 4.6); and a germinoma (0.2%). The vascular endothelium among diverse tumors typically was statin positive. All 21 tumors with a statin LI less than 10% were malignant, and all nine tumors with a statin LI greater than 40% were benign. The statin LI of benign tumors (n = 11, mean = 55.1 +/- 26.7%) was significantly higher than that of the malignant tumors (n = 24, mean = 5.2 +/- 10.5%, P less than 0.001). The absence of statin expression is a new way to determine the malignancy of human brain tumors. The statin LI may be useful to guide the prognosis and treatment of individual patients. The mechanisms that control statin expression are important in therapy seeking to shift the proliferating, cycling cells to the quiescent, G0 compartment. PMID- 1855179 TI - Primary intracerebral osteosarcoma. AB - A 64-year-old man was admitted because of a rapidly progressive left side hemiparesis. A computed tomography scan showed a right side intrathalamic mass, partially calcified. Surgical specimen proved to be an osteosarcoma. The patient died 3 days later from an acute myocardial infarct. Autopsy failed to discover any other significant lesion. A review of the literature disclosed that this case might be the second published primary intracerebral osteosarcoma and the first with immunocytochemical analysis. PMID- 1855180 TI - Basic fibroblast growth factor and somatomedin C in human medulloepithelioma. AB - Two published cases of medulloepithelioma, a rare malignant pediatric brain tumor composed of a mixture of primitive neuroepithelium and its differentiated neuronal and glial descendants, were examined by immunohistochemical staining for the presence of growth factors. From a panel of antibodies, those identifying basic fibroblast growth factor and insulin-like growth factor I, formerly known as somatomedin C, were strongly immunoreactive within the neuroepithelial cell population of the tumors. Immunoblots of purified recombinant basic fibroblast growth factor and insulin-like growth factor I showed antibody specificity without cross-reactivity. In controls, immunostaining of tissue sections was abolished by preabsorption of primary antibodies with the appropriate growth factor polypeptide antigen. Preabsorption with inappropriate growth factor did not reduce the intensity or alter the distribution of staining. The congruent histologic patterns of immunoreactivities suggest that more than one type of growth factor may be produced by the neuroepithelial component of medulloepithelioma. These growth factors may stimulate proliferation and differentiation of tumor cells by autocrine molecular mechanisms. PMID- 1855181 TI - Immunohistochemical evaluation of uveal melanocytic tumors. Expression of HMB-45, S-100 protein, and neuron-specific enolase. AB - The authors compared the immunohistochemical reactivity of 13 uveal nevi and 20 uveal melanomas for HMB-45, S-100 protein, and neuron-specific enolase (NSE) in formalin-fixed, paraffin-embedded sections. All 33 of the lesions were positive for HMB-45. The false-negative rates for S-100 protein and NSE were 21% and 18%, respectively. If only strongly positive reactions were considered, more than 50% of the tumors would be interpreted as negative for S-100 protein and NSE. Nevi stained with less intensity than melanomas using all three antibodies. The expression of HMB-45 appeared to be greater in active nevi than in inactive nevi. There was a weak association between S-100 protein reactivity and the ability of the uveal melanomas to metastasize (P = 0.1); however, the standard deviation of nucleolar area was a much better predictor (P = 0.02). These results indicate that pathologists will find HMB-45 to be a useful tool in differentiating uveal melanoma from nonmelanocytic tumors. PMID- 1855182 TI - Nuclear DNA content, tumor cell aggregation, and metastatic events in patients with poorly differentiated adenocarcinoma of the stomach. AB - Data on 100 patients who had undergone resection for poorly differentiated adenocarcinoma of the stomach with serosal invasion were examined to assess the prognostic significance of the DNA distribution pattern in relation to the histologic tumor cell aggregation pattern. DNA distribution patterns were classified into low and high ploidies and tumor cell aggregation patterns were classified into free-cell, small nest, and large nest types. The rates of high ploidy in the free-cell, small nest, and large nest types were 23.1%, 48.0%, and 66.7%, respectively, with a significant increase according to the degree of aggregation. The high ploidy group and large nest type had a higher incidence of lymphogenous and hematogenous metastasis than the low ploidy group and free-cell type, respectively. DNA ploidy had no prognostic value for the free-cell type of tumor, but differences in prognosis and the incidence of metastasis between the DNA ploidies were evident in the nest-forming type. Aneuploid tumors consisting of a poorly differentiated adenocarcinoma were those with nest formation, from the standpoint of histologic structure and metastatic behavior. The DNA analysis of poorly differentiated adenocarcinomas was of prognostic value, especially in the nest-forming type. PMID- 1855183 TI - A clinicopathologic study of lymphoid neoplasias associated with human immunodeficiency virus infection in Italy. AB - The clinicopathologic features of 45 human immunodeficiency virus (HIV)-infected patients (mainly intravenous drug users [IVDU]) with lymphoid neoplasias seen from September 1984 through July 1990 at an Italian cancer center are reviewed. Thirty-five had systemic non-Hodgkin's lymphoma (NHL), and ten had Hodgkin's disease (HD). Histologically, 27 NHL cases were intermediate grade (five cases) or high grade (22 cases, 14 of the small noncleaved cell type), according to the Working Formulation. Eight NHL cases, including four anaplastic large cell (ALC) BerH2 (CD30)-positive lymphomas, were in the miscellaneous group. Immunohistologic and/or gene rearrangement analysis showed the B-cell origin of 20 of the 24 NHL cases studied. At presentation, 71% of NHL patients had advanced stages (Stage III or IV), and 85% had extranodal disease (predominantly gastrointestinal tract and marrow). Of the 23 patients evaluable for treatment, only seven had a complete clinical response after lymphoma therapy; the median survival of 34 evaluable patients was 22 months after the diagnosis of NHL. Fifteen patients died; most deaths were attributable to progressive lymphoma and opportunistic infections. As with NHL, advanced disease, extranodal involvement, aggressive histologic findings, and poor response to therapy were also observed in patients with HD. This study shows that lymphoid neoplasias occurring in Italian IVDU with HIV infection and those previously reported in North American homosexual men with HIV infection share similar clinicopathologic features. However, some features such as the absence of history of Kaposi's sarcoma at diagnosis, the lack of detection of primary brain and rectal NHL, and the occurrence of B-cell ALC BerH2 (CD30)-positive NHL were observed uniquely in this series of patients. PMID- 1855184 TI - Pleomorphic xanthoastrocytoma. Ultrastructural, immunohistochemical, and DNA cytofluorometric study of a case. AB - A case of right frontal pleomorphic xanthoastrocytoma that occurred in a 7-year old boy is reported clinicopathologically. The patient underwent surgery on September 29, 1988. Histologic diagnosis of pleomorphic xanthoastrocytoma was made because, in addition to the unique pleomorphic histologic features, positive glial fibrillary acidic protein in immunohistochemical staining and characteristic ultrastructural features, i.e., cytoplasmic intermediate fibrils and lipid vacuoles, basal lamina, and abundant reticulin networks were demonstrated. The DNA cytofluorometric analysis of the nuclei of the tumor cells disclosed the main mode to be diploid with polyploid classes (4, 8, 16, and 32C) without any aneuploidy. Despite the presence of many pleomorphic nuclei, DNA histogram of the tumor disclosed very few DNA synthetic cells indicating a biologically inactive nature of the tumor. The patient is still alive and totally asymptomatic 20 months postoperatively. PMID- 1855185 TI - The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas. AB - From 1962 to 1987, 126 patients underwent trans-sphenoidal surgery for primary treatment of pituitary adenomas unassociated with clinical or biochemical evidence of hormonal overproduction. There were 73 male and 53 female patients (mean age, 50 +/- 12 years). Before surgery, 56% of the patients (70 of 124) had headaches, 74% (94 of 126) had deterioration of vision, and 12% (15 of 126) had ophthalmoplegia. Endocrine evaluation revealed the presence of hypogonadism in 75% (87 of 115), adrenal insufficiency in 36% (46 of 126), and hypothyroidism in 18% (21 of 122). Plasma prolactin was increased in 65% (56 of 86) with a mean level of 39 +/- 14 micrograms/l (normal, 3 to 20 micrograms/l). Radiologic enlargement of the sella turcica was documented in all cases: 67% (84 of 126) had enclosed and 33% (42 of 126) had invasive adenomas. After surgery, vision was normalized or improved in 75% (71 of 94) of the patients. Thyroid, adrenal, and gonadal functions were improved in 14% (three of 22), 41% (19 of 46), 11% (ten of 87), were unchanged in 82% (100 of 122), 77% (97 of 126), 89% (102 of 115), and worsened in 15% (19 of 22), 8% (ten of 126), 3% (102 of 115), respectively. Permanent diabetes insipidus occurred in 5% (seven of 126). Two patients died during the immediate postoperative period. The recurrence rate in patients with a mean follow-up of 6.4 +/- 4.2 years was 21% (15 of 71). These data indicate that trans-sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism. PMID- 1855187 TI - Pattern of cell kinetics in colorectal mucosa of patients with different types of adenomatous polyps of the large bowel. AB - It is generally accepted that adenomatous polyps represent the natural precursor of many colorectal malignancies. The sequence, however, which leads from a normally appearing mucosa to cancer is complex and involves many steps, including a hyperproliferative mucosa with an upward expansion of the replicative compartment. The current study evaluates cell replication in normal colorectal mucosa of patients with adenomatous polyps of various types and relates the observed findings to the main clinical and morphologic features of adenomas. Forty-four patients with polyps and 27 controls entered the study. Samples of colorectal mucosa were taken at endoscopy and cell replication was evaluated with a standard autoradiographic procedure. Cell replication was expressed as labeling index (LI), in the whole crypt and in each of the five longitudinal compartments in which the crypts were divided. Total LI and LI per crypt compartment were significantly higher (P less than 0.02 and P less than 0.01, respectively) than in controls. There was no appreciable difference of LI values between patients with single or multiple, tubular or tubulovillous, small or large adenomas, but in all of these subgroups LI was significantly higher than in controls. In conclusion, in normally appearing colorectal mucosa of patients with adenomatous polyps there was a significant increase of cell replication and a marked upward expansion of the proliferative zone; these changes were more evident in the left colon and in the rectum. Finally, cell replication did not seem to be related to the number of polyps, to the most common histotypes, or to the pattern of recurrence. PMID- 1855186 TI - The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen. AB - Four hundred fifteen patients with metastatic breast cancer with known hormone receptor status received primary treatment with tamoxifen. Measured values for the estrogen receptor (ER, i.e., with estrogen binding) followed a continuous distribution (range, 3 to 1000 fmol/mg of protein). These values correlated positively with age. The response to treatment with tamoxifen correlated with the ER level, with response rates of approximately 80% when the ER level was greater than 30.1 fmol/mg of protein. Two hundred eighteen (218 of 415, 52%) patients had progesterone receptor (PR) values greater than 10 fmol/mg. The PR positivity correlated with the ER level. Patients with PR levels greater than 10 fmol/mg of protein (124 of 226, 55%) had a significantly higher response rate than those with values less than 10 fmol/mg of protein (45 of 189, 24%). However, in a multivariate analysis including both receptor levels, age, site, and number of metastases, only the ER level was significant in predicting the response to treatment with tamoxifen. A quantitative estimation of the ER level thus is the best predictor of response to hormonal treatment with tamoxifen for advanced breast cancer. PMID- 1855188 TI - DNA ploidy and cell kinetic measurements as predictors of recurrence and survival in stages B2 and C colorectal adenocarcinoma. AB - DNA content and cell proliferation were measured by flow cytometry on paraffin embedded Stage B2 or C colorectal adenocarcinomas from 694 patients enrolled in adjuvant trials conducted by the North Central Cancer Treatment Group. Patients with diploid tumors had a higher survival rate than those with nondiploid tumors (P less than 0.001). The proliferation index (the sum of the percent of cells in S-phase plus those in G2M phase) was also a strong prognostic factor (P less than 0.001). The ploidy and proliferation data were combined, and the patients in the favorable group (diploid and low proliferative index) had a 5-year survival of 74% compared with 54% for the unfavorable group (high proliferative index or nondiploid, P less than 0.001). This grouping was prognostic for survival in B2 (P less than 0.001), C (P = 0.013), colon (P less than 0.001), and rectal (P = 0.026) patient subsets. This study indicates that cell kinetic parameters are important and independent prognostic factors for Stages B2 and C colorectal cancer. PMID- 1855189 TI - Esophageal obstruction 14 years after treatment for Hodgkin's disease. AB - The incidence of late radiation injury of the esophagus is not precisely determined but, overall, the occurrence of clinically apparent damage is infrequent. The authors report a complete esophageal obstruction in a 21-year-old man, 14 years after chemo-radiation therapy for Hodgkin's lymphoma. Although endoscopy failed to demonstrate a gross morphologic abnormality, an esophagogram detected abnormal peristalsis and stricture, and esophageal manometry coupled with dynamic isotopic study clearly demonstrated a multilevel secondary neuronal damage. Data in the literature suggest that alteration in motility is by far the most frequent radiologic manifestation. Further prospective studies will probably clarify the actual incidence of late esophageal damage after chemo-radiation therapy. PMID- 1855190 TI - Risk factors for bilateral testicular germ cell tumors. Does heredity play a role? AB - Twenty-three bilateral testicular germ cell tumors (four synchronous and 19 sequential tumors) were investigated for potential risk factors. The incidence of maldescensus testis was not found to be higher than in patients with unilateral disease. The histologic findings of the first tumor did not have any effect on the incidence of the second tumor. In 21 patients (four synchronous and 17 sequential tumors), histocompatibility antigens (HLA) were determined; HLA-B14 was increased significantly in the sequential tumor group. Tendencies toward an increase of HLA-DR5 and HLA-DR7 also were found. The HLA-DR1, HLA-DR3, and HLA DR4 showed a tendency toward a decreased frequency. Therefore genetic factors might be important in the development of sequential bilateral testicular cancers. PMID- 1855191 TI - Alpha-interferon (IFN) in the treatment of metastatic carcinoid tumors. PMID- 1855192 TI - Effect of 'Pan Masala' on the germ cells of male mice. AB - Cytogenetic analyses of meiotic metaphase I germ cells and abnormalities of head morphology of caudal sperms were conducted in male mice following oral feeding of Pan Masala. The substance was ground to a fine powder, dispersed in polysorbate solution and administered via gavage to the animals at 84, 420 and 840 mg/kg body weight at the rate of 10 ml/kg body weight. Polysorbate and cyclophosphamide served as the vehicle control and positive control respectively. The two higher doses, 420 and 840 mg, gave a significant increase in the frequency of X-Y univalents and breaks over those of the vehicle control. Frequency of sperm head abnormalities were significantly high for all the doses tested. The results indicate that Pan Masala is a potent clastogen, reaches the testes and affects the germinal cells. PMID- 1855193 TI - Postnatal vaginal nodules induced by prenatal diethylstilbestrol treatment correlate with later development of ovary-independent vaginal and uterine changes in mice. AB - Pregnant ICR/JCL mice were given 4 daily subcutaneous injections of 0.2-2000 micrograms diethylstilbestrol (DES) starting on day 15 of gestation. Offspring of mothers given DES were killed at 1-10 days of age and examined for nodules of enlarged polygonal cells under the epithelium of the Mullerian (upper) vagina. Some offspring were ovariectomised at 30 days and killed at 120 days. The nodules which appeared in the prenatally DES-exposed mice (2-2000 micrograms/day) at 3-7 days were not connected with the epithelium of the sinus vagina and reacted positively to an antibody to epidermal growth factor. Nodule formation may prove to be prodromic of later ovary-independent vaginal changes in the DES-exposed mice. Epithelial stratification (2-2000 micrograms/day) and downgrowths and/or pegs (20-2000 micrograms/day) occurred in vaginae of ovariectomized mice exposed prenatally to DES; however, adenosis-like lesions occurred only in the offspring of mothers given the highest prenatal injections of 2000 micrograms DES. Wolffian remnants and hypospadias (2-2000 micrograms/day) were also encountered in the DES exposed mice. Ovary-independent stratification of the uterine epithelium (20-2000 micrograms/day) and disorganization of the circular musculature (2-2000 micrograms/day) were also observed in the DES-exposed mice. None of these changes was found in ovariectomised 0.2 micrograms DES-exposed and control mice. PMID- 1855194 TI - Tumorigenicity of the tobacco-specific carcinogen 4-(methyl-nitrosamino)-1-(3 pyridyl)-1-butanone in infant mice. AB - The tobacco-specific nitrosamine, 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a potent carcinogen in adult rodents and variably effective transplacentally, depending on species. In pursuit of the thesis that human infants may be especially vulnerable targets for tumor initiation by tobacco smoke constituents, we tested the efficacy of NNK as a tumor initiator in infant mice. Cr:NIH(S) (NIH Swiss outbred) mice were given 50 mg/kg NNK i.p. on postnatal days 1, 4, 7, 10 and 14, with saline to controls. At an average age of 13-15 months, 57% of the NNK-exposed male offspring had hepatocellular tumors, with a multiplicity of 1.15 +/- 1.4, including 4 with carcinoma. Liver tumors including 2 carcinomas were found in 8 (14%) of the NNK-exposed female offspring. There were no hepatocellular neoplasms in any control. A significant increase in primary lung tumors also occurred in the NNK-treated males, with an incidence of 30/55 (57%) and a multiplicity of 0.7 +/- 0.2, vs. 7/33 (21%), multiplicity 0.3 +/- 0.6, in controls (P less than 0.025). An apparent increase in the incidence of lung tumors in NNK-treated females, 21/57 (37%) vs. 7/32 (22%) in controls, approached significance (P less than 0.1). Thus NNK was a moderately potent neonatal carcinogen for liver and lung in infant Swiss mice and more efficacious in this regard than when received transplacentally by mice of the same strain. PMID- 1855195 TI - Distinct patterns of phorbol ester-induced downregulation of protein kinase C activity in adriamycin-selected multidrug resistant and parental murine fibrosarcoma cells. AB - Specific activators of protein kinase C (PKC), including the phorbol-ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), can reduce the chemosensitivities of a variety of mammalian tumor cell lines and their cytotoxic drug-selected multidrug resistant (MDR) variants to MDR-linked drugs, thus implicating PKC in the MDR phenotype. Previously, we reported that the adriamycin selected MDR murine fibrosarcoma cell line UV-2237M-ADRR has approximately twice as much PKC activity as the parental UV-2237M line. In this report, we show that the level of [3H]phorbol-12,13-dibutyrate specific binding activity was elevated 3.5-fold in the MDR cells, thus establishing that phorbol-ester responsive PKC is overexpressed in the MDR line. Phorbol esters mediate downregulation of PKC by stimulating proteolysis of the enzyme, without altering the rate of PKC synthesis. We report that the kinetics of TPA-induced downregulation of PKC activity differ markedly in parental and MDR UV-2237M cells, providing evidence that the overexpression of phorbol-ester responsive PKC in adriamycin-selected MDR UV-2237M-ADRR cells results, at least in part, from a reduced rate of PKC degradation in the cells. PMID- 1855196 TI - 32P-postlabeling analysis of DNA adducts in rat livers after treatment with genotoxic and non-genotoxic 4-aminoazobenzene derivatives. AB - Formation of hepatic DNA adducts was studied in rats following intraperitoneal administration of a hepatocarcinogen, 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and a non-hepatocarcinogen, 2-methoxy-4-aminoazobenzene (2-MeO-AAB). The 32P-post labeling assay revealed 3-MeO-AAB to give more than 20-fold higher amounts of DNA adducts than did 2-MeO-AAB. Furthermore, five adducts, one of which accounted for over 70% of the total modified bases, were found in DNA from 3-MeO-AAB-treated rats, whereas only one adduct was apparent in 2-MeO-AAB-treated DNA. Our data thus suggested that the difference in hepatocarcinogenic activity between 3-MeO AAB and 2-MeO-AAB might be, at least in part, dependent on quantitative and qualitative differences in their azo dye-DNA adduct formation in the rat liver. PMID- 1855197 TI - Mouse liver free amino acids during the development of Ehrlich ascites tumour. AB - Sequential amino acid concentrations were determined in the liver of mice infested with a highly malignant strain of Ehrlich ascites tumour cells. The liver concentrations of a certain group of amino acids showed changes consistent with those previously reported for plasma, ascitic liquid and tumour cells during tumour growth. Shortly after tumour transplantation a significant decrease of the essential amino acids methionine, threonine, valine, isoleucine + phenylalanine, leucine, lysine and histidine, was detected. Some non-essential amino acids, mainly the gluconeogenic substrates alanine and serine, showed a strong reduction in hepatic concentrations during the first days; these amino acids remained significantly lower than controls until animal death. Interestingly, hepatic glutamine increased at days 1 and 2 after inoculation, and proline showed a sustained increase from the seventh day onwards, reaching a value double the control at the end of animal life. PMID- 1855198 TI - Lack of modification by naturally occurring antioxidants of 3,2'-dimethyl-4 aminobiphenyl-initiated rat prostate carcinogenesis. AB - The modifying effects of 6 naturally occurring antioxidants on 3,2'-dimethyl-4 aminobiphenyl (DMAB)-initiated rat prostate carcinogenesis were investigated in male F344 rats. Animals were pretreated with DMAB in a 20-week initiation protocol and then administered basal diet containing 0.8% catechol, 0.8% resorcinol, 0.8% hydroquinone, 2 ppm selenium, 2% gamma-orysanol or 1% alpha tocopherol for 40 weeks. The experiment was terminated at week 60 for histopathological assessment of lesion development. Atypical hyperplasias and carcinomas of the prostate were observed in the ventral lobe in all groups treated with DMAB. However, the incidences of these lesions were not significantly different between carcinogen control and antioxidant-treated groups. There were also no significant increases or decreases in the incidences of tumors in any other organs. PMID- 1855199 TI - Glycoprotein patterns in normal and malignant cervical tissue. AB - Glycoproteins from normal and malignant human cervix were studied using an organ culture system and compared by gel electrophoresis and autoradiography. Five glycoproteins of 178 kDa, 95 kDa, 93 kDa, 82 kDa and 38 kDa and 1 glycolipid (46 kDa) were detected more frequently in squamous carcinomas. Certain glycoproteins were shown to be oncofoetal and some had affinity for Concanavalin A (Con A). The 82 kDa glycoprotein was present in 16/17 squamous carcinomas but in only 1/13 normal cervices. This band represented a glycoprotein containing glucosamine, mannose, small quantities of methionine and no fucose. These preliminary results suggest that these glycoproteins and in particular the 82-kDa glycoprotein are worthy of further investigation and characterisation. PMID- 1855200 TI - Cellular energetics measured by phosphorous nuclear magnetic resonance spectroscopy are not correlated with chronic nutrient deficiency in multicellular tumor spheroids. AB - We have measured the 31P nuclear magnetic resonance spectra of EMT6/Ro multicellular tumor spheroids over a wide range of sizes under constant nutrient conditions which matched those used for culturing the spheroids. The amount of nucleotide triphosphate per cell decreased with spheroid growth, roughly in proportion to the decrease in cell volume. There was no correlation between the intracellular pH, the nucleotide triphosphate:Pi ratio, or the phosphocreatine:Pi ratio and either the spheroid cellularity, the mean cell volume, the S-phase fraction, the clonogenic capacity, or the amount of central necrosis. The phosphoryethanolamine:phosphorylcholine ratio also increased with increasing spheroid size. There was a negative correlation between the phosphoryethanolamine:phosphorylcholine ratio and the S-phase cell fraction or the mean cell volume; this ratio was positively correlated with the extent of central necrosis. The membrane degradation components glycerophosphorylcholine and glycerophosphorylethanolamine showed no significant changes with increasing spheroid size. These results imply that spheroid necrotic areas induced by chronic nutrient deficiencies are "invisible" to 31P nuclear magnetic resonance and that the development of cellular quiescence in spheroids is not caused by a decrease in the steady-state level of high-energy phosphates or a reduced intracellular pH. Together, these data support a model in which cells maintain normal steady-state levels of high energy phosphates until they are very close to necrotic cell death. This implies that the deterioration of 31P nuclear magnetic resonance spectra of tumors with increasing size is not caused by chronic nutrient deficiencies resulting from cells outgrowing the capillary supply, but rather is more related to transient nutrient deprivation phenomena. PMID- 1855201 TI - Lung cancer-associated protein: development and characterization of a new assay that detects a circulating lung cancer marker. AB - A panel of murine monoclonal antibodies was generated against a high-molecular weight glycoprotein produced by human lung cancer cells. This lung cancer associated protein (LCAP) has been shown to circulate in the plasma of patients with lung cancer. Various combinations of MAbs were used in solid-phase enzyme linked sandwich immunoassays to optimize the detection of LCAP in the plasma of these patients. One of these monoclonal antibodies, designated DF-L1, used both in the solid phase as well as the tracer, was selected to evaluate circulating levels of LCAP in normal subjects and in patients with lung cancer. In 341 normal subjects, the mean LCAP level was 7 units/ml, with 47 (13.8%) and 18 (5.3%) subjects having levels greater than or equal to 15 units/ml and 23 units/ml, respectively. In contrast, 27 of 35 (77.1%) patients with lung cancer had LCAP levels greater than or equal to 23 units/ml. A total of 16 of 19 (84.2%) patients with adenocarcinoma, four of seven (57.1%) patients with squamous cell carcinoma, and four of six (66.7%) patients with small cell carcinoma had levels greater than or equal to 23 units/ml. Moreover, in a small group of patients, serial LCAP levels correlated with clinical course during therapy. The LCAP assay is technically reproducible and unaffected by interfering substances in the blood or by variations in the handling of samples. These results indicate that LCAP is a new and potentially useful marker for the evaluation of patients with lung cancer. PMID- 1855202 TI - Comparison of estrogen receptors in hormone-dependent and hormone-independent Grunder strain mouse mammary tumors. AB - Hormone-dependent (HD) Grunder strain mouse mammary carcinomas contain a 65-kDa estrogen receptor (ER) with minor amounts of 50- and 35-kDa components which apparently still contain the intact hormone-binding (COOH-terminal) domain. When the HD tumors lose their hormonal dependence during serial transplantation, the hormone-independent (HI) transplants show an increase in 50- and 35-kDa components relative to 65-kDa ER. In HI transplants of three of five tumor lines studied (TSl 85, 86, and 106), the 65-kDa receptor was entirely replaced by 50- and 35-kDa receptors, whereas in the two other lines (TSl 101 and 104) there usually were about equal amounts of 65- and 50-kDa ERs. No difference was found between ERs of HD and HI tumors in affinity for estradiol, steroid specificity, or immunoreactivity for the monoclonal antibody JS34/32. Estrogen stimulation of HI tumors did not increase the concentration of progesterone receptor in the tumor tissue, indicating that ER in these tumors was not functional in enhancing progesterone receptor. Incubation of 65-kDa ER with HI tumor cytosol or combined homogenization of HD and HI tumor tissue did not cause degradation of 65-kDa ER. alpha-Chymotrypsin-like protease activity generally was lower in HI than in HD tumor cytosols, indicating that the lower molecular size of ER in HI tumors cannot be attributed to the increased level of this protease activity. PMID- 1855203 TI - Interaction between ionizing radiation and supercoiled DNA within human tumor cells. AB - We have analyzed DNA supercoiling within histone-free nuclei (nucleoids) using four human squamous cell carcinoma cell lines that express varying degrees of radiosensitivity. The entire DNA, arranged as negative supercoiled loops attached to the nuclear matrix, was extracted from single cells, stained with ethidium bromide, and passed through a flow cytometer recording both light scatter and red (DNA) fluorescence. Supercoiled loops of DNA from all cells were unwound with a low concentration of ethidium bromide, as seen by increased light scatter. Nucleoids from radiosensitive but not radioresistant cells resisted the transition from zero to positive supercoiling at higher concentrations of ethidium bromide. The profile of red DNA fluorescence from ethidium bromide stained nucleoids showed that the radiosensitive cells expressed a greater variation in the total amount of ethidium bromide bound. After 12 Gy of gamma radiation, radiosensitive cell lines produced nucleoids that contained a greater proportion of relaxed supercoiled DNA, making them larger than those from radioresistant cell lines. We suggest these observations are secondary effects resulting from an altered affinity between supercoiled looped DNA and the nuclear matrix. Combined with radiation damage, these structural alterations may lead to a more complex type of damage to repair within the radiosensitive cell lines. PMID- 1855204 TI - Studies on the interaction between interleukin 6 and human malignant nonhematopoietic cell lines. AB - We have previously reported on stimulation of clonal growth of cell lines from human solid tumors by recombinant human interleukin 3, recombinant human granulocyte-macrophage colony-stimulating factor, and recombinant human granulocyte colony-stimulating factor (W. E. Berdel et al., Blood, 73: 80-83, 1989; Exp. Hematol., 16: 510, 1988). Within an extensive screening program of hematopoietic growth factor activity on malignant cells, the effects of recombinant human interleukin 6 (rhIL-6) were tested on the growth (tritiated thymidine uptake and human tumor cloning assay) of 26 different human cell lines derived from a wide range of solid tumors (head and neck, 4; lung, 1; pancreatic, 1; gastric, 1; colorectal, 3; renal, 3; bladder, 1; prostate, 1; breast, 2; ovary, 2; choriocarcinoma, 1; sarcoma, 2; glioblastoma, 2; neuroblastoma, 2). rhIL-6 (dose range up to 10(4) IU/ml) caused no reproducible enhancement or inhibition of tritiated thymidine uptake by tumor cell lines from nonhematopoietic origin. Furthermore, 19 of the tumor cell lines were clonogenic in a capillary modification of the human tumor cloning assay. No reproducible stimulation of clonal growth by rhIL-6 was observed in any of the cells tested. Particularly, there was no sensitivity of those cell lines for rhIL-6, which were previously shown to be sensitive for recombinant human interleukin 3 and recombinant human granulocyte-macrophage colony-stimulating factor in this assay. On the other hand, there were no significant growth-inhibitory effects of rhIL-6 on the cell lines tested in this study. Further experiments showed no influence of neutralizing monoclonal anti-hIL-6 antibody on the growth of 3 kidney carcinoma cell lines, making autocrine growth-modulating loops for IL-6 in these lines unlikely. In conclusion, no major interactions between hIL-6 and the growth of the human malignant cell lines from nonhematopoietic origin tested were detected in this study. PMID- 1855205 TI - A potent specific pure antiestrogen with clinical potential. AB - Previous studies from this laboratory have described a series of 7 alpha alkylamide analogues of estradiol with pure antiestrogenic activity, exemplified by ICI 164,384. A new compound, 7 alpha-[9-(4,4,5,5,5 pentafluoropentylsulfinyl)nonyl]estra-1,3,5(10 )- triene-3,17 beta-diol (ICI 182,780) has now been identified which has significantly increased antiestrogenic potency and retains pure estrogen antagonist activity. The antiuterotrophic potency of ICI 182,780 in the immature rat was more than 10-fold greater than that of ICI 164,384 (50% effective doses of 0.06 and 0.9 mg/kg, respectively). This order of magnitude increase of in vivo potency was also reflected, in part, by intrinsic activity at the estrogen receptor. The relative binding affinities of ICI 182,780 and ICI 164,384 were 0.89 and 0.19, respectively, compared with that of estradiol (1.0). Similarly, the in vitro growth-inhibitory potency of ICI 182,780 exceeded that of ICI 164,384 in MCF-7 human breast cancer cells, where 50% inhibitory concentrations of 0.29 and 1.3 nM, respectively, were recorded. ICI 182,780 was a more effective inhibitor of MCF-7 growth than 4' hydroxytamoxifen, producing an 80% reduction of cell number under conditions where 4'-hydroxytamoxifen achieved a maximum of 50% inhibition. This increased efficacy was reflected by a greater reduction of the proportion of cells engaged in DNA synthesis in ICI 182,780-treated cell cultures compared with tamoxifen treated cells. Sustained antiestrogenic effects, following a single parenteral dose of ICI 182,780 in oil suspension, were apparent in both rats and pigtail monkeys. In vivo, antitumor activity of ICI 182,780 was demonstrated with xenografts of MCF-7 and Br10 human breast cancers in nude mice. A single injection of ICI 182,780 provided antitumor efficacy equivalent to that of daily tamoxifen treatment for at least 4 weeks. The properties of ICI 182,780 identify this pure antiestrogen as a prime candidate with which to evaluate the potential therapeutic benefits of complete estrogen withdrawal in endocrine-responsive human breast cancer. PMID- 1855206 TI - Elevated 8-hydroxydeoxyguanosine levels in DNA of diethylstilbestrol-treated Syrian hamsters: covalent DNA damage by free radicals generated by redox cycling of diethylstilbestrol. AB - The generation of free radicals by microsome-mediated redox cycling between catechol estrogens or diethylstilbestrol and their corresponding quinones has previously been demonstrated in vitro. However, the reaction of free radicals with DNA has not yet been detected in animals treated with estrogen and is the subject of this investigation. The reaction of guanine bases of DNA with hydroxyl radicals to form 8-hydroxydeoxyguanosine has been used as a monitor of free radical generation in kidney and liver of Syrian hamsters, a species prone to estrogen-induced carcinogenesis. Prior to in vivo measurements, the in vitro hydroxylation of guanine bases of DNA under conditions of redox cycling of estrogen was investigated. In incubations of DNA or deoxyguanosine with hamster kidney microsomes, NADPH, and diethylstilbestrol 4',4"-quinone, the hydroxylation of guanine bases of free deoxyguanosine or of DNA was 50 to 100% higher than in controls. When incubations were carried out in the presence of iron(III) chloride, the hydroxylation of guanine bases was 2.5- or 10-fold higher than control values. There was a 65% increase from control values in levels of 8 hydroxydeoxyguanosine in liver DNA of hamsters treated with 20 mg/kg/day diethylstilbestrol for 3 days and 100 mg/kg on the 4th day. In hamsters treated chronically with diethylstilbestrol implants for 15 days, 8-hydroxydeoxyguanosine levels more than doubled from control values in kidney but not liver DNA. Treatment of hamsters with estradiol for various time periods did not induce any changes in levels of hydroxylated guanine in either kidney or liver. It was concluded that in vitro and in vivo redox cycling of diethylstilbestrol hydroxylated guanine bases in DNA. PMID- 1855207 TI - Therapeutic analysis of melphalan-resistant human rhabdomyosarcoma xenograft TE 671 MR. AB - Investigations with the melphalan-resistant human rhabdomyosarcoma xenograft TE 671 MR were carried out to identify patterns of cross-resistance and collateral sensitivity and to define the mechanism(s) mediating melphalan resistance. TE-671 MR was cross-resistant to thio-TEPA, mitomycin, vincristine, and cisplatin, and partially resistant to chlorambucil and cyclophosphamide. TE-671 MR and the parent line TE-671 were both resistant to 1,3-bis(2-chloroethyl)-nitrosourea and expressed similar levels of O6-alkylguanine-DNA alkyltransferase. TE-671 MR retained full sensitivity to actinomycin D and demonstrated enhanced sensitivity to VP-16 compared to TE-671. Treatment of TE-671 MR with melphalan plus VP-16 resulted in greater than additive growth delays. The frequency of hypoxic regions was similar in TE-671 MR and TE-671, respectively. Measurement of tumor-to-plasma levels at 180 min following i.p. administration of melphalan at 0.5 of the 10% lethal dosage showed mean tumor-to-plasma ratios of 3.81 in TE-671 MR and 7.38 in TE-671, respectively. The lower drug levels in TE-671 MR may be contributing to the resistance to melphalan and thus indicate the need for further studies to define the reasons for these differences in tumor drug level. PMID- 1855208 TI - Species differences in metabolic activation and inactivation of 1-nitropyrene in the liver. AB - To extrapolate from animal studies to humans the risk of 1-nitropyrene (1-NP), we determined the differences between human and experimental animals in oxidative activation of 1-NP to 1-NP oxides and inactivation of 1-NP oxides by epoxide hydration and glutathione conjugation in hepatic subcellular fractions from 6 species including humans. Species differences were found in both activation of 1 NP and inactivation of 1-NP oxides. 1-Nitro-4,5-dihydro-4,5-epoxypyrene-producing activity was highest in guinea pig and dog, followed by hamster, rat, human, and mouse. 1-Nitro-9,10-dihydro-9,10-epoxypyrene-producing activity was highest in hamster, followed in order by guinea pig, rat, dog, mouse, and human. The ratio of 1-nitro-4,5-dihydro-4,5-epoxypyrene to 1-nitro-9,10-dihydro-9,10-epoxypyrene also varied with the animal species. Hydration of 1-nitro-4,5-dihydro-4,5 epoxypyrene was highest in human, followed by dog, guinea pig, hamster, rat, and mouse. 1-nitro-9,10-dihydro-9,10-epoxypyrene was a poor substrate for epoxide hydrolase in all species. Glutathione conjugation of 1-NP oxides in rodents was higher than that in human and dog. In humans, hepatic microsomes produced the lowest level of 1-NP oxides but hydrolyzed them most efficiently, and glutathione conjugation activity of the cytosol was as low as in dogs, and there was a wide degree of interindividual variations in these activities. No single species studied was a good model for humans, and the balance of activation/inactivation tends toward detoxification in these adult animals. PMID- 1855209 TI - Elevated formation of nitrate and N-nitrosodimethylamine in woodchucks (Marmota monax) associated with chronic woodchuck hepatitis virus infection. AB - Nitrate balance and N-nitrosodimethylamine (NDMA) excretion were studied in woodchucks chronically infected with woodchuck hepatitis virus (WHV). Twenty-four h urinary recovery of a bolus dose of [15N]nitrate was 54 +/- 12% in woodchucks. WHV-infected animals formed 3-fold more nitrate endogenously than did control animals (P less than 0.01). Treatment of WHV-infected animals with Escherichia coli lipopolysaccharide increased nitrate excretion 15-fold, while uninfected animals increased nitrate excretion 4-fold. The endogenous formation of NDMA was higher in WHV-infected woodchucks than in uninfected controls. After administration of L-[15N2]arginine, [15N]nitrate, and [15N]NDMA were detected in urine indicating that arginine is a precursor of biosynthesized nitrate and the hepatocarcinogen NDMA. NDMA probably results from the formation of nitrosating agents during the oxidation of arginine to oxides of nitrogen and citrulline. Woodchucks chronically infected with WHV develop hepatocellular carcinomas with high frequency. Our observations suggest an additional mechanism that may be involved in the pathogenesis of hepatocellular carcinoma associated with chronic WHV infection. PMID- 1855210 TI - DNA sequence specificity of doxorubicin-induced mutational damage in uvrB- Escherichia coli. AB - In the absence of excision repair, doxorubicin caused a striking (41-fold) increase in the frequency of large deletion mutations extending from the lac operator (lacO) into the lac repressor gene (lacI) of Escherichia coli. In contrast, there was only a 2-fold increase in the frequency of small deletions despite a 3-fold increase in overall mutation frequency. The 5'-endpoints of doxorubicin-induced lacO and lacI/lacO deletions occurred at the DNA sequence 5' pyTAA or 5'-AATpy (where py is pyrmidine) (16%), at runs of purines or pyrimidines (41%) and adjacent to 5'-dGdC or 5'-dCdG doublets (34%). Ninety % (27 of 30) of the doxorubicin-induced deletions involving the region of the lacO palindrome had 3'-endpoints within the palindrome sequence as compared with 40% (4 of 10) spontaneous deletions in an untreated set. Doxorubicin-induced single base substitutions were highly focused at one site (4 of 6) in the i-d region of lacI, in contrast to the spontaneous distribution of point mutations, where 16 mutants were recovered at 12 different sites. An increased frequency (3-fold) of highly focused base substitutions was also observed at 2 sites in the lac operator region (at lacO +6, which is a transition "hotspot" in the spontaneous spectra of both wild type and uvrB- organisms and at the adjacent +5 site). Notably, the frequency of 1- and 2-base frameshifts did not increase in the doxorubicin-induced spectrum, relative to the spontaneous mutation spectrum. These in vivo observations in E. coli suggest that in the absence of excision repair, doxorubicin causes highly focused deletions and base substitutions. These mutations occur adjacent to DNA sequences identified in previous in vitro studies as preferential sites of doxorubicin binding. PMID- 1855211 TI - Ionic and ligand-specific effects on the DNA binding of progesterone receptor bound to the synthetic progestin R5020 and the antiprogestin RU486. AB - Antiprogestin and other antihormones are valuable therapeutic agents in hormone responsive cancers. A fundamental mechanism in the action of antiprogestin is its binding to PR,3 an intracellular protein that mediates the action of progesterone by direct interaction at the regulatory sites of responsive genes. To elucidate the mechanism of action of PR bound to agonistic and antagonistic ligands, we determined the binding affinity of rabbit uterine PR bound to R5020 and RU486, respectively, with different DNA sequences. We used 2 recombinant plasmid DNAs, pDHf14 and pDHf2, with 60- and 23-base pair inserts of potential Z-DNA-forming (dA-dC)n.(dG-dT)n sequences, respectively, parental plasmid pDPL6 with no insert, calf thymus DNA, and several synthetic polynucleotides in this study. The concentration of DNA required to elute 50% of the receptor bound to DNA-cellulose (EC50) was used as a measure of the relative binding affinity of the receptor for DNA. EC50 values of plasmids pDHf14 and pDHf2 were 1.2 +/- 0.5 (SD) and 2.5 +/- 0.6 micrograms/ml, respectively, for PR bound to R5020. In contrast, EC50 for control plasmid was 350 micrograms/ml. PR.R5020 had lower affinity for calf thymus DNA and polynucleotides compared with pDHf2 and pDHf14. Receptors complexed with the antiprogestin RU486 had lower affinity for the plasmids; EC50 values were 2.4 +/- 0.4 and 10 +/- 1 microgram/ml, respectively, for pDHf14 and pDHf2. This ligand-specific difference in DNA binding was amplified by the presence of 5 mM Mg2+ or Ca2+. The relative binding affinity of PR.R5020 to pDHf14 was 6- and 7-fold higher than that of PR.RU486, in the presence of 5 mM Mg2+ and Ca2+, respectively. These results show that PR.RU486 has lower binding affinity for specific DNA sequences than PR.R5020, but the binding affinity of both receptors is in a range that cannot preclude competitive interactions at the DNA recognition site. The effects of Mg2+ and Ca2+ on PR binding to DNA further suggest that these cations could affect PR recognition of DNA in a ligand specific manner. PMID- 1855212 TI - Metabolism, sister chromatid exchanges, and DNA single-strand breaks induced by 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone and their modulation by vitamin A in vitro. AB - The nicotine-derived N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) is abundant in smokeless tobacco and tobacco smoke and is hepatocarcinogenic in F344 rats. We have investigated how vitamin A modulates sister chromatid exchanges and DNA single-strand breaks induced by NNK. In V79 cells, vitamin A at concentrations ranging from 34.9 to 139.6 microM inhibited sister chromatid exchange frequencies induced by 20 mM NNK activated by primary rat hepatocytes. Sister chromatid exchanges were inhibited by 24, 44, and 55% when cells were cotreated with 34.9, 69.8, and 139.6 microM vitamin A, respectively. DNA single-strand breaks induced by NNK in rat hepatocytes were also inhibited by vitamin A. After 9 h of elution, DNA single-strand breaks induced by 1, 5, and 10 mM NNK were inhibited by 13, 5, and 3.5% in the presence of 69.8 microM vitamin A, respectively. This protective effect by vitamin A was associated with a reduction of alpha-carbon hydroxylation, an activation pathway of NNK. This pathway was inhibited by 50% when cells were cotreated with 3.49 microM vitamin A. The reduction in the hepatic microsomal aminopyrine N demethylase, aniline hydroxylase, and N,N-dimethyl aniline N-demethylase in the presence of vitamin A (0.035 to 0.35 microM) suggests that vitamin A could reduce NNK genotoxicity by inhibiting the enzymes involved in the activation process. PMID- 1855213 TI - Novel Chinese hamster ultraviolet-sensitive mutants for excision repair form complementation groups 9 and 10. AB - In this paper we demonstrate that the mutants CHO7PV and CHO4PV isolated by us from the CHO-K1 prol- cell line represent two new complementation groups of UV sensitive excision repair-defective rodent mutants. We have classified the mutant CHO7PV as representative of Group 9 and CHO4PV as representative of Group 10. Cellular and biochemical characterization of these mutants indicates that they are moderately sensitive to a broad spectrum of mutagens (UV and mono- and bifunctional alkylating agents), partially unable to perform UV-induced DNA repair synthesis, and partially defective in the incision step of the DNA excision repair pathway and in the removal of the two main lesions caused by UV [cyclobutane pyrimidine dimers and (6-4) photo-products]. In terms of UV survival and incision, CHO4PV is apparently more defective than CHO7PV (40% and 50% of wild-type survival, respectively, and 55% and 75% of wild-type incision), whereas when repair DNA synthesis and lesion removal are compared, CHO7PV seems to be more severely affected (30% of wild-type unscheduled DNA synthesis in CHO7PV and 60% in CHO4PV). This suggests a subtlety in the relation between removal of these specific lesions and overall repair capacity and survival. PMID- 1855214 TI - Tumor necrosis factor/cachectin decreases catalase activity of rat liver. AB - Tumor bearing hosts and animals treated with endotoxin commonly show a decrease in the catalase activity of the liver and kidney. Since tumor necrosis factor (TNF)/cachectin may play a significant role in these conditions, we investigated its effects on the catalatic and peroxidatic activity of catalase in the liver and kidney of the rat. The activities of glucose-6-phosphate dehydrogenase and lactate dehydrogenase were measured simultaneously to monitor the pentose phosphate and glycolytic pathways, respectively. Injection i.p. of 100 micrograms/kg/day human recombinant TNF-alpha for 5 days resulted in a significant (P less than 0.01) decrease in the catalatic activity of the liver when compared to rats fed ad libitum. The decrease in four experiments ranged from 21 to 56%. A significant decrease (18%; P = 0.01) in liver catalatic and peroxidatic activity was also observed in another experiment using pair fed rats as controls. The peroxidatic activity of catalase with ethanol as hydrogen donor closely paralleled the catalatic activity. TNF treatment had no detectable effect on the catalatic or peroxidatic activity of catalase in the kidney. The activity of glucose-6-phosphate dehydrogenase increased (31-80%) significantly (P less than or equal to 0.02) in the liver and, to a lesser extent, in the kidney (5 27%, P = 0.05). Lactate dehydrogenase activity decreased (14-19%) significantly (P less than or equal to 0.05) in the liver and kidney but mainly in rats treated with TNF and additionally fasted for 24 h. Electron microscopic examination of liver sections showed that the hepatocytes of TNF-treated rats were undamaged but contained fewer and smaller peroxisomes than those of the control rats. PMID- 1855215 TI - Inhibition of c-myc expression by phosphorothioate antisense oligonucleotide identifies a critical role for c-myc in the growth of human breast cancer. AB - In search of critical genes in the mechanism of estrogen action in human breast cancer, we previously showed that estrogen stimulates transcription of the c-myc gene in estrogen-dependent (MCF-7) cells. We have now examined the role of c-myc in estrogen-stimulated growth of MCF-7 cells through the use of a synthetic antisense c-myc phosphorothioate oligonucleotide to specifically inhibit expression of the c-myc protein. Estrogen induces a 5-fold increase in c-myc protein expression within 90 min in steroid-deprived cells, as detected by Western blot. Prior exposure of MCF-7 cells to 10 microM c-myc antisense oligonucleotide results in up to 95% inhibition of the c-myc protein expression induced by estrogen. Antisense-myc oligonucleotide inhibits estrogen-stimulated cell growth by up to 75% over 9 days and also exerts a cytostatic effect on the growth of estrogen-independent MDA-MB-231 cells which show relatively high, constitutive expression of c-myc. Sense-myc and antisense-pS2 oligonucleotides have no effect on c-myc protein level or growth in either cell line. These results demonstrate both the specific and durable effects of antisense phosphorothioate oligonucleotides. Furthermore, these results indicate a critical role for c-myc in the growth of breast cancer cells and support the hypothesis that loss of estrogen regulation of this gene may be an important factor in the progression of breast cancer. PMID- 1855216 TI - Therapy of human cervical carcinoma with monoclonal antibody-Pseudomonas exotoxin conjugates. AB - Pseudomonas exotoxin A (PE) linked to the F(ab')2 fragment of 1H10, a murine monoclonal antibody recognizing a carbohydrate epitope of a glycoconjugate expressed on the surface of human cervical carcinoma tumor cells, was evaluated for in vitro and in vivo activity. PE can kill cells by ADP-ribosylating elongation factor 2 thus inhibiting protein synthesis. Disulfide- as well as thioether-linked immunotoxins (1H10-PE) killed cervical carcinoma cells in vitro and were 20-160 times more inhibitory to target than to control cells. Cell killing was antibody mediated as demonstrated by the reduction of 1H10-PE growth inhibition to target CaSki cells by free 1H10 F(ab')2. In addition, a control antibody immunotoxin was nontoxic to CaSki cells. Thioether-linked 1H10-PE administered either i.v. or i.p. suppressed the growth of established solid s.c. cervical carcinoma tumors xenografted in nude mice for over 30 days. Treatment with antibody alone or a control immunotoxin had no significant effect on tumor growth. Administration of immunotoxin i.p. was associated with less toxicity than administration i.v., but i.v. injections were more effective at suppressing the growth of established solid tumors. PMID- 1855217 TI - Development of two new monoclonal antibodies reactive to a surface antigen present on human ovarian epithelial cancer cells. AB - Monoclonal antibodies which bind selectively to cancer cells are currently used for tumor localization and for targeting cytotoxic reagents. The success of these approaches depends on the specificity of the antibody and its reactivity to a majority of the tumor samples. Frequently, monoclonal antibodies are generated by immunizing mice with antigenic preparations from a single tumor cell line. Antibodies generated under these conditions often react to a narrow range of tumors. In the present study, mice were immunized with multiple ovarian cancer cell lines in a sequential manner to amplify the immune response against common antigenic determinants expressed in these cell lines. Spleen cells from the immunized mice were then fused with NS-1 myeloma cells to establish hybridomas. Two cell lines were selected on the basis of their selective reactivity to ovarian cancer cells after extensive screening. Monoclonal antibodies OVX1 and OVX2 bound to all 5 ovarian carcinoma cell lines tested and did not bind to normal fibroblast cells. These antibodies recognized a unique antigenic determinant present in ovarian and breast cancer cells. Cross-blocking studies showed that the binding of OVX1 and OVX2 is not displaceable by 10 other previously described anti-ovarian antibodies including OC125. In immunocytochemical studies, OVX1 reacted to a majority of ovarian cancer tissues (17 of 20) and did not bind to normal ovarian tissues. Preliminary results indicate that OVX1 and OVX2 antibodies are directed to a high molecular weight antigen. These antibodies could be used in the preparation of cytotoxic conjugates. PMID- 1855218 TI - Antitumor effect of Nocardia rubra cell wall skeleton on syngeneically transplanted P388 tumors. AB - The antitumor activity of the immunomodulator, Nocardia rubra cell wall skeleton (N-CWS), was investigated using syngeneically transplanted P388 leukemia cells in a solid form. The s.c. growth of P388 tumors in DBA/2 mice was significantly suppressed by systemically administered N-CWS, and the effect was dose dependent. The antitumor effect of N-CWS was partially but significantly abrogated in splenectomized mice but not in T-cell or natural killer cell-deficient mice. Although spleen cells from mice treated with 1600 micrograms N-CWS contained no cytolytic activity, they exerted a significant cytostatic effect on P388 cell growth both in vitro and in vivo. Splenic cytostatic activity did not reside in T or natural killer cells, but in plastic adherent cell population, macrophages. The response to N-CWS immunotherapy appeared to be associated with the number of macrophages infiltrating into the tumor lesions, and this was confirmed by histological analysis showing that P388 tumors from N-CWS-treated mice were intensively and dominantly infiltrated by macrophages. Furthermore, these were shown to be strongly tumor necrosis factor-positive by immunohistochemical analysis. These findings indicate that macrophages are the main effector cells playing a critical role in the suppression of P388 tumor growth in DBA/2 mice, and that tumor necrosis factor produced by these cells may be involved in the macrophage-mediated cytostatic effect induced by N-CWS. The fact that N-CWS suppressed the growth of weakly immunogenic P388 cells in syngeneic DBA/2 mice even when it was systemically injected would support the clinical potential of this agent. PMID- 1855219 TI - Phase I immunotoxin trial in patients with B-cell lymphoma. AB - Fifteen patients with refractory B-cell lymphoma were treated in a Phase I dose escalation clinical trial with a highly potent immunotoxin consisting of the Fab' fragment of a monoclonal anti-CD22 antibody (RFB4) coupled to chemically deglycosylated ricin A chain. All patients had low, intermediate, or high grade non-Hodgkin's lymphoma. The immunotoxin was administered i.v. in two to six doses at 48-h intervals. The peak serum concentration and the t1/2 were not dose dependent among patients and averaged 1.3 micrograms/ml and 86 min, respectively. Three patients made antibody against A chain, and a fourth made antibody against both A chain and mouse immunoglobulin. Antibody responses were low (less than or equal to 85 micrograms/ml) in three patients and were not detected until 1 mo after treatment. The maximum tolerated dose of the immunotoxin was 75 mg/m2. Dose related toxicities included vascular leak syndrome, fever, anorexia, and myalgia. Dose-limiting toxicities included pulmonary edema and/or effusion, expressive aphasia, and rhabdomyolysis (resulting in reversible kidney failure). There was no evidence of liver dysfunction. Partial responses were achieved in 38% of evaluable patients, and in those patients who had greater than 50% CD22+ tumor cells, 50% of the patients achieved a partial response. Clinical responses were not related to tumor grade and were generally transient, lasting between 1 and 4 mo. PMID- 1855220 TI - Trisomy of rat chromosome 1 associated with mesothelial cell transformation. AB - Identification of specific chromosomal aberrations in transformed mesothelial cells is an important step in elucidating the mechanism of transformation of these cells which are targets for occupational and environmental carcinogens, such as asbestos fibers. Cytogenetic analysis of normal rat mesothelial cell lines revealed that at late passage (p20-p34), trisomy of chromosome 1 was present in greater than 80% of the cells in four spontaneously immortalized lines examined, whereas at early passage (p8-p10), only 15-44% of the cells had trisomy 1. Trisomy of chromosome 1 had increased in the population as a function of passage, suggesting that cells with trisomy 1 had a selective growth advantage under in vitro culture conditions and that this alteration was associated with transformation. A commercially available rat mesothelial cell line (4/4 RM4, ATCC), was also found to have a duplication of a portion of the long arm of chromosome 1. To determine if chromosome 1 alterations have relevance to the transformed phenotype in vivo, a neoplastic cell line was established from a spontaneous rat mesothelioma. At passage 15, trisomy of chromosome 1 was observed in 26% of the metaphases in this line. However, when these cells were injected into nude mice, 99% of the cells from the resulting tumor contained an additional copy of chromosome 1. Therefore, trisomy 1 also conferred a selective growth advantage in vivo and/or was associated with the malignant subpopulation in the tumor derived cell line. These studies suggest that chromosome 1 contains a gene(s) involved in transformation of rat mesothelial cells. PMID- 1855221 TI - The plasminogen activation system in human colon cancer: messenger RNA for the inhibitor PAI-1 is located in endothelial cells in the tumor stroma. AB - Fourteen human colon adenocarcinomas were examined by in situ hybridization for the presence of mRNA for plasminogen activator inhibitor type 1 (PAI-1). All specimens contained PAI-1 mRNA in endothelial cells of some vessels in the stroma immediately surrounding the invasive tumor glands, in granulation tissue, and in some capillaries located under the free luminal surface of carcinomatous epithelium. In addition, a limited number of stromal cells in the cancerous areas located at the periphery of newly formed capillary networks, and presumably representing sprouting endothelial cells, contained PAI-1 mRNA. Cancer cells were devoid of detectable PAI-1 mRNA in all cases. PAI-1 mRNA was not seen in three biopsies of normal colon. Together with previous findings of urokinase-type plasminogen activator and its mRNA being located in fibroblast-like cells in the tumor stroma and mRNA for the urokinase receptor in the cancer cells at invasive foci, these results indicate a complex cooperativity among several cell types in regulation of plasminogen activation in colon cancer. A possible role of PAI-1 in protecting the extracellular matrix in the tumor tissue against degradation and a role in tumor-induced angiogenesis are discussed. PMID- 1855222 TI - Self-diffusion of water in multicellular spheroids measured by magnetic resonance microimaging. AB - Nuclear magnetic resonance microimaging measurements of the self-diffusion coefficient of water in large (greater than 2 mm) EMT-6 multicellular spheroids were performed in order to elucidate diffusion mechanisms in tumors. Pulsed gradient spin echo-imaging methods were developed for measuring diffusion in an intravoxel multicompartment system. The self-diffusion coefficient (at 22 degrees C) for water in the medium (Dm) consisted of only a single diffusion compartment [Dm = 1.99 +/- 0.03 (SE) x 10(-5) cm2/s]. Similarly, the spheroid necrotic center showed a single water diffusion compartment with a self-diffusion coefficient (Dc) significantly lower than that of the medium (Dc = 1.54 +/- 0.05 x 10(-5) cm2/s). The spheroid viable rim region showed two distinct compartments of approximately equal volume, one with a large diffusion coefficient (1.70 +/- 0.12 x 10(-5) cm2/s) and a second with a significantly smaller diffusion coefficient (0.25 +/- 0.01 x 10(-5) cm2/s). We propose that these two experimentally distinguishable compartments correspond to the extra- and intracellular regions, respectively, of the viable rim of the spheroid. Although the diffusion coefficients were significantly different in the medium, the necrotic center, and the viable rim, the activation energy for diffusion was the same in the three regions (0.20 eV). Studies of perfused spheroids at 37 degrees C show the same dependence of the diffusion coefficients on the diffusion filter as observed for unperfused spheroids at 22 degrees C. These results demonstrate the ability of nuclear magnetic resonance microimaging to investigate diffusion at the cellular level, which will lead to a better understanding of microenvironmental regulation in tumors. PMID- 1855223 TI - DNA ploidy by image analysis of individual foci of prostate cancer: a preliminary report. AB - The malignant potential of an individual focus of prostate cancer is difficult to determine. The established pathological features associated with malignant behavior include tumor volume, grade, and invasiveness (local extension or metastasis). We used nuclear image analysis to determine the DNA ploidy value of each cancer in a series of 30 radical prostatectomy specimens from patients with early stage prostate cancer in order to further explore the malignant potential of each separate focus of cancer. The volume, grade, invasiveness (extracapsular extension or seminal vesicle invasion), and zone of origin of each of the 63 separate cancers were determined. The DNA ploidy histogram of 200 cancer cells was compared with 50 normal epithelial nuclei on the same Feulgen-stained tissue sections. Sixty % of the cancers were diploid, and 40% were nondiploid. Ploidy correlated with volume and grade. All cancers less than 0.02 cm3 were diploid; 26% of foci 0.02 to 2.0 cm3 and 82% of foci greater than 2.0 cm3 were nondiploid. There were 16 cancers of transition zone origin ranging in size from 0.02 to 12.1 cm3 and only one (7.3 cm3) was nondiploid. There were 47 cancers of peripheral zone origin (range, 0.01 to 18.98) and 24 (51%) were nondiploid. Eight of the 24 nondiploid cancers were small (less than 1.0 cm3), and two were only 0.03 cm3. We conclude that some very small prostate cancers are nondiploid and that progression of prostate cancer is not a function of volume alone, whereby tumors only acquire full malignant potential at large volumes. Cancers of peripheral zone origin acquire a nondiploid cell population at a smaller volume than do cancers of transition zone origin, further supporting a fundamental difference between cancers arising in these zones. PMID- 1855224 TI - p53 mutations, ras mutations, and p53-heat shock 70 protein complexes in human lung carcinoma cell lines. AB - The p53 tumor suppressor gene is frequently mutated and the K-ras oncogene is occasionally mutated in primary specimens of human lung carcinomas. These mutated genes also cooperate in the immortalization and neoplastic transformation of rodent cells. To determine whether these mutations are necessary for maintenance of the immortalized and/or neoplastically transformed states of human bronchial epithelial cells, the p53 gene and regions of the ras (K-, H-, and N-) genes were sequenced in nine human lung carcinoma cell lines. Detection of p53 mutations by polymerase chain amplification and direct DNA sequencing was corroborated by p53 immunocytochemistry and coimmunoprecipitation of p53 with heat shock protein 70. p53 and ras genes were frequently, but not always, mutated in the carcinoma cell lines. These data are consistent with the hypothesis that multiple genetic changes involving both protooncogenes and tumor suppressor genes occur during lung carcinogenesis. PMID- 1855225 TI - Progression of squamous carcinoma cells to spindle carcinomas of mouse skin is associated with an imbalance of H-ras alleles on chromosome 7. AB - Analysis of benign and malignant mouse skin tumors had previously shown that amplification of a mutant H-ras allele or loss of the normal allele was generally seen only in high grade or spindle cell tumors. The normal:mutant ras gene dosage has been studied directly by polymerase chain reaction amplification of DNA derived from paraffin sections of carcinomas of defined histological types. Some tumors had virtually no signal corresponding to the normal allele and these were invariably spindle cell carcinomas. In four cases where both squamous and spindle cell components could be identified within the same tumor the spindle cell component had a higher mutant:normal gene ratio. Additional experiments on cell lines derived from squamous or spindle cell tumors have demonstrated a good correlation between the ratio of normal:mutant ras and the degree of invasiveness of the cells in in vitro assays. PMID- 1855226 TI - Genetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations. AB - Esophageal squamous cell carcinoma (ESC) samples from patients residing in Uruguay and in Normandy, France, where alcoholic beverages and tobacco smoke are major risk factors, were analyzed for point mutations in the p53 tumor suppressor gene. Among 34 tumors (15 from Normandy and 19 from Uruguay) 15 point mutations in the p53 gene that result in amino acid substitutions or chain termination were identified by polymerase chain reaction amplification of exons 5-8 and direct DNA sequencing. Base substitutions in ESC from these high-incidence areas are dispersed over the midregion of the p53 gene. There are differences between ESC and other types of gastrointestinal cancer in the nature of frequent base substitutions. CpG to TpG transitions were far less prevalent in these ESC than in colorectal tumors, whereas G to T transversions, rarely found in colon cancers, were found in one-fourth of the ESC samples. Base substitutions at A:T pairs constitute an important fraction of ESC p53 mutations, in contrast to mutation patterns in most other types of solid tumors. In contrast to the frequent mutation of the p53 gene in these samples, no mutations in the H-, K-, or N-ras genes were found in 16 tumors from Uruguay by direct sequencing of exons in which transforming mutations are known to occur. A previous study on ras mutations in ESC from France was also negative (M. C. Hollstein et al., Cancer Res., 48: 5119-5123, 1988). The role of distinct etiological factors in generating these differences and the potential for linking patient exposure histories with patterns of p53 mutations in high risk populations are considered. PMID- 1855227 TI - Modification of the growth rates and hypoxic fractions of xenografted A431 tumors by sialoadenectomy or exogenously supplied epidermal growth factor. AB - We studied A431 epidermoid carcinomas xenografted into male nude mice either in the unperturbed state or after either surgical removal of the salivary glands or i.p. injection of exogenous epidermal growth factor (0.2 mg/kg daily for 7 days). The percentage of hypoxic cells in unperturbed tumors was 10.5% (95% confidence limits, 6.6-16.8%). In mice that received epidermal growth factor injections, hypoxic percentages decreased to 3.7% (1.7-7.8%), and tumor growth rates increased. In sialoadenectomized mice, hypoxic percentages increased to 35.2% (27.1-45.6%), and tumor growth rates decreased. These data indicate that the biology of solid tumors can be significantly modified by the host status. PMID- 1855228 TI - The Mary Lasker Conference, on growth factors in hormone-related tumors. PMID- 1855229 TI - Balloon dilatation of intrahepatic biliary strictures for percutaneous extraction of residual intrahepatic stones. AB - Intrahepatic ductal strictures in cholangiohepatitis present an obstacle to successful removal of retained ductal stones via T-tube tracts. We studied the effectiveness of stricture dilatation for stone removal. Fifteen patients with intrahepatic gallstones retained behind strictures underwent balloon dilatation of their strictures to allow stone extraction. All had prior surgical T-tube placement allowing percutaneous access. Balloon dilatation was successful in reducing or eliminating strictures in 86.7% (13 of 15 patients), and complete stone extraction after the successful dilatation was possible in 76.9% (10 of 13 patients). The reasons for failure were impacted stones and acute ductal angulation which prevented passage of catheters. It is concluded that balloon dilatation of intrahepatic biliary strictures is an effective adjunct for extraction of intrahepatic biliary calculi associated with recurrent pyogenic cholangiohepatitis. PMID- 1855230 TI - Percutaneous drainage of postappendectomy abscesses complicated by enteric communication. AB - Four patients with postappendectomy abscesses complicated by enteric fistulae were treated by percutaneous drainage. Sinograms, obtained at the time of the initial drainage, demonstrated communication to the cecum in 3 patients and to the small bowel in 1 patient. Complete cure was attained in 3 patients by percutaneous drainage. In the fourth patient, surgery was performed after 7 days of catheter drainage. Percutaneous drainage of abscesses with enteric communication requires a modified technique, which includes longer-term drainage than for simple noncommunicating abscesses. PMID- 1855231 TI - Treatment of biliary leaks and fistulae by simultaneous percutaneous drainage and diversion. AB - Although biliary fistulae and bilomas are often adequately managed with percutaneous drainage, persistent bile duct leaks are difficult to control. The primary surgical goal in this situation is to decompress the biliary system through diversion of bile flow to facilitate healing of the defect in the bile ducts. We report 3 patients with large biliary duct defects who underwent percutaneous transhepatic cholangiography which demonstrated the site of the biliary leakage. Then, extrapolating the aforementioned surgical tenet to these patients, all 3 were successfully treated with interventional radiologic techniques: simultaneous percutaneous transhepatic biliary diversion to control biliary flow and percutaneous biloma drainage to facilitate closure of the cavity. PMID- 1855233 TI - Mediastinal bronchial artery aneurysm: dynamic computed tomography appearance. AB - Mediastinal aneurysms of the bronchial arteries are uncommon abnormalities with potentially fatal hemorrhagic complications. Their diagnosis is usually made by angiography in emergency situations but computed tomography (CT) scan may depict them in asymptomatic patients. We describe the CT appearance of such an aneurysm detected as an incidental finding in a patient with bleeding bronchiectasis. PMID- 1855232 TI - Treating complications of subclavian vein puncture by embolization of the internal mammary artery. AB - Embolization therapy is reported in 2 patients who had vascular complications following percutaneous subclavian vein catheterization. One had an arteriovenous fistula between the right internal mammary artery (IMA) and the brachiocephalic vein. The other patient presented with a pseudo-aneurysm of the IMA with life threatening hemorrhage and a large thoracic hematoma. A detachable latex balloon was used for occlusion of the arteriovenous fistula in the first patient and a steel spring coil was used to embolize the IMA and the pseudo-aneurysm in the second patient. The lesions were successfully treated on follow-up of 30 months for the first patient and 37 months for the other. PMID- 1855234 TI - Occluding staghorn calcification of the aortic arch and left subclavian artery: case report. AB - A calcified thrombus resembling a staghorn was found in the aortic arch, cast into this shape by the aorta and its branching vessel, the left subclavian, into which it projected for a short distance. Unique, in this case, is the extraordinarily large size of the calcification which was mostly free of the vessel wall, its radiological image, and its location. Digital subtraction angiography led to the diagnosis and was confirmed on computed tomography. PMID- 1855235 TI - Transcatheter hepatic arterial embolization with Avitene in dogs. AB - The hepatic arteries in 36 dogs were embolized with microfibrillar collagen (Avitene) to evaluate the effects on the liver parenchyma. Serial examinations were then conducted over 4 weeks. The dogs were divided into 3 groups: Group 1 received Avitene soaked in saline, Group 2 received decanted Avitene, and Group 3 received Avitene decanted and filtered through gauze. Coagulation necrosis and degeneration of the liver parenchyma was noted in all 3 groups, but was least in Group 3. These results in dogs suggest that gauze filtration of Avitene prior to arterial embolization may also reduce damage to liver parenchyma. PMID- 1855236 TI - A new catheter configuration for selective antegrade catheterization of the superficial femoral artery: technical note. AB - A new 5 F catheter configuration is presented with a very short, 90 degrees angled tip that allows safe catheter tip rotation near the puncture site. This facilitates catheterization of the superficial femoral artery and permits easy conversion of a retrograde into an antegrade guidewire placement after puncture of the common femoral artery. PMID- 1855237 TI - Embolization of a rubber disc from a hemostasis valve: technical note. AB - After coronary angioplasty, a patient experienced a sudden onset of claudication at the side of the vascular entry. Angiography demonstrated an isolated high grade stenosis at the bifurcation of the distal popliteal artery. Thrombolysis and angioplasty were unsuccessful. Surgical exploration showed a rubber disc with attached thrombus to be the cause of obstruction. PMID- 1855238 TI - Surgical and percutaneous management of contralateral thrombus dislodgement following stent placement and dilatation of iliac artery occlusions: technical note. AB - Primary stenting of common iliac artery occlusions was complicated by dislodgement of occluding material to the contralateral common iliac artery in 2 of 59 patients following successful stent placement. In both patients, the complication occurred after balloon dilatation of the inserted self-expanding stent. In the first patient the embolus dislodged to the tibioperoneal trunk and required surgical embolectomy. In the second patient, percutaneous insertion of a self-expanding stent into the contralateral common iliac artery prevented distal embolization. PMID- 1855239 TI - Contemporary venous imaging. AB - Within the past 5 years, venous imaging has rapidly evolved. Ultrasound, predominantly utilizing compression, is now the technique of choice for assessment of extremity venous thrombosis. Issues regarding pulmonary embolism, calf clots, ancillary findings, chronic clots, and the high-risk patient are discussed as they relate to lower extremity deep vein thrombosis. A brief review of upper extremity venous imaging is also included. PMID- 1855240 TI - Angiotensin-II acts centrally to alter renal sympathetic nerve activity and the intrarenal renin-angiotensin system. AB - STUDY OBJECTIVE: The aim was to evaluate the influence that centrally administered angiotensin-II has on the intrarenal renin-angiotensin system and renal sympathetic nerve activity. DESIGN: Renal responses to centrally administered angiotensin-II (10 micrograms) or saralasin (50 micrograms) were measured in anaesthetised rats. The right kidney was vascularly isolated (but neurally intact) and perfused with artificial plasma at either a constant pressure (13.3 kPa) or constant flow (600 microliters.min-1) and renal vascular resistance was measured. Renal perfusate was collected at 10 min intervals after central administration of peptides and intrarenal concentrations of noradrenaline and renin were determined. SUBJECTS: Adult female Sprague-Dawley rats (200-225 g) were used. Rats were given thermal (or sham) lesions of the medial basal forebrain (MBF) 24 h prior to renal perfusion studies. RESULTS: Sham lesioned animals: central administration of angiotensin-II caused an increase in renal vascular resistance and intrarenal noradrenaline concentration in both the constant pressure and constant flow renal perfusion models. Central administration of angiotensin-II increased intrarenal renin concentration in the constant pressure model, while it decreased intrarenal renin concentration in the constant flow model. These effects of intracerebroventricular angiotensin-II were blocked by the concomitant administration of saralasin. Saralasin had no agonist actions on the responses measured. Medial basal forebrain lesioned animals: baseline levels of intrarenal noradrenaline concentration in both the constant flow and constant pressure perfusion models were significantly reduced compared to sham lesioned rats. Baseline intrarenal renin concentration was increased relative to sham lesioned rats in the constant flow perfusion model, but decreased relative to sham lesioned rats in the constant pressure perfusion model. Lesions of the medial basal forebrain block responses to intracerebroventricular angiotensin-II in both models. CONCLUSIONS: Angiotensin II appears to act on neurones within the medial basal forebrain to increase renal sympathetic nerve activity. Renal nerve activity interacts with the prevailing intrarenal pressure to modulate the release of renin. PMID- 1855241 TI - Frequency dependent myocardial potassium fluxes during beta adrenergic stimulation of intact pig hearts. AB - STUDY OBJECTIVE: The aim was to determine the frequency dependent myocardial potassium fluxes of intact pig hearts at control inotropy and during beta adrenergic stimulation. DESIGN - Atrial pacing rate was suddenly raised and decreased by 50 beats.min-1 at control inotropy and during infusion of isoprenaline, 2.5 nmol.min-1, into the left coronary artery. EXPERIMENTAL MATERIAL: Nine anaesthetised pigs (21-33 kg) were instrumented for electric pacing of the right atrium and metabolic and haemodynamic recordings. MEASUREMENTS AND MAIN RESULTS: Myocardial potassium balance was measured by PVC valinomycin electrodes in the left atrial cavity and in a shunt (with flow meter) diverting blood from the coronary sinus to the right atrium. Isoprenaline raised net myocardial potassium flux following the change in pacing rate from 19(14-23) to 38(32-46) mumol.100 g-1.min-1 (median, 95% confidence interval, difference: p = 0.03). The corresponding myocardial potassium flux per beat increased from 0.38(0.29-0.45) to 0.80(0.63-0.97) mumol.100 g-1 (p = 0.03). Accumulated potassium flux increased from 9(8-11) to 17(11-27) mumol.100 g-1, respectively (p = 0.03). CONCLUSIONS: In intact hearts beta adrenergic stimulation doubles the frequency dependent myocardial potassium flux. This component constitutes 22-25% of the ouabain inhibitable potassium flux at both levels of inotropy. PMID- 1855242 TI - Quantitative indices of dispersion of refractoriness for identification of propensity to re-entrant ventricular tachycardia in a canine model of myocardial infarction. AB - STUDY OBJECTIVE: To identify propensity to re-entry in a canine model of 7 day old myocardial infarction, the sensitivity and specificity of five indices of dispersion of refractoriness (ERP) were investigated. DESIGN: With an epicardial patch electrode containing 47 electrodes, ERP was measured by S1-S2 method at each site overlying the infarct. ERP range, maximum adjacent dispersion, difference between mean ERPS of the infarct and normal zones, standard deviation (sigma) of the mean ERP, and sigma/mean ERP X 100 were calculated. EXPERIMENTAL MATERIAL: 42 dogs were divided into three groups; 20 dogs with epicardial functional block on induction of sustained ventricular tachycardia or fibrillation, 10 dogs with inducible ventricular tachycardia or fibrillation but without epicardial functional block, and 12 control dogs without ventricular tachycardia, fibrillation or block. MEASUREMENTS AND MAIN RESULTS: All five indices were significantly greater in the 20 dogs with ventricular tachycardia or fibrillation than in control dogs. A receiver operating characteristic curve analysis of the five indices showed that sigma was the most sensitive and specific index for discriminating these 20 dogs. The sensitivity and specificity of a sigma value greater than 14 ms (the mean value plus two SD of the control dogs) were 70% and 100%, respectively. PMID- 1855243 TI - Increased arterial oxygen content--an important compensatory mechanism in chronic moderate heart failure. AB - STUDY OBJECTIVE: The aim was to determine whether there is a compensatory increase in arterial oxygen content to a hypokinetic circulation in ambulant patients with chronic moderate heart failure caused by dilated cardiomyopathy. DESIGN - Central haemodynamics, arterial oxygen content, arterial haemoglobin concentration, arterial oxygen saturation, and blood gases were measured during a 6 min supine exercise test on a symptom related submaximal workload. At rest, total body haemoglobin was determined. PATIENTS: 19 patients with chronic stable moderate heart failure caused by dilated cardiomyopathy, treated with diuretics and digoxin, were studied. MEASUREMENTS AND MAIN RESULTS: During exercise arterial oxygen content correlated inversely with the cardiac index (r = 0.66, p less than 0.01). The two determinants of arterial oxygen content, arterial haemoglobin concentration and arterial oxygen saturation, also correlated inversely with the cardiac index (r = 0.60, p less than 0.01 and r = 0.70, p less than 0.001 respectively). Cardiac index during exercise correlated inversely with total body haemoglobin (r = 0.73, p less than 0.001). CONCLUSIONS: A hypokinetic circulation during daily living induces an increase in arterial oxygen content in patients with chronic stable moderate heart failure caused by dilated cardiomyopathy. Renal hypoperfusion may play a role in stimulating the erythropoiesis and exertional hyperventilation in raising arterial oxygen saturation. PMID- 1855244 TI - Effect of BN 50739, a new platelet activating factor antagonist, on ischaemia induced ventricular arrhythmias in isolated working rat hearts. AB - STUDY OBJECTIVE: The aim was to investigate the role of platelet activating factor (PAF) in myocardial ischaemia by using BN 50739, a new specific PAF receptor antagonist with a hetrazepine framework. DESIGN: Isolated working rat hearts were subjected to regional ischaemia, induced by ligation of the left main coronary artery for 30 min, followed by reperfusion. BN 50739 was applied at concentrations of 10(-7), 10(-6), 10(-5) and 5 X 10(-5) M, and its effects on the incidence of ischaemia induced and reperfusion induced ventricular tachycardia and ventricular fibrillation and heart functions, such as heart rate, coronary flow, aortic flow, left ventricular developed pressure (LVDP), its first derivative (LVdP/dtmax), and left ventricular end diastolic pressure (LVEDP), were determined. EXPERIMENTAL MATERIAL: Studies were performed on isolated working hearts of male Sprague-Dawley rats weighing 300-360 g. Hearts were perfused with BN 50739 dissolved in dimethylsulphoxide. Control hearts were perfused with the vehicle. MEASUREMENTS AND MAIN RESULTS: Regional ischaemia triggered ventricular arrhythmias showing high incidence between 12 and 20 min with peak appearance at 16 min. BN 50739 induced dose dependent protection against ventricular tachycardia and fibrillation: incidences declined from their respective control values of 91% and 75% to 33% (p less than 0.05) and 8% (p less than 0.05) after exposure to 10(-5) M, and to 25% (p less than 0.05) and 8% (p less than 0.05) after exposure to 5 X 10(-5) M concentrations. Reperfusion of the ischaemic myocardium resulted in an immediate appearance of ventricular tachycardia and fibrillation, but these were not suppressed by the PAF antagonist. Regional ischaemia slightly reduced heart rate, markedly decreased coronary flow, aortic flow, LVDP and LVdP/dtmax, and increased LVEDP. With the exception of LVEDP, these variables were not influenced by the drug. BN 50739, applied at a concentration of 5 X 10(-5) M, reduced LVEDP significantly during the whole ischaemic period. CONCLUSIONS: Under in vitro conditions PAF is likely to be involved in the genesis of ischaemia induced ventricular arrhythmias since BN 50739, a specific PAF receptor antagonist, exerts a protective effect against these rhythm disturbances. This suggests that PAF antagonists may have benefit in the clinical management of acute myocardial ischaemia. PMID- 1855245 TI - Hydrodynamic and energetic aspects of exogenous free fatty acid perfusion in the isolated rat heart during high flow anoxia and reoxygenation: a 31P magnetic resonance study. AB - STUDY OBJECTIVE: The aim was to show differences between the effects of various dietary long chain fatty acids (palmitic, oleic, linoleic, alpha and gamma linolenic acids) perfused in isolated rat hearts subjected to a sequence of high flow anoxia and subsequent reoxygenation. DESIGN: Isolated working rat hearts perfused with selected exogenous fatty acids were allowed an initial 30 min equilibration period followed by 60 min of high flow anoxia and 40 min of reoxygenation. Ventricular function and tissue contents of phosphorylated metabolites were monitored concomitantly using standard procedures and 31P magnetic resonance spectroscopy respectively. EXPERIMENTAL MATERIAL: Hearts were removed from male Wistar rats weighing 350-400 g. Results from eight hearts were pooled for each of the five fatty acids perfused. MEASUREMENTS AND MAIN RESULTS: High coronary flow maintained during anoxia led to an increased extracellular washout of lactate and only to mild intracellular acidosis, limiting myocardial damage by metabolites of anaerobic glycolysis. Under these conditions, marked differences between the classes of perfused fatty acids were observed. Hearts which received oleic acid showed the most depressed ventricular function and a greater depletion in high energy phosphates content. These deleterious effects were completely reversed by the separate administration of two fatty acid metabolism blocking agents, nicotinic acid and oxfenicine. Cardioprotection was enhanced by perfusion of polyunsaturated fatty acids (linoleic acid, alpha and gamma linolenic acids). Hearts perfused either with glucose or with palmitic acid behaved similarly and showed an intermediate functional and metabolic postanoxic recovery. CONCLUSION: This study documents the relation between the chemical structure of exogenous fatty acids used in heart perfusion and their ability to improve or impair postanoxic myocardial recovery. The cardioprotective effect of polyunsaturated fatty acids was documented by simultaneous evaluation of mechanical performance and metabolic response. PMID- 1855246 TI - Role of membrane potential in Ba2+ induced automaticity in guinea pig cardiac myocytes. AB - STUDY OBJECTIVE: The aim was to study in isolated myocardial cells the role of membrane potential in barium induced spontaneous activity and the ionic mechanism of the underlying pacemaker current. DESIGN: The membrane potential and resistance of single myocytes were studied at different voltage levels by means of current and voltage clamp steps in the absence and presence of barium (Ba). EXPERIMENTAL MATERIAL: The membrane potentials and currents of single guinea pig ventricular myocytes were recorded by means of an intracellular microelectrode through which current could also be passed. MEASUREMENTS AND MAIN RESULTS: In the presence of Ba (0.1-0.2 mM), stepwise depolarisations induced a transient overshoot and initiated action potentials followed by an undershoot, diastolic depolarisation and spontaneous discharge. During progressive depolarisations, membrane resistance (Rm) increased, decreased transiently at the end of the action potential, and reincreased during diastole. Stepwise repolarisations had opposite effects. Hyperpolarisations reversed diastolic depolarisation and could unmask oscillatory potentials (Vos). Voltage clamp steps to +20 mV were followed by outward tail currents during which Rm increased. Larger or longer depolarisations were followed by larger outward tail currents at resting potential level. The outward tail current reversed at potentials negative to EK. CONCLUSIONS: In the presence of Ba, applied depolarisation facilitates the induction of spontaneous activity through an interplay between voltage dependent and time dependent Ba block and unblock of gK1, voltage dependent increase in Rm, increased potassium driving force, and negative shift in the slow inward current threshold and sometimes Vos. The pacemaker potential underlying spontaneous activity is due to the slow re-establishment of Ba block of IK1 during diastole. PMID- 1855247 TI - Systemic vasoconstriction induced by inhibition of nitric oxide synthesis is attenuated in conscious dogs with heart failure. AB - STUDY OBJECTIVE: The aim was to test the hypothesis that endothelium dependent vasomotor control is impaired in heart failure. DESIGN AND SUBJECTS: The haemodynamic effects of NG-nitro-L-arginine (NNA), an inhibitor of nitric oxide synthesis, were studied in five dogs with and without pacing induced heart failure. MAIN RESULTS: In healthy dogs, NNA increased total peripheral resistance and arterial pressure, decreasing cardiac output and heart rate. These effects were partially reversed by L-arginine. In dogs with heart failure, NNA did not change any haemodynamic variable. However, L-arginine decreased total peripheral resistance. CONCLUSIONS: These findings support a physiological role for endothelium derived nitric oxide in control of vascular resistance and are in agreement with the hypothesis that endothelium dependent vasomotion may be impaired in heart failure. PMID- 1855248 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 1855250 TI - Calcium pools in sea urchin eggs: roles of endoplasmic reticulum and mitochondria in relation to fertilization. AB - A preparation of sea urchin eggs permeabilized with digitonin (40 microM for 2.5 min) was used to study the kinetic characteristics of the two cellular compartments suspected to play a key role in cellular calcium transfer during fertilization: an ATP-dependent Ca2+ pool (Km = 0.47 microM; Vm = 0.48 nmol/min.mg protein) probably located in the endoplasmic reticulum and a mitochondrial Ca2+ pool (Km = 1.50 microM; Vm = 0.12 nmol/min.mg protein). Fertilization triggered a decrease in the rate of ATP dependent uptake by the non mitochondrial pool (Km = 0.59 microM; Vm = 0.15 nmol/min.mg protein) while it transiently increased the Ca2+ uptake into mitochondria (2 min post fertilization: Km = 2.20 microM; Vm = 0.40 nmol/min.mg protein). Microanalysis studies performed on quickly frozen, freeze substituted and embedded eggs showed a transient Ca2+ enrichment of mitochondria soon after fertilization thus suggesting that mitochondria behave as a Ca2+ sink at fertilization. Results are discussed in relation to the role of endoplasmic reticulum and mitochondria in handling free calcium during the early period following sea urchin egg fertilization. PMID- 1855249 TI - High-resolution measurement and calibration of Ca(2+)-transients using Indo-1 in guinea-pig atrial myocytes under voltage clamp. AB - Spherical atrial myocytes obtained by enzymatic dispersion of hearts from adult guinea-pigs were loaded with the fluorescent Ca(2+)-indicator Indo-1 via patch clamp pipettes. The dialysing solution additionally contained citrate (60 mM) as low-affinity ('linear') Ca(2+)-chelating compound in order to slow intracellular Ca(2+)-transients. Changes in Indo-1 fluorescence under voltage-clamp due to Ca(2+)-entry and/or release from the SR were calibrated using an in vivo procedure to determine the limiting fluorescence ratios. Sample recordings will be presented to demonstrate that components of a [Ca2+]i-transient due to entry via L-type Ca(2+)-channels and due to Ca(2+)-release from the SR can be directly visualized. PMID- 1855251 TI - How many pols does it take to replicate nuclear DNA? PMID- 1855252 TI - Heat shock, stress proteins, chaperones, and proteotoxicity. PMID- 1855253 TI - cDNA cloning and expression of the peptide-binding beta subunit of rat p21ras farnesyltransferase, the counterpart of yeast DPR1/RAM1. AB - Protein farnesyltransferase is a heterodimeric enzyme that attaches a farnesyl group to cysteine in ras proteins and other membrane-associated proteins. The beta subunit contains the recognition site for the peptide substrates, but is inactive in the absence of the alpha subunit. A cloned cDNA for the rat beta subunit predicts a protein of 437 amino acids whose mRNA is present in many tissues. Transfection of the beta subunit cDNA produced farnesyltransferase activity in human kidney cells, but only when it was transfected together with a cDNA encoding part of the alpha subunit. Each of the subunits appeared to be unstable in the transfected cells unless the other subunit was present. The rat beta subunit shows 37% sequence identity with the protein encoded by the yeast DPR1/RAM1 gene, indicating that DPR1/RAM1 is the yeast counterpart of the peptide binding subunit of the mammalian farnesyltransferase. PMID- 1855254 TI - H-2M3 encodes the MHC class I molecule presenting the maternally transmitted antigen of the mouse. AB - Mta, the maternally transmitted antigen of mice, is a hydrophobic, N-formylated mitochondrial peptide, MTF, presented on the cell surface to cytotoxic T lymphocytes by a novel major histocompatibility complex class I molecule, encoded by H-2M3. We have cloned and sequenced two alleles of M3, which differ in their ability to present MTF despite greater than 99% identity in the coding regions. M3 is as divergent from classical, antigen-presenting H-2 molecules as from other class I genes of the Hmt and the Qa/Tla regions. Amino acids critical for folding of class I molecules are conserved in M3. Noncharged amino acids lining the peptide-binding groove and phenylalanine 171 may explain the unique interaction with MTF, and leucine 95 appears critical for immunological activity. PMID- 1855255 TI - Premature initiation of mitosis in yeast lacking RCC1 or an interacting GTPase. AB - A fission yeast mutant is described in which the onset of mitosis is uncoupled from the completion of DNA replication. pim1 (premature initiation of mitosis) cells can undergo mitotic chromosome condensation and mitotic spindle formation without completion of S phase and without the cdc25 mitotic inducer. The M phase kinase is required for pim1-induced mitosis and becomes activated. pim1 encodes a homolog of the human RCC1 nuclear protein. pim1 mutants are fully rescued by overexpression of spi1, a newly identified essential gene whose predicted product shares 81% identity with human TC4. spi1 and TC4 define a new subclass within the "ras-like" GTPase superfamily that is structurally distinct from the ras, rho, or sec4 families. Diploid yeast that carry one wild-type and one disrupted copy of spi1 have multiple satellite nuclei, and mitotic haploidization occurs at very high frequency. spi1 appears to interact with pim1 in the maintenance of a coordinated cell cycle. PMID- 1855256 TI - Homologous pairing in vitro stimulated by the recombination hotspot, Chi. AB - Genetic recombination in Escherichia coli is stimulated at DNA sequences known as Chi sites, 5'-GCT-GGTGG-3'. We describe the in vitro formation of homologously paired joint molecules that is dependent upon this recombination hotspot. Chi dependent joint molecule formation requires RecA, RecBCD, and SSB proteins and a Chi site in the donor linear dsDNA. The donor dsDNA is unwound by RecBCD enzyme, and the invasive strand is generated by nicking at Chi. This Chi-dependent invading strand must contain homology to the recipient supercoiled DNA substrate at its newly formed 3' end for efficient joint molecule formation. Action at Chi generates invasive ssDNA from the 5' but not the 3' side of Chi, suggesting that the nuclease activity of RecBCD enzyme is attenuated upon encountering a Chi site. These results support the view that RecBCD enzyme action can precede RecA protein action and reconcile the seemingly opposing degradative and recombination functions of RecBCD enzyme. PMID- 1855257 TI - Primary structure of the human splicing factor ASF reveals similarities with Drosophila regulators. AB - We described previously the purification of a human protein, called alternative splicing factor (ASF), that can switch utilization of alternative 5' splice sites in an SV40 early pre-mRNA. We now report the isolation of a cDNA, designated ASF 1, that encodes this protein. ASF-1 consists of 248 amino acid residues, including an 80 residue RNA-binding domain at its N-terminus and a 50 residue C terminal region that is 80% serine plus arginine. ASF-1 produced in E. coli can activate splicing in vitro and switch 5' splice-site utilization, establishing that the recombinant protein is sufficient to supply these activities. Analysis of additional cDNAs revealed that ASF pre-mRNA can itself be alternatively spliced, surprisingly, by utilization of a shared 5' splice site and two closely spaced 3' splice sites. Use of the upstream site results in a second mRNA (ASF-2) in which translation of the downstream exon occurs extensively in an alternative reading frame distinct from ASF-1. PMID- 1855259 TI - Sports medicine in the older athlete. PMID- 1855258 TI - The aging of bone and muscle. AB - The purpose of this article has been to summarize the existing body of literature on the changes in the function of muscle and bone that occur as a consequence of aging. Throughout this article, the importance of distinguishing between aging and disuse has been a recurring theme. Much of what had previously been considered aging is now regarded as functional disuse. With aging, muscle undergoes a reduction in size, and consequently strength, which is related to a loss of muscle fibers and a reduction in the size of existing fibers. There may be a selective loss of the Type II, or fast twitch fibers, but this is still under debate. This loss of muscle fibers is more than likely related to the loss of functional motor units. Muscle strength is reduced as a consequence of these changes, but there appears to be little loss in the metal olic potential of the muscle with aging. Exercise training can increase the size and strength of the trained muscles through hypertrophy of both Type I and II fibers and neural alterations but appears to have little effect on decreasing fiber number. Losses of bone start in the third and fourth decade of life, but the pattern of bone loss differs between cortical and trabecular bone, the former being less influenced by menstrual status. Exercise training appears to attenuate the normal decreases in bone with aging and can even lead to small increases in bone density and mass. PMID- 1855260 TI - Climbing and the older athlete. AB - Climbing may be considered appropriate for the older athlete. The requisites, cardiovascular and musculoskeletal fitness, can be attained through training; the skills can be acquired through schools or guide services. Inherent risks can enhance the enjoyment. The motivational psychology for climbing usually reflects positive qualities and attitudes toward life and the environment. With good health, the recreation of climbing can be enjoyed well into the seventh decade of life. Climbing may not be for everyone, but the physical and physiologic benefits, as well as the challenges, are available to the older athlete. PMID- 1855261 TI - The senior tennis player. AB - Mature athletes playing tennis can sustain both acute and chronic injuries. A number of the injuries are related to a gradual loss of flexibility and strength. Much of this is reversible with properly directed conditioning and rehabilitative programs. PMID- 1855262 TI - Cycling and the older athlete. AB - Cycling provides a dynamic form of aerobic and anaerobic fitness to more than 86 million Americans. It provides a freedom that is attractive to individuals of any age, either sex, and any body type. It does not require specialized experience or coordination. In the older athlete, injuries result primarily from overuse or abuse, and are most common in the upper extremity. Such injuries are most often compressive and inflammatory syndromes. These injuries are in marked contrast to those seen in the younger cyclist. Both groups have a low and similar incidence of accident. Overuse injuries can be treated effectively by altering training technique, correcting rider malposition, and decreasing excessive stress, in conjunction with appropriate medical management. Prevention of injury (particularly overuse) is the key to avoiding recurrence. Appropriate frame size, rider position, personalized training techniques, and clothing are essential in the older athlete in whom change is poorly tolerated. Fitness is preserved by regular cycling, possibly by the slowing of the degenerative process, while relieving mental stress and providing "fun sport." PMID- 1855263 TI - Swimming and the older athlete. AB - Swimming is an organized, fast-growing sport and competitive swimmers are now found in abundance in all age groups. Including those athletes who do not compete in formal events (masters swimming program) and those participating in outside events (long-distance, channel swimming, triathlons, and so on), it may be one of the largest participant sports in this country. Injuries to the elite collegiate competitive swimmers have been well-documented. Considerations and injuries to the masters-level swimmer closely mirror those found in the younger athlete, but these injuries reflect the impact of tissue aging (degenerative disease). The preparticipation history and physical examination become more important. We are hopeful that this article will contribute to greater safety and enjoyment among all older swimmers. PMID- 1855264 TI - Running and the older athlete. AB - The beneficial effects of regular, aerobic exercise are well documented. Regular running fulfills the criteria for such a program. Because of the stresses incurred secondary to its impact loading, however, injuries are common. The biological changes that accompany aging can lead to a whole gamut of overuse injuries. To reduce these stresses, proper preparation, clothing, running shoes, training surfaces, and training techniques are recommended. PMID- 1855265 TI - Alpine skiing and the mature athlete. AB - Alpine skiing is a popular sport enjoyed by millions of Americans annually. As the average age of the world population increases, so does the average age of the skier. The ever-increasing older group of skiers adds a new dimension to both the prevention and treatment of ski injuries. Several injuries, if not unique to the older skier, are more common in this group, and familiarity with the causes, treatments, risks, and avoidance of these injuries is essential for proper treatment. It is possible that with proper education, prevention, and physical training, the incidence of these injuries can be decreased to the level of the general population, and skiing will not be more hazardous to the older athlete. PMID- 1855266 TI - Arthritis and athletics. AB - The number of people participating in athletics does not equal the number of people with arthritis. There are no data to support the concern that athletic participation will make the onset of arthritic joints more likely. What is clear is that injuries that occur with athletics can increase the incidence of arthritis. If a patient does develop arthritis secondary to athletics, the treatment is not different than that offered for a spontaneously occurring arthritic joint. If an operation is necessary, the best operation depends a good deal on the goals of the patient. Continued athletic participation may be reasonable as long as the athletic activity is not vigorous and does not involve running and jumping or contact. The recommended athletic activities for patients with arthritis and for those having operations for arthritis are swimming, hiking, bicycling, walking, and golfing. The operations recommended for arthritic patients under the age of 30 should be biologic operations such as fusion or osteotomy. In patients aged 30 to 45, the operation should be correlated to lifestyle and desired level of activity. A biologic operation is better for highly active patients. When patients reach the age of 45 or are older, total joint replacement usually is preferable because of the improved clinical functional results and the decreased stress on surrounding joints with arthroplasty. If patients are older than 60 years, total joint replacement is the operation of choice and usually will include a cemented prosthesis. Some surgeons at this time do prefer cementless total-joint replacement for all patients regardless of age. Patients who have arthritis can have a satisfying athletic and exercise routine if they simply apply common sense to the manner in which they conduct their activities. PMID- 1855267 TI - Exercise participation after menopause. AB - Who should exercise? What exercises should be performed and with what frequency and duration? What benefits can be expected from such exercises? These are some of the questions frequently asked of physicians who care for elderly and post menopausal patients. Data are conflicting, but significant conclusions can be drawn that will help provide the answers to these questions. This article is written to guide physicians' recommendations to their patients regarding postmenopausal exercise. PMID- 1855268 TI - Athletic participation after myocardial revascularization. Possibilities and benefits. AB - Exercise after open heart operation is not only possible but highly desirable. Training increases the efficiency of exercise and therefore decreases myocardial work for any given level of activity. Even before sternal and incisional healing is complete the patient may become physically active. Almost every patient can improve his or her level of fitness safely by following simple guidelines. Exercise treadmill testing is the basis for assessing exercise capacity in cardiac patients. Upper-body exercise is not adequately emphasized in most exercise programs. PMID- 1855269 TI - Musculoskeletal conditioning of the older athlete. AB - A musculoskeletal conditioning program has been shown to result in physical benefits for older individuals. Exercise may influence the rate of bone loss, muscular strength and mass, flexibility, and endurance levels. In turn, these factors may influence the potential for possible future injury. Special precautions should be taken for the older population with emphasis on environmental factors, hydration, and underlying health issues such as cardiorespiratory and orthopedic problems. These concerns may require modifications of the exercise program. PMID- 1855270 TI - The psychology of the aging athlete. AB - Athletes, like other patients, will adhere to their treatment more readily if they believe the physician really understands their needs and cares about them as individuals. The guidelines provided in this article are intended to help the practitioner respond more effectively to each individual patient because effective physician/patient interactions are the very heart of healing. PMID- 1855271 TI - Nutrition of the older athlete. AB - Nutritional needs and dietary goals of the older athlete involve meeting basic physiologic requirements of aging and exercise, promoting weight control, and incorporating guidelines for reducing the risk of chronic disease. Conservative dietary approaches to weight loss in the obese patient and a high-carbohydrate diet for maximum exercise performance are sound approaches, although diets often need to be individualized. Recent dietary recommendations to reduce fat and increase fiber can be applied without risk of compromising nutritional status for most patients. Guidance away from extremes in caloric restriction and in the distribution of calories may help to promote health and the maintenance of exercise activities. Although requirements for certain micronutrients are affected by aging, vitamin and mineral supplements are unlikely to be necessary for healthy adults and should meet basic criteria for safety if they are prescribed. Diet sources of calcium may require attention, although iron requirements are reduced among postmenopausal women when compared with younger athletes. Adequate fluid replacement is essential for athletes of all ages. For the older athlete who is competing in high-intensity endurance exercise, evidence for the usefulness of 4% to 10% carbohydrate-containing sports drinks exists. Little evidence supports the use of ergogenic aids, such as supplements and unusual food products. Resources and personalized guidance from a registered dietitian can be helpful for many older athletes. PMID- 1855272 TI - Penetration of carboplatin and cisplatin into rat peritoneal tumor nodules after intraperitoneal chemotherapy. AB - Platinum distribution was studied in rat peritoneal tumors after i.p. treatment with equimolar doses of carboplatin and cisplatin. Low platinum concentrations (4 ppm) were detected in the periphery of the tumor after carboplatin treatment, whereas no platinum was detected 0.5 mm in from the periphery. In contrast, after cisplatin treatment, high platinum concentrations (29 ppm) were measured in the periphery of the tumor and moderate concentrations (14 ppm) were measured in the center. Only following increased carboplatin doses were low platinum concentrations detectable in the tumor. The total platinum concentration in the tumors was determined after equimolar administration of both drugs. In all, 7 times more platinum was detected after cisplatin treatment than after carboplatin treatment, and 10 times more carboplatin than cisplatin had to be injected to obtain comparable platinum concentrations in the tumors. When single cells were incubated with equimolar concentrations of carboplatin and cisplatin, 6-7 times more platinum was found in cells treated with cisplatin. However, pharmacokinetic studies favored i.p. administration of carboplatin because the clearance of this compound from the peritoneal cavity, expressed as t1/2 beta, was lower than that of cisplatin (239 vs 78 min), resulting in an AUC in the peritoneal cavity for both total and ultrafiltered drug that was almost 3 times higher for carboplatin than cisplatin. The AUC for ultrafiltered carboplatin in plasma was 2-fold that for cisplatin (2,801 +/- 210 vs 1,334 +/- 431 microM m). The present study demonstrated that in spite of the pharmacological advantages of carboplatin, its capacity to penetrate into peritoneal tumors and tumor cells is far lower than that of cisplatin. PMID- 1855273 TI - L-cysteine prodrug protects against cyclophosphamide urotoxicity without compromising therapeutic activity. AB - 2(R,S)-D-ribo-(1',2',3',4'-Tetrahydroxybutyl)-thiazolidine-4(R)-ca rboxylic acid (RibCys) is a prodrug of L-cysteine that releases the sulfhydryl amino acid after nonenzymatic ring opening and hydrolysis. The L-cysteine then elevates glutathione (GSH) levels by stimulating its biosynthesis. RibCys was investigated for its ability to protect CDF1 mice from the potent urotoxicity of cyclophosphamide (CTX) without compromising the therapeutic utility of the drug. RibCys induced a significant reduction in weight loss of the animals and in bladder inflammation at 48 h after CTX administration; however, bladder tissue remained inflamed as compared with that in controls. Bladder histology also showed some pathological changes in the presence of RibCys. In contrast, all parameters of toxicity (body weight loss, bladder inflammation, and pathological abnormalities) had been virtually reversed by day 21 after administration. In tests against L1210 leukemia, RibCys did not interfere with CTX anticancer activity. From these preliminary studies, RibCys appears to be a likely candidate for protecting against long-term CTX toxicity, perhaps reversing the original damage caused by a very high dose, without compromising the therapeutic utility of the alkylating agent. PMID- 1855274 TI - The mechanism of differential sensitivity to methotrexate of normal and malignant human epidermal cells. AB - Squamous carcinoma cells are much more sensitive (greater than 10(4) times) to the cytotoxic effects of methotrexate (MTX) and 5-fluorodeoxyuridine (FUDR) than are normal human keratinocytes as measured by cell growth. Among the drugs tested, this phenomenon was found to be specific for MTX and FUDR, since arabinosylcytidine (ARA-C), 13-bis-chloroethylnitrosourea (BCNU), and daunomycin failed to show differences in inhibition between the normal and malignant cell lines. Drug uptake studies did not reveal a significant difference in MTX intracellular levels between malignant and normal epidermal cell lines at 60 min. Thymidine (TdR) salvage was assessed by examining the effects of the presence of 3 microM TdR on MTX-induced cytotoxicity. On the withdrawal of TdR, normal cells demonstrated an increased level of inhibition amounting to 4 orders of magnitude, whereas the squamous-cell carcinoma cells showed no change in sensitivity. Interestingly, the immortal nontumorigenic keratinocyte line (NM-110) was similarly not rescued by the addition of TdR. The high degree of sensitivity TO MTX shown by squamous-cell carcinoma (SCC) and NM-110 cells is attributable to a significant diminution of their ability to use exogenous TdR as compared with that of normal keratinocytes and might be indicative of a biochemical change associated with cellular immortality. PMID- 1855277 TI - A pharmacokinetic study of prednimustine as compared with prednisolone plus chlorambucil in cancer patients. AB - The pharmacokinetic characteristics of prednisolone and of chlorambucil and its beta-oxidized metabolite, phenylacetic mustard (PAM) were studied in plasma after the oral administration of 200 mg prednimustine (Sterecyt) and a regimen consisting of 20 mg prednisolone plus 20 mg chlorambucil, respectively. A total of 12 cancer patients completed this trial. The drugs were given in a cross-over study as single doses, and serial plasma samples were collected for 32 h. Chlorambucil and PAM were assayed by a gas chromatographic/mass spectrometry method and prednisolone, by radioimmunoassay. The median relative availability of the prednisolone and chlorambucil moiety in prednimustine was 19% and 16%, respectively. Prednisolone, as well as chlorambucil and PAM, appeared later and at a significantly lower concentration in plasma after treatment with prednimustine as compared with the mixture of chlorambucil and prednisolone. We also found that the elimination phase of chlorambucil and PAM in plasma is prolonged after the administration of prednimustine as compared with chlorambucil per se. In contrast, the elimination of the prednisolone moiety of prednimustine and that following the administration of a plain prednisolone tablet did not seem to differ. The modified plasma profile of the alkylating components following prednimustine administration may be important for the clinical efficacy of prednimustine. PMID- 1855275 TI - Antibodies against cisplatin-modified DNA and cisplatin-modified (di)nucleotides. AB - Cytotoxic effects of cis-diamminedichloroplatinum-(II) (cis-DDP) are thought to be mediated by binding to DNA. Studies on binding of cis-DDP to cellular DNA rely heavily on the availability of specific antibodies. We therefore raised and characterized four rabbit antisera: one against cis-DDP-modified DNA (antiserum NKI-A59) and three others against the cis-DDP-modified (di)nucleotides cis Pt(NH3)2d(pApG) (NKI-A68), cis-Pt(NH3)2d(GMP)2 (NKI-A10), and Pt(NH3)3dGMP (NKI A39). Reactivities to platinum compounds were determined in an enzyme-linked immunosorbent assay (ELISA) and in a quantitative immunocytochemical assay. In the ELISA, NKI-A59 showed a high affinity for DNA heavily substituted with either cis-DDP or CBDCA [cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II)]; amounts of platinum per well giving 50% inhibition (IA50) were as low as 15 and 76 fmol, respectively. NKI-A59 also showed affinity to cis-DDP-modified poly[d(G C)].poly[d(G-C)], poly(dC), and poly(dG). No affinity was found for trans-DDP [trans-diamminedichloro-platinum(II)]-modified DNA, enzymatically digested cis DDP-DNA, or cis-DDP-DNA, or cis-DDP-modified poly(dA).poly(dT), oligo(dA)15.oligo(dT)15, oligo(dG)21, oligo(dG)42, or oligo(dAAAG)10. The efficiency of binding to cis-DDP-DNA decreased with decreasing DNA modification levels. Although other cis-DDP-DNA- and cis-DDP-(di)nucleotide-specific antisera have been identified, NKI-A59 is the first antiserum described that is suitable for the in situ detection of cis-DDP-DNA adducts at clinically relevant platinum levels. Adduct-specific immunostaining signals in cultured RIF-1 cells or rat liver paralleled platinum-DNA binding as measured by atomic absorption spectroscopy. The antisera NKI-A68, NKI-A10, and NKI-A39 showed high affinity for their corresponding haptens and varying affinity for non-hapten cis-DDP-DNA adducts. Their affinity for digested cis-DDP-modified DNA was up to 30 times that for intact cis-DDP-DNA. Neither NKI-A68 nor NKI-A10 resulted in specific immunocytochemical staining of cis-DDP-DNA adducts. We conclude that NKI-A68, NKI A10, and NKI-A39 are suitable for platinum-DNA adduct analysis of digested DNA in ELISA and that NKI-A59 is suitable for platinum-DNA adduct detection at the single-cell level using immunocytochemical methods. PMID- 1855276 TI - Antitumor activity of a camptothecin derivative, CPT-11, against human tumor xenografts in nude mice. AB - The antitumor effects of the camptothecin (CPT) derivative CPT-11, 7-ethyl-10-[4 (1-piperidino)-1-piperidino]-carbonyloxycamptothecin , were tested on human tumor xenografts in nude mice. CPT-11 showed antitumor activity higher than that of Adriamycin, 5-fluorouracil, or futraful, with little or no reduction of body weight being observed in the mice. The growth of colon adenocarcinoma Co-4 was significantly inhibited after a single i.v. injection of CPT-11 at 25, 50, or 100 mg/kg. The single i.v. injection was also significantly effective against mammary carcinoma MX-1 and gastric adenocarcinoma St-15. All of the mice bearing MX-1 tumors were cured by the administration of CPT-11 every 4 days for a total of three treatments at a total dose of 200 mg/kg given i.v. or of 400 mg/kg given p.o. Three i.v. or oral treatments were also effective against Co-4, St-15, gastric adenocarcinoma SC-6, and squamous-cell lung carcinoma QG-56. To achieve the same efficacy attained by i.v. injection, however, oral doses 2-4 times higher than the i.v. doses were required. When the total dose was fixed at 100 mg/kg, a triple i.v. injection was most effective, followed by a single i.v. injection and, finally daily p.o. administration for 10 days. Although SN-38 (7 ethyl-10-hydroxycamptothecin), a metabolite of CPT-11, showed much stronger cytotoxic activity in vitro than did CPT-11, its antitumor effects were similar, if not inferior, to those of CPT-11 in vivo at the same dose level. CPT-11 was converted into SN-38 by human tumors, but the sensitivity of these tumors to CPT 11 in vivo was independent of their ability to produce SN-38. These results suggest that CPT-11 may be clinically effective, depending on the schedule of administration, but that its effectiveness is not related to the ability of the tumor to produce SN-38. PMID- 1855278 TI - Unaltered pharmacokinetics after the administration of high-dose etoposide without prior dilution. AB - The pharmacokinetics of etoposide following a new method of administration was determined. Undiluted etoposide was given at a dose of 30 mg/kg as part an intensified conditioning regimen prior to bone marrow transplantation. A terminal half-life of 3.4 +/- 0.7 h and a volume of distribution of 15.4 +/- 9.6 l were found (n = 8); the AUC was 764 +/- 302 micrograms h ml-1. As compared with those obtained in other pharmacokinetic studies using etoposide diluted in normal saline, our data reflect full systemic bioavailability and unaltered pharmacokinetics. The application of undiluted etoposide makes the therapy easier and less time-consuming and avoids a high fluid volume and a high saline load. PMID- 1855279 TI - Case report of metastatic familial pheochromocytoma treated with cisplatin and 5 fluorouracil. AB - We report on a rare case of malignant pheochromocytoma in a patient with a family history of this disease. After three cycles of treatment with cisplatin and 5 fluorouracil, a decrease in the need for antihypertensive treatment occurred, which lasted almost 2 years despite the discontinuation of chemotherapy. The patient showed an objective response, which was technically a minor response, although in this slow-growing tumor it was of major clinical significance. This chemotherapy regimen may play a role in the management of malignant pheochromocytoma. PMID- 1855280 TI - Double-blind, randomized crossover study of metoclopramide and batanopride for prevention of cisplatin-induced emesis. AB - We conducted a double-blind, randomized crossover study to compare the toxicity and antiemetic efficacy of the 5-hydroxytryptamine3 receptor antagonist batanopride with that of metoclopramide in 21 chemotherapy-naive patients receiving at least 70 mg/m2 cisplatin. The study was terminated when hypotension was observed following the infusion of batanopride at other institutions testing similar drug schedules. Although we observed no hypotension following treatment with batanopride in this trial, we did note asymptomatic prolongation of the corrected QT interval (QTc), PR interval, and QRS complex on the EKG in the batanopride arm. Of 15 evaluable patients, 8 experienced less than or equal to 2 episodes of emesis within 24 h of the first batanopride infusion, whereas 9/15 subjects experienced less than or equal to 2 emetic episodes following the administration of metoclopramide. Overall, the evidence suggests that this dosing schedule for batanopride may be too toxic for clinical use. PMID- 1855281 TI - Single-dose i.v. dexamethasone--an effective anti-emetic in cancer chemotherapy. AB - We conducted a randomised, single-blind, placebo-controlled crossover study to assess the efficacy of a single i.v. dose of 20 mg dexamethasone as an anti emetic in 31 patients receiving cancer chemotherapy. Patients receiving dexamethasone experienced significantly less nausea and vomiting (P less than 0.001 and P less than 0.01, respectively), and appetite and activity were normal in a majority of the treated group. Side effects were insignificant. We conclude that single-dose dexamethasone given i.v. at a dose of 20 mg is a safe and effective anti-emetic for patients receiving cancer chemotherapy excluding cisplatin. PMID- 1855282 TI - Bone protein and peptide assays in the diagnosis and management of skeletal disease. AB - The measurement in blood of bone proteins is an important adjunct to imaging procedures for clinical assessment of the skeleton. The discovery of new bone proteins and their structural characterization has led to immunochemical procedures of improved sensitivity and specificity for their quantification. An appreciation of the advantages and disadvantages of these evolving methodologies will assist in their clinical application. PMID- 1855283 TI - Cholesterol distribution between high-density-lipoprotein subfractions HDL2 and HDL3 determined in serum by discontinuous gradient gel electrophoresis. AB - We used discontinuous gradients of polyacrylamide gel to determine the high density-lipoprotein (HDL) subfractions HDL2 and HDL3 of serum lipoproteins. Serum (40 microL) prestained with Sudan Black was electrophoresed in cylindrical tubes over successive layers of 3.5%, 6%, 13%, and 17.5% acrylamide gels in a Tris.glycine buffer (3-4 h, 300 V). Very-low- (VLDL) and low-density lipoprotein (LDL) were retained by the 3.5% and 6% gels. HDL2 was concentrated at the interface between the 13% and 17.5% gels, and HDL3 migrated into the 17.5% gel. The distribution between HDL2 and HDL3 was obtained by densitometric scanning. Application of the respective percentages to HDL cholesterol assayed after phosphotung-state-Mg2+ precipitation of VLDL and LDL gave calculated concentrations of HDL2 and HDL3 cholesterol. The calculated values for HDL2 cholesterol were in excellent agreement with those for HDL2 isolated by ultracentrifugation (r = 0.920 for n = 120 sera; differences nonsignificant by Student's paired t-test). Besides being highly discriminating, the method is rapid, easily performed, and economical. PMID- 1855284 TI - Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. AB - Specific antibody synthesis in brain could be detected with maximal sensitivity by combining an advanced enzyme immunoassay with a sophisticated evaluation method that involves calculating the ratio between the cerebrospinal fluid (CSF)/serum quotients for specific antibodies (Qspec) and total IgG (QIgG). This Antibody Index (AI = Qspec/QIgG) discriminates between a blood-derived and a pathological, brain-derived specific antibody fraction in CSF and takes into account individual changes in blood/CSF barrier function. For local synthesis of polyclonal IgG in the central nervous system (QIgG greater than QLim), we propose the correction AI = Qspec/QLim (QLim represents that IgG fraction in CSF originating only from blood, calculated from the individual albumin quotient of a single patient). The normal reference range for the AI was between 0.7 and 1.3 (n = 250 control patients for each antibody species). Values of AI greater than or equal to 1.5 indicated a local specific antibody synthesis in the central nervous system. Sensitivity and precision were greatest if we analyzed the virus-specific antibodies in CSF and serum simultaneously with an enzyme immunoassay in continuous concentrations (arbitrary units) instead of titer steps. We have applied the method successfully to antibodies to measles, rubella, herpes simplex, varicella-zoster, human immunodeficiency virus (HIV), and cytomegalovirus, and to anti-Toxoplasma or -Borrelia antibodies. Clinical relevance is demonstrated for an acute zoster virus infection (monospecific response), chronic diseases such as HIV encephalitis with acute opportunistic Toxoplasma infection, and multiple sclerosis (secondary polyspecific response). PMID- 1855285 TI - Determination of serum cholesterol by isotope dilution mass spectrometry with a benchtop capillary gas chromatograph/mass spectrometer: comparison with the National Reference System's Definitive and Reference Methods. AB - We developed an isotope dilution mass spectrometric cholesterol method with [25,26,27-13C]cholesterol as internal standard and a benchtop gas chromatograph/mass spectrometer (GC/MS) that is much easier and less time consuming than previously described Reference and Definitive Methods for cholesterol. The internal standard, cholesterol standards, and unknown specimen are delivered volumetrically with an automated dilutor and the saponifying reagent. After saponification, extraction, and derivatization, specimens are injected into a benchtop quadrupole MS with an autosampler. Unknown cholesterol concentrations are calculated automatically by comparing the peak area ratio of the m/z = 368, 371 ion pair with the ratios for the cholesterol standards (0 to 12.93 mmol/L). We found within-run and day-to-day (overall) imprecision of 0.44% and 0.95%, respectively, when specimens were assayed singly. In several lyophilized and frozen Standard Reference Material (SRM) pools, cholesterol results with our GC/MS method averaged 0.4% less than the National Institute for Standards and Technology definitive GC/MS result performed about three years earlier. Our GC/MS results averaged 1.3% and 2.0% less than results by the National Reference System (NRS) Abell-Levy-Brodie-Kendall (ALBK) results from clinical specimens and the SRM pools, respectively. These results are consistent with the previously reported bias between the NRS Reference and Definitive Methods and the 0.1% per year decrease in cholesterol concentrations in SRM pools as determined by GC/MS analysis. These results further emphasize the small but consistent bias between cholesterol results by isotope dilution mass spectrometry and the ALBK Reference Method, the latter being the basis for the National Cholesterol Education Program guidelines and population reference values. PMID- 1855286 TI - Time-integrated measurement of corticosteroids in saliva by oral diffusion sink technology. AB - Saliva, as a medium for assessing adrenocortical function in humans, has many advantages and a few distinct disadvantages. Interpretation of measurements of saliva cortisol is complicated by the contamination of saliva by steroid-binding proteins from blood plasma, enzyme activity in the salivary gland that converts cortisol to cortisone, and the amplification in saliva of the episodic fluctuations in systemic cortisol concentrations. We describe a new measurement technology that rejects artifacts from contamination of saliva by plasma protein, provides for measurement of both cortisol and cortisone, and integrates episodic fluctuations in concentration over a period of hours. This oral diffusion sink technology may greatly enhance the reliable interpretation of corticosteroid concentrations measured in saliva. PMID- 1855287 TI - Isolation and characterization of zinc coproporphyrin I: a major fluorescent component in meconium. AB - We isolated a substance from an organic extract of meconium (in neutral pH) that exhibited a porphyrin-like fluorescence peak at 580 nm on excitation at 405 nm and deduced its structure. Spectrometric data suggest that the substance is not free coproporphyrin I or free coproporphyrin III, but is a chelate of coproporphyrin I with Zn2+. We also detected a chelate of coproporphyrin III with Zn2+ by HPLC. These substances may be useful as new indicators of the presence of meconium. PMID- 1855288 TI - Rapid and specific enzyme immunoassay of serotonin. AB - A new, highly sensitive enzyme immunoassay (EIA) of serotonin (5HT) is described. The assay is based on the competition between N-succinyl-glycinamide-serotonin (N SGA-5HT, obtained by acylation of the 5HT in the sample to be assayed) and an enzymic tracer, N-succinyl-5HT-acetylcholinesterase, for binding to rabbit polyclonal antibody coated onto the wells of microtiter plates. The antibody is directed against an immunogen obtained by coupling N-succinyl-5HT to glycyl bovine serum albumin. The EIA permits the accurate measurement of as little serotonin as 0.5 nmol/L (1.8 pg per well) in blood, plasma, serum, cerebrospinal fluid, urine, platelets, and other tissues, with no significant cross-reactivity with other compounds. The results obtained correlate well with those obtained by HPLC after extraction. The assay has the advantage of permitting the measurement of 5HT in up to 500 samples in as little as 3 h. PMID- 1855289 TI - Micro-quantification of cyclosporine and its metabolites and determination of their spectral absorptivities. AB - We report a micromethod for the analysis of cyclosporine (CsA), based on quantification of its constituent amino acids. The amino acids were released by gas-phase hydrolysis, derivatized with fluorenylmethyl chloroformate, and separated and analyzed in a reversed-phase HPLC system. The imprecision (CV) of the amino acid analysis was less than 4%, and several determinations of the amount of standard CsA were within 1% of the weighed material. The detection limits (signal-to-noise ratio = 2) were 500 fmol for ultraviolet detection and 100 fmol for fluorescence detection. We also used this method to determine the ultraviolet absorptivities of CsA and five metabolites at 210, 214, and 230 nm. The molar absorptivity of most metabolites was about 10% higher than that of CsA, although the metabolite that was oxidized to a carboxyl group on the terminal carbon of N-methyl-butenyl-methyl-threonine (AM1A) had a molar absorptivity about 40% higher than that of CsA. PMID- 1855290 TI - Combi scheme: new combined internal/external quality-assessment scheme in The Netherlands. AB - The Dutch Foundation for Quality Assessment in Clinical Chemistry (SKZL) is the professional organization that conducts external quality-assessment schemes in The Netherlands. However, such schemes in fact assess the performance of the internal quality-control systems of the participating laboratories. In this paper we describe a new concept, relating the data for internal control materials with those for external samples and thereby leading to a combined external/internal scheme (Combi). The statistical principles underlying the Combi scheme are discussed and examples of the graphical presentation of the results are shown. Because the laboratory data are transmitted over the public telephone system to the computers of the SKZL, we also describe the principles of the data communication. At two-month intervals a statistical presentation is sent to all participants. The central database is updated daily with the received results, making possible an on-line consultation regarding the statistics of the accumulated findings of the control materials in use. PMID- 1855291 TI - Toxicological screening of drugs by microbore high-performance liquid chromatography with photodiode-array detection and ultraviolet spectral library searches. AB - We use ultraviolet data, acquired with a photodiode-array detector coupled to a reversed-phase liquid-chromatographic system, to identify unknown drugs in plasma samples of acutely poisoned patients. Both retention time and spectra of the peaks obtained with a microbore Hypersil ODS column under gradient elution are compared with a library of approximately 350 compounds. We present our three-year experience with this system, which identifies drugs in less than 1 h, with a high degree of confidence. PMID- 1855292 TI - Assessing acute parathyroid responsiveness in hemodialysis patients by measuring intact parathyrin in pre- and post-dialysis serum. AB - We measured pre- and post-dialysis concentrations of ionized calcium (iCa) in whole blood, total calcium (tCa) in plasma, and intact parathyrin (PTH) in serum of 19 patients undergoing maintenance hemodialysis. Plasma tCa was inappropriately increased relative to iCa in 63% of the specimens; the iCa correlated with the PTH concentration in 12 of 19 pre-dialysis specimens, whereas tCa correlated with PTH in only five patients. During dialysis, 16 patients had analytically significant changes in iCa (i.e., exceeded the analytical imprecision of 0.04 mmol/L). Pre- and post-dialysis concentrations of PTH were normal in six patients, four of whom showed a detectable response to changes in iCa. Ten patients had increased PTH in at least one specimen; of these, eight had responsive parathyroid glands. Five of the 16 patients had an increased set point for calcium. The minimal PTH responses of two patients suggested refractory hyperparathyroidism. We conclude that routine estimation of iCa, rather than tCa, in dialysis patients markedly improves the identification of patients at risk for secondary hyperparathyroidism, and that measurement of intact PTH in pre- and post-dialysis serum offers a simple means of assessing parathyroid responsiveness in dialysis patients. PMID- 1855293 TI - Rapid detection and initial characterization of genetic variants of human serum albumin. AB - We have studied the detection and classification of genetic variants of human serum albumin by electrophoresis. Samples from 10 patients who were heterozygous for eight different albumin variants were studied by two methods. In agarose gel electrophoresis, each of these variants has an abnormal mobility and can be classified on the basis that structural changes at the N-terminus abolish 63Ni binding. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole serum, glycosylated variants are easily detected because of their greater apparent molecular mass. PMID- 1855294 TI - Simple method for preparing a concentration gradient of serum components by freezing and thawing. AB - We created a simple method for obtaining a series of successively more concentrated samples from a serum without changing the ratio of its components. We froze a pooled serum and then allowed it to thaw undisturbed. The serum components formed a gradient of increasing concentration from the top of the sample to the bottom. We found that (a) in test results, each fraction of serum in the gradient showed almost the same relative concentrations of components (i.e., inorganic and organic compounds, proteins, metals, and hormones), irrespective of atomic or molecular mass; (b) the concentration gradient depended on the thawing temperature but not on the freezing temperature; (c) when we thawed the frozen sample with centrifugation, the slope of the concentration gradient increased with increasing centrifugal force; (d) when the thawed sample was fractionated into 10 fractions from the top to the bottom, the original serum concentration was always maintained between the sixth and seventh fractions from the top; and (e) the concentration gradient became steeper with repeated freezing and thawing. By using this method, one can easily prepare serum samples at gradients of concentration useful in the clinical laboratory, although the mechanism of gradient formation is still unclear. PMID- 1855295 TI - Modified enzyme-based colorimetric assay of urinary and plasma oxalate with improved sensitivity and no ascorbate interference: reference values and sample handling procedures. AB - The measurement of oxalate in urine and plasma continues to be difficult, particularly in the presence of ascorbate. We have modified and validated a colorimetric assay involving the use of oxalate oxidase (EC 1.2.3.4). Modification of an HPLC spectrophotometric detector improved sensitivity (to as much as 1000-fold that of conventional spectrophotometers) and allowed measurement of oxalate concentrations less than 1 mumol/L. This provided more than enough sensitivity for measurement of normal concentrations of plasma oxalate. We established reference values for oxalate concentrations in urine and plasma, studied sample handling, and established conditions to avoid ascorbate interference in urine and plasma measurements. Mean analytical recovery of [14C]oxalate from plasma to the filtrate was 86 (SD 10)%; recovery of unlabeled oxalate from filtrate was 87 (SD 9)%. Urinary oxalate excretion rates in apparently healthy controls were 0.11-0.46 mmol/24 h. Plasma concentrations in control subjects were 2.5 (SD 0.7) mumol/L, similar to concentrations determined by recent gas chromatographic and isotope dilution methods. Frozen and acidified urine samples showed no interference from ascorbate when excess ascorbate was avoided. Ingestion of 2 g of ascorbate daily did not increase urinary oxalate in healthy control subjects, but during storage ascorbate was converted to oxalate in all conditions tested. PMID- 1855296 TI - One-step chromogenic equivalent of activated partial thromboplastin time evaluated for clinical application. AB - We evaluated the clinical usefulness of a recently developed semi-automated one step chromogenic equivalent of activated partial thromboplastin time (APTT; Behring). This simple test is easily adaptable for automation. Generally, the results with this chromogenic one-step APTT were at least as precise as those obtained with comparative coagulometric methods. The chromogenic one-step APTT showed, both in vitro and in vivo, adequate sensitivity to congenital intrinsic factor deficiency but no sensitivity to Factor VII deficiency. Unlike a two-step coagulometric APTT (Dade), the one-step chromogenic APTT seemed sensitive to activation products of the contact system, which are present in immunoadsorbed factor-deficient plasma. The in vitro sensitivity of the chromogenic APTT to heparin was comparable with that of a coagulometric APTT, but the sensitivity to heparin in patients' samples differed slightly. The chromogenic APTT is relatively insensitive to anomalies in the fibrinogen-fibrin conversion. Finally, we observed discrepancies between the chromogenic and coagulometric APTT results for plasma of patients with disseminated intravascular coagulation. We conclude that this one-step chromogenic APTT warrants further evaluation for possible use as a routine test for the clinical laboratory. PMID- 1855297 TI - Stabilization of turbidimetric immunoassay by covalent coupling of antibody to latex particles. AB - Turbidimetric immunoassay is commonly used to quantify serum proteins. Latex particle enhancement of this type of assay has been primarily associated with increasing assay sensitivity. However, covalent coupling of an antibody to a latex particle can offer other advantages that are also pertinent in measurement of high concentrations of analytes. By using a common antibody with IgG as a model analyte, we describe the development of a nonenhanced and a latex-particle enhanced turbidimetric assay for measuring serum IgG. Both assays show adequate analytical recovery and parallelism, and results compare well with those by rate nephelometry. The latex-enhanced assay has equivalent sensitivity, working range, and interassay precision, but much greater signal change and calibration stability than the nonenhanced assay. In addition, with latex particles, less antiserum is needed. Coupling antibodies to latex particles offers considerable advantages, even when an improved assay detection limit is not required. PMID- 1855298 TI - Clinical validation of a second-generation fructosamine assay. AB - The serum fructosamine assay, used to monitor short-term clinical glycemic control, reportedly has several technical drawbacks. However, technical improvements have resulted in a new second-generation assay of fructosamine. We evaluated this second-generation assay (from Roche Diagnostics) in 529 nondiabetic and diabetic patients and found a highly significant correlation with results of the first-generation assay (r = 0.91, P less than 0.001). Use of the second-generation assay with samples from patients classified on the basis of glycemic control according to their glycohemoglobin (GHb) values, enabled us to discriminate between the nondiabetics, diabetics with "good/moderate" control (i.e., GHb less than 10%), and diabetics with "poor" control (GHb greater than or equal to 10%). We evaluated the validity of the second-generation assay to assess short-term glycemic control in 23 non-insulin-dependent diabetic patients who participated for 10 weeks in an intensive intervention program designed to rapidly normalize the clinical glycemic profile. Results correlated significantly with the one-week average capillary blood glucose concentration (CBG) and with the three-week average CBG in all 23 patients. In addition, the second-generation fructosamine assay results demonstrated a significant decrease at each week of study, as did the average CBG. Results of the first- and second-generation assays correlated significantly at each week of study. GHb correlated significantly with both the second- (r = 0.78, P less than 0.001) and first-generation fructosamine assay results (r = 0.77, P less than 0.001) for the baseline blood samples of the intervention study, but this correlation decreased (to r = 0.35, P = 0.09 and r = 0.34, P = 0.09, respectively) by the conclusion of the study. PMID- 1855299 TI - Detection of human apolipoprotein E3, E2, and E4 genotypes by an allele-specific oligonucleotide-primed polymerase chain reaction assay: development and validation. AB - A polymerase chain reaction (PCR) assay has been developed and validated by using allele-specific oligonucleotide (ASO) primers to specifically amplify E3, E2, and E4 polymorphic sequences of the human apolipoprotein E (apo E) genes. Degenerate ASOs containing one or two additional 3' mismatches provided greater specificity than did ASOs containing a single mid-sequence or 3' allele-specific mismatch with plasmid pEB4 or genomic DNA as template. Optimal specificity and efficiency of amplification did not correlate with primer annealing conditions, whether determined theoretically or via oligo-melting experiments. Pre-cycling denaturation times and high cycling denaturation temperatures were also required for optimal amplification, presumably because of the high G:C content (75-85%) of apo E gene sequences. Conditions permissive for amplification and discrimination with plasmid DNA did not transpose favorably to amplification from human genomic DNA from peripheral blood leukocytes; the latter required nested primer reactions. These data may be valuable in predicting PCR assay conditions for other G:C-rich sequences containing polymorphic sequence differences. The assay described is both more accurate and rapid (24 h) than previously described methods for phenotyping or genotyping human apo E from blood specimens. PMID- 1855300 TI - Effects of serum-isolated vs synthetic bilirubin-albumin complexes on dye-binding methods for estimating serum albumin. AB - Bush and Reed reported (Clin Chem 1987;33:821-3) that the reaction of albumin with bromcresol purple but not with bromcresol green underestimated the concentration of albumin in synthetically obtained bilirubin-albumin (Bd) by 29%. Their unproven assumption was that chemically synthesized Bd behaved in a manner indistinguishable from the natural Bd in icteric serum. Here we verify that Bd, whether synthetically obtained or isolated from serum, causes an underestimation of albumin in the bromcresol purple but not in the bromcresol green method. The molar ratio of Bd from either source to underestimated albumin approximates 1.0, suggesting that one molecule of Bd would react equivalently to a molecule of albumin in the bromcresol purple method. This underestimation might falsely suggest hypoalbuminemia in patients with increased serum Bd. PMID- 1855301 TI - Improved fluorometric determination of malonaldehyde. AB - Lipoperoxidation is implicated in various pathological conditions. Malonaldehyde (MDA) is the most commonly used marker of this process. We propose simple modifications to Yagi's fluorometric assay for MDA determinations, to avoid long and tedious manipulations by eliminating the first precipitation and washing steps, analogous to HPLC methods, and to increase both the sensitivity and the specificity of the assay by measuring synchronous fluorescence. The proposed technique is easier, faster, and more sensitive than Yagi's method (Academic Press, 1982: Lipid peroxides in biology and medicine). The results obtained with the novel method correlate with those from the HPLC method described by Therasse and Lemonnier (J Chromatogr Biomed Appl 1987;413:237-41). PMID- 1855302 TI - Liquid-chromatographic determination of nicotine and cotinine in urine from passive smokers: comparison with gas chromatography with a nitrogen-specific detector. AB - We describe a simple, sensitive, and specific high-performance liquid chromatographic method with ultraviolet detection (256 nm) for the simultaneous analysis of nicotine and cotinine in urine of passive smokers. The analytes are extracted and purified from the complex and impure matrix in two stages; first, by liquid-liquid extraction and followed by solid-phase extraction (C2 column). We used a "DB" C8 5-microns-particle column (25 x 0.46 cm) and a mobile phase of phosphate-citrate buffer and acetonitrile (91:9 by vol) containing 5 mL of triethylamine and 600 mg of heptanesulfonate per liter, adjusted to pH 4.4, to separate the compounds. Two internal standards (2-phenylimidazole and N ethylnorcotinine) were used. The detection limit of the HPLC assay was less than 1 microgram/L for both analytes. The average interassay CV for nicotine was 7.6%, for cotinine 6.5%, in the concentration range 0-60 micrograms/L. The mean analytical recovery of nicotine with respect to the internal standard N ethylnorcotinine was 102% and that for cotinine was 99%; the mean absolute recoveries of the compounds were as follows: nicotine 85%, cotinine 87%, and N ethylnorcotinine 87%. To compare the HPLC assay results of 20 samples with the more-sensitive in-laboratory gas-chromatographic method with a nitrogen phosphorus detector, we used both N-ethylnornicotine and N-ethylnorcotinine as internal standards. The mean correlation coefficient for nicotine values between the two methods was 0.934; for cotinine, 0.987. PMID- 1855303 TI - Isocratic reversed-phase HPLC method to measure pyrimethamine extracted from plasma of infants treated for toxoplasmosis. AB - An isocratic HPLC method for measuring pyrimethamine extracted from infant plasma is reported. The method is an improvement over previously published methods by requiring lower volumes of plasma (100 microL) and having increased sensitivity to pyrimethamine at 210 nm. The procedure, which entails a basic organic extraction and subsequent HPLC chromatography of the reconstituted extract, can detect 1.4 ng and quantify 4.0 ng of pyrimethamine per 40-microL injection, with two analyses per 100-microL sample. Analytical recovery of pyrimethamine added to plasma at 10, 50, and 125 ng/100 microL averaged 80%, 92%, and 101%, respectively (n = 20). Within- and between-day CVs were less than 7%. Studies of various plasma samples from adults and infants (n = 15) revealed no interference from other plasma peaks with the analyte of interest. PMID- 1855304 TI - Aluminum phthalocyanine-streptavidin: new, sensitive fluorescent tracer for immunoassay. AB - A new fluorescent reagent based on aluminum phthalocyanine has been developed for general application to immunoassay. This highly sensitive fluorophore, Ultralite 680, may be covalently attached to a variety of biological entities for use as a tracer. We report the use of an Ultralite 680-streptavidin-digoxin conjugate as a tracer in a direct, competitive, heterogeneous, fluorescent immunoassay of digoxin. The assay is performed manually with 50 microL of serum and no sample pre-treatment. Primary anti-digoxin antibody is incubated with a serum sample containing digoxin and Ultralite 680-streptavidin-digoxin. Bound and free tracer are separated, and the bound fluorescence is released and quantified with a commercially available spectrofluorometer. Assay precision was good (CV = 7.05% at a digoxin concentration of 2.00 micrograms/L) and results by our method correlated well with those by a conventional RIA (r = 0.9650, n = 24). PMID- 1855305 TI - Citrulline concentrations in human plasma after arginine load. PMID- 1855306 TI - Quantification of free secretory component in saliva by enzyme immunoassay. PMID- 1855307 TI - Methadone in saliva. PMID- 1855308 TI - Time course of pH regulation in free thyroxin determinations in serum. PMID- 1855309 TI - Comparability of alkaline phosphatase isoenzyme methods. PMID- 1855310 TI - 4-Hydroxycyclohexanecarboxylic acid: a rare compound in urinary organic acid analysis. PMID- 1855311 TI - Urinary nitrite/nitrate ratio: marker for renal allograft rejection? PMID- 1855312 TI - Fluoxetine (Prozac) interference in CN column liquid-chromatographic assays of tricyclic antidepressants and metabolites. PMID- 1855313 TI - Biotin radioligand assay with polyethylene glycol as separation reagent. PMID- 1855314 TI - Interference of D-mannose, antiglycolytic agent, in glucose determinations. PMID- 1855315 TI - Agarose gel electrophoresis of alkaline phosphatase isoenzymes with wheat germ lectin and fluorogenic substrate. PMID- 1855316 TI - Wegener's granulomatosis with renal involvement: patient survival and correlations between initial renal function, renal histology, therapy and renal outcome. AB - Patient survival and renal outcome were followed in 25 patients with biopsy confirmed Wegener's granulomatosis and renal involvement. Fourteen out of 25 patients required dialysis on admission, 11/25 patients did not. All patients were treated with a novel protocol comprising methylprednisolone and cyclophosphamide. The median follow-up observation was 36 months (12-113 months). With the exception of 1 patient (who died from causes not related to Wegener's granulomatosis) all patients are alive. Among the patients initially requiring dialysis (n = 14) 4 are in terminal renal failure after 0, 7, 21 and 38 months respectively. In the nondialysis group (n = 11) only 1 patient subsequently required chronic dialysis 30 months after clinical admission. Renal failure was due to non-compliance with immunosuppressive therapy in at least 2 patients. Percentage of obsolescent glomeruli and the degree of tubulointerstitial lesions, but not active glomerular lesions (crescents, necroses) predicted renal outcome. The major cause of renal functional impairment was relapse of Wegener's granulomatosis usually within 2 years after clinical remission. Therefore prolonged treatment with cyclophosphamide for at least 2 years after clinical remission is recommended. Two patients with initially negative immunohistology had a second renal biopsy which revealed de novo appearance of mesangial IgA deposits. PMID- 1855317 TI - The effect of prostacyclin on intracranial pressure in patients with acute hepatic and renal failure. AB - Prostacyclin was administered on 20 occasions to 12 patients with fulminant hepatic failure complicated by acute renal failure prior to commencing dialysis at a dose of 5 ng/kg.min. Intracranial pressure was noted to increase during the infusion from a median of 12 mmHg (95% confidence limits 9-14) to 17 mmHg (12 25), p less than 0.01, at the same time the mean arterial blood pressure declined from 79 mmHg (65-82) to 64 (56-70), p less than 0.01, and the cerebral perfusion pressure from 62 mmHg (53-67) to 44 mmHg (41-55), p less than 0.01. The changes were greater for those patients who subsequently died from cerebral edema. Patients with fulminant hepatic and acute renal failure are at risk of dying from cerebral edema. The direct administration of prostacyclin, used for extracorporeal anticoagulation, may cause a further increase in intracranial pressure and reduce cerebral perfusion, thus resulting in patient morbidity and mortality. PMID- 1855318 TI - Effect of osmolar changes on plasma arginine vasopressin (PAVP) in dialysis patients. AB - The effect of changes in plasma osmolality and changes in plasma arginine vasopressin (PAVP) were analyzed in 10 stable chronic hemodialysis patients utilizing four protocols. During regular hemodialysis opposing influences on PAVP (decrease in blood pressure and intravascular volume and increase in serum calcium) resulted in no significant change in PAVP (by analysis of variance). In the second protocol low dialysate calcium (2.5 meq/l) isovolemic hemodialysis was used. PAVP and serum osmolality levels declined from 2.0 +/- 0.4 to 1.4 +/- 0.2 microU/ml (p less than 0.05), and 285 +/- 2.5 mOsm/l to 275 +/- 3.2 mOsm/l respectively. Removal of PAVP by hemodialysis did not occur as evidenced by no difference in arterial-venous PAVP levels and no "rebound" of PAVP for three hours after completion of dialysis (second protocol). Isovolemic low calcium high dialysate sodium (145 meq/l) hemodialysis was utilized in the third protocol. Serum osmolality and PAVP did not change. Addition of a very high dialysate sodium (155 meq/l) to isovolemic low calcium hemodialysis resulted in an increase in plasma sodium, osmolality and AVP (139.7 +/- 0.62 to 144 +/- 0.67 meq/l, 294 +/- 2.79 to 304.3 +/- 2.4 mOsm/l and 1.8 +/- 0.3 to 2.7 +/- 0.5 microU/ml (p less than 0.05 for each) respectively. In conclusion, PAVP responds to changes in plasma osmolality in chronic hemodialysis patients. PMID- 1855319 TI - Influence of erythropoietin treatment on urea kinetic parameters in hemodialysis patients. AB - Urea kinetic parameters were studied by means of dialysate collection in 8 stable hemodialysis patients before and after treatment with recombinant human erythropoietin (r-HuEPO), in order to investigate the impact of a rising hematocrit (Ht) on dialyzer performance and nutritional status. After 6 months, the average in vivo dialyzer urea clearance had fallen from 152 to 132 ml/min and consequently Kt/V values had become undesirably low in most of the patients in whom the relatively short dialysis regimens had been kept unchanged. There was also a significant decrease of protein intake. As a result of both changes there was only a moderate increase of predialysis mean blood urea concentration. These findings indicate that after correction of anemia by r-HuEPO dialyzer performance decreased. The concomitant decrease of protein intake seems to contrast to the improved general physical condition and appetite as indicated in the questionnaires. Although body weight remained the same, there might have been a tendency to avoid protein consumption with maintained total calory intake as a result of slight underdialysis. Therefore, in individual cases dialysis prescriptions may need reconsideration when Ht levels rise after r-HuEPO administration, especially in short dialysis regimens. PMID- 1855320 TI - Acute encephalopathy due to thiamine deficiency (Wernicke's encephalopathy) in a chronic hemodialyzed patient: a case report. AB - We report the case of a patient with terminal renal disease on chronic hemodialysis who developed acute thiamine deficiency as confirmed by erythrocyte transketolase determinations. The patient presented with a confusional state and severe memory disturbances, but other classical features of Wernicke's encephalopathy were absent. Almost all central nervous system symptoms rapidly disappeared after thiamine therapy. Therefore the possibility of thiamine deficiency must be considered in patients on chronic dialysis who present with central nervous system disturbances, even if all of the classical features of Wernicke's encephalopathy are not present. PMID- 1855321 TI - Comment on "Use of aminohydroxypropylidene bisphosphonate (AHPrBP, "APD") for the treatment of hypercalcemia in patients with renal impairment" by Yap et al. PMID- 1855322 TI - Prevalence of HLA-B27 antigens in patients with dialysis-related beta 2-M amyloidosis. PMID- 1855323 TI - Comment on "Portions of basement membrane with decreased negative charge in various glomerulonephritis". PMID- 1855324 TI - The treatment of mesangial IgA nephropathy with cyclophosphamide, dipyridamole and warfarin. PMID- 1855325 TI - Comment on "Idiopathic acute interstitial nephritis associated with anterior uveitis in adults" by P. Cacoub et al. PMID- 1855326 TI - Progression of a naproxen and amoxicillin induced acute interstitial nephritis with nephrotic syndrome: case report. AB - This article reports an unusual case of acute interstitial nephritis associated with nephrotic syndrome which appeared after oral intake of naproxen and amoxicillin and led to end-stage renal failure. In the light of recent literature on this clinical entity, the authors formulate hypotheses accounting for this outcome. PMID- 1855327 TI - Vaccination for prevention of CAPD associated staphylococcal infection: results of a prospective multicentre clinical trial. AB - 124 stable CAPD patients from 8 Australian and 3 New Zealand centers were randomly assigned in a blinded fashion to one of two groups to study the effect of vaccination using commercial preparations consisting of a combined staphylococcus toxoid and whole killed staphylococci (SB) or normal saline solution (SS) on the incidence of peritonitis and exit site infection and S. aureus nasal carriage over a 12-month prospective period. In addition, levels of IgG, IgA, IgM, C3 and C4 were monitored during the trial period in serum and dialysate; serum levels of anti-alpha hemolysin and dialysate levels of fibronectin and specific antistaphylococcal antibodies were also measured. Over the period, treatment with SB or SS did not affect the incidence of peritonitis, catheter-related infection or S. aureus nasal carriage. However, vaccination with SB elicited a significant increase in the level of serum anti-alpha hemolysin throughout the 12 month duration of the study, although the level of increase was unrelated to the subsequent rate of peritonitis. Vaccination with SB but not SS elicited a significant increase in the dialysate level of specific antibodies against S. aureus. Serum levels of IgG, IgA, IgM, complement C3 and C4 were within the normal range in the CAPD patients studied and remained unaffected by vaccination with SB. In addition, dialysate levels of IgG, IgA, IgM, complement C3 and C4 were 50-100 times lower than corresponding serum levels and remained unaffected by vaccination. In summary, immunisation with an anti-staphylococcal agent was not successful in reducing peritonitis or exit site infection in CAPD patients. PMID- 1855328 TI - Correction of anemia in patients on continuous ambulatory peritoneal dialysis with subcutaneous recombinant erythropoietin twice a week: a long-term study. AB - Subcutaneous recombinant human erythropoietin (rHuEPO) was given for 12 months twice weekly to 10 patients on continuous ambulatory peritoneal dialysis (CAPD) with anemia (hemoglobin less than 9.0 mg/dl). All patients responded to a median weekly dose of between 37.5 to 100 (mean 55 to 105) units/kg and reached a target hemoglobin of 10-12 mg/dl in a mean of 11.7 weeks (range 5-24). Serum iron, iron saturation and ferritin were significantly lower and serum potassium was significantly higher than the pre-treatment level from 1 month onwards. Five patients without pre-treatment iron overload required oral iron supplement and 3 required oral potassium-binding resin. No significant change in other serum biochemical parameters was observed. Blood pressure remained stable during the treatment period but additional or increased dosage of antihypertensive drugs was required in 5 patients. Peritoneal small solute clearance and ultrafiltration and residual renal clearance did not change significantly after correction of anemia. The incidence of peritonitis and exit site infection was similarly unaffected. One patient developed a severe headache which was not associated with hypertension and responded to withdrawal of rHuEPO treatment. Most of the remaining patients showed improvement in subjective well-being. It was concluded that the subcutaneous route twice a week is a safe, convenient and cost-effective way to administer rHuEPO to patients on CAPD. PMID- 1855329 TI - Removal of trace metals by continuous ambulatory peritoneal dialysis after desferrioxamine B chelation therapy. AB - We studied the removal of aluminum (Al), iron (Fe), copper (Cu), lead (Pb) and zinc (Zn) with continuous ambulatory peritoneal dialysis, before and after desferrioxamine B (DFO) administration (2 g intravenously) in two patients with chronic renal failure and Al-related osteopathy. Both patients had 4 peritoneal dialysis exchanges (2 liters each) per day. Blood concentrations of Al increased 413% (patient A) and 190% (patient B) after DFO. Patient B had a 15% increase in Fe; other metals remained unchanged. Dialysate efflux Al concentrations had peak post-DFO increments of 761% and 840% in patients 1 and 2, respectively. Peak post DFO increments in Fe dialysate concentration were 342% and 89.5% in the respective patients. Dialysate/plasma (D/P) concentration ratios of Al increased from pre-DFO levels (mean +/- SEM) of 0.370 +/- 0.048 to 0.523 +/- 0.061 after DFO; similarly, Fe D/P ratios increased from 0.259 +/- 0.053 to 0.446 +/- 0.075 with DFO therapy. These results indicate an increase in the ultrafiltrable proportion of Al and Fe in plasma after DFO administration. During 3 days after DFO, patient 1 had a total removal of Al and Fe of 2.9 mg and 4.9 mg, respectively. Metal removal in patient 2 was 7.6 mg of Al and 2.7 mg of Fe. Peritoneal extraction of other trace metals was minor. PMID- 1855330 TI - Hypersensitivity reactions during hemodialysis related to the use of acetate dialysate. A case report. AB - A patient developed a hypersensitivity reaction two weeks after being put on hemodialysis with acetate dialysate. The reactions appeared exclusively during hemodialysis and were relieved immediately after its termination. These allergic manifestations disappeared with substitution of bicarbonate for acetate dialysate and reappeared upon rechallenge with acetate dialysate. The rest of the dialysis materials were excluded as possible causes of allergy by scheduled dialysis sessions with varying materials. Acetate dialysate is implicated as the cause of allergy reaction in this case. PMID- 1855331 TI - Shoulder ultrasound in dialysis related amyloidosis. AB - Ultrasonographic changes around the shoulder joint were compared in ten symptomatic patients with dialysis related amyloid (DRA) and seventeen patients without symptoms. All patients had been on long-term (greater than 7 years) hemodialysis (HD). Three control groups were used: 8 predialysis patients, 10 continuous ambulatory peritoneal dialysis (CAPD) and 9 HD patients who had been on dialysis for less than two years. Dry bodyweight, sex, handedness, length of hemodialysis and fistula side were not significantly different between the study groups. Proven amyloid patients were significantly older than other groups (p less than 0.001). Parameters assessed included cross-sectional area of long head of biceps tendon (LHB), diameter of supraspinatus tendon (SS), and general features (bursae, deposits) around the joint. Results demonstrated significant differences in all parameters in patients with symptomatic amyloid compared with other long-term patients: [SS: 7.4 mm +/- 0.7, mean +/- SEM, vs 5.1 +/- 0.2 (right, R), p = 0.001; 6.7 +/- 0.7 vs 4.9 +/- 0.2 (left, L), p = 0.01. LHB: 140.0 mm2 +/- 11.1 vs 79.6 +/- 5.1 (R), p less than 0.001; 114.5 +/- 10.5 vs 80.8 +/- 5.4 (L), p = 0.004. Bursae: 5 vs 1 (patients), p = 0.006]. Compared with controls changes in the amyloid group were less marked though in most cases still significant. There was no significant difference between control groups nor between controls and asymptomatic long-term HD patients in any parameter. We conclude that shoulder ultrasound may have a role in identifying patients with dialysis related amyloid. Serial measurements may also help to elucidate the pathogenesis of the tendon changes. PMID- 1855332 TI - Evaluating the recirculation in hemodialysis without peripheral venipuncture. PMID- 1855333 TI - Ultrastructure in human implantation: transmission and scanning electron microscopy. PMID- 1855334 TI - Factors of importance for implantation. PMID- 1855335 TI - Immunocytochemical localization of oestradiol and progesterone receptors in human endometrium: a tool to assess endometrial maturation. AB - Uterine oestrogen (ER) and progesterone (PR) receptors are subject to fine hormonal control by oestradiol and progesterone. In order to assess the role of ER and PR measurement in the evaluation of endometrial maturation, both receptors were studied by immunocytochemical techniques using monoclonal antibodies during the menstrual cycle, and in women with inactive ovaries treated by different regimens of hormonal substitution with oestradiol and progesterone. During the normal menstrual cycle, the concentrations and distribution of ER and PR changed markedly. During the mid follicular period (days 7-8), a small proportion of stromal and glandular cells stained positively for PR while staining for ER was more intense and more frequent. During the late follicular phase and early luteal period (days 9-19), the staining for PR increased markedly in glandular cells. During the mid and late luteal phase (days 21-27), ER and PR staining disappeared in glandular cells. Thus, while oestradiol increases the staining for ER and PR in both glands and stroma, progesterone decreases ER and PR staining in the glands in a dramatic fashion. These variations, especially the disappearance of PR under the effect of progesterone, are potentially useful for studying the cumulative effect of progesterone on endometrial maturation. This was confirmed in anovulatory women, where a late luteal phase aspect was observed, i.e. the absence of a reduction in ER and PR in glandular cells. In women with ovarian failure, the disappearance of ER and PR in glandular cells is correlated with the duration of progesterone therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855336 TI - Role of embryonic factors in implantation: recent developments. AB - The embryonic factors influencing implantation have been studied extensively in laboratory and domestic animals, but not in primates, including humans. Species differences make extrapolation inadvisable. Embryonic factors affecting implantation include intrinsic features of the embryo, such as its genetic constitution, morphology and hatching. Abnormal genetic constitutions or unsuccessful transitions from maternal to embryonic transcription could account for many failures of early embryonic growth and implantation. Morphology per se does not greatly influence implantation, except when it reflects an abnormal genetic constitution, e.g. in severe fragmentation, although subtle effects may be detected as experimental techniques are refined. The initiation of differentiation and intraembryonic communication between cells and cell types has been studied in animal embryos. Signals must be exchanged between the embryo and the mother to ensure satisfactory implantation. These could include platelet activating factor, prostaglandins, histamine related factors, steroids, proteins, metabolic products and immune-active factors. No one factor seems to be totally responsible for alerting the mother to the presence of an embryo, and a concerted action of these and other agents is probably responsible. The process of implantation itself is poorly understood because of a lack of adequate experimental models. The expression of complementary proteins and the role of specific enzymes and markers of endometrial and embryonic competence are factors well worthy of further study. Knowledge about human implantation is increasing because of recent developments in assisted reproductive technology, and concepts arising from many years of research in animals should find clinical applications in understanding and controlling human reproduction. PMID- 1855337 TI - Function of blood vessels relative to implantation. PMID- 1855338 TI - A consideration of the factors which influence and control the viability and developmental potential of the preimplantation embryo. AB - The advent of the new reproductive technologies (including in vitro fertilization) has led to a revolution in the treatment of infertility. It has not yet led to a marked improvement in our understanding of the control of development and of viability of the early embryo. It is the poor viability of embryos, with consequent implantation failure, which is the major limiting factor to successful outcomes. While much of the research in this area has concentrated on strategies of ovulation induction, experimental models have shown that the major cause of reduced embryo viability is due to the actual process of fertilization in vitro and subsequent culture of the preembryo in synthetic culture medium. It is likely that this is due to the absence of critical nutrients or trophic factors of maternal origin and work with co-culture of embryos with somatic cells suggests improved viability can be achieved. Such co culture is not an option for routine clinical use, however. It is essential therefore to understand by detailed study of the physiology of embryonic development their requirements for optimal development. The empirical approach of comparing different formulations of culture media is unlikely to be successful because of the vast range of parameters to be tested and the large number of pregnancies required to demonstrate a significant improvement in outcome. The strategy that is most likely to be successful in the future, therefore, is the use of appropriate experimental models, such as the developing rodent embryo, to understand the essential physiological changes in the embryo during its development, the control processes in place, and the effect of the embryo's environment on the processes. This will allow the rational design of culture media which can then be rigorously tested for improved outcome. An example of successful application of this approach is the discovery of embryo-derived platelet activating factor (PAF). The production of embryo-derived PAF was first described and validated in the rodent. In the same species it was shown to have an essential role in pregnancy and to act as an autocrine mediator of embryo viability. This fundamental observation in rodents was then confirmed in humans, and recent work has shown that supplementation of culture human embryo media with PAF results in a dramatic increase in their developmental and pregnancy potential. This example should be the first of many such improvements based on a more fundamental understanding of the embryo's developmental requirements. PMID- 1855339 TI - Frequency of implantation and early pregnancy loss in natural cycles. PMID- 1855340 TI - Morphological and histochemical factors related to implantation. PMID- 1855341 TI - Implantation failure: clinical aspects. PMID- 1855342 TI - Macrophages and migratory cells in endometrium relevant to implantation. AB - The implantation of an appropriately developed embryo into a suitably conditioned uterine lining depends on the synchronous maturation of the preimplantation embryo and uterine lining. The pre- and postimplantation embryo also requires protection from immunocompetent maternal immune effectors. Preimplantation embryo development is affected by genotype, intercellular communication and autocrine growth factors (polyamines, TGF-alpha, TGF-beta 1, PAF). Factors of maternal origin may also enhance embryo development (EGF, TGF-alpha, TGF-beta 1, IGF, polyamines). The preimplantation embryo signals its presence to the mother by release of factor(s) such as IFN-alpha-II and a PAF-like factor. PAF may induce EPF in the mother and enhances vascular permeability at the implantation site. Uterine or peritoneal leukocytosis may inhibit development via toxic effects of lymphokines/monokines (IL-2, IL-1?, IFN-gamma, TNF-alpha). Immunoprotection of the preimplantation embryo is conferred by embryo derived maternal factors (EPF, T-cell suppressor factors). The uterus is receptive during a limited period of time (implantation window) and the substrate adhesion molecules produced by uterine and embryonic trophectoderm cells are crucial for the initial stages of implantation. At implantation, trophoblast expression of MHC and non-MHC antigens is shut off and both immunocompetent maternal cells (macrophages, dendritic cells, granulocytes, IELs, immunocytes) and lymphatics become sparse at implantation sites. Peri-implantation cytokines of maternal origin, such as CSF 1, GM-CSF and IGF-1 binding protein, are probably important for trophoblast growth and development. Immuno-protection of the embryo at this stage may be mediated by embryo derived factors that inactivate macrophages and by a population of large, hormone dependent Lyt 2+ (CD8+) suppressor cells. It is possible that these CD8+ cells respond to progesterone and secrete molecules that inactivate natural effector (NK-type) cells against trophoblast. Prostaglandins (PGE2) may play a brief role in immunosuppression at the time of implantation but its role is probably more important with respect to the decidual response. Defects in the pre- and peri-implantation stages of pregnancy may lead to delayed failure in the form of clinical miscarriage. PMID- 1855343 TI - Human endometrial protein secretion relative to implantation. PMID- 1855344 TI - The role of prostaglandins in implantation. PMID- 1855345 TI - Endometrial prolactin and implantation. AB - The role of prolactin in human implantation and human endometrial function is still unclear. Synthesis of prolactin from human endometrium and decidua was first demonstrated in 1977. Prolactin mRNA isolation from term decidua subsequently confirmed expression of the prolactin gene in human endometrium. More recently, a glycosylated form of prolactin has been isolated from both the human pituitary and human endometrium. It appears that predominately glycosylated prolactin is secreted in the late luteal phase of the menstrual cycle, with increasingly greater amounts of non-glycosylated prolactin secreted as pregnancy advances. The biological significance and regulation of prolactin glycosylation is uncertain, although glycosylated ovine prolactin has only 20-33% of the lactogenic activity of ovine prolactin. Pituitary lactotropes, of ectodermal origin, produce pituitary prolactin and are regulated by dopamine, oestradiol and thyrotropin releasing hormone. Decidual cells, of mesodermal origin, are not influenced by these pituitary secretogogues. Progesterone and calcium both appear to stimulate pituitary and decidual prolactin secretion, while arachidonic acid seems to inhibit decidual prolactin release. More recently, insulin like growth factor-1, a polypeptide growth factor implicated in the oestrogen promoted growth reproductive tissues, has been found in high concentration in the pig uterus and has been shown to stimulate the synthesis and secretion of prolactin from human decidua. Prolactin receptors have not been reported on endothelium of blood vessels and no clear evidence exists that endometrial prolactin may modulate the secretion of endothelin, endothelium derived relaxing factor or other potentially important substances controlling menstruation. Prolactin does appear necessary for the normal production of macrophage activating factors, including interferon, and may have a local immunomodulatory role upon human implantation for this reason. Human alpha 2-interferon has sequence homology to ovine trophoblast protein-1 and is found in high concentration in human pregnancy and fetal tissues. There is some evidence that interferon may reduce human endometrial prolactin secretion, but whether endometrial or decidual prolactin is critical to human implantation awaits further study. PMID- 1855346 TI - Report of a survey of some aspects of editorial board peer review at Clinical Pharmacology & Therapeutics. PMID- 1855348 TI - No causal relationship between transdermal scopolamine and seizures: methodologic lessons for pharmacoepidemiology. AB - Because of case reports suggesting that use of transdermal scopolamine might be associated with the subsequent development of seizures, a retrospective cohort study was performed with computerized Medicaid claims data. Patients receiving transdermal scopolamine were compared with patients receiving diphenhydramine, meclizine, prochlorperazine, and promethazine. A four-fold increased risk of seizures after transdermal scopolamine use was observed in the claims data. However, this was not supported by the primary medical records. All patients who had seizures after using transdermal scopolamine either had seizures before receiving the drug as well or did not really suffer from seizures. The original finding appeared to be the result of the use of transdermal scopolamine for "dizziness, rule out seizures"; the ICD-9-CM coding system does not include "rule out" diagnoses. Thus these data do not confirm the existence of an association between seizures and the use of transdermal scopolamine. In addition, this study demonstrates the usefulness of pharmacoepidemiology studies in documenting drug safety and the importance of obtaining primary medical records when performing pharmacoepidemiologic studies with claims data. PMID- 1855347 TI - Increased carbamazepine plasma concentrations after fluoxetine coadministration. AB - The interaction between fluoxetine and carbamazepine was investigated in six normal, healthy male volunteers (aged 23 to 40 years). Subjects were given carbamazepine, 400 mg every morning, for 3 weeks. Venous carbamazepine blood samples were obtained at baseline and 1, 2, 4, 6, 8, 10, 12, and 24 hours after the morning dose. Fluoxetine, 20 mg every morning, was then coadministered with carbamazepine for 7 days. Venous carbamazepine blood samples were again obtained as described. Carbamazepine and carbamazepine-10,11-epoxide (CBZE) were assayed by HPLC. Addition of fluoxetine resulted in a significant increase in the area under the concentration-time curve of carbamazepine (105.93 +/- 18.05 micrograms/ml.hr versus 134.97 +/- 12.15 micrograms/ml.hr; t = 3.284; df = 5; p = 0.022) and CBZE (11.6 +/- 1.93 micrograms/ml.hr versus 15.2 +/- 2.4 micrograms/ml.hr; t = 2.805; df = 5; p = 0.038). Both oral and intrinsic clearance of carbamazepine was decreased significantly on fluoxetine addition (3.87 +/- 0.68 L/hr versus 2.98 +/- 0.26 L/hr; t = 3.025; df = 5; p = 0.029 and 17.90 +/- 4.9 L/hr versus 11.92 +/- 1.4 L/hr; t = 3.037; df = 5; p = 0.029, respectively). No significant changes were determined for fraction of absorbed dose, volume of distribution, absorption rate constant, and elimination rate constant. These findings suggest that fluoxetine can inhibit the metabolism of carbamazepine. Careful monitoring of patients is recommended when these two drugs are coadministered. PMID- 1855349 TI - The influence of dosage time of midazolam on its pharmacokinetics and effects in humans. AB - The influence of dosage time of midazolam on its pharmacokinetics and effects on the central nervous system were investigated in six healthy volunteers, with pharmacokinetic-pharmacodynamic modeling. Each volunteer received single oral doses of 15 mg midazolam on four separate occasions: 8 AM, 2 PM, 8 PM, and 2 AM. An almost significant circadian variation was found in elimination half-life, shortest at 2 PM (1.26 +/- 0.47 hours, mean +/- SD) and longest at 2 AM (1.57 +/- 0.44 hours) (p = 0.05). Drug effects measured were alpha activity of the electroencepalograph and P100 latency of the visual-evoked response. The maximum drug effect (Emax) model described the concentration-effect relationship, extended with either a threshold drug concentration or a sigmoidicity parameter. A significant circadian variation was found in baseline alpha activity: highest at 8 AM (109% +/- 19% of the 24-hour mean) and lowest at 2 AM (80% +/- 12%). For alpha activity the drug concentration at half-maximum effect of both threshold Emax model and sigmoid Emax model showed lower values at 8 AM and 2 AM and higher values at 2 PM and 8 PM. However, these differences were either not significant (p = 0.10, threshold model) or on the verge of statistical significance (p = 0.05, sigmoid model). No circadian variation was found in the parameters describing the effect on the visual-evoked response. We conclude that the sensitivity of the central nervous system to midazolam, as reflected in alpha activity, possibly shows a circadian variation. PMID- 1855350 TI - Gentamicin population pharmacokinetic models for low birth weight infants using a new nonparametric method. AB - Availability of personal computer programs for control of drug regimens has stimulated interest in modeling population pharmacokinetics. In this study, we found parameter values for gentamicin in two infant populations with low birth weights. The models were developed by use of a parametric (i.e., standard two stage algorithm) and with a new nonparametric expected maximum algorithm. Data for the two populations (i.e., infants less than or equal to 31 weeks' and greater than 31 but less than or equal to 34 weeks' gestational age) were obtained from infants admitted to the University of Texas Medical Branch intensive care nursery between August 1, 1988, and July 31, 1989. The new nonparametric method was demonstrated to be not only the equal of the standard two-stage method for population modeling but better, especially in use of sparse data sets (e.g., single serum levels). It also obviates the need for selecting proper starting conditions for the least-squares fitting procedure used in the standard two-stage method. PMID- 1855351 TI - Doxapram metabolism in human fetal hepatic organ culture. AB - The biotransformation of doxapram, a respiratory stimulant was studied with use of explants from human fetal livers (n = 15 fetuses) obtained from therapeutic abortions (gestational age, 10 to 20 weeks). Explants were cultured in Leibowitz medium and the media from cultured samples were collected before and at 3, 6, 12, and 24 hours after incubation with 2.5, 5.0, and 10 micrograms/ml doxapram. The concentrations of doxapram and its metabolites (AHR 0914, an analog of doxapram, AHR 5955 or ketodoxapram, and AHR 5904) were measured by high pressure liquid chromatography. Explant histopathology and alkaline phosphatase activity showed no direct toxic effects of the drug on liver tissue. The fastest rate of doxapram metabolism occurred during the first 3 hours of incubation (198 +/- 73.3, 438 +/- 63.3, and 538 +/- 62 ng/mg/hr liver protein at doxapram concentrations of 2.5, 5.0, and 10.0 micrograms/ml, respectively). At 3 hours of incubation, the amount of doxapram metabolized (nanogram per milligram of liver protein) was significantly higher (p less than 0.01) at doxapram concentrations of 10.0 (1616 +/- 186) and 5.0 microgram/ml (1315 +/- 190) than at 2.5 micrograms/ml (594 +/- 220). The oxidative pathway producing keto-doxapram, or AHR 5955 and AHR 5904, is more active than the de-ethylation producing the analog of doxapram AHR 0914. Data indicate substantial metabolism of doxapram by the human fetal lives. PMID- 1855352 TI - The intellectual health of clinical drug evaluation. PMID- 1855353 TI - Netilmicin in the neonate: population pharmacokinetic analysis and dosing recommendations. AB - Netilmicin pharmacokinetics were studied in neonates of 27 to 42 weeks' gestational age and 0.8 to 5.0 kg body weight in their first 2 weeks of life by the population pharmacokinetic approach. The data were best described by a two compartment model. Clearance depends on body weight, gestational age, and postnatal age. Volume of distribution of the central and peripheral compartments was also related to body weight. Including these patient characteristics in the population pharmacokinetic regression model resulted in a marked reduction of the unexplained interindividual variability. This enabled us to derive dosage recommendations that result in peak and average concentrations within the desired range for 95% of the neonates with gestational age above 31 weeks, thus avoiding the need for individual drug-level monitoring in a well-defined large group of patients. Only for infants with gestational age less than 31 weeks who are less than 6 days old is individual dose adjustment based on serum concentration measurements required. PMID- 1855354 TI - Tolerance to nicotinic acid flushing. AB - The mechanism of tolerance to nicotinic acid flushing was determined in subjects during a 5-day course of treatment. Objective measures of skin blood flow were used to confirm the development of tolerance. Plasma levels of nicotinic acid showed marked intraindividual variability but were not decreased with the development of tolerance. However plasma levels of 9-alpha 11-beta prostaglandin F2, a stable metabolite of prostaglandin D2, became undetectable in most subjects with the development of tolerance. Thus tolerance is not associated with decreased levels of nicotinic acid or development of tolerance to the prostaglandin mediator, but with decreased levels of the mediator. PMID- 1855355 TI - Local anesthesia blocks the antiemetic action of P6 acupuncture. AB - The incidence of postoperative illness was monitored for 6 hours in 74 women premedicated with nalbuphine, 10 mg, and undergoing short gynecologic operations of similar duration under methohexitalnitrous oxide-oxygen anesthesia. Each patient received P6 acupuncture for 5 minutes at the time of administration of premedication. In random order the site of the acupuncture had been previously infiltrated with normal saline solution in half of the patients and 1% lidocaine in the remaining patients. Postoperative emetic sequelae occurred significantly more often in those who received lidocaine compared with the group that received saline solution. This demonstrates the ability of a local anesthetic administered at the point of stimulation to block the antiemetic action of P6 acupuncture in a manner similar to that shown by others for analgesia. PMID- 1855356 TI - Cocaine reduction in unmotivated crack users using carbamazepine versus placebo in a short-term, double-blind crossover design. AB - On the basis of cocaine-caused kindling in animals and the usefulness of carbamazepine in treating kindling-type seizures, carbamazepine has been tried in clinical settings with cocaine-dependent individuals. This report presents findings of a 20-day, double-blind, placebo-controlled crossover study in 32 nontreatment-motivated, paid, chronic crack cocaine users. Carbamazepine significantly lowered the mean number of positive urine specimens compared with placebo. Of clinical importance, serum carbamazepine levels of 4 micrograms/ml (17 mumol/L) or more were associated with greater improvement. A consistent, clinically important trend linked therapeutic levels with improvement for all subjective and objective outcome variables. Comparison of daily acknowledged cocaine use or professed cocaine abstinence, with cocaine use indicated by daily urinalysis in these chronic cocaine users, has suggested the possibility of cocaine saturation as an important methodologic limitation inherent in outpatient studies of cocaine use in humans. PMID- 1855358 TI - Measurement of properties and function of skin. AB - Dermatologists and skin biologists have traditionally approached the diagnosis of skin diseases by either a very gross measurement of its physical state, i.e. a skin pinch, or at the other extreme by being concerned with the cellular and sub cellular organisation of the skin. Recently, using methods often borrowed from materials science, techniques have been developed and used to aid the investigation of the changes that occur with disease and ageing, for example. A review of these methods developed to study the structure and function of skin by the physical scientists working in close collaboration with dermatologists, pathologists and skin biologists is presented. PMID- 1855357 TI - Enalapril effects on alcohol intake and other consummatory behaviors in alcoholics. AB - Animal studies suggest that angiotensin-converting enzyme inhibitors decrease alcohol intake. In a double-blind crossover study 42 normotensive alcoholics (36 men and six women) aged 24 to 65 years, consuming 8.2 +/- 2.3 (mean +/- SD) standard alcoholic drinks per day, were randomized to enalapril, 10 mg/day (n = 20) or 20 mg/day (n = 22), and placebo for 4 weeks. They monitored their daily alcohol intake and attended biweekly assessments, but no other treatment or advice was given. Compliance and alcohol intake were verified objectively. Mean daily alcoholic drinks were not significantly different during 10 mg/day enalapril (mean +/- SEM, 7.5 +/- 0.5), and its placebo (7.2 +/- 0.5), but both decreased from baseline (8.1 +/- 0.5; both p less than 0.05). Similarly, mean daily drinks during 20 mg/day enalapril (6.8 +/- 0.6) and its placebo (7.2 +/- 0.4) was not significantly different, but both were lower than baseline (8.3 +/- 0.5; both p less than 0.01). Fourteen (64%) of the patients taking 20 mg/day enalapril decreased alcohol intake from placebo by an average of 21% (range, 1.6% to 78.3%). Self-ratings of interest, desire, craving, and liking for alcohol also decreased from baseline during enalapril and placebo treatments, but the effects of both were similar. Plasma renin activity increased, compared with placebo, after 10 mg/day enalapril (from 0.3 +/- 0.2 [mean +/- SD] to 1.9 +/- 1.5 ng/L/sec) and after 20 mg/day enalapril (from 0.4 +/- 0.3 to 2.8 +/- 4.0 ng/L/sec) (both p less than 0.05). Blood pressure decreased within a normotensive range, compared with placebo, with 10 mg/day enalapril (by 6.0 and 8.5 mm Hg systolic and diastolic blood pressures) and 20 mg/day enalapril (by 7.7 and 5.0 mm Hg, respectively). Side effects were few and mild. No patient characteristic or drug effect correlated with changes in alcohol intake. There were no significant variations in nonalcoholic beverages, cigarette smoking, or body weight. These results indicate that enalapril does not alter alcohol intake in normotensive alcoholics with normal plasma renin activity. Studies with higher doses of enalapril in humans may be limited by increased frequency and severity of side effects. PMID- 1855359 TI - Acoustic reflectometry for airway measurement. Principles, limitations and previous work. AB - Acoustic pulse reflectometry is a relatively recent technique which allows the non-invasive measurement of human airways. The technique consists of guiding an acoustic impulse through the subject's mouth and into the airway. Suitable analysis of the resulting reflection (the 'echo') allows a reconstruction of the area-distance function. The non-invasive nature of the technique offers significant advantages over the established methods of x-ray cephalometry and CT scanning, and makes it very attractive for the investigation of ENT problems and sleep apnoea, and in the anaesthetic management of patients. This paper describes the theory and limitations of acoustic reflectometry, discusses previous work, and suggests some modifications: it is currently being implemented clinically. PMID- 1855360 TI - Burn wound evaporation--measurement of body fluid loss by probe evaporimeter and weight change. AB - A knowledge of the rate of fluid loss from the body is a useful aid in planning treatment of patients with severe burns. Different methods for obtaining this data have been investigated. Evaporation rates recorded from a probe evaporimeter have been compared with gravimetric measurements. The evaporimeter underestimated evaporation, especially at high levels, but could be calibrated against known evaporation rates. Estimates of whole-body fluid loss have been made from calibrated evaporimeter data and results compared with measurements of fluid loss by weight change for three patients. Problems with assessing whole-body evaporation rates in the clinical environment are highlighted. Weight change gives a more accurate assessment of total body fluid loss, but considerable effort is necessary to record all relevant information. Probe evaporimeter measurements are simple to perform and allow local evaporation rates to be estimated, but results should be treated with caution. Evaporation rates from wounds of 17 patients with severe burns have been evaluated in terms of surface diffusion resistances. The diffusion resistances of some burn wounds increased with time, but many did not change significantly during the first ten days after injury, and there was considerable variation with burn type and severity. PMID- 1855361 TI - The resolution of transcranial Doppler scanning: a method for in vitro evaluation. AB - The circle of Willis may be examined using low frequency pulsed Doppler ultrasound transmitted through the thin squamous temporal bone or 'acoustic windows' of the skull. The thickness and shape of these windows affect the characteristics of the ultrasound beam and partly determine the spatial resolution of transcranial Doppler scanning. We have studied the effects of temporal bone on the ultrasound beam and sample volume characteristics of the EME Transcan 2 MHz transducer using a stepper motor, computer-controlled ultrasound plotting system. The lateral and axial spatial dimensions of the sample volume, and a direct estimate of the lateral resolution of the system, were determined at various depths of interest using Doppler targets. The results in this initial study of a small number of specimens indicates a decrease in sample width, and hence an increase in lateral resolution, presumably due to the lensing effect of the skull cusping. The estimated lateral resolution of the system is of the order of 4 mm. PMID- 1855362 TI - Method for evaluation of the urethral closure mechanism in women during standardised changes of cross-sectional area. AB - A method for evaluation of the closure mechanism in the female urethra during forced opening has been developed and tested. The cross-sectional area (CA) of the tube and the intraluminal pressure were measured simultaneously by a specially designed balloon catheter. The method enables induction of standardised changes of CA at different rates. Applied in the female urethra the induction results in a distinct pressure response which increases with increasing rate of change of CA as well as size of the induction. The inflation of the balloon simulates a forced opening of the urethra and hence leakage. Obviously, urinary incontinence takes place at forced opening of the urethra. Accordingly, this novel method can give important information on the pathophysiology of stress urinary incontinence in particular and the physiology of sphincter functions in general. PMID- 1855363 TI - Closed loop blood pressure control for cerebral perfusion studies. AB - A method is presented which maintains mean arterial blood pressure at predetermined values during cerebrovascular occlusion studies in a rat model. The system consists of a pressure measurement apparatus, a pump capable of infusing and withdrawing fluids, and a personal computer to control the infusion and withdrawal rate. An evaluation of the system is presented, and potential advantages and difficulties are discussed. PMID- 1855364 TI - A Doppler signal simulator. AB - A simulated Doppler signal generator has been developed using computer controlled band-pass filtering of a broad-band noise source. The instrument may be used to generate simulated Doppler signals of known spectral characteristics in order to test Doppler signal analysers. PMID- 1855365 TI - The retrieval, storage, numerical and graphical trending of data from an Ohmeda 3700e pulse oximeter by personal computer. AB - A suite of computer programs are described to facilitate the transfer, disc storage, graphical trending and statistical analysis of data from an Ohmeda 3700e pulse oximeter. The programs are written in GWBASIC and designed to operate on a low cost IBM PC or compatible personal computer. The programs have been proved to be clinically useful in determining response to therapy as discerned from the long-term monitoring of arterial oxygen saturation. The computerised system is superior to analogue display system, such as a chart recorder, since it provides a logical method of presentation and analysis of data from long term monitoring. PMID- 1855366 TI - Is there a future for engineering in medicine? PMID- 1855368 TI - Atypical pneumonia syndromes. PMID- 1855367 TI - A pattern-oriented approach to chest radiographs in atypical pneumonia syndromes. AB - The differential diagnosis of the atypical pneumonia syndrome is facilitated by recognition of the chest radiographic pattern. Both infectious and noninfectious entities should be considered: clinical criteria may be used to exclude unlikely diseases and to construct an ordered list of possible causes. PMID- 1855369 TI - Infections with Chlamydia pneumoniae strain TWAR. AB - Chlamydia pneumoniae has recently been recognized as an important cause of respiratory tract disease, including atypical pneumonia. Serosurveys suggest that C. pneumoniae is endemic in most countries and is capable of causing outbreaks and epidemics of pneumonia, especially in countries where the antibody prevalence is relatively low. The population incidence of infection appears to be cyclical, with approximately 4-year cycles in the US (Seattle) and 6-year cycles in Denmark having been demonstrated. Pneumonia caused by the organism is unusual in young children in developed countries but may be an important cause of lower respiratory infections among children in developing and tropical countries. In otherwise healthy adults, C. pneumoniae pneumonia usually can be treated effectively on an outpatient basis. Patients with C. pneumoniae pneumonia often have a gradual onset of symptoms: a sore throat and hoarseness followed by a cough. Auscultatory and radiographic findings usually are prominent, even in patients with mild disease, and a cough and malaise may persist for several weeks or more after appropriate therapy. Microimmunofluorescence serologic testing is available in only a few laboratories. However, the new HL cell line holds promise of making culture and isolation of C. pneumoniae more widely available. Questions remain about the routes of transmission of C. pneumoniae, its incubation period, its role in lower respiratory disease in children in developing countries, the optimal antibiotic therapy, the existence and importance of chronic and latent C. pneumoniae infections, and the organism's association with nonrespiratory tract disease. PMID- 1855370 TI - Legionella infection. AB - As specialized laboratory tests became more widely available, Legionella species were found to be common causes of nosocomial and community-acquired pneumonia. Patients with chronic lung disease and organ transplants are at greatest risk. Clinical manifestations are non-specific, although fever greater than 39 degrees C and diarrhea are common. Erythromycin remains the antibiotic of choice, although many alternative agents are available. Once cases are discovered, a search for the organism in water distribution systems and respiratory equipment can be fruitful. Disinfection of water distribution systems by superheating and flushing or by hyperchlorination is feasible. PMID- 1855371 TI - Aspiration pneumonia. AB - The clinical presentation and course of chemical pneumonitis after inhalation of gastric contents ranges from mild and self-limited to severe and life threatening, depending on the nature of the aspirate and the underlying condition of the host. In the absence of witnessed inhalation of vomit, diagnosis is difficult and requires a high index of suspicion in a patient who has risk factors for aspiration. In the absence of an obvious predisposition, the abrupt onset of a self-limited illness characterized by dyspnea, cyanosis, and low-grade fever associated with diffuse rales, hypoxemia, and alveolar infiltrates in dependent lobes should suggest aspiration. Treatment consists of supportive care with high-flow oxygen and volume replacement. Bacteria usually play no role in the initial lung injury, and antibiotics should be withheld until there is evidence of superinfection. Prophylactic corticosteroids should not be used. Preventive measures should be employed in patients at high risk for aspiration. Patients with unexplained chronic respiratory syndromes should be evaluated for gastric regurgitation and aspiration. PMID- 1855372 TI - Atypical pneumonia and environmental factors. Where have you been and what have you done? AB - The wide variety of conditions described in this paper emphasizes the potential importance of occupational, environmental, travel, and avocational history in the correct diagnosis of lung disease (Table 3). The focus of attention in this paper is quite clearly North America and other developed countries. To expand this discussion to include illnesses limited to the underdeveloped regions of the world would require a treatise of tropical and geographic medicine. Many times, these "exotic" circumstances can be dismissed in relatively short order. Detailed interrogation of a sick patient with pneumonia will be impossible in many cases. Nevertheless, if the clinical picture does not fall rapidly in line with the more common causes of pneumonia, consideration of these "unusual" causes of the syndrome may be essential. PMID- 1855373 TI - Slowly resolving, chronic, and recurrent pneumonia. AB - Slowly resolving, chronic, and recurrent pneumonias are clinical patterns that are often misunderstood and mistreated. This article reviews the natural history, clinical presentation, roentgenography, bacteriology, and relation to underlying illnesses of each of these atypical forms of community-acquired pneumonia. Standard definitions are presented and provide the physician with a means to classify the pneumonias. Appropriate diagnostic evaluation and therapy are also discussed. PMID- 1855374 TI - Atypical manifestations of pneumonia in the elderly. AB - This article focuses on the features of common lower respiratory-tract infections in the elderly, specifically those age-associated physiologic and immunologic changes that alter the classic clinical picture of infection. Attention is directed at the epidemiology and clinical features of pneumonia in community, institutionalized, and hospitalized individuals. Those treatment factors unique to an elderly patient are discussed. PMID- 1855375 TI - Community-acquired fungal diseases. AB - The endemic mycoses--histoplasmosis, blastomycosis, and coccidioidomycosis-pose a common problem in the differential diagnosis of the atypical pneumonia syndrome. Careful exposure-and-travel history frequently serves as a strong clue to aid diagnosis. Careful interpretation of serologic data may be useful but seldom timely. In critically ill patients, invasive diagnostic tests are frequently needed. PMID- 1855376 TI - Tuberculosis and the atypical pneumonia syndrome. AB - Literature over the last 30 years has warned of the atypical or unusual characteristics of pulmonary TB. Shifts in the demographic distribution of the disease in the US are ascribed in part to the occurrence of HIV disease outbreaks in group settings, and to recent influxes of immigrants from developing countries. Unsuspected pulmonary TB is particularly common among the elderly. Socioeconomic categories not traditionally thought of as being high risk also are affected. In the low-risk setting, TB can be treacherous because misdiagnosis is likely. Tuberculosis is a great mimicker, and it can appear to be any acute community-acquired pneumonia such as atypical pneumonia. Symptoms and signs are few. A high index of awareness is therefore essential. The approach to atypical pneumonia emphasizes the need to include TB in the differential diagnosis to be aware of the total disease spectrum of TB and understand the risk factors. The atypical pneumonia syndrome is only a portion of the clinical spectrum of TB. PMID- 1855377 TI - Noninfectious pulmonary diseases masquerading as community-acquired pneumonia. AB - A wide spectrum of pulmonary disorders may manifest clinical and radiographic features consistent with infectious pneumonitis. Bronchiolitis obliterans, eosinophilic pneumonia, hypersensitivity pneumonitis, pulmonary vasculitis, alveolar hemorrhage, and alveolar proteinosis all may be difficult to distinguish from community-acquired pneumonia. The salient clinical features of these disorders are reviewed in this article. In addition, specific diagnostic and therapeutic approaches that may aid in differentiating these unusual diseases from the pulmonary infections they mimic are outlined. PMID- 1855378 TI - Oral antibiotics for pneumonia. AB - The majority of patients presenting with community-acquired pneumonia can be treated with oral antibiotics and can be managed successfully as outpatients. Oral-antibiotic selection requires a knowledge of the classes of antibiotics available, utility of diagnostic testing, epidemiology of pneumonia, and a rational approach to empiric therapy when a cause cannot be immediately identified. These topics are reviewed, with the goal improved therapeutic efficacy in the oral treatment of pneumonia. PMID- 1855379 TI - Contraceptive female sterilization in Alabama: a replication of the WHO study. AB - The prevalence of female sterilization for contraceptive purposes has grown rapidly throughout the world, and is especially high in the United States. Yet the psychosocial impact of female sterilization is incompletely understood. Much of the previous research has been retrospective and has lacked comparison groups of women using other methods. Better designed, prospective studies have been needed, and the World Health Organization's Collaborative Prospective Study of Female Sterilization was conducted to address this need. No evidence was found in the WHO study of a significant impact of tubal ligation compared to other contraceptive methods on mental health, menstruation, or sexual satisfaction. The present study, a replication of the WHO study, compared 323 Alabama women undergoing elective contraceptive sterilization with 318 women using other techniques to control fertility. In general, the results supported the WHO study conclusions. Although sterilization produced a small increase in menstrual distress in Alabama, there were no significant differences between sterilization and comparison women in mental health or sexual satisfaction. PMID- 1855380 TI - Contraceptive efficacy of lactational amenorrhea in urban Chilean women. AB - The contraceptive efficacy of breastfeeding was assessed in 236 healthy urban women who were followed at monthly intervals during the first postpartum year. Proportional hazard models were used to evaluate the influence of time postpartum, menstrual status and breastfeeding pattern upon the risk of pregnancy. Time and menstrual status had a highly significant effect on this risk. Those women who remained in amenorrhea had cumulative probabilities of pregnancy of 0.9% and 17% at 6 and 12 months postpartum, respectively. In those who recovered menstrual cycles, the risk rose to 36% and 55% at 6 and 12 months, respectively. Milk supplementation also increased significantly the risk when considered alone but not when time and/or menstrual status were included in the analysis. However, amenorrheic women who introduced bottle feeding, had a higher risk of pregnancy after 6 months postpartum than those who remained fully nursing. The analysis was unable to detect a significant influence of the nursing frequency. The results confirm that lactational amenorrhea is an effective contraceptive during the first six months postpartum. The first postpartum bleeding marks a great increase in the risk of pregnancy. Supplementation also increases the risk, particularly in amenorrheic women. PMID- 1855381 TI - A pilot study on family spacing attitudes and practices in rural Gezira. AB - The attitudes towards, and practice of, modern contraception among the rural population of the Gezira area of the Sudan were analyzed using a structured questionnaire. This was part of a comprehensive community survey carried out by the Faculty of Medicine, University of Gezira, Sudan, as part of a rural development program. Eight villages belonging to the Sennar Sugar Scheme were included in the survey. The result showed a low percentage of contraceptive users in all villages. The main reasons given by mothers for not using contraceptives were that contraceptives were against religion, mothers had not heard about them, mothers wanted more children, and contraceptives were not available. These villages were also characterized by high illiteracy rate and large family size. There is a need for health education concerning child spacing. This should be combined with religious education by religious leaders to remove misunderstandings concerning modern contraceptive use. Adult education programs, especially for females, will also have an impact. PMID- 1855382 TI - Parsimonious systems description for predictive modeling in cardiovascular medicine. PMID- 1855383 TI - Action of low-intensity laser radiation on Escherichia coli. AB - The review deals with quantitative laws of monochromatic visible light action on the cellular level, as well as with the primary photoacceptors and possible light signal transduction chains in bacterial cell Escherichia coli WP2 trp-. Experiments described in this paper are a part of experimental work performed for explaining the molecular mechanism of low-intensity laser therapy. The existence of certain parameters of light (dose, intensity, pulse repetition rate, monochromaticity within the absorbtion bandwidth of biomolecules) for stimulation of E. coli WP2 metabolism has been established. The necessity for a certain physiological state of bacteria cells sensitive to irradiation has been shown. The sensitivity of bacteria to irradiation with monochromatic visible light has been proposed to be a delta pH-dependent genetic process. PMID- 1855384 TI - Human postural dynamics. AB - The study of posture dynamics is important not only to understand disorders of impaired equilibrium and protective reactions to unexpected displacements of the human body, but also to the design of prosthesis and functional neuromuscular stimulation as aids to patients with impaired postural stability and locomotion. Coordinated control of the body segments is a complex aspect of motor behavior, owing to the multiple degrees of freedom of the controlled system. Several interacting subsystems are involved in the dynamics of human posture and locomotion, including the skeletal, neuromuscular, and sensory systems. Human posture control is maintained by somatosensory, vestibular, and visual feedback, integrated within the locomotor and central nervous systems. Studies of posture dynamics and stability therefore entail the study of mechanical aspects of the human body, its sensory systems, and the principles governing coordination in motion control. In this paper is reviewed some of the research done in the field of human posture dynamics, including such topics as biomechanics, equilibrium, stability, motion coordination, neural feedback, neural control systems modeling, motion strategies, optimality of motion, and adaptation. We consider experimental approaches and theoretical models, as well as the gap between them. Principles for the experimental investigation of control systems are considered. PMID- 1855385 TI - Centric-fusion translocation and whole-arm heterochromatin in the karyotype of the blue fox (Alopex lagopus L.): synaptonemal complex analysis. AB - Conventional observations of mitotic chromosomes from two male blue foxes, revealing a centric-fusion translocation and whole-arm heterochromatin, were verified by synaptonemal complex analysis. This analysis revealed that the centric fusion had been preceded by a conspicuous loss of chromosome material in the two one-armed chromosomes involved, but the chromosomal origin of the centric fusion kinetochore could not be established. The nontranslocated chromosomes of the trivalent, which in all cells but one were in cis configuration, had reached by early pachytene a stage in which almost complete homologous pairing and nonhomologous association or pairing of the free ends of the chromosomes could be observed. In later stages, complete pairing of the nontranslocated chromosomes with the corresponding arms of the centric-fusion translocation was seen occasionally. One to six autosomal bivalents demonstrated unpaired heterochromatic arms in early pachytene, and the heterochromatic chromosome arms were sometimes unpaired even in late pachytene. Some of them showed a distinct size heteromorphism in late zygotene and early pachytene. In most late-pachytene cells, however, the heteromorphic chromosomes were completely length-adjusted. Only a small fraction of the cells showed pairing interference between nonhomologous chromosomes. PMID- 1855386 TI - A t(X;15)(q23;q25) with Xq reactivation in a lymphoblastoid cell line from Fanconi anemia. AB - A t(X:15)(q23;q25) was detected during cytogenetic investigation of a lymphoblastoid cell line established from a female patient with Fanconi anemia. The translocation was apparently balanced at passage 300 and unbalanced at passage 13. A chromatid exchange between both the normal and the der(15), between the centromere and band 15q25, may explain these results. Replication studies, following BrdU incorporation, indicate that the segment Xq23----qter from the der(15) is early replicating whereas segment Xpter----q23 from the der(X) is late replicating. Since the normal X was early replicating, it is concluded that the segment of the long arm of chromosome X, separated from its inactivation center by the translocation, was reactivated. This interpretation is confirmed by the methylation patterns of the hypoxanthine phosphoribosyltransferase gene (HPRT), mapped on Xq26, which corresponds to that of an active gene, whereas that of phosphoglycerate kinase (PGK1), which remained on the der(X), corresponds to that of an inactive gene. This is the first example of reactivation of a segment of the X chromosome following a structural rearrangement in somatic cells. PMID- 1855387 TI - A fluorescence in situ hybridization technique for retrospective cytogenetic analysis. AB - Fluorescence in situ hybridization (FISH) is being used increasingly in clinical practice; however, current FISH techniques require fresh material, and there is considerable variation in hybridization efficiency between laboratories. We have modified a FISH technique described by Pinkel et al. (1986) that works not only on freshly G-banded material but also on cytogenetic preparations ranging in age from 2 wk to 12 yr. We have tested this technique on several centromeric alphoid satellite probes (D1Z5, D7Z1, D17Z1, DXZ1, and DYZ3) and one noncentromeric minisatellite probe (D1Z2). Our average hybridization efficiency on freshly banded preparations for these probes is consistently greater than 90%. The combination of higher efficiency and the ability to perform hybridization on previously G-banded material makes this a valuable technique for retrospective analyses. PMID- 1855388 TI - DNA sequences surrounding the centromere of chromosome 21. AB - The mapping and sequencing of two clones that surround the centromere of chromosome 21 are presented. These clones specify the most proximal known low order repeat on 21p (p21-7D) and the most proximal known single-copy sequence on 21q (pUT-B37 at locus D21S120). PMID- 1855389 TI - Fine mapping of human 5S rRNA genes to chromosome 1q42.11----q42.13. AB - The human 5S rRNA genes have been localized by in situ hybridization to metaphase chromosomes. Tritiated RNA probes were made by transcription from 2.300-bp and 638-bp DNA fragments containing an isolated human 5S rRNA gene. Hybridization to metaphase spreads from a balanced reciprocal translocation carrier, 46,XX.t(1:7)(q42.13;p11.1), showed that the 5S rRNA genes were entirely localized on the normal and the derivative chromosome 1. This narrows the chromosome position of the major fraction of 5S rRNA genes and pseudogenes to the region 1q42.11----q42.13. PMID- 1855390 TI - Localization of the human gene for 230-kDal bullous pemphigoid autoantigen (BPAG1) to chromosome 6pter----q15. AB - Chromosome mapping of the human gene encoding the 230-kDal autoantigen of an autoimmune skin disease, bullous pemphigoid, was performed using flow-sorted human chromosomes of cells of normal karyotype and cells carrying a reciprocal translocation t(6;16)(q15;q24). The cDNA of the autoantigen hybridized with intact chromosome 6 and translocation chromosome 6p- (6pter----q15::16q24--- qter). The gene (BPA230) was located to the chromosome region 6pter----q15. PMID- 1855391 TI - The gene for human growth hormone-releasing factor (GHRF) maps to or near chromosome 20p12. AB - Growth hormone-releasing factor (GHRF), a hypothalamic releasing factor also named somatocrinin, influences the secretion and synthesis of growth hormone. Human GHRF is encoded by a single gene which was assigned to chromosome 20 by dot blot analysis of DNA from dual laser sorted chromosomes. Using a radioactive cDNA probe, we localized the GHRF gene to chromosome 20p12 or near band 20p12. PMID- 1855392 TI - Comparison of RBG-banded karyotypes of cattle, sheep, and goats. AB - The karyotypes of the three main domestic Bovidae species. Bos taurus, Ovis aries, and Capra hircus, have been investigated by RBG-banding. Primary fibroblast cells were cultured from fetal lung or muscle tissue and collected for chromosome preparation after double thymidine synchronization. Depending on the culture and species, BrdU and FdU were added for 8-11 h or 7-10 h, respectively, before harvest. The chromosomes of the three species were classified and numbered according to standard conventions (ISCNDA, 1989) and compared at different stages of condensation. Within the resolving power of the images obtained, the RBG banding patterns appear to be very similar, with only minor differences existing between chromosome 9 and the sex chromosomes of cattle and the same chromosomes in the domestic sheep and the goat. PMID- 1855393 TI - Achiasmatic giant sex chromosomes in the vole Microtus cabrerae (Rodentia, Microtidae). AB - Conventional and microspread preparations of Microtus cabrerae spermatocytes were made to investigate the chromosomes of this species. Three different types of Y chromosomes, varying in size of the heterochromatic block, were observed; they were alike, however, in regard to synapsis, which was consistently absent. Our results suggest that the heterochromatic blocks are not involved in the lack of synapsis and that asynapsis is a cytological feature common to all species of the family Microtidae. In addition, the co-aligned configuration of the ends of the sex-chromosome axes of this species and the lack of silver-stainable threads or filaments connecting them suggest the existence of two mechanisms for association of the sex chromosomes during prophase I and metaphase I: attachment of the ends of both sex chromosome axes to the nuclear envelope and heterochromatin "stickiness." PMID- 1855394 TI - Confirmation, via in situ hybridization, of the occurrence of Robertsonian translocations during lemur evolution by localization of GLUDP1 DNA sequences on lemur chromosomes. AB - A human genomic DNA sequence derived from glutamate dehydrogenase pseudogene 1 was used as a probe for in situ hybridization to the chromosomes of three lemur species, Eulemur fulvus mayottensis (EFU), E. macaco macaco (EMA), and E. coronatus (ECO). This sequence, which is 98% homologous to the nucleotide sequence of the gene for human glutamate dehydrogenase (GLUD), was found on homologous bands of three morphologically similar chromosome segments, EFU14, EMA5p, and ECO8q, confirming that different Robertsonian translocations occurred during the evolution of these three species. These loci on the lemur chromosomes probably correspond to the human GLUD locus. PMID- 1855395 TI - American College of Chest Physicians. 57th annual scientific assembly. November 4 8, 1991, San Francisco. Abstracts. PMID- 1855396 TI - Juvenile ageism: unrecognized prejudice and discrimination against the young. AB - Ageism is a form of prejudice and discrimination as virulent as racism and as pervasive as sexism. It has been described as it affects the elderly but has not been sufficiently recognized as it affects the young. Institutional juvenile ageism exists when social systems ignore the interests of children. Individual juvenile ageism exists when the developmental interests of a child are not respected. This article describes the dynamics, manifestations, and approaches to the amelioration of juvenile ageism. PMID- 1855397 TI - Psychological interventions after child and adolescent disasters in the community. AB - This paper describes how a community mental health center responded to requests in dealing with disasters which impacted on communities it serves. Two events are described which illustrate the theoretical understanding and practical interventions utilized. These aspects are examined in the context of selected publications on the mental health aspects of disasters. PMID- 1855399 TI - Suicidal behavior among psychiatric outpatient children: an estimate of prevalence. AB - The prevalence of suicidal behaviors displayed by pre-adolescent psychiatric outpatients has been estimated to range between 25 percent and 33 percent of the outpatient population. The current study assessed suicidal behaviors displayed by 40 children aged 12 and younger who were evaluated in a psychiatric outpatient service. According to the Pfeffer Spectrum of Suicidal Behavior Scale, 15 percent of the sample had recently engaged in some form of suicidal behavior and almost 3 percent had made a suicide attempt that was viewed as realistically endangering life. PMID- 1855398 TI - Adolescent bereavement following the death of a parent: an exploratory study. AB - Eleven healthy adolescents, ages 13-18, were followed through the year following parental death. Semi-structured interviews were used in combination with standardized measures to complete in-depth evaluations at 6 weeks, 7 months and 13 months following parental death. Teacher reports and parent interviews and reports provided additional information. Initial responses were characterized by intense emotional, cognitive, physical and behavioral reactions associated with impaired school performance, strained peer relations, and sleep disturbances. Stress related symptoms were prominent and sustained. Overall, subjects reported a higher sustained degree of distress than adult children following the loss of a parent. Prominent themes are reviewed. Implications and directions for future research are discussed. PMID- 1855400 TI - Siblings in foster care: success and failure. AB - This article reports on a retrospective study of 59 joint placements of siblings in foster homes, involving a total of 137 children. An overall picture is presented of the agencies' considerations in making these placements. The number of prematurely terminated placements in this group amounted to 14 (23.7%). Several factors that appear related to premature termination are discussed. PMID- 1855401 TI - Children's ability to remember activities performed and imagined: implications for testimony. AB - This study examined the ability of six year old children to remember activities performed or imagined when they are done alone or interactively with another person. Results suggest that children remember activities performed better than those imagined, both immediately and after an eight week delay. Activities performed interactively with another person were remembered better than those performed alone after the delay. Children provided fewer responses to open-ended than to specific questions, but their responses to open-ended questions were more likely to be correct. Responses to questions about events that did not occur were quite good initially but accuracy decreased significantly in response to follow up probes. PMID- 1855402 TI - Anticardiolipin antibodies in patients with acute myocardial infarction. AB - Fifty-six consecutive patients, 53 males and 3 females aged from 36 to 83 with a mean age of 61.0, all with acute myocardial infarction (AMI), were screened for anticardiolipin antibodies (ACA) by single sampling at time of admission to the medical intensive care unit; results were compared with those for age-matched, healthy controls. IgM and IgG-ACA were measured by an enzyme-linked immunosorbant assay technique. IgG-ACA were detected in 9 patients (16.1%); IgM-ACA were detected in 9 patients (16.1%). Only one of the patients had raised ACA of both isotypes. There was on difference in either ACA levels or frequency of ACA elevation between patients and controls. Risk factors of coronary artery disease showed no significant difference between patients with and without ACA. Low titer of IgG-ACA was found in one of ten patients with reinfarction and/or previous cerebral infarction. In conclusion, single measurements of anticardiolipin antibodies in general AMI patients are unlikely to yield diagnostically important information. The implication of occasional significant elevation of such antibodies in a general AMI population remains to be speculated. PMID- 1855403 TI - [Improvement of the EIA kit for the detection of tetanus immunoglobulin in human sera]. AB - For the program to eliminate tetanus neonatorum in this country, we have improved the sensitivity of enzyme immunoassay kit (EIA kit) prepared on 1987 for the detection of human tetanus immunoglobulin (TIG) by competitive principle. (Chinese J Microbiol Immunol 1987; 20: 269-278) Horse-radish peroxidase conjugated to tetanus toxoid monoclonal antibody was involved in the new kit, and tetanus hybridoma clones were prepared by this laboratory. The lowest detectable TIG level is 0.05 IU/ml serum instead of 0.1 IU/ml serum. The dose-response curve and cut-off determination system of the new EIA kit are better than those of the original one. We proposed that the newly designed EIA kit could be used for understanding the TIG level in women who are in the age group for giving birth and in the tetanus vaccination group. PMID- 1855404 TI - Anaerobic growth and oxygen toxicity of Rhizopus cultures isolated from starters made by solid state fermentation. AB - To explore the relationship between Rhizopus growth and its microaerophilic characteristics the present study was undertaken. A survey of 18 Rhizopus cultures growing in anaerobic or microaerobic condition found that 11 of the cultures grew quite well under microaerobic condition, but all the cultures grew poorly under absolutely anaerobic condition. Among the 18, 8 showed definitely banded mycelial growth below the surface of the medium in the tube. Six of 18 cultures--RT-1-8, RT-43, RT-46, A-1, C-1, and E-1--grew with much aerial hyphae when they were cultivated on media supplemented with different detoxifying agents under aerobic condition. These six strains are comparatively sensitive to oxygen toxicity (H2O2 or O2- or OH.) under aerobic condition, as many microaerophilic bacteria are. There were nine strains whose aerial hyphal growth was greatly enhanced by the presence of Aspergillus niger catalase. However, the growth of the majority of the cultures was not influenced by supplements of bovine liver catalase or bovine liver superoxide dismutase. In conclusion, some Rhizopus cultures from the starters exhibited both microaerophilic and aerobic growth. The phenomena of growth in low O2 condition, and the subsurface growth of mycelia in tubes, may provide a clue to exploitation of the microaerophile-like characteristics in some starter molds. PMID- 1855405 TI - [Combined methods of dialysis, cooked meat medium enrichment and laboratory animal toxicity for screening Clostridium botulinum spores in honey and infant food]. AB - One hundred and fifty two samples of honey were purchased from apiaries and markets in Taiwan, meanwhile fifty samples of infant food including powders of infant milk, wheat, rice and commercial mixed cereals, as well as juice had been bought from supermarkets in Taipei city from July 1988 through April 1989. The samples were used for detecting the presence of Clostridium botulinum spores. Honey samples were prepared by dialysis to obtain the bacterial spores; however, infant food had been innoculated directly into the cooked meat medium. The suspicious isolated colonies were identified by Vitek automatic microbial identification system. The supernatants of cooked meat medium enrichment were performed for typing botulinum toxins via the laboratory animal toxicity test. The results showed that two samples of honey contained the spores of C. botulinum type B, but none in samples of infant food. The specific response of clinical signs in mice, after being administered the supernatant of suspected cultural broth, were also observed and described in this article. PMID- 1855406 TI - Mouse dander-allergic bronchial asthma--a case report. AB - A case of mouse dander-allergic bronchial asthma is reported. A 47-year-old female professor of pharmacy has experienced severe chest discomfort, dyspnea and wheezing, and itching nose and eyes each time when she contacted with mice in recent months although she has done animal (mouse) experiments for many years without any difficulty. Those symptoms usually recovered spontaneously after removing the mice or using bronchodilator. The causal relationship between mouse dander and bronchial asthma was established, in addition to history of exposure, by a positive skin test, a strong RAST and overwhelming bronchial provocation test. The allergen was identified, by SDS-PAGE and immunoblotting to be a 21 Kd molecule. PMID- 1855407 TI - Critical periods in brain development. AB - The growth of the brain after organogenesis can be described as occurring in two somewhat overlapping phases: a phase of neuronal multiplication followed by one of glial proliferation, during and after which occur myelination and dendritic and axonal arborization. Within this gross chronology is a finer-grained chronology, with, for instance, different neuronal populations dividing at different times. The course of brain development can be affected by a variety of factors, the nature and extent of the perturbation dependent on the timing of the treatment with respect to stage of brain development. Growth processes completed before treatment are unaffected. Only those processes occurring at the time of the treatment are affected, plus some later-occurring processes, as a result of a cascade of effects. These concepts are examined briefly with reference to ionizing radiation, hormones and environmental stimulation and more fully with respect to nutrition. Undernutrition appears to depress the rate of all brain growth processes contemporaneous with it to the same extent. Whether the effects produced are likely to be permanent is discussed, together with the possibility that there may be mechanisms that attenuate or compensate for adverse effects. PMID- 1855408 TI - Sensitive and vulnerable periods in the development of the visual system. AB - In advanced mammals the visual system consists of a number of parallel channels for the efficient processing of different aspects of the visual scene. Much of the basic anatomical structure of the visual pathway is constructed before birth. A wave of maturation sweeps through the system, from the eye to the visual cortex, the correct formation of connections depending on precisely timed interactions between axons and their targets. Competition between growing axons (apparently dependent on spontaneous impulse activity in those axons), cell death (partly influenced by competition between those cells' axons), axon withdrawal, trophic interactions--these and other mechanisms play a part in constructing the visual pathway and laying down basic 'maps' of the visual field before birth. Disturbances in such processes might underlie disorders of the genesis of the nervous system. At the level of the visual cortex, synaptic plasticity continues after birth and may permit cortical neurons to refine their processing capacities on the basis of information provided by the visual environment. This makes the young animal vulnerable to disturbances of visual experience early in life, which can cause virtually irreversible deficits in stereoscopic vision, visual resolution and sensitivity to contrast (amblyopia) in adult life. PMID- 1855409 TI - Fetal brain development and later schizophrenia. AB - Computed tomography and magnetic resonance imaging studies have shown cerebral ventricular enlargement and a decreased volume of temporal lobe structures in a proportion of schizophrenic patients. Neuropathological investigations confirm these findings and also show diminished volume of the hippocampus and abnormal pre-alpha cell clusters in the parahippocampal gyrus. Compared with controls, schizophrenic patients are more likely to have minor physical anomalies, to have a history of obstetric complications, and to have been born in the late winter. Together the evidence regarding structural brain abnormalities and epidemiology suggests that a significant proportion of cases of schizophrenia have their origins in fetal or neonatal life. The mechanisms involved in the aberrant neurodevelopment remain obscure but some impairment of neuronal migration is an appealing hypothesis. PMID- 1855411 TI - Early stress and adult emotional reactivity in rhesus monkeys. AB - This chapter examines the relationship between early social experiences and behavioural and emotional reactivity in adolescence and adulthood that has been established through extensive research with rhesus monkeys. Classic studies carried out in the 1960s first demonstrated that rearing under conditions of social isolation resulted in severe behavioural abnormalities that carried over into adulthood. In the 1970s techniques for reversing such isolation-induced deficits were developed. More recent studies have examined the long-term consequences of more subtle variation in early rearing environments. Monkeys reared from birth without mothers but with extensive peer contact develop relatively normal social behavioural repertoires and function well in familiar and stable social settings. However, peer-reared monkeys display extreme behavioural and physiological reactions to environmental challenges, such as brief social separation, later in life. In contrast, monkeys reared by unusually nurturant foster mothers appear to develop effective strategies for coping with subsequent environmental challenges. Some general principles that have emerged from these studies with rhesus monkeys will be outlined and their implications regarding possible relationships between early social experiences and responses to challenge later in life in humans will be discussed. PMID- 1855410 TI - Fetal response to intrauterine stress. AB - Many human infants are born inappropriately small as a result of stress suffered during intrauterine life. Acute reductions in oxygen delivery to fetal tissues have therefore been studied in animals so that insight can be obtained into the adaptive mechanisms that underlie human developmental abnormalities. It is now known that during moderate hypoxic stress fetal arterial blood pressure is variably increased while heart rate and cardiac output are depressed; blood volume is reduced but cardiac output is redistributed to spare the myocardium, brain and adrenal glands at the expense of most other organs. Also a greater fraction of oxygen-rich venous blood from the placenta is returned to the heart for distribution. Spared organs are those that grow disproportionately well in human asymmetrical intrauterine growth retardation (IUGR). These cardiovascular responses are not fully understood although elevated fetal plasma levels of catecholamines and a host of fetal hormones are undoubtedly important. Chemical sympathectomy does not abolish the blood flow redistribution phenomenon, which implies that autoregulatory effects may be responsible for some of the redistribution of blood flow. Fetal hypoxaemia and metabolic abnormalities are sequelae often found with human IUGR, suggesting placental exchange defects. IUGR placentas appear to have defective transport mechanisms for many nutrients. Animal studies suggest that the placenta will give priority to its own needs over those of the fetus, when necessary, to support its own growth and function. PMID- 1855412 TI - Childhood experiences and adult psychosocial functioning. AB - Various studies have shown statistically significant associations between adverse experiences in childhood and abnormal psychosocial functioning in early adult life. It should not be assumed that this finding necessarily means an enduring effect of early experience. Part of the explanation is that adverse environments tend to be persistent and, hence, that what is being reflected is simply continuity in risk factors. But even when such continuity is taken into account, substantial associations over time remain. Using data from two long-term longitudinal studies a variety of possible mediating mechanisms are considered and shown to be operative. These include: an immediate effect leading to emotional/behavioural disturbance in childhood that then persists into adult life (this mechanism may be more important than appreciated hitherto, because heterotypic continuity has concealed the strength of the persistence of disturbance); one risk environment increasing the likelihood of occurrence of a second, different risk environment; the establishment of patterns of behaviour that bring about later risk environments; and the development of an increased vulnerability to later risk environments. PMID- 1855413 TI - Prolegomena to a model of continuity and change in behavioural development. AB - It is now widely acknowledged that personality and behaviour are shaped in large measure by interactions between the person and the environment. There are many kinds of interaction but we suggest that three types play particularly important roles both in sustaining behavioural continuity across the life course and in guiding the trajectory of the life course itself. Reactive interaction occurs when different individuals exposed to the same environment experience it, interpret it and react to it differently. Evocative interaction occurs when an individual's personality evokes distinctive responses from others. Proactive interaction occurs when individuals select or create environments of their own. Within this framework we also examine systematic change and turning points in behavioural development. We have recently advanced a paradoxical theory suggesting that behavioural continuities are especially likely to be evident during periods of social discontinuity; that is, dispositional factors influence behaviour most when individuals enter new situations and assume new statuses. This model receives empirical support from both experimental and longitudinal correlational research. The model also presents interesting implications for our understanding of turning points in behavioural development: to effect change in the life course, new situations must eliminate old options and create new opportunities. Convergent evidence from experimental and naturalistic designs is introduced to support this claim. PMID- 1855414 TI - The intrauterine environment and adult cardiovascular disease. AB - Two recent findings suggest that maternal nutrition, and fetal and infant growth, have an important effect on the risk of cardiovascular disease in adult life. (1) Among 5225 men who were born in Hertfordshire, England during 1911-1930 and who were breast fed, those who had the lowest weights at birth and at one year had the highest death rates from cardiovascular disease. The differences were large and were reflected in differences in life expectancy. (2) In England and Wales there is a close geographical association between high death rates from cardiovascular disease, and poor maternal physique and health, and poor fetal growth. These findings raise the question of what processes link the intrauterine and early postnatal environment with risk of cardiovascular disease. Blood pressure, a known risk factor for cardiovascular disease, is one link. A recent study of 449 men and women now aged 50 showed that measurements at birth predicted blood pressure more strongly than current measures such as body mass. Levels of clotting factors in the blood and serum cholesterol (two other risk factors) may also be links. PMID- 1855415 TI - Programming by early nutrition in man. AB - Whether early diet influences long-term health or achievement is a key question in nutrition. Such long-term consequences would invoke the concept of 'programming'--a more general process whereby a stimulus or insult at a critical period of development has lasting or lifelong significance. Data from small mammals and primates show that early nutrition may have potentially important long-term effects, for example on blood lipids, plasma insulin, obesity, atherosclerosis, behaviour and learning. Corresponding studies in man have been largely retrospective and difficult to interpret. The preterm infant is however an important model for human research because formal random assignment to early diet is practical. A large prospective randomized multicentre study has been undertaken on 926 preterm infants to test the hypothesis that early diet influences long-term outcome. Diets included human milk, standard formula and nutrient-enriched preterm formula. The diet consumed for on average the first month post partum had a major impact on subsequent developmental attainment, growth and allergic status in early childhood. That such a brief period of dietary manipulation has lasting significance implies that the neonatal period is critical for nutrition after preterm birth. These data may have broader implications for human nutrition. PMID- 1855416 TI - Programming of cholesterol metabolism by breast or formula feeding. AB - We tested the hypothesis that breast or formula feeding and cholesterol intake during the neonatal period influence cholesterol metabolism and arterial fatty streaks in young adult baboons. Genetic variation was controlled by randomly assigning half-sib sire progeny to a factorial dietary design. We measured serum cholesterol and lipoprotein cholesterol concentrations enzymically and cholesterol production and bile acid excretion rates isotopically. The bile cholesterol saturation index was calculated from enzymic analyses of cholesterol, bile salt and phospholipid concentrations in gallbladder bile. Breast-fed baboons had higher serum VLDL + LDL cholesterol/HDL cholesterol ratios in the early postweaning period (six months) until adulthood (7-8 years) than formula-fed baboons. In adulthood a high cholesterol diet increased bile acid excretion by approximately 40% in formula-fed baboons but did not significantly increase the bile acid excretion rate among breast-fed animals. Adult baboons breast fed as infants also had an approximately 8% lower cholesterol production rate than formula-fed animals and a 20% higher bile cholesterol saturation index. The level of cholesterol in the infant formulas influenced cholesterol metabolism in adulthood but not serum lipoprotein concentrations. As young adults, breast-fed baboons had more extensive arterial fatty streaks than formula-fed baboons. This difference could be accounted for by differences in the lipoprotein ratios. These results demonstrate that breast and formula feeding differentially modify cholesterol metabolism. This may influence the development of chronic diseases. PMID- 1855417 TI - Interactions between early nutrition and the immune system. AB - The ontogenetic development of the immune system is a well-defined, almost stereotyped event. The anlagen of the human thymus can be distinguished in the third and fourth branchial arches in the sixth week of gestation. Several distinct responses have been observed in the first trimester of fetal development. In addition to genetic factors, environmental influences such as nutrition play an important role in influencing the developing human immune system. Adverse factors that impair fetal growth hinder immunological maturation as well. These include maternal malnutrition, smoking, alcohol and other substance abuse, placental insufficiency and infection. The immunocompetence of low birth weight infants is compromised; those who are small for gestation show persistent immunological impairment for several months, even years. Prolonged effects on immune responses can be seen in animal models of fetal malnutrition. A second area where interactions occur between dietary factors and the immune system is the IgE-mediated allergic response. Those with a family history of atopy are at high risk of developing allergic disease in late childhood and adult life. The enormous costs of atopic disease in terms of health management and physical and emotional isolation have led to attempts at prevention. These strategies include restriction of the mother's diet during pregnancy and lactation to exclude common allergenic foods and prolonged exclusive breast feeding. Casein or whey hydrolysate formulas are advisable in those not breast fed. PMID- 1855418 TI - Childhood infection and adult disease. AB - In England and Wales there is a strong geographical relation between current mortality from chronic bronchitis and emphysema in adults and infant mortality from bronchitis and pneumonia 50 years ago. Follow-up studies of infants and children show that certain pulmonary infections cause persisting abnormalities of lung function. This suggests that infection of an organ system during a period of rapid growth may have permanent deleterious effects. Long-term consequences of infection may also depend on age-related differences in the host response. The relationship between age of infection with hepatitis B virus and the likelihood of becoming a chronic HBsAg carrier is an example of this. Evidence that the common communicable diseases of childhood tend to have occurred late in cases of multiple sclerosis hints at similar mechanisms in this disease. The current patterns of motor neuron disease mirror the epidemiology of poliovirus infection 40 years ago both in geographical distribution and in changes over time. The same neuronal populations are affected in both these conditions; is there a causal link? PMID- 1855419 TI - Surgical repair of rectovaginal fistulas in patients with Crohn's disease: transvaginal approach. AB - The surgical management of rectovaginal fistulas complicating Crohn's disease has been associated with unacceptably high failure rates. We sought to modify the available surgical techniques to provide a solution to this challenging problem. Between December 1983 and January 1990, 14 patients with Crohn's disease underwent repair of a rectovaginal fistula. A modified transvaginal approach was employed by the authors. A diverting loop ileostomy was performed on all patients, either as the initial step in the staged management of intractable perianal disease or concurrent with the repair of the rectovaginal fistula. The fistula was completely eradicated in 13 of the 14 women and did not recur during the mean follow-up period of 55.0 months (range, 3-77 months). Intestinal continuity was reestablished in these 13 patients within 6 months after the initial fistula repair. One patient with a very low-lying fistula constituted our only failure. We have found the transvaginal method preferable to the transanal approach because of the relative ease in raising the vaginal flap as compared with a flap of fibrotic and inflamed anorectal mucosa. On the basis of this study, we conclude that a modified transvaginal approach is an effective method for repair of rectovaginal fistulas secondary to Crohn's disease. PMID- 1855420 TI - Pilonidal disease: 25 cases treated by the Dufourmentel technique. AB - Twenty-five patients with pilonidal disease were treated by the Dufourmentel technique between 1984 and 1989. In this series, 18 patients (72 percent) were women and 7 (28 percent) were men (mean age, 24 years); hospital stay averaged 4 days. There were no recurrences and no reports of surgical wound infection. Diagnosis was confirmed histologically in all cases. PMID- 1855421 TI - Consequences of ileal pouch-anal anastomosis for Crohn's colitis. AB - Patients with Crohn's colitis are generally not considered candidates for the ileal pouch-anal anastomosis (IPAA) procedure. We reviewed 362 consecutive patients undergoing IPAA and analyzed the outcome of this procedure on 25 patients with a preoperative diagnosis of mucosal ulcerative colitis who were subsequently proven to have Crohn's disease. The mean follow-up was 38.1 months. Sixteen patients have a functioning pouch, seven have required pouch excision, one is diverted, and one has died. Only one of nine patients in whom there was a preoperative clinical feature suggestive of Crohn's disease has a functioning pouch, with complications uniformly occurring within months of ileostomy closure. In contrast, 15 of 16 patients without preoperative features of Crohn's disease have maintained their pouch, generally with good results. These data suggest that patients in whom there is clinical and pathologic evidence of Crohn's disease do very poorly without meaningful symptom-free intervals. However, patients without any clinical features of Crohn's disease, despite a histopathologic diagnosis of Crohn's colitis, have had a good outcome with IPAA thus far. PMID- 1855423 TI - Bacteriology of the anal wound after open hemorrhoidectomy. Qualitative and quantitative analysis. AB - The purpose of this study is to analyze the size of the bacterial colonies in anal wounds after open hemorrhoidectomy. Twenty patients were studied during predetermined postoperative time periods. Material was collected from the surface and from within the tissue of each patient's three open wounds, intraoperatively, on the 6th, 13th and 20th postoperative days for bacteriologic examination in aerobic, microaerophilic, and anaerobic media. The bacterium most commonly identified was Escherichia coli, followed by Staphylococcus aureus and Staphylococcus epidermidis. Pseudomonas aeruginosa, Enterococcus faecalis, Klebsiella pneumoniae, Proteus vulgaris, and Proteus mirabilis were also identified. Critical indexes of colonization were present since the intraoperative stage (greater than 10(5) bacteria/g of tissue and greater than 10(6) bacteria/ml); obligate anaerobic bacteria were not identified; neither the species nor the number of bacteria, even when critical indexes were present, prevented proper healing. The same bacteria were not necessarily present on the surface and in the tissue; the bacterial load observed among the three wounds (left lateral, right posterior, and right anterior), was the same. PMID- 1855422 TI - Experimental model of colon cancer: recurrences after surgery alone or associated with intraperitoneal 5-fluorouracil chemotherapy. AB - The liver is the most frequent site of metastases in colon cancer. No good animal model has been available to help improve the treatment of liver metastases or their prevention after resection of a primary colon cancer. The aim of this study was to develop a model of colon cancer induced by azoxymethane in the rat and to study the outcome after surgical resection alone or in association with intraperitoneal chemotherapy (5-fluorouracil (5-FU). Three hundred male Wistar rats received subcutaneous azoxymethane (10 mg/kg body weight/week) for 12 weeks. Eighty-three rats with isolated colon cancer underwent total colectomy; 40 of these rats with no metastases were randomized into two groups: surgery alone or surgery plus 5-FU (5 mg/kg body weight/day) for 5 days after surgery. Thirty rats were able to be evaluated. At autopsy, peritoneal carcinomatosis and liver metastases were more frequent in the control group than after adjuvant treatment with 5-FU (27.7 percent vs. 0, P less than 0.05; and 22.2 percent vs. 0, P less than 0.05, respectively). The rates of peritoneal and hepatic recurrence after resection of the primary cancer indicate that the model mimics the natural history of human colon cancer. In this model, 5-FU reduced the rate of peritoneal carcinomatosis and liver metastases but did not influence survival. PMID- 1855424 TI - Squamous-cell carcinoma of the anal canal: management with combined chemo radiation therapy. AB - Twenty patients with squamous-cell carcinoma of the anal canal received combined chemo-radiation therapy as their primary treatment. There were 18 women and two men with a mean age of 63 years (range, 34-91 years). The mean follow-up was 34 months (range, 6-62 months). Anal margin cancers and adenocarcinomas were excluded. Fourteen of 20 patients treated had a complete response. There were six local failures: three with residual disease at the end of treatment and three with recurrent disease at a later date. Of the three with residual disease, one underwent abdominoperineal resection and two received salvage therapy (one with chemo-radiation and one with radiation alone). All three patients with recurrent disease were treated with abdominoperineal resection. All six were disease free at the end of the study. Of the 14 patients with complete local response, one presented with liver metastases 19 months later. Sixteen patients (80 percent) were alive at the end of the study, and 19 patients (95 percent) had no evidence of disease. These data add support for salvage therapy in the treatment of patients with residual disease following initial chemo-radiation therapy. Salvage options for patients with squamous-cell carcinoma of the anus who fail the Nigro protocol will be discussed. PMID- 1855425 TI - Manometric and radiologic investigations and biofeedback treatment of chronic idiopathic anal pain. AB - In 12 patients suffering from chronic idiopathic anal pain, the rectosphincteric function was studied using manometric and x-ray techniques. The results of manometric investigations were compared with those obtained in 12 healthy volunteers. In all patients, the resting pressure in the anal canal was significantly higher than in control subjects. In 10 patients, defecography revealed abnormalities of the pelvic muscles. We treated the patients by using biofeedback techniques, consisting of voluntary modifications of the state of contraction of the external sphincter. In all cases, pain disappeared after a mean of eight biofeedback training sessions. When noxious manifestations had disappeared, manometry showed a significant decrease in the anal canal resting pressure. Our results indicate 1) that chronic idiopathic anal pain is associated with abnormal anorectal manometric profiles, probably resulting from a dysfunctioning of the striated external anal sphincter, and 2) that biofeedback training is an effective treatment for chronic idiopathic anal pain. PMID- 1855426 TI - DNA ploidy pattern of flat adenomas of the large bowel. AB - In an attempt to clarify the nature of "flat adenomas," DNA content was measured by means of microspectrophotometry. Thirty-nine flat adenomas (FA), 13 with mild, 22 with moderate, and 4 with severe atypia, were collected for this study. In FA, diploidy (D), polyploidy (P), and aneuploidy (A) were found 100, 0, and 0 percent in mild atypia, 41.9, 4.5, and 54.5 percent in moderate atypia, and 0, 0, and 100 percent in severe atypia, respectively. It is assumed that FA have a much higher malignancy potential than previously expected since, histologically, benign appearing FA with moderate atypia have already contained malignant DNA patterns. In particular, those more than 5 mm in diameter show aneuploidy in 80 percent. These data suggest that FA with moderate atypia play an important role in the pathogenesis of small colonic carcinomas. PMID- 1855427 TI - Assessment of the defunctioning efficiency of the loop ileostomy. AB - The defunctioning efficiency of the loop ileostomy has been assessed using a radioisotope and dye technique. The median defunctioning capacity in patients without episodes of fecal discharge per rectum (n = 18) was 99.99 percent and was not affected by body position or the formation of a dependent stoma. In patients (n = 4) who passed fecal material per rectum but who had no stomal retraction, the median defunctioning efficiency was 99.99 percent, and continued fecal discharge was considered to be due to mucopurulent secretion from active distal disease. In patients who passed fecal material per rectum and also had a retracted stoma (n = 4), the defunctioning efficiency was significantly reduced (median = 84.70 [31.2-99.10 percent; P less than 0.01]), owing to the overspill into the distal limb. Two patients underwent stomal revision, with an improvement in defunctioning efficiency to 99.99 percent. PMID- 1855428 TI - Physiologic and anatomic assessment of patients with rectocele. AB - Clinical, physiologic, and anatomic assessments were carried out in 22 female patients with symptomatic rectocele (Group A), 15 patients with asymptomatic rectocele (Group B), and 14 subjects having no rectocele (Group C). Resting and pressure, rectal pressure, rectal compliance, anorectal inhibitory reflex, and rectal sensation did not differ among the groups. Proctography revealed that the lengths of the rectocele during attempted defecation in groups A (1.6 [1.0-3.5] cm) (median and range) and B (1.6 [1.0-3.0] cm) were significantly greater than that in Group C (0.4 [0.1-0.9] cm) (P less than 0.001 in both groups). Median pelvic floor descent at rest in Groups A (4.3 [1.6-7.5] cm) (median and range) and B (4.3 [1.3-6.9] cm) were significantly greater than that in Group C (2.5 [1.2-5.0] cm) (P less than 0.001 and P less than 0.02, respectively). These results indicate that rectocele is not associated with any physiologic change apart from a significant increase of pelvic floor descent. PMID- 1855429 TI - Solitary colonic metastasis from renal-cell carcinoma 17 years after nephrectomy. Report of a case. AB - Late recurrence of renal-cell carcinoma can present many years after nephrectomy. To the best of our knowledge, we are reporting the first known case of solitary metastatic renal-cell carcinoma to the colon occurring 17 years after nephrectomy. PMID- 1855430 TI - Endometriosis in episiotomy scar with anal sphincter involvement. Report of a case. AB - A case of endometriosis in an episiotomy scar with involvement of the external anal sphincter is presented. The clinical, operative, and pathologic findings are reported. The question of etiology and treatment is discussed, and the literature is reviewed. Wide excision of the ectopic endometrial tissue with primary reconstruction of the external sphincter was curative, and the functional result was excellent. It is suggested that this treatment policy should be recommended for these cases. PMID- 1855431 TI - Use of the optical urethrotome knife in the treatment of a benign low rectal anastomotic stricture. AB - Several methods of treatment for benign anastomotic strictures following anterior resection have been described. Surgical intervention in terms of re-exploration and excision of the stricture or the formation of a permanent colostomy will be accompanied by substantial morbidity. The dilatation of these strictures without direct vision may not be safe. We describe a simple method of treating benign rectal anastomotic stricture using an optical urethrotome knife under direct vision. This technique affords an accurate incision of the stricture to increase the size of the lumen, thereby relieving obstruction. PMID- 1855432 TI - Colonoscopically guided tube decompression in Ogilvie's syndrome. AB - Ogilvie's syndrome (pseudo-obstruction of the colon) may result in gangrene and perforation of the colon if not effectively treated. Colonoscopic decompression and endoscopically guided rectal tube placement were employed to treat five patients with this syndrome who had failed medical therapy. All patients tolerated the procedure well and required no further treatment. PMID- 1855433 TI - Peritoneal seeding following potentially curative resection of colonic carcinoma: implications for adjuvant therapy. AB - Adjuvant therapeutic strategies for colon cancer are based on the knowledge of tumor recurrence patterns following potentially curative resection. Innovative methods for regional delivery of chemotherapy to the liver and peritoneal surfaces are now available to complement systemic treatment. We reviewed clinical, reoperation, and autopsy series to determine the incidence of peritoneal seeding following colon cancer resection. The data suggest a 25-35 percent peritoneal failure rate among patients that recur, indicating that intraperitoneal chemotherapy is a sensible adjuvant approach. The theory behind intraperitoneal chemotherapy and potential complications is discussed. We suggest initiation of clinical trials combining systemic and intraperitoneal chemotherapy. PMID- 1855434 TI - Anorectal manometric measurements. PMID- 1855435 TI - Glucose disposal and intermediary metabolism during one year of continuous subcutaneous insulin infusion (CSII). AB - To study the effects of CSII on insulin action and intermediary metabolism, seven type 1 diabetic patients (duration 17 +/- 4 (SEM) years), underwent sequential euglycemic clamps 1/4, 6 and 12 months after changing from conventional insulin treatment to continuous subcutaneous insulin infusion (CSII); seven healthy subjects served as controls. For at least 14 h before the study, blood glucose was maintained between 4-10 mmol/l in the patients by intravenous insulin infusion, to avoid negatively biased clamp measures. A metabolite profile was taken in the basal state and during euglycemic hyperinsulinemia. At 1/4 month insulin sensitivity was decreased in the patients (ED50 82 +/- 14 vs 52 +/- 4 mU/l in controls, P less than 0.02), whereas insulin responsiveness was normal. During the course of one year, no change towards control values was found for insulin-stimulated glucose disposal. Concomitantly, HbA1 did not change either, and remained elevated (1/4 month 11.1 +/- 0.7%, 12 months 10.0 +/- 0.9% vs 6.5 +/ 0.3% in controls, P less than 0.01). Regarding basal intermediary metabolism, triglycerides became significantly improved (1/4 month 1.32 +/- 0.13 mmol/l, 12 months 0.70 +/- 0.05 mmol/l, P less than 0.05, vs 0.70 +/- 0.08 mmol/l in controls). The acetoacetate/3-OH-butyric acid ratio increased from 0.10 at 3 to 0.26 at 12 months, which was similar to controls. The absolute levels of acetoacetate and 3-OH-butyric acid remained elevated 2-3 fold. For other basal metabolite levels no systematic trend for improvement was found for 1/4 to 12 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855436 TI - Knowledge and concerns of newly diagnosed NIDDM patients in Singapore. AB - This paper describes the findings of a questionnaire survey of the knowledge and concern of 152 newly diagnosed NIDDM patients presenting at the Government Polyclinic (primary health care centre). This study is part of a project on outpatient diabetic care in Singapore. It was found that 23.7% of the subjects had no education and 51.3% had only primary school education. More than eighty percent of the subjects understood the importance of diet control and weight control in their condition. More than half of the subjects, 61% of males and 52.7% of females were aware that diabetes could not be cured and that once diabetes is controlled, that medication cannot be stopped and that one must still take the medication even if one feels well. Less than 30% knew about the interpretation of blood and urine sugar findings. The two major concerns amongst the subjects were complications and the need for long-term medication. These findings will be incorporated into the next phase of the project where a health education programme for NIDDM patients will be developed and evaluated. PMID- 1855437 TI - Insulin absorption is faster when keeping the infusion site in use for three days during continuous subcutaneous insulin infusion. AB - To evaluate the possible influence of regular infusion site changes on insulin absorption, fifteen type 1 diabetic patients using continuous subcutaneous insulin infusion (CSII) were studied on four occasions: the first day after an infusion site was settled, again the first day after a new infusion site was utilized and the two fourth days after the two infusion sites had been used for three days. A bolus of insulin (1 U/10 kg of body weight) was infused by the pump in the lower para-umbilical region. Plasma free insulin and blood glucose levels were determined before and during 240 min of the study at 30-min intervals. It was found that the peak times extracted from the individual insulin curves were shorter in 17 out of 23 curves when the fourth day was compared with the first day and the mean value of peak time of the fourth day was significantly shorter than that of the first day (56 +/- 11 vs 110 +/- 15 min, P less than 0.01). The mean area under the insulin curves during the first hour of the study tended to increase on the fourth day compared to that of the first day (25 +/- 2.2 vs 21 +/ 2.1 mU.l-1.min, P = 0.12). The decremental area of blood glucose on the fourth day was larger than on the first day (405 +/- 111 vs 82 +/- 160 mmol.l-1.min, P less than 0.05). We conclude that during CSII, the absorption rate of the injected insulin bolus is faster when the infusion site has been in use continuously for three days. PMID- 1855438 TI - The Thermocross: a simple tool for rapid assessment of thermal sensation thresholds. AB - We have developed the Thermocross, a simple device for rapid assessment of thermal sensitivity, tested it on healthy subjects and diabetic patients and evaluated its use in identifying patients whose sensation loss may expose them to the risk of neuropathic foot injury. Thermal discrimination deteriorated with age (P less than 0.001) in healthy subjects, but all the controls could detect a temperature difference less than or equal to 10 degrees C. In diabetic patients, the deficit in thermal sensation detected by the Thermocross paralleled the decline of nerve conduction. Thermocross thermal sensation was impaired in 87% of 38 ulcerated feet of 26 diabetic patients. We conclude that the Thermocross is a suitable tool for screening for sensation loss and that diabetic patients with impaired thermal sensation are vulnerable to ulceration. The Thermocross could also serve a useful educational purpose, the implications of reduced thermal sensation probably being more meaningful to patients and health care personnel than those of a reduction in the traditionally tested vibration sensation. PMID- 1855439 TI - Possible mechanism of proteolysis for the extrapancreatic action of tolbutamide. AB - In order to assess the mode of the extrapancreatic action of the sulfonylureas, we evaluated the contribution of a proteolytic mechanism for sulfonylurea action by analyzing the effects of a protease inhibitor on insulin- or tolbutamide stimulated liver fructose-2,6-bisphosphate (F-2,6-P2) formation using isolated rat hepatocytes. The F-2,6-P2 level in hepatocytes was significantly increased by the addition of insulin or tolbutamide. The stimulatory effect of insulin on the F-2,6-P2 formation was most significant when its level was reduced by the addition of 2 microM of forskolin. Insulin action on F-2,6-P2 formation was inhibited by the addition of a protease inhibitor, p-tosyl-L-arginine methyl ester hydrochloride (TAME). Tolbutamide (2 mM) significantly increased hepatocyte F-2,6-P2 level (P less than 0.01 vs the control level). In the presence of TAME, the stimulatory effect of tolbutamide was also suppressed. The present data suggest that a proteolytic mechanism is important in both insulin and tolbutamide action on the F-2,6-P2 formation, and it may be hypothesized that, like insulin, the chemical mediator of tolbutamide action is formed proteolytically. PMID- 1855440 TI - Continuous subcutaneous insulin infusion (CSII) and insulin antibodies in rabbits. AB - Using prepubertal male New Zealand White rabbits, continuous subcutaneous insulin infusion (CSII), delivered by either an external or an implantable infusion device, resulted in significantly higher insulin antibody (I-Ab) production than bolus injection (BII). We tested the influence during CSII of (1) the insulin species, (2) the insulin diluent, (3) the materials of which the infusion devices were made and (4) the incubation of insulin in a syringe on the backs of rabbits ('sham-infusion'), with the following results: (1) beef and sulphated beef insulins produced high levels of I-Abs, while porcine and human insulins produced moderate levels; (2) with all insulins used, 0.9% NaCl and 0.9% NaCl with 24-26 mmol NaHCO3 added, produced high levels of I-Ab. A buffer containing 0.7% NaCl, 0.136% sodium acetate trihydrate and 0.1% methyl-p-hydroxybenzoate and a buffer containing 16 mg/ml glycerol and 2 mg/ml phenol, produced highly significantly lower I-Abs (P less than 0.001); (3) insulin glass syringes produced much lower I Ab levels than in standard polypropylene syringes and (4) polypropylene syringes in a 'sham-infusion' technique, resulted in intermediate levels of insulin antibodies [(P less than 0.02) vs CSII; (P less than 0.005) vs BII]. Our data suggest that insulin immunogenicity is influenced by all four factors tested. We suggest that benefits of CSII therapy may be attenuated unless a best possible control of these factors is achieved. PMID- 1855441 TI - [Additional sacculi in the orifice of the cheek pouches of Campbell's hamster (Phodopus campbelli Thomas, 1905; Cricetidae, Rodentia)]. PMID- 1855442 TI - [Control over the spatial organization of liquid DNA crystals by using polyelectrolytes]. PMID- 1855443 TI - [A comparative study of the effect of H-2K restricted macrophage factor and of isolated H-2K k antigens on the expression of phenotypic markers and interleukin 2 production by syngeneic thymocytes]. PMID- 1855444 TI - [HIV-associated lymphomas]. AB - Forty-one HIV-positive homosexual men (mean age 39.8 [23-72] years) with malignant lymphomas were examined with the object of exploring the clinical and pathological spectrum of HIV-associated lymphomas in Central Europe, and their therapeutic aspects. There were 33 patients with non-Hodgkin lymphoma of high malignancy and four with non-Hodgkin lymphoma of low malignancy; four further patients suffered from Hodgkin's disease. 27 patients died during the period of observation. The mean survival period after diagnosis was 5.5 months. It depended on the stage reached by the lymphoma at the time of diagnosis: 11.8 months in stage I, 10.6 months in stage II, 7 months in stage III, 3.3 months in stage IV and 1.3 months in patients with primary involvement of the central nervous system by the lymphoma. Eight out of nine patients with highly malignant non-Hodgkin lymphoma in stage I or II attained complete and lasting remissions after chemotherapy or irradiation. However, only minimal prolongation of life was achieved in the 16 patients with lymphomas in stages III or IV. The response rate among all patients treated (complete and partial remissions) was 75%; 45% achieved complete remission. Hodgkin's disease responded well to standard therapy, but the disease rapidly recurred in every case. PMID- 1855446 TI - [Adjuvant therapy in colonic carcinoma]. PMID- 1855445 TI - [A iatrogenic arteriovenous fistula following laminectomy. A rare differential diagnosis of heart failure]. AB - An abdominal murmur was first heard in a now 46-year-old man four years after laminectomy at the age of 21. Signs of right heart failure and, ultimately, of global heart failure developed progressively and increasingly 20 years later. Echocardiography demonstrated enlargement of the right heart cavities, and atrial fibrillation was diagnosed. Cardiac catheterization revealed the typical picture of high output failure (cardiac output 13.9 l/min). Intra-arterial subtraction angiography demonstrated a fistula between the left iliac artery and vein. After operative closure of the fistula the signs of heart failure disappeared. Six months later a residual but insignificant fistula was still present, as well as persistent atrial fibrillation. Medical treatment having failed cardioversion successfully re-established sinus rhythm and the patient became symptom-free. Arteriovenous fistula after laminectomy is a rare cause of heart failure and often diagnosed very late. The prognosis is good once the fistula has been closed. PMID- 1855447 TI - [The determination of the compensation fee for medical college teachers. The judgement of the Sigmaringen Administrative Court of 28 Feb 1991]. PMID- 1855448 TI - [Cobalt exposure during the grinding of hard metals]. PMID- 1855449 TI - [The helper syndrome]. PMID- 1855450 TI - [Anti-arrhythmia agents following a myocardial infarct: the results of the CAST study. Cardiac Arrhythmia Suppression Trial]. PMID- 1855451 TI - Insulin acutely suppresses parathyroid hormone second messenger generation in UMR 106-01 osteoblast-like cells: differential effects on phospholipase C and adenylate cyclase activation. AB - Insulin modifies the effects of PTH on osteoblast-like cells. However, the basis for this effect is unknown. In bone and kidney cells, the effects of PTH on cellular function are mediated by second messengers generated through both the phospholipase C and adenylate cyclase systems. Therefore, we examined the effects of insulin on PTH second messenger generation in UMR-106-01 rat osteoblastic osteosarcoma cells. PTH produced a rapid, transient increase in intracellular free calcium concentration ([Ca2+]i) which was maximal at 30 sec and was only minimally reduced in the absence of extracellular calcium. Inositol-triphosphate (IP3) production was increased in parallel. PTH stimulation of [Ca2+]i was concentration-dependent from 0.5-1,000 nM, with half-maximal stimulation at approximately 50 nM PTH. A 30-sec exposure to 50 nM PTH produced 32% and 23% increases in IP1 and IP3 production, respectively (both P less than 0.05). Although insulin alone did not significantly alter basal [Ca2+]i, a 1-min exposure to 1-100 nM insulin produced a concentration-dependent suppression of the PTH-stimulated transient increase in [Ca2+]i and IP3 generation. 100 nM insulin decreased 50 nM PTH stimulation of [Ca2+]i and IP3 levels by 84% (P less than 0.02) and 80% (P less than 0.001), respectively. Preexposure to insulin also decreased PTH stimulation of intracellular cAMP levels, but to a lesser degree. A 1-min exposure to 100 nM insulin produced a 32% (P less than 0.01) decrease in PTH-stimulated cAMP generation, but lower insulin concentrations were without significant effects. These results demonstrate that in UMR-106-01 cells, insulin suppresses PTH stimulation of second messengers generated through both the phospholipase C and adenylate cyclase systems, but has a more marked effect on the former. PMID- 1855452 TI - Photoaffinity labeling of rat type I iodothyronine deiodinase. AB - The photoreactive compound p-nitrophenyl-2-diazo-3,3,3-trifluoropropionate (PAL) was coupled to [125I]rT3, T4, or T3 and incubated with liver and kidney microsomes of hypo-, hyper-, or euthyroid rats to identify the type I iodothyronine deiodinase. Various substrates or inhibitors of the enzyme, including rT3, T4, T3, 6-n-propylthiouracil (PTU), and iopanoic acid, were used as competitors to establish the specificity of protein labeling. The PAL derivatization enhanced the behavior of T4 and T3 as substrates for the type I enzyme. No specific labeling of microsomal proteins was observed with either rT3 or T4-PAL, presumably due to deiodination of the labeled compound. In contrast, T3-PAL labeled a 27-kDa band, the presence of which paralleled thyroid status. The labeling of only this protein was blocked by either substrates or enzyme inhibitors in a dose-dependent fashion, with a rank order of potency predicted by the activity of such compounds in type I enzyme assays. The specific nature of these competitions provides further evidence that this 27-kDa protein, identified in previous studies using N-bromoacetyl [125I]T3 or -T4, contains the active site of the rat type I deiodinase. This is in agreement with the mol wt of the rat type I deiodinase deduced from the recently identified cDNA coding for this protein. PMID- 1855453 TI - Effects of gonadal steroids on the ultrastructure of GnRH neurons in the rhesus monkey: synaptic input and glial apposition. AB - The secretion of the gonadotropins is modulated by the gonadal steroids, but the means by which these effects are mediated are not well understood. The present anatomical study was undertaken to investigate the possibility that the GnRH system responds to alterations in the gonadal steroid environment with reversible changes in synaptic input and glial wrapping such as have been observed in other neuroendocrine systems. The ultrastructure of GnRH neurons was studied in the preoptic area and medial basal hypothalamus of rhesus monkeys in various steroid conditions including five intact cycling, four long-term ovariectomized animals, two long-term ovariectomized animals with steroid replacement (LtOVX+), and two animals replaced with steroid at the time of ovariectomy (StOVX+). Electron micrographic montages of GnRH neuronal profiles were analyzed using computerized morphometrics, and the percentages of the length of perikaryal membrane immediately apposed by glial processes and that with postsynaptic modification were calculated. Ovariectomy resulted in a significant increase in the apposition of glial processes to GnRH perikaryal membranes and a significant decrease in their innervation in both brain regions. There was also a higher incidence of GnRH neurons with immunostaining confined to secretory granules and a decrease in the volume of nucleoli, both of which could be interpreted as indications that GnRH peptide synthesis was reduced in ovariectomized animals. After an ovarian steroid replacement regimen which mimicked two menstrual cycles, the innervation of GnRH neurons was increased and the glial ensheathment was partially reduced. This was true for both the LtOVX+ and StOVX+ steroid-replacement groups. GnRH neurons in the medial basal hypothalamus received more synaptic input than did those in the preoptic area, regardless of the steroid condition of the animal. The degree of glial ensheathment of GnRH neurons in the preoptic area became significantly greater than that in the medial basal hypothalamus after ovariectomy. These observations suggest there may be differences in the role of GnRH neurons in these two brain regions. These immunocytochemical ultrastructural studies provide strong evidence that alterations in the gonadal steroid milieu can produce morphological changes in the GnRH neuron and its immediate environment in the primate. PMID- 1855454 TI - C-type natriuretic peptide (CNP) in rats and humans. AB - We have established a specific radioimmunoassay (RIA) for C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, and have elucidated its tissue distribution and molecular form. In rats, high concentrations of CNP-like immunoreactivity (-LI) were detected in the anterior lobe (19.8 +/- 8.6 pmol/g) and neurointermediate lobe (4.64 +/- 0.74 pmol/g) of the pituitary gland. CNP-LI was present throughout the brain with its high concentrations in the hypothalamus and cerebellum. Small amounts of CNP-LI were also detected in the lower part of gastrointestinal tract and the kidney. However, no significant amount of CNP-LI was present in other organs including the heart. Considerable amounts of CNP-LI were detected throughout the human brain. High performance-gel permeation chromatography coupled with the RIA detected two peaks of CNP-LI in the rat brain; CNP and presumably its N terminally elongated form with 53 amino-acid residues, CNP-53. These findings indicate that the tissue distribution and processing pattern of CNP are clearly different from those of atrial natriuretic peptide and brain natriuretic peptide and suggest possible roles of CNP as a neurotransmitter or neuromodulator rather than as a cardiac hormone. PMID- 1855455 TI - Differentiated metabolic stimulation of rat pituitary lobes by peripheral and central endothelin-1. AB - Intravenous infusion (14 nmol/min) and lateral cerebral ventricular injection (9 pmol) of endothelin-1 increased rates of glucose utilization (quantitative autoradiographic [14C]deoxyglucose method) by 75-219% in pars intermedia and distalis of the rat pituitary gland. In rats given intraventricular endothelin, glucose metabolism was also increased significantly in pars nervosa (+92%). Metabolic activation by central endothelin in pars intermedia and distalis was inhibited by intraventricular pretreatment with the dihydropyridine, nimodipine, indicating that endothelin stimulates energy metabolism and probably hormone secretion in melanotrophs and pars distalis cells via L-type calcium channels. PMID- 1855456 TI - Ultrastructural evidence for cortico-chromaffin hybrid cells in rat adrenals? AB - The adrenals of perfusion fixed rats were investigated by electron microscopy. In 2 out of 12 animals studied, chromaffin cells were detected that contained organelles identical to adrenocortical mitochondria and smooth endoplasmic reticulum. The mitochondria were round-shaped with the vesicular cristae typical for steroid hormone producing cells. They were located within the cytoplasm of adrenomedullary cells neighbouring chromaffin vesicles, rough endoplasmic reticulum and the characteristic elongated mitochondria of chromaffin cells with laminar cristae. The mitochondria-like structures could be clearly differentiated from the extracellularly located synaptic endings. It can therefore be concluded that some rare cortico-chromaffin hybrid cells or chromaffin cells that present a mitochondrial-endoplasmic system of adrenocortical cells exist within the adrenal medulla. This surprising finding may offer an explanation for the long line of inconsistencies in clinico-pathological reports of adrenal morphology. PMID- 1855457 TI - Neonatal gonocytes co-cultured with Sertoli cells on a laminin-containing matrix resume mitosis and elongate. AB - We co-cultured gonocytes and Sertoli cells isolated on the day of birth and observed the appearance, 1 and 3 days after the start of culture, of gonocytes that had developed cellular processes and that were labeled by [3H]thymidine, respectively. These events occurred in the absence of hormones, etc. and with a time course very similar to that seen in vivo. In other incubations, we found that the presence of laminin in the underlying substrate was critical in promoting proliferation and elongation of gonocytes. These observations strongly suggest that interactions between gonocytes and other testicular cells/factors in the co-cultures promote maturation of these germ cells in vitro, and thus provide new evidence to support the concept that paracrine mechanisms are important during testicular development as well as in adults. PMID- 1855458 TI - Remembrances of the Meadowbrook conferences--when steroids came to DNA. PMID- 1855459 TI - Remembrances of contributions of Philip Smith and Bernardo Houssay to the development of neuroendocrinology. PMID- 1855460 TI - Glycoprotein hormones were always composed of subunits--we just had to find out the hard way. PMID- 1855461 TI - Cyclic changes in follistatin messenger ribonucleic acid and its protein in the rat ovary during the estrous cycle. AB - The purpose of this research was to characterize the localization of follistatin mRNA and protein in the adult rat ovary during the 4-day estrous cycle. Analysis of ovarian sections using in situ hybridization and immunohistochemistry demonstrated the presence of follistatin messenger RNA (mRNA) and its protein in granulosa and luteal cells; no follistatin (message or protein) was detected in any of the other ovarian cell types. An important observation was that the intensity of follistatin signals changed during granulosa differentiation and the estrous cycle. During folliculogenesis, the first detectable hybridization signal appeared in the granulosa cells of secondary follicles, but the signal was weak. However, when a preantral follicle reached the early tertiary stage (beginning antrum formation), the message signal was very strong, being expressed in all granulosa cells of all such follicles (300-400 microns in diameter). In atretic follicles, follistatin mRNA was localized to granulosa cells, but only during the early stages. The above hybridization pattern of follistatin mRNA in prenatral and atretic follicles appeared constant throughout the estrous cycle. Interestingly, immunohistochemistry studies showed that the follistatin protein was detected only in certain follicles, being restricted to those which were healthy. On the morning of estrus, the follistatin protein was localized to a subpopulation of early tertiary follicles, presumably the dominant follicles selected to ovulate in the next cycle. As the dominant preovulatory follicles matured through diestrus and proestrus, the follistatin mRNA and protein signals appeared more intense in the granulosa cells. After ovulation, the hybridization and immunohistochemical signals continued to be strong in the newly formed corpora lutea on estrus morning. After luteolysis on diestrus-I, neither the follistatin message nor the protein was detectable in the corpora lutea. In conclusion, these results suggest that the follistatin message is present in all the granulosa cells of every developing follicle throughout the estrous cycle, but the follistatin protein appears to be present in only the selected dominant follicles. Accordingly, the possibility that follistatin might be an important regulatory molecule for selection/atresia should be considered. PMID- 1855462 TI - Inhibition of suckling-induced prolactin release by dexamethasone. AB - The effect of dexamethasone (DEX) treatment (400 and 200 micrograms/kg BW 21 and 2 h before suckling stimulus, respectively) on suckling- and domperidone (DOMP) induced PRL release was investigated in freely moving, primiparous lactating rats. DEX completely blocked suckling-induced plasma PRL release without affecting DOMP-induced release of the hormone suggesting a central action of DEX. The effect was transient because it could not be detected on the second day of testing. The effect of DEX implanted in three different brain areas on suckling- and DOMP-induced PRL release was also tested. Implants surrounding the hypothalamic paraventricular nuclei and dorsal hippocampus failed to affect PRL release induced by suckling stimulus. Surprisingly, DEX suppressed PRL release induced by suckling stimulus when it was implanted into the medial basal hypothalamus. These findings demonstrate that DEX is a potent inhibitor of the suckling-induced PRL release. They also indicate that the site of action of DEX is not at the anterior pituitary gland or the paraventricular nuclei and hippocampus because DEX treatment and DEX implants had no effect on plasma PRL levels induced by DOMP and suckling stimulus, respectively. Our data suggest that the effect of DEX is mediated through a region of the medial basal hypothalamus. The observed transient block in suckling-induced PRL release may be physiologically relevant during stress in lactating mothers for conserving pituitary stores of the hormone needed for milk production or being able to adapt to a rapid change in osmoregulation. PMID- 1855463 TI - Regulation of proenkephalin A messenger ribonucleic acid levels in normal B lymphocytes: specific inhibition by glucocorticoid hormones and superinduction by cycloheximide. AB - Proenkephalin A (PEA) encodes a group of small peptides known to function as neurotransmitters, neuromodulators, and neurohormones in the nervous and neuroendocrine systems. This gene has been shown to be expressed in lymphoid cells, supporting the concept of bidirectional communication between the immune system and the central nervous system. In the present study, we investigated the effect of steroids and the inhibition of protein and RNA syntheses on the regulation of PEA expression in normal rat B cells. The transient expression of PEA messenger (m) RNA levels occurring normally in B cells was markedly inhibited by the presence of either 50 nM prednisolone or dexamethasone, both of which are glucocorticoids; other steroids, such as testosterone or the steroid-inactive metabolite androsterone, were ineffective. In the presence of cycloheximide, a protein synthesis inhibitor, PEA mRNA was superinduced by a factor of 15-fold. Sorting by flow cytometry of cycloheximide-treated cells followed by in situ hybridization analysis revealed that the expression of PEA mRNA was exclusively confined to a small fraction of B cells. These results indicate that the mechanisms regulating PEA gene expression in B cells differ from those previously described in cells of the neuroendocrine and the nervous systems. PMID- 1855464 TI - Adrenocorticotropin-releasing factor down-regulates glucocorticoid receptor expression in mouse corticotrope tumor cells via an adenylate cyclase-dependent mechanism. AB - Anterior pituitary POMC transcription and peptide release are negatively regulated by glucocorticoids and stimulated by CRF. Although pretreatment of corticotrope cells with CRF markedly inhibits subsequent glucocorticoid effects, the mechanism of this action is unclear. We have thus used a mouse corticotrope tumor (AtT20) cell line, to examine the effects of CRF on glucocorticoid receptor (GR) messenger RNA levels and on GR capacity/nuclear translocation. GR mRNA levels were measured by solution hybridization/S1 nuclease protection, and both total cell binding and nuclear binding were determined with [3H]dexamethasone ([3H]DEX). CRF treatment of AtT20 cells led to a rapid time-dependent decrease in GR mRNA levels which preceded a dose- and time-dependent decrease in GR binding capacity. Scatchard analysis showed a single class of high affinity binding sites (GR) in both control and CRF-treated cultures, and a decrease in the total number of GR after CRF treatment. The relative proportion of nuclear vs. cytoplasmic localized [3H]DEX-bound GR did not differ between control and CRF-treated cultures, indicating that CRF does not interfere with GR nuclear translocation. To investigate whether CRF regulates GR expression through the adenylate cyclase system, as it does POMC, AtT20 cells were treated with either forskolin or 8 bromo-cAMP, and specific nuclear GR binding was determined. Both drugs mimic the CRF-induced decrease in GR binding, and in addition forskolin decreased GR mRNA levels; in contrast, forskolin had no effect on GH3 cell GR levels. These results suggest that CRF can decrease the cellular concentration of GR, and thus potentially the response to glucocorticoids, through the same mechanism by which it stimulates anterior pituitary POMC expression. PMID- 1855465 TI - Photoperiod associated changes in insulin-like growth factor-I in reindeer. AB - Insulin-like growth factor-I (IGF-I) concentrations were measured in the plasma of reindeer calves exposed to a manipulated photoperiod, indoors, of either 16 h light followed by 8 h dark each day (16L:8D) (n = 3) or 8L:16D (n = 3) from about the autumnal to the vernal equinox, to determine whether the seasonal growth spurt normally seen in spring is associated with a photoperiod-induced rise in IGF-I. A high quality concentrate diet was available ad libitum, and individual food intake was recorded daily. The animals were weighed, bled, and the diameters of their testes were measured every 2 weeks. Plasma samples were assayed for IGF I by RIA. Six to 8 weeks after the start of the study those calves exposed to 16L:8D showed a significant increase in plasma IGF-I concentration, which was maintained until the close 24 weeks after the start. In contrast, IGF-I plasma concentrations in those calves exposed to a day length of 8L:16D did not significantly alter during the study. The elevated IGF-I in the 16L:8D group was associated with rapid weight gain, higher food intake, and decreased testes size compared with the 8L:16D group. We have shown that the seasonal growth spurt is preceded by an elevation in plasma IGF-I concentration. Further, this elevation in IGF-I is day length dependent. This is the first account of any growth factor secretion being regulated by photoperiod. PMID- 1855466 TI - Analysis of the steroid binding domain of rat androgen-binding protein. AB - The site-directed photoaffinity ligand [3H]17 beta-hydroxy-4,6-androstadien-3-one (delta 6-testosterone) was used to label the steroid binding domain of rat androgen-binding protein (rABP). After digestion with trypsin, the major radiolabeled peptide was isolated by reverse phase chromatography. The peptide was found to have the following amino acid sequence: Ile Ala Leu Gly Gly Leu Leu Leu Pro Thr Ser. Gaps in the sequence that one would anticipate if delta 6 testosterone formed an adduct with a single amino acid were not encountered. Several different amino acids appear to have been labeled as expected given the free radical nature of photoactivated delta 6-testosterone. The sequence obtained corresponded to a tryptic peptide (amino acids 171-181) of the rABP precursor. The only other protein having this amino acid sequence was human sex hormone binding globulin. The binding domain lies in a hydrophobic pocket that contains a predicted beta-sheet and turn secondary structure, as would be anticipated given the hydrophobic nature of the steroid molecule. A hydropathy and secondary structure analysis of rABP was performed as a basis for discussing the results of the current study in relation to previous studies on the steroid binding domain on human sex hormone binding globulin. PMID- 1855467 TI - Regulation of the uteroferrin gene promoter in endometrial cells: interactions among estrogen, progesterone, and prolactin. AB - Expression of the gene for the porcine transplacental iron transport protein uteroferrin (UF) is largely restricted to the uterus, where it is differentially regulated by estrogen (E) and progesterone (P). To study the regulatory mechanisms subserving these effects, a 2-kilobase genomic fragment corresponding to -2005 to 48 nucleotides of the UF gene was ligated up-stream to the reporter gene chloramphenicol acetyltransferase (CAT). This construct (UF-CAT) was transiently transfected into rabbit endometrial (HRE-H9), mouse fibroblastic (AKR 2B), and human choriocarcinoma (JEG-3) cells. The basal gene promoter activity of UF-CAT was exhibited in H9 cells, but not in AKR-2B or JEG-3 cells. In contrast, a simian virus-40 early promoter (SV2) was functional in all three cell lines. The H9 cells were used to examine steroid regulation of the UF gene promoter. The CAT expression in H9 cells primed with E and PRL, but not with E or PRL alone, was stimulated by P. In contrast, basal activity of SV2 in these cells was unaffected by hormones, singly or in combination. To examine the basis for the E/PRL-dependent response to P, levels of P and E receptors in H9 cells were quantified. PRL and E plus PRL increased the number of high affinity sites for P, but had little effect on levels of high affinity sites for E in treated vs. untreated H9 cells. In vivo administration of PRL to cyclic gilts had no effect on levels of endometrial UF mRNA and secreted UF protein; however, E- plus PRL treated gilts had higher (P less than 0.05) levels of endometrial UF mRNA and luminal UF than PRL-treated gilts. These results demonstrate in vitro functional activity of the UF gene promoter and associated 5' flanking region and suggest that sequences within this region may mediate tissue-specific and steroid hormone regulated expression of the UF gene. Moreover, interactions among E, PRL, and P modulate UF gene expression in vivo and in vitro. PMID- 1855468 TI - Opposing effects of retinoic acid and dexamethasone on cellular retinol-binding protein ribonucleic acid levels in the rat. AB - Cellular retinol-binding protein (CRBP) is a potential mediator of vitamin A action. To determine whether retinoic acid and dexamethasone administration, alone and in combination, influence CRBP gene expression, adult female vitamin A sufficient Sprague-Dawley rats randomly received 1) all-trans retinoic acid (100 micrograms) by intragastric intubation, 2) dexamethasone (2 micrograms/g BW) by ip injection, or 3) both all-trans retinoic acid and dexamethasone in the same doses. Control animals received either cottonseed oil by intragastric intubation or saline by ip injection. Six hours after treatment, lung and liver tissue were collected for Northern blot analysis with the radiolabeled cDNA specific for rat CRBP. Retinoic acid administration increased the amount of lung CRBP mRNA only, whereas dexamethasone decreased both lung and liver CRBP mRNA abundance. In animals treated with both retinoic acid and dexamethasone, CRBP mRNA abundance was also reduced. We conclude that CRBP gene expression can be modulated by both retinoic acid and dexamethasone in the vitamin A-sufficient animal. In the whole animal, our findings indicate that dexamethasone not only represses CRBP gene expression, but also opposes the effect of retinoic acid. PMID- 1855469 TI - The effects of a brain-enhanced estradiol delivery system on testosterone and androgen-dependent tissues. I. Dose-response and time-course evaluation. AB - The primary objective underlying hormone treatment of prostatic adenocarcinoma is to induce an effective androgen deprivation, and high dose estrogen therapy is as effective as surgical castration in abolishing the growth-promoting effects of androgens on prostatic tissue. An estradiol-chemical delivery system (E2-CDS), with sustained release of E2 in the brain, may be potentially useful in the treatment of prostatic cancer by virtue of the need for lower or less frequent doses of the estrogen. In this study we evaluated the dose- and time-dependent effects of the E2-CDS vs. 17 beta-E2 on serum testosterone (T) and weights of androgen-dependent tissues in male rats. Rats received a single iv injection of E2-CDS (0.1, 0.5, or 1.0 mg/kg), equimolar doses of 17 beta-E2, or the drug's vehicle. Sera and tissues were collected 1, 7, 14, or 21 days later for determination of hormone levels and tissue weights. The E2-CDS exhibited a dose- and time-dependent suppression of serum T and weights of the ventral prostate and seminal vesicles. In contrast, 17 beta-E2 had no significant effect on serum T or growth of these androgen-dependent tissues. Serum T levels were significantly reduced by 98%, 82%, and 59% at 1, 7, and 14 days, respectively, with the 1.0 mg/kg dose of E2-CDS. The E2-CDS significantly reduced prostate weight by 45% and 50% (1.0- and 0.5-mg/kg doses, respectively) 7 days and by 27% (0.5 mg/kg dose) 14 days after treatment. Similarly, seminal vesicle weights were reduced by 14 20% on day 1, maximally reduced by 39-48% on day 7, and still reduced by 24-36% on day 14 compared with the control levels. Weights of these tissues returned to control levels by day 21. Serum E2 was elevated through 7 days by E2-CDS or on day 1 only by 17 beta-E2. PRL secretion was stimulated for 1 week by both forms of estrogen. Anterior pituitary weights were increased by the E2-CDS through 14 days, while 17 beta-E2 had no significant effect. These data indicate that the E2 CDS causes chronic suppression of serum T, which subsequently results in regression of androgen-dependent tissue weight. PMID- 1855470 TI - The effects of a brain-enhanced estradiol delivery system on testosterone and androgen-dependent tissues. II. The role of testosterone. AB - The present study was undertaken to evaluate the efficacy of an estradiol chemical delivery system (E2-CDS) for the brain vs. estradiol benzoate (E2-BNZ) in suppressing serum testosterone (T) and weights of the ventral prostate and seminal vesicle in male rats. Also, the role of serum T in the weight reduction of androgen-dependent tissues observed after E2-CDS treatment was further evaluated in these studies. Intact male rats received a single iv injection of either E2-CDS at a dose of 1.0 mg/kg or an equimolar dose of E2-BNZ (0.95 mg/kg). Sera and tissue samples were collected 1, 7, 14, or 21 days after injection for determination of hormones and tissue weights. A single injection of E2-CDS suppressed serum T levels by 96%, 83%, 46%, or 63% 1, 7, 14, or 21 days after treatment, respectively. In contrast, an equimolar dose of E2-BNZ had no significant effect on serum T at any sampling time examined. Prostate weight was maximally reduced by 53% at 7 days and remained significantly suppressed by more than 31% throughout the 21-day time course. Similarly, seminal vesicle weight was reduced by 14% on day 1, maximally reduced by 41% on day 7 and remained significantly suppressed through day 21. In contrast, E2-BNZ was ineffective in inducing weight changes in either of these tissues. Serum PRL was significantly elevated through day 14, while E2 was elevated through day 7 by E2-CDS. Both the anterior pituitary and adrenal gland weights were stimulated by E2-CDS treatment. Testis weight was moderately reduced by both esters. In a subsequent study serum T was reduced by 98% and 97% 1 and 7 days, respectively, after E2-CDS treatment, and weights of the ventral prostate and seminal vesicle were reduced by 47% and 40%, respectively, at 7 days. In contrast, in rats treated with Silastic capsules containing T, the expected E2-CDS-induced weight regression was prevented in both prostate and seminal vesicles. These data indicate that the prolonged effects of E2-CDS on weights of androgen-dependent tissues are caused by its ability to produce profound suppression of the serum T concentration. PMID- 1855471 TI - Molecular heterogeneity and cellular localization of carboxypeptidase H in the islets of Langerhans. AB - The intracellular distribution and molecular heterogeneity of carboxypeptidase H was studied in rat insulinoma tissue and isolated islets of Langerhans by a combination of immunohistochemical, ultrastructural, subcellular fractionation, and immunoblotting analyses. Immunofluorescence microscopy of islets demonstrated the presence of carboxypeptidase H in both insulin-containing B cells and glucagon-containing A cells. Quantitative ultrastructural analyses of islet B cells indicated that the enzyme was concentrated in mature insulin secretory granules, clathrin-coated condensing granules, and to a lesser extent the Golgi apparatus. Carboxypeptidase H activity was localized principally to secretory granule subfractions of insulinoma tissue, where it was present for the major part (70%) as a form which is readily solubilizable at pH values prevailing in the granule interior (5.5). This species migrated as a diffuse band of 53-57 kilodaltons (kDa) on immunoblot analysis using antisera raised against the purified native enzyme. In contrast, the insoluble form which was associated with the granule membrane at pH 5.5, migrated as a relatively compact band of 55-57 kDa. Carboxypeptidase H activity was also present in subcellular fractions which contained Golgi membranes together with elements of the endoplasmic reticulum, and in a low density secretory granule fraction which may represent immature granules. The enzyme in these compartments, like the granule membrane species, migrated as a compact 55-57 kDa band on immunoblots. Two-dimensional electrophoretic immunoblot analysis of secretory granules suggested that both membrane and soluble forms of the enzyme were glycoproteins and that the terminal glycosylation was similar in both instances. Antiserum raised against the deduced C-terminal 11 amino acids of the cloned carboxypeptidase H sequence recognized the 55-57 kDa membrane component in granules but did not react with the 53-57 kDa soluble species. A major difference between the soluble and membrane forms therefore appears to be a structural modification or proteolytic removal of the C terminal domain in the trans-Golgi or early secretory granule compartment. The concept that proteolysis is involved is further supported by the observation that the relative proportion of the high and low mol wt forms of the enzyme in different subcellular fractions correlated with that of proinsulin and insulin, respectively. The membrane association of the 55-57 kDa form of carboxypeptidase H is disrupted at pH values of 9 and is dependent on ionic strength. This further suggests that the C-terminus of the protein may have an important role in the sorting or concentration of the enzyme in vesicular elements of the regulated pathway of secretion. PMID- 1855472 TI - Restoration of pulsatile luteinizing hormone secretion after fasting in rhesus monkeys (Macaca mulatta): dependence on size of the refeed meal. AB - In men and adult male rhesus monkeys brief periods of fasting (i.e. 1-2 days) can often lead to a suppression of hypothalamic-pituitary-testicular axis activity, marked by decreased circulating concentrations of LH, FSH, and testosterone. Refeeding a normal meal can rapidly restore normal secretory patterns of LH and testosterone. To learn more about the nature of the signal that links reproductive hormone secretion to nutrient intake, we examined whether the degree of restoration of pulsatile LH and testosterone secretion after a brief period of fasting is influenced by the size of the refeed meal. Adult male rhesus monkeys had indwelling venous catheters surgically implanted and were maintained on swivel/tether systems for remote collection of blood samples. Monkeys were fasted for 1 day and then on the following day they were refed one of five meals which varied in size and calorie content (i.e. 0 Cal/0 pellets Purina monkey chow; 100 Cal/5 pellets; 200 Cal/10 pellets; 300 Cal/15 pellets; or 600 Cal/30 pellets). Blood samples were collected from 0800-2400 h at 20-min intervals on the days of refeeding and assayed for LH and testosterone content. After a day of fasting, the frequency of pulsatile LH secretion the following morning was very low (0.56 +/- 0.1 pulses/3 h, measured from 0800-1100 h). When monkeys were not refed (i.e. were subjected to a second day of fasting; 0 pellet group) LH pulse frequency remained low [2.88 +/- 0.72 pulses/13 h, measured from 1100-2400 h (equivalent to 0.66 pulses/3 h)] throughout the day and evening hours. Refeeding monkeys 5, 10, 15, and 30 pellets caused a progressive stimulation of pulsatile LH secretion (3.17 +/- 0.54, 3.67 +/- 0.56, 5.5 +/- 0.67, and 6.38 +/- 0.53 pulses/13 h, respectively). Like LH pulse frequency, mean circulating LH and testosterone concentrations progressively increased as the size of the refeed meal was increased. For all three parameters (i.e. LH pulse frequency, mean LH concentration, and mean testosterone concentration) there was a significant, P less than or equal to 0.001, linear trend with increasing meal size. These findings indicate a very strong relation between the level of nutritional intake and the level of central drive to the reproductive axis during nutritional recovery from fasting, and suggest a physiological parameter that responds in a progressive fashion to increasing food intake serves as the signal to link central drive to the reproductive axis to changes in nutrient intake.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1855473 TI - Ontogeny of parathyroid hormone-related protein in the ovine parathyroid gland. AB - PTH-related protein (PTHrP) has been implicated in calcium regulation during fetal life. In this study the ontogeny of PTHrP was examined in ovine parathyroid glands. Immunohistochemical techniques, Western blot analysis, and a RIA with antisera raised against synthetic fragments of human (h) PTHrP (i.e. 1-34, 1-40, 50-69, and 107-141) were used to detect the presence of immunoreactive PTHrP in parathyroid glands from fetal and neonatal lambs and maternal ewes. Positive immunostaining for PTHrP was observed in fetal (from 116 days of gestation) and lamb (up to 180 days post birth) but not maternal parathyroid glands with the PTHrP(50-69) antiserum. Fetal and lamb parathyroid glands consisted entirely of one cell type in which PTHrP immunoreactivity to PTHrP(50-69) antiserum was found. In contrast, immunoreactivity to PTHrP could not be detected in sections of fetal, lamb, or maternal parathyroid glands with antisera raised against PTHrP(1-34) or PTHrP(107-141). However, PTHrP immunoreactivity in urea/acid extracts of newborn lamb parathyroid glands could be detected by Western blot analysis and RIA with antisera raised against the N-terminal portion of PTHrP. Western blot analysis with the PTHrP(1-34) antisera revealed that urea/acid extracts of newborn lamb parathyroid glands contained a substance with a mol wt of 14.4K, which corresponded in size to that of hPTHrP(1-84). Newborn lamb parathyroid glands contained 0.35 ng PTHrP/micrograms extract, whereas maternal parathyroid glands contained only 0.035 ng PTHrP/micrograms extract when tested in a RIA employing recombinant hPTHrP(1-84) as standard and an antibody raised against hPTHrP(1-40). The detection of immunoreactive PTHrP in the developing ovine parathyroid gland provides further evidence to support the suggestion that PTHrP produced in the parathyroid gland is involved in the normal hormonal regulation of calcium metabolism in the mammalian fetus and neonate. PMID- 1855474 TI - Antiprogesterone, RU 486, facilitates parturition in cattle. AB - RU 486, a potent progesterone antagonist with high affinity for progesterone receptor, was used alone or in combination with relaxin in late pregnant cattle to determine its effect on induction of parturition. Cross-bred beef cattle were bred by artificial insemination. An indwelling cannula was inserted into a jugular vein on day 269 (expected term = day 283) for repeated blood sample collection. On day 277, the cattle were assigned randomly to three groups (n = 6 each): group 1 received RU 486 (2 mg/kg BW, im) at 0800 h on days 277 and 278; group 2 received the same RU 486 treatment plus 3000 U relaxin, injected sc at 0800 h on day 278; and group 3 served as controls and received vehicle injection. Parturition occurred 55 h after treatment in group 1 and 53 h after treatment in group 2 compared with 210 h in the controls (P less than 0.01). The calves from treated groups were vigorous at birth, and their birth weights (32 and 33 kg in groups 1 and 2) were less than those of control calves (38 kg; P less than 0.01). There was no incidence of difficult birth (dystocia) with RU 486 treatment compared with that in the controls. Placenta delivery averaged 6.5 h after birth in both RU 486-treated groups and did not differ from the control value (5 h). Plasma progesterone concentrations averaged 8.2 ng/ml during the pretreatment period for all animals. Progesterone started to decrease markedly by 1200 h on day 278, dropped to about 4 ng/ml by 2400 h that same day, and was at basal levels on day 279, the day of calving, in two hormone-treated groups. In sharp contrast, progesterone was maintained at about 6 ng/ml in placebo-treated controls during this period and did not decrease to basal levels until 2 days before parturition on day 286 (P less than 0.01). Peak RU 486 in plasma was 7.2 ng/ml after the first injection and 14.3 ng/ml after the second injection, and averaged 7.9 ng/ml on the day of induced calving (day 279). Peak relaxin was 4.1 ng/ml after hormone injection. The results indicate that RU 486 alone or combined with relaxin precisely controlled the time of parturition in cattle in late pregnancy. Such treatment can be used to facilitate parturition and increase survival rates of neonatal calves without detrimental effects of dystocia, retention of placenta, and delayed postpartum fertility. PMID- 1855475 TI - High fat feeding causes insulin resistance and a marked decrease in the expression of glucose transporters (Glut 4) in fat cells of rats. AB - With the identification of two different glucose transporter species in adipose cells it is crucial to determine the role of these transporters in the alterations in glucose transport activity associated with different metabolic and nutritional states. In the present study we assess levels of expression of Glut 1 and Glut 4 transporters and basal and insulin-stimulated glucose transport activity in adipocytes from Sprague-Dawley rats fed standard chow (control), combined liquid diet and standard chow (overfed), high fat diet, or energy restricted diet for 7 weeks. High fat feeding was associated with relative postprandial hypoglycemia (P less than 0.05) and hypoinsulinemia (P less than 0.05). Although the high fat fed animals had lower body weights (P less than 0.05) than control rats, their body compositions showed obesity, with 36% heavier epididymal fat pads (P less than 0.05) and a 47% increase in adipocyte volume (P less than 0.05). Fat feeding caused a 78% reduction in insulin-stimulated glucose transport per adipocyte (P less than 0.05). In parallel we found 92% and 94% reductions in Glut 4 protein and mRNA per adipocyte, respectively, (P less than 0.01) in fat-fed rats. Substantial reductions were also seen in Glut 1 protein and mRNA per fat cell in the same rats (62% and 76%, respectively; P less than 0.05). However, the changes in Glut 1 expression were of the same magnitude as changes in the cytoskeletal protein beta-actin, reflecting a decreased expression of several proteins in this nutritional state. Even though overfeeding and energy restriction brought about opposite changes in adiposity, no significant alterations were demonstrated in glucose transport rate or glucose transporter expression. The impaired insulin-stimulated glucose transport in adipose cells from high fat-fed rats occurs in the presence of a dramatic decrease in the expression of the major insulin-responsive glucose transporter (Glut 4). The reduced gene expression may be caused by chronic hypoinsulinemia and may contribute to the insulin resistance observed in this state. PMID- 1855476 TI - Expression of the neural cell adhesion molecule in endocrine cells of the ovary. AB - In the adult mammalian ovary morphogenesis and differentiation processes are under hormonal control and, thus, occur in a highly regulated way during the sexual cycle. Cell-cell interactions, such as cell adhesion and cell separation, are crucial during these events. Here we show that the ovarian endocrine cells, which are prototypes of steroid-producing cells, express neural cell adhesion molecules (NCAMs). The combined use of in situ hybridization histochemistry, immunocytochemistry at the light and electron microscope levels, S1 nuclease protection assays, and Western blotting revealed that in the ovary of the adult rat during the estrus cycle and pregnancy, NCAM mRNA and the 140-kDa isoform of this protein are expressed mainly in granulosa cells of growing preantral and antral follicles and in corpora lutea. Since the granulosa cells lining the forming antrum and the antral fluid were strongly immunoreactive, a role for NCAM in the formation of the follicular antrum is proposed. The expression of NCAM was also associated with luteal cells of the active corpus luteum, indicating a role for NCAM in the morphogenesis of this endocrine compartment. Moreover, thecal cells of large follicles and hypertrophic thecal cells of atretic follicles expressed NCAM, as did interstitial cells, which are derived from thecal cells of atretic follicles. We propose that the adhesion molecule, NCAM, is an important factor involved in the recognition and intercellular interaction of ovarian endocrine cells and, thus, participates in the regulation of the cyclic remodeling processes of the ovarian endocrine compartments. PMID- 1855477 TI - Potassium-stimulated angiotensin release from superfused adrenal capsules and enzymatically dispersed cells of the zona glomerulosa. AB - The cells of the adrenal cortex contain angiotensin-II (AII), but whether this peptide is synthesized there (vs. internalized from the systemic circulation), whether it is secreted, and whether it is important in aldosterone production remain uncertain. To address these issues, we studied AI and AII release from superfused rat adrenal capsules and dispersed glomerulosa cells. Superfused adrenal capsules released 7-fold more AII in 270 min than the capsules originally contained (495 +/- 101 fmol AII/rat released vs. 66 +/- 8 fmol AII/rat tissue content). The amount of AI released in the same period only slightly exceeded the tissue content. In response to higher potassium concentrations in the medium (9 vs. 3.6 mM K+), adrenal capsules and dispersed glomerulosa cells both released significantly more AI and AII into the superfusate. This release of AI and AII was oscillatory. The oscillations occurred in each of 15 experiments, with a period of 45-90 min. Decapsulated adrenal glands (the zona faciculata/reticularis plus medulla) also contained and released AII, but did not respond to potassium stimulation. There was a highly significant correlation between AII and aldosterone release. This was especially apparent if aldosterone secretion was examined during oscillations of AII release (r = 0.97; P less than 0.0001). We conclude that AII is synthesized in the zona glomerulosa and can be released in response to stimuli. The close correlation between AII and aldosterone secretion suggests that locally produced AII may play an important role in aldosterone biosynthesis. PMID- 1855478 TI - A novel vitamin D3 analog, 22-oxa-1,25-dihydroxyvitamin D3, inhibits the growth of human breast cancer in vitro and in vivo without causing hypercalcemia. AB - Although 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has been shown to inhibit the growth of certain malignant cells, its hypercalcemic effect has prevented clinical application. We have recently developed a novel vitamin D3 analog, 22 oxa-1,25-(OH)2D3 (OCT), that is capable of promoting differentiation and inhibiting proliferation without inducing hypercalcemia. The present study was undertaken to determine whether OCT could be applied for the treatment of breast cancer with or without estrogen receptor (ER). OCT inhibited the proliferation of both ER-positive (MCF-7, T-47D, and ZR-75-1) and ER-negative breast cancer cells (MDA-MB-231 and BT-20) in vitro in a time- and dose-dependent manner, as determined by cell number and [3H]thymidine uptake. The antiproliferative effect was observed with a concentration as low as 10(-11) M OCT, and treatment of MCF-7 cells with 10(-8) M OCT for 8 days caused more than a 50% reduction in cell number compared with that of vehicle-treated cells. OCT was approximately 1 order of magnitude more potent than 1,25-(OH)2D3 in inhibiting the proliferation of MCF 7 cells. The in vivo effect of OCT was examined in athymic mice implanted with ER negative MX-1 tumor, which was established as the xenograft derived from human breast carcinoma. Intratumor administration of OCT three times a week remarkably delayed the growth of MX-1 tumor in a time- and dose-dependent manner. The antitumor effect of 1 microgram/kg BW OCT was greater than that of 500 microgram/kg BW adriamycin, and the relative tumor weights in each group on day 26 were 29.7% and 50.5% of that in the vehicle-treated group, respectively. The effects of OCT and adriamycin were additive, and the relative tumor weight after 26 days of combined treatment was 21.7% of that in the vehicle-treated group. Oral administration of OCT was also effective, and the relative tumor weight in the OCT-treated group (1 microgram/kg BW) was 54.6 +/- 0.1% (mean +/- SEM) of that in the vehicle-treated group. Neither intratumor nor oral administration of OCT raised the serum calcium level in these animals. These results demonstrate that OCT is a potent inhibitor of the proliferation of breast cancer cells with or without ER and that OCT inhibits the growth of breast cancer in vivo without inducing hypercalcemia. We suggest that OCT may provide a new strategy for the treatment of breast carcinoma regardless of ER status. PMID- 1855479 TI - Effect of prostaglandin F2 alpha on cytosolic free calcium ion concentrations in rat luteal cells. AB - Changes in cytosolic free calcium concentrations [( Ca2+]i) in response to prostaglandin F2 alpha (PGF2 alpha) were measured in single rat luteal cells, using the calcium-sensitive fluorescent dye fura-2. A total of 112 cells were studied in 20 experiments. The average resting [Ca2+]i was 113 +/- 6.4 nM. In 59 cells (53%), there was a 4.6 +/- 0.2-fold increase in [Ca2+]i within 29.3 +/- 1.0 sec of PGF2 alpha administration, and the cells recovered by 78.0 +/- 4.5 sec. The magnitude of the increase in [Ca2+]i in response to PGF2 alpha was not changed by an increase in the concentration of PGF2 alpha. Perifusion with low calcium buffer reduced, then eliminated, the [Ca2+]i response to PGF2 alpha. Perifusion of cells with PGF2 alpha resulted in a single transient [Ca2+]i response, similar to that after short term exposure to PGF2 alpha. Many (67%) of the cells that responded to PGF2 alpha also responded to GnRH. No additive increase in [Ca2+]i was seen when PGF2 alpha and GnRH were administered together. The source of the calcium appears to be intracellular stores that are shared by GnRH and PGF2 alpha. PMID- 1855480 TI - The 16K fragment of prolactin specifically inhibits basal or fibroblast growth factor stimulated growth of capillary endothelial cells. AB - Intact 23 kilodalton (kDa), rat PRL is enzymatically cleaved in many target tissues to a 16 kDa (16K PRL) and an 8 kDa fragment. After reduction of an internal disulfide bond the fragments are released. 16K PRL was shown to be a potent mitogen on mammary epithelial cells via PRL receptors. Since estradiol induced prolactinomas develop a new blood supply we tested the action of intact PRL and 16K PRL on growth of new vessels (angiogenesis). The angiogenic action of intact PRL and 16K PRL was tested in cultured bovine brain and adrenal cortex endothelial cells. Basal (b) or b-fibroblast growth factor (FGF) stimulated growth was estimated by counting cells or measuring the level of incorporation of 3H-thymidine into DNA. Paradoxically, 16K PRL inhibited the basal and FGF stimulated growth of cultured endothelial cells in a dose-dependent fashion. Intact PRL or the cleaved but not reduced PRL were inactive even at a 100-fold higher concentration. When reformation of disulfide bonds was inhibited by carbamidomethylation of 16K PRL the preparations were more potent. 16K PRL had no effect on the mitogenic action of bFGF on baby hamster kidney cells which are known to have FGF receptors. These data demonstrate that in vitro 16K PRL is a potent and specific angiolytic factor, i.e. it inhibits angiogenesis. Furthermore, the action of 16K PRL does not appear to be via the known PRL or FGF receptors. Since angiogenesis is an essential component of tumor growth 16K PRL has potential as a therapeutic agent for the treatment of cancer. PMID- 1855481 TI - Purification and characterization of thyroid hormone-responsive rat hepatic proteins. AB - Bernal et al. identified two proteins in rat hepatic nuclear extract, t- and n proteins, that were enriched by thyroidectomy or T3 treatment, respectively. We purified these proteins, raised monospecific antibodies, and characterized them by Western blotting. Anti-n and anti-t-protein antibodies did not recognize t- and n-proteins, respectively. The n-protein was present in nuclear and cytosolic fractions, was present at low levels in the microsomal fraction, and was absent in the mitochondrial fraction of rat liver. The t-protein was more abundant in mitochondrial and microsomal fractions than in the nuclear fraction. The t protein had the same molecular mass and shared immunological properties with peroxisomal enoyl-coenzyme-A (CoA) hydratase-3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme. The total cellular amount of n-protein increased 12 h after the administration of 1 microgram T3/100 g BW to thyroidectomized rats. Induction was obvious at 0.1 microgram T3/100 g BW after 24 h. Maximal induction was observed at 0.3 microgram T3/100 g BW. The n-protein was induced when thyroidectomized rat liver was perfused with 10(-7) M T3 for 6 h, excluding the possibility that the effect of T3 was mediated by an extrahepatic factor. The n protein was detected in liver and brain, but not in kidney, heart, testis, or spleen. However, the amount of n-protein in brain was not thyroid hormone dependent. Hepatic n-protein does not correspond to any other T3-responsive protein in terms of its molecular mass and intracellular localization and may be a novel T3-responsive protein. PMID- 1855482 TI - Anionic carbohydrate groups of human thyroglobulin containing both phosphate and sulfate. AB - We showed previously that human thyroglobulin (hTG) contains anionic complex carbohydrate units with up to four sulfate groups, some containing both sulfate and sialic acid. Recent reports indicate that the carbohydrate units of hTG may also contain phosphate, but these reports are not all in accord. The purpose of this study was to confirm the presence of phosphate on the carbohydrate units of hTG and to determine whether phosphate coexists with other acidic moieties, such as sulfate and sialic acid, on the same carbohydrate units. Alkaline phosphatase and acid hydrolysis were used to detect phosphate on the sulfated carbohydrate units of hTG derived from normal and neoplastic tissues. Thyroid fragments from two patients were incubated for 16 h in [35S]sulfate-containing medium, and hTG was purified. Complex carbohydrates were released from hTG with endoglycosidase-F and analyzed at pH 2.2 on a HPLC ion exchange column. Sulfate-containing peaks were monitored by radioactivity, and sialic acid-containing ones were identified by their reduced charge after neuraminidase or acid treatment. None of the sulfate-labeled carbohydrate peaks shifted after alkaline phosphatase treatment alone, indicating that none of them contained phosphomonoesters. Several of the sulfate-labeled peaks shifted after acid hydrolysis, some to positions of decreased charge, due to removal of sialic acid, and some to positions of increased charge, suggesting the presence of phosphodiesters. The latter was confirmed by the observation that some of the newly formed peaks were susceptible to alkaline phosphatase digestion. Thus, acid hydrolysis converted phosphodiesters into alkaline phosphatase-susceptible phosphomonoesters, most likely mannose-6-phosphate. We conclude that some anionic complex carbohydrate units of hTG contain exclusively sulfate, while others contain combinations of sulfate, sialic acid, and phosphodiesters. Phosphodiesters are present in the sulfated carbohydrate units of hTG from normal as well as neoplastic thyroid tissue. PMID- 1855483 TI - Presence and localization of a 30-kDa basic fibroblast growth factor-like protein in rodent testes. AB - We have used a recently characterized rabbit antiserum against basic fibroblast growth factor (bFGF), which recognizes various forms of bFGF, to examine the presence and localization of bFGF in the testes of adult rats and mice and the 5 day-old rat. In Western blots of testicular homogenates of adult rats and mice and immature rats, immunoreactive single bands at approximately 30 kDa were detected. Immunocytochemistry revealed specific staining restricted to the tubular compartment. In 5-day-old rat testes, prespermatogonia were immunoreactive. The cytoplasm of pachytene spermatocytes was heavily stained in the adult testes of both species. Staining of these cells became evident around stage IV/V, was prominent in stage VII through IX and declined about stage XII/XIII (rat) or X-XI (mouse). Staining was seen in type A spermatogonia and in elongating spermatids in their cytoplasmatic lobes and along their flagellae. Sertoli cells were unstained. We propose that the pluripotential growth factor bFGF could be involved in the regulation of germ cell proliferation and differentiation in the adult and immature testis. PMID- 1855484 TI - Isolation and characterization of a human amnion epithelial cell line that expresses the pregnancy-specific beta 1-glycoprotein gene. AB - Human pregnancy-specific beta 1-glycoprotein (PSG) is a family of closely related glycoproteins of 72K, 64K, 62K, and 54K. Together with the carcinoembryonic antigen, they form new members of the immunoglobulin superfamily. To study the molecular mechanisms that regulate expression of the PSG gene, we established a human amnion cell line, HAA58OD-8C, immortalized with an origin-defective simian virus-40 (SV40) temperature-sensitive A58 mutant virus. HAA58OD-8C cells were temperature sensitive for maintenance of transformation and expressed genes encoding PSG and the alpha- and beta-subunits of hCG. At the permissive temperature (33 C; transformed phenotype), they expressed low levels of PSG, hCG alpha, and hCG beta mRNAs and synthesized low levels of a 48K PSG polypeptide. At the nonpermissive temperature (39.5 C), HAA58OD-8C cells exhibited a differentiated phenotype, expressed increased levels of PSG, hCG alpha, and hCG beta mRNAs, and produced high levels of PSG polypeptides of 72K and 48K. Sodium butyrate induced PSG mRNA expression, and in the presence of butyrate, HAA58OD-8C cells produced high amounts of PSG polypeptides of 72K, 62K, and 48K. Ribonuclease protection analysis indicated that similar PSG transcripts were expressed by HAA58OD-8C cells and human term placenta. However, these amnion cells expressed selectively a certain population of PSG transcripts. Our results show that this amnion cell line provides a suitable model for studies of PSG gene expression and regulation. PMID- 1855485 TI - Prolactin-induced mitogenesis of lymphocytes from ovariectomized rats. AB - PRL can induce interleukin-2 (IL-2) receptor expression in splenocytes from ovariectomized (OVX) female rats. In this further study of the effects of PRL on lymphocytes in vitro we found that PRL induced IL-2 receptor expression, IL-2 production, and proliferation of splenocytes and thymocytes from OVX rats. Cells from male rats were not affected. The proliferative response, as measured by [3H]thymidine incorporation, depended on the concentration of PRL and the presence of adherent cells in the culture. After a 48-h incubation with PRL (1 microgram/ml), splenocytes from OVX rats incorporated essentially the same amount of [3H]thymidine as cells incubated with the polyclonal T-cell mitogen Concanavalin-A (ConA). As determined by autoradiography, approximately 40% of the splenocytes responded to PRL or to ConA. After incubation of splenocytes and thymocytes with PRL, bioactive IL-2 was detected in culture medium only from cells of OVX female rats, while incubation with ConA caused IL-2 production by lymphocytes from both male and OVX rats. However, ConA induced IL-2 activity sooner than PRL. Immunofluorescent-flow cytometric analysis revealed time dependent increases in percentages of IL-2 receptor-positive splenocytes as well as increases in percentages of total T-cells and cells of the CD8 and, to a lesser extent, the CD4 subclass after PRL stimulation. PMID- 1855486 TI - Lifestyle and environmental factors as determinants of blood lead levels in a Swiss population. AB - The determination of blood lead levels was included in a Swiss population survey on cardiovascular risk factors in 1984-1985; 931 men and 843 women aged 25 to 75 years participated in the study. Mean blood lead levels (+/- SD) were 0.63 +/- 0.27 mumole/liter for men and 0.44 +/- 0.19 mumole/liter for women, respectively, with a slight increase with age for both sexes. These values are below the maximum level recommended by the Commission of the European Community in 1977; 18 cases were found with blood lead higher than 1.5 mumole/liter and in six of these, a professional exposure was suspected. Smoking habits, drinking habits, and consumption of dairy products were selected as lifestyle descriptors and educational level, occupational category, and size of the community as sociodemographic indicators. Smoking and alcohol consumption show a direct association with blood lead, consuming dairy products an inverse one. Occupation and level of education are significantly related to blood lead only for men, blue collar workers and less-educated men being more exposed. A higher blood lead level in cities was only found for women presumably because they stay at home more often than men and are therefore more sensitive to local exposure. In a multiple stepwise logistic regression, the lifestyle indicators showed a consistently stronger effect on blood lead than sociodemographic indicators. For men, smoking has an effect on blood lead for blue-collar workers much stronger than that for nonindustrial employees and may compound in some way the professional exposure to lead. This stresses the fact that interactions between lifestyle and environmental factors on blood lead are significant, complex, and need further investigation. PMID- 1855487 TI - Effects of 0.60 PPM nitrogen dioxide on circulating and bronchoalveolar lavage lymphocyte phenotypes in healthy subjects. AB - Nitrogen dioxide (NO2) is a common oxidant air pollutant. Animal studies have suggested that NO2 exposure causes a decrease in the numbers of some splenic lymphocyte subtypes and impairs lymphocyte-dependent immune responses. To investigate whether ambient levels of NO2 alter circulating and bronchoalveolar lavage fluid (BALF) human lymphocytes, we studied five healthy nonsmoking adult volunteers. In each subject, blood and bronchoalveolar lavage fluid was obtained and then, more than 2 weeks later, volunteers were exposured to 0.60 ppm NO2 for 2 hr with intermittent light to moderate exercise on 4 separate days within a 6 day period. We measured standard tests of pulmonary function (airway resistance, thoracic gas volume, maximal expiratory flow) and had the subjects rate the severity of respiratory symptoms before and after each NO2 exposure. Circulating and BALF lymphocytes were labeled with fluorochrome-conjugated monoclonal antibodies to human lymphocyte antigens and a flow cytometer was used to count lymphocyte subtypes. Neither any single day's exposure nor all four exposures caused a change in symptoms or in the results of tests of pulmonary function. The total number of circulating lymphocytes obtained after NO2 exposure was slightly greater than at baseline (1792 +/- 544 vs 1598 +/- 549 cells/mm3 at baseline; P = not significant) but the proportions of lymphocyte subtypes did not differ. In the BALF obtained after NO2 exposure and in the baseline state, the total number of lymphocytes and the percentages of T cells (CD 3), B cells (CD 20), T cytotoxic-suppressor cells (CD 8), T helper-inducer cells (CD 4), and large granular lymphocytes (CD 57) also did not differ after NO2 exposure. A slightly but significantly greater proportion of natural killer cells (CD 16) was found in the BALF obtained after NO2 exposure (7.2 +/- 3.1 vs 4.2 +/- 2.4% of total lymphocytes). We conclude that repeated exposures of healthy nonsmoking adults to 0.60 ppm NO2 are not associated with clinically significant symptoms, changes in airway caliber, or alterations in circulating and BALF lymphocyte subtypes. We suggest that brief, daily exposures to NO2 at levels higher than those achieved in urban atmosphere are unlikely to provoke acute respiratory impairment in healthy, nonsmoking adults. PMID- 1855488 TI - Methylene chloride exposure and birthweight in Monroe County, New York. AB - This study examined the relationship between birthweight and exposure to emissions of methylene chloride (DCM) from manufacturing processes of the Eastman Kodak Company at Kodak Park in Rochester, Monroe County, New York. County census tracts were categorized as exposed to high, moderate, low or no DCM based on the Kodak Air Monitoring Program (KAMP) model, a theoretical dispersion model of DCM developed by Eastman Kodak Company. Birthweight and information on variables known to influence birthweight were obtained from 91,302 birth certificates of white singleton births to Monroe County residents from 1976 to 1987. No significant adverse effects of exposure to DCM on birthweight were found. Adjusted birthweight in high exposure census tracts was 18.7 g less than in areas with no exposure (95% confidence interval for the difference between high and no exposure - 51.6, 14.2 g). Problems inherent in the method of estimation of exposure, which may decrease power or bias the results, are discussed. Better methods to estimate exposure to emissions from multiple industrial point sources are needed. PMID- 1855490 TI - Dermal absorption of neat and aqueous volatile organic chemicals in the Fischer 344 rat. AB - Quantification of dermal absorption of volatile organic chemicals (VOCs) from aqueous solutions is required to understand the potential health hazards resulting from skin exposure to these chemicals in contaminated water. Male Fischer 344 rats were dermally exposed (3.1-cm2 dorsal skin) to neat, one-third saturated, two-thirds saturated, or saturated aqueous solutions of 14 VOCs for 24 hr. Blood samples were obtained via indwelling jugular catheters during exposure (0, 0.5, 1, 2, 4, 8, 12, and 24 hr), and analyzed for the VOCs by gas chromatography using headspace analysis. Absorption of the neat VOCs in this series of chemicals decreased as water solubility decreased. Peak blood levels of VOCs attained during exposure for 24 hr to neat chemicals were: 1,2 dichloroethane (135.1 micrograms/ml), bromochloromethane (113.3 micrograms/ml), chloroform (51.0 micrograms/ml), benzene (24.2 micrograms/ml), tetrachloroethylene (21.1 micrograms/ml), dibromomethane (18.2 micrograms/ml), trichloroethylene (11.6 micrograms/ml), toluene (9.5 micrograms/ml), xylene (8.8 micrograms/ml), hexane (8.0 micrograms/ml), ethylbenzene (5.6 micrograms/ml), styrene (5.3 micrograms/ml), carbon tetrachloride (5.0 micrograms/ml), and 1,1,1 trichloroethane (3.4 micrograms/ml). Blood levels of 1,2-dichloroethane and benzene continued to increase during the 24-hr exposure to neat chemical, while blood levels of the other neat VOCs peaked within 4 hr and then either decreased or remained about the same for the duration of the exposure. Absorption of VOCs from one-third, two-thirds, or saturated aqueous solutions was rapid, and resulted in depletion of the chemical from the solution although only a small amount of water was absorbed. Blood levels of each VOC were directly related to the exposure concentrations. The rapid appearance of VOCs in the blood from aqueous solutions demonstrates that detectable amounts of VOCs were absorbed during exposure of only about 1% of the skin surface area of the rat. PMID- 1855489 TI - Chronic carcinogenic and toxic effects of a single subcutaneous dose of cadmium in the male Fischer rat. AB - The carcinogenic effects of cadmium have not been thoroughly assessed in the commonly used Fischer (F344) rat. This study determined tumor incidence in various tissues of male F344/NCr rats after a single dose of cadmium. Cadmium (as CdCl2) was given sc in the dorsal thoracic midline at 30 mumole/kg to 70 8-week old male F344 rats while controls (n = 50) received saline. Rats were observed during the next 90 weeks. Early deaths (less than or equal to 32 weeks), due mostly to acute cadmium-induced hepatotoxicity, accounted for 37 of the cadmium treated rats while no control rats died in the same period. A high incidence of injection site sarcomas (ISS) occurred in the cadmium-treated group (21 ISS/32 rats at risk; 66%) while only 1/50 occurred in controls (2%). In fact, ISS were the major cause of morbidity after 35 weeks in cadmium-treated rats. These tumors were mostly fibrosarcomas, although histiocytic and osteogenic sarcomas also occurred. Testicular interstitial cell tumors, which show a very high spontaneous incidence in this strain (41/49; 84%), were not markedly affected by cadmium (30/31; 97%). This is in sharp contrast to other strains, such as the Wistar, in which cadmium treatment is reported to cause as much as an eightfold increase in interstitial cell (Leydig cell) tumor incidence. The incidence of large granular lymphocyte (LGL) leukemia, which also occurred frequently in control F344 rats (12/47; 26%) was markedly decreased (2/31; 7%) by cadmium. Our recent studies indicate acute lymphonecrotic effects occur with cadmium in lymphoid tissues of rats, and this may be related to the suppression of the leukemia. These results indicate that cadmium is very effective in inducing ISS in F344 rats, as is the case with other strains thus far tested, and also markedly reduces spontaneous leukemia incidence. PMID- 1855492 TI - Effects of ozone on the cholinergic secretory responsiveness of ferret tracheal glands. AB - Oxidant air pollutants exacerbate several pulmonary diseases. Inhalation of ozone has been shown to induce airway smooth muscle hyperresponsiveness. Oxidant injury could also affect airway secretory mechanisms. We postulated that oxidant exposure would alter the glycoconjugate secretory function of airway submucosal glands. To test this hypothesis we examined the effects of in vivo ozone exposure on the in vitro secretory responsiveness of ferret tracheal glands. Ferrets were exposed to 1 ppm ozone, 24 hr/day for 3 or 7 days. Following exposure, glandular explants, denuded of surface epithelial cells, were prepared and incubated in medium containing 3H-glucosamine for 18 hr. Basal secretion of labeled glycoconjugates was significantly increased 31% following 3 days of ozone exposure (P less than or equal to 0.05) and remained elevated 11% after 7 days of exposure compared to the air-exposed group. After 3 or 7 days of exposure to ozone, tracheal gland responsiveness to carbachol was increased as indicated by significantly lower EC50 values (log molar concentration) of -6.43 +/- 0.04 (n = 6) and -6.50 +/- 0.11 (n = 5), respectively; compared to -6.20 +/- 0.08 (n = 6) for the air-exposed group. There was no difference in carbachol EC50 values for air and 7-day ozone-exposed animals treated with dexamethasone. Dexamethasone did not attenuate the ozone-induced increase in basal secretion. Tracheal gland responsiveness to alpha- or beta-adrenergic agonists was not changed by oxidant exposure. These experiments suggest that oxidant injury not only increases basal secretion of respiratory glycoconjugates but also increases tracheal gland sensitivity to a cholinergic agonist. PMID- 1855491 TI - Cytochrome P450IA mRNA expression in feral Hudson River tomcod. AB - We sought to determine if levels of cytochrome P450IA gene expression are environmentally induced in feral populations of Hudson River tomcod, a cancer prone fish, and whether laboratory exposure of tomcod to artificially spiked and naturally contaminated Hudson sediments can elicit a significant response. Using Northern blot analysis, we found levels of P450IA mRNA in tomcod collected from two Hudson River sites higher than those in tomcod from a river in Maine. Depuration of environmentally induced Hudson tomcod P450IA mRNA was rapid, with an initial detectable decline in P450 gene expression by 8 hr and basal levels reached by 5 days. Intraperitoneal injection of beta-napthoflavone in depurated Hudson tomcod resulted in a 15-fold induction of P450 gene expression within 26 hr. Exposure of depurated Hudson tomcod to natural sediment spiked with two PAHs resulted in a 7-fold induction of P450 gene expression. Exposure of depurated tomcod to sediment from a contaminated Hudson site also resulted in a 7- to 15 fold induction of P450IA mRNA expression. Northern blot analysis revealed a second polymorphic cytochrome P450IA mRNA band in some tomcod which was also detected by Southern blot analysis. Induction of cytochrome P450IA mRNA in Atlantic tomcod may provide a sensitive biomarker of environmentally relevant concentrations of some pollutants in the Hudson and other northeastern tidal rivers. PMID- 1855493 TI - Cadmium determination in Mexican-produced tobacco. AB - Exposure to cadmium by inhalation or ingestion is dangerous for human health. This metal induces damage to the kidneys, the bones, the prostate, and the lungs. In the lungs, cadmium can produce cancer, emphysema, and fibrosis. It is well known that tobacco leaves are contaminated with cadmium, a metal that has been related to pulmonary damage. In this paper we report the concentration of cadmium in tobacco leaves and in cigarettes produced for domestic consumption. Fifty-five cigarettes of different brands, prices, and stocks were analyzed as well as 48 samples from four different types of tobacco. The average concentration of cadmium in cigarettes was 4.41 +/- 0.67 micrograms/g, and 2.65 +/- 0.99 micrograms/g for tobacco leaves; the content of cadmium was 2.8 +/- 0.4 micrograms/cigarette. It was estimated that a person that smokes 20 Mexican cigarettes per day can increase his (her) cadmium burden by 1.4 to 2.8 micrograms per day. PMID- 1855494 TI - Regulation of in-place asbestos-containing material. AB - Approximately two-thirds of New York City's 800,000 buildings contain asbestos. Most of this material is damaged or deteriorating. Legislation pending in the New York City Council (Bill number 453) would require virtually all building owners to inspect for asbestos, to develop management and maintenance plans to prevent disturbance of intact material, and to provide notice of the presence of asbestos to building occupants. This paper reviews the legislation and discusses its features that have been questioned. It concludes that regulation of in-place asbestos is necessary and appropriate. PMID- 1855495 TI - Body Mass Index variations: centiles from birth to 87 years. AB - This report provides Body Mass Index (weight/height2) values for the French population from birth to the age of 87 years. BMI curves increase during the first year, decrease until the age of 6, increase again up to 65 years and decrease thereafter. These variations reflect the total changes of fat body mass during life. The 50th centile values of Wt/Ht2 at the ages of 20, 40, 60, 80 years are 21.5, 24.6, 25.4, 24.4 kg/m2 for men and 20.6, 22.6, 24.1, 23.4 kg/m2 for women. The values for the 3rd, 50th and 97th centiles in the middle years are approximately 18, 24 and 32 kg/m2. Graphs for these and four other percentiles are plotted against age, and two other graphs summarising the variation and skewness of the Wt/Ht2 distribution are provided to calculate exact percentiles and Z-scores for individuals. PMID- 1855496 TI - A study of the association between improved sanitation facilities and children's height in Lesotho. AB - The impact of improved sanitation on the anthropometric status of children under 5 years in Lesotho was investigated using children recruited into a case-control study of diarrhoea morbidity. The children's height-for-age Z-scores were used as an indicator of chronic undernutrition. Classifying children as 'stunted' or 'adequately nourished' revealed some evidence of an association between latrine ownership and attained height. After allowing for confounding variables, the odds of stunting were 18 per cent lower among children in households with latrines (95 per cent confidence interval, 36 per cent lower to 3 per cent higher). More powerful analyses, using height-for-age as a continuous outcome variable, revealed that the mean height-for-age Z-score of children from households with a latrine was 0.27 standard deviations higher than that of children from households without a latrine (95 per cent c.i. = 0.12 to 0.42). These results suggest that the anthropometric status of children may be as responsive to improvements in sanitation facilities as diarrhoea morbidity in some settings. PMID- 1855497 TI - Serum lipids and apolipoprotein B values, blood pressure and pulse rate in anorexia nervosa. AB - Some risk factors associated with coronary heart disease (CHD) were evaluated in patients with different types of anorexia nervosa (AN). Anthropometric parameters, serum cholesterol, triglycerides and apoprotein (apo) B values, blood pressure and pulse rate were tested in 29 young female patients and 16 controls. Cholesterol, triglycerides and apo B were higher at the acute period of the illness (AN1), whereas at the chronic period the values of these parameters tended to normalize. Triglycerides were higher in patients who binge ate (bulimarexia). Systolic blood pressure decreased in all types of AN, while diastolic blood pressure decreased only in AN1; pulse rate was not altered. According to cholesterol and apo B values, AN patients may be at risk of CHD if they remain at low body weight. PMID- 1855498 TI - Intake of fluoride and excretion in mothers' milk in a high fluoride (9 ppm) area in Kenya. AB - In 27 nursing mothers a study was made on breast milk fluoride (F) levels and the 24-h intake of F through foods and beverages. The daily F intake averaged 22.1 mg (range 9.5-37.2 mg); cooked food contributed 11.7 mg, water 4.5 mg and tea 5.8 mg. The breast milk F concentration averaged 0.033 mg/l (range 0.011-0.073 mg/l). No significant correlation could be established between the milk F level and the intake of F. The milk F level was, however, correlated positively to mothers' age and negatively to mothers' weight. It is concluded that the milk fluoride level was only moderately increased by the high intake of F, and that the children's intake of F through mothers' milk was negligible compared to the very high F intake through complementary foods and beverages. PMID- 1855499 TI - Inter-observer variability in the measurement of body composition. AB - The inter-observer variation in simple bedside assessments of body composition has been evaluated in 12 healthy adult subjects (6 male and 6 female) by 6 observers. Systematic bias between observers was found to be evident in each of the basic measurements (except height) and in each of the estimates of body composition (except those derived from weight and height alone). The largest residual coefficients of variation (rCV) for the basic measurements were found for skinfold thickness (11-18 per cent for individual skinfold thicknesses, and 9 per cent for the sum of four skinfold thicknesses), and the lowest for weight (0.01 per cent for digital scales, and 0.05 per cent for beam balance) and height (0.4 per cent). The rCV for whole-body resistance (1.2 per cent), forearm resistance (5.4 per cent) and near infra-red interactance (optical density 1: 5.6 per cent and optical density 2: 6.2 per cent) measurements were found to have intermediate values. The variability in the estimate of body fat obtained by skinfold thickness (rCV = 4.6 per cent) and near infra-red interactance methods (rCV = 4.2 per cent) was found to be greater than that from the resistance method (rCV = 2.6 per cent) and by methods based on weight and height alone (rCV = 1.1 per cent). The variability in the estimate of fat-free mass showed the same trend as that for body fat, but the rCVs were less due to the greater mass of the fat free body compared to body fat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855500 TI - Attained height of lacto-ovo vegetarian children and adolescents. AB - The relationship between diet and attained height was studied in children and adolescents in Southern California. Diet pattern was determined from an extensive food frequency questionnaire in 1765 Caucasian children of 7-18 years, attending state schools (452 m and 443 f) and Seventh-day Adventist schools (427 m and 443 f). The major difference in diet pattern between state and Adventist school children was in meat consumption. The Adventist children were split evenly between three categories of frequency in meat consumption (less than 1/week, 1/week-less than 1/d, and greater than or equal to 1/d), while 92 percent of state school children consumed meat daily. Vegetarians (those consuming meat less than 1/week) differed significantly in the consumption of other major food groups, such as fruit and vegetables. All school and diet subgroups were at or above the 50th percentile of the National Center for Health Statistics. Age adjusted regression analysis showed that on average Adventist vegetarian children were taller than their meat-consuming classmates (2.5 and 2.0 cm for boys and girls, respectively). These results did not change materially when adjusting for other food groups. Nor did adjustment for parental height and socioeconomic factors in a sub-sample of 518 children. The results indicate that vegetarian children and adolescents on a balanced diet grow at least as tall as children who consume meat. PMID- 1855501 TI - Mechanisms of gastrointestinal immunoregulation and food induced injury to the gut. PMID- 1855502 TI - Food allergy in children. PMID- 1855503 TI - Adverse reactions to food and drug additives. PMID- 1855504 TI - The clinical use of protein hydrolysates and soya formulae. PMID- 1855505 TI - Food antigens in human milk. PMID- 1855506 TI - Psychoneurological aspects of food allergy. PMID- 1855507 TI - False allergic reactions in children with atopic eczema. PMID- 1855509 TI - The effect of scatter reduction on the signal-to-noise ratio in computed radiography. AB - Signal-to-noise ratio (SNR) in computed radiography (CR) was assessed by using the computerized image data from storage phosphor radiographs in a modification of the Rose model. A multiple pencil-beam (MPB) imaging device, a conventional 1:12 grid, and an air gap of 90 cm were compared in terms of improvement of the signal-to-noise ratio caused by the reduction of scatter. The MPB device showed better SNRs by a factor of 1.25 compared to the grid and air gap which were approximately equal to each other. This is related to its superiority in scatter control, which has also been shown previously. Air gap screening has not been very popular because of geometrical problems, but in scatter reduction it is still comparable to today's grid technology. The optimization of image information content in CR is briefly discussed. PMID- 1855508 TI - Combination of multiple pencil-beam imaging to computed storage phosphor radiography: a new method. AB - Computed radiography (CR) with storage phosphors offers a wide dynamic range and improved sensitivity compared to film-screen technology. CR was combined in this study with a prototype multiple pencil-beam (MPB) imaging device which has been shown to be very effective in scatter reduction. The combination was analyzed and compared to the standard technique of grid screening in two ways: a free-response ROC (FROC) analysis was first performed followed by a blinded test arrangement for visual analysis of image quality in a series of computed radiography of the lumbar spine by both the MPB and grid modalities. The results of the FROC study showed a statistically significant (P less than or equal to 0.01) improvement in signal detection. The MPB-CR images of the lumbar spine had more contrast but also a slightly mottled or grainy appearance. Image quality was found good but contrast processing was criticized because it seemed to result in a too steep display of contrast in MPB imaging. This should be avoidable by changing the image processing parameters. PMID- 1855510 TI - Reject analysis: a pilot programme for image quality management. AB - The radiographic film wastage and the different parameters affecting this wastage were analysed for a 9-week period at a 600-bed University Hospital. An overall reject rate of 7.6% was found. The different reasons for rejection were evaluated, while retake rate, relation between working experience of the personnel, amount of rejected films and total film wastage in surface (m2), were registered and analysed. PMID- 1855511 TI - Assessment of radiology installations in Macedonia, Greece. AB - Nine, small and large radiology installations in Macedonia, Greece using 40 generators and a total of 47 roentgen tubes were assessed and their work load was calculated. The results of quality control measurements in 39 of these (27 radiographic and 12 fluoroscopic tubes) are presented. The parameters measured were: (a) kvp, (b) radiation output, (c) timer accuracy, (d) field coincidence and (e) total filtering. For fluoroscopic equipment spatial resolution and radiation field alignment were also measured. Equipment exploitation seems to be very low, since more than half of the equipment was less than 8 years old, with a work load under 200 mA.min per week. The total work load was calculated to be about 4612 mA.min per week, corresponding to 123,960 patients. These were examined by 52 radiologists supported by 58 radiographers. Skin exposure was measured for fluoroscopy patients (2.8 +/- 2.7 R/mA per min), as well as for a set of routine radiographic examinations. PMID- 1855512 TI - A new apparatus for the localization of nonpalpable mammary lesions. AB - A new apparatus has been used for the localization of 46 nonpalpable mammary lesions seen in either of two radiological projections. This device compresses and immobilizes the breast independently of the mammography equipment and permits a three-dimensional localization of the lesion by using the technique of X-ray angulation. The results demonstrate the efficiency of the procedure. Transfixation of the lesions was established in 30 cases (65.2%), the guidewire passed very close to the lesion in 14 cases (30.4%), and in 2 cases (4.4%) the guidewire was seen to be less than 10 mm away from the lesion. Correct preoperative localization of the lesions permitted a correct diagnosis with minimal biopsies. PMID- 1855513 TI - MRI in primary bone tumors: therapeutic implications. AB - The accuracy of preoperative MRI in detecting tumor extent has been evaluated in 35 patients with primary bone neoplasms; intra-osseous extent was measured on MR images and compared with macroslides of surgical specimens in 26 cases. An almost completely accurate prediction of tumor size was obtained with the combined employment of Spin-Echo (SE) and Short Inversion Time Inversion Recovery (STIR) sequences in the various tumors, with the exception of two Ewing's sarcomas. Changes in Signal Intensity (SI) and tumor morphology were identified in those cases which had undergone presurgical chemotherapy; the reduction in SI and in tumor size or the appearance of a more homogeneous signal was correlated with a positive response to cytotoxic therapy. MR imaging fully satisfies surgeon's preoperative requirements in the assessment of therapy-responding neoplasms as well as in local tumor staging in all types of neoplasms, with the exception of Ewing's sarcoma. PMID- 1855514 TI - Normal brain maturation in MRI. AB - Normal brain maturation was evaluated with MR imaging of 36 neonate to 2-year-old patients. The myelination process in centrum semiovale was quantitatively assessed in 50 6-months- to 15-year-old children, and 40 adults aged 16-60 years. Imaging was performed with a 0.35 T superconducting MR unit using spin echo pulse sequences. On T1-weighted images, three stages of maturation could be observed: (1) neonates within 1 month; (2) 1-6 months of age; and (3) adult configuration after 6-7 months of age. Also on T2-weighted images three maturation stages could be defined: (1) neonatal pattern in the first 6 months of life; (2) signal inversion between 6-18 months; and (3) adult appearance after 18 months. Thus, the combination of T1- and T2-weighted images could lead us to the assessment of brain maturation in infants younger than 2 years. The myelination process in centrum semiovale was fast during the first 3 years followed by slow progression until 20-30 years of age. PMID- 1855515 TI - Extramedullary spinal cysticercosis. PMID- 1855516 TI - Spinal cord cavities: differential-diagnostic criteria in magnetic resonance imaging. AB - MRI examinations of 30 patients with idiopathic syringomyelia and 10 patients with cavities associated with an intramedullary neoplasm were evaluated with respect to typical MRI features in both groups. All tumor-associated cases resembled the idiopathic syringomyelias in some portions of the cavity. At the tumor site, however, tumor-associated cases demonstrated typical findings: the cavities showed abrupt changes of diameter (10/10) and position (8/10) and the surrounding spinal cord demonstrated an uneven thickness (10/10), an increased signal intensity on T2-weighted images (10/10) and pathological contrast enhancement (7/7). Displacement of cerebellar tonsils below the level of the foramen magnum (21/30) and enlargement of the spinal canal (7/29) were characteristic features of idiopathic cases. In conclusion, MRI provides valuable criteria to differentiate between idiopathic and tumor-associated cavities. PMID- 1855517 TI - Intramedullary non-Hodgkin's lymphoma of the spinal cord; a case report. PMID- 1855518 TI - Perfusion characteristics of hepatic cavernous hemangioma using intravenous CT angiography (IVCTA). AB - Thirty-three patients with 35 proven hepatic cavernous hemangiomas (HCH) were studied with intravenous CT angiography (IVCTA). 15 scans were performed during the first 30 s after bolus (6 ml/s) injection of 50 ml iodinated contrast material. Thereafter 2 scans/min were obtained up to 30 min. Three criteria were utilized at IVCTA to make a specific diagnosis of HCH: (1) detection of an intense mural nodular enhancement in the arterial phase. The density in the nodular region(s) should have a density level similar to that of the aorta or hepatic arteries; (2) well-defined nodular area(s); and (3) centripetally oriented enlargement of the nodular region(s). These criteria were seen in 31 of 35 hemangiomas. In contrast the 'typical' Freeny-Marks criteria were present in only 23 of 35 hemangiomas. The results show that our criteria may provide greater specificity. PMID- 1855519 TI - Radiographic findings in pulmonary tuberculosis: the influence of human immunodeficiency virus infection. AB - The chest radiographs and medical records of 166 patients diagnosed as having clinically active pulmonary tuberculosis were reviewed. Forty-nine patients (group I) were seropositives to human immunodeficiency virus (HIV), and 117 patients (group II) did not have known risk factors for HIV infection. Roentgenographic abnormalities were analysed in the two groups, according to nine different radiographic patterns previously defined. The seropositive group had a significantly higher proportion of hilar and/or mediastinal adenopathy (P less than 0.001), infiltrates confined to the lower lung fields (P less than 0.05), and miliary tuberculosis (P less than 0.005). Otherwise, single cavitation and destructive pattern were more frequent in the group II. These data suggest that patients with pulmonary tuberculosis and HIV infection are much more likely to have atypical radiographic findings. PMID- 1855520 TI - Long term clinical care of parkinson's disease. A symposium. Tokyo, April 21, 1990. PMID- 1855521 TI - Transplants in Parkinson's disease. AB - The objectives of this review are, first, to summarize results from clinical trials on patients with Parkinson's disease using grafts of either adrenal medulla or fetal substantia nigra and, second, to discuss some of the scientific issues that need to be clarified in more detail before transplantation can become a real therapeutic alternative in Parkinson's disease. Adrenal medulla autotransplantation using open microsurgery has been shown to effect a modest reduction of the duration and severity of off periods in about 30-50% of operated patients and to have a high morbidity and mortality rate. The mechanisms of improvement are unknown. It is concluded that adrenal medulla autotransplantation is an experimental approach and not a treatment for Parkinson's disease. Animal experimental data clearly favour the use of fetal dopamine (DA) neurons in patients, and clinical trials using such grafts are now going on in several countries. We have implanted human fetal mesencephalic tissue into the striatum in 6 patients. The findings indicate that fetal DA neurons can survive in the human parkinsonian brain and produce therapeutically valuable functional effects. Together with the solid animal experimental data the clinical observations support the idea that neural transplantation can be developed into an effective therapy in Parkinson's disease. However, it should be emphasized that such a treatment is presently not available and that further work is necessary to optimize the transplantation procedure, e.g. with respect to the yield of surviving DA neurons and the location and number of implantation sites to achieve the largest possible symptomatic improvement. PMID- 1855522 TI - Autonomic nervous system disorders in Parkinson's disease. AB - This paper gives a review on the clinical features of autonomic failure which occur in idiopathic Parkinson's disease (PD), mainly based on the recent publications, especially from Japan. In 1817, James Parkinson already mentioned bowel and bladder dysfunctions in his original article. Since then, a number of clinical studies have disclosed the occurrence of autonomic failure in this disease. It is known that relatively minor degrees of orthostatic hypotension are not rare, but other features of autonomic failure are rather uncommon, generally mild in severity and nonprogressive. Orthostatic hypotension is suggested as a possible side effect of L-dopa. Postprandial hypotension is occasionally found, and vasopressin is proven to prevent it remarkably. There is low electrocardiographic R-R interval variability which indicates impaired parasympathetic activity. Thermoregulatory sweating is nearly normal, but its center is functionally impaired. Resting skin temperature is slightly lower. Both salivation and lacrymation are quantitatively within normal limits. Little is known on sexual function in PD. PMID- 1855523 TI - European experience with the urethral Wallstent for urethral strictures. AB - We describe the use of the urethral Wallstent in 71 patients with urethral strictures. The stainless steel stent is self expanding when released from its endoscopic introducer. The results over a 3-year period have been good with only mild discomfort and slight urethral leakage for up to 3 months. Migration, infection and encrustation have not been a problem and serial endoscopic review shows healing to be variable but complete in up to 12 months. It is considered that this simple endoscopic technique offers a simple, safe and effective alternative to multiple dilatations, urethrotomies and urethroplasty procedures in patients with bulbar urethral strictures. PMID- 1855524 TI - Radical retropubic prostatectomy: complications and quality of life (429 cases, 1983-1989). AB - From March 1983 to December 1989 we have performed radical prostatectomy on 429 patients with prostate cancer. With 117 of the cases we performed the sparing nerve procedure. Follow-up was 6-72 months. Early postoperative complications concerned 36 patients (8.4%). We have not had any total incontinence. After a 6 month postoperative period we had a rate of 13.8 +/- 3% of stress incontinence with a confidence level of 95%. This percentage changed to 6.2 +/- 3% after a 12 month period. 33% of the patients after 6 months and 68.5% after 1 year reported full potency with similar pre- and postoperative quality of sexual intercourse. To manage localized prostate cancer it is important to know that with radical prostatectomy we can obtain an excellent quality of life with low morbidity even if the best management of localized prostate cancer is not resolved. PMID- 1855525 TI - Testicular function after unilateral bacterial epididymo-orchitis. AB - In order to determine whether bacterial infection of the gonads may account for some male-related infertility, the fertility status of 45 young men who developed gonococcal urethritis and then epididymo-orchitis were studied prospectively. The fertility potential of the subjects was evaluated through history of paternity, repeated semen examinations, serum follicle-stimulating hormone determinations, and testicular biopsy. Before infection, 14 married men (100%) had proved their fertility through their children. Two years after infection, only 21% of these fathers and 40% of all subjects produced semen considered adequate for conception. The semen values in the rest were comparable to those of infertile/subfertile men. Although the lesion was clinically confined to one testis, testicular biopsy and follicle-stimulating hormone studies showed that testicular damage involved both testes. The study showed that bacterial gonadal infection may result in permanent azoospermia or oligospermia and this without question may result in male-related barrenness. PMID- 1855526 TI - Penile brachial index in impotent patients with coronary artery disease. AB - From March to July 1989, a total of 40 patients, who had received coronary catheterization, answered questionnaires concerning sexual potency. In those 30 patients with a diseased coronary artery, only 2 (6.6%) had no erectile dysfunction subjectively. On the contrary, 4 of 10 (40%) patients with angiographically proven normal coronary artery complained of erectile dysfunction. Penile Doppler ultrasonography was performed in 30 patients. The mean penile brachial index (PBI) of 8 patients with a normal coronary artery was 0.82 +/- 0.1, as compared with the diseased group, 0.73 +/- 0.1 (p = 0.05). When these patients were further divided into two groups by a PBI of greater or less than 0.65, there was also no significant difference in the degree of obstruction of the three main coronary arteries between these two groups. There was no correlation between PBI and obstruction of the left anterior descending artery (r = 0.316, p = 0.689). Most of the patients (93.4%) with an abnormal coronary artery had erectile dysfunction. Nevertheless a poor correlation was noted between the PBI and the severity of coronary artery obstruction. Our study suggests that it is hard to use PBI alone as a predictor of future major thromboembolic heart attack. PMID- 1855527 TI - Diagnostic and therapeutic dilemmas in nontraumatic spontaneous perirenal hemorrhage. AB - We report on 8 patients who presented with acute abdominal pain, palpable mass and a rapid decrease in hemoglobin. Intravenous pyelogram, ultrasound and computed tomography had been performed but the underlying cause of the perirenal hematoma couldn't be detected. Surgical exploration was decided and 6 total and 2 partial nephrectomies were performed. The pathological report revealed 4 adenocarcinomas and 4 angiomyolipomas. The possibility of spontaneous rupture of the kidney in the evaluation of cases of acute abdomen is particularly stressed. PMID- 1855528 TI - Onlay urethroplasty with parameatal foreskin flap for distal hypospadias. AB - A new technique of onlay flap urethroplasty is described. The cosmetic and functional results of this logical extension of our one-stage urethroplasty with parameatal foreskin-flap have been good. The onlay urethroplasty with parameatal foreskin flap was recommended for the repair of distal hypospadias without chordee. PMID- 1855529 TI - Long-term follow-up after extracorporeal shock wave lithotripsy in children. AB - In 34 children (25 girls and 9 boys), aged 1-14 years, extracorporeal shock wave lithotripsy (ESWL) was performed for renal and ureteral calculi between March 1985 and December 31, 1989. The patients were treated with the HM3-Dornier lithotripter under general anesthesia. Of the 34 children, 24 with an interval of more than 12 months since ESWL were called in for control check up, 17 of them ultimately came. Seven were lost for long-term follow-up as they moved out of the area. The children were free of urinary symptoms and without urinary tract infections. Creatinine was normal and urinalyses were negative in all 17 children. 16/17 children were stone free and had normal blood pressure, 1 patient with a polycystic kidney on the left nontreated side already demonstrated elevated pretreatment blood pressure. Radioisotope examinations with separate clearance tests gave results in the normal range in 14/17 patients. The sonographic findings on the longitudinal and transverse diameter of the treated and untreated kidneys did not show marked differences as they all remain below the 5% limit. PMID- 1855530 TI - Combined effect of tumor necrosis factor alpha and anticancer chemotherapeutic agents against human renal carcinoma cell lines. AB - Antitumor effect of recombinant human tumor necrosis factor alpha (TNF) alone or in combination with various anticancer chemotherapeutic agents was tested using an in vitro antiproliferative assay on four human renal carcinoma cell lines (VMRC-RCW, VMRC-RCZ, Caki-1 and A-498). When the dose-dependent effect of TNF was studied, none of the four cell lines showed a 50% or more inhibition even at a concentration of 10,000 U/ml of TNF, so that the susceptibility to TNF was low. An enhancing effect of TNF on the cytotoxic effect of almost all the chemotherapeutic agents tested was observed against VMRC-RCZ and A-498. Against VMRC-RCW and Caki-1, the combination of TNF with the chemotherapeutic agents did not result in an enhancing effect. Mitomycin C showed an enhancing effect of TNF against all four cell lines. These results suggested that the combined treatment of TNF with chemotherapeutic agents may have favorable results in clinical trials. PMID- 1855531 TI - Role of inhibitor deficiency in urolithiasis. II. Deficiency grade-adjusted and intermittent augmentation therapy for magnesium and citrate deficiency. AB - 63 patients with hypocitraturia (44.9% of the total) and 33 patients with hypomagnesiuria (24.8% of the total) received oral magnesium hydroxide and/or Na/K citrate in addition to other therapeutic agents if indicated and a common sense diet. Hypocitraturic patients were categorized into 3 groups and received 27-81 mEq/day oral citrate according to the deficiency grade. Hypomagnesiuric patients also formed two groups according to the deficiency grade and received 500 and 1,000 mg/day magnesium hydroxide, respectively. Replacement was intermittant and was controlled every 3 months until reaching normal values. We evaluated 28 of 63 hypocitraturic and 15 of 33 hypomagnesiuric patients who had inhibitory deficiency as the sole causal factor of their urolithiasis. After a follow-up of 13.5 +/- 10.2 months, no patient in either group developed a new stone. Citrate and magnesium were increased significantly in the respective groups; calcium and oxalate excretion was lowered, and urine pH and volume increased significantly. A deficiency grade-adjusted and intermittant replacement therapy with Mg and citrate is very effective, has less side effects and ensures good patients compliance. PMID- 1855532 TI - Immunofluorescent study on the interaction between collagen and calcium oxalate crystals in the renal tubules. AB - The interaction of calcium oxalate crystals and renal tubular cells was studied. Rat renal collecting tubular cells were cultured and immunologically stained with anti-type-IV collagen antiserum (type-IV collagen exists in renal tubular basement membrane). When renal tubular cells and calcium oxalate crystals were mixed, clumps were formed. These clumps were examined by immunological staining with anti-type-IV collagen antiserum. In another series of experiments, calcium containing crystals were found to be adsorbed onto mucous threads and cast-like materials, although no such adsorption was observed on squamous cells. These absorbed materials interacted with anti-type-IV collagen antiserum. These results suggest that collagen in the renal tubular basement membrane may act as matrix in urinary stone formation. PMID- 1855533 TI - Uridine, xanthine and urate concentrations in prostatic fluid and seminal plasma of patients with prostatitis. AB - The etiology of prostatitis is not fully understood and several causative factors have been considered in the past. In this study we analyzed the expressed prostatic secretion (EPS) and seminal plasma with regard to uridine, xanthine, urate, creatinine and zinc from patients with prostatitis (the diagnosis was based on symptoms for at least 1 year), together with creatinine, urate and zinc in the serum. In 8 of the patients, a direct comparison of these constituents was performed between EPS and seminal plasma. EPS contained low concentrations of uridine and xanthine and high concentrations of creatinine and zinc as opposed to seminal plasma that displayed a reverse pattern. The mean urate concentration in seminal plasma, exceeding that of EPS by 78%, was rather close to the mean value found in serum but no significant correlation was seen between urate in serum and urate in seminal plasma or EPS. Urate in EPS correlated significantly to xanthine in EPS and such a relationship was also observed between urate and creatinine in EPS. In seminal plasma, urate and xanthine were likewise correlated with each other. On division of the patients into a high-score symptom group and a low score group, no intergroup differences were found in EPS and seminal plasma constituents. Hence, we found high concentrations especially of uridine and xanthine in seminal plasma, compared with other body fluids, and evidence of a backflow of urine mixing with the prostatic fluid of these patients was seen. We suggest that crystal formation of these metabolites may occur under certain conditions and could constitute a first step in the development of prostatitis vesiculitis-epididymitis in some cases. PMID- 1855534 TI - Growing teratoma syndrome successfully treated with lymphoblastoid interferon. AB - In most instances mature teratoma can be successfully resected following chemotherapy for advanced testicular cancer. However, some patients may eventually die because of uncontrollable local growth of an unresectable growing mature teratoma. This is a report on a patient with an unresectable growing mature teratoma in whom a long-lasting disease stabilization was achieved after treatment with lymphoblastoid interferon. PMID- 1855536 TI - Prosthetic replacement of the inferior vena cava in renal cell carcinoma surgery. AB - An aggressive surgical approach is needed in cases of renal cell carcinoma with extension into the vena cava, since caval extension is not such a bad prognostic indicator as previously believed. Improvements in peri- and intra-operative management have enabled the resection of the tumor thrombus at all levels of the caval extension with acceptable morbidity and mortality. In cases where there is direct major invasion of the venal caval wall, we recommended complete resection of the involved segment and re-establishment of caval continuity using a polytetrafluorethylene (PTFE) interposition graft. Two cases, in whom segmental caval resection was necessary, are reported. The pre- and intra-operative considerations are discussed together with support for the use of PTFE as the graft of choice. PMID- 1855535 TI - Self introduction of urethrovesical foreign bodies. PMID- 1855537 TI - Incomplete quadruplication of urinary tract with contralateral agenesis of the kidney. AB - We describe here the first case of an exceptional anomaly consisting of an incomplete quadruplication of the urinary tract in a solitary left kidney. A review of the English literature failed to document such a case. PMID- 1855538 TI - Dextran sulfate inhibits the inositol 1,4,5-trisphosphate-induced Ca2+ release from skinned and cultured smooth muscle cells. AB - Dextran sulfate inhibited the inositol 1,4,5-trisphosphate (IP3)-induced decrease in 45Ca2+ content, in a dose-dependent manner, in saponin-skinned and primary cultured smooth muscle cells from the rat aorta. The maximum inhibition was observed at 3-10 mg/ml, and the IC50 was about 173 micrograms/ml. Dextran sulfate also inhibited the IP3-induced increase in 45Ca2+ efflux rate, but did not affect the caffeine-induced Ca2+ release. Dextran sulfate inhibited the specific binding of [4,5-32P]IP3 to the skinned cells, thereby indicating that it may have an effect on the IP3 receptor. Dextran (without the sulfates) had no inhibitory effect on either the IP3-induced Ca2+ release or on the specific binding of [4,5 32P]IP3. Thus, sulfate groups on the molecule of dextran sulfate may play an important role in the inhibition of the IP3-induced Ca2+ release from intracellular stores. PMID- 1855539 TI - Angiotensin II receptors in the rat lung are of the AII-1 subtype. AB - In the rat lung [3H]angiotensin II ([3H]AII) recognizes a single class of binding sites with an equilibrium constant (KD) of 2.8 +/- 0.9 nM. The corresponding receptor density (Bmax) was 704 +/- 60 fmol/mg protein. Equilibrium of [3H]AII binding was reached after 60 min. The dissociation of the radioligand was strongly influenced by mono- and divalent cations and the non-hydrolyzable GTP analog 5'-guanylyl-imido-diphosphate (Gpp[NH]p), indicating the interaction with a G protein. Specific binding of [3H]AII to rat lung preparations was inhibited by different agonists and antagonists and sensitive to DuP 753 (2-n-butyl-4 chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)bi phe nyl-4-yl) methyl]imidazol, potassium salt) but insensitive to PD 123177 (1-(4-amino-3-methyl-benzyl)-5 diphenylacetyl-4,5,6,7-tetrahydro-i midazo [4,5-c]pyridine-6-carboxylic acid) two non-peptide AII antagonists selective for either the AII-1 or AII-2 subtype. Furthermore, specific [3H]AII binding was inhibited by dithiothreitol. It is concluded that in the rat lung [3H]AII binds to receptors of the AII-1 subtype which are coupled to a G protein. These receptors may be involved in the regulation of pulmonary perfusion and resistance. PMID- 1855540 TI - The effects of age on phosphatic metabolites of the human crystalline lens. AB - Paired human lenses ranging from 2 to 96 yr old (n = 17) were harvested within 2 hr post-mortem and immersed in liquid nitrogen. Phosphorus containing metabolites from perchloric acid extracts were quantitated using phosphorus-31 nuclear magnetic resonance spectroscopy. Low-energy metabolites detected include the phosphomonoesters (PME) hexose-6 phosphate, alpha-glycerol phosphate, fructose 1,6-diphosphate, beta-glycerol phosphate (beta-GP), uncharacterized phosphomonoesters at 4.63 delta, 4.34 delta and 3.05 delta, phosphorylethanolamine (PE), inosine and adenosine monophosphates, and phosphorylcholine (PC). Inorganic orthophosphate (Pi), glucose 1-phosphate and glycerol 3-phosphorylcholine were the other low-energy metabolites detected. High energy metabolites phosphocreatine (PCr), adenosine tri- and di-phosphates (ATP, ADP), nucleoside diphosphorylsugars (NS) and the dinucleotides were also detected. The following metabolic indices were calculated: PCr/Pi, PME/Pi; ATP/Pi, PCr/ATP, ATP/ADP, PE + PC, PC/PE, energy charge, phosphorylation potential, and the energy modulus. A significant linear increase with age (P less than 0.05) occurred only in the uncharacterized resonance at 3.05 delta (r = 0.4593). Significant linear decreases with age (P less than 0.05) occurred in the uncharacterized resonance at 4.63 delta (r = -0.5950), beta-GP (r = -0.5018), PCr (r = -0.4495), N.S. (r = -0.4882). There was a significant (P less than 0.05) linear decrease in the energy modulus (ratio of high-energy to low-energy metabolites). PMID- 1855541 TI - Nuclear breakdown during terminal differentiation of primary lens fibres in mice: a transmission electron microscopic study. AB - The pre and post-natal development of wild type mouse lenses was studied by transmission electron microscopy, with special emphasis on denucleation of primary lens fibres. Denucleation of primary fibres is characterized by nuclear accumulation of small granules, most likely nucleosomes, which are condensed to osmiophilic bodies in the nucleus and in the cytoplasm. The osmiophilic bodies are laid down in apposition to the fibre membrane and are invaded by vesicles and granules, which probably contain proteolytic enzymes. Part of the breakdown products are extruded into the extracellular space, transported to the anterior and posterior poles where they might be finally digested or discarded from the lens. The morphology of the denucleation process of primary fibres is different from the gradual fading of nuclei in secondary fibres as described by Kuwabara and Imaizumi (1974: Invest. Ophthalmol. Vis. Sci. 13, 973-81). PMID- 1855542 TI - Optimal conditions for long-term photoreceptor cell rescue in RCS rats: the necessity for healthy RPE transplants. AB - Retinal pigment epithelial (RPE) cells from normal Long-Evans, healthy Royal College of Surgeons (RCS) pigmented congenic (rdy+p+) and RCS pigmented dystrophic rats were transplanted into retinas of RCS non-pigmented dystrophic rats at post-natal days 17 and 26 (P17 and P26). When examined at P60, rescued photoreceptor cells were found in all transplanted groups. In addition, a small, but significant increase in the outer nuclear layer (ONL) thickness was detected in retinas injected with vehicle (sham control); however, the ONL thickness was reduced to control levels by 3-5 months after injections in both the sham controls and the group grafted with RCS pigmented dystrophic RPE cells. Likewise, large volumes of vehicle were injected into the subretinal space resulting in no long lasting beneficial effects. Also, there was no significant difference between the ONL thickness in retinas grafted with RCS congenic RPE and those grafted with Long-Evans RPE. When donor RPE cells from Long-Evans rats at neonatal and adult stages were transplanted into P26 RCS hosts, photoreceptor cell rescue could be found; however, the younger RPE cells affected a better rescue than those derived from adult eyes. In addition, when RPE cells from 6- to 9-day-old Long-Evans rats were transplanted into retinas of RCS dystrophic rats at 10, 17 and 26 days, significant rescue of photoreceptor cells was observed. Of these transplantation times, day 17 appeared to affect the best rescue of photoreceptor cells up to 1 yr. In contrast, little or no rescue was observed in the retinas of those RCS dystrophic rats when RPE cell transplantation was performed at P38, P43 and P48. The photoreceptor cell rescue was also found to be dependent on the concentration of RPE cells injected, which was maximal at 60,000 120,000 cells microliters-1. These findings lead us to conclude that in order to affect long-term, up to 1 yr, rescue of photoreceptor cells in the RCS rat, young, healthy RPE cells are required and transplantation needs to be performed at early stages of the disease process. PMID- 1855543 TI - Different cell populations in bovine trabecular meshwork: an ultrastructural and immunocytochemical study. AB - Bovine outflow tissue differs markedly from that of humans. Tissue culture studies on the cells of this region are often compared with those of primate trabecular meshwork cells. A thorough cytological and immunocytochemical characterization of the cells of the bovine chamber angle is lacking. We have therefore investigated the cells of the pectinate ligament, the reticular meshwork, the region adjacent to the aqueous plexus, the connective tissue region between reticular meshwork and ciliary muscle and the ciliary muscle itself, ultrastructurally and immunocytochemically with staining for the cytoskeletal proteins vimentin and desmin, for alpha-smooth muscle-actin and rough endoplasmic reticulum (rER). In the pectinate ligament and in the region adjacent to the aqueous plexus, the cells were found to have especially abundant rER and glycogen in their cytoplasm. Vimentin was abundant in the reticular meshwork as positive staining was seen both in frozen and paraffin sections. Alpha-smooth muscle-actin could be found in the region connecting ciliary muscle and reticular meshwork as well as in a small area adjacent to the posterior capillary loops of the aqueous plexus. Ultrastructurally, these cells resembled myofibroblasts. The ciliary muscle cells stained both for vimentin and for alpha-smooth muscle actin. PMID- 1855544 TI - The cone matrix sheath in the normal and diseased retina: cytochemical and biochemical studies of peanut agglutinin-binding proteins in cone and rod-cone degeneration. AB - The fate of the cone-associated extracellular domain, or cone matrix sheath (CMS), was examined in two canine models of hereditary retinal degeneration. The diseases, which affect cones selectively (cd = cone degeneration), or rods and cones temporally (prcd = progressive rod-cone degeneration), were examined biochemically (SDS-PAGE/lectin blots) and cytochemically (light microscopy) using peanut agglutinin lectin (PNA) to selectively label this domain and associated structures. Most of the cones had disappeared in the adult cd retina. In the remaining cones, PNA labeled the ectopically located somata and the CMSs that were present around severely diseased ones. Loss of cones resulted in background label in the IPM and the loss of the pedicle-associated label in the OPL. SDS PAGE of retinal extracts showed that all the major classes of the lower molecular weight PNA-binding proteins were present, but only the 40- and 60-kD bands remained prominent. Because of the selectivity of the cd mutation, this suggests considerable heterogeneity within the various size classifications of the retinal PNA-binding glycoproteins. In prcd, CMSs were normal at a time when cones were structurally normal and disease was limited to the rod outer segments. The CMSs remained intact during the degenerative phase of the disease, and only became compressed in association with the collapse and narrowing of the photoreceptor layer; CMS labeling was lost with disappearance of the cone inner segment. The lectin biochemical results were normal until 1.7 years of age; thereafter, there was a decreased prominence of all major bands. Because of spatial heterogeneity in disease severity, it was not possible to correlate the lectin biochemical and cytochemical results in prcd. PMID- 1855545 TI - Effect of pigmentation on glutathione redox cycle antioxidant defense in whole as well as different regions of human cataractous lens. AB - 'Reactive oxygen species', generated within the lens, are implicated in the deepening of nuclear pigmentation leading to browning of the human cataractous lens. The present study, which was carried out in senile brunescent cataracts, deals with changes in the antioxidant glutathione redox cycle defense system during the progression of browning (yellow to brown) in different regions of the human lens. A significant reduction in the levels of reduced glutathione was noted in the cortical and nuclear regions of the brown lens as compared to yellow lens, despite normal glutathione reductase activity. The rate limiting enzyme of the hexosemonophosphate shunt pathway, glucose 6-phosphate dehydrogenase, and the important oxidant scavenger enzyme, glutathione peroxidase, showed significant changes in opposite directions (glucose 6-phosphate dehydrogenase increased and glutathione peroxidase decreased), only in the cortical region of the brown lens as compared to yellow lens. The significance of the present findings in relation to the overall biochemical mechanisms underlying browning of the lens tissue in human cataracts is discussed. PMID- 1855546 TI - Outflow facility studies in the perfused human ocular anterior segment. AB - We have recently developed a tissue model of the human aqueous outflow pathway involving placement of the eviscerated anterior corneoscleral shell, [with lens and uveal tissue removed but trabecular meshwork (TM) attached] onto a specialized perfusion apparatus. The TM and associated outflow tissues are perfused with culture medium at a physiologically-relevant perfusion pressure in a 5% CO2 environment at 37 degrees C. Under these conditions, the perfused outflow tissues are similar for several days, to the human and/or subhuman primate outflow system in vivo with regard to morphology as well as several functional parameters. Measured facility of outflow (0.271 +/- 0.018 microliters min-1 mmHg-1, n = 79) is similar to facility values obtained by tonography in living human beings. Moreover, outflow facility decreases in a linear fashion with increased perfusion pressure by 1.4% mmHg-1. Finally the removal of the TM results in a 41% decrease in measured outflow resistance. The ability to study viable human outflow tissue for at least several days and the opportunity to establish a model which serves as an alternative to animal testing, point to the potential importance of this technique in investigating the biology of the aqueous outflow system. PMID- 1855547 TI - Extracellular proteases in developing chick neural retina. AB - During retinal histogenesis, cells and their extensions migrate within the tissue to final positions. In order for the cells to move through the matrix of tissue, space must be made available. We report evidence that extracellular proteolytic activity might be associated with this process. (1) When embryonic chick neural retinal cells are seeded onto a substrate of rhodamine conjugated fluorescent gelatin, the tips of growing neurites remove the fluorescence from the substrate. (2) Latent gelatinolytic activity can be identified with soluble assays of homogenates of embryonic chick neural retina. (3) Zymogram analysis demonstrates the presence of high molecular weight bands of proteolytic activity. The activity is inhibited by 1.10 phenanthroline, suggesting that it is due to a metalloproteinase. Activity can be detected in supernatants of retinal cells grown in vitro. Gelatinolysis is not the only proteolytic activity detected in the retina. Addition of plasminogen to zymograms results in an additional band of activity. PMID- 1855548 TI - Microtubules rich in post-translationally modified alpha-tubulin form distinct arrays in frog lens epithelial cells. AB - Isolated frog lens epithelia were stained with antibodies against tyrosinated, detyrosinated or acetylated alpha-tubulin and observed by several means including a scanning confocal microscope. The most prominent feature of Rana pipiens lens cells was a primary cilium close to the apical surface of the cells above the centrosome. This structure was associated with microtubules rich in modified alpha-tubulin. The cilium was less pronounced but still discernible in the cells of another species R. ridibunda. In both species, the modified (acetylated or detyrosinated) microtubules formed arrays spatially distinct from the unmodified (tyrosinated) microtubules. The modified microtubules formed a basket of microtubules with a curly distribution around the nucleus while the tyrosinated array consisted predominantly of rather straighter microtubules running from the apical centrosome to the cell periphery, down the lateral sides of the cells and across the basal surface adjacent to the lens capsule and basement membrane. It is concluded that the organization of modified microtubules previously described for several types of cultured cells may represent a remnant of the three dimensional perinuclear array of such microtubules described here for the cells of an intact epithelium. PMID- 1855549 TI - Muscarinic antagonist effects on experimental chick myopia. PMID- 1855550 TI - Retinoic acid decreases the number of EGF receptors in corneal epithelium and Chang conjunctival cells. PMID- 1855551 TI - Quantitative study of striate single unit responses in monkeys performing an orientation discrimination task. AB - Contour orientation discrimination accuracy is determined by the orientation bandwidth, response variance and response strength of single units that code for orientation. We measured the latter three properties for V1 cells of monkeys which were performing an orientation discrimination of the grating stimulating the cell under study. We recorded from 285 cells, of which 76% responded to the grating. The orientation bandwidth, measured as full width at half height of the tuning curve, varied over a wide range amongst cells. The median bandwidth was 41 degrees. The response variance of the cells also varied considerably between cells; on average it was about two times the response strength. We also studied the temporal properties of the responses. Most of our cells had a latency between 40 and 100 ms. The response variance was found to be smaller in the initial phases of the response than at the later response stages. In some cells the orientation tuning varied in successive stages of the response, while in others the orientation bandwidth and preferred orientation remained stable throughout the response. However, all orientation sensitive cells were orientation tuned from the start of the response, a property which contribute to the fast and reliable coding of contour orientation. These results provide for the first time an estimation of the orientation tuning properties of V1 cells during visual orientation discrimination. They will be very useful to compare single cell properties of other areas to as well as in simulation studies of models of primate visual discriminations. PMID- 1855553 TI - Integration in trigeminal premotor interneurones in the cat. 2. Functional characteristics of neurones in the subnucleus-gamma of the oral nucleus of the spinal trigeminal tract with a projection to the digastric motoneurone subnucleus. AB - Seventy-one (n = 71) premotor interneurones have been localized by extracellular recordings within the subnucleus-gamma of the oral nucleus of the spinal trigeminal tract (NVspo-gamma) in nineteen chloralose anaesthetized cats. The neurons were antidromically activated by microstimulation (minimum = 3 microA) applied to the digastric motoneurone subnucleus of the trigeminal motor nucleus. Fifty-one (n = 51) of the interneurones were discharged from the ipsi- and nineteen (n = 19) from the contralateral digastric subnucleus. One neurone out of four tested was antidromically activated from both stimulation sites suggesting a bifurcated axon. The identified premotor neurones had a unique convergence profile of oral and perioral primary afferents. Latency calculations indicated that at least 55% of these interneurones were monosynaptically activated by low stimulus strength applied to the inferior alveolar (minimum = 1.0 T) and/or the lingual nerve (minimum = 1.0 T). The thresholds for evoking the neuronal discharges coincided statistically with those required to evoke a jaw opening reflex response by stimulation of the same nerves. It is suggested that the specific group of NVspo-gamma interneurones under different contexts mediates the disynaptic reflex and participates in the centrally and reflexly evoked "patterning" adjustments of the digastric jaw opening motoneurones during ongoing jaw movements. A companion paper reports the convergence of descending cortical, tectal and ascending cervical inputs, as well as of oro-facial and neck primary afferent inputs onto an unselected population of interneurones in the NVspo-gamma (Westberg and Olsson 1991). PMID- 1855552 TI - Integration in trigeminal premotor interneurones in the cat. 1. Functional characteristics of neurones in the subnucleus-gamma of the oral nucleus of the spinal trigeminal tract. AB - The profile of integration in a sample of 183 interneurones localized in the subnucleus-gamma of the oral nucleus of the spinal trigeminal tract (NVspo-gamma) has been analyzed. 134 neurones were tested for inputs from primary afferents of the trigeminal, facial and cervical nerves as well as for inputs from the midbrain and from the cervical spinal cord. The remaining 49 neurones were tested for inputs from the primary afferents and for descending convergence from defined sites within the oro-facial primary projections of the cerebral cortex. It was found that the interneurones, mainly recorded in the dorsal and dorsomedial aspect of the NVspo-gamma, receive short latency inputs from the low threshold oral and perioral afferents and longer latency inputs from the high threshold jaw and neck muscle afferents. There was evidence for convergence from the cervical segmental level (29%) and some of the neurones had axon terminals in the superior colliculus. However, the interneurones did not receive a descending tectal input. About 80% of the NVspo-gamma interneurones were activated from the orofacial primary projection fields within cytoarchitectonic areas 3a and 3b of the coronal gyrus. This input was topographically organized and the neurones were activated from the same oral and perioral region of the periphery as the cortical region from which the descending projections themselves originated. Minimum latencies indicated a monosynaptic connection. The convergence profile onto the NVspo-gamma interneurones appeared unique as compared with interneurones located in the intertrigeminal area. Aspects of the possible functional roles of the NVspo-gamma neurones are discussed in relation to ongoing oro-facial ("masticatory") movements. The properties of a selected sample of NVspo-gamma interneurones, which were antidromically activated from the digastric subnucleus of the trigeminal motor nucleus, are reported in a companion paper (Olsson and Westberg 1991). PMID- 1855555 TI - Peripherally evoked single unit responses in ventroposterolateral nucleus in the absence of the dorsal column nuclei in rat. AB - The present experiments were designed to determine the effects of removing the dorsal column nuclei on the evoked responses of the ventroposterolateral nucleus (VPL) neurons in the rat. Previously, we have observed inhibitory interactions between forelimb and hindlimb inputs to VPL (Roberts and Wells 1990), and have also observed a synaptic recovery process within VPL following dorsal column nuclei (DCN) lesions (Wells and Tripp 1987). In an attempt to describe any changes in VPL responses that correlate with the synaptic recovery in VPL following lesions to the DCN, we have studied the incidence of the inhibition process in VPL, the latency of activation of single unit VPL responses to peripheral nerve stimulation, the number of evoked unit responses observed per track studied and the somatotopy of responses in VPL. Dorsal column nuclei lesions did not alter the incidence or duration of the inhibitory interaction between forelimb and hindlimb inputs to VPL. Following DCN lesions, there was a significant increase in the latency to activation of VPL neurons by both forelimb and hindlimb inputs. This increase in latency returned to a non-significant difference from control over the same interval of time that is required for the structural recovery in VPL. There was a significant reduction in the number of evoked unit responses observed per track studied in the deafferented group at the twenty day post-lesion time course. This difference was no longer statistically significant in the sixty-four day post-lesion group. Finally, we have observed little change in the overall anatomic distribution of responses to forelimb or hindlimb stimulation in VPL following DCN lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855554 TI - Neurons of the pretectal area convey spinal input to the motor thalamus of the cat. AB - The aim of this study was to corroborate lesioning work (Mackel and Noda 1989), suggesting the pretectal area of the rostral midbrain acts as a relay between the spinal cord and the ventrolateral (VL) nucleus of the thalamus. For this purpose, extracellular recordings were made from neurons in the pretectal area which were antidromically activated by stimulation in the rostral thalamus, particularly in VL. The neurons were tested for input from the dorsal columns of the spinal cord, the dorsal column nuclei, and the ventral quadrant of the spinal cord. Latencies of the antidromic responses ranged between 0.6 and 3.0 ms (median 1.0 ms): no differences in latencies were associated with either location of the neurons in the pretectal area or with the site of their thalamic projection. Orthodromic responses to stimulation of ascending pathways were seen in the majority of neurons throughout the pretectal area sampled. Latencies of orthodromic responses varied considerably, with ranges of 0.9-9 ms, 6-20 ms, and 2.5-20 ms upon stimulating the dorsal column nuclei, dorsal columns, and ventrolateral quadrant, respectively. The shortest-latency responses to stimulation of the dorsal column nuclei or of the ventral quadrant were likely to be monosynaptic. Temporal and spatial facilitation of the responses to ascending input were common. The data show that neurons of the pretectal area are capable of relaying somatosensory input ascending from the spinal cord to the rostral thalamus. It is suggested that the pretectofugal output to VL converges with cerebellar input in VL neurons and becomes incorporated in cerebello-cerebral interactions and, ultimately, the control of movement. PMID- 1855556 TI - Response of adult cat abducens internuclear interneurons to selective removal of their target motoneurons. AB - The morphological and physiological integrity of abducens internuclear interneurons was evaluated following chemical removal of their almost exclusive target, i.e. the contralateral medial rectus motoneuron population. Motoneuron death was induced by toxic ricin injection into the ipsilateral medial rectus muscle. The main advantage of this method is that target removal is not associated with presynaptic axon damage. The activity of identified abducens internuclear interneurons was recorded before and after target removal during spontaneous eye movements in the chronic cat preparation. Several abnormalities and a remarkable decrease in eye position and velocity sensitivities were observed in the discharge pattern of these neurons for a period of 15-20 days following target removal. After that time all recorded interneurons behaved normally. A parallel morphological study showed the absence of any abducens internuclear interneuron death. These results indicate that, after a critical period, the abducens internuclear interneuron population recovers its normal behavior following target removal with no evidence of neuronal loss. PMID- 1855557 TI - Intracerebroventricular vasopressin reduces CSF absorption rate in the conscious goat. AB - Cerebrospinal fluid (CSF) levels of vasopressin (AVP) are elevated in some disorders associated with raised intracranial pressure. We have previously demonstrated that intracerebroventricular infusion of AVP in the conscious goat leads to elevation of intracranial pressure by a mechanism independent of changes in arterial blood pressure or circulating neurohypophysial peptide concentrations. We have now examined the effect of increasing CSF AVP levels on CSF dynamics using the technique of ventriculo-cisternal perfusion in the conscious goat. Intracerebroventricular perfusion with 5 pmol/min AVP in artificial CSF did not alter CSF formation rate but significantly reduced CSF absorption rate (24% decrease; p less than 0.01), when compared with perfusion using artificial CSF alone. This AVP-mediated reduction in CSF absorption rate may represent increased resistance to resorption of CSF or may reflect the effect of raised intracranial pressure. PMID- 1855558 TI - Interneurones of the lumbar cord related to spontaneous locomotor activity in the rabbit. I. Rhythmically active interneurones. AB - In decorticate, unanaesthetized and curarized rabbit preparations displaying spontaneous fictive locomotor sequences, the firing pattern of neurones was recorded extracellularly in the L6-S1 spinal cord. These neurones, located in the intermediate part of the cord, were not invaded by antidromic stimulation of the hindlimb muscle nerves and thus were considered as interneurones (or propriospinal or tract cells ascending to the brain). When compared to the output from the ipsilateral muscle nerves, these neurones were classified as flexor (F INs) or extensor (E INs) according to the phase of the locomotor cycle when they displayed their maximal firing rate. Among 69 F INs, 33 maintained tonic firing during the periods between episodes of locomotor activity. Their maximal firing rate was in phase with the flexor efferent bursts of the locomotor sequence; during the extensor phase, they maintained an instantaneous frequency (i.f.) that was clearly above the resting i.f. Of these neurones, six became completely silent during the initial flexorextensor coactivation that opened the sequence (F1 neurones) whereas the 27 others increased their firing rate at that time (F2 neurones). The other neurones (36 F3) were silent between the locomotor episodes. Although most of them had a rhythmic activity limited to the flexor bursts, some fired throughout locomotor sequence with a maximal rate during flexor bursts. All the 123 E neurones completely stopped firing during the flexor phase. As was the case for F3 neurone firing, E3 neurone firing (34 neurones) occurred only during periods of locomotor activity. Among the neurones that displayed tonic activity between locomotor episodes, the E2 neurones (24 from 123) remained at this resting value during the extensor phase whereas the E1 neurones (65 neurones) showed an increased i.f. for all or part of this phase. These data, which suggest an asymmetrical genesis of the flexor and extensor activities in locomotion, need to be supported by further analysis. PMID- 1855559 TI - The effect of muscle length on motor unit discharge characteristics in human tibialis anterior muscle. AB - Muscle length influences the contractile properties of muscle in that when muscle is lengthened the relaxation phase of the muscle twitch is prolonged and when muscle is shortened, the relaxation phase is shorter in duration. As a result, the force exerted by active motor units varies with muscle length during voluntary contractions. To determine if motoneuron spike trains were adjusted to accommodate for changes in the contractile properties imposed by shortened and lengthened muscle, motor unit action potentials were recorded from the tibialis anterior muscle at different muscle lengths. Twenty subjects performed isometric ramp contractions at ankle angles of 20 degrees dorsiflexion, neutral between dorsiflexion and plantar flexion, and 30 degrees plantar flexion, which put the tibialis anterior muscle in a shortened, neutral, or lengthened condition, respectively. During isometric contractions where torque increased at 5% MVC/s, motor unit discharge rate at recruitment was greater in shortened muscle than in lengthened muscle (P less than 0.05). Brief initial interspike intervals (less than 40 ms) occurred more frequently in shortened muscle than in either neutral length or lengthened muscle. During steady contractions, motor unit discharge rate was greater per unit torque (N.m) in shortened muscle than in neutral length or lengthened muscle (P less than 0.05). These findings indicate that muscle length does influence the discharge pattern of motor unit spike trains during isometric ramp contractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855560 TI - Direction and amplitude precuing has no effect on automatic posture responses. AB - Automatic postural responses of leg muscles to the sudden displacement of standing support were investigated under four different conditions of information given to subjects in advance. Results from three groups of subjects were compared: 6 normal subjects, 10 patients with cerebellar disease, and 9 patients with Parkinson's disease. Specifically, each subject was provided with visual information about the direction and/or the amplitude of an upcoming platform tilt. For the control situation no advance information on the characteristics of platform tilt was provided. Neither the latencies nor the integrals of postural EMG-responses showed alterations with advance information. In contrast, in a control experiment in which 3 normal subjects had to perform large or small forward or backward voluntary movements of the body around the ankle joint, shorter onset-latencies of leg muscle EMG responses were observed with increasing complexity of the advance information. These results suggest that, unlike voluntary movements, postural responses to rapid surface tilts do not benefit from advance visual information on direction or amplitude of a postural disturbance. PMID- 1855561 TI - Serotonin and cervical respiratory motoneurones: intracellular study in the newborn rat brainstem-spinal cord preparation. AB - Previous experiments performed in the in vitro newborn rat brainstem-spinal cord preparation reported that the addition of serotonin (5-HT, 30-50 microM) to the bathing medium induced increases in the respiratory frequency and a large tonic discharge on all the cervical ventral roots. The aim of the present work was to define whether the 5-HT-induced tonic discharge involved respiratory or non respiratory motoneurones. Intracellular recordings demonstrated that cervical (C2) motoneurones (n = 27) were depolarized by 5-HT but that the 5-HT-induced tonic discharge was mainly due to recruitment of silent motoneurones (n = 18) which fired permanently (15/18; 17 +/- 3 Hz) under 5-HT. The respiratory motoneurones (n = 9) retained a phasic inspiratory discharge (5/9), even if some (4/9) occasionally exhibited a few spikes during expiration. Therefore, it is concluded that the 5-HT-induced tonic discharge is unlikely to have functional significance in respiration. PMID- 1855562 TI - Visually-induced adaptive plasticity in the human vestibulo-ocular reflex. AB - The vestibulo-ocular reflex (VOR) is under adaptive control which corrects VOR performance when visual-vestibular mismatch arises during head movements. However, the dynamic characteristics of VOR adaptive plasticity remain controversial. In this study, eye movements (coil technique) were recorded from normal human subjects during sinusoidal rotations in darkness before and after 8 h. of adaptation to 2X binocular lenses. The VOR was studied at 7 frequencies between 0.025 and 4.0 Hz at 50 degrees/s peak head velocity (less for 2.5-4 Hz). For 0.025 and 0.25 Hz, the VOR was tested at 4 peak head velocities between 50 and 300 degrees/s. Before 2X lens adaptation, VOR gain was around 0.9 at 2.5-4.0 Hz and dropped gradually with decreasing frequency to under 0.6 at 0.025 Hz. Phase showed a small lead at the highest frequencies which declined to 0 degree as frequency decreased to 0.5-0.25 Hz, but then rose to 14 degrees by 0.025 Hz. VOR gain was independent of head velocity in the range 50-300 degrees/s at both 0.025 and 0.25 Hz. However, Phase lead rose with increasing head velocity, more so at 0.025 than at 0.25 Hz. After 2X lens adaptation, gain rose across the frequency bandwidth. However, the proportional gain enhancement was frequency dependent; it was greatest at 0.025 Hz (44%), and declined with increasing frequency to reach a minimum at 4 Hz (19%). Phase lead increased after 2X lens adaptation at lower frequencies, but decreased at higher frequencies. New velocity-dependent gain nonlinearities also developed which were not present prior to adaptation; gain declined as peak head velocity increased from 50 to 300 degrees/s at both 0.025 (23% drop) and 0.25 Hz (15% drop). This may suggest an amplitude-dependent limitation in VOR adaptive plasticity. Results indicate both frequency and amplitude dependent nonlinearities in human VOR response dynamics before and after adaptive gain recalibration. PMID- 1855563 TI - Adaptive plasticity in the gaze stabilizing synergy of slow and saccadic eye movements. AB - When a normal human subject is briefly turned in total darkness while trying to "look" at a spatially fixed target, the vestibulo-ocular reflex (VOR) produces slow-phase compensatory eye movements tending to hold the eyes on target. However, slow-phase compensation per se is generally inadequate in these circumstances. Nevertheless it has recently been found, that even in the dark, this inadequacy tends to be corrected by supplementary saccades usually acting in the compensatory direction. The present study further investigates this phenomenon by measuring the respective contributions of saccadic, slow-phase and overall net compensation in 9 subjects tested before and after 30% adaptive attenuation of VOR slow-phase gain. In each test series, subjects attempted to stabilize their gaze on a previously seen target during each of 40 brief (approximately 0.5 s) whole body rotations (40 degrees/s, 20 degrees amp) conducted in complete darkness. The adaptive experience comprised 2 h of full field visual suppression of the VOR during sinusoidal rotation of subject and surround at 1/6 Hz and 40 degrees/s velocity amplitude. Before adaptation, the cumulative slow-phase and cumulative saccadic components produced on average 78% and 14% respectively of the ideal (100%) compensation, thus yielding an overall net compensation which was 92% of the desired value. After adaptation, the corresponding values in the same population were 53%, 18% and 71% respectively. Thus after adaptation, the combined saccadic-slow-phase response brought the final gaze position to a point in space that was systematically shifted in the direction of head rotation (i.e. undercompensation). Subjects re-exposed to 30 min of normal visual-vestibular interaction displayed a variety of recovery patterns using different combinations of slow and saccadic eye movements. However, there was a consistent "synergistic" tendency for saccadic eye movements to improve slow-phase performance, regardless of the subject's adaptive state. In one subject, compensatory saccadic eye movements corrected a consistent directional asymmetry in the slow-phase response. It is suggested that a conscious vestibular percept of self-rotation might underlie the combined saccadic-slow-phase response, and that the net under performance after adaptation might reflect attenuation of this percept relative to the actual rotational stimulus. PMID- 1855564 TI - Adaptive modification of vestibularly perceived rotation. AB - Results from Bloomberg et al. (1991) led to the hypothesis that saccades which accompany the dark-tested vestibulo-ocular reflex (VOR) tend to move the eyes towards a vestibularly derived percept of an intended oculomotor goal: also that this is so even when that percept has been adaptively modified by suitably prolonged visual-vestibular conflict. The present experiments investigate these implications by comparing the combined VOR + saccade performance with a presumed "motor readout" of the normal and adaptively modified vestibular percept. The methods employed were similar to those of an earlier study Bloomberg et al. (1988) in which it was found that after cessation of a brief passive whole body rotation in the dark, a previously seen earth-fixed target can be accurately located by saccadic eye movements based on a vestibular memory of the preceding head rotation; the so-called "Vestibular Memory-Contingent Saccade" (VMCS) paradigm. The results showed that the vestibular perceptual response, as measured after rotation by means of the VMCS paradigm, was on average indistinguishable from the combined VOR + saccade response measured during rotation. Furthermore, this was so in both the normal and adapted states. We conclude that these findings substantiate the above hypothesis. The results incidentally reaffirm the adaptive modifiability of vestibular perception, emphasing the need for active maintenance of its proper calibration according to behavioural context. PMID- 1855565 TI - Relationships between sensory responsiveness and premovement activity of quickly adapting neurons in areas 3b and 1 of monkey primary somatosensory cortex. AB - When monkeys make wrist movements in response to vibration of their hands, primary somatosensory (SI) cortical neurons that adapt quickly to the vibratory stimulus often exhibit two temporally separate types of activity. Initially, these neurons respond to the stimulus. They then cease discharging, only to resume firing prior to the movement. This activation, cessation and reactivation occurs even though the sensory stimulus remains on until after the movement is begun. The first change in activity is most likely related to sensory input. The second, which has been called premovement activity, may have a sensory component as well as one related to the upcoming movement. We wanted to test the hypothesis that the premovement activity exhibited when vibration is present represents both a reactivation of a neuron's vibratory response and the premovement activity that normally occurs when vibration is absent. We also wanted to determine if area 3b and 1 quickly adapting (QA) neurons show similar or different activity patterns during the initiation and execution of sensory triggered wrist movements. Four monkeys were trained to make wrist flexion and extension movements in response to vibratory stimuli delivered to the handle which the animals used to control the behavioral paradigm. Two fo the four monkeys also made similar wrist movements following visual cues. We found that the premovement activity of QA neurons located in area 1 (but not area 3b) is comprised of a sensory-related component as well as a movement-related component. The magnitude of these individual components differs in relationship to a neuron's receptive field type, the movement direction and the external force imposed on the stimulated forelimb. Premovement activity of area 3b and area 1 QA neurons occurs at the same time prior to movement, regardless of whether visual or vibratory cues are used to trigger wrist movements. This activity occurs at about the same time as others have observed elevations in the threshold for tactile perception, suggesting that premovement activity and changes in sensory responsiveness before movement may be related. These and previous findings are used to construct a model which may predict the firing patterns of SI QA neurons during behavioral tasks. These findings also suggest that areas 3b and 1 may have different roles in processing task-related somatosensory information. PMID- 1855567 TI - Mechanical load on the ventilatory muscles during an incremental cycle ergometer test. AB - An incremental cycle ergometer test performed with a total of 40 healthy subjects (25 male, 15 female) was used to study the mechanical load on the ventilatory muscles. The parameters for the mechanical load on the ventilatory muscles are the time integral of the oesophageal pressure and the mean oesophageal pressure change per time unit (dPoe/dTI) of each breathing manoeuvre. The pressure-time integral is the area delimited by the oesophageal pressure trace and the inspiratory time axis. It is expressed as a fraction of the product of the subject's maximum oesophageal pressure (Poe(max)) and total breath cycle duration (TTOT). This parameter is called oesophageal tension time index (TTIoe). The relationship between minute ventilation and these two parameters during ergometer test showed gender-specific variations because of the differences between men and women as to anthropometric data, lung function parameters and maximum ventilatory muscle strength. Moreover, the dPoe/dTI values significantly depend on the breathing frequency. The present study has provided evidence that, in general, the TTIoe and dPoe/dTI values in terms of a specific minute ventilation (VE) are higher in women than in men. Parameters for the mechanical load on the ventilatory muscles regarding the level of pressure to be generated as well as the duration and velocity of muscle contraction should therefore also allow for the gender of the patients. PMID- 1855566 TI - Influence of moderate hypothermia on ischemic brain damage incurred under hyperglycemic conditions. AB - Preischemic hyperglycemia aggravates brain damage following transient ischemia, and adds some special features to the damage incurred, notably a high frequency of postischemic seizures, cellular edema, and affectation of additional brain structures, such as the substanta nigra pars reticulata (SNPR). We raised the question whether mild intra-ischemic hypothermia (32-33 degrees C), known to reduce selective neuronal vulnerability in normoglycemic subjects, also ameliorates the characteristic damage observed in hyperglycemic animals. To that end, two series of experiments were performed. In the first, normo- and hypothermic animals were subjected to 10 min of ischemia during hyperglycemic conditions (plasma glucose 20-25 mmol.l-1), and allowed either 15 h or 1 week of recovery. In the second, both normo- and hyperglycemic animals were subjected to 15 min of ischemia (at normal or reduced temperature) and surviving animals were studied after 1 week of recovery. All normothermic, hyperglycemic animals developed postischemic seizures and died within the first 24 h. Mild hypothermia afforded substantial protection. Thus, 6/7 hypothermic animals subjected to 10 min of ischemia survived 1 week of recovery and none developed post-ischemic seizures. Of the hypothermic animals subjected to 15 min of ischemia 6/11 survived for 1 week, only one of which developed seizures. Protection by hypothermia was also shown by the histopathological analysis. Experiments with 10 min of ischemia and 15 h of recovery showed the expected damage in normothermic, hyperglycemic subjects. Hypothermia markedly reduced damage in all vulnerable structures, including the cingulate cortex and SNPR. The protection was most pronounced in the caudoputamen, where no affected neurons were seen in the hypothermic subjects. The experiments with 15 min of ischemia confirmed previous findings that mild hypothermia protects normoglycemic animals against the insult. The results also showed that hypothermia prevented most of the exaggeration of damage caused by hyperglycemia. However, under hypothermic conditions hyperglycemia still augmented damage in the cingulate cortex, medial and lateral venteroposterior thalamic nuclei, and SNPR, structures specifically damaged under hyperglycemic, normothermic conditions. This suggests that hypothermia has less of a protective effect on mechanisms causing such damage than on neuronal damage in the classic selectively vulnerable regions, particularly the caudoputamen. PMID- 1855568 TI - Diagnostic tests of hyperventilation syndrome. AB - In 90 patients referred to the pulmonary function laboratory for evaluation of hyperventilation syndrome (HVS) and in whom somatic causes of the complaints had been excluded, we investigated the degree of concordance between three widely applied diagnostic methods: 1) the standardized Nijmegen questionnaire on major daily complaints; 2) the reproduction of the same symptoms during the hyperventilation provocation test (HVPT); and 3) the responses of end-tidal CO2 fraction (FETCO2) during the HVPT. In 86% of the patients a concordance was found between Nijmegen questionnaire (i.e. score of 24/64 or more) and symptom reproduction during HVPT (i.e. recognition of at least 2 major daily complaints). Based on these combined data we made a definite diagnosis of HVS in 37 patients, of non-HVS in 40 patients, and we retained only a possible HVS in 13 patients. Each of the 16 complaints in the questionnaire contributed significantly to the distinction between HVS and non-HVS patients, and a striking similarity in rank order of daily complaints and reproduced symptoms was found. The responses in FETCO, during HVPT had little additional diagnostic value. A spontaneous fall of at least 0.25% FETCO2 during the 5 min adaptation period before the HVPT, was most reliably correlated with the aforementioned diagnostic criteria of HVS: specificity 83%, sensitivity 57%, and accuracy 70%. Neither the 3 min FETCO2 ratio nor the 5 min FETCO2 ratio during recovery after the HVPT showed a good correlation with the other diagnostic criteria. The response of FETCO2 during HVPT did especially not provide additional useful diagnostic information in the 13 patients with only possible HVS. PMID- 1855570 TI - Comparison of maximal airway narrowing to methacholine between children and adults. AB - Bronchial hyperresponsiveness in adults is characterized by an increased sensitivity as well as an elevated maximal response to inhaled bronchoconstrictors. In children, however, it is unknown whether the maximal response increases with increasing sensitivity. We investigated the maximal degree of airway narrowing to methacholine in nonasthmatic and asthmatic children (7-12 yrs), and compared it to that in adults. Nineteen children (9 normals, 10 asthmatics) and 19 adults (8 normals, 11 asthmatics) were selected in order to cover a wide distribution of bronchial responsiveness. All subjects underwent 2 methacholine challenge tests on separate days, by inhaling doubling doses using a standardized dosimeter technique (up to a noncumulative dose of 59 mumol). The response was measured by forced expiratory volume in one second (FEV1) and expressed as a percentage fall from baseline value. The complete dose-response curves were characterized by their position (PD20, the provocative dose causing a 20% fall in FEV1) and maximal response (MFEV1, the mean response on the plateau, defined as greater than or equal to 2 points within a 5% response range). Plateaus were observed in 13 children and 9 adults, the coefficient of repeatability of MFEV1 being 10.8 and 10.4% fall, respectively. There was an inverse relationship between log PD20 and MFEV1, which did not differ between children and adults (p greater than 0.15). In most of the asthmatic children and adults the plateau could not be measured (exceeding 50% fall in FEV1) if PD20 was less than 1 mumol. We conclude that, for a given bronchial sensitivity, the maximal response to inhaled methacholine is similar between children and adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855569 TI - Alveolar macrophages in idiopathic pulmonary fibrosis display a more monocyte like immunophenotype and an increased release of free oxygen radicals. AB - Bronchoalveolar lavage (BAL) was performed in 13 patients with idiopathic pulmonary fibrosis (IPF) and in 10 control subjects. Free oxygen radical (FOR) production of alveolar macrophages (AM) and of blood monocytes was measured by luminol-dependent chemiluminescence (LDCL) without and after stimulation with zymosan A. We confirmed earlier studies that alveolar macrophages of IPF patients display a significantly elevated release of FOR under basic and under stimulated conditions. In contrast to alveolar macrophages, blood monocytes did not reveal altered LDCL in IPF. This indicates that the functional properties for augmented FOR release by IPF alveolar macrophages are acquired in the lungs and not in the peripheral circulation. To elucidate the possible mechanisms leading to the augmented LDCL response, immunophenotyping of alveolar macrophages was carried out. A panel of new monoclonal antibodies of the Ki-M-series, discriminating differentiation stages of monocyte/macrophage subpopulations, served for immunocytochemical staining. In IPF patients distribution of Ki-M2, Ki-M3, Ki-M6 and Ki-M8 positive AM demonstrated an increased proportion of alveolar macrophages expressing a more monocyte-like immunophenotype. Normally, monocytes as precursors of AM reveal a markedly stronger LDCL than alveolar macrophages themselves. Therefore, it seems likely that the increased LDCL of alveolar macrophages in IPF is due to the higher proportion of more immature monocyte-like cells in the alveoli of these patients. PMID- 1855571 TI - Mortality and morbidity from respiratory diseases in childhood in The Netherlands, 1980-1987. AB - National mortality and hospitalization data from the Netherlands were analysed for asthma (International Classification of Diseases) (ICD 493), acute bronchi(oli)tis (ICD 466), pneumonia and influenza (ICD 480-487), and other chronic obstructive pulmonary diseases (ICD 490 + 491 + 492 + 496) in children aged 0-14 yrs for 1980-1987. No trends were seen in the mortality in age groups 0 4 yrs and 5-14 yrs, which actually concerned small numbers. In general a tendency towards increasing hospital admission rates for respiratory diseases was observed in both sexes in age groups 0-4 yrs and 5-9 yrs but not in age group 10-14 yrs, and significant increases were found for asthma in males and females aged 0-4 yrs and in males aged 5-9 yrs, and for acute bronchitis in females aged 5-9 yrs. Hospital admission rates in the Netherlands for asthma appeared to be low compared to other countries. The average length of stay, however, for both asthma and the other respiratory diseases was substantial though declining. Clinical information is required on possible causal factors of the apparent need for hospitalization for reactive airway disorders in young children, and on the management of asthma in particular. PMID- 1855572 TI - Domiciliary investigation of sleep-related hypoxaemia in Duchenne muscular dystrophy. AB - In Duchenne muscular dystrophy (DMD) nocturnal oxygen desaturation occurs during rapid eye movement (REM) sleep. Polysomnography, which requires hospital admission, will detect sleep-related breathing abnormalities. In order to avoid the inconvenience of hospital admission for the disabled patient, we investigated overnight oxygenation in ten boys with DMD by domiciliary oximetry. In four boys the results of oximetry were compared with those of a polysomnographic recording. The "repeatability" of domiciliary oximetry was assessed in six boys by performing oximetry on two non-consecutive nights. Older boys with DMD may develop a cardiomyopathy. In order to assess cardiac rhythm and ST segment changes we performed simultaneous Holter monitoring and oximetry in seven boys with overnight hypoxaemia. Six of the initial ten boys studied demonstrated episodic nocturnal hypoxaemia and there was a strong correlation between minimum oxygen saturation overnight and daytime arterial oxygen and carbon dioxide tensions (PaO2 r = 0.89; PaCO2 r = -0.87). Despite adequate REM time during polysomnography, greater oxygen desaturation was found during domiciliary oximetry. No difference was found in the severity of desaturation recorded in the boys who were studied on two separate occasions. Five boys demonstrated marked heart rate variation during hypoxaemic episodes and more serious arrhythmias occurred overnight in the three most hypoxaemic boys. Domiciliary oximetry is a simple, repeatable method of assessing overnight oxygenation and compares well with polysomnography. In boys with advanced DMD and severe nocturnal hypoxaemia, 24 h electrocardiographic monitoring may detect potentially life-threatening arrhythmias. PMID- 1855573 TI - Intestinal calcium absorption and parathyroid hormone secretion in asthmatic patients on prolonged oral or inhaled steroid treatment. AB - A secondary hyperparathyroidism resulting from decreased intestinal calcium (Ca) absorption has been proposed as a contributory factor to glucocorticoid-induced osteoporosis. Inhaled steroids do not usually suppress adrenal gland function unless daily doses above 1,500 microgram are used. A recent study, however, has shown a reduced total body calcium in patients on regular beclomethasone treatment. In theory, osteopenia in these patients could be due to a direct effect of inhaled steroids on bone or due to an impaired intestinal calcium absorption. In this study, Ca absorption and parathyroid hormone (PTH) secretion were evaluated in three groups: 1) asthmatics on continuous oral and inhaled steroid treatment (11.3 +/- 4.4, range 5-33.5 mg.day-1 prednisone and 660 +/- 265, range 400-1,600 microgram.day-1 beclomethasone, respectively); 2) asthmatics on regular beclomethasone therapy (585 +/- 210, range 400-1,200 microgram.day-1); and 3) healthy subjects. The prevalence of vertebral fractures was evaluated by a spinal X-ray. No differences were found in either Ca absorption or PTH serum levels between asthmatics and healthy subjects (analysis of variance-ANOVA). Vertebral fractures were significantly more frequent in patients from group 1 (14 of 25) than in those from group 2 (2 or 25). We conclude that both prolonged oral steroid treatment and inhaled steroids, at doses lower than 1,600 microgram.day-1 do not cause Ca malabsorption, and that hyperparathyroidism does not contribute to osteoporosis in these patients. PMID- 1855574 TI - Hyperreactivity and 45Ca movements in sensitized guinea-pig tracheal muscle. AB - Responses to KCl and histamine and 45Ca movements were studied in trachea from normal and actively sensitized guinea-pigs. Sensitized tracheas were hyperresponsive and hypersensitive to KCl and histamine. 45Ca uptake experiments show that sensitized tracheal muscle behaves as normal except that the uptake of 45Ca in low concentration (0.03 mM) Ca2+ solution was higher and the number of binding sites for the high affinity component of 45Ca uptake (as estimated by Scatchard-coordinate plot) was augmented. Additionally, in sensitized tracheal muscle, incubation in low (0.03 mM) Ca2+ solution followed by La3+ wash-out resulted in a greater amount of residual 45Ca than in normal tissues. KCl, but not histamine, increased the La3+ resistant 45Ca content. This increase was greater in sensitized than in normal trachea. This demonstrates the existence of hyperreactivity and altered 45Ca movements in sensitized trachealis muscle. PMID- 1855575 TI - A single-compartment model cannot describe passive expiration in intubated, paralysed humans. AB - The time-course of thoracic volume changes (respiratory inductive plethysmograph) during relaxed expiration was studied in 11 intubated, paralysed, mechanically ventilated subjects. The semilog volume-time curves show that expiration is governed by two apparently separate mechanisms: one causes emptying of most of the expired volume (approximately 80%) with a time constant of 0.50 +/- 0.22 s for a baseline tidal volume of 0.44 +/- 0.12 l (mean +/- SD) and 0.37 +/- 0.14 s when the tidal volume is reduced (VTP); the other contributes a relatively small amount to the expired volume over a significantly longer time, the time constant amounting to 3.27 +/- 1.54 s for baseline VT and 2.95 +/- 1.65 s for VTp. The first mechanism probably reflects the standard elastic and flow resistive properties of the respiratory system, while the second, slower compartment, is probably an expression of the viscoelastic properties of the pulmonary and chest wall tissues. PMID- 1855576 TI - Drug-induced lung disease: 1990 review. AB - Numerous drug-induced pulmonary manifestations have been reported but studies of their pathogenic mechanisms are still rare. These mechanisms should, however, be precisely determined in order to identify subjects at risk and to prevent some of these complications by the proper use of certain drugs in more appropriate conditions. The possibility of an iatrogenic manifestation should always be considered in patients developing pulmonary symptoms. Data from biological investigations, although not specific, contribute to the understanding of lung injury mechanisms. PMID- 1855577 TI - The Dutch hypothesis (chronic non-specific lung disease) revisited. AB - In 1961 the hypothesis (later referred to as the Dutch Hypothesis (DH)) was put forward that asthma, chronic bronchitis and emphysema should be considered as different expressions of one disease entity, in which both endogenous (host) and exogenous (environmental) factors play a role in the pathogenesis. A hereditary predisposition to develop allergy and bronchial hyperreactivity were considered to be important denominators of disease susceptibility. Complications and complicating diseases would also contribute to the ultimate phenotype of the patient. In the present paper we discuss the relevance of this hypothesis in 1990. Until now it has not been refuted; circumstantial evidence in its favour has accumulated, but formal proof is still lacking. Further research should pay more attention to the genetic aspects of the disease. Arguments are presented against the use of the terms asthma, chronic bronchitis, and emphysema as indicators of disease entities, and in favour of the use of an umbrella-term, e.g. chronic non-specific lung disease (CNSLD), provided that, in addition, every patient is characterized using so-called defining criteria. PMID- 1855578 TI - A "splitting" look at chronic nonspecific lung disease (CNSLD): common features but diverse pathogenesis. AB - The term chronic nonspecific lung disease (CNSLD) was proposed by the Ciba Symposium in 1959 as an umbrella term grouping chronic bronchitis, asthma, emphysema and irreversible or persistent obstructive lung disease. However, it has only been widely used by proponents of the Dutch Hypothesis, which states that these diseases all result from a common genetic root and should be considered as one disease. A major reason for proposing this hypothesis in 1961 was that these different entities share some common features, especially airway hyperresponsiveness. Although not formally disproven, evidence is accumulating- and reviewed here--against this "one disease concept"; hence, common features should not necessarily imply a common pathogenesis. Overlap features are sufficiently frequent in clinical practice to cause problems for labelling patients within the scope of CNSLD. The term could still be used as a starting point for a "splitting approach", identifying a small number of important basic features in order to allow a more systematic use of established labels for diseases within CNSLD. Our proposal for labelling emphasizes a consistent use of asthma, emphysema and chronic obstructive pulmonary disease (COPD), but restricts the use of chronic bronchitis to those patients with chronic bronchial hypersecretion without chronic airways obstruction. PMID- 1855579 TI - A comparison of the Yan and a dosimeter method for methacholine challenge in experienced and inexperienced subjects. AB - Bronchial reactivity is being measured with increasing frequency in epidemiological studies, but there debate continues about the relative merits of the different methods used to measure reactivity, particularly for subjects with no previous experience of reactivity testing as is the case in epidemiological studies. Repeatability is likely to improve with practice, and laboratory based studies on experienced subjects may overestimate the repeatability of a test in inexperienced subjects. We have compared the repeatability of the Yan method with a dosimeter (Mefar) method of administering methacholine to 40 asthmatic subjects: 20 with experience of methacholine challenge on at least six previous occasions and 20 with no previous experience. Subjects attended the laboratory on four days within a two week period, at the same time of day. A methacholine challenge was performed on two occasions using the Yan method and on two occasions using the dosimeter. Methacholine responsiveness was measured as the provocative dose causing a 20% reduction in forced expiratory volume in one second (PD20FEV1). Geometric mean PD20FEV1 values with the Yan method were 1.14 doubling doses (DD) of methacholine higher than with the dosimeter method. In the experienced subjects, the 95% range for a single estimate was +/- 1.56 DD for the Yan method and +/- 1.37 DD for the dosimeter method. In the inexperienced subjects, the 95% ranges were +/- 2.65 and +/- 1.87 DD for the Yan and dosimeter methods, respectively. Thus, the differences in repeatability between the Yan and dosimeter methods, were small; experienced subjects gave more repeatable values than inexperienced subjects. PMID- 1855580 TI - Adult respiratory distress syndrome (ARDS) due to bacteraemic pneumococcal pneumonia. AB - We describe a patient, who had no pre-existing disease, with bacteraemic pneumococcal pneumonia and adult respiratory distress syndrome (ARDS), a rare complication. In spite of the use of antibiotics and intensive treatment the mortality rate of this kind of infection remains high. Streptococcus pneumoniae is the most frequently found micro-organism responsible for community-acquired pneumonia. In 25-35% of these patients pneumococcal bacteraemia is found, with a 2-3 times higher mortality rate than that for non-bacteraemic pneumococcal pneumonia. PMID- 1855581 TI - Pain in scar as an early symptom of acquired thoracic lung hernia. AB - Hernia of the lung manifests itself as an elastic, usually replaceable, swelling in the chest wall, which changes in size during inspiration and expiration. It does not generally cause any symptoms. We describe the case history of a 49 yr old man with an acquired thoracic lung hernia, which had first presented three years previously as pain in an operation scar during coughing and lifting. Histopathology of the excised lung tissue showed abnormalities suggestive of previous episodes of strangulation. PMID- 1855582 TI - Neurilemmoma of the intrathoracic vagus nerve. AB - A neurilemmoma (Schwannoma) of the left intrathoracic vagus nerve was discovered on a chest radiograph of a 28 yr old woman and was removed via a left thoracotomy. Although neurogenic tumours are the most common tumours of the mediastinum, they rarely involve the intrathoracic vagus nerve. PMID- 1855583 TI - DNA methylation and chromatin structure. AB - Studies of the whole genome by molecular and cytogenetic methods have implicated DNA methylation in the formation of 'inactive chromatin'. This has been confirmed by analysis of specific endogenous sequences, and has been mimicked by introducing methylated and non-methylated sequences into cells. As well as affecting chromatin structure. DNA methylation also represses transcription. A protein (MeCP) which binds specifically to methylated DNA has been identified. The properties of MeCP could account for the effects of DNA methylation on both chromatin and transcription. PMID- 1855584 TI - On the origins of genetic variants. AB - Two contrasting mechanisms responsible for the creation of genetic variants are described: one is the manifestation of the limited accuracy of the cellular machinery for DNA replication, the other results from the ability of cells to repair damaged DNA. Replication-dependent variants and those caused by episodical DNA damage enhance the probability that a small fraction of a cell population may survive a sudden (physical or biological) change of environmental conditions. Replication-independent variants arise during persistent but not immediately lethal stress (e.g. starvation) of a non-dividing population. The variants observed under these conditions are of selective advantage because they are able to cope with the particular stress situation. The molecular basis of their creation is a matter of intensive debate. PMID- 1855585 TI - Codon bias and gene expression. AB - The frequencies with which individual synonymous codons are used to code their cognate amino acids is quite variable from genome to genome and within genomes, from gene to gene. One particularly well documented codon bias is that associated with highly expressed genes in bacteria as well as in yeast; this is the so called major codon bias. Here, it is suggested that the major codon bias is not an arrangement for regulating individual gene expression. Instead, the data suggest that this codon bias, which is correlated with a corresponding bias of tRNA abundance, is a global arrangement for optimizing the growth efficiency of cells. On the practical side, it is suggested that heterologous gene expression is not as sensitive to codon bias as previously thought, but that it is quite sensitive to other characteristics of the heterologous gene. PMID- 1855586 TI - Regulation of protein synthesis at the elongation stage. New insights into the control of gene expression in eukaryotes. AB - There are many reports which demonstrate that the rate of protein biosynthesis at the elongation stage is actively regulated in eukaryotic cells. Possible physiological roles for this type of regulation are: the coordination of translation of mRNA with different initiation rate constants; regulation of transition between different physiological states of a cell, such as transition between stages of the cell cycle; and in general, any situation where the maintenance of a particular physiological state is dependent on continuous protein synthesis. A number of covalent modifications of elongation factors offer potential mechanisms for such regulation. Among the various modifications of elongation factors, phosphorylation of eEF-2 by the specific Ca2+calmodulin dependent eEF-2 kinase is the best studied and perhaps the most important mechanism of regulation of elongation rate. Since this phosphorylation is strictly Ca(2+)-dependent, and makes eEF-2 inactive in translation, this mechanism could explain how changes in the intracellular free Ca2+ concentration may regulate elongation rate. We also discuss some recent findings concerning elongation factors, such as the discovery of developmental stage-specific elongation factors and the regulated binding of eEF-1 alpha to cytoskeletal elements. Together, these observations underline the importance of the elongation stage of translation in the regulation of the cellular processes essential for normal cell life. PMID- 1855587 TI - How does protein synthesis give rise to the 3D-structure? AB - The recent experimental data on stages and kinetic intermediates in protein folding are reviewed. It is emphasized that these data are consistent with the 'framework model' proposed by the author in 1973. The model implies that protein folds by stage mechanism (secondary structure - molten) globule state - native state) in such a way that the results of previous stages are not reconsidered in subsequent ones. Arguments are presented that both these hypotheses and available experimental data do not contradict the assumption that native structures of at least small proteins are nevertheless under thermodynamic rather than kinetic control i.e. correspond to global minima of free energy. PMID- 1855588 TI - Protein export in prokaryotes and eukaryotes. Theme with variations. AB - Protein export in prokaryotes as well as in eukaryotes can be defined as protein transport across the plasma membrane. In both types of organisms there are various apparently ATP-dependent transport mechanisms which can be distinguished from one another and which show similarities when the prokaryotic mechanism is compared with the respective eukaryotic mechanism. First, one can distinguish between transport mechanisms which involve so-called signal or leader peptides and those which do not. The latter mechanisms seem to employ ATP-dependent transport systems which belong to the family of oligopeptide permeases and multiple drug resistance proteins. Second, in signal or leader peptide-dependent transport one can distinguish between transport mechanisms which involve ribonucleoparticles and those which employ molecular chaperones. Both mechanisms appear to converge at the level of ATP-dependent translocases. PMID- 1855589 TI - The cystatins: protein inhibitors of cysteine proteinases. AB - The last decade has witnessed enormous progress of protein inhibitors of cysteine proteinases concerning their structures, functions and evolutionary relationships. Although they differ in their molecular properties and biological distribution, they are structurally related proteins. All three inhibitory families, the stefins, the cystatins and the kininogens, are members of the same superfamily. Recently determined crystal structures of chicken cystatin and human stefin B established a new mechanism of interaction between cysteine proteinases and their inhibitors which is fundamentally different from the standard mechanism for serine proteinases and their inhibitors. PMID- 1855590 TI - Does ferredoxin I (Azotobacter) represent a novel class of DNA-binding proteins that regulate gene expression in response to cellular iron(II)? AB - Azotobacter vinelandii (Av) and chroococcum (Ac) ferredoxin I contain [3Fe-4S]1 + 0 and [4Fe-4S]2+1+ clusters, when isolated aerobically, which undergo one electron redox cycles at potentials of -460 +/- 10 mV (vs SHE) at pH 8.3 and -645 +/- 10 mV, respectively. The X-ray structure of Fd I (Av) reveals that the N terminal half of the polypeptide folds as a sandwich of beta-strands which enclose the iron-sulphur clusters. The C-terminal sequence contains an amphiphilic alpha-helix of four turns which lies on the surface of the beta barrel. Fd I (Av) controls expression of an unknown protein of Mr approximately 18,000. Fd I (Ac) will complex iron(II) avidly above pH approximately 8.0 only when the [3Fe-4S] cluster is reduced and provided that cellular nucleic acid is bound. Fd I (Ac) rigorously purified from nucleic acid does not undergo iron(II) uptake. These facts, together with recent evidence that the interconversion process [3Fe-4S]0 + Fe2+----[4Fe-4S]2+ in the iron-responsive element binding protein (IRE-BP) of eukaryotic cells is controlling protein expression at the level of mRNA [1991, Cell 64, 4771; 1991, Nucleic Acid Res. 19, 1739] leads to the following hypothesis. Fd I is a DNA-binding protein which interacts by single alpha-helix binding in the wide groove of DNA. The binding is regulated by iron(II) levels in the cell. The 7Fe form binds to DNA and represses gene expression. Only the DNA-bound form of the 7Fe Fd I will take up iron(II), not the form free in solution. Iron(II) becomes bound when the [3Fe-4S] cluster is reduced. The 8Fe Fd I thus generated no longer binds DNA and the gene is de repressed. Sequence comparisons and the crystal structure suggests that the two central turns of the alpha-helix are important elements of the DNA-recognition process and that residues Gln69 and Glu73, which lie on the outer surface of the helix, hydrogen-bond with specific base pairs. PMID- 1855591 TI - Protein secondary structure determination by NMR. Application with recombinant human cyclophilin. AB - It is a unique trait of the NMR method for protein structure determination that a description of the polypeptide secondary structure can be obtained at an early stage and quite independently of the complete structure calculation. In this paper the procedures used for secondary structure determination are reviewed and placed in perspective relative to the other steps in a complete three-dimensional structure determination. As an illustration the identification of the regular secondary structure elements in human cyclophilin is described. PMID- 1855592 TI - Signal transduction mechanism of interleukin 6 in cultured rat mesangial cells. AB - Interleukin 6 (IL-6) is one of the potent autocrine growth factors for mesangial cells. We investigated the signal transduction mechanism of IL-6 in cultured rat mesangial cells. IL-6 induced a transient increase of inositol 1,4,5 trisphosphate (Ins 1,4,5-P3) followed by a transient and sustained increase of intracellular calcium concentration, suggesting that IL-6 stimulates phosphoinositide turnover. IL-6 also stimulated prostaglandin E2 (PGE2) production. The IL-6-concentration dependency in PGE2 production was similar to that in Ins 1,4,5-P3 production. We concluded that the action of IL-6 on mesangial cells is exerted at least partially through the enhancement of phosphoinositide turnover and PGE2 production. PMID- 1855593 TI - Characterization and regulation of the expression of scyllatoxin (Leiurotoxin I) receptors in the human neuroblastoma cell line NB-OK 1. AB - 125I-[Tyr2]scyllatoxin allowed to label a single class of high-affinity receptors in membranes from the human neuroblastoma cell line NB-OK 1. The Kd of these receptors was 60 pM for scyllatoxin (Leiurotoxin I) and 20 pM for apamin and the Bmax was low (3.8 fmol/mg membrane protein). K+ increased toxin binding at low concentrations but exerted opposite effects at high concentrations. Ca2+, guanidinium and Na+ exerted only inhibitory effects on binding. Scyllatoxin binding sites were overexpressed 2.5-fold after a 24-h cell pretreatment with 2 mM butyrate. This effect was suppressed by cycloheximide. PMID- 1855595 TI - [Measuring the muscular strength of the tongue and the mimetic muscles surrounding the oral cavity]. PMID- 1855594 TI - [Open bite and its management]. AB - Morphological and functional symptoms of various varients of the open bite are reported on. The orthodontic treatment possibilities and, then, the surgical methods applicable after termination of jaw bone development are summarized. The functional disturbances have to be considered in case of both the conservative and the surgical treatment. A patient treated with a fixed device and an operated patient are presented. PMID- 1855596 TI - [Experience with the clinical use of HTR (hard tissue replacement) polymer. Sinus elevation, human histological studies]. AB - The HTR polymer was employed under clinical circumstances. Results supported that the HTR polymer may well be employed for bone replacement. The forming of the support tissue between the plastic granulums has been accompanied with biopsies. Though in some cases giant cell reaction of alien body type have been observed, yet this has never been of such degree that it would have impeded the reception of the stuff. According to the authors opinion after reinforcement of the lower wall of the facial cavity with HTR polymert in 8 to 10 months an enduring suitable support tissue is formed. PMID- 1855597 TI - [Incorrect technical terms in Hungarian dental terminology]. AB - The standpoint of the Hungarian Scientific Academy in case of medical orthography is described. Attention is called that anatomic denominations have to be concordant with the currently valid international nomenclature. Improper technical terms frequently occurring in dental papers and parlance are pointed out and the correct denominations are expounded. PMID- 1855598 TI - [Various stages of reduction in wisdom teeth. Dentition anomalies from the case load of a district dentist, 10]. AB - The isolated entire tooth group anomalies are discussed in connection with two cases. In the first case the lower and upper incisors are hypodontic whereas in the second case the hypodontia appears in the molar region. The interest of the latter case is increased by a microdont tooth which appeared in the place of the left upper seventh tooth. PMID- 1855599 TI - [Comparative measurements of right and left branches of the mandible]. AB - Eighteen pairs of mandible measures were evaluated according to sex on europide skulls coming from south-eastern Hungarian cemeteries of the X-XII., centuries in order to disclose possible measure differences between the left and right side. Only a single measure, the smallest sagittal diameter of the collume mandibulae showed significant difference between both sides which was observed in both groups of men and women. The percentual relative frequencies according to which the 18 measures were equal on the left and right side (within 1 millimeter measuring error) changed between 39.9% and 82.0% (average 58.6%) with men, and between 45.9% and 83.2% (average 59.6%) with women. The examined measures proved to be greater on the right side by 3.2% with men and by 4.6% with women. PMID- 1855600 TI - [Skin test series for the determination of contact allergy to dental materials]. PMID- 1855601 TI - [Hypodontia in isolated groups of teeth. Dental anomalies from the case load of a district dentist, 11]. AB - The isolated entire tooth group anomalies are discussed in connection with cases. In the first the lower and upper incisors are hypodontic whereas in the second case the hypodontia appears in the molar region. The interest of the latter case is inereased byamicrodont tottht which appeared in the place of the left upper seventh tooth. PMID- 1855602 TI - [Questions of principle and practice concerning the use of Diakor aluminum oxide in bioceramical oral endosseous implantation. III. Surgical intervention]. AB - The osseointegration desired in interest of lasting success may be obtained but by means of an aseptic atraumatic operational technique which ensures the primary stability of the implant. It is pointed out that the infection free wound healing plays a decisive role in the lasting stability of the implant also the surgical planning and the method of avoiding complications are described. PMID- 1855603 TI - Pregnancies and offspring in survivors of acute lymphoid leukemia and lymphoma. AB - Since few data on the reproductive outlook of patients successfully treated for lymphoproliferative disease are available, further experiences on the pregnancy outcome and offspring follow-up of 12 women treated for acute lymphoid leukemia and 7 women treated for malignant lymphoma are reported. Of the 20 pregnancies of leukemic patients in remission, 14 ended in live births, one in spontaneous abortion, and 5 in elective abortions among which one was performed during relapse. One minor (hip dysplasia) and one major birth defect (Apert syndrome) were seen. The Apert syndrome baby is considered as a new mutation. Of the 9 pregnancies of lymphoma patients 5 ended in normal births and 4 in elective abortions. Neither relapse nor malformation was encountered. One leukemic patient had gestational edema and one lymphoma patient had puerperal thrombophlebitis of lower extremity. The offspring of the above patients appropriately developed and had no complication except for one with cephalhematoma and for another one with epilepsy attributed to birth injury. PMID- 1855604 TI - Preinduction cervical assessment by Bishop's score and transvaginal ultrasound. AB - In this pilot study, 50 patients underwent preinduction cervical assessment by digital Bishop Score (BS) and transvaginal ultrasonography. The BS was lower in 7 patients requiring caesarean section than in 43 delivered vaginally (P = 0.017). Of seven ultrasound parameters examined, six (cervical length, width, dilatation, application and position and lower segment thickness) were similar in both groups. Cervical angle, however, was more acute in those delivered abdominally than vaginally (median = 60 degrees and 90 degrees, respectively, P = 0.002). Posterior cervical angle was more accurate than BS in predicting vaginal delivery (Kappa = 0.48 versus 0.21). Patient discomfort was significantly less with transvaginal ultrasound than digital examination. Combining posterior cervical angle greater than 70 degrees and BS greater than 5 yielded the best accuracy in predicting successful induction of labour (sensitivity = 88%, specificity = 100%, Kappa = 0.68). PMID- 1855605 TI - Length of the human umbilical cord in multiple pregnancy. AB - The factors controlling the length of the human umbilical cord are uncertain. In the generally accepted 'tension theory', the length of the umbilical cord is proposed to increase the tensile force on it in the uterus. The greatest tensile force is supposed to be fetal movement. If this is so, the length of the umbilical cord should be shorter in multiple pregnancy than in single pregnancy. To examine this possibility we measured the umbilical cord lengths in 3314 singleton births, 82 twins births (164 infants), and 11 triplet or quadruplet births (35 infants). The cord lengths in multiple pregnancies (twins 51.3 cm, triplets and quadruplets 50.1 cm) tended to be shorter than that in singleton pregnancies (57.2 cm). However, no significant difference was found in the ratio of the umbilical cord length to the infant body weight in these groups. Therefore, we conclude that an important factor in determining the cord length is the size of the infant. PMID- 1855606 TI - High blood pressure during pregnancy and working conditions among hospital personnel. AB - The relationship between working conditions and high blood pressure during pregnancy was analysed in a sample of 621 women hospital employees in the Paris region over the period 1979-1981. Data were collected by interviews during the routine medical visit at the end of postnatal leave. Women who had to work standing up for extended periods of time, who had to carry heavy loads or who had to perform heavy cleaning tasks had high blood pressure during their pregnancy more often than women not exposed to these working conditions. The accumulation of two out of the three or these three working conditions by the same woman was strongly related to high blood pressure. This relation remained significant when other risk factors of hypertension, such as age, parity, corpulence and tobacco use, were taken into account in a multiple logistic regression. PMID- 1855607 TI - Intrapartum chemoprophylaxis of early-onset group B streptococcal disease. AB - A randomized study in 121 pregnant women carrier of group B streptococci is undertaken in order to assess the administration of 500 mg of intrapartum ampicillin intravenously to interrupt mother-to-fetus group B streptococcal transmission. In the prophylaxis group there was a significant reduction in neonatal colonization (3.7 vs. 42.9%) and in severe neonatal colonization (0 vs. 25%). There was no case of group B streptococcal sepsis in the prophylaxis group compared to 4.6% (3 cases) in the control group (P greater than 0.05). Clinically infected newborns represented 3.3% in the prophylaxis group vs. 13.8% in the control group. When the organism was isolated during delivery in the vagina or amniotic fluid, prophylaxis was quickly followed by second negative cultures. Ampicillin levels in the amniotic fluid were detected early, and they increased significantly till the third hour. Bactericidal levels in the umbilical cord were detected in 60% of newborns. All these findings support the usefulness of ampicillin prophylaxis in the prevention of early-onset group B streptococcal sepsis. PMID- 1855608 TI - Intra-uterine hematoma in pregnancy. AB - In 60 patients with a live fetus and an intra-uterine hematoma (IUH) proven by ultrasonic scanning the outcome of pregnancy was spontaneous abortion in 12% and premature delivery in 10%. No correlation between the outcome of the pregnancy and the maximum size of the hematoma or the week of detection was found. A subplacentar localization of the hematoma was associated with a higher, but not statistically significant, incidence of spontaneous abortion than a subchorionic localization. Spontaneous abortion most often occurred in the first weeks after the formation of the hematoma. PMID- 1855609 TI - Invasive papillary serous adenocarcinoma of the endocervix in pregnancy; a case report. AB - A case of invasive papillary serous adenocarcinoma of the endocervix in pregnancy is described. The pure papillary pattern appears rarely, and to the best of our knowledge has never been described previously in pregnancy. PMID- 1855610 TI - Working toward a restraint-free environment. PMID- 1855611 TI - Maintaining a smoke-free psychiatric ward. PMID- 1855612 TI - Extra-Mural: the hospital without walls. PMID- 1855613 TI - Home care unites for a new decade. PMID- 1855614 TI - Codeine: developmental toxicity in hamsters and mice. AB - Timed-pregnant LVG Syrian hamsters and Swiss CD-1 mice were dosed orally twice daily (b.i.d.) with codeine in water on Gestational Days (gd) 5-13 (0, 10, 50, or 150 mg/kg, b.i.d.--hamsters) or 6-15 (0, 37.5, 75, 150, or 300 mg/kg, b.i.d.- mice). Dams were necropsied on gd 14 (hamsters) or 17 (mice), and fetuses were weighed, sexed, and examined for external, visceral, and skeletal malformations. No maternal deaths were observed in hamsters, while 19% of the pregnant mice in the high-dose group died. Maternal weight gain (gestational and treatment periods) and gravid uterine weights were significantly depressed in hamsters (150 mg/kg, b.i.d.) and in mice (300 mg/kg, b.i.d.). However, the corrected weight gain for both species, although decreased, was not significantly different from that of the controls. In both species, maternal liver weights (relative) were significantly increased in the high-dose groups. There were increases in the percentage resorptions per pregnant dam and in the proportion of litters with 100% resorptions in the high-dose groups of both species. Considering only live litters, the number of live fetuses per litter and the sex ratio were unaffected in both species. Mean fetal body weights were also significantly decreased in the 50 and 150 mg/kg, b.i.d. (hamsters), and the 150 and 300 mg/kg, b.i.d. (mice), groups. The no-observed-adverse-effect levels (NOAELs) for developmental toxicity were 10 (hamsters) and 75 (mice) mg/kg, b.i.d., whereas the NOAELs for maternal toxicity were 50 (hamsters) and 150 (mice) mg/kg, b.i.d. The predominant structural malformation in hamsters was meningoencephalocele (high-dose group only), affecting 3% of fetuses and 19% of litters (neither statistically significant). Codeine did not induce any increase in structural malformations in mice. Thus, codeine produced developmental toxicity (as indicated by decreased fetal body weight) at doses below those producing maternal toxicity in both hamsters and mice. In the hamster, the more sensitive species to codeine developmental toxicity, effects were observed at a total daily dose of 100 mg/kg, which is only 11 times the maximum human therapeutic oral dose. PMID- 1855615 TI - Developmental toxicity of dimethylacetamide by inhalation in the rat. AB - Dimethylacetamide (DMAC) is a widely used industrial solvent. It has been reported to be teratogenic when given to rats by injection or following dermal application. Most of these studies employed large single doses and did not examine both the fetal and the maternal response. In this study, groups of pregnant Crl:CD rats were exposed to 32, 100, or 282 ppm DMAC by inhalation for 6 hr/day from Days 6 through 15 of gestation (day on which copulation plug was detected was termed Day 1G). A control group of chambered pregnant rats was exposed simultaneously to air only. All female rats were euthanized on Day 21G. At 282 ppm, both maternal weight gain during the exposure period and fetal weight were significantly decreased and accompanied by a significant dose-response trend. These effects were not seen in rats inhaling either 32 or 100 ppm. Fetal resorptions were not increased in any of the groups exposed to DMAC. Fetal incidences of external, visceral, or skeletal variations and malformations were similar between the test and control groups. Therefore, both fetal and maternal toxicity were noted at 282 ppm and the no-observed adverse-effect level under these experimental conditions was 100 ppm for both the dam and the conceptus. DMAC was not demonstrated to produce malformations in the rat fetus even at a level that was toxic to the dam. PMID- 1855616 TI - An optimization strategy for a biokinetic model of inhaled radionuclides. AB - Models for material disposition and dosimetry involve predictions of the biokinetics of the material among compartments representing organs and tissues in the body. Because of a lack of human data for most toxicants, many of the basic data are derived by modeling the results obtained from studies using laboratory animals. Such a biomathematical model is usually developed by adjusting the model parameters to make the model predictions match the measured retention and excretion data visually. The fitting process can be very time-consuming for a complicated model, and visual model selections may be subjective and easily biased by the scale or the data used. Due to the development of computerized optimization methods, manual fitting could benefit from an automated process. However, for a complicated model, an automated process without an optimization strategy will not be efficient, and may not produce fruitful results. In this paper, procedures for, and implementation of, an optimization strategy for a complicated mathematical model is demonstrated by optimizing a biokinetic model for 144Ce in fused aluminosilicate particles inhaled by beagle dogs. The optimized results using SimuSolv were compared to manual fitting results obtained previously using the model simulation software GASP. Also, statistical criteria provided by SimuSolv, such as likelihood function values, were used to help or verify visual model selections. PMID- 1855617 TI - Assessment of mitochondrial membrane potential as an indicator of cytotoxicity. AB - Mechanistically based short-term in vitro tests to evaluate the relative cytotoxicity of of chemicals will complement in vitro genotoxicity testing during the initial phases of toxicity evaluation as well as provide information on the cellular site of action for chemicals found to be toxic in animals. The objective of this study was to characterize a procedure for evaluating mitochondrial membrane potential, an integral component of cellular energy homeostasis and normal cellular function, as an in vitro indicator of chemically induced cytotoxicity. Rhodamine 123, a cationic fluorescent dye whose mitochondrial fluorescence intensity decreases quantitatively in response to dissipation of mitochondrial transmembrane potential, was used to evaluate disturbances in mitochondrial membrane potential. Cultured rat liver epithelial cells (WB cell line) or human skin fibroblasts (MSU-2 cell line) treated with the oxidative phosphorylation uncoupler 2,4-dinitrophenol (DNP) or the cytochrome oxidase inhibitor sodium azide were used to characterize the system. In addition, acetaldehyde, which has been reported to damage the plasma membrane, but not the mitochondrial membrane, was used to demonstrate the specificity of this assay system. Mitochondrial membrane potential was not significantly affected by the cell culture density, as long as the cells were in the logarithmic phase of growth. The stage of the cell cycle influenced the mitochondrial membrane potential in human skin fibroblasts (highest in late G1-early S) but not in rat liver cells. DNP and sodium azide significantly (p less than 0.01) reduced the mitochondrial membrane potential in both cell lines compared to untreated cells, while acetaldehyde did not reduce the mitochondrial membrane potential in either cell line. This assay provides a tool for evaluating the effect of chemical treatments on mitochondrial membrane potential, as well as an indicator of cytotoxicity which does not require the use of animals. PMID- 1855619 TI - Differences in the mode of lethality produced through intravenous and oral administration of organophosphorus insecticides in rats. AB - This study was undertaken to investigate the possibility that mechanisms other than cholinesterase (ChE) inhibition account for the acute toxicity of organophosphorus insecticide. Both the P = O type insecticide (direct ChE inhibitors: chlorfenvinphos and dichlorvos) and the P = S type insecticide (indirect ChE inhibitors: diazinon and fenthion) were employed. Rats treated with lethal doses of intravenous and oral P = O type insecticides and oral P = S type insecticides exhibited typical signs of anti-ChE poisoning along with marked inhibition of brain and erythrocyte ChE activity. In contrast, rats given lethal doses of intravenous P = S type insecticides exhibited tonic convulsions and opisthotonos, with only slight inhibition of ChE activities. When P = O type insecticides were intravenously administered to anesthetized and conscious rats, animals exhibited typical anti-ChE poisoning signs in cardiorespiration: hypertension and apnea which were antagonized by atropine. After administration of lethal doses of P = O type insecticides, breathing disappeared before the cessation of heart beats. Rats receiving lethal doses of intravenous P = S type insecticides did not show hypertension, but exhibited transient cessation of breathing and heart beats. Breathing was observed after the disappearance of heart beats. The electroencephalogram (EEG) was characterized by spike and wave complexes. The EEG and cardiorespiratory changes were not antagonized by atropine. It was concluded that lethality following intravenous P = S type insecticides may be independent of ChE inhibition. PMID- 1855618 TI - Comparison of cholinergic and neuromuscular toxicity following acute exposure to sarin and VX in rat. AB - Male Sprague-Dawley rats injected with a sublethal sc dosage of 110 micrograms/kg of sarin (isopropyl methylphosphonofluoridate), or 12 micrograms/kg of VX (S-(2 diisopropylaminoethyl) O-ethyl methylphosphonothioate), developed severe toxic signs within 5-15 min after sarin and 20-50 min after VX lasting for 5 to 7 hr. Myonecrotic lesions were seen in soleus and diaphragm muscles within 1 hr. A maximum number of lesions had developed after 24 hr, and lesions were also present in extensor digitorum longus (EDL) at this time. Regeneration of muscle fibers was slow since lesions were still evident past 7 days of treatment. Within 1 hr following VX, AChE activity was reduced to 8, 12, and 17% of control activity in soleus, diaphragm, and EDL, respectively, whereas with sarin the enzyme activity was reduced to 23, 48, and 82% of control. A still greater inhibition was seen 24 hr after sarin when AChE activity was reduced to 19, 13, and 43% in these muscles. In skeletal muscles the different molecular forms of AChE, such as 16 S, 12 S, 10 S, and 4 S vary in location and functional importance with the 16 S form highly concentrated at the neuromuscular junction. All forms in a given muscle were equally sensitive to the inhibitors. In EDL, sarin was the least effective in reducing AChE or its molecular forms. In the brain structures (cortex, brain stem, striatum, and hippocampus), AChE activity was reduced to 1-6% of control by sarin and VX with the exception that following VX striatal AChE was reduced to only 41% of control activity. AChE activity in the brain cortex following either of the agents was maximally affected (1%). A slow but significant recovery of brain AChE was evident after 24 hr and more so after Day 7. Butyrylcholinesterase (BuChE) activity was less sensitive to inhibition by both inhibitors compared to AChE activity and showed a rapid recovery. Based on the equitoxic doses (toxic signs of similar magnitude), VX was found to be 10 times more toxic than sarin. The mechanisms of this disparity may be due to differences in rate of uptake, circulation, susceptibility to hydrolysis, and reactivity with nonspecific binding sites. PMID- 1855620 TI - Trihexyphenidyl enhances physostigmine prophylaxis against soman poisoning in guinea pigs. AB - The protective effects of simultaneous and continuous administration of physostigmine and trihexyphenidyl against soman-induced toxicity were studied in guinea pigs. Not only did trihexyphenidyl reduce physostigmine-induced toxicity when it was administered continuously to the animals along with physostigmine, the combination afforded greater protection from soman lethality than did either agent administered alone. The combination pretreatment also gave better protection against soman-induced body weight loss and decreased water consumption and attenuated the down-regulation of cholinergic receptors which occurred when physostigmine alone was used. The onsets of other soman-induced toxicity signs were delayed significantly by the combination pretreatment regimen. These results suggest that simultaneous administration of the combination of physostigmine and trihexyphenidyl may be more useful than physostigmine alone as prophylaxis against soman poisoning. PMID- 1855621 TI - A two-generation reproduction study in rats receiving diets containing hexamethylenediamine. AB - Rats received diets containing average daily doses of 0, 50, 150, and 500 mg/kg/day of hexamethylenediamine over two generations. Although no treatment related mortality was observed in any of the groups, the weight gain of adults and pups was slightly reduced in the high dose group. While the litter size was also slightly reduced at birth in the high dose group, there was no adverse effect on survival during lactation in any of the treated groups. Thus, the dietary administration of up to 150 mg/kg/day of hexamethylenediamine over two generations did not adversely affect reproduction or fertility in rats. PMID- 1855622 TI - Validation of protocols for assessing early pregnancy failure in the rat: clomiphene citrate. AB - A battery of protocols for the assessment of maternally mediated toxicity during early pregnancy in the rat is being evaluated for its utility in detecting and defining mechanisms of early pregnancy failure. In this report, clomiphene citrate (CC), an estrogen agonist/antagonist, was used as a model compound in this evaluation process. The protocols involve dosing rats with CC during, and evaluation of multiple endpoints following, (a) the first 8 days of pregnancy; (b) early pseudopregnancy, accompanied by decidual induction; and (c) the pre- and postimplantation intervals of early pregnancy. In addition, the effect of CC on embryo transport rate was assessed. Eight days of dosing with CC during early pregnancy produced a dose-dependent reduction in the number of implantation sites seen on Day 9, concomitant with alterations in maternal hormonal parameters. No effect on the decidual cell response was found, indicating that the mechanism of fertility reduction was not mediated via compromised uterine decidualization. The preimplantation period was highly vulnerable to the toxic effects of CC while no postimplantation resorptions were seen. When embryo transport rate was measured, a statistically significant embryo transport rate acceleration was detected, but this was insufficient to account for all of the observed preimplantation loss. The data suggest an effect of CC on embryo viability, on the embryo's ability to implant, or on the reproductive tract resulting in compromised embryo survival as the potential mechanism(s) mediating CC-induced early pregnancy failure. The battery of protocols was thus successful in identifying CC as a reproductive toxicant and in elucidating the causes of the observed early pregnancy failure. PMID- 1855623 TI - Percutaneous absorption/metabolism of phenanthrene in the hairless guinea pig: comparison of in vitro and in vivo results. AB - The in vitro and in vivo percutaneous absorption/metabolism of phenanthrene was investigated in hairless guinea pigs. Flow-through diffusion cells and Hepes buffered Hanks' balanced salt solution (HHBSS) as receptor fluid were used in the in vitro system. When phenanthrene was applied to excised guinea pig skin mounted on the cells at dose levels of 6.6 and 15.2 micrograms/cm2, 89.7 and 79.1% of the administered doses were respectively absorbed into the skin and receptor fluids during a 24-hr perfusion period. These results are consistent with the in vivo data which showed approximately 80% absorption over the same period of time. Phenanthrene was metabolized in vitro into phenanthrene 9,10-dihydrodiol, 3,4 dihydrodiol, 1,2-dihydrodiol, and traces of hydroxy phenanthrenes. Of the materials absorbed in vitro, 92% was the parent compound and 7% the dihydrodiol metabolites. When a nonviable in vitro system was used, 68% of the applied 15.2 micrograms/cm2 dose was absorbed. Data from the present study demonstrate that the in vitro system is a good model for predicting in vivo percutaneous absorption of phenanthrene, and that penetration of phenanthrene through the skin is controlled more by the passive rate of diffusion than by metabolism. PMID- 1855624 TI - An initiation-promotion assay in rat liver as a potential complement to the 2 year carcinogenesis bioassay. AB - Several pharmaceutical agents, manufacturing chemicals, and environmental contaminants were found to act primarily as promoting agents in an initiation promotion paradigm. The phenotypic distribution of four enzyme markers--placental glutathione-S-transferase (PGST), gamma-glutamyl transpeptidase (GGT), canalicular ATPase (ATPase), and glucose-6-phosphatase (G6Pase)--was analyzed in altered hepatic foci (AHF) by quantitative stereology. The number and volume distribution of AHF were determined for each promoter tested. For phenobarbital and 2,3,7,8-tetrachloro-p-dioxin, PGST and GGT together scored 100% of the AHF; for 1-(phenylazo)-2-naphthol (CI solvent yellow 14) and chlorendic acid, PGST alone marked 90% of the AHF; after chronic administration of WY-14,643, ATP and G6Pase were the predominant markers. In rats fed tamoxifen, G6P scored more than half of the AHF. Differences in the number of AHF promoted by each of these agents and in their phenotypic distributions may reflect the differentially responsive nature of individual initiated hepatocytes to the action of specific promoters. Since the chronic bioassay of suspected carcinogens does not allow one to differentiate between weak complete carcinogens and those carcinogenic agents that act in a reversible manner to promote the growth of previously initiated cells, the partial hepatectomy, altered-hepatic-focus model of cancer development is proposed as a supplement to the chronic bioassay for the identification of those carcinogenic agents that are primarily, if not exclusively, promoting agents in rat liver. PMID- 1855625 TI - Pharmacokinetics and pharmacodynamics of oximes in unanesthetized pigs. AB - The pharmacokinetics and cardiovascular pharmacodynamics of two oximes were studied in unanesthetized pigs. Effects of 2-[(hydroxyimino)methyl]-1 methylpyridinium chloride (pralidoxime chloride; 2-PAM Cl; 50 mumol/kg) were compared with those of 1,1-methylene bis[4(hydroxyiminomethyl) pyridinium] dichloride (methoxime; MMB-4; 100 mumol/kg). Cardiopulmonary parameters were monitored and plasma concentrations of oximes were determined from arterial blood samples taken at intervals over a period of 5 hr postinjection. Plasma concentrations for both oximes were fitted to standard pharmacokinetic models using the computer program PCNONLIN. Average pharmacokinetic parameters were determined for each oxime. Only mild to moderate physiological side effects were detected following intramuscular administration. 2-PAM Cl was more rapidly absorbed and distributed in the blood than MMB-4. Although the latter had a slight lag time to attain detectable levels in the blood, retention time was longer than that of 2-PAM Cl. PMID- 1855626 TI - Rhodanese and sodium thiosulfate encapsulated in mouse carrier erythrocytes. II. In vivo survivability and alterations in physiologic and morphologic characteristics. AB - Biodegradable drug carrier mechanisms were employed in drug antagonism studies. Prior studies indicated that erythrocytes containing encapsulated rhodanese and sodium thiosulfate metabolized cyanide to thiocyanate in vitro. Studies were conducted to investigate the properties of these sulfurtransferase-loaded red blood cells in vivo by administering the carrier red blood cells intravenously. Approximately 40 to 50% of the cells were eliminated within the first few hours while the remaining loaded erythrocytes persisted in the circulation. The present studies were initiated to investigate the characteristics of the disposition of the loaded erythrocytes and to examine differences in the properties between carrier and noncarrier erythrocytes. Also, the disposition and viability of the erythrocytes in vivo were studied with relation to various biochemical, physiological, and morphological properties. These studies indicated that the carrier erythrocytes had a smaller cell volume and were more susceptible to hemolysis than normal erythrocytes. Morphologic studies by electron microscopy indicated that extensive morphologic changes occurred during the procedures after hypotonic dialysis, isotonicity adjustment, and resealing were completed. Differences were noted between those cells that were only resealed and those cells that were also subjected to annealing. The morphologic characteristics of most of the cells were restored to the "normal" morphologic appearance only after annealing. Annealed erythrocytes' in vivo survivability was correlated with the physical properties of these cells. PMID- 1855627 TI - Bis(2-methoxyethyl) ether: metabolism and embryonic disposition of a developmental toxicant in the pregnant CD-1 mouse. AB - An embryotoxic oral dose of bis(2-methoxyethyl) ether (DGDME), 3.73 mmol/kg body wt (500 mg/kg), administered on the 11th day of gestation to pregnant CD-1 mice was metabolized predominantly by O-demethylation to 2-(2-methoxyethoxy)ethanol with subsequent oxidation to (2-methoxyethoxy)acetic acid. Urinary excretion of this metabolite over 48 hr amounted to 63 +/- 2% of the dose. A smaller percentage of the administered dose was metabolized at the central ether linkage to produce 2-methoxyethanol, which was further metabolized by alcohol dehydrogenase to methoxyacetic acid. Urinary excretion of methoxyacetic acid, a potent developmental toxicant, amounted to 28 +/- 1% of the administered dose by 48 hr and was the second most prominent urinary metabolite. Unchanged DGDME and methoxyacetic acid were detected in the embryonic tissues from these animals, and embryos harvested after the initial 6-hr period showed detectable amounts of only methoxyacetic acid. The average amount of methoxyacetic acid per embryo was calculated to be 1.5 +/- 1.0 mumol (5.9 mmol/kg body wt) at the 6-hr termination time. This finding suggests that the reported teratogenic effects of DGDME are due to methoxyacetic acid formed, either in the fetus or by hepatic metabolism in the dam with subsequent distribution to the embryonic tissue. These results suggest that such developmental toxicity may occur with structurally similar aprotic ethylene glycol ethers in which metabolic O-dearylation would yield 2 methoxy-ethanol. PMID- 1855628 TI - Refinement of long-term toxicity and carcinogenesis studies. PMID- 1855629 TI - Fluoride-releasing liners: in vitro recurrent caries. PMID- 1855630 TI - A long-term provisional restoration. PMID- 1855631 TI - Dental erosion caused by cola beverages. PMID- 1855632 TI - Porcelain onlays in restoration of vertical dimension. PMID- 1855634 TI - Integrity: what do you want it to be? PMID- 1855633 TI - Erosive lichen planus exacerbated by full-metal restorations. PMID- 1855635 TI - Burning mouth syndrome. PMID- 1855636 TI - The effect of intraligamentary injections on diseased periodontiums in dogs. PMID- 1855637 TI - A patient instruction guide used in treating ANUG. PMID- 1855638 TI - Pulp testing while avoiding dangers of infection and cross-contamination. PMID- 1855639 TI - Diffuse discoloration of teeth. PMID- 1855640 TI - Unusual maxillary lateral incisors. PMID- 1855641 TI - Cyclic juvenile hormone biosynthesis in the cockroach, Blattella germanica: effects of ovariectomy and corpus allatum denervation. AB - The corpora allata (CA) of ovariectomized adult Blattella germanica females exhibited delayed but high rates of juvenile hormone biosynthesis in vitro. Using the onset of sexual receptivity as a probe of the degree of CA activation in females, we demonstrated at least one cycle of CA activity in the experimentally synchronized ovariectomized females. Following their activation, the CA exhibited a partial and transient decline in activity, but in contrast to the CA of intact females, this decline was not accompanied by a regression in CA volume. CA of intact and ovariectomized females that were denervated from the brain were activated, but the subsequent decline in CA activity at the end of the cycle was prevented in ovariectomized females. The presence of an egg-case suppressed the reactivation of the inactive CA in intact females but not in CA-denervated females. We conclude that activation of the CA in B. germanica is not dependent upon either the presence of the ovary or intact nervous connections between the CA and the brain. The brain exerts a partial inhibition on CA activity through intact nerves which is relieved (by disinhibition) in the presence of a young ovary but is enhanced and sustained in the presence of the egg-case. Inhibition of the CA also occurs independently of nervous connections with the brain through factors that originate in the mature ovary and affect both CA activity and morphology. PMID- 1855642 TI - Kinetic studies of growth hormone and prolactin during adaptation of coho salmon, Oncorhynchus kisutch, to different salinities. AB - The kinetics of growth hormone (GH) and prolactin (PRL) in coho salmon (Oncorhynchus kisutch) transferred from fresh water (FW) to seawater (SW) and vice versa were examined to help clarify the osmoregulatory roles of the two hormones during periods of migration to different salinities. Chum salmon GH or PRL was administered by a single injection intraarterially, and metabolic clearance rate (MCR) and secretion rate (SR) of injected hormones were calculated from the disappearance of the hormones from the plasma. When coho salmon smolts were acclimated to SW, MCR, SR, and plasma level of GH in SW-adapted (2-3 weeks) fish were twice as great as those in fish in FW. On the other hand, there was no difference in the kinetics of GH between the adult coho salmon in SW and those adapted to FW (2-3 weeks). The transfer of the adult coho salmon from SW to FW was followed after 2 days by a rise in plasma level and SR of PRL, which tended to stay at high levels after 2-3 weeks. The MCR of PRL increased significantly after 2-3 weeks in FW. These results support the likelihood of an important role of GH in SW adaptation and of PRL in FW adaptation in coho salmon. PMID- 1855643 TI - Estradiol-induced vitellogenin gene expression in a teleost fish, Oreochromis aureus. AB - Vitellogenesis presents a versatile model for the study of hormone-induced gene expression. We report here the effects of estradiol-17 beta-propionate on vitellogenin gene expression in male Oreochromis aureus, a teleost fish. Vitellogenin mRNA of 6500 nucleotides has been elucidated from the livers of female and estradiol-treated male O. aureus. By hybridization with a specific O. aureus cDNA probe, the vitellogenin mRNA transcript was detected as early as 1 hr following primary and secondary estradiol-stimulations, although for the latter, the rate of accumulation of vitellogenin-specific mRNA was 20-fold higher. The vitellogenin mRNA peaked at 72 and 48 hr, respectively, for primary and secondary stimulations. At the translational level, the increase in plasma vitellogenin was further enhanced during the secondary stimulation. There was a distinct shift in the peak of plasma vitellogenin from Day 14 in the primary induction to Day 3 in the secondary stimulation. The plasma vitellogenin presented in two forms, 300 and 500 kDa, both of which were immunologically confirmed by Western blot analysis to be vitellogenin proteins. PMID- 1855644 TI - Effect of various alanine analogues on the L-alanine-adding enzyme from Escherichia coli. AB - An extract from Escherichia coli containing the L-alanine-adding enzyme with a high specific activity was prepared. Several compounds structurally related to L alanine were tested as inhibitors of this activity. Intact amino and carboxyl groups were necessary for an interaction with the enzyme. Certain halogenated (haloalanines) or unsaturated (L-vinylglycine, L-propargylglycine, 3-cyano-L alanine) amino acids were good inhibitors. Radioactive glycine, serine and 1 aminoethylphosphonic acid were tested as substrates. Whereas glycine or L-serine gave rise to the formation of the corresponding nucleotide product, no synthesis of UDP-N-acetylmuramyl-L-1-aminoethylphosphonic acid could be detected. PMID- 1855645 TI - Differences between the LPS cores in adherent and non-adherent strains of enteropathogenic Escherichia coli 0119. AB - Adherent enteropathogenic Escherichia coli 0119 strains had a larger lipopolysaccharide core than non-adherent strains, although the O-chains were identical. The core from the non-adherent strain 19392 contained five hexose residues in the outer region, with three L-glycero-D-manno-heptose residues and 3 deoxy-D-manno-octulosonic acid (KDO) in the inner region. The core of adherent strain JCP88 had an atypical structure consisting of six hexose residues, KDO, and equimolar amounts of L-glycero-D-manno-heptose and D-glycero-D-manno-heptose. The core of a rough JCP88 mutant resembled an incomplete 19392 core. PMID- 1855646 TI - Detection of heat-stable enterotoxin in a cholera toxin gene-positive strain of Vibrio cholerae O1. AB - DNA colony hybridization with a polynucleotide clonal DNA probe for heat-stable enterotoxin of Vibrio cholerae non-O1 (NAG-ST) was used to screen 197 isolates of V. cholerae O1. Under stringent hybridizing and washing conditions, one strain (GP156) reacted with the probe. The concentrated supernatant from V. cholerae O1 GP156, heated at 100 degrees C for 5 min, elicited fluid accumulation in the suckling mice and that could be completely neutralized by an anti-NAG-ST monoclonal antibody (mAb2F). The preparation from V. cholerae O1 GP156 also inhibited the binding of mAb2F to NAG-ST in a competitive ELISA. V. cholerae O1 GP156 was confirmed to possess a gene encoding cholera toxin (CT). These results indicate that a heat-stable enterotoxin is produced by certain strains of CT producing V. cholerae O1. PMID- 1855647 TI - Establishment of Eubacterium cellulosolvens in the digestive tract of axenic and meroxenic mice: influence of feed cellulose content. AB - The cellulolytic bacterial species present in the caecum and colon contents of conventionally reared mature mice did not become established in the digestive tract when inoculated to axenic mice, whatever the size of the inoculum or the cellulose content of the diet. The cellulolytic bacterium Eubacterium cellulosolvens SC 10 isolated from mouse digestive flora was unable to become established in the digestive tract of axenic mice whatever the cellulose content of the diet; it requires a feed rich in cellulose and a highly diversified microflora. PMID- 1855648 TI - Murine monoclonal antibodies reactive with staphylococcal enterotoxins A, B, C2, D, and E. AB - By fusion of mouse spleen cells immunized with five different staphylococcal enterotoxins (SEA, SEB, SEC2, SED, and SEE) with myeloma cells, we obtained 15 hybridomas producing monoclonal antibodies (mAbs). Four mAbs were reactive with both SEA and SEE, whereas 8 mAbs were reactive with SEB and SEC2. One mAb reacted with SEA, SED, and SEE. The other two mAbs were found to be reactive with all five serotypes of SEs. The mAbs specific for five serotypes of SEs were found to be most reactive with SED, reactive with SEA, and slightly less reactive with SEB, SEC2, and SEE. Those mAbs with specificities for all serotypes of SEs may be valuable to prepare immunoadsorbent(s) for isolation of SEs and to detect SEs in foods and clinical specimens involved in outbreaks of staphylococcal food poisoning. PMID- 1855649 TI - Candida albicans and three other Candida species contain an elongation factor structurally and functionally analogous to elongation factor 3. AB - A cell-free poly(U)-dependent translation elongation system from Candida albicans is ATP-dependent due to the presence of an elongation factor 3 (EF3)-like activity. Saccharomyces cerevisiae ribosomes added to a C. albicans postribosomal supernatant (PRS) supported poly(U)-dependent elongation, suggesting that the C. albicans lysate contained a soluble translation factor functionally analogous to the S. cerevisiae translation factor EF-3. The presence of EF-3 in C. albicans was confirmed by Western blotting using an antibody raised against S. cerevisiae EF-3. This antibody was also used to screen a selection of Candida species, all of which possessed EF-3 with molecular mass in the range of 110-130 kDa. PMID- 1855650 TI - Enterococcus sulfureus, a new yellow-pigmented Enterococcus species. PMID- 1855651 TI - Identification of contemporary plasmid virulence genes in ancestral isolates of Salmonella enteritidis and Salmonella typhimurium. AB - Six epidemiologically distinct ancestral strains of Salmonella enteritidis and 5 of S. typhimurium from the pre-antibiotic era were examined for plasmid content, and for presence of plasmid genes implicated in mouse-virulence. Five sizes of plasmid were detected in S. enteritidis varying from 1 to 60 MDa. Two sizes of plasmid were found in S. typhimurium, 28 and 60 MDa. Plasmids of the same size were not common to both serovars. The HindIII restriction patterns of 3 of the ancestral S. enteritidis plasmids were identical to the modern 38 MDa plasmid, while all contained identical bands of 3.5, 2.7 and 1.9 kb. All the 60-MDa S. typhimurium plasmids, ancestral and contemporary, had an identical restriction pattern. Three different sized S. enteritidis plasmids and one size S. typhimurium plasmid contained a 3.5-kb DNA fragment carrying the virulence locus VirA. The VirB virulence locus was located on a 2.7-kb DNA fragment in S. enteritidis and on a 2.5-kb fragment in S. typhimurium. Both loci were precisely conserved between the ancestral strains and the modern representatives of both serovars. PMID- 1855652 TI - Chitin content and chitin synthase activity as indicators of the growth of three different anaerobic rumen fungi. AB - Growth of three different anaerobic rumen fungi Neocallimastix frontalis, Piromonas communis and Sphaeromonas communis was assessed in vitro at regular intervals by measurements of protein and chitin content and of chitin synthase activity of the cell free extracts. Similar trends and a comparable amount of protein and chitin were observed in the three species. However, chitin synthase activity was higher in S. communis and contrary to the activity of the other two strains did not decrease after maximum enzyme activity was reached. There were positive correlations between chitin content, protein content and chitin synthase activity during the active growth phase of the fungi indicating that they could be confidently used to determine in vitro growth phase and biomass concentration. PMID- 1855653 TI - Hyphen or slash? Coming of age. PMID- 1855654 TI - Problematic behavior of drug-dependent patients in the general hospital. A clinical and administrative approach to management. AB - Drug-dependent patients in general hospitals behave in ways that are difficult for medical and surgical staff to manage. Common problems include drug-seeking, states of intoxication and withdrawal, poor compliance, and behavior that is disruptive or dangerous to others. The authors describe an approach to these problematic behaviors based upon early recognition, a clinical perspective, and administrative action. Institutional initiatives are needed to overcome the practical and conceptual obstacles to effective management of these patients. PMID- 1855655 TI - Mental disorders in the primary care setting. Research priorities for the 1990s. AB - New research directions should be pursued during the coming years if mental illness is to be properly managed in primary medical care practice. Among needed studies are those pertaining to the validity of diagnostic classifications specific to psychiatric morbidity in ambulatory medical settings; the nature of clinical decision-making by primary care physicians; how diagnostic formulations influence treatment choices; and the effectiveness of treatments transferred from the specialist to generalist settings. PMID- 1855656 TI - Psychiatric aspects of head and neck surgery. Part I: New surgical techniques and psychiatric consequences. AB - Individuals who undergo head and neck surgery experience extreme stressors that go beyond those which occur with the usual surgical patient. This paper will review the literature and discuss the psychiatric consequences of otolaryngeal surgery. In addition, new head and neck surgical techniques, which offer special challenges to the patient as well as to the psychiatric consultant, will be examined. Tracheostomy, which occurs as a result of head and neck surgery, is of particular importance with regard to postoperative adaptation and is a significant complication that must be reckoned with. PMID- 1855657 TI - The misdiagnosis of conversion disorder in a psychiatric emergency service. AB - During a 1-year period, 8400 patient presentations to a psychiatric emergency service were screened for the conversion symptom of extremity paresis/paralysis. Of 4220 unduplicated presentations, three patients had this complaint. These cases were reviewed and followed up. All had received a DSM-III diagnosis of conversion disorder, but in each case the patient's conversion symptom was attributed to organic disease. This had medicolegal consequences in one case and threatened legal consequences in the others. Although the frequency of this alleged conversion symptom was 0.07%, in reality it was 0.0%. Guidelines for the management of the alleged conversion symptom of paresis/paralysis are discussed. PMID- 1855658 TI - Consultation-liaison psychiatry. Does it help to get organized? The European Consultation-Liaison Workgroup. AB - Since 1987 consultation-liaison (C-L) psychiatrists in Europe have decided to develop a closer collaboration to stimulate the development of the C-L field. A first result of this collaboration is a companion paper on the history and current state of C-L psychiatry in Europe. This paper describes the arguments for the development of the European Consultation-Liaison Workgroup for General Hospital Psychiatry and Psychosomatics (ECLW), and the results of the first 3 years of collaboration. PMID- 1855659 TI - [Localization of camphor degradative plasmids on the chromosome of Pseudomonas putida strains PaW]. AB - Camphor degradative plasmids (CAM, pRK1) are preferentially situated on chromosomes of Pseudomonas putida strains PaW. After having been transferred into Cam+ strains, the TOL plasmid pWWO dissociates into the cryptic plasmid pWWO-8 and chromosome-borne transposon Tn4651. The opposite situation, i.e. reconstruction of the TOL plasmid pWWO from the cryptic plasmid pWWO-8 and chromosome-borne catabolic operons of the pWWO plasmid has been described. Cam- derivatives of the CAM plasmid were obtained in vivo which contain the TOL plasmid transposons Tn4651 or Tn4652 as obligatory structural elements. These plasmids as well as pWWO-8 determine conjugational mobilization of chromosome located cam operons followed by their integration into the chromosome of recipient. PMID- 1855660 TI - [Incomplete translocations induced in mature sperm of Drosophila]. AB - Frequencies of incomplete translocations in subcentromeric heterochromatin induced by gamma-rays in mature sperm were estimated in the "two right acrocentrics and left compound" system of Drosophila chromosome 2. The value obtained at 3000R was (2.5-2.9) X 10(-3). Apart from incomplete translocations leading to formation of new metacentrics, acrocentrics were also formed. It is suggested that they appear via reunion of fragments after replication of paternal chromosomes. Incomplete translocation were shown to be formed as a result of loss of centric heterochromatin fragment of acrocentric and acentric arm of the compound, as opposed to formation, due to loss of acentric heterochromatin fragment of acrocentric and centric fragment of the compound. Analysis of the dose-effect curve for half-translocations show that the latter are two hit events. PMID- 1855661 TI - [Comparison of frequencies of complete and incomplete translocations induced in mature sperm of Drosophila]. AB - A frequency of induction of translocations taking place in mature sperm of Drosophila between heterochromatic portions of the 2L compound and 2R acrocentric was estimated to be 9.62 X 10(-3). This value is being compared with the previously estimated frequency of incomplete translocations in this system which is (2.5-2.9) X 10(-3). The ratio of frequencies of complete and incomplete translocations obtained was intermediate between the Panshin data, on the one hand, and those of Muller and Hershkowitz, on the other. The reasons for these discrepancies are under discussion. Based on the value obtained for this ratio, the probability of reunion of chromosome break (q) is calculated to be 0.79. PMID- 1855662 TI - [Enzyme proteins of different classes of northern red-backed and large-toothed red-backed voles]. AB - Electrophoretic characters of 9 enzyme systems from different tissue homogenates supposedly controlled by 17 loci are described. Polymorphism detected in loci for glutamate-oxalate transaminase, adenylate kinase, esterase D. glucosephosphate isomerase was thoroughly investigated. Methodic characteristics of enzyme electrophoresis and population-genetic characters of the species studied are under discussion. PMID- 1855663 TI - [Genetic characterization of hybrid Holstein-Friesian and Laisind cattle of Vietnam]. AB - The types of blood hemoglobin, transferrin and albumin as well as the types of alpha s1-casein, beta-casein and beta-lactoglobulin revealed by starch-gel electrophoresis were used in analysis of the results obtained in crossings of Holsteins-Frisian and Laisind races of cattle bred in Vietnam. The nature of alteration in frequencies of alleles and genotypes for these proteins was shown. The indices of homo- and heterozygosity, the level of polymorphism and the number of effective alleles were calculated. The status of genetic balance has been regarded in polymorphic systems under study. Alongside with this, a type of inheritance of quantitative characteristics, such as milking, fat and albumin percentage in milk, lactation duration, the weight of newborns and cows after first calving were traced on the background of changes in frequencies of blood and milk proteins in starting variants and their crossbreeds in 3 generations. PMID- 1855664 TI - [Karyotype evolution in the genus Ellobius (Microtinae, Rodentia)]. AB - Comparative analysis was undertaken of the pattern of G-dyed chromosome sets of three Ellobius species: E. tancrei, E. fuscocapillus, E. lutescens with respective diploid chromosome numbers 54, 36, 17. From the data obtained one can envisage probable evolutionary pathway of the Ellobius karyotype. Variability in chromosome numbers of this genus species was shown to be a result of both centromeric and centromeric-telomeric as well as telomeric translocations of originally acrocentric chromosomes. No combinations of acrocentric chromosomes of the E. tancrei Robertsonian fan were found in the karyotypes of E. fuscocapillus and E. lutescens, which points to independence of the evolutionary processes in the Ellobius genus taking different routes. The data are obtained to the effect that evolution of the genus Ellobius was accompanied by increase in the amount of C-heterochromatin. PMID- 1855665 TI - [Phenotypic variability and correlation between skinfold thickness and arterial pressure level]. AB - Contribution of genetic and environmental factors in phenotypic variability of blood pressure level and skinfold thickness, and phenotypic correlation between these characters was calculated on the basis of familial correlations. It was shown that genetic determinant explains considerable portion of blood pressure level and skinfold thickness variability. Among common environmental effects, the factors affecting one generation are important with regard to variability of these characters. Maternal effect is expressed in the variability of systolic and diastolic blood pressure. Correlation between blood pressure level and triceps skinfold thickness is determined by genetic factors, whereas that between blood pressure level and subscapular skinfold thickness is mediated by environmental factors. The results obtained may be applied in populational prevention of cardiovascular disease. PMID- 1855666 TI - [Moral considerations in the re-introduction of blood transfusion in the 19th century]. AB - The reintroduction of human blood transfusion in the 19th century repeatedly gave rise to discussions within the profession whether this dangerous therapeutic procedure might be justified or not. Those who used it protested that they did not act irresponsibly or without a valuable indication. They stressed the possibly life-saving effect of transfusion in desperate cases, especially in cholera victims and in obstetrical cases with extreme loss of blood. Their opponents, on the other hand, emphasized the high risk and the insufficient theoretical basis of the procedure. This historical discussion illustrates a dilemma that is of great importance in medical ethics up to the present day. PMID- 1855667 TI - [Criticism of the physician in the middle ages--examples and trends from the 6th to the 12th century]. AB - The author presents examples of a critical attitude towards medicine and physicians which may be observed, with changing tendencies, throughout the Middle Ages. First, medicine was despised as a mechanical art or suspected of paganism because of its literary sources. Later, the divine nature of disease and healing on the one hand and the uselessness of medicine on the other were stressed. Finally, the integration, at the universities, of medicine in the system of scholastic learning was criticized by more practically minded men. Similar criticism may be observed in the Islamic world. As valiant defenders of medicine, the author quotes the learned Isidore of Sevilla (d.636) and the famous Rhazes (b.865) as well as the anonymous author of the "Lorscher Arzneibuch" of the 8th century. PMID- 1855669 TI - Development of simulators in medical education. AB - The historical development of simulators is presented in respect to their application in medical training. Simulators allow, to some extent, practical training without any inconvenience for patients. The earliest simulators in the history of medicine were the obstetrical manikins introduced towards 1700 by father and son Gregoire of Paris and primarily intended for the instruction of lay people, i.e. midwives. Their further development is followed up to contemporary models of highly specialized use. Since 1960 simulators are more and more used for the training of doctors, nurses and laymen in resuscitation techniques. In combination with computers, high-fidelity simulators were created which, e.g., react to anaesthetics like real human beings. Conclusions about future developments and uses of simulators in medical education, in view of their history, are provided. PMID- 1855668 TI - [Medical museum--museum medicine]. AB - The author gives a short survey of the beginnings of the Museum of the History of Medicine at the University of Zurich, created by Gustav Adolf Wehrli, MD (1888 1949), and of its further development. He insists on the present-day interest of such a museum: the study of ancient tools of the art of healing may elucidate complex problems that still defy the profession, and the presentation of such objects in a wide cultural and historical context may lead the attentive visitor to a better understanding of modern medicine. PMID- 1855670 TI - [A show window for the public. The newly organized medical historical museum of the Zurich university]. AB - The author describes the long search for a suitable place for the museum as well as the five years of planning, reconstructing and arranging the new display of often unique objects. The idea is to present the history of medicine with a view to lead the visitor to a better understanding of medicine in general and thus to a rather confident attitude towards the medicine of to-day. PMID- 1855671 TI - Mitochondrial damage by active oxygen species in vitro. AB - Under in vitro conditions involving formation of active oxygen species, rat liver mitochondria were found to undergo swelling, peroxidative decomposition of lipids, and distinct disorganization of ultrastructure. Supplementation with free radical scavengers such as superoxide dismutase (SOD), methionine, histidine, and tryptophan accorded considerable protection to the organelle. A possible correlation between oxygen radicals, membrane integrity, and calcium functions is indicated. PMID- 1855672 TI - Therapeutic potential of vitamin E against myocardial ischemic-reperfusion injury. AB - Myocardial ischemia is a disease process characterized by reduced coronary flow such that the supply of nutritive blood to heart muscle (myocardium) is insufficient for normal myocardial aerobic metabolism. Prompt reestablishment of coronary flow by invasive and noninvasive clinical procedures is the most direct and effective means of limiting myocardial damage in ischemic heart disease patients, although reperfusion carries with it an injury component which may reflect, at least to some degree, the toxic effects of partially reduced oxygen species and their participation in degenerative cellular processes such as membrane lipid peroxidation. Vitamin E, a lipophilic, chain-breaking antioxidant, is a prominent membrane constituent in heart muscle, where it modulates/regulates various aspects of heart muscle-cell metabolism and function. Vitamin E's beneficial effects against experimentally induced oxidative damage to the heart, along with inverse epidemiological correlations between plasma vitamin E level and either anginal pain or mortality due to ischemic heart disease, suggest that vitamin E might have protective and therapeutic roles against myocardial ischemic reperfusion injury. Laboratory investigations aimed at addressing this possibility have demonstrated that vitamin E supplementation protects isolated hearts against ischemic-reperfusion injury, and relatively more inconsistent and limited data document cardioprotective effects of vitamin E in some animal models of myocardial ischemia-reperfusion, especially when administered prior to the ischemic period. Clinical attempts to establish whether vitamin E has therapeutic benefit in ischemic heart disease patients remain inconclusive, having relied upon a variety of nonuniformly controlled protocols and a single, rather subjective endpoint (anginal pain). Consequently, although laboratory data constitute a conceptual context for and indirect support of the idea that vitamin E could be a cardioprotectant against ischemic-reperfusion injury, compelling clinical evidence regarding vitamin E's therapeutic potential in the ischemic heart-disease patient is lacking. Elective coronary revascularization would appear to provide an attractive clinical setting for evaluating the therapeutic efficacy of vitamin E in the context of cardiac ischemia-reperfusion. Further biochemical work would still be required to define how vitamin E exerts any cardioprotective effect observed in these patients. PMID- 1855674 TI - Protein glycation and oxidative stress in diabetes mellitus and ageing. AB - Hyperglycemia is increasingly regarded as the cause of the diabetic complications, in particular via the ability of glucose to glycate proteins and generate Maillard browning products which cross-link proteins and render them brown and fluorescent in vitro. Similar changes occur in vivo to long-lived proteins in diabetes mellitus as well as in ageing. The evidence supporting this route of glucose toxicity is discussed in the context of the ability of glucose to oxidize in vitro (catalyzed by trace amounts of transition metal) generating hydrogen peroxide, highly reactive oxidants, and protein-reactive ketoaldehyde compounds. It is suggested that protein browning in vivo may not result from the reactions of glucose with protein but from the transition metal-catalyzed reactions of other small autoxidisable substrates, such as ascorbate, with protein. Overall, studies of glycation and protein browning suggest a critical role for oxidative processes perhaps involving decompartmentalized transition metals and a variety of low molecular weight reducing agents in diabetes mellitus and ageing. PMID- 1855673 TI - Oxidative status and oral contraceptive. Its relevance to platelet abnormalities and cardiovascular risk. AB - Oral contraceptive (OC) use is a risk for thrombogenic events. This paper reviews effects of OC on oxidative status, coagulation, and platelet activity. Complicating effects of cardiovascular risk factors such as smoking, diabetes, hyperpidemia, and hypertension, are discussed. From these data we conclude that: 1. OC use modifies slightly but significantly the oxidative status in women and in animals by decreasing in plasma and blood cells the antioxidant defenses (vitamins and enzymes). 2. The changes in the oxidative status are related to an increase in plasma lipid peroxides apparently responsible for the hyperaggregability and possibly the imbalance in clotting factors associated with the OC-induced prethrombotic state. 3. These effects of OC appear to be increased by a high intake of polyunsaturated fat and counteracted by supplements of vitamin E. 4. The risk factors acting synergistically with OC, have all been shown to increase platelet reactivity. In addition, smoking, diabetes, and, to some extent, dyslipidemia are associated with an increased level of lipid peroxides and concomitant changes in the antioxidant defenses that can be additive to those induced by OC. Thus, free radicals and lipid peroxidation could be the underlying mechanism in the predisposition to thrombosis induced by most risk factors in OC users. 5. Results of epidemiologic and experimental studies in this field will be concordant only when diet and natural antioxidants will be systematically taken into consideration. PMID- 1855675 TI - Improving the standards of endoscopy. PMID- 1855676 TI - Endoscopic injection sclerosis: effective treatment for bleeding peptic ulcer. AB - One hundred and nine patients presenting with severe haemorrhage from benign peptic ulcers were randomised to either endoscopic injection sclerotherapy using a combination of 1:100,000 adrenaline and 5% ethanolamine or to conservative treatment. Only high risk patients with active bleeding or endoscopic stigmata of recent haemorrhage and accessible ulcers were considered. The two groups were well matched for age, shock, haemoglobin concentration, endoscopic findings, and consumption of non-steroidal anti-inflammatory drugs. The group treated endoscopically had a significantly reduced rebleeding rate (12.5% v 47%, p less than 0.001). Rebleeding was successfully treated in some patients by injection sclerotherapy, other patients underwent urgent surgery. While there was a tendency towards a lower operation rate and lower transfusion requirements in the treated group, this failed to achieve statistical significance. The use of injection sclerotherapy in the conservatively treated group after rebleeding undoubtedly reduced the number of surgical operations. Endoscopic injection sclerotherapy is effective in the prevention of rebleeding in these patients. PMID- 1855677 TI - Relation of upper gastrointestinal bleeding to non-steroidal anti-inflammatory drugs and aspirin: a case-control study. AB - We conducted a case-control study in five general hospitals in the region of Antwerp, studying 161 patients (102 men, 59 women) and hospital control subjects matched for age and sex to explore the relation between drug use and upper gastrointestinal bleeding from 'erosive lesions' (peptic oesophagitis, gastric erosions, gastric ulcer(s), or duodenal ulcer(s]. There was a highly significant difference between cases and control subjects in the use of non-steroidal anti inflammatory drugs (NSAIDs, excluding aspirin) (odds ratio 7.4, p less than 0.001; 95% confidence interval odds ratio 3.7 to 14.7). There also was a significant difference in the use of aspirin (odds ratio 2.2, p = 0.025; 95% CI odds ratio 1.3 to 4.0) and a highly significant difference regarding the presence of antecedents of peptic ulcer disease (odds ratio 5.5, p less than 0.001; 95% CI odds ratio 3.2 to 9.6). There was no significant difference in the use of other drugs, paracetamol and corticosteroids in particular, nor in the use of alcohol or tobacco. The patient group using NSAIDs was older, had more women, and had a higher mortality than the group not using NSAIDs. Among patients with bleeding gastric or duodenal ulcer(s), NSAID users were not more or less likely to have had symptoms of peptic ulcer disease, and had no higher frequency of multiple gastric or duodenal ulcers. The attributable risk for NSAID use was 0.30 (95% CI 0.23 to 0.37) and for aspirin use 0.14 (95% CI 0.08 to 0.20). PMID- 1855678 TI - Enhanced gastric mucosal haemostasis after upper gastrointestinal haemorrhage. AB - An endoscopic technique for the measurement of gastric mucosal bleeding time has been developed to study gastric haemostasis in patients with acute upper gastrointestinal haemorrhage. The relation of gastric mucosal bleeding time to skin bleeding time and nonsterodial anti-inflammatory drug usage was examined in 61 control patients and in 47 patients presenting with bleeding peptic ulcers or erosions. Gastric mucosal bleeding time was shorter in patients with haemorrhage (median 2 minutes, range 0-5 minutes) than in the control group (median 4 minutes, range 2-8 minutes) (p less than 0.001). Skin bleeding times were similar in the two groups (medians 4 minutes in patients with haemorrhage and 4.5 minutes in controls). In 21 patients with haemorrhage who were taking non-steroidal anti inflammatory drugs, the median gastric mucosal bleeding time (2.5 minutes, range 1.0-5.0 minutes) was similar to that in 26 patients with haemorrhage not associated with these drugs (2.0 minutes, range 0.0-5.0 minutes). These results show that gastric mucosal haemostasis is accelerated in response to haemorrhage in the upper gastrointestinal tract, even in patients taking nonsteroidal anti inflammatory drugs. This enhanced gastric haemostasis probably reflects a local protective response to minimise blood loss from the bleeding lesion. PMID- 1855679 TI - Cancer occurrence in a cohort of patients surgically treated for peptic ulcer. AB - A cohort of 4107 patients treated surgically for peptic ulcer between 1955 and 1960 was followed up to determine the incidence of cancer by record linkage to the Danish Cancer Registry. A total of 930 cases of cancer were observed during 76,634 person-years. Relative risks of cancer were computed by comparison with the recorded cancer incidence in the Danish population. During the first five years after surgery the relative risk of gastric cancer was slightly increased (RR = 1.43), but 5-15 years after the operation the risk was lower than expected (RR = 0.55). Thereafter, the relative risk of gastric cancer increased steadily and increased more than twofold after 25 years. Lung cancer occurred more frequently in the cohort members than expected (RR = 1.66), but the relative risk was independent of time since surgery. Malignancies other than gastric cancer and cancers related to tobacco smoking were close to the expected numbers. The results do not support the findings of a recent British study of similar size in which increased risks were reported for cancer at other sites. PMID- 1855680 TI - Endoscopic fine needle aspiration cytology in the diagnosis of gastro-oesophageal and colorectal malignancies. AB - In a prospective study we compared the diagnostic accuracy of endoscopic fine needle aspiration cytology with that of brush cytology and forceps biopsy in relation to gross tumour pattern and site in 265 confirmed consecutive cases of malignancy of the oesophagus, stomach, colon, and rectum. Aspiration cytology gave the highest diagnostic accuracy (94%), which was significantly better than that of brush cytology (84.9%) and biopsy (87.2%) (p less than 0.005). The difference was mainly related to tumour pattern. When compared to brush cytology and biopsy aspiration cytology was significantly better in submucosal tumours (92.9% v 7.1% and 14.3%, p less than 0.001); in infiltrative malignancies (95.8% v 90.1% and 78.9%, p less than 0.01), and in ulceronecrotic malignancies (90.9% v 36.4% and 45.4%, p less than 0.05). In polypoid malignancies there was a significant trend (p less than 0.05) in favour of forceps biopsy, with a diagnostic yield of 100% compared with 95% for aspiration cytology and 93.3% for brush cytology. The accuracy of the different techniques was not significantly related to the site of the tumour. The cumulative accuracy of aspiration cytology and biopsy was significantly better than that of biopsy and brush cytology (98.5% v 90.9%, p less than 0.005). Aspiration cytology was diagnostic in 21 of 24 lesions that were negative with both brush cytology and biopsy. There were no false positive cytology or histology results. We conclude that aspiration cytology is a simple, safe, and reliable technique with a high diagnostic yield and is of particular value in submucosal, infiltrative, and ulceronecrotic tumours. PMID- 1855681 TI - Impaired intestinal barrier function measured by differently sized polyethylene glycols in patients with chronic renal failure. AB - The intestinal mucosa plays a fundamental role as the site for absorption of nutrients, and as an important barrier from potentially harmful agents in the intestinal lumen. Little is known of the permeability properties of the intestinal mucosa in uraemic patients. The intestinal permeability to differently sized polyethylene glycols (PEGs; range 326-1254 daltons) was studied in nine patients with chronic renal failure (24 hour endogeneous creatinine clearance 5 24 ml/minute). The maximum 24 hour urinary recovery of PEGs was decreased in the uraemic patients but relatively more of the larger than the smaller PEGs were found in these patients. The results suggest a reduced urinary recovery of PEGs caused by renal dysfunction but also a relatively increased intestinal permeability to larger PEGs in the uraemic patients. PMID- 1855682 TI - Small bowel tumours: yield of enteroscopy. AB - A total of 258 patients with obscure gastrointestinal bleeding were referred for small bowel enteroscopy, a procedure which allows endoscopic evaluation of most of the small intestine. A small bowel tumour was found in 5% of patients. In 50% of patients no diagnosis could be made, but when the cause of obscure bleeding was discovered small bowel tumours were the single most common lesion in patients younger than 50 years. Small bowel tumours causing gastrointestinal bleeding may remain undetected despite extensive diagnostic evaluation. We conclude that small bowel tumours are the most common cause of obscure gastrointestinal bleeding in patients less than 50 years of age. Small bowel enteroscopy is diagnostic of small bowel tumours even when all previous diagnostic studies, including enteroclysis and angiography, are negative. PMID- 1855684 TI - Malignant colorectal polyps: venous invasion and successful treatment by endoscopic polypectomy. AB - We reviewed the pathology of 81 malignant colorectal polyps in 80 patients treated by endoscopic polypectomy and assessed the importance of carcinomatous invasion of veins in the stalk (submucosa). All the patients were followed up for at least five years. Venous invasion was present in 30 of the polyps (37%). The histological features of lymphatic invasion were considered too subjective to be of value. Most of the tumours were well or moderately differentiated adenocarcinomas, one was poorly differentiated, and one was a signet ring cell carcinoma. Seventy one patients were treated by polypectomy alone, and 58 of these were alive and well five years later, with no evidence of recurrence. Nine died of unrelated causes within five years, but four died of carcinomatosis: one with recurrent tumour, one with a possible metachronous caecal cancer, and in two patients there was late development of malignancy of uncertain nature. The remaining nine patients underwent surgical resection after initial endoscopic polypectomy because of incompleteness of excision, poor differentiation of the tumour, or a decision by the surgeon. Tumour was not present in the resection specimens apart from a single lymph node deposit in the patient with signet ring cell carcinoma. These nine patients were alive and well without evidence of recurrence five years later. The results reemphasize the necessity of good cooperation between endoscopist and pathologist, meticulous laboratory technique, strict histopathological criteria including examination of resection margins and degree of differentiation of the tumour, and regular endoscopic follow up. Endoscopic polypectomy of pedunculated and sessile malignant polyps is adequate treatment if the lesion can be removed in one piece, the tumour is well or moderately differentiated, and local excision is judged complete by endoscopic and histological criteria. Patients with histologically incompletely excised polyps, containing well or moderately differentiated carcinoma, can be safely managed by conservative treatment provided the endoscopist is certain there is no residual tumour. Venous invasion by tumour is a common finding in malignant colorectal polyps and seems to have no prognostic importance. PMID- 1855683 TI - Metabolism of dietary sulphate: absorption and excretion in humans. AB - Dietary sulphate may affect colonic pathophysiology because sulphate availability determines in part the activity of sulphate reducing bacteria in the bowel. The main product of sulphate reducing bacterial oxidative metabolism, hydrogen sulphide, is potentially toxic. Although it is generally believed that the sulphate ion is poorly absorbed, there are no available data on how much sulphate reaches the colon nor on the relative contributions from diet and endogenous sources. To resolve these questions, balance studies were performed on six healthy ileostomists and three normal subjects chosen because they did not have detectable sulphate reducing bacteria in their faeces. The subjects were fed diets which varied in sulphate content from 1.6-16.6 mmol/day. Sulphate was measured in diets, faeces (ileal effluent in ileostomists), and urine by anion exchange chromatography with conductivity detection. Overall there was net absorption of dietary sulphate, with the absorptive capacity of the gastrointestinal tract plateauing at 5 mmol/day in the ileostomists and exceeding 16 mmol/day in the normal subjects. Endogenous secretion of sulphate in the upper gastrointestinal tract was from 0.96-2.6 mmol/day. The dietary contribution to the colonic sulphate pool ranged up to 9 mmol/day, there being linear identity between diet and upper gastrointestinal losses for intakes above 7 mmol/day. Faecal losses of sulphate were trivial (less than 0.5 mmol/day) in the normal subjects at all doses. It is concluded that diet and intestinal absorption are the principal factors affecting the amounts of sulphate reaching the colon. Endogenous secretion of sulphate by colonic mucosa may also be important in determining amounts of sulphate in the colon. PMID- 1855685 TI - More accurate diagnosis of irritable bowel syndrome by the use of 'non-colonic' symptomatology. AB - The criteria now used in an attempt to distinguish irritable bowel syndrome from organic gastrointestinal disease rely almost entirely on symptoms of colonic origin. 'Non-colonic' symptoms, however, arising either from elsewhere in the gut or of a more general nature, are common in irritable bowel syndrome and may have even better diagnostic potential. The prevalence of these non-colonic features was assessed in 107 patients with the irritable bowel syndrome and 295 subjects with other gut disorders. Gastrointestinal type non-colonic symptoms are useful in differentiating irritable bowel syndrome from inflammatory bowel disease but, with the exception of early satiety, are not helpful when there is gastro oesophageal or biliary disease. More general 'non-colonic' features, such as lethargy and backache, are much commoner in irritable bowel syndrome than in all the organic gastrointestinal diseases studied and have good discriminant function. Multiple logistic regression analysis identified certain features that had a particularly significant independent risk for irritable bowel syndrome. Those were lethargy (relative risk 6.7), incomplete evacuation (RR 5.2), age under 40 (RR 2.1), backache (RR 2.0), early satiety (RR 1.8), and frequency of micturition (RR 1.8). These relative risks can be multiplied together to give an overall risk when more than one of these features is present in a patient. Until a diagnostic test is available more confident diagnosis of irritable bowel syndrome can be achieved by identifying symptoms that have good discriminant function. The results of this study indicate that the non-colonic features of irritable bowel syndrome may be especially valuable in this respect. PMID- 1855686 TI - Prospective hospital based study on persistent diarrhoea. AB - A total of 383 children aged less than 5 years suffering from acute watery diarrhoea or dysentery were studied in hospital to determine the rate of persistent diarrhoea. Altogether 335 (87.5%) recovered within 13 days. Only in 48 (12.5%) did the diarrhoea continue for 14 days or more, and they were considered as having persistent diarrhoea. Children aged between 7 and 18 months had a significantly increased incidence of persistent diarrhoea. Children suffering from grade II-IV malnutrition constituted the majority (70.8%) of those with persistent diarrhoea. Higher rates of isolation of Shigella flexneri, Shigella dysenteriae 1, and Salmonella typhimurium were observed among patients with persistent diarrhoea than in those with diarrhoea of shorter duration. No positive correlations were observed between the clinical severity of disease at hospital admission and measles. Breast fed babies were not prone to persistent diarrhoea. PMID- 1855687 TI - Clostridium difficile toxin A induces a specific antisecretory factor which protects against intestinal mucosal damage. AB - Peroral challenge with toxin A from Clostridium difficile induced the formation of antisecretory factor in rats. The animals were given 100 micrograms of the toxin, which was followed by a pronounced diarrhoea and by the appearance of antisecretory factor in the pituitary gland. In electrofocusing, the induced antisecretory factor separated in two peaks (pI 5.4 and 5.0); both fractions showed a lectin-like binding to agarose. The pI 5.4 fraction inhibited cholera toxin as well as toxin A induced fluid secretion, while pI 5.0 inhibited toxin A induced secretion only. Immunohistochemistry showed that an antisecretory factor of pI 5.0 protected the mucosa from the cytotoxic effect of toxin A, but did not affect the binding of toxin A to the intestinal epithelium. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the pI 5.0 protein showed two major fractions to be present, one of molecular weight 60 kDa, the other of 30 kDa, the latter probably being a degradation product of the former. PMID- 1855688 TI - Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet. AB - This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal. PMID- 1855690 TI - Glutathione S-transferase in humans in health and disease. PMID- 1855691 TI - Combination of cimetidine and alginic acid: an improvement in the treatment of oesophageal reflux disease. Cooperative Oesophageal Group. AB - A new chewable tablet containing cimetidine 200 mg and alginic acid 500 mg, at a dosage of one tablet four times daily, was compared in a 12 week randomised study with the standard dosage of cimetidine (400 mg four times daily) in the management of oesophageal reflux disease. The dose of cimetidine continued unchanged throughout the study but the dose of the combination drugs could be increased after six weeks to two tablets four times a day if response was unsatisfactory. A total of 312 patients had data suitable for analysis. Sixty three per cent of those on the combination tablet completed the study without increasing their dose - that is taking cimetidine equivalent to half the standard dosage used in the control group. The improvement in heartburn symptoms was significantly greater in the combination group than in the group taking full dose cimetidine. There were no significant differences between the treatment groups in healing and improvement of the appearances of oesophagitis after 12 weeks, and healing rates were as expected from previous studies. The addition of alginic acid to cimetidine in this fixed combination tablet is an improvement in symptomatic treatment of oesophageal reflux disease. PMID- 1855692 TI - Recommendations for standards of sedation and patient monitoring during gastrointestinal endoscopy. AB - (1) Safety and monitoring should be part of a quality assurance programme for endoscopy units. (2) Resuscitation equipment and drugs must be available in the endoscopy and recovery areas. (3) Staff of all grades and disciplines should be familiar with resuscitation methods and undergo periodic retraining. (4) Equipment and drugs necessary for the maintenance of airway, breathing, and circulation should be present in the endoscopy unit and recovery area (if outside the unit) and checked regularly. (5) A qualified nurse, trained in endoscopic techniques and adequately trained in resuscitation techniques, should monitor the patient's condition during procedures. (6) Before endoscopy, adverse risk factors should be identified. This may be aided by the use of a check list. (7) The dosage of all drugs should be kept to the minimum necessary. There is evidence that benzodiazepine/opioid mixtures are hazardous. (8) Specific antagonists for benzodiazepines and opioids exist and should be available in the event of emergency. (9) A cannula should be placed in a vein during endoscopy on 'at risk' patients. (10) Oxygen enriched air should be given to 'at risk' patients undergoing endoscopic procedures. (11) The endoscopist should ensure the well being and clinical observation of the patient undergoing endoscopy in conjunction with another individual. This individual should be a qualified nurse trained in endoscopic techniques or another medically qualified practitioner. (12) Monitoring techniques such as pulse oximetry are recommended. (13) Clinical monitoring of the patient must be continued into the recovery area. (14) Records of management and outcome should be collected and will provide data for appropriate audit. PMID- 1855693 TI - Primary malignant melanoma of the oesophagus: case report and review of surgical pathology. AB - Primary malignant melanoma of the oesophagus is both a rare presentation for melanoma and a cause of oesophageal neoplasm. It accounts for less than 0.1% of all primary oesophageal neoplasms. It was first recognised as a primary tumour by de la Pava et al who showed the presence of melanocytes within oesophageal mucosa. This case report includes a review of the surgical pathology. Even though it is a rare lesion it must be considered as a cause of polypoidal oesophageal lesions as both its diagnosis and treatment can present problems. It is usually fatal within one year. PMID- 1855694 TI - Pressure-volume characteristics of the rectum. PMID- 1855689 TI - Biology of pancreatic cancer. AB - Pancreatic cancer is the fifth leading cause of death from malignant disease in Western society. Apart from the fortunate few patients who present with a resectable small pancreatic adenocarcinoma, conventional treatment offers no hope of cure and has little palliative value. Over the past two decades major steps have been made in our understanding of the biology of pancreatic growth and neoplasia. This review sets out to explore these advances, firstly in the regulation of normal pancreatic growth, and secondly the mechanism which may be involved in malignant change of the exocrine pancreas. From an understanding of this new biology, new treatment strategies may be possible for patients with pancreatic cancer. PMID- 1855696 TI - Sedation for upper gastrointestinal endoscopy. PMID- 1855695 TI - Why do patients with ulcerative colitis relapse? PMID- 1855697 TI - Ultrastructural demonstration of histamine in human enterochromaffin like cell granules. PMID- 1855698 TI - [Development of an electronic calculator for gestational age in prenatal care]. AB - The development of a portable electronic gestation calculator enables the obstetrician for the first time to recall all relevant data for his daily routine work from an electronic memory. This is useful not only for the calculation of the duration of pregnancies or the determination of delivery data, but also includes all relevant information from ultrasound biometry of the fetus. This paper presents the experience with this new electronic device, 'Babycomp', and comments on its design, technical features, functions and performance. The device has been thoroughly tested especially with respect to its suitability for practical purposes. Compared with the widely used disk for pregnancy calculations, the 'Babycomp' has a wide range of advantages for all users working in the field of obstetrics and reproductive medicine. PMID- 1855699 TI - [Pearl index of the new Sof-T spiral in relation to ultrasound follow-up]. AB - 463 patients (109 nulliparae, 354 uni- and multiparae) were fitted with a new intrauterine device (IUD), Sof-T, and observed during 6,624 cycles. Two independent centres participated in the study. The T of Sof-T is made of flexible polyethylene, the two occlusion bodies, of medically approved silastic. If the Sof-T is correctly placed, they lie in the uterine horns. A copper wire of a total surface of 360 mm2 is winded around the vertical branch. The echogenicity of the occlusion bodies facilitates their visualization by ultrasound, thus improving the safety of the new Sof-T. The softness and the adaptability of these occlusion bodies to the cavity of the uterus decreased trauma, and thus hemorrhage and pain, compared to 16 other studies on IUDs. The small number of salpingitis recorded in our study of the Sof-T may be attributed to the fact that the pathogens transported and transmitted by sperm could probably not penetrate into the uterine tubes because they were stopped by the occlusion bodies. PMID- 1855700 TI - [Is there a correlation in the frequent association of neuroblastoma-fetal malformations?]. AB - We discuss the pathogenicity of the association between neuroblastoma and fetal malformations. It appears to us that the role of certain oncogenes could possibly go further than only activate tumors and play a role in the initiation of the process of fetal malformations. PMID- 1855701 TI - [Tasks in urogynecologic ambulatory care]. PMID- 1855702 TI - [Recurrent stress incontinence]. PMID- 1855703 TI - The Keller resection arthroplasty: a 13-year experience. AB - The clinical results following Keller resection arthroplasty were reviewed in 54 feet with a 2- to 10-year follow-up. Patients were evaluated by radiographs, physical examination, and questionnaire. The primary indication for surgery was painful hallux valgus with associated degenerative changes of the first metatarsophalangeal joint. Additionally, rheumatoid arthritis was the underlying diagnosis in four feet. Seventy-five percent of all patients had complete relief of their symptoms. There was significant (P less than .01) improvement in both the metatarsophalangeal and intermetatarsal angles, but a decreased range of motion in the first metatarsophalangeal joint, with a complete lack of plantarflexion in 67%. Application of the Bonney and MacNab2 grading system yielded a 72% rate of good and excellent results. The subjective patient satisfaction rate was 87.5%. Patient satisfaction was most strongly associated with the use of a K-wire for postoperative fixation (P = .03), and a limited resection of the proximal phalanx (P = .03). We conclude that the Keller resection arthroplasty is a reasonable alternative for the treatment of hallux valgus in the presence of degenerative changes in the first metatarsophalangeal joint. PMID- 1855705 TI - Crescentic osteotomy for hallux valgus: a biomechanical study of variables affecting the final position of the first metatarsal. AB - The position of the first metatarsal following a crescentic osteotomy for hallux valgus is a function of the size of the saw cut and orientation of the osteotomy. This study reports the effect of these variables, recommended technique, and potential pitfalls when using the crescent osteotomy. Using molded polyurethane foam metatarsals and a precision drill press which controlled the saw cuts, the following variables were studied: (1) orientation of the saw cut to the metatarsal, (2) the saw size (diameter of the saw relative to the shaft width of the osteotomy site), and (3) the direction toward which the crescent faces (proximal/distal). Best correction can be obtained if the saw diameter is larger than the diameter of the osteotomy site (allowing a greater degree of correction before impingement), the saw tip is tilted slightly toward the sesamoids (which ensures that the metatarsal does not rotate medially with correction), and the saw is rotated laterally to cause slight declination of the toe. PMID- 1855704 TI - Treatment of bunionette deformity with longitudinal diaphyseal osteotomy with distal soft tissue repair. AB - Twenty patients (30 feet) with symptomatic bunionettes refractory to conservative care underwent longitudinal diaphyseal osteotomy, lateral condylectomy, and distal metatarsophalangeal realignment. At an average of 31 months followup, 93% (28 feet) noted good or excellent results. This technique was found to be useful and predictable in correcting the bunionette deformity. PMID- 1855706 TI - The stability of fixation of first metatarsal osteotomies. AB - Five different types of osteotomies for the correction of the hallux valgus deformity were performed on dried human first metatarsal bones. These included the step-cut Mitchell osteotomy, a distal transverse osteotomy, a distal biplanar osteotomy, the Chevron osteotomy, and a basilar osteotomy. Each type of procedure was then fixed using a variety of clinically appropriate techniques including single K-wires, crossed K-wires, a single A-0 cancellous screw, a single A-0 cortical screw, and three different types of sutures. Specimens were placed in a test jig and physiological loads applied with a Materials Testing Systems servohydraulic testing machine (Minneapolis, Minnesota). No difference in stability was observed between the various types of osteotomies, except for the Chevron osteotomy, which did possess greater inherent stability. Fixation by screws or multiple K-wires provided the most stable configuration when compared to other methods. The postoperative regimen following first metatarsal osteotomy should take into account the relative stability of fixation. Cast immobilization and a nonweight-bearing status may be preferable after procedures characterized by less mechanical stability. PMID- 1855707 TI - The use of open phenol blocks to the motor branches of the tibial nerve in adult acquired spasticity. AB - Spasticity of the posterior calf muscles often occurs following head injury or spinal cord injury. If left untreated, equinovarus contractures of the foot and ankle may occur in a relatively short time period. This paper retrospectively reviews nine patients with either closed head injury (six patients) or spinal cord injury (three patients) who underwent open phenol injections into the motor branches of the tibial nerve in 16 limbs. Spasticity was decreased in all patients. No significant equinus contractures had occurred at final follow-up. Five of the patients were subsequently able to ambulate. One patient had recurrence of spasticity requiring a second surgical procedure (split anterior tibial tendon transfer), and two patients had significant toe clawing at final follow-up. Open phenol injections to the motor branches of the tibial nerve safely and effectively prevent foot and ankle contractures following spinal cord injury or head injury. PMID- 1855708 TI - Tibio-talar stability in bimalleolar ankle fractures: a dynamic in vitro contact area study. AB - A dynamic weight-bearing model has been developed in a cadaveric ankle model to assess the contact areas of the talus in varying degrees of bimalleolar ankle fractures. A surgically created transverse fibula osteotomy with up to 6 mm of displacement did not cause a significant change in the contact area. Sectioning of the deltoid ligament, regardless of fibular displacement, created a 15% to 20% decrease in the contact area (P less than .001). This model represents a clinically relevant situation, as it examines motion of an unconstrained, axillary loaded ankle. Additional medial side disruption increases ankle instability by allowing anterior and lateral translation of the talus out of the mortise. Isolated lateral malleolar displacement does not appear to cause ankle instability. PMID- 1855709 TI - Glove perforation in foot surgery. AB - A total of 391 pairs of gloves were tested for punctures after 100 consecutive foot surgery operations to assess the rate, site, procedure, and maneuver during which glove puncture accidents took place. Evidence of perforation was found in 23% of the gloves used. The surgeons are significantly more at risk of glove perforation than the other members of the operating team. PMID- 1855710 TI - Traumatic boutonniere deformity as a cause of acute hammer toe: a case report. AB - Traumatic boutonniere deformity, well-described when occurring in the fingers, can occur in a lesser toe. The deformity mimics that of a hammer toe, but the onset is acute, and develops immediately after trauma. Open repair of the central slip rupture and recentralization of the displaced lateral bands of the extensor mechanism with temporary pinning of the toe can give an excellent result. PMID- 1855711 TI - Foot and ankle disorders resulting from Lyme disease. AB - Ten cases of Lyme disease involving the foot and ankle are reported. Onset of symptoms was months to years before diagnosis. A variety of clinical foot and ankle problems resulted. Careful case histories and serologic testing resulted in proper diagnosis and treatment. PMID- 1855712 TI - Step-cut osteotomy of the medial malleolus for exposure of the medial ankle joint space. PMID- 1855713 TI - Tibialis posterior: a review of anatomy and biomechanics in relation to support of the medial longitudinal arch. AB - The medial longitudinal arch is unique among homo sapiens. This specialization of the human foot is believed to be necessary to the habitual bipedal gait pattern. Mechanical integrity of the arch depends on static and dynamic anatomic factors. The posterior tibial tendon in particular is situated to provide dynamic support along the plantar aspect of the foot and arch. Evaluation of the phasic activity of the posterior tibial muscle appears to confirm this premise. Furthermore, changes in the longitudinal arch that occur when the posterior tibialis is deficient lend further evidence that it is important in maintenance of the normal arch. PMID- 1855714 TI - Longitudinal attrition of the peroneus brevis tendon in the fibular groove: an anatomic study. PMID- 1855715 TI - Microscopical study on estimation of time since death in skeletal remains. AB - For the purpose of estimating time since death in skeletal remains, postmortem changes in human compact bones were examined by microradiography and electron microscopy. The UV-fluorescence of the peripheral zone of compact bone was also examined by microscopic spectrophotometry. Microradiographic examination revealed no morphological changes in bones left in the open air for long periods, except one of 15 years since death. In bones left in the soil, vacuoles of 5-10 microns diameter, which contained a honeycomb-like structure formed by small vacuoles of 0.5-1 microns diameter, were found in the peripheral zone of the substantia compacta approximately 5 years since death, and in bones of 6 years or more, this change extended to the mid-zone. In bones left in the sea for 4-5 years, vacuoles of 5-10 microns diameter were observed in the outer peripheral zone of the substantia compacta. The relative intensity of UV-fluorescence in bones dwindled with time since death and the correlation coefficient was considerably high. PMID- 1855716 TI - The manner and cause of death in a forensic series of chronic alcoholics. AB - Chronic alcoholics account for an increasing number of the cases which are examined in forensic pathology. The manner and cause of death in 122 chronic alcoholics is described and compared with a previous investigation and to a group of non-alcoholics. The percentage of cases in which the manner of death is undetermined is twice as high as in the control group, whilst the percentage of suicide, surprisingly enough is only half that of the control group. The patho anatomic findings in the liver and the causes of death are discussed in detail. PMID- 1855717 TI - Interaction of butorphanol, with monoamine oxidase inhibitor, tranylcypromine. AB - This investigation examines the possibility of interaction between tranylcypromine and butorphanol in comparison to pethidine. The LD50 of pethidine and butorphanol were determined in mice pretreated with the non-selective monoamine oxidase (MAO) inhibitor, tranylcypromine orally for 8 days or with oral saline solution. Tranylcypromine decreased the LD50 of both pethidine and butorphanol by 78% and 41%, respectively. Anesthetized rabbits with halothane pretreated with tranylcypromine or saline were given pethidine (5 mg/kg i.v.) or butorphanol (0.5, 1 and 2 mg/kg i.v.). Pethidine produced a marked increase in blood pressure in rabbits pretreated with tranylcypromine and did not affect significantly the heart rate. Butorphanol did not affect either blood pressure or heart rate at doses of 0.5 or 1 mg/kg. However, the largest dose of butorphanol (2 mg/kg) produced hypotension and tachycardia in rabbits pretreated with tranylcypromine. Neither pethidine nor butorphanol affected the temperature of anesthetized rabbits pretreated with tranylcypromine or saline. PMID- 1855718 TI - A fatal case of oral ingestion of methanol. Distribution in postmortem tissues and fluids including pericardial fluid and vitreous humor. AB - A 41-year-old man ingested orally a large quantity of methanol and was found dead at home. The presence of methanol in body fluids and tissues was determined by head-space gas chromatography. The blood ethanol and acetone were negative. Tissue distribution of methanol showed that the kidney presented the highest content of methanol (5.13 g/kg) followed by liver (4.18 g/kg), vitreous humor (3.96 g/l), heart (3.45 g/kg), urine (3.43 g/l), pericardial fluid (3.29 g/l), blood (2.84 g/l) and finally stomach content (2.21 g/l). PMID- 1855719 TI - Analysis of methylbenactyzium bromide in human urine by thin-layer chromatography and pyrolysis gas chromatography. AB - A rapid and simple method of utilizing thin-layer chromatography (TLC) and pyrolysis gas chromatography (PyGC) for the identification and determination of methylbenactyzium bromide in human urine was studied in this report. Methylbenactyzium bromide was extracted from urine with ODS-cartridge (Sep-Pak C18), then spotted onto a silica gel 60 F254 TLC plate. After development, the separated spot of methylbenactyzium bromide was scraped and wrapped with a ferromagnetic foil without extraction by any organic solvents. The sample was applied into PyGC analysis. The optimum temperature for pyrolysis was 590 degrees C. The main degradation product of methylbenactyzium bromide was identified as diphenylmethane in this procedure by gas chromatography/mass spectrometry (GC/MS). A calibration graph prepared by absolute calibration method showed a good linearity over the concentration range of 1-75 micrograms/spot for methylbenactyzium bromide. The coefficient of variation obtained for eleven replicate analyses of the 3 micrograms/spot of standard methylbenactyzium bromide was 3.8%. The detection limit of this compound by this procedure was 0.1 micrograms/spot. PMID- 1855720 TI - Determination of ring- and N-substituted amphetamines as heptafluorobutyryl derivatives. AB - An improved derivatization method for analysing 12 ring- and N-substituted amphetamine-derivatives in body fluids or seized materials by gas chromatograph combined either with mass spectrometer, electron capture or nitrogen phosphorus detector is presented. Heptafluorobutyric anhydride is used as derivatization reagent. No heating or standing period is needed in this procedure. Most of the drugs considered were distinguishable from each other according to their retention times and all of them according to their EI mass spectra. The base peak or one of the most intense peaks in the mass spectra contained benzyl radical and the m/e values were different according to the substituent. PMID- 1855721 TI - A fatal case of parenteral paraquat poisoning. AB - The chief clinical and analytical aspects of the suicide of a 21-year-old male with psychiatric problems by parenteral administration of a 200 g/l aqueous solution of paraquat are described. Paraquat levels were determined in plasma, urine, kidney, liver and lung after autopsy. Tissue damage was studied by electron microscopy. The death ensued from pulmonary dysfunction 15 days after hospital admission. PMID- 1855722 TI - [Current status of linkage studies for gene localization in corneal dystrophies]. AB - Corneal dystrophies with primarily autosomal dominant inheritance have been clearly identified both histologically and histochemically. No information is available to date on the causal enzymatic protein defect of the individual forms of dystrophy. By using linkage analysis to study families with various corneal dystrophies, an attempt is being made with polymorphous markers to find an indirect indication for localization in a chromosome. Numerous factors which exclude linkage can be named for granular, lattice and Schnyder's corneal dystrophy. Our linkage analysis studies of a second family with Schnyder's dystrophy support our indications of linkage with the sites for adenylate kinase (AK1) and the AB0 blood groups on chromosome 9. PMID- 1855723 TI - [The limbus epithelium in vitro]. AB - The limbal basal epithelium contains the stem cells of the corneal epithelium. In order to study the regulation of these cells we developed models allowing their investigation. While an explant model based on n-heptanol debridement did not allow outgrowth of corneal epithelium onto culture dishes, a serum-free single cell clonal growth supported colony growth in limbal cells. MCDB 151 medium was supplemented with insulin, transferrin, selenium, hydrocortisone, phospho /ethanolamine and calcium. Single cells (5,000) were seeded onto 60 mm plastic dishes following combined digestion with dispase and trypsin/EDTA. Increasing CFE was noted until day 6, allowing increasing recruitment into proliferation. This model will serve as a tool for the further investigation of factors that might govern the regulation of the differentiation and proliferation of limbal epithelial cells. PMID- 1855725 TI - [Morphometric and qualitative changes in corneal endothelium in primary chronic open angle glaucoma]. AB - In a prospective study begun in March 1986, specular-microscopic endothelial cell photographs were taken in non-selected patients with primary, chronic, open-angle glaucoma who had not had intraocular surgery. Age-matched cataract eyes with normal intraocular pressure served as the control group. Standard specular microscopic examinations (Bio Optics LSM 2000 and Clinical Specular Microscope Camera) to evaluate the endothelial cell count, as well as the morphology and quality of the endothelium, revealed the following results. In 3204 normal eyes with normal intraocular pressure (10-20 mmHg), the cell count was observed to be age-dependent and to have an average value of 2293 +/- 394 cells/mm2; the cells generally had a regular arrangement. In 302 eyes with primary, chronic, open angle glaucoma with intraocular pressures between 19 and 32 mmHg, there was a significant (p less than 0.001) reduction, in cell count to 1582 +/- 248 cells/mm2. The cell picture was composed of clearly enlarged, but regularly arranged cells. A statistical evaluation (matched age groups, etc.) was carried out using the Mann-Wilcoxon rank test. PMID- 1855724 TI - [New osmotic additives to culture media for corneal preservation]. AB - We investigated the effect of hyaluronic acid, molecular weight 250,000 and 500,000 as an osmotic additive to corneal preservation media. Porcine corneal specimens were incubated in organ culture for 8 days, followed by endothelial cell count and ultrasonic pachymetry. The preservation medium MEM-Earle with 2% FCS contained either no additives, 6% dextrane, MW 500,000 2% chondroitin sulfate, 1% hyaluronic acid MW 250,000, or 1% hyaluronic acid, MW 500,000. Whereas corneal thickness was estimated to be about 4 mm in the group without osmotic additives, all other media kept the corneas thin between 700 and 760 microns. The endothelial cell counts after preservation were similar in all groups. As hyaluronic acid is a physiological substance of the eye, it may offer some advantages for corneal perservation. PMID- 1855726 TI - [Laser coagulation of the cornea with a holmium:YAG laser for correction of hyperopia]. AB - We present a new technique of hyperopic correction similar to radial thermokeratoplasty. A pulsed Ho: YAG laser was used that emitted radiation at 2.06 microns and was guided by a quartz fiber and a focusing hand piece. The penetration depth of this light in the cornea is about 400 microns. Eight or 16 concentric point coagulations result in steepening in the central cornea. This refractive change is inverse related to the distance to the cornea center, and it increases linearly with increasing laser pulse energy. In four blind eyes it was demonstrated that the parameters evaluated in cadaver eyes can be transferred to living eyes. Surprisingly, the refractive change so created of up to 5 dpt is stable within a period of 4 months. Immediately after surgery, concentric descemet folds can be detected, which gradually decrease within the period reported. PMID- 1855727 TI - [Glare and contrast with diffraction intraocular lenses]. AB - The quality of vision in patients with a diffractive multifocal intraocular lens was tested and compared to monofocal IOLs and to eyes with a beginning cataract. An automatic computer-assisted visual acuity and contrast-sensitivity test was used. Diffractive IOLs showed reduced contrast sensitivity in both dark contrast testing and bright contrast testing. The differences from monofocal IOLs were not statistically significant. Glare sensitivity was of the same degree in both IOL groups. In additional, visual acuity under reduced contrast conditions was measured at the Ocutrast with and without glare. There was no significant difference between IOL groups. The results obtained showed that contrast sensitivity with diffractive IOLs is not as good as with monofocal IOLs. In this study no significant differences were found. PMID- 1855728 TI - [Effect of cataract extraction on aqueous humor dynamics in patients with senile cataract. A prospective fluorophotometric study]. AB - The influence of posterior chamber lens implantation on the aqueous humor dynamics was investigated using anterior chamber fluorophotometry before and 9 weeks after cataract extraction and IOL implantation. Thirty-four patients finished the protocol. Patients with preexisting glaucoma or those having a history of ocular or systemic inflammation were excluded from the study, as were those taking topical or systemic drugs with potential influence on the aqueous humor dynamics. Nine weeks after IOL implantation a mean increase in aqueous humor flow was noted. This increase was highly significant (p less than 0.01, Student's paired t-test). There were no significant changes in aqueous humor dynamics in the unoperated fellow eyes which served as controls. The significant difference in aqueous humor flow 9 weeks after cataract extraction and IOL implantation indicates that the liberation of prostaglandins may cause an increase in the ease of outflow facility. PMID- 1855730 TI - [Subretinal lavage in fresh hemorrhage in macular degeneration]. AB - Three eyes with acute severe subretinal hemorrhages due to age-related macular degeneration were operated on by vitrectomy, retinotomy and subretinal lavage. It was possible to improve the visual acuity (VA) in case 1 from 20/500 preoperatively to 20/200 postoperatively; VA stayed the same for 16 months. In case 2 the VA was hand movements preoperatively, and postoperatively 20/200; after 18 months it was still 20/300. In case 3 VA was 20/400 preoperatively and 20/100 postoperatively; after 15 months it was 20/700. Even if this procedure cannot be recommended as routine, it can be considered in selected cases of subretinal hemorrhages no older than 1 week. PMID- 1855729 TI - [Prevention of cellular foreign body reactions to lens implants]. AB - A heparin-surface-modified PMMA IOL has recently been developed in order to give the IOL a hydrophilic surface and to reduce postoperative inflammatory reactions in the eye. It is known that severe inflammation accompanies a tremendous increase in leucocytes in IOLs. A foreign-body reaction is characterized by the formation of histiocytic giant cells. The topical administration of corticosteroids, or the surface passivation of IOLs, cannot prevent a foreign body reaction. Specular microscopy was used for in vivo investigation of cellular reaction in IOL surface of heparin-surface-modified lenses versus regular PMMA lenses. The double-masked and randomized study included 53 patients investigated 1 week and 1 month postoperatively. Small, round, and spindle-shaped cells were the cells most frequently observed after 1 week. These cells were identified in all cases. They were found in a higher density on the surface of the control lenses (43 cells/mm2) than on the heparin-surface-modified lenses (25 cells/mm2). Giant cells were found in two patients after 1 week; both of these patients belonged to the control group. Small, round, and spindle-shaped cells were also seen in all patients 1 month postoperatively. Again, they were found in a higher frequency on the control lenses (38 cells/mm2) than on the heparin-surface modified lenses (13 cells/mm2). Giant cells were found in 18 patients 1 month postoperatively. They were found exclusively on the control lenses; the difference was significant (p less than 0.0001). PMID- 1855731 TI - [Fluorescence angiography image of erythrocytes with the scanning laser ophthalmoscope]. AB - Erythrocytes bind fluorescein to their surface, but they do not take up the dye intracellularly during fluorescein angiography. The cells are therefore hypofluorescent compared to blood plasma. Due to the high velocity of red blood cells in retinal vessels, this phenomenon has not been observed during conventional angiography. Scanning laser ophthalmoscopy, however, allows imaging of the retina with a very high temporal resolution. The exposure time of the scanning laser beam for a single erythrocyte is in the range of only 100 ns. Therefore, scanning laser ophthalmoscopy permits imaging of fast-moving red blood cells in large retinal vessels. Pathologically reduced blood flow is clearly visible and can be measured with digital image analysis. The values found in three patients with vascular occlusions were between 0.1 and 1.8 mm/s. In cases with intact circulation, digital image analysis was not sufficient to measure red blood cell velocity. Even if a velocimeter that permits semiquantitative comparison between erythrocytes and moving black dots is used, superimposed on the angiogram, reliable results can only be obtained in cases with reduced red cell velocity. Nevertheless, for the clinician observation of erythrocyte flow during scanning laser angiography is a new and fascinating tool. PMID- 1855732 TI - [Aphakic retinal detachment in myopic eyes]. AB - The incidence of retinal detachment following cataract extraction was studied in a myopic population of 803 eyes, which were selected by a measurement of the axial length out of 3,184 cases consecutively operated on. The incidence of retinal detachment following intracapsular cataract extraction was 1.5%, which was very similar to that after extracapsular cataract extraction: 1.8%, in the lowest range of date published in the literature. The incidence of retinal detachment of the pseudophakic myopic eye (operated on with the extracapsular technique, combined with implantation of a posterior chamber lens, the PMMA optic disc, diameter 5.8 mm with a 10 degrees angulated haptic and modified prolene-C loops) was 1.1%, in which the cases of intraoperative posterior capsule rupture with vitreous loss were included. There was no correlation between the incidence of retinal detachment and axial length. All cases of retinal detachment appeared in eyes with an axial length of 24.2 to 27.0 mm. In 9 of 11 (75%), retinal detachments occurred during the first 18 months after cataract extraction. In our opinion extracapsular cataract extraction with implantation of a posterior chamber lens is the best method of providing postoperative retinal detachment of the cataractous myopic eye. The question of the incidence of retinal detachment following cataract removal by the extracapsular technique and secondary capsulotomy by the Nd-YAG laser is still interesting. PMID- 1855733 TI - The use of perfluorodecalin in diabetic vitrectomy. AB - Nine patients were operated on for severe proliferative diabetic retinopathy using a perfluorocarbon liquid, purified perfluorodecalin; 7 patients were operated on for traction-rhegmatogenous retinal detachment, 2 for severe fibrovascular proliferation complicated intraoperatively by iatrogenic holes with surrounding retinal detachment. The intraoperative use of perfluorodecalin allowed flattening of the retina and endophotocoagulation to be carried out easily. Perfluorodecalin was removed at the end of the procedure, and intraocular tamponade was provided by silicone oil in 5 eyes and by a long-acting gas in 4 eyes. Anatomic success was obtained in 8/9 cases with a minimum follow-up of six months; 4 eyes had improved vision, 2 had the same vision, and 3 had decreased vision. The main advantage of intraoperative use of perfluordecalin is to allow easy flattening of the retina and effective endophotocoagulation under optimal visual conditions. PMID- 1855734 TI - [Retinopathy of prematurity: why are girls more frequently affected?]. AB - In 226 prematures (birth weight less than or equal to 1500 g), who were examined prospectively between 1986 and 1988, retinopathy of prematurity occurred significantly more often in girls: 31.0% of the eyes of 134 girls and 22.3% of the eyes of 92 boys showed retinopathy of prematurity (p = 0.042). Different factors may influence the sex ratio of retinopathy of prematurity: (1) hormonal differences are already present shortly after birth; (2) there are different ventilation rates in girls and boys; (3) the mortality varies between girls and boys. The influence of mortality was demonstrated in the group of preterms examined: in this time period, 59 of 285 prematures died: 21 of 155 girls (13.5%) and 38 of 130 boys (29.2%). Significantly more boys than girls died (p = 0.001). For this reason the percentage of surviving girls at high risk of having retinopathy is high. The apparently greater prevalence in girls is the result. PMID- 1855735 TI - [Antibody titer to Toxoplasma gondii in uveitis of toxoplasmosis and other origin]. AB - The diagnostic value of toxoplasma serology in ocular toxoplasmosis is a controversial issue. Some authors feel that a positive titer indicates nothing more than that the patient had been exposed to Toxoplasma gondii at some stage. Even if in most cases the diagnosis is based on the morphological findings on the fundus, it might sometimes be useful to have an additional serologic evaluation. In a retrospective study we compared the level of antitoxoplasmosis antibodies (measured in a complement fixation test and an immunofluorescence test) in 75 patients with clinically proven ocular toxoplasmosis and 146 patients with uveitis of other origin. In our results we showed that the incidence of positive titers and antibody levels are significantly higher in patient with ocular toxoplasmosis than in other uveitis patient (chi 2-test, Mann-Whitney Willcoxon test, p = 0.05). There was no significant difference between antibody levels in patients with anterior uveitis, posterior uveitis or panuveitis of nontoxoplasmotic origin. No correlation between the antibody levels and amount of retinochorioidal fundus lesions could be found. Based on our results, we conclude that in cases where fundus findings are compatible with ocular toxoplasmosis and a complement fixation or immunefluorescence test is positive, specific antitoxoplasmotic therapy should be started. PMID- 1855736 TI - [Optimizing target volume assessment in irradiation of intraocular melanomas with ruthenium applicators]. AB - Radioactive applicators have been used for conservative therapy of melanomas in the vicinity of the nervus opticus and of melanomas of the ciliary body for a few years. The aim of optimal radiotherapy is to destroy all tumor cells and to protect the optic nerve and macula. Therefore, we calculated the dose distributions and isodoses for ruthenium applicators. Isodoses show underdosage or overdosage in the tumor area. We also present a calculation model with which it is possible to simulate selective shielding of activated parts of the applicator. PMID- 1855737 TI - [Bromocriptine in therapy of chronic recurrent anterior uveitis]. AB - In animal studies, bromocriptine (Pravidel) has demonstrated immunosuppression because of inhibition of prolactin. After publication of positive results in the treatment of uveitis in a few case reports and in an uncontrolled study we conducted a double-blind placebo-controlled study in 13 patients with chronic recurrent anterior uveitis who had experienced three or more recurrences during the previous year. Therapy was started gradually during the symptom-free interval and continued for 1 year with 2.5 mg twice daily. Two recurrences or relevant side effects led to discontinuation of the therapy. In the bromocriptine group, 2 of 7 patients had no recurrences during the study period. Two patients had to stop because of two recurrences but, in contrast to earlier recurrences, they responded to local corticosteriod treatment within a few days. The remaining 3 patients (1 with one recurrence, 2 without) had to stop because of the side effects (arterial hypotension, arthritic complaints). In 5 of 6 patients in the placebo group treatment was stopped because of recurrences and in 1 patients because she believed she was experiencing a side effect from bromocriptine (breast atrophy). In summary, bromocriptine seems to have a prophylactic effect on anterior uveitis. Side effects were frequent but mild compared to other immunosuppressives. In case of arterial hypotension, additional therapy could make this drug more tolerable. PMID- 1855738 TI - [Sub-epidermal calcinosis of the eyelid]. AB - We report on a 17-year-old male with an asymptomatic yellowish-grayish solitary tumor of the right medial upper lid margin. An excisional biopsy was performed and histopathologic examination revealed subepidermal calcinosis. The other eye showed a granulomatous chrorioretinits of unknown etiology. The relative rare occurrence of subepidermal calcification should be kept in mind when making a differential diagnosis of superficial lid tumors. In our histopathology laboratory this is the first diagnosis of subepidermal calcinosis among 1,400 comparable specimens from 1980 to 1990. A possible relationship between the subepidermal calcification and granulomatous chorioretinitis of the other eye is discussed. PMID- 1855739 TI - [Epiphora as the leading symptom of Urbach-Wiethe syndrome in a sibling pair]. AB - Urbach-Wiethe-Syndrom. syn. Hyalinosis cutis et mucosae is a rare, probably autosomal-recessively inherited disease. In the first weeks of life it begins with typical hoarness due to hyalin deposits in larynx and with increasing age leads to different changes in mucous membrane and later on in cutis. Etiology and pathogenesis are unknown. The treatment is only symptomatic. In our casuistic we present two sisters, who are constantly full of tears. Either show different stage of the typical representation of Hyalinosis cutis et mucosae. We demonstrate progression and penetrance of the disease and clinical alterations in eyes, skin and mucous membrane. PMID- 1855740 TI - [Effect of vasoconstrictor eyedrops on tear volume and tear secretion]. AB - Vasoconstrictive, alpha-sympathicomimetic eye drops are ophthalmic drugs that are extensively used. However, patients often complain of typical dry eye symptoms, especially after long-lasting application of such eye drops. In the present study, the effect of sympathicomimetic eye drops (oxymetazoline 0.026%) on the tear volume and tear flow of 16 healthy individuals was determined quantitatively by means of objective fluorophotometry. Both tear volume and tear flow were found to be significantly (p less than 0.001) decreased 3 h after instillation (tear volume: -52%; tear flow: -31%). Thus, alpha-sympathicomimetic eye drops containing oxymetazoline 0.026% lead to marked and protracted decrease in tear volume and tear flow. After frequent or long-lasting application, this fact may be responsible for severe dry eye conditions. PMID- 1855741 TI - [Microsurgical endonasal decompression of the optic nerve]. AB - A new endonasal microsurgical technique for decompression after traumatic optic neuropathy is presented. Compared to the external transethmoidal, the transfrontal or the pterional approach, the main benefit of this method is the superb stereoscopic vision of the medial aspect of the optic canal. The nerve is approached from a 60 degree to 90 degree angle and continuous suction irrigation allows for safe removal of the bony shell. This surgery is done via the endonasal route and therefore has fewer serious complications compared to intracranial, extradural or intradural approaches. Additional trauma due to retraction of the brain is avoided. The anterior ethmoidal cells and the nasofrontal duct remain untouched, avoiding late mucocele formation. PMID- 1855742 TI - [Comparative studies of twilight vision with the Mesoptometer I and II and the Nyktometer]. AB - In 44 persons (19 to 39 years old, visual acuity better than 1.0), mesopic vision and sensitivity to glare were measured under binocular conditions by means of Mesoptometer I and Mesoptometer II (Oculus) and Nyktometer (Rodenstock). No differences were found between the two mesoptometers, but the nyktometer provided significantly worse results (a difference of 2-3 numbers). Mesopic vision was improved by minus glasses in 20% of the cases (Mesoptometer I), in 39% (Mesoptometer II) or in 50% (Nyktometer). The last instrument evoked the greatest amount of accomodation ("instrument myopia"). The best instrument for testing mesopic vision and sensitivity to glare under natural conditions was Mesoptometer I. Equal results were obtained by Mesoptometer II. Because of the easy handling and reduced reliability of the results, the nyktometer can only be recommended for screening examinations. PMID- 1855743 TI - [Ocular motility disorders after retinal surgery]. AB - Motility disturbances after retinal detachment surgery are rare complications. This retrospective study examined 2427 cases from the University Eye Hospital in Munster (1/84-6/89). All cases underwent scleral buckling procedures for retinal detachment. Twelve patients developed persistent diplopia. The scleral buckle needed to be removed in all cases; however, additional strabismus surgery had to be done in 5 cases to restore binocular single vision. Evaluation of the 12 cases suggested that the complications were caused by hypertrophic scarring rather than by the buckles, suturing material or muscular decompensation. PMID- 1855744 TI - [Detection of retinal visual field defects by sectorial photic stimulation in scotopic luminance ERG]. AB - We developed an electroretinographic procedure to assess visual field defects due to dysfunction of the outer retinal layers. For this objective we determined the amplitude/intensity function of the scotopic b-wave to full field (100 degrees of visual angle), quadrant and hemifield stimulation in 14 healthy volunteers and in patients with visual field disturbances. To prevent stray light effects, we confined the test light illuminance to 10(1.3) of the extrapolated normal ERG threshold (about 10(4.2) the sensory dark threshold). Whereas patients with dysfunction of the proximal retinal layers or the optic nerve did not show any change when the corresponding visual field was stimulated, those suffering from disturbances of the distal retinal layers (e.g., amotio, chorioretinal diseases) showed a reduction in the amplitude/intensity function, which was related to the extension and the degree of the field losses. The method reveals visual field defects caused by disturbances in the outer retinal layers where one-fourth or more of the corresponding retinal quadrant exhibits a sensitivity loss of more than 15 dB. PMID- 1855745 TI - [VECP (pattern threshold, amplitude, latency) in different light levels. A comparison between healthy eyes, organic and functional amblyopia eyes]. AB - According to Bjerrum [5] and Ammann [2], light attenuation decreases visual acuity at different rates in normals, organic and functional amblyopes. In 27 normal subjects, 19 patients with central fixating squint amblyopia and 12 with organically poor vision, we determined the visually evoked cortical potential (VECP) threshold check size, P100 latency and P2 amplitude for reversing checkerboards of variable size at different levels of luminance. After light attenuation, we found a different rate of change for VECP threshold check size in normal subjects and patients with squint amblyopia, which lessened after the fovea was occluded. With suprathreshold checks, normal subjects and patients with squint amblyopia exhibited significantly smaller amplitude/latency changes after light attenuation than patients with organically poor vision. Only patients with squint amblyopia exhibiting a visual acuity of greater than 0.2 showed smaller VECP changes than normal subjects during light attenuation. According to these findings, the different rate of change in visual acuity after light attenuation in normal subjects and patients with squint amblyopia is locus specific [7] rather than luminance specific [12, 13]. We conclude that cortical disinhibition of the parafoveal retina [20] is responsible for the preservation of visual acuity in squint amblyopia during light attenuation. PMID- 1855747 TI - [Changes in therapy of ulcerative colitis and Crohn disease]. PMID- 1855746 TI - [Effect of hyaluronidase on ocular circulatory changes caused by retrobulbar anesthesia]. AB - Twenty patients had retrobulbar anesthesia with 5 ml mepivacaine (Scandicain) without or with addition of 150 units of hyaluronidase (Kinetin). Before and 15 min after injection, we determined--by means of oculo-oscillo-dynamography--the systolic retinal and ciliary perfusion pressures, the respective ocular blood pressures (intramural pressures) and the ocular pulsation volume (PVoc) as well as the intraocular pressure (Pio; hand-applanation tonometer). Without hyaluronidase, the ocular perfusion and blood pressures were lowered by 11.8 and 3.9 mmHg, respectively, and PVoc was reduced by 0,40 microliters, whereas Pio was increased by 7.9 mmHg With hyaluronidase, the ocular perfusion and blood pressures were decreased by averages of 12.7 and 6.8 mmHg, respectively, PVoc was reduced by 0.42 microliters, and Pio was increased by 6.0 mmHg. Within each group, all changes were significant. There were, however, no significant differences between the two groups, i.e., the "spreading factor" hyaluronidase does not influence the inhibitory effects of retrobulbar anesthesia on ocular circulation. PMID- 1855748 TI - [Prerequisites for therapy of inflammatory bowel diseases. Pathophysiology- symptomatology--diagnosis]. AB - The etiology of the idiopathic chronic inflammatory bowel diseases Crohn's disease and ulcerative colitis remains unclear. Differences in prognosis, medical and surgical treatment, and the nature of expected complications require not only a differential diagnosis vis-a-vis other disorders, but also the correct diagnosis of these two diseases. Symptomatology and clinical presentation can be mimicked both by infectious, ischemic and other chronic bowel diseases such as collagenous colitis, eosinophilic colitis, and Behcet's disease. This means that, in the absence of pathognomonic changes, the correct diagnosis can be established only on the basis of all the findings (laboratory, endoscopy, X-rays), and sometimes only on the basis of the course of the condition. The most important differential diagnostic procedure has proved to be ileocolonoscopy, since in addition to gross evaluation of the mucosa, targeted removal of biopsy specimens is also possible. PMID- 1855749 TI - [Surgical techniques in Crohn disease and ulcerative colitis]. AB - The usefulness of surgical treatment of inflammatory bowel disease is determined by the results that can be achieved. In Crohn's disease, in addition to minimal resections, non-resective procedures such as stricturoplasty, are also available for the treatment of acute and chronic complications. The operative treatment of peri-anal Crohn's lesions is determined by the acute or chronic complications that develop. Ulcerative colitis can be cured by complete removal of the colorectal mucosa, and malignant degeneration thus avoided. Continence-preserving colectomy with proctomucosectomy and ileo-anal pouch anastomosis obviates the need for a permanent ileostomy. PMID- 1855750 TI - [Conservative therapy of ulcerative colitis and Crohn disease]. AB - Basis treatment of severe ulcerative colitis and Crohn's disease comprises the systemic administration of corticosteroids. If the conditions are less severe, treatment with oral sulfasalazine or 5-aminosalicylic acid (5-ASA) can be attempted. Distal ulcerative colitis may respond to topical corticosteroids of enemas with sulfasalazine or 5-ASA. In long-term treatment with high-dose corticosteroids, azathioprine and 6-mercaptopurine may be employed to reduce the corticosteroid requirement. There ist no known generally applicable diet for the treatment or prophylaxis of these conditions. PMID- 1855751 TI - [Therapy of degenerative rheumatic diseases. Need for additional analgesic medication with Phytodolor N]. AB - In 40 inpatients with painful degenerative diseases, the additional requirement for nonsteroidal anti-inflammatory drugs (NAIDs) to obtain results identical with a given daily dose of either 3 x 30 drops of Phytodolor N or placebo administered over 3 weeks was investigated. Under Phytodolor N, a total of 100 mg of diclofenac and 1 tablet (500 mg) of paracetamol were additionally administered in 18 patients; under placebo, 2,400 mg of diclofenac and 3 tablets of paracetamol. In terms of days, additional medication was required on 3 days in the Phytodolor group, and on 47 days in the placebo group. Under Phytodolor N, the improvements obtained were identical to those in the group receiving in part considerably higher doses of NSAIDs and placebo. Clinical improvements are marked and major improvements (p less than 0.05) occur after only 1 week, with improvement being progressive. No side effects were observed. PMID- 1855752 TI - [Using activated macrophages for tumor therapy? Priv.-Doz. Dr. R. Andreesen presents new perspectives in cancer research. Interview by Elisabeth B. Moosmann]. PMID- 1855753 TI - [Ascariasis pancreatitis. Endoscopic diagnosis and therapy]. AB - Ascariasis lumbricoides is a parasitic disease of the human gastrointestinal tract. Migration of the worm through orifices and into ducts leads to such complications as cholangitis and pancreatitis; even bile duct perforation by Ascaris have been reported. Treatment of biliary ascariasis is usually surgical, although endoscopic removal of the worm has been successfully performed. We report on a case in whom an Ascaris worm in the common bile duct led to acute pancreatitis; the worm was successfully removed endoscopically after performing papillotomy. PMID- 1855754 TI - [Respiratory emergencies in childhood]. AB - The most important maneuvers of primary treatment of respiratory emergencies in childhood are the securement of free airways, provision of oxygen and (medicamentous) tranquilization of the child. The most common causes of these emergencies are fulminant (infectious) diseases of the upper and lower airways, a particularly significant aspect being the considerable mucosal swelling as compared with adults. Aspiration of foreign bodies is a further cause of acute, life-threatening respiratory distress. Treatment requires a systematic examination and circumspection to achieve in the shortest time adequate temporary improvement until more extensive measures can be performed in the hospital. PMID- 1855755 TI - [Psychosomatic aspects of inflammatory bowel diseases]. AB - The article reviews the most important psychosomatic aspects of inflammatory bowel diseases. It discusses aspects of etiology, coping with the disease and problems of psychotherapeutic treatment. At last the authors' special family therapy oriented consultation/liaison cooperation model with the gastroenterologists is described. PMID- 1855756 TI - [Chronic bowel diseases--is there a place for natural remedies?]. PMID- 1855757 TI - [TNF-alpha in allogeneic bone marrow transplantation. Significance for immunologic reconstitution, acute graft versus host disease and risk of complications after bone marrow transplantation]. AB - Follow-up studies on the release of tumor necrosis factor-alpha (TNF-alpha) in 114 patients confirm that this cytokine is released early in the course of endothelial complications, acute graft-versus-host disease, and interstitial pneumonitis following allogeneic bone marrow transplantation. Possible sources of systemic TNF-alpha activity are, in particular, tissue macrophages of the recipient type that are stimulated by pretransplant conditioning and endotoxin and subsequently further activated by interferon gamma released by donor lymphocytes. Consideration of these interactions permits the early recognition of high-risk patients, and suggests new strategies for prophylaxis and treatment of complications. PMID- 1855758 TI - [Clinical drug trials. Part 2. Legal regulations, (EG-) guidelines, ethics commission]. PMID- 1855759 TI - [Lipid metabolism disorders: diagnosis and treatment. 3: Treatment goals--therapy groups--primary hyperlipidemias. Nationale Cholesterin-Initiative]. PMID- 1855760 TI - [Meat as component of a balanced diet]. AB - From the point of view of the nutritionist, meat has an important role to play in supplying the body with proteins (essential amino acids, vitamins and minerals). There is no doubt that meat is the most valuable source of dietary iron. These facts make meat an important constituent of a balanced diet in a range of age and performance groups, including children and adolescents, pregnant women and nursing mothers, senior citizens and athletes. In the discussion about the nutritional/physiological quality of meat and meat products, total fat, cholesterol and purines must also be considered. About 80 g of lean meat per day, or a portion of about 150 g three times a week in patients with disorders of fat metabolism or elevated uric acid levels complies with the recommendations for low fat and low-cholesterol alimentation, and helps ensure a balanced diet. PMID- 1855761 TI - [Dermatomyositis--pathogenesis, diagnosis, therapy]. AB - Dermatomyositis is a rare systemic autoimmune disease that principally involves the skeletal muscles. Currently, the etiopathology is suspected to involve a viral infection with underlying genetic susceptibility, resulting in an abnormal immune reaction. Autoantibodies, in particular against enzymes involved in protein synthesis--especially aminoacyl-tRNA synthetases--appear to be found for the most part when the lungs are involved. Differential diagnosis is facilitated by the detection of various auto-antibodies. Treatment is unsatisfactory, and controlled studies, in particular when resistance to prednisone presents, are lacking. The prognosis depends, among other things, on the internal organs involved (heart, lungs, gastrointestinal tract, endocrine system). The search for viruses (e.g. hepatitis B) should be intensified using the latest, more sensitive, methods. PMID- 1855762 TI - [Lipid metabolism disorders: diagnosis and treatment. 4: Drug therapy and dietary recommendations. National Cholesterin-Initiative]. PMID- 1855763 TI - [Quality of life of hypertensive physicians with hypertension therapy. Randomized double-blind study of 237 female and male physicians with high blood pressure]. AB - In a group of 237 hypertensive male and female physicians, a placebo-controlled randomized double-blind, cross-over trial was performed to investigate the effects of the ACE inhibitor captopril on blood pressure and well-being. A thoroughly tested standardized measurement of well-being was employed. On the basis of the multivariate linear model, differences in the response to treatment (t-tests for cross-over differences) were investigated in terms of the seven parameters of well-being measured. In comparison with placebo, captopril (50 mg once daily) had a significant effect on five of the seven parameters. Thus, mood, general well-being, work performance, regeneration and quality of sleep all improved under treatment. It was also found that these improvements were not an immediate consequence of blood pressure reduction. The standardized evaluation employed here thus proved to be an informative additional evaluation criterion of antihypertensive therapy. PMID- 1855764 TI - Objectification of the severity of acute pancreatitis. PMID- 1855765 TI - Angio-CT: diagnosis and detection of complications of acute pancreatitis. AB - The ability of high-resolution, current-generation fast (sub-2 sec) CT scanners to display the precise cross-sectional anatomy of the pancreas and surrounding organs and structures had made it the most efficacious imaging modality for evaluation of patients with known or suspected acute pancreatitis. The use of angio-CT (automatic table incrementation, dynamic scanning mode, simultaneous intravenous infusion of a large bolus of contrast) has further extended its use for detection of parenchymal necrosis and vascular involvement. CT now plays a central role in diagnosis, prognostication (staging of severity of disease), detection of complications, and guidance for percutaneous techniques. PMID- 1855766 TI - Infected necrosis: morbidity and therapeutic consequences. AB - Some 20% of cases of acute pancreatitis are associated with pancreatic and/or peripancreatic necrosis. Mortality of necrotizing pancreatitis is higher than that of acute interstitial pancreatitis, especially if there is secondary pancreatic infection. Despite the fact that patients with infected necrosis are in general more seriously ill than those with sterile necrosis, it is not possible at present by any individual laboratory test or constellation of tests to determine precisely which patients are infected or will develop pancreatic infection. CT-guided percutaneous aspiration with bacteriological sampling continues to be a very safe, reliable method of distinguishing severe sterile pancreatitis from pancreatic infection. Improved survival for infected necrosis depends on earlier recognition and prompt effective surgical debridement. Necrosectomy and post-operative local lavage appear to improve survival in infected necrosis. PMID- 1855767 TI - Biliary acute pancreatitis. AB - Severe biliary acute pancreatitis is frequently associated with persisting bile duct stones, which has important implications with regard to management. In mild cases, cholecystectomy with operative cholangiography during the same admission is the treatment of choice. In patients with a severe attack, however, management remains controversial. There is increasing evidence to suggest that early biliary decompression with endoscopic sphincterotomy is associated with a lower morbidity and mortality than a conservative regime. In certain situations endoscopic sphincterotomy may also obviate the need to explore the common bile duct, and in high-risk patients may allow surgery to be avoided altogether. PMID- 1855768 TI - Conservative treatment of acute pancreatitis. AB - Most attacks of acute pancreatitis) have a favorable course and can thus be treated by conservative measures. The purpose of this review is: a) to present techniques (prognostic scores, computerized axial tomography, etc.) which can assist in the early identification of those cases of acute pancreatitis which can reasonably be submitted to non-surgical treatment; b) to summarize and discuss the main results of recent pharmaceutical research, and various conservative measures which have proven helpful in the treatment of this difficult disease. PMID- 1855769 TI - Operative management of necrotizing pancreatitis--necrosectomy and continuous closed postoperative lavage of the lesser sac. AB - In patients with severe acute pancreatitis, the most important diagnostic goal is differentiation between the interstitial-edematous and the necrotizing type of acute pancreatitis. Surgical management in patients with proven necrotizing pancreatitis is indicated in patients who develop surgical acute abdomen, sepsis, shock syndrome, multisystemic organ failure syndrome, persistent or progressive despite maximum intensive care. The most appropriate procedure for surgical management of pancreatic necrosis is the careful removal of necrosis and preservation of vital pancreatic tissue. Necrosectomy supplemented by postoperative closed continuous lavage of the lesser sac is a procedure that offers the advantages of debridement of devitalized tissue only, and the non surgical removal of necrotic tissue and bacterially and biologically active compounds. In comparison with a reoperation protocol, necrosectomy and continuous lavage reduce the reoperation rate as well as the need for tracheostomy. In a prospectively treated series of patients suffering from necrotizing pancreatitis, hospital mortality was 8.4% and the reoperation rate 27%. Any tissue becoming necrotic in the postoperative course of disease is rinsed with lavage fluid, thus obviating the need for repeated surgical reoperation in most patients. Local lavage is achieved by the insertion of two, in some cases five, large double lumen tubus and the use of 8 liters (median) of lavage fluid per day. PMID- 1855770 TI - Operative management of acute pancreatitis: ventral open packing. PMID- 1855771 TI - Beneficial effect of therapeutic infusion of nafamostat mesilate (FUT-175) on hemodynamics in experimental acute pancreatitis. AB - Acute pancreatitis was induced in 13 anesthetized dogs by retrograde injection of bile mixed with trypsin into the pancreatic duct. Six animals were treated with intravenous infusion of new synthetic antiprotease. Nafamostat Mesilate, at a dose of 1 mg/kg/h. Four out of seven untreated animals died during the experiment. All the treated dogs survived. Hemodynamic data were regularly monitored during a ten-hour observation period. Cardiac output, mean arterial pressure and left ventricular stroke volume decreased rapidly in the untreated animals. An increase in systemic vascular resistance and pulmonary vascular resistance was observed in dogs without treatment. Nafamostat Mesilate given as therapy significantly improved the hemodynamic parameters, and prevented the animals from developing shock. The study demonstrates an advantageous influence of synthetic antiprotease Nafamostat Mesilate on the course of acute experimental pancreatitis. PMID- 1855772 TI - Serum concentration and immunohistochemical localization of SPan-1 antigen in pancreatic cancer. A comparison with CA19-9 antigen. AB - We studied SPan-1 antigen in 64 patients with pancreatic cancer by measuring serum concentrations with RIABEAD and examining the intratumor staining patterns immunohistochemically. Serum concentrations were elevated (greater than 30 U/ml) in 46 patients (72.0%), roughly the same percentage as with elevated serum CA19-9 concentrations. Ten out of 19 patients without CA19-9 antigen expressed SPan-1, and the combined rate of positivity was 86% (55/64). Immunohistochemically, CA19 9 was localized to the apical surface and the supranuclear cytoplasm of normal epithelial cells, but SPan-1 was localized to the supranuclear cytoplasm or throughout the cytoplasm. After malignant degeneration, both antigens were found over the entire plasma membrane, throughout the cytoplasm (loss of polar distribution) and in the stroma surrounding the cells. SPan-1 was detected in 48 out of 54 adeno-carcinomas of the pancreas (89%), and all cases with an elevated serum concentration displayed stromal staining in the cancer tissues. The utility of SPan-1 antigen as a tumor marker for diagnosing pancreatic cancer was found to be equal to that of CA19-9. PMID- 1855773 TI - Mucin-producing cells and endocrine cells of gallbladder epithelium in patients with uncomplicated cholelithiasis. AB - In this study we have investigated various morphofunctional features of gallbladder mucosa in patients with uncomplicated cholelithiasis. The histological changes, endocrine cell types and their distribution, and mucin producing cells were characterized by immunocytochemistry and mucin histochemistry; moreover, we attempted to correlate these findings to the number and size of gallbladder stones and the type of bacteria present in the bile. Our results indicate that, despite similar clinical parameters, a wide range of histological changes can occur in the gallbladder mucosa of these patients. Moreover, the presence of certain endocrine and mucin-producing cell types in so called "pyloric metaplasia" led us to hypothesize that this finding may be a trivial event in the gallbladder epithelium. PMID- 1855774 TI - Percutaneous transhepatic biliary drainage--twelve years' experience. AB - Our experience with percutaneous transhepatic biliary drainage in a total of 362 patients carried out between January 1977 and December 1988 is described. Three hundred and fifty drains were correctly placed, and results were good in 285 (81.5%), fair in 53 (15.1%) and poor in 12 (3.4%). In 12 of the total number of cases (3.4%) it was not possible to position the drain effectively. The mortality rate of the method was 0.8% (3 cases). Complications were as follows: obstruction 7 (1.9%), dislodgement 15 (4.1%), hemobilia 15 (4.1%), hemoperitoneum 1 (0.2%), cholangitis 6 (1.6%), and choleperitoneum 10 (2.7%). In view of the good results and low incidence of complications the conclusion is that in skilled hands, percutaneous transhepatic biliary drainage is a very useful method that should be available in any center specializing in hepatobiliary surgery. PMID- 1855775 TI - Is exocrine pancreatic cancer a hormone-dependent tumor? A study of the existence of sex hormone receptors in normal and neoplastic pancreas. AB - The 5-year survival rate of patients with exocrine pancreatic cancer after surgery is less than 5%, in patients treated with radical surgery, with or without adjuvant therapy. It has been well documented clinically and experimentally that sex hormones influence the physiology of the exocrine pancreas. Hormone manipulation inhibits the growth of human pancreatic cancer in nude mice. Several nonrandomized studies have suggested the efficacy of antihormone therapy in the treatment of advanced pancreatic cancer. However, the existence of sex hormone receptors in exocrine pancreatic cancer has been a matter of controversy. This study was designed to investigate the presence of sex hormone receptors (estrogens, progesterone and androgens in normal pancreas and exocrine pancreatic cancer, using two different methods: immunohistochemistry and enzyme immunoassay. Twenty-eight biopsies of normal pancreas and 15 biopsies of exocrine pancreatic cancer were studied. Estrogen receptors and progesterone receptors were measured by enzyme immunoassay, using specific monoclonal antibodies. Androgen receptors were determined by radioligand assay. Sixteen biopsies of normal pancreas and 12 biopsies of exocrine pancreatic cancer were studied by immunohistochemistry. In exocrine pancreatic cancer we could not detect estrogen receptors or progesterone receptors, either by enzyme immunoassay or immunohistochemistry. Androgen receptors were always negative (less than 2 fm/mg). In the normal pancreas, 5 out of 28 cases showed increased levels of progesterone receptors (greater than 10 fm/mg) as measured by enzyme immunoassay. Immunohistochemistry revealed progesterone receptors in the pancreatic islets of 16 normal pancreases studied. Nuclear staining was observed in more than 70% of the cells. Estrogen receptors were always negative by immunohistochemistry and enzyme immunoassay in the normal pancreas.2+n PMID- 1855776 TI - Modern techniques in the diagnosis and treatment of gastrointestinal and biliary tree parasites. AB - Parasitic infestations are endemic in tropical and subtropical areas, but rarely occur in temperate zones, and are imported by tourists, immigrants and expatriates. Gastrointestinal and biliary tree parasites are the commonest helminthics in humans. Previously these were diagnosed only by stool examinations, but recently other diagnostic techniques have been used. These include fibreoptic endoscopies for upper or lower gastrointestinal tract and biliary tree. Endoscopy plays an important role in diagnosis, treatment and follow-up as in gastric anisakiasis, chronic giardiasis, strongyloides, hepatosplenic and chronic intestinal schistosomiasis. ERCP is diagnostic in biliary tree obstruction due to parasites or associated stones or cholangiocarcinoma; worm extraction will lead to biliary decompression. Endoscopic instillation of drugs such as mepa-crine in chronic giardiasis, piperazine in biliary ascariasis and hypertonic saline in a ruptured hydatid liver cyst. Imaging techniques, such as barium studies, ultra-sound, CT and MRI, play an essential part in investigations and follow-up in parasitic disease. Therapeutic techniques under ultrasound or CT guidance for amoebic liver abscess or recent percutaneous drainage of hydatid cyst of the liver have been done successfully. PMID- 1855777 TI - Pathology and pathogenesis of toxic (alcoholic) liver disease. PMID- 1855778 TI - Acute pancreatitis--a challenge to gastroenterologists and surgeons. PMID- 1855779 TI - Surgery in acute pancreatitis. AB - The most important diagnostic step in the management of patients with severe acute pancreatitis is discrimination between interstitial-edematous pancreatitis and necrotizing pancreatitis. In this respect, laboratory measures like CRP, LDH, and antiproteases, and the application of contrast-enhanced CT are highly sensitive methods. Surgical decision-making should be based on clinical, bacteriological and contrast-enhanced CT data. Persistent or progressive systemic or local organ complications occurring despite ICU treatment for a minimum of three days are indicators for surgical management of necrotizing pancreatitis. Patients suffering from sepsis syndrome, cardiovascular shock, multisystemic organ failure syndrome, or surgical acute abdomen should be treated surgically early in the course of the disease. The use of a major pancreatic resection for the surgical management of necrotizing pancreatitis should be excluded from treatment protocols. Carefully performed necrosectomy or debridement, in combination with continuous or repeatedly applied surgical evacuation techniques for necrotic tissue, bacteria, and biologically active compounds, has proved to be very effective in experienced treatment centers. Necrosectomy and postoperative continuous local lavage is a well-adapted, safe, and atraumatic procedure. It results in a hospital mortality of less than 10% in patients with necrotizing pancreatitis. PMID- 1855780 TI - Clinical picture and diagnosis of acute pancreatitis. AB - Acute pancreatitis is characterized by clinical, morphological, and functional aspects. Severe abdominal pain with progression during the first hours after onset is the leading symptom. In the majority of patients acute pancreatitis had a "mild" clinical course, but 10 to 20% will develop severe local and systemic complications. Symptoms at the onset of disease are not specific and need consideration of several other diagnoses. Elevation of pancreatic serum enzymes is the main parameter in the diagnosis of acute pancreatitis. Besides the traditional parameter of total amylase, several specific pancreatic enzymes (e.g. pancreatic amylase, lipase, immunoreactive trypsin or elastase) are now widely used in clinical routine and guarantee a higher diagnostic specificity. The imaging procedures ultrasonography and computed tomography aid in identifying etiological factors in grading the severity of the disease and deciding therapeutic strategies. Endoscopic retrograde chol- angiopancreatography is most sensitive in detecting biliary lithiasis and can be successfully complemented by sphincterotomy if needed. Besides complex clinical and laboratory criteria, several biochemical markers (e.g. C-reactive protein, PMN-elastase, trypsinogen activation peptides) have been found to be valid for the detection of pancreatic necrosis and are of definite prognostic value. On the basis of such detailed information, the therapeutic strategy can be planned in a straight-forward manner. PMID- 1855781 TI - CHE1 UF serum cholinesterase phenotype in whites and non-whites from southern Brazil as determined by a new method. AB - A sample of 251 Whites and 818 Non-Whites, from Curitiba (southern Brazil), was typed with a new method with the aim of estimating the frequency of the CHE1*F allele. The frequency of this allele did not differ between Whites (0.60 +/- 0.34%) and Non-Whites (0.49 +/- 0.17%), being estimated as 0.51 +/- 0.15% for the whole sample. The use of the inhibitors DL-propranolol and RO2-0683 with alpha naphthylacetate as substrate (at 37 degrees C) was efficient for discriminating between the CHE1 U and CHE1 UF phenotypes. PMID- 1855783 TI - C1R subcomponent polymorphism in Japanese: description of a new allele. AB - The polymorphism of C1R was investigated in 570 unrelated Japanese individuals using isoelectric focusing and immunoblotting. A total of 11 different C1R phenotypes including a new pattern designated C1R 11-1 were observed. The allele frequencies were C1R*1 = 0.4561, C1R*2 = 0.3377, C1R*5 = 0.1956, C1R*8 = 0.0088 and C1R*R (C1R*9 and C1R*11) = 0.0018. The population data fitted the Hardy Weinberg equilibrium. The C1R polymorphism in Japanese was shown to be controlled by 3 common alleles, C1R*1, C1R*2 and C1R*5, as compared to Caucasians where only the former 2 are present commonly. This complement system can be a useful genetic marker for anthropological studies. PMID- 1855782 TI - Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Iowa Lipid Research Clinics family study. AB - The aggregation of lipids [total cholesterol (CH) and triglyceride (TG)] and lipoproteins [high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL)] in families ascertained through random and nonrandom probands in the Iowa Lipid Research Clinics family study was examined. Nonrandom probands were selected because their lipid levels (at a prior screening visit) exceeded a certain pre-specified threshold. The statistical method conditions the likelihood function on the actual event that the proband's value is beyond the threshold. This method allows for estimation of the path model parameters in randomly and nonrandomly ascertained families jointly and separately, thus enabling tests of heterogeneity between the two types of samples. Marked heterogeneity between the random and the hyperlipidemic samples is detected in the multifactorial transmission for TG and HDL, and moderate heterogeneity is detected for CH and LDL, with a pattern of higher genetic heritability estimates in the random than nonrandom samples. The observed pattern of heterogeneity is compatible with a higher prevalence in the random sample of certain dyslipoproteinemias that are associated with nonelevated lipids. For the random samples, genetic heritabilities are higher for CH and HDL (about 60%) than for TG and LDL (about 50%). For the nonrandom samples those estimates are about 45, 40, 35 and 30% for HDL, CH, LDL and TG, respectively. Little to no cultural (familial environmental) heritability is evident for CH and LDL, although 10-20% of the phenotypic variance is due to cultural factors for TG and HDL. These results suggest that the etiologies for lipids and lipoproteins may be quite different in random versus hyperlipidemic samples. PMID- 1855784 TI - Plasminogen polymorphism in Libyans: description of a new rare variant. AB - The genetic polymorphism of human plasminogen (PLG) was investigated in Libyans using wide-scale ultrathin-layer polyacrylamide isoelectric focusing with subsequent immunoblotting. The 2 common alleles, PLG*A and PLG*B, and 4 previously reported rare ones, PLG*A3, PLG*M4, PLG*B1 and PLG*B2, were observed. In addition, a new intermediate rare allele designated PLG*MTripoli (PLG*MT) was encountered. The estimated allele frequencies for the genes PLG*A, PLG*B, PLG*A3, PLG*MT, PLG*M4, PLG*B1 and PLG*B2 were 0.6409, 0.3091, 0.0182, 0.0045, 0.0091, 0.0045 and 0.0136, respectively. The isolated probability of exclusion in cases of disputed paternity among Libyans is 23.3%. PMID- 1855785 TI - Immunological studies of families segregating the silent gene for plasma cholinesterase. AB - Seven families segregating apparently silent gene homozygotes have been investigated by enzyme-linked immunosorbent assays. These families confirm not only the heterogeneity of the silent gene in the form of E1s and E1t but in 3 families there is support for the segregation of the new gene E1x. PMID- 1855786 TI - High prevalence of haemoglobin E in three populations of the Malda district, West Bengal, India. AB - High frequencies of haemoglobin (Hb) E were reported earlier from Assam in northeast India. In the present study one of the three populations of the Malda district of West Bengal, called the Deshi, was found to show one of the highest incidences of the Hb E gene (0.61) recorded so far. A founder effect and/or local inbreeding may possibly explain this observation. PMID- 1855787 TI - Genetic polymorphism of alpha-2-HS-glycoprotein: four new alleles and allele frequencies in Japanese. AB - alpha 2-HS-glycoprotein (AHSG) phenotyping was done in 655 Japanese from the Goto Islands, western Japan, using isoelectric focusing followed by immunoblotting. Four new AHSG alleles were encountered, AHSG*G1-G4, whose genetic transmissions were established in family studies. The allele frequencies were: AHSG*1 = 0.7221; AHSG*2 = 0.2748, and AHSG*G1-G4 = 0.0008, respectively. PMID- 1855788 TI - Acid phosphatase, adenosine deaminase and esterase D polymorphisms in the Spanish Basque population. AB - The 3 red-cell polymorphic systems acid phosphatase (ACP), adenosine deaminase (ADA) and esterase D (ESD) have been studied in a random sample of 1,112 individuals from the Basque country: The allelic frequencies obtained were ACP*A = 0.275, ACP*B = 0.718 and ACP*C = 0.007; ADA*2 = 0.021, and, ESD*2 = 0.066. The allelic frequencies have been compared with those of other Basque and other European populations. In comparison with Basques, significant differences were detected only for ACP, whereas as regards other Europeans significant differences were obtained with practically all the populations compared for the 3 genetic systems studied. The low values of the less frequent alleles, especially that for the ACP*C allele which is the lowest reported in Europe, are noteworthy. PMID- 1855789 TI - Biomedical engineering in dentistry. PMID- 1855790 TI - CAD/CAM for dental restorations--some of the curious challenges. AB - Computer-aided design and manufacturing for dental restorations has opened a new world of possibilities--some that appeal to engineers and clinicians and some that have created some interesting challenges. The objective of this overview is to briefly describe a system being developed by the Universities of Maryland and Minnesota which is capable of producing dental crowns. Some of the challenges and difficulties that have arisen during the development activities will be addressed. The final focus will be on some of the questions that, because of the new technology, can now be addressed and are presenting new challenges. PMID- 1855791 TI - Computer-controlled differential scanning calorimetry of dental composites. AB - In this paper, computer-controlled differential scanning calorimetry has been used to evaluate the heat liberated and the temperature rise associated with the light cure of selected dental composites. In addition, the effect of postcure heating and increased ambient temperature of light cure are examined in terms of potential secondary cure. The results indicate significant differences between the mean heats of cure of different composites, primarily reflecting the filler fraction variations of the composites. In addition, increased cure activity appears to result from both postcure heating as well as thermal activation due to higher ambient temperature of light cure. The results are analyzed and attributed to variations in resin phase composition and resin content per unit weight of composite as well as thermally induced enhancement of cure. PMID- 1855792 TI - Nonlinear interpolation of mandibular kinesiographic signals by applying sensitivity method to a GMDH correction model. AB - The purpose of the present paper was to propose an improved nonlinear interpolation method for estimating distorted kinesiographic recording of interlattice points in space, and to evaluate its correction accuracy. The group method of data handling (GMDH) correction method we have reported previously is essentially different from other geometric correction methods in the sense that the GMDH correction model can be adapted to the measurement environment in which kinesiographic signals are subject to ferromagnetic interferences. Due to its inherent structure, however, our previous GMDH correction model was restricted to kinesiographic signals representing lattice points in space. In this paper, we explored the sensitivity method for GMDH correction modeling. This provides for nonlinear interpolation of kinesiographic signals for interlattice points. Nominals, i.e., true values, of 3-D coordinates of the interlattice points were determined by means of a mandibular jaw movement simulator together with simultaneous recording of distorted kinesiographic signals which corresponded to the nominals. Distorted signals were corrected by the new method of correction modeling. A mean estimation error of 0.16 mm (SD 0.19 mm) was determined for 24 interlattice coordinates. Thus, nonlinear interpolation by the sensitivity method was confirmed to be effective. PMID- 1855794 TI - Computer-aided interpretation and quantification of angular periodontal bone defects on dental radiographs. AB - Capabilities of human observers to detect and describe small bone defects objectively are limited. Digital image processing can provide a useful contribution to the diagnostic process. This paper describes the evaluation of a computer-aided procedure for the interpretation and quantification of angular periodontal bone defects on dental radiographs. The computer-aided procedure was able to rank series of artificial periodontal bone lesions as accurate as experienced clinicians. Comparison of data from clinical inspection of lesions during surgery and quantitative results of the digitized procedure shows that the latter produced reliable information on the lesions size. Reproducibility is satisfactory. It was concluded that computer-aided detection and description of periodontal bone defects decreases the interobserver variability in general and the time-dependent variability in repeated assessments of a single observer. PMID- 1855793 TI - A periodontal probe with automated cemento--enamel junction detection-design and clinical trials. AB - An automated periodontal probe has been developed to measure pocket depth and attachment loss in a single measurement under controlled force conditions. A natural anatomic landmark, the cemento-enamel junction (CEJ), is used as a reference for attachment level measurements. The CEJ is detected automatically by immediate digital postprocessing of simultaneous measurements of probe tip acceleration and displacement during probing. Clinical trials in the beagle dog model for naturally occurring periodontitis have shown that the automated probe, when used with 35 g probing force, has a repeatability of 0.16 mm and a bias of 0.09 mm. These results indicate that the automated periodontal probe is capable of attachment level measurements with a high degree of repeatability and validity. PMID- 1855795 TI - An artificial oral environment for testing dental materials. AB - Two servo-hydraulic actuators were combined to produce the force movement cycle of human mastication. A closed-loop method of control was used which functions in a manner similar to the human neuromuscular system. The horizontal closed-loop uses a linearly variable differential amplifier (LVDT) to monitor the position. The vertical closed-loop uses both an LVDT to monitor position and a load cell to monitor force with a "mode switch" being made between the two mechanisms of control. A function generator is used to produce a sine wave which is modified to produce the movement and force programs for the two servo-hydraulic actuators. An acrylic chamber was constructed which contains the test samples and maintains an environment similar to that which occurs in the mouth. Natural or artificial saliva maintained at 37 degrees C is continuously circulated through the chamber. The time to complete a single chewing cycle was decreased by eliminating that part of the cycle where no force is produced. This enables the chewing rate to be increased to four cycles per second. The wear produced in the artificial mouth was found to have a high correlation with clinical wear if 250,000 cycles in the artificial mouth are assumed to be equivalent to one year in the human mouth. PMID- 1855796 TI - Optical determination of dental pulp vitality. AB - In this preliminary study, we explored the feasibility of employing photoplethysmography and pulse oximetry to assess the status of the blood circulation in the dental pulp. A simple photometer that measures diffuse light transmission at 575 nm was built to record tooth plethysmograms, and the ability to distinguish vital from surgically devitalized teeth of a dog using plethysmography was demonstrated. As an extension of the photoplethysmographic technique, red-infrared pulse oximetry applied to the measurement of the oxygen saturation (SO2) of blood in the pulp was also examined using an in vitro test setup. Results suggest that the measurement of relative SO2 changes is feasible, but standard dual-wavelength pulse oximetry does not enable determination of SO2 independent of tooth geometry and sensor placement. PMID- 1855797 TI - pH measurements with an ion sensitive field effect transistor in the mouth of patients with xerostomia. AB - A transistor pH electrode (ion sensitive field effect transistor), placed in the upper dentures of eleven xerostomia patients and five healthy volunteers, was used to register pH changes in five-, six- and seven-day-old dental plaque. A mouth rinse with a 10% sucrose solution caused a pH fall of about three decades. A significant difference in duration of critical plaque pH was observed: in xerostomia patients, a 10% longer period of pH less than 5.7 was registered during 60 min following a sucrose rinse. Normal oral functions were not influenced by the denture with an integrated electrode. This method is usable for plaque pH registration in xerostomia patients. PMID- 1855798 TI - Application of digital image analysis in dental radiography for the description of periapical bone lesions: a preliminary study. AB - This paper describes an application of digital image analysis for the description of periapical bone lesion in dental radiography. These techniques enable the problem of observer variability to be circumvented, and can eventually be used for the quantitative assessment of bone lesions. Since periapical bone lesions appear radiographically as dark areas compared with their surrounding tissues, an edge-detection method was developed to extract the boundaries between anatomy and pathology. The original data were transformed in such a way that only the outlines remained. The lesion was assumed to be demarcated by a continuous outline, so all the contour points not being part of a continuous outline were excluded. With only limited operator interaction, the lesion contour could be projected successfully onto the original image. The result of this operation was a simplified diagnostic examination process promising a higher degree of objectivity in periapical bone lesion detection. It is concluded that the results encourage further development of image processing techniques suitable for the definitive detection and diagnosis of periapical bone lesions. PMID- 1855799 TI - Measurements of dental cast profile and three-dimensional tooth movement during orthodontic treatment. AB - We have developed a system for measuring three-dimensional profiles of dental casts and three-dimensional tooth movement during orthodontic treatment. The profile measurement is based on the triangulation method which detects a laser sport on a cast using an image sensor. The system is computer-controlled and designed to achieve the depth and lateral resolutions of 0.05 and 0.1 mm, respectively, within a depth range of 25 mm. We have applied our system to measuring three-dimensional movement of teeth, including rotations, during orthodontic treatment. The movements have been obtained by means of three dimensional registration of tooth profiles using a computer between casts serially taken at different stages of the treatment. Measurements over periods of 41 to 190 days on patients have revealed that this technique is capable of quantifying the difference in movements due to orthodontic therapeutics. PMID- 1855800 TI - Real-time sensing of tooth position for dental digital subtraction radiography. AB - Dental digital subtraction radiography requires accurate repositioning of the patient and X-ray source in order to facilitate correct diagnostic of bone loss. Present mechanical repositioning systems do not allow radiography of posterior teeth, and are uncomfortable for the patient. A new repositioning system that utilizes a six degrees of freedom position sensor and a robot arm with X-ray source is proposed. A mathematical model for the system is given, and the robot arm solution is obtained based on patient position. An error analysis is performed in order to determine the influence of sensor and robot errors on system accuracy. A series of experiments to determine sensor noise and accuracy are described. These tests showed relatively small errors over the work envelope of the sensor. Further tests showed that there is no adverse effect due to the presence of metal work in the patient's mouth. The high bandwidth of the sensor may allow real time tracking of small movements of the patient's head. PMID- 1855801 TI - A beamformer for the acquisition of evoked potentials. AB - Evoked potentials (EP) contain information about various physiological parameters and the estimation and detection of these signals can aid in the diagnosis of many pathological conditions. However, the signal-to-noise ratio (SNR) for EP measurement is often very low, and thus signal processing techniques must be employed to enhance the SNR. A delay and sum beamformer acquisition system has the potential for significant SNR improvement in EP measurements. In this communication it is shown that an electrode array acquisition system implements a uniform coherent delay and sum beamformer. The performance of the beamformer is characterized in terms of the number of electrodes, and cross-channel correlation. When compared to conventional ensemble averaging, the beamformer reduces the number of response repetitions required to achieve a given SNR by a factor which approaches the number of channels in the acquisition system. PMID- 1855802 TI - Reconstruction of out-of-plane cardiac displacement patterns as observed on the chest wall during various phases of ECG by capacitance transducer. AB - The out-of-plane displacements due to cardiac action have been measured on the chest wall by an electronic distance measurement technique which is based on the variation of the capacitance between the probe and moving surface. The displacements were measured at 36 locations over the entire cardiac region along with ECG and were directly fed to an IBM PC/AT computer after A/D conversion. From these data, the displacement patterns for the whole region during the complete cardiac cycle could be reconstructed in a perspective view. The sequential analyses of the displacements shows the details of the cardiac events and the results obtained are in agreement with other techniques. The averaged displacements over various regions of the heart for normal subjects have also been presented. PMID- 1855804 TI - Comments on "Point source nerve bundle stimulation: Effects of fiber diameter and depth on simulated excitation". PMID- 1855803 TI - A qualitative approach to cell growth modeling and simulation for cancer chemotherapy. AB - A qualitative model of cell growth, based on qualitative process theory, is presented. The model can be used to analyze the effects of the interaction of antiproliferative drugs on cells when the effects of each specific drug are known, mainly when designing multi-drug protocols for optimal cancer treatment. PMID- 1855805 TI - You're right if you think that there has been a dramatic increase in the size of dental practices. PMID- 1855806 TI - [Infectious endocarditis]. PMID- 1855807 TI - [Microbial spectrum and microbiological diagnosis of infectious endocarditis]. AB - Still streptococci play the most important role as causatives of infective endocarditis. As change in composition of patient groups has taken place gradually pathogens like Staphylococcus epidermidis, enterococci, gram-negative rods and Candida species become more and more important now. Providing high-level accuracy if applied according to current rules blood culture is yet the basis for endocarditis caused by popular bacterial pathogens. If infection due to Candida species is suspected additional measuring of antibody response may be helpful in supporting the tentative diagnosis. Rare pathogens like Rickettsiae and Mycoplasma sp. must be considered for differential diagnosis, as infections caused by these organisms are to be identified by serological methods in first line. PMID- 1855809 TI - [Therapy and prophylaxis of infectious endocarditis]. AB - Infective endocarditis remains even today a potential lethal disease. The most frequent bacterial agents are viridans streptococci, staphylococci and enterococci. Left-sided endocarditis predominates except for patients with drug addiction. Modern recommendations of treatment are based on in vitro studies, experimental data from the animal model and clinical studies. Antimicrobial therapy should be parenteral and bactericidal in character. Detailed recommendations for treatment are given. Progressive heart failure, persistent bacteremia and repeated embolism are the most important reasons for surgical intervention. Modern prevention is performed as single or short-term prophylaxis for about sixteen hours. Simple practicability as well as handing out of guidelines to the patient will contribute to improved acceptance. PMID- 1855808 TI - [Clinical aspects of endocarditis]. AB - Considering the incidence of infectious endocarditis this disease is still an important clinical entity in internal medicine departments. Leading symptoms are fever, cardiac murmurs, embolic phenomena, skin alterations and also sometimes CNS-disturbances. Two different clinical endocarditis entities can be separated: an acute aggressive course of endocarditis and the subacute course (endocarditis lenta). Diagnostic procedures are mainly based on positive blood cultures and echocardiographic detection of cardiac vegetations. In case of a progressive development of cardiac insufficiency, non treatable infection, large vegetations on valve and embolic phenomena a prosthetic valve implantation is indicated. PMID- 1855810 TI - [Microbial pathogenicity factors and host defense mechanisms--parameters of post traumatic infections]. AB - The clinical features of posttraumatic infections are due to the interactions between microbial pathogenicity factors and the host defense. The virulence mechanisms of microorganisms include the adherence, chemotaxis, invasion, resistance, and production of toxins. In addition, the humoral and cellular components of the immune system are impaired in trauma patients. The influence of pathogenic microorganisms on immune effector cells results in the release of various inflammatory mediators which participate in the protective host response to infection but induce local and systemic damage provided they are excessively produced and/or ineffectively metabolized. PMID- 1855812 TI - [Systemic lupus erythematosus (SLE) with panniculitis and rhabdomyolysis]. AB - In systemic lupus erythematosus as a multi-system disease the involvement of skeletal muscle has been described as a rather mild polymyositis, myopathy or inclusion-body myositis. Here we present a patient with a severe lupus presenting with a fulminant myositis with rhabdomyolysis and panniculitis. PMID- 1855811 TI - [Cyclophosphamide pulse therapy of systemic lupus erythematosus with renal involvement]. AB - Study design and preliminary data of a prospective randomized trial with monthly administration of intravenous cyclophosphamide in so far 12 patients with systemic lupus erythematosus (SLE) and nephritis are presented. PMID- 1855813 TI - [Three cases of chronic polyarthritis after silicon implantation (breast augmentation): causal relationship?]. AB - We describe three women with rheumatoid arthritis after augmentation mammoplasty with silicone implants. The possibility for a causal relationship between silicone implantation and arthritis as examples of a "human adjuvant disease" is discussed. PMID- 1855814 TI - [Induction of autoreactive T-cells by bacterial stress proteins in HLA-DR4 donors]. AB - From the peripheral blood of HLA-DR4+ healthy donors or patients with rheumatoid arthritis autoreactive T-cell lines were obtained after stimulation with bacterial heat-shock protein. All lines obtained express an alpha/beta-T-cell receptor and they are predominantly CD4+. The determination of the fine specificity of those autoreactive T cells showed, that either amino-acid position #71 or #86 of the HLA-DR beta 1 chain was critical for recognition by the antigen receptor. PMID- 1855816 TI - Colinearity of novel genes in the class II regions of the MHC in mouse and human. AB - To examine the degree of conservation of gene organization in and around the class II regions of the major histocompatibility complexes of mouse and human, we have established the positions of sequences homologous to five human non-class II genes (RING1-5) in mouse, and the positions of sequences homologous to three mouse non-class II genes (KE3-5) in human. The resulting comparative map reveals that the organization of genes in the entire proximal region of the MHCs of mouse and human is remarkably conserved, apart from the H-2K gene pair in mouse, which can be accounted for by a 60 kilobase (kb) insertion. The characterization of the novel human gene RING5 is also presented. This gene, which is widely expressed, maps 85 kb proximal to the DPB2 gene. Partial nucleotide sequencing of a RING5 cDNA clone reveals that it is the human homolog of the mouse KE4 gene. PMID- 1855815 TI - The role of C5 and T-cell receptor Vb genes in susceptibility to collagen-induced arthritis. AB - Collagen-induced arthritis (CIA) is a rodent arthritis model in which immunization with heterologous type II collagen induces an inflammatory polyarthritis. Susceptibility to the disease is mediated by major histocompatibility complex (MHC) genes as well as genes at other loci. Previous studies of the SWR/J mouse strain, which is resistant to CIA despite bearing the susceptible H-2q haplotype, have suggested that this resistance is the result of a deletion of T-cell receptor (Tcr) Vb gene segments which is carried by this strain. Other studies have implicated a deficiency in complement component C5 as the cause for the resistance. In order to assess the relative importance of these two genes in susceptibility to CIA, and to provide an estimate of the number of independent genes involved in the disease, we analyzed 196 F2 progeny of a (DBA/1 x SWR/J) cross for arthritis susceptibility, and expression of both C5 and Tcr genes. Thirty of the F2 progeny developed arthritis. All of the arthritic mice had at least one copy of the wild-type C5 allele, while the Tcr-Vb haplotypes were distributed in Mendelian fashion. These results demonstrate that C5 sufficiency is an absolute requirement for CIA, but that Tcr-Vb genes located within the SWR deletion have little influence. Genetic analysis of the incidence rate suggests that there is polygenic control of susceptibility to CIA and that in addition to H-2, 5-6 other independent loci (including C5) may be involved. PMID- 1855817 TI - Nonobese diabetic and nonobese nondiabetic mice have unique MHC class II haplotypes. PMID- 1855818 TI - Major histocompatibility complex (MHC) class II region in humans. PMID- 1855819 TI - Isolation of mosquito-pathogenic Bacillus sphaericus & B. thuringiensis from the root surface of hydrophytes. AB - Attempts were made to isolate B. sphaericus and B. thuringiensis active against mosquito larvae from the root surface of hydrophytes. Out of 139 samples processed, 86 B. sphaericus and 23 B. thuringiensis isolates were obtained. Sixty two of the B. sphaericus isolates belonged to the serotype H5a5b, 2 to H6 and 22 isolates did not agglutinate with any of the 6 antisera tested. Twenty of the B. thuringiensis isolates belonged to the H14 serotype, 1 each to the H10 and H17 serotype(s) and 1 to an unknown serotype. Fifty nine of the B. sphaericus and 20 of the B. thuringiensis isolates fall under highly toxic category with the LC50 dose of 1-50 ng/ml for Culex quinquefasciatus third instar larvae. PMID- 1855820 TI - Psychiatric morbidity in HIV infected individuals. AB - Forty six subjects infected with the human immunodeficiency virus (HIV) were followed up, for recording psychiatric morbidity if any, before and after the information regarding their HIV status was revealed to them. Among these, four patients had the AIDS syndrome, while 42 individuals were HIV carriers. The pre information morbidity in the AIDS group included two individuals who presented with delirium and one with an adjustment disorder. The psychiatric diagnosis among the HIV carriers revealed one patient with major depression, four with adjustment disorders and four with alcohol dependence syndrome. The additional morbidity after the diagnoses was revealed included major depression and adjustment disorders which could be managed by psychological intervention and counselling in most cases. The individual who developed major depression later, committed suicide. The study though preliminary in nature, suggests that it may be beneficial to include psychiatric management as part of the general care of individuals with HIV infection. PMID- 1855821 TI - In vitro effect of Phyllanthus amarus on hepatitis B virus. AB - To evaluate the effects of P. amarus on hepatitis B virus (HBV) antigens and HBV DNA, initial ethanolic extract and subsequent fractions of the plants were prepared. The whole plant material was dried, powdered and extracted with alcohol and subsequently fractionated in hexane, chloroform, butanol and finally in water. All the material were tested for in vitro effects on HBsAg, HBeAg and HBV DNA in serum samples positive for HBV antigens followed by the screening of respective antigens by Elisa. HBV-DNA was determined by molecular hybridization. The extracts were effective against HBV antigens, the butanol extract being the most potent. Further chromatographic fractions showed an enhanced activity. The active fractions inhibited the interaction between HBsAg/HBeAg and their corresponding antibodies suggesting anti-HBs, anti-HBe-like activity and also an effect on HBV-DNA. PMID- 1855822 TI - Prevalence study of tuberculous infection over fifteen years, in a rural population in Chingleput district (south India). AB - As in the earlier BCG trial against tuberculosis conducted in Chingleput district in south India (in 1969), the entire study population was tuberculin tested (Survey I), a study was undertaken subsequently to see whether in this population there was any change in the tuberculosis situation in terms of prevalence of infection in children. For this purpose, in two of the panchayat unions, in a random sample of panchayats, tuberculin testing was repeated twice at an interval of 10 yr (Survey II) and 15 yr (Survey III) after the initial testing in children aged 1-9 yr. High coverages were obtained for tuberculin testing and reading. Data from 8,703 and 9,709 children at Surveys I and II respectively was used for comparing the prevalence of infection over a period of 10 yr and from 4,808, 4,965 and 4,889 children at Surveys I, II and III respectively for comparing the prevalence of infection over a period of 15 yr. The results showed that although the prevalence of infection varied in the two panchayat unions, within each panchayat union it did not differ significantly at the three surveys. The overall prevalence of infection at the three surveys was 9.0, 10.2 and 9.1 per cent respectively. The average annual risk of tuberculous infection was estimated to be 1.7, 1.9 and 1.7 per cent at the three surveys respectively. Thus, the results clearly showed that, over a period of 15 yr, there was no change in the tuberculosis situation, in terms of prevalence of infection, in the study population. PMID- 1855823 TI - Enterotoxigenic Campylobacter jejuni & C. coli in the etiology of diarrhoea in northern India. AB - Faecal specimens from subjects with (320) and without (450) diarrhoea were screened for Campylobacter jejuni and C. coli. C. jejuni and C. coli were detected in 5 per cent of subjects with diarrhoea and 0.7 per cent of those without diarrhoea and the difference was significant (P less than or equal to 0.01). The isolation rate was much higher in under five diarrhoeal children (8.3%), in comparison to the older group (3.0%). Eleven diarrhoeal isolates of C. jejuni and C. coli were tested in rat ileal loops for enterotoxigenicity. All the strains caused fluid accumulation in the loop model. However, 6 strains required up to 3 consecutive passage(s) to do so. Therefore, rat ileal loops were found to be sensitive and reproducible animal model for the demonstration of enterotoxin produced by C. jejuni and C. coli. The culture filtrates of 3 strains of C. jejuni and C. coli were subjected to neutralisation with cholera antitoxin. The fluid accumulation was completely neutralised up to 1 in 80 dilution showing immunobiological relationship between C. jejuni and C. coli enterotoxin and cholera toxin. PMID- 1855824 TI - Simplified method for the detection of DNA hydrolysis by enteric campylobacters. AB - A simplified medium was developed for the detection of DNase produced by enteric campylobacters. Sensitivity and reproducibility of the test were similar to that of the improved toluidine blue DNA agar method. Logistically, the simplified DNA hydrolysis test was cheaper (5.5 times) than the earlier medium. Based on this study we recommend the routine use of the simplified medium to perform the DNase test for biotyping enteric campylobacters. PMID- 1855825 TI - Murine pathogenicity of Trichomonas vaginalis & its susceptibility to metronidazole. AB - Eight isolates of T. vaginalis obtained from clinical specimens were tested for their pathogenicity in the murine model using the subcutaneous route of inoculation. In general, all isolates produced localised purulent abscesses in the mice. On comparison with a reference strain, all but two isolates were found to be significantly more pathogenic for mice than the reference strain, while two were comparable in their pathogenicity. All eight isolates were sensitive in vivo to metronidazole. In six of the eight isolates, metronidazole (30 mg/kg body wt) administered for four days to subcutaneously infected mice effected a 100 per cent cure. The ED50 values ranged from 3.4 to 23.94 mg/kg body weight. None of the isolates could be termed as resistant. PMID- 1855826 TI - Microbiological evaluation of female patients in STD clinics. AB - A total of 215 women patients attending the STD clinic were evaluated in an attempt to isolate the different microorganisms in sexually transmitted diseases (STD). Mycoplasmas (30.22%), Candida species (20.00%), Trichomonas vaginalis (wet mount study; 15.81%), beta haemolytic streptococci (13.48%), Neisseria gonorrhoeae (9.30%), Staphylococcus aureus (13.95%), inclusion bodies of Chlamydia trachomatis (11.60%) and Gram negative organisms (9.30%) were isolated from these patients. Sera of all patients screened for HBsAg by ELISA showed a carrier rate of 12.5 per cent; 29.8 per cent sera were reactive in the VDRL test at the dilutions varying from 1:4 to 1:64. PMID- 1855827 TI - Rapid identification of clinically important bacteroides by coagglutination method. AB - A coagglutination technique using indigenous reagents was applied for the rapid identification of Bacteroides fragilis and the black pigmented bacteroides group, using colony suspensions. All the 58 strains of B. fragilis and 42 strains of black pigmented bacteroides tested could be correctly identified by this method. The specificity of the coagglutination reagent was confirmed by the absence of cross reactivity with the related species of bacteroides, viz., B. distasonis, B. ovatus, B. vulgatus and B. thetaiotaomicron as well as other anaerobic and aerobic bacteria. A panel of four antisera against B. fragilis was required for correct identification of the strains tested, indicating the presence of multiple serotypes. On the other hand, all 42 strains of black pigmented bacteroides tested could be identified, using a single reagent as these strains appeared to have no antigenic type variants. PMID- 1855828 TI - N-nitroso compounds and human cancer: where do we stand? AB - Humans are exposed not only to preformed N-nitroso compounds (NOC) but also to a wide range of nitrogen-containing compounds and nitrosating agents which can react in vivo to form NOC, a versatile class of carcinogens. Nitrosating agents and NOC can also be synthesized endogenously in reactions mediated by bacteria and activated macrophages. Thus, endogenous formation of NOC can occur at various sites in the body. A sensitive procedure (the N-nitrosoproline (NPRO) test) has been developed to estimate exposure of humans to exogenous and endogenous NOC. Results of studies in human subjects with this test led to the following conclusions: (1) The process of endogenous nitrosation in humans is influenced by many factors; therefore, determination only of nitrate and nitrite in body fluids is insufficient to assess the extent of nitrosation in man in vivo. (2) In clinical studies to examine the model of gastric carcinogenesis based on bacterial colonization and nitrosation in vivo, progress has been made in explaining some steps, but several controversies remain. Although bacterial strains possessing enzymes that catalyse N-nitrosamine formation at neutrality have been isolated from the gastric juice of achlorhydric subjects, their precise role in gastric carcinogenesis remains to be clarified. (3) Formation of endogenous NOC was assessed by the NPRO test in: (i) subjects living in high- and low-incidence areas for stomach cancer in northern Japan, Costa Rica and Poland; (ii) subjects with different habits of betel-quid chewing and tobacco use; (iii) patients with urinary bladder infections; and (iv) subjects infested with liver fluke in Thailand. In all instances, greater exposure to endogenous NOC was found in high-risk subjects, but individual exposure was greatly affected by dietary modifiers of disease state: ascorbic acid efficiently lowered the body burden of intragastrically formed NOC. (4) Increased nitrosation is also observed in tobacco smokers, adding to the body burden of ingested or inhaled tobacco-related carcinogens. These results, together with the knowledge that NOC produce tumours in 40 animal species, clearly underline the potential role of NOC (and other nitrite-reactive compounds) in human cancer etiology, particularly when exposure starts early in life and persists over a long period. The demonstrated efficacy of certain vitamins as nitrosation inhibitors also provides a plausible interpretation of epidemiological findings that have shown protective effects of fruits and vegetables (sources of vitamins and polyphenols) against various malignancies and particularly stomach cancer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1855829 TI - Tenth international meeting on N-nitroso compounds, mycotoxins and tobacco smoke: relevance to human cancer. PMID- 1855830 TI - A rapid gas chromatography-mass spectrometry method for the determination of urinary 3-methyladenine: application in human subjects. AB - A rapid gas chromatography-mass spectrometry method, employing immunoaffinity clean-up, has been developed for the measurement of 3-methyladenine in human urine samples. A wide variation in levels of urinary 3-methyladenine was observed, indicating that at least some may be derived from the diet and not be related to endogenous nitrosation and subsequent methylation. PMID- 1855831 TI - Tandem mass spectrometric approaches for determining exposure to alkylating agents. AB - Tandem mass spectrometric techniques have been developed for analysing alkylated purines in human urine. These techniques are designed with the objectives firstly of identifying unknown adducts derived from mixed exposures to alkylating agents, and secondly of quantifying these adducts with minimal sample purification. PMID- 1855832 TI - Relevance of N-nitrosamines to oesophageal cancer in China. AB - Oesophageal cancer occurs at a very high frequency in certain areas of China, especially in Linxian county, Henan province. Previous studies suggested that N nitroso compounds play a causative role. In order to study further the exposure of Linxian inhabitants, the intake of N-nitrosamines in the diet was determined. The total daily intake of volatile nitrosamines and of N-nitroso-N methylbenzylamine (NMBzA) was higher in Linxian than in two other counties. NMBzA can induce cancer in animal and human oesophageal epithelium. Human fetal oesophageal epithelia were cultured with NMBzA for 4 h, and eight monkeys were treated with NMBzA. High-molecular-weight DNA extracted from explants and from the oesophageal epithelia of monkeys induced malignant transformation of NIH 3T3 cells. Alu and monkey-specific repeat sequences were present in transformed cells, and H-ras was found in the transforming DNA. Human fetal oesophageal epithelium cultured with NMBzA was transplanted into the mesentery of BALB/c nude mice. Tumours were found after eight months; and the Alu sequence was present in DNA extracted from tumours induced by NMBzA, showing that the tumours were of human origin. The results provide direct evidence that NMBzA is carcinogenic in human oesophageal epithelium and that N-nitrosamines are one of the causative factors of oesophageal cancer in Linxian county. PMID- 1855834 TI - Promutagenic lesions persist in the DNA of target cells for nitrosamine-induced carcinogenesis. AB - Immunohistochemical procedures for the location of O6-methylguanine (O6-meGua) permit detection of cells proficient for the metabolism of N-nitrosodimethylamine (NDMA) and deficient for the repair of this DNA lesion. Such cells are potentially at high risk for cancer induction and are present in various tissues. In animals maintained on a protein-deficient diet, the distribution and intensity of alkylation of individual cells is altered, particularly in liver where fewer cells apparently retain the capacity to metabolize the nitrosamine, thereby permitting increased levels of alkylation in other tissues. In the renal cortex, specific, O6-meGua-positive target cells for renal cancer induced by a single dose of NDMA in weanling rats persist at least up to the appearance of early lesions. Persistence of alkylated cells in several tissues indicates prospects for the detection of environmental exposure. PMID- 1855833 TI - Quantification of 4-hydroxy-1-(3-pyridyl)-1-butanone released from human haemoglobin as a dosimeter for exposure to tobacco-specific nitrosamines. AB - A method was developed to quantify globin adducts of the tobacco-specific nitrosamines 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) and N' nitrosonornicotine (NNN). Globin adducts of NNK and NNN release 4-hydroxy-1-(3 pyridyl)-1-butanone (HPB) after mild treatment with a base. HPB was analysed as its pentafluorobenzoate by capillary column gas chromatography with detection by negative-ion chemical ionization-mass spectrometry and selected-ion monitoring. The detection limit for HPB-pentafluorobenzoate was approximately 1 fmol/injection. The method was applied to haemoglobin from snuff dippers, smokers and nonsmokers. Adduct levels were highest in snuff dippers (517 +/- 538 fmol HPB per gram haemoglobin), followed by smokers (79 +/- 189 fmol HPB per gram haemoglobin) and nonsmokers (29.3 +/- 25.9 fmol HPB per gram haemoglobin). The method will be useful in assessing the role of tobacco-specific nitrosamines as causes of cancer in smokers and snuff dippers. PMID- 1855835 TI - Nitrite-trapping capacity of thioproline in the human body. AB - Human nitrosating capacity has been monitored using proline; however, N nitrosothiazolidine 4-carboxylic acid (NTCA; N-nitrosothioproline), one of the predominant N-nitroso compounds in human urine, is also nonmutagenic and, presumably, noncarcinogenic. Thioproline is nitrosated about 1000 times faster than proline in vitro, and NTCA is excreted into the urine without being metabolized. We have therefore proposed thioproline as an effective nitrite trapping agent in the human body. Recently, we found thioproline in various cooked foods, including cod and dried shiitake mushrooms. In the study reported here, we evaluate the nitrite trapping capacity of thioproline in a male nonsmoking volunteer ingesting NO3- and eating a controlled diet. The highest level of NTCA excreted, 5.89 mumol, was measured after the subject ingested 6 mmol NO3- followed by 0.45 mmol (60 mg) thioproline. We estimated the effective amount of nitrite, defined as the actual amount of nitrite participating in nitrosation in the stomach, to be 0.3% of the NO3- ingested. Thus, the effective amount of NO2- for 6 mmol NO3- ingested was calculated to be 18 mumol, and 33% of this nitrite was trapped by ingestion of 0.45 mmol thioproline. We conclude that thioproline is a most sensitive probe for evaluating human nitrosating capacity and an effective nitrite-trapping agent. PMID- 1855837 TI - Effect of ascorbic acid on the intragastric environment in patients at increased risk of developing gastric cancer. AB - Ascorbic acid has been shown to decrease nitrosation in vivo, and epidemiological data suggest that the consumption of foods rich in this vitamin is associated with a reduced risk for gastric cancer. In order to study this suggestion further, fasting gastric juice samples were obtained from 62 high-risk patients (seven with atrophic gastritis, ten with pernicious anaemia, ten with partial gastrectomy, 21 with vagotomy and drainage and 14 with highly selective vagotomy), before, during four weeks' treatment with 1 g ascorbic acid four times daily, and four weeks after treatment. Samples were analysed for pH, total and nitrate-reducing bacterial counts, nitrite and N-nitroso compounds. Treatment with ascorbic acid lowered the median pH only in the vagotomized patients (p less than 0.001) but resulted in a reduction in median nitrate-reducing bacterial counts and in nitrite and N-nitroso compound concentrations in all groups, except for an increase in the nitrate-reducing bacterial count in atrophic gastritis patients and in nitrite in those with pernicious anaemia. These data suggest that treatment with a high dose of ascorbic acid reduces the intragastric formation of nitrite and N-nitroso compounds. PMID- 1855836 TI - Endogenous N-nitrosation and cancer of the biliary tract. AB - Evidence is presented that N-nitroso compounds occur in bile from patients who have undergone surgery for gallstones or had gastrectomy and from unoperated persons. It is unlikely, therefore, that local formation of nitrosamines can account for the excess risk for gallbladder cancer in the first two groups. Gastric formation remains the likeliest hypothesis. PMID- 1855838 TI - An approach to establishing N-nitroso compounds as the cause of gastric cancer. AB - Although gastric cancer is the most common cause of mortality from cancer, its etiology is not yet clear. To elucidate the role of N-nitroso compounds, we investigated 30 cases of gastric cancer by determination of the contents of nitrate and ascorbic acid and by detection of mutagens in urine. Cases were paired 1:1 with patients with dysplasia and normal controls of the same sex and age group. In comparison with normal controls, the gastric cancer group had higher nitrate and lower ascorbic acid levels in urine. Mutagenicity was observed in the urines of 83.3% of the gastric cancer cases and in 16.6% of the dysplasia group, but in none of those from normal controls. When the N-nitroso compound content of gastric juice was determined, the levels in control subjects were significantly lower than those in persons with gastric cancer. These results support the hypothesis that the cause of gastric cancer may be N-nitroso compounds. PMID- 1855839 TI - The N-nitrosoproline test as a measure of cancer risk in geographical comparison studies: results from Italy and an overall comparison. AB - The N-nitrosoproline (NPRO) test has been used in studies in which populations at high risk of cancer have been compared with equivalent populations at lower risk, to examine whether the geographical variation in cancer risk correlates with propensity for endogenous nitrosation, as assessed by the NPRO test. The usual method employed has been to determine NPRO in 12- or 24-h urine samples, after ingestion of L-proline, in a representative sample of the general population. We present results from one such geographical study conducted in two regions of Italy (Florence and Cagliari) with an approximately three-fold variation in gastric cancer mortality. The nonsignificant difference in mean NPRO excretion between the two populations was insufficient to explain the difference in cancer risk. The fact that there are appreciable international differences in formation of NPRO suggests, firstly, that nitrosation may be of relevance to cancer risk in some countries but not in others and, secondly, that variations within one country may not be large enough for significant geographical differences to be evident. Multivariate analysis of individual, rather than grouped, results from our Italian study made it possible to quantify the relevance of different factors to NPRO formation: a major factor is exposure to nitrate. Important relationships may be missed by analysing only grouped data. PMID- 1855840 TI - Role of nitrosamides in the high risk for gastric cancer in China. AB - Gastric cancer is the leading cause of death from cancer in China. Samples of fish sauce, a traditional seasoning, were collected in the high-risk area for gastric cancer in the Fuzhou area, Fujian Province. When fish sauce samples were nitrosated at pH 2.0, direct mutagenicity and high contents of N-nitrosamide were detected (30.9-78.0 microM); the N-nitrosamide content of three samples of fish sauce made in Guangdong and purchased from a market outside Fujian were low (2.1 6.0 microns). When the nitrosated fish sauce extract was given to newborn rats by gavage, dysplasia and adenocarcinoma were induced in the glandular stomach in the 4th and 16th experimental week, respectively. N-Nitrosamides were also found in fasting gastric juice from patients with chronic gastritis in the high-risk area of Putian. The mean concentration of total N-nitrosamides in the extracts correlated with the severity of gastritis in the stomach. These findings indicate that N-nitrosamides may play an important role in causing gastric cancer in China. PMID- 1855841 TI - Microflora of the nasopharynx in Caucasian and Maghrebian subjects with and without nasopharyngeal carcinoma. AB - The possible role of bacteria in the etiology of nasopharyngeal carcinoma (NPC) was studied by bacteriological and biochemical analyses of nasopharyngeal swabs collected in the cavum and in the fossa of Rosenmuller of NPC patients and healthy controls in France and Algeria. Counts of total bacteria and of total nitrate-reducing bacteria, mainly enterobacteria, were higher in the Maghrebians than in the Caucasians. The composition of the bacterial flora was different: in Maghrebians, enterobacteria were present in five of 17 control subjects and eight of 15 NPC patients, while the prevalence was only one out of 15 control subjects in Caucasians. Twelve of 32 bacterial species isolated from Caucasians and Maghrebians with normal or tumorous nasopharyngeal microflora were able to catalyse nitrosation of morpholine in vitro. This result suggests that colonization of the nasopharynx by microflora that contain nitrate-reducing microorganisms which can form N-nitroso compounds might represent a risk factor for NPC in Maghrebian populations. PMID- 1855842 TI - Exposure to N-nitrosamines and other risk factors for gastric cancer in Costa Rican children. AB - The hypothesis that endogenous chemical nitrosation in the normal stomach in early life could play a crucial role in inducing chronic atrophic gastritis/intestinal metaplasia in later life was tested by applying the N nitrosoproline (NPRO) test to 12-h urine samples from about 50 children (aged 8 14 years) living in high- and low-risk areas for stomach cancer. The median values of NPRO and the sum of four nitrosamino acids analysed were 0.28-0.84 micrograms/12 h and 0.75-1.75 micrograms/12 h, respectively. The NPRO level after proline intake was significantly higher in children from a high-risk area than in those from a low-risk area (p less than 0.04), and markedly reduced after ingestion of ascorbic acid and proline (p less than 0.05). Urinary nitrate level was lower than that of adults. NPRO levels on the day of proline intake, however, correlated well with nitrate levels (p less than 0.001), indicating that children in a high-risk area in Costa Rica have high endogenous nitrosation potential. Blood samples were also collected from about 300 children (aged 7-20 years) and analysed for antibodies against Campylobacter pylori, a suspected gastritis causing bacteria. About 71% of children in both high- and low-risk areas for stomach cancer had antibodies. In addition, raw and cooked beans, which are consumed very frequently in Costa Rica, were collected from families in both areas and analysed for levels of nitrite/nitrate, total N-nitroso compounds and genotoxicity in the SOS chromotest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855843 TI - Urinary excretion of N-nitrosoproline in relation to consumption of raw and cooked vegetables in a Danish rural population. AB - Several recent case-control studies of gastric cancer have demonstrated the protective effect of consumption of vegetables. According to Correa's model of gastric carcinogenesis, the initiating agent is N-nitroso compounds either ingested or formed in vivo. In our study of endogenous nitrosation, we measured intragastric formation of N-nitroso compounds in 285 individuals by the nitrosation of proline; in this presentation we analysed the effect of consumption of vegetables on urinary excretion of N-nitrosoproline (NPRO). When adjustment was made for the dominating determinants of NPRO excretion (total nitrate intake and tobacco smoking), a marked difference in the effects of consumption of raw and cooled vegetables was seen: consumption of cooked vegetables increased endogenous nitrosation of proline, while consumption of raw vegetables had only a marginal effect. We suggest that the difference between raw and cooked vegetables is due to destruction of ascorbate in the cooking of the vegetables. The lack of a protective effect of consumption of raw vegetables on the rate on endogenous nitrosation of proline indicates, however, that the determinants of nitrosation of proline and the determinants of gastric cancer risk may be different. PMID- 1855844 TI - N-nitroso compounds, genotoxins and their precursors in gastric juice from humans with and without precancerous lesions of the stomach. AB - We are investigating the interrelationships between levels of total N-nitroso compounds (NOC), genotoxic activity (both before and after nitrosation), degree of bacterial colonization in gastric juice and degree of severity or absence of precancerous lesions of the stomach. The mean level of constitutive total NOC in gastric juice was similar in the different groups of patients, but it was higher in acidic gastric juice (n = 30) than in gastric juice at pH greater than 4.5 (n = 12). Acid-catalysed nitrosation of gastric juice in vitro increased the concentration of total NOC by up to several thousand fold, to a maximum of 1330 mumol/l. Genotoxicity, expressed as SOS-inducing potency per 100 microliters of gastric juice was measurable in only 20% of gastric juice samples tested. After acid-catalysed nitrosation, however, all samples showed genotoxic activity, the mean SOS-inducing potency being four to seven times greater than the corresponding constitutive value. There was no association between the mean SOS inducing potency of gastric juice and the severity of precancerous lesions. The mean SOS-inducing potency of neutral or basic gastric juice was slightly greater than that of acidic samples. In a kinetic study on N-nitrosation of gastric juice in vitro, a mixture of amino and amido substrates was nitrosated; both qualitative and quantitative individual differences in nitrosatable substrates in gastric juice were seen. Fractionation of acidic, neutral and basic nitrosated gastric juice samples revealed a preponderance of nonvolatile, unknown NOC with varying polarities. The results of our study suggest that only pH determines the nature and level of precursors of NOC and of nitrosation-dependent genotoxins in gastric juice. PMID- 1855845 TI - Urinary nitrate, nitrite and N-nitroso compounds in bladder cancer patients with schistosomiasis (bilharzia). AB - Urinary excretion of nitrite and of volatile and nonvolatile N-nitroso compounds is increased in schistosomiasis (bilharzia) patients with Schistosoma haematobium infection. This observation suggests that the formation of nitrite and N-nitroso compounds in vivo in the urinary bladder of bilharzial patients may be an important etiological factor in the induction of bladder cancer associated with S. haematobium infection. PMID- 1855846 TI - Dietary practices and cancer mortality in China. AB - An ecological survey on diet, life style and cancer mortality was carried out in 65 rural counties in China, using a questionnaire comprising 285 questions on environmental factors, dietary practices and other life style characteristics; in addition, blood, urine and food were collected and analysed. Two interpretations of preliminary data are presented. One is for the finding of a positive correlation between a latent variable, namely general nutritional status, and cancer mortality rates; the other is for a positive correlation between lipid peroxidation (plasma lipid peroxidase and copper) and oesophageal and gastric cancer mortality, and a negative correlation between dietary oxidants (plasma selenium, ascorbic acid and retinol) and mortality from oesophageal and gastric cancer. PMID- 1855847 TI - Formation of N-trimethyl-N-nitrosourea in the gastric lumen of the fistulated pig. AB - The formation of N-trimethyl-N-nitrosourea (TMNU) in the stomach of full-sized gastric-fistulated pigs was determined. Nitrite was added to the stomach in amounts that have been reported to occur in the human stomach (25-375 mumol). The vehicle was an 'artificial meal' made up of synthetic gastric juice. The total amount of TMNU formed (not concentration) was estimated by determining the concentration and gastric volume using multiple additions of a nonabsorbable marker (polyethylene glycol). At an initial pH of 3, 23-1000 micrograms of TMNU were found after 10-25 min. The rate of loss of polyethylene glycol and TMNU from the stomach were the same, indicating that TMNU was not directly absorbed. These data suggest that formation of TMNU under conditions similar to those found in the human stomach is possible. PMID- 1855848 TI - Bacterial formation of N-nitroso compounds in the rat stomach after omeprazole induced achlorhydria. AB - N-Nitrosamine formation by bacteria in the achlorhydric stomach has been proposed as an important factor in the development of gastric cancer. Thus, the effect of the presence of bacteria in the stomach on endogenous nitrosation was investigated in rats given omeprazole (an inhibitor of gastric H+, K((+)-ATPase) which reduces gastric secretion sufficiently to allow survival of a bacterial suspension of Escherichia coli or Pseudomonas. When rats were given both thiazolidine 4-carboxylic acid and nitrate, greater endogenous nitrosamine formation was observed in rats receiving omeprazole and an E. coli suspension than in control or omeprazole-treated rats. A similar result was obtained when rats were given morpholine and nitrate. Since the endogenous formation of N nitrosomorpholine (NMOR) can be evaluated more precisely from the levels of its urinary metabolites, N-nitrosohydroxyethylglycine (NHEG), the metabolism of NMOR was studied in omeprazole-treated rats. In this preliminary study, we showed that 60% of an oral dose of NMOR was excreted as NHEG, while in rats with a higher gastric pH 20% was excreted as NHEG. The amount of endogenously formed NMOR was increased in omeprazole-treated rats given morpholine and nitrite together with bacteria, and greater excretion of unchanged urinary NMOR was observed. Thus, as shown in this in-vivo model, bacteria efficiently reduce nitrate to nitrite and catalyse nitrosation, resulting in increased endogenous formation of N-nitroso compounds in the achlorhydric stomach. PMID- 1855849 TI - Epidemiological study of precursor lesions of oesophageal cancer among young persons in Huixian, China. AB - A total of 538 subjects (354 males, 184 females) were investigated in a high-risk area for oesophageal cancer in China to provide large-scale data on the prevalence of chronic oesophagitis among persons below 25 years of age. The survey included an oesophagoscopy with guided biopsies and cytology, a physical examination, an interview and collection of a 10-ml blood sample and overnight urine. Histologically confirmed oesophagitis was found in 43.5% of male and 35.6% of female subjects. Mild and moderate oesophagitis was associated positively with consumption of burning hot beverages, family history of oesophageal cancer, frequent consumption of cottonseed oil, cigarette smoking, a clinical diagnosis of oral leukoplakia and seborrhoeic dermatitis; negative associations were seen with frequent consumption of fresh fruit, meat and eggs. A significantly higher level of urinary nitrate was found in the diseased group, but no difference was seen with regard to any of the N-nitrosamino acids measured. PMID- 1855850 TI - Gliomas and meningiomas in men in Los Angeles County: investigation of exposures to N-nitroso compounds. AB - We conducted a case-control study of primary tumours of the brain and cranial meninges in Los Angeles County to investigate the hypothesis that these tumours are related to occupational exposures. We also collected limited data on diet and personal habits that are likely to involve exposure to N-nitroso compounds (NOC), NOC precursors and modulators of NOC metabolism. Interviews were conducted with 272 men with a brain tumour diagnosed in 1980-84 and with 272 individually matched neighbourhood controls. The study was of sufficient size to allow for separate analyses of the 202 pairs of glioma patients and of the 70 patients of meningioma. Six glioma cases and one control had worked in the rubber industry, in which excesses of brain tumour have been shown in previous studies and where there are high levels of volatile NOC at various work sites. Ten meningioma patients and five controls had used cooling, cutting or lubricating oils, and most had used these daily (eight cases; four controls). Cases and controls were not different, however, with respect to other occupations known to involve exposures to NOC. Cases and controls also did not differ in their consumption of alcoholic beverages or cigarettes or in their passive exposure to cigarette smoke. The most striking dietary finding was a significant protective effect among glioma pairs of use of vitamin supplements, which increased with increasing frequency of use (p for trend = 0.04; odds ratio for use at least twice a day = 0.4 (95% confidence interval = 0.24-0.77)).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855851 TI - Dietary sources of N-nitrosamines in a high-risk area for oesophageal cancer- Kashmir, India. AB - Samples of foods consumed frequently in Kashmir, a high-risk area for oesophageal cancer, were analysed for the presence of volatile N-nitrosamines. Relatively high levels of N-nitrosodimethylamine (NDMA), N-nitrosopiperidine (NPIP) and N nitrosopyrrolidine (NPYR) were detected in smoked fish (20 micrograms/kg NDMA), sun-dried spinach (5.8 micrograms/kg NDMA; 23.8 micrograms/kg NPIP), sun-dried pumpkin (24.6 micrograms/kg NPYR) and dried, mixed vegetables (10 micrograms/kg NDMA). The possible role of N-nitrosamines in the etiology of oesophageal cancer in Kashmir is discussed. PMID- 1855852 TI - Volatile N-nitrosamines in fish meal, with special reference to the mechanism of formation of N-nitrosothiazolidine. AB - Volatile N-nitrosamines in 32 commercial Japanese fish meal samples were analysed, and three compounds, N-nitrosodimethylamine, N-nitrosopyrrolidine and N nitrosothiazolidine (NT), were detected. We also examined the mechanism of formation of NT during fish meal production. Both cysteamine and thiazolidine were found to be precursors of NT. The cysteamine content decreased during boiling and drying of the fish; but that of thiazolidine increased during boiling. N-Nitrosothiazolidine 4-carboxylic acid (NTCA) was formed in sardine meal after treatment with nitrogen dioxide gas, and the rate of formation of NT from NTCA added to sardine meal was as high as 10% when the meal was heated at 160 degrees C for 60 min. We propose two pathways for NT formation during fish meal manufacture: (1) cysteamine----thiazolidine----NT; and (2) cysteine--- (thiazolidine 4-carboxylic acid)----NTCA----NT. PMID- 1855853 TI - Regional differences in N-nitrosamine content of traditional Chinese foods. AB - Traditional uncooked and cooked Chinese foods from six provinces with different cancer patterns were analysed for volatile N-nitrosamines (VNA) by gas chromatography-thermal energy analysis. Selected samples were also analysed for N nitrosamino acids (NAA). N-Nitrosodiethylamine was the VNA found most often (in 91/108 samples; less than 0.2-17.5 micrograms/kg), followed by N nitrosodimethylamine (in 75/108 samples; less than 0.2-17.3 micrograms/kg). N Nitrosodipropylamine was detected in 11/108 samples (0.9-6.2 micrograms/g). Samples selected for analysis of NAA on the basis of their VNA content contained one or more NAA, including N-nitrosoproline and N-nitrosothiazolidine 4 carboxylic acid (range, 1.1-115 micrograms/kg; average, 35 micrograms/kg). Both the incidence and pattern of occurrence of VNA suggest that Chinese foods differ from western foods, which would not be expected to contain NAA as frequently nor to contain N-nitrosodipropylamine. The highest percentages of positive samples were from Zhejiang and Fujian provinces (89 and 91%, respectively), and they had the highest average VNA content. Beijing city and Sichuan province gave the lowest percentages of positive samples (75 and 56%, respectively) and the lowest average VNA content. PMID- 1855854 TI - The etiology of gastric cancer. AB - We review recent evidence concerning risk factors for gastric cancer. An overview of analytical studies shows convincing evidence of a protective effect of fruit and vegetables. The specific protective constituents have not been firmly established, but micronutrients, especially ascorbic acid, are probably of importance. Other dietary factors that show a consistent pattern of effect in different studies are the moderate risks associated with high intake of preserved foods and salt. Evidence also indicates that gastric cancer is associated with tobacco consumption, although even in continuing heavy smokers the risk does not exceed two fold. Another non-dietary factor of potential importance is infection with the bacterium, Helicobacter (Campylobacter) pylori. The model of Correa and co-workers currently offers the best working hypothesis to explain the etiology of gastric cancer. Although the endogenous synthesis of N-nitroso compounds is central to the model, it is not yet clear what the rate-limiting steps are. Exposure to nitrate per se does not directly cause gastric cancer. PMID- 1855855 TI - Trace analysis of N-nitrosoureas by their alkylating activity. AB - N-Nitrosoureas can be analysed indirectly by gas chromatography with chemoluminescence detection after reaction of the corresponding diazoalkanes with the scavenger reagent N-nitroso-N-tert-butylglycine. A lower determination limit of 2 ng N-methyl-N-nitrosourea per sample is achieved. The method is specific for N-nitroso compounds, which release nonpolar diazoalkanes upon alkaline treatment. PMID- 1855856 TI - Potential occupational exposure associated with parenteral administration of N nitrosodiethylamine to Macaca mulatta: evidence of post-injection release to the atmosphere. AB - In order to assess the exposure of workers administering N-nitrosodiethylamine (NDEA) parenterally to Macaca mulatta, air samples were drawn through Thermosorb/N cartridges. Samples were analysed by gas chromatography-thermal energy analysis; the limit of detection was 0.02 micrograms/m3. Significant amounts of NDEA were found in those samples taken in the animal holding room. The NDEA recovered may be accounted for by its expiration by the animals (the contribution from excreta and leakage from the injection site is probably minor). On the basis of the total amount of NDEA administered (840 mg during the first experiment and 250 mg in the second) and the rate at which the animal holding room was ventilated, and assuming that the samples were representative, we estimate that 0.9% of the NDEA administered was released to the atmosphere in 5 h in the first experiment and that 2.7% and 0.8% were released in the first and second 24-h periods, respectively, in the second experiment. It should be noted that this potential source of exposure may be significant not only for workers but also for control or other experimental animals housed in the same room. PMID- 1855857 TI - Analysis of volatile N-nitrosamines in beer and food in China. AB - Capillary gas chromatography-thermal energy analysis was used for the study of volatile N-nitrosamines in comestibles. The finding of a comparatively high content of N-nitrosodimethylamine in some Chinese beers confirms the results of other authors. We describe studies of Chinese foods and environmental samples carried out in this laboratory in collaboration with epidemiological groups. The concentrations of N-nitrosamines could be correlated with mortality from digestive cancer. PMID- 1855858 TI - Recent studies in Canada on the occurrence and formation of N-nitroso compounds in foods and food contact materials. AB - We present data on the levels of both volatile and nonvolatile N-nitroso compounds in various smoked meats, including bacon, and in food contact materials (e.g., baby bottle rubber nipples and pacifiers). Evidence presented suggests that the formation of N-nitrosothiazolidine and N-nitrosothiazolidine 4 carboxylic acid in smoked meats and bacon and that of N-nitroso-N-methylaniline in Icelandic smoked mutton, can be minimized by changing or modifying the smoking methods. The presence of two other nonvolatile N-nitroso compounds in these products is also reported. PMID- 1855859 TI - Occurrence of and exposure to N-nitrosamines in Sweden: a review. AB - During the last ten years, over 900 samples of foods, snuff and other products on the Swedish market were analysed for N-nitrosamines. The average daily intake of volatile N-nitrosamines from foods was estimated to be 0.29 micrograms/person, and the daily intake of tobacco-specific N-nitrosamines from snuff was calculated to be up to 110 micrograms/snuff user. PMID- 1855860 TI - N-nitrosoalkanolamines in cosmetics. AB - A method has been developed for the determination of the N-nitrosoalkanolamines, N-nitrosodiethanolamine (NDELA) and N-nitrosobis(2-hydroxypropyl)amine (NDHPA) in cosmetics. In model systems, we studied nitrosation of the most relevant precursors by NaNO2, by the preservatives Bronopol and Bronidox and by nitric oxides. Secondary amines were most rapidly nitrosated, and Bronopol, Bronidox and atmospheric nitric oxides appeared to be the most relevant nitrosating agents. In order to remove the most important sources of contamination, the Federal Health Office issued an official recommendation to producers to avoid use of secondary amines in cosmetics (March, 1987). Analysis of cosmetics taken from the German market 6-18 months later showed that only 19/126 samples were contaminated with NDELA (12-235 micrograms/kg or NDHPA (40-215 micrograms/kg). The results reflect a strong downward trend in contamination. PMID- 1855861 TI - N-nitrosodimethylamine content of US and Canadian beers. AB - A total of 194 beers (148 US and 46 Canadian) were analysed for volatile N nitrosamines. The sampling was designed to include different types of beers brewed from malts at all commercial-scale malt houses by the major beer manufacturers in both countries. N-Nitrosodimethylamine (NDMA), the only volatile N-nitrosamine detected, was found in 56% of the beers (detection level, 0.05 microgram/kg), at a mean level of 0.074 microgram/kg. The results indicate that NMDA levels in present-day US and Canadian beers are approximately 1-5% of what they were a decade ago. PMID- 1855862 TI - Nitrosation of tertiary aromatic amines related to sunscreen ingredients. AB - Possible routes to the formation of the sunscreen contaminant, 2-ethylhexyl 4-N methyl-N-nitrosoaminobenzoate, have been investigated in a study of the nitrosation chemistry of 2-ethylhexyl 4-N,N-dimethylaminobenzoate (Padimate-O) and related tertiary and secondary amines. Padimate-O and the corresponding ethyl ester nitrosate rapidly at 25 degrees C in either N2O3:ether or HNO2:HOAc to produce a mixture of alkyl 4-N-methyl-N-nitrosoaminobenzoate and alkyl 4-N,N dimethylamino-3-nitrobenzoate, the former of which is the major product. The nitrosative dealkylation of these amines at this low temperature is unusual. Asymmetrical amines exhibit a preference for nitrosative demethylation (methyl versus ethyl or benzyl), but the cleavage ratios in N2O3:ether are time dependent, suggesting competing mechanisms with different reactant kinetic orders. A radical cation route would explain the unusual reactivity, which may compete with the established nitrosative dealkylation mechanism. 2-Ethylhexyl 4-N methyl-N-nitrosoaminobenzoate was mutagenic in two strains of Salmonella typhimurium in the Ames assay. PMID- 1855863 TI - Mutagenicity of Alternaria alternata and Penicillium cyclopium isolated from grains in an area of high incidence of oesophageal cancer--Linxian, China. AB - In order to study the relationship between daily consumption of mouldy food and the incidence of oesophageal cancer, we examined the mutagenicity of Alternaria alternata and Penicillium cyclopium, which seriously contaminate grain in Linxian county, China. We first examined extracts of cultured strains of A. alternata. In the reverse mutation test, positive results were obtained in 85% of strains; positive results were seen in 84% of 19/20 strains in the rec assay. Eight of ten strains induced sister chromatid exchange, and two of eight strains induced chromatid breaks. Six of seven strains induced unscheduled DNA synthesis and DNA synthesis inhibition. One extract induced a higher frequency of sister chromatid exchange in lymphocytes from normal persons than in those from patients with oesophageal cancer, and the spontaneous break-points in patients were related to fragile sites and neoplasia-associated break-points. The toxins alternariol and its monomethyl ether, produced by A. alternata, were examined in the reverse mutation assay and for unscheduled DNA synthesis. The results were similar to those obtained with extracts of the different strains. Alternariol had a four to eight times greater effect than its monomethyl ether. Of 24 strains of P. cyclopium isolated from cereals in Linxian, four were cultured with rice and 19 in Raulin-Thom medium. Cultures in Raulin-Thorn medium, solution and hyphae were then extracted. The strains cultured with rice induced sister chromatid exchange, unscheduled DNA synthesis and DNA synthesis inhibition. The solution extracts of 14 strains were positive in the rec assay, and five strains were positive in the reverse mutation test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855864 TI - Relationships between Alternaria alternata and oesophageal cancer. AB - Although it is uncertain whether fungi can produce the mycotoxins that induce oesophageal cancer, the tumorigenicity of fungi isolated from grain in an area of high incidence of oesophageal cancer has been confirmed. Alternaria alternata is a fungus of importance in this respect. The contamination rate with A. alternata in corn from areas of high morbidity from oesophageal cancer is higher than that in low-morbidity areas. Extracts of A. alternata induced reverse mutation in Escherichia coli, unscheduled DNA synthesis in cultured human amnion FL cells, chromosomal aberrations and sister chromatid exchange in human peripheral blood lymphocytes, mutation in V79 cells and transformation of NIH3T3 cells. Alternariol methyl ether, which is an active compound produced by this fungus, also induced transformation of NIH3T3 cells, and the transformed cells grew in soft agar and were tumorigenic in nude mice. Food mildewed by this fungus induced forestomach tumours in rats. Thus, (i) A. alternata is tumorigenic, (ii) it has been isolated from corn in an area of high incidence of oesophageal cancer, and (iii) contamination with A. alternata in the area of high incidence is higher than that in the area of low incidence. We therefore believe that A. alternata is one of the causes of human oesophageal cancer. PMID- 1855865 TI - Enzyme mechanisms in the metabolism of nitrosamines. AB - Many nitrosamines are metabolized by cytochromes P450, one of which (P450IIE1) has received much attention because of its role in the metabolic activation of N nitrosodimethylamine. This enzyme exists in man, rat, mouse, hamster and other animal species. It is inducible by fasting, diabetes and exposure to ethanol, acetone, isoniazid, benzene and other chemicals. P450IIE1 is responsible for the low Km form of N-nitrosodimethylamine demethylase and is the major enzyme catalysing the metabolic activation of this carcinogen. In addition, P450IIE1 is the most active P450 species known in the metabolism of N-nitrosoethylmethylamine and N-nitrosopyrrolidine. In the metabolism of N-nitrosobutylmethylamine, P450IIE1 preferentially oxidizes the methyl group over the butyl group, whereas P450IIB1 efficiently oxidizes both the methyl and butyl groups. P450IIB1 also catalyses the alpha-oxygenation of both the pentyl and methyl groups of N nitrosopentylmethylamine, forming pentaldehyde and formaldehyde at a rate ratio of 2:1, as well as oxygenation at other carbons of the pentyl group. Many nitrosamines are effectively activated in nonhepatic target tissues. The metabolism of 4-(N-nitroso-methylamino)-1-(3-pyridyl)-1-butanone in lung and nasal microsomes is discussed. PMID- 1855866 TI - Areca-nut toxicity in cultured human buccal epithelial cells. AB - In cultured human buccal epithelial cells, at doses of 3-540 micrograms/ml, areca nut extract significantly decreased viability, as determined by colony-forming efficiency, clonal growth rate, ability to take up neutral red and ability to exclude trypan blue, and also caused significant formation of DNA single-strand breaks and DNA protein cross-links. Comparisons of the areca nut-related compounds, 3-(N-nitrosomethylamino)propion-aldehyde (NMPA), 3-(N nitrosomethylamino)propionitrile (NMPN), N-nitrosoguvacoline, N-nitrosoguvacine, arecoline, arecaidine, guvacoline and guvacine, in terms of the above endpoints, indicate that NMPA is ten times more cytopathic to buccal cells than the other agents on a molar basis. Because metabolism of NMPA can potentially yield several reactive breakdown products, including aldehydes, this study indicates that both the parent compound and its metabolites may contribute to the observed pathobiological effects. Taken together, the observed pathobiological effects of areca-nut extract and certain related compounds in cultured human buccal epithelial cells indicate that these agents may contribute to the oral carcinogenicity associated with chewing betel quid. PMID- 1855867 TI - Bioactivation of asymmetric N-dialkylnitrosamines in rat tissues derived from the ventral entoderm. AB - Aliphatic methylalkylnitrosamines with a chain length of three to six carbon atoms are powerful oesophageal carcinogens in rats and have been shown to methylate target organ DNA preferentially. This class of carcinogens is efficiently metabolized not only in the oesophageal mucosa but also in the mucosa of the nasal and oral cavity, trachea and bronchioli, i.e., tissues derived from the rat ventral entoderm. In order to determine whether more than one cytochrome P450 isozyme is involved in the bioactivation of asymmetrical aliphatic dialkylnitrosamines in these tissues, we have studied the effects of various modulators of nitrosamine metabolism, including dietary zinc deficiency, ethanol and disulfiram, on DNA alkylation by N-nitrosomethyl-n-butylamine (NMBA) and its ethyl analogue N-nitrosoethyl-n-butylamine (NEBA). Formation of O6-methyl- and O6 ethyldeoxyguanosine by a single dose of NMBA and NEBA, respectively, was quantified after a survival time of 6 h by immuno-slot-blot assay. In control rats, methylation of DNA by NMBA was highest in oesophagus, followed by nasal mucosa, liver and lung. Formation of O6-ethyldeoxyguanosine from NEBA, however, was twice as high in liver as in nasal mucosa and lung and four times as high in liver as in oesophagus. In oesophagus, trachea and bronchioli, both nitrosamines were selectively metabolized in mucosal cells. Bioactivation of NMBA and NEBA was almost completely inhibited in nasal mucosa by ethanol. In contrast, a striking interorgan shift in DNA methylation by NMBA from liver (-50%) to lung (+100%), oesophagus (+300%) and nasal mucosa (+400%) was obtained with dietary disulfiram, whereas only 20-50% increases in extrahepatic DNA ethylation were determined for NEBA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855868 TI - Role of oncogenes and tumour suppressor genes in human lung carcinogenesis. AB - Six families of activated protooncogenes, ras, raf, fur, neu, jun and myc have so far been associated with human lung cancer. Human bronchial epithelial cells in vitro are being used to investigate the functional role of these specific oncogenes and growth regulatory genes in carcinogenesis and tumour progression. When transferred into normal human bronchial epithelial cells by the highly efficient protoplast fusion method, the v-Ha-ras oncogene initiates a cascade of events leading to decreased responsiveness of these cells to inducers of squamous differentiation, aneuploidy and, less frequently, 'immortality' and tumorigenicity with metastasis in athymic nude mice. Transfection of the SV40 T antigen gene results in nontumorigenic cell lines that have a nearly normal pathway of terminal squamous differentiation and can be transformed into malignant cells by transfected Ha-ras, N-ras or Ki-ras. The combination of transfected c-myc and c-raf-1 also transforms human bronchial epithelial cells into neoplastic cells that exhibit some phenotypic traits found in small-cell carcinomas. These and other results indicate that proto-oncogenes dysregulate the pathways of growth and differentiation of human bronchial epithelial cells and play an important role in human carcinogenesis. Analyses of allelic deletion and somatic cell hybrids are being used to identify the chromosomal localization of tumour suppressor genes. We have examined 54 non-small-cell bronchogenic carcinomas with 13 polymorphic markers. Loss of heterozygosity was more frequent than among 23 squamous-cell carcinomas than among 23 adenocarcinomas or eight large-cell carcinomas. Loss of heterozygosity for chromosome 17p was found in 89% of cases of squamous-cell carcinoma and 18% of adenocarcinomas. Analysis of chromosome 11 for allelic deletions revealed two commonly deleted regions (11p13 and 11p15.5). Somatic cell hybrids between normal human bronchial epithelial cells and Hut292DM, a lung carcinoma cell line, had a finite lifespan in vitro and were nontumorigenic in athymic nude mice. Tumour suppressive effects of individual or combinations of specific human chromosomes on Hut292DM are being examined by formation of microcell-cell hybrids. Chromosome 11 has tumour suppressor activity in these hybrids. Both of these studies suggest that tumour suppressor genes play a dominant role in lung carcinogenesis and provide in-vitro model systems for isolating these genes by subtraction library and insertional mutagenesis techniques. PMID- 1855869 TI - Alkylation of DNA related to organ-specific carcinogenesis by N-nitroso compounds. AB - Alkylation of DNA by a number of methylating and ethylating carcinogens, mainly N nitroso compounds, has been examined in target and non-target organs of rats and Syrian hamsters. Six hours after administration by gavage of small doses identical to those given twice weekly for several months to elicit tumours, animals were killed and dissected. DNA was isolated from several organs and hydrolysed, and the content of methyl- and ethylguanines was measured using high performance liquid chromatography for separation. In most experiments, radiolabelled carcinogen was used, but in some cases measurement of alkylguanines was by fluorescence. Methylation, O6- and N7-, by methylating compounds was much more extensive than ethylation by the corresponding ethyl compounds, irrespective of their relative potencies in inducing tumours. Similar patterns of alkylation were found in target organs and in non-target organs of the carcinogens. Only marginal differences in methylation were seen with N-nitro-sobis(2 oxopropyl)amine between male and female rat livers, although liver tumours are induced only in females, in feminized males and in old males. Deuterium labelling of the methylene of N-nitrosoethylmethylamine had little effect on methylation or ethylation of DNA in rat liver, although the deuterated compound was a much more potent liver carcinogen. The conclusion is that reactions of the carcinogen other than alkylation of DNA are important in giving rise to tumours. PMID- 1855870 TI - Relationship between dose and risk reduction: statistical evaluation of a combination experiment with three hepatocarcinogenic N-nitrosamines in rats. AB - Data from an experiment on the single and combination effects of very low doses of N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR) and N nitrosodiethanolamine (NDELA) in 1800 male Sprague-Dawley rats were analysed for age-specific incidence (time to death with liver tumour) by Cox's proportional hazards model. The model revealed a linear relationship between daily exposure to low levels of N-nitrosamine and time to death with liver tumour within the dose range investigated: an increase in individual dose resulted in a proportional decrease in liver tumour-free survival. The finding was established for the three individual carcinogens as well as for their combination. NDEA was 40 times more active than NDELA. Extrapolation to N-nitrosamine exposure levels lower than those used in the experiment revealed only a minor reduction in age-specific liver tumour incidence compared to that achieved by an equivalent reduction within the experimental dose range. In rats at advanced age a further reduction in carcinogen-induced liver tumour incidence did not contribute to longer overall survival, due to competitive, probably independent causes of death. The data thus support the idea of a quasi-threshold in terms of a 'no observed effect level'. PMID- 1855871 TI - Carcinogenic activity of endogenously synthesized N-nitrosobis(2 hydroxypropyl)amine in rats. AB - The carcinogenic activity of endogenously synthesized N-nitroso-bis(2-hydroxy propyl)amine (NDHPA) was investigated in male Wistar rats administered bis(2 hydroxypropyl)amine (DHPA), mixed into a powdered diet at a concentration of 1%, and NaNO2 dissolved in distilled water at concentrations of 0.15% and 0.3%, for 94 weeks. Urinary excretion of NDHPA clearly demonstrated its endogenous synthesis in rats given 1% DHPA and 0.3% NaNO2, but not in the groups receiving either of these precursors alone. Tumours of the nasal cavity, lung, oesophagus, liver and urinary bladder were found in rats treated with 1% DHPA and 0.15% or 0.3% NaNO2. The incidences of nasal cavity and lung tumours reached 74% and 58% respectively, in rats given 1% DHPA and 0.3% NaNO2. The tumour distribution was almost the same as that seen in rats given NDHPA. These results indicate that endogenously synthesized NDHPA has similar carcinogenic activity to exogenously administered NDHPA in rats. PMID- 1855872 TI - Effects of long-term inhalation of N-nitrosodimethylamine in rats. AB - The toxicological evaluation and histopathological findings of a long-term inhalation study in progress with N-nitrosodimethylamine (NDMA) are presented. Exposure was to three concentrations of NDMA: 0.04, 0.2 and 1.0 ppm (corresponding to 120, 600 and 3000 micrograms/m3). A significant reduction in median survival time (nine months) was seen in animals treated with the highest concentration of NDMA. Tumours occurred mainly in the nasal cavity, with the highest incidences in the groups receiving 1.0 and 0.2 ppm NDMA (19/36 and 31/36 tumour-bearing animals); in the lowest exposure group, 13/36 nasal tumours have been observed. The survival time of this treatment group, however, was about two months longer than that of the controls. PMID- 1855873 TI - Specificity in the methylation of DNA by N-nitroso compounds. AB - A sequencing assay was used to determine the reactivity of N-nitroso compounds that are simple methylating agents with individual nucleotides in a defined DNA sequence. The maximal difference in reactivity between guanines is about five fold. DNA in the Z, cruciform and H conformations was shown to be methylated by N methyl-N-nitrosourea in a manner which was indistinguishable from the reactivity of B-DNA. Electronic factors rather than steric factors appear to dominate the methylation reaction. Transcriptionally active genes were shown to be methylated by N-nitroso compounds in vivo more extensively than untranscribed genes. The results suggest that local sequence, secondary conformation and transcriptional activity may all influence the carcinogenic potential of N-nitroso compounds. PMID- 1855874 TI - Etiological research on gastric cancer and its precursor lesions in Shandong, China. AB - Research over the past several years in an area of Shandong, China, with one of the world's highest rates of gastric cancer, has yielded clues to the environmental determinants of this tumour. Interviews with 564 gastric cancer patients and 1131 population-based controls revealed increased risks associated with consumption of sour pancakes, a fermented staple unique to the area, in samples of which volatile N-nitrosamines have been detected. Lower risks were found among people who had a higher intake of fresh vegetables, including garlic and other Allium vegetables which contain constituents that can inhibit carcinogenesis by N-nitrosamines and other substances in experimental animals. A pilot study involving assays of urine and gastric juice from 60 individuals in a screening programme showed higher levels of N-nitrosoproline and of cis- and trans-N-nitroso-2-methylthiazolidine 4-carboxylic acid among persons with gastric dysplasia than in either normal controls or those with chronic atrophic gastritis. We are trying to characterize the transition and progression of precursor lesions to gastric cancer and to evaluate the role of dietary variables, nutrients, N-nitroso compounds and other factors in particular stages of the carcinogenic process. PMID- 1855875 TI - Mechanism of action of the urinary bladder carcinogen N-nitrosobutyl-3 carboxypropylamine. AB - The carcinogenic action of N-nitrosodibutylamine in the urinary bladder is related to omega-oxidation of a butyl chain. N-Nitrosobutyl-4-hydroxybutylamine and its proximate metabolite N-nitrosobutyl-3-carboxypropylamine (NBCPA) selectively induce urinary bladder tumours in different animal species. The mechanism by which NBCPA exert its carcinogenic action is not known. We found a small but significant dealkylation of NBCPA with microsomes from rat liver or pig urinary bladder, which could be inhibited by SKF 525A. NBCPA was not mutagenic to Salmonella typhimurium (with or without external metabolizing systems from rat liver or pig urinary bladder) and did not induce DNA strand breaks in tumour cell lines (with or without external activation) or primary cells (rat hepatocytes, pig urinary bladder epithelia). Significant induction of sister chromatid exchange and micronuclei, however, was observed in human tumour cells. N Nitrosoureas that generate the same electrophiles as NBCPA after alpha- or via beta-oxidation (N-butyl-N-nitrosourea, N-3-carboxypropyl-N-nitrosourea and N-2 oxopropyl-N-nitrosourea) induced single-strand breaks in Namalva cells, the oxopropyl compound being more potent than the butyl or carboxypropyl compounds. Our data suggest that NBCPA is activated via alpha-oxidation in the urinary bladder, even though the activation rate in vitro is so low that a positive response is not detectable by classical short-term tests. Provided that beta oxidation to a highly genotoxic agent proceeds at an adequate rate, it might also be a relevant activation pathway. PMID- 1855876 TI - Mutagenicity, DNA damage and DNA adduct formation by N-nitroso-2 hydroxyalkylamine and corresponding aldehydes. AB - The potent carcinogen N-nitrosodiethanolamine (NDELA) becomes mutagenic to Salmonella typhimurium TA98 and TA100 when activated by alcohol dehydrogenase from yeast or horse liver. Metabolic pathways different from alpha-oxidation might therefore be important for the activation of N-nitroso-2-hydroxyalkylamines such as NDELA. In an in-vitro test system (Namalva cells), neither NDELA nor N nitrosoethyl-2-hydroxyethylamine was genotoxic, whereas the corresponding metabolites from alcohol dehydrogenase-mediated oxidation, N-nitroso-2 hydroxymorpholine and N-nitrosoethylethanalamine, induced single-strand breaks even at low doses. An immuno-slot-blot assay was used to study the formation of O6-2-hydroxyethyldeoxyguanosine in rat liver after oral administration of different N-nitroso-2-hydroxyalkylamines. When given at equimolar doses (0.375 mmol/kg), DNA hydroxyethylation was considerably lower (6.7 mumol/mol deoxyguanosine) with NDELA than with N-nitrosoethyl-2-hydroxyethylamine (48.7 mumol/mol deoxyguanosine) or N-nitrosomethyl-2-hydroxyethylamine (72.1 mumol/mol deoxyguanosine). N-Nitroso-2-hydroxymorpholine did not form detectable levels of O6-2-hydroxyethyldeoxyguanosine. PMID- 1855877 TI - N-Nitrosobutyl(4-hydroxybutyl)amine alpha-hydroxylation by rat liver and urothelial cell homogenates. AB - Determination of molecular nitrogen formed as a consequence of nitrosamine alpha hydroxylation provides a useful means for studying the extent of activation of these compounds in target and nontarget organs and tissues. alpha-Hydroxylation in rat liver and urothelial cells was compared using as substrate doubly 15N labelled N-nitrosobutyl(4-hydroxybutyl)amine (15N-NBHBA), a potent bladder carcinogen in rodents. Both enzyme sources metabolized 15N-NBHBA through the alpha-hydroxylation pathway. 15N2 production was dependent on the amount of substrate incubated. Vmax values for 15N2 production by urothelial cells and by liver postmitochondrial supernatant were 4.47 and 3.21 nmol/mg protein per h, respectively. PMID- 1855878 TI - Mechanism of DNA binding by the oesophageal carcinogen N-nitroso-N-methylaniline. AB - N-Nitroso-N-methylaniline (NMA) is a strong oesophageal carcinogen in rats but exhibits few overt genotoxic effects. Previous work from our laboratory established that NMA is readily metabolized by cytochrome P450-catalysed N demethylation to produce the benzenediazonium ion (BDI), a relatively stable but reactive electrophilic agent. We have also shown that BDI reacts with DNA to form an acid-labile adduct. We have now shown that BDI, generated chemically or by the metabolism of NMA in vitro, reacts with DNA to form a triazene coupling product at the N6-position of adenine residues. This adduct has also been shown to be produced in the liver DNA of rats treated with NMA. Procedures for the isolation of DNA and for analysis of the adduct are presented. PMID- 1855879 TI - Metabolic denitrosation of N-nitrosamines: mechanism and biological consequences. AB - NADPH-dependent microsomal metabolism of N-nitrosamines results in both oxidative dealkylation and denitrosation of the molecule. For denitrosation, two enzymatic mechanisms have been proposed: (i) cytochrome P450 (P450)-dependent one-electron reduction of the nitrosamine molecule, resulting in the formation of nitric oxide (NO) and secondary and primary amine, and (ii) liberation of NO via an oxidative mechanism mediated by a P450-dependent one-electron abstraction. In order to clarify the mechanism of denitrosation, the metabolism and kinetics of N nitrosodibenzylamine (NDBzA) and its corresponding secondary amine dibenzylamine were studied. The main metabolites of NDBzA are benzaldehyde, the primary amine benzylamine and nitrite. An important finding is that benzaldehyde is generated more rapidly from dibenzylamine than from the parent NDBzA. During reductive denitrosation of NDBzA, the oxygen atom in benzaldehyde is derived from air, while benzaldehyde generated via the oxidative mechanism of denitrosation receives its oxygen atom from water due to hydrolysis of the intermediary benzylidenebenzylamine. Microsomal incubation of NDBzA in buffer containing 18O H2O resulted in no incorporation of 18O from water into benzaldehyde, which could be related to the formation of the corresponding benzaldehyde, which could be related to the formation of the corresponding benzylidenebenzylamine. It is concluded that NDBzA is denitrosated by the proposed reductive mechanism. Current belief is that denitrosation leads to detoxification of the NA molecule; however, toxic effects cannot be excluded if the conversion of NO into NO2- and NO3- involves intermediary formation of the NO2 radical.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855880 TI - Subcellular fractions of rat organs contain nitroreductases which reduce N nitrodimethylamine to N-nitrosodimethylamine. AB - The nasal carcinogen N-nitrodimethylamine was reduced to its N-nitroso analogue N nitrosodimethylamine in vivo. Liver-soluble fraction and brain mitochondria contained enzymes capable of reducing this compound. The activity was only partly inhibited by oxygen; NADPH and NADH served as cosubstrates. N-Nitromethylamine is also carcinogenic and was reduced by liver cytoplasm to a protein binding species (methyldiazohydroxide?). PMID- 1855881 TI - Toxicokinetic studies of N-nitrosamine carcinogenesis. PMID- 1855882 TI - Enzyme kinetics of N-nitrosodimethylamine demethylase in rodents and humans. AB - A variety of Km values have been reported for hepatic microsomal N nitrosodimethylamine demethylase (NDMAd). We demonstrated previously that the biologically important, high affinity (KmI) form of microsomal NDMAd is manifested by cytochrome P450IIE1 (also known as P450ac and P450j). The KmI value of NDMAd was, however, affected greatly by assay conditions: the possible presence of inhibitors and the presence of cytochrome b5. We re-examined the KmI value by testing the effect of enzyme concentrations and of different types of enzyme preparations on the Km. The KmI value ranged from 15 to 22 microM, as estimated by the direct linear plot, using a microsomal protein concentration in the range of 0.1 to 0.8 mg/ml with correction for substrate utilization. A slight yet significant dependency of microsomal protein concentration on the Km (r = 0890; p less than 0.05) was seen. When five different microsomal preparations were compared, the KmI value ranged from 14 to 24 microM (median, 20 microM), as estimated by the direct linear plot. The Km estimated by the commonly used Eadie Hofstee plot did not differ from that by the direct linear plot. These Km values are close to the values obtained in studies with isolated cells and tissue slices. The KmI form of NDMAd (P450IIE1 and its orthologues) is present in rats, mice, rabbits, hamsters and guinea-pigs. It is responsible for the age-dependent differences between rats and hamsters and for the sex-related differences in mouse kidneys, and for the bioactivation and toxicity of NDMA. This enzyme also exists in human liver microsomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855883 TI - Acceleration of N-nitrosation reactions by electrophiles. AB - Selected mechanisms by which electrophiles can facilitate N-nitrosamine formation are reviewed. Special attention is given to a recently discovered reaction in which nitrogen in its lowest (ammonia) oxidation state is efficiently converted to N-nitroso compounds by oxidation in the presence of secondary amines; an electrophilic transition metal centre (E+) makes this reaction possible by initially N-coordinating the ammonia (E+ + NH3----E-NH3+). Other mechanisms considered include: the conversion of nitrite under nonacidic conditions via nitro complexes to nitrosatively active transition metal nitrosyl intermediates (E+ + NO(2-)----E-NO(2-)----E-NO2+); catalysis of N-nitrosamine formation in nitrite-amine mixtures by electrophilic carbon centres that initiate the reaction by attack on the amine (E+ + R2NH----E-NR2); and coordination of nitrite by carbon electrophiles to form activated O-bound species (E+ + ONO(-)----E-O-NO) capable of performing the required N-nitrosation. The findings suggest that acceleration of N-nitrosamine-forming reactions by electrophiles may be a critical factor to consider in attempting to rationalize, predict and control the distribution of carcinogenic N-nitroso compounds in vivo and in the environment. PMID- 1855884 TI - Nitrosamine activation and detoxication through free radicals and their derived cations. AB - The enzymatic activation of simple dialkylnitrosamines is widely perceived to involve cytochrome P450-mediated alpha-hydroxylation to generate an unstable alpha-hydroxynitrosamine. This process can also result in the denitrosation of the nitrosamine, presumably through a common intermediate. We present evidence that the critical intermediate is the alkynitrosaminomethyl free radical, which we generated by thermal decomposition of a nitrosamino acid perester. The radical rapidly loses NO to generate an N-alkylmethyleneimine. The radical is also produced during the Ce(IV) oxidation of beta-hydroxynitrosamines after fragmentation, where it not only loses NO but is oxidized further to a cation which reacts with water to form an alpha-hydroxynitrosamine. These results provide models of the activation and detoxication pathways for beta-oxidized nitrosamines. PMID- 1855885 TI - Alkylating potency of nitrosated amino acids and peptides. AB - The alkylating potency of unstable N-nitrosamino acids and N-nitrosopeptides was investigated in vitro using 4-(para-nitrobenzyl)pyridine (NBP) as nucleophile. Of the amino acids, Met and those with an aromatic side chain were the most potent. The relative overall alkylating potency was 23:10:5:4:2:1: for Trp, Met, His, Tyr, Phe and Gly, respectively. The homo-dipeptides were much more potent than the amino acids, with relative potencies of 400:110:100:8:3:1, for Trp-Trp, Tyr Tyr, Met-Met, Asp-Asp, Phe-Phe and Gly, respectively. In the one-phase reaction system (in which NBP is already present during the nitrosation reaction at acidic pH), all amino acids tested showed a second-order reaction for nitrite. In the two-phase system (in which NBP is added only after bringing the nitrosation reaction mixture to neutrality), all amino acids tested except one again showed a second-order reaction for nitrite (Phe, His, Asp and the dipeptide artificial sweetener aspartame); only Met under these conditions had a reaction order of one for nitrite. This could mean that nitrosation of the side chain of Met produces a second N-nitroso product which is relatively stable in acid but reacts with NBP under neutral conditions. In the human stomach, this side-chain nitrosation might become more important than the reactions at the primary amino group, firstly because of the greater stability of the product(s) in acid and secondly because of the first-order reaction rate for nitrite.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855886 TI - Nasopharyngeal carcinoma: epidemiology and dietary factors. AB - Nasopharyngeal carcinoma (NPC) is a disease with a remarkable racial and geographical distribution. It is very rare (incidence of less than 1 per 100,000 person-years) in most parts of the world, and in only a handful of populations does this low-risk profile deviate; these groups include people in southern China, Eskimos and other natives of the Arctic region, natives of south-east Asia, and the mainly Arab populations of North Africa and Kuwait. Convincing evidence implicates dietary factors as the primary cause of NPC among Chinese. A series of case-control studies conducted in various Chinese populations with distinct risks of NPC, ranging from the very high-risk Cantonese populations to the relatively low-risk northern Chinese, have suggested that ingestion of salted fish and other kinds of preserved foods constitutes the most important cause of NPC among these people. Preliminary data on Malays in south-east Asia, Eskimos in Alaska and Arabs of North Africa also suggests that ingestion of preserved foods by these population groups may be responsible for their raised incidence of NPC. PMID- 1855887 TI - Use of monoclonal antibodies to identify cytochrome P450 isozymes in rat liver microsomes that hydroxylate N-nitrosomethylamylamine at each of six positions. AB - Inhibition of enzyme activity by monoclonal antibodies (MAbs) was used to indicate which cytochrome P450 isozymes in Sprague-Dawley rat liver microsomes catalyse hydroxylation of the oesophageal carcinogen N-nitrosomethyl-n-amylamine (NMAA) to give 2- to 5-hydroxy-NMAA (HO-NMAA), formaldehyde and pentaldehyde. Liver microsomes (0.3-0.6 mg protein) were incubated (15 min, 23 degrees C) with 0.4 mg MAb and, after adding NMAA to 6 mM, incubated for 20 min at 37 degrees C. Mixtures were analysed for HO-NMAAs by gas chromatography-thermal energy analysis and for aldehydes by high-performance liquid chromatography of their 2,4 dinitrophenylhydrazones. The percentage inhibition by each MAb indicates the percentage metabolism by the corresponding P450 isozyme(s). These results indicate that the MAb to P450 IIB1 cross-reacts with P450 IIE1 and that the MAb to male-specific constitutive IIC11 cross-reacts with female-specific IIC12. Taking this into account, the main results were as follows. With uninduced male microsomes, 4-hydroxylation was catalysed mainly by IIC11 and demethylation by IIC11 and IIE1. With uninduced female microsomes, P450s reacting with the MAb to IIC11 (probably mainly IIC12) were responsible for most of the 4-hydroxylation and demethylation. With 3-methylcholanthrene-induced male microsomes, most 3 hydroxylation and some depentylation were due to IA1 or IA2. With phenobarbital induced microsomes, all six reactions, but especially 4-hydroxylation and depentylation, were largely due to IIB1. With Aroclor-induced microsomes, all six reactions were catalysed by IIB1 and IA1 or IA2. The role of P450 IIC11 in 4 (omega-1)-hydroxylation was striking. PMID- 1855888 TI - Participation of phenobarbital-inducible cytochrome P450 in the mutagenic activation of N-nitrosopropylamines by liver and lung 9000 g fractions from five animal species and man. AB - The mutagenicity of nine carcinogenic N-nitrosopropylamines was studied by the Ames preincubation assay using 9000 g supernatant (S9) fractions or alcohol dehydrogenase. Treatment of animals with polychlorinated biphenyls or phenobarbital resulted in a marked increase in the ability of liver S9 to activate N-nitrosobis(2-hydroxypropyl)amine, N-nitroso(2-hydroxypropyl)(2 oxopropyl)amine, N-nitrosobis(2-oxopropyl)amine, N-nitrosobis(2 acetoxypropyl)amine, N-nitroso-2,6-dimethylmorpholine, N-nitroso(2 hydroxypropyl)methylamine, N-nitroso(2-oxopropyl)methylamine, N-nitroso(2,3 dihydroxypropyl)methylamine and N-nitroso(2,3-dihydroxypropyl)(2 hydroxypropyl)amine to mutagens, whereas 3-methylcholanthrene induction was not effective. All reactions required NADP as a cofactor for mutagenic activation, and nitrogen, carbon monoxide, cytochrome c and metyrapone considerably inhibited their mutagenic activities, whereas 7,8-benzoflavone did not. Five propanol derivatives were not mutagenic in the presence of NAD and alcohol dehydrogenase. We conclude that the phenobarbital-inducible major cytochrome P450 in liver S9 from five animal species tested was selectively involved in mutagenic activation. The same cytochrome in human liver S9 and in lung S9 from three rodent species also activated the mutagenicity of N-nitroso(2-hydroxypropyl)methylamine. PMID- 1855889 TI - Biological and chemical properties of alkanediazotates as active species of N nitroso compounds. AB - The mutagenicity and chemical reactivity of (E)- and (Z)-potassium alkanediazotates, as precursors of corresponding alkanediazohydroxides, were investigated. In three microbial strains, Salmonella typhimurium TA1535 and Escherichia coli WP2 and WP2hcr-, the effect of changing the alkyl group on mutagenic potency was similar for (E)- and (Z)-diazotates, N-alkyl-N-nitrosoureas and alpha-hydroxynitrosamines. The capacity to alkylate nicotinamide, measured in an aqueous phosphate buffer, decreased with increasing alkyl chain length. Specific mutagenicity in S. typhimurium TA1535 was linearly related to alkylating activity. These results confirm that alkanediazohydroxides are the active alkylating species of N-nitroso compounds, and that their mutagenicity is determined by their alkylating activity. PMID- 1855890 TI - Activity of O6-alkylguanine-DNA alkyl transferase in the liver, kidney and white blood cells of rats of different ages. AB - Age-related differences in the sensitivity of rats to alkylating carcinogens may be dependent on various factors, including the cellular levels of O6-alkylguanine DNA alkyltransferase (AT). In the present study, the levels of AT were measured in protein extracts prepared from liver, kidney and peripheral white blood cells of male outbred rats aged 1, 4, 14, 22 and 36 months. The AT level (expressed as activity per milligram protein) in liver extracts was lower in rats aged 1, 4 or 36 months than in extracts prepared from rats aged 14 or 22 months. This observation of a variation in AT level with age is in agreement with our previous results. The AT levels in kidney and white blood cells did not differ significantly with age, and in all cases the AT levels were lower than those observed in the liver extracts, the kidney extracts having more AT activity than the white blood cell extracts. The total protein content of both liver and kidney tissues, calculated per gram of wet tissue, increased to a maximum at 14 months and subsequently declined, the total protein content being always higher in the liver than in the kidney. In contrast, the DNA content per gram of wet tissue was highest in young animals and subsequently declined to a minimum at 14 months. The implications of this inverse relationship to the levels of AT activity are discussed. PMID- 1855891 TI - Excision of imidazole ring-opened N7-hydroxyethylguanine from chloroethylnitrosourea-treated DNA by Escherichia coli formamidopyrimidine-DNA glycosylase. AB - Alkylkation of the N7 of guanine residues in DNA favours the opening of the imidazole ring, yielding a formamidopyrimidine (Fapy). This Fapy residue blocks DNA replication and is actively excised by a DNA glycosylase. We have cloned and sequenced the Escherichia coli gene responsible for synthesis of the enzyme, which has also been purified to homogeneity. It was found to have associated apurinic/apyrimidinic (AP) lyase activity, nicking DNA at AP sites. Chloroethylnitrosoureas are used in cancer chemotherapy. The lesions induced in DNA by these compounds, including N7-chloro- and hydroxyethylguanine, are excised by E. coli 3-methyladenine DNA glycosylase II, and we report that the corresponding imidazole ring-opened forms are repaired by Fapy-DNA glycosylase. Human cells have the counterpart to these enzymes, which could contribute to the repair of these lesions during chemotherapy. PMID- 1855892 TI - Resistance to N-nitroso compounds in cells treated with various physical and chemical agents. PMID- 1855893 TI - Distribution and excretion of 3H-sterigmatocystin in rats. AB - In order to investigate the distribution and excretion of sterigmatocystin, a carcinogenic mycotoxin, radioactively labelled compound was studied in rats. The highest concentration of radioactivity in serum appeared 3 h after administration of 0.5 microCi/g bw. The half-lives of distribution and excretion were 0.51 h and 43.9 h, respectively. The radioactivity was concentrated mainly in liver, stomach, kidney, duodenum and lung and to a lesser extent in fat, muscle, testis, rectum and bone. By 48 h, 56.4% had been excreted in faeces and 20.1% in urine. Biliary excretion may be the major route of excretion of sterigmatocystin. PMID- 1855894 TI - Nitrotyrosine as a new marker for endogenous nitrosation and nitration. AB - A sensitive and selective method has been developed for analysing 3-nitrotyrosine (NTTYR), an exposure marker for exogenous and endogenous nitrosating or nitrating agents, in tissue and blood proteins by gas chromatography-thermal energy analysis. Using this method, a number of kinetic studies were carried out. Free and protein-bound tyrosine were reacted easily to yield NTTYR. The method was also applied to the study of NTTYR formation in vivo; a dose-dependent increase in NTTYR was seen in both plasma proteins and haemoglobin obtained from rats 24 h after intraperitoneal injection of various doses (0.5-2.5 mumol/rat) of tetranitromethane. Major urinary metabolites of NTTYR, given orally to rats, were isolated and identified as 3-nitro-4-hydroxyphenylacetic acid (NHPA) and 3-nitro 4-hydroxyphenyllactic acid. About 44% and 5% of the oral dose of NTTYR (100 micrograms/rat), respectively, was excreted as these metabolites. Some human urine samples were analysed for NHPA by gas chromatography-thermal energy analysis after ethyl acetate extraction and high-performance liquid chromatography purification; 2.8 +/- 2.3 (mean +/- SD; n = 11) micrograms/24 h, ranging from 0-7.9 micrograms/24 h, were detected (detection limit, 0.2 micrograms/l). In conclusion, NTTYR in proteins or its metabolites in urine could be readily analysed by gas chromatography-thermal energy analysis as a new, additional marker for endogenous nitrosation and nitration. PMID- 1855895 TI - Lung cancer and the changing cigarette. AB - Epidemiological studies have shown that the long-term smoker of low-yield cigarettes has a 20-50% lower risk of lung cancer than the smoker of high-yield cigarettes. This risk reduction is attributed to changes in the make-up of cigarettes and especially to the introduction of filter tips. Other changes relate to the use of tobaccos that produce lower smoke yields, including reconstituted and expanded tobaccos, as well as utilization of porous cigarette paper and perforated filter tips. New developments in the make-up of commercial cigarettes must be monitored in order to prevent unfavourable introductions. Although a smoke-free society should be the major public health goal, recent consumer statistics do not support this goal. Thus, a strong social case is made for further developments in the low-yield cigarette. PMID- 1855896 TI - Environmental determinants of lung cancer in Shenyang, China. AB - To investigate determinants of the high rates of lung cancer in Shenyang, an industrial city in north-eastern China, a case-control study was conducted. Interviews with 1249 lung cancer patients and 1345 population-based controls revealed that cigarette smoking was the main cause of lung cancer. Smoking accounted for 55% of the lung tumours in men and 37% in women. In addition, air pollution from coal-burning heating and cooking devices was significantly linked to lung cancer, with risks rising in proportion to duration of exposure to indoor pollutants. Measurement of benzo[a]pyrene revealed average wintertime levels in air that were nearly 60 times the recommended upper limit for US cities, with even higher concentrations indoors in traditional single-storey homes using coal burning kang (stoves). Occupational factors were also involved, the risk being elevated by three fold among smelter workers. Soil levels of arsenic and other metals rose with increasing proximity to the Shenyang copper smelter, and elevated risks of lung cancer were found among men, but not women, living within 1 km of its central stacks. Prior nonmalignant lung disease was common and was reported more often among the lung cancer patients than among controls. The findings suggest that cigarette smoking and environmental pollutants combine to account for most of the excess risk of lung cancer in this population. PMID- 1855897 TI - Betel quid and oral cancer: prospects for prevention. AB - Betel-quid chewing is an ancient and socially accepted practice. The introduction of tobacco reinforced this practice, and now almost all habitual chewers of betel quids include tobacco. It is well established that chewing of betel quid with tobacco causes oral cancer and is largely responsible for the high incidence of oral cancer in several South Asian countries. The feasibility of primary prevention of oral cancer was studied in a population-based prospective intervention study. A cohort of 12,212 betel-quid chewers and smokers was exposed to a programme of health education for stopping chewing and smoking and subjected to annual examinations for detection of oral precancerous lesions. Evaluations after one, five and eight years showed that primary prevention of oral cancer is feasible and practicable. Early detection of oral cancer is an important control measure. In a secondary prevention study, 53 basic health workers were trained in the detection and referral of lesions suspected of being oral cancer. Over one year, they examined more than 39,000 high-risk individuals, resulting in the detection of 20 cases of oral cancer. The sensitivity and specificity of their diagnoses was assessed through a re-examination of a 5% sample: we concluded that it was possible to incorporate a secondary prevention programme into the existing health care system. PMID- 1855898 TI - Lung cancer: political measures. AB - In countries where prolonged smoking of manufactured cigarettes is a widely established habit, it is responsible for about 90% of lung cancer. As lung cancer is usually incurable, even with expensive technology, the key to its control lies in prevention. World experience has shown the crucial need for government commitment, funding and action in controlling the epidemic of tobacco-related disease. It is recommended that each country establish a national council of 'tobacco or health' to coordinate a comprehensive tobacco control programme. This programme should incorporate data collection, including evaluation of specific anti-tobacco measures; legislative measures, including strong, rotating health warnings, limits on harmful substances, establishment of smoke-free areas, bans on any new forms of tobacco use, and a total ban on all direct or indirect promotion of tobacco products; health education campaigns; and taxation and price policies. The support and involvement of the medical profession is vital. Obstacles to success include the effect of advertising revenue in silencing the media, the inertia of governments and the medical profession, but most importantly the tobacco industry--the largest, wealthiest, most determined and strongest opposition to tobacco control worldwide. PMID- 1855899 TI - Analysis and pyrolysis of some N-nitrosamino acids in tobacco and tobacco smoke. AB - A new tobacco-specific nitrosamine, 4-(N-nitrosomethylamino)-4-(3-pyridyl)butyric acid (iso-NNAC), has been identified in tobacco, and its structure was confirmed by gas chromatography-mass spectrometry following enrichment of a tobacco extract. The levels of iso-NNAC ranged from 0.01 to 0.95 ppm. It does not induce DNA repair in primary rat hepatocytes and is inactive as a tumorigenic agent in strain A mice. In order to study the fate of nitrosamino acids during smoking, we spiked cigarettes with the following N-nitrosamino acids: iso-NNAC, 3 (nitrosomethylamino)propionic acid (NMPA), 4-(nitrosomethylamino)butyric acid (NMBA), N-nitrososarcosine (NSAR) and N-nitrosoproline (NPRO). NMPA and NMBA were partially transferred, unchanged, during smoking and partially formed the corresponding methyl esters, while pyrolysis of NSAR and NPRO resulted mainly in their decarboxylating products. This is the first time that the pyrosynthesis of methyl esters has been observed during smoking. PMID- 1855900 TI - Aflatoxins: data on human carcinogenic risk. AB - Some of the major difficulties in assessing the role of aflatoxin (AF) in the causation of liver cancer are discussed. Firstly, exposure to AF in Africa and parts of Asia and Latin America might begin very early in life and episodically thereafter. The number of episodes and the degree of exposure to AF varies greatly by country and region, by agricultural and crop storage practices, by season and by other factors difficult to control in any questionnaire-based study. Secondly, there is a high geographical correlation between exposure to AF and to hepatitis B virus. Thirdly, long-lasting biological markers for AF are still not available. Epidemiological studies might be enhanced by the incorporation of new biological assays. It is to be hoped that better information will be generated as a result of on-going intervention projects, such as reduction of AF levels and agricultural development programmes, and by monitoring exposure to AF and the incidence of liver cancer in areas where hepatitis B virus vaccination is effectively reducing the prevalence of carriers of the viral surface antigen. PMID- 1855901 TI - Studies in tobacco carcinogenesis. AB - The vapour phase of freshly generated cigarette mainstream smoke, of sidestream smoke and of environmental tobacco smoke was analysed for such tumorigenic agents as benzene, 1,3-butadiene and acrolein with a newly developed, highly sensitive gas chromatography-mass selective detection method. The major carcinogen in tobacco smoke, catechol, was studied in regard to its specific action on the metabolism of benzo[a]pyrene in mouse lung and mouse skin. The major tobacco specific carcinogens in tobacco and its smoke are the nicotine-derived N nitrosamines, N'-nitrosonornicotine and 4-(nitroso-methylamino)-1-(3-pyridyl)-1 butanone. A third nitrosamine that can be formed in vitro by nitrosation of nicotine is 1-(nitrosomethylamino)-1-(3-pyridyl)butylaldehyde. This aldehyde is not present in tobacco products, but its noncarcinogenic oxidation product, 4 (nitrosomethylamino)-1-(3-pyridyl)butyric acid, was found in tobacco and can be formed from the major nicotine metabolite, cotinine. It is also likely that this acid can be formed by endogenous reactions. PMID- 1855902 TI - Carcinogenic substances in Soviet tobacco products. AB - Chemical carcinogens were determined in mainstream smoke from nonfilter cigarettes produced and consumed in the USSR and in nass, a mixture of tobacco, lime, ash and cotton oil. Cigarettes contained high levels of tar (23-25 mg/cigarette) and nicotine (1.5-1.9 mg/cigarette) and, generally, a high content of polycyclic aromatic hydrocarbons, which are major epithelial carcinogens, N nitrosamines, which are organ-specific carcinogens, and some carcinogenic metals, such as arsenic and chromium. Nass contained the tobacco-specific N-nitroso compounds, N'-nitrosonornicotine, N'-nitrosoanatabine, N'-nitrosoanabasine and 4 (N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone, as well as volatile N nitrosamines, but at levels lower than in other types of chewing tobacco and snuff. The low levels in nass are due to the short ageing process used, in contrast to commercially produced chewing tobacco and fine-cut snuff, which are highly processed products requiring long ageing and fermentation. PMID- 1855903 TI - Tobacco-specific nitrosamines in commercial cigarettes: possibilities for reducing exposure. AB - Tobacco-specific nitrosamines (TSNA) are powerful carcinogens found in tobacco and tobacco smoke in relatively high concentrations. Tar delivery, which is generally accepted as an index for the carcinogenic potential of cigarette smoke, must be declared in most European countries. In this investigation of more than 170 types of commercial cigarettes from several European countries and the USA, no correlation was observed between tar delivery and mainstream smoke concentration of N'-nitrosonornicotine (NNN) and 4-(N-nitrosomethylamino)-1-(3 pyridyl)-1-butanone (NNK). Therefore, although crucial, tar delivery alone is not a sufficient index for the carcinogenic potential of cigarette smoke. It is proposed that TSNA concentrations be determined for characterization of the carcinogenic potential of cigarettes with low and ultra-low tar yields and that these be declared by an additional and adequate parameter. The mainstream smoke concentrations of NNN and NNK are given by the amounts of preformed compounds in tobacco, which is dependent on the nitrate content of the tobacco and the tobacco type. A further important determinant of the exposure of smokers to TSNA is the total volume drawn through a cigarette while smoking, which is dependent on puff volume and puff frequency and which directly influences TSNA transfer. Smokers inhale higher volumes when smoking low-nicotine cigarettes, so that low NNN:nicotine and NNK:nicotine ratios result in decreased exposure to TSNA. Reduction of exposure to TSNA can be achieved by selecting tobaccos with low levels of preformed TSNA (low nitrate content, small amounts of burley tobaccos and stems) and by manufacturing cigarettes with low NNN:nicotine and NNK:nicotine ratios. PMID- 1855904 TI - Occurrence of and exposure to N-nitroso compounds in tobacco. AB - The concentrations of 21 N-nitroso compounds in smokeless tobaccos are presented. Tobacco-specific nitrosamines accounted for 70-90% of the total identified N nitroso compounds. Daily exposure of smokeless tobacco users to preformed N nitroso compounds may exceed 200 micrograms/day in certain populations. PMID- 1855905 TI - Localization of DNA adducts formed in the nasal cavity of the rat by the tobacco specific nitrosamine 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK). AB - The tissue localization of the DNA adducts O6- and 7-methylguanine induced in the nasal cavity by the nicotine-derived carcinogen 4-(N-nitrosomethylamino)-1-(3 pyridyl)-1-butanone (NNK, 30 mg/kg intraperitoneally) has been investigated immunocytochemically in male Sprague-Dawley rats. Adduct-specific nuclear staining, indicative of the metabolic activation of NNK to a methylating compound, was observed in both respiratory and olfactory mucosa. In the respiratory epithelium, strong staining was generally observed in areas devoid of goblet cells. Less intense staining was observed both in the serous gland cells and their efferent ducts in the respiratory submucosa, whereas the mucous gland cells were unstained. In the olfactory mucosa, the sustentacular and basal cells of the olfactory epithelium were moderately stained; staining varied substantially from site to site. No DNA adduct was detected in the olfactory cells. Strong nuclear staining, similar to that in the respiratory mucosa, was observed in the cells of the Bowman glands of the olfactory submucosa. A similar distribution of methylated DNA bases in nasal tissues has been observed in rats after exposure to other N-nitrosamines and in Syrian hamsters after exposure to NNK. This finding may indicate that in man the same cell types undergo DNA adduct formation after exposure to NNK and other N-nitrosamines. PMID- 1855906 TI - Feasibility of a prospective study of smoking and mortality in Qidong, China. AB - Qidong is a rural county in eastern China with particularly good facilities for epidemiological research: cigarette use by adult males is widespread (70% now smoke), male lung cancer rates already appear to be rising, the population is stable and well served by a county-wide network of health care facilities, and systematic county-wide registration of all deaths has existed since the mid 1970s, causes currently being assigned according to the 9th International Classification of Diseases. PMID- 1855907 TI - Characterization of activation and deactivation pathways of 4-(N nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) in rat hepatocytes. AB - We have characterized the metabolism of 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1 butanone (NNK) in cultured rat hepatocytes and have established the relationship between various metabolic pathways and single-strand breaks (SSB) in DNA. Metabolism of [5-3H]-NNK by carbonyl reduction, alpha-carbon hydroxylation and pyridine N-oxidation was linear from 0.5 to 6 h with 0.25-2 x 10(6) hepatocytes. Using an alkaline elution assay, we observed that NNK induces SSB in DNA in a dose- and time-dependent manner. SSB induced by NNK were rejoined partially within 2 h and totally by 12 h after exposure. NNK-N-oxide produced a smaller number of SSB than NNK, suggesting that pyridine N-oxidation of NNK is a deactivation pathway. Carbonyl reduction of NNK led to 4-(N-nitrosomethylamino)-1 (3-pyridyl)-1-butan-1-ol (NNAl). Reaction of NNK with methyl magnesium iodide gave 4-(N-nitrosomethylamino)-1-(methyl)-1-(3- pyridyl)butanol-1-ol (1-MeNNAl) 82% yield. NNAl, but not 1-MeNNA1, can be reoxidized to NNK. Doses of 5 mM NNAl and 1-MeNNAl both induced SSB, indicating that NNAl does not require reconversion to NNK to be activated to DNA damaging intermediates. alpha-Methylene hydroxylation resulted in the formation of 4-oxo-4-(3- pyridyl)butanal. At equimolar concentration (5 mM), the aldehyde was more damaging than NNK to hepatocyte DNA. The results of this study demonstrate that NNK is activated by rat hepatocytes and that metabolites formed by alpha-carbon hydroxylation induce SSB. PMID- 1855908 TI - Activation of N'-nitrosonornicotine by hydrogen peroxide in vitro. AB - Betel-quid ingredients were found to produce reactive oxygen species, such as superoxide anion and hydrogen peroxide, in vitro. We demonstrated that N' nitrosonornicotine (NNN) can be converted to its active metabolite, hydrogen peroxide, nonenzymatically in the presence of ferrous ions and ethylenediaminetetracetic acid (EDTA) at pH 7.2. Three ultimate metabolites of NNN--NNN-1-N-oxide, 4-hydroxy-4-(3- pyridyl)butyric acid and 4-oxo-4-(3 pyridyl)butyric acid--and nornicotine were detected by high-performance liquid chromatography. 3H-NNN and 14C-NNN interact with calf thymus DNA in the presence of hydrogen peroxide, ferrous ion and EDTA. The results suggest that formation of reactive oxygen species in the presence of NNN may be a key factor in the initiation of oral tumours in tobacco and betel-quid chewers. PMID- 1855909 TI - Antimutagenic and anticarcinogenic effects of betel leaf extract against the tobacco-specific nitrosamine 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK). AB - Earlier studies showed that betel leaf inhibits the mutagenic action of standard mutagens like benzo[a]pyrene and dimethylbenz[a]anthracene. Since tobacco specific nitrosamines are the major carcinogens present in unburnt forms of tobacco, we studied the effect of an extract of betel leaf on the mutagenic and carcinogenic actions of one of the most potent, 4-(N-nitrosomethylamino)-1-(3 pyridyl)-1-butanone (NNK). Betel-leaf extract and hydroxychavicol suppressed the mutagenicity of NNK in both the Ames and the micronucleus test. In studies in mice, betel-leaf extract reduced the tumorigenic effects of NNK by 25%. Concurrent treatment with the extract also inhibited the decreases in levels of vitamin A in liver and plasma induced by NNK. Betel leaf thus has protective effects against the mutagenic, carcinogenic and adverse metabolic effects of NNK in mice. PMID- 1855910 TI - Effect of vitamin A status of rats on metabolizing enzymes after exposure to tobacco extract or N'-nitrosonornicotine. AB - The effects of N'-nitrosonornicotine (NNN) and tobacco extract on hepatic and pulmonary biotransformation enzymes were studied in rats fed vitamin A-sufficient or -deficient for semisynthetic diets. Basal levels of cytochrome P450, benzo[a]pyrene hydroxylase, benzphetamine demethylase, glutathione S-transferase and glutathione were lower in the group on the deficient diet. Treatment with tobacco extract or NNN significantly increased the levels of these enzymes in the sufficient diet group. However, in the deficient group, phase I enzymes were significantly increased, but glutathione and glutathione S-transferase levels were drastically reduced. Urine from animals on the deficient diet and treated with tobacco extract or NNN were mutagenic in the Ames Salmonella/microsome test. The results suggest that altered metabolism resulting from a vitamin A-deficient diet may be an important factor in susceptibility to carcinogens. PMID- 1855911 TI - Inhibition of tobacco-specific nitrosamine 4-(N-nitrosomethylamino)-1-(3-pyridyl) 1-butanone (NNK) tumorigenesis with aromatic isothiocyanates. AB - 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent tobacco specific carcinogenic nitrosamine. At low doses, it induces primarily lung tumours in mice, hamsters and rats, regardless of the route of administration. Its unique organ specificity and potency suggest its possible role in the high incidence of lung cancer in smokers. The goal of this study was to find agents that would potentially prevent NNK tumorigenesis. Previous results led us to test phenethyl isothiocyanate (PEITC) on NNK tumorigenesis in a two-year bioassay in Fischer 344 rats. The NNK-treated group developed 80% lung tumour incidence, whereas NNK-treated rats fed PEITC diets had only 40% lung tumour incidence. Incidences in other organs were not affected by this treatment. We also tested PEITC in a 16-week, short-term bioassay against NNK-induced lung adenomas in A/J mice. Pretreatment of mice with PEITC by gavage at four daily doses of 5 mumol or 25 mumol reduced the formation of NNK-induced lung adenomas by 70% or 100%, respectively. Interestingly, benzyl isothiocyanate and phenyl isothiocyanate, the lower homologues of PEITC, were inactive in this bioassay. Using a protocol similar to that used in the bioassays, PEITC was shown to decrease DNA methylation by NNK in the lungs of rats and mice and suppress the metabolism of NNK by mouse lung microsomes. These results are consistent with the previous data, suggesting that the inhibition of NNK-induced lung tumour formation by PEITC is a consequence of reduced DNA methylation caused by inhibition of NNK metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1855912 TI - Modulation of genotoxic activity of tobacco smoke. AB - Tobacco smoke (TS) caused a three- to nine-fold increase in the frequency of his+ revertants in Salmonella typhimurium TA98 but not in TA97a, TA100 or TA102. Activation by a post-mitochondrial fraction obtained from the liver of rats pretreated with Aroclor-1254 or methylcholanthrene was required; fractions from phenobarbital-pretreated or untreated rats had no effect. Vitamins A and E, but not ascorbic acid, inhibited the TS-induced mutagenesis by up to 63%, whereas glutathione and cysteine increased it slightly. Na2SeO3, but neither CoCl2 nor caffeine, inhibited the mutagenic effect of TS by 46-56%. In Chinese hamster ovary cells, both Na2SeO3 and caffeine strongly potentiated the number of chromosomal aberrations induced by TS, while theophilline slightly reduced its clastogenic effect. Treatment of mice with TS for 60 min/day increased the frequency of micronuclei in polychromatic erythrocytes in bone marrow and in fetal liver and the number of NCE micronuclei in peripheral blood by four to five fold. Simultaneous treatment of mice with TS and Na2SeO3 reduced the clastogenic effect of TS. Ascorbic acid had no effect on clastogenicity but reduced toxicity as measured by body weight loss. Both Na2SeO3 and ascorbic acid suppressed the induction of TS-induced hyperplastic and metaplastic changes in bronchial mucosa but had no effect on the number of urethane-induced lung adenomas. Vitamins A and E and ascorbic acid may have a protective effect against the toxic and genotoxic activities of TS. PMID- 1855913 TI - N-nitroso compounds and tobacco-induced cancers in man. AB - Human exposure to N-nitroso compounds in tobacco products is more intense and widespread than from any other known source. This paper presents evidence that two of these N-nitroso compounds, 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1 butanone and N'-nitrosonornicotine are involved in causing cancers of the oral cavity, lung, oesophagus and pancreas in tobacco users. The reduction or elimination of these nitrosamines from tobacco products would probably lead to a decrease in the incidence of these cancers. PMID- 1855914 TI - Chinese tea inhibits the occurrence of oesophageal tumours induced by N nitrosomethylbenzylamine and blocks its formation in rats. AB - Chinese tea can inhibit the occurrence of oesophageal tumours not only by blocking the formation of N-nitrosomethylbenzylamine (NMBzA) in vivo, but also by inhibiting the carcinogenesis of preformed NMBzA. The incidence of oesophageal tumours in rats intubated with preformed NMBzA (5 mg/kg bw per week) and with the precursors of NMBzA (methylbenzylamine, 1 mM/kg bw; nitrite, 0.5 mM/kg bw) without Chinese tea was higher than in tea-treated groups; the same tendency was found with regard to the severity of the oesophageal lesions. The anticarcinogenic effects of five varieties of Chinese tea were different from one another. PMID- 1855915 TI - Inhibitory effect of Chinese tea on N-nitrosation in vitro and in vivo. AB - The inhibitory effect of 145 samples of Chinese tea on the formation of N nitrosomorpholine was studied in vitro. The rates of inhibition by green tea, crush, tear, curl (CTC) black tea, brick tea, jasmine tea, Oolong tea, sun-dried tea and black tea were positively correlated with their polyphenol contents. An inhibitory effect of green and black tea on endogenous N-nitrosation was also confirmed in humans. Drinking tea after a meal had a greater effect than drinking it before a meal. PMID- 1855916 TI - Some approaches to prevention of endogenous formation of N-nitrosamines in humans. AB - In a series of experiments on formation of N-nitrosamines from precursors in the gastric juice, we investigated individual nitrosation capacity and the influence of inhibitors on this process. In the presence of a molar ratio of 2:1 ascorbic acid:NaNO2, we found increased nitrosamine formation in 34% of gastric juice samples. Ferulic acid and caffeic acid generally suppressed nitrosation at high concentrations and stimulated it at low concentrations. The concentration at which the transition from a stimulating to an inhibitory effect occurs depends on individual differences in the gastric juice. PMID- 1855917 TI - Inhibition by fatty acids of direct mutagenicity of N-nitroso compounds. AB - Fatty acids inhibited the direct mutagenicity of N-nitroso compounds in Salmonella typhimurium TA1535, Escherichia coli WP2 and WPhcr-, and E. coli H/r30R (wild) and Hs30R (uvrA). This inhibitory activity was dependent on the concentration of fatty acids, and fatty acids with longer alkyl chain were more potent. Of the N-nitroso compounds tested, alpha-hydroxy nitrosamines underwent the strongest inhibitory effect. The rate of decomposition was not changed by addition of fatty acids. The partitioning property of the mutagens was altered but not to such a degree as to explain the amount of inhibition. No significant difference in alkylating activity of the N-nitroso compounds was observed in phosphate and acetate buffers. A stronger inhibition of mutagenicity by a butylating mutagen was detected in E. coli WP2 than in WP2hcr- and in E. coli H/r30R than in Hs30R, suggesting that excision repair was a possible mechanism of inhibition. The mutagenicity and cytotoxicity of alpha-hydroxy nitrosamines in Chinese hamster V79 cells were also inhibited by acetate. PMID- 1855918 TI - Potent inhibition of oesophageal metabolism of N-nitrosomethylbenzylamine, an oesophageal carcinogen, by higher alcohols present in alcoholic beverages. AB - The main cause of oesophageal cancer in western countries is consumption of alcoholic beverages, the degree of risk being much greater for certain spirits than for wine or beer. Risk shows a striking correlation with the content of higher alcohols in the drinks, although the alcohols per se have not been shown to be carcinogenic in experimental animals. To test the concept that higher alcohols modulate the oesophageal carcinogenicity of nitrosamines by altering their metabolism, we studied the effect of certain higher alcohols on the metabolism of N-nitrosomethylbenzylamine by rat oesophageal mucosal and liver microsomes. In oesophagus, the alcohols were 1000 times more inhibitory than ethanol, and in liver 100 times. This suggests that enhancement of carcinogenesis may not result from an effect on nitrosamine metabolism. Higher alcohols could act by increasing the rate of replication of cells already initiated for malignancy by previous exposure to nitrosamines. Intubation of 2-methylbutanol produces a very much greater increase in oesophageal basal-cell proliferation than does ethanol. PMID- 1855919 TI - Prevention of tumour production in rats fed aminopyrine plus nitrite by sea buckthorn juice. AB - Three groups of Wistar rats were fed a diet containing aminopyrine (0.2%) and NaNO2 (0.2%) and either tap-water (controls), sea buckthorn juice or ascorbic acid solution ad libitum for 38 weeks. All 17 rats given tap-water developed tumours in the liver, and six developed tumours in the lungs and four in the kidneys; in rats given sea buckthorn juice, 15 had tumours of the liver, 11 of the lungs and two of the kidneys; the incidences in rats given ascorbic acid were 18/18, 6/18 and 4/18, respectively. The average life span of the group given sea buckthorn juice was 270 days, which was significantly longer (p less than 0.01) than those of rats given tap-water (195 days) or ascorbic acid (220 days). Microscopic examination of the livers of rats receiving sea buckthorn juice showed fewer foci of carcinogenesis than those of the control and the ascorbic acid groups. The results suggest that sea buckthorn juice can block the endogenous formation of N-nitroso compounds more effectively than ascorbic acid and thereby prevent tumour production. PMID- 1855920 TI - Inhibition of bacterially mediated N-nitrosation by ascorbate: therapeutic and mechanistic considerations. AB - Ascorbate is known to inhibit the acid-catalysed N-nitrosation reactions of nitrite in the normally acid stomach, suggesting a useful therapeutic application of this compound to reduce exposure to the carcinogenic products of such reactions. However, in the achlorhydric stomach, which is particularly predisposed to cancer, increased exposure to endogenous N-nitroso compounds may result from bacterially catalysed reactions. The mechanism of these bacterially mediated reactions is only just beginning to be understood, and, indeed, more than one such mechanism may exist. Despite its usual lack of reactivity towards nitrite at neutral pH, ascorbate proved to be a potent inhibitor of the bacterially mediated (Pseudomonas aeruginosa) nitrosation of morpholine, competing with morpholine for the nitrosating agent elaborated by the bacteria from nitrite (the kinetics of the inhibition were classically competitive). This and other data, particularly with regard to the dependence of the bacterially mediated reaction on amine pKa, are discussed in relation to the potential mechanisms of these bacterially mediated reactions. PMID- 1855921 TI - Retinoids prevent epithelial carcinogenesis induced by N-nitroso compounds. AB - Two new retinoic acid esters and retinamides synthesized in China, N-(4 ethoxycarbophenyl)retinamide (RI) and N-(4-carboxyphenyl)retinamide (RII), significantly inhibited carcinogenesis induced in the epithelium of the forestomach of mice by N-nitrososarcosine ethyl ester. RI also markedly inhibited carcinogenesis induced in the epithelium of the oesophagus and forestomach in rats by this ester. No sign of hypervitaminosis was noticed with doses as high as six times the therapeutic dose. RI also inhibited precancerous and cancerous lesions in the nasal cavity and nasopharynx and oesophagus of rats induced by dinitrosopiperazine. In a malignant oesophageal epithelial cell line from rats, RE25-3, established in our laboratory, RI and RII inhibited mitosis, proliferation rate, chromosomal aberrations and incorporation of 3H-thymidine into DNA. The ability to form colonies on agar plates was also inhibited by these two compounds. PMID- 1855922 TI - Stability of mutagenic nitrosated products of indole compounds occurring in vegetables. AB - Levels of indolylglucosinolates in Brassica vegetables correlated significantly with the amounts of N-nitroso compounds formed in these vegetables after nitrite treatment. Nitrosation of indole-3-carbinol, indole-3-acetonitrile and indole, hydrolysis products of an indolylglucosinolate, resulted in formation of nitrosated products, which were directly mutagenic to Salmonella typhimurium TA100. The nitrosated products were unstable at pH 2 but stable at pH 8. Experiments to elucidate the mechanisms behind these differences in stability showed an equilibrium between the nitrosated indole compound and the free compound plus nitrite. PMID- 1855923 TI - New sulfenamide accelerators derived from 'safe' amines for the rubber and tyre industry. AB - A reduction of the high exposures to N-nitrosamines in the rubber and tyre industry is possible using the concept of 'safe' amines, in which vulcanization accelerators contain amine moieties that are both difficult to nitrosate and, on nitrosation, yield noncarcinogenic N-nitroso compounds. The toxicological and technological properties of more than 50 benzothiazole sulfenamides derived from 'safe' amines have been evaluated. Some of the new compounds show excellent vulcanization properties and seem suitable as replacements for traditional accelerators in this class of compounds. PMID- 1855924 TI - Tobacco smoking and its effect on health in China. AB - Production and sales of manufactured cigarettes are increasing in China; furthermore, the proportion of filtered cigarettes is still low, and the tar yield thus remains high. The prevalence of smoking in the general population aged 20 and over is estimated to be 68.9% of men and 8.3% of women. Case-control studies carried out in major cities in China all showed a close relationship between lung cancer incidence and smoking. In Shanghai, the population attributable risks for lung cancer due to smoking were 0.69 in men and 0.24 in women. A limited number of case-control studies indicate that the incidences of cancers of the bladder, oesophagus and pancreas are also associated with smoking. Some studies on coronary heart disease reveal unequivocally a significant risk for this disease associated with smoking. Cancer, chronic obstructive lung diseases and coronary heart disease are now important causes of death in some large cities in China. More comprehensive investigations are needed in order to evaluate thoroughly the effect of smoking on health in China. PMID- 1855925 TI - Biomonitoring of human exposure to alkylating agents by measurement of adducts to haemoglobin or DNA. AB - Recent analytical developments in the determination of adducts of DNA and protein with alkylating carcinogens are described which have considerably extended the number of carcinogens that can be examined. While sensitivity of detection equal to or better than one modified DNA base per 10(8) normal bases is now achievable for many specific alkylating carcinogens, further developments in the analytical methods are still needed for the identification and quantification of adducts derived from unknown and/or mixed exposures to carcinogens. PMID- 1855927 TI - Comparison of urinary nitrate, N-nitrosoproline, 7-methylguanine and 3 methyladenine levels in a human population at risk for gastric cancer. AB - We have measured the urinary excretion of nitrate, N-nitrosoproline, 3 methyladenine and 7-methylguanine in a human population at high risk for gastric cancer. A strong correlation was observed between nitrate and N-nitrosoproline excretion (p less than 0.00000); statistically significant correlations (p less than 0.05) were also observed for N-nitrosoproline with 3-methyladenine (p = 0.003) and with 7-methylguanine (p = 0.03) and for 7-methyl-guanine with nitrate (p = 0.02), although these correlations were sensitive to outliers. Smokers appeared to excrete slightly higher levels of 3-methyladenine than nonsmokers; no other difference was observed between smokers and nonsmokers or between drinkers and nondrinkers. The correlation between N-nitrosoproline excretion and nitrate excretion supports the hypothesis that elevated endogenous nitrate levels may contribute to elevated endogenous formation of N-nitroso compounds. PMID- 1855926 TI - Novel, sensitive assays for O6-alkylguanine and its repair and their application to studies of the molecular epidemiology of this lesion in human populations. AB - Two assays suitable for monitoring human populations are presented--one for O6 alkylguanine-type adducts and one for the corresponding repair activity. The assay for adducts is based on competition for repair by O6-alkylguanine-DNA alkyltransferase of lesions in the unknown DNA and in an oligonucleotide containing a single residue of O6-methylguanine (O6-meGua). The assay can reliably detect as little as 0.5 fmol O6-meGua or 3 fmol O6-ethylguanine in 10-15 micrograms DNA, and it has been used to measure O6-meGua (up to approximately 5 x 10(-7) mol/mol guanine) in lymphocyte DNA from individuals receiving procarbazine or dacarbazine. The assay for repair activity utilizes the same oligonucleotide as substrate for the enzyme, in combination with immunoprecipitation for convenient separation of repaired from unrepaired substrate. Examination of repair activity in biopsy specimens of gastric mucosa has revealed a correlation with the corresponding activity in lymphocytes (r = 0.7; p less than 0.01), indicating that lymphocytes could be used as surrogate markers for repair activity in gastric mucosa. PMID- 1855928 TI - Possible effect of infection with liver fluke (Opisthorchis viverrini) on the monitoring of urine by enzyme-linked immunosorbent assay for human exposure to aflatoxins. AB - Several laboratories have initiated studies to assess human exposure to aflatoxin at an individual level by measuring aflatoxin metabolites in the urine by immunoassay. The fact that the antibodies recognize a variety of metabolites, albeit with differing affinities, means that any environmental factor that modifies the pattern of urinary metabolites associated with a given exposure could affect quantification in immunoassay. We have examined two such possible effects: (i) the pattern of metabolites after a dose of 14C-aflatoxin B1 in rats and (ii) the pattern of metabolites in hamsters and humans with and without exposure to liver flukes. We found no dose-related effect on the pattern of urinary metabolites over a 250-fold range, but there was a significant increase in the proportion of water-soluble aflatoxin metabolites in hamsters infected with liver fluke over that in uninfected animals. In human urine samples, there also appeared to be a difference in the metabolites in individuals infected with liver fluke from those in uninfected persons. These observations are relevant to both mechanistic and monitoring aspects of research into aflatoxins. PMID- 1855929 TI - Autopsy and clinical diagnoses in a psychiatric hospital. AB - We made a retrospective analysis of clinical diagnoses and autopsy findings for patients who died in the psychiatric hospital in the city of Zagreb in two different periods--1965-67 and 1985-87. Between these two periods, the autopsy rate decreased from 64 to 31%. The level of clinicopathological discrepancies remained the same, but with the decrease in autopsy rate a problem emerged in the diagnosis of respiratory diseases. The purpose and value of autopsy in a psychiatric hospital is discussed. PMID- 1855930 TI - Use of the autopsy in Northern Ireland and its value in perioperative deaths. AB - A report on the pilot study of the Confidential Enquiry into Perioperative Deaths was published recently in the United Kingdom. The scheme was designed as a specialized form of clinical audit relating to perioperative patient care. Because the report placed little emphasis on autopsy, we have looked at all autopsied perioperative deaths, as defined by the enquiry, over a three-year period (1986-88) in a defined catchment area of Northern Ireland. Class I major discrepancies of diagnosis between clinical and postmortem records were found in 21% of 213 autopsied perioperative deaths. By definition, these represented instances in which an adverse impact on patient survival had resulted from the discrepancy. In an additional 29% of cases, there were Class II major discrepancies, which were discrepancies in the primary diagnosis not relevant to life-saving treatment. In 30% of cases there was a discrepancy in a secondary diagnosis, which might have affected the eventual prognosis, had the patient survived, but which was not related directly to the cause of death; these were termed Class III discrepancies. In 47% of cases, there were Class IV discrepant secondary diagnoses, which were 'incidental' findings and had no bearing on prognosis. To put these findings in context, the autopsy rate in Northern Ireland was 12% in 1987, with a higher rate (23%) in the two main teaching hospitals and a lower rate (8%) in all other hospitals. The rate of coroner's autopsies, 6%, is uniform throughout Northern Ireland. Coroner's autopsies are carried out mostly by the salaried staff of the State Pathologist's department. The observed differences in the rates of hospital autopsies reflect local deficiencies of pathologists in relation to the work load. In a series of consecutive autopsies carried out at one of the main teaching hospitals, the highest autopsy rate (68%) was found for paediatric patients, with rates of 29% for surgical and 23% for medical cases. The proportion of hospital autopsies carried out in perioperative surgical patients was the same as that for medical patients, reflecting the fact that no particular emphasis is placed on use of the autopsy as a form of clinical audit for the perioperative group. PMID- 1855931 TI - Exposure to asbestos in Monfalcone, Italy. A necropsy-based study. AB - The Monfalcone area in north-eastern Italy (total population, about 60,000) is a small industrial district in which shipbuilding is the main industry. We examined thoracic cavities for hyaline pleural plaques and routine lung sections for asbestos bodies in 1765 necropsies performed at Monfalcone Hospital. In 553 cases, we also isolated and quantified asbestos bodies in the lungs (Smith Naylor's method). Occupational histories were obtained from the relatives of 798 patients. The prevalence of pleural plaques was significantly higher (p less than 0.001) among residents of the Monfalcone region (73.6% of men, 26.7% of women) than among nonresidents. Similarly, asbestos bodies were found more frequently in lung sections from residents. A good correlation was observed between pleural plaques and the asbestos body content of the lung (Spearman's correlation coefficient, 0.53). Different occupational groups showed very marked differences in the prevalence of plaques in general, in the prevalence of large plaques and in the numbers of asbestos bodies in the lung. Subjects who had worked in the shipyard or in a sodium carbonate factory had the highest indices. Exposure to asbestos had occurred at work for the large majority of men for whom data on occupation had been collected and through domestic contacts for the large majority of women. In a small portion of cases, environmental exposure could not be excluded as the cause of the objective signs. Pleural plaques, the asbestos body content of the lungs and occupational history must be considered together in monitoring exposure to asbestos in a given geographical area. PMID- 1855932 TI - Autopsy indicators of exposure to asbestos and lung cancer. AB - In many instances, only post-mortem examination can provide probative data about (i) the presence of lung cancer and (ii) its relationship to exposure to asbestos. Moreover, the results of an autopsy may suggest that a thorough investigation of occupational history should be carried out, since such information is rarely recorded in clinical records. We considered pathological indicators for selecting subjects who had a high likelihood of previous occupational exposure to asbestos. The positive predictive value of pleural plaques ranged from 20 to 75%, depending on their size and on the concentrations of asbestos bodies and uncoated mineral fibres in the lung. The probability of no exposure was greater than 90% if neither asbestos bodies nor uncoated mineral fibres were found. Another purpose of our work on lung cancer and exposure to asbestos was to investigate the relationships between exposure and the occurrence of specific cell types of lung cancer in an autopsied population. Both work history and asbestos body count were considered. The matched analysis showed some tendency towards an association between the occurrence of adenocarcinoma and the presence of indicators of exposure to asbestos. PMID- 1855933 TI - The perinatal autopsy: a neglected source of discovery. AB - The perinatal autopsy is frequently viewed by pathologists as being scientifically unrewarding and contributing little to patient care. To emphasize its importance in patient management, genetic counselling and specific research, a ten-year review (1979-88) was made of the perinatal autopsy experience at Loyola University Medical Center. The 657 deaths included late fetal deaths (22%), early neonatal deaths (51%), late neonatal deaths (10%) and deaths between 29 days and one year (17%). Comparison of the principal causes of death in various groups categorized by birth weight and age revealed significant trends. There has been a steady decline in mortality from immediate complications of immaturity, while the mortality rate from long-term complications of immaturity has not increased. There were increased frequencies of congenital diaphragmatic hernia and cardiac malformations, while the frequency of renal malformations decreased; the etiological significance of these changes requires further evaluation. A correlation of clinical observations with post-mortem findings indicates that newer diagnostic procedures, such as ultrasound, echocardiography and cardiac catheterization, are of limited value for accurate diagnosis of complex anomalies, cystic renal disease and chromosomal anomalies. A substudy included cases up to 18 years of age. The frequency of childhood neoplasia was low (17 cases), and among these cases there was a predominance of haematological malignancies (11 cases). Even with these small numbers, a shift in cause of death from disseminated malignancy to overwhelming infection was apparent. This paper includes the essential elements of a protocol for perinatal autopsies, with illustrations of specific applications. The perinatal autopsy is clearly an undervalued source of information and discovery. Little or no information is available from developing countries, where autopsies could provide information on causes of paediatric mortality and permit recognition of disease patterns, which is so critical to the planning of health services. PMID- 1855934 TI - Role of necropsy at neonatal and infantile ages. AB - One of the aims of necropsy at neonatal and infantile ages is to identify the causes of death in this population, which is decreasing continuously because of the decay in natality seen in Italy as well as in other western countries over the last few decades. Analysis of 2410 autopsies performed on 92% of deaths in infants under one year of age occurring at the Bambino Gesu Hospital in Rome in 1974-89 shows a striking change in the principal causes of death in recent decades: Malformations, neonatal anoxia and immaturity have now become the main causes of death in the first year of life, while there is a very low rate of nutritional and infectious diseases, which predominated in the past. The autopsy results obtained indicate, however, that the policy of paediatric care in public health systems must be changed. PMID- 1855935 TI - Pathological findings in perinatal autopsies. PMID- 1855936 TI - Autopsy as the yardstick for diagnosis: an epidemiologist's remarks. PMID- 1855937 TI - Contribution of post-mortem examination to cancer registries. AB - In developed countries, the post-mortem examination may not be critical to the identification of patients with cancer, since diagnostic sophistication and histological verification are readily available. The autopsy should be considered of increasing importance, however, to epidemiologists and other investigators who use the data generated by cancer registries. The contribution of post-mortem examinations to etiological studies, to documentation of the natural history of disease in a changing environment and to evaluating diagnostic and therapeutic modalities should, in fact, be recognized as essential to the practice of modern medicine and to research. In the less developed countries, cancer registration must depend to a much greater degree on necropsy for identification of cancer patients, since surgical biopsy may be limited or selected and often specimens are not even submitted for examination. The primary site and histology of a tumour are frequently not available from clinical records, which may carry significant inaccuracies. Most of the important observations and contributions relating to the geographical pathology of cancer have made substantial use of post-mortem material. All of the investigative approaches that are dependent on reliable cancer registry data and that involve use of information derived from autopsies are equally applicable to developed and less developed countries. Such information is of enormous importance to public health planning, and the potential for disease prevention cannot be overestimated. PMID- 1855939 TI - The role of autopsy in cancer registration in Sweden, with particular reference to findings in Malmo. PMID- 1855938 TI - Contributions of autopsy to population-based cancer epidemiology: targetted intervention to improve ascertainment. AB - The importance of autopsy data in cancer epidemiological investigation is well appreciated by researchers at the Mayo Clinic. The Rochester Epidemiology Program Project is a complete population-based collection of morbidity and mortality data in Olmsted County, Minnesota (population, 100,000), funded by the National Institutes of Health since 1964. Comprehensive ascertainment of cancer in this community cohort has been augmented by initial diagnosis at autopsy for 12% of colorectal cancers, 35% of intracranial neoplasms, 45% of phaeochromocytomas and 37% of renal-cell carcinomas. These rates are in stark contrast to autopsy diagnoses in our cancer registry--usually less than 1%. The difference is attributable to the denominator in these comparisons, a concept of vital importance to the epidemiological interpretation of autopsy findings. Despite the enormous value of the autopsy in our research, social and economic factors diminished autoptic rates in Olmsted County from 63% in 1970 to 39% in 1984. These rates are well above that for the USA as a whole but parallel our national decline in frequency of autopsy. The major factors responsible for this reduction appear to be the increasing proportion of deaths in nursing homes and the advent of declining reimbursement in US health care. PMID- 1855940 TI - Selection for necropsy: evaluation of 321 autopsied cases from 3041 consecutive deaths among residents of a defined geographical area. AB - By undertaking to act as 'medico necroscopo' (the medical doctors in charge of authorizing every burial) in the Unita Socio-Sanitaria Locale (USSL) 70, a region containing 92,500 inhabitants, we were able to collect over a four-year period (1985-88) information on 3371 deaths among residents of the area. Of these, 68.1% died at home, 12.6% in hospital with no autopsy, 9.5% in hospital with an autopsy and 9.8% outside of the USSL region. For the analysis, age, sex and leading cause of death were considered as explanatory variables and place of death and proportion of autopsied cases as the response variables. The factors found to be associated with deaths occurring in hospital were non-neoplastic (particularly cardiovascular and digestive) pathological conditions in patients under the age of 60. People with malignant neoplasms usually died at home, especially when they had a gastric or breast cancer. Factors associated with autopsy were: death at a young age, short length of hospitalization and death from a cardiovascular disease. Sex did not appear to play a direct role in selection for necropsy. Our results indicate that, in our and similar regions, the cases selected for autopsy form a subset that is so specific that any extrapolation to the total deceased population is misleading. PMID- 1855941 TI - Nationwide autopsy registration over 30 years. AB - In this paper, a unique, nationwide autopsy registration system used in Japan is introduced, which has been used by the Japanese Pathological Society since 1958. The autopsy data collected are published annually in an Annual of Pathological Autopsy Cases in Japan, known in Japanese as the Bouken Shuho. In the most recent volume, about 40,000 cases (representing about 5% of all deaths in Japan) were presented. These annual volumes comprise two parts: a description of findings and a statistical section. The latter is composed mainly of tables, including tabulations of disease, age and sex; disease and geographical location; primary site and histological type of cancer; and primary site/primary site for double primary malignant neoplasms. Since 1974, tabulation has been computerized, and this same file is also used to retrieve descriptive data in the book. Since 1984, the findings section of the Bouken Shuho has been published using a desk-top system. A project to incorporate the original documents stored in this system, in order to establish a more sophisticated, fully computerized document retrieval system, is under way. PMID- 1855942 TI - Autopsy rates in medical schools and hospitals in Japan. AB - The autopsy rates in Japanese medical schools and hospitals were reviewed. Although moderate autopsy levels have been maintained in medical schools (50%) and large training hospitals (30%), a slight tendency towards a decrease was demonstrated recently. Since autopsy is important in education, research and the quality control of medicine, it is essential to keep the autopsy rate high. Our analyses indicate that autopsy gives satisfaction to clinicians if clinical data are correlated in detail with pathological findings. Thus, efforts should be directed to strengthening the training of pathologists in the analysis of clinical data, which are essential for correct pathological diagnoses. In order to cope with the rapid progress in all fields of medicine, pathologists must collaborate with clinical staff to obtain all the information necessary for interpretation of autopsy data. This action also helps to keep the autopsy rate high. No international guidelines are available on autopsy. Autopsies are carried out for different purposes at different levels. An internationally agreed set of rules would allow efficient use of autopsy data for epidemiological studies. Genetic analysis of autopsy material is now feasible, and this may be useful in tracing etiological factors, such as infections and genetic predisposition. Various aspects of autopsy must be reconsidered in the light of modern science. PMID- 1855943 TI - The role of autopsy in the control of mortality in Austria. AB - Maintenance of an acceptable autopsy rate is important for continuous quality control of the mortality statistics of a population, as well as for continuous quality control of clinical diagnosis in general. A high autopsy rate is of particularly great value for maintaining the quality of data on mortality from neoplastic diseases and, by feed-back, for ensuring the quality and accuracy of clinical diagnosis of malignant neoplastic diseases. PMID- 1855944 TI - Latent malignancies at autopsy: a little used source of information on cancer biology. AB - Latent carcinomas, found incidentally at autopsy, are defined, and information about such tumours in the prostate, adrenal gland, kidney and thyroid is reviewed. A previously unsuspected carcinoma of the prostate was found in 350 of 1327 (26.4%) autopsies performed in seven countries on men over 45 years of age. The prevalence of latent carcinoma of the prostate at autopsy was greater in older men and in areas of higher incidence and/or mortality, as for clinical carcinomas. Neuroblastomas of the adrenal gland have been reported at a rate of 1:39 in newborn infants who died of other causes; this rate is comparable to that of latent prostatic carcinoma. Neuroblastomas are not found in the adrenal glands of infants older than three months, indicating that the body has a method for destroying them. Latent carcinomas are also found in the thyroid gland at autopsy, at rates ranging from 10 to 30%. The age and area differences seen for prostatic carcinoma do not appear to be operative for these tumours; moreover, latent carcinomas are found more frequently in males, whereas the clinical disease is twice as frequent in females. More research should be carried out to elucidate the differences between people who develop clinical carcinoma, those who have a latent carcinoma 'under control' and those who have neither. PMID- 1855945 TI - Correlation of early pathological lesions in the bronchial tree with environmental exposures: study objectives and preliminary findings. AB - Lung specimens were taken at autopsy from 214 subjects aged 35 years and over who had died from nonpulmonary causes in Athens or the surrounding countryside. The samples were coded and examined for entities thought to be linked to environmental exposures, reflecting epithelial, possibly precancerous, lesions, as well as for morphological features, which were summarized using Reid's index. Of the 214 specimens, 142 were suitable for pathological examination. Next-of-kin of 101 of the dead people were identified and asked about the subject's exposure to active smoking, passive smoking, possible occupational hazards, dietary factors and proxy indicators of air pollution (residence). Preliminary analysis, controlling for age and sex, indicates that active smoking is related, although not statistically significantly, to both the Reid index (difference, 0.28, corresponding to a one-tailed p value of 0.07) and epithelial, possibly precancerous lesions (difference, 16.7, corresponding to a one-tailed p value of 0.09). Nonsignificant differences were found in the preliminary analysis of this ongoing study with respect to the other environmental factors examined. PMID- 1855947 TI - Autopsy in epidemiology and medical research. PMID- 1855946 TI - Changes in underlying causes of death during 85 years of autopsy practice in Trieste. AB - In 1901, 20% of autopsied subjects in Trieste were under the age of 30 and 28.8% were over 70. By 1985, only 0.2% were under 30 years of age and 74.5% over 70. An analysis of autopsy reports for 1901 reveals that the primary causes of death at that time were tuberculosis (22.4%), acute pulmonary infections (13.7%) and malignant neoplasms (10.6%). Other pathological conditions found at autopsy were infectious lesions (10.4%), chronic obstructive pulmonary disease (10.2%), arteriosclerosis (only 6.4%), syphilis (4.7%), nutritional deficiency (4.7%), cirrhosis of the liver (4.6%) and acute infections (1.1%). Overall, infectious diseases accounted for 55% of deaths in 1901. In 1985, the cause of death was infection in only 3.7% of cases. During the period analysed, the percentage of deaths from cancer tripled and mean length of survival increased by more than 20 years. In 1901, the neoplasms found most frequently were gastric cancer in males (17.9%) and cancers of the uterus and ovary in females (both 13%). Lung cancer accounted for 7.7% of all deaths from malignant neoplasms in males, and breast cancer for 10.8% of such deaths among females. By 1985, lung cancer accounted for 32.4% of deaths from malignant neoplasms among males and breast cancer for 18% among females. Between 1901 and 1985, there were highly significant increases in the numbers of deaths due to arteriosclerosis and to malignant neoplasms in people of each sex. PMID- 1855948 TI - Occurrence of liver cirrhosis among autopsies in Trieste. AB - The reports of 26,879 autopsies performed at the Institute of Pathological Anatomy at the University of Trieste during 1876-85 (70% of all deaths that occurred in the Province) were examined, and 2563 cases of liver cirrhosis were found. Analysis of the sample allowed us to make the following conclusions: (i) The prevalence of cirrhosis at autopsy is high in Trieste and shows no tendency to decrease, as has been inferred by some clinical studies. (ii) The increasing average age at death over the decade studied appears to be unrelated to the new, early treatments adopted for hepatopathic patients, since a similar yearly increase in mean age at death was seen for the whole population of the Province. The combination of a high incidence of cirrhosis and increasing average age of patients will probably result in an increasing occurrence of hepatocellular carcinoma. (iii) The observed male:female ratio (2.3) is analogous to that of alcohol drinkers in the Province and thus suggests a role of alcohol abuse in the development of cirrhosis. The distribution of markers of hepatitis B virus in the population of Trieste, which is very similar in the two sexes, supports this hypothesis. PMID- 1855949 TI - Comparison between diagnoses of cancers of the stomach, colon, rectum, gall bladder, liver and pancreas on death certificates and at autopsy in Trieste, 1970 84. PMID- 1855950 TI - Comparison of diagnoses of cancers of the respiratory system on death certificates and at autopsy. PMID- 1855951 TI - Comparison between diagnoses on death certificates and autopsy reports in Trieste: gynaecological cancers. AB - We have compared autopsy results with the diagnosis reported on 759 death certificates for gynaecological cancers. High levels of discrepancies were noted for all sites. Surprisingly, complete agreement between death certificates and autopsy reports was found for only 30% of cervical and corpus tumours and for 50% of ovarian tumours. This low level of agreement was due partly to the poor quality of death certificates of older women. No difference in accuracy was found over the 15-year period considered. The most obvious causes of the discrepancies were of two types. The first was erroneous interpretation of codes; confusion between 180 (cervix) and 182 (corpus) was very frequent. The second type was associated with clinical factors, such as confusion of anatomical site, adjacent organs or metastases being diagnosed as primary tumours. A relatively frequent cause of inaccuracy on death certificates was consideration of patients who had been cured of a cancer as having died of the disease. PMID- 1855952 TI - The role of the autopsy in assessing clinical diagnoses. PMID- 1855953 TI - Autopsy diagnosis versus clinical diagnosis, particularly in malignant disease. Comparison of two periods: 1961-70 and 1978-87. AB - We present a comparison of autopsy records in the Institute of Pathology of Munster University during 1961-70 with those from 1978-87. The study was based on 11,716 autopsy cases in which reliable documentation of clinical diagnosis could be adequately correlated and compared with the respective autopsy diagnoses. In the decade 1961-70, 34% of the clinical diagnoses were correct, 15% were nearly correct and 23%, incorrect (24% had to be supplemented without relevance to therapy or prognosis, 4% side diagnoses). In the decade 1978-87, 50% of the clinical diagnoses were correct, 15% nearly correct and 18% incorrect (17% supplemented). With respect to malignant tumours, in 1961-70 clinical diagnoses were correct in 37% of cases and incorrect for 26%; in 1978-87, 47% were correct and 15% incorrect. This comparison covered all major tumour locations. The difference in incorrect clinical diagnoses between the two periods is statistically significant. With respect to infectious diseases, the concordance between clinical and autopsy diagnoses is even poorer. Lues (syphilis) is now rarely recognized in clinical diagnoses, even though it may be fatal; 50% of tuberculosis patients die from miliary tuberculosis without a correct diagnosis. Endocarditis in all its forms was underdiagnosed clinically in 75% of cases. These data provide substantial arguments in favour of autopsy control of clinical diagnosis, also including histological findings in biopsy specimens. PMID- 1855954 TI - Autopsy: clinicopathological concordance and imaging techniques. AB - We have assessed clinical and post-mortem diagnostic agreement, comparing two one year periods 10 years apart (1976 and 1986), in order to evaluate the contribution of noninvasive imaging techniques to diagnostic accuracy. Excluding stillbirths, perinatal deaths and forensic cases, a total of 434 hospital autopsies were analysed retrospectively, 190 from 1976 and 244 from 1986. The overall percentage of major disagreement between clinicians and pathologists was 55% for autopsies carried out in 1976 and 34% for those in 1986. In the majority of these, the clinicians located the immediate cause of death outside the organ system identified by the pathologist. For major conditions not classified as the immediate cause of death, the concordance rates were 62% in 1976 and 75% in 1986; this significant improvement between the two periods suggests that the new modalities in widespread use in 1986 may have increased clinical diagnostic accuracy with respect to these conditions. We conclude that (i) the rate of verification at autopsy of the clinically suspected cause of death remains unacceptably low; (ii) the autopsy is indispensable as an instrument of quality control and for generating mortality and morbidity statistics; and (iii) the introduction of new diagnostic modalities seems not to have improved the accuracy of clinical diagnosis of the immediate cause of death but may significantly have improved the detection of other major diseases. PMID- 1855955 TI - Correlation of clinical diagnosis with autopsy findings. AB - We investigated 110 cases, selected at random out of the total of 1876 autopsies performed in the Institute of Pathological Anatomy and Histology at the University of Ferrara-Arcispedale Santa Anna on patients who had died at the hospital during 1983-87. Clinical data were taken from 'necropsy request forms' filled in by clinicians and from medical records. We then evaluated the extent of agreement and disagreement, expressed as underdiagnosis (false-negative) and overdiagnosis (false-positive), between the clinical and pathological records with regard to primary disease and to cause of death. Agreement between the diagnoses was 81% for primary disease and 58% for cause of death. The diagnoses of neoplastic, cerebrovascular and cardiovascular diseases showed the closest agreement. Among the neoplasms, those of the liver, gall-bladder, pancreas, retroperitoneal space and prostate were most often overlooked in clinical diagnoses. We had conflicting results for cancer of the lung and of the colon rectum, for which there was a high level of agreement, but also a large number of false-positive cases and cases in which they were found by chance at autopsy. For cerebrovascular diseases, false-negative and false-positive diagnoses were seen most often for cause of death. With regard to cardiovascular diseases, a relatively uniform distribution was found for myocardial infarction among the three categories, and a high rate of agreement was found for pulmonary embolism. Of all diseases, bronchopneumonia was associated with the highest percentage of false-negative diagnoses for cause of death. Our data on digestive diseases show the strongest agreement on diagnosis of primary disease in relation to cirrhosis of the liver; a high rate of agreement on cause of death was confirmed for alimentary bleeding. Active tuberculosis was detected only at autopsy. We conclude that autopsy is a valid tool for investigation, despite the availability of sophisticated diagnostic techniques. PMID- 1855956 TI - [Fabrication of a unit implant prosthesis. Combined implant surgery and guided tissue regeneration at an extraction site]. PMID- 1855957 TI - [The dental assistant and the first appointment]. PMID- 1855958 TI - [Agenesis of upper lateral incisors treated with unit implants]. PMID- 1855960 TI - [Bleaching of vital teeth. Part one of a comparative study of two ambulatory methods]. PMID- 1855959 TI - [Dentistry and public health. Description of the dental status of a population. Need for care and care provided]. PMID- 1855962 TI - [Original design for a new operatory]. PMID- 1855961 TI - [Esthetic rhinoplasty. A difficult but fascinating operation]. PMID- 1855963 TI - [Study of ceramics for ceramometal prostheses. Original fabrication of models for their characterization]. PMID- 1855964 TI - [A case of gemination of two central incisors]. PMID- 1855965 TI - [A plan for dental care in El Salvador]. PMID- 1855966 TI - [High frequency sounds. Their adverse effects on the dentist's inner ear]. PMID- 1855967 TI - [The development of orthodontics from yesterday to tomorrow]. PMID- 1855968 TI - [Recovering of two gingival recessions. Submerged connective graft and coronally repositioned flap]. PMID- 1855969 TI - [Comparison of analgesic activity of mefenamic acid and paracetamol in treatment of pain after extraction of impacted lower 3d molar]. PMID- 1855970 TI - [DMF in 1990]. PMID- 1855971 TI - [Three "dental kits" by Grangeret, "Cutler to the Emperor". The instrument case of Napoleon's dentist, the enigma of his will]. PMID- 1855972 TI - Cloning, genetic analysis, and nucleotide sequence of a determinant coding for a 19-kilodalton peptidoglycan-associated protein (Ppl) of Legionella pneumophila. AB - A genomic library of Legionella pneumophila, the causative agent of Legionnaires disease in humans, was constructed in Escherichia coli K-12, and the recombinant clones were screened by immuno-colony blots with an antiserum raised against heat killed L. pneumophila. Twenty-three clones coding for a Legionella-specific protein of 19 kDa were isolated. The 19-kDa protein, which represents an outer membrane protein, was found to be associated with the peptidoglycan layer both in L. pneumophila and in the recombinant E. coli clones. This was shown by electrophoresis and Western immunoblot analysis of bacterial cell membrane fractions with a monospecific polyclonal 19-kDa protein-specific antiserum. The protein was termed peptidoglycan-associated protein of L. pneumophila (Ppl). The corresponding genetic determinant, ppl, was subcloned on a 1.8-kb ClaI fragment. DNA sequence studies revealed that two open reading frames, pplA and pplB, coding for putative proteins of 18.9 and 16.8 kDa, respectively, were located on the ClaI fragment. Exonuclease III digestion studies confirmed that pplA is the gene coding for the peptidoglycan-associated 19-kDa protein of L. pneumophila. The amino acid sequence of PplA exhibits a high degree of homology to the sequences of the Pal lipoproteins of E. coli K-12 and Haemophilus influenzae. PMID- 1855973 TI - Borreliacidal activity of sera from hamsters infected with the Lyme disease spirochete. AB - An in vitro borreliacidal assay that accurately reflects the levels of protective antibody determined by passive transfer of immunity studies was developed. Borreliacidal antibody in sera obtained from normal hamsters infected with Borrelia burgdorferi was readily detected. When immune serum containing complement was incubated with B. burgdorferi organisms, spirochetes were killed within 2 h. Treating immune serum with anti-hamster immunoglobulin G abrogated the borreliacidal activity. Killing of B. burgdorferi in serum was detected 1 week after infection; it peaked at week 3 and gradually declined. Relatively high levels of borreliacidal antibody were found, especially in week 3 immune serum, which could be diluted 1,280-fold. The decrease in borreliacidal antibody after infection may account for occurrences of reinfection and the remitting course of Lyme disease. PMID- 1855974 TI - Role of host cellular response in differential susceptibility of nonimmunized BALB/c mice to Plasmodium berghei and Plasmodium yoelii sporozoites. AB - We found BALB/c mice to be on the order of 2,000 times more susceptible to Plasmodium yoelii than Plasmodium berghei sporozoites, as measured by the ability of these sporozoites to differentiate into microscopically detectable hepatic schizonts in the livers of immunologically naive mice. One of the factors that determine the relative insusceptibility of mice to P. berghei sporozoites is the innate cellular inflammatory response that the mice mount after injection with sporozoites. The cellular inflammatory response against P. berghei is initiated soon after sporozoite injection; by 24 h, substantial histopathological changes have developed within the liver. There is considerably less of a cellular inflammatory response against P. yoelii; significant histopathological changes within the liver are not observed until well after hepatic schizonts have begun to rupture at around 44 h postinjection of sporozoites. These differences in the cellular inflammatory response against two different, closely related species of sporozoites are of considerable interest. The data strongly suggest that the BALB/c-P. berghei sporozoite system is a relatively poor biological model for sporozoite immunization studies. PMID- 1855975 TI - Anticandidal activity of major human salivary histatins. AB - We have previously shown that histatins 1, 3, and 5 are homologous, histidine rich proteins present in human parotid and submandibular secretions which contain 38, 32, and 24 amino acids, respectively. Interest in these proteins stems from the fact that histatins exhibit candidacidal and candidastatic activities. The goal of the present investigation was a detailed functional characterization of these anticandidal activities of histatins at the levels of killing of blastoconidia, killing of germinated cells, and inhibition of germination by using three bioassays. Candidacidal activities were evaluated at several ionic strengths, in the presence of different mono- and divalent ions, and at multiple pH values. In addition, the susceptibility of Candida albicans in different growth phases to histatins was investigated. While all three major human histatins demonstrated candidacidal activities, they differed in their abilities to kill blastoconidia and germinated cells, with histatin 5 being the most active, histatin 3 showing moderate activity, and histatin 1 exhibiting the lowest level of activity. For the inhibition of germination, however, histatin 3 exhibited more activity than either histatin 1 or histatin 5. The candidacidal activity of histatins was inversely proportional to both the ionic strength and the divalent cation concentration in the medium. Stepwise reduction of the pH of the assay medium enhanced the candidacidal activities of histatins 1 and 3, while the activity of histatin 5 was pH independent over the range of pHs 4 to 8. C. albicans in log-phase growth was more susceptible to histatins 1 and 3 than cells in stationary phase. Cells in either growth phase were still more vulnerable to histatin 5 than to histatins 1 and 3. The results obtained establish the functional relationship of the major histatins with respect to both their fungicidal and fungistatic activities and provide insights into their activities under ionic and pH conditions likely to be encountered in vivo in the oral cavity. Moreover, the data point towards possible mechanisms responsible for the anticandidal activities of histatins. PMID- 1855976 TI - Identification of Campylobacter jejuni and Campylobacter coli antigens with mucosal and systemic antibodies. AB - The development of a rapid and specific diagnostic assay for Campylobacter infections is important in determining the etiology of acute diarrhea in humans. Studies have shown that sonicated whole bacteria or partially purified antigens cross-reacted with antibodies against other closely related bacteria. To solve the problems of specificity, we identified specific antigens of Campylobacter jejuni and Campylobacter coli for use in diagnostic assays. We investigated the responses of serum, urine, and intestinal lavage antibodies in infected (fed live bacteria) and parenterally immunized (intraperitoneal injection of sonicated whole bacteria with adjuvant) mice directed against C. jejuni or C. coli by Western blot (immunoblot) analysis. Antibody responses were examined weekly for up to 28 days. Fewer antigens were detected by urinary and intestinal lavage fluid immunoglobulin A (IgA) than serum IgG and IgM for both parenterally immunized and infected mice. Serum from parenterally immunized mice detected more antigens than that from infected mice. Two high-molecular-weight antigens (62,000 and 43,000) were predominantly detected by serum, urine, and intestinal lavage fluids of both parenterally immunized and infected mice. Serum antibodies from 28 day parenterally immunized mice detected one antigen specific to C. coli with a molecular weight of 38,000 and one antigen specific to C. jejuni with a molecular weight of 27,000. An immunodominant protein with a molecular weight of 31,000 common to both C. jejuni and C. coli was also recognized by serum antibodies from parenterally immunized mice. PMID- 1855977 TI - Role of neutrophil receptors in opsonophagocytosis of coagulase-negative staphylococci. AB - The role of neutrophil complement receptors in the opsonophagocytosis of 10 strains of coagulase-negative staphylococci was investigated. Polymorphonuclear leukocytes from adults as well as term and premature newborn infants were tested with normal human serum, adult hypogammaglobulinemic serum, and pooled premature infant serum in an opsonophagocytic assay. Neutrophils from premature infants demonstrated significantly lower killing capacity (62%) than neutrophils from adults (86%) or term infants (84%; P less than 0.02). Maximum inhibition of opsonophagocytosis by adult or infant neutrophils occurred with an FcIII receptor blockade (80%), whereas a blockade of complement receptors produced minimal inhibition. Opsonophagocytic activity for the coagulase-negative staphylococci was not influenced by the serum source but was influenced by reducing the serum concentration below 5%. Abrogation of the complement activity of normal human serum by heating or the addition of ethylenediamine tetraacetate reduced opsonophagocytosis by 100 and 96%, respectively, whereas selective inhibition of the classical complement pathway reduced opsonophagocytosis by only 40%. Thus, opsonophagocytosis of coagulase-negative staphylococci by human sera appears to be mediated primarily by neutrophil Fc receptors, but complement is also required. The inefficiency of these interactions with neutrophils from premature infants may partially explain the enhanced susceptibility of very-low-birth weight neonates to disseminated, coagulase-negative staphylococcal infections. PMID- 1855978 TI - The 18-kilodalton antigen secreted by Aspergillus fumigatus. AB - One of the major antigens secreted in vitro by Aspergillus fumigatus is an 18-kDa basic protein which has been purified by cation-exchange chromatography. It is recognized by sera from aspergilloma patients. It is also the major circulating antigen found in urine of patients with invasive aspergillosis. Our results indicated that this antigen has potential for the diagnosis of both aspergilloma and invasive aspergillosis. PMID- 1855979 TI - Role of lipooligosaccharides in experimental dermal lesions caused by Haemophilus ducreyi. AB - The mouse and rabbit intradermal injection models have been used to define factors that may be important in Haemophilus ducreyi pathogenesis. We used H. ducreyi strains with diverse geographic origins and phenotypic characteristics to evaluate the experimental models. Injection of live and heat-killed bacteria caused skin abscesses in both models. Semiquantitative cultures of skin injected with live bacteria showed that H. ducreyi failed to replicate in animal tissue. These data suggested that the experimental lesions were caused by a heat-stable substance such as lipooligosaccharide (LOS). In mice, injection of H. ducreyi and Haemophilus influenzae LOS and Escherichia coli lipopolysaccharide caused mild to moderate inflammation. In rabbits, injection of H. ducreyi LOS caused intradermal abscesses that were histologically similar to those caused by live and heat killed bacteria. H. ducreyi and Neisseria gonorrhoeae LOS caused significantly larger lesions than equivalent amounts of H. influenzae LOS and E. coli lipopolysaccharide in the rabbit model. We conclude that the intradermal injection models are not valid models to study the growth of H. ducreyi in vivo. However, these data indicate that H. ducreyi LOS may play an important role in the pathogenesis of chancroid and that the rabbit model should be useful in studying H. ducreyi LOS toxicity at the cellular level. PMID- 1855980 TI - Experimental elimination of tumor necrosis factor in low-dose endotoxin models has variable effects on survival. AB - Tumor necrosis factor alpha (TNF) is thought to play a major role in the pathogenesis of septic shock. Anti-TNF antibody was preadministered in low-dose endotoxin lethality models in which BALB/c mice were challenged with small amounts of lipopolysaccharide following their sensitization with either carrageenan (CAR) or D-galactosamine (D-GalN). Although the antibody virtually eliminated circulating TNF in both the CAR and the D-GalN models, only the D-GalN model mice were afforded survival, adding to a growing body of evidence that substances other than TNF play a key role in endotoxin-induced lethality. Further examination of sera from these mice showed a much greater elevation of interleukin-6 levels in the CAR-sensitized group than in the D-GalN-sensitized group. PMID- 1855981 TI - Experimental Staphylococcus aureus arthritis in mice. AB - Staphylococcus aureus arthritis is usually caused by bacteremia and is highly destructive. Controlled studies on septic arthritis in humans are difficult to perform, because the time of onset of the infection is unknown. Animal models of bacterial arthritis make it possible to control important variables in experimental studies. We present a mouse model of S. aureus arthritis in which the intravenous administration of 10(7) cells of S. aureus LS-1 induced arthritis or osteitis or both within 3 weeks in 80 to 90% of the mice. Signs of arthritis emerged within the first few days after the injection. An interesting finding was that the S. aureus strain used in this study binds bone sialoprotein, a glycoprotein known to be specifically localized to bone tissue. This new model of S. aureus arthritis enables the study of the kinetics of joint destruction and the host-bacterium relationship as well as therapeutical approaches to septic arthritis and osteomyelitis. PMID- 1855982 TI - Neutralization of Chlamydia trachomatis: kinetics and stoichiometry. AB - Monoclonal antibodies to the major outer membrane protein of Chlamydia trachomatis were used to neutralize C. trachomatis infectivity in HeLa 229 cells and to determine the kinetics and stoichiometry of the reaction. In vitro neutralization of C. trachomatis infectivity proceeded as a first-order reaction and required an activation energy of approximately 20 kcal/mol (ca. 84 kJ/mol). The rate of neutralization was linear with respect to antibody concentration and reaction temperature. The efficiency of neutralization decreased exponentially as the ratio of noninfective to infective chlamydiae increased in the antigen preparation. The neutralization assay was also significantly affected by reaction parameters such as the reaction volume and the duration of incubation. Stoichiometric calculations showed that an average ratio of 10(3) and 10(4) immunoglobulin molecules per chlamydial particle was required to yield 50% neutralization by monoclonal antibodies specifying serovar-specific and species specific epitopes, respectively. The implications of these findings for vaccine design and for the role of the major outer membrane protein in the pathogenesis of chlamydial infections are discussed. PMID- 1855983 TI - Lipopolysaccharidelike immunological properties of cell wall glycoproteins isolated from Cytophaga johnsonae. AB - Glycoproteins (GP) previously shown to be involved in the gliding motility of Cytophaga johnsonae were examined for biological activities characteristic of lipopolysaccharide (LPS). These integral membrane proteins activated 70Z/3 pre-B cells to synthesize immunoglobulin M, induced B cells to synthesize non-antigen specific polyclonal immunoglobulin, induced macrophages to produce tumor necrosis factor, and modulated the antibody response to type III pneumococcal polysaccharide in the absence of thymus-derived (T) lymphocytes. Except for the GP activity in the 70Z/3 assay, all activities of the GP were comparable to or greater than those of LPS. No LPS was detected in the preparations of GP used or in the phenol-water extracts of C. johnsonae. The mechanism by which these GP exerted their biological activities was distinct from that of LPS, since LPS resistant C3H/HeJ mice responded to GP. Furthermore, biologically inactive diphosphoryl lipid A obtained from nontoxic LPS of Rhodopseudomonas sphaeroides (an analog of toxic lipid A), which is an antagonist of LPS, did not block the induction of tumor necrosis factor by GP in macrophages. These results showed that the cell surface GP from C. johnsonae are potent LPS-like activators of B cells and macrophages. We suggest that these GP might be good candidates for use in developing an effective adjuvant system. PMID- 1855984 TI - Phenotypic diversity in the alpha C protein of group B streptococci. AB - Group B streptococci (GBS) is the leading cause of neonatal sepsis and meningitis. C proteins are an immunologically important group of surface associated antigens in GBS that remain incompletely characterized. Two C proteins have been designated alpha and beta on the basis of protease susceptibility. We recently used a monoclonal antibody to describe a protective epitope of the GBS alpha (or trypsin-resistant) C protein in the prototype Ia/c GBS strain. In the present study, we examined 51 GBS isolates for expression of C-protein alpha and beta antigens. The alpha antigen, as detected with monoclonal antibody in sodium dodecyl sulfate (SDS) extracts, appears as a heterogeneous series of proteins spaced 8 kDa apart on SDS-polyacrylamide gel electrophoresis, but has a maximum molecular mass that varies among strains from 62.5 to 167 kDa. By immunoblotting with human immunoglobulin A, polyclonal antiserum, or monoclonal antibody, the beta antigen, in contrast, appears as a single protein of molecular mass between 124 and 134 kDa. The amount of alpha antigen expressed by each strain was quantified by enzyme immunoassay inhibition and was found to vary markedly from strain to strain. The susceptibility of strains of GBS to opsonization and killing by human polymorphonuclear leukocytes in the presence of either complement alone or complement with alpha-specific monoclonal antibody was examined. Strains expressing the alpha antigen were less readily killed in the absence of specific antibody than were alpha-negative strains. Killing in the presence of alpha-specific monoclonal antibody was found to correlate directly with the maximum molecular mass of the alpha antigen and with the quantity of antigen on the bacterial cell surface. Isolates of GBS that express the alpha C protein vary widely in the quantity and molecular mass of the alpha antigen produced, and this heterogeneity appears to have biologic importance. PMID- 1855985 TI - Pathogen-related spirochetes identified within gingival tissue from patients with acute necrotizing ulcerative gingivitis. AB - The purpose of this investigation was to determine whether monoclonal antibodies against pathogen-restricted antigens of Treponema pallidum subsp. pallidum could be used as probes for spirochetes in diseased gingival tissue from subjects with acute necrotizing ulcerative gingivitis. A biotin-streptavidin system was used to identify spirochetes bound by monoclonal antibodies in cryostat sections of tissue. Twelve of 16 tissue samples from diseased sites, but none of 8 tissue specimens from healthy sites, reacted with pathogen-restricted antibodies. Organisms were found in intact epithelium and connective tissues adjacent to ulcers. Staining intensity was often high in perivascular locations and around vesicular spaces. Monoclonal antibodies to Bacteroides gingivalis and Treponema denticola were each reactive with diseased gingival tissues, but staining was usually restricted to ulcerated areas. These studies extend recent observations that showed that subjects with acute necrotizing ulcerative gingivitis had both pathogen-related spirochetes in dental plaque and serum immunoglobulin G to pathogen-restricted antigens on T. pallidum subspecies, suggesting that pathogen related spirochetes may be associated with the pathogenesis of certain periodontal diseases. PMID- 1855986 TI - Effect of a factor released by K562 malignant cells in culture on human neutrophil bactericidal activity. AB - We have previously demonstrated that k562 malignant cells in culture contain and release a low-molecular-mass (8-kDa) factor that inhibits adherence-related functions of neutrophils but does not alter fMet-Leu-Phe- or phorbol ester induced oxidative burst (M. Amar, N. Amit, T. Pham Huu, S. Chollet-Martin, M.T. Labro, M.A. Gougerot-Pocidalo, and J. Hakim, J. Immunol. 144:4749-4756, 1990). In this study, we investigated the effects of this factor, referred to as inhibitory factor 1 (IF1), on the bactericidal activity of human polymorphonuclear cells (PMNs) on Staphylococcus aureus opsonized in various ways. S. aureus was used either nonopsonized or opsonized with heat-inactivated serum or normal serum containing complement factors. The bactericidal activity of PMNs preincubated with IF1-treated or control medium was examined by counting the surviving bacteria. The ability of IF1-treated PMNs to kill bacteria was diminished when they were opsonized with normal serum. When S. aureus was not opsonized or was opsonized with heat-inactivated serum, the bactericidal activity of IF1-treated PMNs was similar to that of controls. Likewise, the phagocytosis of IF1-treated PMNs was diminished when S. aureus was opsonized with normal serum but was not altered when S. aureus was not opsonized or was opsonized with heat-inactivated serum. These results suggest that the decrease in killing might be due to defective ingestion. The chemiluminescence response of IF1-treated PMNs was inhibited when S. aureus was not opsonized or was opsonized with normal serum. No effect on chemiluminescence was observed when S. aureus was opsonized with heat inactivated serum. These results suggest that IF1 interferes not only with S. aureus stimulation of PMNs via complement receptors but also with oxygen dependent bactericidal activity. PMID- 1855987 TI - Sequence and structural analysis of surface protein antigen I/II (SpaA) of Streptococcus sobrinus. AB - Streptococcal antigen I/II or the surface protein antigen A (SpaA) of Streptococcus sobrinus is an adhesin which mediates binding of the organism to tooth surfaces. The complete sequence of the gene which encodes SpaA has been determined. The gene consists of 4,584 bp and encodes a protein of 1,528 amino acid residues. The deduced amino acid sequence shows extensive homology with those of the cell surface adhesins from Streptococcus mutans serotypes c and f and from Streptococcus sanguis. Structural analysis of the N-terminal region (residues 50 to 550), which is rich in alanine and includes four tandem repeats of an 82-residue sequence, suggests that it adopts an alpha-helical coiled-coil conformation. Cell surface hydrophobicity may be associated with this region. The C-terminal region is more conserved and includes two tandem repeats of a 39 residue proline-rich sequence. A further proline-rich sequence in this region is predicted to span the cell wall. Although a hydrophobic sequence is present in the C-terminal region, it appears to be too short to span the cell membrane. Anchoring of SpaA in the cell membrane may therefore require some form of posttranslational modification or association with another membrane protein. PMID- 1855988 TI - Conservation of the gene encoding streptococcal antigen I/II in oral streptococci. AB - The spaP gene of Streptococcus mutans serotype c encodes a major cell surface protein, streptococcal antigen (SA) I/II, with an Mr of 185,000, that is thought to be involved in bacterial adhesion to teeth. Proteins with significant amino acid sequence homology to SA I/II have also been found in S. sobrinus and S. sanguis. The objectives of this study were to investigate the conservation of the spaP gene in the mutans groups of streptococci and to determine whether homologous genes were present in other species of alpha-hemolytic streptococci. DNA extracted from representative strains of 19 streptococcal species was examined by Southern hybridization and partial DNA sequence analysis. A series of five overlapping DNA probes from the spaP gene were amplified by the polymerase chain reaction and used in the Southern hybridizations. The entire gene was found to be well conserved in all strains of S. mutans serotypes c, e, and f investigated. A probe from the 3' region of the gene, which encodes residues 857 to 1207 of the SA I/II protein, hybridized with DNA from a number of mutans streptococci, as well as with DNA from nonmutans alpha-hemolytic streptococci. Conservation within this region was further demonstrated by sequencing gene fragments of two strains of S. intermedius and S. oralis. The results show that some regions of the spaP gene are highly conserved not only in the mutans group of streptococci but also in other nonmutans alpha-hemolytic streptococci. This suggests that a family of cell surface proteins which, by analogy with the 185,000-Mr SA I/II of S. mutans, could be involved in bacterial adhesion might exist. PMID- 1855989 TI - Evidence for invasion of a human oral cell line by Actinobacillus actinomycetemcomitans. AB - Actinobacillus actinomycetemcomitans, an oral bacterial species associated with periodontal disease, was found to invade human cell lines. Invasion was demonstrated by recovery of viable organisms from gentamicin-treated KB cell monolayers and by light and electron microscopy. Internalization occurred through a cytochalasin D-sensitive process. Invasion efficiencies of some A. actinomycetemcomitans strains were comparable to those of invasive members of the family Enterobacteriaceae. Differences in invasiveness were correlated with bacterial colonial morphology. Smooth variants invaded more proficiently than rough variants. A. actinomycetemcomitans can undergo a smooth-to-rough colonial morphology shift which results in the loss of invasiveness. Coordinated regulation of genes involved in the rough-to-smooth phenotypic transitions may play a role in the episodic nature of periodontal disease. PMID- 1855990 TI - Roles of motility and flagellar structure in pathogenicity of Vibrio cholerae: analysis of motility mutants in three animal models. AB - Wild-type Vibrio cholerae of both El Tor and classical biotypes (strains N16961 and 395, respectively) and nonmotile mutant derivatives with and without flagellar structures were characterized in three different animal models: (i) the rabbit ileal loop, (ii) the removable intestinal tie adult rabbit diarrhea (RITARD) model, and (iii) the suckling mouse model. Both the wild-type strains and nonmotile mutants were toxinogenic in the rabbit ileal loop and the suckling mouse models. However, all of the nonmotile mutants produced significantly less fluid accumulation than did the wild-type parental strains. The two nonmotile mutants of strain N16961 did not adhere to rabbit ileal mucosa, but both nonmotile mutants derived from strain 395 exhibited adherence. In the RITARD model, the motile El Tor strains were more virulent than both the flagellate and aflagellate nonmotile mutants (all infected rabbits died within 18 h), while the nonmotile mutants, when fatalities occurred, required 78 to 105 h to produce a fatal outcome. Likewise, the motile classical parent 395 produced a fatal outcome within ca. 25 h, while nonmotile mutants required 69 to 96 h. The nonmotile flagellate strain KR31 was not significantly more virulent than the nonmotile aflagellate strain KR26. Of the two classical nonmotile mutants, KR1, which produces a coreless sheathlike structure, was clearly more virulent (5 of 10 rabbits died within 96 h), while KR3 (nonmotile, aflagellate) did not produce fatalities in any of the 10 rabbits tested. Similarly, no significant difference in diarrheagenicity or colonizing ability was detected between the two nonmotile mutants derived from the El Tor strain, but the classical nonmotile mutant with the coreless sheath caused significantly greater diarrhea and colonized for a longer time than did the isogenic nonmotile aflagellate strain, KR3. No significant differences between the nonmotile mutants were detected in competition studies done with suckling mice. Analysis of the wild-type and mutant strains in these three animal models clearly demonstrated a role for motility in V. cholerae pathogenicity, while analysis of only the nonmotile mutants derived from the classical parent suggested a role for flagellar structures. PMID- 1855991 TI - Immunogenicity of Streptococcus pneumoniae type 14 capsular polysaccharide: influence of carriers and adjuvants on isotype distribution. AB - This project investigated the effects of novel carriers and adjuvants on the isotype of murine immunoglobulin G (IgG) antibody to pneumococcal capsular polysaccharide type 14 (S14PS). S14PS conjugated to bovine serum albumin induced a weak antibody response which was 100% IgG1 following injection without adjuvant. The same polysaccharide conjugated to flagella of Salmonella typhi induced an antibody response which was 88% IgG3. S14PS-bovine serum albumin was injected with block copolymer L121 or Quil A in squalane-in-water emulsions. The copolymer L121 was at least as effective as Quil A or complete Freund adjuvant in inducing IgG antibodies. IgG1 was the dominant subclass for all. Addition of monophosphoryl lipid A, but not the threonyl derivative of muramyl dipeptide or nontoxic Rhodopseudomonas sphaeroides lipopolysaccharide, to copolymer L121 increased production of the IgG2a, IgG2b, and IgG3 subclasses. S14PS-flagella with copolymer L121 induced higher titers with a markedly altered isotype distribution: 13% IgG1, 52% IgG2a, 6% IgG2b, and 29% IgG3. Monophosphoryl lipid A added to L121 reduced IgG1 antibody to 5%, but increased IgG2a antibody to 14%, IgG2b antibody to 3%, and IgG3 antibody to 78%. These studies demonstrate that both the carrier and the adjuvant can influence the titer and isotype distribution of antipolysaccharide antibody responses. PMID- 1855993 TI - Endotoxin tolerance: independent regulation of interleukin-1 and tumor necrosis factor expression. AB - The injection of lethal or sublethal doses of bacterial lipopolysaccharide (LPS) into mice results in transient increases in both serum tumor necrosis factor (TNF) and interleukin-1 (IL-1). The peak in serum TNF was detected prior to maximal elevation in endogenous corticosterone and was no longer apparent 3 to 4 h post-LPS injection, a point at which corticosterone and IL-1 levels had significantly increased. The initial increase in serum IL-1 may, in part, be modulated by the preceding TNF peak, as pretreating animals with a monoclonal antibody against murine TNF resulted in a significant decrease in IL-1 levels 3 h post-LPS injection. A second injection of LPS at 20 h failed to result in a secondary TNF peak, suggesting an endotoxin-tolerant state. However, in contrast to TNF, significant increases in serum IL-1 were detected in the endotoxin tolerant animals following a repeated LPS stimulus. This secondary increase in IL 1 occurred despite the elevation in serum corticosterone. While peritoneal macrophages from endotoxin-tolerant mice demonstrated only a modest 10 to 15% increase in TNF and IL-1 mRNA relative to the levels after the primary 1-h LPS stimulus, a secondary increase in IL-1 but not TNF mRNA in the spleen was apparent following a second LPS injection. The spleen, however, was not essential for the increase in serum IL-1, as endotoxin-tolerant splenectomized mice had comparable increases in IL-1 following a repeated LPS stimulus. These results demonstrate the differential regulation of IL-1 and TNF in vivo during endotoxin tolerance. PMID- 1855992 TI - Humoral immune response to an antigen from Porphyromonas gingivalis 381 in periodontal disease. AB - The humoral immune responses of patients with periodontitis were evaluated to characterize the host response to Porphyromonas gingivalis. A sonic extract of P. gingivalis 381 from whole cells was fractionated by gel chromatography and ion exchange chromatography. The fractionated extracts were evaluated by Western blot (immunoblot) analyses with patient sera. A dominant antigen was identified from the sonic extract with an apparent molecular mass of 53 kDa. The 53-kDa protein antigen (Ag53) was purified by affinity chromatography by using a monoclonal antibody. Ag53 was detected on the vesicle surface of P. gingivalis 381 by immunoelectron microscopy by using the monoclonal antibody and was detected as a major protein in the outer membrane and in vesicles by Western blot analysis. Monoclonal antibody cross-reactivity to Ag53 in the sonic extracts of P. gingivalis ATCC 33277, P. gingivalis 1021, and Porphyromonas endodontalis ATCC 35406 was revealed. Seventy-seven patients with periodontitis were examined for their responses to Ag53. Serum immunoglobulin G (IgG) from 54 patients reacted strongly to Ag53; however, serum IgG from the remaining 23 patients did not exhibit detectable reactivity at all to Ag53, even though the patients had high serum IgG titers to the sonic extract. Ag53 is a new marker that represents an interesting aspect of the humoral immune response to P. gingivalis in patients with periodontitis. PMID- 1855995 TI - Characterization of Borrelia coriaceae antigens with monoclonal antibodies. AB - Three monoclonal antibodies (F6F3, F6B11, and F6B3) were developed against Borrelia coriaceae antigens. All three antibodies appeared to be specific for this species and did not cross-react with Borrelia burgdorferi (strains B31 and IRS), Borrelia hermsii, Borrelia anserina, Leptospira interrogans serovar hardjo, or Treponema hyodysenteriae, as determined by indirect fluorescent antibody staining, enzyme-linked immunosorbent assay, and Western immunoblot analysis. Only one of these antibodies, F6B3, bound to spirochetes present in organ smears from the argasid tick, Ornithodoros coriaceus. The antigens recognized by F6F3, F6B11, and F6B3 have apparent molecular weights of ca. 37,000, 35,000, and 16,000, respectively, as determined by Western blot analysis. Antigens were analyzed by immune electron microscopy as well as Western blot and indirect fluorescent antibody staining analysis of spirochetes after enzyme (trypsin and protease K) and detergent (Triton X-100) treatments. These studies suggest that all three antigens are integral membrane proteins. The characteristics of the 37K and 35K proteins are consistent with the outer surface proteins of B. burgdorferi (OSP A and OSP B) described by Barbour et al. (A. G. Barbour, S. L. Tessier, and S. F. Hayes, Infect. Immun. 45:94-100, 1984), while data regarding the 16K protein are less conclusive but may suggest a cytoplasmic membrane location. We suggest that the 37K, 35K, and 16K antigens be designated integral membrane proteins A, B, and C, respectively, as a result of these studies. PMID- 1855994 TI - Phospholipase activity of Mycobacterium leprae harvested from experimentally infected armadillo tissue. AB - Three types of phospholipase activity--phospholipase A1, A2, and lysophospholipase--were detected in Mycobacterium leprae harvested from armadillo tissue at about 25% of the specific activity found in a slowly growing mycobacterium, Mycobacterium microti, which was grown in medium to optimize its phospholipase activity. The highest activity found was lysophospholipase, which released fatty acid from 2-lyso-phosphatidylcholine. Phospholipase activity was detected by using phosphatidylcholine and phosphatidylethanolamine. Differences in relative activities with these three types of substrate distinguished phospholipase activity in M. leprae extracts from armadillo liver extracts. Furthermore, retention of activity in M. leprae after NaOH treatment showed that the activity associated with M. leprae was not host derived. The specific activity of phospholipase was 20 times higher in extracts of M. leprae than in intact M. leprae organisms. Diazotization, a treatment which abolishes activities of surface enzymes exposed to the environment by the formation of covalent azide bonds with exposed amino groups, did not affect M. leprae's phospholipase activity, with one exception: release of arachidonic acid from phosphatidylcholine, which was partially inhibited. Phenolic glycolipid I, the major excreted amphipathic lipid of M. leprae, inhibited phospholipase activity, including release of arachidonic acid, for both M. leprae- and armadillo-derived activity. PMID- 1855996 TI - Virulence of Wolinella recta in a murine abscess model. AB - The virulence of Wolinella recta isolates was studied in an experimental animal model by using monoinfection of BALB/c mice. Infection with clinical isolates of W. recta 576 and W. recta 234 induced dry, flat, depressed gangrenous necrotic skin lesions, whereas W. recta ATCC 33238 failed to induce a similar lesion. Histological examination of the skin lesion 72 h postinfection revealed coagulation necrosis of the epidermis, subcutis and cutaneous truncus muscle, with marked exudation of serum proteins and neutrophils. Virulence-modulating agents such as dexamethasone, galactosamine, hydrazine sulfate, and dextran microcarrier beads were used in conjunction with W. recta infection. Dexamethasone, hydrazine sulfate, and dextran beads enhanced the infectivity and pathogenicity of W. recta for lesion formation and tissue destruction compared with what was found in untreated control mice. Galactosamine sensitization enhanced the virulence potential of W. recta to such an extent that a lethal outcome was observed. Laboratory passage of clinical isolates demonstrated a decreased virulence in high-passage strains, which correlated with the minimal virulence observed in the extensively passaged W. recta ATCC 33238. Serum immunoglobulin G (IgG) and IgM responses were detected in the serum of infected animals, and cross-reacting antibody indicated variation in the antigenic makeup of various W. recta strains. Enhanced IgG antibody responses were observed following the secondary challenge. Mice with acquired antibody response to initial infection remained susceptible to lesion formation with subsequent challenge, but the size of the lesion was significantly reduced, indicating partial protection. Serum IgG and IgM antibody levels were significantly increased by active immunization when compared with levels in mice which had recovered from infection. The immunization significantly decreased the lesion size; however, even these high levels of antibody failed to abrogate the lesion induction. PMID- 1855997 TI - In vivo depletion of natural killer cell activity leads to enhanced multiplication of Mycobacterium avium complex in mice. AB - Earlier investigations have shown that murine natural killer (NK) cells inhibit the growth of fungal and bacterial pathogens in vivo and in vitro. In order to define the role of NK cells in Mycobacterium avium complex infection, in vivo depletion of NK cells by using anti-NK1.1 monoclonal antibody and conventional anti-asialo-GM1 antibody has been attempted. Repeated injection of 200 micrograms of anti-NK1.1 or 50 micrograms of anti-asialo-GM1 antibody effectively depleted NK activity in the spleens of C57BL/6 mice. The growth kinetics of M. avium complex over a period of 4 weeks showed that the colony counts in the spleens of the antibody-treated group were significantly (P less than 0.01) higher than those of the control group and compared well with those of the genetically NK cell-deficient C57BL/6 bg/bg mutant. The alternate strategy of in vivo stimulation of NK activity by poly(I:C) administration did not show a similar reduction in CFU in the spleen compared with the untreated control. The in vivo antibody depletion of NK activity provides direct evidence on the role of NK cells in the control of intracellular mycobacterial pathogens such as M. avium complex. PMID- 1855998 TI - Antibody response of humans to the circumsporozoite protein of Plasmodium vivax. AB - We studied the interaction of sera from residents of an area in northern Peru where vivax malaria is endemic with four recombinant DNA-derived circumsporozoite (CS) proteins of Plasmodium vivax. The antigens used in the enzyme-linked immunosorbent assay included one Escherichia coli-produced and three Saccharomyces cerevisiae-produced recombinant proteins. Three of the proteins (NS1(81)V20, Vivax-1, and Vivax-2) contain the entire central repeat region of the P. vivax CS protein, and one protein (Vivax-3) contains only two repeat sequences. Vivax-1, Vivax-2, and Vivax-3 contain different lengths of sequences flanking the repeats. A higher percentage of the sera had antibodies to Vivax-2 and Vivax-3, the two proteins containing the longest nonrepeat sequences, than to NS1(81)V20 or Vivax-1. Children less than 5 years of age did not have immunoglobulin G antibodies to NS1(81)V20; however, they had antibodies to Vivax 1, Vivax-2, and Vivax-3. The finding that individuals living in a malaria-endemic area produce antibodies to peptides containing nonrepeat regions of the CS protein emphasizes the need to characterize the immune response to these regions in naturally exposed and experimentally immunized humans. PMID- 1855999 TI - Stimulation of proteinase and amidase activities in Porphyromonas (Bacteroides) gingivalis by amino acids and dipeptides. AB - Proteolytic enzymes from the organism Porphyromonas gingivalis are believed to be involved in the development of periodontitis. Studies on both crude extracts and purified trypsinlike enzymes from this organism indicate that substantial stimulation of both amidase and proteinase activities can be obtained during incubation with glycine-containing compounds. We postulate that P. gingivalis may have developed this unusual property to take advantage of the glycine-rich environment which occurs during the periodontitis-associated degradation of gingival collagen. The finding of such a stimulation in crevicular fluids from discrete periodontal sites has been correlated with the presence of P. gingivalis and could be utilized for the early detection of infection by this organism during the onset of periodontitis. PMID- 1856000 TI - Toxoplasmacidal activity of macrophages activated by recombinant major surface antigen (P30) of Toxoplasma gondii. AB - Recombinant major surface antigen (P30), which was produced as a glutathione S transferase (EC 2.5.1.18) fusion protein of Toxoplasma gondii, was found to be able to activate macrophages to kill T. gondii in vitro. The macrophage activation was due to P30 in the fusion protein, not to glutathione S transferase. PMID- 1856001 TI - Cloning and sequence analysis of the major outer membrane protein gene of Chlamydia psittaci 6BC. AB - The gene encoding the major outer membrane protein (MOMP) of the psittacine Chlamydia psittaci strain 6BC was cloned and sequenced. N-terminal protein sequencing of the mature MOMP indicated that it is posttranslationally processed at a site identical to the site previously identified in the MOMP of Chlamydia trachomatis L2. The nucleotide sequence of the C. psittaci 6BC MOMP gene was found to be 67 to 68% identical to those of human C. trachomatis strains, 73% identical to that of Chlamydia pneumoniae IOL-207, 79% identical to that of the C. psittaci guinea pig inclusion conjunctivitis strain, GPIC, and 83% identical to that of the C. psittaci ovine abortion strain S26/3. In contrast, the 6BC sequence was found to be greater than 99% identical to the sequences reported for two strains of C. psittaci, A22/M and Cal-10 meningopneumonitis, believed to be of nonpsittacine avian origin. Monoclonal antibody analysis confirmed the nonpsittacine avian origin of A22/M but identified the Cal-10 strain from which the MOMP gene was previously sequenced as a psittacine strain. These results confirm that psittacine and nonpsittacine avian strains of C. psittaci are closely related and distinct from the mammalian guinea pig inclusion conjunctivitis and ovine abortion strains of C. psittaci. PMID- 1856002 TI - Streptococcus pneumoniae produces at least two distinct enzymes with neuraminidase activity: cloning and expression of a second neuraminidase gene in Escherichia coli. AB - A gene from Streptococcus pneumoniae was cloned in lambda EMBL301 and then expressed in Escherichia coli, which cleaved the fluorogenic neuraminidase substrate 2'-(4-methylumbelliferyl)-alpha-d-N-acetylneuraminic acid. The cloned gene therefore encodes an enzyme with neuraminidase activity. On the basis of restriction mapping and DNA hybridization studies, this gene could be distinguished from another pneumococcal neuraminidase gene cloned previously (A. M. Berry, J. C. Paton, E. M. Glare, D. Hansman, and D. E. A. Catcheside, Gene 71:299-305, 1988). Both neuraminidase genes were found in each of five isolates, covering at least three serotypes, of pneumococci tested. PMID- 1856003 TI - [Lipolysis and lipid oxidation of weight stable patients with malignant tumors of the digestive system]. AB - Tumor-caused weight loss is frequently associated with a high rate of lipolysis and fat oxidation. In order to differentiate the effect of weight-loss from the tumour-dependent regulation of fat metabolism, we studied weight-stable and well nourished patients (ideal body weight 109 +/- 4% (+/- SEM), body mass index 25.1 +/- 0.9 kg/m2). Parameters of lipolysis (glycerol-, fatty acid concentrations) and the calorimetric determined fat oxidation rate of five male tumor patients were examined before and during an euglycaemic insulinclamp (0.2 mU insulin/kg/min). Concomitant with a high rate of lipolysis (glycerol concentration 112 +/- 20 mumol/l, free fatty acid concentration 0.72 +/- 0.13 mmol/l) and fat oxidation (60% of energy expenditure) there was a low normal insulin level (5.9 +/- 0.5 mU/l). Insulin reduced lipolysis and fat oxidation and stimulated glucose oxidation. Weight-stable tumor patients have a high basal rate of lipolysis and fat oxidation; yet the insulin dependent regulation of the fat metabolism is intact, as we have already shown for weight-losing cancer patients. PMID- 1856004 TI - [Short-term infusion therapy in childhood. A comparison of individually mixed with commercial infusion solutions]. AB - Data of parenteral sodium dosage in healthy children recommended by several textbooks vary by the factor 4. Therefore, we studied the effect of low and high i.v. dosage administered in 5-5.5% glucose for 12 hrs to probands without renal disease. Group 1: n = 13; Na 2.2 +/- 0.4, K 1.7 +/- 0.2, Cl 4.2 +/- 0.6 mmol/kg/d, individually composed solutions. Group 2: n = 17; Na 5.1 +/- 1.3, K 1.6 +/- 0.5, Cl 5.8 +/- 1.5, acetate 2.4 +/- 0.6 mmol/kg/d; Ca, Mg, malate, glycerol phosphate below 0.3 mmol/kg/d; commercial ready-for-use mixtures. Compared to the control period, the excretion of Na into the urine was unchanged in group 1 during the infusion but significantly lowered in group 2. Regression analysis reveals that infusion of 2.7 mmol Na/kg/d would have given a balanced sodium balance. The real parenteral requirement, however, may be below this value, as the excretion of Na during the control period indicates that the probands in both groups were overloaded with Na before the beginning of the study. During infusion, the renal clearance of creatinine was unchanged in group 1 but significantly lowered in group 2 (131 +/- 58 vs. 94 +/- 38 ml/min/1.73 m2; p less than 0.01). We would like to recommend to elucidate the mechanism and the clinical significance of this effect before using the commercial solution in clinical routine. PMID- 1856005 TI - Fluctuation of anti-A and anti-B histo-blood-group antibodies in a patient after liver transplantation. AB - The concentrations of anti-A and anti-B IgM and IgG antibodies have been studied in the serum of a patient with blood group AB who received a type A donor liver. A newly developed ABO-ELISA was used for this purpose and the values were compared to hemagglutination titers. During the postoperative study period over 8 weeks, the anti-A and anti-B levels showed a higher fluctuation than was measured in preoperative samples. Thus, in this AB-type patient, anti-A IgM varied 10 fold, anti-A IgG 20-fold and anti-B IgG 16-fold. Peak values corresponded to rejection episodes. Immunoactivation in the patient was further documented by the presence of abnormally high levels of soluble interleukin-2 receptors (sIL-2R) in serum samples. The study shows that monitoring of anti-A/B antibodies may represent a further criterion to follow-up transplanted patients during the critical postoperative graft acceptance period. PMID- 1856006 TI - [Decrease in the concentration of tobramycin, vancomycin and phenobarbital in administration with infusion filter]. AB - To assess the loss of drugs to in-line filters, concentrations of tobramycin, vancomycin, and phenobarbitone were determined in vitro in samples recovered upstream and downstream of the filter. Binding of the drugs to new filters was higher than to used filters. With bolus administration, the concentrations of vancomycin and phenobarbitone were reduced by 1% when using old filters and by 4% when using new filters. Tobramycin concentrations were reduced by 7 and 12%, respectively. With continuous administration of the drugs, binding was highest during the first half hour. Differences between new and used filters were also seen with continuous administration: The cumulative loss was 5% higher with new than with old filters. This difference in binding between filters may stem from a saturation of free binding sites. Tobramycin showed the highest binding to the in line filter. The extent of adsorption of tobramycin to intravenous filters may be considered moderately important in adult patients. The adsorption of vancomycin and phenobarbitone is not clinically relevant in adult patients. PMID- 1856007 TI - Internal and external quality control in the toxicological analysis of blood and urine samples in the Federal Republic of Germany. AB - Due to a technical rule for dangerous agents (TRGS 410), issued by the Ministry of Labor in the Federal Republic of Germany in 1979, toxicological analyses in biological materials must be carried out under conditions of "statistical quality control". This quality-control scheme provides internal and external control programmes. For internal quality control, the results of many years of experience with five commercially available control specimens and one "home-made" control have been evaluated. The control samples showed good, comparable results over a long period. Except in a few cases, there was good agreement between our results and the assigned values. Since 1982, the German Society of Occupational Medicine has offered eight intercomparison programmes for external quality. In samples from 80-90 laboratories, 6 metals in blood and around 20 inorganic and organic parameters in urine in 2 concentration adjustments have been analysed. Successful participation was certified if both results obtained for one parameter were within the tolerance range (assigned value +/- 3 SD). The average success rate was around 60%. PMID- 1856008 TI - Work with chemicals on deck of Norwegian chemical tankers. AB - The chemical environment on deck of Norwegian chemical tankers in 1985/1986 is described using information obtained from an interview of 85 seamen. The seamen are exposed to vapours from volatile chemicals during several working operations, such as loading, unloading and cleaning of the tanks. The major exposure is probably to organic solvents and other hydrocarbon compounds, both in the cargo and in the chemicals used in the cleaning processes. Captains experience almost no chemical exposure. Mates, pumpmen and able seaman may receive exposure of a similar kind and magnitude, but there are individual differences within each group of seamen. The eldest seamen seem to be more exposed to chemicals than the younger. Symptoms of acute intoxication occur in 35% of the seamen, related to work with organic solvents, to tank cleaning work and to insufficient use of protective respiratory equipment. Improvements of the chemical environment on board are recommended, to prevent acute and chronic effects of volatile chemical compounds. Better information concerning chemical hazards and prevention of these on chemical tankers seem to be of major importance. PMID- 1856009 TI - Effect of lead on cardiac parasympathetic function. AB - A cross-sectional survey was performed on 172 male, lead exposed workers to clarify the effects of lead on the cardiac autonomic nervous system expressed as the decrease of R-R interval variation on an electrocardiogram and to obviate the dose-effect relationship between blood-lead level (Pb-B) and the degree of the decrease. For 132 workers who were exposed to lead for more than one year and whose Pb-B levels were relatively stable (Pb-B variation less than 20 micrograms/dl during recent one year), a significant dose-related decrease of R-R interval variation during deep breathing was observed. Age-adjusted R-R interval variation during deep breathing in those whose Pb-B were 30 micrograms/dl or above was significantly decreased compared with those whose Pb-B levels were 20 micrograms/dl or below. This decrease was observed more clearly in younger workers. These results suggest that an effect on autonomic nervous system expressed as decrease of R-R interval variation during deep breathing might be one of the earliest effects of lead exposure. PMID- 1856010 TI - A study of the prevalence of acute respiratory disorders among workers in the textile industry. AB - An epidemiological study of 774 workers in seven eastern France cotton textile factories was conducted to determine the prevalence of acute respiratory disorders. From nine non-textile companies, 464 workers, stratified as to sex, age and tobacco consumption participated in the study as a control population. A questionnaire designed to elicit the respiratory symptoms (in particular the Monday tightness characterizing byssinosis) was administered to the 1238 workers. Peak-expiratory-flow (PEF) measurement was made for each subject, exposed and non exposed, before the start of the shift on the day of the worker's return to work and repeated at the end of the shift. The PEF's variations during the workshift were studied. Present Monday tightness was mentioned by 48 cotton exposed workers (6.2%) and by 9 non-exposed (1.9%) (P less than 0.001). A 10% decrease in PEF during the shift was present in 63 cotton exposed workers (8.1%) and in 10 non exposed (2.1%) (P less than 0.001). For the exposed population, Monday tightness was analysed using multiple logistic regression, showing an absence of a link with smoking, an increased occurrence after 20 years of exposure (OR = 7.3) and a link with current job (more frequent among those with the dustiest jobs) (OR = 4.9). The multiple logistic analysis of a 10% decrease in PEF showed effects of smoking habits (OR = 1.86). It also showed a link with "highly polluted job" history (OR = 2.7), but especially with present job (OR = 3.4). The absence of a constant link between Monday tightness and drop of the PEF was found. PMID- 1856011 TI - Urinary 2,5-hexanedione assay involving its conversion to 2,5-dimethylpyrrole. AB - High-performance liquid chromatography (HPLC), gas chromatography (GC) and spectrophotometry were used to examine 2,5-dimethylpyrrole, derived from 2,5 hexanedione in the acid-hydrolyzed urine of subjects exposed to n-hexane. The urine of a subject exposed to n-hexane was hydrolyzed with hydrochloric acid and then neutralized. Thereafter, 2,5-hexanedione in the hydrolysate was heated with ammonium carbonate to yield 2,5-dimethylpyrrole. A methanol extract of the 2,5 dimethylpyrrole formed was subjected to HPLC and an ethylacetate extract of it was subjected to GC, with a flame thermoionic detector (FTD). For spectrophotometry, the ethylacetate extract was allowed to react with Ehrlich's reagent and then the absorbance of the colored compound formed was read at 525 nm. Pyrrole condensation with ammonia is specific to 1,4-diketones and these three assay methods can be used for determination of 2,5-hexanedione in the urine of workers exposed to n-hexane. The hydrolytic conditions for urine of subjects exposed to n-hexane for analysis of 2,5-hexanedione were discussed. PMID- 1856012 TI - Quality control program on biological monitoring by Japan Federation of Occupational Health Organizations. AB - Since 1980, the Japan Federation of Occupational Health Organizations has been conducting an external quality control survey for biological monitoring under a contract with the Ministry of Labour of the Japanese Government. The number of participating organizations has increased from 91 in 1980 to 179 in 1987. The items in the program were lead and free erythrocyte protoporphyrin concentrations in blood, and lead, coproporphyrin, delta-aminolevulinic acid, chromium, hippuric acid, methylhippuric acid, total trichloro-compounds, mandelic acid, and phenol concentrations in urine. Evaluation was based on a scoring system. The scores were on the slope of major axis for probable ellipse, the slope of regression line, square root of error mean square for regression, performance indices, and the difference between 'true' and observed values of each sample. There was a gradual improvement in the evaluation scores as a function of time. The improvement was paralleled by the adoption of modern analytical methods such as flameless atomic absorption spectrometry for blood-lead measurement and high performance liquid chromatography for urinary hippuric acid determination in many participants. These methods are simple in operation and reliable in performance. It was considered very probable that the program promoted the adoption. PMID- 1856013 TI - Metal concentrations in human lung tissue, with special reference to age, sex, cause of death, emphysema and contamination of lung tissue. AB - Nine element concentrations in the lung tissues of 2,274 autopsies were determined in Japan by atomic absorption spectrometry. The metals determined were iron, calcium, magnesium, zinc, copper, cobalt, nickel, lead, and chromium. The range, mean, standard deviation, mode and median are described for each metal. Moreover, these data were analyzed statistically, based on their sex, age, degree of lung contamination (color and the amount of particle deposition), severity of pulmonary emphysema and cause of death. Iron, calcium, magnesium, zinc, copper and cobalt concentrations in the lung tissue seemed to be affected mostly by physiological variation and the levels in the blood. On the other hand, nickel, lead and chromium concentrations might reflect environmental exposure. Chromium concentration especially increased with age and showed a significantly positive correlation with the degree of contamination and severity of emphysema. PMID- 1856014 TI - Changes of nerve excitability and urinary deltamethrin in sprayers. AB - The nerve excitability of median nerve as well as the urinary deltamethrin and its metabolite dibromovinyl-dimethyl-cyclopropane carboxylic acid (Br2A) were detected in 24 deltamethrin sprayers in an assessment of the exposure and effect of deltamethrin. Twenty-nine male, unexposed referents of the same age range were also selected. The urinary deltamethrin and its metabolite Br2A were detectable by GC and HPLC in the sprayers after exposure. The nerve excitability detected with an electromyograph and pairs of stimuli at variable intervals showed that there was a prolongation of supernormal period in median nerve of the exposed group after a 3-d spraying compared with that before spraying which became more significant 2 d after cessation of exposure. In the mean time, no change of supernormal period in the median nerve of reference group was found at the 3-d interval. Nearly half of the sprayers had a supernormal period prolonged by more than 4 ms after spraying, whereas nearly none of the reference group showed similar changes after repeated examinations. Although there was neither correlation between the nerve excitability changes and the urinary deltamethrin or Br2A excretion, nor was a case of acute deltamethrin poisoning diagnosed, the non invasive technique used for nerve excitability detection in this study seems to be valuable in studying deltamethrin toxicity on human. PMID- 1856015 TI - Effects of diurnal and seasonal sleep deficiency on work effort and fatigue of shift workers. AB - This study was designed to assess and compare the quantity and quality of sleep of morning, afternoon, and night shift workers during the winter and summer seasons, and to evaluate the effects of sleep deficiency on the work effort and fatigue of the workers. The subjects studied consisted of a sample of 150 textile workers, working on a monthly rotating 3-shift system: morning shift (06.00-11.00 and 14.00-17.00) afternoon shift (11.00-14.00 and 17.00-22.00), and night shift (22.00-06.00). Information concerning quantity and quality of sleep were registered daily over a week for every subject. The Ratings of Perceived Effort scale and the Feeling and Symptoms of Fatigue scale were used to collect information about feeling of effort and fatigue of the subjects. The results showed that the duration of sleep length is longest in the afternoon and shortest in the night shift both during summer and winter. The amount of sleep is shorter during summer during all three shifts. The workers spent more effort and felt more fatigued during summer than winter. The shift workers, particularly of the tropical region, like Bangladesh, seem to be worst affected in terms of quantity and quality of sleep, health and well-being due to extremely high temperature (30 45 degrees Celsius) during summer than winter (5-25 degrees Celsius). The workers think that the problems of shift work could be minimized by improving the quality of working and living conditions, reducing cycle of rotation, shortening working day and closing night shift during peak summer. PMID- 1856016 TI - Relationship of airborne endotoxin and bacteria levels in pig farms with the lung function and respiratory symptoms of farmers. AB - Previous studies have demonstrated a high prevalence of respiratory and other symptoms and a decrement in lung function among pig farm workers, although the relationships with specific agents present in the work environment remain obscure. This study was therefore undertaken to investigate the relationship between symptoms, lung function and airborne endotoxin, ammonia and dust levels in piggeries. Information on symptoms, lung function, endotoxin, ammonia and dust levels was available for 183 pig farmers who worked in 136 farms. For 62 farms information was present on the levels of bacteria and gram-negative bacteria. For these 62 farms, endotoxin exposure measurements were taken in more than one stable. In general, no significant correlations were found between lung function and chronic respiratory symptoms, or dust and ammonia levels. The endotoxin concentration in stables was negatively related to most lung function variables, but only for the subgroup of 62 farmers was a statistically significant relationship found between endoxtoxin exposure and FEV1. A borderline statistically significant and negative relationship was found between the endotoxin concentration and the FVC. Symptoms experienced during or shortly after work showed odds ratios larger than one with the levels of bacteria, gram negative bacteria and endotoxin, indicating a positive relationship. No consistency in the relationship between symptoms and dust levels was found. The results suggest that endotoxins and (gram-negative) bacteria probably play an important role in the development of symptoms and lung function changes among pig farmers. PMID- 1856017 TI - Capillary gas chromatographic method for mandelic and phenylglyoxylic acids in urine. AB - In support of an occupational investigation of styrene exposure, a capillary gas chromatographic method was developed for the quantitation of the styrene metabolites mandelic and phenylglyoxylic acids. The method was based on that of Guillemin and Bauer, in which phenylglyoxylic acid was converted to mandelic acid by reduction before instrumental analysis. The earlier method had to be modified for use with capillary columns; the resulting method was sensitive, selective and reproducible. The detection limit was approximately 0.001 mg/ml urine. Approximately less than 5% relative precision was achieved in the range of 0.05-2 mg/ml urine. Mandelic acid was resolved from other components of urine and from by-products of derivatization. PMID- 1856018 TI - Oncogene proteins as biomarkers in the molecular epidemiology of occupational carcinogenesis. The example of the ras oncogene-encoded p21 protein. AB - The use of oncogene proteins as biomarkers offers a new approach to the molecular epidemiologic evaluation of occupational carcinogenesis. The ras oncogene-encoded p21 protein represents a prototype for this type of study, since it is known to be activated by common occupational carcinogens, is frequently found in human tumors of occupational concern, and, at least in certain instances, appears to be expressed relatively early in the disease process, allowing the possibility of early detection and intervention. Herein, we review our experience with the use of immunologic detection of p21 in cohorts with cancer or at risk for the development of cancer due to their occupational exposures. The results suggest that p21 (particularly when used with other oncoproteins and biomarkers such as PAH-DNA adducts) will indeed be a useful addition to the growing armamentarium of molecular epidemiologic biomarkers in the study of occupational carcinogenic mechanisms and in the detection and prevention of occupational cancers. PMID- 1856020 TI - Monitoring exposure to simple epoxides and alkenes through gas chromatographic determination of hemoglobin adducts. AB - A method for monitoring exposure to ethylene oxide (EO) and propylene oxide (PO) and their corresponding alkenes through the analysis of adducts to N-terminal valine in hemoglobin (Hb) using gas chromatography (GC) and electron-capture detection has been developed. The method is a further development of the so called N-alkyl Edman method, which has thus far been carried out using gas chromatography-mass spectrometry (GC/MS). The correlation between GC and GC/MS determinations of adduct levels in human samples was found to be good. The newly developed GC method enables the determination of adducts to Hb from EO and PO down to levels of about 100 pmol/g globin. This adduct level corresponds to the expected increment from ethene in inhaled tobacco smoke in a smoker of about 10 cigarettes/day or from an average exposure to about 50 ppb EO or 1 ppm PO during working hours. PMID- 1856019 TI - Immunological and respiratory changes in soy bean workers. AB - Immunological and respiratory findings were studied in a group of 19 male soybean workers. Twenty control workers also participated in the immunological studies. All soybean workers had positive immediate skin reactions to soybean extract, as did 19/20 control workers. Similarly, 18/19 soy workers reacted to soy antigen prepared after separation from oil, but only 3/19 to soy lecithin antigen and 1 to soy oil antigen. A majority of soy workers (13/19) reacted to house dust. Only 3/19 soy workers had increased levels of soy-specific IgE. The prevalence of chronic respiratory symptoms was higher in exposed than in control workers, being significantly different for dyspnea (P less than 0.01). Workers with increased specific serum IgE or positive skin tests to house dust did not have any more symptoms than workers with negative tests. Ventilatory function was significantly worse in soybean workers than expected. Nevertheless, workers with positive skin or serological tests to house dust had across-shift changes similar to those with negative tests. These data suggest that skin and airway responses to soybean components (particularly the non-lipid ones) are very frequent among soybean workers. In the current study specific (soy) and non-specific (house dust) skin tests and immunoglobulins did not allow us to identify the workers at risk of developing symptoms or lung function abnormalities. This suggests that in addition to any atopic mechanisms, the irritant effect of soy dust may play a role in this occupational airway disease. PMID- 1856021 TI - A new derivatization procedure for the analysis of hippuric acid and m-methyl hippuric acid by gas chromatography. AB - The industrial solvents, toluene and xylene, have physicochemical properties that can be hazardous to the workers exposed. Since hippuric acid and m-methyl hippuric acid represent the products of toluene and xylene biotransformation in urine, they are used as biological markers in studies on occupational exposure to these solvents. Several methods have been used to determine hippuric acid and m methyl-hippuric acid--either based on gas chromatography or on high-performance liquid chromatography. In this study we propose the derivatization of hippuric acid and methyl-hippuric acid using methanol in acid medium (HCl), a low-cost reagent with a low level of toxicity. The method has been routinely used in our laboratory for 1 year and has proven to be a reliable procedure for the biological control of occupational exposure to toluene and/or xylene. PMID- 1856022 TI - An evaluation of heat stress indices (ISO 7243, ISO/DIS 7933) in the prediction of heat strain in unacclimated men. AB - The ISO 7243 heat stress standard based on the wet bulb globe temperature (WBGT) heat stress index and the analytical standard proposal ISO/DIS 7933 were evaluated in eight physically trained and eight untrained, unacclimated men during prolonged light exercise carried out while wearing industrial work clothing. The exercise tests were done in a thermoneutral (20 degrees C/40%), a warm humid (30 degrees C/80% humidity), and a hot dry (40 degrees C/20% humidity) environment. Both of the standards were effective in predicting the excessive thermal strain observed in the dry and humid heat (WBGT, 28 degrees C). In dry heat, neither of the standards took into account the higher sweating capacities of the physically trained men. The large inter-individual variability in the physiological responses to heat stress questioned the calculations of definite allowable exposure times (ISO/DIS 7933). PMID- 1856023 TI - Alterations in lung function due to mixtures of organic solvents used in floor laying. AB - To determine the short-term and long-term effects of organic solvents on the respiratory tract, 26 male floorlayers exposed to organic solvents were compared with 36 persons unexposed to such substances. The investigation primarily included a detailed history, determination of solvent concentration in the air inhaled by the workers, long-term ECG during the entire shift and lung-function test (vital capacity, forced expiratory volume in one second, flow volume curve) as well as non-specific bronchial inhalation challenge using a 3% acetylcholine aerosol before and after the shift. The floorlayers were primarily subjected to inhalative exposure to adhesives containing mixtures of toluene, petroleum hydrocarbons, ethyl acetate, methanol and acetone or one of these substances alone. This frequently resulted in short-term value limit excesses, especially in the MAK value (standardised threshold concentration in Germany) for toluene, which is a prime component of neoprene glue. Of the 26 floorlayers, 6 complained of breathlessness and coughing, whereas 13 suffered from nasal discharge and blockage--symptoms closely related to work. The smokers in this group showed a decline in lung function during the shift--especially in the forced expiratory volume in 1 s (FEV1)--as compared with the non-smokers in this group and the persons in the control group. This probably due to the combination of noxious substances. A strong correlation between occupational age and changes in lung function was observed: the occupationally youngest workers demonstrated the highest decrease in values during the course of the shift. There was no evidence of either obstructive or restrictive respiratory disorders or of marked deviation from the European Community for Coal and Steel (ECCS) references.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856024 TI - Mandatory exercise and heart disease risk in fire fighters. A longitudinal study. AB - After undergoing initial assessments of percentage of body fat (% fat), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and maximal oxygen consumption (VO2Max), a group of 24 paid male fire fighters (mean age, 30.1 +/- 7.7 years) began a mandatory exercise program. The physiological variables mentioned above were assessed once a year for the subsequent 5 years. A repeated measures multivariate analysis of variance followed by univariate post hoc techniques showed a minimal but statistically significant improvement in % fat ( 1.43% +/- 0.66%) and TG (-27.54 +/- 10.44 mg/dl) over the 5-year period. Significant differences in TC, HDL-C, LDL-C, and VO2Max were noted over the years, but their magnitudes were small and no pattern was demonstrated. Each of the 5-year means for TC, LDL-C, % fat, and VO2Max were outside the desirable ranges. We concluded that mandatory exercise programs do not significantly alter the risk factor status or the aerobic fitness levels of fire fighters and that a significant number of the latter demonstrate a higher than average risk for cardiovascular disease. PMID- 1856025 TI - Urinary excretion of chlorinated phenols in saw-mill workers. AB - The excretion and conjugation of chlorophenols were studied in workers exposed to 2,4,6-tri-, 2,3,4,6-tetra-, and pentachlorophenolates, the main components of the chlorophenolate product manufactured by direct chlorination of phenol. The workers were exposed in two different saw mills in which sodium chlorophenolate was used for treatment of lumber during the warm season. Urine specimens were collected at the end of the treatment season as well as at the start of a new treatment period in the spring. Serum specimens were collected towards the end of the treatment period. Total and unconjugated chlorophenols were analyzed with a gas chromatographic method. The maximal concentrations of urinary 2,4,6-tri-, 2,3,4,6-tetra- and pentachlorophenol at the end of the lumber-treatment period were 1-11.8, 3.4-17.3, and 0.2-0.9 mumol/l, respectively, and the average apparent half-times calculated using a one-compartment model were 18 h, 4.3 days and 16 days, respectively. For 2,3,4,6-tetrachlorophenol, the data of some subjects showed a better fit with a two-compartment model; the corresponding half times were 5.3 and 26 days. During the continuous-exposure period the average serum levels of tetra- and pentachlorophenol were rather similar before and after the working day: 2.79 +/- 1.78 mumol/l for tetrachlorophenol and 0.85 +/- 0.4 mumol/l for pentachlorophenol. Renal clearance values for tetra- and pentachlorophenol were related to urine flow and indicated tubular reabsorption. At low concentrations, sulfate conjugation was dominant. With increasing chlorophenol concentrations the proportion of glucuronide conjugation was increased, especially for pentachlorophenol. PMID- 1856028 TI - Factors influencing high rate of 'born-before-arrival' babies in Nigeria--a case control study in Ogbomosho. AB - The purposes of this study were to examine the records of the birth-before arrival mothers in order to identify factors which might explain why so few booked for hospital care and also to identify the post-delivery problem which lead them to seek professional help. Data from the hospital records and interviews with some of the 377 born-before-arrival mothers seen at the Baptist hospital, Ogbomosho, Oyo State, Nigeria between 1982 and 1985 were analysed using descriptive statistical methods. Findings indicated that 65% of the mothers attending after delivery outside hospital had been delivered by a traditional birth attendant. Of these 73.7% sought hospital attention following retained placenta with bleeding. The first step towards improving perinatal care will be the official integration of the indigenous midwives into the national health services to enhance organized programmes of training for the traditional birth attendants. The implications of these findings suggest that traditional birth attendants and professional carers in Nigeria should improve liaison and cooperation between themselves so as to correct the imbalance in health service provision between the major cities and rural areas. PMID- 1856026 TI - Urinary methylhippuric acid isomer levels after occupational exposure to a xylene mixture. AB - The quantitative relationship between exposure to xylene vapor and urinary excretion of methylhippuric acid (MHA) isomers were studied in the second half of a working week. The participants in the study were 121 male workers engaged in dip-coating of metal parts who were predominantly exposed to three xylene isomers. The intensity of exposure measured by diffusive sampling during an 8-h shift was such that the geometric mean vapor concentration was 3.8 ppm for xylenes (0.8 ppm for o-xylene, 2.1 ppm for m-xylene, and 0.9 ppm for p-xylene), 0.8 ppm for toluene, and 0.9 ppm for ethylbenzene. Urine samples were collected at the end of the shift and analyzed for metabolities by HPLC. The statistical analysis showed that there is a linear relationship between the intensity of exposure to xylenes and the concentration of MHA in urine, that the regression line passes very close to the origin, and that the increment in observed (i.e., noncorrected) MHA concentrations as a function of increasing xylene concentration was 17.8 mg x l-1 ppm-1. Further examination on the basis on individual xylene isomers showed that the slopes of the regression lines for o- and m-isomers were similar (i.e., 17.1 and 16.6 mg l-1 ppm-1, respectively), whereas that for p xylene was larger (21.3 mg l-1 ppm-1). PMID- 1856027 TI - Hexahydrophthalic acid in urine as an index of exposure to hexahydrophthalic anhydride. AB - Post-shift and next-morning urine was sampled from workers exposed to hexahydrophtalic anhydride (HHPA), an epoxy hardener, sensitising at low exposure levels. Exposure levels of HHPA in air (gas chromatography, GC) in the range of 30-270 micrograms/m3 corresponded to urinary concentrations of 0.9-2.8 mumol hexahydrophthalic acid (HHP acid; GC-mass spectrometry)/mmol creatinine. In the morning samples the concentrations were less than 0.04-0.3 mumol HHP acid/mmol creatinine. In unexposed controls, the level was less than 0.1 mumol/mmol creatinine. A correlation was found between the time-weighted levels of HHPA in air and HHP acid in the post-shift urine (rs = 0.93; P less than 0.023), indicating that the determination of HHP acid in urine is suitable for biologic monitoring of HHPA exposure. PMID- 1856029 TI - A comparison of the mealtime care given to patients by nurses using two different meal delivery systems. AB - This study explored the mealtime care given to stroke patients and general patients on the medical wards of two hospitals which operated different meal delivery systems. Overall, nurses in Hospital 1 (in which the patients' food was plated by catering staff in the main hospital kitchen) tended to be less involved in mealtimes than those in Hospital 2 (in which the nurses plated the food on the wards). This was particularly so for the qualified staff and applied to many aspects of mealtime care including meal trolley supervision, the serving and delivery of food, checking patients' well-being, observing their feeding difficulties, providing assistance during mealtimes, and observing the contents of discarded dishes. These differences were not related to staffing levels or the prevalence of feeding problems. It is possible, therefore, that a meal delivery system designed to free nurses from the 'non-nursing' duty of serving food may have an adverse effect on their involvement in other aspects of mealtimes. PMID- 1856030 TI - Nursing outside hospitals: the working experience of community nurses: job characteristics. AB - The Community Nursing Project reports the results of a mailed questionnaire survey of the working and educational experience of 689 nurses employed outside hospitals and nursing homes in Victoria in 1985. This paper reports that part of the study relevant to their practice settings, job titles, job content and working conditions. Confusion about titles for community nurses was evident given that subjects offered 281 separate job titles. A title with the general form 'Community Nurse--specialist designation' was acceptable to 88% of nurses. Eighteen (of 57) job activities were identified that were performed at least weekly by four of the six principal practice areas. Therefore while the concept of the generic community nurse is a meaningful one, it is only so when the differences in job content across practice areas are acknowledged. Medical clinic nurses however do not conform to this general pattern. Seventy-nine per cent of the nurses currently had a job description. However, only 45% had a statement of job conditions, 26% had a formal job orientation, 24% worked overtime unrewarded by payment or time in lieu and only 59% could reschedule their work times. These figures varied greatly between practice areas. It is suggested that the concept of the community nurse--specialist designation be promoted. Specifically this could be done by the adoption of this title and the development of appropriate post-basic educational courses. While these conclusions have most relevance for Australia, they will also be of interest to nurses of other countries where an increasing emphasis on primary health care has resulted in an expansion of community nursing practice. PMID- 1856032 TI - Social correlates of satisfaction and stress among Israeli nurses within intensive coronary care units (I.C.C.U.s). AB - This study focuses on job satisfaction and work-related stress of nurses within the Israeli I.C.C.U.--a complex technological environment. The main purpose was to assess the contribution of multiple factors which may be associated with the nurses' level of satisfaction and stress. These factors include personal characteristics and professional attributes of the nurse, as well as some objective and subjective characteristics of their work setting. In general, with the exception of income, nurses are satisfied. Stress presents a big problem in the I.C.C.U. Structure of work was found to be correlated with satisfaction, but only partially with stress. It was deduced that nurses are willing to 'pay the price' of professionalization: to work under stress and yet be autonomous, take responsibility for work decisions, and be highly involved in work, thus gaining satisfaction. PMID- 1856031 TI - Nurses' interpersonal behaviours and the development of helping skills. AB - This study investigates the interpersonal behaviours of general nurses and evaluates the effectiveness of a nine-week program in developing helping skills. Ninety-nine nurses undertaking tertiary studies were administered the FIRO-B Scale, which assesses six dimensions of interpersonal behaviours, before and after the skills program. Changes in interpersonal behaviours were examined for the total sample and for six clinical subgroups based on the nurse's area of clinical practice. Nurses' FIRO-B scores at pre-test were also compared with results from a sample of occupational therapy students. The results of this study showed that nurses, when compared with occupational therapists, had less desire to belong and a stronger need to influence or control interpersonal relationships. When clinical subgroups of nurses were contrasted, significant differences in the need for inclusion and affection were identified. Evaluation of the communication skills program demonstrated some significant improvements in helping attitudes for the sample as a whole, but no differences when specific nursing subgroups were examined. Findings from this study are discussed in relation to the helping role of nurses, methodological limitations, and directions for future investigation. PMID- 1856033 TI - Educational activities on wards under 12 hour shifts. AB - Interest in 12 hour nursing shifts has renewed in response to demands for improved cost effectiveness in the NHS. But the effects of the shift on nursing education are unclear. A repeated measures study was conducted, using activity analysis to record patterns of nursing and educational behaviour under a 12 hour as compared to an 8 hour shift. Lower levels of ward based education occur under the 12 hour shift. Students pair up with trained staff less. Rather they work alone or with other students more. They also have less contact with patients than under an 8 hour shift. PMID- 1856034 TI - Nurses' assessment of elderly patients in hospital. AB - Nurses' assessment of patients' mobility in hospital provided the focus for an inductive qualitative study which examined how an everyday aspect of nursing practice was carried out. The study described assessment practices in both long term care and acute care wards for elderly patients as a situated activity. Interviews with nurses, as well as observation of their activities and records, resulted in explanations of their behaviour as deriving from their conceptions of ward functions. These conceptions arose from their adoption of the values of cure and discharge and so, in the different types of ward, assessment held different meanings and was carried out in different ways. The findings have implications for nursing practice in different settings but also for the care of elderly and chronically ill patients, where cure is an inappropriate end goal of care. This example of developing explanatory theory inductively also has implications for the development of mid-range nursing theory and suggestions are made for its extension. PMID- 1856035 TI - Staff burnout in dementia care--relations to empathy and attitudes. AB - Sixty nursing staff in geriatric and psychogeriatric care (RNs, LPNs and nurse's aides) were selected to be studied on two occasions with an interval of one year regarding the relationships between their experience of burnout, empathy and attitudes towards demented patients. A semistructured interview was performed on the second occasion to learn more about their work experience and to relate the ratings of burnout, empathy and attitudes to their experience at work. The staff's experience of burnout changed from a mean score of 2.7 in 1987 to 2.5 in 1988. Their empathic ability was moderately high and increased from 398 (m) in (1987) to 450 (m) in 1988. The attitudes of staff remained unchanged from 1987 to 1988 and no differences were found regarding the staff's age, place of work or time at present place of work. As for the staff's empathy, there was no difference with respect to sex, category of staff or place of work. RN's showed the most positive attitudes towards demented patients both in 1987 and 1988 and differed compared to the nurse's aides and LPN's. Burnout correlated with lower empathy and less positive attitudes in the staff. Regression analysis showed that 'experience of feed-back at work' and 'time spent at present place of work' were the most important factors when explaining burnout among the staff. Staff with high empathy experienced "a close contact with the patient" as the most stimulating factor at work while staff with low empathy experienced "improvement of the patient's health" and "contact with colleagues" as the most stimulating factors. The importance of counteracting burnout in the care of demented patients is stressed. PMID- 1856036 TI - The experiment: is it worthwhile? AB - Parallel developments in social and educational research as well as more explicit humanistic philosophies of nursing have influenced views on what types of investigation are acceptable or useful to this field. Shifts in opinion towards more participative and qualitative studies reflect the move away from the predominant traditions of medical research and the experiment. This paper attempts to explore the reasons for such a change and examine the related criticisms of the positivist school and in particular deductive experimental approaches in order to assess whether such approaches should continue to have a role in building nursing knowledge. PMID- 1856037 TI - Nurses caring for the terminally ill in the community: a review of the literature. AB - The review considers the literature covering both general district nursing and specialist nursing provision for the terminally ill in the community over the last 10 years in the United Kingdom. It looks at the theoretical and methodological issues associated with research in this area and offers critiques of a number of individual studies in the light of these issues. Research findings are subject to limited comparative analysis and tentative conclusions are drawn regarding the model of care best suited to the needs of those dying at home. Recommendations for future areas of nursing research are made. PMID- 1856038 TI - Assessment of vitamin A deficiency in Republic of Malawi by impression cytology method. AB - During a countrywide survey, we assessed the prevalence of vitamin A deficiency by impression cytology method with transfer in a randomized sample of 650 representative of the children's population of the Republic of Malawi. A vitamin A deficiency was indicated by the results of the ophthalmic examination (XN = 1,4%; X2 = 0,2%) and the ICT test (22% with deficient cytology). Results of ICT were related to age. Vitamin A deficiency seems to be a public health problem in the Republic of Malawi. PMID- 1856039 TI - Diet-induced calciuria and nephrocalcinosis in female rats. PMID- 1856040 TI - Effect of vitamin A supplementation of plasma progesterone and estradiol levels during pregnancy. AB - The effect of vitamin A supplementation on plasma estrogen and progesterone were studied in pregnant women. While there was no change in the estrogen concentration, the mean increment in plasma progesterone in the supplemented group was significant when compared to the unsupplemented group. It is suggested that vitamin A supplementation to undernourished pregnant women may have beneficial effect on feto-placental function. PMID- 1856041 TI - The tocopherol, tocotrienol, and vitamin E content of the average Finnish diet. AB - The Finns average intake of tocopherols, tocotrienols, and vitamin E (alpha tocopherol equivalents) was determined. The food consumption data were derived mainly from the national food balance sheets (for 1987). The average Finnish daily diet was composed and analyzed both in spring and in autumn in order to minimize the effect of seasonal variation. The four tocopherols and four tocotrienols were then determined using high-performance liquid chromatography (HPLC). For comparison, the intake of vitamin E compounds was also calculated using the most recent Finnish analytical data on tocopherols and tocotrienols in food. According to the analytical results, the average daily vitamin E intake in Finland was 10.7 mg alpha-tocopherol equivalents (alpha-TE) of which amount 85% is due to alpha-tocopherol. The analyzed values (10.8 mg alpha-TE in spring and 10.7 mg alpha-TE in autumn) of vitamin E intake did not markedly differ from the calculated value (10.3 mg alpha-TE), thus indicating that the Finnish food composition data upon tocopherols and tocotrienols is up-to-date and accurate. The best food sources of vitamin E were dietary fat (41% of the total amount), cereals (18%), and dairy products and eggs (13%). The average Finnish diet contained 9.5 g of polyunsaturated fatty acids (PUFA), which leads to the ratio of 0.9 between alpha-tocopherol (mg) and PUFA (g). According to these results, the dietary recommendations for vitamin E are met in Finland. PMID- 1856042 TI - Food groups as the source of retinoids, carotenoids, and vitamin A in Finland. AB - The average retinoid, carotenoid, and vitamin A (RE, retinol equivalents) intake of the Finnish population was determined. The food consumption data were derived mainly from the national food balance sheets (for 1987). In this study, the average Finnish diet was composed twice a year, and the retinoid and carotenoid composition was analysed using high-performance liquid chromatography (HPLC). The intake of retinoids and carotenoids was also calculated using the most recent Finnish analytical data on food composition. The vitamin A content of beef, chicken and pork liver, all of which contribute of the vitamin A intake, at different times of the year was determined. The beta-carotene intake in Finland varied between 1700 and 2100 micrograms/day, depending on the season. It is obvious that liver consumption plays a significant role in the vitamin A intake. Since the concentration of retinoids in liver, and especially in pork liver, is extremely high, the average vitamin A intake of the Finnish population may exceed 3000 RE/day. If liver consumption (3.7 g/day) is excluded, the average daily vitamin A intake in Finland is 970-1200 RE, a value in better agreement with the recommended daily allowances. PMID- 1856043 TI - Effect of gamma irradiation on alpha-tocopherol levels in ruminant blood samples. AB - Quantification of circulating levels of vitamin E in free-ranging species can provide useful guidelines for evaluating nutrient status in captive exotic animals. Under current USDA regulations, ruminant plasma or serum samples must be subjected to 1) live-animal testing and viral screening, or 2) gamma (gamma-) irradiation prior to importation. Because irradiation is known to promote free radical formation and destruction of alpha-tocopherol in various tissues, these studies were conducted to evaluate the effect of irradiation on ruminant blood fractions with and without added antioxidant. alpha-tocopherol levels were measured in paired (irradiated vs. unirradiated) plasma or serum samples collected from zoo ruminants (n = 8 spp.). Irradiation caused highly significant (P less than 0.001) but inconsistent destruction of alpha-tocopherol. Addition of 10% volume of a 1% pyrogallol solution to plasma or serum protected against alpha tocopherol deterioration during gamma-irradiation. In order to ensure valid comparative values for vitamin E studies while complying with USDA regulations, it is recommended that plasma or serum samples collected from ruminants outside the US be treated with antioxidant prior to importation. PMID- 1856044 TI - Plasma vitamin A and E in type 1 (insulin-dependent) and type 2 (non-insulin dependent) adult diabetic patients. AB - Vitamin A and E status was studied in 35 type 1 (insulin-dependent) and 35 type 2 (non-insulin-dependent) diabetic patients and in 30 control subjects. Vitamin A blood concentration was significantly decreased in type 1 and increased in type 2 diabetic patients as compared to control subjects. No correlation was found between vitamin A blood concentration and blood glucose control as evaluated with HbA1c. Blood Vitamin E concentrations were significantly increased in both groups of diabetic patients and were statistically correlated with blood cholesterol, apoprotein B and triglycerides, but not with HbA1c. PMID- 1856045 TI - Vitamin C analysis in whole blood, plasma and cells using reduced glutathione as preservative (stabilizer): losses and redistribution. AB - The losses and redistribution of vitamin C in blood fractions (stabilized with reduced glutathione) during 4 hours of storage at room temperature in the dark was studied among 27 elderly women. Storage did not have a statistically significant (p greater than 0.05) effect on the mean vitamin C levels in cells, plasma and whole blood. The results point to a redistribution of vitamin C among blood fractions. It is concluded that vitamin C concentrations in cells rather than in plasma should be the principal indicator of the vitamin C status when blood (stabilized with reduced glutathione) is stored at room temperature before specimen handling. PMID- 1856046 TI - Iron status in Nigerian mothers and their newborns. AB - An evaluation of iron status was carried out on 364 Nigerian pregnant women from Niamey at delivery and in cord blood from their newborns. Anemia, defined as a low hematocrit value, was observed in 46% of pregnant women. Iron deficiency, recognized by a combination of, at least, 2 abnormal values in the 3 independent indicators measured (serum ferritin level, erythrocyte protoporphyrin concentration and transferrin saturation) was present in 47.8% of pregnant women. Anemia was associated with iron deficiency in 60.1% of cases in anemic mothers. A correlation between maternal and newborn iron indicators was found. This study points out the necessity for developing strategies in Sahelian countries to combat iron deficiency during pregnancy by specific measures in combination with more general interventions. PMID- 1856047 TI - The role of zinc in endotoxin fever. AB - Compared to pair-fed controls, zinc deficient rats developed significantly smaller fevers in response to an injection of E. coli endotoxin. PMID- 1856048 TI - Alterations in ruminal utilization of magnesium and zinc in lambs fed different ratios of concentrate: forage. AB - Twelve wether lambs were used to study the effects of concentrate level on ruminal utilization of Mg and Zn. Treatments consisted of concentrate: forage ratios (C:F) of 10:90, 40:60, and 70:30. Ruminal pH.hours (pH x hours area below 6.7 in 24-hour period) increased (P less than .01; linear) with increasing C:F. Bacterial intestinal Mg flow increased (P less than .01; linear) with increasing C:F and was strongly correlated with pH.hours (r = .75, P = .008). Ruminal Mg absorption was not affected (P greater than .05) by C:F, but correlated well with bacterial intestinal Mg flow (r = .66; P = .026). As with Mg, intestinal flow of bacterial Zn increased (P less than .01; linear) with increasing C:F and was highly correlated with pH.hours (r = .76, P = .006). Ruminal Zn absorption declined (P less than .05; linear) with increasing C:F and correlated well with bacterial Zn flow (r = -.82, P = .002). Data suggest that ruminal pH and (or) bacterial accumulation of Mg and Zn may compromise ruminal absorption of these minerals. PMID- 1856049 TI - Chromatography of selenoproteins in human serum using matrix-bound heparin. AB - Since previous experiments indicated that a major selenoprotein in human serum interacts with heparin, chromatography of serum on matrix-bound heparin was studied. When human serum was applied to heparin-agarose columns, approximately half of the applied selenium was not retained on the columns. Approx. 40% of the selenium could then be eluted either with increasing concentrations of heparin or ammonium acetate. Using a scaled-down version of this procedure, selenoproteins from 0.5 ml serum were separated into the heparin-binding and non-heparin-binding fractions. In an experiment where healthy subjects were given supplements of yeast selenium (200 micrograms/d) for eight weeks, the concentration of selenium in serum was almost doubled and then approached the original concentration 16 weeks after the end of the supplementation. During supplementation, no change in the concentration of heparin-binding selenoproteins was observed, and instead the increase in serum selenium occurred in non-heparin-binding proteins. This suggests that the need for selenium by the heparin-binding proteins was saturated already at the starting serum selenium level (1.0 mumol/l). Since interaction with heparin has been observed also for selenoprotein P isolated from rat plasma, the protein in the heparin-binding fraction, demonstrated in this paper, may be a human analogue to selenoprotein P. PMID- 1856050 TI - The influence of dietary lactose on phosphorus-induced nephrocalcinosis in female rats. AB - The effect of dietary lactose, when compared with glucose, on phosphorus-induced nephrocalcinosis was studied in young, female rats. Nephrocalcinogenic diets containing either 0.4 or 0.6% (w/w) phosphorus were used, and lactose was added up to concentrations of 30%. The diets were fed for 28 days. The 0.4 and 0.6% phosphorus diets, when compared with a diet containing 0.2% phosphorus, caused mild and severe kidney calcification, respectively; kidney calcification was demonstrated chemically by the analysis of kidney calcium, and histologically by staining kidney slides for calcium deposits. Dietary lactose caused calciuria, decreased urinary pH and increased cecum weights. The addition of lactose to the diet partly counteracted nephrocalcinogenesis induced by diets containing 0.4% phosphorus, but it did not influence the severity of nephrocalcinosis seen in rats fed diets containing 0.6% phosphorus. It is suggested that high amounts of lactose in the diet have only weak anti-nephrocalcinogenic activity. PMID- 1856051 TI - Effect of thymosin fraction 5 (F5) on erythrocyte glutathione and lipid peroxide levels in hypercholesterolemic rabbits. AB - The effect of thymosin F5 injection on the erythrocyte glutathione levels were investigated in the rabbits fed 2% cholesterol diet for 4 weeks. Although the cholesterol rich diet caused a significant decrease in erythrocyte glutathione levels, erythrocyte lipid peroxide levels were increased considerably. After a cholesterol-rich diet, the rabbits were injected thymosin F5 (0.5 mg/kg body weight, i.p) every other day for 21 days. Thymosin F5 treatment caused a significant increase in erythrocyte glutathione levels. However erythrocyte lipid peroxide levels decreased significantly. These findings suggest that thymosin F5 is effective on both the glutathione concentration and the propagation of lipid peroxidation in red blood cells. PMID- 1856052 TI - Quantitative determination of linoleic acid in infant formulas. AB - The aim of this paper is to develop a gas chromatographic method for the quantitative determination of linoleic acid in adapted, preterm, follow-up and special infant formulas. For sample preparation, lipids were extracted with a Soxhlet extractor after acid hydrolysis, and methyl esters of fatty acids were prepared in a sealed vial with hydrochloric acid in methyl alcohol and analysed using a packed polar column (SP 2330). Triheptadecanoin was chosen as internal standard. The method yielded reliable and repeatable results for all the examined formulas. PMID- 1856053 TI - Decreased plasma esterase-1 activity in rats fed a high-phosphorus diet. PMID- 1856054 TI - [Expectations of the general practitioner from the new psychosomatic medicine]. PMID- 1856055 TI - [Role of the physician in open Europe]. PMID- 1856056 TI - ["Smoking cessation"--a problem for physician and patient]. PMID- 1856057 TI - [Continuing education in the field of internal medicine]. PMID- 1856058 TI - [Heart failure]. PMID- 1856059 TI - [Emergency measures in acute arterial vascular occlusions]. PMID- 1856060 TI - [Emergency measures in respiratory failure]. PMID- 1856061 TI - [Food poisoning]. PMID- 1856062 TI - [Endocrine coma]. PMID- 1856063 TI - [Endoscopic hemostasis of the upper digestive tract]. PMID- 1856064 TI - [Ventilating the cardiac patient]. PMID- 1856065 TI - [Preoperative cardiovascular risk assessment]. PMID- 1856066 TI - [Hypouricemia--a differential diagnostic problem]. PMID- 1856067 TI - [61-year-old patient with diabetes mellitus, weight loss, nausea and vomiting after resection of a pancreatic tumor]. PMID- 1856068 TI - [Pneumocystis carinii pneumonia: possible applications of pentamidine aerosol in hematology, oncology and transplantation medicine]. PMID- 1856069 TI - Management of submandibular gland sialoliths. PMID- 1856070 TI - Department of Public Welfare v. Kallinger. PMID- 1856071 TI - State of Michigan in the Circuit Court for the County of Oakland. PMID- 1856072 TI - The judicial role in life-sustaining medical treatment decisions. AB - Although there has been speculation regarding the pervasiveness and nature of judicial decisions regarding life-sustaining medical treatment (LSMT), no attempt has been made to empirically assess their prevalence or the issues they address. An exploratory study utilizing a mail survey of a nationwide random sample (N = 905) of state trial court judges was conducted to provide initial information regarding this decision-making process. Twenty-two percent of the responding judges had heard at least one LSMT case, and judicial review did not appear endemic to particular states. The number of judges hearing LSMT cases dropped from 1975 to 1981 but has increased since then. Three major issues predominate: patient competency, appointment of a surrogate decisionmaker, and resolution of the ultimate issue of forgoing LSMT. Relatively few cases either contested a prior directive's validity or involved imposing sanctions for instituting or forgoing LSMT. Although subject to different interpretations, the results suggest the courts are having a significant impact on certain aspects of the LSMT decision-making process. However, the infrequency with which any one judge is called upon to make an LSMT decision causes concern about the judiciary's ability to respond in a timely and appropriate manner. With their potential for a profound effect on the actions of health care providers, greater attention to this decision-making process is warranted. PMID- 1856073 TI - Institutional ethics committees and case consultation: is there a role? PMID- 1856074 TI - Ethics committees in hospitals: alternative structures and responsibilities. PMID- 1856075 TI - Payne v. Marion General Hospital. PMID- 1856076 TI - Deel v. Syracuse Veterans Administration Medical Center. PMID- 1856077 TI - Abstracts of papers presented at the Symposium on Polyamines: Biological and Clinical Aspects. June 1-3, 1990, Trento. PMID- 1856078 TI - Limited proteolysis of protein kinase C subspecies by calpain: stimulation by basic polypeptides. AB - Limited proteolysis of Protein Kinase C (PKC) subspecies by Ca(2+)-dependent neutral protease II (calpain II) was remarkably stimulated by the presence of basic polypeptides, such as H1 histone, protamine, poly-L-arginine, and poly-L lysine. The stimulatory effect of basic polypeptides was observed for proteolysis of the active form of PKC which was associated with diacylglycerol and phospholipid. The inactive form of PKC was far less susceptible to proteolysis, either in the presence or absence of the basic polypeptides. The basic polypeptides did not appear to interact with calpain II, but caused a conformational change in PKC to make the kinase molecule more susceptible to proteolysis. The relative rates of cleavage of the active form of types I (gamma), II (beta), and III (alpha) PKC by calpain II in the absence and presence of basic polypeptides were 100:48:23 and 100:100:50, respectively. Available evidence suggests that, like calpain I, calpain II may also contribute to the down-regulation or depletion of PKC. PMID- 1856079 TI - The Maluhia Project: Home Health Care for the Uninsured. AB - This is a report of preliminary findings of the Maluhia Project: Home Health Care for the Uninsured based on its first 12 months of experience in providing services to clients from September 1989 to August 1990. This Project is now in its third year. This report will initially discuss the rationale for Hawaii's participation in this 5-state national demonstration project. It will cover the basic components of the Hawaii Project and its relative impact followed by a brief description of the clients enrolled. A major component of this program is case management. Given the variety of previous programs that have been referred to as case-management services, a comparison has been provided to note significant differences in approaches and target groups between the Maluhia Project and other existing programs. Finally, this report discusses a number of implementation and public policy issues which have emerged and require further discussion. We hope that as a result of this preliminary report from our first 12 months of operation, it will be possible to inform the medical community of the needs faced by this public health problem that has been previously not addressed. PMID- 1856080 TI - A 42-y medical follow-up of Manhattan Project plutonium workers. AB - Twenty-six white male subjects, who worked with plutonium (239Pu) during World War II at Los Alamos, have been given medical examinations periodically over a period of 42 y to identify potential health effects. Inhalation was the primary mode of Pu exposures. The latest examinations, including urine bioassay and in vivo measurements for radioactivity, were performed in late 1986 and 1987. The average age of the 22 living subjects in 1986 was 66 y. The diseases and physical changes noted in these persons are characteristic of a male population in their 60s. Estimates of individual Pu depositions, including lung burdens, as of 1987 or at time of death range from 52 to 3180 Bq (1.4 to 86 nCi) with a median value of 500 Bq (13.5 nCi). Four persons from the original group had died as of 1987. The causes of death were lung cancer, myocardial infarction, accidental injury, and respiratory failure due to pneumonia/congestive heart failure. Expected deaths based on U.S. death rates of white males, adjusted for age and calendar year, are 9.2 based on U.S. rates (standardized mortality ratio = 0.41). Subsequent to 1987, three additional deaths occurred from atherosclerotic heart disease, lung cancer, and osteogenic sarcoma. The bone sarcoma case is discussed in terms of Pu exposure, the natural incidence of this disease, anatomical location of the tumor, and bone tumors observed in Pu-exposed dogs. Plutonium deposition in this man is estimated to have been below current radiation protection guidelines. PMID- 1856081 TI - Metabolism of injected barium in six healthy men. AB - Data are presented on the early metabolism and long-term retention of 133Ba (half life 10.74 y) injected into six healthy male volunteers at ages 25-81 y. The tracer appeared to be mainly skeletal within several days, much earlier than predicted by the ICRP's model of alkaline earth metabolism. Excretion was mainly fecal, the relative fecal:urinary clearance up to 14 d ranging from 6 to 15 in the six subjects. The whole-body retention at 50 d (mean 8%, range 4.5 to 12%) was similar to that inferred from published data on the retention of injected Ra in man (mean 7%, range 3-13%). For about 1 y thereafter, the retention of Ba could be represented by simple power functions of time, with the rate of loss correlating with the excretory plasma clearance rate inferred over the first 4 d. In the subject aged 81 y, the pattern differed from that established following an earlier injection at age 60, but the differences were not necessarily related to advancing age. PMID- 1856082 TI - Radium-226 dose to a boy from playing on mill tailings. AB - Two boys born in September 1949 played on uranium mill tailings from about ages 8 to 12. One of these boys was diagnosed as having leukemia at age 15.5. The 226Ra body burden of the survivor was measured at age 38. The whole-body 226Ra content measured by counting in vivo was 0 +/- 17 Bq and independently by Rn breath analysis as 4.3 +/- 2.1 Bq. At the same time, a control subject with no known exposure to 226Ra, matched in age, height, and weight, was also measured. The whole-body content was estimated as 4 +/- 15 Bq and independently by Rn breath analysis as 5.5 +/- 3.7 Bq. The body burden of the control subject was not significantly different from that of the exposed person. The radiation dose to the marrow-free skeleton assuming a constant 226Ra:Ca ratio since birth was 0.49 and 1.33 mGy at ages 14 and 38, respectively. The radiation dose to the marrow free skeleton assuming 226Ra intake only between ages 8 to 12 was 1.4 and 2.8 mGy at ages 14 and 38, respectively. The best estimate is the mean of these two estimates: 0.9 and 2.1 mGy at ages 14 and 38, respectively. The alpha-particle dose to the red marrow from 226Ra and its decay products was 0.05 mGy at age 14 and 0.10 mGy at age 38. Since no excess was found for the radium dial painters whose doses were much higher, the induction of leukemia by doses of this magnitude would seem quite unlikely. PMID- 1856083 TI - Correlations for predicting air permeabilities and 222Rn diffusion coefficients of soils. AB - The rate of 222Rn gas transport through earthen materials controls 222Rn releases to the atmosphere and to indoor environments. The key soil-related parameters characterizing 222Rn transport in earthen materials are the 222Rn diffusion coefficient and the soil air permeability. Simple correlations have been developed for predicting the 222Rn diffusion coefficient and the air permeability of soils based on fraction of water saturation, total porosity, and arithmetic mean particle diameter. Correlations are based on 1,073 diffusion coefficient measurements and 137 soil air permeability measurements. The geometric standard deviations between the correlation predictions and the measurements are 1.98 for the diffusion coefficients and 2.31 for the soil air permeabilities. PMID- 1856084 TI - Determination of uranium and thorium concentrations in unprocessed soil samples. AB - An assay technique that directly determines the amount of 238U and 232Th in unprocessed, bulk soil samples has been developed. In this technique, a sample consisting of a 125-mL plastic bottle full of contaminated, moist, unprocessed soil is irradiated with gamma rays from 57Co. Induced U and Th K alpha fluorescent x rays are detected using a high-purity intrinsic germanium planar detector. Because of sample irradiation geometry, the fluorescent x-ray peaks lie on top of a large Compton backscatter peak. Spectral data are first fit to a combination polynomial and ERFc-step-function background that is subtracted from the peak data. The remaining peak data are fit to a Voigt Profile to properly determine peak area. The Voigt Profile, which is the convolution of the Gaussian response of the detector system and the Lorentzian energy distribution of x rays, describes the spectral peak better than a simple Gaussian distribution. A mathematical point-node model of the source-target-detector system, which includes fluorescent x-ray production by singly scattered Compton gamma s, calculates the predicted x-ray peak area per Bq cm-3 of target contamination. Soil attenuation coefficients, which are measured for each sample, are used by the model to properly transport gamma s and x rays through the soil sample. The sample 238U and 232Th concentrations are then calculated by dividing the measured peak areas by the model-predicted peak areas per Bq cm-3. No "soil standards," no assumptions about progeny equilibrium, and no sample preparation are required for this technique. PMID- 1856085 TI - A general multiple-compartment model for the transport of trace elements through animals. AB - Multiple-compartment models employed in the analysis of trace element transport in animals are often based on linear differential equations which relate the rate of change of contaminant (or contaminant concentration) in each compartment to the amount of contaminant (or contaminant concentration) in every other compartment in the system. This has the serious disadvantage of mixing intrinsic physiological properties with the geometry of the animal. The basic equations on which the model presented here is developed are derived from the actual physical process under way and are capable of separating intrinsic physiological properties from geometry. It is thus expected that rate coefficients determined through this model will be applicable to a wider category of physiologically similar animals. A specific application of the model for the study of contamination of sheep--or indeed for any ruminant--is presented, and the temporal evolution of contaminant concentration in the various compartments of the animal is calculated. The application of this model to a system of compartments with changing geometry is also presented. PMID- 1856086 TI - Radioiodine speciation in the hot cell effluent gases of a radiopharmaceutical production facility. AB - In order to characterize the various chemical forms of airborne radioiodine species, grab-sampling measurements were conducted at the hot cell laboratory of a radiopharmaceutical production facility, using a selective-adsorbent-iodine filter system. Volatile radioiodine species were produced in the hot cell process which extracted the fission product 99Mo from the irradiated uranium target. The effluent gases were then released through the hot cell filter bank and the main filter bank. Two samplings were made, one at the inlet and one at the outlet of the hot cell filter bank. In comparison with other radioiodine isotopes detected, higher than expected concentrations of 132I were found, primarily in the form of organic iodide--an observation that could be explained by the beta decay of 132Te, the precursor of 132I, in the hot cell waste solution. The relative distribution of airborne 132I was considerably different from that of other iodine radioisotopes. An unexpected component of these distributions was radioiodine penetrating the silver zeolite filter and adsorbed on a triethylenediamine (TEDA) impregnated charcoal filter. PMID- 1856087 TI - Shielding a spectrum of workloads in diagnostic radiology. PMID- 1856088 TI - Radon levels in a high-rise apartment. PMID- 1856089 TI - Precision of alpha-track radon exposure estimates determined from field measurements. PMID- 1856090 TI - Multi-fractal nature of radioactivity deposition on soil after the Chernobyl accident. AB - Fractal analysis is introduced in the field of environmental health physics. In particular, it is applied to the complex and inhomogeneous deposition pattern of radioactivity after the Chernobyl accident. The patchiness of 137Cs hot spots is quantified by a fractal dimension as low as 1. The problem of finding hot spots that might be of health concern is discussed. PMID- 1856091 TI - Phosphorus-32 personnel monitoring in research institutions. PMID- 1856093 TI - Gould and Goldman: deadly deceit--a defense. PMID- 1856092 TI - Leukemias in Plymouth county, Massachusetts. PMID- 1856094 TI - Health issues of ultraviolet "A" sunbeds used for cosmetic purposes. A statement by the International Non-Ionizing Radiation Committee of the International Radiation Protection Association. PMID- 1856095 TI - Chernobyl consequences. PMID- 1856096 TI - Human growth hormone treatment: Henry Ford Hospital experience 1964-1990. AB - Treatment with human growth hormone (GH) at Henry Ford Hospital began in 1964 and has included 145 patients. A total of 68 patients were treated with extracted hormone and 77 with recombinant GH. The appearance of Creutzfeldt-Jakob disease, now five cases worldwide, in patients treated with extracted hormone abruptly stopped its use in the United States. The development of recombinant GH in 1985 has resulted in greater availability of treatment. Diagnostic criteria are now more liberal and certain patients without GH deficiency, i.e., those with the Turner syndrome, are now being successfully treated with GH. GH is expensive and its inappropriate use would have a major impact on health care costs. Indications for its use are not yet fully elucidated. PMID- 1856097 TI - Contemporary approach to thyroid disease emphasizing use of high-sensitivity thyrotropin assays. AB - Capabilities of new high-sensitivity immunoradiometric assays for thyroid stimulating hormone (TSH-IRMA) to distinguish among hypothyroid, euthyroid, and hyperthyroid subjects and patient groups with low TSH for nonthyroidal causes suggested an algorithmic approach (directed TSH) to the evaluation of patients with suspected thyroid disease. Utilizing the algorithm, a TSH-IRMA result outside normal limits (0.5 to 5.0 mU/L) generates follow-up tests on the same sample. The interpretation of thyroid function tests (TSH-IRMA, thyroxine, resin uptake, free thyroxine index) and associated studies in the context of different clinical settings is reviewed. The approach is a cost-effective and efficient utilization of laboratory services. PMID- 1856098 TI - Festschrift: in honor of Raymond C. Mellinger. PMID- 1856099 TI - A thyroid testing algorithm: results of a pilot study. AB - We conducted a pilot study to evaluate an algorithm for thyroid function testing consisting of initial serum thyrotropin values, measured by a sensitive immunoradiometric assay (TSH-IRMA), followed by a computer-directed decision to order further studies. We divided 216 outpatients according to their serum TSH IRMA values as follows: suppressed (less than 0.1 mU/L, group I); low (0.1 to 0.4 mU/L, group II); normal (0.5 to 5.0 mU/L, group III); and high (greater than 5.0 mU/L, group IV). Thyroxine (T4), resin uptake (RU), and free thyroxine index (FTI) tests on groups I, II, and IV revealed that T4 and RU were normal for most patients in all groups and FTI was normal in 80% of group I, 93.4% of group II, and 93.3% of group IV. All patients in group I were designated hyperthyroid from either an exogenous or endogenous source. All patients in group II were clinically euthyroid except one; 50% were taking either L-thyroxine or propylthiouracil and 50% had no identifiable thyroid disease. Patients in group IV were hypothyroid. Overall, TSH was more effective in detecting both hypothyroidism and hyperthyroidism than either serum T4, RU ratio, or both combined in FTI since results of these measures fell in the normal range for most patients in all groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856100 TI - An ambulatory approach to self-care of diabetes. AB - Managing the insulin-requiring diabetic patient in an ambulatory setting includes metabolic regulation of the diabetes and education in its self-care. Means of achieving these goals include structured group or one-on-one individualized sessions. Third party policies relating to ambulatory care are challenged and their need for fiscal support emphasized. During the coming decade, diabetic patients should 1) have access to ambulatory care programs for metabolic regulation and education in self-care, 2) expect third party support of these programs, and 3) heighten their own priorities on diabetes care to ensure quality management of their diabetes. PMID- 1856101 TI - Primary hyperparathyroidism and monoclonal gammopathy. AB - Coexistent primary hyperparathyroidism and monoclonal gammopathy, although rare, has been reported previously by a number of investigators. We report four patients with such an occurrence who were seen between 1976 and 1988. Another patient with primary hyperparathyroidism also had multiple myeloma and was in remission for 12 years. These patients represent approximately 1% of the 386 patients with primary hyperparathyroidism seen during the same 12-year period. Although several mechanisms have been proposed to explain this concurrence, we believe it is the result of a chance occurrence. A review of the literature, an estimate of the chance occurrence of coincidental monoclonal gammopathy, benign or malignant, in patients with primary hyperparathyroidism, and some practical implications of this interesting coexistence are presented. PMID- 1856102 TI - Disturbances in lipid metabolism associated with chylothorax and its management. AB - Changes in circulating lipid status were studied in a 70-year-old woman during management of chylothorax that included chest drainage, pleuroperitoneal shunting, and a successful thoracic duct ligation. Hypolipidemia with a relative decline in high-density lipoprotein (HDL) cholesterol was apparent at presentation. Following recovery, serum HDL cholesterol rose to the upper limit of normal. Apolipoprotein A-1 (Apo A-1) was discordantly raised during the period of pleuroperitoneal shunting. We speculate that diversion of chylomicrons to the liver with subsequent hydrolysis accounted for a release of Apo A-1 particles into the circulation at a time when the formation of HDL was compromised by a state of starvation. PMID- 1856103 TI - Chronic pancreatitis progressing to duodenal obstruction in the absence of classic symptoms. AB - We report the case of a 34-year-old alcoholic who was initially seen in March 1985 because of acute pancreatitis. A mass was demonstrated in the head of the pancreas. Serial sonogram and computed tomography scans over 4 1/2 years revealed progressive encroachment of the duodenum without symptoms attributable to obstruction. In 1989, three separate endoscopies with multiple biopsies showed chronic inflammation and strictures. Hypotonic duodenography confirmed stricture and obstructed duodenum. Surgical intervention is being considered. Duodenal obstruction secondary to chronic pancreatitis is rare. It may proceed subclinically for several years independent of continued alcohol use. Only when obstruction became severe in our patient did the classic symptoms of postprandial nausea, emesis, and weight loss become manifest. Obstructive jaundice from chronic pancreatitis due to stricture in the pancreatic portion of the common bile duct is uncommon. PMID- 1856104 TI - Nutrition support of HIV+ patients. AB - Case management strategies for the nutritional support of patients infected with the human immunodeficiency virus (HIV) are evolving as the disease becomes less rapidly fatal and more chronic. Nutritional status changes in advanced HIV infection are similar in many respects to protein-calorie malnutrition. Current clinical effort and research focuses on the beneficial effects of preserving lean body mass and keeping asymptomatic patients in good nutritional status by preventing micronutrient deficiencies and by treating preexisting nutritional problems rather than attempting to intervene late in the disease's course, after secondary malnutrition has already developed. Nutrition support and intervention trials only late in the disease process have not been promising in reversing weight loss once it has occurred. Special diets, such as lactose- or gluten-free diets, may be helpful in some cases as asymptomatic treatment of some opportunistic infections, and such measures may slow additional losses. However, secretory diarrhea, which often seems to be inherent to the disease itself, is not ameliorated by such measures. Current research is focusing on the potential role of glutamine in slowing malabsorption and on combinations of diet and drug treatments. Asymptomatic patients are now the focus of concern. Preserving good nutritional status by attention to preventing weight loss and loss of lean body mass and assuring food safety are primary. Symptomatic patients require specific assistance depending on the presence of opportunistic infections and the drugs required. Specific nutrition support measures depend on whether or not the gut is functional.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856105 TI - The phenomenology of Cushing's syndrome: one patient's account. AB - Cushing's syndrome caused by ectopic secretion of adrenocorticotropic hormone (ACTH) is often a serious disease and a diagnostic dilemma. In the reported patient, the source of ACTH proved to be a benign pulmonary carcinoid tumor. The patient describes his trying experiences through the six months from initial diagnosis to definitive therapy. PMID- 1856106 TI - Immunohistochemical localization of metallothionein in the eye of rats. AB - In order to elucidate possible physiological roles of metallothionein (MT), we have studied immunohistological localization of MT in the eye of the rat, using an avidin-biotin peroxidase complex method. As a result, strong MT immunostaining was observed in the epithelium of the lens and cornea. In the retina, considerably strong MT immunostaining was observed in the pigment cell layer while the nerve fiber layer and inner plexiform layer showed weak MT staining. Glial cells in the optic nerve were found to have marked MT staining. The present result is consistent with the hypothesis that MT may be involved not only in activation of zinc enzymes and cell proliferation through supply of zinc ions, but also in a protective mechanism in the blood-retina barrier. PMID- 1856107 TI - Changes in cell surface and intracellular glycoproteins of trophoblastic giant cells during mouse placentation. AB - Changes in lectin bindings of mouse trophoblastic giant cells (TGCs) were examined by light and electron microscopy. Neither Griffonia simplicifolia agglutinin (GS)-II nor succinyl-wheat germ agglutinin (s-WGA) bound to the 1st and 2nd TGCs on day 6.5 post coitum (p.c.), but did so from days 8.5 to 12.5 p.c. Positive reactions with s-WGA were localized in the perinuclear region and cell surface of both 1st and 2nd TGCs; while GS-II bound only to the perinuclear region, where it appeared as network-like deposits. This region was identified as well-developed Golgi lamellae by electron microscopy. Moreover, SDS-PAGE and lectin-blot analysis of the 1st TGCs indicated that the intensity of s-WGA and GS II bindings increased in the glycoproteins of approximately 43, 40, 37, and 26 kDa and in those of 43 and 38 kDa, respectively, during the 8.5th to 10.5th day p.c. The reaction with GS-I was detected on cell surface of both the 1st and 2nd TGCs on day 6.5 p.c. The reaction in the 1st TGCs was intensely positive throughout their development, whereas the reactivity decreased in the 2nd TGCs on day 10.5 p.c. and completely disappeared on day 12.5 p.c. The GS-I reaction in TGCs was more intense at the maternal side than at the embryonic side. These results suggest that certain Gal and/or GlcNAc glycoproteins on the cell surface and in Golgi lamellae of TGCs dynamically change from the 8.5th to 10.5th day p.c. in association with mouse placentation. PMID- 1856108 TI - Presence and localization of proteins immunologically related to erythrocyte protein 4.1 in human skin. AB - Analogues of human erythrocyte protein 4.1 have been examined in the human skin by immunochemical techniques using anti-human erythrocyte protein 4.1 antibodies. Immunoblot analysis revealed that human epidermis contains 4.1-like proteins of 80 kDa and 78 kDa that cross react with anti-protein 4.1 antibodies. Analysis with immunofluorescence microscopy revealed that the plasma membrane of the human epidermal keratinocyte was stained intensively in the basal cells, whereas spinous cells were moderately stained. It is noted that eccrine sweat gland cells and ductal cells were also stained in the peripheral cytoplasma. Taken together, these results demonstrate that 4.1-like proteins are present in human epidermal keratinocytes, eccrine sweat gland cells and ductal cells. The present findings enable us to suggest that a membrane skeletal protein lattice might exist in these cells. PMID- 1856109 TI - In situ hybridization study of chromogranin A and B mRNA in carcinoid tumors. AB - The distribution of the mRNAs for chromogranin A and B was analyzed by in situ hybridization with 35S-labeled oligonucleotide probes in formalin-fixed paraffin embedded carcinoid tumor tissues. All the 15 mid-gut carcinoid tumors examined contained both mRNAs for chromogranin A and B at high level in tumor cells. Sixteen of 18 bronchial carcinoid tumors but only 2 of 5 rectal carcinoid tumors expressed one or both species of chromogranin mRNAs. The same tendency was seen with the argyrophil reaction according to Grimelius where most of the mid-gut tumor cells were uniformly stained, while considerable variation in reactivity was seen in some of the bronchial and rectal carcinoid tumor cells. The sequential sections were stained with a monoclonal antibody against chromogranin A and a polyclonal antiserum which reacts with both chromogranins. The expression of the mRNA for chromogranin A on the carcinoid tumors was almost concordant with that of chromogranin B as well as with the chromogranin A protein, whereas almost all tumors stained positively with the polyclonal antibodies. Analyses of mRNA expression of chromogranin A before and after interferon therapy on 4 patients with mid-gut carcinoids indicated an inhibition at pre-translational level. In conclusion, the mRNAs for chromogranin A and B are good markers for the carcinoid tumors, especially of mid-gut origin. Fore-gut, mid-gut and rectal carcinoid tumors are different in their endocrine properties regarding the expression of the chromogranins. PMID- 1856110 TI - Presence of renin, angiotensinogen, angiotensin II in the lamb anterior pituitary gland: immunocytochemical study after cryoultramicrotomy. AB - The presence of renin, angiotensin I-converting enzyme and angiotensin II detected by immunocytochemistry in the adult male rat anterior pituitary has suggested the existence of a pituitary renin-angiotensin system. To establish another mammalian experimental model we have investigated the presence of renin, angiotensinogen, angiotensin I-converting enzyme, and angiotensin II II in five normal lamb anterior pituitaries by immunocytochemistry after cryoultramicrotomy. Renin, angiotensinogen and angiotensin II immunoreactivities were observed only in cytoplasmic granules of lactotrophs, and the three proteins were found co localized with prolactin in the same granules by double immunolabelling. No immunoreactive angiotensin I-converting enzyme was observed. These results suggest an activation of renin in the cytoplasmic granules of lactotrophs leading to a local synthesis of angiotensin II. Thus, the lamb anterior pituitary may provide a good experimental model for investigating the possible autocrine action of a local renin-angiotensin system on prolactin release in the human pituitary. PMID- 1856111 TI - Calcitonin gene-related peptide, enkephalin and serotonin coexist in neuroepithelial bodies of the respiratory tract of the red-eared turtle, Pseudemys scripta elegans. An immunocytochemical study. AB - The lungs of the red-eared turtle, Pseudemys scripta elegans, have been investigated by light-microscopical immunocytochemistry for serotonin (5-HT) and the neuropeptides calcitonin gene-related peptide (CGRP), enkephalin (ENK), bombesin, somatostatin, calcitonin and cholecystokinin. CGRP- or 5-HT-like immunoreactivity (LI) was demonstrated in neuroepithelial bodies (NEBs) and solitary neuroepithelial endocrine cells lying between the ciliated epithelial cells of the intrapulmonary bronchi, and of the primary, secondary and tertiary trabeculae. Furthermore, ENK-LI NEBs were found between the trabecular ciliated epithelial cells. No reaction was observed with antisera against bombesin, somatostatin, calcitonin, and cholecystokinin. Using consecutive sections, CGRP LI appears to be colocalized with 5-HT-LI in NEB cells. In addition, it was demonstrated that all the ENK-LI NEBs also contain CGRP-LI, whereas only a part of the CGRP-LI NEBs reveal ENK-LI. To our knowledge this is the first demonstration of CGRP- and/or ENK-LI in pulmonary NEBs of a lower vertebrate. PMID- 1856112 TI - Microphotometric determination of enzymes in brain sections. V. Glycerophosphate dehydrogenases. AB - An incubation medium was adapted for the microphotometric determination (kinetic and end-point measurements) of the activities of mitochondrial alpha glycerophosphate dehydrogenase (GPDH) in the rat hippocampus. For comparison, the activities of the cytoplasmic NAD-linked alpha-glycerophosphate dehydrogenase were also measured. The study showed that in the demonstration of both enzymes the use of an exogenous electron carrier is necessary. Both enzymes react to phenazine methosulfate (PMS) which transfers reduction equivalents to the electron acceptor nitroblue tetrazolium chloride (NBT), thus causing a coreaction of GPDH in the demonstration of NAD-GPDH. Therefore, only the NAD-independent GPDH which is stimulated by menadione, can be selectively demonstrated in the histochemical procedure applied. The final incubation medium of GPDH consisted of 15 mM L-glycerol 3-phosphate, 5 mM NBT, 0.4 mM menadione, 7.5% polyvinyl alcohol in 0.5 M Hepes buffer, pH 8; the final pH of the incubation medium was 7.5. A linear response of the reaction lasted about 5 min. There was a linear relationship between section thickness and the formation of reaction product up to a section thickness of 14 microns. The apparent Km value at 25 degrees C was 0.6 mM. It is concluded that using menadione histochemical methods are suited to determine the mitochondrial GPDH activities in brain sections whereas using PMS a coreaction of GPDH takes place in the demonstration of NAD-GPDH, so that a histochemical quantification of NAD-GPDH cannot be recommended. PMID- 1856115 TI - The psychophysiological development of freedom. Presidential address. PMID- 1856113 TI - Local cerebral glucose utilization in the brain of old, learning impaired rats. AB - The local cerebral glucose utilization (LCGU) was measured in 63 different cortical areas and nuclei of the telencephalon, diencephalon and rhombencephalon of young adult (3 to 4-month-old) rats and of 27-month-old Wistar rats, in which learning impairments had been proven by a water maze test. The LCGU was determined by [14C]2-deoxyglucose autoradiography. In the old rats the mean LCGU of all brain regions was significantly reduced by about 10% compared with the young control group; the mean LCGU was 74.2 mumol glucose/(100 g x min) in the young and 66.7 in the old rats. Different degrees of LCGU decrease were found in the different regions. Most of the brain regions with significantly reduced LCGU values in the aged, learning impaired rats were associated with auditory and visual functions, the dopaminergic system, and structures known to be involved in learning and memory processes. Therefore, the regional pattern of LCGU reduction found in the aged, learning impaired rats did not resemble any known pattern found after lesions of a single transmitter system or systemic administration of transmitter agonists or antagonists. PMID- 1856116 TI - Psychophysiology: where have we been, where are we going? Vice presidential address. PMID- 1856114 TI - Microphotometric determination of enzymes in brain sections. IV. Isocitrate dehydrogenases. AB - A polyvinyl alcohol-(PVA) containing incubation medium was adapted for the microphotometric determination (kinetic and end-point measurements) of the activities of NAD- and NADP-linked isocitrate dehydrogenases (ICDHs) in cryostat sections of the rat hippocampus. The following incubation medium is recommended for the quantification of NAD- and NADP- (differences in brackets) ICDHs: 100 mM DL-isocitrate, 10 mM sodium azide, 5 mM (4 mM) nitroblue tetrazolium (NBT), 7 mM NAD (4 mM NADP), 10 mM magnesium chloride, 0.25 mM phenazine methosulfate (PMS), with or without 5 mM ADP (without ADP), 23% PVA in 0.05 M Hepes buffer; the final pH was 7.5. With these incubation media a linear response of the reactions lasted at least 20 min. In kinetic and end-point measurements the same level of activities was demonstrable. The use of NaN3 (as a blocker of the respiratory chain) and PMS (as artificial electron carrier) was indispensible for the transfer of all reduction equivalents in the dehydrogenase reactions to the tetrazolium salt NBT. Furthermore, the activation by magnesium ions and the need of PVA to avoid diffusion artefacts of the loosely bound ICDHs were clearly shown. It is concluded that the quantification of ICDHs in situ could be a valuable tool for neurochemical investigations because ICDHs play a role not only in the substrate flux through the tricarboxylic acid cycle but also in providing alpha-ketoglutarate for the formation of glutamate which is an important amino acid in the brain. PMID- 1856117 TI - Psychophysiology in the changing world. Vice presidential address. PMID- 1856118 TI - Electrodermal differentiation of deception: perceived accuracy and perceived memorial content manipulations. AB - The demonstration of deception as a psychophysiological phenomenon requires a comparison of physiological responses to two conditions (experimental and control) which differ only with respect to deception. Such electrodermal (skin conductance response) differentiation was recently reported in the Differentiation of Deception paradigm, which controls for two potentially important sources of confounding in polygraph (often referred to as the Detection of Deception): differential question significance and differential frequency of question occurrence. The present study manipulated (between 32 subjects in a 2 x 2 design) two two-level, subjective factors in the paradigm: Perceived Accuracy of polygraphy (written and oral instructions characterising accuracy as high vs low) and Perceived Memorial Content (20 more complex, less personal, and less meaningful questions vs 6 less complex, more personal, and more meaningful questions). Significant differentiation of deception was again obtained, as was evidence for the effectiveness of the manipulations. However, the deception phenomenon was not clearly affected by either of the two subjective factors. In addition, one post-hoc test showed significantly increased differentiation under the low Perceived Accuracy condition, which is contrary to the widespread belief of polygraphers that high perceived accuracy is not only important but even essential for the detection of deception. However, the applied, polygraphic aim of detecting guilt in individuals is quite different from the scientific, psychophysiological aim of differentiating deception as a psychological process, and the phenomena involved probably have different causes. PMID- 1856119 TI - Traumatic malposition of the mandible: the essence of balanced occlusion. PMID- 1856120 TI - Mechanism of quinolone uptake into bacterial cells. PMID- 1856121 TI - Neurotoxicity of beta-lactam antibiotics: predisposing factors and pathogenesis. AB - Neurotoxic reactions caused by beta-lactam antibiotics occur frequently following direct application of antibiotic to the brain surface or into the cerebral cisterns. Epileptogenic reactions have also been observed after administration of very high systemic doses. There seem to be considerable differences in the neurotoxic potential of the various beta-lactams; benzylpenicillin, cefazolin and, lately, imipenem/cilastatin appear to be drugs with higher neurotoxic potential than other compounds. There is now strong evidence that the concentration of beta-lactam in the brain, and not that in the cerebrospinal fluid, is the decisive factor for the risk of neurotoxic reactions. Factors known to increase the risk of neurotoxicity are excessive doses, decreased renal function, damage to the blood-brain barrier, preexisting diseases of the central nervous system, old age and concurrent use of drugs that are nephrotoxic or that may lower the seizure threshold. Another factor that may be of importance is blockage of the transport system that is responsible for transport of beta lactams out of the central nervous system. PMID- 1856122 TI - Possible in-vivo transfer of beta-lactamase TEM-3 from Klebsiella pneumoniae to Salmonella kedougou. AB - Salmonella kedougou BM2659 was isolated from the stools and a blood culture of a patient and Klebsiella pneumoniae BM2657 and S. kedougou BM2658 were isolated later from the stools of the same patient. Strains BM2657 and BM2658 had identical resistance phenotypes, to beta-lactams, aminoglycosides and tetracycline, due to the presence of the same genes, blaT, aacA4 and tetC, respectively. Oligotyping indicating that beta-lactam resistance in these strains was encoded by blaT-3 and synthesis of TEM-3 was confirmed by isoelectric focusing. In BM2657 and BM2658, the resistance characters were located on Inc7 or M self-transferable plasmids with indistinguishable EcoRI and HindIII restriction patterns. Southern hybridization of plasmid DNA of these strains with probes pCFFO4, the prototype plasmid encoding TEM-3, genes blaT, aacA4 and tetC gave identical patterns. S. kedougou BM2658 and BM2659 had identical biotypes and serotypes but BM2659 was susceptible to all the study antibiotics. These observations suggest possible transfer, in the digestive tract, of a plasmid encoding TEM-3 beta-lactamase from K. pneumoniae BM2657 to S. kedougou BM2659. PMID- 1856123 TI - Characterization of beta-lactamases encoded by pathogenic strains of Escherichia coli from Portugal. AB - A survey of 2036 strains of Escherichia coli was conducted in Oporto, Portugal, to establish the prevalence of resistance to beta-lactam antibiotics. Isolates were from hospital and clinical practice patients, and were further divided into urinary and non-urinary pathogens. A high level of resistance to aminopenicillins (55.3%) was observed. Further examination of the resistant strains showed that the frequencies of occurrence of known beta-lactamases were as follows: TEM-1 (78.2% of resistant strains); SHV-1 (7.9%); TEM-2 (0.45%); OXA-1 (1.5%); HMS-1 (0.18%); TEM-1 + SHV-1 (4.2%). Other pairs of beta-lactamases were also identified in less than 2% of the resistant strains. In addition, 4.7% of the resistant strains produced elevated levels of a presumed chromosomal cephalosporinase, while 0.9% produced a ceftazimidase of pI 5.8-5.9 which was similar to TEM-6. PMID- 1856124 TI - Concomitant dissemination of three extended-spectrum beta-lactamases among different Enterobacteriaceae isolated in a French hospital. AB - From January 1988 to August 1989, 267 non-repetitive strains of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBla) derived from TEM (CTX-1/TEM-3, CAZ-6) or SHV (CAZ-5) were isolated from 219 colonized or infected patients. ESBlas were characterized by analytical isoelectric focusing. Biotypes, resistance phenotypes and plasmid patterns were determined in order to differentiate the isolates in each species. Among the 116 CTX-1-producing Enterobacteriaceae, 48 strains were differentiated: 27 from 74 Klebsiella pneumoniae isolates, seven from 22 Enterobacter aerogenes isolates, and 14 from a combined total of seven K. oxytoca, five Serratia marcescens, six Escherichia coli, 1 Enterobacter cloacae and 1 Citrobacter freundii. CAZ-5 has been isolated since January 1988 in 16 different strains among 101 K. pneumoniae isolates. CAZ 6 was first identified in K. pneumoniae (January 1988). Among the 48 Enterobacteriaceae producing CAZ-6, 12 strains were differentiated: four from 39 E. aerogenes isolates, three from four K. pneumoniae, and five from a combined total of two S. marcescens, two E. coli and one E. cloacae. During this outbreak, CTX-1 was found to be encoded by 85 kb (Inc 7/M) or greater than or equal to 150 kb (Inc 6/C) plasmids. CAZ-6 was always encoded by an 85 kb (Inc 7/M) plasmid and CAZ-5 by a greater than 150 kb plasmid. These results show that strain epidemics and plasmid dissemination occurred mainly in K. pneumoniae and E. aerogenes for CTX-1, in E. aerogenes for CAZ-6, and in K. pneumoniae for CAZ-5. They also suggest that the bla(tem) gene (CTX-1) has spread between different plasmids present in the same ecosystem. PMID- 1856125 TI - Antibacterial activity and penicillin-binding protein affinity of new cephalosporin derivatives in Staphylococcus aureus and Escherichia coli. AB - A series of C3-substituted cephalosporins with different levels of oxidation was synthesized and the activities of eight compounds, including affinity for penicillin-binding proteins (PBPs), in Staphylococcus aureus and Escherichia coli were studied. The more hydrophobic cephalosporins, with a thiophene moiety at the C7 position, were more active than C7-methoxyiminoaminothiazole derivatives against S. aureus H (beta-lactam-susceptible), and compounds with a thioether function at C3 were more active than those with a sulphonyl function at this position. In contrast, the most active compounds against E. coli were hydrophilic, zwitterionic C7-methoxyimino-aminothiazole C3-thioether cephalosporins. The physicochemical properties of the most active compounds were in accord with those predicted for rapid outer membrane penetration. However, among the thiophene cephalosporins the dianionic sulphonyl compounds were more active than the monoanionic thioether derivatives. There was a reasonably good correlation between MICs and PBP affinities for S. aureus H. The compounds had most affinity for PBP 1 and least for PBP 4. The two most potent compounds had high affinities for PBPs 1, 2 and 3. The compounds had low affinities for the beta-lactam-insensitive PBP 2a of methicillin-resistant S. aureus strain DU4916 K7. The novel cephalosporins had the highest affinities for PBPs 1a/1b and 3 of E. coli DCO. The major morphological response of E. coli to the compounds was cell elongation. PMID- 1856126 TI - Activity of clindamycin against Staphylococcus aureus and Staphylococcus epidermidis from four UK centres. AB - MICs of penicillin, methicillin, clindamycin, erythromycin, sodium fusidate and gentamicin were determined by an agar dilution method for 300 current isolates of Staphylococcus aureus and 100 of S. epidermidis, collected from four centres, and 38 stock strains of methicillin-resistant S. aureus (MRSA). All but one of the 300 current isolates of S. aureus were sensitive to clindamycin (MIC less than 0.5 mg/l), with an MIC90 of 0.12 mg/l. Of a total of 39 MRSA strains, 11 (28.2%) were resistant to clindamycin (MIC greater than 32 mg/l); all of these strains were also resistant to erythromycin. Ten of the 100 strains of S. epidermidis were resistant to clindamycin; they came from a reasonably equal geographical distribution and were also resistant to erythromycin. The results suggest that clindamycin might still be useful as a second-line agent for infections caused by S. aureus and S. epidermidis, although its activity against MRSA was limited to approximately two-thirds of the MRSA strains tested in this study. PMID- 1856127 TI - Antimicrobial effects of lomefloxacin in vitro. AB - The MIC of lomefloxacin was determined for 554 isolates from the urinary tract. Some of the more resistant strains of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, and Pseudomonas aeruginosa were studied in a dynamic in vitro model in order to study dosing strategies. The model simulated, in Mueller Hinton broth, the profile of plasma lomefloxacin concentrations in volunteers. Bacteria were exposed to a range of lomefloxacin concentration profiles achievable by oral dosing. The first dose of lomefloxacin was rapidly bactericidal in a dose-dependent manner for all strains. On re-exposure, a dose dependent inhibitory effect was observed. Drug-resistant mutants were readily isolated from all bacteria tested on lomefloxacin-containing plates. These occurred at a high frequency in P. aeruginosa (10(-1)), but less frequently in K. pneumoniae (10(-3)). P. mirabilis (10(-5)), and E. coli (10(-6)). The number of resistant mutants isolated tended to be lower with use of higher drug concentrations. The results suggest that lomefloxacin dosing regimens ensuring maintenance of a high serum concentration: MIC ratio will result in maximal antibacterial effects and minimal problems with resistant strains. PMID- 1856128 TI - Interactions in vitro between polyenes and imidazoles against yeasts. AB - The polyenes, amphotericin B and mepartricin and the imidazoles, miconazole, ketoconazole, itraconazole and fluconazole, were studied either alone or in paired polyene-imidazole combinations to determine their activity in vitro against clinical yeast isolates. The methods included shaken and standing liquid cultures, continuous cultures and chequerboard titrations, with or without the incorporation of pooled human plasma. The polyenes were found to exert an immediate cidal action even with high cell populations whereas the imidazoles demonstrated a time-dependent fungistatic activity which increased very slowly with increase in drug concentration. The interactions observed with the paired combinations were consistent and were found to be anomalous with all methods used. The activity of the imidazoles was enhanced by the presence of the polyenes; by contrast the polyenes were strongly antagonized by the imidazoles. PMID- 1856129 TI - The in-vitro activity of drugs against Blastocystis hominis. AB - The development of an assay to measure the sensitivity of drugs against Blastocystis hominis using the incorporation of 3H-hypoxanthine is described. The activity of 42 compounds have been measured. Four of the 5-nitroimidazoles tested (satranidazole, S75 0400 A, flunidazole and ronidazole) were found to be more active than metronidazole, the drug commonly used to treat infections caused by B. hominis in humans. Other potentially useful compounds include emetine, furazolidone and quinacrine. Ketoconazole and iodoquinol reported to have therapeutic activity in infections caused by this parasite were found to be significantly less active than metronidazole. PMID- 1856130 TI - Animal pharmacokinetics and interspecies scaling of FCE 22101, a penem antibiotic. AB - The pharmacokinetics of FCE 22101 were studied in rats, rabbits, Cynomolgus monkeys and dogs after intravenous administration. Pertinent pharmacokinetic parameters were determined according to a two-compartment model and correlated among species as an exponential function of body weight, thereby allowing an estimation of pharmacokinetic parameters corresponding to a 70 kg man. Allometric equations, including data on humans reported in the literature, were also established and used to study similarities and differences in the disposition of FCE 22101 among species. The pharmacokinetic profile of FCE 22101 was consistent with the principles of allometry in all animal species studied (and in man) with the exception of the Cynomolgus monkey, in which clearance of FCE 22101 was slower than expected. PMID- 1856131 TI - The dynamics of intraperitoneal growth and elimination of Escherichia coli and Bacteroides fragilis in porcine faecal peritonitis treated with fosfomycin. AB - The kinetics of intraperitoneal killing of proliferating bacteria was studied in pigs given fosfomycin. Eight animals were given intra-abdominal injection of Escherichia coli and Bacteroides fragilis (10(9) cfu of each species) mixed in sterile faces. Three hours later, half of the animals received an intravenous dose of 1 g fosfomycin (0.05 g/kg). Host defences rapidly decreased the density of E. coli in all animals in the first hour. After 2h, growth of E. coli started and continued throughout the experiment in pigs not receiving fosfomycin. B. fragilis was slowly eliminated in the first 5 6 h, then numbers increased in all animals. Fosfomycin caused a reduction in E. coli density, by 10(2.19) +/- 0.29 (mean +/- S.E.M.) cfu/ml, or more than 150 times within 1 h, while the concentration of B. fragilis was unaltered. After 10 h the difference in E. coli density between fosfomycin treated and untreated animals was 10(4.96) cfu/ml (P less than 0.01). Fosfomycin eradicated E. coli in faecal peritonitis but not B. fragilis, which is resistant in vitro. There was a prolonged elimination of the drug from peritoneal exudate in pigs infected with bacteria in sterile faeces compared to the elimination in uninfected pigs or pigs infected only with bacteria. PMID- 1856132 TI - Tissue distribution and bioactivity of amphotericin B administered in liposomes to cancer patients. AB - Amphotericin B concentration was measured by high-pressure liquid chromatography (HPLC) and by bioassay in tissues of 11 cancer patients who died from infection and/or their underlying disease after having received amphotericin B entrapped into sonicated liposomes (ampholiposomes). These concentrations were compared to those measured in 28 patients who had only received the commercially available preparation of amphotericin B-Na deoxycholate complex (Fungizone). The fungistatic and fungicidal titres of the tissue homogenates were also evaluated using two strains of Candida spp. and one strain of Cryptococcus neoformans to determine the bioactivity of amphotericin B incorporated in our liposomes. Tissue concentrations varied with the tested tissues and were correlated with the total dose of amphotericin B administered whether given as amphotericin B-Na deoxycholate or ampholiposomes. Amphotericin B concentrations measured by bioassay in tissue methanolic extracts reached 58-81% of concentrations measured by HPLC, whereas only 15-41% was recovered from the unextracted homogenates. Fungicidal titres were seldom measured in tissues, but fungistatic titres were observed and were linearly correlated with amphotericin B concentration measured by HPLC. These results were similar for the patients who received only amphotericin B-Na deoxycholate and for those who received both preparations (amphotericin B-Na deoxycholate and ampholiposomes). Our results suggest that the tissue distribution of amphotericin B is not significantly modified by the type of preparation (deoxycholate complex or liposomes) and that most of the tissue bound amphotericin B is not bioactive. However, higher daily doses of amphotericin B can be administered safely when incorporated in liposomes and therefore high tissue concentrations may be obtained more rapidly with ampholiposomes than with amphotericin B-Na deoxycholate. PMID- 1856133 TI - Centrifugation injury of gram-negative bacteria. PMID- 1856134 TI - Kinetics of antimicrobial activity of aztreonam/clavulanic acid (2:1) against Xanthomonas maltophilia. PMID- 1856135 TI - Multiresistant Salmonella typhi in Bangladesh. PMID- 1856136 TI - Penetration of cefuroxime into bronchial mucosa following oral administration of cefuroxime axetil. PMID- 1856137 TI - Synergistic interaction of antibiotics with nasal penetration to methicillin sensitive and methicillin-resistant Staphylococcus aureus. PMID- 1856138 TI - Failure of a combination of vancomycin and fusidic acid in a patient with staphylococcal infection. PMID- 1856139 TI - Once daily amikacin. Report of a meeting. PMID- 1856140 TI - Serum concentrations and safety of single daily dosing of amikacin in children undergoing bone marrow transplantation. AB - The serum concentrations and safety of single daily dosing of amikacin were studied in 16 episodes of fever and granulocytopenia in children undergoing bone marrow transplantation. Amikacin (20 mg/kg) was administered as a 20 min iv infusion once daily for 7 to 19 days; all patients received concomitant therapy with ceftazidime. Peak amikacin concentrations measured immediately after infusion on day 1 and 4 of therapy averaged 72.29 +/- 11.6 mg/l and 74.02 +/- 19.29 mg/l respectively. A slight but statistically significant increase 30 minute post-infusion concentrations was observed in most patients during therapy. Serum amikacin were less than 3 mg/l in all trough samples and within 6 h post infusion in most patients. A significant increase in serum creatinine was observed in one patient, who was also receiving cyclosporin A. Auditory function was evaluated in 10 patients and showed no changes. Although other drugs were added to cover Gram-positive or fungal pathogens, all patients survived. These data combined with the recent experience of single daily dose amikacin in adults supports further evaluation of novel dosage regimens of aminoglycosides in children. PMID- 1856141 TI - Efficacy and safety of amikacin in systemic infections when given as a single daily dose or in two divided doses. Scandinavian Amikacin Once Daily Study Group. AB - Two hundred and twenty patients with serious infections verified or suspected to be of Gram-negative aetiology were treated in an open randomized comparative multicentre trial with amikacin 15 mg/kg/day given either as a single dose or in two divided doses at 12-h intervals. Amikacin was administered as a short-term iv infusion. When additional therapy was considered necessary piperacillin or ampicillin was recommended. The trial continues and an interim report on data from the 12 participating Scandinavian hospitals is presented. One hundred and forty-four patients have been evaluated for efficacy and 213 patients for safety. There were no significant differences between the two dosage regimens regarding efficacy and safety. A satisfactory clinical response was recorded in 129 (90%) of the evaluable patients. One serious adverse reaction was seen in a patient in the once-daily group. This was ototoxicity which was superimposed on a long standing hearing defect possibly caused by previous streptomycin therapy. PMID- 1856142 TI - Empirical antimicrobial therapy with a single daily dose of ceftriaxone plus amikacin in febrile granulocytopenic patients: a pilot study. AB - The optimal management of fever in granulocytopenic patients remains controversial. This pilot study investigated the potential value of single daily doses of amikacin administered empirically with ceftriaxone in febrile granulocytopenic patients. None of the patients died as a result of infection or toxicity from the prescribed regimen. Serum concentrations failed to show drug accumulation. Modifications of empirical antimicrobial therapy were made at a similar rate to other conventional regimens. Vancomycin seemed to increase the incidence of nephrotoxicity. Overall, this pilot study suggests that empirical therapy with single daily doses of amikacin plus ceftriaxone is safe and effective and should be further investigated in a larger number of patients. PMID- 1856143 TI - Single daily dose amikacin in paediatric patients with severe gram-negative infections. AB - Twenty-five children with serious Gram-negative infections were treated in a prospective study with amikacin 20 mg/kg administered in a single daily dose as a 30 min iv infusion for 4 to 12 days. In nine cases the amikacin was combined with beta-lactam antibiotics. Escherichia coli were the most frequent bacteria isolated followed by K. pneumoniae, Providencia and Enterobacter spp. and Pseudomonas aeruginosa with MICs ranging from 1 to 16 mg/l. Mean (+/- S.D.) peak and trough concentrations of days 1 and 4 of therapy ranged from 49 +/- 13.5 to 53.6 +/- 13.4 mg/l and 6 + 1.4 to 7.7 +/- 4.1 mg/l respectively. All patients were clinically and bacteriologically cured. No significant adverse reactions were observed. The results suggest that administration of a single daily dose of 20 mg/kg amikacin should be considered practical and safe in children. Further studies are needed. PMID- 1856144 TI - Once daily dosing of aminoglycoside: one step forward. PMID- 1856145 TI - Influence of dosage schedule on renal cortical accumulation of amikacin and tobramycin in man. AB - The pathogenesis of aminoglycoside nephrotoxicity is directly related to the accumulation of drug within the renal cortex. To identify measures that might prevent aminoglycoside nephrotoxicity, we investigated the influence of various dosage regimens on the renal cortical accumulation of amikacin and tobramycin in man. Patients undergoing nephrectomy for a renal tumour with normal renal function and no proteinuria received (i) a single dose of either amikacin (15 mg/kg) or tobramycin (4.5 mg/kg) given iv over 30 min, or (ii) a 24-h continuous infusion of either drug or (iii) amikacin as two injections of 7.5 mg/kg or tobramycin as three injections of 1.5 mg/kg over the 24 h preceding nephrectomy. Serum aminoglycoside pharmacokinetics were examined and renal cortical tissue was sampled for drug determination at operation. A single injection yielded cortical concentrations of 115.4 +/- 21.8 and 68.9 +/- 30.3 mg/kg for amikacin and tobramycin, respectively. Tissue levels after continuous infusion were 171.7 +/- 42.9 and 100.0 +/- 30.0 mg/kg for amikacin and tobramycin, respectively. Two injections of 7.5 mg/kg amikacin resulted in renal cortical concentrations of 196.9 +/- 54.9 and three injections of 1.5 mg/kg tobramycin resulted in renal cortical concentration of 76.5 +/- 18 mg/kg. The AUC for the three dosage regimens was not significantly different for the two aminoglycosides indicating linear serum pharmacokinetics for these drugs. In the case of amikacin, a single injection resulted in significantly lower drug levels than did a continuous infusion or administration of the same dose over three injections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856146 TI - Pharmacokinetic and toxicological evaluation of a once-daily regimen versus conventional schedules of netilmicin and amikacin. AB - The safety and pharmacokinetics of netilmicin (6.6 mg/kg) and amikacin (14.5 mg/kg) once daily (od) have been compared to their corresponding conventional schedules thrice daily (tid), and twice daily (bd), in patients (20 per group) suffering from pelvic inflammatory disease. Sensitive criteria of early renal and auditory alterations, namely urinary excretion of phospholipids and audiometry over a wide frequency range (0.25-18 kHz), respectively, were used. The first criterion (phospholipiduria) was validated by an animal study which demonstrated that rats receiving poly-L-aspartic acid, which protects against gentamicin induced nephrotoxicity, are also protected against renal phospholipidosis and phospholipiduria caused by this antibiotic. On that basis, netilmicin od was better tolerated than netilmicin tid. Amikacin caused less phospholipiduria than netilmicin, and, given od, resulted in little increase over baseline (95% CI, 95 147% increase). Reduction in threshold by greater than or equal to 15 dB for frequencies between 10-18 kHz occurred in nine of 19 patients receiving netilmicin tid compared with three or four of 19 or 20 patients treated with netilmicin od or amikacin (od or bd). However, changes at lower frequencies (0.25 8 kHz) were infrequent with all regimens (from 0/19 to 2/20). In conclusion, these very sensitive tests of nephro- and oto-toxicity suggest that od dosing of amikacin or netilmicin is, if anything, safer than bd or tid dosing. PMID- 1856147 TI - Pharmacokinetic evaluation of single daily dose amikacin. AB - The pharmacokinetic parameters of amikacin given once daily were compared to those of amikacin given bd at different daily dosages. In adult patients, 'peak' serum concentrations (30 min after 30 min infusion) were linearly proportional to the dose given with the following equation:-'peak' = 4.23 (dose in mg/kg)-3.93 (r, 0.827; P less than 0.0001). Areas under curves were also proportional to the dose and were not affected by the schedule of administration (od or bd). Serum half-life was neither affected by the dose nor the schedule of administration. However, the half-life was approximately 3 h in adult patients with infections and was greater than 4 h in elderly patients. In multiple dose studies, no accumulation was observed either in children or adults. However, 'peak' serum concentrations increased slightly. New recommendations for therapeutic drug monitoring need to be formulated. PMID- 1856148 TI - The pharmacokinetic of amikacin in critically ill adult and paediatric patients: comparison of once- versus twice-daily dosing regimens. AB - The pharmacokinetic profile of amikacin was analysed by a two-compartment model in 100 critically-ill adult and paediatric patients with normal renal function. In addition the serum amikacin levels in 200 patients randomized to receive a once- or twice-daily dosing regimen are reported. The mean volume of distribution (Vdt) was 0.33 l/kg in the adult patients, 0.50 l/kg in patients 6 to 12 months of age and 0.58 l/kg in patients less than 6 months old. The elimination half life was prolonged, being 3.45, 2.86 and 5.02 h for the respective age groups (normal 2 h). The clearances dose/AUC) were 0.051, 0.068 and 0.063 l/h/kg respectively. Within each group of patients there was a large variation in the pharmacokinetic parameters, with the Vdt varying by a factor of 6 and the elimination half-life by a factor of 10. All patients receiving a once-daily dose of amikacin had therapeutic peak concentrations. In comparison, therapeutic concentrations were achieved in only 48% of adult and 44% of the paediatric patients receiving the twice-daily dosing regimen. Furthermore the amikacin trough concentrations were significantly higher in the patients who received a divided daily dose. As a consequence of the pharmacokinetic profile of amikacin in critically ill patients a once-daily dosing regimen may be more effective and less toxic than the conventional twice-daily dosing regimen. PMID- 1856149 TI - Clinical and bacteriological efficacy, and practical aspects of amikacin given once daily for severe infections. AB - In a multicentre non-randomized open prospective study, 124 patients hospitalized in medical infectious disease or intensive care units, with severe community and hospital-acquired bacterial infections were treated with 15 mg/kg body weight amikacin in a once-daily dose given as a 30 min iv infusion, combined with other antibiotics. Infections were bacteriologically proven in 101 patients. The clinical responses showed 83.1% primary success and 83.9% definitive cure predominantly in intensive care patients with hospital-acquired infections and pneumonia. Bacteriological eradication was achieved in 67.3%. Bacteria associated with true failures and colonizations were predominantly Pseudomonas, Acinetobacter and Staphylococcus spp. The risk of nephrotoxicity may be decreased with such a regimen of amikacin, but no conclusions could be drawn with regard to ototoxicity. In summary, a once-daily dosing regimen of amikacin 15 mg/kg is practical and probably efficacious and safe in severely infected patients. PMID- 1856150 TI - Murine fibrosarcoma clone established in defined medium. PMID- 1856151 TI - Malignant transformation of human keratinocytes during adaptation to autotrophy. PMID- 1856152 TI - Percoll centrifugation eliminates mold contaminants from cell cultures. PMID- 1856153 TI - Spontaneous development of functionally active long-term monocytelike cell lines from channel catfish. AB - During the course of studies involving the in vitro manipulation of channel catfish peripheral blood leukocytes, spontaneous proliferation was observed with unexpectedly high frequency. Propagation of these spontaneously proliferating cells has resulted in the development of long-term (greater than 11 mo.) cell lines which stain positively for nonspecific esterase and peroxidase, are phagocytic for latex beads, and morphologically resemble mammalian monocytes or macrophages. These long-term cell lines also exhibit two important additional functional features. First, induction with lipopolysaccharide results in the secretion of relatively high levels of catfish high and low molecular weight species of interleukin-1 active on channel catfish and mouse T cells, respectively. Second, these cell lines are efficient antigen-presenting cells to autologous peripheral blood leukocytes for antigen specific in vitro proliferative and antibody responses. This antigen-presenting function is blocked by inhibitors known to prevent antigen processing and presentation by mammalian monocytes. Allogeneic mixtures of cell line (used as antigen-presenting cells) and responding peripheral blood leukocytes, however, resulted in strong mixed leukocyte reaction but not in specific antibody responses. The availability of such cell lines should facilitate further studies on accessory cell functions in fish immune responses. PMID- 1856154 TI - Effects of aging in vitro on intracellular proteolysis in cultured rabbit lens epithelial cells in the presence and absence of serum. AB - Alterations in proteolytic capabilities have been associated with abnormalities in the aged eye lens, but in vivo tests of this hypothesis have been difficult to pursue. To simulate aging, we cultured cells from an 8-yr-old rabbit to early (population-doubling level 20 to 30) and late (population-doubling level greater than 125) passage. Long-lived (t1/2 greater than 10 h) and short-lived (t1/2 less than 10 h) intracellular proteins were labeled with [3H]leucine, and the ability of the cells to mount a proteolytic response to the stress of serum withdrawal was determined. For early passage cells, the average t1/2 of long-lived proteins in the presence and absence of serum was 62 and 39 h, respectively. For late passage cells, the average t1/2 of long-lived proteins in the presence and absence of serum was 58 and 43 h, respectively. The net increase in intracellular proteolysis in the absence of serum was 59 and 35% for early and late-passage cells, respectively. Thus, in vitro-aged rabbit lens epithelial cells amount only 60% the proteolytic response to serum removal shown in "younger" cells. The enhanced ability of early passage cells to respond to serum removal seems to involve lower homeostatic levels of proteolysis in the presence of serum and greater enhancement of proteolysis in the absence of serum. Less than 2% of the protein is in the pool of short-lived proteins. Rates of proteolysis of short lived proteins in the presence and absence of serum were indistinguishable. With respect to basal proteolytic rates in the presence of serum and ability to mount a proteolytic response upon serum withdrawal, these rabbit lens epithelial cells are similar to bovine lens epithelial cells and fibroblasts. PMID- 1856155 TI - Preparation of fibroblast-free cytotrophoblast cultures utilizing differential expression of the CD9 antigen. AB - The leukemia-associated antigen CD9 is present on a variety of normal cells, with apparent variable expression on normal human fibroblasts. In this study, we demonstrate by immunoperoxidase staining and direct binding studies that the CD9 antigen is uniformly expressed on normal human fibroblasts grown from first trimester and term placenta, embryonic fetal fibroblasts, and from human adult and fetal skin fibroblasts. Higher CD9 expression was present on fetal cells. CD9 antigen was not present on trophoblast. Over 99% of fibroblasts could be absorbed onto antibody to the CD9 antigen conjugated to magnetic beads. By applying this selective immunoadsorption of fibroblasts to term placental cytotrophoblast preparations, we demonstrated that fibroblast contamination could be nearly completely eliminated. This is a novel technique for purifying primary trophoblast cultures and may have wider applicability in cell culture of other cell types. PMID- 1856156 TI - Effect of anticoagulants in vitro on the viability of lymphocytes and content of free fatty acids in plasma. AB - These authors attempted to test the effect of anticoagulants on lymphocytes viability by reproducing the procedure used for lymphocyte isolation for various immunologic tests in which blood specimens are allowed to stay at room temperature for 2 h before lymphocytes are isolated. Blood was obtained with three different anticoagulants i.e. heparin, citrate, and CPDA (citrate, phosphate, dextrose, and adenine). Plasma was lyophilized and extracted with ethanol. Dried ethanol extracts were suspended in medium (RPMI 1640 + 10% fetal bovine serum) and incubated with a lymphocyte cell line (MOLT-4). After 24 h of incubation the viability of cells was examined. The following death rates of the cells were observed: heparin -63 +/- 4.6% (mean +/- SEM), citrate -27 +/- 6.7%, and CPDA 6.2 +/- 0.6% (P less than 0.0005). A significant correlation was found between these results and changes in the concentrations of free fatty acids in the extracts. These results emphasize the importance of choosing the right anticoagulant when the viability of lymphocytes is obligatory. PMID- 1856157 TI - A comparison of primary cultures of rat cerebral microvascular endothelial cells to rat aortic endothelial cells. AB - A method to culture rat cerebral microvascular endothelial cells (RCMECs) was developed and adapted to concurrently obtain cultures of rat aortic endothelial cells (RAECs) without subculturing, cloning, or "weeding." The attachment and growth requirements of endothelial cell clusters from isolated brain microvessels were first evaluated. RCMECs required fetal bovine serum to attach efficiently. Attachment and growth also depended on the matrix provided (fibronectin approximately laminin much greater than gelatin greater than poly-D-lysine approximately Matrigel greater than hyaluronic acid approximately plastic) and the presence of endothelial cell growth supplement and heparin in the growth medium. Non-endothelial cells are removed by allowing these cells to attach to a matrix that RCMECs attach to poorly (e.g., poly-D-lysine) and then transferring isolated endothelial cell clusters to fibronectin-coated dishes. These cell cultures, labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarboxyamine perchlorate (DiI-Ac-LDL) and analyzed using flow cytometry, were 97.7 +/- 2.6% (n = 6) pure. By excluding those portions designed to isolate brain microvessels, the method was adapted to obtain RAEC cultures. RAECs do not isolate as clusters and have different morphology in culture, but respond similarly to matrices and growth medium supplements. RCMECs and RAECs have Factor VIII antigen, accumulate DiI-Ac-LDL, contain Weibel-Palade bodies, and have complex junctional structures. The activities of gamma-glutamyl transferase and alkaline phosphatase were measured as a function of time in culture. RCMECs had higher enzymatic activity than RAECs. In both RCMECs and RAECs enzyme activity decreased with time in culture. The function of endothelial cells is specialized depending on its location. This culture method allows comparison of two endothelial cell cultures obtained using very similar culture conditions, and describes their initial characterization. These cultures may provide a model system to study specialized endothelial cell functions and endothelial cell differentiation. PMID- 1856158 TI - Intracellular mechanisms involved in basement membrane induced blood vessel differentiation in vitro. AB - The extracellular matrix, particularly basement membranes, plays an important role in angiogenesis (blood vessel formation). Previous work has demonstrated that a basement membranelike substrate (Matrigel) induces human umbilical vein endothelial cells to rapidly form vessel-like tubes (Kubota, et al., 1988; Grant et al., 1989b); however, the precise mechanism of tube formation is unclear. Using this in vitro model, we have investigated morphologic changes occurring during tube formation and the cytoskeletal and protein synthesis requirements of this process. Electron microscopy showed that endothelial cells attach to the Matrigel surface, align, and form cylindrical structures that contain a lumen and polarized cytoplasmic organelles. The cytoskeleton is reorganized into bundles of actin filaments oriented along the axis of the tubes and is located at the periphery of the cells. The addition of colchicine or cytochalasin D blocked tube formation, indicating that both microfilaments and microtubules are involved in this process. Cycloheximide blocked tube formation by 100%, indicating that the process also required protein synthesis. In particular, collagen synthesis seems to be required for tube formation because cis-hydroxyproline inhibited tube formation, whereas either the presence of ascorbic acid or the addition of exogenous collagen IV to the Matrigel increased tube formation. Our results indicate that endothelial cell attachment to Matrigel induces the reorganization of the cytoskeleton and elicits the synthesis of specific proteins required for the differentiated phenotype of the cells. PMID- 1856159 TI - Nucleotide sequence and characterization of the gene for secreted alkaline phosphatase from Lysobacter enzymogenes. AB - Lysobacter enzymogenes produces an alkaline phosphatase which is secreted into the medium. The gene for the enzyme (phoA) was isolated from a recombinant lambda library. It was identified within a 4.4-kb EcoRI-BamH1 fragment, and its sequence was determined by the chain termination method. The structural gene consists of an open reading frame which encodes a 539-amino-acid protein with a 29-residue signal sequence, followed by a 119-residue propeptide, the 281-residue mature phosphatase, and a 110-residue carboxy-terminal domain. The roles of the propeptide and the carboxy-terminal peptide remain to be determined. A molecular weight of 30,000 was determined for the mature enzyme from sodium dodecyl sulfate polyacrylamide gel electrophoresis. The amino acid sequence was compared with sequences available in the current protein data base, and a region of the sequence was found to show considerable homology with sequences in mammalian type 5 iron-containing purple acid phosphatases. PMID- 1856160 TI - Cloning, sequencing, and expression of the gene coding for bile acid 7 alpha hydroxysteroid dehydrogenase from Eubacterium sp. strain VPI 12708. AB - Southern blot analysis indicated that the gene encoding the constitutive, NADP linked bile acid 7 alpha-hydroxysteroid dehydrogenase of Eubacterium sp. strain VPI 12708 was located on a 6.5-kb EcoRI fragment of the chromosomal DNA. This fragment was cloned into bacteriophage lambda gt11, and a 2.9-kb piece of this insert was subcloned into pUC19, yielding the recombinant plasmid pBH51. DNA sequence analysis of the 7 alpha-hydroxysteroid dehydrogenase gene in pBH51 revealed a 798-bp open reading frame, coding for a protein with a calculated molecular weight of 28,500. A putative promoter sequence and ribosome binding site were identified. The 7 alpha-hydroxysteroid dehydrogenase mRNA transcript in Eubacterium sp. strain VPI 12708 was about 0.94 kb in length, suggesting that it is monocistronic. An Escherichia coli DH5 alpha transformant harboring pBH51 had approximately 30-fold greater levels of 7 alpha-hydroxysteroid dehydrogenase mRNA, immunoreactive protein, and specific activity than Eubacterium sp. strain VPI 12708. The 7 alpha-hydroxysteroid dehydrogenase purified from the pBH51 transformant was similar in subunit molecular weight, specific activity, and kinetic properties to that from Eubacterium sp. strain VPI 12708, and it reached with antiserum raised against the authentic enzyme on Western immunoblots. Alignment of the amino acid sequence of the 7 alpha-hydroxysteroid dehydrogenase with those of 10 other pyridine nucleotide-linked alcohol/polyol dehydrogenases revealed six conserved amino acid residues in the N-terminal regions thought to function in coenzyme binding. PMID- 1856161 TI - Genetic organization and regulation of a meta cleavage pathway for catechols produced from catabolism of toluene, benzene, phenol, and cresols by Pseudomonas pickettii PKO1. AB - Plasmid pRO1957 contains a 26.5-kb BamHI restriction endonuclease-cleaved DNA fragment cloned from the chromosome of Pseudomonas pickettii PKO1 that allows P. aeruginosa PAO1c to grow on toluene, benzene, phenol, or m-cresol as the sole carbon source. The genes encoding enzymes for meta cleavage of catechol or 3 methylcatechol, derived from catabolism of these substrates, were subcloned from pRO1957 and were shown to be organized into a single operon with the promoter proximal to tbuE. Deletion and analysis of subclones demonstrated that the order of genes in the meta cleavage operon was tbuEFGKIHJ, which encoded catechol 2,3 dioxygenase, 2-hydroxymuconate semialdehyde hydrolase, 2-hydroxymuconate semialdehyde dehydrogenase, 4-hydroxy-2-oxovalerate aldolase, 4-oxalocrotonate decarboxylase, 4-oxalocrotonate isomerase, and 2-hydroxypent-2,4-dienoate hydratase, respectively. The regulatory gene for the tbuEFGKIHJ operon, designated tbuS, was subcloned into vector plasmid pRO2317 from pRO1957 as a 1.3 kb PstI fragment, designated pRO2345. When tbuS was not present, meta pathway enzyme expression was partially derepressed, but these activity levels could not be fully induced. However, when tbuS was present in trans with tbuEFGKIHJ, meta pathway enzymes were repressed in the absence of an effector and were fully induced when an effector was present. This behavior suggests that the gene product of tbuS acts as both a repressor and an activator. Phenol and m-cresol were inducers of meta pathway enzymatic activity. Catechol, 3-methylcatechol, 4 methylcatechol, o-cresol, and p-cresol were not inducers but could be metabolized by cells previously induced by phenol or m-cresol. PMID- 1856162 TI - Identification of two genes, kpsM and kpsT, in region 3 of the polysialic acid gene cluster of Escherichia coli K1. AB - The polysialic acid capsule of Escherichia coli K1, a causative agent of neonatal septicemia and meningitis, is an essential virulence determinant. The 17-kb kps gene cluster, which is divided into three functionally distinct regions, encodes proteins necessary for polymer synthesis and expression at the cell surface. The central region, 2, encodes products required for synthesis, activation, and polymerization of sialic acid, while flanking regions, 1 and 3, are thought to be involved in polymer assembly and transport. In this study, we identified two genes in region 3, kpsM and kpsT, which encode proteins with predicted sizes of 29.6 and 24.9 kDa, respectively. The hydrophobicity profile of KpsM suggests that it is an integral membrane protein, while KpsT contains a consensus ATP-binding domain. KpsM and KpsT belong to a family of prokaryotic and eukaryotic proteins involved with a variety of biological processes, including membrane transport. A previously described kpsT chromosomal mutant that accumulates intracellular polysialic acid was characterized and could be complemented in trans. Results of site-directed mutagenesis of the putative ATP-binding domain of KpsT are consistent with the view that KpsT is a nucleotide-binding protein. KpsM and KpsT have significant similarity to BexB and BexA, two proteins that are essential for polysaccharide capsule expression in Haemophilus influenzae type b. We propose that KpsM and KpsT constitute a system for transport of polysialic acid across the cytoplasmic membrane. PMID- 1856163 TI - The Aeromonas hydrophila cphA gene: molecular heterogeneity among class B metallo beta-lactamases. AB - An Aeromonas hydrophila gene, named cphA, coding for a carbapenem-hydrolyzing metallo-beta-lactamase, was cloned in Escherichia coli by screening an Aeromonas genomic library for clones able to grow on imipenem-containing medium. From sequencing data, the cloned cphA gene appeared able to code for a polypeptide of 254 amino acids whose sequence includes a potential N-terminal leader sequence for targeting the protein to the periplasmic space. These data were in agreement with the molecular mass of the original Aeromonas enzyme and of the recombinant enzyme produced in E. coli, evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of crude beta-lactamase preparations followed by renaturation treatment for proteins separated in the gel and localization of protein bands showing carbapenem-hydrolyzing beta-lactamase activity by a modified iodometric technique. The deduced amino acid sequence of the CphA enzyme showed regions of partial homology with both the beta-lactamase II of Bacillus cereus and the CfiA beta-lactamase of Bacteroides fragilis. Sequence homologies were more pronounced in the regions encompassing the amino acid residues known in the enzyme of B. cereus to function as ligand-binding residues for the metal cofactor. The CphA enzyme, however, appeared to share a lower degree of similarity with the two other enzymes, which, in turn, seemed more closely related to each other. These results, therefore, suggest the existence of at least two molecular subclasses within molecular class B metallo-beta-lactamases. PMID- 1856164 TI - In vitro synthesis and O acetylation of peptidoglycan by permeabilized cells of Proteus mirabilis. AB - The synthesis and O acetylation in vitro of peptidoglycan by Proteus mirabilis was studied in microorganisms made permeable to specifically radiolabelled nucleotide precursors by treatment with either diethyl ether or toluene. Optimum synthesis occurred with cells permeabilized by 1% (vol/vol) toluene in 30 mM MgCl2 in in vitro experiments with 50 mM Tris-HCl buffer (pH 6.80). Acetate recovered by mild base hydrolysis from sodium dodecyl sulfate-insoluble peptidoglycan synthesized in the presence of UDP-[acetyl-1-14C]N-acetyl-D glucosamine was found to be radioactive. Radioactivity was not retained by peptidoglycan synthesized when UDP-[acetyl-1-14C]N-acetyl-D-glucosamine was replaced with both unlabelled nucleotide and either [acetyl-3H]N-acetyl-D glucosamine or [glucosamine-1,6-3H]N-acetyl-D-glucosamine. In addition, no radioactive acetate was detected in the mild base hydrolysates of peptidoglycan synthesized in vitro with UDP-[glucosamine-6-3H]N-acetyl-D-glucosamine as the radiolabel. Chasing UDP-[acetyl-1-14C]N-acetyl-D-glucosamine with unlabelled material served to increase the yield of O-linked [14C]acetate, whereas penicillin G blocked both peptidoglycan synthesis and [14C]acetate transfer. These results support the hypothesis that the base-labile O-linked acetate is derived directly from N-acetylglucosamine incorporated into insoluble peptidoglycan via N----O transacetylation and not from the catabolism of the supplemented peptidoglycan precursors followed by subsequent reactivation of acetate. PMID- 1856165 TI - Purification, characterization, and molecular cloning of S-adenosyl-L-methionine: uroporphyrinogen III methyltransferase from Methanobacterium ivanovii. AB - An S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase (SUMT) activity has been identified in Methanobacterium ivanovii and was purified 4,500-fold to homogeneity with a 38% yield. The enzyme had an apparent molecular weight of 58,200 by gel filtration and consisted of two identical subunits of Mr 29,000, as estimated by gel electrophoresis under denaturing conditions. The Km value for uroporphyrinogen III was 52 nM. The enzyme catalyzed the two C-2 and C-7 methylation reactions converting uroporphyrinogen III into precorrin-2. Unlike Pseudomonas denitrificans SUMT, the only SUMT characterized to date (F. Blanche, L. Debussche, D. Thibaut, J. Crouzet and B. Cameron, J. Bacteriol. 171:4222-4231, 1989), M. ivanovii SUMT did not show substrate inhibition at uroporphyrinogen III concentrations of up to 20 microM. Oligonucleotide probes from limited peptide sequence information were used to clone the corresponding gene. The encoded polypeptide showed more than 40% strict homology with P. denitrificans SUMT. The M. ivanovii SUMT structural gene is likely to be, as is P. denitrificans cobA, involved in corrinoid synthesis. PMID- 1856166 TI - RNase I*, a form of RNase I, and mRNA degradation in Escherichia coli. AB - A previously unreported endoRNase present in the spheroplast fraction of Escherichia coli degraded homoribopolymers and small RNA oligonucleotides but not polymer RNA. Like the periplasmic endoRNase, RNase I, the enzyme cleaved the phosphodiester bond between any nucleotides; however, RNase I degraded polymer RNA as fast as homopolymers or oligomers. Both enzymes migrated as 27-kDa polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and could not be separated by various chromatographic procedures. In rna insertion mutants, both enzymes were completely missing; the spheroplast enzyme is called RNase I*, since it must be a form of RNase I. The two forms could be distinguished by physical treatments. RNase I could be activated by Zn2+, while RNase I* was inactive in the presence of Zn2+. RNase I was inactivated very slowly at 100 degrees C over a wide pH range, while RNase I* was inactivated slowly by heat at pH 4.0 but much more rapidly as the pH was increased to 8.0. In the presence of a thiol-binding agent, the inactivation at the higher pH values was much slower. These results suggest that RNase I*, but not RNase I, has free sulfhydryl groups. RNase I* activity in the cell against a common substrate was estimated to be several times that of RNase I. All four 2',3' phosphomonoribonucleotides were identified in the soluble pools of growing cells. Such degradative products must arise from RNase I* activity. The activity would be suited for the terminal step in mRNA degradation, the elimination of the final oligonucleotide fragments, without jeopardizing the cell RNA. An enzyme with very similar specificity was found in Saccharomyces cerevisiae, suggesting that the activity may be widespread in nature. PMID- 1856167 TI - Sequence and transcriptional regulation of com101A, a locus required for genetic transformation in Haemophilus influenzae. AB - A 2.8-kb EcoRI-BglII fragment cloned from the wild-type Haemophilus influenzae Rd chromosome is shown to increase the transformability of the Com-101 mutant through trans complementation. Deletion and sequence analyses indicate that the active region of the clone carries a 687-bp open reading frame. A 0.3-kb insertion in the corresponding EcoRI-BglII fragment of the Com-101 chromosome is shown to be a partial (331-bp) duplication of this open reading frame. The wild type sequence produces a peptide of a size that is consistent with the sequence data when this sequence is expressed in Escherichia coli with a T7 promoter-based transcription vector. RNA hybridization analysis using a DNA probe derived from the open reading frame suggests that the sequence is transiently expressed during competence development. On the basis of these observations, it is proposed that the open reading frame corresponds to the com101A gene. PMID- 1856168 TI - Expression of the bop gene cluster of Halobacterium halobium is induced by low oxygen tension and by light. AB - The bop gene cluster consists of at least three genes: bop (bacterio-opsin), brp (bacterio-opsin-related protein), and bat (bacterio-opsin activator). We have quantitated transcript levels from these genes in a wild-type and bacterioruberin deficient mutant of Halobacterium halobium under conditions which affect purple membrane synthesis. In wild-type cultures grown under high oxygen tension in the dark, bop and bat transcript levels were low during steady-state growth and then increased approximately 29- and approximately 45-fold, respectively, upon entry into stationary phase. brp gene transcription remained very low and essentially unchanged under these conditions. In addition, exposure of wild-type cultures growing under high oxygen tension to 30,000 lx of light stimulated expression of all three genes, especially brp. In contrast to the wild-type, transcription from all three genes in the bacterioruberin mutant was very high during steady-state growth under high oxygen tension in the dark. Cultures of the bacterioruberin mutant were shifted at early stationary phase to low oxygen tension to determine whether oxygen concentrations lower than those present in stationary phase would induce transcription of the bop gene cluster in this strain. Indeed, transcription was induced, suggesting that the bop gene cluster is not completely uncoupled from regulation by oxygen tension in the bacterioruberin mutant. From these data, we propose a regulatory model involving two different mechanisms: (i) bat gene expression is induced under conditions of low oxygen tension and the bat gene product activates bop gene expression and (ii) light induces brp transcription, which stimulates or modulates bat transcription. PMID- 1856169 TI - Rifampin-resistant replication of pBR322 derivatives in Escherichia coli cells induced for the SOS response. AB - Replication of plasmid pBR322 in Escherichia coli cells normally requires RNA synthesis and thus is sensitive to rifampin, an inhibitor of RNA polymerase. In cells induced for the SOS response, however, derivatives of pBR322 were found to replicate in the presence of rifampin. This rifampin-resistant replication of pBR322 requires the insertion of certain sequences of DNA. The replication depends on recF+ and DNA polymerase I. PMID- 1856170 TI - Autoradiographic analysis of diaminopimelic acid incorporation in filamentous cells of Escherichia coli: repression of peptidoglycan synthesis around the nucleoid. AB - Peptidoglycan synthesis rate in nonconstricting filaments of Escherichia coli dnaX(Ts) has been studied by autoradiography of incorporated [3H]diaminopimelic acid. Analysis of autoradiograms of whole cells and sacculi showed that peptidoglycan is synthesized at a reduced rate in the nucleoid-containing parts of these filaments. The lower rate of peptidoglycan synthesis in the cell center coincides with a higher local rate of protein synthesis. DNA-less cell formation in dnaX(Ts), dnaX(Ts) sfiA, and the minB minicell-forming mutant is accompanied by a local increase in peptidoglycan synthesis at the constriction site. PMID- 1856171 TI - Role of two flagellin genes in Campylobacter motility. AB - Campylobacter coli VC167 T2 has two flagellin genes, flaA and flaB, which share 91.9% sequence identity. The flaA gene is transcribed from a o-28 promoter, and the flaB gene from a o-54 promoter. Gene replacement mutagenesis techniques were used to generate flaA+ flaB and flaA flaB+ mutants. Both gene products are capable of assembling independently into functional filaments. A flagellar filament composed exclusively of the flaA gene product is indistinguishable in length from that of the wild type and shows a slight reduction in motility. The flagellar filament composed exclusively of the flaB gene product is severely truncated in length and greatly reduced in motility. Thus, while both flagellins are not necessary for motility, both products are required for a fully active flagellar filament. Although the wild-type flagellar filament is a heteropolymer of the flaA and flaB gene products, immunogold electron microscopy suggests that flaB epitopes are poorly surface exposed along the length of the wild-type filament. PMID- 1856172 TI - The Vlp system of Mycoplasma hyorhinis: combinatorial expression of distinct size variant lipoproteins generating high-frequency surface antigenic variation. AB - Isogenic populations of Mycoplasma hyorhinis undergo in vitro high-frequency phase variation in the expression of surface lipoproteins; these products also vary markedly in size through changes in periodic protein structure (R. Rosengarten and K.S. Wise, Science 247:315-318, 1990). In this report, we rigorously define three distinct translation products comprising the Vlp (variable lipoprotein) system of M. hyorhinis SK76 and establish parameters of Vlp structural diversity and expression that distinguish the Vlp system from previously described examples of antigenic variation. VlpA, VlpB, and VlpC are prominent amphiphilic membrane lipoproteins characterized by detergent-phase fractionation and metabolic labeling with [35S]cysteine and [3H]palmitate. VlpA is distinguished from VlpB and VlpC by its selective labeling with [35S]methionine; VlpB and VlpC are distinguished by specific epitopes defined by surface-binding monoclonal antibodies (MAbs); a third MAb defines a surface epitope shared by VlpB and VlpC (but absent from VlpA). Each Vlp displays 12 to 30 spontaneous size variant forms comprising a periodic ladder that could also be generated by partial trypsin digestion of individual Vlp size variants. Different periodic intervals within VlpB and VlpC further distinguish these two products structurally. Mycoplasma colony opacity correlates inversely with Vlp size. Each Vlp undergoes independent, oscillating high-frequency phase variation in isogenic populations and can be expressed individually or concomitantly with other Vlps in a noncoordinate manner. All seven possible combinations of these three products were observed; however, no variants were found that lacked a Vlp. High-frequency size variation of each Vlp superimposed on combinatorial diversity in Vlp expression yields greater than 10(4) possible structurally distinct Vlp mosaics, of which 104 were documented along with 24 of 42 possible transitions among the seven Vlp combinations. In addition to these features, VlpA, VlpB, and VlpC were specifically recognized by serum antibodies from swine with experimental M. hyorhinis SK76-induced arthritis, indicating expression and immunogenicity of Vlps in the natural host. The structure and variation of Vlps and their known involvement in MAb-mediated modulation of mycoplasma-infected host cell properties and mycoplasma killing are discussed in relation to the surface architecture and adaptive potential of the wall-less mycoplasmas. PMID- 1856174 TI - Relationships among the rfb regions of Salmonella serovars A, B, and D. AB - The O antigens of Salmonella serogroups A, B, and D differ structurally in their side chain sugar residues. The genes encoding O-antigen biosynthesis are clustered in the rfb operon. The gene rfbJ in strain LT2 (serovar typhimurium, group B) and the genes rfbS and rfbE in strain Ty2 (serovar typhi, group D) account for the known differences in the rfb gene clusters used for determination of group specificity. In this paper, we report the nucleotide sequence of 2.9 kb of DNA from the rfb gene cluster of strain Ty2 and the finding of two open reading frames which have limited similarity with the corresponding open reading frames of strain LT2. These two genes complete the sequence of the rfb region of group D strain Ty2 if we use strain LT2 sequence where restriction site data show it to be extremely similar to the strain Ty2 sequence. The restriction map of the rfb gene cluster in group A strain IMVS1316 (serovar paratyphi) is identical to that of the cluster in strain Ty2 except for a frameshift mutation in rfbE and a triplicated region. The rfb gene clusters of these three strains are compared, and the evolutionary origin of these genes is discussed. PMID- 1856173 TI - Cloning, mapping, and characterization of the Escherichia coli prc gene, which is involved in C-terminal processing of penicillin-binding protein 3. AB - The prc gene, which is involved in cleavage of the C-terminal peptide from the precursor form of penicillin-binding protein 3 (PBP 3) of Escherichia coli, was cloned and mapped at 40.4 min on the chromosome. The gene product was identified as a protein of about 80 kDa in maxicell and in vitro systems. Fractionation of the maxicells producing the product suggested that the product was associated with the periplasmic side of the cytoplasmic membrane. This was consistent with the notion that the C-terminal processing of PBP 3 probably occurs outside the cytoplasmic membrane: the processing was found to be dependent on the secY and secA functions, indicating that the prc product or PBP 3 or both share the translocation machinery with other extracytoplasmic proteins. DNA sequencing analysis of the prc gene region identified an open reading frame, with two possible translational starts 6 bp apart from each other, that could code for a product with a calculated molecular weight of 76,667 or 76,432. The prc mutant was sensitive to thermal and osmotic stresses. Southern analysis of the chromosomal DNA of the mutant unexpectedly revealed that the mutation was a deletion of the entire prc gene and thus that the prc gene is conditionally dispensable. The mutation resulted in greatly reduced heat shock response at low osmolarity and in leakage of periplasmic proteins. PMID- 1856175 TI - The bent-end morphology of Treponema phagedenis is associated with short, left handed, periplasmic flagella. AB - Treponema phagedenis Kazan 5 is a spirochete with multiple periplasmic flagella attached near each end of the cell cylinder. Dark-field microscopy revealed that most of the cell is right-handed (helix diameter, 0.23 micron; helix pitch, 1.74 microns), and the ends appear bent. These ends could move and gyrate while the central part of the cell remained stationary. The present study examines the basis for the bent-end characteristic. Motility mutants deficient in periplasmic flagella were found to lack the bent ends, and spontaneous revertants to motility regained the periplasmic flagella and bent-end characteristic. The length of the bent ends (2.40 microns) was found to be similar to the length of the periplasmic flagella as determined by electron microscopy (2.50 microns). The helix diameter of the bent ends was 0.57 micron, and the helix pitch of the bent ends was 1.85 microns. The periplasmic flagella were short relative to the length of the cells (15 microns) and, in contrast to the reports of others, did not overlap in the center of the cell. Similar results were found with T. phagedenis Reiter. The results taken together indicate that there is a causal relationship between the bent-end morphology and the presence of short periplasmic flagella. We report the first three-dimensional description of spirochete periplasmic flagella. Dark field microscopy of purified periplasmic flagella revealed that these organelles were left-handed (helix diameter, 0.36 microns; helix pitch, 1.26 microns) and only 1 to 2 wavelengths long. Because of a right-handed cell cylinder and left handed periplasmic flagella along with bent ends having helix diameters greater than those of either the cell cylinder or periplasmic flagella, we conclude that there is a complex interaction of the periplasmic flagella and the cell cylinder to form the bent ends. The results are discussed with respect to a possible mechanism of T. phagedenis motility. PMID- 1856176 TI - Extracellular lipase of Pseudomonas sp. strain ATCC 21808: purification, characterization, crystallization, and preliminary X-ray diffraction data. AB - A procedure for the purification of a very hydrophobic lipase from Pseudomonas sp. strain ATCC 21808 was elaborated by avoiding the use of long-chain detergents in view of subsequent crystallization of the enzyme. The purification procedure included chromatography on Q-Sepharose in the presence of n-octyl-beta-D glucopyranoside, Ca2+ precipitation of fatty acids, and Octyl-Sepharose chromatography. The enzyme was purified 260-fold to a yield of 35% and a specific activity of 3,300 U/mg. The molecular weight was determined as 35,000; a polyacrylamide gel under nondenaturing conditions revealed a band at 110,000, and the isoelectric point proved to be at 4.5 to 4.6. The lipase crystallized with different salts and ethylene glycol polymers in the presence of n-octyl-beta-D glucopyranoside and one alkyloligooxyethylene compound (CxEy) in the range from C5E2 to C8E4. The crystals diffract to a resolution of about 0.25 nm. Precession photographs revealed that they belong to space group C2 with lattice constants of a = 9.27 nm, b = 4.74 nm, c = 8.65 nm, and beta = 122.3 degrees, indicating a cell content of one molecule per asymmetric unit of the crystal. In hydrolysis of triglycerides, the lipase showed substrate specificity for saturated fatty acids from C6 to C12 and unsaturated long-chain fatty acids. Monoglycerides were hydrolyzed very slowly. The N-terminal sequence is identical to that of the lipase from Pseudomonas cepacia. Treatment with diethyl-p-nitrophenylphosphate affected the activities toward triolein and p-nitrophenylacetate to the same extent and with the same velocity. PMID- 1856177 TI - Identification and localization of major stage-specific polypeptides of infectious Holospora obtusa with monoclonal antibodies. AB - With the help of monoclonal antibodies (MAbs) we investigated the occurrence of six polypeptides throughout parts of the life cycle of Holospora obtusa, a bacterium infecting the macronucleus of the ciliate Paramecium caudatum. The polypeptides of interest formed major bands in the protein pattern of the infectious form (IF) of H. obtusa. All MAbs used recognized individual polypeptide bands of the IF proteins separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Three polypeptides were also detected in the reproductive form in trace amounts. Two-dimensional electrophoresis revealed that the 33,000-, 28,000-, and 14,000-Mr polypeptides wre acidic and exhibited multiple isoelectric points under native conditions. Four polypeptides (Mrs of 50,000, 33,000, 28,000, and 20,000) were no longer detected or became drastically reduced within the first 30 min of invasion. Concomitantly, a loss of electron dense periplasmic material occurred, which is typical for invading IFs (H.-D. Gortz and M. Wiemann, J. Protistol. 24:101-109, 1989). In an attempt to clarify the subcellular localization of the six polypeptides, we performed chloroform extraction studies and identified four of the released polypeptides with MAbs. A 14,000-Mr polypeptide was immunocytochemically localized in the periplasm of the IF. The results showed that the six major polypeptides of the IF were stage specific or stage specifically enriched and are likely to contribute to the electron-dense periplasmic material of the IF. PMID- 1856178 TI - Mutational analysis and characterization of the Escherichia coli hya operon, which encodes [NiFe] hydrogenase 1. AB - Deletion mutants of Escherichia coli specific for hydrogenase isoenzyme 1 (HYD1) have been constructed and characterized. The hya operon, which contains genes for the two HYD1 structural subunits and four additional genes, was mapped at 22 min on the E. coli chromosome. The total hydrogenase activities of the HYD1-negative mutant and wild-type strains were similar. However, the formate dehydrogenase activity associated with the formate hydrogen lyase pathway was lower in the mutant. The hya mutant (strain AP1), complemented with only the hydrogenase structural genes (hyaAB), produced antigenically identifiable but inactive HYD1 protein. The first five genes of hya (hyaA to hyaE) were required for the synthesis of active HYD1, but wild-type levels of HYD1 activity were restored only when mutant cells were transformed with all six genes of the operon. When AP1 was complemented with hya carried on a high-copy-number plasmid, the HYD1 structural subunits were overexpressed, but the excess protein was unprocessed and localized in the soluble fraction of the cell. The products of hyaDEF are postulated to be involved in the processing of nascent structural subunits (HYAA and HYAB). This processing takes place only after the subunits are inserted into the cell membrane. It is concluded that the biosynthesis of active HYD1 is a complex biochemical process involving the cellular localization and processing of nascent structural subunits, which are in turn dependent on the insertion of nickel into the nascent HYD1 large subunit. PMID- 1856179 TI - The malX malY operon of Escherichia coli encodes a novel enzyme II of the phosphotransferase system recognizing glucose and maltose and an enzyme abolishing the endogenous induction of the maltose system. AB - Mutants lacking MalK, a subunit of the binding protein-dependent maltose maltodextrin transport system, constitutively express the maltose genes. A second site mutation in malI abolishes the constitutive expression. The malI gene (at 36 min on the linkage map) codes for a typical repressor protein that is homologous to the Escherichia coli LacI, GalR, or CytR repressor (J. Reidl, K. Romisch, M. Ehrmann, and W. Boos, J. Bacteriol. 171:4888-4899, 1989). We now report that MalI regulates an adjacent and divergently oriented operon containing malX and malY. MalX encodes a protein with a molecular weight of 56,654, and the deduced amino acid sequence of MalX exhibits 34.9% identity to the enzyme II of the phosphototransferase system for glucose (ptsG) and 32.1% identity to the enzyme II for N-acetylglucosamine (nagE). When constitutively expressed, malX can complement a ptsG ptsM double mutant for growth on glucose. Also, a delta malE malT(Con) strain that is unable to grow on maltose due to its maltose transport defect becomes Mal+ after introduction of malI::Tn10 and the plasmid carrying malX. MalX-mediated transport of glucose and maltose is likely to occur by facilitated diffusion. We conclude that malX encodes a phosphotransferase system enzyme II that can recognize glucose and maltose as substrates even though these sugars may not represent the natural substrates of the system. The second gene in the operon, malY, encodes a protein of 43,500 daltons. Its deduced amino acid sequence exhibits weak homology to aminotransferase sequences. The presence of plasmid-encoded MalX alone was sufficient for complementing growth on glucose in a ptsM ptsG glk mutant, and the plasmid-encoded MalY alone was sufficient to abolish the constitutivity of the mal genes in a malK mutant. The overexpression of malY in a strain that is wild type with respect to the maltose genes strongly interferes with growth on maltose. This is not the case in a malT(Con) strain that expresses the mal genes constitutively. We conclude that malY encodes an enzyme that degrades the inducer of the maltose system or prevents its synthesis. PMID- 1856180 TI - Cloning and characterization of a glutamine transport operon of Bacillus stearothermophilus NUB36: effect of temperature on regulation of transcription. AB - We cloned and sequenced a fragment of the Bacillus stearothermophilus NUB36 chromosome that contains two open reading frames (ORFs) whose products were detected only in cells of cultures grown in complex medium at high temperature. The nucleotide sequence of the two ORFs exhibited significant identity to the sequence of the glnQ and glnH loci of the glutamine transport system in enteric bacteria. In addition, growth response to glutamine, sensitivity to the toxic glutamine analog gamma-L-glutamylhydrazide, and glutamine transport assays with parental strain NUB3621 and mutant strain NUB36500, in which the ORF1 coding segment in the chromosome was interrupted with the cat gene, demonstrated that glnQ and glnH encode proteins that are active in the glutamine transport system in B. stearothermophilus. The inferred promoter for the glnQH operon exhibited a low homology to the -35 and -10 regions of the consensus promoter sequences of Bacillus subtilis and Escherichia coli genes. In addition, the inferred promoter for the glnQH operon also exhibited a low homology with the consensus promoter sequence deduced from the sequences of the promoters of nine different genes from B. stearothermophilus. Transcription of the glnQH operon was activated in a nitrogen-rich medium at high temperature and inhibited under the same conditions at low temperature. Transcription of the glnQH operon was partially activated in a nitrogen-poor medium at low temperature. The region upstream from glnQ contains sequences that have a low homology with the nitrogen regulator I-binding sequences and the nitrogen-regulated promoters of enteric bacteria. The effect of temperature on the regulation of the glnQH operon is discussed. PMID- 1856181 TI - Temperature-induced protein synthesis in Bacillus stearothermophilus NUB36. AB - Cultures of Bacillus stearothermophilus subjected to a temperature shift-up or shift-down of 15 degrees C within the normal temperature range of growth (45 to 65 degrees C) enter a transient adaptation period before exponential growth at the new temperature. The de novo synthesis of some proteins coincides with the adaptation period. PMID- 1856182 TI - Oxygen-dependent catabolism of indole-3-acetic acid in Bradyrhizobium japonicum. AB - Some strains of Bradyrhizobium japonicum have the ability to catabolize indole-3 acetic acid (IAA). Examination of this catabolism in strain 110 by in vivo experiments has revealed an enzymatic activity catalyzing the degradation of IAA and 5-hydroxy-indole-3-acetic acid. The activity requires addition of the substrates for induction and is oxygen dependent. The highest activity is obtained when the concentration of inducer is 0.2 mM. Spectrophotometric data are consistent with the suggestion that the indole ring is broken during degradation of IAA. We hypothesize that the enzyme catalyzes an oxygen-consuming opening of the indole ring analogous to the one catalyzed by tryptophan 2,3-dioxygenase. The pattern of metabolite usage by known tryptophan-auxotrophic mutants and studies of metabolites by high-performance liquid chromatography indicate that anthranilic acid is a terminal degradation product in the proposed pathway. PMID- 1856183 TI - Role of translation of the pheA leader peptide coding region in attenuation regulation of the Escherichia coli pheA gene. AB - In Escherichia coli, the expression of the pheA gene is regulated by attenuation of transcription. To study the molecular details of pheA attenuation, we introduced mutations in the pheA leader peptide coding region and analyzed their effects by using pheA promoter-lacZ gene transcription fusions (pheAp-lacZ). Mutations in the ribosome-binding site (pheAe1213) or in the translation initiation codon (pheAe24) of the pheA leader peptide coding region resulted in superattenuation of pheA expression. However, the presence of a stop codon upstream to the tandem phenylalanine codons (pheAe3334) led to an increase in the basal-level expression of pheA. This increase was further enhanced in the presence of prfA release factor mutant. The level of pheA expression in all three mutants was the same when cells were starved for phenylalanine. These results demonstrate that efficient translation of the pheA leader peptide coding region and the position of the ribosome on the leader transcript play decisive roles in the attenuation regulation of pheA. PMID- 1856184 TI - Cytochrome P-450. Multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms. PMID- 1856185 TI - Direct determination of free fatty acid transport across the adipocyte plasma membrane using quantitative fluorescence microscopy. AB - Movement of free fatty acids (FFA) across the plasma membrane has been directly measured for the first time, using fluorescent FFA analogs and quantitative fluorescence microscopy. The rate of short chain FFA (less than or equal to 12 carbons) transport from the extracellular medium into intracellular lipid droplets of 3T3F442A adipocytes was more than 40-fold faster than long chain FFA (16 and 18 carbons). The membrane-impermeable amino reagent 4,4' diisothiocyanostilbene-2,2'-disulfonate, inhibited greater than or equal to 50% of the long chain FFA transport but had no effect on short chain FFA transport. Oleic acid (2 microM) inhibited 90% of the fluorescent oleate transport but had no effect on the 11-carbon analog. These results indicate that a large fraction of long chain FFA uptake is mediated by a plasma membrane protein (s). PMID- 1856186 TI - Evidence that type II 5'-deiodinase is not a selenoprotein. AB - Brain type II 5'-iodothyronine deiodinase and liver type I 5'-iodothyronine deiodinase activities are decreased in rats fed a Se(2+)-deficient diet suggesting that both enzymes are Se(2+)-dependent proteins. Since serum thyroxine (T4) concentrations are twice normal in the Se(2+)-deficient animals, it is unclear whether the Se2+ deficiency or the increased circulating T4 account for the decrease in the brain enzyme. In order to separate these two possibilities, the effects of Se2+ on 5'-deiodinase in glial cells (type II) and LLC-PK1 cells (type I) were examined. LLC-PK1 and glial cells were grown in serum-free defined medium containing 0, 1 pM, 10 nM, and 40 nM Se2+ for 3-5 days or in medium containing 75Se2+ for 24 h. Deiodinase isozymes were determined by measuring catalytic activity and by quantification of the BrAc[125I]T4 affinity-labeled substrate binding subunits. Se2+ deficiency was confirmed by measuring the activity of the selenoprotein, glutathione peroxidase. Se2+ caused a concentration-dependent increase in glutathione peroxidase activity in both cell types, as well as in the type I enzyme, but had no effect on the type II enzyme. LLC-PK1 cells contained multiple 75Se(2+)-labeled proteins including the 27-kDa substrate binding subunit of the type I 5'-deiodinase. Glial cells contained seven 75Se(2+)-labeled proteins ranging in size from 12 to 62 kDa, none of which corresponded to the type II substrate binding subunit. these data show that, unlike the type I enzyme, the type II enzyme does not contain a selenocysteine or selenomethionine, further emphasizing the differences between these two isozymes. PMID- 1856187 TI - Evidence for a tetrahedral intermediate complex during serpin-proteinase interactions. AB - Proteinase inhibitors in the serpin family form complexes with serine proteinases by interactions between the gamma-OH group at serine 195 of the enzyme and a specific peptide bond within the reactive site loop of the inhibitor. However, the type of complex formed (i.e. Michaelis, acyl, or tetrahedral) is unknown. Until now, 13C NMR spectroscopy studies have only been useful in examining complexes formed with either peptide-related or small protein inhibitors, where 13C-labeled amino acids can be inserted semi-synthetically. Recombinant DNA technology has, however, made it possible to specifically enrich larger proteins with 13C. In the case of serpins we have examined the structure of the complex formed between human alpha 1-proteinase inhibitor uniformally labeled with [13C]methionine and porcine pancreatic elastase. 13C NMR spectroscopic studies revealed a large upfield chemical shift of the carbonyl signal of Met-358 upon complex formation suggesting for the first time that a tetrahedral adduct is formed between a serpin inhibitor and a serine proteinase. PMID- 1856188 TI - Acyl carrier protein-derived sequence encoded by the chloroplast genome in the marine diatom Cylindrotheca sp. strain N1. AB - The chloroplast genome of chromophytic and rhodophytic algae differs from the plastid genome of plants and green algae in that it encodes the gene for the small subunit (rbcS) of ribulose 1,5-bisphosphate carboxylase/oxygenase. Hybridization studies indicated that there was a second region of chloroplast DNA from the marine diatom Cylindrotheca sp. strain N1 that strongly hybridized to a previously isolated Cylindrotheca fragment that contained the rbcS gene and flanking sequences. Subsequent determination of the oligonucleotide sequence of this second chloroplast DNA fragment, however, indicated that hybridization was due to identical sequences 3' to the previously cloned Cylindrotheca chloroplast rbcL rbcS genes. Sequences derived from the 5' end of the second chloroplast DNA fragment contained a short open reading frame of 80 amino acids which was found to be highly homologous to bacterial acyl carrier protein and nuclear-encoded acyl carrier protein from plants. Amino acid residues in the environment of Ser 36 of the Escherichia coli protein, which is bound to a 4'-phosphopantetheine moiety, are virtually identical in the Cylindrotheca deduced sequence and all other sources of this protein. Unlike plant acyl carrier-deduced amino acid sequences, there was no leader peptide sequence found for the presumptive Cylindrotheca protein, consistent with the location of this DNA fragment on the chloroplast genome of this organism. DNA encoding the putative acyl carrier protein gene and rbcS thus represent two genes that are chloroplast-encoded in the chromophytic marine diatom Cylindrotheca, a significant departure from the organization of such genes in plants. PMID- 1856189 TI - Human lysosomal alpha-glucosidase. Characterization of the catalytic site. AB - The substrate analogue conduritol B epoxide (CBE) is demonstrated to be an active site-directed inhibitor of human lysosomal alpha-glucosidase. A competitive mode of inhibition is obtained with glycogen as natural and 4-methylumbelliferyl-alpha D-glucopyranoside as artificial substrate. The inactivation of the enzyme is time and concentration dependent and results in the covalent binding of CBE. Catalytic activity is required for binding to occur. CBE-labeled peptides containing the catalytic residue of lysosomal alpha-glucosidase were isolated and identified by microsequencing and amino acid analysis. The peptides appeared to originate from a protein domain which is highly conserved among alpha-amylases, maltase, glucoamylases, and transglucanosylases. Based on the sequence similarity and the mechanism of CBE binding, Asp-518 is predicted to be the essential carboxylate in the active site of lysosomal alpha-glucosidase. The functional importance of Asp 518 and other residues around the catalytic site was studied by expression of in vitro mutagenized alpha-glucosidase cDNA in transiently transfected COS cells. Substitution of Asp-513 by Glu-513 is shown to interfere with the posttranslational modification and the intracellular transport of the alpha glucosidase precursor. The residues Trp-516 and Asp-518 are demonstrated to be critical for catalytic function. PMID- 1856190 TI - Isolation and characterization of a succinimide variant of methionyl human growth hormone. AB - Deamidation of asparagine and glutamine residues, isomerization of aspartic acid side chains, and racemization of the L- to the D-form of the amino acids are common spontaneous chemical reactions known to occur in proteins. Previous studies have implicated succinimides as intermediates in these reactions; however, the evidence has been indirect. Our results demonstrate, for the first time, the presence of a succinimide intermediate in an intact protein. The succinimide (cyclic imide) variant was isolated from thermally stressed recombinant methionyl human growth hormone (hGH) by high performance anion exchange chromatography, further purified by reversed-phase high performance liquid chromatography, and analyzed by tryptic mapping. A later eluting tryptic peptide, compared with the native T12 peptide (residues 128-134, Leu-Glu-Asp-Gly Ser-Pro-Arg), was analyzed by mass spectrometry (MS). This variant had a protonated molecular mass of 755.3 atomic mass units (u), as compared with 773.3 u for the native T12 peptide. A difference of 18 u, a loss of water, is consistent with the formation of a succinimide intermediate at Asp-130 of methionyl hGH. MS/MS analysis of the cyclic imide-containing peptide verified that the modification occurred at Asp-130. A difference of 18 u was also observed for the intact cyclic imide methionyl hGH variant (22,238 u), as measured by electrospray mass spectrometry, compared with native methionyl hGH (22,256 u). PMID- 1856191 TI - Synaptotagmin II. A novel differentially distributed form of synaptotagmin. AB - Synaptotagmin is a synaptic vesicle membrane protein with properties suggestive of a role in synaptic vesicle exocytosis (Perin, M. S., Fried, V. A., Mignery, G. A., Jahn, R., and Sudhof, T. C. (1990) Nature 345, 260-263). Here, we report the structure of a novel form of synaptotagmin named synaptotagmin II that is highly homologous to the originally described synaptotagmin, now referred to as synaptotagmin I. Synaptotagmins I and II exhibit the same overall structure, containing a small intravesicular sequence that is glycosylated, a single transmembrane region, and a large carboxyl-terminal cytoplasmic sequence that includes two copies of an internal repeat homologous to the regulatory region of protein kinase C. The homology between synaptotagmins I and II is not uniformly distributed across the molecule but is highest in their carboxyl-terminal regulatory repeats (88% sequence identity) and lowest in their amino-terminal intravesicular sequences (46% sequence identity). RNA blots demonstrate complementary patterns of expression for synaptotagmins I and II, with synaptotagmin I preferentially expressed in rostral, phylogenetically younger brain regions, and synaptotagmin II predominantly expressed in caudal, phylogenetically older brain regions. With this description of two forms of synaptotagmin, all major synaptic vesicle proteins implicated in membrane traffic have now been shown to be present in several isoforms with differential distributions, suggesting that this is a general organizational principle of the mammalian brain. PMID- 1856192 TI - Time-dependent biphasic regulation of Na+/K+/Cl- cotransport in rat glomerular mesangial cells. AB - Time-dependent regulation of loop diuretic-sensitive Na+/K+/Cl- cotransport and [3H]bumetanide binding was investigated in cultured rat glomerular mesangial cells. Angiotensin II or epidermal growth factor induced stimulation of Na+/K+/Cl cotransport within 5 min, with a return to the control values by 30 min. Treatment of cells with phorbol 12-myristate 13-acetate (0.1 microM) (PMA), the calcium ionophore A23187 (1 microM), or the combination of 5 mM NaF and 10 microM AlCl3 produced a transient stimulation of Na+/K+/Cl- cotransport in 5-10 min to 148, 135, and 163% of control, respectively, which was followed by a progressive decrease to 34, 64, and 20% of the base-line activity, respectively, by 60 min. Exposure to cyclic 8-bromo-AMP (0.1 mM) or to forskolin (1 microM) and isobutylmethylxanthine (0.1 mM) caused a maximal inhibition of the cotransport in 5 min to 79 and 60% of control, respectively, with a subsequent gradual increase to 137 and 164% of the base-line activity, respectively, by 60 min. The effects of PMA, forskolin, and cyclic 8-bromo-AMP were concentration-dependent. In order to characterize further the alterations in the cotransport activity, binding of [3H]bumetanide was determined. Saturation binding analyses showed that the late inhibition of the cotransport by PMA and stimulation by forskolin were associated with a significant decrease and increase, respectively, in Bmax, with no significant changes in binding affinity. Correlations between changes in the cotransport activity and [3H]bumetanide binding were also observed in cells treated with cyclic 8-bromo-AMP or with NaF and AlCl3. Incubation of cells in Cl- or Na+ free solution greater than or equal to 60 min resulted in an increase in both the cotransport activity and [3H]bumetanide binding. These observations indicate that, in glomerular mesangial cells, persistent stimulation of second messengers that regulate the cotransporter induces a time-dependent, biphasic regulation of Na+/K+/Cl- cotransport and that the regulation occurring after greater than or equal to 60 min of treatment is primarily due to changes in the number of the active cotransport sites. Because long term removal of the transported ions also increases the number of active cotransport sites, these results suggest that alterations in intracellular ionic homeostasis may also mediate cotransport activity. PMID- 1856193 TI - Determination of disulfide bond pairs and stability in recombinant tick anticoagulant peptide. AB - Tick anticoagulant peptide (TAP) is a potent and selective inhibitor of blood coagulation factor Xa (Waxman, L., Smith, D.E., Arcuri, K.E., and Vlasuk, G.P. (1990) Science 248, 593-596). The 60-amino acid sequence of TAP shows limited homology to Kunitz-type inhibitors, including cysteines at positions 5, 15, 33, 39, 55, and 59. For detailed biochemical and pharmacological studies, a recombinant version of TAP (rTAP) has been produced in yeast. To determine the arrangement of the disulfide bonds, rTAP was cleaved with trypsin and chymotrypsin and the purified peptides sequenced using a gas-phase sequenator. The positions of the disulfide bonds were assigned by identifying the cycle(s) at which di-phenylthiohydan-toin-cystine was released. The specific disulfide bridges, Cys-5 to Cys-59, Cys-15 to Cys-39, and Cys-33 to Cys-55, are analogous to those in the prototype Kunitz-type inhibitor, bovine pancreatic trypsin inhibitor (BPTI). While treatment of BPTI with dithiothreitol rapidly and specifically reduced one disulfide bond, the reduction of disulfide bonds in rTAP proceeded at a slower rate and appeared to be nonspecific, reaching a maximum of two disulfides reduced. Reduced rTAP derivatized with either iodoacetic acid or iodoacetamide lost 59% of its inhibitory activity. In contrast, BPTI alkylated with iodoacetic acid inhibited trypsin half as well as the iodoacetamide derivative. Although the arrangement of disulfides in the two inhibitors is the same, their susceptibility to reduction is markedly different. PMID- 1856194 TI - Identification of active site residues of Escherichia coli fumarate reductase by site-directed mutagenesis. AB - Menaquinol-fumarate oxidoreductase of Escherichia coli is a four-subunit membrane bound complex that catalyzes the final step in anaerobic respiration when fumarate is the terminal electron acceptor. The enzyme is structurally and catalytically similar to succinate dehydrogenase (succinate-ubiquinone oxidoreductase) from both procaryotes and eucaryotes. Both enzymes have been proposed to contain an essential cysteine residue at the active site based on studies with thiol-specific reagents. Chemical modification studies have also suggested roles for essential histidine and arginine residues in catalysis by succinate dehydrogenase. In the present study, a combination of site-directed mutagenesis and chemical modification techniques have been used to investigate the role(s) of the conserved histidine 232, cysteine 247, and arginine 248 residues of the flavorprotein subunit (FrdA) in active site function. A role for His-232 and Arg-248 of FrdA is shown by loss of both fumarate reductase and succino-oxidase activities following site-directed substitution of these particular amino acids. Evidence is also presented that suggests a second arginine residue may form part of the active site. Potential catalytic and substrate-binding roles for arginine are discussed. The effects of removing histidine-232 of FrdA are consistent with its proposed role as a general acid base catalyst. The fact that succinate oxidation but not fumarate reduction was completely lost, however, might suggest that alternate proton donors substitute for His-232. The data confirm that cysteine 247 of FrdA is responsible for the N ethylmaleimide sensitivity shown by fumarate reductase but is not required for catalytic activity or the tight-binding of oxalacetate, as previously thought. PMID- 1856195 TI - Unassisted refolding of urea unfolded rhodanese. AB - In vitro refolding after urea unfolding of the enzyme rhodanese (thiosulfate:cyanide sulfurtransferase, EC 2.8.1.1) normally requires the assistance of detergents or chaperonin proteins. No efficient, unassisted, reversible unfolding/folding transition has been demonstrated to date. The detergents or the chaperonin proteins have been proposed to stabilize folding intermediates that kinetically limit folding by aggregating. Based on this hypothesis, we have investigated a number of experimental conditions and have developed a protocol for refolding, without assistants, that gives evidence of a reversible unfolding transition and leads to greater than 80% recovery of native enzyme. In addition to low protein concentration (10 micrograms/ml), low temperatures are required to maximize refolding. Otherwise optimal conditions give less than 10% refolding at 37 degrees C, whereas at 10 degrees C the recovery approaches 80%. The unfolding/refolding phases of the transition curves are most similar in the region of the transition, and refolding yields are significantly reduced when unfolded rhodanese is diluted to low urea concentrations, rather than to concentrations near the transition region. This is consistent with the formation of "sticky" intermediates that can remain soluble close to the transition region. Apparently, nonnative structures, e.g. aggregates, can form rapidly at low denaturant concentrations, and their subsequent conversion to the native structure is slow. PMID- 1856196 TI - A genetic approach for analyzing the pathway of LamB assembly into the outer membrane of Escherichia coli. AB - Results presented in this study demonstrate that a mutation which inserts an additional tyrosine between the 2 tyrosines at residues 118 and 119 of mature LamB protein results in a temperature-dependent assembly defect. This defect leads to the accumulation of an intermediate at the restrictive temperature that is most likely an assembly-defective monomer. These monomers are rapidly degraded in the wild type (htrA+) strain, and the biphasic kinetics of this degradation indicate that the mutation affects the assembly process and not the final product, i.e. stable trimers. In addition, our data show that the temperature dependent assembly defect in the mutant strain is reversible, and therefore the accumulated monomers represent a true assembly intermediate. Fractionation studies show that the monomers, which can be accumulated in htrA (degP) mutants at the restrictive temperature, are associated with the outer membrane, indicating that trimerization of LamB is not a prerequisite for localization. PMID- 1856197 TI - Expression and processing of mouse proopiomelanocortin in bovine adrenal chromaffin cells. A model system to study tissue-specific prohormone processing. AB - Many neuroendocrine precursor proteins, such as proopiomelanocortin (POMC), are cleaved in a tissue specific manner at distinct pairs of basic amino acids. Elucidating the specificity of the prohormone endoprotease(s) is essential to understanding cleavage specificity. However, isolation of these enzymes has been difficult, due to the inability to distinguish authentic maturation enzyme from the many other trypsin-like activities present in tissue homogenates. Recently, a "signature" of the insulin cell endoprotease(s) was defined in vivo by assessing the processing of a series of mutant cleavage sites in a model prohormone, mouse POMC (mPOMC) (Thorne, B. A., and Thomas, G. (1990) J. Biol. Chem. 265, 8436-8443. To investigate mechanisms of tissue-specific processing, we sought to identify the endoprotease signature of a cell having a processing phenotype distinct from insulinoma cells. In this report, the cleavage site specificity of the endoprotease(s) expressed in bovine adrenal chromaffin cells is examined. High levels of mPOMC (1.6 pmol/10(6) cells) were expressed in these cells using a vaccinia virus vector, and the precursor was targeted to the regulated secretory pathway. Analysis of POMC-derived peptides revealed that chromaffin cells processed the prohormone to a set of peptides highly similar to anterior pituitary corticotrophs, including adrenocorticotropin hormone (ACTH) and beta lipotropin, gamma-lipotropin, and beta-endorphin. This processing contrasted with the pattern of cleavage site utilization in Rin m5F insulinoma cells, which more closely resembled that of the intermediate pituitary melanotrophs. However, the processing preference for the sequences of pairs of basic amino acids (as tested using the entire series of mutant cleavage sites; -LysArg- (native), -ArgArg-, ArgLys-, -LysLys-, -HisArg-, -MetArg- at the ACTH/beta-lipotropin junction and LysLys- (native), -LysArg-, -ArgArg-, -ArgLys- in beta-endorphin) was the same in both insulinoma and adrenal chromaffin cells, suggesting recognition and cleavage by similar enzymes in both cell types. The cell-specific processing of mPOMC may thus result from expression of a common core set of processing enzymes and factors unique to each cell type affecting the enzyme accessibility to precursor cleavage sites. PMID- 1856198 TI - Identification of a nucleotide-binding site on glycoprotein IIb. Relationship to ADP-induced platelet activation. AB - Formalin-fixed platelets have been used to study the binding of adenine nucleotides in order to avoid the complications of nucleotide metabolism and to achieve steady-state binding. Sp-adenosine-5'-(1-thiotriphosphate) (Sp-ATP-alpha S) binds to platelets at two sites (Kd1 3 nM; 31,000 sites/platelet; Kd2 200 nM; 300,000 sites/platelet) as compared with values for ADP under these conditions (Kd1 30 nM; 25,000 sites/platelet and Kd2 3 microM; 400,000 sites/platelet) (bound/total approximately 0.1). Competition binding experiments showed that both of the ATP-alpha-S sites were accessible to ADP and vice versa. [35S]ATP-alpha-S was photoaffinity cross-linked to unfixed platelets by direct irradiation with ultraviolet light. A single radiolabeled component (120 kDa) was identified and shown to be identical with the alpha subunit of GPIIb based on two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blotting with anti-GPIIb monoclonal antibodies, by isoelectric focusing (pI 4.5 5.5), by immunoaffinity adsorption using monoclonal anti-GPIIb/IIIa antibodies coupled to Sepharose, and by crossed immunoelectrophoresis. Amino-terminal sequencing of a tryptic fragment labeled with [35S]ATP-alpha-S identified an 18 kDa domain beginning at Tyr-198 in the primary sequence of GPIIb alpha. These studies demonstrate the presence of an adenine nucleotide-binding site on GPIIb alpha. PMID- 1856199 TI - Secretion of the cell surface lipoprotein pullulanase in Escherichia coli. Cooperation or competition between the specific secretion pathway and the lipoprotein sorting pathway. AB - The fatty acid-acylated enzyme pullulanase is normally found in either of two locations in Escherichia coli, depending on whether or not the producing strains also express the genes specifically required for the second step in pullulanase secretion. When they are expressed, the enzyme is localized to the cell surface, while in their absence, it is directed to an unidentified location in the cell envelope which, upon lysis, forms vesicles whose density is intermediate between those of outer and cytoplasmic membrane vesicles. In order to test the role of the putative lipoprotein sorting signal, Asp2, in pullulanase sorting and secretion, the structural gene (pulA) was subjected to site-directed mutagenesis. Replacement of the Asp2 residue by Asn, Glu, or Ser caused the enzyme to fractionate with outer membrane-derived vesicles rather than with intermediate density vesicles from E. coli cells devoid of pullulanase secretion genes. A pronounced secretion defect was observed in a two-step secretion assay in which the first (sec gene-dependent) and second (pul gene-dependent) secretion steps were uncoupled. We propose that the Asp residue increases the efficiency of pullulanase secretion by allowing the enzyme to be initially sorted to a region of the cell envelope wherein most of the pullulase-specific secretion factors are located. PMID- 1856200 TI - Determination of binding constants for cooperative site-specific protein-DNA interactions using the gel mobility-shift assay. AB - We have investigated the question of whether the gel mobility-shift assay can provide data that are useful to the demonstration of cooperativity in the site specific binding of proteins to DNA. Three common patterns of protein-DNA interaction were considered: (i) the cooperative binding of a protein to two sites (illustrated by the Escherichia coli Gal repressor); (ii) the cooperative binding of a bidentate protein to two sites (illustrated by the E. coli Lac repressor); and (iii) the cooperative binding of a protein to three sites (illustrated by the lambda cI repressor). A simple, rigorous, and easily extendable statistical mechanical approach to the derivation of the binding equations for the different patterns is presented. Both simulated and experimental data for each case are analyzed. The mobility-shift assay provides estimates of the macroscopic binding constants for each step of ligation based on its separation of liganded species by the number of ligands bound. Resolution of the binding constants depends on the precision with which the equilibrium distribution of liganded species is determined over the entire range of titration of each of the sites. However, the evaluation of cooperativity from the macroscopic binding constants is meaningful only for data that are also accurate. Some criteria that are useful in evaluating accuracy are introduced and illustrated. Resolution of cooperative effects is robust only for the simplest case, in which there are two identical protein binding sites. In this case, cooperative effects of up to 1,000-fold are precisely determined. For heterogeneous sites, cooperative effects of greater than 1,000-fold are resolvable, but weak cooperativity is masked by the heterogeneity. For three-site systems, only averaged pair-wise cooperative effects are resolvable. PMID- 1856201 TI - Isolation of digoxin-like immunoreactive factors from mammalian adrenal cortex. AB - Endogenous digoxin-like immunoreactive factors (DLIF) are present in serum and tissues of humans and animals. To date, a tissue source for these factors has not been rigorously defined nor have these factors been isolated to identifiable homogeneity. In this study, we define the distribution of DLIF in mammalian tissues, demonstrate the adrenal cortex to be the principal source of this factor in bovine, and isolate DLIF to chromatographic homogeneity using high performance liquid chromatography (HPLC). DLIF concentrations in tissue extracts from rats measured as follows: adrenal glands, 44.3; serum, 6.3; liver, 5.2; kidney, 1.2; heart, brain, or lungs, less than 1.4 ng of digoxin-equivalent per g of protein. Human tissues showed similar results. In dogs, the ratio of the DLIF concentration in lumbar vein serum to that in infrarenal inferior vena cava serum was 3.3 +/- 0.4 (mean +/- S.E., n = 4). Bovine adrenal cortex contained 7 times more DLIF per g of tissue than the adrenal medulla. 70 +/- 4% (n = 7) of the total bovine cortical DLIF activity (6,159 pg of digoxin-equivalent) applied to a reverse phase HPLC column eluted as one definitive fraction. 60% of the digoxin like immunoreactivity extracted from bovine serum also co-eluted with DLIF from adrenal. None of the 14 steroid molecules or 7 cardiac glycoside congeners co eluted with the major DLIF activity. Our data indicate that 947 pmol of DLIF is equivalent to 1 pmol of digoxin-equivalent immunoreactivity. Preliminary mass spectral analysis suggests that purified DLIF has a molecular mass of 780 daltons comprised of one 390-dalton aglycone component plus several sugar moieties. This study establishes a definitive link between DLIF in serum and the adrenal cortex as a source tissue. We also demonstrate a method for purifying DLIF to chromatographic homogeneity with an extraction capacity of 1.2 nmol of DLIF per g of adrenal cortex. PMID- 1856202 TI - Remodeling of rat hepatocyte phospholipids by selective acyl turnover. AB - Acyl turnover of rat hepatocyte phospholipids and triacylglycerols was assessed by incubating the cells in media containing 40% H2(18)O and measuring the time dependent incorporation of 18O into ester carbonyls by gas chromatography-mass spectrometry of hydrogenated methyl esters. Incorporation of 18O into 22-carbon acyl groups was low in phosphatidylcholine, phosphatidylinositol, and phosphatidylserine, whereas in phosphatidylethanolamine, it was about the same as in the other acyl groups. Incorporation of 18O into individual molecular species of phosphatidylcholine and phosphatidylethanolamine was determined after phospholipase C hydrolysis, derivatization to dinitrobenzoates, and separation by high-performance liquid chromatography. In most molecular species, acyl groups at the sn-1 and sn-2 positions became 18O-labeled at drastically different rates, indicating remodeling through deacylation-reacylation. Molecular species expected to arise de novo from acylation of glycerophosphate exhibited similar rates of 18O incorporation at the sn-1 and sn-2 positions. The data suggest that hepatocyte phospholipids are continually synthesized, remodeled by deacylation reacylation at specific turnover rates up to 10-15%/h, and degraded. This acyl turnover probably does not involve the majority of intracellular unesterified fatty acids whose 18O incorporation was found to be very low. In contrast, the oxygens of extracellular unesterified fatty acids were readily exchanged with the media. This exchange was enzyme-catalyzed, possibly by lipases released into the media from damaged cells. Incorporation of 18O into exogenously added fatty acids was also rapid and resulted in enhanced uptake of 18O-labeled fatty acids into cellular lipids, primarily triacylglycerols and phosphatidylcholine, without drastic change of the intracellular free fatty acid pool. PMID- 1856203 TI - Co-regulation of a gene homologous to early light-induced genes in higher plants and beta-carotene biosynthesis in the alga Dunaliella bardawil. AB - Dunaliella bardawil, a unicellular green alga that can be induced to accumulate massive amounts of beta-carotene, is particularly suitable for studies of carotenogenesis regulation and its links to developmental and adaptive processes in the chloroplast. A cDNA clone corresponding to a transcript accumulating coordinately with carotenogenesis induction was isolated by differential hybridization of a cDNA library made from intensely illuminated cells. This transcript was also abundant in algal mutants able to accumulate beta-carotene under relatively low light intensity. DNA sequence analysis indicates that cbr (for carotene biosynthesis-related) is closely related to early light-induced genes (elip) of higher plants. Similarity also exists between repeated oligopeptide motifs in Cbr and Cab proteins of photosystems I and II. Three upstream direct repeats in cbr include an octamer and hexamer related to mammalian sterol regulatory elements. The relationship between cbr transcript and beta-carotene accumulation, the structural similarity between Cbr and Cab proteins, and the presence of potential SRE-1 elements lead us to propose that Cbr represents novel carotenoid binding proteins, whose synthesis might be coordinated with carotenogenic enzymes via an evolutionary conserved regulatory mechanism. PMID- 1856204 TI - Structure of the gene encoding human casein kinase II subunit beta. AB - Casein kinase II (CKII) is a ubiquitous serine/threonine protein kinase with numerous key functions in cell metabolism and growth. The human CKII has a tetrameric structure; two catalytic subunits (alpha and alpha') form the holoenzyme together with two presumably regulatory subunits (beta). The gene encoding CKII subunit beta was isolated from human genomic DNA and analyzed for its primary structure using exclusively nonradioactive procedures. The gene was found to span 4.2 kilobase pairs and to be composed of seven exons. Exon sizes range from 76 (exon 5) to 329 base pairs (bp) (exon 1), intron sizes from 145 (intron V) to 965 bp (intron II). All exon-intron junctional sequences conform to the canonical GT-AG rule. Primer extension analysis determined three transcription initiation sites, at 951, 919, and (minor) 840 bp upstream of the translation start site. The translation start is located early in the second exon; exon 1 is untranslated. The 3'-cleavage/polyadenylation signal sequence (AA TAAA) is in the last exon at position 4173 bp relative to the first transcription initiation site. The coding sequence for CKII beta comprises 648 nucleotides identical to the published CKII beta-cDNA sequence (Jakobi, R., Voss, H., and Pyerin, W. (1989) Eur. J. Biochem. 183, 227-233). The upstream promoter region of the CKII beta gene contains multiple potential gene regulatory sequence elements, noticeable DNA structures, and the characteristics of a housekeeping gene (more than one transcription initiation site, lack of a TATA-box, presence of a CpG island, occurrence of multiple GC boxes and of nonstandard positioned CCAAT boxes). The CKII beta gene promoter shares common features with that of mammalian protein kinases and is closely related to the regulatory subunit gene promoter of cAMP-dependent protein kinase. PMID- 1856205 TI - Identification, sequence, and expression of the gene encoding a Mr 35,000 subunit of the vaccinia virus DNA-dependent RNA polymerase. AB - The gene rpo35, encoding a subunit of the vaccinia virus DNA-dependent RNA polymerase, was identified, and its RNA and protein products were characterized. An Mr 35,000 polypeptide, which bound antibody to the purified RNA polymerase, was synthesized in reticulocyte lysates programmed with viral mRNA that hybridized to a 2,300-base pair segment of the viral genome. Determination of the sequence of the DNA segment revealed four potential protein coding regions, none of which had evident similarity to any described RNA polymerase subunit of prokaryotes or eukaryotes. One open reading frame that could encode a 35,400-Da protein was identified as rpo35 on the basis of mRNA hybridization, cell-free translation, and immunoprecipitation. The identification was confirmed by sequencing tryptic peptides of the authentic Mr 35,000 RNA polymerase subunit. Antiserum to the purified recombinant protein, expressed in bacteria, reacted specifically with a Mr 35,000 polypeptide that was detected starting 2 h after virus infection and that co-sedimented with RNA polymerase purified from virions. RNA analyses indicated that the 5'-end of an early transcript started 25 nucleotides upstream of rpo35, which is consistent with the location of an early promoter consensus sequence. PMID- 1856206 TI - Design of constructs for the expression of biologically active recombinant human factors X and Xa. Kinetic analysis of the expressed proteins. AB - Activation of vitamin K-dependent plasma proteases occurs by specific interaction with components of the blood coagulation cascade. In this report, we describe the direct expression and enzymatic characterization of the human coagulation zymogen factor X and its activated form, factor Xa, from transformed Chinese hamster ovary fibroblast cell lines. Expression was achieved using either a full-length factor X cDNA or a unique mutant factor Xa cDNA. The functional factor Xa precursor contained a novel tripeptide bridge in place of the native 52-amino acid activation peptide. This mutation allowed for intracellular processing and secretion of the activated form of factor X. Secreted recombinant factors X (rX) and Xa (rXa) were purified by sequential anion-exchange and immunoaffinity chromatography. The enzymatic activities of factors rX and rXa were compared with those of plasma factors X and Xa in three independent assay systems. In comparison to human plasma factor X, the amidolytic, prothrombinase complex, and plasma clotting activities of factor rX were 50, 85, and 43%, respectively. The corresponding comparative activities for factor rXa were 32, 64, and 48%, respectively. The ability to directly express mutant forms of biologically active human factor X will facilitate the structure/function analysis of this important blood coagulation protein and may lead to the development of novel coagulation inhibitors. PMID- 1856207 TI - Biosynthesis of islet amyloid polypeptide. Elevated expression in mouse beta TC3 cells. AB - Islet amyloid polypeptide (IAPP) messenger RNA levels, biosynthesis, processing, and secretion were studied in cultured mouse beta TC3 insulinoma cells. Northern blot analysis revealed that the size of IAPP mRNA (0.9 kb) in beta TC3 cells was the same as that in normal mouse islets; IAPP mRNA was approximately 60% of the level of insulin mRNA in beta TC3 cells. However, the ratio of synthesis of insulin to IAPP was approximately 6:1, suggesting that IAPP mRNA is not translated efficiently in these cells. Metabolic labeling of beta TC3 cells with [3H]leucine revealed the synthesis of both a precursor form of IAPP (pro-IAPP) of apparent Mr 7400 and a mature form (IAPP) of apparent Mr 3900. In pulse-chase experiments, pro-IAPP could be shown to be processed to IAPP in a manner similar to proinsulin. The t1/2 for conversion of pro-IAPP to IAPP was about 25 min, faster than the t1/2 for proinsulin to insulin of 70 min. A significant proportion of newly synthesized IAPP and insulin precursors were secreted via a constitutive pathway from beta TC3 cells. Possible effects of dexamethasone and forskolin on IAPP mRNA levels and biosynthesis were examined but no effects were observed. In conclusion, the IAPP gene is strongly expressed in beta TC3 cells leading to the biosynthesis, proteolytic processing, and secretion of IAPP, a putative islet hormone. PMID- 1856208 TI - Cross-linking of residue 57 in the regulatory domain of a mutant rabbit skeletal muscle troponin C to the inhibitory region of troponin I. AB - Interactions between troponin C (TnC) and troponin I (TnI) play an important role in the Ca(2+)-dependent regulation of vertebrate striated muscle contraction. In the present study, we investigated the sites of interaction between the N terminal regulatory domain of TnC and the inhibitory region (residues 96-116) of TnI, using a mutant rabbit skeletal TnC (designated as TnC57) that contains a single Cys at residue 57 in the C-helix. TnC57 was modified with the photoreactive cross-linker 4-maleimidobenzophenone (BP-Mal), and, after formation of a binary complex with TnI, cross-linking between the proteins was induced by photolysis. The resulting product was cleaved with CNBr and several proteases, and peptides containing cross-links were purified and subjected to amino acid sequencing. The results show that Cys-57 of TnC57 is cross-linked to the segment of TnI spanning residues 113-121. Previously, we showed that Cys-98 of TnC can be cross-linked via BP-Mal to TnI residues 103-110 (Leszyk, J., Collins, J.H., Leavis, P.C., and Tao, T. (1987) Biochemistry 26, 7042-7047). Taken together, these results demonstrate that both the C- and the N-terminal domains of TnC interact with the inhibitory region of TnI and are consistent with the hypothesis that, in a complex with TnI, TnC adopts a more compact conformation than in the crystal structure. PMID- 1856209 TI - Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor kB and CCAAT/enhancer-binding protein-like cis-elements. AB - Interleukin-8 (IL-8) is a newly described leukocyte chemotactic and activating cytokine that belongs to the novel family of inflammatory cytokines whose genes locate on human chromosome 4, q12-21 region. The production of IL-8 is usually not constitutive and can be induced rapidly and abundantly in different cell types by a variety of stimuli such as lipopolysaccharide, interleukin-1, tumor necrosis factor-alpha as well as a tumor promotor phorbol myristate acetate. We report here that in addition to these stimuli the IL-8 gene can also be induced by the protein X of the hepatitis B virus (HBV-X) as evidenced by the enhanced IL 8 mRNA expression and IL-8 production observed in HBV-X-transfected cells. Furthermore, using several deletion mutants of the 5'-flanking regulatory region of the human IL-8 gene linked to the chloramphenicol acetyl transferase gene as a reporter, we have established here that both nuclear factor kB and CCAAT/enhancer binding protein-like cis-elements located at -94 to -71 base pairs of IL-8 gene are essential and sufficient for the induction of the IL-8 gene by HBV-X. The same elements have been identified recently by us to be interleukin-1-, tumor necrosis factor-alpha-, and phorbol myristate acetate-responsive elements on the IL-8 gene. This suggests the existence of a common pathway for these inflammatory cytokines and HBV-X to activate the IL-8 gene. These observations might be relevant to the pathogenesis of inflammation in viral hepatitis. PMID- 1856210 TI - The polymeric hemoglobin molecule of Artemia. Interpretation of translated cDNA sequence of nine domains. AB - Translated cDNA for Artemia hemoglobin provided sequence data for almost nine domains, from the fourth residue of the A helix of one domain through 1405 residues to a stop codon after the ninth domain. The domain sequences were all different (homology between pairs 17-38%) but aligned well with each other and with conventional globins, satisfying the requirements for Phe at CD1, His at F8 and most other highly conserved features of globins including His at E7. Features found to be characteristic of Artemia globin and present in all nine domains were Phe at B10, Tyr at C4, Gly at F5, Phe at G5 and Gly at H22. Approximately 14 residues including a consensus -Val-Asp-Pro-Val-Thr-Gly-Leu- were available to form the linker between each pair of domains. The Artemia sequence data were compared with the crystal structures of Chironomus thummi thummi erythrocruorin III and sperm whale myoglobin in order to identify features of structural similarity and to examine the consequences of the differences. The Artemia sequences were compatible with the main helices and critical features of the globin fold. Possible modifications to the C helix, FG turn, and GH turn were studied in terms of molecular coordinates. PMID- 1856211 TI - Thrombin Glu-39 restricts the P'3 specificity to nonacidic residues. AB - Residue 39 of serine proteases neighbors positions P'2 to P'4 of the substrate. When Glu-39 of thrombin is replaced with Lys, the resultant enzyme (E39K) retains similar P1, P2, and P3 specificities but has altered P'3 and/or P'4 specificities. These conclusions are based on analysis of both p-nitroanilide and synthetic peptide hydrolysis. The activity of E39K is nearly normal toward 17 p nitroanilide substrates. In peptide substrates, an acidic residue at either the P3 or P'3 position reduces the rate of cleavage by thrombin. A single substitution of Asp with Gly in either the P3 or P'3 position of a peptide corresponding to the P7-P'5 residues of protein C increases the rate of cleavage by thrombin 2-3-fold. Replacement of both Asp residues with Gly increases the rate of cleavage 30-fold. With E39K, the inhibitory effect of Asp in P3 remains unchanged, but Asp in the P'3 site is no longer inhibitory. Significant differences in the catalytic activity of E39K are also seen with respect to protein C activation. In the absence of thrombomodulin, E39K activates protein C 2.2 times faster than thrombin. In the presence of thrombomodulin, the rate of protein C activation is similar for E39K and thrombin. The second order rate constant of inhibition by antithrombin III, where P'4 is a Glu, is slightly increased (1.4-fold). The clotting activity is reduced 2.4-fold due to a lower rate of fibrinopeptides A and B release where P'3 is Arg. These data show that the P'3 position is a determinant of thrombin specificity and suggest that thrombomodulin may function in part by alleviating the inhibitory effects that may arise from the proximity of the Asp in P'3 of protein C with Glu-39 of thrombin. PMID- 1856212 TI - Identification of critical amino acid residues in human and mouse granulocyte macrophage colony-stimulating factor and their involvement in species specificity. AB - Segments critical to the activity of human granulocyte-macrophage colony stimulating factor (GM-CSF) were identified by scanning deletion analysis and compared with the critical regions previously identified in the homologous mouse GM-CSF protein. Three of the four critical regions thus identified are in equivalent positions in their respective polypeptides, while a fourth critical region of each is uniquely located. To investigate whether unique critical regions are responsible for the observed species specificity of human and mouse GM-CSF, all critical regions were substituted into their opposite homologue. This identified one specific, but different, critical region in each homologue that could not be replaced. Further characterization of the nature of the species specificity of these two proteins was accomplished by the generation of a series of human/mouse GM-CSF hybrids. Each hybrid protein was assayed for specific activity on human- and mouse GM-CSF-dependent cell lines. Significant differences in the specific activity of these hybrids was observed, suggesting that different segments of each molecule interact with their respective receptors. Based on these two approaches, individual amino acids were identified that could provide, at least in part, the interactions between these protein ligands and their respective receptors. These residues are Thr-78 and Met-80 in human GM-CSF and Asp-92, Thr-98, and Asp-102 in mouse GM-CSF. PMID- 1856213 TI - Secretion in yeast. Purification and in vitro translocation of chemical amounts of prepro-alpha-factor. AB - The Saccharomyces cerevisiae mating pheromone precursor, prepro-alpha-factor, can be translocated across yeast endoplasmic reticulum membranes post-translationally in an in vitro system. This characteristic makes prepro-alpha-factor potentially useful as a probe in the biochemical dissection of the mechanism of this basic cellular process. Efforts have been limited by the inability to isolate sufficient quantities of such secretory protein precursors in a translocation competent form. We report here the one-step purification of chemical amounts of translocation-competent prepro-alpha-factor using nickel ion affinity chromatography on nitrilotriacetate resin. An oligonucleotide encoding 6 histidine residues was inserted into a genomic clone encoding prepro-alpha-factor 5' of the naturally occurring translational stop codon by site-directed mutagenesis. The construct was expressed at high levels in a SecY- strain of Escherichia coli. The produced preprotein was solubilized in 6 M guanidine hydrochloride and bound to nitrilotriacetate resin. Prepro-alpha-factor was recovered at a purity in excess of 95% by elution with 0.25 M imidazole, 8 M urea, which competitively displaced the histidine affinity tag from the nickel column. The chemical amounts of prepro-alpha-factor obtained in this way were determined to be competent for translocation across yeast microsomal membranes and for subsequent modifications such as signal sequence cleavage and N-linked glycosylation. PMID- 1856214 TI - Ribosomal proteins P0, P1, and P2 are phosphorylated by casein kinase II at their conserved carboxyl termini. AB - A potential casein kinase II (CK II) recognition site is located within the conserved carboxyl (COOH) terminus of the ribosomal P (phospho) proteins P0, P1, and P2. To determine whether the COOH termini of the P proteins are physiological substrates for CK II, we studied the phosphorylation of the P proteins in vitro and in intact cells. The results show that the addition of exogenous purified CK II and ATP to intact ribosomes in vitro resulted in the relatively selective phosphorylation of all three P proteins. A synthetic peptide corresponding to the COOH-terminal 22 amino acids of P2 (C-22) was also phosphorylated by CK II with a Km of 13.4 microM. An endogenous ribosome-associated, CK II-like enzyme also phosphorylated the P proteins relatively selectively in the presence of 10 mM Mg2+ and ATP. The endogenous kinase was inhibited by heparin, utilized either ATP or GTP as a phosphate donor, and phosphorylated casein. A CK II-specific peptide (Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu) and the C-22 peptide inhibited the phosphorylation of the P proteins by the endogenous kinase, providing further evidence for its CK II-like properties and for localization of the CK II phosphorylation site to the COOH termini of the P proteins. Tryptic phosphopeptide maps of P1 and P2 phosphorylated by exogenous CK II and the endogenous ribosome-bound kinase were virtually identical. These phosphopeptides comigrated with the tryptic digest of C-22 and with the tryptic phosphopeptides derived from P1 and P2 isolated from intact cells metabolically labeled with [32P]orthophosphate in vivo. These studies demonstrate that exogenous CK II and a ribosome-bound, CK II-like enzyme phosphorylate the ribosomal P proteins in vitro and localize the target site for phosphorylation to the COOH terminus. The incorporation of phosphate into the same target site in intact cells indicates that the P proteins are in vivo substrates of CK II. PMID- 1856215 TI - The chicken tropomyosin 1 gene generates nine mRNAs by alternative splicing. AB - Skeletal muscle beta-tropomyosin, smooth muscle alpha-tropomyosin, and a low molecular weight fibroblast tropomyosin are generated by alternatively splicing RNA transcripts of the chicken tropomyosin 1 (TM 1) gene (Forry-Schaudies, S., Maihle, N. J., and Hughes, S. H. (1990) J. Mol. Biol. 211; 321-330). Two novel tropomyosin cDNAs that derive from mRNAs of the TM 1 gene have been isolated from a chicken embryo brain cDNA library. Brain cDNA BRT-1 is 2.2 kilobases in length and encodes 283 amino acids. It is identical to skeletal muscle beta-tropomyosin from amino acids 1 to 258. The sequence 3' of this point is unique to BRT-1; a comparison to genomic sequence indicates that a new carboxyl-terminal exon is used to generate this sequence. 1.4-kilobase brain cDNA BRT-2 contains sequences found in both fibroblast cDNA FT-beta (5'-end) and skeletal muscle cDNA SKT-beta (3'-end). RNase and S1 nuclease assays using RNA samples from leg muscle, gizzard, fibroblasts, and brain indicate that the TM 1 gene expresses four additional tropomyosin RNAs by alternately splicing previously characterized exons. These results demonstrate that the chicken TM 1 gene encodes nine tropomyosin RNAs through the use of two promoters, two internal exons that are mutually exclusive, and three 3'-exons. Implications for the regulation of alternative splicing are discussed. PMID- 1856216 TI - Epidermal growth factor (EGF) induces oligomerization of soluble, extracellular, ligand-binding domain of EGF receptor. A low resolution projection structure of the ligand-binding domain. AB - Ligand-induced oligomerization is a universal phenomenon among growth factor receptors. Although the mechanism involved is yet to be defined, much evidence indicates that receptor oligomerization plays a crucial role in receptor activation and signal transduction. Here we show that epidermal growth factor (EGF) is able to stimulate the oligomerization of a recombinant, soluble, extracellular ligand-binding domain of EGF receptor. Covalent cross-linking experiments, analysis by sodium dodecyl sulfate-gel electrophoresis, size exclusion chromatography, and electron microscopy demonstrate that receptor dimers, trimers and larger multimers are formed in response to EGF. This establishes that receptor oligomerization is an intrinsic property of the extracellular ligand-binding domain of EGF receptor. Ligand-induced conformational change in the extracellular domain will stimulate receptor receptor interactions. This may bring about the allosteric change involved in signal transduction from the extracellular domain across the plasma membrane, resulting in the activation of the cytoplasmic kinase domain. Electron microscopic images of individual extracellular ligand-binding domains appear as clusters of four similarly-sized stain-excluding areas arranged around a central, relatively less stain-excluded area. This suggests that the extracellular ligand binding domain is structurally composed of four separate domains. PMID- 1856217 TI - Outer membrane translocation of the extracellular enzyme pullulanase in Escherichia coli K12 does not require a fatty acylated N-terminal cysteine. AB - Site-directed mutagenesis was used to construct three mutant derivatives of the extracellular, cell surface lipoprotein pullulanase (PulA) in which the normally fatty acylated cysteine of the signal peptide-bearing precursor was replaced by other amino acids. When produced in Escherichia coli expressing all genes required for pullulanase secretion, approximately 90% of the PulA derivatives persisted as cell-associated precursors, indicating inefficient signal peptide processing. Processed (intermediate-sized) forms of the two derivatives that were studied in detail were found to result from proteolytic cleavage at different sites within the signal peptide. Both were further processed to smaller polypeptides by cleavage at an undetermined site that is presumably close to their C termini. The intermediate-sized pullulanase derived from prepullulanase in which Cys+1 had been replaced by Leu and Gly-1 by Glu (PulA:C1L/G-1E) appeared rapidly, was apparently entirely extracellular, and accounted for approximately 10% of synthesized PulA. Prolonged incubation did not result in further conversion of the precursor to the intermediate form, and the precursor remained anchored to the cytoplasmic membrane. The smaller processed form was also found extracellularly. The active form of the extracellular enzyme was monomeric, which is again in contrast to the fatty acylated, wild-type enzyme. Taken together, these results indicate that replacement of Cys+1 of prePulA eliminates processing by lipoprotein signal peptidase and does not permit processing by leader peptidase, but allows inefficient, aberrant processing by an unknown peptidase and immediate secretion of the resulting polypeptide, which retains most of its signal peptide. Processing and secretion only occur when the pullulanase secretion functions are expressed. PMID- 1856218 TI - Ethidium bromide does not fluoresce when intercalated adjacent to 7-deazaguanine in duplex DNA. AB - Several synthetic DNAs were prepared containing the unusual bases 7-deazaadenine (c7A) and 7-deazaguanine (c7G). As judged from changes in melting temperatures these modified DNAs bound ethidium to a similar extent as the parent polymers. However, duplexes such as poly [d(Tc7G)].poly[d(CA)] and poly[d (TC)].poly[d(c7GA]) gave no enhancement of ethidium fluorescence in a standard ethidium fluorescence assay. Fluorescence spectra in the range 400-650 nm showed that ethidium bound to poly[d(TC)].poly[d(Gc7A)] gave 70% of the fluorescence of the parent polymer poly[d(TC)].poly[d(GA)], whereas the fluorescence of poly[d(TC)].poly[d(c7GA)] was essentially 0%. Even the intrinsic fluorescence of ethidium in solution was quenched in the presence of poly[d(TC)].poly[d(c7GA)]. Binding constants were estimated from Scatchard analysis and were 4.8, 3.4, and 2.0 x 10(6) M-1 for poly[d(TC)].poly[d(GA)], poly[d(TC)].poly[d(Gc7A)], and poly[d(TC)].poly[d(c7GA)], respectively. This reduction in binding constant cannot account for the loss of fluorescence. The UV spectrum of ethidium was measured in the presence of these DNAs, and some significant differences were noted. Presumably the presence of 7-deazaguanine alters the electronic structure of bound ethidium so that it can no longer fluoresce. PMID- 1856219 TI - The oxidative inactivation of plasminogen activator inhibitor type 1 results from a conformational change in the molecule and does not require the involvement of the P1' methionine. AB - Plasminogen activator inhibitor 1 (PAI-1) is sensitive to oxidative inactivation, and it has been suggested that specific oxidation of a methionine residue, Met347, situated in the P1' position of the reactive center may be the cause of the inactivation. To test this hypothesis we have purified and biochemically characterized mutant proteins of PAI-1 in which Met347 and either of two other methionines, Met266 or Met354, has been replaced with oxidation-resistant valine residues. The mutant proteins were found to be equally sensitive to oxidation as wild-type PAI-1, suggesting that a specific oxidation of the P1' Met347 is not responsible for the inactivation. When PAI-1 was oxidized, circular dichroism analysis revealed a rapid conformational change that correlated to the loss of inhibitory activity. The oxidation sensitivity of PAI-1 was enhanced dramatically in the presence of 0.001% sodium dodecyl sulfate, and the circular dichroism spectrum was significantly different from that of untreated PAI-1, suggesting that the increased sensitivity to oxidation may be caused by a conformational change in the inhibitor molecule. Taken together, our data suggest that the oxidative inactivation of PAI-1 is not caused by the specific oxidation of the P1' methionine but results from a conformational change in the protein structure. PMID- 1856220 TI - Myristic acid utilization and processing in BC3H1 muscle cells. AB - Because myristic acid (14:0) is important in regulating cell function, we have studied its utilization in BC3H1 muscle cells. Phosphatidylcholine contained 70 80% of the [9,10-3H]14:0 radioactivity incorporated into the cell phospholipids. In both myoblasts and myocytes, however, large amounts of radioactivity also accumulated in a labile neutral lipid pool consisting mostly of triacylglycerol. Therefore, radioactive lipid products formed when BC3H1 cells labeled with 14:0 are stimulated are not necessarily derived only from phosphatidylcholine. Elongation of [9,10-3H]14:0 occurred rapidly in the myoblasts and myocytes, and extensive desaturation also occurred in the myoblasts. Thus, even after short periods of labeling, substantial amounts of radioactivity are contained in fatty acids other than 14:0. The labeling of proteins with [9,10-3H]myristic acid was generally similar in the myoblasts and myocytes. A number of lipid-soluble, polar radioactive metabolites were released into the medium during incubation of [9,10 3H]14:0 with the cells. [1-14C] 14:0 was not converted to these compounds, indicating that they are chain-shortened 14:0 derivatives. Based on chemical analysis, two of the major products appear to be hydroxylated fatty acids. This oxidation process shows some specificity for 14:0 because similar compounds were not produced from palmitic, oleic, or linoleic acids. The myocytes formed larger amounts of the metabolites than the myoblasts, suggesting that differentiation may increase the activity of this 14:0 oxidative pathway. PMID- 1856221 TI - Biosynthesis of glycosylated human lysozyme mutants. AB - Complementary DNA encoding human lysozyme was subjected to oligonucleotide directed mutagenesis. At one of three selected positions, amino acid residues 22, 68, or 118, the signal for N-linked glycosylation was created. The mutant DNAs were inserted into a eucaryotic vector and transfected into cultured hamster cells. The three mutant cDNAs directed synthesis of lysozyme mutants, which were named LI, LII, and LIII. The mutant lysozymes LI and LII comprised mixtures of glycosylated and nonglycosylated forms. The glycosylated and nonglycosylated forms of mutant LI were found to have an enzymatic activity similar to normal human milk lysozyme. The usage of the glycosylation sites in the mutants was similar in Chinese hamster ovary (CHO) and baby hamster kidney cells. Approximately two of every three molecules in mutant LI, approximately one of every eight molecules in mutant LII, and practically no molecules in mutant LIII became glycosylated. In CHO cells, the processing of the oligosaccharide side chains yielded several larger products than in baby hamster kidney cells. This size variability of glycosylated lysozyme from CHO cells may be explained by the presence of biantennary and triantennary endo-beta-N-acetylglucosaminidase H resistant oligosaccharides with N-acetyllactosamine repeats of variable length and by the presence of hybrid oligosaccharides, as suggested by affinity to several lectins and sensitivity to endo-beta-galactosidase. In both cell types, the majority of the glycosylated forms were secreted and thus behaved similarly to nonglycosylated lysozyme. A small proportion of mutant LI lysozyme remained associated with the cells. The retained lysozyme was recruited predominantly from the molecules bearing high mannose oligosaccharides. These molecules were targeted to lysosomes, and their carbohydrate was trimmed to an endo-beta-N acetylglucosaminidase H-resistant form. Owing to the small size of mutant LI lysozyme, minor changes in the size of its carbohydrate moiety result in detectable changes in the electrophoretic mobility of the whole glycoprotein. We suggest that this novel glycoprotein could be used as a reporter in studies on processing and segregation of glycoproteins. PMID- 1856222 TI - Differential regulation of iron regulatory element-binding protein(s) in cell extracts of activated lymphocytes versus monocytes-macrophages. AB - The intracellular iron level exerts a negative feedback on transferrin receptor (TfR) expression in cells requiring iron for their proliferation, in contrast to the positive feedback observed in monocytes-macrophages. It has been suggested recently that modulation of TfR and ferritin synthesis by iron is mediated through a cytoplasmic protein(s) (iron regulatory element-binding protein(s) (IRE BP)), which interacts with ferritin and TfR mRNA at the level of hairpin structures (IRE), thus leading to inhibition of transferrin mRNA degradation and repression of ferritin mRNA translation. In the present study we have evaluated in parallel the level of TfR expression, ferritin, and IRE-BP in cultures of: (i) circulating human lymphocytes stimulated to proliferate by phytohemagglutinin (PHA) and (ii) circulating human monocytes maturing in vitro to macrophages. The cells were grown in either standard or iron-supplemented culture. TfR and ferritin expression was evaluated at both the protein and mRNA level. IRE-BP activity was measured by gel retardation assay in the absence or presence of beta mercaptoethanol (spontaneous or total IRE-BP activity, respectively). Spontaneous IRE-BP activity, already present at low level in quiescent T lymphocytes, shows a gradual and marked increase in PHA-stimulated T cells from day 1 of culture onward. This increase is directly and strictly correlated with the initiation and gradual rise of TfR expression, which is in turn associated with a decrease of ferritin content. Both the rise of TfR and spontaneous IRE-BP activity are completely inhibited in iron-supplemented T cell cultures. In contrast, the total IRE-BP level is similar in both quiescent and PHA-stimulated lymphocytes, grown in cultures supplemented or not with iron salts. Monocytes maturing in vitro to macrophages show a sharp increase of spontaneous and, to a lesser extent, total IRE-BP; the addition of iron moderately stimulates the spontaneous IRE-BP activity but not the total one. Here again, the rise of spontaneous IRE-BP from very low to high activity is strictly related to the parallel increase of TfR expression and, suprisingly, also with a very pronounced rise of ferritin expression observed at both the mRNA and protein level. It is noteworthy the effect of beta-mercaptoethanol is cell specific, i.e. the ratio of total versus spontaneous IRE-BP activity is different in activated lymphocytes and maturing monocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1856223 TI - Single nucleotide resolution of sterol regulatory region in promoter for 3 hydroxy-3-methylglutaryl coenzyme A reductase. AB - Sterol-dependent regulation of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase promoter was previously localized to a 42-base pair region containing an octamer sequence, referred to as the sterol regulatory element (SRE 1). A similar motif is found in the region of DNA that is required for sterol dependent regulation of the HMG-CoA synthase and low density lipoprotein receptor genes. Single nucleotide substitution analyses of the low density lipoprotein receptor and HMG-CoA synthase promoters confirmed that the SRE-1 is an important sterol regulatory motif. In the current studies, a series of single nucleotide mutations were introduced into the HMG-CoA reductase regulatory region and transfected into Chinese hamster ovary cells. RNA produced by each mutant promoter was then measured in the presence or absence of sterols. Thirty-seven independent mutations were analyzed, and two separate domains were identified as being critical. One essential region was spread over 10 bases and contained half of the SRE-1; however, the other half of the SRE-1 was not important for sterol regulation. The second essential region spanned four contiguous bases. These two critical elements are separated from each other by three nonessential bases. The results are interpreted to suggest that regulation of HMG-CoA reductase gene transcription by sterols requires additional or possibly separate factors from those required for sterol regulation of the low density lipoprotein receptor and HMG-CoA synthase promoters. PMID- 1856224 TI - The HgaI restriction-modification system contains two cytosine methylase genes responsible for modification of different DNA strands. AB - A DNA fragment of about 3.4 kilobase pairs that expressed the HgaI modification activity was cloned from the chromosomal DNA of Haemophilus gallinarum, and its nucleotide sequence was determined. Two open reading frames (ORF) which could code for structurally similar proteins were identified in the upstream and middle regions and a truncated ORF in the downstream region in the same orientation. When the respective ORFs were separately cloned, the clones carrying the upstream and middle ORFs both expressed the modification activity, indicating that the two genes are involved in modification of the HgaI restriction-modification system. In order to determine the sites of modification precisely, the respective genes were recloned into an expression vector, from which gene products were purified. A short DNA fragment carrying the HgaI recognition site was treated with each of these enzymes, and, after separation of the two strands by duplex formation with M13 viral DNAs carrying the respective strands, the presence or absence of modification was judged from susceptibility to HgaI endonuclease. The results of analysis showed that different strands were modified in an asymmetric way by each gene product. Analysis of the species and positions of modified bases by the Maxam-Gilbert method further demonstrated that the gene products from the upstream and middle ORFs participated in methylation of the internal cytosine residues of the strands carrying 3'-CTGCG-5' and 5'-GACGC-3', respectively. We concluded that the HgaI modification system consisted of two cytosine methylase genes responsible for modification of different strands in the target DNA. PMID- 1856226 TI - Localization and structure of the asparagine-linked oligosaccharides of type IV collagen from glomerular basement membrane and lens capsule. AB - Analysis of the Sephacryl S-200 fractionated type IV collagen domains from bovine and human glomerular basement membranes (GBM) and calf anterior lens capsule (ALC) indicated that Asn-linked oligosaccharides are primarily or exclusively localized in the 7 S region, whereas the hydroxylysine-linked Glc alpha 1----2Gal disaccharides (Glc-Gal-Hyl) are present in all the major segments of the molecule (7 S, NC1, and helical domain); no Ser/Thr-linked saccharide were detected. The Asn-linked carbohydrate units observed in the 7 S domain (Mr approximately 300,000) occurred in a number equal to the 12 polypeptide chains constituting this cross-linked region, and this was consistent with lectin blots of the reduced electrophoretically resolved 7 S components. Fractionation of the N glycanase and endo-beta-N-acetylglucosaminidase-released oligosaccharides by concanavalin A affinity and high performance liquid chromatography indicated that the Asn-linked carbohydrate occurred predominantly in the form of complex tri- and biantennary units, although submolar amounts of polymannose variants (Man5 7GlcNAc2) were also present in calf ALC and bovine GBM. Structural studies of the complex N-linked oligosaccharides employing hydrazine/nitrous acid fragmentation and glycosidase digestions indicated a pattern in which there was complete fucosylation of the innermost GlcNAc residue of the Man3GlcNAc2 core but only sparse substitution with capping groups of the nonrepeating N-acetyllactosamine branches. Whether tri- or biantennary, the oligosaccharides from bovine GBM contained only one capping residue, in the form of either NeuAc or alpha-D-Gal, whereas those from ALC had only a single alpha-D-Gal and no NeuAc; human GBM oligosaccharides were devoid of both NeuAc and alpha-D-Gal. The absence of terminal alpha-D-Gal in the human 7 S domain was reflected in its lack of reactivity with Bandeiraea simplicifolia I and from its failure to yield Gal alpha 1----3Gal beta 1----4 [3H]anhydromannitol after hydrazine/nitrous acid/NaB3H4 treatment. Application of the latter procedure to the collagen domains yielded, in addition to fragments from the N-linked oligosaccharides, a disaccharide (Glc alpha 1----2[3H]galactitol) derived from the Glc-Gal-Hyl units. The localization of Asn-linked carbohydrate units in the evolutionarily conserved 7S domain of type IV collagens suggests that these oligosaccharides may play a role in the assembly of the collagen network of basement membranes. PMID- 1856227 TI - The priB and priC replication proteins of Escherichia coli. Genes, DNA sequence, overexpression, and purification. AB - The Escherichia coli DNA replication proteins n and n" function in vitro in the assembly of the primosome, a mobile multiprotein replication priming complex thought to operate on the lagging-strand template at the E. coli DNA replication fork. Both proteins have been purified from E. coli HMS83 cells based on their requirement for the reconstitution of bacteriophage phi X174 complementary strand DNA synthesis in vitro with purified proteins. As a step toward understanding the role of these proteins in vivo, the genes for primosomal proteins n and n", designated priB and priC, respectively, have been cloned molecularly. priB encodes a 104-amino acid 11.4-kDa polypeptide and corresponds to an previously identified open reading frame between rpsF and rps R within a ribosomal protein operon at 95.5 min on the E. coli chromosome. priC encodes a 175-amino acid 20.3 kDa polypeptide. These two gene products were overexpressed at least 1000-fold in E. coli using a bacteriophage T7 transient expression system. Both proteins have been purified to apparent homogeneity from extracts prepared from these overproducing strains. PMID- 1856225 TI - A long helix from the central region of smooth muscle caldesmon. AB - The central region of smooth muscle caldesmon is predicted to form alpha-helices on the basis of its primary structure. We have isolated a fragment (CT54) that contains this region. The hydrodynamic properties and the electron microscopic images suggest that CT54 is an elongated (35 nm), monomeric molecule. The circular dichroic spectrum yields an overall alpha-helical content of 55-58%. These results are consistent with the model that the middle portion of CT54 forms a long stretch of single-stranded alpha-helix. Such a structure, if it in fact exists, is thought to be stabilized by numerous salt bridges between charged residues at positions i and i + 4. The structural characteristics of this fragment not only represent an unusual protein configuration but also provide information about the functional role of caldesmon in smooth muscle contraction. PMID- 1856228 TI - Immunoglobulins as nucleating proteins in the gallbladder bile of patients with cholesterol gallstones. AB - The gallbladder bile of patients with cholesterol gallstones contains pronucleating proteins which accelerate precipitation of cholesterol crystals from bile. In this study we have improved the purification procedure developed earlier for these nucleating proteins and have now identified the nature of these proteins. Gallbladder bile from patients with cholesterol gallstones was applied to concanavalin A affinity columns. The ConA-binding glycoprotein fractions containing the nucleating proteins were then separated by FPLC (fast protein liquid chromatography) using a Superose 12 gel filtration column. Nucleating activity was detected in the high molecular weight (FPLC-1) as well as in the low molecular weight fractions (FPLC-3). Investigation of the high molecular weight fraction by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by electroelution and amino acid sequencing suggested that these proteins were immunoglobulins. Immunostaining of Western blots with specific monoclonal antibodies identified the presence of immunoglobulin (Ig) M and IgA in the FPLC-1 fraction. These immunoglobulins were further purified by affinity chromatography employing an antibody exchanger (ABx) column which specifically binds immunoglobulins. There was no reduction in the cholesterol nucleating activity in the Abx-bound fraction compared to FPLC-1. Additional studies showed that the FPLC-1 fraction was significantly more potent than the ConA glycoproteins from either rapid and slow nucleating biles. Also the number of crystals formed was significantly greater in the FPLC-1 fraction isolated from cholesterol gallstone biles than from the FPLC-1 fraction from control patient biles. Commercially obtained IgM and IgA had no effect on nucleation, but IgM isolated from the serum of patients with Waldenstrom's macroglobulinemia did accelerate the nucleation of cholesterol. We conclude that the IgM and possibly IgA are pronucleating proteins and may be important in the pathogenesis of cholesterol gallstones in man. PMID- 1856229 TI - Bovine liver aspartyl beta-hydroxylase. Purification and characterization. AB - The alpha-ketoglutarate-dependent dioxygenase, L-asp(L-Asn)-beta-hydroxylase which posttranslationally hydroxylates specific aspartic acid (asparagine) residues within epidermal growth factor-like domains was purified from bovine liver and characterized. A 52-kDa and a 56-kDa species of this enzyme, which accounted for 60 and 30% of the total enzymatic activity, respectively, were purified to apparent homogeneity. Amino-terminal sequence analyses and immunoblots utilizing antisera raised to the intact 52-kDa species as well as to two complementary fragments of this species demonstrated that the 52- and 56-kDa species differ by a 22-amino acid amino-terminal extension. The remaining 10% of the purified enzymatic activity could be accounted for by the presence of immunologically related higher molecular mass forms (56-90 kDa) of L-Asp(L-Asn) beta-hydroxylase. Strong evidence was obtained from the results of immunoextraction studies that L-Asp(L-Asn)-beta-hydroxylase can be identified with the purified proteins. Kinetic and physical studies suggest that L-Asp(L Asn)-beta-hydroxylase exists as a monomer with a compact catalytic domain and an extended protease-sensitive amino terminus whose function remains to be determined. Since the purified L-Asp(L-Asn)-beta-hydroxylase hydroxylated both L Asp- and L-Asn-containing substrates, it is possible that a single enzyme is responsible for the hydroxylation of Asp and Asn residues in vivo. PMID- 1856230 TI - Function of eukaryotic initiation factor 5 in the formation of an 80 S ribosomal polypeptide chain initiation complex. AB - Eukaryotic initiation factor 5 (eIF-5), isolated from rabbit reticulocyte lysates, is a monomeric protein of 58-62 kDa. The function of eIF-5 in the formation of an 80 S polypeptide chain initiation complex from a 40 S initiation complex has been investigated. Incubation of the isolated 40 S initiation complex (40 S.AUG.Met.tRNAf.eIF-2 GTP) with eIF-5 resulted in the rapid and quantitative hydrolysis of GTP bound to the 40 S initiation complex. The rate of this reaction was unaffected by the presence of 60 S ribosomal subunits. Analysis of eIF-5 catalyzed reaction products by gel filtration indicated that both eIF-2.GDP binary complex and Pi formed were released from the ribosomal complex whereas Met tRNAf remained bound to 40 S ribosomes as a Met-tRNAf.40 S.AUG complex. Reactions carried out with biologically active 32P-labeled eIF-5 indicated that this protein was not associated with the 40 S.AUG.Met-tRNAf complex; similar results were obtained by immunological methods using monospecific anti-eIF-5 antibodies. The isolated 40 S.AUG.Met-RNAf complex, free of eIF-2.GDP binary complex and eIF 5, readily interacted with 60 S ribosomal subunits in the absence of exogenously added eIF-5 to form the 80 S initiation complex capable of transferring Met-tRNAf into peptide linkages. These results indicate that the sole function of eIF-5 in the initiation of protein synthesis is to mediate hydrolysis of GTP bound to the 40 S initiation complex in the absence of 60 S ribosomal subunits. This leads to formation of the intermediate 40 S.AUG.Met-tRNAf and dissociation of the eIF 2.GDP binary complex. Subsequent joining of 60 S ribosomal subunits to the intermediate 40 S.AUG.Met-tRNAf complex does not require participation of eIF-5. Thus, the formation of an 80 S ribosomal polypeptide chain initiation complex from a 40 S ribosomal initiation complex can be summarized by the following sequence of partial reactions. (40 S.AUG.Met-tRNAf.eIF-2.GTP) eIF-5----(40 S.AUG.Met-tRNAf) + (eIF-2.GDP) + Pi (1) (40 S.AUG.Met-tRNAf) + 60 S----(80 S.AUG.Met-tRNAf) (2) 80 S initiation complex. PMID- 1856231 TI - Strand exchange protein 1 from Saccharomyces cerevisiae. A novel multifunctional protein that contains DNA strand exchange and exonuclease activities. AB - Strand exchange protein 1 (Sep1) from Saccharomyces cerevisiae catalyzes the formation of heteroduplex DNA molecules from single-stranded circles and homologous linear duplex DNA in vitro. Previously, Sep1 was purified as a 132,000 Da species; however, DNA sequence analysis indicates that the SEP1 gene is capable of encoding a 175,000-Da protein (Tishkoff, D.X., Johnson, A.W., and Kolodner, R.D. (1991) Mol. Cell. Biol. 11, 2593-2608). The SEP1 gene was cloned into a GAL10 expression vector and expressed in a protease-deficient yeast strain. Intact Sep1, which migrated as a Mr-160,000 polypeptide during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was purified to apparent homogeneity and shown to have activities similar to those of the originally purified Mr = 132,000 fragment. We report here that, in addition to strand exchange activity, Sep1 contains an intrinsic exonuclease that is active on single- and double-stranded DNA with a severalfold preference for single-stranded DNA. The nuclease was induced in crude extracts upon induction with galactose, it co-purified with the strand exchange activity of Sep1, and the nuclease and strand exchange activities of Sep1 showed the same kinetics of heat inactivation. Sep1 nuclease, which requires Mg2+, can be functionally separated from the strand exchange activity by the substitution of Ca2+ for Mg2+. Under these conditions, the nuclease is inactive, and strand exchange activity is dependent on prior resection of the DNA ends by an exogenous exonuclease. Thus, the nuclease is necessary for synapsis but not strand exchange. Electron microscopic analysis revealed that true strand exchange products, alpha molecules and nicked double stranded circular molecules, were formed. In addition, strand transfer proceeded to similar extents on 5'-resected and 3'-resected DNA. This result suggests that the polarity of strand transfer by Sep1 is determined by the polarity of its intrinsic nuclease. PMID- 1856232 TI - Properties of the collagenous domain of the alpha 3(IV) chain, the Goodpasture antigen, of lens basement membrane collagen. Selective cleavage of alpha (IV) chains with retention of their triple helical structure and noncollagenous domain. AB - A third chain, alpha 3(IV), of basement membrane collagen was recently discovered and was identified as the primary target for the autoantibodies of patients with Goodpasture syndrome (Saus, J., Wieslander, J., Langeveld, J. P. M., Quinones, S., and Hudson, B. G. (1988) J. Biol. Chem. 263, 13374-13380). In the present study, this chain was excised in the form of a truncated promoter by cleavage of basement membrane with Pseudomonas aeruginosa elastase and characterized. The triple helical structure and NC1 domain were retained. Elastase selectively cleaved at a site within the triple helical domain of the alpha 3 chain that is distinct from the cleavage site of the alpha 1 and alpha 2 chains. The truncated alpha 3 chain was found to contain 1460 residues, of which 1225 comprise the collagenous domain, and is cross-linked within this domain by disulfide bonds, forming a high Mr complex (greater than 300,000). Truncated protomers with a length of 340 nm corresponding to the theoretical length for the truncated alpha 3 chain were observed by electron microscopy as suprastructures in which the triple helical domains of three protomers were interwined. These protomers were also connected to each other and to the 140-nm protomers that appear to be comprised of the alpha 1 and alpha 2 chains. These results extended the known length of the alpha 3 chain by about 1000 residues and suggested that protomers of this chain self-associate through interactions between their triple helical domains and between their NC1 domains. PMID- 1856233 TI - Single-chain site-specific mutations of fluorescein-amino acid contact residues in high affinity monoclonal antibody 4-4-20. AB - Previous crystallographic studies of high affinity anti-fluorescein monoclonal antibody 4-4-20 (Ka = 1.7 x 10(10) M-1) complexed with fluorescyl ligand resolved active site contact residues involved in binding. For better definition of the relative roles of three light chain antigen contact residues (L27dhis, L32tyr and L34arg), four site-specific mutations (L27dhis to L27lys, L32tyr to L32phe, and L34arg to L34lys and L34his) were generated and expressed in single-chain antigen binding derivatives of monoclonal antibody 4-4-20 containing two different polypeptide linkers (SCA 4-4-20/205c, 25 amino acids and SCA 4-4-20/212, 14 amino acids). Results showed that L27dhis and L32tyr were necessary for wild type binding affinities, however, were not required for near-wild type Qmax values (where Qmax is the maximum fluoroscein fluorescence quenching expressed as percent). Tyrosine L32 which hydrogen bonds with ligand was also characterized at the haptenic level through the use of 9-hydroxyphenylfluoron which lacks the carboxyl group to which L32 tyrosine forms a hydrogen bond. Results demonstrated that wild type SCA and mutant L32phe possessed similar HPF binding characteristics. Active site contact residue L34arg was important for fluorescein quenching maxima and binding affinity (L34his mutant), however, substitution of lysine for arginine at L34 did not have a significant effect on observed Qmax value. In addition, substitutions had no effect on structural and topological characteristics, since all mutants retained similar idiotypic and metatypic properties. Finally, two linkers were comparatively examined to determine relative contributions to mutant binding properties and stability. No linker effects were observed. Collectively, these results verified the importance of these light chain fluorescein contact residues in the binding pocket of monoclonal antibody 4-4-20. PMID- 1856234 TI - Expression of lysosomal cathepsin B during calf myoblast-myotube differentiation. Characterization of a cDNA encoding bovine cathepsin B. AB - Expression of lysosomal cysteine proteinases was studied during fetal calf myoblast-myotube differentiation. Activities of cathepsin B and L, but not cathepsin H, increase during bovine myogenic differentiation. In fetal muscle, cathepsin B and L activities are 2-4-fold orders of magnitude lower than in cultured myoblasts. Active-site titrations of cathepsin B with E-64 nevertheless reveal similar concentrations of active cathepsin B in myoblasts and myotubes, but 5-6-fold lower concentrations in fetal muscle. To specify whether concentrations of cathepsin B are related to levels of cathepsin B transcript, a cDNA clone encoding bovine cathepsin B was isolated and liquid hybridizations were performed with 32P-riboprobes complementary to the mRNA. In agreement with active-site titrations, there is no difference in cathepsin B mRNA levels between cultured myoblasts and myotubes, but lower levels of mRNA are found in fetal muscle. Concentrations of active cathepsin B therefore reflect levels of cathepsin B mRNA. Kinetic studies revealed that the catalytic efficiency (kcat/Km) of cathepsin B is 2-3-fold higher in myotubes than in myoblasts. The increase in cathepsin B activity during calf myoblast-myotube differentiation is thus due to modifications of enzymatic properties, and not of enzyme concentrations. The different catalytic efficiency of cathepsin B in myotubes and myoblasts was related neither to modifications of mRNA size, as revealed by Northern blot analysis, nor to a different Mr of the active enzyme, as revealed by affinity labeling with benzyloxycarbonyl-Tyr(-125I)-Ala-CHN2, but to limited differences in cathepsin B isozymes. PMID- 1856236 TI - A retinoic acid-inducible mRNA from F9 teratocarcinoma cells encodes a novel protease inhibitor homolog. PMID- 1856235 TI - Maltose transacetylase of Escherichia coli. Mapping and cloning of its structural, gene, mac, and characterization of the enzyme as a dimer of identical polypeptides with a molecular weight of 20,000. AB - malQ mutants, lacking amylomaltase, cannot grown on maltose. However, when maltose is present in the medium, it can be accumulated to high internal levels. In a subsequent slow reaction, accumulated maltose becomes acetylated and leaks back into the medium. The enzyme responsible for this acetylation uses acetyl-CoA as acetyl donor and can be measured in crude extracts (Boos, W., Ferenci, T., and Shuman, H. A. (1981) J. Bacteriol. 146, 725-732). The structural gene for the enzyme, which we named mac, was mapped at 10.4 min on the Escherichia coli linkage map. We cloned a 3.4-kilobase pair PstI-EcoRI DNA fragment containing the mac gene. Cell-free extracts of a strain harboring the multicopy plasmid were used to purify the maltose-transacetylating activity to apparent homogeneity. On sodium dodecyl sulfate-polyacrylamide gels the enzyme exhibited a molecular weight of 20,000. Using molecular sieve chromatography, a molecular weight of 40,000 was determined for the native enzyme. Therefore, the enzyme is a dimer of two identical subunits. At a sugar concentration of 100 mM the enzyme acetylates glucose, maltose, mannose, galactose, and fructose in decreasing relative rate of 1, 0.55, 0.20, 0.07, 0.04. Maltotriose and other oligosaccharides were acetylated with 2% of the rate determined for glucose. The Km for glucose and maltose were 62 and 90 mM, and the Vmax was 0.20 and 0.11 mmol/min x mg enzyme, respectively. PMID- 1856237 TI - Apparatus to obtain rotational flexibility of the human knee under moment loads in vivo. AB - The contributions of this paper are twofold. One is the design and performance evaluation of new equipment to determine the rotational flexibility of the human knee in vivo. Since determining knee flexibility requires the application of external loads and the measurement of knee rotations, the new equipment consists of a load application stand and a triaxial goniometer. The triaxial goniometer noninvasively mounts to the leg and directly measures the relative three degrees of-freedom rotations of the knee sequentially and independently. The goniometer incorporates several unique design features which enhance measurement accuracy. The load stand applies pure varus/valgus and external/internal axial moments either individually or in combination through the use of motors controlled by the test subject. Unique to this design are features which enable the application of moments to the knee which minimise shear forces. Other unique design features permit the stand to control hip and knee flexion angles, muscle contraction, and axial loading. To assess the accuracy with which rotations are measured during experiments, three tests were conducted with the equipment. One test evaluated the inherent accuracy of the goniometer, a second test assessed the potential for goniometer slippage during loading, and a third explored the effect of goniometer mounting on the repeatability of results. A special verification apparatus facilitated evaluation of goniometer inherent accuracy. A second contribution of the paper is an investigation of the effect of foot constraints (i.e. boundary conditions) on flexibility results. To make this investigation, three subjects were tested with the knee at 15 degrees of flexion. Results revealed large differences in flexibility between constraining the foot in both external/internal and varus/valgus rotations and permitting the foot to rotate freely in the direction not being loaded. Further, constraint moments as high as 23 Nm were also recorded. These results emphasise that in order to obtain accurate flexibility results for isolated loads, the foot must be unconstrained by the loading apparatus. PMID- 1856238 TI - Development of a three-dimensional finite element model of a human tibia using experimental modal analysis. AB - The modal analysis of a human tibia consisted of characterizing its dynamic behavior by determining natural frequency, damping ratio and mode shapes. Two methods were used to perform the modal analysis: (1) a finite element method (structural model); (2) an experimental modal analysis (modal model). The experimental modal model was used to optimize the structural model. After optimization, differences in results between the two models were found to be due only to mechanical properties and mass distribution. The influences of boundary conditions and geometric properties (such as inertia and length) were eliminated by the finite element model itself. The percent relative error between the two methods was approximately 3%, corresponding to the standard deviation of the measured frequencies. For the frequency range considered, the mode shapes were bending modes in two different vibration planes (latero-medial and sagittal), with a slight torsion effect due to the twisted geometry of the tibia. PMID- 1856239 TI - Stress distribution on the cusps of a polyurethane trileaflet heart valve prosthesis in the closed position. AB - In this paper, a finite element analysis of the stress distribution on the cusps of a polyurethane trileaflet heart valve prosthesis in the closed position is presented. The geometry of the valve was modified from a relationship proposed by Ghista and Reul (J. Biomechanics 10, 313-324, 1977). The effects of variations in stent height, leaflet thickness and coaptation area on the stress distribution were also analyzed. Analyses were performed with both rigid and flexible stents for the trileaflet valve in order to delineate the effect of stent flexibility on the leaflet stress distribution. The results showed that regions of stress concentration were present near the commissural attachment similar to those predicted with the bioprostheses. The stresses on the leaflets were reduced by increasing the stent height with both rigid and flexible stents. Selectively increasing the leaflet thickness near the commissures and also increasing the coaptation area did not prove to reduce the leaflet stresses when the stent flexibility was taken into account. The possible effect of high stresses on the structural integrity of polyurethane leaflets and its relationship with calcification is yet to be investigated. PMID- 1856240 TI - Canine intersegmental hip joint forces and moments before and after cemented total hip replacement. AB - Intersegmental forces and moments (i.e. resultant free body forces and moments computed at the joint centers) were studied in canine hindlimbs before and after cemented total hip replacement (THR). Five large, adult, mixed-breed dogs were selected. Their gait was recorded (while leash-walked) before surgery using high speed cinematography and a force plate. Cemented total hip replacement was unilaterally performed on each dog. Gait was again recorded at one and four months after surgery. Segmental properties (mass, center of mass, and mass moment of inertia) of the hindlimbs were experimentally determined, and an inverse dynamics approach was used to compute intersegmental forces and moments in the sagittal plane. Significant reductions in intersegmental joint forces and moments were observed in the operated hindlimb one month after surgery, although kinematic gait parameters were unaltered. Decreases of 77.0% for vertical forces, 61.9% for craniocaudal forces, and 66.2% for extension moments were determined. Four months after surgery, the joint forces and moments had returned to their preoperative values. This experiment demonstrates that the dynamics of normal walking can be restored in a canine model by four months after THR. It also shows that kinetic (rather than kinematic) parameters are more descriptive of antalgic gait in the canine. PMID- 1856241 TI - Three-dimensional numerical analysis of pulsatile flow and wall shear stress in the carotid artery bifurcation. AB - To analyse the pulsatile flow field and the mechanical stresses in a three dimensional carotid artery bifurcation model, computer simulation is applied. The approximation of the Navier-Stokes equations uses a pressure correction finite element method. Numerical results are presented for axial and secondary flow velocity and wall shear stresses with special emphasis on the fluid dynamics in the carotid sinus. This region is of major interest because it is affected preferentially by lesions. Detailed local flow studies as carried out here should lead to a further insight into the mechanisms of atherogenesis. The flow conditions used in the study were chosen according to Ku et al. (Arteriosclerosis 5, 293-302, 1985). The results of this numerical analysis agree in the essential features with their experimental results. PMID- 1856242 TI - Deformation of the distal femur: a contribution towards the pathogenesis of osteochondrosis dissecans in the knee joint. AB - Osteochondrosis dissecans (OD) is a process of subchondral bone necrosis occurring predominantly in young individuals at specific sites. The aetiology of this disease remains controversial with mechanical processes due to trauma and/or ischaemic factors being proposed. This study aims at explaining the aetiology of OD in the knee joint as a result of the particular deformation of the condyles. A finite element analysis of the distal third of the femur was performed. A three dimensional model was developed based on computed tomography scans of a normal femur, consisting of cortical bone, cancellous bone and articular cartilage. This model was subjected to physiological loads at 0, 30, 60 and 90 degrees of knee flexion. A complex deformation was found within each condyle as well as between the two condyles. Both medial and lateral condyles are deformed in the medio lateral direction and at the same time compressed between the patella and the tibia in the antero-posterior direction. This effect is highest at 60 degrees of knee flexion. In both planes, the medial condyle is distorted more than the lateral one. Strain concentration in the subchondral bone facing the patella varies with flexion, especially for angles exceeding 60 degrees. The deformation of the femur in the predominant locus of OD in the medial condyle exceeds that of the lateral condyle considerably. The analysis shows that repeated vigorous exercise including extreme knee flexion may produce rapidly changing strains which in turn could ultimately be responsible for local subchondral bone collapse. PMID- 1856243 TI - Unsteady wall shear stress in a distensible tube. AB - An asymptotic expression of the wall shear stress (WSS) in an elastic tube is deduced for small values of the Womersley parameter. In the case of a rigid tube this asymptotic expression is shown to compare better with the exact solution than Poiseuille's or Lambossy's approximations. Its integration in a one dimensional model of the internal carotid artery blood flow predicts more marked systolic and less marked diastolic WSS than those predicted by the commonly used Poiseuille's approximation. PMID- 1856244 TI - Application of beams on elastic foundation and B-spline solution methodologies to parametric analysis of intramedullary implant systems. AB - A simple numerical technique for parametric evaluation of orthopaedic implant systems, to be used as a screening tool before complex structural analysis (e.g. Finite Element Method), is the subject of this paper. A modified Beams on Elastic Foundation model (with non-constant foundation modulus) is solved using this numerical technique based on B-spline differential equation modelling. A model with variation in the modulus of the foundation, as solved with this spline technique, was compared with a model with constant foundation modulus, solvable with closed form techniques. While deflections were smaller, the reaction force was up to ten times greater for the models with constant modulus of foundation, compared with varying modulus. The model presented in this paper is a refinement of previous models using closed form solution techniques for foundations with constant moduli. It is primarily useful for detecting trends in parametric analyses, or to select specific cases for further analysis by more computationally intensive analytic methods. PMID- 1856245 TI - Comments on "A new theoretical model for noninvasive quantification of mitral regurgitation". PMID- 1856247 TI - Stability of steroid ointments diluted with Compound Zinc Paste B.P. AB - The chemical stability of a range of corticosteroid ointments diluted with Compound Zinc Paste B.P. was studied by high-performance liquid chromatography (HPLC). Betamethasone dipropionate degraded by first-order kinetics at both 25 degrees C and 32 degrees C. At 25 degrees C the mean first-order reaction rate constant was 9.58 x 10(-3)/day, with a t90 (time to reach 90% of the original concentration) of 11.0 days. At 32 degrees C the mean first-order reaction rate constant was 2.42 x 10(-2)/day, with a t90 of 4.4 days. Of the other steroids studied, Fluocinolone acetonide was the least stable, with 33.8% remaining after a 7-day storage period at 25 degrees C. Betamethasone-17-valerate and fluocinonide were of intermediate stability between betamethasone dipropionate and fluocinolone acetonide. None of the steroid ointments studied had adequate stability in Compound Zinc Paste B.P. to allow extemporaneous dilution with this base. PMID- 1856246 TI - Measuring subclinical neuropathy: does it relate to clinical neuropathy? Pittsburgh epidemiology of diabetes complications study-V. AB - We report results from 120 (25- to 34-year-old) participants in a neuropathy substudy of subjects with insulin-dependent diabetes mellitus (IDDM) taking part in a cohort follow-up study. Diabetic neuropathy was evaluated by quantitative sensory testing, nerve conduction studies, and clinical examination. Mean quantitative sensory thresholds differed significantly by clinical category of abnormal sensation and ankle reflex activity. Mean sural and peroneal amplitudes and conduction velocities were also significantly lower for subjects classified as having abnormal ankle reflex activity. Modeling potential correlates in logistic analyses showed glycemic control, triglyceride levels, and hypertension status to be independently associated with clinically overt neuropathy. Similar lipid and hemodynamic parameters were associated with abnormality by any single assessment method used to define neuropathy. Although follow-up is needed to resolve the best assessment methods for determining neuropathy, these results suggest that good glycemic control as well as control of blood pressure and lipids is advisible. PMID- 1856248 TI - Spectrophotometric determination of benzene in ethanol. AB - A rapid, simple spectrophotometric method for the detection and determination of benzene in ethanol is described. Thus, using 1 cm cuvettes and applying the first and/or the second derivative methods, benzene can be determined in ethanol over the concentration range of 5-25 p.p.m. with a CV% less than 1% and with a detection limit of 2 p.p.m. This is considered to be an improvement over the method currently given in the British Pharmacopoeia. PMID- 1856249 TI - Absorption of low and therapeutic doses of ferric maltol, a novel ferric iron compound, in iron deficient subjects using a single dose iron absorption test. AB - Ferric maltol is a novel ferric iron compound with potential use as an oral therapy for iron deficiency anaemia. Using a single, low dose iron absorption test we compared absorption of ferric maltol with absorption of ferrous sulphate in 21 iron deficient subjects. Absorption of 10 mg of ferric maltol as either aqueous solution or a single tablet compared favourably with that of an equivalent dose of ferrous sulphate. At a higher, more therapeutic dose of 60 mg elemental iron as tablets, absorption of ferric maltol appeared to be both more rapid and total absorption greater, than that seen with ferrous sulphate. We conclude that iron from ferric maltol, both at low dose and higher, more therapeutic doses, is at least as well absorbed as from ferrous sulphate. Ferric maltol is the first ferric iron formulation to be absorbed to a degree equivalent to that of ferrous iron salts and may represent a viable form of administration for ferric iron in the treatment of iron deficiency anaemia. PMID- 1856250 TI - The stability of carboplatin, diamorphine, 5-fluorouracil and mitozantrone infusions in an ambulatory pump under storage and prolonged 'in-use' conditions. AB - Drug infusions can be exposed for prolonged periods to 'in-use' conditions where the temperature of an infusion in a holster-worn infusion pump may reach 37 degrees C. In this study, the stability of three cytotoxic drug infusions (carboplatin, 5-fluorouracil and mitozantrone) and one analgesic infusion (diamorphine HCl) was determined in Parker Micropump medication reservoirs under refrigerated storage and prolonged in-use conditions. The stability of the three cytotoxic drug infusions was unaffected by 14 days storage at either 4 or 37 degrees C. The diamorphine HCl infusion was stable over 14 days storage at 4 degrees C but under in-use conditions at 37 degrees C, drug degradation became significant (greater than 5%) if storage exceeded 7 days. PMID- 1856251 TI - Knowledgeable non-compliance with prescribed drugs in elderly subjects--a study with particular reference to non-steroidal anti-inflammatory and antidepressant drugs. AB - Knowledgeable non-compliance with non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressant drugs was investigated in a community-based sample of elderly people. Everyone 70 years and over living in a defined area and taking one of the above drugs, and at least one other prophylactic or symptomatic drug, was studied. Non-steroidal anti-inflammatory drugs and antidepressant drugs are commonly regarded as symptomatic only and knowledgeable non-compliance is consequently high. They are also regarded as less important than drugs which produce no immediate relief of symptoms but which the patient recognizes as needing to be taken regularly to maintain health. In our study, compliance with non-steroidal anti-inflammatory drugs and antidepressant drugs was highest in those who were compliant with a prophylactic drug and were also taking a symptomatic drug. The greater the number of tablets the patient was taking the more likely he or she was to be compliant with the NSAID. Compliance with NSAIDs and antidepressant drugs requires clear label instructions and the patient knowing the purpose of the medication. PMID- 1856252 TI - Pilot study--an investigation of the sources and satisfaction of medication information provided to the elderly. AB - Studies have shown that consumers, in general, do not know everything they should know or would like to know about the medicines they are taking. In addition, several studies report that many older individuals are reluctant to ask questions about the medicines they are taking. This pilot study was conducted to assess the sources from which the elderly obtain their information about prescription and non-prescription medicines and their level of satisfaction with each source. The study results reveal that over half of those surveyed indicated that they received no information about prescription or non-prescription medicines. Further, a large percentage of those surveyed stated that they would like to receive information about non-prescription medicines from a health provider. The findings suggest that pharmacists should routinely provide information to the elderly about all aspects of their medication treatment. PMID- 1856253 TI - Save the Elixir! A pharmaceutical cry from the heartland. PMID- 1856254 TI - The expected impact of managed health organizations on U.S.-based pharmaceutical product development and marketing. PMID- 1856255 TI - A sensitive high-performance liquid chromatographic analysis of propranolol in serum. AB - A rapid and sensitive high-performance liquid chromatographic (HPLC) assay was developed for quantitative determination of propranolol in serum. The assay is performed after single extraction of propranolol and indenolol [internal standard (IS)] from alkalinized serum into ether and eluted from C-18 U Bondapak column with a mobile phase composed of methanol: 0.01 M phosphate buffer pH 3.4 (40:60%, v/v). The column eluant was monitored on a fluorescence detector. Measurement was achieved by taking the peak height ratio of propranolol and comparing it to that of the IS. The detection limit for propranolol in serum is 2.5 ng/ml. Intraday coefficients of variation (CV) ranged from 2.84 to 4.0% and interday (CVs) from 5.8 to 8.4% at three different concentrations. The relative and absolute recoveries varied from 93.8 to 102.3%. Preliminary stability tests showed that propranolol is stable for at least 3 weeks in serum after freezing. The method is applied for the determination of the pharmacokinetic parameters of propranolol after intravenous administration (1 mg/kg) to rabbits. PMID- 1856256 TI - Clinical review 24: Androgens in the aging male. PMID- 1856257 TI - Plasma melatonin as a measure of the human clock. PMID- 1856258 TI - Light exposure induces equivalent phase shifts of the endogenous circadian rhythms of circulating plasma melatonin and core body temperature in men. AB - Release of melatonin into the circulation by the pineal occurs almost exclusively during the nighttime hours. It has been proposed that this daily rhythm, like that of body temperature, reflects the output of a central circadian pacemaker in humans. In order to investigate the relationship of the circadian rhythms of body temperature and melatonin in humans and compare their resetting responses to light, we characterized the endogenous 24-h profiles of these rhythms in eight young male adults during constant routines before and after exposure to a stimulus consisting of bright light, room light, and darkness/sleep. We found that the time of the fitted maximum of the endogenous melatonin rhythm consistently preceded the fitted temperature minimum by a mean +/- SE of 1.8 +/- 0.2 h. Bright-light exposure induced substantial and equivalent phase shifts of the melatonin and temperature rhythms (mean +/- SE difference in the phase shifting response, 0.03 +/- 0.32 h), and the body temperature and melatonin rhythms thus maintained their usual phase relationship even after light-induced circadian phase inversion. These results are consistent with the hypothesis that the endogenous circadian components of both the plasma melatonin and body temperature rhythms are generated by a single central circadian pacemaker in humans. Furthermore, using the time of the fitted temperature minimum as a reference standard, we found that the fitted maximum of the endogenous 24-h melatonin profile was a more reliable phase marker than the onset of the nocturnal rise of melatonin (F = 4.48; P less than 0.01). PMID- 1856259 TI - The incidence of thyroid stimulating blocking antibodies during the hypothyroid phase in patients with subacute thyroiditis. AB - The etiology of subacute (de Quervain's) thyroiditis (SAT) is uncertain, although it probably represents a nonspecific inflammatory response by the thyroid to a variety of viruses. It has been suggested that nonimmune processes are involved in SAT patients who have negative autoantibody titers. The disease has a variable course; although it is self-limited in most cases, some patients develop transient hypothyroidism, and others do not during the recovery period. The present study was performed to evaluate the occurrence of TSH receptor antibody (TRAb), measured by RRA (TSH binding inhibitor), TRAb measured by stimulation assay (thyroid-stimulating antibody), and TRAb measured by blocking assay [TSH blocking antibody (TSH-BAb)] activity in 68 patients with SAT who had negative autoantibody titers. The patients were divided into 2 groups: group I, 31 patients who developed hypothyroidism during the recovery period; and group II, 37 patients who remained euthyroid during recovery. Positive immunoglobulin activity occurred in about 20% of group I patients during follow-up, but in only 3% of group II patients. About 20% of group I patients developed positive TSH-BAb activity and were hypothyroid, requiring exogenous hormone therapy for 1.2-3.5 yr, whereas hypothyroidism was relatively transient in group I patients who had negative TSH-BAb activity (2-6 months). Although increased TSH-BAb activity may account for hypothyroidism in some patients with SAT, the precise mechanism for the development of transient hypothyroidism in SAT remains enigmatic. PMID- 1856260 TI - Parathyroid hormone increases epidermal growth factor receptors in cultured human trophoblastic cells from early and term placenta. AB - The effect of PTH on the epidermal growth factor (EGF) receptor was analyzed during the in vitro differentiation of human cytotrophoblasts. The cytotrophoblasts were isolated by a trypsin-DNase method from first trimester and term placentas and purified on a Percoll gradient. In culture, these cells aggregated and fused together to form a syncytium. This in vitro differentiation was associated with a 2-fold increase in 125I-EGF binding after 48 h of culture. The addition of 0.1 microM PTH (PTH-treated cells) to the culture medium induced a significant 2- to 3-fold increase (P less than 0.005) in EGF binding. The effect was dose related with a maximum obtained at a 1 nM concentration. Scatchard analyses revealed that PTH-treated cells possess a 2-fold higher number of high affinity sites as compared to control cells from early placenta (0.71 +/- 0.06 pmol/mg protein and 0.34 +/- 0.04 pmol/mg protein, respectively) and from term placenta (1.24 +/- 0.10 pmol/mg protein and 0.61 +/- 0.07 pmol/mg protein, respectively). The apparent Kd values for high affinity sites (0.15 nM) and for low affinity sites (4 nM) were not altered either by the gestational age of the cells or by PTH treatment. With respect to the EGF-dependent phosphorylation in membranes of trophoblast cells in culture, it was found that the phosphorylation of two major proteins of 175 kilodaltons and 35 kilodaltons, is greatly increased in PTH-treated cell membranes in the presence of EGF. This PTH-induced effect on EGF receptors was associated with an augmented functional response of trophoblastic cells to EGF. PTH increased the EGF-stimulated secretion of hCG. These results demonstrate that PTH increases the number of biologically active EGF receptors during the in vitro differentiation of human trophoblast cells. This PTH-induced effect suggests a role for this hormone in the regulation of the growth and the endocrine functions of these cells. PMID- 1856261 TI - Glucocorticoids inhibit lipopolysaccharide-induced production of tumor necrosis factor-alpha by human fetal Kupffer cells. AB - Inflammatory mediators, such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) are secreted by fixed tissue macrophages and exhibit local autocrine and paracrine effects as well as distant endocrine effects. Human fetal Kupffer cells, the fixed tissue macrophages of the liver, may play a role as modulators of immune and endocrine function in early embryonic and fetal development. In the present study we isolated human fetal Kupffer cells to greater than 90% purity and prepared short term cultures to investigate the effect of glucocorticoids on the secretion of the cytokine TNF alpha. Fetal Kupffer cells secreted TNF alpha and IL-1 beta after culture with bacterial lipopolysaccharide (LPS), indicating that these cells express mature macrophage function. Cortisol and dexamethasone dramatically suppressed the LPS-stimulated secretion of TNF alpha by fetal Kupffer cells. The inhibitory effects of glucocorticoids appeared to be specific, since estrogen, progesterone, and testosterone had no effect on LPS stimulation of TNF alpha production. None of the steroids tested altered basal production or enhanced the LPS-stimulated production of TNF alpha by fetal Kupffer cells. The inhibition by glucocorticoids could be reversed by the addition of RU 486, indicating that this effect was mediated by the glucocorticoid receptor. These results demonstrate that human fetal macrophages demonstrate mature macrophage function in early gestation; they can be activated to produce TNF alpha by a well characterized modulator of cellular function (LPS) and suppressed by glucocorticoids. PMID- 1856262 TI - Growth hormone (GH) responses to the hexapeptide GH-releasing peptide and GH releasing hormone (GHRH) in the cynomolgus macaque: evidence for non-GHRH mediated responses. AB - GH-releasing peptide (GHRP; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2), a hexapeptide derived from enkephalin, has been shown to have GH-releasing activity in man and several animal species. To characterize the GHRP dose-response curve and compare it with that of GH-releasing hormone [GHRH-(1-44)NH2], six unanesthetized young adult cynomolgus macaques were tested with a range of iv doses of GHRP or GHRH in random order. Animals were fitted with vests and tethers. Blood samples were obtained before and at 15-min intervals after the administration of drugs. Doses ranged from 0.03-3 mg/kg for GHRP and from 1-30 micrograms/kg for GHRH. The dose response curves for the two peptides were not parallel. GHRP had lower potency, but evoked a much higher peak GH response than GHRH (greater than 55 vs. 12 micrograms/L). Because one of the proposed mechanisms of action of GHRP is the inhibition of somatostatin (SS), we tested the effects of propranolol, which inhibits SS, on the GH responses to GHRH and GHRP. Propranolol was given at a dose of 14 micrograms/kg, iv, 10 min before the injection of saline, GHRH (10 micrograms/kg), or GHRP (1 mg/kg). GH responses to propranolol alone did not differ from those to placebo (peak, 6 +/- 2 vs. 8 +/- 2 micrograms/L). However, propranolol pretreatment doubled the GH responses to both GHRH and GHRP compared with those to GHRH or GHRP alone 28 +/- 5 micrograms/L vs. 14 +/- 5 (P less than 0.05) and 54 +/- 2 vs. 25 +/- 6 micrograms/L (P less than 0.001), respectively]. These results show that GHRP causes a potent dose-dependent release of GH in this primate species. Since GHRP can produce a greater maximal GH response than GHRH, mechanisms other than release of endogenous GHRH must be involved. PMID- 1856263 TI - Androgen resistance associated with a mutation of the androgen receptor at amino acid 772 (Arg----Cys) results from a combination of decreased messenger ribonucleic acid levels and impairment of receptor function. AB - Analysis of the nucleotide sequence of the coding segment of the androgen receptor gene in a patient (N105) with the receptor-negative form of complete testicular feminization has revealed a single substitution (CGC----TGC) at nucleotide 2476. This alteration results in the conversion of an arginine at amino acid 772 to a cysteine. Introduction of this mutation into an androgen receptor cDNA and transfection of the mutant cDNA into COS cells result in the production of a receptor protein with an alteration in the apparent Kd of ligand binding (3 nM) compared to that of the normal androgen receptor (0.5 nM). The mutant receptor protein predicted for patient N105 also demonstrates thermal instability of ligand binding that is not associated with quantitative or qualitative changes in the immunoreactive androgen receptor protein. When assayed in cotransfection experiments using a mouse mammary tumor virus-chloramphenicol acetyl transferase reporter system, the N105 receptor protein appears to be about a tenth as active as the control receptor. These functional characteristics do not appear sufficient to account for the phenotype of complete testicular feminization and do not explain the profound deficiency of androgen receptor in cultured skin fibroblasts. Quantitative S1 nuclease protection assays reveal that the level of androgen receptor mRNA in fibroblasts from patient N105 is markedly reduced. These results suggest that the phenotype in patient N105 is due to two effects of the nucleotide substitution at residue 2476: the replacement of a crucial amino acid (772) in the hormone-binding domain that impairs the function of any receptor molecules formed and a decrease in the level of androgen receptor mRNA. PMID- 1856264 TI - Regulation of 11 beta-hydroxysteroid dehydrogenase activity in human skin fibroblasts: enzymatic modulation of glucocorticoid action. AB - The regulation of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) was studied in cultured human skin fibroblasts. 11-Oxo-reductase activity was 5- to 10-fold higher than 11 beta-dehydrogenase activity. Cells treated with 100 nM dexamethasone (Dex) showed a 3-fold increase in the maximum velocity of both activities without a change in the Km values. Dex induction of 11 beta HSD was half-maximal at 48 h and was blocked by glucocorticoid receptor antagonists. Nonglucocorticoid steroids were ineffective. Removal of serum from the culture medium increased maximum velocity values up to 6-fold. Treatment of cells grown in the absence of serum with 8-bromo-cAMP, phorbol esters, or insulin decreased both 11 beta HSD activities. The effects of Dex treatment and serum removal were additive and were blocked by cycloheximide and actinomycin-D. In all experiments both 11 beta HSD activities were modulated in parallel. Both cortisone (200 nM) and cortisol increased the aromatase activity of fibroblasts in the presence of serum. Prior induction of 11 beta HSD by serum removal increased the potency of cortisone from 10-15% to 50% that of cortisol. We conclude that 1) in human fibroblasts 11 beta HSD appears to be a single protein that is under multifactorial regulation; 2) 11 beta HSD may increase or decrease cortisol availability to glucocorticoid receptors; and 3) plasma cortisone levels may be important in assessing glucocorticoid status. PMID- 1856265 TI - Characteristics of growth hormone binding to liver microsomes of pregnant women. AB - Specific binding of hGH to liver microsomes of nonpregnant women and men is low, usually 10% of less in RRA. In pregnant women, however, we found that this binding is 10 times higher. The binding reaction shared the properties common to receptor systems: time, temperature and cation dependence, saturability and reversibility, hGH specific binding without cations was 10 times lower. The cross reactions of hPRL and human placental lactogen with hGH were 0.49 +/- 0.16% and 0.10 +/- 0.05%, respectively. 125I-hPRL and 125I-human placental lactogen binding to microsomes of two controls and two pregnant women were very low and poorly reproducible. The Scatchard analysis revealed two hGH binding sites, one with an association constant (KA) of 2.7 +/- 0.1 x 10(10) M-1, and the other with a KA of 1.5 +/- 0.1 x 10(9) M-1. In one nonpregnant woman, we found a single hGH binding site with a KA of 1.5 x 10(9) M-1, confirming results previously reported in the literature. A hGH RRA was set up with microsomes of pregnant women. Acromegalic sera produced curves parallel to the hGH standard and pituitary dwarf serum had no 125I-hGH displacing activity. Sera of pregnant women produced curves divergent to the hGH standard and showed a 125I-hGH displacing activity 20 to 40 times higher than could be predicted by hGH levels determined by RIA. Cord sera and sera from puerperal women had similar hGH levels as determined by either RRA or RIA (r = 0.93, P less than 0.001, slope = 0.85, n = 25). Our results show the existence of specific GH receptors and serum factor(s) with high 125I-hGH displacing activity from these receptors in pregnancy. These findings must be related to several metabolic changes of pregnancy, such as glucose intolerance, hyperinsulinemia, increased lipolysis, and ketogenesis. PMID- 1856266 TI - Normal bone density of the wrist and spine and increased wrist fractures in girls with Turner's syndrome. AB - Turner's syndrome is associated with multiple skeletal abnormalities, including osteoporosis. We evaluated the hypothesis that girls with Turner's syndrome may have deficient bone density before the expected age of pubertal onset (9-13 yr) by comparing the bone mineral content of the wrist and lumbar spine in 78 girls with Turner's syndrome (4-13 yr old) and 28 normal prepubertal girls who were matched for age, bone age, body mass index, or height age. The bone mineral content of the wrist and spine was measured by single photon absorptiometry (SPA) and dual photon absorptiometry (DPA), respectively. SPA values for girls with Turner's syndrome vs. normal subjects (4-6.9, 7-9.9, and 10-12.9 yr old) were (mean +/- SD) 0.27 +/- 0.05 vs. 0.36 +/- 0.05, 0.35 +/- 0.06 vs. 0.41 +/- 0.06, and 0.41 +/- 0.05 vs. 0.45 +/- 0.03 g/cm2, respectively. SPA values in the Turner's syndrome girls were decreased compared to those in normal prepubertal girls, matched for age (P less than 0.0001), bone age, (P less than 0.001), and body mass index (BMI; P less than 0.0001), but not for height age. DPA values for girls with Turner's syndrome vs. normal girls in the same age categories were 0.65 +/- 0.06 vs. 0.70 +/- 0.09, 0.77 +/- 0.08 vs. 0.79 +/- 0.09, and 0.83 +/- 0.12 vs. 0.78 +/- 0.07 g/cm2. DPA values in Turner's syndrome girls (as a group) were decreased compared to those in normal prepubertal girls matched for age (P less than 0.05) and BMI (P less than 0.02), but not for bone age or height age. The annual incidence rate of wrist fractures in Turner's syndrome girls (9.1 of 1000) was significantly increased compared to the reported annual incidence rate in normal children (3.5 of 1000; P less than 0.003). We conclude that prepubertal aged girls with Turner's syndrome (less than 13 yr old) have normal bone density for height age, but significantly decreased bone density of the wrist for chronological age, bone age, and BMI. They also have significantly more wrist fractures than normal girls, but it is not clear that this is related to their bone density. PMID- 1856267 TI - Proopiomelanocortin gene expression in normal and tumoral human lung. AB - Proopiomelanocortin (POMC) gene expression is not restricted to the pituitary corticotroph cell, but also takes place in many normal and tumoral nonpituitary tissues. In contrast, the ectopic ACTH syndrome is a rare event. Because it is most often associated with lung tumors, we specifically studied this tissue, analyzing the different forms of POMC RNAs in normal specimens as well as in various types of tumors. The endocrine nature of the tumors was assessed by both histological examination and measurements of secretogranin-I fragments in the tissue extracts. POMC RNA was first detected by Northern blot analysis; its absolute amounts and its various molecular forms were more precisely quantified and discriminated by S1 mapping studies using a single stranded DNA probe located at the 5' end of exon 3. In five bronchial carcinoid tumors associated with the ectopic ACTH syndrome, a highly predominant, if not single, POMC RNA identical to the 1200-nucleotide (nt) pituitary message was present, the high amounts of which were correlated with those of POMC peptides in the same tissues. In five bronchial carcinoid tumors not associated with the ectopic ACTH syndrome, the same message was detected (four of five), with a second, often predominant, short RNA of about 800 nt (five of five), and the overall amounts of POMC RNAs were low. Similar patterns of POMC RNAs were observed in squamous cell tumors, adenocarcinomas, and normal lung, where the short 800-nt RNA tended to be predominant. These results show that POMC gene expression can be demonstrated in normal lung tissue and in all types of lung tumors. The ectopic ACTH syndrome only occurs with tumors capable of generating high amounts of the pituitary-like message, a phenomenon that seems to be restricted to an occasional tumor with features of neuroendocrine differentiation. PMID- 1856268 TI - Spontaneous growth hormone secretion increases during puberty in normal girls and boys. AB - To test the hypothesis that GH secretion increases during puberty, we measured GH levels in samples obtained every 20 min for 24 h from 132 normal children and adolescents. In both girls and boys, GH levels increased during puberty. The increase in mean levels was earlier in girls than boys, was most evident at night, and was due to increased pulse amplitude rather than a change in pulse frequency. The mean nighttime GH level in girls with bone ages (BA) greater than 12 to 14 yr were significantly greater than the mean level in girls with BA less than 8 yr (7.3 +/- 3.0 vs. 3.4 +/- 1.7 micrograms/L; P less than 0.01) and were greatest at breast stage 3 (7.9 +/- 2.5 micrograms/L). GH pulse amplitude increased significantly before pubertal onset in girls and was significantly greater at BA greater than 12 to 14 yr than at BA of 8 yr or less (13.9 +/- 6.0 vs. 7.9 +/- 4.8 micrograms/L; P less than 0.01) and greatest at breast stage 3 (15.0 +/- 6.3 micrograms/L). The pubertal increase in GH secretion was delayed in boys compared to girls, with the lowest mean 24-h GH and mean nighttime GH values in boys with BA greater than 8 to 11 yr. The mean nighttime GH level at BA greater than 11 to 13 yr in boys was significantly greater than that in the boys with BA greater than 8 to 11 yr (5.8 +/- 2.9 vs. 3.5 +/- 2.1 micrograms/L; P less than 0.05) and was greatest at a testicular volume of more than 10 to 15 mL (6.5 +/- 2.0 micrograms/L). The mean nighttime GH pulse amplitude in boys was significantly greater at BA greater than 11 to 13 yr than at BA greater than 8 to 11 yr (13.9 +/- 5.7vs. 7.3 + 2.6 micrograms/L, P less than 0.05) and was greatest at a testicular volume greater than 20 mL (15.8 +/- 12.0 micrograms/L). The mean nighttime GH levels correlated inversely with body mass index in both sexes, although the correlation achieved statistical significance only for the girls, being stronger in breast stage 3 to 5 girls (r = -0.57 P = 0.0007; n = 32) than in stage 1 and 2 girls (r = -0.38; P = 0.03; n = 32). These observations in normal adolescents emphasize the importance of interpreting spontaneous GH levels in short children in relation to normative data appropriate for sex, body mass, and bone age or pubertal stage. PMID- 1856269 TI - Renin increases human amnion cell prostaglandin E2 biosynthesis. AB - Chorionic cells are known to produce several protein hormones; among them is prorenin/renin, whose function is unknown at this time. Amnion is contiguous with chorion and plays a part in the mechanism(s) of parturition through increased prostaglandin (PG) production. The purpose of the present study was to determine whether renin has any action on amnion cell PGE2 biosynthesis. Amnion cells in primary monolayer culture were incubated for 16 h with increasing concentrations of renin. Renin induced a concentration-dependent increase in amnion cell PGE2 production (e.g. in picograms of PGE2 per microgram protein/16 h; mean +/- SEM; n = 4; control, 3.01 +/- 0.15; 0.0001 U/mL renin, 9.66 +/- 2.0; 0.001 U/mL renin, 10.36 +/- 1.91; 0.01 U/mL renin, 10.3 +/- 3.36; 0.1 U/mL renin, 13.82 +/- 2.1). Significant stimulation of amnion cell PGE2 by renin is not observed until 2 h of incubation; stimulation continues a further 6 h, with little change in the following 8 h. We tested the possibility that renin's stimulatory effects were due to angiotensin-I (AI) and angiotensin-II (AII) formation by testing the effects of AI and AII directly and that of renin in the presence of saralasin, a potent antagonist of AII action. Saralasin did not inhibit the effect of renin, nor was AI or AII alone (10(-10)-10(-6) M) stimulatory. Thus, we believe that chorionic renin may have a novel role in the regulation of amnion cell PGE2 production that is independent of angiotensin formation. PMID- 1856271 TI - Citation for the Richard E. Weitzman Memorial Award of The Endocrine Society to Synthia H. Mellon. PMID- 1856270 TI - Citation for the Rorer Pharmaceutical Clinical Investigator Award of The Endocrine Society to Lawrence A. Frohman. PMID- 1856272 TI - Citation for the Edwin B. Astwood Lectureship of The Endocrine Society to Marc E. Lippman. PMID- 1856273 TI - Citation for the Robert H. Williams Distinguished Leadership Award to William D. Odell. PMID- 1856274 TI - Citation for the Ernst Oppenheimer Award of The Endocrine Society to Perrin C. White. PMID- 1856275 TI - Citation for the Fred Conrad Koch Award of The Endocrine Society to John T. Potts, Jr. PMID- 1856276 TI - Citation for the Distinguished Service Award of The Endocrine Society to Francine L. Trull. PMID- 1856277 TI - A new measurement of profile esthetics. PMID- 1856278 TI - Measuring symptom severity with the TMJ scale. PMID- 1856279 TI - Working with an interior decorator. PMID- 1856280 TI - Accessory aligning wires in double molar tubes. PMID- 1856281 TI - Adult nonextraction treatment with a Jasper Jumper. PMID- 1856282 TI - Don't force it. PMID- 1856284 TI - Use of information technology for auditing effective use of laboratory services. PMID- 1856283 TI - Screening for presymptomatic disease. PMID- 1856285 TI - Expression of intrahepatic hepatitis D viral antigen in chronic hepatitis D virus infection. AB - To elucidate the biological importance of intrahepatic hepatitis D virus antigen, its expression was correlated with biochemical and histological inflammatory activity in 98 biopsy specimens from 68 patients seropositive for total antibody to the virus. Seventy five specimens were positive for intrahepatic nuclear antigen for HDV antigen accompanied by cytoplasmic HDV antigen in only one biopsy specimen. This group had significantly higher serum transaminase activities and inflammatory activity than the remaining cases that were negative for HDV antigen. Among the group positive for HDV antigen, there was no correlation between the proportion of hepatocytes containing HDV antigen and either serum transaminase activity or histological inflammatory indices. In 22 HDV antigen positive patients who had follow up biopsy specimens taken at a median of two years, the proportion with cirrhosis increased from 36% to 73%. Serum transaminase activities remained the same during this period, but the proportion of HDV antigen positive cells dropped. Follow up of 51 patients showed that 21 died or underwent liver transplantation within three years. The absence of an association between intrahepatic HDV antigen expression and progression of histological liver damage does not support the view that HDV is directly cytopathic to hepatocytes. Immune mediated mechanisms may have a role in the pathogenesis of chronic liver disease related to HDV infection. PMID- 1856287 TI - Histological diagnosis of intestinal microsporidiosis in patients with AIDS. AB - Fifty nine patients seropositive for human immunodeficiency virus (HIV) and diarrhoea and 20 with weight loss were investigated for microsporidiosis using light and electron microscopical examination of duodenal and jejunal biopsy specimens. Eight cases of microsporidiosis were found, in five of whom it was the sole pathogen. In all eight cases the organism was identified at light microscopy without prior knowledge of the electron microscopical findings. All stages of the life cycle are best seen in resin sections cut at 1 micron and stained with Giemsa, but spores could easily be identified in paraffin sections cut at 5 microns and stained with haematoxylin and eosin. In all cases the parasite was identified both in duodenal pinch and jejunal "Crosby" capsule biopsy specimens. All cases of microsporidiosis occurred in patients with diarrhoea. Both electron and light microscopical examination suggested that the pathogenic mechanism involves the shedding of infected enterocytes containing large numbers of spores. It is suggested that the optimal way to diagnose microsporidiosis is by light microscopical examination of duodenal pinch biopsy specimens. PMID- 1856286 TI - Detection of hepatitis B virus pre-S1 and pre-S2 determinants in paraffin wax embedded liver tissue: importance of reagents used. AB - The presence of pre-S polypeptides in paraffin wax embedded liver sections from the biopsy specimens of 15 hepatitis B surface antigen (HBsAg) seropositive patients (five with chronic persistent hepatitis (CPH), four with chronic active hepatitis (CAH), four with cirrhosis and two "healthy" HBsAg carriers) was investigated using monoclonal antibodies directed to distinct epitopes on pre-S1 (18/7 and TO 606) and pre-S2 (5535 and Q 19/10). Pre-S1 was found in 13 cases when MA 18/7 was used but in only one specimen when TO 606 was used. Pre-S2 was detected in all the biopsy specimens with 5535 and in eight samples with Q 19/10. Mild enzymatic digestion annulled the staining of all monoclonal antibodies but Q 19/10. No association was observed between pre-S polypeptide expression and hepatitis B virus (HBV) replication or disease severity. Pre-S polypeptides can be detected readily in paraffin wax embedded material but the results obtained largely depend on the monoclonal antibodies used. PMID- 1856288 TI - Detection of Chlamydia trachomatis DNA in patients with non-gonococcal urethritis using the polymerase chain reaction. AB - A practical protocol using the polymerase chain reaction (PCR) was designed for detecting Chlamydia trachomatis in clinical samples. DNA was extracted from material collected on urethral swabs and used as substrate for the PCR. The target was a 600 basepair DNA segment of the multicopy plasmid that is common to all strains of the bacterium. Negative samples were checked for loss of DNA or presence of polymerase inhibitors by a second PCR, targeted to a conserved segment of the human genome. The whole procedure was tested on 216 men with non gonococcal urethritis (NGU). All patients were independently assessed by tissue culture isolation (60 positive samples) and a commercial immunoenzymatic assay. The PCR protocol, while sufficiently simple for routine application, was reliable and, for the diagnosis of urethritis, at least as good as tissue culture isolation. PMID- 1856289 TI - Comparison of IgG antibody profiles by immunoblotting in patients with acute and previous Toxoplasma gondii infection. AB - The IgG antibody profile to Toxoplasma gondii proteins of less than 37 kilodaltons in sera from patients with acute and previous infection was studied by immunoblotting. Bands at 28, 29, and 36 kilodaltons were more common in acute infection (10 out of 10, nine out of 10, and nine out of 10, respectively) compared with previous infection (five out of 10, four out of 10, and one out of 10, respectively). The 6 kilodalton band was present in 10 out of 10 sera from patients with acute infection and five out of 10 sera from those with previous infection. A new observation is a doublet of bands of 22-25 kilodaltons present only in sera from patients with acute infection. This doublet may be a more reliable indicator of acute infection than the 6 kilodalton band. PMID- 1856290 TI - Endocardial fibroelastosis in infants with hydrops fetalis. AB - Endocardial fibroelastosis, defined as an endocardium in excess of 30 microns thick, was found in 10 out of 34 cases of hydrops fetalis in a review of 1589 perinatal necropsies carried out between 1976 and 1989. The infants comprised 16 cases of rhesus haemolytic disease, of whom three had endocardial fibroelastosis, and 18 cases of non-rhesus hydrops, of whom seven had endocardial fibroelastosis. Intrauterine congestive heart failure was thought to have been the probable cause of hydrops in eight of the 10 infants with endocardial fibroelastosis. None of an age matched control group without endocardial fibroelastosis had evidence of congestive cardiac failure. These observations support the hypothesis that endocardial fibroelastosis is an endocardial response to chronic prenatal myocardial stress. PMID- 1856291 TI - Expression of neural cell adhesion molecule (NCAM) isoforms in neuroblastoma. AB - A comparative study on the expression of the neural cell adhesion molecule (NCAM) in human neuroblastoma cell lines and tissues was undertaken. NCAMs are a family of closely related cell surface glycoproteins involved in cell-cell interactions. Using antibodies that recognise distinct epitopes on NCAM, their presence was shown in neuroblastoma, but these studies do not yield any information on the specific NCAM isoforms associated with the tumour. Western and Northern blot analyses were therefore carried out to characterise the NCAM isoforms in this neuroectodermal tumour. Western blot studies using the monoclonal antibody ERIC-1 showed that all human neuroblastoma cell lines tested expressed the 140 and 120 kilodalton isoforms of NCAM in their desialo state. Some of the cell lines also expressed NCAM-180. The data are corroborated by Northern blotting where a transcript of 7.4 kilobase pairs was identified only in lines expressing NCAM 180; the 6.7 and 5.4 kilobase pair transcripts coding for 140 and 120 kilodalton isoforms, respectively, were present in all the cell lines tested. The NCAM isoforms identified in neuroblastoma were also different from those found in adult and fetal brain tissue, suggesting that aberrations are expressed in the molecule during tumorigenesis. PMID- 1856292 TI - Microbiological assay for vitamin B12 performed in 96-well microtitre plates. AB - A simplified microbiological assay for vitamin B12 estimation, completed on microtitre plates using a colistin sulphate resistant strain of Lactobacillus leichmannii (NCIB 12519), and cryopreserved cultures is described. The new assay correlated well with a more conventional "tube" assay and was not influenced by the presence of antibiotics in serum. Evaluation of assay performance showed excellent interassay and intra-assay precision with quantitative recovery of added cyanocobalamin over a wide range of additions (94.9%-102.1%). The advantages of short incubation time, easy reading, and minimal reagent costs make this assay an attractive option in the routine clinical laboratory and in research. PMID- 1856293 TI - Serum C-reactive protein and neopterin concentrations in patients with viral or bacterial infection. AB - Serum C-reactive protein and neopterin concentrations were measured in samples taken at an early stage in different types of infection to see whether the combination of markers could contribute to the diagnosis of infection and help distinguish between bacterial and viral infections, tuberculosis, and infections due to "other" pathogens. Both markers were significantly raised in all categories of infection compared with controls, and there were significant differences between the means of both markers when comparing several of the categories of infection. Only C-reactive protein concentrations in bacteraemic patients, however, were both sensitive and specific at distinguishing the type of infection. The additional use of neopterin estimation played only a minor part in increasing the specificity of diagnosis in tuberculosis and in viral infections. On the basis of this study it was not considered worth the time and expense of performing neopterin assays in addition to C-reactive protein estimations to differentiate viral from bacterial infection. PMID- 1856294 TI - Role of mesothelial cells in peritoneal antibacterial defence. AB - Whether phagocytosis of Staphylococcus aureus by polymorphonuclear neutrophils, monocytes, and peritoneal macrophages takes place when the staphylococci are adherent to monolayers of human mesothelial cells in the absence of opsonins was investigated. Adherence of S aureus to mesothelial monolayers increased significantly when the bacteria were opsonised with pooled human serum, but phagocytosis by polymorphonuclear neutrophils and monocytes occurred independently. Phagocytosis by peritoneal macrophages, however, was only marginal. Pretreatment of polymorphonuclear neutrophils with inhibitors of cellular metabolism and motility reduced their phagocytic capacity. These results indicate that the surface of mesothelial cells provides favourable conditions for the elimination of staphylococci in the peritoneal cavity. Phagocytic motility seems to be important in surface phagocytosis. The inability of peritoneal macrophages to phagocytise staphylococci adherent to the mesothelial cells suggests that they contribute little to the antibacterial defence of the peritoneal membrane of patients receiving peritoneal dialysis. PMID- 1856295 TI - Extracting, storing, and transporting whole blood DNA under tropical conditions. AB - A simple and robust technique for the extraction of DNA under tropical field conditions is described. It requires minimal equipment and is based on lysing cells in whole blood and precipitating the nuclei containing the DNA by centrifugation. The DNA solution can be stored in guanidinium buffer for many months without being refrigerated. Further purification of the DNA can then be carried out in a laboratory with facilities for ultracentrifugation by banding the DNA through cesium chloride. This method yields DNA of sufficient quality and purity for Southern blotting and probing and alleviates the need to transport whole blood between different countries and laboratories. PMID- 1856296 TI - Detection of Borrelia burgdorferi in patients with Lyme disease by the polymerase chain reaction. AB - Borrelia burgdorferi, the causative agent of Lyme disease, was detected in patients' serum by DNA amplification using the polymerase chain reaction (PCR). B burgdorferi was pelleted from serum samples by centrifugation (10,000 x g for 10 minutes) and lysed by treatment with ammonium hydroxide (100 degrees C for 15 minutes). Two pairs of "nested" PCR primers complementary to the gene encoding a major outer surface protein (OSP A) of B burgdorferi were used in DNA amplification under standard PCR conditions (Perkin-Elmer Cetus). Two out of five patients with erythema migrans, the characteristic primary skin lesion associated with early Lyme disease, were positive by the PCR. This method could form the basis of a useful routine laboratory test in those cases of early Lyme disease where conventional serological testing commonly yields equivocal or false negative results. PMID- 1856298 TI - Measurement techniques for melanoma: a statistical comparison. PMID- 1856297 TI - Helicobacter pylori and gastric histamine concentrations. AB - An enzyme isotopic assay was used to determine the histamine concentration in the gastric mucosa of patients positive for Helicobacter pylori with (n = 11) and without duodenal ulceration (n = 9) and in negative controls (n = 7). A significant difference was observed when the histamine content of H pylori negative subjects was compared with that of positive patients. On the other hand, there was no significant difference in histamine concentration between H pylori positive patients with duodenal ulceration and those without duodenal ulceration. H pylori positive patients with and without duodenal ulceration had significantly lower gastric histamine concentrations than H pylori negative subjects. The lower gastric histamine concentration observed in H pylori positive patients might be due to increased histamine release which could in turn induce increased gastric acid secretion. PMID- 1856299 TI - Survey of GPs' attitudes to microbiology services. PMID- 1856300 TI - Accreditation of clinical pathology laboratories in the United Kingdom: the story so far. PMID- 1856301 TI - The effect of a cognitive behavioral intervention on oral hygiene. AB - Several medical areas that require patient compliance have successfully used psychological interventions emphasizing cognitive behavioral components. However, there are no published reports on the effect of cognitive behavioral interventions on oral hygiene in adults using an experimental design. For this study, 100 male veterans age 21-65 years were randomly assigned to 4 groups (cognitive behavioral, education, attention control, and control); to compare the effectiveness of these interventions on oral hygiene, a 5-week pre-test-post-test design was utilized. The dependent variables were self-report of brushing and flossing behavior and dental plaque levels utilizing the plaque index. After the interventions, there was only one significant difference between the control and the experimental groups for brushing frequency. There were no significant differences among the experimental groups for this intervention. The self-report of flossing frequency significantly increased in all 3 treatment groups, but there were no significant differences between these groups. In addition, plaque levels decreased significantly in all 3 experimental groups. Plaque levels in the cognitive behavioral group were significantly lower than those of the educational group. It was not possible to determine whether the greater plaque reduction in the cognitive-behavioral group could be attributed to the nature of the intervention or to the extra time spent with patients in the cognitive behavioral group. PMID- 1856302 TI - Marginal alveolar bone height in an adult Swedish population. A radiographic cross-sectional epidemiologic study. AB - The purpose of the present cross-sectional epidemiologic study was to assess the interproximal alveolar bone level within the dentition of 732 randomly selected adult individuals, stratified according to gender and age. Full mouth series of periapical radiographs were used for the assessments of the relation alveolar bone height/root length (B/R). A computer/digitizer recording method was utilized for the assessments. The results were presented as (i) mean values per age group and gender, (ii) mean frequency of subjects with sites exceeding certain thresholds of bone loss and (iii) cumulative frequencies of subjects with various number and percentual proportion of sites in relation to different B/R-ratio intervals. The results showed a reduction in mean alveolar bone/root ratio with age. The women had a significantly more favourable mean B/R-ratio than men in the ages above 40 years; the women had, however, more missing sites above age 60 years. By older age, there was observed an increased variation between individual mean B/R-ratios. Only a few subjects had a mean B/R-ratio less than or equal to 50%. A subfraction of the subjects in the different age groups had greater than 20% of their sites below a B/R-ratio of 60%. This fraction increased with age. PMID- 1856303 TI - Short-term effects of initial periodontal therapy (hygienic phase). AB - The aim of the present study was to evaluate the effect of non-surgical periodontal therapy on probing pocket depths and probing attachment levels using a patient group with moderate to advanced periodontitis. 68 patients with moderate to advanced periodontitis underwent hygienic phase therapy including oral hygiene instructions, scaling and root planing and elimination of plaque retentive factors. Assessments of the plaque control record (PCR), bleeding on probing (BoP), probing depths and probing attachment levels were performed at baseline examination and 3 to 5 months following active treatment. The measurements were obtained at 4 interproximal aspects of each tooth with a thin calibrated probe. Mean BoP values decreased from 63.2 +/- 21.9% at baseline to 16.6 +/- 7.3% after therapy, and mean PCR decreased from 78.6 +/- 16.4% to 12.7 +/- 7.1%, respectively. A reduction in mean probing pocket depth from 3.96 +/- 1.39 mm at baseline to 3.30 +/- 1.16 mm after therapy was noted. Sites with initial probing depths of 1-3 mm showed no change, sites with initial values of 4 6 mm revealed a reduction of 1.03 +/- 1.04 mm, while initial pockets of 7-9 mm decreased in depth by 2.28 +/- 1.62 mm. A gain in the mean probing attachment level from 4.16 +/- 1.80 mm to 3.74 +/- 1.71 mm was observed as a result of treatment. The group with the shallow initial probing depths of 1-3 mm showed no alteration in probing attachment level. Pockets with baseline values of 4-6 mm showed gain of clinical attachment of 0.69 +/- 1.43 mm. The greatest gain in clinical attachment of 1.51 +/- 1.75 mm was obtained in sites with initially deep pockets of 7-9 mm. From the results of this study, it can be concluded that non surgical periodontal therapy is an effective means to reduce probing pocket depths and to improved clinical attachment levels in patients with moderate to advanced periodontitis. PMID- 1856304 TI - Assessment of ultrasonic debridement of calculus-associated periodontally involved root surfaces by the limulus amoebocyte lysate assay. An in vitro study. AB - This investigation assessed the effectiveness of an in vitro ultrasonic debridement regime on periodontally involved teeth with visually-detectable calculus deposits, using the LAL assay for lipopolysaccharides (LPS) as a marker of bacterial products. 34 single rooted teeth with extensive amounts of calcified accretions were selected, of which 10 served as uninstrumented controls for the estimation of existing LPS levels. The periodontally involved roots of the 24 experimental teeth were debrided with a Cavitron TF-10 tip for a limited time using light pressure and overlapping strokes which ensured complete surface instrumentation without reference to the presence of calculus. Marked reductions in root surface area coverage by calculus were nevertheless achieved as assessed planimetrically from photographic records of the teeth before and after debridement. The root surfaces of each tooth were then stripped away and the harvested material subjected to 'Westphal' extraction and LAL assay for LPS. The resulting LPS yields from the experimental teeth ranged from less than 0.08 to 22.387 ng compared to 1,900 to 29,200 ng from the uninstrumented controls. The extremely small residual LPS yields from the experimental teeth not only confirm the efficacy of ultrasonic debridement but, when coupled with the lack of a relationship with the widely varying amounts of the remaining calculus, support the contention that bacterial plaque rather than calculus has the greater pathogenic potential. These results reinforce the growing impression of the superficial location of bacterial toxic products associated with periodontally involved root surfaces. PMID- 1856305 TI - Comparison of the antimicrobial effect of the application of chlorhexidine gel, amine fluoride gel and stannous fluoride gel in debrided periodontal pockets. AB - The clinical and microbiological effect of locally-applied chlorhexidine gel 2%, amine fluoride gel 1.25%, stannous fluoride gel 4% or placebo gel in 40 periodontal pockets of 10 patients were studied. The gels were applied 3 x within 10 min. after mechanical debridement of the pockets. The treatment effect on the subgingival microflora was evaluated by microscopic and culture studies of the subgingival plaque samples. In addition, supragingival plaque, bleeding after probing and probing pocket depth were scored. Examination were carried out before and during a period of 36 weeks after treatment. At the start, the cultured microflora consisted mainly of anaerobic Gram-positive bacteria. Following treatment, the clinical parameters were significantly reduced. Concomitantly, the %s of spirochetes, motile rods and non-motile rods decreased significantly. A significant decrease was also found in the total anaerobic count, whereas the facultative counts remained at the same level found before treatment. This suggested that the treatment resulted in a mainly facultative subgingival microflora. The % Gram-negative rods showed a significant reduction after treatment, but returned to base line at week 12. Statistical analysis of the bacteriological and clinical examinations failed to demonstrate any significant differences between the 4 treatment groups. Thus, in comparison to the placebo gel, subgingival application of chlorhexidine gel 2%, amine fluoride gel 1.25% or stannous fluoride gel 4% did not augment the effect of mechanical debridement on bacteriological and clinical parameters during the experimental period of 36 weeks. However the indicated treatments resulted in a facultative subgingival microflora which is compatible with the host. PMID- 1856306 TI - Bleeding on probing as it relates to probing pressure and gingival health. AB - The present study was designed to determine the threshold pressure value to be applied in provoking bleeding on probing (BOP) in clinically healthy gingival units. 12 female dental hygiene students volunteered for the study. They were selected on the basis of excellent oral hygiene standards, absence of probing depths greater than 3 mm and absence of caries or dental restorations on smooth and proximal tooth surfaces. Applying a probing force of 0.25, 0.5, 0.75 and 1.0 N in one of the 4 jaw quadrants, respectively, on 2 different occasions with an interval of 10 days, bleeding on probing was assessed. Oral hygiene and gingival conditions were determined using the criteria of the plaque control record and the gingival index. On the basis of the BOP values, obtained using the lowest probing force (0.25 N), the subjects were divided into 2 groups: group 1 ("minimal BOP" value) consisted of 6 subjects yielding practically no bleeding (mean BOP = 0.9%) at both examinations, while the subjects of group 2 ("low BOP" value) had slightly higher BOP% (mean BOP = 13.4%). Both groups showed significant increase in mean BOP% with increasing probing force (0.9%-36.1% in group 1 and 13.4%-47.0% in group 2). Regression analysis revealed an almost linear correlation and a high correlation coefficient between BOP% and probing force. The comparison of the regression lines of the 2 groups showed almost identical slope inclination. However, slight differences in slope inclination were found for different sites: approximal sites clearly yielded steeper regression lines than buccal/oral sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856308 TI - The use of an oxidising mouthwash to reduce staining associated with chlorhexidine. Studies in vitro and in vivo. AB - Discolouration of the teeth, tongue and dental restorative materials associated with the use of cationic antiseptics is still the limiting factor in long-term usage of antiplaque agents such as chlorhexidine. Oxidising agents have been used successfully to remove dental stain in animals, but products and regimens have not been evaluated in humans. These pilot studies in vitro and in vivo assessed a long-established oxidising mouthwash, based on peroxyborate, for stain removal from teeth and acrylic. The laboratory studies measured chlorhexidine tea stain removal from tooth and acrylic specimens. The oxidising agent markedly reduced staining on specimens. In a short-term clinical experiment, dental staining was forced over a 2 1/2-day period by reciprocal chlorhexidine and tea rinsing. 5 rinses with the oxidising mouthwash during the next 1 1/2 days dramatically reduced staining compared with water after rinses. Additionally, a single rinse with peroxyborate following the 5 water after rinses, again considerably reduced the residual staining. Effects on tongue staining were less impressive. Both experimental models produced findings consistent with those from the animal model. The results suggest proprietary oxidising mouthwashes could have a place in the control of dental stain associated with the use of chlorhexidine. Further studies to evaluate such products in a more conventional chlorhexidine regimen are indicated. PMID- 1856307 TI - Altered tissue metabolism of progesterone in pregnancy gingivitis and granuloma. AB - The metabolism of progesterone may play a special role in the gingival physiology. The lower the metabolism the higher its hormonal activity in the tissue. In healthy human gingiva, progesterone is metabolized only partially and is therefore in an active form. In the present study, gingival samples from pregnancy gingivitis (n = 1) and granulomas (n = 4) were studied histologically and biochemically. All samples were homogenized and then incubated with [4-14C] progesterone and NADPH for 2 h at pH 7.4 and 37 degrees C. The metabolites were separated and characterized with column, solvent and thin-layer chromatographies as well as radioautography and quantified with liquid scintillation counting. The results showed low metabolism of progesterone, indicating active hormonal function as in healthy gingiva. It is suggested that progesterone functions as an immunosuppressant in the gingival tissues of pregnant women, preventing the rapid acute-type of inflammatory reaction against plaque, but allowing an increased chronic-type of tissue reaction, resulting clinically in an exaggerated appearance of inflammation. PMID- 1856309 TI - Factors associated with success among southern Cheyenne and Arapaho Indians. AB - Researchers in applied social science are seeking ways of approaching the facilitation of community-based development at the grass-roots level. Much research to date has focused on negative social aspects in communities, such as substance abuse and high numbers of school drop-outs. An innovative approach was developed that involved looking instead at successful individuals in communities. Individuals identified as successful were interviewed about the factors they associated with their own success. The experience of supportive parenting during their childhoods and moderation in alcohol and other substance use as adults were strongly correlated with success in life. The interview process provided an effective springboard for discussions and the development of intervention strategies at the community level. PMID- 1856310 TI - Limited impact of testicular self-examination promotion. AB - Analysis of data obtained through a survey of 415 men in New Orleans, Louisiana, and Rochester, New York, indicates that the transfer of testicular self examination (TSE) skills from the medical community to the public has been relatively ineffective. Only two of every 100 respondents reported monthly self examination performed at the correct time and with the proper method. The findings suggest that, until the transfer of self-detection skills is improved, one cannot assess the efficacy of the technology itself. Problems impeding such improvement are reviewed. PMID- 1856311 TI - Communicating to an alarmed community about cancer clusters: a fifty state survey. AB - A survey of all 50 U.S. states conducted in 1989 showed that 1,300-1,650 requests for cancer cluster investigations were received by state health departments. Most states responded with a three-stage process aimed at prioritizing clusters at each stage. Those situations deemed most serious were passed on to the next stage of evaluation. Thirty-eight of the 50 states said that communicating risk information to informants was a productive outcome, and 26 states sent materials to informants explaining the causes of cancer, clusters, how clusters are investigated, and other health education materials. Many states requested detailed information about reported clusters from informants. States with a major commitment to protecting public health and environment were more likely to provide information than states with weaker programs. Some officials discouraged people from pursuing their requests by trying to convince informants that a problem did not exist and by overwhelming them with questions and information. We recommend that health departments train their respondents in risk communications and establish an organizational climate that provides financial resources and institutional support appropriate to the complex task of communicating risk information to a public alarmed about a cancer cluster. PMID- 1856312 TI - Perceptions of community leaders and the merger of rural health services. AB - The merger of rural primary care and home health services offers the potential of increasing the administrative efficiency of health care, and thereby enhancing quality of care and increasing access to services, particularly health promotion. In a merger of rural health services in Northeastern Vermont, a survey of key community leaders revealed that improved organization of services, improved health status and greater accessibility of services were benefits expected and to some extent realized as a result of the merger process. The desire to preserve community-based services and having a common philosophy were important factors which served to initiate the merger. The actions of a few key individuals and the support of involved organizations were instrumental in continuing the process. PMID- 1856313 TI - Health care utilization and costs for injury in a corporate setting. AB - This article presents the incidence and costs for non-work-related injuries among 15,408 employees and their families based on health insurance claims data analysis. The treatment of injuries accounted for 11.3% of the plan's total health care costs ($31 million) for the 1986 policy year. For adults, women had a higher incidence rate than men; but for children, males had a higher incidence rate than females. A disproportionately high share of claims and charges for adults were attributed to low back disorders. Hospital admissions, length of stay and hospital days per 1,000 persons were similar for males and females, but much higher for adults than for children. This article provides an example of the utility of health insurance claims data as a source of morbidity information for disease surveillance and epidemiologic research. The analysis of claims data can be seen as a prerequisite to the development of preventive programs aimed at reducing injury rates and health care costs for injuries in a corporate setting. PMID- 1856314 TI - Enkephalin immunoreactivity and messenger RNA in a discrete projection from the nucleus of the solitary tract to the nucleus ambiguous in the rat. AB - Previous work described in the rat a circumscribed, partly somatostatinergic, interneuronal projection from the esophageal afferent part of the nucleus of the solitary tract (NTSc) to esophageal motor neurons in the compact formation of the nucleus ambiguous (NAcf: Cunningham and Sawchenko, J Neurosci 9:1668, 1989). In the present study, axonal transport, immunohistochemical and in situ hybridization histochemical techniques were used to determine whether enkephalin (ENK), a peptide known to be expressed in a number of somatostatin-containing medullary cell groups, is also expressed in the projection from the NTSc to the NAcf. The results may be summarized as follows: 1) cells immunoreactive (IR) for prepro-enkephalin (ppENK)-derived peptides were found in the NTSc in colchicine pretreated animals; in untreated animals, a dense ENK-IR terminal field was observed in the NAcf: sections stained with antisera against dynorphin-related peptides showed sparse staining in both regions; 2) signal indicating the presence of ppENK messenger RNA (mRNA) was found over the NTSc, including over a majority of cells identified using a retrograde tracing technique as projecting to the region of the NAcf; the signal for ppENK mRNA signal was greater than that for prepro-somatostatin (ppSS) in the NTSc; 3) a combined anterograde tracing immunohistochemical technique demonstrated a strong correspondence between the distribution of inputs from the NTS to the NAcf, and the distribution of endogenous ENK-IR varicosities; in addition, leucine (L)-ENK-IR was found in an appreciable number of varicosities in the NAcf that had been anterogradely labeled from the NTSc; 4) unilateral electrolytic lesions of the rostromedial NTS, which included the central subnucleus, virtually eliminated ENK-IR in the ipsilateral NAcf, while staining on the contralateral side was unaffected. Taken together, these studies provide evidence that ppENK- and ppSS-derived peptides are expressed in the pathway from the NTSc to the NAcf, a pathway thought to play a role in the reflex control of esophageal peristalsis. PMID- 1856315 TI - Origin and distribution of neuropeptide-FF-like immunoreactivity in the spinal cord of rats. AB - Neuropeptide FF, or F8Famide (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2; "morphine modulating peptide"), isolated from bovine brain, is an FMRF-NH2-like peptide with morphine-modulating effects. Neuropeptide FF (NFF) is highly concentrated in spinal cords of various mammalian species. There is evidence that NFF participates in the modulation of nociceptive mechanisms. The present study was aimed at describing the distribution and origin of the neuropeptide-FF-like immunoreactivity (LI) in the rat spinal cord. For distribution studies spinal cord sections from colchicine-treated animals were processed according to the indirect immunofluorescence method. Retrograde fluorescent tracer was injected in the lumbar dorsal spinal cord to study descending NFF-LI-containing spinal pathways. NFF-immunoreactive (ir) cell bodies were detected in the substantia gelatinosa, marginal zone, laminae III, IV, and X at all levels of the spinal cord, and the dorsolateral funiculus, and dorsal gray commissure of the lumbosacral transition zone. NFF-ir fibers and terminals were identified in laminae I-IV and X, dorsolateral funiculus, intermediolateral cell column, dorsal gray commissure, sacral parasympathetic nucleus, and ventral horn. A spinal NFF LI-containing descending pathway originating in the lamina X neurons was observed, but a supraspinal origin of descending NFF-ir fibers was not identified. According to this study the NFF-LI of the spinal cord is of intrinsic spinal origin. The anatomical distribution supports the concept that the NFF-like peptides have a role in the nociception. They may also be involved in sensory visceral reflex arcs. PMID- 1856316 TI - Descending projections to the rat sacrocaudal spinal cord. AB - Descending supraspinal and propriospinal neurons projecting to the female rat sacrocaudal spinal cord, the portion of the spinal cord that innervates the tail, were identified following injection of Fluoro-Gold into the S1-Ca2 spinal cord segments. This study attempted to determine anatomical substrates for propriospinal and supraspinal control of the tail. Propriospinal neurons were identified throughout laminae V-VIII and X at all levels of the spinal cord. The greatest density of labeling was in the lumbar enlargement, followed by the cervical enlargement, with least in the thoracic spinal cord. Within a given cord level, labeling was greatest within the intermediate zone. In addition, other prominent spinal cord collections included neurons in 1) lamina V of the lumbar enlargement, 2) dorsal lamina X of the cervical enlargement, and 3) the lateral spinal nucleus within the cervical enlargement. Supraspinal cells were identified within raphe nuclei, reticular formation nuclei, dorsal column nuclei, vestibular nuclei, noradrenergic groups, the red nucleus, the periaqueductal gray, the hypothalamus, and the motor cortex. These data indicate that there are significant descending projections to the sacrocaudal spinal cord, with distributions similar to those of other cord levels. Functionally, important supraspinal and propriospinal influences on tail, pelvic viscera and limbs, such as with locomotion, balance, defense, micturition, defecation, and sexual functions, may be mediated by these connections. PMID- 1856317 TI - Evidence for the presence, synthesis, immunoreactivity, and uptake of GABA in the nervous system of the snail Helisoma trivolvis. AB - In the present study several techniques were employed to test the hypothesis that gamma-aminobutyric acid (GABA) is a neurotransmitter in the central nervous system (CNS) of the pond snail Helisoma trivolvis (Mollusca, Pulmonata). First, by using chromatographic techniques, the presence of GABA and its differential distribution among the ganglia constituting the CNS was demonstrated. Second, de novo synthesis of 3H-GABA from 3H-glutamate was shown by the CNS. Levels of both endogenous and newly synthesized GABA were greatest in the buccal, cerebral, and pedal ganglia. Third, indirect immunohistochemistry of wholemounts revealed a central network of GABA-like immunoreactive neurons. With the possible exceptions of two pairs of fibers in nerve trunks, all projections from GABA-immunoreactive neurons were confined to the CNS, suggesting a predominantly central role for GABA. Stained neurons were found on the dorsal surface of the buccal ganglia and throughout the cerebral and pedal ganglia. No GABA-immunoreactive cell bodies were observed in the parietal, pleural, or visceral ganglia. Finally, uptake of 3H-GABA was examined autoradiographically in sectioned ganglia. A pattern of radiolabelled cells was observed that closely resembled the distribution of GABA immunoreactive neurons. The data described above fulfill several criteria necessary to establish GABA as a transmitter in the nervous system of Helisoma. Taken together with previously obtained pharmacological evidence demonstrating that GABA acts on Helisoma central neurons, GABA is considered to be a strong candidate for a neurotransmitter in Helisoma. PMID- 1856318 TI - Birthdates of trigeminal ganglion cells contributing axons to the infraorbital nerve and specific vibrissal follicles in the rat. AB - Prenatal labelling with [3H]-thymidine was combined with retrograde tracing techniques in adult rats to determine the birthdates of the trigeminal (V) ganglion cells that contributed axons to the infraorbital nerve (ION) and the generation of the subsets of ION cells that innervated specific vibrissae follicles (C-1 and C-5). The V ganglion cells contributing axons to the ION are born between embryonic (E-, E-0 = the day of conception) days 9.5 and 14.5. The percentages (normalized so that they total 100%) of the total V ganglion population born on E-9.5 through E-14.5 were 5.8, 25.7, 19.8, 23.4, 21.0, and 4.4%, respectively. The distribution of birthdates for the V ganglion cells that were retrogradely labelled from the ION closely matched that for the ganglion as a whole. All of these neurons were also born on E-9.5 through E-14.5, and the percentages born on each day were 6.3, 23.6, 18.1, 24.0, 23.6, and 4.4%. Finally, a similar distribution of birthdates was obtained for the V ganglion cells that were retrogradely labelled after injection of retrograde tracers into either the C-1 or C-5 vibrissae follicles. We were unable to detect any distinctive spatial distributions for either all V ganglion or ION cells born on a specific embryonic day. Furthermore, neurons with a given birthdate and that innervated a given follicle were distributed throughout the entire region containing all of the ganglion cells supplying the follicle in question. Therefore, it appears that the V ganglion cells contributing axons to the ION are born over the entire period of ganglion neurogenesis and further that the organization of the ION's innervation of the periphery is not a function of cell birthdate. PMID- 1856319 TI - Gonadotropin hormone-releasing hormone (GnRH) immunoreactivity in the mesencephalon of sharks and rays. AB - Other than association with the terminal nerve (TN), little is known concerning the distribution of gonadotropin hormone-releasing hormone (GnRH) in elasmobranchs. The purpose of this study was to identify GnRH immunoreactivity in the brains of three elasmobranch species with special regard to the mesencephalon. The round stingray (Urolophus halleri), thornback guitarfish (Platyrhinoidis triseriata), and leopard shark (Triakis semifasciatus) were used and immunocytochemistry was performed with antisera to both salmon and mammalian GnRH. A large GnRH-immunoreactive (ir) nucleus extends rostrocaudally for approximately 1.5 mm along and adjacent to the midline of the midbrain near the area of the oculomotor nerve. GnRH-ir fibers surround the nucleus and are found diffusely throughout the mesencephalon; some of the fibers may contact the ventricle. The medulla and spinal cord contain ir fibers that most likely originate from the midbrain nucleus. Mesencephalic GnRH-ir cell groups have been reported in representatives of all vertebrate classes with the exception of agnathans and mammals. Such a well-developed cell group in elasmobranchs may aid in understanding the evolution of GnRH systems with regard to the mesencephalon as well as providing insight to the functional significance of this cell group. Possible homologies to mesencephalic GnRH systems reported in other vertebrates is discussed as well. PMID- 1856320 TI - Mitral cell-to-glomerulus connectivity: an HRP study of the orientation of mitral cell apical dendrites. AB - It has been suggested that the principal output cells of the main olfactory bulb, the mitral cells, along with the glomerulus they enter, form an anatomical and functional column. To test the extent to which mitral cell somata lying close together in the mitral cell layer are connected to the same glomerulus, we reconstructed 267 mitral cells labeled by extracellular injections of horseradish peroxidase (HRP) in the external plexiform layer. Results show that apical dendrites tilt rostrally from the somata to the glomeruli and this tilt is gradually greater as the somata are located more and more rostrally in the olfactory bulb. The apical dendrites of most mitral cells in the same region of the bulb are parallel. We analyzed the degree to which dendrites were parallel by measuring the difference in angle of all pairs of apical dendrites in each section, with the restriction that no cells were separated by more than 500 microns. About half of these pairs of dendrites differed in angle by 20 degrees or less and were therefore said to be parallel. The degree of parallelism did not vary with the cell pair location or with intercell distance. Study of glomerular connections of pairs of mitral cells as a function of intercell distance revealed that 96% of mitral cells connected to the same glomerulus were separated by less than 120 microns, while 72% of cells connected to adjacent glomeruli and only 29% of cells connected to distant, i.e., nonadjacent, glomeruli were separated by less than 120 microns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856321 TI - Lateral asymmetries and testosterone-induced changes in the gross morphology of the hypoglossal nucleus in adult canaries. AB - The caudal portion of the hypoglossal nucleus (tracheosyringeal, nXIIts) contains the motor neurons that innervate the syrinx in songbirds. It receives projections from telencephalic and midbrain nuclei that are necessary for song production. Its neurons concentrate androgens. The present study assesses the gross morphology of the hypoglossal nucleus in canaries. In this species song is more frequent, elaborate, and stereotyped in males than in females. Adult females respond to testosterone by developing a stereotyped song that is sung frequently. Song in male canaries is much more disrupted by damage on the left side of the song system than by damage on the right. We find anatomical correlates for each of these attributes in the nXIIts. This nucleus is 83% larger in males than in females. This is caused primarily by a sex difference in neuropil volume as there is no significant sex difference in the number of neurons in nXIIts. nXIIts grows by 34% in females given testosterone as adults. It is about 8% larger on the left than on the right in males, females, and females treated with testosterone. Sex differences are also found in the rostral (lingualis) portion of nXII, which controls muscles of the tongue, but there is no effect here of adult treatment with testosterone. Comparisons of these data with earlier measures of synaptic density and morphology in nXIIts suggest that the testosterone acts on this nucleus by inducing a modest increase in synapse numbers and by altering the efficacy of synapses in nXIIts. This contrasts with the effects of testosterone on n. robustus archistriatalis, a telencephalic component of the song system in which testosterone induces massive amounts of synaptogenesis. PMID- 1856322 TI - Embryonic development of choline acetyltransferase in thoracic spinal motor neurons: somatic and autonomic neurons may be derived from a common cellular group. AB - This investigation focused on the relationship between neurotransmitter phenotype expression and rat motor neuron development, as studied with choline acetyltransferase (ChAT) immunocytochemical techniques. The development of two subclasses of motor neurons, somatic and autonomic efferents, was examined in the upper thoracic spinal cord. ChAT was first detected in a few neurons on embryonic day 12 1/2 (E12 1/2), and in numerous cells located in a single, ventrolaterally located column in the intermediate zone on E13. By E14, this group of ChAT positive neurons was more intensely immunoreactive, and their axons could be traced to appropriate targets in developing somatic muscle and paravertebral sympathetic ganglia. During the E15-16 period, somatic and autonomic motor neurons separated into two distinct subgroups, with the latter cells being observed to translocate dorsally. By E17, these autonomic motor neurons reached their final positions in the midportion of the intermediate zone. The autonomic motor neurons were observed to extend transverse dendritic bundles across the spinal cord between E15-16, but evidence of the longitudinal bundles of sympathetic preganglionic dendrites was not observed until after birth. A recent study of cholinergic thoracic motor neurons found that both somatic and autonomic cells were generated synchronously during the E11-12 period (Barber et al., Soc Neurosci Abstr 15:588, 1989). In combination with the present results, these data indicate that no more than 1 1/2 days are necessary after motor neuron genesis before a few cells begin to express detectable levels of ChAT, and that no more than 2 days are required before large numbers express this marker of the cholinergic phenotype. Further comparisons of the present findings with those of previous investigations of the development of both somatic and autonomic motor neurons (Dennis et al., Dev Biol 81:266, 1981; Rubin, J Neurosci 5:685, 697, 1985) indicate that these cells contain ChAT at the time their axons are growing toward their respective peripheral targets 1 day before the time when physiological evidence of function is manifest. Furthermore, the present results suggest that both subclasses of motor neurons initially migrate together from the ventricular zone into a single motor column within the ventral intermediate zone, and that the autonomic neurons subsequently translocate dorsally. Thus, autonomic motor neurons appear to be an exception to the generalization that postmitotic neurons migrate directly from the germinal zone to their final positions within the central nervous system. PMID- 1856323 TI - Formation of ganglia in the gut of the chick embryo. AB - We have examined the formation of myenteric ganglia in the developing avian enteric nervous system. The monoclonal antibody HNK-1 was used to identify neural crest-derived cells in whole mounts of fore- and midgut of chick embryos. We find that the crest-derived cells extend processes to their neighbors and form a complex network in the wall of the gut. Formation of this network is an unusual behavior of crest-derived cells and suggests the gut microenvironment is critical to this behavior. This cellular network disappears after ablation of the vagal neural crest, indicating the HNK-1-stained cellular network arises from crest derived cells. The network is found in the gut wall before the vagal nerve fibers are present. This network is first found in the primordium of the proventriculus, distal to the evagination of the lung buds, and progresses just proximal to the yolk stalk at embryonic day (E) 3.5 and almost to the ileocecal junction at E5.5. The number of cells and the complexity of the network decrease in a rostral caudal direction down the length of the gut at these stages. The leading edge of the network consists of cells serially arranged in longitudinally running strands. The organization of the network changes with increasing embryonic age; we have focused on network changes in the proventriculus. In the primordium of the proventriculus at E3.5, the network consists of a cluster of one or two adjacent crest-derived cells, which extend processes to a number of neighboring crest-derived cells. At E5.5 large increases in the number of cells per cluster and in the length of cellular connectives between clusters are apparent. At E6.5 a crude meshwork of clusters is seen. At E10.5 the arrangement of cell clusters resembles the pattern of ganglia found in the adult myenteric plexus. This network may provide the environmental cues for the differentiation of enteric neurons and a framework for the pattern of ganglia found in the adult enteric nervous system. PMID- 1856324 TI - Further evidence of extrinsic forces in bending of the neural plate. AB - Bending of the neural plate has long been considered to be driven by principally intrinsic forces generated by wedging of neurepithelial cells. Our previous studies have shown that during neural fold elevation, significant neurepithelial cell wedging occurs only within the median hinge point (MHP), the midline region of neural plate anchored to the notochord. We have also shown that neural fold elevation can still occur when MHP cells are prevented from becoming wedge-shaped but fails to occur when the neural plate is separated from lateral nonneurepithelial tissues, even though MHP cells still become wedge-shaped and the midline neural plate still furrows. Together, these results suggest that neural fold elevation, rather than being driven by neurepithelial cell wedging, is driven, at least in part, by extrinsic forces generated by lateral nonneurepithelial tissues. However, it could be argued that in the absence of localized neurepithelial cell wedging, compensatory and atypical cell wedging occurred uniformly throughout the neural plate, providing forces adequate for neural fold elevation. Likewise, it could be argued that in the process of separating the neural plate from lateral nonneurepithelial tissues, the neural plate was damaged to the extent that the neural folds were unable to elevate. To investigate the validity of these arguments, we removed the following tissues microsurgically prior to neural fold elevation: MHP cells, varying amounts of lateral neurepithelial cells (L cells), and the tissues directly underlying these two populations of neurepithelial cells. We found that the neural folds still formed and underwent elevation, convergence, and fusion, resulting in an essentially normal neural tube, even though MHP cells, the underlying notochord, and some L cells were absent for long craniocaudal distances. These results demonstrate that microsurgery alone does not damage the neural plate sufficiently to prevent neural fold elevation, convergence, and fusion. Moreover, the fact that each of the two persisting remnants of lateral neurepithelium generally remained straight and consistently changed their orientation from horizontal to vertical rather than curling suggests very strongly that bending of the neural plate in these embryos is not the result of compensatory and atypical cell wedging. Finally, the results provide further direct evidence of extrinsic forces in bending because the two remnants of lateral neurepithelium, which were oriented horizontally at the time of tissue extirpation, could not have become oriented vertically in the absence of such forces. PMID- 1856325 TI - Morphology and frequency of axon terminals on the somata, proximal dendrites, and distal dendrites of dorsal neck motoneurons in the cat. AB - The purpose of the present study was to compare the frequency of different classes of axon terminals on selected regions of the somatodendritic surface of dorsal neck motoneurons. Single motoneurons supplying neck extensor muscles were antidromically identified and intracellularly stained with horseradish peroxidase. By using light microscopic reconstructions as a guide, axon terminals on the somata, proximal dendrites (within 250 microns of the soma), and distal dendrites (more than 540 microns from the soma) were examined at the electron microscopic level. Axon terminals were divided into several classes based on the shape, density, and distribution of their synaptic vesicles. The proportion of axon terminals belonging to each axon terminal class was similar on the somata and proximal dendrites. However, there were major shifts in the relative frequency of most classes of axon terminals on the distal dendrites. The most common classes of axon terminals on the somata and proximal dendrites contained clumps of either spherical or pleomorphic vesicles. These types of axon terminals accounted for more than 60% of the axon terminals on these regions. In contrast, only 11% of the axon terminals found on distal dendrites belonged to these types of axon terminals. The most commonly encountered axon terminal on distal dendrites contained a dense collection of uniformly distributed spherical vesicles. These types of axon terminals accounted for 40% of all terminals on the distal dendrites, but only 5-7% of the axon terminals on the somata and proximal dendrites. Total synaptic density on each of the three regions examined was similar. However, the percentage of membrane in contract with axon terminals was approximately four times smaller on distal dendrites than somata or proximal dendrites. Axon terminals (regardless of type) were usually larger on somata and proximal dendrites than distal dendrites. These results indicate that there are major differences in the types and arrangement of axon terminals on the proximal and distal regions of dorsal neck motoneurons and suggest that afferents from different sources may preferentially contact proximal or distal regions of the dendritic trees of these cells. PMID- 1856326 TI - Estrogen influences on oxytocin mRNA expression in preoptic and anterior hypothalamic regions studied by in situ hybridization. AB - Possible estrogen influences on oxytocin mRNA expression were studied in preoptic and anterior hypothalamic regions as might be important for behavioral as well as neuroendocrine controls. In situ hybridization for oxytocin mRNA determination was supported by immunocytochemical identification and was compared with vasopressin mRNA in situ hybridization. With these techniques, oxytocin expressing neurons were identified in medial preoptic, anterior commissural, periventricular, paraventricular, supraoptic, and perifornical nuclei as well as the bed nucleus of the stria terminalis and intersupraopticoparaventricular (internuclear) islands. Distribution and number of oxytocin mRNA-containing neurons and oxytocin mRNA levels were compared between ovariectomized control rats given cholesterol implants and ovariectomized rats given short-term (2 days) or long-term (2 months) estradiol treatment (10% estradiol, subcutaneous silastic implants). Effectiveness of long-term estrogen treatment was confirmed behaviorally. While there was a trend in several cell groups for a larger number of oxytocin-mRNA-containing neurons to be observed following 2 days of estrogen treatment, this was not statistically significant. Moreover, additional oxytocin mRNA containing cell groups were not seen after short or long estradiol treatment. With computer-aided analysis, mean pixels per oxytocin-mRNA expressing neuron (reflecting oxytocin mRNA content) were compared between groups: In the supraoptic nucleus and the anterior commissural nucleus, these were increased both by 2 days and 2 months of estradiol treatment. These differences may be important in modulating female reproductive behavior. Present findings also suggest that estradiol can affect the oxytocinergic system via an indirect route since the cell groups influenced here by estradiol do not contain estrogen receptors. Oxytocinergic neurons may serve as a good system to compare direct transcriptional with indirect effects of hormones. PMID- 1856327 TI - Quantitative study of the tectally projecting retinal ganglion cells in the adult frog. II. Cell survival and functional recovery after optic nerve transection. AB - It is known from previous work that ganglion cells disappear from the retina in significant numbers during optic nerve regeneration in the adult frog. In the present study, the population size of surviving ganglion cells that have returned axon terminals to the correct tectal loci was estimated by counts of retrogradely labeled cells in retina-flat-mounts after tectal injections of HRP. Bilaterally symmetric injections were delivered to allow comparison of the normal and affected retinas. The frogs studied had regenerated the left optic nerve and had visually guided behaviors initiated by the recovered eye (see below). The proportion of tectally projecting ganglion cells in the normal retinas and in retinas of normal frogs studied in parallel ranged from 83-86% (Singman and Scalia: J. Comp. Neurol. 302:792-809, 1991). In the affected retinas, the subpopulation of tectally projecting cells was reduced by 40-90% after regeneration, and the relative size of this subpopulation ranged from 67-86%. The optic tectum was injected unilaterally in one specimen, on the side ipsilateral to the regenerated (left) optic nerve. The HRP-labeled ganglion cells in the ipsilateral (left) retina accounted for only 0.8% of the surviving ganglion cells in this animal, whereas it was previously found that the ipsilateral tectally projecting ganglion cells normally amount to 0.9-2.3% (Singman and Scalia, op. cit.) In frogs recovering from transection of the left optic nerve, the frequency, latency, and accuracy of the prey-acquisition responses initiated by the recovering eye were compared with those initiated by the normal eye. Mealworms or lure dummies were used to stimulate prey acquisition. In one experiment, the stimuli were presented unilaterally in the monocular fields of frogs permitted to use both eyes. Prior to the fourteenth postoperative week, the affected eye initiated responses of abnormally long latency and low frequency. In contrast, responses initiated by the affected eye after 14 weeks appeared to be normal in all respects. In another experiment, the normal eye was sutured shut in some frogs recovering for at least 24 weeks and then the affected eye was retested. The affected eye was capable of consistently initiating brisk and accurate prey acquisition. In a final experiment, two stimuli were presented simultaneously in bilaterally symmetric regions of the monocular fields of frogs surviving at least 42 weeks. These fully recovered frogs showed no preference for using either the normal or the recovered eye. Despite severe loss of tectally projecting ganglion cells during optic nerve regeneration, frogs are capable of apparently normal visual responses in prey acquisition tests. PMID- 1856328 TI - Direct observations of synapses between GABA-immunoreactive boutons and identified spinocervical tract neurons in the cat's spinal cord. AB - Three spinocervical tract neurons in adult cats were physiologically characterized and intracellularly labelled with horseradish peroxidase. The neurons were reconstructed and examined with the light microscope and were prepared for postembedding immunochemical analysis by using an antiserum which specifically recognizes GABA in glutaraldehyde-fixed tissue. Semithin sections were tested and examined with the light microscope. Somata, proximal, and distal dendrites of all three cells were associated with numerous punctate GABA immunoreactive structures. Immunoreactive perikarya of small neurons in the vicinity of spinocervical tract cells were also observed. Ultrastructural analysis, with the immunogold technique, revealed that somata and proximal dendrites of all three neurons received synaptic contacts (about 37% of total synapses) from GABA-immunoreactive boutons and that distal dendrites were also associated with substantial numbers of immunoreactive structures (about 27% of synapses). Immunoreactive boutons were small (about 1 micron in diameter), contained irregularly shaped agranular vesicles, and formed symmetrical synaptic junctions with identified neurons. An additional group of immunoreactive boutons was observed to be associated with one of the cells only; these contained many large dense-core vesicles in addition to small agranular vesicles. Boutons containing round agranular vesicles and flattened agranular vesicles were not observed to be immunoreactive. The evidence supports the idea that much of the postsynaptic inhibition observed in spinocervical tract neurons is mediated by GABA and that even the most distal dendrites of these neurons receive inhibitory inputs. PMID- 1856329 TI - Relationship of retinotopic ordering of axons in the optic pathway to the formation of visual maps in central targets. AB - We examined in rats the relationship between the ordering of retinal axons in the optic pathway and the formation of a retinotopically organized projection to their primary target, the contralateral superior colliculus (SC). We have previously found that axons labeled by focal injections of 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) made in temporal or nasal retina of perinatal rats commonly mistarget along the medial-lateral and rostral caudal axes of the SC. By postnatal day (P) 11-12, the retinocollicular projection attains an adult-like topography. Incorrectly targeted axons or axon segments are removed; axons that persist terminate in the topographically appropriate part of the SC (Simon and O'Leary: Dev Biol 137:125, 1990). In the present study, we made similar DiI injections, covering less than 2% of the retinal area, in peripheral temporal, nasal, superior, or inferior retina, in rats of two age groups, embryonic day (E) 21 to P (postnatal day) 2 and P11-P17. Whole mounts of retina, optic nerve and tract, and SC, and cross sections of the optic nerve, were examined. In E21-P2 rats, retinal axons labeled from each retinal site are diffusely distributed in the SC, and poorly ordered in the optic pathway. In retina, labeled axons travel in fascicles directly from the injection site to the optic disc, but neighbor relationships begin to degrade as fascicles split and mix. Retinotopic order is virtually lost in the optic nerve; axons labeled from each injection site disperse throughout its cross-sectional area, but the labeled axons tend to be concentrated toward a specific half of the nerve depending upon their retinal origin. This slight tendency toward retinotopic order increases in the optic tract, but axons are still poorly ordered as they leave the tract and enter the SC. Targeting errors along the medial-lateral axis of the SC, but apparently not along its rostral-caudal axis, are related to the positioning of axons across the width of the optic tract. In P11-P17 rats, axons labeled from each injection site arborize only in a small, topographically correct part of the SC. However, the distributions of labeled retinal axons observed in whole mounts of the retina and optic pathway have a degree of disorder similar to those in E21-P2 rats. Further, the scatter of labeled axons in optic nerve cross sections is comparable in both age groups. Therefore, the emergence of topographic order in the retinocollicular projection is not accompanied by an emergence of a retinotopic ordering of axons in the optic nerve.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1856330 TI - Immunohistochemical differentiation of electrophysiologically defined neuronal populations in the region of the rat hypothalamic paraventricular nucleus. AB - Intracellular recording and labeling were combined with neurophysin immunohistochemistry to study neurons in the paraventricular nucleus region of the rat hypothalamus. Neuronal membrane properties were examined in hypothalamic slices, and cells were labeled by injecting biocytin or Lucifer yellow. Slices were then embedded, sectioned, and immunohistochemically processed for neurophysin. Immunoreactivity patterns, and in some cases counterstaining, enabled determinations of the cytoarchitectonic positions of recorded cells to be made. Recorded cells were divided into three types according to their electrophysiological characteristics. The first type lacked low-threshold Ca2+ spikes and displayed linear current-voltage relations, a short time constant, and evidence for an A current. These were relatively large cells that were typically immunoreactive for neurophysin and were situated near other neurophysin-positive neurons. The second type had relatively small low-threshold potentials that did not generate bursts of Na+ spikes. These cells had heterogeneous current-voltage relations and intermediate time constants. They did not label for neurophysin, and most were located in the parvicellular subregion of the paraventricular nucleus. The third type had large low-threshold Ca2- spikes that generated bursts of Na+ spikes, and these cells had nonlinear current-voltage relations and long time constants. These neurons were dorsal or dorsolateral to the paraventricular nucleus and were not immunoreactive for neurophysin. These results indicate that paraventricular magnocellular neurons lack low-threshold potentials, whereas paraventricular parvicellular neurons display low-threshold potentials that generate one or two action potentials. Neurons that fire spike bursts from low threshold potentials are adjacent to the paraventricular nucleus, confirming earlier reports. PMID- 1856331 TI - Disruption of developmental timing in the albino rat retina. AB - We have examined the spatial and temporal gradients of two developmental processes in albino and pigmented rats: outer plexiform layer (OPL) development, and rate of cell production. The OPL first appears as a thin, discontinuous break in the cytoblast layer that is frequently interrupted by the profiles of migrating neuro- and glioblasts. In both strains, this occurs in an area temporal to the optic disc that corresponds to the eventual site of peak ganglion cell density, but is not located along the line of nasotemporal division. The OPL is first evident at P5 in pigmented animals, but its appearance in albino animals is delayed approximately 30 hours, and its development appears to follow a flatter spatial gradient than in pigmented animals. In pigmented animals OPL formation is complete over most of the retina by P10, but in albino animals at this age it is yet to be completely formed at any retinal location. Reductions in mitotic activity are also first evident in temporal retina, but unlike OPL development, appear to follow the same temporal-spatial gradient in both strains. Reductions in temporal retina are obvious by P4, and mitotic activity has ceased altogether in midtemporal retina by P6 and throughout most remaining retinal regions by P8. Thus, the initial reduction of mitotic activity precedes the onset of OPL formation in both strains, but OPL development lags behind the reduction of mitotic activity to a greater extent in albino than in pigmented animals. Some aspects of differentiation within the inner nuclear layer (INL) were also examined. Just prior to the time of the onset of OPL formation, three distinct sublaminae are apparent in the INL. Cells in the innermost sublamina appear to be in an early stage of differentiation. Cells in the middle sublamina appear to be postmigratory, but have not yet begun to differentiate. Cells in the outermost sublamina have the appearance of migrating neuroblasts. At least some of these outer cells appear to migrate across the developing OPL to the outer nuclear layer, since the outermost sublamina becomes thinner and eventually disappears at the same time that the OPL becomes a continuous, uninterrupted plexiform layer. Cells of the middle sublamina apparently begin differentiation at about the time that this migration is complete. Although this sequence is the same in both albino and pigmented strains, its onset is delayed in albino animals by the same amount as the onset of OPL formation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1856332 TI - Active zone organization and vesicle content scale with bouton size at a vertebrate central synapse. AB - A common observation in studies of neuronal structure is that axons differ in the size of their synaptic boutons. The significance of this size variation is unclear, in part because we do not know how the size of synaptic boutons is related to their internal organization. The present study has addressed this issue by using three-dimensional reconstruction of serial thin sections to examine the ultrastructure of synaptic boutons that vary in size. Our observations are based on complete or near-complete reconstructions of 53 synaptic boutons contacting large neurons in the ventromedial gray matter of the upper cervical spinal cord (probable neck motor neurons). We characterized bouton size in terms of volume and total area of membrane apposed to the motor neuron surface (apposition area). Boutons vary in apposition area by a factor of 40, and there is a significant positive correlation between our two measures of bouton size. In addition, bouton size is systematically related to four ultrastructural variables: 1) total active zone area, 2) number of active zones, 3) individual active zone area, and 4) number of synaptic vesicles. The correlations between these variables and both of our measures of bouton size are positive and significant. These data suggest that bouton size may be an index of ultrastructural features that are thought to influence transmitter storage and release. PMID- 1856333 TI - Cell migration in the rat embryonic neocortex. AB - Three-dimensional reconstructions of the normal rat embryonic (E) neocortex on days E15, E17, E19, and E21, using Skandha (software designed by J. Prothero, University of Washington, Seattle), show that the neocortical ventricular zone shrinks rapidly in the medial direction during cortical morphogenesis. [3H]thymidine autoradiography indicates that the shrinkage of the ventricular zone occurs before neurons in lateral and ventrolateral parts of layers IV-II are generated. Consequently, most of these neurons originate 400-1000 microns medial to their settling sites in the cortical plate. Embryos killed at daily intervals up to E21 after a single injection of [3H]thymidine on either E17 or E18 revealed the presence of a prominent migratory path, the lateral cortical stream, used by neurons migrating to the lateral and ventrolateral cortical plate; neurons migrating to the dorsal cortical plate follow a direct radial path. Arrival times of neurons in the cortical plate depend on the migratory path and are proportional to the overall distance travelled. Neurons that migrate only radially arrive in the dorsal cortical plate in two days (shortest route). Neurons that migrate laterally arrive in the lateral cortical plate in 3 days (longer route) and in the ventrolateral cortical plate in 4 days (longest route). [3H]thymidine autoradiography also shows that cells generated in the neocortical ventricular zone migrate in the lateral cortical stream for 5 or more days and accumulate in a reservoir. Cells leave the reservoir to enter the piriform cortex and destinations (as yet undetermined) in the basal telencephalon. The lateral cortical stream is found wherever the neocortical primordium surrounds the basal ganglia and is absent behind the basal ganglia. A computer analysis of nuclear orientation in anterior and posterior parts of the intermediate zone in the dorsal neocortex between days E17 and E22 shows that horizontally oriented nuclei are more common anteriorly where many cells are migrating laterally than posteriorly where most cells are migrating radially. PMID- 1856335 TI - Managed care: a boon or bane in the 90's. PMID- 1856334 TI - Managed dental care--coming soon to your neighborhood. PMID- 1856336 TI - The influence of alcohol. PMID- 1856337 TI - One dentist's opinion on being average. PMID- 1856338 TI - Human gnathostomiasis. AB - Two patients became infested with Gnathostoma nipponicum after eating raw loach fish they had caught in a rice field in central Japan. A fragment of Gnathostoma was found in a biopsy from one of them. The sera of both patients reacted with Gnathostoma antigen using indirect immunofluorescence. Scanning electron microscopy was performed on blocks of the paraffin-embedded parasite sample and the viscera of a fish from the same rice field. The risk of eating raw freshwater fish is discussed. PMID- 1856339 TI - Hyalohyphomycosis masquerading as squamous cell carcinoma. AB - A case of primary cutaneous hyalohyphomycosis in a healthy individual is presented. The initial clinical impression was keratoacanthoma or squamous cell carcinoma. Upon excision, the lesion proved to be an example of cutaneous hyalohyphomycosis due to an unidentified, non-pigmented fungal organism. The lesion was completely excised, and the patient was treated with saturated solution of potassium iodide. To date, there has been no evidence of recurrence. The clinical, histologic and mycologic aspects of hyalophyphomycosis are discussed. PMID- 1856341 TI - Generalized eruptive histiocytoma: a report of a variant case showing the presence of dermal indeterminate cells. AB - We describe a 14-year-old Japanese girl with a variant of generalized eruptive histiocytoma. She presented with the characteristic features of classical generalized eruptive histiocytoma but with the following minor differences. Clinically, some of the papular eruptions tended to coalesce to form plaques. Histoligically, some of the histiocytic cells were S-100 protein- and OKT-6 positive; these were thought to be indeterminate cells because they lacked Birbeck granules. In addition, PAS-positive cells were few and there were some intermingled lymphocytes and a few eosinophils. PMID- 1856340 TI - Ultrastructural study of a mucinous carcinoid of the skin. AB - A tumor of 60 years' duration overlying the sternum of an 87-year-old woman is described. Histologically, the tumor was composed of lobules and cords of epithelial cells with finely granular, eosinophilic cytoplasm. The epithelial nests were floating in large pools of mucinous stroma, separated by thin fibrovascular septa. Cytoplasmic argyrophilia was seen by Grimelius silver stain. Positive reactions of the tumor cells were also found for chromogranin and neuron specific enolase. Ultrastructural study revealed that the cytoplasm of the tumor cells contained two types of granules: neurosecretory and mucinous. From these findings, the present tumor is considered to be a carcinoid tumor with amphicrine cells, and the term "mucinous carcinoid" of the skin seems to be appropriate for the diagnosis of the present case. PMID- 1856342 TI - Proliferating trichilemmal cyst with apocrine-acrosyringeal and sebaceous differentiation. AB - An adnexal tumor on the scalp of a 74-year-old woman is described. Histologically, the tumor was composed of cystic structures showing typical trichilemmal keratinization. The tumor cells in the cyst walls often formed duct like or squamous eddy-like structures and occasionally showed vacuolation or poroma-like change. Ultrastructurally, some tumor cells showed differentiation either toward the acrosyringium or sebaceous cells. From these findings, the present tumor is considered to differentiate toward various parts of the hair follicle including infundibulo-isthmus epithelium, apocrine acrosyringium, and sebaceous cells. PMID- 1856343 TI - A third case of cutaneous papillary squamous cell carcinoma. PMID- 1856344 TI - Sushi and the skin. PMID- 1856345 TI - The spectrum of lichenoid dermatitis. PMID- 1856346 TI - Lysozyme in abnormal dermal elastic fibers of cutaneous aging, solar elastosis and pseudoxanthoma elasticum. AB - Staining of elastic fibres with antilysozyme antibodies has been noted previously. In this study, we examined the staining pattern of dermal elastic fibres in aging, solar elastosis, and lesional skin of pseudoxanthoma elasticum (PXE) using an antibody to lysozyme and the indirect-peroxidase technique. To assess the effects of aging, sun-protected skin (buttock) from a younger and an older group of patients was used. Sun damage was studied in skin specimens from varying sun-exposed body regions (trunk; head and neck). No staining was seen in sun-protected skin from younger individuals, whereas sun-protected skin from older persons had scattered positive fibres. Solar elastotic material was intensely positive and the number of positive fibres appeared to correlate with the amount of sun damage. Abnormal elastic fibres in PXE also stained positively, but less intensely, than fibres in solar elastosis. This study shows that changes in the elastic fibres due to degenerative processes or genetic factors results in altered antigenic expression of the fibres. This may be an epiphenomenon secondary to changes in proteoglycans, which are known to occur with solar elastosis and PXE, or may represent an adaptive phenomenon to maintain the elastic properties of the altered fibres or to decrease their antigenicity. PMID- 1856347 TI - Immunohistochemical demonstration of actinically damaged elastic fibers in keratoacanthomas: an aid in diagnosis. AB - The inclusion of elastic fibers within the epithelium of keratoacanthomas is a phenomenon suggested to be an aid in differentiating this lesion from squamous cell carcinoma. Antilysozyme antibodies have recently been noted to stain actinically damaged elastic fibers but not those from sunprotected skin. In this study, 54 keratoacanthomas and 46 squamous cell carcinomas were stained with a histochemical elastic tissue stain and polyclonal antibody to lysozyme using an immunoperoxidase technique. Elastic fibers were demonstrated in keratoacanthomas (37/54, 68%) significantly more often than squamous cell carcinomas (12/46, 26%) (p less than 0.001) using both techniques. This study confirms that the inclusion of elastic fibers occurs significantly more often in keratoacanthomas than squamous cell carcinomas. These elastic fibers were also actinically damaged, suggesting a role for sun damage in the evolution of keratoacanthoma. PMID- 1856348 TI - Alopecia syphilitica, a simulator of alopecia areata: histopathology and differential diagnosis. AB - Alopecia syphilitica (AS) may be "moth-eaten" or diffuse, clinically, and be confused with alopecia areata (AA) or other alopecias. The English language literature contains scant information regarding the histopathology of AS, and the resemblance between AS and AA has not been given adequate recognition. We report the histopathological findings of AS from nine patients with secondary syphilis and acute hair loss. The alopecia was moth-eaten in four patients and diffuse, but slightly moth-eaten, in five. Microscopically, the dermoepidermal interface was not involved. The numbers of hair follicles were diminished, with increased numbers of catagens and telogens. Lymphocytic infiltration was present around the hair bulbs and fibrous tracts in eight cases. Plasma cells were present in four biopsies. Other less common findings included lymphocytes in the isthmus, parabulbal lymphoid aggregates, and granulomatous infiltrate in the upper dermis. The findings, save for the follicular changes, resembled those of macular/maculopapular syphilides outside the scalp. With the follicular changes, the overall patterns resembled AA closely. The modified Steiner stain did not reveal spirochetes in any of our cases and failed to differentiate between AS and AA. Comparing the AS cases to 13 cases of AA, we found only a few differentiating features. The presence of peribulbal eosinophils strongly suggests AA. Without peribulbal eosinophils, the presence of plasma cells, abundant lymphocytes in the isthmus, or parabulbal lymphoid aggregates suggests AS. PMID- 1856349 TI - In-vivo magnetic resonance imaging studies of mammogenesis in non-pregnant goats treated with exogenous steroids. AB - Mammogenesis and lactation were induced in five multiparous, non-pregnant goats by treatment with oestrogen and progesterone for 11 d, followed by dexamethasone for 3 d. Reserpine was administered during the last 5 d. All five goats lactated, although milk yield was less than had been achieved in previous natural lactations. Mammary development was assessed in vivo, using magnetic resonance imaging. Although parenchyma volume increased by more than 6-fold overall, only 25% of this increase occurred during steroid treatment. Most development took place after the cessation of treatment, when milking commenced. Maximum size was not achieved until week 8 of the induced lactation, and was only 70% of normal parenchyma volume. After 18 weeks lactation the activities of three key milk synthetic enzymes were very similar to values previously found in natural lactations, and secretion efficiency (milk production per unit volume of parenchyma) was also similar to that of natural lactations. We conclude that the lower than normal milk yields were associated with incomplete proliferation of mammary tissue, rather than inadequate differentiation of individual secretory cells. PMID- 1856350 TI - Lactational changes in oxytocin release, intramammary pressure and milking characteristics in dairy cows. AB - Two experiments were conducted to investigate possible changes of milking-related oxytocin release (Expt 1) and of intramammary pressure and milking characteristics (Expt 2) throughout entire lactations in German Braunvieh dairy cows. Mean oxytocin concentrations after stimulation at onset of milking increased from 18.3 +/- 15.9 to 30.7 +/- 24.1 pg/ml in Expt 1 and decreased from 23.9 +/- 17.6 to 15.4 +/- 9.1 pg/ml in Expt 2, respectively, but remained above the level necessary to elicit complete milk ejection in both trials. Premilking baseline intramammary pressure had its maximum in early lactation until about month 4 and then decreased to approximately 50% of its initial level. Ejection pressure followed a similar pattern, but dropped only to approximately 75% of its maximum. This was due to the constant elevation of pressure increase, reaching its highest level in late lactation. Time from commencement of stimulation until maximum pressure exceeded 1 min in almost all instances even in early lactation and increased throughout lactation. Despite the normal decrease of milk yield average milk flow fell only slightly while maximum flow rate remained almost constant. Pressure increase, milk yield and milk flow were not different after 1 min and after extended stimulation. Thus there were no indications of a decreasing sensitivity of the milk ejection reflex during lactation, and milking characteristics were positively affected by intense teat stimulation. Suggestions for practical dairying are made. PMID- 1856351 TI - Changes in concentrations of insulin-like growth factor 1, insulin and growth hormone in bovine mammary gland secretion ante and post partum. AB - Concentrations of insulin-like growth factor 1 (IGF-1), insulin and growth hormone were measured in the secretion of the bovine mammary gland from day 70 ante partum until 6 d post partum. Highest levels were found during the last 2 weeks ante partum followed by a rapid decrease during the first milkings post partum. The association of IGF-1 with its binding proteins in milk was analysed and striking differences were found in the distribution of bound and free IGF-1. IGF-1 appeared mainly in the bound form (91%) at days 40-2 ante partum. Free IGF 1 preponderated in the first milkings post partum (73%) and changed again to about 85% in the bound form after day 4 post partum. A slightly acidic pH (6.3) of the secretion was correlated with high amounts of free IGF-1. Gel filtration experiments revealed a possible pH-dependent mechanism for the binding of IGF-1 to its binding proteins in milk. PMID- 1856352 TI - Bacteriological investigations of clinical mastitis in heifers in Sweden. AB - Bacterial analyses were carried out of 2069 udder secretions, isolated from 1481 heifers with mastitis in eight veterinary districts in Sweden. Streptococci, e.g. Streptococcus dysgalactiae and Str. uberis, dominated the bacterial flora, being isolated from 34.4 and 19.5% respectively of heifers with clinical mastitis occurring from puberty up to 14 d post partum. Bacterial species generally regarded as important pathogens in the summer mastitis complex, e.g. Actinomyces pyogenes, Stuart-Schwan coccus and strictly anaerobic bacteria such as Peptostreptococcus indolicus, Fusobacterium necrophorum and Bacteroides melaninogenicus were isolated at low frequencies (13.2, 6.3, 9.4, 3.8 and 1.3% respectively). When the cases of mastitis studied were restricted to those appearing in heifers pre partum, May 15 to October 14 (summer mastitis), these bacterial species were isolated at higher percentages (27.1, 14.4, 21.4, 13.5 and 5.2% respectively). These figures were, nevertheless, still lower than those published in reports from other countries. Whether considered up to 14 d post partum or only pre partum, there were no significant differences in the frequencies of A. pyogenes isolated at different seasons. There were geographical differences in bacterial incidence, e.g. Staphylococcus aureus was isolated significantly more often in northern regions whereas Str. dysgalactiae was more common in the south. This and other Swedish investigations support the theory that A. pyogenes and strictly anaerobic bacteria are 'secondary invaders' that depend on Str. dysgalactiae to cause a primary infection. It is stressed that the udders of all heifers should be examined daily so that cases of mastitis can be treated immediately. PMID- 1856353 TI - Purification of disulphide-linked alpha s2- and kappa-casein from bovine milk. AB - Naturally occurring disulphide-linked alpha s2- and kappa-casein in bovine milk were purified by gel chromatography on a column of Sepharose CL-6B. Four fractions (A-D) were obtained by elution with ammonium acetate-urea buffer. Fractions A and B, identified by SDS gel electrophoresis and amino acid sequence analysis, corresponded to disulphide-linked kappa-casein and alpha s2-casein respectively. Fraction C consisted of a mixture of alpha s1-, alpha s2-, and beta casein. Separation of fraction C into its components was achieved by reversed phase HPLC. The stability of the disulphide bridges in alpha s2- and kappa-casein was shown to differ with respect to reducing agents (dithioerythritol and 2 mercaptoethanol). PMID- 1856354 TI - Ovine lactoferrin: isolation from colostrum and characterization. AB - Highly purified lactoferrin was isolated from ovine colostrum by sequential purification on CM-Sephadex C-50 and Blue-Sepharose, with overall yield of 55%. The ovine lactoferrin was characterized by SDS-PAGE, its amino acid composition and N-terminal sequence to residue 30. Homology with bovine and human lactoferrins was greater than 80 and 50% respectively. Antibodies to ovine lactoferrin were raised in rabbits and used to develop an enzyme-linked immunosorbent assay (ELISA). The antiserum was not cross reactive with other colostrum proteins. PMID- 1856355 TI - American Dairy Science Association. 86th annual meeting. August 12-15, 1991, Logan, Utah. Abstracts. PMID- 1856356 TI - [A diffusion kinetics model of the growth of a cancerous tumor]. AB - Diffusion kinetics model of development of solid tumor has been proposed. This model allows qualitative description of a number of experimental effects, e.g. formation of necrosis zones, change of exponential growth to linear one. Critical parameters for transfer from tumor stabilization mode to its growth have been obtained. Methods of calculation have been elaborated and model calculations have been carried out. PMID- 1856357 TI - [The effect of thymalin on the count of large granular lymphocytes in the peripheral blood of mice with leukemia P388]. AB - Effect of thymaline injections on peripheral blood natural killer cells in mice with p388 leukemia has been studied. The content of natural killers that have been identified as large granular lymphocytes decreased in blood of leukemia mice. Multiple thymaline injections (0.66 mg/kg) maintain the numbers of the lymphocytes at the level of control animals but did not increase the life span of leukemia mice. PMID- 1856358 TI - [The functional activity of the central nervous system in the early postradiation periods after exposure to gamma quanta at different doses]. AB - Behavioral reactions of rats at early postradiation period have been studied after irradiation in sublethal and lethal dose range. Changes in functional activity of the central nervous system develop in correlation with the stages of X-ray damage. PMID- 1856359 TI - [Patterns of highly glycosylated proteins from human saliva]. AB - Mucine-like glycoproteins have been studied by structural indication. Textures of these compounds have been described. Possibility for using mucines as matrix structures in microcrystallographic method of analysis of complex multicomponent systems has been discussed. PMID- 1856360 TI - [The concept of "species--ecological mates" and some obscure points in the evolution of the family of hominids]. AB - Species-ecological twins are the related species that inhabit the same habitats. Both micro- and macroevolution proceeds faster in a system with two such species than in a single species. The hypothesis that evolution of hominids was accelerated by the existence of twin species has been proposed. Species of the Australopithecus genus were twin species for Homo habilis and H. erectus. Both paleontological and cryptozoological data indicate that H. sapiens also has a complimentary species. Small population of the twin species may still exist in obscure parts of the Earth. PMID- 1856361 TI - [The effect of the ligand state of mercury (II) on its coagulating action in relation to human oxyhemoglobin in Tris buffer]. PMID- 1856362 TI - [The "sensory" safety of drugs: photosensitizing damage to the structures of the eye]. AB - Phototoxic side effects of a number of different drugs and natural photosensitizers [correction of photosensors] (psoralenes, psychotropic phenotiazines, anti-malaria drugs, porphirines, adriamycine, etc.) have been analyzed. The ways of study of sensory harmlessness of drugs have been discussed. PMID- 1856363 TI - [Insulin-inducible structural reorganizations in the lipid bilayer of fatty tissue plasma membranes and their age-related characteristics]. AB - Effect of insulin on properties of plasmatic membranes (PM) from adipose tissue of young and aged rats has been studied. Insulin increased the anisotropy of PM. The data obtained indicate that this effect of insulin was specific and was confined to specific domains of the membrane matrix. Both the level of insulin induced structural changes in PM and fluidity of lipid bilayer decreased with age. PMID- 1856364 TI - [The macrosystematics of mammals according to energy metabolism criteria]. AB - Criteria of evolutionary progress and complexity of organization have been proposed on the basis of the data on energetic metabolism. These criteria can serve as a basis of macrosystematics of mammals at the level of orders. The orders with the known data on energetic metabolism have been ranged. PMID- 1856365 TI - [The structural characteristics of the hepatoid circumanal glands in the dog: the intercellular secretory tubules and excretory ducts]. PMID- 1856366 TI - References to contemporary papers on acoustics. PMID- 1856367 TI - Power in nursing. PMID- 1856368 TI - Research in practice: an 'experiment' in researcher-practitioner collaboration. AB - There are signs that researchers and practitioners are seriously attempting to work more closely together to bring research and practice into closer alliance. This paper describes one such attempt in the form of an 'experiment' in collaboration between academic researchers and practising nurses in the undertaking of a practice-based research project. Positive benefits of collaborative research became evident and are highlighted in this paper. No attempt was made to evaluate the 'experiment' objectively and so this is a subjective account, aimed at encouraging other efforts towards closer collaboration between researchers and practitioners in nursing. PMID- 1856369 TI - Quality of care assessed: using the Senior Monitor index in three wards for the elderly before and after a change to primary nursing. AB - Assessments of quality of care using Senior Monitor in three matched wards for elderly patients were carried out on three occasions. The first assessment was carried out in June 1987 as a trial of the measurement tool. The instrument allows for a maximum score of 100. All three wards scored above 60, with two wards scoring above 70. Primary nursing was introduced in one of the wards in January 1988 and the assessment was repeated in June 1988. All ward scores were above 70, with one ward, not the primary nursing ward, scoring above 80. A third assessment was carried out in June 1989. Again, all three wards scored above 70 but this time the primary nursing ward scored 86; the highest ward score of the series. The results for the sub-sections of the assessment are explored in the paper and issues about validity, reliability and inter-rater reliability are discussed. It is argued that Senior Monitor is a useful tool for assessing changes in the quality of care delivered to patients in wards for the elderly but that its full value only becomes apparent with repetition over an extended time period. It may be less appropriate for assessing the impact of a change in the organization of care, not because of any inherent fault in the test but because the very process of using it makes staff look at their practice more critically. It is this critical re-appraisal rather than the change in organization per se which stimulates the improvement in the quality of care. PMID- 1856370 TI - Clients' perceptions: the use of case studies in developing theory. AB - This paper describes some aspects of a study which looked at clients' perceptions of health visiting, and how, if at all, these related to their perceptions of health needs. The researcher explored the alterations of these perceptions over time, and also examined how they related to professional perceptions. The background to this study is described. The methods used are outlined. The study was carried out in two phases. The first phase used semistructured interviews and diaries to explore 41 parents' perceptions at one point in time. In phase two, a series of three semistructured interviews were completed over a 10-month period with 19 primiparous parents, commencing antenatally, and with 10 of their health visitors. Analysis was by the grounded theory method. The eight concept areas which emerged from the data are listed. The paper goes on to discuss the use of case studies in developing a substantive theory. Finally, some of the implications which this study has for health visiting practice are outlined. PMID- 1856371 TI - Critical thinking: impact on nursing education. AB - Critical thinking is considered an essential component of nursing science. As a concept in nursing education, however, critical thinking is not clearly understood nor systematically applied. A survey of deans and directors of baccalaureate and higher-degree schools of nursing accredited by the National League for Nursing examined perceptions of critical thinking as it is currently characterized in nursing education. Results indicated that critical thinking was conceptualized as a variant of the scientific method. It was explicated as a rational-linear problem-solving activity which reflected the nursing process. The findings demonstrated the respondents' lack of clarity about the fullest expression of the mechanisms and operations of critical thinking process and applications. PMID- 1856372 TI - The use of a teaching model to promote reflection and the experiential integration of theory and practice in first-year student nurses: an action research study. AB - This study developed and evaluated an experiential teaching model which aimed to improve the integration of theory and practice for first-year RGN students. This work took a qualitative approach and used Lewin's action research methodology. Using a participant observation approach, data, in the form of diaries, interviews and spot checks, were gathered. To evaluate the teaching model, the spot checks were developed as an indicator of theory-practice integration. The analysis of these spot checks revealed that this teaching approach had value. The strengths and weaknesses of the teaching model, in relation to possible origins of the theory-practice gap, are outlined. The validity of action research is discussed, as are similar issues that are related to the methodology of this study. PMID- 1856373 TI - Developing and documenting a qualitative methodology. AB - Using an ethnographic approach, the phenomenon of the routine of 'doing the obs' (nursing observations of vital signs) was examined with particular reference made to its rationale. This involved a period of fieldwork in a ward which consisted of non-participant observation of the nurses at work and short interviews with them. The experience of the study raised awareness of the research process for the researcher and is explored in detail in this article. The dissemination of such an account offers valuable insight for future researchers and occupies a vital role in determining the validity and reliability of qualitative work. PMID- 1856374 TI - Affective neutrality and involvement in nurse-patient relationships: perceptions of appropriate behaviour among nurses in acute medical and surgical wards. AB - This paper explores ideas about the appropriate basis for nurse-patient relationships which underwrite the nursing practice of experienced staff nurses on the acute surgical and medical wards of a Scottish general hospital. Three central features of involvement with patients are identified, knowledge, reciprocity and investment, and these are related to three general models of the nurse-patient relationship, characterized as primary, demonstrative and associational. The implications of the nursing practice on which these models are based are discussed in the context of issues of quality of care and orientation to work. PMID- 1856375 TI - Service needs of stroke survivors and their informal carers: a pilot study. AB - This pilot study prepares the way for a controlled evaluation of counselling of disabled stroke survivors and their carers. It assesses feasibility of methods and outcome measures potentially useful in the main study. The study elicited information about the psychological, physical, social and service needs, and the feelings of stroke survivors and their informal carers. Twenty patients and their carers were interviewed separately in their own homes. Results describe research tools which were refined, and demonstrate several unmet needs in the psychosocial domain. The main findings were a requirement for more information about stroke and for counselling in relation to 'care' problems arising out of the disability of stroke disease and the changes in dependency produced. PMID- 1856376 TI - Community psychiatric nursing and the depressed elderly: a case for using cognitive therapy. AB - This paper examines whether the literature suggests that Beck's cognitive therapy is a treatment helpful to depressed elderly people, and highlights the issues and adaptations which are considered in its use with this client group. Evidence from outcome studies and case studies is presented which does suggest that it is helpful. A number of issues are raised which require certain special sensitivities on the part of the therapist. Evidence is discussed which suggests that certain adaptations to style and content of therapy may be needed for it to be maximally effective. It is argued that the use of cognitive therapy by community psychiatric nurses (CPNs) could contribute to making the service to depressed elderly people more comprehensive. PMID- 1856377 TI - Institutional loss: an examination of a bereavement reaction in 22 mental nurses losing their institution and moving into the community. AB - Grief has distinctive characteristics. Mental nurses working in a hospital due for closure in 15 months were assessed, and it was found that nurses with long service experienced an anticipatory bereavement in response to the expected loss of their hospital. This reaction is different from the uncomplicated grief which follows the death of a loved person, and is therefore called institutional loss. Twenty-two nurses were assessed, including 13 nurses who were still working in the hospital and nine ex-hospital nurses now working in the community. A sentence completion form was used, together with a measurement of feeling and observed emotion for each sentence. Participants had no prior knowledge about the study. Feelings identified included: initial disbelief; personal anxiety and anxiety about community care; physiological symptoms of anxiety; guilt; anger; feelings of internal loss; avoidance and searching behaviours; acknowledgement of grief; idealization; and identification phenomena. Institutional loss is characterized by: anticipatory grief; an acute stage of mourning in nurses who are physically distanced from the hospital; a refusal to accept closure as 'right'; and a strong identification with the old hospital. Institutional loss in nurses has important implications for the successful rehabilitation of large numbers of patients, and this research suggests that additional support and counselling should be offered. PMID- 1856379 TI - A caring-based AIDS educational model for pre-adolescents: global health human caring perspective. AB - With the prolific messages shown to children today through the media and other sources about acquired immunodeficiency syndrome (AIDS), what sexual questions are on the minds of the fifth and sixth grade students as a result of this exposure? What is the role and responsibility of nurses with regard to this problem? This descriptive study focused on fifth and sixth graders' questions about AIDS and provides some directions for theory-based nursing interventions related to AIDS and children. This paper proposed a theory-based model of caring as a teaching intervention programme about AIDS for pre-adolescents. The model resulted from a sex education programme for fifth and sixth graders in an international school setting in Japan. The nature of the students' questions about AIDS revealed transcultural concerns which suggested that a model of human caring was needed to develop a systematic approach to AIDS education for pre adolescents. The model proposed has global implications for nurses and other health professionals in schools and primary health-care settings in various parts of the world. PMID- 1856378 TI - Comparison of selected college students' and sexually transmitted disease clinic patients' knowledge about AIDS, risk behaviours and beliefs about condom use. AB - Selected college students and sexually transmitted disease (STD) clinic patients of the same age were compared for knowledge about AIDS, use of condoms, sexual behaviours and intentions to engage in various sexual practices. The Theory of Reasoned Action model was used to elicit beliefs about condom use and significant referents who influence condom-use decision making. Eighty-seven per cent of college students were sexually active. College students had significantly fewer sexual partners in a 30-day period than STD patients, but in a 6-month period the mean number of sexual partners was the same for both groups. Significant difference was found in frequency of condom use for subjects with more than one partner. Of the college student sample, 60% did not use condoms compared with 32% of STD patients. Eighteen per cent of college students reported intention to engage in anal intercourse. No STD patients reported such intention. No statistical difference was found between groups on overall knowledge about AIDS: both groups manifested adequate knowledge of basic AIDS-related facts. Significant differences between groups were found in rank order of beliefs about using condoms as well as those referents who influenced decision making. Beliefs about disease, pregnancy, worry and normative influences of sexual partner and friends had the strongest impact on college students. Sexual partner and mother had a strong influence on STD patients' decision making while 'disease', 'pregnancy', 'decreases feeling' and 'decreases partner's pleasure' were among the beliefs influencing condom use. PMID- 1856380 TI - An investigation into why qualified nurses inappropriately describe their own cardiopulmonary resuscitation skills. AB - Recent studies have indicated that significant numbers of nurses are ineffective in performing cardiopulmonary resuscitation (CPR). Furthermore, the studies indicate that many nurses are unable to appraise realistically their own CPR performance. This study sought to ascertain the reasons why qualified nurses are unable or unwilling to appraise themselves realistically with regard to resuscitation skills. The investigation employed both quantitative and qualitative methods to establish the existence of the phenomenon and facilitate its analysis. The findings of the study suggest that unrealistic self-appraisal arises out of poor and infrequent resuscitation training, nurses' attempts to identify with roles which they perceive they should fulfill and past experience of cardiac arrests. The data suggest that current resuscitation training is inadequate, inappropriate and inconsistent for the needs of practising nurses. PMID- 1856381 TI - The effect of employment on the relationship between gender-role preference and self-esteem in married women. AB - The purpose of this study was to examine relationships among gender-role preference, self-esteem and employment category (full-time, part-time, homemaker) while controlling for the effects of income and religion. Data were collected from 79 White married women using the Rosenberg Self-Esteem Scale and a gender role preference scale developed by the author. Findings indicated that: (a) there are significant differences in gender-role preference among categories of employment, with full-time workers having more modern views; (b) category of employment did not influence self-esteem; and (c) women with mixed gender-role preference had lower self-esteem than those with modern gender-role preference. The strength of the relationship between self-esteem and gender-role preference varied by category of employment. Gender-role preference made a significant contribution as a predictor of self-esteem (above and beyond the effects of income and religion) for full-time workers only. PMID- 1856382 TI - Ethnographic traits in the writing of Mary Breckinridge. AB - Mary Breckinridge, founder of The Frontier Nursing Service, employed ethnographic methodologies--participant observation, interviewing and fieldwork--as foundation efforts toward construction of highly responsive health-service systems, developed under circumstances of duress, e.g. after World War I and pre industrial Appalachia. In culturally representing the Appalachian, she drew upon two vast resources, her first-hand field experience as well as her considerable rhetorical skill. She narrated and described an enormity of selected 'realities' of Appalachian life with immediacy of detail and nonpatronizing sensitivity for 'insider' perspectives. In an era of transition with few indigenous cultural writers, Breckinridge capitalized on her family heritage in Appalachia, which further underscored the intimacy and authenticity of her accounts. As portrayed in her autobiography, crosscultural encounters of one kind and time or another supplied an infrastructure of longstanding meaning throughout her life. The final and lasting impression is that, in both skills and orientation, Breckinridge's were essentially those of the ethnographer. PMID- 1856383 TI - The National Practitioner Data Bank. PMID- 1856384 TI - The history and development of the Alabama Dental Association. Voluntary continuing education program. PMID- 1856385 TI - Face masks are flawed. PMID- 1856386 TI - The cruel hoax of rubber gloves. PMID- 1856388 TI - Craniofacial pain--chronic or psychogenic? PMID- 1856387 TI - Ethical and legal duties of a parent to provide dental treatment to a minor. PMID- 1856389 TI - Medical center experiences. PMID- 1856390 TI - Natural adult survival patterns. PMID- 1856392 TI - Cyanotic congenital heart disease: dynamics of oxygen uptake and ventilation during exercise. AB - The presence of intracardiac shunts dissociates the right and left circulations, making dynamic coupling of cellular and pulmonary gas exchange inefficient or impossible. As a result, patients may have profound changes in arterial blood gases and prolongation of adaptation and recovery even with low levels of physical activity. Because the exercise-induced symptoms in patients with cyanotic congenital heart disease have bases apart from heart failure, assignment of a New York Heart Association functional class may be misleading if not erroneous. Dr. Jane Somerville recommends the "Ability Index" shown in Table 1. PMID- 1856391 TI - Cyanotic congenital heart disease: hematologic management. PMID- 1856393 TI - The risks of noncardiac surgery. PMID- 1856394 TI - The physician's responsibilities: residua and sequelae. AB - Cardiologists assuming responsibility for adults with congenital heart disease must have knowledge of electrophysiologic, valvular (native valves), prosthetic (valves, patches and conduits), ventricular (especially chamber function), vascular (especially elevated pulmonary vascular resistance) and noncardiovascular residua and sequelae. Acquired cardiac and noncardiac diseases coexist in older adults with postoperative congenital heart disease and add to the physician's responsibilities. PMID- 1856395 TI - The adult with congenital heart disease: cardiac catheterization as a therapeutic intervention. AB - The adult with congenital heart disease who undergoes cardiac catheterization at the present time is most likely to have complex heart disease and is left with clinically important sequelae or residual defects, ventricular dysfunction or arrhythmias. Residual defects such as paravalvular leaks, coronary fistulas and pulmonary artery narrowings may be corrected with transcatheter techniques. Patients with simple forms of congenital heart disease (for example, atrial septal defect, patent ductus arteriosus, aortic valve stenosis, pulmonary valve stenosis) will go to the catheterization laboratory for treatment, not diagnosis. Certain lesions previously considered benign (for example, patent foramen ovale) may require definitive interventional therapy to reduce the risk of stroke from paradoxic embolism. PMID- 1856396 TI - Electrophysiologic residua and sequelae. PMID- 1856397 TI - Psychosocial concerns and life-style. PMID- 1856398 TI - Insurability and employability. PMID- 1856399 TI - Infective endocarditis: risks and prophylaxis. PMID- 1856400 TI - Assessment of genetic risk in congenital heart disease. PMID- 1856401 TI - Pregnancy and congenital heart disease. PMID- 1856402 TI - Prevalence and prognostic significance of silent and symptomatic ischemia after coronary bypass surgery: a report from the Coronary Artery Surgery Study (CASS) randomized population. AB - The prevalence and prognostic significance of postoperative myocardial ischemia, as detected by exercise testing, were prospectively assessed in 174 patients from the Coronary Artery Surgery Study (CASS) randomized surgical population who had exercise testing before and 6 months after coronary artery bypass graft surgery. Whereas the prevalence of symptomatic ischemia significantly decreased postoperatively (52% vs. 6%, p less than 0.001), the frequency of silent myocardial ischemia did not change (30% vs. 29%). Survival at 12 years after bypass surgery based on the 6-month postoperative exercise test results was significantly better for the 112 patients with no ischemia (80%) than for the 51 patients with silent ischemia (68%) or the 11 patients with symptomatic ischemia (45%). These data show that coronary artery bypass graft surgery diminishes the overall prevalence of symptomatic but not silent ischemia and that both silent and symptomatic ischemia adversely affect the postoperative prognosis of these patients. PMID- 1856403 TI - Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. AB - The Canadian Atrial Fibrillation Anticoagulation Study was a randomized double blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage. As a result of the publication of two other "positive" studies of similar design and objective, this study was stopped early before completion of its planned recruitment of 630 patients. There were 187 patients randomized to warfarin and 191 to placebo. Permanent discontinuation of study medication occurred in 26% of warfarin-treated and 23% of placebo-treated patients. The target range of the international normalized ratio was 2 to 3. For the warfarin-treated patients, the international normalized ratio was in the target range 43.7% of the study days, above it 16.6% of the study days and below it 39.6% of the study days. Fatal or major bleeding occurred at annual rates of 2.5% in warfarin-treated and 0.5% in placebo-treated patients. Minor bleeding occurred in 16% of patients receiving warfarin and 9% receiving placebo. The primary outcome event cluster was nonlacunar stroke, noncentral nervous systemic embolism and fatal or intracranial hemorrhage. Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication. The annual rates of the primary outcome event cluster were 3.5% in warfarin-treated and 5.2% in placebo treated patients, with a relative risk reduction of 37% (95% confidence limits, 63.5%, 75.5%, p = 0.17).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856404 TI - Clinical, physiologic, anatomic and procedural factors predictive of restenosis after percutaneous transluminal coronary angioplasty. AB - In a recent prospective double-blind placebo-controlled trial, a combination of aspirin and dipyridamole was not associated with a reduction in the rate of restenosis within the 1st 6 months after coronary angioplasty. The purpose of this study was to determine whether clinical, anatomic or procedural factors were predictive of the observed restenosis rates in that prospective trial. A total of 247 patients and 280 segments underwent follow-up angiography and quantitative coronary angiographic analysis between 4 and 7 months after coronary angioplasty. Two baseline clinical characteristics--angina class and duration of angina in months--were related to the rate of restenosis by univariate analysis. Patient related stepwise logistic regression analysis identified severity of angina as the only clinical predictor of restenosis. Three univariate baseline anatomic characteristics--percent diameter stenosis before angioplasty, stenosis greater than 10 mm in length and calcific stenosis--and two early postangioplasty characteristics--residual percent diameter stenosis and residual mean pressure gradient--were predictive of restenosis. Of these, only two--length of stenosis and residual percent diameter stenosis--were independently related to restenosis by multivariate analysis and only the former is identifiable before the procedure. It is concluded that in prospective studies in contrast to retrospective studies, few clinical and anatomic factors appear to be predictive of restenosis after coronary angioplasty. PMID- 1856405 TI - Congestive heart failure symptoms in patients with preserved left ventricular systolic function: analysis of the CASS registry. AB - The clinical characteristics and long-term survival of 284 patients from the Coronary Artery Surgery Study (CASS) registry data base who had moderate to severe congestive heart failure symptoms and a left ventricular ejection fraction greater than or equal to 0.45 were studied. A control group consisting of registry patients with an ejection fraction greater than or equal to 0.45 who did not have heart failure was used for comparison. Patients who had heart failure were older and more likely to be female and to have a higher incidence of hypertension, diabetes and chronic lung disease than registry patients who did not have heart failure. As a group, patients with heart failure had more severe angina and were more likely to have had a prior myocardial infarction than were registry patients without heart failure. At 6 year follow-up, 82% of patients in the heart failure group survived compared with 91% of patients in the control group (p less than 0.0001). Multivariate analysis using the Cox proportional hazards model identified the following independent predictors of mortality: regional ventricular systolic dysfunction, number of diseased coronary arteries, advanced age, hypertension, lung disease, diabetes, increased left ventricular end-diastolic pressure and heart failure symptoms. Among patients with heart failure, the 6-year survival rate of those who had three-vessel coronary artery disease was 68% compared with 92% for the group without coronary artery disease. However, the 6-year survival rate for patients with heart failure who underwent surgical revascularization of diseased coronary arteries was not significantly improved compared with that of patients treated medically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856406 TI - Diagnostic value of transesophageal compared with transthoracic echocardiography in infective endocarditis. AB - To compare the diagnostic value of transesophageal and transthoracic echocardiography in infective endocarditis, paired transesophageal and transthoracic echocardiograms were obtained prospectively for 66 episodes of suspected endocarditis in 62 patients. Echocardiographic results were compared with the presence or absence of endocarditis determined by pathologic or nonechocardiographic data from the subsequent clinical course. All echocardiograms were interpreted by an observer told only that the studies were from patients in whom the diagnosis of endocarditis was suspected. The diagnosis of endocarditis was eventually made in 16 of the 66 episodes of suspected endocarditis (14 by pathologic and 2 by clinical criteria). In 7 of 16 transthoracic and 15 of 16 transesophageal echocardiograms, endocarditis was diagnosed at a probability level of "almost certain," giving a sensitivity of 44% and 94%, respectively (p less than 0.01). For the remaining episodes, 49 of 50 transthoracic and all transesophageal studies yielded normal results, giving a specificity of 98% and 100%, respectively. This study suggests that transesophageal echocardiography is highly sensitive and specific for the diagnosis of infective endocarditis and significantly more sensitive than transthoracic echocardiography. Although echocardiography cannot rule out endocarditis, the high diagnostic sensitivity of transesophageal echocardiography results in a low probability of the disease when the study yields negative results in a patient with an intermediate likelihood of the disease. PMID- 1856407 TI - Left atrial spontaneous echo contrast: a clinical and echocardiographic analysis. AB - The clinical and echocardiographic variables related to left atrial spontaneous echo contrast were prospectively evaluated in a consecutive series of 400 patients undergoing transesophageal echocardiography with a 5-MHz single plane transducer. Left atrial spontaneous echo contrast was found in 75 patients (19%) and was significantly associated with atrial fibrillation, mitral stenosis, absence of mitral regurgitation, increased left atrial dimension and a history of suspected embolism. Seventy-one (95%) of the patients with spontaneous echo contrast had atrial fibrillation or mitral stenosis. Anticoagulant therapy had no significant association with spontaneous echo contrast. Multivariate analysis in 89 patients with mitral stenosis or mitral valve replacement showed that spontaneous echo contrast was the only independent predictor (p = 0.03) of left atrial thrombus or suspected embolism, or both. In 60 patients with atrial fibrillation of nonvalvular origin, spontaneous echo contrast (p = 0.01) and age (p = 0.03) were the only independent predictors of left atrial thrombus or suspected embolism, or both. It is concluded that left atrial spontaneous echo contrast is 1) a common finding in patients undergoing transesophageal echocardiography, 2) associated with conditions favoring stasis of left atrial blood, and 3) a marker of previous thromboembolism in patients with nonvalvular atrial fibrillation and those with mitral stenosis or mitral valve replacement. PMID- 1856408 TI - Myocardial ischemia during daily activities: the importance of increased myocardial oxygen demand. AB - The role of increased myocardial oxygen demand in the pathophysiology of myocardial ischemia occurring during daily activities was evaluated in 50 patients with coronary artery disease and exercise-induced ST segment depression. Each patient underwent ambulatory electrocardiographic (ECG) monitoring for ST segment shifts during normal daily activities and symptom-limited bicycle exercise testing with continuous ECG monitoring. All 50 patients had ST depression greater than or equal to 0.1 mV during exercise. A total of 241 episodes of ST depression were noted in the ambulatory setting in 31 patients; only 6% of these were accompanied by angina pectoris. Significant (0.1 mV) ST depression during ambulatory monitoring was preceded by a mean increase in heart rate of 27 +/- 12 beats/min. Patients with ischemia during daily activities developed ST depression earlier during exercise (7.9 +/- 4.4 vs. 14.2 +/- 6.4 min, p less than 0.001) and tended to have significant ECG changes at a lower exercise heart rate and rate-pressure product than did those without ST depression during ambulatory monitoring. In the 31 patients with ischemia during daily activities, the mean heart rate associated with ST depression in the ambulatory setting was closely correlated with the heart rate precipitating ECG changes during exercise testing (r = 0.74, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856409 TI - Hypertrophic cardiomyopathy characterized by marked hypertrophy of the posterior left ventricular free wall: significance and clinical implications. AB - This report describes a subgroup of 17 patients with hypertrophic cardiomyopathy and an unusual and distinctive pattern of left ventricular hypertrophy characterized on echocardiography by marked thickening of the posterior left ventricular free wall and virtually normal or only modestly increased ventricular septal thickness. This distribution of hypertrophy often created a distinctive pattern of "inverted" asymmetry of the posterior wall relative to the septum. The thickness of the posterior wall was 20 to 42 mm (mean 25), while that of the basal ventricular septum was only 12 to 24 mm (mean 17). The left ventricular outflow tract was narrowed because of anterior displacement of the mitral valve within the small left ventricular cavity. Systolic anterior motion of the mitral valve was present in 16 of the 17 patients. The patients ranged in age from 13 to 54 years (mean 31) at most recent evaluation; most (11 of 17, 65%) were severely symptomatic and had experienced important symptoms early in life (before age 40). The condition of only 4 of these 11 patients improved with medical therapy over an average follow-up period of 9 years; however, 6 of the 7 patients who had unsuccessful medical treatment and underwent operation with mitral valve replacement (5 patients) or ventricular septal myotomy-myectomy (1 patient) experienced symptomatic benefit from surgery. The subgroup of patients described in this report underscores the morphologic and clinical diversity that exists within the overall disease spectrum of hypertrophic cardiomyopathy. Characteristically, the patients were young, severely symptomatic and demonstrated evidence of outflow obstruction and an "inverted" asymmetric pattern of posterior free wall left ventricular hypertrophy. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856410 TI - Effects of a meal on hemodynamic function at rest and during exercise in patients with hypertrophic cardiomyopathy. AB - Many patients with hypertrophic cardiomyopathy experience postprandial exacerbation of their symptoms. The vasodilation associated with eating may be deleterious in hypertrophic cardiomyopathy, especially during exercise. To examine the hemodynamic effects of a meal in hypertrophic cardiomyopathy, 11 patients were studied with invasive hemodynamic monitoring during exercise testing in the fasting state and 45 min after a 740 kcal (3,100 J) meal. The meal induced a decrease in systemic vascular resistance index at rest (mean +/- SD, 17 +/- 14%), increases in mean right atrial (31 +/- 21%), mean pulmonary artery (14 +/- 14%) and mean pulmonary capillary wedge (17 +/- 14%) pressures and an increase in cardiac index (18 +/- 10%) due to an increased heart rate without any significant change in stroke volume. During postprandial exercise, heart rate, rate-pressure product, cardiac index and cardiac filling pressures were higher than during fasting exercise and one patient had a decrease in exercise blood pressure compared with the fasting test. Five patients with postprandial exacerbation of symptoms in everyday life had a lesser increase in systemic arterial pressure and stroke volume during both exercise tests and a smaller increase in cardiac index after the meal than did the six patients without postprandial symptom exacerbation, suggesting more severe cardiac disease. It is concluded that patients with hypertrophic cardiomyopathy have an abnormal hemodynamic response to food, in which stroke volume fails to increase and pulmonary capillary wedge and pulmonary artery pressures increase. These adverse changes persist during postprandial exercise and may predispose to exertional collapse in certain patients. PMID- 1856411 TI - Differential effects on right ventricular function of transient right, left anterior descending and left circumflex coronary occlusions during percutaneous transluminal coronary angioplasty. AB - Right ventricular function was studied by means of a thermodilution catheter before, during and after percutaneous transluminal angioplasty of the proximal right (group 1, n = 8), left anterior descending (group 2, n = 8) or left circumflex (group 3, n = 8) coronary artery. All patients had evidence of myocardial ischemia, with single-vessel disease affecting the proximal segment of one of the three major coronary arteries; no patient had had a previous myocardial infarction and all had normal cardiac function at baseline study. Cardiac index decreased during balloon inflation. Mean pulmonary artery pressure was unaffected in group 1 but increased in group 2 (from 19 +/- 5 to 31 +/- 11 mm Hg, p less than 0.01) and in group 3 (from 19 +/- 2 to 22 +/- 5 mm Hg, p less than 0.05). Right ventricular ejection fraction decreased from 62 +/- 9% to 52 +/ 10% (p less than 0.01) in group 1 and from 64 +/- 7% to 44 +/- 10% (p less than 0.005) in group 2, and returned to normal within 2 min after balloon deflation in both groups. In group 3, right ventricular ejection fraction was unchanged during balloon inflation (58 +/- 5% at baseline, 58 +/- 9% at 60 s, p = NS). Therefore, brief occlusion of the proximal segments of the left anterior descending or right coronary artery results in marked alteration of right ventricular performance that is probably caused by right ventricular free wall ischemia in the right coronary group and by the concomitant effects of septal ischemia and increased right ventricular afterload in the left anterior descending artery group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856412 TI - Influence of contrast media on thrombus formation during coronary angioplasty. AB - The influence of contrast media on thrombus formation during percutaneous transluminal coronary angioplasty was assessed in 124 consecutive patients undergoing coronary angioplasty and receiving either ionic (n = 57) (Group I) or nonionic (n = 67) (Group II) contrast medium. The presence of thrombus was assessed by qualitative analysis of angiograms in identical pre- and postangioplasty projections by four observers who had no knowledge of other data. Quantitation of stenosis severity before and after angioplasty and qualitative analysis of lesion eccentricity and complexity and of the presence of dissection were also performed. Although the baseline clinical characteristics of the two groups (including presenting syndromes and procedural and angiographic variables) did not differ, more patients in Group II than Group I developed new thrombus during coronary angioplasty (18% vs. 4%, p less than 0.02). In particular, patients with a presenting syndrome of recent myocardial infarction or rest angina, or both, and patients with an eccentric coronary plaque were more likely to develop new thrombus if they received nonionic than if they received ionic contrast medium (p less than 0.05). Patients with new thrombus formation and patients with thrombus present both before and after angioplasty had a high incidence of acute procedural complications (36% and 23%, respectively). Patients in Groups I and II had a similar incidence of ischemic events during follow-up. PMID- 1856413 TI - Contrast controversy: more to it than meets the eye. PMID- 1856414 TI - Parasympathetic withdrawal is an integral component of autonomic imbalance in congestive heart failure: demonstration in human subjects and verification in a paced canine model of ventricular failure. AB - Although enhanced sympathetic tone is a well recognized component of the autonomic profile characteristic of congestive heart failure, the contribution of parasympathetic withdrawal to this autonomic imbalance is less well described. The technique of spectral analysis of heart rate variability provides a dynamic map of sympathetic and parasympathetic tone and was thus used to define the nature of sympathetic-parasympathetic interactions in humans with idiopathic dilated cardiomyopathy and in a paced canine model of congestive heart failure. Humans with cardiomyopathy were found to have an augmentation of the sympathetically mediated low frequency area of the power density spectrum. Parasympathetic withdrawal was demonstrated by significant reductions in the parasympathetically mediated high frequency area (p less than 0.05) and the ratio of high to low frequency areas (p less than 0.01). Administration of atropine to normal subjects resulted in a significant reduction in the high frequency area (p less than 0.05) and the high/low frequency area ratio, both of which decreased within the range noted in patients with congestive heart failure. Administration of isoproterenol in normal subjects led to an augmentation of the low frequency area but to only a small decrease in the high/low frequency area ratio. Induction of congestive heart failure in a paced canine model resulted in alterations in the autonomic profile that resembled those seen in humans with ventricular failure. The prominent high frequency region of the spectrum at baseline, indicating a predominance of parasympathetic tone, was absent after the evolution of congestive heart failure, and there was a marked augmentation of the low frequency region of the spectrum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856415 TI - Imaging of myocardial infarction in dogs and humans using monoclonal antibodies specific for human myosin heavy chains. AB - The use of three different monoclonal antibodies specific for human ventricular myosin heavy chains in the visualization of the location and extent of necrosis in dogs with experimental acute myocardial infarction and in humans is described. Using a classic immunohistochemical method or ex vivo analysis of heart slices in dogs with acute myocardial infarction subjected to intravenous injection of unlabeled antimyosin antibodies or antimyosin antibodies labeled with indium-111, it was observed that all antibody fragments specifically reached the targeted necrotic zone less than 2 h after antibody injection and remained bound for up to 24 h. In a limited but significant number of cases (5 of the 12 humans and 11 of 43 dogs), it was possible to image the necrotic zone in vivo as early as 2 to 4 h after antibody injection. In other cases, individual blood clearance variations retarded or even prevented in vivo necrosis detection. Higher antimyosin fixation values were obtained in the necrotic zones in dogs with a rapid blood clearance relative to that of the other dogs. It is concluded that antimyosin antibodies always reached necrotic areas within 2 h. If blood clearance was rapid, in vivo imaging of the necrotic area was possible 2 to 6 h after necrosis, even in humans. In some cases, however, uncontrolled individual variations in the timing required for sufficient blood clearance hampered this rapid in vivo detection of myocardial necrosis. PMID- 1856416 TI - Comparison of coronary vasodilation with intravenous dipyridamole and adenosine. AB - Although both intravenous dipyridamole and adenosine have been used to produce coronary vasodilation during cardiac imaging, the relative potency of the commonly administered doses of these agents has not been evaluated. Accordingly, the coronary and systemic hemodynamic effects of intravenous adenosine (140 micrograms/kg per min) and intravenous dipyridamole (0.56 mg/kg over 4 min) were compared with a maximally dilating dose of intracoronary papaverine in 15 patients. Coronary blood flow responses were assessed using a Doppler catheter in a nonstenotic coronary artery. The protocol was discontinued in two patients because of transient asymptomatic atrioventricular (AV) block during adenosine infusion. The mean heart rate increased more with adenosine (11 +/- 9 beats/min) and dipyridamole (11 +/- 7 beats/min) than with papaverine (4 +/- 3 beats/min, p less than 0.05 vs. adenosine and papaverine). The mean arterial pressure decreased less with dipyridamole (-10 +/- 3 mm Hg) and papaverine (-9 +/- 4 mm Hg) than with adenosine (-16 +/- 5 mm Hg, p less than 0.01 vs. dipyridamole and papaverine). The peak/rest coronary blood flow velocity ratio was greater with papaverine (3.9 +/- 1.1) than with adenosine (3.4 +/- 1.2, p less than or equal to 0.05 vs. papaverine) or dipyridamole (3.1 +/- 1.2, p less than 0.01 vs. papaverine). A larger decrease in coronary resistance as measured by the coronary vascular resistance index occurred with papaverine (0.25 +/- 0.06) and adenosine (0.26 +/- 0.09) than with dipyridamole (0.31 +/- 0.10, p less than 0.01 vs. papaverine, p less than 0.05 vs. adenosine).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856418 TI - Effect of peripheral cardiopulmonary bypass on left ventricular size, afterload and myocardial function during elective supported coronary angioplasty. AB - Although cardiopulmonary bypass support has been increasingly used for high risk coronary angioplasty, few data exist regarding its effects on left ventricular function. Accordingly, in 20 patients changes in left ventricular size, afterload and myocardial function were assessed by continuous hemodynamic monitoring and simultaneous two-dimensional echocardiography during cardiopulmonary bypass supported high risk angioplasty. The cross-sectional left ventricular area during bypass support remained unchanged during diastole, whereas during systole it decreased (from 29.6 +/- 11.4 to 27.6 +/- 10.4 cm2, p less than 0.05). Global left ventricular function expressed as fractional area change remained unchanged from baseline to bypass support but decreased during balloon inflation (from 0.27 +/- 0.11 to 0.17 +/- 0.09, p less than 0.001). The end-systolic meridional wall stress decreased during bypass support (from 141 +/- 75 to 110 +/- 58 x 10(3) dynes/cm2, p less than 0.02). Regional myocardial function was assessed by a wall motion score (0 = normal, 1 = hypokinesia, 2 = akinesia and 3 = dyskinesia). Regions supplied by a stenotic (greater than or equal to 50% diameter) vessel deteriorated during bypass support (score from 0.9 +/- 0.8 to 1.06 +/- 0.8, p less than 0.01), whereas regions supplied by a nonstenotic vessel did not. Regions supplied by the target vessel deteriorated further during balloon inflation (score from 0.7 +/- 0.6 to 1.7 +/- 0.75, p less than 0.001). Thus, although left ventricular size and global function remain unchanged and afterload decreases during bypass support, myocardial dysfunction in regions supplied by a stenotic vessel may occur. Furthermore, regional and global left ventricular dysfunction still occur with angioplasty balloon inflation during cardiopulmonary bypass support. PMID- 1856417 TI - Respiratory muscle deoxygenation during exercise in patients with heart failure demonstrated with near-infrared spectroscopy. AB - Exertional dyspnea in patients with heart failure may be due, in part, to respiratory muscle underperfusion. Near-infrared spectroscopy is a new technique that permits noninvasive assessment of skeletal muscle oxygenation by monitoring changes in near-infrared light absorption. With use of near-infrared spectroscopy, serratus anterior muscle oxygenation during maximal bicycle exercise was compared in 10 patients with heart failure (ejection fraction 16 +/- 5%) and 7 age-matched normal subjects. Oxygen consumption (VO2), minute ventilation (VE) and arterial saturation were also measured. Changes in difference in absorption between 760 and 800 nm, expressed in arbitrary units, were used to detect muscle deoxygenation. Minimal change in this difference in absorption occurred in normal subjects during exercise, whereas patients with heart failure exhibited progressive changes throughout exercise consistent with respiratory muscle deoxygenation (peak exercise: normal 3 +/- 6, heart failure 12 +/- 4 near-infrared arbitrary units, p less than 0.001). At comparable work loads patients with heart failure had significantly greater minute ventilation and respiratory rate but similar tidal volume when contrasted with normal subjects. However, at peak exercise normal subjects achieved significantly greater minute ventilation and tidal volume with a comparable respiratory rate. No significant arterial desaturation occurred during exercise in either group. These findings indicate that respiratory muscle deoxygenation occurs in patients with heart failure during exercise. This deoxygenation may contribute to the exertional dyspnea experienced by such patients. PMID- 1856419 TI - Influence of balloon size and stenosis morphology on immediate and delayed elastic recoil after percutaneous transluminal coronary angioplasty. AB - After successful coronary angioplasty, the minimal luminal diameter of the dilated coronary artery segment is generally smaller than the diameter of the largest balloon catheter at the maximal inflation pressure. The determinants of this phenomenon were studied in 28 patients. Biplane angiograms were obtained after intracoronary administration of isosorbide dinitrate (1 mg) before, immediately and 24 h after coronary angioplasty. Balloon and coronary luminal diameters were measured by automated contour detection. Immediately after the procedure, the difference between inflated balloon diameter and minimal luminal diameter averaged 0.93 +/- 0.43 mm for the entire group and was greater both in eccentric stenoses (1.13 +/- 0.39 vs. 0.70 +/- 0.36 mm; p less than 0.01) and after angioplasty with an oversized balloon (1.20 +/- 0.37 vs. 0.71 +/- 0.33 mm; p less than 0.005). At 24 h, the balloon - minimal luminal diameter difference was unchanged at the group level (0.86 +/- 0.38 mm, but the minimal luminal diameter increased significantly in the subgroup of coronary segments dilated with an oversized balloon (1.97 +/- 0.37 vs. 1.81 +/- 0.28 mm; p less than 0.05). Thus, the difference between the minimal diameter of a dilated coronary segment immediately after a successful coronary balloon angioplasty procedure and the maximal diameter of the inflated balloon catheter is dependent both on eccentricity of the stenosis and on the balloon/artery diameter ratio. Moreover, the increase in minimal luminal diameter 24 h after angioplasty performed with an oversized balloon suggest that in addition to elastic recoil partly reversible factors related to vessel barotrauma are involved. PMID- 1856420 TI - Quantification of absolute myocardial perfusion at rest and during exercise with positron emission tomography after human cardiac transplantation. AB - The maximal exercise capacity of cardiac transplant recipients is reduced compared with that of normal subjects. To determine if this reduced exercise capacity is related to inadequate myocardial perfusion during exercise, myocardial perfusion was measured noninvasively with use of positron emission tomography and nitrogen (N)-13 ammonia. Twelve transplant recipients with no angiographic evidence of accelerated coronary atherosclerosis were studied. Serial N-13 ammonia imaging was performed at rest and during supine bicycle exercise. The results were compared with those from 10 normal volunteers with a low probability of having cardiac disease. A two-compartment kinetic model for estimating myocardial perfusion was applied to the data. Transplant recipients achieved a significant lower exercise work load than did the volunteers (42 +/- 16 vs. 128 +/- 22 W), but a higher venous lactate concentration (31.3 +/- 14.9 vs. 13.7 +/- 4.1 mg/100 ml). Despite the difference in exercise work load, there was no significant difference in the cardiac work achieved by transplant recipients and normal subjects as evidenced by similar rate-pressure products of 24,000 +/- 3,400 versus 21,300 +/- 2,800 betas/min per mm Hg, respectively. In addition, myocardial blood flow during exercise was not significantly different between the two groups (1.70 +/- 0.60 vs. 1.56 +/- 0.71 ml/min per g, respectively). This study demonstrates that the myocardial flow response to the physiologic stress of exercise is appropriate in transplant recipients and does not appear to explain the decreased exercise capacity in these patients. PMID- 1856421 TI - Transesophageal Doppler echocardiography of pulmonary venous flow: a new marker of mitral regurgitation severity. AB - Pulmonary venous flow varies with different cardiac conditions. Flow patterns in response to mitral regurgitation have not been well studied, but flows may vary enough to differentiate among different grades of regurgitation. Accordingly, pulmonary venous flow velocities were recorded in 50 consecutive patients referred for outpatient (n = 26) or intraoperative (mitral valve repair; n = 24) echocardiographic examination for mitral regurgitation. Recordings were made of right and left upper pulmonary veins with pulsed wave Doppler transesophageal echocardiography. Mitral regurgitation was graded from 1+ to 4+ by an independent observer using transesophageal color flow mapping. The results of cardiac catheterization performed 5 weeks earlier in 43 of the patients were also graded for mitral regurgitation by an independent observer. Pulmonary venous flow patterns, the presence of reversed systolic flow and peak systolic and diastolic flow velocities were compared with the severity of mitral regurgitation indicated by each technique. Of the 28 patients with 4+ regurgitation by transesophageal color flow mapping, 26 (93%) had reversed systolic flow. The sensitivity of reversed systolic flow in detecting 4+ mitral regurgitation by transesophageal color flow mapping was 93% and the specificity was 100%. The sensitivity and specificity of reversed systolic flow in detecting 4+ mitral regurgitation by cardiac catheterization were 86% and 81%, respectively. Discordant flows were observed in 9 (24%) of 38 patients; the left vein usually showed blunted systolic flow and the right showed reversed systolic flow. In 22 intraoperative patients, there was "normalization" of pulmonary venous systolic flow after mitral valve repair in the postcardiopulmonary bypass study compared with the prebypass study after the mitral regurgitant leak was corrected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856422 TI - Predictive accuracy of electrophysiologic localization of accessory pathways. AB - Operative ablation of accessory pathways depends critically on preoperative localization when technical limitations preclude complete intraoperative mapping. To assess the accuracy of localization, 345 patients undergoing operative ablation were studied; 316 (91.6%) had a single accessory pathway and 29 (8.4%) had multiple accessory pathways. The electrophysiologic study was diagnostically complete and accurate in 294 patients (93%) with a single accessory pathway and 19 (61%) with multiple accessory pathways. A left lateral accessory pathway was most accurately localized with excellent sensitivity (99%) and positive predictive value (98.5%). Diagnostic errors occurred in 33 patients because of 1) incorrect localization (n = 16), 2) failure to detect a second pathway (n = 9), and 3) diagnosis of a second pathway not verified intraoperatively (n = 8). Multiple pathways were more prevalent in the group with errors (33.3% vs. 5.8%, p = 0.0001), as were unidirectional pathways (48.5% vs. 24.3%, p = 0.003). It is concluded that preoperative localization of accessory pathways is sufficiently accurate to allow intraoperative mapping to be brief and focused. PMID- 1856423 TI - Doppler echocardiography of fetal ductus arteriosus constriction versus increased right ventricular output. AB - A prospective longitudinal study from 121 examinations of 41 normal pregnant women showed that fetal ductal flow velocities increased with gestational age. These normal data were compared with data in three groups of fetuses with altered ductal flow velocities: 22 fetuses (mean gestational age 31.3 weeks) had ductal constriction due to maternal indomethacin treatment; 10 fetuses (mean gestational age 27.9 weeks) had been exposed to terbutaline, a positive inotropic agent and 14 fetuses (mean gestational age 33.3 weeks) had hypoplastic left heart syndrome. In normal fetuses maximal systolic, mean and end-diastolic ductal flow velocities increased linearly (p less than 0.0001). The pulsatility index did not change (mean +/- 2 SD: 2.46 +/- 0.52). Fetuses with ductal constriction had higher maximal, mean and end-diastolic flow velocities and a significantly lower pulsatility index than did normal fetuses (1.25 +/- 0.76; p less than 0.0005). Six of 10 fetuses of the terbutaline group and 8 of 14 fetuses with hypoplastic left heart syndrome had increased maximal flow velocity, but normal or only mildly elevated mean flow velocity. The pulsatility index in fetuses during terbutaline therapy and with hypoplastic left heart syndrome was significantly higher than in normal fetuses (3.11 +/- 0.46 and 3.09 +/- 0.7, respectively, vs. 2.46 +/- 0.52; p less than 0.0005). Fetal ductal waveform analysis was necessary to distinguish fetal ductal constriction from increased right ventricular output. These measurements may be helpful in the diagnosis of left-sided outflow obstruction and assessment of fetal hemodynamic data. PMID- 1856424 TI - Intraoperative transesophageal echocardiography of atrioventricular septal defect. AB - To determine the accuracy and utility of single-plane transesophageal echocardiography in analyzing atrioventricular (AV) septal defect, intraoperative transesophageal echocardiography was performed before and after institution of cardiopulmonary bypass in 16 patients (age 24 days to 14 years, weight 3 to 47 kg). Prebypass transesophageal echocardiography (including two-dimensional echocardiography, Doppler color flow mapping and pulsed wave Doppler ultrasound) correctly diagnosed divided AV valve, common AV valve and unbalanced AV valve, as well as atrial or ventricular septal defect, or both, in all cases. It correctly analyzed AV valve regurgitation in all 10 patients with right and all 14 with left AV valve regurgitation and correctly analyzed 30 of 33 additional cardiac anomalies. Transesophageal echocardiography was able to detect the absence of normal pulmonary venous connections but failed to demonstrate all of the complex anomalous pulmonary venous connections in three patients with atrial isomerism. Postbypass transesophageal echocardiography documented the absence of a significant residual shunt in 11 of 11 patients undergoing corrective surgery and verified residual AV valve regurgitation in 7 of 9 patients with tricuspid regurgitation and 11 of 13 with mitral regurgitation. Transesophageal echocardiographic information that altered or refined the surgical treatment was obtained in 5 (31%) of 16 patients. Epicardial and transesophageal echocardiography results were concordant in all 13 patients in whom both were performed. Transesophageal echocardiography provides useful and accurate imaging of the important two-dimensional, pulsed wave Doppler ultrasound and Doppler color flow mapping features in AV septal defect. PMID- 1856425 TI - Early surgical closure of a large ventricular septal defect: influence on long term growth. AB - The pre- and postoperative growth patterns of 52 otherwise normal infants undergoing primary surgical closure of a large ventricular septal defect before 7 months of age were reviewed. Serial measurements of weight, length and head circumference were compiled for all patients preoperatively and in 46 long-term survivors and were expressed as Z scores (in standard deviations from the mean for age and gender). By the time of surgery at a mean age of 0.33 year, the mean weight, length and head circumference Z scores of all 52 infants were -2.9, -0.9 and -0.6, respectively, and were all significantly below normal (p less than 0.001). At a mean age of 5.7 years, the mean weight, length and head circumference Z scores of 35 patients of normal birth weight were normal or varied only marginally from those of the reference population (-0.4, -0.1 and +0.5, respectively; p less than 0.02, p greater than 0.05 and p = 0.008, respectively) and did not differ significantly in any variable from those of 44 normal siblings. However, among 11 infants with a low birth weight, all three variables remained abnormal at long-term follow-up when compared with the reference population (-1.7, -1.7 and -0.9, respectively; p less than 0.001 for each) and 22 normal siblings (p less than or equal to 0.008).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856426 TI - Double-inlet single left ventricle: echocardiographic anatomy with emphasis on the morphology of the atrioventricular valves and ventricular septal defect. AB - The echocardiographic anatomy of double-inlet single left ventricle was studied in 57 patients, aged 1 day to 27 years (mean 6 years); the variables examined included morphology, size and function of the atrioventricular (AV) valves and ventricular septal defect and their relation to pulmonary stenosis, aortic stenosis and aortic arch obstruction. The visceroatrial situs was solitus and the heart was in the left side of the chest in all 57 patients. A d-loop ventricle was present in 21 patients and an l-loop ventricle in 36. The great arteries were normally related (Holmes heart) in 8 patients and transposed in 49. In all hearts, the right AV valve was anterior to the left AV valve. In 53 patients, the tricuspid valve (right valve in d-loop and left valve in l-loop) was closer to and had attachments on the septum. The tricuspid valve straddled the outflow chamber in eight patients. No significant difference was noted in the mean AV valve diameter when comparing mitral and tricuspid valves within the same group or between the groups with a d- or l-loop ventricle. The right AV valve diameter had a significant direct correlation with the aortic valve diameter and the size of the ventricular septal defect regardless of ventricular loop. Both AV valves were functionally normal in 34 patients. Among patients with AV valve dysfunction, the tricuspid valve tended to be stenotic in patients with an l-loop ventricle and regurgitant in patients with a d-loop ventricle. Mitral valve dysfunction was uncommon. The ventricular septal defect (46 patients) was separated from the semilunar valves in 24 patients (muscular defect) and adjacent to the anterior semilunar valve as a result of hypoplasia or malalignment, or both, of the infundibular septum (subaortic defect) in 19 patients. Multiple defects were present in three patients. The defect was unrestrictive in 26 patients, restrictive in 23 and could not be evaluated in 8. Pulmonary artery banding had been performed in 8 of the 26 patients with an unrestrictive defect and in 10 of the 23 patients with a restrictive defect. Only 4 of 19 subaortic defects compared with 16 of 24 muscular defects were restrictive. The size of the defect was significantly correlated with the measured pressure gradient. Among patients with transposition, only 2 of 13 with pulmonary stenosis had a restrictive ventricular septal defect compared with 15 of 30 without pulmonary stenosis. In patients with transposition, the defect size was significantly smaller when coarctation was present. PMID- 1856427 TI - Transesophageal real-time echocardiography in infants and children with congenital heart disease. AB - Transesophageal echocardiography using Doppler color flow mapping with both single plane transverse and longitudinal pediatric probes was performed in 127 infants and children both intraoperatively and postoperatively. The 127 patients ranged in age from 1 day to 18 years (mean 37 months) and in weight from 2.4 to 45 kg (mean 13.2); 157 studies were successfully performed (100% of attempted) with no complications. Transesophageal two-dimensional echocardiography combined with pulsed wave Doppler ultrasound and color flow mapping provided detailed morphologic as well as physiologic information, with additional information provided overall in 56% of the cases. Typical limitations of single-plane transverse imaging were overcome using a prototype longitudinal-axis pediatric probe. Both left and right ventricular outflow tracts, distal pulmonary arteries and all of the interventricular and atrial septa were visualized. Assessment of surgical repair intraoperatively as well as assessment postoperatively for cardiac function, residual intracardiac shunts, residual valvular sequelae and other hemodynamic events was important and easily performed in an otherwise inaccessible patient. Transesophageal echocardiography in infants and in small children is a valuable "noninvasive" imaging technique that offers important additional and complementary information. PMID- 1856428 TI - Repetitive sinoatrial exit block as the major mechanism of drug-provoked long sinus or atrial pause. AB - Prolonged sinus or atrial pause occurred in six patients with paroxysmal supraventricular tachycardia after drug administration. All six patients had normal sinus node function during control electrophysiologic study; the sinus cycle length ranged from 510 to 900 ms (mean 743 +/- 141) and the longest sinus node recovery time ranged from 800 to 1,230 ms (mean 1,018 +/- 168). A long sinus or atrial pause occurring at the termination of tachycardia or cessation of atrial pacing, ranging from 3,100 to 8,200 ms (mean 6,270 +/- 1,674), was provoked by the administration of various drugs. These included an intravenous bolus injection of adenosine triphosphate (5 mg; one patient), intravenous bolus injection of verapamil (5 mg; one patient), a combination of a single oral dose of diltiazem (120 mg) and propranolol (20 to 40 mg; three patients), oral diltiazem (240 mg/day; one patient) and a combination of oral diltiazem (240 mg/day) and propranolol (160 mg/day; one patient). In five patients, low frequency deflections suggestive of sinus node activity with a cycle length between 620 and 3,500 ms were recorded during pauses. These findings suggest that repetitive sinoatrial exit block was responsible for the pause. Sinus slowing with a long arrest suggesting suppression of sinus automaticity was also noted in three of these five patients; the longest sinus arrest in these three patients was 4,160, 4,800 and greater than 4,910 ms, respectively. The remaining patient with a pause of 6,840 ms had no recordable sinus activity, either reflecting suppression of sinus automaticity or technical failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856429 TI - Effect of long-term enalapril therapy on cardiopulmonary exercise performance in men with mild heart failure and previous myocardial infarction. AB - Forty-one men with documented myocardial infarction greater than 6 months previously were randomized to long-term (48 weeks) therapy with placebo or enalapril on a double-blind basis. All patients were receiving concurrent therapy with digitalis and a diuretic drug for symptomatic heart failure (functional class II or III). The mean age was 64 +/- 7.3 years and no patient suffered from exertional chest pain. Patients underwent maximal cardiopulmonary exertional chest pain. Patients underwent maximal cardiopulmonary exercise testing to exhaustion on an ergometer cycle nine times over the course of 48 weeks. Gas exchange data were collected on a breath by breath basis with use of a continuous ramp protocol. In the placebo group (n = 21), the mean (+/- SD) peak oxygen consumption (VO2) at baseline was 18.8 +/- 5.2 versus 18.5 +/- 5.5 ml/kg per min at 48 weeks (-1.4%, p = NS). In the enalapril group (n = 20), the corresponding values were 18.1 +/- 3.1 versus 18.3 +/- 2.6 ml/kg per min (+2.8%, p = NS). The mean VO2 at the anaerobic threshold for the placebo group at baseline study was 13.1 +/- 3.5 versus 12.8 +/- 2.1 ml/kg per min at 48 weeks (-2.2%, p = NS). The corresponding values for the enalapril group were 11.8 +/- 2.3 versus 11.8 +/- 2.4 ml/kg per min (+1.4%, p = NS). The mean total exercise duration in the placebo group at baseline study was 589 +/- 153 versus 620 +/- 181 s at 48 weeks (+5.4%, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856430 TI - Pharmacokinetic analysis of coronary venous retroinfusion: a comparison with anterograde coronary artery drug administration using metoprolol as a tracer. AB - Plasma and myocardial tissue concentrations of metoprolol were studied in ischemic and nonischemic areas of 22 pigs after 90 (n = 19) and 16 (n = 3) min of left anterior descending coronary artery occlusion. Group A (n = 6) received simultaneous intravenous metoprolol (0.2 mg/kg body weight) and tritium-labeled (3H)-metoprolol (0.2 mg/kg) retrogradely into the coronary vein. In group B (n = 5), metoprolol and 3H-metoprolol were administered in the same way, but at half the volume to study the influence of derived coronary venous pressure on the myocardial concentration of drug. In group C (n = 3), metoprolol was given retrogradely and saline solution was infused into the left anterior descending artery before induced death to wash out metoprolol from the coronary veins. To rule out a possible influence of the development of myocardial necrosis on drug distribution, metoprolol was retroinfused after 1 min of arterial occlusion in three pigs (group D). In group E (n = 5), metoprolol (0.2 mg/kg) was infused anterogradely into the left anterior descending artery. Peak plasma concentration was significantly higher after intravenous infusion of metoprolol (1,188 +/- 503 nmol/liter) than after coronary venous infusion (417 +/- 155 nmol/liter; p less than 0.001). In groups A and B, the nonischemic myocardial concentration of metoprolol was 250 to 300 pmol/g, whether the drug was infused intravenously or into the coronary vein. Coronary venous retroinfusion, however, resulted in a substantial accumulation of metoprolol in the ischemic myocardium. In group A pigs, subendocardial myocardial concentration was 16,800 +/- 7,774, mid myocardial 39,590 +/- 18,043 and subepicardial 57,143 +/- 29,030 pmol/g (mean +/- SE). The ischemic myocardial concentration in pigs from group B was somewhat less pronounced, probably secondary to a lower coronary venous pressure (15 +/- 3 mm Hg) with the lower volume of infusion (6.1 +/- 0.3 ml) in group B compared with 32 +/- 5 mm Hg with a 14 +/- 1 ml infusion in group A. Coronary artery anterograde administration resulted in myocardial ischemic and nonischemic zone drug concentrations similar to those observed after retroinfusion into the coronary vein. With both modes of administration, there was a transmyocardial gradient from a somewhat lower drug concentration in the subendocardium, toward an increasing level in the mid-myocardium, to the highest concentration in the subepicardial zone of the ischemic myocardium. Coronary venous retroinfusion resulted in pronounced drug accumulation in the ischemic myocardium. The derived coronary venous pressure during infusion influenced the concentration of drug.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1856431 TI - Coronary venous retroinfusion of deferoxamine reduces infarct size in pigs. AB - The efficacy of coronary venous retroinfusion of the iron chelator deferoxamine was studied in 24 pentobarbital-anesthetized open chest pigs with a 60 min occlusion of the left anterior descending coronary artery followed by 3 h of reperfusion. Eight retrogradely treated pigs were given 10 mg/kg body weight of deferoxamine by way of the anterior interventricular vein and eight systemically treated pigs received the same doses of deferoxamine intravenously. Drug infusions lasted for 5 min, beginning 15 min before reperfusion. Eight control pigs received systemic intravenous saline solution. Myocardial area at risk and necrotic area were assessed by the monastral blue dye and the triphenyltetrazolium chloride staining method, respectively. There were no significant differences in hemodynamics or regional myocardial function (sonomicrometry) among the groups. Infarct size expressed as percent of risk area was 73.9 +/- 13.5% in the control group, 70.6 +/- 16.4% in the systemically treated group and 48.5 +/- 21.4% (p less than 0.05) in the retrogradely treated group. In conclusion, deferoxamine significantly reduced infarct size after coronary occlusion only when given regionally by way of the coronary vein. Because there was no significant hemodynamic effect caused by deferoxamine infusion, it is suggested that this drug prevents postischemic reperfusion injury by a direct cardioprotective effect. PMID- 1856432 TI - Cardioplegia by way of the coronary sinus for valvular and coronary surgery. AB - Retrograde coronary sinus perfusion has recently reemerged as an attractive means of delivering cardioplegic solutions during open heart procedures. In patients undergoing aortic valve or aortic root surgery, there is no evidence that coronary sinus cardioplegia results in a better myocardial protection than that achieved with the use of standard methods of anterograde cardioplegia delivery. However, the retrograde approach provides distinct technical advantages that might favor its use as an alternative to direct coronary ostial cannulation. In select subgroups of patients undergoing coronary bypass procedures, there is a growing body of evidence that the coronary sinus route may be more effective than the anterograde route because of its superior capacity to ensure homogeneous distribution of cooling and cardioplegia in myocardial areas supplied occluded arteries. The well established safety of coronary sinus cardioplegia in the clinical setting further justifies its inclusion among techniques for ensuring adequate myocardial preservation during surgically induced ischemic arrest. PMID- 1856433 TI - ACC policy statement. Recommended guidelines for training in adult clinical cardiac electrophysiology. Electrophysiology/ Electrocardiography Subcommittee, American College of Cardiology. AB - Training in clinical cardiac electrophysiology should take place in an Accreditation Council for Graduate Medical Education accredited cardiology program, and the electrophysiology training program itself should be accredited by the Council. Each trainee must be eligible for board certification in Internal Medicine and either eligible for certification in Cardiovascular Diseases or in a program leading to eligibility. Training faculty should be certified in clinical cardiac electrophysiology or demonstrate equivalent credentials. At least two training faculty members are preferred. The faculty must be dedicated to teaching, active in performing or promoting research and must spend a substantial portion of their time in research, teaching and practice of clinical electrophysiology. A curriculum of training should be established. Faculty experts in the related basic sciences should be available and involved in teaching. The institution should have a fully equipped clinical electrophysiology laboratory and complete noninvasive capabilities. A close working relation with a cardiac surgery faculty member skilled in surgical treatment of arrhythmias is required. Training in application of pharmacologic and all current nonpharmacologic therapies, in the outpatient and inpatient setting, is necessary. The clinical exposure must include all facets of arrhythmia diagnosis and treatment and must be quantitatively sufficient to allow the trainee to develop proficiency. The period of training should not be less than one year in addition to the period of cardiology fellowship required by the ABIM for board eligibility. A continuous period of training is preferred. PMID- 1856434 TI - Angioscopy after coronary excimer laser angioplasty. PMID- 1856435 TI - Cardiac-specific antibodies in dilated cardiomyopathy. PMID- 1856436 TI - Some comments on masochism and the delusion of omnipotence from a developmental perspective. AB - This paper explores the relation of the delusion of omnipotence to masochism and suggests that this fantasy constitutes a major component of the resistance so prominent in work with masochistic patients. The connections among masochism, omnipotence, negative therapeutic reaction, and clinging to pain are discussed. The classical view has been that the failure of infantile omnipotence forces the child to turn to reality. Our experience with masochistic patients suggests that it is the real failure to achieve competent interactions with others that forces the child to turn to omnipotent solutions. The distinction is made between fantasies that enhance the real capacities of the self and those aimed at denying and transforming the pain and inadequacy of the mother-child relationship. The epigenetic transformations of omnipotent fantasies through all levels of development are described. The patient's need to protect the omnipotent fantasy is discussed in relation to resistance at each phase of analysis. PMID- 1856437 TI - Sadomasochism, sexual excitement, and perversion. AB - Sadomasochism, an ingredient of infantile sexuality, is an essential part of normal sexual functioning and love relations, and of the very nature of sexual excitement. Sadomasochistic elements are also present in all sexual perversions. Sadomasochism starts out as the potential for erotic masochism in both sexes, and represents a very early capacity to link aggression with the libidinal elements of sexual excitement. Sexual excitement may be considered a basic affect that overcomes primitive splitting of love and hatred. Erotic desire is a more mature form of sexual excitement. Psychoanalytic exploration makes it possible to uncover the unconscious components of sexual excitement: wishes for symbiotic fusion and for aggressive penetration and intermingling; bisexual identifications; the desire to transgress oedipal prohibitions and the secretiveness of the primal scene, and to violate the boundaries of a teasing and withholding object. The relation between these wishes and the development of erotic idealization processes in both sexes is explored in the context of a critical review of the pertinent psychoanalytic literature. PMID- 1856438 TI - Sadomasochism in the neuroses conceived of as a pathological compromise formation. AB - Masochistic phenomena in adults are discussed as derivatives of conscious and/or unconscious fantasies. These masochistic fantasies are always associated with conscious and/or unconscious narcissistic and sadistic fantasies. These fantasies, like all fantasies in adults, are conceived of as compromise formations. After a selected review of the literature, analytic data are presented to highlight the clinical advantages of a contemporary elaboration of the structural hypothesis for the understanding of sadomasochistic and sadonarcissistic phenomena. PMID- 1856439 TI - The dread to repeat: comments on the working-through process in psychoanalysis. AB - This paper focuses on the process of working through in psychoanalysis. Reemphasis of the centrality of the empathic listening perspective and discovery of the selfobject transferences made it necessary to reconceptualize various aspects of the analytic process from the perspective of psychoanalytic self psychology. With the help of a clinical vignette, the paper illustrates the manner in which archaic defense organizations and newly developing psychic structures find a compromise solution in a transference symptom. Such symptoms can serve as nodal points in the process of working through; they represent a transitional phase between the old automatic responses to narcissistic injury and an increased capacity to use signal anxiety. The psychopathology that became illuminated in this process can be described phenomenologically as a self defeating personality disorder. PMID- 1856440 TI - Sadomasochism in the perversions: some thoughts on the destruction of reality. AB - The author summarizes and develops some of her viewpoints on the perversions (outlined in several of the books and articles she has written). For her all the perversions, whatever their content, develop against an anal sadomasochistic backdrop. Their aim is to destroy reality. Reality, from a psychosexual perspective, may be defined as resulting from the existence of the father separating the mother and the child. This may be formulated in another way: reality is recognition of sexual and generational differences. Or, yet again: mother and father have a procreative sexuality, whereas the child does not. This leads to the idea that the destruction of reality is equivalent to destruction of the paternal universe. Clinical case illustrations are provided, one of which centers on the assassination of an old man who, besides representing a paternal oedipal image, also represents reality itself. This case illustrates in concrete form the murder of the father, and hence of reality, accomplished by the pervert when he eradicates the paternal dimension of psychosexuality by regressing to the anal sadomasochistic dimension. PMID- 1856441 TI - Sadomasochism and the defense against recall of painful affect. AB - Defense against recall of painful affect is proposed as a significant element in the complex entity of neurotic sadomasochism and symptom formation. This formulation requires that the fantasy of reversibility--what happened can be undone--be analyzed in the transference and predict, for the patient, a painful feeling of loss and rage. The structure and tenacity of the powerful resistance to this work has the regressive, anal nature of reversibility which is also seen in the sadomasochistic characteristic of self and object interchangeability. The perceived threat of loss may be understood as related to early object loss, either whole or partial, and is associated with a flawed body image. Because the formative circumstances lie deep within the patient's past, reuniting residual affect, historical event, and early wishes by means of reconstruction is the only means of resolution. But, because it requires the relinquishment of the sustaining illusions of the sadomasochistic structure--omnipotentiality, omnipotence and bisexuality--the process will be experienced by the patient as intensely narcissistically dangerous. Vignettes from the analyses of two women illustrate the thesis and suggest the scope and direction of its clinical application. PMID- 1856442 TI - Sadomasochism in the psychoanalytic process, within and beyond the pleasure principle: discussion. PMID- 1856443 TI - The real person of the analyst and his role in the process of psychoanalytic cure. AB - This paper focuses on the real relationship with the analyst in the psychoanalytic situation as an aspect of the therapeutic process that leads to change. The role of free association, clarification, and interpretation of the transference are taken for granted as major activities of the analyst, and the real relationship with him is seen as a complementary but important ingredient for change. In particular, his emotional availability determines the climate of analysis. The concepts of neutrality, anonymity, and abstinence, though of importance as guideposts in the conduct of an analysis, have conceptual limitations that not infrequently bind the analyst in a stance that is not useful for the progress of the analysis. On occasion, confirmation by the analyst of the verity of an experience in the patient's early life facilitates the analytic process. This occurs particularly in situations of early trauma, but at times may include chronically traumatic early life experiences. An important motivating force in analysis is the patient's unconscious wish to find the ideal parent absent in early life experience, a wish that is experienced and ultimately analyzed. This is to be distinguished from a defensive idealized transference. Psychoanalytic developmental psychology contributes to our understanding of how the real person of the analyst, his emotional availability, his responsiveness at particular times, his attitude toward action and progressive change in the patient, affect the therapeutic process that leads to change. PMID- 1856444 TI - Beyond the what, when, and how of transference: a consideration of the why. AB - Transference has generally been discussed in terms of its operating to distort the way in which a current relationship is dealt with and experienced because of one's past. In the present paper, emphasis is placed on that aspect of transference which operates as a defense, and which is called into play in response to signal anxiety associated with a "pathogenic complex" and is based on (1) a traumatic experience of stimulus overload or (2) an intrapsychic conflict stemming from instinctual drive pressure which in turn threatens a repetition of the traumatic experience. Clinical illustrations are presented in which both traumatic experience and drive-conflict forces are prominent, leading to a discussion of the here-and-now versus reconstruction of the past, as well as affective/cognitive and interpersonal/intrapsychic factors. PMID- 1856445 TI - Freud and the figure of Moses: the Moses of Freud. AB - Moses was a lifelong preoccupation of Freud, representing a double and idealized self and object. Freud identified with different aspects of Moses during different periods of development, from concrete hero to abstract ideal. He turned to Moses in the concluding phase of his relationship with Fliess and his self analysis, and then at other times of crisis. The Moses recreated by Freud is important to the evolution of the concepts of the superego, and his Moses studies simultaneously illuminate the developmental significance of internalization, identification, and abstract symbolic thought. Latently autobiographical, the Moses motif is related to the analysis of unconscious conflict and trauma and to issues of Jewish identity and analytic ideals. PMID- 1856446 TI - On methods of reporting clinical material. AB - The members of the Committee on Scientific Activities of the American Psychoanalytic Association are concerned about the paucity of clinical data in psychoanalytic reports and by the quality of what does exist. We have proposed a few standards for clinical reports that we believe will be reliable and clear and will have enduring usefulness. We recognize the need for maintaining confidentiality and, at times, for disguise; we also recognize the need to balance these requirements against the dangers of misleading the reader (or listener). These conflicting requirements have resulted in our concentrating on some general principles for clinical reporting. We have appended a tentative form, and examples, to be considered for that purpose. PMID- 1856447 TI - Georg Groddeck's racism--a dismal discovery. PMID- 1856448 TI - A survey concerning the frequency of fantasies about the supervisor in candidate analysis. PMID- 1856449 TI - On Hispanic and Spanish as dream elements. PMID- 1856450 TI - The schema model. PMID- 1856451 TI - Presence of adenosine deaminase on the surface of mononuclear blood cells: immunochemical localization using light and electron microscopy. AB - Adenosine deaminase, which is essential for lymphoid differentiation and function, has previously been considered to be a cytosolic enzyme. In this report we demonstrate that it can be found associated with the plasma membrane of lymphocytes. By means of immunological techniques using both light and electron microscopy, adenosine deaminase was localized on the external side of the plasma membrane of normal lymphocytes and monocytes. Since the enzyme expression differed depending on the type of cell examined, new hypotheses about the mechanisms involving purine metabolism in immune dysfunctions or immunodeficiency syndromes may be considered. PMID- 1856452 TI - Ultrastructural distribution of myosin heavy chain mRNA in cardiac tissue: a comparison of frozen and LR White embedment. AB - Electron microscopy (EM) in situ hybridization provides the higher resolution necessary to determine the spatial relationship between a specific mRNA and the organelle containing the protein encoded by that message. EM in situ hybridization was used to determine the subcellular myosin heavy chain (MHC) mRNA distribution with respect to the myofibril in normal cardiac tissue. Sections of frozen or acrylic-embedded tissue were compared for ultrastructural integrity and content of endogenous mRNA. Papillary muscles dissected from hearts of normal rabbits were aldehyde-fixed and either frozen or embedded in LR White. EM in situ hybridization with no riboprobe, vector sequence, same-sense, and anti-sense biotinylated riboprobes was detected by indirect immunocytochemistry. Labeling density using an antisense probe was highest over the intermyofibrillar space, with an average signal five times that of background. Background labeling by nonspecific sense probe was consistently low but not random, also having the highest density of gold clusters over the intermyofibrillar space. Ultracryomicrotomy yielded a higher absolute number of gold clusters, but sections were fragmented and disrupted striated muscle morphology. LR White embedment maintained ultrastructural integrity but gave a lower absolute signal. Fortunately, MHC mRNA is an abundant message and can tolerate the decreased sensitivity of LR White. PMID- 1856453 TI - Ultrastructural localization of nuclear matrix proteins in HeLa cells using silver-enhanced ultra-small gold probes. AB - We describe a method for immunogold staining of nuclear matrix proteins using ultra-small gold particles. The nuclear matrix of HeLa cells is obtained by two fractionation steps: (a) cell permeabilization with Triton X-100 to isolate the cytoskeleton, and (b) nuclease digestion followed by an incubation in 0.25 M ammonium sulfate to isolate the nuclear matrix. To prevent redistribution of internal matrix proteins during nuclear matrix preparation, pre-fixation with 0.1% acrolein was performed. Under this condition up to 80% of protein and 90% of DNA and RNA could be removed on nuclear matrix isolation, without redistribution of internal nuclear matrix proteins. For immunogold labeling, 1-nm gold probes appeared to be required to obtain optimal penetration into the nucleus. These particles can be visualized after silver enhancement. After gold labeling the matrices are stained, embedded in Epon, and ultra-thin sections are prepared for examination in the electron microscope. The applicability of this method is examplified by the localization of a 125 KD internal nuclear matrix protein and the lamins A and C in nuclear matrix preparations of HeLa cells. PMID- 1856454 TI - Podocytes in glomerulus of rat kidney express a characteristic 44 KD protein. AB - We describe a new monoclonal antibody (MAb) directed against glomerular visceral epithelial cells (podocytes), generated by immunization with isolated rat kidney glomeruli. In immunoblotting experiments this MAb (IgG1 subclass) reacted with a 44 KD protein. In cryostat sections of normal rat kidney the MAb stained glomerular podocytes; therefore, we called the antigen pp44 (podocyte protein 44 KD). On 0.5-micron cryostat sections the signal could be more precisely ascribed to the podocyte foot processes, whereas the cell bodies appeared virtually unreactive. On ultra-thin frozen sections pp44 was found within the cytoplasm of podocyte foot processes at their origin from their parent processes. The podocyte cell membrane was not labeled. All other parts of the nephron were unreactive. An additional but weaker immunoreaction was found in the arterial endothelium; the endothelia of other vessels (peritubular capillaries, veins) were negative. In human kidney anti-pp44 revealed the same staining pattern as in rat kidney. The expression of pp44 was also studied in newborn rat kidney. The early stages of glomerular development (renal vesicle, S-shaped body) were negative. pp44 first appeared during the capillary loop stage, i.e., when formation of podocyte foot processes commences. In comparing the present results with published data, pp44 is clearly different from other antigens thus far described in podocytes. From the results of this investigation we conclude that pp44 represents a novel cytoplasmic protein of podocytes. Our data suggest a cytoskeletal role for pp44 in preserving the complex architecture of podocytes. This idea is confirmed by the simultaneous appearance of foot processes and anti-pp44 immunoreactivity during glomerular development. PMID- 1856455 TI - Protein AG-gold complex: an alternative probe in immunocytochemistry. AB - The purpose of this study was to evaluate the use of protein AG tagged with colloidal gold as a reliable immunocytochemical reagent. Protein AG is a recombinant of 47.3 KD molecular weight and pI = 4.3, which displays immunoglobulin Fc binding sites for both staphylococcal protein A and streptococcal protein G. It adsorbs to 10-nm colloidal gold particles with a lower affinity than does protein A, and is saturable. A maximal number of 12 protein AG molecules could be accommodated on the gold particle surface. Protein AG-gold conjugates yielded positive signals in post-embedding immunocytochemical assays when used as a secondary reagent in conjunction with several species and classes of polyclonal (rabbit, goat, sheep, guinea pig) and mouse monoclonal immunoglobulins (IgG1, IgG2, and IgG3). In addition, protein AG-gold was found to be a useful reagent in immunoblot analysis because of its ability to bind and identify nitrocellulose-immobilized IgGs (rabbit, mouse, goat, sheep, rat, and cow). Its spectrum of specificity towards various types of antibodies combines those of the parental protein A and protein G molecules. The protein AG-gold complex therefore appears to be a highly versatile and convenient alternative probe for immunochemical and immunocytochemical studies. PMID- 1856456 TI - Changes in cell polarity during mitosis in rat parotid acinar cells. AB - We studied the ultrastructure and cytochemistry of mitotic parotid acinar cells in vivo after induction of mitosis by isoproterenol injection. With entrance of the cells into the division cycle, the Golgi apparatus lost its characteristic stacked structure and internal polarity among the cisternae, appearing as fragments distributed throughout the cytoplasm. These fragments consisted of electron-lucent vesiculotubular structures and electron-dense 70-nm vesicles; neither component showed thiamine pyrophosphatase activity, a marker for trans cisternae of the Golgi apparatus, but the 70-nm vesicles showed a positive reaction for osmium impregnation, indicating retention of the cis nature. The rough endoplasmic reticulum was dilated and fragmented. Recovery of the structure of Golgi apparatus and rearrangement of rough endoplasmic reticulum occurred in daughter cells during telophase. These changes were the same as those observed after drug-induced inhibition of protein transport. The secretory granules were not dispersed but were divided into two groups with which centrioles were closely associated. Both groups migrated with the centrioles as far as the next interphase. The distribution of 5'-nucleotidase on the luminal plasma membrane showed no change during the process of division, thus demonstrating that surface polarity was maintained during mitosis. These changes in organelle structure and distribution may be due to the conversion of cell function from a secretory to a mitotic action. PMID- 1856457 TI - Different immunoelectron microscopic locations of progesterone receptor and HSP90 in chick oviduct epithelial cells. AB - The intracellular locations of the components of the heterooligomeric progesterone receptor (PR), heat-shock protein (hsp90), and the ligand-binding component were studied by immunoelectron microscopy in the chick oviduct, using immunogold double labeling and peroxidase techniques with monoclonal antibodies (MAb) against hsp90 (7D alpha and 4F3) and against PR (PR6 and PR13). PR was located in the nuclei of epithelial cells independently of the presence or absence of ligand. Cells with apically located nuclei were often PR negative. Ten minutes after progesterone administration no apparent change was seen in PR immunoreactivity, but chromatin underwent extensive rearrangement and PR was seen at the margins of the hetero- and euchromatin. The nucleoli did not contain PR. Hsp90 was located in the cytoplasm as aggregates, often inside small vesicles. In the apical part of the cell, hsp90 was located at the Golgi complex. The nuclei contained no detectable amounts of hsp90 except for that in the nucleoli. Ten minutes after progesterone administration the location or immunoreactivity of hsp90 did not alter. Thus, there seems to be a clear difference in the intracellular distribution of PR and hsp90. The epithelium also exhibited some cells with high levels of hsp90 and no or low levels of PR. These results raise the question of whether PR is associated with hsp90 in intact cells. PMID- 1856458 TI - Differentiation-dependent expression of lectin binding sites on normal and neoplastic keratinocytes in vivo and in vitro. AB - We used lectins as probes to demonstrate the composition of membrane carbohydrates of canine keratinocytes in various functional stages and various degrees of differentiation. Keratinocytes during normal epidermal turnover were compared by lectin immunohistochemistry to cells of hyperplastic epidermis and neoplastic keratinocytes. Three types of epidermal tumors and oral squamous cell carcinomas were examined. In addition, two in vitro tissue culture systems for keratinocytes were studied and compared with in vivo epithelium. In normal skin, PNA reacted only weakly with basal cells, whereas in hyperplastic skin basal cells bound this lectin strongly, demonstrating increasing expression of PNA binding sites with increasing thickness of the stratified squamous epithelium. ConA bound to basal cell tumors only. In oral squamous cell carcinomas, the expression of distinct lectin binding sites correlated with certain histological growth patterns, e.g., UEA-I reacted with highly invasive tumors but not with tumors showing a solid growth pattern. Using cell surface iodination and polyacrylamide gel electrophoresis, distinct differences in cell membrane protein expression were demonstrated between normal and neoplastic keratinocytes. SDS polyacrylamide gel electrophoresis of cultured normal and neoplastic keratinocytes revealed several cell surface proteins that are specific for either cell type. Neoplastic cells specifically express a 140 KD lectin binding cell surface glycoprotein. The results of this study show that lectin binding patterns of keratinocytes are dependent on the functional state and the degree of differentiation of the cells and demonstrate correlation of some histological growth patterns with distinct lectin binding phenotypes, suggesting association of expression of cell membrane carbohydrate moieties with growth patterns. In addition, close similarities between "lifted cultures" grown at the air-liquid interface and native tissue demonstrate the value of this culture system as a model for differentiated stratified squamous epithelium. PMID- 1856459 TI - Microquantitative analysis of the intra-acinar profiles of glutamate dehydrogenase in rat liver. AB - In adult male and female rat liver, the activity of NAD(+)-and NADP(+)-dependent glutamate dehydrogenase (GDH) was microquantitatively measured in tissue samples of 50-150 ng, microdissected continuously along the sinusoidal length. Total activity of GDH with NAD+ as co-factor was found to be higher by a ratio of about 1:2.3 than with NADP+. All intra-acinar enzyme profiles, irrespective of sex, showed an increasing gradient of GDH activity from the periportal beginning to the perivenous end. These findings are at variance with the immunohistochemical localization of GDH in rat liver. The microquantitative GDH profiles with higher perivenous values could indicate a more pronounced glutamine synthesis in Zone 3 of the liver acinus. PMID- 1856460 TI - Measurement of proliferation nuclear and membrane markers in tumor cells by flow cytometry. AB - Nuclear and membrane markers that have been related to proliferative activity were measured by flow cytometry. The markers studied were transferrin receptor (TR), Ki-67 antigen, and epidermal growth factor receptor (EGFR). Two-color analysis for DNA via propidium iodide binding and for antigen expression via either a direct or indirect immunofluorescence assay was performed on three different cell lines and a solid human tumor model. The three cell lines tested were MCF-7 (breast), K-562 (leukemia), and A431 (a squamous cell). The solid tumor was obtained by subcutaneous injection of A431 cells into an athymic nude mouse. Our results demonstrate that TR are cell-cycle specific and can be readily measured in the cell lines. Ki-67 antigen is also cell-cycle specific in the cell lines tested, but the mean channel specific fluorescence uptake varies in the cell types. Finally, the EGFR was observed only in the A431 cell line, with most cells equally expressing this receptor. A bimodal distribution of EGFR was observed in A431 cells obtained from a solid tumor grown in an athymic nude mouse system. This suggests that cell line analysis may not always represent what might be observed under in vivo conditions. There are advantages to flow cytometry measurements of these factors which might be useful in predicting how patients should be treated and possibly the prognosis of cancer patients. PMID- 1856461 TI - Localization of hyaluronan in regions of the human female reproductive tract. AB - Accumulation of hyaluronan has previously been observed in various organs as an inflammatory response. To study the presumed connection between infertility due to a tubal factor and inflammation, we performed an analysis of the hyaluronan distribution in biopsy specimens from the female reproductive tract, using a biotinylated hyaluronan binding protein (HABP) as a histochemical probe. In normal specimens hyaluronan was localized in the dense, irregular connective tissue surrounding blood vessels of various sizes. Smooth muscle and columnar epithelium were devoid of hyaluronan. The isthmic part of the normal Fallopian tube showed moderately intense staining of the entire lamina propria, whereas normal fimbriae stained weakly. No cyclic changes in hyaluronan content were observed. In biopsy specimens from women with infertility due to a tubal factor, intense staining, stronger than in normal tubes, was detected in the adhesions and in the lamina propria of sactosalpinx. This may indicate that infertility due to a tubal factor is associated with an ongoing inflammatory and/or proliferative process. PMID- 1856462 TI - Generation of monoclonal antibodies directed against organ-specific endothelial cell surface determinants. AB - Organ-specific determinants expressed on the luminal surface of vascular endothelia are often unstable when cells are removed from their normal tissue environment and grown in culture. Unspecific endothelial cells of large vessel origin [e.g., bovine aorta (BAEC)] can be modulated to express and preserve such determinants when they are grown on the extracellular matrix of the desired organ. Lung matrix-modulated BAEC were used here to generate MAb against lung specific vascular endothelia. Immunization was accomplished with outside-out membrane vesicles obtained by incubating BAEC monolayers grown on lung matrix with a low-strength paraformaldehyde solution. In four of the six fusions performed, this active immunization was preceded by passive immunization with mouse antiserum directed against membrane vesicles from BAEC grown on plastic. Among the growing hybrids, 7.6% secreted MAb that bound efficiently to both BAEC grown on lung-derived matrix and BAEC grown on plastic, while 3.5% (50) secreted MAb that bound primarily to BAEC grown on lung matrix. The fusion data show that only a passive/active immunization protocol yielded MAb directed against lung specific endothelia. For example, MAb 6D3 and 5F5 selectively recognized endothelia from small- and medium-sized venules of bovine lungs, but failed to react with endothelial cells in other organs and tissues. PMID- 1856463 TI - Gay people, sex and the media. PMID- 1856464 TI - Sex and genre on prime time. AB - Sexual activity is never explicitly represented on network television programs. Rather, realms of sexuality are suggested. These realms are represented differently according to the genre of the program; sitcoms explore the realm of the taboo, while nighttime soaps plumb the inevitable consequences of sexual activity. Detective shows display the sexual underworld. When a program shows sexuality from more than a generic perspective, it provides a more global representation and is also a more fruitful object of study. PMID- 1856465 TI - Dr. Ruth Westheimer: upsetting the normalcy of the late-night talk show. AB - For the most part, the late-night talk/variety television genre has been analyzed as little more than a promotional device for producers of popular culture products. Using concepts of dialogic discourse borrowed from M.M. Bakhtin and of star discourse theorized by Jimmie Reeves, this paper explores the ideological complexity available in the content of late-night programming. The various inflections of Dr. Ruth Westheimer within the broadcast context of the late-night talk/variety genre provide the focus of this analysis. PMID- 1856466 TI - Of mice and men: an introduction to mouseology or, anal eroticism and Disney. AB - This essay deals with two important comics, Walt Disney's Mickey Mouse and George Herriman's Krazy Kat, and considers the social, cultural, psychological and symbolic significance of the main characters and their creators. In the discussion of Disney and his work (based, in part on writings about him) it is suggested that he exhibited traits associated with anal eroticism, which raises an interesting question about the popularity of his work with the American public. The two dominant themes found in Krazy Kat are described as "the triumph of illusion over reality" and "anti-authoritarianism." In a comparison of the two characters, it is shown they are polar opposites: Mickey Mouse is sadistic, asexual, and anal while Ignatz Mouse, the hero of Krazy Kat, is playful, sexual, and phallic. PMID- 1856467 TI - The magazine of a sadomasochism club: the tie that binds. AB - The monthly magazine of a sadomasochism club was investigated as a means of describing important issues for club members. The magazine was selected for this exploratory study because it is: (a) The club's only recorded history; (b) the only repository of club members' writings and photographs; and (c) the only link to the club for about 15% of the membership who do not attend meetings or other club activities because they reside some distance from the club's two West Coast chapters. A descriptive content analysis was performed on 47 issues of the club's magazine, published between October 1983 and January 1988, and the results were combined with the findings of a December 1987 magazine readership survey completed by 44% of the 812 dues-paying club members. The author's nonparticipant observations of club programs are also reported. The results indicate the magazine's space is filled by seven subject categories: S/M media reviews (2% of space), S/M poetry (5%), S/M issues (10%), S/M "how-to" (12%), S/M photography (14%), fantasy and real S/M stories (17%), and organizational reports (40%). PMID- 1856468 TI - Out of the mainstream: sexual minorities and the mass media. AB - In a society dominated by centralized sources of information and imagery, in which economic imperatives and pervasive sources of values promote the search for large, common-denominator audiences, it is useful to look at the fate of those who, for one reason or another, find themselves outside of the mainstream. This paper addresses the general questions of minority perspectives in the context of the study of mass media content and effects. More specific attention is paid to the situation of lesbian women and gay men as members of the mass media audience. PMID- 1856469 TI - Lesbian and gay rights as a free speech issue: a review of relevant caselaw. AB - The legal struggles waged by lesbian and gay male litigants almost invariably involve issues of freedom of expression, broadly construed. To illustrate this point, a wide array of caselaw is examined--ranging from classic "access to a forum" controversies to those concerning symbolic conduct and freedom of association (including marriage and child custody law), employment discrimination, and proscriptions against deviant sexual conduct. In each category, claims to a right of freedom of expression are manifested. Cautionary notes are offered concerning those cases in which gay litigants try to protect their rights by inhibiting the speech of others. A brief concluding section assesses the long-term and short-term efficacy of raising First Amendment arguments (as opposed to privacy or equal protection arguments) in lesbian/gay male litigation. PMID- 1856470 TI - Gays, lesbians, and the media: a selected bibliography. AB - The focus of this selected bibliography is on print, aural, and visual resources dealing with gay males, lesbians, and the mass media. Listings were selected on the basis of their perceived value to scholarly researchers and interested members of the more general public. Individual news stories, reviews of specific films or television programs, and coverage of gay males and lesbians in the theatre and arts are not included. While references to popular music were sought, only a few items were located and are included. There were two major obstacles confronted when compiling this bibliography. First, much of the media of the gay and lesbian communities in the United States is not indexed. Second, very few libraries subscribe to many of the more popular and important print resources (e.g., Advocate, Gay Community News) on the topics of focus. Even more inaccessible are regional publications and literature that focus on erotica but often include valuable items on the gay and lesbian communities as well. PMID- 1856471 TI - Sensationalism or sensitivity: use of words in stories on acquired immune deficiency syndrome (AIDS) by Associated Press Videotext. AB - Although it appeared initially reluctant to cover the story at all, the mainstream press in the United States has supplied almost daily reports on AIDS since the mid-1980s. The author examined four weeks of stories on the Associated Press Videotext service in early 1986 in an effort to evaluate the validity of critics' charges that journalists were over-emphasizing the role of homosexuals in the progress of the disease, and that their stories were laden with negative or sensationalistic terms. The author found little evidence from the words used in the stories of distortion in telling the AIDS story, but speculated that such distortion might be found in selection, editing, and presentation decisions made by gatekeepers. PMID- 1856472 TI - The important role of mass media in the diffusion of accurate information about AIDS. AB - This paper explores the vital role of mass media in diminishing the lack of consensus among those at risk for AIDS and those who treat them. It examines the perceptions of these groups with regard to the seriousness of the AIDS threat, what people at risk are really doing to protect themselves and others, and the accuracy and objectivity of media reports about AIDS. Results indicate that there is a disarming lack of consensus among those people who can do the most to influence the spread of AIDS. Results also indicate that those people at greatest risk for AIDS and for spreading the disease distrust the accuracy and objectivity of the media. The authors argue that consensus is required for a concerted fight on AIDS and that the mass media offer an effective avenue for encouraging it. They also explore methods for regaining media respect among high risk groups with regard to AIDS reporting. PMID- 1856473 TI - Introduction: the body electric--human sexuality and mass media. PMID- 1856474 TI - Television viewing and adolescents' sexual behavior. AB - Over the past two decades the sexual content on television has increased in frequency and explicitness but has seldom included depiction of the use of contraceptives. Concurrently, the age of initiation of heterosexual intercourse has decreased and the number of teenaged pregnancies has remained high. Are these trends related? This survey of 391 adolescents found that those who chose heavier diets of sexy television shows were more likely than those who viewed a smaller proportion of sexual content on television to have had sexual intercourse. This relationship held regardless of perceived peer encouragement to engage in sex and across race and gender groups. While causal direction is not clear from these data, the relationship suggests that either sexual activity results in increased interest in sexual content in the media and/or that viewing such content leads to sexual activity. In either case, the finding points to the need for further research and increased discussion and portrayal of the use of contraceptives on television. PMID- 1856475 TI - Television viewing and early initiation of sexual intercourse: is there a link? AB - Using data from the National Survey of Children, this paper examines the hypothesis that the amount of time children spend viewing television and the extent to which the content viewed is sexual in nature is related to the initiation of sexual activity. Several theories that would lead to this hypothesis are reviewed. The data do not provide any strong or consistent evidence for such links. However, some aspects of the context in which television is viewed are related to sexual activity. The authors suggest ways in which the design and measures could be strengthened to provide a more rigorous test of the hypothesis. PMID- 1856476 TI - Application of hepatitis B virus (HBV) DNA sequence polymorphisms to the study of HBV transmission. AB - Short sequences in hypervariable regions of the hepatitis B virus (HBV) genome can be used to identify different strains, providing a novel approach to the study of HBV transmission. The nucleotide sequence in positions 2551-2650 (1:EcoRI site) was determined for serum HBV DNA from 96 Chinese children living in Hong Kong and from 38 of their parents. HBV DNA was extracted and sequenced after amplification with the polymerase chain reaction, using as primers oligonucleotides corresponding to two conserved sequences. Among 82 unrelated children, 32 HBV DNA variants were present. One sequence was present in 33 children and 31 variants were found among the other 49. Siblings within each of nine families had the same variant; in three families siblings had different variants. Six of the eight fathers and 28 of the 30 mothers had HBV DNA sequences identical to those of their offspring. A total of 34 variants were found among the 134 individuals. The hypothesis of random assortment of sequences in parents and children was rejected (P less than .00005). Thus, this new approach proves the occurrence of intrafamilial transmission of HBV among Chinese. PMID- 1856477 TI - Development of cross-reactive antibodies to plasminogen during the immune response to dengue virus infection. AB - The four serotypes of dengue virus (a mosquito-borne flavivirus) cause an acute febrile illness (dengue fever) or a more prolonged illness with plasma leakage resulting in hypovolemia (dengue hemorrhagic fever). Hemorrhage may accompany either. Epidemiologic data suggest a role for dengue antibodies in pathogenesis. Computer analysis revealed a 20-residue region of similarity in amino acid sequence between the dengue type 4 envelope glycoprotein (E) and a family of clotting factors, including plasminogen, the prime mediator of fibrinolysis. By use of synthetic peptides in ELISA, E antibodies that potentially bind plasminogen were detected in 75% of 40 Thai patients acutely infected with dengue virus type 1, 2, 3, or 4. Plasminogen cross-reactivity of dengue antibodies was shown to be specific for the related sites in E and plasminogen. The dengue E sequence with similarity to plasminogen is largely conserved within the currently known flavivirus E sequences. However, 15 Thai patients hospitalized for illness caused by Japanese encephalitis virus (a flavivirus not associated with hemorrhage) did not develop plasminogen-cross-reactive antibodies, and this finding correlated with failure of Japanese encephalitis virus antibodies to bind to the plasminogen-cross-reactive site in E. PMID- 1856479 TI - Variability of penicillin-binding proteins from penicillin-sensitive Streptococcus pneumoniae. AB - Penicillin-binding proteins (PBPs) from penicillin-susceptible strains of Streptococcus pneumoniae are believed to be fairly similar in contrast to PBPs occurring in resistant isolates. The antigenic variation of PBPs 1a and 2b in 65 penicillin-susceptible strains from different geographic areas and a wide variety of isolation sites was analyzed using a set of specific antisera and monoclonal antibodies. Three strains contained different antigenic variants of PBP 1a, and 50 strains contained one of three antigenic variants found in PBP 2b. Seven patterns of antibody reactivity could be defined; all but one were distinct from those found recently in resistant strains. In addition, electrophoretic mobilities of all six PBPs, compared after conventional SDS-PAGE and fluorography, revealed an unexpected variation of PBP-profiles even for strains of one sero-group. Few strains appeared identical to each other or to the laboratory reference strain R6. PMID- 1856478 TI - Intercontinental spread of a multiresistant clone of serotype 23F Streptococcus pneumoniae. AB - Isolates of serotype 23F Streptococcus pneumoniae with high levels of resistance of penicillin have been commonly recovered in Spain for more than a decade. Recently penicillin-resistant serotype 23F S. pneumoniae strains were also isolated from children attending a day-care center in Cleveland. A number of Spanish and Cleveland isolates were compared by electrophoretic analysis of penicillin-binding protein (PBP) profiles and DNA restriction endonuclease cleavage profiles of the PBP 2X and 2B genes amplified with the polymerase chain reaction and by multilocus enzyme electrophoresis. All strains were identical by these criteria. The findings demonstrate that the Spanish and Cleveland isolates are clonally related and suggest that this antibiotic resistant clone of serotype 23F S. pneumoniae has spread intercontinentally from Spain to the United States. PMID- 1856480 TI - Antigenic variation of penicillin-binding proteins from penicillin-resistant clinical strains of Streptococcus pneumoniae. AB - Penicillin-resistant strains of Streptococcus pneumoniae that are isolated with increasing frequency worldwide contain low-affinity penicillin-binding proteins (PBPs). The relatedness of PBPs from 55 resistant strains isolated on three continents was investigated by testing the reactivity of antibodies specific for PBP 1a or 2b and by comparing the PBP patterns. Seventeen patterns of antibody reactivity could be distinguished, 12 of which were specific to one isolate. Most strains, including all German and South African strains, had a unique PBP profile. A few groups of Spanish and Finnish isolates were identified where the strains within each group shared the same PBP profile, the same antigenic variants of PBPs 1a and 2b, and the same serogroup, suggesting that they represent different clones of S. pneumoniae. The results demonstrated highly variable pathways of resistance development and confirmed that resistant strains have emerged independently in different locations. PMID- 1856481 TI - Pathophysiology and histopathology of group B streptococcal sepsis in Macaca nemestrina primates induced after intraamniotic inoculation: evidence for bacterial cellular invasion. AB - Four pregnant Macaca nemestrina dams at 140-145 days of gestation received an intraamniotic inoculation of group B streptococci (GBS). All four premature infants were born by cesarean delivery, were bacteremic at birth, and showed symptoms of GBS sepsis similar to infected human infants with early-onset disease. Three infants did not receive antibiotics and died of GBS sepsis by 10 h of age despite mechanical ventilation and fluids for blood pressure support. Penicillin treatment of the fourth infant prolonged survival and decreased the requirement for supportive therapy. Quantitative cultures and histopathology were done on all four infants. Transmission electron microscopy of lung tissue demonstrated GBS within membrane-bound vacuoles of type I and II alveolar epithelium and interstitial fibroblasts. This model should be useful for studying the early steps in the pathogenesis of early-onset GBS infections. GBS may enter alveolar epithelial cells to transit this barrier and ultimately disseminate via the blood-stream. PMID- 1856482 TI - Enteropathogens associated with acute diarrheal disease in urban infants in Sao Paulo, Brazil. AB - To determine the prevalence and epidemiology of enteropathogens in acute infantile diarrhea, 500 infants less than or equal to 12 months of age with diarrhea and 500 age-matched control subjects coming to a Sao Paulo emergency room were studied. Enteropathogens were identified in 55% of case infants and 10% of controls; enteropathogenic Escherichia coli (EPEC) of classic EPEC serotypes producing EPEC adherence factor (EAF) (26% of case infants), rotavirus (14%), Salmonella species (8%), enterotoxigenic E. coli (7%), and Shigella species (5%) were associated with diarrhea. Isolation of EAF+ classic EPEC decreased with increasing age of cases and peaked in spring, whereas rotavirus was least common in early infancy and peaked in fall and winter. Bloody stool had a 36% positive predictive value for Shigella infection, EAF+ classic EPEC were highly resistant to antimicrobial drugs. Among poor Sao Paulo infants, EAF+ classic EPEC equaled or exceeded rotavirus throughout the year as a cause of diarrhea bringing children to medical attention. PMID- 1856483 TI - An outbreak of Escherichia coli O157:H7 colitis associated with consumption of precooked meat patties. AB - An outbreak of Escherichia coli O157:H7 hemorrhagic colitis at a Minnesota junior high school in October 1988 comprised 32 cases among 1562 students (attack rate, 2.0%). Four children were hospitalized; none developed hemolytic-uremic syndrome. Case children were more likely than controls to have eaten heat-processed meat patties (odds ratio, 6.2; 95% confidence interval, 2.0-20.1; P less than .001) in the school cafeteria on a specific day. The minimum estimated attack rate among students who ate these patties was 8%. The patties should have been sufficiently cooked by the manufacturer to destroy enteric pathogens before they were frozen and distributed. E. coli were cultured from frozen patties that were manufactured at the same plant on the same dates as the implicated patties, but serotype O157:H7 was not isolated. Heat-processed meat patties may serve as vehicles for E. coli O157:H7 infection, and currently there are no federal or state regulatory standards to ensure the safety of these products. PMID- 1856484 TI - Detection of experimental Haemophilus influenzae type b bacteremia and endotoxemia by means of an immunolimulus assay. AB - The rapid quantitation of bacteria in blood was achieved by using a novel assay method for gram-negative bacterial lipopolysaccharide (endotoxin, LPS). The assay involves the capture of specific LPS onto microtiter plates by means of monoclonal antibodies directed against the oligosaccharide region of the LPS, followed by detection of the bound LPS by a chromogenic Limulus amebocyte lysate (LAL) system. This immunolimulus (IML) assay combines the specificity of monoclonal antibodies with the sensitivity of the LAL system to achieve the first specific, sensitive quantitation of bioactive endotoxin in plasma. In the animal model tested, Haemophilus influenzae type b (Hib) bacteremia in infant rats, there was a strong correlation between IML results and the concentration of Hib colony-forming units in blood samples (r = .845, P less than .001). Using antibodies with appropriate specificities, this approach should be useful for rapid detection of a wide range of gram-negative bacteria and endotoxins in blood. PMID- 1856485 TI - A temperature-dependent rabbit model for production of dermal lesions by Haemophilus ducreyi. AB - The fact that optimal in vitro growth of Haemophilus ducreyi occurs at 33 degrees C prompted evaluation of the effect of temperature on the ability of this organism to produce skin lesions in rabbits after intradermal inoculation. Animals housed at a reduced ambient temperature (15-17 degrees C) consistently developed necrotic lesions when injected intradermally with 10(5) cfu of H. ducreyi; this inoculum did not produce necrotic lesions in animals housed at normal room temperature (23-25 degrees C). Lesion production in this new model was dependent on both viability of the H. ducreyi inoculum and replication of these organisms after intradermal injection. Histopathologic examination of the lesions revealed that H. ducreyi infection of the rabbit dermis evolves from an acute inflammatory reaction to abscess formation. Evaluation of three additional strains of H. ducreyi in this model confirmed that lesion formation was not bacterial strain-dependent. This new temperature-dependent rabbit model for productive H. ducreyi infection will facilitate investigation of the molecular pathogenesis of chancroid. PMID- 1856486 TI - Characteristics of experimental Candida albicans infection of the central nervous system in rabbits. AB - Different concentrations (10(7), 10(5), 10(3) cfu/ml) of Candida albicans were injected intracisternally in rabbits. The highest inoculum was fatal within 14 h in all animals. In recipients of 10(5) and 10(3) cfu/ml inocula, the mean +/- SD peak cerebrospinal fluid (CSF) tumor necrosis factor-alpha (TNF alpha) concentrations were 1.6 +/- 2.42 and 0.3 +/- 0.59 ng/ml, respectively, at 6 h; the mean +/- SD CSF leukocyte and protein concentrations were 6291 +/- 6515 and 453 +/- 674 cells/mm3 (at 24 h) and 118 +/- 90 and 109 +/- 122 mg/dl (at 12 and 24 h), respectively. At 6-10 days after inoculation, a second peak of TNF alpha activity was accompanied by increased CSF inflammation. Mortality in the 10(5) and 10(3) cfu/ml inoculum groups was 56% and 22%, respectively. Fatal infection was associated with higher second CSF peak TNF alpha and leukocyte concentrations and a larger proportion of culture-positive CSF samples. Histopathology revealed hyphal invasion, vasculitis, abscesses, and acute and chronic inflammatory infiltration of meninges and brain parenchyma. This model can be useful for evaluation of the pathogenesis and therapy of central nervous system fungal infections. PMID- 1856487 TI - Modified Western blot assay for confirmation and differentiation of human T cell lymphotropic virus types I and II. AB - Disease association studies of human T cell lymphotropic virus (HTLV) types I and II are hindered by the need for multiple assays to confirm and differentiate between the viruses. A modified Western blot assay has been developed using HTLV I viral lysate and unique (MTA-4) and shared (p21E) HTLV recombinant proteins. By defining confirmation of infection as the presence of antibodies to p24 gag protein and to p21E, all 56 HTLV-I and 49 HTLV-II antisera were confirmed by this modified Western blot alone. Differentiation was determined by reactivity to MTA 4. All HTLV-I antisera reacted with MTA-4 and all HTLV-II antisera did not react with MTA-4. These findings indicate the utility of selected HTLV-I recombinant proteins in a single assay format to confirm and differentiate infections with HTLV-I and HTLV-II. PMID- 1856488 TI - Antibody responses after immunization with killed oral cholera vaccines during the 1985 vaccine field trial in Bangladesh. AB - Sera collected during the 1985 oral cholera vaccine trial in Matlab, Bangladesh, which demonstrated efficacy of a whole cell combined with cholera B subunit vaccine (WC/BS) and a whole cell only vaccine (WC), were analyzed for antitoxin and vibriocidal antibodies. Before vaccines were given, antitoxin titers were highest in children, especially those with O blood group, whereas vibriocidal titers rose throughout life. Two weeks after three doses of vaccine, geometric mean antitoxin titers were 2.5-4.5 times higher in vaccinees who received the WC/BS vaccine; the vibriocidal titers were 1.3-2.1 times higher in vaccinees who received either vaccine. The titer elevations were relatively brief and were barely detectable 7 months after the third dose even though significant levels of protection persisted greater than or equal to 3 years. Thus, the oral vaccines induced a serum response in this large field trial that was similar to that seen in earlier pilot studies, but the duration of the serum responses was much shorter than the duration of the protection. PMID- 1856489 TI - Culture-confirmed pneumonia due to Chlamydia pneumoniae. AB - Diagnosis of infection caused by Chlamydia pneumoniae, a newly recognized respiratory pathogen, has proved difficult. Between July 1987 and April 1988, culture and serologic tests for C. pneumoniae were done on specimens from 49 patients with pneumonia seen at an Atlanta hospital emergency room. Cultures from 3 patients (6%) grew C. pneumoniae. Genus-specific Chlamydia complement fixation titers and microimmunofluorescence titers for C. pneumoniae were suggestive of acute infection in all 3 culture-positive patients. Three other patients had evidence of acute disease by published criteria for antibody titers. Most studies of C. pneumonia have not had culture-proven cases; the 6% rate of positive cultures in this study support the role of C. pneumoniae as a cause of pneumonia. More widespread availability of simplified culture systems for C. pneumoniae is needed. Caution should be used when interpreting serologic tests in the absence of culture confirmation. PMID- 1856490 TI - Quantitative culture of bronchoalveolar lavage from patients with anaerobic lung abscesses. AB - The study of anaerobic infections of the lung is usually limited to the use of invasive techniques such as transtracheal aspiration (TTA) to avoid contamination by oral flora. Bronchoalveolar lavage (BAL) has been used successfully in the study of the etiology of pneumonia in immunocompromised patients. This study evaluated the role of the quantitative culture of BAL in the diagnosis of lung abscess. Four episodes of lung abscess in three patients were studied, and the results of quantitative culture of BAL were compared with those of the standard technique of TTA. Nineteen anaerobic bacterial species were recovered from the BAL fluid, all but one at concentrations greater than 10(3) cfu/ml. Culture of BAL fluid yielded 18 of 22 of the isolates cultured from TTA, including 12 of 16 of the anaerobic bacteria. This study suggests that quantitative culture of BAL fluid may be useful in the bronchoscopic evaluation of lung abscess. PMID- 1856491 TI - Comparative safety, tolerance, and pharmacokinetics of amphotericin B lipid complex and amphotericin B desoxycholate in healthy male volunteers. AB - Amphotericin B lipid complex (ABLC), a lipid complex formulation of amphotericin B, and amphotericin B desoxycholate (AB) were compared for safety, tolerance, and pharmacokinetics in two groups of eight healthy male volunteers. After a 1-mg test dose, study drug was infused at 0.1, 0.25, and 0.5 mg/kg; the 0.5-mg/kg dose was not given to subjects receiving AB. ABLC caused few acute adverse effects except for mild somnolence (drowsiness) in six volunteers. In addition, three of eight ABLC recipient had asymptomatic, transient serum transaminase elevations that resolved spontaneously. The AB recipients experienced more acute side effects, but only one had a mild shaking chill: three of eight also experienced sleepiness. No significant changes in vital signs, electrocardiogram, oximetry, pulmonary function, or clinical status were observed in either group. Due to its increased estimate volume of distribution and estimated clearance. ABLC yielded decreased amphotericin B levels and area under the serum concentration versus time curve relative to AB. PMID- 1856492 TI - Diagnosis of human African trypanosomiasis and visceral leishmaniasis based on the detection of anti-parasite-enzyme antibodies. AB - A sensitive diagnostic assay for parasitic infections based on the detection of anti-enzyme antibodies is presented. All serum antibodies produced in response to parasite antigens are immobilized via their Fc domain on matrix-bound protein G. Incubation of the immobilized antibodies with saturating amounts of parasite extract results in the binding of all recognized antigens, including those directed against a specific and readily measurable enzyme. The amount of bound enzyme is proportional to the anti-enzyme antibody concentration in the serum. The application of this principle is demonstrated for the diagnosis of both human African trypanosomiasis and visceral leishmaniasis by the detection of antibodies against parasite acid phosphatases. PMID- 1856493 TI - Herpes simplex encephalitis: the case against brain biopsy. PMID- 1856494 TI - Elevated serum interleukin-2 receptors in a newly identified group with high rates of human T cell leukemia virus type I infection in Israel. PMID- 1856495 TI - Disseminated mixed Mycobacterium simiae-Mycobacterium avium complex infection in acquired immunodeficiency syndrome. PMID- 1856496 TI - Randomized trial of 5-day rifampin versus 1-day doxycycline therapy for Mediterranean spotted fever. PMID- 1856497 TI - Transient acquired factor II deficiency with Mycoplasma pneumoniae infection. PMID- 1856499 TI - Evidence of coccidioidomycosis in the skeleton of an ancient Arizona Indian. PMID- 1856498 TI - Persistence of Cryptococcus neoformans in the prostate: failure of fluconazole despite high doses. PMID- 1856500 TI - Stabilization of drug resistance (chloroquine and amodiaquine) of Plasmodium falciparum in semiimmune populations in the Congo. PMID- 1856501 TI - Adult human toxocariasis acquired by eating raw snails. PMID- 1856502 TI - Privacy (or liberty) and assisted suicide. AB - There is renewed professional and popular interest in the questions surrounding the legality of assisted suicide. With the U.S. Supreme Court's decision in the Cruzan case, the legal questions will be determined by state courts and legislatures. This article examines the arguments underlying the claim for legalization of assisted suicide. Although it appears to come within the confines of privacy, assisted suicide constitutes a more radical change in the law than its proponents suggest. Assisted suicide in the context of its own complexities and other problems facing society, represents a dubious advance in patient rights or social justice. PMID- 1856503 TI - The relationship of pain and symptom management to patient requests for physician assisted suicide. AB - Uncontrolled pain and multiple adverse symptoms compel some cancer patients with advanced disease to consider suicide or to request physician-assisted suicide as their only option. Any debate that focuses on the options to terminate life in patients with advanced disease must give adequate consideration to the existing level of care for patients with these distressing symptoms. Numerous studies have described the educational, attitudinal, and legislative barriers that exist and prevent patients from receiving acceptable pain and symptom management during their illness. Lack of knowledge about the use of analgesics, coupled with the lack of sophistication in diagnosing and treating the psychological complications of cancer, are examples of such educational barriers. Existing continuing care programs, like hospice, that manage symptoms in patients with far-advanced disease are currently insufficient to meet the needs of this large population. We need to address the access to expert care of distressing symptoms including pain and psychological distress as well as the quality of life of this patient population before we can fully address the options for terminating life. PMID- 1856504 TI - Euthanasia: the way we do it, the way they do it. AB - Although the Netherlands, Germany, and the United States are alike in having aging populations who die primarily of deteriorative diseases, they face end-of life dilemmas quite differently. In the United States, withholding and withdrawing of treatment are the only legally recognized means for easing dying. In Holland, voluntary active euthanasia is also practiced; in (West) Germany, assisted suicide is a legal option, usually outside the medical setting. This paper examines objections to these three practices, and observes the differences in the background cultures. Rather than reliance on any of the three, it argues that physician-assisted suicide in terminal illness is the practice most compatible with the United States' special characteristics. PMID- 1856505 TI - The challenge for future debate on euthanasia. AB - There is a significant pattern emerging in the discourse about euthanasia and assisted suicide as exemplified in the other articles in this special issue of the Journal of Pain and Symptom Management. That pattern is a dynamic tension that should be nurtured in the best interests of our options at the end of life. On the one hand, there is general acceptance of the right to self-determination and (within debatable limits) of the rationality and mortality of suicide. And on the other hand, there has been emphasis on comfort care through appropriately chosen medications and through a wholesome doctor-patient relationship that fosters a view of life worth living. Thus the creative tension is between the freedom to be dispatched with a minimum of suffering and the efforts to make it more desirable to stay and fight. It is a variation of the "fight or flight" response. The tension must be maintained for the good of us all. Too much emphasis on either one would skew the balance, and a dangerous extreme could result. PMID- 1856506 TI - Active euthanasia and forgoing life-sustaining treatment: can we hold the line? AB - Public sentiment in favor of permitting voluntary active euthanasia creates a dilemma for a bioethics rooted in a libertarian notion of autonomy. At stake in the active euthanasia debate is actually a question of power--the individual's assertion of sovereignty over the timing and circumstances of his or her own death. Also at stake is society's unwillingness to impose a conception of the good--and a good dying--on individuals whose personal values and conceptions of the good may differ. In order both to reject voluntary active euthanasia and to affirm the patient's right to forgo life-sustaining treatment, some societal conception of the good must be developed and agreed upon to counter unbridled claims of individual self-sovereignty over dying. Pragmatic arguments alone, such as the need to maintain confidence in the doctor-patient relationship, will not be sufficient. PMID- 1856507 TI - Assisted suicide: an evaluation. AB - Physician-assisted suicide is a form of euthanasia. As such, it is contrary to one's ethical responsibility to self, community, and God. Religious tradition, medical tradition, and modern psychology attest that physician-assisted suicide does not solve any human problem. PMID- 1856508 TI - Physician-assisted suicide: a double dilemma. AB - The ethical dilemma posed by the conflicts around physician-assisted suicide require at least three criteria that must be passed as a prerequisite for contemplating assisting someone toward death. 1) The request to die must not stem from a treatable depression. 2) The request must not stem from treatable discomfort, symptoms, and pain. 3) The exploration of the request to die must take place within the context of a relationship between physician and patient of some duration, depth, and intimacy. The moral dilemma posed by such a request also taps into the value system of the physician, which requires exploration and definition. Only then can the request be treated with the seriousness it deserves. PMID- 1856509 TI - Ethical decision-making in the care of the dying and its applications to clinical practice. AB - In caring for dying patients, physicians and health team members face a number of decisions about how best to proceed with treatment. Many of these decisions carry implications for the life of the patient, either directly or indirectly. Recent discussions about the morality and wisdom of euthanasia provide an excellent stimulus to reexamine the ethical nature of these decisions. This paper reviews five ethical principles, and describes a process of decision-making that can result in two broad paths of action in relation to life-prolonging treatment. Case examples are presented for illustration. Appropriate ethical practice can be differentiated from acting with the primary intent to take life (euthanasia). PMID- 1856510 TI - Killing the known dying: notes of a death watcher. PMID- 1856511 TI - Possible utility of serum determinations of CA 125 and CA 27.29 in breast cancer management. AB - The utility of measurement of serum levels of the tumor associated antigens CA 125 and CA 27.29 in detecting the presence of disease and in monitoring changes in disease status was examined in 63 patients with breast cancer. In patients with clinically detectable disease the CA 125 level was elevated in 59%, the CA 27.29 level in 59.5% and one or both markers in 84.6%. Specificity for presence of disease was 83.6% for CA 125, 88% for CA 27.29, and 69.1% for the two markers combined. Changes in marker levels of more than 50% correlated with clinical changes in disease status in 58% of cases for either CA 125 or CA 27.29 alone. In 87.5% of cases with clinically progressive disease one or both marker levels increased by more than 50% from the previous levels. In no case with greater than 50% increase in a marker level was there regression of disease. Thus, the use of these markers in combination might have utility in cases where diagnosis of recurrent disease is difficult or where monitoring of response to treatment is hampered by lack of measurable disease. PMID- 1856512 TI - Preliminary study on serum levels of mucinous like cancer antigen (MCA) in patients with breast disease: comparison with CEA. AB - MCA (mucinous-like cancer antigen) can be measured in the biological fluids of patients by means of a solid phase enzyme immunoassay. This study describes the results of MCA determination in sera of 230 patients with benign (99) and malignant (131) breast diseases. MCA levels were significantly higher in breast cancer patients than in non cancer patients and in healthy subjects (p less than 0.001). MCA concentrations tended to increase as the stage of the disease advanced. The 95th percentile of MCA value distribution in normal subjects showed a diagnostic sensitivity in breast cancer patients of 16.3% at stage I, 26.2% at stages II-III and 52% at stage IV. In a group of 118 cancer patients, MCA and CEA were tested simultaneously. The diagnostic sensitivity and specificity of MCA and CEA assays was very similar; nevertheless the association of the two tests showed 11 cases with high levels of MCA and low levels of CEA and 9 patients with high levels of CEA and low levels of MCA. Seventy-four out of 118 patients were negative for both markers and in 22 out of 118 patients markers were positive. The new marker MCA appeared to correlate with breast cancer and gave different information complementary to CEA. PMID- 1856513 TI - Impact of preoperative CA 15-3 levels in operable breast cancer. Comparison with tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA). AB - CA 15-3, TPA and CEA were assayed before surgery in 60 patients with breast cancer. A significant association was found between preoperative CA 15-3 levels and some of the most important prognostic factors in breast cancer, such as lymph node status and tumor size. No similar association was discovered for CEA and TPA. Preoperative CA 15-3 levels were also significantly associated with early recurrences of the disease, thus adding useful information to prognosis especially in N+ patients. PMID- 1856514 TI - The clinical status of immunoscintigraphy with monoclonal antibodies in ocular melanoma. AB - A summary is given of data on the clinical experience with the anti-melanoma antibody 225.28S in ophthalmology and the tissue expression of the high molecular weight-melanoma associated antigen in choroidal melanoma. Results are discussed in relation to other detection methods for ocular melanoma currently employed by the ophthalmologist. PMID- 1856515 TI - Evidence of a correlation between CA15.3 and estradiol serum levels in women with fibrocystic (non macrocystic) mastopathy. PMID- 1856516 TI - Seric SLX values in patients with lung tumors. PMID- 1856517 TI - Seric BCM-RIA levels in patients with lung pathologies. PMID- 1856518 TI - Clinical value of a mucin-like carcinoma-associated antigen (MCA) in patients with carcinomas of the kidney and the urinary collecting system. AB - A new tumor marker, mucin-like carcinoma-associated antigen (MCA), was evaluated in thirty-four patients with renal cell carcinomas and forty patients with carcinomas of the urinary collecting system. In the first group, specificity was 95%, sensitivity 65%, the predictive value for positive diagnosis was 94%, and for negative diagnosis 72%. In the second group specificity was 83%, sensitivity 71%, predictive value for positive diagnosis was 63%, and for negative diagnosis 88%. Receiver operating characteristic curves indicated that the maximum amount of information was greater in patients of the first group than the second (0.379 vs. 0.332 bits). In the light of these data, the MCA test can be recommended for assessing metastatic spread in patients particularly with renal cell carcinomas. PMID- 1856519 TI - [Correlation of placental villous immaturity and dysmaturity with clinical control of maternal diabetes]. AB - Strict clinical management of a diabetic mother who is pregnant reduces the risk of neonatal complications. It also reduces the frequency of fetal macrosomia. Diabetic mothers have a heavier placenta than mothers who are not diabetic. Light microscopic placental changes associated with diabetes include villous immaturity and dysmaturity. We have examined the placentas of 27 diabetic mothers whose maternal hemoglobin A1c (HbA1C) levels were measured throughout pregnancy. None of these placentas had a trimmed weight in excess of 600 grams. Eighteen of 27 specimens had immature villi. Four had dysmature villi. Three placentas had fibromuscular sclerosis within the villi. Five had cholangiosis and there was one cholangioma. Villous immaturity was present in 16 of 18 mothers whose HbA1C was more than 5.6% of the total hemoglobin. We found villous immaturity in 2 of 5, within 5.1-5.5% HbA1C. There was no villous immaturity in four cases whose HbA1C was less than 5.0% total hemoglobin. Our findings indicate that maternal hyperglycemia during pregnancy is associated with placental immaturity and dysmaturity. PMID- 1856520 TI - [Reevaluation of the diagnosis of placenta previa in midtrimester by means of transabdominal, transrectal and transvaginal ultrasonography]. AB - The incidence of placenta previa in mid-pregnancy diagnosed by ultrasonography is abnormally high in comparison with its incidence during labor. The cause of this discrepancy has not been fully elucidated. Detection of the cervix is fundamental to the diagnosis of placenta previa. In the present study, the detection rates for three methods, abdominal, rectal and vaginal scanning were compared and the time course of mid-pregnancy placenta previa was traced. The cause of the above mentioned discrepancy was thus elucidated. 1. Rate of cervix detection 1) In the 12-23 gestational week period, the cervix was successfully identified in 52.0 62.5% of cases by abdominal scanning, and in 85.7-87.5% by transrectal scanning. 2) The uterine isthmus was not identified by transabdominal scanning. 2. Changes in ultrasonographic findings with the passage of time 1) Transrectal scanning PMID- 1856521 TI - [Effect of malignant ascitic fluids and OK-432 on the induction of LAK activity in peripheral blood mononuclear cells of gynecological cancer patients]. AB - Recently, successful treatment of peritonitis carcinomatosa by intraperitoneal administration of lymphokine-activated killer (LAK) cells followed by intraperitoneal recombinant interleukin 2 (rIL-2) has been reported by several authors, in spite of the well documented results of the immunosuppressive activity of malignant ascitic fluid. We investigated the effect of malignant ascitic fluid on in vitro induction of LAK cells obtained from patients' peripheral blood mononuclear cells. We also examined whether Streptococcal preparation OK-432, which has been instilled into the peritoneal cavity to treat malignant ascites, is able to synergize with rIL-2 to induce LAK activity, and the following results were obtained; 1. A little augmentation of LAK activity was observed at a lower concentration of malignant ascitic fluid, while the results were diversified at a concentration higher than 10%. In two cases out of six, a severe suppressive effect was observed at a concentration higher than 40%. At the higher concentration, fewer cells were recovered after a 5 day culture in all cases. 2. No augmentation of LAK activity following the combination of OK-432 with rIL-2 was observed. At a lower concentration of OK-432 (ranging from 0.01 0.04KE/ml), the number of cells increased in comparison with rIL-2 alone. These results suggest that the potential of adoptively transferred LAK cells followed by rIL-2 was not effectively suppressed by malignant ascitic fluid in vivo and that the administration of OK-432 followed by rIL-2 could induce a larger number of various killer cells than rIL-2 alone. PMID- 1856522 TI - [The study on the degradation of prostacyclin activity in tissue culture supernatant of human placental villi]. AB - To clarify the role of placental villi in maintaining microcirculation in the placenta, we investigated the action to protect the activity of prostacyclin in the tissue culture supernatant of human placental villi. 1. The platelet aggregation inhibiting activity of prostacyclin was decreased very rapidly in Ringer buffer. 2. The tissue culture supernatant of human placental villi has an action which protects the activity of prostacyclin. On the other hand, in the tissue culture supernatant of human placental decidua no such action is prominent. 3. Human chorionic gonadotropin (hCG) also has an action which protects the activity of prostacyclin. These results indicated that human placental villi play an important role in maintaining placental microcirculation by producing substances which have a protective on the activity of prostacyclin. PMID- 1856523 TI - [Re-evaluation of hysteroscopy in the diagnosis of uterine endometrial cancer]. AB - To evaluate the clinical value of hysteroscopy in the management of endometrial cancer, findings in 3,681 patients with endometrial cancer treated between 1985 and 1989 at 167 hospitals in Japan were analyzed. In 1,040 of these patients, hysteroscopy was performed before operation. Pre-operative staging by fractional curettage with or without hysteroscopy was compared with post-operative histological diagnoses. The accuracy rates of diagnosis at final stages I and II were 91.4% and 79.4%, respectively, with hysteroscopy. There figures were not significantly different from those of 91.4% and 77.7% without hysteroscopy. The accuracy rate for diagnosis at the final stage I was 98.0% with the hystero fiberscope and significantly higher than that with rigid hysteroscopy (86.0%). Tumor cells in the pelvic cavity were examined at the time of operation in 1,115 patients. Tumor cells were found in 8.5% of those in stage I, 18.8% of those in stage II, 64.7% of those in stage III and 75.0% of those in Stage IV by hysteroscopy. These values were not significantly different from those of 7.3%, 22.7%, 57.1% and 81.1%, respectively, observed without hysteroscopy. These findings indicate that hystero-fiberscopy might be valuable for the pre-operative diagnosis of endometrial cancer, but has no effect on cytological malignancy in the peritoneal cavity. PMID- 1856524 TI - Ultracytochemical study on the permeability of the human amniotic epithelium. AB - In order to elucidate and characterize the transport pathway of the substances in the amniotic fluid, the permeability of the term human amnion was studied ultracytochemically, with lanthanum or horse radish peroxidase (HRP) as a tracer. Pieces of the term human amnion were exposed to the solutions containing lanthanum or HRP, and processed for electronmicroscopy. Precipitates indicating lanthanum or HRP were observed in the lateral intercellular spaces of the amniotic epithelial cells through the entire depth of the spaces. Generally, pinocytosis of HPR was not observed. In rare cases, however, diffuse uptake of HRP was noticed in the cells of the electron-lucent cytoplasm. These facts indicated that the human amniotic epithelium is quite permeable and that this particular intercellular pathway is important in the mechanism of the transfer of substances between the mother and the fetus. PMID- 1856525 TI - Effects of maternal postural change from supine to left-lateral on tocolysis, maternal cardiac function and pulsatility index of uterine artery. AB - In order to prove the usefulness of the left-lateral position (l-lat.) in preventing the cardiovascular complications associated with ritodrine, twenty nine patients having preterm labor were employed as the subjects of this study. Before and during the administration of ritodrine, the cardiac function was recorded by impedance cardiography. (1) When ritodrine was administered in the supine position, SV and CO first increased but eventually tended to decrease. When the position was changed to the l-lat. after SV and CO had almost returned to the preadministration level, HR decreased and SV and CO increased in 70% (10/14) of the patients. However, in patients showing no change in HR in the supine position, the cardiac function did not change either. (2) The magnitude of the changes in cardiac function accompanying the postural change during ritodrine administration was compared with that observed before administration. The decrease in HR and the increase in SV due to the postural change to the l-lat. were larger during ritodrine administration than before administration. The l lat. position is recommended as a means for preventing the side effects accompanying ritodrine administration. This study also indicated the possibility that the inferior vena cava may be more strongly compressed in the supine position by the relaxed gravid uterus. PMID- 1856526 TI - Effect of left-lateral position on maternal hemodynamics during ritodrine treatment in comparison with supine position. AB - Pregnant women are generally recommended to rest in the left-lateral position (l lat.) to avoid caval compression. We studied the influence of postural change from the supine position (sup.) to the l-lat. on maternal hemodynamics and tocolysis. The cardiac output (CO) was measured by impedance cardiography, while the pulsatility index of the uterine artery (PIUtA) was determined by the pulsed Doppler method. When the maternal posture was changed from sup. to l-lat, the following results were obtained. (1) The frequency of uterine contractions (UC) (preterm labor = 92) was significantly reduced (p less than 0.01). (2) The resting uterine tonus (n = 5) was also significantly decreased (p less than 0.05). (3) In the cases showing a decrease in the frequency of UC, the CO value was significantly increased (p less than 0.01), whereas PIUtA was significantly decreased (p less than 0.01). It is concluded that the postural change from sup. to l-lat. resulted in a decrease in the frequency of UC and the resting uterine tonus and at the same time an increase in the CO and decrease in the vascular resistance of the uterine artery. PMID- 1856527 TI - Calcium activated neutral protease and its endogenous inhibitor in human placental chorionic tissue. PMID- 1856528 TI - [A case of acute fatty liver of pregnancy]. PMID- 1856529 TI - [Giant placenta associated with transplacental hemorrhage]. PMID- 1856530 TI - [An operated case of gestational ovarian choriocarcinoma formed a huge abdominal tumor]. PMID- 1856531 TI - [Rupture of tubal pregnancy following vaginal total hysterectomy]. PMID- 1856532 TI - [Biomechanics of the Chiari pelvic osteotomy]. AB - We have reviewed our findings on 476 hip joints that underwent a Chiari pelvic osteotomy (Chiari) between June 1983 and March 1990, employing computer simulation using non-linear analysis based on the rigid-body spring model (RBSM) proposed by Kawai. We further made estimates of the changes in the hip abduction force resulting from the Chiari. The abduction force was measured by a Cybex II machine, before and after Chiari, and they were compared with those from simulation modeling (using the abduction muscle model: ABMM) for the power change expected by Chiari. According to the results in the RBSM, the resultant force, the abduction force, deviation of the pelvis, and the joint stress improved outcome after Chiari. Chiari had a positive effect on the peak torque of the hip abduction, though the abduction force was not fully restored clinically. The simulation by ABMM, showed similar results with the abduction force decreasing with increasing degree of hip abduction. From these results, we have developed and established a new technique for the reattachment of the greater trochanter in Chiari. PMID- 1856533 TI - Enhancement of new bone formation by hematoma at fracture site. AB - In order to study the osteogenetic potential of fracture hematoma, pellets which contain fluid components extracted from human fracture hematoma were transplanted to the subperiosteum of the rat parietal bone. Furthermore we have examined the effect of the fluid extract of the fracture hematoma and factors partially purified from this extract on DNA synthesis of cultured osteoblast-like cell line MC3T3E1. Implantation of the pellets containing the fluid extract did not promote new bone formation regardless of the presence of periosteum. This extract, in contrast, enhanced DNA synthesis of osteoblast-like cell line MC3T3E1 in a concentration dependent fashion. When this fluid extract was partially purified by ion exchange chromatography, the highest peak in DNA synthesis of MC3T3E1 was attained at 38mM NaCl, and the second highest peak at 290mM. These results suggest that the soluble extract from fracture hematoma contains growth factors which promote osteoblast proliferation, but does not possess osteogenetic potential. PMID- 1856534 TI - [Blood flow evaluations on normal spinal cord of rabbit and the effect of aortic ligation by radioactive microsphere technique]. AB - The microsphere technique was used to determine precise distribution of the spinal cord blood flow (SCBF) in rabbit and measurement of the SCBF was also carried out after the ligation of the thoracic aorta to examine the mechanism of collateral circulation. The results showed higher values of the SCBF in the cervical (42.3 +/- 17.1ml/100g/min) and lumbar spinal cord (42.2 +/- 25.5ml/100g/min), compared with the thoracic cord (36.6 +/- 15.5ml/100g/min). The segmental analysis of SCBF distribution revealed relatively higher in the lower cervical, lower thoracic and lumbar segments but showed lower values in the upper thoracic segments. The SCBF was also detectable only in 2-4 thoracic segments below the ligation level of the thoracic aorta, which suggests that sufficient pathway of collateral circulation is not plausible in the thoracic cord of rabbit. PMID- 1856535 TI - [Innervation of skeletal muscle by the lumbar sympathetic nervous system]. AB - The innervation of skeletal muscle by the lumbar sympathetic nerve was studied through the glyoxic acid histochemical method and the horseradish peroxidase method on 16 anesthesized rabbits. Blood flow changes in the quadriceps muscles during and after stimulation of the sympathetic nerves were evaluated by the heated thermocouple technique in 12 anesthesized rabbits. It seems likely that the postganglionic nerve fibers join to the spinal nerve at the intervertebral foramen and run into the peripheral nerves. The vastus medialis and rectus femoris were mainly innervated by the sympathetic neurons at different segmental levels. Sympathetic disturbance at the segmental level may occur when the spinal nerve is disturbed at the intervertebral foramen. Muscle blood flow decreased after sympathetic nerve stimulation for 1 minute. However, an increase took place after stimulation for 5 minutes. These results suggest the presence of some neurotransmitter present in the postganglionic nerve terminals. PMID- 1856536 TI - [MR imaging and disorders in orthopedics]. PMID- 1856537 TI - [Biomechanical principles and clinical experience of external fixation]. PMID- 1856538 TI - [Arthroplasty for osteoarthritis of the hip]. PMID- 1856539 TI - [Etiological factors and treatment of the senile femoral neck fracture]. PMID- 1856540 TI - [Endocrinologic approach to obesity and thinness ]. PMID- 1856541 TI - [Endocrinological approach to symptom and diagnosis of hyperglycemia ]. PMID- 1856542 TI - [Endocrinological approach to symptom and diagnosis of hypertension]. PMID- 1856543 TI - [Endocrinological approach to symptoms and diagnosis of goiter]. PMID- 1856544 TI - [Progress in diagnostic techniques for high-sensitivity hormone analysis and DNA diagnosis]. PMID- 1856545 TI - [Progress on diagnostic techniques of MRI for endocrine diseases]. PMID- 1856546 TI - [Progress, theory and practice of glucocorticoid therapy]. PMID- 1856547 TI - [Progress in insulin therapy of NIDDM]. PMID- 1856548 TI - [Progress in endocrinological therapy of abnormal calcium metabolism and metabolic bone diseases]. PMID- 1856549 TI - [Drug therapy of pituitary tumors]. PMID- 1856550 TI - [Endocrine hypertension]. PMID- 1856552 TI - [Diagnosis and therapy of thyroid diseases]. PMID- 1856551 TI - [Pitfall in diagnosis and therapy of diabetes mellitus]. PMID- 1856553 TI - [Mechanism of the development and management of a chronic state of allergic diseases--bronchial asthma]. PMID- 1856554 TI - [Systemic lupus erythematosus]. PMID- 1856556 TI - [Peptic ulcers]. PMID- 1856555 TI - [Diagnosis and therapy of chronic rheumatoid arthritis]. PMID- 1856557 TI - [Cerebrovascular disorders--current topics and therapeutic guidelines]. PMID- 1856558 TI - [Degenerative nervous system diseases]. PMID- 1856560 TI - [Diagnosis and therapy of coronary diseases]. PMID- 1856559 TI - [Metabolic nervous system diseases]. PMID- 1856561 TI - [Heart failure]. PMID- 1856562 TI - [Drug therapy of ventricular arrhythmia]. PMID- 1856563 TI - [Drug therapy of hypertension]. PMID- 1856564 TI - [Pulmonary fibrosis]. PMID- 1856565 TI - [Intractable airway infections and its management]. PMID- 1856566 TI - [Chronic respiratory failure]. PMID- 1856567 TI - [Anemia]. PMID- 1856568 TI - [Leukemia and malignant tumors]. PMID- 1856569 TI - [Hemorrhagic diathesis]. PMID- 1856570 TI - [Virus diseases]. PMID- 1856571 TI - [New antibacterial agents]. PMID- 1856572 TI - [Glomerulonephritis and nephrotic syndrome]. PMID- 1856573 TI - [Diagnosis and therapy of acute kidney failure]. PMID- 1856574 TI - Compositional changes in lipoproteins of subjects with non-insulin-dependent diabetes mellitus. PMID- 1856575 TI - Lipoprotein composition and HDL particle size distribution in women with non insulin-dependent diabetes mellitus and the effects of probucol treatment. AB - To further characterize the spectrum of potentially atherogenic disturbances in lipoprotein composition in non-insulin-dependent diabetes mellitus (NIDDM), we have studied a subset of women with NIDDM before and after treatment with the lipophilic lipid-lowering drug probucol (1 gm day), which we have shown corrects certain compositional abnormalities these women share with subjects who have hypercholesterolemia. Before treatment, the NIDDM group had a somewhat higher plasma triglyceride level (154 +/- 58.3 mg/dl, vs control, 80.0 +/- 21 mg/dl [mean +/- SD]; p less than 0.025) than controls but their cholesterol and high density lipoprotein cholesterol (HDL-C) levels did not differ from control levels. A number of significant disturbances, however, were present in the surface and core lipid composition of their lipoproteins. Although the cholesterol content of NIDDM low-density lipoprotein (LDL) was similar to that of controls, its content of sphingomyelin and phosphatidylinositol plus phosphatidylserine and sphingomyelin-to-lecithin ratio all were significantly reduced. Moreover, their very-low-density lipoprotein (VLDL) and HDL2 tended to have reduced amounts of free (unesterified) cholesterol (FC) relative to lecithin, and their HDL2 and HDL3 tended to be triglyceride enriched. Probucol therapy resulted in significant decreases in total plasma cholesterol (-15%), FC (-28%), HDL-C (-22%), and triglyceride (-16%) and in apoproteins A-I, B, and E (apo A-I, B, and E), without changing diabetic control (before probucol: hemoglobin A1, cholesterol, 10.7% +/- 2.7%; after probucol: 10.9% +/- 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856576 TI - Glomerular hemodynamic effects of dietary polyunsaturated fatty acid supplementation. AB - Dietary supplementation with polyunsaturated fatty acids (PUFAs) has been shown to alter the course of experimental renal disease. Although hemodynamic factors such as glomerular hypertension are felt to be important in the progression of renal disease, the effects of dietary PUFA supplementation on glomerular hemodynamics are unknown. The present investigation, therefore, was designed to evaluate the glomerular hemodynamic effects of dietary PUFA supplementation in normal rats. Male Sprague-Dawley rats were fed standard chow supplemented with either 20% (wt/wt) fish oil (FO) as a source of omega-3 PUFAs, 20% sunflower oil (SO) as a source of omega-6 PUFAs, or 20% coconut oil (CO) as a control diet. Micropuncture studies were performed after 4 to 6 weeks of dietary supplementation. Compared with CO rats, SO rats did not demonstrate any changes in glomerular hemodynamics. However, rats supplemented with FO demonstrated significant (p less than 0.05) increases in both single nephron glomerular filtration rate and single nephron plasma flow. These hemodynamic changes were not associated with alterations in glomerular capillary hydraulic pressure or the glomerular ultrafiltration coefficient. The increase in SNPF was primarily the consequence of a 37% reduction (p less than 0.05) in efferent arteriolar resistance. Thus dietary FO supplementation resulted in glomerular hyperfiltration and hyperperfusion. These hemodynamic actions may have important consequences in determining the effect of omega-3 PUFAs on the course of experimental and clinical renal disease. PMID- 1856577 TI - Regulation of glycolysis in the erythrocyte: role of the lactate/pyruvate and NAD/NADH ratios. AB - Mature erythrocytes, when removed from the circulation, exhibit severe disturbances of glycolytic flow, with accumulation not only of lactate, the ultimate product of glycolysis, but also of several upstream metabolic intermediates, primarily fructose-1,6-diphosphate, glyceraldehyde-3-phosphate, and dihydroxyacetone phosphate. This accumulation may be prevented (and also reverted) by allowing the diffusible end products lactate and pyruvate to leave the cell by equilibrating with a much larger extracellular compartment. The disturbance of erythrocyte glycolysis does not result from direct inhibition by lactate itself but from the interplay between the lactate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase (3-PGAD) reactions. The accumulation of intermediates reflects the increased lactate-to-pyruvate ratio; this leads to a secondary imbalance of the nicotinamide adenine dinucleotide-to-reduced nicotinamide adenine dinucleotide (NAD-to-NADH) ratio, which in turn slows down glycolysis at the 3-PGAD step, whose upstream metabolites then pile up. No accumulation, however, takes place if the lactate-to-pyruvate ratio is maintained constant in the extracellular compartment, regardless of concentrations. These studies demonstrate that orderly glycolysis in the erythrocyte is regulated by the NAD-to-NADH ratio and also provide a method that makes possible the in vitro study of erythrocyte glycolysis. PMID- 1856578 TI - Clearance and synthesis rates of beta 2-microglobulin in patients undergoing hemodialysis and in normal subjects. AB - Retention of beta 2-microglobulin in patients undergoing hemodialysis is associated with a beta 2-microglobulin-derived amyloidosis. Removal of beta 2 microglobulin by renal replacement therapy has been proposed for the prevention of this amyloidosis. Currently, however, data on the beta 2-microglobulin synthesis rate in patients undergoing hemodialysis are scarce, and consequently it remains speculative how much removal would be necessary to counterbalance synthesis. The plasma kinetics of iodine 131-labeled beta 2-microglobulin were therefore examined in 11 patients with anuria who were undergoing long-term hemodialysis. Five healthy persons served as controls. Kinetic modeling of the plasma curves showed that the data fitted a two-pool model (r2 greater than 0.96) consisting of a rapid 2 to 4 hour distribution phase followed by a less steep curve, described by the plasma (metabolic) clearance (Clp). Synthetic rates were calculated from Clp and the beta 2-microglobulin steady state plasma concentration (plus beta 2-microglobulin removal during hemodialysis in the case of high flux hemodialysis). The results showed a significantly higher Clp in normal controls as compared with patients undergoing hemodialysis (65.5 +/- 12.8 ml/min (mean +/- SD) versus 3.4 +/- 0.7 ml/min). In contrast, the beta 2 microglobulin synthesis rate in the patient group (3.10 +/- 0.79 mg/kg/day) was not significantly different from that of normal controls (2.40 +/- 0.67 mg/kg/day), which was due to markedly elevated beta 2-microglobulin plasma concentrations in the patients (37.6 +/- 14.1 mg/L vs 1.92 +/- 0.27 mg/L). These findings suggest that the presence of end-stage renal disease does not have a significant impact on the beta 2-microglobulin generation rate. The degree of accumulation of beta 2-microglobulin in patients undergoing hemodialysis seems to depend on the loss of renal excretory function. PMID- 1856579 TI - Enhanced GFR response to oral versus intravenous arginine administration in normal adults. AB - Both oral protein ingestion and intravenous amino acid infusions have been shown to increase glomerular filtration rate (GFR) and renal plasma flow (RPF) in normal subjects. Although the mechanism of this effect is not known, the renal responses to these loads have been associated with increases in peripheral glucagon concentrations. Conflicting data exist concerning the role of glucagon in the hyperfiltration response after an oral protein meal or administration of an intravenous amino acid mixture. Using a single amino acid as the stimulus for hyperfiltration, we compared the renal responses in six normal subjects to 30 gm oral arginine-HCl, intravenous arginine-HCl, and intravenous glucagon infused at the rate of 10 ng/kg/min. GFR, RPF, and glucagon concentration, as well as levels of plasma amino acids and selected gastrointestinal hormones, were measured for six 30-minute clearance periods after each load. Significant rises in mean peak GFR were noted after both oral arginine (104 +/- 5 ml/min x 1.73 m2 to 145 +/- 9 ml/min x 1.73 m2, p less than 0.02) and intravenous arginine (118 +/- 10 ml/min x 1.73 m2 to 134 +/- 11 ml/min x 1.73 m2, p = 0.02) administration. Mean peak RPF rose significantly after oral arginine (510 +/- 26 ml/min x 1.73 m2 to 710 +/- 32 ml/min x 1.73 m2, p less than 0.01) but not after intravenous arginine (616 +/- 60 ml/min x 1.73 m2 to 687 +/- 64 ml/min x 1.73 m2, p = 0.18). Intravenous glucagon infusion also increased both mean peak GFR (99 +/- 9 ml/min x 1.73 m2 to 149 +/- 10 ml/min x 1.73 m2, p less than 0.01) and RPF (514 +/- 48 ml/min x 1.73 m2 to 771 +/- 38 ml/min x 1.73 m2, p less than 0.01) significantly. We found the mean peak percent rise in GFR (43% +/- 13%) and RPF (42% +/- 12%) after oral arginine to be notably greater than that after intravenous arginine (14% +/- 5% and 13% +/- 9%, respectively). However, the mean peak percent rise in glucagon concentration after oral arginine was significantly lower than that after intravenous arginine (62% +/- 25% versus 479% +/- 176%, respectively, p = 0.04). Infusion of glucagon increased GFR (54% +/- 13%) and RPF (55% +/- 12%) to a degree similar to that seen after oral arginine, but again with a significantly higher mean peak percent rise in peripheral glucagon concentrations when compared with the rise after oral arginine (798% +/- 348% vs 62% +/- 25%, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1856580 TI - Carotenoids and liposoluble vitamins in liver cirrhosis. AB - The role played by carotenoids, retinol and tocopherol in quencing oxidative cellular damage and combatting tumor growth is well documented, but little is known about their activity in human liver cirrhosis (LC), where oxidative damage and tumoral complications are common-place. We investigated 59 patients with LC of different etiology on admission to hospital and compared them with 32 healthy controls, matched for age and sex. Nutritional (cutaneous skinfolds, creatinine height index) and serum parameters were determined; of these, alpha- and beta carotene, cryptoxanthin, lycopene, retinol and alpha-tocopherol were detected by an high-performance liquid chromatographic (HPLC) technique, devised in our laboratory, which afforded an accurate and simultaneous resolution of all six compounds. The results point to a significant reduction in almost all the vitamin factors in LC, as well as in total serum lipids. In consequence, the ratio tocopherol/total serum lipids remains almost unchanged: 2.45 +/- 0.08 (m +/- se) in controls and 2.34 +/- 0.16 in patients. The effects of age, sex, nutritional habits, alcohol, malnutrition and the severity of the disease were also evaluated in relation to the vitamin-factor levels. It is suggested that the reduced levels observed in LC patients are due to a number of factors including portal hypertension and lymphatic circulation impairment, and it is concluded that thorough screening and improved diet are beneficial in the follow-up of LC. PMID- 1856581 TI - Detection of endotoxin in triglyceride-rich lipoproteins in vitro. AB - Numerous investigations have been performed in which volunteers have received infusions of triglyceride-rich lipoproteins without apparent screening of the infusates for bacterial endotoxin. This study was designed to examine the capacity of triglyceride-rich lipoproteins to mask their endotoxin content in vitro as measured by a chromogenic modification of the standard Limulus assay. Lipoproteins and lipoprotein-deficient plasma were isolated from normal human plasma by sequential ultracentrifugation under apyrogenic conditions. Individual lipoproteins and a synthetic lipid emulsion were suspended in 10% lipoprotein deficient plasma. Samples were then incubated at 37 degrees C for 4 hours with increasing concentrations of E. coli (055:B5) endotoxin and assayed for detectable endotoxin activity. The capacity to inhibit detection of endotoxin in 10% lipoprotein-deficient plasma was significantly increased (10 to 100 times) by the addition of VLDL (1.0 mg triglyceride/ml), chylomicrons (1.0 mg triglyceride/ml), or the synthetic lipid emulsion (2.5 mg triglycerides/ml). These data demonstrate that triglyceride-rich lipoproteins, and the synthetic lipid emulsion, can markedly inhibit the detection of endotoxin by the Limulus assay in vitro. In addition to the potential of harm to experimental subjects, infusion of endotoxin could vitiate kinetic studies by direct alteration of lipoprotein metabolism and by inducing changes in hepatic blood flow. Thus experimental protocols that involve the infusion of humans with triglyceride-rich lipoproteins should include detailed testing for the presence of endotoxin. PMID- 1856583 TI - Egas Moniz: neurologist, statesman, and Nobel laureate. PMID- 1856582 TI - Enzyme-linked immunosorbent assay of transthyretin devised for semimicro plasma diagnosis of familial amyloidotic polyneuropathy. AB - A highly sensitive and reproducible enzyme-linked immunosorbent assay for human transthyretin was developed. The method is most suitable to serial monitoring of transthyretin peaks in reverse-phase high-performance liquid chromatography for the diagnosis of familial amyloidotic polyneuropathy based on isolation of variant transthyretin. This method semimicronized the original diagnostic method, requiring plasma samples of only 0.2 ml. The present enzyme-linked immunosorbent assay method is also applicable to determine transthyretin in plasma and cerebrospinal fluid. It correlated well when compared with a commercially available single radial immunodiffusion (r = 0.951, p less than 0.001). PMID- 1856585 TI - The respiratory complications of leptospirosis. AB - Leptospirosis is an uncommon disease. Respiratory failure attributable to this infection is unusual, but remains a major cause of mortality. Mechanical ventilation has been required for patients with significant alveolar hemorrhage and the adult respiratory distress syndrome. We report a patient with ventilatory failure due to the severe muscle weakness associated with leptospirosis and review the pulmonary consequences of this infection. PMID- 1856584 TI - The epidemiology of Lyme disease in Kentucky, 1985-1990. AB - Lyme Disease has become the most common vector-borne disease in the United States. To assess the extent of the disease in Kentucky, all case reports were reviewed for 1985-1990. A total of 51 cases met the current case definition. Epidemiologic features were similar to those reported nationally. Although the recognized tick vectors for Lyme Disease have still not been identified in Kentucky, physicians should educate their patients on the risk of Lyme Disease and measures to prevent tick bites. Reporting cases of Lyme Disease will continue to be important so that trends in the disease's occurrence in Kentucky can be monitored. PMID- 1856586 TI - A unique inlet [the ascending aorta] for extra-anatomic bypass of infected arterial prostheses. AB - Infection is the most dreaded complication associated with implantation of a prosthetic arterial graft. The reported incidence of primary graft infection varies from 1.3% to 6.0%, with a mortality rate from this complication as high as 75%. Although remote bypass followed by complete removal of the infected prosthesis has proven to be a satisfactory method of treatment, in certain instances remote bypass alone is not feasible and other modes of surgical treatment must be employed. Such conservative methods of management of infected aorto-iliac-femoral prosthesis sometimes irradicate infection. The only certain cure, however, is obtained by totally removing the graft. And the success of extra-anatomic axillofemoral techniques has led to its extended use. The addition of a cross-limb on an axillo-unilateral femoral graft to form an axillobilateral femoral graft was described by Sauvage and Wood, reasoning that the higher flow rate in the axillary limb of the axillobilateral femoral graft would result in an improved patency rate compared with that of axillounilateral femoral grafts. Additionally, both medial (obturator foramen) and lateral extra-anatomic remote bypass of infected femoral prosthesis have been used, successfully. The current case illustrates the complexity of management, once sepsis occurs. It further focuses on groin, retroperitoneal and bilateral axillo-femoral tract infection with prolonged (apparently innocuous) graft exposure and finally points out the utility of the ascending aorta as an alternative extra-anatomic inlet to perfuse the lower extremities. PMID- 1856587 TI - Thallium redistribution does not predict perioperative cardiac complications following vascular surgery. AB - Utility of preoperative stress thallium scintigraphy (STS) was determined in 59 patients, thought to be at increased risk, prior to major vascular surgery from July 1987 to February 1990. Forty-seven had oral dipyridamole and 12 underwent exercise STS. Thallium redistribution (TR) was present in 61% (n = 36); fixed defects were present in 59% (n = 35); and some combination of defects was present in 76% (n = 45). Perioperative cardiac complications (CC = congestive heart failure [n = 3], ventricular arrhythmia [n = 2], and MI [n = 1]) were present in 8.5% (6 CC in 5 patients). Incidence of CC was 8.3% (3/36) in those with TR, and 8.7% (2/23) without TR (relative risk = 0.95). Perioperative MI was present in 2.8% (1/36) with TR vs. 0% (0/23) without. Though mortality was 3.4%, no perioperative deaths were from cardiac disease. Utility of STS is not clearly established for prediction of perioperative cardiac risk after major vascular surgery. PMID- 1856588 TI - Where nobody knows your name. PMID- 1856589 TI - Regulation of mail-order pharmacy. PMID- 1856590 TI - Medical and legal aspects of rape and resistance. PMID- 1856591 TI - Fetal protection policies. Effective tools for gender discrimination. PMID- 1856592 TI - Lipopolysaccharide-dependent and lipopolysaccharide-independent pathways of monocyte desensitisation to lipopolysaccharides. AB - The present study demonstrates that with time in culture blood monocytes (MO) lose their ability to express procoagulant activity (PCA) and secrete tumor necrosis factor-alpha (TNF alpha) in culture medium in response to lipopolysaccharide (LPS) stimulation. Thus, upon 10 micrograms/ml LPS stimulation for 4 hours 2-day-old MO produced lower levels of PCA and TNF alpha than fresh MO. The decrease in responsiveness was not caused by cell death, since in the case of TNF alpha it was fully reversible by interferon-gamma (IFN-gamma). Compared with cells pre-incubated in medium alone, the responsiveness of MO pre incubated in LPS was further decreased. Thus, in MO LPS pre-incubation was followed by an LPS refractory state. It was expected that the decrease in responsiveness induced by cultivation in medium alone was mediated by LPS contamination of culture medium. However, as we were unable to prevent this decrease by neutralizing LPS contamination of the culture medium with polymyxin B, the loss in LPS-induced activities of cultured MO is likely to be mediated by culture conditions other than LPS contamination. Taken together the present data demonstrate that LPS-dependent as well as LPS-independent pathways of MO desensitization to LPS exist. PMID- 1856593 TI - Phagocytosis of opsonized yeast induces tumor necrosis factor-alpha mRNA accumulation and protein release by human polymorphonuclear leukocytes. AB - In this report we show that phagocytosis of yeast particles opsonized with IgG (Y IgG) by human polymorphonuclear cells (PMN) results in the selective induction of tumor necrosis factor (TNF-alpha) messenger RNA (mRNA) and release of its mature protein. Lipopolysaccharide (LPS) was also found able to induce TNF-alpha secretion by PMN, but was a less potent stimulus compared with Y-IgG. There was no evidence of interleukin-6 (IL-6) gene expression in PMN after phagocytosis of Y-IgG or in response to LPS, whereas IL-6 mRNA expression and secretion were induced by either stimulus in monocytes. These findings demonstrate that a physiological function such as phagocytosis modulates the gene expression for a cytokine in PMN and shed new light on the understanding of the pathogenesis of the inflammatory process. PMID- 1856594 TI - Kinetics of phagocytosis and phagosome-lysosome fusion in hamster lung and peritoneal macrophages. AB - The time course of phagocytosis and phagosome-lysosome fusion (PLF) in lung and peritoneal macrophages (LMs and PMs) was measured. Lysosomes in unelicited hamster LMs and PMs were labeled with lucifer yellow. Macrophages then phagocytized heat-killed Saccharomyces cerevisiae (yeast) and were evaluated at several time points for the degree to which yeast particles were adherent vs. internalized and for the presence or absence of PLF as based on the presence or absence of lucifer yellow in yeast-containing phagosomes. A three-compartment model (adherent, ingested, fused) of independent phagocytosis and PLF was developed; the number of yeast particles in each compartment was counted, and rate constants for ingestion and fusion were determined. Comparison of rate constants showed that ingestion was significantly faster in PMs (0.047 +/- 0.005 min-1) than in LMs (0.016 +/- 0.005 min-1) (mean +/- pooled SEM; P less than 0.001). Similarly, PLF was significantly faster in PMs (0.109 +/- 0.013 min-1) than in LMs (0.046 +/- 0.013 min-1) (P less than 0.003). PMID- 1856595 TI - Viscoelastic and motile properties of hamster lung and peritoneal macrophages. AB - The motile and rheologic properties of hamster lung and peritoneal macrophages (LMs and PMs) were examined by following the motions of magnetizable iron oxide (gamma-Fe2O3) particles contained within phagolysosomes of these cells. As a measure of intracellular motility, gamma-Fe2O3 particles in cells were magnetically aligned and the decay rate of the remanent magnetic field (RMF) in the direction of initial magnetization was monitored over time. Cytoplasmic rheology was measured by twisting the intracellular particles with a magnetic field (Btw) applied perpendicularly to the direction of initial magnetization. We measured changes in the RMF associated with application and removal of Btw. Intracellular motility in LMs and PMs was not significantly different (P greater than 0.20); similarly, cytoplasmic viscosity was not significantly different in LMs and PMs (P greater than 0.12); deformation on application of torque was significantly greater (P less than 0.0001) and elastic recoil on removal of torque was significantly smaller (P less than 0.0001) in PMs than in LMs; and by qualitative observation, the yield stress of cytoplasm (associated with a plastic, nonrecoverable deformation) was lower in PMs than in LMs. These results show that although cytoplasmic motion and viscosity are similar in the two cell types, PM cytoplasm is less stiff than LM cytoplasm as determined by yield stress. PMID- 1856596 TI - Determination of the number and distribution of macrophages, lymphocytes, and granulocytes in the mouse uterus from mating through implantation. AB - The concentration and distribution of F4-80 positive cells (macrophages) and common leukocyte antigen (CLA) positive (bone marrow derived) cells were assessed in mouse uterus between days 1 and 8 of pregnancy. High numbers of polymorphonuclear leukocytes and lymphocytes were present on days 1 and 2, but not thereafter. Granulocytes were found both in the endometrium and within the luminal epithelium. The percentage of total cells contributed by macrophages was high on days 1 and 2. That percentage decreased significantly on day 3, then increased again on day 5 and remained high through day 8. Macrophages always were found in myometrial stroma. Macrophages were found throughout the endometrium on days 2 through 8. High numbers of macrophages were observed near epithelia, particularly on days 1, 2, 4, and 5. Few F4-80+ or CLA+ cells were observed within the developing primary and secondary decidua. The results demonstrate that an inflammation-like cellular response occurs in the uterus following mating and that macrophages are a major cellular component of the uterus during early pregnancy. PMID- 1856597 TI - Genetic resistance/susceptibility to mycobacteria: phenotypic expression in bone marrow derived macrophage lines. AB - Congenic strains of mice susceptible (B10A.Bcgs) or resistant (B10A.Bcgr) to BCG were established. Here we describe the model system which has been established to analyze the functional activities of macrophages in the two strains. We have immortalized bone marrow macrophages from B10A.Bcgs and B10A.Bcgr congenic strains of mice and derived cloned macrophage lines designated B10S and B10R, respectively. B10R and B10S cell lines exhibited surface markers and morphology typical of macrophages. B10S and B10R were similar in their phagocytic activity, in their level of c-fms, in their transforming growth factor beta (TGF beta) mRNAs expression, and in their expression of tumoricidal activity in response to interferon-gamma (IFN gamma) plus lipopolysaccharides (LPS). However, B10R macrophages expressed a higher level of la mRNA when activated with IFN gamma compared with B10S macrophages. Analysis of the bacteriostatic activity of the two cell lines revealed that B10R macrophages were much more active in inhibiting Mycobacterium smegmatis replication than B10S. To measure the intracellular destruction of bacilli, a bactericidal assay based on hybridization with an oligonucleotide probe specific for mycobacterial ribosomal RNA was designed. The results demonstrated that B10R macrophages were endowed with enhanced constitutive bactericidal activity as compared with B10S. In conclusion we have obtained macrophage lines from bone marrow of B10A.Bcgs and B10A.Bcgr mice that express to a similar extent functional and phenotypic characteristics of macrophages. However, we demonstrate that relative to B10S macrophages, the B10R macrophages have higher expression of la mRNA and that they are constitutively more active in expressing mycobactericidal activity. PMID- 1856598 TI - [Ca2+]i changes and respiratory burst in human neutrophils and monocytes induced by NAP-1/interleukin-8, NAP-2, and gro/MGSA. AB - The stimulatory effects of neutrophil-activating peptide 1 (NAP-1), also termed interleukin 8 (IL-8), neutrophil-activating peptide 2 (NAP-2), and melanoma growth-stimulatory activity (gro/MGSA) on human neutrophils and monocytes were compared on the basis of two responses that can be assessed in real time, the changes in cytosolic free calcium and the respiratory burst. All three peptides induced a rapid and transient rise of cytosolic-free calcium and the respiratory burst in neutrophils. Both responses were also obtained in monocytes on stimulation with NAP-1/IL-8 and gro/MGSA, but not with NAP-2, which appeared to be more selective for neutrophils. Pretreatment with concanavalin A (ConA) enhanced several fold the rate and duration of the respiratory burst of neutrophils stimulated with all three peptides and of monocytes stimulated with NAP-1/IL-8 and gro/MGSA, but not with NAP-2. Sequential stimulation showed mutual cross desensitization by NAP-2 and gro/MGSA in neutrophils. In addition, desensitization of neutrophils toward NAP-2 and gro/MGSA, and of monocytes toward gro/MGSA, was obtained by prestimulation with NAP-1/IL-8. Prestimulation with either NAP-2 or gro/MGSA, however, did not desensitize the cells for NAP-1/IL-8. These results suggest that under conditions where multiple stimulatory agents are produced, neutrophil-activating peptides may contribute to the formation of substantial amounts of oxygen-derived radicals. In addition, the study shows that NAP-1/IL-8 and gro/MGSA, but not NAP-2, have some stimulatory effects on monocytes as well. PMID- 1856599 TI - Mononuclear cell adherence induces neutrophil chemotactic factor/interleukin-8 gene expression. AB - The accumulation of polymorphonuclear cells (PMN) in tissue is an essential element of the inflammatory response that is important in host defense. Adherence to endothelium constitutes the first step in PMN migration from the vascular compartment to the interstitium. We demonstrate that human peripheral blood mononuclear cells (PBMC) adherent to plastic can result in expression of interleukin-8 (IL-8), a potent PMN chemoattractant and activating cytokine. Northern blot analyses showed PBMC adherent to plastic expressed IL-8 steady state mRNA levels by 30 min, peaked at 8 h, and then decreased over the next 16 h. In contrast, nonadherent PBMC (cultured in teflon chambers) expressed less than 25% of the maximal IL-8 steady-state mRNA levels as compared with adherent PBMC. Adherent PBMC-associated IL-8 determined by immunochemistry, supernatant chemotactic bioactivity, and extracellular antigenic IL-8 paralleled IL-8 mRNA expression. Antigenic and bioactive IL-8 were significantly apparent by 4-8 h, respectively, and increased significantly to maximal levels by 24 h. Furthermore, adherent PBMC IL-8 gene expression was suppressed by either concomitant treatment with actinomycin-D or cycloheximide, yet specific neutralizing antibodies directed against either IL-1 beta or tumor necrosis factor (TNF)-alpha failed to alter adherence-induced steady-state IL-8 mRNA levels. These data support the hypothesis that PBMC adherence is an important signal for the production of IL-8, and may be essential to the development of the inflammatory response through the elicitation of PMN. PMID- 1856600 TI - Colony-stimulating factors increase resistance to atypical mycobacteria in resistant mice, whereas they decrease resistance in susceptible strains of mice. AB - Inbred strains of mice, notably the susceptible C57BL/6 and the resistant A/J strains of mice, were infected with a strain of Mycobacterium evium. The infection in the visceral organs of mice was then studied, and the effect of colony-stimulating factors, i.e., interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (CSF 1) on the infectious process was evaluated. Infusion of GM-CSF, CSF-1, and IL-3 led to a significant, albeit rather modest, increase in the mycobacterial resistance of A/J mice, as seen by a decrease in the number of colony-forming units (CFU) in the organs. Conversely, these CSFs dramatically increased the susceptibility of C57BL/6 mice, as seen by increased bacterial numbers in the spleens and livers. In vitro studies demonstrated that resident peritoneal macrophages from susceptible mice were more permissive than cells from resistant mice for mycobacterial growth. Application of CSFs on peritoneal macrophage monolayers led to an increased growth in both A/J and C57BL/6 monolayers for IL-3 and CSF-1 and a small microbiostatic effect for GM-CSF. Cytokine treatment did not, however, change the resistance/susceptibility phenotype of isolated macrophages. Our results indicate that CSFs may exert beneficial or detrimental effects on resistance to mycobacteria depending on the host genetic make up. PMID- 1856601 TI - Cryopreserved cytoplasts from human polymorphonuclear leukocytes (cytokineplasts) are chemotactic at speeds comparable to those of fresh intact cells. AB - Cytokineplasts (CKP) are granule-poor cytoplasts from human polymorphonuclear leukocytes (PMN) that retain motile function, even (unlike the parent PMN) after cryopreservation. Employing time-lapse videomicroscopy, we examined the chemotactic properties of CKP after cryopreservation toward erythrocytes lysed by laser microirradiation. Paths of locomotion were plotted for six CKP in the field, and velocities were calculated at 10-sec intervals. Mean velocities of the six fragments, ranging from 9.3 to 20.8 microns/min, are of the order of fresh, intact PMN, the fastest of locomoting cells. PMID- 1856602 TI - Clarification of the potential role of CSF-1 in activation of macrophages. PMID- 1856603 TI - Guided tissue regeneration for bony defects and dehisced titanium endosseous implants. PMID- 1856604 TI - Higher aliphatic 2,4-diketones: a ubiquitous lipid class with chelating properties, in search of a physiological function. AB - A group of homologous 2,4-diketones with chain lengths from C13 to C25, derived from fatty acids, is present in human and mammalian tissues and urine. The presence of this lipid class, members of which possess marked chelating properties, adequately accounts for the well-documented antiallergic activity of tissue and urine extracts on isolated smooth muscle preparations and in guinea pigs in vivo. This review summarizes the investigations leading to the discovery of this lipid class. It is postulated that the observed antiallergic activity of 2,4-diketones may be explained by the intracellular sequestration of calcium ions transiently liberated from intracellular storage pools after an agonist-receptor interaction, thus blocking response to the agonist. The true physiological function (or functions) of this lipid class has not been defined. The chelating properties of 2,4-diketones suggest their involvement in intracellular ionic interactions. PMID- 1856605 TI - Effects of atherogenic diet consumption on lipoproteins in mouse strains C57BL/6 and C3H. AB - Inbred mouse strains C57BL/6J (B6) (susceptible) and C3H/HeJ (C3H) (resistant) differ in atherosclerosis susceptibility due to a single gene, Ath-1. Plasma lipoproteins from female mice fed chow or an atherogenic diet displayed strain differences in lipoprotein particle sizes and apolipoprotein (apo) composition. High density lipoprotein (HDL) particle sizes were 9.5 +/- 0.1 nm for B6 and 10.2 +/- 0.1 nm for C3H. No major HDL particle size subclasses were observed. Plasma HDL level in the B6 strain was reduced by the atherogenic diet consumption while the HDL level in the resistant C3H mice was unaffected. The reduction in HDL in the B6 strain was associated with decreases in HDL apolipoproteins A-I(-34%) and A-II(-60%). The HDL apoC content in mice fed chow was two-fold higher in C3H than B6. Lipoproteins containing apolipoprotein B (VLDL, IDL, LDL) shifted from a preponderance of the B-100 (chow diet) to a preponderance of the B-48 (atherogenic diet). The LDL-particle size distribution was strain-specific with the chow diet but not genetically associated with the Ath-1 gene. In both strains on each diet, apolipoprotein E was largely distributed in the VLDL, LDL, and HDL fractions. The B6 strain became sixfold elevated in total lipoprotein E content which in the C3H strain was not significantly affected by diet. However, the C3H LDL apoE content was reduced. On both diets, the C3H strain exhibited apolipoprotein E levels comparable to the atherogenic diet-induced levels of the B6 mice. PMID- 1856606 TI - Use of determinations of 7-lathosterol (5 alpha-cholest-7-en-3 beta-ol) and other cholesterol precursors in serum in the study and treatment of disturbances of sterol metabolism, particularly cerebrotendinous xanthomatosis. AB - The sterol composition of sera from patients with cerebrotendinous xanthomatosis (CTX) was investigated by gas chromatographic analysis of saponified extracts, using a polar (CP Wax 52CB) and an apolar (CP Sil 5CB) capillary column. Apart from already known sterols, the presence of increased amounts of 8-lathosterol (5 alpha-cholest-8(9)-en-3 beta-ol) and significant amounts of 8-dehydrocholesterol (cholesta-5,8-dien-3 beta-ol) were noticed. The latter compound has not been detected previously in human serum and possibly represents a hitherto unknown cholesterol precursor. The apparently elevated levels of delta 8-sterols in CTX serum suggests partial inhibition of migration of the 8,9 double bond to the 7,8 position in this condition. The concentration of 7-lathosterol, an indicator of cholesterol production rate, is also highly elevated in CTX serum and quickly returns to normal values after oral bile acid therapy. Determinations of serum lathosterol are not only useful in the follow-up of therapy of CTX patients, but also in the follow-up of hypercholesterolemic patients treated with either HMG CoA reductase inhibitors or bile acid sequestrants. PMID- 1856607 TI - Calcium binding by monosulfate esters of taurochenodeoxycholate. AB - The effect of sulfate esterification of the 3 alpha- or 7 alpha-hydroxyl groups of taurochenodeoxycholate on calcium binding was studied at 0.154 M NaCl in the presence and absence of phosphatidylcholine using a calcium electrode. For comparison, similar studies were made with taurochenodeoxycholate, taurodeoxycholate, and taurocholate. No high affinity calcium binding was demonstrable for any of these bile salts in pre-micellar solutions. Taurine conjugated bile salts have greater affinity for calcium when in a micellar form. At elevated bile salt concentrations, the calcium binding of unsulfated dihydroxy taurine conjugates was similar to that of the monosulfate esters of taurochenodeoxycholate. The presence of phosphatidylcholine decreased calcium binding of the unsulfated dihydroxy bile salts and slightly increased calcium binding by taurocholate. However, the addition of phosphatidylcholine to monosulfate esters of taurochenodeoxycholate results in large increments in calcium binding. The results indicate that increased calcium binding due to the presence of phosphatidylcholine in bile salt solutions depends, in part, on the hydrophilicity of the bile salt and that the interaction of monosulfate esters of taurochenodeoxycholate with phosphatidylcholine leads to the formation of a high affinity calcium binding site. PMID- 1856608 TI - Inhibition of cholesterol absorption and synthesis in rats by sesamin. AB - The effects of sesamin, a lignan from sesame oil, on various aspects of cholesterol metabolism were examined in rats maintained on various dietary regimens. When given at a dietary level of 0.5% for 4 weeks, sesamin reduced the concentration of serum and liver cholesterol significantly irrespective of the presence or absence of cholesterol in the diet, except for one experiment in which the purified diet free of cholesterol was given. On feeding sesamin, there was a decrease in lymphatic absorption of cholesterol accompanying an increase in fecal excretion of neutral, but not acidic, steroids, particularly when the cholesterol-enriched diet was given. Sesamin inhibited micellar solubility of cholesterol, but not bile acids, whereas it neither bound taurocholate nor affected the absorption of fatty acids. Only a marginal proportion (ca. 0.15%) of sesamin administered intragastrically was recovered in the lymph. There was a significant reduction in the activity of liver microsomal 3-hydroxy-3 methylglutaryl coenzyme A reductase after feeding sesamin, although the activity of hepatic cholesterol 7 alpha-hydroxylase, drug metabolizing enzymes, and alcohol dehydrogenase remained uninfluenced. Although the weight and phospholipid concentration of the liver increased unequivocally on feeding sesamin, the histological examination by microscopy showed no abnormality, and the activity of serum GOT and GPT remained unchanged. Since sesamin lowered both serum and liver cholesterol levels by inhibiting absorption and synthesis of cholesterol simultaneously, it deserves further study as a possible hypocholesterolemic agent of natural origin. PMID- 1856610 TI - Potential bile acid metabolites. XVIII. Synthesis of stereoisomeric 3,6,12 alpha trihydroxy-5 beta-cholanoic acids. AB - Two new 6-hydroxylated bile acids, 3 beta, 6 alpha, 12 alpha- and 3 beta, 6 beta, 12 alpha-trihydroxy-5 beta-cholanoic acids, were synthesized from deoxycholic acid. In addition, their C-3 epimers, 3 alpha, 6 alpha, 12 alpha- and 3 alpha, 6 beta, 12 alpha-trihydroxy acids, were prepared by a new route. The principal reactions used were 1) 6 beta-hydroxylation of 3-methoxy-3,5-dienes with m chloroperbenzoic acid in aqueous dioxane; 2) catalytic hydrogenation of the resulting 6 beta-hydroxy-3-oxo-4-enes to the 6 beta-hydroxy-3-oxo-5 beta compounds with palladium on calcium carbonate catalyst in ethanol; and 3) stereoselective reduction of appropriate 3-oxo derivatives with potassium tri-sec butylborohydride and tert-butylamine-borane complex. The thin-layer chromatographic, gas-liquid chromatographic, and high performance liquid chromatographic mobilities, and 1H- and 13C-nuclear magnetic resonance spectroscopic data of the four stereoisomers are presented. With this work all the 6-hydroxylated derivatives of lithocholic, deoxycholic, chenodeoxycholic, ursodeoxycholic, and cholic acids in the 5 beta series are now known and have been synthesized. PMID- 1856609 TI - Role of phospholipids in the cytotoxic action of high density lipoprotein on trypanosomes. AB - Host range among the African trypanosomes, protozoa that cause fatal diseases both in humans and livestock, may be, in part, regulated by toxic properties associated with host high density lipoproteins (HDL). High density lipoproteins from hosts resistant (baboon, human) or susceptible (rabbit, rat) to Trypanosoma brucei infection were isolated and their trypanocidal activity was determined in in vitro cell lysis assays. Rabbit and rat HDL were not cytotoxic while baboon and human HDL rapidly lysed trypanosomes within 2 h at 37 degrees C. Analysis of the phospholipid composition of HDL preparations from these species suggested a correlation between trypanocidal activity and low phosphatidylinositol content. Phospholipase digestion of HDL resulted in a loss of trypanocidal activity, indicating the importance of native phospholipids in maintaining this biological activity of HDL. Cell lysis and loss of trypanosome infectivity induced by baboon HDL could be inhibited either by addition of rabbit or rat HDL to the incubation medium or by addition of purified phospholipids, phosphatidylinositol being the most effective inhibitor. Although the mechanism by which HDL lyses trypanosomes remains to be elucidated, these results suggest an important role for phospholipids in determining the specificity of this cytotoxic property of HDL. PMID- 1856611 TI - Neutral and acid retinyl ester hydrolases associated with rat liver microsomes: relationships to microsomal cholesteryl ester hydrolases. AB - We recently reported the presence of a neutral, bile salt-independent retinyl ester hydrolase (REH) activity in rat liver microsomes and showed that it was distinct from the previously studied bile salt-dependent REH and from nonspecific carboxylesterases (Harrison, E. H., and M. Z. Gad. 1989. J. Biol. Chem. 264: 17142-17147). We have now further characterized the hydrolysis of retinyl esters by liver microsomes and have compared the observed activities with those catalyzing the hydrolysis of cholesteryl esters. Microsomes and microsomal subfractions enriched in plasma membranes and endosomes catalyze the hydrolysis of retinyl esters at both neutral and acid pH. The acid and neutral REH enzyme activities can be distinguished from one another on the basis of selective inhibition by metal ions and by irreversible, active site-directed serine esterase inhibitors. The same preparations also catalyze the hydrolysis of cholesteryl esters at both acid and neutral pH. However, the enzyme(s) responsible for the neutral REH activity can be clearly responsible for the neutral REH activity can be clearly differentiated from the neutral cholesteryl ester hydrolase(s) on the basis of differential stability, sensitivity to proteolysis, and sensitivity to active site-directed reagents. These results suggest that the neutral, bile salt-independent REH is relatively specific for the hydrolysis of retinyl esters and thus may play an important physiological role in hepatic vitamin A metabolism. In contrast to the neutral hydrolases, the activities responsible for hydrolysis of retinyl esters and cholesterol esters at acid pH are similar in their responses to the treatments mentioned above. Thus, a single microsomal acid hydrolase may catalyze the hydrolysis of both types of ester.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856612 TI - Inhibition and promotion of cholesterol crystallization by protein fractions from normal human gallbladder bile. AB - Pooled, normal human gallbladder biles were initially separated on a molecular sieving chromatography column to remove soluble mucin glycoproteins as well as high molecular weight proteins (greater than 200,000). The remaining lower molecular weight proteins and other bile components were then examined by lectin affinity chromatography with four different types of lectin. The separated bound fractions were compared for inhibiting and promoting activities with a newly devised sensitive cholesterol crystal growth assay and for differences in electrophoretic patterns on SDS-gels. Protein factors (presumably glycoproteins) were found to have both inhibiting and promoting activities, even in the absence of cholesterol gallstone disease. The promoting effect was indicated by shortened crystal detection times and increases in crystal growth rate; whereas the inhibiting effect was indicated by decreases in crystal growth rate and reductions in the final crystal concentration as determined by the growth assay. Affinity chromatography mitigated the major problems of removing both lipids and pigment from the glycoproteins. In addition, partial purification of bound fractions with potent cholesterol crystal nucleation-altering activity can be obtained by this technique. PMID- 1856613 TI - Head group precursors modify phospholipid synthesis in Schistosoma mansoni. AB - The two predominant phospholipids in schistosomula of Schistosoma mansoni are phosphatidylcholine (PC) and phosphatidylethanolamine (PE) which are found in a molar ratio of 0.52 (PE/PC). The incorporation of four fatty acids (arachidonic, myristic, oleic, and palmitic) and glycerol into phospholipids of schistosomula was measured. In two different media (one containing ethanolamine, the other without), all four fatty acids were predominantly incorporated into PC with a PE/PC ratio of approximately 0.1 in a 90-min label. After a 24-h chase, PC remained the predominant labeled phospholipid but the fatty acid-labeled PE/PC ratio increased slightly, the specific activity of labeled neutral lipids decreased, and the specific activity of labeled PE increased. Glycerol was incorporated with a ratio of 0.55 in the presence of ethanolamine but only 0.19 in its absence. Schistosomula also incorporate fatty acids into phosphatidylmonomethylethanolamine (PMME) and phosphatidyldimethylethanolamine (PDME) at rates intermediate to that into PE and PC in the presence of the respective head group precursor; this incorporation was inhibited by choline. Relative to PC, oleic acid is incorporated into PE, PMME, and PDME at rates higher than for palmitic acid. These results suggest that schistosomula possess acyltransferase(s) with head group specificity and that acyl chains are transferred from neutral lipids to phospholipids over time. PMID- 1856614 TI - Metabolism of D-[3H]threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of glucosylceramide synthesis, and the synergistic action of an inhibitor of microsomal monooxygenase. AB - D-Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) is an effective inhibitor of the glucosyltransferase that makes glucosylceramide. Virtually all of the hundreds of naturally occurring glycolipids are formed from this primary glycolipid, so the inhibitor acts to lower their concentrations by the process of attrition (hydrolytic catabolism). Trials with mice carrying ascites carcinoma cells showed that PDMP could produce a permanent cure in some of the animals and marked prolongation of life in the others (Inokuchi, J., I. Mason, and N.S. Radin. 1987. Cancer Lett. 38: 23-30). In order to maximize the effect, we studied the metabolism of PDMP by labeling it with [3H] on carbon one, using a labeling method that discriminated against the unwanted erythro-isomer. The active enantiomer of the inhibitor (D-) was isolated by chromatography of the camphanate esters, followed by methanolytic cleavage. Examination of the fate of the labeled drug after a single injection showed that it was very rapidly converted to several polar products that were rapidly excreted. The drug penetrated all of the organs readily and a small portion was oxidized at the C-1 position to yield 3H2O. From these findings it appeared likely that the amine is attacked by a mixed function oxidase based on cytochrome P450. This conclusion was confirmed by showing that the tissue levels of PDMP could be greatly elevated, for a much longer time, when the mice were pretreated with piperonyl butoxide or cimetidine. The amount of conversion to polar metabolites was substantially reduced and tissue levels of PDMP were maintained much longer. Analysis of mice injected with one or both drugs showed that piperonyl butoxide augmented the effects of PDMP on ceramide, glucosylceramide, and dihexosylceramide levels, as well as on the activity of glucosylceramide synthase. It is suggested that piperonyl butoxide be used as an adjuvant for the many useful drugs that are inactivated by the P450 system. PMID- 1856615 TI - Isotopic exchange during derivatization of platelet activating factor for gas chromatography-mass spectrometry. AB - One approach to the quantitative analysis of platelet activating factor (PAF, 1-O alkyl-2-acetyl-sn-glycerol-3-phosphocholine; also referred to as AGEPC, alkyl glyceryl ether phosphocholine) is hydrolytic removal of the phosphocholine group and conversion to an electron-capturing derivative for gas chromatography negative ion mass spectrometry. [2H3]Acetyl-AGEPC has been commonly employed as an internal standard. When 1-hexadecyl-2-[2H3]acetyl glycerol (obtained by enzymatic hydrolysis of [2H3]-C16:0 AGEPC) is treated with pentafluorobenzoyl chloride at 120 degrees C, the resulting 3-pentafluorobenzoate derivative shows extensive loss of the deuterium label. This exchange is evidently acid-catalyzed since derivatization of 1-hexadecyl-2-acetyl glycerol under the same conditions in the presence of a trace of 2HCl results in the incorporation of up to three deuterium atoms. Isotope exchange can be avoided if the reaction is carried out at low temperature in the presence of base. Direct derivatization of [2H3]-C16:0 AGEPC by treatment with pentafluorobenzoyl chloride or heptafluorobutyric anhydride also results in loss of the deuterium label. The use of [13C2]-C16:0 AGEPC as an internal standard is recommended for rigorous quantitative analysis. PMID- 1856616 TI - Diagnostic challenge--pigmented lesion of the palate. PMID- 1856617 TI - Compound odontoma in the posterior maxilla: a case report and literature review. PMID- 1856618 TI - Child abuse and neglect: ethical and legal issues for dentistry. PMID- 1856619 TI - A clinico-pathologic presentation. Dentinogenesis imperfecta. PMID- 1856620 TI - A clinico-pathologic presentation. Tooth erosion. PMID- 1856621 TI - Dental institutions in the greater Boston area--4. Harvard University. Post-World War II development of the Harvard School of Dental Medicine. PMID- 1856623 TI - The scheduled associate to partner to buyout process: the SAPB. PMID- 1856622 TI - What is your practice worth? PMID- 1856624 TI - How the purchaser information service helps a dental practice. PMID- 1856625 TI - The regulation by iron of the synthesis of adhesins and cytoadherence levels in the protozoan Trichomonas vaginalis. AB - Levels of adherence of Trichomonas vaginalis to epithelial cells was found to be modulated by iron. Cytoadherence values were greater than or equal to twofold higher for trichomonads grown in a complex cultivation medium supplemented with iron. This increase in adherence levels was specifically mediated by iron; parasites cultured in a low-iron medium in the presence of salts other than iron were unresponsive to changes in adherence levels. Expression of the higher adherence property, by parasites grown first in low-iron medium followed by supplementation with iron, was a function of time, and the extent of cytoadherence was proportional to the concentration of iron added to the medium. Lactoferrin, an important iron source for trichomonads at the site of infection, elevated adherence of the parasite to epithelial cells, demonstrating the likely in vivo modulation of adherence by iron. The alteration of levels of adherence caused by iron was determined to be a reflection of gene expression of previously characterized trichomonad adhesins. Parasites grown under iron-replete conditions had higher quantities of surface-exposed adhesins, and this was a result of increased synthesis of adhesins. Actinomycin D and alpha-amanitin prevented expression of adhesin molecules, which resulted in decreased cytoadherence, showing that adhesin synthesis was dependent on gene transcription. Data indicated that genes encoding the four trichomonad adhesins are coordinately regulated by iron. PMID- 1856626 TI - Alteration of the natural killer repertoire in H-2 transgenic mice: specificity of rapid lymphoma cell clearance determined by the H-2 phenotype of the target. AB - The mechanism behind natural tumor resistance conveyed by a H-2Dd transgene to C57Bl/6 (B6) mice was investigated. Transgenic D8 mice were more efficient than control mice in natural killer (NK) cell mediated rapid elimination of intravenously inoculated radiolabeled lymphoma cells of B6 origin, such as RBL-5. There was no difference between D8 and B6 mice when elimination of YAC-1 targets was monitored. The effect of the transgene on the NK repertoire was related to the H-2 phenotype of the target: the differential elimination of RBL-5 lymphoma cells in D8 and B6 mice was not seen when a H-2 deficient variant of this line was used (efficiently eliminated in both genotypes), nor was it seen with a H-2Dd transfectant (surviving in both genotypes). The data show that a MHC class I transgene can directly control natural killing in vivo by altering the repertoire rather than the general levels of NK activity. Since the NK mediated elimination seen after introduction of a novel gene in the host was neutralized by introducing the same gene (H-2Dd), but not an unrelated class I gene (H-2Dp), in the tumor, the data support the concept of NK surveillance against missing self. This combined transgenic/transfectant system may serve as a tool for a molecular dissection of the interactions between NK cells and their targets in vivo. PMID- 1856627 TI - Differential disease restriction of Moloney and Friend murine leukemia viruses by the mouse Rmcf gene is governed by the viral long terminal repeat. AB - Neonatal CxD2 (Rmcfr) and Balb/c (Rmcfs) mice inoculated with Moloney murine leukemia virus (M-MuLV) exhibited approximately equivalent time course and pathology for disease. CxD2 mice showed only slightly reduced presence of Moloney mink cell focus-forming virus (M-MCF) provirus as seen by Southern blot analysis compared to Balb/c mice. This lack of restriction for disease and spread of MCF was in sharp contrast to that seen for CxD2 mice inoculated with Friend murine leukemia virus (F-MuLV), where incidence of disease and propagation of MCFs were severely restricted, as previously reported. Inoculation of CxD2 mice with FM MuLV, a recombinant F-MuLV virus containing M-MuLV LTR sequences (U3 and R), resulted in T cell disease of time course equal to that seen in Balb/c mice; there also was little restriction for propagation of MCFs. This indicated that presence of the M-MuLV long terminal repeat (LTR) was sufficient for propagation of MCFs in CxD2 mice. Differing restriction for F-MuLV vs. M-MuLV in CxD2 mice was explained on the basis of different "MCF propagator cells" for the two viruses. It was suggested that cells propagating F-MCF (e.g., erythroid progenitors) are blocked by endogenous MCF-like gp70env protein, whereas cells propagating M-MCF (e.g., lymphoid) do not express this protein on their surface. F-MuLV disease in CxD2 mice was greatly accelerated when neonates were inoculated with a F-MuLV/F-MCF pseudotypic mixture. However, F-MCF provirus was not detectable or only barely detectable in F-MuLV/F-MCF-induced tumors, suggesting that F-MCF acted indirectly in induction of these tumors. PMID- 1856628 TI - Early separation of B and T lymphocyte precursors in chick embryo. AB - Embryonic chimeras were used to demonstrate an early separation of chicken T and B cell precursors. Genetically polymorphic cell surface antigens, Bu-1 and Ov, which are expressed on cells of the B and T lineage, respectively, are useful markers in adoptive cell transfer studies. Allelic products Bu-1a and Bu-1b can be detected with monoclonal antibodies (mAbs) L22 and 11G2, respectively, and the Ov antigen with mAb 11A9. Chimeric chickens were constructed by reconstituting irradiated 14-d Ov- H.B19 embryos with the sorted Bu-1+ or Bu-1- fractions of spleen cells from age-matched H.B19 Ov+ embryos. Chimeras were analyzed, 3-4 wk after hatching, for the presence of Ov+ cells in the bursa, thymus, spleen, and peripheral blood lymphocytes. T cell precursors giving rise to thymocytes and peripheral T cells were present only in the Bu-1-, but not in the Bu-1+, fraction. We previously demonstrated that, in contrast, all B cell precursors in spleen from 14-d embryos are exclusively present in the Bu-1+ fraction. We also analyzed the immunoglobulin light chain gene rearrangement in these populations by polymerase chain reaction. We show here that VJ recombination occurs in the Bu 1+, but not in the Bu-1-, fraction of spleen. These data demonstrate an early commitment to the B cell lineage, which occurs before the colonization of the bursa of Fabricius. Segregation of B cell precursors from the other hemopoietic precursors, and consequently separation of T and B cell precursors, occurs before the colonization of the primary lymphoid organs. PMID- 1856629 TI - Cross-species bone marrow transplantation: evidence for tolerance induction, stem cell engraftment, and maturation of T lymphocytes in a xenogeneic stromal environment (rat----mouse). AB - Transplantation of untreated F344 rat bone marrow into irradiated B10 mouse recipients (non-TCD F344----B10) to produce fully xenogeneic chimeras resulted in stable xenogeneic lymphoid chimerism, ranging from 82% to 97% rat. Survival of animals was excellent, without evidence for GVH disease. The specificity of tolerance which resulted was highly donor-specific; MHC disparate third party mouse and rat skin grafts were promptly rejected while donor-specific F344 grafts were significantly prolonged (MST greater than 130 days). Multi-lineage rat stem cell-derived progeny including lymphoid cells (T- and B-lymphocytes), myeloid cells, erythrocytes, platelets, and natural killer (NK) cells were present in the fully xenogenic chimeras up to 7 months after bone marrow transplantation. Immature rat T-lymphocytes matured and acquired the alpha/beta T-cell receptor in the thymus of chimeras in a pattern similar to normal rat controls, suggesting that immature T-lymphocytes of rat origin could interact with the murine xenogeneic thymic stroma to undergo normal maturation and differentiation. This model may be useful to study the mechanisms responsible for the induction and maintenance of donor-specific transplantation tolerance across a species barrier. PMID- 1856631 TI - Endogenously synthesized peptide with an endoplasmic reticulum signal sequence sensitizes antigen processing mutant cells to class I-restricted cell-mediated lysis. AB - The HLA-A2-positive human mutant cell line T2 is not lysed by influenza virus specific HLA-A2-restricted cytotoxic lymphocytes after virus infection. However, lysis does occur when cells are incubated with the antigenic influenza matrix protein-derived peptide M57-68. To examine the nature of this defect, T2 cells were transfected with two different plasmids. One plasmid encoded the peptide M57 68, and the other encoded the same peptide preceded by an endoplasmic reticulum translocation signal sequence. Mutant T2 cells expressing the M57-68 peptide without the signal sequence were not susceptible to lysis by M57-68-specific HLA A2-restricted cytotoxic T lymphocytes, whereas T2 cells expressing the M57-68 peptide plus signal sequence were lysed effectively. Lysis of parental T1 cells with either plasmid was equally effective. These results suggest that the T2 mutant cells are defective in the transport of antigenic peptides from the cytosol into the secretory pathway. PMID- 1856630 TI - Accumulation of adoptively transferred adherent, lymphokine-activated killer cells in murine metastases. AB - While close contact between lymphokine-activated killer (LAK)/adherent, lymphokine-activated killer (A-LAK) cells and tumor cells is believed to be a prerequisite for initiating the events leading to tumor cell lysis, clear evidence for the ability of these effector cells to infiltrate tumors or tumor metastases in vivo still has to be obtained. In the present study, we report that a significant fraction of adoptively transferred A-LAK cells, labeled with fluorochromes for identification, accumulates in lung and liver metastases of the B16 melanoma, the MCA 102 sarcoma and the Lewis lung carcinoma lines. Thus, 5- to 10-fold higher numbers of A-LAK cells were found in the malignant lesions compared to the surrounding normal tissue. The infiltration seemed very heterogeneous after intravenous injection of moderate numbers of A-LAK cells (15 x 10(6)). However, after adoptive transfer of 45 million A-LAK cells, an A-LAK cell/tumor cell ratio higher than 1:1 in most metastases was observed. Surprisingly, approximately 5% of the lung metastases seemed totally resistant to infiltration even though neighboring metastases were highly infiltrated. While substantial infiltration of lung metastases was seen after i.v. injection, significant infiltration of liver metastases was seen only after intraportal injection of the A-LAK cells indicating impaired traffic of intravenous injected A-LAK cells through the lung capillaries. These results present direct evidence that A-LAK cells, upon a proper route of administration, have the potential to migrate to and heavily infiltrate metastases from murine tumors of different origin. PMID- 1856633 TI - Description of the abrasion furrow in hanging. PMID- 1856632 TI - Further discussion on discussion of "Hair analysis for drugs of abuse". PMID- 1856634 TI - Estimating the second breath alcohol measurement from the first: a model refinement. PMID- 1856636 TI - Chemicals reacting with various forms of hemoglobin: biological significance, mechanisms, and determination. AB - The clinical chemistry of various forms of hemoglobin occupies a large fraction of the total activities of hospital and forensic science laboratories. Some of the potential pitfalls are reviewed here along with an account of the accidental discovery of two novel chemical forms. Human or mouse red blood cells were exposed to excess sodium nitrite to convert the intracellular pigment to methemoglobin. When these were subsequently incubated in Krebs-Ringer-phosphate glucose medium, pH 7.4 at 37 degrees C under nitrogen and in the presence of various concentrations of methylene blue, a blood pigment was generated in high yield which had unique properties. In lysates, the pigment was stable in air, and it could be maintained in liquid nitrogen for as long as a year without deterioration. The pigment had properties different from those of oxyhemoglobin, deoxyhemoglobin, methemoglobin, or carboxyhemoglobin. After separation by isoelectric focusing, the pigment gave a strong signal on electron paramagnetic resonance (EPR) spectroscopy. The other forms of hemoglobin given above are EPR silent. The pigment was eventually identified as the nitrosylated valency hybrid species, (alpha 2+ beta 3+)2(NO)2. The corresponding species, (alpha 3+ beta 2+)2(NO)2, has similar properties. These species apparently owe their unusual stability in air to the presence of the oxidized subunits in the same tetramer. PMID- 1856635 TI - Genetic markers in human bone: II. Studies on ABO (and IGH) grouping. AB - A combination absorption-elution, two-dimensional absorption-inhibition procedure was used to determine the ABH antigen composition of a series of human bone specimens of known ABO type that had been aged up to nine months under dry and humid conditions at ambient temperature, 37 degrees C, and 56 degrees C; at ambient temperature in dry and wet soil; and buried in soil outdoors. Grouping data for the separate elution and inhibition testing, as well as for the combination procedure, are given. The combination method was found to be a highly reliable procedure for bone tissue ABH typing. Some data on microbial contaminants of human bone specimens aging in soil, and their effects on ABH typing results, are presented. No direct correlation between the properties of microbial contaminants and specific changes in the ABH antigenic composition of aging bone tissue specimens could be ascertained. Data on IGH antigen determination and on the quantitation of immunoglobulin G (IgG) in human bone tissue extracts indicated that immunoglobulin levels were typically too low to expect routinely successful Gm antigen testing results. However, these factors can sometimes be determined in fresh bone tissue extracts, particularly if the extracts are concentrated. PMID- 1856637 TI - Site-dependent postmortem changes in blood cocaine concentrations. AB - When a forensic toxicologist interprets postmortem blood cocaine findings he usually must make assumptions regarding perimortem drug concentrations. In-vitro studies have shown that cocaine rapidly hydrolyzes in unpreserved blood, particularly at elevated temperatures. However, other studies have demonstrated site-dependent postmortem release of some drugs from tissue stores accompanied by increases in drug concentrations in the blood. This study was undertaken to investigate whether blood cocaine concentrations change in the body during the postmortem interval and, if so, to measure the direction and magnitude of the changes. In medical examiner cases in which scene investigation suggested that the decreased was a cocaine user, blood samples were collected as soon after death as possible. At autopsy, a second set of samples was collected. Analysis of paired samples by gas chromatography/mass spectrometry (GC/MS) revealed dramatic differences in the cocaine concentration. The magnitude and direction of the change appears to be site dependent. Usually, but not invariably, cocaine concentration in subclavian vein blood decreases while that in heart, aorta, and femoral vein blood increases during the interval between death and autopsy. The findings emphasize the danger inherent in attempting to estimate the concentration of cocaine in blood at the time of death from postmortem data. PMID- 1856638 TI - Poppy seed ingestion as a contributing factor to opiate-positive urinalysis results: the Pacific perspective. AB - The possible contribution of poppy seed foods to positive opiate urinalysis results, especially from foods available in the Pacific Rim area, has recently become an issue for the U.S. Army Forensic Toxicology Drug Testing Laboratory in Hawaii. To assess the likelihood of this possible contribution, seven different poppy seed food products were consumed by male and female volunteers, and urine specimens were collected at time increments up to either 24 or 72 h. Specimens were evaluated for opiates using Roche Abuscreen radioimmunoassay (RIA), and all RIA positive specimens were analyzed for morphine and codeine using gas chromatography/mass spectrometry (GC-MS). Poppy seed cake, bagels, muffins, and rolls did not contain sufficient quantities of poppy seeds to give rise to opiate positive specimens by U.S. Department of Defense (DOD) GC-MS cutoff levels (morphine = 4000 ng/mL, codeine = 2000 ng/mL), although a number of specimens were positive by National Institute on Drug Abuse (NIDA) cutoff levels (morphine and codeine = 300 ng/mL). However, ingestion of poppy seed streusel or Danish pastry led to confirmed morphine and codeine positive specimens, irrespective of the use of DOD or NIDA confirmation cutoff values. In addition, significant amounts of codeine were observed in a number of these specimens. These findings argue against the unqualified application of previously published quantitative guidelines for eliminating poppy seed ingestion as a possible cause for a positive opiate urinalysis result. PMID- 1856639 TI - Alleged brain damage, diminished capacity, mens rea, and misuse of medical concepts. AB - As focus on the insanity defense diminishes, defendants may place emphasis on a lack of knowing or purposeful behavior in order to negate a criminal charge. This use of a mens rea defense in accord with Model Penal Code principles is exemplified by the current New Jersey statute. Such a defense may result in a lesser charge or a finding of not guilty. In addition to reviewing applicable law, this report presents a sex offense case in which remote brain damage was invoked as a purported basis for incapacity to formulate the required intent; the study also raises the issue of the inappropriate or questionable use of medical principles, a practice that diminishes professional credibility in the courts and in the community. PMID- 1856640 TI - The Tarasoff dilemma in criminal court. AB - The duty to protect, or Tarasoff duty, has been conceptualized as arising solely in the context of a clinical setting. A recent California Supreme Court ruling in People v. Clark adds legal, clinical, and ethical dilemmas to the oftentimes contentious Tarasoff issue. Though the Tarasoff issue is but a minor legal point in Clark, a possible consequence of Clark is that a Tarasoff warning could be deemed nonconfidential and admissible in a criminal trial. Psychotherapists could therefore be testifying in criminal courts as prosecution witnesses. While the possibility of a chilling effect on patients' disclosure of violent ideation in the context of psychotherapy first caused apprehension after the California Supreme Court's 1976 decision in Tarasoff v. Regents of the University of California, this same Court's ruling in People v. Clark some 14 years later may ensure that this fear finally becomes realized. PMID- 1856641 TI - Interpretation of unusual wounds caused by firearms. AB - The interpretation of the range of fire of gunshot wounds requires coordination of information and observations from the autopsy surgeon, scene investigator, and laboratory analyst. Opinions based on incomplete information often lead to misinterpretation of the wound. The effects of interposed targets such as clothing, windows, and body parts are discussed. Case examples are given for interposed targets that cause confusing patterns and even lead to misidentification of the points of entrance and exit of the projectile in the body. The splitting of tissue in areas of bony prominence can be mistaken for evidence of discharge of a firearm at close range. PMID- 1856642 TI - The eyes of child abuse victims: autopsy findings. AB - The authors studied 77 pairs of eyes removed from children who had died of suspected child abuse. Forty-seven of the cases had retinal hemorrhages. Those showing retinal hemorrhages were younger children and had fewer other stigmata of child abuse. Hemorrhages are more likely to occur in cases where the child was shaken or swung than in those with severe direct head trauma. The authors recommend that examination of the eyes be included in the autopsies of all small children who died without an obvious cause of death. Experience in both processing and reading of ocular material is necessary for reliable results. PMID- 1856643 TI - Comparison of insect species associated with decomposing remains recovered inside dwellings and outdoors on the island of Oahu, Hawaii. AB - A comparison of insects collected from 35 cases of decomposing remains on the island of Oahu, Hawaiian Islands (14 from indoor situations and 21 from outdoors), yielded a total of 22 species of insects in 3 orders and 12 families. Of these, five species were recovered in both indoor and outdoor situations. Remains recovered indoors had a greater variety of Diptera larvae associated with them, while remains discovered outdoors had a greater variety of Coleoptera species present. Some species of insects were restricted to remains discovered indoors, while others were found only associated with remains in outdoor situations. Knowledge of the species of insects associated with different habitats may serve to provide information concerning the history of the remains. PMID- 1856644 TI - Alcohol addiction of methamphetamine abusers in Japan. AB - Fifty-eight methamphetamine (MAMP) abusers were surveyed to demonstrate the types of nature of MAMP abuse. In-depth interviews using psychophysiological techniques assessed the subjects to be truthful or deceptive about their abuse histories. Research diagnostic criteria determined the subjects clinical symptoms. The results show that three factors characterize MAMP abuse: significant correlation was found between the years of abuse; the manifestation of somatic or mental disorders or both, and alcohol (Alc) addiction. MAMP abusers who were nondrinkers or light drinkers developed a tendency to dislike Alc after MAMP abuse, while there was no change in Alc consumption in heavy drinkers. The findings suggest that the combined abuse of MAMP and Alc aggravates somatic and mental disorders and that Alc plays an important role in the fatal effect of MAMP, especially from small doses. This provides support for the synergistic effects between MAMP and Alc. Coadministration of MAMP and Alc appears to produce long-acting and more complicated changes in the brain's neurotransmitter function. PMID- 1856645 TI - Stature- and age-related bias in self-reported stature. AB - The use of reported stature, especially self-reported stature such as on a driver's license, as a proxy for measured stature is necessary when measured stature is unavailable, for example, in matching data calculated from skeletal remains with data for missing persons. The accuracy of self-reported stature for older persons and especially for tall and short people is not well ascertained. Examination of published reports provides evidence that beginning at age 45, people compound their stature overestimation by an additional amount related to age (women by twice the amount of men). Analysis of anthropometric data from 8000 U.S. Army personnel indicates that the amount of general overestimation of stature by men is 2 1/2 times greater than that by women. Neither tall men nor tall women underestimate their stature, but men in the upper third of the stature range, and women in the upper 10%, self-report their stature with greater accuracy. No trends in accuracy are apparent in the remainder of the stature spectrum for men or women. PMID- 1856646 TI - Maxillary suture obliteration: a visual method for estimating skeletal age. AB - The purpose of this study was to develop a method of estimating the age of an individual based on obliteration of the four maxillary (palatal) sutures. A sample of 186 individuals of known age, race, and sex were examined. It was found that males of both races (black and white) exhibit more suture obliteration than females at the same age. During the early adult years, maxillary suture obliteration progresses at nearly the same rate in both sexes; however, the age of old individuals may be greatly overestimated using this method. Although this method cannot be used for exact estimates of individual age, it is valuable in establishing the age range, sorting commingled remains, and estimating skeletal age when only the maxilla is present. PMID- 1856647 TI - Age estimation using the racemization of amino acid in human dentin. AB - This study was made to improve the validity of age estimation from teeth using amino acid racemization. The correlation between actual age and the D/L ratio of aspartic acid was investigated by analyzing not only the total amino acid but also its fractionated substances, insoluble collagen and soluble peptide. The coefficient values of correlation between the D/L ratio and actual age in adult lower central incisors were 0.996 (sigma = +/- 1.0 year) for the total amino acid, 0.988 (sigma = +/- 1.8 years) for insoluble collagen, and 0.997 (sigma = +/ 0.9 years) for soluble peptide. The corresponding figures in adult first premolars were 0.991 (sigma = +/- 1.6 years), 0.988 (sigma = +/- 1.9 years), and 0.994 (sigma = +/- 1.4 years), respectively. The reactive velocity of aspartic acid racemization was highest for soluble peptide in both the lower central incisors and first premolars and approximately three times as rapid as that for total amino acid. As a result, age estimated from the analysis of soluble peptide was most accurate. The velocity for insoluble collagen was slightly lower than that for total amino acid. Age estimation was attempted from the teeth of an unknown body. These results suggest that the analyses, not only of total amino acid in dentin but also of its fractionated and extracted substances, can lead to higher reliability in age estimation. Soluble peptide, in particular, has been found to be most effective. PMID- 1856648 TI - Differentiation of hydrocephalic calf and human calvariae. AB - Occasionally, partial calvariae of hydrocephalic calves are found in forensic contexts and mistakenly identified as human. Such specimens can be properly identified through immunological assessment of associated soft tissue, microscopic analysis of associated hair, and morphological comparison with documented museum specimens. Morphological comparison should focus on the form of the occiput, supraorbital grooves, and bulbous vault and presence of coronal processes. PMID- 1856649 TI - Inaccuracy of height information on driver's licenses. AB - Height is an important variable in identification. In cases involving decreased individuals, height is measured directly on the corpse or estimated from the skeleton. This postmortem measurement or estimation is then compared with antemortem records, usually the driver's license. The accuracy of the license information, however, has been questioned. To assess the accuracy of driver's license information, volunteers' statures were measured, and then these figures were compared with those printed on the subjects' licenses. Even in our comparatively young, well-educated sample, the license height was significantly greater than the measured height. Some inaccuracies may be caused by failure to update license information when new licenses are issued, but some inaccuracies may be from personal deception. The implications of these results for forensic anthropology cases are discussed. PMID- 1856650 TI - Laboratory investigation of deaths due to anaphylaxis. AB - To establish a useful laboratory protocol to investigate possible cases of fatal anaphylaxis, we measured mast-cell-derived tryptase levels and allergen-specific immunoglobulin E (IgE) antibody levels in sera obtained prior to or within 24 h after death from 19 anaphylaxis victims. Elevated serum tryptase levels (range = 12 ng/mL to 150 micrograms/mL) were found in nine of nine Hymenoptera sting fatalities, six of eight food-induced fatalities, and two of two reactions to diagnostic therapeutic agents. Tryptase levels were normal (less than 10 ng/mL) in 57 sequential sera obtained postmortem from six control patients. Tryptase could not be measured in pleural or pericardial fluids for technical reasons. Serum IgE antibodies were elevated in five of the nine Hymenoptera sting fatalities and in eight of the eight fatal food reactions; assays were unavailable for the two diagnostic/therapeutic agents. If elevated, the victim's serum IgE antibodies to food could be used to identify allergens in uneaten portions of foods consumed shortly before the anaphylactic event. IgE antibodies were moderately stable during storage in a variety of anticoagulants at room temperature for up to 11 weeks. Elevated mast-cell-derived tryptase levels in postmortem sera reflect antemortem mast cell activation and may be used as a marker for fatal anaphylaxis. If assays are available for IgE antibodies to relevant allergens, such assays provide evidence for antemortem sensitization; these assays may be modified to identify allergens in foods consumed by victims of food-induced anaphylaxis. PMID- 1856651 TI - Polymorphisms of the enzyme systems galactose-1-phosphate uridyltransferase (GALT) and esterase D (EsD) in the province of Cadiz, southern Spain. AB - Galactose-phosphate uridyltransferase (GALT) and esterase D (EsD) phenotypes were determined by isoelectric focusing in ultrathin-layer polyacrylamide gel (PAGIF) for 406 healthy subjects randomly chosen and residing in the province of Cadiz, in Southern Spain. The following gene frequencies were observed: for GALT, GALT1 = 0.952 970 3 and GALT2 = 0.047 029 71; for EsD, EsD1 = 0.895 320 2, EsD2 = 0.094 827 59, and EsD5 = 0.009 852 21. PMID- 1856652 TI - Corrections for age in estimating older adults' stature from long bones. AB - Stature estimates based on long bone measurements require a correction factor to compensate for stature decrease in older people. Such a correction should exclude the effect of any secular trend in stature and reflect the age at which stature begins to decrease, sex differences, and the increasing rate of change with age. Stature correction which meet these requirements for ages 46 through 85, based upon two recent large-scale longitudinal anthropometric studies, are provided in tabular form. PMID- 1856653 TI - Cerebral tissue pulmonary embolization due to head trauma: a case report with immunohistochemical confirmation. AB - Pulmonary embolization of cerebral tissue as the result of severe head trauma is an uncommon, if not rare, phenomenon, and few cases have been reported in the literature. The authors discuss the case of a 51-year-old male who died six days after suffering extensive head trauma in a motor vehicle collision. At autopsy, white-gray emboli were found in several subsegmental pulmonary arteries. The results of histologic examination with the hematoxylineosin stain gave the impression that the emboli were necrotic cerebral tissue; however, routine special stains for neural tissue produced inconclusive results. Immunohistochemical staining of the emboli with monoclonal mouse anti-human neurofilament protein (Dako Corp., Carpinteria, California) confirmed the cerebral nature of the emboli. To the authors' knowledge, this is the first reported case of pulmonary embolization of cerebral tissue confirmed by immunohistochemistry. PMID- 1856654 TI - Cocaine, fetal loss, and the role of the forensic pathologist. AB - Adverse obstetrical outcomes are often associated with maternal cocaine use. These have included intrauterine growth retardation, abruptio placentae, and an increased incidence of spontaneous abortion and pre-term labor. This report details the case of an 18-week-gestation fetus recovered from a sewage treatment plant. A brain specimen was positive for cocaine. With the present epidemic of cocaine abuse, it is important for the forensic pathologist to seek toxicologic evidence of cocaine in all suspicious fetal and neonatal deaths. PMID- 1856655 TI - Fatal acetaminophen poisoning with evidence of subendocardial necrosis of the heart. AB - The authors describe a case of fatal acetaminophen overdose which occurred in a 16-year-old female. Her serum acetaminophen concentration 11.5 h postingestion was 154 mg/L. Antidotal therapy was unsuccessful, and after 9 days she died. Autopsy findings included centrilobular zonal liver necrosis, acute proximal renal tubular necrosis, and diffuse alveolar pulmonary damage. Her heart was transplanted into a young woman with congenital heart disease. The recipient expired 14 days after the transplant as a result of sepsis complicating bowel ischemia. The transplanted heart showed extensive subendocardial myocyte necrosis related to acetaminophen toxicity and not rejection. PMID- 1856656 TI - Postmortem determination of the biological distribution of formic acid in methanol intoxication. AB - Two 25-year-old men were fatally intoxicated with methanol. The formic acid levels in their blood, urine, and organs were determined postmortem by headspace gas chromatography. The postmortem concentrations of formic acid in the two patients were the following: 0.32 and 0.23 mg/mL in blood, 2.27 and 0.47 mg/mL in urine, 0.11 and 1.17 mg/g in the brain, 0.54 and 0.51 mg/g in the liver, and 0.13 and 1.19 mg/g in the kidneys. The total amounts of formic acid in the gastric contents were 108 and 23.2 mg. PMID- 1856657 TI - Individualization and enamel histology: a case report in forensic anthropology. AB - The cranium of a native Indian child about six years old was found in 1979 near Taseko River, British Columbia, Canada. While the remains matched the report of a child missing for eight years in terms of race, age at death, locale, and elapsed time since death, the cranium and dentition were basically unidentifiable because of the claimed lack of medical or dental history. There was no dental work, and the parents were unknown or dead. We report the presence, in the dental enamel of the primary and secondary dentition, of stress markers, termed striae of Retzius, whose locations correspond well with anecdotal reports and recently discovered medical records which describe the timing of specific episodes of stress. The enhanced probability of personal identification from dental histological stress markers is evaluated. PMID- 1856658 TI - Bones, blood, pellets, glass, and no body. AB - A man was found guilty of killing his wife, although her body was never found. The case centered on her car, which contained fragments of bone, glass, shotgun pellets, and dried blood. Deoxyribonucleic acid (DNA) fingerprinting techniques were used to establish the decedent's identity. Examination of the bone fragments revealed that they were from the skull. These two pieces of information, added to other evidence, proved that the defendant's wife had received a fatal injury in her car, and a guilty verdict was rendered. PMID- 1856660 TI - Inheritors of the future. PMID- 1856659 TI - Bone fragments a body can make. AB - Data obtained from various analytical techniques applied to a number of small bone fragments recovered from a crime scene were used to provide evidence for the occurrence of a fatality. Microscopic and histomorphometric analyses confirmed that the fragments were from a human skull. X-ray microanalysis of darkened areas on the bone fragments revealed a chemical signature that matched the chemical signature of a shotgun pellet recovered at the scene of the crime. The above findings supported the deoxyribonucleic acid (DNA) fingerprint evidence which, along with other evidence, was used to convict a man for the murder of his wife, even though her body was never recovered. PMID- 1856661 TI - Constitutional amendment campaign. Not now. PMID- 1856662 TI - Conditioning. PMID- 1856663 TI - Practical geriatrics. PMID- 1856664 TI - Contrary principles. PMID- 1856665 TI - American medicine through another looking glass. PMID- 1856666 TI - Chiropractic caveats rebuttal. PMID- 1856667 TI - Innovation in indigent health care. Tallahassee Primary Care Project. PMID- 1856668 TI - EMS-C system development. Update for Florida physicians. PMID- 1856669 TI - Child and adolescent suicide. AB - This review of recent literature on child and adolescent suicide provides a comprehensive view of this alarming social problem which claims over 2,000 lives per year in the United States. It is directed at pediatricians, family physicians and other practitioners to alert them to the warning signs. PMID- 1856670 TI - Bicycle safety. What's new in '92? AB - There are over 100 million bicycle riders in America, according to the National Safety Council, and in the last two years more than 1.25 million accidents have been reported. About 77% of these accidents occurred among children under 15 years old. Nearly 44% of reportable injuries were in the 5-14 year old age group and 30% occurred among children under five years of age, according to the National Center for Health Statistics. PMID- 1856671 TI - Do electronic fetal heart rate monitors improve delivery outcomes? AB - Since the development of electronic fetal heart rate monitors, there has been considerable debate over observable benefits of their use. Early uncontrolled observational studies and retrospective case studies suggested that fetal distress detected by monitoring could help lower both intrapartum and neonatal death rates, serving a utility among high risk deliveries. However, these studies were conducted at a time when neonatal intensive care units and advancing technologies were also beginning to markedly influence perinatal mortality. Randomized clinical trials of the past 10 years have compared electronic monitoring to routine periodic auscultation and have consistently failed to demonstrate a statistically significant difference in either the perinatal mortality rate or the outcome of high risk pregnancies. A few of these studies, however, did report a lower incidence of neurological complications within the monitored deliveries. The latest research, though, has failed to substantiate any long-term neurological benefits from electronic monitoring. PMID- 1856672 TI - Innovations in diagnostic imaging. Magnetic resonance angiography and color image display. PMID- 1856673 TI - A guide to interpreting single locus profiles of DNA mixtures in forensic cases. AB - Analysis of a mixed body fluid crime sample by means of a single locus DNA probe may give rise to several bands. If a suspect is found to have a profile which matches two of the bands, then the evaluation of the evidential strength requires careful analysis. This paper describes the analysis of two relatively simple case examples. It is intended that the principles of the interpretative process will provide a guide to caseworkers who may encounter similar cases. The extension of the treatment to more complex cases should be clear. PMID- 1856674 TI - Calculating the frequency of occurrence of a blood type for a 'random man'. AB - A scheme is offered for the calculation of blood group frequencies for mixed racial populations. The issue of which population to model is discussed. Consideration is also given to the racial composition of the desired survey and to the rule of mutual independence. The scheme can in many cases be applied to existing data. PMID- 1856676 TI - Biochemical and genetic studies on the function of, and relationship between, the PGI1- and CDC30-encoded phosphoglucose isomerases in Saccharomyces cerevisiae. AB - Isoelectric focusing was used to compare the complement of phosphoglucose isomerase isoenzymes in a wild-type strain of Saccharomyces cerevisiae and in a strain with a deletion in the PGI1 structural gene. Deletion of the PGI1 gene did not result in the absence of the high-Km isoenzyme I but the low-Km isoenzyme II was absent. Hence, the isoenzymes must be the products of two genes. If PGI1 were the sole structural gene its deletion would result in the disappearance of both isoenzymes. After a temperature shift-up a cdc30-bearing strain had cell cycle arrested and contained only 8% of the polysaccharide in the wild-type. Phosphoglucose isomerase is required for the synthesis of fructose 6-phosphate (F6-P), a precursor of the cell wall components chitin and mannoprotein ('mannan'), which are a polysaccharide and contain polysaccharide, respectively. Since the cdc30 mutation confers a temperature-sensitive phosphoglucose isomerase, the likely explanation for cell cycle arrest caused by this mutation is that the defective phosphoglucose isomerase results in a reduction of F6-P and hence an inability to synthesize the mannan and chitin needed for cytokinesis and cell separation. Revertants of a pgi1-1 bearing strain were selected for their ability to grow on glucose at 25 degrees C and this yielded a number of different phenotypes. Amongst the isolates was a strain which had undergone an intragenic reversion at the pgi1 locus, designated pgi1-1,100. This mutation permits growth and cell division at 25 degrees C but results in cell cycle arrest at 36 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856675 TI - Post-mortem cooling of the human head: an infrared thermology study. AB - The post-mortem cooling of the human head, over the first fifteen hours after death, was measured by infrared thermology. A detailed temperature map of the head and face was obtained by the use of image processing techniques and the cooling behaviour of twelve preselected facial features was observed. The two main findings of the study were a difference in cooling pattern between the upper and the lower part of the head, and a consistency in the cooling pattern of the lower part of the head in all the cases studied. A comparison of various model fits to the raw data was undertaken and the "best" bodies, models and features were determined on a statistical basis. The formula that best fitted the raw data was a novel double application of Newton's law. The features with the least error in data fitting were the chin and zygoma; that with the most error was the mouth. PMID- 1856677 TI - Expression and secretion of staphylococcal nuclease in yeast: effects of amino terminal sequences. AB - Staphylococcus aureus nuclease A hybrid genes, encoding proteins OmpA-nuclease, lipo-nuclease and Pin-nuclease, were cloned downstream of the yeast GAL10 inducible promoter. OmpA-nuclease and lipo-nuclease contain the mature staphylococcal nuclease sequence preceded by the Escherichia coli OmpA and lipoprotein signal sequences, respectively, whereas Pin-nuclease lacks a defined signal sequence at its amino terminus. We found that: (a) the nuclease gene products synthesized in yeast are active, but they do not affect cell growth; (b) OmpA-nuclease and lipo-nuclease are partially processed and constitute approximately 1.0-1.5% of the yeast cell protein; (c) OmpA and lipoprotein signal sequences function similarly in secretion, allowing 35-40% of the processed nuclease to be translocated into the yeast periplasm; and (d) Pin-nuclease, which lacks hydrophobic sequences at its amino-terminus, is accumulated at a level tenfold lower than the hybrid proteins that do contain signal sequences. Nevertheless, 50% of the enzyme activity of Pin-nuclease in yeast is localized in the periplasmic space. PMID- 1856678 TI - The effect of temperature shifts on protein synthesis by the psychrophilic bacterium Vibrio sp. strain ANT-300. AB - In the psychrophilic bacterium Vibrio sp. strain ANT-300, the temperature-related characteristics of protein synthesis in cells grown at 0 degrees C differed from those of cells grown at 13 degrees C. Cells grown at 0 degrees C and 13 degrees C transported amino acids at the same rates, dependent on the temperature at which rates were measured. The rates of protein synthesis in extracts of cells grown at 0 degrees C and at 13 degrees C differed, as a result of the changes in the properties of the soluble fraction involved in protein synthesis. Concurrently, levels of more than 24 polypeptides in the soluble fraction changed considerably. These results suggest that the difference in temperature dependence of protein synthesis in cells grown at various temperatures may be brought about by specific changes in the levels of a small number of polypeptides (less than 15% of the total number of proteins detected by silver-staining) in response to a change in temperature. PMID- 1856679 TI - Characterization of Fonsecaea pedrosoi melanin. AB - The constituents of the melanin complex from mycelial forms of Fonsecaea pedrosoi were partially characterized. The pigment was mainly accumulated on large alkali extractable, electron-dense cytoplasmic bodies (melanosomes) and, apparently, on the outer layer of the cell wall as external deposits within verrucose outgrowths. Using electron microscopy and Thiery's periodate/thiosemicarbazide/silver proteinate staining method, glycogen-like particles were also detected at the periphery of the cells. Melanin constituents comprised aromatic and aliphatic/glycosidic structures with a predominance of the latter. Infrared spectra showed the presence of hydroxyl, carbonyl and carboxyl groups. The aliphatic/glycosidic moiety consisted of fatty acids and polysaccharides with protein, in a ratio protein/polysaccharide 1:15. Rhamnose, mannose, galactose and glucose (in the ratio 1:2:4:3.5) were the constituents of the polysaccharide. Lipid components included even-numbered, saturated and unsaturated fatty acids (in the ratio 2:1) ranging from C16 to C18. Palmitic and oleic acids were the prominent fatty acids. Aspartic and glutamic acids, leucine, glycine and alanine were the major amino acids. Non-pigmented cells of F. pedrosoi were studied for comparison with the pigmented forms: they did not accumulate acid-insoluble precursors of melanin. PMID- 1856681 TI - Effect of iron deprivation on surface composition and virulence determinants of Candida albicans. AB - Six strains of Candida albicans were grown in defined medium which had been deferrated by ion-exchange chromatography and then supplemented with FeCl3 to give iron concentrations ranging from 0.026 microM to 0.8 microM. Growth in 0.026 microM-iron (measured as increase in biomass) was reduced by 26-59% as compared with that in excess (0.8 microM) iron. With five of the strains, adhesion to buccal epithelial cells was maximal after growth in 0.2-0.4 microM-iron, but strain GDH 2023 adhered best when grown in 0.026 microM-iron. Differences in yeast cell-wall composition were revealed by Zymolyase treatment of whole cells and by 125I-labelling of surface proteins. SDS-PAGE of iodinated proteins, followed by autoradiography, showed quantitative but no qualitative differences in protein profiles of iron-deficient and iron-replete organisms. The ability of all strains to form germ tubes in serum was near-maximal after growth in 0.2-0.4 microM-iron but was inhibited by up to 93% following growth in lower concentrations. These results indicate that expression of important virulence attributes by C. albicans is highly dependent on available iron and that expression in vivo may therefore be significantly different from that observed under conventional laboratory conditions. PMID- 1856680 TI - Efficient translation of synthetic and natural mRNAs in an mRNA-dependent cell free system from the dimorphic fungus Candida albicans. AB - An mRNA-dependent cell-free translation system has been developed from the human pathogenic fungus Candida albicans using either S30 or S100 lysates prepared from glass-bead-disrupted whole cells. Translation of the synthetic template poly(U) in this system is highly efficient at temperatures up to 37 degrees C and is ATP dependent. Studies using a range of elongation-specific inhibitors suggest that the mechanism of translational elongation in C. albicans is similar to that of another yeast, Saccharomyces cerevisiae. A micrococcal-nuclease-treated C. albicans S100 lysate was able to translate exogenously-supplied homologous mRNAs, and a range of heterologous natural mRNAs, using an initiation mechanism that is inhibited by the antibiotic edeine and the 5' cap analogue 7-methylguanosine 5' monophosphate (m7GMP). As with cell-free lysates prepared from S. cerevisiae, the C. albicans lysate is unable to initiate translation upon natural mRNAs at temperatures above 20 degrees C. PMID- 1856682 TI - Fatty acid oxidation and the beta-oxidation complex in Mycobacterium leprae and two axenically cultivable mycobacteria that are pathogens. AB - Intact, non-growing Mycobacterium leprae, M. avium and M. microti oxidized a wide range of 1-14C-labelled fatty acids (C8 to C24) to 14CO2. Laurate (C12) was oxidized most rapidly, and its oxidation by M. leprae was inhibited by the antileprosy agents Dapsone, clofazamine and rifampicin. Key enzymes of beta oxidation were detected in extracts from all three mycobacteria. All these activities (both in intact mycobacteria and the enzymes) were stimulated in M. avium grown in Dubos medium plus palmitate but activities in M. microti or M. avium grown either in Dubos medium with added liposomes or triolein, or in vivo were similar to those detected in the same strain grown in Dubos medium alone. M. avium could be grown in medium in which 95% of its fatty acyl elongase activity is acetyl-CoA dependent. In this medium growing M. avium organisms oxidized [1 14C]palmitate to 14CO2 but simultaneously elongated palmitate to C24 acids and even longer. Acetyl-CoA-dependent elongase activity is similar but clearly not identical to reversed beta-oxidation, but the exact point(s) of difference have not yet been identified. PMID- 1856683 TI - Changes in the activities of key enzymes of glycolysis during the cell cycle in yeast: a rectification. AB - Activities of glycolytic enzymes were determined in elutriation fractionated cultures of Saccharomyces cerevisiae grown on different carbon sources. Almost pure fractions of single cells at the G1 state of cell division were obtained for some of the growth conditions tested, whereas other stages were enriched in particular fractions. Specific activities of glucose-6-phosphate dehydrogenase and alcohol dehydrogenase were found to be constant during the cell cycle, as reported by van Doorn et al. (1988a), Journal of Bacteriology 170, 4808-4815, and (1988b), Journal of General Microbiology 134, 785-790. In contrast to the earlier reports, the activities of hexokinase, phosphofructokinase, pyruvate kinase and trehalase were also constant in different states of the cell cycle. For hexokinase and phosphofructokinase it was shown that the apparent specific activity in a cell-free extract strongly diminished when extracts contained less that 0.5-1 mg protein ml-1. In the experiments of van Doorn et al. (1988a) the protein content of the outer fractions was up to 20 times lower than that of the central fractions, suggesting an alternative explanation for the observed changes in enzyme activities during the cell cycle. Therefore, we want to rectify the observations presented by van Doorn et al. (1988a), and conclude that the activities of the glycolytic enzymes do not vary greatly during the cell cycle of S. cervisiae. PMID- 1856684 TI - Ammonium transport in Escherichia coli: localization and nucleotide sequence of the amtA gene. AB - Escherichia coli expresses a concentrative ammonium (methylammonium) transport system which is strongly repressed under conditions of nitrogen excess. We have previously reported the cloning of a structural gene (amtA) for this transporter by complementation. In this study, a 3.4 kb HindIII-BamHI fragment containing amtA was cloned into the pBluescript KS(+) vector, and unidirectional nested deletions from each end of this 3.4 kb fragment were generated by exonuclease III digestion. The deletions were analysed by complementation of the structural gene mutation produced by Tn10 insertion. This allowed amtA to be localized within a 1.4 kb region which spans the site of the mutation. By application of the Sanger dideoxy method, we sequenced the region containing amtA. The gene contains an open reading frame which encodes a protein with a predicted molecular mass of 27 kDa. The open reading frame is preceded by a putative Shine-Dalgarno sequence and followed by an inverted repeat which might function as a simple transcription terminator. Hydropathic analysis of the inferred amino acid sequence of the gene product predicts that amtA encodes a cytoplasmic component of the ammonium transport system. PMID- 1856685 TI - Cloning, sequencing, and mutational analysis of the Bradyrhizobium japonicum fumC like gene: evidence for the existence of two different fumarases. AB - The Bradyrhizobium japonicum fumarase gene (fumC-like) was cloned and sequenced, and a fumC deletion mutant was constructed. This mutant had a Nod+ Fix+ phenotype in symbiosis with the host plant, soybean, and growth in minimal medium with fumarate as sole carbon source was also not affected. The cloned B. japonicum fumC gene fully complemented an Escherichia coli Fum- mutant, strain JH400, for growth in minimal medium with fumarate. The predicted amino acid sequence of the FumC protein showed strong similarity to the E. coli FumC protein, Bacillus subtilis CitG protein, Saccharomyces cerevisiae Fum1 protein, and the mammalian fumarases. The B. japonicum FumC protein accounted for about 40% of the total fumarase activity in aerobically grown cells. The remaining 60% was ascribed to a temperature-labile fumarase. These data suggest that B. japonicum possesses two different fumarase isoenzymes, one of which is encoded by fumC. Besides E. coli, which has three fumarases, B. japonicum is thus the second bacterium for which there is genetic evidence for the existence of more than one fumarase. PMID- 1856686 TI - Phylogeny of capsid proteins of small icosahedral RNA plant viruses. AB - Statistically significant alignment was generated between the amino acid sequences of the (putative) shell (S) domains of the capsid proteins of small RNA plant viruses with icosahedral capsids in the tombusvirus, carmovirus, dianthovirus, sobemovirus and luteovirus groups. Inspection of the alignment showed good correspondence between the experimentally defined beta-strands and alpha-helices of the capsid proteins of tomato bushy stunt, southern bean mosaic and turnip crinkle viruses, allowing prediction of the secondary structure elements in proteins with unresolved tertiary structure. It is concluded that this set of viral capsid proteins forms a tight evolutionary cluster. Comparison of the alignment of the proteins of this family with the sequences of other capsid proteins of icosahedral RNA viruses revealed more distant similarities to the satellites of tobacco necrosis, panicum mosaic, tobacco mosaic and maize white line mosaic viruses, as well as to nepo- and comoviruses. The tentative phylogenetic tree derived from the capsid protein alignment separated into three main lineages: (I) carmo-, tombus- and dianthoviruses, (II) southern bean mosaic, tobacco necrosis and maize chlorotic mottle viruses, and (III) luteoviruses. Comparison of this tree topology with the tentative evolutionary schemes for the respective virus RNA-dependent RNA polymerases suggested that gene shuffling is the universal trend in the evolution of small RNA plant virus genomes. PMID- 1856687 TI - The complete nucleotide sequence of cucumber green mottle mosaic virus (SH strain) genomic RNA. AB - The complete nucleotide sequence of the genomic RNA of cucumber green mottle mosaic virus watermelon strain SH (CGMMV-SH) was determined using cloned cDNA. This sequence is 6421 nucleotides long containing at least four open reading frames, which correspond to 186K, 129K, 29K and 17.3K proteins. The 17.3K protein is the coat protein. Sequence analysis shows that CGMMV-SH is very closely related to another watermelon strain. CGMMV-W, although three amino acid substitutions in the 29K protein were found between these strains. The sequence was also compared to those of other tobamoviruses, tobacco mosaic virus (TMV) vulgare, TMV-L (a tomato strain) and tobacco mild green mosaic virus reported by other groups. It shows 55 to 56% identity with these viruses. The size and location of the open reading frames are very similar to those of TMV but the 129K and 186K proteins are composed of 1142 and 1646 amino acids, being larger than those of TMV by 27 and 31 amino acids, respectively. The deduced amino acid sequences of these proteins are highly homologous to those of TMV, especially in the readthrough downstream region of the 186K protein. PMID- 1856688 TI - Evidence that the 75K readthrough protein of beet necrotic yellow vein virus RNA 2 is essential for transmission by the fungus Polymyxa betae. AB - Two mutant strains of beet necrotic yellow vein virus (BNYVV) containing deletion mutants of RNA-2 were produced during serial passage in mechanically inoculated Tetragonia expansa leaves. The mutant strains were referred to as S-0a (RNA-1 + 2a) and G-0b (RNA-1 + 2b). RNA-2a and RNA-2b were about 4.3 kb and 4.2 kb in length, respectively, whereas normal sized RNA-2 was about 4.8 kb in length. In vitro translation and immunoblot analysis showed that RNA-2, RNA-2a and RNA-2b all directed synthesis of the coat protein (Mr 22K). However, whereas wild-type RNA-2 also directed the synthesis of a coat protein readthrough protein with an Mr of 83K (predicted Mr 75K), RNA-2a and RNA-2b directed the production of readthrough proteins with MrS of 67K and 58K, respectively. This suggests that the deleted regions of RNA-2a and RNA-2b occur within the second open reading frame, which encodes a polypeptide of Mr 54K, which is translated by readthrough of the coat protein cistron. After the addition of wild-type RNA-3 and RNA-4 to all the strains, the mutant strains could not be transmitted by Polymyxa betae zoospores produced from either zoosporangia or resting spores, whereas the wild type strains were readily transmitted. These results indicate that the 75K readthrough protein encoded by RNA-2 is essential for the transmission of BNYVV by P. betae. PMID- 1856689 TI - Nucleotide sequence of tomato ringspot virus RNA-2. AB - The sequence of tomato ringspot virus (TomRSV) RNA-2 has been determined. It is 7273 nucleotides in length excluding the 3' poly(A) tail and contains a single long open reading frame (ORF) of 5646 nucleotides in the positive sense beginning at position 78 and terminating at position 5723. A second in-frame AUG at position 441 is in a more favourable context for initiation of translation and may act as a site for initiation of translation. The TomRSV RNA-2 3' noncoding region is 1550 nucleotides in length. The coat protein is located in the C terminal region of the large polypeptide and shows significant but limited amino acid sequence similarity to the putative coat proteins of the nepoviruses tomato black ring (TBRV), Hungarian grapevine chrome mosaic (GCMV) and grapevine fanleaf (GFLV). Comparisons of the coding and non-coding regions of TomRSV RNA-2 and the RNA components of TBRV, GCMV, GFLV and the comovirus cowpea mosaic virus revealed significant similarity for over 300 amino acids between the coding region immediately to the N-terminal side of the putative coat proteins of TomRSV and GFLV; very little similarity could be detected among the non-coding regions of TomRSV and any of these viruses. PMID- 1856690 TI - The nucleotide sequence of the infectious cloned DNA components of potato yellow mosaic virus. AB - The complete nucleotide sequence of a Venezuelan isolate of potato yellow mosaic virus (PYMV) has been determined, showing it to be typical of subgroup I geminiviruses in that it is whitefly-transmitted, has a circular, bipartite ssDNA genome and possesses bidirectionally orientated open reading frames (ORFs). The two genomic components have little sequence similarity apart from a common region of 268 nucleotides (nt) which is almost identical. Analysis of ORFs revealed six potential coding regions encoding proteins of Mr greater than 10K, four in PYMV A (2593 nt) and two in PYMV B (2547 nt), which are preceded by regulatory transcription elements and have polyadenylation signals present at the ends. Amino acid sequence alignments of PYMV DNA ORF-encoded proteins with those encoded by other previously sequenced geminivirus ORFs show that PYMV is closely related to those geminiviruses isolated from the New World, especially in the putative coat protein gene regions. PMID- 1856691 TI - The complete nucleotide sequence of tobacco necrosis virus strain D. AB - The complete sequence of the RNA genome of tobacco necrosis virus strain D (TNV D) consisting of 3759 nucleotides has been determined. The positive strand contains five open reading frames (ORFs). The 5'-proximal ORF encodes a 22K protein terminating with an amber codon which may be read through to produce a 82K protein (p82). Two small centrally located ORFs each encode two out-of-frame 7K proteins (p7a and p7b). The 3'-proximal ORF encodes the 29K coat protein (CP), the N terminus of which has been sequenced directly. The genomic organization of TNV-D is very similar to that of TNV-A but differs in the placement of the p7a ORF, which does not overlap the p82 ORF in TNV-D, and in the absence of an ORF downstream of the CP gene in TNV-D. The p82 ORF shows extensive sequence similarity with the putative polymerases of the carmovirus group. This ORF is also as closely related to the corresponding ORF of TNV-A as it is to the corresponding ORF of the tombusvirus cucumber necrosis virus. The amino acid sequence of the TNV-D CP gene is similar to both the TNV-A and southern bean mosaic virus CP genes. Of the two p7 ORFs, p7a exhibits amino acid sequence similarity with corresponding proteins from TNV-A, melon necrotic spot virus, carnation mottle virus, turnip crinkle virus and maize chlorotic mottle virus, whereas the p7b ORF appears to be unique to TNV-A and TNV-D. Only the 3'-terminal three nucleotides of TNV-D genomic RNA are identical to the 3'-terminal nucleotides of the TNV satellite virus. PMID- 1856692 TI - Expression of potyvirus coat protein in Escherichia coli and yeast and its assembly into virus-like particles. AB - When the full-length coat protein (CP) of the potyvirus, Johnsongrass mosaic virus (JGMV), was expressed in Escherichia coli or yeast, it assembled to form potyvirus-like particles. The particles were heterogeneous in length with a stacked-ring appearance and resembled JGMV particles in their flexuous morphology and width. This cell-free assembly system should permit analysis of the mechanisms of particle assembly and genome encapsidation. Two mutant forms of CP produced by site-directed mutagenesis failed to assemble into virus-like particles. PMID- 1856693 TI - Proteolytic processing of Semliki Forest virus-specific non-structural polyprotein. AB - The processing and stability of the non-structural (ns) proteins of Semliki Forest virus were studied in vivo. Virus-specific proteins from infected cells were identified by immunoprecipitation with monospecific antisera. The complete ns precursor, P1234, translated within 7 to 9 min of the start of translation, was processed before the completion of translation into P123 and nsP4. Pulse chase experiments showed that the mature ns proteins were relatively stable for at least 2 h. Interestingly, the decrease in the amount of the P34 precursor during chase is accompanied by an increase only in the amount of nsP3, which could explain the observed lower amount of nsP4 in infected cells. In cells infected with SFV RNA- mutants ts4 and ts6 maintained at the restrictive temperature, nsP4 but no nsP1, nsP2 or nsP3 accumulated in addition to the ns precursor proteins P1234, P123, P12 and P34. Translation in vitro of mRNAs from a cDNA clone, encoding P1234 with a deletion in the carboxy-terminal proteinase domain of nsP2, did not yield nsP1, nsP2 or nsP3 but only nsP4, indicating that cleavage at the nsP3/4 sites is independent. Evidently, nsP4 is produced by a nascent cleavage of the growing P1234, catalysed by its own proteinase activity; the proteolytic cleavages at the nsP1/2 and nsP2/3 sites are catalysed by the proteinase moiety of nsP2. PMID- 1856694 TI - Characterization of defective interfering RNAs of Berne virus. AB - Defective interfering (DI) RNAs of Berne virus (BEV) were generated by serial undiluted passaging of the virus in embryonic mule skin cells. Two DI RNAs of 1.0 and 1.4 kb (designated DI1000 and DI1400) were characterized in more detail. Isokinetic sucrose gradient analysis showed that these DI RNAs are specifically packaged into particles with smaller S values than standard virions. Both DI RNAs were cloned and sequenced. Three genomic cDNA clones were identified using probes complementary to the 5' end of a DI RNA, which are thought to be derived from the 5'-terminal region of the BEV genome. A non-translated region of about 700 nt and the 5' end of the putative BEV replicase gene were identified in the consensus nucleotide sequence. Both DI RNAs were shown to contain sequences from the 5' and 3' ends of the BEV genome. A conserved sequence motif, which has been postulated to be involved in sub-genomic RNA transcription, was also identified just downstream of the extreme 5' ends of DI1000 and DI1400. PMID- 1856695 TI - Sequence analysis of the turkey enteric coronavirus nucleocapsid and membrane protein genes: a close genomic relationship with bovine coronavirus. AB - The 3' end of the turkey coronavirus (TCV) genome and the gene encoding the nucleocapsid protein (N) were cloned and sequenced. The gene encoding the membrane protein (M) was obtained by cloning a polymerase chain reaction (PCR) amplified fragment obtained using bovine coronavirus (BCV)-specific primers. Furthermore, five TCV DNA fragments, obtained by PCR on RNA from clinical specimens and corresponding to either the N terminus of the M protein or the complete M protein were also cloned and sequenced. The sequence revealed a 3' non coding region of 291 bases, an open reading frame (ORF) encoding the N protein with a predicted size of 448 amino acids, or an Mr of 49K, and an ORF encoding the M protein with a predicted size of 230 amino acids and an Mr of 26K. A third ORF, encoding a hypothetical protein of 207 amino acids with an Mr of 23K was found within the N gene sequence. The amino acid sequences of both the N and M proteins were more than 99% similar to those published for BCV. Extensive similarity was also observed between the amino acid sequences of the TCV N protein and those of murine hepatitis virus (MHV) (70%) and human respiratory coronavirus strain OC43 (HCV-OC43) (98%) and between the amino acid sequences of the predicted M proteins of TCV and MHV (86%). Such striking identity suggests that BCV, TCV and HCV-OC43 must have diverged from each other only recently. A potential N-glycosylation site was found at the N terminus of the TCV M protein and is situated at the same location in BCV, MHV and transmissible gastroenteritis virus. PMID- 1856696 TI - Localization of the influenza virus nucleoprotein: cell-associated and extracellular non-virion forms. AB - Both the supernatant of influenza virus-infected chick embryo cells and allantoic fluid containing influenza virus were shown to contain non-virion nucleoprotein (NP), which reacted readily with anti-NP monoclonal antibodies. Adsorption onto erythrocytes and centrifugation at 70,000 g for 2 h resulted in the removal of about 20% of the extracellular NP, whereas centrifugation at 100,000 g for 4 h eliminated about 50%, and practically all [3H]uridine-labelled virions. These results suggest that of the extracellular NP about 30% exists in the form of ribonucleoprotein, about 20% is precipitated with virions and about 50% occurs as free molecules. Comparative analysis of the kinetics of the accumulation of NP in the supernatant of infected cells, on the cell surface and inside the cells in relation to virus production, showed that there is a significant correlation between them. PMID- 1856697 TI - The 36K polypeptide synthesized in Newcastle disease virus-infected cells possesses properties predicted for the hypothesized 'V' protein. AB - Newcastle disease virus (NDV) virions possess two proteins which react strongly with monoclonal antibody 688 following separation by high resolution two dimensional (isoelectric focusing/SDS) PAGE and detection by Western blotting. One is the phosphorylated nucleocapsid-associated 53K [P (NAP)] protein, the other comigrates with the 36K protein detected by radiolabelling NDV-infected chick embryo fibroblasts. [35S]Cysteine/[3H]leucine dual-labelling experiments show that the 36K protein is very rich in cysteine compared to the P (NAP) protein. In the Beaudette C strain it comigrates on one-dimensional SDS polyacrylamide gels with the matrix protein (M); however, it is resolved from the slower migrating M protein from the Ulster strain of NDV. The size, strain specific isoelectric point, high cysteine content and antigenic relatedness to the P (NAP) protein suggest that the 36K protein is the 'V' protein of NDV, the counterpart of which is found in other Paramyxoviridae. PMID- 1856698 TI - Nucleotide sequence analysis of a matrix and small hydrophobic protein dicistronic mRNA of bovine respiratory syncytial virus demonstrates extensive sequence divergence of the small hydrophobic protein from that of human respiratory syncytial virus. AB - The nucleotide and deduced amino acid sequences of the matrix (M) and small hydrophobic (SH) proteins of bovine respiratory syncytial virus (BRSV) have been determined from a dicistronic mRNA. Comparison of these sequences with the corresponding published sequences of human respiratory syncytial virus (HRSV) revealed extensive overall homology at both the nucleotide and amino acid levels in the M protein, but low overall homology at both the nucleotide and amino acid levels in the SH protein. There was only 16 to 22% identity between the BRSV SH protein and the HRSV SH proteins at the C terminus. There were also an additional eight amino acids at the C terminus of BRSV. Despite the low level of identity, there were similarities in the predicted hydropathy profiles of BRSV and HRSV SH proteins. The transcription start and stop signals, which are conserved among HRSV mRNAs, were also identified in the M-SH dicistronic mRNA of BRSV. In addition, the intergenic sequence for the M-SH gene junction of BRSV was determined. PMID- 1856699 TI - Binding of the BL/VL3 murine T cell lymphoma to radiation leukaemia virus is specific for viral env determinants. AB - Molecularly cloned radiation leukaemia viruses (RadLVs) isolated from the BL/VL3 radiation-induced thymoma have been used in assays to compare the binding specificity of the BL/VL3 cell line for different retroviruses. BL/VL3 cells bound well to two of three thymotropic, leukaemogenic viruses produced by this cell line. BL/VL3 did not bind to a cloned fibrotropic, non-leukaemogenic RadLV. BL/VL3 appears to have receptor specificity for only some of the leukaemogenic RadLVs, and this appears to be related to differences in the viral env sequence. PMID- 1856700 TI - Characterization of the genome of cacao swollen shoot virus. AB - Cacao swollen shoot disease has been known to be caused by a small non-enveloped bacilliform virus for more than 25 years. Purification using a combination of celite filtration, polyethylene glycol concentration and sucrose density gradient centrifugation has yielded concentrated preparations of purified cacao swollen shoot virus (CSSV). Results of nuclease sensitivity tests indicated that the CSSV genome consists of dsDNA which has two single-stranded regions. The approximate size of CSSV DNA calculated from restriction enzyme digests is 7.4 kbp. It is very likely that CSSV is a member of the commelina yellow mottle virus group. PMID- 1856702 TI - Temperature-sensitive replication of cucumber mosaic virus in muskmelon (Cucumis melo cv. Iroquois), maps to RNA 1 of a slow strain. AB - Several strains of cucumber mosaic virus have been categorized as either 'fast' or 'slow', based on the time of appearance of symptoms after inoculation onto zucchini squash (Curbita pepo cv. Black Beauty). These strains were examined for their ability to replicate in muskmelon (Cucumis melo cv. Iroquois) at elevated temperatures. All of the fast strains were able to replicate at 37 degrees C in muskmelon, whereas all of the slow strains were unable to replicate to detectable levels at 37 degrees C, but replicated efficiently at 27 degrees C. Using previously constructed pseudorecombinants between a fast and a slow strain, Fny- and Sny-CMV, temperature sensitivity was mapped to RNA 1 of the Sny-CMV strain. PMID- 1856701 TI - Nucleotide sequence of the 3'-terminal region of the RNA of the El Amar strain of plum pox potyvirus. AB - The nucleotide sequence of the 3'-terminal 4773 nucleotides of the RNA of a widely divergent, aphid-transmissible strain of plum pox potyvirus isolated from Egypt (PPV-El Amar) was determined. The sequenced region covers the carboxy terminus of the cylindrical inclusion (CI) gene, and the putative 6K protein, the NIa protease, the NIb RNA polymerase and the coat protein genes, linked together as one large open reading frame (ORF) in a fashion similar to the canonical genomic organization of other potyviruses. The large ORF encoding the polyprotein is followed by a 217 nucleotide non-coding region and a poly(A) tail. However, whereas the three PPV strains previously sequenced show levels of identity in excess of 98%, PPV-El Amar shows levels of heterogeneity of 20% in the nucleotide sequence and 10% in the amino acid sequence, when compared with these previously sequenced strains. The N-terminal region of the capsid protein, postulated to be involved in the aphid transmission mechanism of the virus, was found to be the region which differed most between PPV-El Amar and the other strains. PMID- 1856703 TI - A model for the generation of tobacco rattle virus (TRV) anomalous isolates: pea early browning virus RNA-2 acquires TRV sequences from both RNA-1 and RNA-2. AB - Comparison of the 5'-terminal sequences of several tobraviruses suggests that the RNA-2 molecule of the tobacco rattle virus (TRV) anomalous isolate TCM arose from pea early browning virus (PEBV) RNA-2 by acquisition of 3' and 5' sequences from TRV RNA-1 and RNA-2 molecules, respectively. We have identified a region of homology in the RNA-2 molecules of PEBV, TRV and pepper ringspot virus which could have facilitated this recombination. PMID- 1856704 TI - Recognition of the N-terminal, C-terminal, and interior portions of HBx by sera from patients with hepatitis B. AB - We have cloned and expressed in Escherichia coli three different parts of the HBx open reading frame, the N- and C-termini and the interior or central portion, using two vector systems. The sera of 43 hepatitis B virus patients representing three clinical categories--asymptomatic carriers, chronic active hepatitis, and hepatitis B patients with cirrhosis--known to be anti-HBx positive, were tested for reactivity against these constructs by Western blotting. The great majority of sera, regardless of the clinical categories, clearly recognise all three parts of HBx, strongly suggesting that the normal mechanism of biosynthesis of the HBx gene product is a straight-forward translation of the open reading frame starting from the first ATG. However, asymptomatic carriers show a marked, often almost exclusive, preference for recognition of the central portion of HBx, while patients with chronic hepatitis and patients with cirrhosis generally recognise all three parts of HBx to a similar extent. PMID- 1856705 TI - Characterization of HBV2-like infections in Spain. AB - Hepatitis B viral serum markers suggestive of infection by hepatitis B virus type 2 were found in 354 patients tested in the laboratory during a 2.5 year period of study. Confirmation of the HBsAg reactivity by neutralization and subtyping analysis and determination of serum HBV-DNA by molecular hybridization were carried out on selected samples from these patients. Clinical and epidemiological data were obtained from 234 patients and serological follow-up was done in 70 cases. The results obtained from the confirmatory tests and DNA assays indicated that HBsAg reactivities were specific, being frequently associated to low levels of HBV-DNA. The incidence rates obtained for HBV2 serological patterns among patients at different level of risk for HBV infection, as well as the finding of a high rate of coinfection with hepatitis A virus among those showing acute hepatitis, suggested that the HBV2 agent could be transmitted by the oral route. An hypothesis considering the so called HBV2 infections as resulting from infections by an HBV variant strain which has an improved ability for non-sexual, non-parenteral transmission is suggested. Specific recommendations for detection and confirmation of such cases in blood banks are also outlined. PMID- 1856706 TI - Significance of IgM anti-hepatitis D virus (HDV) in chronic HDV infection. AB - Intrahepatic hepatitis D virus (HDV) antigen (HDAg) and serum HDV RNA are excellent markers of active HDV replication but the relation of IgM anti-HDV to HDV replication and histological activity is less certain. To further elucidate the significance of serum IgM anti-HDV, 90 paired sera and liver biopsies from 64 patients seropositive for total antibody to HDV were analysed for IgM anti-HDV, intrahepatic HDAg expression, and histological inflammatory activity. IgM anti HDV was strongly associated with intrahepatic HDAg expression with a sensitivity of 94.1% but the assay lacked specificity since 14 out of 22 cases negative for intrahepatic HDAg were also positive for IgM anti-HDV. In 20 patients in whom follow-up biopsies and paired sera were available, two patients lost intrahepatic HDAg but paired serum remained IgM anti-HDV positive. Although the presence of serum IgM anti-HDV correlated significantly with a higher histological inflammatory activity (P = 0.001), there was a considerable overlap with the group seronegative for IgM anti-HDV, again indicating a poor specificity. This lack of specificity of IgM anti-HDV for both HDV replication and histological activity indicates that this assay provides no additional information over and above assay for total antibody to HDV. PMID- 1856707 TI - A cognitive morphology of psychopathology. AB - In contrast to contemporary approaches to psychopathology that establish diagnostic taxonomies derived primarily from differences in manifest symptoms, this paper, based on an integration of cognitive and psychoanalytic developmental theory, proposes a structural cognitive morphology for understanding and assessing differences among various forms of psychopathology, from schizophrenia to the neuroses. A theoretical model based on the development of cognitive schema, consistent with clinical and research data, considers schizophrenia and paranoid schizophrenia as involving fundamental disturbances in boundary articulation and recognition constancy, and considers borderline personality disorders as involving disturbances in evocative constancy. Also, a lack of integration of object and self-schema, expressed in either a distorted and exaggerated preoccupation with interpersonal relatedness or self-definition, defines two primary personality configurations that have implications for understanding the neuroses and subtypes of depression, as well as differential response to various types of psychotherapeutic intervention. PMID- 1856708 TI - Cognitive-behavioral therapy for panic: an open study. AB - This paper reports results of an open prospective study of 26 patients who met DSM-III criteria for panic disorder or agoraphobia with panic attacks. Cognitive behavioral treatment alone produced clinically and statistically significant improvement in panic symptoms, including both full-blown and limited symptom episodes. In addition, the treatment produced improvement in associated symptoms of phobic avoidance and generalized anxiety. This work provides further preliminary indication of the usefulness of cognitive-behavioral strategies as an alternative to medication in symptom-oriented treatments. PMID- 1856709 TI - Cognitive-behavior therapy for panic disorder delivered by psychopharmacologically oriented clinicians. AB - A cognitive-behavioral treatment program for panic disorder was delivered by staff members of a psychiatric center that traditionally utilizes pharmacological methods. Psychiatrists, a nurse practitioner, and psychologists not previously exposed to behavioral techniques were trained by a behavioral psychologist to utilize a treatment program consisting of breathing control, cognitive restructuring, and exposure to panic-eliciting somatic cues. Of the 24 patients treated as part of this training in panic control therapy, 14 were panic-free after treatment and three additional patients showed moderate improvement and decreased frequency of panic. A case example is presented to demonstrate the application of behavioral techniques to individual patients. Discussion is focused on issues surrounding training in behavioral methods and problems in exporting behavioral technology to centers that emphasize psychopharmacological approaches to treatment. PMID- 1856710 TI - Early dropouts from psychotherapy. AB - Ninety-six patients requesting psychotherapy were studied prospectively at the time of screening interview by four senior psychiatrists using a variation on Luborsky's Helping Alliance questionnaire and the Osgood Semantic Differential. Significant differences were found at the time of screening between early dropouts and continuers, among screeners' rate of early dropouts, and among patients' perceptions of screeners. The screener with a high early dropout rate was seen as being more passive and less potent, and offering less new understanding than other screeners. Patients who dropped out early experienced a less strong helping alliance, felt they gained less new understanding, liked the clinician less well, felt less well liked and less respected, and saw the interviewer as more passive and psychotherapy as less potent than did continuers. PMID- 1856711 TI - The pet as an anxiolytic intervention. AB - The effect of a pet on psychological consequences of stress (i.e., state and trait anxiety levels) of college students was examined under three test conditions (i.e., reading aloud, reading quietly, and interacting with a friendly but unknown dog). A repeated-measures analysis of variance with three covariates was used to examine the effect of the treatment on each dependent variable (state and trait anxiety). Reading aloud differed from baseline measure under all treatment conditions (p less than .001). Reading quietly and interacting with the dog were slightly below baseline for variables, with more effect seen by reading quietly than by interacting with the dog. Examination of interactions among variables showed no significant differences. Effects upon state anxiety were significant, while trait anxiety levels remained fairly constant throughout the treatments. Baseline differences in trait anxiety scores indicate a potentially greater benefit for pet owners than nonowners. Selected social network and relationship data related to the role of the pet during anxiety-producing times were also analyzed. While interaction with the pet produced a decrease in anxiety level, pet owners did not report the use of their own pet as a social support (i.e., as confidant) significantly more than did previous owners. Results indicated that interacting with a pet for some individuals does affect both physiological and psychological responses by lowering response levels. However, a parallel effect was also seen by reading quietly. Given the effect of pet interaction upon selected social support indicators of health in well college students, these data suggest the importance of examining this treatment with an "at-risk" group in which it is possible to control for ownership characteristics. PMID- 1856712 TI - Alexithymic characteristics and metabolic control in diabetic and healthy adults. AB - Diabetes has long been identified as a disease with possible psychological components. Alexithymia--an inability to express emotions verbally, operational thinking, and a lack of fantasy life--is found in a high proportion of psychosomatic patients. We therefore tested the hypothesis that diabetics would be more alexithymic than controls. In addition, the lack of awareness of affect was hypothesized to have negative consequences for the management of diabetes, as reflected in metabolic glucose control (HbA1). The number of emotion words produced in six imaginative (Thematic Apperception Test) stories was used as the measure of alexithymia, with few words reflecting alexithymic characteristics. Diabetics were found to be significantly more alexithymic than controls. Further, fewer emotion words (alexithymia) was associated with poorer metabolic control. These data suggest that alexithymic characteristics may interfere with a diabetic's ability to manage their illness, and support previous research showing that the suppression of emotions can lead to a difficulty in regulating glucose levels. PMID- 1856713 TI - Signal detection analysis of short-term recall in schizophrenia. AB - Unlike many traditional performance measures, signal detection indices of sensitivity are free of response biases. Signal detection and traditional indices of performance were obtained from a short-term recall task during distractor and neutral conditions for schizophrenic patients and normal subjects. Items in each condition had been matched previously for difficulty and consistency to determine whether diminished recall during distraction represented a true differential deficit. Results showed similar patterns for both types of indices: normal subjects performed better than patients across both conditions, patients recalled less after presentation of a distractor than during a neutral condition, and normal subjects showed no performance decrement between the two conditions. These findings demonstrated that the differential deficit was due to changes in schizophrenic patients' sensitivity to stimulus items, not response biases. PMID- 1856714 TI - Discontinuation of lithium treatment in remitted bipolar patients: relationship between clinical outcome and changes in sleep-wake cycles. AB - In this preliminary report, we describe four patients in whom long-term lithium therapy was discontinued, combined with actigraphic monitoring to assess changes in motor activity and the sleep-wake cycle. Two patients experienced rapid relapse of manic symptomatology, while two remained stable throughout a 1-year follow-up. Actigraphic monitoring revealed disintegration of the sleep-wake cycle and increased motor activity in the relapsed patients only. It is suggested that actigraphic recordings can be used to monitor lithium discontinuation. PMID- 1856715 TI - An abbreviated questionnaire for quantifying treatment requests from Dutch outpatients. PMID- 1856716 TI - Valproate for rapid-cycling unipolar affective disorder. PMID- 1856717 TI - Self-mutilation by a man with posttraumatic stress disorder. PMID- 1856718 TI - Analysis of executive functioning in schizophrenics using the Wisconsin Card Sorting Test. PMID- 1856719 TI - Protein interactions with surface-immobilized metal ions: structure-dependent variations in affinity and binding capacity with temperature and urea concentration. AB - We have used equilibrium binding analyses to evaluate the influence of temperature and urea on the affinity of hen egg white lysozyme and bovine pancreatic ribonuclease A for surface-immobilized Cu(II) ions. Linear Scatchard plots suggested that these model proteins were interacting with immobilized metal ions via a single class of intermediate-affinity (Kd = 10-40 microM) binding sites. Alterations in temperature had little or no effect on the immobilized Cu(II) binding capacity of either protein. Temperature effects on the interaction affinity, however, were protein-dependent and varied considerably. The affinity of lysozyme for immobilized Cu(II) ions was significantly decreased with increased temperature (0 degree C-37 degrees C), yet the affinity of ribonuclease did not vary measurably over the same temperature range. The van 't Hoff plot (1n K vs 1/T) for lysozyme suggests a straight line relationship (single mechanism) with a delta H of approximately -5.5 kcal/mol. Urea effects also varied in a protein-dependent manner. A 10-fold reduction in the affinity of lysozyme for the immobilized Cu(II) was observed with the urea concentrations up to 3 M; yet urea had no effect on the affinity of ribonuclease for the immobilized metal ions. Although the interaction capacity of lysozyme with the immobilized Cu(II) ions was decreased by 50% in 3 M urea, ribonuclease interaction capacity was not diminished in urea. Thus, temperature- and urea-dependent alterations in protein metal ion interactions were observed for lysozyme but not ribonuclease A. The complete, yet reversible, inhibition of lysozyme- and ribonuclease-metal ion interactions by carboxyethylation with low concentrations of diethylpyrocarbonate provided direct evidence of histidyl involvement. The differential response of these proteins to the effects of temperature and urea was, therefore, interpreted based on calculated solvent-accessibilities and surface distributions of His residues, individual His residue pKa values, and specific features of the protein surface structure in the immediate environment of the surface-exposed histidyl residues. Possible interaction mechanisms involved in protein recognition of macromolecular surface-immobilized metal ions are presented. PMID- 1856720 TI - A circular dichroic study of Cu(II) binding to bovine alpha-lactalbumin. AB - The visible and ultraviolet circular dichroic spectra resulting from the interaction of bovine alpha-lactalbumin with successive Cu(II) ions have been recorded under a variety of conditions. Analysis of the observed change-transfer and d-d band transitions can be made in terms of two kinds of binding sites: at a histidyl group and at the N-terminal amino group, respectively. At basic pH the amide nitrogens of the peptide backbone progressively take part in the coordination. The occupation of the high affinity calcium binding site by Ca(II) and Mn(II) does not influence the Cu(II) binding process, suggesting that there is no direct interaction between this site and the Cu(II) binding sites. PMID- 1856721 TI - Thermodynamic data on the binding of six M2(+)-ions to bovine, goat, and human alpha-lactalbumin. AB - By batch microcalorimetry we titrated the apo-forms of bovine, goat, and human alpha-lactalbumin with Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, and Cd2+ ions at pH 7.5 and 25 degrees C. The titration curves enabled us to calculate the apparent enthalpy changes and binding constants and thus, also the free energy and the entropy changes of the binding. CD-spectra showed that all cations induce the same conformational change to the native form of the protein. The calorimetric and spectroscopic results, as well as sequence comparisons confirm the hypothesis that all these ions occupy the very same site on the molecule. The thermodynamic parameters, plotted vs the ionic radii, run parallel for the three proteins, which illustrates the earlier proposed "rigid site" model. PMID- 1856722 TI - Organomercury(II) complexes of 6-thioguanine: synthesis, characterization, and biological studies. AB - Organomercury(II) complexes involving 6-thioguanine, of the type p-XC6H4HgL (Fig. 1) [LH = 6-thioguanine; X = Me, MeO, NO2], have been synthesized and characterized. Conductance measurements indicate that the complexes are nonelectrolytes. From IR and UV studies, it is concluded that 6-thioguanine acts as a bidentate ligand, coordinating through the 6-thione group and deprotonation of N-7. 1H and 13C NMR support the stoichiometry of the complexes. From thermal studies (TG and DSC) various kinetic and thermodynamic parameters for thermal degradation have been enumerated. In addition, the fragmentation pattern of the complexes have been analyzed on the basis of mass spectra. The p-MeC6H4HgL and p MeOC6H4HgL complexes display significant activity against L1210 leukemia cells. PMID- 1856723 TI - Acetazolamide-M(II) [M(II) = Co(II),Ni(II),Cu(II)] complexes with ethylamine, diethylamine, triethylamine, and potassium hidroxide. AB - Complexes of Co(II), Ni(II), and Cu(II) with dideprotonated Acm are synthesized and characterized. Acm acts as bidentate ligand through the N-sulfonamido atom and the N-thiadiazole atom except for K6CoAcm4.6H2O in which Acm behaves as monodentate through the N-sulfonamido atom. PMID- 1856724 TI - Binding of mercury(II) to protein thiol groups: a study of proteinase K and carboxypeptidase Y. AB - Chemically modified enzymes have been prepared by incorporating an -Hg-L group into proteinase K and carboxypeptidase Y at the thiol groups of Cys-73 and Cys 341, respectively (L = CN- or I-). The -S-Hg-13CN group has been applied as a spectroscopic label for carbon-13 NMR spectroscopy. PMID- 1856725 TI - The need for adequate control groups in nutrition studies. PMID- 1856726 TI - Increased interleukin-1 production by peripheral blood mononuclear cells in patients with multiple sclerosis. AB - The production of interleukin-1 (IL-1) by peripheral blood mononuclear cells (MNC) was assessed in patients with relapsing multiple sclerosis (MS) in both the active and inactive phase, in chronic progressive MS patients, in other neurological diseases, and in healthy subjects. Production was determined by measuring the IL-1 concentration in cultures with MNC supernatants using enzyme linked immunosorbent assay (ELISA). IL-1 in sera of MS patients and healthy subjects also was investigated. MNC IL-1 alpha production was significantly higher in MS patients (180.2 +/- 177.5 pg/ml) than in healthy subjects (66.2 +/- 66.0 pg/ml) (P less than 0.05). Relapsing MS patients in the active phase had significantly higher MNC IL-1 alpha concentrations (360.1 +/- 130.0 pg/ml) than normal subjects (P less than 0.001), but MNC IL-1 alpha production in patients with relapsing MS in the inactive phase (65.3 +/- 52.8 pg/ml) or chronic progressive MS (80.9 +/- 71.9 pg/ml) was not increased significantly. MNC IL-1 beta production in MS patients was not elevated significantly. IL-1 alpha and -1 beta were not detected in sera of MS patients. The correlation between increased IL-1 alpha production and the clinical course of MS suggests that activated MNC may play a role in the pathogenesis of MS. PMID- 1856727 TI - Hyaluronidase as an adjuvant in the management of tuberculous spinal arachnoiditis. AB - Spinal arachnoiditis, a complication of tuberculous meningitis, is not uncommon; it may develop despite specific chemotherapy and steroids, and existing avenues of treatment for it are unsatisfactory. The enzyme hyaluronidase, by virtue of its action of hydrolysing the glucosaminidic bonds of hyaluronic acid and other mucopolysaccharides of the ground substance, offers a promising mode of treatment. Sixty-six patients with spinal arachnoiditis secondary to tuberculous meningitis were seen over an 8-year period. All these patients received antituberculous drugs and steroids; 39 of them (group A), who, in addition, were given intrathecal hyaluronidase, fared better than the remaining 27 (group B), who did not receive this enzyme. This study was non-randomised. The disability and functional deficit score showed a significant decrease from 7.6 to 3.7 in the enzyme-treated group in contrast to a mild change from 8.1 to 6.9 in the untreated group. Further, in group A the mortality was 5.2% whereas in group B it was 25.9%. There was a marked 5-fold decrease in mean CSF protein in group A while in group B there was no significant change. There were no serious side effects due to repeated administration of intrathecal hyaluronidase. Thus this study provides convincing evidence of the therapeutic role of hyaluronidase in the management of tuberculous spinal arachnoiditis and replicates our earlier observation of the safety of hyaluronidase given intrathecally. PMID- 1856728 TI - Pattern and ethnic variations in stroke in Saudi Arabia. AB - We report our observations in 427 stroke patients (305 Saudis, 122 non-Saudis with an age range of 14 months to 85 years) seen in a tertiary hospital in the eastern province of Saudi Arabia over an 8-year period. Of these patients, 115 (27%) were between 18 and 45 years old, and constituted the "young stroke patients" for this study. The hospital frequency for the young was 5/10,000 inpatients. In general, there was a male preponderance, with a male:female ratio of 2.2:1 and 7:1 for Saudis and non-Saudis, respectively. Ischemic stroke (55%) was more frequent than hemorrhagic stroke (25%), and the stroke was unspecified in 20%. The main etiologic factors were hypertension, diabetes mellitus and cardiac disorders. In the young population, the frequencies of hemorrhagic and ischemic strokes were similar. In this group, the main causes of intracerebral hemorrhage were aneurysms and arteriovenous malformations, while arteriosclerosis and embolism of cardiac origin were responsible for the ischemic strokes. In Saudis, the stroke types were 59% ischemic, and 17% hemorrhagic, as against 45 and 48% in non-Saudis, respectively. Most ischemic strokes were found in Saudis (78%). Intracerebral hemorrhage accounted for 63% of all hemorrhagic strokes, and was more frequent in Saudis but subarachnoid hemorrhage was three times more common in non-Saudis. In the young stroke patients, interethnic comparison showed that individuals from the Far East were nine times more likely to have hemorrhagic than ischemic stroke compared to the others (odd's ratio = 8.7), and the etiology of ischemic stroke remained undetermined in 67% of those from the Indian subcontinent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856729 TI - Sensitivity of eye movement registration and visual evoked potentials in evaluation of therapy in patients with multiple sclerosis. AB - A major problem in the evaluation of multiple sclerosis (MS) treatment protocols is the lack of an objective and reliable marker of disease activity. In 24 MS patients who were treated with high doses of intravenous methylprednisolone because of an acute relapse or progressive disease the clinical improvement (as measured by the Kurtzke expanded disability status scale) was compared with two paraclinical parameters, i.e. visual evoked potentials (VEP) and the registration of saccadic and smooth pursuit eye movements. After treatment a significant clinical improvement was found in 50% of the patients. The registration of eye movements revealed a significant improvement in 83% of the patients, the VEP in 21%. It is demonstrated that especially the registration of eye movements can have an important application as an objective and sensitive method in the assessment of neurological functions during MS treatment protocols. PMID- 1856730 TI - Cerebral hypoperfusion correlates with mild and parenchymal loss with severe multi-infarct dementia. AB - Relative contributions of two potential pathogenetic factors for cognitive impairments among patients with multi-infarct dementia (MID) are reported. Cognitive test scores were correlated with measures of cerebral hypoperfusion and loss of brain parenchyma. Local cerebral blood flow values were determined utilizing stable xenon contrasted computed tomography and volumes for brain parenchyma were estimated from ratios of volumes of infarcted brain plus cerebrospinal fluid/total intracranial volume measured on the same CT slices among two groups of patients, one with mild and the other with severe MID. A total of 26 demented patients with multiple cerebral infarcts were divided into 2 index groups, one with mild and the other with severe MID (mild MID, CCSE greater than or equal to 15, n = 16; severe MID, CCSE less than 15, n = 10). Results were compared with similar measures among age-matched neurologically normal volunteers (n = 14). Ratios for volumes of lost brain parenchyma were significantly higher among severe MID patients than among age-matched normal volunteers, whereas estimates of brain loss among patients with mild MID did not differ from elderly normal volunteers. In patients with mild MID, LCBF values for cortical gray matter were decreased compared with age-matched normal volunteers. Results suggest that chronic cerebral hypoperfusion is an important determinant for mild dementia among patients in the early stages of MID, but volumes of lost cerebral parenchyma due to cerebral infarctions is an important determinant for advanced stages of MID. PMID- 1856731 TI - Anti-presynaptic membrane receptor antibodies in myasthenia gravis. AB - Myasthenia gravis (MG) is considered as an autoimmune disease of neuromuscular junction resulting from antibodies directed to acetylcholine receptors (AChR). We describe the use of beta-bungarotoxin (beta-BuTx) and alpha-bungarotoxin (alpha BuTx) to capture their corresponding proteins from preparation of crude human muscle receptor. beta-BuTx binds to presynaptic membrane receptor (PsmR) of the whole receptor fraction, while alpha-BuTx binds to AchR. The captured proteins were used as antigen in ELISA to detect antibodies to PsmR and to AchR in sera from 82 Chinese patients with MG and in controls. In MG, antibodies to PsmR only were detected in 13%, to AchR only in 11% and both to PsmR and AchR in 54%. Only 3 of 50 patients with other neurological diseases and none of 50 healthy subjects had these antibodies. Specificity tests for antibodies showed that the detection systems which we used are specific and confident. No correlation was found between antibody levels and clinical status. The significance of the PsmR antibodies in the pathogenesis of MG is unknown. We suggest that myasthenia gravis is not only due to damage of the postsynaptic membrane, but of presynaptic structures as well. PMID- 1856732 TI - Increased frequency of chromosome aberrations in long-term cultured cerebrospinal fluid lymphocytes of patients with multiple sclerosis. AB - A method employing long-term lymphocyte culturing was developed to study chromosome aberrations in samples with very few cells. It was used to examine lymphocytes from the cerebrospinal fluid (CSF) and peripheral blood (PB) in 23 patients with clinically definite multiple sclerosis (MS), nine patients with other neurological diseases (OND), and eight healthy individuals. MS patients had significantly more aberrations in CSF lymphocytes than in PB lymphocytes (6.4 vs 4.1; P = 0.003). In contrast, no such difference was noted among patients with OND (3.8 vs. 3.7; P = 0.89) or healthy controls (3.6 vs 3.5; P = 0.90). CSF lymphocytes from MS patients had more aberrations than CSF lymphocytes from healthy controls (P = 0.012), but there was no difference between PB lymphocytes from MS patients and controls (P = 0.58). The patients with OND were similar to healthy controls both in CSF (3.8 vs 3.6; P = 0.91) and PB lymphocytes (3.7 vs 3.5; P = 0.90). PMID- 1856733 TI - Search for antibodies to neutral glycolipids in sera of patients with Guillain Barre syndrome. AB - Sera from 54 patients with Guillain-Barre syndrome (GBS), 34 patients with other neurological diseases (OND) and 32 healthy controls were tested for antibodies to total lipid fractions and higher neutral glycolipid fractions isolated from human and dog nerves, purified Forssman glycolipid and a panel of purified neutral glycolipids by both an enzyme-linked immunosorbent assay (ELISA) and a thin-layer chromatogram (TLC)-overlay technique. IgM and IgG antibodies to total lipid fractions, as well as to galactocerebroside, ceramide dihexoside, ceramide trihexoside, and globoside were not significantly elevated in the sera of GBS patients as compared to controls. High levels of anti-asialo-GM1 IgG antibodies, however, were detected in 6 of 54 (11%) GBS patients and 1 of 30 (3%) OND patients. Intense reactivity with purified Forssman glycolipid and a number of glycolipid antigens in higher neutral glycolipid enriched fractions of human cauda equina and dog sciatic nerves was noted by TLC-immunostaining in many GBS and control sera. Although the levels of anti-Forssman IgM were significantly decreased in GBS sera compared with normal sera (P less than 0.05) and OND sera (P less than 0.02), the levels of anti-Forssman IgG antibodies were not significantly different. With the possible exception of IgG antibodies to asialo GM1, our results suggest that serum antibodies against Forssman glycolipid and neutral glycolipids are not significantly elevated in GBS patients and, thus, are unlikely to play an important role in the pathogenesis of this disease. PMID- 1856734 TI - A case of adult onset pure pallidal degeneration. I. Clinical manifestations and neuropathological observations. AB - We present a case of adult onset progressive neurodegenerative disease with a selective involvement in the globus pallidus (GP). The main symptom was extreme slowness in motion without rigidity, which was distinct from akinesia of parkinsonism. Dystonic posture developed in neck and fingers and mild rigidospasticity appeared in a later stage. Neuropathological examination shows a selective neuronal loss with gliosis in GP and degeneration of the efferent fibers. Although the subthalamic nucleus is slightly atrophic with minimal gliosis, there is no neuronal loss in the nucleus. The rest of the structures are pathologically insignificant. Because the pathological change is confined to GP neurons and their efferent fibers, we think that the marked slowness in motion and dystonic posture are ascribable to the selective GP lesion. A degenerative neurological disorder preferentially involved in GP was reported as pure pallidal degeneration (PPD). The onset of the PPD was in the first or second decades and the main symptoms were choreoathetosis, torsion dystonia and progressive rigidity. These distinct clinical features seemed to distinguish the present case from the previously described PPD. Therefore, we would like to call our case "adult onset" PPD. Clinicopathological correlation is discussed. PMID- 1856735 TI - A short plasma exchange protocol is effective in severe myasthenia gravis. AB - Plasma exchange has been reported to be a successful therapeutic procedure for the treatment of severely compromised myasthenic patients, but the optimal regimen in terms of costs or clinical benefit has not so far been determined. We have investigated the efficacy of a short plasmapheresis protocol of two exchanges 1 day apart in a series of 70 patients with severe forms of myasthenia gravis. Patients were evaluated before and 7 days after the first exchange. A positive outcome was observed in 70% of the plasma exchange cycles performed. Disease severity did not seem to be a negative prognostic factor for the efficacy of this short protocol, which was well tolerated by patients. In only 1 case were major side-effects observed. In spite of its short duration, the exchange treatment plus concomitant immunosuppressive drug therapy was not followed by early clinical deterioration. PMID- 1856736 TI - The effect of zidovudine on chronic myelopathy associated with HTLV-1. PMID- 1856737 TI - Induction of seizures by transcranial magnetic stimulation in epileptic patients. PMID- 1856738 TI - Glial cells and the new neurology. A meeting report on a conference entitled "Glial neuronal interaction", 4-7 September 1990, Cambridge, UK. PMID- 1856739 TI - Transplantation of embryonic dopamine neurons: what we know from rats. PMID- 1856741 TI - Assessment of proliferative potential in gliomatosis cerebri. AB - The proliferative potential of neoplastic cells in two cases of gliomatosis cerebri was investigated by a combined staining technique, a one-step silver colloid method for nucleolar organizer region-associated protein (AgNOR) and immunohistochemistry for fibrillary acidic protein (GFAP). The neoplastic cells in the two cases had an abnormal shape and showed positive GFAP immunostaining in their cytoplasm. The numbers of AgNORs were counted in central and peripheral lesions of the neoplastic field in each case. The mean AgNOR scores in neoplastic cells were almost the same as those of nonneoplastic astrocytes in both the central and the peripheral lesions. These values were almost equal to the AgNOR score of low-grade gliomas. These findings indicate that gliomatosis cerebri has an invasive character in the central nervous system and often shows a malignant tendency, but its proliferative potential is significantly lower than that of high-grade gliomas. PMID- 1856740 TI - Antibodies in sera from patients with inflammatory demyelinating polyradiculoneuropathy react with ganglioside LM1 and sulphatide of peripheral nerve myelin. AB - Sera from 23 patients with acute Guillain Barre syndrome (GBS), 15 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and from 40 age matched blood donors were analysed for antibodies to acidic glycosphingolipids from human brain and peripheral nerve. Antibodies to ganglioside LM1, the major ganglioside of peripheral nerve myelin. were found in 43% of GBS and in 67% of CIDP patients' sera, and in 20% of the blood donors. However, antisulphatide antibodies were detected in 65% and 87% of the sera from GBS and CIDP patients, respectively, but only in 15% of the control sera. Sulphatide is the major acidic glycosphingolipid in myelin and its concentration in peripheral nerve myelin is 100 times higher than that of LM1. The high frequency of LM1 and, in particular of sulphatide antibodies, might thus be relevant to the pathogenesis of the GBS and CIDP. PMID- 1856742 TI - A community-based study of incidence, risk factors and outcome of transient ischaemic attacks in Umbria, Italy: the SEPIVAC study. AB - The SEPIVAC study is a community-based epidemiological survey of incidence and outcome of transient ischaemic attacks (TIAs) and strokes in the territory of the 6th Local Health Unit, Umbria, Italy, where 49,218 people live, from 1 September 1986 to 31 August 1989. All cases were registered with the study either by notification from general practitioners (GPs) or by a check of hospital admission within the study area and in the two hospitals of Perugia. There were 94 incident cases of TIAs (45 males, 49 females), thus giving a crude rate of 0.64 per 1000 per year [95% conficence intervals (CI) 0.52/0.78]. The rate adjusted to the European population is 0.42 (CI 0.33/0.54). Mean age was 69.4 years, and females were significantly older than males. The weighted relative risk for males was 1.19 (CI 0.79/1.79). Thirty-one patients were treated at home by their GPs. Females had hypertension more frequently than males, whereas males smoked more frequently; we did not find any other statistically significant difference in the distribution of risk factors. Twelve patients out of 58 who had CT had an infarct, and 29 out of 54 submitted to Doppler ultrasonography had carotid stenosis. At 1 month, 4 patients had suffered an ischaemic stroke, 1 of whom died. At 6 months, 3 further strokes and 2 further deaths (1 due to myocardial infarction) had occurred. PMID- 1856744 TI - An investigation into attrition of dental hygienists from the work force. PMID- 1856743 TI - Smoking and hypertension: risk factors for carotid stenosis. AB - The prevalence of smoking, hypertension and diabetes mellitus was assessed in 221 patients suffering from internal carotid stenosis and compared with the prevalences in two sex- and age-matched control groups composed of subjects having normal Doppler findings and from non-neurological outpatients. Of the subjects with carotid stenosis 27.6% were hypertensive smokers in comparison with 9.5% and 17.2% in the two control groups. The difference of the stenosis cohort from the two control groups was significant (P less than 0.01 and P = 0.016 respectively). There was no statistically significant differences between the occurrence of diabetes and hypertension in non-smokers and patients who smoked. In 394 investigated patients suffering from carotid stenosis or occlusion an obstruction index, based on the Doppler shift frequency, was calculated. This index was lowest in the normotensive smokers [corrected]. It was only insignificantly higher in the hypertensive non-smokers but significantly so in the normotensive smokers. The index was highest in the hypertensive smokers [corrected]. It was concluded that cigarette smoking, especially if associated with hypertension, is a determinant risk factor for carotid stenosis and occlusion. PMID- 1856745 TI - Can state licensing boards do better? PMID- 1856746 TI - Factors affecting participation in external degree completion programs. AB - Although many dental hygienists have considered pursuing a baccalaureate degree, many barriers intervene to prevent accomplishment of this goal. The external degree is one option that could be available to overcome some of the barriers to accessibility. An external program is one that makes education accessible to students in nontraditional ways. A characteristic of these programs is that students can usually pursue academic credit toward a degree without being physically present on the degree-granting campus for the majority of the program. This paper reports the results of a 1988 survey of certificate and associate degree dental hygienists' interest in an external baccalaureate degree completion program. A questionnaire was mailed to 213 certificate and associate degree dental hygienists in Tennessee who had expressed an interest in degree completion. Two hundred six questionnaires were returned for a response rate of 96.7%. In order to determine the potential success of such programs, the following factors were explored: the motivations or reasons for participating; program design factors that might encourage or deter participation; degree of employer support; and individual characteristics relevant to participation, such as personal commitment and demographic information. Geographic location, flexibility in scheduling, and accessibility to course work were the program design factors most important to the likely participants. Likely participants indicated that they wanted to return to complete their baccalaureate degrees for personal satisfaction, for the status of the degree, and to increase their knowledge and skill in dental hygiene. They indicated that they did not want to change the focus of their careers. The area of study rated as most important was advanced clinical dental hygiene. The likely participants were found to resemble other nontraditional students. They averaged 34 years of age, were married with children living at home, and were able to study on a part-time basis only. The analysis of the data obtained from the questionnaire led to the conclusion that external program design factors would be essential for most certificate and associate degree dental hygienists to participate in a baccalaureate degree completion program. PMID- 1856747 TI - KVP meter errors induced by plastic wrap. AB - The purpose of this study was to determine whether erroneous kVp meter readings, induced by plastic wrap, affected the actual kVp (output) of a dental X-ray machine. To evaluate the effect of plastic wrap on dental X-ray machine kVp meters, a radiation output device was used to measure output in mR/ma.s. An intraoral dental X-ray unit (S.S. White Model #90W) was used to make the exposures. First, the kVp meter was not covered with plastic wrap and output readings were recorded at various kVp settings with the milliamperage and time held constant. Secondly, the same kVp settings were selected before the plastic wrap was placed. Milliamperage and time were again held to the same constant. The X-ray console was then covered with plastic wrap prior to measuring the output for each kVp. The wrap possessed a static charge. This charge induced erroneous kVp meter readings. Out-put readings at the various induced kVp settings were then recorded. A kVp of 50 with no wrap present resulted in the same output as a kVp of 50 induced to read 40 or 60 kVp by the presence of wrap. Similar results were obtained at other kVp settings. This indicates that the plastic wrap influences only the kVp meter needle and not the actual kilovoltage of the X-ray machine. Dental X-ray machine operators should select kVp meter readings prior to placing plastic wrap and should not adjust initial settings if the meter is deflected later by the presence of wrap. The use of such a procedure will result in proper exposures, fewer retakes, and less patient radiation. If plastic wrap leads to consistent exposure errors, clinicians may wish to use a 0.5% sodium hypochlorite disinfectant as an alternative to the barrier technique. PMID- 1856748 TI - AIDS education in dental hygiene programs in the United States and Canada. AB - The purpose of this study was to determine school policies, acquired immunodeficiency syndrome (AIDS) -related content areas, and curricula hours devoted to AIDS study in accredited schools of dental hygiene. The sample included all 217 accredited programs in the United States and Canada. Eighty-five percent (184) of the sample completed the 10-item questionnaire. Results reveal that 98% of the respondents include information on the oral disease manifestations of AIDS in their curricula. Over 70% of the sample include material on AIDS etiology, incidence, epidemiology, general clinical symptoms, HIV testing, attitudes and fears of practitioners, and dental hygiene care and treatment. Most schools spend four to 10 curricula hours covering general content on AIDS. Over one-half of the respondents require students to use special infection control protocols. When treating known infectious disease patients. Most schools responding have policies which favor student treatment of HIV positive patients, and the majority of the respondents do not have a written policy concerning admitting students who are HIV-positive. Less than 30% of the schools teach financing of AIDS-related healthcare or AIDS resources. One respondent admitted not including any AIDS information in the curricula. Results suggest that most accredited schools of dental hygiene in the United States and Canada should include additional information on AIDS in their curricula to ensure student competency in providing oral healthcare to HIV-infected individuals. PMID- 1856749 TI - Personality characteristics and career choice among dental hygiene students enrolled in non-baccalaureate programs. AB - The purpose of this study was (1) to determine the personality characteristics of dental hygiene students, and (2) to determine if dental hygiene students have personality characteristics similar to those of the general population. Students from three non-baccalaureate degree programs were requested to complete a demographic questionnaire and the Myers-Briggs Type Indicator (MBTI). Eighty-six percent of the 124 students responded. The MBTI data was analyzed using frequency distributions, electivity indices, and chi-square analyses. Individuals categorized as ESFJ (extraversion, sensing, feeling, and judging) and ISFJ (introversion, sensing, feeling, and judging), two of the possible 16 MBTI personality types, comprised 39% of the sample. These two personality types were found in significantly greater numbers in the study population than in a random sample of the general population. People with the ISTJ (introversion, sensing, thinking, and judging), INFP (introversion, intuition, feeling, and perception), and INFJ (introversion, intuition, feeling, and judging) MBTI personality types were found in significantly lesser numbers in the study population than in a random sample of the general population. This suggests that dental hygiene students are not drawn at random from the general population. Self-knowledge, as measured by the MBTI, could prove beneficial for prospective dental hygiene students, students currently enrolled in dental hygiene programs, and educators. Additionally, practicing dental hygienists might find that the MBTI personality assessment results could help them identify career paths in the field that would enhance career fulfillment, thereby increasing the retention of professionals in the field. PMID- 1856750 TI - Identifying hearing impairment among older adults. AB - A survey of older-young and younger-old adults (ages 45-64) was conducted to identify the existence of a hearing impairment as described by a self administered hearing test. Seventy of 96 surveys were returned yielding a response rate of 73%. The results indicated that the younger age group (ages 45 54) scored lower on the hearing loss test than the older age group (ages 55-64), suggesting a greater degree of loss in older adults, and females scored lower suggesting a greater degree of hearing loss in males. Responses also revealed a positive correlation of .77% between the respondent's perception of ability to hear and a relative/friend's perception of the respondent's ability to hear. PMID- 1856751 TI - Ovarian hormones and gingivitis. PMID- 1856752 TI - Assessing periodontal disease activity. The role of bacteriological, immunological, and DNA assays. PMID- 1856753 TI - A model for integrating student and faculty research. AB - Research productivity is a major criterion for measuring academic performance in most universities today. Because of heavy teaching loads, dental hygiene faculty often have difficulty allocating adequate time to conduct research. Thus, professional advancement might be impeded since faculty may be less productive in the research area than is desired by the academic unit. A method that might assist dental hygiene faculty to become more research productive focuses on student involvement with faculty on collaborative research projects. The purpose of this article is to describe a model designed to enhance the integration of faculty and student research in dental hygiene and to explain the benefits inherent in dental hygiene student involvement with faculty on collaborative research projects. PMID- 1856754 TI - Volunteers. PMID- 1856755 TI - High-tech removal of fractured posts, silver points and separated devices. AB - Situations sometimes arise in the endodontic treatment of teeth when it is necessary to remove intact or fractured posts, silver points or separated files. It is the purpose of this paper to discuss the problems and solutions associated with retreatment of such cases. PMID- 1856756 TI - Ectopic eruption of the first permanent molar. AB - It is possible to resolve an ectopic eruption with the placement of a steel crown on the second primary molar. This article is a review of the recent literature and the presentation of three cases showing the resolution of ectopic molars using steel crowns. PMID- 1856757 TI - Correction of an anterior crossbite with a steel crown. PMID- 1856758 TI - Dental complications of bulimia nervosa. PMID- 1856759 TI - Does your practice need another doctor? PMID- 1856760 TI - Bereavement. Who counsels the counselor? PMID- 1856761 TI - Antepartum fetal assessment. A nurse-midwifery perspective. AB - This article provides an in-depth review of the most current antepartum fetal assessment techniques. Included in this review are both low- and high-technology methods, such as fetal movement counting, nonstress tests, vibroacoustic stimulation, auscultated acceleration tests, contraction stress tests, amniotic fluid index, biophysical profiles, and Doppler velocimetry. The interpretation of antepartum testing using screening test validity concepts is addressed, as is the current and emerging role of the nurse-midwife in fetal assessment. By integrating content on maternal and fetal physiology, including a critical review of current literature, together with relevant clinical information, including protocols, this article provides a useful guide to fetal assessment for nurse midwives. PMID- 1856762 TI - Maternal health practices and complications of term labor. AB - The purpose of this study was to examine the relationships between a healthful life-style, demonstrated by selected health practices, and complications in term labor. A sample of 493 clinic patients were interviewed at term, but prior to the onset of labor, regarding nine health practices. In a logistic regression, three of the nine practices examined were associated with significant changes in the rate of intrapartum complications: smokers experienced fewer intrapartum problems, whereas those with excess weight for height at conception and those whose gestational weight gain exceeded 40 pounds experienced an increased incidence of complications. PMID- 1856763 TI - Development and validation of the Nurse-Midwifery Clinical Data Set. AB - This paper describes the procedures used to develop and validate the Nurse Midwifery Clinical Data Set (NMCDS), a uniform, standardized tool for the purpose of data collection about midwifery clinical practice. The instrument was developed under the auspices of the ACNM Division of Research, and it was shown to be valid for the purposes of quality assessment data collection through the use of specific instrument development and field testing procedures. These procedures included consensus panel development, expert panel review, standardization, feasibility analysis, and validation through comparison with previous outcome data and record review. The 1990 version of the NMCDS is appended to the article. PMID- 1856764 TI - Political participation behaviors of nurse-midwives. AB - Political participation, which is promoted by nurse-midwifery leaders, is a widely studied topic in this country. Yet, there is little data that describes political participation among health care providers such as nurse-midwives. The descriptive findings presented here are from a national survey of a random sample of members of the American College of Nurse-Midwives. The data indicate that nurse-midwives are inclined to be liberal and Democrats and they believe that individuals such as themselves can influence governmental activities. As in the general population of the country, the electoral act of voting is the predominant political activity. Nurse-midwives are more apt to demonstrate nonelectoral political behaviors in regard to women's issues. Overall, there is a general assumption that the representatives of the ACNM membership maintain the responsibility for political action. PMID- 1856766 TI - Midwifery education and research in the future. AB - This paper is adapted from a plenary lecture presented at the 22nd International Congress, International Confederation of Midwives, Kobe, Japan, October 11, 1990. Midwifery education and research in the past, present, and future are discussed. Special emphasis is placed on innovation in midwifery education to address more adequately the worldwide concern about safe motherhood. Midwifery research and the integral components of information and inquiry are also discussed, with emphasis on five major areas in need of further research. Collaborative education and research are explored from both an interdisciplinary and an international perspective. PMID- 1856765 TI - Comparison between different perineal outcomes on tissue healing. AB - Perineal healing was compared between 181 women with episiotomies and 186 women without episiotomies at one to two weeks after delivery. Subjects were medically indigent low-risk women who had normal spontaneous vaginal deliveries at the same tertiary-care hospital. Maternal age, race, parity, and birth weight did not have an independent effect on perineal healing. Perineal outcome at delivery and length of second stage exhibited a significant relationship with perineal healing. Overall, there was a 4.9% incidence of delayed perineal healing due to wound separation or clinical infection. In the episiotomy group, 7.7% of the subjects experienced delayed perineal healing compared with 2.2% in the no episiotomy group. This was statistically significant using Pearson chi-square analysis. These results suggest that women without episiotomies exhibit better perineal healing than women with episiotomies. PMID- 1856767 TI - Comanagement of the patient on subcutaneous terbutaline pump therapy. AB - The subcutaneous terbutaline pump is a new modality available for pharmacologic treatment of preterm labor. Because nurse-midwives may be involved in the care of women on this therapy, an overview of terbutaline pharmacology, pump development, and advantages versus disadvantages of this therapy is provided. Initiation of therapy in the appropriate patient is described. Outpatient therapy is the goal for these women, and the nurse-midwife may appropriately comanage this aspect of care. Guidelines are presented for physical and psychosocial care. PMID- 1856768 TI - Reassessment of the metabolic effects of oral contraceptives. PMID- 1856769 TI - Facial flushing in children: a variant of the auriculo-temporal syndrome. AB - Duphenix in 1757 has been credited with describing the first case of gustatory sweating which occurred after drainage of a parotid abscess. Later, Baillarger reported a case in which the sweating occurred on both sides because of bilateral parotitis. In 1923, Frey reported a case of gustatory sweating caused by an infected bullet wound of the parotid. She noted that the sweating coincided with the skin distribution of the auriculo-temporal nerve. Since her report, gustatory sweating has also been known as the "Auriculo-temporal Syndrome" or "Frey's Syndrome." PMID- 1856771 TI - Dental photography with a professional approach. PMID- 1856770 TI - Indiana infant-toddler dental care survey. AB - The purpose of this project was to survey Indiana dentists concerning dental care for Indiana infants and toddlers. Dental care issues covered were the age for a child's first dental visit, frequency of rampant or nursing caries cases examined, and dental referral sources for infants and toddlers. The survey also helped determine the dentist's perception of parents' attitudes toward services recommended by the dentist. A twelve question survey was mailed to 2006 general and pediatric dentists in the State of Indiana. The results of the survey were: 1. A large percentage of Indiana dental practitioners do not recommend the first dental visit or examine children for their dental visit until the child is more than one year of age. 2. A majority of Indiana dental practitioners see children with nursing caries or rampant caries on a monthly basis. 3. The majority of Indiana dental practitioners refer children with nursing caries to pediatric dentists for treatment. 4. Although the full treatment plan may undergo some modification based on various parental concerns, a majority of practitioners do not experience difficulty in obtaining treatment plan acceptance for nursing or rampant caries cases. PMID- 1856772 TI - Shortened dental arches and periodontal support. AB - The periodontal support of subjects with shortened dental arches (SDA, n = 74), and of subjects with SDA and free-end removable partial dentures in the lower jaw (SDA and RPD, n = 25) was compared with that of subjects with complete dental arches (CDA, n = 72). The periodontal support was determined by tooth mobility and alveolar bone height, measured on a radiograph, of the distal alveolar bone of the premolars. Significant differences in tooth mobility were found between the three groups of subjects. The relative bone height showed a trend towards lower values for the SDA group and the SDA and RPD group. For some teeth these differences were significant. Premolars that are the most posteriorly located occluding teeth in the dental arch tend to have a lower relative alveolar bone height than premolars in an intermediate location. This effect is more marked in the upper jaw than in the lower jaw. Premolars in the lower jaw, that serve as abutment teeth for free-end RPDs, tend to show lower values for the relative bone height. It is concluded that the differences between the three groups with regard to the periodontal support are small. The large amount of crowns and bridges in both the SDA and SDA and RPD groups, and the dental history of these subjects, resulting in SDA, should be taken into account. However, as indicated by the periodontal breakdown of premolars in some subjects with SDA, the combination of an existing severe periodontal involvement and a SDA is considered to be an unfavourable situation. PMID- 1856773 TI - Porosity of pit and fissure sealants. AB - The aim of this study was to investigate the bulk porosity of a range of pit and fissure sealants. The following materials were included in the study: Concise White Sealant and Delton (chemically cured); Delton (visible light-cured); Helioseal, Visioseal and Prolite (visible light-cured with delivery from the bottle via cannule); Delton, Luma Seal and Prisma Shield (visible light-cured with syringe-type direct delivery systems). Five cylindrical samples, 7 mm in diameter and 1 mm in thickness, were prepared from each sealant and the following parameters were analysed in a computer-controlled mercury porosimeter: (i) total cumulative pore volume; (ii) specific surface area of pores; (iii) percentage total porosity (iv) bulk density; and (v) pore radius distribution. According to the results, the chemically cured sealants exhibited total cumulative pore volume, specific surface area of pores and total porosity. Significant differences were detected within the group of visible light-cured materials. The visible light-cured sealants with syringe-type delivery exhibited the lowest porosity. PMID- 1856774 TI - Masseteric post-stimulus EMG complex following mechanical stimulation of osseointegrated oral implants. AB - Periodontal receptors can be located in the periodontal ligament itself, the alveolar bone, the periosteum and the gingiva. The aim of the present study was to quantify the contribution of the periodontal ligament receptors in eliciting a reflex response in human masseter muscles. Surface EMG recordings were made in 17 human subjects, fully or partially edentulous, and all provided with osseointegrated oral implants ad modum Branemark. They maintained a constant clenching level. Mechanical stimulation of an oral implant in the upper central incisor region failed to elicit a reflex in fully edentulous subjects with oral implants in both jaws. The absence of a reflex response strongly suggests that the receptors in the periodontal ligament itself are mainly responsible for the reflex. Stimulation of the same area in subjects with oral implants in the upper jaw and natural teeth in the lower jaw elicited a reflex response in most subjects. Since they were instructed to clench in full habitual occlusion, transmission from the stimulated area to periodontal receptors of natural teeth is very probable. PMID- 1856775 TI - The prevalence of craniomandibular disorders in completely edentulous denture wearing subjects. AB - A total of 201 completely edentulous subjects taken consecutively from the waiting list of the Royal Dental Hospital of Melbourne were examined. Data were obtained from the dental history and anamnestic and clinical examinations. Analysis revealed that parafunctional habits were prevalent among complete denture wearers, and that elderly complete denture wearers potentially present more signs and symptoms of craniomandibular disorders than do younger subjects. PMID- 1856776 TI - Aetiological factors of craniomandibular disorders in completely edentulous denture-wearing patients. AB - A total of 201 completely edentulous patients awaiting treatment for new complete dentures at the Royal Dental Hospital of Melbourne were examined for signs and symptoms of craniomandibular disorders, and a history was taken regarding their dentures. Statistical analysis by means of Student's t-test showed that the only reliable indicator of craniomandibular disorder was the patient's sex, i.e. female subjects tend to show more symptoms of craniomandibular disorders than male subjects. When regression and multiple regression analyses were applied, it was found that subjects with a history of fewer sets of complete dentures worn appeared to be correlated with an increase in the number of signs and symptoms of craniomandibular disorders. However, this correlation had a weak predictive power, although it was significant enough to indicate that such a relationship could exist in the general population. PMID- 1856777 TI - Influence of an occlusal splint on integrated electromyography of the masseter muscles. AB - In order to examine the effect of an occlusal splint on the integrated electromyography (EMG) of the masticatory muscles, EMG of bilateral masseter muscles of 23 patients with temporomandibular joint disturbance syndrome (TMJDS), with and without an occlusal splint, was measured and integrated on line during maximum clenching. It was found that the integrated myoelectrical value of the masseter muscle on the involved and non-involved side was reduced with the occlusal splint. The absolute difference between integrated myoelectrical values in the left and right masseter muscles was reduced with an occlusal splint, but the relative difference remained virtually unchanged. These results indicate that the occlusal splint can decrease masseter muscle activity and thus exert a therapeutic effect. PMID- 1856778 TI - Wedges in restorative dentistry: principles and applications. AB - Overhanging margins of proximal restorations are a well-known, iatrogenic cause of periodontal pathology. The high incidence of such findings in Western societies should arose the concern of the dental community. However, overhanging margins represent only part of the iatrogenic problem created by the misuse of wedges in restorative procedures. Other causes include incorrect proximal contouring, inadequate contact points and under- or overfilling the restorative material. The understanding of the variables associated with wedge selection and positioning has a major role to play in the prevention of iatrogenic periodontal pathology associated with restorative procedures. It is concluded that: (i) the occlusion of the matrix band to the remaining healthy tooth structure of the gingival cavosurface line angle should be achieved solely by the correct application of the wedges; (ii) the effect of the wedges on the proximal contour and contact area should be carefully re-evaluated prior to insertion of the restorative material; (iii) various sizes and shapes of wedges and a sharp knife for carving must be readily available. PMID- 1856779 TI - Occlusal force pattern during rhythmic human tapping movement. AB - The dynamic occlusal force patterns associated with the performance of rhythmic tapping movement were analysed in normal subjects, who were instructed to make tapping movements at four frequencies, 2, 2.5, 3.3 and 5 Hz, with as constant a magnitude of force as possible. The occlusal force recorded by an intra-oral customized device showed a triphasic pattern which could be divided into two components, and this pattern was more clearly defined during slower tapping movements. Of the two components, the first was relatively stable, regardless of changes in tapping frequency, while the second was highly dependent on the tapping cycle duration, and its duration was shortened with increases in tapping frequency. Furthermore, there was a significant correlation between the changes in the occlusal power phase and those in the burst duration of the masseter EMG simultaneously recorded by a pair of surface electrodes. On the basis of these findings, it is suggested that the tapping rhythm is modulated by the duration of the occlusal power phase and the associated jaw elevator muscle activity. PMID- 1856780 TI - Power spectral analysis of occlusal sounds of natural dentition subjects. AB - Fifteen subjects with complete natural dentitions were selected for investigation of their occlusal sounds on the left and right sides by means of power spectral analysis. It was found that the occlusal sounds consisted of various frequency components. Their mean power frequencies (MPF) and frequencies at 10, 20, 50, 80 and 90% of cumulative power (F10, F20, F50, F80, F90) on the left and right sides were almost identical (P greater than 0.05). The correlation coefficients between MPF and F50, MPF and F50 with the others were high. The results indicate that F20, MPF or F50 and F80 may be used as indices to describe the power spectral shape, and that power spectral analysis of occlusal sounds may be used as a contribution to diagnosis of occlusal conditions. PMID- 1856781 TI - National Toxicology program report on fluoride and cancer. PMID- 1856782 TI - Management of a patient with a painful, erosive, mucosal condition. PMID- 1856783 TI - Breast prostheses: a critical review. PMID- 1856784 TI - Polyurethane-covered mammary prosthesis: a nine year follow-up assessment. AB - We have examined ten tissue capsules from patients ranging from five months to nine years of mammary implantation. Contrary to published reports of polyurethane foam "fragmentation" or "disappearance" in the capsules evaluated, the polyurethane foam was still present and embedded in the surrounding tissue capsule. The foam was nearly always invisible by gross observation, or manual palpation. Only after enzymatic digestion of the tissue capsule did the foam become clearly visible as continuous sheets. ESCA analyses show that explanted foams are devoid of nitrogen peaks. Only carbon, oxygen and silicone signals are observed. The same foams do show nitrogen peaks (due to urethane linkages) when probed by FTIR. Since ESCA only analyzes the first 40-50 Angstroms of a surface, we believe that a "protective coating" composed of soft segments has formed. Beneath this "coating" the original polyurethane composition is still present as evidenced by FTIR analysis. Three possible explanations are advanced: (1) The surface hydrolysis, which takes place within the soft segment of the polyurethane polymer, results in the formation of oligomer(s). These oligomers, devoid of urethane linkages, appear to protect the polymer from further bioresorption, by significantly retarding the rate of additional surface hydrolysis. (2) Chain cleavage occurs in the soft segment producing a hydrophilic polyester chain end which orients into the interfacial area. These chain ends then produce a skin effect which increases the distance from the surface to the hard segments, or urethane-containing linkages. (3) Macromolecular motion in the soft segment phases of the polymer could be reorienting under the influence of the in vivo environment, thus producing a surface layer or "coating" which is predominantly soft segment in composition. Regardless of which of the three hypotheses proves to be most plausible, we interpret the data as showing that the polyurethane foam cover undergoes very slow bioresorption, even after 9 years of human implantation. The data further suggests that the in vivo surface of the polyurethane foam cover is biocompatible and interfacial interactions with inflammatory cells are downregulated or reduced because of the apparent biocompatibility of the material. PMID- 1856785 TI - An assessment of 2,4 TDA formation from Surgitek polyurethane foam under simulated physiological conditions. AB - Samples of polyurethane foam used in the manufacture of mammary prostheses were enzymatically treated for a total of thirty days. Papain (a plant thiol endopeptidase which has similar activity to the human lysosomal enzyme cathepsin B) was our enzyme of choice since it has both amidase as well as esterase activity. The experiment was conducted under physiological conditions closely simulating the microenvironment likely to be found around an implanted mammary prosthesis. In our tests, 2,4 TDA was formed during enzymatic attack of this TDI based polyurethane foam for the first four (4) days, reaching a maximum of 8.3 parts per million. After the initial burst, no further TDA was observed within the limits of detection of the experiment (10 parts per billion). Based on standard risk assessment, this amount of TDA translates into a risk of developing cancer of one in four hundred million. PMID- 1856786 TI - Time course of wound healing. AB - Wound healing is a special kind of inflammation. Undisturbed wound healing is subject to a fixed time schedule of biochemical and cellular events. It is virtually impossible to deal with the time course of wound healing without describing the cellular and non-cellular events involved. The activity and mode of cell action after injury are coordinated by spatial and chronological factors, as well as by different mediators and cell-cell interacting signals. During wound healing the sequence of different signals and message substances, such as mediators of inflammation, fulfill a key function in wound repair. The report describes the time course of healing and the control of cellular events by different mediators and cell interactions. Emphasis is placed on temporal aspects, including the various signals leading to typical cellular events in wound healing. PMID- 1856787 TI - In vitro maturation of mononuclear phagocytes and susceptibility to HIV-1 infection. AB - In the present report, we have studied the in vitro transition of normal blood monocytes to macrophages by changes in cell morphology, and the expression of surface antigens with a panel of monoclonal antibodies. The maturation process was accompanied by notable changes in cell-surface markers in a time-dependent manner. The percentage of cells expressing CD11c, ICAM-1, HLA-DR, and Fc receptor class III increased while the CD4 and CD35 expression was markedly decreased. After demonstrating that in vitro monocytes mature to macrophages in a recognizable manner, we studied the susceptibility to HIV-1 infection at time points representing different stages of cell maturation. The results show that monocyte/macrophages are susceptible to HIV-1 infection at all stages of differentiation. However, the kinetics of virus replication depends on the degree of maturation at the time of infection. Two major patterns of replication were observed: Infection of monocytes resulted in efficient virus production measurable by reverse transcriptase activity in culture supernatant, whereas infection of fully differentiated macrophages yielded low but sustained virus release only demonstrable by p24 antigen assay. We were not able to detect differences in the capacity of the virus to infect and replicate in monocyte/macrophages with respect to cellular origin of the virus isolate and whether the viruses were laboratory-adapted strains or low-passaged patient isolates. PMID- 1856788 TI - Transepithelial transport of HIV-1 by intestinal M cells: a mechanism for transmission of AIDS. AB - This study was designed to determine whether human immunodeficiency virus type 1 (HIV-1) might enter the host by penetrating epithelial barriers through antigen transporting M cells in lymphoid follicle-associated epithelia. Interaction of HIV-1 with epithelial cells was examined using mucosal explants from Peyer's patches of mice and rabbits. HIV-1 adhered to the luminal membranes of M cells of both species, and was endocytosed and delivered to intraepithelial spaces containing lymphocytes and macrophages. These observations suggest that M cells, which are numerous in the human rectal mucosa, may efficiently deliver HIV-1 to target cells in mucosal lymphoid tissue, and that such transport may contribute to sexual transmission of AIDS. PMID- 1856789 TI - HIV-1 proviral copy number in blood mononuclear cells from AIDS patients on zidovudine therapy. AB - The effect of treatment with 400-1,200 mg/day of zidovudine (ZDV) on HIV DNA concentrations in patient peripheral blood mononuclear cells (PBMCs) was studied in six patients during a 5- to 14-month period of therapy. HIV DNA was measured in PBMCs at intervals using a recently developed quantitative polymerase chain reaction assay. The amount of HIV DNA ranged from 2,000 to 40,000 copies of provirus per microgram of cellular DNA. The HIV provirus copy number showed little change with time in five patients, and increased and then remained constant in one patient. Thus, prolonged treatment with ZDV does not decrease the levels of HIV DNA in PBMCs. PMID- 1856790 TI - Norepinephrine response in early HIV infection. AB - Norepinephrine response to a cold pressor test was investigated in 95 homosexual men in a longitudinal study of human immunodeficiency virus (HIV) infection. The baseline data obtained from 76 HIV+ and 19 HIV- subjects are included in this report. After the insertion of a venicatheter and following a 30 min rest, subjects immersed one of their hands in ice water for 2 min, and serial blood samples were obtained for the determination of catecholamine levels. The results show that the norepinephrine response in HIV+ subjects compared to that of HIV- subjects was blunted. Examination of the responses using linear and quadratic orthogonal polynomials suggested that these differences between the two groups were primarily a function of their rate of increase in norepinephrine levels. It was observed also that in HIV+ subjects, norepinephrine level peaked earlier than that in HIV- subjects. The data suggest that autonomic dysfunction is present in the early stages of HIV infection. PMID- 1856791 TI - Results of a one year longitudinal study of HIV antibody test notification from the San Francisco General Hospital cohort. AB - We examined the psychological impact of HIV antibody testing in 107 homosexual men in San Francisco. Seventy-eight percent of the seropositives but only 43% of the seronegatives correctly anticipated their results. Twelve months after notification (but not earlier), notified seropositives reported significantly greater increases in total distress than nonnotified controls. However, notified seronegatives demonstrated significantly lower levels of hopelessness than nonnotified controls at every follow-up assessment. Thus, knowledge of HIV antibody status appears to dispel a sense of gloom in persons who incorrectly believe themselves to be infected with HIV, but does not appear to induce significant distress in those whose expectation of a positive result is confirmed. Both groups reported lower distress than men with ARC or AIDS, suggesting that distress was related more to symptomatology than knowing antibody status. These results suggest the benefits of HIV testing for the considerable proportion of seronegative subjects believing themselves to be seropositive and should be weighted against the more limited induction of distress in seropositives who receive confirmation of their test result expectation. The benefits of testing are also supported by increasing knowledge of the usefulness of early intervention in HIV disease. PMID- 1856792 TI - Transfusion-associated AIDS cases in Europe: estimation of the incubation period distribution and prediction of future cases. AB - European data on transfusion-associated (TA) AIDS cases reported by December 31, 1989 have been analyzed using both parametric and nonparametric methods. Parametric estimates of the median incubation period of TA AIDS in adults vary from 6.5 to 11 years according to the type of distribution assumed (Weibull or gamma) and the latest year of diagnosis included (1987 or 1988). The latter finding may reflect a lengthening of the incubation period due to increasing treatment of HIV-infected patients prior to the development of AIDS. It is predicted that, by the end of 1991, between 2,000 and 3,000 cases of AIDS will have been diagnosed in Europe among adults infected by transfusion between 1978 and 1985 (when systematic screening of donated blood was introduced in most western countries). It is not possible, however, to predict how many further cases may arise among those transfused more recently in countries in which screening was introduced at a later date. PMID- 1856793 TI - Influence of host genotype on progression to AIDS among HIV-infected men. AB - To evaluate whether host genotype influences disease progression among persons infected with human immunodeficiency virus type 1 (HIV-1), molecular techniques were used to determine genotypes at immune response loci for 114 HIV-1-infected homosexual/bisexual white men in the San Francisco Men's Health Study. Candidate genes evaluated were HLA-DQA1 and -DRB1, complement C4A and C4B, alpha- and beta interferons, and the heavy chain of immunoglobulin gamma 1. Of the 114 men, 29 were asymptomatic, 21 were symptomatic men and AIDS patients (p = 0.02). Specifically, the HLA haplotype DRB1*0702-DQA1*0201 was associated with absence of symptoms (p = 0.003). Conversely, the frequency of the complement C4B-L allele was higher among patients with symptoms or with AIDS than among asymptomatic subjects (p = 0.02). These results suggest that genes in or near the major histocompatibility complex may influence the rate of disease progression among HIV-1-infected men. PMID- 1856794 TI - An evaluation of the polymerase chain reaction in HIV-1 seronegative men. AB - The apparent detection of human immunodeficiency virus (HIV-1) DNA by the polymerase chain reaction (PCR) in seronegative individuals has been the subject of great concern. In this study, 324 seronegative participants in the San Francisco Men's Health Study were evaluated for evidence of infection using a PCR testing algorithm with multiple amplifications targeting different regions of the HIV-1 genome. While most PCR reactions were negative, 8.6% of the specimens showed weak reactivity with one or more primer sets. However, all were negative with at least one primer set and no definitively positive specimens were identified. This study addressed the possibility that some of these PCR reactions might represent latent infection or abortive exposure, leaving residual integrated DNA, rather than false-positive reactions. The frequency of such reactions was determined in homosexual men who have been at risk for HIV-1 infection and in exclusively heterosexual men who have little or no past exposure. The results demonstrate an identical frequency and distribution of equivocal PCR reactions in both populations. Assuming that there is minimal HIV-1 infection among seronegative heterosexual men in San Francisco, we conclude that PCR testing does not provide evidence for a reservoir of occult HIV-1 infection in seronegative homosexual men. PMID- 1856795 TI - An update on Kaposi's sarcoma reporting in San Francisco. PMID- 1856796 TI - HIV-associated wasting. PMID- 1856797 TI - Patterns of secondary prophylaxis with aerosol pentamidine among persons with AIDS. PMID- 1856798 TI - Inactivation of human immunodeficiency virus (HIV) by low pH and pepsin. PMID- 1856799 TI - [Excitation-contraction coupling in skeletal muscle: characteristics of biphasic potassium contractures]. PMID- 1856800 TI - Ankylosing spondylitis and Klebsiella--the debate continues. PMID- 1856801 TI - Posttraumatic cartilage hypertrophy: edema or repair? PMID- 1856802 TI - Long acting drug combinations in rheumatoid arthritis: a formal overview. AB - We compared the benefits and risks of combinations of long acting antirheumatic drugs with those of the same drugs used singly in the treatment of rheumatoid arthritis. We searched the literature through MEDLINE (1966-89), Index Medicus (1956-65), Excerpta Medica (1982-89), Science Citation Index (1982-89), and bibliographic review of located articles. Of a total of 341 citations, we identified 7 prospective trials that specifically addressed the stated purpose. We independently assessed the quality of the selected trials, using published methodological criteria and summarized the effect of treatment on arthritis activity and the incidence of side effects. The trials we evaluated tested various drug combinations. Because of deficiencies in methods and reporting, only 3 trials had sufficient quality to yield strong or moderately strong evidence. None conclusively demonstrated benefit of a drug combination: 2 suggested such benefit, including 1 also suggesting increased toxicity; the 3rd suggested only increased toxicity. The other 4 trials yielded weak evidence to support both increased efficacy and toxicity. The advantages of any antirheumatic drug combination remain unproven. Because these advantages are likely to be modest, they can only be shown in rigorously designed trials enrolling large numbers of patients. Methods and reporting of antirheumatic drug trials should be standardized to allow combining of study results. PMID- 1856803 TI - Methotrexate in rheumatoid arthritis: effects on disease activity in a multicenter prospective study. AB - One hundred and twenty-three patients with rheumatoid arthritis (RA) who successfully completed a randomized trial comparing oral methotrexate (MTX) to auranofin enrolled in a longterm prospective study of oral MTX. Of the 91 patients who completed 24 months of therapy, a significant (p = 0.0001) improvement was noted compared to baseline in all clinical disease variables and the Westergren erythrocyte sedimentation rate (ESR). Marked improvement occurred in 94 (76%) and 98 (80%) of the patients in the joint pain/tenderness index and joint swelling index at the last evaluable visit (mean 26 months). Of the 77 patients with an elevated ESR at baseline, 29 (38%) patients normalized it (less than 20 mm/h) while receiving therapy (p less than 0.01). A significant reduction in prednisone dose was also seen. Adverse events occurred frequently but were generally mild in severity. Twenty-seven patients (22%) withdrew during the study. Four (3%) withdrew due to lack of efficacy, and 6 (5%) because of adverse experiences. The overall probability of continuing therapy in the study for 48 months was projected at 72%. This large prospective study supports the observation of earlier smaller studies that MTX is an effective drug in the treatment of RA. PMID- 1856804 TI - Low dose prednisone does not affect calcium homeostasis or bone density in postmenopausal women with rheumatoid arthritis. AB - To assess whether low doses of prednisone produce generalized alterations in skeletal homeostasis in rheumatoid arthritis (RA), indices of calcium metabolism and bone mineral density (BMD) were measured in 22 women with RA treated without or with prednisone (6.6 mg daily). Ionized and total calcium concentrations, intact parathyroid hormone (PTH) and osteocalcin levels were comparable in the 2 groups. BMD measurements in the lumbar spine, and proximal femur sites including the femoral neck, Ward's triangle, and trochanteric region were not significantly different in patients with RA treated without or with prednisone. In our experience low dose prednisone did not adversely affect indices of mineral metabolism, or bone density in RA. PMID- 1856805 TI - Prolactin and gonadal hormones during pregnancy in systemic lupus erythematosus. AB - We performed prospective hormonal studies in 9 patients (5 active and 4 inactive) with systemic lupus erythematosus (SLE) during pregnancy (Weeks 10 to 37). Nine healthy pregnant women and 5 patients with rheumatoid arthritis (RA) were used for comparison. Serum prolactin (PRL), testosterone and estradiol (E2) levels were determined by RIA. The patients with SLE showed higher serum PRL levels, the difference being statistically significant at Week 20, and reaching the highest levels at Weeks 30 to 40 (p = 0.05 when compared to healthy pregnant women). The 5 patients with active SLE had the highest serum PRL levels; one of these had fetal wastage. In active SLE the serum testosterone and E2 levels were decreased significantly from Weeks 10 to 30 compared with controls (p = 0.001). In patients with RA serum PRL levels, although higher than in controls, did not differ significantly, nor did the lower testosterone and E2 levels. We conclude that gonadal hormones and PRL changes observed in SLE are present also during pregnancy and may be related to fetal wastage and reactivation of disease. PMID- 1856806 TI - Specificity, sensitivity and diagnostic predictive value of selected laboratory generated autoantibody profiles in patients with connective tissue diseases. AB - We tested the hypothesis that the application of 5 laboratory generated serologic profiles facilitates the interpretation of individual autoantibodies in connective tissue diseases without loss of specificity, sensitivity or diagnostic predictive value. The predetermined laboratory generated autoantibody profiles were analyzed in 423 sera from patients with clinically diagnosed connective tissue diseases. All sera positive for one or more autoantibodies to a selected panel of nuclear antigens could be segregated into one of 5 profiles. The distribution of individual autoantibodies and profiles in the sera of patients with various connective tissue diseases were compared in terms of their respective diagnostic predictive value and sensitivity. The application of these profiles improved the sensitivity and diagnostic predictive value of these tests when compared to individual autoantibodies without loss of specificity, thus aiding clinical interpretation. PMID- 1856807 TI - Detection of circulating endothelial antigen. AB - In order to determine whether endothelial cell antigens are detectable in serum from patients with rheumatic disease characterized by vascular involvement, we developed an ELISA using a monoclonal antibody directed against a 92,000 molecular weight endothelial cell specific antigen designated E92. Sera were assayed from 191 patients and 34 healthy controls. E92 was undetectable or present in very low concentrations in healthy controls and was elevated in most patients with an active rheumatic disease. Our results indicate that circulating endothelial antigens are present in rheumatic vascular syndromes and may provide a measure of endothelial cell function. PMID- 1856808 TI - No conclusive evidence of an epidemiological relation between Klebsiella and ankylosing spondylitis. AB - Fifty-six patients with ankylosing spondylitis and 87 healthy controls were screened for Klebsiella strains in their stools using a new highly sensitive culture medium. The presence of Klebsiella strains in the patient group was compared with activity of the disease. In a dynamic study changes in Klebsiella quantity over a period of 3 months were compared with changes in disease activity over the same period. The patient and control group showed similar percentages of Klebsiella carriage. In the patient group no temporal relation could be found between activity of the disease and the presence of Klebsiella in the intestinal tract. PMID- 1856809 TI - Antinuclear antibody profile in juvenile rheumatoid arthritis. AB - Immunoblot positive sera from children with juvenile rheumatoid arthritis detected from 1 to greater than or equal to 10 proteins in HeLa nuclear sonicates. Thirty percent of the sera reacted with histone H1. Antibodies to at least 1 of 6 most frequently detected nonhistone proteins were present in 85% of the sera. Using immunopurified antibodies to each of the 6 common antigens, we found that 4 of them were associated with mitotic chromosomes. Most sera detected at least 1 of these 4 nonhistone chromosomal proteins. Fifteen percent of the sera immunoprecipitated ribonucleoproteins; some exhibited a novel specificity, precipitating mature transcripts of RNA polymerase III. When present, antibodies to a 45 kDa protein occur only in sera from children without iritis and not in those with active iritis. Overall, the antibody profiles were highly individual and did not appear to correlate with disease subtype or activity. PMID- 1856810 TI - The value of bupivicaine hip injection in the differentiation of coxarthrosis from lower extremity neuropathy. AB - A series of 18 consecutive patients with roentgenographically proven osteoarthrosis (osteoarthritis, OA) of the hip and spine were evaluated because of concomitant lower extremity pain below the knee. To determine whether the leg symptoms were coxalgic or neuropathic, intraarticular hip bupivicaine was injected as a provocative test. This test allowed correct identification of the source of the pain with a sensitivity of 87%, a specificity of 100%, and an efficiency of 88%. This office test also provides significant savings in terms of diagnostic tests and patient discomfort. PMID- 1856811 TI - Hypertrophic repair of canine articular cartilage in osteoarthritis after anterior cruciate ligament transection. AB - Transection of the anterior cruciate ligament in the dog is used frequently to produce a model of osteoarthritis (OA). Although it results in metabolic, biochemical, biomechanical and morphological changes in the articular cartilage of the unstable knee which resemble those in human OA, it rarely results in full thickness cartilage loss. The lack of progression of the cartilage lesions in this model has generally been attributed to stabilization of the joint by osteophytes and capsular fibrosis which develop following transection of the ligament. In our study transection of the anterior cruciate ligament of adult foxhounds and mongrels resulted in a progressive increase in the amount of articular cartilage in the unstable knee. In articular cartilage from the medial femoral condyle of the unstable knee the total amount of proteoglycan, as assessed by hexuronic acid analysis, and, often, the proteoglycan concentration were increased. Furthermore, the rate of proteoglycan synthesis was commonly elevated, in comparison with that from the contralateral knee. Thus, in these animals knee instability did not lead to loss of cartilage but to an active synthetic response by the chondrocytes resulting in hypertrophic cartilage repair which was sustained for up to 64 weeks of observation. PMID- 1856812 TI - Anterior (cranial) cruciate ligament transection in the dog: a bona fide model of osteoarthritis, not merely of cartilage injury and repair. AB - To help elucidate the longterm outcome in the unstable knees of dogs that have undergone anterior cruciate ligament (ACL) transection, conventional radiography, gait analysis and magnetic resonance imaging (MRI) were performed serially on 3 dogs over a 45-month period after ACL transection. Gait analysis showed that vertical forces generated by the cruciate deficient leg were smaller than those produced by the contralateral leg, but the decrease in loading was not progressive and clinical findings did not suggest that the dogs developed pain in the unstable limb. Despite progressive osteophytosis and subchondral sclerosis, as seen on plain radiographs, MRI demonstrated that articular cartilage in the unstable knee was thicker than that in the contralateral knee 36 months after ACL transection. Nine months later, however, striking focal loss of articular cartilage was seen in the unstable knee of each dog. Our study, which provides the first longterm observations of the changes in the unstable knee after ACL transection, shows that they represent progressive osteoarthritis and emphasizes that a prolonged phase of cartilage hypertrophy may precede the stage of cartilage breakdown. PMID- 1856813 TI - Clinical usefulness of amitriptyline in fibromyalgia: the results of 23 N-of-1 randomized controlled trials. AB - Twenty-three double blind, randomized, multiple crossover trials (N-of-1 RCT) of amitriptyline were conducted in patients with fibromyalgia. The benefit of amitriptyline was assessed using a symptom questionnaire and count of tender points. To assess the usefulness of the method, the proportion of trials that provided a definite answer was examined. Completing the trial resulted in reaching a high degree of confidence in the final management decision in 74% of trials. In 35% of trials, results led to discontinuation of the drug which otherwise would have been continued indefinitely. The drug benefit, if present, was evident within first 2 weeks of therapy. We concluded that these results support the feasibility and usefulness of N-of-1 RCT in rheumatology practice. PMID- 1856814 TI - The effects of cyclobenzaprine on sleep physiology and symptoms in patients with fibromyalgia. AB - A double blind, placebo controlled, crossover design study examined overnight sleep physiology, pain, fatigue, and mood symptoms in 12 patients with fibromyalgia treated with cyclobenzaprine. Nine patients completed the study. Patients receiving cyclobenzaprine showed a decrease in evening fatigue (F = 4.7, p less than 0.05) and an increase in total sleep time (F = 4.4, p less than 0.05). Pain, including tender point count and dolorimetry, mood ratings, and alpha non-REM EEG sleep anomaly were unchanged by cyclobenzaprine. PMID- 1856815 TI - Nocardia asteroides infection complicating rheumatoid arthritis. AB - We describe a case of pulmonary nocardiosis in a patient with rheumatoid arthritis (RA) receiving treatment with combined immunosuppressive agents and prednisone. This infection is still considered rare, hard to diagnose, and difficult to treat. To the best of our knowledge, such a case has not been described in a patient with RA. PMID- 1856816 TI - Rheumatoid iliopsoas bursitis presenting as unilateral femoral nerve palsy. AB - A 65-year-old woman with rheumatoid arthritis (RA) developed symptomatic compression of the femoral nerve secondary to an iliopsoas bursitis. Her adjacent hip joint was not severely affected by arthritis. This entity should be included among the entrapment neuropathies complicating RA. PMID- 1856817 TI - Seronegative symmetric polyarthritis in Sezary syndrome. AB - We describe a patient with Sezary syndrome and seronegative symmetric polyarthritis. Detailed analysis of the synovial membrane, including T lymphocyte subset delineation, demonstrated that malignant synovial infiltration was the direct cause of arthritis in this patient. PMID- 1856818 TI - Interstitial lung disease and cryoglobulinemia in polymyositis. AB - Alveolar septal deposits of immunoglobulins and complement were found in the lung biopsy of a patient with polymyositis and interstitial lung disease. Anti-Jo 1 antibody was present in the serum and in isolated mixed cryoglobulins of the patient, suggesting the role of immune complex deposition in the pathogenesis of lung disease. Significant amounts of cryoglobulins were found in 10 of 16 (62.5%) patients with polymyositis/dermatomyositis tested. PMID- 1856819 TI - Giant cell arteritis presenting as limb claudication. Report and review of the literature. AB - Upper limb claudication and pulselessness is an uncommon presentation of giant cell arteritis (GCA), often resulting in delayed diagnosis. We describe such a case diagnosed by angiography, in which a temporal artery biopsy showed classic GCA, despite the absence of local signs or symptoms. A review of 26 similar cases revealed that in 81% of patients where the only manifestation of GCA was upper limb findings, temporal artery biopsy yielded positive findings. Steroid therapy clinically improved 24/26 patients. These findings suggest that a consideration of temporal artery biopsy early in the investigation will hasten diagnosis and appropriate therapy. PMID- 1856820 TI - Pyogenic arthritis caused by Streptococcus milleri in a nonimmunocompromised host. AB - We describe a case of pyogenic arthritis caused by S. milleri (S. anginosus) in a non-immunocompromised host. No other septic focus was found. S. milleri is now widely recognized as an important cause of pyogenic infection, though it eluded suspicion for many years. The rarity of reports of articular infections by S. milleri might be due to problems associated with its recognition. PMID- 1856821 TI - Kaposi's sarcoma in a patient with rheumatoid arthritis possible responsibility of captopril in the development of lesions. AB - Kaposi's sarcoma appeared 8 months after the start of captopril treatment in a 70 year-old woman with rheumatoid arthritis. A marked reduction of cutaneous and gastric lesions occurred when captopril was stopped. These findings are compared to immunosuppressive drug induced forms of Kaposi's sarcoma. PMID- 1856822 TI - Flow cytometry and the rheumatic diseases. PMID- 1856823 TI - Does modified autonomic nervous system activity trigger remission of RA in pregnancy? PMID- 1856824 TI - Prolactin in primary fibromyalgia and rheumatoid arthritis. PMID- 1856825 TI - Erythermalgia in SLE. PMID- 1856826 TI - Treatment of Felty's syndrome with intravenous methotrexate. PMID- 1856827 TI - Borrelia infection as a possible cause of HLA-B27 negative sacroiliitis. PMID- 1856828 TI - Septic arthritis secondary to group C streptococcus typed as Streptococcus equisimilis. PMID- 1856829 TI - Aldolase B mutations in Italian families affected by hereditary fructose intolerance. AB - Hereditary fructose intolerance (HFI) is an inborn error of metabolism caused by aldolase B deficiency. The aldolase B gene has been cloned and the following mutations causing HFI have been identified: A149P (a G----C transversion in exon 5), A174D (a C----A transversion in exon 5), L288 delta C (a base pair deletion in exon 8), and N334K (a G----C transversion in exon 9). We have investigated the occurrence of these mutations in 11 Italian patients affected by HFI using PCR and hybridisation to specific oligomers. We found that four patients were homozygous for the A149P mutation, two patients were homozygous for the A174D mutation, three patients were compound heterozygotes for both the A149P and A174D mutations, one patient was homozygous for the N334K mutation, and one patient did not show any of the reported mutations (HFI diagnosis carried out by aldolase B assay). The L288 delta C mutation has not been found in this survey. PMID- 1856830 TI - Homozygous beta+ thalassaemia owing to a mutation in the cleavage-polyadenylation sequence of the human beta globin gene. AB - A mild, non-transfusion dependent, beta thalassaemia phenotype is described in a Dutch patient homozygous for a mutation in the cleavage-polyadenylation sequence of the beta globin gene. The molecular basis of the mutation, AATAAA greater than AATGAA, was determined using denaturing gradient gel electrophoresis (DGGE) and direct sequencing of genomic DNA amplified by the polymerase chain reaction (PCR). Different fragments of the beta globin gene were amplified and analysed on DGGE for the presence of mutations. The fragment with an abnormal melting behaviour was reamplified and the base substitution in the polyadenylation sequence was identified by direct sequencing. PMID- 1856831 TI - Paternal origin of the chromosomal deletion resulting in Wolf-Hirschhorn syndrome. AB - DNA samples were obtained from children with Wolf-Hirschhorn syndrome and their parents to assist with gene mapping studies of 4p16.3 (the region known to contain the Huntington's disease gene). A panel of seven families was studied, using polymorphic DNA markers, to determine the parental origin of the chromosome abnormality resulting in Wolf-Hirschhorn syndrome. All seven cases were the result of de novo deletions or rearrangements of 4p and in each case the abnormality arose on the paternal chromosome. Analysis of the 3' hypervariable regions of the alpha globin and mucin loci indicated that non-paternity was unlikely to be an explanation for these results. A paternal age effect was not observed. The possibilities of an environmental influence or genetic imprinting require further consideration. This report extends information regarding the preponderance of the paternal origin of de novo structural deletion syndromes. PMID- 1856832 TI - PCR amplification of genomic DNA from a 24 year old lysate derived from washed human erythrocytes. PMID- 1856833 TI - Hereditary multiple exostoses. PMID- 1856834 TI - Neonatal Marfan syndrome with congenital arachnodactyly, flexion contractures, and severe cardiac valve insufficiency. AB - We describe a male neonate with severe arachnodactyly, hypermobility of the fingers, flexion contractures of elbows, wrists, hips, and knees, micrognathia, crumpled ears, rockerbottom feet, loose redundant skin, and ocular abnormalities. Severe cardiac valve insufficiency and aortic dilatation resulted in cardiac failure and death 20 hours after birth. This case represents the severe end of the clinical spectrum of Marfan syndrome. As similar patients have been reported, they may represent a separate mutation. PMID- 1856835 TI - Cardiac rhabdomyomata and megacystis-microcolon-intestinal hypoperistalsis syndrome. AB - Multiple cardiac rhabdomyomata were discovered on necropsy tissue review of a previously well child with megacystis-microcolon-intestinal hypoperistalsis syndrome, who died unexpectedly at home at 40 months of age. Multiple cardiac rhabdomyomata occur rarely and have not previously been reported with this syndrome. They are most frequently associated with tuberous sclerosis. The finding of multiple cardiac rhabdomyomata in this patient suggests the possibility that these two rare conditions may be associated. Putative gene loci for tuberous sclerosis have been assigned to the long arms of chromosomes 9 and 11 and it is possible that the cardiac rhabdomyomata seen in this patient are a serendipitous indicator of the location of the megacystis-microcolon-intestinal hypoperistalsis gene. PMID- 1856836 TI - Short stature, brachydactyly, and Peters' anomaly (Peters'-plus syndrome): confirmation of autosomal recessive inheritance. AB - Two sibs with a phenotype characterised by short stature, brachydactyly, and ocular anomalies (Peters' anomaly) are reported (Peters'-plus syndrome). The consanguinity is in agreement with the proposed autosomal recessive inheritance. PMID- 1856837 TI - Deletion 14q (q22q23) associated with anophthalmia, absent pituitary, and other abnormalities. AB - A fetus is described with anophthalmia, absent pituitary, hypoplastic adrenal glands and kidneys, absent left horn of the uterus, underdeveloped genitalia, and clinodactyly, with a deletion of 14(q22q23). A review of published reports found no similar deletion cases. PMID- 1856838 TI - Schizophrenia and mental retardation in an adult male with a de novo interstitial deletion 9(q32q34.1). AB - A 28 year old man with mental retardation and therapeutically controlled schizophrenia was found to have a de novo interstitial deletion in the long arm of a chromosome 9 (46,XY,del(9)(q32q34.1). Additional phenotypic abnormalities included short stature, a short webbed neck with a low posterior hairline, dysmorphic facies, a narrow palate with an inverted V soft palate, and tapered fingers with bilateral short fifth metacarpals. Interstitial deletion of chromosome 9 is a rare finding and we are aware of only one other case involving the q32q34.1 region. PMID- 1856839 TI - Reproductive fitness and frequency of new mutations in Becker muscular dystrophy: implications for genetic risk estimates. PMID- 1856841 TI - An analysis of women dentists licensed in the State of Michigan: a demographic profile. PMID- 1856840 TI - One person's viewpoint. PMID- 1856842 TI - Women in dentistry--past, present and future. PMID- 1856843 TI - Association organized to recognize women dentists. PMID- 1856844 TI - A dishwasher in every operatory. PMID- 1856845 TI - Ukrainian heritage part of dental practice. Mother-daughter team is unique. PMID- 1856846 TI - Providing health care to those who provide health care for others: directive 90 1. PMID- 1856847 TI - Smoking cessation counseling in the dental office: the time has come. PMID- 1856848 TI - "Don't be six months late for your six month checkup". New dental marketing campaign created for Michigan. PMID- 1856849 TI - Reporting child abuse and neglect: the dentist's responsibility. PMID- 1856850 TI - Want to help fight child abuse? Here's how. PMID- 1856851 TI - We can prevent murder! PMID- 1856852 TI - Education and infection control policy. PMID- 1856853 TI - Guided tissue regeneration: a new frontier in periodontics. PMID- 1856855 TI - Determination of the positions of bound water molecules in the solution structure of reduced human thioredoxin by heteronuclear three-dimensional nuclear magnetic resonance spectroscopy. AB - The presence of bound water molecules in the solution structure of reduced human thioredoxin has been investigated using three-dimensional 1H rotating frame Overhauser 1H-15N multiple quantum coherence spectroscopy. It is demonstrated that the backbone amide protons of Lys21, Lys39, Lys82, Gly83 and Asn102, as well as the side-chain amide group of Asn102, are in close proximity to bound water molecules. Examination of the high-resolution solution structure of reduced human thioredoxin reveals that these results are best accounted for by four bound water molecules. Subsequent simulated annealing calculations carried out on the basis of interproton distance and hydrogen bonding restraints to the bound water molecules, supplemented by the original set of experimental restraints used in the calculation of the three-dimensional structure of human thioredoxin, permit a more precise localization of the bound water positions. Potential hydrogen bonds to these water molecules are described and a comparison is made to corresponding bound water molecules in the crystal structure of oxidized Escherichia coli thioredoxin. PMID- 1856854 TI - Binding of the anticodon domain of tRNA(fMet) to Escherichia coli methionyl-tRNA synthetase. AB - A stem and loop RNA domain carrying the methionine anticodon (CAU) was designed from the tRNA(fMet) sequence and produced in vitro. This domain makes a complex with methionyl-tRNA synthetase (Kd = 38(+/- 5) microM; 25 degrees C, pH 7.6, 7 mM MgCl2). The formation of this complex is dependent on the presence of the cognate CAU anticodon sequence. Recognition of this RNA domain is abolished by a methionyl-tRNA synthetase mutation known to alter the binding of tRNA(Met). PMID- 1856856 TI - Crystallization studies of cAMP-dependent protein kinase. Cocrystals of the catalytic subunit with a 20 amino acid residue peptide inhibitor and MgATP diffract to 3.0 A resolution. AB - Crystallographic studies of the catalytic subunit of cAMP-dependent protein kinase demonstrate that the presence of a 20 amino acid residue peptide inhibitor and MgATP during crystallization yields crystals with a different space group and, more significantly, makes an important difference in the quality of the resulting crystals. Under identical experimental conditions, the kinase crystallizes in a cubic space group P4(1)32 (a = b = c = 169.24 A), when no substrates or inhibitors are present, and in the hexagonal space group P6(1)22 (or P6(5)22) (a = b = 80.16 A, c = 288.07 A, alpha = beta = 90 degrees, gamma = 120 degrees) when a 20-amino acid residue peptide inhibitor and MgATP are present. Moreover, the hexagonal crystal diffracts to a resolution of 3.0 A, while the cubic crystals diffract to a resolution of 4.0 A. PMID- 1856857 TI - Crystallization of a photosensitive nitrile hydratase from Rhodococcus sp. N-771. AB - A photosensitive nitrile hydratase from Rhodococcus sp. N-771 has been crystallized in two different crystal forms in its inactive form. One crystal form belongs to an orthorhombic space group P2(1)2(1)2 with unit cell dimensions of a = 117.4 A, b = 145.7 A and c = 52.1 A, and the other form belongs to a hexagonal space group P6(3)22 with unit cell dimensions of a = 110.2 A and c = 412.1 A. PMID- 1856858 TI - Crystallographic data for H-protein from the glycine decarboxylase complex. AB - The H-protein is the pivotal enzyme of the glycine decarboxylase complex responsible for the oxidation of glycine by mitochondria. It has been extracted and purified from pea leaf mitochondria (Pisum sativum). Its molecular weight, based on the amino acid sequence, is 13.3 kDa and it crystallizes in the space group P3(1)21 (or its enantiomorph P3(2)21) with a = b = 57.14 (3) A, c = 137.11 (11) A. The crystals diffract until at least 3.5 A resolution. PMID- 1856859 TI - Crystallization and preliminary X-ray study of blood coagulation factor IX/factor X-binding protein with anticoagulant activity from Habu snake venom. AB - Crystals of a blood anticoagulant from the venom of the Habu snake, Trimeresurus flavoviridis, have been obtained using ammonium sulfate by the vapor diffusion method. The crystals belong to the orthorhombic space group P2(1)2(1)2 with cell dimensions a = 172 A, b = 86 A, c = 65 A, and diffract to at least 4.0 A resolution. PMID- 1856860 TI - An apparent pause site in the transcription unit of the rabbit alpha-globin gene. AB - Transcription of the rabbit alpha-globin gene begins primarily at the cap site, although some upstream start sites are also observed. Analysis by RNA polymerase run-on assays in nuclei shows that transcription continues at a high level past the polyadenylation site, after which the polymerase density actually increases in a region of about 400 nucleotides, followed by a gradual decline over the 700 nucleotides. These features are also observed in the transcription unit of the rabbit beta-globin gene. The region with the unexpectedly high nascent RNA hybridization signal in the 3' flank contains a conserved sequence, KGCAGCWGGR (K = G or T, W = A or T, R = A or G), followed by an inverted repeat. The inverted repeat (perhaps with the conserved sequence) may be a pause site for RNA polymerase II, thus accounting for the increase in polymerase density. This sequence and inverted repeat are found in the 3' flank of several globin genes and the simian virus 40 (SV40) early genes, as well as in the regions implicated in pausing or termination of transcription of eight different genes. Deletion of the conserved sequence and inverted repeat from the 3' flank of the SV40 early region causes a small increase in the levels of transcription downstream from this site. Replacement with the conserved sequence and inverted repeat from the rabbit alpha-globin gene causes an accumulation of polymerases, supporting the hypothesis that polymerases pause at this site. This proposed pause site may affect the efficiency of termination at some sites further downstream, perhaps by loss of a processivity factor. PMID- 1856861 TI - Escherichia coli sigma 70 and NusA proteins. I. Binding interactions with core RNA polymerase in solution and within the transcription complex. AB - This paper describes the binding interactions of Escherichia coli transcription factors sigma 70 and NusA with core RNA polymerase, both free in solution and as a part of the functional transcription complex. High pressure liquid chromatography gel filtration and fluorescence techniques have been used to monitor the binding of these factors to core polymerase in solution at salt concentrations roughly comparable to the in vivo environment (250 mM-KCl, 50 mM potassium phosphate (pH 7.5]; under these conditions all the interacting species exist separately as protein monomers. We find that sigma 70 and NusA binds competitively to core polymerase with a 1:1 binding stoichiometry in this milieu, and that NusA does not bind to the polymerase holoenzyme. Association constants of approximately 2 x 10(9) and 1 x 10(7) M-1 have been measured for the sigma 70 core polymerase interaction and for the NusA-core polymerase interaction, respectively. These findings are consistent with the original formulation of the NusA-sigma 70 cycle put forward by Greenblatt & Li, and provide the basis for a further (and preliminary) quantitative examination of these same interactions within the transcription complex. We use a number of molecular biological techniques, together with data from the literature, to estimate these binding constants in various phases of the transcription cycle. In keeping with our results in solution, we find that the effective binding affinity of sigma 70 for core polymerase within the "open" promoter-polymerase complex is at least 500 fold greater than that of NusA. As the transcription complex moves from the initiation to the elongation phase these relative binding affinities are reversed; the average association constant of NusA for the core polymerase in the elongation complex remains practically the same as in free solution (approx. 3 x 10(7) M-1), while the affinity of sigma 70 for core polymerase in this complex drops to less than 5 x 10(5) M-1. These results are used to begin to define the basic conformational states and interaction potentials of core polymerase in the various stages of the transcription cycle. PMID- 1856862 TI - Escherichia coli sigma 70 and NusA proteins. II. Physical properties and self association states. AB - In this paper we examine the physical properties and potential for self association of the Escherichia coli transcription factors, sigma 70 and NusA. We show, by a combination of chemical crosslinking, equilibrium and velocity sedimentation, quasi-elastic light scattering, and small-angle X-ray scattering that NusA exists as a monomer at KCl concentrations between 0.01 and 1.5 M, and that sigma 70 exists as a monomer at KCl concentrations between 0.1 and 1.5 M. The shape and hydration characteristics of each of these monomeric proteins are also examined. The results serve as background for the companion paper in which a thermodynamic analysis is made of the interactions of these transcription factor with E. coli core RNA polymerase in solution and as a component of the functional transcription complex. PMID- 1856863 TI - Order-disorder phenomena in myelinated nerve sheaths. III. The structure of myelin in rat optic nerves over the course of myelinogenesis. AB - An X-ray scattering study was performed on optic nerves dissected from rats aged from ten days to one year. The spectra were analysed using the procedure described in the previous papers of this series. Each experiment yields the values of a variety of parameters: the average D and the variance sigma D of the repeat distance, the average number mean value of N of motifs per crystallite, the fraction alpha loose of myelin that does not belong to the compact sheaths, the sets [idiff(h/D)] and [imotif(k/2D)] that suffice to define, respectively, the spurious scattering and the continuous intensity curve of the elementary membrane pair. A surprising result is that, in the native optic, as previously found in the swollen sciatic nerves, the stacking disorder affects the external space, whereas in native sciatic nerves the disorder affects the cytoplasmic space. An analysis of the evolution of the structure parameters as a function of the age of the animal and a comparison with the results previously obtained with rat sciatic nerves led to the following conclusions: the structure of the elementary membrane pair is constant throughout myelinogenesis; mean value of N is much smaller in optic than in sciatic nerves; mean value of N and the degree of myelination increase with age in the two types of nerve; D is smaller in optic than in sciatic nerves; in optic nerves, D decreases slightly with age, but in sciatic nerves it increases; sigma D is strongly age-dependent in optic nerves, but almost age-independent in sciatic nerves. In contrast to sciatic, the structure of optic nerve myelin was found to be almost insensitive to hypertonic solutions. Finally, a pair of electron density profiles was selected, quite similar to those selected previously in sciatic nerves, one corresponding to Caspar & Kirschner's the other to Worthington & McIntosh's proposals, neither of which can be ruled out according to the criteria used in this work. PMID- 1856864 TI - Neutron diffraction study of carbonmonoxymyoglobin. AB - Neutron diffraction data from a crystal of carbonmonoxymyoglobin were refined by PROLSQ, a modern restrained least-squares procedure in reciprocal space, in conjunction with a solvent analysis technique, to a final R-factor of 11.3%. The ligand CO occupies two sites and its binding conformations are distorted from the linear conformation. The N epsilon atom of the distal histidine residue is deprotonated (not deuterated), and a water molecule is bound to the N delta atom of the distal histidine. The side-chain of Lys56 (D6) exists in two alternative charge-binding sites. His24 (B5) and His119 (GH1) share a hydrogen atom. His12 (A10) and His36 (C1) are deprotonated. The deprotonated imidazole ring of His12 (A10) may act as a hydrogen-bond acceptor. The heme group is planar within 0.09 A root-mean-square (r.m.s.) deviation from planarity. The solvent environments for the two propionic acid groups are different. The side-chain of Arg45 (CD3) forms hydrogen bonds with the side-chain of Asp60 (E3) and one of the two propionic acid groups. An average N-2H . . . O angle in helical regions is 147 (+/- 11) degrees. Eleven main-chain amide hydrogen atoms from hydrophobic residues do not exchange with deuterium. The overall atomic occupancy factors for the main-chain and side-chain atoms are quite uniform, at 0.97 (+/- 0.07) and 0.93 (+/- 0.10), respectively, as shown by an occupancy analysis made at the end of the refinement procedure. PMID- 1856865 TI - Lysozyme revisited: crystallographic evidence for distortion of an N acetylmuramic acid residue bound in site D. AB - A structure of the trisaccharide 2-acetamido-2-deoxy-D-muramic acid-beta (1----4) 2-acetamido-2-deoxy-D-glucose-beta (1----4)-2-acetamido-2-deoxy-D-muramic acid (NAM-NAG-NAM), bound to subsites B, C and D in the active-site cleft of hen egg white lysozyme has been determined and refined at 1.5 A resolution. The resulting atomic co-ordinates indicate that the NAM residue in site D is distorted from the full 4C1 chair conformation to one in which the ring atoms C-1, C-2, O-5 and C-5 are approximately coplanar, and the hydroxymethyl group is positioned axially (a conformation best described as a sofa). This finding supports the original proposals that suggested the ground-state conformation of the sugar bound in site D is strained to one that more closely resembles the geometry required for the oxocarbonium-ion transition state, the next step along the reaction pathway. Additionally, detailed analysis at 1.5 A resolution of the environments of the catalytic residues Glu35 and Asp52 provides new information on the properties that may allow lysozyme to promote the stabilization of an unusually long-lived oxocarbonium-ion transition state. Intermolecular interactions between the N acetylmuramic acid residue in site D and the lysozyme molecule that contribute to the saccharide ring distortion include: close packing of the O-3' lactyl group with a hydrogen-bonded "platform" of enzyme residues (Asp52, Asn46, Asn59, Ser50 and Asp48), a close contact between the hydroxymethyl group of ring D and the 2' acetamido group of ring C and a strong hydrogen-bonded interaction between the NH group of Val109 and O-6 of ring D that stabilizes the observed quasi-axial orientation of the -CH2OH group. Additionally, the structure of this complex shows a strong hydrogen bond between the carboxyl group of Glu35 and the beta anomeric hydroxyl group of the NAM residue in site D. The hydrogen-bonded environment of Asp52 in the native enzyme and in the complex coupled with the very unfavorable direction of approach of the potential carboxylate nucleophile makes it most unlikely that there is a covalent glycosylenzyme intermediate on the hydrolysis pathway of hen egg-white lysozyme. PMID- 1856866 TI - X-ray analysis of the single chain B29-A1 peptide-linked insulin molecule. A completely inactive analogue. AB - A crystal structure of a totally inactive insulin molecule has been determined. For this insulin molecule, the first without detectable activity to be characterized, the A and B-chains are linked by a peptide bond between A1 Gly and B29 Lys. The molecule has retained all its normal self-association properties and it can also accommodate the two different conformations designated T and R, as seen in 4Zn native pig insulin crystals. The hexamers of the crosslinked insulin molecule were crystallized using the 4Zn insulin recipe of Schlichtkrull. The structure has been crystallographically refined with data extending to 2 A using restrained least-square methods. Comparison of the B29-A1 peptide crosslink insulin and the 4Zn native insulin reveals close structural similarities with the native dimer. The analysis of the structure confirms the earlier hypothesis that insulin structures in crystals are not in an active conformation and that a separation of N-terminal A-chain and C-terminal B-chain is required for interaction with the insulin receptor. PMID- 1856867 TI - Beta-lactamase of Bacillus licheniformis 749/C. Refinement at 2 A resolution and analysis of hydration. AB - The crystallographic and molecular structure of the class A beta-lactamase (penicillinase) of Bacillus licheniformis 749/C has been refined with X-ray diffraction data to 2 A resolution. For the 27,330 data with F greater than or equal to 3 sigma(F), the R factor is 0.15; for all 30,090 data, R is 0.16. The estimated co-ordinate error is 0.15 A. In the final model, the deviation of covalent bonds and angles from ideality is 0.012 A and 2.2 degrees, respectively. The model includes two molecules of 29,500 daltons each in the asymmetric unit of space group P2(1), 484 water molecules and two tetrahedral buffer anions. Overlay of the two protein molecules results in a root-mean-square difference of 0.17 A and 0.41 A for alpha-carbon atoms and for all atoms, respectively. Twenty-six water molecules fall within 0.25 A of matching water molecules associated with the second protein molecule. The reactive Ser70 is on a turn of 3(10) helix at the N terminus of a longer alpha-helix (72-83). The penicillin-binding site near this helix contains at least seven water molecules. Upon penicillin entry, a water molecule in the oxyanion hole, hydrogen-bonded between the N terminus of helix (80-83) and beta-strand (230-238), would be displaced by the oxygen atom of the beta-lactam carbonyl group. An unexpelled molecule of water is proposed to be the catalytic water required for penicillin hydrolysis. The water is hydrogen bonded to Glu166, a conserved residue in all beta-lactamases, and it lies 3 A from the alpha-face of a previously modeled penicillin. The position of the water Glu166 pair is stabilized in the active site by a cis peptide bond at Pro167. PMID- 1856868 TI - Are time-averaged restraints necessary for nuclear magnetic resonance refinement? A model study for DNA. AB - A recently suggested method for refinement of structural data obtained from two dimensional nuclear magnetic resonance experiments using molecular dynamics (MD) is explored. In this method, the time-averaged values of the appropriate internal co-ordinates of the molecule, calculated from the MD trajectory, are driven by restraints towards the experimental target values. This contrasts with most refinement procedures currently in use, where restraints are applied based on the instantaneous values of the appropriate co-ordinates. Both refinement methods are applied to the EcoRI restriction site DNA hexamer d(GAATTC)2, using target nuclear Overhauser enhancement distances derived from a one nanosecond unrestrained MD simulation of this structure. The resulting refined structures are compared to the results of the unrestrained MD trajectory, which serves as our "experimental" data. We show that although both methods can yield an average structure with the correct gross morphology, the new method allows both a much more realistic picture of inherent flexibility, and reproduces fine conformational detail better, such as sequence dependency. We also analyze the very long MD trajectory generated here (longer than any previously reported for a DNA oligomer), and find that significantly shorter simulations, typical of those frequently performed, may not yield acceptably reliable values for certain structural parameters. PMID- 1856870 TI - Computational method for the design of enzymes with altered substrate specificity. AB - A combination of enzyme kinetics and X-ray crystallographic analysis of site specific mutants has been used to probe the determinants of substrate specificity for the enzyme alpha-lytic protease. We now present a generalized model for understanding the effects of mutagenesis on enzyme substrate specificity. This algorithm uses a library of side-chain rotamers to sample conformation space within the binding site for the enzyme-substrate complex. The free energy of each conformation is evaluated with a standard molecular mechanics force field, modified to include a solvation energy term. This rapid energy calculation based on coarse conformation sampling quite accurately predicts the relative catalytic efficiency of over 40 different alpha-lytic protease-substrate combinations. Unlike other computational approaches, with this method it is feasible to evaluate all possible mutations within the binding site. Using this algorithm, we have successfully designed a protease that is both highly active and selective for a non-natural substrate. These encouraging results indicate that it is possible to design altered enzymes solely on the basis of empirical energy calculations. PMID- 1856869 TI - Structure of bovine prothrombin fragment 1 refined at 2.25 A resolution. AB - The structure of bovine prothrombin fragment 1 has been refined at 2.25 A resolution using high resolution measurements made with the synchrotron beam at CHESS. The synchrotron data were collected photographically by oscillation methods (R-merge = 0.08). These were combined with lower order diffractometer data for refinement purposes. The structure was refined using restrained least squares methods with the program PROLSQ to a crystallographic R-value of 0.175. The structure includes 105 water molecules with occupancies of greater than 0.6. The first 35 residues (Ala1-Leu35) of the N-terminal gamma-carboxy glutamic acid domain (Ala1-Cys48) of fragment 1 are disordered as are two carbohydrate chains of Mr approximately 5000; the latter two combine to render 40% of the structure disordered. The folding of the kringle of fragment 1 is related to the close intramolecular contact between the inner loop disulfide groups. Half of the conserved sequence of the kringle forms an inner core surrounding these disulfide groups. The remainder of the sequence conservation is associated with the many turns of the main chain. The Pro95 residue of the kringle has a cis conformation and Tyr74 is ordered in fragment 1, although nuclear magnetic resonance studies indicate that the comparable residue of plasminogen kringle 4 has two positions. Surface accessibility calculations indicate that none of the disulfide groups of fragment 1 is accessible to solvent. PMID- 1856871 TI - Molecular recognition. Conformational analysis of limited proteolytic sites and serine proteinase protein inhibitors. AB - The conformations of known tryptic limited proteolytic sites have been analysed and compared to the structures of the binding regions of serine proteinase inhibitors, as they are found when complexed to a serine proteinase. Conformational parameters studied include main-chain torsion angles, root-mean square fits, accessibility, mobility and protrusion indices. As observed before, the inhibitors share a common main-chain conformation at the binding loop from P3 P'3 (Schechter & Berger notation), which is maintained throughout all the serine proteinase inhibitor families for which X-ray data is available, despite lack of similarity in the rest of the protein. This canonical structure is not found amongst the limited proteolytic sites (or nicksites), which differ markedly from the inhibitor binding loop conformation, and also amongst themselves. The experimentally determined nicksites are in general both accessible and protruding; as are the inhibitor binding loops, as well as being typically flexible regions of structure, as denoted by elevated temperature factors from crystallographic determinations. For cleavage by serine proteinases these loops must radically alter their local conformations and a large motion of the loop relative to the structure, in some cases, would be required to orientate these sites for cleavage. PMID- 1856874 TI - Abstracts of the annual meeting (North American Section) of the International Society for Heart Research. Cincinnati, Ohio, 29 May-2 June 1991. PMID- 1856872 TI - Relation between stability, dynamics and enzyme activity in 3-phosphoglycerate kinases from yeast and Thermus thermophilus. AB - 3-Phosphoglycerate kinases from yeast and the extreme thermophilic bacterium Thermus thermophilus HB8 have been used as models for investigating the relationship between stability, dynamics and activity. It was found that while at a given temperature the thermophilic protein is more stable, its conformational dynamics as measured by the ability of acrylamide to quench the fluorescence of a buried tryptophan as well as its specific activity, are both lower than for the mesophilic protein. As the temperature is increased, the thermodynamic stability of the thermophilic protein approaches that of the mesophilic protein at its working temperature. Its conformational dynamics and specific activity however were both shown to increase, until at the physiologically operational temperature, they become similar to those of the mesophilic enzyme at its operational temperature. These results confirm the proposal that a direct relationship and balance holds between thermodynamic stability, dynamics and specific activity in globular proteins. They demonstrate also the constraining effect of increased stability upon conformational dynamics and enzyme activity. PMID- 1856875 TI - Neurotoxicities and behavioral changes in a 12-year-old male exposed to dicofol, an organochloride pesticide. AB - The case of a 12-yr-old male exposed to a substantial amount of dicofol, a DDT analog, is presented. The patient was still contaminated 3 wk after exposure. Blood and fat analysis documented the presence of dicofol. The patient demonstrated subjective and objective evidence of neurological injury, which resolved. Other organ injury was not present. Cognitive and emotional difficulties persisted over an 18-mo period. PMID- 1856873 TI - In vivo strain in cranial sutures: the zygomatic arch. AB - Although cranial sutures presumably play a role in absorbing and/or transmitting loads applied to the skull, loading patterns on facial sutures are poorly understood. The zygomatic arch provides a comparatively isolated mechanical part of the skull containing a single suture, the zygomatico-squamosal. In pigs the zygomatico-squamosal suture has a short vertical segment located within the postorbital process and a longer horizontal segment which extends posteriorly. In anesthetized pigs single-element high-elongation strain gages were bonded over both segments of the suture. Strain was recorded during stimulation of the masseter muscles and while the lightly anesthetized animals masticated food pellets. The predominant strain patterns differed in the two segments of the suture. During mastication compressive strains predominated in the vertical segment, but tensile strains predominated in the horizontal segment. The same patterns were also produced by stimulation of the ipsilateral masseter muscle. Contraction of the contralateral masseter reversed the strain pattern, but strain levels were low and during mastication such reversals occurred only transiently. The two segments of the suture have contrasting morphologies. The vertical segment has broad, interdigitating contacts with fibers arranged in a compression resisting orientation. The horizontal segment has a simple tongue and groove structure with fibers arranged to resist tension. Thus, the structure of the suture reflects the predominant strain pattern. PMID- 1856876 TI - Correlation of cadmium, copper, manganese, and zinc levels in the urine of people in nonpolluted areas. AB - Quantitative correlation among the four metals cadmium, copper, manganese, and zinc was examined in nearly 1500 urine samples collected from adult female inhabitants in 8 nonpolluted regions in various parts of Japan. In addition to a significant correlation between urinary cadmium and zinc as previously reported, copper levels significantly correlated with those of cadmium and zinc. In contrast, manganese did not show any significant correlation with cadmium, copper, or zinc. These findings are in agreement with the fact that cadmium, copper, and zinc are known to combine with metallothionein in vivo, whereas this is not the case with manganese. PMID- 1856877 TI - Diversity of shellfish toxins of "diarrhetic" type revealed by biological and chemical assays. AB - Extracts of "diarrhetic" shellfish toxins from the edible mussel (Mytilus edulis) were tested with biological and chemical assays to determine toxin content. When tested with the standard mouse bioassay, a higher toxicity was detected in most samples compared to that revealed from detection of the diarrhea-causing substances okadaic acid and dinophysistoxin-1 by high-performance liquid chromatography. Routine extraction of toxins for the two assays was carried out with two different solvents, acetone versus aqueous methanol. Accordingly, we questioned whether the variation in results between the methods could be due to differences in chemical properties of these two solvents. When tested, the two solvent systems showed practically the same efficiency concerning the extraction of okadaic acid and dinophysistoxin-1. This demonstrated that toxins other than those causing diarrhea were present in the samples, and that the mouse bioassay was sensitive to these additional toxins. Subsequent testing of the samples with the mouse bioassay, employing both acetone and methanol extracts, revealed that at least two classes of toxins were present in the mussel samples in addition to okadaic acid and dinophysistoxin-1. It is unclear whether the shellfish toxins revealed in this study are partially from known, nondiarrhetic types, such as pectenotoxins or yessotoxins, or from unknown toxin groups exhibiting ichthyotoxic and hemolytic properties. PMID- 1856878 TI - Subchronic inhalation toxicity and reproductive assessment in rats of three chlorinated propenes. AB - Groups of 15 male and 15 female Sprague-Dawley rats were exposed to 1 of 3 chloropropene (2,3-Di = DCP; 1,2,3-Tri = TRCP; and 1,1,2,3-Tetra = TECP) vapors to provide information on repeated exposures and the potential for reproductive impairment by the most likely route of occupational exposure. Target exposure concentrations were 0, 1, 5, and 15 ppm, 6 h/d, 5 d/wk for 13 wk. The following parameters were evaluated: pharmacotoxic signs, survival, body weights, hematology, clinical blood chemistry, urine analysis, gross and histopathology (over 40 tissues/rat), organ weights, and selected weight ratios. Signs of nasal irritation were noted in rats exposed to 15 ppm of either DCP or TRCP but not TECP. Small decreases in overall body weight were observed in female rats exposed to 15 ppm TCP. An increase (approximately 15%) in spleen weight, with no corresponding histopathological or clinical findings, was observed in 15 ppm DCP treated male rats. No other effects considered related to treatment were observed following exposure to any of the three chlorinated propenes. Additional groups of 10 male and 20 female Sprague-Dawley rats were exposed to DCP, TRCP, or TECP vapors at target concentrations of 0, 1, or 5 ppm for 6 h/d, 5 d/wk for a 10-wk premating period, a mating period, and the first 14 d (females only) of gestation. Females were allowed to deliver litters and the offspring were evaluated during a 21-d lactation period. Mating, pregnancy, and fertility indices were generally comparable among all test groups, although female mating and pregnancy indices of both DCP-treated females were lower than expected in the regular and postrecovery reproduction phase. No effects were seen on pup survival, sex distribution, body weights, organ weights, and ratios. A modest reduction in pup body weights was observed following TECP exposure but was attributed to large litter size. No treatment-related effects were seen following necropsy of adults or weanlings, nor were such effects noted following microscopic evaluation of gonads from parental animals. PMID- 1856879 TI - Short-term dermal toxicity and mutagenicity of coal coprocessing products in the rat. AB - The present study was conducted to determine the dermal toxicity of coal coprocessing products and to assess their potential health hazards. Groups of 10 male and 10 female Sprague-Dawley rats were administered dermally coal coprocessing products (light gas oil, LGO; heavy gas oil I, HGOI; heavy gas oil II, HGOII) at 1 g/kg body weight/d for 14 d. The control and positive control groups received normal saline and a coal liquefaction product (CLP) at the same dose level, respectively. Treatment with either the three fractions of coprocessing products or CLP caused decreased growth rate and food consumption in animals of both sexes. Liver enlargement occurred in groups treated with HGOI, HGOII, and CLP. Decreased serum glucose was observed in animals of both sexes treated with the three fractions and CLP. Treatment with HGOI and CLP caused an elevation of hepatic microsomal ethoxyresorufin deethylase activity in the rat of both sexes. The three fractions and CLP caused mild anemia. Mild treatment related histological changes were observed in the liver, spleen, thyroid, bone marrow, and kidney. All three fractions of coprocessing products were tested for their mutagenicity in five strains of Salmonella typhimurium: TA98, TA100, TA1535, TA1537, and TA1538. HGOI, after metabolic activation, was found to be mutagenic in the strains of TA98, TA100, and TA1538. In contrast, HGOII was mutagenic in the five strains with or without metabolic activation. These data indicate that HGOI and HGOII are more toxic than LGO, and should be subjected to further studies to determine their long-term effects. PMID- 1856880 TI - Bladder and liver tumorigenesis induced by 2-acetylaminofluorene in different F1 mouse hybrids: variation within genotypes and effects of using more than one genotype on risk assessment. AB - Several F1 mouse hybrids were used in a chronic bioassay to determine whether such an experimental design would provide greater statistical power than using only the B6C3F1 hybrid. For this purpose, the dose response of formation of hepatocellular and bladder tumors after 30 mo of feeding 2-acetylaminofluorene (2 AAF) in the diet was assessed in 4 F1 mouse hybrids, including the B6C3F1 hybrid. No strain background-related differences in frequency of bladder neoplasms between any F1 hybrids were detected. Bladder tumors occurred only at the highest 2-AAF dose in female mice. In males the lowest dose was already sufficient to induce bladder neoplasms with incidences of 25-48% adjusted for different nontumor mortality patterns across doses. No marked strain-related differences in hepatocellular tumor rates were apparent in either sex. Higher frequencies of hepatocellular neoplasms were observed among the untreated control males of the B6C3, AY, and CVA F1 hybrids than among the comparable females. Among treated mice, the lowest 2-AAF dose increased liver tumor incidence, more so among the females than among the males. The different background genomes resulted in somewhat different risk assessments for liver tumor formation in males due to differences in the time-to-tumor curves. Except for the much higher background liver tumor rate in the CVY mice, the adjusted liver tumor incidences were similar across the four hybrids. Hence, the levels of statistical significance obtained for dose-response trends and comparisons of treated and control groups were similar using 48 animals per dose groups with B6C3 mice, or combinations of 24 animals per dose from 2 genotypes, or 12 animals per dose from the 4 hybrid genotypes. Estimates of carcinogenic potency for bladder tumors were similar, within a factor of two, across the four hybrids. However, estimates of liver tumor potency across genotypes varied by a factor of two and six for females and males, respectively. Thus, the mean of cancer potency estimates across these genotypes would be more representative for mice than results from any single genotype. As in chronic carcinogenesis studies with other test agents, neoplasms developed in only a certain proportion, rather than in all, of the genetically identical animals exposed to a given dose of the toxicant for the same length of time under the same controlled environmental conditions. This phenotypic variability in toxic responses may reflect differential regulation of gene expression among the genetically identical test animals. PMID- 1856881 TI - Influence of innervation on molecular forms of acetylcholinesterase in regenerating fast and slow skeletal muscles. AB - Nerve-intact muscle regenerates were prepared by ischemic-toxic injury of slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles of the rat. Rapid innervation of regenerating myotubes modified intrinsic patterns of AChE molecular forms, revealed by velocity sedimentation in linear sucrose gradients. Regarding their onset, the effects of innervation can be classified as early and late. The earliest changes in the SOL regenerates appeared a few days after innervation by their motoneurons: the activity of the 13 S AChE form (A 8) increased significantly in comparison to non-innervated regenerates. The pattern of AChE molecular forms became similar to that in the normal SOL muscle during the 2nd week after injury. In contrast, no major differences were observed between 8 day-old innervated and non-innervated EDL regenerates. Their patterns of AChE molecular forms resembled that in the normal EDL. However, the predominance of the 10 S AChE form (G 4) characteristic for the 2-week old non innervated regenerates was prevented by innervation. Early effect of innervation observed in the SOL regenerates but not in the EDL may be due to intrinsically different response of the regenerating SOL myotubes to innervation. Rather high extrajunctional activity of the asymmetric 16 S (A 12) molecular form of AChE in early regenerates was reduced to adult level in about 3 weeks in the SOL, and nearly completely suppressed in 5 weeks after innervation in the EDL regenerates. This reduction is assumed to be a late effect of innervation, as well as a decrease of the activity of the 4 S AChE form (G 1) in the SOL regenerates. A suppressive mechanism is activated in the extra-junctional regions of the innervated muscle regenerates during their maturation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856883 TI - Endogenous opioid-immunoreactive neurons of the ventromedial hypothalamic nucleus concentrate estrogen in male and female rats. AB - Estrogen stimulates expression of proenkephalin mRNA in neurons of the hypothalamic ventromedial nucleus, and evidence is accumulating that synaptic release of one of the peptide end products, met-enkephalin, influences events that regulate reproductive behavior. To address the question of whether estrogen acts directly on neurons that synthesize met-enkephalin or indirectly through a separate neuronal population, we combined estrogen autoradiography with endogenous opioid peptide (EOP) immunohistochemistry. In agreement with previous studies, the ventrolateral subdivision of the hypothalamic ventromedial nucleus was densely packed with EOP-immunoreactive cells. In males, 48% of the estrogen concentrating cells of the ventrolateral subdivision of the hypothalamic ventromedial nucleus contained EOP, and, in females, 27% of the estrogen concentrating cells contained EOP. These findings indicate that estrogen acts directly on neurons that express EOP and suggest a mechanism that underlies sexually differentiated reproductive behavior. PMID- 1856882 TI - Regulation of heat shock protein synthesis in rat astrocytes. AB - Rat forebrain astrocytes synthesize heat shock proteins with molecular weights 97, 89, 70, 68, and 30-34 kilodaltons. The stress inducible 68-kDa heat shock protein (HSP-68) was vigorously expressed by astrocytes in culture after a 45 degrees C, 20 min heat shock. HSP-68 synthesis was poorly inducible by a second heat shock given 16 hr after the initial heat shock. Decreased [35S]methionine incorporation into HSP-68 correlated with low levels of HSP-68 mRNA present after the second heat shock. The data suggest that control of HSP-68 mRNA levels by transcriptional/posttranscriptional mechanisms is a major site for regulation of HSP-68 synthesis. PMID- 1856884 TI - Role of nucleus basalis in cholinergic control of cortical blood flow. AB - The present investigation was designed to determine the effect of lesions localized to the nucleus basalis/substantia innominata (NB) on resting and cholinergically activated regional cerebral cortical blood flow (rCBF). Ibotenic acid (10 micrograms) was infused locally at 1 mm caudal to bregma, 3 mm lateral to the midline, and 8 mm below the cortical surface. Effectiveness of lesions was demonstrated by histological verification of lesion sites and determination of choline acetyltransferase activity in cerebral cortex homogenates. rCBF was measured with the autoradiographic iodo-14C-antipyrine technique. Resting rCBF was similar in the hemisphere that received the NB lesion and in the contralateral (intact) side in all regions examined. Physostigmine intravenous infusion (3.3 micrograms.kg-1.min-1) enhanced rCBF in frontal, parietal, occipital, and temporal cortex. The increase was symmetrical, however, indicating inability of NB lesion to affect this phenomenon. It is concluded that the cortical cholinergic afferents originating in the NB are not involved in the control of rCBF. PMID- 1856885 TI - Proliferation of chick embryo neuroblasts grown in the presence of horse serum requires exogenous transferrin. AB - We have previously shown that neuroblasts from cerebral hemispheres of 6-day-old chick embryos are able to proliferate when grown in the presence of fetal calf serum. We report here that in the presence of horse serum alone the proliferative rate of neuroblasts is strongly reduced. A high proliferative rate is restored upon the addition of bovine transferrin and to a lesser extent with added FeSO4 or hemin. These findings suggest that the transferrin of horse serum cannot be used by chick neuroblasts in vitro, while bovine transferrin exogenously added is active in promoting cell proliferation. We propose that the stimulatory activity of the fetal calf serum is due to bovine transferrin, since when this serum is fractionated by gel filtration, the fractions that stimulate the proliferation of neuroblasts grown in the presence of horse serum are located in the molecular weight area of transferrin, and they do contain transferrin as seen by immunoblotting with a specific anti-transferrin antibody. PMID- 1856886 TI - Cerebrospinal fluid catecholamine metabolites in HIV-infected patients. AB - Twenty-eight HIV-seropositive individuals--11 asymptomatic cases, 8 with lymphadenopathy syndrome (LAS), and 9 with AIDS--were investigated. Clinical staging of the AIDS dementia complex was done in the 9 AIDS patients. The catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) in CSF were determined in all the HIV patients and in 20 healthy volunteers. The CSF MHPG levels did not differ significantly between healthy subjects and HIV-infected patients at any stage of the infection. The CSF concentrations of HVA differed between the groups only during the AIDS stage. The mean CSF HVA value in the AIDS patients was 42% lower than in the healthy subjects and significantly lower than in any other stage of HIV infection (P less than .01). Patients with signs of the AIDS dementia complex had reduced CSF HVA levels, but there was no clear relationship between HVA concentration and stage of the AIDS dementia complex. PMID- 1856888 TI - [Comparison of nasal mucociliary clearance before and after operation in chronic sinusitis]. AB - Nasal mucociliary clearance is a first line of defence mechanism of the respiratory system against inhaled particles. It transports particles depositing into the nasal passages to the pharynx to be swallowed or expectorated, thus protecting the respiratory system from injury. Clearance function is affected by many factors such as the chronic inflammation of the paranasal sinuses. A group of 13 healthy volunteers (controls) and a group of 17 patients suffering from chronic sinusitis was investigated in the Department of Otolaryngology of Taichung Veterans General Hospital between June and October of 1990. A radioisotope method was used to measure the velocity of nasal mucociliary transport in the participants. This involved the use of radioisotope Tc99m combined with albumin particles and measurements were made in one nasal chamber at a time. The sinusitis patients were then surgically treated and they all improved. In all 25 tests were made in the control group and the mean velocity of their mucociliary transport was found to be 4.56mm/min. In the patients 28 measurements were made and their mean velocity was found to be 2. 67mm/min before the operation and 4.03mm/min after the operation. The difference between pre- and post-operative velocities was statistically significant as was the difference between the pre-operative velocities of the patients and those of the controls. The difference between controls and patients after the operation was not significant. PMID- 1856887 TI - Study of myopathy in chronic alcoholics with neurological complication. AB - This study was undertaken to understand the myopathic manifestations as well as the electrophysiological, pathological, and histochemical changes in muscle tissues of chronic alcoholics. Twenty eight cases of chronic alcoholics with neurological complications and confirmed myopathy were included in this study. Of these, 11 cases (39.3%) belonged to the subclinical forms with either Korsakoff Wernicke encephalopathy or cerebellar atrophy. The remaining 17 cases (60.7%) were clinical forms with various manifestations, such as hypokalemic periodic paralysis, alcoholic rhabdomyolysis, vacuolar myopathy with phosphorylase deficiency, chronic proximal limb-girdle myopathy and neuro-myopathy. Electromyography (EMG) study showed both myopathic and neurogenic changes. The single fiber EMG revealed increased jitter and blocking rate suggesting reinnervation. In muscle biopsy, the histological and histochemical abnormalities included random atrophic fibers, necrotic fibers, fibers with internal nuclei, phagocytosis and moth-eaten fibers. There was selective atrophy of type 2 muscle fibers, particularly of type 2B fiber. Total or partial myophosphorylase deficiency was observed in some cases (33%). All these findings indicate typical myopathic changes, which might be caused by defects in the energy pathways, especially in the glycolytic processes. In some muscle specimens, there were angular atrophic fibers and fiber type groupings suggesting denervation and reinnervation changes. In conclusion, both myopathic and neurogenic alterations were frequently observed in muscles of chronic alcoholics. PMID- 1856890 TI - [The study of Apgar score and infant birth weight in the central Taiwan]. AB - The objective of this study was to assess the relationship between birth weight and the Apgar Score. We collected data on the birth weights and the 1 min and 5 min Apgar Score of new born infants between 1982 and 1987 at a teaching hospital in Central Taiwan. Compared to babies with normal Apgar Score, infants with low Apgar Scores were found to born with low and very low birth weights. In the 1 min of life test, the relative risks of low birth weights among infants with Apgar Scores of 0 to 3 and 4 to 6 were 115.0 and 5.9 times higher than those of normal infants, respectively. In the very low birth weight category, the relative risks of the above score were 252.5 and 51.1, in this order. In the 5 min of life test, the relative risks of the above scores were 16.2 and 12.1 in the low birth weight category, respectively. However, among babies of very low birth weight, the relative risks of the same scores were 121.2 and 84.9, in this order. In conclusion, the 5 min Apgar Score might be a useful prognostic index for the relationship between health and birth weight of new born infants. PMID- 1856889 TI - Transmission of hepatitis B virus infection by iatrogenic intramuscular injections in an endemic area. AB - The authors followed 95 people from the general and aboriginal population of Taiwan, aged 5 to 69 years for two years. All of subjects studied were susceptible to hepatitis B virus (HBV) infection. In all, 56 of the 95 persons received iatrogenic intramuscular (IM) injections, and 28 of the 95 became newly infected with HBV during the study period. The relative risk of being infected with HBV was higher in people who received an IM injection (IRR = 5.8, 95% CI 1.9 17.9) than in those who did not. New HBV infections were found to correlate significantly with the frequency of injections (Ptrend less than 0.000) and therefore, we concluded that (A) intramuscular injections played an important role in horizontal transmission of HBV, particularly among Aborigines and that (B) the infection was transmitted via inadequately sterilized syringes used for iatrogenic IM injections in a community in which the hepatitis B virus was prevalent and IM injections were common. PMID- 1856891 TI - Arthrographic evaluation of the internal derangement of temporomandibular joint. AB - From a functional point of view, the temporomandibular joint(TMJ) is one of the most important joints in the body. Optimal radiographic visualization is becoming increasingly important to medical and dental specialists as abnormal TMJ derangements are becoming better understood. Because the most common TMJ arthropathy is the internal derangement of TMJ, arthrography of the temporomandibular joint is widely performed in clinical practice. From January 1986 to December 1990, twenty temporomandibular joint arthrographies were performed in patients with symptoms of pain, clicking and dysfunction. We report our findings on these twenty patients who were examined by arthrography, which was conducted due to internal derangements related to meniscal dysfunction. PMID- 1856892 TI - Experiences in the management of cerebellopontine angle tumour: an analysis of 64 cases. AB - The surgical aspects of 64 consecutive cases of cerebellopontine angle tumours treated from January 1983 to December 1988 are reviewed. Nearly all of the procedures were done through a small suboccipital craniectomy. Two patients underwent a combined subtemporal- suboccipital approach. A stage-operation was performed on three patients harbouring a large to giant-size acoustic neuroma. The most common sign was loss of corneal reflex (29%). Hearing loss was present in 33 patients (51%). Trigeminal neuralgia occurred in 13 patients (20%) on the affected side. Hemifacial spasm was present in one patient with a 2-cm meningioma. The tumour pathology comprised of 37 acoustic neuromas, 16 meningiomas, 5 epidermoid cysts, 3 trigeminal neuromas, 1 metastatic adenocarcinoma, 1 facial neuroma, and 1 tuberculoma. Anatomic continuity of the facial nerve was preserved in 40 patients (66%). Operative mortality rate in this series was three (4.7%). None of the patients has had other further significant neurological deficits postoperatively. Most of our patients were in good condition after the operative procedures. PMID- 1856893 TI - [Compressive radial nerve palsy induced by military shooting training--a case report]. AB - A newly recruited soldier suffered a sudden onset of wrist-drop of left hand and numbness on the back of thumb after a military training course in target shooting. An examination disclosed decreased muscle power (0/5) in the left wrist dorsiflexion, disturbance of pain-temperature sensation on the radial side of left hand and absence of the deep tendon reflex of brachioradialis. Electrophysiological studies showed slowness of motor conduction velocity, delay of distal latency and reduced amplitude. EMG revealed fibrillation over the extensor digitorium communis (EDC) at rest, brachioradialis and prolongation of polyphasic MUAPs over EDC. Left radial nerve mononeuropathy induced by mechanical compression of the radial nerve on the spiral groove of humerus was conspicuous. We attempted to discuss the disease etiology, electrophysiological findings and treatment. PMID- 1856894 TI - [Versatility of rectus abdominis muscle or myocutaneous flap--report of seven cases]. AB - The rectus abdominis muscle, due to its strategic location in the abdomen with its dual blood supply and wide arc of transposition, is ideally suited to repair defects over the chest, abdomen, groin and perineum. The muscle is generally based on the superior epigastric artery, deep inferior epigastric artery and their associated capillary communications. From September 1989 to September 1990, at Taichung Veterans General Hospital, seven cases were presented utilizing unilateral rectus abdominis muscle or myocutaneous flap for local or free tissue transfer. The recipient areas included abdomen, groin, perineum, lower leg and a penis reconstruction. Of all flaps that survived, one developed minor skin necrosis causing urethral orifice stricture and urethrocutaneous fistula that later required repair. All cases achieved the surgical goals. There was no donor site infection, nor abdominal wall herniation but persisted wound pain in 2 cases was noted during the follow-up period. All patients resumed daily activity without limitation about six weeks postoperatively. The large skin territory with abundant soft tissue offers versatile flap design. The dissection is simple, speedy and straight foreward. The deep inferior epigastric vessels are long and their calibers are suitable for vascular anastomosis. Usually, the donor sites are primary closed. We recommend this flap as one to be considered in reconstruction planning and as a donor material for free tissue transfer. PMID- 1856895 TI - Congenital tracheobronchomegaly (Mounier-Kuhn syndrome): a report of 10 cases and review of the literature. AB - Mounier-Kuhn syndrome is a congenital abnormality of the trachea and main bronchi characterized by atrophy or absence of elastic fibers and thinning of muscle, which allows the trachea and main bronchi to become flaccid and markedly dilated on inspiration with narrowing or collapse on expiration or cough. The abnormal airway dynamics and pooling of secretions in broad outpouchings of redundant musculomembranous tissue between the cartilaginous rings predispose to the development of chronic pulmonary suppuration, bronchiectasis, emphysema, and pulmonary fibrosis. A broad spectrum of clinical abnormalities has been documented in Mounier-Kuhn syndrome, ranging from minimal disease with good preservation of pulmonary function to progressive disease leading to respiratory failure and death. In the appropriate clinical setting, Mounier-Kuhn syndrome is diagnosed in women from chest radiographs when the transverse and sagittal diameters of the trachea exceed 21 mm and 23 mm, respectively, and when the transverse diameters of the right and left main bronchi exceed 19.8 mm and 17.4 mm, respectively. In men it is diagnosed when the transverse and sagittal diameters of the trachea exceed 25 mm and 27 mm, respectively, and when the transverse diameters of the right and left main bronchi exceed 21.1 mm and 18.4 mm, respectively. The diagnosis can be confirmed easily by computed tomography. PMID- 1856896 TI - Case report: computed tomography findings in Williams-Campbell syndrome. AB - Williams-Campbell syndrome is a rare type of cystic bronchiectasis that is due to defective cartilage of fourth-to sixth-order bronchi. The diagnosis has been made either at autopsy or by bronchographic findings. The article describes an adult case of this syndrome with CT findings that are characteristic of this entity. CT showed areas of emphysematous lung parenchyma distal to the dilated bronchi, suggesting bronchiolitis obliterans secondary to proximal cystic bronchiectasis. These findings are useful in differentiating Williams-Campbell syndrome from other causes of cystic bronchiectasis, thus obviating bronchography. PMID- 1856897 TI - A prospective evaluation of plain radiographic signs of chronic obstructive pulmonary disease. AB - Plain film signs of COPD, spirometric evidence of airflow obstruction, and smoking history were correlated in a group of 182 men aged 32 to 85 years (average, 57.5 years) who presented for evaluation of possible pulmonary disability. There were 148 current or past smokers (range, 0.66 to 150 pack years; average, 31.89 pack-years) and 34 lifetime nonsmokers. A single observer, who had no knowledge of the other parameters, prospectively evaluated posteroanterior chest radiographs for 11 signs of COPD. Airflow obstruction was defined as a reduction in FEV1/FVC% below the 95% confidence limit of normal. Obstruction was classified on the basis of the reduction in FEV1 as mild (FEV1 greater than 2.5L), moderate (FEV1 greater than 1.0 L and less than 2.5 L), or severe (FEV1 less than 1.0 L). Spirometric evidence of airflow obstruction was present in 67 patients; obstruction was mild in 26, moderate in 36, and severe in 5. We found a statistically significant association between smoking and airflow obstruction on spirometry (P less than 0.001) and an equally significant association between smoking and radiographic signs of COPD on plain chest films (P less than 0.001). Both airflow obstruction and radiologic signs of COPD were generally absent in lifetime nonsmokers. The plain film signs of COPD were only of moderate value in predicting spirometric evidence of airflow obstruction in smokers; spirometric evidence is not the gold standard for the presence of COPD, however, and the strong association between smoking and these radiologic signs may indicate that in smokers the presence of plain film signs of COPD reflects morphologic abnormality in the lungs indicative of disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1856898 TI - Differentiation of bronchogenic carcinoma from postobstructive pneumonitis by magnetic resonance imaging: histopathologic correlation. AB - Obstructive pneumonitis frequently occurs distal to hilar bronchogenic carcinomas or in lung adjacent to peripheral tumors. The article evaluates the role of MRI in the differentiation of tumor from pneumonitis. Twelve patients underwent MRI of the thorax before surgery. T1-weighted (SE 310/20) and T2-weighted (SE 2000/60 120) images were obtained through the tumor and presumed areas of pneumonitis. Five histologic types of pneumonitis were identified on pathologic examination of the 12 specimens. Cholesterol pneumonitis, found in 7 patients, was the most common type. Organizing pneumonitis, bronchiectasis with mucus plugs, atelectasis, and abscess were found in 3, 4, 2, and 1 patients, respectively. MRI was able to differentiate tumor from pneumonitis in 5 of 6 patients with a hilar mass and in 5 of 6 patients with a peripheral tumor. This was achieved by a visual difference in signal intensity on heavily T2-weighted (SE 2000/120) images. Cholesterol pneumonitis and bronchiectasis with mucus plugs were always hyperintense relative to tumor, and organizing pneumonitis and atelectasis were isointense and indistinguishable from tumor. MRI can differentiate tumor from pneumonitis provided that pneumonitis is of the cholesterol type or if there are mucus plugs in the collapsed lung. PMID- 1856899 TI - Differentiation of central lung tumor from postobstructive lobar collapse by rapid sequence computed tomography. AB - When central lung tumor is associated with lobar collapse, discrimination of tumor from atelectasis is important for determining operability or for field planning should radiation therapy be utilized. Because tumor and collapsed lung have similar attenuation values, they cannot always be distinguished with usual contrast-enhanced CT. The article describes separation of tumor from collapsed lung by means of RSCT with bolus injection of nonionic contrast medium. With this technique collapsed lung is appreciably enhanced, but tumor enhancement is slow and minimal. The difference is most marked from 40 seconds to 2 minutes after scanning begins. This phenomenon is probably related to the marked increase in blood flow per unit area of collapsed lung due to crowding of relatively large pulmonary arteries compared to tumor blood supply through small bronchial arteries. Tumor can also be delineated from atelectasis by differences in internal structure with this technique. PMID- 1856900 TI - Computed tomography distinction of central thoracic masses. AB - In an analysis of 36 central lung, 54 mediastinal, and 10 central pleural masses, features were sought that would allow accurate localization of the mass by CT. The mass-lung interface was the most useful feature; with few exceptions a mass with a spiculated, nodular, or irregular edge was in the lung, and a mass with a smooth edge was in the mediastinum. In the superior mediastinal, supraazygos, and supraaortic regions lung masses were lateral to the great vessels, and mediastinal masses were medial to the great vessels. Anterior mediastinal masses were typically positioned between the sternum and great vessels; some were more laterally positioned, however, and could only be distinguished from lung masses by the mass-lung interface. In the infraazygos, infraaortic, and paraspinal areas, lung and mediastinal masses were best differentiated by the mass-lung interface. The angles formed between the mass and lung were occasionally helpful in localizing the mass. Central pleural masses were characterized by a lack of intimate mediastinal effect, obtuse angles between the mass and lung, a smooth mass-lung interface, and characteristic association with other similar areas of involvement in the pleural space. These criteria were used for the correct localization of 99 of 100 masses; therefore, they can simplify and focus the work up of most central thoracic masses. PMID- 1856901 TI - Bronchogenic cyst: a case report emphasizing the role of magnetic resonance imaging. AB - The article describes a patient with a right paratracheal bronchogenic cyst in whom the preoperative diagnosis was unclear. The fluid component of the cyst was not readily apparent by CT or T1-weighted MR images. Very intense signal on T2 weighted MR images suggested a cystic lesion. Inhomogeneities evident on MR but not CT images provided further soft tissue characterization. These soft tissue elements correlated with a macroscopic ring of hyaline cartilage in the resected specimen. The usefulness of MRI for the differential diagnosis of mediastinal tumors is discussed. PMID- 1856902 TI - Pulmonary hemorrhage in patients with systemic lupus erythematosus. AB - Five patients with pulmonary hemorrhage associated with SLE were studied. Chest radiographs showed extensive alveolar opacity immediately after hemoptysis or dyspnea in four patients. In one patient an interstitial pattern seen initially progressed rapidly to an alveolar pattern. Three patients were successfully treated with corticosteroids and are doing well at present. The diagnosis and treatment of pulmonary hemorrhage is vital to patients with SLE. In the appropriate clinical setting chest radiographic findings of acute alveolar disease should suggest pulmonary hemorrhage, and empiric treatment with corticosteroids should be considered. PMID- 1856903 TI - Evaluation of pulmonary vascular pressures in cardiac patients: the role of the chest roentgenogram. AB - In 77 patients (34 with left heart valvulopathy, 17 with dilated cardiomyopathy, and 26 with chronic coronary artery disease) pulmonary vascular pressures were estimated from the chest film by means of a new scoring system. Standard chest x ray films taken immediately before diagnostic right and left cardiac catheterization were analyzed independently by three readers without knowledge of the hemodynamic findings. The radiographic signs were subdivided into three groups as follows, and to each one a score derived from a retrospective statistical analysis was attributed: (A) signs of interstitial edema, (B) patterns of pulmonary blood flow distribution, and (C) alterations in the pulmonary arteries. The sum of the scores of groups A and B x-ray findings correlated well with pulmonary wedge pressure, and the sum of the scores of groups A, B, and C correlated more strongly with the mean pulmonary artery pressure. These results confirm that it is possible, in patients with chronic heart disease, to assess accurately the pulmonary artery and wedge pressures by means of the noninvasive and easily performed chest roentgenogram. PMID- 1856904 TI - Polysplenia syndrome in the asymptomatic adult: computed tomography evaluation. AB - Although the majority of patients with polysplenia syndrome will present during infancy or childhood with congenital heart disease, 5% to 10% will have no cardiac disease; and the associated abnormalities may not be discovered until adulthood. Physicians should be familiar with the chest and abdominal radiographic findings so as not to confuse this syndrome with other, more common pathologic conditions in asymptomatic adult patients. PMID- 1856905 TI - Lung abscess caused by Rhodococcus equi. AB - In the immunocompromised patient, early diagnosis of a lung cavity is essential for appropriate treatment. Rhodococcus equi (formerly Corynebacterium equi) is a variably acid-fast bacterium that can produce cavitary disease in an immunocompromised host. The two cases presented here demonstrate the clinical and radiographic features of R equi lung abscess. The first patient was on long-term corticosteroid therapy for rheumatoid arthritis. The second patient had AIDS. The correct diagnosis in both cases was delayed because acid-fast bacilli seen on smears of sputum were presumed to be Mycobacterium tuberculosis. PMID- 1856906 TI - Transcatheter detachable balloon embolotherapy for catheter-induced pulmonary artery pseudoaneurysm. AB - Pulmonary artery pseudoaneurysm formation may be due to various etiologies, including trauma, pulmonary artery catheterization, infection, and tumor. Transcatheter embolization is a nonsurgical management technique that may be utilized in many of these patients to occlude the affected artery and to prevent further extravasation. Recently, two patients with pulmonary artery pseudoaneurysm formation after balloon-tipped catheter placement were successfully managed with transcatheter embolotherapy with detachable silicone balloons. The article describes their diagnosis and management. PMID- 1856907 TI - Sports psychology. PMID- 1856908 TI - Failure of caffeine to affect metabolism during 60 min submaximal exercise. AB - Caffeine consumption prior to athletic performance has become commonplace. The usual dosage is approximately 200 mg, a level of caffeine ingestion equivalent to two cups of brewed coffee. This study was designed to examine the effects of a common level of caffeine ingestion, specifically 200 mg, on metabolism during submaximal exercise performance in five males. The subjects performed two 60-min monitored treadmill workouts at 60% maximal heart rate during a 2-week period. The subjects were randomly assigned, double-blind to receive a caffeine or placebo capsule 60 min prior to exercise. Testing was performed in the afternoon following a midnight fast. Venous blood was withdrawn pre-exercise, every 15 min during the workout, and 10 min after recovery. Blood was analysed for free fatty acid, triglycerides, glucose, lactic acid, haemoglobin and haematocrit. The respiratory exchange ratio (R), perceived exertion (RPE) and oxygen uptake were measured every 4 min during exercise. An examination of the data with repeated measures ANOVA revealed no significant differences between the two groups. Within the limitations of the study, it was concluded that 200 mg caffeine failed to affect metabolism during 60 min submaximal exercise. PMID- 1856909 TI - Anthropometric characteristics as discriminators of body-building success. AB - A total of 36 non-elite male body builders were observed at the time of competition. Their mean physical characteristics (+/- S.D.) were: age, 24.6 +/- 4.8 years; height, 174.4 +/- 6.7 cm; bodyweight, 80.3 +/- 11.0 kg. Their body composition values were: percentage body fat, 9.3 +/- 1.6%; fat-free mass, 72.8 +/- 9.8 kg. The mean somatotype for all subjects was: endomorphy, 2.3 +/- 0.6; mesomorphy, 6.2 +/- 0.9; ectomorphy, 1.2 +/- 0.6. The body proportions (cm) included: biacromial diameter/bi-iliac diameter, 1.463 +/- 0.132; torso length/height, 0.468 +/- 0.018; chest circumference/abdominal circumference, 1.345 +/- 0.059. The body builders in the present study were younger, had lower bodyweights, lower fat-free mass, lower mesomorphy ratings, smaller circumferences, and smaller skeletal dimensions than elite body builders reported in the scientific literature. When the body builders in the present study were divided into successful and unsuccessful groups based on actual competition results, a multiple-discriminant analysis found that biacromial diameter/bi-iliac diameter, torso length/height, chest circumference/abdominal circumference, percentage body fat, height, and bodyweight accounted for 80.6% of the explained variance. These data indicate that the success of a body builder can be accounted for in large part by easily obtained physical variables. PMID- 1856911 TI - Effect of floor conditions upon frictional characteristics of squash court shoes. AB - Vertical (FN) and horizontal (FH) forces were recorded while four vertically loaded court shoes were dragged horizontally across six types of floor surface. Variation in coefficient of limiting friction (FH/FN) between floor surfaces was greater than that between shoes. Squash strokes were also performed on the same surfaces during which FH/FN was calculated. Slips occurred on some surfaces either at heel contact or upon attainment of full-sole contact. It is concluded that the coefficient of limiting friction obtained during full-sole contact with the floor is a suitable means of distinguishing between tractional qualities of shoes. Alternatively, this measure is an inadequate predictor of the likelihood of slips in the game of squash racquets. Dusty floor conditions produce poor traction as does a damp sealed floor. As sweat droplets are unavoidable in the game, floors sealed with urethane represent a significant hazard. Bare, clean, wooden flooring which can absorb moisture represents a better surface than a sealed floor from the point of view of traction. PMID- 1856910 TI - Maximal exercise performance and lean leg volume in men and women. AB - The purpose of this study was to compare the maximal exercise performance during cycle ergometry of 34 men and 47 women. External peak power output (OPP) and optimized pedalling rate (ORPM) were calculated from data gathered during an optimization procedure performed on a friction braked cycle ergometer. In addition, lean leg volume (LLV) and lean upper leg volume (LULV) were determined using an anthropometric technique. Both OPP and ORPM were greater in men than in women (1007 +/- 135 vs 673 +/- 109 W and 119.5 +/- 7.0 vs 104.5 +/- 8.4 rev min 1, respectively; P less than 0.001). The LLV and LULV were also greater in men than in women (7.41 +/- 0.82 vs 5.19 +/- 0.85 l and 4.96 +/- 0.63 vs 3.35 +/- 0.62 l, respectively; P less than 0.001). The ratio standards OPP/LLV and OPP/LULV did not differ significantly between men and women (136.3 +/- 14.7 vs 131.0 +/- 20.6 W l-1 and 204.4 +/- 27.1 vs 204.4 +/- 37.0 W l-1, respectively; P greater than 0.05). Peak power output was related to each of the anthropometric indices in both men and women (LLV:r = 0.614 and 0.527, P less than 0.001; LULV:r = 0.489 and 0.396, P less than 0.01). Analysis of covariance revealed no significant differences between the groups in the variance about regression and the regression coefficients (P greater than 0.05), but the elevation of the regression lines did differ (P less than 0.001). The results suggest that there are differences between maximal exercise performance in men and women that are independent of estimated lean leg volume. They also demonstrate that, in this case, consideration of ratio standards is misleading and that a comparison of regression standards is more appropriate. PMID- 1856912 TI - Maximal oxygen uptake and work capacity after inspiratory muscle training: a controlled study. AB - The effect of inspiratory muscle training for 10 min twice a day for 27.5 days was evaluated in 20 human subjects, of whom 10 formed a training group and 10 a sham training group. The maximal oxygen uptake (VO2 max), maximal ventilation, breathing frequency during maximal exercise and the distance run in 12 min on a track were determined in addition to resting peak expiratory flow, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), with alveolar oxygen tension (pAO2) during maximal exercise being calculated. Inspiratory muscle training increased maximal inspiratory pressure from 93 (range 38-118) to 110 (65 165) mmHg in the training group (P less than 0.0005), but did not affect VO2 max, ventilation during maximal exercise, peak expiratory flow, FEV1 or FVC. However, breathing frequency during maximal exercise decreased slightly from 56 (44-87) to 53 (38-84) breaths min-1 (P less than 0.05) in the training group only; but the calculated pAO2 did not increase from the pre-training value of 126 (116-132) mmHg. The maximal distance run during 12 min increased similarly in the training and sham training groups by 8% (3-12%) and 6% (2-12%), respectively (P less than 0.01). The results of this study show that inspiratory muscle training resulting in a 32% (0-85%) increase in maximal inspiratory pressure does not change FEV1, FVC, peak expiratory flow, VO2 max or work capacity. PMID- 1856913 TI - Anthropometric characteristics of outstanding male and female gymnasts. AB - Anthropometric data of outstanding gymnasts were gathered on the occasion of the 24th World Championship Artistic Gymnastics, held at Rotterdam, The Netherlands, in October 1987. In total 165 males and 201 females were investigated, constituting 84% of the total number of participants. The data of these gymnasts were descriptively compared with both reference data and data reported in previous studies on gymnasts competing at international events. Also, based on the data obtained, 'gymnastic-specific' anthropometric reference values (i.e. profile charts), were established for both male and female gymnasts. Finally, the maturational characteristics (skeletal age and menarche) of the 'Rotterdam' female gymnasts were described. PMID- 1856914 TI - Pelvic lipomatosis: a review of its diagnosis and management. PMID- 1856915 TI - Evaluation and treatment of blunt renal trauma. AB - We examined retrospectively the records of 126 patients with blunt renal trauma to determine the criteria for radiological investigations and the imaging study of choice. Of the 3,993 patients admitted to our regional trauma unit during the last 13 years 126 (3.1%) had blunt renal trauma. Mean patient age was 32 years (range 13 to 87 years) and the male-to-female ratio was 3:1. Mean followup was 7 months (median 4 months). Of the patients 72% had a minor renal injury, 17% had a moderate injury and 11% had a major renal injury. Treatment was conservative in 114 patients, while 9 underwent a genitourinary operation. Results were excellent in 87% of the patients and good in 8%, while 5% failed treatment. All patients who had microscopic hematuria without shock had minor injuries. Excretory urograms (IVPs) were normal in 74% and 39% of the patients when performed for minor and moderate renal injuries, respectively. Computerized tomography (CT) was abnormal in all cases when performed, and was more sensitive and specific than an IVP. Therefore, the majority of patients with blunt renal trauma can be treated conservatively with an excellent result. Furthermore, radiological investigations are not needed in those with microscopic hematuria and no shock. When radiological investigations are indicated a CT scan is the imaging study of choice. PMID- 1856916 TI - Stryker frame gantry modification for extracorporeal shock wave lithotripsy to circumvent positioning problems. AB - From July 1986 through December 1989, 45 patients with renal or biliary calculi were treated on a Dornier HM3* lithotriptor using a Stryker frame gantry modification. The modification was necessary due to inability to position the patients in the standard gantry. The situations that required nonstandard positioning techniques included stones in the distal or mid ureter, renal transplant, gallbladder or common bile duct, and unusual body habitus, such as myelomenigocele, bilateral lower extremity amputations and children with stones. Positioning with adequate focus of the shock wave was achieved in 87% of the patients and fragmentation was achieved in 89%. The Stryker frame gantry modification is an excellent method to circumvent positioning problems with the Dornier HM3 lithotriptor, extending lithotripsy capability to patients who might otherwise not be candidates. PMID- 1856917 TI - The use of local anesthesia in second generation extracorporeal shock wave lithotripsy: eutectic mixture of local anesthetics. AB - Extracorporeal shock wave lithotripsy (ESWL&) can be painful. Of our population of patients treated with a Siemens Lithostar device 51.4% needed intravenous analgesia. A eutectic mixture of local anesthetics, a hydrophylic cream containing 25 mg. lidocaine and 25 mg. prilocaine per gm., proved to be effective for local analgesia. Therefore, we investigated its effectiveness during ESWL. With randomized, double-blind application the eutectic mixture of local anesthetics and placebo were evaluated in 83 patients according to the percentage of patients who required intravenous analgesia during ESWL. Of 40 patients treated with the eutectic mixture of local anesthetics 12 (30%) needed supplementary fentanyl citrate, compared to 23 of 43 (53%) placebo treated patients. Although there is no statistical significance (p = 0.32), the eutectic mixture of local anesthetics does decrease pain during ESWL and it should be particularly useful for patients in whom intravenous analgesia is contraindicated. PMID- 1856918 TI - Equivalence of mobile and fixed lithotriptors for upper tract stones. AB - Although mobile renal lithotripsy appears to be a cost-efficient method for a urologist to treat patients at the local hospital the quality issue has been raised with occasional use of a mobile lithotriptor. We reviewed 4,278 kidneys in 3,900 patients treated by 129 urologists using a mobile Dornier HM3 and a mobile Medstone lithotriptor at 21 mobile sites in 6 upper midwest states during 3 1/2 years. These results were compared with those in 524 kidneys in 480 patients treated by our fixed Medstone lithotriptor. After the procedure auxiliary treatments were needed in 3% of the patients treated with the mobile units and 2% of those treated with the fixed unit. The rate in 2 large published series was approximately 9%. The retreatment rates were 5% with the mobile lithotriptors and 6% with the fixed (reported average 16%), and the over-all stone-free rates at 3 months were 69% and 68% (versus 66%). Of note, the mobile units were as effective as the fixed unit against difficult stones. A mobile lithotriptor with a constant support staff that is used 1 or 2 times per month by many trained urologist will perform as well as fixed lithotriptor used regularly by a small unvarying staff of trained urologists. PMID- 1856919 TI - Comparative studies of extracorporeal shock wave lithotripsy by Dornier HM3, EDAP LT 01 and Sonolith 2000 devices. AB - During a 2-year period extracorporeal shock wave lithotripsy (ESWL) was done at our institution in 70 patients with the Dornier HM3, 113 with the EDAP LT 01 and 104 with the Sonolith 2000 lithotriptors. The size and location of stones were comparable in all 3 series, and all treatments were done by the same team of urologists. Complete fragmentation occurred in 79% of the patients treated by the Dornier, 82% treated by the EDAP and 79% treated by the Sonolith devices, with 3 month stone-free rates of 66, 67 and 58%, respectively. Auxiliary procedures were needed in 12% of the patients in the Dornier, 13% in the EDAP and 9% in the Sonolith groups. Repeat treatment was necessary in 4% of the Dornier group, 42% of the EDAP group and 26% of the Sonolith group. Therefore, all 3 lithotriptors are effective in stone disintegration and produce satisfactory results when selection criteria for ESWL are observed. The most significant difference among the 3 lithotriptors is the number of repeat treatments, which reflects the power and energy output of the lithotriptors. In conclusion, the Dornier HM3 device has the advantage of low repeat treatment rate and easier stone localization. The EDAP LT 01 unit has the advantage of lower treatment costs and anesthesia-free treatment with no irradiation. The Sonolith 2000 device has features of the other 2 lithotriptors with a superior ultrasound image. PMID- 1856921 TI - Ileal segment for ureteral substitution or for improvement of ureteral function. AB - A total of 29 patients received an ileal segment interposition between the upper and lower urinary tract for partial or total ureteral substitution, or for ileal wrapping around a massively dilated, aperistaltic ureter. Indications for an operation included the presence of an extensively diseased or short ureter and an aperistaltic megaureter that had failed previous reconstructive attempts. Nine patients (group 1) underwent an ileal sleeve procedure in an attempt to increase the ureteral peristaltic activity and facilitate drainage. Among these patients 7 (78%) had a stable upper tract radiologically and normal serum creatinine (less than 1.6 mg./100 ml.), while 2 (22%) had deterioration of the renal function. Ten patients (group 2) had undergone a myriad of reconstructions that failed and then underwent complete ureteral substitution with ileum. Among them, renal function (as evidenced by excretory urography and serum creatinine) is stable in 7 (70%) and deteriorated in 3 (30%). In 10 patients (group 3) the ureters were partially replaced by ileum in addition to a bladder augmentation procedure. Of these patients 8 (80%) have stable renal function and 2 (20%) had renal failure. Over all, 7 patients have different degrees of renal failure; among them 2 (6.9%) are on dialysis and 2 (6.9%) have received a transplanted kidney. In groups 2 and 3 the results with an antireflux operation indicated that among 6 ureteroileal reimplantations 5 (83%) were successful, among 12 intravesical intestinal nipples 6 (50%) failed to prevent reflux and there was no case of obstruction, while among 4 ileocecal intussusceptions 2 (50%) were successful and 2 failed. Mucous secretion produced temporary ureteral obstruction in 1 ureter (3.4%), which resolved without surgical intervention. Some of the aforementioned procedures were done in the past and in some situations a different reconstructive technique would be considered presently. The surgical complexity and magnitude of the procedures justify their performance only in difficult clinical situations as an alternative to urinary diversion or renal autotransplantation. PMID- 1856920 TI - Sonographic visualization of the ureter in pregnancy. AB - We describe a method of differentiating physiological from pathological dilatation of the renal collecting system in pregnant patients. In physiological hydronephrosis the dilated ureter extends down only to the level of the common iliac artery. In 2 patients with distal ureteral stones a dilated ureter was visualized past the vessels. To determine the frequency and reliability of visualizing the ureters in pregnant patients 105 consecutive asymptomatic pregnant patients were examined. Hydronephrosis was found in 83 kidneys in 59 of the patients. The dilated ureter was visualized in 64 of the renal units. The anatomy was well demonstrated by color flow Doppler scanning and in all of these cases the dilated ureter was seen to taper where it crossed the common iliac artery. These results suggest that the presence of a dilated ureter past the iliac artery is strong evidence for pathological distal ureteral obstruction in pregnancy. PMID- 1856922 TI - Optimization of replacement of the ureter by ileum. AB - Fifty patients for whom an ileal replacement of the ureter was indicated were prospectively randomized among 2 treatment groups according to the surgical technique used. In group 1 the standard operation was performed. In group 2 a tailored and valved (modified) ileal ureter was used. Patients were followed every 3 to 6 months for 12 to 28 months. Kidney functions were evaluated by 99m technetium diethylenetriaminepentaacetic acid scans and by determination of the 24-hour creatinine clearance. Urine cultures were obtained, and urine viscosity and flow rates were measured. A urographic study, including ascending cystography, was done every 6 months. Results indicated that the modified operation is functionally superior to the standard procedure. It provides efficient unidirectional flow of urine from the kidney to the bladder with less mucus secretion. This was ultimately reflected as better renal function when it was quantitated by renography and/or chemical clearance. PMID- 1856923 TI - Neobladder construction using completely detubularized sigmoid colon after radical cystoprostatectomy. AB - To improve the quality of life of the patient we used completely detubularized sigmoid colon for bladder reconstruction along with radical cystoprostatectomy in 6 men with invasive bladder cancer. Followup was 8 to 20 months. Postoperatively, all of the patients were continent during the day but only 4 (66.7%) were continent at night, although they had to awaken twice to remain dry. Neocystourethroscopy in 4 of the 6 patients revealed no tumor and no stricture at the urethrocolonic anastomosis. However, a stone in the neobladder was found in 1 patients. Urodynamic study of the neobladder showed a low pressure (mean 16.7 cm. water) at the filling phase of water cystometry and an adequate maximal urethral closure pressure (mean 52.0 cm. water) and functional profile length (mean 3.8 cm.). The uroflow rate in all patients was good (1 patient even had a maximal uroflow rate of 31 ml. per second). There was no reflux in any patient. One patient had intestinal obstruction 5 months postoperatively and died 5 months later of widespread metastasis. The remaining 5 patients are alive with a satisfactory quality of life. In conclusion, use of completely detubularized sigmoid colon may be an ideal operation for neobladder construction after radical cystoprostatectomy. PMID- 1856924 TI - Residual tumor discovered in routine second transurethral resection in patients with stage T1 transitional cell carcinoma of the bladder. AB - When a second transurethral resection was routinely performed 8 to 14 days after the initial transurethral resection in 46 patients for stage T1 bladder tumors residual disease was found in 20 despite the surgical report of complete resection in 40. In only 13 patients was residual tumor noted at repeat resection by the senior urologist performing the operation and residual tumor was confirmed histologically in 10 of them. The extent of the lesion is easily misjudged even by experienced surgeons. Early cystoscopy cannot exclude residual tumor. Residual tumor is an important cause of early recurrence and repeat resection of stage T1 lesions is recommended. PMID- 1856925 TI - Particle shedding and migration from silicone genitourinary prosthetic devices. AB - Of 26 patients undergoing revision of genitourinary prostheses the surrounding reactive fibrous capsule was biopsied in 25 and the draining lymph nodes also were biopsied in 4. The prostheses included 16 inflatable and 14 flexible penile devices, and 10 artificial urinary sphincters. Tissue was examined by light and transmission electron microscopy. X-ray microanalysis was done on intracellular and extracellular foreign material from each specimen. Silicone was found in 18 of the 25 periprosthetic specimens and in all 4 lymph nodes. Foreign body granulomas were identified in 14 of these 29 specimens. Examination of new and explanted versions of each prosthesis by scanning electron microscopy revealed free particles of silicone or silicates on the surface of most devices. Pitting and microfissuring were seen on a few of the new devices and on nearly all of the used ones. Thus, genitourinary prostheses shed silicone particles that can be found in the fibrous capsule and draining lymph nodes. PMID- 1856926 TI - Treatment of pharmacological priapism with phenylephrine. AB - Pharmacological prolonged erections or priapism due to anesthesia were treated in 36 patients with intracorporeal injections of phenylephrine. Detumescence was obtained rapidly in every case and no marked side effect was reported. Considering the possible toxicity of other adrenergic agents, phenylephrine is strongly recommended in the treatment of priapism. PMID- 1856927 TI - The surgical treatment of chordee without hypospadias in men. AB - During a 2-year period we treated 26 young men for chordee without hypospadias. Many of these patients had straight erections as children but a ventral curvature developed as they achieved puberty. We describe the anatomical findings and discuss the possible cause for the development of this anomaly. Surgical therapy begins with a circumcising incision and reflection of the skin to expose the shaft of the penis. The corpus spongiosum containing the urethra was mobilized by resecting the dysgenetic tissue in the dartos and Buck's fascia layers. In 1 patient this dissection was sufficient to straighten the penis but in the remaining 25 the penis was not straight. In those patients we mobilized the dorsal bundle of vessels and nerves, and removed 1 or several ellipses of tunica albuginea to equalize the lengths of the ventral and dorsal aspects of the corpora cavernosa. The corpus spongiosum usually is elastic and the curve almost never is caused by shortness of the urethra, which stretches to fit the straightened penis. In 24 of the 26 patients the curvature was resolved with 1 operation, while 2 needed a second procedure. PMID- 1856928 TI - Acquired immunodeficiency syndrome-related Kaposi's sarcoma of the male genitalia: management with radiation therapy. AB - Kaposi's sarcoma of the genitalia is an infrequent complication of the acquired immunodeficiency syndrome but it often is difficult to manage. A total of 19 men (mean age 39 years) with penile and/or scrotal lesions underwent radiotherapy at dosages of 600 to 3,000 cGy. in fractions of 150 to 800 cGy. Of the patients 6 achieved a complete and 10 a partial response, while 2 had no response and 1 died too soon after treatment to be evaluated. Recurrences were noted in 8 patients, 7 of whom received additional radiation (1 patient had 2 recurrences and both responded). Of the retreatments 3 effected complete and 4 partial responses. Over all, of 25 evaluable treatment courses 9 complete (36%) and 14 partial (56%) responses yielded a total response rate of 92%. There was 1 complication, a skin ulceration. Radiation therapy is well tolerated and will result in effective palliation in the majority of patients with Kaposi's sarcoma of the genitalia. PMID- 1856929 TI - Quantitative testicular biopsy in spinal cord injured men: comparison to fertile controls. AB - Spermatogenic abnormalities have been reported in the majority of spinal cord injured men on routine testicular biopsy. However, given the interim advances in their urological and rehabilitative care, a quantitative assessment of the germinal epithelium after spinal cord injury and comparison of these parameters to normal controls are warranted. Incisional testicular biopsy was performed in 14 spinal cord injured men. Quantitative micrometric techniques were applied to assess spermatogenesis and the results were compared to a normative data base of testicular biopsies previously obtained from a group of 15 fertile volunteers. From a minimum of 10 randomly selected round seminiferous tubules per subject the mean number of Sertoli cells, mature spermatids, tubular diameter and tubular wall thickness were determined in both groups and statistically analyzed. In the spinal cord injury group the mean number of spermatids per tubule was significantly lower and the mean number of Sertoli cells per tubule was significantly higher than in fertile controls (p less than 0.05). Moreover, the mean Sertoli cell-to-spermatid ratio per seminiferous tubule was significantly higher in the spinal cord injury group and discriminated between spinal cord injured men and controls, with a sensitivity of 93% and specificity of 100% (p less than 0.0001). Half of the spinal cord injury group showed a mean tubular spermatid density of less than 10. Compared to the fertile population, spinal cord injured men show significant differences in quantitative parameters of the germinal epithelium that may contribute to the reproductive dysfunction. PMID- 1856930 TI - Refractory chronic bacterial prostatitis: a re-evaluation of ciprofloxacin treatment after a median followup of 30 months. AB - A total of 16 men suffering from refractory chronic bacterial prostatitis caused by Escherichia coli was treated with ciprofloxacin for 4 weeks. After a median followup of 30 months (range 21 to 36 months) 10 of the 16 patients were considered cured as judged by bacteriological results and clinical symptoms. In 2 men a second ciprofloxacin regimen obviously showed success also. In 2 patients ciprofloxacin therapy failed and in 2 therapy had to be discontinued due to side effects of the central nervous system. PMID- 1856931 TI - Elevated plasma chromogranin-A concentrations in prostatic carcinoma. AB - Chromogranin-A is considered a sensitive immunohistochemical tissue marker in neuroendocrine prostatic carcinoma. We report that the plasma chromogranin-A level was elevated in 48% of 25 patients with stage D2 prostate cancer, and suggest that this marker can be used to monitor the clinical course of these patients. PMID- 1856932 TI - Effect of temporary occlusion of hypogastric arteries on blood loss during radical retropubic prostatectomy. AB - We report on a prospective, partially randomized study of 130 patients, examining the effect of temporary occlusion of the hypogastric arteries on intraoperative blood loss, perioperative blood replacement and change in preoperative to postoperative hematocrit. We observed no significant difference in any of these parameters when comparing patients who did and did not undergo intraoperative occlusion of the hypogastric arteries. These findings suggest that temporary occlusion of the hypogastric arteries during radical prostatectomy does not have a major effect on the blood loss associated with this operation. Extensive collateral circulation to the prostate and a substantial venous component of blood loss may explain these findings. Banking of 3 units of autologous blood preoperatively would have decreased the need for homologous transfusions in the majority of patients. PMID- 1856933 TI - Transrectal ultrasonography in stage A prostate cancer: detection of residual tumor after transurethral resection of prostate. AB - To evaluate the ability of transrectal ultrasonography to detect residual cancer in the prostate gland after transurethral resection in patients with stage A cancer, we studied 38 patients with stage A disease (11 stage A1 and 27 stage A2) in whom transrectal ultrasonography was done at least 3 weeks after resection. Each patient underwent radical prostatectomy, and residual cancer was present in 97% of the specimens (peripheral zone cancer in 95% and transition zone cancer in 61%). At sonography we identified hypoechoic areas suggestive of cancer in 10 patients (26%). In the pathological specimen residual cancer was present at the hypoechoic area in 8 of these cases (positive predictive value 80%). In a retrospective review of the sonograms we identified 25 hypoechoic lesions greater than 5 mm. in diameter, including 15 that corresponded to cancer in the radical prostatectomy specimens (positive predictive value 60%). Granulomas due to the transurethral resection were found in 92% of the radical prostatectomy specimens but none appeared hypoechoic on ultrasound. A total of 103 separate cancers was identified in the whole mount step sections of the radical prostatectomy specimens (2.7 cancers per patient). Of the 103 separate cancers 54 were less than 0.1 cc in volume and none of these could be identified in the retrospective review of the sonograms, 37 were 0.1 to 1.0 cc and 5 of these (14%) appeared hypoechoic, and 12 were greater than 1.0 cc and 10 of these (83%) appeared hypoechoic. Hypoechoic lesions greater than 5 mm. in diameter in the transition zone proved to be cancer in 47% of the cases, while 88% of similar lesions in the peripheral zone proved to be cancer. We conclude that suspicious-appearing hypoechoic lesions suggestive of cancer, whether in the peripheral zone or the transition zone, should be biopsied before expectant management of stage A prostate cancer is considered. Transrectal ultrasonography is useful for restaging after transurethral resection and for evaluating the extent of residual cancer in stages A1 and A2 prostate cancer. PMID- 1856934 TI - Analysis of prognostic factors in men with metastatic prostate cancer. Uro Oncology Group of Northern Alberta. AB - We determined the influence of the extent of disease on bone scan, serum testosterone, patient age, performance status, method of initial diagnosis, Gleason grade, clinical stage at diagnosis, serum acid phosphatase, serum prostate specific antigen (PSA) and primary hormonal treatment on survival. The clinical and hormonal data were obtained when the presence of metastatic disease was established and treatment was to be initiated in 162 men with metastatic prostate cancer. Mean followup was 16 months (range 1 to 105 months). A total of 70 men (43.2%) died of the metastatic disease during the evaluation period. Log rank analysis revealed that only serum testosterone (p = 0.035) and extent of disease on bone scan (p = 0.003) significantly affected over-all survival. A trend (p = 0.068) towards decreased survival was observed with increasing values of PSA. Increasing values of acid phosphatase positively correlated with extent of disease on bone scan but was not a significant independent prognostic factor. Patient age, performance status, clinical stage, method of initial diagnosis, Gleason grade and type of hormonal treatment did not significantly influence survival. Upon using multivariate Cox analysis, only extent of disease on bone scan was significantly correlated with over-all survival (p less than 0.014). PSA may also be influential but longer duration of followup will be necessary. We conclude that extent of disease on bone scan is the most important prognosticator of the analyzed factors and that serum testosterone may be of value. PMID- 1856935 TI - Monotherapy with nilutamide, a pure nonsteroidal antiandrogen, in untreated patients with metastatic carcinoma of the prostate. The Italian Prostatic Cancer Project. AB - A total of 26 previously untreated patients with metastatic carcinoma of the prostate received the pure nonsteroidal antiandrogen nilutamide as a single agent. Objective response rate was 38.5 +/- 18.7% (95% confidence interval). Median progression-free survival and median survival were 9 and 23 months, respectively. Of 13 patients with progression on antiandrogen 5 showed an additional objective response to a second-line endocrine treatment. The drug was generally well tolerated, except for 2 patients who discontinued treatment because of moderate gastrointestinal symptoms. Approximately a third of the patients complained of decreased adaptation to darkness. An electroretinogram and dark adaptation test revealed the presence of functional damage and visual complaints reversed in all patients on cessation of therapy. The other most frequent side effects were slight nausea (26.9% of the patients) and alcohol intolerance (19.2%). A nonsignificant increase in testosterone levels was shown within 1 month of treatment, after which the levels remained stable. Approximately half of the sexually active men claimed maintenance of libido and sexual potency during treatment. A slightly significant increase in hemoglobin was observed during the long term, suggesting the occurrence of a trophic effect by androgens on erythropoiesis. The results indicate that nilutamide as a single agent has an acceptable toxicity and a moderate activity, and may maintain sexual interest in a discrete number of cases. Whether monotherapy with nonsteroidal antiandrogens offers a valid option in the palliation of advanced disease remains to be seen in comparative prospective trials. PMID- 1856936 TI - The urology crash box. PMID- 1856937 TI - An improved expanding tip urethral suture guide for use in radical prostatectomy. PMID- 1856938 TI - Traumatic disruption of the ureteropelvic junction managed by ileal interposition. AB - The use of ileal interposition in the management of a patient with delayed diagnosis of traumatic disruption of the ureteropelvic junction is presented. The unusual presentation of this problem, potential options in reconstructing the ureter and successful outcome are discussed. PMID- 1856939 TI - The long-term results of artificial sphincters in children. AB - To determine the long-term efficacy of the artificial urinary sphincter, 36 consecutive children in whom a prosthesis was implanted between August 1978 and July 1985 were followed for a minimum of 5 years and re-evaluated within the last 3 months. Of the 36 sphincters 27 (75%) are currently in place; 2 of these 27 sphincters are dysfunctional due to fluid leakage. Of the 25 functioning sphincters 14 have required no further prosthetic operation, 10 needed 1 revision and 1 patient had 5 revisions. Fluid leakage, occurring in 12 patients, was the most common complication requiring reoperation. Twenty patients are completely continent (11 of whom without any medication) and 5 are occasionally damp. The over-all success rate at 2 and 5 years was 84 and 62%, respectively. The mean survival time of the prosthesis was 7.2 years and the mean standard interval was greater than 10.5 years. Patients with higher balloon pressures (81 to 100 cm. water) had more complications, and a decreased rate of success than those with lower pressure balloons (51 to 80 cm. water, p = 0.02). There was no difference in success rates between boys and girls (p = 0.98), although girls who had a prior bladder neck operation tended to have a higher rate of cuff erosion. Sphincters placed after 1980 (model AS800) had a lower reoperation rate than those placed earlier. In selected instances, the artificial urinary sphincter appears to be a viable long-term alternative for management of children with intractable incontinence who have either failed or are unsuitable for other methods of treatment. PMID- 1856940 TI - Adrenal hemangioma: an unusual adrenal mass delineated with magnetic resonance imaging. AB - Adrenal hemangioma should be included in the differential diagnosis of any large calcified adrenal mass. We report to our knowledge the eighth surgically removed lesion and describe its appearance on magnetic resonance imaging. This imaging includes features seen in hemangiomas elsewhere, in particular a heterogeneous mass with enhancing peripheral high intensity foci on T1 images. PMID- 1856941 TI - Noninvasive radiological diagnosis of renal vein thrombosis in renal transplantation. AB - Thrombosis of the allograft renal vein is a rare complication of renal transplantation. Of 557 consecutive renal transplants performed between January 1, 1985 and November 30, 1989, 3 cases occurred for an over-all incidence of 0.4%. In 2 cases the diagnosis was made preoperatively with renal scintigraphy and duplex Doppler sonography. No graft was salvaged, despite timely diagnosis in 2 patients. We conclude that the diagnosis of renal vein thrombosis in the renal allograft recipient should be suspected clinically and by the radiographic findings of absent perfusion on renal scintigraphy, and the detection of an arterial signal, albeit abnormal, on duplex Doppler sonography. When diagnosed, nephrectomy appears to be the only treatment. PMID- 1856942 TI - Renal pelvic explosion during conservative management of upper tract urothelial cancer. AB - Ureteroscopic fulguration of a renal pelvic papillary transitional cell carcinoma is a relatively new and limited procedure. We present a case of intrarenal explosion during ureteroscopic fulguration. PMID- 1856943 TI - The use of extracorporeal shock wave lithotripsy in patients with aortic aneurysms. AB - Extracorporeal shock wave lithotripsy (ESWL*) has revolutionized management of most patients with urolithiasis. The effect of ESWL on patients with an aortic aneurysm is unknown and its safety is questioned by the absence of any case reports in the urological literature. A 68-year-old man with an abdominal aortic aneurysm underwent successful ESWL using the Medstone STS 1050 lithotriptor for right renal calculi. Continuous monitoring of the aneurysm was done using real time ultrasound during the ESWL treatment. Careful preoperative evaluation in conjunction with appropriate intraoperative and postoperative monitoring makes ESWL management of patients with associated aortic aneurysm possible. PMID- 1856945 TI - Short arm dicentric Y chromosome in a sterile man: a case report. AB - A short arm dicentric Y chromosome as the predominant cell line in a sterile man is reported. We studied a 33-year-old sterile man whose seminiferous tubules had only Sertoli cells. Chromosomal analysis, using G, Q and C-banding techniques, showed that the predominant cell line had a short arm dicentric Y chromosome. By the deoxyribonucleic acid probe pHY10, the lack of the gene corresponding to the Yq heterochromatic and distal Yq euchromatic region was detected. It is suggested that the gene controlling spermatogenesis is located on the distal euchromatic region on Yq. PMID- 1856944 TI - Ureteronephroscopic marsupialization of obstructing peripelvic renal cyst. AB - Flexible ureteronephroscopy has been used for numerous therapeutic applications in the upper urinary tract. We report a case of a large peripelvic renal cyst causing obstruction to the ureteropelvic junction, which was treated by incising the wall of the cyst into the renal pelvis with the ureteronephroscope. PMID- 1856946 TI - Prostatic abscess after transrectal ultrasound guided biopsy. AB - We report a case of a diabetic man who had bilateral prostatic abscesses after ultrasound guided biopsy of the prostate. As is typical of prostatic abscesses, the diagnosis was not evident at presentation. We discuss the morbidity of transrectal biopsy and recommend consistent antimicrobial prophylaxis. We also recommend transrectal ultrasound in the diagnosis of such abscesses, and support the standard treatment of drainage and parenteral antimicrobial therapy. We anticipate that the incidence of prostatic abscess will increase due to the increasing number of men undergoing transrectal biopsy in the current age of transrectal ultrasound guided biopsy. PMID- 1856947 TI - Congenital keratinizing desquamative squamous epithelium of the entire urinary tract. AB - We report the clinical and pathological findings of a case of congenital desquamative squamous epithelium of the entire urinary tract associated with body dysmorphism. This entity has not been described previously in the literature. PMID- 1856948 TI - Re: Bilateral synchronous testis tumors of different histology in a patient with the acquired immunodeficiency syndrome related complex. PMID- 1856949 TI - Type IV procollagen mRNA regulation: evidence for extracellular matrix/cytoskeleton/nuclear matrix interactions in human urothelium. AB - The absence of basement membrane components correlates with tumor stage and progression in human bladder cancers. We have previously shown that invasive tumors possess the ability to degrade basement membrane. However, the presence of basement membrane may be affected not only by its degradation, but by its synthesis and deposition as well. Our results in the present study suggest that while the invasive human transitional carcinoma cell line EJ has an increased amount of type IV procollagen mRNA when compared to the non-invasive RT4 cell line, type IV collagen staining is absent in the invasive EJ cells and intensely present in the non-invasive RT4 cells. Moreover, when EJ cells were grown on an artificial basement membrane (Matrigel), type IV procollagen mRNA expression was down-regulated to the levels seen with the non-invasive RT4 cells. We also discovered that the invasive cells, when grown on Matrigel, appeared morphologically different from the same cells grown on plastic tissue cultures. We conclude that a deficient basement membrane in invasive cancer cells may be due not only to active proteolytic activity but also to an abnormal production and deposition of extracellular matrix components. In addition, we also demonstrated that basement membrane components may have a significant effect on epithelial cell morphology and gene regulation, and that any alterations of the extracellular matrix-cytoskeleton-nuclear matrix interactions can lead to altered gene regulations and cell function. PMID- 1856951 TI - Effects of sensitization on female guinea pig urinary bladder function: in vivo and in vitro studies. AB - Although bladder inflammation is known clinically to produce a variety of symptoms including urgency, frequency, and pain, there are only a few experimental studies that directly relate bladder inflammation with urodynamic and functional alterations. We have used the sensitized guinea pig model to study the effects of inflammation on micturition parameters, cystometry, and in vitro bladder contractility. This model depends on the allergic response of the bladder mucosa to ovalbumin, an otherwise non-irritative agent, as an antigen. In vivo exposure of the bladder to ovalbumin via urethral catheterization induced a prompt and marked increase in the number of micturitions in antigen-sensitized guinea pigs. Ovalbumin had no effects on the micturition parameters in the control group. Using in vivo cystometry, intravesical exposure to ovalbumin induced a significant decrease in both the pressure at which micturition was induced, and the volume at which micturition was induced. Ovalbumin had no effect on cystometric parameters of the control animals. In vitro exposure of whole bladder preparations to ovalbumin induced a significant contractile response only in the bladders isolated from the sensitized guinea pigs. The responses of the isolated bladders to field stimulation and bethanechol were identical for bladders from both sensitized and control animals. In conclusion, exposure of the bladder to ovalbumin in the sensitized animal induced an increase in the frequency of micturitions and a decrease in the pressure and volume at which micturition was induced. Thus, intravesical exposure of the bladder mucosa to a substance that the bladder has been sensitized to can induce alterations in micturition that are consistent with the clinical symptoms of "urgency and frequency". PMID- 1856950 TI - The possible influence of antibiotics on results of bacillus Calmette-Guerin intravesical therapy for superficial bladder cancer. AB - Intravesical treatment with Bacillus Calmette-Guerin is an established treatment of carcinoma in situ and an effective prophylaxis for the prevention of recurrence of transitional cell carcinoma. During instillation therapy oral antibiotics may be used to prevent or to treat urinary tract infections. Tuberculostatic agents are employed to prevent or to treat local irritative symptoms and systemic side effects caused by Bacillus Calmette-Guerin. We investigated the susceptibility of four different Bacillus Calmette-Guerin preparations to 18 antibiotics and to 11 tuberculostatic agents in vitro. All preparations were equally susceptible to most of the commonly used antibiotics and to all of the tuberculostatic agents with the exception of pyrazinamide. Our results suggest that in the absence of cystitis, instillations should not be accompanied by antibiotics because of the possible inhibition of antitumor efficacy by eradication of living Bacillus Calmette-Guerin organisms. The same inhibition may occur when tuberculostatic agents are used to prevent local and systemic complications of Bacillus Calmette-Guerin instillation therapy. PMID- 1856952 TI - Urease and the acidosis of urinary intestinal diversion. AB - Previous investigators have suggested that urinary tract infections with urea splitting organisms may be a primary etiologic factor in the acidosis which is seen after urinary diversion. This study employs a model in which small intestinal segments are perfused with an artificial urine solution over a three hour period. Urease is then added in order to determine its effect on acid-base balance and net intestinal electrolyte transport. Urease created no significant increase in acid load (delta HCO3- = -7.5 +/- 2.2 for controls vs. -8.7 +/- 2.9 for urease group), but did increase the osmolality of the intestinal contents and resulted in a 24% increase in free water loss (p = .037). Analysis of sodium and chloride movement following the addition of urease to the perfusate suggests that both ammonium and bicarbonate are absorbed by the intestinal segment. Thus any acidosis resulting from increased ammonium absorption following the addition of urease appears to be offset by concomitant bicarbonate absorption. The azotemia of urinary diversion appears to be primarily the result of urea absorption, partially the result of ammonium absorption, and is not significantly increased by urease. PMID- 1856954 TI - An immunochemical and immunohistochemical study of aldolase isozymes in renal cell carcinoma. AB - To assess changes in aldolase isozyme patterns (A, B, and C) in renal cell carcinoma (RCC) tissues and to evaluate whether serum aldolase A might be a useful marker for RCC, quantitative analysis by enzyme immunoassay and immunohistochemical localization were performed. Concentrations of aldolase A in RCC (7300 +/- 6300 ng./mg. protein n = 26) were significantly higher than those of normal cortex (720 +/- 410 ng./mg. protein, n = 14, p less than 0.01); concentrations of aldolase C in RCC (48.0 +/- 8.0 ng./mg. protein) were also significantly higher than those of normal cortex (8.7 +/- 4.7 ng./mg. protein, p less than 0.01). On the other hand, concentrations of aldolase B in normal cortex were 18,100 +/- 10,100 ng./mg. protein (n = 14), whereas the values in RCC were only 130 +/- 270 ng./mg. protein, a significant lowering (p less than 0.01). Immunohistochemically, aldolases A and C were found localized in all RCC tissues (n = 10); aldolase B was faintly stained in only a few tumor cells of two cases (20%). Levels of serum aldolase A were elevated (greater than 300 ng./ml.) in 30 (75%) of 40 patients with RCC as compared to three (6.3%) of 48 individuals with urogenital benign diseases and in seven (21%) of 34 cases with non-RCC urogenital malignancies. Since it is generally accepted that RCC are derived from renal proximal tubules, these findings indicate that aldolase B, the predominant isozyme in the normal case, changes into aldolases A and C during carcinogenesis and that serum aldolase A could be a new useful biomarker for RCC. PMID- 1856955 TI - Injury to the pre-pubertal vas deferens. I. Histological analysis of pre-pubertal human vas. AB - There is very little information in the literature on the development of the human vas deferens. Therefore, the age at which the pre- or para-pubertal vas deferens becomes large enough for a vasovasostomy to be technically feasible is unknown. To determine the age or degree of sexual maturity at which a microscopic vasovasostomy is technically feasible, we collected surgical or autopsy vasa from 34 young males over a three year period, and correlated vasal size to age and Tanner stage (degree of sexual maturity ranging from 1-childhood to 5-adult). The specimens were embedded and sectioned transversely in glycol methacrylate. Using image analysis, the total transverse area and diameter, and luminal area and diameter was determined for each specimen. Surprisingly, there was no change in vasal size from birth up through 11 years. From age 15 years and on, the vas was adult in size. The vas develops to adult size between Tanner stages 2 and 3. The average external and luminal diameters of pre-midpuberty specimens (Tanner stages 1 and 2) were 1.0 and 0.19 (mm.) and the diameters of post-midpuberty specimens were 2.1 and 0.43 (mm.), respectively. These results suggest that, in the event of a recognized iatrogenic injury to the vas deferens after midpuberty, a repair by a traditional microsurgical vasovasostomy is possible. If the vas is injured before midpuberty it may be technically difficult to repair by traditional microsurgical methods. PMID- 1856953 TI - Nerve growth factor, nerve grafts and amniotic membrane grafts restore erectile function in rats. AB - In an effort to reduce complications arising from radical pelvic surgery, an improved technique for restoration of autonomic innervation has been developed. The ability of nerve growth factor (NGF) alone or in combination with interposition nerve grafts, as well as the use of fetal amniotic membrane as an alternative growth matrix to enhance regeneration of ablated cavernous nerves were investigated in rats. Rats with ablated cavernous nerve displayed little or no penile erection, either in response to direct electrical stimulation or to an estrous female rat. A step wise improvement in electrically induced erections was observed by NGF alone, nerve graft alone, and the combination of NGF and nerve graft. Restoration of sexual behavior followed the same pattern obtained with electrical stimulation. Furthermore, the use of neonatal amniotic membrane as an alternative nerve growth matrix enhanced both electrically stimulated erection and mating behavior. These results suggest that the use of NGF and appropriate grafting materials can facilitate autonomic nerve regrowth and potentially reduce the morbidity of surgically induced nerve injuries. PMID- 1856956 TI - Injury to the pre-pubertal vas deferens. II. Experimental repair. AB - We have previously shown that the human vas deferens does not change in cross sectional size between birth and the middle of puberty. This suggests that if the human vas is injured prior to mid-puberty, repair by a traditional microsurgical vasovasostomy may be technically difficult. We propose that a chromic stent can be used to assist in the repair of vas injured before mid-puberty. This hypothesis was tested in Sprague-Dawley rats. At three weeks of age, male offspring were divided into three groups (eight to nine rats/group): 1) Sham group--a sham operation at three weeks, 2) VV group--bilateral transection of vasa at three weeks followed by a delayed repair at eight weeks by microsurgical vasovasostomy without a stent, 3) Stent group--bilateral transection of vasa at three weeks followed by immediate repair by aligning the lumens with a 6-0 chromic intravasal stent (suture) and holding the transected ends together with several seromuscular sutures. At four months all rats were fertility tested and a score was given to each rat (mean number of concepti among three females for each male rat). Analysis of anastomotic patency by flow rates and histology was performed. There was no statistical difference in the mean fertility score of 6.85 in the Stent group compared to 7.83 in the Sham group. However, a fertility score of 0.71 in the VV group was significantly decreased compared to the Stent and Sham group (p = .0003), despite no statistical difference between the groups in patency. This suggests that a recognized injury to the pre-pubertal human vas should be immediately repaired and the repair can be done using 6-0 chromic suture as an intravasal stent to help align the lumina of the smaller pre pubertal vas. PMID- 1856957 TI - Changes in bladder function in the one year spontaneously diabetic BB rat. AB - Micturition characteristics and in vitro urinary bladder function were investigated in insulin-treated spontaneously diabetic BB rats and age-matched non-diabetic controls one year after the onset of diabetes. BB rats weighed less than controls and were hyperglycemic. Diabetic rats consumed larger volumes of water and excreted larger volumes of urine than controls. The frequency of micturitions and the mean volumes of urine excreted per micturition were significantly increased in BB rats compared to age-matched controls. Associated with the micturition changes in the BB rats were significant increases in bladder body mass. Contractile responses of strips from bladder bodies and bases were measured in response to nerve stimulation, carbachol, phenylephrine, ATP, and KCl. No significant differences between controls and diabetics were found in the absolute contractile responses of bladder body strips to nerve stimulation, carbachol, ATP, or KCl. However, if the data were transformed to correct for the increases in tissue mass in the diabetics, there were significant decreases in the responses of bladder body strips from BB rats to carbachol, ATP, and KCl, but not to nerve stimulation. Even after transformation, there were no differences in the responses of bladder base strips to carbachol, phenylephrine, or KCl. The data indicate that significant changes in micturition characteristics are evident one year after the onset of diabetes in the spontaneously diabetic BB rat. These changes are slow in development, since they are absent six months after the onset of diabetes. The changes in micturition and bladder strip contractility are qualitatively similar to, but quantitatively modest in comparison with those caused by streptozotocin-induced diabetes mellitus. The quantitative differences are probably attributable to an ameliorative effect of the insulin received by the BB rat. PMID- 1856960 TI - [Guidelines for transfusion therapy]. PMID- 1856959 TI - [Changes of the functions and activities of blood components--red blood cells, platelets and coagulation factors--during storage]. PMID- 1856958 TI - Chinese medicinal herbs reverse macrophage suppression induced by urological tumors. AB - Tumors are known to produce factors suppressing macrophage function. In this study we demonstrated in vitro suppression of macrophage chemiluminescent oxidative burst associated with viable cells and cell-free extracts of two urological neoplasms--murine renal cell carcinoma (Renca) and murine bladder tumor (MBT). Suppression was reversed by extracts of two Chinese medicinal herbs, Astragalus membranaceus (AM) and Ligustrum lucidum (LL). Murine macrophage cell line J774 was incubated with either the viable tumor cells or the cell-free tumor extract for 18 hours at 37C and 5% CO2. Chemiluminescent oxidative burst as an indicator of macrophage function was triggered by adding zymosan A suspension containing luminol and assayed in an automated luminometer. Photon emission over time was counted and the results were expressed as integrated photon emission. Significant dose-related depression of oxidative burst occurred with either the viable tumor cells or the cell-free tumor extracts. Depression was partially or completely reversed by the presence of 50-100 micrograms./ml. of either the AM or the LL extract. AM and LL have previously been shown to modulate immune response. Data from this study suggest that they may also exert their antitumor activity via abolition of tumor-associated macrophage suppression. PMID- 1856961 TI - [Background and outline of the guideline for good practice of transfusion therapy]. PMID- 1856962 TI - [Practical manual of blood transfusion in nursing settings]. PMID- 1856963 TI - [Practical manual of blood transfusion in operation rooms and intensive care units]. PMID- 1856965 TI - [Transfusion associated graft versus host disease]. PMID- 1856964 TI - [Strategies for prevention of adverse transfusion effects. Immediate and delayed transfusion effects: laboratory reference for transfusion reactions]. PMID- 1856966 TI - [HTLV-I transmission by blood transfusion]. PMID- 1856968 TI - [Strategies and management of hospital blood center services for safety and efficacy of blood transfusion]. PMID- 1856969 TI - [Rationalization of the use of blood and blood preparations]. PMID- 1856967 TI - [Blood transfusion and HIV infection. Current status in the world and Japan]. PMID- 1856971 TI - [Current usage of blood products in Tokyo Metropolitan Komagome Hospital]. PMID- 1856970 TI - [Current status of organization of blood transfusion therapy in USA]. PMID- 1856972 TI - [The history of the usage of blood products in Kurashiki Central Hospital]. PMID- 1856973 TI - [Indication of in house blood donation during operations of patients with liver diseases]. PMID- 1856974 TI - [Indication for transfusion of preserved autologous blood in elective open heart surgery]. PMID- 1856976 TI - [Obstetrical hemorrhage]. PMID- 1856975 TI - [Blood donation in a hospital for transfusion in hematological diseases]. PMID- 1856977 TI - [Donor reactions to blood donations]. PMID- 1856978 TI - [Standards for preoperative autologous blood donation and preservation]. PMID- 1856979 TI - [Present and future of preservation of autologous blood set aside in a liquid state]. PMID- 1856980 TI - [Autologous blood transfusion at now and future: blood stored under frozen conditions]. PMID- 1856981 TI - [Informed consent for blood transfusion]. PMID- 1856982 TI - [Autotransfusion--a hemodilutional method]. PMID- 1856983 TI - [Autotransfusion--a salvaging method]. PMID- 1856984 TI - [Evaluation of the guideline for a good practice of transfusion therapy]. PMID- 1856986 TI - [Expectations on the guideline for blood transfusion. 2]. PMID- 1856985 TI - [Expectations on the guideline for blood transfusion. 1]. PMID- 1856987 TI - [Expectations on the guideline for blood transfusion. 3]. PMID- 1856988 TI - [Guidelines for appropriate transfusion therapy: a discussion]. PMID- 1856989 TI - [Report on a survey conducted among committee members of the Japanese Society of Blood Transfusion concerning the "Guideline for Transfusion Therapy"]. PMID- 1856990 TI - [Present status and the future of transfusion therapy in Japan]. PMID- 1856992 TI - [Guidelines for appropriate blood transfusion therapy: reference data]. PMID- 1856993 TI - [Guidelines for selection of blood donors in Japanese Red Cross Blood Center]. PMID- 1856991 TI - [Present status of the use of fresh whole blood]. PMID- 1856994 TI - [Report by the Subcommittee for the Appropriate Use of Blood Preparations]. PMID- 1856995 TI - [Blood grouping and crossmatching]. PMID- 1856996 TI - [Preparation and storage of blood products]. PMID- 1856997 TI - [Salivary epidermal growth factor in patients with peptic ulcer]. AB - Recent animal studies suggest salivary epidermal growth factor (EGF) has a cytoprotective effect in the upper GI tract and is one of the important factors to promote the healing of experimental ulcer. The present study was undertaken to clarify the role of salivary EGF in peptic ulcer patients. Saliva samples were collected from 129 endoscopically normal subjects and 232 peptic ulcer patients. Salivary EGF concentration was measured by RIA. Salivary EGF output in normal subjects was 5.26 +/- 0.26 (ng/5 min) (mean +/- SE). Those in patients with gastric ulcer (GU), duodenal ulcer (DU) and gastroduodenal ulcer (GDU) were 10.74 +/- 0.15, 8.13 +/- 0.83 and 9.79 +/- 0.91. EGF output in GU and GDU patients were higher than that in normal subjects respectively. Tractable GU patients (healed within 3 months with regular regimen) had higher EGF output than intractable GU patients. Among tractable GU patients, those who had healing within 8 weeks had higher output. EGF output in patients with recurrent GU was lower than that in non-recurrent GU patients. In 10 GU patients, EGF output became higher in healing stage than in active stage. Salivary EGF may promote the healing and prevent the recurrence of human gastric ulcer. PMID- 1856998 TI - [Dysplasia in ulcerative colitis detected by surveillance colonoscopy]. AB - A total of 222 surveillance colonoscopies were performed in 84 patients with ulcerative colitis between 1979-1989. In 60 patients with total colitis, 3 carcinomas, 2 high-grade, 4 low-grade and 8 indefinite for dysplasia were found. In 24 with left-sided colitis, 1 low-grade and 1 indefinite for dysplasia were found. The overall incidence of dysplasia in patients with total colitis was 28%, similar to the reported incidence from the Western countries. A sequence of dysplasia development was recorded in 14 cases. Progression of dysplasia was found in some of the low-grade or indefinite cases, however regression was also recorded in another cases. These results suggest the usefulness of surveillance colonoscopy for early detection of carcinoma in long-standing ulcerative colitis. PMID- 1857000 TI - [Clinical study of vitamin E status in patients with chronic liver diseases]. AB - Vitamin E status was evaluated in patients with chronic liver diseases (chronic hepatitis, CH; n = 27 and liver cirrhosis, LC; n = 32) by the ratio of plasma alpha-tocopherol to plasma lipids (P-toc/lipid) and red blood cell alpha tocopherol (RBC-toc). P-toc/lipid and RBC-Toc were significantly reduced in LC patients compared to controls (n = 31). There was a significant correlation between P-Toc/lipid and RBC-Toc values. Low vitamin E status was found in 3 patients with CH (11.1%) and 12 patients with LC (37.5%), but their P-Toc values were not necessarily reduced. Serum beta-lipoprotein concentration (beta-lipo) did not differ significantly between the low vitamin E group and the normal vitamin E group, but the ratio of P-Toc to beta-lipo was significantly reduced in the low vitamin E group. No significant differences were found in the clinical features or liver functions tests including parameters of hepatic synthetic functions and cholestasis between the two groups. Factors other than a cholestasis or an impaired synthesis of carrier protein may also be responsible for the frequent occurrence of low vitamin E status in patients with LC. PMID- 1856999 TI - [Increased polyamine levels of normal-appearing mucosa and cancers in DMH induced cancer-bearing colon in rats]. AB - Polyamine levels (putrescine, spermidine, spermine) in normal-appearing colonic mucosa of DMH administrated rats were measured in order to assess their importance as markers of precancerous changes. Mean putrescine, spermidine and spermine levels of normal-appearing mucosa were more than three times mean putrescine, more than twice mean spermidine and more than 1.5 times mean spermine levels of normal colonic mucosa. Mean polyamine levels of colon cancers were higher than those of normal-appearing mucosa but only spermidine level was significantly different between them. The mucosal polyamine levels may be a good biochemical marker to detect precancerous changes. There was no correlation between the polyamine levels and the growth rate of the colon cancers. PMID- 1857001 TI - [Abnormal prothrombin in acute hepatic failure: the characterization and clinical evaluation]. AB - Abnormal prothrombin was detected by latex agglutination method in the plasma of the patients with acute hepatic failure (AHF) at significantly higher rate (82% of fulminant hepatitis and 100% of subacute hepatitis) than in acute hepatitis (33%). The concentration of abnormal prothrombin was also significantly higher in acute hepatic failure. Since the concentration of abnormal prothrombin reversely correlated with that of hepaplastin test or prothrombin time, the measurement of plasma abnormal prothrombin seemed to be useful in monitoring the severity of acute hepatic injury. Interestingly, enzyme immunoassay which is specific for des gamma-carboxy prothrombin (PIVKA-II) could not detect abnormal prothrombin in acute hepatic failure. Furthermore, in crossed immune-electrophoresis, the abnormal prothrombin in AHF and that in disseminated intravascular coagulation syndrome showed similar mobility differing from PIVKA-II. These results suggest that abnormal prothrombin can be a useful marker for AHF. Further characterization of the abnormal prothrombin may shed light on the mechanisms of severe coagulopathy in AHF. PMID- 1857002 TI - [Cell kinetic studies on the gallbladder epithelium in patient with anomalous arrangement of pancreatobiliary duct]. AB - It is well known that the patients with anomalous arrangement of pancreatobiliary duct (AAPBD) are combined with biliary tract cancer. To clarify possible carcinogenesis of the gallbladder with AAPBD, DNA analysis of the gallbladder epithelium was performed in control (9 cases), AAPBD (26), gallbladder cancer confined in mucosa (10) and noncancerous epithelium around the gallbladder cancer (21). The mean values of DNA score, as already reported by us as an indicator of cell kinetics, were 12.1 (control), 27.2 (AAPBD, Type a), 13.3 (AAPBD, Type b), 14.8 (noncancerous epithelium around cancer) and 77.2 (gallbladder cancer confined in mucosa). The values of DNA score in the epithelium of AAPBD (Type a) showed significantly high level, which was next to that of cancer. Type a AAPBD may be supposed to have potential malignancy because of its accelerated cell cycle. But as Type b AAPBD without accelerated cell cycle combines cancer at least as often as Type a, further studies should be performed to reveal the relationship between cell cycle and malignancy. PMID- 1857003 TI - [Effects of CR1505, a CCK antagonist, on pancreatic growth in hamsters]. AB - The effects of CR1505, a CCK antagonist, on CCK-stimulated and normal pancreas were studied in Syrian golden hamsters. The CCK-stimulated trophic effect was inhibited by CR1505 in a dose-dependent manner, in which CR1505 100 mg/kg bw resulted in a complete inhibition of the weight of pancreas, the total pancreatic protein and DNA contents, compared to the control. Otherwise, CR1505 administration in doses of 25, 50, 100 mg/kg bw alone, didn't induce any significant changes among CR1505-treated groups and the control one. However, in the dose of 200 mg/kg bw, the weight of pancreas, the total pancreatic protein and DNA contents were significantly lower than control levels, suggesting pancreatic atrophy in the hamster. It's concluded that CR1505 is an effective CCK receptor antagonist that could inhibit the CCK-induced pancreatic trophic effect. Furthermore, CR1505 administration to normal pancreas brought out pancreatic atrophy, indicating that CCK seems to play an important role in the maintenance of normal pancreatic growth in hamsters. PMID- 1857004 TI - [A case of Ancylostoma duodenale dubini infection diagnosed by endoscopic removal]. PMID- 1857005 TI - [A case of mucoepidermoid carcinoma of the intrahepatic bile duct]. PMID- 1857006 TI - [An autopsy case of malignant lymphoma with multiple nodular lesions in the cirrhotic liver]. PMID- 1857007 TI - [A family line of acute intermittent porphyria with decreased delta-ALA dehydratase activity in erythrocyte]. PMID- 1857009 TI - [A case of extrahepatic portal vein aneurysm with liver cirrhosis]. PMID- 1857010 TI - [Idiopathic duodenal obstruction resembling pure groove pancreatitis: a case report]. PMID- 1857008 TI - [Idiopathic portal hypertension associated with intrahepatic portal aneurysm and splenic artery aneurysm--a case report]. PMID- 1857011 TI - [Correlation between nocturnal gastric secretory test and intragastric pH monitoring]. PMID- 1857012 TI - [Effectiveness of a fibrin adhesive on the treatment of liver cyst-casereport]. PMID- 1857013 TI - [Comparative effects between cholecystokinin-releasing peptide and monitor peptide on cholecystokinin release and pancreatic exocrine secretion in conscious rats]. PMID- 1857014 TI - An update on thermosensitive neurons in the brain: from cellular biology to thermal and non-thermal homeostatic functions. AB - TS neurons in the brain, particularly in the POA, play a central role in thermoregulation, based on the good correlations between the activity of TS neurons and the thermoregulatory responses. Such relationships have been observed during (1) thermal (hypothalamic and peripheral) and (2) pharmacological (amines, neuropeptides, cytokines, and exogenous drugs) stimulations, (3) during modulation of neural inputs from extraPOA brain regions, and (4) during actual thermoregulatory responses. In vitro studies utilizing tissue slice preparations and dissociated cellular preparations have revealed some mechanisms of thermal transduction of central TS neurons, which are apparently endowed with the unique characteristics of thermosensitivity. The high degree of convergence of thermal signals from local and remote sites on TS neurons suggests that locally TS neurons in one site of CNS are connected to TS neurons in the other sites, thus forming neural networks of TS neurons within the brain and the spinal cord. The findings that 40-70% of POA TS neurons respond to divergent types of non-thermal homeostatic signals and have abundant mutual connections with divergent areas of brain (limbic system and association cortices) indicate that TS neurons may be involved in the coordination of thermal and non-thermal homeostatic functions controlled in the hypothalamus. PMID- 1857015 TI - Influences of lung mechanoreceptors and carotid chemoreceptors on the response of respiratory muscle activity to tracheal occlusion. AB - We examined the responses of respiratory muscle electromyograms (EMGs) from internal (IIC) and external intercostal (EIC) muscles and diaphragm (DIAP) to three successive occluded breaths in anesthetized spontaneously breathing rabbits. Both inspiratory and expiratory muscle EMGs progressively increased in the course of tracheal occlusion. An increase in these muscle EMGs was still observed after release of tracheal occlusion, but those effects were short lasting. In a separate series of experiments, for assessment of possible reflex effects involved, the responses of slowly adapting pulmonary stretch receptor (SAR), rapidly adapting pulmonary stretch receptor (RAR), and carotid chemoreceptor activities to tracheal occlusion lasting for three respiratory efforts were also examined. The inspiratory discharge of SARs decreased but the expiratory discharge of SARs increased during tracheal occlusion. Although carotid chemoreceptors increased their activity in the latency of 3-6s after the onset of tracheal occlusion, the activity of RARs was greatly reduced throughout the period of tracheal occlusion. A transient increase in both carotid chemoreceptors and RARs was still observed after release of tracheal occlusion. These results suggest that alterations of inspiratory and expiratory muscle EMGs produced by tracheal occlusion would appear to be mediated by the afferent inputs from lung mechanoreceptors and carotid chemoreceptors. PMID- 1857016 TI - Constrictor response of small pulmonary arteries to acute pulmonary hypertension during left atrial pressure elevation. AB - Acute elevations in left atrial pressure (LAP) were induced by altering the volume of air within a balloon inserted into the left atrium; the changes in internal diameter (ID) of small muscular pulmonary arteries (100-600 microns ID) in response to the associated rises of pulmonary arterial pressure (PAP) were measured using an X-ray TV system on the in vivo cat lung. When LAP was elevated to 14 +/- 1, 24 +/- 1, and 30 +/- 1 mmHg, PAP was increased to 21 +/- 1, 30 +/- 1, and 37 +/- 1 mmHg, respectively. With PAP ranging from 16 (control value) to 21 mmHg the ID did not dilate significantly. With PAP of 30-37 mmHg significant ID dilation occurred. The magnitude of the ID dilation (16%) with PAP of 37 mmHg, however, was significantly smaller than that (20%) with PAP of 30 mmHg despite the greater pressure rise. When the elevated PAP of 30-37 mmHg was quickly returned to the control level by rapid balloon deflation, the ID constricted significantly below the control level. The magnitude of the ID constriction was proportional to the degree of the preceding PAP rise and was maximal in the arteries of 200-400 microns ID. A papaverine hydrochloride injection combined with the balloon deflation completely abolished the ID constriction. A phentolamine injection, on the other hand, significantly attenuated the constriction with approximately half of the constriction persisting. The results indicate that an increase in vascular smooth muscle tone occurred in the small muscular pulmonary arteries, particularly those of 200-400 microns ID, in response to the acute rise of PAP above 30 mmHg during the LAP elevation. In addition, the data suggest the partial participation of catecholamines in the active contraction of vascular smooth muscle. The arterial contraction may serve to protect the pulmonary capillaries from an excessive hydrostatic pressure and pulmonary edema. PMID- 1857017 TI - Exercise mode affects muscle sympathetic nerve responsiveness. AB - To compare the responses of remote sympathetic nerves to dynamic and static leg exercises, we recorded sympathetic nerve activity leading to skeletal muscle (MSNA) using a tungsten microelectrode during one-leg cycling at loads of 0, 25, and 50 W and during static leg extension (SLE) at 20% of maximal voluntary contraction. Oxygen uptake (Douglas bag method) and local fatigue sensation (LFS) of the working muscle were measured during cycling and SLE. MSNA decreased from the control value, respectively, by 25, 21, and 12% during cycling at loads of 0, 25, and 50 W. The differences from the control value were significant except during cycling at 50 W. On the contrary, MSNA increased from the control value by 83% during SLE. Oxygen uptake during 25 and 50 W leg cycling was greater than during SLE, whereas LFS was higher during SLE than during leg cycling at any load. The results indicate that the response of muscle sympathetic nerves to exercise does not exclusively reflect whole body metabolism, but is instead related to the local metabolic changes. PMID- 1857018 TI - Dose effects of acetylcholine on the cell volume of rat mandibular salivary acini. AB - The effects of acetylcholine (ACh) on the cell volume of the isolated rat mandibular acini were studied stereologically using video-enhanced contrast optical microscopy. The lengths of major and minor axes of the acini were measured in the successive video images, from which the relative volume change was estimated. ACh induced a rapid shrinkage of the acinar cell to reach minimum volume within 1 min. Simultaneously, the acinus and acinar clump shrunk in the same proportion as the acinar cell. The initial volume decrease induced by ACh was dose dependent: 0.92 at 10(-8) M, 0.91 at 10(-6) M, 0.77 at 10(-5) M, 0.78 at 10(-4) M, and 0.75 at 10(-3) M (the relative volume compared with the resting control). During sustained stimulation by ACh for 3 min, the volume of acinar cell remained at the plateau level at concentrations lower than 10(-5) M ACh, whereas the volume increased by 0.1-0.15 at concentrations higher than 10(-4) M ACh. The dose-dependent manner of the cell volume coincided with the fluid secretion measured in the isolated perfused gland. The findings on the dose effects of ACh are discussed in connection with the intercellular communication and the movement of electrolytes. PMID- 1857019 TI - Somatic afferent regulation of plasma corticosterone in anesthetized rats. AB - Effects of cutaneous stimulation on plasma corticosterone were examined in adult male Wistar rats anesthetized with pentobarbital. Under the resting condition, plasma corticosterone measured every 15 min between 1430 and 1630 h revealed no significant circadian fluctuations. Nociceptive mechanical stimulation of bilateral hindpaws by pinching for 10 min significantly increased plasma corticosterone for the following 1 h, whereas innocuous mechanical stimulation of bilateral hindlimbs by brushing for 10 min produced no significant change in plasma corticosterone. These results indicate that somatic sensory information from skin can influence secretion of corticosterone from the adrenal cortex after emotional factors are eliminated by anesthetizing the subjects. PMID- 1857020 TI - Oxygen consumption in resting dog gracilis muscle perfused at varying oxygen delivery. AB - The different response of O2 uptake (VO2) of resting skeletal muscle to the changes in blood flow has been thought to reflect a species difference. To scrutinize this notion, we investigated the relation between O2 delivery (arterial O2 content multiplied by blood flow) and VO2 in isolated dog gracilis muscle perfused solely with normal hematocrit (Ht) blood (n = 9), or alternately with normal and low Ht blood (n = 6), or alternately with normal and high Ht blood (n = 3) at varying perfusion rates. Eleven out of the 18 preparations showed an autoregulation of blood flow, and the others did not. But, in all preparations, the VO2 was delivery-independent above a critical O2 delivery (0.45 ml/(min.100 g muscle)) and showed the constant VO2 of 0.30 ml/(min.100 g), while below the critical level it turned out to be delivery-dependent. The maximal extraction ratio was 0.67. The same relationship was found with the low and high Ht perfusion. The pattern observed in dog gracilis muscle was essentially the same as that in rat gracilis muscle (KOLAR and JANSKY, 1984). PMID- 1857021 TI - Optical measurement of perfused rat hindlimb muscle with relation of the oxygen metabolism. AB - Optical measurements of myoglobin (Mb) and cytochromes (Cyts) in the isolated rat hindlimb muscle perfused with cell-free medium were performed at 35 and 15 degrees C under various oxygen supply, in the relation to the oxygen metabolism. Molar ratio of Cyt a + a3, Cyt b, Cyt c + c1, and Mb, oxygen affinity of Mb (P50), and the thermodynamic parameter (delta H degree) of Mb oxygenation in cyanide-perfused muscle were similar to those reported. The "apparent P50" of Mb in cyanide-free muscle was almost two orders larger in magnitude than P50 in the presence of cyanide. O2 uptake by the perfused hindlimb muscle was constant above O2 supply of 0.73 mumol/(min.g muscle) (under a flow rate of 1.0 ml/(min.g muscle) at 35 degrees C). Below the value of O2 supply, the O2 uptake decreased and lactate/pyruvate ratio increased. The critical mean oxygen tension in tissue (estimated by Mb oxygenation) for O2 uptake at 35 degrees C was ca. 10 mmHg. It was found that oxidation level (%) of Cyt a + a3 was equivalent to oxygenation level (%) of Mb at 35 degrees C, while the oxidation level of Cyt a + a3 was higher than the oxygenation level of Mb at 15 degrees C. Based on the results, the uneven distribution of O2 in the muscle tissue and the intracellular O2 gradient were discussed. PMID- 1857022 TI - Changes in basal secretion rates of thyroxine and 3,3',5-triiodothyronine from the thyroid gland during aging of the rat. AB - The present experiments were carried out to examine age-related changes in the basal secretion rates of both thyroxine (T4) and 3,3',5-triiodothyronine (T3) from the thyroid gland. The experiments were performed on male Wistar rats of three different ages, i.e., (1) adult rats of 6-8 months old, (2) middle-aged rats of 25-26 months old, and (3) aged rats of 28-30 months old. The rats were anesthetized with 1.0% halothane. The thyroid venous blood as well as systemic arterial blood was collected and secretion rates of both immunoreactive T4 (iT4) and T3 (iT3) from the thyroid gland were calculated from the differences in concentrations of iT4 and iT3 in these two blood plasmas, and from the flow rate of thyroid venous blood plasma. The secretion rates of thyroid iT4 in the three different age groups were as follows: 483 +/- 68 pg/min (mean +/- S.E.) in the adult rats, 598 +/- 104 pg/min in the middle-aged rats, and 491 +/- 150 pg/min in the aged rats. There were no significant differences among the secretion rates of thyroid iT4 in these rats. The secretion rates of thyroid iT3 in the groups were as follows: 36.2 +/- 7.5 pg/min in the adult rats, 58.9 +/- 13.9 pg/min in the middle-aged rats, and 61.3 +/- 7.6 pg/min in the aged rats. The secretion rates of thyroid iT3 in both middle-aged and aged rats were approximately 1.6-1.7 times as high as the value in adult rats (p less than 0.05). These results indicate that the thyroid secretion of iT4 is well maintained, while that of iT3 increases during aging. PMID- 1857023 TI - Behavioral effects of adenosine agonists: evaluation by punishment, discrete shuttle avoidance and activity tests in mice. AB - Behavioral effects of propentofylline and N6-(L-2-phenylisopropyl)-adenosine (PIA) were evaluated by operant behavior under a punishment situation, discrete shuttle avoidance response and ambulatory activity in mice. Propentofylline (3 mg/kg, s.c.) and PIA (0.01 mg/kg, s.c.) significantly decreased the punished response without producing a significant change in the non-punished response. Propentofylline and PIA reduced the increase in the punished response induced by caffeine (30 mg/kg) and diazepam (1 mg/kg). Propentofylline and PIA also reduced the increase of ambulation induced by caffeine. Furthermore, the single administration of propentofylline and PIA decreased the response rate and/or % avoidance in the discrete shuttle avoidance situation. However, the effective doses of propentofylline and PIA to reduce the ambulation-increasing effect of caffeine and to produce a change in the avoidance behavior were much higher than those effective for eliciting a significant change in the punished response. The present results suggest that there is an intimate interaction between central adenosine and benzodiazepine systems with regards to the change of punished response. PMID- 1857024 TI - Guanosine 5'-triphosphate converts some populations of propylbenzilylcholine mustard-sensitive muscarinic cholinoceptor sites to sites resistant to the drug in intestinal smooth muscle. AB - From functional studies with propylbenzilylcholine mustard (PrBCM), we reported that there coexist PrBCM-sensitive and PrBCM-resistant muscarinic cholinoceptor mechanisms in guinea pig taenia caecum. We investigated the interrelationship between these two cholinoceptor mechanisms using an in vitro receptor binding assay with [3H]quinuclidinyl benzilate (QNB) and [3H]PrBCM. Pretreatment of the muscle strips with 300 nM PrBCM (in vivo alkylation) for 10-50 min resulted in progressive decreases of the number of the maximum [3H]QNB binding sites. However, a prolongation of the period of in vivo alkylation up to 90 min was accompanied with no further loss in the binding sites. Under these conditions, there is no significant change in the affinity of [3H]QNB for the binding sites. The concentration of carbachol required to displace 50% of the bound [3H]QNB was larger in membranes obtained from the tissues that had been alkylated in vivo with PrBCM for 50 min than that from control strips, but was not altered when the pretreatment with the drug was carried out after homogenization (in vitro alkylation). When GTP was added during in vitro alkylation, the affinity of carbachol was lower than that in control membranes, as observed when in vivo alkylation was carried out. In the presence of guanine nucleotide, PrBCM thus appears to recognize two distinct populations or states of muscarinic receptors. PMID- 1857025 TI - Ryanodine suppresses the frequency-dependent component of the spike after hyperpolarization in the rat superior cervical ganglion. AB - The spike after-hyperpolarization (AH), which is linked to the Ca-activated K conductance system, in the rat superior cervical ganglion was examined by means of intracellular recording. The AH was shortened during repetitive stimulation of the cell at 1 Hz and reached a steady state within 10 sec. These changes in the AH disappeared after a part of the AH was depressed by 5 microM ryanodine. The steady state of AHs was dependent on the frequency of stimulation ranging from 0.005 Hz and 2 Hz: half depression was observed at 0.53 Hz. Half recovery time from the depression induced by conditioning stimuli at 2 Hz was approximately 14 sec. Caffeine (1 mM) or TEA (3 mM) enlarged the AH at low stimulation frequencies. Caffeine slightly shifted the frequency depressing the AH toward high frequencies, and TEA did not cause significant changes. These results suggest that the repetitive firing of cells decreases the intracellular Ca release by contributing to the generation of the AH, rather than by accelerating the loading of Ca to its storage sites. PMID- 1857026 TI - Effects of indomethacin, endothelium-denudation, methylene blue and L-NG monomethyl arginine on the vasoactive effects of endothelin-3. AB - To clarify the mechanisms underlying the vasoactive effects of endothelin-3 (ET 3), we examined the effects of indomethacin, endothelium-denudation, methylene blue and L-NG-monomethyl arginine (L-NMMA) on the perfusion pressures of isolated rat mesenteric arteries infused with ET-3. ET-3 at 10(-15)-10(-8) M elicited significant vasodilations in a dose-related manner, in which 10(-9) and 10(-8) M ET-3 caused biphasic pressure changes involving a transient dilation and subsequent vasoconstriction. Five micromolar indomethacin did not affect the vasodilations and vasoconstrictions induced by ET-3. In endothelium-denuded arteries, 10(-13)-10(-8) M ET-3 elicited significant vasoconstriction in a dose related manner without any vasodilation. In the presence of 30 microM methylene blue, the vasodilations induced by ET-3 disappeared. In the presence of 100 microM L-NMMA, 10(-15)-10(-8) M ET-3 elicited significant vasoconstrictions in a dose-related manner, and the vasodilation by ET-3 existed only at 10(-8) M ET-3. These data suggest that the vasodilating effects of low doses of ET-3 through the endothelium overcome the vasoconstricting effects, and that the vasodilating effects of ET-3 are associated with an endothelium-derived relaxing factor as an endothelium-derived nitric oxide. PMID- 1857027 TI - Differential intracardiac sympathetic and parasympathetic innervation to the SA and AV nodes in anesthetized dog hearts. AB - Stimulation of discrete intracardiac sympathetic nerves to the SA (SAS stimulation) or AV nodal region (AVS stimulation) increased the heart rate or decreased AV conduction time and caused an AV junctional rhythm, respectively, in anesthetized dogs treated with atropine. Topical application of tetrodotoxin (TTX) at the SAS or AVS stimulation locus totally inhibited the response to each stimulation, whereas each TTX treatment slightly attenuated the chronotropic response to the right ansa stimulation by 23 +/- 7.7% and the dromotropic response to the left ansa stimulation by 7 +/- 7.5%. TTX abolished AVS stimulation-induced one. Before atropine, topical application of hexamethonium at the locus for stimulation of intracardiac parasympathetic nerves to the SA (SAP stimulation) or AV nodal region (AVP stimulation) abolished almost totally negative chronotropic responses to SAP and cervical vagus stimulation or negative dromotropic responses to AVP and cervical vagus stimulation, respectively. These results demonstrate that activation of a very small population of intracardiac sympathetic nerves to target cells is enough to induced positive chronotropic and dromotropic responses in the heart in situ, and that SA and AV nodal pacemaker activity and AV conductivity are controlled multi-directionally by intracardiac sympathetic nerves in contrast with parasympathetic ones. PMID- 1857028 TI - Effects of L-tryptophan on the development of tolerance to the antitussive effects of dihydrocodeine. AB - The effects of L-tryptophan on the development of tolerance to the antitussive effects of dihydrocodeine were examined in rats. Chronic co-administration of L tryptophan with dihydrocodeine prevented the development of tolerance to the antitussive effects of dihydrocodeine. Furthermore, the antitussive effects of dihydrocodeine in dihydrocodeine-tolerant rats were fully restored by acute co administration of L-tryptophan, as evidenced by a decrease of about 50% in the ED50 value of dihydrocodeine. Thus, it is concluded that L-tryptophan may antagonized the development of tolerance to the antitussive effects of dihydrocodeine. PMID- 1857030 TI - The results and problems of extensive radical surgery for carcinoma of the head of the pancreas. AB - Since 1973, 152 patients with pancreatic carcinoma have undergone surgery in our clinic, including 110 with carcinoma of the head of the pancreas. Of these 110 patients, resections were performed on 43 (39.1 per cent), 33 (30 per cent) of whom underwent a curative resection based on macroscopic evidence. Six of the patients who underwent macroscopic curative resection survived for five years, giving a five-year survival rate of 36.5 per cent by the Kaplan-Meier method after excepting 6 operative deaths. We compared the extent of pancreatic cancer by constructing survival curves according to the General Rules published by the Japan Pancreas Society. There was no statistical difference in survival based on tumor size or stage, however, there was a significant difference in the survival curves of so and se, being the absence or presence of the anterior capsule of the pancreas, rpo and rpe, being the absence or presence of invasion of the retroperitoneal tissue; ew(-) and ew(+) being the absence or presence of invasion at the surgical margin of resection, or n0 and n1 being the extent of lymph node metastasis. The results of this comparison suggest that extended radical pancreatectomy may be indicated for the treatment of pancreatic cancer as the standard radical operation for pancreatic cancer may miss tumors which have spread to the retroperitoneum and extrapancreatic nerve plexus. PMID- 1857031 TI - The formation of gastric ulcers with a tendency to hemorrhage in association with aortic aneurysms. AB - It is widely accepted that patients with aortic aneurysm (AA) show a higher incidence of peptic ulcers than those without. However, the pathogenesis of peptic ulcers associated with AA remains obscure. We measured the gastric mucosal blood flow (GMBF) endoscopically and also determined the gastric mucosal prostaglandin (PG) levels of these AA patients to investigated the mechanism behind gastric ulcer formation. Moreover, we investigated the consumption coagulopathy (CC) of AA responsible for inducing the hemorrhage from ulcers. The GMBF values of 7 AA cases, taken at the antrum, angle and corpus, were significantly decreased compared with those of control cases, while the PGE2 levels of the gastric mucosa were also significantly reduced. With regard to CC, the serum levels of fibrinogen or platelets were significantly lower than those of the control group. These results indicate that the decrease in GMBF, followed by the reduction in endogenous PG, might contribute to the gastric ulcer formation in AA patients, and that CC associated with AA could be an important factor causing the hemorrhage from these ulcers. AA patients should therefore be treated with focusing attention on the possibility of an associated ulcer and ulcer bleeding. PMID- 1857029 TI - The clinical and biological significance of the transitional mucosa adjacent to colorectal cancer. AB - The underlying nature of the transitional mucosa adjacent to colorectal cancer is defined and the evidence for and against the statement that this transitional mucosa involves primary premalignant change presented in this article. An association between mucin histochemical changes at the margins of resection and a poorer clinical outcome of patients has been recognized in patients with colorectal cancer after surgery. The retained transitional mucosa at the margins of resection appears to correlate with tumor recurrence and a poorer survival in patients who have undergone radical resection. It is considered that the transitional mucosa adjacent to colorectal cancer and its presence at the margins of resection may be an important prognostic marker for patients with large bowel cancer following radical resection. PMID- 1857033 TI - Effects of the oral or intratumoral administration of OK432 on the immuno reactivities of regional lymph nodes in gastric cancer patients. AB - The effects of OK432, a streptococcal preparation, administered either orally (PO OK432) or intratumorally (IT-OK432) on the immuno-reactivities of regional lymph nodes were investigated in gastric cancer patients. Although native lymph node lymphocytes (LNL) from untreated patients did not show any cytotoxicities against K562 and Raji cells, enhanced activities were found in LNL from patients administered OK432. Augmenting effects on the cytotoxicities of LNL by in vitro additional OK432, interleukin 2 or gamma-interferon were remarkable in the patients given IT-OK432. Moreover, the cytotoxicities of peripheral blood lymphocytes were augmented in vitro more strongly in patients given IT-OK432 than in those given PO-OK432. Flow cytometric analysis of LNL revealed a decrease in CD4+ cells by PO-OK432 and an increase in CD8+ cells by IT-OK432. An increase in CD4+2H4+ cells and a decrease in CD4+2H4- cells were observed in the patients given OK432, though CD8+CD11+ cells decreased by PO-OK432 while CD8+CD11+ cells increased by IT-OK432. Thus, it is suggested that LNL reactive to OK432 immunotherapy may differ between PO- and IT-OK432, and that the immunoreactivities of local lymph nodes and systemical immuno-reactivities may be highly potentiated by IT-OK432 rather than PO-OK432. PMID- 1857032 TI - Generalized peritonitis in India--the tropical spectrum. AB - Generalized peritonitis is a common surgical emergency in India, the 'Tropical Spectrum' of generalized peritonitis being different from the western spectrum. A total 155 cases of generalized peritonitis were surgically treated at the All India Institute of Medical Sciences between 1981 and 1987, all patients undergoing peritoneal toilet with drainage after the cause of their peritonitis had been treated. The most common cause of peritonitis was peptic ulcer perforation, with simple closure being associated with a 2 per cent mortality, while typhoid perforation was the second most common cause. The diagnosis was clinical, supported by the operative findings of a terminal ileal perforation while bacteriological, serological and histopathological confirmation was retrospective. Appendicular perforations were less common than in the west but the clinical picture was the same. Tubercular perforations were not uncommon with a previous history of subacute intestinal obstruction and evidence of tuberculosis on chest X-ray suggesting the diagnosis. Ruptured amebic liver abscess was the most common hepatobiliary cause of generalized peritonitis with drainage of the abscess producing good results. The average hospital stay was 15 days with an overall mortality of 8 per cent. PMID- 1857034 TI - A hemodynamic study of the biventricular bypass total artificial heart with special reference to intrarenal flow distribution. AB - The present study was undertaken to determine whether a biventricular bypass total artificial heart driven in an independent variable rate mode can maintain circulation in vital organs such as the brain and kidney. Special emphasis was placed on investigating flow distribution. Two pusher-plate pumps were used to bypass the right and left ventricles in 11 goats and 12 sheep with fibrillating hearts. The carotid artery and renal artery flows were then measured using an ultrasonic blood flow meter and the regional renal blood flow calculated using the hydrogen gas clearance method. Thirteen animals were kept alive for 24 hours in physiological hemodynamics but 10 animals died of shock within 24 hours. In the latter group, a decrease in the fractional distribution of flow to the kidney and renal cortex were observed. At a peak aortic pressure of less than 100 mmHg, the renal flow ratio was significantly correlated with the peak aortic pressure. It was thus concluded that the biventricular bypass total artificial heart operated in an independent variable rate mode maintains physiological circulation and is therefore able to substitute for native heart function in any situation. PMID- 1857035 TI - Kinetic analysis of experimental post-operative peritoneal healing: the incorporation of proline and glucosamine by exudative and tissue repair cells. AB - The purpose of this study was to experimentally investigate the cellular composition of post-surgical peritoneal fluid and peritoneal tissue and determine the patterns of 14C-proline and 14C-glucosamine incorporation by the peritoneal exudative cells and peritoneal tissue repair cells (PEC and PTRC). One group of rabbits underwent resection (2.0 cm) and reanastomosis of their ileum, and another group underwent peritoneal wall abrasion. Postoperatively (1-28 days), the PEC and PTRC were collected and incubated for 5 days with 0.5 mu Ci 14C glucosamine or 14C-proline, and the specific activity thereafter determined by beta counting. On the 1st postoperative day, the total cell number (TCN) has increased (7.7 x 10(7) cells/rabbit) to 770 per cent of the control values primarily as a result of the PMN influx (89.9 per cent). On day 3, the TCN was 6.1 x 10(7), 58.5 per cent of which comprised macrophages, which had become the principle cell type by day 5. The incorporation of proline and glucosamine into the PEC increased significantly peaking on day 7 then decreasing to the control value by day 21. Proline incorporation into the PTRC increased significantly, reaching a peak value on day 5, which decreased by day 10. Glucosamine incorporation reached a peak value on day 7 then decreased by day 10. In conclusion, the increase in glucosamine and proline incorporation into the PTRC parallels the increase in PEC, comprised principally of macrophages. These findings suggest that analysis of the metabolic activities in peritoneal activated macrophages may provide a useful tool to dissect the central mediation of postsurgical peritoneal re-epithelialization. PMID- 1857036 TI - Segmental primary sclerosing cholangitis mimicking bile duct cancer--report of a case and review of the Japanese literature. AB - A rare case of the segmental type of primary sclerosing cholangitis (PSC) is reported herein. A 27 year old Japanese man with obstructive jaundice was referred to our hospital with a provisional diagnosis of bile duct cancer at the hepatic hilum. A PTCD tube had been inserted from the right anterior segmental duct and direct cholangiograms showed complete obstruction of the bile duct at the confluence of the right and left hepatic ducts. Resection of the extrahepatic bile duct and partial hepatectomy were thus performed, however, the postoperative histological examination revealed no malignant features. Instead, the lesion was shown to be compatible with PSC microscopically. A diagnosis of PSC was finally established on the basis of clinical features, cholangiographic appearance and the pathological report. PMID- 1857037 TI - A case of calcifying carcinoma of the stomach with long-term postoperative survival. AB - A 28 year old man suffering from calcifying carcinoma of the stomach underwent a gastrectomy which was histologically classified as being a noncurative resection. As postoperative adjuvant chemotherapy, he received 116 mg of Mitomycin C and 454.8 g of Tegafur as well as 5690 g of ascorbic acid. He showed carcinoma cells histologically at both oral and anal edges of the resected specimen, and peritoneal metastases of tumor cells were also observed, but he nevertheless kept a performance status of 1 until 5 years after surgery. The patient finally died of cachexia 5 years and 6 months after his operation. Among 42 patients with calcifying carcinoma of the stomach reported in the foreign literature and 19 patients reported in Japanese, those patients for whom the postoperative survival time was clearly indicated did not necessarily survive longer than those patients without calcification. PMID- 1857038 TI - Coombs-positive autoimmune hemolytic anemia in ulcerative colitis--a report of two cases. AB - Two cases of ulcerative colitis with a positive Coombs test are reported herein. In a 30 year old woman, hemolytic anemia was well controlled by excision of a rectal stump left over from a former operation. A 53 year old woman had a positive Coombs test without clinical hemolytic anemia 10 years after undergoing a total procto-colectomy with ileo-anal anastomosis. Thus we concluded that total procto-colectomy may be preventive, as well as therapeutic, for Coombs positive hemolytic anemia associated with ulcerative colitis. PMID- 1857039 TI - Surgical treatment of a huge hepatic artery aneurysm--a case report. AB - A debilitated 68 year old woman with an epigastric mass previously identified as a hepatic artery aneurysm (HAA) by selective angiography, developed acute epigastric pain radiating to her back. Impending rupture was diagnosed, and the patient successfully underwent surgical repair using a prosthetic patch to close the orifice of the aneurysm. HAA is uncommon, but the risk of rupture is great, being 44 per cent and the mortality rate high, being 35 per cent. Abnormal ultrasonography and CT may suggest the diagnosis, but selective arteriography is definitive. Surgical treatment is indicated in most patients, although embolization is appropriate for intrahepatic aneurysm and extremely poor risk patients. PMID- 1857040 TI - Liver abscess as the initial manifestation of colonic Crohn's disease: report of a case. AB - Liver abscess is a rare complication of Crohn's disease and in most of the reported cases, the diagnosis of Crohn's disease preceded that of liver abscess. We report herein a case in which a liver abscess was the initial clinical manifestation of Crohn's disease in a 36 year old man who presented with high fever and weakness. The diagnosis of liver abscess was established by abdominal ultrasonography, computed tomography and an arterial blood culture. The abscess was resolved with antibiotic therapy alone and during the drug therapy, a barium enema examination was performed which revealed a stricture at the transverse colon. Resection of the transverse colon was performed and macroscopic and microscopic examination of the resected specimen established the diagnosis of Crohn's disease. The liver abscess was thus speculated to be secondary to the inflamed bowel. Although rare, Crohn's disease should be included in the differential diagnosis of diseases causing liver abscess. PMID- 1857041 TI - Metastasis of cancer to cancer: report of a case of esophageal carcinoma metastasizing to early gastric cancer. AB - A rare case of esophageal carcinoma metastasizing to early gastric cancer is reported herein. A 66 year old man who had experienced dysphagia for 8 months was preoperatively diagnosed as simultaneously having esophageal and gastric cancers. Thus, a lower esophagectomy and total gastrectomy with paraesophageal and paragastric lymph node dissection were performed. The surgical specimen revealed an ulcerative tumor in the lower esophagus and a slightly depressed lesion with a central elevation similar to that of early type IIc + IIa gastric cancer in the upper part of the stomach. Microscopically, the esophageal tumor was revealed to be well differentiated squamous cell carcinoma while the gastric tumor was found to be early gastric cancer with a metastatic focus of esophageal cancer in the center. Though less than one hundred cases of metastasis of cancer to cancer have previously been reported, metastasis from cancer of one digestive organ to that of another digestive organ is very rare. To our knowledge, this report represents the first case of an esophageal carcinoma metastasizing to a gastric carcinoma. PMID- 1857042 TI - Frank melena in a patient with fallopian tube pregnancy. AB - We present herein a case of a young woman who experienced lower intestinal hemorrhage caused by ischemic necrosis of the small intestine induced by the compression of a Fallopian tube hematoma in an ectopic pregnancy. All accessible preoperative attempts to clear the site of the bleeding were unsuccessful and an exploratory laparotomy was indicated seventeen days after the development of melena. An ileocecal resection and right salpingectomy finally had to be performed. PMID- 1857043 TI - Giant extrathoracic hematoma after thoracoplasty--a case report. AB - A rare case of an extrathoracic giant hematoma developing after a thoracoplasty in a 67 year old man is presented herein. The patient underwent a right thoracoplasty without removal of plombage and a left thoracoplasty with removal of plombage for tuberculosis of the bilateral upper lobes 27 and 24 years prior to presentation, respectively. He presented to us in May, 1987, with a subscapular tumor which had been growing over the last 5 years. A giant tumor, measuring 23 x 17 x 12 cm and weighing 2585 g was successfully removed and the patient has since been well without any evidence of recurrence. PMID- 1857044 TI - [Kawasaki syndrome in infants in the first 6 months of life]. AB - Diagnosis in Kawasaki disease usually is made on the so called main symptoms and on laboratory findings. The analysis of three cases in the first six months of life demonstrated that the typical symptoms concerning the mucosa and the lymphatic nodes are rare in this age group, whereas drug resistant fever and polymorphic exanthema was present in all patients. Besides that accessory symptoms like abacterial meningitis and pathologic urine analysis seemed to be frequent signs. Laboratory findings such as pathologic blood sedimentation rate, elevated CRP and thrombocytosis on the other hand were helpful in making the diagnosis. PMID- 1857045 TI - [Congenital pulmonary vein stenosis as a rare cause of pulmonary hypertension]. AB - We report on the history, the diagnostic, and the operative procedure in an infant with congenital stenosis of all pulmonary veins. First symptoms such as failure to thrive, tachydyspnea, tachycardia and hepatomegaly occurred in the eighth week of life. Electrocardiography, 2-dimensional echocardiography and radiography of the chest were unspecific. After recurrent episodes of pulmonary oedema cardiac catheterization was performed: bilaterally elevated pulmonary artery wedge pressure and a normal left atrial pressure proved pulmonary venous obstruction. Severe stenosis of all pulmonary veins was apparent cineangiographically only by selective injections into the right and left pulmonary artery branches in wedge position. The operation (excision of the stenotic area and reimplantation using autologous pericardium) was unsuccessful as in most cases described in the literature. Congenital stenosis of all pulmonary veins is a rapidly progressive malformation. Death occurs usually in the first year of life with and without operation. PMID- 1857046 TI - [Trans-catheter closure of patent ductus arteriosus in childhood--an alternative to surgical ligature]. AB - Transcatheter closure of a persistently patent ductus arteriosus (PDA) was successfully performed in four children using a Rashkind double disk umbrella device. Mean age was 5.1 +/- 1.5 (2.8 to 6.3 years) and weight 18.8 +/- 3.8 kg (14.1 to 22.3 kg). In all children the PDA was the only cardiac lesion and was diagnosed clinically and by means of continuous wave and color-coded doppler echocardiography. After angiographic measurement of PDA size the correlating device was implanted. The ductus was closed immediately in two children, whereas there was a residual angiographic shunt in the others. Echocardiography performed within 24 hours showed a minimal shunt only in one of these cases. The shunt had disappeared at the one month follow up study. We experienced none of the reported possible complications. Transcatheter closure of the PDA after the neonatal period seems to be a safe and effective alternative to surgical ligation as our early experience shows, and should become the procedure of first choice in these patients. PMID- 1857048 TI - [Secretory immunoglobulin A in saliva of healthy children and children with airway diseases]. AB - Using the Elisa-Test of Dakopatts, Hamburg, described by Ishiguro et al and modified by us (Mikrotitration plates instead of tubes, blocking up free bonding capacities in the plates with 1% gel fluid, altered incubation periods) we determined secretory IgA (SIgA) in saliva samples of 376 infants and children. The probands could be divided in three groups: Group 1, serving as controls, consisted of 163 healthy children. Group 2 comprised 111 children suffering from acute infection of the respiratory tract. Group 3 consisted of 102 children with chronic airways diseases, in particular, asthma. In the healthy infants and children we found age dependent increases of SIgA until the age of 4 years. The median values amounted 16.7 (newborns), 59.2 (1st year), 118.2 (2nd year), 149.2 (3rd year), 185.5 (4th year), 159 (5th year) and 175.8 mg/l (5th-13th year). A similar age dependent increase of SIgA was evident in the saliva samples of children suffering from acute infections of the respiratory tract. In the children with chronic airways diseases there was only a slight increase of SIgA during the first 4 years (mean = 78.0-113.5 mg/l) and an abrupt (statistically significant) rise in the fifth year. The median value of SIgA was 216 mg/l in the children aged 5-13 years. Serum IgA along with salivary IgA were measured in 128 children (r = 0.40, p less than 0.001). 6 children had a complete IgA deficiency and 4 children an incomplete IgA deficiency, i.e. low secretory IgA levels in saliva (36.8-50.0 mg/l) and lacking IgA in serum (less than 14 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1857049 TI - [Sonographic and Doppler color sonographic findings in osteosarcoma]. AB - Till now bone tumors are diagnosed radiologically. In this paper we describe the characteristic sonographic and colour Doppler sonographic features in 5 patients with histologically confirmed osteosarcoma. A large soft tissue tumor with echogenic osteosclerotic areas and echo-free caverns could be shown in all patients. Characteristic signs were destructions of the cortical layer and reactions of the periosteum. Compared to normal tissue an increased number of blood vessels with increased blood flow were visible by colour coded Doppler sonography in the region of the tumor. Sonography and colour coded Doppler sonography are important additions of conventional radiology to describe the structure, extension and blood supply of an osteosarcoma. PMID- 1857047 TI - [Central venous placement of silastic catheters by recording of an intravascular ECG--a prospective study in 50 premature infants weighing less than 1000 g]. AB - In a prospective study 50 central venous silastic catheters were inserted in premature infants weighing less than 1000 g. The position of the catheter tip was checked by recording the intravascular ECG via catheter. All infants were successfully catheterized. The ECG-method proved to be very reliable. Corresponding radiological or ultra-sonographic investigation demonstrated a satisfactory position of the catheter tip in 45 of the infants. The remaining five catheters went into an ideal position close to the superior vena cava-right atrium junction by withdrawing 1-2.5 cm. There were no side effects specific to the ECG-method. The additional use of a diagram concerning the length of introduction given in the text at hand should make X-ray-control unnecessary. We conclude that the ECG-method can be used safely and is of advantage in extremely low birthweight infants. PMID- 1857050 TI - [Tumor necrosis factor in the serum--a useful supplemental parameter in the diagnosis of infection in cystic fibrosis?]. AB - In 15 patients with cystic fibrosis 18 blood samples were investigated for signs of infection including full white blood count, c-reactive protein (CRP) and tumour-necrosis-factor alpha (TNF). Ten patients were hospitalized for pulmonary exacerbation, one for orthostatic collapse and one for equivalent of meconium ileus. The latter two as well as three out-patients with cystic fibrosis on routine-visits served as controls. Blood was taken on admission and at the time of the visit in our out-patient department, respectively. In three cases, blood was taken repeatedly during their stays in hospital. While leucocytosis (17.700 +/- 3.500) and elevated CRP-levels (6.4 +/- 7.3 mg/dl) pointed to an infectious cause of deterioration in the exacerbation-group, TNF-levels without exception were undetectable (less than 15 pg/ml). In the control group, leucocyte counts (10.700 +/- 3.600) and CRP-levels (1.2 +/- 1.1 mg/dl) showed minor pathologic results. TNF-levels were undetectable, too. While elevated TNF-levels measured quantitatively in patients with invasive bacterial infections, e.g. septicaemia due to Neisseria meningitidis, correlate well with prognosis of disease, in patients with cystic fibrosis such a relationship can't be found. PMID- 1857051 TI - [Comparative immunological studies of SID-victims and hospital-treated infants of the same age]. AB - A group of 103 SID victims was compared with a group of 87 clinically treated infants at the same age with respiratory and enteral infections. It was stated that immunological parameters were in agreement in both groups. These findings show that SID victims are ill before sudden death. PMID- 1857052 TI - [Microalbuminuria in children and adolescents with and without Type-I diabetes mellitus (IDDM)]. AB - In 73 healthy (group I) and 32 children and juveniles with insulin dependent diabetes mellitus (IDDM, group II) urinary albumin excretion is determined by radioimmunoassay (RIA). In both groups albumin excretion is observed in every urine sample when measured by RIA (mean +/- SD: group I: 7-19 h: 5.17 +/- 5.28 mg, 19-7 h: 3.86 +/- 4.00 mg, 24 h: 9.03 +/- 8.60 mg; group II: 7-19 h: 6.68 +/- 6.86 mg, 19-7 h: 3.46 +/- 2.82 mg, 24 h: 10.13 +/- 9.25 mg). No significant difference is detected between the values of the two groups. However in diabetic patients a significant difference is observed between diurnal and nocturnal urinary albumin excretion. Microalbuminuria is defined as an albumin excretion above 30 mg/d and is present in 6.9% of the values in group I and in 3.1% in group II. The physiological limits of microalbuminuria in children and juveniles compared to adults and several methods of urine sampling are discussed. PMID- 1857053 TI - [Serum fructosamine in healthy and diabetic children and adolescents]. AB - The determination of fructosamine in serum of healthy newborns, children and adolescents by a new colorimetric method leads to an age-dependent reference range. Correction of the values for total protein yields a median of the results, which is not dependent on age and the upper limit of the reference range is not significantly different from that of healthy adults; this does not hold true for referral to albumin. As the half-life time of glycated serum proteins is shorter (mean 20 days) than that of hemoglobin A1c, fructosamine can provide useful additional informations about the diabetic control of children and adolescents (medium-term record of blood glucose). PMID- 1857055 TI - [Richards-Rundle syndrome]. AB - Among 43 female patients aged 17-46 years with almost severe oligophrenia there were four with primary hypogonadism, one of them a case of Richards Rundle syndrome, now aged 20 years with absence of secondary sex characters, hypoplastic genitals, deafness, ataxia, wasting of muscles and reduced jerks. In cases of hypogonadism and hypogenitalism should be searched for mental and neurologic disorders, also for genetic counseling of the siblings. PMID- 1857056 TI - [100 years of Pfeiffer's glandular fever]. AB - Glandular fever was described by Emil Pfeiffer in 1889. He characterized the disease as an infectious process with fever, a swelling of the lymph nodes including an enlargement of the liver and the spleen and with a pharyngitis. It was the beginning of a very interesting chapter of medical investigations during the next 100 years. The reports of leucocytosis in reaction to this acute infection were the next important step. Sprunt and Evans recommended therefore the term "infectious mononucleosis" in 1920. Further Paul and Bunnell (1932) found the presence of heterophil antibodies in glandular fever. In 1968 Henle and Henle discovered the relations of Epstein-Barr-Virus (EBV) to infectious mononucleosis. In this connection the pathogenesis of glandular fever was investigated. Also the diagnosis of the disease found a certain base by the EBV antibodies and it was possible to give a reliable interpretation of the clinical course, the symptoms and the complications of infectious mononucleosis. Furthermore the atypical manifestation of glandular fever could be identified. In recent years the problems of persistent and chronic infections were discussed. At last the antiviral chemotherapy was tested. PMID- 1857054 TI - [Toxic shock syndrome due to osteomyelitis]. AB - An 11 3/4 year old girl contracted Toxic-Shock-Syndrome following osteomyelitis. The symptoms comprised a severe fall in blood-pressure with centralisation, petechiae and haematoma particularly in the lower extremities, hyperaemia of the oral mucosa and of the throat with profuse and unstaunchable bleeding in this area within in a short period of time. In order to stabilise the blood-pressure the patient had be given approx. 15 l colloidal solution (350 ml/kg) intravenously, mainly frozen-plasma. The risk of aggravation of a pulmonary failure along the lines of ARDS particularly due to the backward flow of the interstitial deposited fluid was avoided by the use of continuous veno-venous haemofiltration (CVVH). PMID- 1857057 TI - [Organization of specialized treatment behind the front line of wounded and sick soldiers in the period of Great Patriotic War (46th anniversary of the victory)]. PMID- 1857058 TI - [Outbreak of clonorchiasis]. PMID- 1857059 TI - [Necessity of amputation of both legs in a patient with myocardial infarction]. PMID- 1857060 TI - [Traumatic defect of interventricular septum]. PMID- 1857061 TI - [Gout yesterday and today]. PMID- 1857062 TI - [Clinical characteristics, diagnosis and therapy of chronic esophagitis]. PMID- 1857063 TI - [Facial pains, diagnosis and therapy]. AB - It is a review of facial pains applied to everyday clinical practice in etiological, pathogenetic, diagnostic and therapeutic aspects. The pains are divided into somatogenic (myogenic and arthrogenic) and neurogenic. Myogenic pain appears in muscular-facial dysfunction while arthrogenic is due to dysfunction of the mandibular joint, craniomandibulohyoid syndrome. Neurogenic pains emerge in trifacial neuralgia, psychalgia, vegetovascular disorders. PMID- 1857064 TI - [Gaps and problems in the moral-psychological education of medical students]. PMID- 1857065 TI - [Rheumatism--current state of the problem]. PMID- 1857066 TI - [History of disease of M.I. Kutuzov]. PMID- 1857067 TI - [The 150th anniversary of establishment of hospital therapy department in the medical-Military Academy]. PMID- 1857068 TI - [Professor P.N. Nikolaev: scientific and medical activity in the years of Great Patriotic war]. PMID- 1857069 TI - [Improvement in the treatment of gunshot wounds of the stomach]. PMID- 1857070 TI - [Prospects of bioregulating therapy]. PMID- 1857071 TI - [Brain neuropeptides and age-related pathology]. PMID- 1857072 TI - [Main principles of chronotherapy]. PMID- 1857073 TI - [Diagnosis and combined treatment of duodeno-hormonal deficiency]. PMID- 1857074 TI - [Soviet neuropathology in the Great Patriotic War 1941-1945]. PMID- 1857075 TI - [Burns as an internal disease]. PMID- 1857076 TI - [The state of bronchial ciliated epithelium and mucociliary transport during chronic bronchitis in long-term smokers]. AB - Endoscopic examination of the bronchial tree and investigation of pulmonary mucociliary transport by aerosol scintigraphy of the lungs were carried out in 40 patients and 10 controls. All the patients had exacerbation of chronic obstructive bronchitis. 20 of these were smokers and 20 nonsmokers. Healthy controls without lung pathology have never smoked. The findings indicate that in chronic sufferers with bronchitis and long history of smoking the rate of mucociliary clearance is reduced to 44% of the normal value and to 65% of the value for nonsmoking patients. This evidence is confirmed by the data obtained on the involvement of bronchial mucosa epithelium and at histologic examination of biopsy specimens. PMID- 1857077 TI - [Differential diagnosis of infiltrative tuberculosis and pneumonia located in the the lower lobe]. AB - Differential diagnosis was made in 2 groups of 85 patients with infiltrative tuberculosis and pneumonia. Clinical, laboratory and x-ray findings confirmed the value of standard examinations (anamnesis, complaints, physical and laboratory methods). Tuberculin diagnosis confirms the primary diagnosis only in case of hyperergic response to the Mantoux test with tuberculin PPD 2 TU. Tracheobronchoscopic detection of nonspecific endobronchitis is not a reliable enough diagnostic criterion to differentiate between tuberculosis and pneumonia. Roentgenologically, tuberculosis is characterized by more frequent polysegmentary lesions and involvement of the VI segment, pneumonia by involvement of the middle lobe, segments VIII and X. PMID- 1857078 TI - [Clinical manifestations and diagnosis of simple lung hypoplasia]. PMID- 1857079 TI - [Immunologic disorders in the pathogenesis of acute lung abscesses]. AB - Immune response was investigated in patients with acute pulmonary abscesses (APA) treated according to the discrete-dynamic scheme. The study of pathogenetic significance of immune response and chronic alcohol intoxication in APA demonstrated that failure of antiinfectious resistance of the body is one of the factors responsible for the onset, course and outcome of APA. This failure is characterized by unbalance of immune parameters, strain of immune system which is more pronounced in the presence of chronic alcoholic intoxication. It is evident that suppression of immune system shown in APA patients is an underlying cause of immunity deficiency in them. PMID- 1857080 TI - [Military medicine during the Great Patriotic War (46th anniversary of the victory over fascist Germany]. PMID- 1857081 TI - [The level of biogenic amines in bronchi of patients with chronic obstructive bronchitis]. AB - Histamine and serotonin levels were measured in expired air humidity condensate (EAHC), bronchoalveolar lavage fluid and sputum of 9 patients with chronic nonobstructive bronchitis and 25 healthy controls. It was found that concentration of biogenic amines depended on the form of chronic bronchitis, activity of bronchial inflammation, characteristics of bronchial obstruction, degree of respiratory insufficiency. EAHC furnished most complete information. PMID- 1857082 TI - [Effect of antibacterial therapy on absorption of food in chronic bronchitis]. AB - An absorptive function of the small intestine was examined in 79 chronic bronchitis patients on antibacterial therapy which is believed to induce dysbacteriosis. These factors seem essential in development of malabsorption syndrome observed in relevant patients. PMID- 1857083 TI - [Effect of laser acupuncture on the pulmonary vascular resistance in patients with obstructive chronic lung diseases]. AB - Clinical pattern of the disease, systolic pressure in the pulmonary artery, external respiration, central hemodynamics were assessed in 111 patients (50 with chronic obstructive bronchitis and 61 with bronchial asthma) to study the effect of laser puncture. The treatment course consisted of 10 sessions performed with application of Uzor apparatus in pulse regimen with 890 nm wave length, 1500 Hz frequency and 2 mW mean radiation rate. The results indicate a positive response to infra-red laser acupuncture evident from improved bronchial patency, enhanced bronchial sensitivity to sympathomimetics, reduced systolic pressure in the pulmonary artery. The promise of the laser puncture is attributed to its separate broncholytic effect and the ability to lower pulmonary vascular resistance. PMID- 1857084 TI - [Tick-borne encephalitis associated with other infections]. AB - Possibility of mixed infection arising in encounter of agents from different families (virus-virus, virus-bacteria, virus-protozoa) was demonstrated on 103 cases of chronic tick-borne encephalitis (TBE) association with other acute and chronic infection. The addition of influenza, tuberculosis, pyogenic infection in most cases entails a relapse of TBE or promotes a primary-progressive course of the disease. TBE association with rheumatic fever relieves pain symptoms. It is emphasized that mixed infections used to bring suppression of immune reactivity thus necessitating serological and virological monitoring of the disease run. PMID- 1857085 TI - [Clinico-morphological characteristics of disseminated intravascular coagulation in bacterial meningoencephalitis]. AB - Clinical, laboratory and morphological manifestations of impaired hemostasis due to CNS bacterial infections varying in etiology were studied in 144 patients and 32 cadavers. Etiologic and age-specific features of hemocoagulatory homeostatic disorders displayed multidirectional procoagulatory, coagulatory and fibrinolytic components. Correlation of morphological evidence for the brain and viscera with clinical-laboratory findings showed that in 69% of the patients who had died of bacterial meningoencephalitis (a generalized form) there were signs of DIC syndrome. These did not always agree clinically with the picture of hemocoagulatory disturbances creating difficulties for its diagnosis. As a result, an intravital diagnosis of DIC syndrome was made in 9% of the patients only. PMID- 1857086 TI - [Surgical treatment of radiation injuries of the hand]. AB - An analysis is given to pilot experience with up-dated plastic surgery techniques in management of hand radiation injuries. Seven patients underwent surgery involving cross-over skin, scapular, radial and inguinal grafts, sliding Littler island graft. The results (both short- and lond-term) turned promising. PMID- 1857087 TI - [Intensive therapy of DIC-syndrome in patients with acute renal insufficiency caused by long-term crush syndrome]. AB - Impairment of parenchymatous organs, primarily kidneys, responsible for their dysfunction in crush syndrome results in many respects from disseminated intravascular coagulation (DIC). It is also associated with hemorrhagic complications. It is demonstrated that treatment modalities aimed at arrest of DIC syndrome (plasmapheresis, heparin, dysaggregation drugs, transfusions of large amounts of fresh frozen plasma) stopped bleeding and septic shock in 12 patients with crush syndrome following the earthquake in Armenia (1988). PMID- 1857088 TI - [Noninvasive diagnosis of pulmonary hypertension in aged and elderly patients with chronic pulmonary heart disease]. AB - Pulmonary hypertension was diagnosed in 97 elderly patients (age 60-79) using electrokymography of the heart and vessels, ECG and rheography of the lungs. All the patients suffered from chronic cor pulmonale (CCP). Electrokymography proved an effective diagnostic tool in detection of pulmonary hypertension in CCP patients, whereas quantitation of the hypertension was successful at electrokymography with application of L. Burstin nomogram and electrocardiography according to S. A. Dushanin. ECG according to R. Bernar et al. appeared poorly sensitive, especially at early CCP stages. A. M. Novikov's rheopulmonography technique can provide only an approximate value of mean pressure in the pulmonary artery of elderly CCP patients. PMID- 1857090 TI - [A case of gasoline pneumonia]. PMID- 1857089 TI - [A case of tactivin side effects in patient with eczema]. PMID- 1857091 TI - Regression of diet-induced atherosclerosis in Gottingen miniature swine. AB - The regression of diet-induced atherosclerosis in Gottingen Miniature Swine was investigated after a 6-month induction period. At 1 month after feeding a high cholesterol and high-fat diet, levels of beta-lipoprotein, total cholesterol, free fatty acids and phospholipid had increased rapidly and the high levels were maintained throughout the 6 month induction period. Morphological features at 6 months showed fatty streaks in the thoracic aorta and fibrous plaques in the abdominal aorta. After return to the conventional diet at 6 months, serum lipids decreased rapidly and maintained the baseline level throughout the 9 month regression period. Histopathological findings showed the regression of fatty streaks but the fibrous plaques did not regress. The present study therefore confirms the regression of fatty streaks in the aorta of Gottingen Miniature Swine by the administration of a cholesterol lowering diet. PMID- 1857093 TI - Pregnancy-associated murine protein-1 plasma levels during oestrus cycle, pseudopregnancy and pregnancy in the mouse. AB - A cyclic variation in plasma levels of pregnancy-associated murine protein-1 (PAMP-1) during the oestrus cycle in outbred Pan: Thei mice was recorded. PAMP-1 plasma levels were significantly elevated in dioestrus as compared with the three other stages of the murine oestrus cycle. Until day 7 of gestation the PAMP-1 plasma levels remained low, and no significant differences could be observed between pregnant and pseudopregnant female mice. The PAMP-1 levels increased markedly in the circulation on day 8 of pregnancy, and continued to increase until peak values were reached at day 11 of pregnancy. In the latter half of pregnancy the PAMP-1 levels declined until day 17 of pregnancy, at which stage the normal non-pregnant values were recorded. PMID- 1857092 TI - The action of trenbolone acetate, a synthetic anabolic steroid, on ovarian function in the guinea pig. AB - The action of trenbolone acetate, a synthetic anabolic steroid, on ovarian function was investigated in the guinea pig. Certain comparisons were made with testosterone, the naturally occurring androgen, administered as the phenylpropionate ester. Two milligrams trenbolone acetate per kg given subcutaneously on alternate days for 20 days blocked oestrous cyclicity and ovulation in 9 of 10 animals. A similar effect was shown by 2.2 mg of testosterone phenylpropionate. Treatment of trenbolone acetate-treated animals with exogenous gonadotrophins suggested that the production of follicle stimulating hormone had been suppressed. Signs of abnormality were seen in the livers of animals receiving 2 mg trenbolone acetate and 2.2 mg testosterone phenylpropionate. PMID- 1857094 TI - Commercial rodent diets and nephrocalcinosis in weanling female rats. AB - This study addresses the questions to what extent commercial rodent diets would induce nephrocalcinosis, and which dietary components would be responsible for inducing this condition. For this purpose, 10 commercial diets were analysed for selected components and fed to weanling female rats. On the basis of histological inspection of kidney sections, two diets were found to produce significant nephrocalcinosis. The condition could be considered relatively mild because concentrations of Ca in kidney tissue were not increased. There was considerable variation between the commercial diets in the (analysed) concentrations of Ca, P, Mg and protein as well as in the diet-induced urinary pH, urinary volume and caecal weight. Of these parameters, only the dietary Ca:P ratio and group mean urinary pH correlated significantly with the observed variation in group mean calcification scores, the relationships being negative. It is suggested that the Ca:P ratio of commercial rodent diets is an important determinant of nephrocalcinosis. PMID- 1857095 TI - Detection of Klebsiella pneumoniae antibodies in Aotus l. lemurinus (Panamanian owl monkey) using an enzyme linked immunosorbent assay (ELISA) test. AB - An enzyme linked immunosorbent assay (ELISA), was adapted to detect antibodies against Klebsiella pneumoniae in Aotus l. lemurinus monkeys. It was used to define the prevalence of infection and the immunogenicity of an Al(OH)3 bacterin in a population of laboratory born A. l. lemurinus monkeys. This represents a preliminary step to reduce K. pneumoniae produced mortality. A striking finding during a cross-sectional prevalence study was that none of the babies of less than 2 months old had detectable levels of antibody. The antibody prevalence gradually increased in all other age groups reaching 87.5% in the 8-10-month-old group. These results indicate that infection with K. pneumoniae occurred sometime between 2 and 6 months of age, probably as a result of oral-faecal contamination and a change in the feeding and grooming behaviour. To determine whether infants had maternal antibodies or if they were asymptomatic carriers of the bacterium, a cross-sectional study was done in 15 infants less than 4 months old and their mothers. K. pneumoniae antibodies were detected in 11/15 mothers with serum titers ranging from 1:4 to greater than 1:256 and the bacterium was isolated from 3 babies and one mother and her baby. Results showed that no maternal antibodies remained in babies older than 3 weeks old. A prospective study indicated a reduction in mortality from 20% for the previous 3 years to 3.7% (3/79) in AL(OH)3 K. pneumoniae bacterin vaccinated infants born during 1988-89. PMID- 1857096 TI - Prevention of catheter-related infections by a new, catheter-restricted antibiotic filling technique. AB - Catheter-related infections pose a hazard to both humans and laboratory animals. The aim of this study was to develop a technique preventing bacterial colonization of intravascular catheters. In 27 dogs a total of 70 catheters were implanted. On an average catheters were used for 207 days. Three protocols were compared: (1) flushing the catheters with a heparinized solution; (2) filling only the catheter lumen with alpha-chymotrypsin solution (225 units/ml); (3) filling only the catheter lumen with a solution containing a mixture of the aminoglycoside antibiotic gentamicin (20 mg/ml) and chymotrypsin (225 units/ml). Catheter fillings were always withdrawn before catheter use. Catheter exit sites were all treated with povidone iodine ointment once a day. Body temperatures and weights were recorded, bacteriological and electron microscopical examinations of catheters performed. Without gentamicin filling all catheters were colonized after a few weeks. The dogs showed clinical signs of chronic bacteraemia. Gentamicin filling eradicated colonization. No further bacteraemia was observed. We conclude that filling only the catheter lumen with a concentrated solution of chymotrypsin and gentamicin, combined with measures to prevent infections via the subcutaneous catheter tunnel, is an effective and safe technique to prevent catheter-related infections. PMID- 1857097 TI - A condition resembling pagetoid reticulosis in a laboratory mouse. AB - A raised, hairless cutaneous nodule was found incidentally at necropsy of a 24 month-old CD1 mouse. Histologically there was infiltration of the epidermis by a monomorphic population of moderate to large lymphocytoid cells. Many large cells had bizarre convolutions of the nuclear membrane and resembled the so-called Sezary or mycosis cells seen in epidermotropic T-cell proliferative disorders. The pattern of cutaneous involvement and the presence of the large cells with convoluted nuclei is characteristic of pagetoid reticulosis. No previous reports of such cutaneous lymphoid neoplasms in mice were found in an extensive literature search. PMID- 1857098 TI - Incomplete protection mechanism against vesico-ureteral reflux and hydronephrosis in the inbred mouse strain DDD. AB - We have previously reported the occurrence and inheritance mode of hydronephrosis in the inbred mouse strain DDD. The present investigation examined the possibility that hydronephrosis may be caused by a vesico-ureteral reflux (VUR). Bladder pressure was measured under anaesthesia in 3 strains of mice (DDD, ddY and C57BL/6). VUR was demonstrated by lower bladder pressure only in the DDD strain. Loading pressure into the renal pelvis (LPP) was significantly higher in DDD than in C57BL/6 (P less than 0.001). Correlations between LPP and severity of hydronephrosis were significantly positive in DDD and ddY, indicating that mice showing higher LPPs had the severest disease. Scanning electron micrography revealed that the ureteral orifice of DDD (100-300 microns) was much larger than in C57BL/6 (30 microns), and thus offered scant protection against VUR in DDD. These results suggest that DDD hydronephrosis caused by VUR is related primarily to the absence of an adequate protection mechanism in the ureteral orifice. PMID- 1857099 TI - Source of information in heart research 1978 and 1988. AB - Several regulatory provisions have been introduced during the last decade that might interfere with the conduct of experimental medical science. In order to study their impact on the source of information within one major field, heart research, a total of 3579 abstracts from the 1978 and 1988 Scientific Sessions of the American Heart Association were analysed with respect to their source of information. There was no change in overall fractions of classical patient studies (45%) or experimental animal studies (30%) for the 2 years although regulations have been introduced in both areas. There was no evidence that the volume of circulatory physiology, a subset that extensively utilizes animal experimentation, declined relative to other subsets of the composite information base. The fraction of cell culture studies clearly rose over the period at the expense of in vitro laboratory studies but not as replacement for animal experimentation. Particularly tight regulations on experiments with selected species apparently explains why dogs and cats are less frequently used relative to rats, rabbits, ferrets and pigs which represent the alternatives. Nevertheless, the absolute number of dog studies doubled over the 10-year period and this species still remains the most widely used experimental model in heart research. The study does not reveal directly what is actually performed within the research community but rather identifies the source of information for those studies that are considered to bring about pertinent new information in modern heart research. PMID- 1857100 TI - The vascularly and luminally perfused small intestine in vitro: dissection technique and model system. AB - The quantitative study in vitro of a wide range of intestinal functions is best achieved by perfusing the intestine simultaneously by the luminal and vascular routes. A comprehensive description is given of the dissections involved in preparing a selected segment of jejunum for such simultaneous perfusions. Attention is drawn to a number of occasional aberrant vascular structures which require special attention if successful perfusions are to be established. It is essential to restore the ATP and diphosphoglycerate concentrations of erythrocytes, and to assess their deformability, before incorporating them in the vascular perfusion medium. The perfusion equipment, the perfusion media and the general conduct of a perfusion experiment, are described. PMID- 1857101 TI - An outbreak of Streptococcus pyogenes infection associated with calcium oxalate urolithiasis in guinea pigs (Cavia porcellus). AB - An outbreak of Streptococcus pyogenes infection occurred in a colony of 800 Dunkin-Hartley guinea pigs resulting in 364 (46%) deaths involving breeders, sucklings, weaners, but mainly adults used as a source of blood meals for haematophagus flies (Glossina palpalis). Clinical signs included bleeding from the nose, mouth and vagina before death. Necropsy revealed pneumonia with consolidation of one or both lungs, haemopericardium and haemothorax. There were yellowish-grey deposits in the urinary bladder of more than 50% of both affected breeders and adults used for feeding haematophagus flies. Beta-haemolytic Streptococcus pyogenes was isolated in pure culture from many tissues including the urinary bladder. The survivors were treated with oxytetracycline (Terramycin LA; Pfizer) using the intra-muscular route and the response was good. PMID- 1857102 TI - Nasal endoscopy: an advancement in diagnosis and treatment of sinusitis. PMID- 1857103 TI - Clinical manifestations of perinatal sexually transmitted diseases. PMID- 1857104 TI - Dr. Chisolm's inhaler: a rare Confederate medical invention. PMID- 1857105 TI - Resurgence of a new "clean living" movement in the United States. AB - During the late 19th century, a "clean living" movement emerged in the U.S. dominated by efforts to control alcohol consumption, tobacco use, and females' reproductive health. The movement also advocated proper diet, exercise and physical fitness, pure water, and moderation in caffeine and red meat consumption. Remarkably similar concerns have emerged again in contemporary American society. The current "movement" lacks central organization. Rather, it reflects a loosely related coalition of single-issue advocacy groups. Yet, the focus seems remarkably similar to the 19th century movement--legislative limitation of individual choice regarding personal health behavior, particularly with substance use and females' reproductive health. This article reviews the 19th century movement, describes aspects of the contemporary movement, and offers implications and recommendations for school health professionals. PMID- 1857107 TI - Utility of the PRECEDE model in differentiating users and nonusers of smokeless tobacco. AB - The utility of the PRECEDE model in identifying factors associated with smokeless tobacco use among male adolescents was investigated. Users and triers were more likely than nonusers to be white, older than average age for their grade, receive below average grades in school, and have had no classroom instruction on adverse effects of smokeless tobacco use. The standard score means of users, triers, and nonusers differed significantly on six of seven PRECEDE model components: attitudes, beliefs, values, perceptions, reinforcing factors, and enabling factors. The standard score means of triers and nonusers, only, differed significantly for the knowledge component. A stepwise multiple regression analysis using all seven model components as predictor variables of smokeless tobacco use accounted for 47.9% of explained variance among users, triers, and nonusers. The values component was the most powerful predictor of smokeless tobacco use (35% of the explained variance). Discriminant function analysis demonstrated the seven components of the PRECEDE mode instrument accurately classified 93.1% of users and nonusers. PMID- 1857108 TI - Restructured schools: challenges and opportunities for school health education. PMID- 1857106 TI - AIDS knowledge, attitudes, and behavior among inner city, junior high school students. AB - To gain information about AIDS knowledge, attitudes, and behavior of junior high school students, 1,967 students in three junior high schools in an inner city school district were surveyed. Ages of the participants ranged from 11-16 years, and 48% were male. Ethnically, 33% were Asian, 31% African-American, 24% Latino, and 5% white. African-American students had greater AIDS general knowledge than Asians and similar general knowledge to Latinos and whites. Most students wanted to be taught about AIDS in school. Misconceptions about casual contagion of AIDS were common. Students with these misconceptions were more likely to believe that students with AIDS should not be allowed to attend school. A high proportion of students had engaged in high-risk behavior including sexual intercourse, drinking alcoholic beverages, and using street drugs. More boys than girls reported each of these activities. Of individuals having had sexual intercourse, a positive association was found between the belief that condoms are effective in preventing HIV infection and use of condoms. These findings support the possibility that improving knowledge about HIV transmission would result in more tolerance toward students with HIV infection and would result in less high-risk behavior. PMID- 1857109 TI - Helping prospective school health educators develop political advocacy skills. PMID- 1857110 TI - Using cooperative learning to integrate math concepts into health instruction on sexuality and HIV education. PMID- 1857111 TI - Food for thought: starting a K-3 nutrition education program. PMID- 1857112 TI - Clinicopathologic correlation quiz: floor of mouth swellings. PMID- 1857113 TI - A technique for the replacement of multiple missing anterior teeth in the presence of a mutilated alveolar ridge. AB - The intent of this paper is to demonstrate a clinical technique for the replacement of multiple missing anterior teeth in the presence of a mutilated ridge. It also reviews basic rules governing the replacement of multiple adjacent missing teeth. The two cases presented clearly demonstrate that multiple adjacent missing teeth can be esthetically restored and still preserve that which remains; teeth, periodontium and soft tissues. The long-term success or failure of prosthodontic restorations relies heavily upon careful consideration of esthetic and foundational requirements. A technique has been described which incorporates the benefits of both fixed and removable dentures to restore multiple missing teeth in the presence of a mutilated alveolar ridge. The first patient was treated approximately twenty years ago. The anterior teeth and alveolar ridge were lost due to an automobile accident. The entire labial alveolar ridge was lost to the base of the nasal spine, thereby making a simple six-unit anterior fixed partial denture a complex and difficult problem. The second patient was recently treated. This patient's alveolar ridge and buccal plate were destroyed by a horse's hoof, again making a restoration procedure a difficult one. PMID- 1857114 TI - Comparative study of bone growth by pulsed electromagnetic fields. AB - Pulsed electromagnetic fields have been widely used for treatment of non-united fractures and congenital pseudarthrosis. Several electrical stimulation systems such as air-cored and iron-cored coils and solenoids have been used the world over and claimed to be effective. Electrical parameters such as pulse shape, magnitude and frequency differ widely, and the exact bone-healing mechanism is still not clearly understood. The study attempts to analytically investigate the effectiveness of various parameters and suggests an optimal stimulation waveform. Mathematical analysis of electric fields inside the bone together with Fourier analysis of induced voltage waveforms produced by commonly used electrical stimulation wave-forms has been performed. A hypothesis based on assigning different weightings to different frequencies for osteogenic response has been proposed. Using this hypothesis astonishingly similar effective values of electric fields have been found in different systems. It is shown that effective electric field rather than peak electric field is the main parameter responsible for osteogenesis. The results are in agreement with experimental findings made on human beings by different investigators. PMID- 1857116 TI - New algorithm for the detection of the ECG fiducial point in the averaging technique. AB - The use of the coherent averaging technique applied to the electrocardiographic signal implies the location of a fiducial point as a synchronisation reference. An algorithm easily adaptable to a personal computer, operable in real time, insensitive to mains and to ECG-baseline fluctuations, with a low jitter value and the capacity to trigger any ECG signal wave or complex, has been developed. The algorithm detects those waveforms which, within certain confidence intervals, are morphologically equal to a reference wave. This wave is chosen by the user as the repetitive waveform within which the fiducial point is to be located. A two window template and differential parameters are used. The possibility of building the template permits the user to adapt the algorithm to each patient's ECG. To evaluate its accuracy objectively, a software simulation was built of a generator capable of producing test signals as the sum of the 'useful' signal plus 'noise'. A jitter standard deviation of 1.65 ms was obtained in the worst test (SNR = 10 dB; noiseband = 0-50 Hz), which shows the excellent recognition accuracy of the algorithm. PMID- 1857115 TI - Continuous measurement of renal cortical blood flow and renal arterial blood flow during stimulation of the renal nerve. AB - Stimulation of the renal sympathetic nerve in young pigs with biphasic pulses of current (3 mA, 800 microseconds per phase, 5, 10 and 50 Hz) produced decreases in arterial and cortical blood flow in the kidney, with the greatest decreases occurring at the highest stimulus frequencies. The decrease in cortical flow lagged that in arterial flow by 1.53-1.99 s; the delay increased with decreasing frequency but was unaffected by captopril, an angiotensin-converting enzyme blocking agent. This result was consistent with the hypothesis that stimulation of the sympathetic nerve causes constriction first in the afferent arteriole and then in the efferent arteriole. Systemic arterial pressure increased during stimulation of the nerve; the increase was greater in intact nerves than in nerves that had been crushed proximal to the point of the stimulus, indicating that pigs do have renal afferent nerves. Pressure increased after the stimulus ended, but the increase abated or changed to a decrease after administration of captopril. The changes in flow were unaffected by administration of captopril, but were markedly reduced by the blocking agent labetalol (renal arterial flow, 77 +/- 14 per cent; cortical flow, 70 +/- 12 per cent). Thus, the observed changes in flow resulted from direct stimulation of the sympathetic nerves and not from stimulation of the renin-angiotensin system, which affects the pressure response after the stimulus. PMID- 1857117 TI - Noninvasive detection of ventricular wall motion by electromagnetic coupling. Part 1. Theory: the changes in the reflected impedance of a coil over a semi infinite medium with properties ranging from lossy dielectric to a conductor. AB - Radiofrequency coils are used as sensors in various applications such as nuclear magnetic resonance (NMR) imaging and displacement cardiograms (DCGs). In most cases the impedance and the resonant frequency of the coil are monitored to provide the required information. The paper describes the changes in reflected impedance and in resonant frequency of a coil when it is placed near a medium with properties ranging from a lossy dielectric to a pure conductor. The theory of interaction between the coil and the medium is investigated and a model based on the use of vector potentials is developed. One prediction of the theory is that placing the coil over body equivalent saline (lossy dielectric) at 15 MHz results in an increase in the inductance of the coil and a resultant decrease in resonant frequency. This prediction was supported experimentally. PMID- 1857118 TI - Noninvasive detection of ventricular wall motion by electromagnetic coupling. Part 2: Experimental: cardiokymography. AB - The cardiokymograph or displacement cardiograph (DCG) is a noncontacting device which senses movement of the heart throughout the cardiac cycle by the interaction of a radiofrequency (10-20 MHz) electromagnetic field, generated by a sensing coil, with the thorax. In the paper three different techniques of detecting this movement will be discussed: monitoring the changes in sensing resonant frequency (FM modulation), monitoring the changes in impedance of the coil at resonant frequency (AM modulation) and a new technique which monitors the changes in coil impedance at fixed frequency. The sensitivities of these three techniques will be compared. A simplified theory of the mode of coupling between the coil and the thorax will be studied in terms of a transformer model. Preliminary clinical measurements of anterior left and right ventricular motion will be given. The presence of higher-frequency features related to atrial motion and the opening and closing of the aortic and pulmonary values will also be described. PMID- 1857119 TI - Measurement of left ventricular heat production in man. AB - A system to measure left ventricular heat production phi iv in conscious human subjects is described. Using phi iv and the rate of energy supply to the myocardium, the mechanical efficiency of the left ventricle is calculated. Heat carriage in left ventricular myocardial blood flow phi cs is calculated from coronary sinus flow and the transcoronary temperature difference. Diffusional heat loss phi diff is derived from the ratio of areas under temperature/time curves recorded in the aorta and coronary sinus after a bolus injection of cold saline into the pulmonary artery. The sum of phi cs, phi diff and phi chem (the energy of endothermic reactions with haemoglobin) gives phi iv. The estimated errors in the derived values of heat production and mechanical efficiency are less than 17 per cent. At basal heart rates 17 patients with good left ventricular function had a transcoronary temperature difference of 0.16 +/- 0.03 degrees C (mean +/- standard deviation), left ventricular flow blood of 145.3 +/- 81.5 ml min-1, and phi iv of 3.1 +/- 1.8 W. Left ventricular oxygen extraction was strongly correlated with phi iv (r = 0.925, p less than 0.001). Left ventricular mechanical efficiency was 0.33 +/- 0.11, at basal heart rates, which fell to 0.18 +/- 0.15 (p less than 0.001) on atrial pacing at 100 beats min-1. PMID- 1857120 TI - Recording of physiological signals with domestic videotape storage. AB - A system is presented for the recording of physiological signals on an unmodified domestic videocassette recorder (VCR). A modification in the vertical synchronism pulses permits the recording of continuous analogue signals without significant loss of samples. The system allows up to 16 input channels, with a maximum bandwidth of 20 kHz for one channel (10 kHz for two channels, 5 kHz for four, or 2.5 kHz for eight) and a minimum of 1.25 kHz for 16 channels, 12-bit resolution, a signal-to-noise ratio of nearly 70 dB and an additional channel for the recording of control and alphanumeric information. The resulting system is reliable, inexpensive, compact and of large capacity, allowing up to 8 h of uninterrupted recording. PMID- 1857121 TI - Parametric method for the detection of inter- and intrasweep variability in VEP processing. AB - The paper introduces a Kalman filter procedure for the processing of single-sweep visual evoked potentials (VEPs). The identification of the filter coefficients is based on a model of signal and noise interaction which considers the generating process as the superposition of the true evoked response to an AR process (the background EEG) and a broader spectrum noise. Intersweep variability is thus evident on the filtered response and a functional parameter of the filter (VP(t), namely variability path) is proposed for the automatic determination of the latencies associated with the main peaks of the response. Finally, the time variant algorithm allows the quantification of the intrasweep variability for possible interpretation of the physiological mechanism involved. PMID- 1857122 TI - Smoothed power spectrum estimate applied for analysis of the Doppler signal from blood flow. AB - A simple method for the improvement of the definition of the instantaneous spectrum estimate of Doppler signal is proposed. A short review of the stochastical properties of FFT spectrum estimates is presented. This review allowed us to develop a concept of the 'estimation noise' as an interpretation of the stochastic uncertainty of the estimation. This, in turn, permitted us to propose a method of adaptive filtering of spectral estimation to minimise the effects of the 'estimation noise'. Proposed filtering in the frequency domain corresponds to a procedure known as smoothing of the estimate. Two different smoothing procedures are presented: classical, linear smoothing and nonlinear, homomorphic smoothing. The performances of the smoothed spectrum estimate are theoretically and experimentally studied, showing that their effectiveness depends mostly on the shape of the Doppler spectrum. Although smoothing always reduces the spectral resolution, the important limitation of the variance of estimation can be achieved without meaningful deterioration of the resolution in our application. Thus, the proposed procedures may sensibly improve the accuracy of the relationship between the shape of the spectrum and the flow parameters. As a result, more exact determination of flow characteristics such as stability or maximum velocity, even in cases of low signal-to-noise power ratio, should be possible. PMID- 1857123 TI - SLOPE--a real-time ECG data compressor. AB - An ECG sampled at a rate of 250 samples s-1 or more produces a large amount of redundant data that are difficult to store and transmit. In the paper, a real time ECG data compressor, SLOPE, is presented. SLOPE considers some adjacent samples as a vector, and this vector is extended if the coming sample falls in a fan spanned by this vector and a threshold angle; otherwise, it is delimited as a linear segment. By this means SLOPE repeatedly delimits linear segments of different lengths and different slopes. The Huffman codes for the parameters to describe this linear segment are transmitted for that linear segment. SLOPEa, which is a slightly modified version of SLOPE, is used to compress ambulatory ECG data. All the operations used by SLOPE and SLOPEa are simple integer operations, both SLOPE and SLOPEa being real-time compressors. Experimental results show that an average of 192 bits per channel per second (bpcs) for each ECG signal is obtained by SLOPE and an average of 148 bpcs for each ECG signal is obtained by SLOPEa. PMID- 1857124 TI - Optimal control system for the intra-aortic balloon pump. AB - An optimal control system for the intra-aortic balloon pump (IABP) is presented. Control of the IABP is based on a performance index formulated to reflect a tradeoff between maximising cardiac oxygen supply and minimising cardiac oxygen consumption. In the performance index, mean diastolic pressure (MDP) was used to represent oxygen availability and peak systolic pressure (PSP) was used to represent oxygen consumption. An algorithm, implemented using an 8-bit microcomputer, changes the deflation time of the IABP to maximise this performance index by using an optimisation technique that employs both a search and an approximation. The search produces three equally spaced points which define a region that includes the maximum of the performance index. From these points, the optimum deflation time is estimated by a quadratic approximation. The algorithm has been successfully tested using performance index curves generated by computer simulations. PMID- 1857125 TI - Autonomous telemetric capsule to explore the small bowel. AB - An intestinal telemetric capsule has been developed to study the small bowel in man. It consists of a cylinder (11 mm in diameter and 39 mm in length) containing a location detector, a radiotransmitter, a lithium battery and an interchangeable tip. After having been swallowed by the patient, the capsule passes through the whole gut and is recovered in the stools. During the transit through the small bowel, the information provided by the radiotransmitter allows continuous monitoring of the distance covered from the pylorus, the direction and the velocity of progression. Moreover, according to the type of interchangeable tip, it is possible, by remote control, to sample 0.5 ml of intraluminal fluid for subsequent analysis or to release 1 ml of any liquid substance in a precisely determined place for pharmacological studies. The main originality of the capsule is its ability to transmit its precise location inside the small bowel. PMID- 1857126 TI - Design and evaluation of closed-loop feedback control of minimum temperatures in human intracranial tumours treated with interstitial hyperthermia. AB - The dynamic nature of blood flow during hyperthermia therapy has made the control of minimum tumour temperature a difficult task. The paper presents initial studies of a novel approach to closed-loop control of local minimum tissue temperatures utilising a newly developed estimation algorithm for use with conductive interstitial heating systems. The local minimum tumour temperature is explicitly estimated from the power required to maintain each member of an array of electrically heated catheters at a known temperature, in conjunction with a new bioheat equation-based algorithm to predict the 'droop' or fractional decline in tissue temperature between heated catheters. A closed loop controller utilises the estimated minimum temperature near each catheter as a feedback parameter, which reflects variations in local blood flow. In response the controller alters delivered power to each catheter to compensate for changes in blood flow. The validity and stability of this estimation/control scheme were tested in computer simulations and in closed-loop control of nine patient treatments. The average estimation error from patient data analysis of 21 sites at which temperature was independently measured (three per patient) was 0.0 degree C, with a standard deviation of 0.8 degree C. These results suggest that estimation of local minimum temperature and feedback control of power delivery can be employed effectively during conductive interstitial heat therapy of intracranial tumours in man. PMID- 1857127 TI - Use of electrical impedance for continuous measurement of stroke volume of a skeletal muscle-powered cardiac assist device. AB - This study describes the use of electrical impedance Z to continuously measure the stroke volume SV of a skeletal muscle-powered ventricle (SMV). An SMV was constructed surgically in four anaesthetised dogs. The rectus abdominis (two dogs) or latissimus dorsi (two dogs) muscle was wrapped around a compressible pouch, the ends of which were connected to a saline-filled (0.9 per cent) mock circulation. The motor nerves to the muscle were stimulated to produce tetanic contractions at a rate of 10 min-1. Z was measured between brass sleeve electrodes within the end conduits of the pouch. To derive a simple expression relating pouch volume V to Z, the pouch was represented as two truncated cones with their bases joined. For V ranging from 53 to 103 ml, the relationship between Z and 1/square root of V was nearly linear; i.e. Z = m(1/square root of V) + b. Impedance-derived stroke volume SV (delta Z) was calculated using this linear approximation and the impedance measured just before and after muscle contraction. The stroke volume SV (EM) ejected by the pouch during muscle contraction was measured with an electromagnetic flowmeter. The linear regression coefficients ranged from 0.99 to 2.55; the correlation coefficients ranged from 0.90 to 0.98. In general, SV(delta Z) tracked SV(EM) very well, although SV(delta Z) tended to overestimate SV(EM). PMID- 1857128 TI - Evaluation of the control function of interstitial osmolarity in coronary autoregulation. AB - A control mechanism for the control of coronary blood flow (especially coronary autoregulation), presuming that interstitial osmotic pressure determines vascular resistance, was critically examined. A theoretical model of the control mechanism was made and the most important parameters of this theoretical model were estimated from published data. The parameters are the slope of coronary autoregulation curves, the sensitivity of coronary resistance to plasma oncotic pressure and capillary resistance. It appeared that the gains of this control loop were not large enough to allow for a dominant role of interstitial osmolarity in coronary autoregulation. PMID- 1857130 TI - Online median filter for ultrasound signal processing. PMID- 1857129 TI - Pressure/flow relationships in collapsible tubes; effects of upstream pressure fluctuations. AB - An experimental investigation has been made on the pressure/flow behaviour of a collapsible tube. Of particular interest are the effects of upstream pressure fluctuations on the mean pressure/flow relationships. These mean pressure/flow relationships were found to exhibit features generally similar to the steady-flow situation, including flow limitation where the flow rate becomes independent of the driving pressure during the tube-collapsed phase. However, the tube collapsed under a higher downstream pressure and the maximum flow rate was reduced, when either the frequency or amplitude of the upstream pressure fluctuations was increased. PMID- 1857131 TI - Organizing the Metro Firm System for research. AB - During the mid-1970s, four similar groups of patients and providers were created with the institution of the Firm System at Cleveland Metropolitan General Hospital (Metro). In the early 1980s, ongoing randomization was initiated for patients and physicians, setting the stage for the performance of randomized controlled trials. Techniques such as stratification and blocking are used with randomization to ensure that equivalent numbers and characteristics of patients and physicians are distributed among the firms. Comparability of key patient and physician features across firms has been documented during the baseline periods of several recent firm studies. Dissimilarities among firms can occur secondary to differential drop-out of patients (residue cohort effect), or to administrative decisions that adversely affect the structural or operational integrity of the system. Prestudy evaluations of equivalence and vigilant system maintenance programs are methods to identify and minimize important differences among firms. PMID- 1857132 TI - Inpatient firms in a teaching hospital. The Henry Ford Hospital experience. PMID- 1857133 TI - The contributions of firms. A fresh movement in medicine. PMID- 1857134 TI - The ethics of ongoing randomization trials. Investigation among intimates. AB - Precisely because firm trials employ experimental designs, it is important that attention be paid to the rights and welfare of the human subjects of these evaluations. This report reviews how administrative firm trials, those that do not directly interfere in the practice of medicine, can be ethically conducted. However, because spiraling health costs are increasing pressures on managers to determine which medical practices are the most cost-effective, we also consider how clinical firm trials comparing accepted diagnostic or therapeutic modalities might be performed. Both of these types of trials require that patients agree to join clinical communities whose routine practice has been redefined to include some level of minimal-risk experimentation. Consequently, it may be appropriate for firm systems formally to adopt a new paradigm of investigation among intimates, one that encourages the participation of patients in all aspects of the research endeavor. PMID- 1857136 TI - Parallel providers, ongoing randomization, and continuous improvement. PMID- 1857135 TI - Alcohol counseling in a general medicine clinic. A randomized controlled trial of strategies to improve referral and show rates. AB - We conducted a controlled trial of two interventions to increase the number of patients receiving alcohol counseling in an academic, general medicine clinic. Ongoing randomization yielded similar groups of patients and providers. By applying a two-item alcoholism-screening instrument incorporated into the routine intake process, nursing staff were successful in screening 90.4% of the 1,328 eligible patients seen during a 4-month study period. Of the patients screened, 428 (35.6%) were found to be positive. In those groups where nurses were allowed to refer directly on the basis of a positive screening result, over four times as many patients (10.8% versus. 2.3%) accepted appointments for counseling, as did patients seen by physicians providing standard care. Patients who were briefly introduced to the alcohol counselor at the time referral were no more likely to keep their first, formal appointments than were patients scheduled in the usual manner. Patients who did receive counseling had their diagnoses confirmed by the 25-item Michigan Alcoholism Screening Test. We conclude that the adoption of an alcohol screening program in our clinic increased the number of patients appropriately referred for counseling. PMID- 1857137 TI - Practice randomization and clinical research. The Indiana experience. AB - Thoughtful preparation of a research laboratory is an early step in designing a program for scientific investigation. The Division of General Internal Medicine at Indiana University has maintained a "laboratory" for outpatient clinical investigation for more than 15 years. In this report, we describe the structure and function of the General Medicine Practice in the Regenstrief Health Center on the campus of the Indiana University School of Medicine in Indianapolis. Specifically, we discuss the ongoing random allocation of subjects, the local resources for data management and tracking of patients' use of clinical services, and how combining this information system into a randomized primary care system has fostered successful ventures in clinical investigation. PMID- 1857138 TI - Initiating the firm system at a community teaching hospital. AB - The Medical Center of Central Massachusetts-Memorial, a 350-bed private community teaching hospital, initiated a firm system for multiple reasons: to improve teaching, improve physician nursing relations, improve discharge planning, and to improve quality assurance/utilization review activities. In this system, private physician groups were randomized to four geographic medical wards, each of which had a distinctive subspecialty identity: oncology, cardiology, nephrology, and diabetes. Primary care internists became the Firm Directors, and subspecialists, already identified with those geographic wards, became Associate Firm Directors. The new system has produced several exciting successes; better bedside teaching and a project to shorten the length of stay of common diagnoses are two examples. Problems remain: resident complaints about imbalanced admissions and an increased census are two issues that we must overcome. PMID- 1857139 TI - Randomized, controlled trials using the Metro Firm System. AB - The Firm System at MetroHealth Medical Center was begun almost two decades ago to foster improved continuity of patient care and teaching of medical students and residents in Internal Medicine. For the past 8 years, these parallel teams of providers and patients also have been used to conduct clinical, educational, and health care delivery research. Randomized, controlled trials are made possible by ongoing random assignment of patients and providers to the three teams, or small group practices. Each group practice has equivalent inpatient and outpatient areas supported by nonrotating nursing, paramedical, and clerical staff. The system's current relationships were established after a controlled trial established both decreased costs and increased effectiveness of the "group practice model" as compared to more traditional approaches to patient care by residents in an academic medical center. Other trials, both on the inpatient and outpatient settings, have been used to guide ongoing institutional change. The unique advantages of the randomized controlled trial are high-lighted by contrasting the results of within-group changes during an intervention with results that incorporate control group changes. A variety of methodologic and logistical issues must be addressed when conducting controlled trials that use ongoing randomization within a single institution. These include determination that the groups are equivalent for all important parameters preintervention, choosing an analytic approach that accounts for potential differences among providers and patients, and, in trials designed to affect behavior, assurance that a "steady state" exists prior to initiating another trial designed to affect similar behavior. Consideration also must be given to the possibilities of cross team contamination, the Hawthorne effect, the "dominant attending effect," and ethical issues related to informed consent. Clinical trials in a single institution may be performed for common problems and those with well defined stages of severity. Since the costs of maintaining the ongoing randomization are relatively small, the incremental costs of conducting randomized controlled trials are low by comparison to traditional approaches. The establishment of analogous systems at other institutions will permit multisite trials for less common clinical problems, enhance the generalizability of findings, and permit new types of health services research, including the rigorous evaluation of practice guidelines. PMID- 1857140 TI - [Distribution of serotypes A and B of Candida albicans in 502 strains isolated from pathological specimens]. AB - BACKGROUND: Candida albicans is distributed in at least two serological groups (A and B) depending on its antigenic structure. These characteristics have been used to investigate the epidemiology of candidiasis. No information is available in this country about the distribution of these serotypes in a general population of patients with candidiasis of different localizations. The aim of the present study was to correlate the frequency of C. albicans serotypes with the origin of the clinical samples. METHODS: In 502 strains of C. albicans isolated from pathological products, serotype was evaluated by means of a latex agglutination test with polyclonal monovalent antisera. A statistical analysis was carried out to investigate whether there was any relationship between the serotype frequency and the origin of the strains. RESULTS: The serotype A of C. albicans represented 78% of all isolates. However, there was a significantly higher relative frequency of serotype B in vaginal and oropharyngeal samples. No differences were found in isolates from AIDS patients. CONCLUSIONS: The serotyping method should be considered a contribution, even if limited, to the knowledge of the epidemiology of Candida albicans infections. PMID- 1857141 TI - [Internist's role in cerebral metastases]. PMID- 1857142 TI - [T lymphoid blast crisis of Philadelphia chromosome-positive chronic myeloid leukemia: analysis of 3 cases]. AB - BACKGROUND: To investigate the frequency of the T lymphoid phenotype in the blast crisis of chronic myelocytic leukemia (CML) with positive Philadelphia chromosome (Ph) and to evaluate the major clinical and hematologic features of the patients with this phenotype. METHODS: The presence of the TdT enzyme was assessed and specific monoclonal antibodies to the different hemopoietic lines were used to evaluate blast cells in 38 patients with blast crisis during Ph-positive CML. RESULTS: T lymphoid phenotype was found in three of the 38 patients, corresponding in all cases to immature T cells. In one patient, the blast crisis was the presenting feature of CML and in two the localization of the blast crisis was lymphadenopathic. In the two patients who could be followed up a favorable response to chemotherapy regimens including vincristine and prednisone was observed. CONCLUSIONS: Although uncommon, T lymphoid blast crisis in CML should no longer be considered exceptional. This phenotypic finding suggests that, at least in some cases, CML originates in a pluripotential stem cell common to all hemopoietic cells, including T lymphocytes. PMID- 1857143 TI - [Idiopathic myelofibrosis with cutaneous extramedullary hematopoiesis]. AB - Idiopathic myelofibrosis is a chronic myeloproliferative syndrome characterized by the proliferation of the three hemopoietic series and the marrow connective tissue and the development of extramedullary hemopoiesis in the liver and spleen. Cutaneous extramedullary hemopoiesis is and uncommon finding, and only thirteen cases have been reported up to now. We report the first case in the Spanish literature. The patient was a 78-year-old male in whom skin lesions preceded the diagnosis of myelofibrosis. These lesions, consisting of violet coloured maculae and papulae, contained elements from the three hemopoietic series. Therapy with hydroxyurea was started, but the patient died because of cardiorespiratory complications. PMID- 1857144 TI - [Computer-assisted design and elaboration of slides]. PMID- 1857145 TI - [Fever, polyarthritis, left hemiplegia and loss of consciousness in a 37-year-old man with T-cell lymphoma]. PMID- 1857147 TI - [CA 15.3: Bayes' theorem]. PMID- 1857146 TI - [Publication of clinical trials and methodological accuracy]. PMID- 1857148 TI - [Megalotrichiasis and poliosis caused by cyclosporin A]. PMID- 1857149 TI - [A descriptive study of 105 patients with cerebral metastasis]. AB - BACKGROUND: To investigate the hospital frequency and natural history of patients with cerebral metastases (CM). METHODS: A retrospective study of patients seen because of CM from 1984 to 1989. They were identified from the discharge reports and the cancer registry (CR). Data of interest were taken from the clinical record and the CR. RESULTS: 105 patients were identified. Mean age was 60 years. There were 77 males. In 44 patients cancer past history was present, in 33 lung cancer was simultaneously diagnosed and in 28 there was no past cancer history and the primary neoplasm was not identified. CM were multiple in 49 patients. In 18 patients CM was single, with no extracerebral neoplasia. Craniotomy was carried out in 22 patients and 11 received postoperative radiotherapy. The probability of one-year survival in the operated and nonoperated group was 27% and 1.5%, respectively (27 +/- 20% and 1.5% +/- 1.5%; 95% confidence intervals). CONCLUSIONS: The frequency of the diagnosis of CM is not negligible and its occurrence virtually always represents a fatal prognosis. About one half are caused by a lung cancer that may have clinically presented with CM. Poor general condition, multiple CM or extracerebral neoplastic disease prevent radical therapeutic intervention in nearly 80% of these patients. Survival with palliative therapy is shorter than that with surgical treatment. PMID- 1857151 TI - [Female physicians as an unused resource]. PMID- 1857150 TI - [Epidemiology of tuberculosis in the Gran Canary Island]. AB - BACKGROUND: The aim of the present study was to obtain information about tuberculosis (TB) in our area that might contribute to assess the status in Spain. METHODS: A meticulous case finding was carried out during 1988 in all the hospitals of the Gran Canaria island. RESULTS: 214 cases were found (rate 32.2) and 77% were admitted to hospitals. In 160 (74%) the involvement was pulmonary and in 82 (37%) it was extrapulmonary. Mean age was 34 years (range 1-84) and 62% were younger than 40 years. 69% were males. Complete data were obtained in 183 cases (85%). 56% were smokers, 34% alcoholic abusers, 15% drug abusers (35% parenteral) and 4% homosexuals. 26% had some risk factor for TB; 14 of them had been infected by the HIV (8 had AIDS). In 64% there was a diagnostic delay longer than one month. Out of the 214 cases, the diagnosis was made by direct microscopy and/or culture in 110 (51%), by consistent pathological findings in 41 (19%), with some of these studies but with negative results in 35 (16%) and only with clinical and radiological criteria in 28 (13%). 96 (60%) of the pulmonary cases had cavitation. The most common therapeutic schedule (84%) was the recommended 9 month regimen. In 54% no recommendation for the investigation of contacts was made. CONCLUSIONS: In the authors' area, the prevalence of TB is higher than in developed countries. It is more common in middle aged individuals, many diagnoses are still made without bacteriologic studies and in a high number of cases investigation of contacts is not carried out. PMID- 1857153 TI - [Advice and handy drugs can be sufficient in bee and wasp venom allergy]. PMID- 1857152 TI - [Better health care for lower costs]. PMID- 1857154 TI - [Future archive as a laser floppy disc in the patient's pocket]. PMID- 1857155 TI - [Terminal intensive care--ethical viewpoints]. PMID- 1857156 TI - [Ritual circumcision of boys should not be done in public health services]. PMID- 1857157 TI - [Errors on dental materials]. PMID- 1857158 TI - [AIDS campaigns have not influenced the use of condoms among young people]. PMID- 1857159 TI - [Laryngeal mask--a new method for free airways in anesthesia and emergency care]. PMID- 1857160 TI - [Zoster should be treated with peroral acyclovir]. PMID- 1857161 TI - [Independent channels give the most important information on essential drug news]. PMID- 1857162 TI - [The medical journals are an outstanding resource of knowledge on drug news]. PMID- 1857164 TI - [Heart-lung radiography after myocardial infarction is of insignificant value for the estimation of prognosis]. PMID- 1857163 TI - [High density lipoprotein prevents coronary heart disease]. PMID- 1857165 TI - [Antibiotic prevention in acute Cesarean section reduces the frequency of infectious complications]. PMID- 1857167 TI - [Epidural abscess--a rare but severe complication after epidural anesthesia]. PMID- 1857166 TI - [Fertilization in vitro is becoming cheaper and easier to perform]. PMID- 1857168 TI - [3, 4, or more. An epidemic of multiple pregnancies]. PMID- 1857169 TI - [Show respect for judgement about benzodiazepines]. PMID- 1857170 TI - [Time for intensive care of acute spinal cord injuries?]. PMID- 1857172 TI - [Tasks for primary health care?]. PMID- 1857171 TI - [It is a human being we treat--not only a disease]. PMID- 1857173 TI - [Reintroduce vaccination against whooping cough. Why wait 5 years?]. PMID- 1857174 TI - [Vestibular assistant--a professional identity]. PMID- 1857175 TI - [Methylprednisolone improves prognosis in traumatic spinal cord injuries]. PMID- 1857176 TI - [The number of railway suicides can and should be reduced. The involved drivers receive crisis help]. PMID- 1857177 TI - [Severe shortages in preventive measures. Both the number and the degree of severity of explosive fires are increasing]. PMID- 1857178 TI - [Drug metabolism is dynamic. It is as adaptable as the immune system]. PMID- 1857180 TI - [A tick-picker is an effective weapon against transmission of Borrelia infections]. PMID- 1857181 TI - [Diabetic patients with good knowledge of their disease have better metabolic control]. PMID- 1857179 TI - [Importance to develop diagnostic methods for different types of schizophrenia. Patients with schizophrenia have recovered in connection with intensive psychotherapy]. PMID- 1857182 TI - [A consensus in Europe--general targets and a 5-year program: the Saint Vincent declaration for better diabetic care]. PMID- 1857184 TI - [Keep the line clear between killing and allowing to die!]. PMID- 1857183 TI - [More distinct limits between health care and research are needed to solve the dilemma of the heads of the hospital departments]. PMID- 1857185 TI - Seasonal variations in circulating levels of progesterone and estradiol in unmated adult female woodchucks (Marmota monax) in captivity. AB - The annual profile of serum levels of progesterone (P) and estradiol-17 beta (E2) was characterized in a seasonally breeding rodent, the woodchuck (Marmota monax). Hormonal levels were determined in serum samples taken at weekly or biweekly intervals from unmated female woodchucks maintained all year indoors under controlled conditions of photoperiod and temperature. Annual fluctuations included a rise of E2 levels during late January through February, followed by a modest increase in plasma P concentrations by late March, the latter attaining peak values during April and May. A temporal dissociation of peak values of circulating levels of P and E2 during the annual reproductive cycle was also detected. The timing of changes in serum levels of P and E2 in these captive woodchucks corresponded to reproductive events during the normal breeding season of the woodchuck in the southern part of its range. PMID- 1857186 TI - The reversal of the effects on HMG-CoA reductase activity and microsome lipid composition in chick livers caused by short-period cholesterol feeding. AB - Chicks of different ages were fed on a cholesterol diet for 48 hours and then switched to a standard diet. HMG-CoA reductase activity and microsomal cholesterol levels, altered by the cholesterol diet, returned to control values in younger chicks after 48 hours on the standard diet. This study clearly shows that early age is an important factor to be taken into account when considering the reversibility of cholesterol-induced membrane alterations. PMID- 1857187 TI - Renal mitochondrial glutathione transport. AB - Freshly isolated tightly coupled rabbit renal cortical mitochondria rapidly accumulated glutathione (GSH) against an electrical and concentration gradient, and in the presence and absence of pyruvate/malate, succinate, antimycin A, or FCCP. Mitochondrial GSH uptake was dependent on medium GSH concentration, was not saturable, and reached equilibrium within 1 min of addition. Mitochondrial GSH uptake was partially inhibited by glycine, ophthalmic acid, and serine but not glutamate, cysteine, gamma-glutamyl-glutamate, or proline. These results show that 1) mitochondrial GSH uptake is by both a carrier-mediated process and by diffusion, and 2) the GSH carrier system has structural specificity with the glycine residue being a recognition site. PMID- 1857188 TI - Differential effects of perinatal hypoxia and anoxia on long term seizure susceptibility in the rat. AB - We have previously demonstrated that hypoxia is acutely epileptogenic in the immature rat but not in the adult. The window during which hypoxia induces seizures in the rat ranges from postnatal day (P) 5-17, with the most severe seizures occurring at P10-12. Perinatal hypoxia resulted in significantly more acute seizure activity than perinatal anoxia. The present study evaluates the long term effects of perinatal hypoxia versus anoxia. Animals were exposed to hypoxia (3%O2) or anoxia (0%O2) at P10 and challenged later in adulthood (P55-60) with administration of pentylenetetrazol (PTZ) (45 mg/kg subcutaneously). Compared to normal littermate controls, the animals which had been exposed to perinatal hypoxia had a significantly higher frequency of generalized convulsions (GC) and a significantly shorter latency to the first myoclonic jerk (MJ) after PTZ. In contrast, perinatal anoxia did not alter long term seizure susceptibility. These results are discussed in context of previous studies which have shown variable long term effects using different models of perinatal hypoxia and/or ischemia. PMID- 1857189 TI - Classic articles in medical computing. PMID- 1857191 TI - Searching gene and protein sequence databases. AB - A large-scale effort to map and sequence the human genome is now under way. Crucial to the success of this research is a group of computer programs that analyze and compare data on molecular sequences. This article describes the classic algorithms for similarity searching and sequence alignment. Because good performance of these algorithms is critical to searching very large and growing databases, we analyze the running times of the algorithms and discuss recent improvements in this area. PMID- 1857190 TI - The human genome. PMID- 1857192 TI - Microcomputers and prevention of drug abuse. AB - In recent years, the psychological treatment of drug addiction has been dominated by an emphasis on learning theory and an interest in minimal and self administered treatment. The computer provides the consummate medium for bringing these components together. This paper reports on two computer-assisted learning programs, one for the prevention of relapse in former heroin users and the other for the promotion of controlled drinking in early-stage problem drinkers. The need for this type of technology is supported by mounting evidence that drug and alcohol misusers prefer self-help to psychotherapy and that most addicts who manage to overcome their addiction do so on their own. PMID- 1857193 TI - An essay towards solving a problem in the doctrine of chances. 1763. PMID- 1857195 TI - GUESS, the great universal educational software system. PMID- 1857194 TI - A real-time analysis of a transplantation program with a personal computer. AB - This study concerns the use of commercial software (a spreadsheet combined with database and graphic functions) to analyze data on kidney transplantation. The program consists of a section containing (macro) instructions, a section for entering data, a database, a set of spreadsheets (one for each field) with which the statistical calculations and summary tables are executed, and a set of diagrams for the final visual output. Three kinds of data are made available: descriptive statistics, actuarial survival rates, and risk factor evaluation. The program can analyze the importance of the variables considered and estimate the effect of a therapeutic or diagnostic maneuver. PMID- 1857196 TI - Progress in the pathogenesis of Legionella pneumophila. PMID- 1857197 TI - Characterization of the Helicobacter pylori urease and purification of its subunits. AB - Helicobacter pylori (formerly Campylobacter pylori) is the causative agent of gastritis in man. Helicobacter pylori cells contain a large amount of an extremely active urease (E.C.3.5.1.5). This enzyme is suspected to be a virulence factor since the ammonium ion produced from urea may be responsible for tissue injury and/or survival of H. pylori in the gastric environment. Helicobacter pylori urease, native relative molecular mass approximately 600,000, was purified by agarose gel filtration and ion exchange chromatography. DEAE-purified urease is highly active and has a Km of 0.48 mM for urea. The enzyme has a pI of 5.93 and is active from pH 4.0 to 10.0, with an optimum at pH 8.0. The purified urease contains nickel and is composed of two protein subunits, with relative molecular masses of 66,000 and 31,000. The subunits were separated and purified and the first 30 N-terminal amino acid residues were determined. A remarkably close relationship was found between both H. pylori urease subunits and jack bean (Canavalia ensiformis) urease, the subunit of which is a single 840 amino acid polypeptide. This subunit is also largely identical to the high molecular mass subunits of the ureases of Klebsiella aerogenes and Proteus mirabilis, evidence that these four ureases are derived from a common ancestral protein. PMID- 1857198 TI - Expression cloning of Yersinia enterocolitica O:3 rfb gene cluster in Escherichia coli K12. AB - The genes of Yersinia enterocolitica serotype O:3 (YeO3) that determine the synthesis of the O-side-chain of the lipopolysaccharide, the rfb region, were cloned into plasmid pBR322. The O-side-chain of YeO3 was expressed by the clone both in Escherichia coli and Salmonella typhimurium indicating that the entire rfb region was included in the clone. It was shown by restriction mapping, deletion analysis and transposition mutagenesis that about 10.4 kilobase pairs of DNA was essential for the synthesis and expression of the O-side-chain. The correct assembly of the O-side-chain on the cell surface of the clone was confirmed by immunofluorescence microscopy and slide agglutination. Immunoblotting using monoclonal antibody specific for the O-side-chain of YeO3 revealed that the O-side-chain material synthesized by the clone in E. coli was similar to that of YeO3. The clone did not show the in vitro temperature variation in O-side-chain expression characteristic of YeO3. Instead analogous O side-chain was produced both at 25 degrees C and at 37 degrees C. Using transposon Tn2507, which carries a promotorless chloramphenicol acetyltransferase (CAT) gene, transcriptional fusions with the target DNA were generated. When testing the ability of mutated clones to produce CAT, transcription was shown to occur in a uniform direction throughout the whole rfb region. In colony hybridizations, using the cloned insert as a probe, homologous DNA was detected only in pathogenic Y. enterocolitica serotypes. PMID- 1857199 TI - Similarity of the tdh gene-bearing plasmids of Vibrio cholerae non-O1 and Vibrio parahaemolyticus. AB - The gene encoding a hemolysin similar to the thermostable direct hemolysin (TDH) of Vibrio parahaemolyticus was previously cloned from a plasmid of Vibrio cholerae non-O1. The gene (designated as NAG-tdh) was subcloned and its nucleotide sequence was determined and compared with reported sequences of the four tdh gene copies encoding TDH, of which three were cloned from the chromosome and one was cloned from a plasmid of V. parahaemolyticus. In the coding region, the NAG-tdh gene had 100% homology with the plasmid-borne tdh gene (tdh4) whereas the NAG-tdh gene was 96.7-98.6% homologous to the three chromosomal tdh genes. The sequences of the NAG-tdh and tdh4 genes were nearly identical in the further upstream and downstream regions. The entire plasmids carrying the two tdh genes were found to be highly homologous when compared by restriction endonuclease and Southern blot analyses. The results suggest that the tdh gene has been transferred between V. cholerae non-O1 and V. parahaemolyticus by a plasmid, directly or indirectly, and that the nucleotide sequences of the tdh gene-bearing plasmids have undergone minor base changes in the respective genetic backgrounds. PMID- 1857200 TI - Characterization of classic and atypical serogroup O:11 Aeromonas: evidence that the surface array protein is not directly involved in mouse pathogenicity. AB - A number of different techniques were used to analyse classic and atypical serogroup O:11 Aeromonas isolates. Five of seven atypical O:11, S layer-negative strains lacking a homogeneous LPS side-chain pattern exhibited varying degrees of mouse pathogenecity. One virulent atypical strain (AH-77) synthesized a surface array protein (SAP) but was unable to anchor it to the cell surface in an intact form, presumably due to a defect in its LPS architecture. Proteinase K digestion to remove the SAP, or growth at elevated temperatures (42 degrees C) to reduce the proportion of SAP synthesized from classic O:11 S layer-positive strains, did not alter their LD50 values in outbred mice. In addition, a spontaneous mutant, AS-180-1, that was S layer-negative was as virulent as the parental S layer positive strain in the mouse model. These results suggest neither the SAP nor the characteristic serogroup O:11 homogeneous LPS side-chain pattern are directly involved in mouse pathogenicity. PMID- 1857201 TI - The effect of growth temperature on the biosynthesis of Yersinia enterocolitica O:3 lipopolysaccharide: temperature regulates the transcription of the rfb but not of the rfa region. AB - The rfb region of Yersinia enterocolitica O:3 (YeO3) that determines the synthesis of the O-side chain of the lipopolysaccharide was cloned and expressed in Escherichia coli K12 previously. The clone did not show the in vitro temperature variation in O-side chain expression known for YeO3, instead analogous O-side-chain was produced at 25 degrees C and at 37 degrees C and both were similar to that produced by YeO3 at 25 degrees C. In Northern blot analysis marked reduction in the amount of rfb-specific mRNA was observed from YeO3 grown at 37 degrees C when compared with those grown at 25 degrees C. On the other hand, equal amounts of rfb-specific mRNA were detected in the E. coli clone at both growth temperatures. This indicates that the transcription of YeO3 rfb region is dramatically repressed at 37 degrees C. The repressor gene is located outside the rfb region with no analogous locus in E. coli chromosome. We cloned 18.2 kilobase pairs of YeO3 chromosomal DNA that rendered E. coli K12 reactive with 2B5, a YeO3 core-specific monoclonal antibody, in colony blotting, indirect immunofluorescence and immunoblotting. Hence this clone contains the YeO3 rfa region, encompassing the genes involved in the core oligosaccharide biosynthesis. No apparent difference, in the aforementioned tests, was noticed in the expression of the 2B5 epitope at different growth temperatures either in YeO3 or in E. coli. In Northern blot analysis comparable amounts of rfa-specific mRNA were detected at 25 degrees and 37 degrees C. This argues that in YeO3 the core oligosaccharide biosynthesis is not temperature-regulated. PMID- 1857202 TI - The Escherichia coli cell cycle: one cycle or multiple independent processes that are co-ordinated? AB - In the life cycle of a bacterium there are several key processes: cellular growth, chromosome replication and decatenation, nucleoid partition, septum formation, and cell division. These processes have to be carefully controlled and co-ordinated both with respect to each other and to the growth of the cell, and could be viewed as parts of a single cycle in which each step is dependent upon the previous one. Alternatively, they could be independently controlled and carefully tuned to each other without actually constituting a true cycle. In this review, using Escherichia coli as model system, we discuss these two ways of describing the bacterial life cycle. The evidence supporting independent control of the processes is presented, and some of the key questions in the elucidation of the regulation of the bacterial life cycle are discussed. PMID- 1857203 TI - Calcium in bacteria: a solution to which problem? AB - Calcium and calcium-binding proteins including those resembling calmodulin are implicated in numerous diverse processes in bacteria. These processes include chemotaxis, sporulation, virulence, the transport of sugars and proteins, phosphorylation, heat shock, the initiation of DNA replication, septation, nucleoid structure, nuclease activity and recombination, the stability of the envelope, and phospholipid synthesis and configuration. That such varied processes should have a common factor, calcium, suggests major underlying principles of calcium metabolism which have yet to be discovered. PMID- 1857204 TI - Local DNA topology and gene expression: the case of the leu-500 promoter. AB - Many promoters are sensitive to DNA supercoiling, and it is becoming apparent that this may play an important role in gene regulation. The twin supercoiled domain hypothesis (Liu and Wang, 1987) proposes that transcription can lead to local variation in supercoiling. The mutant leu-500 promoter has presented a long standing problem to the understanding of the control of promoter function by DNA supercoiling. This promoter is activated by mutations in the gene encoding topoisomerase I, but is apparently unaffected by mutations in the genes encoding DNA gyrase. We propose a model to explain the anomalous regulation of this promoter, based on the twin supercoiled-domain model. This allows us to account for the unusual properties of the leu-500 promoter, and confirms the biological importance of the twin supercoiled-domain model. We suggest that such topological coupling between promoters may be general, leading to co-operativity and anti-co operativity between divergent promoter pairs. PMID- 1857205 TI - A suppressor of yeast spp81/ded1 mutations encodes a very similar putative ATP dependent RNA helicase. AB - The spp81/ded1 mutations were isolated as suppressors of a Saccharomyces cerevisiae pre-mRNA splicing mutation, prp8-1. The SPP81/DED1 gene encodes a putative ATP-dependent RNA helicase. While attempting to clone the wild-type SPP81/DED1 gene we isolated plasmids which were able to suppress the cold sensitive growth defect of spp81 mutants. These plasmids encoded a gene (named DBP1) which mapped to chromosome XVI and not to the SPP81/DED1 locus on chromosome XV. The cloned gene suppressed the defect of spp81/ded1 mutants when present on both high and low copy-number plasmids but complemented spp81/ded1 null mutants only when present on high copy-number plasmids. In contrast to the SPP81/DED1 gene the DBP1 gene was not essential for cell viability. The nucleotide sequence of the DBP1 gene revealed that it also encoded a putative ATP dependent RNA helicase which showed considerable similarity at the amino acid level to the SPP81/DED1 protein. PMID- 1857206 TI - Characterization of the RNA polymerases of Crithidia fasciculata. AB - We have characterized the crithidial RNA polymerases (RNAPs). The RNAPs from this organism were resolved by chromatography and could be classified into RNAP I, II and III because of their differential sensitivity to class-specific RNA polymerase inhibitors, such as alpha-amanitin (ama) and tagetitoxin. The three RNAP classes were subsequently characterized in nuclear run-ons using class specific DNA templates and the inhibitory effect of ama on RNA chain elongation. These experiments showed that Crithidia fasciculata contains the normal set of eukaryotic RNAPs. However, RNAP II was found to be relatively resistant to ama, which seems to be a general feature of kinetoplastid parasites. Tagetitoxin, a potent inhibitor of purified crithidial RNAP III, does not inhibit RNAP III in nuclear run-on experiments, suggesting that the inhibitory effect of tagetitoxin depends on the enzyme conformation, i.e. 'naked' enzyme versus that in a transcription complex. Finally, the role of RNAP III in the transcription of the mini-exon genes, which provide the 5' end of each mRNA, is discussed. PMID- 1857207 TI - The IgA-binding beta antigen of the c protein complex of Group B streptococci: sequence determination of its gene and detection of two binding regions. AB - The beta antigen of the lbc protein complex of Group B streptococci is a cell surface receptor which binds the Fc region of human immunoglobulin A (IgA). Determination of the nucleotide sequence of the beta antigen gene shows that it encodes a preprotein having a molecular weight of 130,963 daltons and a polypeptide of 1164 amino acid residues that is typical of other Gram-positive cell-wall proteins. There is a long signal sequence of 37 amino acids at the N terminus. Four of the five C-terminal amino acid residues are basic and are preceded by a hydrophobic stretch that appears to anchor the C-terminus in the cell membrane. To the N-terminal side of this hydrophobic stretch is a putative cell-wall-spanning region containing proline-rich repeated sequences. An unusual feature of these repeated sequences is a three-residue periodicity, whereby every first residue is a proline, the second residue is alternating positively or negatively charged, and the third residue is uncharged. The IgA-binding activity was approximately localized by expressing subfragments of the beta antigen as fusion proteins. Two distinct but adjacent DNA segments specified peptides that bound IgA, which indicates that the IgA-binding activity is located in two distinct regions of the protein. PMID- 1857208 TI - Two distinct steps in pullulanase secretion by Escherichia coli K12. AB - Two distinct steps in the secretion of the extracellular, cell-surface-anchored lipoprotein pullulanase by Escherichia coli were uncoupled by allowing export of the enzyme to the cytoplasmic membrane via the signal peptide/sec-gene-dependent general export pathway, and then inducing the pulC-O operon of genes required for translocation to the cell surface. The secretion intermediate cofractionated mainly with intermediate-density vesicles when cells were gently lysed and the resulting vesicles were separated by isopycnic sucrose density centrifugation. Cytoplasmic forms of pullulanase (which are not exported because they lack a functional signal peptide) are more sensitive to heat inactivation, denaturation by sodium dodecyl sulphate and carboxymethylation than the intermediate and cell surface forms. The latter are distinguished only by the fact that the secretion intermediate is less susceptible to proteinase K and trypsin, and is partially inaccessible to substrate or in an inactive conformation in sphaeroplasts. These and other results indicate that the secretion intermediate can acquire considerable higher-ordered structure, including disulphide bridges, before it is transported to the cell surface; this seems to rule out the possibility that it is threaded through this membrane as a locally unfolded polypeptide. PMID- 1857209 TI - Temperature-regulated expression of invasion genes in Shigella flexneri is controlled through the transcriptional activation of the virB gene on the large plasmid. AB - The invasion phenotype of shigellae is subject to thermoregulation that is known to be expressed through activation of some invasion (inv) genes such as ipaB, ipaC, and ipaD encoded by the large virulence plasmid of Shigella flexneri. The expression of ipa genes is regulated positively by virF through the activation of virB on the plasmid. To identify the mediator for the thermoregulation of the large plasmid, we have studied the effect of temperature on the transcription of virF and virB genes and ipa and the other two inv operons. The results showed that transcription of virB was affected by temperature more strictly than that of virF. Analysis of the mRNA level of virB at different levels of virF transcription indicated that virB transcription depended upon both temperature and virF. On the other hand, transcriptions of ipa and the other two inv operons depended on the activation of virB transcription but not on temperature. By inducing virB transcription from a tac promoter fused with the virB region, invasion ability was restored to a virF-deletion mutant at 30 degrees C as well as at 37 degrees C. By using conditions in which the temperature-dependent expression of the invasion phenotype was circumvented by the induction of virB transcription, intercellular spreading ability in a virF+, virB::Tn5 strain was shown to be expressed even at 30 degrees C. These results suggest that the virB transcription stage is the main target for the thermoregulation. PMID- 1857210 TI - Formation of Rhizobium phaseoli symbiotic plasmids by genetic recombination. AB - We report here the formation of symbiotic plasmids (pSyms), by genetic recombination between rearranged pSyms, which lack symbiotic information, and resistance plasmids carrying parts of different symbiotic plasmids (R's). This recombination was found to occur both between plasmids derived from different Rhizobium phaseoli isolates, and between plasmids derived from strains obtained from the same original isolate. We also present evidence on the formation of a functional symbiotic plasmid by recombination of an R', carrying nif and nod genes from strain CFN42, and an indigenous plasmid present in this strain (pCFN42e), which was thought to be unrelated to its symbiotic plasmid (pCFN42d). These data are discussed with respect to the stability and transfer of Rhizobium symbiotic information. PMID- 1857211 TI - Isolation and properties of the RepA1 protein of the IncFII replicon, RepFIC. AB - The initiator protein RepA1 of the IncFII replicon RepFIC derived from the enterotoxin plasmid EntP307 has been cloned under the control of the lambda PL promoter. This has enabled us to overproduce this protein and study its properties. Here we show that RepA1 is a soluble basic protein with an experimentally determined molecular weight of 40,000. Deletion analysis indicates that the overproduced protein originates from the open reading frame which we previously designated as coding for RepA1. We have also shown that the replication function of the replicon RepFIC depends on the intact RepA1 coding frame. PMID- 1857212 TI - The surface-located YopN protein is involved in calcium signal transduction in Yersinia pseudotuberculosis. AB - The low-calcium response (lcr) is strongly conserved among the pathogenic Yersinia species and is observed when the pathogen is grown at 37 degrees C in Ca(2+)-depleted medium. This response is characterized by a general metabolic downshift and by a specific induction of virulence-plasmid-encoded yop genes. Regulation of yop expression is exerted at transcriptional level by a temperature regulated activator and by Ca(2+)-regulated negative elements. The yopN gene was shown to encode a protein (formerly also designated Yop4b) which is surface located when Yersinia is grown at 37 degrees C. yopN was found to be part of an operon that is induced during the low-calcium response. Insertional inactivation of the yopN gene resulted in derepressed transcription of yop genes. A hybrid plasmid containing the yopN gene under the control of the tac promoter fully restored the wild-type phenotype of the yopN mutant. Thus the surface-located YopN somehow senses the calcium concentration and transmits a signal to shut off yop transcription when the calcium concentration is high. PMID- 1857213 TI - Modular structure of FixJ: homology of the transcriptional activator domain with the -35 binding domain of sigma factors. AB - The FixL/FixJ two-component system is a global regulator of nitrogen-fixation genes in Rhizobium meliloti. The transcriptional activator FixJ contains two modules: its N-terminal module is homologous with other two-component regulators; its C-terminal module shows homology with various transcriptional activators, and with the C-terminal region of sigma factors, which is involved in the discrimination of the -35 region of bacterial promoters. We show that the C terminal module of FixJ contains the entire transcription activation function, and that the N-terminal module regulates this activity negatively. Oligonucleotide-directed mutagenesis of the transcriptional activator module demonstrated the importance of a potential helix-turn-helix structure. PMID- 1857214 TI - Peptide growth factors. PMID- 1857215 TI - Phosphorylation and identification of phosphorylated forms of basic fibroblast growth factor. PMID- 1857216 TI - Derivation of monoclonal antibody to basic fibroblast growth factor and its application. PMID- 1857218 TI - Molecular and biochemical approaches to structure--function analysis of transforming growth factor alpha. PMID- 1857217 TI - Generation of antibodies and assays for transforming growth factor alpha. PMID- 1857219 TI - Assessment of biological activity of synthetic fragments of transforming growth factor alpha. PMID- 1857220 TI - Purification of amphiregulin from serum-free conditioned medium of 12-O tetradecanoylphorbol 13-acetate-treated cell lines. PMID- 1857221 TI - Identification of phosphorylation sites: use of the epidermal growth factor receptor. PMID- 1857222 TI - In vitro transcription of epidermal growth factor receptor gene. PMID- 1857223 TI - Expression and purification of recombinant insulin-like growth factors from Escherichia coli. PMID- 1857224 TI - Generation of antibodies and assays for transforming growth factor beta. PMID- 1857225 TI - Purification of transforming growth factors beta 1 and beta 2 from bovine bone and cell culture assays. PMID- 1857226 TI - Assay of astrocyte differentiation-inducing activity of serum and transforming growth factor beta. PMID- 1857227 TI - Erythroid differentiation bioassays for activin. PMID- 1857228 TI - In vivo assay of neuron-specific effects of nerve growth factor. PMID- 1857229 TI - Bioassay, purification, cloning, and expression of mullerian inhibiting substance. PMID- 1857230 TI - Purification and characterization of recombinant melanoma growth stimulating activity. PMID- 1857231 TI - Purification, cloning, and expression of platelet-derived endothelial cell growth factor. PMID- 1857233 TI - Preparation and bioassay of connective tissue activating peptide III and its isoforms. PMID- 1857232 TI - Purification and cloning of vascular endothelial growth factor secreted by pituitary folliculostellate cells. PMID- 1857234 TI - Purification of growth factors from cartilage. PMID- 1857235 TI - Assay and purification of naturally occurring inhibitor of angiogenesis. PMID- 1857236 TI - Derivation of monoclonal antibody directed against fibroblast growth regulator. PMID- 1857238 TI - Assays for bone resorption and bone formation. PMID- 1857237 TI - Localization of peptide growth factors in the nucleus. PMID- 1857240 TI - Transgenic mouse models for growth factor studies. PMID- 1857239 TI - 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate as noncytotoxic stabilizing agent for growth factors. PMID- 1857241 TI - Biaffinity chromatography of fibroblast growth factors. PMID- 1857242 TI - Cloning, recombinant expression, and characterization of basic fibroblast growth factor. PMID- 1857243 TI - Robust trend analysis in predicting histamine provocation concentration. AB - Trend analysis is used to predict the histamine provocation concentration PC20 during the so-called challenge test, where increasing doses of the bronchoconstricting agent are given to a patient and the spirometric examination is subsequently performed. Classical least-squares analysis of trends as well as least absolute deviations analysis are compared. The results are interesting and promising from a statistical as well as medical point of view. The methods presented can be applied to many practical problems in medicine. PMID- 1857244 TI - Adjusting for recall bias with the proportional hazards model. AB - In studying falling frequency in the elderly, we observed that having subjects keep a diary led to a larger number of falls reported than had been noted in a previous study in the same population. The previous study asked subjects to report any falls in the previous three months. We considered two related explanations for the observation of lower incidence reports with a 3-month recall survey. First, there may have been under-reporting of falls due to recall bias. Second, the less severe falls (which did not result in injuries) may not be reported. We suggest that the proportional hazards model may be used to adjust studies in which recall is used to determine incidence and time to falls. PMID- 1857245 TI - Multivariate procedures to describe clinical staging of melanoma. AB - Analyzing multivariate clinical data to identify subclasses of patients being treated for a specific disease may improve patient management and increase understanding of the behavior of disease under clinical conditions. In some cases, patients have been classified on prognostic characteristics using standard risk assessment procedures (e.g., Cox' regression). This requires long term follow-up, differentiates patients only on attributes relevant to survival, and assumes that patients are sampled from a common population. Other approaches involve the use of clustering algorithms to classify patients into categories based on multiple clinical attributes. We illustrate the use of a multivariate statistical procedure to directly characterize patients on multiple clinical characteristics. The procedure is designed to analyze discrete response data with parameters representing individual differences within groups. Its use is illustrated for patients with Stage I melanoma in determining how age is related to treatment response in different patient groups. PMID- 1857246 TI - Record linkage strategies. Part I: Estimating information and evaluating approaches. AB - Record linkage techniques can help identify the same patient for matching diverse files (hospital discharge abstracts, insurance claims, registries, Vital Statistics data) which contain similar identifiers. Prior knowledge of whether a linkage is feasible is important to prevent wasted effort (additional data collection or data manipulation), which decreases the cost-effectiveness of the linkage. Using examples generated by linking the Manitoba Health Services Commission data with Vital Statistic files, a method of estimating the information in each data set is presented first. Further, the feasibility of several different record linkage strategies is described and tested, given varying amounts of information. At the margin, relatively small amounts of information (having just one more variable to match with) can make a great difference. Probabilistic linkage's great advantage was found in those situations where only a moderate amount of extra information was available. By using the above techniques when working with one or both files in a proposed record linkage project, a much more informed judgement can now be made as to whether a linkage will or will not work. In facilitating record linkage, flexibility of both software and the strategy for matching is very important. PMID- 1857247 TI - Controlled trial on medical birth notification design. AB - In a controlled trial, two different forms were compared with respect to thoroughness of completing medical data on procedures during pregnancy, labor, and in newborns. The contents of 547 forms filled in by hospital personnel were compared to data abstracted from hospital records by trained research assistants. Forms with open-ended questions lacked information on 29% of the most common procedures and forms with a check-box format 9%. The results support the use of the check-box format in routine collection of data on common medical procedures. PMID- 1857248 TI - Global schistosomiasis database: practical considerations in the design of a user friendly database. AB - A computerized database for monitoring global schistosomiasis data is discussed. The potential target users include schistosomiasis program managers, Ministries of Health of endemic countries, consultants, and WHO Regional Offices. The concept behind the design of the database structure, the user interface and the query interface is addressed along with a brief description of the hardware and software used. The database, holding information on 76 schistosomiasis endemic countries around the world, has been tested in the WHO Regional Offices with positive results. PMID- 1857249 TI - Surveillance of occupational risks using job-exposure matrices. AB - This article deals with the problem of surveillance of occupational risks of workers. Computer-assisted elaboration of the job history (JH) for each worker was achieved by means of a job-exposure matrix (JEM) for each company. The final aim of the project is to find correlations between the exposure data of JHs and the health data of corresponding medical records. As a first experiment, some JEMs were computed using rectangular arrays even though it was realized that this simple structure was not really adequate. Later on, the structure of the computerized JEM included the following questions: (1) what types of information are involved; (2) how can the job-exposure correspondence be represented in the computer; (3) what characteristics of a company should be used for the elaboration of a JEM; (4) who is to construct each JEM, and how? This article shows the inadequacy of some occupational names for evoking the appropriate risks, a drawback which can be surmounted if the company organization is included in the JEM. Based on our analysis, several specifications useful for JEM computerization have been suggested. PMID- 1857250 TI - Graphical non-linear representation of multi-dimensional laboratory measurements in their clinical context. AB - A polygon-based graphical representation of laboratory test results using nonlinear scaling is described. It is argued that the nonlinearity of the scale and the use of colors in the representation facilitates interpretation of the test result in its relationship to the standard reference range and critical clinical decision levels. Preliminary results suggest that this representation may be fruitfully used to enhance the efficiency of the information transfer from the clinical chemistry laboratory to clinicians. Other applications, inside as well as outside the medical field, may easily be imagined. PMID- 1857251 TI - Is a picture worth a thousand medical words? A randomized trial of reporting formats for medical research data. AB - Monitoring data that vary over time is an essential component of medical practice. This is doubly true in clinical trials in which the overall safety and efficacy of investigational treatments in populations must be monitored in addition to the status of the individual patients who receive them. We report the results of a randomized trial of four reporting methods for time-dependent information derived from clinical trials; narrative text, table, pie chart and icon. Multivariate analysis of variance with a repeated measures design was used to analyze the efficiency of subjects' (physicians, research nurses and laboratory personnel) assimilation of information. Icons were found to be superior to the other reporting formats tested in both speed (p less than 0.0001) and accuracy (p = 0.02). The differences were most pronounced in subjects' first exposure to the data, suggesting that icons reduce the time needed for training. We conclude that icons are a valuable method for presentation of time-dependent information in medical settings. PMID- 1857252 TI - Use and abuse of computer-stored medical records. PMID- 1857253 TI - Algorithms for Bayesian belief-network precomputation. AB - Bayesian belief networks provide an intuitive and concise means of representing probabilistic relationships among the variables in expert systems. A major drawback to this methodology is its computational complexity. We present an introduction to belief networks, and describe methods for precomputing, or caching, part of a belief network based on metrics of probability and expected utility. These algorithms are examples of a general method for decreasing expected running time for probabilistic inference. We first present the necessary background, and then present algorithms for producing caches based on metrics of expected probability and expected utility. We show how these algorithms can be applied to a moderately complex belief network, and present directions for future research. PMID- 1857254 TI - Problem area formation as an element of computer aided diagnosis: a comparison of two strategies within quick medical reference (QMR). AB - INTERNIST-I's use of "partitioning" to group related diagnoses into problem areas (for competitive consideration and elimination during case analysis) is felt to be the source of many of its strengths as well as some of its weaknesses. QMR, INTERNIST-I's successor program, embodies a homology function which can act as an alternative to the partitioner for problem area formation. This study undertakes a comparison of the problem areas generated by the INTERNIST-I partitioning algorithm, the QMR homology function, and expert clinicians; it finds the correlation to be poor. The authors then discuss another method of problem area formation which might better mimic a human clinician and provide an alternative approach in diagnostic computer-aided decision making. PMID- 1857255 TI - Distribution-free confidence bounds for ROC curves. AB - ROC curves are widely used for the evaluation of diagnostic tests to decide between "healthy" and "diseased" individuals when the measurements are on a continuous scale. These curves are graphical displays of the interdependence between specificity and sensitivity of the test varying with the cut-off point chosen for the decision. Up to now only point estimators derived from the empirical distribution functions are used which may be misleading if they are based on rather small samples. In this paper we propose reasonable confidence bounds for ROC curves and a corresponding point estimator. Our bounds are strongly related to two-sided distribution-free tolerance regions because they are constructed from minimum and maximum coverages which at a given value chi can be guaranteed with a confidence (2 pi*-1). The interpretation of the bounds is that if a cut-off-point is chosen on the basis of the ROC curve then with a nominal confidence of at least (2 pi*-1)2 the real sensitivity and specificity will be within a rectangle. PMID- 1857256 TI - The midwife's contribution to the health of women and children. PMID- 1857257 TI - Safest birth attendants: recent Dutch evidence. AB - Analysis of national perinatal statistics from Holland, 1986, demonstrates that for all births after 32 weeks' gestation mortality is much lower under the non interventionist care of midwives than under the interventionist management of obstetricians at all levels of predicted risk. This finding confirms with great authority the conclusions of all earlier impartial analyses from Britain and other countries which agree in contradicting the claims on which the organisation of maternity services in most developed countries is now based, namely, that childbirth is made so much safer by the application of high technology that only this option should be provided. PMID- 1857258 TI - Postpartum haemorrhage: its contribution to maternal mortality. AB - Postpartum haemorrhage is the major cause of maternal mortality in the developing world. This paper presents the incidences and discusses the causes and strategies for its prevention. The paper is based on one originally given at the ICM/WHO/UNICEF pre-congress workshop in Kobe, Japan, Oct, 1990. PMID- 1857259 TI - Fistulae of obstetric origin. AB - World Health Organization (WHO) estimates that in the developing countries 5 million women each year suffer severe maternal morbidity and high on this list is obstetric fistulae (vesico-vaginal and/or recto-vaginal). This article tries to explain why these fistulae still occur, comments on measures of prevention and how treatment might best be provided for those women who suffer from this terrible affliction. PMID- 1857261 TI - Rooming-in at night in the postpartum ward. AB - Since the early 1970s it has been common practice for 'rooming-in' to take place during the day in Swedish maternity wards. At night newborn babies are usually looked after by nursing staff in special nurseries. One reason for this is to avoid disturbing the mothers' sleep at night. To promote mother-infant adaptation, we undertook a programme intended to encourage night-time rooming-in. Evaluation of the programme was carried out as a quasi-experiment, divided into a pretest period (I), a 6-month implementation period, and a post-test period (II). Breast feeding and maternal sleep were studied during the first 3 postpartum days by means of self-report by 104 mothers in Period I and 111 mothers in Period II. The number of hours that the babies spent in the nursery decreased from Period I to Period II, a difference that was most obvious during the second and third postpartum nights. No difference was found in the number of breast feeds in Periods I and II, except during the third night, when Period II mothers breast fed more often. In spite of increased rooming-in in Period II, these mothers slept the same number of hours and felt equally alert as Period I mothers. PMID- 1857260 TI - Consumer interest in alternatives to physician-centred hospital birth in Ottawa. AB - A survey of 1109 women who delivered in a hospital or at home in a major city in Canada was conducted. The women were asked to respond to questions concerning the type of health professional they would like to provide reproductive care. The choices they were offered were: midwife, obstetrician, general practitioner or nurse, or a combination. Respondents were also asked to identify if they had an interest in an alternative such as a birthing room, birthing centre or home birth, to hospital labour ward care. Almost 60% of women were interested in some form of midwifery care with the major emphasis placed on counselling and support. Of the women who expressed an interest in midwifery services a large number elected for that service to be shared with an obstetrician. Women who were older and had achieved a high level of education were more interested in midwifery services than other women. If given choices of a hospital labour, birthing room, birthing centre or home birth 53% of women would choose to give birth in a hospital labour ward. A major reason for this choice was the accessibility of epidural analgesia. The majority of women who had experienced a home birth would make the same choice again. There was a strong positive association between interest in using midwifery services and interest in a birthing centre and home birth. PMID- 1857262 TI - Marie Goubran. PMID- 1857263 TI - The correlation of biochemical virulence factors and enterotoxin production with LD50 of Salmonella typhimurium in mice. AB - Five strains of Salmonella typhimurium were examined to determine the parameters of virulence. The virulent species significantly resisted the macrophage bactericidal activity (p less than 0.05). The chemiluminescent (CL) response was studied to determine the level of Oxygen-free radicals (OFR) generated and the antioxidant enzymes superoxidase dismutase (SOD), catalase and glutathione peroxidase were assayed to determine the antioxidant mechanism of S. typhimurium to subvert these microbicidal pathways. The levels of the various enzymes were correlated with the virulence (as determined by LD50) and the ability of the microorganisms to induce diarrhoea. Oxygen free radical (OFR) generation elicited by macrophages, in the presence of virulent and avirulent salmonellae was not statistically significant (p greater than 0.05). No correlation was found between the levels of the antioxidant enzymes and the LD50 values. Thus the oxygen dependent pathways do not appear to play a role in the pathogenesis of salmonellosis, and do not specify the virulence of the microorganism. Immunological and biological assays revealed the virulent strain to be more toxigenic than the avirulent strain. Therefore, the basis of differing virulence in S. typhimurium may be the ability to make and release more toxin in vivo. PMID- 1857264 TI - Serum-mediated killing of Salmonella typhimurium and Escherichia coli mutants which share a different content of major proteins. AB - Salmonella typhimurium and Escherichia coli K12 mutants of R chemotype, with varying contents of major proteins, were studied with respect to serum-mediated killing. The mutants demonstrated a different susceptibility to serum lytic action. These results were related to phospholipid and fatty acid content, as well as different physico-chemical surface properties, such as outer membrane fluidity. Tests were carried out on all parameters considered in the literature to demonstrate the resistance to complement. Our results showed that in sensitive strains such as Salmonella strains SH6261, SH6378, SH5551, SH6017 and E. coli PC0479 tests taken alone were not sufficient to explain the resistance to complement. Therefore, complement susceptibility is probably determined by many factors influencing the microheterogeneity of the membrane system. PMID- 1857265 TI - A characterization study of a cell line (BS/BEK) from bovine embryo kidney. AB - A cell line (BS/BEK) which was obtained from bovine embryo kidney tissue, when studied at its 140th passage level it showed the following properties: 1. An epithelial-like morphology, possessing a heteroploid karyotype with a modal chromosome number ranging between 70 and 75 chromosomes. 2. It failed to produce tumors in mice and in hamster. 3. It was shown to be ready susceptible to the replication of several viral agents originated from a variety of animal species. 4. It was not contaminated by mycoplasma or other bacterial spp. PMID- 1857266 TI - Rectal lymphogranuloma venereum in a bisexual patient. AB - Rectal Lymphogranuloma venereum (LGV) due to Chlamydia trachomatis (Ct) serotype L2 is reported. LGV was isolated from the lymph node biopsy of a bisexual male and was cultured on McCoy cycloheximide treated-cells. Serological tests such as the Micro-immunofluorescent test and the indirect immunoperoxidase assay for Chlamydia trachomatis done on the patient's serum were positive with a titer of 1/200 and 1/256 respectively. Smears taken from the rectal discharge were stained by the direct immunoperoxidase assay and showed inclusion bodies with positive staining. The search for the origin source of infection as well as the diagnostic and follow-up strategy in the male and female partners is also discussed. PMID- 1857267 TI - HIV-1 infection and hematologic picture. AB - This review examines the wide spectrum of hematological abnormalities frequently observed in the peripheral blood and bone marrow of HIV-1 infected subjects. Several pathogenetic mechanisms have been implicated in the derangement of the hematopoietic system occurring during the course of HIV-1 infection: imbalance of the T-cell subpopulation (CD4/CD8 ratio), altered cytokine production by infected CD4+marrow cells, production of inhibitory factors by infected marrow stromal cells, antibody-mediated suppression of hematopoietic progenitors, direct infection of hematopoetic progenitors and/or precursors, and HIV-1 mediated suppression of CD34+ cell growth in the absence of a complete viral replication cycle. Each point is considered in the text, with particular attention to the mechanisms most likely to operate in the early stages of the syndrome. PMID- 1857268 TI - Post-traumatic stress disorder affects many young adults. PMID- 1857269 TI - Study shows success of AIDS prevention/anti-smoking campaigns. PMID- 1857270 TI - Liability reform in Michigan. The climate is right. PMID- 1857271 TI - Lansing attorney reacts to article on assisted suicide. PMID- 1857272 TI - Psychosocial changes during the first year of medical school. AB - The goal of this study was to assess psychosocial changes during the first year, on measures thought related to the long-term adjustment of medical students. Measures of self-esteem, health locus of control, hassles, uplifts, mood, and symptoms of stress were administered at the beginning and end of first year to 128 of 181 students. Self-esteem, powerful other locus of control, and uplifts decreased while hassles increased during the year. Positive mood decreased (joy, contentment, vigour, and affection) while negative mood increased (depression and hostility). Hassles at the beginning of the year were positively associated with health outcome at the beginning and end of the year. End-of-the-year first-year students appear to be worse off psychosocially than when they entered. With greater emphasis on health promotion and disease prevention and the adoption of other reforms in medical education, as suggested in the GPEP Report, medical students may learn to cope more effectively with stress as they pursue their medical education. PMID- 1857274 TI - Computer literacy among medical, nursing, dental and veterinary undergraduates. AB - Universities need to ensure that clinical undergraduates are educated in the use of computers in medical, nursing, dental and veterinary practice. We surveyed 875 students at Glasgow University to determine their computer literacy and attitudes to the use of computers. One in five students had not used a computer during the last year and 16% thought themselves to be a complete novice with computers. Medical students were more likely to have used a computer recently compared to dental and nursing students. For one in four students, the idea of working with a computer makes them anxious. Seventy per cent of students wanted more use of computers in the curriculum and 30% applied to attend an optional computing course in the summer. Although a third of students had not used a computer at school, the proportion had increased a little in recent years. At Glasgow University, changes need to be made to the undergraduate curriculum to teach students the use of computers in clinical practice. With a few exceptions, there is no reason to believe that this does not apply to other British universities. PMID- 1857273 TI - Perceived mistreatment and attitude change by graduating medical students: a retrospective study. AB - The goal of this study was to assess types and sources of perceived mistreatment, perceived attitude change, and academic performance of graduating medical students. A total of 87 of 143 (61%) students anonymously completed a mistreatment questionnaire, an attitude questionnaire, and questions about academic performance. The percentage of mistreatment was widespread (98.9%) with psychological mistreatment (shouting and humiliating) by residents/interns being most frequent. Over half of the students perceived sexual harassment, with women reporting greater harassment than men. There was a high incidence of disparaging remarks about doctors and medicine as a profession from a variety of sources. Increased mistreatment was positively associated with a perceived increase in cynicism. The potentially adverse effects of mistreatment on the individual student, the teacher-student relationship, and the doctor-patient relationship are discussed with recommendations for improving medical education. PMID- 1857275 TI - Medical problem-solving: an exploration of strategies. AB - In contrast to factual knowledge the reasoning processes of doctors in their attempts to clarify the patient's problem has been a somewhat neglected domain of study. The rise of experimental psychology, clinical decision analysis, and problem-based learning fostered studies in this area. Several studies from different viewpoints have been performed, leading to a more profound understanding of these processes. I approached the issue from a general physician viewpoint which reverted to the old distinction between deductive and inductive reasoning. Within a group of 68 participating doctors (family doctors and general physicians) the inductive method was exclusively employed. From this finding we conjecture that the inductive type of reasoning is the predominant style in the medical world. The consequences as attached to the overall utilization of the inductive method are far-reaching. Among others, process retracing as a feedback mechanism fails to function when it results from the intuitive nature of the (pattern-recognition) process. As a consequence we do not and can not know what we may learn from experience, good things as well as bad things. The inductive method is a method of practice and quick reaction, but it leaves us empty-handed as far as understanding and teaching are concerned. PMID- 1857276 TI - Self-planned experimentation (SPEX) practical classes in physiology. AB - A new form of undergraduate physiology practical experience is described. Students make their acquaintance with the physiological apparatus in the usual manner. At the end of the afternoon each group of four students is allocated an item of equipment with which to perform a true investigative experiment of their own choice, in their own time, the results of which are to be presented 2 weeks later by a randomly chosen member of the group. Students may investigate any question that can be answered using the resources available to them without endangering themselves or their subjects. Marks are awarded for the planning of the experiment (i.e. choice of controls, etc.), the correctness of graphical presentation of the results, the appropriateness of the statistical analysis, and for the discussion. There are no penalties for negative or unexpected results. PMID- 1857277 TI - The student diary survey: a method of monitoring hospital-based medical education. AB - A new system of allocating the Service Increment for Teaching (SIFT) has recently been introduced which, by its nature, encourages universities to be more explicit about their teaching requirements. A detailed study of the quantity of teaching received by Leicester clinical medical students was carried out using a student diary. This instrument enables a data base to be constructed which is useful for academic and resource allocation purposes. This information can also be used to estimate the teaching time in the different sites and the source of funding of the teaching staff and thereby provide insights into the 'knock-for-knock' system of informal cost-sharing between universities and the National Health Service. PMID- 1857278 TI - Reliability and feasibility of measuring medical interviewing skills: the revised Maastricht History-Taking and Advice Checklist. AB - Medical interviewing skills are integral to good medical care. In order to measure these skills an instrument has been developed, called the Maastricht History-Taking and Advice Checklist (MAAS). It has been studied with regard to interrater reliability and validity. In this study a revised version of the MAAS (MAAS-R), a check-list of concrete interview behaviour, has been investigated concerning feasibility and reliability for examination purposes. Audio-recordings were obtained of 24 doctors, each interviewing eight different standardized patients. The recordings were independently scored by three general practitioners trained in using the MAAS-R. The results of generalizability analysis, considering the influences of doctors, cases and raters, are encouraging. In order to overcome case-specificity feasible and reliable measurement can be accomplished with 8-10 cases in 2-21/2 hours of testing time, each case being scored by a different rater. Reliability improves considerably if assessment is restricted to basic interviewing skills. PMID- 1857280 TI - Responses to non-emergency questions in rural medicine: their usefulness to practice decisions. AB - This study reports the nature of non-emergency, day-to-day practice-related questions which arose in rural practice and were phoned in to a medical information system (MIS). The usefulness of these questions, and their responses, to clinical decision-making is outlined. Sixty-seven practitioners from 10 rural communities enrolled in the project. In response to each inquiry two or three articles were sent to the practitioner and to a consultant for validation. At the conclusion of the study the questions posed, and their responses, were examined. Forty-six per cent of the questions received were categorized as diagnostic; 30% as management; and 24% as therapeutic. Questions were classified using the ICD.9.CM. Those most frequently posed were in the nervous system/sense organs (13%), injury/poisoning (9%), and genito-urinary (9%) categories. Interviews with doctors and consultants were conducted to assess the usefulness of the service. Study findings suggest that an MIS can provide helpful information for improving daily aspects of clinical care, doctor-patient communication, administrative decision-making, and physician education. Practitioners, consultants, and medical librarians reported benefits from this service. PMID- 1857279 TI - Health care ethics teaching for medical students. AB - This paper describes an innovatory teaching programme in health care ethics for medical undergraduates. The general aims and objectives are outlined and the 1990 course is discussed specifically. The course has several unusual features, including the use of performers and the presentation of ethically based decisionmaking implements, which are highlighted. The course is evaluated. The 1990 results are encouraging. PMID- 1857281 TI - HIV/AIDS workshop for primary health care staff. AB - The purpose of this study was to develop and pilot a workshop to train general practitioners and other primary care workers to become competent in the primary, secondary and tertiary prevention of acquired immunodeficiency syndrome (AIDS). The development of the workshop took place at four venues in the South West Thames Region and involved 41 general practitioners and 33 primary care nurses. Questionnaire evaluation before and immediately after each workshop showed a significant improvement in participants' attitudes towards the prevention and management of human immunodeficiency virus (HIV) infection in general practice. We conclude that a suitably designed workshop can be effective in improving the attitudes of primary health care workers towards AIDS prevention and care. PMID- 1857282 TI - A postgraduate training course to prepare doctors for decision-making related to health authorities' computing services. AB - A training course which has been developed for doctors in public health medicine is described. Its underlying purpose was to create an appreciation of general management principles to ensure that resources would be directed to computing which supports patient care. This course could be adapted for computer training of experienced doctors in other branches of medicine. PMID- 1857283 TI - Male sexuality. 2. Psychiatric aspects of male sexual dysfunction. PMID- 1857284 TI - Common problems. Constipation. PMID- 1857285 TI - A survey of the visual acuity of Brisbane drivers. AB - OBJECTIVE: To conduct a survey of the visual acuity of a group of Brisbane Drivers. SETTING: The outpatient department of the Princess Alexandra Hospital, Brisbane. PARTICIPANTS: Five hundred and three subjects drawn from patients, visitors and staff attending the outpatient department on 10 working days from December 5 to December 16, 1988. MAIN OUTCOME MEASURES: Subjects' age, driver's licence details and driving history were gathered by questionnaire. Visual acuity was assessed with the aid of a Snellen chart. RESULTS: Nearly 6% of the survey group had visual acuity worse than 6/12; 15% had never had their eyes tested other than for licensing purposes; 21% stated that their last ophthalmic or optometric examination was more than five years previously; and 8% failed to meet the Queensland visual acuity requirements for their class of licence. CONCLUSIONS: The monocular driver is not detected by current licence testing procedures in Queensland. Many licence holders do not meet the present visual acuity criteria of the Queensland Department of Transport. PMID- 1857286 TI - The diagnosis of gestational diabetes. Ad Hoc Working Party. PMID- 1857287 TI - Vega testing in the diagnosis of allergic conditions. The Australian College of Allergy. AB - Vega testing (the Vega test method) is an unorthodox method of diagnosing allergic and other diseases. It has no established scientific basis and there are no controlled trials to support its usefulness. Vega testing may lead to inappropriate treatment and expense to the patient and community. PMID- 1857288 TI - Drug and alcohol use and abuse: historical and legal aspects. PMID- 1857289 TI - Our nursing homes. PMID- 1857290 TI - Beneficial effects of hyperbaric oxygen therapy in Nocardia brasiliensis soft tissue infection. AB - OBJECTIVE: To report the success of hyperbaric oxygen therapy in the treatment of Nocardia brasiliensis mycetoma. We believe this to be only the second report in the medical literature of hyperbaric oxygen therapy used in the therapy of nocardial disease. CLINICAL FEATURES: A 78-year-old man presented to a general hospital outpatient clinic after eight months with a painless swollen left foot. There was no significant medical history, no trauma had occurred, and no foreign body had been detected. The dorsum of the foot had a discharging sinus, from which N. brasiliensis was isolated. INTERVENTIONS: After unsuccessful treatment with surgical debridement and high-dose antibiotic therapy, hyperbaric oxygen therapy was administered in a multiplace recompression chamber (one hour of treatment at 1.8 atmospheres absolute followed by a 30 minute "ascent" to surface pressure). A total of 19 treatments were administered. OUTCOME: Successful healing of an N. brasiliensis mycetoma of the left foot. CONCLUSION: In this case of N. brasiliensis mycetoma involving the lower extremity, the conventional management of surgery and antibiotic therapy was unsuccessful, and only with the addition of hyperbaric oxygen therapy did clinical recovery occur. PMID- 1857291 TI - Management of massive verapamil overdose. AB - A 53-year-old man presented to hospital after an overdose (4.8 g) of verapamil. He developed profound bradycardia and hypotension, requiring treatment with calcium salts, dobutamine, isoprenaline and cardiac pacing. As calcium channel blockers are more widely used, self-poisoning will become more common. The effects, although serious, are self-limiting and recovery within 48 hours is the rule provided adequate support is given. PMID- 1857292 TI - Vinyl chloride related hepatic angiosarcoma in a polyvinyl chloride autoclave cleaner in Australia. AB - OBJECTIVE: To present the first case of vinyl chloride related hepatic angiosarcoma in Australia. CLINICAL FEATURES: A 51-year-old male caucasian former polyvinyl chloride autoclave cleaner in an Australian chemical plant developed hepatic angiosarcoma, presenting 15 years after his last exposure to vinyl chloride monomer. OUTCOME: He developed encephalopathy and died in oliguric renal failure 21 days after admission to hospital. CONCLUSION: Hepatic angiosarcoma may develop in other workers similarly exposed. PMID- 1857293 TI - Catfish trauma. PMID- 1857294 TI - Mycobacterium ulcerans infection in paradise. PMID- 1857295 TI - The media and suicide. PMID- 1857296 TI - Thrush in the ducts? PMID- 1857297 TI - Midwives' clinic. PMID- 1857298 TI - Portrait of a plague. PMID- 1857299 TI - Occupation-related leptospirosis in South Australia. PMID- 1857300 TI - North Coast cholesterol check campaign. PMID- 1857301 TI - Medical aspects of euthanasia. PMID- 1857302 TI - The "restless legs" syndrome. PMID- 1857303 TI - Management of prenatally diagnosed fetal abnormality. PMID- 1857304 TI - Problem drinkers. PMID- 1857305 TI - No association between DTP vaccination and SIDS. PMID- 1857306 TI - Necrotising arachnidism in Australia. PMID- 1857307 TI - Why are Australian peptic ulcer death rates rising? PMID- 1857308 TI - Developmentally disabled, doubly disadvantaged. PMID- 1857309 TI - Recertification of specialists. PMID- 1857310 TI - Dupuytren's contracture. PMID- 1857311 TI - Cervical cancer screening: a comparison of recruitment strategies among older women. AB - OBJECTIVE: To compare the effectiveness of different recruitment strategies in encouraging older women to have a Papanicolaou (Pap) test. DESIGN: A 2 x 2 factorial study. SETTING: Two rural areas of Victoria, Australia. PARTICIPANTS: A total of 10,620 persons aged between 40 and 69 years and designated as female on electoral lists. INTERVENTIONS: A personal letter of invitation and a community based campaign of 4 weeks' duration alone and in combination. A control group received no active intervention. OUTCOME MEASURE: The proportion of eligible women having a Pap test report issued by the Victorian Cytology Service during the 12 weeks after the intervention compared with the 12 weeks before the intervention, with an intervening two-week washout period. RESULTS: The odds ratio of an eligible woman being screened during the intervention period relative to the pre-intervention period was 3.00 for women who were exposed to the campaign and sent the letter of invitation (95% confidence interval, 2.38-3.77, P less than 0.001), 1.86 for women who were exposed to the campaign (95% confidence interval, 1.49-2.33, P less than 0.001), 1.61 for women who were sent the letter of invitation (95% confidence interval, 1.34-1.92, P less than 0.001). The baseline was a control group who received no active intervention. CONCLUSIONS: Both personal invitation letters and community-based campaigns are effective in recruiting women for Pap test screening. Combined strategies are more effective than single strategies. PMID- 1857312 TI - Obligatory nasal breathing: effects on snoring and sleep apnoea. AB - OBJECTIVE: To test the effects on snoring and sleep disordered breathing of a dental prosthesis (Snore-No-More) which is designed to decrease snoring by preventing mouth breathing during sleep. DESIGN: A crossover controlled trial. Each subject was studied on two nights a week apart. There was a control (no treatment) night and an experimental (treatment) night. The order of control and experimental nights was randomised. SETTING: The Royal Adelaide Hospital Sleep Laboratory. PARTICIPANTS: Fourteen male volunteers (age range, 36-59 years) were studied. All had a history of chronic snoring but denied other symptoms of obstructive sleep apnoea syndrome. INTERVENTIONS: On experimental nights subjects wore the dental prosthesis for the whole study period. On control nights no device was worn. MAIN OUTCOME MEASURES: Studies were conducted overnight during the subject's normal sleep period. The following measurements were made: (i) frequency and loudness of snores; (ii) frequency of disordered breathing events (apnoeas and hypopnoeas); (iii) mean and minimum arterial oxygen saturation while asleep; and (iv) sleep stages. RESULTS: The dental prosthesis did not change the mean frequency or mean intensity of snores. The number of sleep disordered breathing events per hour of sleep decreased by approximately one-third on experimental nights (mean +/- SEM events/h: control, 24.7 +/- 5.3; experimental, 16.1 +/- 3.3, P less than 0.05). Neither sleep architecture nor arterial oxygen saturation differed between control and experimental nights. CONCLUSION: Snores using the dental prosthesis Snore-No-More to produce obligatory nasal breathing are unlikely to experience clinical benefit. PMID- 1857313 TI - Prevalence of diabetes, hypertension and obesity at different levels of urbanisation in Vanuatu. AB - OBJECTIVE: To determine the prevalence of non-communicable disease, specifically hypertension, diabetes and obesity, amongst populations at different levels of urbanisation in Vanuatu, and to relate the frequency of these conditions to the modernisation of way of life. DESIGN: A cross-sectional population-based comparative study of indicative cluster samples. SETTING: Republic of Vanuatu (south-west Pacific). A relatively undeveloped malarious island country. PARTICIPANTS: Adult (aged greater than or equal to 20 years) Melanesian ni Vanuatu of both sexes. An occupation-based (civil servants) urban sample (n = 623) and area-based semi-rural (n = 349) and rural (n = 397) samples were employed. Response rates were 78%-92%. INTERVENTIONS: Cases detected were referred for assessment and treatment by local medical staff. MAIN OUTCOME MEASURES: Body mass index, triceps skinfold thickness, blood pressure, plasma glucose (fasting and 2 hours after 75 g glucose), plasma cholesterol and triglyceride levels. RESULTS: Modernity scores confirmed that the three locations represented different levels of acculturation. Prevalences of non-communicable disease were relatively low compared to other Pacific Island communities and industrialised countries. These conditions were nevertheless more common in the urban sample and least common in the rural sample. Non-communicable disease correlated positively with modernity scores and negatively with physical activity scores. Obesity correlated with blood pressure in the urban sample, and there was indirect evidence (urine sodium concentration) of higher salt intake with modernisation. Mean plasma cholesterol levels were lowest in the rural group. CONCLUSIONS: Prevalences of non-communicable disease are relatively low in Vanuatu, although rural-urban differentials are present, and likely to increase with continued development. The evidence presented is consistent with non communicable disease being related to the modernisation of way of life; specifically: decreased exercise, obesity, and dietary change. Preventive activities should commence now. PMID- 1857314 TI - Urticarial contact dermatitis in food handlers. AB - OBJECTIVE: To show that prick testing (using fresh samples of the food suspected from the patient's history) and not only patch testing is the appropriate investigation in selected cases of hand dermatitis in patients who spend considerable time handling foods (for example, catering workers, cooks). SETTING: The Contact and Occupational Dermatitis Clinic at the Skin and Cancer Foundation, a tertiary referral centre in Sydney. PATIENTS: Fourteen patients with hand dermatitis present for an average of 6.17 years referred by dermatologists and occupational health physicians. INTERVENTIONS: Patch and prick tests were performed for each patient. RESULT: In all patients prick tests identified the food allergens. Seafood was the most common allergen giving positive results in 10 patients. Patch tests did not identify any of the food allergens. Of the 14 patients nine were followed up and seven of these had been forced to change their career direction. CONCLUSION: Prick testing is the appropriate investigation in selected cases for the diagnosis of urticarial contact dermatitis in food handlers. PMID- 1857316 TI - [Compliance and non-compliance]. PMID- 1857315 TI - Principles behind practice. 6. Disease causation. The role of epidemiological evidence. AB - How can epidemiology contribute to understanding the cause of clinical disease? We discuss the nature of causality and the intrinsic limitations of all empirical science, including epidemiology, in establishing "proof" of causality. Our examples relate to eye disease: How the cause of blindness from retrolental fibroplasia was unravelled. How the congenital rubella syndrome was discovered as a cause of congenital cataract. How allopurinol was cleared from suspicion as a cause of cataract. PMID- 1857318 TI - [Poisoning caused bu mussels]. PMID- 1857317 TI - [PDGF, EGF and TGF-alpha. Promoters of cancer growth and wound healing]. PMID- 1857319 TI - [Hyperkinetic syndrome in childhood and adolescence. Diagnosis and therapy]. PMID- 1857320 TI - Present state of control of chemical and biological weapons. AB - The use of chemical and biological weapons in war is prohibited by the Geneva Protocol of 1925 and the Biological Weapons Convention of 1972. Currently a new Chemical Weapons Convention is being negotiated in the UN Conference on Disarmament in Geneva. When this Convention enters into force the production, stockpiling and retention of chemical weapons will be prohibited. The development of a body of international law will enable the verifiable destruction of weapons such as these, and should lead to a more general programme of disarmament. PMID- 1857321 TI - A social pathology of human conflict. AB - Cybernetics Academy Odobleja commemorates the name of the Romanian physician, psychologist and cybernetician Stefan Odobleja. Its Vice-President in France organized the First Seminar on Human Autonomy and Interdependence which was held in June 1988. This paper reviews some of the contributions to the Seminar. It also describes individual and social modes of human behaviour in terms of cybernetics and systems analysis, with a focus on group conflict. Some extracts from a provisional glossary of social cybernetics are appended. PMID- 1857322 TI - Medical peace research. PMID- 1857323 TI - Primary, secondary, and tertiary prevention of genocidal weapons. AB - For certain countries the availability of the technology and know-how has turned the nuclear weapons option, as well as the possession of chemical and bacteriological weapons, into a threatened reality of the present. Once a country embarks on a 'solution' such as this to its security problems, the countries in conflict with it are obliged to follow suit, thus accelerating the process of development and proliferation of similar weapons. Fear stimulates the creation of a spiral of false security that will inevitably result, if left to its 'natural' forces, in world-wide destruction. Nuclear war is examined here from an epidemiological viewpoint as a disease with two corresponding different possibilities: (a) the natural history of the disease, and (b) modifications produced by primary, secondary and tertiary prevention. Medical responsibility has no alternative but to work for the prevention of the incurable consequences of nuclear war. PMID- 1857324 TI - Verapamil prevents cerebral acidosis during moderate hypoxia and hypotension. AB - Carotid ligation and moderate hypoxia in rats causes an increase in the glucose metabolic rate in the caudate-putamen and more widespread reductions in pH. Pretreatment of animals with verapamil did not affect the abnormality of glucose metabolism but abolished the associated acidosis. These data suggest that calcium channel blockade may protect the brain from injury during hypoxic hypoxia by preventing the development of acidosis. PMID- 1857326 TI - Product review: the Coreco Oculus-500 imaging system. AB - Recent developments in computer imaging technology have brought about significant improvements in the display resolution and capabilities of desk-top imaging systems. The Coreco, Inc. Oculus-500 is a group of high resolution imaging boards for use with IBM-AT and compatible computers. The tested $8000 system consists of a 2 Mb interface board, display/controller board, driver, toolkit, and software interface package. With a display resolution of 1280 x 1024 @ 60 Hz non interlaced, the OC-500 offers excellent resolution. The accompanying software is being further developed by a responsive company, but can in places be tedious to use. However, the result of understanding the software is a system with superb capabilities. PMID- 1857327 TI - "These are the times that try men's souls" ... and their bodies. PMID- 1857325 TI - Vimentin mRNA expression increases after corticospinal axotomy in the adult hamster. AB - We examined changes in vimentin gene expression during Wallerian degeneration after corticospinal axotomy in the adult hamster. Vimentin, which is the product of a type III intermediate filament (IF) gene, is expressed in various cells of mesenchymal origin, including microvascular endothelial cells, microglia and developing astrocytes. While increases in vimentin protein have been observed after various types of central nervous system (CNS) injury, it is not known whether this increase is due to increased vimentin mRNA expression. There is also conflicting evidence as to which cells are expressing increased levels of vimentin. In the present study we used in situ hybridization and double-label immunofluorescence techniques to address these issues. A 35S-labeled vimentin cDNA probe was used for in situ hybridizations of brain stem sections obtained 2, 7 and 14 days after unilateral transection of the corticospinal tract in the caudal medulla of adult hamsters. Autoradiography showed that an increase in vimentin mRNA associated with the degenerating corticospinal tract occurred by 2 days after axotomy and that the levels remained elevated for at least 14 days. Immunoblotting and immunocytochemical studies indicated that vimentin protein levels were increased in the degenerating corticospinal tract. Double-label immunofluorescence revealed many vimentin-positive cells and processes that were also labeled with GFAP antibody. In addition, cells and processes that were vimentin-negative but GFAP-positive were also found in the degenerating tract. We suggest that the reactive cells which possessed both vimentin and GFAP were reactive astrocytes of astroblastic origin while those that expressed only GFAP were derived from mature astrocytes. Other vimentin-positive cells/processes did not label with anti-GFAP and thus were either microglial, endothelial or inflammatory cells. These results demonstrate that an increase in vimentin mRNA occurs during Wallerian degeneration after corticospinal axotomy and that this increase is likely to be due to contributions from more than one cell type. PMID- 1857328 TI - Rise in TB cases reported for 1990. PMID- 1857329 TI - Democracy is not a pretty sight. PMID- 1857330 TI - Dog bites. AB - Although our canine companions can provide us with many hours of unyielding love and faithfulness, it is important to remember that these same loving creatures inflict 500,000 to one million bites per year, accounting for one percent of all emergency room visits nationwide. Ten percent of these injuries require suturing, one to two percent require hospitalization, and approximately one-third of dog bite injuries cause lost time from work or school. The United States Postal Service spends more than $250,000 annually just for prevention and treatment of dog bite injuries involving letter carriers! Still think that adorable pooch is harmless? Read on. PMID- 1857331 TI - Physician peer review: have we gone far enough or too far? AB - The authors discuss the long history of physician peer review and offer insight on the process, while presenting factors that have lead to increased physician non-peer review. The question at hand--have we gone far enough ... or too far? PMID- 1857332 TI - Retroperitoneal liposarcoma: a case report. PMID- 1857333 TI - Congenital melanocytic nevi: update 1990. AB - The risks posed by congenital melanocytic nevi and best methods for their treatment have posed controversial questions. Here the authors review the most recent information and latest therapies for congenital nevi. PMID- 1857334 TI - Cloning and expression of an A1 adenosine receptor from rat brain. AB - We have used the polymerase chain reaction technique to selectively amplify guanine nucleotide-binding regulatory protein (G protein)-coupled receptor cDNA sequences from rat striatal mRNA, using sets of highly degenerate primers derived from transmembrane sequences of previously cloned G protein-coupled receptors. A novel cDNA fragment was identified, which exhibits considerable homology to various members of the G protein-coupled receptor family. This fragment was used to isolate a full-length cDNA from a rat striatal library. A 2.2-kilobase clone was obtained that encodes a protein of 326 amino acids with seven transmembrane domains, as predicted by hydropathy analysis. Stably transfected mouse A9-L cells and Chinese hamster ovary cells that expressed mRNA for this clone were screened with putative receptor ligands. Saturable and specific binding sites for the A1 adenosine antagonist [3H]-1,3-dipropyl-8-cyclopentylxanthine were identified on membranes from transfected cells. The rank order of potency and affinities of various adenosine agonist and antagonist ligands confirmed the identity of this cDNA clone as an A1 adenosine receptor. The high affinity binding of A1 adenosine agonists was shown to be sensitive to the nonhydrolyzable GTP analog guanylyl-5' imidodiphosphate. In adenylyl cyclase assays, adenosine agonists inhibited forskolin-stimulated cAMP production by greater than 50%, in a pharmacologically specific fashion. Northern blot and in situ hybridization analyses of receptor mRNA in brain tissues revealed two transcripts of 5.6 and 3.1 kilobases, both of which were abundant in cortex, cerebellum, hippocampus, and thalamus, with lower levels in olfactory bulb, striatum, mesencephalon, and retina. These regional distribution data are in good agreement with previous receptor autoradiographic studies involving the A1 adenosine receptor. We conclude that we have cloned a cDNA encoding an A1 adenosine receptor linked to the inhibition of adenylyl cyclase activity. PMID- 1857335 TI - Enantiomer/enantiomer interaction of (S)- and (R)-propafenone for cytochrome P450IID6-catalyzed 5-hydroxylation: in vitro evaluation of the mechanism. AB - Many drugs are used as racemates, and the enantiomers may differ in terms of pharmacological properties and disposition. Stereoselective disposition of the enantiomers can arise from metabolism of the enantiomers via different routes catalyzed by different enzymes. In contrast, the enantiomers may be metabolized by the same enzyme at different rates. In the latter case, the enantiomers can compete for this metabolic step, giving rise to the possibility of an enantiomer/enantiomer interaction. We have chosen the antiarrhythmic propafenone, for which in vivo data indicated an interaction between (S)- and (R)-propafenone, as a model substance to study the mechanism underlying that interaction in human liver microsomes. We used the cytochrome P450IID6-mediated 5-hydroxylation of propafenone as a model pathway, because this metabolic step constitutes the major route of biotransformation of propafenone. The Michaelis-Menten kinetics for 5 hydroxylation were determined after incubation of (R)- and (S)-propafenone and a pseudoracemate consisting of (S)-[2H4]propafenone and (R)-propafenone. Inhibition experiments were performed using (S)-[2H4]propafenone as an inhibitor of the 5 hydroxylation of (R)-propafenone, and vice versa. The kinetic model of mixed alternative substrates was used to simulate inhibition experiments. Experimental data were compared with those predicted by this model. We observed a substantial stereoselectivity after incubation of the individual enantiomers [(S) propafenone: Vmax, 10.2 pmol/micrograms/hr, and Km, 5.3 microM; (R)-propafenone: Vmax, 5.5 pmol/micrograms/hr, and Km, 3.0 microM]. In contrast, no substrate stereoselectivity was observed after incubation of the pseudoracemate [3.1 pmol/micrograms/hr for (S)-[2H4]propafenone and 3.3 pmol/micrograms/hr for (R) propafenone]. Application of the model revealed Ki values of 2.9 and 5.2 microM for the inhibition of 5-hydroxylation of (S)-[2H4]-propafenone by (R)-propafenone and for inhibition of 5-hydroxylation of (R)-propafenone by (S)-[2H4] propafenone, respectively. The predicted and the experimental data were in good agreement, and both indicated the mode of inhibition to be competitive. In conclusion, the enantiomers of propafenone interact with respect to 5 hydroxylation, with (R)-propafenone being a more potent inhibitor than the S enantiomer with respect to cytochrome P450IID6-mediated 5-hydroxylation. Because beta-blocking properties of propafenone reside in the S-enantiomer, inhibition of metabolism of this enantiomer by (R)-propafenone may have therapeutic consequences. PMID- 1857336 TI - Novel receptor site involved in enhancement of stimulus-induced acetylcholine, dopamine, and serotonin release. AB - The cognitive enhancer DuP 996 [3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2 one] and its structural analogs enhance the K(+)-stimulated release of acetylcholine, dopamine, and serotonin in brain slices, without effect on basal release. A novel receptor site labeled by [3H]DuP 996 has been identified. The [3H]DuP 996 binding site has a Kd of 19 nM and a Bmax of 102 fmol/mg of protein. Binding to this site is specific, saturable, reversible, and time, pH, and temperature dependent. Specific binding is decreased by treatment with trypsin and not affected by phospholipase C. Specific binding is inhibited by Ca2+ and increased by Mn2+ but not affected by Na+, K+, or Mg2+. The [3H]DuP 996 binding sites are heterogeneously distributed in brain, with striatum and hypothalamus having highest density and cerebellum lowest. The [3H]DuP 996 binding site does not belong to any known class of receptor site, because [3H]DuP 996 binding could not be displaced by a broad variety of standard pharmacological agents and neuropeptides. Physiological significance of this binding site is suggested by the excellent correlation between the binding affinity for this site and the potency to enhance K(+)-stimulated release of acetylcholine for a series of DuP 996 analogs. Ligands for this receptor site may have therapeutic potential for the treatment of cognitive deficits and neurodegenerative diseases. PMID- 1857337 TI - 5-Lipoxygenase-activating protein is the target of a quinoline class of leukotriene synthesis inhibitors. AB - An indole class of leukotriene synthesis inhibitors, exemplified by MK-886, which does not directly inhibit 5-lipoxygenase, has been shown to bind to an 18-kDa leukocyte membrane protein and to inhibit 5-lipoxygenase membrane translocation. It was demonstrated that the 18-kDa protein is necessary for the cellular activation of leukotriene synthesis and was named 5-lipoxygenase-activating protein (FLAP). We describe here a class of leukotriene synthesis inhibitors based on a quinoline structure, which is structurally distinct from MK-886. However, similar to MK-886, several quinolines are potent inhibitors of cellular leukotriene synthesis but are poor inhibitors of soluble 5-lipoxygenase. To determine whether FLAP is the protein target of leukotriene synthesis inhibitors of the quinoline class, we investigated the ability of these compounds to inhibit photoaffinity labeling of FLAP and to elute FLAP from indole affinity gels. The abilities of the quinoline inhibitors to interact with FLAP correlated well with their abilities to inhibit leukotriene synthesis in human polymorphonuclear leukocytes. L-674,573, a potent quinoline leukotriene synthesis inhibitor, inhibited indole photoaffinity labeling of FLAP in a concentration-dependent manner. In addition, L-674,573 selectively eluted FLAP from indole affinity gels, in contrast to L-671,480, a quinoline that was inactive as an inhibitor of leukotriene synthesis. When human leukocyte membranes were labeled with the indole photoaffinity probe [125I]L-669,083 and immunoprecipitated with a FLAP antibody, the labeling of FLAP was inhibited by L-674,573 but not by L-671,480. These results suggest a direct binding site for the quinoline leukotriene synthesis inhibitors on FLAP and provide further evidence for the essential role of FLAP in cellular leukotriene synthesis. PMID- 1857338 TI - Distribution of m2 muscarinic receptors in rat brain using antisera selective for m2 receptors. AB - The DNA fragment encoding the third intracellular loop of rat m2 muscarinic receptor was fused to the gene for staphylococcal Protein A. The resultant fusion protein, expressed in bacteria, was purified via IgG affinity chromatography and used as an antigen to raise a polyclonal antiserum. Chinese hamster ovary cells transfected with cDNA coding for a single muscarinic receptor subtype were used as tissue sources to screen antisera. The antiserum was shown to immunoprecipitate quantitatively (greater than 90%) m2 receptors but not to precipitate m1, m3, m4, or m5 receptors. Additionally, immunoprecipitation by m2 antiserum could be inhibited by protein containing the third intracellular loop of the m2 receptor. This selective m2 antiserum was then used to study the distribution and density of m2 receptors in rat brain and heart. In agreement with previous studies, m2 receptors were found to be abundant in heart and comprise at least 92% of the total muscarinic receptor density. Hindbrain, brain stem, and midbrain regions such as cerebellum (75%), pons/medulla (70%), and thalamus/hypothalamus (43%) are also enriched in m2 receptors. In contrast, forebrain regions contain markedly lower percentages of m2 receptors, with cortex expressing 20%, hippocampus 19%, striatum 12%, and olfactory tubercle 20% of the total receptor density. Although the density of m2 receptors expressed as a percentage of total varied considerably from brain region to brain region, the absolute density of these receptors appeared relatively uniform throughout the brain. This study demonstrates that a gene fusion system can be used for efficient antibody production. The use of similar fusion protein antisera directed against other subtypes of muscarinic receptors should prove useful in future studies on regulation, function, and structure of muscarinic receptors. PMID- 1857339 TI - Purification, immunochemical characterization, and immunohistochemical localization of rat hepatic aryl sulfotransferase IV. AB - Aryl sulfotransferases catalyze the formation of sulfuric acid esters from a diverse group of endogenous and xenobiotic organic chemicals. The isoenzyme of aryl sulfotransferase in livers of male Sprague-Dawley rats that exhibits the most varied substrate specificity is aryl sulfotransferase IV. A new method for the purification to homogeneity of aryl sulfotransferase IV was developed that, when compared with previously described procedures, provided a greater than 10 fold increase in total yield of enzyme/g of tissue. Homogeneous aryl sulfotransferase IV was used to prepare polyclonal antibodies in male New Zealand White rabbits. Results of immunochemical analyses demonstrated that these antibodies reacted with only a single protein in rat hepatic 100,000 x g supernatant fractions and, further, that the immunoreactive protein had the isoelectric point and subunit molecular mass characteristic of aryl sulfotransferase IV. Immunohistochemical analyses demonstrated that aryl sulfotransferase IV is present in hepatocytes throughout the liver, although centrilobular cells contain a significantly greater (p less than 0.01) amount of aryl sulfotransferase IV than do either midzonal or periportal cells, in which similar levels of the enzyme are found. PMID- 1857340 TI - Pyridine effects on expression and molecular regulation of the cytochrome P450IA gene subfamily. AB - The expression and molecular regulation of the cytochrome P450IA (P450IA) gene subfamily have been examined in rat hepatic tissue after treatment with pyridine. The microsomal ethoxyresorufin O-deethylase activity, which has been shown to be specific for the P450IA subfamily, was increased approximately 2- and 3.5-fold over control values at 10 and 16 hr, respectively, after a single dose of pyridine (100 mg/kg, intraperitoneally). P450IA1 protein expression was also elevated in a time-dependent manner, with a maximal increase in P450IA1 protein being seen at approximately 16 hr after a single dose of pyridine (100 mg/kg, intraperitoneally), as detected by immunoblot analysis using a monoclonal antibody that detects both P450IA1 and P450IA2. The immunochemically detectable level of P450IA1 decreased to that of control at 48 hr after treatment. Oligonucleotide probes specific for P450IA1 and P450IA2 mRNA were used in hybridization analyses to examine mRNA levels of P450IA1 and P450IA2, respectively. The level of P450IA1 mRNA in poly(A)+ mRNA was increased approximately 3- and 2-fold at 5 and 12 hr, respectively, after a single injection of pyridine, as evidenced by both slot blot and Northern blot analyses. A lesser increase (approximately 1.5-2-fold) in P450IA2 mRNA was also seen at 5 and 12 hr after treatment. The P450IA1 and P450IA2 mRNA levels returned to control values at 48 hr after pyridine administration. These results were compared with those produced by 3-methylcholanthrene at 5 hr after treatment. A multiplex polymerase chain reaction assay was also used to monitor simultaneously the changes in P450IA1, P450IA2, and P450IIE1 mRNA levels, and the results showed induction of P450IA1, in agreement with the results of slot and Northern blot analyses. In summary, metabolic activity assays, immunochemical detection, and Northern and slot blot analyses provide evidence to support the conclusion that pyridine modulates the expression of the P450IA gene subfamily and does so by elevating P450IA1 and P450IA2 mRNAs, through either transcriptional activation or increased mRNA stabilization. These results are in sharp contrast to P450IIE1 induction by pyridine, which appears to proceed through increased translational efficiency. Thus, pyridine, which is present in tobacco and tobacco smoke, is capable of simultaneously elevating multiple forms of P450 that are active in carcinogen metabolism. PMID- 1857341 TI - Neuronal cytochrome P450IID1 (debrisoquine/sparteine-type): potent inhibition of activity by (-)-cocaine and nucleotide sequence identity to human hepatic P450 gene CYP2D6. AB - Catalytic, pharmacological, and molecular criteria have been used to identify cytochrome P450IID1 in mammalian brain (enzyme, P450IID; gene, CYP2D). Sparteine metabolism in canine striatal membranes was shown to be inhibited in a concentration-dependent and stereoselective manner by quinidine (Ki, approximately 51 nM), quinine (Ki, approximately 5.9 microM), and various other known substrates and inhibitors of hepatic P450IID1 activity. In addition, canine striatal P450IID1 was inhibited with high affinity by dopamine uptake blockers, such as (-)-cocaine (Ki, approximately 74 nM), d-amphetamine (Ki, approximately 4.5 microM), and methylphenidate (Ki, approximately 15 microM). Inhibitory constants (Ki) of numerous compounds for inhibition of sparteine metabolism in canine striatal membranes correlated well with (a) Ki values observed in human liver microsomes (r = 0.95), (b) [3H]GBR-12935 binding to P450IID1 in canine striatal membranes (r = 0.85), and (c) the inhibition (IC50) of sparteine metabolism in HepG2 cells expressing human CYP2D6 cDNA (r = 0.93). Moreover, antibodies raised against rat hepatic enzyme inhibited, in a concentration dependent manner, sparteine metabolism in canine striatal membranes. Enzymatic activity was unevenly distributed throughout the canine brain and ranged from 0.5 to 21 pmol/mg of protein/hr in cerebellum and supraorbital cortex, respectively, with the striatum displaying moderate levels of activity (8 pmol/mg of protein/hr). The polymerase chain reaction was used to amplify cDNA from a human caudate lambda gt11 library encoding exons 6-9 of the human CYP2D6 gene, which revealed, upon sequencing, 100% nucleic acid sequence identity. These data indicate that P450IID1 is expressed centrally and is similar, at the functional and molecular levels, to the human hepatic P450IID1 enzyme. Because the debrisoquine/sparteine mono-oxygenase is a polymorphic enzyme, in which 5-10% of caucasians are deficient in metabolism of various drugs, a genetic difference in human brain metabolism of P450IID1 substrates may possibly lead to differences in drug response and toxicity. PMID- 1857342 TI - Separation of human liver microsomal tolbutamide hydroxylase and (S)-mephenytoin 4'-hydroxylase cytochrome P-450 enzymes. AB - Purification and immunoinhibition studies have suggested that the hydroxylations of (S)-mephenytoin and tolbutamide are catalyzed by rather similar forms of human liver cytochrome P-450 (P-450). However, the two activities are not well correlated in vivo; sulfaphenzaole is a selective inhibitor of tolbutamide hydroxylation, and expression of P-450 2C10 cDNA in yeast yields a protein that hydroxylates tolbutamide but not (S)-mephenytoin. The P-450 2C8, 2C9, and 2C10 cDNAs have all been isolated, and their sequences are known to be closely related (greater than 80%). Highly sensitive radiochromatographic assays were set up, and tolbutamide and (S)-mephenytoin hydroxylation activities were monitored during chromatography of human liver microsomal fractions. The two activities could be separated by chromatography, and proteins were purified to near-homogeneity that catalyzed either tolbutamide hydroxylation (P-450TB) or (S)-mephenytoin 4' hydroxylation (P-450MP) but not both. Approximately 16 and 45% of the primary sequences of P-450TB and P-450MP, respectively, were determined by analysis of the tryptic peptides. The sequences of the P-450TB peptides matched those predicted by the P-450 2C9 and 2C10 cDNAs exactly; the P-450MP peptides showed two mismatches (of 219 residues) with the P-450 2C10 sequence. Proteins with the P-450 2C10 and P-450 2C9 sequences were expressed in Saccharomyces cerevisiae grown under different nutritional conditions, and both were found to be proficient in the hydroxylation of tolbutamide but not (S)-mephenytoin. We conclude, on the basis of this and previous work, that 1) P-450s 2C8, 2C9, and 2C10 all catalyze the hydroxylation of tolbutamide and 2) the protein involved in polymorphic (S)-mephenytoin 4'-hydroxylation is closely related to but distinct from P-450 2C8, 2C9, and 2C10. PMID- 1857343 TI - Sex-related differences in the expression of chick enterocyte butyrylcholinesterase during embryonic and post-hatching development. AB - The butyrylcholinesterase activity of chick enterocytes was studied from day 15 in ovo up to day 90 after hatching. The activities detected in both sexes at the level of jejuno-ileum change in a parallel manner, but the activity is always higher in the female than in the male during embryonic development. After hatching, the differences are less apparent although the study of the enzyme distribution along the intestine showed sex-related variations, mainly at the level of the anterior and middle parts of jejuno-ileum in the young adult. Analysis of butyrylcholinesterase by sucrose gradient centrifugation allowed to identify two globular soluble species (G1 and G4 forms). The G4/(G1 + G4) ratio decreases during the development but this variation in the female does not parallel that observed in the male. Besides, the molecular form distribution along the intestine, studied after hatching, differs according to the sex. Taken together our results lead to hypothesize that the ontogeny and the regulation of the chick enterocyte butyrylcholinesterase depend on hormones. PMID- 1857344 TI - Characterization of overt carnitine palmitoyltransferase in rat platelets; involvement of insulin on its regulation. AB - Saponin-permeabilization (30 micrograms/ml) of the platelet plasma membrane, which enables access of added compounds to mitochondrial overt carnitine palmitoyltransferase (CPT I), was applied to allow the rapid determination of CPT I activity in situ. The effects of diabetes and short-term incubation with insulin in vitro on the kinetic parameters and malonyl-CoA sensitivity of CPT I were also studied in rat platelets. CPT I exhibited ordinary Michaelis-Menten kinetics when platelets were incubated with palmitoyl-CoA. Malonyl-CoA showed an I50 (concentration giving 50% inhibition of CPT activity) of 0.92 +/- 0.11 microM in permeabilized platelets. Platelets obtained from diabetic rats (induced by streptozotocin injection) exhibited an increased Vmax and I50 for malonyl-CoA, and an unaltered Km for palmitoyl-CoA. In contrast, preincubation of platelets prepared from both fed control rats and diabetic rats with insulin (100 and 150 microU/ml) led to a decrease in enzyme activity when assayed with 75 microM palmitoyl-CoA and 0.5 mM L-carnitine as substrates. These in vivo and in vitro results suggested that insulin directly modulated rat platelet CPT I activity, as it does in the liver. PMID- 1857345 TI - Oxygen-derived free radicals producing activity and survival of activated polymorphonuclear leukocytes. AB - Activation of polymorphonuclear (PMN) leukocytes is known to generate oxygen free radicals (OFR). However the fate of activated PMN leukocytes is not known. We investigated the OFR producing (chemiluminescence) activity and the survival of the activated PMN leukocytes. The study was divided into two groups. Group I, In vivo study (n = 7): zymosan (8.4 mg/kg) was administered intravenously in the anesthetized dogs and the blood samples were collected before and after 5, 15, 30, 60 and 120 min of zymosan administration. This group represents the in vivo pre-stimulated PMN leukocytes; Group II, In vitro study (n = 7): the blood were collected from dogs and further divided into two groups. Group A (n = 7): non stimulated, without any added zymosan and group B (n = 7): zymosan was added to stimulate PMN leukocytes. Blood samples from group A and B were also collected at various time intervals similar to in vivo studies. Oxygen free radical producing activity of PMN leukocytes was monitored by measuring luminol-dependent chemiluminescence (CL). Opsonized zymosan was used to activate PMN leukocytes. The studies in which the PMN leukocytes were stimulated in in vivo, both oxygen derived free radicals and superoxide dismutase (SOD) inhibitable oxygen free radical CL decreased significantly for 60 min and tended to reach thereafter to the pre-stimulated values. The resting chemiluminescence (chemiluminescence without zymosan stimulation in the assay medium) increased significantly for 15 min reaching to pre-stimulated values at 30 min and thereafter. In in vitro studies, oxygen derived free radicals CL of pre-stimulated PMN leukocytes (Group B) was depressed for the whole duration of investigation while SOD inhibitable CL was depressed for only 60 min. There was approximately a two-fold increase in the resting CL within 5 min of PMN leukocyte activation and it remained high for the whole duration of study. The chemiluminescence of non-stimulated PMN leukocytes in vitro (group A) remained practically normal throughout the period of observation. In in vivo studies, total white blood cells (WBC) and PMN leukocyte counts decreased initially and tended to approach towards pre-stimulated values at the end of the protocol. There were no changes in these counts in in vitro studies. These results indicate that the capacity to generate OFR is decreased in the in vivo and in vitro pre-stimulated PMN leukocytes. However this activity recovers with time. This study also suggests that the activated PMN leukocytes are not destroyed. PMID- 1857348 TI - Thyroid hormone effects on the State IV proton motive force in rat liver mitochondria. AB - In order to further investigate the mechanisms regulating the control of mitochondrial respiration by thyroid hormone, the proton motive force was measured during State IV respiration in liver mitochondria isolated from euthyroid, hyperthyroid, hypothyroid and T3-treated hypothyroid rats. The proton motive force was significantly higher in the hyperthyroid group due to an increased delta pH. The proton motive force of hypothyroid mitochondria was lower than controls due to a decreased membrane potential. The proton motive force for the T3-treated hypothyroid group did not differ from the euthyroid group due to negating changes in the pH gradient and the membrane potential. The intramitochondrial volume was decreased in the hyperthyroid group and unchanged in the other groups. The results indicate that the thyroid status alters the proton motive force in State IV through individual changes in the pH and membrane potential components of the force. The component that changes in hyperthyroid mitochondria is different from that changing in hypothyroid mitochondria. PMID- 1857346 TI - Free radicals involvement in neurological porphyrias and lead poisoning. AB - Porphyrias are inherited and acquired diseases of erythroid or hepatic origin, in which there are defects in specific enzymes of the heme biosynthetic pathway. In patients with intermittent acute porphyria and lead poisoning the erythrocytic activities of superoxide dismutase and glutathione peroxidase are reported to be increased. Our studies demonstrated that d-aminolevulinic acid, a heme precursor accumulated in both diseases, undergoes enolization at pH less than 7.0 before it autoxidizes. The autoxidation of d-aminolevulinic acid, in the presence or absence of oxyhemoglobin has been proposed as a source of oxy and carbon-centred radicals in the cells of intermittent acute porphyria and saturnism carriers. Thus, the increased levels of antioxidant enzymes can be viewed as an intracellular response against the deleterious effects of these extremely reactive species. PMID- 1857347 TI - Role of sulfhydryl groups in phospholipid methylation reactions of cardiac sarcolemma. AB - The effect of reagents that modify sulfur-containing amino acid residues in the phosphatidylethanolamine N-methyltransferase was studied in the isolated rat cardiac sarcolemma by employing S-adenosyl-L-[methyl-3H]methionine as a methyl donor. Dithiothreitol protected the sulfhydryl groups in the membrane and caused a concentration- and time-dependent increase of phospholipid N-methylation at three different catalytic sites. This stimulation was highest (9-fold) in the presence of 1 mM MgCl2 and 0.1 microM S-adenosyl-L-[methyl-3H]methionine at pH 8.0 (catalytic site I), and was associated with an enhancement of Vmax without changes in Km for the methyl donor. Thiol glutathione was less stimulatory than dithiothreitol; glutathione disulfide inhibited the phosphatidylethanolamine N methylation by 50%. The alkylating reagents, N-ethylmaleimide and methylmethanethiosulfonate, inhibited the N-methylation with IC50 of 6.9 and 14.1 microM, respectively; this inhibition was prevented by 1 mM dithiothreitol. These results indicate a critical role of sulfhydryl groups for the activity of the cardiac sarcolemmal phosphatidylethanolamine N-methyltransferase and suggest that this enzyme system in cardiac sarcolemma may be controlled by the glutathione/glutathione disulfide redox state in the cell. PMID- 1857350 TI - Theoretical analysis of the accuracy of calibrated immunoassays for measuring antibody concentration. AB - The accuracy of calibrated immunoassays for measuring antibody concentration was analysed from a theoretical perspective. The study shows that there are theoretical limits on the accuracy of antibody immunoassays, which are determined by the affinity of the standard and unknown antibodies and the conditions chosen for the assay. As a result of these limits, calibration of an immunoassay with a standard antibody does not automatically ensure accurate measurements of antibody concentration. Extremely large errors may develop in affinity-dependent assays when the affinities of the standard and unknown antibodies are different. Assay conditions and the affinity of the standardizing antibody must be chosen carefully to measure antibody concentration accurately. PMID- 1857349 TI - Analysis of the H-2Kbm8 mutant: correlation of structure with function. AB - The gene for H-2K class I major histocompatibility antigen on the bm8 variant was cloned and the DNA sequence compared with the parental gene. Sequence analysis demonstrated that seven nucleotides were changed with respect to the parental gene sequence spanning 24 nucleotides. These changes represent an alteration of four amino acids from the parent protein. As this mutation occurred in a single generation, a potential donor gene for such a complex mutation was suggested and identified. The Q4 gene class I-like molecule has a stretch of 95 nucleotides of identity in the region of the bm8 mutation. Genomic Southern analysis of the mutant and parental DNA with a gene-specific oligonucleotide demonstrated that the potential donor gene Q4 is a likely candidate sequence for such an event. The amino acid alterations for the H-2Kbm8 mutation are discussed in consideration of hte three-dimensional structure of the characterized human class I glycoprotein. PMID- 1857351 TI - Identification and characterization of important allergens from mugwort pollen by IEF, SDS-PAGE and immunoblotting. AB - Mugwort (Artemisia vulgaris L.) pollen allergens, separated by SDS-PAGE or IEF, were identified after transfer to NCM by incubation with a panel of sera from 16 patients with clinical mugwort pollen allergy, followed by [125I]anti-IgE and autoradiography. Of the at least 23 components separated by SDS-PAGE in a 15% polyacrylamide gel, at least 15 components with mol. wts 12,000-100,000 bound IgE from the panel of patient sera. A component of mol. wt 22,000 bound IgE from at least 94% of the patient sera tested and for all but three sera this component also bound the greatest quantity of IgE. Five other components with mol. wts 12,000, 17,000, 29,000, 39,000 and 42,000 bound IgE from 75-94% of the patient sera. After separation by IEF, at least 28 protein bands were detected in the pI region 3.5-7.2 and at least seven bands were found in the region 8.6-9.3. At least 11 bands in the pI range 4.2-7.3 and at least five bands in the pI region 8.5-9.2 bound IgE from the panel of patient sera. The most intense radiostaining was observed with a component having a pI of 4.35, which bound IgE from 31% of the patient sera. Immunoblotting of the SDS-PAGE and IEF gels using specific rabbit antisera and human sera against three important mugwort pollen allergens, denoted Ag 9, Ag 12 and Ag 13, was performed to determine the mol. wt and pI of these allergens which had earlier only been identified in CIE/CRIE. The results revealed that Ag 13 had a mol. wt of 61,000 and a pI of 4.35, Ag 12 had a mol. wt of 22,000 and AG 9 had pIs in the region 4.55-5.55 (six isoforms). Ag 9 did not bind IgE after SDS-PAGE and was thus not identified in the SDS-PAGE pattern, and Ag 12 failed to be detected in the NCM after transfer from IEF gels. By crossed immunoelectrofocusing, Ag 12 was found to consist of several isoforms predominantly located in the pI region 3.5-5.1. The immunoblotting analysis also revealed that the glycoprotein allergen Art v II was not detected after transfer from either SDS-PAGE or IEF gels. In conclusion, immunoblotting analysis of SDS PAGE and IEF gels are useful methods for characterization of mugwort pollen extract, but it should be noted that some important allergens which are easily identified in CIE/CRIE may fail to be detected by these methods. PMID- 1857352 TI - Immunogenicity of free histones and of histones complexed with RNA. AB - Histone antibodies have been obtained by immunizing rabbits with histones H1, H2A, H2B, H3, H4 and triacetylated H4, uncomplexed to RNA. The reactivity of these antibodies was investigated by ELISA using as antigen isolated histones and chromatin as well as thirty-five different synthetic peptides covering the entire sequence of the four core histones, two peptides of H1 and two acetylated peptides of H4. The binding of these antibodies to histones was also measured in immunoblotting and in microcomplement fixation (MCF) tests. In parallel experiments using the same assays the various antigens were tested with antisera raised against histones complexed with RNA. Antibodies induced in the absence of RNA did not react with histones in MCF tests nor with chromatin in ELISA but reacted with the histones in ELISA, although the antibody titers were somewhat lower than in the case of antisera to histone-RNA complexes. Antibodies to RNA histone complexes reacted with histones in both ELISA and MCF tests. When they were tested with peptide-coated microtiter plates in a direct binding ELISA format, antibodies induced with uncomplexed histones recognized very few fragments which were mainly located in the N- and C-terminal ends of the histones. PMID- 1857353 TI - Arthritis of the lumbar spine. AB - Many types of arthritis can disturb the normal lumbar anatomy. This review intentionally omits many endocrine, metabolic, and genetic disorders that ultimately lead to breakdown of cartilage. Osteoarthritis remains the most common cause of sustained back pain as well as one of the most compensable disabilities in the United States. As so many other authors have noted, more scientific investigation is needed, and funding is imperative to effect significant changes. PMID- 1857354 TI - Lumbar stenosis. AB - Lumbar stenosis continues to be inadequately appreciated as a major cause of sciatica, neurogenic claudication, and cauda equina syndrome. Review of the nineteenth-century medical literature reveals articles on narrow canal syndrome in achondroplastic dwarfs; connection to the clinical presentation of developmental spinal stenosis awaited the middle decades of the twentieth century. Appropriate neurosurgical intervention has evolved with a better understanding of the pathophysiologic changes that take place with this disorder and the introduction of myelography, computerized tomography, and magnetic resonance imaging. PMID- 1857355 TI - Synovial cysts of the lumbar facet joint. AB - A study of 42 synovial cysts arising from the lumbar facet joint is presented. Intraspinal cysts caused radicular pain and cauda equina syndrome in 11 patients. In a series of 1,400 lumbar laminotomies for a herniated disk, 31 incidental nodules arising from the exposed facet as paraarticular masses were found and excised. The limited number of reports in the orthopedic and neurosurgical literature has not dealt adequately with the etiology or incidence of these benign lesions. The neuroradiologic appearance and histopathologic findings are briefly discussed. PMID- 1857356 TI - Preoperative and postoperative neuroradiologic evaluation of lumbar disk herniation. AB - Three hundred and forty patients with signs and symptoms of lumbar disk disease were evaluated preoperatively by conventional X-rays, computed tomography, and 2.0 Tesla magnetic resonance imaging (MRI). High-resolution T2 weighted MRI provided a truly noninvasive myelogram. The operative findings were predicted by and correlated with the neuroradiologic studies. High-resolution MRI with intravenous gadolinium-DTPA (Magnevist, Berlex) has been particularly useful in evaluating patients with a history of prior disk surgery and patients who were not relieved of pain by lumbar diskectomy. PMID- 1857357 TI - Role of laminectomy in lumbar disk herniation. AB - A personal view of the role of laminectomy in lumbar disk herniation is presented. The phenomena of the true herniated nucleus pulposus and the asymptomatic bulging degenerative disk are discussed in relation to clinical presentation, neuroradiologic studies, and surgical findings. Microscopic technique and so-called less invasive procedures are also evaluated. PMID- 1857358 TI - Microdiskectomy--myth, mania, or milestone? An 18-year surgical adventure. AB - The term "microdiskectomy" in the medical literature defines absolutely no surgical parameters or specific techniques for the treatment of the herniated nucleus pulposus. I attempt to clarify frequently used slang and to design a logical mental and microsurgical approach to the problem of lumbar disk herniations. The rigid surgical technique of microlumbar diskectomy is closely examined. PMID- 1857359 TI - Lumbar diskectomy under the operating microscope. PMID- 1857360 TI - Automated percutaneous lumbar diskectomy. AB - Automated percutaneous lumbar diskectomy was introduced in 1985. Development of this technique was instigated by the general trend in medicine toward less invasive procedures. Technique, indications, patient selection, and a review of the current literature are presented. Cumulative data indicate that the procedure has the least potential to do harm compared to open operations for treating lumbar disk herniations. PMID- 1857361 TI - Arthroscopic microdiskectomy. AB - Arthroscopic microdiskectomy through a posterolateral approach has opened a new window of opportunity in the treatment of lumbar disk disorders. Radiographic identification of the triangular working zone has permitted the safe introduction of instruments with an external diameter of 7-8 mm into the intervertebral disk. The technique allows not only evacuation and decompression of contained herniated disks, but also the introduction of instruments for decortication of the vertebral plates and bone grafting for percutaneous interbody fusion. Endoscopic laser nucleolysis, currently under investigation, may also enhance existing technological achievement in the field of minimal-intervention spinal surgery. Arthroscopic microdiskectomy has proven to be safe, effective, and cost efficient. In properly selected patients, satisfactory results of approximately 85% have been realized. PMID- 1857362 TI - Minilaminotomy as an alternative to laminectomy or microdiskectomy: ten years' experience. AB - Minilaminotomy as an alternative to microdiskectomy or standard laminectomy has been performed at two community hospitals on 1000 patients over a period of 10 years. The operative technique, employing simple prone positioning, a 4-cm incision, standard instruments, X-ray guidance, a fiberoptic head light, and 4.5 x binocular loupes, has not changed since 1986, when the initial series of 200 cases was published. The overall results in 800 additional patients continued to compare favorably to all reported series of microdiskectomy: minimal blood loss, less narcotic requirement, fewer days in the hospital, earlier return to normal activity, no wound infection, and low rate of second surgery. PMID- 1857363 TI - Spinal instrumentation for degenerative disease of the lumbar spine. AB - Instrumentation for spinal implant is currently changing more rapidly than at any previous period in its 100-year history. At present, the most common indication for spinal instrumentation is degenerative disease of the lumbar spine, which can be roughly categorized as of three kinds: herniated lumbar disks, spondylolisthesis, and spinal stenosis. The literature on indications for arthrodesis is reviewed. A brief summary of the approach and type of instrumentation available for the lumbar spine is presented. PMID- 1857364 TI - The risk of wound infection in lumbar disk surgery. AB - A number of questions were left unanswered by the empirical success of a 15-year regimen of prophylactic antibiotics in preventing postoperative sepsis at three community hospitals. Although intraoperative cephalosporins have eliminated the morbidity of primary wound infection, the susceptibility to these agents of nosocomial flora has fallen considerably. The principles of antimicrobial prophylaxis have been established, but the debate over the importance of meticulous aseptic technique versus prophylactic antibiotics goes on. We investigated the microbiologic factors in lumbar disk surgery at Nyack Hospital over one year to study (a) potential sources of random contamination, (b) the flora of the operating room, and (c) the efficacy of various aspects of antiseptic routine. PMID- 1857365 TI - Causes of failure of surgery on the lumbar spine: ten-year follow-up. AB - A decade has passed since the primary factors in failures of surgery on the lumbar spine were identified, and the entity is still an expensive, disabling reality for too many patients. The incidence of failure has significantly decreased due to better practices as well as advances in the technology of surgical diagnostic studies and better means of conservative care. The author would like to join his colleagues in acknowledging the many contributions of Dr. Leonard Malis throughout his career toward improving the quality of patient care and helping avoid failure of back surgery in all patients. PMID- 1857366 TI - Lumbar disk disease: controversies in neurosurgery. PMID- 1857367 TI - Lumbar disk disease: controversies in neurosurgery. PMID- 1857368 TI - [A new system of selecting yeast mutants with disrupted genetic recombination processes]. AB - A new convenient system for isolation of the yeast mutants deficient in the genetical recombination is proposed. The chimeric plasmids constructed to carry the noncomplimenting mutant copy of the yeast ADE2 gene and different selectable yeast markers (LEU2 or TRP1 genes) are the basis for the system. Interplasmid intragenic recombination of ADE2 gene alleles in yeast cells transformed by two chimeric plasmids results in appearance of the secondary white prototrophic clones covering the primary red colony. The number of the clones reflects the recombination processes and is subject to an easy visual control. The proposed technique allows one to reveal both hypo and hyperrecombination mutants. Crossover or the gene conversion events can be distinguished by the simple genetical analysis of the secondary clones. The collection of mutants deficient in the genetical recombination has been obtained by the proposed technique. PMID- 1857369 TI - [The effect of Yersinia pestis EV76 6 MD plasmid on the composition of outer membrane proteins of Yersinia pseudotuberculosis YPIII]. AB - On the basis of Yersinia pseudotuberculosis strain YPIII the isogenic variants containing the different combinations of 47 Md plasmids from Yersinia pestis or Yersinia pseudotuberculosis cells with the 6 Md pYP plasmid from Yersinia pestis EV (intact or having impaired the pla gene determining the synthesis of plasmocoagulase). The degradation of the secreted proteins encoded by the 47 Md plasmids of Yersinia pestis and Yersinia pseudotuberculosis in the cells harbouring the 6Md pYP plasmid has been registered. Yersinia pseudotuberculosis strain YPIII carrying its own 47Md and pYP plasmids also contained no YOP1 protein, in contract to the parent strain. The damage of the pla gene eliminated the destructive effect on the outer membrane proteins. Imposition of the 47Md and 6Md plasmids from Yersinia pestis in Yersinia pseudotuberculosis cells may be used for obtaining and study of the physiological role of low molecular mass proteins resulting from proteolysis of proteins encoded by the 47Md virulence plasmid of Yersinia. PMID- 1857370 TI - [Detection of virulence markers in clinical strains of Yersinia]. AB - The dispersion of plasmid pYV associated virulence markers in 474 Yersinia strains isolated from people has been studied. The ability to autoagglutination, calcium dependence of growth and the specific antigens were identified in 157 strains of traditionally pathogenic Yersinia enterocolitica serovars 03, 09, Yersinia pseudotuberculosis serovar I. They were not found in 223 strains of other 12 serovars of Yersinia enterocolitica, in 40 strains of Yersinia frederiksenii, Yersinia kristensenii, Yersinia intermedia. The proportion of virulent clones in the population of Yersinia is noted to depend on the conditions of its existence in vivo or in vitro. Identification of virulence markers is acknowledged to be expedient in epidemiological and ethiological estimation of the role of isolated Yersinia strains. PMID- 1857371 TI - [Marburg virus: the first determined nucleotide sequence of two genes]. AB - The preparations of purified Marburg virus were isolated from blood plasma of infected guinea pigs and characterized. Viral RNA was extracted from the virions. The cDNA was synthesized on the isolated RNA matrix by the reverse transcriptase with the use of dissipated priming. The obtained cDNA was inserted into the plasmid pBR322 by the connector technique and the resulting recombinant plasmids were cloned in Escherichia coli cells. The specific clones selected by molecular hybridization method were analyzed by the restriction mapping and cross hybridization. Four overlapping cDNA clones were found and the virus specific 5012 bp fragment of the viral genome was sequenced. Three open reading frames were found and the preliminary analysis of the coded amino acid sequence and corresponding genes was fulfilled. PMID- 1857372 TI - [The effect of a plague pathogen plasmid on lethality and immunogenicity]. AB - On the model of Yersinia transconjugants (Yersinia pestis, Yersinia pseudotuberculosis, Yersinia enterocolitica) carrying the conjugative cointegrates containing the 47 and 65 Md plasmids from Yersinia pestis the data were obtained on the different affects of the latter plasmids on the lethality and immunogenicity conferred by the host bacterial cells. The plasmid effects were drastically different during bacterial infection in mice or guinea pigs. The possibility of appearance of the recombinant Yersinia in natural epizootic foci of plague and suggestions on their regulating role are discussed. PMID- 1857373 TI - [The effect of the bacterial genome on the expression and behavior of the plasmid determining the Ca2+-dependence of the plague pathogen]. AB - The conjugative cointegrate containing the 47 Md plasmid of Yersinia pestis has been transferred into the strains of the different Yersinia (Yersinia pestis, Yersinia pseudotuberculosis, Yersinia enterocolitica) and Escherichia coli CA. There appeared in the populations of recombinant Yersinia under the conditions of Ca2+ deficit at 37 degrees C the cells coming into the stasis stage or dying. It was shown on the model of Yersinia enterocolitica that bacterial lethality might be prevented by exclusion of the sheep blood from Ca2+ deficient medium. Ca(2+) dependence was not expressed in Escherichia coli cells in which the cointegrates were prone to deletions although the cad-genes were preserved intact. The latter conclusion is based on the positive reciprocal transfer of the Cad(+)-marker into Yersinia pestis cells. PMID- 1857374 TI - [Use of a multivariate analysis method for determining the interconnection of genetic markers with gene clusters and solution of taxonomy problems for the recombinant influenza A virus model]. AB - The collection of influenza A viral recombinants has been studied for determining interconnection of the definite genetical marker (pneumovirulence for mice) with genes constellation by the technique of image identification. Pneumovirulence is found to be defined by correlation of polymerase complex M-, NS- and NA-genes. The data on NA influence on pneumovirulence were obtained for the first time, the phenomenon being found only with the use of image identification technique. The used methods of image identification (the method of correlation plaiads and cluster analysis) are recommended for use in studying the specificity of the gene control for different genetical features. PMID- 1857375 TI - [Detection of influenza virus nucleoprotein on the surface of infected cells and in free nonvirion form]. AB - The inner viral nucleoprotein synthesized de novo is shown to be exposed on the surface of the chicken embryo infected with influenza virus. The kinetics of the nucleoprotein located on the surface does not correlate with the kinetics of cell destruction. In culture or allantois virus containing liquids the large number of extracellular viral nucleoprotein prone to antinucleoprotein monoclonal antibodies was found. The accumulation of this nucleoprotein occurs in the period when cell destruction is absent, it is eliminated by the adsorption of the virus on erythrocytes or centrifugation at 70,000 g for 2 hours (20%) or by centrifugation at 10,000 g for 4 hours (50%). PMID- 1857376 TI - [Nucleotide sequence of genes and complete amino acid sequence of tick-borne encephalitis virus strain 205]. AB - The 10466 nucleotide long sequence of the cDNA copy of the tick-borne encephalitis strain 205 viral genome has been determined. It includes the 5' nontranslating region, the genes for structural as well as nonstructural proteins and the first 93 nucleotides of 3'-nontranslating region. The difference in amino acid sequences of structural and nonstructural proteins of strains 205. Sofjin and Neudoerfl of the tick-borne encephalitis virus and the nucleotide changes in 5'- and 3'-nontranslating of these strains are discussed. PMID- 1857377 TI - Kinetic properties of fructose bisphosphate aldolase from Trypanosoma brucei compared to aldolase from rabbit muscle and Staphylococcus aureus. AB - The kinetic properties of aldolase from Trypanosoma brucei were studied in comparison with aldolase from rabbit muscle and Staphylococcus aureus. The 3 enzymes displayed a similar broad pH optimum for the cleavage of fructose 1,6 bisphosphate (Fru(1,6)P2) and a similar narrow pH optimum for the cleavage of fructose 1-phosphate (Fru-1-P). However, small alterations in the maximal cleavage rate at more extreme pH values yielded disparities between the pH curves. The reaction catalyzed by the aldolases from T. brucei and S. aureus proceeded via an ordered sequence, as described for the rabbit-muscle enzyme. We determined for the 3 enzymes the kinetic parameters for both the cleavage and the formation of Fru(1,6)P2 and for the cleavage of Fru-1-P. The trypanosomal enzyme differed in its higher ratio of the maximal rate of Fru(1,6)P2-cleavage vs. the maximal rate of Fru(1,6)P2-formation, its higher affinity towards dihydroxyacetone phosphate, and its higher turnover number for the cleavage of Fru-1-P. At ionic strengths above 0.1 M the kinetic parameters of the trypanosomal enzyme followed the limited form of the Debye-Huckel equation. At ionic strengths below 0.1 M the enzyme revealed a characteristic deviation: the apparent Km for Fru(1,6)P2 increased with decreasing salt concentration. The trypanosomal aldolase was competitively inhibited by adenine nucleotides and phosphates. This inhibition occurred in the same concentration range as observed for the rabbit-muscle enzyme, while the bacterial enzyme was less affected. PMID- 1857378 TI - Purification and characterization of a membrane-bound acid phosphatase of Leishmania mexicana. AB - As defined by the reaction with monoclonal antibodies, Leishmania mexicana promastigotes contain two acid phosphatases which together comprise about 90% of the cellular activity. A first enzyme recognized by monoclonal antibody AP4 is largely membrane-bound. The protein has an apparent molecular weight of 70,000 72,000, carries about seven N-linked glycan chains and is present in approximately 16,000 copies per cell. The protein is also expressed in the amastigote stage. A second enzyme reactive with monoclonal antibody AP3, that also recognizes lipophosphoglycan and a secreted acid phosphatase, is mainly found in the soluble fraction of promastigote lysates. It is suggested that this enzyme is the precursor of the secreted protein. The N-terminal sequences of the phosphatase recognized by AP4 and the secreted enzyme are similar but not identical. AP4 does not cross-react with phosphatase activity of Leishmania major or Leishmania donovani promastigotes, while AP3 recognizes part of the cellular and all of the secreted phosphatase activity of L. donovani promastigotes but not that of L. major which does not release an acid phosphatase into the culture medium. PMID- 1857379 TI - Purification and characterization of the 3'-nucleotidase/nuclease from promastigotes of Leishmania donovani. AB - The surface membrane-associated 3'-nucleotidase/nuclease (3'-N'ase) of Leishmania donovani has been purified from detergent extracted promastigotes by anion and cation exchange, lectin affinity and gel filtration chromatography. SDS-PAGE analysis of the purified enzyme preparation revealed a 43-kDa polypeptide as well as faster migrating bands. These bands co-migrated, following both one- and two dimensional electrophoretic analyses, with enzyme activity as determined by an in situ 3'-nucleotidase gel activity assay. It is suggested that the lower molecular weight species arise during purification as a result of proteolytic cleavage of the intact 43-kDa enzyme. The 3'-N'ase exhibited a pI of 5.4, as revealed by 2 dimensional gel electrophoresis. The glycoprotein nature of the 3'-N'ase was suggested by its binding to concanavalin A and by its electrophoretic shift following incubation with N-glycanaseR. In nucleotidase and nuclease assays, the 3'-N'ase was most active with 3'-AMP and poly(A), respectively. Both nucleotidase and nuclease activities exhibited broad pH optima with peaks at 8.5 and 7.5, respectively. At pH 8.5 nucleotidase activity was inhibited by EDTA, Zn2+ and thiols, but was insensitive to tartrate, molybdate and fluoride ions, commonly used inhibitors of phosphatases. The properties of the leishmanial 3'-N'ase was similar to the 3'-N'ase purified from purine-starved Crithidia luciliae, a related trypanosomatid protozoan, and to group of nucleases from fungi and germinating plant seedlings. PMID- 1857380 TI - Chemical modification of fructose bisphosphate aldolase from Trypanosoma brucei compared to aldolase from rabbit muscle and Staphylococcus aureus. AB - Chemical modifications of Class I aldolases from Trypanosoma brucei, rabbit muscle and Staphylococcus aureus with carboxypeptidase A, glyceraldehyde 3 phosphate and cysteine-specific reagents revealed the following differences between the three homologous enzymes. Aldolase from S. aureus was not affected by any of these reagents. Carboxypeptidase-A treatment of rabbit-muscle and T. brucei aldolase inhibited the activity of both enzymes towards fructose-1,6 bisphosphate (Fru(1,6)P2), while the activity towards fructose-1-phosphate (Fru-1 P) was affected only in the case of the trypanosomal enzyme. Moreover carboxypeptidase-A treatment reduced the turnover numbers of these two aldolases for both Fru(1,6)P2 and Fru-1-P to a similar level. Glyceraldehyde 3-phosphate, in the absence of dihydroxyacetone phosphate, also inactivated aldolases from rabbit muscle and T. brucei with second order rate constants of 1054 and 254 min 1 M-1, respectively. Using 5,5'-dithiobis-(2-nitrobenzoic acid) with rabbit muscle aldolase, a total of 4 thiol groups could be titrated per subunit, resulting in a total inactivation. The presence of substrate completely protected the enzyme from inactivation. Methyl methanethiosulfonate also reacted with four cysteine residues, but this led to very little inactivation. This indicates that the inactivation by modification with DTNB is due to conformational changes in the enzyme. In T. brucei aldolase only one thiol group could be titrated with methyl methanesulfonate and there was no loss of activity. With 5,5'-dithiobis-(2 nitrobenzoic acid) five cysteines were titrated with an immediate and complete loss of activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1857381 TI - Characterization of a novel developmentally regulated gene from Trypanosoma brucei encoding a potential phosphoprotein. AB - We have isolated a cDNA clone corresponding to a single-copy nuclear gene that is upregulated at the mRNA level during in vitro differentiation of bloodstream trypomastigotes of strains of both Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense to procyclic forms. Transcript levels begin to increase within minutes of introduction of bloodstream forms into culture and peak well before cultures exhibit a procyclic morphology. This increase in transcript levels was found to occur both in the absence of protein synthesis and in a nontransforming strain blocked very early in the developmental program, both conditions under which accumulation of procyclic acidic repetitive protein (PARP) transcripts did not occur in control experiments. DNA sequence analysis reveals an open reading frame sufficient to encode a protein of approximately 50 kDa within the cDNA, but data base searches for homology at either the amino acid or nucleotide level revealed no related sequences. A high density of kinase consensus target sites in the deduced amino acid sequence suggests that the gene product may be a phosphoprotein. PMID- 1857383 TI - Characterization of pyruvate kinase of Trypanosoma brucei and its role in the regulation of carbohydrate metabolism. AB - Pyruvate kinase from Trypanosoma brucei is a labile enzyme, losing its activity within several hours. In mixtures containing 50 mM triethanolamine buffer, pH 7.2, 25% glycerol and 0.5 mM inorganic phosphate the enzyme remained active and could be purified to homogeneity with a specific activity of 417 units mg-1 and a yield of 65%. The enzyme has an activation energy of 31.9 kJ mol-1. Magnesium and potassium ions are essential for activity. Cobalt or manganese ions replace Mg2+ but this leads to a decrease in maximal velocity. Potassium ions can be substituted by ammonium ions, while sodium ions behave as a competitive inhibitor with respect to both K+ and NH4+. All metal ions studied displayed sigmoidal kinetics. The enzyme is activated, with decreasing efficiency by fructose 2 phosphorothioate 6-phosphate, fructose 2,6-bisphosphate, fructose 1,6 bisphosphate and glucose 1,6-bisphosphate. They all display hyperbolic kinetics. Glycerate 2,3-bisphosphate, glyceraldehyde 3-phosphate, CoASAc, oxalate, AMP, ADP, and ATP inhibit the enzyme. At substrate saturation PK was activated by Pi up to a concentration of 0.8 mM. At higher Pi concentrations the enzyme is inhibited. The enzyme is unaffected by most amino acids, only phenylalanine stimulates and tyrosine inhibits. PMID- 1857382 TI - Beta-tubulin and benzimidazole resistance in the sheep nematode Haemonchus contortus. AB - We have compared benzimidazole (BZ) susceptible (s) and resistant (R) strains of Haemonchus contortus from sheep by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), Western blotting and ELISA techniques. The S strain bound more drug per mg protein than the R strain. BZ binding could be resolved into high-affinity and low-affinity binding. Low-affinity binding in parasite preparations devoid of tubulin was observed, but high-affinity binding occurred only in preparations containing tubulin. Resistance was associated with a decrease in the high affinity component. The S and R strains were shown by ELISA to contain similar total amounts of tubulin. By 2-D PAGE, the beta-tubulin isoform pattern of the S strain was different from that of the R strain, but the alpha-tubulin isoform patterns of the 2 strains were similar. BZ resistance was associated with a decrease in high-affinity BZ binding to tubulin and an alteration in beta-tubulin isoform pattern. PMID- 1857384 TI - Inhibition of the growth of Plasmodium falciparum and Plasmodium berghei by the DNA polymerase inhibitor HPMPA. AB - The acyclic adenosine analogue (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [HPMPA] belongs to a class of nucleoside analogues originally described as having potent activity against a broad spectrum of DNA viruses. We examined the effects of this class of drugs on the growth of cultured Plasmodium falciparum. Strong inhibition was observed by HPMPA (ID50 = 47 nM) at concentrations more than 1000 fold less than the cytotoxic dose for human cells. 3-deaza-HPMPA was even more strongly inhibitory (ID50 = 8 nM), whereas several other acyclic nucleosides were not effective. In mice infected with Plasmodium berghei, increase of parasitaemia can be blocked for 4-6 days by a single injection of HPMPA. Repeated drug administration blocks parasite growth for prolonged periods at doses that are clinically feasible. We also determined the inhibition of several purified Plasmodium DNA polymerases by diphosphorylated HPMPA (HPMPApp). DNA polymerase alpha-like enzymes of P. falciparum and P. berghei are inhibited with an IC50 = 40 microM and a gamma-like DNA polymerase from P. falciparum is even 40-fold more sensitive to the drug. The inhibition by HPMPApp is competitive with dATP, strongly suggesting that Plasmodium DNA polymerases are targets for this class of nucleotide analogue. PMID- 1857385 TI - Isolation and characterization of rhoptries of Plasmodium falciparum. AB - Rhoptries have been isolated from Plasmodium falciparum schizont-infected erythrocytes by isopycnic density centrifugation. Gradient fractions were analyzed by immunoblotting with antibodies against two polypeptides of 140 and 110 kDa, known to be components of the rhoptry. The proteins were present primarily in fractions with a density of 1.16 g ml-1. Electron microscopy of these fractions indicated they were enriched in rhoptries. For the most part, the isolated organelle retained in situ morphology, although some rhoptries were distorted, indicating the structure of some of the organelles is not rigid. Electrophoretic analysis of the rhoptry fractions indicated the presence of a number of proteins, many of which have not been identified to date. Properties of proteins in the isolated rhoptry were examined using the 140 and 110 kDa proteins as representative markers. Both proteins are present in a complex with a 130-kDa protein, as all three co-immunoprecipitate. At the late schizont stage, the rhoptry proteins are present in two distinct forms; a soluble form with an Mr of 480 000 which would correspond to a single copy of the 140/130/110 kDa complex and a form that can be sedimented at 130 000 x g. Properties of the sedimentable form suggest that the proteins are included in structures that resemble membranes. Ionic detergents were required to solubilize the proteins while high concentrations of NaCl and Na2CO3 resulted in only partial solubilization. Furthermore, treatment of disrupted rhoptries with phospholipase A and C resulted in the release of proteins into the soluble form. PMID- 1857387 TI - Differences in glucose transport between blood stream and procyclic forms of Trypanosoma brucei rhodesiense. AB - In African trypanosomes the requirements for glucose and its metabolism vary in different stages of the life cycle. Here we present evidence that cultured procyclic trypanosomes of Trypanosoma brucei rhodesiense uptake glucose against a concentration gradient in a time and dose-dependent manner. Moreover, glucose transport is completely inhibited by the sulphydryl inhibitor N-ethylmaleimide, suggesting the presence of a protein moiety as the carrier molecule. Comparison of glucose uptake in bloodstream and procyclic trypanosomes point to the possibility that different transporters may function in the 2 developmental stages. Glucose uptake by bloodstream trypanosomes requires Na+ ions and is inhibited by phlorizin, an inhibitor of Na(+)-dependent glucose transporters in mammalian cells. Conversely, procyclic trypanosomes transport glucose in a Na(+) dependent manner, and transport is not affected by phlorizin. Finally, the putative procyclic glucose transporter has a higher affinity for glucose (apparent Km 23 microM) than the bloodstream carrier (apparent Km 237 microM). PMID- 1857386 TI - A recombinant clone of Wuchereria bancrofti with DNA specificity for human lymphatic filarial parasites. AB - In order to understand the immune response to Wuchereria bancrofti and to aid in the diagnosis of W. bancrofti infections, recombinant antigens were identified from a W. bancrofti genomic expression library made in lambda gt11 using a pool of sera from infected Indian patients. One of the recombinant clones, lambda WbN1, containing a 2.5-kb insert, reacted strongly to a pool of sera from patients with lymphatic filariasis but not to normal human sera. In addition, this clone showed restricted specificity at the genomic level to the major lymphatic filarial parasites W. bancrofti and Brugia malayi but not to the closely related filarial parasite Brugia pahangi or to other filarial and non filarial species tested. Nucleotide sequence analysis indicated the cloned DNA to have homology to myosin-like myofibrillar proteins. Polymerase chain reaction amplification initiated by specific synthetic oligomers amplified DNA in a species-specific manner from as little as 16 pg of isolated DNA or from one microfilaria. PMID- 1857388 TI - Substrate-dependent pH optima of gp63 purified from seven strains of Leishmania. AB - The major surface glycoprotein of Leishmania, gp63, is a membrane-bound metalloprotease. Contradictory data supporting a neutral or acidic nature of this enzyme have been presented. Seven strains of Old and New World Leishmania, including Leishmania donovani complex (Leishmania infantum and L. donovani), Leishmania major, Leishmania tropica and Leishmania mexicana amazonensis were used for the purification and comparative study of gp63. The protein was extracted from promastigotes by phase separation in Triton X-114 and purified by anion exchange chromatography. In agreement with previous reports, all purified gp63 were found to be structurally and immunologically related. Both membrane bound gp63, on the surface of promastigotes, and the purified proteases had optimal activity at neutral to alkaline pH on azocasein, whereas their activity was optimal at acidic to neutral pH against 125I-insulin B-chain. The IC50 concentrations of 1,10-phenathroline against the two substrates, at the optimal pH, were comparable, suggesting that both activities measured were associated with gp63 rather than another contaminating enzyme. This was further supported by the comparable enrichment values, estimated from the specific activity of the enzyme during purification, using both assays. These results explain the earlier apparent discrepancies and suggest that the optimum pH of gp63 is substrate dependent and not related to species differences or to the different purification procedures applied. PMID- 1857389 TI - Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis. AB - BACKGROUND: Cystic fibrosis is characterized by abnormal electrolyte transport across the epithelia of the airways. In particular, there is excessive sodium absorption and deficient chloride secretion. Drugs that block excessive sodium absorption may provide clinical benefit in cystic fibrosis, but there are no available therapeutic agents to improve chloride secretion. In vitro studies in cultured human-airway epithelia indicate that triphosphate nucleotides (ATP and UTP) induce chloride secretion through apical-membrane purinergic receptors. METHODS: We tested the ability of nucleotides to induce chloride secretion in vivo in 9 normal subjects and 12 patients with cystic fibrosis by measuring responses of nasal transepithelial potential difference (PD) to superfusion of nucleotides. Changes in transepithelial bioelectric properties and the permeability of the apical membrane to chloride in response to extracellular (apical) UTP were determined with ion-selective microelectrodes in cultured nasal epithelia. RESULTS: ATP and UTP induced chloride secretion in vivo in both groups. At their maximal effective concentrations of 10(-4) M, ATP and UTP were more effective chloride secretagogues in the patients with cystic fibrosis (mean [+/- SE] change in PD, -19.8 +/- 1.4 mV and -15.0 +/- 1.7 mV, respectively) than in the normal subjects (-6.9 +/- 0.6 mV and -8.1 +/- 0.9 mV, respectively). Microelectrode studies established that extracellular UTP stimulated a larger increase in PD and chloride secretory current in epithelial cells from patients with cystic fibrosis than in cells from normal subjects, by actions localized to the apical membrane. CONCLUSIONS: Extracellular nucleotides are effective in vivo chloride secretagogues in the nasal epithelia of patients with cystic fibrosis. The equipotency of ATP and UTP suggests that the effect is mediated by P2 nucleotide receptors. Selected nucleotides, such as UTP or nucleotide analogues, should be investigated as therapeutic agents for lung disease in cystic fibrosis. PMID- 1857390 TI - Rapid loss of vertebral mineral density after renal transplantation. AB - BACKGROUND: Osteopenia is a major complication of renal transplantation. Immunosuppressive regimens including cyclosporine, which permit the use of lower doses of glucocorticoids, may reduce glucocorticoid-induced osteopenia. METHODS: We prospectively studied the magnitude, distribution, and mechanism of bone loss in 20 adults who received renal allografts from living related donors, who had good renal function, and who were treated with azathioprine, cyclosporine, and low doses of prednisone. We measured serum biochemical markers of bone metabolism, determined the bone mineral density of the second, third, and fourth lumbar vertebrae and the shaft of the radius, and analyzed the histomorphometric features of iliac bone at the time of transplantation and six months later. Measurements of vertebral mineral density were repeated 18 months after transplantation in 17 of the patients. RESULTS: After transplantation, the mean serum concentrations of parathyroid hormone, phosphorus, and alkaline phosphatase decreased and the serum calcitriol concentration increased. The mean (+/- SD) bone mineral density of the vertebrae had decreased 6.8 +/- 5.6 percent 6 months after transplantation (P less than 0.05) and 8.8 +/- 7.0 percent 18 months after transplantation. In contrast, the bone mineral density of the radius had increased six months after transplantation (P less than 0.05). The histomorphometric studies showed that the rate of bone formation decreased from 50.5 +/- 44.8 to 23.1 +/- 13.8 microns3 per square micrometer per year (P less than 0.05), and the formation period lengthened from 70 +/- 42 to 146 +/- 144 days (P less than 0.05). Consequently, the amount of bone replaced during a remodeling cycle diminished. CONCLUSIONS: Osteopenia associated with renal transplantation remains a problem in the cyclosporine era. The loss of vertebral bone in our subjects was due to an imbalance in bone remodeling consistent with a toxic effect of glucocorticoids. PMID- 1857392 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 34-1991. A 51-year-old man with severe hypertension and rapidly progressive renal failure. PMID- 1857393 TI - Untoward effects of gas masks during Persian Gulf war. PMID- 1857391 TI - The use of angioplasty, bypass surgery, and amputation in the management of peripheral vascular disease. AB - BACKGROUND: Percutaneous transluminal angioplasty has been adopted widely as a treatment for patients with peripheral vascular disease of the lower extremities. However, the effect of this procedure on the overall management of peripheral vascular disease and on the outcomes of patients has not been clearly delineated. In particular, it is not known whether angioplasty has replaced other treatments for peripheral vascular disease. METHODS: To assess the extent to which angioplasty is used and the associated changes in the surgical management of peripheral vascular disease of the lower extremities, we used data on hospital discharges in Maryland to identify all angioplasty procedures, peripheral bypass operations, and lower-extremity amputations performed for peripheral vascular disease in Maryland hospitals between 1979 and 1989. RESULTS: We estimated that from 1979 to 1989 the annual rate of percutaneous transluminal angioplasty for peripheral vascular disease of the lower extremities, adjusted for age and sex, rose from 1 to 24 per 100,000 Maryland residents (P less than 0.0001 by linear regression). Despite this increase in the use of angioplasty, the adjusted annual rate of peripheral bypass surgery also rose substantially, from 32 to 65 per 100,000 (P less than 0.001), whereas the adjusted annual rate of lower-extremity amputation remained stable at about 30 per 100,000. Total charges for hospitalizations during which a peripheral revascularization procedure was performed increased from $14.7 million in 1979 (in 1989 dollars) to $30.5 million in 1989. CONCLUSIONS: In Maryland, the adoption of percutaneous transluminal angioplasty for peripheral vascular disease of the lower extremities has been associated with an increase in the use of peripheral bypass surgery and with no decline in lower-extremity amputations. These results could be due to increased diagnosis of peripheral vascular disease, expanded indications for procedural interventions, or an increased number of repeat procedures performed in patients with peripheral vascular disease of the lower extremities. PMID- 1857394 TI - Normal plasma cholesterol in a man who eats 25 eggs a day. PMID- 1857395 TI - Prednisone in the prevention of early relapse after treatment of acute asthma. PMID- 1857396 TI - Evidence of free-radical activity in asthma. PMID- 1857397 TI - Confusion about drug names. PMID- 1857398 TI - Rhinosporidium seeberi: light, phase contrast, fluorescent and scanning electron microscopic study. AB - Phase contrast microscopic study indicated the multilayered structure of the sporangial wall of R. seeberi while the scanning electronmicroscopic study revealed a trilaminated wall compared to a thick double walled light microscopic structure. The scanning electronmicroscopy revealed the spores of varying sizes which were found either discretely or in groups interconnected and seen attached to the inner aspect of the sporangial wall. Autofluorescence of sporangia and spores was observed under microscope. Acridine orange staining revealed the presence of DNA materials in the spore and sporangia. PMID- 1857399 TI - Aspergillus clavatus as the probable cause of a lethal mass neurotoxicosis in sheep. AB - Sprouted barley grains, the waste product of malt extract production, were incriminated as the cause of a lethal (96% mortality) neurotoxic syndrome in sheep fed the grains. Clinical manifestations, comprising tremors, lameness, abnormal gait, paralysis and death indicated a tremorgenic mycotoxicosis. Whilst 50% of the flock died within 17 days, mortality continued over more than 5 months. Pathological findings were limited to neuronal degeneration and necrosis in the midbrain. Germinating grains were shown to be contaminated with growth of Aspergillus clavatus. PMID- 1857400 TI - Scanning electron microscopy of the conidia produced by the mycelial form of Paracoccidioides brasiliensis. AB - The conidia produced by the mycelial form of Paracoccidioides brasiliensis were examined by scanning electron microscopy for the first time. Several different conidial types were characterized. These included intercalary arthroconidia, several types of septate conidia that are formed from other conidia, pedunculate conidia, and terminal hyphal conidia. In addition, the ultrastructure of the supporting pedestal of the pedunculate conidium was found to be separated from the mother conidium by a septum in some instances, and at other times it was not. PMID- 1857401 TI - German science. DFG selects new president. PMID- 1857402 TI - Boost for women's health. PMID- 1857403 TI - Genome researchers go hog wild. PMID- 1857404 TI - Zagury challenges NIH report. PMID- 1857405 TI - Responsibility and Weaver et al. PMID- 1857406 TI - Dissent on forensic evidence. PMID- 1857407 TI - Detection of human carcinogens. PMID- 1857408 TI - Retinoblastoma. A transcriptional tryst. PMID- 1857409 TI - Evolution. Matriarchal liberation. PMID- 1857410 TI - Developmental biology. A marriage is consummated. PMID- 1857411 TI - Anti-HIV drug mechanism. PMID- 1857412 TI - Risks to VDT operators. PMID- 1857413 TI - Stimulation by superantigen. PMID- 1857414 TI - Spontaneous mutation rate. PMID- 1857415 TI - Object awareness. PMID- 1857416 TI - Interaction of bride of sevenless membrane-bound ligand and the sevenless tyrosine-kinase receptor. AB - During development of the Drosophila retina, the R8 photoreceptor neuron induces a neighbouring cell to assume an R7 cell fate. Genetic data suggest that the induction is mediated by two transmembrane proteins encoded by bride of sevenless and sevenless. A direct interaction between these two proteins was demonstrated by the heterotypic aggregation of cell lines expressing them. In the developing eye the sevenless-dependent internalization of bride of sevenless by the R7 precursor cell provides evidence for a direct interaction between these two proteins in vivo. PMID- 1857417 TI - Structural basis of anticodon loop recognition by glutaminyl-tRNA synthetase. AB - The refined crystal structure of Escherichia coli glutaminyl transfer RNA synthetase complexed with transfer RNA(Gln) and ATP reveals that the structure of the anticodon loop of the enzyme-bound tRNA(Gln) differs extensively from that of the known crystal structures of uncomplexed tRNA molecules. The anticodon stem is extended by two non-Watson-Crick base pairs, leaving the three anti-codon bases unpaired and splayed out to bind snugly into three separate complementary pockets in the protein. These interactions suggest that the entire anticodon loop provides essential sites for glutaminyl tRNA synthetase discrimination among tRNA molecules. PMID- 1857418 TI - Better speech recognition with cochlear implants. AB - HIGH levels of speech recognition have been achieved with a new sound processing strategy for multielectrode cochlear implants. A cochlear implant system consists of one or more implanted electrodes for direct electrical activation of the auditory nerve, an external speech processor that transforms a microphone input into stimuli for each electrode, and a transcutaneous (rf-link) or percutaneous (direct) connection between the processor and the electrodes. We report here the comparison of the new strategy and a standard clinical processor. The standard compressed analogue (CA) processor presented analogue waveforms simultaneously to all electrodes, whereas the new continuous interleaved sampling (CIS) strategy presented brief pulses to each electrode in a nonoverlapping sequence. Seven experienced implant users, selected for their excellent performance with the CA processor, participated as subjects. The new strategy produced large improvements in the scores of speech reception tests for all subjects. These results have important implications for the treatment of deafness and for minimal representations of speech at the auditory periphery. PMID- 1857419 TI - Spontaneous calcium release from inositol trisphosphate-sensitive calcium stores. AB - Inositol 1,4,5-trisphosphate (InsP3) functions as a second messenger to mobilize Ca2+ from intracellular reservoirs. The release mechanism displays all-or-none characteristics, that may account for other observations that the InsP3-induced mobilization of Ca2+ is quantal. Quantal release may depend on the sensitivity of the InsP3 receptor being regulated by the Ca2+ concentration in the lumen of the endoplasmic reticulum. We report here that the InsP3-sensitive store in hepatocytes discharges spontaneously when overloaded with Ca2+. The release, which is blocked by heparin, is preceded by an increasing sensitivity of the InsP3 receptor to endogenous InsP3, and is promoted by those sulphydryl reagents (oxidized glutathione and thimerosal) that induce Ca2+ oscillations in intact cells (ref. 8, and T. A. Rooney, D. C. Renard, E. J. Sass and A. P. Thomas, manuscript in preparation). This novel process could have a role in generating both Ca2+ oscillations and Ca2+ waves. PMID- 1857420 TI - ATP-sensitive K+ channel in the mitochondrial inner membrane. AB - Mitochondria take up and extrude various inorganic and organic ions, as well as larger substances such as proteins. The technique of patch clamping should provide real-time information on such transport and on energy transduction in oxidative phosphorylation. It has been applied to detect microscopic currents from mitochondrial membranes and conductances of ion channels in the 5-1,000 pS range in the outer and inner membranes. These pores are not, however, selective for particular ions. Here we use fused giant mitoplasts prepared from rat liver mitochondria to identify a small conductance channel highly selective for K+ in the inner mitochondrial membrane. This channel can be reversibly inactivated by ATP applied to the matrix side under inside-out patch configuration; it is also inhibited by 4-aminopyridine and by glybenclamide. The slope conductance of the unitary currents measured at negative membrane potentials was 9.7 +/- 1.0 pS (mean +/- s.d., n = 6) when the pipette solution contained 100 mM K+ and the bathing solution 33.3 mM K+. Our results indicate that mitochondria depolarize by generating a K+ conductance when ATP in the matrix is deficient. PMID- 1857421 TI - Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product. AB - The E7 transforming protein of human papilloma virus-16 binds to the retinoblastoma gene product (pRb) through a nine-amino-acid segment of E7 (21 29). This segment of E7 is homologous to the pRb-binding domains of the simian virus 40 large T and adenovirus E1A transforming proteins. Each of these viral transforming proteins bind to the same region of pRb. To isolate cellular proteins that interact with this viral protein-binding domain on pRb, we used recombinant pRb to screen a human complementary DNA expression library. Two cDNAs were isolated that encode retinoblastoma binding proteins (RBP-1 and RBP-2). We report here that these RBP genes exist in separate loci and produce discrete messenger RNAs. The predicted amino-acid sequence of these genes showed no homology to known proteins, but both RBPs contain the pRb binding motif conserved between E7, large T and E1A14. In vitro expression of the RBP cDNAs yielded proteins that specifically bound to pRb. Recombinant E7 protein, the E7 21-29 peptide and the homologous RBP-1 peptide inhibited RBP-pRb binding. Mutations introduced into the putative pRb-binding segment in RBP-1 impaired its binding activity. These studies indicate that the cellular RBP-1, RBP-2 and viral E7 proteins interact with pRb through similar domains. PMID- 1857422 TI - Paternal inheritance of mitochondrial DNA in mice. AB - For nearly 20 years it has been assumed on the basis of low-resolution experiments that mitochondrial (mt)DNA, in contrast to the genes in the nucleus, has an exclusively maternal mode of inheritance in animals. Using the polymerase chain reaction, paternally inherited mtDNA molecules have now been detected in mice at a frequency of 10(-4), relative to the maternal contributions. These mice were hybrids between two inbred strains (C57BL/6J and Mus spretus) whose mtDNAs can be distinguished easily. This new mode of inheritance provides a mechanism for generating heteroplasmy and may explain mitochondrial disorders exhibiting biparental transmission. PMID- 1857423 TI - Anticodon and acceptor stem nucleotides in tRNA(Gln) are major recognition elements for E. coli glutaminyl-tRNA synthetase. AB - The correct attachment of amino acids to their corresponding (cognate) transfer RNA catalysed by aminoacyl-tRNA synthetases is a key factor in ensuring the fidelity of protein biosynthesis. Previous studies have demonstrated that the interaction of Escherichia coli tRNA(Gln) with glutaminyl-tRNA synthetase (GlnRS) provides an excellent system to study this highly specific recognition process, also referred to as 'tRNA identity'. Accurate acylation of tRNA depends mainly on two principles: a set of nucleotides in the tRNA molecule (identity elements) responsible for proper discrimination by aminoacyl-tRNA synthetases and competition between different synthetases for tRNAs. Elements of glutamine identity are located in the anticodon and in the acceptor stem region, including the discriminator base. We report here the production of more than 20 tRNA(2Gln) mutants at positions likely to be involved in tRNA discrimination by the enzyme. Unmodified tRNA, containing the wild-type anticodon and U or G at its 5' terminus, can be aminocylated by GlnRS with similar kinetic parameters to native tRNA(2Gln). By in vitro aminoacylation the mutant tRNAs showed decreases of up to 3 x 10(5)-fold in the specificity constant (kcat/KM)14 with the major contribution of kcat. Despite these large changes, some of these mutant tRNAs are efficient amber suppressors in vivo. Our results show that strong elements for glutamine identity reside in the anticodon region and in positions 2 and 3 of the acceptor stem, and that the contribution of different identity elements to the overall discrimination varies significantly. We discuss our data in the light of the crystal structure of the GlnRS:tRNA(Gln) complex. PMID- 1857424 TI - Radioactive cell membrane labelling. AB - Building upon earlier studies with fluorescent probes, the authors describe a new cell tracking compound, PKH95, with a radioactive signal, which has been developed specifically for high-sensitivity cell tracking and biodistribution studies. PMID- 1857425 TI - Thirty-seven-year follow-up of an infant born with severe renal tubular acidosis. A tribute to the care and training of Bailey Webb, Ph.D., M.D. PMID- 1857426 TI - The Duke University Arthritis Center. AB - The Duke University Arthritis Center has brought together both clinicians and basic scientists into a common structure to achieve a singular goal--that of improving the health and welfare of patients with immune-mediated diseases in North Carolina and surrounding states. The structure of DUAC allows new insights gained by basic immunologic research to be rapidly applied to clinical rheumatologic diseases by channelling basic information to the clinical investigative unit in DUAC. Here new treatment strategies are developed and tested and made available to patients when they are judged to be both safe and efficacious. In the DUAC comprehensive clinics, the best treatments available to patients with rheumatologic diseases are provided in a setting designed to be user-friendly to patients and comprehensive in services offered. PMID- 1857427 TI - The University of North Carolina Arthritis Center. AB - The University of North Carolina Arthritis Center combines the broadly-based research agenda of the Thurston Arthritis Research Center with comprehensive interdisciplinary clinical programs in rheumatology, orthopaedics, and pediatric rheumatology. In keeping with the University's long tradition of service to the people of North Carolina, a primary aim of the Center is to provide the citizens of this state with the best available arthritis care and prevention strategies. The approach here is twofold. New knowledge is created by laboratory investigation of basic disease mechanisms, by clinical studies of new therapies, by social and behavioral research to better understand how patients and their families cope and adjust to chronic arthritis, and by health services research that examines arthritis from a societal perspective. This information, together with advances in rheumatology and related fields from Duke and other institutions, is then applied to optimum clinical and educational services for North Carolina patients and their physicians. PMID- 1857428 TI - Which one is Hardy? Ibuprofen overdose. PMID- 1857429 TI - Adolescent childbearing. PMID- 1857430 TI - Adolescent health issues: what is our role? PMID- 1857431 TI - The North Carolina Medical Society--medical student section. Medical students getting involved. PMID- 1857432 TI - Resource-Based Relative Value Scale. PMID- 1857433 TI - Comment on Dr. Edell's article on the high tech newborn. PMID- 1857434 TI - [Intermaxillary fixation in traumatology]. PMID- 1857435 TI - [A reputed leptospirosis epidemic as a consequence of swimming in the Spokeplas]. PMID- 1857436 TI - [Exogenous modification of reproductive disorders; more questions than facts]. PMID- 1857437 TI - [Pulmonary hypertension and cor pulmonale caused by chronic obstructive lung disease; pathogenesis and treatment]. PMID- 1857438 TI - [Good results with the surgical treatment of trigger finger (tendovaginitis stenosans)]. AB - Stenosing tendovaginitis (trigger finger) may be treated surgically or conservatively. Surgical incision of the proximal part of the flexor tendon sheath in 100 patients (91 adults and 9 children) proved a reliable method. In 97 patients the resistance was abolished by surgical treatment, with good functional results. It is a simple procedure, with hardly any complications and a short follow-up period. PMID- 1857439 TI - [Tuberculosis in alpacas; a zoonosis as an imported disease]. AB - In the Netherlands, in 1988, a micro-epidemic of tuberculosis in alpacas recently imported from Peru prompted health authorities to initiate investigation of human and animal contacts. Although the animal trainer and his assistant suffered from pulmonary tuberculosis, they turned out to be infected by Mycobacterium tuberculosis, while the animals later proved to be infected by M. bovis. The alpacas' caretaker and a laboratory technician present at the autopsy, were probably infected by animal contact. Elsewhere in the country, three more alpacas were reported with tuberculosis at the time; this initiated a large-scale investigation among alpacas, llamas etc., but no further cases were detected. The possibility of imported zoonoses, especially after 1992, is discussed. PMID- 1857440 TI - [Postoperative irradiation in grade III and IV astrocytoma]. AB - The aim of this paper is to contribute to the discussion on the value of postoperative radiotherapy in patients with astrocytoma grade III-IV. One hundred and fifteen of the 243 patients with histologically proven astrocytoma grade III IV received postoperative radiotherapy at the St. Radboud University Hospital Nijmegen. According to the protocol all patients with a fairly good performance status were irradiated. The extent of surgery consisted of biopsy alone in 11%, subtotal tumour resection in 85% and macroscopically complete tumour removal in 4%. All patients received a whole brain irradiation of 40 Gy with a boost of 10 15 Gy in the tumour. Patients with grade III who underwent surgical resection had a median survival of 2.1 months, those with grade IV 2.7 months. Patients who underwent surgical resection and radiotherapy had a median survival of 12 months (grade III) and 8.6 months (grade IV). The extent of surgery and grade of malignancy were the only prognostic factors. Because of the selection of patients this study produces no additional arguments in favour of postoperative radiotherapy. However, we continue our treatment strategy to irradiate patients with grade III-IV tumours because the median survival obtained with this strategy is high in comparison with data from literature. PMID- 1857441 TI - [Toxic damage of kidney, liver and muscle attributed to the administration of germanium-lactate-citrate]. AB - The case history is described of a woman aged 57 years with renal, hepatic and muscular damage attributed to intake of germanium lactate-citrate (a cumulative dose of 32.1 g germanium) over at least one year, as alternative treatment of metastatic breast cancer. Histological examination of biopsies showed highly vacuolated cytoplasm of the epithelial cells of the distal renal tubules and micro- and macrovesicular steatosis of centrilobular hepatocytes. After discontinuation of the germanium, serum aminotransferases and creatine kinase values returned to normal, but moderately severe renal impairment persisted. PMID- 1857442 TI - [How bad was Chernobyl? Psychosocial sequelae of the reactor accident]. PMID- 1857443 TI - [Ectopic ureter outlet in women; easy to overlook]. PMID- 1857444 TI - [No increase in the incidence of breast carcinoma with subcutaneous administration of estradiol]. PMID- 1857446 TI - [Orthomanual medicine]. PMID- 1857445 TI - [Smoke about leg cramps]. PMID- 1857447 TI - Changes in the toxicity and therapeutic efficacy of daunorubicin linked with a biodegradable carrier. AB - The effects of the linkage of daunorubicin (DNR) and the synthetic biodegradable polymer polyhydroxyethyl-L-glutamine (PHEG) on general toxicity, therapeutic efficacy, and acute organ toxicity were investigated. General toxicity was assessed by means of mortality, or body weight changes of male CBA mice weighing 22-25 g after a single-dose i.p. administration of 5 or 2.5 mg/kg DNR, free or bound. Linked DNR at a larger lethal dose significantly increased mean survival time (18 versus 12 days). Surprisingly, free DNR at a smaller dose produced larger increases in body weight as compared with linked DNR. The linkage of DNR and PHEG did not markedly change the therapeutic activity in three murine hemoblastoses--plasmacytoma MOPS 406, leukemia P388 and hemoblastosis La. Acute (24 h) changes in cardio- and hepatotoxicity were studied on female Wistar rats weighing 208 +/- 5 g after a single dose of 5 mg/kg i.v. both free and linked DNR, as well as after an administration of the PHEG polymer alone (200 mg/kg i.v.). Free DNR caused a three-fold increase in creatine kinase (CK) activity, the identical dose of linked DNR caused only a 1.7-fold increase. Free DNR administration resulted in a decrease in heart rate, other tested drugs did not significantly change either blood pressure or heart rate. Free DNR did not change the kinetics of bromsulphalein (BSP) except for a decrease in extraction effectivity. Both linked DNR and polymer alone significantly changed some kinetic parameters of BSP. The results showed that the biodegradable polymer PHEG cannot be clinically used due to its hepatotoxic action. On the other hand, a decrease in total toxicity and cardiotoxicity resulting from the linkage of DNR and PHEG, the therapeutic efficacy being preserved, stimulates the efforts to find a suitable polymer carrier of anthracyclines without more serious side-effects. PMID- 1857448 TI - Subrenal capsule assay of human tumor chemosensitivity. AB - Breast and colon tumor response to emoxyl, a nitroxyl derivative of daunomycin, was detected using human tumor heterotransplantation under the renal capsule of immunocompetent mice. The substitution of adriamycin by emoxyl in the combined therapy led to enhanced therapeutic efficacy. The evidence of enhanced response of breast tumors to emoxyl obtained during the histologic examination of xenografts is in good agreement with measurements of tumor fragment weight. It is suggested to use a quantitative kinetic index kappa calculated by the method of equivalent exponents for objective evaluation of tumor response to the drugs. PMID- 1857449 TI - Some electrochemical characteristics of synthetic analogs of nucleic acid components. IV. 5-Cyano-, 5-carboxy- and 5-azaderivatives, and the effect of this substitution on potential carcinogenicity. AB - The relation between polarographic reduction, values of half-wave potentials, and the parameter of potential carcinogenicity (tg alpha) was studied in a series of synthetic analogs of natural nucleic acid components modified by different substituents at position 5 of the base. The series included pyrimidine nucleobases (5-cyanouracil, 5-carboxycytosine, 5-azacytosine), ribofuranosyl nucleosides (5-cyanouridine, 5-carboxycytidine, 5-azacytidine) as well as 2' deoxy-5-azacytidine and 5-carboxy-1-beta-D-arabinosylcytosine. No direct correlation was found between the reducibility of the studied compounds and the parameter of potential carcinogenicity tg alpha since event a slight alteration in the structure of these molecules markedly affected the properties of these compounds. PMID- 1857450 TI - NK-cell activity affected by some cytostatic drugs and their additives. AB - The direct effect of selected cytostatic drugs on natural killer (NK) cell activity was evaluated. Peripheral blood mononuclear cells from healthy donors were tested for their cytolytic activity in vitro in the presence of adriamycin, methotrexate, leucovorin, vincristin, cytosine arabinoside and teniposide. Most of the tested cytostatic drugs did not show to be active at concentrations comparable to their plasma level. However, diluents of some preparations (cytosine arabinoside, teniposide) containing organic solutions and stabilizing additives (e.g. benzyl alcohol) suppressed the NK activity more than chemotherapeutic agents alone. Thus teniposide, containing such additives, inhibited NK activity already at 5 mg/ml, while its peak plasma concentration was 23.8 mg/ml. The inhibitory concentrations of teniposide did not affect the target binding of effector cells and the expression of 14 tested leukocyte differentiation markers. This implies that a postbinding step of the lytic process was altered by the preparation. Likewise, no inhibition of lectin dependent cellular cytotoxicity by teniposide and its diluent was observed, suggesting that the lectin may substitute the missing lytic signal. PMID- 1857451 TI - The role of humoral factors of regenerating liver in the development of experimental tumors and the effect of Rhodiola rosea extract on this process. AB - In experiment on rats with Pliss lymphosarcoma (PLS) it was shown that partial hepatectomy (PHE), a course application of Rhodiola rosea extract (RRE) or combined effects inhibit the growth of tumors by 37, 39 and 59%, respectively, and that of metastases by 42, 50 and 75%. In combined treatment the process of hepatic regeneration was completed in earlier terms versus the animals which underwent PHE, and proliferative activity of the tumor and metastases decreased by 15 and 59%, respectively, judging by the degree of 3H-thymidine incorporation into DNA of these tissues. The assessment of clonogenic activity of PLS cells taken in the animals of this group, using the method of diffusion chambers, revealed a significant decrease in this index versus the rats which underwent PHE or which were given RRE (number of colonies per chamber being 4.8 +/- 0.5; 8.6 +/ 0.9; 5.7 +/- 0.6, respectively; in control 13.8 +/- 1.5). The assumption that these effects are determined by factors originating from the regenerating liver was confirmed in experiments with double-layer agar systems. Inhibition of colony forming activity of PLS cells was the maximum in application of the hepatocytes of the rats which underwent a complex of effects, as a feeder, versus the hepatocytes taken in intact or hepatectomized animals, or the rats which were given RRE (number of colonies per plate well being 4.6 +/- 0.3; 15.7 +/- 1.6; 7.4 +/- 0.8; 8.7 +/- 0.9, respectively; in the control 25.6 +/- 6.5). In experiments on mice with Ehrlich adenocarcinoma, the factors isolated from the liver of animals subjected to PHE against a background of RRE administration and from the liver of mice which were given RRE only, as well as operated or intact ones, inhibited the tumor growth to 63, 38, 35 and 21%, respectively. PMID- 1857452 TI - Reaction to high-frequency electric impulses in two L cell sublines differing in high-frequency electric impedance and malignity. PMID- 1857453 TI - Endogenous nitrate synthesis in selected infectious diseases and ulcerative colitis. AB - Investigations into acute and chronic diarrheal patients confirmed the results of animal experiments on the role of cytotoxic activated macrophages in endogenous formation of nitrates. Because a number of inflammatory diseases did not cause a nitrate release in urine, blood, and saliva, the general importance of nitrates to characterize the initiation and course of inflammations must be questioned. PMID- 1857454 TI - Disorders in neuropsychological development and their relation to computed tomography brain scan in children with acute lymphoblastic leukemia in long-term remission. AB - In a group of 71 children with acute lymphoblastic leukemia in long-term remission lasting 4 to 15 years different disorders in their neuropsychological development were found. The disturbances observed were as follows: Emotional disorders in 88%, personality development disorders in 65%, mental retardation in 58%, signs of CNS dysfunction in 54%, and neurological disorder in 31% of children. Abnormal computed tomography brain scans were present in 49% of patients. They consisted mainly of two types: Hypodense areas of the white matter were observed in 23% and widening of the ventricular system and subarachnoidal spaces was present in 26% of children. Statistical evaluation showed significant relations between CT brain scan abnormalities (mainly hypodense changes) and neurological disorders as well as the presence of signs of CNS dysfunction and disorders of personality development. Emotional and mental changes did not correlate with abnormalities of CT brain scan findings. PMID- 1857455 TI - Breast cancer in Argentina: case-control study with special reference to meat eating habits. AB - An exploratory case-control study of the role of diet in the etiology of breast cancer was conducted in Buenos Aires, Argentina, where the mortality rate for this disease is high and the consumption of meat, mainly beef, is unusually elevated (76.2 kilograms per head were reported for 1987). One hundred and ninety six women with breast cancer admitted to the Institute of Oncology "Angel H. Roffo" and 205 controls were interviewed to obtain information on demographic, socio-economic and reproductive variables, on frequency of consumption of 40 food items, and on methods of cooking. Special emphasis was given to different kinds of meat. After controlling for other risk factors for breast cancer the major dietary associations observed were a statistically insignificant trend of increasing risk with amount of beef consumed, an increase in risk in women who ate more than 3 eggs per week, and an increase in risk in women who ate a variety of fried foods. PMID- 1857456 TI - [Neurologic complications after bone marrow transplantation]. AB - The retrospective study presented here reports clinical, electrophysiological and CT-data from 21 patients who underwent bone marrow transplantation for leukemia or aplastic anemia between 1980 and 1985. The aim of the investigation, which was performed at the end of 1986, was to elucidate whether antineoplastic drugs and radiation can result in long-term damage of the central nervous system. In 9 patients we observed neurological signs (1 leukencephalopathy, 5 cerebellar symptoms). Seven patients revealed dysrhythmia in the EEG and five had delayed latencies of visual evoked potentials. Eight patients exhibited pathological changes in CT (3 atrophy of supratentorial structures, 3 periventricular lucencies, 2 a combination of both). The results indicate that long-term damage to the CNS may be encountered after successful bone marrow transplantation. PMID- 1857457 TI - [Quantitative and qualitative MRI changes in temporal lobe epilepsy. A comparison with normal parameters of nuclear magnetic resonance tomography]. AB - Magnetic resonance imaging (MRI) often reveals no pathology in patients with temporal lobe epilepsy (TLE) who are candidates for surgery, even though post surgery histology reveals atrophy or sclerosis. To differentiate these pathologies in MRI, we performed a standardized acquisition and a quantitative analysis of MRI data (qMRI). The standard values of 43 healthy subjects (both sex, left and right handed) were compared with those of 10 patients with TLE and unilateral EEG focus. A reduced estimated total brain extension, a significant atrophy of both temporal lobes with accentuation on the focus side and a significant hippocampal atrophy on focus-side were seen even in patients with no visually detectable pathology. The analysis of the signal intensities did not give additional information. Thus, qMRI is a helpful additional tool in the course of presurgical evaluation for focus lateralization. PMID- 1857458 TI - [Cerebral hypersensitivity vasculitis]. PMID- 1857459 TI - [A case of cerebral thromboangiitis obliterans. Clinical and autopsy findings in Spatz and Lindenberg type I]. PMID- 1857461 TI - [Recommendations for clinical trials of drugs indicated for dementing diseases]. PMID- 1857462 TI - [Comments on the contribution by C. Wurthmann, M. Daffertshofer and M. Hennerici: Qualitative abnormal visceral sensations in multiple sclerosis. Nervenarzt 61:361 363 (1990)]. PMID- 1857460 TI - [Respiration-synchronous muscle activity in proximal arm and shoulder muscles after traumatic plexus and root lesions]. PMID- 1857463 TI - Adynamic bone disease in uremia: may it be idiopathic? Is it an actual disease? PMID- 1857464 TI - IgA nephropathy associated with Campylobacter jejuni enteritis. PMID- 1857465 TI - Subclavian vein stenosis, permanent cardiac pacemakers and the haemodialysed patient. AB - Two cases of subclavian vein stenosis secondary to permanent cardiac pacemakers are presented. Both stenoses were asymptomatic until arteriovenous fistulae/grafts were constructed in order to initiate haemodialysis. One patient experienced severe oedema of the arm which necessitated surgical closure of the graft. A literature review into major venous stenosis and cardiac pacemakers reveals an asymptomatic, but evidently underestimated, problem. As more elderly patients will be accepted onto haemodialysis programmes, this above-mentioned problem may become more common. Therapeutic answers as to haemodialysis access are discussed in these patients with permanent pacemakers who need haemodialysis. PMID- 1857467 TI - Production of interleukin-1 by mononuclear leukocytes and mesangial cells in experimental nephrotoxic nephritis. PMID- 1857466 TI - Hemodialysis and blood coagulation: the effect of hemodialysis on coagulation factor XIII and thrombin-antithrombin III complex. AB - Blood membrane interaction during hemodialysis (HD) regularly leads to stimulation of leukocyte function and related release of granular enzymes. The present study aimed to investigate the possible influence of an HD-induced release of granulocyte elastase on blood coagulation. Therefore a highly sensitive substrate of polymorphonuclear elastase, the plasma coagulation factor XIII and its subunits A and S were determined in the course of HD. Consumption of both subunit A and S have been previously shown to be due to proteolysis by elastase, whereas a decrease in subunit A will be typical for thrombin activation. Furthermore, the thrombin-antithrombin III complex (TAT) acting as a predisposition parameter for thrombotic events was measured during HD treatment. Apart from a virtual fall in factor XIII total activity simulated by heparin, no significant HD-induced consumption of factor XIII could be observed. There was also no indication of an elastase- or thrombin-related change in subunit concentrations. Predialysis values of the TAT complex were generally elevated in HD patients, but only patients with acute renal failure showed a constant increase of TAT during HD. These findings suggest that HD patients are exposed to a latent activation of coagulation resulting in an elevated thrombogenetic risk mainly due to the underlying disease. An additional coagulatory stimulation by the HD procedure seems to be restricted to cases of acute renal failure. PMID- 1857468 TI - A study of the effects of ipriflavone administration on hemodialysis patients with renal osteodystrophy: preliminary report. PMID- 1857469 TI - Cyclosporin neurotoxicity presenting as an unilateral foot drop in a renal transplant patient. PMID- 1857470 TI - Wedge-shaped low-density lesion on sonography of the kidney in advanced cirrhotic patient. PMID- 1857471 TI - Hemodialysis with a Permcath kept open with streptokinase and later citrate in a heparin-sensitive patient. PMID- 1857472 TI - Carcinoma of the kidney presenting as sterile peritonitis in a patient on continuous ambulatory peritoneal dialysis. PMID- 1857473 TI - Mode of progression of secondary hyperparathyroidism in patients with chronic renal failure. PMID- 1857474 TI - Horseshoe kidney, focal and sclerosing glomerulonephritis and primary hypothyroidism. PMID- 1857475 TI - Comparison of methylguanidine production from creatinine and creatol in vivo. PMID- 1857476 TI - Impairment of amino-induced renal hyperemia in pancreatectomized dogs. PMID- 1857478 TI - Effects of dipyridamole on the short-term evolution of glomerulonephritis. AB - The aim of the present study is to evaluate the effect of dipyridamole (300 mg/day) versus placebo in a double-blind randomized trial on membranous glomerulonephritis (M-GMN), mesangial IgA glomerulonephritis (IgA-GMN), and segmentary and focal hyalinosis glomerulonephritis (SFH-GMN) during the first 3 months of treatment. In the case of M-GMN, proteinuria dropped by 60% of the basal value in patients treated with dipyridamole; in the case of IgA-GMN it dropped by 65-70%; and in the case of SFH-GMN it dropped by 40% of the basal value. Inhibition of proteinuria in M-GMN was correlated to platelet response, and above all, to the ADP-induced platelet aggregation in whole blood. PMID- 1857477 TI - Tubulointerstitial nephritis and Mediterranean spotted fever. PMID- 1857479 TI - Urinary albumin excretion in patients with non-insulin-dependent diabetes mellitus in an early microalbuminuric stage. AB - We investigated the urinary albumin excretion and renal hemodynamics of normotensive nonobese patients with impaired glucose tolerance (IGT) and non insulin-dependent diabetes mellitus (NIDDM) in an early microalbuminuric stage (defined by albuminuria less than 30 mg/day). In comparison with normal subjects, a significant increase in urinary albumin excretion was observed already in the IGT stage [U-albumin/U-creatinine: NL (20 subjects), 5.3 +/- 1.7 mg/g Cr; IGT (23 subjects), 11.9 +/- 6.7 mg/g Cr; DM (20 subjects), 12.8 +/- 5.7 mg/g Cr]. A 3 week diet therapy combined with physical exercise prescribed for 53 normotensive non-obese mild NIDDM patients resulted in improvement in glucose tolerance, concomitant with lowered systemic blood pressure and a decrease in urinary albumin excretion (SBP: 128.4 +/- 13.0 to 106.4 +/- 10.2 mm Hg, p less than 0.01; DBP: 78.2 +/- 10.8 to 66.0 +/- 8.0 mm Hg, p less than 0.01; U-albumin: 19.4 +/- 10.3 to 10.1 +/- 9.1 mg/day, p less than 0.01). However, glomerular filtration rate, renal plasma flow, filtration fraction and urinary beta 2-microglobulin excretion remained unchanged. From these results, we hypothesized that focal glomerular hyperperfusion increases urinary albumin excretion in patients with early NIDDM. PMID- 1857480 TI - Desferrioxamine enhances the haemopoietic response to erythropoietin, but adverse events are common. AB - To determine whether the chelation of aluminium enhances the haemopoietic response to recombinant human erythropoietin (r-HuEPO), desferrioxamine (DFO) at a dose of 20-30 mg/kg was given to 7 of 17 transfusion-dependent haemodialysis patients treated with r-HuEPO (40 units/kg/dialysis i.v.). The two randomly allocated groups did not differ in age, initial haemoglobin, plasma aluminium, plasma aluminium after DFO challenge, and ferritin, but, by chance, dialysis time was longer in the DFO group (69 vs. 32 months; p = 0.02). DFO was administered for 16 +/- 4 (SE) dialyses. During this period, Hb rose faster in the DFO group, in relation to time (0.61 vs. 0.29 g/l day; p less than 0.05) and r-HuEPO dose (3.35 vs. 1.88 g/l/100 units r-HuEPO/kg; p less than 0.05). However, in the DFO group, there was a high incidence of side effects, especially visual toxicity. It is concluded that DFO enhances the effectiveness of r-HuEPO in correcting the anaemia of chronic renal failure, but the combination of DFO and r-HuEPO is unsafe under the conditions described. PMID- 1857481 TI - Total and split renal function assessed by ultrasound Doppler techniques. AB - We evaluated total and split renal functions from the pattern for renal arterial blood flow detected by ultrasound Doppler in healthy subjects and patients with varying degrees of renal function and disorders other than renovascular hypertension or severe aortic valvular disease. A renal-time pulsed ultrasonic echo-Doppler device at 2.5 MHz was used with a translumbar approach. The ratio of peak diastolic (D) to systolic (S) velocity correlated well with both p aminohippurate clearance and creatinine clearance. Acceleration time was correlated with the clearance of neither compound. To evaluate the clinical usefulness of ultrasound Doppler in the assessment of split renal function, we compared the D/S ratio with the renal function obtained by radionuclide methods for individuals. The split renal glomerular filtration rate, calculated by a method which makes use of the early renal uptake of 99mTc-diethylenetriam inepentaacetic acid, correlated well with the D/S ratio. These results indicate that the ultrasonic measurement of renal arterial blood flow by the pulsed Doppler method should be useful for assessment of total and split renal functions. PMID- 1857482 TI - Comparative effects of enalapril, atenolol and chlorthalidone on blood pressure and kidney function of diabetic patients affected by arterial hypertension and persistent proteinuria. AB - Arterial hypertension and proteinuric nephropathy are common features in diabetic patients. In streptozotocin-diabetic rats, it has been possible to reduce the blood pressure and proteinuria by converting enzyme inhibitors, and so slowing the decline of kidney function. These results have been confirmed in diabetic patients affected by arterial hypertension and persistent proteinuria. However, up to now it has not been clear if these favorable renal effects are related specifically to converting enzyme inhibition. In the attempt to clarify this last point, from a practical as well as from a speculative point of view, 12 type 2 diabetic outpatients affected by mild to moderate arterial hypertension and persistent macroalbuminuria (greater than 250 mg/daily, at least on three consecutive occasions) without any other signs of renal diseases were studied. In a randomized sequence and in a double blind fashion, after a washout period of 3 weeks, the patients underwent pharmacological treatment which consisted of enalapril 20 mg o.d., chlorthalidone 12.5 mg o.d., atenolol 50 mg o.d. and placebo o.d. Each treatment lasted 45 days. Kidney function, blood pressure and heart rate were checked at the beginning and at the end of each treatment, while urinary albumin excretion was measured at the end of the 4th, 5th, and 6th week of each treatment. Blood pressure significantly decreased in a similar fashion after each active treatment, while kidney function did not change significantly. Urinary albumin excretion rate significantly decreased after enalapril and atenolol, but did not change after chlorthalidone. According to these results we can hypothesize that the inhibition of tissue angiotensin formation and its related change on the glomerular permeability, rather than renal and systemic hemodynamic features, seem to be the common mechanisms by which both enalapril as well as atenolol decrease the albuminuria in our patients. PMID- 1857483 TI - Short-term effects of calcium antagonists on renal haemodynamics in patients with chronic renal failure. AB - Experimental evidence suggests that pharmacological manipulations of glomerular haemodynamics may affect the progression of chronic renal insufficiency and scarring. In this study, we have investigated the short-term (4 weeks) renal haemodynamic effects of nifedipine and nitrendipine (10 mg/thrice daily) in two separate groups of 6 patients with stable chronic renal failure (CRF) (glomerular filtration rate, GFR: 9.7-47.8 ml/min/1.73 m2). Patients were studied on three occasions: (1) before the administration of the calcium antagonist, (2) after 4 weeks of treatment and (3) 4 weeks after the discontinuation of the drug. Mean arterial pressure fell significantly on nifedipine: from 116.33 +/- 12.25 to 107.22 +/- 18.67 mm Hg, p less than 0.05, and on nitrendipine: from 112.22 +/- 10.04 to 102.22 +/- 13.77 mm Hg, p less than 0.05. There was no significant effect of either calcium antagonist on GFR, effective renal plasma flow (ERPF), proteinuria or natriuresis. Consequently, renal vascular resistance (RVR) fell in both experimental groups, nifedipine: from 51.40 +/- 28.77 to 44.97 +/- 30 dyn s cm-5 x 10(3) (mean +/- SD), and nitrendipine: from 37.04 +/- 18.46 to 30.47 +/- 15.56 dyns s cm-5 x 10(3), p less than 0.05. These results show that calcium antagonists reduce systemic blood pressure whilst GFR and ERPF are maintained. The fall in the RVR of patients with CRF treated with calcium antagonists may confer on these agents a therapeutic advantage in the management of progressive renal insufficiency. PMID- 1857484 TI - Cisplatin nephrotoxicity in cadmium-pretreated rats. Enzymatic, functional and morphological studies. AB - Treatment of rats with cisplatin or with cisplatin after chronic pre-exposure to cadmium induced a decrease in kidney cytochrome P-450 and glutathione levels, and in glutathione peroxidase and reductase activities. Furthermore, cadmium and cisplatin enhanced lipid peroxidation, oxidized glutathione and N-glucuronyl transferase activity. Glutathione S-transferase (substrate: 1-chloro-2,4 dinitrobenzene) was increased and decreased by cadmium and cisplatin respectively. On morphological observation, cadmium nephrotoxicity was characterized by tubular proximal damage with mitochondrial and lysosomal changes and a widespread vesiculation of tubular cells. A marked focal tubular necrosis associated with cyst formation was observed in cisplatin nephrotoxicity. On the basis of the measured biochemical, functional and histological parameters, it is concluded that cadmium pretreatment did not potentiate the nephrotoxic effect of cisplatin. PMID- 1857485 TI - Isolation and characterization of chicken mesangial cells. AB - Experimental autoimmune glomerulonephritis (EAG) in chickens appears to be mediated by cellular immunity and is associated with mesangial proliferation. We have developed techniques for the culture of chicken mesangial cells to study factors in vitro which lead to this proliferation. Chicken glomeruli isolated by sieving collagenase-treated whole kidney homogenates were cultured in Waymouth's medium MB 752/1 supplemented with 20% decomplemented fetal calf serum and 1 unit/ml insulin. Propagated cells share the following characteristics with mammalian mesangial cells: stellate and spindle-shaped morphology with an extensive microfilamentous system by light and electron microscopy; resistance to aminonucleoside of puromycin; susceptibility to mitomycin C; growth in L-valine free medium; absent staining for factor VIII-related antigen, chicken T cell and Ia antigen; positive staining for fibronectin, myosin, alpha-actinin and desmin, and angiotensin II binding and induction of contraction. Unlike cultured mammalian mesangial cells, chicken mesangial cells avidly phagocytize latex beads and display multilamellar residual bodies on electron microscopy indicative of phagocytic activity. They differed from fibroblasts which were non-phagocytic, had different growth patterns, fluorescence staining and ultrastructural morphology. To our knowledge, this is the first description of the culture of chicken mesangial cells. This in vitro system should allow further studies of pathogenetic processes involved in the production of EAG with elucidation of mechanisms relevant to human disease. PMID- 1857486 TI - Studies on the precursor of methylguanidine in rats with renal failure. AB - Each of creatinine (Cr), guanidinoacetic acid (GAA) and arginine (Arg) was administered intraperitoneally to rats with renal failure, and the levels of methylguanidine (MG) in the serum, liver, kidney, muscle and urine were determined at certain intervals. The levels of MG in the serum, liver, kidney, muscle and urine after Cr administration increased markedly with time. The amount of total MG at 24 h was estimated to be 114 micrograms/100 g body weight, which accounted for 0.46% of the Cr dose. In contrast, changes in MG levels after administration of GAA or Arg were only slight in comparison with those after Cr administration. Thus, MG was proved to be produced mainly from Cr. PMID- 1857487 TI - The lowering effect of probucol on plasma lipoprotein and proteinuria in puromycin aminonucleoside-induced nephrotic rats. AB - Hyperlipidemia associated with nephrotic syndrome was treated with probucol and the changes in plasma lipoprotein lipid concentration and urinary protein excretion were examined in puromycin aminonucleoside-induced nephrotic rats. Rats made nephrotic exhibited severe hyperlipidemia with increases in all major lipoprotein fractions. Probucol treatment of nephrotic rats significantly lowered plasma triglyceride (TG), cholesterol (Ch) phospholipid (PL) and apoprotein B associated with very-low-density and low-density lipoprotein and Ch and PL in high-density lipoprotein (HDL). Malondialdehyde (MDA) associated with the lipoproteins was significantly elevated in nephrotic rats and probucol treatment also lowered MDA concentration in all major lipoproteins. In control rats probucol moderately, but significantly, reduced plasma TG and HDL-Ch concentrations. Proteinuria associated with nephrosis was decreased significantly by treatment with probucol. Probucol treatment did not affect blood urea nitrogen and plasma creatinine levels. A significant positive correlation existed between the amount of protein excreted in urine and the plasma lipid concentrations in all nephrotic rats, suggesting that the hypolipidemic effect of probucol may attenuate proteinuria associated with nephrosis. These results suggest that probucol may be a favorable treatment for hyperlipidemia associated with nephrotic syndrome. PMID- 1857488 TI - Propionic acidaemia: a neuropathological study of two patients presenting in infancy. AB - The clinical and neuropathological findings are described in two children with propionic acidaemia presenting in infancy; they survived for 4 and 16 years respectively. Abnormalities were noted in the basal ganglia of both patients. In one child who clinically had severe athetosis, there was marbling of the corpus striatum. Clinical and morphological evidence suggests that the basal ganglia are especially vulnerable in propionic acidaemia. PMID- 1857489 TI - Heat shock in cultured neurons and astrocytes: correlation of ultrastructure and heat shock protein synthesis. AB - Cultured cerebral cortical neurons and astrocytes were compared after a brief shock. Morphological findings were correlated with the synthesis of the 68 kD heat shock protein (HSP68). Heat shocked neurons demonstrated many severe morphological changes after exposure to temperatures of 43 degrees C for 15 min and 45 degrees C for 10 min. Nuclear membrane 'blebbing' with lysis of the membrane, chromatin clumping, and disappearance of the nucleolus were prominent after both conditions. Lysis of the cell membrane was noted in severely injured neurons; this was more prominent at the higher temperature. In addition, alterations to polyribosomes, Golgi apparatus, rough endoplasmic reticulum and mitochondria were noted in the cytoplasm of neurons after heat shock. In contrast, no significant changes were noted in either the nucleus or cytoplasm of heat shocked astrocytes. The severity of morphological changes in neurons directly correlated with the low level of induction of HSP68 in neurons. Neurons synthesized much less 68 kD heat shock protein than similarly heat shocked astrocytes. We conclude that cultured cerebral cortical neurons are more susceptible to injury after heat shock than heat resistant astrocytes and that one possible mechanism of injury is failure to synthesize adequate amounts of HSP68 after injury. PMID- 1857490 TI - Multifocal multinucleated giant cell myelitis in an AIDS patient. AB - A 19-year-old male intravenous drug abuser, was admitted to hospital with a one week history of lower limb weakness and urinary retention. He was known to have been HIV-seropositive for 3 years and had been treated for cerebral toxoplasmosis. Neurological examination confirmed flaccid paraparesis with weak ankle jerks and bilateral extensor plantar responses. There was no obvious sensory deficit. Neurological examination was otherwise normal. CSF contained 63 mg/dl protein and 10 leucocytes/mm3. Myelography was normal. He died 1 month later from septic peritonitis. Neuropathological examination showed chronic lesions of toxoplasmosis in brain. Small necrotic foci with myelin loss, proliferation of microglia, macrophages and multinucleated giant cells (MGC) were disseminated in the whole spinal cord, mostly in the white matter, but the brain was spared. Immunohistochemistry demonstrated p24 and p17 HIV antigens in macrophages, MGC and microglial cells. These lesions resemble those of so called 'multifocal giant cell encephalitis'. The present case demonstrates that HIV related multifocal inflammatory changes may be restricted to the spinal cord and may be a cause of myelopathy in AIDS patients. PMID- 1857491 TI - Neurotoxic acrylamide and neurotrophic melanocortin peptides--can contrasting actions provide clues about modes of action? AB - Experimental acrylamide neuropathy has been studied as a model of degenerative neurological disorders of the 'dying-back' type for over 30 years. Functional, histological, ultrastructural, electrophysiological and biochemical aspects of acrylamide neuropathy have been described and several hypotheses concerning the mode of action proposed. However, the mechanism whereby acrylamide causes axonal degeneration and inhibits nerve sprouting remains unknown. By analogy with agonist/antagonist comparisons used by the pharmacologist, we have reconsidered the acrylamide problem in the light of the opposite effects summarized in Table 1, of neurotrophic peptides related to ACTH/MSH (collectively termed melanocortins). The contrasting effects on sprouting and the eventual quality of repair of mechanically lesioned nerves have suggested a mechanism whereby sprouting may regulate perikaryal adjustments to injury. We have also posed the question as to whether a common biochemical mechanism, namely selective proteolysis of neurofilament protein may underlie the opposing effects of acrylamide and melanocortins on nerve sprouting. This possibility implies a hitherto unknown role for neurofilament protein turnover in neuronal maintenance and repair, a suggestion that may provoke further research and discussion. PMID- 1857492 TI - Canavan disease: value of N-acetylaspartic aciduria? PMID- 1857493 TI - Prenatal stroke suggested by intrauterine ultrasound and confirmed by magnetic resonance imaging. AB - Cerebral infarction is rare in premature newborns and is most commonly the result of arterial embolization from the placenta. A focal echodense area was identified on prenatal cranial ultrasonography (US) in a premature infant (34 weeks of gestation). After birth, cerebral infarction was confirmed by magnetic resonance imaging (MRI). The clinical findings, imaging findings and pathogenesis are discussed. New diagnostic methods such as MRI show to be a useful approach in the neonatal period facilitating recognition of cerebrovascular accidents also in low birth-weight infants. PMID- 1857494 TI - Juvenile onset diabetes mellitus, central diabetes insipidus and optic atrophy (Wolfram syndrome)--neurological findings and prognostic implications. AB - The authors report on one case of Wolfram syndrome, a rare condition, which is characterized by juvenile onset diabetes mellitus, diabetes insipidus, optic atrophy and sensorineural deafness. The findings of this 13-year follow-up show that this patient developed typical neurological complications of long-standing diabetes mellitus as in the common type 1 variant. Moreover, some peculiar signs occurred such as anosmia, ophthalmoplegia interna, and central nystagmus. Since Wolfram syndrome is probably part of a more generalized neurodegenerative disorder, long-term prognosis will depend both upon the severity of chronic diabetic complications and upon the rapidity, by which degeneration of cerebellar, pontine and brain stem structures appear. Prognosis of the cardinal clinical signs is such that optic atrophy, though usually quite rapid in the beginning, generally does not lead to complete blindness. Sensorineural hearing loss progresses very slowly so that deafness might be expected exceptionally only. The hearing deficit in classical diabetics, however, is of retrocochlear origin. Therefore, in Wolfram syndrome, a combined inner-ear and retrocochlear hearing loss may occur. PMID- 1857495 TI - Fusarium meningoencephalitis in a child with acute leukemia. AB - A 15-year-old boy with acute lymphoblastic leukemia (ALL) developed disseminated fusarium infection with meningoencephalitis following a contaminated skin wound. With antifungal therapy, the cutaneous lesions cleared but central nervous system (CNS) infection persisted causing a fibrosing meningitis and a brain granuloma. Fusaria are soil saprophytes that are more commonly associated with superficial eye and skin lesions, but may also cause severe systemic infections with CNS involvement in immuno-compromised patients. The organism may be confused with Aspergillus in tissue sections, and can only be diagnosed by culture. PMID- 1857496 TI - Infantile hereditary neuropathy with hypomyelination: report of two siblings with different expressivity. AB - We report the cases of two siblings both affected by inherited sensory-motor neuropathy of a demyelinative nature but with markedly different severity and pathological findings. The clinical, neurophysiological and morphological features in these two cases were consistent with the diagnosis of Hereditary Motor Sensory Neuropathy type 3 (HMSN 3), according to the classification of Dyck, with different expressivity. These results raise the still unsettled question of the phenotypic variants in inherited neuropathies. In fact the most severely affected of our cases had clinical and neurophysiological findings identical to those reported in cases of Congenital Hypomyelination Neuropathy (CHN), but the morphological picture in the sural nerve was inconsistent with this diagnosis. The criteria for the diagnosis and the reported cases of CHN have been reviewed. PMID- 1857497 TI - Pelizaeus-Merzbacher disease: classical or connatal? AB - The clinical features and investigation results of 7 patients with Pelizaeus Merzbacher disease (PMD) are described; one patient had a brain biopsy and two patients had an autopsy. This paper tries to differentiate the clinical features of the connatal and classical types of PMD. Transient stridor and nystagmus were early signs in both types of PMD. Our findings support the view that the more severe connatal form shows rapid neurological deterioration from an early age leading to death usually in the first decade. In younger patients in whom the evolution is still unclear, severe feeding problems and extrapyramidal features may suggest the connatal form. By contrast, in the classical form of PMD, cerebellar signs and cognitive deterioration are more prominent with a more slowly progressive course. Nuclear magnetic resonance imaging and brainstem auditory evoked potentials were very helpful in supporting the diagnosis of PMD either in a known affected family or in sporadic cases, but were not useful in distinguishing between the two types of PMD. Genetic counseling in this condition is difficult, particularly in the connatal form in which inheritance may be either X-linked or autosomal recessive. PMID- 1857499 TI - Effects of behavioural state on visual processing in neonates. AB - Assessment of visual capacity in full-term neonates as a function of behavioural state was investigated with the luminance flash visual evoked potential (VEP). Infant state (quiet sleep, active sleep, quiet wakefulness, active wakefulness) was determined by behavioural observation and polygraphic recording of EEG, eye movements, electrocardiogram, electromyogram and respiration. VEPs were recorded across the sleep/waking cycle only under carefully defined state conditions. The results indicate that state dramatically effects the amplitude, latency and waveform of the transient luminance flash VEP with the most significant differences between sleep and wakefulness. The results further suggest that controlled state recording reduces intra and intersubject VEP variability. PMID- 1857500 TI - Mental planning and anticipatory processes with acute and chronic frontal lobe lesions: a comparison of maze performance in routine and non-routine situations. AB - A series of computerized mazes were masked during presentation allowing only partial view of their structure. Patients suffering from acute or chronic unilateral frontal (medial, lateral) or retrorolandic (temporal, parietal) lesions and non-brain-damaged controls were required to pass through the mazes repeatedly, until they solved them without reaching a dead end. Because the mazes could not be viewed in their entirety at any one time, the subjects were forced to mentally generate and apply a plan of the maze. The first ("non-routine" situation), the second and the last ("routine" situation) trials of the mazes were analysed separately. The prefrontal cortex is supposed to subserve important functions in the planning of behaviour in unfamiliar, non-routine situations. Shallice (Phil. Trans. R. Soc. Lond. B298, 199-209, 1982; From Neuropsychology to Mental Structure, Cambridge University Press, Cambridge, 1988) therefore postulated that the behaviour of patients with frontal lobe lesions should not be disturbed in routine situations, but rather these patients should exhibit difficulties in dealing with new and unfamiliar situations. In the present investigation, patients with acute and chronic frontomedial lesions exhibited deficits in generating mental plans. Patients with acute frontomedial lesions made a larger number of errors in their second trials and subsequently required more trials to reach task criterium. Patients with chronic frontomedial lesions showed more frequent rule-breaking behaviour in their second trials. The analysis of maze performance in the first trial and that trial in which task criterion was achieved, showed that frontal lobe patients were impaired in neither routine nor non-routine situations. The observed results suggest a modification concerning Shallice's assumptions. Patients with frontomedial lesions are not generally incapable of dealing with non-routine situations. But they seem to be slower than patients with retrorolandic lesions and controls in profiting from experiences made in an unfamiliar, non-routine situation represented by the first explorations of new maze problems. This deficit can possibly be explained by the observation that anticipatory processes or the formation of expectations about possibly correct decisions in non-routine situations were altered in acute and chronic frontomedial patients. When these patients reached a maze intersection for the first time and therefore had no information about the continuation of the correct path, they showed significantly different intuitive directional decisions when compared to controls. PMID- 1857501 TI - Generative associative naming in dementia of Alzheimer's type. AB - Forty-eight patients with mild to moderate dementia of Alzheimer's type (DAT) were tested with a generative associative naming task, a task that combines the aspects of fluency and of word association tests. The variables taken into consideration were the number of adequate and inadequate responses, conventionality, word frequency and lexical-semantic relation to the target. DAT patients' performances were compared to those of a group of control subjects matched for sex, age and educational level. As a group, the patients gave fewer adequate responses, more idiosyncratic responses and perseverations, while there was no difference in the qualitative variables. However, the analyses of the performance profiles suggest that, irrespective of the severity of the disease, two major subgroups of DAT patients may be identified: (1) a first subgroup of subjects produced words with a lower conventionality rate and these were mostly in propositional relationship to the target; they also produced a higher rate of idiosyncratic responses and perseverations. (2) A second subgroup of subjects gave more conventional responses, mostly in the hierarchical-categorical relationship. The disorders of the former subgroup seem to correspond to a disrupted access to some relatively spared semantic abilities, whereas those of the latter to a semantic breakdown. PMID- 1857498 TI - Non-target visual event-related potentials in evaluation of children with minor head trauma. AB - In 50 children, 4 months to 12 years of age, with minor head trauma non-target visual event-related potentials were performed and compared to a second registration of the potentials some months later. On following-up there was a clear tendency for a relative improvement of the latencies of the endogenous potentials. In this way non-target visual event-related potentials proved to be of value in the investigation of mental impairment in early childhood. PMID- 1857502 TI - Different pattern of hemisphere specialization between identical kinesthetic spatial and weight discrimination tasks. AB - Thumb position discrimination and weight discrimination tasks were examined in female students. Task procedures were identical for the position and weight tasks. Different weights were loaded for each positioning and the thumb was abducted to discriminate the weight. The Weber ratio was obtained by the method of constant stimuli and was compared between right and left. The results of position discrimination indicated left thumb (right hemisphere) superiority, while the results of weight discrimination indicated no laterality despite identical tasks. Directed attention is suggested to play an important role in the appearance of hemisphere lateralization. PMID- 1857503 TI - Musical priming by the right hemisphere post-callosotomy. AB - The hemispheric representation of auditory functions mediating the perception of harmony in music was investigated in two split-brain patients using a musical chord priming task. Previous experiments in normal subjects had demonstrated that the harmonic context established by a prime chord influences the accuracy of target chord intonation judgements. Only the right hemisphere of each callosotomy patient manifested the normal interaction between harmonic relatedness and intonation. The results raise the possibility that associative auditory functions which generate expectancies for harmonic progression in music are lateralized within the right hemisphere. PMID- 1857504 TI - Left out axons make men right: a hypothesis for the origin of handedness and functional asymmetry. AB - The origin and underlying mechanisms of hand preference are still unresolved, despite extensive research and discussion. Numerous possibilities have been considered, including genetic and hormonal factors, brain insult and learning. We suggest here that naturally occurring loss of axons of the corpus callosum (either symmetric or asymmetric, with or without neuron death) may be one mechanism underlying the embryological development of hand preference and hemispheric anatomical and functional asymmetries in males. We note supporting evidence for this hypothesis from a report of increased prevalence of left handedness in children born prematurely at the gestational age prior to the likely onset of axon loss. The practical implications of this hypothesis for clinical management in neonatal intensive care units are discussed. It is suggested that the course of loss of callosal axons may have a genetic component which is associated with a sex-related influence and which is modifiable by prenatal and early postnatal events. PMID- 1857505 TI - Visual field asymmetries for pattern processing are present in infancy. A comment on T. Hatta's study on children's performances. AB - From a study on 4 to 6 year-old children, Hatta (Hatta, Neuropyschologia 28, 1053 1062, 1990) concludes that (a) a left visual-field advantage develops at age 4 to 5 years in visuo-spatial stimulus recognition, and (b) since both the right visual-field advantage for verbal and the left visual-field advantage for visuo spatial material develop at the same age, there is no support for the claim that the left and right hemispheres develop differentially. We contest these conclusions on the basis of our own infant studies which have shown a right visual-field advantage in 4 to 9 month-old infants for individual face recognition and more recently, for some aspects of visual patterns. PMID- 1857506 TI - Developmental changes in finger localization. AB - This experiment examined the basis for developmental changes in finger localization performance. Groups of children aged 6, 8 and 10 years were tested on an uncrossed localization task and a crossed localization task or a model localization task. In the uncrossed localization task they used the stimulated hand to localize the stimulated fingers on the stimulated hand. In the crossed localization task they used the unstimulated hand to localize the stimulated fingers on the unstimulated hand. In the model localization task they used the stimulated hand to localize the stimulated fingers on a model hand. Localization for the uncrossed task was more accurate than for either the crossed or model tasks, but developmental differences in localization accuracy were comparable for each of the three localization tasks. The present results do not support the suggestion (Galin et al., Brain Lang. 4, 588-590, 1977; Quinn and Geffen, Neuropsychologia 24, 793-804, 1986) that developmental changes in crossed localization result from changes in the efficiency of interhemispheric transfer of information. PMID- 1857507 TI - [Behavior of systolic blood pressure during recovery phase after bicycle ergometric test. Its value in the diagnosis of ischemic heart disease]. AB - The diagnostic utility of an abnormal decrease in systolic blood pressure (PAS) after exercise, have been evaluated by an index obtained by the ratio between PAS at the maximal stage of exercise and PAS at the 1', 3' and 5' of recovery (PAS index). The 58 patients studied have been divided in two groups: group A, 32 patients, aged 33-66 (means 51.5) with angina pectoris and significant coronary stenosis; group B, 26 subjects, aged 27-39 (mean 34.7), asymptomatic, without coronary stenosis (control group). PAS index at 1' of recovery have been 0.82 +/- 0.08 in the group B and 0.94 +/- 0.07 in the group A (p less than 0.0005); at the 3' of recovery 0.72 +/- 0.07 in the group B and 0.86 +/- 0.11 in CAD group (p less than 0.0005); at 5' of recovery 0.66 +/- 0.07 in the group B and 0.79 +/- 0.11 in the group A (p less than 0.0005). Diagnostic accuracy have been of 60%, 75% and 75% for PAS index respectively at first, third and fifth minute of recovery, while ST depression diagnostic accuracy have been of 88%. PMID- 1857508 TI - [Dysplasia of the right ventricle]. AB - The end of this work is to talk about a relatively new disease: right ventricular dysplasia (RVD). The Authors consider clinical and instrumental features of the illness with particular reference to recent data for histopathological and instrumental diagnosis. Most interesting are the electron microscopy observations and, above all, nuclear resonance magnetic (NMR) findings. PMID- 1857510 TI - [Cardiac malformations with septal defects. Apropos of a case of biloculate heart with transposition and aortic atresia]. AB - The Authors describe a case of uniatrial univentricular heart with a right transposition and atresia of the aorta. This case forms part of an autoptic series of 74 congenital cardiopathies with defects of the septal system: monometameric (52 cases), polymetameric (22 cases), and limited (66 cases) or broad DIA, DIV or FAP types (8 cases). Having outlined the correlations between the type of defect and the complex morphogenetic events, whose close integration leads to a continuous septal system, the Authors focus their attention on the common associations between septal defects and other cardio-vascular anomalies (66 cases). The analysis of findings supports hypothesis that many of these are due to alterations in the position and direction of individual septal buds are should be seen against the overall background of septal pathology. Under these circumstances the pathogenetic importance of alterations of the complex movements presented by the cardiac type during the course of septal development and, to an event greater extent, possible alterations of the embryonal hematic flow are underlined. PMID- 1857509 TI - [Non-invasive temporary cardiac pacing. Possibilities and limitations]. AB - The non-invasive temporary pacemaker is a reliable and easy method for emergency treatment of asystole or severe bradycardias. Large electrode areas and long pulse width allow a low stimulation threshold (40-60 mA), and so were largely eliminated discomfort resulting from contraction of skeletal muscles and burning pain from stimulation of cutaneous nerves. In our experience, non-invasive pacing was effective in all thirteen patients in whom it was applied, was maintained for a mean time of 30 minutes and then temporary endocardial pacing was performed. In our opinion, this method will be a valid alternative to transvenous pacing, when completely eliminated stimulation of skeletal muscles and cutaneous nerves. It may play a role in the treatment of tachyarrhythmias. PMID- 1857511 TI - [Concurrence of intra-atrial conduction disorders in the initiation of paroxysmal atrial fibrillation]. PMID- 1857512 TI - [Supraventricular tachycardia with PR interval shorter than RP interval. Electrogenetic mechanisms and diagnostic criteria]. AB - The Authors report their experience on the different clinical electrocardiographic patterns of tachycardias with P'R interval shorter than RP'. The electrocardiographic criteria, in basal conditions and after autonomic stimulation, and the role of electrophysiologic study, particularly in transesophageal way, are discussed. Finally the Authors propose a noninvasive diagnostic algorithm for a correct clinical approach. PMID- 1857513 TI - [The eye and pregnancy]. AB - The principal effects of pregnancy on the eye are reviewed, these effects being subdivided into three main sections: paraphysiological changes, pathological conditions developing in pregnancy and related to it, pre-existing pathological conditions that are to some extent altered by pregnancy. On the basis of the data supplied, a continuous, increasingly assiduous clinico-experimental give-and-take between oculist and gynaecologist is recommended to prevent possible eye complications. PMID- 1857514 TI - [Therapy of pre-invasive forms of the portio cervicis. Personal experience]. AB - The Authors report their personal experience of the treatment of dysplasia of the portion over the past 5 years. Out of a total sample population of 286 patients, 31.1% received conservative therapy (deep DTC) and 68.9% underwent conisation or total hysterectomy. Follow-up ranged between 24 and 48 months and revealed a similar incidence of relapse in both the deep DTC and conisation groups. The study was limited by the progressive decrease in the number of patients who attended regular check-ups. PMID- 1857515 TI - [Presenile and senile vulvovaginitis. Topical hormonal treatment with estriol]. AB - A population of 39 women (average age 64.5 years) suffering from presenile or senile vulvovaginitis was subjected to topical treatment with oestriol-based vaginal cream (daily applications of 0.50 mg of oestriol corresponding to 4 g of cream for 14 days and three times a week in the three following weeks). The results of treatment were assessed on the basis of the clear-cut improvement in symptomatology and the noteworthy increase in the index and volume of maturation of the vaginal epithelium. The effectiveness of topical treatment of postmenopausal vulvovaginitis with oestriol in the absence of unwanted side effects is confirmed. PMID- 1857516 TI - [The Gemeprost test in the screening of endometrial pathology]. AB - A randomized clinical trial has been performed to evaluate the efficacy of intravaginal 1 mg Gemeprost for pre-operative cervical dilatation prior to vacuum aspiration and curettage for endometrial biopsy. Eighty-nine patients were evaluated, 51 treated with Gemeprost and 38 with placebo: in the first group biopsy was possible in 94% of cases vs 86% in the second group. Pain was significantly reduced with Gemeprost improving the success rate and the patient compliance. PMID- 1857517 TI - [Management of cervico-vaginal dystrophies]. AB - Fifty-nine outpatients affected by cervico-vaginal dystrophy with manifest symptoms were included in the study. Following initial tests (colposcopy with Schiller's test, colpocytological test, analysis of symptoms), a cycle of treatment was commenced using the insertion of a vaginal pessary of Polydeoxy ribonucleotide (PDRN) in the evening for 20 days. A control on day 28 revealed a marked improvement of the symptoms together with a positive evolution of objective tests. During the 10th week after the end of therapy, both subjective and objective findings tended to confirm the relapse towards pre-treatment conditions. PMID- 1857518 TI - [Preliminary study of the use of s. adenosyl methionine in the management of male sterility]. AB - In a preliminary study 10 cases of male sterility were treated with 800 mg/day per os of Samyr-Bioresearch over three months. Increased basal motiligy of spermatozoa was observed in 6 out of 10 cases. The results of the study confirm the value and efficacy of SAM in the treatment of male sterility. PMID- 1857519 TI - [Monitoring of protracted pregnancy. Comparison of two methods]. AB - Antepartum cardiotocographic patterns (NsT:Nonstress Test) and echographic assessments of amniotic fluid pockets were retrospectively analysed in 63 postdate pregnancies. The results of NsT (Fisher-score) and ecographic examinations were correlated with obstetric outcome (5 minutes Apgar-score). Ecographic assessments of amniotic volumes seem more effective than NsT for the lower frequency of false-positive results. Anyhow, considering the low sensibility of NsT and Echography separatedly considered, the Authors suggest a simultaneous valuation of the two tests. PMID- 1857520 TI - [Ultrasonic diagnosis of anencephaly during the 15th week of pregnancy]. AB - The Authors describe a case of anencephaly diagnosed by ultrasound in the XV week of pregnancy. They confirm the importance of anamnesis to single out the persons at risk, but emphasize the validity of ultrasound for the chance diagnoses. PMID- 1857521 TI - [Soranus of Ephesos and methodism. A gynecologist of the 2nd century A.D]. PMID- 1857522 TI - Action of rHuEpo on mechanical membrane properties of red blood cells in children with end-stage renal disease. AB - By means of a micropipette aspiration technique mechanical membrane properties of RBC in ten uraemic children undergoing haemodialysis were compared to those of nine healthy children. In contrast to the healthy reference group (mu = 4.01 +/- 0.71 microN/m), the mean apparent elastic shear modulus of RBC membrane mu as a parameter of static deformability was significantly increased to 9.05 +/- 1.61 microN/m in children with chronic renal failure measured in the pre-study period. At the 7th week of the correction period of rHuEpo therapy, the haematocrit of treated patients is enhanced to a mean of 0.30 +/- 0.03, whereas mean mu is decreased to 5.41 +/- 0.63 microN/m. Within the maintenance period of rHuEpo treatment (30th week), the parameter mu did not show significant differences to the reference value 3.78 +/- 0.31 microN/m. Additionally, a significant increase in red cell mean corpuscular volume was obtained during rHuEpo therapy. Improved deformability of uraemic RBC induced by the rHuEpo therapy can only be explained by the assumption that in the course of this therapy an increasing number of cells with normalised viscoelastic properties have been formed by stimulated erythropoiesis. PMID- 1857523 TI - Endoscopic management of shoulder pain in long-term haemodialysis patients. AB - In 48 shoulders of 29 patients receiving long-term haemodialysis and complaining of intolerable shoulder pain, endoscopic resection of the coracoacromial ligament was performed under local anaesthesia on an outpatient basis, using the Universal Subcutaneous Endoscope system. Predominant endoscopic findings were proliferation of the subacromial bursae and popping between the coracoacromial ligament and the rotator cuff. Amyloid originating from beta 2 microglobulin (beta 2-M) was demonstrated in 87% of the resected coracoacromial ligaments and 86% of the subacromial bursae. Resection of the coracoacromial ligament relieved the shoulder pain in all patients. PMID- 1857524 TI - Evaluation of peritoneal dialysis solutions with amino acids and glycerol in a rat model. AB - In this study a simple rat model for evaluating the ultrafiltration by peritoneal dialysis solutions is described. Anaesthetised male Sprague-Dawley rats were injected intraperitoneally with dialysis solutions. Zero, 1, 3, or 6 h later, the dialysate volume was determined directly: the abdomen was carefully opened, the intraperitoneal liquid was withdrawn with a syringe and its volume was measured. Good recovery of dialysate, highly reproducible results, and the similarity between the ultrafiltration profiles in rats and published profiles in CAPD patients for control solutions, indicate that the model is valid. The model was then used to evaluate peritoneal dialysis solutions containing a mixture of glycerol and amino acids. Both osmotic agents are chemically compatible and these mixtures provide amino acids and carbohydrates in a single solution. For three mixtures, intraperitoneal dialysate volume were determined as a function of dwell time and the formulation with the desired ultrafiltration could be selected. PMID- 1857525 TI - The effect of cyclosporin administered during a third-party blood transfusion protocol on humoral immune responses. AB - Antigen pre-treatment in animals undoubtedly prolongs graft survival. In man, however, routine pre-transplantation blood transfusions have recently become controversial, principally because of the adverse effect of transfusion-induced sensitisation on graft survival rates. We have monitored the effect of cyclosporin administered during a planned programme of third-party blood transfusions on the development of both cytotoxic and anti-idiotypic antibodies. A total of 24 patients were recruited to the study; ten received cyclosporin with blood transfusions (BT) (group 1), 14 received BT alone (group 2). Anti-HLA antibodies developed in 3 of 9 patients in group 1 and 8 of 12 patients in group 2 (P less than 0.05). Anti-idiotypic antibody activity was detectable in 9 of 9 patients in group 1 and 7 of 12 patients in group 2 (P less than 0.006). The mechanism by which cyclosporin can prevent an anti-HLA antibody response and promote an anti-idiotypic response is unclear. PMID- 1857526 TI - Glomerulocystic kidney disease associated with haemolytic-uraemic syndrome. PMID- 1857527 TI - Spontaneous inflammation-induced remission of parathyroid tumour in secondary hyperparathyroidism. PMID- 1857528 TI - Successful pregnancy of twins in a renal transplant patient with Wegener's granulomatosis. PMID- 1857529 TI - Proteinuria, albumin synthesis and hyperlipidaemia in the nephrotic syndrome. PMID- 1857530 TI - Parathyroid carcinoma in renal failure. PMID- 1857531 TI - Interaction of cyclosporin and ticlopidine. PMID- 1857532 TI - Immediate and long-term prognosis in acute renal failure in the elderly. AB - Acute renal failure (ARF) is particularly frequent in the elderly. A few studies have reviewed immediate prognosis of ARF in older patients, but these do not allow any conclusion on long-term renal prognosis. Our retrospective study included 46 patients over 65 years referred to our renal unit between 1983 and 1989. Survivors were followed up 6-71 months after discharge (mean: 39 months). The evolution of renal function was evaluated by measurement of serum creatinine. Data analysis employed chi 2 with Yates correction, Student t, and Mann-Whitney tests to compare survivors and deceased, and to compare patients with normal and abnormal renal function at follow-up. During hospitalisation 11 patients (24%) died. Our univariate analysis reveals that three variables independently influence mortality: consciousness disturbance (P less than 0.001), high urea concentration (P less than 0.01), and hypoalbuminaemia (P less than 0.001). Age does not adversely affect prognosis. At follow-up 15 patients (43%) had a complete functional recovery, eight (23%) had incomplete renal recovery and two (6%) were on chronic haemodialysis. These results are similar to those observed in a younger population. In conclusion we believe that age alone should not be used to predict the immediate survival or the long-term renal outcome in ARF in the elderly. PMID- 1857533 TI - Haemodialysis: effects on white and red blood cell sodium content and transport. AB - A circulating sodium pump inhibitor, released in response to volume expansion, may, by increasing intracellular sodium concentrations, be responsible for some of the features of the uraemic state. Haemodialysis, by correcting volume overload, would be expected to be associated with a decrease in intracellular sodium towards normal. The effects of a haemodialysis session on leukocyte (WBC) sodium content and transport have not been described and there are conflicting reports of the effects of haemodialysis on erythrocyte (RBC) sodium content and transport. We have measured sodium (NaWBC/RBC) and potassium content (KWBC/RBC), net ouabain-sensitive sodium flux rate (FR) and sodium flux rate constant (RC) before and after a standard haemodialysis session in 20 stable hospital haemodialysis patients. In leukocytes (n = 18), sodium (P = 0.078), FR (P = 0.006), and RC (P = 0.071) decreased over dialysis, whereas in erythrocytes sodium increased (P less than 0.001, n = 19) and RC declined (P = 0.002, n = 18). Although in opposite directions in RBC and WBC, the changes in sodium were toward normal in both cell types. Changes in intracellular sodium content and transport did not correlate with changes in measures of ECF volume or biochemical efficiency of dialysis. We conclude that haemodialysis does affect cell sodium content and transport, but in different ways in different cell types. There was no evidence that haemodialysis removed a sodium pump inhibitor. The use of RBC or WBC as 'model' cells to study sodium transport in uraemia is of questionable validity. PMID- 1857534 TI - Comparison of calcium carbonate and aluminium hydroxide as phosphate binders on biochemical bone markers, PTH(1-84), and bone mineral content in dialysis patients. AB - Bone mineral content, estimated by single-photon absorptiometry of the forearm, serum values of intact parathyroid hormone (PTH(1-84], osteocalcin, alkaline phosphatase, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), and aluminium were determined during treatment with calcium carbonate (CaCO3) or aluminium hydroxide (Al(OH)3) in 11 dialysis patients participating in a randomised cross-over study. Each treatment period lasted 6 months. Serum phosphorus was maintained in the range 1.5-2.0 mmol/l. During Al(OH)3 treatment bone mineral content (BMC) decreased by 11% per half-year (mean), but only by 3% per half-year during CaCO3 treatment (P less than 0.05). Comparing the CaCO3 and Al(OH)3 periods the following differences were found: serum calcium increased during CaCO3 treatment, PTH(1-84) decreased (79% of initial values during CaCO3 versus 196% during Al(OH)3, mean area under curve, P less than 0.05), osteocalcin decreased (89% versus 117%, P less than 0.01), alkaline phosphatase decreased (92% versus 116%, P less than 0.05), and aluminium decreased (56% versus 189%, P less than 0.05). 1,25(OH)2D3 remained unchanged in both periods. No increase in soft-tissue calcification was demonstrated on X-ray of the shoulders in any of the periods. Thus, CaCO3 treatment seems to slow down loss of bone mineral content, and using CaCO3 as phosphate binder may have a more beneficial effect on the progression of uraemic bone disease than Al(OH)3 due to the reduction of hyperparathyroidism and bone turnover. PMID- 1857535 TI - Enhancement of neurite outgrowth from central nervous system neurons in primary culture by thrombin inhibitors. AB - Previous studies have shown that serine protease inhibitors promote neurite outgrowth from neuroblastoma cells, sympathetic neurons and sensory ganglia in culture. In the present study, a neurite promoting activity of thrombin inhibitors such as hirudin, D-Phe,Pro,Arg-CH2Cl, and paraamidinophenylalanine derivatives, was found in rat embryo (E17) septal neurons in primary culture. In contrast, no effect was shown on choline acetyltransferase activity of septal fragments in culture. These results suggest that thrombin inhibitors might interact with a thrombin-like protease involved in the control of neurite outgrowth. PMID- 1857536 TI - The influence of nicotine on local cerebral blood flow in rats. AB - Local cerebral blood flow (LCBF) was measured in conscious rats during an acute nicotine infusion. LCBF was measured using the autoradiographic iodoantipyrine method. LCBF was unchanged in most brain structures during nicotine infusion compared to controls. Significant (P less than 0.05) increases were found in 3 structures (lateral geniculate body, superior colliculus, anteroventral nucleus of the thalamus). These structures have already shown increases in local glucose utilization in a previous study [2]. The observed increases in LCBF are interpreted to be secondary to metabolic activation by nicotine indicating the lack of a direct action of nicotine on cerebral blood vessels. PMID- 1857537 TI - The post-potential excitability modulation of alpha nerve and muscle fibers in human newborn and adult. AB - In order to assess indirectly the excitability of human motor units, the absolute refractory period of the ulnar nerve alpha motor fibers and the absolute irresponsive period of the abductor digiti minimi fibers were measured in 8 premature, 10 fullterm newborns and 10 adults. Results indicate that absolute refractory period of alpha motor nerve fibers appears to be a specific functional property of the membrane, independent of postnatal development. Moreover the maturation of muscle membrane seems slightly delayed in comparison to that of nerve fibers. Indeed the absolute irresponsive period of muscle fibers is slightly higher in premature in comparison with fullterm newborn and adult. PMID- 1857539 TI - Enkephalinergic synaptic axon terminals on serotoninergic neurons in the dorsal raphe nucleus of the rat: an electron microscopic study by the double immunostaining method. AB - Met-enkephalinergic synaptic axon terminals on serotoninergic neurons in the dorsal raphe nucleus of the rat were observed with double immunostaining at the electron microscopic level. Met-enkephalin-like immunoreactive axon terminals were found to make asymmetrical or symmetrical synaptic contacts with serotonin like immunoreactive nerve cell bodies and dendrites. The findings suggest that opioid-containing neurons modulate serotoninergic neurons through synapses in the dorsal raphe nucleus. PMID- 1857538 TI - Direct identification of individual vasopressin-containing nerve terminals of the rat neurohypophysis after 'whole-cell' patch-clamp recordings. AB - The membrane currents in rat neurophypophysial nerve terminals, which contain either vasopressin or oxytocin, have been previously recorded using the 'whole cell' patch-clamp technique. Interpretation of the electrophysiological data would be significantly strengthened by the ability to correlate them with knowledge of the peptide contents of the terminals being studied. Here, a novel method for detection of the peptide hormone, arginine vasopressin, in those individual isolated terminals is described. The unique aspect of this procedure is that the contents of the terminal are aspirated into the recording electrode after 'whole-cell' patch-clamp recording, and then a highly sensitive dot immunobinding assay allows identification of the peptide contents in the terminals. PMID- 1857540 TI - The benzodiazepine triazolam phase-shifts circadian activity rhythms in a diurnal primate, the squirrel monkey (Saimiri sciureus). AB - Triazolam can shift the phase of circadian rhythms in hamsters recorded in constant light or dark. This effect is apparently mediated by physical activity stimulated by the drug. We examined whether triazolam can shift the phase of circadian rhythms in a diurnal primate, the squirrel monkey, that is sedated by triazolam. Single injections of triazolam at 0.15-0.20 mg/kg induced phase advances or delays of monkey activity rhythms recorded in constant light. The phase-response curve is similar to that obtained for hamsters. Behavioral activation is evidently not necessary for a phase-shifting action of triazolam in this primate. A companion study in which triazolam was administered to squirrel monkeys in the dark in a light-dark cycle reentrainment paradigm failed to find evidence for a phase shifting action of triazolam. Shifts induced by triazolam in monkeys recorded in constant light may thus reflect changes in light exposure as a consequence of sedation or altered retinal processing of light. PMID- 1857541 TI - Amyloid beta-protein in cerebral amyloid angiopathy, senile plaques, and preamyloidotic lesions in subcortical arteriosclerotic encephalopathy (Binswanger disease). AB - Cerebral vascular amyloid deposits, senile plaques and neurofibrillary tangles have been found in subcortical arteriosclerotic encephalopathy (Binswanger disease). A mouse antiserum, prepared against a 43-amino acid synthetic peptide homologous to the amyloid beta-protein of Alzheimer disease (anti-SP43), revealed immunoreactive amyloid deposits in meningeal and intracortical blood vessels, senile plaques, intraneuronal amyloid and preamyloid in a neuropathologically confirmed case of Binswanger disease previously reported to have cerebral vascular amyloid deposits. These lesions contained sulfated glycosaminoglycans as determined by the Alcian blue/critical electrolyte concentration method. Similar findings were not observed in a case of Binswanger encephalopathy without cerebral amyloid deposits. Our study indicates that amyloidotic lesions in Binswanger encephalopathy with cerebral amyloid deposits contain amyloid beta protein and sulfated glycosaminoglycans. PMID- 1857542 TI - Grafts of syngenic cultured, adult dorsal root ganglion-derived Schwann cells to the injured spinal cord of adult rats: preliminary morphological studies. AB - Highly enriched cultures of Schwann cells were obtained from adult rat dorsal root ganglia and implanted (5 x 10(5) -9 x 10(5) cells) in the spinal cord of syngenic adult rats at the site of an acute compression lesion produced by a subdural inflatable microballoon. These autografts survived and invaded the host tissue, reducing central cavitation and astrocytic gliosis. They dramatically promoted ingrowth of axons, the majority of which appeared to come from the dorsal roots as judged by their neuropeptide content. Invasion of the transplants by descending, e.g. aminergic fibers, was negligible at survival times of up to 4 months. Nonetheless, autologous Schwann cells, which are readily available in the host, represent a promising material for grafts into the injured spinal cord. PMID- 1857543 TI - PGI2-induced activation and sensitization of articular mechanonociceptors. AB - The effects of PGE2 PGI2 and the stable PGI2 analogue cicaprost on the afferent discharge of ankle joint mechanonociceptors were studied in the anaesthetized rat. Close-arterial injection of PGI2 (0.01-0.1 micrograms) or cicaprost (0.05-5 micrograms) caused both sensitization to mechanical stimulation and excitation of the majority of mechanonociceptors, whereas PGE2 (0.03-3 micrograms) had only weak effects on a small number of nociceptive units. These results suggest the existence of specific PGI2 sensitive receptors (IP receptors) on rat sensory afferent nerves, and support the hypothesis that in the rat endogenous PGI2 plays an important role in the lowering of nociceptive thresholds in inflamed joints. PMID- 1857544 TI - A premovement silent period does not occur prior to rapid changes of velocity during human limb movements. AB - Surface electromyographic activity (EMG) of the interosseous dorsalis I, the hand extensors and the biceps muscles was analysed in human young normal subjects for the occurrence of a precontraction (PCSP) or a premovement silent period (PMSP) before a sudden increase in tension or rapid change of position after a small isometric contraction or slow isotonic movement. Contrary to the results of Conrad et al. (Exp. Brain Res., 51 (1983) 310-313), in whose experiments the contraction condition changed from isometric to isotonic, a PCSP or PMSP could never be observed in our experiments, where contractions or movements first started at a low force level or with a low speed which had to be changed most rapidly after 2 s and where the recording condition remained strictly either isometric or isotonic. It is concluded that the central nervous system resets the motoneuronal pool activity when the central program is changed from the control of an isometric to the control of an isotonic contraction. PMID- 1857545 TI - Neuronal activity in frontal speech area 44 of the human cerebral cortex during word recognition. AB - The activity of neurons was recorded from cortical speech area 44 of human patients with diagnostic and/or therapeutical depth electrodes while they were performing word recognition and object naming tasks. Some cells responded selectively to either semantic or phonological aspects of word processing with the same latency, others responded consecutively to both semantic and phonological features. The present finding provides the first demonstration of neuronal mechanisms in frontal language cortex and evidences that both consecutive and parallel processing of these speech signs occur in neuronal activity of this area. PMID- 1857546 TI - Hyperpolarizing inward rectification in rat neocortical neurons located in the superficial layers. AB - Intracellular recordings were performed in neurons located in layers II/III of rat neocortical slices maintained in vitro. High intensity negative current pulses elicited hyperpolarizing responses that were characterized by a sag of membrane potential towards the resting level. Graphically, this inward rectification was reflected as a break in the slope of the I-V plot at membrane level of around -98 mV. The inward rectification was only partially reduced by the bath perfusion of Cs+ (3 mM). In contrast, it was abolished by the extracellular addition of Ba2+ (3 mM) or the intracellular injection of QX-314 (50 mM). Our findings indicate that Ba2+ and QX-314 are more effective than Cs+ in blocking the hyperpolarizing inward rectification generated by rat neocortical cells located in the superficial layers. PMID- 1857547 TI - Functional mapping of the rat brain during vocalizations: a 2-deoxyglucose study. AB - Autoradiographic [14C]2-deoxyglucose (2-DG) procedures were used to map the functional activity in the CNS during vocalizations elicited by electrical stimulation of the midbrain reticular formation (MRF) in behaving rats. Following injection of 2-DG, rats received MRF stimulation through stainless steel electrodes over 90 min. Yoked controls received 2-DG injection followed by playback of the recorded vocalizations. Relative differences in peak isotope uptake (gray/white matter ratios) in 22 structures related to vocalization were compared between the two groups. The major findings were localized to hypothalamus, midbrain and brainstem structures. Significant increases in 2-DG uptake were noted in the following structures in MRF stimulated rats: dorsolateral central gray (PAG), MRF, lateral hypothalamus (LH), ventromedial hypothalamus (VmH), paraventricular nucleus (PVN) and nucleus ambiguus (NA). Cortical structures were not activated during MRF stimulation. The PAG and NA are known to be important relays in the production of vocalizations. MRF stimulation, therefore, activates the motor output pathways for vocalization, but does not appear to activate cortical and limbic motivational centers. PMID- 1857548 TI - Hypertonic media produce Ca(2+)-dependent release of calcitonin gene-related peptide from capsaicin-sensitive nerve fibres in the rat urinary bladder. AB - Superfusion of slices of the rat urinary bladder with hypertonic NaCl produced a remarkable and concentration-dependent (150-280 mM) increase in the outflow of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI). This effect was completely abolished by pre-exposure of the tissue to capsaicin (10 microM for 20 min) or by superfusion with a Ca(2+)-free medium. Capsaicin (10 microM) was still able to release a consistent amount of CGRP-LI from tissue pre-exposed (20 min) to 280 mM NaCl. Similarly, hypertonic sucrose (160 mM added to the physiological salt solution) induced a consistent release of CGRP-LI that was abolished by capsaicin-pretreatment or in a Ca(2+)-free medium. The experiments demonstrate that hypertonic solutions activate the efferent function of capsaicin-sensitive neurons and suggest that this event may have some relevance in pathophysiological conditions of the lower urinary tract in which hypertonic urine may diffuse to submucosal layers. PMID- 1857549 TI - Dystrophin in central nervous system: a developmental, regional distribution and subcellular localization study. AB - Dystrophin, the protein encoded by the Duchenne muscular dystrophy gene has been shown to be expressed in central nervous system. In the present study, polyclonal antibodies raised against 3 fusion proteins constructed from different structural domains of dystrophin were used to identify dystrophin in protein extracts from rat and mdx mouse brain. The developmental expression of the protein, its regional distribution in rat brain and its localization in rat brain subcellular fractions were also examined. We found that dystrophin or a 'dystrophin-related protein' is expressed in mdx mouse brain. Dystrophin is detectable at very early stages of rat brain development and is expressed in all adult brain regions examined, although quantitative regional differences were found. Subcellular distribution analysis indicates that dystrophin is absent in mitochondrial and synaptic vesicle-enriched fractions but is recovered in the synaptic plasma membrane fraction. PMID- 1857550 TI - Marked variations of the relative distributions of neurotensin and neuromedin N in micropunched rat brain areas suggest differential processing of their common precursor. AB - Neuromedin N (NN) is a hexapeptide that shares a four amino acid identity with the C-terminus of neurotensin (NT) and exhibits NT-like effects in the central nervous system. Both peptides were recently shown to be encoded in the same precursor molecule. By means of specific and sensitive radioimmunoassays, we compared the distribution of immunoreactive NT and NN (iNT and iNN) in micropunched rat brain structures. The data revealed marked regional variations in the ratio of iNT over iNN. For instance, the ratio value was 4.5 in the posterior hypothalamus and 0.8 in the mammillary bodies. Reverse phase HPLC analysis of extracts of several brain regions showed that iNT and iNN coeluted with synthetic NT and NN, respectively. The results suggest that differential processing of the common neurotensin/neuromedin N precursor occurs in various regions of the rat brain. PMID- 1857551 TI - Increased cell number in remaining cerebellar nuclei after cerebellar hemispherectomy in neonatal rats. AB - After cerebellar hemispherectomy before the 10th day of life aberrant cerebello rubral projections develop from the nuclei in the remaining hemisphere, which terminate on the ipsilateral side. These aberrant fibres stem from separate parent cells in the lateral and interposed nuclei. The problem addressed by the present study was whether the number of neurones in these nuclei is increased after early cerebellar hemispherectomy. Results demonstrate that the number of neurones was increased by 50-60%. The volumes of the nuclei were also increased (14-31%) but much less so, which indicates a relative decrease in neuropil per neuron. PMID- 1857552 TI - Diabetes mellitus-associated decrease in nerve growth factor levels is reversed by allogeneic pancreatic islet transplantation. AB - After an untreated 5-month duration of streptozotocin (STZ)-induced diabetes mellitus (DM), nerve growth factor (NGF) levels in BDE rats were decreased to 45 65% of control in the sympathetically innervated target organs iris and submandibular gland, in the superior cervical ganglion (containing NGF-dependent sympathetic perikarya projecting to the cranial targets), and in the NGF transporting sciatic nerve. Successful allogeneic pancreatic islet transplantation (providing a physiological glucose homeostasis without immunosuppression) after 3-4 weeks of DM reversed the DM-related decrease in NGF levels 4 months after transplantation as compared with untreated diabetic rats. By contrast, NGF levels in the treated vas deferens (innervated by short postganglionic sympathetic neurons) remained increased as in the untreated diabetic rats (175% of control). Thus, DM-associated changes in endogenous NGF levels seem to be reversible by institution of metabolic control, at least at an early stage of DM when NGF-responsive neurons have not been deprived of NGF for a long time. PMID- 1857553 TI - Intrathalamic injections of gamma-hydroxybutyric acid increase genetic absence seizures in rats. AB - The effects of intrathalamic injections of gamma-hydroxybutyric acid (GHB) and of NCS 382 85, a specific antagonist of GHB receptors, were evaluated in rats with spontaneous generalized absence epilepsy. Bilateral injections of GHB (25 and 50 micrograms/side) into the mediolateral thalamus increased spontaneous spike and wave discharges (SWD) in a dose-dependent fashion. This effect was suppressed by administration of NCS 382 85 (50 micrograms/side). Bilateral injection of NCS 382 85 alone (50 and 100 micrograms/side) into the same sites had no effect on SWD duration. Injection of GHB or NCS 382 85 into the midline thalamus and the area of reticular nuclei did not modify the SWD. These data suggest that GHB receptors in the mediolateral thalamus may be involved in the control of spontaneous SWD in this rat model of petit mal epilepsy. PMID- 1857554 TI - Intrastriatal dialysis evidence for a direct inhibitory effect of benztropine on dopamine re-uptake. AB - A direct inhibitory effect of benztropine on dopamine (DA) reuptake in the striatum was established by in vivo microdialysis of anesthetized rats. Benztropine was infused by means of a microdialysis probe positioned stereotaxically in the striatum. Extracellular DA collected from dialysate was measured by high-performance liquid chromatography using an electrochemical detector. Benztropine was found to cause a dose-dependent inhibition of re-uptake of DA in the nerve terminal area of the dopaminergic system. PMID- 1857555 TI - Expression of two forms of human dopamine-beta-hydroxylase in COS cells. AB - We previously reported four different cDNA clones encoding human dopamine-beta hydroxylase (Kobayashi et al., Nucl. Acids Res., 17 (1989) 1089-1102). These clones were different in a 3' untranslated region (types A and B) and/or in 6 nucleotides in mRNAs. The difference at nucleotide 910 caused an amino acid change between Ala (A) and Ser (S) at amino acid residue 304 (DBH/A and DBH/S). We succeeded in expressing both of DBH/A and DBH/S of type A cDNAs in COS cell. Both of the expressed proteins showed enzyme activities and immunoreactivities. The two proteins had similar kinetic constants, but had different homospecific activities (activities per enzyme protein); the homospecific activity of human DBH/S was low, approximately one thirteenth that of human DBH/A. PMID- 1857556 TI - Central administration of interferon-alpha enhances rat sympathetic nerve activity to the spleen. AB - Intracerebroventricular injection of recombinant human interferon-alpha (IFN alpha) in a dose of 1 x 10(4) U, but not 3 x 10(3) U, produced a long-lasting (at least for 60 min) increase (2.5-5 times the preinjection level) in the electrical activity of splenic sympathetic nerve filaments in urethane-alpha chloralose anesthetized rats. Intravenous injection of IFN-alpha (3 x 10(4) U) also produced a similar excitation of splenic sympathetic nerves. There were no changes in arterial blood pressure and body temperature. The result, together with the previous findings, provides further evidence that the central IFN-alpha-induced suppression of cytotoxic activity of splenic natural killer cells may be mediated by the sympathetic innervation. PMID- 1857557 TI - Cortical post-spike facilitations in elbow muscles during isometric contraction. AB - Averaged responses of elbow muscles to action potentials of 37 single motor cortex cells were analyzed in two Macaca fascicularis monkeys during performance of a submaximal but high level isometric contraction. Post-spike facilitations (PSFs) of the rectified electromyographic activity (EMG) were frequently (72%) observed. They consisted of PSFs largely distributed in agonistic (biceps brachii and brachioradialis) and antagonistic (triceps brachii) muscles. Some post-spike inhibitions (7%) were also noted. As compared with distal muscles PSFs, most of the proximal PSFs were of lower amplitude, probably because of the higher level of the contractions. These PSFs were also of longer latency. The data indicate functional connectivity between motor cortical cells and proximal limb muscles. Cortical cells with oligosynaptic and even, for a few of them, with monosynaptic connections to the alpha-motoneurones may contribute to recruitment of motor units (MUs) involved in proximal limb muscle contraction. PMID- 1857558 TI - Autoradiographic localization of binding sites for second messengers on neurones and astrocytes of cultured rat cerebellum. AB - Using autoradiographic techniques, studies on the cellular localization of binding sites for second messengers in explant cultures of rat cerebellum have been performed. Binding of [3H]inositoltrisphosphate ([3H]IP3), [3H]phorbol dibutyrate ([3H]PDBu) occurred to Purkinje cells whereas binding sites for [3H]forskolin were mainly confined to granule cells and outgrowing nerve fibres. A great number of astrocytes was also labelled by all three radio-ligands. Binding of [3H]IP3, [3H]PDBu and [3H]forskolin was displaced by unlabelled compounds, suggesting specific binding. Our observations provide strong evidence that in addition to neurones, astrocytes also express binding sites for second messengers. PMID- 1857559 TI - Interaction of Ca-channel blockers and high pressure at the crustacean neuromuscular junction. AB - Exposure to high pressure causes a significant depression of synaptic transmission. We examined the effects of various Ca-channel blockers and their interaction with high pressure on excitatory neuromuscular junction currents (EJCs) of lobster abdominal muscles. Reduced [Ca2+]o to half of normal concentration or exposure to 40-60 microM CdCl2, 10-20 microM NiCl2 and 1 microM omega-conotoxin decreased EJCs by 50%. Nifedipine, Nitrendipine and Bay K-8644 were ineffective. Either Ca-blockers or reduced [Ca2+]o, enhanced EJC suppression exerted by high pressure. The data suggest that high pressure primarily affects Ca2+ inflow at the presynaptic terminals through N-type voltage-gated Ca-channel. PMID- 1857560 TI - Augmentation of rat brain endogenous monoamine oxidase inhibitory activity (tribulin) by electroconvulsive shock. AB - The effects of acute and subacute supramaximal and submaximal electroshock induced convulsions on rat brain tribulin activity were investigated. Both supramaximal and submaximal shocks induced a marked increase, as measured 30 min after the onset of convulsions, with a significantly greater effect from the former. The effects were no longer present 24 h after stimulus. Repeated electroshock for 5 and 10 days showed that submaximal stimuli produced little change, whereas supramaximal shock brought about a significant increase in tribulin activity, the effect being greater with 10-day exposure. The results are not inconsistent with the clinical observation that a single electroconvulsive therapy (ECT) shock has little clinical usefulness but that repeated shocks, spread over several days, result in therapeutic benefit due, perhaps, to an increase in brain concentrations of tribulin, an endogenous monoamine oxidase inhibitor. PMID- 1857561 TI - Retinal fibers make synaptic contact with neuropeptide Y and enkephalin immunoreactive neurons in the intergeniculate leaflet of the rat. AB - Direct synapses between retinal fibers and neuropeptide Y (NPY) and/or enkephalin immunoreactive (ENK-I) neurons were investigated in the intergeniculate leaflet (IGL) of the rat, using combined immunohistochemical and degeneration techniques. Degenerating retinal fibers terminated on dendrites of NPY-I and/or ENK-I neurons. NPY-I fibers in the IGL formed axo-dendritic synapses on non immunoreactive dendrites. Most of them were asymmetrical synapses. ENK-I axon terminals contacted non-immunoreactive dendrites with symmetrical synapse. PMID- 1857562 TI - Regulation of calcitonin gene-related peptide mRNA expression in the hearts of spontaneously hypertensive rats by testosterone. AB - Previous studies have demonstrated the existence of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibres and nerve cell bodies in the rat heart. Using polymerase chain reaction we have investigated whether CGRP messenger RNA (mRNA) could be detected in heart tissue of spontaneously hypertensive rats, and whether CGRP-mRNA levels are affected by gonadectomy and testosterone substitution. Two weeks after castration CGRP-mRNA levels decreased to 65.2 +/- 6.4% of control values, whereas daily dihydrotestosterone substitution reversed this effect (88.0 +/- 1.2% of control). Our results indicate that steroid hormones control the expression of intracardiac CGRP on a pretranslational level. PMID- 1857564 TI - Nephrology in the inner city. PMID- 1857563 TI - Reversal of 'handedness' in rats is achieved more effectively by training under peripheral than under central blockade of the preferred forepaw. AB - Reversal of forepaw preference was studied in rats under conditions of peripheral (bracelet) or central (inactivation of contralateral motor cortex and caudate nucleus by intracerebral injection of tetrodotoxin) preferred limb block. Persisting change of the forepaw preferred when reaching for food into a tubular feeder was achieved on the average after 91 (n = 27) and 211 (n = 26) reaches, respectively. When tested in another task (recovering food pellets from a horizontal shelf accessible through a narrow slit below the ceiling of the test box) same rats displayed identical (45%) and opposite (15%) preference or were ambidextrous (40%). Forced change of handedness on the tubular feeder task was accompanied by similar change of preference on the shelf task in only 17% rats. It is concluded that rather independent lateralisation of the two tasks reflects differential contribution of the corticospinal, rubrospinal and ventromedial motor systems. Reversal training proceeds faster with peripheral blockade which establishes not only the new preference but also inhibits the original one. PMID- 1857565 TI - Nephrology in the inner city. PMID- 1857566 TI - The health of poor and minority people in the inner city. PMID- 1857567 TI - Imaging techniques and asymptomatic renal cell carcinomas. PMID- 1857568 TI - Trends in kidney procurement and transplantation in New York State. AB - The growth in the number of Medicare patients with end stage renal disease (ESRD) in New York State receiving cadaver kidney transplants in the 1980s substantially lagged behind growth in the nation. Compared to the United States, New Yorkers on dialysis had less access to transplants. The greatest decline in transplant rates was experienced by New York's black population. During the early and mid-1980s, considerable transplant rate growth in New York City was maintained, despite very slow growth in local kidney procurement, by importing kidneys from other states, by residents seeking transplants elsewhere, and by a greater proportion of transplants going to Medicare ESRD patients. Since 1986, the number of kidneys procured in New York City increased while the number procured nationally fell. However, kidney imports to New York City dropped dramatically and thus the number of cadaver transplants declined despite the growth in local procurement. Upstate, procurement and transplants started at a higher level, but grew even more slowly. PMID- 1857569 TI - Effective hypertension control in inner city blacks. AB - A clinic for patients with "resistant" hypertension was established and patients were followed by one physician, nurse, and secretary. The records of 105 randomly chosen patients out of 700 were reviewed. In 86 of 105 (82%), diastolic blood pressure was controlled (less than 90 mm Hg) (group I), but in 19 patients, after 54 +/- 6 (mean +/- standard error) months, it remained greater than 90 mm Hg (group II) with substantial improvement in 53% (10 of 19 patients). The two groups were similar in age (57 +/- 1 vs 54 +/- 3 years), race (84% vs 74% blacks), and sex (75% vs 86% female). The entry blood pressures in groups I and II were similar, 170 +/- 3/101 +/- 1 and 167 +/- 6/105 +/- 3 mm Hg, respectively. Last visit blood pressure was 130 +/- 1/79 +/- 1 in group I, lower than 156 +/- 5/94 +/- 2 in group II (p less than 0.05). At entry into the clinic and at the last visit, dosing and type of medications were similar in both groups. Although patient visits averaged 6.7/yr in both groups, patients in group II missed 1.7 +/ 0.3 compared with 0.9 +/- 0.1 visits/year for group I (p less than 0.01). Group II patients were also less compliant with medications, primarily because of psychosocial problems. Medications, however, were more available to this group, since 16 of 19 (84%) were Medicaid recipients, compared with 46 of 86 (53%) in group I (p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1857570 TI - Lipid abnormalities in black renal patients. AB - Racial differences in lipoprotein (LP) and cardiovascular (CV) abnormalities have been noted in the general population and in the population of patients on dialysis. Few studies have investigated the interaction of race and LP and CV disturbances in other renal disease groups. We studied lipid profiles and risk ratios (total cholesterol (TC)/high density lipoprotein-cholesterol) (HDL-C) and apolipoprotein (apo) A-I/apo B (A-I/B)) and the influence of race across a spectrum of renal disease groups (normal renal function (NRD), nephrotic range proteinuria (NS), hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), post-transplant (TR), renal insufficiency (RI)). We also performed a longitudinal study of lipid profiles in patients with end stage renal disease (ESRD) and the relationship of these profiles to race and other variables. There was a general tendency towards a better CV risk profile for blacks than whites in all the groups. Blacks tended to have lower TC, higher HDL-C, lower TC/HDL-C, higher apo A-I, lower apo B, and higher A-I/B. We analyzed four yearly cross sections of the HD and CAPD populations using ANOVA with adjustment for appropriate covariates. Whites had lower HDL-C and a higher TC/HDL-C risk ratio than blacks. HD patients had lower TC, TC/HDL-C, apo A-I, and apo B than CAPD patients, and women had higher TC than men. When lipid profiles were studied longitudinally by yearly intervals, no consistent significant changes were seen, but over two years, levels of apo B fell and A-I/B rose. Race had no significant effect on any of the longitudinal data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1857571 TI - A retrospective analysis of the metabolic status of stone formers in the New York City metropolitan areas. AB - Eighty stone-forming patients were evaluated as outpatients for risk factors involved in stone formation. Analyses of the major stone risk parameters in the 24-hour collections indicated low volume (less than 2L) in about 79% of these patients. Forty percent of all patients were found to be hypocitraturic, 30% were hyperoxaluric, 18% were hypercalciuric, and 13% were hyperuricosuric. Sixty-one percent of the patients had a normal calcium load study; of these, four patients were uric acid stone formers. The remaining 39% of patients were classified as either absorptive hypercalciuric (16 patients), or fasting hypercalciuric with normal (12 patients) or elevated (3 patients) serum parathyroid hormone (PTH) levels. Of these 31 patients, 61% were not hypercalciuric on the basis of the 24 hour urine collections. The protocol provided a diagnosis in over 98% of patients. Low urinary volume was the only defect found in 5% of patients, while more than one risk factor was identified in 93%. PMID- 1857572 TI - Identification of asymptomatic renal cell carcinomas utilizing modern radiographic techniques. AB - The more liberal use of ultrasonography and computed tomography has made more common the incidental discovery of renal masses. The charts of 105 patients surgically treated for renal cell carcinoma at a teaching hospital from 1983 to 1987 were reviewed. The incidence of incidentally found asymptomatic tumors was 47% (49/105 patients). Of the incidentally found tumors, 55% were stage I and only 14% were stage III; for symptomatic patients, 39% of tumors were stage I and 27% were stage III. This study also found that the classical triad of pain, hematuria, and flank mass was present in only 3.8% (4/105) of patients. Tumors found incidentally will usually be of lower pathologic stage and may carry a better prognosis. PMID- 1857573 TI - Diabetic nephropathy in the inner city. PMID- 1857574 TI - Human immunodeficiency virus/acquired immunodeficiency syndrome nephropathy in the inner city. PMID- 1857575 TI - Poverty, ethnicity, and dialysis services in Israel. PMID- 1857576 TI - Pulmonary-renal syndrome. Its clinicopathologic approach in 1991. PMID- 1857577 TI - Administrative challenges in delivering inner city renal care. PMID- 1857578 TI - Scintigraphy in sports injuries: is it underutilized? PMID- 1857579 TI - Imaging of Pneumocystis carinii pneumonia with 111In-labelled non-specific polyclonal IgG: an experimental study in rats. AB - The relative sensitivity of imaging with 67Ga-citrate (67Ga) and non-specific human polyclonal IgG radiolabelled with 111In (111In-IgG) for the detection of Pneumocystis carinii pneumonia (PCP) was determined in rats. Pneumocystis carinii pneumonia was induced by low protein diet and dexamethasone. The course of the disease was monitored by serial imaging with 111In-IgG and 67Ga. Diffuse accumulation of both radiopharmaceuticals was observed in the lungs of infected animals (infection was verified by histological examination of the lungs), however, accumulation of 111In-IgG was consistently higher. In rats with early PCP, 111In-IgG imaging revealed pulmonary accumulation in animals with normal chest radiographs and 67Ga scans. In animals successfully treated for PCP, decreased pulmonary accumulation of 111In-IgG coincided with histological improvements. Several animals developed superinfection with bacteria or fungi. These animals had striking focal accumulation of 111In-IgG, in addition to the pattern of generalized uptake. Gallium concentration in these animals did not show this focal accumulation. These observations suggest that 111In-IgG may be useful for detecting PCP and pulmonary abscesses in the immunocompromised host. PMID- 1857580 TI - Choice of parameter for expressing bone mineralization. AB - In this cross-sectional study, the relative importance of anthropometric factors and that of biological parameters on bone mineralization were evaluated and their practical implications inferred on the choice of the parameter to be used for the estimation of bone mineralization. A close relationship between anthropometric factors and bone mineral content (BMC) was observed and this relationship was shown to be independent of age. Furthermore, by regression analyses, anthropometric parameters appeared to explain a large part of the variance in BMC and preceded the hormonal parameters in the stepwise analysis of this model. Using bone mineral density (BMD) data, however, we observed a weaker relationship between anthropometric factors and bone mineralization and a relatively stronger relationship between steroid hormones and bone mineralization than those observed using the BMC data. Furthermore, by multiple regression analysis the hormonal factors preceded the anthropometric parameters in the stepwise analysis of the model. As strong epidemiological and clinical evidence exists on the relationship between steroid hormones and bone loss, these results constitute a supplementary argument for the use of BMD for the estimation of bone mineralization. PMID- 1857581 TI - Ultrasound and HIDA: scanning in evaluating bile leaks after cholecystectomy. AB - Ultrasound and 99Tcm-HIDA scanning were compared in the evaluation of postoperative biliary leakage after cholecystectomy. In thirty-five patients the abdomen was scanned and imaged on the first postoperative day. Isotope activity in the right upper quadrant and whole abdomen was determined to obtain an activity ratio. Ultrasonography was also performed. Accumulation of 99Tcm-HIDA in the gall bladder bed or over the surface of the liver was regarded as evidence of a bile leak. Eleven patients had abnormal 99Tcm-HIDA images (activity ratios of 0.20-0.77, mean 0.51) but only five patients had loculated fluid on ultrasound scanning. Twenty-four patients had normal 99Tcm-HIDA images (activity ratios of 0 0.17, mean 0.21), but fifteen of these had loculated fluid on ultrasound scanning. We conclude that bile leaks occur in 30% of patients following cholecystectomy and are best detected by 99Tcm scanning rather than ultrasonography. PMID- 1857583 TI - Monoclonal antibody pretargetting techniques for tumour localization: the avidin biotin system. International Workshop on Techniques for Amplification of Tumour Targetting. PMID- 1857582 TI - Radionuclide imaging clinical study. Corporeal 133Xe washout for detecting venous leakage in impotence. AB - A quantitative test, corporeal 133Xe washout, was developed to detect venogenic impotence. Data were acquired in frame mode after intracorporeal injection of 0.1 ml (1-2 mCi or 37-74 MBq) of 133Xe in saline on one side of the midline just behind the glans in the flaccid state for 20 min. A time-activity curve (TAC) was generated from the region of interest (ROI) at the site of injection and a computer routine was then used to calculate clearance half-time (T1/2) in minutes and flow rate (Q) in ml/100 g tissue/min from corporeal 133Xe clearance. The data from 12 controls and 21 patients with venous leakage were analysed. In patients with venogenic impotence, T1/2 (mean +/- S.D.) was greatly increased (24.4 +/- 10.7 min vs 10.7 +/- 4.6 min in controls, P less than 0.005) whereas Q markedly decreased (2.4 +/- 1.3 ml/100 g tissue/min vs 5.4 +/- 2.3 ml/100 g tissue/min in controls, P less than 0.005). The sensitivity and specificity for detecting venous leakage at the optimal threshold of T1/2 equal to 13 min and Q equal to 3.7 ml/100 g tissue/min were 95 and 75%, respectively. The corporeal 133Xe clearance half-time and flow rate are two simple and clinically useful indices for detecting venous leakage. PMID- 1857584 TI - Measurement of hepatic blood flow by use of per-rectal portal scintigraphy with 133Xe. AB - A relatively noninvasive method is needed to evaluate the hepatic blood flow of patients with liver disease. We used per-rectal portal scintigraphy with 133Xe, and analysed the time-activity curves of the liver and portal vein. To do this, wash-out curves of the liver were plotted, and the hepatic blood flow and the ratio of the blood flow to the right lobe of the liver to that to the left lobe (R/L ratio) were calculated. The mean hepatic blood flow was 137 +/- 23 ml/100 g/min for four patients with fatty liver, 139 +/- 16 ml/100 g/min for seven patients with chronic persistent hepatitis, 120 +/- 15 ml/100 g/min for ten patients with chronic aggressive hepatitis, and 75 +/- 21 ml/100 g/min for 14 patients with cirrhosis. All seven patients with hepatic blood flow that was less than 100 ml/100 g/min and an R/L ratio less than 1.0 had cirrhosis. Only two of the 22 patients with hepatic blood flow that was greater than 100 ml/100 g/min and an R/L ratio greater than 1.0 had cirrhosis. Per-rectal portal scintigraphy can be used to measure the hepatic blood flow, but it was not useful for the diagnosis of fatty liver. PMID- 1857585 TI - Purification of radioiodinated monoclonal antibodies using a simple 'closed procedure' device. AB - An elution device has been constructed which is capable of drawing radiolabelled monoclonal antibody through a Sephadex-G chromatography column under negative pressure. Monoclonal antibodies against ovarian carcinoma and T and B lymphocytes were radioiodinated using the Chloramine-T method. Labelling efficiencies were in the range 75-85%. After passing through the chromatographic eluter no 'free' iodide was detected in the antibody samples. The apparatus was simple to use and safe to the operator. PMID- 1857586 TI - [The space-time distribution of the mRNA of the nuclear proteins c-myc and P-53 in the development of the clawed toad studied by hybridization in situ]. AB - We studied distribution of mRNA for nuclear protooncogene c-myc and nuclear protein P-53 in mature oocytes and embryos of Xenopus laevis from the stage of fertilization up to the stage of hatching by in situ hybridization with histological sections. mRNA for c-myc was present in all cells of the embryo at all studied developmental stages. Between the stage of fertilization and up to the late blastula, mRNA concentration for c-myc decreased progressively in all embryonic cells. During gastrulation a local increase in the concentration of this messenger was found in dorsal mesoderm and ectoderm. At the stage of neurula increased concentration of mRNA for c-myc was observed in all cells of the embryo but the hybridization signal increased particularly distinctly in cells of the neural tube. In studies of P-53 mRNA distribution hybridization signal was detected only in brain cells after stage 20 of development (after closure of the neural folds) and up to the stage of hatching. PMID- 1857587 TI - [The biochemical aspects of pineal gland functioning in the rat in ontogeny]. AB - We have studied metabolic pathways of serotonin in epiphysis of Wistar male rats at the age of 1; 1,5; 2; 3; 6; 12; 24 and 36 months. Epiphysis retains its functional activity throughout the life, however, serotonin metabolism in epiphysis undergoes marked changes. The main regulatory principle is the switch of serotonin metabolic pathways in the pineal gland. Most distinct changes between hydroxy- and methoxyindols in epiphysis have been observed during the periods of age-associated hormonal rearrangements like sexual maturation or involution of the gonad function at the old age. PMID- 1857588 TI - [The embryotoxic effects of monohydric alcohols]. AB - We have compared the embryotoxic effect of aliphatic alcohols on antenatal embryogenesis of rats and the activity of alcohol dehydrogenase (EC.1.1.1.1) in embryonic hepatocytes. The embryotoxic activity of the used alcohols in equitoxic doses (assessed as the lethal effect) showed some dependence on their chemical structure. Earlier it has been demonstrated that there is a similar dependence for the mutagenic effects of the alcohols at the chromosomal level. All tested compounds, with the exception of decanol, distinctly retarded the development, but did not exert any teratogenic action. The administration of aliphatic alcohols also led to a significant decrease in the activity of alcohol dehydrogenase in fetal hepatocytes. PMID- 1857589 TI - [The bone marrow origin of the cells encapsulating a foreign body in the peritoneal cavity of xenogeneic radiation chimeras]. AB - The origin and ultrastructure of the cells, encapsulating foreign body in peritoneal cavity of xenogeneic (rat in mouse) radiation chimeras was studied. The donor nature of the cells was identified by their karyotype and by DNA hybridization with rat ID-element. Cells with ultrastructural characteristics of fibroblasts encapsulating foreign body in the peritoneal cavity of the xenogeneic radiation chimeras were shown to originate from the transplanted (donor) bone marrow. PMID- 1857590 TI - [The dynamics of embryonic mortality in inbred Drosophila strains]. AB - This paper describes embryonic mortality in selected inbred strains of Drosophila studied over time. We found that the incidence rate of nondeveloping eggs increases up to 100% during the first 4 days after oviposition in the strain selected for high embryonic mortality (HEM). We have analyzed the contribution of both sexes to the realization of this effect and possible mechanisms of its appearance. PMID- 1857591 TI - [Tissue systems with stem cells]. AB - This paper presents a short historical review of scientific concepts and experimental approaches to analysis of stem cells in various tissue systems. Main problems and perspectives of investigation in this field are discussed. PMID- 1857593 TI - [Hematopoietic stem cells in mice during embryonic development preceding the establishment of liver hematopoiesis]. AB - We studied the time course of appearance of CFUs (7-8 days old) in embryos of (C57B1/6 x CBA)F1 mice from the 8th day of embryonic development. Significant amounts of CFUs could be detected from the 10th day of development, initially in the body of the embryo from the stage of 30-33 pairs of somites, then in the yolk sac and still later, from the stage of about 40 pairs of somites, in liver anlage. CFUs could not be reliably detected until the 9th day of development either in the embryo itself or in the yolk sac. However, after incubation of nine day old embryos for four days in organ culture, such cultures contained CFUs. CFUs could be found in significant levels in embryos explanted from the embryos at the stage no earlier than 24 pairs of somites. When the yolk sac and the embryo were cultivated separately, CFUs could also be detected, however, the removal of liver primordium from the embryo did not influence the amount of CFUs in its body. CFUs were not found in cultures of liver primordium from nine day old embryos. Thus, we can detect pre-CFUs in 9 day old embryos at the stage 25-28 pairs of somites using the system of organ culture; at the same time CFUs cannot be found in intact embryos of the same age. These data provide evidence that before the establishment of liver hemopoiesis precursors of CFUs are located both in the yolk sac and in the embryo outside rudimentary liver. However, our results do not provide any data for the conclusion about the primary source of pre-CFUs in the mouse embryo. PMID- 1857592 TI - [The precursor hematopoietic cell: its origin in ontogeny, proliferative activity and proliferative potential]. AB - Cells responsible for repopulation of irradiated longterm cultures of murine bone marrow and capable of generating CFUs for at least 4-5 weeks after seeding referred here to as primitive hemopoietic stem cells (P-HSC) were assayed by limiting dilution analysis. During development of mice P-HSC can be detected for the first time in the liver of 12-13-day-old embryos and their number is about 10 per organ. At day 17-18 of gestation the number of P-HSC increases ten-fold; however, we could not detect the proliferation of these cells using the technique of hydroxyurea suicide. In the adult mouse P-HSC content is about 100 precursors per femur and their concentration is one P-HSC per 1-2 x 10(5) bone marrow cells. P-HSC content in the spleen is 0.5 per 10(6) cells. In vivo treatment with 5 fluorouracil or hydroxyurea (six injections every 6 h) does not alter significantly the number of P-HSC, although either treatment kills about 99% of CFUs. Several months after reconstitution of lethally irradiated mice with a "small" inoculum of bone marrow cells (0.20-0.35 x 10(6)) the number of bone marrow P-HSC was reduced as compared to that in animals reconstituted by injection of a "large" cell dose (20-35 x 10(6)). These data suggest that P-HSC have limited proliferative potential and are incapable of self-maintenance. PMID- 1857594 TI - [The characteristics of the hematopoietic cells forming colonies on cellulose acetate membranes and their distinctions from other clonogenic cells]. AB - In order to characterize hemopoietic cells forming colonies on membranes of cellulose acetate (CFU-acm) implanted into the peritoneal cavity of mice, we studied the effect of factors stimulating and inhibiting granulocytopoiesis on these cells. Proliferation of CFU-acm can be controlled by humoral factors and this allows us to conclude that they are not identical to CFUs and probably belong to the compartment of early hemopoietic cells of the granulocyte series. We also present evidence for fractional composition, ultrastructure and bone marrow origin of cells belonging to the layer providing for hemopoietic microenvironment for the resulting foci of hemopoiesis; we also present evidence for the role of fibroblasts (fibroblast-like cells) in the maintenance of hemopoiesis. Experiments on transplantation of bone marrow from several rodent species to syn-, allo- and xenogenic recipients allowed us to study interactions of hemopoietic elements of colonies with cells of the underlying layer. PMID- 1857595 TI - [The regulation of hematopoietic stem cell proliferation and differentiation (CFU S) during antigenic exposure]. AB - Hemopoietic stem cell (CFUs) proliferation is controlled by regulatory activities (stimulator and inhibitor) produced by bone marrow macrophages. Previously it has been shown that antigen administration stimulates CFUs proliferation. The data obtained in this study show the possible mechanism of antigen-induced stimulation of CFUs proliferation. 3-4 days after antigen injection bone marrow cells of BDF1 mice cease to produce inhibitory activity in contrast to similar cells of control animals. Therefore, increased CFUs proliferation in immunized mice can be due to decreased production of inhibitory activity and resulting abundance of stimulating factors. In BAlB/c mice CFUs proliferation is not changed after antigen injection and their bone marrow cells continue to synthesize inhibitory substances. Differentiation of CFUs into committed blood precursor cells may depend on the proliferation level in CFUs population since activation of CFUs proliferation in immunized BDF1 mice is accompanied by a decreased number of CFU GM and CFU-M but an increased number of BFU-E. It should be noted that intact BAlB/c mice show a high level of CFUs proliferation similar to that of immunized BDF1 mice. PMID- 1857596 TI - [The behavior of the X chromosomes in intra- and interspecific hybrid cells of murine teratocarcinoma PCC4azal]. AB - We have demonstrated that X chromosomes are reactivated in hybrids obtained by fusion of mouse PCC4azaI teratocarcinoma cells (XO, 39HPRT-) with splenocytes from mouse females heterozygous in Hprt gene. These hybrids are capable of spontaneous differentiation. We also obtained similar interspecies hybrids of PCC4azaI cells with bone marrow cells of the American mink. The majority of such hybrids remained undifferentiated, however, after long-term cultivation at high cell density they differentiated into epithelial- or fibroblast-like cells similarly to PCC4azaI cells. Two hybrids had the autosomal complement of the mouse and two X chromosomes (mouse and mink); both X chromosomes were active. These X chromosomes were not inactivated during differentiation in vitro. PMID- 1857597 TI - [Genetic control over the determination and proliferation of melanocyte stem cells in mammals]. AB - Data obtained in mutant mouse strains provide evidence for multilocus control of determination and proliferation of melanocyte stem cells. Mice are known to have five loci (mi, Sp, s, Ls, Dom) controlling melanoblast determination. Locus mi is expressed in pluripotent cells of the neural crest from which melanocyte and neuron clones are formed; it is also expressed in a strain of ectomesenchyme cells. Loci Sp, s, ls and Dom are expressed somewhat later, probably during one of the last quantal cell cycles leading to the determination of unipotent melanocyte stem cells. Mutant genes of these loci impair the development of pigment cells as well as of ganglial neurons. Three loci (W, vs, Sl) control the proliferation of melanocyte stem cells. Mutations of locus W present in a single copy inhibit the proliferative activity of melanoblasts, whereas when present at the double dose they completely block their proliferation. Locus Sl is not expressed in melanocytes but acts in another cell system, which is very important for the proliferation of melanocyte stem cells. Mutant genes Ga, si and vit decrease the lifespan of stem cells for epidermal melanocytes. PMID- 1857598 TI - [The determination of the cytodifferentiation of the adenohypophysis in embryonic development]. AB - This is a review of the literature and author's own data on determination of various cell types of adenohypophysis during embryonic development. Recent studies using techniques of organ culture and immunohistochemistry have established the time of determination of glandular cells of adenohypophysis. It has been shown in rat embryos that the direction of differentiation of all major cell types of adenohypophysis is programmed late during the development of the epithelial anlage of this organ. Similar data as concerns somatotropic and prolactin cells have been obtained on chick embryos. Chick embryos possess regional type of determination of prolactin and somatotropin-containing cells in the anlage in correspondence with their location in definitive adenohypophysis. PMID- 1857599 TI - [The stem-cell reserve of the liver]. AB - This paper considers the problem of epithelial stem cells of the liver and possibilities of its experimental solution. Authors' own data obtained with the model of induced hepatocarcinogenesis in mice are discussed; the experiments were performed using electron microscopy, autoradiography and immunochemistry. In accordance with these data, Gering cells are stem cells of the liver, and oval cells correspond to committed precursors capable to differentiation in either hepatocellular or cholangiolar direction under the conditions of periportal microenvironment. We have also compared hepatocyte differentiation in preneoplastic mouse liver and regenerating pancreas of adult rats (Rao et al. Amer. J. Pathol. 1989. V. 134. P. 1069-1086). We also discuss stem cell compartment organization in organs having glandular structure and the possibility of existence in the adult of non-committed multipotent cells capable of producing various types of differentiation in tissues having common origin during embryogenesis. PMID- 1857600 TI - [Osteogenic stem cells of the bone marrow]. AB - This paper presents literature and author's own data demonstrating that bone marrow contains determined osteogenic precursor cells with high potential to differentiation. They are stem cells of the bone and belong to the stromal cell line of the bone marrow which is histogenetically independent of hemopoietic cells. The paper presents detailed analysis of bone marrow stromal cells (CFUf) as well as of their osteogenic properties and requirements in growth factors. In conclusion mutual growth-stimulating interactions in the system of hemopoietic stromal cells are reviewed. PMID- 1857601 TI - [New differentiation markers of mouse liver epithelial cell lines]. AB - We describe two new markers of mouse liver epithelial cells detected by monoclonal antibodies. Immunomorphological localization of antigens was performed using light and electron microscopy. Antigen G7 is a marker of cholangiocytes and oval cells. Antigen A6 is present in cholangiocytes and oval cells; moreover, it is expressed in normal liver in single hepatocytes adjacent to the portal vein, in preneoplastic liver, in newly formed hepatocytes, and in certain hepatocarcinomas. Thus, antigen A6 is a marker of cholangiocytes, oval cells and of certain stages of hepatocyte differentiation. We also detected phenotypic heterogeneity of Gehring cells in terms of antigen A6 content. We have formulated problem of the relationship between A6-negative Gehring cells and liver stem cells. Both marker antigens are species-specific but are not specific for the liver. Antigen A6 is simultaneously a differentiation marker of cells belonging to the erythroid series. It is expressed in erythroblasts of fetal liver and is absent in erythroblasts of the yolk sac and erythrocytes. The relationship between antigen A6 and blood group antigens is discussed. PMID- 1857603 TI - [An interview with Prof. T. M. Dexter (by I. Tsyrlova)]. PMID- 1857602 TI - [A biochemical analysis of the differentiation of the epithelial stem cells of the crystalline lens in amphibians]. PMID- 1857604 TI - [The validity of the universality of "rule 2k" for cellularity]. PMID- 1857605 TI - [Importance of the detection of minimal residual disease in the management of acute leukemia]. AB - Between 1984-1988, 57 adult acute leukemic patients were treated with intensive combined chemotherapy in the National Institute of Haematology and Blood Transfusion. For the evaluation of response to therapy, 4 investigations were performed in parallel: bone marrow aspirate, bone marrow biopsy, cytogenetic analysis and bone marrow culture. Nonparametric test for samples taken for the evaluation of remission status showed that bone marrow biopsy was significantly the most sensitive method for the detection of residual disease. The bone marrow culture was also on the borderline of significance, but the low CFU-GM level did not always correlate with the further clinical course. Occasionally, karyotypic abnormality was the only sign of the residual disease. It would be of great importance to quantitate the minimal residual disease in order to evaluate and compare the various intensive postinduction therapeutic strategies. PMID- 1857606 TI - [Decreased serum osteocalcin level in non-alcoholic and alcoholic chronic liver diseases]. AB - Serum level of osteocalcin (OC) is believed to be a specific biochemical parameter of bone formation. Decreased serum OC has been reported in alcohol intoxicated subjects, in patients with primary biliary cirrhosis and in patients with chronic alcoholic liver disease. The question was, whether lower OC level could be detected in patients with nonalcoholic and non-cholestatic chronic liver disease. The serum OC was measured by RIA developed in our laboratory. Results were compared to age and sex matched controls. Decreased OC level was found in 35 out of 47 (74%) patients with non-alcoholic and non-cholestatic liver disease as chronic persistent hepatitis, chronic active hepatitis, fatty liver and cirrhosis, in 21 out of 26 (80%) patients with alcoholic liver disease and in 8 out of 15 (53%) primary biliary cirrhosis. None of the patients had elevated value. There was no correlation between the decreased OC level and the duration or severity of the liver disease and the laboratory parameters as bilirubin, AST, ALT, alkaline phosphatase, albumin, prothrombin, and serum 25-OH-D3 vitamin level. Decreased OC was found also in the patients without cirrhosis. The possible causes are discussed. Relying upon these findings it is supposed that chronic liver disease by itself can influence the osteoblast activity also by some unknown mechanism. PMID- 1857607 TI - [Family studies in idiopathic hypercalciuria]. AB - Increased urinary calcium excretion was found in 20 of 42 family members of 14 children with idiopathic hypercalciuria. Analysis of questionnaires on environmental factors and of pedigrees suggested that familial occurrence of absorptive hypercalciuria was mainly due to common alimentary practice. At the same time, the existence of an autosomal dominant form of renal hypercalciuria seems to be very likely, the mechanism of which is not yet understood. PMID- 1857608 TI - [Arthroscopy in pediatric orthopedics]. AB - Based on his own material, author for the first time in the Hungarian literature discusses the special points of arthroscopy in childhood and adolescence. Within a period of 18 months, 64 knee arthroscopies were performed on patients with the mean age of 14.9 years. In 17 cases arthroscopy was followed by surgical exposure of the joint, while 14 of the cases remained only diagnostic interventions. Arthroscopic intraarticular surgery was performed in 33 knees. Based on the analysis of the latter two groups it is stated that arthroscopy has its value in the fields of pediatric orthopaedics. PMID- 1857610 TI - Clinical audiology. PMID- 1857609 TI - [Public health in the Esztergom region in the 18th century]. PMID- 1857611 TI - Measurement of sound. AB - The measurement of sound involves the analysis of frequency, intensity, and temporal dimensions of acoustic signals. Each dimension of sound can be related directly to clinically observed phenomena. Frequency information, measured in Hz, can be extracted from pure-tone and complex stimuli. Intensity represents the physical energy of a signal and is described by using the decibel scale--a logarithmic scale of ratios. Temporal characteristics of sound include duration, phase, and repetition rate. In the analysis of human hearing sensitivity, the middle ear system and its impedance characteristics also must be considered. In this article, we have reviewed some major principles of sound and have presented a series of practical clinical applications. Such principles as these help to predict and explain frequency of laryngeal tones, middle ear mechanics, ear canal resonance, real-ear measurements of hearing aids, the Articulation Index, hearing loss, understanding of speech in quiet and in noise, and the relation between hearing and speech. PMID- 1857612 TI - Basic hearing tests. AB - This article contains a discussion of pure-tone and speech audiometry as these measures relate to primary audiologic evaluation of hearing. The scientific foundation underlying the development of stimulus-specific standards for normal hearing, test materials, and methods for basic tests are included. A rationale for test administration, masking, and interpretation of results is presented. PMID- 1857613 TI - Behavioral audiometry. AB - Behavioral audiometry is based on observation of overt responses to controlled auditory stimuli, as contrasted with electrophysiologic procedures, which involve electrophysiologic monitoring or direct recording of the bioelectric correlates of the original signal. When reinforcement is added to the behavioral procedures, the infant or young child provides highly reliable responses, and it is possible to test most infants 6 months of age and older with these procedures. The combination of both behavioral and electrophysiologic procedures can resolve most clinical questions regarding the auditory function of young infants and children. PMID- 1857614 TI - Basic principles and clinical applications of tympanometry. AB - This article presents an overview of tympanometric measures using a 226-Hz probe tone, with an additional focus on complex admittance measures at 678 Hz and an introduction to multiple frequency tympanometry. Basic principles underlying all admittance measures are presented. The clinical implementation and interpretation of tympanometry is discussed. PMID- 1857615 TI - Acoustic reflex measures in audiologic evaluation. AB - Measurement of the acoustic-stapedius reflex is useful in the diagnosis of certain otologic diseases. The anatomy and physiology of the middle ear muscles and the acoustic reflex arc are reviewed for normal and pathologic ears. The application of acoustic reflex measures to clinical diagnosis is illustrated by a series of case studies. PMID- 1857616 TI - Auditory evoked potentials. AB - Auditory evoked potentials (AEPs) have become an integral part of the current otologic/audiologic test battery. With these techniques, synchronous neural activity can be examined from the peripheral end organ of hearing up to the cortical structures responsible for audition. The clinical applications of AEPs range from their use as an indicator of auditory sensitivity in patients who either cannot or will not respond in a conventional behavioral test situation to their use in the diagnosis and monitoring of various otologic and neurologic disorders. As such, measurement of AEPs allows the clinician a unique glimpse of the auditory system. PMID- 1857617 TI - Central auditory function. AB - Central auditory disorders in children and adults have become more widely recognized in patients seen by otolaryngologists and audiologists. This article briefly defines those clinical entities, discusses the historic background of testing, and describes current and future test approaches to assessment of central auditory disorders. PMID- 1857618 TI - Pseudohypacusis. AB - This article provides the basis for the techniques and interpretation of audiologic tests useful in evaluation of the patient with pseudohypacusis. Differences between the childhood and adult forms of the problem are discussed. The indications for currently popular conventional and special tests are presented. These include both behavioral and electrophysiologic measures for assessing auditory function. PMID- 1857619 TI - Occupational hearing conservation. AB - Chronic exposure to high-intensity noise can produce permanent hearing loss, the amount of which depends on noise intensity, temporal and spectral characteristics, and the length of exposure. OSHA regulates workplace noise exposure in accordance with the Hearing Conservation Amendment of 1983. When noise levels equal or exceed an 85 dBA time-weighted average (TWA), the employer is required to provide annual audiometric screening. When noise levels exceed 90 dBA TWA, the worker's exposure must be reduced by engineering methods, administrative changes, or personal hearing protectors. If a worker demonstrates a standard (significant) threshold shift (10 dB or greater increased average hearing threshold at 2, 3, and 4 kHz in either ear) that is attributed to noise, the worker's exposure must be further reduced by one of the aforementioned methods. PMID- 1857620 TI - Hearing aid evaluation and fitting. AB - Although many patients with hearing loss benefit from medical or surgical intervention, the vast majority have noncorrectable hearing disorders for which rehabilitation through amplification is indicated. There are three goals for the application of hearing aids: (1) to amplify normal conversational speech to levels that are maximally understandable to the patient; (2) to help the patient hear other environmental sounds; and (3) to assist in the educational or habilitative process for those children who sustain hearing loss prior to language and speech development. In addition, there are certain issues that require medical consideration when a wearable device is placed in the ear. This article describes current hearing aid technology; reviews its benefits, limitations, and application for typical patients; discusses the medical aspects of hearing aid fitting; and describes new hearing aid technology on the horizon. PMID- 1857621 TI - Aural rehabilitation. AB - Aural rehabilitation involves a complete evaluation of the communication deficits and needs of the hearing-impaired patient as well as the provision of counselling and therapy. This article describes listening-assistive devices, speech production, and audiovisual training. Issues related to educational placement and tinnitus also are reviewed. PMID- 1857622 TI - Vestibular testing in hearing loss. AB - The basic electonystagmography battery (saccade, gaze, position, caloric tests, and spontaneous nystagmus) are described along with rotational testing and dynamic posturography. Emphasis is placed on interpretation, relative benefits, and limitations as an aid in diagnosis. PMID- 1857623 TI - Contrast thresholds for identification of numeric characters in direct and eccentric view. AB - Aubert and Foerster (1857) are frequently cited for having shown that the lower visual acuity of peripheral vision can be compensated for by increasing stimulus size. This result is seemingly consistent with the concept of cortical magnification, and it has been confirmed by many subsequent authors. Yet it is rarely noted that Aubert and Foerster also observed a loss of the "quality of form." We have studied the recognition of numeric characters in foveal and eccentric vision by determining the contrast required for 67% correct identification. At each eccentricity, the lowest contrast threshold is achieved with a specific stimulus size. But the contrast thresholds for these optimal stimuli are not independent of retinal eccentricity as cortical magnification scaling would predict. With high-contrast targets, however, threshold target sizes were consistent with cortical magnification out to 6 degrees eccentricity. Beyond 6 degrees, threshold target sizes were larger than cortical magnification predicted. We also investigated recognition performance in the presence of neighboring characters (crowding phenomenon). Target character size, distance of flanking characters, and precision of focusing of attention all affect recognition. The influence of these parameters is different in the fovea and in the periphery. Our findings confirm Aubert and Foester's original observation of a qualitative difference between foveal and peripheral vision. PMID- 1857624 TI - Sensorimotor synchronization: motor responses to regular auditory patterns. AB - Subjects (N = 32) were asked to synchronize a motor response with tones in auditory patterns. These patterns were created from six tones and six intertone intervals of equal duration. The pitch of the first tone differed from the others. It was found that subjects used three types of timing in their motor response: (1) the first intertone interval was prolonged and the second interval was shortened, (2) the second intertone interval was prolonged and the first interval was shortened, and/or (3) the first interval and the second interval were of approximately the same length. The prolongation of the fifth interval was observed during all three types of timing. The results are explained using the concept of suprasegmental control of timing, which explains a prolongation of intervals at critical control point of the patterns. The occurrence of three different strategies of timing is discussed in connection with similar principles in musical performance. PMID- 1857625 TI - Time course of recovery from gustatory adaptation to NaCl. AB - Recovery from adaptation to NaCl was tested by comparing some relevant parameters of response to the adapting and test stimuli separated by different recovery intervals. The time course of response was determined using magnitude estimations and using the flow chamber for stimulus delivery. The course of recovery for all parameters used was a negatively accelerated function of the rest time, but the recovery rate of different parameters did not prove to be equal. Recovery was fastest for the initial maximum taste magnitude, followed by the time needed for the taste to disappear. The taste effect summed over time and the time required for the taste magnitude to decrease to 30% of its preadapted maximum were the slowest to recover. Although the recovery processes proceeded at a rapid rate during the initial period, all parameters remained depressed over a rather long period. PMID- 1857626 TI - Apparent reversals of a rotating mask: a new demonstration of cognition in perception. AB - A mask of a face rotated about its vertical axis of symmetry can appear to oscillate rather than rotate. Do stimulus features (e.g., shape) or cognitive factors (e.g., differential familiarity with convex and concave views of faces) explain this new illusion? In Experiment 1, differential familiarity was varied across stimuli by using familiar and unfamiliar objects rotating at 4 rpm and within stimuli by showing the objects upright and inverted. True motion was seen more with unfamiliar objects than with familiar objects and more with an inverted mask than with an upright mask. The results of Experiment 2, which was done with static views, suggest that the upright and inverted masks present similar structure to the visual system. In Experiment 3, the objects were shown rotating at 8 rpm; the results are similar to those of Experiment 1. These experiments favor a differential familiarity account of this illusory motion. Cognitive constraints on perceived motion and perceived rigidity are discussed. PMID- 1857627 TI - Manual discrimination of force using active finger motion. AB - In these experiments, two plates were grasped between the thumb and forefinger and squeezed together along a linear track. An electromechanical system presented a constant resistance force during the squeeze up to a predetermined location on the track, whereupon the force effectively went to infinity (simulating a wall) or to zero (simulating a cliff). The task of the subject was to discriminate between two alternative levels of the constant resistance force (a reference level and a reference-plus-increment level). Results of these experiments indicate a just noticeable difference of roughly 7% of the reference force using a one-interval paradigm with trial-by-trial feedback over the ranges 2.5 less than or equal to F0 less than or equal to 10.0 newtons, 5 less than or equal to D less than or equal to 30 mm, 45 less than or equal to S less than or equal to 125 mm, and 25 less than or equal to V less than or equal to 160 mm/sec, where F0 is the reference force, D is the distance squeezed, S is the initial fingerspan, and V is the mean velocity of the squeeze. These results, based on tests with 5 subjects, are consistent with a wide range of previous results, some of which are associated with other body surfaces and muscle systems and many of which were obtained with different psychophysical methods. PMID- 1857628 TI - The effect of training on visual alignment discrimination and grating resolution. AB - The effect of training on an observer's ability to detect the misalignment of three points, a hyperacuity, and to resolve a six-line grating was studied in a transfer-of-training design with observers (4 in each of two experiments) who were experienced in making psychophysical judgments of other visual stimuli. The transfer-of-training design enabled us to look for any training-based improvement. Long periods of training produced no statistically significant improvement in performance under any condition. There were small practice-based improvements, but the primary patterns indicated threshold fluctuation rather than improvement. We interpret the results to indicate that the neural mechanisms underlying three-point alignment and grating discrimination, like those for gap bisection (Klein & Levi, 1985), are not malleable to any significant extent. PMID- 1857629 TI - Motion capture by a frame: global or local processing? AB - The possibility that frames serve to capture lines within them so that they appear on a coplanar surface was investigated, using coherence in direction of rotary motion (Gillam, 1972) as a quantitative measure of the coplanarity of frame and internal lines. It was found that perceptual coherence between a pair of lines was greatly increased by surrounding them with a frame, if the frame was perspectivally consistent with the lines. A second experiment showed that this grouping can be attributed to a global effect of the frame and cannot be accounted for by local grouping of the internal lines with components of the frame. PMID- 1857630 TI - The effects of complexity on the perception of vibrotactile patterns. AB - Vibrotactile patterns were presented to subjects' left index fingerpads using the array from the Optacon. A set of simple (one-line) patterns and a set of complex (two-line) patterns were constructed so that they were equally identifiable when presented individually. In Experiment 1, discrimination performance was lower for two-line patterns than for one-line patterns. Communality, the number of lines that two patterns share in common, appeared to be the major factor in reducing discrimination performance for two-line patterns. Experiment 2 measured the time required to identify individual patterns. There was no significant difference in identification times for one- and two-line patterns, suggesting that features within a pattern were processed simultaneously. In the presence of a temporal masking stimulus (Experiment 3), two-line patterns were more difficult to identify than one-line patterns, but reaction times were similar for the two sets of patterns. The results suggest that varying complexity affects perception of patterns at later stages of processing. PMID- 1857632 TI - An "open-transformed scale" for correcting ceiling effects and enhancing retest reliability: the example of pain. AB - The use of closed scales (with anchors at each end) to measure pain was found to produce ceiling effects characterized by a deceleration of ratings toward the upper end of the scale. This was consistent with previous research. Apart from producing nonlinear functions, the closed scale also limited test-retest reliability because of subjects' tendencies to correct their distorted ratings in subsequent trials. However, an open-ended scale coupled with transformation of reported ratings into a decile scale virtually eliminated the ceiling effect, thus producing consistently linear functions and maximizing test-retest reliability. This finding may have implications for the measurement of other sensory and psychological phenomena, especially those in which the property evaluated varies in a continuous fashion. PMID- 1857631 TI - A weighted-average model of achromatic transparency. AB - A model of achromatic transparency based on the idea that neural representations of transparency are activated by proximal contours is described. It is proposed that the weighted average of the magnitudes of the representations of transparency relative to a perceived continuous transparent surface corresponds to the judgement of the overall degree of transparency of the same surface. Tests of this weighted-average model were carried out with bistable patterns formed by two overlapping surfaces that appeared opaque where they were superimposed on the background and transparent where they were superimposed on each other (partial transparency). In agreement with predictions from the weighted-average model, the rated degrees of transparency of these two surfaces were noncomplementary and independent of background reflectance. Two experiments confirmed the contention of this model that the relevant proximal contours for the judgement of partial transparency of the two overlapping transparent surfaces in a bistable pattern correspond to the part where these surfaces are superimposed. PMID- 1857633 TI - Does intermittence in induced rotary movement have any explanatory significance? AB - Induced rotary movement has been reported to start and stop repeatedly during 1 min of observation. This has been taken as evidence for the involvement either of cyclorotational optokinetic nystagmus or of roll vection. Both assertions are dubious. Regarding cyclorotational optokinetic nystagmus, available evidence shows that it is too weak to be important in induced rotary movement. Also, induced rotary movement and cyclorotational optokinetic nystagmus are affected differently by the velocity of eliciting stimulation. Regarding roll vection, the conditions for its intermittence do not match those for induced rotary movement. Also, although aftereffects for induced rotary movement are negative, those for roll vection are positive and negative. Intermittence in induced rotary movement may be parsimoniously explained as characteristic of a weak effect. PMID- 1857634 TI - Reoxygenation-induced arrhythmogenic transient inward currents in isolated cells of the guinea-pig heart. AB - Transient inward currents (Iti), activated by a rise in intracellular Ca concentration, are believed to trigger cardiac arrhythmias in reperfused hearts. In this report, Iti in isolated cardiocytes from the guinea-pig were evoked by reoxygenation following a period of anoxia of between 4 min and 35 min. Reoxygenation was performed 1 min after the full development of an anoxia-induced time-independent K current. This current disappeared within 2-6 s and in the following 10 s Iti developed to maximum amplitude. Iti were evoked using a constant pulse pattern (holding potential Vh = -45 mV; test potential Vt = +10; pulse duration 350 ms; frequency 1 Hz). In more than 95% of the cells, Iti at the holding potential Iti (-45 mV) declined with a time constant of tau = 670 +/- 240 ms (mean +/- SD, n = 17). In two cells, undamped oscillatory currents were observed. The amplitude of Iti (-45 mV) was proportional to the amplitude and duration of the preceding depolarizing test pulse. Test pulses of long duration (500 ms and 1000 ms, mean +/- SD) to potentials positive to +10 mV produced slowly decaying tail currents (tau = 391 +/- 51 ms, mean +/- SD), which superimposed with Iti (-45 mV). The current/voltage relationship of Iti peaked between -30 mV and -10 mV and approximated zero at the most positive potentials, i.e. no reversal of Iti was found up to +80 mV. Using double-pulse protocols (prepulse potential +40 mV), Iti were enhanced at potentials negative to -30 mV and were also present in the range of the normal resting potential of ventricular heart cells. The instantaneous current-voltage relationship was monotone between 50 mV and +40 mV. Because of the dependence of Iti on the preceding depolarization, the instantaneous current-voltage relationship provides more reliable information on the voltage dependence of Iti. The interval between two subsequent Iti (-45 mV) values was 237 +/- 35 ms (mean +/- SD, n = 27) and depended on the amplitude of Iti (-45 mV) to increase by 5.2 +/- 0.5% (mean +/- SD) per 100 pA decrease in Iti (-45 mV). A simple noise analysis showed that if one assumes that ionic channels are responsible for the generation of Iti (-45 mV), their unitary conductance cannot exceed 0.36 pS. We conclude that reoxygenation-induced Iti are triggered by a cyclic release of Ca from the sarcoplasmic reticulum and provide evidence that they are mediated by the electrogenic Na/Ca exchanger.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1857638 TI - Biomechanics and the wheelchair. AB - Wheelchair biomechanics involves the study of how a wheelchair user imparts power to the wheels to achieve mobility. Because a wheelchair can coast, power input need not be continuous, but each power strike can be followed by a period of recovery, with the stroking frequency depending on user preferences and the coasting characteristics of the wheelchair. The latter is described in terms of rolling resistance, wind resistance and the slope of the surface. From these three factors the power required to propel the wheelchair is determined, and must be matched by the power output of the user. The efficiency of propulsion is the ratio of this power output to the metabolic cost and is typically in the order of 5% in normal use. The features required in a wheelchair depend upon user characteristics and intended activities. The ideal wheelchair for an individual will have the features that closely match these characteristics and activities. Thus prescription is not just choosing a wheelchair, but choosing the components of the wheelchair that best serve the intended purpose. In this paper, each component is examined for available options and how these options effect the performance of the wheelchair for the individual. The components include wheels, tyres, castors, frames, bearings, materials, construction details, seats, backrests, armrests, foot and legrests, headrests, wheel locks, running brakes, handrims, levers, accessories, adjustments and detachable parts. Each component is considered in relation to performance characteristics including rolling resistance, versatility, weight, comfort, stability, maneouvrability, transfer, stowage, durability and maintenance. Where they exist, wheelchair standards are referred to as a source of information regarding these characteristics. PMID- 1857639 TI - The design of attendant propelled wheelchairs. AB - The attendant operated wheelchair is propelled by applying forces to handles at the rear of the chair. There are no published data to justify the design of pushing handles on existing wheelchairs. In Dundee, studies of pushing have been conducted in order to obtain subjective preferences for location and design of handles and an understanding of biomechanical factors associated with wheelchair pushing. Preferred positions for handles have been found to be in the region of 0.75 of shoulder height, 1.14 times shoulder width although deviations of +/- 5% in these values are still rated as acceptable. The preferred positions do not correspond to minimum levels of resultant force or with lowest levels of moment in any of the upper body joints. Moments occurring at the lower back are not substantially affected by handle position. The biomechanical analysis so far has not revealed why some handle positions are more comfortable for pushing than others. Further study, involving calculation of resultant moments (rather than just sagittal plane moments) at these joints and at the lower body joints, is a next step in attempting to find the indicators of discomfort. Transferring a patient from or to a wheelchair can be a difficult operation with risks of accidents to the patient through falling and risks to the attendant of strain, particularly to the back. Current footrests on wheelchairs are a major source of the problems during transfer. A new approach to footrest design is described which solves these difficulties by using a footrest that lowers onto the floor. This has other attractive features such as providing good stability and restraint of the chair during transfer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1857641 TI - Wheelchair occupant restraints in motor vehicles. AB - The issue of safety for wheelchair users in motor vehicles has been raised in Australia by parents of young people with disabilities. Investigations revealed that wheelchair users were not covered by any legislated safety requirements, and each case received special dispensation from compliance with regulations covering the able-bodies population. Dynamic testing of restraint systems at the University of Michigan had revealed that existing systems were unsafe. Dynamic tests confirmed those findings on systems used at that time in Australia. Testing led to the design, development and marketing of a new wheelchair occupant and restraint system which remains a system of choice for use by organisations where the same people use the same buses in the same position each day. Australian Standard 2942-1987, Wheelchair Occupant Restraint Assemblies for Use in Motor Vehicles, has since been developed. It establishes design and performance requirements for these restraints and includes details of dynamic testing procedures. This paper describes the development of the above restraint system and the subsequent Australian Standard. PMID- 1857640 TI - Pushchairs. AB - Pushchairs for adults are used by two distinct groups: the high dependency users who cannot walk or use a self-propelling chair and the occasional users who may be able to walk indoors but are unable to walk significant distances outdoors. In the past, both disparate groups were provided with similar wheelchairs described as Model 9 or Model 10 in the United Kingdom. For the high dependency user the wheelchair may be individually adapted to accept specialized supportive seating and pressure relief cushions. The standard wheelchair without adaptation is supplied to the occasional user. For disabled children, the UK wheelchair service provides about 1200 pushchairs and buggies. About 400 of those are the more specialized type such as the Avon, while the rest are standard children's buggies, openly available at a High Street shop. The continued free supply of the standard buggy through the UK Wheelchair Service is questionable. A recent survey carried out by the UK Wheelchair Service showed that prescribers were not aware of the importance of lightness., foldability and appearance to parents and carers and conversely that parents often did not understand the necessity for supportive seating. The prevention of deformities in children by providing correctly supportive wheelchair seating is accepted. The Disablement Services Authority in the UK is investigating the possibilities of producing children's wheelchairs that will satisfy the requirements of user, parent and prescriber. PMID- 1857636 TI - Characterization of an outward K+ current in freshly dispersed cerebral arterial muscle cells. AB - This study was carried out to define some of the cellular ionic mechanisms controlling cerebral arterial muscle. Muscle cells were enzymatically dispersed from cat cerebral arteries. Cells were dialyzed and voltage-clamped using patch pipettes and whole-cell currents measured. Using pipette solutions allowing us to record K+ currents we identified an outward current elicited by depolarizing voltage steps beyond -20 mV. This outward current exhibited properties of delayed outward rectification having a peak macroscopic current at +90 mV of 504 +/- 236 pA. The current was sensitive to 4-aminopyridine, but was sensitive to tetraethylammonium only at very high doses. When CsCl was in the recording pipette, macroscopic outward currents could not be recorded. Variations in the extracellular Ca2+ concentration from 0.5 to 5.0 mM had no effect on current amplitude or voltage dependence; similarly the Ca2+ channel blockers nifedipine and Mn2+ were without effect on this outward current. The current inactivated slowly with no decay seen even with 3-s command pulses. Repetitive voltage pulses from -60 to +90 mV at a frequency of 1 Hz resulted in "cumulative reduction", depressing peak current by 60% after ten pulses. Upon reduction of pH from 7.43 to 7.20 we observed a 350% increase in peak outward current in 7 of 12 cells studied in this regard. Thus, the cellular mechanism responsible for cerebral vascular dilation to acidosis and/or hypercapnia may involve an increase in outward K+ current. PMID- 1857642 TI - Informing the media. PMID- 1857637 TI - Clinical trial of a computer-aided system for orthopaedic shoe upper design. AB - A trial has been conducted to produce the uppers for orthopaedic shoes using an existing commercial computer-aided design system. The aims of the trial were to confirm that a CAD system developed for the volume shoe trade (Shoemaster from Clarks Shoes) could be used for the upper design of orthopaedic shoes and to assess the contribution of professional shoe design on cosmesis and acceptability of these shoes. A small number of adult diabetic patients and children with foot deformities were selected, all of who had previously been prescribed and issued with special shoes. The existing lasts for these patients were digitised, and new styles developed on the CAD system over a 3D image of the last. Pattern pieces were cut automatically and the uppers closed. Lasting was done as normal at the two collaborating orthopaedic companies and the shoes supplied to the patients. The CAD system proved successful in coping with orthopaedic last shapes and shoe requirements. Professional design produced fashionable and cosmetically-pleasing styles within the constraints imposed by the underlying medical conditions. PMID- 1857635 TI - A high-conductance Ca(2+)-activated K+ channel in cultured human eccrine sweat gland cells. AB - Recordings have been made of a potassium-selective ion channel in primary cultures of cells derived from explants of human eccrine sweat glands obtained from normal subjects and from subjects suffering from cystic fibrosis. There appears to be no functional difference between potassium channels derived from normal subjects and those from cystic fibrosis subjects. The channel falls into the group generally known as "Maxi-K" channels, and has a slope conductance, with symmetrical solutions in bath and pipette containing 140 mM K+, of approximately 230 pS. It is calcium-activated, pH-sensitive and can be blocked by barium and quinine. The channel appears only very rarely in patches derived from confluent cells (in approximately 1 in 30 patches containing channels), but it is more frequently observed in younger cultures of dividing cells derived from recently explanted (within the previous 48-72 h) glands. It is possible that this channel is normally located on the basolateral membrane of the cell, and is responsible for the calcium-dependent secretory and absorptive events seen in the intact sweat gland. PMID- 1857644 TI - Perceived well-being of persons quitting smoking. AB - The purpose of this study was to examine the perceived well-being of persons who are smokers, nonsmokers, or are quitting smoking. The sample included 74 nonsmokers, 74 smokers, and 92 self-defined quitters. Subjects' well-being was examined controlling for the effects of daily hassles and selected demographic differences. Measures of well-being included general health, morale, physical, and psychological symptoms. Scores for intensity of daily hassles were significantly higher, and well-being scores lower, for persons quitting smoking compared to smokers and nonsmokers. Further, even after controlling for the effects of daily hassles on well-being, persons quitting smoking had significantly lower levels of well-being than did smokers or nonsmokers. PMID- 1857643 TI - Psychologic and physiologic aspects of acute dyspnea in asthmatics. AB - The purpose of this study was to compare psychologic and physiologic variables during intense dyspnea to those at times of no or low dyspnea in people with asthma. Thirty-six adults ranging from 19 to 76 years old were tested when they first came to the emergency department in acute dyspnea and again when they had no or low dyspnea just prior to discharge. Clinical signs found to be higher during high dyspnea than low dyspnea were respiratory rate, pulse, wheezing, and accessory muscle use. Peak expiratory flow rates and oxygen saturation were significantly lower, while anxiety, depression, somatization, and hostility were higher during times of high dyspnea. The panic/fear, fatigue, dyspnea, hyperventilation/hypocapnia, congestion, and rapid breathing subscales of the Asthma Symptom Checklist were also higher during high dyspnea compared to low dyspnea. PMID- 1857645 TI - The abdomen, thigh, and arm as sites for subcutaneous sodium heparin injections. AB - The purpose of this study was to evaluate three subcutaneous injection sites for low-dose heparin therapy (5,000 units). One hundred and one subjects were randomly placed in one of three groups. Group A received injections in the abdomen, Group B, in the thigh, and Group C in the arm. Each subject received three injections at the one site. Activated partial thromboplastin time (APTT) was measured prior to initiation of heparin and again four hours after the first injection. Bruising was measured at 48, 60, and 72 hours postinjection. There were no statistically significant differences among groups for either changes in APTT or bruising at 60 and 72 hours postinjection. Thus the clinical practice of utilizing the abdomen as the only or preferred site for subcutaneous heparin injections was not supported. PMID- 1857646 TI - Psychosocial predictors of maternal depressive symptoms, parenting attitudes, and child behavior in single-parent families. AB - The purposes of the study were to identify psychosocial predictors of depressive symptoms among low-income, single mothers and to investigate the effects of maternal psychosocial factors, depressive symptoms, and parenting attitudes on children's behavior. In-home interviews were conducted with 225 mothers to obtain data on their everyday stressors, coping strategies, social resources, depressive symptoms, and parenting attitudes, as well as reports of their children's behavior. High depressive symptoms occurred among 59.6% of the women. Higher depressive symptoms were associated with greater everyday stressors, fewer social resources, and greater use of avoidance coping. Neither social resources nor coping strategies buffered the relationship between everyday stressors and depressive symptoms. Maternal depressive symptoms predicted parenting attitudes. Parenting attitudes, in turn, predicted child behavior. These findings suggest that depressive symptoms are indirectly associated with mothers' reports of child behavior through their influence on parenting attitudes. PMID- 1857647 TI - Type A behavior in children: psychometric properties of the Matthews Youth Test for Health. AB - The purpose of this study was to investigate the psychometric properties of the Matthews Youth Test for Health (MYTH) as a measure of components of Type A behavior in school-age children. The sample consisted of 216 middle-class, white, 6 to 11 year old, same-sex twin children. Pairs were randomly split into two subgroups for cross-validation. The MYTH was completed by 88% of the children's teachers. The Perceived Competence Scale was completed by 118 of the 124 children 8 to 11 years old; a parallel form of this instrument was completed by teachers of 108 of these children. The 17 items of the MYTH instrument were factor analyzed. Two factors, Impatience-Aggression and Competitive Achievement Striving, were derived and cross-validated. These MYTH factors were internally consistent and replicated previous studies of school-age children. The construct validity of the MYTH subscales was partially supported by evidence of relationships between these components of Type A behavior and teacher-ratings of the child's competence in specific domains. Children's ratings of their competence and perceptions of global self-worth were not related to total MYTH scores or subscale scores. PMID- 1857649 TI - Re: 'A review of the literature on cocaine abuse in pregnancy'. PMID- 1857648 TI - Applying the theory of reasoned action to AIDS risk behavior: condom use among black women. AB - This study tested hypotheses regarding attitudinal and normative influences on intentions to use condoms, a practice that would reduce women's risk of sexually transmitted HIV infection. Participants were 103 sexually active unmarried black women undergraduates at an inner-city commuter university, in an area with a high rate of reported AIDS cases among women. Consistent with the theory of reasoned action, multiple regression analysis on women's anonymous responses to a mailed survey revealed that those who registered more favorable attitudes toward condoms and those who perceived subjective norms more supportive of condom use reported firmer intentions to use condoms in the next three months. Key behavioral beliefs related to attitudes centered on the adverse effects of condom use on sexual enjoyment. Key normative influences were respondents' sexual partners and mothers. However, women's own attitudes were a stronger determinant of intentions to use condoms than were their perceptions of normative influences, particularly among women with above-average AIDS knowledge. The results suggest that the theory of reasoned action provides a potentially useful conceptual framework for interventions to change a key AIDS risk behavior among women. PMID- 1857650 TI - Re: 'Planning sample sizes: comparison of factor level means'. PMID- 1857651 TI - Uncertainty in illness theory: a replication of the mediating effects of mastery and coping. AB - The purpose of this investigation was to replicate a test of the mediating functions of mastery and coping and to determine whether the relationships found in the initial test of the model would hold with a sample more heterogenous than the original sample. One hundred women receiving treatment for gynecological cancer participated in the investigation. Of the 14 relationships in the model, only 5 replicated significant paths and had overlapping confidence intervals. Two moderators were proposed to explain the differences between the initial and replication tests of the model and to improve the specificity of the theory. PMID- 1857652 TI - Pain reduction interventions during neonatal circumcision. AB - The purpose of this study was to determine the effect of some noninvasive pain reduction interventions on pain in 121 neonates undergoing unanesthetized circumcision. Subjects were randomly assigned to one of six groups: classical music, intrauterine sounds, pacifier, music and pacifier, intrauterine sounds and pacifier, or control (no nurses present and no pain reduction interventions used). Physiological variables that were monitored were heart rate, rhythm, dysrhythmias, blood pressure, transcutaneous oxygen (tcpO2), rate pressure product, and behavioral state, measured during 14 circumcision steps. Over the 14 steps, 42% of the heart rates, 78% of the systolic blood pressures (SBP), 30% of the diastolic blood pressures (DBP), and 81% of the tcpO2 pressures were abnormal. Few significant differences were found among any of the steps. SBP and DBP differed significantly between groups during two of the noninvasive steps; and tcpO2 differed significantly during six steps. PMID- 1857653 TI - Changes in nutritive sucking patterns with increasing gestational age. PMID- 1857654 TI - *, **, and ***; statistical nonsense at the .00000 level. AB - Researchers who report statistical significance with *, **, ***, or p values are confusing statistical significance with clinical significance and are wasting time, money, and energy with studies that are either too precise, or more likely too imprecise. Therefore, researchers who value their time, money, and energy should avoid this outmoded statistical procedure, and present alpha to engage in the power calculation. PMID- 1857655 TI - Using slopes to measure directional change. PMID- 1857656 TI - Diary of a nurse. PMID- 1857657 TI - [AIDS and the oral cavity. Clinical aspects]. PMID- 1857658 TI - [Clinical evaluation of anesthesia using iontophoresis for pain control during scaling]. AB - A double blind study, cross-over in the same subjects compares the clinical efficacy of anesthetic application with iontophoresis versus placebo in the control of pain during scaling. None of ten subjects reported pain during scaling after iontophoresis with anesthetic, while six of ten reported pain after iontophoresis with placebo. PMID- 1857659 TI - [Progression of DMF index--DMF from 3 to 12 years: need for preventive intervention]. AB - To evaluate the prevalence of soft deposits and the trend of dmf/DMF index, a group of children between 3 and 12 years of age has been examined. A DMF Index of 5.74 at 12 proves the need to promote educational and prevention programmes in the Ulss 34 area since the WHO program "Health for all in the year 2000" sets a target of a DMF Index below 3 at 12. PMID- 1857660 TI - [Gloves for operator and patient protection: value, defects and limitations]. PMID- 1857661 TI - [The role of the dental hygienist in orthodontic practice]. AB - The success of orthodontic treatment depends, in part, upon the oral hygienic status of the patient and his active cooperation in the treatment. The purpose of this paper is to review the organization of a dental hygiene program in the orthodontic practice. Before treatment the dental hygienists should motivate the patient, teach him plaque control techniques, and remove hard and soft deposits; she can organize the gathering of documents necessary to the orthodontist to study the case. The author describes the components of the recall appointment, that must take place frequently during treatment; and suggests technical hints useful for the organization of a maintenance program after treatment. PMID- 1857663 TI - The Practitioner Education Programme. PMID- 1857662 TI - [Hygienists and assistants in Finland]. PMID- 1857664 TI - A child who has not been immunised. PMID- 1857665 TI - Techniques for distance learning. PMID- 1857666 TI - Nighttime behavioural problems. PMID- 1857670 TI - Pustular skin disease. PMID- 1857667 TI - Insurance forms. PMID- 1857669 TI - Treating the itchy patient. PMID- 1857668 TI - Critical evaluation and audit. PMID- 1857671 TI - Scaly lesions. PMID- 1857672 TI - Skin neoplasia. PMID- 1857673 TI - Psychological aspects of skin disease. PMID- 1857674 TI - PACT levels 1 and 2. PMID- 1857675 TI - Prescribing for children. PMID- 1857676 TI - [Early childhood violent and sexual traumatization]. AB - Violent and sexual child abuse represents an extreme traumatization that can continue to influence the lives of affected children into adulthood. Freud (1917) provided a concept of the influence of this extreme form of traumatization in his model of the traumatic neurosis. It is described as an after-the-fact attempt to master the flood of sensations that characterizes the trauma. More recent theoretical models identify a collapse of the ego during trauma as well as the effects of this collapse on the formation of self and object representants at the heart of the traumatic event. As a result of the collapse of the ego during trauma, the traumatized individual does not succeed in forming mature memories of the experience. Immature memories of trauma are marked by, among other things, very diffuse, near physical feelings that cannot be integrated into the ego (Cohen 1980). From the perspective of object relation theories, the lack of integration of "bad" and "good" self of the traumatized individual is emphasized by the abuser. Drawing on case studies, the authors illuminate the importance of the principle of the answer (Heigl-Evers/Heigl 1979, 1983) to the efforts to differentiate and integrate in the treatment of extremely traumatized patients. PMID- 1857677 TI - [Pathologic anxiety in the family]. AB - This is an attempt to present some anxiety syndromes of infancy in their psycho dynamic connections with the specific family situation. Particular anxiety conditions in the family are shown to cause psychic and psychosomatic consequences with children. A typical example of the network of intrapsychic and family causes of anxiety with separation anxiety, repressed aggression, and narcissistic conflict is the school phobia, which is dealt with in detail. PMID- 1857679 TI - [Stigmatizing patients at an inpatient unit of child and adolescent psychiatry]. AB - In a pilot study covering a sample of n = 25 children formerly treated as in patients within a child psychiatric unit and n = 40 parents of former in patients, approx. 30% of the parents indicated that their children had been exposed to stigmatizing behaviour reactions by their social environment in consequence of their stay at the unit. The children themselves felt stigmatized in approx. 50% of cases. Correlations between stigmatization and demographic variables, characteristics of treatment or subjects' attitudes towards child and adolescent psychiatry were rarely found to be significant. Because of their fear of stigmatization, there are tendencies among parents as well as patients to conceal the children's in-patient treatment, these tendencies sometimes even concerning the inner family circle. The paper stresses the need for child and adolescent psychiatry to face the problem of patient stigmatization and suggests possible steps to be taken in order to relieve or even prevent stigmatization. PMID- 1857678 TI - [The effectiveness of the Background Interference Procedure in psychiatric differential diagnosis of organic brain damage in children]. AB - The Background Interference Procedure (BIP) is an improved psychological test to discriminate brain damaged and non brain damaged adults. In the present study the efficiency of the BIP was compared to the psychometric standard for children, the Gottinger Formenreproduktions-Test, in a sample of 14 girls and 26 boys between 7 and 13 years with minimal brain dysfunction. The background interference condition increased significantly the error rate for the reproduction of the test items, and the BIP yielded a significant concurrent validity with neurological criteria. In particular, an impaired motor coordination was effectively predicted. It is concluded that the BIP is an efficient psychometric aid for determining the organic contribution to psychiatric syndromes in children. PMID- 1857680 TI - Electrophoretic elution of macromolecules from polyacrylamide or agarose gels. AB - A method for elution of micrograms of macromolecules from polyacrylamide and agarose gels is described. The recoveries were greater than 90% with three different macromolecules tested (28 to 360 kDa). An amount as small as 1 microgram of human serum albumin was eluted from polyacrylamide gel with 90% recovery. The eluted material is collected into a small chamber the size of which can be changed as required. Elution and concentration are achieved simultaneously and in one step under mild conditions. Sterile eluates can be obtained, if the apparatus is constructed under sterile conditions. PMID- 1857681 TI - Isolation of histone-like proteins from mitochondria of bovine heart. AB - Two methods for isolating and purifying histone-like proteins from mitochondria of bovine heart are described. In the first, a sonicated extract of the mitochondria was fractionated in three chromatography steps, including affinity chromatography on DNA-cellulose, to purify a protein that resembles very closely the histone-like protein (HM) of yeast mitochondria. In the second method, an acid extract of the heart mitochondria was the starting material; two other histone-like proteins were separated. Thus, as in mitochondria of Xenopus laevis, several histone-like proteins are present in mitochondria of bovine heart. PMID- 1857682 TI - Purification and characterization of a human leukemia cell-derived immunosuppressive factor. AB - A human leukemia cell-derived suppressor factor (LDSF) capable of suppressing in vitro proliferation and activation of normal human lymphocytes was purified from human leukemic HL-60 cells. LDSF is constitutively produced by the cells and was purified from serum free culture supernatant by a combination of ion-exchange chromatography, gel filtration and electrophoresis. Purified LDSF was determined to be a single chain protein with an apparent molecular mass of 66,000 daltons. LDSF was not cytolytic to lymphocytes, was heat stable at 70 degrees C, and did not have any effect on IL-2 or transferrin receptor expression. PMID- 1857683 TI - Purification of human placental trophoblast interferon by two-dimensional high performance liquid chromatography. AB - Human placental trophoblast challenged with Sendai virus induced IFNs mainly of the beta-type (75%) and relatively low levels of the alpha-type (25%). A two-step high performance liquid chromatographic procedure ("two-dimensional HPLC") has been developed for the complete purification of the placental trophoblast interferon beta (tro-IFN-beta) from serum-containing culture supernatant. The method involved a combination of high performance liquid affinity chromatography (HPLAC) on Cibacron Blue 3GA immobilized on an activated pressure stable macroporous synthetic polymer, 2-hydroxyethyl methacrylate vinyl sulphone (HEMA BIO 1000 VS), as the first dimension and reversed-phase high performance liquid chromatography (RP-HPLC) on Separon SGX C-18 as the second. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot experiments showed that the tro-IFN-beta was present as a 24 kDa protein. Densitometric scanning analysis of Coomassie-stained gel revealed the purity of the final preparation to be greater than 99%. The purified tro-IFN-beta had a specific activity of 1.03 x 10(8) IU/mg of protein and the overall recovery was 81% of the total IFN-beta activity in the crude preparation and 61% of the total IFN activity. PMID- 1857684 TI - An improved purification procedure for sulfite oxidase from bovine liver. AB - Sulfite oxidase (Sulfite:O2 oxidoreductase, EC 1.8.3.1) has been purified 2,440 fold from bovine liver. The procedure developed was used to isolate the enzyme from 1,000 g of liver and permitted the rapid isolation of enzyme with a very high specific activity (40,405 mU/mg). The enzyme preparations obtained have been characterized by electrophoretic and spectrophotometric analysis and the molecular mass and the Stokes radius of the enzyme have been determined. PMID- 1857685 TI - Purification and properties of alpha-aminoadipate aminotransferase from rat kidney. AB - Previous studies with rat kidney preparations indicated that alpha-aminoadipate aminotransferase (AadAT) and kynurenine aminotransferase (KAT) activities are associated with a single protein. However, recent studies from our laboratory demonstrated that AadAT and KAT activities belong to two different proteins. AadAT from rat kidney supernatant fraction was purified by affinity chromatography to electrophoretic homogeneity. This rapid and efficient procedure improved the yield and the degree of purification over previously published methods and separated AadAT from KAT. The molecular weight of the enzyme was estimated to be 89,000 by Sephadex G-200 gel filtration chromatography. SDS-PAGE indicated that the enzyme is composed of two apparently identical subunits. Absorption spectra and the kinetic properties of AadAT are reported. PMID- 1857686 TI - A simple preparative procedure to extract and purify protein G from group G streptococci. AB - A rapid method for the solubilization of the bacterial type III Fc binding protein, protein G, from a group G streptococcus is described. Treatment of intact bacteria with cyanogen bromide results in the solubilization of a homogeneous Mr approximately 50,000 protein which retains IgG and human serum albumin binding properties. The solubilized protein could be purified to homogeneity by molecular sieving chromatography and retained all of the functional properties of the native protein. PMID- 1857687 TI - [Bronchial clearance]. PMID- 1857688 TI - [Contribution to graphite dust lungs]. AB - This is a report on a male patient of 71 years of age who had been a graphite mill worker for about 14 years. Despite respiratory insufficiency he was rejected in 1985 as an applicant for being recognised as a victim of a professional disease, because the radiologically visible changes in the lung were only discrete. Perbronchial lung biopsy was performed in January 1990 as his dyspnoea increased. Histological examination revealed graphite dust disease of the lung. Asteroid bodies in multinucleated giant cells were an unusual finding. Energy dispersing x-ray microanalysis proved that the so-called graphite dust disease lung was actually a type of mixed dust pneumoconiosis. PMID- 1857689 TI - [Tension chylothorax following left-sided lung surgery]. AB - This is a report on 3 patients who presented with chylothoraces (chylopleurae) with haemodynamic effect subsequent to left-side lung surgery. This complication occurred twice after pneumonectomy and once after atypical resection with extirpation of a mediastinal lymph node. Clinical signs and symptoms appeared with all the patients between the 5th and 8th postoperative day, as a result of the haemodynamic effect of the chylothorax in the sense of volume loss combined with heart tamponade. In one patient there was additionally the pattern of signs and symptoms of an acute abdomen, which could be explained by a descended diaphragm with compression of the abdominal organs in case of an additionally present phrenicoparesis. One patient was at first treated conservatively after application of thoracic drainage, feeding being exclusively parenteral, and was finally operated on after 10 days, whereas the other two patients were primarily subjected to surgery. The surgical methods employed consisted of right side ductal ligature after Lampson, ductal ligature from the left thoracic side and direct closure of the chyle leakage. PMID- 1857690 TI - [Lung changes caused by Mycobacterium xenopi infection in a patient with bone marrow transplantation: problems in differential diagnosis]. AB - Pulmonary affections caused by atypical mycobacteria are an increasingly common problem particularly in patients with immune deficiency disorders. We here report a case of pulmonary infiltrates due to Mycobacterium xenopi in a patient after allogeneic bone marrow transplantation for acute myeloid leukemia in first complete remission and under immunosuppressive treatment with prednisolone and Cyclosporin A. While sputum cultures, serology as well as bronchial lavage and transbronchial biopsy remained inconclusive, diagnosis could only be established by open lung biopsy. We suggest that particularly in immunocompromised patients unclear pulmonary infiltrates require rapid and possibly invasive diagnostic procedures. PMID- 1857691 TI - [Intracellular metabolism in patients with insulin-dependent and non-insulin dependent diabetes mellitus]. AB - Slow infusion of neutral insulin causes in patients with insulin dependent and noninsulin dependent diabetes mellitus diverse changes in the levels of cAMP, cGMP and the cAMP/cGMP ratio in leukocytes in spite of one-type changes in the concentration of contrainsular hormones in the venous blood: in patients with noninsulin dependent DM a raised cAMP/cGMP factor was lowered whereas in patients with insulin dependent DM it was increased. The authors put forward for discussion the problem of the postreceptor mechanisms of tissue insulin resistance in noninsulin dependent DM and a possibility of the use of the above indices for differential diagnosis of DM types. PMID- 1857692 TI - [Medico-genetic counselling of the relatives of patients with type I diabetes mellitus]. AB - Population-genetic surveys show that for the relatives of patients with type I diabetes mellitus (the 1st degree of kinship) a risk of developing the same type of diabetes is 2-5%. Tables of repeated risk of developing diabetes mellitus (DM) of type I for persons with a different number of relatives affected by this type of DM were calculated on the basis of analysis of 2000 family histories of DM patients (a random sampling). A risk of developing this disease is in direct correlation with the number of sick and healthy relatives and their age. The presence of patients with type II DM in a family does not influence the risk of developing type I DM. Risk assessments are of prognostic rather than diagnostic value. The effectiveness of medico-genetic counselling can be increased with the help of various genetic markers, associated with type I DM. Risk assessment must lay the basis of a follow-up of persons with aggravated heredity by investigating immunological, hormonal and metabolic derangements in them. PMID- 1857693 TI - [Free fatty acid spectrum and rheological properties of erythrocytes in people with disturbed glucose tolerance and in patients with diabetes mellitus]. AB - The paper is devoted to a study of mechanisms of deterioration of blood rheological properties in disturbed carbohydrate metabolism in 17 patients with disorders in GTT and in 83 patients with diabetes mellitus (DM). The level of lipids, the spectrum of fatty acids (SFA) were determined in the blood plasma using gas chromatography by an original method, proposed by the authors for assessment of the rheological properties of erythrocytes (rotation viscosimetry of erythrocyte suspension in standard hematocrit of 45%). The concentrations of saturated and polyunsaturated acids in the blood plasma of persons with disturbed GTT and DM were increased, and the concentration of linoleic acid was lowered. More noticeable changes were observed in insulin dependent DM. A simultaneous increase in the viscosity of erythrocyte suspension at low rates of a shift in the DM group and change of the spectrum of fatty acids were revealed. Changes in the plasma SFA composition can be one of the causes of deteriorated rheological properties of erythrocytes. PMID- 1857694 TI - [Use of lysenyl-forte and methergoline in the therapy of hyperprolactinemic hypogonadism]. AB - The paper is concerned with a study of the effectiveness of lysenyl-forte (Hemapol, Czechoslovakia) and methergoline (Carlo Erba, Italy) for therapy of patients with different types of hyperprolactinemic hypogonadism. Altogether 49 patients were investigated, of them 33 received lysenyl-forte at a dose of 0.6 mg/day and 16-methergoline at a dose of 12 mg/day for 3 months. A degree of galactorrhea, a menstrual cycle and the blood level of prolactin were assessed before and after therapy. A prolactin inhibiting effect of both drugs comparable with that of bromocriptine was noted. However a clinical effect and good tolerance were more frequently observed in this sampling in lysenyl therapy. PMID- 1857696 TI - [Osteocalcin--a marker of bone metabolism and calcium regulating hormones in steroid osteoporosis]. AB - Altogether 15 patients with Itsenko-Cushing disease with moderate osteoporosis and 10 healthy persons were investigated. Calcium metabolism, calcium regulating hormones and osteocalcin were studied. Endogenous hypercorticoidism was characterized by a higher secretion of parathyroid hormone against a background of hypercalcemia. Positive correlation of these indices was revealed. In patients with Itsenko-Cushing disease the blood level of vitamin D was decreased as compared to that in the controls. A significant decrease in the blood level of osteocalcin was observed in patients with endogenous hypercorticoidism, there being close negative correlation between the level of osteocalcin and cortisol, and between osteocalcin and 17-hydroxycorticosteroid excretion with urine. A conclusion has been made that the excess of glucocorticosteroids suppresses osteoblast function, slows, down osteogenesis, disturbs the secretion of calcium regulating hormones and calcium metabolism enhancing resorption; this combined action of glucocorticoids causes rapid development of osteoporosis in endogenous hypercorticoidism. PMID- 1857695 TI - [Role of sex hormones in the development of atherogenic dyslipoproteinemia in boys of pubertal age]. AB - Interrelationships of hypercholesterolemia (HCS), hypertriglyceridemia (HTG) or hypo-alpha-cholesterolemia (hypo-CS HDL) and the blood levels of sex hormones were investigated in boys aged 14-15 to detect variations in the levels of sex hormones to define groups of adolescents at the highest risk of developing atherogenic dyslipoproteinemia (DLP). A conclusion has been made that HCS and hypo-CS HDL development is associated with changes in the blood levels of testosterone and estradiol, and a low blood level of T in HTG is of secondary origin with regard to the development of this type of DLP. PMID- 1857697 TI - [Use of computed tomography in the examination of patients with endocrine ophthalmopathy]. AB - Combined investigation of 29 patients with Basedow's disease, 5 patients with autoimmune thyroiditis, and 4 patients with mixed toxic goiter was carried out including computerized tomography (CT) of the orbits. The investigation of 10 patients was repeated 6 months after the first one. Signs of endocrine ophthalmopathy were detected in 28 patients with Basedow's disease and in 2 patients with autoimmune thyroiditis. Characteristic CT signs of retrobulbar tissue changes in endocrine ophthalmopathy were defined. The use of CT of the orbits was shown to improve early diagnosis of endocrine ophthalmopathies, to assess the time course of the disease and therapeutic efficacy. The authors proposed 3 variants of endocrine ophthalmopathy with regard to the involvement of the oculomotor muscles or retrobulbar fat tissue, revealed by CT. PMID- 1857699 TI - [Adequacy of hypoglycemic therapy in the treatment of diabetes mellitus]. PMID- 1857698 TI - [Epiphyseal-thyroid interrelations: effect of calcitonin on indole metabolism in health and in the presence of an excess of thyroid hormones]. AB - A new regularity was established in a study of epiphyseal thyroid interrelationships: the opposite effect of the thyroid hormones (thyroxin and calcitonin) on the formation of methoxyindoles (melatonin, 5-methoxytryptamine) in the epiphysis. Thyroxin was shown to stimulate and calcitonin to inhibit O methylation of serotonin in the pineal gland, and combined administration of both hormones levelled their action on one another. The inhibitory effect of calcitonin was more marked if a high basal level of melatonin was stimulated by preliminary administration of thyroxin. The authors assume that such a double control of the thyroid is "protective" for the epiphysis, preventing rapid depletion of reserves in case of excessive saturation of the body with thyroid hormones and maintaining its function in case of a sharp rise of the blood level of calcitonin. PMID- 1857700 TI - [Detection and prevention of the malfunction of an insulin dosing device under clinical conditions]. PMID- 1857701 TI - [Patient's role in maintaining stable compensation of diabetes mellitus]. PMID- 1857702 TI - [Transmission of "hormonal memory" of a unusual estrogen-binding protein during rat hepatocyte proliferation in the process of regeneration]. AB - The content of unusual estrogen-binding protein (UEBP), the level of DNA and common protein as well as the organ mass were studied over time during regeneration of the rat liver of intact males and gonadectomized males and females. In 21 days after partial hepatectomy of males with intact testes complete restoration of the UEBP content was observed simultaneously with restoration of the DNA and protein levels and the organ mass. There was no temporary decline of the UEBP content per DNA unit at the early stages of regeneration. The UEBP content in the liver grows during regeneration with the elevation of the DNA level not only in males with intact testes but also in preliminarily castrated males. Different UEBR programs were revcaled by the 21st day of liver regeneration in preliminarily gonadectomized animals: the androgen program of the elevated UEBP content in males, and the basal genetic program of the low level of UEBP expression in females. A conclusion has been made that the hormonal memory of a high UEBP content may be transferred to a new generation of hepatocytes in the absence of androgens. It has been assumed that androgens cause the real determination of masculinization of the EUBP content in liver cells. PMID- 1857703 TI - [Imprinting of metabolism of steroid hormones caused by the anabolic steroid drug methandrostenolone]. AB - An ability of the anabolic steroid drug methandrostenolone to induce irreversible metabolic changes of steroid hormones was studied. Neonatal administration of methandrostenolone to castrated rats was shown to cause the imprinting of metabolism of male type liver androgens. PMID- 1857704 TI - [Changes in the receptor binding of dexamethasone and insulin by blood cells in rats after hydrocortisone administration in early postnatal ontogenesis]. AB - A study was made of the effect of hydrocortisone, administered in early postnatal ontogenesis, on insulin and glucocorticoid reception in erythrocytes and mononuclear leukocytes. Hydrocortisone was administered to rat weanlings intraperitoneally at different ages of their life (5 days, 13, 15, 17 days, 1, 2 and 3 months). It has been assumed that extensive corticosteroid therapy resulting in prolonged imbalance of the level of the adrenocortical hormones and blood insulin, changes the receptor binding of these hormones on target cells as a result of a decrease in the hormone regulated receptor pool. PMID- 1857705 TI - [Role of hormones in maintaining the sex-differentiated level of estrogen receptors in rat liver cytosol]. AB - A study was made of the endocrine mechanisms of the formation and maintenance of a sex-differentiated level of estrogen receptors (ER) in rat liver cytosol. The administration of testosterone-propionate (TP) at a dose of 3 mg for 3 days was shown to cause a significant decrease in the concentration of ER in the liver of gonadectomized animals to the level in intact male rats. In a week after the discontinuation of TP, a complete restoration of the basal level of receptors was observed. Neonatal and prepubertal administration of TP to gonadectomized male rats at early stages of ontogenesis made no effect on the level of ER in the liver cytosol of these animals at the age of 12-14 weeks. The removal of the adrenal and thyroid glands produced no changes in the level of ER in the liver of rats of both sexes. Hypophysectomy in rats resulted even on the 1st day in a decrease in ER concentration in the liver of male and female animals to the same basal level which later on remained unchanged. Ectopic transplantation of a homologous hypophysis and human STH administration led to a significant rise of the level of ER in hypophysectomized animals. TP inhibited a stimulating effect of STH in rats with the removed hypophysis. PMID- 1857706 TI - [Effect of estrogens on the free fatty acid content and fatty acid-binding protein fractions in rabbit intestinal mucosa]. AB - A study was made of the effect of ovariectomy and administration of estradiol dipropionate on the level of estrogen receptors, low molecular protein fractions, incorporating fatty acid binding proteins (FABP), and free fatty acids (FFA) in the protein fractions of the cytosol of the intestinal mucosa of mature and immature female rabbits. The female rabbit upper intestinal mucosa was shown to possess cytoplasmic estrogen receptors and to have low metabolic activity of estradiol dehydrogenase (not being target tissue). Ovariectomy caused a decrease in the level of estrogen receptors, protein fractions, incorporating FABP, and FFA in them in enterocyte mucosa cytosol as compared to respective parameters in female rabbits in the pubertal and mature periods of their development. Estrogens were involved in the regulation of the level of intestinal fatty acid binding protein fractions and in ensuring physiological concentrations of absorbed fatty acids. PMID- 1857707 TI - [Morphological variants of thyroid autoimmune diseases]. AB - Analysis of the structural features of thyroid tissue, removed from 250 patients with Graves' disease, made it possible to define 3 morphological variants of Graves' disease differing not only by the type of pathological changes in the thyroid but also etiopathogenetically. One of the variants (parenchymatous type of the thyroid structure) may be of nonautoimmune origin; the second one is of primary autoimmune genesis (the classical variant, Basedow's disease, toxic goiter), and the third one is colloidal proliferating goiter with the autoimmune component (in approximately 50% of cases). Analysis of the structural features of thyroid tissue of 250 patients with Hashimoto's disease made it also possible to define its 3 morphological variants, differing both in a degree of expression of thyroid lymphoid infiltration and in the type of parenchymatous and stromal changes. PMID- 1857708 TI - [Surgical aspects of pancreas transplantation in patients with diabetes mellitus]. PMID- 1857710 TI - Linear free energy relationships in enzyme binding interactions studied by protein engineering. AB - Experiments on mutants of tyrosyl-tRNA synthetase have shown that there can be linear free energy relationships (LFERs) between changes in activation free energies and changes in binding energies when groups are deleted that bind to non reacting parts of the substrate (Fersht et al., 1986, 1987). It has now been proposed (Straub and Karplus, 1990) that such LFERs can occur for the mutation of hydrogen bonding groups only for the limiting examples of Bronsted beta of 0, 1 or infinity, and that fractional values of beta are not permissible. The reasoning behind this is that the energy of a hydrogen bond is not linear with distance and the (false) premise that an LFER requires that there is a linear relationship between bond energy and distance. We show from a simple model how LFERs can arise for binding interactions and how they can give fractional values of beta, in accord with experimental evidence. An LFER occurs between binding and catalysis when a set of interactions exists in which each member contributes to the binding energy of the transition state the same fraction of the binding energy it contributes to the products (both relative to the ground state). PMID- 1857709 TI - [Sex differences in drug metabolism in various endocrine diseases]. PMID- 1857711 TI - A novel method for the modelling of peptide ligands to their receptors. AB - A knowledge-based approach to the modelling of enzyme-peptide inhibitor complexes is described. Given the structure of an enzyme, and knowledge of its binding site, the method seeks to predict the binding geometry of a peptide ligand. This novel method involves using examples of side-chain packing derived from proteins of known three-dimensional structure to define possible packing arrangements of a peptide inhibitor group to its binding site. A suite of programs, GEMINI, was written and used to predict the packing of pairs of amino acid groups from three inhibitors complexed to their enzymes for which the X-ray structures were available. These included the Phe group of the inhibitor H142 bound to endothiapepsin, the Leu group of CLT complexed to thermolysin and the C-terminus of Gly-L-Tyr bound to carboxypeptidase A. A detailed comparison of the modelled and observed inhibitor coordinates was made. This approach may be extended to modelling other types of protein interactions. PMID- 1857712 TI - Modeling the three-dimensional structure of the monocyte chemo-attractant and activating protein MCAF/MCP-1 on the basis of the solution structure of interleukin-8. AB - A model of the three-dimensional structure of the monocyte chemo-attractant and activating protein MCAF/MCP-1 is presented. The model is predicted based on the previously determined solution structure of interleukin-8 (IL-8/NAP-1) [Clore, G.M., Appella, E., Yamada, M., Matsushima, K. and Gronenborn, A.M. (1990) Biochemistry 29, 1689-1696]. Both proteins belong to a superfamily of cytokine proteins involved in cell-specific chemotaxis, host defense and the inflammatory response. The amino acid sequence identity between the two proteins is 24%. It is shown that the regular secondary structure elements of the parent structure can be retained in the modeled structure, such that the backbone hydrogen bonding pattern is very similar in the two structures. The polypeptide backbone is superimposable with an atomic r.m.s. difference of 0.9 A and all side chains can be modeled by transferring the parent side chain conformation to the new structure. Thus, the deduced structure, like the parent one, is a dimer and consists of a six-stranded antiparallel beta-sheet, formed by two three-stranded Greek keys, one from each monomer, upon which lie two symmetry-related antiparallel alpha-helices, approximately 24 A long and separated by approximately 14 A. All amino acid sequence changes can be accommodated within the parent polypeptide framework without major rearrangements. This is borne out by the fact that the IL-8/NAP-1 and modeled MCAF/MCP-1 structures have similar non-bonding energies. These results strongly suggest that both proteins and all other members of the superfamily most likely have the same tertiary structure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1857714 TI - Recombinant hirudin: kinetic mechanism for the inhibition of human thrombin. AB - Recombinant hirudin variant-2(Lys47), was found to be a competitive inhibitor of human alpha-thrombin with respect to peptidyl p-nitroanilide substrates. These results contrast with those of Degryse and coworkers that suggest that recombinant hirudin variant-2(Lys47) inhibited thrombin by a noncompetitive mechanism [Degryse et al. (1989) Protein Engng, 2, 459-465]. gamma-Thrombin, which can arise from alpha-thrombin by autolysis, was shown to have an affinity for recombinant hirudin variant-2(Lys47) that was four orders of magnitude lower than that of alpha-thrombin. It was demonstrated that the apparent noncompetitive mechanism observed previously was probably caused by a contamination of the thrombin preparation by gamma-thrombin. Comparison of the inhibition of alpha thrombin by recombinant hirudins variant-2(Lys47) and variant-1, which differ from one another in eight out of 65 amino acids, indicated that the two variants have essentially the same kinetic parameters. PMID- 1857713 TI - A predicted three-dimensional structure of human cytochrome P450: implications for substrate specificity. AB - A three-dimensional structure for human cytochrome P450IA1 was predicted based on the crystal coordinates of cytochrome P450cam from Pseudomonas putida. As there was only 15% residue identity between the two enzymes, additional information was used to establish an accurate sequence alignment that is a prerequisite for model building. Twelve representative eukaryotic sequences were aligned and a net prediction of secondary structure was matched against the known alpha-helices and beta-sheets of P450cam. The cam secondary structure provided a fixed main-chain framework onto which loops of appropriate length from the human P450IA1 structure were added. The model-built structure of the human cytochrome conformed to the requirements for the segregation of polar and nonpolar residues between the core and the surface. The first 44 residues of human cytochrome P450 could not be built into the model and sequence analysis suggested that residues 1-26 formed a single membrane-spanning segment. Examination of the sequences of cytochrome P450s from distinct gene families suggested specific residues that could account for the differences in substrate specificity. A major substrate for P450IA1, 3 methyl-cholanthrene, was fitted into the proposed active site and this planar aromatic molecule could be accommodated into the available cavity. Residues that are likely to interact with the haem were identified. The sequence similarity between 59 eukaryotic enzymes was represented as a dendrogram that in general clustered according to gene family. Until a crystallographic structure is available, this model-building study identifies potential residues in cytochrome P450s important in the function of these enzymes and these residues are candidates for site-directed mutagenesis. PMID- 1857715 TI - Insertion of an elastase-binding loop into interleukin-1 beta. AB - The protease-binding sequence EAIPMSIPPE from alpha 1-antitrypsin has been inserted into the cytokine interleukin-1 beta, replacing residues 50-53. The resulting mutant protein was cleaved specifically at a single site by elastase and chymotrypsin, but not by trypsin. The cleavage by elastase was shown to be between Met and Ser of the inserted loop. In contrast, wild-type interleukin is not susceptible to cleavage by any of these enzymes. The mutant protein acts as an inhibitor of elastase, with a KI of approximately 30 microM. The wild type displays no such inhibitory activity. The overall structure of the mutant, as demonstrated by CD, appears to be indistinguishable from that of the wild type. These results indicate that the protease-binding region of alpha 1-antitrypsin can be recognized and is active even within the context of an entirely different protein structure. Given that interleukin-1 beta binds to, and is internalized by, many types of cells, this hybrid protein also demonstrates the feasibility of using interleukin-1 beta as a delivery system for useful therapeutic agents. PMID- 1857716 TI - Protein engineering of the propeptide of human factor IX. AB - Vitamin-K-dependent plasma proteins contain a highly conserved propeptide sequence located between the classical hydrophobic leader sequence and the N terminus of the mature protein. This acts as a recognition sequence for the vitamin-K-dependent carboxylase which catalyses the conversion of specific glutamate residues to gamma-carboxyglutamate (Gla) residues in the adjacent Gla domain. Protein engineering of the 18 residue propeptide from human factor IX has highlighted the importance of residues -16Phe and -10Ala with respect to carboxylase recognition. In addition, studies of haemophilia B patients have shown that C-terminal propeptide residues -4Arg and -1Arg are required for proteolysis of the propeptide from the mature protein. To extend these previous studies we have introduced two novel mutations into the propeptide of human factor IX at positions -17(Val----Asp) and -6(Leu----AsP), and studied the effect of these changes on gamma-carboxylation and proteolytic processing. Both mutations reduce the expression of a calcium-dependent epitope in the Gla domain; however, only -6Leu----Asp shows reduced binding to barium sulphate. In addition, this latter mutation prevents proteolytic processing of the propeptide. These data support the current hypothesis that the propeptide contains two recognition elements: one for carboxylase recognition located towards the N-terminus, and one for propeptidase recognition located near the C-terminus. PMID- 1857717 TI - Temperature-sensitive production of rabbit muscle glycogen phosphorylase in Escherichia coli. AB - In order to understand how allosteric switches regulate both the catalytic activity and molecular interactions of glycogen phosphorylase, it is necessary to design and analyze variant proteins that test hypotheses about the structural details of the allosteric mechanism. Essential to such an investigation is the ability to obtain large amounts of variant proteins. We developed a system for obtaining milligram amounts (greater than 20 mg/l) of rabbit muscle phosphorylase from bacteria. Phosphorylase aggregates as inactive protein when a strong bacterial promoter is used under full inducing conditions and normal growth conditions. However, when the growth temperature of bacteria expressing phosphorylase is reduced to 22 degrees C we obtain active muscle phosphorylase. The degree to which the induced expression of phosphorylase protein is temperature sensitive depends on the strain of bacteria used. New assay and purification methods were developed to allow rapid purification of engineered phosphorylase proteins from bacterial cultures. The rabbit muscle phosphorylase obtained from the bacterial expression system is enzymatically identical to the enzyme purified from rabbit muscle. The expressed protein crystallizes in the same conditions used for growing crystals of protein from rabbit muscle and the crystal form is isomorphous. Rabbit muscle phosphorylase is one of the largest oligomeric mammalian enzymes successfully expressed in Escherichia coli. Our results indicate that optimization of a combination of growth and induction conditions will be important in the expression of other heterologous proteins in bacteria. PMID- 1857719 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 1857718 TI - Improving the prediction of secondary structure of 'TIM-barrel' enzymes. AB - The information contained in aligned sets of homologous protein sequences should improve the score of secondary structure prediction. Seven different enzymes having the (beta/alpha)8 or TIM-barrel fold were used to optimize the prediction with regard to this class of enzymes. The alpha-helix, beta-strand and loop propensities of the Garnier-Osguthorpe-Robson method were averaged at aligned residue positions, leading to a significant improvement over the average score obtained from single sequences. The increased accuracy correlates with the average sequence variability of the aligned set. Further improvements were obtained by using the following averaged properties as weights for the averaged state propensities: amphipathic moment and alpha-helix; hydropathy and beta strand; chain flexibility and loop. The clustering of conserved residues at the C terminal ends of the beta-strands was used as an additional positive weight for beta-strand propensity and increased the prediction of otherwise unpredicted beta strands decisively. The automatic weighted prediction method identifies greater than 95% of the secondary structure elements of the set of seven TIM-barrel enzymes. PMID- 1857720 TI - Triple signal transduction model for the mechanism of PGE2 actions in rabbit cortical collecting duct. PMID- 1857721 TI - Endothelin-1 stimulates prostaglandin F2 alpha release from human endometrium. AB - Despite a key role in the pathogenesis of menorrhagia, the factors controlling the uterine vascular bed are poorly understood. This study has assessed the effects of the potent vasoconstrictor endothelin (ET)-1 on prostaglandin (PG) release from human endometrial explants in short-term culture. There was no significant difference between the production of PGF2 alpha in proliferative and secretory tissue (1709 and 2434 pg/mg/h--median values, range 70,3745 and 219,6700 pg/mg/h). Less PGE was released than PGF2 alpha, and the amount did not vary with the phase of the menstrual cycle (308 and 296 pg/mg/h (range 65,387 and 105,429) for proliferative and secretory tissue). ET-1 (10 and 100 nM) and arachidonic acid (AA, 30 microM), stimulated PGF2 alpha release from proliferative, but not secretory endometrium, by 78%, 86% (P less than 0.01) and 80% respectively, compared with control tissue. No effect was seen on PGE release. ET-1 may play a role in the local control of the endometrial vascular bed either directly, or via the release of PGF2 alpha. PMID- 1857722 TI - Differences between in vivo and in vitro production of eicosanoids following long term dietary fish oil supplementation in the rat. AB - The effects of different lipid supplements on endogenous and exogenous production of eicosanoids were investigated in the rat following a 12-month pre-feeding period. The urinary excretion of tetranorprostanemonoic (TPM) and tetranorprostanedioic (TPD) acids was measured as an index of endogenous production whilst myocardial release of PGI2 and TXA2 was estimated under in vitro conditions. Compared to the reference group, n-3 PUFA rich tuna fish oil (TFO) fed rats displayed a near doubling of endogenous (TPM + TPD) synthesis; however, myocardial production was reduced by 32% (PGI2) and 55% (TXA2). Sheep fat supplementation also caused a 62% rise in urinary tetranor metabolites but in contrast to TFO feeding, myocardial production in vitro also showed a significant increase (P less than 0.05). Considerable changes in PUFA profile of plasma, heart and kidney occurred as a result of dietary lipid treatment and in addition a high tissue specificity was also noted with regard to the incorporation and conversion of dietary n-3 PUFA. For example, the heart showed a low EPA (1.2%) and high DHA (28.0%), whereas their proportions in the kidney were near equal (6 7%). As only the TFO diet exerted a significant effect on the proportion of AA, the changes in eicosanoid production cannot be fully explained on the basis of precursor/inhibitor availability. The results probably reflect the complex interactions between fatty acid substrates, release mechanisms and biosynthetic enzymes. PMID- 1857723 TI - Prostaglandin production by amnion and decidual cells in response to bacterial products. AB - Media from bacterial cultures have been tested for actions on prostaglandin biosynthesis by human amnion and decidual cells. The bacterial species, which are commonly associated with intrauterine infections, were Group B streptococcus, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis, Gardnerella vaginalis, Neisseria gonorrhea, Mycoplasma hominis and Ureaplasma urealyticum. Overall, low doses of bacterial products were stimulatory of amnion prostaglandin production, whereas high doses were inhibitory. A similar pattern of results was obtained for effects on decidual prostaglandin production, although stimulatory actions at low doses were less pronounced. In all experiments interleukin 1 beta consistently induced a stimulation of prostaglandin production that greatly exceeded that caused by any bacterial product. It is possible that the inhibitory action of high doses of bacterial products on prostaglandin biosynthesis may contribute to the poor course of labor experienced by women with chorioamnionitis. Furthermore, these data lend credence to the view that the host response to infection (i.e. cytokine secretion) is the major mediator of subsequent preterm labor. PMID- 1857724 TI - Down-regulation of prostaglandin F2 alpha receptors in rat liver during chronic endotoxemia. AB - Prostaglandin (PG) F2 alpha binding parameters were measured in purified plasma membrane preparations isolated from livers of chronically endotoxin-(ET) treated rats and corresponding controls. Two classes of binding sites were detected in both groups: high affinity, low capacity, with a KD of 44.4 +/- 8.8 nM for saline and 28.6 +/- 11.3 nM for ET-treated rats (n = 5 for both, p greater than 0.05) and low affinity, high capacity with a KD of 1.12 +/- 0.49 microM for saline- and 1.24 +/- 0.43 microM for ET-treated rats (p greater than 0.05). Bmax values for high affinity sites were 1.01 +/- 0.18 fmol.mg-1 protein for saline- and 1.02 +/- 0.54 (same units) for ET-treated rats (p greater than 0.05). There was a significant difference (p less than 0.01) between the Bmax values for low affinity sites in saline- (675 +/- 332 fmol.mg-1 protein) and ET-treated rats (12 +/- 1, same units). This decrease in the amount of PGF2 alpha low affinity high capacity binding sites may underlie the depression of the PGF2 alpha stimulatory effect on hepatic gluconeogenesis induced by non-lethal, chronic ET treatment of rats, recently described by us (9). PMID- 1857725 TI - Effect of dietary calcium on renal prostaglandins. AB - The present study was designed to clarify the possible role of renal prostaglandins (PGs) on blood pressure (BP) regulation during calcium (Ca) restriction or supplementation. Twelve normotensive women with a mean age of 21.2 years participated in the study. After 1 week of normal Ca intake (mean +/- SE, 536 +/- 2 mg/day), a low-Ca diet (163 +/- 1 mg/day) was given for a further 1 week. Additional asparagine Ca (3 g as Ca/day) was also given to half of the subjects. BP, heart rate, and serum total and ionized Ca concentrations were measured at the end of each period. Levels of Ca, sodium, PGE2, 6-keto-PGF1 alpha and thromboxane (TX) B2 excreted into urine were also determined. The plasma level of ionized Ca was significantly increased without any change in total Ca in both groups. Low and high Ca intake decreased and increased urinary Ca excretion by 28% and 56%, respectively. BP was not altered after Ca deprivation or loading. However, urinary PGE2 excretion was significantly augmented from 668.9 +/- 68.1 to 959.7 +/- 183.1 ng/day by Ca loading, whereas Ca deprivation decreased PGE2 excretion (695.4 +/- 108.1 to 513.2 +/- 55.2 ng/day). No changes were observed in 6-keto-PGF1 alpha or TXB2 urinary excretion. These results suggest that renal PGE2 synthesis is stimulated or decreased by 1-week Ca loading or deprivation, indicating a possible antihypertensive role of renal PGE2 during high-Ca intake in hypertensives. PMID- 1857726 TI - [Experimental design and interpretation of studies of radioligand binding]. PMID- 1857727 TI - Disposition of lypophilized (methylmethacrylate-14C, 2-hydroxyethylmethacrylate, butylacrylate) nanoparticles in rats and their effect on zoxazolamine paralysis time. AB - The fate of lyophilized (methylmethacrylate-14C, 2-hydroxyethylmethacrylate, butylacrylate) nanoparticles was studied in male Wistar rats after p.o. administration. It was found that at least 4% of the dose of 14C was absorbed from the gastrointestinal tract after a single dose with these nanoparticles. Some radioactivity (less than 0.15% of dose) was found 7 d after administration in lung, spleen and liver. As expected excretion of the label was predominated via the feces. Ten d of p.o. treatment of rats with lyophilized nanoparticles (1 g/kg of body weight) was shown to prolong significantly zoxazolamine paralysis time. This result suggests that lyophilized nanoparticles decreased elimination of zoxazolamine. PMID- 1857728 TI - [Bioavailability of griseofulvin in the form of liposomes]. AB - Liposomes containing griseofulvin have been prepared by shaking method. Lecithin and cholesterol were used to compose phospholipid bilayer of liposomes. The suspension of liposomes in 0.9% sodium chloride and the suspension of griseofulvin in 0.25% iostonic methylcellulose solution were used in the comparative study in vivo. Both suspensions were administered intragastricly to rats. Parameters of bioavailability have been found on the basis of the changes in griseofulvin plasma concentrations versus time. Intragastric administration of griseofulvin in liposomes suspension demonstrates ca. 40% higher Cmax and AUC when compared to these of griseofulvin suspension which indicates a better bioavailability. PMID- 1857729 TI - In vitro inhalation behaviour and therapeutical response of salbutamol particles administered from two metered dose aerosols. AB - In this study the particle size, as well as the in vitro deposition and the immediate bronchodilating effect on asthmatic patients, of two salbutamol inhalation aerosol preparations (Ventoline, Glaxo, UK, and salbutamol inhalation aerosol, Orion Pharmaceutica, Finland) were compared. The in vitro deposition study was performed using the modified Sierra Andersen cascade impactor. The bronchodilating effect of inhaled aerosol doses were monitored by measuring peak expiratory flow (PEF) values. In the clinical study, the pulse and blood pressure of the patients, as well as the side effects, were also recorded. Due to the anatomy and physiology of human lungs, the accepted optimum size for inhaled drug particles is under 5 microns, and preferably under 2 microns. Over 95% of the drug particles in both aerosol preparations were under 5 microns. 30% of the salbutamol particles in the Ventoline inhalation aerosol were under 2 microns, whereas in Orion salbutamol aerosol 14% of the drug particles were under 2 microns. Respectively 23% of Ventoline and 19% of the Orion salbutamol preparation penetrated into the therapeutically most significant imitated alveolar stages of the modified cascade impactor. Both salbutamol aerosols showed a clear clinical efficacy in the bronchodilating test. In addition, no significant differences existed in the bronchodilating effect of these inhalation aerosols. In conclusion, although there seemed to be a slight difference in the particle size distribution and in the in vitro inhalation behaviour, this variation did not have any effect on the clinical response. PMID- 1857731 TI - [The action of trypsin and zymosan on the respiration of cultivated endothelial cells]. AB - Trypsin and Zymosan induce an increase in respiration activity of cultivated endothelial cells. These effects are not due to the production of oxygen radicals. The effect of trypsin will be explained by interfering with the cellular homeostasis of calcium. The stimulated respiration after incubation with zymosan may be connected with the increased phagocytosis. PMID- 1857730 TI - Influence of melanoma B16 on the pharmacokinetics of mitoguazone in mice. AB - In this study, the influence of different stages and transplantation routes of the experimentally widely used solid tumor melanoma B16 on the pharmacokinetics of the antineoplastic agent mitoguazone was investigated in B6D2F1 mice. It could be shown that changes of the pharmacokinetic parameters as well as the distribution pattern of this drug were clearly influenced and dependent on the tumor stage but not by the tumor inoculation route. Advanced melanoma (d16) led to a sharp decrease in the terminal elimination half-life as well as to decreased spleen levels and increased initial liver concentrations of the drug. With respect to the results obtained in leukemia P388-bearing mice it can be concluded that the tumor stage as well as the tumor model are to be considered as important factors in which way and to which extent a tumor may alter the pharmacokinetics of antineoplastic agents. PMID- 1857732 TI - [Scientific relationship between German and Hungarian pharmacy]. PMID- 1857733 TI - Some new benzimidazolyl-N, N-aminomethyl and 1-aminomethyl derivatives of pharmacological interest. PMID- 1857735 TI - [The biochemical basis of pharmaceutical chemistry. 9. The effect of structure on biopharmaceutic/pharmacokinetic behavior]. PMID- 1857734 TI - In vitro and in vivo comparison of arginine- and benzamidine-derived highly potent synthetic thrombin inhibitors. PMID- 1857736 TI - [Parenteral depot drug forms with a base of biodegradable polymers]. PMID- 1857738 TI - Electronic states of the indole-acrylamide molecular pair. AB - A model is suggested for tryptophan fluorescence quenching by acrylamide based on the prediction that acrylamide can absorb a photon from the excited indole moiety and then dissipate the optical energy into a sink of fast exchanging conformations. Semiempirical electronic structure calculations of the indole acrylamide pair indicate little actual intermolecular orbital mixing at van der Waals contact distances. However, the two lowest singlet transitions of the molecular pair, assigned to the acrylamide (pi *)----n(O) line and to the indole 1Lb----1A1 line, respectively, vary significantly in energies and in transition and excited state moments with the geometry of interaction between the two entities. The distribution of optimal quenching coordinations depends separately on the benzene and pyrrole portions and has a distinctly non-spherical shape at these distances. PMID- 1857737 TI - Dietary histidine increases mouse skin urocanic acid levels and enhances UVB induced immune suppression of contact hypersensitivity. AB - Urocanic Acid (UCA) exists in mammalian skin primarily as the trans isomer and is photoisomerized to cis UCA upon UVB absorption. Our previous studies indicated that the photoisomerization of UCA is the initiating event in UBV-induced suppression of cell-mediated immunity (tUCA----cUCA----immune suppression). The purpose of this study was to verify the role of UCA in UV-induced immune suppression of contact hypersensitivity (CHS) in BALB/c mice. Since UCA is a metabolite of the amino acid L-histidine, we reasoned that increased dietary levels of histidine should raise skin tUCA levels. If skin tUCA is the UVB photoreceptor for immune suppression, this increase should enhance UV-induced suppression of CHS. HPLC analysis of skin from BALB/c mice given a histidine-rich diet (10%) showed that the total amount of UCA is significantly higher in these animals than in mice fed a normal diet. Further, levels of suppression of CHS of 3% and 49% in control fed mice, induced by 4.8 and 7.2 kJ/m2 UVB were significantly increased to 21% and 71% respectively in histidine-fed animals at these same UVB doses. These findings provide additional support for the UCA model for immune suppression, and provide the first evidence that UV-induced immune suppression can be enhanced by a dietary component, L-histidine. PMID- 1857739 TI - Species differences in response to photohemolytic agents. AB - Species differences in red blood cell susceptibility to the photohemolytic agents chlorpromazine, menadione and tetracycline were examined in mouse, rat, dog, and human blood. Menadione and tetracycline (25 microM) hemolyzed mouse but not dog, rat, or human red blood cells (RBC) when irradiated with UV light but not in the dark. Chlorpromazine (25 microM) produced a photohemolytic response in all four species with mouse and rat RBC lysing fastest followed by human then dog cells. Investigations into the nature of these species differences suggested that the size of mouse RBC may contribute to its high sensitivity to photohemolytic agents. An investigation of the effect of UV light on key antioxidant enzymes revealed species differences in enzyme inactivation. These data suggest that mouse RBC may be particularly vulnerable to phototoxic agents, especially those compounds which produce active oxygen species and, therefore, may prove more useful than human RBC as a model for predicting phototoxic potential of some chemical entities. PMID- 1857740 TI - alpha-Terthienyl photosensitizes damage to pBR322 DNA. AB - alpha-Terthienyl photosensitizes single strand breaks in pBR322 DNA. Almost identical results were observed under oxygen and under argon. In the presence of oxygen, this DNA nicking was enhanced by histidine and was not affected by superoxide dismutase, catalase, or the antioxidant BHT. Although chemical damage to DNA treated with alpha-terthienyl plus near-UV was clearly demonstrated in vitro, transformation in E. coli with this damaged pBR322 DNA still took place. Likewise, Haemophilus influenzae DNA transforming activity was not significantly decreased by photosensitization with alpha-terthienyl. PMID- 1857741 TI - Photophysical and photobiological properties of diporphyrin ethers. AB - Spectral properties of several diporphyrin ethers were assessed in different solvents and after accumulation by leukemia L1210 cells in vitro. To facilitate studies in a variety of solvents, both tetramethylesters of the diporphyrin ethers and free acids were employed. For comparison, studies on the corresponding porphyrin monomers were also carried out. The joining of two porphyrins by an ether linkage had several consequences. We observed a blue shift in the Soret band of the ethers, but not of the corresponding simple porphyrins, in protic solvents. This phenomenon is likely related to ether aggregation under conditions which promote H-bonding. The presence of an ether linkage was associated with enhanced fluorescence at 630-640 nm and decreased fluorescence lifetimes and yields, especially in protic solvents. The ether linkage was unaffected by intracellular enzymes, but porphyrin esters were readily hydrolyzed upon accumulation by L1210 cells. The joining of two hematoporphyrin molecules by an ether linkage promoted dye accumulation by L1210 cells. In contrast, accumulation of mesoporphyrin and protoporphyrin was thereby retarded. PMID- 1857742 TI - Photosensitization by synthetic diporphyrins and dichlorins in vivo and in vitro. AB - A group of polycarboxylic diporphyrins, two dichlorins and a porphyrin-chlorine dimer, with rings linked by methylene groups, were examined to help identify structures which can mediate photodynamic tumor eradication in vivo. Among the features sought were short persistence of normal tissue photosensitization and substantial absorbance at wavelengths longer than 630 nm. Both objectives were achieved, with pertinent structure-activity relationships partly characterized. The relative hydrophobicity of the different sensitizers was an important determinant of their accumulation in cell culture, but not of in vivo effectiveness. These compounds showed affinity for protein and high-density lipoprotein components of serum. Their distribution may be mediated by a different mechanism than that which occurs with more hydrophobic sensitizers like hematoporphyrin derivative which have greater affinity for low-density lipoproteins and less for protein components of serum, as compared with the products examined in this study. PMID- 1857743 TI - Photosensitized lipid peroxidation and enzyme inactivation by membrane-bound merocyanine 540: reaction mechanisms in the absence and presence of ascorbate. AB - The lipophilic photosensitizing dye merocyanine 540 (MC540) is being studied intensively as an antitumor and antiviral agent. Since plasma membranes are believed to be the principal cellular targets of MC540-mediated photodamage, we have studied membrane damage in a well characterized test system, the human erythrocyte ghost. When irradiated with white light, MC540-sensitized ghosts accumulated lipid hydroperoxides (LOOHs derived from phospholipids and cholesterol) at a rate dependent on initial dye concentration. Neither desferrioxamine nor butylated hydroxytoluene inhibited LOOH formation, suggesting that Type I (iron-mediated free radical) chemistry is not important. By contrast, azide inhibited the reaction in a dose-dependent fashion, implicating a Type II (singlet oxygen, 1O2) mechanism. Stern-Volmer analysis of the data gave a 1O2 quenching constant approximately 50 times lower than that determined for an extramembranous target, lactate dehydrogenase (the latter value agreeing with literature values). This suggests that 1O2 reacts primarily at its membrane sites of origin and that azide has limited access to these sites. Using [14C]cholesterol-labeled membranes and HPLC with radiodetection, we identified 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide as the major cholesterol photoproduct, thereby confirming 1O2 intermediacy. Irradiation of MC540 sensitized membranes in the presence of added iron and ascorbate resulted in a large burst of lipid peroxidation, as shown by thiobarbituric acid reactivity and appearance of 7-hydroperoxycholesterol and 7-hydroxycholesterol as major oxidation products. Amplification of MC540-initiated lipid peroxidation by iron/ascorbate (attributed to light-independent reduction of nascent photoperoxides, with ensuing free radical chain reactions) could prove useful in augmenting MC540's phototherapeutic effects. PMID- 1857744 TI - Photodynamic action of merocyanine 540 in artificial bilayers and natural membranes: action spectra and quantum yields. AB - The action spectra and quantum yields for singlet oxygen (1O2) generation by merocyanine 540 (MC540) in liposomes and isolated erythrocyte membranes were obtained using electron spin resonance techniques. Oxygen consumption was measured by spin label oximetry in the presence of histidine for fully-saturated dimyristoylphosphatidylcholine vesicles, mono-unsaturated 1-palmitoyl-2 oleoylphosphatidylcholine vesicles and erythrocyte membranes. The quantum yield for the photogeneration of 1O2 by membrane-bound MC540 in aqueous buffer was determined to be 0.065 +/- 0.005, which is approx. 1/10 of the value determined for Rose Bengal under similar conditions. Using unilamellar liposomes and isolated erythrocyte membranes containing MC540 at different monomer/dimer ratios, we have observed that the action spectra of 1O2 generation closely overlap the absorption spectra of the monomeric dye in these systems. It is likely that factors which affect the monomer-dimer equilibrium of MC540 will influence the production of 1O2. These findings have important implications for the phototherapeutic efficacy of MC540. PMID- 1857745 TI - Tanning salon exposure suppression of DNA repair capacity and mitogen-induced DNA synthesis. AB - Mitogen responsiveness and the capacity to repair genetic damage were measured in lymphocytes collected from young, healthy, adult Caucasians immediately before exposure in commercial tanning salons and again 24 h after exposure. For every individual studied, tanning exposure produced significant inhibition of phytohemagglutinin-induced mitogenesis or of the ability to repair DNA lesions by unscheduled DNA synthesis. The results imply that such exposure could: (1) pose a significant hazard for individuals who are already immunosuppressed (e.g. cancer patients, AIDS patients or carriers of latent HIV) and (2) increase the carcinogenic effects of environmental mutagens. PMID- 1857746 TI - Inhibitory effect of 8-methoxypsoralen plus ultraviolet-A on interleukin-1 production by murine keratinocytes. AB - We report the effects of 8-methoxypsoralen (8-MOP) plus ultraviolet-A (UV-A) irradiation on interleukin-1 (IL-1) production by murine epidermal keratinocytes, correlating its effect on IL-1 with cell viability, DNA synthesis, and 8-MOP-DNA photoadduct formation. Freshly isolated murine keratinocytes were treated with various doses of 8-MOP (5-100 ng/mL; incubation time, 30 min) plus 1 J/cm2 UV-A and cultured for 1-3 days. The IL-1/epidermal cell-derived thymocyte-activating factor (ETAF) activity in both supernatant and cell extract was reduced proportionately with increasing doses of 8-MOP/UV-A. Interleukin-1 inhibitors induced by 8-MOP plus UV-A were not detected in either supernatant or cell extract. A clear reduction of the IL-1 production was induced by the treatment as low as 15 ng/mL 8-MOP plus 1 J/cm2 UV-A, which led to the formation of 0.52 8-MOP photoadducts per million DNa bases and affected neither cell viability nor DNA synthesis of the treated cells. Cells treated with 100 ng/mL 8-MOP and 1 J/cm2 UV A exhibited 57% suppression of IL-1 production in both 2- and 3-day culture samples. This treatment resulted in the formation of 3.8 photoadducts per million bases as well as significant abrogation of DNA synthesis although cell viability was unchanged. These observations provide some insights into the phototoxicity mechanisms of 8-MOP and the effect of PUVA therapy on the cytokine regulation in keratinocytes. PMID- 1857747 TI - Are the effects of light on phase and period of the Gonyaulax clock mediated by different pathways? AB - The effects of different wavelengths of light on period, phase shifting, entrainment and after-effects of the circadian clock of the motile marine dinoflagellate Gonyaulax polyedra are described. Phase shifting and entrainment by light can be explained by the action of a single blue sensitive light input pathway. However, tonic effects of light on the period under free-running conditions, and also after-effects on period resulting from single 4 h light exposures, appear to involve two input pathways with different absorption and temperature characteristics. These results suggest different mechanisms for the control of phase and period of the circadian clock. PMID- 1857748 TI - Fluorescence energy transfer between dimethyldiazaperopyrenium dication and ethidium intercalated in poly d(A-T). AB - Dimethyldiazaperopyrenium is one of the largest known DNA intercalators. Fluorescence energy transfer occurred between dimethyldiazaperopyrenium (donor) and ethidium (acceptor) when these dyes were bound to a double-stranded polynucleotide such as poly d(A-T). The addition of increasing amounts of ethidium bromide led to a marked shortening of the fluorescence lifetime of the donor, whereas the excited state of the acceptor was progressively populated via energy transfer from the donor. Critical Forster distance between these two chromophores was calculated to be 3.8 nm. The observed transfer efficiency was lower than that calculated on the basis of this critical distance and a statistical distribution of bound drugs. These results are discussed taking into account the conformational change induced by intercalation of dimethyldiazaperopyrenium in the double-stranded polynucleotide. PMID- 1857749 TI - Do pyrimidine dimer yields correlate with erythema induction in human skin irradiated in situ with ultraviolet light (275-365 nm)? AB - Ultraviolet radiation produces erythema in human skin, and damages the DNA of living cells in skin. Previous work showed that broad-band UV-B (290-320 nm) radiation produced higher levels of cyclobutyl pyrimidine dimers in DNA of individuals with high UV-B sensitivity (low minimal erythema dose) than in subjects of low UV-B sensitivity [Freeman et al. (1986) J. Invest. Dermatol., 86, 34-36]. We examined the relationship between erythema induction and dimer yields in DNA of human skin irradiated in situ with narrow band radiation spanning the wavelength range 275-365 nm. We find that, in general, higher dimer yields are produced per incident photon in volunteers with higher susceptibility to erythema induced by radiation of the same wavelength. PMID- 1857750 TI - The bacteriophage resistance plasmid pTR2030 forms high-molecular-weight multimers in lactococci. AB - Lactococcus lactis ME2 can transfer a 46-kb plasmid, pTR2030, which encodes abortive phage infection (Hsp) and restriction/modification (R/M) activities. pTR2030 can be detected as a monomeric plasmid in transconjugants at low copy number, but not in ME2. pTR2030-specific probes were cloned and used to determine the location of the element in ME2. No homology was observed between these pTR2030-specific probes and the CsCl-purified plasmid content of ME2. However, probes specific for pTR2030 hybridized strongly to a high-molecular-weight moiety, and not to chromosomal DNA, in total DNA isolated by a gentle lysis procedure. The absence of junction fragments indicates that pTR2030 forms high molecular-weight multimers in lactococci. A phage-sensitive derivative of ME2, L. lactis N1, is cured of pTR2030 and no longer possesses the high-molecular-weight species. When pTR2030 was reintroduced to N1 via conjugation, an ME2-like phage insensitive phenotype was restored. pTR2030 could remain as a detectable monomeric plasmid in the N1 transconjugants or could revert to the high-molecular weight structure. PMID- 1857751 TI - Characterization and sequence analysis of a small plasmid from Bacillus thuringiensis var. kurstaki strain HD1-DIPEL. AB - The complete nucleotide sequence of a small (2.055 kb) plasmid pHD2 from Bacillus thuringiensis var. kurstaki strain HD1-DIPEL was obtained. The sequence encoded two open reading frames (ORFs) which corresponded to polypeptides of Mr 26,447 and 9122. Comparison of the sequence with those obtained for other plasmids from Gram-positive organisms suggested that pHD2 may belong to the extensive and highly interrelated family of plasmids exhibiting replication via a ssDNA intermediate: a putative nick site was proposed on the basis of sequence homology and one ORF exhibited distant homology with the site-specific topoisomerases encoded by the pT181 family of staphylococcal plasmids, while the other ORF exhibited considerable similarity to a small polypeptide (RepA) encoded by plasmid pLS1. Constructs consisting of pHD2, pBR322, and the chloramphenicol resistance gene from pC194 were capable of stable maintenance in B. thuringiensis var. israelensis, but were subject to apparently specific deletions in the heterologous host. The same constructs could not be established in Bacillus subtilis. PMID- 1857752 TI - Plasmid Co1IB contains an ssi signal close to the replication origin. AB - Taking advantage of the plaque morphology method, we identified a single-strand initiation (ssi) signal in plasmid pSM32, a mini-Co1Ib plasmid. This ssi signal was situated in the 350-nt HaeIII segment of the 1.8-kb S7 fragment, and located nearly 400 nt downstream of the origin of DNA replication. Introduction of the ssi signal into a mutant of filamentous phage M13 lacking oric resulted in restoration of phage growth and RFI DNA synthesis. Interestingly, DNA homology studies showed that the nucleotide sequence of the ssi signal was extremely homologous with that of the "G4-type" ssi signal in plasmid R100. PMID- 1857753 TI - Isolation and properties of temperature-sensitive mutants of the trfA gene of the broad host range plasmid RK2. AB - Two small plasmid RK2 derivatives, pSV6 and pSV16, were constructed and used for the isolation and characterization of trfA mutants temperature-sensitive (ts) for replication in Escherichia coli. Four of the mutants were examined for their ability to initiate replication from the RK2 replication origin in E. coli when present in cis with respect to the origin and in trans when present on a multicopy pBR322 replicon. Each of the mutant trfA genes exhibited temperature sensitivity in supporting replication from the RK2 origin when present in cis, and the lowest nonpermissive temperature varied depending on the mutant. When the mutant trfA genes were present on the multicopy replicon (in trans), three of the four mutant genes could support replication of the RK2-oriV plasmid pSV16 at all temperatures tested. However, with the exception of one of the mutants, the activity was reduced when compared to wild-type. The increased activity in trans possibly is the result of the increased cellular level of the TrfA protein when compared with the in cis situation where the mutant trfA gene is at a much lower copy-number. Two of the mutants also were tested in cis for temperature sensitivity in Pseudomonas aeruginosa. One of the mutants did not exhibit temperature sensitivity under the conditions employed. The second mutant showed some temperature sensitivity but the nonpermissive temperature pattern was different than that found in E. coli. PMID- 1857754 TI - Construction and characterization of a Mycobacterium-Escherichia coli shuttle vector. AB - We have constructed a set of novel Mycobacterium-Escherichia coli shuttle vectors using either a kanamycin- or hygromycin-resistance gene and the replication region from a Corynebacterium plasmid. Important features of these new vectors (pEP2 and pEP3) are that they are small, contain multiple cloning sites, and replicate to high copy number in various Mycobacterium species and E. coli. These vectors are unusual in that plasmid replication in gram-negative and gram positive bacteria appears to be controlled from a single region. These plasmids will be useful for the genetic analysis of Mycobacterium and gene expression in this genus, particularly Mycobacterium bovis BCG. PMID- 1857755 TI - The 2-micron plasmid as a nonselectable, stable, high copy number yeast vector. AB - The endogenous 2-microns plasmid of Saccharomyces cerevisiae has been used extensively for the construction of yeast cloning and expression plasmids because it is a native yeast plasmid that is able to be maintained stably in cells at high copy number. Almost invariably, these plasmid constructs, containing some or all 2-microns sequences, exhibit copy number levels lower than 2-microns and are maintained stably only under selective conditions. We were interested in determining if there was a means by which 2-microns could be utilized for vector construction, without forfeiting either copy number or nonselective stability. We identified sites in the 2-microns plasmid that could be used for the insertion of genetic sequences without disrupting 2-microns coding elements and then assessed subsequent plasmid constructs for stability and copy number in vivo. We demonstrate the utility of a previously described 2-microns recombination chimera, pBH-2L, for the manipulation and transformation of 2-microns as a pure yeast plasmid vector. We show that the HpaI site near the STB element in the 2 microns plasmid can be utilized to clone yeast DNA of at least 3.9 kb with no loss of plasmid stability. Additionally, the copy number of these constructs is as high as levels reported for the endogenous 2-microns. PMID- 1857756 TI - The processing of inflected words. AB - Is an inflected word identified by first decomposing it into stem plus suffix or, instead, is it recognized as a whole? Several lexical decision experiments studied the recognition of inflected words in English (a language with few inflections) and Serbo-Croatian (a heavily inflected language). If recognition depended on decomposition, preceding the inflection with a brief exposure of the stem (less than 100 ms) should have primed the lexical entry for the stem and, therefore, facilitated recognition of the whole inflected word that followed. It did not. It was also found that the speed of recognizing an inflected word was more strongly associated with the frequency of the whole inflected form than with the frequency of its stem. The results suggested that in word recognition, lexical contact is first made with the whole word form. Nevertheless, morphological decomposition may still occur in subsequent processing. PMID- 1857757 TI - The contribution of morphology to word recognition. AB - Evidence of morphological processing was investigated in three word recognition tasks. In the first study, phonological ambiguity of the base morpheme in morphologically complex words of Serbo-Croatian was exploited in order to evaluate the claim that the base morpheme serves as the unit by which entries in the lexicon are accessed. An interaction of base morpheme ambiguity and affix characteristics was obtained and this outcome was interpreted as evidence that all morphological constituents of a word participate in lexical access. In the second study, facilitation due to morphological relatedness of prime and target was observed with Serbo-Croatian materials in the lexical decision and naming versions of the repetition priming task and results were interpreted as evidence of a morphological principle of organization among whole-word forms in the lexicon. In the third study, morphological affixes of both English and Serbo Croatian words were segmented from a source word and affixed to a target word more rapidly than phonemically matched controls. Results suggest that the morphological constituents of complex words are available in some word recognition tasks and that morphological knowledge is represented in the speaker's lexicon. PMID- 1857758 TI - Phonological deficits: beneath the surface of reading-acquisition problems. AB - In Experiment 1, the performance of young retarded readers on speech-segmentation tasks was compared with the performance of normal subjects matched for chronological age (CA) and with subjects matched for reading age (RA). Retarded readers were poorer than both control groups in consonant deletion, while there was no difference between the groups on a rhyme-judgement task and a syllabic vowel-reproduction task. In Experiment 2, another group of reading retarded children was compared with CA and RA controls on the classification of pseudo words, either by common phoneme or by overall phonetic similarity. The retarded readers made fewer classifications based on common phoneme than both control groups, while there was no difference between the groups in classifications based on overall phonetic similarity. In Experiment 3, adult developmental dyslexics were compared with normal adults in the tasks of Experiments 1 and 2. The dyslexics made fewer classifications based on a common phoneme than the normals, while no difference was found in classifications based on overall phonetic similarity. PMID- 1857759 TI - Hydrogen peroxide induced reproductive and interphase death in two strains of L5178Y murine lymphoma differing in radiation sensitivity. AB - L5178Y-R (LY-R) and L5178Y-S (LY-S) cells, differing in radiation sensitivity and susceptibility to the radiosensitizing effect of benzamide (Bz) were examined for susceptibility to hydrogen peroxide. Survival and chromatid aberration frequency indicated that LY-R cells were considerably more sensitive to H2O2 than LY-S cells. So, LY strains were found to be inversely cross-sensitive to X/gamma rays and H2O2. The relative resistance to H2O2 corresponded with the previously found twofold difference in catalase activity (Jaworska et al. 1987). At higher concentrations H2O2 treatment caused interphase death, that was delayed by benzamide (Bz, 2mM), an inhibitor of poly(ADP-ribosylation), to a lesser extent in the more resistant cell subline (LY-S). From the examination of the H2O2 induced increase in the free Ca2+ concentration (with or without 2 mM Bz treatment) with the use of Fura-2 it followed, that the cells responded to the oxidative stress by Ca2+ release. The Ca2+ concentration increase was neither directly related to the killing effect of H2O2 treatment, nor did it correspond with the twofold difference in catalase activity in LY strains. PMID- 1857760 TI - Direct evidence that radiation induced micronuclei of early embryos require a mitosis for expression. AB - The naturally synchronous development of early mouse embryos was exploited to address the question, whether micronuclei require a mitosis for expression or whether they can be expressed in the same cell cycle, in which exposure to X-rays or caffeine took place. Experiments with 2-cell and with 4-cell embryos showed that micronuclei are expressed only if a mitosis is completed. There was no indication, even after doses up to 20 Gy, that micronuclei can be expressed before the mitosis was reached, which followed exposure. Furthermore, no nuclear fragmentation pointing to apoptosis could be detected in the cycle, in which cells were exposed. The same results were obtained when caffeine (5 mM) was used as micronucleus inducing agent. PMID- 1857761 TI - Repair of damage caused by UV- and X-irradiation in the amoeboflagellate Naegleria gruberi. AB - Cysts of Naegleria gruberi have a normal UV- and an extremely high X-ray resistance compared to other protozoans. Caffeine and 3-aminobenzamide applied to excysting amoeba after irradiation in the encysted state (UV and X-rays) by feeding with drug-containing bacteria increased lethality, while fractionated irradiation (UV) and liquid-holding (UV and X-rays) increased survival. Illumination with visible light after UV-irradiation restored almost 100% viability. The results are discussed in regard to the activity of repair mechanisms. PMID- 1857762 TI - Photo-induced riboflavin binding to the tryptophan residues of bovine and human serum albumins. AB - The photobinding between riboflavin and the Trp residues from human and bovine serum albumins at two pH-dependent protein conformations was studied. At pH 7.0 both proteins showed photo-adduct formation with hyperbolic kinetics. In the bovine serum albumin this is attributed to the different locations of the two Trp residues. In the case of the human serum albumin, which has only one Trp residue, this behaviour may be related to different molecular conformations of the protein, as is also manifest in the iodide quenching experiments. At pH 3.5, the kinetics of the photo-adduct formation were found to be slower and showed a monophasic behaviour. These results are due to the conformational change of these proteins at acidic pH; the Trp residues of both proteins being now located in a more hydrophobic environment. When bovine serum albumin was anaerobically irradiated at pH 7.0 in the presence of 14C-riboflavin and then cleaved by CNBr, two peptides were obtained, containing the Trp-134 and Trp-212 residues, respectively. The incorporation of 14C-riboflavin in these samples was significantly higher at the level of the peptide containing the Trp-134 residue. Furthermore, it was demonstrated, that the energy transfer from enzymatically generated triplet acetone to riboflavin can also promote the binding of this vitamin to the Trp residues of human and bovine serum albumins. PMID- 1857763 TI - Cs-134/137 contamination and root uptake of different forest trees before and after the Chernobyl accident. AB - The Cs-134/137 activities were measured from different tree organs of spruce, larch and sycamore maple. Two locations in South Bavaria were monitored during a period of 2.5 years following the Chernobyl accident. Samples taken in 1985 allow to determine the Cs-137 contamination before the accident. Increasing Cs-137 activities from older to younger needle years of Picea abies caused by root uptake of the global weapons' fallout are due to the high phloem mobility of this element and the remaining of the needles at the tree for about 6-7 years. In contrast, the Cs-137 activity was much smaller in leaves of larch and sycamore maple. After the Chernobyl accident, the higher contamination of spruce greater than larch greater than sycamore maple is dependent on the roughness of bark, absolute bark surface and the existence of leaves during the deposition of Chernobyl-derived radioactivity. The Cs-134/137 activity (Bq/kg d.w.) was about 25-times higher in bark compared to wood of Picea abies and 1.5-4.7 times higher in directly contaminated twig-axes than in leaves. Till the end of the investigation the major contamination of the shoots was due to direct deposition of cesium on the trees. A maximum of 5-15% of the total activity of the directly contaminated branches of the plants was calculated to be part of root-uptake, depending on the amount of initial retention. 20% of the translocated cesium into new leaves of larch and about 50% into sycamore maple resulted from root-uptake 2.5 years after the accident. PMID- 1857764 TI - Psychiatric management of sleep disorders. AB - This chapter will focus on the office management of psychiatric patients with sleep disorders. Psychiatric aspects of insomnia, the parasomnias, circadian rhythm disorder and disorders of excessive sleepiness will be reviewed. The antidepressants, electroconvulsive therapy, amino acids and bright lights. PMID- 1857765 TI - The assessment and management of the suicidal patient. AB - This chapter will be oriented toward the problem faced by the clinician in attempting to prevent suicide in patients under treatment. It will focus on the clinician's difficult task of assessing suicide potential and initiating interventions to prevent suicide in patients at high risk. Specifically, the state of the art in identifying the suicidal patient will be reviewed, and various interventions available to the clinician will be discussed. PMID- 1857766 TI - Neuropsychiatric aspects of AIDS and psychopharmacologic management. AB - This article will review the current literature on the wide range of neuropsychiatric symptoms and syndromes seen in HIV illness. It will then describe the literature and the authors' experience in the use of psychotropic medications in this illness. PMID- 1857768 TI - Salaries and benefits. PMID- 1857767 TI - Investigational drugs and research. AB - This chapter will define investigational use for clinicians and outline FDA policies in this area in a simple and pragmatic way. Instances in which investigational use would require application to the FDA for an investigational New Drug Exemption (IND) and instances in which their use would require approval by an Institutional Review Board (IRB) will be described and examples given. PMID- 1857770 TI - It takes two. PMID- 1857769 TI - Case #1. Pyogenic granuloma. PMID- 1857772 TI - Dear RDH. PMID- 1857771 TI - Using effective aseptic procedures. PMID- 1857773 TI - Patient profile. PMID- 1857774 TI - Patient #1. PMID- 1857775 TI - Moms, kids and career. PMID- 1857776 TI - Sciences are basics for oral healthcare. PMID- 1857777 TI - Negative control by Sandostatin on pancreatic and duodenal growth: a possible implication of insulin-like growth factor I. AB - This study was undertaken to evaluate the effects of Sandostatin, a potent somatostatin analogue, on pancreatic and intestinal growth and plasma and pancreatic levels of insulin-like growth factor I, a known growth factor. Rats weighing 320-330 g, equipped with an intravenous cannula were infused with either bovine serum albumin or Sandostatin at a dose of 5 micrograms kg-1 h-1 for 7 days. Sandostatin caused significant reductions in pancreatic and intestinal weights accompanied by decreases in total DNA, RNA in both organs and total protein in the intestine while total pancreatic enzymes were increased. Plasma cholecystokinin and insulin-like growth factor I were reduced whereas total insulin-like growth factor I pancreatic content was increased. It is suggested that Sandostatin may reduce growth of these two organs by decreasing cholecystokinin and insulin-like growth factor release and their specific effects at the pancreatic and duodenal cellular level. PMID- 1857780 TI - [Luigi Oliva (1923-1991)]. PMID- 1857779 TI - Distribution and function of brain natriuretic peptide in the stomach and small intestine of the rat. AB - The distribution and function of brain natriuretic peptide (BNP) was studied in the rat stomach and jejunum. BNP-like immunoreactive nerves were found in the myenteric plexus, circular muscle, submucosa and in the crypt region of the jejunum. In the stomach, BNP-like immunoreactivity was found in the myenteric plexus, circular muscle, submucosa and at the base of the gastric glands. In the submucosa, BNP-like immunoreactivity was often associated with blood vessels. In segments of rat jejunum mounted in Ussing chambers, serosal exposure to rat BNP caused a concentration-dependent increase in short circuit current. A maximal effect of 18 +/- 4 microA/cm2 was observed with 1 microM BNP. The effect was quantitatively and qualitatively similar to that elicited by serosal exposure to equimolar atrial natriuretic peptide. The response to BNP was reduced by 88% in chloride free Kreb's buffer, by 83% in tissues pretreated with cinanserin, an antagonist of the 5-HT2 subtype of the 5-hydroxytryptamine receptor, and by 96% in tissues pretreated with tetrodotoxin, a blocker of axonal conduction. These results are consistent with a physiological role for BNP as a neuromodulator of gastrointestinal electrolyte transport. PMID- 1857778 TI - Effects of pancreastatin and chromogranin A on insulin release stimulated by various insulinotropic agents. AB - The effects of porcine pancreastatin on insulin release stimulated by insulinotropic agents, glucagon, cholecystokinin-octapeptide (CCK-8), gastric inhibitory polypeptide (GIP) and L-arginine, were compared to those of bovine chromogranin A (CGA) using the isolated perfused rat pancreas. Pancreastatin significantly potentiated glucagon-stimulated insulin release (first phase: 12.5 +/- 0.9 ng/8 min; second phase: 34.5 +/- 1.6 ng/25 min in controls; 16.5 +/- 1.1 ng/8 min and 44.0 +/- 2.2 ng/25 min in pancreastatin group), whereas CGA was ineffective. The first phase of L-arginine-stimulated insulin release was also potentiated by pancreastatin (6.9 +/- 0.5 ng/5 min in controls, 8.4 +/- 0.6 ng/5 min in pancreastatin group), but not by CGA. Pancreastatin did not affect CCK-8 or GIP-stimulated insulin release. Similarly, CGA did not affect insulin release stimulated by CCK-8 or GIP. These findings suggest that pancreastatin stimulates insulin release in the presence of glucagon. Because pancreastatin can have multiple effects on insulin release, which are dependent upon the local concentration of insulin effectors, pancreastatin may participate in the fine tuning of insulin release from B cells. PMID- 1857781 TI - [High resolution tridimensional study of the blood vessels of the neck and the intracranial circulation with magnetic resonance angiography]. AB - Magnetic Resonance Angiography (MRA) is a modern vascular imaging technique which allows the noninvasive and direct imaging of vessels. The authors aimed at evaluating the diagnostic accuracy of MRA in the study of pathologic conditions in the neck and intracranial vessels; spatial resolution of the technique was also investigated. Twenty-four healthy volunteers and 82 patients suffering from various diseases of the head and neck vessels were included in the study. First of all, MRA capabilities were investigated in visualizing normal vessels of both neck and intracranial circle. The diagnostic accuracy of the method was then evaluated in the study of vascular diseases, and the results compared with conventional/digital angiographic findings. The comparison demonstrated how stenoses and atherosclerotic plaques tend to be overestimated by MRA because of technical artifacts inherent to the technique itself, whereas vascular ulcerations and aneurysms are frequently underestimated. However, this data was steady and therefore evaluable--the exact knowledge of the artifacts making diagnosis reliable. The diagnostic and technical problems relative to the various vascular diseases are discussed. Finally, several hypotheses of diagnostic iter are suggested. PMID- 1857782 TI - [Comparison of magnetic resonance angiography and digital angiography of the epiaortic vessels]. AB - Atheromasic lesions and other pathologic conditions of the arterial vessels of the neck are the most frequent causes of cerebrovascular disease. Diagnostic imaging currently employs digital subtraction angiography (DSA), Doppler, and color-Doppler US to study these conditions. Digital subtraction intraarterial angiography (DSAA) can provide both an early diagnosis and an accurate preoperative depiction of neck vessels; however, in spite of its effective value, it still remains an invasive technique. Magnetic Resonance angiography (angio-MR) is the latest technique allowing the depiction of neck vessels morphology. It shares with digital angiography the capability of supplying spatial depiction of all the examined vascular structures, and with US its noninvasiveness. The authors investigated angio-MR capabilities in providing accurate and detailed images of neck arteries; the images were then compared with DSA ones. Thirty patients with cerebrovascular diseases were studied. MR imaging was performed with a 1.5 T unit with a dedicated coil, and gradient-echo sequences were employed. Refocused sequences for flow were acquired on both the coronal and the sagittal planes, with the following parameters: TR 40, TE 10, flip angle 25 degrees, acquisition volumes 80-35 mm, 64-15 frames. Digital angiography demonstrated 101 vascular lesions: 27 slight stenoses (less than 30%), 19 mild stenoses (31-70%), 12 severe stenoses (71-99%), 7 occlusions, 14 coilings, 7 kinkings, and 15 hypoplasias of vertebral artery. In slight stenoses, angio-MR underestimated the condition in 11/27 patients. In mild and severe stenoses, as well as in occlusive diseases, angio-MR tended to overestimate the condition. In coiling, kinking, and hypoplasia, angio-MR yielded the same results as DSA. PMID- 1857783 TI - [Magnetic resonance in the study of the temporo-mandibular joint. I. Anatomo functional findings]. AB - Thirty-four temporomandibular joints (TMJ) were examined in 17 normal subjects with two superconductive MR units at 1T and 1.5T. TMJ evaluation was performed with both SE sequences in occlusal position and with "fast" sequences (flash) during the gradual opening of the mouth. Therefore, both the anatomic features of the TMJs and their dynamic behavior during mouth opening were analyzed. The information acquired allowed the complete and non-invasive evaluation of TMJ function. The knowledge of the normal anatomic and functional patterns is of paramount importance for the diagnostic approach to TMJ pathologic conditions. PMID- 1857784 TI - [Magnetic resonance imaging in study of the temporo-mandibular joint. II. Pathologic findings]. AB - A total of 107 temporomandibular joints (TMJ) were examined with two superconductive MR units at 1T and 1.5T. In 73 TMJs, MR revealed 55 disk displacements, 7 disk perforations, 10 joint space adhesions, 33 osteoarthrities, 3 avascular necroses of the mandibular condyle, and 25 joint effusions. These abnormalities are described and discussed. In spite of some limitations--e.g., motion artifacts and patients' claustrophobia--MR imaging is the procedure of choice in abnormal TMJs, because it yields useful information as to therapeutic choice (conservative versus surgical). Arthrography can be used as a complementary study technique in the patients with marked disagreement between clinical and MR findings. Arthroscopy should be used as a surgical procedure in abnormal TMJs selected by previous MR studies. PMID- 1857785 TI - [Primary empty sella. Incidence in 500 asymptomatic subjects examined with magnetic resonance]. AB - In 500 consecutive patients, aged 11-82 years, who underwent MR imaging of the brain for a variety of conditions not related to pathologic processes of the sellar or juxtasellar regions, the authors detected primary totally empty sella in 28/248 males (11.3%) and in 34/252 females (13.5%). Primary partially empty sella was found in 40/248 males (16.1%) and in 38/252 females (15.1%). A progressive increase in the incidence of the signs of primary empty sella was observed with aging, the increase being more conspicuous in the 5th decade of life in females (37.5%) and in the 6th decade in males (40%). On the whole, signs of primary empty sella were detected in 140/500 cases (38%)--namely, in 9.6% of the subjects under 40 and in 39.9% of those above 40. The incidence of primary empty sella, unrelated to any other clinical condition, seems to support its inclusion into paraphysiologic variants. On the basis of the data reported in literature, the authors consider the factors possibly playing a role in this condition. They seem to be: insufficiency or absence of diaphragma sellae, CSF pressure, and pituitary involution related to aging. PMID- 1857786 TI - [Feasibility of magnetic resonance-guided fine-needle percutaneous biopsy]. AB - Fluoroscopic, US, and CT guidance to aspiration cytology are valuable tools for oncologic diagnosis. MR imaging is now replacing CT as the imaging method of choice to guide biopsy mainly in the abdomen and pelvis. The standard needles used for CT-guided biopsy are unsuitable for MR guidance because ferromagnetic artifacts shade the underlying anatomy. A new needle specifically designed for MR guidance allowed MR-guided aspiration biopsies to be carried out in a group of 17 patients with different neoplastic diseases. To locate the lesion and to assess its depth, a glass pipette containing a diluted solution of paramagnetic contrast medium (Gd-DTPA) was placed on the skin surface. In 13/17 patients (76.5%), biopsy was successful and histology and/or cytology allowed a diagnosis to be made. In spite of their longer measurement times, T1-weighted SE images clearly demonstrated both needle and lesion. On the contrary, fast images (FLASH, 15 degrees-90 degrees), with/without breath holding, although much shorter (7 s), were often useless, due to artifacts, mainly in small lesions. PMID- 1857787 TI - [Painful gleno-humeral joint instability in athletes. Radiographic findings]. AB - Instability of the glenohumeral joint is a common cause of chronic shoulder pain and disability in athletes using repetitive arm movements in elevation and external rotation. A series of 29 athletes with persistent shoulder discomfort for transient subluxation was evaluated with plain radiography and tomography in right axillary projection. The purpose was to detect abnormalities in the osseous glenoid rim. Twenty-six patients (89.6% of all cases studied) had various degrees of skeletal damage, including 18 fractures (69.2%) of the anterior rim, 2 (7.6%) of the posterior rim, and 6 cases (23.07%) of local degenerative changes; 3 cases were negative for skeletal damages. The result of this study demonstrate conventional radiography to be useful in the diagnostic assessment of shoulder pain in athletes, where similar problems must be promptly detected and not ignored. PMID- 1857788 TI - [Radiologic and clinical aspects of osteoarticular amyloidosis caused by dialysis]. AB - Many long-term (greater than 60 months) hemodialysis patients develop a severe osteoarticular disease, called "dialysis arthropathy", which is characterized by the deposition in bone and synovia of a new type of amyloid made mainly of beta 2 microglobulin. In the present study, 31 patients (17 males, 14 females; age 54.1 +/- 13 years), undergoing chronic hemodialysis for 60-125 months, were examined for dialysis arthropathy by means of clinics and of radiological investigations (conventional radiography and computed tomography). Sixteen patients (51.6%) had radiographic evidence of dialysis arthropathy: geodes (shoulders, 12 cases; wrists, 11; hips, 2; knees, 2) and/or destructive arthropathies (cervical spine, 13 cases, dorsolumbar spine, 2; hands, 2; hips, 1). Within 24 months, these lesions were found to progress slowly in the majority of cases. In the diagnostic process, CT should be employed in the study of spine, shoulders and hips when the lesions have not been sufficiently demonstrated by conventional radiography in the presence of evident clinical signs. Patients with dialysis arthropathy had undergone dialysis for longer periods than those without it (p less than 0.005) and showed a significantly higher incidence of both carpal tunnel syndrome (p less than 0.0005) and shoulder pain (p less than 0.005). Our findings confirm the high incidence and clinical importance of dialysis arthropathy in long-term hemodialysis patients and the value of diagnostic imaging in screening such patients for those lesions. PMID- 1857789 TI - [Ultrasonography in the study of lesions of the menisci and the collateral ligaments of the knee. Findings in 48 surgically treated patients]. AB - The authors report the results of the study of 48/112 patients who underwent US examination of the knee for gonalgia. Meniscopathy or capsular-ligamentous lesions were clinically suspected. US results were compared with arthroscopic or athrotomic findings; the latter two methods were considered as the reference gold standard. US exhibited 81.2% overall diagnostic accuracy, thus confirming its limitations, more evident than those of arthroscopy and arthrography, CT and MR imaging. Major limitations of US were its failed recognition of meniscal tears smaller than 5-6 mm, and its failed distinction of degenerative meniscopathies from common meniscal fractures (with the exception of 2 cases). Moreover, US did not allow cruciate ligament lesions to be demonstrated; however, in all these cases, US did demonstrate increased capsular thickness (greater than 3 mm at the lower margin of femoral condyle). This indirect sign, together with roudness of parameniscus and capsular-ligamentous limitans (at the hemirhyme), and the direct sign of inhomogeneous hyperechogenicity of the meniscal triangle (normally hypoechoic) contributed to raising overall diagnostic accuracy of US to 89.9%. In the 5 patients with a suspected lesion of the medial collateral ligament examined within 48 hours from trauma, US gave 2 false-positive results in 2 cases where forced abduction test was also positive. Massive edema and swelling of adjacent structures prevented the correct evaluation of ligament limitans. In these 2 cases, a lesion in the anterior cruciate ligament was found at surgery; one of them was associated with a meniscal lesion already diagnosed at US. Both parameniscal and popliteal cysts were correctly diagnosed with US. Due to the well-known limitations of clinics in the diagnosis of knee pain, US could be suggested as the examination of choice to evaluate suspected meniscopathy or ligamentous lesions, thanks to its low cost and short execution time. The use of US could also spare the patients more invasive examinations--e.g., arthroscopy and arthrography--and more expensive ones--e.g., CT and MR imaging. PMID- 1857790 TI - [Ultrasonography of the borderline between normal and pathological state of the hip in newborn infants (borderline hip)]. AB - Infant hips are classified, according to Graf, in 4 US types on the basis of the morphologic changes in both the cartilaginous and the bony roofs (type I, II, III, IV). Out of 6,000 examined hips, 170 (2.8%) were considered, which could be classified neither as type I (mature) nor as type II (delayed/immature ossification). These hips were called borderline hips. They exhibited some characteristic US features: good bone modeling, rounded cotyle, and alpha angle 60 degrees +/- 2. They were always observed during the first month of the patients' life. Anamnestic data were not specific (27.5% breech delivery, and 13% oligohydramnios); clinics sometimes overestimated the actual anatomic development (64/170 cases with positivity of Ortolani's sign and/or restricted abduction; 25% of patients presented with no suspicious signs). Dynamic hip examination showed only physiological cranial deflection of the cartilaginous roof. Finally, borderline hips developed into type I hips in 99% of cases, within the third month of the patients' life. PMID- 1857791 TI - [Role of color coded duplex sonography in the study of thyroid pathology. Personal experience]. AB - The authors examined 110 patients with suspected pathologic conditions of the thyroid by means of color-coded duplex US. In addition to the information yielded by conventional US, this technique allows organ vascularization to be demonstrated. Five normal patients were considered as a control group: no tissue vascularization was demonstrated in these cases. In 8 patients presenting with carcinoma or recurrences, vascularization was markedly increased both peripheral and central to the nodule. A few doubts are still to be solved as to the diagnostic value of color-coded duplex US in the evaluation of non-carcinomatous nodular pathologic conditions. As a matter of fact, non-functioning avascular adenomas can be demonstrated only in a very low percentage of cases (66%). Color coded duplex US proved extremely sensitive and specific in depicting malignant neoplasms. Moreover, the use of fine-needle biopsy could be optimized and subsequently reduced. Color-coded duplex US proved to be markedly superior to other methods and techniques in the study of thyroid diseases, especially thyroiditis and multiple pathologic conditions. The simultaneous presence of hypocapture at scintigraphy and peripheral and central vascularization in a single nodule or within multinodular struma at color-Doppler was highly suggestive of malignant thyroid neoplasm. Color-coded duplex US is a low-cost technique, which can be performed on an outpatient basis. Moreover, it is not invasive, nor does it damage the thyroid. That is why its use is almost mandatory in the study of pathologic conditions of the thyroid. PMID- 1857792 TI - [Diagnostic reliability of ultrasonography in the preoperative staging of the N parameter in head and neck neoplasms]. AB - The demonstration of metastatic involvement of neck nodes is a crucial step in the staging of patients with head and neck tumors. Diagnostic accuracy, sensitivity, and specificity of US in the detection of lymph node metastases were evaluated in 48 patients with this type of malignancy. The patients subsequently underwent surgical node dissection. Comparison of US, clinical and histological data demonstrated US to have 93.7% diagnostic accuracy, 100% sensitivity, and 84% specificity--the corresponding clinical values being 81%, 79%, and 84%, respectively. Among several US parameters, a substantial role in differentiating metastatic from tumor-free lymph nodes was played by the evaluation of roundness index (RI), and by the demonstration of an intranodal hyperechoic stria: RI value was always higher than 2 in tumor-free nodes and the hyperechoic stria was always absent in metastatic nodes. US approach never failed to demonstrate metastatic nodes while clinics missed them in 6 patients. Thus, US appears the most valuable diagnostic tool for staging head and neck tumors; its diagnostic accuracy can be increased by the combination with US-guided aspiration biopsy. PMID- 1857793 TI - [Double-contrast enema. Study of the mucosal pattern and the organ profile with conventional and digital methods]. AB - A solid state digital system (FCR 101) was employed in our comparative evaluation of the image quality of conventional versus digital techniques in the study of colon by means of double-contrast enema. Sixty patients were examined with a single AP view, using digital radiography with 100% radiation dose and progressive 50% and 75% reductions; the radiographs thus obtained were then compared with the corresponding conventional ones. The examined parameters were organ profile and mucosal pattern. Each digital and conventional radiograph was evaluated by 2 independent radiologists and a value was given to each parameter i.e., 1 = good, 2 = sufficient, 3 = insufficient. Upon comparison of the average values obtained for digital and conventional radiographs in optimal conditions and with a dose reduced by 50%, the digital technique was seen to give a more detailed and accurate representation of both low-contrast mucosal pattern and of organ profile. With the dose reduced by 75%, a slight increase was observed in background noise which caused a slight loss in image definition, but this did not reduce image readability with respect to conventional radiographs. To conclude, the digital method with a 50% exposure reduction is to be preferred in the examination of the colon, especially in pediatric radiology; furthermore, since this technique allows better detailing at lower contrast, it is to be preferred in the study of the pathologic conditions affecting mainly/only the mucosal pattern--e.g., cancer, ulcerative colitis, Crohn's disease, and so on. An exposure dose reduced by 75% may be used for following lesions previously diagnosed and when a less detailed depiction of the mucosal pattern is enough. PMID- 1857795 TI - [Radiology of craniofacial trauma]. PMID- 1857794 TI - [Diagnostic role of echography in acute appendicitis in children]. AB - Eighty-seven pediatric patients with suspected acute appendicitis underwent high resolution US with graded abdominal compression. The study was limited to the patients with a questionable clinical diagnosis, accounting for about 40% of the patients examined for acute appendicitis in our Institution. US had 87.3% accuracy, 81.5% sensitivity, and 90% specificity. The main US findings in the positive cases were: visualization of the appendix as a tubular non-compressible structure, with a diameter of 5 mm or more, symmetric/asymmetric wall thickening, possible presence of appendicoliths and variable appearance of the central echogenic layer (preserved, doubled for lumen dilatation, partially/totally lost). The above US findings were grouped in 3 basic patterns: type I (thickened appendix with no structural abnormalities) appeared to be related to non suppurative and phlegmonous acute appendicitis; type II (detectable appendiceal abnormalities) was observed both in phlegmonous and in suppurative acute appendicitis; type III (pericecal complex mass, frequently with appendicoliths) was found in all cases of periappendiceal abscess. In our experience, the use of US in the diagnosis of acute appendicitis in children allowed a reduction by about 2/3 in the rate of unnecessary laparotomies. Such a finding emerges from the comparison with the results obtained in the 2 years prior to the use of US. The technique also allowed an unquestionable diagnosis of acute appendicitis or periappendiceal abscess to be made in a number of clinically equivocal cases, thus avoiding potentially harmful delays in diagnosis. On the other hand, the incidence of false-negatives on US is not negligible, which calls for a cautious clinical and US evaluation of all equivocal cases following no typical US pattern. PMID- 1857796 TI - [Ultrasonography in medical nephropathies]. PMID- 1857797 TI - [Development of a pendular irradiation technique, using a moving bar, for the treatment of head and neck tumors]. PMID- 1857798 TI - [Role of postoperative adjuvant radiotherapy in the treatment of class T2-3 NO MO adenocarcinoma of the kidney]. AB - From 1968 to 1983, in the Department of Urology and in the Institute of Radiotherapy of the University of Brescia, the role of postoperative radiotherapy (PORT) in 95 patients with renal adenocarcinoma (T2-3 N0 M0) was investigated. From 1968 to 1978, 46 patients underwent radical nephrectomy and PORT; from 1978 to 1983, 49 patients were submitted to radical nephrectomy with regional lymphadenectomy (CH). Overall survival (PCS) at 5 years is 63% (PORT) vs 57% (CH) (p greater than 0.05). The probability of survival is better for left-sided neoplasms than for right-sided ones. In the CH group, the 5-year PCS is 40% vs 70%, respectively, for right vs left neoplasms (p less than 0.05); in the PORT group, PCS is 59% (right) vs 70% (left). For right-sided cancers, 5-year PCS is higher for PORT (59%) than for CH (40%) patients (p less than 0.05). In the PORT group acute bowel toxicity was 24% (grade 2, WHO). In 2 patients only (4.3%) PORT was stopped because of toxicity. PORT sequelae were investigated in: spinal cord, contralateral kidney, liver and bowel. Bowel sequelae (grade 2, Dische) were observed in 3 patients only (6.5%). In the T2-3 N0 M0 classes, radical nephrectomy with PORT may give the same results as aggressive surgery, with a low biological cost. Prognostic data might mean a different and more favorable loco regional evolution for left-sided renal cancers. PMID- 1857799 TI - [Mammographic control after quadrantectomy and radiation therapy]. AB - The efficacy of combined surgery and radiation therapy in the treatment of breast cancer has increased the use of mammography in the follow-up to detect early recurrences. The authors report their experience in the follow-up of 43 breast cancers after treatment with local excision, axillary dissection, and irradiation. Mammography was performed at 6.12, and 24 months. The radiological findings were: 38/43 (88.3%) breasts with abnormal mammographic patterns, skin thickening in 36/43 (83.7%) cases, breast retraction in 16/43 (37.2%), architectural distortion in 17/43 (39.5%), increased parenchymal density in 33/43 (76.7%), calcifications in 6/43 (13.9%), and a mass in 10/43 (23.2%) cases. The authors describe histologic changes, corresponding to mammographic findings, and evolution of the treated breasts. Suspicious findings were microcalcifications in one case and a mass in 6 cases (4 of them at 6 months and 2 at 12). Excisional biopsy, performed in the above 7 patients, confirmed recurrence in 4 cases. In 3 cases with negative pathology, where the malignant nature of the lesion could not be demonstrated, we observed: a cluster of microcalcifications undistinguishable from neoplasm in 1 case and spiculated nodules with architectural distortion in the extant 2 cases. Further limitations of mammography were due to radiological density of the breast in one case, and to its minimal size in another--these elements delayed both correct interpretation of mammographic findings and final diagnosis. The low agreement between mammography and histology proved the difficulty of both analysis and evaluation of abnormal post-irradiation breast tissue. The authors, in agreement with literature reports, suggest the schedule for clinical and mammographic follow-up. PMID- 1857800 TI - [Progressive multiple sclerosis. Evaluation of the effectiveness of total lymph node irradiation]. AB - A long-lasting immunological suppression action seems to be produced by total lymphoid irradiation; some authors emphasize the favorable effect of this treatment on chronic progressive multiple sclerosis. In order to evaluate the actual role of TLI, 6 patients affected with chronic progressive multiple sclerosis were submitted to TLI with shaped and personalized fields at the Instituto del Radio, University of Brescia, Italy. The total dose delivered was 19.8 Gy in 4 weeks, 1.8 Gy/day, 5d/w; a week elapsed between the first and the second irradiation course. Disability according to Kurtzke scale was evaluated, together with blood lymphocyte count and irradiation side-effects, over a mean follow-up period of 20.8 months (range: 13-24). Our findings indicate that: a) disease progression was not markedly reduced by TLI; b) steroid hormones responsivity was restored after irradiation, and c) side-effects were mild and tolerable. PMID- 1857801 TI - [Role of CT in radiotherapy radiation planning for tumors of the rhinopharynx]. AB - The authors compare the results obtained by CT with clinics and conventional radiography in the staging of nasopharyngeal tumors. The accurate evaluation of tumor size, localization, and spread, helps optimize treatment planning and fit radiation boosts on small fields. Twenty-six patients underwent clinical examination, radiography of the skull and neck, lateral stratigraphy of epipharynx, and CT of head and neck. We compared the results obtained in the study of: nasopharyngeal walls, parapharyngeal space, paranasal sinuses, nasal cavity, bone erosion of the base of skull, and continuous invasion without bone erosions. Our results point to conventional radiology as the examination of choice for the study of upper nasopharyngeal wall, while CT allows a better evaluation of the lateral wall, and is clearly superior in demonstrating parapharyngeal space, contiguous intracranial invasion, and neck nodes involvement. PMID- 1857802 TI - [Patient exposure during radiodiagnosis. The Nationwide Evaluation of X-ray Trends (NEXT) program in Italy]. AB - The aim of this paper is the critical analysis of the results obtained with the quality control program in X-ray diagnosis called NEXT (Nationwide Evaluation of X-ray Trends). It is also aimed at comparing the above results with guidelines and trends of international radiology, for both technical features and patient protection from radiations. The main purpose of patient protection is the reduction of unnecessary exposure through the optimization of radiodiagnostic procedures. In order to identify the fields requiring the application of specific quality control programs, the Istituto Superiore di Sanita, together with ENEA/DISP have been running the NEXT program in Italy since 1977. The program, through data collection and measurements in more than 2,500 radiologic units, allowed both state of the art and progress in radiodiagnostic practice to be studied over a long period of time. Data computation provides, for a standard patient, the skin entrance exposure and the main organ doses for the examinations which are most frequently performed. In this paper, the fundamentals of the NEXT program are reported and the most significant results are discussed, and compared, when possible, with the values recommended by international scientific organizations. The analysis of the results demonstrates a decreasing trend in patient exposure over the last years. PMID- 1857803 TI - [A case of primary non-Hodgkin's lymphoma of the breast. Mammographic and sonographic analysis]. PMID- 1857804 TI - [Patterns of transition between lymphangioma and intestinal lymphangiectasia. RAdiologic and histologic aspects of 2 cases with predominant involvement of the colon]. PMID- 1857805 TI - [Value of magnetic resonance in the diagnosis of spinal cord compression caused by vertebral hemangioma. Description of a case]. PMID- 1857806 TI - [A rare complication of Crohn's disease. Description of a case]. PMID- 1857807 TI - [Shooting in macro-stereo]. PMID- 1857808 TI - [Influence of firing parameters on the optical properties of dental porcelains]. PMID- 1857809 TI - [Impression tray technique in photopolymerizing resin]. PMID- 1857810 TI - [Bronchiolitis obliterans organizing pneumonia (BOOP). Characteristics and boundaries of an anatomo-clinical entity]. AB - Bronchiolitis obliterans organizing pneumonia (BOOP) is defined by endoluminal obstruction of distal airspaces by a fibrous granulation tissue consisting of inflammatory cells, fibroblasts, and connective tissue. The morphogenesis of the process is the following: diffuse alveolar injury leading to basement membrane denudation and intra-alveolar exudate of fibrinogen, immunoglobulins, coagulation factors, fibronectin; intra-alveolar migration of interstitial fibroblasts through gaps of the epithelial basement membrane; intra-alveolar secretion of loose connective tissue (codistribution of collagens I, III, V, and fibronectin) by the fibroblasts-myofibroblasts. The main characteristic of this peculiar fibrosis is its possible reversibility. BOOP is not specific for any aetiology, and it is found in various conditions as infectious diseases, drug induced pulmonary diseases, connective tissue diseases. It is also present in other conditions where it is not the most contributive information to diagnosis (hypersensitivity pneumonitis, chronic eosinophilic pneumonia). But in some cases BOOP remains idiopathic and has to be individualized. Three clinical and imaging profiles are distinguished: the most characteristic consists of an inflammatory context with imaging patchy alveolar opacities, migrating and relapsing, and most steroid sensitive; the other two presentations are less remarkable: pseudo neoplastic localized chronic pneumonia, and diffuse infiltrative lung disease. BOOP is a clinico-pathologic entity that the clinician must know because of the efficacy of corticosteroid treatment in most cases, and it further represents an unique model to understand the pathogenesis of fibrosing pulmonary diseases. PMID- 1857811 TI - [Pleuro-pulmonary manifestations of rheumatoid polyarthritis]. AB - Sensitive investigations such as pulmonary function tests, broncho-alveolar lavage or computered tomography at high resolution enable pleuro-pulmonary disease to be detected in nearly 50% of those patients studied who had rheumatoid arthritis (PR). The prevalence of these manifestations is most usually elevated in male PR sufferers, those who are sero-positive or have associated extra articular signs such as sub cutaneous nodules. More recently there has been evidence of genetic risk factors linked to HLA grouping or Pi phenotype. Amongst the usual manifestations, the pleurisies and above all necrobiotic nodules, which are most often asymptomatic, sometimes pose difficult problems in differential diagnosis, particularly when they precede the articular disease. The diffuse interstitial fibrosis remains the most worrying specific complication due to the fact of its potential seriousness. The pathophysiology of this form of fibrosis is better understood since the introduction of LBA. In the absence of any specific controlled studies its treatment remains impirical and is similar to that given for diffuse or idiopathic interstitial fibrosis. Pulmonary vascularity, the bronchiolitis obliterans with organising pneumonia and apical fibrosis, very similar to Hamilton's syndrome, are much rarer manifestations. On the other hand non specific respiratory infections are the cause of death in 10 20% of cases. Bronchiolitis obliterans induced by D Penicillamine is the most severe iatrogenic manifestation, since corticosteroid therapy associated with immunosuppressive drugs enables at best a stabilisation of the alveo bronchiolar lesions. More recently there have been twenty observations of hypersensitivity pneumonia to low dose methotrexate. The prevalence of these pulmonary disorders during the treatment of PR is around 5%. However the respiratory contraindications of these drugs which are being used more and more and the methods of pulmonary surveillance under treatment are not yet defined. PMID- 1857812 TI - [Pulmonary dendritic cells]. AB - The dendritic cells were initially described in lymphoid organs and have been recently shown in the normal human lung at the level of the bronchioles, preferentially in the peribronchiolar connective tissue and in the alveolar parenchyma. Langerhans cells, which constitute a sub-population amongst the dendritic cells are equally present, but virtually exclusively limited to the bronchiolar epithelium. The pulmonary Langerhans cells probably derive from dendritic cells as in the skin. The number and state of differentiation of pulmonary dendritic cells vary as a function of the epithelial microenvironment which seems necessary in the differentiation of dendritic cells into Langerhans cells. Langerhans cells are frequently seen in zones of alveolar hyperplasia and/or alveolar metaplasia induced by tobacco or by inflammatory lesions. Dendritic cells and Langerhans cells have a potent capacity for presenting an antigen to lymphocytes. Their presence in the normal lung and their differentiation in the course of certain pathological pulmonary processes strongly suggest that they have a significant role in the pulmonary immune response as well as in the pathogenesis of certain diseases. PMID- 1857813 TI - [Mediastinal lymphatic staging of bronchial cancer. Respective value of x-ray computed tomography and magnetic resonance imaging. Radio-surgical comparison]. AB - Fifty patients with bronchogenic carcinoma were prospectively studied by both CT and MR during 10 days preceding thoracotomy. Results of CT and MR were compared with the surgical and pathology findings. No statistically significant difference was found between the two imaging methods for the evaluation of node involvement (N2). MR appear to be superior to CT in the aortopulmonary and subcarinal areas. PMID- 1857814 TI - [Postoperative pain after thoracotomy. A study of 116 patients]. AB - We have studied post-operative pain in 116 patients who underwent a thoracotomy. The pains were assessed using a visual analogue scale and were significant and identical whatever type of operation was used and irrespective of sex or diagnostic disease category. On the operative day only the surgeon seemed to have any influence. On the first post-operative day the pain was influenced by age and on the eighth day by socio-professional category. The insertion of drains had no influence on the pain. Massage and physiotherapy decreased the pain in a significant fashion. The importance of taking account of post-operative pain is underlined. PMID- 1857815 TI - [The effect of continuous peri-thoracic negative pressure on nocturnal desaturation of chronic obstructive bronchopneumopathies]. AB - The fall of functional residual capacity (FRC) in the genesis of nocturnal desaturation in chronic airflow obstruction (COPD) continues to be discussed. This hypothesis is being tested by applying a negative continuous thoracic pressure using a cuirass/poncho attached to a pump for one night (night II) after a control night with a cuirass/poncho at atmospheric pressure (night 1). Seven subjects with a mean age of 61 +/- 9, with a mean weight of 108 +/- 21% of their ideal weight, who were suffering from severe airflow obstruction with a mean forced expired volume (FEV1: 39 +/- 20% th., FEV1/FVC: 35 +/- 9%, PaO2: 60 +/- 3 mmHg, PaCO2: 42 +/- 4 mmHg). These seven subjects had two polysomnographies on the two successive nights. During night II, the FRC was increased by 0.33 +/- 0.6 L by applying a continuous negative thoracic pressure of 10 +/- 1 cm of water. A significant decrease in the sleep time was noted (248 +/- 86 min vs 316 +/- 74 min, p less than 0.02) also the efficacy of sleep (54 +/- 9% vs 71 +/- 15% vm p less than 0.02). There was no difference between the two nights as regards the distribution of the sleep stages. In 2 subjects, the hypopnoea-apnoea index passed from 0 to 11 and from 4 to 22 respectively. The principal result was the absence of any significant difference in mean nocturnal oxygen saturation between the two nights.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1857816 TI - [Interpretation of the values of urinary cotinine in smokers and non-smokers]. AB - The values of urinary cotinine measured using high performance liquid chromatography in 125 adults (44 men and 81 women) were compared with the degree of intoxication and/or exposure to tobacco experienced over six consecutive days by auto-questionnaire. The subjects were classified in 6 groups: non exposed non smokers and non smokers exposed for less than one hour (1, n = 16); non smokers exposed for between 1 and 10 hours (2, n = 26); non smokers exposed for more than 10 hours and less than 30 hours (3, n = 33); non smokers exposed for more than 30 hours (4, n = 13); smokers smoking less than 20 cigarettes per day (5, n = 16); smokers smoking 20 cigarettes or more per day (6, n = 21). The measurements were made on urine specimens from the first morning (fraction F1), from the day and night (F2) and those of the second morning (F3). The results were expressed in micrograms/fraction and were as follows: Group 1: 37.3 (F1); 149.5 (F2); 26.8 (F3)--Group 2: 81.2; 234.1; 75.4--Group 3: 121.1; 383.1; 80.7--Group 4: 98.8; 253.7; 117.2--Group 5: 206.9; 773.8; 188--Group 6: 483.1; 1908.2; 431.3. Cotinine was found in all individuals whether they declared that they were exposed or non exposed (with the exception of a single person amongs the latter). In spite of a certain amount of overlapping between the results of the individuals in groups 4 and 5, the values obtained enabled a differentiation between the degrees of tobacco absorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1857817 TI - [Disseminated toxoplasmosis in a patient with HIV infection]. AB - The authors describe a case of toxoplasmosis occurring in a subject who is HIV positive who presented with a cough and an infectious syndrome. Toxoplasma gondii was identified in the broncho-alveolar lavage even though the X-ray, the fibroscopy, blood gases and the broncho-alveolar lavage were normal. The frequency of pulmonary disease in the course of a toxoplasma infection in HIV subjects was underlined. Amongst the non invasive diagnostic methods the authors stress the value of broncho-alveolar lavage with a close search for toxoplasma even in the absence of any suggestive paraclinical anomalies. PMID- 1857818 TI - [Intralobar pulmonary sequestration manifested by neonatal cardiac insufficiency]. AB - The authors report the case of an intralobar pulmonary sequestration in a newborn presenting congestive heart failure. The clinical symptoms mimicked a persistent ductus arteriosus. Clinical, radiographic and echographic data suggested the diagnosis which was confirmed by the angiography. A surgical treatment was realised at seven weeks consisting in the ligation of the abnormal artery and a right lower lobectomy. This is the 9th case found in the literature. A congestive heart failure in a neonate with normal intracardiac anatomy may suggest a pulmonary sequestration. PMID- 1857819 TI - [Broncholithiasis of the upper right lobe]. AB - A case of right upper lobe broncholithiasis is reported in a 50 years old smoker man. The first diagnosis was bronchial carcinoma but the diagnosis was made finally by fiberoptic bronchoscopy and scannography. The outcome remains favourable without treatment. The value of scannography for diagnosis and follow up is underlined. PMID- 1857820 TI - [Hemoptysis disclosing a plasma cell granuloma with intra-bronchial involvement]. AB - The authors report a case of a plasma cell granuloma in a young woman of 19 with a past history of congenital rubella, presenting with repeated small haemoptyses related to a pedunculated endo-bronchial tumour. The diagnosis was only made per operatively, permitting an effective excision. PMID- 1857821 TI - [Icterohemorrhagic leptospirosis with acute respiratory distress syndrome and pulmonary hemorrhage]. AB - We report a case of the respiratory distress syndrome occurring in a patient with leptospirosis ictero-haemorrhagica (LIH). The respiratory failure was associated with pulmonary haemorrhage. There was a rapid favourable outcome after treatment with antibiotics and artificial ventilation. The diagnosis of LIH has been confirmed by serological examination. The mechanisms of the pulmonary disorder during the course of LIH were discussed. PMID- 1857822 TI - [Fever and the water-air level]. PMID- 1857823 TI - [Trans-thoracic cytologic puncture using fine needle aspiration]. PMID- 1857824 TI - [Asthma and infection: interrelations]. AB - The frequent interaction of infection in asthma is a result of a complex interrelationship. Infectious agents are capable both of inducing asthmatic crises and, at least for viruses, of initiating the asthmatic process. They also favour a specific IgE response to allergens. Similar immunity is involved in defence against these infectious agents but this immunity can be disturbed in asthmatic subjects; as seen with defects in immunoglobulin subclasses, disturbance in T lymphocyte function, monocytes and blood neutrophils. The determination of the genetic or acquired character of these disturbances is pre condition for the development of a therapeutic substitute. PMID- 1857825 TI - [The immunology of tuberculosis and human immunodeficiency virus]. AB - The mechanisms of humoral and cellular immunity in the body's defences against tuberculosis are reviewed in the light of recent fundamental works. Major progress has been made in understanding the structure of mycobacteria, in particular in those areas concerning antigenic determinants which may have diagnostic or therapeutic implications. The impact of the human immunodeficiency virus infection on the antituberculous defences is discussed, on the epidemiological aspects as well as clinical and physiopathological. PMID- 1857826 TI - [Cystic fibrosis and bronchial hyper-reactivity]. AB - An increased airway responsiveness to inhaled nonspecific stimuli has been often observed in cystic fibrosis patients. But bronchial hyperreactivity in such patients is due, in most cases, to damaged bronchial mucosa rather than to coexistent asthma, and it remains under question whether or not bronchodilators are of help in cystic fibrosis. Indeed some authors reported adverse effects after inhalation of beta-mimetic drugs. This behavior seems to be due to an "instability" of the bronchial walls in cystic fibrosis. Nevertheless other studies showed that bronchodilators could be of help when administered in some cases and during definite periods in the evolution of the disease. Indeed, variability in responsiveness to bronchodilator drugs is one of the features of cystic fibrosis and therapy must be adjusted to this variability in every patient. In any way, pulmonary functional tests must be performed before and after administration of a bronchodilator drug and before beginning such therapy. PMID- 1857827 TI - [Talc therapy during thoracoscopy of pneumothorax due to rupture of the bullae in emphysema. A study of 71 cases]. AB - The treatment of pneumothorax for large emphysematous bullae is classically surgical. We report a study of 71 patients treated by pleural talc therapy using thoracoscopy with good or excellent long term results in 93% of cases at a cost of some minor side effects. These results were compared with other forms of medical treatment which were always less effective and with surgical techniques which had more severe side effects. These results enable us to stress the value of talc therapy using pleuroscopy in patients with respiratory failure. PMID- 1857828 TI - [Pulmonary infection with Mycobacterium szulgai]. AB - Mycobacterium szulgai is a newly recognised species of mycobacteria whose pathogenicity in man can only be confirmed following certain criteria. We report a new observation comprising three points of interest. M. szulgai appears to be directly responsible for pulmonary infection and the clinical and radiological progress is very rapid. The human disease probably comes from infected water in aquaria. We have reviewed other cases of M. szulgai in the literature and for two out of three amongst these there is pulmonary involvement resembling tuberculosis; in the other cases cutaneous disease, synovial disease and bone disease have been described. PMID- 1857829 TI - [Myocardial infarction and vinorelbine. Report of a case]. AB - The authors report a case of a patient dying as a result of a myocardial infarction which was probably related to the administration of vinorelbine, the vinca alkaloid recently introduced into the treatment of non small cell bronchial cancers. PMID- 1857830 TI - [Thrombo-embolic disease with antiphospholipid-type serum auto-antibodies]. AB - We report a case of thrombo-embolic disease in which we were able to detect the presence of serum antiphospholipid auto-antibodies. The existence of antiphospholipid auto-antibodies has already been described in cases of recurrent thrombo-embolism. The thrombogenic role is only partially explained, but would for the greater part be linked to an action on the fibrolytic activity of the vascular parietal wall. Amongst these antibodies one can find amongst others VDRL, antiprothrombinase and anticardiolipin. The association of other stigmata of auto immunity is not rare, especially disseminated lupus erythematosus (LED). When phospholipids are found in an isolated fashion in cases of recurrent thrombo embolism they produce the syndrome of antiphospholipids. The long term prognosis of this syndrome has not yet been established but the risk of a secondary systemic disease developing justifies a clinical follow up and regular blood checks. PMID- 1857831 TI - [Pulmonary siderosis and long-term respiratory risks of arc welders]. AB - Pulmonary siderosis and bronchial cancer are respiratory risks in the long term in arc welders. We report a case of siderosis discovered from radiological abnormalities in a patient of 56 who had been an arc welder for 30 years. An analysis of the broncho-alveolar lavage liquid and transbronchial biopsy confirmed an iron overload and revealed patchy interstitial fibrosis. The toxic risks in arc welders arise from the gaseous fumes produced and inhaled particles at the alveolar level. The pulmonary siderosis is currently considered as a simple pneumoconiosis with a good prognosis. Some recent studies suggest the possibility of a more serious outcome with fibrosis even in the absence of any associated silicosis. The risks of bronchial cancer seem to be principally linked to exposure to chrome. A better understanding of these risks could be furnished by data from epidemiological studies which are still lacking. PMID- 1857832 TI - [A new form of mushroom workers' lung]. AB - The authors describe a new form of mushroom workers' lung after assessing the clinical situation and also the results of an immunological study. The case was related to the mushroom Poria megalopora. A new antigen has been identified and also its domiciliary origin, thus the ubiquitous nature of the antigen contributes to the interest of the case reported. PMID- 1857833 TI - [Hypervasopressinism during tuberculous meningitis]. AB - In tuberculous meningitis there is a disturbance of control involving hyponatraemia and increased urinary elimination of antidiuretic hormone resulting in hypersecretion of vasopressin. This inappropriate secretion of antidiuretic hormone should not be confused with the Schwartz-Bartter syndrome, which is reserved for paraneoplastic syndromes. The pathophysiology remains poorly understood but its recognition in cases of lymphocytic meningitis is improved as the correct diagnosis has precise therapeutic implications. PMID- 1857834 TI - [Pulmonary varices]. PMID- 1857835 TI - [The results of a survey on the attitude of pneumonologists toward sleep apnea syndrome]. PMID- 1857836 TI - [The diagnosis of pulmonary embolism]. PMID- 1857837 TI - [The validity of the association between passive smoking and the risk of primary bronchial cancer]. PMID- 1857838 TI - [Surveillance of adverse reactions of drugs and monitoring of drug prescriptions as routine in hospital activities]. AB - Since January 1988 is taking place a multicentre experience on pharmaco epidemiology named ARIES (Adverse Reaction Identification Evaluation System), with two primary aims: surveillance of drug adverse reactions and monitoring of medical prescriptions. At present 5 departments of internal medicine are involved in the study. The factual cooperation of the departmental doctors depends on the evaluation of benefits and costs of the study. The benefits for doctor are: (a) the possibility of contributing to the research in a field which has not been systematically investigated in a hospital setting; b) the acquisition of skill in monitoring adverse reactions: to facilitate doctors cooperation an algorithm has been developed to select the events to be entered into the system; c) the possibility of evaluating and improving the prescription habits. At present, data on 9,000 patients and 60,000 prescriptions are available. As an example of utilization study, we report a research on antibiotics prescribed for bronchopneumonia in two departments involved in the ARIES project. The remarkable differences in the prescription settings lead to some rethinking on the strategies of such different prescription choices. In each department, the contribution of doctors is integrated by a monitor, entering additional information on drugs and patients into the system. Thanks to the cooperation of doctors and contribution of monitors, the pharmaco-epidemiology research may become a "normal" component of the hospital activities, thus allowing to systematically retrieve and process some basic knowledges, which are not routinely used, derived from the daily activity of the departmental doctor. PMID- 1857839 TI - [Topical intranasal cortisone therapy]. AB - Owing to improvements made during the last 15 years in the pathophysiological and pharmacological research, many new corticosteroids have been successfully experimented. They have high activity on the target organ and they are suitable for long term therapies since they have not any systemic and/or local side effects. Nowadays the topical intranasal corticosteroid therapy is indispensable for allergic rhinitis treatment and it is very useful for many nasal and bronchopulmonary diseases (some chronic rhinitis, nasal polyposis, bronchial asthma, chronic obstructive bronchopulmonary diseases). The authors use their personal experience and carefully review the literature to describe the general aspects (pharmacology, pharmacokinetics, toxicology, side effects and contraindications) and to analyze the single drugs currently used in Italy and abroad. Finally, they compare the efficacy of each topical intranasal glucocorticoid among themselves and with other drugs. PMID- 1857840 TI - [Heparin anticoagulant activity: new knowledge and future prospects]. AB - The present knowledge about the heparin molecular structure has been reported by current scientific literature and especially the relationship between structure and function. From the pharmacological point of view the authors suggest future lines of research in this field. The role of endothelial and the mechanisms of heparin removal from the circulation (saturation and desaturation) are analyzed. From the anticoagulation point of view the authors after the analysis of the anti thrombin III and anti-factor Xa activity, evaluate the heparin biological action on the platelets, complement, white blood cells. They also evaluate the questions collected to heparin use in non classical clinical situations, alternative routes of administration and new therapeutic and anticoagulant procedure; the association of prostacyclin together with heparin. PMID- 1857841 TI - [Mebendazole in the therapy of hydatidosis]. AB - The effectiveness of mebendazole as adjuvant treatment in hydatidosis was evaluated in 19 patients; 12 were treated both before and after surgery, 6 were not treated, one had primary treatment only, owing to the refuse of surgery. Mebendazole was administrated at the dosage of 30-50 mg/kg/day po for 30 days followed by a washout of 15 days, for a mean of 4 cycles (range 1-7) and 12 cycles (range 1-24) before and after surgery, respectively. Patients were monitored by total IgE, specific anti-echinococcus IgE and IgG, at diagnosis, just before surgery and thereafter every six months. Antibody titer decrease was observed soon after the first cycles of medical treatment before surgery, as well as a clear-cut drop after surgery, followed by a continuing decrease after the following cycles of mebendazole. Relapse of disease was observed in two patients only at one and two years after surgery respectively. These preliminary results seem to point out that mebendazole might play a role in the treatment of hydatidosis as adjuvant of surgical therapy. PMID- 1857842 TI - [Effects of simvastatin on atherogenic blood lipid pattern]. AB - The effect of a 6-month treatment with simvastatin, an HMG CoA-reductase inhibitor, on serum lipoprotein pattern was investigated in patients affected by primary hypercholesterolemia. After 4-6 weeks of lipid lowering diet, 46 patients showing serum cholesterol greater than 250 mg/dl and triglycerides less than 200 mg/dl were included in the study and treated with simvastatin (10-30 mg/day) plus diet. Serum total cholesterol, LDL-cholesterol, apolipoprotein B and triglycerides levels significantly decreased at the end of the follow-up (-27%, 33%, -22%, -26% respectively). Apolipoprotein A1 showed a significant increase as well as HDL-cholesterol, HDL3-cholesterol and apolipoprotein A1/B ratio. This study provides further findings on the simvastatin efficacy to normalize the lipoprotein pattern in primary hypercholesterolemia. PMID- 1857843 TI - [Naloxone and naltrexone in the therapy of advanced COPD]. AB - We report a patient with COPD and bullous emphysema treated with narcotic antagonists (naloxone and naltrexone) for severe respiratory failure, with hypoxemia and hypercapnia, non responding to traditional medical therapy. According to previous reports, this treatment was started while waiting for lung transplantation, and it improved clinical pattern and arterial blood gas levels. Though the patient died for left ventricular failure fifteen days after the beginning of therapy, we think that narcotic antagonists can be successfully administered in some patients with advanced stage COPD. PMID- 1857844 TI - Acute cholestatic hepatitis during simvastatin administration. AB - Simvastatin, recently introduced in clinical practice for pharmacological treatment of hypercholesterolemia, has been found to cause minor and reversible elevations of serum transaminases. We report a case of acute cholestatic hepatitis during simvastatin therapy. Clinical, biochemical, immunological, and histological findings were consistent with a simvastatin-induced liver damage through an immunological-mediated mechanism. This case suggests a careful monitoring of liver function tests during simvastatin therapy, and caution in continuing simvastatin administration when elevations of serum transaminases take place. PMID- 1857845 TI - [Cyclofenil-induced acute hepatitis. A retrospective diagnosis of a case during acute hepatitis B]. AB - We report a case of acute hepatitis due to cyclofenil retrospectively diagnosed during acute viral hepatitis (HBV). Hepatitis developed 3 months after the beginning of administration and was reversible after withdrawal of the drug. The case is documented on the basis of liver histology and the exclusion of other causes of acute hepatitis. PMID- 1857846 TI - Terlipressin-induced metabolic acidosis. AB - Vasopressin and its analogue terlipressin are potent vasoconstrictors which reduce mesenteric blood flow and have been used in the therapy of variceal hemorrhage. This vasoconstrictor effect applies on vascular beds throughout the body. Since in literature vasopressin is rarely described to determine lactic acidosis, we report of a patient in whom a severe metabolic (probably lactic) acidosis appeared, associated with terlipressin administration for bleeding esophageal varices. By exclusion, the temporal sequence with terlipressin therapy, the contemporary increase of arterial blood pressure and autoptic data in the case presented make likely a diagnosis of terlipressin-induced lactic acidosis. Because of the seriousness of metabolic acidosis observed in our patient we suggest a careful monitoring of acid-base parameters in patients under treatment with vasopressin analogues. PMID- 1857847 TI - [Clinical experiences with tenoxicam. Preliminary results of a multicenter study]. AB - Preliminary data concerning the efficacy and tolerability of tenoxicam in a large, multicenter Italian study are presented. In many centres 625 patients (31% of the total) have been evaluated: 283 patients with osteoarthrosis and 342 with extra-articular rheumatism completed the study. Efficacy of tenoxicam (20 mg/die) was stated as equivalent or superior to reference drugs (diclofenac 100 R, piroxicam 20 mg). Tolerability profile has been generally good; tenoxicam, in particular showed the lowest incidence of side effects (7.4%). PMID- 1857848 TI - [Bone mineral contents: relation to muscle force and fitness of menopausal women]. PMID- 1857849 TI - Helicobacter pylori in migrants. PMID- 1857850 TI - [Angiotensin-converting enzyme inhibitors]. PMID- 1857851 TI - [An Italian or European review?]. PMID- 1857852 TI - Use of nonpharmacological techniques to prevent chemotherapy-related nausea and vomiting. PMID- 1857853 TI - Sexuality: an unknown word for patients with a stoma? PMID- 1857854 TI - Cytokines and hematopoietins: physiology, pathophysiology, and potential as therapeutic agents. PMID- 1857855 TI - Hemopoietic growth factors in the treatment of acute leukemias and myelodysplastic syndromes. PMID- 1857856 TI - Recombinant human interleukin-3 in patients with hematopoietic failure. AB - Nine patients with bone marrow failure and prolonged severe cytopenias were treated with recombinant human interleukin-3 (rhIL-3) at doses ranging from 30 micrograms/m2 to 500 micrograms/m2. rhIL-3 was administered in a subcutaneous bolus injection daily for 15 days. Platelet counts increased by a mean of 6-fold (range: 1.3- to 14.3-fold) in five out of eight evaluable patients. Reticulocyte counts increased 2.9-fold in three patients, and neutrophil counts increased by a mean of 3.1-fold in all eight patients. Platelet transfusions could be discontinued after treatment with rhIL-3 in two out of three evaluable transfusion-dependent patients. Only mild side effects, mainly fever and headache, were observed. These results indicate that rhIL-3 functions as a multilineage hematopoietic growth factor in vivo in patients with secondary bone marrow failure. PMID- 1857857 TI - Recombinant human granulocyte-macrophage colony-stimulating factor for the intensification of cytostatic treatment in advanced cancer. PMID- 1857858 TI - Surgical experiences with 191 implanted venous Port-a-Cath systems. AB - The introduction of totally implantable catheter device has provided a simple, permanent and safe access to the vascular system. They have greatly improved the quality of life of the patients involved, whose activities, daily hygiene and bodily attractiveness remain practically unrestricted. To gain the greatest freedom from complications in the use of fully implantable catheter devices, the following requirements are important in to our experience: 1. Experience with only one kind of catheter system, irrespective of whether it is claimed to be the best, the simplest, or the cheapest. Various companies offer a variety of totally implantable catheter devices. Every system has its advantages and its disadvantages. However, each system also requires a considerable degree of surgical experience and experience in postoperative care and management to keep the complication rate as low as possible. Frequent changing to other systems does not enlarge the experience obtained. 2. The experience of the surgical team. In Basel catheter systems are implanted by three surgeons only. We are convinced that this contributes to our relatively low rate of complications. Brothers et al. (1988) also show that the rate of complications is inversely related to the experience of the surgeon involved. 3. The experience, commitment and training of the nursing staff responsible for the care and maintenance of the implanted catheter device. This care and maintenance of the implanted catheter device should start immediately after the surgical procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1857859 TI - Maintenance and care of patients with drug delivery systems. PMID- 1857860 TI - Implantable devices in patients with haematological diseases. PMID- 1857861 TI - Opiate-resistant pain: a therapeutic dilemma. PMID- 1857862 TI - Tumor anorexia: causes, assessment, treatment. PMID- 1857863 TI - Food service provisions for the cancer patient. PMID- 1857864 TI - Prevention of radiogenic side effects using glutamine-enriched elemental diets. PMID- 1857865 TI - Diet to prevent gastrointestinal cancer? PMID- 1857866 TI - Alternative dietary therapies in cancer patients. PMID- 1857867 TI - Psychological aspects of malnutrition in cancer patients. PMID- 1857868 TI - A model for the development of psychosocial interventions. PMID- 1857869 TI - Aspects of nonverbal communication. PMID- 1857870 TI - Alterations of host defenses: the key to the multifaceted spectrum of infections in immunocompromised patients. AB - Patients with cancer are subject to bacterial infections because of a variety of specific defects. Patients may suffer increased susceptibility to infection by virtue of the invasiveness and obstructiveness of their basic malignancy as well as because of malignant processes directly involved in the hematopoietic and lymphoid systems. Also, the potent therapeutic modalities useful in treating malignant disease carry with them an associated suppression of bone marrow and lymphoid functions which can also result in increased bacterial infection. Physicians caring for patients with cancer must be aware of the potential preventive measures, such as careful handwashing, use of laminar air flow units, partial gut decontamination, and possible use of vaccines and antibodies to minimize infection in their patients. PMID- 1857871 TI - Spectrum and treatment of bacterial infections in cancer patients with granulocytopenia. AB - Bacterial infections remain a frequent cause of morbidity and mortality in cancer patients with granulocytopenia. In recent years the proportion of patients with gram-positive infections, caused mainly by coagulase-negative staphylococci and viridans streptococci, has increased markedly in many institutions. The precise reasons for this recent change in the epidemiology of infection in cancer patients are as yet not fully ascertained. Although less prevalent, gram-negative infections are still the major threat, since they are associated with higher mortality. What constitutes the optimal empirical antibiotic therapy remains a controversial issue. One should however recognize that the results of one particular study may not be relevant to other institutions where the predominant pathogens and the pattern of antibiotic resistance may be different. In addition, the results of studies using various antibiotic regimens should be compared with caution. However, with these limitations in mind, the results of the most recently published studies support the following recommendations: in patients with nonmicrobiologically documented infections, monotherapy with a third generation cephalosporin or a carbapenem is a safe alternative to combination therapy. For gram-negative bacteremia, combined therapy with an extended-spectrum beta-lactam antibiotic and an aminoglycoside appears preferable. For gram positive infections, a specific anti-gram-positive antibiotic is not needed in every patient and can safely be added upon identification of the pathogen in those patients not responding to empirical therapy. PMID- 1857872 TI - Prevention of infections in granulocytopenic patients by fluorinated quinolones. PMID- 1857873 TI - Influence of infusion time on the acute toxicity of amphotericin B: results of a randomized double-blind study. PMID- 1857874 TI - New antiviral drugs for treatment of viral infections in immunocompromised patients. PMID- 1857875 TI - Effective pain control in cancer patients in the home care setting. PMID- 1857876 TI - Prevention, early detection, and management of oncologic emergencies. AB - The prevention and early detection of oncologic emergencies is critical in caring for the person with cancer. Although many will not develop an oncologic emergency during the course of their illness, the approach outlined in this paper will contribute significantly to the prevention and relief of suffering in those individuals who may develop them. PMID- 1857877 TI - Relief from respiratory distress in advanced cancer patients. PMID- 1857878 TI - Treatment and support in confusional states. PMID- 1857879 TI - Parental death: a preventive intervention. AB - The untimely death of a spouse and parent is extraordinarily painful and difficult. Whether a brief intervention such as the one we are exploring is enough to make a significant difference in the mourning process and future optimum survival has yet to be seen. To date we are gratified that the immediate response of most of the surviving spouses and children is that the intervention is a helpful experience. PMID- 1857880 TI - Is the therapeutic use of opioids adversely affected by prejudice and law? PMID- 1857881 TI - Optimising bereavement outcome: reading the road ahead. PMID- 1857882 TI - Rehabilitation of the person with cancer. PMID- 1857883 TI - Interdisciplinary rehabilitation of the laryngectomee. AB - It is to be hoped that human aspects have not been forgotten in spite of all these statistics. Behind all these numbers lie the personal fates of approximately 700 laryngectomees in Switzerland. The interview findings reflect their situation in life. In summary, we can say that: --Half of the laryngectomees lose their job and feel restricted in their daily lives; every third one mentions financial problems. --A third of the laryngectomees are totally or partly unsatisfied with the speech rehabilitation program. --There appear to be remarkable differences within the various language regions in Switzerland with regard to preparation for the operation, speech rehabilitation, and the current life situation of laryngectomees. From our study, we conclude that extensive medical, psychological, and social counseling and assistance for those affected is of great importance. Here we must especially mention the preparation of the patients and their relatives for the operation and its consequences. This should be the task not of one person but of an interdisciplinary team, including a logopedist, a social worker, and also another laryngectomee, with whom contact is often very valuable for the patient. Early speech therapy, reintegration into working life, and improvement of financial status are further factors of great importance. PMID- 1857884 TI - Treatment of severe cancer pain by continuous infusion of subcutaneous opioids. PMID- 1857885 TI - Coping with cancer pain. PMID- 1857886 TI - Controlling emesis in patients receiving cancer chemotherapy. PMID- 1857887 TI - Cancer pain: pathogenesis, therapy, and assessment. PMID- 1857888 TI - Present role of corticosteroids as antiemetics. PMID- 1857889 TI - Simulated weightlessness and bone metabolism: impairment of glucose consumption in bone tissue. AB - The effect of simulated weightlessness on bone glucose consumption was investigated in skeletal unloading for up to 4 days. Skeletal unloading was designed using the model of hind-limb hang in rats. Femoral-diaphyseal fragments obtained from rats bred with skeletal unloading were cultured for 24 h at 37 degrees C in 5% CO2/95% air in Dulbecco's Modified Eagle Medium (high glucose, 4.5 g/dl). The consumption of medium glucose by bone tissues was significantly decreased by skeletal unloading for 2 and 4 days, while the production of lactic acid from bone tissues was not significantly altered. In addition, adenosine triphosphate (ATP) content in the cultured bone was significantly decreased by skeletal unloading. The presence of calcitonin (synthetic [Asu1,7] eel, 3 and 30 nM) fairly restored bone glucose consumption impaired by skeletal unloading. However, the effect of insulin (1 and 10 nM) on bone glucose consumption and ATP content was not seen in the bone tissues with skeletal unloading. These results suggest that the sensitivity of bone response for insulin action is reteriorated by skeletal unloading. PMID- 1857890 TI - Simulated weightlessness and bone metabolism: impairment of insulin effect on alkaline phosphatase activity in bone tissue. AB - The effect of simulated weightlessness on bone alkaline phosphatase was investigated after skeletal unloading for up to 4 days. The skeletal unloading was designed by using the model of hindlimb hang in rats. The femoral-diaphyseal fragments obtained from rats bred with skeletal unloading were cultured for 24 h at 37 degrees C in 5% CO2/95% air in Dulbecco's Modified Eagle Medium (high glucose). The bone alkaline and acid phosphatase activity were significantly decreased by skeletal unloading. When the bone tissue was cultured with synthetic [Asu1,7] eel calcitonin (3 and 30 nM), the hormone caused a significant increase of alkaline phosphatase activity in the bone tissues from rats with normal and skeletal-unloading. In culture with insulin (1.0 and 10 nM), skeletal unloading impaired the effect on insulin to increase bone alkaline phosphatase activity. Meanwhile, the culture with zinc sulfate (10 and 100 microM), which can increase bone protein synthesis, caused a remarkable elevation of alkaline phosphatase activity in the bone tissues form rats with normal and skeletal-unloading. Insulin (10 nM) did not alter the zinc effect. These findings suggest that the skeletal unloading with hindlimb hang causes the impairment of insulin's effect to increase alkaline phosphatase activity in the femoral diaphysis of rats, although the effects of calcitonin and zinc were not altered. PMID- 1857891 TI - Obese Zucker rat: potential role of intraglomerular proteolytic enzymes in the development of glomerulosclerosis. AB - The obese Zucker rat is a classic model of non-immune-mediated spontaneous focal glomerulosclerosis. An early morphological hallmark of glomerular damage in the obese Zucker rat is a mesangial expansion, which precedes and mediates the development of glomerular damage in these animals. This study was designed to investigate whether there might be a reduced activity of glomerular proteinases in kidneys of obese Zucker rats, thereby being involved in the pathogenesis of mesangial expansion, which is mainly due to protein overloading. In fact, we found a decreased proteinase activity in ultrasonically destroyed isolated glomeruli obtained by a differential sieving technique in obese Zucker rats compared with their lean littermates. This held true at acid as well as at neutral pH and could be confirmed when proteinase activity was related to DNA instead of protein. When investigating the glomerular cathepsin B content--this is a lysosomal enzyme with acid pH optimum, which is involved in the degradation of glomerular structural as well as filtered plasma proteins--we found a significantly increased level in the kidneys of obese Zucker rats. Hence, the intraglomerular proteinase activity is reduced in the face of enhanced glomerular content of at least lysosomal proteinases. The underlying reason for this depressed activity remains to be established. We propose that reduced activities of intraglomerular proteinases may be important in the pathogenesis of mesangial matrix expansion in obese Zucker rats, an important initiating hallmark of glomerulosclerosis in this model. PMID- 1857892 TI - Effect of estrogen on bone metabolism in tissue culture: enhancement of the steroid effect by zinc. AB - The present investigation was undertaken to clarify the effect of estrogen (17 beta-estradiol) on bone metabolism in tissue culture. Calvariae were removed from weanling rats (3-week-old females) and cultured for periods up to 96 h in Dulbecco's Modified Eagle Medium (high glucose, 4500 mg/dl) supplemented with antibiotics and bovine serum albumin. The experimental cultures contained 10(-10) to 10(-8) M estrogen. All cultures were incubated at 37 degrees C in 5% CO2/95% air. Bone calcium content was significantly increased by the presence of 10(-10) to 10(-8) M estrogen. The steroid (10(-10) to 10(-8) M) also significantly increased alkaline phosphatase activity in the bone, whereas it did not significantly alter acid phosphatase activity. No appreciable effect on bone alkaline phosphatase activity was produced with 17 alpha-estradiol (10(-9) and 10(-8) M). Tamoxifen (10(-6) M), an anti-estrogen, completely blocked the effect of estrogen (10(-9) M) of increasing bone alkaline phosphatase activity. Furthermore, bone DNA content was significantly increased by 10(-10) to 10(-8) M estrogen. Meanwhile, the presence of 10(-4) M zinc, which can stimulate bone protein synthesis, significantly enhanced the effect of 10(-9) M estrogen to increase DNA content in rat calvaria, while the metal did not enhance the steroid effect on bone calcium content and alkaline phosphatase activity. The presence of 10(-7) M cycloheximide completely prevented the stimulatory effect of estrogen (10(-9) M) on calcium content, alkaline phosphatase activity, and DNA content in rat calvaria. The present study demonstrates that estrogen has a direct stimulatory effect on bone metabolism in tissue culture and that zinc can enhance the steroid effect on bone DNA. PMID- 1857893 TI - Extending effects of phospholipids, cholesterol, and ethanolamines on survival of adult rat hepatocytes in serum-free primary culture. AB - In a serum-free primary culture, membrane lipids, such as phosphatidylethanolamine, phosphatidylcholine, or cholesterol, effectively prolonged the survival of adult rat hepatocytes. These lipids effectively prevented hepatocytes from morphologic degeneration observed in control cultures, such as enlargement of cell surface, degranulation of cytoplasm, and multinucleation. The maintenance effect of phospholipid precursors, ethanolamine, or phosphoethanolamine on the primary-cultured hepatocytes was similar to that of phospholipids. These effects appear to be due to stabilization of the plasma membrane. PMID- 1857894 TI - Oxidatively modified human low-density lipoprotein stimulates leukocyte adherence to the microvascular endothelium in vivo. AB - In vitro studies indicate that oxidatively modified low-density lipoprotein (oxLDL) promotes leukocyte sticking to the vascular endothelium, a constant feature of early atherogenesis. Using intravital fluorescence microscopy in the dorsal skinfold chamber model in hamsters, we investigated whether systemic administration of human LDL, oxidized by Cu2+, elicited leukocyte/endothelium interaction in vivo. While no effect was seen after injection of native LDL, oxLDL administration resulted in an immediate induction of leukocyte rolling along the microvascular endothelium and subsequent firm sticking to the wall of postcapillary venules as well as arterioles. The presented model may provide an alternative experimental approach to long-term feeding studies with atherogenic diets for the in vivo investigation of leukocyte/endothelium interaction in early atherogenesis. PMID- 1857895 TI - Intracranial pressure changes following middle cerebral artery occlusion in rats. AB - Prolonged recording of intracranial pressure (ICP) was performed on rats subjected to middle cerebral artery (MCA) occlusion. ICP was repeatedly recorded before and after occlusion of the vessel via a narrow catheter placed in the cisterna magna. MCA occlusion was followed by an increase in ICP, and a pressure peak occurred after 12-24 h in all animals. Subsequently, essentially two patterns of ICP changes were observed. These seemed to be related to the severity of neurological deficits and extension of the infarct area. In the most severely affected animals, raised ICP was noted throughout the 1st week after MCA occlusion; in rats with reversible neurological deficits, ICP returned to normal values after the first peak at 12-24 h. The present investigation shows that prolonged ICP recording is feasible in MCA-occluded rats. The MCA occlusion model in rats is well characterized. Thus, ICP registration can be used in conjunction with other methods for evaluating treatment against increased ICP. PMID- 1857896 TI - Ronald Glenn Michels 1943-1991. PMID- 1857897 TI - Ronald Glenn Michels 1943-1991. PMID- 1857898 TI - [Epidemiology of hypertension in old age]. AB - This article shows the epidemiologic dimension of hypertension in the elderly. The number of the elderly in Switzerland is expected to increase significantly until the first decades of the new millenium; therefore, geriatric medicine and hypertension in the elderly in particular will become even more important than it is at present. Cardiovascular disease is blamed for a major share of prematurely lost years of life. In the past few years the age-standardized mortality of ischaemic heart disease has declined in Switzerland, while the rate for cerebrovascular disease has gone down earlier. The project MONICA may explain the reasons for these trends. Hypertension shows also in Switzerland a high prevalence, which even increases in older age groups. In the Framingham cohort study (USA) it was shown that hypertension is the most important risk factor for cardiovascular morbidity and mortalitity in the elderly. This is particularly true for the most common form of hypertension in the elderly, the isolated systolic hypertension. Because of the described demographic development, hypertension in the elderly, its prevention, diagnosis and management will become even more significant. PMID- 1857899 TI - [Hypertension in the aged: how to assess it?]. AB - In the elderly hypertensive patient several of the basic procedures during evaluation should be repeated or performed with particular care. Most importantly multiple pressure measurements should be taken repeatedly, orthostatic reactions have to be sought by taking the blood pressure in the standing and lying patient and the carotid vessels have to be auscultated. If a carotid occlusion or stenosis is suspected, a Doppler ultrasound study is indicated prior to therapy. Generalized arteriosclerosis is probably rarely the cause of so called pseudohypertension. It should be considered when strikingly high blood pressure values contrast with clinical signs of low blood pressure. Finally if hypertension develops rapidly in an elderly patient renal arterial stenosis should be suspected. PMID- 1857900 TI - [Hypertension in the aged: when to treat it?]. AB - According to several recent studies prevalence of hypertension in the elderly ranges from 40 to 60%. Both, systolic as well as diastolic increase of blood pressure must be regarded as individual cardiovascular risk factors. Treatment of hypertension in the elderly gains special importance in the presence of additional risk factors. There is no doubt about the benefit of antihypertensive therapy when the diastolic value amounts to 100 mmHg and more. No reliable data exist so far on a beneficial effect of the treatment of systolic hypertension. Whether hypertensive patients older than 80 years and patients with only marginal increases of blood pressure benefit from antihypertensive treatment has not been proven by current studies. If the patient's anamnesis includes cerebral stroke a cautious antihypertensive therapy may reduce cardial insufficiency without increasing the risk for another apoplexia. PMID- 1857901 TI - [ACE inhibitors in the treatment of hypertension in elderly patients]. AB - Recent epidemiological studies clearly indicate that blood pressure rises with age and that hypertension remains a major risk factor for cardiovascular morbidity and mortality in the elderly. An accurate antihypertensive therapy reduces in these patients the incidence of stroke and heart failure. Because of their clinical efficiency and good therapeutic tolerance, the angiotensin converting enzyme (ACE) inhibitors are first-line drugs for the treatment of elderly hypertensive patients. ACE inhibitions is expected to normalize blood pressure in approximately 40-60% of the patients. When needed, they can be combined with other drugs of different antihypertensive properties. In these cases, the most rational combination therapy consists of an ACE inhibitor with a diuretic or a calcium antagonist. PMID- 1857902 TI - [Combined orthopedic-orthodontic treatment of Class II]. PMID- 1857903 TI - [Precautions in the use of facebows]. PMID- 1857904 TI - [Surface treatment of mineralized tissue: different approaches and prospects]. AB - This paper review the effects of orthophosphoric acid and other acidic agents on dental enamel. The effects of other treatments such as proteolytic agents or of mixture able to remove the lipids are also described. Specific problems are related to the dentine treatment. Acids and chelators should be avoided, because of the dentine tubules, the odontoblasts and pulp. We review also the problem of the smear layer, the surface of the carious dentine and the consequences for dental treatment. Researches which are still in progress are reported including the use of enzymes and alcali gels submitted to feeble electrolysis, this latter being able to prepare dentine, cementum and bone surfaces in order to increase the adhesion of biomaterials. PMID- 1857905 TI - [New Edgewise has arrived... (2)]. PMID- 1857906 TI - [An indirect bonding technique]. PMID- 1857907 TI - [Direct bonding with photopolymerization in straight-wire technique]. PMID- 1857908 TI - [A computerized management system or how to computerize your office]. PMID- 1857909 TI - Periodontal therapy for patients 65 years and older. PMID- 1857910 TI - Elective surgery in older persons. PMID- 1857911 TI - Surgery in the elderly. PMID- 1857912 TI - The post-operative care of the older patient: the geriatric and rehabilitation perspective. AB - As the population of our nation and our state grows older operative procedures will be performed at increasing rates on older patients. Unique aspects of older persons and the conditions with which they are afflicted place them at high risk for loss of function, medical complications, and surgical complications in the perioperative period. Only by conducting comprehensive preoperative assessments, establishing appropriate goals, maintaining meticulous perioperative care and beginning rehabilitation early will it be possible to reduce these risks and maximize the functional outcome for the older surgical patient. PMID- 1857913 TI - Trauma care for the elderly? AB - The enormous consumption of health-care resources by bluntly injured elderly patients can be justified if their outcome after trauma is good. In this series, 89% of injured elderly patients ultimately returned to their homes, either independent of (57%) or dependent on (32%) outside help. Factors contributing to increased mortality in such patients included age, injury severity, and the presence or absence of cardiac and septic complications. A Geriatric Trauma Survival Score (GTSS) was devised that predicted the likelihood of mortality in these patients. Finally, study of reimbursement indicated that Medicare does not adequately reimburse hospitals for the enormous cost of providing elderly trauma care. PMID- 1857914 TI - The ethical responsibility of surgeons in conflicts with patients or their surrogates about treatment. PMID- 1857915 TI - Should practicing physicians be routinely tested for the AIDS virus? PMID- 1857916 TI - [Somatosensory evoked potentials after stimulation of the posterior tibial nerve in multiple sclerosis: comparative analysis with other modalities of evoked response and magnetic resonance]. AB - Electrophysiological tests have proved to be a valuable method in assessing multiple sclerosis (MS) patients. In the last few years, scalp recorded short latency somatosensory evoked potentials to stimulation of nerves in the "lower extremity" have been more and more extensively employed. Some studies have aimed at comparing the sensitivity of MR imaging and multimodality evoked potentials, with somewhat conflicting results. In the present study posterior tibial nerve somatosensory evoked potentials (ptnSEPs) were performed in 29 MS patients with the aim to investigate the ability in revealing spinal cord conduction abnormalities and the sensitivity towards other evoked potentials and MR in MS. ptnSEPs showed a high percentage of abnormalities which did not significantly differ from that of visual evoked potentials; moreover in conjunction with median nerve SEPs can be used to localize thoracic or lumbar cord demielinating lesions, not evidenced on MR imaging. These results confirm that ptnSEPs, although non specific and crude in terms of precise localization, are a sensitive tool in detecting lesions, even subclinical, in MS patients. Moreover in anatomic regions like spinal cord where MR imaging is not very sensitive because the lower signal to-noise ratio, they represent the only method available for demonstrating lesions. PMID- 1857917 TI - HLA antigens and multiple sclerosis in the Province of Ferrara, northern-Italy: a community-based study. AB - The association between Multiple Sclerosis (MS) and DR2 HLA antigen is well known in Caucasoids. In the past few years a significant correlation has been found between DQwl and MS in North-East Scotland and in several other countries. In previous HLA studies in Italian MS patients, a lack of any association or an increased frequency of DR2 have been observed; however, the results of most Italian surveys derive from heterogeneous sample of affected individuals. This study was carried out in a homogeneous population of patients living in and originating from the province of Ferrara, Northern-Italy. Among the prevalence cases, 116, indigenous, unrelated patients, were typed for HLA-A-B, -DR and DQ antigens. The comparisons with 185 healthy individuals, originating from the same area, revealed an increased prevalence of DR2 antigen in Ferrara MS patients. This antigen does not appear to be related to the clinical variables of the disease. PMID- 1857918 TI - [A case of polymyositis in autoimmune thyroiditis with hyperthyroidism]. AB - A young woman, during an autoimmune thyroiditis with hyperthyroidism, suffered from progressive proximal weakness at her four limbs. The diagnosis of a concomitant polymyositis was indicated by a marked increase of plasma CPK, myopathic findings at EMG and a clearcut picture of inflammatory alterations at muscle biopsy. Steroid therapy brought a full recovery of both thyroid and muscular symptoms. In the following months, the patient suffered from a second episode of thyroiditis and subsequently from another poussee of polymyositis. The possible pathogenesis underlying the unusual association of an autoimmune thyroiditis with a polymyositis is discussed. PMID- 1857919 TI - [Epidemiologic study of epilepsy in the population of Este-Montagnana (U.L.S.S. 22-Veneto Region)]. AB - Epidemiological data of the U.L.S.S. n. 22 of Este-Montagnana (PD) show a prevalence of Epilepsy of 5.94%. These data are referred to an observation period of ten years (1978-1987) and confirm the results of major epidemiological trials in U.K. and U.S.A. Distribution by sex and types of crises is the same. The Authors underline the importance of alcohol-related crises; however this is not yet confirmed by precise parallel data. PMID- 1857920 TI - [Mechanisms of muscular fatigue]. AB - According to Merton (1954), Bigland-Ritchie (1978), Edwards (1981) and De Luca (1984), two groups of mechanisms, central and peripheral, may be distinguished in physiopathology of fatigue process. Central mechanisms are related to subjective phenomena, like fatigue sensation or motivation, and to objective aspects as spatial and temporal motoneurones recruitment. PMID- 1857921 TI - Self intra-cavernous injections as a successful treatment in pure neurogenic impotence. AB - The aim of our research is to investigate the success of the vasoactive intracavernous therapy in subjects suffering impotence only on a neurological basis. We have submitted 50 subjects to a multisciplinary study including P.B.P.I., intracavernous minitest plus V.S.S., M.M.P.I., B.C.R. latency, duration, aspect and an hormonal screening (SH, LH, PRL, F. TEST, 17 BE2). The patients, or their partners, were instructed in the technique of self intracavernous injection (S.I.C.I.) of vasoactive drugs. Papaverine alone was given to 37 patients in a mean dose of 20.8 +/- 11.7 mg. Other 13 patients were treated with papaverine plus phentolamine in order to obtain a full erection. Comprehensive results of the treatment were judged at 80% effective: only 10 patients discontinued self injection treatment, unable to perform this technique properly. PMID- 1857922 TI - [Clinical and neurophysiologic study of Guillain Barre syndrome: results of therapy with plasmapheresis]. AB - The Guillain Barre poliradicoloneuritis shows a high incidence of permanent sequelae and exitus. Recently the plasmapheresis has been applied in the acute stage with a beneficial effect to the rapidity and the degree of the recovery. In the present study the results obtained in a group of patients with Guillain Barre of maximal severity are reported. All the patients have received plasmapheresis (3-5 exchanges) in the first days of the disease. Eventual side effects during the procedure have been evaluated together to the neurophysiological findings. The recovery has been evaluated in the brief and in the long term. From this study the efficacy of the plasmapheresis in Guillain Barre poliradicoloneuritis is confirmed. Furthermore a correlation has been evidenced between the amplitude of the muscular potential (CMAP) registered in the acute phase and the prognosis of the illness. PMID- 1857923 TI - Hemichorea-hemiballism and anosognosia following a contralateral infarction of the caudate nucleus and anterior limb of the internal capsule. AB - The authors describe a patient who experienced the sudden occurrence of hemicorea hemiballism on the left side of the body and the contemporary agnosia of it. An unenhanced CT-scan disclosed an ischemic lesion involving the head of the caudate nucleus and of the anterior limb of the internal capsule of the contralateral hemisphere. The authors discuss the possible pathophysiologic mechanisms explaining the rare association of these two symptoms and suggest that the involvement of the pyramidal tract in the internal capsule usually does not allow hyperkinesis to manifest itself. PMID- 1857924 TI - [Respiratory distress in newborn infants. Positive diagnosis, principles of the emergency treatment]. PMID- 1857925 TI - [Physiology of tendon and physiopathology of tendinitis]. AB - Despite the histological knowledge acquired from light and electron microscopy and the deeper studies devoted to the composition of tendons, we are still unable to draw practical conclusions concerning the treatment of tendinitis. Experimental in vivo studies and biochemical studies are still too far from physiological conditions to be useful in the traumatology of tendons. They have, however, the merit to provide better theoretical basis and to persuade doctors specialized in sport not to disregard these date. PMID- 1857926 TI - [Achilles tendinitis]. AB - Achilles tendinitis is particularly frequent in athletes. In fact, this entity is made up of various anatomical lesions located in Achilles tendon or at the point where it is attached to the calcaneum. The diagnosis is basically clinical, and it is confirmed by carefully selected paraclinical examinations. Management essentially relies on rest associated with adequate physiotherapy and, when required, with other adjuvant treatments. Management also rests on the prevention of recurrences and on the suppression of the frequently found sport-related causal agent. Surgical treatment is seldom indicated, and only when medical treatment has failed, usually in high-level athletes. PMID- 1857927 TI - [Tennis elbow]. AB - Tennis elbow is most often due to a tendinitis of the extensor carpi radialis brevis, and occasionally of the extensor digitorum. Pain felt at the outer aspect of the elbow, is elicited by grasping. Passive movements are painless, and of full range, excepted for extension, and varus strain tested in slight flexion. Isometric contraction of all the muscles controlling the joint are painless, excepted resisted extension of the wrist. The most usual painful spots lay on the lateral epicondyle, or lower on the common tendon. Diagnosis is confirmed when signs disappear immediately after a correct injection of lignocaine, and persist at least 3 Weeks if a corticoid is added. The two outstanding differential diagnoses are internal derangement of the humero-radial joint, and entrapment of the sensory branch of the radial nerve. Many treatments are indicated. In a series of 58 cases, cervical manipulations give in most cases only a temporary relief; deep transverse massage applied on the tendon below the epicondyle, gives in a series of 131 cases good and excellent results in 63% of the cases. In a series of 257 cases, injections of corticoids gives full relief in all cases, but the rate of recurrences is 66.7%, although 67% of those recur only once or twice. Percutaneous tenotomy performed only in patients recurring after temporary cure, drops the rate of recurrences to 13%. The last alternative is open surgery, releasing the common tendon. PMID- 1857928 TI - [Tendinitis of the knee]. AB - The diagnostic criteria for tendinitis of the knee are: (1) strict localization of the pain in the whole length of the tendon from its body to its end; (2) recrudescence of pain during movements that stretch or rub the tendon, and (3) positive local anaesthesia test if needed. Only this approach makes it possible not to miss a tendinitis of the extensor system in a so-called femoro-patellar syndrome, or to misdiagnose a tendinitis of the sartorius, gracilis and semitendinosus muscles when confronted with an osteoarticular pathology of the medial femoro-tibial compartment. PMID- 1857929 TI - [Tendinitis of the foot]. AB - Tendinitis in the ankle and foot is frequent. It is due to overwork, relative senescence or rheumatoid inflammation. Damages are graded from isolated lesions of the sheath to rupture of the tendon. The diagnosis, at least anatomical, is facilitated by the superficiality of the tendons and by good anatomico-functional knowledge. Treatment rules cannot really be established. Surgery should remain wide open. The foot should always be the best static and dynamic conditions, and this can be achieved by possible plantar ortheses and by the quality of footwear. PMID- 1857930 TI - [Tendinitis of the hip region]. AB - Tendinitis and bursitis are less common around the hip than around the shoulder. Nevertheless, they must be recognized to avoid unnecessary and costly diagnostic errors. Their various clinical forms are studied in detail. Tendino-bursitis of the gluteus medius muscle is the most frequent in its subacute form, but it is rare in its acute, pseudo-gouty form. Calcification of the reflected tendon of the rectus femoris muscle often closely resembles arthritis of the hip. Synovial cysts of the psoas bursa and rupture of the gluteus medius tendon are rare but must be known. Local injections of corticosteroids play an important part in the treatment of these diseases. PMID- 1857931 TI - [Localization of the spinal muscular atrophy gene by reverse genetic methods. Prospect of a gene on chromosome 5]. PMID- 1857932 TI - [Epidermotropic T-cell lymphoma: a large variety of syndromes and prognosis]. PMID- 1857933 TI - [Acoustic oto-emissions. Value in audiology in children]. PMID- 1857934 TI - [Fractures of the lower end of humerus in children. Diagnosis, complications, principles of the treatment]. PMID- 1857935 TI - [Schizophrenia syndromes. Diagnosis, development, principles of the treatment]. PMID- 1857936 TI - [Epidemiology of collective infections and toxic-infections of food or water origin. Modalities of survey in front of outbreak]. PMID- 1857937 TI - [Tobacco smoking (1). Epidemiology of tobacco smoking, of diseases bound to tobacco. Consequences on the public health, prevention]. PMID- 1857938 TI - [Battered children. Diagnosis, medico-legal management]. PMID- 1857939 TI - [Medical penal, civil, administrative and disciplinary responsibility. Definition and elementary notions]. PMID- 1857940 TI - [Complications of acute appendicitis. Diagnosis, principles of the treatment]. PMID- 1857941 TI - [Superficial adenopathies. Diagnosis orientation]. PMID- 1857942 TI - [Thrombopenia. Diagnostic orientation]. PMID- 1857943 TI - [Cerebrotendinous xanthomatosis]. AB - Cerebrotendinous xanthomatosis (CTX) is a rare lipid storage disorder due to an autosomal-recessive inherited defect of the hepatic mitochondrial steroid 26 hydroxylase. The resultant reduced biosynthesis of cholic and especially chenodeoxycholic acid and the increased production and accumulation of cholestanol and cholesterol in most tissues is described and pathogenetic aspects as well as typical pathological findings are discussed. In the light of three personal observations the clinical symptoms and the results of auxiliary investigations are discussed and compared with the literature. The suspected diagnosis of CTX may be confirmed by demonstration of a pathologically elevated concentration of cholestanol or biliary alcohols in serum and urine respectively. The chronically progressive neurologic deficit can be halted or is in some cases partially reversible by treatment with chenodeoxycholic acid. Therefore, early diagnosis is mandatory and CTX should be considered in every patient presenting with intellectual impairment, spastic-ataxic signs, juvenile cataracts and tendon xanthomas. PMID- 1857944 TI - [Incidence and prognostic significance of positive blood cultures in neonatal and pediatric intensive care]. AB - The incidence and prognostic importance of positive blood cultures were evaluated over a two-year period (1986/87) in 1371 admissions to a multi-disciplinary neonatal and pediatric intensive care unit (ICU). Blood cultures were performed in 439 patients of which 80 cultures were positive. Septicemia was confirmed in 70 cases, the 10 remaining cases being classified as contamination or bacteremia. The incidence of nosocomial, ICU-acquired septicemia was low (7/70). The major causative organisms of sepsis were those commonly encountered in neonatal and pediatric infections, including Haemophilus influenzae (37), Escherichia coli (11, Neisseria meningitidis (9) and group B streptococci (3). Typically nosocomial organisms were rare. In the group of 70 septicemic cases, multiple organ system failure was diagnosed in 23 patients. Nine died, most often due to irreversible septic shock (13% mortality). In order to avoid a selection bias, all admissions were examined for the presence of sepsis syndrome (clinical signs of sepsis with negative blood cultures). Out of 21 such patients, three died. The results suggest that in comparison to intensive care in adults the following conclusions may be drawn: (1) sepsis with positive blood cultures plays a minor role at our unit; (2) the rate of ICU-acquired septicemia is low (10% of all cases of sepsis with positive blood culture); and (3) the prognostic bearing of a positive blood culture in patients with septic signs is not too unfavourable (87% survival rate). PMID- 1857945 TI - [Aplastic anemia combined with an autoimmune disease (eosinophilic fasciitis or glomerulonephritis)]. AB - We describe 3 patients with aplastic anemia and an autoimmune disease. Two had eosinophilic fasciitis and 1 glomerulonephritis. In all patients both diseases were successfully treated by immunosuppressive therapy. Pathophysiological aspects of this association are discussed. PMID- 1857946 TI - [Long-term therapy of Menetrier disease using ranitidine and pirenzepine]. AB - A 22-year-old woman with hypertrophic protein-losing gastropathy (Menetrier's disease) is described. During treatment with ranitidine (Zantic) and pirenzepine (Gastrozepin) the gastric mucosa and protein loss were normalized within 4 years. Clinical and histological remission has now been observed for 5 and 3 years respectively. In a 57-year-old woman with hypertrophic gastropathy, 8 months' treatment with ranitidine and pirenzepine was associated with decrease in protein loss and improvement of the histological appearance of the gastric mucosa after one year. Long-term treatment of hypertrophic gastropathy with ranitidine and/or pirenzepine should, therefore, be considered in such cases instead of gastrectomy. PMID- 1857947 TI - [Ultrasonic study of gastric emptying of various oral rehydration solutions]. AB - Gastric emptying of 4 different oral rehydration solutions was investigated by ultrasound in 7 healthy volunteers in a randomized double-blind study. The final gastric emptying times were 32.9 +/- 4.72 minutes for the glycine solution, 55.1 +/- 9.85 minutes for the glucose (WHO) solution. 60.8 +/- 11.58 minutes for the polycose solution and 58.6 +/- 10.12 minutes for the rice-flour solution (p less than 0.05). Gastric emptying times showed considerable person-to-person variability. Based on identical gallbladder volumes before and 60 minutes after ingestion of the rehydration solutions, there was no indication of cholecystokinin stimulation by any of the solutions tested. PMID- 1857948 TI - [Lateral intra- and extraforaminal lumbar disk hernia: clinical aspects and therapy]. AB - Lateral lumbar disc herniations in or beyond the intervertebral foramen account for nearly 10% of all lumbar herniations. They affect the nerve root exiting at the same level. Such a lateral herniation of disc L4, for example, would impinge on nerve root L4, while a common herniation inside the spinal canal would compromise root L5. Myelography most often provides false-negative results. High resolution CT scanning is completely accurate in demonstrating these lesions and therefore is considered the diagnostic method of choice. We review the anatomo pathological and clinical features and propose guidelines for radiological examination of these herniations. Finally, the lateral microsurgical approach to the intervertebral foramen is described. It permits exposure of the lateral disc prolapse without opening the spinal canal or performing facetectomy. PMID- 1857949 TI - [Barbiturate coma in the treatment of refractory status epilepticus in adults. Usefulness of continuous electroencephalography in intensive care]. AB - Status epilepticus represents one of the most frequent neurological reasons for admission to the intensive care ward. If it resists well-managed treatment, more aggressive measures must be taken. We report 3 such situations in which patients were treated by barbiturate coma under continuous electroencephalographic monitoring. On the basis of this experience we attempt to elaborate guidelines for the use of this technique. PMID- 1857950 TI - [Eosinophilic pleuritis and hepatopathy under trimipramine therapy]. AB - A case of allergic reaction under treatment with a tricyclic drug, trimipramine, is described. The clinical manifestation was an acute, influenza-like syndrome with eosinophilic pleurisy and involvement of liver function. This case is compared with allergic reactions under antidepressant treatment described in the literature. The combination of pulmonary and hepatic involvement in an allergic reaction is not unusual, but has not thus far been described for tricyclic antidepressants. The importance of laboratory investigations during antidepressant therapy is emphasized. PMID- 1857951 TI - [Ischemic colitis. Results of conservative treatment]. AB - 34 consecutive patients were admitted for ischemic colitis confirmed by colonoscopy, contrast enema, laparotomy, and/or post-mortem between 1984 and 1988. 13 underwent excisional surgery, usually at an early stage, because of acute abdomen. This study is devoted to the remaining 21 patients (62%), i.e. nearly two thirds of the whole series, who were treated conservatively (intravenous hydration and antibiotics). Our results suggest that (1) ischemic colitis usually affects elderly patients in whom an underlying cardiovascular disease is seldom found; (2) the right colon is infrequently involved, and (3) outcome is generally favorable in the absence of superimposed major pathology or of peritoneal signs which would require surgical exploration. PMID- 1857952 TI - [Surgical significance of intestinal non-rotation in adults]. AB - Intestinal non-rotation has been recognized as a cause of obstruction in neonates and children. It is very rarely seen in the adult and assumes surgical significance owing to the potential risk of midgut or ileocecal volvulus. However, it can also cause significant intermittent abdominal pain in the adult. We describe six personally observed patients with this malformation and analyze 38 case reports published in the English and German literature since 1923. We establish that in the acute symptomatic form only emergency laparotomy can provide the correct diagnosis and decrease the risk of bowel disturbance. In the chronic forms, barium studies of the whole intestinal tract reveal varying degrees of midgut malrotation and the non-rotation is confirmed in each case. Also in these forms, exploratory laparotomy with a consequent staging of the abdominal situs is to be recommended. In the operation described by Ladd the ascending colon is sutured at the colon descendens and sigmoideum. After this procedure the mesenterial pedicle is fixed and the risk of midgut torsion remains minimal. All reported cases after surgery are symptom-free. PMID- 1857953 TI - Clot spotter. Does a test for fibrinogen predict risk of heart disease? PMID- 1857954 TI - Selling cells. Is a kidney cancer treatment a therapy or an experiment? PMID- 1857955 TI - Streptococcal M protein. PMID- 1857956 TI - Laser surgery. PMID- 1857957 TI - Polycyclic aromatic hydrocarbon (PAH) concentrations in ambient airborne particles from local traffic and distant sources; variation of the PAH profile. AB - The temporal and spatial dependence of the PAH profile, i.e. the relative concentrations of polycyclic aromatic hydrocarbons, was investigated for ambient airborne particles during a period with moderate photochemical air pollution. The concentrations of 14 PAH were measured; they differed in volatility, sensitivity to atmospheric chemical conversion and contributing sources. Multivariate analysis (principal-component analysis and factor analysis) revealed that temporal dependence was predominantly determined by five factors clearly linked with volatility, reactivity and sources of the PAH, the first being by far the most important. The results, therefore, indicate that volatilization, conversion and a varying contribution of local sources were the major causes of the variation of the profile with time. The contribution of local sources was investigated by comparison of samples that were taken simultaneously at three different sites, one a background site and two sites downwind of traffic. A marked site dependence was found. The comparison suggested that the differences were not only determined by sources, but also by volatilization and/or conversion during residence of the particles in the air. PMID- 1857958 TI - Benzene pollution from gasoline usage. AB - Local gasolines contain benzene ranging from 1.8 to 3.7% and their use can lead to significant exposure to benzene. Gasoline station attendants were found to be exposed to short-term exposure levels (STEL) of 0.064-179 ppm. Their 8-h time weighted averaged (TWA) exposure ranged from 0.028 to 0.71 ppm. For motorcar service mechanics, TWA exposure levels ranged from 0.014 to 1.7 ppm. The exposure of drivers of gasoline delivery tankers ranged from 0.08 to 2.37 ppm for personal TWA exposure over the whole workshift. For local people not occupationally exposed to gasoline or other benzene-containing volatile chemicals, exposure from the ambient environment ranged from 0.0023 to 0.027 ppm. Gasoline usage also contributed to the contamination of surface water with benzene. Benzene levels in water samples taken from drains leading from gasoline stations were between 1.1 and 40.4 micrograms l-1. PMID- 1857959 TI - Reproductive cycle and heavy metals in the organs of red mullet, Mullus barbatus (L.), from the northwestern Mediterranean. AB - Concentrations of the heavy metals Cd, Cu, Fe Mn, V and Zn have been measured in the principal tissues of the red mullet, Mullus barbatus (L.), during a complete sexual cycle. By comparison of metal levels during the reproductive and non reproductive periods, it was found that concentrations as well as total amounts of Cu, Mn and Zn in liver and gonads of male and female mullets were dependent upon the stage of the sexual cycle. No relationship with the sexual cycle was noted for these metals measured in muscle, kidney, spleen or pyloric caecum. Because of the observed variation in liver and gonad metal concentrations, these tissues appear to be poor indicators of ambient levels of metals in the surrounding waters. However, muscle may prove useful as an indicator tissue owing to its apparent independence of effects of the sexual cycle. PMID- 1857960 TI - The radioecological consequences for lowland pastures used to fatten upland sheep contaminated with radiocaesium. AB - Current farming practice in upland areas of Cumbria, England, affected by Chernobyl fallout is to remove lambs to lowland pastures for fattening prior to slaughter. The radiocaesium (137Cs and 134Cs) burden of lambs is rapidly lost via excreta deposited on the pasture. This may increase the radiocaesium activities in vegetation of these pastures. Studies were performed to assess the radioecological consequences of this practice. Results obtained from experiments were used to calibrate a soil/vegetation model which was used to predict long term radiocaesium behavior. PMID- 1857961 TI - Does war on cancer equal war on poverty? PMID- 1857962 TI - Promising AIDS drug looking for a sponsor. PMID- 1857963 TI - Oxygen activation at the diiron center of ribonucleotide reductase. PMID- 1857964 TI - Computations underlying the execution of movement: a biological perspective. AB - To execute voluntary movements, the central nervous system must transform the neural representation of the direction, amplitude, and velocity of the limb, represented by the activity of cortical and subcortical neurons, into signals that activate the muscles that move the limb. This task is equivalent to solving an "ill-posed" computational problem because the number of degrees of freedom of the musculoskeletal apparatus is much larger than that specified in the plan of action. Some of the mechanisms and circuitry underlying the transformation of motor plans into motor commands are described. A central feature of this transformation is a coarse map of limb postures in the premotor areas of the spinal cord. Vectorial combination of motor outputs among different areas of the spinal map may produce a large repertoire of motor behaviors. PMID- 1857965 TI - A mechanical trigger for the trot-gallop transition in horses. AB - It is widely thought that animals switch gaits at speeds that minimize energetic cost. Horses naturally switched from a trot to a gallop at a speed where galloping required more energy than trotting, and thus, the gait transition actually increased the energetic cost of running. However, by galloping at this speed, the peak forces on the muscles, tendons, and bones, and presumably the chance of injury, are reduced. When the horses carried weights, they switched from a trot to a gallop at a lower speed but at the same critical level of force. These findings suggest that the trot-gallop transition is triggered when musculoskeletal forces reach a critical level. PMID- 1857966 TI - Transcription-dependent and transcription-independent nuclear transport of hnRNP proteins. AB - Heterogeneous nuclear RNAs and specific nuclear proteins form heterogeneous nuclear ribonucleoprotein complexes (hnRNPs), one of the most abundant components of the nucleus. In mitosis, as the nuclear envelope breaks down, hnRNPs disperse throughout the cell. At the end of mitosis, hnRNPs dissociate and their proteins are transported into the daughter cell nuclei separately. Some are transported immediately (early group), while others are transported later (late group). Transport of the late group appears to require transcription by RNA polymerase II, in that inhibitors of this polymerase cause the late proteins to remain in the cytoplasm. Thus, there are two modes, transcription-dependent and transcription-independent, for the transport of nuclear proteins. PMID- 1857967 TI - Kinetic characterization of ribonuclease-resistant 2'-modified hammerhead ribozymes. AB - The incorporation of 2'-fluoro- and 2'-aminonucleotides into a hammerhead ribozyme was accomplished by automated chemical synthesis. The presence of 2' fluorouridines, 2'-fluorocytidines, or 2'-aminouridines did not appreciably decrease catalytic efficiency. Incorporation of 2'-aminocytidines decreased ribozyme activity approximately by a factor of 20. The replacement of all adenosines with 2'-fluoroadenosines abolished catalysis in the presence of MgCl2 within the limits of detection, but some activity was retained in the presence of MnCl2. This effect on catalysis was localized to a specific group of adenines within the conserved single-stranded region of the ribozyme. The decrease in catalytic efficiency was caused by a decrease in the rate constant; the Michaelis constant was unaltered. The 2'-fluoro and 2'-amino modifications conferred resistance toward ribonuclease degradation. Ribozymes containing 2'-fluoro- or 2' aminonucleotides at all uridine and cytidine positions were stabilized against degradation in rabbit serum by a factor of at least 10(3) compared to unmodified ribozyme. PMID- 1857968 TI - Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides. AB - Mycosis fungoides, a rare form of cutaneous T cell leukemia/lymphoma, is suspected of having a viral etiology on the basis of certain similarities to adult T cell leukemia, which is associated with human T cell leukemia/lymphoma virus type I (HTLV-I) infection. Cell lines were established from peripheral blood mononuclear cells (PBMC) of an HTLV-I-seronegative patient with mycosis fungoides. DNA hybridization analysis revealed the presence of HTLV-I-related sequences with unusual restriction endonuclease sites. Sequence analysis of subcloned fragments demonstrated the presence of a monoclonally integrated provirus with a 5.5-kilobase deletion involving large regions of gag and env and all of pol. Additional evidence for the presence of deleted proviruses was found by polymerase chain reaction (PCR) amplification of DNA from cutaneous lesions of five other HTLV-I-seronegative patients. The findings suggest that HTLV-I infection may be involved in the etiology of at least certain cases of mycosis fungoides. PMID- 1857969 TI - Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide. AB - Although the CD4 molecule is the principal cellular receptor for the human immunodeficiency virus (HIV), several CD4-negative cell lines are susceptible to infection with one or more HIV strains. These findings indicate that there are alternate modes of viral entry, perhaps involving one or more receptor molecules. Antibodies against galactosyl ceramide (galactocerebroside, or GalC) inhibited viral internalization and infection in two CD4-negative cell lines derived from the nervous system: U373-MG and SK-N-MC. Furthermore, recombinant HIV surface glycoprotein gp120 bound to GalC but not to other glycolipids. These results suggest a role for GalC or a highly related molecule in HIV entry into neural cells. PMID- 1857970 TI - Deposits of amyloid beta protein in the central nervous system of transgenic mice. AB - Alzheimer's disease is characterized by widespread deposition of amyloid in the central nervous system. The 4-kilodalton amyloid beta protein is derived from a larger amyloid precursor protein and forms amyloid deposits in the brain by an unknown pathological mechanism. Except for aged nonhuman primates, there is no animal model for Alzheimer's disease. Transgenic mice expressing amyloid beta protein in the brain could provide such a model. To investigate this possibility, the 4-kilodalton human amyloid beta protein was expressed under the control of the promoter of the human amyloid precursor protein in two lines of transgenic mice. Amyloid beta protein accumulated in the dendrites of some but not all hippocampal neurons in 1-year-old transgenic mice. Aggregates of the amyloid beta protein formed amyloid-like fibrils that are similar in appearance to those in the brains of patients with Alzheimer's disease. PMID- 1857971 TI - Evidence for the effects of a superantigen in rheumatoid arthritis. AB - While studying the alpha beta T cell receptor repertoire in rheumatoid arthritis (RA) patients, we found that the frequency of V beta 14+ T cells was significantly higher in the synovial fluid of affected joints than in the peripheral blood. In fact, V beta 14+ T cells were virtually undetectable in the peripheral blood of a majority of these RA patients. beta-chain sequences indicated that one or a few clones dominated the V beta 14+ population in the synovial fluid of individual RA patients, whereas oligoclonality was less marked for other V beta's and for V beta 14 in other types of inflammatory arthritis. These results implicate V beta 14-bearing T cells in the pathology of RA. They also suggest that the etiology of RA may involve initial activation of V beta 14+ T cells by a V beta 14-specific superantigen with subsequent recruitment of a few activated autoreactive v beta 14+ T cell clones to the joints while the majority of other V beta 14+ T cells disappear. PMID- 1857972 TI - The foreign policy of U.S. universities. PMID- 1857973 TI - Faculty retirement. AB - I would like to point out several errors of citation at the end of my article ;;Cocaine addiction: Psychology and neuropsychology'' (29 Mar., p. 1580). In the References and Notes, reference 42 was missing. It should have read, ;;42. T. Kosten et al., in preparation.'' Also in the References and Notes, reference 44 should have been numbered 43. In the text, citation 43 should have been numbered 41. In figure 3, the attribution was missing. It should have read, ;;Reprinted with permission from T. Kosten et al. (42).'' PMID- 1857974 TI - Artificial heart: the beat goes on. PMID- 1857975 TI - Sullivan overrules NIH on sex survey. PMID- 1857976 TI - Chiron buys Cetus: a tale of two companies. PMID- 1857977 TI - Kennedy resigns from Stanford. PMID- 1857978 TI - Computer tools for thinking in tandem. PMID- 1857979 TI - Networks for thinking in cliques? PMID- 1857980 TI - Panel wavers on roots of cancer. PMID- 1857981 TI - Making sense of antisense. PMID- 1857982 TI - A feast of gene-splicing down on the fish farm. PMID- 1857983 TI - Rules of language. AB - Language and cognition have been explained as the products of a homogeneous associative memory structure or alternatively, of a set of genetically determined computational modules in which rules manipulate symbolic representations. Intensive study of one phenomenon of English grammar and how it is processed and acquired suggest that both theories are partly right. Regular verbs (walk-walked) are computed by a suffixation rule in a neural system for grammatical processing; irregular verbs (run-ran) are retrieved from an associative memory. PMID- 1857984 TI - A component of calcium-activated potassium channels encoded by the Drosophila slo locus. AB - Calcium-activated potassium channels mediate many biologically important functions in electrically excitable cells. Despite recent progress in the molecular analysis of voltage-activated K+ channels, Ca(2+)-activated K+ channels have not been similarly characterized. The Drosophila slowpoke (slo) locus, mutations of which specifically abolish a Ca(2+)-activated K+ current in muscles and neurons, provides an opportunity for molecular characterization of these channels. Genomic and complementary DNA clones from the slo locus were isolated and sequenced. The polypeptide predicted by slo is similar to voltage-activated K+ channel polypeptides in discrete domains known to be essential for function. Thus, these results indicate that slo encodes a structural component of Ca(2+) activated K+ channels. PMID- 1857985 TI - Identification of profilin as a novel pollen allergen; IgE autoreactivity in sensitized individuals. AB - A complementary DNA encoding a pollen allergen from white birch (Betula verrucosa) that was isolated from a pollen complementary DNA library with serum immunoglobulin E from a birch pollen-allergic individual revealed significant sequence homology to profilins. The recombinant protein showed high affinity to poly-L-proline. Immunoglobulin E antibodies from allergic individuals bound to natural and recombinant birch profilin and also to human profilin. In addition, birch and human profilin induced histamine release from blood basophils of profilin-allergic individuals, but not of individuals sensitized to other plant allergens. The structural similarity of conserved proteins might therefore be responsible for maintaining immunoglobulin E antibody titers in type I allergy. PMID- 1857986 TI - Protein kinase activity closely associated with a reconstituted calcium-activated potassium channel. AB - Modulation of the activity of potassium and other ion channels is an essential feature of nervous system function. The open probability of a large conductance Ca(2+)-activated K+ channel from rat brain, incorporated into planar lipid bilayers, is increased by the addition of adenosine triphosphate (ATP) to the cytoplasmic side of the channel. This modulation takes place without the addition of protein kinase, requires Mg2+, and is mimicked by an ATP analog that serves as a substrate for protein kinases but not by a nonhydrolyzable ATP analog. Addition of protein phosphatase 1 reverses the modulation by MgATP. Thus, there may be an endogenous protein kinase activity firmly associated with this K+ channel. Some ion channels may exist in a complex that contains regulatory protein kinases and phosphatases. PMID- 1857987 TI - Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides. AB - To determine the role of the BCR-ABL gene in the proliferation of blast cells of patients with chronic myelogenous leukemia, leukemia blast cells were exposed to synthetic 18-mer oligodeoxynucleotides complementary to two identified BCR-ABL junctions. Leukemia colony formation was suppressed, whereas granulocyte macrophage colony formation from normal marrow progenitors was unaffected. When equal proportions of normal marrow progenitors and blast cells were mixed, exposed to the oligodeoxynucleotides, and assayed for residual colony formation, the majority of residual cells were normal. These findings demonstrate the requirement for a functional BCR-ABL gene in maintaining the leukemic phenotype and the feasibility of gene-targeted selective killing of neoplastic cells. PMID- 1857988 TI - Differentiation of 3T3-L1 fibroblasts to adipocytes induced by transfection of ras oncogenes. AB - Mammalian 3T3-L1 cells differentiate into adipocytes after continuous exposure to pharmacological doses of insulin or physiological doses of insulin-like growth factor I (IGF-1). Expression of transfected ras oncogenes led to differentiation of these cells into adipocytes in the absence of externally added insulin or IGF I. Cells transfected with normal ras genes or the tyrosine kinase trk oncogene did not differentiate. Transfection with a dominant inhibitory ras mutant resulted in inhibition of differentiation. Exposure of untransfected 3T3-L1 cells to insulin stimulated formation of the active Ras.GTP complex. These observations indicate that Ras proteins participate in signal transduction pathways initiated by insulin and IGF-I in these cells. PMID- 1857989 TI - [Assessment of quality of life in rheumatoid arthritis]. PMID- 1857990 TI - [Clinical evaluation of the effects of CN-100 on osteoarthritis deformans of the knee]. PMID- 1857991 TI - [A clinical evaluation of CN-100 in patients with rheumatoid arthritis]. PMID- 1857992 TI - [Evaluation of two quantitative tests for salivary secretion--the chewing gum test and the Saxon test in normal subjects and in patients with Sjogren's syndrome]. AB - A cooperative multicenter study was performed to evaluate two salivary secretion methods-the chewing gum test and the Saxon test by a crossover method. Twenty healthy volunteers and 27 patients with Sjogren's syndrome were examined. In healthy controls the amount of saliva collected per minute was larger in the Saxon test. Both tests revealed a significant decrease of salivary secretion in patients with Sjogren's syndrome, but the amount of saliva per minute was also larger in Saxon test. By repeated trials of both tests a notable increase of saliva was always observed at the second trial. Since this phenomenon may be due to the learning effect of the tests, one should perform at least one practice before starting formal tests. Saxon test could be performed in a patient having dental prostheses who was unable to masticate chewing gum. The Saxon test, thus, may be an efficient method, to evaluate the salivary secretory function. PMID- 1857994 TI - [Analysis of components of immune complexes in sera of patients with systemic lupus erythematosus]. AB - The samples of immune complexes (IC) isolated through Clq tube from serum of SLE patients were analysed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting for their antigens and antibodies. The isolated IC contained gamma, mu and L chain of immunoglobulin and various sizes of DNA ranging from 16KD to 55KD. The isolated IC showed antibodies reacting to 16KD DNA. In the isolated IC, DNAs with molecules less than 300 base pairs were detected. These DNA were double-stranded and hybridized with nuclear DNAs originated from human but not from other species. PMID- 1857993 TI - [A study on treatment of hyperuricemia--effects and kinetics of allopurinol and oxipurinol]. AB - In order to study the effects and pharmacokinetics of allopurinol (hereafter abbreviated to allo.) and oxipurinol (hereafter abbreviated to oxi.) six normal human subjects were given a single oral dose of either allo. (300mg) or oxi. (600mg), followed by serial determinations of serum and urinary levels of allo., oxi., uric acid, hypoxanthine (hereafter abbreviated to hx.) and xanthine (hereafter abbreviated x.) over a six-hour period. With a dose of 300mg of allo. or 600mg of oxi., the patterns of serum uric acid were similar. When 300mg of allo. was given, however, a reduction in the serum uric acid level occurred earlier. Additionally, it was found that urinary excretion of oxi. generally paralleled the plasma concentration. Allo. administration resulted in rises in plasma concentration of x., and urinary excretion of x. and hx. Oxi. administration, on the other hand, did not cause significant changes in the plasma content of x. or urinary excretory volume of hx. Only a slight increase was noted in the amount of x. excreted in the urine. When allo. was compared against oxi., pharmacokinetics of oxypurines, especially x. were found to differ markedly. The results suggested that differences in the reaction sites, varied intra- and extra-cellular distributions of allo. and oxi., and different effects on purine biosynthesis contribute to the aforementioned discrepancies. PMID- 1857995 TI - [Change of joint synovial clearance speed in experimental arthritis]. AB - The radio activity of 131I-Hippuran injected into the knees was investigated in rabbits and found to decrease with passage of the time. The disappearance curve was monoexponential and the disappearance rate was able to be obtained by a biological half life (T 1/2). This evidence showed that 131I-Hippuran was absorbed from the knee and excreted into body blood circulation but was not able to return to the knee again, and might provide a suitable parameter for the joint clearance. The mean value of T 1/2 in normal 25 knees was 13.9 +/- 4.5 min. The effect of 0.1N oxalic acid on the T 1/2 was investigated in 20 knees 24 hours after intra-articular injection, in 17 knees 4 days, in 14 knees 7 days, in 11 knees 12 days and in 9 knees 20 days. The mean T 1/2 value was 50.4 +/- 9.8 min., 30.6 +/- 6.2 min., 20.9 +/- 4.4 min., 15.2 +/- 2.2 min., and 13.7 +/- 2.5 min., respectively. The significant difference was observed between the groups of 24 hours, 4 days and 7 days. Hemorrhagic arthritis was observed in the rabbit knee with oxalic acid injection. The very severe hemorrhagic change was observed in the specimen obtained 24 hours and 4 days after the injection. On the 7 days after that the arthritic condition began to heal and almost complete healing was observed on 12 to 20 days. These results indicated that the joint clearance of 131I-Hippuran was reflected well in the pathological change induced by oxalic acid. It is interpreted to mean that the inhibition of synovial blood circulation by oxalic acid might cause decrease of absorption and clearance rate of 131I Hippuran in the knee. It is thought that the measurement of the biological half life (T 1/2) after the intra-articular injection of 131I-Hippuran is a suitable method mainly to understand the condition of absorption and excretion of the joint through the synovial blood vessels. PMID- 1857996 TI - [A case of primary Sjogren's syndrome presenting as osteomalacia secondary to renal tubular acidosis]. AB - We report a 43-year-old female with primary Sjogren's syndrome (SjS) who presented as osteomalacia due to distal renal tubular acidosis (RTA). Osteomalacia was thought to be a rare complication of RTA in SjS, although it had been often described in association with RTA in general. In 1979, she presented with dry mouth, parotid gland swelling and leg purpura. A diagnosis of primary SjS and hyperglobulinemic purpura was made on the basis of positive staining with Rose Bengal stain, sialography of the parotid gland and histological examination of the salivary gland of the lip. She was admitted to Jichi Medical School Hospital in March 1988 with chest pain. X-ray films revealed pseudofractures of bilateral ribs. Bone scanning showed abnormal multiple accumulation of RI on the same parts. Laboratory studies on admission revealed: GOT 50 IU/ml, GPT 9 IU/ml, ALP 190 IU/ml, LDH 301 IU/ml, BUN 11.0 mg/dl, creatinine 1.0 mg/dl, uric acid 2.7 mg/dl, total protein 7.4 g/dl (gamma globulin 22.3%), sodium 141 mEq/l, potassium 3.7 mEq/l, chloride 106 mEq/l, calcium 8.9 mg/dl, and phosphorus 2.4 mg/dl. Arterial blood gas studies on room air showed: PO2 96.7mmHg, PCO2 35.5mmHg, HCO3 19.1 mEq/l, PH 7.347 and base excess -5.4 mEq/l. The urinalysis showed: specific gravity 1.008, PH 7.0, and no protein and glucose. Immunologically, antinuclear antibody was positive at 1:640 with a speckled pattern. Anti-DNA antibody was negative. Antibodies to SS.A and SS.B were 1:64 and 1:32 respectively. Distal RTA was confirmed by the sodium bicarbonate and NH4Cl loading test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1857997 TI - [A case of rheumatoid arthritis complicated with auranofin-induced acute interstitial pneumonitis]. AB - A case of auranofin(AF)-induced acute interstitial pneumonitis in a patient with rheumatoid arthritis (RA) is reported and possible mechanism of the incidence is discussed. A 57 year-old woman with a history of RA starting in early April 1989, had been prescribed AF for seven days prior to her referral to this hospital. Because of the severity of her polyarthritis, AF was discontinued; therapy with gold sodium thiomalate (GST) instead was started on 23 June 1989. The patient responded quite favorably. At a total cumulative dose of 160mg of GST, however, she developed generalized exfoliative dermatitis and the drug was discontinued. On 29 Sept. 1989 when her skin lesions cleared up completely, she was put on AF again. Six days after resumption of AF therapy, she developed fever. Nonproductive cough and dyspnea on exertion was observed within the following three days. The chest X-ray film revealed diffuse reticular-linear infiltrates more prominently in both upper lobes. Arterial blood gas studies showed hypoxemia and a restrictive ventilatory defect was demonstrated by pulmonary function studies. AF was stopped. High dose pulse iv corticosteroid(CS) therapy combined with oral CS was instituted. Immediate improvement of both subjective and objective findings was observed. By using the patient's peripheral blood lymphocytes, delayed lymphocyte stimulation test(DLST) against the probable causative agents was performed before the bolus CS therapy. Stimulation Index(shown in percentage) was markedly elevated in AF(724%) as compared with GST(163%). The fiberoptic bronchoscopy with bronchoalveolar lavage(BAL) was performed. Analysis of BAL fluid revealed increased cellularity (9 x 10(5)/ml) with marked lymphocytosis of 79%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1857999 TI - [Receptors in rheumatoid arthritis]. PMID- 1857998 TI - [Histopathological examination of a case of Behcet's disease with aortic regurgitation]. AB - Cardiac involvement in Behcet's disease is quite uncommon. We report a case of Behcet's disease with aortic regurgitation of which histology was examined. A 56 year-old male came to our hospital with a complaint of right cervical pain. Diagnosis of aortic regurgitation was made by echocardiography, cardiac catheterization and aortography. As the cardiac lesion worsened, the operation of the aortic valve replacement was performed. On pathological examination, there was marked fibrous thickening on the aortic valve and the rupture of elastic tissue in the media of aortic wall. There was no history of rheumatic fever nor syphilis, and dilation of orifice of the aorta was not observed. Thus these changes were probably due to Behcet's disease itself. PMID- 1858000 TI - [Epidemiology study on upper gastrointestinal lesions induced by non-steroidal anti-inflammatory drugs]. PMID- 1858001 TI - Medicare costs prior to retirement for disabled-worker beneficiaries. PMID- 1858002 TI - Public social welfare expenditures, fiscal year 1988. PMID- 1858003 TI - Hereditary colon cancer syndromes. PMID- 1858004 TI - Chronic gastritis. PMID- 1858005 TI - The use of endothelial seeding of prosthetic arterial bypass grafts. AB - Endothelial seeding is the transplantation of vascular lining cells. On the basis of animal studies and theoretical considerations, seeding is expected to reduce acute thrombosis and stenoses because of NFH when segments of the vascular system are denuded of endothelium. Endothelialization may reduce the susceptibility of synthetic grafts to blood-borne bacterial infection. Seeding demonstrably transfers endothelium in humans. The indications for its use are limited to clinical trials in aorta-femoral and femoral-popliteal bypass operations, and the results of those trials will begin to define its indications further. In the future, endothelium may be applied to tibial and coronary synthetic arterial grafts; sites of endarterectomy, PTA, atherectomy, and laser treatments; vascular access; and venous replacement grafts. PMID- 1858006 TI - Intestinal ischemia. PMID- 1858007 TI - New concepts in experimental peptic ulceration. PMID- 1858008 TI - Update on the status of fetal surgery. PMID- 1858009 TI - Current concepts in the management of urethral strictures. PMID- 1858010 TI - Application of laser energy in urologic surgery. PMID- 1858011 TI - Fecal diversion for Crohn disease of the colon. PMID- 1858012 TI - [The value of and indications for radiotherapy in endometrial carcinoma]. AB - Today the endometrial carcinoma is the most frequent malignant tumor found in female genital tract. Endometrial carcinoma ought to be operated in all cases, if possible. Traditionally some form of adjuvant radiotherapy has been given. Despite the large number of patients treated by combined therapy over the last 30 years, surprisingly there is a lack of hard data on which to establish a theory for an improved outcome. It is generally accepted that the risk of local relapses in the vagina is lowered when postoperative vaginal irradiation is applied. The question of the value of additional external irradiation in stage I endometrial cancer still is unsettled. Only two prospective studies led to the conclusion that only patients with poorly differentiated tumors and with deep infiltration of the myometrium might benefit from additional external radiotherapy. Therefore a simple score for these risk factors is proposed enabling assignment into patient groups of similar risk on the base of a point system due to individual prognostic factors. With a score of one to two points prognosis is very good and adjuvant irradiation seems not to be necessary. With three to four points local vaginal irradiation is recommended, with five and more points additionally external beam irradiation to the pelvis should be given. This is necessary in more than the half of the operated cases of endometrial carcinoma. The indication for such a treatment has become more individual and "high risk" cases are treated more intensively, but "low risk" cases have to be excepted from unnecessary adjuvant therapy. In order to judge an individual case of endometrial cancer histopathologic prognosticators have to be considered. Typical adenocarcinomas have a five-year survival of more than 80%, but unfavourable subtypes (adenosquamous, clear-cell, serous-papillary carcinomas) of only 40%, respectively. Tumor grading and depth of myometrial invasion are of high importance for individual prognosis. The new histopathologic staging system of FIGO (1988) takes these items into account. Only patients with severe internal diseases should be treated with radiation therapy alone. Although radiation therapy alone can cure endometrial cancer (five-year-survival approximately 60%), the survival figures are poorer than for the operation (five-year survival 80%, respectively). It should be outlined that in inoperable cases radiotherapy is the best form of treatment. PMID- 1858013 TI - Radiotherapy of primary human melanomas--experiences and suggestions. AB - We treated 60 invasive primary human melanomas by soft X-rays. In 23 additional cases radiotherapy was applied after total excision of a primary melanoma. Only in two cases was a tumor observed in the field of irradiation during the follow up period: a recurrence of a primary melanoma and a skin metastasis. Radioresistance cannot be unequivocally assumed in either case. Since deeply situated in-transit metastases cannot be destroyed by soft X-rays in spite of our good results we regard radiotherapy of invasive primary melanomas as a second choice treatment to be administered if impaired general health, excessive tumor growth in certain localisations or refusal of the patient do not allow a major operation. Nodular parts of primary melanomas should be excised before radiotherapy to obtain material for histopathological confirmation of the diagnosis and to determine the thickness of the tumor. X-rays of lower hardness can subsequently be applied. PMID- 1858014 TI - Total-skin electron irradiation for cutaneous T-cell lymphoma: the Northern Israel Oncology Center experience. AB - Total-skin electron irradiation (TSEI) is effective and frequently used in the treatment of cutaneous T-cell lymphoma. A treatment technique has been developed at our center, using the Philips SL 75/10 linear accelerator. In our method, the patient is irradiated in a recumbent position by five pairs of uncollimated electron beams at a source to skin distance of 150 cm. This method provides a practical solution to clinical requirements with respect to uniformity of electron dose and low X-ray contamination. Its implementation does not require special equipment or modification of the linear accelerator, 19 of 23 patients (83%) with mycosis fungoides, treated by this method, achieved complete regression of their cutaneous lesions. PMID- 1858015 TI - Treatment of keloids by 90Sr-90Y beta-rays. AB - The use of radiations for the treatment of keloids was the topic of debate for years. Because of the benign nature of the keloids, surgery (keloidectomy) was treatment of choice. However, the use of surgery alone for arresting the keloids growth does not give satisfactory results due to the high frequency of recurrences. In this study 110 symptomatic cases were treated with 90Sr-90Y beta radiation either alone for flat keloids or in combination with surgery for thick keloids. The results obtained with this method were found to be quite satisfactory. Patients were given four fractions of 5 Gy per fraction either as weekly or twice weekly schedules. Radiation dose of 2000 cGy given twice weekly in four fractions showed response in 86% of the cases as compared to 73% in those receiving four fractions of 5 Gy weekly. Further observations on different time dose fractionation schedules would open up newer dimensions in the radiotherapy of keloids. PMID- 1858017 TI - [In vivo dosimetry in interstitial "low dose rate" afterloading therapy with Ir 192 seeds exemplified with head-neck tumors]. AB - An in vivo measuring method is introduced from mending the calculated lying time of implants corresponding to the given dose (reference dose) in the interstitial brachytherapy with iridium-192 seeds. The small effort for using this method and the relatively easy way of handling it allow its clinical use for quality assurance in brachytherapy. PMID- 1858016 TI - [Radiotherapy of solitary and multiple eosinophilic granulomas of bone (stage I)]. AB - Between 1957 and 1990 15 patients with solitary (stage Ia by Greenberger) and 2 patients with multiple (stage Ib) eosinophilic granuloma of the bone were treated by radiotherapy in 18 locations after previous surgery. The doses applied varied from 6 Gy to 42 Gy (median for patients under 18 years: 8 Gy, for patients over 18 years: 30 Gy). Median follow-up was 9 years (range, 0.3-33 years). Local control rate and survival were 100%. Three patients with granuloma developed a second granuloma within 13 years after primary diagnosis (two bone manifestations, one cutaneous manifestation). Long-term follow-up of patients with solitary eosinophilic granuloma is necessary. PMID- 1858018 TI - [Quality assurance in x-ray installations for therapy in accordance with the x ray regulations]. AB - For the conventional X-ray therapy the Rontgenverordnung demands the examination of the dose rate in the radiation beam. The measurements and the results are demonstrated. Over a long period the X-ray equipment shows a constant dose rate. Controls of the technical devices and situations of danger are explained. PMID- 1858019 TI - [Mounting devices for screening blocks on the linear accelerator--the drawbacks and modifications]. AB - Block mounting devices for linacs--drawbacks and modifications: Shielding blocks are often used in radiotherapy. They are fixed on the linac's head by means of standard accessory mounting devices. The disadvantages of these parts are discussed and two modifications are presented: One device with adjustable focus support distance for standard lead blocks and another with gliding planes to insert easily the heavy individually formed shielding blocks. Errors in mounting of all these devices are very dangerous, so we developed a simple locking lever providing a high security. PMID- 1858020 TI - Antiradiation mixture and ionic-bond product of AET and adenyl nucleotides. AB - These experiments continued our line of inquiry into low-toxicity high effectiveness radiomodifying agents obtained by binding radioprotective substances to biogenic and biologically active components or antidotes. Testes for toxicity and radioprotective effects were three preparations combining within one molecule AET and an adenyl nucleotide (AMP, ADP, or ATP). Ionic-bond formation was shown to have advantages over concomitant administration of AET and adenosine phosphoric acids as mixtures. The evidence obtained supports the rational foundation of the concept being developed by our laboratory. PMID- 1858021 TI - Biophysical aspects of the integrated combination of cytostatic drugs with radiotherapy. Part 1: In vitro investigations on the kinetics of activated isophosphamide metabolites and the determination of selective properties of DNA interstrand and DNA-protein crosslinking mechanisms using 31P-NMR spectroscopy. AB - The pH dependence of the kinetics of the "activated" isophosphamide metabolites 4 hydroxy-isophosphamide, isoaldophosphamide and isophosphoramide mustard has been characterized with the help of 31P-NMR Fourier spectroscopy. The most outstanding feature is the pH-dependence of the decay kinetics of 4-hydroxy-isophosphamide and isoaldophosphamide yielding the alkylating moiety isophosphoramide mustard and acrolein. With the same spectroscopic technique the alkylation of biomolecules containing guanine (cGMP, GDP, GTP, synthetic oligodeoxynucleic acid serving as a surrogate of DNA) and proteins containing cysteine as receptor molecule have been analyzed. The kinetic data provide information on combining the measured substrates with radiotherapy to be presented in further communications. PMID- 1858022 TI - [A commentary on M.L. Sautter-Bihl et al.: The radiotherapy of glioblastoma--is a dosage reduction justifiable?]. PMID- 1858023 TI - In defense of information or defenders of the faith. PMID- 1858024 TI - Endothelium-dependent contraction and relaxation of the human and canine internal mammary artery: studies on bypass graft vasospasm. AB - The internal mammary artery (IMA) is the preferred conduit for coronary artery bypass graft because of superior late patency. However, IMA vasospasm may contribute to myocardial ischemia and early postoperative morbidity. To investigate mechanisms of vasospasm, we compared the reactivity of human and canine IMA segments in vitro to agonists known to release endothelium-derived contracting factor and endothelium-derived relaxing factor. Rings (4 mm in length) of human and canine IMA were studied in organ chambers. Human and canine vascular smooth muscle exhibited comparable contraction to norepinephrine (maximum = 7.55 +/- 0.63 gm and 6.4 +/- 0.90 gm, respectively) and relaxation to sodium nitroprusside. Human and canine IMAs exhibited comparable endothelium derived relaxing factor-mediated relaxations to acetylcholine (human) and methacholine (canine). Human and canine IMA also exhibited comparable endothelium dependent contraction to hypoxia (to 173.3% +/- 8.1% and 178.9% +/- 16.0% of initial prehypoxic tension; means +/- SEM; n = 12). Endothelium-dependent contraction to hypoxia in human and canine IMA could be attenuated by NG monomethyl-L-arginine (10(-6) mol/L), a competitive inhibitor of L-arginine metabolism (n = 9 and n = 10 for human and canine; p less than 0.05). These studies establish that the canine is an appropriate model for study of human IMA vascular reactivity and that hypoxia can induce the release of an L-arginine dependent, endothelium-derived contracting factor in the human and canine IMA. In vivo, the release of endothelium-derived contracting factor in response to hypoxemia may be cause of IMA vasospasm. PMID- 1858025 TI - Enhanced interstitial fluid adenosine attenuates myocardial stunning. AB - Reversible myocardial dysfunction associated with transient ischemia has been termed the stunned myocardium. Because exogenous adenosine has been shown to protect the ischemic myocardium, we hypothesized that augmentation of endogenous adenosine levels would attenuate myocardial stunning. To induce stunning, anesthetized dogs were subjected to 15 minutes of ischemia (left anterior descending artery occlusion) followed by 60 minutes of reperfusion. Erythro-9-(2 hydroxy-3-nonyl) adenine (EHNA; 5 mg/kg/hr), an adenosine deaminase inhibitor, was used to augment adenosine levels. The effect of EHNA on interstitial fluid (ISF) adenosine levels, coronary blood flow, and regional systolic wall thickening was compared with that of an untreated group (n = 8). EHNA increased preischemia ISF adenosine levels threefold and was associated with a corresponding increase in coronary blood flow. EHNA administration did not alter preischemia systolic wall thickening. Although ISF adenosine increased fourfold during ischemia in the untreated group, ISF adenosine increased nearly sixtyfold above preischemia values in the EHNA-treated group and remained elevated throughout reperfusion. Postischemic regional function was enhanced significantly in the group treated with EHNA. These data show that adenosine deaminase inhibition increased ISF adenosine levels and attenuated myocardial stunning. Metabolic manipulation of myocardial ISF nucleoside levels may be beneficial in limiting postischemic myocardial dysfunction. PMID- 1858026 TI - Effects of distention and short-term grafting on vasoreactivity in rabbit external jugular veins. AB - The relative effects of distention, intraluminal pressure, and wall tension on venous smooth muscle and endothelial cell function were examined in 40 external jugular veins from New Zealand white rabbits. Vein grafts (n = 5) were interposed in the common carotid artery and explanted after 10 minutes. Distended veins were inflated in vitro with modified Krebs' solution at 37 degrees C for 10 minutes at pressures of either 20 mm Hg (D-20; n = 5) or 80 mm Hg (D-80; n = 5). Externally supported veins (ES-80; n = 5) were inflated at 80 mm Hg pressure, but distention was prevented by covering with a 3 mm internal diameter polytetrafluoroethylene sleeve. Bradykinin-induced in vitro maximal tension was attenuated significantly in vein grafts (0.13 +/- 0.04 g) and D-80 rings (0.27 +/- 0.07 g) compared with D 20 rings (1.20 +/- 0.14 g), ES-80 rings (0.99 +/- 0.13 g), or nondistended control rings (n = 40; 1.19 +/- 0.10 g; p less than 0.001). The attenuation in contraction in the vein graft and D-80 groups was nonspecific (i.e., similar results were obtained with respect to other smooth muscle agonists). Contractile function was inversely associated with wall tension, the product of pressure and radius (r2 = 0.7438; p = 0.06). In contrast, there were no differences in endothelium-dependent or endothelium-independent relaxation among the five groups. It is concluded that, in this experimental system, (1) venous smooth muscle function is significantly attenuated after short-term in vitro distention or grafting although endothelial function is largely preserved, and (2) the decrement in contraction is due to elevated wall tension. PMID- 1858027 TI - Hepatic failure and coma after liver resection is reversed by manipulation of gut contents: the role of endotoxin. AB - Despite significant improvements in the surgical care of patients, hepatic failure after extensive liver resection continues to be associated with a high morbidity and death. We postulated that hepatic failure after liver resection was related to gut-derived endotoxemia. Rats were randomized to receive oral gavage twice daily with one of the following preparations: (1) 0.9% saline; (2) neomycin sulfate and cefazolin; (3) cholestyramine; (4) lactulose. After 7 days of gavage, animals underwent either a two-thirds partial hepatectomy or sham operation. At time 0 (preresection), 10, 20, and 30 hours after resection, aortic blood was obtained for determination of ammonia, glutamine, and endotoxin levels. In selected animals, portal vein or inferior caval blood was obtained simultaneously with the aortic sample to evaluate the glutamine and ammonia exchange across the intestine and hind limb. Germ-free rats also underwent a partial hepatectomy or sham operation, and blood was obtained for glutamine and ammonia exchange at 0 and 20 hours after resection. Hepatectomy in the saline-pretreated rats resulted in a sixfold increase in plasma glutamine, increased uptake of glutamine and release of ammonia by the gut, increased release of glutamine by the hind-limb, and a high mortality rate. Pretreatment with agents that altered gut contents reduced the endotoxemia, maintained normal glutamine and ammonia levels, and reduced the mortality rate. Germ-free rats had a similar response to that seen in treated animals. Altering the gut contents in this model reduced the level of endotoxemia, blunted the catabolic response, and enhanced survival. PMID- 1858028 TI - Cholestasis without cirrhosis alters regulatory liver gene expression and inhibits hepatic regeneration. AB - Partial hepatectomy (PH) initiates cellular signals for regeneration. Sequential expression of nuclear and cytosolic protooncogenes accompanies the restoration of normal liver function and architecture. Although cirrhosis is known to inhibit liver regeneration, the effects of noncirrhotic cholestasis on hepatocellular proliferation, differentiation, and regulatory gene expression are unknown. To examine this, 25 male Fisher rats underwent common bile duct ligation and division. A 47% +/- 5% PH was performed 10 days after common bile duct ligation and division when histologic analysis revealed cholestasis without cirrhosis. Despite early elevations of total hepatic DNA and RNA values, cholestatic livers demonstrated a significant threefold suppression of expected hepatocyte mitotic indexes 48 and 72 hours after PH, compared with livers after PH alone. Weight restoration in cholestatic livers was 11% +/- 5.2% compared with 40% +/- 4.3% in control livers (+/- SEM; p less than 0.001) 5 days after PH. Analysis of regenerating liver messenger RNA with complementary DNA probes revealed an abnormal, sustained elevation of K-ras expression in cholestatic livers through all time points. Cholestasis blunted but did not obliterate normal sequential elevations in H-ras found in control livers. The expression of c-myc was inhibited threefold with cholestasis 72 hours after PH. These results are the first indication that cholestasis alone inhibits hepatocyte proliferation and the expression of c-myc that normally precedes the first wave of mitosis. This implies that cholestasis without cirrhosis may alter programmed liver gene expression, inhibiting normal hepatic regeneration. PMID- 1858029 TI - Pentoxifylline suppression of tumor necrosis factor gene transcription. AB - Pentoxifylline decreases lung injury after intravenous endotoxin; the mechanism is unknown. Tumor necrosis factor-alpha (TNF) is secreted by macrophages in response to endotoxin and mediates some of the toxicity of endotoxin. This study investigates the effects of pentoxifylline on endotoxin-stimulated TNF production in vitro and in vivo. Pentoxifylline concentrations of 100 and 1000 micrograms/ml inhibited TNF production by murine adherent peritoneal exudate cells incubated with endotoxin 1 microgram/ml. Similarly, pentoxifylline at 100 and 1000 micrograms/ml decreased the number of available TNF messenger RNA transcripts in peritoneal exudate cells assessed by Northern blot. Pentoxifylline had no effect on TNF mRNA stability, but appeared to act by inhibiting the rate of TNF mRNA production (transcription). In murine in vivo experiments at each dose of endotoxin administered from 0.01 to 30 mg/kg, pentoxifylline treatment significantly reduced serum TNF levels, suggesting a favorable shift of the endotoxin dose-response curve. Expression of murine TNF gene in the livers of these animals showed fewer TNF transcripts in the pentoxifylline-treated animals compared to controls. Pentoxifylline inhibited endotoxin-induced TNF production both in vivo and in vitro and exerted this control by inhibiting endotoxin induced transcription of the TNF gene. This study suggests that pentoxifylline may ameliorate endotoxic shock by decreasing macrophage TNF production. PMID- 1858030 TI - Pentoxifylline inhibits interleukin-2-induced leukocyte-endothelial adherence and reduces systemic toxicity. AB - Interleukin-2 (IL-2) mediates the regression of metastatic cancer, but clinical application has been limited by the induction of dose-dependent toxicities in normal tissues. The most clinically significant toxicities occur secondary to a vascular leak syndrome and include acute respiratory failure and hemodynamic instability. Because previous studies suggested a role for pentoxifylline in attenuating the toxic effects of IL-2, we hypothesized that pentoxifylline would inhibit alterations in the microvasculature induced by IL-2 and would ultimately reduce IL-2-induced toxicity. To determine the validity of this hypothesis, we prepared four groups of rats for in vivo microvascular observation. In the first group, a bolus intravenous injection of IL-2 (1 x 10(6) units/kg) acutely induced hypotension, tachypnea, hypoxia, increased lung water, decreased microvascular blood flow, and increased leukocyte-endothelial adherence. No significant changes occurred in animals treated by pentoxifylline alone or the control IL-2 vehicle alone group. However, pentoxifylline inhibited many of the IL-2-induced systemic and microvascular effects, such as hypotension, tachypnea, increased lung water, hypoxia, and increased leukocyte-endothelial adherence, but not tachycardia or increased microvascular protein leakage. These data support our hypothesis that systemic toxicities induced by IL-2 are associated with alterations in the microcirculation, which may be ameliorated by pentoxifylline. PMID- 1858031 TI - A biologic basis for limited Kupffer cell reactivity to portal-derived endotoxin. AB - Despite continuous exposure to gut-derived endotoxin (lipopolysaccharide) under normal conditions, Kupffer cells (KC) fail to generate detrimental cytokine responses. KC function within a unique microenvironment in which high hepatic arginase activities (25 times greater than those activities in the kidney) result in negligible local L-arginine levels. To evaluate the relevance of this profound arginine deficiency on the physiologic function of KC, the kinetics of tumor necrosis factor (TNF-alpha) production and autoregulatory eicosanoid prostaglandin E2 (PGE2) production were compared in lipopolysaccharide-stimulated KC cultured with (1200 mumol/L) and without (10 mumol/L) L-arginine media. In (+)arginine culture the KC TNF-alpha production peaked early before decreasing as PGE2 production increased. In (-)arginine culture, however, KC TNF-alpha production was significantly (p less than 0.01) reduced, whereas PGE2 production was amplified (p less than 0.01). When cyclooxygenase blockade with indomethacin completely prevented KC production of PGE2 in (-)arginine culture, TNF-alpha production was upregulated (p less than 0.001 vs (-)arginine; p not significant vs (+)arginine). These arginine-specific depression of TNF-alpha responses appeared unique to KC because both TNF-alpha and PGE2 levels increased when peritoneal, pleural, and alveolar macrophages were stimulated by lipopolysaccharide in (-)arginine medium. This PGE2-dependent autoregulation of potentially harmful lipopolysaccharide-induced TNF-alpha responses may reflect an evolutionary adaptation by KC to their local hepatic environment and strategic anatomic position in the portal circuit, which optimally removes endotoxin and naturally protects the host. PMID- 1858032 TI - Chemotherapy amplifies production of tumor necrosis factor. AB - Several chemotherapeutic agents exert cytotoxicity through the generation of reactive oxygen species (ROS), and our laboratory has shown that ROS increase tumor necrosis factor (TNF) production. Therefore, we hypothesized that cis dichlorodiammine platinum (CDDP), mitomycin-C, and doxorubicin hydrochloride (Adriamycin), by the release of ROS, would increase macrophage TNF production. Murine macrophages were incubated for 20 hours with varying doses of the chemotherapeutic drugs and 2.5 micrograms/ml endotoxin. Both CDDP and mitomycin-C increased TNF production compared to nondrug-exposed cells. Peak TNF values occurred at 10 micrograms/ml CDDP and 62.5 micrograms/ml mitomycin-C with 377 +/- 38 and 427 +/- 54 units/ml TNF produced, respectively. These increases were significant (p2 less than 0.05) compared to the nonchemotherapy; but endotoxin exposed macrophages (CDDP 11 +/- 3 units/ml; mitomycin-C 10 +/- 3 units/ml). Only CDDP-increased production of TNF from non-endotoxin-primed macrophages (0 microgram/ml CDDP - 0 +/- 0 unit/ml TNF; 50 micrograms/ml CDDP - 13 +/- 5 units/ml TNF; p2 less than 0.038). 5-Fluorouracil, a non-ROS-generating chemotherapeutic, and Adriamycin failed to amplify TNF production. By Northern blot analysis, CDDP induced transcription of the TNF gene in non-endotoxin-primed macrophages as early as 3 hours after exposure to 50 micrograms/ml CDDP, and this preceded the increase in TNF protein in kinetic studies. Because CDDP, mitomycin C, and Adriamycin all produce ROS, the mechanism for this selective chemotherapy induced cytokine amplification remains unclear. This finding may explain both indirect toxic and tumoricidal properties of CDDP and mitomycin-C. PMID- 1858033 TI - Kinetics of early T-cell repopulation in fully xenogeneic chimeras (F344 rat--- B10 mouse): evidence for rat T-cell maturation in a xenogeneic mouse thymus. AB - We recently reported the model of fully xenogeneic chimerism achieved by transplantation of rat bone marrow into mouse recipients (F344 rat----B10 mouse), resulting in stable long-term rat lymphoid chimerism. We have now extended this model to examine whether developing precursor rat T cells from rat bone marrow stem cells can undergo normal differentiation in mature lymphocytes under the influence of a xenogeneic mouse thymus. We examined thymic and splenic lymphoid cells from fully xenogeneic chimeras starting 1 week after bone marrow transplantation to characterize early T-cell repopulation and phenotype. Our data suggest that developing rat precursor T cells are able to undergo normal differentiation in the mouse thymus. The first precursor T cells appeared 2 weeks after reconstitution and by week 10 accounted for more than 90% of thymocytes present in the chimeras. In chimeras, developing rat T lymphocytes in the mouse thymus exhibited an immature pattern (Thy 1.1+, alpha beta-TCRdull, CD4+ plus CD8+) when analyzed by flow cytometry. This pattern was similar to a normal rat. In contrast, splenic T-lymphoid cells showed a mature rat phenotype (Thy 1.1-, alpha beta-TCRhi, CD4+ or CD8+), again similar to a normal rat. This development began 2 weeks after bone marrow transplantation, and both thymus and spleen from chimeras exhibited "normal" rat T-cell staining profiles by 10 weeks after reconstitution. Overall, these data indicate that developing rat T cells are capable of undergoing normal maturation in a xenogeneic mouse thymus of tolerant animals. PMID- 1858034 TI - Posttranscriptional regulation of neurotensin in the gut. AB - Previous studies have suggested an important role for neurotensin as an enterotrophic factor in the adaptive response of the gut. The purpose of this study was to determine the specific tissue distribution of neurotensin messenger RNA (mRNA) and to examine the molecular mechanisms that regulate intestinal neurotensin gene expression and content. In the first experiment, various segments of gut tissue from three Sprague-Dawley rats were harvested, and polyadenylated RNA was extracted for Northern hybridization with a rat neurotensin probe. In the second experiment, 32 Sprague-Dawley rats were fasted for 72 hours and then killed at 0, 3, 12, and 24 hours after refeeding (n = 8 rats/group). Rats fed ad libitum were killed before fasting (control, n = 8). Distal ileal segments (30 cm) were resected for measurement of neurotensin tissue concentration by radioimmunoassay and extraction of poly (A)+ RNA for Northern hybridization with a rat neurotensin complementary DNA probe. Blots were stripped and reprobed for beta-actin as a control for RNA loading. A nuclear run-on transcription assay was performed to determine the relative rate of neurotensin transcription. In the first experiment, neurotensin messenger RNA transcripts of 1.0 and 1.5 Kb sizes were found throughout the small intestine and proximal colon; the greatest abundance was found in the distal small intestine. In the second experiment, neurotensin tissue concentration was significantly reduced with fasting. Refeeding a diet for 24 hours returned neurotensin concentration to control levels. However, neither the amount of neurotensin messenger RNA nor its rate of transcription were altered by fasting and refeeding. These findings suggest that a posttranscriptional mechanism is responsible for regulation of neurotensin synthesis in gut mucosa. PMID- 1858035 TI - Introduction of bias in residency-candidate interviews. AB - We have developed, as part of our resident applicant ranking process, a computerized weighted scoring system incorporating, among other variables, the interview score (IS). This study was undertaken to test the IS as a dependent variable when the applicant file is available during the interview. Over a 3-year period, each of two faculty members interviewed 133 candidates in a "blinded" fashion (file unavailable) or 290 candidates with an "open" file. The mean discrepancy between paired interviewers (1 to 10 scale) was 1.34 +/- 0.10 for the blinded group versus 0.93 +/- 0.06 for the open group (p less than 0.001). Individual and multiple regression analysis were used to test the IS as a dependent variable in the open group, with the blinded group as a control. In each instance (except clerkship grades), the IS correlated more closely with other parameters (p less than 0.05) in the open group. Correlation coefficients were 0.27 (blinded) and 0.64 (open) for weighted scores combining all parameters (p less than 0.001) and 0.39 (blinded) and 0.65 (open) for multiple linear regression analysis (p less than 0.001). We conclude that the IS is significantly influenced if other objective variables are at hand, thus deflating the actual weight of the interview. To accurately quantify the value of the interview, a correction factor must be applied, or, more appropriately, the interview must be conducted blindly. PMID- 1858036 TI - Relation between p53 overexpression and established prognostic factors in breast cancer. AB - The nuclear phosphoprotein p53 is expressed in all normal cells and appears to function in cell cycle regulation. Abnormally high levels of the protein are found in many different types of cancer. In breast carcinoma overexpression of p53 is associated with point mutations within highly conserved regions of the p53 gene. These altered genes encode stable p53 proteins that can be detected by standard immunohistochemical techniques unable to detect rapidly degraded wild type protein. The level of p53 expression in 184 primary breast cancer specimens was assessed by immunohistochemical analysis and related to the following established prognostic factors for breast cancer: age, stage, metastatic involvement, concentration of estrogen and progesterone receptors, proliferative index, and HER-2/neu overexpression. Fifty (27%) of these primary breast cancer specimens had widespread overexpression of p53. Highly significant associations were found between p53 overexpression and late stage, metastatic spread, and low concentration of progesterone receptors. The presence of elevated levels of mutant p53 may itself be a prognostic factor in human breast cancer and activation of this oncogene may be important in the ability of a tumor to metastasize. PMID- 1858037 TI - Evidence for a new tumor-suppressor gene involved in gastrointestinal malignancies. AB - Inactivation or loss of tumor-suppressor genes is believed to lead to the development or progression of malignancies. To determine whether a tumor suppressor gene is located on chromosome 8, DNA was extracted from tumor and normal tissue of colorectal, gastric, and pancreatic specimens, and allele loss was investigated by Southern hybridization techniques with the chromosome 8 probe D8S7. Twenty-five percent of pancreatic carcinomas, 50% of gastric carcinomas, and 50% of colorectal carcinomas were found to have lost an allele on chromosome 8. These findings suggest the presence of a tumor-suppressor gene on chromosome 8, which is involved in colorectal carcinoma, gastric carcinoma, and pancreatic carcinoma. Definition of the frequency with which this tumor-suppressor gene is involved in gastrointestinal malignancies will await the study of many patients who are classified as informative and the use of multiple probes for chromosome 8. PMID- 1858038 TI - The Ca2+ second messenger system and interleukin-1-alpha modulation of hepatic gene transcription and mitochondrial fat oxidation. AB - Cytokines have been implicated in the modulation of fat metabolism after sepsis. Carnitine palmitoyltransferase (CPT), the regulatory enzyme of hepatic mitochondrial long-chain fatty-acid oxidation, is involved in the control of hepatic fat oxidation in sepsis. Using either H4IIe rat hepatoma cells or rat hepatocytes in primary culture, we tested the hypothesis that interleukin-1-alpha (IL-1 alpha) would modulate CPT transcription (CPT mRNA), CPT translation (35S methionine CPT protein incorporation), and hepatic mitochondrial oxidation of 1 Carbon 14-labeled (14C) palmitate to ketone bodies (acid soluble products). We showed that IL-1 alpha significantly increased CPT mRNA, 35S-methionine incorporation CPT protein, and hepatic mitochondrial oxidation of 1-14C-palmitate to acid soluble products. We further hypothesized that the Ca2+ second messenger system may play a role in the IL-1 alpha induction of hepatic CPT gene transcription. We showed that either calcium ionophore (A23187) or phorbol myristate acetate increased CPT gene transcription and that either calcium chelation, protein kinase C inhibition (acridine orange), or chronic exposure to phorbol myristate acetate significantly inhibited IL-1 alpha induction of CPT mRNA. We conclude that the IL-1 alpha increases in hepatic mitochondrial fatty acid oxidation may be, in part, secondary to increased CPT gene transcription and translation and that the Ca2+ second messenger system may play an important role in IL-1 alpha induction of CPT gene transcription. PMID- 1858039 TI - Cytokine modulation of glutamine transport by pulmonary artery endothelial cells. AB - The effects of tumor necrosis factor and interleukin-1 on sodium-dependent glutamine transport by cultured pulmonary artery endothelial cells (PAECs) were studied. Incubation of PAECs with cytokines (10 to 1000 units/ml) resulted in a significant increase in System ASC-mediated glutamine transport that was dose dependent, first observable after 8 hours, and maximal after 12 hours of exposure. Kinetic studies indicated that the increase in carrier-mediated activity was not due to a change in Km (transporter affinity) but instead to a 45% to 75% increase in maximal transport rate (Vmax). The cytokine-stimulated increase in glutamine uptake by PAECs was completely blocked by actinomycin D and cycloheximide, indicating that the accelerated glutamine transport was dependent on de novo RNA and protein synthesis, perhaps of the transporter itself. The data indicate that these cytokines accelerate glutamine uptake by PAECs, either directly or indirectly, a response which may be required to support endothelial metabolism, structure, and function during infection and inflammation. The results of this study represent, to our knowledge, the first reports of cytokine mediated modulation of System ASC activity, a carrier that has historically been unresponsive to hormonal regulation in other tissues. PMID- 1858040 TI - Nitric oxide generation from L-arginine is required for optimal human peripheral blood lymphocyte DNA synthesis. AB - We examined whether L-arginine is a substrate for nitric oxide (NO) production by peripheral blood mononuclear cells (MNC) in vitro. Minimal extracellular arginine (0.04 mmol/L) is required for maximal lymphocyte proliferation after phytohemagglutinin stimulation. In the absence of arginine, proliferation was 41% of normal without loss of viability. In contrast, MNC total protein synthesis (as assessed by tritiated leucine incorporation) or lymphokine synthesis (interleukin 2, as assessed by cytotoxic lymphoid line (CTLL) proliferation) were not affected by the absence or presence of arginine in the medium. Exogenous nitric oxide provided as sodium nitroprusside could replace L-arginine for maximal blastogenic proliferation. The addition of NG-monomethyl-L-arginine (NMMA; 0.1 mmol/L), a specific inhibitor of the NO synthetic pathway, significantly reduced DNA synthesis both at 0 and 0.1 mmol/L arginine concentrations; this effect was reversed to 91% of normal by excess arginine (1.0 mmol/L). Homoarginine (0.1 mmol/L; a known substrate for NO production) partially substituted for arginine, and this effect was also abrogated by NMMA. Nitrite levels (an end product of NO metabolism) were reduced when L-arginine was absent or NMMA was added to L arginine-containing media. Cytosol from phytohemagglutinin-stimulated MNC enhanced cyclic guanosine monophosphate production in the presence of L-arginine as substrate. The data suggest that the inductive effects of L-arginine on MNC DNA synthesis are not related to its nutrient requirement for protein synthesis, but rather caused by its role as a substrate for NO production. MNC actively synthesize NO during mitogenic proliferation. NO appears to be a promoter of MNC DNA synthesis, probably by its well-known effect as an activator of guanylate cyclase, which increases cyclic guanosine monophosphate levels. PMID- 1858041 TI - Nitric oxide synthesis in the in vivo allograft response: a possible regulatory mechanism. AB - Activated macrophages are known to oxidatively metabolize L-arginine to nitric oxide and citrulline. We have recently shown that nitric oxide is a potent inhibitory molecule in the in vitro rat mixed-splenocyte culture, resulting in inhibition of proliferation and cytolytic T-cell induction. We undertook this study using the sponge matrix allograft model in the rat to determine whether nitric oxide plays a role in an in vivo allograft response. Our experiments showed that on day 6 after grafting, when cytolytic activity of allograft infiltrating cells is first detected, allogeneic graft fluid contains higher levels of NO2-/NO3- (the stable endproducts of nitric oxide metabolism) than syngeneic graft fluid. Furthermore, evaluation of the supernatants of cultured graft-infiltrating cells revealed that allogeneic graft-infiltrating cells spontaneously produce higher amounts of nitric oxide than syngeneic graft infiltrating cells. The nitric oxide production was inhibited in the presence of NG-monomethyl-L-arginine (NMA), the competitive inhibitor of nitric oxide production. Most of the nitric oxide production was observed in the adherent macrophage fraction of the allograft-infiltrating cells. When allograft infiltrating cells were cultured in the presence of NMA, donor-specific cytolytic activity was observed, whereas allograft-infiltrating cells cultured in the absence of NMA showed no cytolytic activity. These data show that nitric oxide production may play an important regulatory role in the allograft response. PMID- 1858043 TI - Pentoxifylline restores intestinal microvascular blood flow during resuscitated hemorrhagic shock. AB - We studied the intestinal microvascular blood flow responses to hemorrhage and resuscitation with pentoxifylline by in vivo video microscopy. Male Sprague Dawley rats were hemorrhaged to 50% of baseline mean arterial pressure for 45 minutes and then blindly randomized to receive pentoxifylline (25 mg/kg bolus + 0.2 mg/kg/minute) or an equivalent volume of saline plus return of shed blood and an additional bled volume of Ringer's lactate solution. Hemorrhage caused intestinal microvascular blood flow to decrease to 10% to 15% of baseline values. In the control group, resuscitation restored cardiac output and mean arterial pressure to baseline values, but intestinal microvascular blood flow remained at 30% of baseline values. In contrast, addition of pentoxifylline to the resuscitation regimen resulted in an immediate hyperemic response with an increase in intestinal microvascular blood flow to significantly greater than baseline values followed by return to baseline. Arteriolar dilation was not responsible for the improvement in flow implicating improved flow dynamics between erythrocytes, granulocytes, and vascular endothelia within the microcirculation. We conclude that addition of pentoxifylline to resuscitation from hemorrhagic shock restores intestinal microvascular blood flow. PMID- 1858042 TI - The role of intrarenal prostaglandins and angiotensin II in acute cyclosporine induced vasoconstriction. AB - Cyclosporine causes intrarenal vasoconstriction, which may account for its nephrotoxic effects. In this study we investigated the role of endogenous prostaglandins and angiotensin II in cyclosporine-induced intrarenal vasoconstriction. Split hydronephrotic kidneys in decerebrate rats (n = 16) were suspended in an environmentally controlled tissue bath. Interlobular, afferent, and efferent arteriolar diameters and red blood cell velocity were measured by in vivo video-microscopy and Doppler velocimetry. After topical application of cyclosporine to the kidney in the tissue bath, a 12% +/- 2% constriction of the interlobular and a 28% +/- 5% reduction in interlobular blood flow occurred. The afferent and efferent arterioles also constricted by 13% +/- 2% and 10% +/- 3%, respectively. Prostaglandin inhibition with mefenemate augmented this vasoconstriction (16% +/- 2% at interlobular and 21% +/- 4% at afferent arterioles) and reduction in interlobular blood flow (38% +/- 8%) below baseline values. Mefenemate alone resulted in a 35% +/- 5% reduction in interlobular blood flow, which was not further augmented by cyclosporine. In contrast, local competitive angiotensin II-receptor inhibition with saralasin maintained blood flow after cyclosporine and prevented intrarenal vasoconstriction by cyclosporine. This suggests that prostaglandins protect against intrarenal vasoconstriction and that acute cyclosporine-induced vasoconstriction is mediated through angiotensin II receptors. PMID- 1858044 TI - Pretreatment with a nontoxic derivative of endotoxin induces functional protection against cardiac ischemia/reperfusion injury. AB - We hypothesized that low-dose pretreatment of an intact animal with a nontoxic derivative of endotoxin, monophosphoryl lipid A (MPL), would induce protection against cardiac ischemia/reperfusion (I/R) injury. The purposes of this study were to investigate whether MPL pretreatment would induce functional protection against cardiac I/R injury, to delineate the temporal induction of protection, and to examine antioxidant enzyme induction as a mechanism of protection. Rats were administered a 5 mg/kg dose of MPL at 2 hours and 24 hours before a 25 minute, global, 37 degrees C ischemic insult followed by reperfusion (modified Langendorff). At 40 minutes of reperfusion, ventricular function was assessed (ventricular balloon; developed pressure, rate of contraction, rate of relaxation). Hearts from rats pretreated with MPL 24 hours before isolation exhibited preservation of ventricular function (p less than 0.05). After I/R, hearts from rats pretreated with MPL 24 hours before isolation had increased (p less than 0.05) catalase activity compared to saline pretreated controls and rats pretreated with MPL 2 hours before isolation. We conclude that (1) pretreatment with MPL induces functional protection against cardiac I/R injury, (2) protection (not evident at 2 hours) is maximal at 24 hours, suggesting enzyme induction, and (3) increased catalase activity correlates with the functional protection. PMID- 1858045 TI - Aneurysm or occlusive disease--factors determining the clinical course of atherosclerosis of the infrarenal aorta. AB - Atherosclerosis of the infrarenal aorta results in distinct clinical entities- aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA). Although loss of collagen has been implicated in AAA, collagen accumulation plays a role in AOD. In vivo collagen-gene expression can be assessed using complementary DNA for collagen types I and III alpha-chains. The purpose of this study is to compare total collagen (type I + III) and collagen types I and III messenger RNA in AAA, AOD and normal aorta. Specimens were collected from the infrarenal aorta during operation for AOD (n = 7), AAA (n = 7), autopsy, or organ procurement (normal; n = 7). Northern transfer analysis of total RNA was used to compare mRNA levels for type I and III collagen. After preliminary extraction, specimens were hydrolyzed for hydroxyproline analysis used to calculate total collagen (type I + III). Relative levels of type I (pro-a1[1]) mRNA were greater in both AOD (0.77 +/- 0.35) and AAA tissue (0.94 +/- 0.24; p = 0.6) than in normal aorta (0.02 +/- 0.03). Type III (pro-a1[III]) mRNA levels were also greater in AOD (2.52 +/- 0.19; p = 0.09) and AAA tissue (3.15 +/- 1.3) than in normals (0.97 +/- 0.47). Total collagen concentration was increased in AOD (45.6% +/- 3.1% dry weight; p less than 0.05) but not AAA tissue (27.8% +/- 4%) when compared to normal aorta (34.7% +/- 2.3%). Collagen type I and III gene expression is greater in older, diseased aorta, yet collagen accumulated only in AOD. This implies a similar synthetic response in both AOD and AAA. Thus, proteolytic degradation in AAA appears to determine collagen content and possibly the clinical course of the atherosclerotic process. PMID- 1858046 TI - Diltiazem administration after crystalloid resuscitation restores active hepatocellular function and hepatic blood flow after severe hemorrhagic shock. AB - Studies have shown that active hepatocellular function is depressed after hemorrhagic shock, despite crystalloid resuscitation. It is also known that calcium antagonists produce various beneficial effects on cell and organ function after ischemia and shock. However, it remains unknown whether such agents have any salutary effects on the depressed active hepatocellular function and hepatic blood flow in a nonheparinized model of trauma and hemorrhage. To study this, rats underwent a midline laparotomy (trauma-induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum bleedout was returned in the form of Ringer's lactate. They were then resuscitated with four times the volume of shed blood with Ringer's lactate over 60 minutes, during and after which diltiazem (400 micrograms/kg body weight) was infused intravenously over 95 minutes. Active hepatocellular function (Vmax and Km) was determined with an in vivo indocyanine green clearance technique. Effective hepatic blood flow (EHBF) was determined by Fick principle and corrected by the indocyanine green extraction ratio. Hepatic microvascular blood flow (HMBF) was measured by laser Doppler flowmetry. Results indicate that Vmax, Km, EHBF, and HMBF decreased significantly at 1.5 and 4 hours after resuscitation. Diltiazem infusion restored the depressed Vmax, Km, EHBF, and HMBF and prevented the occurrence of hepatic edema. Thus, diltiazem may be a useful adjunct in the treatment of trauma and severe hemorrhage even in the absence of blood resuscitation. PMID- 1858047 TI - Red cell deformability is an early indicator of infection. AB - Red blood cells (RBC) have been shown to become less deformable during infection. The RBC deformability index (DI) was measured within 24 hours of admission in 37 patients who had suffered trauma and every 48 to 72 hours thereafter while they were in the surgical intensive care unit to assess whether DI could be used as an early indicator of infection after injury. Infection was defined as a temperature of 101 degrees F or more and a white blood cell count of more than 12,000/cm3 associated with a positive culture. Eighteen patients developed an infection, and 19 patients did not. On day 1, both groups showed a significant decrease in DI, compared to controls (0.33 +/- 0.18 and 0.34 +/- 0.25 for patients with infection and patients with no infection vs 1.52 +/- 0.12 for control volunteers; p less than 0.05). In the group with no infection, the DI improved in 16 of 19 patients after injury; the DI in patients with infection continued to decrease in 17 of 18 patients. The decrease in DI occurred 4 +/- 2 days (range, 2 to 8 days) before the diagnosis of infection. No significant differences were apparent in the absolute white blood cell count between the group with infection and the group with no infection at any time after injury. Differences in maximal temperature were noted on day 3 and beyond; however, 30% of patients with no infection had a temperature of more than 101 degrees F for 7 days. These data show that trauma results in a significant decrease in RBC deformability and that serial changes in DI appeared to predict which patients would develop an infection and which patients would recover uneventfully. RBC deformability may be helpful in early detection of infection in patients who have suffered trauma. PMID- 1858048 TI - The impact of a resident-directed survey on the education curriculum of a university surgical training program. AB - Surgical training programs use various objective and subjective means to evaluate housestaff performance. However it is less clear how to assess the quality of the educational experience the program itself provides. This study examines the use of a resident-directed survey as a means of identifying and rectifying weakness in a surgical training curriculum. Multiple choice questionnaires covering each of 14 senior rotations were prepared by chief residents and distributed to all senior surgical residents in April 1989 (year I). The survey covered factors considered vital to resident education, including operative experience, input into preoperative and postoperative decisions, autonomy, and time demands, and an overall rating (OR) of the educational quality of the rotations. Responses were numerically graded: 1, appropriate; 0, fair; -1, inadequate (or "excessive" for the variable "time demands"). The results, which were presented and discussed at a departmental retreat that spring, prompted specific curriculum changes for the 1989-1990 academic year. An identical survey was conducted the next spring (year II). Major reorganizational changes were made in three of the four negatively rated rotations from year I. The OR for each of the rotations improved dramatically in year II (average increase of 0.64/rotation; p less than 0.05). None of the eight favorably rated rotations in year I suffered a reduction in OR as a result of the changes. Case load, intraoperative involvement, and input in both preoperative and postoperative decisions correlated most frequently with favorable ORs in both years. This study shows that a resident survey is an effective tool for critically assessing the education curriculum of a surgical training program. PMID- 1858049 TI - Pathways of serotonin-induced electrolyte transport in rat distal colon. AB - Serotinin-stimulated electrolyte transport was examined in flat-sheet preparations of rat left colon with the Ussing chamber-voltage clamp technique. Transport was studied in tissues stripped of muscularis propria and in nonstripped tissue. In nonstripped colon, the action of serotonin (5 hydroxytrytamine [5-HT]) on short-circuit current was inhibited by a factor of 60% by tetrodotoxin (P less than 0.05; t test) and was also inhibited by the 5HT2 antagonist ketanserin (p less than 0.05 vs serotonin; t test) and the 5-HT3 antagonist ICS 205-930 (p less than 0.05 vs serotonin, t test). These compounds produced corresponding inhibition of serotonin-induced sodium and chloride flux in this preparation. The tetrodotoxin-sensitive component was not inhibited by atropine, hexamethonium, phentolamine, or propranolol. Histologic analysis of the stripped preparation showed that it consisted of mucosa and musclaris mucosa only. In this stripped preparation, serotonin-induced change in short-circuit current was tetrodotoxin insensitive and inhibited by ketanserin (p less than 0.05 vs serotonin, t test) but not by ICS 205-930. Serotonin-induced sodium and chloride flux was inhibited by ketanserin in the presence of tetrodotoxin in this preparation. These results suggest that serotonin-induced electrolyte transport in rat distal colon is mediated by nonneural 5HT2 receptors in the mucosa or muscularis mucosa and by 5-HT3 receptors located on enteric nonadrenergic, noncholinergic nerves. PMID- 1858050 TI - Capsaicin-sensitive nerves mediate esophageal mucosal protection. AB - The esophageal mucosa is exposed to damaging agents both by ingestion and reflux. Using our in vivo rabbit model of esophagitis, we have observed that acute luminal exposure (within 1 to 5 minutes) to potentially harmful agents, such as acid, bile, or ethanol, induces a rapid increase in mucosal blood flow; whereas prolonged exposure (10 to 60 minutes) results in mucosal injury and ablation of blood flow. We have also shown that capsaicin-sensitive mucosal afferent nerves can modulate esophageal blood flow. These findings led us to hypothesize that the reactive increase in blood flow induced by luminal agents represents a mechanism of protection mediated by capsaicin-sensitive nerves. The objective of these experiments was to determine if luminal capsaicin, a specific probe for visceral afferent nerves, could both preserve mucosal blood flow and protect against ethanol injury. Rabbits were subjected to luminal instillation of 50% ethanol with or without 1% capsaicin. Blood flow was measured with microspheres at baseline and after 2 and 10 minutes. Rabbits exposed only to ethanol developed severe mucosal injury coincident with near ablation of mucosal blood flow. In contrast, rabbits exposed to ethanol with capsaicin showed protection of the epithelium with a sixfold increase in mucosal blood flow. We conclude that capsaicin-sensitive nerves in the esophagus are local effectors of mucosal protection by virtue of preserving blood flow. PMID- 1858051 TI - Autotransplantation of dispersed pancreatic islet tissue combined with total or near-total pancreatectomy for treatment of chronic pancreatitis. AB - Chronic pancreatitis is difficult to treat in patients with a nondilated duct. Patients experiencing intractable pain unresponsive to or judged untreatable by lesser procedures must decide between total pancreatectomy and resultant diabetes or a continuation of their pancreatitis. From 1977 through 1990, 26 patients underwent extensive pancreatectomy and dispersed pancreatic islet tissue autotransplantation for treatment of chronic pancreatitis pain and prophylaxis of surgical diabetes. Of these 26 patients, total (Whipple) or near-total (greater than 95%) pancreatectomy was performed in 24 patients. Of these 24 patients, pain relief could be assessed in 21 patients at 5 to 155 months (mean, 5.7 years), and 19 patients (90%) reported partial or complete remission. Of the patients who underwent total or near-total pancreatectomy, islets were injected intraportally in 22 patients and into the renal subcapsule in two patients. The latter two patients have required insulin since surgery. Of the other 22, one patient died from a complication of the pancreatectomy. Nine of the 21 evaluable recipients of intraportal islet autografts were insulin independent for at least several months after surgery. Five patients are currently insulin independent at 6 years, 4 years, 1.5 years, 9 months, and 5 months after surgery. Of the other four patients, one patient died insulin independent at 6 years, and three patients required insulin beginning 8 to 18 months after surgery. Insulin independence correlated with the number of islets recovered, which in turn correlated inversely with the degree of pancreatic fibrosis. Of our four most recent patients, three patients had mildly to moderately fibrotic glands, and higher numbers of islets were obtained. After total (Whipple) pancreatectomy, these three patients are insulin independent. A liver biopsy was performed in one patient 8 months after total pancreatectomy and islet autotransplantation; numerous clusters of islet cells staining strongly for insulin and glucagon were detected within portal triads on both wedge and needle biopsy specimens. Morbidity related to the intraportal-dispersed pancreatic islet tissue transplantation was low (no disseminated intravascular coagulation, significant portal hypertension, or hepatic dysfunction). Islet autotransplantation can be an effective and safe adjunct to extensive pancreatic resection for those patients who risk surgical diabetes for relief of their chronic pancreatitis pain. PMID- 1858052 TI - Insights into the mechanisms of defective antigen presentation after hemorrhage. AB - Although hemorrhage depresses macrophage antigen presentation (AP), a critical component in eliciting an antigen-specific immune response, it is not known which particular step in macrophage AP (i.e., uptake, ingestion, catabolism, or presentation of degraded antigens to T cells) is defective. To study this, C3H/HeN mice were bled to an arterial mean blood pressure of 35 mm Hg, maintained for 60 minutes, and then adequately resuscitated. Peritoneal and splenic macrophage cultures were prepared 2 and 24 hours after hemorrhage. Macrophage AP capacity was measured by coculturing macrophages with the T-helper cell clone D10.G4.1. To gain information about macrophage ability to digest the specific antigen conalbumin, lysosomal activity was bypassed by use of chemically denatured conalbumin peptides. To study macrophage ability to present conalbumin peptides, macrophages were fixed and D10.G4.1 proliferation in response to fragmented conalbumin was determined. AP of native conalbumin by peritoneal macrophages and splenic macrophages was depressed (p less than 0.05) by 50% (peritoneal macrophages) and 55% (splenic macrophages) 2 hours and 57% (peritoneal macrophages) and 35% (splenic macrophages) 24 hours after hemorrhage. In contrast, presentation of conalbumin peptides was only slightly decreased. In addition, the ability of fixed peritoneal macrophages and splenic macrophages to present conalbumin peptides was similar in hemorrhaged and sham mice. Because bypassing of macrophage lysosomal activity with degraded native antigens prevented the suppression of AP, the results suggest that hemorrhage-induced suppression of AP is not caused by a reduced macrophage capacity to present antigenic peptides but by decreased antigen catabolism by macrophages. PMID- 1858054 TI - [Psychosomatic approach to orofacial pain and its equivalents. Study of 53 cases at the Oral Medicine Department, E.S.M.D., Lisbon]. PMID- 1858053 TI - Wound fluid amino acid concentrations regulate the effect of epidermal growth factor on fibroblast replication. AB - Growth factors and amino acids (AA) are required for cell proliferation. A comparison of the AA composition of wound fluid (WF) to that of Eagle's medium reveals that AA in WF may be limiting to cell replication. Yet WF supports fibroblast replication and stimulates AA uptake. Epidermal growth factor (EGF) stimulates fibroblast replication and stimulates human wound healing when applied topically. We evaluated the interactions between EGF and AA concentrations found in WF. Wound fibroblasts were cultured in media prepared to mimic the AA concentrations found in WF on days 1, 5, and 10 and in the presence of varying concentrations of EGF. Fibroblasts cultured in all three experimental media showed a dose response to EGF for both tritiated-thymidine uptake (proliferation) and AA uptake. The fibroblast proliferation in response to EGF was augmented by the AA composition of day-5 WF. These data show a dose-dependent effect of EGF on fibroblast replication and AA uptake in the absence of serum that is augmented by the particular AA combination found in day-5 WF and suggests that an optimal physiologic AA profile may aid in EGF stimulation of wound fibroblast replication. PMID- 1858055 TI - [Review of the problems of prosthetic crowns]. PMID- 1858056 TI - [Marginal leakage of amalgam restorations]. AB - The authoress presents a revision work on a marginal microleakage around amalgam restorations. After a brief introduction in which some harmful aspects of its formation are made clear, a reference to the causes and tooth prevention against its formation follows. PMID- 1858057 TI - [Angina bullosa haemorrhagica: clinical case, review of the literature]. PMID- 1858058 TI - [Physiology of autotransplants in the human species. Histological analysis of transplanted upper canine pulps]. AB - 10 canine pulps were examined after transplantation. The time of transplant life was not the same in all cases, so it was possible to record all the evolutive patterns during 2 months. Correlating our observations with literature and statistics, it was possible to draw the main aspects of transplant pulp physiology. PMID- 1858059 TI - [A case of appendicular supplementary root with external root resorption]. AB - The case of a lateral maxillary incisor with a supplementary root fractured by external root resorption, is presented. The role played for the periodontal disease is shown in the clinical and radiographic achievements, and their implications in the pulpal disease. Endodontic therapy was performed and the diagnosis confirmed in the specimen histological research. PMID- 1858060 TI - [Changes in prevention of infection: a historic retrospect]. AB - The discovery of pathogenic microorganisms in the mid 19th century made possible an effective prophylaxis on a scientific basis. During many centuries, sequestration of leprous in specific dwellings was the custom; in the hindsight it proved to be instrumental for the almost complete disappearance of leprosy in Europe. This was also the case with the epidemics of plague, which, since the late Middle Ages, were stopped by measures of quarantine in ports and at frontier passages (e.g. Austrian plague-cordon). The beginning of internationally coordinated health measures was equally decisive. With smallpox, the variolation (since 1730) gave first relief, until Sir Edward Jenner discovered in 1798 the highly successful cross-immunity through vaccination. The development of sanitary conditions through better drinking-water supply, canalization and garbage disposal since the mid 19th century contributed much to the betterment of health, especially concerning cholera epidemics in cities. The reinforcement of the individual hygiene (body care, extermination of lice, antiseptic treatment of wounds, etc.) helped to achieve an adequate prevention and, together with intensified health education, a decline of infectious diseases in general. PMID- 1858061 TI - [Skin and hand disinfection]. AB - In modern medicine, hygiene has become an issue of ever increasing importance. Disinfection of hands is crucial, since hands are the main vector of bacteria. Successful disinfection depends not only on the appropriate choice of an active agent, but equally so on proper techniques and skin care. The spectre and the time profile of activity as well as the skin-protecting properties of the chosen disinfectant must be known. Basic knowledge of disinfection is necessary for a rational interpretation of the information given in the glossy printed material of advertisement. PMID- 1858062 TI - [Public health and isolation measures with regard to infectious patients]. AB - Patient isolation aims at reducing the risk of infection transmission to other patients and the hospital personnel. Three types of disease-specific isolation procedures and their indications are described: strict isolation, respiratory isolation and enteral isolation. The type of patient isolation to be applied depends on the mode of pathogen transmission and on the severity of the disease it produces. PMID- 1858063 TI - [Preventive use of antibiotics for internal medicine diseases]. AB - Prevention of infection by the interniste is less explored than perioperative prophylaxis. Basically, prophylaxis in internal medicine may be considered in the following situations: in case of chronic recurrent infections, in case of persisting infections, after contact with a dangerous microorganism, after contact with a potentially infectious vector, during bacteremia or in case of an anatomical defect. For some of these situations (malaria, tuberculosis, rheumatic fever) clear guidelines exist which, however, are rather based on the consensus of experts than on scientific data. For other diseases (e.g. chronic recurrent urinary tract infections) clinical studies are the basis for a rational proceeding. For a third group of situations (e.g. Lyme disease, chronic bronchitis, leak of cerebrospinal fluid, implant) neither guidance nor sufficient clinical data exist. In these cases the proceeding is individual. The basis for the decision is given by clinical observations, single studies, theoretical considerations or cost-benefit analyses. PMID- 1858064 TI - [Antibiotic prevention of bacterial endocarditis]. AB - Infective endocarditis is a serious disease and should be, if possible, prevented. Two risk groups are classified in relation to the patient's underlying cardiac lesions. At high risk are patients with prosthetic valves or with a previous infective endocarditis. Patients with congenital and acquired heart disease, mitral valve prolapse with regurgitation and hypertrophic obstructive cardiomyopathy are at moderate risk. Patients of these two groups should receive antibiotic prophylaxis before dental or surgical procedures that cause bacteremia. For patients at moderate risk a single dose of an orally administered antibiotic should be given one hour before the procedure (e.g. amoxicillin 3 g for procedures of the oropharyngeal, gastrointestinal or genitourinary tract, where the causitive agents of endocarditis are Viridans streptococci or enterococci). Multiple doses are recommended for patients at high risk. The combination of amoxicillin and gentamicin (vancomycin and gentamicin in penicillin-allergic patients) offers the widest margin of safety in high-risk patients. PMID- 1858065 TI - [Active and passive immunization: 1991 status]. AB - Contrary to the regular immunization schedule for children, the majority of immunization are done in adulthood in case of special risks only, such as old age, chronic illness or exposure. The protection against a variety of communicable diseases has to be monitored and if necessary to be boosted regularly. Based on the routine vaccination scheme 1991 of the Federal Department of Public Health, the following vaccinations which are commercially available in Switzerland are discussed in this review: diphtheria, Haemophilus influenzae, hepatitis B, influenza, measles + mumps + rubella, meningococci, pertussis, pneumococci, poliomyelitis, tetanus, rabies, tuberculosis, varicella and tick encephalitis. Furthermore, the current recommendations are given for the prophylactic and therapeutic use of immunoglobuline preparations. PMID- 1858066 TI - [Prevention of infectious diseases in traveling]. AB - Diarrhea, malaria, and viral hepatitis are among the preventable diseases of travellers. In Switzerland, almost all serious cases of malaria are introduced from tropical Africa; therefore, we recommend protection with 250 mg of mefloquin per week for this destination. Elsewhere, protection against mosquitoes, in combination with Fansimef for self-treatment, may be enough. For travellers' diarrhea, we prefer immediate treatment with ciprofloxacin or cotrimoxazol to prophylaxis. Administration of immune globulin against hepatitis A may be recommended for all non-immune tourists, whereas protection against hepatitis B is necessary for health workers and sex tourists. PMID- 1858067 TI - [Primary prevention of HIV infection]. AB - Primary prophylaxis by a change of behaviour in the population continues to be the only effective possibility to prevent a further spread of the aids epidemic. The most important presupposition for this is the precise knowledge of the ways of transmission and the corresponding protective measures. Informations referring to this must turn up repeatedly and above all free of contradictions at all levels of the preventive campaign. The desired changes of behaviour suppose also a climate of confidence and solidarity. The physician's task of prevention is part of the comprehensive strategy of HIV-prevention in Switzerland (effect in width and depth on population- and target groups and on the individual level). It is naturally the physician's domain to look after and counsel individually. Most variable possibilities of beginning a conversation about Aids prevention offer themselves to him. He should put the indication for this as generous as possible and deal extensively with a possible risky behaviour which might not be conscious to both the patient and the physician. The HIV antibody test is indicated in certain situations, however the pre- and posttest counselling is in any case much more decisive than the result of the test. The preventive measures recommended up to now for the most important ways of transmission (sexual contact, intravenous drug use, perinatal transmission, blood/blood products) are still valid without modification. PMID- 1858068 TI - [Secondary prevention in HIV infection]. AB - In HIV seropositive persons, secondary prophylaxis should prevent HIV-associated diseases, including opportunistic and other complications, and delay progression of HIV infection. Efforts to control transmission of secondary infections are of limited value, since these complications are mainly caused by endogenous opportunistic microorganisms. Vaccines are currently available for only a few of the pathogens that are potentially important in this clinical setting; they include influenza, Streptococcus pneumoniae and hepatitis B. However, antibody responses to these vaccines may be unsatisfactory in immunocompromised persons. Chemoprophylactic regimens have been devised primarily for prevention of Pneumocystis carinii pneumonia and tuberculosis. Recently, antiretroviral therapy with zidovudine has shown promise in delaying progression of AIDS in asymptomatic HIV seropositive individuals with impaired cellular immunity. PMID- 1858069 TI - Observations with Anteovin in relation to age. AB - Anteovin biphasic contraceptive tablet has been used in adolescent and middle aged women for contraception. Attempts were made with the tablet for the treatment of climacteric complaints. The tablet was found to be effective in both fields. References dealing with borderline cases and present interest in the question have been discussed. The author points out the importance of further analyses. PMID- 1858070 TI - Long term use of piroxicam in the treatment of systemic lupus erythematosus. AB - Twelve patients suffering from systemic lupus erythematosus (SLE) were treated with piroxicam (Hotemin-EGIS) for 9-18 (mean: 13.7) months. At the beginning, the patients were in a moderately active stage of the disease, 10 patients also received low dose corticosteroid treatment. After the study was completed, clinical and immunological improvement was seen in 10 cases. The average daily dose of prednisolone could be reduced (from 10.5 mg to 5 mg). These patients tolerated the treatment well, no adverse effect was seen. No elevation of serum transaminase, creatinine or change in blood cell count and glomerular filtration rate were observed. Piroxicam, therefore, is recommended for the treatment of mildly active SLE. PMID- 1858071 TI - Klion in the prevention of early complications following appendectomy. AB - The authors observations with prophylactic administration of metronidazole manufactured by the Gedeon Richter Company, Hungary (trade mark Klion) in children with phlegmonous appendicitis are reported. The drug was administered in three doses to 51 children. Results of bacteriology could be assessed in 42 children. The results of prophylactic administration of Klion in phlegmonous appendicitis were excellent. In our group there were no inflammatory wounds and/or intraperitoneal complications. For comparison, in a cohort of 1.008 children with phlegmonous appendicitis, without prophylaxis the rate of inflammatory complications was 3.62%. Klion has minimal side effects and is well tolerated and seems to be a superb drug for prophylaxis. PMID- 1858072 TI - The medical aspects of doping. AB - One of the crucial problems in the competitive sports of our days is the illicit use of drugs in increasing physical performance. The moral, professional, and legal responsibility of the physicians having a role in doping is quite explicit. Sports medicine can significantly contribute to the repression of doping; due to the diverging interests, however, it will not be able to solve it alone. The paper reviews the development and background of doping and, relying on the list issued by the International Olympic Committee, on banned drugs discusses the intended and adverse effects of the drug classes used for doping. Cases of doping detected at the Seoul Olympic Games are presented and a brief survey is given of the means that should be used for check-up. PMID- 1858073 TI - Thrombosis prophylaxis with subcutaneous heparin Ca injection in the course of caesarean sections. AB - Subcutaneous low-dose Heparin Ca injections were given as prophylactic treatment to 31 women who were candidates for Caesarean section and were at high risk of thrombo-embolism. Postoperative deep vein thrombosis or pulmonary embolism did not occur in the treated cases. Local or systemic haemorrhages or other reactions were not observed. The controlled haematological parameters changed as expected. According to the opinion of the authors Heparin Ca may be successfully used for the prevention of the postoperative complications of Caesarean section. PMID- 1858074 TI - Protective role of lipanthyl in women taking oral contraceptives. AB - Fenofibrate subdoses were applied as an adjuvant therapy in 64 women for improving lipid metabolism. The women took different oral contraceptives mainly with progestin dominance and the prevention of the unfavourable metabolic effects with drug therapy was indicated for maintaining safe contraception which was absolutely necessary for health and other reasons. Protective Lipanthyl therapy seemed to be very useful for this purpose. PMID- 1858075 TI - Polish health conditions in Hungary during World War II. PMID- 1858076 TI - Vocal cord dysfunction and wheezing. PMID- 1858077 TI - Prevalence of asthma among 12 year old children in New Zealand and South Wales: a comparative survey. AB - A survey of 12 year old schoolchildren was carried out in New Zealand and South Wales, the same questionnaire and exercise provocation test being used. The prevalence of a history of asthma at any time was higher in New Zealand (147/873, 17%) than in South Wales (116/965, 12%). The New Zealand children were also more likely than the Welsh children to have a history of "wheeze ever" (27% versus 22%), and wheeze brought on by running (15% versus 10.5%). The sex ratio of asthmatic and wheezy children was very similar in the two countries. A history of hospital admission for chest trouble was twice as common in New Zealand as in South Wales. An exercise test produced a fall in peak expiratory flow rate of 15% or more in more New Zealand children (12.2%) than Welsh children (7.7%). These results suggest that the prevalence of childhood asthma is higher in New Zealand than in South Wales. PMID- 1858078 TI - Recovery of the human immunodeficiency virus from fibreoptic bronchoscopes. AB - Ten bronchoscopes that had been used on patients with the acquired immunodeficiency syndrome were sampled to determine the nature and extent of microbial contamination. Samples were taken by irrigating the suction biopsy channel with modified viral transport medium and by swabbing the insertion tube. Sampling was repeated after they had been cleaned in detergent and after two minutes' disinfection in 2% alkaline glutaraldehyde. Before being cleaned the seven bronchoscopes tested by polymerase chain reaction were contaminated with the human immunodeficiency virus, though infectivity and antigen assays gave negative results. Other organisms identified were hepatitis B virus (1), commensal bacteria (9), and Pneumocystis carinii (4). Mean bacterial contamination was 2.27 log colony forming organisms per millilitre. Cleaning the bronchoscope before disinfection removed all detectable contaminants with a reduction in bacterial growth of up to 8 log colony forming units/ml. PMID- 1858079 TI - Cephalometric measurements in snorers, non-snorers, and patients with sleep apnoea. AB - Cephalometry is often used to assess patients with sleep apnoea but whether these measurements differ from those in non-apnoeic snorers and how they are influenced by age is not clear. Cephalometric radiographs of patients with sleep apnoea were compared with those of snorers without sleep apnoea and those of non-snorers. Fifty two snorers with suspected sleep apnoea had a conventional sleep study and were divided into two groups: those with an apnoea-hypopnoea index greater than 10/h (n = 40, sleep apnoea group) and those whose apnoea-hypopnoea index was 10/h or less (n = 12, snorer group). The cephalometric measurements in these patients were compared with those of 34 non-snoring control subjects. Controls were subdivided into two groups: control group 1 included 17 subjects similar in age to the sleep apnoea and snorer groups (mean (SD) age 50.0 (10.9), 50.7 (9.4), and 50.6 (9.7) years); control group 2 included 15 young men (25.4 (2.6) years). The distance from the mandibular plane to the hyoid bone (MP-H) and the length of the soft palate were greater in the patients with sleep apnoea (28.7 (7.8) and 43.6 (5.0) mm) than in the snorers (23.7 (4.2) and 40.3 (4.9 mm). The MP-H was similar in snorers and age matched control subjects, but was significantly greater in the older than in the younger control subjects (22.1 (6.1) vs 17.0 (6.8]. The soft palate was longer in subjects who snored (both sleep apnoea patients and snorers) than in control subjects. The MP-H distance significantly correlated with age for all subjects (snorers and controls) and for the control subjects alone. This study shows that non-apnoeic snorers have cephalometric abnormalities that differ from those of patients with sleep apnoea and that cephalometric values are influenced by the subject's age. PMID- 1858080 TI - Pulmonary function in chronic renal failure: effects of dialysis and transplantation. AB - Many possible pulmonary complications of renal disease have been described, but little is known of their physiological importance or the effects on them of different forms of renal replacement therapy. Four groups were recruited, each containing 20 patients. The groups consisted of patients with chronic renal failure before dialysis (group 1); patients receiving continuous ambulatory peritoneal dialysis, never having received a transplant (group 2); patients receiving haemodialysis, never having received a transplant (group 3); and patients after their first successful cadaveric renal transplant (group 4). All were attending the same regional dialysis and transplant unit. None was known to have clinically important lung or chest wall disease. Flow-volume loops were recorded before and after 400 micrograms of salbutamol, and plethysmographic lung volumes and airway conductance and single breath carbon monoxide transfer factor were measured. Only nine of 80 patients had normal lung function. The reductions in spirometric values were minor. Whole lung carbon monoxide transfer factor was reduced in all groups (mean % predicted with 95% confidence intervals: group 1 81.7% (74-89%); group 2 69.7% (62-77%); group 3 87.5% (80-96%); group 4 82.5% (78 87%]. The values were significantly lower in those having continuous ambulatory peritoneal dialysis (group 2). Residual volume was reduced significantly in the group who had undergone renal transplantation (85.7%, 77-94%). There was no correlation between these changes and smoking habit, age, duration or severity of renal failure, duration of treatment, or biochemical derangement. It is concluded that abnormal lung function is common in renal disease. The main change is a reduction in carbon monoxide transfer that persists after transplantation. The likeliest explanation is that subclinical pulmonary oedema progresses to fibrosis before transplantation. The fibrosis may worsen further to cause the reduced residual volume in the recipients of grafts. PMID- 1858081 TI - Asbestos induced pericardial effusion and constrictive pericarditis. AB - The number of disorders attributable to asbestos exposure has increased gradually over the years. The latest to be recorded is pericardial effusion and constrictive pericarditis, and three cases are reported here. A man with bilateral pleural thickening and plaques developed acute pericarditis and an effusion and was treated by pericardiectomy. Two men died from constrictive pericarditis associated with bilateral pleural effusions and diffusion pleural thickening. The pericardium showed nonspecific fibrous thickening. All had been occupationally exposed to asbestos. In the fatal cases the lungs contained amphibole fibres, in keeping with a modest degree of occupational exposure. Asbestos produces progressive fibrosis of the pericardium that is similar to diffuse pleural thickening and may be fatal. Both conditions may develop after relatively short or light exposure. PMID- 1858082 TI - Use of transcutaneous oxygen tension, arterial oxygen saturation, and respiratory resistance to assess the response to inhaled methacholine in asthmatic children and normal adults. AB - Respiratory resistance (Rrs6), transcutaneous oxygen tension (PtcO2), and oxygen saturation (SaO2) were measured during methacholine challenge in 15 asthmatic children and six normal adults. During bronchoconstriction, induced by a wide range of inhaled methacholine concentrations (0.5-256 g/l), the rise in Rrs6 was reflected by a fall in PtcO2 in all subjects. Although there was a significant mean fall in SaO2 at maximum bronchoconstriction there was no consistent relation between changes in SaO2 and Rrs6. The inhaled dose of methacholine causing a 40% increase in Rrs6 (PD40Rrs6) and a 20% fall in PtCO2 (PD20PtcO2) was calculated for each subject. There was no significant difference in mean PD40Rrs6 and PD20PtcO2, and the relation between the two was similar in the asthmatic children and the normal adults. It was therefore concluded that the measurement of PtcO2, but not SaO2, during methacholine challenge can be used for the assessment of bronchial responsiveness, and that it could prove particularly useful for children too young to cooperate with lung function tests. PMID- 1858083 TI - Current trends in tuberculosis mortality in England and Wales. AB - To determine current trends in mortality from tuberculosis according to age the published data on notification and deaths from tuberculosis from 1974 to 1987 have been analysed. The ratio of deaths to notifications per year was assessed over this period as a measure of case fatality from tuberculosis. The mean annual decline in the ratio for each age group was as follows: 0-14 years 6.7% (95% confidence interval 4.00 to 9.6%), 15-34 years 1.4% (-0.2 to 3.0%), 35-54 years 4.5% (2.2 to 6.9%), 55-74 years 2.8% (1.8 to 3.7%), and 75+ years 3.2% (2.1 to 4.2%). Because the incidence of disease in the 75+ group has declined much more slowly than in the rest of the population and because the size of this age group has increased in relation to the other groups, the overall annual mortality from tuberculosis has declined by only 0.13% (95% CI -1.3 to 1.3%). The total number of deaths from tuberculosis declined from 996 in 1974 to 430 in 1987, whereas deaths in the 75+ age group remained relatively constant at around 200 a year. PMID- 1858085 TI - Effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid on tracheobronchial clearance in normal human airways. AB - 15-(s)-Hydroxyeicosatetraenoic acid (15-HETE) is the predominant metabolite of arachidonic acid in normal and asthmatic human airways and a potent mucus secretagogue in canine and human airways. A study was carried out on the effect of inhaled 15-HETE on tracheobronchial clearance, measured for six hours by a radioaerosol technique, in 10 normal subjects. Subjects inhaled 80 nmol 15-HETE or the diluent (sodium phosphate buffer) on two occasions at least two weeks apart in a double blind and randomised fashion (20 minutes after radioaerosol inhalation. Tracheobronchial clearance after inhaled 15-HETE was almost identical to that after placebo for all measurements up to six hours. It is concluded that 15-HETE has no effect on tracheobronchial clearance in normal human airways and is unlikely to account for the impaired mucociliary clearance seen in asthma. PMID- 1858084 TI - Participation of the cysteinyl leukotrienes in the acute bronchoconstrictor response to inhaled platelet activating factor in man. AB - To determine whether the effects of platelet activating factor on the airways may be due to the production of leukotrienes we studied the effects of pretreatment with the selective cysteinyl leukotriene antagonist SK&F 104353-Z2 on the airway and cellular responses to inhaled platelet activating factor. Eight healthy men were studied in a randomised, double blind placebo controlled cross-over study. A single dose of platelet activating factor that caused a fall of at least 35% in specific airways conductance (sGaw) was determined initially for each subject. Challenge with this dose of platelet activating factor was then carried out on two further occasions after pretreatment with a single nebulised dose of SK&F 104353-Z2 or placebo. The % reductions in specific airways conductance and of partial flow at 30% of vital capacity (PVmax30) were less after SK&F 104353-Z2 than after placebo (22 versus 34 for sGaw, 19 versus 31 for PVmax30). The mean (95% confidence limits (CL] differences in the maximum % fall from control values for SK&F 104353-Z2 and placebo were -12.6 (-23.8, -1.4) for sGaw and -12.5, ( 20.8 -4.2) for PVmax30. The mean % fall in neutrophil count was similar after SK&F 104353-Z2 (46%) and after placebo (50%) (95% CL of difference 13.6, 6.6). Bronchial responsiveness to methacholine did not increase above baseline values in any subject when measured two weeks after challenge by platelet activating factor. This study suggests that leukotrienes play a part in the response to platelet activating factor in man. PMID- 1858086 TI - Arterial desaturation in HIV positive patients undergoing sputum induction. AB - Arterial oxygen saturation (SaO2) was monitored continuously during and immediately after sputum induction in 41 HIV positive patients with respiratory symptoms and in 20 symptomless medical and nursing staff, who acted as control subjects. Arterial oxygen desaturation (defined as SaO2 less than or equal to 92%) occurred during sputum induction and persisted for up to 20 minutes after the end of the procedure in 11 of the 20 patients with Pneumocystis carinii pneumonia and in nine of the 21 patients with other respiratory diagnoses. None of the control subjects showed oxygen desaturation. Neither the severity of chest radiographic abnormalities, the alveolar-arterial oxygen gradient (both measured before sputum induction), nor baseline SaO2 prospectively identified the patients who developed oxygen desaturation. Two patients, one with pneumocystis pneumonia, developed dyspnoea and had a fall in arterial oxygen saturation to 84% within 10 minutes of starting sputum induction. The procedure was abandoned in both patients and in two further patients, who developed severe nausea and reaching but no oxygen desaturation. Sputum induction in HIV positive patients with respiratory symptoms may induce a fall in SaO2 that persists after this procedure. This may be important if other procedures are performed soon after sputum induction. PMID- 1858087 TI - Statistics in respiratory medicine. 2. Repeatability and method comparison. PMID- 1858088 TI - Nasal intermittent positive pressure ventilation in the treatment of respiratory failure in obstructive sleep apnoea. PMID- 1858090 TI - Malignant pleural effusion in chronic myelomonocytic leukaemia. PMID- 1858089 TI - Left bronchial isomerism associated with bronchomalacia, presenting with intractable wheeze. AB - The cause of the Williams Campbell syndrome (bronchomalacia with bronchiectasis) is controversial. A boy with bronchomalacia, bifid ribs, and left bronchial isomerism presented with intractable wheeze mimicking asthma. The combination of the abdominal, bronchial, and atrial anatomy seen in this child has been described only once previously. The coexistence of these congenital abnormalities in this boy supports a congenital cause for the Williams Campbell syndrome. The need to assess wheezy children critically is emphasised. PMID- 1858091 TI - Radiation associated malignant pleural mesothelioma. AB - Malignant pleural mesothelioma of epithelial type developed in a 24 year old woman, 20 years after radiotherapy for Hodgkin's disease. This case and a review of published cases indicate that radiation may induce malignant mesothelioma. PMID- 1858092 TI - Wegener's granulomatosis simulated by a T cell lymphoma of the lung. PMID- 1858093 TI - Local anaesthesia for fibreoptic bronchoscopy. PMID- 1858094 TI - Lung function 8-18 years after intermittent positive pressure ventilation for hyaline membrane disease. PMID- 1858095 TI - [Skeletal development in the dog in relation to nutrition]. AB - Growth hormone (GH) and insulin-like growth factor I (IGF-I) play important roles during growth, including effects on enchondral ossification. GH plasma concentration is strongly influenced by the nutritional status of the dog. Fasting induces a non-responsiveness of the liver to GH, leading to a decrease in IGF-I release by the liver and a delay in growth. Overfeeding leads to abnormal skeletal development, i.e., osteochondrosis and hip dysplasia. Subnormal plasma concentrations of sex hormones lead to a delay in physiologic epiphysiodesis, whereas high levels of sex steroids may induce premature physeal closure. Dietary calcium, phosphorus, and vitamin D are important factors in the process of enchondral ossification. If these nutrients are inadequate, imbalanced, or oversupplemented, skeletal development in young growing dogs can be disturbed, leading tot severe pathologic changes. Energy requirements decrease gradually during the first year of life and unrestricted feeding can easily lead to pups being overweight. The protein requirements are strongly influenced by the quality and digestibility of protein sources in the food. In dog foods 12-14 g protein/1000 kJ appears to be adequate for growth. It is likely that the two most commonly made mistakes in dog nutrition in the Netherlands, are oversupplementation with energy and/or calcium. Restricted feeding is advised during growth and no food-additives are required when commercially prepared complete dog foods are used. PMID- 1858096 TI - [Peritonitis as complication of cysto-uretero-pyelonephritis in a cow]. AB - A Holstein-Friesian heifer had shown a haemorrhagic discharge from the vulva since three days. The animal had delivered a calf nine months previously and was seven months pregnant. On admission, haemorrhagic fluid was obtained by catheterisation from the urinary bladder and by paracentesis from the abdominal cavity. At autopsy, bilateral cysto-uretero-pyelonephritis, associated with peritonitis, was observed. A perforation of one of the lobules of the right kidney was believed to be the cause of the peritonitis. The vesicoureteral reflux might have been enhanced by the presence of polyps in the urinary bladder. PMID- 1858097 TI - [Milk fever]. PMID- 1858098 TI - [Shipping of urine samples for bacteriological studies]. PMID- 1858099 TI - The changing elderly market. PMID- 1858100 TI - The nursing home industry: past, present, and future. PMID- 1858101 TI - Financing retirement communities: the changing picture. PMID- 1858102 TI - Hospital-affiliated home health care programs: successful responses to unique environments. PMID- 1858103 TI - Patterns of contraceptive use in the United States: the importance of religious factors. AB - Previous research has shown that the major religious communities in the US have all shifted their expected family size downward but significant differences in contraceptive use styles continue to characterize Catholics, Protestants, Jews, and those of no religious affiliation. This paper examines data from Cycle IV of the National Survey of Family Growth (1988) to extend the time period covered by previous research by comparing the emerging contraceptive use patterns and fertility expectations among women in the late 1980s with earlier cohorts from previous national studies, beginning in the 1960s. The categories of religious affiliation are extended to include specific religious denominations (fundamentalist Protestants, Baptists, and other denominations, as well as Mormons) and include measures of religiosity--church attendance, the extent of receiving communion among Catholics, and attendance at church-related schools. These data are examined for blacks, Hispanics, and non-Hispanic whites. The analysis suggests how religious affiliation and religiosity continue to be important factors in the contraceptive paths to low fertility under general conditions of controlled fertility and in the context of secularization. PMID- 1858104 TI - Family planning in rural Uganda: knowledge and use of modern and traditional methods in Ankole. AB - Ankole has recorded the highest fertility in Uganda over the past several decades. One of the main proximate determinants of fertility in the area is the low level of contraception. A study of knowledge and use of modern and traditional contraceptive methods is reported in this paper. It is shown that higher proportions of women known and practice traditional methods compared with modern ones. Several factors contributing to past low use of modern contraceptives in the area are examined and current contraceptive use is also examined. PMID- 1858105 TI - Togo 1988: results from the Demographic and Health Survey. PMID- 1858106 TI - Sexual networking in the Ekiti district of Nigeria. AB - The confirmation of a significant number of HIV-positive persons and some deaths due to AIDS in Nigeria has rendered more urgent the study of sexual networking, both for an understanding of the risk of HIV transmission and also that of sexually transmitted diseases, which may serve as a vehicle for HIV infection. This article reports on a research project that concentrated initially on developing both small-scale survey and anthropological methodology to a point where reliable information was obtained. The research was carried out in both urban and rural areas of Ekiti, Nigeria, a Yoruba district 150 miles northeast of Lagos. Findings are reported from both the survey of 200 men and 200 women and the supplementary specialized in-depth studies. A high level of premarital and extramarital sexual activity was shown to exist, with higher levels among men than women and in urban than rural areas. Most female extramarital relations in rural areas were occasioned by the need for material or economic assistance and were highest among the younger wives in polygynous marriages. Male extramarital relations were highest in monogamous marriages and were frequently explained by wives' periods of postpartum sexual abstinence. Polygyny and postpartum sexual abstinence were underlying social institutions that explained much of the sexual networking. Reported levels of sexually transmitted disease were high, as were beliefs that these disease could be treated successfully by traditional healers. PMID- 1858107 TI - Sex, contraception, and pregnancy among adolescent in Mexico City. AB - This article presents the development and results of a study that analyzed the psychosocial determinants of abstaining from sexual intercourse, practicing contraception, and avoiding pregnancy. It was carried out with a representative household and a clinic sample of 12-19-year-old females of lower-middle and lower socioeconomic levels in Mexico City. Among the implications of the results for program design are: (1) the need for clarifying erroneous beliefs and providing detailed, practical knowledge concerning sexuality, pregnancy, use of and access to contraceptives; (2) a broad definition of sex education that emphasizes family communication, values clarification, provision of alternative role options for women other than motherhood, and both the goals and the skills needed to achieve them--for example, independent decision-making. Attention to male attitudes and communication skills as well as ways of improving communication and support networks among peers was also found to be essential. PMID- 1858108 TI - [The use of an optical polarization method in studying the stress deformation state of bone]. AB - Use of polarizable optical method (photoelasticity) in investigation of stress deformity state of the bone is suggested. It enables modelling the magnitude and direction of external mechanical forces acting in the bone. The resulting data are registered visually and fixed by photographic method. PMID- 1858110 TI - [The characteristics of the lung structures in the freezing of the corpse]. PMID- 1858109 TI - [The diagnosis of intravital and postmortem ecchymoses in histological sections by x-ray and luminescence study methods]. PMID- 1858111 TI - [The histo- and ultrastructural characteristics of the bone tissue in osteogenesis imperfecta]. AB - Histo- and ultrastructure of bone tissue in 28 persons (2 section observations and 26 cases of bone biopsy analysis) with congenital fragility of the bones and dysosteogenesis were studied. Age of the victims ranged from 6 months to 38 years (20 men and 8 women). Against the background of bone rarefaction and decrease in quality of basic bone substance the quantity of osteocytes for a unit of osseous beam area increases. Electron-microscopic investigation revealed changes in osteoblast structure (3 types detected) by the degree of development of granular endoplasmic reticulum. In the 2nd and 3d type of osteoblasts the decrease in the quantity of elements of granular endoplasmic reticulum was noted which may be connected with disturbance of biosynthetic processes in cell and fibrillogenesis with maturation of collagenous fibrils and their mineralization. Histo- and ultrastructure of the bone in dysosteogenesis are rather typical and in total with clinico-roentgenological data are informative enough for making diagnosis. PMID- 1858112 TI - [The terminology of self-injuries, mutilation and autoaggression]. PMID- 1858113 TI - [Thyroglobulin and myoglobin as subjects for serological investigation for expert testimony purposes]. PMID- 1858114 TI - [The simultaneous establishment of the presence and classification of human (primate), bird and fish blood by electrophoresis]. AB - Electrophoretic method of simultaneous determination of blood presence and its human (primates), bird and fish origin was developed. Method is based on detection of diagnostical characteristics possessing specific electrophoretic mobility and doesn't require use of precipitating sera. Diagnostical feature of human (primates) blood is methaemalbumin detectable in anodic part of electrophoregram and not detectable within the given test conditions in bloodstains of other animals. In bird and fish blood haemoglobin is determined in cathodic part of electrophoregram which differs from mammals blood by its electrophoretic mobility. PMID- 1858115 TI - [Patterns in the destruction of the ribs]. AB - The article deals with study of some patterns of long spongy rib bone destruction in static and dynamic load of thorax. Model of bone destruction is suggested. Multiple microfissures preceding formation of complete bone destruction were detected in border areas with fracture. They have peculiar mosaic depending on load conditions. Microfissure localization in relation to osteon structure of rib cortical lamina was stated. The results of investigations may have theoretical and applied value both in medicolegal and clinical traumatology. PMID- 1858116 TI - [The use of genomic "dactyloscopy" for the diagnosis of monozygotic twins]. AB - Possibilities of gene identification expertise for the solution of problem on mono- or dizygotic origin of twins were demonstrated. It was shown that DNA printing method makes it possible to differentiate mono- and dizygotic twins in complicated cases. PMID- 1858117 TI - [A chemical-toxicological analysis of combined poisonings by psychotropic preparations with a tricyclic structure]. AB - Conditions for chromatographic separation of melipramine with aminazine and melipramine with amitriptyline mixtures were stated. Method of chemical toxicological analysis in combined poisonings with psychotropic agents of tricyclic structure (melipramine in combinations with amitriptyline and aminazine) was suggested. Method was tested experimentally using animals. PMID- 1858118 TI - [The use of different physicochemical analysis methods for proving combined poisoning by aminazine, tizertsin and amitriptyline]. PMID- 1858119 TI - [The detection of amizil in studying different objects]. AB - Amisyl possesses toxic effect and it may become an object of forensic chemical laboratory analysis. Reactions of staining with reagents Marki, Frede and sulphuric acid as well as with reagent Dragendorf-orange residue--were used for amisyl identification. Method of amisyl detection in sorbent thin layer and identification by maximum light absorption in 258 nm area was also suggested. Usefulness of methods developed for amisyl analysis during investigation of pharmacological substances and human urine was studied. PMID- 1858120 TI - [A method for determining molybdenum in cadaveric material by using alkylphenylcyclohexylcarboxylic acid]. AB - Alkylphenylcyclohexylcarboxylic acid was found to be an efficient extractant to extract molybdenum from the cadaveric material. Method suggested is simple enough for use and doesn't require considerable amounts of chemical reagents. PMID- 1858121 TI - [The clinical picture and forensic psychiatric evaluation of psychogenic states in minor victims]. AB - Two groups of adolescent victims of sexual assault were studied, conformities of psychogenic state occurrence were analysed, age characteristics of their clinical course and dynamics were studied. Problems of forensic psychiatric evaluation of mental state of adolescent victims at different stages of judicially significant situation were developed. PMID- 1858122 TI - [Biochemical research on monoamine oxidases and their significance in the diagnosis of alcoholic intoxication]. PMID- 1858123 TI - [Erdheim's disease as a cause of sudden death at a young age]. PMID- 1858124 TI - [Fatal transcutaneous resorption of Lysol]. PMID- 1858125 TI - [I. V. Buial'skii and forensic medicine (on the 200th anniversary of his birth)]. PMID- 1858126 TI - [The signs of death from submersion in water]. PMID- 1858127 TI - [The characteristics of injuries to the ribs in children by repeated impact with solid blunt objects]. AB - Mechanisms of occurrence of thoracic lesions as well as characteristic features of repeated rib trauma in children with repeated blunt trauma were studied. Experimental data were compared with expert observations. It was stated that morphological features of repeated rib trauma in children are localized within the limits of substantia compacta or its superficial layers. There is also possibility for straightening primary incomplete fracture in repeated exposure and for forming secondary fracture, which depends on the type of force applied, its application area and direction of force action. PMID- 1858128 TI - Herpes viruses: human transducing viruses. PMID- 1858129 TI - Tracing origins with molecular sequences: metazoan and eukaryotic beginnings. AB - Milestones in the evolution of the eukaryotic cell are being discovered through the analysis of molecular sequences. As sequence data become increasingly plentiful, our ability to reconstruct the most distant evolutionary branchings of evolutionary trees is limited only by the mathematics of phylogenetic reconstruction. Analysis of ribosomal RNAs agrees with traditional analyses of morphological and developmental characters that all multicellular animals probably arose from a common ancestor, but highlights one of the major limitations of the various mathematical algorithms used. Refined methods of sequence analysis also suggest a previously unsuspected sister relationship between the eukaryotic nucleus and eocytes, a group of extremely thermophilic, sulfur-metabolizing bacteria, that questions the classical eukaryote/prokaryote division. PMID- 1858130 TI - Analysis of biochemical data by nonlinear regression: is it a waste of time? PMID- 1858131 TI - Frank Allison Linville's R.H. Wright award. PMID- 1858132 TI - Pfizer awards 1990. PMID- 1858134 TI - News from the nucleolus: rRNA gene expression. AB - Although the typical, actively growing eukaryotic cell contains over 10,000 different transcripts, half of its RNA synthetic capacity is devoted to the production of a single kind of RNA. This is the pre-ribosomal RNA, which is synthesized in a special compartment of the nucleus, the nucleolus, and is the exclusive product of transcription by RNA polymerase I. In vivo and in vitro approaches have revealed the major features of rRNA gene transcription and of the subsequent processing of the primary transcript. PMID- 1858133 TI - Calcium binding induces conformational changes in muscle regulatory proteins. AB - Calcium binding to proteins containing the 'EF-hand' structural motif regulates a variety of biochemical processes including muscle contraction. Techniques such as protein crystallography, site-directed mutagenesis and domain transplantation experiments are being used to unravel the conformational changes induced by calcium binding. PMID- 1858135 TI - Neonatal tolerance of H-2 alloantigens. Procuring graft acceptance the "old fashioned" way. PMID- 1858136 TI - The influence of the cyclosporine vehicle, cremophor EL, on renal microvascular blood flow in the rat. AB - Cyclosporine nephrotoxicity may be due to glomerular hypoperfusion. Previous experimental and clinical studies have demonstrated a decrease in renal blood flow and an increase in renal vascular resistance. Cremophor EL, which is the vehicle in which CsA is dissolved, is thought to be a factor involved in intrarenal arteriolar vasoconstriction. To determine the relative contributions of the vehicle and CsA to intrarenal arteriolar vasoconstriction, we used in vivo videomicroscopy and Doppler velocimetry to measure changes in renal microvascular blood flow in the rat. A 5-min intravenous infusion of 20 mg/kg of CsA resulted in a 17% mean reduction (P less than 0.05) in the diameter of preglomerular interlobular arterioles and an associated 60% reduction (P less than 0.05) in microvascular blood flow by 15 min. Cremophor EL/ethanol equivalent caused less vasoconstriction (up to 10%) but resulted in a 42% mean decrease (P less than 0.05) in microvascular blood flow, probably secondary to a 38% mean decrease (P less than 0.05) in cardiac output and 13% decrease in arterial pressure. We conclude that cremophor EL does contribute to in vivo reduction of preglomerular microvascular blood flow in the rat. This may be particularly important when using this intravenous preparation in the study of CsA nephrotoxicity. PMID- 1858137 TI - Total pancreatectomy in the pig for islet transplantation. Technical alternatives. AB - Pigs appear to be a suitable biological and logistical animal donor of islets for xenotransplantation in human diabetic type I recipients. To improve the islet isolation technique in this species, to evaluate the islet function in vivo, and to assess the toxic effects of various immunosuppressive regiments on transplanted islets will necessitate a model of the pancreatectomized pig suitable for islet autotransplantation. We describe three techniques of total pancreatectomy in pigs. The first removed the pancreas in order to study postoperative management and pig survival; no attempt was made to preserve the pancreas for islet isolation. The second consisted of a pancreatectomy in a surviving pig, with careful preservation of the whole pancreas for subsequent islet isolation. The third was rapid en bloc procurement of the pancreas and duodenum, to obtain a pancreas solely for the purpose of islet isolation. We conclude that pigs tolerate and survive a total pancreatectomy--they are suitable animals for islet isolation and possible autotransplantation. The result of islet isolation does not appear related to the pancreas procurement technique; however, the islet yield must be improved before autotransplantation can be functionally successful. PMID- 1858138 TI - Cluster-function relationship of rat-antimouse P55 IL-2 receptor monoclonal antibodies. In vitro studies of the CTL-L2 mouse cell line and in vivo studies in a delayed-type hypersensitivity model in mice. AB - Monoclonal antibodies directed against the P55 component of the interleukin 2 receptor (IL-2-R) have been used to prevent allograft rejection in various animal models, including primates and man. This study compares the functional effects of seven MoAbs directed against the mouse IL-2-R P55 chain both in vitro using the mouse CTL-L2 cell line and in vivo in a sheep red blood cell-induced delayed-type hypersensitivity model. Data from in vitro studies showed that a cluster of four MoAbs (cluster I: 5A2, 125, 135 [IgG2a] and AMT13 [IgG2b]) competed with IL-2 for binding to the P55 chain and caused an inhibition of IL-2-induced proliferation on CTL-L2. The respective dissociation constants (Kd) of the four MoAbs were 1.1, 1.4, 2.5, and 5.5 nM, and they all displayed a common maximal binding capacity of 2 x 10(5) sites per cell on CTL-L2. None of these MoAbs were found to fix rabbit complement. The three other MoAbs (2E4: IgG2a, 7D4: IgM, PC61: IgG1) with respective Kd of 0.8, 0.2, and 0.85 nM and maximal binding capacities of 2 x 10(5), 4 x 10(5) sites per cell did not interfere with IL-2 binding and did not affect the IL-2-induced proliferation of the murine cell line. All three MoAbs were found to define three separate epitopic clusters independent of cluster I. Among them, only 2E4 induced a strong complement-mediated cytotoxicity. In vivo experiments showed that all MoAbs from cluster I were efficient in suppressing the DTH reaction and that the magnitude of their effect was consistent with their respective Kds. At a suboptimal dose of 1 microgram per day, the DTH inhibition indices were 40%, 43%, 23%, and 9% for 5A2, 125, 135, and AMT13, respectively. The 2E4 MoAb was found to be as efficient as cluster I MoAbs in suppressing DTH (53% inhibition at 1 microgram/day) while 7D4 and PC61 induced only a moderate inhibitory effect (37% inhibition for each MoAb given at 10 micrograms/day, compared with 70% inhibition for cluster I MoAbs). Taken together, our results indicate that blocking the IL-2/IL-2-R interaction without complement fixation is sufficient per se to attenuate the DTH reaction, and conversely that strong complement-mediated cytotoxicity in the absence of a functional effect in the IL 2/IL-2-R interaction is also effective in this system. Finally, no synergistic effect between MoAbs belonging to different clusters was evidenced in the DTH model. PMID- 1858139 TI - The host/donor origin of cells mediating NK and NK-like cytotoxic activity in F1 hybrid mice with acute graft-versus-host reactions. PMID- 1858140 TI - Simultaneous orthotopic liver and heterotopic pancreas transplantation. PMID- 1858141 TI - Encephalopathy associated with OKT3 administration. Possible interaction with indomethacin. PMID- 1858142 TI - Induction of long-term survival of hamster heart xenografts in rats. AB - The aim of this study was to determine the mechanisms responsible for concordant xenograft rejection using the hamster-to-rat heart graft model. Even though it was known that rat CD4 positive T cells proliferated to hamster stimulators in mixed lymphocyte reactions, the depletion of CD4 positive T cells in rat recipients did not lead to an extension of xenograft survival. Suppression of T cell immunity using other monoclonal antibodies or cyclosporine also failed to improve survival. Only by depleting complement with cobra-venom factor could hamster xenograft survival be prolonged, and long-term survival was achieved by combining CsA with COF. High-antibody titers to hamster cells were found after transplantation of hamster hearts, and evidence is presented that rejection of these "concordant" xenografts is mediated primarily by antibody-complement mechanisms. The antihamster antibodies were produced in the absence of T cell help, which suggests that antibody-mediated graft destruction cannot be inhibited by suppression or depletion of T cells. Pharmacologic depletion of complement for the clinical application of concordant xenografts is a promising avenue of future research. PMID- 1858144 TI - New devices for harvesting a hepatic graft from a living donor. PMID- 1858143 TI - Esophageal complications in orthotopic liver transplant patients. PMID- 1858145 TI - Intrahepatic portocaval shunt for variceal hemorrhage prior to liver transplantation. PMID- 1858146 TI - Increased urinary excretion of endothelin-1 and its precursor, Big-endothelin-1, in rats chronically treated with cyclosporine. PMID- 1858147 TI - Donor essential fatty acid deficiency does not prolong heterotopic cardiac allograft survival in rats. PMID- 1858148 TI - Survival of cardiac xenografts in rhesus monkeys. PMID- 1858149 TI - Soluble interleukin-2 receptor in heart transplant recipients. PMID- 1858150 TI - Attenuation of ischemia-reperfusion injury of the liver in dogs by cyclosporine. A comparative study with allopurinol and methylprednisolone. AB - The effects of pretreatment with cyclosporine, allopurinol, or methylprednisolone on ischemia-reperfusion injury of the liver were investigated. A total of 32 adult mongrel dogs that received one of the pretreatments were divided into four groups and were subjected to 90 min liver ischemia. Serum activities of aspartate aminotransferase (s-AST) and lactate dehydrogenase, (s-LDH) as well as animal survivals were used as indicators of liver injury. The elevation of both s-AST and s-LDH was significantly suppressed by pretreatment with cyclosporine as much as by allopurinol. However a significant improvement in animal survival was obtained only in the cyclosporine-pretreated group. Pretreatment with methylprednisolone did not affect either the activities of s-AST and s-LDH or animal survivals when compared with the control group. These data suggest that cyclosporine is a potent protector against ischemic liver injury--as effective as allopurinol or methylprednisolone. Although the precise mechanism of the effect of cyclosporine on liver ischemia still remains unknown, these observations may be of use in liver transplantation. PMID- 1858151 TI - The function of a colloid in liver cold-storage preservation. AB - The value of colloid in preservation of the liver by cold storage has not yet been fully clarified. Therefore, we studied the effects of colloid on cell swelling, liver weight, and bile production after cold storage in rat liver tissue slices and isolated rabbit liver. In rat liver tissue slices cold-stored for 24 hr in UW solution, total tissue water (TTW) was the same as in the control freshly unpreserved tissue and omitting the colloid (hydroxyethyl starch) from the UW solution did not affect the TTW. However, after cold storage for 24 hr in Perfadex, TTW was markedly increased (by 100%, P less than 0.001). Omitting the colloid in this solution, dextran, or replacing it with hydroxyethyl starch, did not affect this increase in TTW. Thus, the hypothermia-induced cell swelling evident after preservation in Perfadex was not prevented by colloid. Rabbit liver cold-stored in UW solution for 24 hr lost 15.4 +/- 4.7% of weight, but omitting the colloid from UW solution decreased this weight loss to 3.1 +/- 3% (P less than 0.01). In contrast, rabbit livers cold-preserved in colloid-free Perfadex gained 23.3 +/- 5.7% in weight. Adding colloid, either dextran or hydroxyethyl starch, decreased significantly this weight gain, to 9 +/- 3.7% and 10.4 +/- 1.8%, respectively (P less than 0.01), probably as a result of colloid osmotic pressure, preventing the interstitial edema. Rabbit livers preserved for 24 hr in UW solution, with or without colloid, produced the same amount of bile as control unpreserved livers. In contrast, livers preserved in colloid-free Perfadex for 24 hr had a markedly impaired bile production (3.9 +/- 0.9 ml/100 g) as compared with control livers (15.5 +/- 2.6 ml/100 g, P less than 0.01). Colloid partially restored this impaired bile production, to 8 +/- 1.4 mg/100 g by dextran and to 8.5 +/- 1.7 ml/100 g by hydroxyethyl starch, respectively (P less than 0.01). Thus, although colloids do not prevent the hypothermia-induced cell swelling, they prevent the development of interstitial edema, and, hence, improve the liver function. PMID- 1858152 TI - Medicine and ethics. How to allocate transplantable organs. AB - Organ transplantation has made tremendous strides in the last decade. The demand for transplantable organs has far outstripped the supply; waiting lists have grown long and patients are dying for want of vital organs. Therefore policies and criteria that guide the allocation of transplantable organs become ever more important. Over the years, allocation policies have evolved by including both medical and ethical considerations, and much work has gone into defining and analyzing components of such policies. However, they have often grown by accretion, and a parallel analysis of both sets of approaches did not occur. This article attempts to integrate medical and ethical considerations, and to develop a schema that will permit review, redefinition, and--it is hoped--development of a fairer, more equitable and responsive allocation system. PMID- 1858153 TI - Long-term quality of life after kidney transplantation in childhood. AB - Transplantation is the treatment of choice for children with end-stage renal disease. However, the long-term quality of life and socioprofessional outcome for those with successful transplants have not previously been reported. We studied these factors in patients transplanted when less than 18 years old who currently have greater than or equal to 10 years of graft function. A total of 57 questionnaires were sent out; 57 (100%) responded [24 female and 33 male patients; average (+/- SD) age at tx = 10 +/- 5 years (0.9-17.7); average f/u = 15.6 +/- 3 years (10-26); current age = 26 +/- 5 years (12-38); 26 had greater than 1 transplant]. Of the 57 respondents, 9 are less than 18 (all are in school); 48 are greater than or equal to 18 (7 in school, 37 employed, 4 unemployed); 12 are married, 1 engaged, and 2 divorced; and 9 have children. While in school, 43 (75%) had participated in sports, 37 (65%) in other extracurricular activities; 7 (12%) were A and 33 (58%) B students; 15 (26%) received awards or scholarships. For those working, the range of occupations is broad (average work week = 41 +/- 5 hr). Health-related absence from work has been nonexistent for 93%. Health is rated as good to excellent by 91% and fair by 9%. The future is regarded as hopeful or promising by 80%. Similarly, 89% are satisfied with life in general; 95% said health never or seldom interferes with family life; 95% feel health and drug side effects are of no or minor concern in sexual relationships. Only 3% feel health is a problem in maintaining a sexual relationship (41% are not sexually active). Only 4% stated that health often interferes with social life; 98% meet with friends on a regular basis; 76% are satisfied with personal relationships and 8% dissatisfied; 91% are satisfied with their ability to perform at work or school and 5% dissatisfied. Of note, 32% are dissatisfied with body appearance. Major concerns are short stature and brittle bones. Major suggestions include education/support groups to deal with teasing at school and peer problems. We conclude that transplanted children with long-term graft function have a favorable social and professional outcome. Overall, quality of life seems excellent. PMID- 1858154 TI - A randomized prospective trial comparing cyclosporine monotherapy with triple drug therapy in renal transplantation. AB - In a prospective trial 151 recipients of renal transplants were randomly assigned to treatment with CsA alone (74 patients) and to low dose of AZA, prednisolone, and CsA (77 patients). At two years, graft survival was 84% for the monotherapy and 90% for the triple therapy. This difference was not statistically significant. The number of rejection episodes was similar in the two groups, but the severity of rejection was significantly worse among the patients on monotherapy. More kidneys were lost because of rejection (6 versus 3), and a higher number of methylprednisolone pulses was used for treating rejection (5.2 +/- 2.3 versus 4.3 +/- 2.9; P = 0.0077). CsA nephrotoxicity episodes were more frequent among patients on monotherapy (23 versus 7; P less than 0.02). Infectious episodes were equally distributed between the two groups. Creatinine clearance was poorer in the monotherapy-treated patients at the third month (42 +/- 16 ml/min versus 48 +/- 15 ml/min; P = 0.02), but no differences were observed between the two groups since the sixth month after transplantation. Many patients on monotherapy required changes in maintenance therapy. In fact, one patient was switched to conventional immunosuppression because of Cremophor induced anaphylaxis. Another patient who developed Kaposi's sarcoma 4 months after surgery was switched to steroids alone. Excluding 5 patients who lost their grafts a few days after transplantation, only 30 of 74 patients (40%) could be kept without steroids. We conclude that both the therapeutic protocols can give good results in renal allotransplantation; however, monotherapy could create some problems in keeping the balance between drug toxicity and significant immunosuppression. On the contrary, triple therapy is easier to handle, especially in the early posttransplant period when the differential diagnosis between acute rejection and CsA-related nephrotoxicity can be difficult even for a skilled clinician. PMID- 1858155 TI - Posttransplant neopterin excretion in renal allograft recipients--a reliable diagnostic aid for acute rejection and a predictive marker of long-term graft survival. AB - During the immediate posttransplant period, daily measurements of urinary neopterin, which is produced by stimulated macrophages, were evaluated in 294 consecutive recipients of renal allografts for their diagnostic value in acute graft rejection. The ability of mean and peak neopterin excretion values to predict long-term graft survival was analyzed on the basis of an eight-year follow-up. Immunosuppressive therapy (cyclosporine +/- prednisone versus azathioprine + prednisone) and initial nonfunction did not influence neopterin excretion. In patients with rejection episodes and in those with infections, neopterin levels were significantly increased. Diagnostic sensitivity and specificity with regard to rejection diagnosis were assessed for different levels of neopterin. By statistical analysis, a significant association between increased neopterin and higher risk of rejection was found, which was particularly pronounced in patients receiving cyclosporine. Increase in neopterin excretion preceded clinical rejection diagnosis by up to four days. Peak neopterin values above 800 mumols/mol urinary creatinine observed during the posttransplant period, were associated with significantly poorer graft survival. A multivariate analysis showed that peak neopterin levels, age of patients, and early posttransplant presence/absence of acute rejection were significant and independent joint predictors for long-term graft survival. Measurement of neopterin can be of help as an additional marker in early diagnosis of renal allograft rejection, and high neopterin values during the initial posttransplant period are associated with poorer long-term graft survival. PMID- 1858156 TI - Renal handling of urate and the incidence of gouty arthritis during cyclosporine and diuretic use. AB - The incidence of gouty arthritis and the role of renal urate handling and diuretic use were studied in 85 cadaveric kidney graft recipients with a graft functioning for at least two years. The incidence of gout was 24% in patients using cyclosporine (CsA, n = 55); no patient using azathioprine (Aza, n = 23) had gout. In patients using CsA, the fractional urate clearance decreased between 1 and 3 months after transplantation, thereafter remaining stable at a significantly lower level than in patients using Aza, pointing toward a specific effect of CsA on tubular urate handling. This impaired fractional urate clearance was not reversible up to 18 months in 7 patients after conversion from CsA to Aza, suggesting irreversible tubular damage. Multiregression analysis showed that the impaired fractional urate clearance and the use of furosemide were significant contributors to the occurrence of gout in patients using CsA. PMID- 1858158 TI - Cardiac transplantation in patients with preexisting malignancies. AB - A history of preexisting malignancy has been considered a contraindication to cardiac transplantation. The reasons for this prejudice include concerns about potentially deficient intrinsic immunomodulation and fear of cancer recurrence (or development of second cancers) because of therapeutic immunosuppression. In the past four years at the Northern Indiana Heart Institute seven patients with preexisting malignancies underwent cardiac transplantation. Their two-year survival rate was 100%, which is comparable to a rate of 81% in non-malignancy patients. After an average 31 months of follow-up (range = 6-56 months), only one patient has had a recurrent tumor (basal cell carcinoma). Statistical comparison of immunosuppression dosages, incidences of rejection, and incidences of infections between patients with preexisting malignancy and those without preexisting malignancy was performed. We found that the only significant difference was an increased number of infections in preexisting malignancy patients. Additionally, we found no difference in the incidence of posttransplant coronary artery disease in the preexisting malignancy group when compared with those patients without preexisting malignancies. This study demonstrates that patients who have been successfully treated for malignancies have no greater incidence of rejection than those patients without preexisting malignancy. Furthermore, preexisting malignancy patients require no significant modulation of immunosuppression. Although preexisting malignancy patients have a higher incidence of infections than patients without preexisting malignancy, their two year survival is not worse than the patients without preexisting malignancy. PMID- 1858157 TI - Dynamics of soluble interleukin-2 receptor levels immediately after heart transplantation. Attenuation of increase by OKT3 therapy. AB - Quantification of T cell activation after cardiac transplant by measuring serum soluble interleukin 2 receptor levels daily may give insight into immunologic dynamics after cardiac allograft implantation. It was our hypothesis that this protein would demonstrate a characteristic rise after heart transplant not related to severe rejection that was distinct from a control group, and that this increase could be attenuated with OKT3 therapy. We measured soluble interleukin 2 receptor levels daily for two weeks in 26 patients undergoing orthotopic cardiac transplantation (19 receiving triple therapy immunosuppression with cyclosporine, azathioprine, and prednisone, and 7 with OKT3 added days 1 through 5). Interleukin-2 receptor levels for transplant patients were compared with 15 control subjects (14 undergoing bypass surgery and one valve replacement). Mean soluble interleukin-2 receptor level for the entire two-week period was higher for transplants versus controls; 839 +/- 31 U/ml vs. 504 +/- 20 U/ml (mean +/- SEM; P less than .05). Patients receiving OKT3 had a lower level (670 +/- 39 U/ml) than those not (902 +/- 36 U/ml, P less than .05) despite the fact that mean biopsy scores for the observation period were not significantly different. No significant rejection or infection episodes occurred in any patient. These results describe, for the first time, sequential changes in soluble interleukin 2 receptor levels early after heart transplant and demonstrate that the characteristic early rise can be attenuated with short-term OKT3 administration. PMID- 1858160 TI - The long-term outcome of OKT3 compared with cyclosporine prophylaxis after liver transplantation. AB - We report the long-term follow-up (greater than 1 year) of 46 patients (12 pediatric) randomized to receive OKT3 for the first 14 days after OLT with low dose steroids compared with 39 patients (8 pediatric) who received cyclosporine, steroids, and azathioprine. The mean period of follow-up for survivors was 648 +/ 261 days for the OKT3 group and 682 +/- 216 days for the cyclosporine group. Of the OKT3 patients, 46% were rejection-free in the first month compared with 31% of CsA-treated patients (P = NS). Rejection occurred after 1 month in 21% of the OKT3 group patients compared with 19% of the CsA group patients. One patient in each group developed vanishing bile duct syndrome. Eight patients in the OKT3 group and 13 in the CsA group experienced steroid-resistant rejection and required OKT3 rescue. In the 8 patients in whom OKT3 was reused, 4 had a positive ELISA after prophylaxis, and in 6, CD3-positive cells were greater than 10% during OKT3 reuse. Five patients resolved the episode. Of patients receiving OKT3 prophylaxis, 39% developed anti-OKT3 antibodies. In the OKT3 group 83% of patients and in the CsA group 75% currently have normal liver function. There was no difference in serum creatinine for either adult or pediatric recipients at 12 months in the two groups. Eight episodes (2 CMV) of severe infection occurred after 1 month in the OKT3 group compared to 11 (4 CMV) in the CsA group. Graft survival, 63% for the OKT3 group and 73% for the CsA group, and patient survival, 67% for the OKT3 group and 84% for the CsA group, were not significantly different in the two groups. We recommend reserving the use of OKT3 for resistant rejection or when cyclosporine is contraindicated, as we can show no long-term benefit from its routine prophylactic use. PMID- 1858161 TI - The lack of memory B cells in immune bone marrow. AB - Adoptive transfers of lymphoid populations between Ig-congenic strains of mice were performed to evaluate the presence of memory cells in the bone marrow of immune animals. Transfer of immune splenic B cells or immune peripheral blood mononuclear cells effectively transferred antigen-specific IgG1 antibody responses of donor origin. In contrast, BM from immune animals did not transfer a memory response. The lack of memory transfer with immune BM was not due to a suppressive activity of BM since (1) Purified antigen-specific B cells from BM did not transfer memory while purified antigen-specific B cells from immune spleen was a potent source of memory cells, and (2) cotransfer of immune BM with a source of memory B cells (immune PB) did not suppress the transfer of memory. Although immune BM did not have cells capable of transferring antigen-specific memory, copious amounts of antigen-specific antibody were spontaneously produced by immune BM in vitro. These studies suggest that the transfer of immunological memory observed in human BM transplant cases may be the consequence of PB contamination of BM preparations when collected. PMID- 1858159 TI - Long-term metabolic and quality of life results with pancreatic/renal transplantation in insulin-dependent diabetes mellitus. AB - Evaluation of whole-organ pancreas transplantation in the therapy of IDDM has been difficult because of generally poor graft survival and significant complications in past experience. We report a technically successful simultaneous pancreas/kidney transplant program with patient and graft survival of 85% over 3 years of follow-up (mean 21 months) in 33 subjects with IDDM. Glucose metabolism was normalized without need for exogenous insulin immediately posttransplant in all but one recipient and remained normal in 85% of recipients. The outcome in pancreas/kidney recipients was compared with that in 18 insulin-dependent diabetic recipients of kidney transplant only performed in the same period. Quality of life was assessed with one general and one diabetes-specific questionnaire. General quality of life issues improved significantly in both pancreas/kidney and kidney recipients, but diabetes specific quality of life improved only in the pancreas/kidney recipients. Pancreas/kidney recipients required twice as long a period of hospitalization for the transplant and two times as many readmissions for a variety of complications. Only a minority of hospital admissions was strictly attributable to the pancreas graft. Of the five deaths in the pancreas/kidney recipients, two were attributable to the pancreas transplant. Pancreas transplantation in IDDM can now be accomplished with a high degree of success, resulting in normalized glucose metabolism and with overall mortality similar to kidney transplantation alone. Successful pancreas transplantation improves quality of life with respect to diabetes but this benefit is accomplished at a cost of increased hospital admissions and complications related to the transplanted pancreas. The effects of pancreas transplantation on the long-term complications of insulin-dependent diabetes remain unknown. PMID- 1858162 TI - Effect of dry season supplementation of Sanga cattle in Zambia. AB - Supplementation of lactating Sanga cows in central Zambia with low cost crop residues and urea-mineral licks resulted in significant increases in milk offtake (79%), total daily milk (86%), and daily liveweight gain of their calves (86%). At 1988 market prices the value of the additional milk (ZK54.00) and of liveweight of both cow and calf (ZK189.00) over the 13 weeks exceeded the estimated costs of inputs by ZK180.00. PMID- 1858163 TI - Influence of partial suckling of crossbred dairy cows on milk offtake and calf growth in the Ethiopian highlands. AB - The effects of implementing a restricted suckling regime with crossbred dairy cows have been examined in the Ethiopian highlands. Calves were allowed to suckle their dams for two minutes before each milking until weaning and this system was compared with the common practice of rearing by bucket feeding. Restricted suckling significantly increased calf growth rate to weaning, from 0.31 to 0.53 kg/d (P less than 0.01). No differences in calf growth post-weaning occurred, so that the 20 kg difference in liveweight that had been achieved by the restricted suckled calves by the time of weaning persisted until the calves were nine months old, when observations ceased. Total milk offtake was not significantly affected by treatment, although that obtained from the partially-suckled animals over their whole lactation exceeded that from the other treatment by 15%. Partial suckling delayed return to oestrus post partum but this was offset to some degree by fewer services per conception, hence calving interval was not significantly increased. Voluntary feed consumption was similarly unaffected and it is concluded that restricted suckling offers tangible advantages for adoption by smallholders using crossbred cows in dairy production systems. PMID- 1858164 TI - Breed and environmental influences on weaner lamb production in Zimbabwe. AB - Performance of the Dorper and Mutton Merino breeds and their crosses was assessed from 1,305 ewe and 1,453 lamb records from six lambing seasons. Dorper and Mutton Merino were mated in all combinations under an accelerated lambing system and crossbred females were mated to Suffolk rams. The Dorper and Mutton Merino breeds were not significantly different for fertility, pre-weaning lamb growth and survival. Suffolk sired lambs from crossbred ewes grew rapidly and were heaviest at birth and at weaning. They also survived better than lambs from the other breeding groups and this contributed to the higher weaning rate (P less than 0.05) in crossbred ewes. Weight of weaned lambs per ewe exposed to the ram per season was 12% higher (P less than 0.05) in the Dorper than the Mutton Merino ewes. However lifetime production was 28% higher (P less than 0.01) in Mutton Merino ewes due to significantly superior longevity. Crossbred ewes were highly productive. Individual heterosis was not significant but estimates were positive for most traits. Growth rate and survival of lambs increased as age of dam increased to 48 and 40 months respectively. Lambs born to previously non lactating ewes were heavier and survived better than lambs born to ewes lactating in the previous season. Lambs born and reared as singles were 25% heavier at birth (P less than 0.001) and 52% heavier at weaning (P less than 0.001) than those born and reared as twins. Male lambs grew faster and were 7% heavier at weaning than females (P less than 0.001). PMID- 1858165 TI - Comparison of sesame cake and cottonseed as supplementary sources of protein to weaned N'Dama bull calves in The Gambia. AB - The potential for increased productivity of N'Dama cattle in response to small supplementary inputs of proteinaceous by-products has been shown to be substantial under village husbandry conditions in The Gambia. Young N'Dama bulls were used to compare sesame cake with cottonseed as sources of supplementary protein during the wet and early dry seasons of 1987. They were fed 0, 40, 80 or 160 g crude protein/day in these forms for four months. Supplementation significantly increased growth rate from 169 g/d in controls to means of 272 and 271 g/d for those given sesame cake and cottonseed respectively; there were no significant differences among the supplemented groups. During the four months of the dry season immediately after supplementation ceased all previously supplemented groups grew significantly more rapidly than the controls (at least P less than 0.05), indicating a substantial carry over effect of the supplements. Over this period the mean gain of the groups previously given sesame cake exceeded that of those that had received cottonseed (217 cf. 158 g/d; P less than 0.01). The economic benefits of these responses were substantial. PMID- 1858166 TI - Retrospective observations on the transmission of East Coast fever in Zimbabwe. AB - Records of 283 outbreaks of East Coast fever in Zimbabwe in the period 1914 to 1946 reveal that transmission of infection occurred throughout the year with peaks in January to March and May to July. The high level of transmission in January to March coincides with the known seasonal occurrence of adult Rhipicephalus appendiculatus. It is suggested that transmission at other times of the year may have been effected by a population of R. appendiculatus which did not exhibit a strictly seasonal life-cycle and has since been eradicated. PMID- 1858167 TI - Effect of consumption of molasses/urea blocks on the growth of housed bullocks fed ad libitum with Pennisetum purpureum. AB - Ten bullocks in individual pens were provided ad libitum with cut chopped pasture grass (Pennisetum purpureum). One group of five animals had access to a molasses/urea block (experimental group) and the other group of five did not (control group). Daily dry matter intakes of 5.04 kg/animal (control group) and 4.83 kg/animal (experimental group) were not significantly different. However the experimental group gained weight at a significantly (P less than 0.05) faster rate (514 g/animal per day) than the control group (346 g/animal per day). Food conversion efficiency was significantly (P less than 0.01) better in the experimental group (11.6 kg feed per kg weight gained) than in the control group (16.4 kg feed per kg weight gained). Mean daily intake of the molasses urea blocks was 206 g per animal. PMID- 1858169 TI - [Meta-analysis--a pseudoscience or a useful tool?]. PMID- 1858168 TI - Comparison of the calf suckling technique and milk oxytocin test for estimation of milk yields. AB - The calf suckling technique and milk oxytocin test were compared as methods to quantify lactation yields in Sanga-type cows in the multi-purpose livestock sector of central Zambia. There was no significant difference between the overall means derived from 154 observations. The oxytocin method interferes less with the multi-purpose system of management, is less time consuming and does not require expensive calf weight scales. PMID- 1858170 TI - [Effect of salt-restriction on blood pressure. A review over epidemiological studies and a meta-analysis of clinically controlled studies]. AB - Cross-section regression analyses of some of the world's populations suggest a direct linear relationship between mean blood pressure and mean salt-intake. Since such investigations have hitherto been partly based on information about dietary salt intake, which is a questionable measure, we performed an analysis including 28 male populations and an analysis including 21 female populations solely based on 24 hour sodium urinary excretion. The regression analysis confirmed that a direct linear relationship between blood pressure and 24 hour sodium urinary excretion existed, since the blood pressure in a population was about 7 mmHg/6 mmHg higher than in a population which consumed 100 mmol less salt. We were, however, not able to correct for confounders. This was done in the recently published "Intersalt" study in which the linear relationship between median blood pressure and median salt intake disappeared after correction for weight and alcohol intake. From the regression coefficients from "Intersalt" it can be deduced that a reduction in salt intake from 150 mmol to 75 mmol may reduce blood pressure by 1.6/0.05 mmHg. Most epidemiological studies have not been able to demonstrate a correlation between salt intake and blood pressure within population. Still, on the basis of uncontrolled clinical studies it has been claimed that salt-restriction may reduce blood pressure. Consequently we also performed a meta-analysis of 15 controlled clinical trials dealing with the effect of salt-restriction on blood pressure within a population. This meta analysis including 704 patients showed that a reduction in average salt intake from 150 mmol to 75 mmol may reduce blood pressure by 2.4/1.4 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858171 TI - [Postoperative urinary retention]. AB - Postoperative retention of urine (PU) is a common complication which may occur after any surgical intervention. It may affect both sexes in all age groups and result in considerable morbidity. The frequency depends upon the type of operation and its duration but statements in the literature vary greatly on account of inaccurate and varying definitions and uncertain diagnostic criteria. Intervention in the true pelvis results in the highest frequencies of postoperative urinary retention. The method of anesthesia is of lesser significance. Spinal anesthesia and epidural morphine constitute, however, a particular risk for the development of postoperative retention of urine. The pathological physiology is complex and includes: 1) disturbance of the balance between the sympathetic/parasympathetic influence on bladder and urethral function, 2) drugs which inhibit the miction reflex, 3) anaesthesia and sedation which cloud the awareness of bladder filling, 4) rapid filling of the bladder with subsequent overdistension, 5) lesion of the nerve fibres to the lower urinary tract, 6) mechanical obstruction and 7) difficult positions and/or situations for miction. Preoperative information about difficulty in emptying the bladder constitutes a predisposing factor and may require preoperative elucidation and treatment. Postoperative retention of urine may be countered by informative and practical measures and restriction of fluid intake. In selected cases, prophylactic treatment with alpha-blockers and prostaglandin may reduce the frequency. Therapeutically, oral parasympathomimetica do not appear to be effective while alpha-blockers may be employed. In cases where catheter treatment is employed and which is anticipated to be required for more than 48 hours, suprapubic drainage is recommended as this results in fewer cases of urinary infection than transurethral indwelling catheters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858173 TI - [The patterns of admission for patients with suspected acute myocardial infarction]. AB - The patterns of admission to hospital for 161 patients with suspected acute myocardial infarction during the period 1.2.1988-30.9.1988 were investigated. This revealed that 59% called their doctor, 20% called the ambulance directly, 11% arrived at the doctor's office or casualty department and 7% were admitted with cardiac arrest. The durations of delay were investigated. The median duration of delay by the doctor was 15 minutes but only 7% of the cases were escorted to hospital by the doctor. In 53% of the cases, the doctors waited for the ambulance without escorting the patient. In 40% of the cases, the doctors did not wait for the ambulance. 44% of the patients with acute myocardial infarction referred to hospital by doctors who did not accompany them were in poor condition on arrival (one patient died in the ambulance). 33% of these patients died in hospital. The ambulances were staffed by three persons with paramedical training in only 5% of the cases when the patient first called the doctor and in 41% of the cases when the ambulance was called as an emergency. The study reveals that prehospital treatment of cardiac patients should be improved. PMID- 1858172 TI - [Autotransplantation of splenic tissue after splenectomy in adults]. AB - Splenectomy involves a risk of development of postsplenectomy sepsis, PSS. An assessment of the incidence of PSS is made on the basis of a review of the literature. Experimental studies on animals suggest that splenic autotransplantation exerts a protective effect following nasal exposure to Streptococcus pneumoniae. Where other routes of exposure are concerned, the results are contradictory, but no general effect has been found. Clinical data is limited and the effect cannot be assessed as yet. The technique of autotransplantation and the commonest complications are summarised. On this basis, several guidelines are presented. It is concluded that splenic autotransplantation is a potentially beneficial alternative to total splenectomy but that it involves a certain risk. The procedure should, therefore, only be carried out under clinically controlled conditions. PMID- 1858174 TI - [General practitioners' attitude to prescription of psychopharmaceuticals. Autonomy versus paternalism, education and understanding of disease]. AB - The object of this investigation was to illustrate the attitudes of general practitioners to prescription of psychotropic drugs and to mental illness. The qualitative research interview method was chosen as the method employed here. Fourteen general practitioners were interviewed while one did not wish to participate. A marked difference was found between the attitudes of the general practitioners to respect the autonomy of the patients or to act paternally. The paternal general practitioner could either prescribe psychotropic drugs on his own initiative or refuse prescription. General practitioners who respected autonomy were relatively restrictive in their prescribing habits so that respect for autonomy was by no means expression for free prescription of psychotropic drugs. Their goal was that the patient should be placed in a situation where he/she could choose and determine personally. The general practitioners considered that their undergraduate and postgraduate training in treating patients with mental illness was inadequate. Taking into consideration how frequently patients with conditions of this nature are seen in general practice, this must be regarded as a serious deficit in medical training. A number of general practitioners have, however, received postgraduate training in this subject. General practitioners did not consider patients who consulted them with mental conditions as mentally ill but they did not have an alternative disease model by which they could classify the problems and complaints of these patients. PMID- 1858175 TI - [Patients' attitude to long-term use of benzodiazepines. A questionnaire study]. AB - The object of this investigation was to illustrate patients understanding of the background for commencing and continuing or discontinuing, respectively, benzodiadiazepine medication with emphasis on attitudes, norms and values on which this medication is based. The quantitative research interview method was selected as the method employed here. Twenty-one patients participated. Ten of these continued medication. Nine patients had originally discontinued medication but had begun again for various reasons. Two patients had discontinued medication completely. Patients who employed benzodiazepines daily had only few trepidations about consumption of drugs while patients who only employed medication occasionally had a series of trepidations. Nevertheless, a considerable tendency to return to benzodiazepines under conditions of stress was observed. The justification for intake of benzodiazepines was frequently altered during the course of time. Considerable "medicalization" of non-medical problems was observed. The problems for which the patient was prescribed medication with benzodiazepines were frequently bio-psycho-social-extential problems. The majority of patients were, however, aware of this "medicalization". Benzodiazepines were not employed as euphoric agents. PMID- 1858176 TI - [Naproxen versus indomethacin as night-time medication for patients with rheumatoid arthritis]. AB - The investigation consisted of a double-blind cross-over study of the effect of 75 mg indometacin, 500 mg naproxen or a placebo in 63 patients with rheumatoid arthritis accompanied by night pain and morning stiffness. All the patients received day treatment with 250 mg naproxen b.i.d. Only a few patients benefitted from the treatment at night and no differences in the effect of indometacin and naproxen were observed. Naproxen was better tolerated than indometacin. Day treatment with naproxen, which has a relatively long half life time decrease the need for supplementary treatment at night. PMID- 1858177 TI - [Breast cancer in the Faeroe Islands during 1958-1987]. AB - From 1958 to 1987, a total of 269 primary breast cancers were diagnosed in 261 women living in the Faroe Islands. The five-year survival was 46.7% (95% confidence interval 40.3-53.0%) and the median survival four years and three months. The incidence of breast cancer in the Faroe Islands remained constant from 1958 to 1972 after which an increase occurred. At present, one in 20 Faroe women will develop breast cancer before the age of 75 years. The time trend in breast cancer incidence is similar in the Faroe Islands and in Denmark, but the incidence is significantly lower in the Faroe Islands at a level corresponding to 2/3 of the Danish. This difference is presumed to be due to a different prevalence of risk factors for development breast cancer. PMID- 1858178 TI - [Arthroscopic synovial resection of the talocrural joint]. AB - Arthroscopic resection of the synovial membrane was employed in the treatment of chronic pain antero-laterally in the talo-crural joint in eight patients. The ages of the patients varied from 12 to 45 years (median age 24 years). Ten patients had previously sustained traumatic sprains. The duration of the symptoms was, on an average, two years (1-15 years). Radiographic examination of the talo crural joint revealed normal findings in all of the patients. Arthroscopically, in all of the patients, impingement of hypertrophic synovial tissue at the upper lateral corner of the talus was found. Trans-arthroscopic resection was performed with a shaver. A total of six patients became symptom-free and two experienced considerable relief of symptoms. The present authors have found the method to be suitable in selected cases of chronic pain in the talo-crural joint. PMID- 1858179 TI - [Recovery after ambulatory vasectomy]. AB - The recovery after outpatient vasectomy, with particular attention to general postoperative complaints, was investigated by means of a questionnaire. A material of 115 patients who were submitted to operation during the period 1.1.1988-31.12.1988 was covered by the investigation. Replies were obtained from 81%. The frequency of complaints/complications apart from the first 24 hours postoperatively was found to be unexpectedly high as 77% had from one to seven complaints/complications (average 2.8), pain and swelling being the commonest. 32% had complaints for three weeks or more while 90% were free from complaints after nine weeks. The secondary consequences of the complaints were apparent inconsiderable preoperative illness and a great number of postoperative contacts with the general practitioner. 23% had sick-leave for more than the first 24 hours postoperatively, 6% for more than one week and a total of 47 contacts with the practitioner occurred in 82 men. It is recommended that thorough information about the postoperative course should be provided by the departments in order to reduce the number of days of postoperative sick-leave and the number of contacts with the health services. PMID- 1858181 TI - [Meta-analyses: technical remarks]. PMID- 1858180 TI - [Duodenal ulcer in systemic mastocytosis]. AB - Two cases of systemic mastocytosis are presented. Both patients had peptic ulceration. Greatly raised values on investigation of gastric acid secretion in patients with therapy-resistant peptic ulceration and normal serum gastrin should raise the suspicion of systemic mastocytosis. PMID- 1858182 TI - [Continuous massive overdiagnosing of painter's syndrome (presenile dementia)]. PMID- 1858183 TI - [Screening or not--a difficult decision process]. PMID- 1858184 TI - [Non-dietary, non-pharmacological treatment of severe hypercholesterolemia]. AB - Non-dietary, non-pharmacological reduction of cholesterol in patients with severe hypercholesterolemia can be obtained by partial ileal by-pass, portacaval shunt operation or liver transplantation. A non-surgical method is apheresis, by which low density and very low density lipoproteins are removed from blood in an extracorporal circulation system. Apheresis methods include plasmapheresis, immunoadsorption, chemical affinity and Double Membrane Filtration. Treatment of a 30 year old man with severe familial hypercholesterolemia and ischaemic heart disease, by LDL-apheresis, resulted in an average decline in serum-cholesterol of 35%. LDL-apheresis is indicated in the treatment of this type of patient and in homozygous familial hypercholesterolemia. PMID- 1858185 TI - [Basal ganglia calcifications demonstrated by CT. Is further investigation necessary when this is found incidentally?]. AB - Calcification in the basal ganglia in the brain is, as a rule, asymptomatic and is therefore observed as an incidental finding at CT examination for other cerebral conditions e.g. tumours or haemorrhage. The question is whether incidental finding of calcification in the basal ganglia indicates the need for further supplementary investigations. Three case histories and study of the literature are quoted to illustrate this. It is concluded that investigation is not indicated in patients over the age of 50 years with limited, bilateral, symmetrical calcifications in the globi pallidi. In patients under 50 years, investigation in the form of detailed history taking, neurological examination and haematological investigation is indicated. PMID- 1858186 TI - [Pulmonary embolism]. AB - Acute pulmonary thromboembolism (PTE) is associated with considerable morbidity and mortality and may, if unrecognized, lead to severe chronic heart failure. Most cases are adequately treated with anticoagulants, while thrombolytic agents and other, more risky treatment regimens should still be reserved for the most severe cases. Even so, a definite diagnosis of PTE is prerequisite to any treatment, because of the risk of serious bleeding complications. However, the diagnosis of PTE is often difficult and always depends on confirmation by one or more diagnostic procedures, of which only pulmonary arteriography is of sufficient diagnostic value to be used alone. As pulmonary arteriography is costly and not without risk to the patient, the paper proposes a diagnostic strategy to limit the need for invasive procedures maximally without loss of diagnostic value. In critically ill patients with suspected PTE, bedside haemodynamic evaluation and balloon-occlusion-angiography may be valuable, as illustrated by two cases histories. PMID- 1858187 TI - [Attitudes to cholesterol measurement and intervention among general practitioners in Bornholm]. AB - In 1985 an explanatory report was published about investigation and treatment of hyperlipidaemia. This report, together with a consensus report published subsequently, formed the background for a nationwide cholesterol campaign. The attitudes of general practitioners to measurement of cholesterol and intervention must be considered to have decisive influence on performance of the goal of the consensus report, viz, reduction of the incidence of ischaemic heart disease (IHD). By means of a nine-page questionnaire, an attempt was made to assess the attitudes to measurement of cholesterol and intervention among the general practitioners on Bornholm. Out of the 35 questionnaires sent, 27 were returned (77%). Just under 40% of the general practitioners would screen all men aged between 20 and 59 years. Approximately 25% would screen women in the same age group. Opinions were unanimous about screening patients with diabetes, hypertension or IHD. Attitudes towards intervention were, by and large, in agreement with the cholesterol limits recommended in the explanatory report. In general, the general practitioners had well balanced attitudes towards tracing and treatment of individuals with raised serum cholesterol with relevant consideration of cholesterol as an important risk factor in the development of IHD. PMID- 1858188 TI - [Chorionic villi biopsy as an alternative to amniocentesis]. AB - The results of a retrospective assessment of the first 112 chorion villus biopsies carried out in the Department of Obstetrics and Gynaecology in the Central Hospital in Randers are presented. Karyotype determination was obtained in 98.2% and in 83.9% already by means of direct microscopic examination after incubation for 24 hours. No complications which could be attributed to the biopsies were registered. The present authors consider that the method should be employed more extensively for prenatal cytogenetic diagnosis. PMID- 1858189 TI - [Indomethacin enema in treatment of postoperative pain after knee arthrotomy. A double-blind controlled trial]. AB - Twenty-three patients subjected to arthrotomy of the knee were in a double-blind trial randomly allocated to either: 1) Indomethacin 100 mg (Confortid) administered as an enema immediately before induction of anaesthesia and repeated morning and evening for the next two days, or: b) a placebo. The patients' demand for postoperative pain treatment were registered. Survival analysis was applied to the time passed from recovery from anaesthesia until patients first asked for postoperative pain treatment. A significant difference was found (p less than 0.05). The indomethacin treated group required significantly less postoperative pain treatment than did the placebo group. 36% of the patients in the indomethacin group had no additional pain treatment during the two days of observation. Indomethacin as an enema proved to be an easy and effective way of reducing postoperative pain. PMID- 1858190 TI - [Cerebral symptoms in hyponatremia. Treatment and course]. AB - Pronounced hyponatraemia results in serious neurological symptoms and the untreated condition is associated with a great mortality. An account is presented of nine hyponatraemic patients (plasma sodium 101-119 mmol/l) without cardiac, renal or hepatic disease who were admitted to a department for intensive care. In all of the patients, consciousness was compromised. Three patients had generalized convulsions and six patients had respiratory involvement which required respirator treatment in two patients. In one patient, the hyponatraemia had developed acutely. The remaining cases had developed chronically. One patient was confused for one month after admission and another patient developed classical central pontine myelinolysis after a latent period of seven days and which required admission for rehabilitation for several months. The remaining patients, including the acute patient, had recovered completely after a few days. The rate of correction for plasma sodium was calculated for the patients. Animal experimental and clinical accounts concerning the pathological physiology and treatment of hyponatraemia are reviewed. It is important to differentiate between acutely and chronically developed hyponatraemia as treatments differ considerably. Severe chronic hyponatraemia should be treated with a rate of correction of plasma sodium of 0.5 mmol/l/hour, and the normal range for plasma sodium should be aimed at after a couple of days. The risk involved in more rapid normalization is development of central pontine myelinolysis with severe neurological sequelae. Hypertonic sodium chloride must only be employed in cases of acutely developed hyponatraemia with convulsions. Acute hyponatraemia may otherwise be corrected with a rate of correction of plasma sodium of 1 mmol/l/hour or more. PMID- 1858191 TI - [Clinical trial of an ergometry bicycle with automatic blood pressure registration]. AB - Automatic blood-pressure registration on a computerized ergometer cycle was compared with simultaneous manually registered blood-pressure employing a standard mercury sphygmomanometer during performance of maximal ergometer exercise testing on 50 consecutive patients. The difference in blood-pressure registered by the automatic and the manual methods, respectively, was, on an average +0.2 mmHg with a 95% confidence interval of +/- 20 mmHg. By means of linear regression analysis, a correlation coefficient of 0.97 (p less than 0.001) with an uncertainty of approximately 6% with automatic blood-pressure registration was found. Simultaneously, the uncertainty was independent of the degree of work performed. The apparatus was found to be of practical clinical use. PMID- 1858192 TI - [Acute compartment syndrome after a brief march]. AB - A case of acute anteriolateral compartmental syndrome in an 18-year old male conscript, caused by moderate physical strain is reported. It is questioned, with reference to literature, whether elevation and observation of mild cases is appropriate treatment. PMID- 1858193 TI - [Polycythemia vera in a Danish family]. AB - The occurrence of polycythaemia vera in a Danish woman and her two sons is described. No environmental agent could be identified and it is suggested that the cases represent a genetic susceptibility to this myeloproliferative disease. PMID- 1858194 TI - [Acute HIV infection after a single episode of oro-genital contact (fellatio)]. AB - Acute HIV infection with a papular rash is described in a homosexual man ten weeks after a single episode of orogenital contact (fellatio). The "safe sex" recommendations are discussed. PMID- 1858195 TI - [Mammography screening]. PMID- 1858196 TI - [Allergy tests in general practice]. PMID- 1858197 TI - [The comprehensive examination of patients with recurrent calcium nephrolithiasis]. AB - Hypercalciuria is one of the main causes of recurrent generation of urinary calcium-containing calculi. 107 patients with recurrent calcium nephrolithiasis were examined and results presented. Concentrations of potassium, sodium, chlorides, calcium, phosphorus, uric acid and creatinine were investigated in serum and urine, as well as indices of acid-base balance in arterial blood. pH metry, "preliminary" and oral calcium tolerance test were also carried out. The microcomputer data analysis established that the diagnosis of primary hyperparathyroidism may be identified in case of increased serum calcium level before and after calcium load test, the same of parathyroid, and increased urinary cAMP excretion. Renal hypercalciuria is characterized by low blood calcium level in both periods of the oral test, high basal calciuria, increased urinary cAMP excretion and its slight decrease after the oral calcium load test, by a tendency to lower serum magnesium levels in high magnesuria. The patients with absorptive hypercalciuria had an upper normal or increased blood calcium level, a significant calcemic and calciuric "response" to the calcium load, reduction in urinary cAMP elimination and more severe decrease (close to 0) of these indices after oral calcium load and normal magnesium levels in blood and urine. On a base of the "preliminary" test data the patients with relapsing calcium nephrolithiasis and metabolic disorders may be differed from those without calcium and phosphorus metabolic deteriorations. The "preliminary" test defines indications for the oral calcium tolerance test, automatic diagnosis and computer data storage facilitate physician to work and to solve problems of the patients' survey. PMID- 1858198 TI - [Ureteral remote shockwave lithotripsy]. AB - During 1-year exploitation of a Lithostar remote lithotriptor (Siemens) 221 patients with concrements of various parts of the ureter were treated. The patients' ages were from 6 to 86 years. It the course of treatment 170 patients needed only 1 session of remote shock wave ureterolithotripsy; 44--2 sessions; 5- 3; and 2--4 sessions. The ureterolithotripsy was carried out under intravenous and local infiltrative anesthesia, as well as under intravenous analgesia or without any anesthesia. According to presence or absence of the inflammation process, the time a concrement stood in the same place, the severity of obstructive nephropathy the following ureterolithotripsy methods were used: 1) "on the spot" (in the absence of inflammation and duration of concrement standing in one place no more than 6-8 weeks); 2) in the presence of an ureteral catheter (in more prolonged periods of concrement standing); 3) in the presence of transcutaneous puncture nephrostomy (in inflammatory process and severe signs of obstructive uropathy). Better treatment results were obtained in patients with a small concrement standing period and in those whose ureter concrements were shifted or passed the catheter. The retro- or anterograde concrement perfusion by physiologic saline and diuretic therapy increased the efficacy of remote shock wave ureterolithotripsy. The therapy was effective in 206 of 221 patients (93.2%); in case of failures 7 patients underwent an open ureterolithotomy; 5- retrograde and 3--anterograde ureteral stone extraction or lithotripsy. COMPLICATIONS: 6 patients had a pyelonephritis attack because of fragments crashed stone renal occlusion; 3 were operated on by the method of transcutaneous paracentetic nephrostomy; other 3 patients' kidneys were catheterized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858199 TI - [The selection of the method for urinary diversion in children]. AB - Ninety-five urinary fistulas have been produced at various urinary tract levels in 62 infants and children, aged 20 days to 13 years, for uni- or bilateral megaureter and hydronephrosis 14 days to 16 months prior to major reconstructive plastic surgery. Efficacy of draining (21 cystostomies, ureterostomies and nephropyelostomies) and nondraining (74 ureterocutaneostomies) techniques was evaluated 2-6 months or later using clinical, laboratory, X-ray, tracer and urologic cinematographic studies. Fistula application and removal maneuvers and complications are described. The draining techniques were found to be inefficient in prolonged preliminary urinary diversion and to be associated with frequent infection relapses and less satisfactory results of plastic surgery. Ureterocutaneostomy proved to be the most reliable and convenient method of prolonged drainage even though it required additional operations to replace the patent ureters. The drainage should be prolonged to 12-16 months if the urinary tract deteriorates, especially in young children. PMID- 1858200 TI - [Hemodynamics in transurethral operations under peridural anesthesia]. AB - Three types of cardiovascular system response were revealed in course of transurethral surgery. In the first 10-20 min after peridural anesthesia there was a decrease in total peripheral vascular resistance in all patients. This provided a positive effect in 84% of them as evidenced by normalized blood pressure, heart rate and cardiac output. In 8% of the operated on, lower total peripheral vascular resistance caused dangerous hypotension due to their weak compensatory mechanisms. 8% had a two-phase blood pressure decrease: firstly its decrease to subnormal levels was associated with lower total peripheral vascular resistance, but a repeated decrease (30-40 min later) in blood pressure to a critical level was initiated by a reduction in cardiac output and depletion of compensatory mechanisms, perhaps, due to a surgical hemorrhage. The both types of hemodynamic destabilization were easily corrected by an alpha-adrenomimetic drug (mezaton) infusions and graded intravenous administration. In case of a proper hemodynamic correction, the peridural anesthesia secured an optimal regime for the function of cardiovascular, respiratory and central nervous systems. PMID- 1858201 TI - [The conservative treatment of kidney cancer in middle-aged and elderly patients]. AB - Late results of conservative management were investigated in 102 patients with renal carcinoma. Their ages were 60 to 90. A symptomatologic therapy alone was used in the management of 60 patients, 38 were treated with hydroxyprogesterone capronate and 4 with nolvadex. All the patients suffered from concomitant diseases. The refusals of operative treatment were because of such causes as: 1) extension of the tumor process in 29; 2) severe intercurrent diseases in 41; 3) cancer of a single, single-functioning kidney or the both kidneys in 7; 4) the patients' refusals in 25 patients. After the described treatment 71.6% of them lived 1 year, 36.8%-3, and 26.2%-5 years, that was quite comparable with the postoperative results. Prognostically beneficial treatment criteria were: a patient's age of 70 or more years, the stage T1-2N0M0V0, asymptomatic course of the disease, absence of anemia, accelerated erythrocyte sedimentation rate (ESR) more than 40 mm/h; the tumor size less than 10 cm. The most unfavourable prognostic criteria were: T4 stage of the disease, decrease of a hemoglobin level lees than 80 g/l, tumor size more than 10 cm. No one of the 41 patients who had had at least of these signs survived over 3 years. The use of hydroxyprogesterone capronate had no advantages over the symptomatic therapy and did not prolong a patient's life. A 5-year survival of patients managed on hormonal therapy was 22%, on the symptomatic one, 27.1%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858202 TI - [The effect of psychoemotional stress on kidney function]. AB - Psychoemotional stress, like other kinds of emergency states, is accompanied by renal functional changes and accumulation of biologically active substances in the human body, among which middle molecular oligopeptides are classified. In inadequate or untimely premedication, an operative intervention of any scope occurs initially under unfavourable conditions due to accumulation of biologically active substances in blood and decrease in renal functions. The proposed method of preoperative measurement of the middle molecular oligopeptides and their correlations in plasma and urine may become an indirect indicator of premedication adequacy and a screening test of renal function. PMID- 1858203 TI - [The diagnostic and prognostic value of determining the content of beta 2 microglobulin in the blood and urine of potential kidney donors]. AB - The paper provides the results of a clinical observation of 20 potential kidney donors having various agonal periods. Significant changes in beta 2-microglobulin levels in blood and urine depending on the agonal duration were established. The nature of the changes in biological fluids suggest their significance in early diagnosis of renal ischemic lesions during the agonal period, as well as in the prognostic assessment of organ viability and functional adequacy. PMID- 1858204 TI - [Fine-needle aspiration and puncture biopsies in the diagnosis of lesions of kidney transplants]. AB - 270 fine needle aspiration and 41 puncture biopsies were fulfilled after 92 cadaveric renal transplantations to diagnose the status of the grafts. With the clinical and ultrasonographic data, the first method proved to be effective in diagnosing acute graft rejection in 79.9% of cases and in determining the status of graft reversibility or irreversibility, but the fine needle aspiration biopsy failed to differentiate the cellular or vascular types of the rejection. The method was also effective in diagnosing the tubular necrosis, acute cyclosporin nephrotoxicity, infectious transplant complications. The paracentetic biopsy essentially supplements the fine needle one and allows one to diagnose chronic cyclosporin nephrotoxicity and chronic transplant rejection. It appears to be the only method revealing the magnitude of graft rejection during oligoanuria caused by ischemic graft lesion. It was concluded that the results of fine needle aspiration biopsy were the most informative within the first postoperative month because later on it becomes difficult to obtain biopsy specimens adequate to interpret the results correctly. PMID- 1858205 TI - [Vitamin K1 and C metabolism in uremia during hemodialysis]. AB - Plasma concentrations of vitamin K1, ascorbic acid and its derivatives were investigated in uremic patients during a session of systemic hemodialysis at the dialyzers input, output and in dialyzing solution. The data showed practically unchanged clearances of vitamin C and diketogulonic acid during the session of hemodialysis. In the course of its passage through the dialyzer, plasma ascorbic acid was partially oxidized to dehydroascorbic acid, partially it converted to a dialysate, partially it returned to the human body. Plasma level of vitamin K1 in uremic patients was 1.8 times lower than that in the healthy; 24-hour its excretion in uremic patients and in the healthy was similar. It is supposed that the vitamin K1 decrease correlates with lipoid changes in uremia. During a session of hemodialysis no significant vitamin K1 losses were revealed. PMID- 1858206 TI - [The role of the phenomenon of the redistribution of aminoglycosides in their monitoring and dosage calculation in patients in the terminal stage of kidney failure undergoing systematic hemodialysis treatment]. AB - The kinetics of aminoglycosides (amikacin, netilmycin, gentamicin, tobramycin) were investigated in patients with end-stage renal disease who were on systemic hemodialysis. Their decrease in the blood revealed in pre-dialysis and dialysis periods was exponential. After dialysis termination there was a gradual aminoglycoside increase as compared to the end-dialysis period, which was of linear character and depended on the degree of these agents' dialysis clearance. The cause of the phenomenon is likely to be higher aminoglycoside blood elimination rate than their entering the blood from tissues. A method is proposed to calculate an additional dose of aminoglycosides, taking into account their higher concentrations in the postdialysis period, under permanent monitoring of their blood levels. PMID- 1858208 TI - [The participation of the kallikrein-kinin system in edema formation in glomerulonephritis]. AB - Involvement of the kallikrein-kinin system in the pathogenesis of renal edemas may be mediated by increase of vascular permeability, proteinuria, diuresis and natriuresis. Proceeding from these points, in 27 patients with morphologically proved chronic glomerulonephritis and the nephrotic syndrome, the serum kallikrein activity and its 24-hour urinary excretion level were measured. According to their edematous syndrome severity, all the patients were divided into 2 groups: 1) 19 patients with moderate edemas; 2) 8 patients with severe ones. During the follow-up period, there were no essential changes in patients' body weights, and no significant differences between the groups in clearances and excreted fractions of sodium, potassium, chlorine, osmotically active substances, and in serum albumin and cholesterol levels, 24-hour protein losses and blood pressure. As compared to the healthy (n-20) in all the patients a substantial and statistically significant increase in kallikrein activity was revealed in serum and urine. Kallikreinemia and kallikreinuria were significantly higher in Group 2 than those in Group 1. In the total group of examinees a significant direct relationship was established between the urinary kallikrein activity and summary sodium and potassium excretion as well as between the serum kallikrein activity and chlorine clearance. A direct correlation between the serum kallikrein activity and proteinuria was also found. Thus, a role of the kallikrein-kinin system in development of glomerulonephritic edemas concurrent with the nephrotic syndrome is hetero-directional.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858207 TI - [Intravesical distension in the corrugated tuberculotic bladder]. AB - The treatment problem of urinary tract post-tuberculous changes is not completely solved. Current methods do not always give good results and are accompanied by some complications. The authors describe their own modified method of hydrostatic intravesical distension of the tuberculotic-cirrhotic bladder, using epidural anesthesia, and worked out indications for it. The results show an increase in the bladder volume from 100-120 to 250-300 ml with a decreased urination frequency in 8 patients. The method occurred to be very convenient-to-use due to the absence of any complications. PMID- 1858209 TI - [The effect of diabetic nephropathy on the function of the hypophyseal-gonadal system in men]. AB - The functional state of the hypophyseal-gonadal system was investigated in 160 males suffering from Types I and II diabetes mellitus. There were no correlations revealed in the incidence and severity of sexual dysfunction according to the patients' ages, diabetes type and duration. The sexual disturbances correlated with the severity of diabetic microangiopathy (r = +0.48) and a state of diabetic compensation (r = +0.36). The development and progression of diabetic nephropathy was accompanied by a rise of blood luteinizing and follicle-stimulating hormones and a drop of testosterone, estrogen-androgen imbalance. PMID- 1858210 TI - [X-ray endovascular research in varicocele in children]. AB - 60 patients with varicocele first diagnosed and 38 with postoperative recurrences of varicocele were examined with use of digitalis subtraction renal and testicular phlebography as an optional diagnostic method. In the patients' group with varicocele recurrences the roentgeno-endovascular method allowed the causes of relapses associated with inadequate ligation of testicular vein influxes to be revealed (73.3%) and collateralization of the operated region (26.3%). In patients with firstly diagnosed varicocele the phlebography confirmed the diagnosis in 98.3%; revealed associated urogenital diseases; allowed indications for a specific mode of surgical correction to be formulated. 78 patients underwent testicular vein roentgeno-endovascular occlusion with 3% solution of thrombovar, 15 were operated on by the method of Ivanissevich in whom a level and character of surgical ligation were defined by phlebographic data; one patient had the operation testicular-saphenous anastomosis; one patient was not operated due to his systemic blood disease. By digitalis subtraction angiographic data recurrence rates after a proper treatment were 2%. 4.1% had thrombophlebitis of the racemose plexus after a sclerotherapy conservatively abolished. The use of digitalis subtraction testicular phlebography allowed one to properly choose a surgery and to decrease relapse rates due to its high preoperative diagnostic efficacy. In addition, preoperative X-ray endovascular examination made it possible to reveal the cause of relapses after early performed operations, to detect synchronous renal lesions in time, and to prevent recurrences by reducing the amount of a contrast medium by a factor of 2-3. PMID- 1858211 TI - [Cavernous hemangioma of the pelvis-ureter segment complicated by hydronephrosis and urolithiasis]. PMID- 1858213 TI - [A giant stone in the posterior urethra]. PMID- 1858214 TI - [A case of a long-term asymptomatic course in a foreign body of the prostate]. PMID- 1858212 TI - [Calcinosis of the ductus deferens]. PMID- 1858215 TI - [Uremic middle-molecule toxins and their removal in hemofiltration]. PMID- 1858216 TI - [The functional activity of the urethral neutrophilic granulocytes in patients with chronic urethroprostatitis and its correction]. AB - The functional state of urethral neutrophil granulocytes in patients with chronic urethro-prostatitis, and possibility of miramistin use in complex treatment of the disease were investigated. The data revealed functional suppression of these granulocytes in the patients. Complex treatment with miramistin normalized indices of urethral phagocytic activity, on the contrary, after treatment of the patients without the agent there was no tendency to normalize urethral phagocytic function. The findings suggest that miramistin supplemented to routine antiinflammatory therapy improves curative results in patients with chronic urethro-prostatitis but the drug should be prescribed in accordance with the initial function of urethral neutrophil granulocytes. PMID- 1858217 TI - Elastography: a quantitative method for imaging the elasticity of biological tissues. AB - We describe a new method for quantitative imaging of strain and elastic modulus distributions in soft tissues. The method is based on external tissue compression, with subsequent computation of the strain profile along the transducer axis, which is derived from cross-correlation analysis of pre- and post-compression A-line pairs. The strain profile can then be converted to an elastic modulus profile by measuring the stresses applied by the compressing device and applying certain corrections for the nonuniform stress field. We report initial results of several phantom and excised animal tissue experiments which demonstrate the ability of this technique to quantitatively image strain and elastic modulus distributions with good resolution, sensitivity and with diminished speckle. We discuss several potential clinical uses of this technique. PMID- 1858218 TI - An efficient algorithm to remove low frequency Doppler signals in digital Doppler systems. AB - In color flow imaging, a high flow map rate in combination with a reasonable width of the map and good velocity resolution is essential to properly appreciate the time-dependent phenomena. The velocity resolution depends on the length of the signal segment considered in combination with the settling time of the high pass filter used to eliminate transients and low frequency artifacts. The latter can be reduced by appropriate processing. This paper presents an algorithm to suppress low frequency Doppler signals effectively and efficiently, while all the data points within the segment considered contribute equally to the average Doppler frequency computed. The algorithm is applied to computer generated Doppler signals to evaluate their time and frequency behavior. It is concluded that the proposed scheme functions adequately under various signal conditions. PMID- 1858219 TI - Experimental evaluation of the correlation interpolation technique to measure regional tissue velocity. AB - A newly developed correlation interpolation method to measure the regional velocity of moving tissue is evaluated in an experimental setup. Pulsed ultrasound echo signals (center frequency 3.5 MHz) are received from a rotating Agar disk containing scattering particles. When averaging over a depth range of 2.2 mm at a pulse repetition frequency (PRF) of 930 Hz, the standard deviation of the measured displacement between 2 successive pulses was found to be +/- 6 microns. In a second series of experiments, the angular velocity of the disk is estimated from the displacement, as measured simultaneously in two different regions located on separate echo lines (PRF = 465 Hz per line). The exact position of both regions in respect to the center of rotation was found to be irrelevant. The accuracy of the calculated angular velocity was found to be better for large angles between the two lines of observation than for small angles. PMID- 1858220 TI - Ultrasonic imaging and tissue characterization. June 3-5, 1991, Arlington, Va. Abstracts. PMID- 1858221 TI - [Experience in long-term clofelin use in the treatment of glaucoma]. AB - A long (4-14 years, the mean period 7.8 +/- 1.5) follow-up of 52 patients with primary open-angle glaucoma, regularly administered clofelin instillations (over the entire follow-up) has demonstrated a manifest hypotensive and a good functional result of such therapy. Despite reduction of systemic arterial pressure induced by clofelin instillations, rheo-ophthalmography has shown enhanced blood stream in ocular vessels. 52 percent of patients were administered no miotics but only clofelin (16 patients, 28 eyes) or clofelin+timolol (11 patients, 17 eyes). PMID- 1858222 TI - [Acute attacks in pseudoexfoliative glaucoma]. AB - Clinical picture and the results of treatment of an acute attack in 23 eyes with open-angle pseudoexfoliative glaucoma are presented. A total of 47.9 percent of patients were hospitalized with erroneous diagnoses of neovascular, phacolytic, uveal, phacotopic glaucoma or suspected neoplastic process. Blurred clinical picture of the acute attack could be responsible for the erroneous diagnosis: the painful syndrome was not manifest, the anterior chamber depth and pupil width were normal, the patients presented with insignificant corneal edema and rubeosis, posterior synechia, hyphema, and iridophacodonesis. Gonioscopy showed an open anterior chamber angle with manifest exogenic pigmentation of all the areas and with endogenic pigmentation of Schlemm's canal. Sinuso-trabeculectomy or deep sclerectomy was carried out in 20 eyes, in 8 eyes with cataract extraction. Expulsive hemorrhages occurred in 2 eyes, in 1 case eventuating in enucleation. Primary enucleation was carried out in 3 blind eyes. Surgery resulted in normalization of intraocular pressure in 19 eyes. Vision acuity of 0.1-0.3 diopters was achieved in 6 eyes, 0.02-0.08 in 8 eyes, and remained 0 in 5 eyes. Glaucoma was developing in 3 eyes, far-advanced in 15, and terminal in 1. The authors claim that dystrophic changes of ocular tissues are a characteristic feature associated with acute attacks in pseudoexfoliative glaucoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858223 TI - [Method of lensectomy in high myopia]. AB - The authors suggest a method of removing a transparent lens in high myopia patients aged over 40 with a dense lens nucleus. The method consists of 3 stages. Stage I consists in preliminary intracapsular YAG laser fragmentation of lenticular fibrils, performed 2-4 days before surgery. Stage II consists in YAG laser anterior capsulotomy directly before lens extraction. Stage III consists in lenticular mass aspiration irrigation via 2 small incisions on the cornea. The described lensectomy method was used in 23 patients (44 eyes) aged 40 to 55 with refraction of 16.0 to 23.0 diopters. The time of lenticular mass aspiration was cut down by half as against that after lensectomy without preliminary intracapsular YAG laser fragmentation of lenticular fibrils. No complications during or after surgery were recorded. After surgery vision acuity improved by 13 times without correction and two times with correction. PMID- 1858224 TI - [Prediction of functional results of extraction in complicated cataract in patients with tapetoretinal abiotrophy]. AB - Relative informative value of various functional methods of investigation was studied in 87 patients with tapetoretinal abiotrophy and complicated cataracts in order to find adequate methods for the assessment of the retinal status before surgery and to define the criteria of visual function prediction. The efficacy of the diagnosis was verified after cataract extraction in these patients. The methods of investigation employed were instrumental electroretinogram (ERG) recording, Hanz-Feld stimulated microERG, high-frequency (40 Hz) rhythmic ERG, electrocoagulograms, determination of electric sensitivity thresholds for the retina and of the optic nerve axial bundle lability (ESL), perimetry, and vision acuity measurements. Rhythmic ERG and ESL were found the most informative; rhythmic ERG amplitude proved to be the most sensitive to macular area involvement, this prompting employment of this method for the prediction of visual functions. Rhythmic ERG helped single out three groups of patients with relatively favorable, doubtful, and unfavorable outcomes. PMID- 1858225 TI - [Outcomes of circular tunnel keratoplasty]. AB - A new refraction operation for the correction of medium and high myopia, circulatory tunnel keratoplasty, has been theoretically validated, developed, experimentally tested, and tried in clinic. Experiments included 8 tested, in isolated cadaveric eyes and 72 surgeries on 39 rabbits. Experiments helped develop surgical equipment and technique. A relationship between the refraction effect and the diameter of the circulatory tunnel and implant thickness has been revealed. Time course of the refraction effect has been followed up for up to 2 years. The refraction diminished from 4.0 to 11.0 diopters. Thirty eyes of 21 patients with stable myopia of 6.0 to 22.0 diopters were operated on with the resultant refraction of 6.0 to 14.0 diopters. The results have confirmed the relationship between the refraction effect of surgery and the implant thickness. The authors claim that circulatory tunnel keratoplasty is an effective method for the correction of medium and high myopia and recommend it for clinical application. PMID- 1858226 TI - [Extrascleral ballooning. 2. New approaches: double and sector ballooning]. AB - Treatment of retinal detachment with the use of distended balloons (extrascleral ballooning) holds good promise due to ease of operation and low traumatism. Unfortunately it may be used only in cases with fresh not high detachments of the retina with solitary or multiple ruptures up to 1-2 optic disk diameters in length. That is why the authors suggest two new modifications of the method: double and sector ballooning, widening the indications for the employment of the method. Double ballooning is recommended for cases with retinal detachments with 2 ruptures up to 2 disc diameters in length, located at a distance of 2-3 disc diameters from each other within one quadrant or in different quadrants of the fundus oculi. Sector ballooning is recommended for cases with retinal detachments with ruptures or breaks off 3-6 disc diameters in length. The results of 24 surgeries are analyzed. Double ballooning is effective in 77 percent of cases, sector ballooning in 82 percent. The presence of proliferative vitreoretinopathy, stages C3-D, is a contraindication against the use of this technique. PMID- 1858227 TI - [A new method of duplex ultrasonic examination of the state of blood supply to the ciliary body]. AB - Duplex ultrasonic scanning was used to examine blood supply to the ciliary body. The study helped quantitatively assess the ciliary body hemodynamics. The hemodynamic parameters in diseases of the anterior segment of the eye (cataracts, glaucoma, corneal dystrophy, etc.) significantly differed from the norm: pulsative index 2.32 vs. the normal value of 1.57, systolic/diastolic ratio 7.29 vs. 6.23, the peak systolic rate 12.59 cm/sec vs. 34.36 cm/sec, maximal rate 6.56 cm/sec vs. 14.36 cm/sec, mean rate 4.0 cm/sec vs. 8.76 cm/ces, volumic rate 1.47 ml/min vs. 3.66 ml/min. The examinations helped detect early disorders in the blood supply to the ciliary body. New ultrasonic equipment: Quantascope (Vital Science, England) and DRF-1000 (Piasonics, USA) was used, that proved highly informative and reliable. PMID- 1858228 TI - [Hemosorption in multimodal treatment of endogenous uveitis]. AB - Hemoperfusion was used in multiple modality treatment of 92 patients with chronic recurrent endogenic uveitis and uveitis associated with syndromic conditions. The treatment included systemic and local steroids, and antiinflammatory therapy. Clinical improvement was achieved in 75 percent of patients; it was paralleled by improvement of the vision acuity. In the rest patients vision acuity was unchanged because of irreversible impairment of the retina and optic nerve, but uveitis ceased. Addition of hemoperfusion of multiple-modality treatment of uveitis patients resulted in shortening of hospital stay by 6-7 days, in prolongation of remission periods to 10-15 months after a single course of hemoperfusion in 71 percent of patients and after two courses in the rest. A dynamic immunologic analysis has shown normalization of T lymphocyte functional activity, and of blood serum immunoglobulin and circulating immune complexes levels. PMID- 1858229 TI - [Immuno-correcting therapy of sympathetic ophthalmia]. AB - Exchange plasmapheresis was used in correction of the immune homeostasis in 5 patients with sympathetic ophthalmia. The inflammatory process ceased in all the cases. Exchange plasmapheresis resulted in improvement of the blood supply to ocular vessels, of intraocular vessel function, and of metabolic processes in the external layers of the retina. Cellular and humoral immunity parameters normalized. The hemo- and hydrodynamic parameters of the eye improved; all these results evidence that exchange plasmapheresis is an effective method in the treatment of sympathetic ophthalmia. PMID- 1858230 TI - [Role of enterovirus infection in the etiology of uveitis in children]. AB - A total of 224 cases with endogenic uveitis in infants are analyzed. The results of complex clinical and immunological analysis and serologic findings bring the authors to a conclusion that enteroviral uveitis makes up 42 percent of all uveitis in children aged under 3 and that this condition is prevalent in this country. Typical late complications, long persistence of virus-neutralizing antibodies in high titers (up to 8-10 years after convalescence) permit a retrospective etiological diagnosis. PMID- 1858231 TI - [Chromatopsia]. AB - A total of 277 chromatopsia cases (0.09 percent of the total number) are analyzed, including erythropsia, xanthopsia, cyanopsia, chloropsia, and polychromatopsia. True chromatopsia and chromatopsia due to staining of optic media of the eyes were distinguished and an attempt to explain this entoptic phenomenon made. True chromatopsias are related to depression of stimulation of the optic nerve route. PMID- 1858232 TI - [Computerized tomography in the evaluation of the state of the orbit and its contents in patients with post-traumatic anophthalmos]. PMID- 1858233 TI - [Syndromic uveitis in Reiter's disease]. AB - The authors describe the clinical picture of various forms of anterior and posterior uveitis associated with Reiter's disease in 28 patients; both eyes were involved in 11 of these. The data of laboratory tests for ophthalmic and urogenital chlamydiasis in these patients are presented; a relationship between uveitis clinical forms and Chlamydia detection rate in the conjunctiva and urethra has been revealed. Different pathogenesis of uveitis clinical forms is discussed and the necessity of their differentiated therapy emphasized. PMID- 1858234 TI - [Experience in the organizational activities of a service for rehabilitation of patients with sequelae of eye injuries]. PMID- 1858235 TI - [Characteristics of physiopathology, clinical aspects and optical correction in congenital myopia. Literature review]. PMID- 1858236 TI - [Use of botulinum toxin in ophthalmology (literature review)]. PMID- 1858237 TI - [Organization of ocular prosthetics in the USSR]. PMID- 1858238 TI - [Anatomo-topographical features of the oblique muscles and their surgery (literature review)]. PMID- 1858239 TI - Clinical approach to infertility in bitches with primary anestrus. AB - In conclusion, a complete workup of the bitch that has not shown a puberal estrus by 24 months of age should include a general screen with hemogram, chemistries profile and urinalysis, karyotype, serum thyroid hormone profile, serum progesterone concentration, and serum luteinizing hormone concentration, if available. If the results of these tests are normal, an exclusion diagnosis of immune-mediated oophoritis, which can be confirmed by ovarian biopsy, should be considered. Bitches with primary anestrus secondary to thyroid insufficiency or chronic debilitating disease may show normal reproductive cycling and performance after successful treatment of these disorders; in other patients, prognosis for future reproduction is poor. PMID- 1858240 TI - Canine reproduction. PMID- 1858241 TI - Clinical approach to infertility in the cycling bitch. AB - The majority of "infertile" bitches presented to the practitioner are victims of mismanagement. Careful evaluation of reproductive history, physical examination, and vaginal cytologic evaluation permit conception in these patients. Measurement of serum progesterone levels can help establish occurrence and timing of ovulation. Diagnosing true reproductive problems may require a minimum data base, guarded cultures, vaginoscopy, vaginography, ultrasound, and ultimately laparotomy for uterine biopsy and culture. The majority of these diagnostic procedures are readily available for the interested practitioner. PMID- 1858242 TI - Diagnostic imaging of the reproductive organs of the bitch. Methods and limitations. AB - This article reviews diagnostic radiology and ultrasonography of the reproductive tract of the bitch. The techniques and limitations of these imaging modalities are described. The applications of these techniques in the bitch for illustrating reproductive disorders are included. PMID- 1858243 TI - Achieving canine pregnancy by using frozen or chilled extended semen. AB - Successful artificial insemination in the dog requires good timing of the insemination, skilled collection and handling of the semen, and mastering of insemination techniques. The bitch should be inseminated late in estrus. The insemination dose should contain at least 150 to 200 x 10(6) spermatozoa. Fresh semen can be inseminated vaginally, whereas frozen-thawed semen should be inseminated into the uterus. Pregnancy rates of 84% with fresh semen and 69% with frozen semen are reported. PMID- 1858244 TI - Use of prostaglandin F2 alpha for early pregnancy termination in the mismated bitch. AB - Natural PGF administered at a dose of at least 250 micrograms/kg twice daily subcutaneously for at least 4 days starting no earlier than day 5 of cytologic diestrus induces luteolysis and pregnancy termination in the mated bitch. The resulting shortening of the luteal phase is associated with a shortening of the interestrous interval from 1 to 4 months. Bitches treated with PGF show emesis, diarrhea, and panting within 5 minutes and transient hypothermia which lasts 2 to 3 hours but generally have no further reaction. Bitches with cardiac or respiratory dysfunctions are not considered safe patients for early pregnancy termination with PGF because of the cardiovascular effects of this drug. Bitches treated with this regime early in diestrus resorb their conceptuses; those treated after days 35 to 40 show clinical abortion of viable fetuses. PMID- 1858245 TI - The ovarian remnant syndrome in the bitch and queen. AB - The ovarian remnant syndrome is a complication of ovariohysterectomy resulting in the presence of functional ovarian tissue in the abdomen. The usual symptom is a return to estrus in a previously ovariohysterectomized bitch or queen. The available methods of diagnosis are vaginal cytologic evaluation during estrus, resting hormone assays, hormone challenge testing, and exploratory laparotomy. Surgical removal of the ovarian remnant is the preferred treatment. PMID- 1858246 TI - Clinical approach to vaginal/vestibular masses in the bitch. AB - The most common causes of vaginal/vestibular masses in the bitch are vaginal prolapse, vaginal neoplasia, and urethral neoplasia protruding into the vaginal vault. Other possible causes are clitoral enlargement, vaginal polyps, uterine prolapse, and vaginal abscessation or hematoma. Vaginal prolapse usually can be distinguished from neoplasia by the age of the patient, the time of occurrence during the estrous cycle, and the site of origin of the mass. Prolapse usually occurs in bitches under 4 years of age during proestrus, estrus, or at the end of diestrus and usually arises from the floor of the vagina, except for urethral tumors that protrude from the external urethral orifice. Appropriate diagnostic workup of bitches with vaginal vestibular masses includes complete history and physical examination, vaginal cytologic and vaginoscopic examination, retrograde vaginography or urethrocystography, serum progesterone and estradiol concentrations, and, in the case of suspect neoplasms, surgical or excision biopsy of the mass. PMID- 1858248 TI - Performing a complete canine semen evaluation in a small animal hospital. AB - Normal dog semen ranges in volume from 1 to 30 mL per ejaculate and contains 300 million to 2 billion sperm, of which more than 70% are progressively motile and morphologically normal. Dog semen should contain fewer than 10,000 bacteria per mL; higher numbers are indication of an infection of the male reproductive tract and usually are associated with cytologic evidence of inflammation (neutrophils in semen sediment) and with decreased progressive motility and decreased numbers of morphologically normal sperm. Measurement of pH of seminal plasma of dogs with infection of the reproductive tract may provide information on determining the choice of antibiotic. Measurement of seminal plasma alkaline phosphatase in azoospermic dogs is an indicator of tubular patency to the level of the epididymides. PMID- 1858247 TI - Diagnosis and treatment of chronic vaginitis in the bitch. AB - The diagnosis of chronic vaginitis is made primarily on the basis of the historical and physical finding of a persistent, nonhemorrhagic vulvar discharge. Licking the vulva and pollakiuria are present in some (10%) bitches with vaginitis. The diagnosis can be confirmed with vaginal cytology and vaginoscopy. Treatment for vaginitis in bitches younger than 1 year of age is justifiably conservative, because the majority of such bitches (90%) recover with or without treatment. Chronic vaginitis in bitches older than 1 year of age most often is associated with identifiable abnormalities of the genitalia (35%) or urinary tract (26%). Resolution of the vaginitis is directly related to the resolution of the other abnormalities. PMID- 1858249 TI - Diagnostic imaging of the male canine reproductive organs. Methods and limitations. AB - Survey radiographic, contrast radiographic, and ultrasonographic techniques for evaluation of the male canine reproductive organs are reviewed. The applications and limitations of these technique as they apply to reproductive diseases involving the prostate gland and testicles are illustrated. PMID- 1858250 TI - Clinical approach for evaluating dogs with azoospermia or aspermia. AB - There are various causes for azoospermia and aspermia in dogs. Unfortunately, even when the site and cause of infertility are determined, reversing the disorder may be difficult. As new information are gathered on the maturation of canine spermatozoa, testicular immunity, microsurgical techniques for anastomosing occluded ducts, and the physiologic control of testicular and ejaculatory function, however, new therapies might be developed to prevent or reverse azoospermia and aspermia. PMID- 1858251 TI - Clinical approach to infertile male dogs with sperm in the ejaculate. AB - Categories of infertility are defined according to semen characteristics. Assessment of daily sperm output and carefully planned matings to determine the extent of infertility and to manage insemination to maximize fertility are described. The contributions of baseline laboratory data, evaluation of reproductive hormones, and testicular biopsy in determining the causes of infertility are discussed. Treatments of infertility secondary to systemic disease, infertility caused by accessory gland infections, and infertility associated with abnormal gonadotropin concentrations are reviewed. PMID- 1858252 TI - Lectin histochemistry of trachea and lung of healthy turkeys (Meleagris gallopavo) and turkeys with pneumonia. AB - Thirteen lectins were used to characterize lectin-binding specificity of glycoconjugates on sections of formalin-fixed lung and trachea from seven normal turkeys, two turkeys with acute pneumonia, and two turkeys with chronic pneumonia. Neuraminidase was used to digest sialic acid residues. One N acetylgalactosamine-binding lectin and two N-acetylgalactosamine/galactose binding lectins stained the apical membrane and cytoplasm of multifocal cells that lined air atria and hyperplastic granular cells. Other lectins in these groups stained ciliated cells of the trachea and bronchi and air capillary epithelial cells. Sialic acid residues were on apical surfaces of ciliated and nonciliated tracheal and bronchial lining cells, air capillary epithelial cells, and vascular endothelial cells. Mannose/glucose-binding lectins stained reticular and elastic fibers in the lamina propria of trachea, primary and secondary bronchi, and the tunica adventitia of arteries and veins. By transmission electron microscopy, colloidal gold-Arachis hypogaea (peanut agglutinin) labeled microvilli on the apical surface of mature granular cells. The L-fucose-binding lectin, in addition to several other lectins, stained nonspecifically in both trachea and lung. These studies show that granular cells that line air atria can be identified with lectins of N-acetylglucosamine and N acetylgalactosamine/galactose groups, and that apical surfaces of epithelial cells and endothelial cells in the trachea and lung express terminal sialic acid residues. PMID- 1858253 TI - Passive role of articular chondrocytes in the pathogenesis of acute meniscectomy induced cartilage degeneration. AB - The importance of viable articular chondrocytes and enzymes or factors from surgically traumatized synovium in the pathogenesis of acute meniscectomy-induced cartilage degeneration was examined in guinea pigs (nine groups of five animals each). Iodoacetate injected intra-articularly was used to kill articular chondrocytes of guinea pigs prior to meniscectomy to determine if they were active participants in the acute lesion induction. Lesions of similar severity to those occurring in animals with viable chondrocytes at the time of surgery were observed, suggesting that the chondrocytes were not actively involved in the pathogenesis in this group. In an additional group of guinea pigs in which chondrocytes were killed by iodoacetate, the medial collateral ligament was transected to determine if acute degenerative changes could be induced in acellular cartilage exposed to a surgical manipulation that does not by itself induce lesions but does expose cartilage to enzymes/factors from traumatized synovium. Transecting the medial collateral ligament and entering the joint space without induction of instability via meniscectomy did not result in histologic evidence of cartilage damage. This suggests that synovial trauma and mild inflammation were insufficient to induce matrix degeneration in the absence of abnormal load bearing. In further support of this, guinea pigs subjected to unilateral sciatic neurectomy at the time of meniscectomy were protected against development of acute cartilage degeneration. Results of this study suggest that articular cartilage devoid of viable chondrocytes at the time of meniscectomy responds acutely in much the same way as intact cartilage subjected to this procedure. PMID- 1858254 TI - Congenital anemia, dyskeratosis, and progressive alopecia in Polled Hereford calves. AB - A new syndrome of anemia, alopecia, and dyskeratosis was identified in Polled Hereford calves in this study. Cutaneous changes included hyperkeratosis and hair loss around the muzzle and ear margins, which progressed to a generalized alopecia and hyperkeratotic dermatitis. Histologically, orthokeratotic hyperkeratosis with dyskeratosis of epidermal and follicular keratinocytes was present. Alopecia was correlated with dyskeratosis of Huxley's layer and an increasing proportion of follicles in the telogen phase of the hair cycle. Dermatitis was characterized by a mild dermal mononuclear cell infiltrate and mild lymphocytic perivascular dermatitis. The anemia present at birth was nonprogressive and was classified as normochromic and normocytic to macrocytic. Reticulocytosis was absent, but bone marrow was markedly hyperplastic. Nuclear cytoplasmic asynchrony of the rubricyte and metarubricyte stages occurred in the bone marrow. Abnormal rubricyte nuclei and maturation arrest at the late rubricyte stage were common. Cytologic features of the erythroid series are similar to those of type I congenital dyserythropoietic anemia of human beings. Genealogic features suggest that this is a primary hereditary defect. The mode of inheritance, however, remains to be determined. PMID- 1858255 TI - Eight cases of canine lymphomatoid granulomatosis. PMID- 1858256 TI - An anaplastic astrocytoma (glioblastoma) in the cerebellum of a dog. PMID- 1858257 TI - Hypoplastic left ventricle and aortic atresia in a calf. PMID- 1858258 TI - Pulmonary blastoma in a rat. PMID- 1858259 TI - Do hares suffer from grass sickness? AB - An autopsy study of one dead and two sick hares from an East Anglian estate on which two mares had died of grass sickness revealed that two of the hares were suffering from a polyganglionopathy and alimentary tract changes, remarkably similar to those seen in grass sickness in horses. No such abnormalities were found in two healthy hares from the same locality. PMID- 1858260 TI - Effect of husbandry system on broken bones and bone strength in hens. AB - The effects of rearing system, forced moulting and three different layer housing systems on broken bones and bone strength, were examined in hens at the end of lay. Weak bones and broken bones were more common in battery hens which had been reared to point of lay on deep litter rather than in cages. The incidence of old breaks was greater in perchery birds (14 per cent) than in tiered terrace birds (5 per cent), and there was also a difference between their incidence in two types of perchery design (17 per cent and 11 per cent). Moulting was associated with a transient decline in bone strength, followed by an increase in strength during the second lay. PMID- 1858261 TI - Apparent decline in fertility in heifers after repeated oestrus synchronisation with cloprostenol. AB - Over several years groups of heifers which were repeatedly treated with the PGF2 alpha analogue, cloprostenol, to synchronise oestrus were artificially inseminated. When sperm treatment was optimised, a reduction in conception rate was observed which was related to the number of synchronisation treatments the animals had received. Although factors such as a seasonal reduction in fertility may have contributed to the effect, there appeared to be a decrease in the proportion of animals becoming pregnant after successive synchronisations. Possible explanations for this observation are suggested. PMID- 1858262 TI - Avian tuberculosis dermatitis in a young horse. PMID- 1858263 TI - Aggression in golden retrievers. PMID- 1858264 TI - Withdrawal of Alugan. PMID- 1858265 TI - Renal failure in bull terriers. PMID- 1858267 TI - Rhododendron poisoning. PMID- 1858266 TI - Red deer, nematodes and anthelmintics. PMID- 1858268 TI - Tumours in Russian hamsters. PMID- 1858269 TI - Animal behaviour. PMID- 1858270 TI - Bacterial flora of the uterus of cows after calving on two hygienically contrasting farms. AB - Intrauterine swabs were obtained from cows after calving on two commercial dairy herds with contrasting hygienic environments and incidence of leucorrhea, and cultured aerobically and anaerobically. Of 26 cows with a normal calving and puerperium, eight of 14 (57 per cent) were sterile on farm B where hygiene was poor, compared with five of 12 (42 per cent) on farm A where hygiene was better. Two cows on farm B retained their placentas and subsequently developed metritis/endometritis. Actinomyces pyogenes was the commonest bacterial isolate and Fusobacterium nucleatum, Proteus mirabilis and Bacteroides melaninogenicus were also frequently observed. Similar isolates were obtained from cows on farm B with parturient or puerperal disorders. The contrasting hygienic environments had no influence on either the quantitative or qualitative uterine bacterial flora. Thus, the difference in the incidence of endometritis must have been due to factors other than hygiene. PMID- 1858271 TI - Effect of slaughter by removal from water on visual evoked activity in the brain and reflex movement of rainbow trout (Oncorhynchus mykiss). AB - The effects of removal from water and death by anoxia on brain function and reflex movement were examined in conscious trout. Visual evoked responses (VERS) were measured in fish with a body temperature of 20 degrees C, 14 degrees C and 2 degrees C. On average the fish took 2.6 minutes at 20 degrees C, 3.0 minutes at 14 degrees C and 9.6 minutes at 2 degrees C to lose VERS, and 11.5, 27.7 and 197.6 minutes, respectively, to lose all movement. VERS were absent from fish anaesthetised with MS222. From a humanitarian standpoint these results indicate that fish killed by anoxia could be exposed to periods of distress or suffering, and that cooling them in ice prolongs this period. PMID- 1858272 TI - Fertility of a stallion with low sperm motility and a high incidence of an unusual sperm tail defect. AB - At the beginning of the breeding season an eight-year-old standardbred stallion had semen with virtually zero sperm motility and an approximately 90 per cent incidence of midpiece and tail defects. The motility of the sperm improved to 7 per cent when semen was collected daily but its morphology did not improve. Electron microscopy revealed that the defects consisted mainly of a loss of microtubules in the axoneme and of disorganised midpieces. A pregnancy rate of 24 per cent per cycle and 44 per cent for the season was achieved in 32 mares after the insemination of whole ejaculates collected from the stallion frequently. The fertility was much higher than would have been expected from the characteristics of the semen. It is concluded that this sperm defect, reminiscent of the 'Dag defect' in bulls and the defect in T-locus mice, does not render the animal infertile. PMID- 1858273 TI - Morphology of poxviruses from reptiles. PMID- 1858274 TI - Vets, cats and pain. PMID- 1858275 TI - 'Abortus blauw'. PMID- 1858276 TI - Aggression in golden retrievers. PMID- 1858277 TI - Anthelmintic resistance. PMID- 1858278 TI - Aural haematomata, cauliflower ears and Psoroptes in sheep [corrected]. PMID- 1858279 TI - Distribution of bitches' nipples. PMID- 1858280 TI - Tilmicosin and calf pneumonia. PMID- 1858281 TI - Trypanosoma evansi infection in cattle, buffaloes and horses in Indonesia. AB - Cattle, buffaloes and horses in several areas of Indonesia were examined for evidence of infection with Trypanosoma evansi by the microhaematocrit centrifugation technique (MHCT) and an enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to T. evansi. Evidence of infection was found in animals at each sampling site although differences were seen in prevalence rates between sites. Prevalence rates in buffalo were usually higher than in cattle in the same area while in horses they were much lower than in cattle or buffalo. An age-dependent prevalence rate was seen in buffalo and cattle with the highest rates seen in animals older than 2 years. These results concur with the view that T. evansi infection is widespread throughout most of the livestock-producing areas of Indonesia. The apparent lack of any obvious disease owing to T. evansi infection in the sampled animals suggests that a form of stability exists in most endemic areas which serves to ameliorate the effect of T. evansi infection and has an immunological basis linked to the parasite's limited antigenic diversity. PMID- 1858283 TI - Serum IgG response of Manchego lambs to infections with Haemonchus contortus and preliminary characterization of adult antigens. AB - Manchego lambs (16-18 weeks old) were infected with 2500 infective larvae (L3) of Haemonchus contortus and challenged 2 months later with 5000 L3. The serum IgG anti-Haemonchus response was estimated by enzyme-linked immunosorbent assay (ELISA) using soluble proteins from adults and L3. Previously infected Manchego lambs failed to mount a protective immune response against challenge, at least as assessed by faecal egg counts and pre-patency periods. Primary infection did not provoke any rise in specific anti-parasite serum antibodies, whereas a weak but significant rise was observed in challenged 6.5-month-old lambs which was very similar in both infected and non-infected lambs. The serum IgG anti-parasite response was higher against larval antigens than adult soluble proteins. Preliminary characterization of adult and larval soluble proteins by electrophoresis under reducing and denaturing conditions and Western blotting showed high cross-reactivity of both extracts. Immunoblots of adult H. contortus probed with infected and challenged lambs' sera did not yield conclusive results, although some low molecular weight peptides were recognized. PMID- 1858282 TI - A field evaluation of anthelmintics for control of cyathostomes of horses in Brazil. AB - The anthelmintic efficacy of ivermectin (IVM), piperazine citrate (PPZ) and fenbendazole (FBZ) alone, and combinations of FBZ with varying dosages of PPZ, was evaluated for the control of strongyles of Mangalarga equids. In all cases of positive strongly egg counts per gram of faeces (EPG) before and after treatment, pure populations of cyathostome larvae with eight gut cells were consistently observed in faecal cultures. The faecal egg count reductions (FECR) were evaluated between Day 7 and Day 56 post-treatment. Significant differences (P less than or equal to 0.05) were found between Day 7 and Day 49 when comparing the mean EPG values of IVM with those of the other anthelmintics. PPZ alone and the combination of FBZ (7.5 mg kg-1) and PPZ (55 mg base kg-1) did not show significant differences during the trial; both groups exhibiting an FECR of greater than 90% between Day 7 and Day 30. Horses treated with the combinations of FBZ (7.5 mg kg-1) and PPZ at either 40 or 25 mg base kg-1, and with FBZ alone at either 7.5 or 15 mg kg-1, showed an FECR of less than 90% 2 weeks after treatment. The emergence of a degree of resistance of strongyles to FBZ and PPZ in a segment of the cyathostomes in this population is suggested. PMID- 1858284 TI - Changes in liveweight gain and blood constituents in experimental infection of goats with a goat-derived compared with a sheep-derived strain of Haemonchus contortus. AB - Two groups of goats were experimentally infected with two different strains of Haemonchus contortus and compared with the controls. Group A animals were infected with a goat-derived strain (GDS) while Group B animals were infected with a sheep-derived strain (SDS). Changes in the liveweights and some blood constitutents between the two infected groups were compared. The pathogenic effects of the GDS larvae were generally more serious when compared with those of the SDS larvae. PMID- 1858285 TI - Effects of challenge with trichostrongylid nematode larvae on immunologically resistant grazing yearling sheep in South Australia. AB - Paddocks near Gawler, South Australia, were grazed by newly weaned sheep which received either no anthelmintic treatment, regular 3-weekly treatment or a single treatment in February. A decline in the faecal egg count of untreated sheep in autumn associated with the ingestion of infective larvae indicated that the sheep had developed a resistance to reinfection. At the end of the experiment, 10 sheep were experimentally infected with Trichostrongylus vitrinus larvae to demonstrate this resistance. Untreated sheep grew less wool and had lower body weights when compared with treated animals and were extremely 'daggy'. A single treatment in February did not prevent production losses or scouring. PMID- 1858287 TI - Effect of treatment with netobimin on milk production of sheep. AB - In the Basque country lambing takes place during winter, followed by milking until late spring or summer, so it was considered that this would be the most profitable period for deworming, when there was an increased production pressure on ewes with depressed immune status owing to the peri-parturient relaxation of immunity. The drug employed was netobimin, and the trial was carried out in 22 commercial flocks, in each of which ewes were allocated to one of three similar groups. One group was left as a non-treated control (T0), the second was dosed 15 days before parturition (T1), and the remaining group dosed both at 15 days before and 15 days after lambing (T2). Mean total milk production in the T2 group increased by 8.8 and 6.3% in the second and third month post-partum, respectively, compared with that of the controls (T0), while over the standard lactation period of 120 days the T2 group showed a significant (8.9%) increase in production compared with the controls. The T1 group did not significantly differ from T0. The market value of the increase in milk production was calculated to be approximately 700% of the cost of treatment with netobimin. PMID- 1858286 TI - Pathophysiology of Haemonchus placei infection in calves. AB - This study was conducted to investigate the pathophysiology of Haemonchus placei infection in Friesian calves. Seven calves were divided into two groups, three uninfected calves (control group) and four infected animals. The latter group were infected orally with 500 H. placei larvae kg-1 body weight. Five weeks after infection they were all housed in metabolic crates and injected with 125I-bovine albumin. 51Cr-red cells and 59Fe-transferrin, to study albumin metabolism, erythrokinetics and ferrokinetics. The results showed that there was a significant reduction in the mean haematocrit values and reduced weight gains in the infected calves compared with the controls. There was also a change in the distribution of albumin from the extravascular to the intravascular pool and a significant increase in the plasma and blood volumes of infected calves although the blood and albumin loss via the gastrointestinal tract recorded in this study was similar in both groups. PMID- 1858288 TI - Enhanced resistance to cattle grub infestation (Hypoderma lineatum de Vill.) in calves immunized with purified hypodermin A, B and C plus monophosphoryl lipid A (MPL). AB - The influence of an antigen-specific cellular and humoral immune response, stimulated by immunization, on survival of a challenge infestation of Hypoderma lineatum was investigated. Calves immunized with a purified combination of hypodermin A, B and C plus monophosphoryl lipid A (MPL) developed a strong antigen-specific cellular immune response by completion of the immunization schedule which persisted to 12 weeks post-infestation. Responsiveness of peripheral blood lymphocytes to the mitogens concanavalin A and pokeweed was also elevated at 4 and 12 weeks post-infestation. Western blot analysis at the time of maximum grub counts demonstrated that immunized calves responded to hypodermin A, B and C while those receiving only MPL or infested controls responded only to hypodermin B and C. The antigen-specific antibody response as measured by ELISA at maximum grub count was significantly higher in vaccinated calves than in infested controls while the response in calves receiving only immunostimulator was also significantly elevated. Immunized (antigen plus MPL) calves produced 5.0 +/- 6.9 grubs per animal which successfully pupated while those receiving MPL alone produced 16.4 +/- 6.1 and infested controls produced 32.2 +/- 10.9 grubs per animal. PMID- 1858289 TI - Predation on livestock ticks by chickens. AB - Chickens were shown to be natural predators of ticks. Rhipicephalus appendiculatus were recovered in large numbers from the crops and gizzards of chickens which had scavenged for 30 min-1 h among tick-infested cattle. Other ticks recovered were Amblyomma variegatum and Boophilus decoloratus. The numbers of ticks recovered ranged from 3 to 331, with an average of 81 per chicken. Cattle facilitated the predation of ticks by certain behavioural actions. Chickens also picked up both engorged and unengorged ticks seeded on vegetation, but unengorged ticks were preferred. The possibility of tick predation by chickens forming a viable biological control component in an integrated tick management system in Africa is discussed. PMID- 1858290 TI - Histopathology of attachment sites of Amblyomma variegatum and Rhipicephalus appendiculatus on zebu cattle of varying resistance to ticks. AB - Mature, unimproved East African Zebu cattle (Bos indicus) naturally exposed to ticks from birth were ranked for resistance to ticks by repeated whole-body counts of infesting ticks. Four cattle of high resistance, four of low resistance and two of intermediate resistance were artificially infested with nymphs of Amblyomma variegatum and Rhipicephalus appendiculatus. Two Friesian cattle (Bos taurus) with less exposure to ticks were similarly infested. Biopsies of tick attachment sites were examined histologically. All attachment sites showed acute inflammatory lesions, and sites of both tick species on high resistance cattle showed delayed hypersensitive reactions with intra-epidermal pustulation and significant increases in the numbers of granulocytes. The predominant cells infiltrating attachment sites on high resistance cattle were eosinophils with A. variegatum and neutrophils with R. appendiculatus. Such differences need to be taken into account in developing immunological tests for selecting cattle for resistance but there are sufficient common features of reactions to the two infesting tick species to justify dermal hypersensitivity tests. PMID- 1858291 TI - Isolation and characterization of an immunogen from the louse Polyplax spinulosa. AB - The reaction of Polyplax spinulosa protein components with antigen-specific rat antisera and with five plant lectins is described. In immunoblotting, the antisera from rats infested with the louse P. spinulosa specifically recognized from 7 to 11 antigenic components of louse whole-body homogenates. Affinoblotting analysis with lectins showed that 10 of these components were glycoproteins with different types of glycan structure. Only one immunogenic antigen was isolated using immunoaffinity chromatography with the gammaglobulin fraction of an antigen specific antiserum as immunospecific ligand. Further electrophoretic and immunochemical analyses revealed that it was a glycoprotein with relative molecular weight (RMW) 31 kDa and with high mannose type of oligosaccharide. PMID- 1858292 TI - Lectin binding analysis of Argas polonicus tissue glycoproteins. AB - Proteins of the Malpighian tubules (MT), midgut tissue (MG), salivary glands (SG), internal reproductive organs (RO), epidermis (EP), cerebral ganglion (CG), rectal ampulla (RA) and larval homogenate (LA) of Argas (Argas) polonicus were studied for their antigenicity and lecin affinity using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, lectin affinoblotting and enzyme-linked lectin sorbentassay (ELLSA) techniques. A glycoprotein of 305 kDA was found in all tissues studied. All low molecular weight antigenic proteins recognized by anti-larval immune pigeon serum, except for one of 35 kDA, i.e. the 19-, 21-, 23-, 27-, 34-, and 46- kDa proteins, were shown to be glycoproteins. The glycosylation was shown to be N-linked in all of these antigens, but O-type glycosylation was also demonstrated in the 34-kDa glycoprotein. The correlation between the glycosylation and antigenicity of these proteins is also discussed. PMID- 1858293 TI - Cryptosporidium parvum in cattle, sheep and pigs in Galicia (N.W. Spain). AB - Infection by Cryptosporidium parvum has been detected for the first time in cattle and swine in Galicia (N.W. Spain). The organisms were also found in one of 69 sheep examined. Although in most cases the parasite was found in young diarrhoeic animals, its presence in asymptomatic mature cattle and piglets was also detected. PMID- 1858294 TI - Trypanosoma evansi infection in bovine and buffalo calves in Indonesia. AB - Fifteen bovine and 11 buffalo calves born on different farms in a Trypanosoma evansi-endemic area of West Java were monitored for the presence of T. evansi and T. evansi antibody at monthly intervals until they were 12 months of age. Fifty percent of the bovine and 83% of the buffalo calves sampled in the first month of life were antibody positive. This antibody was considered to be of colostral origin. Antibody developing later in life persisted for up to 12 months and was considered to have arisen in response to T. evansi infection. No protective function could be ascribed to the colostral antibody. PMID- 1858295 TI - Chemoprophylaxis of coccidiosis in lambs with a single oral dose of toltrazuril. AB - The prophylactic efficacy of a single oral dose of toltrazuril against coccidiosis (mixed Eimeria infections) in naturally infected lambs was evaluated in two experiments. Toltrazuril at 20 mg kg-1, given on Day 7 or Day 10 after turnout on pasture, proved to be highly efficacious in preventing clinical coccidiosis under Norwegian conditions. Toltrazuril reduced the oocyst output to very low levels, prevented the development of diarrhoea and improved weight gain during the first 4-5 weeks after treatment. Treatment on Day 7 was superior to treatment on Day 10 with respect to improving weight gain and preventing the development of soft faeces. Lambs treated with toltrazuril on Day 7 seemed to be as immune as untreated lambs to natural reinfections with coccidia later in the grazing season. In one of the experiments, natural infections with the nematode Nematodirus battus produced a coccidiosis-like disease in some lambs simultaneously with the outbreak of coccidiosis. PMID- 1858296 TI - The effects of Tordon 202c exposure on urethan-induced lung adenoma formation in female CD-1 mice. AB - Female CD-1 mice were exposed to Tordon 202c, a herbicide containing 2,4 dichlorophenoxyacetic acid and picloram, in the drinking water for 15 w at concentrations ranging from 0 to 0.3% of the product formulation. After 3 w of the 15-w treatment period, the mice received 1.5 mg/g urethan ip. Pulmonary adenoma production was evaluated 12 w later. Tordon 202c exposure produced a dose dependent increase in tumor number, but had no effect on tumor size. Urethan induced sleeping times which reflected the rate of urethan metabolism or excretion were altered, but a specific dose-related effect which could be correlated with tumor production was not observed. This suggests that Tordon 202c exposure influences adenoma formation by immunological mechanisms rather than by causing indirect effects on urethan metabolism or excretion. PMID- 1858297 TI - Percutaneous in vivo and in vitro absorption of lead. AB - Diffusion tubes were used to measure the degree of in vitro penetration of tetrabutyl lead, lead naphthanate, lead nuolate, lead acetate and lead oxide in excised guinea pig skin and human skin from autopsy. Tetrabutyl lead demonstrated the greatest penetration in skin from both guinea pig and man. Lead nuolate, lead naphthanate and lead acetate followed in descending order in the human tissue. A similar pattern occurred with guinea pig skin in most cases. There were no measurable amounts of lead oxide absorbed in either species. In vivo absorption was measured by applying 300 mg/kg tetrabutyl lead, lead nuolate, lead naphthanate or lead oxide to the shaved backs of guinea pigs for 7 d under occluded wrappings. Tetrabutyl lead was present in tissues in the highest quantities. Lead nuolate was present in greater amounts than lead naphthanate in the liver and kidneys. Lead acetate was the most poorly absorbed with the exception of lead oxide which demonstrated no absorption. PMID- 1858298 TI - Liver lead burden in hunter-killed ducks from the Coeur d'Alene River Valley of northern Idaho. AB - Liver lead burden was evaluated in ducks from an area in northern Idaho contaminated with mining waste and lead shot. Hunter-killed ducks with lead shot in their gizzard had a mean liver lead concentration of 15.18 +/- 2.51 micrograms/g wet-weight (N = 23) and ducks without lead shot had a mean liver lead concentration of 4.21 +/- 0.47 micrograms/g wet-weight (N = 85). The most hazardous source of lead for waterfowl in this area has been thought to be mining waste-contaminated soils and sediments. Three sediment samples had a mean concentration of 4,520 micrograms lead/g wet-weight. PMID- 1858299 TI - Metabolic disposition of 14C-metanil yellow in guinea pigs. AB - The absorption, metabolism and excretion of 14C-metanil yellow was studied in guinea pigs. Following administration of a single po dose of 5 mg dye (7.6 mu Ci)/kg body weight, 83.4% was excreted through urine and feces within 96 h with the majority accounted for in feces. Liver, kidney and spleen did not have marked accumulation of counts, whereas testes and gastrointestinal tract retained 1.9 and 9.7% of the radioactivity, respectively. Analysis of urine and feces detected 2 azo-reduction metabolites of metanil yellow which were characterized by TLC and IR, NMR and mass spectroscopic studies as metanilic acid and p aminodiphenylamine. PMID- 1858300 TI - Distribution of chromium in the internal organs of potassium chromate treated chicks. AB - After exposure of growing chicks to different concentrations of dietary chromium (Cr) as potassium chromate (K2CrO4) for a period of 3 w, the Cr uptake by different internal organs was determined. More Cr was accumulated in the kidney, liver, pancreas and spleen than in the blood, muscle, heart and lung. A very small amount was found in the brains of the birds given different concentrations of Cr. PMID- 1858301 TI - Effects of alpha-1-acid glycoprotein on the cardiovascular toxicity of nortriptyline in a swine model. AB - Tricyclic antidepressant toxicity is a frequently encountered and life threatening problem in emergency medicine. This trial investigated the effect of alpha-1-acid glycoprotein (AAG), an acute phase reactant with a high affinity for basic drugs, on the clinical and pharmacological manifestations of nortriptyline (NT) toxicity. Fourteen pentobarbital-anesthetized swine (10-13 kg) were given a 10-min loading dose followed by a 45-min maintenance infusion of NT to achieve a plasma level of approximately 1000 ng/ml. At the end of the infusion, 7 control (C) animals were given 50 ml of 0.9% saline and 7 AAG animals were given 50 ml of 10% AAG, both over 15 min. Heart rate, QRS duration, QTc interval, blood pressure, temperature, arterial blood gases, albumin, and plasma-free and plasma bound NT levels were measured at baseline and at every hour for 4 h. One death was noted in the AAG group and none in the C group (p = NS). Mean total NT levels after infusion in the C group was 1240 +/- 1118 ng/ml and in the AAG group 804 +/ 194 ng/ml (p = NS). No significant differences were found in the plasma-free fractions between groups at any time interval. However, significantly shorter QTc intervals were found during treatment with AAG compared to controls (P = 0.02). A trend toward increased systolic blood pressure (p = 0.09) and shorter QRS duration (p = 0.09) was noted during AAG treatment. No significant changes were shown between groups with respect to heart rate, arterial blood gases, or albumin measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858302 TI - Effect of glucose treatment on carbohydrate content in various organs in mice after acute As2O3 poisoning. AB - Glucose treatment improved survival and symptoms in mice poisoned with As2O3. In order to get more insight into the mechanisms involved, postmortum changes in glucose and glycogen content of various organs and pathology were investigated in mice acutely poisoned with As2O3 and treated with glucose. Forty mice each received 12.9 mg As2O3/kg sc as a single injection. The first group of 10 mice had no further treatment. Fifteen minutes after the As2O3 injection and every 2 h thereafter, the second group (10 mice) received saline and the third group (10 mice) received 5% glucose ip. Groups 4 and 5 (5 mice each) received either saline or glucose only. The injection volume in all groups was 10 microliters/g mouse. Group 6 (5 mice) had no treatment whatsoever. Immediately after death brain, muscle and kidneys were prepared for the enzymatic determination of glucose and glycogen. Samples of the brain, muscle, kidneys, liver, small intestine, colon and spleen were taken for microscopic examination. Independent of the therapeutic procedure, decreases in the glycogen in livers and increases in fat in livers and muscles were observed in mice which died. All mice which died showed heavy leucocytes disruptions, increased fat, and decreased glycogen in the spleen. Intrafolliculary disruptions of leucocytes in the small intestine and colon, as well as patchy hyperemias and hemorrhagic spots in the papilla of the kidneys, were observed in non-survivor mice. Decreased glucose and glycogen was in the brains of non-survivor mice; no differences in glucose and glycogen were found in brains of the mice which survived.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858304 TI - Drought increases forage nitrate and cyanide. AB - To investigate drought-associated increases in concentrations of nitrate and cyanide in animal forage, we compared forage nitrate and cyanide in 1986-87 (annual rainfall 33 in) to nitrate and cyanide in a drought (1988 and 1989; annual rainfall 20 and 27 in, respectively). Fifteen to 20% of the nitrate and cyanide samples from 1986-1987 had sufficiently high concentrations to be of concern (3000 ppm nitrate, 20 ppm cyanide as submitted). Only 4-6% of the 1986 1987 samples had concentrations sufficiently high to produce acute respiratory distress (13,000 ppm nitrate, 50 ppm cyanide as submitted). During 1988 sample numbers had more than doubled, suggesting increased concern for the possibility of nitrate or cyanide intoxication and yielding parallel increases in the number of samples with elevated nitrates or cyanides. By 1989, 25-33% of the samples had concentrations of health concern with respect to either nitrate or cyanide, while 14-19% had concentrations sufficiently high to produce acute respiratory signs. Shortages of forage caused by a 2-y drought were further exacerbated by nitrate and cyanide increases in that feed. Future efforts should concentrate on controlling groundwater nitrate and delivery of nitrate to the plant root systems. PMID- 1858303 TI - Evaluation of changing patterns in children poisonings and prevention. AB - Poisoning prevention strategies have to be modified according to the risk variations with age and time. Epidemiologic surveillance usefulness was confirmed by studying the 0-15 y-old children in the Trieste area from 1976-1987. Significant differences were observed in children under 5 due to an increase in caustic substance and home detergents poisoning and a decrease in analgesic antipyretics ingestion. This was probably due to the introduction by law in our country of child-resistant containers and to a better awareness by parents. At 10 y-of-age and older, alcohol is the cause of most intoxications and more recently benzodiazepine poisonings have significantly increased. At this age poisoning results from deliberate ingestion in most cases; therefore education should be the main preventive strategy. PMID- 1858305 TI - Acute oral hypoglycemic ingestions. AB - We reviewed the poison center records of 48 consecutive reports of oral hypoglycemic exposure reported to the Rush Poison Control Center between January 1988 and December 1989. The average age of ingestion was 15.0 y (range 1 to 75 y). Twenty-three of the patients (48%) were male, while 25 (52%) were female. Twenty-nine patients ingested glyburide, 10 chlorpropamide, 6 glipizide, 2 tolbutamide, and 1 each for tolazamide and phenformin. One patient ingested both glyburide and tolbutamide. Sixteen cases (33%) involved coingestants. Accidental cause was the primary reason for ingestion in 33 cases (69%) with suicidal intent being mentioned in an additional 11 cases (23%). Thirteen patients (27%) were treated and released from a health care facility, while the same percentage of patients were admitted. There was no adverse effect in 24 patients (50%) while 9 patients (19%) had minor effects without residual disability. Only 2 patients (4%) experienced a major effect. No deaths were reported. We conclude that oral hypoglycemic ingestions generally have a successful outcome and there does not appear to be a significant difference whether a short/long acting agent or first/second-generation product was ingested. PMID- 1858306 TI - Arsenic poisoning in livestock. AB - Arsenic is an important heavy metal intoxicant to livestock. Arsenical pesticides present significant hazards to animal health. The toxicity of arsenic varies with several factors--its chemical form, oxidation states, solubility. The phenylarsonic compounds are the least toxic and are used as feed additives in swine and poultry rations. However, roxarsone has a higher absolute toxicity than arsanilic acid. The mechanism of action is related to its reaction with sulfhydryl groups values to enzyme function and to its ability to uncouple oxydative phosphorylation. Most animals excrete arsenic quite readily. Toxicoses caused by inorganic and aliphatic organic arsenicals result in a different clinical syndrome than that from the phenylarsonic compounds. Arsenic poisoning may be confused with other types of intoxication. The specific antidote for inorganic arsenical poisoning is dimercaprol (BAL). PMID- 1858307 TI - Acute poisoning by lupine seed debittering water. AB - A case of acute poisoning by ingestion of water used to debitter lupineseeds, an exceptional occurrence in human clinics, is reported. The patient showed the anticholinergic syndrome for 48 h, which then subsided spontaneously. PMID- 1858308 TI - Effect of inadequate antivenin stores on the medical treatment of crotalid envenomation. AB - The case of a 27-y-old male with a serious Crotalus atrox envenomation is presented. His medical care was compromised by the lack of readily available polyvalent Crotalidae antivenin. An investigation of antivenin stocking by health care facilities in Arizona was undertaken. Failure to stock sufficient quantities of antivenin to initiate treatment of a single patient with a severe envenomation was found in 43.5% of urban hospitals, 41.2% of rural hospitals within 25 miles of another hospital, 52.9% of rural hospitals greater than 25 miles from another hospital, and 41.7% of Indian Health Service hospitals. Current antivenin stocking was related to antivenin use during the previous year. Reliance on recent antivenin use to guide current antivenin stocking leaves many hospitals with insufficient antivenin stores and may seriously compromise the medical care of patients suffering from rattlesnake envenomations. PMID- 1858309 TI - Exaggerated warfarin sensitivity: a case report. AB - A 64-y-old male was hospitalized because of significant bleeding and a prolonged prothrombin time (PT) (greater than 200 sec) following an inadvertent doubling of his anticoagulant dose. He was previously well controlled on 2.5 mg warfarin every fourth day. Treatment included vitamin K, fresh frozen plasma, and packed red blood cells. Warfarin plasma concentrations, clotting factor analysis (CFA) and PTs were analyzed to evaluate this patient. Following hospitalization, the patient was followed by the Anticoagulation Clinic and his dose was stabilized at 0.5 mg daily. He experienced no further bleeding episodes and his PT ratio was maintained at 1.5 times control. The response to a dose of warfarin varies greatly from patient to patient. Previous reports of abnormal responses to warfarin can be categorized as either warfarin "resistant" or "sensitive." The preponderance of reports are compliance or hereditary warfarin resistance. This patient represents a case of exaggerated warfarin sensitivity that cannot be easily explained. There was no evidence of a drug interaction, warfarin concentrations were not excessive, and CFA was reflective of a moderate warfarin effect. Extreme tissue sensitivity to warfarin is a plausible explanation for this abnormal response. PMID- 1858310 TI - Forensic toxicology and insects: a minireview. AB - In cases of suspicious death, various postmortem changes and the insect species infesting the corpse have been employed to compute the time of death. Recently, chemical analysis of the life stages of insects infesting the corpse has revealed poisons and drugs consumed for suicide in the body of the deceased. This new area can provide proof of the cause of death. It is recommended that whether or not there is suitable tissue samples for the analysis, the developmental stages of insects thriving on the carcass should always be collected as exhibits for analysis. PMID- 1858311 TI - Peganum harmala L: a poisonous plant of North Africa. PMID- 1858312 TI - An outbreak of Vicia villosa (hairy vetch) poisoning in grazing Aberdeen Angus bulls in Argentina. AB - Vicia villosa (hairy vetch) is used as a forage source in some cattle-producing areas in Argentina. The plant had no previous reports of toxicity in this country. A herd of 33 Aberdeen Angus bulls grazed during 20 days in October on a pasture composed mainly of hairy vetch. Eight animals developed conjunctivitis, rinitis, dermatitis, loss of hair and fever. All of them died within 15 d after the development of signs with a marked loss of body condition. No more animals became sick 5 d after the removal of the herd from the pasture. Serum parameters tested (calcium, phosphorus, magnesium, GOT, alfa-GT and bilirubin) enlarged liver and spleen, generalized hemorrhage in the abomasum, dilated kidneys and multiple pale areas on the heart. Severe necrotizing granulomatous myocarditis, interstitial nephritis, and necrotizing cholangitis were the most striking microscopic changes. Close observation of animals feeding on pastures in which V villosa is dominant is the only prevention. PMID- 1858313 TI - An investigation of metal concentrations in blood of industrial workers. AB - Pigments may contain chromates of zinc and lead, dioxide of manganese, oxides of copper and cobalt, and sulphides of cadmium. Workers engaged in the production of colored glass articles are exposed to fumes and dusts from these pigments. Exposure to these metals through inhalation may lead to a high concentration of these metals in blood. Correlations between biometric characteristics of workers and the blood levels of metals, and between blood levels of different metals were explored. Blood copper and chromium were correlated with occupational history. Significant correlations between blood levels of lead, copper, chromium and manganese were also observed. PMID- 1858314 TI - Snake venom or antivenom induced urticaria. AB - An amateur herpetologist developed chills, diaphoresis and generalized urticaria 5 h after receiving Antivenin (Crotalidae) Polyvalent (Wyeth) for treatment of rattlesnake (Crotalus atrox) envenomation. The patient had been bitten 8 mo earlier by a copperhead (Agkistrodon contortrix mokeson) resulting in minimal envenomation. He also had been skin testing himself for 6 mo with both diluted Crotalus atrox venom and Antivenin (Crotalidae) Polyvalent (Wyeth) to determine how sensitive he was to antivenom and how resistant he was to the effects of venom. Unusual reactions to antivenom during the treatment of snake-bite victims, such as amateur herpetologists or snake fanciers, with access to both venom and antivenom should raise questions about unusual means of sensitization. PMID- 1858315 TI - Novel occurrence of cyclopiazonic acid in sunflower seeds. AB - Cyclopiazonic acid (CPA), a secondary metabolite produced by several species of Aspergillus and Penicillium, was detected in moldy sunflower seed screenings fed to sows who experienced conception problems and feed refusal. Tandem mass spectrometry confirmed the CPA which was estimated by thin-layer chromatography (TLC) to be present at 10 ppm. A Penicillium species was isolated from the moldy seeds, but in culture it did not produce CPA. PMID- 1858316 TI - The identification of hepatotoxic pyrrolizidine alkaloid exposure in horses by the demonstration of sulphur-bound pyrrolic metabolites on their hemoglobin. PMID- 1858317 TI - Polarity specific adaptation to motion in the human visual system. AB - Three experiments investigated polarity specific adaptation to movement. Experiment 1 tested for temporal polarity specific adaptation, using counterphase sawtooth gratings as adapting and test stimuli. Each counterphase grating contained oppositely moving sawtooth components, and was thus balanced for direction, but both components of the adapting grating created only one polarity of luminance change over time, whereas the components of the test grating presented different signs. After adaptation, only the test component containing the unadapted temporal change was visible. A second experiment, using an analogous procedure, found evidence for spatial polarity specific adaptation. Experimental results can be explained by motion detectors which preserve information about spatial and temporal polarity. A third experiment found that spatial and temporal polarity specific adaptation differ in their dependence on temporal frequency. PMID- 1858318 TI - Foveal cone detection statistics in color-normals and dichromats. AB - We measured for six male observers, the psychometric functions for the detection of two simultaneously presented points of light. The test stimuli were two 1 min point sources separated by 17 min arc, and pulsed for 0.5 msec. The stimuli varied in wavelength from 500 to 620 nm. The psychometric functions were fit with a model that assumes ideal detection and the following properties: (1) Poisson distributed quantal absorptions; (2) binomial sampling of foveal long-wavelength sensitive (LWS) and middle-wavelength-sensitive (MWS) cones; (3) independent responses of the LWS and MWS cones; and (4) the Smith-Pokorny fundamentals for cone spectral sensitivities. Based on chi 2 fits to the psychometric functions for detecting neither, one or both of the two-point stimuli presented, estimates were derived for the minimum quantal catch by a single cone for detection (C), the number of effective cones illuminated by a point stimulus at threshold (N) and the proportion of central foveal cones of the LWS type (PL). Three observers were color-normal, two were protanopes and one was a deuteranope. A second deuteranope was included in the design but his data were too unreliable for an unambiguous solution. The estimated quantal requirement C was consistently near 5(4-6), and the effective number of illuminated cones always was 1 or 2. The plausible range of PL (98% confidence interval) for the color-normal observers was 0.48-0.68 (observer YY), 0.76-0.90 (observer MW) and 0.77-0.95 (observer DF). The best fitting PL solution for these observers were 0.61, 0.82 and 0.88, respectively. These were comparable to the values obtained from flicker photometric data. The best PL value for each of the protanopes was 0.00 and for the deuteranope the best PL value was 0.98. PMID- 1858319 TI - Conditions for the detection of coherent motion. AB - Previous studies have suggested that human motion perception involves at least two different detection stages: an orientation selective or component motion stage and a combination stage where selectivity to the coherent motion of a pattern, e.g. a plaid is established. These studies are inconclusive as to the motion detection process per se. Here we provide evidence that the motion detectors involved are of the correlation type. We determined critical values for the temporal and spatial modulation of the stimulus structure where the motion of the stimulus is no longer visible. Our results indicate that the spatial parameters of plaid- and component-motion detectors are identical but that the critical temporal modulation period is shorter for plaid-motion detectors. The results are discussed with respect to recent neurophysiological and psychophysical evidence for the two-stage motion detection model. PMID- 1858320 TI - Nonadditivity of masking by narrow-band noises. AB - Characterization of the visual system as a linear system has many consequences. One property implied by such a characterization is that signal-to-noise ratio at threshold is constant, so that the contrast energy of a sinusoidal grating at threshold depends on the effective noise passed by the filter used to detect the target. When the contrast energy in an external noise is sufficiently high, the contribution of internal noise may be conveniently ignored. In such circumstances, the effectiveness of a given noise is measured by its ability to mask the target. One consequence of the linearity assumption is that if the energy of the effective noise is increased by a factor k, then threshold energy of the signal is increased by the same amount. The contrast energy at threshold in the presence of a masker created by adding two maskers should be the sum of the threshold energies in the individual maskers. We have tested this hypothesis for spectrally nonoverlapping maskers. We find that the contrast energy required to detect the target in the presence of the combined maskers is much greater than the sum of the threshold energies for the two maskers. This "excess masking" violates the linearity assumption. On the other hand, when maskers do have spectral overlap, no excess masking is found. PMID- 1858321 TI - A model for perceived spatial frequency and spatial frequency discrimination. AB - The responses of labelled spatial frequency channels are combined to generate an index of perceived spatial frequency. Spatial frequency discrimination thresholds are shown to be inversely related to the slope of the function of the index vs spatial frequency, when it is plotted on log-log co-ordinates. PMID- 1858322 TI - Texture segmentation and pop-out from orientation contrast. AB - In arrays of oriented lines, a target at a different orientation is effortlessly detected; it "pops out" from the pattern. Similarly, textures with line arrays at different orientations seem to dissect into separate areas with the spontaneous percept of distinct borders between them. In recent models, these perceptual phenomena were linked to the pre-attentive detection of certain features and of first-order differences in their spatial distribution. In contrast, however, psychophysical experiments show that texture segmentation and visual pop-out arise from orientation differences rather than from the orientation features themselves, a view which is supported by neurophysiological data from the monkey visual cortex. PMID- 1858323 TI - Effects of background illumination on cat horizontal cell responses. AB - The process of light adaptation in cat horizontal cells was studied by means of intracellular recordings in the optically intact, in situ eye. Response vs intensity profiles were measured using increment- as well as decrement-flashes of "white light" on steady backgrounds. The effects of background illumination in the mesopic and photopic range on both purely rod-driven horizontal cells and mixed rod and cone input horizontal cells were investigated. Increasing the background illumination for mixed-input horizontal cells strongly reduced the contribution from the rod system. The rod aftereffect in the responses to high intensity flashes is totally suppressed at higher background levels. Light adaptation resulted in a sustained hyperpolarization without a substantial effect on the total response range of the response vs intensity curve. At higher background intensities more of the response range is made up of depolarizing responses to decrements of light. Increasing the background illumination also shifted the operating curve to higher intensities. Increment threshold functions, measured with a 3.9 deg diameter test spot on a large background (8.8 deg diameter) showed a linear relation between log threshold intensity and log background intensity with a slope of, on average, 0.64. The response vs intensity curve for the rod horizontal cell typically spanned a narrower intensity range and was displaced toward lower intensities as compared to that for the mixed input horizontal cells. Background illumination greatly reduced the total response range for rod horizontal cells. Increment threshold curves for rod horizontal cells clearly indicated loss in sensitivity due to response compression. PMID- 1858324 TI - Inhibitory refinement of spatial frequency selectivity in single cells of the cat striate cortex. AB - Single cells in the cat striate cortex are more selective for the spatial frequency of sinewave grating stimuli than are cells of the retina or lateral geniculate nucleus. We have explored the possibility that this enhancement of selectivity results from spatial-frequency-selective inhibition. Stimulation with two superimposed gratings, one to excite the cell and one to prove for inhibition, revealed spatial frequency-dependent response suppression in 74% of the total population studied. Suppression was slightly more prevalent in simple cells (80%) than in complex cells (68%). In 93% of the cases where suppression was found, its tuning was complementary to excitatory spatial frequency tuning, and the strongest suppression was usually found where the excitatory tuning function approached zero imp./sec. Characteristics of the phenomenon were independent of cortical layers. We conclude that organized inhibitory mechanisms serve to refine the spatial frequency bandpass of striate cortical cells. This provides evidence for another degree of nonlinearity in the organization of cortical receptive fields and supports the hypothesis that a fundamental function of the visual cortex is image dissection in the domain of spatial frequency. PMID- 1858325 TI - The gecko visual pigment: the anion hypsochromic effect. AB - The 521-pigment in the retina of the Tokay gecko (Gekko gekko) readily responds to particular physical and chemical changes in its environment. When solubilized in chloride deficient state the addition of Class I anions (Cl-, Br-) induces a bathochromic shift of the absorption spectrum. Class II anions (NO3-, IO3-, N3-, OCN-, SCN-, SeCN-, N(CN)2-), which exhibit ambidental properties, cause an hypsochromic shift. Class III anions (F-, I-, NO2-, CN-, AsO3-, SO2(4-), S2O2(3-) have no spectral effect on the 521-pigment. Cations appear to have no influence on the pigment absorption and Class I anions prevent or reverse the hypsochromic shift caused by Class II anions. It is suggested that the spectral displacements reflect specific changes in the opsin conformation, which alter the immediate (dipolar) environment of the retinal chromophore. The protein conformation seems to promote excited-state processes most in the native 521-pigment state and least in the presence of Class II anions. This in turn suggests that the photosensitivity of the 521-pigment is controlled by the excited rather than by the ground-state properties of the pigment. PMID- 1858326 TI - Color in visual search. AB - Colored targets pop out of displays under conditions in which the standard red green, yellow-blue and black-white mechanisms cannot directly mediate detection. Experimental evidence suggests that observers possess chromatic detection mechanisms tuned to intermediate hues such as orange as well as to hues characterizing the standard color-opponent mechanisms and that these mechanisms, as a group, form a fine-grained representation of hue within the central visual field. Spatially-parallel search is mediated by a single such mechanism that is spectrally sensitive to the target chromaticity but insensitive to the distractor chromaticities; different mechanisms are used to detect a single target in a way that depends on distractor chromaticities. PMID- 1858327 TI - Model of peripheral and amblyopic hyperacuity. AB - Vernier thresholds rise much more rapidly in the periphery than do grating thresholds. A similar dissociation between acuity and hyperacuity has been shown to be present in strabismic but not in anisometropic amblyopia, thus leading to the suggestion that the strabismic fovea is similar to the normal periphery. Here it is shown that a quantitative model for spatial pattern discrimination, which accounts for foveal hyperacuity data, can be extended to encompass both the periphery and amblyopia if appropriate alterations are made. For the periphery it is necessary to increase the size of model receptive fields and to introduce both spatial undersampling and position irregularity (i.e. irregularity in the location of cortical filters). The strabismic fovea also requires spatial undersampling and position irregularity but no change in receptive field size. Defects in the good eye of strabismics can be explained by spatial irregularity. Finally, the anisometropic fovea requires a reduction in mechanism sensitivity but neither spatial undersampling nor position irregularity. PMID- 1858328 TI - A transducer model for contrast perception. AB - Multiple channel models of visual function proposed to date have been either threshold models or suprathreshold models. The transition between detection and perception of contrast which involves the gradual disappearance of spatial response pooling has not been addressed. We propose a model that allows us to simulate contrast detection, contrast perception and the gradual disappearance of spatial response pooling with contrast. The model successfully predicts thresholds and perceived contrast functions for several multiple component stimuli. PMID- 1858329 TI - Contribution of transient and sustained responses to the perception of apparent motion. AB - The likelihood of seeing apparent motion (AM) was measured as a function of inter stimulus-interval (ISI) between two isolated Gabor patches separated by 4 deg with spatial frequency (0.75, 2.0 and 4.5 c/deg) and exposure duration (33 and 1000 msec) as parameters. For the short stimuli, the likelihood of AM for the low spatial-frequency of 0.75 c/deg was higher than that for the high-spatial frequency of 4.5 c/deg, but for the long stimuli, the former was similar to, or lower than the latter. Decreasing the mean luminance from 190 to 0.8 cd/m2 impaired AM for the short stimuli of 2.0 c/deg, but improved AM for the long stimuli. The dependencies of AM on spatial frequency, exposure duration and adaptation level may be ascribed to the changing contribution of the transient and the sustained responses. PMID- 1858331 TI - [Strength of nucleic acid-protein interactions and synthesis of nucleic acids and proteins in the cell]. AB - Nucleoprotein-celite chromatography of cultivated cells nuclei, where incorporation of 3H-thymidine, 3H-UTP and 14C-aminohydrolysate into the cells was studied, enabled to detect that lowering of DNA-protein interactions in intact cells occurred simultaneously with a decrease in the rate of spontaneous macromolecular synthesis. The natural growth-regulating drugs, which inhibited distinctly DNA synthesis, inhibited RNA synthesis only slightly and stimulated protein synthesis within the first hours of the cells cultivation, prevented a decrease in tightness of DNA-protein bonds at the beginning of cultivation and then contributed to the reaction thus correlating with inhibition of RNA and protein synthesis. Definite interrelationship was found between alterations in the chromatin structural state and the cells functional activity. The cells lost their functional activity after pronounced decrease in tightness of DNA-protein bonds. PMID- 1858330 TI - [The effect of thyroid hormones on DNA methylation in rat liver in vivo and in vitro]. AB - Methylation of rat liver DNA was studied in vivo and in vitro in presence of various content of thyroid hormones. Both administration of triiodothyronine into intact rats and thyroidectomy led to considerable alterations in activity of endogenous DNA-methylases and in content of m5C in DNA although distinct correlation between these two factors was not detected. Alterations in the acceptor activity of endogenous DNA towards bacterial DNA-methylases of thy Mbu type demonstrated the processes occurring in vivo. The methylase probe 5'...GGA...3' proved to be the universal means for testing of all the types of thyroid status involving either free DNA or whole nuclei. PMID- 1858332 TI - [The effect of gamma-hydroxybutyric acid on the reaction rate of phosphate containing metabolites in the rat brain during ischemia estimated from (31)P-NMR spectroscopic data]. AB - Protective effects of gamma-hydroxybutyric acid on bioenergetic reactions were studied in brain of rats with ischemia using 31P-NMR spectroscopy in vivo. Intraperitoneal preadministration of gamma-hydroxybutyric acid at a dose of 400 mg/kg within 30-40 min before ischemia led to a decrease in the ATP pool in ischemic brain tissue, to alteration in the PCr/ATP ratio in the 31P-NMR spectrum, to prevention of Pi concentration increase and to increase in the intracellular acidosis development rate. Possible mechanisms of the gamma hydroxybutyric acid effects on bioenergetic reactions in nervous tissue during ischemia are discussed. PMID- 1858333 TI - [Function of the pentosephosphate pathway in the rat brain during one-time administration of various doses of ethanol]. AB - A rate of alterations in the enzymatic activity of pentosephosphate pathway and content of glucose in rat brain depended on a dose of administered ethanol. The alcohol inhibitory effect on the enzymatic activity was localized mainly in the brain steam. Impairment of the pentosephosphate pathway functions in alcohol intoxication demonstrated the pathway importance in realization of ethanol effects in nervous tissue. PMID- 1858334 TI - [Middle-molecular peptides in blood as endogenous regulators of lipid peroxidation in the normal state and during thermal burns]. AB - Influence of middle mass peptides upon red blood cell membrane lipid peroxidation was studied in the cells irradiated by ultraviolet in vitro as well as content of the lipid peroxidation products was estimated in mice tissues after intravenous administration of the peptide fraction. Dissimilar effects of the middle mass peptides in vivo and in vitro and role of these peptides in regulation of lipid peroxidation under conditions of burns are discussed. Negative correlation was found between content of middle mass peptides and products of lipid peroxidation in healthy volunteers. PMID- 1858335 TI - [Analysis of changes in serotonin, histamine, and prostaglandin E2 levels in cerebrospinal fluid and body tissues during hyperthermia of various origins]. AB - Physical hyperthermia caused distinct increase in content of serotonin in liquor and its decrease in hypothalamus of rabbits and rats, while histamine and PGE2 were unaltered in liquor of these animals. Considerable increase of PGE2 in liquor simultaneously with unaltered content of serotonin and histamine were detected in rabbits with pyrogenal-caused fever. A decrease in PGE2 content and elevation of serotonin were found in animals liquor after normalization of body temperature within 7 hrs of the pyrogenal treatment. The biogenic amines studied appear to serve as constituents of the natural antipyretic body system in animals, whereas PGE2 belongs to factors responsible for elevation of body temperature. PMID- 1858336 TI - [Change in the lipid composition of the inner mitochondrial membranes in rat organs during adaptation to heat]. AB - Under conditions of adaptation to heating lipid composition in mitochondrial membranes of rat inner tissues was altered as follows: an increase in relative concentration of plasmalogenous forms of phospholipids (kidney, heart) and in content of saturated fatty acids (liver tissue), a decrease in the index of fatty acids unsaturation and in the ratio of fatty acids omega-3/omega-6. The alterations observed enabled the membranes to keep sufficient amount of liquidity essential for functional activity of mitochondria in heating. PMID- 1858337 TI - [Enzyme system for dismutation of active forms of oxygen in the liver during chronic impairment of the hepatobiliary system]. AB - A decrease in activity of main enzymes responsible for inactivation of reactive intermediates of oxygen was found in patients with chronic impairments of liver tissue. In chronic active hepatitis superoxide dismutase and catalase activities were decreased, while more pronounced alterations in the enzymatic activity were observed in primary biliary cirrhosis. Alterations in the rate of antioxidation enzymes activity correlated with severity of pathological process: less distinct alterations in superoxide dismutase and catalase activities were detected in adipose degeneration of liver tissue as compared with those in active chronic hepatitis, and, especially, in primary biliary cirrhosis. The data obtained by means of correlation analysis suggest that interrelationship of the antioxidation system components was deteriorated. The decrease in activity of these enzymes appears to be related to destructive alterations developed in chronic impairments of liver tissue. PMID- 1858338 TI - [Biotransformation and toxicity of xenobiotics in various routes of administration of vitamin A into the rat body]. AB - Deficiency of vitamin A in rats caused a decrease in metabolic rate of acetanilide as well as in elimination of voltaren from blood plasma, while excess of the vitamin (3,000 IU/kg) stimulated voltaren elimination and increased excretion with urine of aminophenol conjugates of acetanilide with sulfuric and glucuronic acids. Under conditions of vitamin A deficiency formation of acetanilide toxic metabolites was increased as a result of which excretion of mercapturic acids with urine was elevated but excess of vitamin A and its hyperdose inhibited these reactions. At the same time, deficiency of vitamin A amplified the paracetamol and voltaren toxicity and its excess exhibited protective effects. PMID- 1858339 TI - [Study of a series of enzyme systems and ultrastructure of rat liver in iron manganese poisoning]. AB - During consumption of drinking water containing manganese or combination of iron and manganese several biochemical patterns were altered in animal blood and liver tissue: content of SH-groups, total lipids, activity of alkaline phosphatase, content of cytochromes b5 and P-450 in liver microsomal fractions. Light and electron microscopy showed that local unspecific alterations of hepatocytes structure occurred in liver tissue. Activation of cytochromes in response to administration of the metals appears to involve alterations in phospholipid composition of endoplasmic reticulum. PMID- 1858340 TI - [Production of a fibrinogen concentrate from small amounts of human autologous blood plasma and its short-term characteristics]. AB - Simple procedure was developed for production of fibrinogen concentrate from small amounts of human autogenous blood using precipitation with polyethylene glycol and ammonium sulfate. Maximal yield of fibrinogen was obtained using polyethylene glycol 2,000 and 6,000 daltons at concentrations 7% and 4.5%, respectively. The fibrinogen preparations included fibronectin, inhibitors of proteinases, factor XIII of blood coagulation, plasminogen. Sigma-Aminocapronic acid and contrical should be added during bloodletting as well as into blood plasma before isolation of fibrinogen to avoid possible fibrinogen proteolysis. PMID- 1858341 TI - [The effect of vitamin A on the glycoprotein fraction composition of rat plasma]. AB - Content of main glycoprotein fractions was studied in rat blood plasma under conditions of vitamin A avitaminosis and of subnormal consumption of the vitamin. Main protein fractions were estimated simultaneously with relative content of glycoproteins which was calculated per mg of total proteins. Relative content of gamma-glycoproteins was increased in avitaminosis A, which appears to occur due to elevation of gamma-globulin synthesis in response to secondary infection or intoxication, while the level of alpha 1- and alpha 2-glycoproteins was decreased simultaneously as a result of possible impairment of protein glycosylation in liver tissue. Subnormal consumption of retinol did not alter content of many protein fractions in blood, however under these conditions absolute content of alpha 1-, alpha 2- and beta 2-glycoproteins as well as relative content of alpha 2-glycoproteins were decreased, thus leading to increase in relative content of underglycosylated proteins in blood. Vitamin A appears to be essential for biosynthesis of individual but not of total blood glycoproteins. PMID- 1858342 TI - [The significance of disruption of erythrocyte membrane protein and lipid composition on the development of a decrease in blood flow properties under extreme conditions]. AB - Protein and lipid composition of erythrocyte membranes as well as loss of erythrocyte filtrability were studied in two experimental models: staphylococcal toxicosis and post-ischemic syndrome. Lipid spectrum of erythrocytes was studied in 16 experiments, protein composition--in 28 experiments and deformation of erythrocytes--in 46 experiments. Considerable destruction of erythrocyte membrane protein moiety and of lipid composition were found under extreme conditions involving distinct loss of phospholipid bilayer and decrease in content of main high molecular proteins. These impairments of erythrocyte membranes and a decrease in erythrocyte flow properties may be referred as principal reasons for development of microcirculation disturbance and of microvascular channel blockade. The alterations observed appear to be responsible for occurrence of components with various ability to aggregation in body fluid media as well as for development of disseminated intravascular coagulation in microcirculation. PMID- 1858344 TI - [Changes in kinetics of deaminated biogenic amines in spontaneous hypertension]. AB - Rate of serotonin and benzylamine deamination was increased in liver tissue of rats with spontaneous hypertension. The increase was due to elevation in Vmax value for monoamine oxidases of the A and B types as compared with the corresponding values of control animals. The Vmax value was increased in kidney of hypertensive animals for MAO of the B type (benzylamine as a substrate). At the same time, Km for MAO of the B type was increased in liver tissue, while Km for MAO of the A type was decreased in brain of hypertensive animals. Titration of the MAO active sites exhibited their increased concentration in the B type MAO in liver mitochondria of experimental animals. The data obtained suggest an important role of alterations in the MAO catalytic activity in pathogenesis of spontaneous hypertension. PMID- 1858343 TI - [The effect of UV-radiation on the metabolic activity of human blood granulocytes]. AB - Influence of UV irradiation (254 nm) on chemoluminescence of blood granulocytes was studied in patients with chronic unspecific lung impairments. Chemoluminescence of leukocytes was decreased after blood irradiation at the rate 10 J/ml as well as after the first course of the UV irradiated blood transfusion. At the same time, high dissimilarity of reactions to the irradiation was found in individual patients: in patients with low initial parameters of metabolism a stable decrease of chemoluminescence was observed to the 2nd, 3d and 4th courses of the irradiation, while in patients with high parameters--only to the 2nd course. This suggests that functional activity of phagocytes may be altered due to UV irradiation effects. PMID- 1858345 TI - [Participation of opioid peptides in regulating the biosynthesis of myocardial protein during stress and adaptation]. AB - After adaptation of rats to extreme conditions treatment of the animals with dalargin (Leu-enkephalin derivative resistant to enzymatic hydrolysis) caused a decrease of catabolism rate in myocardium under stress conditions. Involvement of endogenous opioid peptides in formation of "structure track" during body adaptation to extreme conditions is discussed. PMID- 1858346 TI - [Kinetic properties of lipoamide dehydrogenase of the oxoglutarate dehydrogenase complex of the human heart]. AB - Kinetics of lipoamide dehydrogenase catalyzed reaction is described by Michaelis Menten equation if concentrations of NAD and dihydrolipoamide (DLA) varied. Effective Km values were equal to 0.11 mM for NAD and 0.50 mM for DLA, respectively. Kinetic indications of positive cooperation between sites binding both NAD and DLA were manifested in presence of NADH. Apparent Ki value for NADH constituted 0.88-0.10 mM, thus demonstrating the effective regulation of the lipoamide dehydrogenase activity by end products. PMID- 1858347 TI - [Physiological changes in pyridinoline excretion in urine depending on age and sex]. AB - Natural physiological alterations in excretion of pyridoline (total hydroxypyridoline and lysyl pyridoline) with urine were studied in children and adults depending on age (1-86 years old) and sex. Age-dependent alterations of pyridoline excretion with urine had apparently four phases: an increase, a decrease, stabilization and secondary increase. Distinct dissimilarity between men and women in the rate of pyridoline excretion was found only in the age group of 16-21 years old. PMID- 1858348 TI - [The status of free radical processes in the pulmonary surfactant system in chronic bronchitis patients]. AB - Lipid peroxidation-antioxidants were studied in condensed expired air of patients with chronic bronchitis. Under conditions of bronchopulmonary system impairment considerable activation of lipid peroxidation occurred in surface-active lung layers. These processes were elevated during development of the bronchial obstruction syndrome. Alterations of lipid peroxidation were amplified in patients with chronic bronchitis as functional impairments of the respiratory system increased. The antiradical defense system of lung surfactant was found to correlate inversely with the disease duration and severity of respiratory insufficiency. PMID- 1858349 TI - [A mathematical model of apolipoprotein B metabolism in human blood plasma]. AB - Mathematical model was developed for transport of apo B in blood plasma, which allowed to estimate constants of metabolism of lipoproteins containing apo B, considering the alterations of apo B concentration in circulation followed by immuno- or hemosorption. Some cases were detected where stimulating effect of these procedures on the rate of apo B entering into circulation was found as well as definite ratios were shown between the constants using the parameters of alterations in apo B concentration after elimination of lipoproteins containing apo B from blood plasma. Existence of cases was predicted where fluctuations in apo B concentration attenuated after immuno- and hemosorption which were difficult to find in experiments. PMID- 1858350 TI - [The presence of antithiamine factor--thiaminase--in organs of random-bred albino rats and mice]. AB - Thiaminase activity was not found in rat and mice tissues (liver, kidney tissues) using radiometric procedure. Intact exogenous thiaminase I from bivalve freshwater mollusks was effectively detected in homogenates of rat or mice liver and kidney tissues within 6 hrs after the enzyme parenteral administration into these animals; at the same time, considerable amount of 14C-thiazol developed after thiaminase catalysis was estimated in urine. PMID- 1858351 TI - [A modified method for spectrophotometry determination of monoamine oxidase activity with benzylamine as the substrate]. AB - Modified assay of MAO activity with benzylamine as a substrate is described. The method is based on trapping benzaldehyde product of MAO-reaction by semicarbazide, introduced in samples in 0.6 N perchloric acid after the incubation period. Advantages and disadvantages of semicarbazide presence in incubation medium are discussed. Additional control containing 10(-3) mol/L semicarbazide was required during incubation. PMID- 1858352 TI - [The sensitivity of a number of cell cultures to different types of influenza viruses and their reassortants]. AB - The study of reproductive activity of human and animal influenza A, B, and C viruses as well as influenza A virus reassortants in some cell cultures allowed one to determine the range of cells susceptible for each type (subtype) of the viruses. Differences in the range of cells were demonstrated for different strains of influenza viruses of the same antigenic subtype. It was noted that reassortants of influenza A viruses with the same hemagglutinin subtypes as the parental strains had a wider range of susceptible cell lines and a higher reproductive capacity in these cells. PMID- 1858353 TI - [Experimental phytotherapy of tick-borne encephalitis]. AB - The virucidal effect of aqueous extracts of a number of plants was studied in tick-borne encephalitis (TBE) virus titration in SPEV cell culture in microplates, as well as their capacity to induce resistance in virus-infected mice. The aqueous extracts of ledum, motherwort, celandine, black currant, cowberry and bilberry inactivated TBE virus practically completely, and those of St. John's wort, pot marigold, tansy, chamomile, milfoil, and inula only partially. Studied in vivo, the extracts of motherwort, ledum, tansy and black currant induced resistance of mice to TBE virus infection assessed by the increased survival rate of the animals and significant prolongation of the average longevity. The degree of antiviral activity depended on the preparations used and the routes of their administration. PMID- 1858354 TI - [The process of the pH-dependent fusion of the tick-borne encephalitis virus with artificial membranes]. AB - Fusion of TBE virus with liposomes was distinctly determined at pH 7.0 or lower, the maximum degree of fusion being observed at pH 6.4. Disorders in the native structure of TBE virus envelope protein E prevented virus-membrane fusion. Pre incubation of viral preparations at pH 6.0 completely inhibited the fusion process, while rupture of disulfide bonds in protein E reduced the degree of fusion approximately 2-fold. Reduction of TBE virus infectivity upon changes in the native conformation of protein E as a consequence of disorders in the process of fusion of virions with cell membranes is discussed. PMID- 1858355 TI - [Experimental herpetic infection of the CNS with predominant involvement of the spinal cord]. AB - Clinical, morphological, and virological characteristics of a model of herpes infection of the CNS with predominant involvement of the spinal cord, an acute ascending myelitis with primary demyelinization, are presented. The development of spinal cord lesions after HSV inoculation into the spleen was observed in different species of laboratory animals: mice, hamsters, guinea pigs, and rabbits; some animals (30%-70%) developed generalized infection with the involvement of the brain. The frequency of the spinal cord involvement was found to depend on the age of the animal and the dose of the virus-containing inoculum. Differences in the clinical and morphological manifestations of herpes infection were due to different mechanisms of herpes simplex virus spread in the body: either centripetally on the axons of the visceral nerves innervating the spleen into the thoracal cord, or hematogenic disseminations with virus penetration across the hematoencephalic barrier. The total duration of the disease was 3-12 days depending on the animal species. PMID- 1858357 TI - [The isolation of the morbilli virus from the Baikal seal Phoca sibirica and its preliminary characterization]. AB - A morbillivirus was isolated from the organs of a seal (Phoca sibirica) which had died during 1987-1988 epizootic in Baikal. This Baikal seal morbillivirus (BSM) was adapted to Vero cell cultures in which it induced a cytopathic effect developing to complete destruction of the monolayer. Typing of BSM was done by indirect immunofluorescence test and enzyme immunoassay using antibodies to distemper and measles viruses. A method for virus concentration and purification was developed. According to electron microscopic examinations, the virus virions were spherical particles of heterogeneous sizes over 100 nm in diameter. The clinical picture of seal infection, pathological anatomy and histopathology are described. A possible role of BSM in the epizootics of Baikal seals is discussed. PMID- 1858356 TI - [The therapeutic efficacy of ribamidil and virazole in experimental Lassa fever in monkeys]. AB - The therapeutic efficacy of ribamydil and virasol was evaluated in experimental Lassa fever in monkeys which received these drugs at various intervals after the onset of the clinical illness. Ribamydil or virasol administered in the first day of fever protected from death 60% to 66% of the infected animals, but when the drugs were given 2 days after the onset of fever the number of survivors declined to 0.20%. When the treatment was started 4 days after the onset of fever none of the drugs prevented deaths of Lassa virus-infected baboons. PMID- 1858358 TI - [A comparative study of the paramyxoviruses of birds isolated in the USSR in 1986]. PMID- 1858359 TI - [The reproduction of the tick-borne encephalitis virus in human leukocytes]. PMID- 1858360 TI - [Class-M antibodies to the nuclear antigen in chronic hepatitis B: their significance for the late prognosis]. PMID- 1858361 TI - [A comparative study of monoclonal and monospecific antibodies in determining the immunodominant antigenic sites of influenza virus A (H3N2) hemagglutinin]. AB - Comparative studies of monospecific (MSA) and monoclonal (MCA) antibodies showed MSA to detect three non-overlapping immunodominant sites on the surface of hemagglutinin (HA) molecule whereas MCA established more subtle differences in HA antigenic structure on the level of epitopes with different immunological significance. The activity of MSA and MCA differed in various tests. While MCA were more active in HI and EIA tests, MSA had a higher neutralizing activity, reducing the infectious virus titre by 5.0-7.5 Ig. Similar reduction of the virus biologic activity was observed only with two MCA whereas the other 20 MCA had a poor neutralizing effect (the virus titre reduction not more than by 2.5 Ig). The employment of MSA and MCA gives most complete information on antigenic restructuring of influenza virus HA at the site level and more subtle structures, epitopes, in the process of evolutionary variability. PMID- 1858362 TI - [Effective purification of substrate DNA from poliomyelitis vaccinal preparations]. PMID- 1858363 TI - [Development of a test system for demonstrating the tick-borne encephalitis virus using lanthanide immunofluorescence analysis]. PMID- 1858364 TI - [Use of immunoenzyme analysis for detecting antibodies to respiratory syncytial virus with the aid of a conjugate of staphylococcal protein A with peroxidase]. PMID- 1858365 TI - [Properties of the attenuated strain 230 of Venezuelan equine encephalomyelitis virus]. PMID- 1858367 TI - The diabetes mellitus pandemic. PMID- 1858366 TI - [Does Rift Valley fever threaten "encroachment" into the southern regions of the USSR?]. PMID- 1858368 TI - Helicobacter pylori. AB - Since 1983, rapid advances in the knowledge of Helicobacter pylori have given new insights into the pathogenesis of upper gastrointestinal diseases. Several methods are now available for the diagnosis of the infection. Antimicrobial therapy has emerged as a new and effective treatment for peptic ulcer disease in a proportion, as yet to be determined, of patients in the Caribbean. PMID- 1858369 TI - An analysis of psychiatric inpatient admissions from a defined geographic catchment area over a one-year period. AB - The psychiatric inpatients from a defined geographic catchment area of 100,159 were analysed for the year 1986. The inpatient treated prevalence was 5 per 1,000 of the population over 15 years of age. There were 85 long-stay patients and 413 admissions during the year. Thirty-eight per cent of all admissions for 1986 had schizophrenic psychoses, 34% had alcohol and drug disorders, and 15% had affective disorders. Forty-nine per cent of first admissions had alcohol and drug disorders, and 28% had schizophrenic psychoses. Schizophrenic psychosis was the diagnosis in 61% of those patients who had more than 3 previous admissions. Substance abuse, acute schizophrenic psychosis and chronic schizophrenic psychosis accounted for 72% of admissions for 1986. The duration of stay in hospital was longer for female patients than for male patients for each of the main diagnostic categories. The need for epidemiological and hospital utilisation studies to provide essential data for the rational planning of psychiatric services in Trinidad and Tobago is emphasized. PMID- 1858370 TI - A retrospective study on hypothyroid patients. AB - A retrospective study of 58 hypothyroid patients attending the Endocrine Clinic, University Hospital of the West Indies, Jamaica, between July and August 1989, was undertaken. The age range at initial presentation varied from one month to eighty-four years. The majority of cases (51 or 87.9%) were between 21 and 70 years. There were 50 females (86.2%) and 8 males (13.8%). The underlying causes were idiopathic hypothyroidism (35 or 60.3%), posthyroidectomy (13 or 22.4%), post I131 therapy (6 or 10.4%), panhypopituitarism (3 or 5.2%), hypophysectomy (1 or 1.7%). Biochemical parameters used in diagnosis were serum thyroxine (T4) and thyroid-stimulating hormone (TSH). Forty-six patients (79.2%) had elevated TSH, indicative of a high correlation of elevated TSH with hypothyroidism. Duration of symptomatology prior to diagnosis was one year in 27 patients (46.5%), 2-10 years in 23 (39.6%) and 10 years in 4 cases (6.9%). The major presenting signs and symptoms were lethargy (20 or 34.5%), anaemia (mixed normochromic, microcytic (16 or 27.6%), slow relaxation of tendon reflexes (16 or 27.6%), coarsening of skin (15 or 25.9%), weight gain 10 or 17.2%), hoarseness (9 or 15.5%) and psychiatric symptoms (7 or 12%). The known association of primary hypothyroidism with other autoimmune disorders was not borne out in this study. The time-lapse in diagnosis from symptomatology emphasized the need for clinicians to be more alert to the subtle and varied presentation of hypothyroidism. PMID- 1858372 TI - Aspergillosis in a patient with acute lymphoblastic leukaemia. AB - A case is described of a 3-year-old boy with acute lymphoblastic leukaemia (ALL) who presented initially with aspergillosis of the nasopharynx. Fungal infection with Aspergillus species is not uncommon in immunosuppressed children, but this case is noteworth in that the disease presented at the onset of therapy rather than during the phase of treatment, with maximum immunosuppression following chemotherapy. This type of infection is usually associated with the treatment of acute non-lymphoblastic leukaemias (AML) rather than ALL, and prolonged periods of neutropenia which results from aggressive treatment. This patient responded rapidly to treatment with amphotericin B, coincident with resolution of his neutropenia as the underlying disease was treated, eventually eradicating the fungus. PMID- 1858371 TI - Peritonitis in acute peritoneal dialysis at the University Hospital of the West Indies (a five-year review). AB - The records of patients receiving acute peritoneal dialysis during the years 1983 1987 were retrospectively evaluated. Of a total of 59 patients receiving dialysis, 10 developed peritonitis. Staphylococcus aureus was the single most frequently isolated organism. However, gram-negative bacilli as a group were more common. We recommend the use of cloxacillin orally and gentamicin intra peritoneally as empiric antibiotic coverage until results of culture reports are available. PMID- 1858373 TI - A family with homozygous haemoglobin E in Trinidad and Tobago. PMID- 1858374 TI - Is MRCP (U.K.) a redundant qualification for graduates of D.M. (Internal Medicine), University of the West Indies? AB - M.R.C.P.(U.K.) and D.M. (Internal Medicine), University of the West Indies, are postgraduate qualifications that did, or now do, evaluate and set the quality of specialist Internal Physician training. Since the inception of the degree, graduates of D.M. (Internal Medicine), University of the West Indies, have developed sub-specialty interests and have been recognized as being of consultant status throughout the region and the world. D.M. is of a higher standard as it is an exit examination whereas the MRCP(U.K.) diploma is an entrance examination. Acquisition of the MRCP (U.K.) is expensive; travel to the U.K. is mandatory. Possession of MRCP (U.K.) is considered by most graduates of D.M. (Internal Medicine), University of the West Indies, to be unnecessary; it has not advanced their career in any discernible way. It should no longer be encouraged in any way at the University of the West Indies. PMID- 1858375 TI - [Experiences with Kahn's method of dentatotomy]. AB - Between 1980 and 1990, 37 patients with cervical spondylotic myelopathy and syringomyelia underwent posterior decompression by laminectomy and dentatotomy. The preoperative symptoms are compared with the postoperative status. Spasticity and pyramidal signs were reduced. In our opinion, Kahn's indication for dentatotomy as described in 1946 is obsolete today. However, we believe that after extensive decompressive laminectomy an additional mobilising effect is recommendable, so that Kahn's operation is still of relevance as an additional procedure in the treatment of this condition. PMID- 1858376 TI - [Indirect traumatic diaphragmatic rupture]. AB - Between 1969 and 1988 51 polytraumatized patients were treated for rupture of the diaphragm due to blunt trauma. In 39 cases the lesion was in the left hemidiaphragm, in 11 cases on the right side and in one case on both sides. Clinical investigation and posterior-anterior chest X-ray were the most important diagnostic procedures. A high percentage of ruptures was only detected intraoperatively during acute laparotomy/thoracotomy. Early or delayed surgery had no influence on the survival of patients. The prognosis depends on the severity of associated injuries, which are the main causes of death in these patients. PMID- 1858377 TI - [Repeat mass screening for fecal occult blood for the diagnosis of colorectal neoplasms in a rural district. Results of an informational campaign]. AB - In 1987/88 and 1988/89 we tested the population (aged greater than or equal to 40) of the district of Oberpullendorf in 2 series for faecal occult blood by means of the Hemdetect Test. In the first test series the test was offered to 18,233 persons and 8235 (45%) persons completed the test; 187 (2.3%) were positive. In the second series 6512 (36%) out of 18,241 completed the test and 472 (7.2%) persons were positive. The persons with positive results were examined by colonoscopy, gastroscopy, and abdominal sonography, in combination with routine investigations. Secondary compliance in these investigations was 92%. The screening method revealed 34 colorectal cancers with the favourable pathological staging: Dukes A 18 (53%), Dukes B 6 (18%), Dukes C 10 (29%), Dukes D 0. 11 polyps showing carcinoma in situ and 174 polyps (70% of which were adenomas) in 124 patients were treated by colonoscopy. In the meantime we have detected 14 "interval" cancers among people with a false negative test result, also at a favourable staging: Dukes A 6 (43%), Dukes B 4 (29%), Dukes C 4 (29%), Dukes D 0. In the non-responders we found 30 colorectal cancers at a much worse staging: Dukes A 7 (23%), Dukes B 10 (33%), Dukes C 8 (27%), and Dukes D 5 (17%). Screening for faecal occult blood in combination with the necessary investigations of the positive persons by colonoscopy is able to detect symptomless colorectal cancers at a less advanced pathological stage and enables the treatment of precancerous adenomatous polyps. An improvement in cumulative sensitivity is expected on annual repetition of screening for faecal occult blood. PMID- 1858378 TI - [Complicated course of a compression syndrome of the popliteal artery in a 36 year-old patient]. AB - The popliteal entrapment syndrome is an entity increasingly reported over the past few years. Anatomical variations should be considered if a localized stenosis or occlusion of the popliteal artery is diagnosed in a young, otherwise healthy individual. This case report documents a complicated course of the disease in a young man in whom diagnosis was made only after futile attempts of intraarterial lysis and dilatation at the time of a second operation. A complex crural reconstruction was necessary in order to revascularize the treatment limb. PMID- 1858379 TI - [The importance of hammer toe in the framework of complex changes of the forefoot]. PMID- 1858380 TI - Regarding: comment on the paper: Russell, G.A.: Physicians at the Ottoman Court. PMID- 1858381 TI - [New special agents registered in Austria. Zinnat (cefuroxime axetil, glaxo)]. PMID- 1858382 TI - A citation analysis of Austrian medical research and Wiener klinische Wochenschrift. AB - Criteria for the prediction of Nobel prize winners based on citation and predictor prizes are presented. The position of Austrian medical research and the role of the "Wiener klinische Wochenschrift" are compared to international standards. PMID- 1858383 TI - [Research on quality of life in clinical studies: what is it and how is it measured?]. AB - The failure to investigate quality of life looms as a major gap in clinical studies. It was the aim of the survey to demonstrate 1) the problem of defining quality of life, 2) the importance of measuring it, especially with respect to evaluating optimal therapy and 3) measurement instruments and scales (disease specific and overall well-being indices). Current remaining problems regarding quality of life research, as well as its use in clinical trials are discussed. It is stressed that quality of life should never be a mere slogan, but should be the focus for doctor and patient of interdisciplinary research regarding outcome of any therapy and indicator of its efficacy. PMID- 1858386 TI - [New special drugs registered in Austria. Losec (omeprazole)]. PMID- 1858385 TI - William Chamberlaine (1747-1822) and his Fothergillian Medal. AB - The Fothergillian Medal is awarded by the Medical Society of London for medical distinction. It was first presented in 1787 and, apart from a short interval 1803 1824, it has continued to be awarded until the present day. Of the original seven gold medals cast, only two are preserved. However, the Brettauer Collection in Vienna contains an unusual (third) Fothergillian Medal cast not in gold but in gilded silver, which is dedicated to William Chamberlaine. A search of the archives of the Medical Society of London has revealed the identity of William Chamberlaine who was Honorary Secretary of the Medical Society of London for eight years, and was awarded this special Fothergillian Medal in recognition of his services. PMID- 1858387 TI - Clinical syndromes with vasoconstrictor response. AB - Vasospasm implies reversible vasoconstriction that may diminish blood flow to the perfused tissues followed by an ischaemia of varying severity. The exact pathophysiology of the condition remains unknown to this day. Vasospasms are not only present in Raynaud's disease, migraine, Prinzmetal's variant angina, visual field defects and partially in low-tension glaucoma, but may also be involved in the pathogenesis of Crohn's disease. Vasospastic diseases may result from more than one mechanism. It is difficult to determine which of the underlying abnormalities is the most important in vasospastic syndromes of different vascular beds. PMID- 1858384 TI - [5-Fluorouracil (5-FU)/leucovorin in comparison to other current chemotherapy protocols in metastasizing colorectal carcinoma]. AB - 17 patients with metastasizing colorectal cancer were treated in a phase II-study with systemic intravenous chemotherapy (Petrelli N, Proc ASCO 286, 1987) consisting of leucovorin 500 mg/m2 in a 2 hr infusion and 5-fluorouracil (5-FU) 600 mg/m2 bolus one hour after the commencement of the leucovorin infusion. Limiting toxicities were gastrointestinal, in form of nausea/vomiting of WHO grade 3 (n = 1) and of diarrhoea of maximal grade 4 (n = 5), as well as haematological with a maximal nadir of leucocytes of WHO grade 4 (n = 1) and of thrombocytes of WHO grade 1 (n = 1). Of the 14 evaluable patients an objective response was achieved in 21% of cases (CR: n = 1, PR: n = 2). 64% of the patients showed no change and 14% showed progression of their disease, 7 out of the 17 patients have died; the median survival was 24 months. With respect to objective remission, our result of 21% response rate is lower than the median of 32% of 24 different studies comprising 695 patients; nevertheless, the present response rate is within the range observed in the published studies of between 0% and 67%. In order to estimate the antitumoral efficacy of the new regimen 5-FU/leucovorin more objectively, a retrospective comparison of the therapy regimens used most frequently in disseminated colorectal cancer (5-FU monotherapy, 5-FU/methotrexate (MTX), 5-FU/MTX/low dose leucovorin, 5-FU/cisplatin, 5-FU/leucovorin) has been performed. The continuous administration of 5-FU monotherapy, with an objective response rate of 26%, was superior to standard 5-FU monotherapy as a bolus injection or short-term infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858388 TI - [Serum thromboxane B2 and prostaglandin F2 alpha in familial combined hyperlipoproteinemia and familial hypercholesterolemia]. AB - In continuation of investigations on primary hyperlipidaemias, we determined serum thromboxane (TX) B2 and prostaglandin (PG) F2 alpha after standardized blood clotting in patients without hyperlipidaemia and without (group 1, n = 11) or with coronary heart disease (CHD; group 2, n = 5), in patients with familial combined hyperlipoproteinaemia and without (group 3, n = 4) or with CHD (group 4, n = 5), as well as in patients with familial hypercholesterolaemia and CHD (group 5, n = 5). TXB2 was detected by gas chromatography and PGF2 alpha by means of radioimmunoassay. The TXB2 level did not differ significantly between the groups, but there was a tendency to higher values in hyperlipidaemia, while in group 5 the level tended to decrease with rising serum LDL-cholesterol and in group 3 it tended to increase with rising serum apolipoprotein B. The PGF2 alpha level was significantly lower in group 4 than in groups 1 and 3. It showed in group 5 a negative correlation with serum LDL-cholesterol and in group 3 a positive correlation with serum triglycerides. PMID- 1858389 TI - [The artist as patient. A study of diseases of the locomotor system in orchestra musicians]. AB - Professional orchestral musicians, who are subjected to considerable long-term static and dynamic stresses in the course of their work, frequently suffer from disorders of the locomotor apparatus. The complaints are typically localized in the region of the shoulder and neck. There are indications that specific disorders are typically related to particular instruments. The data of this study suggest that there is an urgent need for physicians specializing in diseases commonly found in musicians and experienced in appropriate strategies of therapy. PMID- 1858390 TI - Community involvement in health development: challenging health services. Report of a WHO Study Group. PMID- 1858391 TI - [Crisis as a threat and a development potential--an introduction to classical crisis concepts]. PMID- 1858392 TI - [Goals and steps in crisis intervention]. PMID- 1858393 TI - [Suicidal crisis]. PMID- 1858394 TI - [Crisis and crisis intervention in dependency disorders exemplified by alcoholism]. PMID- 1858395 TI - [Crisis and crisis intervention in adolescence]. PMID- 1858396 TI - [Department of crisis intervention in a specialty office for child- and adolescent neuropsychiatry--report of initial experiences]. PMID- 1858397 TI - [Depressed patients in daily practice. 1: Relationship with depressed patients]. PMID- 1858398 TI - [Depressed patients in daily practice. 2: Drug treatment in depression]. PMID- 1858399 TI - [Causes or condition complex in the etiology of diseases]. PMID- 1858400 TI - [Abruptio placentae and responsibility of counseling--a balancing act]. PMID- 1858401 TI - [Multiple combination of individual combined modality cancer therapy within the concept of unified steps]. PMID- 1858403 TI - [The need for interpersonal relations and coping with stressful life events]. PMID- 1858402 TI - [Microbiologic diagnosis, antibacterial chemotherapy and prevention in dental care--a review]. PMID- 1858404 TI - [Myocarditis in childhood and adolescence]. PMID- 1858405 TI - [Rehabilitation of psychological diseases in the aged]. PMID- 1858406 TI - [Theoretical aspects of handedness]. PMID- 1858407 TI - [Acute poisoning caused by wood preservatives from the viewpoint of the Berlin (East) Central Toxicologic Information service]. PMID- 1858408 TI - Mediators of different lung cells and their function. PMID- 1858409 TI - Value of different bioptical methods in diagnostics. PMID- 1858410 TI - Bronchoalveolar lavage. PMID- 1858411 TI - Applied histochemistry and cytochemistry. PMID- 1858412 TI - Immunohistochemistry. PMID- 1858413 TI - Prevention of infections of the respiratory tract using the oral application of antigens. PMID- 1858414 TI - Lectin-specific receptors on BAL-cells. PMID- 1858415 TI - Pneumocystis carinii pneumonia in pulmonary pathology. PMID- 1858416 TI - Chlamydia pneumoniae--a new important respiratory pathogen. PMID- 1858417 TI - Laboratory diagnosis of Legionella infections. PMID- 1858418 TI - Mycobacterium malmoense infections. PMID- 1858419 TI - Demonstration of important enzymes for histochemical and cytochemical investigations. PMID- 1858420 TI - Demonstration of phospholipids (including surfactant lipids) by light microscopy. PMID- 1858421 TI - In situ hybridization. Principles and applications in pathology. PMID- 1858422 TI - Functional morphology of the tracheobronchial tree and the lung periphery. PMID- 1858423 TI - The human secretory immune system. PMID- 1858424 TI - Lymphocytes in the lung--localization and kinetics. PMID- 1858425 TI - [The significance of the Maillard reaction in human physiology]. AB - More than 50 years after Maillard's original paper describing the reaction of amino acids with glucose it was found that this reaction also occurs under physiological conditions in the human body. Initially, it was discovered that human hemoglobin contains protein-bound Amadori-products that are increased in diabetic patients with elevated blood glucose levels. Measurements of fructosylated hemoglobin are now widely used as an index of glycemia in diabetes. It was soon recognized that this postribosomal modification is common to other proteins in vivo like albumin, lens crystallins, proteins of the clotting cascade, collagens, lipoproteins, proteins of the cell membrane, and others. This may lead to alterations in structure and function of the respective protein. Later, the realization that long-lived proteins become browned, fluorescent, and insoluble with age, and at an accelerated rate in diabetes, suggested that later stages of the Maillard reaction might proceed in vivo and contribute to some of the pathophysiology associated with both aging and diabetes. Although the contribution of the Maillard products to the development of diabetic late complications is not fully understood, attempts are being made to prevent formation of late Maillard product with aminoguanidine, a drug currently under clinical testing. PMID- 1858426 TI - The Maillard reaction in vivo. AB - The Maillard or browning reaction between reducing sugars and protein contributes to the chemical deterioration and loss of nutritional value of proteins during food processing and storage. This article presents and discusses evidence that the Maillard reaction is also involved in the chemical aging of long-lived proteins in human tissues. While the concentration of the Amadori adduct of glucose to lens protein and skin collagen is relatively constant with age, products of sequential glycation and oxidation of protein, termed glycoxidation products, accumulate in these long-lived proteins with advancing age and at an accelerated rate in diabetes. Among these products are the chemically modified amino acids, N epsilon-(carboxymethyl)lysine (CML), N epsilon (carboxymethyl)hydroxylysine (CMhL), and the fluorescent crosslink, pentosidine. While these glycoxidation products are present at only trace levels in tissue proteins, there is strong evidence for the presence of other browning products which remain to be characterized. Mechanisms for detoxifying reactive intermediates in the Maillard reaction and catabolism of extensively browned proteins are also discussed, along with recent approaches for therapeutic modulation of advanced stages of the Maillard reaction. PMID- 1858427 TI - [The decomposition of reducing sugars and amines in the Maillard reaction]. AB - Through the Maillard reaction, occurring in food and in the human body, reducing sugars, amino acids and proteins are transformed. Some general and also specific degradation pathways for pentoses, mono- and disaccharides can be defined. The structures of the products are influenced by the type of amine (primary or secondary). During the degradation reactions C-C fissions of the sugars and amino acids (Strecker degradation) can be observed. Some Maillard products are suited as indicator substances to determine the extent of the Maillard reaction. PMID- 1858428 TI - [Effect of Maillard products and lysinoalanine on the bioavailability of iron, copper and zinc]. AB - Bioavailability of iron, copper, and zinc was investigated in suckling rats. The essential trace elements were given once either with several isolated Maillard products and with LAL, respectively, or with differently heat-treated formula diets. The isolated substances revealed effects on bioavailability of all the elements tested, either on the preabsorptive or on the postabsorptive level. The formula diets affected only the bioavailability of copper - even when fed for several weeks. PMID- 1858430 TI - [Evaluating the validity of short witness reports using behavioral and psychophysiologic parameters]. AB - Within the context of credibility assessment, the impact of behavioral and physiological adaptation and response patterns of truly and falsely testifying eyewitnesses was examined in a laboratory study. It was further examined statements concerning characteristics of the delict and the experimental situation itself. 20 subjects were instructed to truly or falsely testify after having witnessed a willful destruction. Eye movements, respiration, heart rate and skin conductance were recorded and analyzed by computer. Witnesses instructed to falsely testify showed elevated skin conductance responses and an increased variability of horizontal eye movements at the beginning of the session. Additionally, they also showed stronger responses in eye-blink rate, respiration rate and variability of skin conductance and heart rate to questions related to the behavior in the experimental situation. Reactivity to questions concerning the culprit was less pronounced. Results are discussed in terms of their application within the German law system. PMID- 1858429 TI - [Formation of IQ-compounds in meat and meat products]. AB - During meat processing mutagenic imidazoquinolines and imidazoquinoxalines ("IQ compounds") may be formed by Maillard reaction of reducing sugars, amino acids, and creatine/creatinine. IQ-compounds isolated from low-moisture model systems and meat extract by liquid-liquid-distribution were fractionated on a cation exchanger and separated on an RP phase. After acetylation the separated compounds were identified by gas chromatography/mass spectrometry based on their characteristic mass fragment ions. During heating the model systems at 100 degrees C the formation of IQ-compounds begins and greatly increases by further raising the temperature. In different amounts IQ-compounds could also be detected in commercially available meat extracts. PMID- 1858431 TI - [Invariance in relation to transformations: a comparison of space perception and imagined space]. AB - The present paper is based on the assumption of a functional equivalence between the processes of perception and imagination and a functional isomorphism between physical and phenomenal relations. The intention is to look for systematic deviations between 'measured', 'perceived' and 'imagined' space. Therefore a room was equipped with 32 pieces of furniture, giving it the appearance of a combined library and study room. A miniature model (1:10) of the room was constructed. In a two-factorial design with 10 experimental conditions, subjects performed model reconstructions. The first factor refers to cognitive modality and represents different amounts of information of the physical layout, the endpoints of the continuum being 'complete insight' and 'no insight'. The second factor is a rotation of the model during the reconstruction (0 degrees vs. 180 degrees). Data analysis is based on location and orientation measures of the objects and distinguishes between 'semantic' and 'geometric' errors. The main results are: Even under conditions of only partial insight the spatial relations of the missing objects can be consensually reconstructed. While the absolute amount of the reconstruction errors largely depends on the two factors (modality and rotation), substantial relations of the original room are preserved under the different experimental conditions. The results are in good accordance with the assumption of functional equivalence and are critically discussed with respect to the concept of functional isomorphism. PMID- 1858432 TI - [Decision making and professional experience: an experimental study of generating, evaluating and modifying diagnostic hypotheses]. AB - Experimental investigations on generation, evaluation, and modification of diagnostic hypotheses in symptom pattern classification revealed in different domains (e.g. clinical decision making) that reasoning in non-experts and experts differ in the 'content' (e.g. issue-directed substance of concepts) rather than in the 'form' of reasoning (e.g. number, specificity of hypotheses). These results are essentially accounted for by the experts' upper-level flexibility in the interpretation of data. In a two-factorial design (competence x predictive value of data), patients' clinical data with varying predictive value were given singularly in succession to two groups (experts and novices; n = 20) of subjects. The task of the subjects was (a) to name their assumptions and (b) give a summarizing decision on the--probable--diagnostic category of hypothetical cases. RESULTS: Between experts and novices no difference was found in the number and degree of specification of hypotheses; in summarizing decisions, experts considered more categories as plausible than novices; on patient data with low predictive value, experts considered more specific categories. The moment of hypothesis formation depends not on the competence level but on the predictive value of the patient's clinical data. PMID- 1858433 TI - [Changes in mood caused by staged, moderate physical activity]. AB - This experiment provides a test for the common sense knowledge that moderate physical exercise leads to mood improvement. Furthermore, it was tested whether light exercise intensifies negative feeling states or alleviates them. 30 female and 30 male students of psychology served as subjects (mean age 25.3 years, SD = 4.8). After being exposed to a mood induction procedure designed to elicit either a positive or negative feeling state, the subjects had to pedal a bicycle ergometer with 0, 50 or 75 Watt load. Cardiovascular variables and self-reports of mood states were assessed during a baseline period, after the mood induction, following the ergometer exercise, and after a follow-up period. The mood induction procedures were successful, but only for a short duration. Physiological activation was observed according to the ergometer loadings. Moderate physical exercise led to an increase of positive feeling states (Concentration) and a decrease of negative feeling states (Tiredness) in the follow-up period. Corresponding changes in tension related states could not be observed, probably due to the weakness of the mood induction procedure employed and the low level of energetic activation reached. PMID- 1858435 TI - [Experimental induction of emotional states--does addition of music improve self disclosure?]. AB - Two procedures to experimentally induce negative and neutral emotional states are compared: self-referent emotional statements (Velten, 1968) presented alone vs. combined with music. For female subjects selected according to their baseline mood, it could be shown that negative statements alone induced anger whereas in combination with music they evoked sadness, i.e. dependent on the procedure applied, the quality of the induced negative emotion changed. For the induction of a neutral state the combined procedure proved to be superior, especially to reduce a positive baseline mood. PMID- 1858434 TI - [Psychophysiologic chronometry: detection of facilitating and inhibiting processes in information processing using electroencephalographic and electromyographic data]. AB - The objective of the present research was to tally the potential usefulness of psychophysiological measures in the systematic analysis of human information processing. Different context conditions were established in two cued choice reaction time experiments. The context could either facilitate or inhibit the processing of an imperative stimulus. Event-related brain potentials (EEG-ERP) and event-related electromyograms (EMG-ERP) were recorded and from these biosignals latencies and duration times for different aspects of stimulus evaluation and movement execution were derived. The EEG-ERP provided measures for the time of primary stimulus categorization (N2), the time necessary to test actual stimulus information against stimulus expectancies (P3b), and the time necessary to check the decision about the stimulus-response mapping (pSW). From the EMG-ERP, processing times were derived which are related to the initiation of a motor program and to distinct sections of the movement trajectory. Results show that these latency measures react differently to different context manipulations. EEG-ERP measures, for example, reflected differences during stimulus evaluation which were not detectable in response- or EMG-derived movement times. The parallel analysis of EEG-ERPs and EMG-ERPs allowed delineation of processing modules which are responsible for particular context-dependent facilitation and inhibition effects. Moreover, the data revealed substantial overlap of evaluation times and movement times. This finding seems to be more compatible with a parallel processing model than with a strictly sequential model. PMID- 1858436 TI - Patients with burning mouths. PMID- 1858437 TI - Teaching the referral process--the perspective of a part-time faculty member. PMID- 1858438 TI - The transmandibular implant: review of the literature, indications, and report of 11 cases. PMID- 1858439 TI - [Assessment of the effect of ibuprofen and other non-steroidal anti-rheumatic drugs in experimental algesimetry]. AB - This paper describes an experimental method for the assessment of analgesic effects of NSAIDs in healthy human volunteers. Pain was induced by repeated controlled pinching of interdigital webs. The painfulness of the stimulus was assessed by the subjects at regular intervals on an electronically controlled visual analog scale. Furthermore, computer supported infrared thermography, laser Doppler flowmetry and photoplethysmography were used to measure the cutaneous vascular reactions. The results of two double-blind cross-over studies are described in which analgesic effects of acetylsalecylic acid, ibuprofen, and dipyrone were significantly demonstrated. In one of the studies it was also shown that ibuprofen reduced the local stimulus-induced vasodilatation. In summary, this algesimetric model seems to be suited to demonstrate the analgesic and perhaps also the antiinflammatory effects of NSAIDs in healthy subjects. PMID- 1858441 TI - [The course of pain with electronic diaries, real time measurements and time series analysis]. AB - Important physiological parameters such as blood pressure, ECG and others are measured today on a continuous basis or at fixed intervals and are documented together with the date and the time. Individual results and subjective data are ascertained through questioning the patient, observation or patient's self assessment and are documented with paper and pencil, without having any certainty of the exact time of ascertainment or that such is comprehensible. Battery operated microcomputers have been developed in the form of electronic diaries (E.D.) for patients. Upon emitting an auditory signal, the questions appear in the computer display, and the questions are then correspondingly answered by the patient. These answers are fed to the permanent data store and are transferred on line and processed at a later time in a PC. The time and data of the entries are simultaneously registered and are included in the complete document when it is later printed out. A capacity of 64 kbytes suffices to accommodate the data collected; likewise, the battery is sufficient for constant use. The entries are made as categorical data or numerically. Free-style entries are not possible. With the aid of a specially-developed program, the courses of a chronic pain syndrome in patients with degenerative joint diseases were studied. The percentage change in the pain course, benefit risk considerations, prognoses with the aid of sequential analyses and plausibility criteria can be calculated from the data. The advantages of this new instrument are its simple handling and reliable functioning. Its disadvantage is that it lacks the possibility to allow free-style entries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858440 TI - [The course and topography of pain in generalized tendomyopathies]. AB - The generalized tendomyopathy (fibromyalgia) is characterized by the characteristic picture of multilocular pain symptoms, severe pressure-type pain in the tendon insertions and muscles, vitality deficiency, sleep disturbance and other vegetative disorders as well as functional complaints and is often also characterized by an altered psychological condition. Nevertheless, the disease is often not recognized, resulting in extensive superfluous diagnostic procedures and sometimes invasive and useless therapeutic measures. The disorder develops on average in the 37th year of life and initially affects, mostly monolocular, the cervical and lumbar region. The further course of the disease is progressive or recurrent and extends over years, often over decades. The patients' quality of life is markedly impaired and in many cases they are no longer able to carry out their occupational and household work. The socioeconomic significance of the generalized tendomyopathy probably exceeds that of chronic polyarthritis. One problem is the still poor therapeutic possibilities and also the assessment of the treatment. It is, therefore, of great importance to follow the course of the disease and the pain course via hand measurement methods, so as to enable the evaluation of new, but also known therapies. Measuring instruments, which record the intensity and the topography of the pain, such as dolorimetry and the pain score, will be presented and discussed. One of the newest possibilities is the computerized recording of the current symptoms, which is made by the patient himself by means of an electronic pain diary. PMID- 1858442 TI - [Real time collection of pain profile in treatment with ibuprofen]. AB - In an open three-center pilot study, 17 patients suffering from chronic persistent pain syndrome, due to osteoarthritis of the hip and knee or spondylarthrosis, were treated orally with 1800-2400 mg Ibuprofen per day for 3 weeks. The chronic pain syndrome and joint status were assessed by the physician at the beginning, and after 7, 14 and 21 days. Self-assessments were made by the patients six times daily during the full study period by means of battery-driven electronic diaries (E.D.). The data entered by the patients were stored in the E.D. and after online transfer, processed and evaluated in a PC using appropriate software programs. E.D. were returned by 16 of 17 patients for evaluation. The technical functioning of the instrument was perfect; its use was accepted by patients and physicians. The closely-meshed real-time recording of pain course and other subjective data, such as adverse events or medication, etc., enables the physician to calculate more exactly and reliably improvement rates, as well as to carry out prognostic trend analyses and individual benefit-risk-ratio estimates. By comparing different kinds of data, each entered at the same time, plausibility checks are possible. The procedure presented here is considered to be a new valuable tool for reviewing subjective data from clinical drug trials. PMID- 1858443 TI - [Analysis of the circadian rhythm of pain]. AB - An electronic pulp tester was used to study the stimulus threshold in human teeth of 28 healthy volunteers for 1,5-4 days and the duration of local anaesthesia in 55 patients with caries. Rhythm analysis was performed with a non-linear fitting program on an IBM computer (PHARMFIT); in 21 out of the 28 volunteers significant daily rhythms in stimulus threshold could be detected. In the patients the maximum duration of local anaesthesia was after drug application at 2 p.m. PMID- 1858444 TI - [Validation of electronic by conventional pain diaries]. AB - A new type of electronic pain diary was validated in an open, randomized, crossover study. The main target variables were the comparison of the correctly realized pain assessment entries as well as the recording of the number of adverse events. Selected for the study were 20 patients, who were either hospitalized, partially-hospitalized or treated on an out-patient basis, with painful spondylogenic spinal syndrome or osteoarthritis of the trunk-proximal large joints. The patients were randomly-assigned to the two groups. The first group initially received the conventional diary and thereafter the electronic diary; the sequence was reversed for the second group. The drug therapy consisted of the NSAID, Ibuprofen, at an individually-adjusted dosage. Additional therapeutic measures were carried out by all the patients. The electronic pain diary proved to be equivalent to the conventional diary with regard to adherence of the pain assessment entry times. At a defined equivalence range of +/- 20%, the statistical comparison showed that the limits were never exceeded. The equivalence test of Anderson-Hauck showed a significance level of p less than 0.0001. The minimum equivalence range was +/- 2%. It therefore follows, that the conventional method of data recording can indeed be fully replaced by the electronic method. Comparing the individual data of the 16 patients, from whom entries with both the electronic as well as the conventional pain diaries were submitted, a clear tendency for increased entries on adverse events in the electronic diary (C.D. 6.4 +/- 10.5/E.D. 36.4 +/- 44.1) was demonstrated. No significant difference, however, was shown for the number of patients making data entries on adverse events in the electronic pain diary compared to those patients, who made their entries on adverse events in the conventional diary. According to the data from the physicians and patients, the Ibuprofen treatment results in an improvement in 90%/75% of cases, respectively. Likewise, the functional impairment of the affected joints as well as the swelling decreased markedly. The advantages of the electronic data recording system, i.e. closely meshed controls can be carried out, transcriptional errors are minimized, data can be processed on-line, no possibility to subsequently change an entry, stand in contrast to the feature that there is no possibility to make free-style entries. The employment of the electronic system in the recording of individual data and subjective data represents a substantial improvement with regard to the quantity and quality of the data. PMID- 1858445 TI - [Pathogenetic aspects of arthrosis and its therapeutic aspects]. AB - The hitherto accepted idea that articular cartilage is merely bradythrophic tissue which, like a shoe sole, is subjected to continuous wear and tear, as a whole must be revised by considering the growing biochemical, biophysical, and ultrastructural research of the matrix components. The chondrocyte is the single living element of the cartilage: Type-II collagenous fibres and the proteoglycans are its products. To what extent the regulation of collagen production and above all the steady-state regulation is controlled by a superordinating regulation is still not known. However, we must absolutely postulate such. In the mechanics of the joint there are two antagonists which confront each other: 1. the (to a large degree) intellectually regulatable physical strain; and 2. the quality of the cartilage matrix. This represents a refined hydroelastic system. Research into the biochemistry and biophysics continuously provides an increasing abundance of new data on the molecular biological mechanisms, which 1. induce the degradation of proteoglycans and collagens; 2. increase the synthesis of the matrix components; 3. antagonize the degradation, and 4. inhibit the synthesis. In addition, an interaction of these factors can also be expected. Moreover, new information on the components and structures of the matrix is continuously gathered. Up to now, we know of 14 different types of collagen, which on the other hand are accessible to various degradative enzymes. The most important, and -from the standpoint of the biomechanics--the most interesting element/building block is, however, the proteoglycan molecule, whose excessive water-binding capacity enables the hydroelasticity of the hyaline cartilage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858446 TI - [Experiences with 800 mg ibuprofen retard in ambulatory patients with activated osteoarthrosis and extra-articular rheumatic manifestations]. AB - The efficacy and tolerance of ibuprofen retard at a dose of 2 x 800 mg daily was investigated in an open multicenter study over a period of 3 weeks on 7931 out patients with activated degenerative joint disease and/or extraarticular rheumatic symptoms. The overall assessment of the treatment, made by the patients and physicians at the end of the observational study, was positive in 94.7% and 95.7% of the cases, respectively. The therapy was assessed as inadequate in only 5.2% and 4.3% of the cases, respectively. The patient's compliance was assessed by the physicians as being high at 92.6%. Adverse events during the treatment were observed in 7.8% of the patients; these concerned mainly intestinal complaints. Gastrointestinal bleeding was observed in five cases. One patient died from a heart attack during the observational study; this was not related to the drug therapy. The frequency of side effects was within the range of the findings from earlier studies with conventional drug formulations. It can be concluded from the results obtained that ibuprofen 800 retard is well-suited for and demonstrates a good tolerance in the treatment of acute, chronic-persisting, and chronic-intermittent painful conditions of degenerative joint disease and extraarticular rheumatic symptoms. PMID- 1858447 TI - [Pancreatic pseudocysts and their interdisciplinary therapy]. AB - A retrospective analysis was performed of 87 patients with pancreatic pseudocysts admitted at the Dept. of Surgery University of Hamburg from 1985 to 1989. Pseudocysts as a result of chronic pancreatitis were found in 54%. 42 patients underwent 49 operations, 35 have been drained endoscopically. In 10 cases there was spontaneous remission. 25 patients were treated by Roux-en-Y cystojejunostomy. In 14 patients a resection of the pancreas was performed. The mean follow-up interval was 26 (operative treated) and 22 months (endoscopic treatment). 50% of all patients in both groups reported pain relief. The mortality in operated patients was 7% and 0% for endoscopic treatment. In ten cases a recurrent disease was observed. PMID- 1858448 TI - [Results of Billroth I and Billroth II stomach resection]. AB - Between 1966 and 1986, Billroth I and Billroth II resections for gastroduodenal ulcers were performed at the Department of Surgery, Friedrich Schiller University, Jena. Early postoperative complications after Billroth II (14.6%) were somewhat rarer than after Billroth I (19.4%), however, bore a greater risk. With a permanent cure accounting for 85%, the comparison of both procedures reveals no significant differences in the late results. In gastric ulcer, Billroth's first method should be given preference because it can be carried out more rapidly in technical respect and takes digestive physiology into account. PMID- 1858449 TI - [Disorders of wound healing of the sacral cavity after abdomino-perineal resection of the rectum]. AB - In 95 patients it was necessary to perform abdominoperineal resection and colostomy due to malignant tumours of the rectum, the anus, as well as gynaecological tumours. After standardized preoperative preparation and comparable operative techniques in more than 93 per cent of the cases we performed suction drainage of the sacral cavity. In 86 per cent we observed primary perineal wound closure and the patients were spared lengthy secondary wound healing. PMID- 1858450 TI - [Operated mechanical ileus of the small intestine]. AB - Causes, pathophysiology, diagnosis, therapy and a retrospective analysis of small bowel obstruction were reviewed. 85 patients were operated during a 5-year period. The etiology of obstruction were adhesions (45 cases), hernia (20 cases) and 20 other cases. The mortality rate for the series was 8%. The most important factor of prognosis is the early operative treatment. PMID- 1858451 TI - [Preoperative hemodilution as a possibility in autologous blood transfusion. A report of experiences]. AB - The various methods of autologous blood donation are gaining importance in clinical practice. Acute preoperative isovolaemic haemodilution represents a cost cutting and readily practicable option. It is a method that brings positive haemodynamic effects and improves the blood's flowing properties by lowering its viscosity and raising cardiac output, as well as avoiding the dangers associated with foreign blood transfusion. Risks to the patient can largely be eliminated by keeping an eye out for contra-indications and ensuring careful perioperative monitoring. The successful use of this method depends on a clear organizational concept and close collaboration between surgeons, anaesthesists and transfusions specialists. PMID- 1858452 TI - [Indications for resection of Meckel's diverticulum]. PMID- 1858453 TI - [The value of serum endotoxin determination after gastrointestinal interventions]. AB - Serumendotoxins were measured in 11 patients after gut surgery and compared with healthy people as a standard. In cases of uncomplicated course 3 to 4-fold raised serumendotoxin levels were observed in a typical two-peak pattern. It was not before the fifth day following operation that serum levels declined constantly. In contrast to these findings, patients suffering from septic complications showed a permanently raised endotoxin level, which correlated well with their clinical course. Therefore single peaks of serumendotoxin measured after operation should not be overvalued. Constantly raised levels following operation, however, may indicate some kind of septic complication. PMID- 1858454 TI - [Our surgical heritage. Albert Fromme. His 110th birthday]. PMID- 1858455 TI - Serological (Em2-ELISA) and parasitological examinations of fox populations for Echinococcus multilocularis infections. AB - Serum or body fluid samples of 1,006 foxes were investigated in an ELISA for antibodies against a highly sensitive and specific antigen (Em2-antigen) of Echinococcus multilocularis. Parasitological examinations of the intestines and simultaneous serological examinations were carried out in 505 foxes: A group of 98 blue foxes (Alopex lagopus) from Norwegian fox farms did not contain intestinal stages of E. multilocularis and was clearly sero-negative in Em2 ELISA. On the other hand in red foxes (Vulpes vulpes) originating from European areas known to be endemic for E. multilocularis the following average prevalence rates were found: 244 foxes from Southern Germany, E. multilocularis prevalence 55% and sero-prevalence 60%; 139 foxes from Austria, E. multilocularis prevalence 4% and sero-prevalence 12%. Serological identification of individual foxes with or without intestinal E. multilocularis infection was not possible. Only serological (no parasitological) examination in 402 foxes originating from endemic areas in Switzerland resulted in a sero-prevalence rate of 37%. Sero prevalence was only 6% and 4% in 54 and 26 other foxes, respectively, originating from Swiss and German areas where E. multilocularis has not yet been reported. Negative control Norwegian (farmed) silver foxes (n = 43) were all sero-negative. The specificity of the Em2-ELISA was confirmed by negative Em2-serologies with sera from dogs infected with intestinal and tissue dwelling helminth species (with the exception of two from 24 dogs infected with E. granulosus).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858456 TI - Experimental oral Salmonella dublin infection in calves. A bacteriological and pathological study. AB - Groups of calves (6-7, 12-14 and 24-28 weeks old) were orally infected with different numbers of the virulent Salmonella dublin strain SVA47. For the 6-7 weeks old calves the LD50-dose was estimated to be 1 x 10(7) bacteria. A dose of 10(9) bacteria was lethal within 24 hrs with the calves dying from septicemia and an acute necrotizing panenteritis. Calves 12-14 weeks old given 2 x 10(10) SVA47 bacteria succumbed to a progressive enteritis within one week. The 24-28 weeks old calves were resistant to an infective dose of 1 x 10(10) SVA47 bacteria. In the 6-7 and 12-14 weeks old calves SVA47 could be recovered from the entire intestinal tract, the liver and the spleen. In the oldest calves S. dublin SVA47 was recovered only from fecal specimens. However, the immunohistopathological examinations, using an S. dublin O-antigen-specific mouse monoclonal antibody and PAP-staining, showed the presence of S. dublin SVA47 in all tissues of the intestinal canal from calves of all ages and with a special affinity for the columnar enterocytes of the terminal jejunum and ileum, the follicle-associated epithelium over the Peyer's patches, and glandular tissues in the duodenum, tonsillar area and the lungs. Surviving calves responded with serum antibody titers against the O-antigenic lipopolysaccharide which appeared in the order IgM followed by IgA, IgG1 and IgG2. PMID- 1858457 TI - A field study of Mycoplasma bovis infection in cattle. AB - After an outbreak of mastitis in cattle caused by Mycoplasma bovis a study was made in 5 herds with recent cases (principal herds) and in 4 control herds. In the principal herds, M. bovis was isolated from milk samples, nasal swabs, and from one vaginal swab. M. bovis was also isolated from nasal swabs of calves in 2 of the 4 control herds, whereas all milk samples and vaginal swabs from the control herds were negative. Evaluation of serum antibody titres to M. bovis among non-mastitic animals of 3 principal herds and 1 control herd showed no difference in distribution of the titre values, which generally were low. However, cows excreting M. bovis in the milk had high antibody titres. The way of introduction to the herds and the spread of the infection within the herds could not be established by the study, which was supplemented by a DNA restriction fragment analysis of a number of M. bovis isolates. PMID- 1858458 TI - Economic and production consequences of liver fluke disease in double-muscled fattening cattle. AB - The frequency of liver fluke disease in fattening units was determined by the analysis of random faeces samples issued from 1,513 Belgian White Blue bulls aged from 5 to 7 months and weighing from 200 to 300 kg. 12.5% of the investigated bulls were positive for liver fluke disease. These bulls were spread over 56.5% of the investigated fattening units. Furthermore the infestation rate varied from 0 to 33.3% inside the fattening units. In order to assess the economic consequences of bovine fascioliasis in double-muscled cattle and the beneficial effects of a treatment against such a disease, a trial including 30 Belgian White Blue bulls, weighing 365 +/- 9 kg and aged from 10 to 12 months, was conducted in a selected fattening unit. On the basis of faecal examinations, the 30 animals were subdivided in negative (group A; n = 10) and positive animals (n = 20) for fascioliasis, the latter being either treated with nitroxinil (group B; n = 10) or not (group C; n = 10) on day 0 of this trial which was conducted during 75 days. The daily body gains in group C (1.661 +/- 0.140 kg) were significantly lower than those in group A (1.975 +/- 0.120 kg). On the other hand there was no significant difference between the daily body gains registered in group B (1.960 +/- 0.085 kg) and A. The estimated financial loss, due to flukes and accounted on a 75 day-period, averaged 2,748 Belgian Francs per bull in group C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858459 TI - [Detection of antibodies against the larva of Anisakis simplex in the pollock Pollachius virens using ELISA]. AB - From the fact that older saithes (more than 5 years old) are showing significantly lower prevalence of attack by Anisakis larvae in lateral muscle than younger saithes (3-4 years old), the question arises if this phenomenon is based on a specific immune response. Therefore we have investigated serum samples from saithes of different ages by using an indirect ELISA to estimate the antibody-titer against excretory-secretory Anisakis antigen. Results showing a moderate correlation (r = 0.66) between the height of titer and the age of underfeeding saithes (post spawning) and a close correlation (r = 0.93) of saithes in an optimal condition (pre spawning). It may be concluded that the migration-distance and the lifetime of Anisakis larvae in lateral-muscle is influenced by a specific immune response which increases with the age of the saithes. PMID- 1858460 TI - Pathogenesis of experimental combined infections with Isospora suis and rotavirus in conventional and gnotobiotic piglets. AB - 51 gnotobiotic and 63 conventional, one-, or two-days-old piglets were divided into five groups and infected orally either with Isospora suis or rotavirus alone, or with both agents simultaneously or successively with alternative sequences and various intervals. 15 gnotobiotic and 10 conventional piglets served as controls. The development of small intestinal lesions after infection with I. suis was biphasic. The dominant alteration resulting from rotavirus infection was villus atrophy, considerably more pronounced and extensive in gnotobiotic than in conventional piglets. Synergistic action of I. suis and rotavirus was manifested both clinically, and morphologically. This action culminated at the time of the actual, or presumed development of merogony of I. suis, i.e. on DPI 3 to 5. The action develops only if the intestinal epithelium is damaged functionally and morphologically by a preceding rotavirus infection. It is concluded that the synergistic action is based on a competition of rotavirus and I. suis for mature, enzymatically active absorptive cells. PMID- 1858461 TI - A note on diseases of mink. AB - The paper describes in brief the findings in 5,616 autopsies of adult mink, performed at the Institute of Pathology-CIC, La Plata, during the last five years. Nearly all these carcasses, coming from the most important ranches, were examined bacteriologically and histopathologically. Observations about the incidence of different causes of death, its distribution annually and prophylactic measures were reported. It concludes that Aleutian disease is the most important cause of death and produces severe economic losses. PMID- 1858463 TI - Economic and production repercussions of deworming by pulse release device and oral suspension in grazing double-muscled fattening cattle. AB - In this field trial, the repercussions of 2 administration forms of oxfendazole, namely a single administration of a front-loaded device (group 1; n = 18) and a repeated administration of a 90.6 per cent oral suspension (group 2; n = 18), were compared in first season-grazing double-muscled fattening bulls. The comparison was based on the production performances, the mean worm egg counts and the product- and labour-costs. The daily body gains determined on the whole trial period, i.e. 1.312 +/- 0.055 kg and 1.270 +/- 0.056 kg for groups 1 and 2 respectively, and mean worm egg counts per gram (on days 0 and 130:200.0 +/- 44.3 and 94.4 +/- 27.4 for group 1; 366.7 +/- 98.4 and 100.0 +/- 33.6 for group 2) did not differ significantly between the two groups. However, the total costs were lower with a front-loaded device (1,021 Belgian Francs) than with oral suspension (1,248 Belgian Francs per bull). PMID- 1858462 TI - Mycobacterial antigen detection by immunohistochemistry in goat paratuberculosis. AB - An immunohistochemical method (PAP) for a microscopic diagnosis of paratuberculosis in goats is described as an alternative method to the Ziehl Neelsen technique. Mycobacterial antigens are only found in enteric and mesenteric lymph node lesions. This method is the most sensible, particularly in cases in which there are no paratuberculosis lesions and the Ziehl-Neelsen technique shows no acid-fast bacilli (AFB). PMID- 1858464 TI - [The role of lipopolysaccharides in preserving the viability of bacteria in air]. PMID- 1858465 TI - [The typing of Legionella pneumophila strains by using monoclonal antibodies to the cytolysin]. AB - Studies on the typing of L. pneumophila strains of serogroup 1, isolated from patients and environmental objects, have been made with the use of monoclonal antibodies (McAb) to cytolysin. The results of the comparison of the specificity of our McAb with that of a commercial set McAb obtained from the USA make it possible to recommend preparations based on McAb to cytolysin for the detection of L. pneumophila pathogenic strains of serovar 1. The use of FITC- and peroxidase-labeled McAb to cytolysin permits the reduction of the time necessary for the diagnosis of Legionella infections and the detection of the antigen in a dose of 10 ng/ml. PMID- 1858467 TI - [The current characteristics of the salmonellosis epidemic process in the USSR]. PMID- 1858466 TI - [The pharyngeal beta-hemolytic streptococcal carrier state among blood donors]. AB - 459 blood donors aged 18-50 years were examined in 1987-1988 in Moscow. Among them, carrier state with respect to beta-hemolytic streptococci was detected in 107 donors (23.3%). The number of carriers gradually decreased with the increase of age of the examined donors. Group C streptococci occurred least of all (6.9%). Group A beta-hemolytic streptococci were isolated in 16.7% of the carriers. The isolation rate of streptococci from blood achieved its maximum in autumn and winter months and did not depend on preceding diseases, unhealthy working conditions, the rhesus factor and, with the exception of group A streptococci, the blood group. Among tonsillectomized donors carrier state with respect to beta hemolytic streptococci occurred 2.2 times less frequently than among donors who had not undergone tonsillectomy. Carrier state with respect to beta-hemolytic streptococci was accompanied by higher levels of salivary sIgA antibodies to polysaccharide A, serum antibodies to polysaccharide A and circulating polysaccharide A. All beta-hemolytic streptococci were sensitive to erythromycin. All groups of streptococci showed the highest percentage of cultures resistant to gentamicin and tetracycline. In 100% of cases group A streptococci were sensitive to benzylpenicillin, methicillin, ampicillin, erythromycin and lincomycin. PMID- 1858468 TI - [A new prospective vaccine against tick-borne encephalitis]. PMID- 1858469 TI - [The heterogeneity of collection strains of Yersinia pseudotuberculosis and their molecular biological properties]. AB - The capacity of Y. pseudotuberculosis strains for disassociation with the appearance of S- and P-forms has been studied. Strains 852 and 9547 show high stability in S-forms, their conversion into R-forms occurring at 40-42 degrees C. Strain 6953 shows pronounced polymorphism and instability of its associations at different growth temperatures. Strain 9532 exists in S- and R-forms which retain their stability during numerous subculturings at different growth temperatures and prolonged storage. This strain has plasmids of 130, 72.2, 5.7 kb. All plasmids are retained in S- and R-forms, i. e. the dissociation of the strain is not accompanied by the loss of plasmids. The conversion of the strain from the S form into the R-form leads to changes in the structure of lipopolysaccharide and the composition of low-molecular (less than 23 kD) proteins in the outer and inner membranes. In tests on guinea pigs the LD50 of the R-form of the strain is tenfold greater than that of its S-form. The dissociants of strain 9532 are transformed by plasmid DNA with equal efficiency and equally inherit them without selective pressure. PMID- 1858470 TI - [The dynamics of the morphological changes in the tissues after the subcutaneous administration of vaccines against Q fever]. AB - The comparative study of the dynamics of morphological changes in tissues of guinea pigs after the subcutaneous injection of chemical, live and combined vaccines against Q fever during the period from 12 hours to 90 days was made. All vaccines under study were shown to produce a pronounced local damaging effect. Two periods were tentatively discriminated in the dynamics of changes: the early phase (till 48 hours) and the late phase (days 2-90). At the early stage the most pronounced changes were registered after the injection of the combined vaccine. At the late phase the use of the chemical and combined vaccines was accompanied by the appearance of secondary hemorrhages into newly formed connective tissue. Starting from day 30, practically no deviation from the normal state of tissues were registered at the site of injection. PMID- 1858471 TI - [The nonspecific changes in the immune system to the administration of the membrane-ribosomal fraction of the causative agent of pseudotuberculosis]. AB - Nonspecific changes in different elements of the immune system of animals under the action of Y. pseudotuberculosis membrane-ribosomal fraction (MRF) with high protective potency have been studied for the purpose of the analysis of the preparation for immunological safety. MRF has been shown to produce no changes in humoral immune response to antigens of different nature or to enhance this response, to produce no essential effect on the intensity of the reaction of delayed hypersensitivity to sheep red blood cells and to stimulate phagocytic processes in peritoneal macrophages and polymorphonuclear leukocytes. PMID- 1858472 TI - [A comparative study of the immunological properties of peptidoglycans of different origins]. AB - The action of peptidoglycans (PG) of different origin has been experimentally studied in vivo. In these experiments PG of bacterial origin, such as blastolysin (BL), and synthetic PG, viz. muramyldipeptide (MDP) and its analog glucosaminylmuramyldipeptide (GMDP) have been used. Their toxicity, allergenic action, their effect on the phagocytic activity of peritoneal exudate macrophages (PEM), the accumulation of antibody-producing cells in the spleen, antibody titer in the blood serum and delayed hypersensitivity to nonbacterial antigens have been determined. As revealed in this study, BL does not differ from MDP in its toxicity and allergenic action. The phagocytic activity of PEM under the influence of BL only insignificantly differs from their activity under the influence of MDP, but is lower than under the influence of GMDP. The adjuvant action of BL is somewhat higher than that of synthetic PG. PMID- 1858473 TI - [The therapeutic use of diucifon-activated immunocytes in adoptive transfer in mice with burn trauma complicated by Pseudomonas aeruginosa infection]. AB - The effectiveness of the therapeutic use of diucyphone-stimulated syngeneic spleen cells was studied in mice with a burn trauma complicated by P. aeruginosa infection. For this purpose CBA mice were subjected to a burn of degree IIIa, covering 30% of their body surface, the wound was infected with P. aeruginosa strain, and 24 hours later spleen cells were taken from some of these animals. The spleen cells, incubated for 3 hours with or without diucyphone at a concentration of 10-100 micrograms/ml, were washed and reinfused intravenously to the remaining animals. The injection of diucyphone-treated spleen cells was shown to greatly increase the survival rate of the animals, to accelerate healing processes and to enhance the proliferative response of spleen cells to mitogens (phytohemagglutinin, concanavalin A) and interleukin-2. A conclusion was made on the efficacy of the therapeutic use of diucyphone-activated immunocompetent cells in cases of immunodeficiency induced by burn infection. PMID- 1858474 TI - [The use of melamine-formaldehyde latex in the automated analysis of immunocompetent cells]. AB - The optimization of the loading of monodispersed melamine-formaldehyde latex with fluorochrome has permitted its use as indicator material, equally suitable both for the visual evaluation of the reaction of phagocytosis and for the automated evaluation of this reaction by means of a scanning fluorescent microscope. The study has shown the possibility of using fluorescent melamine formaldehyde latex for the evaluation of the phagocytosis of mouse peritoneal macrophages and human blood cells, as well as the analysis of the surface receptors of immunocompetent cells. PMID- 1858475 TI - [The role of macrophages in mediating the immunostimulating effects of low frequency ultrasound]. AB - The action of low-frequency ultrasound on the body has been shown to lead to the stimulation of specific immune response, as well as immunological memory cells. The effects of low-frequency ultrasound are seemingly realized through the macrophage system of immunity, i. e. the action of ultrasound leads to the stimulation of the functional activity of macrophages, their metabolism, while blocking the macrophage system of immunity with carraginal abolishing the effects of ultrasound. PMID- 1858476 TI - [Approaches to the molecular epidemiology of the rickettsioses]. PMID- 1858477 TI - Stability properties of proliferatively coupled cell replication models. AB - To address the possibility that proliferative disorders may originate from interactions between multiple populations of proliferating and maturing cells, we formulate a model for this process as a set of coupled nonlinear first order partial differential equations. Using recent results for the asymptotic behaviour of the solutions to this model, we demonstrate that there exists a region of coupling coefficients, maturation rates, and proliferation rates that will guarantee the stable coexistence of coupled cellular populations. The analysis shows that increases in the coupling between populations may ultimately lead to a loss of stability. Furthermore, the analysis indicates that increases (decreases) in the maturation and/or proliferation rates above (below) critical levels will lead either to instability in the populations or the destruction of one population and the persistence of the other. PMID- 1858478 TI - On the role of gravity and positional information in embryological axis formation and tissue compartmentalization. AB - The idea that gravity affects dorso-ventral polarization in anouran development contrasts with the theories of self-organization through reaction-diffusion processes. As a result of a literature study we discuss the role of gravity in embryological axis formation and speculate on an influence of gravity on tissue compartmentalization. The involvement of compartmentalization in tissue homeostasis is discussed in the light of the recent progress in mammalian cell culture studies. PMID- 1858480 TI - On the fundamental nature of perception. AB - The process of recognition or isolation of one or several entities from among many possible entities is termed intellego perception. It is shown that not only are many of our everyday percepts of this type, but perception of microscopic events using the methods of quantum mechanics are also intellego in nature. Information theory seems to be a natural language in which to express perceptual activity of this type. It is argued that the biological organism quantifies its sensations using an information theoretical measure. This, in turn, sets the stage for a mathematical theory of sensory perception. PMID- 1858479 TI - Computer modelling of neural tube defects. AB - Neurulation, the curling of the neuroepithelium to form the neural tube, is an essential component of the development of animal embryos. Defects of neural tube formation, which occur with an overall frequency of one in 500 human births, are the cause of severe and distressing congenital abnormalities. However, despite the fact that there is increasing information from animal experiments about the mechanisms which effect neural tube formation, much less is known about the fundamental causes of neural tube defects (NTD). The use of computer models provides one way of gaining clues about the ways in which neurulation may be compromised. Here we employ one computer model to examine the robustness of different cellular mechanisms which are thought to contribute to neurulation. The model, modified from that of Odell et al (Odell, G.M., Oster, G., Alberch, P. and Burnside, B., (1981)) mimics neurulation by laterally propagating a wave of apical contraction along an active zone within a ring of cells. We link the results to experimental evidence gained from studies of embryos in which neurulation has been perturbed. The results indicate that alteration of one of the properties of non-neural tissue can delay or inhibit neurulation, supporting the idea, gained from observation of embryos bearing genes which predispose to NTD, that the tissue underlying the neuroepithelium may contribute to the elevation of the neural folds. The results also show that reduction of the contractile properties of a small proportion of the neuroepithelial cell population may have a profound effect on overall tissue profiling. The results suggest that the elevation of the neural folds, and hence successful neurulation, may be vulnerable to relatively minor deficiencies in cell properties. PMID- 1858481 TI - Intermittent diazepam prophylaxis in febrile convulsions. Pros and cons. AB - Major cohort studies document that the long-term prognosis for most children with febrile convulsions (FC) is excellent. The 2 main treatment alternatives so far have been long-term prophylaxis with phenobarbital or valproate or no prophylaxis at all. Phenobarbital at times of fever is ineffective and obsolete. Consensus has emerged that long-term prophylaxis with antiepileptic drugs is rarely justified in FC considering the side effects and the favourable prognosis. No treatment at all does not appear quite satisfactory either, as FC have a high recurrence rate, disrupt family life and may have emotional consequences for the family. Moreover, all FC children face a risk, although admittedly low, of subsequent long-lasting potentially central nervous system (CNS)-damaging seizures. However, 2 further options exist: treatment with rapid-acting benzodiazepines solely at times of greatest risk, i.e., at high fever or at renewed seizures. Several clinical trials have confirmed that intermittent diazepam prophylaxis by way of a few doses of the drug per year provides effective seizure control and reduces the recurrence rate by one half or two thirds. The treatment is feasible and cheap, well tolerated by the child and well accepted by the parents. Compliance problems are common and only partly abatable. Trivial side effects are frequent. Transient respiratory apnoea does occur, but 15 years' experience substantiates that serious side effects are remarkably rare. Acute anticonvulsant treatment with rectal diazepam in solution given by the parents to stop ongoing seizures and to prevent immediate recurrences is an attractive alternative. It is feasible, is probably effective and minimizes the use of drugs, but compliance problems are common and protracted seizures are not always controlled. The subsequent management should include a risk profile approach considering a combination of risk factors for new FC rather than a single factor. By means of a risk index, based on simple clinical data including age at onset, family seizure history, seizure type and frequency of fever, children may be identified as being at low, intermediate or high risk for further febrile fits. However, risk factors for new FC and not for subsequent epilepsy should be used. It is concluded that preventing or abbreviating new FC with benzodiazepines appears to be a useful, although not ideal, drug-minimizing approach in managing many children with simple or complex FC. From a health hazard viewpoint, treatment is not strictly mandatory, although advisable. A selective strategy seems rational. Intermittent diazepam prophylaxis may preferably be offered to children at high risk for new FC.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1858482 TI - Experimental serotonin myopathy as an animal model of muscle degeneration and regeneration in muscular dystrophy. AB - Degenerating and regenerating muscle fibers, in serotonin-induced myopathy (SM) of rats, were investigated histochemically, immunohistochemically and electron microscopically with polyclonal antibodies against dystrophin, type IV collagen and laminin. The myopathy produced was characterized by grouping of degenerating and regenerating muscle fibers, and degeneration of capillary endothelial cells. Dystrophin disappeared in an early stage of muscle degeneration and reappeared in an early stage of regeneration. On the other hand, type IV collagen and laminin were well preserved throughout the degeneration and regeneration processes, even on the shrunk and wrinkled basement membrane of empty muscle fibers after phagocytosis. Muscle fiber regeneration was completed within each tube of the preserved basement membrane through the fusion of myoblasts derived from satellite cells of single necrotic fibers, myotubes already being visible on the 1st or 2nd day of regeneration on light microscopy. These small regenerating myotubes did not fuse with each other at all. The findings in the present experimental SM study are compatible with those in Duchenne muscular dystrophy, especially at the preclinical stage. PMID- 1858484 TI - Scrapie inoculation of mice: light and electron microscopy of the superior colliculi. AB - Ultrastructural examination of the superior colliculi of mice intraocularly inoculated with the ME7 strain of scrapie showed vacuolation early in the course of infection. Brains were examined between 85-260 days after monocular inoculation with scrapie. The mean incubation period for the development of clinical disease was 302 days. Vacuolation was seen initially in the contralateral superior colliculus and subsequently in the ipsilateral colliculus. In coded trials light microscopical vacuolation was seen from 218 days but ultrastructural examination showed that sparse vacuoles were inconsistently present in either or both of the ipsilateral and contralateral colliculi from 85 days; frequent vacuoles were seen from 190 days. Scrapie-induced vacuoles were differentiated from vacuoles present in control tissue by the presence of loculation or by a limiting double membrane which showed protrusion or proliferation of the innermost lamella. Vacuolation was seen in neuronal perikarya, myelinated fibres, dendrites and axonal presynaptic terminals. Vacuoles of myelinated fibres were observed within myelin and possibly also in the inner tongue of oligodendroglial cytoplasm. Whorled membrane configurations were also seen. Tubulovesicular particles, 40 nm in diameter, were recognised in two scrapie-infected mice. It is suggested that some scrapie vacuoles arise as a result of incorporation of abnormal membrane into organelles, possibly mitochondria, in neuronal perikarya and neurites and probably also within oligodendroglial cytoplasm and myelin. PMID- 1858483 TI - Transthyretin-type cerebral amyloid angiopathy in type I familial amyloid polyneuropathy. AB - To clarify the pathogenesis of cerebrovascular amyloid deposits, histological and immunocytochemical studies were performed on the central nervous system (CNS) in ten cases with type I familial amyloid polyneuropathy (FAP). They commonly suffered from peripheral somatic and autonomic nerve disorders without any CNS dysfunctions. However, all cases showed CNS amyloid deposits, mainly on the leptomeningeal vessels and pia-arachnoid membranes, with arteries and arterioles in the subarachnoidal space being the predominant site of cerebral amyloid accumulation. Using immunocytochemical staining methods with antibodies to amyloid beta-protein, human cystatin C and transthyretin (prealbumin), all of these amyloid deposits were specifically immunolabeled by the anti-human transthyretin antibody. However, there was no transthyretin-related amyloid deposits in the brain parenchyma. It is concluded that CNS transthyretin immunoreactive amyloid deposition with cerebral amyloid angiopathy (CAA) is a common pathological finding in this disease. Moreover, the patients with type I FAP are known to have an amyloid protein precursor (a variant of transthyretin) in serum. This transthyretin type of CAA, therefore, seems to be an example of cerebrovascular amyloid deposits derived from a serum precursor. PMID- 1858485 TI - Human ontogenesis. 3. Cell death in fetal muscle. AB - Naturally occurring muscle cell death in normal human fetal muscle was examined to determine the timing and structural differences with respect to muscle maturity. Two types of degenerative changes in developing muscle were found: cytoplasmic and nuclear. Degeneration of the primary and mature myotubes between 10 and 16 weeks of gestation entailed cytoplasmic condensation and disruption, swelling of mitochondria and dilatation of sarcoplasmic reticulum. In contrast, the formation of immature muscle fibres was associated with disintegration of satellite myofibres characterized by nuclear degenerative changes. These findings indicate that naturally occurring muscle cell death appears as a two-successive stage phenomenon of cell necrosis. Initially, at the myotube stage, a number of muscle cells are eliminated. In the later stage a single cell is removed from the cluster which seemingly is responsible for final shape and size of the muscle fibre. PMID- 1858487 TI - Phagocytosis of beta/A4 amyloid fibrils of the neuritic neocortical plaques. AB - Immunocytochemistry using monoclonal antibodies to beta/A4 protein was applied to study the macrophages involved in the removal of amyloid deposits. The material examined included necrotic brain tissue areas with abundant amyloid deposits collected from 32 autopsy cases. The beta/A4-immunoreactive products were found in numerous macrophages, appearing as early as 24 h after the onset of stroke. Immunogold electron microscope studies allowed us to localize the reaction product to the secondary lysosomes. Our study clearly demonstrates the differences between macrophages engaged in amyloid removal and microglial cells associated with amyloid deposits, which according to previous observations contain beta/A4 material within endoplasmic reticular channels. PMID- 1858488 TI - Postpartum depression and the experience of motherhood. PMID- 1858486 TI - Neuropathology of remote hypoxic-ischemic damage in the immature rat. AB - This study was undertaken to determine: (a) the duration of hypoxia required to produce brain damage in immature rats with unilateral carotid artery ligation (Levine technique); (b) the regions of immature brain most vulnerable to hypoxia ischemia (HI); and (c) the neuropathology of the remote HI insult. To this end, 7 day postnatal rats, subjected to unilateral carotid artery ligation combined with hypoxia of varying durations (45, 60, 75 or 90 min), were killed at 30 days of postnatal age and their brains examined by light microscopy. The results indicated that a longer duration of HI was more likely to produce brain lesions and that the extent and severity of the lesions closely correlated with the length of HI. Shorter intervals of HI primarily damaged the cerebral cortex and hippocampus, while longer periods resulted in more extensive damage and were often associated with cavitary lesions of the cerebral hemisphere. Comparison of HI brain damage produced by the Levine technique in immature and adult rats suggested that in immature rats: (a) the cavitary lesions were common; (b) the non-cavitary cortical lesions had a tendency to show a vertical band-like distribution - a pattern never seen in adults; and (c) the lesions often showed mineralization. The similarities between these experimentally produced HI cerebral lesions and those observed in the developing human brain, such as ulegyria and porencephaly, are discussed. PMID- 1858489 TI - Evaluation of symphysis-fundus measurements and weighing during pregnancy. AB - To evaluate the value of using symphysis-fundus (SF) distance and maternal weight gain measurements in predicting an infant's birth weight, these measurements were analysed in 831 single-birth deliveries at Aker University Hospital during a period of 3 months. Of the 96 babies with a birth weight below the 10th percentile for gestational age, 39 (41%) could be detected by a series of SF measurements. For every third correctly identified SGA (small for gestational age) baby, there were 7 false positive predictions. Only 13 (14%) of the mothers who gave birth to SGA babies demonstrated a weight gain at each medical check-up during pregnancy, whereas 197 (30%) of the women giving birth to normal-weight babies showed a weight gain each time (p = 0.02). However, for maternal weight gain, both predictive value (14%) and specificity (29%) were low. Hence, these two screening methods for the detection of SGA babies remain imprecise in practice. Test procedures should be improved, and factors influencing fetal growth should be emphasized to detect fetuses at risk. PMID- 1858490 TI - Sonographic dating of pregnancies among women with menstrual irregularities. AB - In order to study the benefit of sonographic dating, 277 women with irregular periods and 264 women with a scanty last bleeding had gestational age and estimated day of delivery (EDD) estimated from both last menstrual period (LMP) and measurement of fetal Biparietal Diameter (BPD) in the second trimester. For the women with irregular periods, the two estimates differed by more than 7 days for 51.6%, and more than 14 days for 25.6%. Corresponding figures for women with a scanty last bleeding were 44.3% and 21.6%, respectively. In general, the BPD estimates were better than the LMP estimates (P = less than 0.001) in predicting day of delivery, especially when the differences between the estimates exceeded 7 days. For women with irregular periods, post-term pregnancies decreased, from 20.2% according to the LMP estimate to 2.5% according to the BPD estimate. Corresponding figures for women with a scanty last bleeding were 16.7% and 4.5%, respectively. According to the LMP estimate, 64.8% of the women with irregular periods and 69.3% of the women with a scanty last bleeding gave birth within +/- 14 days of EDD. Corresponding figures for the BPD estimate were 83.6% and 88.3%, respectively. The conclusion is that sonographic dating of pregnancies among women with irregular periods and women with a scanty last bleeding substantially improve the accuracy of term prediction. PMID- 1858491 TI - Iontophoresis of vasoactive drugs. Effect on peripheral blood flow during pregnancy. AB - The aim of this study was to evaluate whether iontophoretic administration of the vasoactive agents noradrenaline (NA) and angiotensin (AII) combined with measurement of skin blood flow with a laser Doppler technique could serve as a predictive method for pre-eclampsia. Nine healthy non-pregnant women, 9 healthy pregnant women and 9 pre-eclamptic patients were investigated. A significant reduction of skin blood flow was induced by NA in all three groups and by AII in the non-pregnant group. There was no significant difference between healthy pregnant and pre-eclamptic patients in the degree of reduction of blood flow with respect to NA and AII administration. PMID- 1858492 TI - The relationship between granulocyte elastase-like activity of cervical mucus and cervical maturation. AB - Granulocyte elastase (elastase)-like activity in 119 samples of cervical mucus from pregnant women was measured. Though elastase-like activity in normal pregnant women was low in 2nd and 3rd trimesters (less than 20 units), it increased during labor (1st stage of labor: 70 +/- 50 U/l; 2nd stage: 72 +/- 56). Elastase-like activity in pregnant women with imminent premature delivery (24-30 gestational weeks) was also high (78 +/- 57). Elastase-like activity of cervical mucus correlated with Bishop score in both normal term and preterm labor. Elastase-containing granulocytes were identified by immunohistochemistry in ripened cervix in normal and preterm labor. Some granulocytes degranulate and release elastase into the cervical stroma. Others migrate through the basement membrane of the endocervix to reach the cervical canal. Elastase could not be demonstrated in immature cervix as assessed by Bishop score. The staining intensity of elastase in the cervix correlated closely with elastase-like activity in cervical mucus. Thus elastase-like activity in cervical mucus reflects the degree of cervical maturation. These results lead one to speculate that elastase is one of the neutral proteases which depolymerize and degrade collagen in the ripening cervix. PMID- 1858493 TI - Investigations into a possible immunological origin of idiopathic non-immune hydrops fetalis and initial results of prophylactic immune treatment of subsequent pregnancies. AB - The cause of the non-immune hydrops fetalis (NIHF) remains unsettled despite all efforts. From the immunological point of view of pregnancy as a successful course of an allograft, it would seem possible that the idiopathic NIHF can be caused by an immunologic disorder in the meaning of a host-versus-graft reaction. Of 324 cases of prenatally diagnosed NIHF, 49 (15.1%) could be classified after exclusion of all other causes as idiopathic and in 38 patients, as well as in 38 age- and parity-paired controls, a differentiation of HLA-antigens and a determination of lymphocytotoxic antibodies using the NIH Prolonged Incubations and Cold-Complement-Dependent Cytotoxicity Test (CoCoCy Test) were performed. In cases of idiopathic NIHF, the proportion of parents sharing 4 or 5 HLA antigens was increased significantly (p less than 0.05) compared with the control group. In women with idiopathic NIHF, the incidence of lymphocytotoxic antibodies was decreased, due to the test system used; between 28 and 68% in the NIHF group and 24-80% in the control group. The proportion of women without lymphocytotoxic antibodies was increased in the NIHF group by 72% to 52%, whereas in the control group, in none of the patients could a higher cytotoxicity with a lysing rate of more than 75% be detected. In 8 cases of idiopathic NIHF, where an increased paternal histocompatibility and a decreased incidence and percentage of lymphocytotoxic antibodies were determined, an immunotherapy was performed in order to induce maternal blocking antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858495 TI - Psychosocial indications for cesarean section. A retrospective study of 43 cases. AB - At Helsingborg Maternity Clinic the rate of elective cesarean section on psychosocial indications has increased. The purpose of this study was to identify and characterize those women requiring cesarean section despite the absence of obstetrical complications of pregnancy and childbirth and their reasons for doing so. Hospital case records from 1983 to 1987 were examined retrospectively. Nine women (20%) were primiparae, who for different reasons refused vaginal delivery; 34 (80%) were multiparae, half of whom (n = 17) had been delivered previously by an unanticipated cesarean section and 4 women by elective cesarean. Seven women had experienced obstetrical complications during vaginal delivery. Five had a diagnosis of other serious medical conditions during the previous or the present pregnancy. The final parous woman demanded a cesarean in spite of perfect health and a normal previous delivery. The patients' reasons for demanding a cesarean, as understood from hospital records, were primarily a very serious fear of childbirth. A psychotherapeutically trained member of the obstetrical staff is well equipped to offer help. The impact of previous complicated birth is obvious in this study. Hopefully, we can avoid some future cesarean sections by means of better care for patients in crisis resulting from complicated childbirth. PMID- 1858494 TI - Vacuum aspiration for termination of early second trimester pregnancy after treatment with vaginal prostaglandin. AB - Vaginal and intramuscular administration of prostaglandin analogues are routinely used for dilatation of the cervical canal prior to vacuum aspiration in first trimester abortion. Whether the same procedure is also useful during the first weeks of the second trimester has been much less investigated. In the present study, 127 women in the 13th and 14th week of pregnancy were pretreated with 3 mg 9-deoxo-16,16-dimethyl-9-methylene PGE2 administered vaginally 12 hours before surgery. At surgery the cervical canal was dilated to 9.8 mm +/- 2.5 mm (mean +/- SD) and the evacuation of the uterus was uneventful. In 21% of the patients vaginal bleeding occurred prior to the operation. The mean blood loss at surgery was 49 ml and exceeded 100 ml in only 6 patients. Gastrointestinal side effects were rare but analgesic injections were demanded by 29% of the patients during the pretreatment period. No subsequent curettage was performed during the follow up period but 2 patients (1.6%) were readmitted because of post-abortion endometritis. It can be concluded that after pretreatment with PG, vacuum aspiration can be safely performed during the first weeks of the second trimester. PMID- 1858496 TI - Acta seventy years ago. The very first issue. PMID- 1858497 TI - The effect of mediolateral episiotomy at delivery on pelvic floor muscle strength evaluated with vaginal cones. AB - In a prospective study, pelvic floor muscle strength was investigated pre- and post partum in 87 women with uncomplicated pregnancies. Those vaginally delivered were 71 primiparas, while 16 underwent an elective cesarean section. The objective was to evaluate the effect of the delivery procedure on the pelvic floor muscle strength with the aid of vaginal cones. In the group of women with vaginal delivery three subgroups were identified: episiotomy, spontaneous laceration and intact perineum. Pelvic floor muscle strength was weakest in the episiotomy subgroup, the difference in values between this subgroup and each of the other subgroups and the elective cesarean section group being significant. No significant difference was evident between the spontaneous lacerations and intact perineum subgroups. PMID- 1858498 TI - Maternal factors associated with high birth weight. AB - Maternal characteristics associated with high birth weight were studied in 473 mothers delivered of singleton infants at term with a birth weight of 4500 g or more. The controls were mothers who gave birth to singleton infants at term, with a normal birth weight +/- 1 SD for Swedish newborns. In the multivariate analysis the maximum symphysis-fundus height measurement and gestational duration were strongly significant (p less than 0.001), after correction for other variables, for the probability of being delivered of an infant of high birth weight. Maternal height, weight at beginning of pregnancy, total gestational weight increase and previous live birth of an infant weighing greater than or equal to 4500 g were also important (p less than 0.05) for high birth weight. The maternal characteristics included were evaluated in a prognostic model. With symphysis fundus height measurement included, the sensitivity increased from 80.3 to 83.3% and specificity from 78.8 to 85.6%, compared with a model where symphysis-fundus measurement was not available. PMID- 1858499 TI - Sexual experience, abortion and sexually transmitted diseases among young women at a contraceptive clinic. AB - All visitors who during one year visited a contraceptive clinic in the Solna district of Stockholm County and were below the age of 26 were asked to fill in a questionnaire and offered a test for C. trachomatis. Three hundred and six women (97%) participated. Ninety percent had at some time used oral contraceptives and 91% had experience of condom use. One-fifth of the whole group had undergone one or more legal abortions, and one fourth had experience of a sexually transmitted disease (STD). The most common STD experienced was chlamydia, followed by condyloma. The actual prevalence of chlamydia in the group was 6%. Sexual contacts were often made early in on-going steady relations. Forty-two percent admitted casual sex, but the number of life-time partners was five or less among the majority. PMID- 1858500 TI - Treatment of candidal vaginitis. A prospective randomized investigator-blind multicenter study comparing topically applied econazole with oral fluconazole. AB - Two hundred and thirty-five women with clinically and microbiologically proven candidal vaginitis were randomly allocated for treatment with either one topically applied vaginal tablet of 150 mg econazole (114 women) or one orally administered capsule of 150 mg fluconazole (121 women). The women returned for follow-up visits 7-10, 28-35, and 80-100 days after the recruitment visit. Women with clinical and/or mycological failures and/or a recurrence were successively excluded from the follow-up. At the 28-35-day follow-up visit, the women treated with fluconazole had a significantly higher clinical/microbiological cure rate than those given econazole (P = 0.022; Fisher's exact 2-tail test). No significant such differences were observed at the 7-10 and the 80-100-day follow up visits, although fluconazole tended to be more efficacious. Nine women administered fluconazole, and 2 women given econazole reported minor systemic side effects of the treatment. Three women out of 4 preferred oral to local therapy of candidal vaginitis. PMID- 1858501 TI - Iron supplementation during pregnancy. AB - 192 pregnant women were consecutively randomized to either a vitamin-mineral pill or a vitamin mineral pill with a high iron content in a prospective, open, randomized investigation. The participants were advised about iron-rich foodstuffs twice during pregnancy. Iron status of the mother proved to be without any significance for the outcome of pregnancy. A serum ferritin level of 80 pmol/l in mid-pregnancy followed by a control in the last trimester was suggested as a guide in deciding of whether or not to prescribe supplementary iron during pregnancy. PMID- 1858502 TI - Edrophonium chloride for testing colonic contractile activity in man. AB - The effects of cholinergic stimulation on the entire human colon are at present relatively unknown. For this reason, we evaluated the influence of a short-lived anticholinesterase agent, edrophonium chloride, on proximal and distal colonic contractile activity in man. Eight healthy volunteers of both sexes were studied with a multi-lumen manometric probe positioned with the aid of a colonoscope. Recordings were then obtained 30 minutes pre- and post-drug administration. Edrophonium chloride (10 mg intravenous) significantly stimulated both proximal and distal colonic contractile activity, and the maximum increase was observed within 10 minutes following injection, although some differences were observed between colonic segments in response to the drug. No important side effects were complained of after edrophonium. Due to the potent stimulatory property on colonic smooth muscle, to its short duration of action, and to the paucity of side effects, it is concluded that edrophonium chloride may be useful as a stimulating substance during manometric investigations of the human colon. PMID- 1858503 TI - Effects of endothelin on renal haemodynamics and segmental sodium handling in conscious rats. AB - The effects of endothelin (100 and 600 pmol/kg) on renal plasma flow (RPF), glomerular filtration rate (GFR), sodium excretion (UNa V) and segmental sodium handling were investigated in conscious rats. Low-dose endothelin decreased renal plasma flow by 26% without affecting glomerular filtration rate and sodium excretion. High-dose endothelin reduced renal plasma flow, glomerular filtration rate, sodium excretion and lithium clearance by 57, 45, 38 and 52%, respectively. The fall in sodium excretion was not due to a direct effect of endothelin on tubular sodium transport since sodium excretion corrected by glomerular filtration rate and fractional proximal and distal sodium reabsorption did not change throughout the study. These results indicate that the impairment in renal perfusion is responsible for the antinatriuretic effect of endothelin in conscious rats. PMID- 1858504 TI - Potent vasoconstrictor effects and clearance of endothelin in the human forearm. AB - The vascular effects of endothelin-1 in humans were investigated by infusion into the brachial artery of healthy volunteers. Endothelin-1 (5-500 pmol min-1) evoked potent and long lasting increase in forearm vascular resistance (FVR) and reduction in venous compliance, suggesting constriction of both resistance and capacitance vessels. The threshold for effect on forearm vascular resistance was at a calculated plasma concentration of 614 pmol 1-1. Endothelin-1 was on a molar basis 10-20 times more potent than noradrenaline as constrictor of both resistance and capacitance vessels. The increase in forearm vascular resistance induced by endothelin-1 lasted more than 30 min and that by noradrenaline less than 3 minutes. The endothelin-1-like immunoreactivity collected in the venous effluent during the infusion was 10-26% of the calculated arterial plasma concentration, indicating local removal of endothelin. After the infusion of endothelin-1 the urine concentration of prostacyclin metabolite increased significantly, indicating release of prostacyclin, whereas the concentration of thromboxane metabolite did not increase. It is concluded that endothelin-1 is a highly potent constrictor of human resistance and capacitance vessels, that it causes release of prostacyclin and that circulating endothelin-1 is efficiently removed by the forearm in vivo. PMID- 1858505 TI - Regional extraction of endothelins and conversion of big endothelin to endothelin 1 in the pig. AB - Endothelin-like immunoreactivity (ET-LI), mean arterial blood pressure (MABP) and vascular resistance in the spleen, kidney and femoral vascular bed were measured during intravenous infusions (20 pmol.kg-1.min) of endothelin-2 (ET-2), endothelin-3 (ET-3), big endothelin-1 (big ET) and sarafotoxin 6b in the pig. All peptides (especially endothelin-2 and sarafotoxin 6b) caused vasoconstrictor effects in the kidney. Endothelin-2, endothelin-3 and sarafotoxin 6b also evoked significant increases in splenic and femoral vascular resistance. The relative vasoconstrictor response to endothelin-2 was larger in the kidney and spleen than in the femoral vascular bed whereas the opposite was observed for endothelin-3. A high degree of plasma clearance for endothelin-like immunoreactivity was observed. Thus, for ET-2 and ET-3 about 70% of arterial endothelin-like immunoreactivity was removed over the kidney while over the spleen and femoral vascular bed an extraction of 50% for plasma endothelin-2 and 30-40% for endothelin-3 was observed. Big endothelin-1 was only extracted by 34% over the kidney and not at all in the splenic or femoral vascular bed. The metabolic plasma half-lifes of endothelin-2 and endothelin-3 in vivo were in the same range, 1-2 minutes, whereas the half-life of big endothelin-1 was 9 minutes. HPLC characterization of the plasma endothelin-like immunoreactivity during and after big endothelin-1 infusion as well as measurements using a specific endothelin-1 antiserum revealed formation of endothelin-1 from circulating big endothelin-1 in vivo but not in plasma in vitro. It is concluded that there exists specificity concerning the vasoconstrictor effects and the removal of endothelin-peptides from the circulation, both mechanisms being most prominent in the kidney. Big endothelin-1 has a much longer metabolic half-life, less regional clearance and poor vasoconstrictor activity compared with endothelin-1. Furthermore, endothelin 1 is formed from circulating big endothelin-1 probably by an endothelin converting enzyme. PMID- 1858507 TI - Dual response from human muscle spindles in fast voluntary movements. AB - Single-unit impulses were recorded from the radial nerve of attending human subjects using the microneurography technique. The discharge of muscle spindle afferents from the extensor digitorum muscles was analysed while subjects performed fast lengthening and shortening voluntary movements as well as movements of moderate speed at a single metacarpophalangeal joint. Opposing or assisting loads of moderate size were added in some tests. Fast lengthening movements were, in practically all units, associated with acceleration of spindle discharge. However, the responses were modest and in many primary afferents it was of similar size as their response to small irregularities during slower movements. During shortening movements, most spindle afferents stopped firing altogether, whereas some afferents exhibited a distinct burst of impulses at the onset of active shortening followed by silence during the main part of the movement. This initial shortening responses was sometimes more prominent when the parent muscle worked against an opposing load. It was interpreted as a result of fusimotor drive associated with the building up of force in the contracting muscle. The initial shortening response from the contracting muscle and the stretch response from the antagonist constitute a dual signal, describing accurately the onset of joint movement as seen from the two muscles. It remains to be clarified which role this pattern of afferent responses may have in the design of the current motor output and in the capturing of nature and size of the external load. PMID- 1858506 TI - Protective role of sympathetic nerve activity to exercising skeletal muscle in the regulation of capillary pressure and fluid filtration. AB - This study describes the integrated sympathetic/metabolic control of capillary pressure (Pc) and filtration in cat skeletal muscle as studied during graded exercise and superimposed graded (2, 6 and 16 Hz) vasoconstrictor nerve excitation. The applied technique permitted simultaneous analysis of the underlying changes of resistance in the whole vascular bed (RT) and in its large bore arterial resistance vessels (greater than 25 microns), small arterioles (less than 25 microns) and veins. Graded exercise per se caused graded increases in capillary pressure, which at heavy work exceeded the resting control value by 12.2 mmHg, in turn leading to marked loss of plasma fluid by filtration. Sympathetic nerve stimulation was much more efficient in lowering capillary pressure during exercise than at rest, in spite of an exercise-induced marked attenuation of the vasoconstrictor response (RT). The sympathetically evoked capillary pressure fall per unit resistance increase was larger the greater the degree of exercise vasodilation, implying a highly nonlinear relation between capillary pressure and RT and also between the more direct determinant of capillary pressure the post- to precapillary resistance ratio, and RT. Strenuous exercise in vivo is known to be associated with a markedly increased reflex sympathetic discharge to exercising muscle which has been a puzzling feature in view of its untoward restriction of the exercise hyperaemia response. To the extent the present results are representative for this in vivo situation, they suggest that sympathetic discharge to exercising muscle, in spite of some flow restricting effect, might serve a highly beneficial function, causing effective protection against excessive work-induced rise of capillary pressure and harmful plasma fluid loss into the extravascular space of working muscle. PMID- 1858508 TI - Lactate transport in skeletal muscle cells: uptake in L6 myoblasts. AB - During exercise, lactate is produced by degradation of glucose-6-phosphate during glycolysis in the contracting muscles. This lactate is metabolized during and after exercise in the muscle itself and also in the liver and other muscles, which can use it as an energy metabolite or can resynthetize glycogen. Lactate is transported in the blood, and the rate of muscular utilization may be limited by two factors: the rate of metabolic utilization by the muscle cell; and the rate of transport across the membrane regulating lactate transfer from the blood to the cell. We have studied lactate uptake in L6 muscle cells by incorporation of 14C-lactate. The uptake rates were linear for 20 seconds with 5 mM lactate and 10 seconds with 20 mM. The uptake during 10 seconds for physiological lactate concentrations (1-20 mM) gave a straight line passing through the origin. Lactate uptake was not altered by specific inhibitors of lactate transport (2.5 mM alpha cyano-4-hydroxycinnamic acid. 5 microM 4,4'-diisothiocyanostilbene 2,2'disulphonic acid) or by the stereospecific D-lactate inhibitor. The results suggest that L-lactate uptake in L6 cells occurs by passive diffusion. PMID- 1858509 TI - Mechanical properties of isolated human oesophageal submucosal veins. AB - The mechanical properties of isolated human oesophageal submucosal veins were investigated. The veins were without tone or spontaneous activity and possessed a high compliance, tolerating a stretch of several hundred per cent of the length at which the vessels were first able to contract with only minor increases in passive tension. The veins were capable of producing active tension when the length exceeded 30% of L0 (the length at which maximum wall tension (T0) was developed when activated by 124 mM K(+)-solution). The veins from the oesophageal body (OB) had a higher L0 than the veins from the gastrooesophageal junction (GOJ) (1180 microns vs 820 microns) and T0 was correspondingly higher (1.1 mN/mm vs. 0.6 mN/mm). However, there was no significant difference in the calculated effective transmural pressure (P) at the two locations. Noradrenaline induced contractions in all preparations tested with a maximum response equivalent to the tension achieved after stimulation with 124 mM K(+)-solution, pD2 values for noradrenaline in vessels from the oesophageal body and the gastroesophageal junction were 7.03 +/- 0.28 (mean +/- SEM) and 7.15 +/- 0.20, respectively. The present model seems suitable for future studies of human oesophageal submucosal veins from the oesophageal body and the gastrooesophageal junction. PMID- 1858510 TI - Left ventricular responses to experimental aortic coarctation in growing puppies. AB - The haemodynamic status of 8 coarctated and 7 sham-operated beagle puppies was studied by a catheterization technique at rest and during isoproterenol and volume loading at the ages of 7 (I) and 9 (II) months (5 and 7 months after the experimental coarctation). Proximal aortic systolic and pulse pressures were constantly higher in the coarctation group than in the control group (P less than 0.05), and the systolic pressure gradient across the coarctation was always significantly higher in the coarctation group [I at rest mean 45 +/- 5 (SD) vs 5 +/- 4 mmHg, P less than 0.001, and after I isoproterenol infusion 56 +/- 9 vs 10 +/- 6 mmHg, P less than 0.001, and after I dextran infusion 58 +/- 10 vs 8 +/- 7 mmHg, P less than 0.001]. The time constant of exponential isovolumic left ventricular pressure fall after the isoproterenol tests was longer in the coarctation group (I 28 +/- 8 ms and II, 30 +/- 4 ms) than in the control group (I, 21 +/- 2, P less than 0.05 and II, 19 +/- 3 ms, P less than 0.005), indicating impaired relaxation. The tension time index during the volume loading tests increased in the coarctation dogs (I, 4150 +/- 660 and II, 4080 +/- 810 mmHg s min-1) to higher levels than in the control group (I, 3550 +/- 220, II, 2540 +/- 1140 mmHg s min-1, P less than 0.05 both). Cardiac output, left ventricular end diastolic pressure, inotropic parameters and heart rate were similar in both groups during the infusions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858511 TI - Respiratory sinus arrhythmia is reversed during positive pressure ventilation. AB - In order to study the relationship between heart rate and depth of anaesthesia, respiratory sinus arrhythmia (RSA) was investigated during enflurane and isoflurane anaesthesia in 28 patients (15-39 years). Positive pressure ventilation (six breaths min-1) was used. Respiratory sinus arrhythmia was evaluated during light anaesthesia, deep anaesthesia (burst suppression in EEG) and light anaesthesia again by using signal averaging technique. In most patients, decrease of the heart rate was seen during inspiration (positive tracheal pressure), and increase during expiration. Respiratory sinus arrhythmia did not disappear in deep anaesthesia. Inter-individual variation in the magnitude and phase relationship of respiratory sinus arrhythmia was considerable, and was not associated to the level of anaesthesia. PMID- 1858512 TI - Stimulation of airway ciliary motility by immunologically activated canine pulmonary macrophages: role of leukotrienes. AB - To elucidate a possible interaction between alveolar macrophages and airway epithelial cells in allergic conditions, we studied the effect of immunologically stimulated macrophages on ciliary beat frequency (CBF) of cultured canine tracheal epithelium by a photoelectric method. Administration of supernatants from macrophages incubated with anti-dinitrophenyl (DNP) IgE antibody and anti dinitrophenyl-human serum albumin dose-dependently increased ciliary beat frequency, the maximal increase from the baseline being 30.4 +/- 5.0% (mean +/- SE, P less than 0.01), an effect that was accompanied by the release of leukotriene (LT) C4 and leukotriene D4. This ciliostimulation was not affected by pretreatment of macrophages with indomethacin but was inhibited by that with nordihydroguaiaretic acid. Addition of FPL 55712 abolished the response of ciliary beat frequency to the stimulated macrophages, and exogenously administered leukotriene C4 and leukotriene D4 dose-dependently increased ciliary beat frequency. These results suggest that macrophages increase respiratory ciliary motility through the IgE-mediated release of leukotrienes and may modulate mucociliary transport function in the airway. PMID- 1858513 TI - The efflux of 86Rb and [3H]5-HT from human platelets during continuous perfusion: effects of potassium-induced membrane depolarization and thrombin stimulation. AB - In order to study the ionic efflux or granule release from human platelets following pulse exposure to various stimuli, a method for continuous perfusion of platelets was developed. The method was applied to compare the effects of membrane depolarization and thrombin stimulation on the release of 86Rb and [3H]5 HT. Washed and preloaded human platelets were placed on a membrane filter in a temperature controlled polypropylene chamber, and subsequently perfused with buffer. After an initial washout period the efflux of 86Rb or [3H]5-HT reached steady, low levels. K+ induced concentration dependent increases in 86Rb efflux, corresponding to a depolarization of the membrane potential, whereas the efflux of [3H]5-HT was unaltered. Thrombin induced concentration dependent increases in the efflux of both 86Rb and [3H]5-HT. Pretreatment with K+ 12 or 30 mM did not alter the [3H]5-HT efflux induced by thrombin 0.1 U ml-1. Scanning electron micrographs of platelets on the filter showed that the unstimulated platelets had regular shape, whereas after addition of thrombin there was formation of pseudopods and minor aggregates. The effect of potassium-induced membrane depolarization on platelet aggregation was also studied. High concentration of K+ did not induce aggregation or shape change during 2 or 10 minutes of incubation. K+ had little or no effect on aggregation induced by ADP 2 microM or thrombin 0.4 U ml-1. The results from release experiments and aggregation tests argue against an immediate coupling between membrane potential and platelet reactivity. PMID- 1858515 TI - Does chronic hypoxaemia induce transformations of fibre types? AB - The study comprised nine patients with chronic obstructive lung disease. Quadriceps muscle biopsies were studied with respect to fibre type composition before and after haemodilution that brought haemoglobin (Hb) to within normal limits. Ten days elapsed between the two biopsy occasions. The arterial oxygen tension (PaO2) and saturation (SaO2) were depressed to 8.4 +/- 2.0 kPa and 89 +/- 11% in the patients with chronic obstructive lung disease and increased to 9.2 +/ 2.1 and 91 +/- 8% with haemodilation. The type II fibre proportion was 71 +/- 12% before haemodilation and significantly higher than normal (reference group, see Aniansson et al. 1981). Following haemodilation the proportion of type II fibres decreased significantly to 60 +/- 14%. The proportion of type II fibres was directly related to the haemoglobin content before, but not after, haemodilation and was inversely related to PaO2 and SaO2 both before and after haemodilation. In conclusion, hypoxaemia may be a factor underlying the high proportion of type II fibres found in patients with chronic obstructive lung disease. PMID- 1858514 TI - Mechanism of anoxic conduction block in mammalian nerve. AB - The mechanism by which anoxia blocks impulse conduction was studied in isolated sciatic nerves from the rat. The desheathed nerve was mounted in a recording chamber, and the compound action potential (CAP) was measured at controlled temperature (23 and 37 degrees C). When the nerve was irrigated with nitrogenated Ringer's solution compound action potential decreased to 50% in 10 min at 37 degrees C and in 35 min at 23 degrees C, whereas in oxygenated solution compound action potential decreased less than 5% in 60 min. A Na-free nitrogenated solution similarly caused anoxic block, that is the effect was independent of impulse activity. Ouabain (1 mM) decreased compound action potential by only ca. 4% in 30 min, and the effect of anoxia was delayed in presence of ouabain. Dinitrophenol (0.05 mM) reduced compound action potential to 50% in 5 min. These findings indicated that the anoxic block was not related to changes in axonal concentration of Na or K following impulse activity or inhibition of Na-K-ATPase. Instead the findings imply that the anoxic block is due to inactivation of Na channels as a consequence of inhibition of another ATP-dependent process in the axon. PMID- 1858516 TI - L-NG-nitro arginine inhibits non-adrenergic, non-cholinergic relaxation of human isolated corpus cavernosum. PMID- 1858517 TI - Cecropin P1-like immunoreactivity in epithelial cells of duodenum and glucagon cells of the pancreas. PMID- 1858518 TI - Androgen treatment prevents loss of cancellous bone in the orchidectomized rat. AB - This report describes histomorphometric evidence for an important role of androgens in maintaining cancellous bone balance at a remodeling site in vivo. Rats were orchiectomized (ORX) at 7 weeks of age and received either androgens or vehicle 1 week later (testosterone, 1-dehydrotestosterone, or 5 dihydrotestosterone) by subcutaneous pellet, producing controlled release of the drug for 3 weeks. Intact male rats and untreated ORX animals served as controls. After 4 weeks untreated ORX resulted in undetectable serum testosterone levels and marked atrophy of seminal vesicles compared with intact controls. Histomorphometry revealed severe cancellous osteopenia in the secondary spongiosa of the proximal tibial metaphysis. The length of bone surface lined by apparently "active" osteoblasts and number of osteoclasts per length of cancellous bone surface were increased following ORX. Testosterone treatment at 5 mg (per 21 days) produced subphysiologic serum testosterone levels. In contrast, 10 and 25 mg pellets resulted in serum testosterone ORX, and the degree of protection was dose dependent. 1-Dehydro- and 5-dihydrotestosterones displayed a bone-protective effect similar to that of testosterone. The results demonstrate that gonadal insufficiency results in a cancellous osteopenia that is preventable by testosterone treatment. Further, because a similar protective action was achieved using the nonaromatizable androgen 5-dihydrostestosterone, the results suggest that this bone-sparing effect is mediated by androgen rather than by metabolism of the androgen to an estrogen. PMID- 1858519 TI - Smoking and bone loss among postmenopausal women. AB - We examined the effect of smoking on bone mineral density (BMD), rates of bone loss, and fractional whole-body retention of 47Ca in healthy postmenopausal women enrolled in a 2-year calcium supplementation trial. Bone density was measured by single- and dual-photon absorptiometry. BMD of the radius at the study baseline was inversely related to pack-years of exposure when controlled for body mass index and years since menopause (partial r = -0.18, p = 0.05, n = 125). The adjusted mean (+/- SD) annualized rate of bone change from the radius was greater among smokers than nonsmokers (-0.914 +/- 2.624%/year, n = 34, versus 0.004 +/- 2.568%/year, n = 278, respectively; p = 0.05). Similar trends were observed at the femoral neck, os calcis, and spine. Rates were were adjusted for caffeine intake, alcohol use, supplement type, and, at the spine only, menopausal status. At entry into the trial higher serum levels of alkaline phosphatase and lower levels of total and ionized calcium were found in smokers compared to nonsmokers. These differences did not persist with supplementation. In 44 women studied fractional 47Ca retention was lower in the 8 smokers than the 36 nonsmokers (16.6 versus 19.1%, respectively; p = 0.03). These results demonstrate an increased rate of bone loss at the radius after menopause and suggest that smoking is associated with decreased calcium absorption. PMID- 1858520 TI - The bisphosphonate alendronate (MK-217) inhibits bone loss due to ovariectomy in rats. AB - Estrogen deficiency in mammals is known to increase bone turnover and result in reduced bone mass. The bisphosphonate, 4-amino-1-hydroxybutylidene-1,1 bisphophonic acid disodium salt, alendronate (MK-217), is a potent inhibitor of bone resorption and was evaluated in this study for its ability to inhibit bone loss following ovariectomy in rats. Alendronate was administered sc in doses of 0.0, 0.056, 0.28, 1.40, and 7.0 mg P/kg/month, divided into two, four, or eight monthly subcutaneous injections for each dose, to female Sprague-Dawley rats (250 280 g) that underwent bilateral ovariectomy. Rats were sacrificed 12 weeks postovariectomy, the femora ashed, and the tibiae prepared for static and dynamic histomorphometric analyses. Femoral bone mass in vehicle-treated rats was reduced by 12% 12 weeks after ovariectomy compared to the nonovariectomized control group. In MK-217-treated rats femoral bone mass was significantly increased in a dose-dependent manner compared to either ovariectomized or nonovariectomized controls. Histomorphometric analysis showed significant increases in tibial trabecular bone volume with no decrease in osteoclast number. Doses delivered twice per month or eight times per month were equally effective in achieving the peak bone volume 12 weeks after ovariectomy. In conclusion, alendronate (MK-217) was effective in inhibiting bone loss due to estrogen deficiency in rats, and the magnitude of its effect was related primarily to the total amount of compound administered rather than the frequency of its administration. PMID- 1858521 TI - Effect of chronic carbonic anhydrase inhibitor therapy on bone mineral density in white women. AB - A limited, dual-photon absorptiometry, single-center study of bone mineral density (BMD) was conducted on white female glaucoma subjects who were chronic users of the carbonic anhydrase (CA) inhibitors acetazolamide (Az) or methazolamide (Mz). In postmenopausal subjects long-term (greater than 4 years) CA inhibitor use was associated with a bone-sparing effect as judged by spinal BMD in comparison to controls matched for age, sex, weight, and ethnic group or in comparison to a national normative data base. Short-term (0-2 years) postmenopausal CA inhibitor users and premenopausal subjects using CA inhibitors showed no sparing of spinal BMD. Femoral neck BMD was not affected by CA inhibitor therapy in any of the groups. This study supports a proposed role for carbonic anhydrase in human bone resorption and suggests a possible future utility for carbonic anhydrase inhibitors in prophylaxis or management of primary involutional osteoporosis. Future studies are necessary to verify and expand these findings, assess the effects of CA inhibitors on bone mechanical competence, and further develop CA inhibitors with some specificity for bone. PMID- 1858522 TI - Isolation of avian osteoclasts: improved techniques to preferentially purify viable cells. AB - Among the many different methods that have been used to obtain and study isolated osteoclasts from a variety of species, the egg-laying hen maintained on a low calcium diet has proven to be one of the richest sources of relatively large numbers of osteoclasts. However, recent reports and our own observations indicate that only a very small proportion of the osteoclasts harvested by such methods are viable. The difficulty in obtaining large numbers of viable osteoclasts has restricted studies of osteoclast function and regulation, and so new isolation methods were sought. This report describes an osteoclast isolation procedure designed to substantially enrich for large numbers of viable authentic osteoclasts. Size and cell density differences between osteoclasts and contaminating mononuclear cells have been exploited in developing the methods for osteoclast enrichment. Sequential nonenzymatic and enzymatic procedures, followed by cell density separations, have yielded three populations of osteoclasts derived from chick hatchlings maintained on a low-calcium diet. A corresponding decrease in bone-associated osteoclasts during the sequential isolation scheme has been monitored using an osteoclast-directed monoclonal antibody, 121F. The first two populations contain 40% osteoclasts, which are predominantly (greater than 99%) nonviable, but the third population contains 8-fold more viable osteoclasts, effectively increasing the proportion of viable osteoclasts more than 25-fold in comparison with the first two populations. The osteoclast-like nature of the isolated viable population 3 cells was established by demonstrating ruffled border formation, possession of the 121F monoclonal antibody-reactive osteoclast antigen, bone particle resorption activity, and resorption pit formation on cortical bone slices revealed by transmission and scanning electron microscopy. PMID- 1858523 TI - A systemic acceleratory phenomenon (SAP) accompanies the regional acceleratory phenomenon (RAP) during healing of a bone defect in the rat. AB - The rate of remodeling in the region of a bone defect exceeds normal tissue activity. It was Frost who described this reaction as a regional acceleratory phenomenon (RAP). We investigated the local healing process with rats with a burr hole defect (1.2 mm in diameter) in the left tibia. We differentiated an initial phase of bone formation followed by a phase of predominant resorption. To determine whether this regional enhancement of bone formation would result in a systemic impact on bone metabolism, we analyzed both tibiae and femora and the fourth lumbar vertebra. On day 7 both femora of rats with the tibial defect showed a significant increase in computerized x-ray density, dry weight, ash weight, and Ca2+ content. Both tibiae and the fourth lumbar vertebra showed a significant increase in mineralizing surface, mineral apposition rate, and bone formation rate. Because of these results we conclude that a systemic acceleratory phenomenon (SAP) accompanies the RAP. SAP affects only the cancellous, but not the cortical bone compartment. SAP is associated closely with the occurrence of woven bone during the formation phase of the healing process. Thus we assume that woven bone formation plays a pivotal role in the mediation of SAP. PMID- 1858524 TI - Comparison of dual-photon absorptiometry systems for total-body bone and soft tissue measurements: dual-energy X-rays versus gadolinium 153. AB - A total of 81 subjects (41 males and 40 females) were scanned by dual-photon absorptiometry by 153Gd source (DPA; Lunar DP4) and by dual-energy x-ray absorptiometry (DEXA; Lunar-DPX) within a 24 h period. Total-body bone mineral density (TBMD), calcium content (Ca), and soft tissue mass (ST) were determined with a precision of about 1-1.5% using DPA and 0.5-1.0% using DEXA. Measurements of TBMD, Ca, ST, bone area (area), percentage fat, and regional bone mineral densities (BMD) were compared. Paired t-tests showed small but significant differences between all measurements. Correlations (r) for TBMD, Ca, area, ST, percentage fat, arm BMD, leg BMD, and trunk BMD were 0.99, 0.99, 0.97, 0.99, 0.97, 0.99, 0.99, and 0.98. There were small systematic differences for TBMD (less than 1%), calcium (3%), bone area (3%), soft tissue mass (7%), and percentage fat (9%) between the two approaches. Regression equations are given relating these measurements. PMID- 1858525 TI - Measurement of mechanical properties of bone material in vitro by ultrasound reflection: methodology and comparison with ultrasound transmission. AB - An ultrasound reflection technique was designed and implemented to study the mechanical properties of bone material. The technique uses the fact that an ultrasound beam produced in water undergoes total internal reflection off a bone sample at a critical angle formally related to the velocity of a pressure wave in bone. When the plane of scattering is rotated around the normal to the sample surface, the critical angle varies with a periodic dependence dictated by the intrinsic symmetry of the bone structure at the point being examined. Most current measurements of sound velocity are made using transmission techniques. A double-blind intercomparison between this technique and a transmission technique, which was previously validated against tensile mechanical testing, was performed for samples of isotropic materials and of human cortical bone. Strong correlations were found for both sets of samples. For the isotropic materials the velocities were approximately equal, but for bone they were on average 11% higher in reflection than in transmission. This was the result both of the higher frequency employed in reflection (3.5 rather than 2.25 MHz) and of the different effects of sample imperfections on the two measurements. In particular, the reflection technique used in this work studied the surface of the sample, but the ultrasound beam in the transmission method propagated through its interior. In assessing the mechanical properties of bone specimens by ultrasound, the reflection technique samples a discrete bone surface element and the transmission method analyzes the entire volume of the specimen. Thus the reflection technique may yield a measure of the mechanical property of bone trabeculae that is largely unaffected by the mass of the entire specimen, but mass and the structural density of the specimen affect the transmission method. PMID- 1858526 TI - Thirteenth annual meeting of the American Society for Bone and Mineral Research. San Diego, California, August 24-28, 1991. Program and abstracts. PMID- 1858527 TI - Acetazolamide reactivity on cerebral blood flow in patients with subarachnoid haemorrhage. AB - Cerebral vasodilatory capacity was evaluated by acetazolamide-activated N isopropyl-p-[123I]iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) in 42 patients with subarachnoid haemorrhage (SAH). A low perfusion area was present in the corresponding region of haematoma seen on the CT and continued to be noted throughout the time courses. Deteriorated acetazolamide reactivity affected by surgical intervention was seen in 100% of the patients who underwent aneurysm repair in the 1st postoperative week, 92% in the second week, 73% in the third week, and 47% in the fourth week. Three patients with acute diffuse brain swelling seen on CT showed intracranial non filling of 123I-IMP on SPECTs performed on Day 6, and all three died by Day 10. Some low perfusion areas, due to probable vasospasm, were present in 77% of Hunt and Hess grades I and II patients and in 100% of grades III, IV, and V patients throughout their time courses. Overall, low perfusion areas, due to probable vasospasm, were seen in 10 patients (31%) of 32 who underwent SPECT between Day 4 and 8,23 (77%) of 30 between Day 9 and 14, 21 (72%) of 29 between Day 15 and 21, and 11 (48%) of 23 between Day 22 and 28. The results suggest acetazolamide activated 123I-IMP study is of value in evaluating changes in vasodilatory capacity in SAH patients in the acute and subacute stages. PMID- 1858528 TI - Modulation by interferon alpha of the decreased natural killer activity in patients with glioblastoma. AB - It is known that natural killer (NK) cells are involved in immunosurveillance against tumours. This study examines the NK activity of mononuclear cells (MNC) from the peripheral blood of patients with glioblastoma. The cytotoxic inducer effect of interferon-alpha (IFN-alpha) upon these MNC has also been studied. A marked decrease in NK activity mediated by MNC from these patients was found. This functional defected in MNC is not due to a decrease in phenotypically defined NK cells. After long-term (5-day) incubation with IFN-alpha, MNC from 5 out of 14 patients showed strong lytic activity against NK-sensitive target cells. In this system, IFN-alpha failed to induce cytotoxic activity against NK resistant target cells in MNC from all the patients studied. This in vitro induction of cytotoxic activity in MNC from some patients with glioblastoma by IFN-alpha suggests a potential immunotherapeutic use of the lymphokine in these subjects. PMID- 1858529 TI - Muscle basal lamina as a grafting material for elongation of axons from rat brain. AB - Autografts of peripheral nerve or allografts of muscle basal lamina were inserted into the putamen-caudate complex of rats, with the outer end of the implant being sutured to the temporalis muscle. Elongation of central axons within the grafts, as revealed by the horseradish peroxidase retrograde labelling technique, did occur in the presence of basal lamina implants. With both types of grafting materials stained neurones exhibited a comparable distribution, being mainly found in the proximity of the central tip of the grafts. However, labelled cells in the presence of basal lamina were limited in number, compared with peripheral nerve autografts. Therefore, the usefulness of implants of muscle basal lamina into the central nervous system, in order to direct regenerating central axons toward distant target regions, is limited. This material might be suitable, as an alternative grafting material, in experimental models where avoidance of neurological impairment or size and length of the graft are crucial factors. PMID- 1858530 TI - Rat middle cerebral artery occlusion using an intraluminal thread technique. AB - A modification of the previous methods of producing cerebral ischaemia in rats (Koizumi et al., Longa et al.), using an intraluminal thread technique, is described. The middle cerebral artery is occluded by introducing a simple 3-0 nylon thread (0.20-0.249 mm in diameter) through the internal carotid artery in the neck. It has been proven that with this method reproducible focal cerebral ischaemia can be achieved which resembles human stroke. Therefore this simple and relatively non-invasive model is suitable for the pathophysiological investigation of ischaemic stroke and the testing of potential therapies. PMID- 1858531 TI - Acute effect of neodymium yttrium aluminium garment laser on the cerebral cortical structure, blood-brain barrier, and pial vessel behaviour in the cat. AB - Experimental brain lesions were created by Nd:YAG laser (wave length 1.06 microns) irradiation on the cerebral cortex of anaesthesized adult cats with 20 Watts impacts of 0.5, 1.0, 2.5, and 5.0 seconds exposure time through cranial windows. Histological changes, disruption of the blood-brain barrier (Evans blue extravasation) and pial vessel reaction (large vessels more than 100 microns and vessels smaller than 100 microns) were studied under constant PaCO2, blood pH, and mean arterial pressure. Histological changes of the lesions consisted of a zone of dense coagulation, a pale zone of homogeneous coagulation and an oedematous zone. Evans blue extravasation was uniformly seen extending from the histologically changed area into the surrounding tissue in all experiments. Pial arteries in the area with morphological changes showed pronounced dilatation (100.0 +/- 7.2%) and one third of these arteries were closed by thrombi. Pial arteries in the area of Evans blue extravasation but outside of histological changes also dilated (large arteries 60 +/- 4.1%, small arteries 77 +/- 5.9%). Pial arteries outside of the Evans blue extravasation were affected transiently and only in a very small zone: Within a distance of 200 microns from the Evans blue extravasation, large arteries initially dilated by 41 +/- 8.3%; small arteries dilated within 400 microns (42 +/- 3.7%). Within 4 minutes after irradiation arterial dilatation was again significantly reduced (p less than 0.01). It is concluded that no important vascular changes occur beyond the zones of histologically altered brain tissue. PMID- 1858532 TI - Meningioma presenting at a site of a previously aspirated brain abscess. AB - We report the case of a meningioma which developed in the parieto-occipital lobe at the site where a brain abscess had been aspirated 9 years previously. There was no history of head trauma. To the best of our knowledge this is the first reported case of a meningioma associated and possibly aetiologically related to a previous inflammatory process in the absence of head trauma. The association of chronic inflammation and the subsequent development of a meningioma is discussed. PMID- 1858533 TI - Fibrosarcoma of the scalp following postoperative radiotherapy for medulloblastoma. AB - A rare case of fibrosarcoma of the scalp following postoperative radiotherapy for medulloblastoma is reported. A review of similar cases in the literature was undertaken in an attempt to find a correlation between the dose of radiation, the length of the latent period, and the nature of the neoplasm. A significantly shorter latent period was found for sarcomas. No relationship was observed between the radiation dose and the latent period. The present case is unique in that the post-irradiation neoplasm (PIN) occurred in a predominantly extracranial site after treatment for a desmoplastic medullobastoma and had a remarkably short latent period. PMID- 1858534 TI - Atypical vertebral artery in a patient with an intra-and extraspinal cervical neurenteric cyst. AB - A 15 year old girl experienced Horner's syndrome on the right side, paraesthesia of the right arm and meningitis. CT and MRI showed a cystic lesion on the right side of the cervical spine at C3/C4 which descended with an extraspinal portion down to C6. Histology revealed a complex neurenteric cyst. The ipsilateral vertebral artery showed an atypical course. This abnormal artery besides a partial fusion of the vertebrae C2/C3/C4 suggest a complex malformation at the site of the cyst. Disturbed developmental relationships in this case indicate that pathological blood vessels may represent a risk factor in the surgical treatment of neurenteric cysts. PMID- 1858535 TI - Anterior-sacral meningocele; value of magnetic resonance imaging and abdominal sonography. A case report. AB - With the presentation of a case of giant anterior sacral meningocele, the evident superiority of magnetic resonance imaging over any other methods for the diagnosis of this rare condition is demonstrated. Ultrasound as a screening tool is often the first to reveal the presence of the intrabdominal cystic abnormality and furthermore is an excellent means for checking the post-operative course. In addition this particular case is interesting because the dural stalk linking the meningocele to the dural abdominal sac was not entirely free from nervous structures inspite of macroscopic appearances to the contrary. PMID- 1858536 TI - Meningitis after transsphenoidal pituitary adenoma removal, but without CSF fistula. PMID- 1858537 TI - Clipping of the anterior communicating artery to eliminate the contralateral blood supply in supratentorial large AVM of the carotid system. A report of 22 cases. AB - Large supratentorial arteriovenous malformations (AVMs) of the carotid system are vascularized by the ipsilateral internal carotid artery (ICA) and often, in addition, by the contralateral ICA via the anterior communicating artery (ACoA). In these AVMs we have previously advocated (1981) multiple staged operations with the progressive reduction of the blood stream passing through the AVM. In twenty two cases, starting in 1983, the reduction of the blood stream into the shunt has been performed as a first operation by placing a clip on the middle of the ACoA through a pterional approach on the opposite side of the AVM before radical open surgery. Results were excellent when considering the control angiogram and the measurement of the blood velocity in the ICA opposite to the AVM side. There were no neurological complications and no mortality. PMID- 1858540 TI - Transcriptional regulation of the human apolipoprotein genes. PMID- 1858538 TI - Thromboembolic phenomena in neurosurgical patients operated upon for primary and metastatic brain tumors. AB - A retrospective study was designed to evaluate clinical thromboembolic phenomena (TEP) in patients operated upon for brain tumours. Among 492 patients treated surgically in the supratentorial area, the overall incidence of clinical TEP was 7%. There were 5% with deep vein thrombosis (DVT) and 4% with clinical pulmonary embolism (PE). Seven patients (1%) died from massive PE. Among 141 patients treated surgically in the infratentorial area there were no episodes of TEP. Significant risk factors for TEP development were operations in the supratentorial area, malignant gliomas (compared to meningiomas) and para- or hemiparesis. Age, sex and the specific location in the supratentorial area were not found to be statistically significant risk factors. Among 12 patients who presented initially with DVT two developed PE despite full heparinization. 7/19 patients with PE died within minutes to hours of the clinical episode despite full conservative measures. In 2/26 patients who were treated with full heparinization complications occurred. There was one case of diffuse subcutaneous bleeding and one case of tumour bed haematoma. The identification of risk factors for the development of TEP will allow the implementation of prophylactic measures in appropriate patients undergoing elective brain tumour surgery. PMID- 1858539 TI - Highly sensitive detection of beta-2 transferrin in rhinorrhea and otorrhea as a marker for cerebrospinal fluid (C.S.F.) leakage. AB - As beta-2 transferrin is almost specific to the cerebrospinal fluid, its detection in rhinorrhea or otorrhea fluids demonstrates the occurrence of CSF fistula. We describe a highly sensitive method based on immunoaffinity-mediated capillary blotting for the detection of this cathodic isoform of transferrin in minute amounts (3 microliters) of rhinorrhea or otorrhea fluids. Application of this method in a series of 10 patients with CSF fistula is reported. PMID- 1858541 TI - Distribution of cholesterol within high density lipoproteins fractionated by immunoaffinity chromatography. PMID- 1858542 TI - Metabolic role of human apoprotein A-IV. PMID- 1858543 TI - Regression of atheroma and putative role of CETP in cholesteryl ester removal. PMID- 1858544 TI - Symmetry of the surface, and structure of the central core of human LDL particles, analyzed by X-ray small angle scattering. PMID- 1858545 TI - Alterations of high density lipoproteins induced by thyroid hormones in man and rat. PMID- 1858546 TI - The HELP-system in the treatment of severe hypercholesterolaemia: acute and long term experience. AB - The HELP procedure provides a new means of treating high LDL concentrations in severe hypercholesterolemia with the unique additional effect of lowering Lp(a) and fibrinogen. In combination with HMG-CoA-reductase inhibitors a mean interval value of -75% for LDL as compared to the starting concentration may be achieved. The treatment has the advantage that the patient is not exposed to foreign proteins or compounds with attendant immunological problems. It displays a high degree of reproducibility and an almost unlimited capacity guaranteeing a constant therapy independent of the clinic performing the treatment. The first coronary angiographies after 2 years of HELP treatment in over 50 patients (to be reported elsewhere) give support to the hope that regression of coronary heart disease is possible in humans. Further studies and observations should eventually tell us at what level of LDL, Lp(a) and fibrinogen this may be expected. We trust that the clinical benefit of this treatment regimen will be substantial for those patients who have problems in clearing LDL from their plasma pool and who are at the same time sensitive to elevated LDL-levels by the development of premature coronary sclerosis. PMID- 1858547 TI - Familial hypocholesterolemia and HDL deficiency. PMID- 1858548 TI - Mechanisms of hypocholesterolemia. PMID- 1858549 TI - Berman's simulation analysis and modeling. PMID- 1858550 TI - Considerations in designing and analyzing data from apo-B turnover studies. PMID- 1858551 TI - What is meant by overproduction of apo B-containing lipoproteins? PMID- 1858552 TI - Kinetics of heterogeneous populations of particles. PMID- 1858553 TI - Kinetic studies of the origin of apolipoprotein (apo) B-100 in low density lipoproteins of normal and Watanabe heritable hyperlipidemic (WHHL) rabbits. PMID- 1858554 TI - Mutations and variants of apolipoprotein B that affect plasma cholesterol levels. AB - Apolipoprotein (apo-) B100 is the exclusive apolipoprotein of low density lipoproteins (LDL0, which transport most of the plasma cholesterol in humans. Mutations in apo-B100 can cause either hypocholesterolemia or hypercholesterolemia. Familial hypobetalipoproteinemia, which leads to hypocholesterolemia, has been shown to be caused by defects in the apo-B gene that terminate translation prematurely and result in the production of truncated proteins. The mutations responsible for the hypocholesterolemia have been either single nucleotide substitutions or deletions. Familial defective apo-B100, which leads to hypercholesterolemia, is caused by a point mutation in the receptor binding domain of apo-B100. The mutation disrupts the binding of LDL to the LDL receptor, thereby disrupting LDL receptor-mediated catabolism and resulting in hypercholesterolemia. A variant form of apo-B, apo-B48, is also critical for lipoprotein metabolism. Apolipoprotein B48 is obligatory for the secretion of chylomicrons. It is formed from an RNA-edited apo-B mRNA in which codon 2153 has been converted from a CAA (glutamine) codon to a premature UAA (stop) codon. The first cytosine in this codon is deaminated to form uracil. The minimum nucleotide recognition sequence for the editing mechanism has been reported to be between 26 and more than 63 nucleotides surrounding codon 2153. The apo-B mRNA editing mechanism, which appears to be a cytosine deaminase, and its regulation are being actively investigated. PMID- 1858555 TI - Alterations in cholesterol metabolism in the genetically hypercholesterolemic RICO rat: an overview. PMID- 1858556 TI - Genetic variation at the lipoprotein lipase gene associates with coronary arteriosclerosis. PMID- 1858557 TI - The lipid surface of triglyceride-rich particles can modulate (apo)protein binding and tissue uptake. PMID- 1858558 TI - Structure and metabolism of low density lipoproteins from normal and hypertriglyceridemic subjects. PMID- 1858559 TI - The apoB 100-apo(a) complex: relation to triglyceride-rich particles. PMID- 1858560 TI - apoB-containing lipoprotein particles as risk factors for coronary artery disease. PMID- 1858562 TI - Concomitant inhibition of VLDL triglyceride and apoprotein secretion by hepatocytes of rats adapted to a high-fat diet. PMID- 1858561 TI - In vitro binding and in vivo uptake of chylomicron remnants after their hydrolysis by hepatic lipase. PMID- 1858563 TI - Molecular genetics of apoC-II and lipoprotein lipase deficiency. PMID- 1858564 TI - Molecular genetics of familial hypercholesterolemia. PMID- 1858565 TI - What factors regulate the action of lipoprotein lipase? PMID- 1858566 TI - Cytotoxicity of remnants of triglyceride-rich lipoproteins: an atherogenic insult? AB - None of more widely accepted theories of atherogenesis can explain all the more pertinent features of atherosclerosis: a) foam dell formation; b) endothelial cell stress/injury; c) protective effect of HDL; d) atherogenicity of triglyceride-rich lipoproteins; e) the vesicular nature of early lipid deposits in atherosclerosis, f) dissociation of diet risk from the risk due to elevation in plasma cholesterol; or g) correlation of postprandial lipemia with CAD risk. The data obtained from our studies provide a new theory of atherogenesis. This theory is that: a) lipolytic surface remnants of TG-rich lipoproteins may represent a major class of atherogenic lipoproteins which are exacerbated during postprandial hyperlipidemia; b) clearance of these surfaces remnants by HDL in vivo may be one important way that HDL prevents atherosclerosis; c) excess surface remnants may be linked to delayed clearance of potentially atherogenic core remnants, directly linked to atherogenicity via surface remnant-mediated cytotoxicity to cells of the artery wall and/or linked to the deposit of unesterified cholesterol-rich vesicles in early atherosclerosis. An appealing aspect of this hypothesis is that it can account for several unexplained features of atherosclerosis, such as anatomic differences in susceptibility to atherosclerosis in the vascular tree, the preference of early atherosclerosis in humans to the region of the coronary artery subjected to low hemodynamic shear stresses, and the vesicular nature of lipid deposits in early atherosclerosis. PMID- 1858567 TI - The role of oxidized LDL in atherosclerosis. PMID- 1858568 TI - Probucol and its mechanisms for reducing atherosclerosis. PMID- 1858569 TI - Proteoglycans, lipoproteins, and atherosclerosis. AB - The arterial wall proteoglycans play a crucial role in the pathogenesis of atherosclerosis as depicted schematically in Figure 7. Plasma components including lipoproteins cross the endothelium mainly by a non-specific bulk-phase vesicular transport. A selective interaction of apoB-containing lipoproteins occurs with proteoglycans of the subendothelial layer which results in extracellular retention and accumulation of lipoproteins. Such interaction alters the structural and charge characteristics of LDL particles. These altered LDL are taken up by monocyte-derived macrophages by scavenger receptor-mediated endocytosis, leading to cholesteryl ester accumulation and foam cell formation. Further, retention of LDL by proteoglycans in the extracellular matrix also increases the chances of oxidative modification of lipoproteins. All of these changes may be occurring at a marginal level as a normal adaptive process of the arterial wall. However, focal response to chronic hemodynamic stress, hyperlipidemia or other forms of injury may functionally alter the endothelium, and cause greater influx of lipoproteins and smooth muscle cell proliferation, resulting in increased synthesis of proteoglycans with altered characteristics. Enhanced binding of apo-B containing lipoproteins to proteoglycans under these conditions sets the stage for the development of athersclerosis. PMID- 1858570 TI - Immune mechanisms in the pathogenesis of atherosclerosis. PMID- 1858571 TI - Investigation of structural domains in human serum low density lipoprotein apolipoprotein B100. PMID- 1858572 TI - Cholesterol level in circulating immune complexes as a marker of coronary atherosclerosis. PMID- 1858573 TI - Antibody-like immunoglobulins G against low density lipoprotein that stimulate lipid accumulation in cultured cells. PMID- 1858574 TI - Nutritional regulation of apolipoprotein genes: effect of dietary carbohydrates and fatty acids. AB - The effect of nutritional factors on apolipoprotein gene expression by rat liver were studied. Dietary carbohydrates or fatty acids regulate the expression of apo E gene, by altering either gene transcription or mRNA stability. Conversely, apo AI regulation occurs at a post transcriptional level. In vivo and in vitro experiments gave contradictory results concerning apo B gene expression. The more dramatic changes in plasma lipids and apolipoproteins are obtained under dietary fish oil. Hepatocytes from fish oil-fed rats retain for several days modification in fatty acid metabolism, i.e. a shift in oleic acid channeling towards oxidation at the expense of esterification and a reduced ability to synthesize and secrete triacylglycerol. These modifications are paralleled with a decrease in the synthesis and in the secretion of apo Bs. Hepatocytes from fish oil fed rats secrete degradative forms of apo B which might result from either a sluggish VLDL synthesis and secretion or a more specific effect of n-3 long chain polyunsaturated fatty acid peroxidative products. Hepatocytes from fish oil fed rats exhibit a reduced ability to synthesize cholesterol, associated with a decrease in apo AI synthesis and secretion without any modification in apo AI mRNA. In contrast, the hepatocytes exhibit a concomitent decrease in apo E synthesis and secretion and in cellular apo E mRNA levels. PMID- 1858575 TI - Lipoprotein structure and metabolism during progression and regression of atherosclerosis in pigs fed with fish oil-derived fatty acids. PMID- 1858576 TI - Implications of thiolester linked fatty acids in apolipoprotein B. PMID- 1858577 TI - Factors regulating the distribution of cholesterol between LDL and HDL. PMID- 1858578 TI - Human plasma lecithin:cholesterol acyltransferase (LCAT). On the role of essential carboxyl groups in catalysis. PMID- 1858579 TI - Plasma lipoprotein phenotype in response to cholesteryl ester transfer protein levels in dyslipoproteinemia. PMID- 1858580 TI - [Immunosuppressive acidic protein (IAP) and immunosuppressive substance (ISS) in patients with renal cell carcinoma]. AB - To clarify their usefulness as markers for renal cell carcinoma, serum immunosuppressive acidic protein (IAP) and serum immunosuppressive substance (ISS) were evaluated by TIA (turbidometric immunoassay) for IAP and by SRID (single radial immunodiffusion) for ISS. The mean level of IAP and ISS was beyond each upper normal limit (500, 700 micrograms/ml) in every stage, and especially high in the M1 group. The levels of IAP and ISS were significantly correlated with each other. The determination of IAP and ISS levels after treatment showed a good correlation to the clinical course of the disease. The positive rates of IAP and ISS increased as the stages progressed, respectively. When the influences of pretreatment IAP and ISS level on survival period were investigated, the low IAP or ISS level group (less than two times of the upper normal limit) tended to have a better prognosis than the high level group (more than two times of the upper normal limit) in the M1 patients. These findings suggested that IAP and ISS could be used as markers for monitoring a disease and predicting the prognosis in patients with renal cell carcinoma. As for the positive rate in the combination assay for IAP, TPA and ferritin, or ISS, TPA and ferritin, more than 80% of the patients with low stage renal cell carcinoma had at least one positive marker. This suggested that the combination assay of these three markers was clinically valuable as a disease monitor in patients with renal cell carcinoma. PMID- 1858581 TI - [Statistical analysis of tumors of the renal pelvis and the ureter--determinants of prognostic significance]. AB - Sixty-two patients with epithelial tumors of the renal pelvis and the ureter were studied with respect to 16 clinicopathological factors and their relationship to the patients survival. The cumulative survival curves are depicted by the Kaplan Meier method and the statistical difference in the survival rates were detected in 11 factors, age, tumor number, multicentricity, tumor size, histological tumor type, stage, grade, growth pattern, infiltration pattern, lymphatic invasion and venous invasion. Cox's proportional hazard model was applied to evaluate the contribution of these 11 factors to survival. With the univariate analysis, lymphatic invasion showed the greatest hazard ratio followed by growth pattern, stage, venous invasion, age, and grade in this order. Stepwise selection of these factors based on the relative magnitude of their contribution to the survival with Cox's proportional hazard model revealed the most important factor for survival as the lymphatic invasion (hazard ratio 5.29), followed by growth pattern (hazard ratio 2.89). In conclusion, patients with tumor lymphatic invasion and tumor of non-papillary growth pattern showed poor prognosis, and adjuvant chemotherapy should be performed on them to improve their survival. PMID- 1858582 TI - [Non-invasive imaging diagnosis of left renal vein compression causing hematuria. Part 1. Ultrasonography]. AB - Left renal veins of 100 out-patients were examined by transabdominal ultrasonography to evaluate its usefulness in determining left renal vein compression which is causing renal bleeding. Ultrasonography revealed the left renal vein in 86 patients. In 61 of the 86 cases, the internal cavity of left renal vein was opened at least in diastolic phase, but in 23 cases, the internal cavity was closed between the abdominal aorta and the superior mesenteric artery in both systolic and diastolic phases. In the remaining 2 cases, left renal vein was compressed at a point where it intersected the right renal artery. Left renal vein compression was observed in 18 (69%) of the 26 cases which had been classified as idiopathic renal bleeding and in 7 (26%) of the 27 cases which had urinary tract diseases causing hematuria. In 33 cases which did not have hematuria, left renal vein compression was not observed. These results suggest that diagnosis of left renal vein compression causing renal bleeding is possible by transabdominal ultrasonography. PMID- 1858583 TI - [Non-invasive imaging diagnosis of left renal vein compression causing hematuria. Part 2. CT]. AB - Left renal veins of 77 patients were examined by computed tomography (CT) to evaluate its usefulness in determining the left renal vein compression which is causing renal bleeding. From CT image, left renal vein compression was observed in 6 (86%) of the 7 cases which had been classified as idiopathic renal bleeding, in 9 (21%) of the 42 cases which had urinary tract diseases causing hematuria, and in 3 (11%) of the 28 cases which did not have hematuria. In 15 of the 18 cases of left renal vein compression, left renal vein was compressed between the superior mesenteric artery and the abdominal aorta, showing so-called nutcracker phenomenon. In the remaining 3 cases, however, the superior mesenteric artery provided sharp delineation from the abdominal aorta. The superior mesenteric artery and the abdominal aorta made the mean angle of 35.5 degree in patients with normal left renal vein, the mean angle of 45.4 degrees in those with left renal vein compression without nutcracker phenomenon, and the mean angle of 11.9 degrees in those with nutcracker phenomenon. CT was superior to ultrasonography, in revealing left renal vein compression. PMID- 1858584 TI - [Urinary bladder disturbances in cervical spondylosis: improvement after surgical and conservative treatment]. AB - Cervical spondylosis accompanied by urinary bladder disturbances in 38 patients was treated orthopedically in an attempt to improve the associated urinary bladder disturbances. Urodynamic examinations revealed that severe urinary bladder symptoms associated with detrusor sphincter dyssynergia are resistant to surgical and conservative treatment. PMID- 1858585 TI - [Continent urinary diversion using the appendix as a catheterizable stoma]. AB - Two patients with bladder cancer underwent construction of continent urinary reservoir using the in situ appendix as a catheterizable stoma after total cystectomy. Urodynamic study revealed that the reservoir had a large capacity of 500-800 ml and low pressure without the involuntary pressure spikes was maintained. X-rays of the reservoir showed no reflux. The patients achieved complete day and night-time continence. PMID- 1858587 TI - [A case of renal artery aneurysm with calcification]. AB - We report a case of left renal artery aneurysm with ring-like calcification in a 57-year-old man. The selective renal arteriography showed a 30 x 28 mm saccular type aneurysm arising from the periphery of the bifurcation of posterior segment artery. There were no clinical symptoms, such as hypertension and loin pain, but we performed aneurysmectomy for fear of rupture. Histopathological findings showed atherosclerotic changes with marked calcification of wall lacking natural collagen fibers. Renal artery aneurysm with calcification seldom ruptures because of its generally hard wall. However, as cases of rupture through weakness of calcification have been reported, we recommend positive surgical treatment. PMID- 1858586 TI - [Adrenal ganglioneuroma]. AB - We report a case of adrenal ganglioneuroma. A 29-year-old man was referred to our clinic for further investigation of right abdominal mass incidentally discovered by ultrasonography. Endocrinological study was unremarkable. Abdominal computed tomography revealed well-defined, 6-cm-long oval mass with mottled calcification. Adrenal scintigraphy showed enlarged adrenal gland with low accumulation. T1 image of magnetic resonance depicted hypointensity tumor in comparison with liver. Extirpation of this tumor disclosed yellowish white, homogeneous mass, 101 g in weight and 7 by 7 by 3.5 cm in diameter. Pathological diagnosis was ganglioneuroma. All reported cases of adrenal ganglioneuroma exceeded 5 cm in diameter. This indicates malignancy in computed tomography. Therefore, we should be careful in diagnosing ganglioneuroma. PMID- 1858588 TI - [Blind ending bifid ureter with stone in the blind branch: report of a case]. AB - Blind ending bifid ureter is a rare anomaly in the urinary tract. This anomaly may result from failure of a premature branch of the ureteral bud to join with the metanephric blastema. A 21-year-old man was admitted with macroscopic hematuria and colic pain in the left flank region. Urinalysis demonstrated hematopyuria and excretory urography suggested bifid ending accessory ureter with a stone on the left side. Surgical exploration showed that the accessory ureter was bifurcated from the left ureter at about 5 mm from the bladder wall and ran parallel with the left ureter. Although dense adhesions to the surrounding tissue existed, the accessory ureter was resected at the site of the junction. It measured 3 cm in length and 1 cm in greatest diameter. The stone found at the tip of the accessory ureter was composed of calcium oxalate (24%) and calcium phosphate (76%). Histological examination revealed that the ureter had all layers of normal ureteral structure and no renal tissue was identified in the specimen resected. During a follow-up period of 22 months after the operation, he was free of urinary tract infection and abdominal pain. Of 77 cases with blind ending bifid ureter reported in the Japanese literature, a ureteral stone was found in the blind branch in only 5 cases. PMID- 1858589 TI - [Intermittent hydronephrosis caused by ureteral polyp in childhood: report of a case]. AB - We report a case of ureteral polyp causing intermittent hydronephrosis in a 12 year-old boy. He was often hospitalized with episodes of right flank pain and gross hematuria. An excretory urogram (IVP) revealed mild hydronephrosis, but it showed a markedly dilated right renal pelvis during the attack. An Anderson-Hynes type pyeloplasty was done. At operation we found four ureteral polyps, and performed partial ureterectomy including polyps. Pathological examination showed fibrous ureteral polyps. He has reported no symptoms for 3 months after the operation. PMID- 1858590 TI - [A case of malignant pheochromocytoma of the urinary bladder]. AB - A 31-year-old man was admitted to our hospital because of miction pain and gross hematuria in August, 1988. Cystoscopic examination revealed a solid mass in the bladder. The histological diagnosis was pheochromocytoma of urinary bladder by biopsy. He had a history of syncope on urination several times. Abnormal elevation of serum noradrenaline was observed in hormonal studies and abnormal accumulation was seen in the bladder by 131I-MIBG scintigraphy. Total cystectomy, lymphadenectomy and urinary diversion were performed in November, 1988. Pathological diagnosis was pheochromocytoma of the urinary bladder with metastasis to both iliac lymph nodes. PMID- 1858591 TI - [Complete remission of lung metastases of bladder tumor treated by small dosage of UFT: a case report]. AB - The patient was a 61-year-old woman with bladder cancer presenting in stage pT3a, N0, M0, T.C.C. (GIII) greater than S.C.C. Following total cystectomy and one course of cisplatin, adriamycin, cyclophosphamide (CAP) as adjuvant chemotherapy, she was started on futraful and uracil (UFT) at a dose of 4 capsules daily and placed on observation. Since she complained of olfactory anesthesia at 2 months of treatment, the dosage of UFT was reduced to 2 capsules daily and the drug was withdrawn after another 2 months of treatment. With the detection of lung metastases one month later UFT was resumed at a dose of 2 capsules daily. At 4 months of resumed treatment the foci of metastasis completely disappeared. She has since shown a complete remission by small dosage of UFT (2 capsules daily) for 12 months or more. PMID- 1858592 TI - [Urinary diversion using an appendix: a report of two cases]. AB - We report two cases of urinary diversion through an appendix. Case 1. An 81-year old man was hospitalized with oliguria. The patient had a past history of left nephro-ureterectomy for left ureteral tumor. Ultrasound showed right hydronephrosis due to recurrence in the bladder and right ureter. A total cystectomy and partial ureterectomy were carried out, and an appendix conduit was constructed because the ureter was not sufficiently long for ureterocutaneostomy. Case 2. A 68-year-old woman with diabetic neurogenic bladder, hypothyroidism, and chronic obstructive lung disease was hospitalized with the complaint of difficulty in self-catheterization. Continent vesicostomy was carried out according to the method of Mitrofanoff using the appendix. Both patients were tubeless and without postoperative complications before discharge. Appendix conduit and Mitrofanoff operation, which can be performed by a simple surgical procedure, are considered to be applicable to poor risk cases. PMID- 1858593 TI - [A case of pelvic lipomatosis]. AB - This is a report of the fifth case of pelvic lipomatosis in Japan. A 52-year-old man presented himself in our hospital with a complaint of left lower abdominal pain on August 28, 1988. At that time, physical examination was unremarkable with the exception of mild obesity. The excretory urogram and retrograde pyelogram revealed left hydroureteronephrosis with tapering of the left lower ureter. Urethrocystogram showed an elongated posterior urethra with anterior displacement and elevation of the bladder. Computed tomography revealed excess of diffuse fatty tissue in the pelvic space with bladder deformity and rectal compression. Pelvic arteriogram demonstrated no neovascularity. A diagnosis of pelvic lipomatosis was established. He lost 6 kg by diet therapy. Left lower abdominal pain disappeared, but excretory urogram after eight months showed no changes. PMID- 1858594 TI - [Intrascrotal leiomyoma: report of a case]. AB - A case of intrascrotal leiomyoma is reported. The patient was a 56-year-old male who complained of painless mass in the scrotum. He noticed the mass about 10 years ago and it had gradually enlarged. The mass was removed surgically. Pathohistological diagnosis of the specimen was leiomyoma. The literature revealed 13 cases of intrascrotal leiomyoma in Japan. PMID- 1858595 TI - [Ectopic parathyroid adenoma: a case report]. AB - A 69-year-old woman suffered from bilateral renal stones. Laboratory examinations showed primary hyperparathyroidism. Neck exploration including left hemithyroidectomy and partial thymectomy failed to reveal the abnormal parathyroid gland. Localization studies were done for an ectopic parathyroid adenoma. Repeated selective arteriography with digital subtraction technique revealed an ectopic parathyroid adenoma in the upper mediastinum. Computed tomography, ultrasonotomography and selective venous sampling also confirmed this finding. Subsequently, mediastinal exploration with partial sternotomy was performed and the ectopic parathyroid adenoma was removed. We discuss the preoperative localization studies for ectopic parathyroid adenoma. PMID- 1858596 TI - Questions in a code. PMID- 1858597 TI - Psychostimulants and Tennessee law. PMID- 1858598 TI - Wound repair. PMID- 1858599 TI - Paper spacer device for inhalers. PMID- 1858600 TI - Doses per container of flunisolide. PMID- 1858601 TI - Adjunctive corticosteroid therapy for pneumocystis pneumonia in patients with AIDS. PMID- 1858602 TI - Adjuvant therapy in early breast cancer. AB - Breast cancer is the most common malignancy in women. Screening mammography can detect cancer in its early stages, when it is potentially curable. Adjuvant chemotherapy is of major benefit in node-positive patients. It is also beneficial in certain node-negative patients with a high risk of breast cancer recurrence; these patients should be identified and offered adjuvant therapy or enrolled in a clinical trial. PMID- 1858603 TI - Sonography in the diagnosis of acute appendicitis. AB - Acute appendicitis can be a diagnostic dilemma. The classic triad of leukocytosis, pain at McBurney's point and a history compatible with appendicitis has a diagnostic accuracy rate of only 80 percent. Ultrasonography, combined with this triad, can improve the diagnostic accuracy, decreasing the negative laparotomy rate from 20 percent to less than 10 percent. PMID- 1858604 TI - Preventive therapy for malaria. AB - The incidence of malaria in travelers returning to the United States has been increasing. Persons visiting areas where malaria is endemic should use insect repellent, wear clothing that covers the arms and legs, and remain in screened areas between dusk and dawn. Chemoprophylaxis for travelers consists of weekly doses of chloroquine; a new drug, mefloquine, should be used in the increasing number of countries where chloroquine-resistant malaria is found. Travelers to these areas should carry three tablets of pyrimethamine-sulfadoxine, which should be taken for presumptive treatment of malaria at the onset of chills and fever. It is essential that chemoprophylaxis be continued for four to five weeks after departure from endemic areas. In travelers who develop symptoms of malaria after returning from an endemic area, it is imperative that treatment be started even if blood smears are negative. PMID- 1858605 TI - Disulfiram: a guide to clinical use in alcoholism treatment. AB - One option for helping chronic alcoholics remain sober is disulfiram therapy. Patients who take disulfiram develop a sensitivity to alcohol, resulting in unpleasant reactions to even small amounts of alcohol. When it is used as part of a comprehensive program for alcoholics who wish to remain sober, disulfiram can be an effective treatment aid. PMID- 1858606 TI - Periodontal disease and the family physician. AB - Periodontal disease can be divided into two categories: gingivitis (inflammation of the soft tissue) and periodontitis (destruction of the alveolar bone). Swelling, erythema, bleeding and gingival recession are common signs of gingivitis. However, most patients with gingivitis are asymptomatic. When patients complain of tooth pain and mobility, they already have severe periodontal disease. Dental loss secondary to periodontal disease may result in inadequate mastication, impaired phonetics and loss of self-esteem. Patients should be counseled that good oral hygiene and regular dental examinations can prevent periodontal disease. PMID- 1858607 TI - Ulnar tunnel syndrome. AB - The ulnar tunnel syndrome is a relatively uncommon condition resulting from compression of the ulnar nerve as it passes through the loge de Guyon, or ulnar tunnel, in the wrist. The syndrome may cause weakness and atrophy of the intrinsic hand muscles and loss of sensation in the ulnar nerve distribution of the hand. The most common cause of ulnar tunnel syndrome is chronic occupational trauma, either from pressure exerted over the hypothenar eminence by a tool or from the use of the heel of the hand as a hammer. Nonoccupational etiologies include congenital, inflammatory, neoplastic, vascular, metabolic, degenerative and traumatic disorders. Diagnosis often requires neurophysiologic evaluation, in addition to a careful history and physical examination. Conservative treatment aimed at protecting the ulnar tunnel from trauma frequently is effective. Occasionally, surgical decompression of the ulnar tunnel is required. PMID- 1858608 TI - Office dermatologic testing: the scabies preparation. AB - Patients with scabies may present with urticarial, eczematous or excoriated papules, eczematous patches or, occasionally, nodules. It is often difficult to differentiate scabies from eczema, folliculitis, drug eruption or lichen planus. The classically described burrows are often not seen. The scabies preparation, as described in this article, will aid in making the proper diagnosis. PMID- 1858609 TI - Prevention of sports-related eye injury. AB - Sports-related eye injury is an important cause of vision loss. Many eye injuries can be prevented through the supervision of play, the enforcement of game rules and the use of eye protective devices. State-of-the-art eye protective devices incorporate highly impact-resistant optical material, usually polycarbonate lenses, in a sturdy frame. Protective devices are available for use in racquet sports, baseball, basketball, football, ice hockey and other sports. PMID- 1858610 TI - Pneumocystis carinii: a deadly opportunist. AB - Pneumocystis carinii pneumonia is a life-threatening complication of diseases and therapies associated with immunosuppression. Approximately 80 percent of patients with acquired immunodeficiency syndrome will develop pneumocystis pneumonia. Diagnosis is important, because effective therapy is available. In most cases, diagnosis can be made by sputum analysis. Bronchoalveolar lavage will yield a diagnosis in 85 to 90 percent of patients with pneumocystis pneumonia, and is used when sputum induction and analysis is unproductive, unavailable or negative. Transbronchial biopsy and, rarely, open lung biopsy will yield the etiology of pneumonia in the remaining patients. Pentamidine or trimethoprim-sulfamethoxazole is the treatment of choice. Toxicity often occurs, including hypoglycemia, nephrotoxicity, neutropenia and rash. Corticosteroids are helpful in moderate to severe disease. Mortality for the first episode of P. carinii pneumonia averages 20 percent. Prophylaxis effectively prevents and reduces the incidence of future episodes. PMID- 1858611 TI - Laser treatment of benign cutaneous vascular lesions. AB - Benign cutaneous vascular lesions have been treated with a wide array of modalities. Lasers are a comparatively new form of treatment for cutaneous blood vessel abnormalities. Initially, results following laser treatment were disappointing, primarily because of widespread thermal injury to surrounding normal tissue. Recent developments in laser technology and the introduction of the tunable dye laser offer the ability to selectively target laser energy at specific chromophores such as oxyhemoglobin. The technique of selective photothermolysis provides successful treatment of benign vascular lesions with minimal damage to adjacent structures. PMID- 1858612 TI - Temper tantrums. AB - Temper tantrums are a normal response to anger and occur commonly in the child between one and four years of age. They arise from the child's thwarted efforts to exercise mastery and autonomy. Tantrums occur more frequently in the active, determined child who has abundant energy. Parenting practices that may encourage tantrums include inconsistency, unreasonable expectations, excessive strictness, overprotectiveness and overindulgence. Boredom, fatigue, hunger or illness may reduce the child's tolerance for frustration. Management consists of teaching the parents to understand the underlying meaning of tantrums and to modify parental behaviors that may perpetuate or accentuate the problem. Temper tantrums are best handled by ignoring the outburst, offering nurturance to the child after the tantrum has subsided and helping the child learn to express negative feelings in more acceptable ways. PMID- 1858613 TI - Noninvasive diagnosis of deep venous thrombosis. AB - Deep venous thrombosis of the lower extremity poses a diagnostic challenge. Clinical signs and symptoms are often misleading, and sensitive and specific tests are essential for diagnosis. The cost, patient discomfort and risk of morbidity associated with contrast venography have led to the development of noninvasive diagnostic techniques such as Doppler ultrasound, impedance plethysmography and duplex ultrasound scanning. If noninvasive tests unequivocally indicate deep venous thrombosis, treatment may be started without the need for contrast venography. PMID- 1858614 TI - Nonpharmacologic treatment of urinary incontinence. AB - Standard therapy for urinary incontinence often includes pharmaceutical agents that carry a risk of side effects or interactions with other drugs. As an alternative, several nonpharmacologic management approaches are available. Scheduled voiding regimens are effective for patients who have uninhibited detrusor contractions, even when cognitive impairment is present. In motivated patients, pelvic muscle exercise is effective for stress incontinence. These methods are safe and inexpensive, and studies indicate that they can be as effective as or more effective than pharmaceutical agents. Other nonpharmacologic approaches to management include biofeedback techniques and electrical stimulation therapy. PMID- 1858615 TI - National medical and nursing organizations call for overturn of 'gag rule'. PMID- 1858616 TI - AIDS update. PMID- 1858617 TI - Early angioplasty in patients with acute myocardial infarction complicated by hypotension. AB - Emergency percutaneous transluminal coronary angioplasty was performed in 62 patients with acute myocardial infarction complicated by hypotension. All patients were treated within 12 hours of the onset of chest pain. Angioplasty was completely successful (residual lesion less than or equal to 50%) in 48 patients, partially successful (patent vessel greater than 50% residual lesion) in four patients, and unsuccessful in 10 patients. Patients in whom angioplasty was successful had a hospital mortality rate of 19%; those in whom angioplasty was unsuccessful or only partially successful had hospital mortality rates of 60% and 50%, respectively, (p = 0.012). Patients with occlusion of the proximal left anterior descending vessel had the highest failure rate (42%) and the highest mortality rate (67%). Other univariate predictors of hospital mortality were older age and elevated end-diastolic pressure. Successful emergency angioplasty improves mortality in patients with acute infarction complicated by hypotension. PMID- 1858618 TI - Intraaortic balloon pumping as the postangioplasty strategy in acute myocardial infarction. AB - To assess the usefulness of intraaortic balloon pumping (IABP) in acute myocardial infarction (AMI), 114 patients with anterior AMI undergoing emergency percutaneous transluminal coronary angioplasty (PTCA) for total occlusion of the left anterior descending artery were studied. After successful PTCA 66 patients were treated with conventional therapy (group I), and 48 patients were treated with IABP for 25 +/- 8 hours (group II). The reocclusion rate was significantly lower in group II (2.4% vs 17.7% p less than 0.05). An increase in ejection fraction in group II compared with group I was marginally significant (4.5 +/- 12.2% vs 9.2 +/- 13.0%, p = 0.08). Vascular complications occurred in two patients, but there were no deaths from IABP. These results suggest that after successful PTCA for acute myocardial infarction, IABP prevents reocclusion and may add strength to reperfusion in the improvement of left ventricular function. PMID- 1858619 TI - Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction. AB - The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 +/- 0.5 (SD), which was significantly higher than the 0.7 +/- 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area. PMID- 1858620 TI - Percutaneous transluminal coronary angioplasty of the left coronary artery in patients with chronic occlusion of the right coronary artery: clinical and functional results. AB - The safety and therapeutic benefits of percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery, the left circumflex coronary artery or both were assessed in 61 patients with chronic (greater than 3 months) occlusion of the right coronary artery. Recanalization of the right coronary artery was not performed before dilatation of left coronary artery lesions. All lesions could be dilated without an acute ischemic event in the catheterization laboratory. However, three patients underwent coronary artery bypass surgery within the first 8 days after coronary angioplasty. There were no in-hospital deaths. Of the remaining 58 patients, 51 (88%) had repeat angiography at a mean of 5.2 +/- 2.5 months. Patients were divided into two groups according to the presence (n = 17) or absence (n = 34) of restenosis defined as greater than or equal to 50% diameter stenosis at the dilated site. Baseline characteristics were comparable. The mean value for angina functional class at follow-up was significantly better in the group without than in the group with restenosis (0.4 +/- 0.6 vs 2.1 +/- 1.1, respectively; p less than 0.001). Sixty five percent of the patients without restenosis were asymptomatic at follow-up. Seventy-five percent of the predicted maximal physical capacity was reached by 76% of the patients without restenosis compared with 33% in the group with restenosis (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858621 TI - Percutaneous transluminal angioplasty involving internal mammary artery grafts. AB - With the increasing use of the internal mammary artery as the conduit of choice in coronary bypass surgery, it is anticipated that an expanding patient population will have stenosis, usually at the site of internal mammary-to coronary artery anastomosis. In our series 31 patients underwent dilatation at either the site of anastomosis (24), the native coronary artery beyond the anastomosis (4), or both (3) with no mortality, myocardial infarction, or need for emergency coronary artery bypass surgery. Angiographic and clinical success was achieved in 28 patients (90%). There were two internal mammary artery dissections with both patients requiring elective coronary bypass surgery. Of the patients in whom dilatation was successful, 22 (79%) have been followed for longer than 6 months and 19 (86%) have had sustained functional improvement at a mean of 35 months after angioplasty. One patient is to undergo repeat coronary bypass surgery. No patient has had a myocardial infarction or died during follow up. Although percutaneous transluminal coronary angioplasty of the internal mammary artery has inherent difficulties because of the anatomic characteristics of the vessel, it can be performed with a high degree of primary success and a low incidence of complications and can provide long-term clinical improvement. PMID- 1858622 TI - Effect of the degree of effort on exercise echocardiography for the detection of restenosis after coronary artery angioplasty. AB - To determine whether the accuracy of exercise echocardiography is affected by the degree of effort during exercise, we examined 101 patients who had 6 months earlier undergone successful coronary artery angioplasty, with resting and immediate postexercise echocardiography and same-day coronary angiography. A positive exercise echocardiographic response was defined as the development of a new or worsening wall motion abnormality postexercise, compared with resting wall motion. Significant coronary disease (greater than 50% diameter stenosis) was present in 48 patients, 38 of whom had single-vessel disease and 10 of whom had two-vessel disease. Exercise echocardiography correctly identified 32 patients with significant disease (sensitivity 67%) and 44 patients without significant disease (specificity 83%). The effect of the degree of exercise effort on the sensitivity and specificity of the test was evaluated by three criteria; (1) the percentage of maximum predicted heart rate (MHR), (2) the duration of exercise (DUR), and (3) the double product (DP). To determine the influence of the degree of effort upon sensitivity and specificity, the effort criteria were compared between patients with true positive (TP) tests to those with false negative tests (FN), and in patients with true negative (TN) tests compared with those with false positive (FP) tests. No significant differences were detected in MHR, DUR, or DP between TP versus FN patients or between TN versus FP patients. These results indicate that for symptom-limited exercise echocardiography in postangioplasty patients, neither sensitivity nor specificity is significantly affected by the degree of effort during exercise. PMID- 1858623 TI - Smoking and the risk of first acute myocardial infarction. AB - When analyzing risk factors for first acute myocardial infarction in the Copenhagen City Heart Study, a large prospective population study of 20,000 men and women, smoking was found to influence risk significantly in a dose-dependent manner, the risk increasing 2% to 3% for each gram of tobacco smoked daily. Risk was particularly associated with inhalation, the risk for inhalers being almost twice that of noninhalers. No difference in risk could be demonstrated between various types of tobacco (pipe, cigar/cheroots, or plain and filtered cigarettes). The risk seemed associated with current smoking only, inasmuch as the duration of the smoking habit was not important. Ex-smokers had the same risk as those who had never smoked regardless of duration of smoking and time elapsed since quitting. Relative excess risk was significantly higher in female smokers than in male smokers, and daily alcohol intake appeared to have some protective effect on the risk of first acute myocardial infarction among heavy smokers. PMID- 1858624 TI - Absent left main coronary artery: angiographic findings in 83 patients with separate ostia of the left anterior descending and circumflex arteries at the left aortic sinus. AB - Among 20,332 adult patients who underwent consecutive cardiac catheterization and coronary arteriography, 83 (0.4%) were angiographically identified as having an absent left main coronary artery. The angiographic characteristics of this coronary anomaly include: (1) the presence of two well-separated coronary ostia at the left aortic sinus resulting in separate origin of the left anterior descending and circumflex arteries; (2) an increased incidence of left coronary dominance; (3) a higher (6%) than usual (0.5% to 1.5%) incidence of myocardial bridging; (4) lack of a high incidence of congenital heart anomalies; and (5) an incidence of atherosclerotic coronary artery disease similar to that of patients whose left main artery is intact. In 39% of the patients difficulties in selectively cannulating the separate ostium of the circumflex artery and adequately opacifying this vessel resulted in a need to change the diagnostic catheter size. Recognition of this coronary anomaly is needed to ensure accurate angiographic interpretation and is important for patients undergoing cardiac surgery to selectively perfuse these separate vessels during cardiopulmonary bypass. PMID- 1858625 TI - Comparative effect of heparin treatment with and without strenuous exercise on treadmill capacity in patients with stable effort angina. AB - It has recently been demonstrated that treadmill capacity and collateral circulation improve as a result of exercise with heparin pretreatment in patients with effort angina. In the present study, we assessed whether heparin alone is effective in increasing treadmill capacity in 14 patients with effort angina. Patients were randomly assigned to one of two treatment arms: (1) group A--20 treadmill exercise periods with standard Bruce protocol twice a day for 10 days with heparin (5000 IU intravenously) pretreatment (seven patients) or (2) group B -10 injections of heparin calcium (10,000 IU subcutaneously) once a day for 10 days (seven patients). In group A, total exercise time was increased from 6.9 +/- 1.2 (SD) to 9.9 +/- 1.9 minutes (p less than 0.0005), as was the maximal double product, from 21,700 +/- 3,500 to 27,000 +/- 4,800 mm Hg/min (p less than 0.05). The double product at the onset of angina was also increased by 34% (p less than 0.05), and the double product at which ST depression (0.1 mV) first appeared was 22% (p less than 0.05) greater after treatment. In contrast, in group B, all of the above-mentioned parameters of treadmill capacity remained unchanged. These data indicate that heparin does not serve as an angiogenic factor by itself, but that it potentiates the ischemia-derived angiogenic factor. PMID- 1858626 TI - Heart rate response during exercise testing and ambulatory ECG monitoring in patients with syndrome X. AB - The response of the heart rate during exercise testing and 24-hour ambulatory electrocardiographic (ECG) monitoring performed with patients not receiving antianginal treatment was assessed in 26 patients (9 men and 17 women; mean age 51 +/- 8 years) with syndrome X (angina pectoris with normal coronary arteries), in 27 patients with coronary artery disease (10 men and 17 women; mean age 55 +/- 9 years), and in 21 healthy subjects (8 men and 13 women; mean age 47 +/- 11 years). In patients with syndrome X the slope of the regression line of heart rate versus time (heart rate/time slope) during exercise testing was similar to that of patients with coronary artery disease (3.3 +/- 0.8 versus 3.1 +/- 1.2 beats/min), but significantly lower than that in healthy subjects (4.2 +/- 1.1 beats/min; p less than 0.003). In patients with syndrome X the intercept of the heart rate/time slope was significantly higher than that in coronary artery disease patients and healthy subjects (102 +/- 15, 86 +/- 18, and 90 +/- 16 beats/min, respectively; p less than 0.015). Resting preexercise heart rate was also significantly higher in syndrome X, compared with coronary artery disease patients and healthy subjects (91 +/- 16, 79 +/- 16, and 80 +/- 14 beats/min, respectively). During ambulatory ECG monitoring, mean diurnal heart rate (from 6 AM to 6 PM) was higher in patients with syndrome X (83 +/- 8 beats/min) than in patients with coronary artery disease (75 +/- 8 beats/min) and healthy subjects (74 +/- 11 beats/min) (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858627 TI - Electrophysiologic and anatomic characteristics of ventricular tachycardia induced at the right ventricular outflow tract but not at the apex. AB - The site of ventricular stimulation is an important variable in the initiation of ventricular tachycardia (VT) by programmed ventricular stimulation. Among 169 patients studied consecutively, 17 (10%) had ventricular tachycardia induced by programmed electrical stimulation from the right ventricular outflow tract but not from the apex. Fourteen of these 17 patients had had prior myocardial infarction (12 had inferior, and two had both inferior and anterior myocardial infarction), two had a dilated cardiomyopathy, and one had a localized cardiomyopathy. Fourteen patients had echocardiograms suitable for analysis. Of these, 12 had posterior/inferior ventricular wall motion abnormalities located at the base of the heart. The ventricular effective refractory periods from the right ventricular outflow tract and right ventricular apex were 237 +/- 4 and 244 +/- 5 msec, respectively (p less than 0.05, mean +/- SEM). Induced VT had a cycle length of 229 +/- 4 msec and had the morphology of right bundle branch block in 12 patients, of left bundle branch block in three patients, and had both morphologies in two patients. In 14 patients the axis was superior. VT was initiated with two extrastimuli in 15 patients and with burst right ventricular pacing in two patients. Similar pacing techniques with identical pacing intervals did not induce VT at the right ventricular apex in 14 of these 17 patients. Further, among the 15 patients whose VT was induced at the right ventricular outflow tract with two extrastimuli, neither burst pacing (n = 13) nor two extrastimuli introduced at faster paced rates (n = 12) induced VT at the right ventricular apex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858628 TI - Late potentials are unaltered by ventricular filling pressure reduction in heart failure. AB - Exacerbation of heart failure may increase susceptibility to arrhythmias. Therefore tests to assess the risk of arrhythmia, performed after hemodynamic improvement, may be of limited value. To determine whether hemodynamic improvement alters ventricular late potentials detected by signal-averaged ECG, we studied 27 consecutive patients with dilated heart failure (left ventricular ejection fraction 0.20 +/- 0.06, 15 with coronary artery disease) before and 3 +/ 2 days after tailored vasodilator and diuretic therapy reduced ventricular filling pressures. QRS duration, terminal QRS amplitude (root mean square [RMS]), and low-amplitude (less than 40 microV) signal (LAS) duration were determined by an automated algorithm from the vector magnitude of the QRS high-pass filtered at 25 Hz and at 40 Hz. Despite marked decreases in pulmonary capillary wedge (27 +/- 7 to 16 +/- 5 mm Hg, p less than 0.001) and right atrial (13 +/- 7 to 7 +/- 4 mm Hg, p less than 0.001) pressures and a 20% increase in cardiac output, there was not a significant change in QRS duration, RMS, or LAS. Before and after therapy late potentials, defined as abnormal QRS duration RMS, or LAS, were present in 14 (52%) patients with filtering at 25 Hz and in 22 (81%) patients with filtering at 40 Hz. The signal-averaged ECG after hemodynamic improvement predicted the results during exacerbation of heart failure in all patients. Thus in patients with advanced heart failure the signal-averaged ECG obtained after hemodynamic improvement reflects the findings during exacerbation of heart failure. PMID- 1858629 TI - Frequency of deep venous thrombosis in asymptomatic patients with coronary artery bypass grafts. AB - The frequency of deep vein thrombosis (DVT) in patients undergoing coronary artery bypass graft (CABG) surgery has not been established. Therefore to estimate the frequency of clinically silent DVT, we performed ultrasound examinations of the leg veins in 29 asymptomatic CABG patients before hospital discharge. We used high-resolution B-mode ultrasonography with color Doppler imaging. Fourteen (48.3%, 95% confidence interval 30.1 to 66.4%) had 20 documented leg vein thromboses, and all but one patient had DVT limited to the calf veins. Of the 20 thrombi 10 (50.0%) were present in the leg ipsilateral and 10 (50.0%) in the leg contralateral to the saphenous vein harvest site. None of the DVTs were suspected clinically. DVT was not associated with any local sign attributed to saphenous vein harvest such as pitting edema, incisional drainage, or local tenderness or with any putative risk factor for DVT such as cigarette use, distant history of malignancy, or varicose veins. Follow-up of these patients 5 to 11 months after CABG surgery showed no clinical evidence of DVT or pulmonary embolism. Our findings indicate that asymptomatic DVT of the calf occurs with surprisingly high frequency, 44.8% after CABG surgery. Future studies in patients undergoing CABG surgery should address the natural history of asymptomatic DVT, determine its clinical importance, and develop optimal strategies for prophylaxis and treatment. PMID- 1858631 TI - Transesophageal color Doppler echocardiography of the normal St. Jude Medical mitral valve prosthesis. AB - Transesophageal color flow Doppler findings are reported in 36 patients with a St. Jude Medical mechanical mitral valve prosthesis who had no auscultatory evidence for prosthetic valve dysfunction. Multiple jets consistent with mitral regurgitation originating from the central and lateral portion of the prosthesis were found in all patients. Maximum jet length ranged from 11 to 51 mm (mean 21 +/- 9 mm). Maximum jet area ranged from 0.2 to 4.1 cm3 (mean 1.2 +/- 0.9 cm2). The color M-mode Doppler interrogation showed two distinct components of the regurgitant jet: brief early systolic flow consistent with valve closure followed by holosystolic regurgitant flow consistent with transvalvular leakage. Four patients (11%) had a maximum regurgitant jet length exceeding 30 mm and absence of early systolic closure regurgitant flow by M-mode color imaging, suggesting clinically silent paravalvular leakage. Two pin-sized paravalvular suture line defects were confirmed in one patient at cardiac transplantation. We conclude that transesophageal echocardiography is a highly sensitive method for detection of mitral regurgitation in the St. Jude Medical mitral prosthesis. Clinically silent paravalvular leakage should be suspected if the maximum jet length exceeds 30 mm and color M-mode interrogation fails to demonstrate an early systolic closure regurgitant flow component. PMID- 1858630 TI - Left ventricular outflow obstruction resulting from insertion of mitral prostheses leaving the native leaflets intact: adverse clinical outcome in seven patients. AB - Left ventricular (LV) outflow obstruction may result from retaining the anterior mitral leaflet when a mitral prosthesis is inserted in the mitral anulus. We retrospectively reviewed the echocardiograms (two-dimensional Doppler and Doppler color flow imaging, or transesophageal with color flow imaging) obtained in seven patients with preoperative mitral regurgitation who had a prosthesis implanted with the native mitral leaflets left intact. Systolic anterior motion of the native anterior mitral leaflet, as seen in dynamic LV outflow tract obstruction, was observed in six of seven patients. LV fractional shortening preoperatively was less than or equal to 0.25 in all (mean 0.20 +/- 0.04) and did not significantly (p = ns) increase postoperatively (mean 0.27 +/- 0.12). Color flow imaging revealed disturbed systolic flow in the LV outflow tract in five patients, and all had systolic anterior motion of the native anterior mitral leaflet. Continuous wave Doppler detected significant systolic LV outflow tract jets in five patients averaging 4.1 +/- 0.9 m/sec. Mitral prosthetic function was normal (pressure half-time of 81 +/- 25 msec and mean gradient of 7 +/- 3 mm Hg +/- SD) in five patients. Clinical follow-up revealed that all had died, six of them within 2 months of their operation. Thus systolic anterior motion of the native anterior mitral leaflet occurs commonly after prosthetic mitral valve insertion with the native leaflets left intact. Continuous wave Doppler often demonstrates increased systolic LV outflow tract velocities consistent with dynamic LV outflow obstruction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858632 TI - Usefulness of transesophageal echocardiography in the diagnosis of conditions mimicking aortic dissection. AB - Between September 1987 and April 1989, forty patients suspected to have aortic dissection were evaluated by transesophageal echocardiography. Aortic dissection was identified in 18 patients. This study evaluated the ability of transesophageal echocardiography in the assessment of the 22 patients in whom aortic dissection was not found. A range of pathologic conditions was diagnosed in these patients. Five patients had ischemic heart disease when they were initially seen. Among the remaining 17 only one patient had a normal aorta. Aortic disease was present in the other 16 patients with aortic dilatation in 10. Atheromas were detected in seven patients with concomitant aortic dilatation in five of them. An extrinsic aortic mass was present in two patients. Transesophageal echocardiography correctly identified an anastomotic leak at the site of left coronary artery implantation in a patient with a recent Bentall procedure, and a large mobile clot within the proximal descending aorta in a patient with blunt chest trauma. These findings obviated the need for other tests in 15 patients and led to surgery in four with no ancillary tests performed in three of them. Thus transesophageal echocardiography has an important role in assessing patients with suspected dissection. Aortic disease is common even in patients in whom aortic dissection is excluded, and some of the conditions can be just as life-threatening as dissection. Transesophageal echocardiography not only reliably identifies dissection but can also detect luminal and extraluminal diseases not adequately visualized by other modalities. PMID- 1858633 TI - Relationship of echocardiographic, shunt flow, and angiographic size to the stretched diameter of the atrial septal defect. AB - Stretched diameter of the atrial septal defect (ASD), measured by balloon sizing, is generally used as a guide to the selection of the size of the device utilized for transcatheter closure of the ASD. Balloon sizing is a cumbersome procedure and sometimes requires the use of very large size balloon catheters. Several methods of assessment of ASD size, namely, echographic, pulmonary-to-systemic flow ratio (Qp:Qs), and angiographic measures, were undertaken in a group of 16 patients, aged 7 months to 45 years (median, 4.5 years), who were being evaluated for transcatheter closure of ASD; the results were compared with the stretched diameter. Although the echographic size of the ASD (9.9 +/- 4.1 mm, mean +/- SD) is similar (p greater than 0.1) to the angiographic size (7.9 +/- 2.5 mm), it is much smaller (p less than 0.01) than the stretched diameter (16.1 +/- 5.3 mm). When the relationship between various measures of ASD was examined, although the Qp:Qs ratio and angiographic size have a significant (p less than 0.05) correlation with the stretched diameter (r = 0.55 and 0.54, respectively), the echo diameter has the best correlation coefficient, r = 0.82, p less than 0.001. The stretched diameter can be estimated by the equation: 1.05 x echo + 5.49 mm. It is concluded that the echographic diameter is a useful adjunct in the estimation of the stretch ASD diameter, which in turn can be used in the selection of the size of the device for transcatheter occlusion of the ASD. PMID- 1858634 TI - The ventilatory threshold: method, protocol, and evaluator agreement. AB - To evaluate the effects of different methods of detection, exercise modes, protocols, and reviewers on oxygen uptake (VO2) at the ventilatory threshold (ATge), 17 men with heart disease (mean age 59 +/- 6 years) and six healthy men (mean age 60 +/- 11 years) underwent six exercise tests on different days. Each subject performed three treadmill tests (Bruce, Balke, and ramp) and three bicycle ergometer tests (50 W/stage, 25 W/stage, and ramp) in random order. The ventilatory threshold was determined for each of the six exercise tests by three independent, blinded reviewers by means of graphic plots of three commonly used methods of determination: (1) changes in the ventilatory equivalents for VO2 and VCO2, (2) changes in end-tidal oxygen and carbon dioxide pressures, and (3) the intersection of the slope of VCO2 and VO2 (V slope). The largest variability in the ATge was observed with changes in the exercise protocol. The greatest absolute (ml/min) and percentage differences in oxygen uptake at the ATge as a result of changes in protocol, method of determination, and observers were 336 (36%), 125 (12%), and 70 (7%), respectively. The overall intraclass correlation coefficient for VO2 at the ATge among the three reviewers was 0.60 and among the three protocols was 0.85 (p less than 0.01). The V slope method of detection had consistently good agreement among reviewers and was least affected by the protocol. The variance in the ATge (excluding intersubject and error variance) accounted for by differences in protocol, method, and reviewer was 82%, 14%, and 4%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858635 TI - Intractable heart failure despite angiotensin-converting enzyme inhibitors, digoxin, and diuretics: long-term effectiveness of add-on therapy with pimobendan. AB - In 25 patients whose chronic congestive heart failure (CHF) had recently worsened to New York Heart Association class IV, pimobendan (5 to 20 mg/day) was added to maximum conventional therapy consisting of digoxin, diuretics, angiotensin converting enzyme inhibitors, coumadin derivatives to prevent thromboembolic complications, and amiodarone to suppress serious ventricular rhythm disturbances. CHF was fatal in less than 1 month in five patients (two had shown some initial improvement). The other 20 had sustained improvement by at least one functional class, interrupted by episodes of CHF that usually responded to intravenous therapy. Median survival was 12 months (range 10 days to greater than 3 years); five patients died suddenly, 12 died of intractable CHF, and two died of other causes. Six patients were alive 3 years after the onset of treatment with pimobendan. Add-on therapy with pimobendan produced a sustained improvement in many patients with severe CHF that was no longer responding to a combination of digoxin, diuretics, and angiotensin-converting enzyme inhibitors. PMID- 1858636 TI - Effect of exogenous fructose-1,6-bisphosphate on glycolysis in the isolated perfused rat heart. AB - To test the mechanism of action of fructose-1,6-bisphosphate (F-1,6-P2), experiments were conducted on isolated perfused rat hearts to measure the glycolytic rate supported by exogenous glucose with simultaneous measurement of oxygen consumption and the release of lactate and pyruvate. Glycolysis was assayed in terms of the release of tritiated water from [5-3H] glucose, a measure of the rate through the aldolase step. It was found that 5 mmol/L F-1,6-P2 reduced the glycolytic rate parallel to the decrease in oxygen consumption. The results suggest that the cardioprotective action of F-1,6-P2 is related to a substrate effect and a decrease in adenosine triphosphate consumption as indicated by a decrease in oxygen consumption in accordance with the recent demonstration of Ca2+ binding by F-1,6-P2. PMID- 1858637 TI - Pathophysiology of isolated systolic hypertension in elderly patients: Doppler echocardiographic insights. AB - Systemic hemodynamics were evaluated with aortic pulsed wave Doppler echocardiography in 79 elderly subjects with isolated systolic hypertension participating in the Systolic Hypertension in the Elderly Program (SHEP) and were compared with the values in 39 normal age-matched subjects. Cardiac output was elevated (4.50 +/- 1.13 L/min versus 3.94 +/- 1.12 L/min, p less than 0.05) in patients with isolated systolic hypertension in comparison with values in normal elderly subjects. Systemic vascular resistance did not differ between both groups (2140 +/- 536 dyn.sec/cm-5 versus 2011 +/- 553 dyn.sec/cm-5, p = NS). The mean acceleration of blood during left ventricular ejection was similar in patients with isolated systolic hypertension in comparison with normals (12.6 +/- 5.6 m/sec2 versus 11.5 +/- 3.5 m/sec2, p = NS). Patients with isolated systolic hypertension had significantly decreased arterial compliance, as measured by the stroke volume-to-pulse pressure ratio (0.77 +/- 0.26 cm3/mm Hg versus 1.11 +/- 0.30 cm3/mm Hg, p less than 0.0001). The prevalence of aortic and mitral regurgitation as well as valvular and annular calcification did not differ between analyzed groups. Isolated systolic hypertension in elderly patients appears to be multifactorial, with reduced arterial compliance and increased cardiac output both playing a role. PMID- 1858639 TI - A critical review of the relationship between impaired fibrinolysis and myocardial infarction. AB - To explore the relationship between impaired fibrinolysis and myocardial infarction, we conducted a literature search and reviewed the published data. The results indicate that myocardial infarction has a significant influence on fibrinolytic activity and that impaired fibrinolysis is more frequent in patients who have had a myocardial infarction than in healthy control subjects. Prospective cohort studies indicate that tests for global fibrinolytic activity are not of prognostic value for first or recurrent myocardial infarction. However, high levels of plasminogen activator inhibitor and low levels of tissue plasminogen activator activity were associated with an increased risk of reinfarction in survivors of a first myocardial infarction. Whether this relationship between impaired fibrinolysis and reinfarction is causal or coincidental is unclear. There is evidence that impairment of fibrinolytic activity is more marked in patients with myocardial infarction who have minimal coronary atherosclerosis than in those who have marked atherosclerosis, suggesting that impaired fibrinolytic activity might be of pathogenetic importance in this small subgroup of patients. PMID- 1858638 TI - Cardiac manifestations of acquired immune deficiency syndrome: a 1991 update. AB - Cardiac involvement is being identified more often clinically and at autopsy in patients with AIDS. Recent estimates suggest that in the United States as many as 5000 patients per year may have cardiac complications resulting from HIV infection. Patients with AIDS may have pericardial, myocardial, and/or endocardial disease. Pericardial tamponade and/or constriction may be related to neoplasms, infections, or nonspecific effusions. Myocardial dysfunction may result from specific neoplastic infiltration or myocarditis. Particularly intriguing is the role of HIV-1 in the nonspecific myocarditis and dilated cardiomyopathy that occurs in patients with AIDS. As in other debilitating conditions patients with AIDS can have nonbacterial thrombotic endocarditis. Infective endocarditis may be a complication, especially in AIDS associated with intravenous drug abuse. Most patients with AIDS have no overt clinical evidence of cardiac disease. When cardiac dysfunction does develop, the signs and symptoms are often misinterpreted to be the result of noncardiac causes (pulmonary failure or infection) which can mimic heart failure. This review is intended to alert the reader to the cardiac manifestations of AIDS, which present a number of diagnostic and therapeutic challenges. PMID- 1858640 TI - Percutaneous coronary mid-infra-red laser angioplasty. AB - A pilot study was performed to determine the safety and efficacy of coronary pulsed mid-infra-red laser angioplasty. The laser was coupled with a novel 2.0 mm multifiber catheter consisting of 37 optical fibers of 150 microns each arranged concentrically around a 0.018-inch central lumen and a soft leading tapered distal tip to maintain coaxial alignment and position plaque in front of fibers. The laser was operated at 500 millijoules/pulse, 3.5 Hz, and 250 microseconds/pulse. Twenty-three patients with stenosis or occlusion of the left anterior descending or right coronary artery were selected for laser treatment. In three patients the catheter could not be positioned against the obstruction. In the 20 remaining patients laser angioplasty increased the diameter of the lumen from 0.3 +/- 0.3 mm to 1.4 +/- 0.3 mm and reduced the stenosis from 91 +/- 8% to 57 +/- 10%. In three patients "stand-alone" laser treatment was sufficient. In 17 patients balloon dilatation further reduced the stenosis to 20 +/- 18%. In two patients who had previously undergone unsuccessful balloon angioplasty with high inflation pressure, laser angioplasty allowed subsequent successful dilatation with low inflation pressure. There were no deaths, perforations, dissections, or arrhythmias. One patient had abrupt reclosure 24 hours after the procedure. Spasm occurred in four patients, and six patients had chest sensations during laser emission. Thus mid-infra-red pulsed coronary laser angioplasty is safe and effective for recanalization of stenosed and totally occluded arteries. The efficacy may be sufficient for "stand-alone" laser treatment. The technique may improve the efficacy of balloon angioplasty in cases of unsuccessful primary dilatation. PMID- 1858641 TI - Initial clinical experience with a 48 by 48 element biplane transesophageal probe. AB - Recent technologic advances in ultrasound have resulted in the capability of transesophageal echocardiographic imaging in both transverse and longitudinal planes. Previous biplane probes suffered from inferior images because of reduced scan elements. We evaluated the utility of a prototype 48 X 48 element biplane transesophageal probe in 23 consecutive patients. Examinations were well tolerated with no side effects. In comparison to the single transverse plane, imaging with the longitudinal plane gave superior information on prosthetic valve pathology, atrial septal abnormalities, and pathoanatomy of the ascending aorta and mitral valve. Complementary information was provided by the longitudinal plane in patients with endocarditis and vegetations and in mitral protheses. Images obtained with this 48 X 48 element biplane probe along with color and spectral Doppler information were not perceptibly inferior to those obtained by single-plane probes. In conclusion, biplane transesophageal echocardiography with a 48 X 48 element probe indicates a great potential for enhanced three dimensional understanding of cardiac pathology and diagnostic yield in specific pathologies. PMID- 1858642 TI - Transluminal angioplasty of a single coronary artery. PMID- 1858643 TI - Transesophageal color Doppler diagnosis of anomalous origin of left circumflex coronary artery. PMID- 1858645 TI - Flash pulmonary edema secondary to upper airway obstruction. PMID- 1858644 TI - Thrombocythemia and coronary artery disease. PMID- 1858646 TI - Apparent reversibility of cocaine-induced congestive cardiomyopathy. PMID- 1858647 TI - Increased serum interleukin-6 in cardiac myxoma. PMID- 1858648 TI - Detection of a left atrial myxoma by systematic transesophageal echocardiography in stroke. PMID- 1858649 TI - Isolated right superior vena cava into the left atrium detected by contrast echocardiography. PMID- 1858650 TI - Subaortic aneurysm in infective endocarditis. PMID- 1858651 TI - Four-year follow-up of a pseudoaneurysm of the mitral-aortic fibrosa. PMID- 1858652 TI - Diagnosis of arteriovenous fistula between common iliac artery and vein by color Doppler flow imaging. PMID- 1858653 TI - Aortic injury as a complication of central venous catheterization. PMID- 1858654 TI - In utero echocardiographic diagnosis of premature closure of the foramen ovale with mitral regurgitation and large left atrium. PMID- 1858656 TI - Identifying patients for prophylactic automatic implantable cardioverter defibrillator therapy: status of prospective studies. PMID- 1858655 TI - Lipid transfer proteins, hypertriglyceridemia, and reduced high-density lipoprotein cholesterol. PMID- 1858658 TI - Chronotherapeutics can improve patient care. PMID- 1858657 TI - 'New order' for pharmacy explored. PMID- 1858659 TI - Pharmacy technicians: current status in the states. AB - This report indicates that considerable regulation of pharmacy technicians has been accomplished. It further points out that regulations differ among the states. Given the extent of activity to date and activity currently underway, the states are exerting influence on the future role of the pharmacy technician. PMID- 1858660 TI - Photoplex. PMID- 1858661 TI - An overview of adverse drug reactions. PMID- 1858663 TI - Selection of respiratory protection against carcinogens. PMID- 1858662 TI - AIHA position statement on the removal of asbestos-containing materials (ACM) from buildings. AB - The health risks associated with asbestos exposure for building occupants has been demonstrated to be very low. The decision to remove asbestos-containing materials (ACM) in undamaged, intact condition that are not readily accessible to occupants should be made only after assessing all other options. Both technical and financial issues should be fully explored by a team of trained specialists, including industrial hygienists, architects, and engineers. The optimal solution will vary from building to building, based on factors unique to each situation. One important consideration is the use of a well-designed air-monitoring program to identify changes in airborne levels of asbestos. Special training and maintenance programs are needed to ensure the safety and health of building and contract workers who may encounter asbestos or who may disturb it during routine or nonroutine activities. Each building owner who has ACM in a building should identify an in-house asbestos manager, and it is also necessary to provide appropriate resources, including professional consultants, to develop and manage a responsible and effective in-place management program throughout the life of a building containing asbestos. PMID- 1858664 TI - The physiological cost of wearing a disposable respirator. AB - In order to gain an understanding of the physiological stresses imposed by the wearing of a single-use disposable respirator, a series of experiments was done to measure the cardiopulmonary effects of wearing the respirator (heart rate, respiratory rate, and blood pressure); resistance to breathing while wearing a respirator; and heat stress imposed by the use of a respirator (changes in inspired and expired air temperature). Ten men, ages 24 to 35, of varying fitness levels, served as volunteers in the studies. All the men exercised on a treadmill both with and without 3M Model 8715 disposable respirators. Workloads corresponding to light, moderate, and heavy levels were calculated for each volunteer based on his maximal oxygen uptake. As work intensity increased, an increase in breathing resistance was found. Peak resistances were in the range of +/- 2 cm water. Work-intensity level increases in respiratory rates were found with and without the respirators, but the respirator use trial had a significantly increased respiratory rate. Heart rate also showed a dose-related increase as work intensity increased and was significantly greater in the respirator trials at heavy levels of work and during recovery. Systolic blood pressure showed a biphasic response to respirator use, being significantly lower at rest and higher at high levels of work. Diastolic blood pressure changes were less dramatic but were elevated in the respirator trials. Clinically important increases in blood pressure were found in two volunteers when respirators were worn. Air temperatures immediately anterior to the face were, on average, 7.5 degrees C higher in the respirator trials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858665 TI - A quantitative approach to the characterization of cumulative and average solvent exposure in paint manufacturing plants. AB - Previous reports have attributed a range of neurobehavioral effects to low-level, occupational solvent exposure. These studies have generally been limited in their exposure assessments and have specifically lacked good estimates of exposure intensity. In the present study, the authors describe the development of two exposure variables that quantitatively integrate industrial hygiene sampling data with estimates of exposure duration--a cumulative exposure (CE) estimate and a lifetime weighted average exposure (LWAE) estimate. Detailed occupational histories were obtained from 187 workers at two paint manufacturing plants. Historic industrial hygiene sampling data for total hydrocarbons (a composite variable of the major neurotoxic solvents present) were grouped according to 20 uniform, temporally stable exposure zones, which had been defined during plant walk-through surveys. Sampling at the time of the study was used to characterize the few zones for which historic data were limited or unavailable. For each participant, the geometric mean total hydrocarbon level for each exposure zone worked in was multiplied by the duration of employment in that zone; the resulting products were summed over the working lifetime to create the CE variable. The CE variable was divided by the total duration of employment in solvent-exposed jobs to create the LWAE variable. The explanatory value of each participant's LWAE estimate in the regression of simple visual reaction time (a neurobehavioral test previously shown to be affected by chronic solvent exposure) on exposure was compared with that of several other exposure variables, including exposure duration and an exposure variable based on an ordinal ranking of the exposure zones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858666 TI - The influence of the helmet respirator on peak flow rate in aluminum potroom. AB - The efficiency of the Racal Airstream helmet respirator in improving peak expiratory flow rates (PEFR) and symptoms (dyspnea, wheezing, and cough) in aluminum potroom workers with respiratory complaints was assessed in 19 workers. Peak expiratory flow readings and symptom recording from a 2-week working period with use of the respirator were compared with a period when the 3M 9906 disposable mask was used. The study was designed as a randomized, parallel, cross over study with five or six daily measurements of PEFR and daily symptom recording. A significant number of workers (15) had a higher mean peak flow in the helmet period than in the nonhelmet period (p less than 0.01); symptoms did not improve significantly in the helmet period. Objective evidence of respiratory protection was observed for the group of workers as a whole, but the effect on symptoms as well as individual effect on peak flow was minor in the majority of the workers. PMID- 1858667 TI - A comparison of controlled negative pressure and aerosol quantitative respirator fit test systems by using fixed leaks. AB - An automated version of a new method for quantitative respirator fit testing by controlled negative pressure was compared with a computerized aerosol fit test system. The controlled negative pressure technique eliminates many of the problems associated with aerosol and pressure decay fit test methods. A series of fixed leaks was used to compare the leak measurement capabilities of the controlled negative pressure system against a standard computerized aerosol fit test system. Negative pressure and aerosol fit factors determined for a series of fixed leaks through hypodermic needles were highly correlated with each other (r = 0.998) and with the cross-sectional areas of the leak needles (r greater than 0.995). PMID- 1858668 TI - Validated methods for degrading hazardous chemicals: some halogenated compounds. AB - Two techniques were investigated for degrading a number of halogenated compounds of commercial and research importance. Reductive dehalogenation with nickel aluminum alloy in potassium hydroxide solution was used to degrade iodomethane, chloroacetic acid, trichloroacetic acid, 2-chloroethanol, 2-bromoethanol, 2 chloroethylamine, 2-bromoethylamine, 1-bromobutane, 1-iodobutane, 2-bromobutane, 2-iodobutane, 2-bromo-2-methylpropane, 2-iodo-2-methylpropane, 3-chloropyridine, fluorobenzene, chlorobenzene, bromobenzene, iodobenzene, 4-fluoroaniline, 2 chloroaniline, 3-chloroaniline, 4-chloroaniline, 4-fluoronitrobenzene, 2 chloronitrobenzene, 3-chloronitrobenzene, 4-chloronitrobenzene, benzyl chloride, benzyl bromide, alpha,alpha-dichlorotoluene, and 3-aminobenzotrifluoride. The products were generally those obtained by replacing the halogen with hydrogen although concomitant reduction of the other groups was also observed. Bibenzyl was produced during the reduction of benzyl chloride, benzyl bromide, and alpha,alpha-dichlorotoluene. Refluxing with ethanolic potassium hydroxide was used to degrade iodomethane, chloroacetic acid, 2-fluoroethanol, 2-chloroethanol, 2-bromoethanol, 1-chlorobutane, 1-bromobutane, 1-iodobutane, 2-bromobutane, 2 iodobutane, 2-bromo-2-methylpropane, 2-iodo-2-methylpropane, benzyl chloride, benzyl bromide, 1-bromononane, 1-chlorodecane, and 1-bromodecane. The products were the corresponding ethyl ethers. 2-Methylaziridine was cleaved with nickel aluminum alloy in potassium hydroxide solution to a mixture of isopropylamine and n-propylamine. In all cases, the compounds were completely degraded and only nonmutagenic reaction mixtures were produced. PMID- 1858669 TI - Antiischemic and metabolic effects of glutamate during pacing in patients with stable angina pectoris secondary to either coronary artery disease or syndrome X. AB - The effects of glutamate on anginal threshold, cardiac metabolism and hemodynamics were studied in 11 patients with stable angina pectoris, positive stress test results, and pacing-induced myocardial lactate release due to coronary artery disease (CAD) (n = 9) or syndrome X (n = 2). Data were obtained before, during and after 2 identical periods of coronary sinus pacing, the second being preceded by an intravenous injection of monosodium glutamate 1.2 (n = 7) or 2.5 (n = 4) mg/kg body weight. After glutamate administration, pacing time to onset of angina increased from mean +/- standard deviation 103 +/- 53 to 166 +/- 71 seconds (p less than 0.01) and ST-segment depression after pacing decreased from 2.3 +/- 1.0 to 1.6 +/- 1.1 mm (p less than 0.01). Arterial glutamate concentration increased 60% (p less than 0.01) after the low dose and 150% (p less than 0.01) after the high dose of glutamate. Regardless of dose, myocardial glutamate uptake increased by 25% (p less than 0.01). Pacing-induced cardiac release of lactate diminished 50% (p less than 0.05), whereas the releases of xanthine and hypoxanthine were unchanged by glutamate. Arterial free fatty acids decreased 20% (p less than 0.01). Circulating levels and cardiac exchanges of alanine, glucose and citrate were unchanged. Glutamate did not influence heart rate, arterial blood pressure, coronary blood flow, coronary vascular resistance or myocardial oxygen consumption. One patient complained of short-lasting burning sensations after receiving the high glutamate dose. In conclusion, augmented provision of glutamate enhances pacing tolerance in stable angina, presumably by a metabolic improvement of cardiac energy production during ischemia. PMID- 1858670 TI - Angiographically assessed coronary arterial patency and reocclusion in patients with acute myocardial infarction treated with anistreplase: results of the anistreplase reocclusion multicenter study (ARMS). AB - In this open multicenter study, 156 patients with acute myocardial infarction received 30 U of anistreplase intravenously over 5 minutes within 4 hours of the onset of chest pain. The patency of the infarct-related vessel was determined by coronary angiography 90 minutes after anistreplase treatment, and also 24 hours after treatment, in patients with a patent infarct-related vessel at 90 minutes, to assess the reocclusion rate. The investigators categorized the infarct-related vessel as patent or occluded, and 2 independent cardiologists graded the infarct related vessel according to the Thrombolysis in Myocardial Infarction (TIMI) perfusion criteria. At the 90-minute assessment, 106 of 145 evaluable patients (73%) had patent infarct-related vessels, and 39 of 145 (27%) had occluded infarct-related vessels. Of the 139 independently assessed patients, 98 (71%) had TIMI grades 2 or 3 and 41 (29%) had TIMI grades 0 or 1. At the 24-hour assessment, 98 of 102 patients (96%) had a patent infarct-related vessel, and reocclusion had occurred in 4 of 102 patients (4%). Of the 94 independently assessed patients 90 (96%) had TIMI grades 2 or 3, and 4 (4%) had TIMI grades 0 or 1. The reliability of noninvasive parameters as indicators of achieved patency of the infarct-related vessel was estimated by means of correlation with patency assessed by coronary angiography. A significant correlation of 0.62 was found. The patency rate of 71 to 73% after use of anistreplase in patients with acute myocardial infarction corresponds with findings in earlier studies. The low reocclusion rate of 4% after use of anistreplase probably reflects the prolonged action of anistreplase. PMID- 1858671 TI - Acute effects of intravenous nicardipine on hemodynamics and cardiac function in patients with a healed myocardial infarction and no evidence of congestive heart failure. AB - Acute effects of intravenous nicardipine (10 micrograms/kg) on systemic hemodynamics and cardiac function were evaluated in 17 patients with a healed myocardial infarction and no evidence of congestive heart failure. Mean New York Heart Association functional class was 1.6 +/- 0.5 (mean +/- standard deviation). Aortic systolic pressure (p less than 0.001) and left ventricular end-diastolic pressure decreased (10 +/- 3 to 8 +/- 3 mm Hg, p less than 0.01), and systemic vascular resistance decreased significantly (p less than 0.001), whereas pulmonary and right atrial pressure and pulmonary arteriolar resistance did not change. Cardiac and stroke indexes showed biphasic changes. Although positive and negative maximal rate of left ventricular pressures decreased significantly (p less than 0.05 and p less than 0.01, respectively), they did not change significantly when aortic systolic pressure was corrected. There was a significant inverse correlation between the negative rate of left ventricular pressure/aortic systolic pressure before nicardipine infusion and its maximal percent increase after infusion (r = -0.56, p less than 0.05), indicating a beneficial effect on diastolic relaxation in patients with impaired diastolic function. Our data show that a low dose (10 micrograms/kg) of intravenous nicardipine exerts a favorable effect on impaired diastolic function, but depresses left ventricular pump function with much less effect on right heart circulation. PMID- 1858672 TI - Comparative efficacy and safety of bepridil and diltiazem in chronic stable angina pectoris refractory to diltiazem. The Bepridil Collaborative Study Group. AB - The efficacy and safety of bepridil hydrochloride (200 to 400 mg/day) were evaluated in patients with chronic stable angina refractory to maximal tolerated doses of diltiazem (median 360 mg/day) in a randomized, multicenter, double blind, parallel study. Baseline diltiazem data were obtained during a 2-week period, after which 86 patients were randomized to bepridil (n = 46) or diltiazem (n = 40). Angina frequency, nitroglycerin consumption and ischemic manifestations induced by exercise treadmill testing were evaluated over 8 weeks. Bepridil significantly (p less than 0.05) increased time to angina onset, time to 1 and 2 mm of ST-segment depression, total exercise time and total work over baseline values. Changes in time to angina onset and time to 1 mm of ST-segment depression were significantly (p less than 0.05) greater for bepridil than for diltiazem. Angina frequency and nitroglycerin consumption did not differ significantly between groups. Compared with baseline, bepridil significantly (p less than 0.001) decreased heart rate (mean 4 beats/min) and prolonged QTc (mean 35 ms). The most frequent adverse effects in both groups were nausea, asthenia, dizziness, headache and diarrhea. Four patients taking bepridil and 1 taking diltiazem withdrew from the study because of adverse reactions. No sudden deaths, myocardial infarctions or instances of sustained ventricular tachycardia or torsades de pointes occurred in either group. The data indicate that bepridil provided safe and effective antianginal and antiischemic therapy in patients with chronic stable angina who exhibited less than optimal response to maximal tolerated doses of diltiazem. PMID- 1858673 TI - Safety and efficacy of percutaneous transluminal coronary angioplasty in patients with left ventricular dysfunction. AB - The risks and long-term outcome after 845 elective percutaneous transluminal coronary angioplasties (PTCA) in patients with left ventricular (LV) dysfunction (ejection fraction less than or equal to 40%) were examined. Procedural results were compared with 8,117 consecutive procedures in patients with ejection fractions greater than 40%. The patients with LV dysfunction were older (63 vs 60 years, p less than 0.01), had a greater incidence of prior myocardial infarction (84 vs 45%, p less than 0.001), prior bypass surgery (39 vs 21%, p less than 0.001), 3-vessel disease (62 vs 33%, p less than 0.001), and class IV angina (48 vs 41%, p less than 0.01) than the control group. Angiographic success was lower (93 vs 95%, p less than 0.01), and overall procedural mortality was increased ( 4 vs 1%, p less than 0.001) in the study group. Emergency surgery rates were identical (2%). No significant difference was found in rates of nonfatal Q-wave myocardial infarction (2 vs 1%). At mean follow-up of 33.5 months, 15% of the patients with LV dysfunction required late bypass surgery, 27% underwent repeat PTCA, and 59% were angina free. Actuarial survival at 1 and 4 years was 87 and 69%, respectively. Cox regression analysis identified 3-vessel disease, age greater than or equal to 70 years, class IV angina and incomplete revascularization as correlates of long-term mortality. These data suggest that PTCA may be an effective treatment for coronary artery disease in patients with LV dysfunction. PMID- 1858674 TI - Comparison of exercise radionuclide angiography with thallium SPECT imaging for detection of significant narrowing of the left circumflex coronary artery. AB - Although quantitation of exercise thallium tomograms has enhanced the noninvasive diagnosis and localization of coronary artery disease, the detection of stenosis of the left circumflex coronary artery remains suboptimal. Because posterolateral regional wall motion during exercise is well assessed by radionuclide angiography, this study determined whether regional dysfunction of the posterolateral wall during exercise radionuclide angiography is more sensitive in identifying left circumflex disease than thallium perfusion abnormalities assessed by single-photon emission computed tomography (SPECT). One hundred ten consecutive patients with CAD were studied, of whom 70 had a significant stenosis of the left circumflex coronary artery or a major obtuse marginal branch. Both regional function and segmental thallium activity of the posterolateral wall were assessed using visual and quantitative analysis. Left ventricular regional function was assessed objectively by dividing the left ventricular region of interest into 20 sectors; the 8 sectors corresponding to the posterolateral free wall were used to assess function in the left circumflex artery distribution. Similarly, using circumferential profile analysis of short-axis thallium tomograms, left ventricular myocardial activity was subdivided into 64 sectors; the 16 sectors corresponding to the posterolateral region were used to assess thallium perfusion abnormalities in the left circumflex artery territory. Qualitative posterolateral wall motion analysis detected 76% of patients with left circumflex coronary artery stenosis, with a specificity of 83%, compared with only 44% by qualitative thallium tomography (p less than 0.001) and a specificity of 92%. Whereas quantitation of thallium activity increased the sensitivity for detecting left circumflex coronary artery stenosis to 80% with a specificity of 55%, it did not achieve statistical significance when compared with qualitative wall motion analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858676 TI - Left ventricular shape as a determinant of functional mitral regurgitation in patients with severe heart failure secondary to either coronary artery disease or idiopathic dilated cardiomyopathy. AB - The relation between left ventricular (LV) shape and functional mitral regurgitation (MR) was evaluated in 39 patients with congestive heart failure. Heart failure was due to coronary artery disease in 23 patients (group I) and to idiopathic dilated cardiomyopathy in 16 (group II). LV shape was quantitated based on the ratio of LV major-to-minor axis and LV sphericity index calculated at end-systole and end-diastole. In group I, 9 patients had angiographic evidence of MR and 14 did not. In group II, 10 patients had MR and 6 did not. Within each group, there were no differences between patients with and without MR with regard to LV chamber volume and regional segmental wall motion abnormalities. In both groups, however, a significant difference was observed between patients with and without MR with respect to end-systolic and end-diastolic LV shape indexes. In group I, the end-systolic major-to-minor axis ratio was lower in patients with (1.42 +/- 0.04) than without (1.72 +/- 0.05) MR (p less than 0.001). Similar differences were observed in group II (1.41 +/- 0.06 vs 1.69 +/- 0.04) (p less than 0.01). In group I, the end-systolic sphericity index was also greater in patients with (0.32 +/- 0.02) than without (0.25 +/- 0.01) MR (p less than 0.02). Similar differences were observed in group II (0.37 +/- 0.03 vs 0.26 +/- 0.01) (p less than 0.02). These data indicate that in patients with severe heart failure, functional MR is present in those who manifest a more spherical LV cavity. PMID- 1858675 TI - Stunned left ventricular myocardium after exercise treadmill testing in coronary artery disease. AB - Myocardial stunning (postischemic ventricular dysfunction) occurs in dogs after coronary stenosis following treadmill exercise. Less data are available in humans regarding development of stunned myocardium after exercise. Regional wall motion changes were evaluated in 22 patients with known coronary artery disease using 2 dimensional echocardiography and exercise treadmill testing. Wall motion was scored as 1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic. At least 1 left ventricular segment with normal resting function developed an increase in wall motion score at 15 or 30 minutes compared with values at rest. The wall motion score in the midportion of the ventricular septum increased from 1.0 at rest to 1.6 (p less than 0.004) at 30 minutes after exercise; the basal inferior wall score worsened from 1.0 at rest to 1.9 (p less than 0.01) at 30 minutes after exercise. Coronary angiographic data in these patients revealed that left anterior descending narrowing correlated best with left ventricular septal wall motion abnormalities, whereas right coronary artery and circumflex narrowing best correlated with inferior and posterior wall motion abnormalities. Eight normal adult volunteers with no history of myocardial ischemia also underwent 2 dimensional echocardiography and exercise testing. No wall motion abnormalities were observed at any time after exercise. The present study suggests that in patients with coronary artery disease, exercise treadmill testing may induce regional wall motion abnormalities of the left ventricle that persist greater than or equal to 30 minutes after exercise, an observation consistent with the phenomenon of stunned myocardium. PMID- 1858677 TI - Outcome of infants and children with dilated cardiomyopathy. AB - A review of 81 infants and children with dilated, poorly contracting left ventricles without associated structural abnormalities was undertaken to identify risk factors for poor outcome, which could be used in selecting candidates for cardiac transplantation. Significant atrial or ventricular dysrhythmias, or both, were detected on presentation or during follow-up in 24 patients. Arrhythmias were present in only 8 of 51 survivors (16%) but were detected in 16 of 30 patients (53%) who died (p less than 0.05). Patients dying suddenly were even more likely to have had documented dysrhythmias (8 of 11, p less than 0.05). Left ventricular shortening fraction was similar in survivors and nonsurvivors (14.9 +/- 1.0% vs 15.3 +/- 1.7%). Left ventricular end-diastolic pressure in 44 patients who had cardiac catheterization averaged 20.8 +/- 1.6 mm Hg. Left ventricular end-diastolic pressure was significantly higher in patients who died than in those who survived (29.5 +/- 2.2 vs 15.0 +/- 1.6 mm Hg, p less than 0.001). Analysis of actuarial survival revealed that mortality was highest during the first 6 months after presentation (19% mortality). Survival declined more gradually thereafter and was 70% at 2 years, 64% at 5 years and 52% after 11.5 years. Age at initial presentation did not have any significant impact on survival. However, left ventricular end-diastolic pressure greater than 25 torr was associated with a significantly increased mortality rate (p less than 0.05). Early cardiac transplantation should be considered in patients with markedly elevated left ventricular end-diastolic pressure or complex atrial or ventricular arrhythmias. PMID- 1858678 TI - Effects of immunosuppressive therapy in biopsy-proved myocarditis and borderline myocarditis on left ventricular function. AB - Twenty patients with decreased left ventricular (LV) function and endomyocardial biopsy-proved myocarditis (9 patients) or borderline myocarditis (11 patients) were studied to determine whether these 2 histologic subsets of patients with inflammatory heart disease differed in their response to a 6- to 8-week course of immunosuppressive therapy. All patients received a regimen of prednisone, 1.0 mg/kg/day, and azathioprine, 1.5 mg/kg/day, followed by repeat endomyocardial biopsy and reevaluation of LV function. LV function improved significantly in the group with borderline myocarditis, as assessed by LV stroke work--end-diastolic volume ratio (0.26 +/- 0.17 to 0.54 +/- 0.31 kg.m.ml-1, p less than 0.02), heart rate corrected velocity of circumferential shortening (0.49 +/- 0.30 to 0.80 +/- 0.29 circ.s-1, p less than 0.05), and LV ejection fraction (0.30 +/- 0.15 to 0.47 +/- 0.13, p less than 0.05). LV end-diastolic and end-systolic volume indexes also decreased significantly from 129 +/- 40 to 94 +/- 38 (p less than 0.05) and 90 +/- 37 to 49 +/- 26 ml (p less than 0.02), respectively. No significant change in these indexes of LV function or volume occurred in the myocarditis group. Whereas salutory improvements in cardiac output and filling pressures were found in both groups, objective improvement in LV function assessed by complementary indexes of contractility was greatest in the borderline myocarditis group. It is concluded that short-term immunosuppressive therapy improves LV contractile function and appears to be associated with regression of ventricular dilatation in patients with borderline myocarditis to a greater extent than patients with myocarditis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858680 TI - Principles and practice of coronary thrombolysis and conjunctive treatment. PMID- 1858679 TI - Left ventricular filling abnormalities in asymptomatic morbid obesity. AB - Indexes of left ventricular (LV) diastolic filling were measured by pulse Doppler echocardiography in 16 asymptomatic morbidity obese patients presenting for bariatric surgery and were compared with an age- and sex-matched lean control population. No patient had concomitant disorders known to affect diastolic function. All patients had normal systolic function. LV wall thickness and internal dimension were measured in order to calculate LV mass. Fifty percent of morbidly obese patients had LV diastolic filling abnormalities as assessed by the presence of greater than or equal to 2 abnormal variables of mitral inflow velocity. The ratio of peak early to peak late (atrial) filling velocity was significantly decreased in obese compared with control patients (1.16 +/- 0.26 vs 1.66 +/- 0.30, p less than 0.001). The peak velocity of early LV diastolic filling was significantly reduced in obese patients (75 +/- 15 vs 98 +/- 19 cm/s, p less than 0.001). The atrial contribution to stroke velocity as assessed by the time-velocity integral of late compared with total LV diastolic filling was significantly increased in obese patients (36 +/- 7 vs 27 +/- 4%, p less than 0.001). Obese patients had significantly increased LV mass (214 +/- 45 vs 138 +/- 37 g, p less than 0.001), even when corrected for body surface area (95 +/- 16 vs 76 +/- 16 g/m2, p less than 0.002). However, increased LV mass did not correlate with indexes of abnormal diastolic filling in obese patients. These data suggest that abnormalities of diastolic function occur frequently in asymptomatic morbidly obese patients and may represent a subclinical form of cardiomyopathy in the obese patient. PMID- 1858681 TI - Immunosuppressive therapy and lipoprotein abnormalities after cardiac transplantation. PMID- 1858682 TI - Myocardial malondialdehyde and uric acid release after short-lasting coronary occlusions during coronary angioplasty: potential mechanisms for free radical generation. PMID- 1858683 TI - Waking up exhausted as risk indicator of myocardial infarction. PMID- 1858684 TI - A new noninvasive method for estimation of pulmonary arterial pressure in mitral stenosis. PMID- 1858685 TI - Evolution of the endocardial fibrotic process in endomyocardial fibrosis. PMID- 1858686 TI - Incidence of renal dysfunction in adults with cyanotic congenital heart disease. PMID- 1858687 TI - Usefulness of physical exercise for maintaining smoking cessation in women. PMID- 1858688 TI - Cardiac transplant waiting lists, donor shortage and retransplantation and implications for using donor hearts. PMID- 1858689 TI - Noninvasive estimation of left ventricular contractile state and afterload in normal newborn infants. PMID- 1858690 TI - Transesophageal echocardiographic characterization of pulmonary vein flow not due to atrial contraction or mitral regurgitation. PMID- 1858691 TI - Dilution of potent drugs. PMID- 1858692 TI - What are people really eating? The relation between energy intake derived from estimated diet records and intake determined to maintain body weight. AB - Two hundred sixty-six free-living human volunteers, 21-64 y old, were trained by dietitians to record daily their food intake for at least 7 d. Subsequently, they were fed diets of conventional foods adjusted in amounts to maintain their body weight for greater than or equal to 45 d. Comparing their estimated energy intake with the intake determined to maintain weight yielded mean differences of 2365 and 1792 kJ (565 and 428 kcal) in men and women, respectively, representing an underreporting of 18%. Twenty-two individuals (8%) overestimated and 29 (11%) were accurate to within 419 kJ (100 kcal) of their maintenance requirement. The remaining 215 individuals (81%) reported their habitual intake at 2930 +/- 1586 kJ (700 +/- 379 kcal) below that subsequently determined as their maintenance requirement. These findings suggest caution in the interpretation of food consumption data. PMID- 1858693 TI - Body composition of low-birth-weight infants determined by using bioelectrical resistance and reactance. AB - We tested the hypothesis that bioelectrical resistance and reactance are indices of total body water (TBW) and extracellular water (ECW), respectively. Infants less than 2500 g in birth weight were studied while less than 24 h old and at 4-7 d of age. TBW (n = 32) was measured by H2(18)O dilution and ECW (n = 34), by bromide dilution. Measurements were made by using an impedance plethysmograph from each of four electrode pairs. Bioelectrical resistance correlated inversely with TBW (r = -0.683). When body weight and crown-heel length were factored into the equation, the correlation improved (r = 0.953). Bioelectrical reactance correlated inversely with ECW (r = -0.707). When body weight and surface area were factored into the equation the correlation improved (r = 0.882). We conclude that bioelectrical resistance and reactance are good indices of TBW and ECW, respectively. However, the ability to resolve small changes in body-water compartments when confined to the intraluminal or other third spaces remains questionable, particularly for single subjects. PMID- 1858694 TI - Changes in body weight, body composition, and energy intake in women fed high- and low-fat diets. AB - The effects of a 20%-fat diet (LF) on total body weight, lean body weight, and adiposity were studied in 18 premenopausal women with body mass index (BMI) of 18 44. Subjects were fed a 37%-fat (HF) control diet for 4 wk followed by the LF diet for 20 wk. Total body weight, lean body weight, and fat weight were measured at the end of the HF and LF dietary periods by hydrostatic weighing. Despite adjustments in energy intake to maintain weight throughout the study, subjects exhibited a 2.8% decrease in total body weight (P less than 0.0006), an 11.3% decrease in fat weight (P less than 0.0001), and a 2.2% increase in lean body weight (P less than 0.0149) by the end of the LF period. Similar changes were observed in obese (BMI greater than 30) and non-obese women (BMI less than 30). By the end of the LF period, energy intake had increased significantly in comparison with the HF diet (119% of the HF intake, P less than 0.0001). Results could not be explained by changes in daily activity levels and suggest that macronutrient composition plays a role in energy requirements for weight maintenance. PMID- 1858695 TI - Children's food preferences and genetic sensitivity to the bitter taste of 6-n propylthiouracil (PROP). AB - Genetic sensitivity to bitter taste may be associated with preference or rejection of some foods by children. Thirty-four children aged 5-7 y participated in the following assessments: a threshold test for 6-n-propylthiouracil (PROP), a scaling test to determine PROP sensitivity above threshold concentrations, a taste test of 11 foods and beverages with two methods of assessing preference (order of food selection and hedonic rating), and a verbally administered food preference questionnaire. The 30 children who completed these tests successfully were classified as nontasters or tasters based on their PROP thresholds as well as their suprathreshold PROP functions. Analysis of variance showed significant differences in acceptance of cheese and milk for the two taste groups on one of the three preference tasks, selection of foods in order of preference. Tasters selected cheese later than did nontasters, suggesting that they like it less. Tasters selected milk earlier than did nontasters, suggesting that they like it more. PMID- 1858696 TI - Fluoxetine's effect on weight loss in obese subjects. AB - Forty-five obese subjects with a mean weight of 102.9 kg and a body mass index (in kg/m2) of 37.6 were randomly assigned to a fluoxetine-diet group (n = 23) or a placebo-diet group (n = 22) for 52 wk. At week 29, 14 subjects on fluoxetine who completed the study attained their maximum weight loss of 12.4 kg, an amount significantly greater than the maximum weight loss of 4.5 kg for the 16 on placebo who completed the study. The fluoxetine group's significantly greater mean weight loss continued through week 45. However, those on fluoxetine regained a mean of 4.2 kg from their lowest weight (P less than 0.001) whereas the placebo group did not. By the end of the study, each group weighed significantly less than they did at baseline (fluoxetine: -8.2 kg; placebo: -4.5 kg; P less than 0.05) although the difference between groups was no longer significant (P greater than 0.05). Several factors were considered as possible causes for the regain with fluoxetine. PMID- 1858697 TI - Comparison of three species of fish consumed as part of a Western diet: effects on platelet fatty acids and function, hemostasis, and production of thromboxane. AB - This study examined the effect of the consumption of moderate amounts of three species of fish on platelet fatty acid profile (PFA), bleeding time (BT), platelet aggregation, and ex vivo production of thromboxane B2 (TXB2). Twenty three healthy, young men consumed 200 g/d of Dover sole. Chinook salmon, and sablefish for 18 d in a three-way crossover design as part of a Western diet. Salmon and sablefish compared with sole caused significant increases in the eicosapentaenoic acid content of the PFA (P = 0.002). BT increased moderately when salmon diets were consumed (P = 0.06). Platelet aggregation decreased with collagen as an agonist on sablefish diets (P = 0.03) and with ADP as an agonist on salmon and sablefish diets (P = 0.04). TXB2 concentrations decreased moderately on sablefish and salmon diets (P = 0.06). Certain species of fish when consumed in reasonable amounts as part of a Western diet may cause modestly positive effects on platelet function. PMID- 1858698 TI - Fatty acid composition of subcutaneous adipose tissue and diet in postmenopausal US women. AB - The distributions of fatty acids in subcutaneous-adipose-tissue aspirates and their relation to intake as assessed by a semiquantitative food-frequency questionnaire were investigated in 115 postmenopausal US women free from cancer. Percentages of fatty acids in adipose tissue were significantly correlated with the percentage of total fat intake for polyunsaturated fatty acids (Spearman correlation = 0.37), n-3 fatty acids of marine origin (Spearman correlation = 0.48), and trans fatty acids (Spearman correlation = 0.51) but not for saturated and monounsaturated fatty acids. Correlations were somewhat stronger in 78 women with stable weight over the 6 mo before fat aspiration. These data suggest that intakes of polyunsaturated fatty acids, including n-3 fatty acids, and trans fatty acids are reflected in the adipose tissue but that intakes of saturated and monounsaturated fatty acids are not. The data also provide further support for the validity of the food-frequency questionnaire in the assessment of fat intake. PMID- 1858699 TI - Platelet aggregation in humans is affected by replacement of dietary linoleic acid with oleic acid. AB - The effect of concentrations of linoleic acid (LA) on platelet aggregation was measured in seven healthy adult males. Subjects were randomly divided into two groups; these groups were fed natural food diets of identical composition except that one was high in LA (11.5% of energy) and low in oleic acid (OA) (7.4% of energy), the other was low in LA (4.5% of energy) and high in OA (15.7% of energy). The thresholds of ADP- and collagen-induced platelet aggregation were increased significantly by the high LA diet even though the intake of total fat and saturated fatty acids did not differ in these diets. PMID- 1858700 TI - Reassessment of trans fatty acid availability in the US diet. AB - This report updates our 1984 estimate of the amount of trans fatty acids available for consumption in the US diet, namely 7.6 g.person-1.d-1, for 1989. Compared with 1984 data, we found essentially no change in 1989 for the per capita availability of trans fatty acids from total food service fats and oils. The 1989 value we obtained for industrial fats and oils is somewhat higher than the value we reported for 1984, in part because more complete data were available for 1989. In contrast, however, since 1984 the per capita availability of trans fatty acids from household salad and cooking oils, household shortenings, and all margarines and spreads (retail, food service, and industrial) has decreased. Overall, our reassessed (1989) value for total trans fatty acid availability is 8.1 g.person-1.d-1, which is similar to our original estimate. This total may increase slightly (approximately 0.3 g.person-1.d-1) as a result of the recent switch by many establishments from the use of tallow to partially hydrogenated vegetable oils for frying. PMID- 1858701 TI - Methionine kinetics and balance at the 1985 FAO/WHO/UNU intake requirement in adult men studied with L-[2H3-methyl-1-13C]methionine as a tracer. AB - The upper range of the requirement for methionine plus cystine in healthy adults was proposed in 1985 by FAO/WHO/UNU to be 13 mg.kg body wt-1.d-1. To explore the validity of this estimate, five healthy, young adult men were given for 7 d a diet based on an L-amino acid mixture supplying 13 mg methionine.kg-1.d-1 (87 mumol.kg-1.d-1) without cystine. Constant intravenous infusions of L-[2H3-methyl 1-13C]methionine were given on days 5 and 7 while subjects were in the fed and postabsorptive states, respectively. Estimates were made of methionine oxidation, and daily methionine balance was derived from the intake-oxidation data. For the five subjects, methionine balances were -0.9, +0.7, +3.5, -3.1, and -3.8 mg kg 1.d-1, or -6, +5, +23, -21, and -26 mumol.kg-1.d-1. These findings lead to the conclusion that the upper range of the requirement for methionine plus cystine probably exceeds 13 mg.kg-1.d-1 in healthy young adults. The implications of this conclusion for establishing an appropriate amount of sulfur amino acids in an amino acid requirement pattern for adults is discussed. PMID- 1858702 TI - Methionine kinetics in adult men: effects of dietary betaine on L-[2H3-methyl-1 13C]methionine. AB - The effects of a daily 3-g supplement of betaine on kinetic aspects of L-[2H3 methyl-1-13C]methionine (MET) metabolism in healthy young adult men were explored. Four groups of four subjects each were given a control diet, based on an L-amino acid mixture supplying 29.5 and 21.9 mg.kg-1.d-1 of L-methionine and L cystine for 4 d before the tracer study, conducted on day 5 during the fed state. Two groups received the control diet and two groups received the betaine supplement. Tracer was given intravenously (iv) or orally. The transmethylation rate of MET (TM), homocysteine remethylation (RM), and oxidation of methionine were estimated from plasma methionine labeling and 13C enrichment of expired air. RM tended to increase (P = 0.14) but the TM and methionine oxidation were significantly (P less than 0.05) higher after betaine supplementation when estimated with the oral tracer. No differences were detected with the intravenous tracer. Methionine concentration in plasma obtained from blood taken from subjects in the fed state was higher (P less than 0.01) with betaine supplementation. These results suggest that excess methyl-group intake may increase the dietary requirement for methionine. PMID- 1858703 TI - Branched-chain amino acid interactions with reference to amino acid requirements in adult men: valine metabolism at different leucine intakes. AB - We explored whether the oxidation of valine and by implication the physiological requirement for this amino acid are affected by changes in leucine intake over a physiological range. Six young adult men received, in random order, four L-amino acid-based diets for 5 d supplying either 20 or 10 mg valine.kg body wt-1.d-1, each in combination with 80 or 40 mg leucine.kg-1.d-1. On day 6 subjects were studied with an 8-h continuous intravenous infusion of [1-13C]valine (and [2H3]leucine) to determine valine oxidation in the fasted state (first 3 h) and fed state (last 5 h). Valine oxidation in the fasted state was similar among all diets but was lower (P less than 0.05) in the fed state for the 10 vs 20 mg valine.kg-1.d-1 intake. Leucine intake did not affect valine oxidation. Mean daily valine balance approximated +1.3 mg.kg-1.d-1 for the 20-mg intake and -1.6 mg.kg-1.d-1 for the 10-mg intake. These findings support our previously suggested mean valine requirement estimate of approximately 20 mg.kg-1.d-1. PMID- 1858704 TI - Branched-chain amino acid interactions with reference to amino acid requirements in adult men: leucine metabolism at different valine and isoleucine intakes. AB - Recent estimates of the leucine requirement of adult men based on 13C-tracer studies are substantially higher than those proposed by FAO/WHO/UNU (1985). To explore whether leucine oxidation and requirements are affected by the dietary amount of valine. 11 healthy young adult men received, in random order, for 5 d, one of four L-amino acid diets providing 40 or 15 mg leucine.kg-1.d-1 together with variable amounts mg.kg-1.d-1 of valine and isoleucine in the following combinations (Val:Ile): 80:62 and 20:62 (six subjects; phase 1); 20:62 and 20:20 (five subjects, phase 2). On the morning of day 6, a continuous intravenous infusion of L-[1-13C]leucine was given for 7-8 h; the subject was in the fasting state for the initial 2.5 or 3 h and in the fed state for the remainder of the time. Also, [2H3]leucine was added to the diet. Leucine oxidation was similar for all diet groups in the fasted state. During the fed state, leucine oxidation was not affected by the Val:Ile pattern. Thus, changes in the pattern of branched chain amino acid intake within a physiological range do not affect isotopically derived estimates of the leucine requirement. PMID- 1858705 TI - Proline metabolism in adult male burned patients and healthy control subjects. AB - Postabsorptive proline flux, oxidation, and endogenous biosynthesis were determined in five severely burned intensive-care-unit patients (mean age 27 y) and in six healthy, young-adult control subjects. Continuous primed, intravenous, 160-min, dual stable-isotope-tracer infusions of L-[1-13C]proline and L-[methyl 2H3]leucine were used in conjunction with measurement of plasma proline concentration and 24-h urinary hydroxyproline output. Burn patients, compared with normal individuals, demonstrated a doubling in proline and leucine flux (P less than 0.01 for both findings), a threefold enhancement of proline oxidation (P less than 0.05), a trend toward decreased proline synthesis, and a 37% reduction in plasma proline concentrations (P less than 0.05). Further, the injured group, unlike the control group, was in a distinct negative body proline balance, as proline oxidation greatly exceeded endogenous proline biosynthesis (P less than 0.01). These studies indicate that significant proline deficits may evolve during the postabsorptive period in severely burned patients and that an exogenous supply of proline might benefit the nitrogen economy of the traumatized patient. PMID- 1858706 TI - Calcium and phosphorus deficiencies affect mineral distribution in neonatal miniature piglets. AB - Current efforts to monitor the mineral status of preterm infants fed human milk may not provide sufficient information on the distribution of body minerals. To investigate the body distribution of calcium and phosphorus during various degrees of mineral deficiency, neonatal miniature piglets were raised for 2 wk on diets differing only in calcium and phosphorus. Groups A, B, and C were fed 100%, 60%, and 20%, respectively, of the recommended amounts of calcium and phosphorus that, when adjusted for rates of growth, approximated the range of dietary intakes of preterm infants. Group C manifested biochemical and body-composition evidence of mineral deficiency when compared with group A: lower serum phosphorus; higher serum alkaline phosphatase activity; less fat-free tissue, calcium, and phosphorus in tibiae, vertebrae, and whole carcasses. Neonatal miniature piglets are useful for studying mineral deposition during mineral deficiency in preterm infants. PMID- 1858707 TI - Influence of calcium intake and growth indexes on vertebral bone mineral density in young females. AB - This cross-sectional study examined the relationship between current calcium intake and vertebral bone mineral density (V-BMD) in 49 healthy Caucasian adolescent females aged 8-18 y. The ability of current calcium intake to account for the variance in V-BMD in this population was compared with that seen with weight, height, maturational age (determined by the Tanner Sexual Maturity Rating), chronological age, and total energy expenditure. Calcium intake was determined from the mean of 4-d, food-intake records. Average vertebral bone mineral density from L1-L4 was measured by dual x-ray absorptiometry. A multiple regression model revealed that 81% of the variance in V-BMD was described by maturational age, chronological age, and calcium intake, with all representing significant predictors of bone mineral density (P less than 0.0001, 0.005, 0.04, respectively). This study supports the hypothesis that better calcium nutrition during adolescence may optimize, within genetic boundaries, peak bone mass. PMID- 1858708 TI - Cholestyramine and oropharyngeal cancers. PMID- 1858709 TI - Platelet response to intravenous lipid emulsions. PMID- 1858710 TI - Effect of beta-carotene on lymphocyte subpopulations in elderly humans. PMID- 1858711 TI - Child welfare: the phantom of the health care system. PMID- 1858712 TI - Resident and nurse practitioners: responding to education and patient care needs. PMID- 1858713 TI - Priorities in academic pediatrics. PMID- 1858714 TI - Thumb-sucking. PMID- 1858715 TI - The 80-hour workweek and residency programs: closing arguments. PMID- 1858716 TI - Child sexual abuse and human immunodeficiency virus transmission. PMID- 1858717 TI - Anal fissure produced by examination for sexual abuse. PMID- 1858718 TI - Gilding the lily. PMID- 1858719 TI - Jack Metcoff festschrift. PMID- 1858720 TI - Zinc deficiency. A public health problem? AB - Zinc deficiency occurs in individuals and populations whose diets are low in sources of readily bioavailable zinc such as red meat, and high in unrefined cereals that are rich in phytate and dietary fibers. Dietary zinc deficiency was described nearly three decades ago among the poor of the Middle East. It is now known to occur in children and adolescents from widely diverse areas including Egypt, Iran, Turkey, China, Yugoslavia, Canada, and the United States; and among pregnant women from Iran, Turkey, the United Kingdom, Australia, and the United States. Major manifestations include retarded growth and development and an increased incidence of pregnancy complications. Other manifestations may include suppressed immunity, poor healing, dermatitis, and impairments in neuropsychological functions. Precise information as to the numbers of people affected by dietary zinc deficiency is not available. Even so the nature of diets associated with zinc deficiency suggests that mild deficiency is common in some populations. PMID- 1858721 TI - Paleonephrology and reflux nephropathy. From the 'big bang' to end-stage renal disease. AB - Urinary tract infections, in association with ureteral reflux or dysperistalsis, may lead to invasive renal parenchymal infection and residual scarring (reflux nephropathy). Such infections in infants are often not diagnosed during the acute phase. Late sequelae of reflux nephropathy include hypertension, proteinuria, or chronic renal failure. The latter may eventuate in the subset of patients with urinary tract infection and unilateral reflux extending to a solitary kidney or bilateral reflux. Proteinuria may herald the inexorable progression of glomerular sclerosis in patients destined to progress to end-stage renal disease, despite the absence of further recurrences of urinary tract infections. The mechanism of progression is probably similar to that occurring in other forms of chronic, diffuse parenchymal renal disease, which all have similar alterations in glomerular hemodynamics (an increase in glomerular capillary flow, pressure, and filtration). The consequent hyperfiltration per nephron may be related to the level of dietary protein intake or to some derivative of the protein load. Hyperfiltration appears to recapitulate the presumed renal hemodynamic response to the relatively high level of episodic meat consumption by paleolithic hunter gatherers. A prudent therapeutic intervention in children with progressive reflux nephropathy may be a proportional reduction in protein intake. PMID- 1858722 TI - X-linked hypophosphatemia. Genetic and clinical correlates. AB - X-linked hypophosphatemia is a hereditary form of rickets that results from an isolated renal tubular wasting of phosphate. The clinical features unique to this disorder, and the recent advances in our understanding of vitamin D metabolism and molecular genetics in X-linked hypophosphatemia are reviewed. Finally, a succinct critique of the controversial treatment modalities round up this review. PMID- 1858723 TI - Studies in fetal malnutrition. AB - Fetal malnutrition, a worldwide problem, is accompanied by varying degrees of lifelong morbidity for the child. Only 25% of fetal malnutrition is accomplished by maternal risk factors known to cause intrauterine growth retardation (ie, chronic hypertension, advanced diabetes mellitus, or severe preeclampsia). If the malnourished fetus could be detected early in pregnancy, nutritional intervention might be successful in improving fetal growth rate and in avoiding the morbidity due to malnutrition. This communication reviews the almost 40 years of studies by Jack Metcoff, MD, and coworkers to unravel the causes of fetal malnutrition and their efforts to prevent it. PMID- 1858724 TI - Partial hypoparathyroidism. A variant of transient congenital hypoparathyroidism. AB - We encountered three children who had neonatal hypocalcemia followed by a period of normocalcemia and recurrence of hypocalcemia later in childhood. They were full-term infants with normal birth weights who developed hypocalcemia within the first 48 hours after birth. The hypocalcemia resolved in 1 week, 3 months, and 14 months in the three patients. The recurrences of hypocalcemia occurred at 4, 7, and 12 years of age. Their plasma parathyroid hormone concentrations were consistently low but detectable. We suggest that partial hypoparathyroidism is the underlying abnormality in these patients and that neonatal hypocalcemia in otherwise healthy infants indicates the need for calcium measurements during childhood and adolescence. PMID- 1858725 TI - Clinic-based intervention to promote literacy. A pilot study. AB - Educational research has shown that children become literate more easily if their parents read to them. A clinic-based program was designed to encourage early book use among parents of children at risk. It included (1) waiting room readers, (2) guidance about literacy development, and (3) provision of children's books at each visit. Seventy-nine parents of children aged 6 to 60 months were interviewed. Parents who had previously received a book were more likely to report looking at books with their children or that looking at books was a favorite activity (adjusted odds ratio, 4.05). This association was strongest among parents receiving Aid to Families With Dependent Children (odds ratio, 7.8). This preliminary study suggests that pediatricians can play a role in enriching children's early literacy environments, especially for children at high risk of school failure. PMID- 1858726 TI - Immunization response varies with intensity of acute lymphoblastic leukemia therapy. AB - Twenty-four children receiving maintenance chemotherapy for acute lymphoblastic leukemia were given booster doses of tetanus-diphtheria combined toxoids. One month later, 19 of the 24 children were given Haemophilus influenzae B oligosaccharide-cross-reacting material conjugate vaccine. Following immunization, all patients had protective antibody titers against tetanus, 92% had protective antidiphtheria titers, and 84% had protective titers against H influenzae. Preimmunization titers, postimmunization titers, and response to immunization varied according to the intensity of therapy. There was no correlation with duration of therapy or quantitative hematologic values in the peripheral blood. These observations support the recommendation that children treated for acute lymphoblastic leukemia should be immunized against H influenzae B. PMID- 1858727 TI - Response of 7- to 15-month-old infants to sequential immunization with Haemophilus influenzae type b-CRM197 conjugate and polysaccharide vaccines. AB - OBJECTIVE: To evaluate the immunologic potential of infants 7 to 15 months of age to respond to Haemophilus influenzae type b polysaccharide vaccine following immunization with H influenzae b oligosaccharide-CRM197 conjugate vaccine. STUDY DESIGN: One hundred seventy-one infants, aged 7 to 15 months, were consecutively and alternatively assigned to one of three immunization protocols. Group 1 (n = 71) received three doses of H influenzae b oligosaccharide-CRM197 conjugate vaccine, group 2 (n = 47) received two doses of H influenzae b oligosaccharide CRM197 conjugate vaccine followed by one dose of H influenzae type b polysaccharide vaccine, and group 3 received one dose of H influenzae b oligosaccharide-CRM197 conjugate vaccine followed by two doses of H influenzae type b polysaccharide vaccine. Immunizations were given on day 0 and at 2 months and 6 months. Anti-H influenzae type b polysaccharide antibody levels were measured on day 0 and 2, 3, 6, 7, and 12 months after the study began. RESULTS: Haemophilus influenzae type b polysaccharide vaccine given as a second dose stimulated an antibody rise but did so less effectively than H influenzae b oligosaccharide-CRM197 conjugate vaccine. Two doses of H influenzae b oligosaccharide-CRM197 conjugate vaccine were highly immunogenic; geometric means were 31 and 35 micrograms/mL in the 7- to 11-month and 12- to 15-month age groups, respectively. Following two doses of H influenzae b oligosaccharide CRM197 conjugate vaccine, both immunization protocols resulted in (1) equally high geometric mean antibody levels 1 month after immunization and (2) similar geometric mean antibody levels 6 months after immunization. CONCLUSIONS: Haemophilus influenzae b oligosaccharide-CRM197 conjugate vaccine induces antibody levels that would be expected to protect infants from initial invasion and primes the immune system for an anamnestic response. Our data indicate that if a booster immunization is needed, H influenzae type b polysaccharide vaccine could be an alternative to H influenzae b oligosaccharide-CRM197 conjugate vaccine. PMID- 1858728 TI - Transfusion therapy in neonates. AB - Infants, particularly those who were very small premature neonates, are among the most common of all patient groups to undergo extensive transfusion. It is estimated that approximately 300,000 neonates undergo transfusions annually. Most infants who undergo transfusion are exposed to multiple blood donors, and although each exposure poses only a small risk, the potential for adverse effects of multiple transfusions is not variable, and based on scanty scientific information. For the most part, controlled scientific studies have not been performed to clearly establish the indications for the transfusion of blood components to neonates. Considering these limitations, guidelines are offered for the transfusion of red blood cells, platelets, and neutrophils into neonates. PMID- 1858729 TI - Testing the psychogenic vomiting diagnosis. Four pediatric patients. AB - We treated four patients with chronic vomiting during childhood in whom a tentative diagnosis of psychogenic vomiting was made after an extensive evaluation. In each case, the diagnosis was reconsidered during the course of treatment, as observations about the patients and their response to interventions accumulated. In three instances, these observations did not fit those expected if the diagnosis of psychogenic vomiting was correct. This led to a reexamination of the organic evaluation and the discovery of an undiagnosed organic contribution to the vomiting. In the fourth patient, gastric emptying studies confirmed that there was a strong psychological contribution to the vomiting, and helped to more carefully define this contribution. Family and individual psychotherapy and treatment were aided by the greater clarity in diagnosis. PMID- 1858730 TI - A practical guide to successful breast-feeding management. AB - It is often difficult for new mothers to know whom to approach for the necessary guidance and practical problem solving required for successful long-term lactation. Although obstetricians are familiar with the care of the breast, they may not maintain the degree of postpartum follow-up necessary to ensure its proper function nor is it their responsibility to ensure that the infant receives proper nourishment. Pediatricians are expected to offer advice and information regarding not only the advantages and disadvantages of breastfeeding but also practical management of this art. We provide a guide for practitioners who wish to assist breast-feeding mothers and their infants. PMID- 1858731 TI - Use of infant walkers. Board of Trustees, American Medical Association. AB - Infant walkers are used by many parents because of the convenience they provide in keeping children occupied. Unfortunately, parents may develop a false sense of security that leads to diminished vigilance over the safety of their infant. Although most injuries that result from walkers are minor, serious trauma from head injuries, lacerations, and burns does occur occasionally. The American Medical Association recommends that physicians counsel parents on the risk of injury that can occur from the use of infant walkers and inform parents that these devices do not either promote bipedal ambulation or offer a substitute for careful parental supervision. PMID- 1858732 TI - Rice solution and World Health Organization solution by gastric infusion for high stool output diarrhea. AB - We sought to determine the efficacy of three different types of treatment in children with acute diarrhea who, during the oral rehydration period, had high stool output (greater than 10 mL/kg per hour). Sixty-six children, aged 1 to 18 months, with an average stool output of 22.6 mL/kg per hour were randomly distributed into three groups: group 1 received a rice flour solution, group 2 received the World Health Organization rehydration solution by gastric infusion, and group 3 continued to receive this solution orally. In all three groups, a decrease in stool output was observed, with the higher decrease observed in group 1 patients. Such a decrease facilitated rehydration of all 22 patients in group 1 (100%) in 3.3 +/- 1.5 hours, 16 (73%) in group 2 in 4.3 +/- 2.1 hours, and 15 (69%) in group 3 in 4.9 +/- 2.0 hours. No complications were observed. These data indicate that the rice flour solution is effective in children with high stool output diarrhea. PMID- 1858733 TI - Low serum calcium and high parathyroid hormone levels in neonates fed 'humanized' cow's milk-based formula. AB - We previously suggested that "late" neonatal hypocalcemia is related to a low calcium-phosphorus ratio of current cow's milk-based formula compared with human milk. However, there are no longitudinal studies of ionized calcium and parathyroid hormone concentrations in neonates receiving formulas with varying Ca/P ratios. Sixty-nine term neonates were studied through 2 weeks of age, and formula-fed neonates were randomized at birth to receive formula with molar ratios of 0.9, 1.2, or 1.4. Serum phosphate concentrations on days 2 and 6 of age were higher, and ionized calcium levels lower on days 6 and 14, in formula-fed vs human milk-fed neonates. Serum intact parathyroid hormone level increased between days 2 and 6 in formula-fed neonates compared with a decrease in human milk-fed neonates. Serum parathyroid hormone level on day 6 correlated with phosphorus intake among formula-fed neonates. No differences were noted in serum mineral or hormone levels among formula-fed groups. We speculate that the lowering of serum ionized calcium concentrations in neonates fed a modern "humanized" cow's milk formula may be a factor in late neonatal hypocalcemia. PMID- 1858734 TI - Evaluation of intraosseous vs intravenous antibiotic levels in a porcine model. AB - OBJECTIVES: To compare intraosseous vs intravenous routes of administration and their effects on serum levels of four antibiotics in an animal model. DESIGN: Prospective controlled study comparing two routes of drug administration. SETTING: Research laboratories of a large pharmaceutical company. PARTICIPANTS: Twenty male and female domestic swine weighing 10 to 20 kg. INTERVENTIONS: The animals were anesthetized and treated with controlled ventilation. The animals were divided into one of four groups: (1) intravenous and intraosseous cefotaxime sodium (50 mg/kg), (2) intravenous and intraosseous chloramphenicol sodium succinate (25 mg/kg), (3) intravenous and intraosseous vancomycin hydrochloride (15 mg/kg), or (4) intravenous and intraosseous tobramycin sulfate (2.5 mg/kg). There was a 24-hour clearance period for groups 1 and 2 and a 48-hour clearance period for groups 3 and 4. Serum drug levels were measured at 1, 15, 30, 45, 60, 90, and 120 minutes after intravenous and intraosseous administration of the respective antibiotics. Control and treated tibias were sampled for drug levels at the end of the experiment. MEASUREMENTS AND MAIN RESULTS: - Peak serum concentrations for intravenously administered antibiotics were within the therapeutic range. Peak serum levels after intravenous and intraosseous administration were 102 and 82 mg/L, respectively for cefotaxime; 13.9 and 6.3 mg/L, respectively, for chloramphenicol; 24.5 and 3.8 mg/L, respectively, for vancomycin; and 7.1 and 1.3 mg/L, respectively, for tobramycin. CONCLUSIONS: Cefotaxime may be administered intraosseously when intravenous access is not possible. We cannot recommend chloramphenicol or vancomycin for intraosseous administration, because serum levels were not comparable with those following intravenous administration. Findings with tobramycin suggested a lack of achievement of serum levels comparable with those following intravenous administration. PMID- 1858735 TI - Gallstone formation after rapid weight loss: a prospective study in patients undergoing gastric bypass surgery for treatment of morbid obesity. AB - The present study evaluated the incidence of gallstone formation in 105 morbidly obese patients undergoing rapid weight loss after proximal gastric bypass surgery. Intraoperative ultrasonography demonstrated gallstones in 20 (19%) and gallbladder sludge in four (4%) patients. Eighty-one patients had a normal gallbladder ultrasound. After bariatric surgery, these patients were followed prospectively with periodic gallbladder ultrasound examinations. At 6 months, gallstones had developed in 36% and gallbladder sludge in 13% of patients. These percentages remained relatively constant at 12 and 18 months. Body weight declined rapidly after surgery from a mean of 132.3 kg to 95.5, 87.0, and 84.0 kg at 6, 12, and 18 months, respectively. Gallstones developed significantly more often in the white race, and in women. No significant differences in age, body weight, percent ideal body weight, percent weight loss, or percent of excess body weight lost existed between patients who developed gallstones or sludge and those who did not. Patients who developed gallbladder sludge had less cholesterol and lower cholesterol saturation (1.25 +/- 0.42) in their gallbladder bile than persons who developed gallstones (2.00 +/- 0.79). Forty percent (13/32) of patients who developed gallstones became symptomatic; nine (28%) underwent elective cholecystectomy. An attempt to prevent gallstone formation during rapid weight loss appears warranted. PMID- 1858736 TI - Choledocholithiasis in cirrhotic patients: is endoscopic sphincterotomy the safest choice? AB - Of the 18 endoscopic sphincterotomies performed on 18 cirrhotic patients for choledocholithiasis, a mortality rate of 16.6% was registered. However, this figure can be limited to 6.6% if we take only successful sphincterotomies (15/18, 83.3%) into account. After closely reviewing relevant literature, it would appear that operative mortality in comparable cases is much higher. We therefore recommend that endoscopic sphincterotomy, despite higher mortality rates when compared to the general population, should be the initial choice of management of choledocholithiasis in cirrhotic patients. PMID- 1858737 TI - Preoperative and intraoperative fine needle aspiration cytology of pancreatic lesions. AB - The aim of the present study was to describe our experience from 1976 through 1988 with fine needle aspiration (FNA) cytology of pancreatic lesions in 90 patients. Fine needle aspirations were performed preoperatively under ultrasound guidance (USG) in 46 patients, under computed tomographic guidance (CTG) in seven patients, and intraoperatively in 37 patients. Based on histologic, cytologic, and clinical findings, final diagnoses were reached in 80 patients, of whom 62 had malignant pancreatic disease (MPD) and 18 had benign pancreatic disease (BPD). The accuracy of cytologic diagnoses was verified by histologic, cytologic, and clinical findings. In 62 patients with MPD, the cytologic findings suggested malignancy in 54 patients, suspected malignancy in five, and did not reveal malignancy in three patients. Among 18 patients with BPD, all of the cytologic findings were reported as benign. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for intraoperative FNA cytologic results were 96%, 100%, 100%, 91%, and 97%, respectively, and for USG FNA cytologic results were 94%, 100%, 100%, 78%, and 95%, respectively. No complications followed the procedure. CONCLUSIONS: Both transabdominal percutaneous imaging-guided and intraoperative FNA cytology of pancreatic lesions are simple, safe, and highly accurate methods in differentiation of benign from malignant pancreatic lesions. PMID- 1858738 TI - Relationship between glucose tolerance and quantitative changes of islet cells in chronic obstructive pancreatitis due to pancreatoduodenal cancer. AB - This study was conducted to clarify the relationship between indicators of preoperative glucose tolerance and quantitative changes of endocrine cells in the islet of Langerhans in patients with chronic obstructive pancreatitis due to pancreatoduodenal cancer. Twenty-one specimens of pancreatic tissue obtained from patients who underwent pancreatoduodenectomy or total pancreatectomy for pancreatoduodenal cancer were divided into four groups according to the degree of fibrosis (Grades 0-III). Islet cells in serial sections were stained immunohistochemically to determine the proportions of B-, A-, D-, and PP-cells in the islets of Langerhans. In patients with pancreatic tissue with the most severe fibrosis, of several preoperative glucose metabolism indices measured, it was found that the ratio of integrated value of change in serum insulin to that of serum glucose (sigma delta IRI:sigma delta BS) was significantly decreased. There was a significant positive correlation between proportion of B-cells, and both the ratio of change in insulin to that of glucose (delta IRI:delta BS) and sigma delta IRI:sigma delta BS. On the other hand, there was a significant negative correlation between proportion of A-cells and sigma delta IRI:sigma delta BS. The present data strongly suggest that it is possible to estimate the degree of fibrosis and to quantify changes of the islet cells prior to surgery in patients with obstructive pancreatitis due to pancreatoduodenal cancer by calculating these glucose metabolism indices, and that sigma delta IRI:sigma delta BS is a particularly useful index. PMID- 1858739 TI - Prognostic implications of the localization of carcinoma in the head of the pancreas. AB - Between 1974 and 1989, 411 patients with pathologically and anatomically proven carcinoma of the head of the pancreas underwent endoscopic retrograde cholangiopancreatography (ERCP). According to the localization of the tumor, these patients were divided into those with a cranially, centrally (periductally), caudally, or indeterminately localized tumor. In cranially localized tumors, extrahepatic metastases and vessel invasion were absent or resectable in 53% and 46%, respectively. The tumor was resectable in 41% of cases. If a patient with a cranially localized tumor could not be operated curatively for secondary reasons, the prognosis was better than for tumors with another localization. If there was unresectable vessel invasion and the tumor was not resectable, the 0% survival rate was reached at 33 months. Of the curatively operated patients, 26% were alive at 36 months after the start of complaints. Of the centrally or periductally localized tumors, there were no liver metastases in 73%. Extrahepatic metastases and vessel invasion were absent or resectable in 57% and 53%, respectively. The tumor was resectable in 48% of cases. If there was unresectable vessel invasion or the tumor was unresectable, the 0% survival rate was reached after 18 months. These tumors have maximal chances at curative resection. Of the curatively operated patients, 31% were alive at 36 months after the start of complaints. In caudally localized tumors, there were liver metastases in 59%, unresectable other abdominal metastases in 93%, unresectable vessel invasion in 91%, and the tumor was unresectable in 96%. In patients with an unresectable vessel invasion or an unresectable tumor, the 0% survival rate was reached after 33 months; 3% of these patients were operated curatively. Indeterminately localized tumors had liver metastases in 77%, unresectable extrahepatic metastases in 90%, unresectable vessel invasion in 95%, and the tumor was unresectable in 91%. Only one of the 44 patients (2%) could be operated curatively. PMID- 1858740 TI - Small bowel length in Crohn's disease. AB - The length of the small intestine in patients with Crohn's disease who are referred for surgery has not been well studied. In this report, 25 patients with Crohn's disease who were being operated on for the first time had their small intestine measured at the time of surgery. The mean length of small intestine in this group was 501 cm, which was not different from a group of patients without Crohn's disease who were being operated on for other problems. In the group of patients with Crohn's disease, as well as the entire group, there was a correlation between increasing height and longer small bowel length. No other parameters investigated, including weight, surface area, age, sex, and duration of disease, correlated with bowel length. The results of this study are somewhat encouraging to patients with Crohn's disease, since these patients do not start off with a shortened bowel prior to surgery. PMID- 1858741 TI - Endometriosis of the terminal ileum simulating the clinical, roentgenographic, and surgical findings in Crohn's disease. AB - A 38-yr-old nulliparous female presented with endometriosis of the terminal ileum which mimicked the clinical, roentgenographic, and surgical findings of Crohn's disease. The patient presented with diarrhea, right lower quadrant pain, fever, and significant weight loss. At surgery, the terminal ileum was inflamed, indurated, thickened, and angulated. Ileal endometriosis may be expected to simulate Crohn's disease, because intestinal endometriosis frequently produces local bowel inflammation, adhesions, stricture, and angulation. Ileal endometriosis should be carefully considered in the differential diagnosis of Crohn's disease in menstruating females who are nulliparous and have dysmenorrhea, dyspareunia, dyschezia, menometrorrhagia, or other perimenstrual symptoms. It is important not to mistake endometriosis for Crohn's disease because endometriosis has a different therapy. PMID- 1858742 TI - Crohn's colitis complicated by superimposed invasive amebic colitis. AB - The clinical characteristics and endoscopic appearance of inflammatory bowel disease (IBD) may be very similar to those of amebic colitis. Physicians, especially in areas in which amebiasis is endemic, are familiar with this difficulty. Moreover, in individual cases, it may even be impossible to distinguish between the two conditions, since stool specimens, bowel biopsies, and serological studies may be negative for Entamoeba histolytica, even in the presence of invasive amebic colitis. Invasive amebiasis may rarely be superimposed on IBD, which further complicates the issue. We report here a young patient with a 7-yr history of Crohn's colitis proven histologically who developed invasive amebic colitis during steroid and 6-mercaptopurine treatment for active disease. Stool specimens, mucosal biopsies, and serological studies were negative for E. histolytica, and the diagnosis was established on pathological examination of a surgically resected bowel. Anti-amebic therapy should be considered in endemic areas in cases of persistent IBD. PMID- 1858743 TI - Acinar cell carcinoma of the pancreas: a rare cause of left-sided portal hypertension. AB - Isolated splenic vein obstruction with left-sided portal hypertension is a rare clinical condition. Owing to the close relationship of the splenic vein and the pancreas, this rare phenomenon is usually secondary to pancreatic inflammation or neoplasm. Acinar cell carcinoma has long been recognized as a distinctive, rare type of pancreatic carcinoma. A case of isolated splenic vein obstruction with left-sided portal hypertension secondary to acinar cell carcinoma of the pancreas, which we are reporting here, is thought to the first documented in the literature. PMID- 1858744 TI - Carcinoid tumor of the common bile duct: evidence for its origin in metaplastic endocrine cells. AB - Carcinoid tumors of the extrahepatic bile ducts are extremely rare neoplasms. The authors report the case of a 36-yr-old male patient with a carcinoid tumor that arose in the common hepatic bile duct. The non-neoplastic mucosa showed areas of gastric and intestinal metaplasia that included scattered argyrophil endocrine cells. Since the normal mucosa of the bile ducts lacks the latter type of cells, this case provides evidence for the first time that carcinoid tumors of this anatomic site probably originate from metaplastic endocrine cells. PMID- 1858745 TI - A case of extragenital choriocarcinoma in the jejunum. AB - A case of extragenital choriocarcinoma which produces human chorionic gonadotropin (HCG) in the small intestine of a 48-yr-old Japanese women is reported. Only seven such cases have been reported. The patient complained of postprandial upper abdominal pain and vomiting of 5 months' duration. Nine years before, right upper lobectomy was performed because of lung undifferentiated carcinoma. Double-contrast examination of the small intestine showed irregular ulceration in the lower jejunum. Celiac angiography demonstrated a hypervascular tumor stain in the branch of the jejunal artery. The serum HCG level was elevated. Gynecological examination revealed nothing abnormal. A small intestinal neoplasm was diagnosed, and a partial resection of the jejunum was performed. Endoscopy on the operating table showed a large, irregularly shaped sessile ulcer. Histologically the tumor was diagnosed as choriocarcinoma, composed of syncytiotrophoblastic cells and cytotrophoblastic cells. Immunohistochemical staining for HCG was positive. No metastasis was present. Although extragenital choriocarcinoma in the small intestine is rare, it should be included in the differential diagnosis of small intestinal neoplasm. PMID- 1858746 TI - Primary squamous cell carcinoma of a gastric remnant. AB - A 77-yr-old male developed primary gastric squamous cell carcinoma 33 yr after gastric resection for peptic ulcer disease. At the time of diagnosis, he was being endoscopically followed for large irregular stomal polyps. Infiltrating squamous cell carcinoma with focal keratinization and stomal polypoid hypertrophic gastritis was found. Previous reports describe adenocarcinoma and adenosquamous carcinoma in gastric remnants. There are various theories as to how such a tumor may arise in this setting. PMID- 1858747 TI - Pill-esophagitis caused by nonsteroidal antiinflammatory drugs. AB - A case of meclofenamate-induced pill-esophagitis is reported, and the relevant literature is reviewed. The role of posture, amount of fluid chaser, esophageal obstruction or dysmotility, drug formulation, physical and chemical properties of the drug, and concomitant ingestion of alcohol, as well as the diagnosis and management of such cases, are discussed. PMID- 1858748 TI - Angiography in massive UGI bleeding--would you believe better than endoscopy? PMID- 1858749 TI - Helicobacter pylori and NSAIDS--more questions than answers. PMID- 1858750 TI - HIDA imaging in postcholecystectomy syndrome--clinical value or romancing the stone? PMID- 1858751 TI - Cholestasis, hypoprothrombinemia, and cefotaxime, or how to prolong a short story. PMID- 1858752 TI - Comment on editorial by Dr. Rogers. PMID- 1858753 TI - Congenital microgastria in an adult. PMID- 1858754 TI - Cost-effective way of removing gastrostomy tubes. PMID- 1858755 TI - Omeprazole-cyclosporin interaction. PMID- 1858756 TI - Post-endoscopy arterial oxygen desaturation and pulse oximetry. PMID- 1858757 TI - Prevalence and malignant potential of colorectal polyps in asymptomatic, average risk men. AB - Screening colonoscopy was performed on 119 asymptomatic elderly men with no other risk factors for colonic neoplasms. Ninety adenomas were detected in 49 (41%) subjects. Mean adenoma size was 6.5 mm, with 83 (92%) less than or equal to 10 mm. Forty-nine (54%) adenomas were located proximal to the splenic flexure, and 17 (19%) were classified as tubulovillous or villous. Moderate- to high-grade dysplasia was found in 29 (32%) adenomas and was associated with larger size (p less than 0.0001) and villous architecture (p = 0.0038). Two subjects harbored adenomas with invasive cancer. Seventy-one hyperplastic polyps were found in 40 (34%) subjects. The mean size of hyperplastic polyps was 3.4 mm, and 64 (90%) were located in the left colon. We conclude that, in this population, adenomas are common lesions that are frequently small. However, substantial proportions of these adenomas may be at risk for malignant degeneration due to the presence of villous architecture and higher grades of dysplasia. Because adenomas and hyperplastic polyps are endoscopically indistinguishable, all polyps found at endoscopy should be removed or ablated. PMID- 1858758 TI - Screening for colon malignancy with colonoscopy. AB - Screening of asymptomatic individuals for colon malignancy has been advocated for the past 20 yr in the hopes of reducing colon cancer mortality. Although sigmoidoscopy is an important element of current screening recommendations, the sensitivity of this test in asymptomatic subjects has never been studied. The purpose of this study was to determine the prevalence and location of polyps and cancers in an asymptomatic population by performing full colonoscopy. We wished to assess the sensitivity of screening flexible sigmoidoscopy to 60 cm by determining how many patients with adenomas or cancer had "index" adenomatous polyps in the distal 60 cm. One hundred five healthy male outpatients, over 50 yr old, with negative examinations for occult blood in stools and no prior history of colon pathology, had full colonoscopy. Careful examination of the distal 60 cm was performed, followed by a full colon examination to the cecum. Forty-three patients (41%) had adenomatous polyps, and only 19 of these patients had an index adenomatous polyp in the distal 60 cm. Therefore, the sensitivity of sigmoidoscopy was 44%. The prevalence of adenomas increased with age. Patients were assigned to one of three groups based on the findings in the distal 60 cm. Group 1 (n = 65) had no polyps in the distal 60 cm, but 18 of these patients (28%) had adenomatous polyps in the proximal colon. Among 21 patients with only hyperplastic polyps in the distal 60 cm (group 2), six patients (29%) had proximal adenomas. In group 3, eight of 19 patients (42%) with adenomas in the distal 60 cm also had proximal adenomatous polyps. We conclude that adenomatous polyps are common in asymptomatic men who have negative tests for fecal occult blood. Sigmoidoscopy to 60 cm had a sensitivity of only 44% in this patient population, suggesting that this is an insensitive test for the detection of patients with adenomatous polyps. PMID- 1858759 TI - Same-day upper and lower inpatient endoscopy: a trend for the future. AB - Performance of same-day upper and lower endoscopy has many potential advantages, as it may reduce costs, shorten hospital stay, and expedite patient care, but its feasibility, efficacy, and potential have not been carefully defined. We report here our experience with a group of 87 patients who underwent same-day upper and lower endoscopy (174 procedures) over a 2-yr period at a tertiary care VA Hospital, compared with an alternate-day upper and lower endoscopy group of 50 patients (100 procedures) over the same time period. Most patients were elderly males. Common indications for endoscopy were occult or overt gastrointestinal bleeding, previous or concomitant history of pertinent pathology (i.e., polyps, ulcers), abdominal pain, diarrhea, or other symptoms, abnormal radiological studies, and iron deficiency anemia. Both groups required similar amounts of intravenous sedation. There were no complications in either group. In both groups, common positive findings were inflammation (i.e., colitis, esophagitis), benign neoplasms, diverticulae, peptic ulcer, and cancer. In both groups, only 2 6% had negative upper and lower endoscopy, whereas either one procedure was negative in 25% and 18% of cases, respectively. We conclude that the practice of same-day inpatient upper and lower endoscopy is feasible, has excellent diagnostic yield, even in the elderly, and carries no increased risks. When indicated, the practice of same-day upper and lower endoscopy should be encouraged. PMID- 1858760 TI - Monitoring of blood pressure and heart rate during routine endoscopy: a prospective, randomized, controlled study. AB - Six hundred and eighteen patients were randomized to have automated cardiovascular monitoring or clinical observation during routine endoscopy. Hemodynamic parameters were recorded at 3-min intervals before, during, and after the procedure. Upper gastrointestinal endoscopy resulted in an increased heart rate (HR), while colonoscopy caused a decreased blood pressure (BP) and HR. Hemodynamic aberrations occurred in 71% of monitored patients, including hypotension 6%, hypertension 30%, bradycardia 26%, and tachycardia 32%. Only one third of the hypotensive episodes were recognized as aberrations, and therapeutic intervention did not improve outcome. No monitored or control patient had an adverse result. Certain hemodynamic changes were directly correlated with the baseline BP or HR and associated with the presence of coronary artery disease, particular medicines with cardiovascular effects and longer procedure duration. We conclude that automated monitoring during routine endoscopy unmasks frequent hemodynamic aberrations that are clinically insignificant. Routine monitoring during endoscopy does not improve outcome. PMID- 1858761 TI - Upper gastrointestinal lesions in elderly patients presenting for endoscopy: relevance of NSAID usage. AB - The occurrence of upper gastrointestinal disease and the relevance of nonsteroidal antiinflammatory drug (NSAID) usage were documented in 511 consecutive patients (321 women, 190 men) over 70 yr old, referred for upper gastrointestinal endoscopy in a district general hospital. The findings were benign esophageal disease (43%), normal (15%), gastric ulcer (11.5%), and duodenal ulcer (11%). Gastric ulcers were more common in women taking NSAIDs (25%) than in NSAID abstainers (7%) p less than 0.001 and male NSAID users (8%) p less than 0.001. Esophagitis and esophageal stricture were not influenced by NSAID usage, but gastric erosions were more common (10% vs. 3%) p less than 0.01. Of 142 patients receiving NSAIDs, 41% presented with hemorrhage, compared with 20.5% of NSAID abstainers (p less than 0.001). Hemorrhage was as common in aspirin takers (15 of 33, 45%) as in standard-dose NANSAID takers (43 of 109, 39%), even though 86% were taking 300 mg of aspirin per day or less. In elderly patients, esophageal disease is common. NSAID use, even low-dose aspirin, is associated with an increased risk of hemorrhage. In females, NSAID usage is associated with gastric ulcer. PMID- 1858762 TI - Prevalence of gastroesophageal reflux in elderly patients in a primary care setting. AB - Despite the aging of our population, there remains a paucity of information about gastroesophageal reflux (GER) in the elderly. To assess the prevalence and characteristics of GER within this patient population, questionnaires evaluating symptoms associated with GER were administered to 313 consecutive patients 62 yr old or older from a primary care setting. Fourteen percent of these patients reported having at least weekly heartburn. Ambulatory 24-h esophageal pH monitoring was accomplished in 54 of the 313 patients surveyed. Twenty percent (11/54) of this subgroup exhibited increased acid contact time (pH less than 4 for more than 6% of the monitoring period). Twenty-two percent (12/54) complained of heartburn, yet only six individuals (11%) exhibited both symptomatic and objective indications of acid reflux. Surprisingly, 31% (17/54) of the patients studied exhibited significant alkalinity within the distal esophagus (pH greater than 8 for greater than 1.5% of the monitoring period). Whereas 29% of these patients (5/17) reported heartburn, 40% of those reporting heartburn (2/5) had acid GER as well as excessive alkalinity. In contrast to patients with acid GER- none of whom reported pulmonary symptoms--24% (4/17) of these patients with esophageal alkalinity reported wheezing, nocturnal cough, or paroxysmal nocturnal dyspnea. Of the four patients with significant distal esophageal exposure to both acid and alkali, two reported heartburn and a third reported dysphagia. In addition to the somewhat higher prevalence of acid reflux than anticipated, a surprisingly high prevalence of esophageal alkalinity was observed. PMID- 1858763 TI - Five-day bismuth-free triple therapy for the eradication of Helicobacter pylori and reduction of duodenal ulcer relapse. AB - Previous studies have demonstrated that the eradication of Helicobacter pylori (H. pylori) is associated with a significant reduction of the rate of duodenal ulcer (DU) relapse. The aim of this study was to assess the long-term effect of a bismuth-free triple therapy on the eradication of H. pylori and reduction of DU relapse. After informed consent, 61 patients with endoscopically proven DU and H. pylori infection detected on 14C-urea breath test (BT) were included in the study. All patients received a combination of furazolidone, amoxicillin, and metronidazole, three times a day, for 5 days, in addition to eventual classical antiulcer agents prescribed by their attending physicians. BT was repeated after an interval of at least 60 days to evaluate H. pylori eradication. Endoscopy and another BT were performed again at 6.5 months after therapy to detect possible recurrences. Forty-eight patients completed the trial: 26 (54%) patients were negative for H. pylori at 6.5 months after the end of treatment, and 22 (46%) persisted H. pylori positive. Ninety-two percent of the patients in whom the bacteria were eradicated showed endoscopically healed ulcers and were asymptomatic, and two that were symptomatic presented only occasional pain not requiring therapy. Among the 22 patients who persisted H. pylori positive, six (27%) showed endoscopically active ulcers (p = 0.012) and eight (36%) patients continued to be symptomatic (p less than 0.01), and were still using antiulcer drugs (p = 0.002) 6.5 months after treatment. It is concluded that combined treatment with furazolidone, amoxicillin, and metronidazole for 5 days represents a well-tolerated, inexpensive, and effective therapeutic regime for the eradication of H. pylori and abolition of DU relapse in more than 50% of the patients during a follow-up period of 6.5 months. PMID- 1858764 TI - Diverticulitis of the duodenum: clinical and radiological manifestations of seven cases. AB - Seven patients with duodenal diverticulitis were evaluated by computed tomography (CT) and various other abdominal imaging techniques. The series included four men and three women who ranged in age from 47 to 84 yr (mean: 65 yr). They had presented with epigastric or periumbilical pain, low-grade fever, leukocytosis, and loss of appetite and weight due to postprandial cramps or vomiting. In each instance, the abdominal CT examination proved crucial in the diagnosis of duodenal diverticulitis, with contained perforation or inflammatory changes involving the adjacent structures. Five patients underwent laparotomy while two others were treated conservatively with antibiotics and/or percutaneous drainage of peridiverticular abscess. The clinical and radiological features of this uncommon entity are herein described, along with a brief review of the medical literature regarding the current approach to its diagnosis and management. PMID- 1858766 TI - Effect of clonidine on gallbladder contraction and small bowel transit time in insulin-treated diabetics. AB - Cholelithiasis is more prevalent in diabetics than in nondiabetics. Gallbladder dysmotility is supposed to be one of the causative factors. Reduced alpha adrenergic tone has been demonstrated in the enterocytes of diabetic rats, and its correction by clonidine might explain the beneficial effect that the drug has on diabetic diarrhea. We therefore surmised that diabetic cholecystoparesis could also be due to alpha-adrenergic alterations. To test this hypothesis, we studied gallbladder contractions by real time ultrasonography, and small bowel transit time by lactulose hydrogen breath test, in 13 insulin-requiring diabetics before and after administration of the alpha-adrenergic stimulant clonidine (0.3 mg orally). That plasma levels were sufficient was evidenced indirectly by a fall in blood pressure. Clonidine significantly improved the rate of emptying (0.0193 +/- 0.00057/min vs. 0.0318 +/- 0.0027/min; p less than 0.005), but not the fasting and residual gallbladder volumes. Small bowel transit time was significantly prolonged after clonidine (169 +/- 17 min vs. 208 +/- 17; p less than 0.05). These results suggest that 1) reduced alpha-adrenergic tone corrected by clonidine may be present in the diabetic gallbladder, and 2) clonidine's antidiarrheal effect might be explained, at least in part, by a prolongation of the small bowel transit time. PMID- 1858765 TI - Alpha 1-antitrypsin clearance as an aid in the management of patients with celiac disease. AB - One hundred and thirty-two different intestinal alpha 1-antitrypsin clearance tests were performed in 48 untreated adult celiac patients, 64 patients taking a gluten-free diet, and 20 adult healthy controls. In the untreated group, 95% of patients had enteric protein loss with values higher than the upper limit of normality (mean +/- 2 SD). In the treated group of patients, only 22% had abnormal levels of alpha 1-antitrypsin clearance. Sixteen patients who had elevated clearance before treatment had decreased clearance after an average of 7.4 months on a gluten-free diet. There was a significant relation (p less than 0.05) between the alpha 1-antitrypsin clearance and the degree of alteration of the jejunal histological structure. We conclude that enteric protein loss is a very frequent finding in celiac patients and the measurement of alpha 1 antitrypsin clearance may be a reliable method to evaluate the activity of the disease and useful in following the efficacy of treatment. PMID- 1858767 TI - Plasma level of tumor necrosis factor in disseminated intravascular coagulation. AB - The plasma level of tumor necrosis factor (TNF) was determined in 20 normal individuals, 52 patients with disseminated intravascular coagulation (DIC), 22 pre-DIC patients, and 39 non-DIC patients. TNF was not detected in the normal subjects, and the level was very low in non-DIC patients. However, the TNF level was significantly elevated in DIC patients, and it was moderately increased in pre-DIC patients shortly before the onset of DIC. This increase in circulating TNF may be associated with DIC. TNF was higher in DIC associated with solid cancer than in DIC associated with leukemia or sepsis. The increase in plasma TNF level was mildly correlated with DIC score, and it was significantly increased in patients with poor prognosis. However, the plasma TNF level in DIC patients with organ failure was not significantly different from those without organ failure. We conclude that the increase in circulating TNF reflects the pathogenic factors in DIC rather than being a consequence of organ failure due to DIC. PMID- 1858768 TI - Plasma adenosine deaminase2 is a marker for human immunodeficiency virus-1 seroconversion. AB - Plasma adenosine deaminase2 (ADA2) has recently been proposed to be a marker for human immunodeficiency virus-1 (HIV) infection. We measured ADA2 levels in plasma from two groups of white homosexual males at 6-month intervals for a total of 2.5 years. One group consisted of 6 subjects who seroconverted for HIV, and the other consisted of 8 HIV seropositive patients who progressed from asymptomatic (CDC Groups II/III) to symptomatic (CDC Group IV) disease. Seroconversion was associated with a significant increase in plasma ADA2 which persisted throughout follow-up of 1.5 years. However, disease progression in HIV seropositive patients was not associated with any significant change in plasma ADA2. In conclusion, ADA2 may represent a unique marker for HIV seroconversion which does not change with later progression to symptomatic disease. PMID- 1858769 TI - Transient erythroblastopenia in the first year of life. AB - The distinction between transient erythroblastopenia of childhood (TEC) and congenital red cell aplasia (Blackfan-Diamond anemia) is usually possible at presentation using clinical and laboratory data. When hypoplastic anemia occurs in the first year of life, however, the distinction is more difficult. We describe 7 infants with hypoplastic anemia who illustrate this diagnostic dilemma. PMID- 1858770 TI - On the temporal development of erythrocyte sedimentation rate using sealed vacuum tubes. AB - The temporal development of the erythrocyte sedimentation rate (ESR) was studied in wide, short vacuum tubes. It was found that in about 3% of the specimens arriving in the laboratory the ESR developed in three different phases during 60 min, whereas the other showed only two. The specimens with three phases behaved similarly in the Westergren method. It was shown that the Westergren ESR can be estimated with an acceptable accuracy already from measurements obtained after 30 min. Reproducibility and precision were improved by using a special instrument. Several advantages by this procedure were recognized, e.g., quicker results, identification of several otherwise missed rapid ESR. Accurate timing of the readings further improves accuracy and precision, and permits estimation of ESR (Westergren) up to 100 mm. In view of the obvious phases in the development of the ESR, it is proposed that this abbreviation is interpreted as erythrocyte sedimentation reaction and that the kind of quantity that is length is expressed in mm. PMID- 1858771 TI - Computed tomography for diagnosis of hepatic rupture in primary systemic amyloidosis. AB - Hepatic rupture in primary systemic amyloidosis is extremely ominous; death occurs in hours to days. We present two cases of hepatic rupture diagnosed ante mortem with computed tomography (CT). Surgical repair was possible in one instance and successfully controlled the bleeding. In the setting of primary amyloidosis, the early use of CT scanning for undiagnosed ascites, hypotension, or rapid organ enlargement may lead to early diagnosis and potential surgical correction. PMID- 1858772 TI - Warfarin skin necrosis: recurrence in the absence of anticoagulant therapy. AB - Skin necrosis is a well-known yet rare complication of oral anticoagulant therapy. We report the unusual recurrence of lesions typical of warfarin skin necrosis in the absence of anticoagulant therapy. A 59-year-old woman developed skin necrosis while receiving prophylactic warfarin following the detection of a large left ventricular thrombus. The warfarin was discontinued and the lesions improved. One month later new areas of skin necrosis developed although the patient had received no further warfarin. Progressive congestive heart failure, poor nutrition, and prolonged oral antibiotic therapy preceded the recurrence. Vitamin K deficiency was present on admission. The potential role of vitamin K dependent coagulation factors in the pathogenesis of anticoagulant-associated skin necrosis is discussed. PMID- 1858773 TI - Spinal cord compression secondary to extramedullary hematopoiesis: a noninvasive management based on MRI. AB - We report the first case of spinal cord compression secondary to extramedullary hematopoiesis in which the diagnosis was made by magnetic resonance imaging (MRI). Based on the great advantage of this imaging test that visualizes the entire spine, the noninvasive approach to such patients, using low-dose radiation therapy and guided by MRI is discussed. This management appears to be both efficacious and safe. PMID- 1858774 TI - Retroperitoneal fibrosis accompanying immune thrombocytopenia. AB - Retroperitoneal fibrosis represents an idiopathic systemic fibrosing syndrome which leads to the development of progressive hydronephrosis and azotemia (Stewart and Friberg: Southern Medical Journal 77:1185-1187, 1984; Morad et al.: American Journal of Medicine 82:363-366, 1987). Evidence in the literature supports a hypothesis that retroperitoneal fibrosis represents a systemic autoimmune process (Lichon et al.: Journal of Rheumatology 11:373, 374, 1984; Lipman et al.: JAMA 196:204-206, 1966; Littlejohn and Keystone: Journal of Rheumatology 8:665-669, 1981; Katz et al.: American Journal of Clinical Pathology 67:436-439, 1977). We report a case of a patient with retroperitoneal fibrosis, immune thrombocytopenia, presence of antinuclear antibody, and direct Coombs positivity which provides further evidence that retroperitoneal fibrosis is an autoimmune process. Progressive obstructive uropathy related to his fibrosis led to bilateral hydronephrosis and significant renal function impairment. Also, he developed marked immune thrombocytopenia. Treatment with prednisone produced a dramatic response in both platelet count and renal function. PMID- 1858775 TI - Preliminary report on the use of desferrioxamine in the treatment of Plasmodium falciparum malaria. AB - The administration of 0.5 g (IM) of desferrioxamine every 12 hr for 3 days with 25 mg/kg (total dose for three days) of chloroquine abated the parasitemia of Plasmodium falciparum infected individuals more rapidly than chloroquine alone. Two patients with in vitro evidence of total or partial resistance to chloroquine also were successfully treated with the combination of drugs, and were free of parasitized red cells by day 7. Further clinical trials and development of desferrioxamine in the treatment of P. falciparum are warranted. PMID- 1858777 TI - Ph-positive chronic myelogenous leukemia evolving after polycythemia vera. PMID- 1858776 TI - Platelet aggregation in hyperapobetalipoproteinemia. AB - Hyperapobetalipoproteinemia (HyperapoB) is a lipid disorder characterized by premature coronary disease, although the mechanisms have not been elucidated. Because abnormalities in platelet function may represent an enhanced susceptibility to coronary thrombosis, the aggregability of platelets was examined in hyperapoB subjects. Compared to controls, there were no significant differences in either platelet lipid composition or in aggregation to epinephrine, ADP, or collagen. In contrast to other dyslipidemias, platelet function does not appear to be abnormal in this well defined lipid disorder. PMID- 1858779 TI - Would "bull's eye cell" be a better morphological description than "target cell"? PMID- 1858778 TI - Abnormal megakaryocytes in thrombocytopenia associated with HIV-1 infection. PMID- 1858780 TI - Agranulocytosis caused by ticlopidine and its mechanism. AB - A 75-year-old female patient with agranulocytosis caused by ticlopidine is reported. She took the drug at 200 mg/day for 30 days to prevent recurrence of cerebral infarction. The leukocyte count at the nadir was 500/microliters on the 34th day since she started to take the drug. Complete recovery of her peripheral leukocytes came 12 days after its withdrawal. In this patient, mechanisms of ticlopidine-caused agranulocytosis were studied. The lymphocyte stimulation test using ticlopidine was negative. In the culture of marrow cells depleted of lymphocytes, ticlopidine directly inhibited the CFU-C in a dose-dependent manner. Neither the serum on the day of admission nor the T-lymphocytes pre-cultured with ticlopidine had any effect on the CFU-C. The lymphocyte stimulation test is useless in an attempt to find the causal drug in agranulocytosis if it is caused in a directly toxic manner. Agranulocytosis caused by ticlopidine is rare, but careful follow-up is necessary in the case of patients on the drug because there are some whose marrow cells are very sensitive to it. PMID- 1858781 TI - Expression of transferrin receptors on monocytes in hemochromatosis. AB - To assess whether an abnormality in transferrin receptor expression or regulation could represent an underlying metabolic defect in the reticuloendothelial (RE) system in hemochromatosis, monocytes were analyzed for the expression of the transferrin receptor using a monoclonal antibody (Act II) to the transferrin receptor (CD71) and flow cytometric analysis. Hemochromatosis patients (n = 14), and normal volunteers with no clinical evidence of iron overload (n = 14) were studied. A significant inverse relationship was observed for the relationship between the expression of transferrin receptor on monocytes and log(hepatic iron concentration) in hemochromatosis patients (r = -0.59, P less than .02) and also for the relationship between the expression of transferrin receptor and log(serum ferritin) in normal volunteers (r = -0.90, P less than .001). There was no significant difference in the mean expression of monocyte transferrin receptor between hemochromatosis patients and normal volunteers. However, the expression of the transferrin receptor in hemochromatosis patients was disproportionately higher than would be predicted from the relationship between serum ferritin and transferrin receptor expression in normal volunteers. The inverse relationship of the monocyte transferrin receptor relative to body iron stores in hemochromatosis is consistent with observations in other tissues, and suggests that non transferrin iron metabolism, including ferritin, requires further investigation in the RE cell in hemochromatosis. PMID- 1858782 TI - Therapeutic implications and sites of relapse predicted by elevated posttherapy erythrocyte sedimentation rate in early stage Hodgkin disease. AB - An analysis was performed of all 57 early relapses (ER) (within 18 months of therapy initiation) seen in a group of 301 patients treated on three successive European Organization for Research and Treatment of Cancer (EORTC) protocols from 1964 to 1981; to determine whether a posttherapy elevated erythrocyte sedimentation rate (ESR) (greater than or equal to 30 mm) could predict the type of relapse and the effect upon the relapse of different therapies received. Overall most ER occurred in extranodal (EN) (42%) or irradiated transdiaphragmatic nodal (TDN) (40%) sites. Compared to patients with normal posttherapy ESR (n = 12), patients with elevated posttherapy ESR (n = 45) had the same proportions of outfield and late relapses; more frequent multiple sites of ER (38% vs. 25%), increased proportions of early EN relapses (16% vs. 3%), TDN relapses (17% vs. 2%), and other ER (6% vs. 1%). ER were most frequently observed between 1964 and 1971, and "modern" radiotherapy (Rt) decreased ER overall from 27% to 13% and for elevated posttherapy ESR patients from 54% to 25%. When chemotherapy (Ct) was used as either adjuvant or initial therapy, ER were greatly reduced vs. Rt alone [overall (6% vs. 28%) and for patients with elevated posttherapy ESR (10% vs. 39%)]. Stepwise logistic regression showed Ct to be the most important factor "protecting" from EN relapse, but elevated posttherapy ESR was still significant. For early TDN relapse, elevated posttherapy ESR had the highest predictive value for relapse, greater than the types of radiation fields used and chemotherapy. An unexplained elevated posttherapy ESR, regardless of previous therapy, predicts for ER from aggressive HD, frequently in EN and irradiated areas, and warrants further early therapy. PMID- 1858783 TI - Suppressed natural killer cell activity in patients with chronic autoimmune thrombocytopenic purpura. AB - Natural killer (NK) cell activity was studied in 17 patients with primary chronic idiopathic autoimmune thrombocytopenic purpura (ATP). Fifteen of 17 patients had a significantly reduced NK cytotoxicity against 51chromium labeled K562 target cells (mean LU20% = 18 +/- 20 in patients versus 65 +/- 25 in controls, P less than 0.001). NK activity was also significantly reduced in all of six patients with secondary ATP as compared with normal controls (LU20% 28 +/- 15, respectively, P less than 0.005). The NK activity in both patient groups correlated with the duration of therapy being received (r = 0.60, P less than 0.001). Immunophenotypic analysis of peripheral blood mononuclear cells from patients with ATP revealed that CD8- cells bearing CD57 (HNK-1, Leu 7) and CD3- cells bearing CD56 (Leu 19) were quantitatively within the normal range. These findings indicate that patients with ATP have a functional defect in NK cytolytic activity. PMID- 1858785 TI - Granulocyte-macrophage colony stimulating factor for the treatment of drug induced agranulocytosis. AB - Drug induced agranulocytosis is an uncommon but potentially fatal complication. In some cases, it may be associated with hypoplasia and depletion of granulocytic precursors in the marrow, leading to prolonged neutropenia. We report on the use of granulocytic-macrophage colony stimulating factor (GM-CSF) in two such cases, at a dose of 10 micrograms per kilogram per day subcutaneously. The absolute neutrophil count rose above 500/mm3 in 3 days in both cases. We believe that GM CSF expedited the recovery of granulocyte counts in our patients and warrants further study in the management of drug induced neutropenia. PMID- 1858784 TI - The respiratory burst oxidase and the molecular basis of chronic granulomatous disease. PMID- 1858786 TI - Isolated relapse of acute myelogenous leukemia presenting as a gastric ulcer. AB - Isolated gastrointestinal (GI) infiltrate is unusual at presentation or relapse of acute myelogenous leukemia (AML). We report a case of acute myelogenous leukemia (FAB-M4) whose isolated relapse presented as a bleeding gastric ulcer. The patient was a 30-year-old male who had been diagnosed to have AML in June 1988. While in third complete remission, he underwent a sibling allogeneic HLA matched bone marrow transplant. Five months after transplantation, he was readmitted for pneumonia. While in the hospital, he had an episode of upper GI bleeding. The endoscopy revealed a leukemic gastric ulcer, with morphology and immunophenotyping identical to his initial AML. There was no evidence of leukemia in the blood or bone marrow. Although different types of leukemic infiltrates have been recognized at post-mortem examination, our case is unique because AML presenting as an isolated malignant ulcer has not been described previously. We conclude that relapsing AML may present as an isolated gastric ulcer and suggest that any suspicious lesion on upper GI endoscopy should be biopsied after aggressive platelet support. PMID- 1858787 TI - Flow cytometric analysis of anti-platelet antibodies in patients with chronic idiopathic thrombocytopenic purpura (ITP) using acid-treated, formalin-fixed platelets. AB - Acid treatment of normal washed platelets prepared by albumin density gradient centrifugation followed by formalin fixation effectively eliminates HLA class I antigens from the platelet surface, without altering the immunoreactivity of platelet membrane glycoproteins Ib and IIb/IIIa complex. Using these platelets, flow cytometric analysis was performed on a total of 20 sera from different patients with chronic ITP, and revealed an inverse linear correlation between the platelet count and the mean fluorescence intensity which represents a relative amount of platelet-bound IgG. These results suggest that acid-treated, formalin fixed platelets can be used as specimens to detect anti-platelet antibodies to differentiate from those to HLA-class I antigens. PMID- 1858788 TI - Usefulness of electron microscopy in the diagnosis of congenital dyserythropoietic anemia type I: report of a case. AB - This report describes a case of congenital dyserythropoietic anemia (CDA) type I diagnosed in a 22-year-old woman with a two year history of macrocytic anemia. Light microscopy study of bone marrow disclosed only minor and nonspecific findings, without erythroid hyperplasia. Electron microscopy of bone marrow erythroblasts surprisingly showed most of the classical features of CDA type I. Electron microscopy may be an important tool for the diagnosis of macrocytic anemia of obscure origin, especially in young patients. PMID- 1858789 TI - Stability of peripheral hematological parameters after chronic acetylcholinesterase inhibition in man. AB - Acetylcholinesterase (AChE; EC 3.1.1.7) is present in both primitive and mature erythroid cells, and a role has been suggested for the enzyme in regulation of differentiation in the human erythron. AChE is also a major enzyme in the central nervous system; alteration of its activity has been proposed as a therapeutic strategy in Alzheimer disease. We recently treated 18 Alzheimer disease patients with metrifonate, a long-acting AChE inhibitor, over periods up to 7 months, with resulting erythrocyte AChE inhibition as high as 82 per cent of baseline values. Despite chronic reduction of enzyme activity, no significant alterations were noted in erythrocyte, leukocyte or platelet characteristics or numbers that would suggest a deleterious effect of AChE inhibition on normal differentiation. Thus, any modification of developmental pathways appears to be compensated by other regulatory mechanisms in the intact organism. PMID- 1858790 TI - Paraprotein index: a simple prognostic parameter for multiple myeloma. PMID- 1858791 TI - Leukemic pneumonitis in monocytic crisis of chronic myelogenous leukemia. PMID- 1858792 TI - Anomalous anticardiolipin antibody results may be due to cofactor variability. PMID- 1858793 TI - Satisfaction of physicians and nurses with clinical pharmacy services. PMID- 1858795 TI - Expressing the mission of pharmacy practice. PMID- 1858794 TI - H2-receptor antagonists and acute intermittent porphyria. PMID- 1858796 TI - Counseling patients about drug use. PMID- 1858797 TI - Use of cytogenetic methods to determine mutagenic changes in the blood of pharmacy personnel and nurses who handle cytotoxic agents. AB - Lymphocytes of subjects from throughout the United Kingdom were studied over a two-year period beginning in January 1985 to determine the level of chromosomal damage produced by environmental exposure to cytotoxic agents. A small pilot study was conducted to determine the expected background level of chromosomal aberrations. Four groups of subjects were then recruited: pharmacy personnel who reconstituted the drugs under recommended conditions, nurses who did not reconstitute the drugs but worked on units where patients received cytotoxic chemotherapy, unexposed office workers from the same geographic location as the pharmacy personnel and nurses (negative control), and patients receiving cytotoxic drugs (positive control). Subjects completed questionnaires about smoking, viral illnesses, radiation exposure, and medication use in the past 12 months; pharmacy personnel were asked the numbers of times (1) they had handled specific drugs and (2) spills had occurred with these drugs. Lymphocytes from subjects were incubated for 48 hours, and first-division metaphases were examined for chromosome and chromatid aberrations; damage was measured as the number of aberrations per 100 cells. For a blood sample to be included in the analysis, at least 100 metaphase divisions had to be examined. Data were analyzed for 50 pharmacy staff members, 11 nurses, 12 controls, and 6 patients. Metaphase divisions in cells of the pharmacy personnel and nurses indicated no significant difference in chromosomal damage compared with the unexposed office workers. When the pharmacy, nurse, and control groups were pooled into a nonpatient group and compared with the patient group, significantly greater damage was observed in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858798 TI - Extemporaneous compounding activities and the associated informational needs of pharmacists. AB - The results of an ASHP survey of extemporaneous compounding activities and the associated informational needs of selected pharmacists are reported. A questionnaire on extemporaneous drug formulations was mailed in September 1989 to 517 pharmacists with presumed interest in or knowledge of extemporaneous compounding activities. There were 235 questionnaires returned by recipients, for a net response rate of 45.6%. Of these 235 questionnaires, 210 were usable for the analyses. Eighty percent of the respondents practiced in hospitals. The respondents listed 314 single-entity and combination drug formulations that are frequently compounded in their institutions but for which adequate information on stability was judged not to be available. Oral suspensions were the most commonly listed dosage forms for which stability information was deemed to be needed. Other frequently reported informational needs pertained to the preparation of topical and ophthalmic drug formulations and pediatric dilutions. Data on the patient age groups involved, the usual routes of administration, and the approximate total volume and dose (volume) per patient were also reported for each drug formulation. Pharmacists perform a broad range of extemporaneous compounding activities, and further efforts are needed to supply practitioners with pertinent information on extemporaneous drug formulations. PMID- 1858799 TI - Multidimensional work sampling to study the activities of decentralized clinical pharmacists. AB - Self-reported multidimensional work sampling (MDWS) was used to study the activities of decentralized clinical pharmacists at six hospitals in Portland, Oregon, and Seattle-Tacoma, Washington, in March through June 1989. A community hospital, a university hospital, and a hospital associated with a health maintenance association were selected in each city, and pharmacists at each site who provided clinical services were recruited. Each pharmacist wore a random reminder device and recorded the activity during which the device sounded by writing on a card numbers assigned to describe work activity, contact, location, and function. Of 6609 classifiable observations, 34.5% (2280) were of clinical activities and 35.8% distributive activities. Pharmacists spent 28.6% of their clinical time reviewing and assessing patients' charts, 17.1% on clinical rounds, 15.9% on activities related to therapeutic drug monitoring, 10.2% providing drug information, 11.6% attending or giving formal education, 6.1% doing research, and 2.6% attending meetings. The average pharmacist spent less than 10 minutes each day with patients but spent a substantial portion of time providing clinical services to other health professionals. Self-reported, multidimensional work sampling appears to be a valuable method for describing and monitoring decentralized pharmacists' work activities at multiple sites and work settings. PMID- 1858801 TI - Attitudes of Ohio hospital pharmacists toward pharmacy technicians. AB - A survey was conducted to determine the attitudes of Ohio pharmacists toward pharmacy technicians. A questionnaire was developed with questions about the current and future scope of technician responsibilities; training, certification and licensure; and possible displacement of pharmacist positions. The questionnaire was mailed in January 1990 to a random sample of 357 hospital pharmacists registered with the Ohio State Board of Pharmacy. There were 182 usable questionnaires returned, for a response rate of 51%. Nearly all the respondents (98.4%) employed pharmacy technicians. Of 32 functions listed in the questionnaire, 16 were performed by technicians at more than half of the responding hospitals. The functions performed by technicians varied depending on the size and location of the hospital; and the education, experience, and current position of respondents influenced their opinions on the appropriateness of having technicians perform several functions now and in the future. Most respondents agreed that all technicians should receive standardized training and education, and more than a third believed that technicians should be certified. The respondents did not believe that increased use of technicians would eliminate present pharmacist positions in their department but were neutral toward a statement that technicians would eliminate pharmacist positions in general. Ohio pharmacists' attitudes toward the expanding role of pharmacy technicians seemed in concert with the recommendations that have emerged in the profession. PMID- 1858800 TI - Use of antimicrobial drugs in adults before and after removal of a restriction policy. AB - The effects on the quantity and quality of antimicrobial drug use of removing an antimicrobial restriction policy are reported. Monthly totals for the number of courses of antimicrobial therapy and expenditures based on grams used were obtained from pharmacy records on adult inpatients for a portion (July-December 1987) of the restriction policy term and for the six months (July-December 1988) immediately after the policy ended. Data were obtained for nine restricted drugs and for three that were never restricted. Retrospective drug-use reviews were conducted for ceftazidime and imipenem-cilastatin. For the restricted agents, the total number of courses of therapy increased by 158% after the restriction policy was removed, and total expenditures increased by 103%. There were no significant changes in the number of courses of therapy or cost for the unrestricted antimicrobials. In the postrestriction period, ceftazidime and imipenem cilastatin were used more often in patients who were less critically ill. Inappropriate use of imipenem-cilastatin occurred significantly more often after the restrictions were removed. Other factors potentially affecting the use of antimicrobials, such as patient age and the incidence of nosocomial infections, did not differ substantially between the two periods. The removal of an antimicrobial restriction policy resulted in increased use of and higher expenditures for previously restricted agents, as well as an increase in the inappropriate use of at least one agent. PMID- 1858802 TI - Stability of dobutamine hydrochloride in peritoneal dialysis solutions. AB - The stability of dobutamine hydrochloride in peritoneal dialysis solutions at 4, 26, and 37 degrees C was determined. Dobutamine (as the hydrochloride salt) was added to dialysis solutions containing 1.5% or 4.25% dextrose to concentrations of 2.5, 5.0, and 7.5 mg/mL. Samples were stored at 4, 26, and 37 degrees C to mimic refrigerator, room, and body temperature, respectively. At 0, 4, 8, and 24 hours, the samples were analyzed in triplicate by stability-indicating high performance liquid chromatography to determine the percentage of drug remaining. More than 90% of the drug was retained under all storage conditions in 1.5% dextrose dialysate containing an initial dobutamine hydrochloride concentration of 5.0 or 7.5 micrograms/mL. The mean concentration in the samples containing an initial dobutamine hydrochloride concentration of 2.5 micrograms/mL and stored at room temperature remained greater than 90% of the initial concentration for the first four hours and then decreased to less than 90%. Dobutamine was stable in 4.25% dextrose dialysate regardless of the initial concentration or the storage condition. Dobutamine hydrochloride 5.0 and 7.5 micrograms/mL in 4.25% dextrose dialysis solution was stable under all the test conditions. Dobutamine hydrochloride 2.5 micrograms/mL was stable in 1.5% dextrose dialysate for only four hours at room temperature. PMID- 1858803 TI - Stability and compatibility of methylprednisolone sodium succinate and cimetidine hydrochloride in 5% dextrose injection. AB - The stability and compatibility of methylprednisolone sodium succinate in admixtures with cimetidine hydrochloride in 5% dextrose injection were determined. Admixtures containing methylprednisolone sodium succinate, in concentrations equivalent to methylprednisolone 0.4 or 1.25 mg/mL, and cimetidine 3 mg/mL (as the hydrochloride salt) were prepared in 5% dextrose injection 100 mL. Control solutions containing each drug alone at the same concentrations were also prepared. The admixtures were prepared in triplicate and were kept in polyvinyl chloride infusion containers at controlled room temperature (24 degrees C). Immediately after mixing and at 2, 4, 8, 12, and 24 hours, samples were removed and visually inspected, measured for pH, and assayed by stability indicating high-performance liquid chromatography to determine the concentrations of methylprednisolone 21-succinate ester and cimetidine. No visual evidence of incompatibility was noted either with the unaided eye or a microscope. No substantial changes in pH occurred over the study period. The addition of cimetidine decreased the pH of the methylprednisolone sodium succinate control solutions from about 7.3 to about 5.6. The concentrations of methylprednisolone 21-succinate ester and cimetidine in both test and control solutions did not change significantly over the 24-hour study period. Methylprednisolone sodium succinate, in concentrations equivalent to methylprednisolone 0.4 and 1.25 mg/mL, was chemically stable and visually compatible in admixtures with cimetidine 3 mg/mL (as the hydrochloride salt) in 5% dextrose injection 100 mL at 24 degrees C for 24 hours. PMID- 1858804 TI - Stability of acetazolamide in suspension compounded from tablets. AB - The stability of acetazolamide in an extemporaneous suspension compounded from tablets was studied. Acetazolamide 25-mg/mL suspension was prepared by levigating the comminuted 250-mg tablets with 70% sorbitol solution. The mixture was incorporated into a suspension vehicle containing magnesium aluminum silicate and carboxymethylcellulose sodium. Appropriate sweeteners, flavoring agents, preservatives, humectants, and pH adjusters were then added. The suspension was stored in amber glass bottles at 5, 22, 30, 40, and 50 degrees C. Samples were analyzed for the concentration of acetazolamide by stability-indicating high performance liquid chromatography on days 3, 7, 11, 18, 24, 32, 42, 54, and 79. For batches stored at 5, 22, and 30 degrees C, the initial acetazolamide concentration was maintained during the entire 79 days of the study. However, the concentrations in the batches stored at 40 and 50 degrees C were below 90% of the initial value after 79 and 32 days, respectively. The Arrhenius plot was used to predict a shelf life of the suspension at room temperature of 371 days. Acetazolamide oral suspension 25 mg/mL was stable for at least 79 days at 5, 22, and 30 degrees C. The formulation should be maintained at pH 4-5 and stored in amber glass bottles. PMID- 1858806 TI - Outcome-focused patient-care standards developed by a local society of hospital pharmacists. PMID- 1858807 TI - Time requirements associated with three pharmacy inventory-control methods. PMID- 1858805 TI - Stability of methadone in four vehicles for oral administration. AB - The stability of methadone in vehicles commonly used for oral administration was determined. Solutions of methadone were prepared in (1) orange-flavored Tang, (2) grape-flavored Kool-Aid, (3) apple juice, (4) grape-flavored Crystal Light, and (5) grape-flavored Crystal Light plus 0.1% sodium benzoate. For each of the first four preparations listed, two solutions were formulated at each methadone hydrochloride concentration of 0.2, 0.8, and 1.5 mg/mL; one set of three concentrations of each solution was stored in a refrigerator at 5 degrees C for up to 55 days, and the other set was stored unprotected from light at 20-25 degrees C for up to 17 days. Only three Crystal Light plus sodium benzoate solutions were prepared at the same methadone concentrations and stored at 20-25 degrees C for up to 29 days. Methadone concentrations were measured by high performance liquid chromatography. Methadone was stable (loss of potency, less than 5%) for up to 17, 11, 9, and 8 days when stored at 20-25 degrees C in Kool Aid, Tang, apple juice, and Crystal Light, respectively, and for up to 29 days when stored at 20-25 degrees C in Crystal Light plus sodium benzoate. Methadone was stable for up to 55, 49, 47, and 34 days when stored at 5 degrees C in Kool Aid, Tang, apple juice, and Crystal Light, respectively. All the solutions that did not contain sodium benzoate and were stored at room temperature displayed unacceptable microbial growth after approximately two weeks. No significant loss of methadone potency occurred in any of the vehicles for oral administration during the study. PMID- 1858808 TI - A nontraditional approach to internship programs. PMID- 1858809 TI - Computer system for determining trends in controlled-substance discrepancies. PMID- 1858810 TI - Stability of oxybutynin chloride syrup after repackaging in unit doses. PMID- 1858811 TI - Physical stability of repackaged enteric-coated magnesium chloride tablets. PMID- 1858812 TI - Stability of antipyrine plus caffeine in intravenous solution. PMID- 1858814 TI - Executive summary of petition requesting recognition of psychopharmacy. Task Force on Specialty Recognition of Psychopharmacy Practice. PMID- 1858813 TI - Women of childbearing capacity may not be excluded from working with hazardous substances because of their gender. PMID- 1858815 TI - Safe use of benzodiazepines and other drugs: the pharmacist's duty to counsel. PMID- 1858816 TI - Ten years' experience with AIDS: current status and future prospects. PMID- 1858818 TI - Free T3 toxicosis: a distinct entity? PMID- 1858817 TI - Monitoring L-thyroxine therapy: lessons from the effects of L-thyroxine on bone density. PMID- 1858819 TI - Poor tolerance of zidovudine in an HIV-asymptomatic patient with alpha thalassemia. PMID- 1858820 TI - Tranexamic acid in the treatment of hereditary angioedema. PMID- 1858821 TI - Etiology of chest pain in mitral valve prolapse. PMID- 1858822 TI - Staphylococcus aureus Hickman catheter infections. PMID- 1858823 TI - ACE inhibitor-induced hypoglycemia. PMID- 1858824 TI - Helicobacter pylori-negative duodenal ulcer. AB - PURPOSE PATIENTS AND METHODS: Helicobacter pylori (HP) is present in more than 90% of duodenal ulcers (DUs). To investigate the pathophysiology in those patients with DU who are HP-negative compared with those who are HP-positive, we interviewed consecutive patients prior to endoscopy regarding factors often associated with ulcer disease. At esophagogastroduodenoscopy, antral biopsy specimens were obtained for urease test, culture, and Warthin Starry staining for HP in all patients with DU who did not have active bleeding. RESULTS: Compared with HP-positive patients who had DU, HP-negative patients with DU were more likely to be aspirin users and less likely to have had prior ulcers. HP-positive patients with DU had more severe antral inflammation than HP-negative patients. Whites were more likely to be HP-negative than blacks. HP-negative patients with DU most commonly presented with bleeding, whereas HP-positive patients with DU presented with pain. CONCLUSIONS: Our findings suggest a different mechanism for DUs in patients who are HP-positive versus those who are HP-negative, and this difference might have a bearing on treatment. The absence of HP should lead to a more thorough search for nonsteroidal anti-inflammatory drug/aspirin use, Zollinger-Ellison syndrome, and other potential causes of DUs. PMID- 1858825 TI - Radiographically occult endobronchial obstruction in bronchogenic carcinoma. AB - PURPOSE: While central endobronchial tumors may become radiographically detectable when they cause significant endobronchial obstruction, the incidence of radiographically undetectable obstruction is not known. This study prospectively examined the incidence of radiographically undetectable completely obstructing lesions encountered during routine diagnostic bronchoscopy. PATIENTS AND METHODS: Patients referred for bronchoscopy at the San Diego Veterans Administration Medical Center because of suspected bronchogenic carcinoma formed the population base. Chest radiographs were interpreted routinely 24 hours prior to bronchoscopy. Patients found to have complete endobronchial obstruction during bronchoscopy were included in the analysis. RESULTS: Eighty-one completely obstructing lesions were found in 77 patients. No radiographic signs of obstruction were found in 36 (44%) completely obstructing endobronchial lesions. There was no difference in the rate of radiographically occult tumors based on cell type. Obstruction of segmental bronchi was more likely to be undetectable than obstruction of more proximal airways. Chest radiographs were normal in 13 (16%). All 13 had risk factors for and symptoms suggestive of bronchogenic carcinoma. CONCLUSION: Complete endobronchial obstruction due to bronchogenic carcinoma can occur frequently in patients at risk for lung cancer. The significant incidence of radiographically undetectable complete obstruction has implications for the diagnosis, staging, and assessment of treatment of lung cancer. PMID- 1858826 TI - Malaria in travelers in Rhode Island: a review of 26 cases. AB - PURPOSE: We reviewed our experience with malaria in two community hospitals in Rhode Island from 1986 to 1990. RESULTS: Twenty-six patients with malaria were identified. Fifteen patients were immigrants who had acquired malaria while visiting their country of origin, particularly West Africa. Fever was present in 67% of cases and gastrointestinal complaints were prominent in 26%. Individuals with a past history of malaria could accurately distinguish current malarial infections from other febrile illnesses. Two patients developed cerebral malaria. Plasmodium falciparum was identified in 77% of the cases. CONCLUSIONS: Malaria is an important diagnosis that United States physicians must consider in the medical evaluation of returning travelers. A significant increase in the number of cases of P. falciparum acquired in East Africa has been reported in recent years. P. falciparum infection must be rapidly diagnosed and treated since delays may result in complications of malaria that may lead to death. Mefloquine is currently recommended by the Centers for Disease Control for prevention of malaria in travelers visiting countries endemic for chloroquine-resistant malaria. This change may alter the epidemiology of malaria in the United States in the future. PMID- 1858827 TI - Activation of the host response in human Plasmodium falciparum malaria: relation of parasitemia to tumor necrosis factor/cachectin, thrombin-antithrombin III, and protein C levels. AB - PURPOSE: Hemostatic alterations and elevated tumor necrosis factor/cachectin (TNF alpha) serum levels may contribute to the pathogenesis of organ complications in human Plasmodium falciparum malaria. Therefore, we examined whether altered protein C (PC) and thrombin-antithrombin III (TAT) plasma levels correlated with TNF alpha serum concentrations, parasitemia, and the clinical course of human P. falciparum malaria. PATIENTS AND METHODS: Forty-seven patients with P. falciparum malaria were evaluated prospectively before and during antiparasitic therapy. TNF alpha serum levels were determined by immunoradiometric assay, PC and TAT plasma antigen by enzyme-linked immunosorbent assay, and PC and PC inhibitor-1 (PCI-1) activity levels by functional tests. Cultured endothelial cells were incubated with serum from four patients with malaria and from healthy control subjects and then assayed for procoagulant activity. Northern blot hybridization was used to detect tissue factor mRNA. RESULTS: In vivo, TNF alpha serum concentrations were elevated (median: 38.6 pg/mL; n = 47) while plasma levels of PC (antigen 55.4%; activity 39.0%; n = 47) and PCI-1 (0.56 U/L) were decreased in almost all patients before antiparasitic treatment. At the same time, TAT concentrations were high. These alterations correlated significantly (p less than 0.01) both with the severity of the disease (as defined by organ impairment) and with the number of circulating parasitized erythrocytes. Low PCI-1 activity correlated with low PC activity (p less than 0.001) and antigen (p less than 0.05) levels. The plasma level of coagulation factor IX, another vitamin K-dependent protein, was not significantly changed. In vitro, incubation of endothelial cells with patient serum (severe P. falciparum malaria) increased both endothelial cell procoagulant activity and cytoplasmic tissue factor mRNA levels. CONCLUSION: Elevated levels of TNF alpha and TAT, decreased plasma levels of anticoagulant PC, and the induction of procoagulant activity in endothelial cells by patient serum indicate a shift in the balance of hemostatic activity towards a procoagulant state in P. falciparum malaria. The alterations in TNF alpha, TAT, and PC levels may be a response to infection, since they correlate with parasitemia and are reversed during antiparasitic treatment. PMID- 1858828 TI - Cerebrovascular accident complicating acute myocardial infarction: incidence, clinical significance and short- and long-term mortality rates. The SPRINT Study Group. AB - PURPOSE: The purpose of this study was to report the incidence, the antecedents, and the clinical significance of clinically recognized cerebrovascular accidents or transient ischemic attacks (CVA-TIA) complicating acute myocardial infarction. PATIENTS AND METHODS: During 1981 to 1983, a secondary prevention study with nifedipine (SPRINT) was conducted in 14 hospitals in Israel among 2,276 survivors of acute myocardial infarction. During the study, demographic, historical, and medical data were collected on special forms for all patients with diagnosed acute myocardial infarction in 13 of these 14 hospitals (the SPRINT registry, n = 5,839). Mortality follow-up was completed for 99% of hospital survivors for a mean follow-up of 5.5 years (range: 4.5 to 7 years). RESULTS: The incidence of CVA-TIA was 0.9% (54 of 5,839). The latter rate increased significantly only with age, from 0.4% among patients up to 59 years old to 1.6% among those aged greater than or equal to 70 years. Multivariate analysis identified age, congestive heart failure, and history of stroke as predictors of CVA-TIA during the acute phase of myocardial infarction. Patients with CVA-TIA exhibited a complicated hospital course, with a 15-day mortality rate of 41%. Subsequent mortality rates in survivors at 1 and 5 years were 34% and 59%, respectively. Rates at the same time points in patients without CVA-TIA were 16%, 11%, and 29% (p less than 0.01). In a multivariate analysis that included age, gender, congestive heart failure, history of previous myocardial infarction, and hypertension, CVA-TIA was independently associated with increased 15-day mortality (covariate-adjusted odds ratio [OR] = 2.62; 90% confidence interval [CI], 1.59 to 4.32), as well as subsequent 1-year (OR = 3.29; 90% CI, 1.70 to 6.36) and long-term (mean follow-up = 5.5 years) mortality (OR = 2.46; 90% CI, 1.30 to 4.69). CONCLUSION: In this large cohort of consecutive patients with myocardial infarction, CVA-TIA was a relatively infrequent complication of acute myocardial infarction. Factors independently favoring the occurrence of CVA-TIA were old age, previous CVA, and congestive heart failure. CVA-TIA occurring during acute myocardial infarction independently increased the risk of early death threefold as well as the risk of long-term mortality in early-phase survivors. (2.5-fold). PMID- 1858830 TI - Coronary heart disease risk factor profiles in black patients with non-insulin dependent diabetes mellitus: paradoxic patterns. AB - PURPOSE: Non-insulin-dependent diabetes mellitus (NIDDM) in black Americans consists of two variants: one with insulin resistance and one with normal insulin sensitivity. This study examined whether cardiovascular disease risk factors are significantly different between the two variants. PATIENTS AND METHODS: Twenty two black patients with NIDDM in near-normoglycemic remission who were receiving no pharmacologic therapy for NIDDM were evaluated for insulin sensitivity by the euglycemic insulin clamp, plasma insulin levels, degree of obesity, glucose metabolism, serum total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels, and fasting plasma triglyceride levels. RESULTS: Fifty-nine percent of these patients had normal insulin sensitivity (glucose disposal rate in response to a 1 mU.kg-1.minute-1 insulin infusion greater than 6.0 mg.kg-1.minute-1). The insulin-sensitive patients were less obese (body mass index [BMI] 26.5 +/- 0.6 versus 30.8 +/- 0.9 kg/m2) and had lower fasting plasma insulin levels (56.9 +/- 7.8 versus 88.0 +/- 6.0 pmol/L), lower serum cholesterol (4.47 +/- 0.30 versus 6.39 +/- 0.26 mmol/L), lower serum LDL cholesterol (2.77 +/- 0.31 versus 4.51 +/- 0.27 mmol/L), and lower fasting plasma triglyceride levels (0.83 +/- 0.08 versus 1.45 +/- 0.16 mmol/L) than the insulin-resistant patients. Serum HDL cholesterol was not different between the two groups and was in the high-normal range (1.31 +/- 0.08 and 1.19 +/- 0.07 mmol/L). Univariate analysis demonstrated that serum total cholesterol, LDL cholesterol, and fasting plasma triglycerides were highly correlated with insulin mediated glucose disposal and fasting plasma insulin. The differences in insulin sensitivity and lipid profiles were independent of obesity, as they were present in six insulin-resistant and six insulin-sensitive patients matched for BMI. CONCLUSIONS: Black patients with the insulin-sensitive variant of NIDDM have a low risk factor profile for cardiovascular disease as compared with those with the insulin-resistant variant, who have a high risk factor profile. A high prevalence of the insulin-sensitive variant of NIDDM in the black population might explain the lower prevalence of angina and myocardial infarction in black patients with NIDDM as compared with white patients with NIDDM. PMID- 1858829 TI - Skeletal integrity in premenopausal and postmenopausal women receiving long-term L-thyroxine therapy. AB - PURPOSE: The impact of long-term L-thyroxine replacement therapy on skeletal integrity is a growing concern because of the large number of women receiving thyroid hormone therapy. The purpose of this study was to examine the hypothesis that long-term L-thyroxine therapy in which the free thyroxine index (FT4I) is maintained within a physiologic range has minimal impact on vertebral or femoral bone mineral density in both premenopausal and postmenopausal women. PATIENTS AND METHODS: We measured hip integral and spinal trabecular and integral bone densities in 28 premenopausal and 28 postmenopausal women who had been receiving L-thyroxine therapy for a median of 12 and 15 years, respectively, and in whom therapy was titrated to keep the FT4I within the normal range. The relationship between bone density parameters and thyroid hormone status was examined using univariate and multivariate statistical methods. RESULTS: Seventy-nine percent of the premenopausal women and 86% of the postmenopausal women had FT4I values in the normal range at the time of bone density determination. Moreover, throughout the study's duration, the majority of annually measured values were in the normal range for more than 80% of subjects. Premenopausal women had slightly lower bone density than would be expected for age: -6.7% (z = -0.39 +/- 0.74 [mean +/- SD], p less than 0.01), -3.1% (z = -0.22 +/- 0.78, p = 0.15), and -5.1% (z = -0.36 +/- 0.74, p less than 0.02) for spinal trabecular, spinal integral, and hip integral bone density, respectively. Postmenopausal women likewise had slightly lower bone density values that were significant only at the hip: -0.2% (z = -0.01 +/- 1.01, p = 0.95), -1.0% (z = -0.05 +/- 1.11, p = 0.80), and -6.2% (z = -0.39 +/- 0.80, p less than 0.02) for spinal trabecular, spinal integral, and hip integral bone density, respectively. When patients with previously treated Graves' disease (n = 4 in each group) were eliminated, the differences in bone density at the hip were no longer seen. Correlation analysis revealed only weak and generally nonsignificant relationships between parameters of thyroid hormone status and bone density at any site in either subgroup. Results of multiple regression analysis among the pooled data of all subjects showed that age provided a consistently significant contribution (R2 = 0.18 to 0.66) to the variability in bone density at the spine and the hip, but parameters of thyroid hormone status did not. CONCLUSION: These data provide the first supportive evidence that long term L-thyroxine therapy that maintains the FT4I in the physiologic range is associated with a statistically significant, but clinically minimal, decrement in spinal and hip bone density in both premenopausal and postmenopausal women. The decrement at the hip was entirely due to the inclusion of patients with treated Graves' diseases. Thus, the changes in bone density in women receiving long-term L-thyroxine therapy are minimal at most and should not be a contraindication to therapy. PMID- 1858832 TI - Is it time for a comprehensive AIDS medical center? PMID- 1858831 TI - A prospective evaluation of elevated serum theophylline concentrations to determine if high concentrations are predictable. AB - PURPOSE: To evaluate prospectively whether serum theophylline concentrations of 25 mg/L and greater were predictable (and presumably preventable) by use of basic pharmacokinetic calculations. DESIGN: Prospective study. PATIENTS: Fifty-five patients with a serum theophylline concentration of at least 25.0 mg/L were evaluated initially and if subsequent elevated theophylline concentrations occurred. INTERVENTIONS: The predicted steady-state serum theophylline concentration was calculated from the dosage rate divided by the predicted clearance to determine how many elevated concentrations (greater than 20 mg/L) were predictable. Predicted clearances were 0.04 L/kg/hour for normal subjects less than 70 years of age and 0.02 L/kg/hour for patients with congestive heart failure, chronic obstructive pulmonary disease, or liver disease. Estimated clearances were determined and compared with predicted clearances. If patients did not have steady-state concentrations, additional calculations were made. MAIN RESULTS: From 6,368 consecutive theophylline determinations, 69 (1.08%) samples from 55 patients were 25 mg/L or higher. Predictably high concentrations occurred in 23 of 33 (69.7%) fully evaluable cases. These concentrations occurred because of a failure to consider decreased elimination clearance from congestive heart failure, chronic obstructive pulmonary disease, or hepatic disease. Five fatalities occurred, and in two cases, theophylline appeared to contribute to the patient's death. Three other patients experienced syncope. The predicted elimination clearance of theophylline of 0.02 L/kg/hour was too high in eight patients over 70 years old with cardiac or pulmonary disease. Nursing and pharmacy oversights were identified as three patients were given two theophylline products simultaneously. CONCLUSIONS: Most elevated theophylline concentrations are predictable (and preventable) by basic pharmacokinetic calculations. Patients experiencing elevated theophylline concentrations often had comorbid conditions and were greater than 60 years of age. The dosage rate of theophylline (mg/hour) can be estimated from predicted clearance (L/kg/hour) times desired steady-state serum concentration (mg/L). PMID- 1858833 TI - Nephrotic syndrome in a 76-year-old man. PMID- 1858834 TI - Spinal epidural abscess caused by group G streptococci. PMID- 1858835 TI - Localized rheumatoid vasculitis presenting as acute alithiasic cholecystitis. PMID- 1858836 TI - Pulmonary infarction associated with crack cocaine use in a previously healthy 23 year-old woman. PMID- 1858837 TI - Reversible pulmonary hypertension associated with anorexigen use. PMID- 1858838 TI - What does time mean to you? PMID- 1858839 TI - Relieving constipation and pain in the terminally ill. PMID- 1858840 TI - Called to testify. PMID- 1858841 TI - Building a critical path for ventilator dependency. PMID- 1858842 TI - Death by choice. PMID- 1858843 TI - Blueprint for restraint-free care. PMID- 1858845 TI - Western states jobfocus. Critical care nursing: action on the western front. PMID- 1858844 TI - How to defeat a 'tet spell'. PMID- 1858846 TI - Mountain states jobfocus. A wide-open world for nursing. PMID- 1858847 TI - Blackie. PMID- 1858848 TI - Clear zone in osteoclast function: role of podosomes in regulation of bone resorbing activity. AB - The adhesion of osteoclasts to the bone matrix is mandatory for bone resorption. Contact of the osteoclast with bone surface induces, in fact, cell polarization and organization of the resorbing apparatus, the so-called "ruffled border." Cell matrix interaction in osteoclasts is a complex phenomenon resulting from formation of the "clear zone," a cytoplasmic area presenting the adhering plasma membrane, or "sealing membrane." The sealing membrane surrounds the ruffled border and seals the resorbing compartment, namely the extracellular space in which bone resorption takes place. Adhesion at this level occurs via specialized discrete structures, the "podosomes." Podosomes present most of the protein commonly found in focal adhesions, but with a peculiar organization. They are dynamic elements suitable for regulation, according with the functional demand of the cell. Their assembly increases during bone resorption and is regulated by the cytosolic free calcium concentration and the activity of protein kinase C. PMID- 1858849 TI - Chronic cobalt causes hypertrophy of glomus cells in the rat carotid body. AB - We tested the hypothesis that chronic cobalt administration would induce carotid body cellular response along with polycythemia as found in chronic hypoxia if common oxygen-sensitive mechanisms were involved in the two instances. Morphometric studies were performed on carotid bodies in male rats that were chronically treated with cobalt chloride (0.17 mumol/kg, ip, daily for 6 wk) and in control rats that received blank saline injections. The rats were anesthetized, blood samples were collected for hematocrit, and the carotid bodies were surgically exposed and were perfused and superfused with the buffered fixative (3% glutaraldehyde plus 1% paraformaldehyde, pH 7.40, 330-340 mosM). The carotid bodies were processed, and ultrathin sections were cut for electron microscopy and morphometry of type I (glomus) and type II cells. Hematocrit increased from 44% in the control to 74% in the cobalt-treated rats, and the mean volume of type I cells increased from 424 to 1,061 microns 3. Type II cells did not show any significant change in size. The results suggest that cobalt stimulated oxygen-sensitive mechanism in the glomus cells of the carotid body and that the glomus cell is a site of oxygen chemosensing. PMID- 1858850 TI - Inwardly rectifying potassium current in mammalian lens epithelial cells. AB - Lens potassium conductance is essential for the maintenance of lens volume and transparency. Recent work has identified three major potassium currents in lens: 1) an outwardly rectifying current, 2) an inwardly rectifying current, and 3) a calcium-activated current. This paper presents a study of the lens inward rectifier using whole cell and single-channel patch-clamp techniques. Inwardly rectifying potassium current is present in isolated human, rabbit, rat, and mouse lens epithelia. The voltage about which rectification occurs depends on the external potassium concentration. Internal magnesium is not necessary for rectification. In physiological saline, a time-dependent decrease in current during sustained hyperpolarization is seen. This "droop" is due to voltage dependent block by external sodium. The inward rectifier is also effectively blocked by external cesium or barium but not by tetraethylammonium or 4 aminopyridine. The mouse lens inward rectifier has a single-channel conductance of 32 pS (measured on-cell with 150 mM potassium in the pipette). The single channel current-voltage relationship is linear in the inward direction. In contrast to the macroscopic case, no outward current was measurable. The inward rectifier in lens has the necessary properties to be involved in setting resting voltage. PMID- 1858851 TI - pHi regulation in frog retinal pigment epithelium: two apical membrane mechanisms. AB - This study demonstrates that the apical membrane of frog retinal pigment epithelium (RPE) contains two intracellular pH (pHi) regulatory mechanisms, an electrogenic Na-HCO3 cotransporter blocked by DIDS and an amiloride-inhibitable Na-H antiporter. pHi was studied using the pH-sensitive dye 2',7'-bis(2 carboxyethyl)-5,6-carboxyfluorescein (BCECF). In these cells resting pHi equals 7.26 +/- 0.09 (n = 58). After an acid load (NH4Cl prepulse), pHi recovery required apical extracellular Na concentration ([Na]o) in HCO3 or HCO3-free Ringer. In HCO3 Ringer recovery was completely blocked by 1 mM apical DIDS (n = 5) but was not affected by absence of Cl. In HCO3-free Ringer, recovery was completely blocked by 1 mM apical amiloride (n = 3). At resting pHi, the intrinsic pH-buffering capacity of the cell is approximately 7.1 mM/pH and rises monotonically as pHi decreases. In HCO3 Ringer, the initial rate of acidification caused by apical Na removal, 0.39 +/- 0.03 pH/min (n = 26), was 80-90% inhibited by apical DIDS (n = 5) and 16% inhibited by 1 mM apical amiloride (n = 7), but not affected by absence of Cl. In HCO3 Ringer, initial rates of acidification induced by apical DIDS or amiloride were 0.11 +/- 0.06 (n = 5) and 0.03 +/- 0.02 pH/min (n = 7), respectively. These results indicate that the Na-HCO3 cotransporter accounts for 80-90% of the acid extrusion from frog RPE cells. Increasing apical [K]o from 2 to 5 mM approximates the in vivo apical [K]o changes during a light-dark transition and alkalinizes the cells. [K]o-induced alkalinization had an initial rate of 0.11 +/- 0.02 pH/min (n = 16), which was approximately 75% inhibited by apical DIDS (to 0.04 +/- 0.01 pH/min, n = 7) and completely blocked by HCO3/CO2 removal from both bathing solutions. [K]o-induced pHi changes alter RPE transport mechanisms and may affect RPE-photoreceptor interactions. PMID- 1858852 TI - Prolonged incubation of skeletal muscle in vitro: prevention of increases in glucose transport. AB - During experiments involving prolonged incubation of skeletal muscle, we observed large increases in glucose transport activity. The basal rate of 3-O methylglucose (3-MG) transport increased two- to fourfold in rat epitrochlearis muscles incubated for 9 h without insulin in Krebs-Henseleit buffer supplemented with 8 mM glucose. The stimulatory effect of a low concentration of insulin (30 microU/ml, added during the final 30 or 60 min of incubation) on glucose transport activity was enhanced 2.5-fold after 6 h and approximately 5-fold after 9 h of incubation. Exposure of muscles to 100 microU/ml of insulin for the first 8 h inhibited slightly but significantly the increase in insulin-stimulated 3-MG transport over a 9-h incubation period. Incubation of muscles in minimal essential medium (MEM) for 9 h inhibited the time-dependent rise in basal and insulin-stimulated transport by approximately 45%. The effect of MEM was reproduced with MEM essential, but not nonessential, amino acids. Incubation of muscles with MEM plus 100 microU/ml of insulin for the first 8 h prevented the increases in 3-MG transport activity measured after a 9-h incubation period. Muscles incubated for 9 h maintained ATP and phosphocreatine concentrations, and changes in glycogen concentrations were small. Thus we have defined conditions for long-term incubation of skeletal muscle under which a progressive increase in glucose transport is prevented. PMID- 1858853 TI - Reduced glycolytic metabolism in regenerated fast-twitch skeletal muscle. AB - Freely grafted rat extensor digitorum longus (EDL) muscles were subjected to low frequency stimulation in an anaerobic environment to determine whether regenerating fast-twitch muscles regain normal glycolytic metabolic capacity. Regenerating muscles were tested at 28, 42, and 76 days after the graft procedure. Stabilized grafts (76 days) produced approximately 60% of the lactate generated by intact, control EDL subjected to the same stimulus paradigm and developed half the estimated increase in H+. The grafts exhibited the same relative decline in force after 5 min of anaerobic stimulation as control EDL but maintained relatively constant levels of ATP while consuming phosphocreatine. This study indicates that regenerating fast-twitch skeletal muscle has a reduced ability to initiate glycolytic activity during exercise. The data also indicate that a small population of regenerating fast-twitch fibers express the slow isoform of myosin heavy chain (beta-MHC) with maximum expression occurring at 56 days postsurgery. PMID- 1858854 TI - Rapid increase in inositol phosphate levels in norepinephrine-stimulated vascular smooth muscle. AB - We examined the correlation between agonist-stimulated increases in inositol phosphates and force development in vascular smooth muscle. Segments of rat tail artery were preincubated with [3H]inositol and treated with norepinephrine (10( 5) M) for 3-10 s. Tissue levels of inositol monophosphate (IP), inositol bisphosphate (IP2), and inositol trisphosphate (IP3) were measured. IP and IP2 increased significantly after 3 s of norepinephrine treatment. IP3 increased significantly after 5 s of norepinephrine treatment. Analysis of tissue extracts by high-pressure liquid chromatography demonstrated that the only isomer of IP3 present in any tissue extract was the 1,4,5-isomer [Ins(1,4,5)P3]. Contractile response to norepinephrine stimulation showed that the increase in inositol phosphates coincides well with the time course of force development. This is the first report demonstrating such an early increase in Ins(1,4,5)P3 in agonist stimulated vascular smooth muscle. These results are consistent with the hypothetical role of Ins(1,4,5)P3 as a mediator linking agonist-receptor activation to increased intracellular calcium and force development in norepinephrine-stimulated vascular smooth muscle. PMID- 1858855 TI - Agonist-induced frequency modulation of Ca2+ oscillations in salt gland secretory cells. AB - Oscillations in intracellular calcium concentration ([Ca2+]i) induced by the acetylcholine analogue carbachol (CCh) were characterized by microspectrofluorimetry of fura-2 in single secretory cells from the avian salt gland. The frequency of oscillations increased in graded fashion with [CCh] between 25 nM (2.7 +/- 0.6 min-1) and 250 nM (11.8 +/- 1.4 min-1), whereas the amplitude of the spikes was independent of [CCh]. An interperiod return to prestimulatory [Ca2+]i was generally seen only at very low (25 nM) CCh. Between 50 and 250 nM CCh, oscillations were associated with sustained elevated [Ca2+]i levels. The amplitude of the oscillatory spikes was found not to exceed that of initial spikes arising from prestimulatory [Ca2+]i, despite the dose-dependent [effective concentration at 50% (EC50) = 200 nM CCh] sustained rise in [Ca2+]i. At 1 microM CCh, oscillations gave way to a maximal sustained increase in [Ca2+]i. Reduction of [Ca2+]o to 1.5 microM during an oscillatory train or blockage of Ca2+ influx with Ni+ resulted in a reduction in sustained Ca2+i levels and in frequency, but not amplitude, of oscillations. A relationship between the sustained partial rise in [Ca2+]i derived from Ca2+ influx and the oscillatory frequency at a given [CCh] was further indicated by the lower frequency (P less than 0.01) of the early spikes in a train when interspike [Ca2+]i initially returned to near-basal levels. In some cells, oscillations were slow enough (less than 2 min-1) to resolve an interperiod of elevated baseline [Ca2+]i, showing that the latter can occur independent of the repetitive Ca2+ spikes. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858856 TI - Na-Ca exchange: evidence against a ping-pong mechanism and against a Ca pool in ferret red blood cells. AB - To determine the mechanism of Na-Ca exchange, we estimated the ratio of maximum velocity to Michaelis constant for extra-cellular Ca by measuring the rate of Ca uptake at very low extracellular Ca. In a Ping-Pong mechanism, one set of sites alternatively transports Ca and Na. In a sequential mechanism, Ca and Na sites are both filled during part of the transport cycle. In each set of experiments, two intracellular Na concentrations were studied. The Ca uptake rate (at low Ca) increased as Na increased; this is consistent with a sequential model, as has been found in other cells. We also examined the alternative hypothesis that the exchanger followed Ping-Pong kinetics and that the red blood cells had a submembrane pool for Ca that limited mixing with the cytosol. In these experiments Ca pump activity was monitored by measuring ATP hydrolysis. This model was disproven by experiments that indicated that greater than 80% of the Ca that entered the cell became bound to EGTA and less than 20% resulted in Ca efflux by the Ca pump. PMID- 1858857 TI - Depression of delayed outward K+ current by Co2+ in guinea pig ventricular myocytes. AB - Effects of Co2+ on the delayed outward K+ current (IK) in guinea pig ventricular myocytes were studied using the whole cell patch-clamp technique. IK was activated by depolarizing voltage pulses positive to -30 mV and reached half maximal activation at +24 mV. Co2+ shifted the activation curve to a more depolarized voltage range in a concentration-dependent manner, with a Co2+ concentration at which half-maximal response occurs (IC50) of 8 mM and a saturation value of +38 mV. The voltage dependency of IK gatings showed a shift similar to that of activation. In both cases the shift could be explained by screening of surface potential. The density of total negative surface charges sensed by Co2+ was estimated to be 1 e/225 A2. Co2+ also reduced the fully activated IK [IK(full)], and the dose-response curve had a Hill coefficient of 0.5 and an IC50 of 1 mM at 0 mV. Depression of IK(full) was mainly voltage independent. The single-channel unitary current estimated by fluctuation analysis was approximately 0.1 pA at -30 mV either in the absence or presence of Co2+. Therefore, the depression of IK(full) is due to an equivalent reduction in the number of functional channels. It is concluded that Co2+ depressed IK through multiple mechanisms. PMID- 1858858 TI - Regulation of permeabilized endothelial cell retraction by myosin phosphorylation. AB - Permeabilized endothelial cell monolayers retracted on exposure to ATP and Ca2+. ADP, inosine triphosphate (ITP), GTP, adenosine 5'-(gamma-thio)triphosphate (ATP gamma S), and 5'-adenylylimidodiphosphate failed to support retraction. However, ATP gamma S, a substrate for myosin light-chain kinase (MLCK) but not myosin adenosinetriphosphatase (ATPase), combined with ITP, a substrate for myosin ATPase but not MLCK, supported retraction. Two MLCK pseudosubstrate peptides, M5 and SM-1, inhibited endothelial cell retraction equally and more effectively than myosin kinase-inhibitory peptide with a sequence based on the phosphorylated site of myosin light chain. M5 was shown to inhibit thiophosphorylation of endothelial cell myosin light chains. Endothelial cells incubated with exogenous unregulated kinase in the presence of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N' tetra-acetic acid retracted on addition of ATP. This retraction was accompanied by thiophosphorylation of the 19 kDa myosin light chains in the presence of ATP gamma 35S. The N-ethylmaleimide-modified subfragment 1 of myosin heads, a specific inhibitor of actin-myosin interaction, prevented retraction. These data add support to the proposal of a central role for MLCK activation of myosin in endothelial retraction. PMID- 1858859 TI - Relaxation, [Ca2+]i, and the latch-bridge hypothesis in swine arterial smooth muscle. AB - During vascular smooth muscle relaxation, myosin light-chain phosphorylation values decrease to resting values more rapidly than do stress values. Because phosphorylation is proportionally low, the latch-bridge hypothesis predicts that stress during relaxation should be predominantly carried by latch bridges. I evaluated the mechanical properties of latch bridges by changing tissue length and measuring myoplasmic Ca2+ concentration ([Ca2+]) with aequorin during relaxation of swine carotid medial tissues. Stress production was predicted with the latch-bridge model of Hai and Murphy, in which the measured aequorin [Ca2+] signal is the only determinant of stress. The aequorin-based latch-bridge model predicted relaxation induced by removal of the histamine stimulation. However, when tissues were relaxed by removal of extracellular Ca2+ or Ca(2+)-channel blockers in the continued presence of histamine, the aequorin-based model modestly underestimated the resulting relaxation. This underestimation was most likely caused by a small increase in the [Ca2+] sensitivity of phosphorylation since a model with an altered [Ca2+] sensitivity of phosphorylation more accurately predicted the resulting relaxation. The time course of relaxation in swine carotid artery was not substantially altered when the tissue was either briefly stretched or shortened and then returned to the original length. Because stretch should detach cross bridges, I modified the aequorin-based latch-bridge model to account for stretch-induced cross-bridge detachment. Because [Ca2+] values were slightly above resting values both before and after the stretch, the model predicted that phosphorylated cross bridges could reattach, be dephosphorylated, and form new latch bridges. The model predicted relaxation except during the first few seconds after stretch. These results suggest that latch-bridge reattachment is not necessary to explain the majority of the response to stretch during relaxation. The rate-limiting step for relaxation appears to be removal of [Ca2+] and not latch-bridge detachment. PMID- 1858860 TI - Carbohydrate supplementation attenuates IMP accumulation in human muscle during prolonged exercise. AB - The effect of carbohydrate (CHO) ingestion on metabolic responses to exercise has been investigated. Subjects cycled at approximately 70% of maximal oxygen uptake to fatigue [135 +/- 17 (+/- SE) min] on the first occasion (control, CON) and at the same work load and duration on the second occasion but with addition of ingestion of CHO during the exercise. Biopsies were taken from the quadriceps femoris muscle before and after exercise. The sum of the hexose monophosphates (HMP), as well as lactate and alanine, in muscle was higher after CHO exercise (P less than or equal to 0.05, P less than or equal to 0.05, and P less than or equal to 0.01, respectively). Acetylcarnitine increased during exercise but was not significantly different between treatments after exercise (CON, 6.6 +/- 1.7; CHO, 10.0 +/- 1.2 mmol/kg dry wt; P = NS). The sum of the tricarboxylic acid cycle intermediates (TCAI; citrate + malate + fumarate) was increased during exercise and was higher after CHO exercise (2.34 +/- 0.32 vs. 1.68 +/- 0.17 mmol/kg dry wt; P less than or equal to 0.05). IMP was less than 0.1 mmol/kg dry wt at rest and increased to 0.77 +/- 0.26 (CON) and 0.29 +/- 0.11 mmol/kg dry wt (CHO) (P less than or equal to 0.05) during exercise. It was recently found that during prolonged exercise there is initially a rapid and large expansion of TCAI and glycogenolytic intermediates in human muscle followed by a continuous decline in TCAI and glycogenolytic intermediates [K. Sahlin, A. Katz, and S. Broberg. Am. J. Physiol. 259 (Cell Physiol. 28): C834-C841, 1990].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858861 TI - Differences between OK and LLC-PK1 cells: cystine handling. AB - Cultured opossum kidney (OK) and porcine kidney (LLC-PK1) cells were compared for biochemical characteristics and cystine transport systems. The cell lines differ in amount of protein per cell, with OK cells having approximately one-half the amount found in LLC-PK1. Both cell lines contain 19 micrograms DNA/10(6) cells. As cells reach confluence, cystine uptake increases in OK and decreases in LLC PK1 cells. Throughout the growth period, only lysine inhibits cystine uptake in OK, whereas glutamate is the inhibitor in LLC-PK1. The predominant site of cystine transport in OK cells is across the apical membrane, and the basolateral membrane is the corresponding site of transport in LLC-PK1 cells. Although the intracellular reduced glutathione pool is the same, the cysteine pool in OK cells is approximately one-fourth that found in LLC-PK1 cells. The ability of OK cells to reflect the shared cystine-dibasic amino acid transport system and LLC-PK1 to exhibit the cystine-glutamate antiporter system makes available two models for investigation of the development and structure of cystine transport systems. PMID- 1858862 TI - Frog semitendinosis tendon load-strain and stress-strain properties during passive loading. AB - The mechanical properties of the frog semitendinosis (ST) tendon, bone-tendon junction, and aponeurosis were measured during passive loading to a tension equal to maximum isometric tension (Po). Stiffness and strain in these regions continuously increased as load increased. Tendon stiffness was approximately four times the aponeurosis stiffness. Tendon Young's modulus at Po was only 188 MPa, which is approximately 10 times less than the modulus reported for most mammalian tendons. Similarly, tendon stress at Po was only approximately 3 MPa, which is also less than that predicted for many tendons. Tendon strain at Po was approximately 2% after passive loading. We conclude that different regions of the frog ST tendon have different mechanical properties and that the frog ST tendon operates physiologically in the "toe" region of the stress-strain curve with a variable stiffness that increases with load. Taken together, these results have significant implications in understanding muscle-tendon design and neuromotor control strategies. PMID- 1858863 TI - MHC composition and enzyme-histochemical and physiological properties of a novel fast-twitch motor unit type. AB - Determinations of fatigue ratio, twitch and tetanus tension, and contraction and half-relaxation times of the isometric twitch were made in 21 single fast-twitch motor units from the rat tibialis anterior muscle. Single motor units were functionally isolated by microdissection of the ventral root, and the glycogen depletion technique was used to demonstrate the muscle fibers in the unit. Morphological and immuno- and enzyme-histochemical methods were applied to serial muscle cross sections to characterize the muscle fibers in the unit. Three of the units had muscle fibers of the IIa type according to staining both for myofibrillar adenosinetriphosphatase after acid preincubation and with the use of monoclonal antibodies specific for myosin heavy chains (MHCs), i.e., the IIa-MHC isoform. The other 18 units were of the IIb type according to enzyme histochemistry, but immunohistochemistry showed that in six of these units the muscle fibers exhibited the novel type IIx-MHC isoform and in the other 12 units the IIb-MHC isoform. It was found that the IIx motor units have contraction and half-relaxation times similar to those of types IIa and IIb units but have morphological, physiological, and biochemical properties that distinguish them from the latter two types. PMID- 1858864 TI - Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits. AB - A reduction in nerve blood flow in chronic experimental diabetes has been linked to impaired conduction. Recently, there have been reports that this is preceded by a period of functional hyperemia. The present investigation explored early changes in sciatic nerve endoneurial blood flow and function in streptozocin treated rats with durations of diabetes from 1 wk to 4 mo. Blood flow was monitored by microelectrode polarography and hydrogen clearance in thiobutabarbital (Inactin)-anesthetized animals. It was reduced by 41% as early as 1 wk after diabetes induction. There was no evidence of an early functional hyperemia, flow remaining 44% depressed up to 4 mo. In another investigation, similar reductions in blood flow were acutely induced in normal rats rendered hyperglycemic by glucose infusion. In diabetic animals, conduction velocity in sciatic branches supplying gastrocnemius and tibialis anterior muscles was correlated with blood flow. The link was further tested using a group of 2-mo diabetic rats treated with guanethidine. Treatment caused a functional adrenergic sympathectomy, and blood flow increased to within the normal range. Conduction velocity, depressed by 26% with diabetes, was normalized by treatment. These observations support the hypothesis that hyperglycemia-induced blood flow reductions and resultant endoneurial hypoxia are important factors underlying nerve conduction deficits early in the development of diabetic neuropathy. PMID- 1858865 TI - Measuring body fat: calibrating the rulers. Intermethod comparisons in 389 normal Caucasian subjects. AB - A systematic study of 389 normal Caucasians stratified for sex and age compared all of the traditional methods for measuring fat: body water, underwater weighing, body potassium, and anthropometrics and the newer methods of dual photon absorptiometry, bioimpedance analysis, and total body electrical conductivity. Measurements by all methods are highly intercorrelated, but methods differences show the population means for fat percent to range from 26 to 35% of body weight across eight methods. All methods show increasing fat (as % body weight) with age in both sexes but vary in secular slope. The goal of this report is to provide direct translations between each of the eight methods. Intermethod comparison equations are given as simple linear regressions by using each method both as dependent and independent variable for each sex, permitting translation for results by any method to any other. PMID- 1858866 TI - Differential effects of omega-3 fish oils on protein kinase activities in vitro. AB - We studied the in vitro effects of omega-3 fish oils and other fatty acids on the activity of crude protein kinase C from S49 lymphoma cells, on partially purified enzyme from rat cerebrum, on homogeneous protein kinase C from bovine brain, and, for comparison, on type I adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. In the absence of exogenous phospholipid, the fish oils cis 5,8,11,14,17-eicosapentaenoic acid (EPA) and acid (DCHA) enhance the catalytic cis-4,7,10,13,16,19-docosahexaenoic activity of protein kinase C and support the binding of [3H]phorbol 12,13-dibutyrate, both to approximately 50% of the level supported by phosphatidylserine. In the presence of phosphatidylserine, the omega 3 fatty acids reduce catalytic activity and [3H]phorbol 12,13-dibutyrate binding by about one-half. The effects of the omega-3 fatty acids on enzyme activity suggest that fish oils act as partial agonists competitively with phosphatidylserine. EPA, DCHA, and arachidonate (but not a variety of saturated fatty acids) inhibit the cAMP-dependent protein kinase. Thus dietary fish oils and cellular fatty acids mobilized by the action of phospholipase A2 may differentially modulate the activities of protein kinase C and cAMP-dependent protein kinase. These data suggest means by which unsaturated fatty acids mobilized within cells may act as second messengers. PMID- 1858867 TI - Kinetics of copper metabolism in rats: a compartmental model. AB - Model-based compartmental analysis was used to describe data on the whole body kinetics of copper metabolism in rats. Data were collected on recovery of radio copper in plasma, liver, skin, skeletal muscle, bile, and feces for 3 days after the injection of 10 micrograms iv of copper labeled with 64Cu. Data on copper masses and on 64Cu kinetics were analyzed by the stimulation, analysis, and modeling computer programs. Observed data were fit to a 16-component "working hypothesis" model; fractional transfer coefficients were estimated, and steady state compartment masses and copper transfer rates were calculated. The model postulates a rapid turnover of plasma nonceruloplasmin (NCp) copper (8.5 h-1), which exchanged a large amount of copper with extrahepatic tissues (16 micrograms/h) as well as liver (13 micrograms/h). In comparison, ceruloplasmin (Cp) transferred relatively little copper to tissues (less than 1 microgram/h). NCp copper is postulated to be the precursor for biliary copper. Regarding the intracellular metabolism of copper in hepatic and extrahepatic tissues, the data were compatible with a faster turning-over compartment that exchanged copper with NCp and a slower turning-over compartment with input from Cp. In the liver, the slower turning-over compartment was the copper present in peak II (mol mass 30,000-40,000 Da); this received much of its input from the faster turning-over compartment (peak III), which was hypothesized to represent, in large part, copper in metallothionein. PMID- 1858868 TI - Adrenal steroid receptor activation in vivo and immune function. AB - Recent studies have indicated significant differences among immune and other tissues in in vivo adrenal steroid receptor activation after a given hormone exposure. Nevertheless, the relationship between in vivo receptor activation and functional measures of the immune response has not been determined. Type I and type II adrenal steroid receptor binding in conjunction with mitogen-induced T cell proliferative responses were measured in the spleens of Sprague-Dawley rats that were administered various concentrations of dexamethasone (DEX). A linear relationship between type II receptor binding and splenocyte proliferation was found, with decreases in measurable type II receptors (indicating in vivo receptor activation) being highly correlated with decreases in immune function. There was no evidence of spare type II receptors. In vitro studies using the type II receptor antagonist RU 486 confirmed that the inhibitory effect of DEX on splenocyte proliferation was mediated via the type II receptor. These findings provide a foundation for future studies evaluating glucocorticoid effects on immune system function and suggest that evidence of in vivo receptor activation may be critical for predicting when and in which tissues adrenal steroid hormones may be capable of modulating the immune response. PMID- 1858869 TI - Dose-response characteristics of impaired glucose oxidation in non-insulin dependent diabetes mellitus. AB - To determine the dose-response characteristics of impaired glucose oxidation in non-insulin-dependent diabetes mellitus (NIDDM), indirect calorimetry was performed on eight matched control and NIDDM subjects during the basal state and during three glucose clamps at insulin infusion rates of 150, 300, and 1,500 pmol.m-2.min-1. Hyperglycemia was used to achieve matched rates of glucose uptake at each insulin infusion. Glucose uptake in the basal state was greater in NIDDM [3.75 +/- 0.23 vs. 2.50 +/- 0.10 mg.kg fat-free mass (FFM)-1.min-1, P less than 0.005] but was similar at approximately 8, 12, and 26 mg.kg FFM-1.min-1 at each insulin infusion. Basal protein oxidation, fat oxidation, and plasma free fatty acids were similar and equally sensitive to suppression by insulin in both groups. Glucose oxidation was reduced 20-26%, and circulating lactate increased 50-90% at physiological but not at pharmacological insulin concentrations in NIDDM. The dose-response relationship between serum insulin and glucose oxidation was right shifted in NIDDM with half-maximal activation at 368 +/- 91 vs. 179 +/- 27 pM in controls (P less than 0.05). In conclusion, glucose oxidation is reduced at physiological insulin concentrations in NIDDM and cannot be explained by concomitant obesity, increased fat oxidation, or reduced glucose uptake but results from impaired sensitivity to stimulation by insulin, possibly at pyruvate dehydrogenase. PMID- 1858870 TI - Cytosolic calcium responses of single rMTC 44-2 cells to stimulation with external calcium and potassium. AB - Few endocrine tissues can detect changes in the extracellular Ca2+ concentration within the physiological range and modify their hormone secretion accordingly. A rat cell line of C-cell origin (rMTC 44-2) secretes calcitonin and neurotensin in response to small increases in external Ca2+. To better understand the mechanism of extracellular Ca2+ sensing in this cell type, we studied single fura-2-loaded rMTC 44-2 cells perfused with increasing concentrations of Ca2+ and K+. In the basal state (Ca2+ = 0.5 mM), cytosolic Ca2+ levels were 53 nM, with 27% of the cells having spikes or oscillations. With elevation of the external Ca2+ to between 0.5 and 4 mM, 84% of the cells showed a rapid (less than 5 s) rise in cytosolic Ca2+ to values 2- to 10-fold higher than basal levels. Most of the responding cells exhibited complex patterns of cytosolic Ca2+ fluctuations, including oscillations with frequencies varying from less than 1/min to as many as 6/min. When averaged over time, the cytosolic Ca2+ of individual cells showed a dose-dependent response with changes in external Ca2+, resembling the relationship between extracellular Ca2+ and calcitonin secretion. With continued or repeated stimulation, the spike amplitude often declined. These cytosolic Ca2+ responses were attenuated in the presence of the Ca(2+)-channel blockers cadmium and nifedipine. Cytosolic Ca2+ responses to perfusion with elevated K+ (20 mM) were similar in waveform to those seen with Ca2+ stimulation. Most cells displayed cytosolic Ca2+ changes in response to both ionic secretagogues when stimulated with external Ca2+ or K+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858871 TI - Splanchnic osmosensation and vasopressin: mechanisms and neural pathways. AB - Hypertonic (2 ml, 598 mosmol/kgH2O) solutions were infused over 4 min via a stomach tube in 12 groups (n = 5-10) of conscious rats with indwelling arterial catheters. Mean changes over 4-21 min of plasma arginine vasopressin (AVP) were 6.1 +/- 0.9 for NaCl (P less than 0.01), 9.3 +/- 3.0 for LiCl (P less than 0.01), 4.5 +/- 1.3 for sodium isethionate (P less than 0.01), 2.8 +/- 0.9 for sucrose (P less than 0.025), 3.9 +/- 2.8 for mannitol (P less than 0.01), and -0.1 +/- 0.1 (SE) pg/ml for urea. The AVP responses to NaCl and sucrose were proportional to the rate of gastrointestinal absorption of radiolabeled NaCl and sucrose, respectively. The AVP response to 598 mosmol/kgH2O NaCl was attenuated by 60.6% (P less than 0.001) in rats with lesion of the side branches of the major splanchnic nerves innervating the mesentery of the upper small intestine and the portal vein area, by 34-37% (P less than 0.05) in rats with right or left splanchnic nerve lesions, and was not affected by subdiaphragmatic vagotomy. Changes in systemic plasma osmolality were small and could not explain the AVP responses. Thus splanchnic receptors are osmosensitive, are situated in the mesentery of the upper small intestine and possibly the portal vein area, and project to the spinal cord via the right and left major splanchnic nerves. PMID- 1858872 TI - Response of rat selenoprotein P to selenium administration and fate of its selenium. AB - Selenoprotein P is a glycoprotein that contains greater than 60% of the selenium in rat plasma. Physiological experiments were undertaken to gain insight into selenoprotein P function. Selenium-deficient rats were injected with doses of selenium ranging from 25 to 200 micrograms/kg, and the appearance of selenoprotein P was compared with the appearance of glutathione peroxidase activity in plasma and in liver. Selenoprotein P concentration increased to 35% of control by 6 h, whereas glutathione peroxidase activity increased minimally or not at all. Moreover, in rats given 100 and 200 micrograms selenium/kg, selenoprotein P reached 75% of its concentration in control rats at 24 h, whereas glutathione peroxidase activity reached only 6% of control. Cycloheximide pretreatment blocked the appearance of selenoprotein P in response to selenium injection. Male and female rats had similar concentrations of selenoprotein P. Partially purified selenoprotein P and plasma glutathione peroxidase labeled with 75Se were administered intravenously to selenium-deficient and control rats. 75Se given as selenoprotein P disappeared more rapidly from plasma than did 75Se given as glutathione peroxidase. Selenium deficiency did not significantly affect 75Se disappearance from plasma. At 2 h, brain, but not other tissues, took up more 75Se in selenium-deficient rats than in control rats when 75Se was given as selenoprotein P. This suggests that brain has a specific uptake mechanism for selenium given in the form of selenoprotein P. These results demonstrate that several physiological properties distinguish selenoprotein P from glutathione peroxidase. However, they do not clearly indicate its function. PMID- 1858873 TI - Hypoinsulinemia is not critical to glucose recovery from hypoglycemia in humans. AB - To test the hypothesis that glucose recovery from hypoglycemia can occur in the absence of decrements in insulin below baseline, we studied nine normal humans on six occasions. In a control study, saline was infused. In five experimental studies, insulin (0.6 mU.kg-1.min-1) was infused from 0 to 80 min, to produce hypoglycemia (approximately 3.3 mM). Then, from 80 to 180 min, insulin was not infused or was infused in four different doses 0.1, 0.2, 0.4, and 0.6 mU.kg-1.min 1), and glucose recovery was assessed. In the recovery periods, approximately fourfold peripheral with approximately twofold portal insulin elevations prevented glucose recovery (glucose = 3.6 +/- 0.1 mM, counter-regulatory hormone levels elevated throughout). However, biological glucose recovery, documented by increments to 4.3 +/- 0.1 mM and decrements in all counterregulatory hormones (glucagon, epinephrine, growth hormone, and cortisol) to control levels, occurred despite nearly twofold peripheral hyperinsulinemia (54 +/- 4 vs. 32 +/- 4 pM, P less than 0.01) in the absence of portal hypoinsulinemia (58 +/- 4 vs. 68 +/- 8 pM). Thus we conclude that, although dissipation of insulin normally plays an important role in the correction of hypoglycemia, biological glucose recovery from hypoglycemia to glucose levels more than sufficient to disengage glucose counterregulatory systems and well above those required to produce symptoms of hypoglycemia can occur in the absence of decrements in portal insulin below baseline and despite mild peripheral hyperinsulinemia. PMID- 1858874 TI - Nuclear calcium gradients in cultured rat hepatocytes. AB - Ca2+ concentrations ([Ca2+]) in cytosol and nucleus in fura-2-loaded cultured rat hepatocytes were determined by three-dimensional (3-D) optical-sectioning microscopy. After determining the empirical 3-D point spread function of the fluorescence microscope-coupled digital video imaging system, contaminating light arising from optical planes above and below the plane of interest was removed by deconvolution using the nearest-neighboring approach (NNA) algorithm. Although deconvolution resulted in substantial improvement in accuracy of fluorescence intensity determinations in single-wavelength excitation images as well as sharper delineation of boundaries between cellular compartments, the complicated mathematical process did not significantly enhance the precision of [Ca2+] values derived from ratiometric (ratio of dual-wavelength excitation) images. In resting hepatocytes, cytosolic Ca2+ (210 +/- 15 nM) was 1.6- to 2-fold higher than nuclear Ca2+ (128 +/- 12 nM). This difference in Ca2+ between the two compartments was detected both in raw ratiometric images and in those processed with NNA algorithm. Addition of arginine vasopressin or epidermal growth factor resulted in significant increases (2- to 3-fold) in both cytosolic and nuclear Ca2+; however, the nuclear-to-cytosolic Ca2+ gradient was preserved in hepatocytes stimulated with mitogens. We conclude that the hepatocyte nuclear membrane contains Ca2+ permeability barriers and Ca2+ transport mechanisms that may be hormonally sensitive. We postulate that the increase in nuclear Ca2+ may be important in regulation of cell proliferation induced by mitogens, possibly by activating Ca(2+)-dependent endonucleases, nuclear calmodulin, or nuclear protein kinase C. PMID- 1858875 TI - Evidence for a delayed rectifier-like potassium current in the clonal rat pituitary cell line GH3. AB - Whole cell patch-clamp techniques were used to investigate voltage-dependent potassium currents in the clonal rat pituitary cell line GH3. Inactivation of the voltage-dependent potassium current was best fit by two time constants (50-80 ms and 2-3 s) plus a sustained value. These components of inactivation could be separated based on their voltage-dependent properties and pharmacological sensitivity to 10 mM tetraethylammonium (TEA) and 5 mM 4-aminopyridine (4-AP). The fast component begins to activate around -50 mV, is half-maximally activated at -19 mV, is 50% inactivated at -55 mV, and is sensitive to 4-AP but insensitive to TEA. The slow component begins to activate at around -10 mV, is half-maximally activated at +4 mV, is 50% inactivated at -23 mV, and is sensitive to both TEA and 4-AP. The sustained component is apparent by 0 mV but has not yet reached half-maximal activation at +57 mV. It is somewhat sensitive to TEA but relatively resistant to 4-AP. In the presence of TEA it was found that the fast-inactivating component actually inactivated in a biphasic manner with time constants of approximately 50 and 500 ms. From the properties of these components it is concluded that at least three distinct voltage-dependent potassium channel types exist in GH3 cells as follows: an A-like current (fast-inactivating component), a delayed rectifier-like current (slow-inactivating component), and the voltage dependent properties of calcium-dependent potassium channels (the sustained component). PMID- 1858876 TI - Metabolism of oleic acid in differentiating BFC-1 preadipose cells. AB - Incorporation of [3H]oleate and [14C]glucose into cellular lipids was studied in the preadipose cell line BFC-1 to determine flux changes that accompany the adipose conversion process. Dilution of oleate by intracellular fatty acids (FA) was estimated from the 3H/14C incorporation ratios and from relating steady-state radioactivity in diglycerides to their measured cellular levels. The data indicated that exogenous FA mixed with less than 1% of endogenous FA on its pathway to esterification. Conversion of preadipocytes to adipocytes increased uptake of FA and glucose by approximately 3-fold and synthesis of diglycerides and triglycerides by 5- and 16-fold, respectively, with little if any increase of phospholipid synthesis. A 50% drop in 3H/14C incorporation ratio indicated a doubling of the rate at which endogenous FA mixed with the exogenous FA that had entered the cell. Adipocytes compared with preadipocytes exhibited a 50% greater cell diameter and a doubling of intracellular water volume and of protein and phospholipid levels, reflecting cellular enlargement consequent to the arrest of cell division that precedes adipose conversion. Diglyceride levels were also increased in adipocytes, however, since their turnover was fast, as indicated by rapid equilibration of diglyceride labeling; the increase reflected changes in their relative rates of synthesis and disposal. Diglyceride levels related to cell phospholipid, and other indexes of cell size remained constant. This indicated that the supply of diglycerides was tightly coupled to the synthesis of triglycerides and phospholipids, which suggested feedback regulation of diglyceride formation. The studies provide a methodological approach to measurement and interpretation of rates of lipid deposition in cultured cells. PMID- 1858877 TI - Muscle insulin resistance in uremic humans: glucose transport, glucose transporters, and insulin receptors. AB - To determine the cellular basis for insulin resistance observed in patients with uremia, we investigated insulin action in vivo and in vitro using skeletal muscle obtained from patients with chronic renal failure. Uremic subjects had significantly reduced rates of insulin-stimulated glucose disposal, as determined by a 3-h intravenous glucose tolerance test and using the hyperinsulinemic euglycemic clamp technique. Hepatic glucose production was similar before (control, 76.2 +/- 6.3 vs. uremic, 74.2 +/- 6.9 mg.kg-1.min-1) and during insulin infusion at 40 mU.m-2.min-1 (control, -60.9 +/- 6.6 vs. uremic, -53.9 +/- 6.3 mg.kg-1.min-1). In incubated human skeletal muscle fiber strips, basal 2-deoxy-D glucose transport was unchanged in uremic subjects compared with controls. However, the increase in insulin-stimulated glucose transport was significantly reduced by 50% in muscles from uremic patients (P = 0.012). In partially purified insulin receptors prepared from skeletal muscle, 125I-labeled insulin binding, beta-subunit receptor autophosphorylation, and tyrosine kinase activity were all unchanged in uremic subjects. The abundance of insulin-sensitive (muscle/fat, GLUT-4) glucose transporter protein measured by Western blot using Mab 1F8 or polyclonal antisera was similar in muscles of control and uremic patients. These findings suggest that the insulin resistance observed in skeletal muscle of uremic patients cannot be attributed to defects in insulin receptor function or depletion of the GLUT-4 glucose transporter protein. An alternative step in insulin-dependent activation of the glucose transport process may be involved. PMID- 1858878 TI - Free-living energy expenditure measured by two independent techniques in pregnant and nonpregnant Gambian women. AB - Free-living energy expenditure (EE) was assessed in 37 young pregnant Gambian women at the 12th (n = 11, 53.5 +/- 1.7 kg), 24th (n = 14, 54.7 +/- 2.1 kg), and 36th (n = 12, 65.0 +/- 2.6 kg) wk of pregnancy and was compared with nonpregnant nonlactating (NPNL) control women (n = 12, 50.3 +/- 1.6 kg). The following two methods were used to assess EE: 1) the heart rate (HR) method using individual regression lines (HR vs EE) established at different activity levels in a respiration chamber and 2) the doubly labeled water (2H2(18)O) method in a subgroup of 25 pregnant and 7 control women. With the HR method the EE during the agricultural rainy season was found to be 2,408 +/- 87, 2,293 +/- 122, and 2,782 +/- 130 kcal/day at 12, 24, and 36 wk of gestation and were not significantly different from the control group (2,502 +/- 133 kcal/day). These findings were confirmed by the 2H2(18)O measurements, which failed to show any effect of pregnancy on EE. Expressed per unit body weight, the free-living EE was found to be lower (P less than 0.01 with 2H2(18)O method) at 36 wk of gestation than in the NPNL group. It is concluded that, in these Gambian women, energy-sparing mechanisms that contribute to meet the additional energy stress of gestation are operating during pregnancy (e.g., diminished spontaneous physical activity). PMID- 1858879 TI - Sympathoadrenal responses during hypoglycemia, hyperinsulinemia, and hypoxemia in the ovine fetus. AB - Interrelations of sympathoadrenal function and changes in glucose and insulin homeostasis were studied in chronically cannulated late gestation fetal sheep. Catecholamine secretory rates (based on direct adrenal sampling) and plasma concentrations were determined in the fetus during 2 h of insulin-induced hypoglycemia, during a period of hypoxemia, and during hyperinsulinemia per se (i.e., without hypoglycemia). Fetal insulin infusion (5-10 mU.kg-1.min-1) resulted in hypoglycemia and a significant rise in secretion of epinephrine but not of norepinephrine. By contrast, fetal hypoxemia caused a prompt and significant increase in adrenal secretion of both norepinephrine and epinephrine. Changes in peripheral plasma catecholamine levels were usually, but not always, qualitatively similar to those in adrenal secretion; the latter was a far more sensitive indicator of adrenal function. Hyperinsulinemia per se caused no change in adrenal secretory rates or plasma concentrations of catecholamines. Nevertheless, insulin infusion caused a fetal tachycardia even in the absence of hypoglycemia and hypoxemia, suggesting either a direct effect on the heart or stimulation of sympathetic nerves. PMID- 1858880 TI - Vagal stimulation-induced gastric damage in rats. AB - The role of the vagus nerve in the development of gastric mucosal damage was examined in urethan-anesthetized male Sprague-Dawley rats. Electrical stimulation was applied to the vagus nerves for a period of 60 min, after which macroscopic gastric damage was scored and samples of the stomach were fixed for later histological assessment. Damage scores were assigned blindly based on a 0 (normal) to 3 (severe) scale. Stimulation of vagal afferents or efferents in isolation did not result in significant damage to the gastric mucosa (P greater than 0.1). In contrast, stimulation of both intact vagus nerves resulted in significant gastric mucosal damage (mean damage score, 2.0 +/- 0.33, P less than 0.01). A second series of experiments demonstrated this gastric damage to be induced within 30-60 min; extending the stimulation period to 120 min did not worsen the gastric damage scores significantly (P greater than 0.1). In a third study, stimulation of both intact vagus nerves after paraventricular nucleus (PVN) lesion resulted in damage scores (0.33 +/- 0.17) that were significantly reduced compared with intact PVN and non-PVN-lesioned animals (P less than 0.01). These results indicate that the development of vagal stimulation-induced gastric damage requires the activation of both afferent and efferent vagal components and suggest further that such damage is dependent upon an intact PVN. PMID- 1858882 TI - Radiation and indomethacin effects on morphology, prostaglandins, and motility in dog jejunum. AB - Irradiation can have a profound effect on intestinal motor activity. Previous studies have suggested that prostaglandins may play some role in radiation induced enteritis. The present study investigated the effects of abdominal X irradiation with or without indomethacin treatment on jejunal myoelectric activity and prostaglandin synthesis by measuring the prostaglandin content of mesenteric arterial and venous plasma and in the intestinal lumen in dogs. After X-irradiation, venous concentrations and arteriovenous concentration differences of prostaglandin (PG)E2, PGF2 alpha, and 6-keto-PGF1 alpha increased markedly. The increased venous concentrations were in part attributable to increased mucosal and/or submucosal synthesis by inference from increased concentrations of these metabolites assayed from the jejunal lumen. Irradiation produced histological damage to the mucosa and submucosa and abnormalities in the migrating motor complex, jejunal slow waves, and a decrease in spike burst activity. Inhibition of prostaglandin synthesis by treating the animals with indomethacin reduced the severity of illness, the histological injury, and changes in myoelectric activity induced by irradiation. Such treatment should be evaluated further to treat patients exposed to large doses of irradiation. PMID- 1858881 TI - Mechanism of agonist-induced downregulation of muscarinic receptors in rat pancreatic acini. AB - Exposure of pancreatic acini to cholinergic agonists reduces their muscarinic acetylcholine receptor content. To investigate the mechanism of this reduction, rat pancreatic acini were cultured in the presence of carbachol and its effects on binding of [N-methyl-3H] scopolamine (NMS), which labels only cell surface receptors, and [3H]scopolamine, which also accesses intracellular receptors, were determined. Carbachol (0.1 mM) caused disappearance of 90% of binding sites for [3H]NMS and [3H]-scopolamine with half-time values of 3.9 +/- 0.4 and 5.7 +/- 0.7 h, respectively. Nocodazole and cytochalasin D, ouabain, ionophore A23187, 12-O tetradecanoylphorbol 13-acetate (TPA), bombesin, cholecystokinin octapeptide (CCK 8), secretin, and vasoactive intestinal peptide (VIP) had no effect on the carbachol-induced decrease in binding sites for either antagonist, although staurosporine and the calmodulin inhibitor W-7 each caused slight inhibition. By contrast, the lysosomotropic agents methylamine and ammonium chloride caused 80% inhibition of disappearance of binding sites for [3H]scopolamine, although they only slightly inhibited disappearance of [3H]NMS binding sites. These results implicate the endosomal/lysosomal pathway in cholinergic agonist-evoked downregulation of muscarinic receptors in the pancreatic acinar cell. PMID- 1858883 TI - Effects of hypoxia and ischemia on autoregulation in postnatal intestine. AB - Pressure-flow autoregulation was quantified within in vitro intestine from 3- and 35-day-old swine before and after lowering arterial PO2 (hypoxia) or lowering baseline blood flow by means of norepinephrine infusion (ischemia). Autoregulation was elicited by reducing arterial pressure approximately 33% from an age-appropriate baseline pressure. In 3-day-old intestine, autoregulation was unaffected by hypoxia or ischemia: vascular resistance was unchanged after pressure reduction, while Gf averaged -0.33 +/- 0.15 vs. -0.26 +/- 0.05 under control vs. hypoxic conditions, and -0.48 +/- 0.15 vs. -0.46 +/- 0.11 under control vs. ischemic conditions, respectively. In 35-day-old intestine, autoregulation was enhanced by hypoxia and ischemia. Under both experimental conditions, vasodilation was noted in response to pressure reduction: Gf averaged -0.04 +/- 0.14 vs. 0.38 +/- 0.08 under control vs. hypoxic conditions, and -0.12 +/- 0.10 vs. 0.28 +/- 0.08 under control vs. ischemic conditions, respectively. Regression analysis revealed a significant inverse linear correlation between Gf and venous PO2 in older, but not younger, subjects. Significant relationships between Gf and blood flow were not demonstrated in either group under any experimental condition. We conclude that autoregulation is enhanced within in vitro intestine from 35-, but not 3-day-old, swine during hypoxia or ischemia, and that reduction of venous PO2 is the principal factor responsible for the effect noted in older subjects. PMID- 1858884 TI - Hormonal control of avian pancreas by gastrin-releasing peptide from the proventriculus. AB - Endocrine cells in the acid-secreting part of the avian stomach, the proventriculus, contain two forms of gastrin-releasing peptide (GRP) of 27 and 6 residues, respectively. We have examined the actions of exogenous GRP-27 and GRP 6 and endogenously released GRP in the control of pancreatic secretion in urethan anesthetized turkeys. Chicken GRP-27 and the structurally related amphibian peptide bombesin were potent stimulants of fluid and protein output from the pancreas (at 6-100 pmol/kg, iv). GRP-6 had no significant effect at doses up to 1,000 times higher. A bombesin antagonist, (CH3)2-CHCO-[D-Ala24]GRP-20--26-NHCH3, inhibited the action of exogenous chicken GRP-27 but did not inhibit intravenous cholecystokinin octapeptide (CCK-8). Distension of the proventriculus with a solution of peptone produced an increase in the flow of pancreatic juice and an increase in protein output, which was not reduced by atropine. The bombesin antagonist produced a reversible inhibition of this response. A CCK-gastrin antagonist, BOC-beta-Ala-Trp-Leu-Asp-O(CH2)2- phenyl(4F), which inhibited the action of exogenous CCK, had no effect on the pancreatic response to exogenous GRP-27 or to distension of the proventriculus with peptone. We suggest that protein-rich solutions in the proventriculus release GRP, which in turn acts directly on the pancreas to stimulate enzyme secretion. PMID- 1858885 TI - Use of a modified Ussing chamber to monitor intestinal epithelial and smooth muscle functions. AB - A technique that allows the simultaneous monitoring of epithelial and smooth muscle function was developed and used to study rat small intestine in vitro. A Ussing chamber was modified so that a strain gauge force transducer could be sewn to the serosal surface of an intestinal segment clamped in the chamber. The apparatus was used to monitor short-circuit current, potential difference, and resistance across the segment, and contractions of the longitudinal layer of the muscularis externa. Both spontaneous activity and responses to the application of carbachol were recorded. Carbachol applied to the serosal side induced dose dependent increases in both short-circuit current and contractile force. The median effective doses of the two responses differed, with contractions being more sensitive to the drug. Carbachol applied to the mucosal side induced no changes in either epithelial or contractile activities. The ability of the serosal strain gauge transducer to monitor contractions faithfully was tested in an organ bath in which the gut segment was attached to an external force displacement transducer. There was a close correlation between the dose-dependent increase in force in response to carbachol measured by the serosal transducer and that measured by the force-displacement transducer (r = 0.988). Thus our technique can be used to study simultaneously epithelial and smooth muscle functions of the intestine. PMID- 1858886 TI - Adaptive regulation of brush-border amino acid transport in a chronic excluded jejunal limb. AB - We examined the alterations in brush-border glutamine transport that occurred in a surgically defunctionalized jejunal limb excluded from mucosal food contact. Dogs were surgically prepared with Roux-en-Y gastrojejunostomies to permit same intestine comparisons of glutamine transport and glutaminase activity in jejunal segments that were in incontinuity or excluded for a 6-mo period. Transport of glutamine, alanine, and glucose was measured in brush-border membrane vesicles prepared from each intestinal section; membrane marker enzymes were enriched to the same degree in incontinuity and excluded portions. The Na(+)-dependent glutamine cotransport apparent Km was the same in the excluded (779 +/- 63 microM) and incontinuity (873 +/- 105 microM) limbs. However, the Jmax for Na(+) independent glutamine transport in the incontinuity jejunum (158.7 +/- 15.7 pmol.mg protein-1.s-1) was double that in the excluded limb (71.2 +/- 4.6 pmol.mg protein-1.s-1). Na(+)-dependent carrier-mediated glutamine transport rates were lower than the Na(+)-dependent system, but Na(+)-independent kinetic parameters were not significantly different in incontinuity vs. excluded limbs (Jmax 7.9 +/- 0.6 pmol.mg protein-1.s-1; Km 140 +/- 20 microM). Similarly, the passive diffusion permeability coefficient was the same for both excluded and incontinuity jejunal limbs (22.7 +/- 0.9 nl.mg protein-1.s-1). Mucosal glutaminase enzyme activity was increased by 28% in the incontinuity limb (4.32 +/- 0.21 vs. 3.36 +/- 0.35 mumol.mg protein-1.h-1; P less than 0.02). Transport rates of alanine and glucose were also diminished in the excluded limb (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858887 TI - Effect of hibernation and jejunal bypass on mucosal structure and function. AB - Intestinal mucosal structure and function may be regulated by systemic factors associated with oral feeding, as well as local responses initiated by contact of the mucosa with food. This study compared the relative effects of these factors in an animal model that undergoes seasonal long-term fasting. Jejunal bypass operations or sham surgeries were performed on active fed ground squirrels or on squirrels that subsequently ceased feeding and hibernated. Mucosal wet weight, protein content, villus height, and surface area were reduced in jejunal segments that had minimal exposure to luminal contents (bypassed segments of active squirrels and all segments of hibernators) compared with segments exposed to the luminal stream (incontinuity and sham segments of active squirrels). When normalized to mucosal weight, transepithelial absorption of 3-O-methylglucose and alanine-dependent sodium flux were greater in jejunal segments with minimal exposure to luminal nutrients. Altered structure in bypassed segments of active and hibernating squirrels paralleled changes in functional parameters despite the presence of different systemic factors in the two groups. Thus, in this animal model, contact of the mucosa with food, and not systemic factors associated with oral feeding, is the primary factor maintaining mucosal mass. The absence of mucosal contact with nutrients enhances specific absorptive function by mechanisms that have yet to be determined. PMID- 1858888 TI - Reduced glutathione protects cultured gastric mucosal cells from suckling rats against acid. AB - We examined the role of reduced glutathione as a defense mechanism against acid induced gastric mucosal cell damage in vitro. Cellular stores of reduced glutathione were depleted by reaction with diethyl maleate (DEM) or 1-chloro-2,4 dinitrobenzene (CDNB) and increased by reaction with L-cysteine. Depletion of cellular glutathione by reaction with DEM or CDNB potentiated gastric mucosal cell lysis by acid. Increase of cellular glutathione by L-cysteine decreased cell lysis by acid. Altering the cellular reduced-to-oxidized glutathione ratio by tert-butyl hydroperoxide or diamide increased cellular susceptibility to acid. Reduced glutathione is essential for glutathione peroxidase to catalyze hydrogen peroxide. We further studied whether oxygen free radicals were involved in the pathogenesis of acid-induced gastric mucosal injury in vitro. Neither superoxide dismutase, catalase, nor dimethyl sulfoxide decreased acid-induced gastric mucosal cell damage. We conclude that reduced glutathione plays an important role as a defense mechanism against acid-induced injury in cultured rat gastric mucosal cells. Production of oxygen radical in response to acid exposure may occur intracellularly, since exogenous oxygen radical scavengers, which do not gain access to the interior of cells, had no protective effect. Reduced glutathione might protect gastric mucosal cells by mechanisms other than the elimination of oxygen free radicals. PMID- 1858889 TI - Electrical slow-wave activity from the circular layer of cat terminal antrum. AB - Intracellular recording techniques were used to characterize the electrical slow wave activity through the thickness of the circular muscle layer of the cat terminal antrum. Muscle strips were pinned out in cross section to the floor of a recording chamber perfused with Krebs buffer. Circular muscle cells from the myenteric to the submucosal border then were impaled with 20- to 40-M omega glass microelectrodes, and slow-wave activity was recorded. Slow waves from the myenteric side of the circular layer consisted of an upstroke depolarization, a prominent plateau phase, and a downstroke repolarization. Slow-wave characteristics for cells along the myenteric border were Em, -74.2 +/- 1.3 mV; duration, 5.3 +/- 0.5 s; upstroke amplitude, 29.4 +/- 3.4 mV; upstroke velocity, 0.20 +/- 0.03 V/s; and frequency, 5.8 +/- 0.5/min. Slow waves from muscle cells along the submucosal side of the preparation lacked a discernible plateau phase. Slow waves from submucosal border cells had the following characteristics: Em, 80.4 +/- 1.4 mV (P less than 0.01); duration, 3.5 +/- 0.4 s (P less than 0.01); upstroke amplitude, 44.0 +/- 2.4 mV (P less than 0.01); upstroke velocity, 0.56 +/- 0.06 V/s (P less than 0.01); and frequency, 4.2 +/- 0.4/min (P less than 0.05). Slow waves were not affected by 10(-7)M tetrodotoxin and 10(-6)M atropine or by removal of the longitudinal muscle layer. Slow-wave activity within each region was maintained after dissecting the circular layer into submucosal and myenteric segments. The results suggest that two distinct slow waves exist within the circular muscle layer of the cat terminal antrum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858890 TI - Hepatic transport of a fluorescent stearate derivative: electrochemical driving forces in intact rat liver. AB - We determined the effect of varying the transmembrane Na+ electrochemical gradient on extraction of a fluorescent derivative of stearate, 12-N-methyl-7 nitrobenzo-2-oxa-1,3,-diazol-amino stearate (NBD-stearate), by the isolated perfused rat liver. Membrane potential difference (PD) of individual hepatocytes and extraction of NBD-stearate were measured simultaneously under basal conditions and during changes in PD induced by perfusate ion substitutions. Under basal conditions, PD average -30 +/- 1 mV, and extraction of 10 microM NBD stearate from 1% albumin solutions averaged 0.54 +/- 0.03. Fluorescence microscopy indicated that uptake exhibited a declining portal-to-central gradient in the presence but not absence of Na+. Substitution of nitrate for Cl- hyperpolarized PD to -59 mV and increased extraction to 131% of control values. Withdrawal of nitrate and substitution of gluconate for Cl- depolarized PD to -3 and -15 mV, respectively, and decreased extraction to 63 and 73% of control values. Substitution of choline for Na+ eliminated the out-to-in Na+ gradient, depolarized PD to -16 mV, and decreased extraction to 27% of control values, an effect greater than expected for membrane depolarization alone. Uptake of NBD stearate was saturable and caused Na(+)-dependent membrane depolarization at higher concentrations (300 microM). These studies indicate that uptake of NBD stearate occurs in large part by an efficient Na(+)-dependent mechanism compatible with electrogenic Na(+)-fatty acid cotransport. PMID- 1858891 TI - Adenosine is a vasodilator in the intestinal mucosa. AB - The vasoactivity of adenosine in the intestinal mucosa of anesthetized dogs was determined using two experimental techniques. By use of the microsphere technique, infusion of adenosine (1 mumol/min ia) was found to increase significantly venous outflow and mucosal and muscularis blood flows in both jejunum (+77, +72, and +78%) and ileum (+111, +146, and +71%). In constant flow jejunal preparations, intra-arterial adenosine significantly decreased perfusion pressure (-32%), an index of vascular resistance, but did not significantly alter the blood flow distribution between the mucosa and muscularis as determined by microspheres. Thus adenosine equally dilated the mucosal and muscularis vasculatures. Using the second experimental technique, we found that local mucosal application of adenosine or non-metabolizable adenosine analogues [N6 cyclohexyladenosine or 5'-(N-ethylcarboxamido)-adenosine] dose dependently increased jejunal venous outflow. Almost all of the adenosine absorbed from the lumen was localized in the mucosal tissue, suggesting that the above hyperemia resulted from exposure of the mucosal vasculature to these compounds. The hyperemia produced by the luminal placement was not mediated by stimulation of the mucosal nerves, because the hyperemia was unaltered after treating the mucosal surface with a local anesthetic. The present results demonstrate therefore that adenosine is a vasodilator in the canine intestinal mucosa. PMID- 1858892 TI - Regulated expression of endothelin 1 in glomerular capillary endothelial cells. AB - Endothelin (ET)-1 is a powerful vasoconstrictor known to be produced and secreted by endothelial cells lining large vessels. Because ET-1 stimulates glomerular mesangial cell contraction, glomerular capillary endothelial cells (GEN), normally situated in close apposition to mesangial cells, were examined for potential ET expression and secretion. Cultured bovine GEN released ET in a time dependent fashion. ET secretion was significantly stimulated by bradykinin, an agonist known to activate phospholipase C in these cells. Preproendothelin 1 (preproET-1) mRNA levels in GEN rose in a biphasic manner on stimulation with bradykinin. The early increments (at 30 min) were not dependent on new protein synthesis, whereas the late rise (6 h after addition of bradykinin) appeared to be protein synthesis dependent. Neither early or late bradykinin-stimulated preproET-1 mRNA expression in glomerular endothelial cells was due to inhibition of mRNA breakdown. Both phases of preproET-1 mRNA expression were observed with other glomerular endothelial cell calcium-mobilizing agonists, namely thrombin, and were mimicked by the calcium ionophore ionomycin. By contrast, the protein kinase C activator phorbol myristate acetate only enhanced preproET-1 mRNA expression at 30 min and suppressed expression thereafter. It is concluded that GEN have the potential to express and secrete ET-1 in a phospholipase C-regulated fashion. Furthermore, because glomerular mesangial cells respond to this peptide, the findings raise the possibility of paracrine regulation of mesangial cell tone by glomerular endothelial cell-derived ET-1. PMID- 1858893 TI - Clonidine and PGE2 have different effects on Na+ and water transport in rat and rabbit CCD. AB - We examined the effects of prostaglandin E2 (PGE2) and the adrenergic agonist clonidine on osmotic water permeability (Pf), lumen-to-bath 22Na+ flux (Jl----b), and transepithelial voltage (VT) in isolated perfused cortical collecting ducts (CCD) from rats and rabbits. Although PGE2 inhibited arginine vasopressin (AVP) dependent Jl----b and Pf in CCDs from deoxycorticosterone (DOC)-treated and untreated rabbits, 0.1-10 microM PGE2 had no inhibitory effect on any of these transport parameters in CCDs from DOC-treated rats in presence of AVP. On the other hand, clonidine (1 microM in bathing solution) reversibly inhibited AVP dependent Pf, Jl----b, and VT in the rat CCD by 30-40%, and 0.3 microM yohimbine, a specific alpha 2-adrenoceptor antagonist, reversed these effects. However, we were unable to demonstrate any inhibitory effect of 1-10 microM clonidine on Pf, Jl----b, or VT in the rabbit CCD using a variety of protocols. These results are consistent with the pattern of inhibition of AVP-dependent adenosine 3',5'-cyclic monophosphate (cAMP) production in the rat and rabbit CCD in that PGE2 inhibits both transport and cAMP production in the rabbit but not the rat CCD, and clonidine inhibits both transport and cAMP production in the rat but not the rabbit CCD [D. Chabardes, C. Brick-Ghannam, M. Montegut, and S. Siaume-Perez, Am. J. Physiol. 255 (Renal Fluid Electrolyte Physiol. 24): F43-F48, 1988]. PMID- 1858894 TI - Adaptation of distal convoluted tubule of rats. II. Effects of chronic thiazide infusion. AB - Mammalian distal tubules adapt structurally and functionally when NaCl concentration in tubule fluid is altered chronically. These experiments were designed to test the hypothesis that chronic administration of hydrochlorothiazide (HCTZ), a drug that blocks Na and Cl uptake across apical membranes of rat distal tubule cells, would reduce intrinsic transport capacity of distal tubules and reduce the number of thiazide-sensitive transporters. Osmotic pumps were implanted into rats to deliver 3.75 mg/day HCTZ or vehicle for 10-14 days. All animals were offered a solution containing 0.8% NaCl and 0.1% KCl as drinking fluid. Free-flow micropuncture after 10-14 days indicated that Na and Cl delivery to distal tubule was not significantly different in HCTZ- and vehicle treated animals. Microperfusion in vivo with an artificial interstitial solution, with no thiazide, indicated that 10-14 days of HCTZ infusion did reduce Na transport capacity of distal tubules from 390 +/- 32 to 203 +/- 24 pmol/min (P less than 0.01). In contrast, the number of thiazide-sensitive NaCl transporters, determined as high-affinity receptors for [3H]metolazone in renal cortical membranes, was higher in HCTZ group than in controls (2.2 +/- 0.4 vs. 1.0 +/- 0.1 pmol/mg protein, P less than 0.01). These data support the hypothesis that chronic blockade of NaCl entry across apical membranes of distal tubule cells reduces NaCl transport capacity, an effect that occurs despite an increase in the number of thiazide receptors. They indicate that thiazide receptor binding studies should be interpreted in combination with direct functional measurements. PMID- 1858895 TI - Impaired renal hemodynamic response to protein feeding in dogs with experimental Fanconi syndrome. AB - These studies were designed to test the hypothesis that intact proximal tubular function is required for protein-stimulated renal vasodilation. In normal chronically instrumented conscious dogs, a meal of raw beef (10 g/kg) caused glomerular filtration rate (GFR) to increase significantly from 63 +/- 5 to 94 +/ 10 ml/min after 90 min, while plasma alpha-amino nitrogen rose from 3.9 +/- 0.2 to 6.7 +/- 0.6 mg/dl. In another group of dogs experimental Fanconi syndrome (generalized proximal tubular dysfunction) was induced with maleic acid (25 mg/kg iv, pH 7.3). GFR fell slightly but significantly from 91 +/- 18 to 66 +/- 9 ml/min after maleic acid, while Na+ excretion rose from 24 +/- 8 to 176 +/- 24 mu eq/min, alpha-amino nitrogen excretion rose from 82 +/- 40 to 148 +/- 47 micrograms/min, and glucose excretion rose from 0.2 +/- 0.1 to 6.1 +/- 1.0 mg/min. In response to a subsequent meat meal, plasma alpha-amino nitrogen rose significantly from 3.8 +/- 0.4 to 6.2 +/- 0.5 mg/dl, but GFR did not change, averaging 66 +/- 9 ml/min over the next 120 min. These results suggest that normal proximal tubular function is necessary for protein-stimulated renal vasodilation to occur. This finding is consistent with the hypothesis that the tubuloglomerular feedback mechanism may be involved in mediating the normal renal hemodynamic response to protein feeding. PMID- 1858896 TI - ADH-induced water permeability and particle aggregates: alteration by a synthetic estrogen. AB - In the amphibian urinary bladder, the increase in water permeability induced by antidiuretic hormone (ADH) is accompanied by the appearance of apical intramembrane particle (IMP) aggregates that are believed to contain specific channels for water. In a previous work, we have shown that 3,3' diallyldiethylstilbestrol (DADES), a synthetic estrogen which is a blocker of the glucose transporter, also inhibits the hydrosmotic response to ADH in the bladder. Our aim in the present study was to analyze the alterations of the membrane fine structure further and to correlate them with the water permeability changes. The results point to a selective inhibition of the ADH-induced net water flow, probably due to an interference with one of the last steps of the response to the hormone. This inhibition is associated with an increase in the density of the apical IMP aggregates, which are thus probably not operational. The resting net water flow is not inhibited and, surprisingly, typical IMP aggregates are frequently observed in the apical membrane after DADES treatment. The compound also induces the appearance of unusual loose IMP clusters that can only be seen on the apical membrane of the granular cells and that share several ultrastructural similarities with the ADH-induced aggregates. These results suggest that 1) apical DADES treatment stimulates the insertion of IMP aggregates in the apical membrane of the urinary bladder and 2) DADES inhibits the ADH induced water flow by interfering with the aggregates and thus probably by blocking the specific water channels. PMID- 1858897 TI - Changes in NMR-visible kidney cell phosphate with age and diet: relationship to phosphate transport. AB - To test the hypothesis that growth and dietary Pi affect the intracellular concentration of Pi ([Pi]i) as well as its renal reabsorption, we measured nuclear magnetic resonance (NMR)-visible [Pi]i in isolated perfused kidneys of less than 1- and greater than 4-wk-old guinea pigs fed various amounts of Pi. Changes in [Pi]i were correlated with those in fractional Pi reabsorption (FRPi) in vivo and in capacity (Vmax) for Na(+)-Pi cotransport in microvilli derived from animals of similar age and fed the same diets. In animals fed normal (0.76% Pi) diet, [Pi]i was lower (0.91 +/- 0.14 vs. 1.85 +/- 0.23 mM, P less than 0.05), whereas FRPi was higher (0.90 +/- 0.02 vs. 0.70 +/- 0.03, P less than 0.01) in less than 1- than in greater than 4-wk-old guinea pigs. Pi deprivation decreased [Pi]i in mature animals to 0.74 +/- 0.29 mM, P less than 0.05, and increased FRPi to 0.99 +/- 0.01. Excess dietary Pi increased [Pi]i in immature animals to 1.67 +/- 0.56 mM, P less than 0.05, and decreased FRPi to 0.55 +/- 0.03. Diet-induced changes in [Pi]i were associated with reciprocal changes in Vmax of similar absolute magnitude in immature and mature animals. However, diets that resulted in comparable [Pi]i at the two ages were associated with higher (P less than 0.05) Vmax in less than 1- than in greater than 4-wk-old animals. The reciprocal nature of the relationship between [Pi]i and renal Pi transport indicates that [Pi]i is primarily determined by Pi efflux from the cells or Pi organification rather than Pi influx through Na(+)-Pi cotransport. Findings indicate that changes in [Pi]i with growth or diet may be a cause but cannot be the consequence of changes in abundance or maximal mobility of Na(+)-Pi cotransporters. Data also indicate that factors in addition to low [Pi]i contribute to the high Na(+)-Pi cotransport capacity observed in renal microvilli of growing animals. PMID- 1858898 TI - Cholesterol esterase in preglomerular microvessels from normal and cholesterol fed rabbits. AB - Feeding cholesterol to rabbits produces an atherosclerotic model sharing common metabolic features with the disease in humans, including the vascular lipid accumulation. In coronary vascular cells, this lipid accumulation has been associated with decreased prostacyclin (PGI2) biosynthesis and acid cholesterol esterase activity. Unlike the coronary vascular bed, renal microvasculature appears relatively resistant to atherosclerotic injury. This study examined whether renal microvessels from cholesterol-fed rabbits demonstrated similar metabolic changes in coronary vascular cells. Rabbits were fed either a 0% or 2% cholesterol diet for 1 mo. Similar to coronary vascular cells, in renal microvessels from cholesterol-fed rabbits PGI2 biosynthesis decreased and tissue concentrations of cholesterol and cholesteryl esters increased. However, unlike coronary vascular cells, renal microvascular cholesterol esterase activity increased. Light and electron microscopy revealed sporadic lipid deposits in renal microvessels from cholesterol-fed rabbits and no foam cells or occlusive lesions. In vitro addition of prostanoids to normal renal microvessels had no effect on cholesterol esterase activity. It is inviting to speculate that the increased acid cholesterol esterase activity in renal microvessels from cholesterol-fed rabbits protected them from developing extensive microvascular lesions. These biochemical events may explain the relative resistance of human renal microvessels to the development of occlusive atherosclerotic microvascular lesions. PMID- 1858899 TI - Dynamics of intrarenal pressures and glomerular filtration rate after acetazolamide. AB - The dynamics of intrarenal pressures, early distal tubular fluid conductivity (EDC), and renal flood flow (RBF) were studied in rats given acetazolamide (ACZ), an inhibitor of proximal reabsorption. Glomerular filtration rate (GFR) and end proximal flow were estimated by clearances of 51Cr-EDTA and lithium. Proximal tubular pressure (Pprox) increased initially by 1.7 +/- 0.1 mmHg after ACZ, causing a decrease in the hydrostatic pressure difference across the glomerular membrane (delta P). EDC increased, and then RBF, glomerular capillary pressure (Pgc), Pprox, and star vessel pressures (Psv) dropped as a result of afferent vasoconstriction. Pprox decreased less than Pgc, resulting in a further decrease in delta P, which after 25-30 s reached a constant level 3-4 mmHg below control. After a transient increase the pressures declined to a new steady state, in which Pprox was equal to control, Pgc was decreased, and distal tubular pressure, end proximal flow, and EDC were increased. GFR was depressed by 29%. The results indicate that the tubuloglomerular feedback mechanism controls Pgc and Pprox by afferent vasoconstriction, as well as efferent vasodilation. The data also indicate that proximal reabsorption rate is important in determining the changes in delta P by its effect on Pprox at least in the early transient phase. PMID- 1858900 TI - Myo-inositol and betaine transporters regulated by tonicity are basolateral in MDCK cells. AB - Myo-inositol and glycinebetaine are compatible osmolytes accumulated in the renal medulla and in MDCK cells cultured in hypertonic media. Both osmolytes are taken up by MDCK cells on Na-coupled transporters. The maximal velocity (Vmax) of both cotransporters is increased by culture in hypertonic medium. When hypertonic MDCK cells are shifted to isotonic medium there is a large transient efflux of osmolytes. To determine the polarity of the cotransporters and the transient efflux, we grew MDCK cells on a porous support to assay transport separately at their apical and basolateral surfaces. In hypertonic cells, basolateral uptake of both osmolytes was 1) more than 10-fold apical uptake, 2) greater than 96% Na dependent, 3) 25- (myo-inositol) and 16-fold (glycinebetaine) uptake in isotonic cells, reaching a maximum 24 h after the switch to hypertonic medium. When medium osmolarity was decreased from hypertonic to isotonic, myo-inositol uptake reversed to the isotonic level within 1 day; glycinebetaine uptake decreased more slowly. When medium osmolarity was decreased from hypertonic to isotonic, there was a large transient increase in basolateral efflux of both osmolytes. PMID- 1858901 TI - Photon-counting microcolorimeter with 40-nl cuvette. AB - A colorimeter with a 40-nl cuvette has been constructed. The wall of standard capillary glass was perforated to produce a sample injection port. A section of the capillary glass was drawn to a length of 1/2 cm and 80 microns ID by heating on a microforge. This produced a cuvette volume of approximately 40 nl. Two fiber optic filaments, 80 microns in diameter, were fixed into the cuvette to transmit and receive light from the sample. The output of the colorimeter was measured with a microscope photon-counting detection assembly. It has been shown that the colorimeter enables a reduction of the plasma volume requirements of the Lowry microprotein assay from several nanoliters to 60 pl. The linearity and reproducibility of the microcolorimeter when used with the Lowry assay has been verified. The colorimeter output is several orders of magnitude above the lower limit of detection of the photon counter. PMID- 1858902 TI - Interaction of trichlormethiazide or amiloride with PTH in stimulating Ca2+ absorption in rabbit CNT. AB - To determine the renal tubular site and mechanism of the anticalciuric effects of trichloromethiazide (TCM) and amiloride, we studied the effects of these diuretics on net Ca2+ absorption (JCa) in isolated rabbit connecting tubules (CNT) and cortical collecting ducts (CCD). TCM (100 microM) in the lumen increased JCa in the CNT without affecting lumen-negative transepithelial voltage (VT). This effect was dependent on the amount of parathyroid hormone (PTH, 0.1 or 1 nM) in the bath. TCM had no detectable effect on JCa in the absence of PTH. Addition of 100 microM ouabain to the bath decreased PTH-stimulated JCa and abolished the TCM-stimulated JCa. Elimination of Na+ from the lumen increased PTH stimulated JCa. Under this condition the ability of TCM to increase JCa was abolished, suggesting that the inhibition of Na+ entry from the lumen with TCM may account for the increase in PTH-stimulated JCa. Elimination of Na+ from the bath in the presence of PTH decreased JCa and abolished the stimulatory effect of TCM on JCa in the presence of PTH. Changes in VT caused by amiloride may not account for the increase in JCa, because JCa was not changed when VT was deflected to more positive direction by increasing bath K+ from 5 to 15 mM. Neither TCM nor amiloride affected JCa in the CCD. From these observations, we speculate that the inhibition of Na+ entry across the apical cell membrane by either thiazides or amiloride may stimulate PTH-induced JCa. The intact Na(+) Ca2+ antiporter in the basolateral cell membrane is essential for the anticalciuric effect of thiazides and amiloride. PMID- 1858903 TI - Norepinephrine spillover faithfully reflects renal sympathetic nerve activity in conscious rabbits. AB - The relationship between directly recorded renal sympathetic nerve activity (RSNA) and simultaneous renal norepinephrine (NE) spillover rate across the kidney at rest and in response to changes in mean arterial pressure (MAP) was examined in six conscious rabbits. Integrated RSNA and renal NE spillover rate at rest were 5.1 +/- 1.1 microV/s and 20.8 +/- 3.0 ng/min, respectively. Sodium nitroprusside infusions at 10 and 20 microgram.kg-1.min-1 significantly increased RSNA by 42 +/- 14 and 84 +/- 14% and renal NE spillover rate 39 +/- 22 and 107 +/ 22% in response to falls in MAP of 15 +/- 2 and 21 +/- 2 mmHg (19 and 27%), respectively. During phenylephrine infusion at 8 micrograms.kg-1.min-1, RSNA and renal NE spillover rate significantly decreased by 65 +/- 14 and 67 +/- 16%, respectively, in response to a 15 +/- 2 mmHg (19%) rise in MAP. There was a highly significant positive correlation between changes in directly recorded RSNA and changes in renal NE spillover rate (r = 0.81, P less than 0.01). The ratio of renal to total NE spillover rate at rest was 0.44 +/- 0.06. This ratio was decreased during both sympathetic stimulation (0.30 +/- 0.04) and inhibition (0.26 +/- 0.06). This study indicates that the measurement of renal NE spillover rate is a useful reliable method for detecting the changes in RSNA and its relative contribution to overall sympathetic nerve activity in response to physiological stimuli in conscious rabbits. PMID- 1858904 TI - Role of cytoskeleton in isotonic cell volume control of rabbit proximal tubules. AB - Stability of mammalian cell volume depends primarily on the sodium pump. When active cation transport of rabbit renal proximal tubules is blocked by ouabain, cells swell, but their size is limited by residual volume control mechanisms. This "ouabain-resistant" volume control is not an active process, as it operates in the presence of cyanide and dinitrophenol and in the absence of exogenous energy. Nevertheless, it remains incompletely explained by known transmembrane oncotic and hydrostatic forces. We tested the hypothesis that the cytoskeleton contributes to isotonic cell volume control. Isolated, collapsed rabbit proximal convoluted tubules (PCT) were crimped at both ends with micropipettes and had their volume assessed optically. PCT in ouabain (1 mM) swelled to 1.40 above control with protein, 1.62 without protein, and 1.89 with the cytoskeleton inhibitors vincristine (5 microM) and cytochalasin B (50 microM) and without protein. Tubulozole-C and cytochalasin D gave similar results. A hydrostatic pressure of 50 cmH2O increased tubule volume to 1.93 before the tubule basement membrane (TBM) prevented further volume increase. We conclude that volume of renal tubule cells in ouabain is limited partly by external protein, but primarily by the cytoskeleton. The TBM prevents massive swelling and tubule disaggregation. PMID- 1858905 TI - Effects of dopamine-receptor antagonists and renal denervation on amino acid induced hyperfiltration. AB - The mechanism whereby an infusion of amino acids (AA) leads to increments in glomerular filtration rate (GFR) and renal plasma flow (RPF) is incompletely understood. Dopamine (DA) is a catecholamine in which known actions at low doses include the ability to increase both GFR and RPF. Furthermore, urinary DA excretion has been shown to be augmented after an oral protein load. We therefore studied the renal hemodynamic response to intravenous infusion of a 10% mixed AA solution in anesthetized euvolemic Wistar-Furth rats in the presence or absence of specific DA1 [Sch 23390 (SCH)] and DA2 [S-sulpiride (S-SP)] receptor antagonists. Infusion of AA in vehicle-pretreated rats resulted in a 28 +/- 8% increase in GFR and a 29 +/- 6% increase in effective ERPF over baseline values. Administration of AA in the presence of SCH also resulted in elevations in both GFR and ERPF by 23 +/- 3% and 26 +/- 6%, respectively. In contrast, when AA were given in the presence of S-SP, the rise in both GFR and ERPF was completely prevented. To examine whether the AA-induced hyperfiltration was due to DA release from renal nerves or enhanced renal tubule DA synthesis, we administered AA to rats in which the left kidney had been chronically denervated while the right kidney remained intact. Infusion of AA led to significant increments in GFR (33 +/- 4%) and ERPF (34 +/- 7%) only in the intact control kidney, whereas GFR and ERPF remained unaltered in the denervated kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858906 TI - Alteration in surface ion composition of cultured bone during metabolic, but not respiratory, acidosis. AB - Acidosis produced by a fall in [HCO3-] (metabolic acidosis, Met) produces greater Ca efflux from cultured bone than that produced by a rise in PCO2 (respiratory acidosis, Resp). To compare the effects of Met and Resp on bone surface ion composition we measured the surface abundance of 40Ca, 23Na, and 39K in cultured bone with a scanning ion microprobe utilizing secondary-ion mass spectrometry. Neonatal mouse calvariae were incubated for 24 h in medium simulating either Met (pH = 7.193 +/- 0.034, [HCO3-] = 15.1 +/- 1.4 meq/l), Resp (pH = 7.153 +/- 0.014, PCO2 = 85.4 +/- 1.2 mmHg) or normal physiological (Ctl; pH = 7.484 +/- 0.009, [HCO3-] = 29.7 +/- 0.7, PCO2 = 39.6 +/- 0.3) conditions. The surface of Ctl at 2 nm depth is rich in Na and K relative to Ca (Na/Ca = 25.6, K/Ca = 12.0, ratios of counts/s of secondary ions). Compared with Ctl, Met produced a sharp fall in both Na/Ca (6.5, P less than 0.01) and K/Ca (4.6, P less than 0.01), whereas Resp did not alter Na/Ca (23.8) or K/Ca (15.0). Ca efflux was greater in Met (873 +/- 54 nmol.bone-1.24 h-1) than in Resp (546 +/- 71 nmol.bone-1.24 h-1, P less than 0.01), which was greater than that in Ctl (315 +/- 49 nmol.bone-1.24 h-1, P less than 0.01 vs. Met and vs. Resp).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858907 TI - Postnatal maturation of rabbit renal collecting duct. II. Morphological observations. AB - The renal collecting duct exhibits cellular heterogeneity. An ultrastructural analysis of this nephron segment during maturation has been performed to determine morphological characteristics of developing principal and intercalated cells (IC). Apical surface features and cytoplasmic ultrastructure were best revealed by scanning electron microscopy and by transmission electron microscopy, respectively. Morphological maturity was assessed by comparing measurements of apical perimeter, vesicular profiles, and mitochondrial volume percent. In mature cortical collecting duct (CCD), approximately 30% of total cells were rich in mitochondria and generally dark in matrix staining, i.e., IC. Most IC in outer cortex were microvillated, whereas in inner cortex most IC were microplicated with interspersed microvilli. Only approximately 16% of cells in outer medullary collecting duct (OMCD, outer stripe) were IC, with light cytoplasm and large protruding apical surfaces covered exclusively with microplicae. Neonatal CCDs showed no IC in outer cortex; a single type of principal-like cell was found in outer cortical region. Neonatal IC in both CCDs and OMCDs showed smaller apical perimeters, vesicular volumes, and mitochondrial volume percents than did mature IC. Whereas the number of cortical IC was reduced in the newborn, IC were present in mature numbers in OMCD and appeared relatively more mature than did IC of CCD. Some (approximately 10%) of IC in neonatal CCD did not show an identifiable apical surface pattern. Principal cells from both newborn CCD and OMCD were also morphometrically immature. It is clear that the neonatal collecting duct undergoes postnatal proliferation and differentiation. PMID- 1858908 TI - Postnatal changes in heart mitochondrial calcium and energy metabolism. AB - The newborn mammalian heart has less functional capacity compared with the adult, yet newborn myocardial mitochondrial respiratory activity is the same or exceeds that of adult. This study was aimed at determining the temporal changes in newborn rabbit heart mitochondrial energy-linked Ca2+ transport during early postnatal development. At birth, substrate-supported Ca2+ uptake is twice that of adult and declines toward adult rates during the first 14 days. Both NADH- and succinate-linked respiration are equivalent to adult values at birth, increase transiently during the first 7 days, and then decline toward adult. Newborn heart mitochondrial preparations exhibit the same membrane potential (delta psi) values during Ca2+ uptake and have comparable rates of Na(+)-induced Ca2+ efflux as adult. Creatine kinase (CK) activity is very low in 1- to 7-day-old newborn mitochondria and increases rapidly toward adult values after 10 days of age. The decreasing rates of Ca2+ uptake do not appear to be related to respiratory activity, membrane potential, or increased cycling of Ca2+ but rather to a direct effect on the mitochondrial Ca2+ uniporter. Preliminary studies indicate changes in mitochondrial membrane phospholipids during early development that may be related to the increasing CK activity and decreasing Ca2+ uptake and respiration. We postulate that mitochondrial membrane lipid changes in early postnatal development may be the causative factor underlying these changes in functional activity. PMID- 1858909 TI - Intracranial pressures and O2 extraction in conscious sheep during 72 h of hypoxia. AB - High-altitude cerebral edema may occur within several days after a rapid ascent to altitude. However, the mechanisms that produce this potentially lethal condition are unclear. This experiment assessed systemic arterial and intracranial pressures (n = 22) and cerebral blood flow per unit cerebral O2 consumption (Qc/cVo2) and cerebral O2 extraction fraction (cEo2) (n = 9) in conscious sheep before and during 72 h of normobaric hypoxia (arterial O2 tension approximately 40 mmHg, oxygen saturation in arterial blood approximately 50%). Qc/cVo2 and cEo2 were calculated from systemic arterial and cerebral venous O2 contents. Wet-to-dry brain weight ratios were calculated during normoxia (n = 4) or after 72 h of hypoxia (n = 5) in additional sheep. Intracranial pressures did not change during hypoxia (+ 1.3 to +1.8 mmHg, P = 1.0); however, estimated intracranial capillary hydrostatic pressure may have increased 1-20 mmHg depending on the arterial-to-downstream resistance ratio. During the 72 h of hypoxia, Qc/cVO2 doubled (P = 0.02) and cEo2 tended to decrease (5% absolute, P = 1.0). Regional wet-to-dry brain weight ratios after 72 h of hypoxia were 4-13% greater than their respective ratios during normoxia (0.001 less than P less than or equal to 0.05); indirect evidence suggests that this increased brain water content was extravascular. The sheep may be an appropriate model for the further study of high-altitude cerebral edema. PMID- 1858910 TI - Variation in local cerebral blood flow response to high-dose pentobarbital sodium in the rat. AB - Microvascular bed structure and functions are known to vary throughout the brain. Microvascular responses to high doses of pentobarbital sodium might therefore differ among brain areas. This possibility was examined by measuring local cerebral blood flow (LCBF) with [14C]iodoantipyrine in 52 brain areas at 5, 10, 25, and 60 min after intraperitoneal administration of pentobarbital (50 mg/kg). From 5 to 60 min, LCBF was significantly lowered in 17 of 25 forebrain gray matter areas but in only 1 of 18 hindbrain gray matter structures, the pontine nuclei. Smaller, shorter duration lowering of LCBF was also observed in ten other brain areas. In both control and treated rats, LCBF was found to vary within individual brain structures. The pattern of these LCBF variations was columnar in the cerebral cortex and the hippocampus but was patchy in the caudate-putamen, thalamus, and inferior colliculus. These results indicate that pentobarbital anesthesia more strongly alters LCBF in the forebrain than in the hindbrain and produces different patterns of changes in LCBF than in local cerebral glucose utilization, which was measured with 2-deoxyglucose in a companion study. PMID- 1858911 TI - Systolic and diastolic dysfunction of the left ventricle induced by dietary taurine deficiency in cats. AB - Isovolumic left ventricular (LV) preparations were used to assess myocardial failure associated with dietary taurine deficiency in cats. Adult female cats (n = 12) were fed a purified diet devoid of taurine for 6-8 mo. Six of the cats received 1,000 mg of crystalline taurine orally once daily. The remaining six cats were not provided taurine replacement. Compared with control preparations, hearts isolated from taurine-deficient cats generated significantly lower values for developed LV systolic pressure (107 +/- 6 vs. 66 +/- 15 mmHg; P less than 0.05), maximal rate of LV pressure rise (+dP/dtmax; 1,103 +/- 38 vs. 718 +/- 172 mmHg/s; P less than 0.05), and fall (-dP/dtmax; 930 +/- 46 vs. 587 +/- 129 mmHg/s; P less than 0.05). LV function curves generated by hearts from taurine deficient cats were shifted downward and to the right of control curves, demonstrating inotropic depression. In addition, end-diastolic pressure-volume (compliance) relationships in hearts from taurine-deficient cats were shifted downward and to the right of controls in the direction of increased chamber compliance or distensibility. Ten millimolar taurine significantly improved inotropic indexes only in hearts from taurine-deficient cats but failed to affect diastolic compliance. Myocardial contractile dysfunction and LV chamber dilatation in hearts from taurine-deficient cats verify a causal association between dietary deficiency of this amino acid and dilated cardiomyopathy in this species. PMID- 1858912 TI - EDRF released from microvascular endothelial cells dilates arterioles in vivo. AB - Microvascular endothelial cells (MECs) from rat epididymal fat pad were isolated and cultured in vitro on Cytodex 3 microcarrier beads. In Krebs-suffused cremaster muscle of pentobarbital-anesthetized rats arteriolar diameters (mean control diam 20.9 +/- 0.9 micron) were measured using image shearing video microscopy. Two lines of suffusate (1.5 ml/min each) were established; one contained a column of microcarrier beads only (no cells in line; NC) the other contained a 1-ml column of MECs grown on beads (through cells; TC). The muscle preparation and the MECs were first treated with indomethacin (Indo; 28 microM). Indo treatment blocked arteriolar dilation to A23187 (1 microM) and arachidonic acid (AA; 0.25 microM) administered into the NC line. A 4.0 +/- 0.6 micron increase in arteriolar diameter was observed, however, when A23187 (but not AA) was infused through the TC line containing Indotreated MECs on beads. The A23187 elicited dilation was abolished by the introduction of NG-monomethyl-L-arginine (L-NMMA; 200 microM) into the TC line. Administration of atropine (2 microM) onto the cremaster muscle via the NC line inhibited the dilations in response to acetylcholine (ACh; 2.7 microM) given through the NC line. Infusion of ACh through the TC line onto the atropine-treated cremaster muscle, however, elicited a 5.8 +/- 1.3 micron increase in arteriolar diameter, a response that was blocked by prior administration of L-NMMA into the TC line. Arteriolar dilation induced by adenosine (0.5 microM) or sodium nitroprusside (0.5 microM) applied via the NC or TC line was unaffected by L-NMMA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858913 TI - Enhanced renal PGE2 in hypertensives with increased red cell Na(+)-Li+ countertransport. AB - In this study, maximal velocities of Na(+)-Li+ countertransport were measured in red blood cells of 50 untreated essential hypertensives and 30 normotensive controls. In addition, urinary excretion of renal prostaglandins (PG) and plasma renin activity (PRA) was measured in each subject. Maximal velocity of Na(+)-Li+ countertransport was above the upper limit in controls of 525 mumol.l cell-1.h-1 in seven patients and was normal in the remaining patients. Patients with increased countertransport did not differ significantly from controls and from patients with normal countertransport with regard to urinary excretion of 6-keto PGF1 alpha (the stable metabolite of prostacyclin) and thromboxane B2 (TxB2) (the stable metabolite of thromboxane A2). In contrast, mean values of PGE2 were significantly higher (P less than 0.01) in patients with increased countertransport (411 +/- 39 pg/min) compared with patients with normal countertransport (181 +/- 15 pg/min) and controls (146 +/- 13 pg/min). In addition, six patients with increased countertransport exhibited urinary levels of PGE2 higher than the upper limit in controls. Hypertensives with increased countertransport showed enhanced PRA when compared with the remaining patients (2.96 +/- 0.50 vs. 1.30 +/- 0.52 ng.ml-1.h-1, P less than 0.05) and with controls (1.86 +/- 0.08 ng.ml-1.h-1, P less than 0.05). Finally, the relationship between PGE2 and PRA was found to be significant in patients with increased countertransport (r = 0.776, P less than 0.05). These results indicate that renal synthesis of PGE2 is enhanced in essential hypertensives with increased Na(+)-Li+ countertransport activity and hyperreninemia. PMID- 1858914 TI - Tachycardia-induced cardiomyopathy: effects on blood flow and capillary structure. AB - Chronic supraventricular tachycardia (SVT) causes a dilated cardiomyopathy. A potential factor contributing to the development of SVT-induced cardiomyopathy is abnormal myocardial blood flow (MBF). The purpose of this study was to relate changes in left ventricular (LV) function, MBF, and capillary structure with the development of SVT-induced cardiomyopathy. LV function and MBF were measured in two groups of conscious pigs: sham control (CON; n = 8) and after 3 wk of atrial pacing (SVT; 240 beats/min; n = 8) using echocardiography-catheterization and microspheres. Measurements were made under three states: 1) at rest with a basal heart rate, 2) during rapid atrial pacing (240 beats/min), and 3) during adenosine infusion (1.5 microM.kg-1.min-1) without pacing. LV capillary density, diameter, wall thickness, and capillary-myocyte distance were measured in four additional pigs from each group. LV fractional shortening was lower, and left atrial pressure was significantly higher in the SVT group compared with CON at rest, during pacing, and with adenosine (P less than 0.05). In the CON group, average LV-MBF at rest was 2.0 +/- 0.2 ml.min-1.g-1, increased with pacing to 3.0 +/- 0.2 ml.min-1.g-1 (P less than 0.05), and increased further with adenosine to 4.1 +/- 0.3 ml.min-1.g-1 (P less than 0.05). In all states, SVT LV-MBF was significantly reduced vs. CON (P less than 0.05); SVT LV-MBF was 0.8 +/- 0.2 ml.min-1.g-1 at rest, increased to 1.3 +/- 0.3 ml.min-1.g-1 with rapid pacing (P less than 0.05), and remained unchanged during adenosine (1.3 +/- 0.4 ml.min-1.g 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858915 TI - Flow modulation of agonist (ATP)-response (Ca2+) coupling in vascular endothelial cells. AB - ATP-induced increases of intracellular calcium concentration ([Ca2+]i) were measured as a function of flow rate in single cell recordings within a confluent endothelial cell monolayer. Although flow and its associated shear stress did not per se significantly alter basal [Ca2+]i, ATP-induced [Ca2+]i was exquisitely sensitive to flow. Step increases of flow in the presence of ATP triggered large [Ca2+]i transients that slowly (60-150 s) returned to basal values. ATP releasable [Ca2+]i was mobilized from intracellular stores, as well as obtained from the extracellular medium. Since potent ectonucleotidases on the cell surface are expected to influence local ATP concentrations, experiments were repeated using the poorly hydrolyzable ATP analogue beta, gamma-methyleneadenosine 5' triphosphate (AMP-PCP). Comparison between ATP and AMP-PCP responses suggested that flow regulates the mass transport of agonist to the endothelial cell surface by overcoming the local effects of degradative enzymes. An additional, quite different phenomenon of flow-mediated [Ca2+]i regulation in endothelial cells was observed when [Ca2+]i oscillations induced by AMP-PCP in the absence of flow were shown to be reversibly inhibited by step increases in flow. These results imply that the effectiveness of local or systemic agonists in stimulating endothelial transduction will vary with flow rates. Regional variations in hemodynamic shear stresses associated with altered flow patterns throughout the arterial system are predicted to result in large variations of vessel wall responsiveness to physiological and pathological agonists. PMID- 1858916 TI - Agents that modify EDRF formation alter antiplatelet properties of brain arteriolar endothelium in vivo. AB - In the presence of circulating Evans blue a helium-neon laser injures the endothelium of brain surface arterioles in situ. The injury is known to selectively eliminate endothelium-dependent responses. The present study documents in mice the fact that such endothelial sites become selectively attractive to passing platelets that have been activated as a result of more severe injury upstream. We then test the hypothesis that the "capture" of platelets at the downstream site is due to loss of "classical" endothelial dependent relaxing factor of acetylcholine (EDRFACh) at that site. EDRFACh is known to inhibit platelet adhesion/aggregation and is synthesized from L arginine. We show that agents that would either enhance or reduce the synthesis of local EDRFACh reduce or increase the incidence of capture as predicted by the hypothesis. Thus NG-monomethyl-L-arginine (L-NMMA) and arginase that would reduce synthesis of EDRFACh enhanced platelet capture. L-Arginine, which would enhance synthesis of EDRFACh, inhibited platelet capture. In addition, L-NMMA and arginase enhanced platelet aggregation over the more severely damaged site upstream from the site of capture. Ex vivo studies of platelets harvested from treated mice showed that the platelets themselves were unaffected by the treatments that, except for arginase given intravenously, all involved topical application of the tested drugs. PMID- 1858917 TI - Effect of chronic verapamil treatment on ventricular function and growth in chick embryos. AB - Adjustment of myocardial mass to work load is a fundamental characteristic of the heart. We studied the effect of verapamil, a calcium channel blocker, on growth and function of chick embryonic ventricle. We treated stage 18 chick embryos with verapamil delivered to the extraembryonic vascular bed by a miniosmotic pump and compared them with saline-treated control and untreated embryos. At stages 24, 27, and 29, we measured ventricular pressure and dP/dt by a servo-null system, dorsal aortic stroke volume and dV/dt by pulsed-Doppler, and ventricular and embryo wet weights. Mean myocyte profile area was measured by digital planimetry technique, and cell growth response by DNA and protein assay. Verapamil treatment decreased ventricular pressure in experimental (P less than 0.05) compared with saline control and normal embryos; at stage 27, 1.59 +/- 0.21 vs. 2.17 +/- 0.05 and 2.35 +/- 0.08 (SE) mmHg, respectively. Mean dorsal aortic blood flow decreased in experimental (P less than 0.05) vs. control and normal embryos; at stage 27, 0.98 +/- 0.07 vs. 1.54 +/- 0.10 and 1.56 +/- 0.07 mm3/s, respectively. Stroke volume remained the same in all experimental, normal, and control embryos except at stage 29. Ventricular weight decreased in experimental (P less than 0.05) vs. control and normal embryos; at stage 27, 1.09 +/- 0.07 vs. 1.51 +/- 0.08 and 1.54 +/- 0.11 mg, respectively. Embryo weights, myocyte size, and cytoplasmic fractional volume were similar in all groups. Morphology of ventricles was normal. DNA was lower in experimental (P less than 0.05) compared with control and normal embryos.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858918 TI - L-propionylcarnitine increases postischemic blood flow but does not affect recovery of energy charge. AB - Effects of pretreatment with L-propionylcarnitine (50 mg/kg, n = 9) or saline (n = 10) were studied in open-chest anesthetized pigs, in which ischemia was induced by decreasing left anterior descending coronary artery blood flow to 20% of baseline. After 60 min of ischemia, myocardium was reperfused for 2 h. In both groups, flow reduction abolished contractile function of the affected myocardium and caused similar decreases in ATP (by 55%) and energy charge [(ATP + 0.5ADP)/(ATP + ADP + AMP); decrease from 0.91 to 0.60], mean arterial blood pressure (by 10-24%), the maximum rate of rise in left ventricular pressure (by 26-32%), and cardiac output (by 20-30%). During reperfusion, "no-reflow" was attenuated by L-propionylcarnitine, because myocardial blood flow returned to 61 and 82% of baseline in the saline- and L-propionylcarnitine-treated animals, respectively. Cardiac output of the saline-treated animals further decreased (to 52% of baseline), and systemic vascular resistance increased from 46 +/- 3 to 61 +/- 9 mmHg.min.l-1, thereby maintaining arterial blood pressure. In L propionylcarnitine-treated pigs, cardiac output remained at 75% of baseline, and systemic vascular resistance decreased from 42 +/- 3 to 38 +/- 4 mmHg.min.l-1. In both groups, energy charge but not the ATP level of the ischemic-reperfused myocardium tended to recover, whereas the creatine phosphate level showed significantly more recovery in saline-treated animals. We conclude that L propionylcarnitine partially preserved vascular patency in ischemic-reperfused porcine myocardium but had no immediate effect on "myocardial stunning." Potential markers for long-term recovery were not affected by L propionylcarnitine. PMID- 1858919 TI - Microvascular recruitment in hamster striated muscle: role for conducted vasodilation. AB - The influence of conducted vasodilation upon arteriolar diameter and capillary red blood cell (rbc) perfusion was investigated in the cremaster muscle of male hamsters anesthetized with pentobarbital. The muscle was surgically exposed, superfused with physiological saline solution (pH 7.4; 34 degrees C), and transilluminated for observation of microvessels using intravital video microscopy. The tip (2 microns ID) of a glass micropipette filled with acetylcholine (ACh; 1.0 M) was positioned adjacent to an arteriole. Microiontophoretic delivery of an ACh stimulus (200-1,000 nA; 200-750 ms) caused vasodilation at the pipette tip, which conducted rapidly along the arteriole and decayed with distance; this was characterized by length constants of 2.1 and 2.4 mm (P greater than 0.05) for arterioles with maximal diameters of 32 +/- 2 (means +/- SE; n = 8) and 63 +/- 2 microns (n = 5), respectively. When applied to the distal end of a terminal arteriole (TA) devoid of flow, ACh triggered a dilation that was conducted proximally (greater than 1,000 microns upstream) into the parent vessel (terminal arteriole feed, TAF) containing rbc flow, thereby inducing flow into the TA; stimulation of the TAF also induced rbc flow into TA. In capillaries fed by TA, rbc flux (rbc/s) increased from zero at rest to 23 +/- 6 during the peak of the TA dilation (n = 9); calculated tube hematocrit increased from 4 +/- 2 to 28 +/- 3%. Findings demonstrate that conduction of vasodilation can coordinate vasomotor responses between terminal and parent arterioles and promote rbc delivery to capillaries supplying striated muscle fibers. PMID- 1858921 TI - Sensitivities of cardiac O2 consumption and contractility to catecholamines in dogs. AB - We studied the effects of plasma catecholamines from the adrenal gland on systolic pressure-volume area (PVA)-independent O2 consumption (VO2) and contractility index (Emax) in the left ventricle of excised cross-circulated dog hearts. PVA is a measure of the total mechanical energy of contraction. Under baseline conditions, the PVA-independent VO2 correlated with plasma catecholamine level in the hearts (r = 0.84). Plasma epinephrine and norepinephrine levels increased gradually from 0.3 and 0.4 ng/ml to 10.3 and 2.7 ng/ml on average during adrenal sympathetic nerve stimulation of support dogs. Simultaneously, Emax and PVA-independent VO2 increased by 240 +/- 127 (SD) and 75 +/- 24%. Although their increases were monotonic in a given heart, their sensitivities to catecholamines were considerably variable among hearts. However, these two sensitivities were correlated (r = 0.96) with each other in the hearts, and the interheart variation of the sensitivity of the PVA-independent VO2 to Emax (i.e., oxygen cost of Emax) was smaller. We conclude that the oxygen cost of Emax is less variable among hearts despite large interheart variations of Emax and VO2 responses to plasma catecholamines. PMID- 1858920 TI - Effects of fasting and refeeding on the proliferative response of rat aorta to injury. AB - To explore the interplay between the mitotic activity of arterial smooth muscle cells and the variations of plasma glucose and insulin concentrations, we have studied over 14 days the response of thoracic aorta to injury with a balloon catheter in rats submitted to fasting and refeeding. Animals were fasted from the day before until the third day after injury. The proliferative reaction of intima media was assessed 2, 3.5, 4, 6, 8, and 14 days after injury, comparing freely fed with fasted-refed rats. Fasting decreased plasma glucose and insulin concentrations and DNA synthesis by intima-media, whereas refeeding increased these three variables transiently. The DNA content of intima-media at any time during the response to injury and the intimal thickening on day 14 were not influenced by the sequence of fasting and refeeding, which suggests that the early decrease in DNA synthesis induced by fasting had been compensated for by the later increase in DNA synthesis induced by refeeding. In conclusion, besides hormonal influences (such as insulin), metabolic influences (such as the availability of energetic fuels) are likely to act on the proliferative response of arteries to injury. PMID- 1858922 TI - Lack of cardiovascular and vasopressin responses to human relaxin in conscious, late-pregnant rats. AB - Measurements of arterial pressure, heart rate, and plasma vasopressin were obtained in unanesthetized late-pregnant rats after administration of human relaxin (hRlx) alone or in conjunction with hemorrhage. Forty-two timed-pregnant rats were prepared with chronic femoral cannulas on the 17th day of pregnancy for measurements on the 19th day. In three separate sets of experiments, mean arterial pressure and heart rate were measured for 10 min before administration of 2 mg/kg hRlx, 100 micrograms/kg hRlx, or vehicle and for 20 h thereafter; plasma vasopressin was determined 20 min before and 3 min after administration of hRlx or vehicle and 20 min after performing a 15-ml/kg 3-min hemorrhage. Neither mean arterial pressure nor heart rate was significantly different among rats administered 2 mg/kg hRlx, 100 micrograms/kg hRlx, or vehicle. Plasma vasopressin was not significantly different among rats administered 2 mg/kg hRlx, 100 micrograms/kg hRlx, or vehicle. The decreases and subsequent compensatory changes in mean arterial pressure and heart rate after hemorrhage and the increases in plasma vasopressin were not significantly different among rats administered vehicle or hRlx. PMID- 1858923 TI - Left ventricular dysfunction induced by chronic alcohol ingestion in rats. AB - To determine whether moderate ingestion of alcohol for protracted periods of time affects normal cardiac performance and produces myocyte damage, male Fischer 344 rats at 4 mo of age were given 30% ethanol in their drinking water every day for a period of 8 mo. Experimental animals and age-matched controls were examined hemodynamically and morphometrically at 12 mo of age. Body and cardiac growth were depressed in alcoholic animals by 15 and 12%, respectively. Although left ventricular (LV) weight was reduced by 14% in alcoholic rats, no difference in right ventricular (RV) weight was noted, and consequently the ratio of RV weight to body weight increased by 12%. Systemic arterial pressures as well as LV peak systolic pressure decreased in alcoholic rats despite an unchanged heart rate. Myocardial contractility in alcoholic rats was further depressed as revealed by a significant decrease in the peak rate of ventricular pressure decay. Importantly, end-diastolic pressure was elevated 5.2-fold in the left ventricle and 2.9-fold in the right ventricle after 8 mo of ethanol consumption. LV diastolic chamber volume increased through myocardial remodeling as the longitudinal axis and transverse diameters from the base to the apex increased in experimental animals while the thickness of the LV diminished. Structural and hemodynamic alterations resulted in a 571% increase in the volume of diastolic circumferential wall stress on the left ventricle. Damage to the myocardium was increased in alcoholic animals with the volume percent of myocardial lesions increasing 342% in the wall of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858924 TI - Microvascular permeability transients due to histamine in cat limb. AB - We measured the protein solvent drag reflection coefficient (sigma f) and the capillary filtration coefficient (CFC) before and after adding 1 or 10 microM histamine to the recirculating fluid (20% plasma, remainder albumin and electrolytes, hematocrit of 1-2%) perfusing the isolated cat hindlimb preparation. Transient sigma f measurements were made at 3- to 15-min intervals after histamine using a modification of the steady-state integral-mass balance method. CFC measurements were made at approximately 10-min intervals after histamine in separate experiments. A 1 microM dose of histamine caused sigma f to fall from approximately 0.8 to approximately 0.3 in 2-3 min; sigma f then returned to control in approximately 20 min. CFC response to the 1 microM histamine was a peak increase approximately 2 times control and a return to control in approximately 40 min. A 10 microM dose caused sigma f to fall rapidly to near zero. In general, recovery was much slower than for the 1 microM dose, most of the limbs not returning to control by 40 min after histamine. CFC measurements after 10 microM histamine increased only approximately 5 times control even though sigma f was near zero at the same time. CFC remained above control for approximately 60 min. The combined sigma f and CFC data could be described quantitatively if histamine simultaneously opened both short-lived large gaps (approximately 1,000 A) and a longer-lived pathway that sieved protein like the normal pathway and if the numbers of channels of each pathway closed exponentially with 4- and 15-min time constants, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858925 TI - Effects of phorbol esters on canine coronary artery constriction and dilation in vitro. AB - The influence of protein kinase C (PKC) activation on canine coronary vasoreactivity was assessed in vitro. Activation of PKC by phorbol 12,13 dibutyrate (PDBu) or phorbol 12-myristate 13-acetate (PMA) caused slow sustained constriction of isolated coronary artery rings. PDBu was a more potent and efficacious constrictor than PMA (169 +/- 21 vs. 81 +/- 7% of maximum KCl constriction). Constriction to PDBu was reduced slightly by deendothelialization and by meclofenamate. Pretreatment with threshold concentrations of PDBu increased constriction to serotonin from 3 +/- 1 to 48 +/- 4% of maximum KCl constriction whether or not the endothelium was present but had no effect on response to the thromboxane analogue U-46619. In addition, in arteries constricted with PDBu, dilations to ADP, thrombin, acetylcholine, and sodium nitroprusside were impaired when compared with arteries constricted with U-46619. These results suggest that activation of PKC in coronary arteries 1) produces potent constriction mediated only in small part by the endothelium and by cyclooxygenase products, 2) potentiates markedly the constrictor response to serotonin by an endothelium-independent mechanism, and 3) attenuates both endothelium-dependent and endothelium-independent vasodilation. PMID- 1858927 TI - Importance of freezing time when iodoantipyrine is used for measurement of cerebral blood flow. AB - The goal of the present study was to determine effects of delay of freezing of the brain on distribution of [14C]iodoantipyrine in the brain. Blood flow to parietal cerebral cortex (CBF) and choroid plexus was measured with the indicator fractionation technique and quantitative autoradiography. After injection of iodoantipyrine, each rat was decapitated, and the head was immersed in chlorodifluoromethane (-40 degrees C). The brain was removed from the skull after it was frozen. In some rats, heads were immersed immediately after decapitation, and CBF was markedly heterogeneous. In another group, heads were frozen 3 min after decapitation. In this case, CBF was uniform in its distribution. Average CBF was similar in groups with immediate and delayed freezing (90-104 ml.min-1 x 100 g-1). In contrast, delays in freezing decreased blood flow to choroid plexus from 551 +/- 115 to 261 +/- 48 ml.min-1 x 100 g-1. Our findings indicate that immediate freezing of the brain after decapitation is necessary to prevent diffusion of iodoantipyrine from regions of high blood flow to regions of lower blood flow and underestimations of blood flow in regions with high blood flow. PMID- 1858926 TI - Contraction and relaxation of rat aorta in response to ATP. AB - Vascular responses to ATP were studied in aortic rings isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Low concentrations of ATP (10 nM to 10 microM) caused relaxation and high concentrations (0.1 mM to 10 mM) caused contraction. Both of these responses were accentuated by factors released from the endothelium. The endothelium-derived relaxing factor (EDRF) was blocked by NG-monomethyl-L-arginine (L-NMMA). This is the first time that it has been reported that ATP causes the release of an endothelium-derived contracting factor (EDCF). Its release was diminished but not completely blocked by cyclooxygenase inhibitors. Assays of muscle bath prostanoid composition indicated that ATP stimulation caused the release of prostaglandins I2 and E2 and thromboxane A2 from intact aortic rings. Evidence is presented that neither endothelin nor superoxide anion contributed to the EDCF. No difference was observed between WKY and SHRSP with regard to either the endothelial contributions to the response, or the direct action on vascular smooth muscle of ATP. High concentrations of ATP achieved intravascularly in hypoxia may cause vasospasm by release of endothelial prostanoids. PMID- 1858928 TI - Release of endothelium-derived relaxing factor is modulated both by frequency and amplitude of pulsatile flow. AB - We have dissociated the effects of frequency and amplitude of pulsatile flow on flow-induced release of endothelium-derived relaxing factor (EDRF) using cascade bioassay. Rat aortic segments were buffer perfused with a peristaltic pump at a constant mean flow rate of 9 ml/min. EDRF activity in effluent was measured by relaxation of endothelium-denuded rabbit aortic rings preconstricted by phenylephrine. Pulse frequency was varied over the range 0.1-12 Hz at a constant amplitude of 2 mmHg; pulse amplitude was varied over the range 2-16 mmHg at a constant frequency of 0.1 Hz. Relaxation of the detector vessel depended on frequency of flow through the donor; peak response occurred between 4.2 and 6 Hz and was approximately three times greater than that induced at lower or higher frequencies. In contrast, increases in pulse pressure amplitude (maximum 16 mmHg) monotonically augmented constriction of partially preconstricted detector tissue by up to 10%. Incubation of the donor vessel with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, or removal of its endothelium by rubbing, abolished both the frequency- and the amplitude-dependent effects observed in the detector tissue, indicating that these were mediated by changes in EDRF release. Increasing the amplitude of the pressure pulse also reduced mean perfusion pressure (by up to 50%), implying distension of donor vessel since mean flow rate was constant. This fall in pressure was not affected by incubation with L-NAME or removal of endothelium, indicating that it was not dependent on EDRF activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858929 TI - Effect of NG-monomethyl-L-arginine on arcade arterioles of rat spinotrapezius muscles. AB - The effect of the specific inhibitor of nitric oxide (NO) formation NG-monomethyl L-arginine (L-NMMA) on resting arteriolar diameter and on actions of both endothelium-dependent and -independent vasoactive substances was investigated using intravital microscopy in rats. The spinotrapezius muscle of anaesthetized normotensive rats was suspended in a Krebs-Henseleit bath containing tetrodotoxin (3 x 10(-7) M), indomethacin (2.8 x 10(-5) M), and propranolol (10(-6) M) to block sympathetic nerve conduction, prostacyclin formation, and beta-adrenergic receptors, respectively. Acetylcholine (ACh), nitroprusside (NP), norepinephrine (NE), phenylephrine (PE), and guanabenz (GB) were topically applied before and after superfusion of L-NMMA (10(-5) to 10(-4) M). Superfusion of L-NMMA reduced arteriolar diameter and caused dose-dependent increases in arteriolar tone. The onset of action of L-NMMA was nearly immediate. L-NMMA inhibited vasodilator responses to the endothelium-dependent vasodilator ACh but not to the endothelium independent NP. NE induced dose-related vasoconstriction that was significantly potentiated by L-NMMA. These effects were partially reversed by addition of L arginine (10(-3) M). Potentiation of vasoconstriction elicited by NE was still observed after inhibition of alpha 1-adrenoceptors with prazosin, but potentiation was abolished by the alpha 2-adrenoceptor antagonist yohimbine. L NMMA potentiated arteriolar vasoconstriction elicited by the alpha 2-adrenergic receptor agonist GB but not by the alpha 1-adrenoceptor agonist PE. These findings with L-NMMA suggest that resting diameter of arterioles is modulated by endogenous NO biosynthesis and that endothelium-dependent vasodilators act through the formation of endogenous NO to exert their action in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858930 TI - Myoglobin function and energy metabolism of isolated cardiac myocytes: effect of sodium nitrite. AB - Inactivation of intracellular myoglobin by sodium nitrite or by carbon monoxide in isolated cardiac myocytes diminishes steady-state respiratory rate and phosphocreatine concentration (PCr) by approximately 25% at nonlimiting oxygen pressures; oxidative phosphorylation and glycolysis together are insufficient to maintain ATP, and PCr falls. At concentrations required to convert myoglobin to high-spin ferric myoglobin, nitrite does not affect the respiration of isolated aerobic heart mitochondria. The creatine phosphokinase-catalyzed equilibrium between PCr and ATP is not affected by nitrite. Myoglobin inactivation reduces PCr in cells in which glycolytic ATP production is blocked by iodoacetate. However, inhibition of electron transport by rotenone does block myoglobin mediated oxygen uptake. These data suggest that functional myoglobin augments mitochondrial oxidative phosphorylation [myoglobin-mediated oxidative phosphorylation (30)]. Myoglobin itself does not cross mitochondrial membrane(s). At high oxygen pressures used here, myoglobin is everywhere saturated with oxygen, and facilitated oxygen diffusion vanishes. Oxidative phosphorylation must be augmented by some effector, such as NADH or a carrier of reducing or oxidizing equivalents that can transduce the effect of oxymyoglobin across the mitochondrial membrane(s). PMID- 1858931 TI - Vagal reflexes and survival during acute myocardial ischemia in conscious dogs with healed myocardial infarction. AB - The role of vagal tone and reflexes in the genesis of life-threatening arrhythmias was investigated in a clinically relevant animal model for sudden cardiac death. Forty-five dogs with a healed anterior myocardial infarction in which transient myocardial ischemia during exercise did not induce malignant arrhythmias were utilized for the study. They underwent a further exercise and ischemia test in which atropine (75 micrograms/kg) was injected before coronary artery occlusion. Novel occurrence of ventricular arrhythmia, or worsening of the type of arrhythmia present in the control test, occurred in 23 of 45 dogs (51%) and ventricular fibrillation occurred in 11 of 45 (24%, P = 0.001). Analysis of heart rate response to acute ischemia in the control test indicates that these 11 animals had powerful vagal reflexes during coronary artery occlusion, compared with the 34 survivors (-32 +/- 35 vs. +2 +/- 27 beats/min, P = 0.003). This study indicates that approximately 75% of animals resistant to ventricular fibrillation are characterized by weak sympathetic reflexes in response to acute myocardial ischemia. In the remaining 25% powerful vagal reflexes counteract concomitant reflex sympathetic hyperactivity, decrease heart rate, and are essential for survival. PMID- 1858932 TI - Left ventricular-arterial coupling in conscious dogs. AB - We investigated the criteria for the coupling of the left ventricle (LV) and the arterial system to maximize LV stroke work (SW) and the transformation of LV pressure-volume area (PVA) to SW. We studied eight conscious dogs that were instrumented to measure LV pressure and determine LV volume from three ultrasonically determined dimensions. The LV end-systolic pressure (PES)-volume (VES) relation was determined by caval occlusion. Its slope (EES) was compared with the arterial elastance (EA) and determined as PES per stroke volume. At rest, with intact reflexes, EES/EA was 0.96 +/- 0.20 EES/EA was varied over a wide range (0.18-2.59) by the infusion of graded doses of phenylephrine and nitroprusside before and during administration of dobutamine. Maximum LV SW, at constant inotropic state and end-diastolic volume (VED), occurred when EES/EA equaled 0.99 +/- 0.15. At constant VED and contractile state, SW was within 20% of its maximum value when EES/EA was between 0.56 and 2.29. The conversion of LV PVA to SW increased as EES/EA increased. The shape of the observed relations of the SW to EES/EA and SW/PVA to EES/EA was similar to that predicted by the theoretical consideration of LV PES-VES and arterial PES-stroke volume relations. We conclude that the LV and arterial system produce maximum SW at constant VED when EES and EA are equal; however, the relation of SW to EES/EA has a broad plateau. Only when EA greatly exceeds EES does the SW fall substantially. However, the conversion of PVA to SW increases as EES/EA increases. These observations support the utility of analyzing LV-arterial coupling in the pressure-volume plane. PMID- 1858933 TI - LV oxygen consumption and pressure-volume area: role of norepinephrine and verapamil. AB - The effect of norepinephrine or verapamil on the relationship of left ventricular (LV) myocardial oxygen consumption (MVO2) and systolic pressure-volume area (PVA) was investigated in hearts within the never-opened thorax of dogs with blocked baroreceptor reflex. LV chamber volumes and myocardial blood flow were measured using a fast computed tomography scanner. At 10 micrograms/min delivery rate of norepinephrine, MVO2 (mJ.g-1.cycle-1) equals (2.30 +/- 0.48) PVA + (20.60 +/- 4.24) (n = 11; 1 mJ.g-1.cycle-1 is equivalent to 0.563 ml O2.100 g-1.min-1 at 112 beats/min). With verapamil infusion, MVO2 equals (2.57 +/- 1.33)PVA + (10.73 +/- 3.16) (n = 17). The regression slopes did not differ (P greater than 0.25) for any of the conditions. At comparable PVA values the norepinephrine group showed an increase of MVO2 compared with the prenorephrine baseline state (P less than 0.01), and the verapamil group showed a reduction of MVO2 compared with the preverapamil baseline state (P less than 0.05). We conclude that the MVO2 to LVPVA relationship in the in situ heart, within the never-opened thorax, conveys that the oxygen-wasting effect of catecholamines is quantifiable using the shift in this relationship. PMID- 1858934 TI - Pressure-independent arteriolar rarefaction in hypertension. AB - To assess the role of pressure in the arteriolar rarefaction associated with hypertension, we studied microvascular density in a hindquarters muscle (cremaster) of rats, 8 wk after coarctation (n = 8) or sham-coarctation (n = 10) of the abdominal aorta. To document the level of arterial pressure in hindquarters vascular beds of similar rats 8-9 wk after initial surgery, we implanted femoral arterial catheters under anesthesia and, 2-5 days later, we measured conscious femoral arterial pressures in coarcted [93 +/- 4 (SE) mmHg; n = 7] and sham-coarcted (110 +/- 3 mmHg; n = 4) rats. The cremaster muscle microcirculation was examined after fixation and Microfil infusion at in vivo pressures. The density of distal third- to fourth-order arterioles was lower by 19% (P = 0.03) in coarcted (1.37 +/- 0.06 mm/mm2) than in sham-coarcted (1.69 +/- 0.11 mm/mm2) rats. We conclude that pressure-independent mechanisms are involved in the arteriolar rarefaction accompanying hypertension. PMID- 1858935 TI - Cortical blood flow changes during spreading depression in cats. AB - Changes in cortical blood flow and cerebrovascular activity occurring during and after cortical spreading depression (CSD) were studied in alpha-chloralose urethan-anesthetized cats. CSD was induced by superficial cortical pinprick, and laser-Doppler velocimetry (LDV) was used to measure cerebral blood flow (CBFLD). CSD resulted in a wave of cortical hyperemia during which there was a 215 +/- 48% peak increase in cortical blood flow that lasted for 2.7 +/- 0.4 min. This hyperemic phase was followed by prolonged cortical oligemia, with a reduction in flow of 20 +/- 4% at 1 h and 28 +/- 4% at 2 h. After CSD, cerebrovascular reactivity to the inhalation of CO2 was abolished and did not fully recover for at least 10 h. Spontaneous vasomotor activity in the cerebral microcirculation was significantly decreased after CSD, and autoregulation of cortical blood flow in response to hypotension was preserved. The abnormal cerebrovascular reactivity seen after CSD in the gyrencephalic cortex of the cat has possible significance for human migraine with aura. PMID- 1858937 TI - Effect of water restriction during growth and adulthood on kidney morphology of bobwhite quail. AB - We raised bobwhite quail (Colinus virginianus) either with unrestricted water (HYD birds) or with restricted water (DEH birds). DEH quail grew more slowly and reached lower adult body mass. Despite this, kidney mass was not different in the two groups. The number of nephrons per kidney, heterogeneity of glomerular sizes, number of medullary cones per kidney, and lengths of medullary cones (equivalent to the lengths of the longest loops of Henle) did not differ between HYD and DEH quail. However, the mass of an individual medullary cone was greater in the DEH birds; this included both hypertrophy and hyperplasia of the epithelia in thick ascending limbs of Henle and hypertrophy without hyperplasia in the collecting ducts. We found no differences among groups in the sizes of tubule cross sections from cortical nephron segments (proximal tubules). Water restriction of HYD birds for 5 days as adults stimulated tubule hypertrophy but not to the same extent as the chronic regimen and with no evidence for hyperplasia. DEH quail given unrestricted water as adults maintained elevated drinking rates for the full week water was available; this rehydration had no effect on sizes of tubule epithelia. PMID- 1858936 TI - Enhancement of tumor proteolysis by TNF-alpha: correlation of in vivo isotope estimates with growth. AB - To evaluate the accuracy of in vivo estimates of protein synthesis and breakdown, measurements of plasma and tissue leucine kinetics were made in rat tumor tissues at different conditions of growth by use of constant intravenous infusion of [14C]leucine. These measurements were made in Yoshida sarcoma tumors on days 10 and 13 after implantation, with and without tumor necrosis factor (TNF) infusion and on day 10 in Walker-256 carcinosarcoma. Expressed as micromoles of leucine per gram tissue, tumor protein breakdown increased (P less than 0.01) from 0.32 +/- 0.02 to 0.52 +/- 0.09 (SE) mumol/h, with progress of the Yoshida sarcoma tumor between days 10 and 13 after implantation. Similarly, TNF increased tumor proteolysis on day 10 (0.43 +/- 0.03 mumol.h-1.g-1, P less than 0.05 vs. day 10 control) but not on day 13 after implantation of the Yoshida tumor. Estimates of growth derived from the difference between protein synthesis and breakdown rates were not statistically different from those based on actual tumor volume changes in both tumor models. However, estimates of "whole body" protein metabolism (plasma leucine flux) were not affected either by tumor aging or by treatment with TNF. This study shows that in vivo estimates of tissue protein metabolism based on our [14C]leucine constant infusion model closely reflect the growth characteristic of that tissue. A cytotoxic perfusion-independent effect for intravenous TNF on growing tumor tissue is demonstrable as increased protein breakdown. Furthermore, the commonly used concept of whole body protein metabolism, derived solely from tracer dilution in plasma, is an oversimplification. PMID- 1858938 TI - Normalized input impedance and arterial decay time over heart period are independent of animal size. AB - The arterial system of mammals in the weight range from 0.6 to 70 kg is characterized by the three-element windkessel, a succinct representation of the arterial tree consisting of the parameters peripheral resistance (Rp), total arterial compliance (C), and aortic characteristic impedance (Zc). The values of these parameters in resting conditions are related to body mass (M). The time constant, or decay time (tau), of the arterial system (defining rate of decay of aortic pressure in diastole), the product of Rp and C, is also evaluated. The dependencies of the heart period (T, inverse of heart rate), and durations of ejection (Ts) and of diastole (Td) in resting conditions are also determined as a function of M. It is found that Rp = Rp0M-0.93; Zc = Zc0M-0.97; and C = C0M+1.23, where Rp0, Zc0, and C0 are proportionality constants. Zc is thus a constant fraction of Rp in all mammals. tau is related to M as tau = tau 0M+0.29; T and Td are related to M as T = T0M+0.27 and Td = Td0M+0.30, where tau 0, T0, and Td0 are proportionality constants. The duration of diastole is thus a constant fraction of T, and the ratios T/tau and Td/tau are independent of M. The findings indicate that arterial input impedance, normalized to aortic Zc and plotted as a function of frequency normalized to heart rate, is similar for all mammals. The finding that the ratio Td/tau is the same in mammals (and Ts/T and stroke volume/M are constant) explains the constancy of pulse pressure (systolic minus diastolic pressure).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1858939 TI - Resumption of physiological functions in the wood frog (Rana sylvatica) after freezing. AB - We monitored the resumption of physiological functions in frogs that were frozen at -2 to -3 degrees C for 24 h and thawed rapidly (at 23-25 degrees C) or slowly (at 6-8 degrees C). Bodily functions were restored sooner during fast thawing, but this did not enhance the survival of frogs. The first physiological parameter to return was cardiac function, but during the early stages of thawing heart rates were lower than heart rates of unfrozen frogs at comparable body temperatures. Heart rates increased thereafter in conjunction with the rise in frog body temperatures. Spontaneous breathing and hindleg reflexes resumed after cardiac function, but neither response was exhibited by all frogs after the conclusion of the observation periods (3-4 h). Finally, isolated gastrocnemius muscles that had undergone in vitro freezing showed no significant (P greater than 0.05) impairment of twitch and tetanic tensions even as soon as 1 h after the onset of thawing. Body systems thus vary in their rates of recovery after nonlethal freezing episodes. Furthermore, recovery of specific body systems corresponds to essential needs that must be met immediately after thawing, such as reperfusion of body tissues. PMID- 1858940 TI - Excitatory pathways in smooth muscle investigated by phase-plot analysis of isometric force development. AB - Excitatory pathways in the smooth muscle of the pig urinary bladder were investigated using phase-plot analysis of isometric contractions. The phase plots, plots of the rate of change of the force as a function of the force itself, were dominated by a straight line described by the horizontal intercept (Fiso) and the vertical intercept (U). The quotient Fiso/U is a time constant that characterizes the rate-limiting step in isometric force development in the muscle. Bladder strips of 1 mm diameter were activated by electrical field stimuli, acetylcholine, potassium, and ATP in combination with selective pathway inhibitors such as verapamil, atropine, or a calcium-free solution containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. When pathways that depended significantly on depolarization or intracellular calcium release were selected, the time constant was significantly smaller, indicating a faster process. The results indicated that the rate-limiting step in force development was determined by the influx of extracellular calcium. PMID- 1858941 TI - Meal-related and rhythmic drinking: effects of abolition of rat's eating rhythm. AB - Eating and drinking in the rat, which are both highly rhythmic and nocturnal activities, are temporally and quantitatively associated. The present study abolished the rhythmicity of eating by temporally and quantitatively restricting food access to 12 equally sized bihourly meals daily (total food available was equal to 80% of daily ad libitum intake). Water access remained ad libitum and was monitored and quantified in terms of 1) nocturnality, 2) association with meals, and 3) changes in the association of food and water intake across the phases of the light-dark cycle. Similar parameters were obtained from the same rats with ad libitum access to both food and water. The results indicate that both rhythmic and meal-induced effects are detectable in the drinking of rats with restricted food access, although both the rhythmic and meal-associated factors are reduced compared with drinking under ad libitum food access. Most important, the data clearly demonstrate large changes in the association of food and water intake across the phases of the light-dark cycle. These findings indicate a complex interaction of meal-associated and rhythmic factors in the control of drinking. PMID- 1858942 TI - Hepatic portal glucagon infusion decreases spontaneous meal size in rats. AB - We describe the first tests of intraportal pancreatic glucagon infusions during spontaneous meals in undisturbed, ad libitum-fed male Sprague-Dawley rats. Two minute infusions beginning at meal onset and delivering 14 micrograms glucagon reduced the size and duration of both early and late nocturnal meals. After glucagon infusion during early nocturnal meals, neither the latency nor the size of the next meal was affected. Meal onset infusion of 3.4-14 micrograms glucagon/meal dose-dependently reduced late nocturnal meal size 19-64%. Full-meal glucagon infusions did not inhibit feeding more than 2-min infusions begun at meal onset or meal middle, despite fivefold differences in amount infused. These data indicate that spontaneous feeding is pharmacologically inhibited by prandial changes in hepatic portal glucagon concentration. PMID- 1858943 TI - Hepatic portal infusion of glucagon antibodies increases spontaneous meal size in rats. AB - Specific antibodies to pancreatic glucagon in a dose sufficient to neutralize 1.5 ng glucagon in vitro were intraportally infused during the first 2 min of spontaneous meals in ad libitum-fed male Sprague-Dawley rats. In separate tests, glucagon antibodies stimulated feeding during the first spontaneous meal of the dark phase (73% mean increase in meal size) and during spontaneous meals in the last quarter of the dark phase (58% increase). These results indicate that a glucagon-sensitive satiety mechanism has a physiological role in the control of nocturnal feeding in rats. PMID- 1858944 TI - Reduced osmotic thirst in healthy elderly men. AB - In response to water deprivation or heat stress, healthy elderly men experience reduced thirst compared with a young control group. Because water deprivation and heat stress produce hypertonicity as well as reduced extracellular fluid volume, the aim of this study was to determine whether the elderly also experience reduced thirst in response to hypertonicity without extracellular fluid volume depletion. To achieve this, after an overnight fast, healthy community-dwelling nonsmoking old (65-78 yr, n = 7) and young (20-32 yr, n = 7) men received 120-min hypertonic (0.855 M) and isotonic (0.154 M) saline infusions (0.06 ml.min-1.kg-1) in double-blind randomized order at least 2 wk apart. Both groups had increased thirst (P less than 0.001) and water intake (P less than 0.05) after the hypertonic saline infusion compared with the isotonic saline infusion. However, despite similar plasma sodium increases and less plasma volume expansion during the hypertonic saline infusion compared with the young group, the old group was less thirsty (P less than 0.01) and drank less room-temperature tap water (young 11.1 +/- 1.2 ml/kg, old 3.9 +/- 0.6 ml/kg, P less than 0.001). This reduced thirst in the old group seemed to be mainly due to a lower thirst sensitivity (P less than 0.05) to hypertonicity, although there was also a tendency toward an increased thirst threshold. Plasma arginine vasopressin increases were similar for the old and young groups with hypertonic saline, without significant changes during the isotonic saline infusion in either group. PMID- 1858945 TI - Integrating behavior and cardiovascular responses: the code. AB - The next revolution in biology is predicted to be in the integrative domain, and the need to involve physiologists in this kind of research has been recognized. This paper represents an approach to providing some of the tools required for dealing with integrative physiology at the behavioral level. Video tape recordings are made of the activities of a group of five baboons (Papio hamadryas) while simultaneous recordings of arterial blood pressure, heart rate, renal blood flow, and mesenteric or iliac blood flow are telemetered from two of the members of the group. The telemetered cardiovascular information is recorded on the two audio channels of the videotape. Subsequently the videotape is viewed, and a two-dimensional code is used to record the behavior of the two animals with the telemetry equipment. The first dimension of the code categorizes the behavior changes precisely regarding those aspects of behavior that are related to cardiovascular dynamics and does so with an accuracy of 16 ms. The second dimension codes relevant environmental changes. The paper describes the code and presents illustrations of how the code reflects the cardiovascular dynamics associated with the behavioral changes. PMID- 1858946 TI - Hemodynamic effects of endothelin-1 on ovine fetal pulmonary circulation. AB - To determine the hemodynamic effects of endothelin-1 (ET-1) in the fetal pulmonary circulation, we studied pulmonary vascular responses to brief and prolonged intrapulmonary infusions of the peptide in nine chronically prepared late-gestation fetal sheep. Left pulmonary artery (LPA) blood flow was measured with an electromagnetic flow transducer, and a catheter placed in the LPA allowed ET-1 infusion directly into the left lung. Brief (10-min) infusions of ET-1 (12.5 100 ng/min) increased flow up to 212% of baseline without changing pulmonary artery pressure. With prolonged (120-min) infusion of ET-1 (50 ng/min), flow increased from 69 +/- 8 to 164 +/- 23 ml/min at 10 min (P less than 0.05) but then declined and was not different from baseline at 120 min. The gradient between mean pulmonary artery and aortic pressures did not change, suggesting no constriction of the ductus arteriosus. Systemic (vena caval) infusion of ET-1 (100 ng/min for 30 min) caused systemic and pulmonary hypertension, as mean pulmonary artery pressure increased from 43 +/- 1 to 51 +/- 2 mmHg (P less than 0.05) and remained elevated for 30 min after cessation of the ET-1 infusion. We conclude that intrapulmonary ET-1 is a potent fetal pulmonary vasodilator, but its dilator effect is transient during prolonged infusion. In contrast, systemic infusion causes sustained hypertension, suggesting differential effects of ET-1 on the pulmonary and systemic circulations. These findings demonstrate marked vasoactivity of ET-1 in the fetus, suggesting a potential role in the normal or abnormal transitional circulation. PMID- 1858947 TI - Sleep deprivation in rats: effects on EEG power spectra, vigilance states, and cortical temperature. AB - Vigilance states, electroencephalogram (EEG) power spectra (0.25-25.0 Hz), and cortical temperature (TCRT) of 10 rats were obtained during a baseline day, a 24 h sleep deprivation (SD) period, and 2 days of recovery (recoveries 1 and 2). EEG power density in waking gradually increased in most frequencies during the SD period. Non-rapid-eye-movement (NREM) sleep was enhanced on both recovery days, and rapid-eye-movement sleep was enhanced only on recovery 1. In the initial 4 h of recovery 1, EEG slow-wave activity (SWA; mean power density 0.75-4.0 Hz) in NREM sleep was elevated relative to baseline, and the number of brief awakenings (nBA) was reduced. In the dark period of recovery 1 and the light period of recovery 2, SWA was below baseline, and nBA was increased. During the entire recovery period, SWA and nBA, both expressed as deviation from baseline values, were negatively correlated. During the SD period, TCRT was above baseline, and in the initial 16 h of recovery 1 it was below baseline. Whereas TCRT was negatively correlated with NREM sleep, no significant correlation was found between TCRT and SWA within NREM sleep. It is concluded that SD causes a short-lasting intensification of sleep, as indicated by the enhanced SWA and the reduced nBA, and a long-lasting increase in sleep duration. The different time courses of SWA and TCRT suggest that variations in NREM sleep intensity are not directly related to changes in TCRT. PMID- 1858948 TI - Characterization and development of angiotensin II receptor subtypes (AT1 and AT2) in rat brain. AB - Angiotensin II receptor subtypes (AT1 and AT2) were characterized in rat brain by displacement with the specific angiotensin antagonists Du Pont 753 and CGP 42112A, respectively, and quantitative autoradiography. Young (2-wk-old) rats expressed AT1 receptors in selected limbic system areas, structures involved in cardiovascular and fluid regulation, parts of the hippocampal formation, and the choroid plexus. In young rats, AT2 receptors were concentrated in areas involved in control and learning of motor activity, sensory areas, and selected limbic system structures. The cingulate cortex, the molecular layer of the cerebellar cortex, and the superior colliculus contained both AT1 and AT2 receptors. The number of AT1 receptors in most areas of adult (8-wk-old) rats was similar to or even higher than that present in young rats. Conversely, AT2 receptors were always much lower in number in adult animals, and in some areas they were undetectable in adults. Their differential localization and development suggest different functions for the specific angiotensin II receptor subtypes. PMID- 1858950 TI - Control of renal handling of potassium loads in ducks with active salt glands. AB - Domestic ducks adapted to saline of 400 mosmol/kgH2O as their only water supply received intravenous loads of 100 mM KCl for 2 h while being intravenously infused with 200 mM NaCl at 1.0 ml/min to produce simultaneous salt gland secretion and diuresis-natriuresis. K+ loading did not alter the plasma levels of the osmoregulatory hormones arginine vasotocin, angiotensin II, aldosterone, and atrial natriuretic factor but promptly evoked kaliuresis because of a rise from 17 to 155 mM in urinary K+, with a proportional decrease in urinary Na+. Continuous infusion of amiloride (0.04 mg.min.-1.kg body wt-1 iv) further enhanced diuresis and natriuresis and lowered urinary K+, but the kaliuretic response to K+ loading was only moderately reduced because of enhanced diuresis and a rise in urinary K+ from 3 to 33 mM, with a slight decrease in urinary Na+. Changes in plasma hormone levels reflected dehydration due to excessive diuresis but were not related to kaliuresis. Salt gland secretion was not affected directly by amiloride but was secondarily reduced by the induced dehydration. In amiloride-treated ducks, hyperkalemia in response to K+ loading was exaggerated relative to the modest reduction in K+ excretion and may be attributed to moderate metabolic acidosis and/or general effects of amiloride on K+ metabolism. It is concluded that none of the established osmoregulatory hormones is involved in short-term control of renal K+ handling in ducks and that distal tubular K+ excretion involving amiloride-sensitive Na+ channels is quantitatively unimportant in this avian species. PMID- 1858949 TI - Cholecystokinin in nucleus tractus solitarii modulates tonic and phasic gastric pressure. AB - Local excitation of neurons at the site of termination of gastric vagal afferents in the nucleus tractus solitarii (NTS) alters gastric pressure. Microinjection of one putative satiety peptide bombesin into NTS increases pressure while substance P lowers it. Therefore, we sought to determine the effects of the microinjection of cholecystokinin octapeptide (CCK-8) from micropipettes placed stereotactically into the NTS of anesthetized rats with balloons placed in the gastric antrum to sense gastric pressure waves. Sulfated CCK-8, but not nonsulfated CCK-8, produced dose-dependent decreases of gastric pressure, transient blockade of phasic waves, and subsequent dysrhythmic phasic activity. The effects were specifically related to injections into NTS and did not occur with injections given intravenously, intracisternally, or into tissue adjacent to NTS. These results support a role for CCK-8 in central regulation of not only tonic gastric pressure but also phasic activity and gastric motility. PMID- 1858951 TI - Acid-base regulation in exercising squid (Illex illecebrosus, Loligo pealei). AB - Squid (Illex illecebrosus, Loligo pealei) were cannulated in the vena cava and swum in a Beamish-type respirometer. Gas tensions and acid-base variables as well as octopine levels were estimated in samples of the mantle and of venous blood collected from quiescent, exercised, and recovered animals. When exhausted, both species exhibited a decrease in vena cava oxygen tensions and a slight alkalosis. With high swimming speeds prior to exhaustion in Illex a slight acidosis developed in the blood, which was linked to a severe intracellular acidosis. Generally, the drop in intracellular pH was linearly correlated with octopine accumulation in this species. Metabolic proton (and end-product) release from the mantle, however, was minimal, thus protecting arterial oxygen binding. High PCO2 values in the mantle of both species lead to the conclusion that the vena cava values analyzed in this and all literature studies on unrestrained cephalopods may not reflect the scope of respiratory acid-base changes in venous blood. Although metabolic changes in blood acid-base status are negligible, the respiratory acidification of venous mantle blood may allow for a classical function of Bohr and Haldane effects in these animals. PMID- 1858952 TI - Mathematical analysis of perifusion data: models predicting elution concentration. AB - System models are constructed and analyzed for combined convective flow and for dispersion in distorting concentrations of a chemical signal as it passes through a packed column. We derive general analytical solutions for these models. The results have applications to analyses such as in biological experiments involving hormonal stimulation of perifused cells, elution chromatography, adsorption columns, and studies of groundwater flow. The models reveal that the column distorts an incoming signal (such as a change in solute concentration in the flowing liquid) at the inlet. This distortion is greatest at low values of the Peclet number of the flow and is small at larger values. We explore the effects of the approximations inherent in the mathematical models of the system. Specification of the boundary conditions of the problem are shown to be particularly important. With the use of incorrect models, it is possible to obtain accurate interpolations to data obtained from perfusion experiments. However, the parameters derived (in particular the dispersion constant and the peak concentration of a solute concentration pulse) may be considerably in error. This may lead to errors when these parameter estimates are used to predict results in other experimental situations. PMID- 1858953 TI - Antagonism of endotoxic glucose dyshomeostasis by protein kinase C inhibitors. AB - Activation of protein kinase C (PKC) by bacterial lipopolysaccharide had recently been implicated in the pathogenetic sequence of gram-negative sepsis, endotoxicosis, hyperinsulinism, and the alterations in glucoregulation that eventuate in glucose dyshomeostasis. This study used the peptide antibiotic polymyxin B (PMX-B) and H-7, an isoquinoline sulfonamide, as inhibitors of PKC activation to evaluate responses to provocative insulin and glucose tolerance tests in control vs. endotoxic rats. Fed male rats were treated with either Salmonella enteritidis endotoxin (ETX; 0.33 mg/kg iv) or saline 120 min before intravenous insulin tolerance testing (IVITT) with human insulin (1 U/kg) or intravenous glucose tolerance testing (IVGTT) with D-glucose (1.2 g/kg). H-7 in dimethyl sulfoxide at 25 mg/kg, PMX-B in saline at 0.25 mg/kg, or the respective vehicles were administered 5 min before the tolerance tests. Neither H-7 nor PMX B had any significant acute effects on basal plasma glucose or lactate values. The decline in plasma with IVITT was augmented by ETX; however, concomitant H-7 or PMX-B attenuated the insulin hypoglycemia. The computed half-life of glucose in the IVGTT was decreased by ETX; however, concomitant H-7 or PMX-B decreased the tolerance alteration. In addition, both H-7 and PMX-B attenuated the rise in insulin induced by the IVGTT. Thus the hyperinsulinism and the glucoregulatory disturbances in endotoxicosis may be mediated by PKC activation and ameliorated by PKC inhibition. PMID- 1858954 TI - Effect of suckling on gastric motility in lactating rats. AB - Recent reports indicate that in male rats dehydration, LiCl, and cholecystokinin (CCK) each stimulate pituitary oxytocin (OT) secretion and also decrease gastric emptying and motility. In contrast, the present experiments demonstrate that nipple attachment and sucking by pups, a well-known stimulus for neurohypophysial secretion of OT, did not decrease gastric motility in lactating rats. Moreover, systemic injection of naloxone, which is known to potentiate the inhibitory effects of LiCl and CCK on gastric motility in male rats, had no effect on gastric motility of lactating rats while nursing. These data indicate that pituitary OT secretion from magnocellular neurons is not invariably linked to decreased gastric motility in rats. As such, our results support previous findings that inhibition of gastric motility is not secondary to the pituitary secretion of OT but allow a possible role for parvocellular oxytocinergic neurons that project from the hypothalamic paraventricular nucleus to the brain stem in the control of gastric function. PMID- 1858955 TI - High dietary sodium enhances gustatory nerve activity and behavioral responses to NaCl. AB - Neural and behavioral taste responses to NaCl were studied in rats receiving a high-salt diet. Salt preferences and voluntary sodium intake were measured by the 24-h two-bottle choice method over a wide concentration range of NaCl solutions. As expected, the salt-loaded rats showed lower preference responses for all the solutions tested, which were presented in ascending order from 0.001 to 1.0 M NaCl. However, they freely ingested significantly greater amounts of sodium than the controls by drinking larger volumes of saline solution throughout the hypotonic concentration range, from 0.001 to 0.1 M NaCl. They showed lower voluntary intake of sodium only for isotonic and hypertonic solutions. Electrophysiological recordings from the chorda tympani nerve showed that the taste responses of the salt-loaded rats were greater in magnitude than those of the controls, and the neural stimulus-response function of the experimental group had a significantly steeper slope but no apparent difference in threshold. These experiments indicate that salt-loaded rats have enhanced appetitive responses to NaCl that may be mediated by increased sensory input. PMID- 1858957 TI - Integration of vagal afferent responses to gastric loads and cholecystokinin in rats. AB - The neurophysiological responses to 2-ml intragastric saline loads and 100-pmol celiac artery infusions of cholecystokinin (CCK) were obtained from 20 vagal afferent fibers in 14 rats. Two groups of fibers were identified. Discharge rates of group I fibers (n = 16) were significantly increased by gastric loading, adapted slowly to maintained gastric volume, and were inhibited by load withdrawal. CCK elicited a significant increase in the discharge rate of these group I fibers. Prior exposure to CCK nearly doubled the response of these fibers to a subsequent gastric load. In contrast, group II fibers (n = 4) increased firing rate only during infusion of a gastric load and showed rapid adaptation and no response to CCK. CCK failed to alter subsequent responses to gastric loads in these fibers. These results 1) demonstrate an integration of signals elicited by exogenous CCK and gastric loads at the level of vagal afferent fibers and 2) imply that aspects of CCK's inhibition of food intake may derive from CCK's ability to mimic and amplify vagal afferent activity provoked by meal-related gastric events. PMID- 1858956 TI - Naltrexone, an opioid blocker, alters taste perception and nutrient intake in humans. AB - To test the hypothesis that reduced food intake produced by opioid blockade is due to a reduction in the pleasant aspects of tastes, 18 fasted male college students rated the intensity and pleasantness of soup that contained various concentrations of NaCl and of Kool-Aid that contained various concentrations of sucrose at hourly intervals after ingesting either naltrexone (50 mg) or a placebo in a double-blind study. Hunger, fullness, nausea, and current mood state were also assessed. Lunch followed and food intake was recorded. After placebo, the pleasantness of the salted soup increased as lunchtime approached. After naltrexone, however, soup pleasantness remained unchanged across time. Similar changes were obtained for perceived sweetness and pleasantness of Kool-Aid and for the perceived saltiness of soup. Naltrexone also blocked the increases in hunger ratings that occurred across time in the placebo condition. Nausea was higher after naltrexone. After naltrexone, subjects consumed approximately 500 kcal less at lunch than after placebo. Analysis of covariance suggested that decreased hunger (but not nausea or taste pleasantness) accounted for the naltrexone-induced reduction of food intake. PMID- 1858958 TI - Tetrahydrofolic acid as the principal congener of plasma folates in pigs. AB - Concentrations of pig plasma folates were determined by a high-performance liquid chromatography with an electrochemical detector (HPLC-ECD). Tetrahydrofolic acid (THF) and 5-methyltetrahydrofolic acid (5-MF) were found to be the plasma folates. The concentration of THF (10.3 +/- 4.3 ng/ml) was significantly higher than that of 5-MF (3.5 +/- 1.0 ng/ml). The sum of the THF and 5-MF concentrations determined by the HPLC-ECD analysis in Gottingen miniature pigs was comparable to the total folate concentration of the same plasma sample determined by a radioligand assay. No or only trace amounts of THF were found in the plasma of the rats, mice, rabbits, dogs, cows, horses, or humans. Although 5-MF is generally recognized as the only principal plasma folate in many species, THF may be the principal congener with 5-MF as a secondary congener in the pig. PMID- 1858959 TI - Electrophysiological evidence of baroreceptor input to area postrema. AB - Subpopulations of rat area postrema (AP) and nucleus tractus solitarius (NTS) neurons exist that are responsive to changes in blood pressure. The hypothesis that these effects may be mediated by afferent baroreceptor input was examined. Orthodromic responses of AP and NTS neurons to aortic depressor nerve (ADN) stimulation were observed. Sixty-three percent of AP neurons were affected by ADN stimulation, with most exhibiting short-duration excitatory responses (latency, 27 +/- 1 ms; duration, 11 +/- 1 ms). Fifty-five percent of NTS neurons were influenced by ADN stimulation, although effects in this region were more heterogeneous (24% of neurons excited, 31% inhibited). Thus, in the rat, apparently both AP and NTS neurons receive afferent barosensory information. PMID- 1858960 TI - Carrier-mediated mechanism for biotin transport in rabbit intestine: studies with brush-border membrane vesicles. AB - Simple diffusion has been reported as the mechanism of biotin transport in rabbit intestine. In this study, we reevaluated this concept by examining biotin transport in rabbit intestine using optimal experimental conditions and a well established brush-border membrane vesicles (BBMV) technique. Uptake of biotin by rabbit intestinal BBMV was found by an osmolarity study to be mostly the result of transport of the vitamin into an osmotically sensitive intravesicular space with little binding to membrane surfaces. Biotin transport in rabbit intestinal BBMV was 1) Na+ gradient dependent (out greater than in) with a clear "overshoot" phenomenon, indicating the accumulation of the substrate against a concentration gradient; 2) initial rate of biotin transport by the Na+ gradient-dependent component was saturable as a function of substrate concentration with apparent Km and maximum velocity (Vmax) values of 6.7 microM and 10.7 pmol.mg protein-1 x 10 s-1, respectively; 3) inhibited by high concentrations of unlabeled biotin and its related compounds desthiobiotin and thioctic acid in the presence, but not absence, of a Na+ gradient; and 4) not affected by inducing a relatively positive or negative intravesicular space with the use of valinomycin-induced K+ diffusion potential. These findings indicate that the biotin transport mechanism in rabbit intestine is carrier mediated in nature. Furthermore, this mechanism is Na+ gradient dependent, capable of accumulating the substrate against a concentration gradient and transport the vitamin via an electroneutral process. PMID- 1858961 TI - Lactate metabolism in inactive skeletal muscle during lactacidosis. AB - Contributions of carbohydrate and fat metabolism to the removal of a lactate (Lac ) load were quantified in inactive soleus (SL), plantaris (PL), and white gastrocnemius (WG) rat hindlimb muscle. Male Sprague-Dawley rats were perfused for 60 min with normal perfusate (NP, n = 8) or a high-lactate perfusate (LP, n = 8), simulating ionic conditions found in arterial blood and plasma after intense exercise: Lac- = 11.0 mM, K+ = 7.88 mM, and pH = 7.15. Metabolite fluxes across the hindlimb were calculated from blood flow and arteriovenous differences. In NP, Lac- was continuously released (2.9 +/- 0.2 mumol.min-1 x 100 g-1). However, in LP, a rapid and significant uptake of Lac- increased muscle Lac- fivefold to 39.6 +/- 1.1, 33.1 +/- 2.2, and 28.8 +/- 1.7 mumol/g dry wt in SL, PL, and WG, respectively. Glucose and O2 uptakes were similar during LP and NP perfusion. Glycerol release increased eightfold to 3.3 +/- 0.7 mumol.min-1 x 100 g-1 in response to LP. Muscle ATP, creatine phosphate, glycogen, glycolytic intermediate, and triacylglycerol concentrations did not change. However, muscle lactate-to-pyruvate ratios were elevated in all muscles of the LP group postperfusion, indicating changes in the mass action ratio at the pyruvate dehydrogenase reaction. In LP, of 80 mumol of Lac- taken up, 11% was accounted for by increased muscle Lac-, 12-24% was oxidized, and 5% may have been involved in glycerol release. The remaining Lac- may have been involved in metabolic cycling along the glyconeogenic-glycolytic pathway and/or in triacylglycerol-free fatty acid substrate cycling. PMID- 1858962 TI - Immune response to Plasmodium berghei sporozoite antigens. I. Evaluation of murine T cell repertoire following immunization with irradiated sporozoites. PMID- 1858963 TI - Comparative susceptibility of anopheline mosquitoes to Plasmodium falciparum in Rondonia, Brazil. AB - Five anopheline species, Anopheles deaneorum, An. albitarsis, An. triannulatus, An. oswaldoi, and An. mediopunctatus were compared to An. darlingi for susceptibility to infection by P. falciparum in Costa Marques, Rondonia, Brazil. Laboratory reared F1 An. darlingi and anopheline test species were allowed to feed at the same time on falciparum malaria patients who had gametocytes in their blood, and who had not yet been treated with quinine. Mosquitoes were dissected and examined for oocysts on day 9, and for sporozoites on days 16-20 after feeding. Anopheles mediopunctatus had higher mean numbers of oocysts and oocyst positive rates than An. darlingi. The oocyst positive rate and the mean number of oocysts in An. deaneorum and An. darlingi were similar. Anopheles triannulatus and An. oswaldoi had fewer oocysts than An. darlingi. The salivary gland sporozoite infection rate was similar for An. mediopunctatus and An. deaneorum and much lower for An. triannulatus and An. oswaldoi when compared to An. darlingi. Anopheles albitarsis developed oocysts, but sporozoites did not invade the salivary glands. In relative levels of susceptibility to P. falciparum, An. darlingi was equal to An. mediopunctatus which was greater than An. deaneorum, which was greater than An. triannulatus, which was greater than An. oswaldoi. PMID- 1858964 TI - Infection of Anopheles darlingi fed on patients with Plasmodium falciparum before and after treatment with quinine or quinine plus tetracycline. AB - Anopheles darlingi fed on eight falciparum malaria patients with gametocytes before and after treatment with quinine sulfate or quinine sulfate plus tetracycline became infected. Quinine and quinine plus tetracycline had no apparent sporontocidal or gametocytocidal effect on late stage immature and mature gametocytes. Plasmodium falciparum gametocytes are persistent and infected mosquitoes for up to 21 days after patients were treated with quinine plus tetracycline. Sporogonic development was similar for groups of mosquitoes fed before and after patients were treated with these schizontocides. The percentages of infected mosquitoes that developed salivary gland infections were also similar for groups of mosquitoes fed before and after treatment. Twenty-four hours after treatment with 45 mg of primaquine phosphate, falciparum malaria patients were not infective to An. darlingi. PMID- 1858965 TI - A comparison of non-radioactive labeling and detection systems with synthetic oligonucleotide probes for the species identification of mosquitoes in the Anopheles gambiae complex. AB - Different non-radioactive probe labeling and detection systems were used with pAnaI, a species-specific oligonucleotide probe that distinguishes male Anopheles gambiae and An. arabiensis mosquitoes. Comparisons have been made between the performance of each technique with respect to sensitivity and specificity against DNA dot-blots and mosquito squashes. Their relative costs, economy, and ease of use were analyzed in an attempt to develop an appropriate non-radioactive system for use in the field. Enzyme-labeled probes that were detected directly by label activity proved more suitable than probes requiring reporter molecules for detection. Binding of reporter molecules to mosquito squashes caused the appearance of false positives and, in addition, their binding to nylon filters caused high background coloration. Chemiluminescent detection provided an attractive alternative to colorimetric detection. Both systems analyzed were rapid, simple, and economic. However, less severe treatment of filters was required for reprobing with chemiluminescence. The greatest sensitivity achieved was with chemiluminescent detection in which the limit of detection was 0.15 ng of target DNA. This study suggests that a synthetic DNA probe coupled to a chemiluminescent detection system should provide a sufficiently simple, sensitive, and reliable technique for insect vector identification in the field. PMID- 1858966 TI - Cellular proliferative responses in squirrel monkeys immunized with recombinant and synthetic Plasmodium vivax circumsporozoite peptides. AB - The role of circulating peripheral blood momonuclear cells (PBMC) in mediating protective immunity was examined during an immunization trial in Saimiri monkeys. Three engineered constructs representing different but overlapping regions of the circumsporozoite (CS) protein of Plasmodium vivax were used to immunize the Saimiri monkeys. Monkeys were randomly placed into three immunization groups: rPvCS2, rPvCS3, and LCV3 (representing three different but overlapping portions of the P. vivax CS protein) and two control groups: an alum adjuvant control group and an unimmunized control group. Collections of PBMC were made throughout the study at weeks 0, 2, 8, challenge (week 16), and two weeks after challenge. Proliferative responses to all immunogens and pokeweed mitogen were measured in all monkeys. Fourteen of 18 monkeys immunized with either rPvCS2 or rPvCS3 responded on the day of challenge to the appropriate immunogen with a stimulation index less than 2. Immunization with LCV3, which represents the repeat region only, elicited a specific response in only one monkey. However monkeys in both control groups also responded to rPvCS2 and rPvCS3, regardless of immunization, suggesting the presence of epitopes in rPvCS2 and rPvCS3 capable of associating with differing MHC antigens. Furthermore, the frequency of these cells in the periphery was increased by immunization, as demonstrated by a greater number of responding monkeys in the rPvCS2 and rPvCS3 immunized groups. PMID- 1858967 TI - Resistance to antimalarials by Plasmodium falciparum in Arso PIR, Irian Jaya, Indonesia. AB - Between 1987 and 1990, susceptibility of Plasmodium falciparum to chloroquine and to Fansidar was measured in vivo in 151 volunteers using the standard 7-day test. All volunteers lived in Arso PIR, Irian Jaya. A 25 mg/kg dose of chloroquine base was administered over a three-day period to 92 volunteers positive for P. falciparum rings (greater than 10 rings/200 white blood cells). Fifty volunteers (54%) showed results consistent with resistance. Twenty-nine were classified RII, and 21 RIII. In November 1989, a single curative dose of Fansidar was administered to 59 volunteers divided among three groups with 18 months, four years, and life-long exposure to endemic malaria. The proportion of volunteers in each group still positive for P. falciparum on day 7 of followup was 54%, 0%, and 14%, respectively. Thus, immune status profoundly effected clinically response to Fansidar. Standard in vitro microtests were also performed on parasites from 11 volunteers against chloroquine, amodiaquine, quinine, pyrimethamine/sulfadoxine, and and mefloquine. Nine of ten isolates showed in vitro growth consistent with resistance to chloroquine. Tests with other drugs showed few isolates with results considered indicative of susceptibility. Arso PIR has a severe drug resistance problem. PMID- 1858968 TI - Characterization and classification of leishmanial parasites from humans, wild mammals, and sand flies in the Amazon region of Brazil. AB - Ninety-four leishmanial isolates from the Brazilian Amazon Region (Amapa, Amazonas, Para, and Rondonia) were identified and classified using specific monoclonal antibodies and an indirect radioimmunoassay (serodeme analysis); eighty-two were also characterized by enzyme electrophoresis (zymodeme analysis), the results of which were subjected to a numerical phenetic analysis. Six isolates from humans (3), Didelphis marsupialis (1), Lutzomyia olmeca nociva (1), and Lu, reducta (1) showed reactivity patterns and isoenzyme profiles similar to those obtained with the Leishmania amazonensis reference strains, and were identified as this species. Eighty-six stocks were classified as members of the L. braziliensis complex; of these, 61 were L. guyanensis or variants, which presented three serodeme subtypes, but whose isoenzyme profiles were all similar to the reference strain. A total of 15 isolates were distinguished as L. braziliensis or variants and were classified into five serodeme subtypes. The isolate from Psychodopugus davisi appeared, from the numerical analysis, to be a distinct parasite species. Ten isolates showed reactivity patterns and isoenzyme profiles similar to those obtained with the L. naiffi reference strain. A parasite isolated from Ps. claustrei appeared to be different from all reference strains by both techniques, and was classified as probably being a new species. The importance of these results with respect to the taxonomic status of the New World Leishmania, and their implications for both clinical and epidemiologic data are discussed. PMID- 1858969 TI - Five cases of encephalitis during treatment of loiasis with diethylcarbamazine. AB - Five cases of encephalitis following treatment with diethylcarbamazine (DEC) were observed in Congolese patients with Loa loa filariasis. Two cases had a fatal outcome and one resulted in severe sequelae. The notable fact was that this complication occurred in three patients hospitalized before treatment began, with whom particularly strict therapeutic precautions were taken, i.e., initial dose less than 10 mg of DEC, very gradual dose increases, and associated anti-allergic treatment. This type of drug-induced complication may not be that uncommon in highly endemic regions. It occurs primarily, but not exclusively, in subjects presenting with a high microfilarial load. The relationship between the occurrence of encephalitis and the decrease in microfilaremia is evident. The pathophysiological mechanisms are discussed in the light of these observations and the few other comments on this subject published in the literature. PMID- 1858970 TI - Evaluation of a monoclonal-antibody based antigen assay for diagnosis of Wuchereria bancrofti infection in Egypt. AB - Conventional methods for diagnosis of Wuchereria bancrofti infection are insensitive and often impractical because of the need for night blood collections. A sensitive and specific antigen detection assay has been developed for W. bancrofti, which is based on a monoclonal antibody (AD12) that binds to a repeated epitope on a 200 kDa adult worm excretion product present in sera from infected humans. The only formal evaluation of this assay to date was performed with sera from India. In the present study, we have evaluated the performance of the AD12 antigen assay in two laboratories with sera collected in endemic and non endemic areas in Egypt. Antigen was detected in 57 of 59 (97%) sera from microfilaremic subjects, and in 22 of 139 asymptomatic and amicrofilaremic subjects who reside in a highly endemic area. Antigen titers were significantly correlated with microfilaria counts (r = 0.41, P less than 0.01). Filarial antigen was not detected in most sera from amicrofilaremic subjects with clinical filariasis. Comparative antigen test results obtained from laboratories in Cairo and St. Louis agreed in 170 of 173 sera tested. Filarial antigen was not detected in sera from Egyptians with no history of residence in filaria-endemic areas. Specifically, nonendemic sera from patients with other parasitic infections (schistosomiasis, fascioliasis, ascariasis, etc.) were uniformly negative in the assay. We conclude that the AD12 filarial antigen assay is sensitive and specific for W. bancrofti infection in Egypt. PMID- 1858971 TI - The response to chemotherapy of serum Mycobacterium leprae-specific antigen in multibacillary leprosy patients. AB - We have examined the Mycobacterium leprae phenolic glycolipid-I (PG-I) antigen levels in the sera of 45 multibacillary leprosy patients commencing chemotherapy. The PG-I antigen levels correlated with the bacterial and morphological indices, but not with the serum IgM anti-PG-I antibody levels. Antigen levels were significantly higher in patients with diffuse skin infiltration, but did not vary significantly with other parameters reflecting the duration and extent of untreated disease. The PG-I antigen levels in 27 patients examined serially decreased consistently over the first year of multidrug therapy. PMID- 1858972 TI - Sister chromatid exchange in lymphocytes of patients with cancer of the larynx. AB - The frequency of sister chromatid exchange (SCE) was studied in cultured peripheral lymphocytes from 15 untreated patients with carcinoma of the larynx and 10 healthy control subjects. Bromodeoxyuridine-incorporated chromosomes were treated with Hoechst 33258 and stained according to conventional methods. To measure SCE frequency, at least 15 mitoses per donor were evaluated. The SCE values were found to be higher in cancer cases than in control cases. PMID- 1858973 TI - Recurrent respiratory papillomatosis: progression to invasion and malignancy. AB - Recurrent respiratory papillomatosis is the most common benign tumor of the larynx in children. The disease often runs a protracted course necessitating multiple endolaryngeal procedures. Rarely, these papillomata become invasive and/or undergo malignant degeneration. A case report of malignant degeneration and widespread invasion in long-standing laryngeal papillomatosis and a review of the relevant literature are presented. PMID- 1858974 TI - Bronchogenic cysts: a cause of stridor in the neonate. AB - Bronchogenic cyst of the mediastinum, a cause of stridor in the neonate, is one of a group of congenital lesions of the mediastinum that results from abnormal budding of the ventral segment of the primitive foregut. A review of our treatment of 15 patients over 10 years at Le Bonheur Children's Medical Center is highlighted by a case report of a newborn with stridor and severe respiratory distress caused by a mediastinal bronchogenic cyst. We assess the literature on these rare but life-threatening lesions, and discuss the embryology, diagnostic work-up, and treatment, emphasizing the roles of different radiologic modalities in evaluating patients. PMID- 1858975 TI - Clinical radiology quiz. PMID- 1858976 TI - Temporal bone histopathology: residents' quiz. Endolymphatic hydrops (Meniere's disease). PMID- 1858977 TI - Free flap reconstruction of recalcitrant hypopharyngeal stricture. AB - A case report is presented of the use of a jejunal microvascular free flap for the reconstruction of a hypopharyngeal stricture caused by caustic ingestion. Although the airway was reestablished, there was aspiration and diplophonia. This case is discussed as an example of an effective treatment of a difficult problem, but one posing secondary problems arising from the use of jejunum. PMID- 1858978 TI - Early structural changes in vascularized periosteal flaps studied in situ. AB - This study examines the very early stages of osteogenesis in vascularized periosteal flaps and completes a characterization of their behavior after decortication. Pleuroperiosteal flaps based on the intercostal artery were developed in nine dogs and studied in situ by histologic and tetracycline fluorescence methods over periods varying from 1 to 7 days. The earliest changes were noted at 72 hours and were characterized by cellular and capillary proliferation, osteoid deposition, and bright fluorescence. The potential function of retained osseous spiculae was investigated separately. It was concluded that microscopic fragments of mature bone trapped within the flaps appear to assist and consolidate new bone formation. PMID- 1858979 TI - Chronic toxic encephalopathy investigated using dynamic posturography. AB - Seven male patients previously exposed to industrial solvents and diagnosed with chronic toxic encephalopathy (aged 38 to 69 years; mean age, 56 years) were investigated by dynamic posturography and compared with healthy, age-matched male control patients. Dynamic posturography comprises two phases: a sensory organization (SO) phase, in which the support surface and visual surround are either stable or referenced to the patient's sway, with eyes open or closed, and a movement coordination (MC) phase, in which the platform makes active movements. In SO testing, the patient group showed significantly impaired equilibrium performance compared with the control group in most test conditions. The MC test revealed no differences between groups. A relationship was found between the equilibrium score resulting from SO testing with stable support and visual surround and the sway area of the confidence ellipse elicited 3 years previously by static posturography with eyes open. We conclude that patients with chronic toxic encephalopathy have impaired equilibrium, as demonstrated by dynamic posturography testing. PMID- 1858980 TI - Quantitation of DNA and protein impurities in biopharmaceuticals. AB - The development of drugs and biologicals for human injection generated from recombinant DNA and hybridoma technologies has resulted in new standards for product purity. We discuss the regulatory position relative to impurities in these biopharmaceuticals, focusing on the analytical goals for quantitation. Current methods for making these measurements are reviewed, and a new system designed for improved analysis is described. Assay results for both contaminating DNA and proteins are presented. PMID- 1858981 TI - Determination of boron in tissues and cells using direct-current plasma atomic emission spectroscopy. AB - We have developed a safe, simple, and efficient method for boron determination by means of direct-current plasma atomic emission spectroscopy. Tissues were solubilized by using concentrated sulfuric acid and 70% hydrogen peroxide to digest the samples without the need of high temperatures and pressures. Boron cluster compounds could be measured with sensitivity, precision, and accuracy similar to those of boric acid standards. Results obtained with [(C2H5)3NH]2B12H12, Cs2B12H11SH.H2O, and C15H32B10O6 show that this analytical method is applicable to a variety of compounds with different chemical structures. A sensitivity of 0.1 ppm has been obtained with known standards alone and in a variety of tissue matrices including tumor, blood, liver, skin, and cell suspensions. The measurement of total boron by direct-current plasma atomic emission spectroscopy (DCP-AES) has been achieved with as little as 50 mg of tissue or as few as 5 x 10(7) cells. The procedure is applicable to the analysis of boron in the ppm range with a high degree of precision and accuracy. PMID- 1858982 TI - Stable isotope ratio analysis at trace concentrations using degenerate four-wave mixing with a circularly polarized pulsed probe beam. AB - Stable isotope analysis based on vectorial optical-phase conjugation by resonant degenerate four-wave mixing (D4WM) is reported by using a D4WM method with vertically polarized pump beams and a circularly polarized probe beam. Since the polarization of the signal beam is different from that of the pump beams, the background radiation is suppressed more effectively. Excellent sensitivity, high spectral resolution, and efficient optical detection make this an effective and unusually convenient nonlinear spectrometric method for the analysis of trace amounts of stable isotopes. Using an excimer-pumped pulsed dye laser, the fine structures of lithium are examined. A detection limit of 2.5 ng/mL lithium is observed while a Doppler-free resolution is maintained by using transient "coherent-grating" based D4WM spectroscopy. PMID- 1858983 TI - Determination of radium isotope ratios and abundances in geologic samples by thermal ionization mass spectrometry. AB - We describe chemical separation and mass spectrometric procedures for the measurement of radium isotopes in geologic samples. These methods provide 226Ra/228Ra ratio measurements for 1 g or less of rock sample containing subpicogram amounts of radium with precision better than 1.5% (95% confidence level). Radium-226 concentrations were measured by isotope dilution for smaller sample sizes (100-500 mg) containing as little as 1-10 fg of total 226Ra with similar high precision. PMID- 1858984 TI - Isotopic determination of organic keto acid pentafluorobenzyl esters in biological fluids by negative chemical ionization gas chromatography/mass spectrometry. AB - A rapid, single-step procedure for the extraction and derivatization of organic alpha-keto acids from microliter quantities of human plasma has been developed. The keto acids were analyzed as the pentafluorobenzyl (PFB) ester by methane negative chemical ionization gas chromatography/mass spectrometry. The PFB esters possess excellent chromatographic properties and required no further derivatization to block the keto group. They fragment to produce intense carboxylate anions, often as the sole ion in the spectrum, and offer detection limits below 1 pmol. This derivative is suitable for isotopic analysis of organic keto acids because it does not introduce any additional isotopic complexity into the target molecule. Normal human plasma 4-methyl-2-oxopentanoic acid levels were 34.9 +/- 5.3 mumol.L-1 and could be determined with 1.1% precision by isotope dilution GC/MS. We have used this procedure to study leucine and 4-methyl-2 oxopentanoic acid metabolism by using stable isotopically labeled tracers in a variety of normal and abnormal conditions. PMID- 1858986 TI - Isoflurane impairs the function of ischemic myocardium in acutely but not in chronically instrumented dogs. AB - To compare the effects of isoflurane on ischemic myocardium in acutely and chronically instrumented animals, 12 mongrel dogs were monitored with electromagnetic or Doppler ultrasonic flow transducers and hydraulic occluders around the left circumflex coronary artery, pressure transducers in the left ventricle, and heparin-filled catheters in the descending aorta. Regional function of normal and ischemic myocardium was assessed by sonomicrometry. The hemodynamic effects of isoflurane (2% inspired concentration) were more pronounced in the acutely than in the chronically instrumented dogs. Decreases in mean arterial pressure (-47% +/- 5% in the acute and -22% +/- 4% in the chronic preparation, P less than 0.01), left ventricular contractility (-51% +/- 6% and 33% +/- 4%, P less than 0.01), and coronary perfusion pressure (-59% +/- 6% and 12% +/- 9%, P less than 0.01) were more distinct in the acutely instrumented animals. Although the reduction of regional function during isoflurane anesthesia was similar in normal myocardium in both preparations (-33% +/- 4% acute and -34% +/- 6% chronic preparation, not a significant difference), an exaggerated dysfunction was observed in the ischemic myocardium of the acutely instrumented dogs (-66% +/- 2% and -30% +/- 4%, P less than 0.01). It is concluded that acutely instrumented dogs respond to the hemodynamic effects of isoflurane, resulting in ischemic myocardial dysfunction, significantly more than do chronically instrumented dogs. PMID- 1858985 TI - Hemodynamic responses to endotracheal extubation after coronary artery bypass grafting. AB - After coronary artery bypass grafting (CABG) surgery, patients may remain at risk for myocardial ischemia and infarction and ventricular dysrhythmias. The hemodynamic responses to endotracheal extubation and the efficacy of intravenous lidocaine pretreatment were studied after CABG surgery and overnight mechanical ventilation. Twenty-five patients were divided into two groups: group 1 (n = 13) patients who had tracheal extubation after pretreatment with a placebo; group 2 patients who received lidocaine (1 mg/kg IV) before tracheal extubation. Hemodynamic data, electrocardiographic tracings, and arterial blood gases were obtained before tracheal extubation, during suctioning, and 1, 5, and 20 min after tracheal extubation. Group 1 patients displayed significant increases in heart rate, arterial blood pressure, rate-pressure product, right atrial pressure, and cardiac index during suctioning and within 1 min of tracheal extubation, returning to preextubation level by 5 min. There were no significant changes in pulmonary and systemic resistance indices. Hemodynamic changes in group 2 patients were similar to those in group 1. Both in the absence and presence of lidocaine, tracheal extubation caused hemodynamic responses that were small in magnitude and brief in duration. These responses were not associated with electrocardiographic or enzymatic evidence of myocardial ischemia or infarction, or with ventricular dysrhythmias. Compared with the well-documented hemodynamic responses to tracheal intubation, we found that extubation of the trachea after CABG surgery was associated with less pronounced responses. This may be related to avoidance of laryngoscopy and possibly accommodation to the endo-tracheal tube. These modest hemodynamic responses of extubation of the trachea after CABG surgery were not modified by intravenous lidocaine. PMID- 1858987 TI - Effects of atracurium and pancuronium on the oculocardiac reflex in children. AB - The authors compare the effect of two muscle relaxants, atracurium and pancuronium, on the bradycardia resulting from the oculocardiac reflex during eye surgery for strabismus in children. Two groups, each composed of 15 children, received either pancuronium or atracurium during strabismus operations. Heart rate and rhythm were observed at several points during the operations, and the changes that occurred in the two groups were compared. We found that the incidence and severity of the bradycardia, the incidence of dysrhythmias, and the need for atropine administration were significantly greater in the atracurium group than in the pancuronium group. PMID- 1858988 TI - Scalp infiltration with bupivacaine in pediatric brain surgery. AB - To evaluate whether local anesthetic scalp infiltration blunts hemodynamic responses to craniotomy in anesthetized children (age, 2-18 yr), two concentrations of bupivacaine (0.125% and 0.25%) with vasoconstrictor (epinephrine 1:400,000) were compared with control data when a solution of vasoconstrictor alone was injected. Arterial plasma levels of bupivacaine were measured by high-pressure liquid chromatography. Statistically significant increases in mean arterial pressure and heart rate above baseline measurements occurred in the control group during the period between scalp incision and dural reflection (P less than 0.05). Both concentrations of bupivacaine prevented these increases. Mean arterial pressure and heart rate during scalp incision and scalp reflection were significantly higher in the control group than in both bupivacaine groups (P less than 0.05). Peak bupivacaine plasma levels (mean +/- SD) occurred either 5 or 10 min after infiltration and were significantly higher in the 0.25% group (0.48 +/- 0.31 microgram/mL) than the 0.125% group (0.14 +/- 0.13 microgram/mL) (P less than 0.05). These results suggest that bupivacaine infiltration blocks the hemodynamic response to craniotomy. A concentration of 0.125% bupivacaine with 1:400,000 epinephrine is as effective as 0.25% bupivacaine with 1:400,000 epinephrine at reducing the hemodynamic response to craniotomy. Because the lower concentration of bupivacaine produces lower blood levels, we recommend 0.125% bupivacaine with 1:400,000 epinephrine as a useful, safe adjunct to general anesthesia in children undergoing craniotomy. PMID- 1858989 TI - Left ventricular performance during propofol or methohexital anesthesia: isotopic and invasive cardiac monitoring. AB - Using gated radionuclide ventriculography and invasive cardiac monitoring, the effects of propofol and methohexital on left ventricular volumes and function were investigated in 22 unpremedicated patients (ASA physical status III, 50-78 yr) with chronic coronary artery disease (NYHA class II-III). Anesthesia was induced with either propofol or methohexital (2 mg/kg), followed by a maintenance infusion of 100 micrograms.kg-1.min-1. Vecuronium (0.05 mg/kg) was administered and ventilation (FIO2, 1.0) was manually controlled (FECO2, 0.04-0.05). Data acquisitions were serially obtained over 15 min. Propofol and methohexital anesthesia caused an average 15% decrease in mean arterial pressure, associated with a 20% decrease in cardiac index without a decrease in systemic vascular resistance index. It is interesting that the determinants of these hemodynamic effects were different. Heart rate did not change during propofol infusion despite the decrease in mean arterial pressure, whereas heart rate increased during methohexital infusion. In the propofol group, the decrease in cardiac index was associated with decreases in indicators of preload (end-diastolic volume and pulmonary capillary wedge pressure), whereas end-systolic volume and global ejection fraction did not change statistically. In the methohexital group, the decrease in cardiac index was associated with a decrease in global ejection fraction and an increase in end-systolic volume, whereas indicators of preload remained unchanged. It is concluded that methohexital reduces left ventricular performance. In contrast, propofol preserves left ventricular performance despite a likely negative inotropic effect. PMID- 1858990 TI - Clinical and metabolic responses to different types of premedication. AB - Clinical and metabolic responses to three types of premedication were studied in ASA physical status I patients given any one of the following: (a) 0.5 mg of atropine and 50 mg of meperidine given intramuscularly plus an oral placebo tablet (n = 14), (b) 10 mg of oral diazepam and an intramuscular placebo (2 mL NaCl, concentration = 0.9) (n = 14), or (c) oral and intramuscular placebo (n = 14). Based both on subjective estimates (tiredness, fear, anxiety, dryness of mouth) and, especially, on metabolic responses (energy expenditure, oxygen consumption), oral diazepam appears to be superior to the combination of an opiate (meperidine) plus an anticholinergic (atropine). Atropine plus meperidine significantly increased energy expenditure above predicted values (2061 +/- 365 vs 1714 +/- 361 kcal/24 h, P = 0.004), calculated using the Harris-Benedict equation, based on sex, weight, height, and age, as well as increased oxygen consumption above levels seen with diazepam premedication (160 +/- 29 vs 137 +/- 17 mL.min-1. m-2). These findings indicate an iatrogenic stress factor induced by premedication with atropine plus meperidine. PMID- 1858991 TI - Blood pressure measurement by arterial tonometry in controlled hypotension. AB - A newly developed arterial tonometer enabled us to measure the blood pressure waveforms in addition to determining systolic and diastolic pressures noninvasively and continuously. Twenty-eight adult patients undergoing orthopedic surgery under controlled hypotension were studied. Systolic blood pressure was reduced to two-thirds of baseline values with an infusion of nitroglycerin during nitrous oxide/enflurane anesthesia. Intraarterial blood pressures were simultaneously measured in either the right or the left radial artery with a cannula and a Gould P23XL calibrated transducer; tonometric monitoring was performed on the contralateral radial artery using a Colin CBM-3000 instrument. The outputs of the two blood pressure measurement instruments were recorded for later data analysis. The shape of the tonometric pressure waveform was nearly identical to the waveform recorded intraarterially even during controlled hypotension. Regression analyses of 2039 paired tonometric and intraarterial blood pressure values during the hypotensive period showed good correlations (r = 0.78 for systolic, r = 0.81 for mean, and r = 0.70 for diastolic pressures). The accuracy of systolic, mean, and diastolic readings was from 4 to 7 mm Hg with negligible bias and did not differ significantly among six systolic, four mean, and four diastolic pressure groups. Our results indicate that arterial tonometry can provide accurate, reliable, and real-time monitoring of blood pressure even during controlled hypotension. PMID- 1858992 TI - Mixtures of sodium nitroprusside and trimethaphan for induction of hypotension. AB - A mixture of sodium nitroprusside (SNP) and trimethaphan, empirical 1:10 weight ratio, has been advocated to decrease untoward side effects of SNP when used to induce hypotension during anesthesia and operation. The purpose of this study was to investigate the effects of various ratios of mixtures of SNP and trimethaphan on heart rate (HR), renal sympathetic nerve activity (RSNA), and renal artery blood flow to find the best ratio of SNP and trimethaphan for producing induced hypotension. Five mixtures with different ratios of SNP and trimethaphan, as well as each drug alone, were given intravenously to mongrel dogs in amounts adequate to achieve a stable mean arterial blood pressure of 75 +/- 5 mm Hg. Sodium nitroprusside alone significantly increased HR (163% +/- 14.5%) and RSNA (222% +/ 24%). Trimethaphan alone significantly decreased RSNA (11.6% +/- 4.5%). There were significant positive correlations between SNP-to-trimethaphan ratios and percent changes in HR (r2 = 0.301, P less than 0.01) and in RSNA (r2 = 0.648, P less than 0.01). Renal artery blood flow was well maintained with all ratios. Sodium nitroprusside and trimethaphan interacted synergistically to produce hypotension. However, they antagonize each other in their effects on arterial baroreflex-mediated changes in HR and RSNA. According to linear regression lines, HR changed least with a SNP-to-trimethaphan ratio of 1:5, and RSNA changed least with SNP-to-trimethaphan ratios of 1:2.5 and 1:5. Our results indicate that mixtures of SNP and trimethaphan in ratios of approximately 1:2.5 to 1:5 may produce induced hypotension with stable reflex sympathetic nerve activity. PMID- 1858994 TI - Recovery of pancuronium from peritoneal dialysate in a severely burned child. PMID- 1858993 TI - Effects of isoflurane, midazolam, and etomidate on cardiovascular responses to stimulation of central nervous system pressor sites in chronically instrumented cats. AB - The systemic hemodynamic actions of isoflurane (a volatile anesthetic) and etomidate and midazolam (intravenous anesthetics) have been well documented. However, few studies have investigated the actions of these agents on central cardiovascular control sites. The present investigation examined the actions of these agents on the responses of systolic arterial pressure (SAP), heart rate, infrarenal aortic blood flow, and lower body vascular resistance to central nervous system pressor site stimulation in chronically instrumented cats. Male and female cats (n = 23) were chronically instrumented with bipolar stimulating electrodes in the regions of the ventrolateral hypothalamus (anterior, 10.0 mm; lateral, 2.5 mm; depth, -4.0 mm) and mesencephalic reticular formation (anterior, 2.0 mm; lateral, 2.0 mm; depth, -1.0 mm). Control experiments consisted of stimulation sequences at 1x, 2x, and 4x threshold current levels to elicit pressor responses. Stimulation of the hypothalamic site produced current dependent increases in SAP (6-85 mm Hg), in heart rate (3-56 beats/min), and in infrarenal aortic blood flow (0-85 mL/min). Reticular formation site stimulation produced graded increases in SAP (6-129 mm Hg) only. Isoflurane (1.5%, 2.5%, and 3.0%), etomidate (3.0-mg/kg bolus and 0.4-mg.kg-1. h-1 infusion), and midazolam (7.5-mg/kg bolus and 0.2-mg.kg-1.h-1 infusion) were then administered in separate experimental groups. After a steady hemodynamic state was established with each agent, stimulation sequences were repeated. Isoflurane produced an attenuation of the responses of SAP (from 85.1 +/- 8.2 to 17.8 +/- 6.1 mm Hg at 1.5%, to 7.2 +/- 2.0 mm Hg at 2.5%, and to 4.7 +/- 2.0 mm Hg at 3%, all P less than 0.05), heart rate (from 41.1 +/- 13.0 to 12.5 +/- 2.7 beats/min at 2.5% and to 6.2 +/- 1.7 beats/min at 3%, all P less than 0.05), and of the infrarenal aortic blood flow (from 72.6 +/- 14.3 to 11.8 +/- 4.2 mL/min at 1.5%, to 10.2 +/- 5.6 mL/min at 2.5%, and to 3.2 +/- 1.5 mL/min at 3%, all P less than 0.05) to the highest level of hypothalamic site stimulation. Isoflurane similarly produced an attenuation of the SAP response (from 128.7 +/- 10.3 to 15.4 +/- 8.1 mm Hg at 1.5%, to 0.2 +/- 1.1 mm Hg at 2.5%, and to 0.3 +/- 0.5 mm Hg at 3.0%, all P less than 0.05) to the highest level of reticular formation site stimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1858995 TI - Bronchospasm after intramuscular 15-methyl prostaglandin F2 alpha and endotracheal intubation in a nonasthmatic patient. PMID- 1858996 TI - Anterior spinal artery syndrome after epidural anesthesia in a pregnant diabetic patient with scleredema. PMID- 1858997 TI - Epidural air associated with multiradicular syndrome. PMID- 1858998 TI - Complete airway obstruction of armored endotracheal tubes. PMID- 1858999 TI - Erroneous measurement with invasive monitoring of blood pressure. PMID- 1859000 TI - A potential hazard associated with misunderstanding of pulse oximetric readings. PMID- 1859001 TI - Transient anisocoria after intravenous administration of butylscopolamine. PMID- 1859002 TI - Another cause for obstruction of intravenous infusion tubing. PMID- 1859003 TI - Of stethoscopes and stopcocks. PMID- 1859004 TI - Alfentanil infusion for postoperative pain: a comparison of epidural and intravenous routes. AB - The efficacy of intravenous (iv) and epidural infusions of alfentanil for postoperative pain relief was investigated in 24 patients (ASA physical status 1 2) who were scheduled for abdominal hysterectomy. The patients were allocated randomly to receive either epidural or iv alfentanil. In both groups, a loading dose of 15 micrograms.kg-1 was administered, followed by a constant rate infusion of 18 micrograms.kg-1.h-1 alfentanil for 20 h. Both routes provided similar degrees of analgesia; however, analgesia occurred earlier in the intravenously treated group (P less than 0.03). Mean plasma alfentanil concentrations (Cps) varied between 42 and 82 ng.ml-1 in the iv group and 23 and 68 ng.ml-1 in the epidural group, with higher concentrations in the iv group for the first 60 min only (P less than 0.01). Cps increased with infusion time, suggesting accumulation of alfentanil. After infusion ended, pain recurred at the same time in both groups, whereas the alfentanil Cps still were greater than 45 ng/ml. Postoperative epinephrine concentrations decreased after 60 min of infusion (P less than 0.02), whereas, after 6 h, cortisol levels decreased to preoperative values. Norepinephrine concentrations decreased only slightly. The only clinically meaningful effect on vital signs that occurred was an abrupt reduction of respiratory rate after the iv loading dose. PaCO2 increased to the same extent in both groups during the first 15 min only. The incidence of opioid-related side effects was similar in both groups. These results suggest that the iv and epidural routes were equally effective for providing postoperative pain control and controlling the postoperative response to surgical stress. PMID- 1859005 TI - Flumazenil antagonism of midazolam-induced ventilatory depression. AB - Flumazenil, a benzodiazepine antagonist, reliably reverses midazolam-induced sedation; however, its effect on respiratory depression has not been established completely. Twelve healthy volunteers received sufficient midazolam (0.13 +/- 0.01 mg.kg-1 mean +/- SE) to render them unresponsive to verbal command; they then received flumazenil 1.0 mg or placebo (flumazenil vehicle) in a randomized, double-blind fashion. Ventilatory drive was measured before and after administration of midazolam, as well as 3, 30, 60, and 120 min after administration of flumazenil or placebo. Seven to 30 days later, the study was repeated, with subjects receiving placebo or flumazenil (whichever they had not received during their first trial). Midazolam caused significant decreases in the slope of the CO2 response (-29 +/- 5%; P less than 0.005); minute ventilation (VE) at end-tidal CO2 tension (PETCO2) = 46 mmHg (-28 +/- 4%; P less than 0.001), and tidal volume at PETCO2 = 46 mmHg (-44 +/- 4%; P less than 0.005). Three minutes after intravenous administration of flumazenil 1.0 mg, VE46 and tidal volume increased to 108 +/- 6% and 105 +/- 6%, respectively, of their premidazolam values; at the same time after administration of placebo, VE46 and tidal volume remained significantly depressed (between groups, P less than 0.005 for each variable). Thirty minutes later, these variables did not differ between groups, probably because the effects of flumazenil and midazolam were diminishing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859006 TI - The additive contribution of nitrous oxide to isoflurane MAC in infants and children. AB - The purpose of this study was to determine the contribution of nitrous oxide to isoflurane MAC in pediatric patients. MAC was determined in 47 infants and small children (mean ages 16.6 +/- 6.7 months) during isoflurane and oxygen anesthesia (n = 11) and isoflurane and nitrous oxide anesthesia (25% nitrous oxide [n = 12], 50% nitrous oxide [n = 12], and 75% nitrous oxide [n = 12]). After assigning patients to one of four groups, anesthesia was induced with increasing inspired concentrations of isoflurane in oxygen. After anesthetic induction and tracheal intubation, ventilation was controlled (carbon dioxide partial pressure = 32 +/- 5 mmHg), and nitrous oxide was added to the inspired gas mixture to achieve end expired nitrous oxide concentrations of 0, 25, 50, or 75%. Inspired and expired gas samples were obtained from a distal sampling port in the tracheal tube. The response to skin incision in each patient was assessed at a previously selected end-tidal concentration of isoflurane. The MAC of isoflurane was determined in each group using the up-and-down method described for evaluating quantal responses. The mean duration of constant end-tidal concentrations prior to skin incision was 14 +/- 7 min (range 6-46 min). The ratio of expired to inspired nitrous oxide and isoflurane concentrations during the period of constant end tidal concentrations was 0.96 +/- 0.01 and 0.93 +/- 0.03 respectively. The MAC of isoflurane in oxygen was 1.69 +/- 0.13 vol% (mean +/- standard deviation).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859007 TI - The neuromuscular effects of ORG9426 in patients receiving balanced anesthesia. AB - In searching for a nondepolarizing muscle relaxant with intermediate duration but more rapid onset of action than the presently available compounds, the neuromuscular and circulatory effects of ORG9426 were investigated in two studies in humans receiving fentanyl, droperidol, thiopental, and nitrous oxide-oxygen anesthesia. Eighty patients, randomly assigned to one of four groups of 20 each, received 0.12, 0.16, 0.20, or 0.24 mg/kg ORG9426. In the first study, the doses (in milligrams per kilogram) of ORG9426 that caused 50% (ED50), 90% (ED90), or 95% (ED95) neuromuscular block were determined by the individual dose-response method; they were 0.170, 0.268, and 0.305 mg/kg, respectively. In the second study, after induction of anesthesia, patients received 0.6 mg/kg (about 2 x ED95) of ORG9426, either in a single bolus (group 1) or in two unequal (0.1 and 0.5 mg/kg) increments 4 min apart (group 2). After the administration of 0.6 mg/kg ORG9426, maximal neuromuscular block developed in 1.5 +/- 0.12 min in group 1 and in 1.2 +/- 0.14 min in group 2. Patients tracheas were intubated after development of the maximal neuromuscular effect of the intubating dose and after the recording of heart rate and systolic and diastolic blood pressure. There was no difference in the clinical duration of the intubating doses, which were 40.0 +/- 3.2 (15-73) min in group 1 and 39.3 +/- 2.4 (19-57) min in group 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859008 TI - Effect of propofol on the incidence of postoperative vomiting after strabismus surgery in pediatric outpatients. AB - Vomiting is a common problem after strabismus surgery in pediatric outpatients. We compared the effects of propofol with and without N2O and droperidol to the effects of a conventional regimen consisting of halothane-N2O-droperidol on the recovery characteristics and the incidence of postoperative emesis after strabismus surgery in 120 ASA physical status 1 or 2 children. After induction of anesthesia with halothane-N2O, patients were randomly assigned to one of four groups. Group A (control) received halothane, 66% N2O, and droperidol 75 micrograms.kg-1; group B, propofol 2 mg.kg-1 bolus followed by infusion of 160 microgram.kg-1.min-1; group C, propofol (as in group B) and 66% N2O; and group D, propofol (as in group B), 66% N2O (as in group C), and droperidol 75 micrograms.kg-1. Patients in group B had more episodes of intraoperative oculocardiac reflex responses than patients in group A, but had shorter times to extubation, oral intake, ambulation, and discharge, as well as a lower incidence of postoperative emesis (P less than 0.05). The addition of N2O to the propofol anesthetic regimen (group C) was associated with an increased incidence of emesis (P less than 0.05), whereas the addition of droperidol to the propofol-N2O regimen (group D) did not affect the incidence of emesis compared to the other three groups. We conclude that maintenance of anesthesia with a total intravenous regimen using propofol results in a more rapid recovery and less postoperative emesis than with a halothane-N2O-droperidol regimen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859009 TI - Oral clonidine blunts the heart rate response to intravenous atropine in humans. AB - Clonidine, recently introduced into anesthesia practice, may cause bradycardia. Whether this bradycardia is reversible with atropine is not known. Accordingly, we studied heart rate (HR) responses to intravenous atropine in 80 patients assigned randomly to either a control group, who received no medication (n = 20), or a clonidine group, who received oral clonidine of approximately 1.2 micrograms.kg-1 (n = 20), 2.5 micrograms.kg-1 (n = 20), or 5 micrograms.kg-1 (n = 20). All patients received incremental doses of atropine, 2.5, 2.5, and 5 micrograms.kg-1, at 2-min intervals (total dose 10 micrograms.kg-1). Positive chronotropic response to the cumulative atropine dose of 10 micrograms.kg-1 was attenuated significantly only in patients given clonidine 5 micrograms.kg-1 (7 +/ 1 beats per min, mean +/- standard error) when compared with those given smaller doses of clonidine (15 +/- 2, 16 +/- 2 beats per min) or no clonidine (19 +/- 2 beats per min) (P less than 0.05). To determine whether HR hyporesponsiveness to atropine induced by clonidine can be overcome by a larger dose of atropine, the authors studied 30 additional patients given clonidine 5 micrograms.kg-1 or no medication. In all patients not receiving clonidine (n = 15), HR increased by more than 20 beats per min when atropine of 15 micrograms.kg-1 was administered, whereas in only 5 patients (33%) receiving clonidine did the HR increase by 20 beats per min after atropine 15 micrograms.kg-1 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859010 TI - Absorption and bioavailability of oral transmucosal fentanyl citrate. AB - Oral transmucosal fentanyl citrate (OTFC) is a novel, noninvasive dosage form of fentanyl used to provide children and adults with sedation, anxiolysis, and analgesia. In order to determine the bioavailability and absorption of fentanyl from OTFC, 12 volunteers were given intravenous fentanyl citrate or OTFC 15 micrograms/kg on each of two occasions. On a third occasion, the authors assessed oral administration (gastrointestinal absorption) by giving eight of the same volunteers the same dose of a solution of fentanyl citrate to swallow. In each study, arterial blood samples were taken over 24 h for analysis of plasma fentanyl. After intravenous (iv) administration of fentanyl, clearance (mean +/- standard deviation) was 0.67 +/- 0.15 l/min; volume of distribution at steady state was 287 +/- 79 l; and the terminal elimination half-life was 425 +/- 102 min. Peak plasma concentrations of fentanyl were higher (3.0 +/- 1.0 vs. 1.6 +/- 0.6 ng/ml, P = 0.01) and occurred sooner (22 +/- 2.5 vs. 101 +/- 48.8 min, P = 0.003) after OTFC than after oral solution administration. Plasma concentrations of fentanyl after OTFC decreased rapidly, to less than 1.0 ng/ml within 75-135 min after the beginning of administration. Peak absorption rate was greater (11.1 +/- 4.3 vs. 3.6 +/- 2.1 micrograms/min, P = 0.004) and occurred much sooner after OTFC than after oral solution administration (19 +/- 2.6 vs. 87.5 +/- 38.1 min, P = 0.001). Systemic bioavailability was greater after OTFC administration than after the oral solution (0.52 +/- 0.1 vs. 0.32 +/- 0.1, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859011 TI - A system model for closed-circuit inhalation anesthesia. II. Clinical validation. AB - Recently, we described a basic model and its more elaborate variants to predict the uptake and distribution of inhalational anesthetics during closed-circuit anesthesia. As an initial clinical validation of the linear, continuous, 14 compartment basic model, the current study examined its predictive performance in 50 patients by comparing quantitatively the predicted and the measured alveolar concentration-time profiles after bolus injections of liquid isoflurane into the closed system during mechanical ventilation. The two versions of the model studied differed in the size of their peripheral shunt, as 0% (version A) and 16% (version B) of the cardiac output. A total of 15,744 alveolar concentrations of isoflurane (one per 10s period) were measured by mass spectrometry. For each measured concentration we used computer simulations of version A and version B to calculate a predicted concentration for both versions. For each patient we calculated the bias (indicating over- or underprediction) and the scatter of the prediction errors (indicating the typical error size). The bias and the scatter of the prediction errors, both given as mean (and standard deviation), were 2.25 (13.59) and 12.51 (5.84)% for version A and 12.00 (14.97) and 14.12 (6.54)% for B. Version A performed better than B: both the bias (P = 0.008) and the scatter (P less than 0.0001) were closer to zero for A. Logistic regression analysis showed for version A that scatter, but not bias, increased with age (P = 0.002). Gender, body mass index (weight x height-2), and number of injections per hour did not influence scatter or bias.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859012 TI - Dose-response for atropine and heart rate in infants and children anesthetized with halothane and nitrous oxide. AB - The dose recommendations for atropine in anesthetized children vary, and the dose response for heart rate has not been defined. We determined the dose-response for atropine and heart rate in 181 healthy children anesthetized with halothane and nitrous oxide. After induction of anesthesia, atropine in a dose of 5, 10, 20, 30, or 40 micrograms.kg-1 was administered by rapid intravenous infusion of each subject. The effects of atropine on heart rate, heart rhythm, and systolic blood pressure were compared among dosage groups, and a dose-response curve for peak heart rate was constructed. The effects of atropine were compared also between younger and older subjects. For the group of all 181 subjects, atropine increased heart rate in a dose-related manner up to 30 micrograms.kg-1. Fifty percent maximal response corresponded to 9 micrograms.kg-1, and 90% maximal response corresponded to 26 micrograms.kg-1. Some subjects had nonsinus supraventricular rhythms before atropine, but none had nonsinus rhythm after atropine except after the smallest dose, 5 micrograms.kg-1. Systolic blood pressure increased significantly after all doses of atropine except 5 mu.kg-1. Subjects less than 6 months old had higher control and peak heart rates than did subjects greater than or equal to 2 yr old, but the older subjects had greater change in heart rate after atropine. For subjects greater than or equal to 2 yr old, all doses of atropine produced a significant increase in heart rate. The same was true for younger subjects, less than 6 months old, except that 5 micrograms.kg-1 did not increase heart rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859013 TI - The effects of local anesthetics and epinephrine on rat sciatic nerve blood flow. AB - The effects of topical application of local anesthetics on peripheral nerve blood flow (NBF) were studied in the rat sciatic nerve. Sciatic NBF was measured by laser doppler in 45 adult female Sprague-Dawley rats (90 nerves) after topical application of 25 microliter lidocaine and epinephrine, alone and in combination (lidocaine plus epinephrine), as well as bupivacaine, tetracaine, and normal saline, and studied in a randomized, blinded experimental design. NBF changes produced by lidocaine were dose-dependent. Compared with that for saline, blood flow reduction for lidocaine 0.5% was not significant, but it was significant for lidocaine 1.0% at 2-5 min and for lidocaine 2.0% at all time periods after 1 min (P less than 0.05). Maximum reduction was seen at all concentrations by 5 min after application. Average blood flow reduction at 5 min was 7% for lidocaine 0.5%, 12% for lidocaine 1.0% and 18% for lidocaine 2.0%. Epinephrine also produced dose-dependent changes in NBF. Epinephrine 2.5 micrograms/ml produced a transient 20% increase in NBF lasting 2-3 min (P less than 0.05), followed by a return to baseline. Epinephrine 5.0 micrograms/ml and epinephrine 10.0 micrograms/ml produced reductions of 20% and 35%, respectively (P less than 0.05), which lasted throughout the study. The effects of each of the three concentrations were significantly different from the others. The combination of lidocaine plus epinephrine resulted in synergistic reduction of NBF for all drug concentrations (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859014 TI - Direct vasodilation by sevoflurane, isoflurane, and halothane alters coronary flow reserve in the isolated rat heart. AB - Direct vasodilation of coronary resistance vessels by anesthetics may reduce coronary flow reserve and interfere with myocardial flow-metabolism coupling. This study was performed to evaluate the potential for the halogenated anesthetic agents sevoflurane, isoflurane, and halothane to alter the regulation of coronary flow via a direct action on coronary resistance vessels. Coronary flow and flow reserve were measured in the quiescent isolated perfused rat heart at anesthetic concentrations between 0 and 3 x MAC. In order to minimize anesthetic-induced secondary changes in coronary resistance, constant coronary perfusion pressure was maintained; the left ventricular cavity was vented; and tetrodotoxin was used to achieve cardiac arrest. These conditions permitted the dissociation of direct anesthetic actions from indirect regulatory processes affecting coronary vascular resistance (CVR). Coronary flow reserve was defined as the difference between coronary flow prior to and during administration of a maximally vasodilating dose of adenosine. Each anesthetic significantly reduced the magnitude of both CVR and coronary flow reserve in a concentration-dependent manner. Sevoflurane reduced coronary flow reserve significantly less than did halothane and isoflurane. At high concentrations (3.0 x MAC), coronary flow reserve was abolished by halothane and was decreased to near zero by isoflurane; however, flow reserve was reduced only 48% from control by sevoflurane. This difference among anesthetics is explained primarily by variations in the magnitude of direct coronary vasodilation produced by each anesthetic, rather than by effects on maximal vasodilator capacity. These data show that sevoflurane's intrinsic vasodilator action on coronary resistance vessels differs substantially from that of halothane and isoflurane. PMID- 1859015 TI - Lack of protection by the N-methyl-D-aspartate receptor blocker dizocilpine (MK 801) after transient severe cerebral ischemia in the rat. AB - Glutamate is an important factor in the mechanisms of neuronal damage following cerebral ischemia. Blockade of one type of glutamate receptor, the N-methyl-D aspartate (NMDA) receptor, decreases brain infarct size in experimental models of permanent focal ischemia, but protection in models of transient reversible ischemia is ambiguous. We investigated the effect of the noncompetitive NMDA receptor antagonist dizocipiline (MK-801) on neuronal damage in the CA1 region of the rat hippocampus, using two models of reversible cerebral ischemia: 10 or 15 min of bilateral common carotid occlusion combined with hypotension, or 6-8.5 min of cardiac arrest. Histopathologic evaluation of neuronal damage was performed 7 days after the ischemic insults. Thirteen groups of rats (a total of 129 animals) were treated with saline or dizocilpine in single or multiple doses ranging from 0.1 to 5 mg.kg-1, given intravenously or intraperitoneally prior to and/or after the ischemic insult. In none of the dizocilpine-treated groups could neuronal protection be demonstrated in the CA1 region of the septal as well as dorsotemporal hippocampus, compared to a corresponding saline-treated group. We conclude that systemically administered noncompetitive NMDA receptor antagonists do not provide a marked protection against neuronal damage after a transient period of severe forebrain ischemia. PMID- 1859016 TI - The use of immobilized protamine in removing heparin and preventing protamine induced complications during extracorporeal blood circulation. AB - Heparin, currently used in extracorporeal blood circulation procedures, may lead to hemorrhagic complications. Protamine, used for reversal of heparin-induced anticoagulation at the end of such procedures, can cause adverse hemodynamic responses. To prevent both types of complications, we have developed a reactor device containing immobilized protamine (i.e., a protamine bio-reactor) that can be placed at the distal end of the circuit, thus providing simultaneous extracorporeal heparin removal and protamine treatment. In preliminary in vivo studies involving dogs at a blood flow of 100 ml/min, the bio-reactor removed about 50% of the administered dose of heparin (i.e., 100 units/kg) in 10 min. While rapid injection of protamine in dogs anticoagulated with heparin produced a transient and significant (P less than 0.005) decreases in systemic arterial blood pressure (-39.5 +/- 9.2 mmHg), cardiac output (-1.59 +/- 0.23 L/min), and mixed venous oxygen saturation (-7.5 +/- 1.3%) and increases in pulmonary artery systolic (+12.7 +/- 4.4 mmHg) and diastolic pressures (+10.0 +/- 3.6 mmHg), the use of the protamine bio-reactor did not elicit any statistically significant change in any of the variables measured. Hemolysis was not significant, as reflected by a statistically insignificant change of the animals' red blood cell counts, hematocrits, and total hemoglobin values. In addition, hemolytic complement was found to be reduced only by 10% in animals with the protamine bio reactor, whereas it was reduced rapidly by 20% in animals receiving intravenous protamine administration and progressively by 20% in control animals with a sham reactor that contained no protamine. Furthermore, the use of the protamine bio reactor also significantly reduced the protamine-induced transient thrombocytopenic and granulocytopenic responses. The white blood cell counts and platelet counts decreased to 87.7 +/- 7.5 and 83.3 +/- 5.0% of baseline, respectively, in dogs with the protamine bio-reactor compared to 35.5 +/- 14.3 and 32.1 +/- 8.1% of baseline in dogs receiving intravenous protamine. The protamine bio-reactor may provide a unique means to simultaneously control both heparin- and protamine-induced complications. PMID- 1859017 TI - Anesthetics and automaticity in latent pacemaker fibers. II. Effects of halothane and epinephrine or norepinephrine on automaticity of dominant and subsidiary atrial pacemakers in the canine heart. AB - Knowledge of anesthetic effects on the automaticity of dominant and subsidiary cardiac pacemakers is fundamental to an understanding of mechanisms of arrhythmia during anesthesia, as well as to the management of patients with sinus node dysfunction or atrioventricular (AV) conduction block. Among potential pacemakers of the heart are subsidiary atrial pacemakers (SAP), which are located outside the classic sinoatrial (SA) node region but still within the right atrium. SAP have a higher inherent rate of automaticity than AV junctional pacemakers, may contribute to a multicentric atrial pacemaker complex, and can control the rhythm of the heart when the SA node is absent or inhibited. How halothane, epinephrine (E), or norepinephrine (NE), alone or in combination, would affect the relation between the automaticity of the SA node and SAP was tested using an isolated, perfused canine right atrial preparation (n = 78). This preparation was perfused via the SA node artery with Krebs' solution (36.0 +/- 0.5 degrees C) equilibrated with 97% oxygen-3% carbon dioxide. Delivered concentrations of halothane of 1 or 2% corresponded to measured perfusate concentrations of 0.50 +/- 0.02 or 0.80 +/- 0.04 mM in experiments with E (n = 24) and 0.45 +/- 0.02 or 0.75 +/- 0.04 mM in experiments with NE (n = 54). E or NE perfusate concentrations were 1, 2, and 5 micrograms/l or 2, 5, and 10 micrograms/l, respectively. To determine the site of earliest activation (SEA), extracellular recordings were made from the SA node region and distal sites (approximately 1, 2, and 3 cm) along the sulcus terminalis, the previously reported locations of SAP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859018 TI - Anesthetics and automaticity in latent pacemaker fibers. III. Effects of halothane and ouabain on automaticity of the SA node and subsidiary atrial pacemakers in the canine heart. AB - Atrial tachyarrhythmias are a common manifestation of digitalis toxicity. Such arrhythmias could be due to enhanced automaticity of subsidiary atrial pacemakers (SAP) compared to the sinoatrial (SA) node. Halothane is known to oppose digitalis-induced ventricular arrhythmias. Its effect on digitalis-caused atrial arrhythmias is unknown. Therefore, we tested two hypotheses, as follows. First, increasing ouabain concentrations would enhance automaticity of SAP compared to the SA node and that such enhanced automaticity could explain digitalis-caused atrial tachyarrhythmias. Second, halothane would oppose such enhanced automaticity of SAP, thereby opposing digitalis-caused atrial tachyarrhythmias. A canine right atrial preparation was perfused via the SA node artery with Krebs' solution (36.0 +/- 0.5 degrees C) equilibrated with 97% oxygen-3% carbon dioxide. Four bipolar extracellular electrodes recorded the site of earliest activation (SEA), which in this preparation could be the SA node or increasingly remote sites of SAP approximately 1, 2, and 3 cm distal to the SA node along the sulcus terminalis. Pacemaker shifts to SAP during exposure to drugs were scored for magnitude of shift as 1, 2, or 3 depending on which SAP site was the SEA. Magnitude scores were summed for each test condition and normalized by dividing the total number of preparations tested. Preparations (n = 48) were exposed to 1 or 2% halothane (perfusate concentrations of 0.51 +/- 0.01 or 0.79 +/- 0.03 mM, respectively) and/or to low- or mid-therapeutic (2.5 or 5 x 10(-8) M) or borderline toxic ouabain (1 x 10(-7) M). Normalized magnitude scores were not significantly different from zero (control value) with any halothane or ouabain concentration alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859019 TI - Comparative effects of halothane, isoflurane, and sevoflurane on the liver with hepatic artery ligation in the beagle. AB - Recently, there has been increasing interest in the alterations in splanchnic and hepatic circulation and preservation of hepatic oxygenation and function during anesthesia and surgery. However, the effects of volatile anesthetics under a condition of marginal hepatic oxygen supply are not well understood. Using a crossover design, we therefore studied the effects of equianesthetic concentrations (1.5 MAC) of halothane, isoflurane, and sevoflurane on hepatic oxygenation and function in nine beagles in which the hepatic artery had been ligated. Portal blood flow was measured by an electro-magnetic flow meter. Hepatic function was assessed by indocyanine green elimination kinetics. While cardiac output and mean arterial pressure were greater during halothane anesthesia than during isoflurane and sevoflurane anesthesia, portal blood flow and hepatic oxygen supply were significantly less during halothane and sevoflurane anesthesia than during isoflurane anesthesia. With regard to hepatic oxygen uptake, there was a significant difference between halothane (2.7 +/- 1.2 ml.min-1 x 100 g-1) and sevoflurane (3.7 +/- 2.0 ml.min-1 x 100 g-1; P less than 0.05). Consequently, the hepatic oxygen supply/uptake ratio and the hemoglobin oxygen saturation and oxygen partial pressure in hepatic venous blood during sevoflurane anesthesia were significantly less than they were with the other anesthetics. Indocyanine green clearance was better preserved during sevoflurane anesthesia (39.7 +/- 12.0 ml.min-1) than during halothane anesthesia (30.9 +/- 8.4 ml.min-1; P less than 0.05). We conclude that sevoflurane is accompanied by a smaller oxygen supply/uptake ratio than is halothane and isoflurane, while it preserves hepatic function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859020 TI - Arterial tonometry for noninvasive, continuous blood pressure monitoring during anesthesia. AB - Arterial tonometry is a technique used to measure arterial blood pressure noninvasively. The authors developed a new tonometer system containing an array of 15 piezoresistive pressure transducers, a mechanical positioning system, signal conditioning and multiplexing electronics, and a display and control console. The authors evaluated the accuracy, reliability, and clinical acceptability of this system by comparing tonometric blood pressure measurements with intraarterial blood pressure measurements in 60 anesthetized patients. Blood pressure was measured intraarterially in either the right or left radial artery by a Gould P23XL calibrated transducer, whereas blood pressure was measured by tonometer at the radial artery of the other arm. The tonometric waveform was similar to the intraarterial waveform. Simultaneous tonometer and intraarterial systolic blood pressures of the 60 patients (3,036 data sets) had an overall regression coefficient, r = 0.97, and an equation, regression equation = 0.95X + 5.8. Similar values were obtained for mean and diastolic pressures. Regression analyses of the paired tonometric and intraarterial blood pressure values showed good correlations in both sexes and in ages ranging from 8 to 82 yr (r = 0.94 0.97). Mean absolute values of error (precision) for the systolic, mean, and diastolic measurements did not differ significantly among the five systolic, five mean, and four diastolic pressure groups and ranged from 3.6 to 6.6 mmHg, with negligible bias, with intraarterial pressure used as the reference. Bias for the various pressure groups was small: -0.9-3.6 mmHg for systolic; -3.0-0.7 mmHg for mean; and -2.1-4.5 mmHg for diastolic. The "limits of agreement" (mean difference +/- two standard deviations) were within an acceptable range for clinical anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859021 TI - Observation of spinal canal and cisternae with the newly developed small diameter, flexible fiberscopes. AB - Small-diameter (0.5-, 0.9-, and 1.4-mm) flexible fiberscopes were developed for visual diagnosis of spinal canal diseases. The fiberscopes were introduced via a Tuohy needle into the subarachnoid and epidural spaces of ten patients with various pain syndromes. Clear visualization of the subarachnoid space was achieved using the fiberscopes. The epidural space could be visualized only during withdrawal of the fiberscope. In five cases, the fiberscope could be advanced up to the level of the cisternae without causing the patient any discomfort. A slight headache and transient fever were noted after the examination in five and two cases, respectively, but no other complications occurred. Interestingly, preexisting pain diminished (two cases) or disappeared (one case) after the myeloscopy in three of five cases in which the myeloscopy revealed aseptic adhesive arachnoiditis. Further studies should be carried out to evaluate the usefulness of this technique. PMID- 1859022 TI - A system model for closed-circuit inhalation anesthesia. I. Computer study. AB - Developing a custom computer program to simulate the uptake, distribution, and elimination of inhalational anesthetics allows the anesthesiologist to address specific problems, but extensive skills are required to translate the involved processes first into a set of mathematical equations and then into a satisfactory computer program. The first step is often facilitated by solutions offered in the literature. The second step demands computer proficiency that is often not available, but this problem can be obviated by means of a special-purpose simulation language (SPSL). We therefore constructed a model for closed-circuit inhalation anesthesia with the aid of the block-structured SPSL TUTSIM. Noticeable differences with previous models are that the linear, 14-compartment basic model does not assume a constant alveolar concentration and mimics circulation times through the use of blood pools. Advanced features of the SPSL were used to develop variants of the basic model to simulate feedback-controlled isoflurane administration, nitrous oxide uptake, and the impact of a nonlinearity by incorporating the effect of enflurane on cardiac output. Two variants were concatenated to form a multiple model showing the concentration and second-gas effects. The model was capable of reproducing the anesthetic uptake from previous experimental studies for nitrous oxide. After its validation for other anesthetic agents, the model can be used for clinical, teaching, and research purposes. The SPSL freed the authors from the problems associated with computer programming and allowed them to concentrate on the structure of the model. PMID- 1859023 TI - Unintentional arterial catheterization and bupivacaine toxicity associated with continuous interscalene brachial plexus block. PMID- 1859024 TI - Phenol motor point blocks in children: plasma concentrations and cardiac dysrhythmias. PMID- 1859025 TI - Epidural analgesia in patients with congenital lumbosacral spinal anomalies. PMID- 1859026 TI - Postoperative apnea in a full-term infant. PMID- 1859027 TI - Propofol: bolus induction plus continuous infusion in a patient with Duchenne muscular dystrophy. PMID- 1859028 TI - No coronary dilation: no coronary steal. PMID- 1859029 TI - Inotropic effect of amrinone. PMID- 1859030 TI - Peripheral nerve injury and automatic blood pressure measurement. PMID- 1859031 TI - A cause for hemodynamic instability during hepatic tumor resection. PMID- 1859033 TI - Percutaneous puncture of the internal jugular vein using continuously transduced pressure. PMID- 1859032 TI - Burns associated with pulse oximetry during magnetic resonance imaging. PMID- 1859034 TI - Interpretation of pollen counts. PMID- 1859035 TI - Difficult hand dermatitis. PMID- 1859037 TI - Effectiveness of an acaricide in management of house dust mite allergy. AB - The effects of treating the environment of 25 dust mite-allergic patients with an acaracide are reported. Remarkable symptomatic improvements in asthma, eczema, or rhinitis were observed. Many patients could reduce or stop medication, and these benefits have persisted for up to a year after using Acarosan once only. Relapse of symptoms following exposure to untreated dusty environments was observed on many occasions confirming that the improvements were due to removal of the mite allergen. PMID- 1859036 TI - Effect of maternal immunotherapy on immediate skin test reactivity, specific rye I IgG and IgE antibody, and total IgE of the children. AB - The effect of specific immunotherapy during pregnancy was studied in 14 children, 3 to 12 years after delivery. Fourteen additional children from the same allergic mothers, in whom immunotherapy was not given during the pregnancy, served as controls. The immediate skin test response to grass allergens of the children of mothers given immunotherapy. Levels of rye I IgG and total IgE were lower in the sera of children born to mothers who received immunotherapy (not statistically significant) than their control cohorts. Paired cord blood and maternal blood samples drawn at delivery showed similar levels of rye I IgG, indicating that blocking antibody freely crosses the placenta. This evidence indicates that immunotherapy during pregnancy may have an inhibitory effect on immediate skin reactivity to grass allergens in some of the offspring. Whether tolerance to other allergens can be induced in children by maternal immunotherapy remains to be determined. PMID- 1859038 TI - The skier's nose: a model of cold-induced rhinorrhea. AB - Cold-induced rhinorrhea (CIR) is a commonly experienced discomfort not previously addressed in the medical literature. In a 2-part study, we assessed the prevalence and described the characteristics of CIR and evaluated the efficacy of an anticholinergic nasal spray in its treatment. In Part 1, 90 general medical patients at a ski resort clinic were asked to describe their symptoms associated with cold exposure. Ninety-six percent reported some degree of CIR; 48% reported moderate to severe CIR. Fifty percent had some degree of nasal congestion and 33% reported sneezing. Allergic and nonallergic patients described similar degrees of rhinorrhea. In Part 2, 14 ski patrollers were given atropine sulfate in saline (AS/S) nasal spray before cold exposure in double-blinded placebo (P) controlled crossover fashion. Ninety-two percent noted improvement of CIR with AS/S and 8% experienced no change. None of the subjects noted worsening of symptoms, however, one subject reported excessive dryness at the AS/S concentration used. All 14 subjects receiving P experienced no change in CIR. We conclude that CIR is a distinct clinical syndrome frequently seen with cold temperature exposure, presenting primarily as rhinorrhea and sometimes involving nasal congestion and sneezing. Pretreatment with a 0.005% solution AS/S can effectively block CIR with only minimal short-term side effects. PMID- 1859039 TI - Asteraceae aeropollen of the western United States Gulf Coast. AB - Volumetric air sampling was performed near Corpus Christi, Texas during 1988 and supplemented with data from 1987 and 1989. Frequencies of captured pollen grains of Parthenium hysterophorus, Ambrosia and allied genera, Helianthus, and other Asteracea were examined. Asteraceous aerospora in 1988 accounted for 22.1% of all pollen found, of which 83.4% were pollen of Ambrosia, 12.4% of Parthenium, and the remainder (4.1%) representative of other genera. Capture of native Ambrosia species and P. hysterophorus peaked in September and October in 1987 and 1988, but Parthenium pollen was also found year round with a smaller secondary peak during May, 1988 and 1989. In the winter a different Ambrosia pollen was captured which compared with A. hispida found in the Yucatan Peninsula and southern Florida at a time when no ragweed was flowering in the vicinity of Corpus Christi. Such a pollen capture probably represents long distance dispersal (ca. 600 miles, 965 km) on strong easterly to southerly prevailing winds. Pollen capture occurred most frequently during daylight hours when percent relative humidity was lower and near midnight when inversions occur. Comparison of pollen capture with meteorologic data demonstrated that photoperiodic responses probably account for the initiation and termination of Ambrosia flowering, and to some extent that of Parthenium, and not sharply lowered temperatures or frost for ending pollen release. Previous plant surveys have shown that P. hysterophorus is more common in the Corpus Christi area than species of Ambrosia, or any other Asteraceae, even though ragweed pollen capture proved 6.9 times greater. This disparity is most likely due to limited long distance dispersal of Parthenium pollen, less pollen produced per another, and a less developed mechanism of wind pollination (passive dispersal or amphiphilous). Since both Parthenium and Ambrosia are significant allergenic plants, correlations between airborne pollen of Parthenium and allergic potential suggest that a prolonged pollination season and perhaps increased allergenicity of unique Parthenium pollen proteins allow Parthenium to be a major allergen despite significantly less ambient pollen. PMID- 1859040 TI - Aeropollen of weeds of the western United States Gulf Coast. AB - Volumetric air sampling was performed near Corpus Christi, Texas during all of 1988. The most significant weeds releasing airborne pollen, besides the Asteraceae, were the Amaranthaceae and Chenopodiaceae at 14.8% of total pollen captured, which peaked in September and October. Greater pollen capture (74%) occurred from a peak at 11 PM at a time when inversions are frequent to 9 AM than during the period from late morning to 9 PM. Frequency of amaranth-chenopod pollen capture in the western Gulf Coast region showed no relationship with frequencies along the northern and eastern Gulf Coast nor in eastern North America generally, but rather with western North America where these grains have also been sampled at high levels. As in the West, therefore, amaranth-chenopod aeropollen is sufficiently frequent to be a major source of allergens in the western Gulf Coast region. Other weedy plants, Cannabis/Humulus, Rumex, and the Urticaceae (Parieteria/Urtica) each account for only about 1% of the total annual pollen shed, and consequently they are not nearly as potentially relevant here in pollinosis as are the amaranth-chenopods and Asteraceae. Plantago pollen is very infrequently sampled (less than 0.1%) even though several species are common in the area. Acalypha is newly reported as releasing airborne pollen, a genus related to Mercurialis known to release allergenic pollen in Europe. PMID- 1859041 TI - Current concepts in ocular allergy. AB - Ocular allergy is commonly encountered by the allergist, general physician, and ophthalmologist. Diagnosis can usually be made by history, especially a history of itching and an allergic background. The diagnosis can be confirmed by skin testing, in vitro testing, and conjunctival scrapings to look for eosinophils. Once the diagnosis is made, a decision can be reached as to whether treatment is necessary. Often, supportive treatment, or removal of the allergen is preferred. When pharmacologic treatment is necessary, it is advisable to choose a benign form of therapy such as topical vasoconstrictor-antihistamine eyedrops or cromolyn sodium. Topical steroids are rarely necessary and should be used with great caution since they can induce serious sight threatening complications. If topical steroids are required, the patient should be monitored by an ophthalmologist. PMID- 1859042 TI - Bronchial reactivity and allergy-promoting factors in monozygotic twins discordant for allergic rhinitis. AB - Bronchial reactivity was studied twice in eight monozygotic twin pairs discordant for allergic rhinitis with pollen hypersensitivity, during the winter season (all eight pairs) and during the pollen season (seven pairs). On both occasions, the allergic twins showed significantly higher reactivity than their nonallergic siblings. The results indicate that moderate allergic rhinitis is associated with increased bronchial reactivity. This increased reactivity is an acquired trait; however, bronchial reactivity is not constantly increased in pollen rhinitis and may be normal even during the pollen season. The symptoms of allergic rhinitis usually started in childhood before the separation of the siblings. We could not demonstrate any major differences in exposure to allergens or airway irritants between the siblings. The allergic twins tended to have lower birth weight and insufficient weight increase just after birth. PMID- 1859043 TI - Analysis of house dust mite-specific IgE, IgG4, and IgG antibodies during immunotherapy in asthmatic children. AB - House dust mite (Dermatophagoides pteronyssinus, DP) specific IgE, IgG4, and IgG antibodies were analyzed by Western blotting in 18 asthmatic children during the course of 2-years' allergen-specific immunotherapy. Although more than 50 protein bands could be identified in the crude mite extracts by SDS-PAGE, only eight of them elicited both IgE and IgG4 antibodies in most patients. The molecular weights were 110, 60, 55, 43, 33, 27, 16, and 14 kD, respectively. No antibodies against new antigens were induced after immunotherapy. There was a significant correlation between the intensity of reactive bands of Western blotting and RAST. IgG4 antibody was increased in 72% (13/18) of patients, but the simultaneous change in IgE varied. Analysis of allergen-specific IgE and IgG4 antibodies by Western blotting may provide a useful tool for evaluation of clinical response to immunotherapy. PMID- 1859044 TI - Comparison of three pretreatment protocols to prevent anaphylactoid reactions to radiocontrast media. AB - Three pretreatment regimens were compared for prevention of anaphylactoid reactions in 149 patients who previously had reacted to radiocontrast media (RCM) administration. From 1976 to 1980, 52 patients were treated with 50 mg of oral prednisone 13, 7, and 1 hour before and 50 mg intramuscular diphenhydramine 1 hour before procedures (group I). From 1980 to 1984, 48 patients received 300 mg oral cimetidine one hour before procedure in addition to the other regimen (group II). From 1984 to 1989, 49 patients received the three drugs and 25 mg oral ephedrine one hour before procedures (group III). Previous reactions were similar in each group, consisting of urticaria and/or angioedema in all patients, hypotension in some (groups I, 5; II, 6; III, 4), and wheezing in two (group I). Readministration of RCM was intraarterial (groups I, 18; II, 20; III, 20) or intravenous. Generalized reactions upon readministration of RCM occurred in 4 (8%) of group I and 3 (6%) of both groups II and III. All reactions consisted of urticaria and/or angioedema, were mild, and required no specific treatment. In a separate group of ten patients whose previous reactions to RCM were life threatening (shock), pretreatment was accompanied by a provocative dosing regimen. Two patients (20%) experienced systemic reactions that resulted in termination of the procedure. All our pretreatment regimens were equally effective; however, we favor a more comprehensive pretreatment protocol (regimen III) based upon our lack of demonstrated adverse effects and a possible therapeutic advantage as reported by other investigators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859045 TI - Growth and the nutritional status of nonsteroid-dependent asthmatic children. AB - Nonsteroid dependent children were evaluated to determine the effect of asthma on growth and nutritional status. No significant differences were observed for the growth of asthmatics and control groups. In addition, dietary records indicated asthmatics met or exceeded the recommended daily allowance for total calories and nutrients. PMID- 1859046 TI - Treatment of anaphylaxis. PMID- 1859047 TI - Neutrophils and adult respiratory distress syndrome: two interlocking perspectives in 1991. PMID- 1859048 TI - Tumor necrosis factor levels in serum and bronchoalveolar lavage fluid of patients with the adult respiratory distress syndrome. AB - Tumor necrosis factor (TNF) was measured antigenically and functionally in serum and bronchoalveolar lavage fluid (BAL) of patients with ARDS and those at high risk for ARDS. Of 22 patients with ARDS, 14 had sepsis or serious infection as the major clinical predisposition, and 10 of 20 high-risk patients had sepsis or serious infection. Mean levels of TNF in serum of patients with ARDS and high risk showed a trend toward elevation but were not significantly higher than mean serum levels in normal subjects. Mean levels of TNF in BAL of ARDS patients (242 +/- 126 pg/ml) were significantly higher than in normal subjects (9 +/- 5 pg/ml), p less than 0.05. Antigenic levels of TNF were undetectable in approximately half the patients with ARDS or the high-risk state. Levels of TNF in BAL appeared to be highest in the first day of ARDS. There appeared to be no relationship between levels of TNF in serum or BAL and subsequent mortality. However, serum levels of TNF were significantly higher in septic patients than in nonseptic patients, whereas this difference was not apparent in BAL. These results show that functional and antigenic elevations of TNF are present in BAL and perhaps in serum of patients with ARDS or with the high-risk state. PMID- 1859049 TI - Measurement of urinary desmosine by isotope dilution and high performance liquid chromatography. Correlation between elastase-induced air-space enlargement in the hamster and elevation of urinary desmosine. AB - The accuracy of methods employed to measure the elastin-specific crosslinks, desmosine (DES) and isodesmosine (IDES), has been called into question because contaminants in the urine may cause elevated values. In the present study urine samples were spiked with a known amount of [14C]DES and refluxed in 6 N HCl. Sephadex G-15 chromatography of the hydrolyzed urine employed to remove contaminants. DES and IDES were quantified by high performance liquid chromatography (HPLC) as well as by amino acid analysis. The amount of isotope recovered was used to determine losses during the overall procedure and the isotope dilution to calculate the amounts of endogenous DES and IDES originally present in the urine. Because similar values were obtained by both methods, the more rapid HPLC method was used for all succeeding analyses. In one experiment, the DES amounts in urine collected from hamsters for 3 days after intratracheal treatment with human neutrophil elastase (300 micrograms) or porcine pancreatic elastase (300 micrograms) were 0.212 +/- 0.012 (mean +/- SEM, two measurements on a single pool) and 0.816 +/- 0.005 (two measurements) microgram per hamster per day, respectively. Urine from control hamsters had a mean value of 0.074 +/- 0.008 (eight measurements) microgram per hamster per day. The HNE- and PPE treated hamsters had mean linear intercept values of 119 and 159% of control values, respectively, giving a positive correlation between increase in airspace size and elevation of urinary DES.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859050 TI - Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial. AB - Twenty-seven newly diagnosed patients with idiopathic pulmonary fibrosis (IPF) who were previously untreated for IPF were enrolled in a prospective, double blind, randomized, placebo-controlled study to compare the therapeutic effect of combined prednisone/azathioprine (n = 14) with prednisone plus placebo (n = 13). Prednisone was started at 1.5 mg/kg/day (not to exceed 100 mg/day) for the first 2 wk followed by a biweekly taper to a maintenance dose of 20 mg/day. Azathioprine was administered at a daily dose of 3 mg/kg (not to exceed 200 mg/day). The patients tolerated the use of azathioprine well with few associated side effects. Changes in lung function at 1 yr, as measured by resting alveolar arterial oxygen difference P[A-a]O2, FVC, and single breath diffusing capacity for carbon monoxide (DLCOSB), were all somewhat better in the azathioprine/prednisone group compared with the prednisone alone group, although none of these comparisons were statistically significant. Six of 14 (43%) patients randomized to prednisone plus azathioprine died during the 9-yr follow up period, compared with 10 of 13 (77%) patients randomized to prednisone plus placebo. A Cox model survival analysis shows a nonsignificant but potentially large survival advantage for azathioprine/prednisone (hazard ratio 0.48, with 95% confidence interval increasing from 0.17 to 1.38). When adjusted for age, the survival advantage of azathioprine/prednisone becomes marginally significant (hazard ratio 0.26, with 95% confidence interval increasing from 0.08 to 0.88; p = 0.02 by large sample approximation, p = 0.05 by randomization test). We conclude that combined prednisone and azathioprine is a safe and possibly effective regimen for the treatment of IPF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859051 TI - Distribution of silicotic collagenization in relation to smoking habits. AB - Controversy regarding the association between silicosis and lung cancer has been clouded by the fact that studies examining this association generally do not include information on smoking. A causal association between smoking and silicosis would seriously confound the association between silicosis and lung cancer. The current analysis assessed the association between silicosis and smoking using data on deceased white gold miners who underwent postmortem examination between 1976 and 1981. Smoking histories and exposure information were available. A subset analysis in a group of deceased miners for whom more detailed smoking and exposure information was available confirmed the findings of the larger analysis. Both analyses showed a slight inverse relationship between smoking and silicotic collagenization of the parenchyma and a stronger negative relationship between smoking and silicotic collagenization of the pleura, controlling for age and cumulative exposure to silica dust. No association between silicotic collagenization of the hilar glands and smoking was detected. The data should not be construed as advocating that workers exposed to silica dust should smoke. The hazards of cigarette smoking are likely to far outweigh the hazards of silicosis. The data suggest that the lack of smoking histories in studies of the association between silicosis and lung cancer probably does not seriously confound risk estimates. The distribution of silicotic collagenization in the lungs of smokers and nonsmokers is consistent with enhanced mucus interception, more central deposition in the lungs, and proportionally more lymphatic clearance to the hilum (as opposed to the pleura) of silica particles in smokers compared to nonsmokers. PMID- 1859053 TI - Severe community-acquired pneumonia. Epidemiology and prognostic factors. AB - Over a period of 4 consecutive yr, 92 nonimmunosuppressed patients (21 women and 71 men aged 53 +/- 16 yr, means = SD) with critical acute respiratory failure (PaO2/FiO2, 209 +/- 9 mm Hg) caused by severe community-acquired pneumonia were admitted to the respiratory intensive care unit (RICU) of a general hospital. The most frequent underlying clinical condition was chronic obstructive pulmonary disease (44 patients, 48%). A total of 56 patients (61%) required mechanical ventilation for a mean period of 10.7 +/- 12.5 days, 29 of them (52%) needing PEEP (9.9 +/- 3.8 cm H2O). A group of 23 (25%) patients had criteria of adult respiratory distress syndrome (ARDS). A causal microorganism was identified in 48 patients (52%), the two most frequent etiologies being Streptococcus pneumoniae (14, 15%) and Legionella pneumophila (13, 14%). Pseudomonas aeruginosa (5, 5%) was always associated with bronchiectasis. Mortality due to severe community acquired pneumonia was 22% (20 patients). According to univariate analysis, mortality was associated with anticipated death within 4 to 5 yr, inadequate antibiotic treatment before RICU admission, mechanical ventilation requirements, use of PEEP, FIO2 greater than 0.6, coexistence of ARDS, radiographic spread of the pneumonia during RICU admission, septic shock, bacteremia, and P. aeruginosa as the cause of the pneumonia. Further, recursive partitioning analysis selected two factors significantly related to the prognosis: the radiographic spread of the pneumonia during RICU admission and the presence of septic shock.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859052 TI - Prospective study of pulmonary function and lung cancer. AB - The role of pulmonary function as an independent predictor of lung cancer risk was studied in a community-based cohort of 6,317 Japanese-American men who were aged 45 to 68 at the time of examination. After a follow-up period of about 22 yr, 172 incident cases of lung cancer were identified. The percentage of the predicted FEV1 was inversely related to lung cancer (p value for trend = 0.01) after adjustment for age and cigarette smoking history. The subjects in the lowest quartile of pulmonary function (% predicted FEV1 less than 84.5) had a relative risk of 2.1 (95% confidence interval = 1.3 to 3.5) for lung cancer compared with subjects in the highest quartile (% predicted FEV1 = 103.5+). For the 84 cases with a squamous or small cell histologic type of lung cancer, the subjects in the lowest quartile had a relative risk of 2.5 (95% Cl = 1.2 to 5.6) compared with subjects in the highest quartile of pulmonary function. For the 84 patients with lung cancer whose tumors were located within 4 cm of the pulmonary hilum, the subjects in the lowest quartile had a relative risk of 4.0 (95% Cl = 1.7 to 9.7). The results suggest that impaired pulmonary function in a community based population is a predictor of lung cancer. PMID- 1859054 TI - Combined APACHE II score and serum lactate dehydrogenase as predictors of in hospital mortality caused by first episode Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. AB - We retrospectively analyzed data from 75 hospitalized patients with a first episode of Pneumocystis carinii pneumonia to compare the ability of four parameters, including admission serum albumin, serum lactate dehydrogenase (LDH), alveolar-arterial oxygen gradient, and the APACHE II score, to predict mortality and response to initial antipneumocystis therapy. The eight patients who died due to pneumocystosis and the 12 who failed initial antipneumocystis therapy had significantly higher admission mean APACHE II scores and serum LDH levels and lower mean serum albumin levels than did the 65 who survived and the 61 who responded to initial therapy (p less than 0.05 for each). Differences in mean alveolar-arterial oxygen gradients were not statistically significant with respect to survival or response to initial therapy. In a stepwise discriminant analysis of parameters associated with mortality, APACHE II score and LDH level were statistically significant (p less than 0.0001 for each). In a stepwise discriminant analysis of parameters associated with response to initial therapy, APACHE II score and LDH level were again statistically significant (p less than 0.0001, respectively). The addition of the alveolar-arterial oxygen gradient and serum albumin level did not further increase the predictive ability of the discriminant analyses. When analyzed alone, neither the alveolar-arterial oxygen gradient nor the serum albumin were statistically significant in each discriminant analysis. The APACHE II score combined with the serum LDH may be more useful than other parameters, singly or combined, to more closely match patients with regard to severity of illness due to first episode Pneumocystis carinii pneumonia when comparing experimental new therapies with standard agents. PMID- 1859055 TI - Reduction in the incidence of acute bronchitis by an oral Haemophilus influenzae vaccine in patients with chronic bronchitis in the highlands of Papua New Guinea. AB - Following the administration of a standardized questionnaire, 62 adult patients with chronic bronchitis were enrolled into a double-blind controlled trial of an oral killed Haemophilus influenzae vaccine in the highlands of Papua New Guinea. A 3-day course of vaccine or placebo was given monthly for 3 consecutive months. Participants were monitored weekly over 12 months for acute exacerbations; early morning sputum specimens were collected monthly and during acute exacerbations. Density of colonization by H. influenzae and H. parainfluenzae was determined by standard quantitative and semiquantitative techniques, and the latter method (quadrant score) was used to determine the density of growth of pneumococci. A total of 30 patients received vaccine and 32 placebo. The incidence rate of acute bronchitis in the vaccine group (0.011 episodes/person-weeks) was significantly lower than that in the placebo group (0.021 episodes/person-weeks), but there was no difference between the two groups in the incidence rates of more severe disease. Vaccine efficacy was maximal at times of peak incidence of disease. There was no evidence of a decline in vaccine efficacy for acute bronchitis over the 12-month follow-up period. The number of viable H. influenzae in the sputum declined in both vaccine and placebo groups over the 12-month follow-up period. The average concentration of H. influenzae in the vaccine group fell below that in the placebo group within 1 to 2 months after first immunization and remained so for 12 months, although the difference between the two groups narrowed during the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859056 TI - Predictive value of oropharyngeal cultures for identifying lower airway bacteria in cystic fibrosis patients. AB - Identifying lower respiratory pathogens in young, non expectorating cystic fibrosis (CF) patients has been problematic. Bronchial secretions are difficult to obtain, and little is known about lower airway flora in these patients. We collected simultaneous bronchial and oropharyngeal specimens in 43 CF patients in optimal respiratory status, including both expectorating (17) and nonexpectorating (26) patients, to determine the predictive value of oropharyngeal cultures for identifying lower airway pathogens. An additional goal was to characterize the lower respiratory flora of these patients. Predictive values were defined as the proportion of oropharyngeal culture results that accurately reflected the results of bronchial cultures. Predictive values of positive oropharyngeal cultures in nonexpectorating patients were 83% (95% confidence interval 36 to 100%) for Pseudomonas aeruginosa and 91% (59 to 100%) for Staphylococcus aureus. Predictive values of negative oropharyngeal cultures were lower: 70% (48 to 86%) for R aeruginosa and 80% (52 to 96%) for S. aureus. A relatively high proportion of nonexpectorating CF patients less than 10 yr old had R aerusginosa (11 of 24, 46%) or Klebsiella species (5 of 24, 21%) in their lower airways. The isolation of Klebsiella was associated with younger age (p = 0.03) and recent administration of antistaphylococcal antibiotics (p = 0.05). Our results suggest that oropharyngeal cultures yielding R aeruginosa or S. aureus are highly predictive, but such cultures lacking these organisms do not rule out the presence of these pathogens in the lower airways of CF patients. PMID- 1859057 TI - Repeatability of histamine bronchial challenge and comparability with methacholine bronchial challenge in a population of Australian schoolchildren. AB - To measure the repeatability of the bronchial challenge test and the comparability of histamine and methacholine as provoking agents, we studied a population sample of children and conducted histamine bronchial challenge tests on each of 3 consecutive days followed by a methacholine bronchial challenge on the fourth day. Bronchial responsiveness was measured using the rapid inhalation method. A total of 393 children had satisfactory bronchial challenge data for all 4 days. The measurements derived from the dose-response curve were the PD20 FEV1, which was measured as the provoking dose causing a 20% fall in FEV1, and the dose response slope (DRS), which was measured as the percentage fall in FEV1 at final dose/total dose administered. Children who had a PD20 FEV1 were categorized as having bronchial hyperresponsiveness (BHR). The percentage of children with BHR each day was between 7 and 11. One-third of the children with BHR reacted only to histamine or methacholine. The within-subject range for histamine PD20 FEV1 values compared with methacholine suggested that histamine and methacholine are not directly comparable bronchial challenge agents. The dose-response slope values, which could be obtained for all children, had slightly better repeatability than PD20 FEV1 values. Because DRS values obtain data for the entire sample, have good repeatability, and are equally repeatable in children with normal responsiveness or bronchial hyperresponsiveness, they should prove more useful than PD20 FEV1 values for measuring bronchial responsiveness in populations. PMID- 1859058 TI - Assessment of airway responsiveness in infants with cystic fibrosis. AB - We compared the responses of cystic fibrosis (CF) (N = 14) and normal (N = 14) infants with inhaled methacholine. Airway function was assessed by forced expiratory flows at functional residual capacity (Vmax FRC) generated by the rapid compression technique, and methacholine responsiveness was quantitated as (1) TC: the threshold concentration to decrease Vmax FRC by 2 SD from baseline; (2) PC50: the provocative concentration to decrease Vmax FRC by 30%; and (3) SPC30; the slope of the dose-response curve between TC and PC30. There were no significant differences in age between CF and normal infants (16 +/- 8 versus 17 +/- 5 months, p greater than 0.3); however, the CF infants were shorter (74 +/- 10 versus 81 +/- 5 cm, p less than 0.05), had lower absolute Vmax FRC (241 +/- 103 versus 374 +/- 113 ml/s, p less than 0.001), and tended to have lower percentage of predicted flow values (87 +/- 13 versus 111 +/- 34%, p less than 0.10). Comparison of the indices of airway responsiveness revealed no difference in logTC; however, the CF infants had smaller, more negative values for logPC30 ( 0.76 +/- 0.52 versus -0.22 +/- 0.53, p less than 0.02) and steeper slopes to their dose-response curves (logSPC30, 2.42 +/- 0.45 versus 1.88 +/- 0.74, p less than 0.025). Indices of airway responsiveness correlated significantly with baseline Vmax FRC (% of predicted). After the influence of baseline flow upon airway responsiveness was accounted for by multiple linear regression analysis, there was a tendency for CF infants to be more responsive than control infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859059 TI - Short-term effect of albuterol, delivered via a new auxiliary device, in wheezy infants. AB - In a double-blind, placebo-controlled study, the response of lung function to albuterol, topically administered by a metered-dose inhaler (MD) through a baby adapted auxiliary device, was evaluated in 36 wheezy infants (1.6 to 25.2 months of age; median 8.1 months). The auxiliary device contains an air chamber of 350 ml and two low-resistant valves separating the inspiratory from the expiratory line. After baseline lung function measurements by infant whole-body plethysmography, the patients were randomly assigned to inhale either three times two puffs albuterol (100 micrograms/puff) or three times two puffs placebo at 5 min intervals. Changes in the degree of pulmonary hyperinflation, estimated by thoracic gas volume (TGV) and/or in the degree of bronchial obstruction, estimated by thoracic gas volume (TGV) and/or in the degree of bronchial obstruction, estimated by airway conductance (Gaw), were measured at 5-min intervals for up to 30 min. TGV and Gaw were expressed as standard deviation scores (SDS) of values predicted, and patients improving TGV and/or Gaw more than 2 SD were considered responders. In comparison with placebo, a significant percentage improvement in TGV (by the mean 26 to 53%) and a significant percentage improvement in Gaw (by the mean 34 to 51%) could be found in the active treatment groups. The study documents the usefulness of a new auxiliary device for the administration of aerosolized bronchodilators to wheezy infants. PMID- 1859060 TI - Dissimilarity in methacholine and adenosine 5'-monophosphate responsiveness 3 and 24 h after allergen challenge. AB - Bronchial hyperresponsiveness (BHR) to methacholine and adenosine 5' monophosphate (AMP) was studied in 15 allergic asthmatic patients before and 3 and 24 h after allergen challenge with house dust mite (HDM). Subjects attended the clinic on 3 consecutive days. On the first day a control solution was inhaled, and methacholine or AMP challenge was performed 3 h later. The next day HDM was inhaled, and 3 and 24 h later methacholine or AMP challenge was performed again. There were no significant difference in FEV1 baseline value between any of the study days. PD20 HDM, percentage decrease in FEV1, and AUC for both the EAR and LAR were not significantly different in the methacholine and AMP studies. After HDM challenge, PC20 methacholine decreased significantly from a geometric mean (+/- SEM) starting value of 1.39 +/- 0.63 mg/ml to 0.30 +/- 0.78 mg/ml (p less than 0.001) at 3 h and to 0.22 +/- 0.75 mg/ml (p less than 0.001) at 24 h. The magnitude of the decrease in PC20 methacholine at 3 h correlated with the severity of the late asthmatic reaction (LAR) as measured by the percentage fall in FEV1 and area under the curve (AUC) (r = -0.60 and r = 0.55; p less than 0.05). A significant decrease was observed in the PC20 AMP at 3 h, from a geometric mean value of 12.2 +/- 0.96 mg/ml after challenge with the control solution to 4.47 +/- 0.99 mg/ml (p less than 0.05) after HDM challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859061 TI - Transient airway cooling modulates dry-air-induced and hypertonic aerosol-induced bronchoconstriction. AB - Airflow-induced bronchoconstriction (AIB) may be initiated in asthmatic patients by inhaling dry air during eucapnic hyperventilation or exercise. Hypertonic aerosol-induced bronchoconstriction (HIB) also occurs in these patients, but it differs from AIB by exhibiting a faster time course. Although AIB and HIB probably increase airway fluid osmolality, only AIB is associated with airway cooling. In light of the similarities between our canine model and human AIB, we examined peripheral airway responses to dry air and hypertonic aerosol challenge. Specifically, we studied the magnitude and time course of these responses in an in situ, isolated, perfused lobe in which airway temperature was independently controlled. At body temperature, HIB peaked immediately after challenge, whereas transient airway cooling during aerosol challenge delayed HIB. In contrast, airway cooling attenuated AIB but did not alter its time course. Hypocapnia- and histamine-induced responses were not affected by airway cooling, suggesting that smooth muscle function was not impaired. To the extent that the mechanisms producing AIB in dogs and in humans are similar, our results suggest that (1) changes in airway fluid osmolality initiate AIB, (2) AIB = HIB + Cooling, and (3) exercise-induced asthma results from an imbalance between an excitatory pathway stimulated by airway drying and an inhibitory pathway initiated by airway cooling. PMID- 1859062 TI - Epithelial modulation of airway smooth muscle response to endothelin-1. AB - We investigated the role of epithelial modulation of contraction caused by endothelin-1 in airway smooth muscle in guinea pigs in situ. Airway responses were assessed isometrically as tracheal force and simultaneously as change in lung resistance. Intravenous administration of 10(-8) mol/kg endothelin-1 caused a biphasic response in tracheal active tension: initial relaxation (-0.82 +/- 0.22 g/cm after 30 s, p less than 0.05 versus baseline) followed by contraction (1.65 +/- 0.28 g/cm after 7 min, p less than 0.05 versus baseline). Endothelin-1 also elicited immediate bronchoconstriction; lung resistance increased from 0.148 +/- 0.030 to 0.992 +/- 0.274 cm H2O/L/s (p less than 0.005) after 10(-8) mol/kg endothelin-1 given intravenously. Active tension elicited by 10(-8) mol/kg endothelin-1 after removal of the epithelium from the tracheal segment (0.59 +/- 0.16 g/cm) was less than in segments with an intact epithelium (1.65 +/- 0.28 g/cm, p less than 0.01). Both tracheal contraction and bronchoconstriction were attenuated by pretreatment with indomethacin orally, BW 755C intravenously, or substitution of endothelin-C-terminal hexapeptide for endothelin-1. However, the initial tracheal relaxation response was similar after each intervention. These data suggest actions of endothelin-1 that have not been demonstrated previously: (1) endothelin-1 elicits a biphasic response in tracheal smooth muscle (an initial relaxation response elicited by the carboxy-terminal residues and a later contractile response that requires synthesis of a cyclooxygenase mediator) and (2) epithelium adjacent to the airway smooth muscle modulates contraction elicited by endothelin-1. PMID- 1859064 TI - Flow resistance in patients with chronic obstructive pulmonary disease in acute respiratory failure. Effects of flow and volume. AB - The flow and volume dependence of the total resistance of the respiratory system (Rrs) was investigated in six mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) using a simple, rapid method. Isovolume Rrs flow (V) relationships obtained at different inflation volumes (range 0.1 to 1 L) fitted (p less than 0.001) the following function: Rrs = a/V + b + cV, where a, b, and c are constants. The term "a/V" in this equation represents the hyperbolic decrease in thoracic tissue resistance with increasing flow; the term "cV" represents the linear increase in airway resistance with increasing flow. Rrs initially decreased with increasing V because at low flow the weight of the a/V was greater than that of the cV. At higher flow, however, cV became predominant and hence Rrs tended to increase. At an inflation volume of 0.5 L, minimum Rrs occurred at average inflation flow of 1.28 L/s. At low flow, Rrs increased progressively with increasing inflation volume; at inflation V greater than 1 L/s, the highest values of Rrs were obtained at low inflation volumes. The flow and volume dependence of Rrs implies that, for comparative purposes, measurements of Rrs should be standardized to a fixed inflation flow and volume. PMID- 1859063 TI - Late-phase asthmatic reaction to inhaled allergen is associated with early recruitment of eosinophils in the airways. AB - To determine whether a link exists between the recruitment of inflammatory cells in the airways and the development of the late-phase asthmatic reaction, we studied with bronchoalveolar lavage 54 asthmatic patients either at baseline (10 patients) or 4 h (11 patients), 24 h (13 patients), and 72 h (20 patients) after allergen inhalation challenge. Among the patients studied 4 h after allergen challenge, five were known to have a late-phase asthmatic response and showed a significant increase in the number and percentage of eosinophils in bronchoalveolar lavage compared with either patients without late-phase response (p less than 0.05) or unchallenged patients (p less than 0.01). Both the number and the percentage of eosinophils in bronchoalveolar lavage were also increased (p less than 0.05) in patients without a late-phase asthmatic reaction studied 24 h but not in those studied 4 h after allergen challenge. The numbers and the percentages of macrophages, neutrophils, or lymphocytes did not differ significantly among the different groups of patients. Of the patients studied 4 and 24 h after allergen challenge, only those with a late-phase asthmatic response showed an increased airway responsiveness to methacholine 1 h before bronchoalveolar lavage. We conclude that the development of the late-phase asthmatic response to allergen inhalation challenge and the allergen-induced increase in airway responsiveness are associated with an early recruitment of eosinophils in the airways. PMID- 1859065 TI - Sustained improvement in gas exchange after negative pressure ventilation for 8 hours per day on 2 successive days in chronic airflow limitation. AB - Negative pressure ventilation (NPV) was applied for 6 to 8 h/day for 2 consecutive days in 13 patients with severe airflow limitation and chronic respiratory failure. After cessation of NPV, the mean arterial blood gases were improved in 10 patients, and this improvement was sustained for the nex 2 days in eight patients, for 3 days in seven patients, and was still present in four patients on the fourth day. Respiratory muscle strength improved in all patients, but there was no relationship between the increase in strength and sustained improvement in gas exchange. Ventilation and respiratory pattern were unchanged in all patients, but the mean VD/VT fell and VA rose while the VO2 and VCO2 fell. The ventilatory responses to hypoxia and hypercapnia increased in patients who demonstrated sustained improvement in blood gases. The mechanism underlying the sustained improvement in gas exchange following NPV is not clear but is likely multifactorial. PMID- 1859066 TI - Constant-flow insufflation prevents arterial oxygen desaturation during endotracheal suctioning. AB - In mechanically ventilated patients, disconnection from the ventilator and endotracheal suctioning can induce major arterial oxygen desaturation resulting from apnea, changes in inspired oxygen fraction, and decrease in lung volume. The aim of this study was to test the efficacy of a simple method of delivering oxygen and maintaining lung volume during this process. Our study was conducted in two parts. In the first part, constant-flow insufflation of oxygen (CFI) was used in seven patients ventilated for acute respiratory failure (PaO2/FlO2 = 347 +/- 33 mm Hg) as a means of maintaining arterial oxygenation during apnea and disconnection from the ventilator. CFI was administered via a modified endotracheal tube in which small capillaries allowed delivery of a high-velocity jet flow near the tracheal end of the tube during disconnection from the ventilator. In comparison to apnea alone, CFI prevented a fall in arterial oxygen tension (16 +/- 7 mm Hg during CFI versus 117 +/- 27 during apnea, after 90 s of disconnection in the two situations, p less than 0.001), whereas it did not reduce the development of hypercapnia. The efficacy of CFI resulted both from the injection of oxygen into the trachea and from the maintenance of positive alveolar pressure induced by air entrainment (mean 10.4 +/- 1.1 cm H2O), preventing a fall in lung volume usually occurring after disconnection (+338 +/- 88 ml during CFI versus -344 +/- 64 ml during apnea, p less than 0.01). In the second part of the study CFI was used to prevent arterial oxygen desaturation induced by endotracheal suctioning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859067 TI - Evolution of nocturnal oxyhemoglobin desaturation in patients with chronic obstructive pulmonary disease and a daytime PaO2 above 60 mm Hg. AB - We studied 31 clinically stable chronic obstructive pulmonary disease (COPD) patients with a PaO2 greater than or equal to 60 mm Hg using polysomnographic sleep study at baseline (between 1983 and 1986) and at a mean follow-up time of 42.5 months to examine the evolution of rapid-eye-movement (REM) sleep nocturnal oxyhemoglobin desaturation (NOD). Arterial blood gases and spirometry measured at baseline and follow-up were compared with mean nocturnal SaO2 and to other REM sleep SaO2 parameters. We postulated that the onset of NOD would be seen most frequently in those patients with marked derangements of lung mechanics and greater longitudinal deterioration in arterial blood gases. Eight of the subjects developed REM-NOD on follow-up polysomnography. The appearance of REM-NOD was not related, or only minimally so, to initial PaO2, PaCO2, or mean nocturnal SaO2. Upon follow-up, however, the onset of NOD was always associated with deterioration of daytime PaO2 and PaCO2, mainly in those patients with the most severe baseline derangement of spirometry (lung mechanics). On the other hand, one group showed equivalent deterioration in daytime PaO2 and a stable PaCO2 but had less severely deranged baseline mechanics and demonstrated a fall in mean nocturnal SaO2 only. The findings in this latter group indicate that the development of NOD is not purely a result of decreasing daytime PaO2. We conclude that the onset of REM-NOD is mainly related to a severe derangement of lung mechanics with deterioration of resting awake gas exchange (progressive hypoxemia, hypercarbia, and worsening airflow).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859068 TI - Effect of hypercapnia on total pulmonary resistance during wakefulness and during NREM sleep. AB - We investigated the effect of different levels of hypercapnia on total pulmonary resistance (RL) in 13 subjects ranging from nonsnorers with low RL to snorers with high RL and dynamic narrowing of the upper airway during inspiration. Added CO2 was adjusted to achieve a steady-state increase in PETCO2 of +2, +4, or +6 mm Hg. RL was measured at peak inspiratory flow (RLpf), at maximal resistance within breath (RLmax), and at 10 equally spaced points within inspiration in several trials. During wakefulness, hypercapnia was associated with decreased RLmax. During steady state +6 mm Hg hypercapnia, RLmax decreased by 30% (p less than 0.01). During NREM sleep, low levels of hypercapnia did not affect RL. However, +6 mm Hg hypercapnia was associated with decreased RLmax in six of eight subjects (p = 0.07), especially in subjects with high RLmax during room air breathing. The effects of hypercapnia on RLpf paralleled its effect on RLmax. We concluded that (1) the decrease in RL during awake hypercapnia suggests an increase in upper airway dimensions and stiffness, (2) the absence of increased RL during low level NREM hypercapnia (despite the increase in inspiratory flows and collapsing pressures) also suggests an increase in upper airway dimensions and stiffness, and (3) upper airway dilating muscles appear to be recruited in a coordinated fashion with inspiratory muscles in normal humans during NREM sleep. The implications of these findings in patients with obstructive sleep apnea are not clear at this point. PMID- 1859069 TI - Diaphragmatic energetics during prolonged exhaustive exercise. AB - The present study was carried out to examine diaphragmatic O2 extraction and lactate and ammonia production during prolonged exhaustive exercise. Experiments were performed on nine healthy exercise-conditioned ponies in which catheters had been implanted in the phrenic vein previously. Blood-gas variables and lactate and ammonia concentrations were determined on simultaneously obtained arterial and phrenic-venous blood samples at rest and during 30 min of exertion at 15 mph + 7% grade (heart rate, 200 beats/min; approximately 90% of maximum). Arterial O2 tension and saturation were maintained near resting value but CO2 tension decreased markedly with exercise, and because of increased hemoglobin concentration, arterial O2 content rose. Concomitantly, phrenic venous O2 tension, saturation and content decreased markedly (23.6 +/- 1 mm Hg, 24.5 +/- 2%, 5.2 +/- 0.3 ml/dl at 3 min of exertion) and significant fluctuations did not occur as exercise duration progressed to 30 min. Diaphragmatic arteriovenous O2 content difference and O2 extraction rose from 4 +/- 0.3 to 16 +/- 0.5 ml/dl and from 30 +/- 3 to 75 +/- 1% at 3 min of exercise, and significant deviations did not occur as exercise duration progressed. Arterial lactate and ammonia levels increased during exercise, indicating their release from working limb muscles. Phrenic-venous values of lactate and ammonia did not exceed arterial values. Ponies sweated profusely and were unable to keep up with the belt speed in the last 4 to 5 min of exercise. Constancy of phrenic arteriovenous O2 content difference in exercise indicated ability to adjust perfusion in diaphragm so as to adequately meet its O2 needs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859070 TI - Oral mucosal stimulation modulates intensity of breathlessness induced in normal subjects. AB - Patients with chronic obstructive pulmonary disease (COPD) often report an increase in breathlessness when they breathe through a mouthpiece. We hypothesized that stimulation of receptors in the oral mucosa modulates the sensation of breathlessness. We studied 10 normal naive volunteers in whom breathlessness was induced by having them breathe for 4 min with an inspiratory resistive load (18 cm H2O/L/s) while breathing was stimulated by CO2 inhalation (end-tidal PCO2 maintained at 55 mm Hg). Initially, subjects breathed with a tight-fitting face mask and inspiratory flow was displayed on a storage oscilloscope. In subsequent trials, the subjects were asked to match this trace, which controlled ventilation and the pattern of breathing. Subjects performed eight trials, four with the tight-fitting mask only (M) and four with a mouthpiece and the mask (MM). M and MM were alternated; the initial condition was chosen at random. Following each of the trials, subjects rated the intensity of their breathlessness by choosing a number from a modified Borg scale. On the average, subjects were more breathless while breathing with the mask and mouthpiece than with the mask alone (mean ratings of breathlessness 6.6 +/- 1.1 and 5.6 +/- 1.8 units, p less than 0.01). Six subjects repeated the protocol on 2 additional days: 1 day with inhalation of warm (34 degrees C), humidified air and 1 day after topical application of 4% lidocaine to the oral mucosa. Both these interventions abolished the differences in breathlessness between mask and mouthpiece and mask alone. We conclude that afferent information from oral mucosal stimulation influences the intensity of breathlessness. PMID- 1859071 TI - Structural changes in the airways of sensitized brown Norway rats after antigen challenge. AB - The purpose of this study was to quantitate the structural changes in the airways of sensitized rats after repeated challenge with aerosolized antigen and to examine the relationship between these changes and alterations in responsiveness to methacholine (MCh). We studied 28 Brown Norway rats that were actively sensitized to ovalbumin (OA). Responsiveness to aerosolized MCh was quantitated as the concentration of MCh required to double pulmonary resistance (EC200 RL). The EC200 RL was determined before and 1 and 5 days after three inhalational challenges with OA (n = 17) or saline (n = 11) at 5-day intervals (on Days 14, 19, and 24 after sensitization). Responsiveness to MCh increased after OA; EC200 RL fell from 1.71 to 0.71 mg/ml at 1 day (p less than 0.01) and 0.87 mg/ml at 5 days (p less than 0.02) after OA but did not change after saline challenge. Formalin-fixed lungs from a sample of OA-challenged (n = 12) and saline challenged (n = 6) animals were paraffin embedded, and 5-microns sections were stained with hematoxylin-phloxin-saffron. Cross-sectional areas of the airway wall and smooth muscle (ASM) were determined for all intrapulmonary membranous airways. There was an approximately twofold increase in the quantity of airway smooth muscle in airways of OA-challenged animals compared with saline-challenged control animals. Airway wall area did not change significantly. There was a correlation (r = 0.618, p less than 0.05) between the quantity of ASM in large airways (basement membrane length 2.00 to 2.99 mm) and change in responsiveness to MCh. PMID- 1859072 TI - Three-dimensional upper airway computed tomography in obstructive sleep apnea. A prospective study in patients treated by uvulopalatopharyngoplasty. AB - The success of uvulopalatopharyngoplasty in treating obstructive sleep apnea varies considerably. Some of this variability may be accounted for by differences in the site of upper airway narrowing. To determine whether preoperative awake upper airway and soft tissue volumes predict the response to uvulopalatopharyngoplasty, preoperative awake computed tomograms (CT) of the upper airway were performed on 60 consecutive patients with symptomatic obstructive sleep apnea. Tracings were made from the CT scans of upper airway, tongue, and soft palate. Computer software was used to determine the cross sectional area and volume of the upper airway, tongue, and soft palate. Patients underwent overnight polysomnograms before and 3 months after uvulopalatopharyngoplasty. Tongue volume was larger (p less than 0.02) and both upper airway to tongue volume (p less than 0.0005) and oropharynx to soft palate volume ratios (p less than 0.01) were smaller in obese patients. A good response to uvulopalatopharyngoplasty as defined by a postoperative apnea index of less than 5 apneas/h or a reduction in apnea index greater than or equal to 50% was seen in 50 patients (83%). Patients who had a good response had a smaller oropharyngeal cross-sectional area (p less than 0.01), a smaller upper airway volume (p less than 0.05), a smaller upper airway to tongue volume ratio (p less than 0.01), and a smaller oropharynx to soft palate volume ratio (p less than 0.05). Obese patients with obstructive sleep apnea have larger tongues and smaller upper airways relative to tongue and soft palate size. Patients with smaller upper airways, particularly relative to tongue and soft palate size, have a good response to uvulopalatopharyngoplasty. PMID- 1859073 TI - Pulmonary considerations of organ transplantation. Part 3. PMID- 1859074 TI - Matrix-driven pneumocyte differentiation. AB - This commentary presents evidence in support of a hypothesis that adult mammalian alveolar epithelial basement membrane possesses functional and structural domains that determine sites at which type I and type II cells localize. The hypothesis provides a framework for understanding how, after normal repair of the epithelium, a constant ratio of type I and type II cells, and the localization of the cell types is maintained. PMID- 1859075 TI - T lymphocyte activation in patients with active tuberculosis. AB - Soluble interleukin-2 receptor (sIL-2R) is a marker of T lymphocyte activation. We measured the amount of serum sIL-2R in 35 patients with active tuberculosis before the initiation of antituberculous treatment. Twenty had pulmonary parenchymal lesion, 8 had tuberculous pleural effusion, and 7 had tuberculous lymphadenitis. The serum sIL-2R values were markedly elevated in patients with pulmonary tuberculosis (parenchymal lesion and pleural effusion) compared with patients with tuberculous lymphadenitis (2,612 +/- 536 versus 538 +/- 121 U/ml, p = 0.023), old, inactive tuberculosis (335 +/- 23 U/ml, p = 0.001), and normal control subjects (376 +/- 38 U/ml, p = 0.001). No significant difference was found between patients with parenchymal lesion and those with tuberculous pleural effusion. There was a positive correlation between serum sIL-2R values and the extent of disease on chest radiograph (r = 0.58, p less than 0.001). We conclude that the amount of sIL-2R may be a useful marker of disease activity and extent of involvement in patients with active tuberculous lesions. PMID- 1859076 TI - Obstructive sleep apnea during pregnancy. Therapy and implications for fetal health. AB - A 32 yr-old woman in her last trimester of pregnancy was found to have severe obstructive sleep apnea (OSA). The overnight polysomnogram demonstrated an apnea plus hypopnea index of 159 events per hour. Apneas were associated with severe oxygen desaturation to 40% during rapid eye movement sleep, maternal bradycardia, and second degree heart block. External cardiotocography showed normal fetal heart rate reactivity to fetal movements, even during the apneas and episodes of oxygen desaturation. Nasal continuous positive airway pressure at a level of 15 cm H2O effectively treated the apneas and desaturation and had no effect on the fetal heart rate. The patient was induced electively during the 39th wk of pregnancy and gave birth to a newborn with growth retardation. Early recognition and treatment of OSA in pregnancy might prevent problems with fetal development. PMID- 1859077 TI - Health effects of atmospheric acids and their precursors. Report of the ATS workshop on the Health Effects of Atmospheric Acids and their Precursors. PMID- 1859078 TI - Intact epithelial barrier function is critical for resolution of alveolar edema in humans. PMID- 1859079 TI - Surfactant replacement improves lung recoil in rabbit lungs after acid aspiration. PMID- 1859080 TI - An outbreak of suppurative lymphadenitis connected with BCG vaccination in Austria, 1990/1991. PMID- 1859081 TI - Fatal mistaken identity. PMID- 1859082 TI - Human longevity and aging: possible role of reactive oxygen species. AB - A brief overview has been given of the biological nature of human aging processes, where it has been emphasized that, in addition to the diseases of aging, there is also great economic loss as a result of human aging processes that began many years before medical costs related to aging begin to escalate. Because of the ubiquitous nature of aging, reducing the function of essentially all physiological processes, it appears that the only long-term solution to human aging problems is to decrease uniformly the aging rate of the entire body. Although the uniform decrease of aging rate has usually been considered impossible, where emphasis has consequently been placed on diseases of aging by the medically-orientated investigator, there is now at least one theoretical argument, accompanied by some experimental data, that suggests that progress can be made in achieving this goal. This progress has been based on the longevity determinant gene hypothesis predicting the existence of a relatively few key regulatory factors governing aging rate of the entire organism. If this hypothesis is not true, then indeed the prospect for significant intervention into human aging would appear impossible in the near future. Experiments have been briefly reviewed testing the longevity determinant gene hypothesis, the possibility that aging may be a result of dysdifferentiation and if aging rate is determined by mechanisms acting to stabilize the differentiated state of cells. In testing the dysdifferentiation hypothesis of aging, there is not yet much data one way or the other. It is evident, however, that changes in gene expression do occur with age, sometimes involving endogenous retroviruses or oncogenes. Other morphological evidence shows an increase with age in unusual cell type such as metaplasia cells. However, there is considerably more evidence indicating that aging may be a result of genetic instability (as it is in cancer) and that longer lived species appear to have a more stable genetic apparatus and superior protective mechanisms against reactive oxygen species. There is a striking similarity in this model of aging and models of cancer, and much might be gained in bringing together these two fields of research. Taking all of these data together, as summarized in Table 14, it appears we may be on the right track and that mechanisms acting to protect DNA against oxidative damage may be one class of longevity determinant mechanisms. There is of course much work remaining to be done, some of which is listed in Table 15 in terms of our knowledge and our gaps of knowledge in this field. PMID- 1859083 TI - Behavioral and electrocortical spectrum power effects after microinfusion of lymphokines in several areas of the rat brain. PMID- 1859084 TI - Enkephalin-induced stimulation of humoral and cellular immune reactions in aged rats. AB - Twenty-month-old Wistar rats received intraperitoneal injections of the opioid pentapeptide, methionine-enkephalin (Met-Enk) in periods before and after immunization with cellular and soluble antigens. Animals were treated with 0.2 mg of Met-Enk/kg b.w., a dose previously found to increase immune capacity in young adult rats. Saline-treated 20-month-old, and Met-Enk-treated rats and saline treated 8-week-old controls were set up for each experimental group. Immune performance was evaluated by plaque-forming cell response, antibody production and various immunoinflammatory reactions. At autopsy, thymus and spleen were weighed and processed for histological examination. The results showed that 0.2 mg dose of Met-Enk produced significant enhancement of both humoral and cellular immune responses in senescent rats. Methionine-enkephalin treatment also induced a significant increase in thymus and spleen weights in these animals. Analysis of the cellular make up of these organs revealed the enlargement of cortical and medullary areas, and pronounced pyroninophilia in the subcortical zone of the thymus and thymus-dependent areas of the spleen. The results suggest that Met-Enk exerts an immunorestorative activity in aged animals, and that changes in the opioid system may play an important role in the maintenance of immune functions during senescence. PMID- 1859085 TI - Immunostimulatory activity of prothymosin-alpha in senescence. AB - In this study we evaluated the immunorestorative activity of prothymosin-alpha (ProT-alpha) in senescence. Aged rats were repeatedly injected with ProT-alpha after antigen challenge. Both humoral and cell-mediated immune reactions were tested. The results show that ProT-alpha exerted a marked immunopotentiating effect in aged rats. Moreover, ProT-alpha induced enhancement of PFC response, and skin hypersensitivity reactions were more pronounced in senescent rats than in young adult controls. ProT-alpha treatment increased thymus and spleen weights in aged rats, and induced qualitative and quantitative improvements of the cellular make-up of the thymus and thymus-dependent areas of the spleen. The results imply that "restoring" thymus endocrine function by exogenous administration of ProT-alpha may improve immune system homeostasis in senescence. PMID- 1859086 TI - Band 3 in aging and neurological disease. AB - Senescent cell antigen appears on old cells and marks them for death by initiating the binding of IgG autoantibody and subsequent removal by phagocytes in mammals and other vertebrates. We have created a synthetic aging antigen that blocks binding of IgG to senescent cells in vitro. Synthetic senescent cell antigen might be effective in preventing cellular destruction in vivo in certain diseases, and can be used to manipulate cellular life span in situ. Senescent cell antigen is generated by the modification of an important structural and transport membrane molecule, protein band 3. Band 3 is present in cellular, nuclear, Golgi, and mitochondrial membranes as well as in cell membranes. Band 3 proteins in nucleated cells participate in cell surface patching and capping. Band 3 maintains acid-base balance by mediating the exchange of anions (e.g., chloride, bicarbonate), and is the binding site for glycolytic enzymes. It is responsible for CO2 exchange in all tissues and organs. Thus, it is the most heavily used anion transport system in the body. Band 3 is a major transmembrane structural protein which attaches the plasma membrane to the internal cell cytoskeleton by binding to band 2.1 (ankyrin). Oxidation generates senescent cell antigen in situ. Band 3 is present in the central nervous system, and differences have been described in band 3 between young and aging brain tissue. One autosomal recessive neurological disease, choreoacanthocytosis, is associated with band 3 abnormalities. The 150 residues of the carboxyl terminus segment of band 3 appear to be altered. In brains from Alzheimer's disease patients, antibodies to aged band 3 label the amyloid core of classical plaques and the microglial cells located in the middle of the plaque in tissue sections, and an abnormal band 3 in immunoblots. Band 3 protein(s) in mammalian brain performs the same functions as that of erythroid band 3. These functions is anion transport, ankyrin binding, and generation of senescent cell antigen, an aging antigen that terminates the life of cells. Structural similarity of brain and erythroid band 3 is suggested by the reaction of antibodies to synthetic peptides of erythroid band 3 with brain band 3, the inhibition of anion transport by the same inhibitors, and an equal degree of inhibition of brain and erythrocyte anion transport by synthetic peptides of erythroid band 3. One of these segments, pep-COOH, contains antigenic determinants of senescent cell antigen.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1859087 TI - Platelet autoantibodies in dementia and schizophrenia. Possible implication for mental disorders. AB - Platelets isolated from blood of demented and schizophrenic patients were found to bear surface antibodies at a considerably higher titer than those found on platelets from normal age-matched groups or patients with affective disorders. The platelet count in demented and schizophrenic patients correlated inversely with the level of the platelet associated antibodies (PAA) which suggested an autoimmune route of opsonization. In most individual cases of dementia or schizophrenia PAA and platelet count were found to oscillate with time between high PAA-low platelet number and low PAA-high platelet number in approximately inverse correlation. PAA isolated from demented patients were found to cross react with platelets from normals and with brain tissue from rats. Furthermore, molecular weights of specific brain antigens were identified by binding to PAA. These observations support the possibility that PAA might be implicated in the etiology of some mental dysfunctions associated with dementia and schizophrenia. PMID- 1859088 TI - Calcitonin gene-related peptide in the developing and aging thymus. An immunocytochemical study. AB - Calcitonin gene-related peptide (CGRP) is known to block Con A and PHA induced T cell proliferation. As a first step in determining the role of this peptide in T cell education and function we have studied the distribution of CGRP within the developing mouse thymus using immunocytochemistry. CGRP-like immunoreactivity (CGRP-IR) was found in the thymic nerves in close proximity to blood vessels in the 17-day-old embryonic mouse thymus. A discrete population of small cells at the cortico-medullary junction also stained intensely for CGRP. As the mouse thymus reached maturity (three to eight weeks) CGRP innervation became more dense, with fibers running along the vasculature at the cortico-medullary boundary, then branching into the cortical and medullary regions. Some fibers were invested in the blood vessels while a large portion formed varicosities among the cells of the thymus. In the mature thymus, the small CGRP-IR cortico medullary cells were more numerous, and CGRP-IR was also found in subcapsular and trabecular mast cells. The pattern of innervation remained the same in the aging mouse thymus (six months), but there appeared to be somewhat fewer cortico medullary cells and an increase in mast cell number. In the aged (eighteen months) thymus, the small CGRP-IR cortico-medullary cells were rarely seen, but mast cells were more numerous, most of which stained positively for CGRP, in the connective tissue. Nerves containing CGRP-IR generally had the same distribution as in the younger mice but appeared somewhat truncated. The distribution of CGRP IR nerves in the mouse thymus at different stages of development was similar to that reported for cholinergic (AChE-positive) nerves. Since the brain-stem vagal nuclei have been shown by retrograde transport studies to project to the thymus as well as to contain CGRP-IR neurons, our findings suggest that CGRP-IR thymic nerves may be derived from the vagus complex. PMID- 1859089 TI - Survey of thymic hormone effects on physical and immunological parameters in C57BL/6NNia mice of different ages. AB - Immunosenescence occurs with aging, which is seen in decline in response to mitogens PHA, ConA, decline in cell-mediated immunity, increase in anemia, and increase in autoimmune antibodies to erythrocytes and DNA. These studies compared FTS, TP5, TM4, and TF5 in C57BL/6NNia mice. Mice aged 4, 26, 52, 78 and 104 wk were treated with various hormones 5x/wk for 3 wk and monitored for hormonal effects on weight; hematocrit; peripheral blood, spleen, and thymic cell numbers; spleen and peripheral blood cell mitogen responses to PHA, ConA, LPS; IgM hemolysin autoantibody; and cell-mediated cytotoxicity to P815 allogenic cells. Hormone treatments altered mitogen responses, enhanced IgM hemolysin autoantibody production, and modulated cell-mediated immune responses. The effects were not consistent for every hormone. There was a tendency for enhancement in younger mice and suppression in older animals. Treatment with FTS showed the greatest changes in either enhancing or suppressing the different parameters measured. The hormonal effects appeared to be age specific in that certain activities were altered for certain age groups but not in others. Hormone treatment did not restore any immune parameters in old mice to the level of young animals. In general, the different hormones did not consistently produce the same effects in C57BL/6NNia mice of different age groups. Even though all animals received from National Institutes on Aging (NIA) animal models program were held under strictly controlled conditions, intrinsic variations between cohorts of different ages are difficult to control. Cohorts of aging animals tested at different times might be intrinsically different. This inherent variability in the cohorts could affect the range of activity, specificity and reproducibility of hormone effects in vivo. Most importantly, it should be emphasized that cross-sectional data identifies age differences rather than age changes. There is no assurance that age changes in any individual or in all subpopulations follow this pattern. In our studies only healthy animals were used. Old, sick, or tumor-bearing animals were culled out prior to being sent to us. Therefore, the 78- and 104-wk-old mice represent selected healthy cohorts. The age changes that take place can be answered only from repeated measurements made in the same individual over time. PMID- 1859090 TI - Pituitary-adrenocortical and pineal activities in the aged rat. Effects of long term treatment with acetyl-L-carnitine. PMID- 1859091 TI - Phospholipase A2 as a "death trigger" in the aging process. The use of PLA2 inhibitors as antiaging substances. PMID- 1859092 TI - The decline of the immune response during aging: the role of an altered lipid metabolism. PMID- 1859093 TI - The pineal control of aging. The effects of melatonin and pineal grafting on the survival of older mice. PMID- 1859094 TI - The role of zinc in neuroendocrine-immune interactions during aging. PMID- 1859095 TI - Retardation of the aging processes in rats by food restriction. PMID- 1859096 TI - Longevity-assurance mechanisms and caloric restriction. PMID- 1859097 TI - Effects of factors prolonging life span on carcinogenesis. PMID- 1859098 TI - Pathogenetic approaches to prevention of age-associated increase of cancer incidence. PMID- 1859099 TI - Age changes in chromatin: accumulative or programmed? PMID- 1859100 TI - Genetic and environmental modulations of chromosomal stability: their roles in aging and oncogenesis. AB - The primary objective of this review is to suggest a major role of cytogenetic pathology in the genesis of both the neoplastic phenotype and the senescent phenotype of aging mammalian organisms. It is hypothesized that allelic variation at a number of genetic loci that have the potential to modulate various types of chromosomal mutation could account, in part, for species-specific variations in maximum life-span potentials and the times of onset of characteristic age-related neoplasms. As a corollary to this proposition, attention is directed to the potential importance of environmental clastogens and aneugens as both oncogenic and "gerontogenic" agents. By way of introduction, a series of definitions of our subject material is given (aging, oncogenesis, proliferative homeostasis, point mutation, chromosomal mutation, epimutation, mutagens, clastogens, aneugens, gerontogens). There follows a defense of the view that there is a tight coupling of abnormalities in proliferative homeostasis (including atrophies, hyperplasias, benign neoplasias and malignant neoplasias) with intrinsic biological aging. This view differs from those of other authors who either: 1) believe that, to qualify as a bona fide component of aging, the phenotype in question (in this case, neoplasia) must be "genetically programmed" or 2) insist that the rate of development of the neoplastic phenotype should parallel species-specific Gompertz kinetics for the survival of the population of organisms. After briefly reviewing the classification of chromosomal lesions, we consider evidence for constitutional genetic determinants of chromosomal stability, oncogenesis, and some other aspects of the senescent phenotype, both with respect to interspecific and intraspecific differences. The discussion will include the recent evidence characterizing a human segmental progeroid syndrome (Werner's syndrome) as a deletor mutator strain. A summary of research on environmental chemical clastogens and aneugens is given, showing both discordances and concordances of such assays with assays for point mutagens. An analysis of the literature indicates that there is no statistical evidence for the positive correlations when substances showing effects only at comparatively high concentrations (greater than 1 mM) are excluded from the analysis. Brief mention is also made of the roles of viral agents and ionizing radiation in the genesis of chromosomal mutations. Finally, some possible pathogenetic mechanisms common to chromosomal mutagenicity, oncogenicity and gerontogenicity are considered, including chemical free radicals (active oxygen species), DNA transposition, DNA amplification, DNA glycation, virally induced cell fusion, posttranslational modifications of centromeric and mitotic spindle proteins, and alterations in the metabolism of telomeric DNA. PMID- 1859101 TI - Two dozen current problems in neuroimmunomodulation, aging, and cancer research; the second Stromboli cocktail; further rambunctious remarks. PMID- 1859102 TI - DNA processing, aging, and cancer. The impact of new technology. PMID- 1859103 TI - Longevity and heredity in humans. Association with the human leucocyte antigen phenotype. AB - Several arguments support the idea of a link between longevity and heredity, both in experimental animals and in the human species. In mice, genes in the major histocompatibility complex (MHC) are associated with a significant effect on life span. Results of analogous studies in man are confusing and contradictory. We have therefore investigated the question of an association of the human leucocyte antigen (HLA) and longevity in a large and ethnically homogeneous population. Our study population consisted of all 964 available inhabitants aged 85 years and over in the Dutch community of Leiden (pop. 104,000). Our control group comprised 2444 young inhabitants, aged 20-35 years, with an identical ethnic and demographic background. In addition, control groups of different age-brackets from the same region were used. Two antigens differed in frequency: HLA-B40 was lower and HLA-DR5 was higher in the group of 85 years and over, as compared to the control group, aged 20-35 years. Both differences were more evident in females. No major disease associations with HLA-B40 or HLA-DR5 have been reported. It is unlikely that these results are a chance observation: the overall similarity of the HLA pattern of the old and young age groups is a confirmation of their identical ethnic and demographic background and the changes as observed in the different age-groups were gradual. The biological meaning of these results is still unclear. PMID- 1859104 TI - In vivo probing of the brain cholinergic system in the aged rat. Effects of long term treatment with acetyl-L-carnitine. AB - The regulation of acetylcholine (ACh) release by the different subtypes of muscarinic (M) receptors in the hippocampus of freely-moving Fischer and Sprague Dawley rats, was investigated. Atropine (10 mumol/kg i.p.) induced a pronounced increase of ACh release (+400% over basal values) in the hippocampus of young rats (3 months) while the effect was drastically reduced (+100% over basal values) in old rats (24 months). The preferential M2 antagonist AF-DX 116 (50 mumol/kg i.p.) showed similar effects in young and old rats being, furthermore, 10 times less potent than atropine. The preferential M1 antagonist pirenzepine (50 mumol/kg i.p.) was even less potent than AF-DX 116 in enhancing ACh release in young rats, while the effect was more pronounced in the old ones. Therefore, the effect of the preferential M3 antagonist 4-DAMP was studied. 4-DAMP 10(-6) M, dissolved in the Ringer solution perfusing the hippocampus, induced an enhancement of ACh release (+200% and +70% over basal values, in young and old rats, respectively) which was comparable to that obtained after atropine at the same concentration. AF-DX 116 and pirenzepine, on the other hand, were by far less potent. Six months' pretreatment with acetyl-l-carnitine (ALCAR) reduced the significant differences between young and old rats in the release response after M1 and M3 receptor antagonists. Taken all together, these findings indicate that the regulation of ACh release, at least in the hippocampus, is mainly through the M3 receptors subtype of muscarinic receptors and that this subtype is the most involved in the aging process. Moreover, the ability of ALCAR to preserve the receptor-mediated functional ACh release response with respect to old animals suggests that ALCAR could be utilized in the amelioration of receptor functionality in the aging brain. PMID- 1859106 TI - [Ultrasound endoscopy in colonic and rectal disease]. PMID- 1859105 TI - Reactive capacities of the central nervous system in physiological aging and senile dementia of the Alzheimer type. PMID- 1859107 TI - [Feminising testicular tumors]. PMID- 1859108 TI - [Immediate breast reconstruction]. PMID- 1859109 TI - [Resection of the portal vein in pancreatectomy for cancer: technical considerations. Apropos of 4 cases]. AB - Out of 150 carcinomas of the pancreas operated from 1970 through 1989, 50 pancreatectomies were performed, including 4 cases of segmental resection of portal vein with total pancreatectomy (2 cases) or duodenopancreatectomy (2 cases). The technical procedure is described and discussed. Segmental resection of portal vein is rare in our experience and has been always performed out of necessity because of the over estimation of the resectability. However, mortality and post-operative stay are not increased. PMID- 1859111 TI - [Perforated peptic ulcer. Immediate results of therapeutic strategy]. AB - The aim of this study was to evaluate of logical program for the management of patients with perforated peptic ulcers. The case records of 75 consecutive patients were reviewed. The average age of the patients was 52 years. Ten patients were older than 80. The logical program was based on preoperative risk factors (concurrent medical illness, preoperative shock, and longstanding perforation more than 48 hours), history of chronic ulcer symptoms, and in selected cases, spontaneous seal on X-Ray gastroduodenogram with a water soluble contrast medium. The program was applied in 75% of cases and not applied in 25%. Out of 9 post-operative deaths (12%), 3 had a surgical cause: leakage of the suture with dehiscence in two cases. The mortality increased progressively with increasing of number of risk factors: 0%, 10% and 55% in patients with no, one, and two or three risk factors respectively. These findings constitute a validation of the predictive factors of death proposed by Boey et al. A logical program for the management of patients based on results of such multifactorial studies on risk factors, and on results of randomized prospective controlled studies may be applied in almost all patients. Our results also suggest that the quality of the perforation suture, and of the abdominal closure, especially in old and obese patients, are the most important factors to decrease the mortality. PMID- 1859110 TI - [Intestinal ischemia after surgery of the infrarenal aorta. Apropos of 13 cases]. AB - Ischemic damage of the gastrointestinal tract following aorto-iliac surgery was estimated in a retrospective study. Between 1984 and 1988, we observed 13 cases of intestinal ischemia from a total of 416 surgical patients (3 per cent): 7 cases of full-thickness necrosis and 6 cases of transient ischemia. They represent 23 per cent of complications in ruptured aneurysmal surgery, 2.8 per cent in elective aneurysmal surgery, and 1.6 per cent in operations for obstructive lesions. All deaths (5/13) followed necrosis. Diarrhea, sometimes bloody, was the main symptom. Its sensitivity was 70 per cent, and its specificity was 98 per cent. Leukocytosis (greater than 10000/mm3), was noted in 70 p. cent of the cases of ischemia. The diagnosis was established by colonoscopy in 7 cases and by surgical examinations in 6 cases. The endoscopic injuries were ulcerations, punctate hemorrhages, and pseudomembranes localized in the sigmoid (77 p. cent), left colon (38 per cent) and small bowel (15 per cent). Of 13 patients, 6 developed intraoperative hypotension. This study confirms the gravity of intestinal ischemia after aortic surgery. In high risk patients (ruptured aortic aneurysm, intraoperative hypotension, postoperative diarrhea) endoscopy offers the possibility of early diagnosis and appropriate treatment. PMID- 1859112 TI - [Aneurysms in various segments of the hepatic artery. Treatment by resection]. AB - The authors report two cases of aneurysms of the hepatic artery, one of which, with a intrahepatic localisation, was complicated by rupture and infection. The etiology was atherosclerotic in the case involving the main trunk of the hepatic artery, and polyarteritis nodosa in the case with intrahepatic involvement. Both were resected; the extrahepatic aneurysm was excised and a venous graft inserted, whereas in the one with intrahepatic involvement, right lobectomy was performed. On the basis of these cases, the authors discuss the various etiologies and the problems related to the indications and surgical techniques for aneurysms of the main trunk of the hepatic artery and those of its intrahepatic branches. PMID- 1859113 TI - [Comparative study of the treatment of fractures of the head of the radius by resection or by Swanson's silastic implant]. AB - The authors report 62 fractures of the head of the radius treated either by excision or silastic implant arthroplasty. Fifty-two patients were reviewed with a mean follow-up period of 5 years (range 1 to 13). Of 22 prosthetic replacements, 12 were satisfactory while of 30 excisions only 10 were rated good or excellent. Excision usually yielded valgus deformity of the elbow (range 9 to 35 degrees) and with a risk of shortening of the radius. Range of flexion extension was identical after both procedures but pronation supination was better after prosthesis replacement (78/70) than after radial head excision (65/60) 3 fractures of the implant were found at 6, 9 and 10 years postoperatively; only one of them was associated with pain and required removal of the loose fragments. PMID- 1859114 TI - [Intestinal intussusceptions in adults. Apropos of a case of spontaneous colo colonic intussusception]. AB - A case of idiopathic colonic intussusception in a 39-year old woman is reported. The main features of the disease are reviewed: the clinical presentation may be subacute or chronic, diagnosis is based on ultrasonography and water-soluble contrast media enema. Because of the frequency of malignancy primary resection in the treatment of choice. PMID- 1859116 TI - [In favour of cecostomy]. PMID- 1859115 TI - [Streptococcus pneumoniae thyroid abscess associated with a toxic nodular goiter. Apropos of a case]. AB - An unusual case of acute suppurative thyroiditis in association with toxic nodular goiter is reported by the authors. Surgical therapy was necessary due to the severity of the local and systemic inflammation induced by this association. PMID- 1859118 TI - [Pre-peritoneal inguinal hernioplasty using Rhodergon's prosthesis. Study of a series of 282 hernia operations]. AB - 282 acquired inguinal hernias in 183 adult patients were treated between 1974 and 1986 by means of a pre-peritoneal prosthesis. Posterior herniorrhaphy with reconstruction of the internal inguinal ring was associated with this procedure from 1981 onwards. 75% of the patients were reviewed with a mean follow-up of 58 months. Analysis of the results demonstrated a significant correlation between recurrences and the use of a single midline prosthesis for bilateral hernias and parietalisation of the spermatic cord and between septic complications and the use of a silicone-coated velvet prothesis, which subsequently had to be abandoned. Age, sex, obesity, type of hernia and a history of herniorrhaphy did not have any influence on the results. In group of 150 hernias treated with a single, lateralised Rhodergon prosthesis with a transprosthetic cord and reconstruction of the internal inguinal ring, the recurrence rate was 1.3% (2 cases) and the deep infection rate was 0.6% (1 case). Apart from early recurrences due to technical errors, the long-term efficacy of this technique appears to be permanent. PMID- 1859117 TI - [Hydatid cysts of the spleen: splenectomy or conservative surgery?]. AB - Conservative surgery of the spleen has become very popular. The authors report 36 cases of splenic hydatid cysts. This third site of hydatid disease is frequently associated with few symptoms and clinical examination only reveals splenomegaly, which has typical features on ultrasonography. Twenty-four splenectomies were performed with a mortality of 8.3% and a morbidity of 37.5%, while 12 resections of the roof of the cyst were performed with no mortality and a morbidity of 16.6% after a follow-up of 2 to 13 years. The authors consider that resection of the roof of the cyst constitutes of operation of choice, as it is conservative and safe, regardless of the anatomical conditions. PMID- 1859119 TI - [General epidemiology of arterial diseases: what is a risk factor?]. PMID- 1859120 TI - [Symposium: arterial aging--fundamental clinical and therapeutic aspects. Bordeaux, January 25-26, 1990. Part 1]. PMID- 1859121 TI - [Epidemiology and molecular genetics of atherosclerosis]. PMID- 1859122 TI - [Endothelium and aging of the arterial wall]. PMID- 1859123 TI - [Blood platelets and the elderly. Relation to the arterial wall and hemostasis]. PMID- 1859124 TI - [Aging of the arterial wall: endothelium, thrombosis and fibrinolysis]. PMID- 1859125 TI - [The factors of relaxation and contraction produced by the vascular endothelium. Effect of aging and the cardiovascular risk factors]. PMID- 1859126 TI - Endothelium and inflammation. PMID- 1859127 TI - [Eicosanoids and arterial aging]. PMID- 1859128 TI - [Proliferation of the arterial smooth muscle cells and aging]. PMID- 1859129 TI - [Elastin and arterial aging]. PMID- 1859130 TI - [Role of the adventitial innervation in establishing and maintaining the structural and functional properties of the arterial wall. Effects during aging]. PMID- 1859132 TI - [Retinal arterial aging]. PMID- 1859131 TI - [Microcirculation and aging]. PMID- 1859133 TI - [Cerebral vascular aging (excluding innervation)]. PMID- 1859134 TI - [Renal senescence]. PMID- 1859135 TI - [Arterial aging and lower limb arteriopathy]. PMID- 1859136 TI - [Symposium: arterial aging--fundamental clinical and therapeutic aspects. Bordeaux, January 25-26, 1990. Part 2]. PMID- 1859137 TI - [Aging of the lower limb arteries: methods of study]. PMID- 1859138 TI - [Role of mechanical factors in the phenomena of arterial aging associated to human hypertension]. PMID- 1859139 TI - [Hypertension and aging. Prognosis and treatment of the increase in blood pressure]. PMID- 1859140 TI - [Role of free radicals in aging and anti-oxygen treatment]. PMID- 1859141 TI - [Converting enzyme inhibitors in arterial hypertension]. PMID- 1859142 TI - [Calcium antagonists and vascular aging]. PMID- 1859143 TI - [Regulation of blood cholesterol]. PMID- 1859144 TI - [Serotonin and arterial aging]. PMID- 1859145 TI - [Therapeutics and arterial aging. Antiaggregants]. PMID- 1859146 TI - [Heparin and the arterial wall]. PMID- 1859147 TI - [Unstable angina and infarction without Q wave treated with verapamil: value of the early exercise test]. AB - Twenty patients aged 56.8 +/- 10 years, hospitalised for unstable angina (12 cases) or infarct without Q wave (8 cases) were treated with IV heparin, aspirin and oral verapamil. The clinical syndrome was controlled by verapamil in 16 cases out of 20 (80% of cases) at the dosage of 360 mg/d in 14 patients and of 480 mg/d in two. An exercise ECG, limited by symptoms, was obtained in 18 patients (90%) between the 8th and 12th day. Coronary arteriography was considered to be indicated in three sets of circumstances: recurrence of angina resistant to nitroglycerin, positive exercise ECG with verapamil, persisting despite triple therapy or strongly positive exercise ECG (total duration less than or equal to 6 minutes). An infarct complicated the early course in 4 patients (20%): twice following angioplasty, once following exercise ECG (spastic angina) and once during triple therapy (refractory angina). Hospital and mid-term (18 +/- 6 months) mortality was nil. With verapamil, the absence of recurrence of angina together with a negative exercise ECG enabled the identification of a large group of patients (40%) with a low risk of a subsequent major accident and in whom early and routine coronary arteriography is probably not indispensable. PMID- 1859148 TI - [Dobutamine: mechanisms of action and use in acute cardiovascular pathology]. AB - High levels of circulating catecholamines associated with heart failure down regulate cardiac beta-receptors, with a more pronounced effect on beta-1 receptors, leading to impaired inotropic effect. The use of exogenous inotropic agents is therefore a logical therapeutic approach in heart failure. Dobutamine is a synthetic catecholamine that acts on alpha-1, beta-1 and beta-2 adrenergic receptors. In the heart, the stimulation of these receptors produces a relatively strong, additive inotropic effect and a relatively weak chronotropic effect. In the vasculature, alpha-1 agonist activity (vasoconstriction) balances the beta-2 agonist effect (vasodilatation). In clinical use, dobutamine has a rapid onset of action and a short half-life. It increases myocardial contractility, while the reflex reduction in sympathetic tone, in response to augmentation of stroke volume, leads to a decrease in total peripheral resistance. The expected hemodynamic effects are an increase in cardiac output and a decrease in systemic vascular resistance without significant change in arterial pressure or heart rate. In acute cardiac failure state with elevated afterload pressures, resulting from myocardial dysfunction, dobutamine therapy remains, nowadays, the reference. PMID- 1859149 TI - Ideas towards audit in clinical biochemistry. PMID- 1859151 TI - Calcium and phosphorus metabolism in the premature infant. AB - During the last trimester of pregnancy, there is a sixfold increase in fetal calcium and phosphorus accumulation. Unsupplemented human breast milk may not provide sufficient calcium and phosphorus for the rapidly growing preterm infant to match the accumulation that should have taken place in utero and to permit normal bone mineralization. Rickets of prematurity may present clinically between the 6th and 12th postnatal week. The clinical diagnosis may be confirmed using simple biochemical tests. Inadequate mineral substrate intake, particularly of phosphorus, is the most common cause, although a delay in the maturation of the renal enzyme, 1-alpha hydroxylase, with low plasma concentrations of 1,25 dihydroxyvitamin D, may also occur. The biochemical response to treatment can be determined by documenting a fall in plasma alkaline phosphatase activity and a rise in plasma phosphate concentration and urinary phosphate excretion. PMID- 1859150 TI - The analysis of bilirubin in serum. AB - The most widely used methods for the assay of total bilirubin in serum are based on a coupling reaction with various diazo dyes in the presence of an accelerating agent. The 'direct' reaction, without accelerator, gives a good estimate of the conjugated and protein bound (delta) species of bilirubin only if carefully standardized reaction conditions are used. Enzymatic methods based on bilirubin oxidase appear to give similar results, for both total and direct bilirubin, and through difficult to calibrate, spectrophotometric methods can also give reliable results for total bilirubin at the higher concentrations seen in neonates. More sophisticated HPLC or dry-slide techniques are required for the specific assay of the various conjugated and protein-bound species of bilirubin in serum. PMID- 1859152 TI - Development and evaluation of the simultaneous determination of sweat sodium and chloride by ion-selective electrodes. AB - A method for the simultaneous determination of sweat sodium and chloride was developed and evaluated using a Monarch 2000 centrifugal analyser with ion selective electrodes. In order to measure sodium and chloride in diluted sweat samples and sweat paper eluates an analytical working range of below 10 mmol/L was required. This was achieved by modification of the Monarch ISE software parameters for urine electrolytes together with the use of calibrators within this range. Evaluation of the method has included linearity, recovery and precision studies and the correlation between ion-selective electrode and flame photometry for sweat sodium and between ion-selective electrode and a continuous flow method for sweat chloride. Of the patients studied so far, there has been good discrimination in sweat electrolytes between those with and without cystic fibrosis. PMID- 1859153 TI - Use of a silver-enhanced gold-labelled immunoassay for detection of antibodies to the human immunodeficiency virus in whole blood samples. AB - A silver-enhanced gold-labelled immunosorbent assay (SEGLISA) for the detection of antibodies to the immunodeficiency virus (HIV) in whole-blood samples is described. This new non-isotopic, non-enzymic immunoassay incorporates use of solid phase viral antigens which bind any HIV antibodies present in the test sample. The antigen/antibody complex is then detected by gold-labelled anti human immunoglobulin G (IgG) followed by silver amplification. We found that whole blood samples give false positives when using a horseradish peroxidase label, whereas the SEGLISA correctly identified 50 HIV antibody positive samples and 50 HIV antibody negative samples when using whole blood. The use of whole blood collected on filter paper is also described. The SEGLISA has good precision (CV = 7.5%) and sensitivity. PMID- 1859154 TI - A two-site immunoradiometric assay for PTH(1-84) using N and C terminal specific monoclonal antibodies. AB - We report the development of a two-site immunoradiometric assay for PTH(1-84) based on two site-specific monoclonal antibodies--3B3 (radiolabelled antibody) specific for PTH(1-34) and ESQ1 (on solid phase) specific for PTH(74-84). Antibody 3B3 is sensitive to the oxidation of the methionine residues in PTH(1 34) therefore hydrogen peroxide (0.1 M) is added to the incubation mixture. Validation studies confirm quantitative recovery of both oxidized and reduced PTH(1-84). The assay has a minimum detection limit of 0.5 pmol/L and a range of 1.5-250 pmol/L with an intra-assay CV of less than 10% (2.8-250 pmol/L less than 5% CV). Studies on clinical samples indicate good discrimination between normal subjects (mean 2.21; range 1.0-5.0 pmol/L) and patients with primary hyperparathyroidism (mean 21.0; range 5.8-100 pmol/L) who in turn are well separated from patients with hypercalcaemia of malignancy (14/18 less than 0.5 pmol/L). PMID- 1859156 TI - Transferrinuria in type 2 diabetes: the effect of glycaemic control. AB - Urinary excretion rates of transferrin, albumin, N-acetyl-beta-D-glucosaminidase (NAG) and alpha-1-microglobulin (A1M) were measured in type 2 (non-insulin dependent) diabetic patients at diagnosis and after 6 and 12 weeks treatment. Initially 21 (53%) patients had elevated transferrin excretion rates. The proportion of patients with raised transferrin excretion rates fell to 30% at 6 weeks and 20% at 12 weeks with treatment of diabetes. At diagnosis 11 (28%) patients had elevated albumin excretion rates and 10 of these had elevated transferrin excretion rates. After 6 weeks treatment only six (15%) had elevated albumin excretion rates and by 12 weeks this number had fallen to four (10%). NAG and A1M levels also fell with treatment of diabetes. There were correlations between the transferrin excretion rate and albumin excretion rate (r = 0.86, P less than 0.0001), transferrin excretion rate and NAG (r = 0.46, P less than 0.0001), and transferrin excretion rate and A1M (r = 0.55, P less than 0.0001) at each visit. There were weaker correlations between the albumin excretion rate and A1M and NAG at each visit. The correlations between the transferrin excretion rate and markers of tubular function (NAG and A1M) suggest that tubular dysfunction may play a part in renal loss of transferrin in diabetes mellitus. There were no differences in transferrin excretion rates between patients with and without evidence of complications. PMID- 1859157 TI - Improved procedure for the second-derivative spectrophotometric analysis of carboxyhaemoglobin. AB - We describe a modification of the second-derivative spectrophotometric assay for carboxyhaemoglobin in blood. Using the original procedure we have often observed a time-dependent change in the signal leading to unreliable results. By using phosphate-buffered-saline (pH 7.4) instead of ammonia to dissolve the deoxygenating agent (sodium dithionite), we obtained stable and reproducible second-derivative signals from which the percentage carboxyhaemoglobin in the patients' samples can be calculated. PMID- 1859155 TI - Preanalytical errors in ionized calcium measurements induced by the use of liquid heparin. AB - The use of heparin in a liquid form to measure ionized calcium (Ca++) in plasma or whole blood can induce preanalytical errors by dilution and by changing the original Ca++ value by binding or by re-equilibration with calcium in the anticoagulant solution. To quantify these errors, Ca++ was measured on serum pools under different sampling conditions. Incomplete syringe filling and specimen volume/syringe nominal volume ratio effects were tested. Syringes were rinsed with saline to yield pure dilution effects, with sodium heparinate to study binding and with calcium-titrated heparinate to evaluate 'calcium distortion'. Detailed tables provide percentage error values for all sampling conditions. Dilution errors could reach -5% and binding was always important (-14 to -50%). Distortion was minimal around 1.25 mmol/L but could reach -4% for high and +8% for low Ca++ values. Errors increased when syringes were not filled to their nominal volume, especially with small-sized specimens. PMID- 1859158 TI - Evaluation of the Helena REP automated electrophoresis instrument for the measurement of glycated haemoglobin. PMID- 1859159 TI - The effect of semen contamination on the concentration of low molecular weight proteins, albumin and total protein in male urine. PMID- 1859160 TI - Differential response of serum alkaline phosphatase and serum osteocalcin in Paget's osteosarcoma. AB - Serum osteocalcin did not show any response to the onset of osteosarcoma in Paget's disease of bone whereas serum alkaline phosphatase increased rapidly. This suggests that osteocalcin is not useful in the diagnosis and management of Paget's osteosarcoma and does not reflect the same osteoblastic processes in bone as serum alkaline phosphatase. PMID- 1859161 TI - Influence of monoclonal immunoglobulins on methods for inorganic phosphorous. PMID- 1859162 TI - Delayed diagnosis of Addison's disease. PMID- 1859163 TI - Maternal hypothyroxinemia: psychoneurological deficits of progeny. AB - Maternal thyroid function was evaluated clinically, by reproductive history, and by serial measurements of serum butanol-extractable iodine (thyroxine-like iodine), two before and two after 24 gestational weeks during 1,349 pregnancies. Three percent of the women were hypothyroxinemic. Developmental, intellectual, and motor abilities of progeny born to (Group I) 210 euthyroxinemic, (Group II) 15 hypothyroxinemic given adequate thyroid replacement therapy, and (Group III) 21 inadequately treated hypothyroxinemic women were compared. The groups of mothers exhibited no significant differences in intelligence, years of education, or chronological age. Mean developmental and intellectual scores at eight months, four and seven years of Group II progeny evidenced remarkably consistent similarity to scores of siblings and controls. At each age, mean developmental and intellectual scores were lower for Group III progeny, and motor scores of the latter were lowest. Some progeny of Group II mothers, treated only after 12 or 29 weeks, failed the ball catch and line walk tests; some had strabismus and other ocular disturbances. Could these deficits have originated with maternal hypothyroxinemia during first semester weeks before the thyroid-pituitary axis matures? Now in 1990-1991, early findings fit into the modern concepts of significant maternal gestational transfer of thyroxine to the fetus. The authors encourage prenatal and/or early gestational screening for maternal hypothyroxinemia and urge prescription of adequate thyroid replacement therapy for hypothyroxinemic women. PMID- 1859164 TI - Carrageenan-induced intestinal injury: possible role of oxygen free radicals. AB - There is a growing body of evidence that implicates oxygen free radicals in a wide variety of inflammatory conditions in various body systems including the gastrointestinal tract. The purpose of this study was to ascertain whether or not oxy-radicals play a role in carrageenan-mediated intestinal injury. Allopurinol, superoxide dismutase-polyethylene glycol, and dimethyl sulfoxide, respectively, were administered to the carrageenan rat model for 30 to 32 days. Collectively, all three drugs attenuated the carrageenan-mediated injury as shown by four indices of intestinal damage: ulceration (p = 0.0007); abnormal villous pattern (p = 0.0002); degree of inflammation (p = 0.0001); and extent of inflammation (p = 0.0025). Dimethyl sulfoxide appeared to be the least efficacious of the three drugs. The results suggest that oxygen free radicals play a role in carrageenan mediated intestinal injury, and that one of the sources of these oxy-radicals may be the intestinal macrophage. PMID- 1859165 TI - Human immunodeficiency virus and the placenta. Current concepts of vertical transmission in relation to other viral agents. AB - The prevalence of human immunodeficiency virus (HIV) infection in women of the reproductive age group has been increasing and, with it, vertical transmission of the virus to their infants. It is currently believed that intrauterine transplacental infection of the fetus is the most important mechanism of vertical transmission; thus, a recent focus of investigation has been on the role of the placenta in maternofetal HIV infection. However, the mechanisms by which infectious agents cross the placenta to infect the fetus remain largely unknown. Some lessons of possible relevance to issues related to vertical HIV transmission may be gained by reviewing the experience with other agents that can affect the fetus and newborn. This communication examines current virologic and clinicopathologic features of perinatal HIV infection in light of concepts of placental and fetal infection with other viral agents in an attempt to find a model of vertical HIV transmission. PMID- 1859167 TI - Creatine kinase MB measured by fluorometric enzyme immunoassay and immunochemiluminescence. AB - Creatine kinase MB (CK-MB) was measured in serum by a fluorometric enzyme immunoassay on the Stratus analyzer and by an immunochemiluminometric assay using the Ciba Corning Magic Lite System. Both methods were standardized against purified CK-MB, with Stratus underestimating by 20 percent and Magic Lite overestimating by 28 percent. The assays proved sensitive and linear; however, at a CK-MB concentration of 7.0 micrograms per L, Stratus gave unacceptable inter assay precision. No cross-reactivity was observed with CK-MM or CK-BB and elevated triglycerides, bilirubin, and hemoglobin did not interfere. Correlations with an immunoradiometric assay (Embria), using 522 samples, gave: Stratus = 0.999 (Embria) -3.3; r = 0.969, and Magic Lite = 1.225 (Embria) -3.03; r = 0.971. When using Magic Lite, results from 40 acute myocardial infarction (AMI) patients gave a mean CK-MB value of 93.8 micrograms per L (range: 9.2 to 428 micrograms per L) at the peak of enzyme release and a mean value of 69.6 micrograms per L (range: 6.7 to 319 micrograms per L) when using Stratus. Both methods proved to be highly sensitive and specific in the diagnosis of AMI; however, the need for standardization of CK-MB assays is stressed. PMID- 1859166 TI - Pathological reactions in lung, liver, thymus, and spleen of rats after subacute parenteral administration of nickel sulfate. AB - Male Fischer-344 rats (10 to 12 rats per group) were given 14 i.m. injection of nickel sulfate (NiSO4) over a period of 26 days in order to delineate the two year survival, body weight curves, hematocrit responses, and histopathological reactions, including carcinogenesis. Group A (vehicle controls) received the NaCl vehicle; Groups B, C, and D received NiSO4 solution at dosages of 63, 83, or 125 mumol per kg, respectively. Rats in Group D all died during the period from 4 to 32 days after the first injection; survival of rats in Groups B and C did not differ significantly from the controls (Group A). No differences were found at any time between the mean body weights or blood hematocrits of the NiSO4-treated groups vs. the controls. In Group D, histopathological lesions of the lung, liver, thymus, and spleen were consistently observed; these lesions were most severe in rats that died during the period from 22 to 32 days after the first injection. The lungs showed proliferation of alveolar lining cells, thickening of the alveolar wall, and proteinaceous alveolar exudate. The livers showed microvesicular steatosis, and necrotic hepatocytes were scattered throughout the lobules. Degeneration of lymphocytes, with pyknosis and karyorrhexis, was observed in the thymic cortex and the white pulp of the spleen. At necropsy, no significant differences were found between the NiSO4-treated rats of Groups B and C and the controls (Group A). No sarcomas or other neoplasms occurred near the injection sites in NiSO4-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859168 TI - [A comparative prospective study of an edrophonium test and an esophageal balloon distension test in 78 patients with non-coronary angina and 12 healthy controls]. AB - The aim of this study was to compare the most current tests used for the diagnosis of esophageal angina-like pain: manometry, balloon distension, edrophonium provocation. METHOD: 78 patients with angina-like pain, who had normal coronary arteriograms, and 12 healthy controls were prospectively evaluated with esophageal manometry, esophageal balloon distension, according to Barish's method (2), edrophonium provocation and 3 h pH-monitoring. Provocation tests were considered positive if they reproduced the angina-like pain. RESULTS: basal manometry was abnormal in 23 patients (29%); nutcracker esophagus; 8, achalasia; 1, diffuse esophageal spasm: 1, hypertensive LES: 2, non specific motility disorders: 5, It was abnormal in 1 healthy control (1 nutcracker esophagus). Edrophonium provocation was positive in 19 patients (24%) and in none of the controls. Balloon distension was positive in 33 patients (42%) and none of the controls, but 3 controls experienced a back pain at 7, 9 and 9 cc. Balloon distension was more sensitive than edrophonium provocation (p less than 0.001). There was no correlation between the results of the basal manometry and those of balloon distension and no correlation between pH monitoring and balloon distension. 1) Balloon distension is the most sensitive test and should be used at first. 2) If balloon distension is negative edrophonium provocation can be useful because the pain mechanism is different. 3) Some controls can experience a back pain without irradiation, then balloon distension must be considered positive only if it strictly reproduces the spontaneous angina-like pain. PMID- 1859169 TI - [Epidemiology, physiopathology and natural history of diverticulosis of the colon]. PMID- 1859170 TI - [Medical attitude toward colonic diverticulosis]. PMID- 1859171 TI - [Elective surgical treatment of colonic diverticulosis]. AB - In a retrospective study from 1978 to 1990, 143 patients had elective surgery for colonic diverticular disease. Surgical indications were: uncomplicated diverticulitis (128), functional discomfort (6), suspicion of associated neoplasia (6), bleeding (3). The overall mortality is 1/143 (0.6 p. cent). 3 patients (2.2 p. cent) had to be reoperated for anastomotic fistula with peritonitis. Definitive re-establishment of digestive continuity was done in 139 patients (98.6 p. cent). Our results suggest that surgery is to be widely indicated for diverticular disease. Resection must be performed in every patients presenting with an history of two or more acute recurrences, with a fistula, and when clinical and/or radiological abnormalities continue after a first acute crisis. PMID- 1859172 TI - [The scanner in diverticular disease]. PMID- 1859174 TI - [Long-term results of endoscopic neodymium YAG (Nd:YAG) laser treatment of vascular malformations of the digestive tube]. PMID- 1859173 TI - [Surgical treatment of acute complications of diverticular disease]. PMID- 1859175 TI - Nonaneurysmal subarachnoid hemorrhage. PMID- 1859176 TI - The clinical course of perimesencephalic nonaneurysmal subarachnoid hemorrhage. AB - We studied the early clinical course of 65 patients with perimesencephalic (nonaneurysmal) subarachnoid hemorrhage. None of the patients rebled; none had delayed cerebral ischemia; and only 3 patients (5%) developed clinical signs of acute hydrocephalus, 2 requiring ventricular shunting. Hyponatremia and electrocardiographic changes were found in the same proportions as in patients with aneurysmal rupture. All patients had a good outcome after 3 months. To control for the influence of the relatively small amount of cisternal blood in perimesencephalic hemorrhage on the absence of delayed cerebral ischemia, we compared these 65 patients with 49 patients who had aneurysmal subarachnoid hemorrhage. This control group with aneurysms was selected according to a similar amount of cisternal blood, a comparable level of consciousness on admission, and absence of other factors known to increase the risk for delayed cerebral ischemia. We found that 4 of the 49 patients with aneurysmal hemorrhage developed delayed cerebral ischemia (Fisher's exact test, p = 0.03); therefore the relatively small amount of blood does not account for the absence of delayed cerebral ischemia in perimesencephalic hemorrhage. Patients with a perimesencephalic pattern of hemorrhage and a normal angiogram should be considered to have a distinct subset of subarachnoid hemorrhage and should be excluded from future treatment trials of patients with subarachnoid hemorrhage. PMID- 1859177 TI - Benign familial neonatal convulsions: evidence for clinical and genetic heterogeneity. AB - The gene for autosomal dominant "benign" familial neonatal convulsions, a transient, primary epilepsy of infancy, has recently been assigned to chromosome 20q. To determine whether this disorder is genetically heterogeneous, we performed linkage analysis in two previously unreported pedigrees with benign familial neonatal convulsions in which clinical heterogeneity was evident. There were 14 affected persons in the first family, and none had seizures (febrile or afebrile) after the age of 2 months. The second family had 13 affected individuals and 2 obligate carriers; seizures frequently did not remit until 6 to 24 months, febrile convulsions occurred in at least 2 patients, apparent audiogenic seizures occurred in 4 patients, and 1 individual had refractory epilepsy until late adolescence. Linkage studies with the chromosome 20 markers D20S19 and D20S20 were performed in both families. The resulting data favored linkage of the disease and marker loci in Family 2 by a maximum odds ratio of 45:1 at 6% recombination. In Family 1, however, the odds were greater than 20,000:1 against linkage at 10% recombination or less. We conclude that the syndrome of benign familial neonatal convulsions is clinically and genetically heterogeneous. Further study will be necessary to clarify the relationship between phenotype and genotype in this disorder. PMID- 1859178 TI - Immunocytochemical and virological characteristics of HIV-associated inflammatory myopathies: similarities with seronegative polymyositis. AB - We performed an immunoperoxidase study on muscle biopsy specimens from 19 patients with polymyositis who were seropositive for human immunodeficiency virus (HIV) (21 specimens) and 5 HIV-seronegative patients with polymyositis and compared the findings. A quantitative analysis of T cells and T-cell subsets, B cells, natural killer cells, interleukin-2 receptor-positive cells, and macrophages was performed on serial sections from all the specimens. Localization of major histocompatibility complex (MHC)-I and -II antigens, alpha and gamma interferon, and HIV antigens (p24, gp120, and gp41) was performed using specific antisera. In specimens from HIV-positive and seronegative patients, the predominant cell population was CD8+ cells and macrophages invading or surrounding healthy muscle fibers that expressed MHC-I antigen on their surface. The endomysial infiltrates in specimens from HIV-positive patients differed from those seen in specimens from the seronegative patients only by a significant reduction of the CD4+ cells (12.6 +/- 3.2% versus 21.1 +/- 4.2%). HIV antigens were seen in occasional interstitial mononuclear cells (but not in muscle fibers) in 6 of the 21 specimens from HIV-positive patients. Interferon was not localized. We conclude that the development of HIV-associated polymyositis does not appear to be related to direct infection of the muscle fibers by HIV but rather is due to a T-cell-mediated and MHC-I-restricted cytotoxic process, perhaps triggered by HIV. Because this immunopathological mechanism is common in both HIV-associated polymyositis and polymyositis alone, it is suggested that viruses may also be responsible in triggering polymyositis. PMID- 1859179 TI - Cold-induced brain edema and infarction are reduced in transgenic mice overexpressing CuZn-superoxide dismutase. AB - It has been proposed that oxygen-derived radicals, superoxide in particular, are involved in the alteration of blood-brain barrier permeability and the pathogenesis of brain edema following trauma, ischemia, and reperfusion injury. Using transgenic mice that overexpress the human gene for copper-zinc-superoxide dismutase, we studied the role of superoxide radicals in the blood-brain permeability changes, edema development, and delayed infarction resulting from cold-trauma brain injury. At 2 hours after a 30-second cold injury, cerebral water and Evans blue contents were reduced, respectively, from 80 +/- 0.2% and 132.7 +/- 12.9 micrograms/gm of dry weight for nontransgenic mice to 78.5 +/- 0.3% and 87.1 +/- 9.9 micrograms/gm of dry weight for transgenic mice. Infarction, as measured by 2,3,5-triphenyltetrazolium chloride staining, was reduced by 52% in transgenic brains. These data indicate that an increased level of superoxide dismutase activity in the brain reduces the development of vasogenic brain edema and infarction. Superoxide radicals play an important role in the pathogenesis of these lesions in cold-traumatized brain. PMID- 1859180 TI - Epidemiology of encephalitis in children: a 20-year survey. AB - Four hundred five children from the Helsinki area who were 1 month to 16 years old were treated for acute encephalitis at the Children's Hospital, University of Helsinki, from January 1968 through December 1987. Encephalitis occurred most commonly in children 1 to 1.9 years of age, among whom the incidence was 16.7 per 100,000 child-years. The incidence remained quite high until the age of 10 years, and then gradually declined to 1.0 per 100,000 child-years at the age of 15 years. Since 1983, when mumps, measles, and rubella vaccination eradicated the encephalitides associated with these microbes, the major associated agents have been varicella-zoster, Mycoplasma pneumoniae, and respiratory and enteroviruses. In infants younger than 1 year of age, the major agents were enteroviruses, herpes simplex virus, and the group of "others," whereas in older children, respiratory viruses and Mycoplasma pneumoniae, as well as varicella-zoster virus, dominated. In children aged 1 to 11 months, the causal agent could not be identified in one-half of all cases, whereas in children who were at least 10 years old, the etiology remained unknown in only one-fourth of cases. Male dominance was most evident in the 4- to 9-year age group. The difference in etiology between males and females was significant (p = 0.02); mumps and varicella were more common in boys, and adenovirus and Mycoplasma pneumoniae were more common in girls. The overall male-to-female ratio was 1.4:1. Characteristic seasonal variation occurred in encephalitides associated with mumps, measles, and entero- and respiratory viruses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859181 TI - Lhermitte-Duclos disease and Cowden disease: a single phakomatosis. AB - Two unrelated patients with macrocephaly, seizures, and mild cerebellar signs had a dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease). Both also had autosomal dominant Cowden disease as evidenced by facial, oral, and acral papules. In the two families, 9 sibs demonstrated the mucocutaneous lesions, thyroid disease, breast tumors, and ovarian tumors compatible with the diagnosis of Cowden disease. Some of the sibs also showed various degrees of neurological signs such as macrocephaly, mental retardation, seizures, tremor, and dysdiadochokinesia. Magnetic resonance imaging scans of sibs of one family demonstrated megalencephaly and other mild abnormalities. The occurrence of these two rare disorders in single patients is more than a coincidence, and the clinical findings in the combined condition establishes it as a new phakomatosis. PMID- 1859182 TI - Eosinophilia myalgia syndrome: I. Immunocytochemical evidence for a T-cell mediated immune effector response. AB - Specimens of muscle and fascia from 13 patients fulfilling the Centers for Disease Control criteria for the eosinophilia myalgia syndrome (EMS) were studied by quantitative immunocytochemical analysis. The immunolocalization of CD3, CD4, CD8, CD22, and CD56 markers, the gamma delta T-cell receptor, major histocompatibility complex (MHC) class I complex and class II antigens, and complement membrane attack complex (MAC) were examined. The distribution and relative proportions of T cells and T-cell subsets, B cells, macrophages, and eosinophils were determined at perivascular, perimysial, endomysial, and fascial sites of accumulation. At all sites, T cells were predominant, CD8+ cells outnumbered CD4+ cells 6- to 20-fold, and between 60 and 80% of T cells were activated. B cells and eosinophils each accounted for less than 3% of inflammatory cells. Very few cells expressed either the gamma delta T-cell receptor or natural killer cell markers. As in dermatomyositis (DM), MHC class I antigen complex expression was increased on many structurally normal muscle fibers, but in contrast to DM, microvascular MAC deposits were not a feature of EMS. The findings implicate a cellular immune response directed against a connective tissue component in EMS. PMID- 1859183 TI - The role of prolactin in autoimmune demyelination: suppression of experimental allergic encephalomyelitis by bromocriptine. AB - Several lines of evidence suggest that the anterior pituitary hormone prolactin has a stimulatory role on immune function and that pharmacological suppression of prolactin secretion with the dopamine-agonist bromocriptine suppresses both humoral and cellular immunity. Here, we describe the effects of prolactin suppression on the course of experimental allergic encephalomyelitis in female Lewis rats. Initiation of continuous bromocriptine treatment before immunization reduced both the severity and incidence of clinical signs of acute experimental allergic encephalomyelitis. Experimental allergic encephalomyelitis-immunized rats experienced a threefold rise in basal prolactin levels on day 4 after immunization and maintained elevated prolactin levels on day 10, before the onset of neurological signs of experimental allergic encephalomyelitis. Bromocriptine treatment reduced prolactin levels to those of sham-immunized rats. In vivo bromocriptine pretreatment inhibited splenic lymphocyte proliferative responses in vitro to the immunizing antigen and to concanavalin A. Moreover, bromocriptine therapy was protective when initiated 1 week after the initial immunization and was also effective in suppression of late disease. These results indicate that (1) prolactin levels are elevated after immunization and before the onset of experimental allergic encephalomyelitis, (2) bromocriptine inhibits both prolactin secretion and the severity of acute experimental allergic encephalomyelitis, and (3) inhibition is also present when treatment is begun after sensitization, suggesting an effect of prolactin on the effector limb of the immune response during experimental allergic encephalomyelitis. PMID- 1859184 TI - Serial gadolinium-enhanced magnetic resonance imaging scans in patients with early, relapsing-remitting multiple sclerosis: implications for clinical trials and natural history. AB - Six patients with early, mild, relapsing-remitting multiple sclerosis were studied with monthly gadolinium-enhanced magnetic resonance imaging scans for 8 to 11 months. Numerous enhancing lesions were observed irrespective of clinical activity. Four of the 6 patients had one or more enhancing lesions present on each examination. The other 2 patients had enhancing lesions noted in 7 and 9 of 11 months. In contrast, only two clinical exacerbations were observed during the study period. Neither the exacerbations nor other changes in symptoms or signs correlated with occurrence of the enhancing lesions. Enhancement generally persisted for less than 1 month. The opening of the blood-brain barrier as reflected by gadolinium enhancement on magnetic resonance imaging may represent ongoing disease activity in patients with mild, relapsing-remitting multiple sclerosis who are clinically stable. The frequency of these lesions appears to be sufficient to use as an outcome measure in clinical trials testing clinical efficacy in patients with early, relapsing-remitting multiple sclerosis. PMID- 1859185 TI - Temporal relationships between plasma and cerebrospinal fluid pharmacokinetics of levodopa and clinical effect in Parkinson's disease. AB - We studied the pharmacokinetics of levodopa and its metabolites in plasma and ventricular cerebrospinal fluid in 4 parkinsonian patients with indwelling Ommaya reservoirs placed at the time of previous adrenal-medullary to caudate nucleus transplantation. Cerebrospinal fluid levodopa levels were 11.9% of those in plasma. Motor performance and dyskinesia correlated more closely with the time course of the appearance of levodopa in the ventricular cerebrospinal fluid than with the plasma levodopa concentration and did not correlate with plasma 3-O methyldopa or cerebrospinal fluid 3-O-methyldopa or homovanillic acid. Our data confirm that the wearing off of the levodopa effect in patients with advanced Parkinson's disease is a function of drug concentration in the central nervous system. PMID- 1859186 TI - Central sleep apnea and arterial compression of the medulla. AB - We report a 5-year-old with central sleep apnea associated with compression of the medulla oblongata by abnormal looping of the left vertebral artery. The magnetic resonance imaging findings raise the possibility that compression of the respiratory center by an aberrant vertebral artery might cause central sleep apnea. PMID- 1859187 TI - Altered glucose metabolism in microvessels from patients with Alzheimer's disease. PMID- 1859188 TI - Intellectual functioning in treated Wilson's disease. PMID- 1859190 TI - Adenosine and seizure termination. PMID- 1859189 TI - Dysarthria--clumsy hand syndrome or homolateral ataxia and crural paresis? PMID- 1859191 TI - Carbamazepine and the heart. PMID- 1859192 TI - [Quantitative dermatoglyphic markers in fra-X-syndrome]. AB - Quantitative dermatoglyphic characters of fingers and palms of 61 male patients with fra-X-syndrome and 20 female heterozygote carriers were analysed and compared with the data from 84 male and 90 female normal individuals. Univariate and multivariate analysis of the data led to the following conclusions: 1. The fra-X-syndrome patients show higher ridge count and higher MLI value (increased transversality of the main lines), and lower a-b ridge counts than the controls. In addition to this, differences are observed also for the diversity and asymmetry measures. 2. Discriminant analysis as applied to the sexes separately, showed that 75% of males can be correctly classified in their group. However, the percent of correctly classified females is lower than the males; it is 70% (fra-X female) ad 64.4% (control female). 3. D2-matrix and the comparison of TFR C values support the hypothesis of X-chromosomal doses effect on the dermatoglyphics. PMID- 1859193 TI - [Factor 13 B (FSF) polymorphism in the Swiss population, with reference to European frequency gradients]. AB - Phenotype and allele frequencies of the coagulation factor 13 B (FSF B) of three Swiss populations (Northern Switzerland, upper Rhone valley and valley of Safien) have been determined after electrophoresis and passive immunoblotting and are discussed with respect to the geographical distribution and to the history of these populations. The populations of the upper Rhone valley and the valley of Safien reveal a closer genetical relationship obviously due to the migration of the antecedents of the recent Safier from the Rhone valley to the Safien valley from the 13th to 14th century. The allele frequencies of the Swiss German population fit rather well the North-South genetical cline which has to be considered in the light of the early settlement of Central Europe and of the numerous migrations thereafter. PMID- 1859194 TI - [Phenotype incidence of some hemo-genetic polymorphism markers in the Lower Rhine region (Kleve, Goch, Kalkar area)]. AB - In a sample of 262 individuals from the Lower Rhine region (Kleve, Goch, Kalkar: Germany) 27 hemogenetic polymorphisms have been studied. There were no significant differences in phenotype frequencies between the Lower Rhine and the Dusseldorf region. PMID- 1859195 TI - [Excavation in middle Iraq. Anthropologic results of findings from the thousand years before Christ]. AB - In the years from 1970 to 1985 the "Belgian Archaeological Expedition to Iraq" excavated the remains of the ancient cultural and commercial centers Sippar and Sippar Amnanum. In connexion with this work it was possible to remove twelve human skeletons from the Persian and Hellenistic Period which are described here. PMID- 1859196 TI - [Neanderthal markers of the frontal bone--a conspicuous Hallstatt cranium of the burial field Dietfurt/Oberpfalz]. AB - Between the skulls from early Iron Age cemeteries of the Hallstatt period (Beilngries, Dietfurt, Schirndorf and some other localities) in the Upper Palatinate (Bavaria) the skull Dietfurt 13/1 attracted attention because of its archaic traits at the viscerocranium and because of its extraordinarily large cranial capacity (1654 cm3). Such large cranial capacities were well known from Neandertals. Therefore this skull was examined for other neandertaloid traits: It was shown that the values for the angle of inclination and the vault-angle of the frontal bone fell into the neandertaloid range. With regard to the traits of the frontal bone Dietfurt 13/1 takes a more intermediate position between Homo sapiens sapiens and the Neandertals than the frontal bone from Hahnofersand, which is dated about 36.300 +/- 600 years B.P. (Brauer 1980). It is discussed, whether the specific traits of the frontal bone of Dietfurt 13/1 could fall within the variability of the subfossil Homo sapiens sapiens without postulating a phase of hybridization between Neandertals and anatomically modern man. Consequently, in the compilation of prehistorical skeleton-series more attention should be given to measures of the frontal bone. PMID- 1859197 TI - [Unexplained findings in anthropologic study material from Egypt. Addenda to Herodotus' "Historian", Lib. II, 86-88 and Egyptian "Sparagmos"?]. AB - The authors report on recently excavated mummified human remains from Buto and Minshat Abu Omar in the Nile Delta (Lower Egypt). There is evidence that besides the conventional mummification techniques described for example by Herodotus rather invasive methods have been applied, i.e. maceration and dissection of the soft tissue, partly followed by modelling the skeleton with a thin layer of mud. This practise remembers of certain mutilated anthropological material of predynastic origin discovered towards the end of the last century by W.M. Flinders Petrie, which additionally seems to show significant parallels to ancient Egyptian mythological and religious texts (Pyramid texts, Coffin texts, Book of the Dead, etc.). Probably the presented findings, dated between 700 B.C. and 400 A.D., must be explained as a local rebirth of an archaic but non-specific Egyptian custom, preceding the inauguration of mummification in Egypt. The main task of this paper is to introduce important new material and to ask those missions also involved in archaeological fieldwork in Egypt for paying special attention to this subject. PMID- 1859199 TI - [Results of computer-assisted studies of population structure and burial practices of adults of the late Roman burial ground in the Minshat Abu Omar (east Nile delta)]. AB - The results of 1448 skeletons met the requirements (database) for the completed examinations. Statistical correlations between situation of the skeletons in view of compass directions, position of the skeletons, grave type and mumification traces were calculated. More than 90% of the analyzed individuals were buried in west-east direction (head-feet). In 69% of all cases the skeletons were buried with their hands on or next to the pelvis. 98% of all mummies examined were found in the position hand/hands on shoulder. Special grave architecture was given in 15.8% of the examined individuals. The average life-expectancy for the group between 20 to 29 amounted to 14.65 years. The cluster-analysis showed clear differentiation of the male group in 3 to 4 subpopulations. For the female group a mathematical probability for 3 subpopulations was given. Connecting the data of cluster and burial types a significant distinction between the four male clusters - according to the distribution of the skeleton positions - could be seen. Within the female group a clear correlation between clusters and common characteristics could be found in 7 subgroups. Differentiated distribution was revealed in the different alignments of the skeletons. PMID- 1859198 TI - [Paleodemographic and cultural historical studies of skeletal remains of the pre- and early dynasty necropole in Minshat Abu Omar (east Nile delta)]. AB - The pre- and early dynastic necropole near by Minshat Abu Omar can be dated (Carbon dates) in the time from 3300 till 2900 B.C. Till now, there were 418 graves investigated. The dead people were buried in left or right flexed position. High salt concentration in sand destroyed the bone material extraordinary, so that morphometric analysis could not be done. The determination of sex and/or age was possible for 87.08% of the individuums. The average of the life-span was about 26 years. The village consists of 20 till 50 huts with 107 till 120 inhabitants. PMID- 1859200 TI - [Stress on the human body when falling into a rope harness and its sequelae]. AB - The stress during holding a fall of a climber was evaluated in practical tests with human subjects. Depending on the situation of the fall forces up to 4 kN are acting on the body through the harness. With extreme rope friction at the rock and running belays the forces can increase up to 6.5 kN. These forces depend on the method of belay and the situation of the fall and are mostly independent from the weight of the climber. Therefore light climbers are subjected to greater deceleration forces than heavy climbers. For a given force of 4 kN the biodynamics during impact is shown. If only a seat harness, surrounding only the pelvis, is used, the bending loads on the spine exceed under certain circumstances the human tolerance considerably. Whiplash effects, head down falls or severe pressure loads on the viscera can also occur. Besides these acute injuries chronic injuries of ligaments of the spine and the invertebral discs can occur because every stress overcharging the muscles must be taken up by the ligaments. PMID- 1859201 TI - [Biology of human speech communication]. AB - In this paper the analysis of the human acoustic communication channel is presented as a potentially bio-anthropological subject of interest. After a crude survey concerning some important aspects of speech and expressive behaviour a hypothesis is outlined saying that the verbal and the nonverbal content of the speech signal are not just transferred side by side; rather there exist close interconnections between the linguistic and the expressive structures, which is shown regarding the speech melody; the 'cultural' language code makes use of a predominantly 'non-cultural' code of vocalisations for the purpose of linguistic disambiguation and speeding up the communication process. The complementarity of these two codes, their principal independence of each other as well as their different cerebral representation contribute to the high efficiency of speech as a communication tool. PMID- 1859203 TI - Influence of trifluoperazine on the late stage of influenza virus infection in MDCK cells. AB - We investigated the influence of the anticalmodulin drug, trifluoperazine (TFP) on influenza virus growth in MDCK cells. The inhibitory effect of TFP on virus growth was observed even when TFP was added at a late stage of infection. This inhibitory effect was concentration-dependent in the concentration range of 20-35 microM. At 35 microM, TFP caused a complete alteration in the distribution pattern of hemagglutinin (HA), concomitant with a decrease in the appearance of HA on the cell surface. After removal of the drug, the HA gradually began to show a normal distribution pattern and reappeared on the cell surface. The time course of rearrangement of HA was in accord with that of the recovery of cell supernatant infectivity. Scanning electron microscopic study revealed that the drug did not cause accumulation of the progeny viruses on the cell surface. The drug effect on the virus growth was reversed by the simultaneous presence of purified calmodulin (CaM). These data suggest that TFP acts as a reversible inhibitor of influenza virus morphogenesis, but not budding, by disturbing cellular CaM and/or CaM-dependent functions. PMID- 1859202 TI - Inhibition of proliferation of human immunodeficiency virus type 1 by novel heteropolyoxotungstates in vitro. AB - Fifteen heteropolyoxotungstates were tested for their effects on the proliferation of human immunodeficiency virus type 1 (HIV-1) using an in vitro system consisting of MT-4 cells and HTLV-IIIb. Eight heteropolyoxotungstates (HPOTs) with the Keggin structure or dimerized deficient Keggin structure proved to be potent inhibitors of HIV-1. In contrast, seven non-Keggin HPOTs including HPA 23 did not have significant effects on HIV-1 proliferation at non-toxic doses. [PTi2W10O40]7- (PM-19) was the most potent inhibitor of HIV-1 among the 15 HPOTs tested. The inhibition of HIV-1 replication by PM-19 presumably results from impaired virus adsorption and/or penetration into target cells. Viral spread of HIV-1 and HIV-2 on cell-to-cell basis was also susceptible to PM-19. In combination, PM-19 and 3'-azido-3'-deoxythymidine were synergistic in inhibiting HIV-1 proliferation. PMID- 1859205 TI - Tributyltin antifoulings: a threat to the Hong Kong marine environment. AB - Tributyltin (TBT), the active ingredient in antifouling paint, has demonstrated extreme potency but also high toxicity to non-target marine organisms; it bioaccumulates in the food chain, and research evidence of its damaging effect on the reproduction and growth of various marine life forms have prompted action by various countries to regulate or ban its use in antifouling products. The Hong Kong Environmental Protection Department has embarked on a monitoring programme, and TBT has been detected in polluted clam samples, as well as water and sediment samples in certain marinas, typhoon shelters, and mariculture sites. This paper reports some of the findings to date. PMID- 1859204 TI - Toxic effects of long-term intratracheal administration of vanadium pentoxide in rats. AB - The toxic effects of vanadium pentoxide were investigated following chronic exposure. Rats were exposed intratracheally once a month (0.56 mg V2O5/kg) for 12 months. Body weight gain of exposed animals slowed down following the 10th treatment when compared to the corresponding controls. Lung weights were significantly greater than controls; however, other organ weights were not changed. Blood glucose of treated animals was slightly decreased whereas blood total cholesterol was reduced markedly. The in vitro experiments were performed to explain the mechanism of chronic toxic effects. The results of these experiments confirmed that vanadium(V) undergoes one-electron redox cycling in rat lung biomembranes and that reoxidation of vanadium(IV) initiates lipid peroxidation under aerobic conditions. The lung is the primary target organ during the intratracheal exposure to V2O5. It is postulated that free-radical redox cycling of vanadium may be responsible for the observed pulmonary toxicity. PMID- 1859206 TI - Acute toxicity of permethrin to four size classes of red swamp crayfish (Procambarus clarkii) and observations of post-exposure effects. AB - The mean static acute 96-h LC50 of permethrin [(3-phenoxybenzyl (+) cis, trans, 3 (2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate)] to red swamp crayfish (Procambarus clarkii) 8-12 mm (0.017 g), 25-35 mm (0.64 g), 45-55 mm (2.45 g), and 65-75 mm total length (8.98 g) was 0.44, 0.85, 1.30, and 0.81 micrograms/L, respectively. Permethrin toxicity did not differ among immature or mature male and female P. clarkii. Crayfish surviving permethrin exposures exhibited no differences in post-exposure growth, survival, onset of sexual maturity, or the reproduction of viable young when compared to non-exposed controls. Teratogenesis was not observed in third-instar crayfish produced from permethrin-exposed parents. PMID- 1859208 TI - 2,3,7,8 Tetrachlorodibenzodioxin in fish from the Pigeon River of eastern Tennessee, USA: its toxicity and mutagenicity as revealed by the Ames Salmonella assay. AB - Levels of 2,3,7,8 tetrachlorodibenzodioxin (TCDD) were determined in both striated muscle (fillets) and whole body extracts of fish specimens harvested during a two-year period (1987-1989) from the Pigeon River (between Hartford and Newport) of Eastern Tennessee (USA). Whole body (wet weight) fish extract levels as high as 117 micrograms/kg body weight and composite fish fillet (wet weight) extract levels as high as 87 micrograms/kg fillet weight were observed. Pure TCDD was found to be highly toxic to the Salmonella typhimurium strains TA97, TA98, and TA100 at dosages which exceeded 825 ng TCDD/ml in the top agar of the Ames Salmonella assay. An 825 ng/ml TCDD dosage was not mutagenic to any of the tested Salmonella strains, either with or without metabolic activation (S9 mix). However, when acidic fish extracts from the Pigeon River were tested for mutagenicity, most of the fish extracts were mutagenic to Salmonella strains TA97, TA98, and TA100. These mutagenic extracts also demonstrated mutagenic dose response curves. Other chemicals within the extracts as well as synergistic effects may account for the mutagenicity. PMID- 1859207 TI - The possible role of phospholipase A2 in hepatic microsomal lipid peroxidation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. AB - The induction of lipid peroxidation in hepatic microsomes of rodents treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is well documented. The potential mechanisms involved in TCDD-induced microsomal lipid peroxidation were investigated, using selected inhibitors and free radical scavengers in vitro. Rats were treated with 40 micrograms TCDD/kg orally as a single dose. Inhibitors of phospholipase A2, including a variety of phenothiazines, dibucaine, imipramine, and verapamil, inhibited in vitro microsomal lipid peroxidation in response to TCDD administration. In addition, the lipoxygenase inhibitor quercetin, and the hydrogen peroxide scavenger aminopyrine inhibited lipid peroxidation with microsomes from TCDD-treated rats. The singlet oxygen scavenger beta-carotene, the cytochrome P-450 substrate benzphetamine, and the cyclooxygenase inhibitor indomethacin produced moderate enhancement of hepatic microsomal lipid peroxidation. The results suggest that activation of phospholipase A2 may play a critical role in the metabolic events associated with hepatotoxicity and ultimate cell death produced by TCDD. The results also support the involvement of hydrogen peroxide in TCDD-induced microsomal lipid peroxidation. PMID- 1859209 TI - Effect of beta-cyclodextrin on mucochloric acid and 3-chloro-4-(dichloromethyl)-5 hydroxy-2(5H)-furanone. AB - Cyclodextrins form inclusion complexes with a wide range of guest molecules which wholly, or in part, fit into their hydrophobic cavity. Since no covalent bonds are formed in this complexation, the guests can subsequently be eluted. The possibility of such complexation was envisioned as a means of removing chlorinated furanones from drinking water. Using a combination of infrared and ultraviolet techniques, evidence is presented for inclusion complex formation between mucochloric acid and beta-cyclodextrin in acidic aqueous solutions. Ultraviolet evidence supports the conclusion that under these acidic conditions, mucochloric acid exists in its cyclic form. Solid samples of the mucochloric acid beta-cyclodextrin complex could be isolated by recrystalization of a 1:1 mole ratio of the above compounds from water at pH approximately 2. Solid sample infrared (potassium bromide or Nujol) showed a carbonyl shift of approximately 20 cm-1 when mucochloric acid was compared to the mucochloric acid-beta-cyclodextrin complex. No such shift was found upon simply grinding together the above components. Thus the carbonyl shift is ascribed to inclusion complexation of mucochloric acid into the beta-cyclodextrin cavity. Melting point and thin-layer chromatographic analyses also yielded supporting evidence for the formation of solid mucochloric acid-beta-cyclodextrin complexes. Pilot studies with 3-chloro-4 (dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), suggest a similar beta cyclodextrin-complex formation in acidic solutions. PMID- 1859210 TI - Oxidant, mixed-function oxidase and peroxisomal responses in channel catfish exposed to a bleached kraft mill effluent. AB - Channel catfish (Ictalarus punctatus) were exposed to 0, 10, 20, and 40% bleached kraft pulp and paper mill effluent (BKME) for up to two weeks. Fish were sacrificed on days 1, 3, 7, and 14 of exposure. Blood, liver, and gill tissues were assayed for biochemical responses associated with oxidative stress (superoxide dismutase, catalase, and glutathione peroxidase activities and methemoglobin, reduced glutathione, and malondialdehyde concentrations), peroxisome proliferation (palmitoyl-CoA oxidase and lauroyl-CoA oxidase activities) and the mixed-function oxidase system (cytochrome P-450 difference spectra and ethoxyresorufin O-deethylase activities). There were significant dose related increases in hepatic catalase and ethoxyresorufin O-deethylase activities and significant decreases in hepatic reduced glutathione concentrations. There were also significant increases in lauroyl-CoA oxidase and palmitoyl-CoA oxidases activities, both components of the fatty acid beta-oxidation system and located in peroxisomes. No statistically significant changes were seen in the other components studied. The increases in catalase and the fatty-acid oxidase activities suggest that BKME exposure may have resulted in peroxisome proliferation in catfish hepatic tissue. PMID- 1859212 TI - The mechanism of pesticide transmission through apparel fabrics: a comparison of drop and spray exposure methodologies. AB - The effect of exposure methods on pesticide solution transmission and mechanism was examined for three fabrics. Drop and spray methods of exposure were used. The drop method of exposure resulted in significantly higher amounts of pesticide transmission than did the spray method. Using the drop method, a lower proportion of the particles remained in the top of the test fabric indicating much had transmitted into or through the fabric. The large droplet mass and increased volume per unit area produced during drop exposure resulted in a combination of increased force and saturation, enhancing the movement of the particle through the fabric. Fabric characteristics of construction and fiber content also influenced the transmission mechanism and quantity. The twill fabric was a better barrier to transmission than the plain fabrics. The cotton fabrics prevented transmission better than the cotton/polyester fabric. PMID- 1859211 TI - A rapid lead test: public outreach and testing to detect leachable lead in ceramic ware. AB - A modification of the U.S. Food and Drug Administration (FDA) lead screening test of ceramic ware was made to screen large numbers of samples in a short time frame. Ceramic ware in use by Davis and Sacramento, California residents was tested. Lead was leached from ceramic ware with citric acid and identified by rhodizonic acid in this quick, qualitative test. Of 92 individual pieces of pottery tested, approximately 6.6% were positive for leachable lead. Approximately 67% of the positive samples were handmade in Mexico. This rapid test is sensitive to two (2) parts per million (ppm, microgram/g) leachable lead. Ceramic ware with detectable leachable lead levels may present a health risk to individuals who habitually use such items for food storage and/or consumption. Because only 20-30 minutes is needed to perform the test, immediate communication of results to the participant is possible. PMID- 1859213 TI - [Identification of dog bites using a comparative video analysis]. AB - Pictures from wounds are identified as bite marks of dogs with help of the video comparison-technic. It is shown, that two dogs had left bite marks. PMID- 1859215 TI - [Unusual wound morphology after textile penetration by the automatic rifle (StG) 58. A case report]. AB - Technical characteristics of the used fire-arm and ammunition, the firing range and the shot through garments of the victim are essential factors, that exercise an influence on the appearance of gunshot injuries. An exemplary case-report shall emphasize the importance of these factors. It deals with a suicidal double shot fired from an automatic rifle by a young soldier. The wounds were localized in the left chest region and the adjacent skin was blackened by soot in a remarkable geometrical pattern, although an ammunition with a smokeless charge has been used. By means of comparative shots we have good reasons to suppose this phenomenon to be caused by rests of gun powder and pressure of the explosion gas leaved in the barrel after the first shot. The second projectile pushed out this explosion gas to the skin that had been uncovered in a star-shaped way by the first shot. PMID- 1859217 TI - [Practical value of LDH-X determination for the detection of sperm traces]. AB - The examination of 38 stains collected in sexual offences provided spermatozoa positive, LDH-X-negative results in 4 samples and spermatozoa-negative, LDH-X positive results in 6 samples. The results suggest that besides the microscopic detection of spermatozoa the demonstration of LDH-X should be performed in medicolegal identification of seminal stains. PMID- 1859214 TI - [Death caused by sharp injury. Criminologic and criminalistic aspects]. AB - From 3497 obductions during the ten years between 1979 and 1988 100 homicides and 18 suicides were caused by sharp trauma. Homicide by sharp trauma is the most frequent method for killing. These 100 homicides were analysed in relation to the age and nationality of victims and perpetrators, place of action, number and localisation of wounds, cause of death. The main results are discussed, particularly those which vary from the results of other authors. PMID- 1859216 TI - [Group-specific component imaging from trace material using isoelectric focussing and electroblotting]. AB - GC-subtyping was carried out on blood stains, that had been made on glass and stored under room temperature-conditions. Using isoelectric focusing in polyacrylamide gel, followed by transfer to nitrocellulose membrane by semi-dry electroblotting and detection with enzyme-linked antibody complex the GC detection was possible even after 64 days. Methodical problems are discussed. PMID- 1859218 TI - [Morphology of Kronlein cranial gunshot exemplified by a suicide with a model cannon]. PMID- 1859219 TI - [Holderlin: review of pathographic analysis]. AB - The life and work of Holderlin confront the psychiatrist with the age-old problem of the relationship between artistic creation and mental illness. This theme has inspired multitud of writings, many of which fail to stand up to serious analysis. Although in the last century interest centred on the literary value of his work, more recently various authors have approached his life and work from a psychopathological standpoint, generally choosing one of two perspectives. The first tries to find the schizophrenic aspects of his poetry, and how it changed after the illness appeared. The other tries to find biographical clues which could throw some light on the development of his psychosis or, at least, on his reactions to its progression. The following study review several works which focus on the poet's illness, by authors ranging from Jaspers to Jung, Laplanche, Peters and others. PMID- 1859220 TI - [Schizophrenia and panic attacks]. AB - The coexistence of schizophrenia and panic attacks has been reported several times in the literature on this topic. In this paper two new clinical cases of this association have been exposed. Also, diagnostic and therapeutic implications have been debated. The literature related to this topic is reviewed. PMID- 1859221 TI - [Auditory hallucinations in bilingual subjects]. AB - The relationship between bilingualism and psychopathology has received scant attention is psychiatric literature. We present four psychotic patients whose mother language which they usually spoke, was basque, whereas the psychopathological auditory phenomena took place in spanish. PMID- 1859222 TI - [Isolated sleep paralysis in patients with disorders due to anxiety crisis]. AB - The relationship between isolated sleep paralysis and panic disorder in adults is analyzed in this study. The patients included in this work presented anxiety disorder with agoraphobia and were compared with a group of normal controls. The percentage of patients with sleep paralysis was 40% significantly higher than those encountered in the control group (20%). The existence of this syndrome do not seem to modify the clinical manifestation or severity of panic disorder. PMID- 1859223 TI - [Secondary effects of lithium. Their evaluation]. AB - A groupe of 52 patients in long-term lithium treatment were questioned about side effects. The K. Ghose questionnaire was used which contained 36 items. The most frequent complaints were hand-tremor, dry mouth, poor memory, polyuria, diarrhoea, weight gain. We hypothesize that apart from symptoms clearly demonstrated to be caused by lithium treatment (polyuria, hand-tremor, weight gain diarrhoea). Other complaints such as dry mouth, poor memory or skin eruptions occur frequently and they are also related to lithium. PMID- 1859224 TI - [Neuropsychiatric aspects of HIV infection]. AB - The results of a study about psychiatric morbility in patients suffering from HIV infection treated in a psychiatric consulting department of a general hospital are presented. Out of one hundred of individuals studied, 93 showed a diagnosis in Axle I according to DSM-IIIR criteria for mental disorders classification. The diagnosis most frequently found was the one of disorders due to drugs dependence, in 41%; organic mental disorder in 29%; adaptation disorders in 15% and affective one in 5% of cases. In sixteen patients of the sample a follow-up was carried out finding ad evolution towards dementia. Diagnostic difficulties of this population and usefulness of carrying out a revision of diagnostic classifications usually employed are debated. PMID- 1859225 TI - [Dystonia in the painting of Matias Grunewald . Epidemic ergotism in the late middle ages]. AB - Mathias Grunewald painted in the Rhin vallee at the time of Albert Durer and Lucas Cranach. In the first part of the XVI Century he painted for the antonin friars at Issenheim, place devoted to the care of patients with "St Anthony's fire" or chronic ergotism. He despicted figures with abnormal postures simulating focal and generalized dystonia. It is likely that patients with chronic ergotism modelled for Grunewald and that his paintings are the first artistic representation of dystonia. PMID- 1859226 TI - [Family studies in the fragile X syndrome]. AB - A family study and detection of bearer individuals has been carried out in five families suffering from the fragile X syndrome by means of clinical and cytogenetical examination, as well as by DNA recombination techniques in one of them. In 14 males the X marker chromosome was found. In 45 females studied in order to find bearer features, 23 heterozygote individuals have been detected. Out of those 23 cases, 11 were fragile X positive and in the remaining 22 a previous risk of 25-50% was estimated. In this group we used the Bayes theorem considering as conditional probabilities to bear a healthy male and to be fragile negative and the risk of being a bearer person decreased in all the cases. The significance and difficulties of the genetical prevention in families suffering from this syndrome because of the great number of young female with risk at the reproductive age are debated. The DNA study with the St14 sound (DXS52 Locus) in a family was concordant with the cytogenetical studies. A possible recombination in an individual suffering from fixation, atypical phenotype and low percentage of the maker expression. PMID- 1859227 TI - [Short-term effects of the isolated platform on corticosterone plasma level]. AB - Plasma corticosterone was measured, in rats, after a 30 min, treatment either on small platforms used to induce paradoxical sleep deprivation, on large platforms utilized as control or in home cages ("Dry Control"group). The subjects on both platforms showed similar plasma corticosterone levels, those levels being significantly higher than the ones shown by "Dry Controls". It is concluded that the use of large platforms as control of the stress induced by the small platforms in those experiments aimed at determinating the relationship between short-term post-training paradoxical sleep deprivation and memory consolidation allow to discriminate the specifical effects induced by paradoxical sleep deprivation from the putative modulatory effects of learning exerted by the stress induced by the method. PMID- 1859228 TI - [Subcellular distribution of soluble and membrane-bound aminopeptidase in the left and right hemispheres of young and adult rats]. AB - The levels of soluble and membrane-bound aminopeptidase activities were assayed in subcellular fractions from young (1 month old) and adult (5 month old) left and right rat brains, using Leu-, Arg- and Asp-2-naphthylamide as substrates. Both soluble Leu- and Arg-aminopeptidase activities showed the highest levels in the synaptosomal fraction in the two groups of rats. The highest levels of membrane-bound Leu- and Arg-aminopeptidase activities were found in the microsomal fraction of the two ages studied. There were no differences between the two ages in soluble Leu- and Arg- aminopeptidase activities. However, a significant decrease in both membrane-bound activities was evidenced in the synaptosomal fraction of adult rats. The young rats showed the highest soluble and membrane-bound levels of Asp-aminopeptidase activity in the microsomal fraction but no differences among fractions were found at 5 months of age. The soluble Asp-aminopeptidase activity of the homogenate and the mitochondrial fraction was significantly increased in adult animals when compared to that of younger ones. Finally, no differences between left and right brains, in soluble or membrane-bound activities, were found neither in young animals nor in the adult ones. PMID- 1859229 TI - [Tropical pediatrics: necessary exchanges]. PMID- 1859230 TI - [Organ transplantation in children. Which donors? At what cost?]. PMID- 1859231 TI - [Children with short stature]. PMID- 1859232 TI - [Neonatal septicemias: biological diagnosis and antibiotherapy. Apropos of a series of 46 cases]. AB - The records of 46 neonates with proven septicaemia were retrospectively studied. Patients could be divided in 2 groups: in group 1 (21 infants) a positive blood culture was obtained before one day of life; in group 2 (25 infants) a positive blood culture was obtained between days 1 and 28. The sensitivity of 9 chemical and bacteriological tests and the efficacy of the initial antibiotic treatment were examined in both groups. Of the 21 germs isolated in patients from group 1, 86% were Gram positive bacteria and 95% were susceptible to ampicillin. Of the 26 germs isolated in patients from group 2, 80% were Gram negative enteric bacteria and 86% were susceptible to cefotaxime. Bacterial tests (gastric aspiration, antigen detection, feces culture) had a better sensibility than biochemical tests (C reactive protein, orosomucoid, fibrinogen). PMID- 1859234 TI - [Compliance in adolescents with chronic disease]. AB - This study was undertaken with the aim of improving the understanding of the phenomenon of compliance in adolescents presenting with chronic diseases. In 192 subjects aged 12 to 20 years presenting with diabetes, asthma, cystic fibrosis, systemic lupus erythematosus or juvenile rheumatoid arthritis, appointment keeping, compliance with prescribed medical regimens or general instructions and the filling up of a calendar describing the daily levels of fatigue were studied. Correlations (Pearson) between these various types of measurements were weak: from 0.04 to 0.26. Appointment keeping was about 90%. Overall compliance either with treatments or with general instructions was 50% only (without clearcut changes according to diseases); however only 11% of subjects presented with a good compliance with all the treatment components. Various factors (familial environment, perception of the disease and of the patient-physician relationships) were significantly associated with compliance (p less than 0.005). These results emphasize the necessity of taking care of all aspects of compliance, which is difficult to predict at this age, due to the multiple factors involved. PMID- 1859233 TI - [Infants born to kidney transplant recipients]. AB - Over a period of 24 years, 23 women who had undergone renal transplantation gave birth to 26 children whose gestational ages were above 28 weeks. The average duration of stable kidney function tests before the onset of pregnancy was 34.5 months (6 to 109 months). Immunosuppressive treatment consisted mostly of azathioprine and steroids (20/26), steroids and cyclosporin A (CyA) in one case, and azathioprine, steroids and CyA in 5 cases. Average gestational age at birth was 35.2 weeks (30-40 weeks), average birth weight was 2,330 g (1,160-3,700 g). Caesarean section was performed in 73% of cases. The most frequent neonatal pathological condition was the occurrence of respiratory distress, most often related to prematurity and the mode of delivery. No child presented with any lethal congenital malformation. Children born to mothers who were given CyA did not present with more congenital malformations or renal function impairment. PMID- 1859235 TI - [Pharmacokinetics of aspirin in African children with normal nutrition and malnutrition]. AB - Pharmacokinetics of aspirin given orally at antipyretic dose (12 mg/kg) were studied in 11 African children aged 4-48 months. In order to examine the influence of nutritional status on aspirin kinetics, children were classified according to Waterlow criteria. Blood samples were collected during the 8 hours following the initial dose. Albumin, prealbumin and transferrin plasma levels were measured and plasma salicylic acid (SA) concentrations determined by a fluorometric method. Nutritional status seemed to have no prominent effect on plasma concentrations of SA. The volume of distribution found in our study was lower than those obtained in other studies. This could be explained by lower plasma aspirin esterase activities in black children. There were large individual variations in plasma salicylate concentrations. For example, even at antipyretic doses, saturation phenomena appeared in two children. PMID- 1859236 TI - [Anhidrotic ectodermal dysplasia]. AB - The case of an hyperthermia-induced sudden death in an infant with anhidrotic dysplasia is reported. This disease, easily diagnosed, should now be better known and its early assessment, with thermal monitoring might improve the initial severe prognosis. A genetic counselling might be possible. PMID- 1859237 TI - [Neonatal kidney insufficiency and intrauterine exposure to ketoprofen]. AB - An acute kidney failure (AKF) was present at birth in a 28 week-old premature infant exposed in utero to ketoprofen during the last 4 days of pregnancy. Usual causes of AKF were not identified. Thus, AKF might be due to a ketoprofen-induced impairment in renal prostaglandin synthesis. PMID- 1859238 TI - [Transitory acute kidney insufficiency and insulin-dependent after treatment of kala-azar with pentamidine and N-methylglucamine antimony]. AB - Azotemia and diabetes mellitus are now well-known adverse reactions associated with Pentamidine treatment, especially since its prescription in case of Pneumocystis carinii pneumonia. We report the case of a 2 year-old boy, treated for kala-azar with pentamidine and N-methyl glucamine antimoniate who developed adverse effects, characterized by a nephrotic syndrome associated with the classic acute tubular necrosis, and transient diabetes mellitus. PMID- 1859239 TI - [Iconographic rubric. Acute lithiasic pancreatitis, exceptional cause of abdominal pain crisis in sickle cell anemia patient]. PMID- 1859240 TI - [Immune neonatal thrombocytopenia]. PMID- 1859241 TI - [Feeding of young children in the European Economic Community and perspective in 1993]. PMID- 1859242 TI - [Correlations between genotype and phenotype in children with phenylketonuria?]. PMID- 1859244 TI - [Management of abused children]. PMID- 1859243 TI - [Child abuse mistreated]. PMID- 1859245 TI - [Giardiasis and biopsy of small intestine for growth retardation]. PMID- 1859246 TI - [Accelerated desensitization in asthma. 2-year evaluations follow-up of 16 children]. PMID- 1859247 TI - [Cardiotoxicity of intravenous erythromycin lactobionate in the neonatal period]. PMID- 1859248 TI - [49,XXXXY syndrome and congenital cardiopathy]. PMID- 1859249 TI - [Hypertensive action of 5-(beta-aminoethyl)aminoisoxazoles: synthesis and screening of isoxazolopyrazines and isoxazolodiazepines]. AB - The 5-aminoisoxazole 1 is converted via the 4-nitro derivative to the 4,5-diamino compound 4, which cyclises with glyoxal to yield the isoxazolo[4,5-b)pyrazine 5. Decomposition of the isoxazole moiety is always observed in experiments to hydrogenate partially the pyrazine ring and to phenylate the N-atom, respectively. Therefore, the corresponding tetrahydro derivative 6 is prepared from 4 and 1,2-ethandiol ditosylate. Starting with benzohydroxamic acid chloride and a cyanoacetic acid amide the tetrahydro isoxazolo[5,4-e]1,4-diazepinone-4 18 is synthesized. All new compounds are characterized by their spectroscopic data, the reaction mechanisms are discussed. Using the model of the pithed and the anaesthetized rat, resp., the pyrazino- and diazepino-isoxazoles (compounds 5, 6, 13, 18) have less or no hypertensive activity as compared to the corresponding derivatives with fully flexible side chains. PMID- 1859250 TI - Investigations on the antiproliferative effects of amino acid antagonists targeting for aminoacyl-tRNA synthetases. Part III--Combination experiments. AB - The combined effects of amino acid antagonists with proven or potential inhibitory activities on aminoacyl-tRNA synthetases were investigated on the murine leukemic cell line P388 D1. As the best result a summation of the antiproliferative effects was observed. Combinations with established cytostatic agents like platinum complexes or other antitumor compounds also yielded partly additive effects. In experiments performed with asparaginase L-aspartic acid-beta hydroxamate gave synergistic growth inhibition of P388 D1 cells in vitro, which was reflected by additive effects against murine leukemia P388 in vivo. PMID- 1859252 TI - [Antineoplastics 17. Analysis of mono- and disubstituted 2,4-dichloro-5 diethylamino-1,3,5-triazines]. AB - The reactions of 2,4-dichloro-6-diethylamino-1,3,5-triazine (1) with the secondary amines 2a-g lead to the diamino-1,3,5-triazines 3a-e and the melamines 4a and 4b. The structures of the reaction products were established spectroscopically (IR, 1H-NMR, and MS). PMID- 1859251 TI - Induction of drug metabolism can be a homeostatic response. AB - The invasion of the body by toxic agents, in addition to the specific effects, causes a stereotype non-specific response -stress-, and an adaptive phenomenon like drug metabolism. Reserpine or hydrocortisone, causing a typical stress response, produce increased plasma concentrations of corticosterone in rats. Here it is shown that corticosterone administration once, or for three days twice daily (200 mumoles/kg) increase body resistance to zoxazolamine, methyprylon, and tetraethylammonium bromide, reduce their plasma concentrations and augment zoxazolamine, hexobarbital, and aniline in vitro drug metabolism (9000 g liver supernatant). This constitutes a good evidence that drug metabolism can be induced in response to need. PMID- 1859253 TI - [Pharmacokinetics of carboplatin after intraperitoneal administration]. AB - The concentration-profile of the antineoplastic agent carboplatinum in serum and intraperitoneal-fluid (IPF) of six female patients was studied. Pharmacokinetical analysis showed a rapid distribution-phase between both compartments within the first 4h after administration (t1/2 serum = 4.4 h, t1/2 IPF = 3.3 h). Elimination half-life of carboplatinum of 20.3 h from the blood-vessel-system was significantly higher than from the intraperitoneal-compartment (t1/2 = 10.6 h). The relative bioavailability (calculated as AUC-values) was at least 6 times higher for the IPF than for serum within the first 48 h. 98% of measured amount were eliminated from both compartments within this time. The desired high IPF levels support this route of administration. PMID- 1859254 TI - Spectrofluorimetric assay of fluoride ions in pharmaceutical formulations. PMID- 1859255 TI - Applying psychometric criteria to functional assessment in medical rehabilitation: I. Exploring unidimensionality. AB - While rehabilitation providers are facing increasing pressure to document treatment outcomes, critics have warned against the inappropriate use of ordinal functional assessment data in arithmetic operations. Two salient criticisms concern the combination of items representing multidimensional abilities into a single total score, and the indeterminate distances between hierarchical functional assessment scale categories. In this initial study, the factor structure of the Patient Evaluation and Conference System (PECS) was studied to assess the potential for unidimensional measurement. Factor analysis of a multidiagnostic dataset (n = 3,564) yielded eight factors accounting for 60% of the variance among 68 PECS items. The factors indicate that several unidimensional measures may underlie the PECS. These factors are delineated, and further studies of unidimensionality and additivity are recommended. PMID- 1859256 TI - Effects of trunk support and target distance on postural adjustments prior to a rapid reaching task by seated subjects. AB - The purpose of this study was to determine the presence of postural adjustments before a reaching task by seated subjects. Nine seated subjects performed a rapid reaching task to a target placed at shoulder height, 45 degrees to the right of midline. Reach time, timing and magnitude of forces produced by the movement, and onset of deltoid muscle activity were analyzed under supported versus unsupported, and near versus far reach conditions. Reach time was proportional to reach distance. For all reach conditions, initial movement of the center of body mass occurred in a direction toward the target, ie, opposite in direction to reactive forces produced by the accelerating arm. Regardless of support, reactive forces were recorded approximately 30 to 50 msec before arm movement, and represented a greater percentage of body weight, for the far reach conditions. Peak acceleration to the right occurred at proportionately the same time into reach regardless of support or reach distance. Peak acceleration occurred earlier in the supported conditions. This paper provides kinetic evidence of postural adjustments before a rapid reaching task performed by seated subjects. PMID- 1859257 TI - Respiration effect on standing balance. AB - An attempt was made to determine the effect of respiration on standing balance. Ten able-bodied subjects were asked to stand upright on a force platform and were asked to hold their breath after inspiration and after expiration, and to breathe regularly, 4, 6, and 8 respirations per 20 seconds. Sway was measured over 20 second periods with eyes open and eyes closed. The results show that both respiration and eye condition affect the sway distance of the center of pressure on body balance. The sway distance in holding breath after inspiration is significantly greater than in holding breath after expiration, and increasing the respiration rate produces a greater postural sway. Also, the grade of visual compensation for body balance is higher in the regular respiration condition than in breath holding. These findings are applicable for ergonomics, sports, and clinical situations. PMID- 1859258 TI - Leg-length discrepancy: effect on the amplitude of postural sway. AB - The purpose of this study was to investigate whether leg-length discrepancy (LLD) influences a person's standing balance as measured by the amplitude of his/her postural sway. Twenty volunteers between the ages of 20 and 32 participated. Eleven individuals with no measurable LLD constituted the control group. The experimental group consisted of nine individuals with at least a 9.5mm LLD. Each subject stood barefoot on a force platform with their feet together. Center-of pressure data were collected at a rate of 10Hz for 12.8 seconds while the subjects stood with their eyes opened and again with their eyes closed. The amplitude of each person's postural sway in the medial-lateral and anterior posterior directions was calculated from the center-of-pressure data. The results of the study showed that no significant difference existed between the experimental and control groups. There was, however, a significant difference (p less than .05) between the conditions of eyes opened and closed. These results indicate that individuals with an LLD do not have more postural sway than those without an LLD. PMID- 1859259 TI - Treadmill gait retraining following fractured neck-of-femur. AB - The rehabilitation outcome of two methods of gait retraining, was studied in 40 elderly women who had fractured the neck-of-femur. Twenty control subjects received conventional gait retraining, and 20 experimental subjects participated in a treadmill gait retraining program. Rehabilitation outcome was determined by temporal-distance gait parameters and mobility level (house-bound, limited, or unlimited). Muscle strength and range of movement of the lower limb were measured. Previously reported predictors of poor outcome (age, prefracture mobility, admission from sites other than own home, availability of caring person, type of ambulatory aid, presence or absence of senile dementia, and number of concomitant medical diseases) were recorded. Subjects were assessed on admission to the gait retraining program and at discharge from hospital. A 3 x 2 chi-square analysis on discharge mobility level showed the mobility level of the treadmill group to be significantly (p less than .05) higher than the mobility level attained by the control group. Analysis of variance showed no significant differences between the two groups at either assessment time. However, a significant increase in within-group variance from admission to discharge (p less than .01) was noted, and this led to the analysis of a subgroup containing six pairs of subjects matched for number of predictors of poor outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859260 TI - Postural differences between asymptomatic men and women and craniofacial pain patients. AB - A forward head position and rounded shoulders have been implicated in the development or perpetuation of craniomandibular disorders. Since women seek treatment for these problems more frequently than men, postural differences may account for the increased incidence of symptoms in women. The purposes of this study were (1) to compare the sagittal head and shoulder posture of asymptomatic men and women and (2) to compare the posture of asymptomatic and symptomatic women to determine differences in sagittal plane posture. Subjects were 20 asymptomatic men and women volunteers and nine consecutive women patients presenting for evaluation and treatment of craniomandibular pain. The subjects were compared using a valid, reliable, computer-assisted slide digitizing system called the Postural Analysis Digitizing System (PADS). Asymptomatic men and women did not differ in the postural characteristics associated with craniomandibular disorders. Sagittal posture does not appear to be a gender-related factor in these disorders. Symptomatic women, however, do display these postural characteristics to a greater extent than asymptomatic women. Evaluation and treatment of postural dysfunction should be included in the management of these patients. PMID- 1859262 TI - Intermittent pneumatic compression therapy in posttraumatic lower limb edema: computed tomography and clinical measurements. AB - The purpose of our study was to assess the amount of posttraumatic lower limb edema and its distribution between subcutaneous and subfascial compartments before and after intermittent pneumatic compression (IPC) therapy in patients with fractures of the lower leg immobilized with a cast for six to 12 weeks. Computed tomography (CT) was used as an objective method of measuring the compartmental distribution of edema. Sixteen patients with a mean age of 37 years (range 19 to 64 years) were investigated by clinical measurement of the leg circumference and by CT at the ankle joint and at three equidistant (10cm) levels above it. The unaffected leg served as a control for the evaluation of the amount of edema and density of the tissues. Edema was found primarily in subcutaneous tissue. The IPC treatment decreased relative edema from 23% to 15.9% (p less than 0.01) as measured by CT, and from 23.5% to 13.2% as measured clinically. The density of muscle tissue increased 9% (p less than 0.01) and that of subcutaneous tissue decreased 5.6% (p less than 0.05). The IPC treatment influenced both the amount of edema and the density of tissue compartments. PMID- 1859261 TI - External loading comparisons between able-bodied and below-knee-amputee children during walking. AB - The purpose of this investigation was to determine external loading variables that could describe any statistically significant differences between the limbs of below-knee-amputee (BKA) and able-bodied children. Eleven able-bodied children and four BKA children volunteered to participate in this investigation. Force platform data were collected for two consecutive foot falls during two experimental sessions. Significant external load differences existed between the prosthetic limbs and nonprosthetic limbs of BKA children and between limbs of the BKA and able-bodied children. The prosthetic limb generally displayed a subordinate role when compared to nonprosthetic and normal limbs. The nonprosthetic limbs displayed a dominant role when compared to the other limbs. These external loading characteristics of the prosthetic and nonprosthetic limbs may be a logical consequence of the morphologic and functional differences that exist between the groups. It was concluded that as long as the prosthetic limb functions differently from a normal limb, BKA children may have a difficult time walking the same as able-bodied children. It would appear to be advantageous to determine the most appropriate gait pattern for BKA children, given the influence of such factors as prosthetic design, construction, and alignment, rehabilitation, and joint loading. PMID- 1859264 TI - Quantitative cervical flexor strength in healthy subjects and in subjects with mechanical neck pain. AB - Although weakness of anterior cervical muscles is postulated to contribute to persistent neck pain in patients with mechanical neck pain, quantitation of weakness has never been reported. We compared anterior cervical muscle strength in 30 subjects with mechanical neck pain and in 30 asymptomatic control subjects. Testing was performed with the subject supine, chin retracted, and neck flexed. Assessment was made using a hand-held dynamometer with head held at the midline and with rotation left and right within a pain-free range. Analysis with Wilcoxon scores showed that patients with neck pain had significantly less (p less than .05) strength (N.Kg-1) in all three positions than controls (1.16 +/- 0.49 vs 1.71 +/- 0.42, sagittally; 1.01 +/- 0.52 vs 1.47 +/- 0.41, rotation left; .99 +/- 0.46 vs 1.43 +/- 0.43 rotation right; neck pain vs control, respectively.) This weakness and its role in persistent neck pain should be recognized. The efficiency and effect of cervical muscle strengthening in treatment of chronic neck pain should be further defined. PMID- 1859263 TI - Clinical findings associated with pulmonary embolism in a rehabilitation setting. AB - In a rehabilitation setting, pulmonary embolism is a relatively frequent and life threatening complication. Deciding when a patient may be experiencing this condition is difficult, however, because of frequent deficits in patient communication skills (eg, aphasia and cognitive deficits) and the multisystem illnesses affecting many rehabilitation patients. We reviewed the charts of 30 rehabilitation patients transferred emergently during the years 1986 to 1988 with a diagnosis of pulmonary embolism, which was subsequently documented by ventilation-perfusion scanning. The average age of the 30 patients was 65; 63% were women and 20 (67%) had an admitting diagnosis of stroke. The most common new onset clinical findings in the 24 hours before discharge were unusual facial skin color changes (pale, flushed, or cyanotic) (57%), chest or upper back pain (47%), tachycardia (heart rate more than 100 bpm) (40%), hypoxemia (arterial oxygen saturation less than or equal to 90%) (40%), and fever less than 101F (37%). In 63% of the patients, either anxiety, restlessness, diaphoresis, or dyspnea was also noted in the 24 hours before discharge. The data suggest that careful physician and nursing scrutiny may identify clinical signs characteristic of pulmonary embolism, and that the de novo appearance of these constellations of findings may help to select candidates for ventilation-perfusion scanning. PMID- 1859265 TI - Motor variables correlated with the hand-to-mouth maneuver in stroke patients. AB - This study investigated the relationship between each of three independent variables and the completion of the hand-to-mouth maneuver in 23 hemiparetic stroke patients. The independent variables were elbow-extensor muscle tone (graded using the Modified Ashworth Scale); active elbow-flexion range-of-motion deficit measured without the influence of gravity; and elbow-flexion strength measured without the influence of gravity with a hand-held dynamometer. The hand to-mouth maneuver was graded according to the degree of completion using a three level ordinal scale. Spearman (rs) correlations demonstrated a significant relationship between the extent of completion of the hand-to-mouth maneuver and both the active elbow-flexion-range deficit (rs = -.853) and the elbow-flexor muscle force (rs = .829). The correlation of the maneuver with elbow-extensor muscle tone (rs = -.063) was not significant, but the relationship may have been influenced by the fact that only a minority of subjects had elevated tone, and that elevation was minimal. The result suggest that both active-movement deficits and muscle strength may be important to upper extremity function. PMID- 1859266 TI - Characteristics of hospital patients receiving medical rehabilitation: an exploratory outcome comparison. AB - This study classified consecutive hospital admissions to acute medical and surgical wards (n = 3,170) into clinical subgroups based on diagnostic, prognostic, and functional criteria. The groups were (1) independent, (2) terminal, (3) medical, (4) dementia, and (5) rehabilitation candidate. Medical record data from hospital admission, discharge, and nine-month follow-up were collected. The groups had unique patterns of survival, residence, and use of health care services during follow-up. Rehabilitation participants were compared with a group similar in age, major diagnostic category, and functional ability, who did not receive rehabilitation. Only 21% of persons meeting the study criteria for rehabilitation actually received rehabilitation services. At follow up, participants in rehabilitation had lower mortality, spent less time in skilled nursing care, and were less frequently hospitalized. Although exploratory in nature, this study supports previously observed benefits of rehabilitation. In combination with clinical assessment, the process of identifying patient subgroups may be useful in planning interventions more uniformly and in developing measures to reduce selection bias in rehabilitation admission decisions. PMID- 1859267 TI - Hand and wrist strengthening exercises during rehabilitation of a patient with hereditary distal myopathy. AB - The effects of isometric and resistive strengthening exercises on myopathic distal muscles were examined by implementing a program of hand and wrist exercises during the rehabilitation of a patient with adult-onset hereditary distal myopathy. A 78-year-old man with this diagnosis for 18 years entered the hospital after a lumbar laminectomy and complete bedrest for seven weeks. After a three-week course of twice-daily Velcro board, therapeutic putty, and table-side isometric exercises, his hand and wrist manual muscle testing score, hand grasp and pinch strength, and nine-hole peg test times had all improved. In addition, the patient had moved from minimum-moderate assist in dressing and hygiene, and maximum assist in homemaking, to stand-by assist in both areas. The outcome demonstrates the feasibility and functional value of isometric and resistive strengthening exercises in muscles severely affected by a myopathic process. PMID- 1859268 TI - Hereditary coproporphyria: an imitator of multiple sclerosis. AB - Hereditary coproporphyria can cause both peripheral neuropathy and central nervous system abnormalities. There are several similarities between multiple sclerosis and hereditary coproporphyria that are probably due to the central nervous system dysfunction present in both. This report describes a 62-year-old man with a five-year history of progressive paraparesis initially diagnosed as multiple sclerosis. Supporting evidence for the diagnosis of a demyelinating disease included three oligoclonal bands in the patient's cerebral spinal fluid, a prolonged visual evoked response bilaterally, abnormal sensory evoked potentials, and an area of increased signal in the posterior cervical cord suggestive of demyelination that was demonstrated on magnetic resonance imaging (MRI). Features atypical for multiple sclerosis were hypoactive deep-tendon reflexes, electromyographic evidence of peripheral neuropathy, and severe constipation. Elevated urine porphyrins and decreased levels of coproporphyrinogen oxidase confirmed the correct diagnosis of hereditary coproporphyria. The patient improved after being placed on a high-carbohydrate diet. Although central demyelination is known to occur in patients with porphyria, delayed evoked potentials and MRI abnormalities have not been previously reported. PMID- 1859269 TI - [Energy metabolism of growing broiler chickens kept in groups in relation to the environmental temperature. 1. Feed intake, heat production and energy utilization]. AB - In 5 experiments with young broiler chickens kept in groups at environmental temperatures (ET) of 35, 30, 25, 20 and 15 degrees C feed intake, live weight development and heat production were ascertained between their 5th and 57th days of life. Feed intake and live weight were ascertained separately according to sex. With live weight being the same, feed intake increased with decreasing ET. There was no maximum feed intake up to the 57th day of life at between 20 and 25 degrees C. At the end of their 57th day of life the male and the female chickens had achieved the following live weights (in the sequence of decreasing ET 35-15 degrees C): 1342; 2014; 2829; 2946; 2374 and 1367; 1900; 2512; 2496 and 2200 g/animal resp. The highest live weight gain of the chickens was achieved at between 25 and 20 degrees C with 60-70 g/d for male and with 50-60 g/d for female animals. Heat production (HP) increased progressively with age. The highest HP was registered at 20 degrees C ET. PMID- 1859270 TI - [Energy metabolism of growing broiler chickens kept in groups in relation to the environmental temperature. 2. Heat production, thermoregulatory heat production and thermoneutral temperature (short term measurement)]. AB - In 5 experiments the weekly rhythm of the heat production of growing young broiler chickens kept in groups between their 5th and 57th days of life was measured according to the method of short-time measuring (30-minute measuring periods) in dependence on environmental temperature (ET) between 40 and 5 degrees C in stages of 5 K by means of gas exchange and indirect calorimetry. The keeping temperature ranged from one experiment to the other from 35, 30, 25, 20 to 15 degrees C. The dependence of heat production on ET is parabolic in the medium and high ranges of temperature. As a rule, heat production increases progressively with very low ET. Thermoneutral temperature depends on both, the age (live weight) of the chickens and environmental temperature. Thermoregulatory heat production decreases with growing age. It changed from 24 kJ/kg LW0.75.d.K at the beginning to 8 kJ/kg LW0.75.d.K at the end of the experiments. PMID- 1859271 TI - [Energy metabolism of growing broiler chickens kept in groups in relation to the environmental temperature. 3. Moderated model description of the efficiency of the utilization of variable energy for body energy retention]. AB - An attempt is made on the basis of extensive studies on the energy metabolism of growing broilers to describe as a model the efficiency of the energetic utilization of the feed. The following parameters are components of the model: metabolizable energy, energy maintenance requirement, thermoneutral temperature, thermoregulatory heat production, heat production from the partial utilization of metabolizable energy for body energy retention, heat production (total), energy retention, utilization of metabolizable energy (total), live weight, environmental temperature. At environmental temperatures of 35, 30, 25, 20 and 15 degrees C resp. the model statement for the total utilization of metabolizable energy amounts to 32.4, 39.4, 39.6, 37.3 and 36.2% resp. PMID- 1859272 TI - [Effect of flavomycin on the apparent digestibility of crude nutrients in wethers, parameters of rumen fermentation in cattle and feed intake and weight gain of heifers]. AB - Three experiments with five wether each were carried out in order to investigate the influence of various levels of flavomycin (0, 5 and 10 mg per animal and day) on apparent digestibility of artificially dried grass. A short time individual feeding experiment (42 days) with 9 bulls and a long term individual feeding experiment (225 days) with 52 heifers were conducted. Animals consumed 0 or 30 mg flavomycin per day. Parameters of rumen fermentation were investigated. Feed intake and weight gain were measured in the experiment with heifers. Flavomycin did not significantly influence the apparent digestibility of organic matter and crude nutrients as well as parameters of rumen fermentation. Flavomycin did not influence dry matter intake, but increased significantly weight gain (49 g per animal and day, 10.5%) and reduced feed and energy required per kg weight gain (10.6%) in heifers. The reasons of ergotropic effects of flavomycin are mostly unknown at present. PMID- 1859273 TI - [Sexual dimorphism in the response of the large-cell neurons of the rat hypothalamic paraventricular nuclei to water-salt loading and water deprivation]. AB - The responses of large-cell populations of the hypothalamic paraventricular nuclei (PVN) to salt loading and water deprivation in adult male and female rats were studied using morphometric methods at the level of light microscopy. Sexual dimorphism, especially pronounced during functional stress, has been observed in the responses of all large-cell PVN populations. The males proved to be more sensitive. PMID- 1859274 TI - [Cortical-cell thymomas with predominance of so-called nurse-cells in patients with myasthenia]. AB - 30 thymomas in patients with generalized myasthenia studied histologically and immunohistochemically are classified as cortico-cell thymomas (n-15), medullary cell (n-1), mixed-cell (n-10) and cortical-cell thymomas consisting mainly of thymic "nurse"-cells. Pronounced histological features of thymomas with the predominance of "nurse"-cells allow one to consider them as a special variant of thymic tumours. Production of thymic hormones by tumour cells in combination with the loss of HLA-DR antigen expression may be of importance in the pathogenesis of autoimmunization in patients with myasthenia. PMID- 1859275 TI - [Estrogen effect on the development of neurons in an intraocular transplant of rat solitary tract nuclei]. AB - At the light and electron-microscopic levels, using morphometric methods, we investigated the estradiol-17 beta effects on neural growth in the solitary tract nucleus grafts. Estradiol-17 beta increased the functional activity in some neurons of the grafts and caused their cell processes to grow. It also affected the synaptogenesis in the neuropil of the graft tissues. PMID- 1859276 TI - [Combined morphologic criteria in the diagnosis of thyroid diseases]. AB - The use of scanning and translucent electron microscopy, morphometry with the automatic system of analysis in the study of thyroid in patients with nodular euthyroid goiter, diffuse toxic goiter and papillary carcinoma, aged from 27 to 52 years, allowed us to establish the complex of morphologic criteria (qualitative and quantitative) on the cellular and subcellular level, which can be applied for the study of the thyroid under different pathological conditions. PMID- 1859277 TI - [Ultrastructural changes in the adenohypophysis-thyroid system in chronic poisoning by the herbicide linuron]. AB - Ultrastructural adenohypophysis-thyroid system investigation of Wistar male rats under conditions of chronic poisoning by Linuron herbicide and administration of thymohemin immunomodulator was performed. The release of thyrocyte fragments into the vascular lumen, electron-dense deposits in the area of vascular basal membrane, dilatation of endoplasmic reticulum cisternae as well as inhibition of Golgi complex in thyrocytes are observed in the thyroid exposed to Linuron; in the adenohypophysis under the same conditions swelling and splitting of microvessel basal membrane as well as the increase of biosynthetic and secretory thyrotrophic function can be seen. Thymohemin reduces the degree of degenerative processes in the thyroid gland. PMID- 1859279 TI - [Morphofunctional characteristics of the adrenals in patients with cardiovascular pathology]. AB - The adrenals of 65 patients who had died of rheumatism, endocarditis septica lenta, simple chronic bronchitis, atherosclerotic cardiosclerosis and acute trauma were studied histologically, histochemically, morphometrically and using impregnation methods. Processes in the stroma and endocrine tissue were divided into two groups. The first group included changes relating to the manifestation of general adaptation syndrome. The second one deals with changes reflecting the features of the given disease pathogenesis: degenerative and inflammatory processes typical for certain conditions, various states of different adrenal zones. PMID- 1859278 TI - [The endocrine hypothalamus]. AB - Existing data on the peptide hormones in connection with the hypothalamus topography, close interrelationship in the vegetative brain centre of a number of specialized neuronal nuclei with unknown hormonal activity give an example of a highly developed system of the homeostatic function regulation. The author's concept of the neurosecretion mechanism is presented. PMID- 1859280 TI - [Distribution of type I, III, IV, V collagen and fibronectin in the extracellular matrix of malignant schwannomas (immuno-morphologic study)]. AB - The main feature of the malignant schwannoma matrix studied by means of monospecific polyclonal antibodies and method of indirect immunofluorescence is the presence of focally distributed deposits of type IV collagen. Besides this, collagen of types I, III, V and fibronectin are also found. Qualitatively, the extracellular matrix of both benign and malignant schwannoma is similar. The focal localization of type IV collagen is probably associated with areas of the anaplastic lemmocytes proliferation. It is suggested to use the obtained data for the differential diagnosis of malignant schwannoma and fibrosarcoma. PMID- 1859281 TI - [Immunomorphologic study of the extracellular matrix in neurofibroma and benign schwannoma]. AB - The distribution of type I, III, IV and V collagen and fibronectin in schwannomas and neurofibromas showed the similarity in the extracellular matrix structure of both tumours. Both the components of the interstitial connective tissue (collagen of I, III, V types and fibronectin) and component of basal membrane (the IV type collagen) are found in the fibrillar matrix of these two tumours. It is shown for the first time that matrix of rhythmical structures of schwannoma contains the collagen of type IV and fibronectin while the interstitial collagen of types I, III and V is absent. The application of the results obtained for the differential diagnosis of fibrous and neurogenic tumours is discussed. PMID- 1859282 TI - [Morphologic changes in the skin and superficial temporal arteries in Sneddon's syndrome]. AB - Skin biopsies from livedo's areas of 25 patients and fragments of superficial temporal arteries of 10 patients with Sneddon's syndrome were examined. Pathological changes in the dermis arteries of small and medium calibers were found in the form of the intima hyperplasia, proliferation of vascular wall cell elements (80%), arterial thrombosis (with diameter of 60-200 microns). These changes were found in 68% of observations when clinical and morphological signs of vasculitis were lacking. "Arteriopathy" is the most appropriate term for such lesions. Focal and diffuse fibro-muscular elastic hyperplasia of the intima and muscular layer fibrosis in the wall of superficial temporal arteries may be considered as age-associated lesions. Ultrastructurally, a selective damage of the non-adrenergic part of the nervous apparatus of the dermal arteries and superficial temporal arteries were observed; this suggests the participation of the damaged vascular neurogenic regulation in the formation of organic vascular changes. PMID- 1859283 TI - [Knowledge of general pathologic anatomy in 5th-year students]. AB - Students of the 5th year rather well retain their knowledge of the pathologic anatomy obtained during the 3rd year although their mean indices are relatively low. The index of student efficiency may be used for the improvement of teaching and for the student specialization in pathology. PMID- 1859284 TI - [Mesenchymal chondrosarcoma of the radius with metastases in the internal organs]. AB - A rare variant of chondrosarcoma--a mesenchymal chondrosarcoma of the right radiocarpal articulation--is described. The tumour was very small, painless, and did not disturb the joint function but possessed a high mitotic activity and gave lymphogenic metastases to the viscera of the right half of the body. It was not diagnosed clinically. PMID- 1859285 TI - [Primitive trigeminal artery combined with arteriovenous malformation of the brain]. AB - Analysis of the brain circulation and consequences of the intravascular surgery in a woman of 22 with a combined pathology--a primitive trifacial artery with an arteriovenous brain malformation--are presented. The arteriovenous malformation was cured surgically with the use of polystyrene emboli some of which penetrated through the primitive trifacial artery into the branches of carotis interna. The possibilities of the above combinations should be taken into consideration when the method of the intra-vascular surgery is to be chosen. PMID- 1859286 TI - [Xanthogranulomatous pyelonephritis combined with retroperitoneal xanthogranuloma, simulating kidney tumor]. AB - Xanthogranulomatous pyelonephritis is a special variant of interstitial nephritis, when an inflammatory infiltration contains xanthomatous cells. Its diagnosis is difficult and possible only on the basis of a histologic analysis of a surgically removed kidney. A case of xanthogranulomatous pyelonephritis combined with retroperitoneal xanthogranuloma is presented. Kidney carcinoma was suspected and in the course of operation the biopsy of kidney was taken. In the authors' opinion a histologic express diagnosis is recommended during the operation. PMID- 1859287 TI - [Use of a mixture of three types of antibodies for immuno-histologic detection of stomach cancer micrometastases]. AB - The stomach carcinoma micrometastases to lymph nodes were revealed by nondirect immunoperoxidase method. The reaction was performed on the slides of lymph nodes stained with hematoxylin and eosin taken from pathomorphologic archives, by the mixture of polyclonal antibodies to carcinoembryonic antigen, beta-I-meconial antigen and pepsinogen C. The micrometastases were found in 7 of 58 cases (10.8%) that had initial histologic diagnosis "lack of metastases". PMID- 1859289 TI - [Ludvig Aschoff (on the 125th anniversary of his birth date)]. PMID- 1859288 TI - [Use of the immunoperoxidase method at the light microscopic level]. PMID- 1859290 TI - [Functional morphology of peripheral endocrine glands after thymic polypeptide administration in secondary immunodeficiency]. AB - The state of thyroid, adrenal cortex and testicular endocrine cells during the course of thymalin administration was studied. Morphological signs of transitory inhibition of steroidogenic gland function and thyroid stimulation were revealed in rats with intact immune system. Hyperplastic changes in thyroid epithelium were associated with decreased levels of total T3 and T4 and increased serum level of TTH. Regressive changes in the thyroid parenchyma and hyperplasia of steroid-producing elements of the testis and adrenal cortex in the thymectomized guinea pigs could not be corrected by the thymalin administration 45 days after the operation. Our data suggest the search of possible means of control and correction of the patient endocrine status during the administration of immunomodulators. PMID- 1859292 TI - Electrodiagnosis corroborates the neuropathology in the Guillain-Barre syndrome. PMID- 1859291 TI - [Brazilian consensus on the treatment of arterial hypertension. 28-30 September 1990, Sao Paulo]. PMID- 1859293 TI - Natural history and effectiveness of aspirin in asymptomatic patient with cervical bruits. The Asymptomatic Cervical Bruit Study Group. AB - We report a multicenter study in progress involving a prospective follow-up of asymptomatic patients with cervical bruits. The project consists of two components. All patients meeting clinical criteria for eligibility undergo duplex ultrasonography at the time of entry into the study. Those with a carotid stenosis of 50% or greater are enrolled in a randomized placebo-controlled trial of aspirin. All other patients are followed up in a natural history study, also involving biannual clinical and duplex ultrasonographic examinations. Both clinical and anatomic outcomes are assessed. The project consists of a 3-year accrual phase and a 3-year follow-up phase with completion planned for May 1994. Total anticipated enrollment is 588 patients. PMID- 1859294 TI - Predictors of intracranial carotid artery atherosclerosis. Duration of cigarette smoking and hypertension are more powerful than serum lipid levels. AB - The effect of cigarette smoking on intracranial internal carotid artery atherosclerosis (ICAS) was studied by obtaining cigarette smoking histories and data on other potential predictors, including serum lipid estimations, for consecutive patients undergoing carotid arteriography. The duration of cigarette smoking was the most significant independent predictor of the presence of ICAS. Other independently significant predictors of ICAS were hypertension, diabetes mellitus, and current systolic blood pressure. The interaction of diabetes and duration of smoking was a significant negative predictor. In patients for whom serum lipid values were available, lower levels of apolipoprotein A-I were associated with a higher risk of having ICAS. However, the effect of apolipoprotein A-I as a predictor of the presence of ICAS was far outweighted by the effects of duration of smoking and hypertension. PMID- 1859295 TI - Correlative angiographic and pathologic findings in the diagnosis of ulcerated plaques in the carotid artery. AB - We determined the accuracy of angiography in the diagnosis of internal carotid ulcers by comparing the angiographic reports with the pathologic findings in 36 endarterectomy specimens. Eighteen of these specimens had microscopic ulcerations, and the observer with the highest accuracy rate read 12, of which ten were ulcerated. These results revealed a sensitivity of 56%, a specificity of 89%, and an overall accuracy of 61% for angiography. The ulcers were classified into types A, B, and C to assess the interobserver agreement rate among three readers. This resulted in a 4% interobserver agreement among a total of 75 ulcers. Because of the high interobserver disagreement and the poor correlation between angiographic and pathologic findings in the surgical specimens, we conclude that the diagnosis of carotid artery ulceration by angiography is not reliable. PMID- 1859297 TI - Neurosyphilis in human immunodeficiency virus type 1-seropositive individuals. A prospective study. AB - The prevalence of neurosyphilis in human immunodeficiency virus type 1 (HIV-1) seropositive (HIV+) persons was assessed during the course of a study of the neurological complications of HIV-1 infection. One hundred sixty-six asymptomatic HIV+ subjects, 63 neurologically symptomatic HIV+ subjects, and six at-risk HIV-1 seronegative (HIV-) control subjects underwent cerebrospinal fluid (CSF) analysis on entry into this longitudinal study. Three (1.8%) of the asymptomatic HIV+ subjects had both a reactive CSF VDRL test and a reactive CSF fluorescent treponemal antibody-absorption (FTA-ABS) test. Two of these three subjects had a history of appropriately treated early syphilis, and all had a reactive serum rapid plasma reagin test. Of the 63 neurologically symptomatic HIV+ subjects, one patient with dementia had both a reactive CSF VDRL test and a fluorescent treponemal antibody-absorption test. Subjective improvement in cognitive skills followed high-dose, intravenous penicillin therapy. Another subject had a penicillin-responsive myelopathy accompanied by a reactive CSF fluorescent treponemal antibody-absorption test result, but a nonreactive CSF VDRL. Unsuspected neurosyphilis is relatively common in our population of asymptomatic HIV+ subjects and may be responsible for neurological disease in a significant minority of neurologically symptomatic HIV+ persons. Cerebrospinal fluid examination should be performed in all HIV+ persons with a history of syphilis or serological evidence of syphilis, regardless of prior treatment. Additionally, neurosyphilis should be considered in the differential diagnosis of neurological disease in any HIV+ person. PMID- 1859296 TI - Acquired immunodeficiency syndrome. Cerebrospinal fluid findings in patients before and during long-term oral zidovudine therapy. AB - Fifty-two patients with acquired immunodeficiency syndrome were enrolled in this study to evaluate the relationship between cerebrospinal fluid (CSF) zidovudine concentrations and neurologic and human immunodeficiency virus (HIV) culture findings. Paired HIV-CSF culture and neurologic measurements were available in 30 and 45 patients, respectively. Twenty-nine patients were assessable for zidovudine CSF concentrations. Patients underwent lumbar puncture and neurologic testing before and after 8 weeks or more of oral zidovudine therapy (600 to 1500 mg/d). After 8 weeks of therapy, the frequency of HIV isolation from CSF cultures was unchanged. Significant neurologic improvement by examination was noted in 61.5% (32/52) of the patients. The median CSF zidovudine concentration among 29 patients was 0.047 mg/L (range, 0.015 to 0.198 mg/L). No correlation between CSF zidovudine concentration, cumulative dose, or HIV isolation from CSF and persistence or resolution of neurologic symptoms or signs was observed. The mechanisms by which zidovudine improves neurologic function are unclear and appear unrelated to direct clearance of virus from CSF. PMID- 1859298 TI - Expression of 'Alzheimer antigens' in cultured skin fibroblasts. AB - When cultured skin fibroblasts were exposed to culture conditions designed to favor the expression of neuronal antigens, cells from each of 19 patients with Alzheimer's disease reacted immunocytochemically with antibodies to paired helical filaments, Alz-50, or both compared with only a small fraction of cells from 19 identically treated age-matched control cultures. Immunoblots confirmed the presence of soluble material reacting with Alz-50 antibody in the Alzheimer fibroblasts. Ultrastructurally, fascicles of 10-nm filaments were seen that occasionally twisted around each other, but no structures were seen that were identical to paired helical filaments. Thus, cultured skin fibroblasts from patients with Alzheimer's disease developed greater immunocytochemical reactivity with antibodies raised to paired helical filaments than did fibroblasts from control subjects, when cultured under the specified conditions. PMID- 1859299 TI - Alterations in brain monoamine oxidase activity in aging, Alzheimer's disease, and Pick's disease. AB - Alzheimer's disease (AD) and Pick's disease (PD) are dementing disorders of unknown origin. Monoamine oxidase (MAO) is important in the metabolism of a number of monoamine neurotransmitters. This study investigates MAO activity in aging, AD, and PD in frontal and temporal poles, nucleus basalis of Meynert (nbM), and hypothalamus. Regional variations in the activity of the two MAO forms (A and B) were found in aging, AD, and PD. Age-related increase of MAO-B was found in all four areas of the brain, and MAO-A was increased in the nbM and temporal pole. In AD, MAO-B was decreased in the nbM and increased in the temporal pole, while MAO-A was increased in the hypothalamus and frontal pole. In PD, MAO-B was decreased in the nbM and increased in the hypothalamus, while MAO-A was increased in the hypothalamus and decreased in the nbM and temporal pole. These data indicate that with regard to MAO activity, AD and PD are dissimilar diseases and neither strictly follows age-related changes. PMID- 1859300 TI - The short test of mental status. Correlations with standardized psychometric testing. AB - The Short Test of Mental Status can be administered to patients in inpatient and outpatient settings in approximately 5 minutes, and it contains items that test orientation, attention, immediate recall, arithmetic, abstraction, construction, information, and delayed (approximately 3 minutes) recall. The test was administered to a group of demented community patients and their age- and sex matched control subjects. Using an age-adjusted approach, sensitivity of the test to identifying dementia is 86.4, with a specificity of 93.5. The test was compared with standardized tests of cognitive function such as the Wechsler Adult Intelligence Scale, Mattis Dementia Scale, and the Auditory Verbal Learning Test, and showed a high degree of correlation. Group means and standard deviations for subtest items and total score are presented for control subjects (n = 138), demented patients (n = 130), and patients with memory impairment only (n = 20). Percentile scores for subtest items in control subjects are also provided. PMID- 1859301 TI - Epidemiology of myasthenia gravis in Denmark. A longitudinal and comprehensive population survey. AB - The incidence of myasthenia gravis (MG) was found to be constant in calendar time. The mean annual incidence rate was 4.4 per million population. Age- and sex specific incidence rates disclosed a bimodal appearance for both sexes, with a peak age at onset located in the early-onset group and another peak for late onset of MG. Early onset of MG appeared 10 years later for male individuals than for female individuals, whereas the peak for late onset of MG was located at the same age for both sexes. It is suggested that the separation between early onset and late onset of MG should be at the age of 50 years for both sexes, rather than at 35 to 40 years as accepted in most studies. The prevalence of MG has increased in time. On January 1, 1988, the point prevalence rate was 77 per million population (female subjects, 96, and male subjects, 57). This reflects an improvement in prognosis despite the fact that life expectancy was found to be significantly lower for MG patients than that of the sex- and age-matched population. The factors causing increased mortality were found to be operative throughout the duration of the disease. Maximum severity of disease was reached within 2 years from onset in 78% of the cases, and more than 50% of all MG related deaths occurred during the same period. In the course of MG, 70% of all patients experience generalized muscular weakness, and 30% to 40% also suffer from respiratory problems. PMID- 1859302 TI - The pseudotumor syndrome. Disorders of cerebrospinal fluid circulation causing intracranial hypertension without ventriculomegaly. AB - We report a series of eight cases that show a close resemblance to, but are not identical with, pseudotumor cerebri (PTC) as normally defined. The majority of these cases are characterized by raised intracranial pressure without ventriculomegaly. They include two cases of cranial venous outflow obstruction in which clinical or radiologic abnormalities precluded the diagnosis of PTC proper (cases 1 and 2); one case of chronic meningitis in which an abnormal cerebrospinal fluid (CSF) composition precluded the diagnosis of PTC (case 3); two cases without either papilledema or a measured increase of CSF pressure, which in other respects, particularly in response to treatment, resembled PTC (cases 4 and 5); and three cases of what is thought to represent an infantile form of PTC (cases 6 through 8). The purpose of the analysis of these cases is twofold. First, it is argued that these cases throw light on the mechanism of PTC itself, supporting a concept of a disturbance of CSF circulation in this condition, and that they are themselves illuminated by considerations of typical PTC. Second, the cases are used to frame a proposed classification of the pseudotumor syndrome aimed at broadening the diagnostic criteria applied currently to PTC. It is suggested that the pseudotumor syndrome has a single underlying mechanism (disturbed CSF circulation) and that recognition of this mechanism not only clarifies the pathophysiologic processes of PTC but also has important diagnostic and therapeutic implications. PMID- 1859303 TI - The origin of pain in optic neuritis. Determinants of pain in 101 eyes with optic neuritis. AB - In 101 eyes with either anterior or retrobulbar optic neuropathy of ischemic or inflammatory origin, ocular pain occurred significantly more often with retrobulbar optic neuropathy. The association of pain with posterior optic nerve lesions supports Whitnall's hypothesis that the pain of optic nerve inflammation is caused by traction of the origins of the superior and medial recti on the optic nerve sheath at the orbital apex. Eye pain reflected neither severity nor origin of optic neuropathy. PMID- 1859304 TI - Cognitive neuropsychology. Resolving enigmas about Wernicke's aphasia and other higher cortical disorders. AB - Cognitive neuropsychology is a young branch of neuroscience whose ancestral influences include a rich pool of experimental (eg, cognitive, psychology), theoretical (eg, epistemology), and clinical (eg, neurology, neuropsychology) disciplines. An essential principle of cognitive neuropsychology is that disorders of higher cortical functions can be understood in terms of breakdowns of one or more information-processing modules. Each module is the most basic element of intelligence that can be defined based on current knowledge. This approach is a refinement of-not a fundamental departure from-the 19th-century "localizationist" view of language disorders. Wernicke's aphasia, for example, classical attributed to a single cognitive deficit (loss of word sounds), is shown in this review to require damage to multiple distinct information processing modules. Cognitive neuropsychology provides the tools for the type of fine-grained analyses of behavior that are needed to capitalize on recent advances in neuroimaging techniques, including the development of more sophisticated models of brain-behavior relationships. PMID- 1859305 TI - Broca's aphasia following damage to Wernicke's area. For or against traditional aphasiology? AB - Classic aphasiology has been challenged by studies that have employed cranial computed tomography to test predicted anatomic-behavioral correlations. We treated a patient who developed a classic Broca's aphasia but whose computed tomographic scan revealed damage to Wernicke's area, thus seeming to contradict the principles of traditional aphasiology. However, subsequent information obtained by magnetic resonance imaging, intracarotid amobarbital (Amytal) testing, and electrophysiologic studies, including cortical stimulation, demonstrated that the brain-behavior correlations in this patient can be understood in terms of the formulations of traditional aphasiology. PMID- 1859307 TI - Rarer complications of Crohn's (Dalziel's) disease. AB - During the past 30 years, several rarer complications of Crohn's disease have been recognized. Most are life-threatening, and doctors undertaking the management of such patients must be aware of the possibility of such dangerous complications arising. PMID- 1859306 TI - Update on spinal cord paralysis. A preventable injury, a surgical challenge? AB - Spinal cord injuries will not disappear, but the incidence can be reduced. A reduction of up to 50% of spinal cord injury cases is, in the opinion of Menzies' seminar participants, practical and possible but will only occur if the subject is accepted as a major challenge in the surgical world. Great advances in spinal cord injury care were made by surgeons. Prevention is a programme already targeted in other surgical areas. As a multidisciplinary medical and surgical area, spinal cord injury prevention now needs the effective activity of groups of health professionals. Primary prevention must therefore be a target for surgical communities. Surgeons should be among the leaders in the field ensuring good overall management of prevention programmes. PMID- 1859308 TI - Complications following closure of loop ileostomy. AB - The morbidity and mortality of 50 patients undergoing closure of loop ileostomy was reviewed. The patients had a mean age of 57.9 years and significant intercurrent disease. There were no in-hospital deaths or anastomotic leakage at the site of closure. Small bowel obstruction occurred in 12% of patients, all of whom responded to conservative treatment. The wound infection rate was 14%, but the development of a wound infection did not result in a significantly longer hospital stay. We conclude that, when a careful technique of sharp dissection is used, closure of a loop ileostomy is associated with an acceptably low incidence of complications even in elderly and often unwell patients. PMID- 1859309 TI - Medial unicompartment knee replacement. Minimum five year follow-up. AB - Forty-four medial Marmor unicompartment knee arthroplasties were performed at the Hutt Hospital from 1976 to 1983 on 35 patients. Seventy-five per cent were rated as excellent or good, using the Hospital for Special Surgery Knee Rating System. Four arthroplasties were revised at an average of 6 years (range: 2-8), two for late degenerative change in the lateral compartment, one for malposition and one for loosening. There was one late deep infection requiring an arthrodesis at 2 years. It is concluded that medial compartment knee arthroplasty provides satisfactory treatment in the elderly patient, although attention must be directed to technical aspects and patient selection, to afford long-term success. PMID- 1859310 TI - Type IVa choledochal cysts: surgical management and literature review. AB - Type IVa choledochal cysts with cylindrical dilatation of the intrahepatic ducts constitute a relatively less recognized variety of choledochal cysts, and differ from cystic dilatation of intrahepatic ducts in their clinical manifestations and response to treatment. Five patients with type IVa choledochal cysts and cylindrical dilatation of major intrahepatic ducts who underwent cyst excision and Roux-en-Y hepaticojejunostomy are reported. The duration of symptoms was less than 1 year in all patients. Palpable abdominal mass and abdominal pain were present in 3 patients. The traid of jaundice, abdominal pain and mass was present in only 1 patient. The intrahepatic dilatation regressed after excision of the extrahepatic cyst just below the hilum of the liver. The surgical technique is described and the need for excision of the cyst is emphasized. PMID- 1859311 TI - Aurum and Aesculapius: the adventures of Dr Thomas Tate--surgeon, gold seeker, adventurer and teacher. PMID- 1859312 TI - Rhabdomyolysis requiring fasciotomy following heroine abuse. AB - A 29 year old man presented with heroin overdose and rhabdomyolysis necessitating fasciotomy of the left leg muscle compartments. Early recognition of the syndrome of heroine-induced rhabdomyolysis and compartment syndrome is essential to prevent long-term orthopaedic complications. PMID- 1859313 TI - Cutaneous button battery injury: a new paediatric hazard. AB - Button or disc batteries have become increasingly popular as the energy source for electronic devices such as cameras, calculators, computers, watches, hearing aids and children's toys. Button battery burns to the gastrointestinal tract, ear and nose have been reported in children from many centres. Cutaneous injury from these sources has not been similarly reported. We believe our case represents the first, reported to date, to have suffered this injury and highlights this further potential hazard of the small, benign-looking button batteries. PMID- 1859314 TI - Colorectal haemangioma and its relationship to haemorrhoids in childhood. AB - A case of diffuse cavernous haemangioma of the rectum and sigmoid colon is presented to exemplify the propensity for this tumour to be misdiagnosed as haemorrhoids in the paediatric age group. In view of the prolonged morbidity and high mortality associated with this tumour we suggest that, in any child referred for management of haemorrhoids, a diagnosis of colorectal haemangioma be considered. Appropriate investigations include plain abdominopelvic X-rays, sigmoidoscopy and colonoscopy with biopsy, and barium enema. Selective inferior mesenteric angiography and computerized tomography may be helpful. Excision and coloanal sleeve anastomosis is the most favoured operative procedure for this tumour. PMID- 1859315 TI - Galactorrhoea. Report of a case in a male patient. AB - Galactorrhoea is the secretion of milk from the breast in non-physiological circumstances. It is rare in males of any age. We report the case of an adult male who presented with enlarged breasts and tenderness of the left breast, with milky discharge. Bilateral subcutaneous mastectomies were performed. PMID- 1859316 TI - Duodenal necrosis and intramural haematoma complicating acute pancreatitis. AB - Although segmental bowel necrosis is a recognized complication of pancreatitis, the duodenum is rarely involved. We report a unique case of acute duodenal obstruction characterized by transmural necrosis and intramural duodenal haematoma in a young man with acute alcohol-induced pancreatitis. The patient recovered following pancreaticoduodenectomy. PMID- 1859317 TI - Metastatic melanoma of the orbit. A case report. AB - We report a metastatic cutaneous melanoma of the medial rectus muscle of the right orbit which presented with diplopia, exophthalmos and retrobulbar pain. Radioimmunoscintigraphy using melanoma-specific monoclonal antibody was used to confirm the diagnosis and to show the presence of disseminated disease in other areas. Effective palliation was achieved with external beam irradiation. PMID- 1859318 TI - Bechet's colitis: a differential diagnosis in inflammations of the large intestine. AB - A previously well 39 year old woman presented with severe localized and painful anorectal ulceration. There were no other associated symptoms apart from arthritis of the hips and fingers. In the absence of definitive tissue diagnosis, a presumptive diagnosis of Crohn's disease was made. After a period of progression, the inflammation and ulceration subsided with conservative therapy. Following a relatively symptom-free period of 7 years, painful ulceration recurred in the same segment of bowel, which was refractory to steroid therapy but responded to defunctioning of the rectum. Upon excision of the defunctioned rectum, multiple discrete ulcers developed in the remaining colon, with a fistula from the distal sigmoid colon to the midline wound. The patient simultaneously developed painful apthous ulceration of the mouth and throat, and pustules appeared on the perianal skin and trunk for the first time. A colectomy was performed, with good results. The pathology of the colonic lesions is described. The characteristic appearance of these lesions, together with associated 'major' and 'minor' clinical criteria, enabled a diagnosis of Bechet's disease to be made. Although there is some overlap, particularly in the distribution of this condition with Crohn's colitis, the pathologic appearances in Bechet's colitis are relatively distinct. A diagnosis of Bechet's colitis should not be excluded in a patient presenting with atypical inflammatory bowel disease, even if associated clinical criteria are not simultaneously present. PMID- 1859319 TI - Adenocarcinoma arising in a duodenal duplication cyst: a case report. AB - A case of adenocarcinoma complicating a pyloro-duodenal duplication cyst is reported. The diagnosis and therapy are discussed. PMID- 1859320 TI - Central tumour necrosis: a cause for the acute presentation of benign meningiomas. AB - Occasionally, large benign intracranial tumours which have existed for many years present as a relatively acute problem. The mechanisms underlying the sudden change are sometimes unclear but infarction of the benign tumour, subsequent cerebral oedema and an increase in intracranial pressure have been reported. The authors describe such a case of focal infarction in a meningioma with a precise chronology of the clinical, radiological and pathologic findings. PMID- 1859321 TI - Staging abdominal ultrasonography in nasopharyngeal carcinoma. AB - Abdominal ultrasonograms were performed on 81 unselected patients with newly diagnosed nasopharyngeal carcinoma without clinical evidence of distant metastases. Two patients had ultrasonographic features suspicious of, but not diagnostic of, hepatic metastases. One of these two patients developed hepatic metastases six months after the examination while the other was free of metastases at follow-up 33 months afterwards. Of the 79 patients without evidence of metastases on ultrasonogram, two developed hepatic metastases after 22 and 32 months. Based on these results, we do not recommend abdominal ultrasonography as a routine staging investigation for nasopharyngeal carcinoma. PMID- 1859323 TI - Supratentorial tumours. Part I: General role of imaging. PMID- 1859322 TI - Ultrasound guided percutaneous renal biopsy. AB - We performed percutaneous ultrasound guided renal biopsy on 27 patients ages 16 to 76 years. A 14 gauge cutting needle was used. Twenty-six patients had medical renal disease; one patient had a renal mass. Patients were followed by sonograms performed immediately post procedure as well the following day. Serum hemoglobin was obtained prior to the procedure as well as one day post biopsy. Complications included five small hematomas and one transient mild hydronephrosis secondary to blood clots. The hematomas were all first noted on the scan one day post biopsy. We conclude that ultrasound guided percutaneous renal biopsy is a safe procedure which is easily performed by the radiologist. PMID- 1859324 TI - Duplex ultrasound assessment of extra cranial carotid artery disease: its introduction into a radiology department. AB - Duplex Doppler ultrasound (DDU) is a non-invasive and potentially accurate modality for assessing carotid bifurcation disease. It is however technically difficult and an appreciable learning curve has been identified. To assess the accuracy of DDU upon introduction into a radiology department with experienced sonographers and radiologists we reviewed the first twenty-five (25) cases in patients, having both DDU and carotid angiography. Sensitivity of 95% and specificity of 81% were obtained for differentiating greater or less than 50% internal carotid artery diameter stenosis, and in detection of 80% or greater stenosis sensitivity and specificity were 83% and 100% respectively. We conclude that DDU is accurate when introduced into a department already competent in ultrasonography, with results being achieved similar to those reported from more experienced centres. Our results also support the appropriateness of the applied criteria for grading of carotid stenosis. PMID- 1859325 TI - Congestive hepatomegaly--typical features on computed tomography, ultrasound and nuclear medicine. AB - The features of hepatic congestion on computed tomography, ultrasound and nuclear medicine sulphur colloid scans have been reviewed. Hepatic congestion may not be appreciated clinically, especially in the elderly, but the features described should be sufficiently characteristic to establish the diagnosis. The CT appearance may be confused with neoplastic infiltration, so that recognition of the condition may avoid further unnecessary investigations. PMID- 1859326 TI - Carotid and vertebral artery trauma: clinical and angiographic features. AB - Injury to the carotid or vertebral artery is an important clinical entity that requires angiography for definitive diagnosis and evaluation. The common carotid artery may be injured by penetrating trauma while the internal carotid artery is usually damaged by either trivial or blunt trauma. With trivial trauma extracranial internal carotid artery dissection should be considered if there is unilateral headache, Horner's syndrome or delayed transient ischaemic attack, and intracranial dissection if a profound neurological defect occurs immediately following trauma. Injury to the internal carotid artery following blunt trauma includes dissection of the extracranial internal carotid artery, carotid cavernous fistula and pseudoaneurysm formation. These should be considered in a patient with delayed neurological deficit, mandibular or skull fracture, a constellation of orbital signs or diffuse subarachnoid haemorrhage, respectively. Vertebral artery injury is less frequent. Dissection typically follows abrupt cervical rotation and occurs at C1-2, whereas penetrating trauma may involve either the proximal or distal vertebral artery and occlusion, arteriovenous fistula or pseudoaneurysm may be found. Endovascular techniques may be used in either the carotid or vertebral artery to close fistulae or occlude an extensively damaged vessel. PMID- 1859327 TI - Linear atelectasis in the lingula as a diagnostic feature of left lower lobe collapse: Nordenstrom's sign. AB - Collapse of the left lower lobe is sometimes accompanied by linear atelectasis in the lingula. The lingular atelectasis may be more readily apparent than conventional signs of left lower collapse. The mechanism of this association as first described by Nordenstrom is discussed and its value as a diagnostic sign emphasised. PMID- 1859328 TI - A simple prosthesis for ready access to the closed afferent limb of a hepatico jejunostomy. PMID- 1859329 TI - A mattress suitable for use with tilting tables in a radiology department. AB - It has been possible to design a comfortable, yet highly practical mattress for use in general purpose screening rooms with tilt tables. Attention has been paid to materials and fittings and because it is easy for the staff to use it is in constant use. It has become an essential part of our equipment and has considerably improved the comfort of many procedures. PMID- 1859330 TI - Mammographically detected microcalcifications due to pseudoxanthoma elasticum. AB - Mammographic detection and analysis of microcalcification is a key component in the detection of early breast cancer. A casting configuration or granular morphology has a strong association with malignancy. These are relatively easily recognised, but with the proliferation of mammographic screening, other varieties of calcification are being encountered which may pose diagnostic dilemmas. This case report describes the findings in a patient with Pseudoxanthoma Elasticum (PXE) who presented in this way. To our knowledge, this has not previously been documented. Such calcification is not usually visible on conventional radiographs. PMID- 1859331 TI - Antibody to cardiolipin causing hepatic infarction in a post partum patient with systemic lupus erythematosus. AB - This is a case of a thirty one year old post partum patient, with SLE and antibodies to cardiolipin causing hepatic vascular thrombosis leading to infarction. No previous literature account is recorded. PMID- 1859332 TI - Case report--CT findings in adenomyomatosis of the gallbladder. AB - A case report of the CT findings in adenomyomatosis of the gallbladder is presented. Significant CT findings of this entity are variation in wall density, marked differential enhancement of wall layers during dynamic liver scanning and detection of Rokitansky-Aschoff sinuses within the wall. CT apparently depicts both mucosal and muscularis thickening. PMID- 1859333 TI - Sonographic diagnosis of a splenic artery pseudoaneurysm incorporated within an infected pancreatic pseudocyst. AB - In pancreatitis the involvement of adjacent vessels resulting in pseudoaneurysm formation is well known, though quite rare (Gadacz 1978, Kadell & Riley 1967). The diagnosis is usually established on angiography or surgery. We report here a case where the diagnosis of a splenic artery pseudoaneurysm incorporated within an infected pseudocyst, was made sonographically. PMID- 1859334 TI - Polyp masquerading as orbital blowout fracture. PMID- 1859335 TI - Severe reaction to a non-ionic contrast medium. PMID- 1859336 TI - Permanent grounding and flying restrictions in Canadian Forces pilots: a 10-year review. AB - The medical files were reviewed of all Canadian Forces pilots in whom a permanent change in flying category was recommended during the period 1 January 1978 through 31 December 1987. In an average pilot population of 2,697 pilots, 60 permanent groundings (2.2 per thousand) and 209 permanent operational flying restrictions (7.7 per thousand) were assigned among 258 pilots. Coronary heart disease was the most common cause for permanent grounding (25% of total), followed by neurologic disorders including migraine (22% of total), other cardiovascular disorders, including mitral valve prolapse and arrhythmias (17%), and psychiatric problems (12%). Refractive errors were the most common basis for an operational flying restriction (25%), followed by orthopedic disorders (17%), mainly low back pain. The relevance of these observations is discussed in terms of medical selection and surveillance procedures. PMID- 1859337 TI - Personality types among experienced military pilots. AB - Three distinct personality subtypes were empirically identified in a sample of 170 experienced U.S. Army pilots, using a new measure of personality developed for use in occupational settings. The subtypes are similar to those previously derived in a sample of military aviation trainees. No significant differences across the clusters were found for the types of missions flown, years of aviation or military service, or number of flight hours. A significantly greater number of instructor pilots was found among a cluster which comprised the smallest percentage of pilots in the sample. Overall, the results support the notion that no one type of personality is a prerequisite for success in military aeronautics, and highlight the need for additional studies of personality type in military and commercial aviation, using more sophisticated measures of aeronautical adaptability. PMID- 1859338 TI - Scopolamine blood levels following buccal versus ingested tablets. AB - Speed of absorption and elimination of an antimotion sickness drug sets limits on the protection afforded. The aim of this experiment was to determine whether a well proven antimotion sickness drug--scopolamine (hyoscine)--could be absorbed more rapidly from buccal tablets than from the standard issue ingested tablets. Plasma scopolamine levels were measured using a radioreceptor assay of repeated blood samples from 10 volunteers, each of whom took buccal and standard ingested tablets (both 0.6 mg scopolamine hydrobromide) on two different occasions, and from a further 8 volunteers following ingestion of a pharmacy-prepared scopolamine capsule (0.6 mg scopolamine hydrobromide). There was no statistically significant speed advantage for the buccal tablet (mean time to peak levels approx 50 min). Individual variation in the speed of scopolamine absorption and rate of elimination (mean half-life approx 170 min) was great. This may account for failure of motion sickness protection in some individuals. PMID- 1859339 TI - Visually-induced sickness in normal and bilaterally labyrinthine-defective subjects. AB - A group of nine normal subjects (with no overt vestibular dysfunction) and a group of 6 bilaterally labyrinthine-defective subjects were exposed to a visual field rotating about an Earth-horizontal axis (orthogonal to the gravity axis). The visual stimulus was provided by a 3-m diameter sphere with random dots rotating at 30, 45, and 60 degrees per second (degree/s) about the stationary subject's roll, pitch and yaw axes. The subject's head was positioned at the center of the sphere such that it experienced apparent motion in all three axes. Results indicated that in the normal group, symptoms of motion sickness were reported in 21 of 27 test-trials. When labyrinthine-defective subjects were exposed to the roll and pitch stimulus, no sickness symptoms were reported or observed. These results strongly suggest that the vestibular system is necessary for sickness induced by moving visual fields. PMID- 1859340 TI - Effect of extraneous targets on identification of color-coded targets. AB - Subjects matched the color of a vertical target line, presented in 1 of 10 colors, to a set of 10 colors. The target line was presented either in isolation or together with 5 additional colored lines. Neither mean reaction time nor the number of matching errors increased when the extraneous lines were present, and the types of color confusions did not change systematically. PMID- 1859341 TI - Importance of eccentric actions in performance adaptations to resistance training. AB - The inability of the exercises presently used during space-flight to maintain muscle strength and mass may reflect the absence of eccentric (ecc) muscle actions. This study examined the importance of ecc actions in performance adaptations to resistance training. Middle-aged males performed 4-5 sets of 6-12 repetitions (rep) per set of the leg press and leg extension exercises 2 d each week for 19 weeks. Group CON/ECC (n = 9) performed each rep with concentric (con) and ecc actions, group CON (n = 8) with only con actions. Group CON/CON (n = 10) performed twice as many sets with only con actions. The resistance per set was selected to induce failure within the prescribed number of rep. Eight subjects did not train and served as controls. The increase in the three rep maximum (3RM) after training, in general, showed a hierarchy such that CON/ECC greater than CON/CON greater than CON. The differences (p less than 0.05) were: leg press 3RM with con and ecc actions, CON/ECC greater than CON/CON greater than CON (26 greater than 15 greater than 8%); leg press 3RM with only con actions, CON/ECC or CON/CON greater than CON (22 or 18 greater than 14%); and leg extension 3RM with con and ecc actions, CON/ECC greater than CON (29 greater than 16%). These differences (p less than 0.05) were still evident after 1 month of de-training. The results indicate that omission of ecc actions from resistance training compromises increases in strength, probably because intensity is not optimal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859342 TI - The effect of prolonged intermittent exercise, combined with food deprivation, on plasma metabolite concentration. AB - To examine the effect of continuous fasting combined with prolonged, intermittent exercise on glucose homeostasis, 16 endurance-trained subjects, ranging in age from 18-21 years, were completely deprived of food during 81 h of field maneuvers. Water was supplied to avoid dehydration. Participants marched 10 h each night at an estimated intensity of 35-45% of mean VO2 max covering a total distance of 105 km, and had a relative rest during day time. Blood was sampled prior to the beginning of the march, at the end of 81 h, and after 24 h of recovery. Samples were analyzed for plasma glucose, insulin, alanine, free fatty acids (FFA), and 3-hydroxybutyrate (3-HB). Body weight decreased from a mean (+/- S.E.M.) of 73.0 +/- 0.6 kg at pre-march to 66.5 +/- 0.6 kg at 81 h of fasting (p less than 0.05), and remained unchanged at 24 h after march termination. Glucose, insulin, and alanine decreased, whereas FFA and 3-HB increased significantly at 81 h fast (p less than 0.05). Within 24 h of recovery all parameters changed significantly (p less than 0.05), approaching baseline values. The results indicate that in trained individuals under extreme survival conditions, as in the present study, blood glucose is maintained above hypoglycemic levels at the expense of fat and fat-derived substrates that become the main energy sources utilized. PMID- 1859343 TI - Fluid replacement during sustained activity in the heat: nutrient solution vs. water. AB - This study examined the thermoregulatory and hydrational status of men during sustained activity in a hot-dry (37 degrees C, 20% rh) environment while they consumed only a nutrient solution (nutrient), or consumed only colored, flavored water (control). Eleven heat acclimated young men attempted 24-h sustained activity experiments. These experiments consisted of alternating 45-min bouts of treadmill walking (410 W, approximately 30% VO2max) and rest (including sedentary activity). Data were analyzed through 13 h (after 13 h subjects began to discontinue testing). No significant differences between trials were observed for metabolic rate, fluid intake, skin or rectal temperature, sweating rate, plasma volume (as indicated by hemoglobin concentration) or plasma glucose concentrations. By the 8th h plasma osmolality was higher and by the 11th h plasma free fatty acids were lower during the nutrient trial compared to the control. In separate experiments with nine different men, the gastric emptying rates of the nutrient solution and water were compared during exercise (55% VO2max) in the heat (35 degrees C, 20% rh). The gastric emptying rates of the nutrient solution and water were similar (approximately 20 ml.min-1). These data indicate that during 13 h of sustained activity in a hot environment, the nutrient solution and water provided similar thermoregulatory and hydrational benefits. PMID- 1859344 TI - The durability of hydrogel extended-wear contact lenses worn for daily wear by USAF aircrew members. AB - Hydrogel extended-wear contact lenses, worn on a daily-wear regimen, were tested for 1 year by USAF aircrew members. A total of 62 eyes were fitted with Hydrocurve II (55% water content) spherical lenses, 29 with Hydrocurve II (55% water content) toric lenses, and 61 with CSI-T (38.5% water content) spherical lenses. The mean lens replacement rate for torn lenses per aircrew member was determined to be 1.45 lenses a year. The replacement rate of Hydrocurve II spherical lenses compared to CSI-T lenses was not statistically significant. However, the replacement rate for Hydrocurve II toric lenses was significantly lower than both Hydrocurve II spherical lenses and CSI-T lenses (p less than 0.01). The extended-wear lenses tested in this study appeared to be durable enough for the rigors of daily wear. PMID- 1859345 TI - Transcranial Doppler evaluation of syncope: an application in aerospace physiology. AB - A non-invasive method which combines the simultaneous measurement of mean arterial blood pressure (MBP), heart rate (HR) and mean cerebral blood flow velocity (MFV) was used to monitor patients with history of syncope, in horizontal and vertical posture tilt at 80 degrees. MFV in the right middle cerebral artery was measured using a transcranial Doppler instrument (TCD). MFV decreased concurrently with the onset of symptoms, and at the time of syncope reached an average of 68% below pre-tilt values. At the same time MBP showed an average decline of 25%, and HR increased by 38%. There was no correlation between MBP and MFV, at the onset of tilt, presyncope and syncope. MFV, but not HR or MBP, showed significant transition from one condition to the other. These data suggest that there may be a useful application of TCD measurements of MFV in aeromedical evaluation of syncope or syncopal tendency. These measurements would necessarily be used in conjunction with a tilt-table procedure. The possibility exists that MFV might be useful to preclude the actual occurrence of syncope in test subjects, or to show an abnormal tendency toward syncope, but will require more extensive testing than that carried out in the present study. PMID- 1859346 TI - Asymmetric visual deficit at high sustained Gz. AB - Occasionally, acceleration research personnel see an individual who experiences consistent asymmetric visual deficits at high sustained Gz (HSG). Recently, one such centrifuge research subject from this laboratory was investigated with transcranial Doppler sonography. The results indicate an abnormal circle of Willis which could explain the asymmetric visual deficit at HSG. PMID- 1859347 TI - Comments on asymmetric visual loss associated with +Gz-stress. PMID- 1859348 TI - Evaluation of the disposable absorption containment trunk for female U-2 and TR-1 pilots. AB - Female U-2 and TR-1 pilots needed a urine collection device as part of their high flight pressure suit ensembles. The Disposable Absorption Containment Trunk (DACT) had been designed for short term use with the NASA Space Shuttle Program. This study evaluated the DACT for the extended and repetitive use required for integration into the U-2 and TR-1 aircraft. Six female subjects were tested wearing a custom-fit DACT and the 1030 full pressure suit ensemble with torso harness. They were strapped into the U-2 ejection seat with parachute and seat kit for 10 h and 45 min every 3 d for a total of 5 sessions. The DACT was evaluated for absorptive capability and comfort. Subjects were monitored for dermatitis, vaginitis, and urinary tract infections. The DACT reliably absorbed menstrual flow and urinary outputs to 950 cc. Higher urinary outputs resulted in minimal leakage. Dermatitis in the form of mild erythema and chafing was present, but cleared between sessions without medical intervention. Complaints concerning comfort were minor and limited to fit problems. One case of vaginitis developed. There were no cases of urinary tract infection. The DACT was found to be an acceptable method of urine collection for female U-2 and TR-1 pilots. Minor changes in design will enhance the comfort and performance of the DACT. PMID- 1859349 TI - Environmental tobacco smoke (ETS) in airliners--a health hazard evaluation. AB - Some passengers and airline attendants have expressed concern about exposure to environmental tobacco smoke (ETS) in commercial airlines. Irritation of the eyes and respiratory tract, odor, and personal sensitivities are often the bases of complaints. Previous studies demonstrate low concentrations of materials, including ETS. Attendants fly some 800 h per year, passengers much less. Based on previous studies and duration of exposures, the absorbed dose of ETS is less than a cigarette equivalent per year. Nicotine absorption of 0.2 to 0.3 mg in 8-10 h flights has been reported as unlikely to have physiologic effects. The retained 'dose' in relation to the hypotheses of risks to health based on the conflicting results of studies on 'passive smoking' are discussed. There are additional confounding factors in aircraft. We consider segregation into smoking and nonsmoking zones to be reasonably effective in meeting the preferences of passengers. PMID- 1859351 TI - Cases from the aerospace medicine residents' teaching file. Case #44. An aviator with high attitude pulmonary and cerebral edema presenting acute mountain sickness. AB - An aviator with high altitude pulmonary and cerebral edema presenting with Acute Mountain Sickness. The clinical presentation, evaluation and diagnosis of an aviator with acute mountain sickness are discussed. The aeromedical disposition of this patient is also presented. PMID- 1859350 TI - The failure analysis of composite material flight helmets as an aid in aircraft accident investigation. AB - Understanding why a flying helmet fails to maintain its integrity during an accident can contribute to an understanding of the mechanism of injury and even of the accident itself. We performed a post-accident evaluation of failure modes in glass and aramid fibre-reinforced composite helmets. Optical and microscopic (SEM) techniques were employed to identify specific fracture mechanisms. They were correlated with the failure mode. Stress and energy levels were estimated from the damage extent. Damage could be resolved into distinct impact, flexure and compression components. Delamination was identified as a specific mode, dependent upon the matrix material and bonding between the layers. From the energy dissipated in specific fracture mechanisms we calculated the minimum total energy imparted to the helmet-head combination and the major injury vector (MIV) direction and magnitude. The level of protection provided by the helmet can also be estimated. PMID- 1859352 TI - Rational medical standards. PMID- 1859353 TI - Allozyme variation among biotypes of the brown planthopper Nilaparvata lugens in the Philippines. AB - Allozyme variation was studied in three Nilaparvata lugens biotypes infesting specific rice varieties and a biotype infesting a weed grass, Leersia hexandra. Of the 20 enzymes in N. lugens for which activity was noted, 9 were polymorphic. Eleven enzyme loci were monomorphic for the same allele in all biotype populations; the rest were polymorphic for two or more alleles. The mean number of alleles per polymorphic locus was 2.3, while the mean number of alleles per locus was 1.5; heterozygosity ranged from 0.02 to 0.06 (biotype 1 greater than biotype 3 greater than Leersia-infesting biotype greater than biotype 2). Allelic frequency differences were observed in five loci among the four biotypes. However, the coefficient of genetic identity (I) of 0.99+ showed that the four biotype populations were genetically close relatives or merely populations of N. lugens undergoing genetic differentiation. PMID- 1859354 TI - Normal expression of thymidine kinase and O6-methylguanine-DNA methyltransferase in cultured fibroblasts from individuals with hereditary galactokinase deficiency. AB - Expression of the enzymes galactokinase, thymidine kinase, and O6-methylguanine DNA methyltransferase is occasionally coordinately regulated in human cell lines. We have measured the activities of these three enzymes in extracts of fibroblasts from individuals with hereditary galactokinase deficiency. These cells do not express measurable galactokinase activity. The levels of O6-methylguanine-DNA methyltransferase were in the normal range in cells from three galactokinase deficient individuals. The activity of thymidine kinase in the affected cells was in the normal range for two of the three individuals. The reduced thymidine kinase activity in the third individual reflected the extremely poor growth of the cells in culture. Immortalization of one galactokinase-deficient cell line resulted in loss of O6-methylguanine-DNA methyltransferase activity, but the galactokinase and thymidine kinase levels remained unchanged. The data indicate that the loss of galactokinase activity in these individuals is the consequence of an alteration of gene expression which does not involve coordinate silencing with the thymidine kinase and methyltransferase loci. PMID- 1859356 TI - Alpha-type prolamins are encoded by genes on chromosomes 4Ha and 6Ha of Haynaldia villosa Schur (syn. Dasypyrum villosum L.). PMID- 1859355 TI - Aldehyde dehydrogenase (ALDH) isozymes in the gray short-tailed opossum (Monodelphis domestica): tissue and subcellular distribution and biochemical genetics of ALDH3. AB - Polyacrylamide gel isoelectric focusing (PAGE-IEF), cellulose acetate electrophoresis, and histochemical techniques were used to examine the tissue and subcellular distribution, genetics and biochemical properties of aldehyde dehydrogenase (ALDH) isozymes in a didelphid marsupial, the gray short-tail opossum (Monodelphis domestica). At least 14 zones of activity were resolved by PAGE-IEF and divided into five isozyme groups and three ALDH classes, based upon comparisons with properties previously reported for human, baboon, rat, and mouse ALDHs. Opossum liver ALDHs were distributed among cytosol (ALDHs 1 and 5) and large granular (mitochondrial) fractions (ALDHs 2 and 5). Similarly, kidney ALDHs were distributed between the cytosol (ALDH5) and the mitochondrial fractions (ALDHs 2, 4, and 5), whereas a major isozyme (ALDH3), found in high activity in cornea, esophagus, ear pinna, tail, and stomach extracts, was localized predominantly in the cytosol fraction. Phenotypic variants of the latter enzyme were shown to be inherited in a normal Mendelian fashion, with two alleles at a single locus (ALDH3) showing codominant expression. The data provided evidence for genetic identity of corneal, ear pinna, tail, and stomach ALDH3 and supported biochemical evidence from other mammalian species that this enzyme has a dimeric subunit structure. PMID- 1859357 TI - Sequence analysis of heparan sulphate indicates defined location of N-sulphated glucosamine and iduronate 2-sulphate residues proximal to the protein-linkage region. AB - A strategy that we originally used to identify an N-acetylated domain adjacent to the protein-linkage sequence of heparan sulphate proteoglycan (HSPG) [Lyon, Steward, Hampson & Gallagher (1987) Biochem. J. 242, 493-498] has been adapted for analysis of the location of GlcNSO3-HexA and GlcNSO3(+/- 6S)-IdoA(2S) units most proximal to the core protein. [3H]Glucosamine-labelled HSPG from human skin fibroblasts was depolymerized by using HNO2 or heparinase under conditions that allowed cleavage of all susceptible linkages. The degraded PG was coupled to Sepharose beads through the protein component, enabling specific recovery of protein-linked resistant oligosaccharides. These were released by treatment with alkaline borohydride and analysed by gel filtration and gradient PAGE. This strategy allowed investigation of the sequence of sugar residues along the chain relative to a common reference point (i.e. the reducing end of the chain). HNO2 scission confirmed the presence of a well-defined N-acetylated sequence predominantly 9-12 disaccharide units in length proximal to the core protein. Heparinase scission produced two classes of oligosaccharides (Mr approx. 7000 and 15,000) with the general formula: IdoA(2S)-GlcNSO3-[HexA-GlcNR]n-HexA-GlcNSO3 [Hex A-GlcNAc]9 12-GlcA-Gal-Gal-Xyl in which the average value for n is 1-2 for the 7000-Mr species and approx. 22 for the 15,000-Mr species. The latter oligosaccharides extend to about one-third of the total length of the HS chains (Mr approx. 45,000). HNO2 scission of these oligosaccharides enabled hypothetical models for their sequence to be proposed. The general arrangement of N-sulphated and N-acetylated disaccharides between the proximal GlcNSO3 and terminal IdoA(2S) residues of the 15,000-Mr fragment was similar to that in the original polysaccharide, suggesting the possibility of a tandemly repeating pattern in the sequence of HS. PMID- 1859358 TI - Direct electrochemistry of two genetically distinct flavodoxins isolated from Azotobacter chroococcum grown under nitrogen-fixing conditions. AB - Two genetically distinct flavodoxins, designated AcFldA and AcFldB, were isolated from Azotobacter chroococcum (MCD1155) grown under nitrogen-fixing conditions. AcFldA and AcFldB differ in their midpoint potentials for the semiquinone hydroquinone couple (Em -305 mV and -520 mV respectively). Only AcFldB was competent to act as an electron donor to the Mo-containing nitrogenase of A. chroococcum. The N-terminal amino acid sequence (20 residues) of AcFldB was identical with that predicted from the nifF DNA sequence of A. vinelandii OP [Bennett, Jacobsen & Dean (1988) J. Biol. Chem. 263, 1364-1369], suggesting that AcFldB is the nifF gene product of A. chroococcum (MCD1155). Direct fast reversible electrochemistry of these flavodoxins has been achieved at a polished edge-plane graphite electrode using the aminoglycoside neomycin as a promoter. The heterogeneous rates of electron transfer between the graphite electrode and AcFldA and AcFldB were determined to be 1.2 x 10(-3) cm.s-1 and 2.0 x 10(-3) cm.s 1 respectively. The natures of two minor species of flavodoxin designated AcFldC and AcFldD, which were resolved by f.p.l.c., are also discussed. PMID- 1859359 TI - Metabolic substrate utilization by tumour and host tissues in cancer cachexia. AB - Utilization of metabolic substrates in tumour and host tissues was determined in the presence or absence of two colonic tumours, the MAC16, which is capable of inducing cachexia in recipient animals, and the MAC13, which is of the same histological type, but without the effect on host body composition. Glucose utilization by different tissues was determined in vivo by the 2-deoxyglucose tracer technique. Glucose utilization by the MAC13 tumour was significantly higher than by the MAC16 tumour, and in animals bearing tumours of either type the tumour was the second major consumer of glucose after the brain. This extra demand for glucose was accompanied by a marked decrease in glucose utilization by the epididymal fat-pads, testes, colon, spleen, kidney and, in particular, the brain, in tumour-bearing animals irrespective of cachexia. The decrease in glucose consumption by the brain was at least as high as the metabolic demand by the tumour. This suggests that the tissues of tumour-bearing animals adapt to use substrates other than glucose and that alterations in glucose utilization are not responsible for the cachexia. Studies in vitro showed that brain metabolism in the tumour-bearing state was maintained by an increased use of lactate and 3 hydroxybutyrate, accompanied by a 50% increase in 3-oxoacid CoA-transferase. This was supported by studies in vivo which showed an increased metabolism of 3 hydroxybutyrate in tumour-bearing animals. Thus ketone bodies may be utilized as a metabolic fuel during the cancer-bearing state, even though the nutritional conditions mimic the fed state. PMID- 1859360 TI - Interleukin 1 induces the expression of a heat-shock gene in chondrocytes. AB - The presence of T cells and antibodies reactive with heat-shock proteins (hsps) in the joints of patients with rheumatoid arthritis may indicate a role of hsps in this disease. In the present study we examined whether increased temperature and interleukin 1 (IL 1), both of which are elevated in arthritic joints, induced the expression of two hsp70 genes in bovine chondrocyte cultures. We found that heat shock resulted in increased expression of constitutive and inducible hsp70 mRNA species. IL 1 and phorbol 12-myristate 13-acetate (PMA) also induced an increase in the constitutive hsp70 mRNA species, but without affecting the expression of the inducible hsp70 gene. The increase induced by IL 1 was observed only after 3 h, whereas increases induced by PMA were observed within 1 h. For all treatments, the hsp70 mRNA decreased by 24 h. Heat treatment of chondrocytes did not affect levels of collagenase and caseinase activity in the medium, nor did it alter proteoglycan synthesis by these cells. PMID- 1859361 TI - The amino acid sequence of the aspartate aminotransferase from baker's yeast (Saccharomyces cerevisiae). AB - 1. The single (cytosolic) aspartate aminotransferase was purified in high yield from baker's yeast (Saccharomyces cerevisiae). 2. Amino-acid-sequence analysis was carried out by digestion of the protein with trypsin and with CNBr; some of the peptides produced were further subdigested with Staphylococcus aureus V8 proteinase or with pepsin. Peptides were sequenced by the dansyl-Edman method and/or by automated gas-phase methods. The amino acid sequence obtained was complete except for a probable gap of two residues as indicated by comparison with the structures of counterpart proteins in other species. 3. The N-terminus of the enzyme is blocked. Fast-atom-bombardment m.s. was used to identify the blocking group as an acetyl one. 4. Alignment of the sequence of the enzyme with those of vertebrate cytosolic and mitochondrial aspartate aminotransferases and with the enzyme from Escherichia coli showed that about 25% of residues are conserved between these distantly related forms. 5. Experimental details and confirmatory data for the results presented here are given in a Supplementary Publication (SUP 50164, 25 pages) that has been deposited at the British Library Document Supply Centre, Boston Spa. Wetherby, West Yorkshire LS23 7 BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1991) 273, 5. PMID- 1859362 TI - Induction of acyl-CoA-binding protein and its mRNA in 3T3-L1 cells by insulin during preadipocyte-to-adipocyte differentiation. AB - The induction of acyl-CoA-binding protein (ACBP) and ACBP mRNA was investigated in 3T3-L1 cells during growth and insulin-induced differentiation. The level of ACBP relative to both total soluble protein and DNA increased during insulin stimulated conversion of 3T3-L1 cells from preadipocytes into fully developed adipocytes. So did the total rate of lipogenesis, as measured by incorporation of [1-14C]acetate. A similar increase in ACBP mRNA relative to total RNA was observed. These results therefore suggest that ACBP plays a specific role in the lipogenic process. However, this role might be indirect, as the increase in lipogenesis preceded the increase in ACBP. The significance of this finding is discussed. PMID- 1859363 TI - A potent antiplatelet peptide, triflavin, from Trimeresurus flavoviridis snake venom. AB - The interaction of fibrinogen with its receptors on platelet surfaces leads to platelet aggregation. A snake-venom peptide, trigramin, has previously been demonstrated to inhibit platelet aggregation by acting as a fibrinogen-receptor antagonist. By means of gel filtration, ionic-exchange chromatography and reverse phase h.p.l.c., a potent platelet-aggregation inhibitor, triflavin, has now been purified from the venom of Trimeresurus flavoviridis. The purified triflavin is a single-chain polypeptide, consisting of about 71 amino acid residues with a molecular mass of 7600 Da, and its N-terminal sequence is Gly-Glu-Glu-Cys-Asp. Triflavin dose-dependently inhibited human platelet aggregation stimulated by ADP, adrenaline, collagen, thrombin or prostaglandin endoperoxide analogue U46619 in preparations of platelet-rich plasma, platelet suspension and whole blood. Its IC50 ranged from 38 to 84 nM, depending on the aggregation inducer used and the platelet preparation. However, triflavin apparently did not affect the platelet shape change and ATP-release reactions caused by these agonists. Triflavin inhibited fibrinogen-induced aggregation of human elastase-treated platelets in a dose-dependent manner, indicating that it directly interferes with the binding of fibrinogen to its receptors on platelet membranes exposed by elastase treatment. Additionally, triflavin dose-dependently blocked 125I-labelled fibrinogen binding to ADP-activated platelets. In conclusion, triflavin inhibits platelet aggregation through the blockade of fibrinogen binding to fibrinogen receptors on platelet membranes. PMID- 1859364 TI - Molecular comparisons of the beta 2-microglobulin-binding site in class I major histocompatibility-complex alpha-chains and proteins of related sequences. AB - beta 2-Microglobulin (beta 2m) binds non-covalently to the alpha 1, alpha 2 and alpha 3 domains of the alpha-chain of Class I major-histocompatibility-complex (MHC) molecules. On the basis of the crystal structures of human leucocyte antigens HLA-A2.1 and HLA-Aw68.1, we have used molecular-graphics analyses to define 44 contact points between 19 alpha-chain residues and 18 beta 2m residues. In 88 other alpha-chain sequences from the HLA-A, HLA-B, HLA-C, HLA-D, HLA-E, HLA F and HLA-G locus products in man and the H-2, Qa and Tla loci in mouse, 37 contact sites were conserved to 90% or more, and in beta 2m sequences from seven other species 40% of contact sites were totally conserved. Four distinct regions form the contact points between the alpha-chain and beta 2m, one on each of the alpha 1 and alpha 2 domains and two on the alpha 3 domain. We have further studied the alpha-chain sequences of three non-MHC molecules, human CD1 and rat Fc receptor (FcRn), known to bind to beta 2m, and a third molecule, the putative product of the H301 (UL18) gene of human cytomegalovirus (CMV). CMV has been shown to bind beta 2m, and it has been postulated that the H301-gene product, which has sequence similarity to Class I HLA, is the protein responsible. These sequences exhibited much lower residue conservation with the MHC-linked group, although the alpha 3 domain was the most highly conserved, and gaps and insertions were required for optimal alignments with the 90 alpha-chain sequences. Of the 44 beta 2m-alpha-chain contacts defined for Class I HLA, 24 alpha-chain contact sites were conserved in CD1, 25 in FcRn and 17 in the H301 gene product. For CD1 and FcRn, the majority of the conserved beta 2m contacts were found in the alpha 2 domain and the major contact region in the alpha 3 domain. Together with the use of secondary-structure predictions, it was concluded that the binding of beta 2m in CD1 and FcRn was MHC-like at the alpha 3 domain, and probably also at the alpha 2 domain for FcRn, but non-MHC-like for the alpha 1 domain of both molecules and the alpha 2 domain of CD1. In the H301 gene product sequence, only the beta 2m contacts with the main region of the alpha 3 domain were noticeably conserved.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1859367 TI - Specificity of dopachrome tautomerase and inhibition by carboxylated indoles. Considerations on the enzyme active site. AB - Dopachrome tautomerase (EC 5.3.2.3) catalyses the tautomerization of dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) within the melanin-formation pathway. We have analysed a series of substrate analogues and related compounds as possible substrates and inhibitors of tautomerization. The enzyme appears to be highly specific since D-dopachrome, alpha-methyldopachrome, dopaminochrome, adrenochrome methyl ether and deoxyadrenochrome are not substrates. Conversely, dopachrome tautomerase catalyses the tautomerization of dopachrome methyl ester, suggesting that a carboxy group, either free or as a methyl ester, is essential for enzyme recognition. No inhibition of dopachrome tautomerization was observed in the presence of either semiquinonic compounds, such as tropolone and L mimosine, or pyrrole-2-carboxylic acid and unsubstituted indole. However, a number of indole derivatives, including DHICA, the product of dopachrome tautomerization, and the analogues 5-hydroxyindole-2-carboxylic and indole-2 carboxylic acid were able to inhibit the enzyme. Furthermore, indoles with a side chain at position 3 of the ring and containing a carboxylic group at the gamma position of this chain, such as L-tryptophan or indole-3-propionic acid, are stronger inhibitors of the enzyme. Indole-3-carboxylic acid, indole-3-acetic acid and indole-3-butyric acid are very weak inhibitors, showing that the carboxylic group needs to be located at an optimal distance from the indole ring to mimic the carboxylic group at position 2 on the authentic substrate. PMID- 1859365 TI - Activation of membrane protein kinase C by glucagon and Ca(2+)-mobilizing hormones in cultured rat hepatocytes. Role of phosphatidylinositol and phosphatidylcholine hydrolysis. AB - We found that glucagon stimulated membrane protein kinase C (PKC) activity and phosphatidylcholine hydrolysis in 24 h-cultured rat hepatocytes. Phorbol myristate acetate, 8-bromo cyclic AMP, vasopressin, noradrenaline and the Ca2+ ionophore A23187 also stimulated membrane PKC activity. However, only vasopressin and noradrenaline stimulated inositol phosphate accumulation, whereas all agonists stimulated the rate of release of water-soluble choline metabolites into the medium. Choline, and to a much lesser extent phosphocholine, were released, suggesting predominantly phospholipase D activation. This was supported by the finding that the accumulation of phosphatidate and diacylglycerol was enhanced by the agents in [3H]myristate-labelled hepatocytes, as was [32P]phosphatidylethanol formation. Since the time courses for the release of choline into the medium and the accumulation of phosphatidate and diacylglycerol caused by vasopressin and glucagon were similar, the more rapid activation of PKC by vasopressin probably reflects diacylglycerol formation from phosphoinositide breakdown. The inability of glucagon to stimulate inositol phosphate production was not due to the prolonged culture, since similar results were obtained in 4 h cultures. We conclude that the stimulation of membrane PKC activity by glucagon correlates with accumulation of diacylglycerol and phosphatidate derived from the hydrolysis of phosphatidylcholine. PMID- 1859368 TI - Rat liver guanidinoacetate methyltransferase. Proximity of cysteine residues at positions 15, 90 and 219 as revealed by site-directed mutagenesis and chemical modification. AB - Cys-90 of rat liver guanidinoacetate methyltransferase is a very reactive residue, and chemical modification of this residue results in a large decrease in activity [Fujioka, Konishi & Takata (1988) Biochemistry 27, 7658-7664]. To understand better the role of Cys-90 in catalysis, this residue was replaced with alanine by oligonucleotide-directed mutagenesis. The mutant is active and has kinetic constants similar to those of wild-type, indicating that Cys-90 is not involved in catalysis and substrate binding. The u.v.-absorption, fluorescence and c.d. spectra are also unchanged. Reaction of the mutant with an equimolar amount of 5,5'-dithiobis-(2-nitrobenzoic acid) or 2-nitro-5-thiocyanobenzoic acid results in an almost quantitative disulphide cross-linking between Cys-15 and Cys 21). The same treatment effects disulphide bond formation between Cys-15 and Cys 90 in wild type [Fujioka, Konishi & Takata (1988) Biochemistry 27, 7658-7664]. Since the mutant and wild-type enzymes appear to have similar secondary and tertiary structures, these results suggest that Cys-15, Cys-90 and Cys-219 of the methyltransferase occur spatially close together. The mutant cross-linked between Cys-15 and Cys-219 and the wild-type cross-linked between Cys-15 and Cys-90 show very similar spectroscopic properties. Although treatment of the mutant and wild type enzymes with equimolar concentrations of 5,5'dithiobis-(2-nitrobenzoic acid) causes a large loss of enzyme activity in each case, kinetic analyses with the modified enzymes suggest that cross-linking of Cys-15 with Cys-90 or Cys-219 does not abolish activity and does not result in a large change in the Michaelis constants. Incubation of the mutant enzyme with excess 2-nitro-5-thiocyanobenzoic acid leads to modification of Cys-207 in addition to Cys-15 and Cys-219. Retention of considerable enzyme activity in the modified enzyme indicates that Cys-207 is also not an essential residue. PMID- 1859366 TI - Bacterial lipopolysaccharide-stimulated GTPase activity in RAW 264.7 macrophage membranes. AB - The molecular mechanisms surrounding the toxicity and high mortality rate that accompany the release of bacterial lipopolysaccharide (LPS) are unclear, although its potent activity suggests that an amplification system is involved. Because previous studies suggest that a guanine-nucleotide-binding protein (G-protein) may participate in LPS action, we have evaluated the effects of LPS on GTPase activity in membranes isolated from macrophage (RAW 264.7) and fibroblast (B82L) cell lines. LPS induced substantial GTPase activation (200-300% above basal), and kinetic analyses indicated that the maximal LPS-stimulated increase in velocity is observed within 15 min, that it is a low-Km (for GTP) activity, that it can be enhanced by ammonium sulphate, and that it appears to be pertussis toxin insensitive. Moreover, the LPS-enhanced GTPase activity was not antagonized by phosphatase/ATPase inhibitors such as p-nitrophenyl phosphate, ouabain, bafilomycin or N-ethylmaleimide, and in fact was potentiated by the addition of ATP or ADP. Conversely, the LPS precursor, lipid X, which can decrease the lethal effects of LPS, was found to dose-dependently inhibit the LPS-mediated stimulation of GTPase activity. Half-maximal inhibition was seen at the same lipid X/LPS ratio known to be effective in vivo, i.e. 1:1(w/w). These effects appear to be specific because other phospholipids, detergents and glycosides neither stimulated basal, nor inhibited LPS-induced, GTPase activity. These data suggest the involvement of a GTPase in LPS action, and indicate that lipid X may act to directly antagonize LPS at this level. PMID- 1859369 TI - Lobster haemocyanin. Influence of acclimatization on subunit composition and functional properties. AB - Haemocyanin from the lobster Palinurus elephas has been shown to change in its subunit composition according to the time of year. In contrast, in Palinurus mauritanicus, a lobster living at greater depth, no seasonal changes in subunit composition have been observed. The results obtained from a set of experiments performed on some Palinurus mauritanicus acclimatized in an aquarium have clearly indicated that modifications of haemocyanin subunit composition may be involved in the adaptation of arthropods to environmental change. PMID- 1859370 TI - The oligomeric structure of rat and human gastric mucins. AB - Intact oligomeric gastric mucins were isolated from the fundic part of rat and human stomach. Physicochemical properties of the oligomeric mucins from both species, such as buoyant density, molecular mass, proteinase-resistance, amino acid composition and monosaccharide composition were similar. Biochemical analysis showed that the oligomeric mucins from both species consist of disulphide-linked mucin monomers exclusively: no other covalently attached proteins were detected in purified monomeric mucin. Four major differences were found between the monomeric mucins of these species: (1) the human monomer is larger, (2) the proteolytic-digest peptides derived from proteinase-sensitive portions of the polypeptide backbone displayed no sequence similarity, (3) the human mucin was less sulphated compared with rat mucin, and (4) the proteinase sensitive part of the human mucin was relatively larger. However, analyses of [3H]galactose-labelled mucin from both species on gel filtration revealed that both gastric mucins were exclusively synthesized as oligomers. The results indicate that the oligomeric structures of human and rat gastric mucin are similar and their biosyntheses are not affected by the differences in the subunits. PMID- 1859371 TI - Glucose disposal by skeletal muscle in response to re-feeding after progressive starvation. AB - We investigated the extent to which increases in glucose utilization indices (GUIs) in individual skeletal muscles during chow re-feeding after 6 h, 24 h or 48 h starvation are related to the antecedent duration of starvation. Chow re feeding after either acute or prolonged starvation led to an increase in glucose disposal by the muscle mass. Glucose intolerance after prolonged starvation was not associated with lower values of GUI in skeletal muscle. In both working and non-working muscles, the increment in GUI during the first 2 h of re-feeding was less after acute than after prolonged starvation. In non-working muscles the differential responses to re-feeding were due to higher GUI values after re feeding rather than lower pre-prandial GUI values. Therefore the contribution of non-working muscles to glucose clearance is higher as the antecedent period of starvation is extended. Rates of glycogen deposition in non-working muscles after refeeding were similar to absolute values of GUI, and a strong relationship existed between measured GUI values and rates of glycogen deposition. PMID- 1859372 TI - Calmodulin inhibits the protein kinase C-catalysed phosphorylation of an endogenous protein in A10 smooth-muscle cells. AB - The protein kinase C (PKC) activator phorbol 12,13-dibutyrate stimulated the phosphorylation of a 75 kDa protein (p75) in intact cultured A10 smooth-muscle cells and sonicated cell preparations; p75 was the only major substrate for endogenous PKC in sonicated A10 cells. The Ca(2+)-dependent phosphorylation of p75 in vitro was dramatically decreased in PKC-down-regulated A10 cells; however, p75 from identical sonicated cell preparations was still phosphorylated by an exogenous aortic PKC preparation. Calmodulin inhibited the phosphorylation of p75 by PKC, but not the phosphorylation of other PKC substrates (platelet P47 protein and histone). The addition of calmodulin after the phosphorylation reaction was started prevented further phosphorylation, but did not decrease the extent of phosphorylation of p75 that was reached before the addition of calmodulin. The inhibition of p75 phosphorylation was concentration-dependent, with IC50 values (concn. giving 50% inhibition) ranging from less than 0.5 to 10 micrograms of calmodulin/ml, and was Ca(2+)-dependent, requiring a free Ca2+ concentration of 10 microM or greater. These results suggest that the inhibition of the PKC catalysed phosphorylation of p75 by calmodulin may be due to its interaction with the substrate, rather than a direct inhibitory effect on the enzyme, and that this inhibition could be regulated by intracellular Ca2+ concentration. Therefore, p75 may be a physiological link between the PKC and Ca2+/calmodulin pathways. PMID- 1859373 TI - Down-regulation of mannose receptors on macrophages after infection with Leishmania donovani. AB - Macrophages express a mannose-specific endocytosis receptor that binds and internalizes mannose-terminated glycoproteins. Infection of mouse peritoneal macrophages with Leishmania donovani resulted in a decrease in mannose-receptor activity. With 125I-labelled beta-glucuronidase as ligand, a 2-fold decrease in uptake rate was observed in infected cells, with no change in Kuptake. Cell surface binding of 125I-mannose-BSA was diminished 2.5-fold after infection. The decrease in ligand binding appeared to be due to a decrease in the number of sites, with no change in affinity. Elimination of parasites from infected cells by treatment with neoglycoprotein-conjugated methotrexate resulted in an increase in receptor number. Cycloheximide suppressed the drug-treatment-mediated rise in receptor number in infected macrophages. A decrease in receptor activity was also observed in liver Kupffer cells isolated from parasite-infected mice. Binding of ligand by another carbohydrate receptor, the mannose 6-phosphate receptor, was not altered by infection. Phagocytosis of yeast cells was also not altered. These results suggest that mannose receptor synthesis in macrophages is specifically suppressed after infection with Leishmania parasites. PMID- 1859374 TI - Hydrazine is a product of dinitrogen reduction by the vanadium-nitrogenase from Azotobacter chroococcum. AB - During the enzymic reduction of N2 to NH3 by Mo-nitrogenase, free hydrazine (N2H4) is not detectable, but an enzyme-bound intermediate can be made to yield N2H4 by quenching the enzyme during turnover [Thorneley, Eady & Lowe (1978) Nature (London) 272, 557-558]. In contrast, we show here that the V-nitrogenase of Azotobacter chroococcum produces a small but significant amount of free N2H4 (up to 0.5% of the electron flux resulting in N2 reduction) as a product of the reduction of N2. The amount of N2H4 formed increased 15-fold on increasing the assay temperature from 20 degrees C to 40 degrees C. Activity cross-reactions between nitrogenase components of Mo- and V-nitrogenases showed that the formation of free N2H4 was associated with the VFe protein. These data provide the first direct evidence for an enzyme intermediate at the four-electron-reduced level during the reduction of N2 by V-nitrogenase. PMID- 1859375 TI - Properties and structural requirements for substrate specificity of cytochrome P 450-dependent obtusifoliol 14 alpha-demethylase from maize (Zea mays) seedlings. AB - The biochemical properties of cytochrome P-450-dependent obtusifoliol 14 alpha demthylase (P-450OBT.14DM) from maize (Zea mays) seedlings were defined. In particular, the enzyme was shown by differential centrifugation to be localized in the endoplasmic reticulum. P-450OBT.14DM had an apparent Km of 160 +/- 5 microM and an apparent Vmax of 65 +/- 5 pmol/min per mg of protein for its best substrate, obtusifoliol. The substrate specificity of P-450OBT.14DM was thoroughly investigated by comparing the demethylation of obtusifoliol with that of a series of 15 natural or novel synthetic analogues of obtusifoliol. The results obtained clearly indicate that three distinct domains of the sterol substrate are governing obtusifoliol demethylation by P-450OBT.14DM. They revealed that (i) P-450OBT.14DM has probably a specific apolar binding site for the side chain, (ii) the delta 8-double bond is an absolute requirement for substrate demethylation and (iii) the 3-hydroxy group plays a critical role in the enzyme-substrate interaction. Interestingly the binding site, beyond the C-3 position, contains a cleft which cannot accommodate a 4 beta-methyl substituent present in lanosterol or eburicol, the precursors of 14-desmethylsterols respectively in mammals and yeast. This result indicates that P-450OBT.14DM is a novel constitutive cytochrome P-450 with a high degree of substrate and product specificity. PMID- 1859376 TI - The pulmonary surfactant protein C (SP-C) precursor is a type II transmembrane protein. AB - Human pulmonary-surfactant-associated protein C (SP-C) is an extremely hydrophobic peptide comprising 34-35 amino acids. It is involved in the reduction of surface tension at the air/liquid in the lung. In order to understand the mechanism by which this molecule is generated from its 197-amino-acid-residues long precursor and secreted into the alveolar space, we analysed the biosynthesis and processing of this precursor in an 'in vitro' system. Our results show that the SP-C precursor is a 21 kDa integral membrane protein. It is anchored in the membrane by a hydrophobic domain that comprises the 20-amino-acid-residues-long hydrophobic core of the mature SP-C peptide. The N-terminus remains in the cytoplasm, which leads to a type II transmembrane orientation of the precursor. Membrane integration occurs in a signal-peptidase-independent manner. The hydrophobic domain acts as both signal sequence and membrane-anchoring domain. We suggest that correct membrane insertion of the SP-C precursor, which is strictly dependent on the hydrophobic-amino-acid sequence represented by the hydrophobic core of the mature SP-C, is itself a prerequisite for further processing and intracellular transport of the mature SP-C. PMID- 1859377 TI - Hepatic glutathione S-transferases in mice fed on a diet containing the anticarcinogenic antioxidant butylated hydroxyanisole. Isolation of mouse glutathione S-transferase heterodimers by gradient elution of the glutathione Sepharose affinity matrix. AB - Induction of glutathione S-transferases (GSTs) is believed to represent an important mechanism whereby butylated hydroxyanisole inhibits chemical carcinogenesis. The soluble hepatic GSTs expressed by mice fed on normal diets are all homodimers comprising Ya3 (Mr 25,800), Yb1 (Mr 26,400) and Yf (Mr 24,800) subunits. In addition to these constitutively expressed GSTs, we have identified enzymes containing Ya1 (Mr 25,600), Ya2 (Mr 25,600), Yb2 (Mr 26,200) and Yb5 (Mr 26,500) subunits from the livers of Balb/c mice fed on diets containing butylated hydroxyanisole (BHA). Gradient affinity elution of GSH-Sepharose has been used to resolve the mouse liver enzymes into several discrete pools of activity from which GSTs were purified by cation-exchange chromatography. The inducible Mu class Yb2 and Yb5 subunits were separately isolated as the heterodimers GST Yb1Yb2 and GST Yb1Yb5 and their catalytic properties are described; this showed that 1,2-dichloro-4-nitrobenzene and trans-4-phenylbut-3-en-2-one are marker substrates for the mouse Yb1 and Yb2 subunits respectively, but no discriminating model substrate was found that allows the identification of the Yb5 subunit. Individual GST subunits were resolved by reverse-phase h.p.l.c. and their amino acid compositions were determined. Certain subunits (Yb1, Yb2, Yb5 and Yf) were also subjected to automated amino acid sequence analysis, and this demonstrated that the Yb5 subunit has a blocked N-terminus. The mouse Yb1, Yb2 and Yb5 subunits from the major inducible Mu-class heterodimers were cleaved with CNBr and purified peptides from the Yb2 and Yb5 subunits were sequenced. These data show that the Yb2 subunit is distinct from the GSTs that are encoded by the cDNAs that have been cloned from mouse liver cDNA libraries but possesses identity with the protein that is encoded by pmGT2, a cDNA isolated from a mouse fibroblast cell line by Townsend, Goldsmith, Pickett & Cowan [(1989) J. Biol. Chem. 264. 21582-21590]. The sequence data also show that the cDNA encoding the mouse Yb5 subunit has not, to date, been cloned, and the relationship between this subunit and Mu-class GSTs in other species that possess a blocked N-terminus (e.g. rat GST YoYo) is discussed. PMID- 1859379 TI - Inhibition of human leucocyte elastase by ursolic acid. Evidence for a binding site for pentacyclic triterpenes. AB - Several pentacyclic triterpenoid metabolites of plant origin are inhibitors of hydrolysis of both synthetic peptide substrates and elastin by human leucocyte elastase (HLE). Ursolic acid, the most potent of these compounds, has an inhibition constant of 4-6 microM for hydrolysis of peptide substrates in phosphate-buffered saline. With tripeptide and tetrapeptide substrates, the inhibition is purely competitive, whereas with a shorter dipeptide substrate the inhibition is non-competitive, suggesting that ursolic acid interacts with subsite S3 of the extended substrate-binding domain in HLE, but not with subsites S1 and S2. The carboxy group at position 28 in the pentacyclic-ring system of the triterpenes contributes to binding to HLE, since replacement of this group with a hydroxy group, as in uvaol, the alcohol analogue of ursolic acid, reduces the potency of inhibition. The inhibitory potency of ursolic acid is also reduced by addition of 1 M-NaCl, further supporting a postulated electrostatic interaction between the negative charge on the triterpene and a positively charged residue on the enzyme, which we assign to the side chain of Arg-217, located in the vicinity of subsites S4 and S5 in HLE. These observations are consistent with a binding site for ursolic acid which extends from S3 towards S4 and S5 on the enzyme. Other triterpenes, including oleanolic acid, erythrodiol, hederagenin and 18 beta glycyrrhetic acid, can also interact with this binding site. On the basis of these results we conclude that the extended substrate-binding domain of HLE can accommodate a variety of hydrophobic ligands, including not only such molecules as fatty acids [Ashe & Zimmerman (1977) Biochem. Biophys. Res. Commun. 75, 194 199; Cook & Ternai (1988) Biol. Chem. Hoppe-Seyler 369, 629-637], but also polycyclic molecules such as the pentacyclic triterpenoids. PMID- 1859378 TI - Human and sheep growth-plate cartilage type X collagen synthesis and the influence of tissue storage. AB - Direct comparison of type X collagen synthesized by human, sheep and chick growth plate cartilage has shown that the human type X collagen is similar to the chick in both its molecular mass, containing component alpha-chains of 59 kDa with helical regions of 45 kDa, and apparent absence of disulphide-stabilized aggregates, whereas the sheep type X collagen has slightly larger alpha-chains (63 kDa) accounted for by a longer helical region (49 kDa) that contains cystine residues essential for the formation of the high-molecular-mass aggregates found with this species. Type X collagen from all three species showed heterogeneity in primary collagen structure as revealed by Staphylococcus aureus V8 proteinase generated peptide maps. Collagen synthesis by growth-plate cartilage in culture, particularly synthesis of type IX and X collagen, was shown to be very sensitive to prior storage and suggests caution in the interpretation of changes detected when examining collagen synthesis by growth plates in culture. PMID- 1859380 TI - Metabolism in vivo of all-trans-[11-3H]retinoic acid after an oral dose in rats. Characterization of retinoyl beta-glucuronide in the blood and other tissues. AB - Soon after [11-3H]retinoic acid (RA) (1.1 x 10(8) d.p.m.) was administered orally to rats either as a large dose (115 micrograms = 0.38 mumol/rat) or mixed with unlabelled RA as a huge dose (22 mg = 73.33 mumol/rat), retinoyl beta-glucuronide (RAG) was identified and characterized as a significant metabolite in the serum and small intestine. Of the administered dose, 70% remained unchanged as retinoic acid in the stomach up to 1 h. Significant amounts of 5,6-epoxyretinoic acid, 4 hydroxyretinoic acid, esters of retinoic acid and several polar retinoids, including 4-oxoretinoic acid, were also detected in the stomach. No significant difference was observed in the nature of the retinoids found after a large or a huge dose; however, the ratio of RAG/RA was higher after a huge dose than after a large dose. Thus RAG, which is biologically active in vivo and in vitro, is formed quickly in significant amounts in tissues after a dose of RA. PMID- 1859382 TI - An improved assay for pyruvate dehydrogenase in liver and heart. AB - A radiochemical assay was developed to measure pyruvate dehydrogenase complex (PDC) activity in liver and heart without interference by branched-chain 2-oxo acid dehydrogenase (BCODH). Decarboxylation of pyruvate by BCODH was eliminated by using low pyruvate concentration (0.5 mM), a preferred substrate for BCODH (3 methyl-2-oxopentanoate) that is not used by PDC, and a competitive inhibitor of BCODH, dichloroacetate. This method was validated by assaying a combination of both purified enzymes and tissue homogenates with known amounts of added BCODH. The actual percentage of active PDC decreased after 48 h starvation from 13.6 to 3.1 in liver and from 77.1 to 9.0 in heart. Total PDC activity (munits of PDC/units of citrate synthase) in starved rats was increased by 34% in liver and decreased by 23% in heart. Total PDC activity (munits/g wet wt.) in fed- and starved-rat liver was 0.8 and 1.3, and in heart was 6.6 and 5.8, respectively. PMID- 1859381 TI - Increased glucose oxidation and contents of insulin and ATP in polyamine-depleted rat insulinoma cells (RINm5F). AB - In order to elucidate the role of polyamines in the replication and insulin production of insulin-secreting cells, we have investigated the impact of partial polyamine depletion on the proliferation, metabolism, insulin synthesis and ultrastructure of clonal rat insulinoma cells (RINm5F). For this purpose RINm5F cells were exposed for 4 days to the specific ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO). This resulted in a profound decrease in ODC activity and cytoplasmic polyamine contents. The polyamine content of cell nuclei was, however, not altered by DFMO. Addition of small amounts of putrescine during culture elevated the intracellular content of this diamine and suppressed ODC activity. The decrease in polyamine contents was accompanied by a pronounced inhibition of the cellular proliferative activity. The rates of glucose utilization, oxygen uptake and activity of the pentose cycle were decreased in DFMO-treated cells, whereas the glucose oxidation rate, oxidation/utilization ratio, ATP content and ATP/ADP ratio were increased. Insulin mRNA content and synthesis of proinsulin, insulin and total protein were not altered by DFMO. In contrast, there was a sizeable increase in the cellular insulin content, despite a lowered total protein content. Electron-microscopic analysis revealed an accumulation of insulin-secretion granules in the DFMO-treated cells. In addition, short-term insulin release was increased after DFMO exposure, but was not rendered glucose-sensitive. It is concluded that polyamines are necessary for the maintenance of rapid insulinoma-cell replication and that DFMO-treated RINm5F cells acquire an enhanced substrate oxidation and increased content of insulin and ATP. PMID- 1859383 TI - Heparin-polypeptide interaction. Near-i.r. spectroscopy in an anhydrous dispersant allows the involvement of polymer-associated water to be assessed. AB - Involvement of polymer-associated water in the interaction of heparin with poly-L arginine and poly-L-lysine was studied by i.r. spectroscopy of complexes suspended in a non-aqueous dispersant. Movement of i.r. absorption bands due to heparin-associated water to lower frequencies upon polymer interaction indicates that hydrogen-bonding accompanies complexation. We suggest that this bonding includes water bridging between the interacting species, and that the resulting changes in water chemistry may affect the biological activity of such interacting macromolecules. PMID- 1859385 TI - Influence of the trapidil derivative AR 12463 on serum and tissue lipids and development of aortic lesions during experimental atherosclerosis in rabbits. AB - Daily administration of the trapidil derivative AR 12463 (20 mg/kg body weight i.p.) to cholesterol-fed rabbits diminished statistically significantly the increase in serum total cholesterol. After 8 weeks of treatment all measured lipoprotein fractions were significantly lower in animals treated with AR 12463 (group 3) compared with the values of the untreated control (group 1) or vehicle treated group (group 2). The reduction of serum levels was associated with statistically significantly reduced levels of cholesterol esters in kidney, liver and aorta. The levels of free cholesterol in the liver of group 3 animals were statistically significantly lower compared with the levels in the two other groups, whereas in kidney and aortas the levels of free cholesterol remained unchanged under the influence of AR 12463. The area of aorta covered with fatty streaks was significantly smaller in group 3 versus group 1. The results of this study indicate that treatment of rabbits with AR 12463 while feeding a cholesterol-rich diet prevents hypercholesterolemia as well as the cholesterol incorporation into tissues. The mode of action of AR 12463 on serum and tissue lipids as well as on the development of atherosclerosis is discussed. PMID- 1859384 TI - Dose-dependent acinar induction of cytochromes P450 in rat liver. Evidence for a differential mechanism of induction of P450IA1 by beta-naphthoflavone and dioxin. AB - Rats received various doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), Aroclor 1254 (ARO), beta-naphthoflavone (BNF) or phenobarbital (PB), and the hepatic expression of cytochromes P450IA1 and/or P450IIB1/IIB2 was analysed by immunohistochemistry and Western blotting. A clear heterogeneous acinar induction of IA1 was detected when a low dose of TCDD, ARO or BNF was administered. When a low dose of TCDD or ARO was administered, IA1 was found to be induced primarily in hepatocytes located in acinus zone 3, whereas when a low dose of BNF was administered, IA1 was found to be preferentially induced in hepatocytes located in acinus zone 1. A clear zonal induction of IIB1/IIB2 was also observed when a low dose of PB or ARO was administered. Both compounds induced IIB1/IIB2 preferentially in hepatocytes located in acinus zone 3. When rats were administered high doses of TCDD, ARO, BNF or PB there was no zonal pattern of induction of IA1 or IIB1/IIB2; instead, a pan-acinar induction of these enzymes was observed. These results indicate that the overall hepatic concentration of IA1 or IIB1/IIB2 is merely dependent on the proportion of 'induced hepatocytes' within the acinus, which in turn depends on the dose of the inducer. PMID- 1859386 TI - Inhibition of horse liver alcohol dehydrogenase and rabbit muscle lactate dehydrogenase by phenylhydrazine. AB - The activity of horse liver alcohol dehydrogenase was inhibited by phenylhydrazine. Kinetic experiments showed that this compound produced linear competitive inhibition with respect to NAD+ and linear noncompetitive inhibition with respect to ethanol. These results suggested that the inhibitor competes with NAD+ for the coenzyme binding site of alcohol dehydrogenase, forming a dead-end complex with the free form of the enzyme. A Ki value of 393 +/- 51 microM was estimated for the enzyme-inhibitor complex. Further evidence for this mechanism of inhibition arose from the fact that the same kind of inhibition was found for rabbit muscle lactate dehydrogenase. The Ki value for the lactate dehydrogenase phenylhydrazine complex was 43.41 +/- 2.10 mM. The significant difference between these Ki values is explained in terms of known differences in hydrophobicity of the nicotinamide binding region in the two enzymes. PMID- 1859387 TI - Serum albumin stimulates the reactivation of bovine lens epithelial cells in primary culture. AB - Small amounts of serum added to lens epithelial cells in primary culture give rise to an initial retraction of the epithelial sheet and a following stimulation of spreading. It could be shown that albumin or a component tightly bound to albumin is responsible for triggering off these early events of reactivation in culture. The stimulation of spreading is accompanied by an increase of protein biosynthesis. The albumin-produced stimulation of both spreading and protein synthesis are counteracted by adenine or adenosine in the presence of inorganic phosphate. The albumin as well as the purine effects disappear after subculturing of the cells. PMID- 1859388 TI - Erythrocyte rheology and lipid peroxidation in burns. AB - Alterations in the erythrocyte rheology and the contents of activated free radical oxidation products (conjugated dienes, products of thiobarbituric acid and Schiff bases) in the acute phase of experimental thermic injury of the skin were studied. Erythrocyte flexibility reduction and erythrocyte aggregation increase correlated with elevated amounts of free radical oxidation products. Alpha-tocopherol avoided the accumulation of free radical oxidation products and improved both antioxidant defence and erythrocyte rheology. Thus we suppose that free radical oxidation products probably participate in the pathogenesis of erythrocyte rheology disturbances after thermic trauma. PMID- 1859389 TI - Lesion of pontine micturition area in rat causes a severe kidney syndrome. AB - Bilateral symmetric lesions of a small strip in the dorsal pontine reticular formation between the locus coeruleus and the laterodorsal tegmental nucleus caused a severe disturbance of kidney and urinary bladder function beginning with haematuria, micturition paralysis and incontinence on the second postoperative day. Thirteen rats with these lesions were killed on the sixth postoperative day, dissectioned and their kidneys were pathomorphologically investigated. Their urinary bladders were extremely expanded and filled with bloody urine. All kidneys showed a picture of hydronephrosis and were enlarged from 15 mm preoperatively to 30 mm in their longitudinal axis and from 9 to 15 mm in their transverse axis. In seven further rats with partial or asymmetric lesions of this pontine micturition area the micturition cessation and the haematuria disappeared between the 4th and 8th postoperative days: kidney enlargement and hydronephrosis were still found on the 20th postoperative day. PMID- 1859390 TI - Increased acylcarnitine clearance and excretion in septic rats. AB - Carnitine has been hypothesized to be a semi-essential nutrient in the nutrition of critically ill patients. The purpose of this study was to evaluate the effect of sepsis upon carnitine metabolism in the rat, using the model of cecal ligation and puncture. Three treatment groups, septic, sham, and non-operative controls, were used. The septic rats had significantly increased (p less than 0.05) excretion of acylcarnitine and over six-fold higher urinary acylcarnitine/free carnitine ratio, relative to the other two groups. The septic rats also had significantly higher liver and plasma free and total carnitine compared to the other two groups. A possible explanation for the increased urinary acylcarnitine excretion is that carnitine may be acting to remove toxic metabolites from the body. The septic model of cecal ligation and puncture was suitable for the study of carnitine metabolism during sepsis in the rat. PMID- 1859391 TI - Anti-elastin antibodies in rabbits fed an atherogenic diet. AB - Anti-elastin antibodies which seem to play an important role in atherogenesis were studied in serum of rabbits fed with a cholesterol-rich diet using the dot immunobinding assay. These antibodies appeared only in rabbits of the experimental group after the sixth week of the experiment and a progressive rise in their titer was observed. The concentration of total serum cholesterol and the elastase-like activity in aorta which were determined additionally showed a statistically significant increase of both analyzed parameters in animals from the experimental group when compared to the controls. Anti-elastin antibodies seem to reflect an increased elastin turnover during the induction of experimental atherosclerosis. PMID- 1859392 TI - Development of the mammalian gonad: the fate of the supporting cell lineage. AB - Sex determination in mammals is mediated via the supporting cell lineage in the fetal gonad. In the very early stages of gonadal development, the fate of the supporting cell population is critically dependent on the expression of the male determining gene on the Y chromosome. If this gene is absent or fails to be expressed, or is expressed too late or in too small a number of supporting cells, all supporting cells (XX or XY) differentiate as pre-follicle cells and development proceeds along the female pathway. Supporting cells in which the male determining gene is expressed in a timely manner differentiate as pre-Sertoli cells; given sufficient such cells, testis cords form and development proceeds in a male direction. If XX supporting cells are also present, a few may be recruited into the pre-Sertoli population and participate in testis cord formation. The subsequent fate of pre-follicle cells depends critically on interaction with the germ cell population in the developing gonad: absence of germ cells may lead to partial masculinization of the gonad, and/or to disappearance of the supporting cell component. PMID- 1859394 TI - The molecular genetics of alpha 1 antitrypsin deficiency. AB - The human serum protein alpha 1-antitrypsin is the major source of antiprotease activity found in the blood. The protein is synthesised primarily by liver cells but, to a lesser extent, by at least one other cell type. Expression of the gene has provided a paradigm for studies on transcriptional regulation in liver and of tissue-specific promoter activity. The pleiomorphic nature of the gene has given rise to a variety of alpha 1-antitrypsin variants some of which are clinically important. These abnormal variants may be poorly synthesised, rapidly degraded or inefficiently secreted; studies on the molecular mechanisms which underly these events are providing interesting insights into the general processes of protein transport and intracellular protein degradation. PMID- 1859393 TI - Titin, a huge, elastic sarcomeric protein with a probable role in morphogenesis. AB - Titin, the largest protein identified to date (over 1 micron long, almost 3 million daltons in mass) is the third most abundant component of the sarcomere. In the mature myofibril, titin molecules span from M line to Z line, forming a third filament system which provides sarcomeric alignment and elastic recoil. In the developing sarcomere, accumulating evidence from studies both in vivo and in vitro implicates titin as part of a morphogenetic scaffolding, upon which critical events in myofibrillogenesis are coordinated in a time- and space dependent manner. PMID- 1859396 TI - Translational control during early development. AB - Early development in many animals is programmed by maternally inherited messenger RNAs. Many of these mRNAs are translationally dormant in immature oocytes, but are recruited onto polysomes during meiotic maturation, fertilization, or early embryogenesis. In contrast, other mRNAs that are translated in oocytes are released from polysomes during these later stages of development. Recent studies have begun to define the cis and trans elements that regulate both translational repression and translational induction of maternal mRNA. The inhibition of translation of some mRNAs during early development is controlled by discrete sequences residing in the 3' and 5' untranslated regions, respectively. The translation of other RNAs is due to polyadenylation which, at least in oocytes of the frog Xenopus laevis, is regulated by a U-rich cytoplasmic polyadenylation element (CPE). Although similar, the CPE sequences of various mRNAs are sufficiently different to be bound by different proteins. Two of these proteins and their interactions are described here. PMID- 1859395 TI - Actin filaments and photoreceptor membrane turnover. AB - The shape and turnover of photoreceptor membranes appears to depend on associated actin filaments. In dipterans, the photoreceptor membrane is microvillar. It is turned over by the addition of new membrane at the bases of the microvilli and by subsequent shedding, mostly from the distal ends. Each microvillus contains actin filaments as a component of its cytoskeletal core. Two myosin I-like proteins co localize with the actin filaments. It is suggested that one of the myosin I-like proteins might be linked to the microvillar membrane. By interacting with the actin filaments, this motor should move the membrane of a microvillus in a distal direction, thus providing a possible mechanism for the turnover of the membrane. A vertebrate photoreceptor cell contains a small cluster of actin filaments in its connecting cilium at the site where new transductive disk membranes are formed. Disruption of the actin filaments perturbs disk morphogenesis. The most likely explanation for this perturbation is that the process of initiating a new disk is inhibited. Conventional myosin (myosin II) is found in the connecting cilium with the same distribution as actin. A simple model is proposed to illustrate how the actin-myosin system of the connecting cilium might function to initiate the morphogenesis of a disk membrane. PMID- 1859397 TI - An ancient intron in eubacteria: new light on intron origins. PMID- 1859398 TI - Exons--original building blocks of proteins? AB - In a recent paper, Walter Gilbert's group has estimated the number of original exons from which all extant proteins might have been constructed. The approach used is subjected to a critical analysis here. It is shown that there are flawed assumptions about both the mechanism and generality of exon-shuffling and in the sequence comparison procedures employed, the latter failing to distinguish chance similarity from similarity due to common ancestry. These methodological errors lead to the omission of many known cases of exon-shuffling and the inclusion of others which may not be genuine. In consequence, the analysis from the Gilbert group cannot give a reliable estimate of those modules that actually participated in exon-shuffling and provides no information on the number of protein archetypes that did not participate in these processes. PMID- 1859399 TI - Genome mapping: PCR based meiotic and somatic cell hybrid analysis. PMID- 1859402 TI - Dark adapted leaves of paraquat-resistant tobacco plants emit less ultraweak light than susceptible ones. AB - Long term light emission was compared from leaves of paraquat-resistant and susceptible tobacco plants. In the minutes time scale, delayed light emission of the two biotypes was similar both in kinetics and in intensity. However, after several hours in the dark, ultraweak light emission from leaves of resistant plants was about one third of the light emitted by susceptible samples. We suggest, that this difference is due to the higher activity of superoxide dismutase in resistant biotypes, earlier reported by Tanaka et al. (1988) (Plant Cell Physiol. 29, 743-746), and propose a model for the mechanism of ultraweak light emission from these samples. PMID- 1859400 TI - Actin in the Drosophila embryo: is there a relationship to developmental cue localization? AB - Recent genetic manipulations have revealed that the cytoplasm of the early Drosophila embryo contains localized information that specifies the future embryonic axes. It is the restricted distribution or activity of particular gene products, either messenger RNA or protein, that is crucial for this specification. While some of the genes responsible for this information have been sequenced and the nature and distribution of their products examined, it is not known how this localization is established or maintained. The actin-based cytoskeleton is a likely candidate for the formation of a cytomatrix that would allow such distributions and yet no direct evidence has yet been found that implicates actin in positional cue localization. In this review I summarize what is known about actin filament behavior in Drosophila embryos and compare it to the distribution of positional cues. My purpose is to juxtapose these two bodies of information such that the relationship between them may be revealed. PMID- 1859401 TI - Staurosporine inhibits the soluble and membrane-bound protein tyrosine kinases of human neutrophils. AB - Superoxide production by neutrophils triggered with a chemotactic peptide or a phorbol ester is inhibited by the protein kinase antagonists staurosporine or 1 (5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). We evaluated the effects of these antagonists on the protein tyrosine kinases and protein kinase C activities of neutrophils. Staurosporine completely inhibited all of these enzymes, whereas 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine was only substantially effective against protein kinase C. Thus, if a protein tyrosine kinase is involved in superoxide production, it is likely to function with a second kinase sensitive to 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine. PMID- 1859403 TI - Isolation and sequencing of a cDNA clone encoding 85kDa sialoglycoprotein in rat liver lysosomal membranes. AB - We used the oligonucleotide probe corresponding to the internal amino acid sequence of a lysosomal membrane glycoprotein with a molecular weight of 85 K (LGP85) and isolated and characterized cDNA clones containing the entire coding region. The isolated cDNA comprised 2065 nucleotides. The predicted amino acid sequences of LGP85 consisted of 478 amino acid residues (Mr.54,090) and the protein has 11 potential N-glycosylation sites. Since the NH2 terminal sequence determined from purified LGP85 was identical to the NH2 terminal sequence deduced from the nucleotide sequence of the cDNA, except for the lack of initiator methionine which is likely to be cleaved off posttranslationally, it is likely that LGP85 has an uncleavable signal peptide at the NH2 terminus. Hydropathy plots show that LGP85 possesses two strong hydrophobic regions at the NH2 terminus (residues 4-26) and near the COOH terminus (residues 433-457), respectively. Either one or both of the domains might be used for membrane anchoring. A comparison of the sequences of the other lysosomal membrane glycoproteins with that of LGP85 revealed no homology. Glycine-tyrosine residues (so-called GY motif) which are thought an important signal for delivery of lysosomal membrane glycoproteins to lysosomes were not contained in the cytoplasmic tail of LGP85 (residues 458-478). LGP85 appears to be an unique lysosomal membrane glycoprotein that does not require tyrosine residues for targeting to lysosomes. Tyrosine residue may not be an essential signal for delivering newly synthesized lysosomal membrane glycoproteins to lysosomes. PMID- 1859404 TI - Temperature-sensitive synthesis of a metalloproteinase in ts110-MSV-M-transformed NRK cells. AB - Previously, we reported that transformation associated protein (TAP) was over expressed in the 6m2 line, but not in their normal counterparts (1,2). 6m2 is a culture of NRK cells transformed by the ts-110 mutant of MSV-M. The synthesis of TAP and the expression of transformation properties in the 6m2 cells are all temperature-sensitive (2; 3; 4). TAP is secreted as two polypeptides of 64 kD and 68 kD (P64 and P68) (2). Experiments were carried out to determine whether any metalloproteinase (MP) activity was associated with TAP. Results of zymograms indicated that the two forms of purified TAP (P64 and P68) had MP activity, using gelatin or collagen type IV as substrates. Serum-free medium (SFM) of 6m2 cells incubated at 33 degrees C also showed two bands of MP activity, while the corresponding SFM from 6m2 cells at 39 degrees C lacked such MP activity, indicating that the synthesis of MP was temperature-sensitive. The association of MP activity with the P64 and P68 bands of TAP (purified or in SFM) was confirmed by simultaneous Western blot analysis, which showed the reactivity of the two MP bands with monoclonal or polyclonal antibodies to TAP. Accordingly, what we previously designated as TAP is apparently one form of MP, which are known to be involved in tumor cell metastasis. PMID- 1859406 TI - HLA-DR is a procoagulant. AB - Numerous incidents of thromboembolic complications have been documented in cancer patients and in recipients of mismatched organ transplants. Tumor procoagulants have also been implicated in the process of metastasis. Two protein bands of 35,000 and 28,000 daltons isolated from human ovarian carcinoma possessed procoagulant activity. The 35,000 dalton protein had an amino terminal sequence identical to that of the major histocompatibility antigen HLA-DR. Further, isolation of the protein using immunoaffinity column chromatography with monoclonal antibody to HLA-DR resulted in the isolation of procoagulant activity. The immunoaffinity purified protein enhanced thrombin generation in recalcified normal plasma approximately 20- fold. HLA-DR procoagulant activity was completely inhibited by Staphylococcal enterotoxin A. We propose that the procoagulant nature of HLA-DR may contribute to thrombotic disorders in several cancers and in association with graft rejection. The ability of enterotoxin A to inhibit this procoagulant may lead to development of future therapeutic strategies. PMID- 1859405 TI - Lecithin-cholesterol acyltransferase (LCAT) deficiency with a missense mutation in exon 6 of the LCAT gene. AB - The plasma enzyme, human lecithin-cholesterol acyltransferase (LCAT) is responsible for the majority of cholesterol ester formation in human plasma and is a key enzyme of the reverse transport of cholesterol from peripheral tissue to the liver. We sequenced genomic DNA of the LCAT gene from a Japanese male patient who was clinically and biochemically diagnosed as a familial LCAT deficiency. Analysis of all exons and exon-intron boundaries revealed only a single G to A transition within the sixth exon of both allele of the gene, leading to the substitution of methionine for isoleucinle at residue 293 of the mature enzyme. This mutation creates a new hexanucleotide recognition site for the restriction endonuclease Ndel. Familial study of Ndel digestion of the genomic DNA and determination of plasma LCAT activity established that the patient and his sister whose plasma LCAT activity were extremely reduced were homozygous and his children whose plasma LCAT activity were about half of normal controls were heterozygous for this mutation. PMID- 1859407 TI - Cell-density dependent expression of the c-myc gene in primary cultured rat hepatocytes. AB - During culture of mature rat hepatocytes as monolayers, c-myc mRNA was found to be expressed transiently within 2 h, decreasing rapidly to the basal level at 10 h. Then its level increased again to over 10-fold the basal level at 24 h, and remained at this high level during culture. The increase of c-myc mRNA in the second phase was shown by nuclear run-off experiments to be due to an increase of its transcription. The second, but not the first, increase in c-myc expression was inversely proportional to the cell density in culture. The expression of c myc mRNA was not affected by various hormones including growth factors. These results indicate that hepatocytes in culture at lower cell density tend to move from the Go phase to the G1 phase, but remain in the Go phase when cultured at high cell density. PMID- 1859409 TI - The primary structure and elastinolytic activity of medullasin (a serine protease of bone marrow). AB - The amino acid sequence around the carboxyl terminal of medullasin was determined by digesting the protease with carboxypeptidase Y and measuring the rate of release of amino acids from the carboxyl terminal. By considering the structure of the protease's cDNA, we concluded that His-238 is the C-terminal residue of medullasin. Therefore, medullasin is composed of 238 amino acid residues with Ile as the amino terminal and His as the carboxyl terminal. Medullasin is essentially devoid of elastinolytic activity, because it failed to digest orcein-elastin. PMID- 1859408 TI - Fulicin, a novel neuropeptide containing a D-amino acid residue isolated from the ganglia of Achatina fulica. AB - A novel pentapeptide containing a D-amino acid residue was purified from the central ganglia of the African giant snail Achatina fulica Ferussac, and it was named fulicin. The primary structure of the peptide was determined to be Phe-D Asn-Glu-Phe-Val-NH2. Fulicin potentiated tetanic contraction of the penis retractor muscle of this snail at very low concentrations, and also showed modulatory actions on the activity of the buccal and ventricular muscles and the central ganglionic neurons. PMID- 1859410 TI - Molecular cloning and nucleotide sequence of complementary DNA encoding rabbit alpha 1-acid glycoprotein. AB - Alpha 1-acid glycoprotein (AGP) complementary DNA clone has been isolated from an acute phase rabbit liver library. Complete and full-length nucleotide sequence of this cDNA has been determined. The cDNA contains 35 nucleotides 5' untranslated region followed by 606 nucleotides of coding region and a 112 nucleotides 3' untranslated region. Comparison of this sequence with that of human, rat and mouse reveals a high degree of homology with human alpha 1-AGP. Northern blot analysis of messenger RNA for alpha 1-AGP in normal and acute livers demonstrates remarkable induction of transcription of this gene in rabbit in response to acute inflammation by the administration of turpentine. Such a response of AGP gene expression makes it a major member of the acute phase responsive genes in rabbit liver. PMID- 1859411 TI - Role of the C-terminus in the biological activity of human interleukin 5. AB - Alterations of the C-terminal amino acid sequence of recombinant human interleukin 5 (rhIL-5) caused significant changes in its biological activity. Removal of eight amino acids from the C-terminus of rhIL-5 by CNBr treatment led to a complete loss of biological activity as determined by the BCL1 cell IgM inducing assay. Oxidation of Met residue located at C-terminus also resulted in a loss of activity. These results suggest that the C-terminal amino acids of rhIL-5 are crucial for its biological actions. PMID- 1859412 TI - Inhibitory effect of bombesin and SMS 201-995 on DNA synthesis in the rat thyroid lobes incubated in vitro. AB - The effects of 4-h incubation in the presence of bombesin on the incorporation of [3H]-thymidine into DNA of the rat thyroid lobes, collected from animals treated in vivo with a long-acting somatostatin analog (SMS 201-995) or with 0.9% NaCl, were investigated. It was shown that not only in vivo injections of SMS 201-995, but also, unexpectedly, in vitro incubation with bombesin inhibited [3H] thymidine incorporation. The two examined substances did not reveal any additive action in their inhibitory effects on the thyroid growth. PMID- 1859413 TI - Primary structures of the bombesin-like neuropeptides in frog brain show that bombesin is not the amphibian gastrin-releasing peptide. AB - Peptides displaying gastrin-releasing peptide/bombesin-like immunoreactivity were isolated in pure form from an extract of the brain of the European green frog, Rana ridibunda. The primary structure of the more abundant peptide was established as: Gly-Ser-His-Trp-Ala-Val-Gly-His-Leu-Met. NH2. This sequence shows one substitution (Ser for Asn) compared with mammalian gastrin-releasing peptide (18-27) (neuromedin C). The extract also contained gastrin-releasing peptide but bombesin was absent. The data indicate that bombesin is not the amphibian counterpart of gastrin-releasing peptide. PMID- 1859414 TI - N-ethylmaleimide differentiates endothelin converting activity by two types of metalloproteinases derived from vascular endothelial cells. AB - We have recently found that cultured vascular endothelial cells (ECs) contain two types of metalloproteinases which convert big endothelin-1 (big ET-1) to endothelin-1 (ET-1) via a single cleavage between Trp21 and Val22. In the present study, two enzymes were clearly differentiated by using sulfhydryl blocking reagents and anion-exchange HPLC. As reported, the converting activity of the membrane fraction of ECs was specifically inhibited by phosphoramidon. N ethylmaleimide (NEM) markedly enhanced the apparent converting activity of the membrane fraction. This enhancement was not due to the direct action on the converting enzyme, but rather to inhibition of the degradation of big ET-1 and/or ET-1. In contrast, the converting activity of the cytosolic fraction was abolished by NEM treatment. Effects of phosphoramidon and NEM on converting activities of both fractions were confirmed after anion-exchange HPLC of each fraction, using a COSMOGEL QA column. Our results provide new information on two types of metalloproteinases which convert big ET-1 to ET-1, in vascular ECs. PMID- 1859415 TI - Phosphorylation and dephosphorylation modulation of an inverse temperature transition. AB - Poly[15(IPGVG),(RGYSLG)], where RGYSLG is a protein kinase site, was synthesized. On raising the temperature of a 5 mg/ml solution, this polypeptide undergoes an inverse temperature transition at 18 degrees C in which it folds into a contracted state by optimizing intramolecular hydrophobic interactions. Averaging the data of five experiments, phosphorylation by means of a 3':5' cyclic AMP dependent protein kinase to the extent of one phosphate in 360 residues raises the temperature of the folding transition to 32 degrees C. The shift is completely reversed on dephosphorylation by alkaline phosphatase. Phosphorylation is hereby shown to be the most potent chemical perturbation known for shifting the temperature of an inverse temperature transition, which has been shown to be an efficient mechanism for achieving chemomechanical transduction (mechanochemical coupling). PMID- 1859417 TI - The conformation of endothelin-1 in aqueous solution: NMR-derived constraints combined with distance geometry and molecular dynamics calculations. AB - The aqueous solution conformation of the bicyclic, 21 amino acid vasoconstrictor peptide, endothelin-1, has been determined using two dimensional NMR and a combination of distance geometry and molecular dynamics. The dominant structural feature is a helical region between Lys9 and Cys15 characterized by strong NHi NHi+1 NOEs and several long range NOEs spanning 3 to 5 residues. Solvent inaccessibility and possible hydrogen bonding in the Cys3-Cys11 loop is suggested by the temperature independence of the chemical shifts of several amide protons. There is no evidence for association of the C-terminal hexapeptide with the bicyclic region. PMID- 1859416 TI - Fluorescent and photoaffinity labeling derivatives of rhizoxin. AB - A fluorescent probe (D-RZX) and a photoreactive fluorescent probe (AD-RZX) for studying the rhizoxin binding site on tubulin were prepared by the derivatization of rhizoxin (RZX). D-RZX consists of a rhizoxin moiety and a dansyl moiety. AD RZX has a 5-azidonaphthalene-1-sulfonyl moiety instead of the dansyl moiety of D RZX. Both D-RZX and AD-RZX bound tubulin in a mutually competitive manner with rhizoxin, indicating their binding to the rhizoxin site on tubulin. AD-RZX bound the rhizoxin site covalently after UV-irradiation, thus showing its usefulness as a photo-affinity probe for labeling of the rhizoxin site. PMID- 1859418 TI - Initial characterization of several actin genes in the parasitic nematode, Ascaris suum. AB - Southern hybridization data suggest a large actin gene family in Ascaris suum. Our genomic reconstruction experiment indicated that it consists of 50-75 members. Polymorphism was uncovered in the actin genes or in their surrounding sequences. From the genomic library 5 nonoverlapping actin clones were isolated and characterized. PMID- 1859419 TI - Demonstration of a heterogeneous transcription pattern of thyroglobulin mRNA in human thyroid tissues. AB - Previous reports on human thyroglobulin (hTg) modifications in thyroid carcinomas prompted us to study hTg mRNA in thyroid adenomas and carcinomas. The quantification of hTg mRNA showed a decrease in its levels of expression in both pathological conditions which differed by a factor of 2 between adenomas and carcinomas. Furthermore, PCR was used to analyse the characteristics of hTg mRNA by amplifying 4 regions of the hTg mRNA. When applied to 2 normal, 17 benign and 13 malignant pathological tissue specimens, PCR showed no modification in the size of Tg mRNA. However, abnormal sized cDNAs appeared in all tissues with no distinction between the pathologies; the Restriction Fragment Length Polymorphism study of these cDNAs suggests the existence of alternate splicing patterns in thyroglobulin mRNAs. PMID- 1859420 TI - Malonyl-CoA inhibits proteolysis of carnitine palmitoyltransferase. AB - Incubation of isolated mitochondria in the presence of malonyl-CoA prevented proteolysis of the outer carnitine palmitoyltransferase by Nagarse and trypsin. Malonyl-CoA had no direct action on trypsin when present in a chromogenic assay system for proteolysis or when preincubated with the proteases in the absence of mitochondria. As reported previously, Nagarse had a differential effect on carnitine palmitoyltransferase in which malonyl-CoA inhibition was diminished to a greater extent than activity was lost, but all effects were blocked by malonyl CoA in a concentration-dependent manner. These data suggest a specific effect of binding of malonyl-CoA to carnitine palmitoyltransferase as the protective mechanism. PMID- 1859421 TI - Binding specificity of human nuclear protein interacting with the Alu-family DNA repeats. AB - We have demonstrated earlier that human cells contain nuclear protein interacting with conserved GC-rich sequence motifs of human Alu-family DNA repeats. One of these sequences is located in the region between elements A and B of bipartite RNA polymerase III promoter of Alu (AB-region). In this study we have used a DNase I footprinting assay with an Alu restriction subfragment covering AB region, as well as a gel mobility shift assay with appropriate synthetic oligonucleotides to analyse in more detail the interaction of the protein with AB region. We have also used antibodies raised against a zinc-finger peptide to examine the presence of a zinc-finger in the Alu-binding protein. The results indicate that AGG triplets may be important for high-affinity binding of the protein to DNA, and that the Alu-binding protein is a zinc-finger protein. PMID- 1859422 TI - Changes in fibronectin mRNA splicing with in vitro passage. AB - Senescent human fibroblasts produce larger fibronectin molecules with altered binding properties. To determine if this change could involve alternative splicing of fibronectin precursor mRNA, we developed an approach using reverse transcription and the polymerase chain reaction to study fibronectin mRNA splicing at each of the three alternatively spliced regions. Two of the three regions showed changes with in vitro passage incorporation of the ED-A region increased 8 fold. PMID- 1859423 TI - Regulation of arachidonic acid metabolism by phenylarsine oxide. AB - Preincubation of rat liver cells (the C-9 cell line) for 25 min with phenylarsine oxide at levels ranging from 0.06 to 0.6 microM amplifies prostaglandin I2 production when subsequently stimulated by platelet activating factor, lysine vasopressin, bradykinin, thapsigargin, and the Ca2+ ionophore, A-23187, but not that stimulated by exogenous arachidonic acid. The amplification is decreased after preincubation for 25 min with 1.8 microM phenylarsine oxide. Preincubation of mouse lymphoma cells (the WEHI-3 cell line) with phenylarsine oxide at levels ranging from 0.06 to 1.8 microM for 60 min does not affect prostaglandin E2 levels but inhibits leukotriene B4 and C4 production stimulated by the Ca(2+) ionophore, A-23187. Amplification of prostaglandin production by phenylarsine oxide is reversed 100 times more effectively by 2,3-dimercaptopropanol than by 2 mercaptoethanol. Deesterification of lipids appears to be regulated positively in rat liver cells and leukotriene production negatively in mouse lymphoma cells by phosphorylation of tyrosine. PMID- 1859424 TI - Bufalin as a potent inducer of differentiation of human myeloid leukemia cells. AB - Bufalin was found to be a potent inducer of differentiation in human erythroleukemia K562 cells by examination of various differentiation markers (as assessed by the morphology, histochemistry, and the abilities to phagocytose latex particles, to reduce nitro-blue tetrazolium and to develop Fc receptors). Bufalin, at a concentration as low as 10 nM, also produced a strong differentiation-inducing activity in three other human leukemia-derived cell lines (human promyelocytic HL60, monoblastic U937 and myeloblastic ML1). Treatment of K562 cells with other cardiotonic steroids, such as cinobufagin, ouabain and digitoxigenin, at the concentration of 10 nM for four days resulted in weak or no effect on the cells. These findings suggest that bufalin might have potentiality as a new agent in the differentiation therapy for human myelogenous leukemia. PMID- 1859425 TI - Interleukin-4 blocks parathyroid hormone-related protein-induced hypercalcemia in vivo. AB - Interleukin (IL)-4 inhibits bone resorption. In the present study, the effect of IL-4 on hypercalcemia in nude mice under two experimental conditions was assessed. IL-4 inhibited plasma calcium elevation induced by parathyroid hormone related protein (PTHrP) infusion. In hypercalcemic nude mice bearing PTHrP producing tumors, IL-4 lowered plasma calcium levels to almost the normal range. These results indicate that IL-4 blocks PTHrP-induced hypercalcemia in vivo. PMID- 1859426 TI - Ba2+ current oscillation evoked by bradykinin in ras-transformed fibroblasts. AB - By voltage-clamp recording, we show a novel inward current which oscillates after activation with bradykinin or serum in v-Ki-ras-transformed NIH/3T3 cells. The current oscillation was infrequently observed in control NIH/3T3 fibroblasts. The same stimulation evokes Ca2+ oscillations in the ras-transformed cells but not in parental cells (Fu et al., FEBS Lett. 281, 263-266, 1991). The results suggest that the oscillatory currents are generated by influxes of divalent cations to maintain Ca2+ oscillations in ras-transformed NIH/3T3 cells. PMID- 1859427 TI - Subtypes of protein kinase C in isolated nerve growth cones: only type II is associated with the membrane skeleton from growth cones. AB - The growth cone particle (GCP) fraction was isolated from fetal and neonatal rat brains and the distribution of protein kinase C subtypes in the fraction was examined by using subtype-specific antibodies. The main subtype in the GCP fraction from fetal forebrain was type II, and type III was also present, but not type I. The pattern was not altered from embryonic day 17 to postnatal day 5. The membrane skeleton subfraction from the GCP fraction contained type II, but far less amount of type III. Our results suggest that type II and type III may be closely related to the functions of growth cones but that they appear to be associated with distinct signal transduction processes. PMID- 1859429 TI - Inhibition of protein kinase C by semisynthetic phospholipid plasmanyl-(N-acyl) ethanolamine, a nontoxic antitumor preparation. AB - Protein kinase C was extracted from mouse brain and partially purified by ion exchange chromatography on a DEAE-cellulose column. Its activity was determined by incorporation of phosphate from [gamma-32P]ATP into histone H2b. The semisynthetic alkyl-phospholipid plasmanyl-(N-acyl)-ethanolamine (PNAEs) with selective antitumor activity inhibited the activity of the protein kinase in a cell-free system in the presence of phosphatidylserine, a protein kinase C activator. The inhibition was competitive with respect to phosphatidylserine, the inhibition constant being 40 microM. PMID- 1859428 TI - Pertussis toxin blocks melatonin-induced inhibition of forskolin-stimulated adenylate cyclase activity in the chick brain. AB - The high-affinity guanine nucleotide-sensitive receptor sites for melatonin in the mammalian hypothalamus and pars tuberalis mediate inhibition of adenylate cyclase (AC) activity. Therefore, we have examined whether similar sites in the chick brain and retina also modulate AC activity. Melatonin did not alter basal or forskolin-stimulated AC activity in whole forebrain or retinal homogenates. In contrast, melatonin significantly inhibited forskolin-stimulated AC activity in forebrain synaptosomal membranes and partially purified retinal membranes in a concentration-dependent manner. Maximal inhibition (approximately 25-30%) of stimulated AC activity was observed at 10-100nM melatonin, while the concentrations (EC50's) which caused half-maximal effects were 22 +/- 6 pM and 30 +/- 5 pM in the brain and retina respectively. Pretreatment of forebrain slices with pertussis toxin abolished the inhibitory effect of melatonin on stimulated AC activity. These data provide the first evidence that melatonin suppresses AC activity in the chick CNS via a pertussis toxin-sensitive G-protein. PMID- 1859430 TI - Effect of hyperglycemia on acetylcholinesterase and catecholamine levels in rat brain and heart. AB - The effect of hyperglycemia due to experimental diabetes induced in rats, causes a decrease in the activity of Acetylcholinesterase in brain regions and heart; changes in the heart being more significant than the brain. Insulin administration reversed this effect in both the hear and the brain. Significant increase in the levels of catecholamines were also found in the brain regions in diabetes, which was reversed by insulin. The decreased activity of acetylcholinesterase observed in diabetes may be due to an early impaired glucose oxidation and glucose transport as a result of lack of insulin, which causes specific alterations in neurotransmitter levels, thereby effecting blood brain barrier transport, thus causing brain dysfunction. PMID- 1859431 TI - Modulations in nitrogen metabolism in the hepatic and neuronal tissues of fish, Tilapia mossambica exposed to atrazine. AB - The present study deals with the effect of atrazine on nitrogen metabolism in the liver and brain of fish. Significant changes were seen in the levels of proteins, free amino acids, ammonia, urea, glutamine and the activity levels of proteases, glucogenic aminotransferases, branched-chain aminotransferases, glutamate dehydrogenase, glutaminase, arginase, AMP deaminase and adenosine deaminase in both the tissues of fish exposed to sublethal concentration of atrazine. The study reflects a shift in nitrogen concentration of atrazine. The study reflects a shift in nitrogen metabolism in the tissues of fish for efficient mobilization of end products of protein catabolism as a consequence of atrazine. PMID- 1859432 TI - Measurement of brown adipose tissue uncoupling protein by enzyme linked immunosorbent assay. AB - Antibody to uncoupling protein (UCP) purified from rat brown adipose tissue (BAT) was raised in rabbits and an enzyme linked immunosorbent assay was developed. The antiserum did not cross-react with other mitochondrial proteins from BAT and from other tissues but cross-reacted with UCP from hamster, guinea pig and mouse. The assay is capable of detecting 5 ng of UCP. Using this assay and a crude mitochondrial preparation, UCP content of BAT was shown to increase during cold adaptation. PMID- 1859433 TI - Regulation of phosphoenolpyruvate carboxylase from maize leaves by nitrate and alanine. AB - Nitrate and alanine were found to stimulate partially purified maize leaf phosphoenolpyruvate carboxylase under specific assay conditions. Both metabolites stimulated the enzyme at low pH (7.0-7.5) and low substrate levels (1mM phosphoenolpyruvate). Nitrate was found to have a biphasic effect on the enzyme, stimulating at low concentrations (1mM-3mM), with a decrease in stimulation at higher levels. Nitrate caused inhibition of activity at pH 8.0 and although alanine caused some stimulation in activity at pH 8.0 this was not as marked as at the lower pH levels. PMID- 1859434 TI - Changes in mouse brain monoamine oxidase activity in the first, second and fourth generations after manganese administration. AB - The present study was conducted to explore whether or not manganese effect on brain monoamine oxidase (EC 1.4.3.4) is subject to hereditary genetic amplification. Mice of both sexes were given manganese through four generations, and the enzyme activity was measured in the cerebral cortex, cerebellum, hypothalamus and hippocampus of each of the generations except for the third, whose activity we were not in a position to measure. Intrinsic enzyme activity was highest in the cerebellum, and was followed by those in the cerebral cortex and hypothalamus. The activity in the hippocampus was the lowest. Manganese administration greatly stimulated the activity in the cerebellum. However, as generation succeeded, the level of susceptibility to manganese gradually declined. Manganese concentration in pooled suborgan fractions proved to be, in every case, higher in the cerebral cortex, cerebellum and hippocampus and lower in the hypothalamus. No indication was found that the manganese effect is genetically inherited. PMID- 1859435 TI - Comparison of plasma clearance of low density lipoprotein with beta-very low density lipoprotein or acetoacetylated low density lipoprotein in cholesterol-fed rabbits. AB - The plasma clearance and tissue distribution of radioiodinated low-density lipoprotein (LDL), beta-very low density lipoprotein (beta-VLDL), and acetoacetylated LDL were studied in cholesterol-fed rabbits. Radioiodinated LDL ([125I]LDL) was cleared more slowly than either [125I]beta-VLDL or acetoacetylated-[125I]LDL and its fractional catabolic rate was one-half that of [125I]beta-VLDL and one-ninth that of acetoacetylated-[125I]LDL. Forty-eight hours after the injection of the labeled lipoproteins, the hepatic uptake was the greatest among the organs evaluated with the uptake of [125I]LDL being one-third that of either [125I]beta-VLDL or acetoacetylated-[125I]LDL. The reduction in the hepatic uptake of LDL due to a down-regulation of the receptors would account for this retarded plasma clearance. PMID- 1859436 TI - Characterization of gingival epithelium epidermal growth factor receptor. AB - The binding characteristics of gingival epithelium epidermal growth factor (EGF) receptor were investigated using epithelial cell membranes from bovine gingiva. The binding of [125I]EGF was found to be time and protein concentration dependent, reversible, and specific. Unlabeled EGF competed for [125I]EGF binding with IC50 of 0.25nM and maximum displacement of 93% at 0.81nM. Scatchard analysis of the binding data inferred the presence of two binding sites, one of high affinity (Kd = 3.3 nM and Bmax = 47.3fmol/mg protein) and the other of a low affinity (Kd = 1.6 microM and Bmax = 1.9pmol/mg protein). Crosslinking of [125I]EGF to gingival membranes followed by polyacrylamide gel electrophoresis and autoradiography revealed a receptor protein of 170kDa. PMID- 1859437 TI - The possible metabolic diversions adapted by the cockroach, Periplaneta americana to counteract the toxicity of fenvalerate. AB - Effects of sublethal doses of fenvalerate through topical application were monitored in the central nervous system (CNS) of P. americana. A decrease in total and soluble proteins with an increase in free amino acids, alanine aminotransferase (AlAT) and aspartate aminotransferase (AAT) was observed during fenvalerate toxicity. Further the levels of glycogen, pyruvate and activities of succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) dropped significantly. Lactate content and lactate dehydrogenase (LDH) activity also showed an elevation following fenvalerate toxicity. PMID- 1859438 TI - Phosphatidylcholine transfer protein from porcine liver. AB - A phosphatidylcholine transfer protein (PC-TP) of porcine liver was purified to exhibit transfer activity similar to that of bovine liver but with different structural properties. By using hydrophobic Phenyl-agarose column as the last purification step, a 1400-fold purification with 20% yield was attained. Comparative studies on the effects of pH, salt, and temperature on the phosphatidylcholine transfer activity revealed that PC-TP from porcine and bovine livers were similar as far as its activity is concerned. However, the amino acid compositions, the molecular weight, and the elution profiles during protein purification for the two proteins are markedly different. It is suggested that the amino acid composition of PC-TP could be significantly altered without changing its activity and specificity. PMID- 1859440 TI - Degradation and internalization of bound insulin in human erythrocytes. AB - Internalization and degradation of insulin by human erythrocytes were studied. Erythrocytes were incubated with 125I-insulin at 4 degrees C, 15 degrees C, and 37 degrees C for varying time intervals. These erythrocytes were then subjected to a low pH wash to release bound insulin followed by TCA precipitation. After 4, 22, and 24 hours of insulin binding at 4 degrees C, 92 to 95% of the bound 125I insulin was dissociable and 92 to 98% of the extractable insulin was undegraded. After 3.5 hours of incubation at 15 degrees, 82% of the bound insulin was dissociable and 60% of this was intact. However, after 60, 90, 120, and 180 minutes of incubation at 37 degrees C, only 42, 34, 24, and 37%, respectively, of the bound insulin was dissociable. The undissociated insulin in the 37 degrees C studies was considered to be intracellular. With increasing time of incubation at 37 degrees C, the extractability of cell bound insulin and the proportion of undegraded dissociable insulin were decreased. When 125I-insulin binding was 95% blocked by preincubating the erythrocytes with anti-insulin receptor antibody, 95% of the degradation of 125I-insulin was also blocked. These studies indicate that mature human erythrocytes degrade internalized insulin and this process is time, temperature, and insulin receptor dependent. PMID- 1859442 TI - Allosteric antagonists of the muscarinic acetylcholine receptor. PMID- 1859441 TI - Hepatic and renal metallothionein induction in the rat and mouse after treatment with furosemide. AB - Induction of hepatic and and renal metallothionein by furosemide was studied in the rat and mouse. Treatment of mice with 200 and 300 mg/kg furosemide elevated hepatic metallothionein by 117% and 366%, while renal metallothionein was induced by 29% and 380%, respectively. In the rat the drug was less potent i.e. liver metallothionein was increased by 167% and 217% following injection of 300 and 400 mg/kg furosemide, respectively, whereas kidney was not significantly changed by this treatment. The mouse hepatic and renal metallothionein was identified as zinc-containing thionein by Sephadex G-75 gel filtration (Ve/Vo = 2.0). In both species maximal induction was observed 24 hours post exposure. However, the mouse hepatic and renal metallothionein content declined after additional 24 hours whereas the rat metalloprotein was not reduced even after 72 hours of treatment. It is suggested that alterations in metal homeostasis may be responsible for hepatic and renal metallothionein induction caused by furosemide. PMID- 1859439 TI - Glucocorticoids "receptors" in human gingiva. AB - Specific binding of [3H]-dexamethasone by the cytoplasmic fraction of normal human gingiva was carried out. Different concentrations of [3H]-dexamethasone were used with or without cold dexamethasone to determine the binding. Binding data by Scatchard plot yielded a straight line indicating a single class of specific receptors with equilibrium dissociation constant of 1.39 x 10(-9) M and B max of 80 fmol/mg protein. The proteins satisfied the high affinity and low capacity requirements of receptor. PMID- 1859443 TI - Antiprotozoal activity of 3'-deoxyinosine. Inverse correlation to cleavage of the glycosidic bond. AB - Two nucleosides related to the known antiprotozoal agent 1-(beta-D-ribofuranosyl) 1,5-dihydro-4H-pyrazolo-[3,4-d]pyrimidine-4-one (allopurinol riboside, 1) were prepared and evaluated against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma gambiense. 3'-Deoxyinosine (2) exhibited potent antiprotozoal activity against the three protozoal pathogens with minimal toxicity for host cells. It was found to be especially effective against the Columbia strain of T. cruzi reported to be resistant to 1. The antiprotozoal activity of 2 appeared to be inversely related to the rate of cleavage of the glycosidic bond, as shown by metabolic profiles of 2 in the various pathogenic hemoflagellates and host cells. Combining the key structural elements of 1 and 2 led to the synthesis of 1-(3 deoxy-beta-D-erythro-pentofuranosyl)-1,5-dihydro-4H-pyrazolo[3,4-d] pyrimidin-4 one (3'-deoxy-allopurinol riboside, 3). which was found to be inactive as an antiprotozoal agent. PMID- 1859444 TI - Effect of ethanol on phospholipid turnover and calcium mobilization in chick embryos. AB - Effects of ethanol on [3H]inositol and [14C]choline incorporation into phosphatidylinositol (PI) and phosphatidylcholine (PC), free intrasynaptosomal Ca2+ ([Ca2+]i) and synaptosomal 45Ca2+ uptake, were investigated in the brain and heart of 17-day-old chick embryos to which a 10% ethanol solution had been injected on the 3rd day of embryogenesis. In brain synaptosomes, ethanol increased the incorporation of [3H]inositol and [14C]choline into PI and PC, increased [Ca2+]i, and decreased 45Ca2+ uptake. On the other hand, in heart synaptosomal membrane, ethanol decreased the incorporation of [3H]inositol and [14C]choline into PI and PC, decreased [Ca2+]i, and increased 45Ca2+ uptake. Ethanol stimulated in vitro [3H]inositol and [14C]choline incorporation into PI and PC in the brain and heart in both the control and ethanol-treated groups. However, addition of ethanol did not affect the release of 45Ca2+ from the synaptosomal membrane of either organ in either group. Addition of ethanol inhibited 45Ca2+ uptake in a dose-dependent manner in the brain but not in the heart. In both organs, there was a relationship between phospholipid turnover and [Ca2+]i after ethanol. PMID- 1859445 TI - Effect of sorbic acid feeding on peroxisomes and sorboyl-CoA metabolizing enzymes in mouse liver. Selective induction of 2,4-dienoyl-CoA hydratase. AB - On the basis of the finding that sorbic acid (SA)-induced hepatoma was correlated with the depletion of reduced glutathione (GSH) in mouse liver (Tsuchiya et al., Mutation Res 130: 267-262, 1984), the possible conversion of SA to a metabolite which is reactive with SH-compounds was studied. Sorboyl-CoA was hydrated and then reduced to 3-keto-4-hexenoyl-CoA by the combined actions of mitochondrial hydratase (crotonase) and L-3-hydroxyacyl-CoA dehydrogenase. Upon the addition of GSH or coenzyme A, 3-keto-4-hexenoyl-CoA was nonenzymatically converted to another 3-ketoacyl-CoA derivative, possibly a Michael type adduct, in a time- and concentration-dependent manner. Alternatively, sorboyl-CoA can be reduced by 2,4 dienoyl-CoA reductase and completely beta-oxidized without the generation of 3 keto-4-hexenoyl-CoA. Two-week feeding of mice of 15% SA caused a 2.0-fold induction of peroxisome beta-oxidation in the liver. SA caused a marked induction (3.6-fold) of hydratase toward sorboyl-CoA but a less pronounced induction (1.3 fold) of 2,4-dienoyl-CoA reductase, leading to about a 3-fold elevation in the hydratase: reductase ratio. The elevated ratio was sustained throughout the period of SA feeding up to 12 weeks. Thus, a large amount of SA could be converted to 3-keto-4-hexenoyl-CoA during this period. Oxidative stress caused by a depleted cellular SH-pool together with the induction of peroxisome proliferation by SA-feeding may implicate the mechanism by which non-mutagenic SA caused hepatoma. PMID- 1859446 TI - Na(+)-dependent, concentrative nucleoside transport in rat macrophages. Specificity for natural nucleosides and nucleoside analogs, including dideoxynucleosides, and comparison of nucleoside transport in rat, mouse and human macrophages. AB - The effects of natural nucleosides and various analogs thereof on Na(+) dependent, concentrative transport of formycin B by cultured rat macrophages were investigated. Concentrative transport is the sole nucleoside transport system of these cells. The results indicated that uridine, 5'-fluorouridine, all natural purine nucleosides, 2-chloroadenosine and 5'-deoxyadenosine are efficient substrates for the transporter. None of nine other pyrimidine nucleosides was transported. 3'-Deoxy-adenosine, 2',3'-dideoxyadenosine, 8-azidoadenosine, tubercidin, 5'-methylthioadenosine 6-mercaptopurine riboside and adenosine arabinoside were either poor substrates or not transported significantly. The substrate activity of some of the natural nucleosides and the lack of substrate activity of 3'-deoxyadenosine, 2',3'-dideoxyadenosine, 8-azidoadenosine and 2',3' dideoxycytidine were confirmed by direct uptake measurements. No significant concentrative nucleoside transport was detected in cultured human monocytes/macrophages, whereas mouse macrophages possessed both concentrative and equilibrative nucleoside transporters. PMID- 1859447 TI - Inhibition of long-chain acyl-CoA synthetase by the peroxisome proliferator perfluorodecanoic acid in rat hepatocytes. AB - Perfluorodecanoic acid (PFDA) is a potent peroxisome proliferator and is known to affect hepatic lipid metabolism in rats. The effects of PFDA on fatty acid utilization were examined in isolated rat hepatocyte suspensions and in rat liver mitochondria and microsomes. PFDA inhibited the oxidation of palmitic acid but not octanoic or pyruvic acids when hepatocytes were incubated with 1 mM PFDA. At this PFDA concentration the esterification of palmitic acid into triacylglycerols was also reduced. The activity of long-chain acyl-CoA synthetase (ACS), an enzyme essential for both oxidation and esterification of fatty acids, was reduced in hepatocytes incubated with 1 mM PFDA. Carnitine palmitoyltransferase (CPT), an important enzyme for the oxidation of long-chain fatty acids, was not altered in hepatocytes incubated with this PFDA concentration. In rat liver mitochondria, palmitate oxidation and ACS activity were reduced significantly (P less than 0.01) at a PFDA concentration that had no effect on CPT activity. The inhibition of ACS by PFDA was similar in liver mitochondria and microsome preparations. In mitochondria incubated with PFDA, the inhibition of ACS appears to be noncompetitive for the substrates palmitic acid and CoA. However, the ACS inhibition by PFDA appeared to be competitive for the ATP binding site of the enzyme. Several chain length perfluorinated fatty acids were examined for their ability to inhibit mitochondrial ACS. Short-chain perfluorinated fatty acids (perfluoroproprionic and -butyric acid) did not inhibit ACS activity. However, medium-chain perfluorinated acids (perfluorooctanoic, -ananoic and -decanoic acid) were found to be potent inhibitors of ACS in isolated mitochondria. Whether ACS inhibition is causally related to PFDA-induced peroxisome proliferation and altered lipid metabolism seen in vivo is yet to be determined. PMID- 1859448 TI - Differential effects of recombinant interferon alpha on constitutive and inducible cytochrome P450 isozymes in mouse liver. AB - The hepatic cytochrome P450 (P450)-dependent monooxygenase system is subject to regulation by a variety of xenobiotics and endogenous factors. During infection and inflammation the P450 system is usually suppressed, but the factors responsible for this phenomenon and the P450 isozymes involved have not been identified conclusively. We have studied the effects of a specific inflammatory mediator, recombinant interferon alpha, on the constitutive and inducible expression of P450 isozymes (from the CYP1A, CYP2B, and CYP2C) gene families using isozyme preferred substrates and Western blot analysis. Both increases and decreases in P450 levels occurred in response to interferon alpha. Suppression of constitutive P450 isozyme expression occurred and was shown to involve a decrease in steady-state protein expression. The induction of 7-ethoxyresorufin O deethylase activity by 3-MC was potentiated whereas induction of 7 pentoxyresorufin- and 7-benzyloxyresorufin O-dealkylases by PB was suppressed by interferon alpha. These data demonstrate that the effects of interferon alpha on the P450-dependent monooxygenase system are complex, involving differential regulation of several isozymes. Both direct and indirect mechanisms may participate in these phenomena. PMID- 1859449 TI - Soman and sarin inhibition of molecular forms of acetylcholinesterase in mice. Time course of recovery and reactivation by the oxime HI-6. AB - The in vivo sensitivity of the molecular forms of the enzyme acetylcholinesterase to inhibition by either soman or sarin, reactivation by HI-6 and the time course of recovery following inhibition by soman were investigated in mice. Administration of HI-6 (50 mg/kg, i.p.) immediately after soman (100 micrograms/kg, s.c.) or sarin (150 micrograms/kg, s.c.) resulted in an apparent selective reactivation of the 10S and 16S molecular forms of acetylcholinesterase and no reactivation of the 4S form of diaphragm acetylcholinesterase. The apparent selectivity of the reactivation of the molecular forms of the acetylcholinesterase was probably due to the fact that the 10S and 16S forms of acetylcholinesterase are located primarily extracellularly and the 4S form intracellularly. The HI-6 was restricted primarily to the extracellular compartment due to its quaternary, hydrophilic nature. If the administration of HI-6 was delayed until 60 min following soman (100 micrograms/kg, s.c.) injection, no reactivation of any of the molecular forms of acetylcholinesterase could be found in the diaphragm. The soman-inhibited acetylcholinesterase had probably aged and, thus, was not susceptible to reactivation by HI-6. The time course of recovery of the molecular forms in the diaphragm occurred rather quickly with the smaller 4S and 10S forms recovering to control levels faster than the larger 16S form. It took between 8 and 16 days for the 16S form to recover to normal. In the brain, hypothalamic acetylcholinesterase molecular forms such as the 4S recovered faster than the 10S form which had not recovered to control 16 days after soman administration; the 16S form of acetylcholinesterase was not detected in the brain. PMID- 1859450 TI - Cellular pharmacokinetics of carboplatin and cisplatin in relation to their cytotoxic action. AB - We have studied the cellular pharmacokinetics of carboplatin (CBDCA), as part of the evaluation of the antitumor activity of CBDCA in cancers limited to the peritoneal cavity in comparison with cisplatin (cDDP). The uptake of CBDCA into L1210 (lymphosarcoma), CC531 (colonic carcinoma), COV413.B (human ovarian carcinoma) and NB1 (human neuroblastoma) cells was 1.5 to 13 times lower than the uptake of cDDP. The uptake of CBDCA into human ovarian carcinoma cells, taken directly from patients, was also 8-20 times lower than cDDP. Platinum concentrations, expressed as a percentage of the total intracellular Pt concentration, were similar for CBDCA and cDDP in cytosol and nucleus/membrane fractions. A second major difference between the drugs was their binding to DNA. Less CBDCA-DNA than cDDP-DNA adducts were formed after incubation at equimolar amounts of drug with isolated salmon sperm DNA (5-25 times less). A 16-69 times higher concentration of CBDCA than cDDP was needed to induce similar changes in cell growth activity (50% [3H]thymidine inhibition) in CC531 and COV413.B cells, indicating that equitoxicity can only be achieved when tumor cells are exposed to higher concentrations of CBDCA than cDDP. Similar toxicity was achieved in CC531 cells after incubation with a 16-fold higher CBDCA dose than cDDP. Comparable intracellular platinum concentrations, however, were obtained with a 10-fold higher CBDCA dose, suggesting that cellular pharmacokinetics of the drugs are different. Regarding drug uptake and pharmacokinetics the mechanism of action of CBDCA differed from cDDP at a cellular level. PMID- 1859451 TI - Site-specific hypomethylation of c-myc protooncogene in liver nodules and inhibition of DNA methylation by N-nitrosomorpholine. AB - The protooncogene c-myc was investigated in N-nitrosomorpholine-induced rat liver nodules to elucidate the role of altered DNA methylation in chemical carcinogenesis. Furthermore, Micrococcus luteus DNA and chicken erythrocyte DNA were modified in vitro by reactive metabolites of N-nitrosomorpholine, generated by P450-dependent monooxygenases. The modified DNAs were less methylated in vitro than control DNAs by DNA-(cytosine-5)-methyltransferase (DNA methylase). The DNA methylase assay and 32P-postlabeling analysis revealed lowered levels of DNA methylation in nodular DNA. In nodular tissue, c-myc messenger RNA levels were found to be increased compared to normal liver. DNA methylation analysis using the restriction endonucleases HpaII/MspI indicated hypomethylation in the first intron of c-myc DNA in liver nodules. The results suggest that genotoxic lesions may cause stably inherited, aberrant DNA methylation patterns which may be responsible for site-specific hypomethylation of the c-myc protooncogene in liver nodules. PMID- 1859452 TI - Comparison of cytochrome P450 isoenzyme profiles in rat liver and hepatocyte cultures. The effects of model inducers on apoproteins and biotransformation activities. AB - The metabolic profile of seven subfamilies of cytochrome P450 (P450IA, IIA, IIB, IIC, IIE, IIIA, IVA) was studied in rat liver (in vivo) and in primary hepatocyte cultures (in vitro) after treatment with various inducers. The dealkylation of 7 ethoxyresorufin (EROD) and 7-pentoxyresorufin (PROD), aniline 4-hydroxylation and the regio- and stereoselective hydroxylation of testosterone were measured to characterize the isoenzyme pattern in intact hepatocytes and in liver microsomes. Occurrence of isoenzyme apoproteins was determined using Western blotting. Primary cultures of rat hepatocytes retain the capacity to respond to inducers of isoenzymes belonging to six different subfamilies (P450IA, IIA, IIB, IIC, IIIA and IVA). Treatment of cells with beta-naphthoflavone revealed a P450-activity profile similar to in vivo, namely a highly induced EROD (P450IA1), a small enhancement of testosterone 7 alpha-hydroxylation (P450IIA) and a marked reduction in 2 alpha- and 16 alpha-hydroxylation (P450IIC11). Exposure of cultured cells to phenobarbital resulted in a higher testosterone 16 beta hydroxylation (reflecting P450IIB), though to a lesser extent than in vivo. The induction of P450IIIA due to both phenobarbital and dexamethasone, as mirrored by 6 beta- and 15 beta-hydroxylation of testosterone, was the same in cultured hepatocytes and in vivo. Treatment of cells with clofibric acid resulted in an induction profile similar to the one observed in liver microsomes from clofibrate treated rats: the apoprotein P450IVA as well as the apoprotein P450IIB1/2 and its associated activities (PROD and testosterone 16 beta-hydroxylation) were induced. Isoniazid, a known in vivo inducer of P450IIE1 and aniline 4-hydroxylation, did not change any of the determined P450-dependent activities in vitro. PMID- 1859453 TI - Eicosanoid release and mepyramine, LTC4 and LTD4 binding in passively sensitized human lung parenchyma in vitro. AB - In vitro passive sensitization of human lung parenchyma with hyper-immune serum did not affect the release of prostaglandin D2 (PGD2) or leukotriene (LT)-like activity upon challenge with anti-IgE antibody with respect to control lung, despite a marked difference in IgE levels between control (C) and sensitized (S) tissue. Binding studies with [3H]LTC4, [3H]LTD4 and [3H]mepyramine (a histamine H1 antagonist) showed a statistically significant increase in the amount bound in sensitized vs control lung for [3H]mepyramine only. Contractile response to 5 x 10(-5) M histamine (H) in C and S lung parenchymal strips did not correlate with binding data. It is concluded that in vitro elevated IgE levels do not affect the interaction of sulfidopeptide leukotrienes with their putative receptors. As for the observed increase in [3H]mepyramine binding, this might not represent a true increase in histamine receptors on lung smooth muscle cells. PMID- 1859454 TI - Opposite effect of cytochalasin B on agonist-induced respiratory burst in neutrophils and monocytes. AB - The effects of cytochalasin B on the respiratory burst, calcium transients and cell shape change of neutrophils and monocytes has been studied. Cytochalasin B enhanced fMLP-induced respiratory burst in neutrophils whereas the opposite effect, i.e. an inhibition close to 50%, was elicited in fMLP-stimulated monocytes. The differences did not depend on calcium homeostasis. On the basis of cell shape changes, and the well known effect of cytochalasin B on actin polymerization, the opposite effects of cytochalasin B could stem from differences between both cell types concerning the pattern of cytoskeleton membrane interaction which could affect the recruitment and assembly of membrane bound or cytosolic components of NADPH-oxidase. PMID- 1859455 TI - Reversal of melphalan resistance in vivo and in vitro by modulation of glutathione metabolism. PMID- 1859456 TI - Presence of flavin-containing monooxygenase in rat brain. PMID- 1859457 TI - Protective effect of alpha-tocopherol, ascorbic acid and rutin against peroxidative stress induced by oxidized lipoproteins on lymphoid cell lines. PMID- 1859458 TI - Is clonal adaptation a product of evolution over the millennia? PMID- 1859459 TI - Antioxidative properties of harmane and beta-carboline alkaloids. AB - beta-Carboline alkaloids are derived as a result of condensation between indoleamine (e.g. tryptamine) and short-chain carboxylic acid (e.g. pyruvic acid) or aldehyde (e.g. acetaldehyde), a reaction that occurs readily at room temperature. These compounds have been found endogenously in human and animal tissues and may be formed as a byproduct of secondary metabolism: their endogenous functions however, are not well understood. Indoles and tryptophan derivatives exhibit antioxidative actions by scavenging free radicals and forming resonance stabilized indolyl radicals. Harmane and related compounds exhibited concentration-dependent inhibition of lipid peroxidation (measured as thiobarbiturate reactive products) in a hepatic microsomal preparation incubated with either enzymatic dependent (Fe3+ ADP/NADPH) or non-enzymatic dependent (Fe3+ ADP/dihydroxyfumarate) oxygen radical producing systems. Alkaloids with hydroxyl substitution and a partially desaturated pyridyl ring were found to have the highest antioxidative potencies. Substitution of a hydroxyl group by a methoxyl group at the 6-position resulted in a decrease of greater than 10-fold in the antioxidative activities. Harmane showed high efficacy in an enzymatic system but low efficacy in a non-enzymatic system. The antioxidative effects of harmane in the former system may be attributed to its ability to inhibit oxidative enzymes in the microsomal system. These results suggest that beta-carbolines may also serve as endogenous antioxidants. PMID- 1859460 TI - Glutathione-dependent biliary excretion of arsenic. AB - This study aimed to clarify whether glutathione (GSH) plays a role in the hepatobiliary transport of arsenic. For this purpose, the biliary excretion of 74As was measured in urethane-anaesthetized rats for 2 hr after the administration of labelled sodium arsenite (50 mumol/kg, i.v.) or arsenate (150 mumol/kg, i.v.) and under the influence of sulfobromophthalein (BSP), indocyanine green (ICG) or diethyl maleate (DEM) which are known to diminish hepatobiliary transport of GSH. Although the biliary excretion of arsenic was different after arsenite and arsenate administration in terms of quantity (19% vs 6% of dose in 2 hr, respectively) and time course, arsenic excretion responded similarly to BSP (50 mumol/kg, i.v.), ICG (25 mumol/kg, i.v.) or DEM (4 mumol/kg, i.p.) irrespective of the injected arsenical. Initially the biliary excretion of arsenic in rats with either arsenite or arsenate was significantly reduced, but then moderately increased by BSP and, more lastingly, depressed by ICG, whereas it was virtually abolished by DEM. The responses of arsenic excretion to BSP, ICG and DEM were related, both proportionally and temporally, to the effects exerted by these agents on the hepatobiliary transport of GSH, as assessed by the biliary excretion of non-protein thiols. These findings indicate that the biliary excretion of arsenic after the administration of either arsenite or arsenate is dependent on the hepatobiliary transport of GSH. Transport of arsenic as a GSH complex may account for the GSH dependence of biliary arsenic excretion. PMID- 1859462 TI - Effect of the aging process on the gender and phenobarbital dependent expression of glutathione S-transferase subunits in brown Norway rat liver. AB - The effect of age, gender and phenobarbital treatment on the hepatic cytosolic glutathione S-transferase subunit composition was studied in Brown Norway rats. Affinity chromatography followed by reversed phase HPLC was used in order to separate the various glutathione S-transferase subunits. Corresponding steady state mRNA levels were measured by Northern Blot analysis using cDNA clones hybridizing to mRNA encoding glutathione S-transferase subunits 1/2, 3/4 and 7, respectively. In all the age groups studied (15, 25, 53, 99, 112 and 136 weeks) the total amount of glutathione S-transferase protein was in untreated rats significantly higher in males (132 micrograms/mg cytosolic protein) than in females (91 micrograms/mg cytosolic protein) and significant gender dependent differences in the subunit composition were demonstrated. Aging seemed to be of minor importance in untreated as well as in phenobarbital treated rats. Under control conditions, the subunit composition of male rats between 15 and 136 weeks old consisted of 28, 12, 11 and 49% of subunits 1, 2, 3 and 4 respectively and of female animals of the same age groups of 38, 26, 7 and 30%, respectively. In all the age groups studied phenobarbital administration (45 mg/kg body weight, i.p., once a day for 7 days) doubled total glutathione S-transferase protein in both genders and affected the subunit composition in a significant way, emphasizing the already existing differences between genders. Subunits 1, 2 and 3, especially, were increased in male rats in comparison to females resulting in the observation that levels of glutathione S-transferase subunits studied became higher in males than in their female counterparts. The HPLC results were confirmed by steady-state mRNA analysis. In untreated rats, higher levels of mRNA encoding glutathione S-transferase subunits 1/2 and 3/4 were present in male than in female livers. Phenobarbital treatment increased mRNA levels in both genders. Subunit 7 was never detected. These effects were demonstrated in both young and old rats. PMID- 1859461 TI - Elevation of delta-aminolevulinic acid synthase and cytochrome PB1 P450 messenger RNA levels by dihydropyridines, dihydroquinolines, sydnones, and N ethylprotoporphyrin IX. AB - A series of compounds that increase the activity of delta-aminolevulinic acid synthase (ALAS) in chick embryo hepatocyte cultures were studied for their effects on steady-state levels of mRNA for ALAS and phenobarbital-inducible cytochrome PB1 P450. N-Ethylprotoporphyrin IX (N-EtPP), which is believed to lower heme levels by inhibition of ferrochelatase (FC), had little effect on steady-state ALAS mRNA levels. 3,5-Diethoxycarbonyl-1,4-dihydro-2,6-dimethyl-4- isobutylpyridine (4-isobutyl DDC), which is believed to lower heme levels by repetitive destruction of the heme moiety of cytochrome P450, increased steady state levels of ALAS mRNA levels approximately 2-fold. 3,5-Diethoxycarbonyl-1,4 dihydro-2,6-dimethyl-4-ethylpyridine (4-ethyl DCC) which inhibits FC activity and destroys the heme moiety of cytochrome P450, increased ALAS mRNA levels approximately 4-fold. A combination of N-EtPP and 4-isobutyl DDC produced a synergistic increase in ALAS mRNA levels to approximately 6-fold over control levels. The synergistic increase in ALAS activity observed previously with this combination can be explained, at least in part, by a synergistic increase in ALAS mRNA levels. Other porphyrinogenic agents, which function as mechanism-based inactivators of cytochrome P450 and elevate ALAS activity, were found to elevate ALAS mRNA. These compounds included 3-[2-(2,4,6-trimethylphenyl)thioethyl]-4 methylsydnone (TTMS), 2,4-diethyl-2-methyl-1,2-dihydroquinoline (DMDQ), and 2,2,4 trimethyl-1,2,dihydroquinoline (TMDQ). The elevation of ALAS mRNA by these porphyrinogenic agents is probably due to their lowering of cellular heme levels by a combination of ferrochelatase inhibition and repetitive destruction of the heme moiety of cytochrome P450. The lowering of heme levels should result in an enhancement of ALAS mRNA half-life as it has been demonstrated by others that heme shortens the half-life of ALAS mRNA. It was of interest that some of these drug treatments also caused an elevation in steady-state levels of cytochrome PB1 P450 mRNA; the exception was TTMS, which along with its analogue 3-(2 phenylethyl)-4-methylsydnone (PEMS), did not alter cytochrome PB1 P450 mRNA levels. Increases in steady-state levels of cytochrome PB1 P450 mRNA subsequent to increases in steady-state levels of ALAS mRNA were observed with 4-ethyl DDC, 4-isobutyl DDC, DMDQ, and TMDQ. The data obtained with N-EtPP and a combination of N-EtPP and 4-isobutyl DDC on cytochrome PB1 P450 mRNA levels do not support the contention that heme functions as a positive regulator of cytochrome P450 gene expression. PMID- 1859463 TI - Inhibition of 2-desamino-2-methyl-10-propagyl-5,8-dideazafolic acid cytotoxicity by 5,10-dideazatetrahydrofolate in L1210 cells with decrease in DNA fragmentation and deoxyadenosine triphosphate pools. AB - 5,10-Dideazatetrahydrofolate (DDATHF) is an antifolate drug, the cytotoxic effects of which can be fully reversed by hypoxanthine, suggesting that DDATHF exerts its effects by inhibiting de novo purine biosynthesis. ICI198583 is a quinazoline based inhibitor of thymidylate synthase. In this study we examine the interaction between treatment of mouse leukaemic L1210 cells with these drugs. The addition of DDATHF with ICI198583 was correlated with a decrease in ICI198583 cytotoxicity in a dose dependent manner. This protection was associated with a decrease in DNA fragmentation, and a drop in intracellular dATP pools. These results support the hypothesis that inhibitory effects on de novo purine biosynthesis by inhibitors of dihydrofolate reductase may limit cytotoxicity, and indicate that a rise in dATP pools may be an important cytotoxic signal. PMID- 1859464 TI - Effects of ethanol consumption on bioactivation and hepatotoxicity of N nitrosodimethylamine in rats. AB - To study the effects of ethanol on the hepatotoxicity of N-nitrosodimethylamine (NDMA), 5 mg NDMA/kg body weight was injected intraperitoneally 3 times a week for 6 weeks into rats pair-fed liquid diets containing 36% of energy either as ethanol or as additional carbohydrates. Another group of rats was pair-fed with the same diets but injected with saline instead of NDMA. Co-administration of ethanol and NDMA produced much higher elevations of serum alanine and aspartate aminotransferase and glutamic dehydrogenase activities than the administration of either agent alone. The combined treatment also slightly increased focal necrosis, whereas other liver lesions (steatosis and fibrosis) and the functional impairment of mitochondrial respiration were not affected significantly. Microsomal low Km NDMA demethylation, as well as NDMA denitrosation, were inhibited markedly by incubation with an antibody against P450IIE1, suggesting the involvement of this alcohol-inducible P450 in both NDMA bioactivation reactions. The addition of ethanol inhibited P450-dependent demethylation and denitrosation of NDMA in liver microsomes, whereas both activities were enhanced markedly by chronic ethanol administration. At ethanol concentrations similar to those prevailing in the blood of alcohol-fed animals at the time of NDMA administration, hepatic microsomal demethylation and denitrosation remained significantly higher in ethanol-fed rats given NDMA than in controls. Our results suggest that bioactivation plays a critical role in the hepatotoxicity of NDMA and its aggravation by chronic alcohol consumption. PMID- 1859465 TI - Relationships between energy level and insulin secretion in isolated rat islets of Langerhans. A study at various pH values. AB - To define better the role of [ATP]/[ADP] in insulin release from pancreatic islets, changes in the adenine nucleotide ratios elicited by alterations in external pH were correlated with the secretion profiles produced by administration of two metabolic secretagogues, 16 mM glucose and 10 mM alpha ketoisocaproic acid. Experiments were carried out in buffers with and without bicarbonate, in the pH range 6.5-7.7. Insulin release was dependent on pHe irrespective of the secretagogue used. Secretion profiles for alpha ketoisocaproic acid were the same both with and without bicarbonate; the release was decreased below pH 7.1 but maintained at 7.4-7.7. The same pattern was seen with glucose in media buffered with Hepes. With bicarbonate present, secretion caused by high glucose showed a bell-shaped dependence on [H+], with reductions at the acid and alkaline sides of pH 7.1-7.4. [ATP] and [ADP] were higher when Hepes was the buffer, at all pH values studied. The [ATP]/[ADP] declined with increasing pH under both basal and stimulated conditions; the values were always larger after stimulation although at pH 7.7 with bicarbonate present and glucose as the stimulant the difference was very small. It is concluded that: (i) the [ATP]/[ADP] in pancreatic islets is markedly dependent on pHe; (ii) there is no straight-forward correlation between either [ATP] or the absolute value for [ATP]/[ADP] and insulin secretion; and (iii) a rise in [ATP]/[ADP] is necessary for glucose-stimulated insulin release although it is not always the rate determining event. PMID- 1859466 TI - Evidence for the in vivo formation of ascorbic acid 2-O-alpha-glucoside in guinea pigs and rats. AB - In vivo formation of ascorbic acid 2-O-alpha-glucoside (AA-2G) in guinea pigs and rats given ascorbic acid (AA) orally in combination with maltose was examined. A metabolite of AA which has the same HPLC retention characteristics as authentic AA-2G was detected in the blood, urine and liver of guinea pigs 1-2 hr after their administration. The metabolite was isolated from the urine by chromatographic procedures and identified as AA-2G by its UV spectrum, non reducibility, susceptibility to alpha-glucosidase hydrolysis, HPLC profile and elementary analysis. The same glucoside was also synthesized by rats and found in the urine, although it could not be determined qualitatively in the blood. AA-2G forming activities of tissue homogenates from both animals were apparently correlated with their alpha-glucosidase activities and, moreover, both activities were completely inhibited by a specific neutral alpha-glucosidase inhibitor. Thus, we conclude that AA-2G is a possible metabolite produced by enzymatic alpha glucosidation after a combined administration of AA and maltose to guinea pigs and rats. PMID- 1859467 TI - Protection from CCl4 toxicity by prestimulation of hepatocellular regeneration in partially hepatectomized gerbils. AB - The present investigation was undertaken to test our hypothesis that the slow responses of hepatocellular regeneration and tissue repair after CCl4-induced liver injury are responsible for the high sensitivity of gerbils to the hepatotoxic and lethal effects of CCl4. These studies were conducted in normal and actively regenerating livers using male gerbils 5 or 15 days after partial (2/3) hepatectomy (PH5 and PH15, respectively), or those undergoing sham operation (SH). An LD50 dose of CCl4 (80 microL/kg, i.p.) resulted in a mortality (21%) significantly (P less than 0.05) less than 50% in PH5 gerbils 48 hr after CCl4 administration, whereas the mortality observed in PH15 or SH gerbils was not significantly different from 50%. The elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly (P less than 0.05) less in PH5 gerbils than in PH15 or SH groups after the administration of either the LD50 dose or a low dose (15 microL/kg) of CCl4. Histopathological and histomorphometric examinations also indicated that CCl4-induced liver injury was less severe in PH5 gerbils than in the PH15 and SH groups. The hepatic microsomal cytochrome P450 content measured before CCl4 administration in the PH5 gerbils was decreased (26%) significantly (P less than 0.05) as compared with the SH group, but was not significantly different from that of PH15 gerbils. In vivo metabolism of 14CCl4 and lipid peroxidation in liver tissue were not significantly different among the various groups. Therefore, the protection against CCl4 toxicity observed in PH5 gerbils is unlikely to be due to decreased bioactivation of CCl4 or lipid peroxidation in that group. [3H]Thymidine incorporation into hepatocellular nuclear DNA was 4- to 5-fold higher in PH5 gerbils than in the PH15 and SH groups, indicating active hepatocellular proliferation in PH5 gerbils. [3H]Thymidine incorporation was further increased significantly (P less than 0.05) 24 hr after challenge with a low dose of CCl4 in PH5 gerbils, whereas it remained low until 48 hr after the CCl4 injection in the PH15 or SH group. The protection against CCl4 toxicity afforded by partial hepatectomy was closely associated with active hepatocellular regeneration. The overall results confirm the concept that the high sensitivity of gerbils to CCl4 is due to very sluggish hepatocellular regeneration and tissue repair response to the CCl4-induced liver injury. PMID- 1859468 TI - 86Rubidium efflux and negative inotropy induced by P1- and muscarinic-receptor agonists in guinea-pig left atria. Effects of potassium channel blockers. AB - Guinea-pig isolated left atria, paced at 2 Hz were incubated with 86rubidium (86Rb) for 120 min. They were then washed every 2 min for 2 hr, each sample being retained for scintillation counting. Left atrial isometric tension was recorded simultaneously. A concentration-response curve for the muscarinic agonist carbachol or the P1-receptor agonists adenosine and L-N6-phenyl isopropyladenosine (L-PIA) was obtained. Antagonists were present from 20 min before agonist exposure. The rate constant (k) for 86Rb efflux was calculated for each 2 min sample and the mean increase for each concentration of agonist determined. In the absence of drugs there was no significant alteration in the rate constant during the 2 hr experimental period. Adenosine, L-PIA and carbachol produced concentration-related increases in rate constant for 86Rb efflux. The adenosine and L-PIA concentration-response curves were virtually superimposed upon the curves for the negative inotropic responses. The 86Rb efflux induced by adenosine was antagonized in an apparently parallel manner by 8 phenyltheophylline (8-PT) indicating involvement of P1-receptors. Alone, the putative potassium channel blockers, 4-aminopyridine (4-AP) and bromobenzoylmethyladamantylamine (BMA) caused, respectively, no change and a reduction in resting 86Rb efflux immediately prior to the agonist exposure. 4-AP reduced the L-PIA- and adenosine-induced increases in 86Rb efflux and, to a lesser extent, the negative inotropic response to adenosine. BMA caused "flattening" of the dose-response curves for 86Rb efflux induced by L-PIA, adenosine and carbachol with a significant reduction in response at the highest concentrations of adenosine and carbachol. The negative inotropic response to adenosine was also reduced. These results suggest that 4-AP and BMA block the P1 receptor-linked potassium channels and that BMA interacts with common K+ channels linked to P1- and muscarinic receptors. The negative inotropic responses of the guinea-pig left atrium to P1- and muscarinic agonists can be attributed, at least in part, to the opening of outward K+ channels. PMID- 1859469 TI - Inhibition of phosphorylation of troponin I in rat heart by adenosine and 5' chloro-5'-deoxyadenosine. AB - We have investigated the effects of adenosine on protein phosphorylation in extracts of rat heart. Incubation of a myofibrillar fraction with [gamma-32P]ATP resulted in the phosphorylation of several proteins by endogenous protein kinases. The adenosine analog 5'-chloro-5'-deoxyadenosine inhibited the phosphorylation of a 29 kD protein in this preparation. The protein was identified as cardiac troponin I (cTnI) by two-dimensional gel electrophoresis, using purified cTnI as standard. Addition of the catalytic subunit of cAMP dependent protein kinase to the myofibrillar fraction increased phosphorylation of cTnI; this increase was inhibited by 5'-chloro-5'-deoxyadenosine and adenosine. Phosphorylation of purified cTnI by the catalytic subunit was also inhibited by 5'-chloro-5'-deoxyadenosine. Under these conditions used, 50% inhibition of phosphorylation by either endogenous or exogenous kinase was observed at approximately 50 microM 5'-chloro-5'-deoxyadenosine or adenosine. The inhibition described here occurred independently of catecholamines. The effects of ADP, AMP, and adenine on cTnI phosphorylation are also described. PMID- 1859470 TI - Selective 3-hydroxylation deficiency of lidocaine and its metabolite in Dark Agouti rats. AB - Selective and marked 3-hydroxylase deficiency of lidocaine and its N-deethylated metabolite, MEGX, were observed in male and female DA rats. These findings suggest that cytochrome P450 isozymes metabolizing debrisoquine may be involved in the 3-hydroxylations of lidocaine and MEGX in rats and humans. PMID- 1859471 TI - Glutathione transferase mu deficiency is not a marker for predisposition to sulphonamide toxicity. AB - Glutathione transferase mu activity, a marker for susceptibility to lung cancer and chemically induced cytogenetic damage, is not a predictive index for the predisposition to sulphonamide hypersensitivity reactions. However, considering the functional diversity and broad, overlapping substrate specificity of GSH dependent enzymes, it is conceivable that an as yet unidentified deficiency in another GST isozyme or GSH-related enzyme may be a marker for sulphonamide toxicity. In addition, heterogeneity in cellular repair mechanisms and the diversity of the human immune response [22] may also contribute to the manifestation of the toxic effects of sulphonamides. Experiments are currently in progress to determine which of this myriad of variables is predominantly responsible for inter-individual susceptibility to the idiosyncratic reactions produced by these antibacterial agents. PMID- 1859472 TI - Dose- and time-dependent effect of an acute 3-amino-1,2,4-triazole injection on rat brain catalase activity. AB - The results presented in this study demonstrate a progressive inhibition of rat brain catalase activity by AT in vivo. Furthermore, the inhibition of brain catalase by AT demonstrates the presence of hydrogen peroxide in brain, since AT inhibits catalase in the presence of this compound. The rate of inhibition of catalase seems to be dependent upon the rate by which H2O2 is generated. A time course study showed slower onset of the inhibition of brain as compared to liver catalase, possibly reflecting tissue hydrogen peroxide levels or, alternatively, a rate-limiting penetration of AT into brain and into the catalase compartment. The presence of AT in brain was confirmed over the time period of the observed inhibition of brain catalase. Catalase inhibitors are of particular interest in the study of the physiological role of catalase. This study further supports the use of AT in investigations designed to further understand the role of brain catalase. PMID- 1859473 TI - Drug oxidation and N-acetylation in rats pretreated with subtoxic doses of streptolysin O. AB - SLO in sublytic doses (100 HU/kg body wt) depressed the hepatic microsomal cytochrome P450 and aminopyrine-N-demethylase but increased significantly the cytosolic N-acetyltransferase after acute and subacute (5 days) pretreatment of male Wistar rats. Aniline hydroxylase was reduced after acute and unchanged after subacute pretreatment. The effects of SLO on the oxidative enzymes and drug N acetylation might have been caused by the membranal and immunological properties of the toxin. PMID- 1859474 TI - Effect of experimental cirrhosis on cholephilic dye metabolism and excretion in the rat. PMID- 1859475 TI - Transport of 2'-deoxycoformycin in human leukemic and lymphoma cells. PMID- 1859476 TI - Protective effects of propylene glycol, a solvent used pharmaceutically, against paracetamol-induced liver injury in mice. PMID- 1859478 TI - Treatment of collagen-induced arthritis in rats with a monoclonal antibody against the alpha/beta T cell antigen receptor. AB - A monoclonal antibody (MAb) to the alpha/beta T cell receptor (TCR alpha/beta), R73 MAb, completely blocked the induction of collagen-induced arthritis (CIA) in rats when the MAb was administered at the time of immunization with type II collagen. When administered after CIA had begun, the progression of the arthritis was suppressed significantly by R73 MAb treatment. The preventive and suppressive effects of R73 MAb on CIA were associated with the depletion of peripheral blood alpha/beta-positive T cells. These results indicate that alpha/beta-positive T cells play a role in the progression of existing CIA as well as in its induction. PMID- 1859477 TI - Modulation of interleukin-1-induced alterations in cartilage proteoglycan metabolism by activation of protein kinase C. AB - Interleukin-1 (IL-1) stimulates proteoglycan degradation and prostaglandin E2 (PGE2) release and inhibits proteoglycan synthesis by cartilage in organ culture. Addition of the protein kinase C (PKC) activator, mezerein, resulted in the concentration-dependent inhibition of IL-1 activity on proteoglycan metabolism. Similar effects were seen with other compounds which stimulated PKC, such as teleocidin B4 and phorbol dibutyrate (PDBu), but not with a phorbol analog that is inactive in stimulating PKC. Simultaneous addition of the PKC antagonist, staurosporine, blocked the mezerein-induced inhibition of IL-1 activity on both proteoglycan degradation and synthesis in a concentration-related manner. In contrast to its inhibition of the effect of IL-1 on proteoglycan metabolism, mezerein did not block the release of PGE2 by cartilage in response to IL-1 but caused a synergistic stimulation of PGE2 release. Importantly, in cultures made deficient in PKC by prolonged incubation with PDBu, the effects of this PKC agonist on proteoglycan breakdown and PGE2 were blocked, while stimulation by IL 1 persisted. These data indicate that the effects of IL-1 on proteoglycan metabolism and prostaglandin production are mediated by an intracellular signal distinct from PKC and suggest that activation of PKC in chondrocytes may play a role in modulating the action of IL-1 on proteoglycan metabolism. PMID- 1859479 TI - Enkephalinase: a physiologic neuroimmunomodulator detected in the synovial fluid. AB - Enkephalinase (endopeptidase 24.11) is a metallopeptidase that is able to cleave not only neuropeptides and hormones but also immune mediators. The enzyme was quantified in synovial fluid obtained from 36 swollen joints. Its concentration correlated with the synovial fluid cell count, mainly the polymorphonuclear cells and lymphocytes, and with the erythrocyte sedimentation rate. No statistically significant difference in enkephalinase levels was demonstrated between the groups of patients with rheumatoid arthritis, seronegative spondylarthropathy, microcrystalline arthritis, or osteoarthritis. The presence of enkephalinase in the synovial fluid could reflect the intensity of the inflammatory process, or it could represent a physiologic regulator of inflammation and pain within the joint. PMID- 1859480 TI - Cerebral vasculopathy associated with collateralization resembling moya moya phenomenon and with anti-Ro/SS-A and anti-La/SS-B antibodies. AB - We describe a 48-year-old, previously healthy, anti-Ro/SS-A and anti-La/SS-B antibody positive black woman with negative risk factors for atherosclerosis, who developed mental status and personality changes over a 6-12-month period, and progressive cortical blindness over a 2-week period. Angiographic and computed axial tomographic studies of the brain demonstrated multiple large areas of infarction correlating with stenosis and occlusions of the internal carotid and posterior cerebral arteries. Moya moya-like findings were prominent radiographically. Results of angiographic, computed tomographic, and magnetic resonance imaging studies were interpreted as being compatible with large, medium, and small vessel disease, most likely a vasculitis. PMID- 1859481 TI - Treatment of refractory chronic Lyme arthritis with arthroscopic synovectomy. AB - Of 20 patients who underwent arthroscopic synovectomy for refractory chronic Lyme arthritis of the knee, 16 (80%) had resolution of joint inflammation during the first month after surgery or soon thereafter, and they have remained well during the 3-8-year followup period. Three of these 16 patients who were more disabled preoperatively, still had mild functional limitation at long-term followup. The remaining 4 patients (20%) had persistent or recurrent synovitis. We conclude that arthroscopic synovectomy is effective in treating chronic Lyme arthritis in patients in whom the disease does not respond to antibiotic therapy. PMID- 1859483 TI - C-reactive protein in rheumatology. PMID- 1859482 TI - Radiologic vignette. Amyloid arthropathy accompanying hemodialysis. PMID- 1859484 TI - All that glitters may be gold. PMID- 1859485 TI - Labial salivary gland lymphocytic infiltration in Sjogren's syndrome. PMID- 1859486 TI - Monozygotic twins concordant for Behcet's syndrome. PMID- 1859487 TI - Definition, incidence, and clinical description of flare in systemic lupus erythematosus. A prospective cohort study. AB - The course of systemic lupus erythematosus (SLE) is characterized by exacerbations (or flares) and remissions of disease activity. As part of an ongoing prospective cohort study, 3 disease activity indices, the physician's global assessment, the Lupus Activity Index, and the University of Toronto SLE Disease Activity Index, have been recorded, at least quarterly since 1987, on 185 SLE patients. We developed a definition of SLE flare and a description of its clinical epidemiology. Disease flare was defined as a change of greater than or equal to 1.0 in the physician's global assessment of disease activity (measured on a 0-3 scale) from the previous visit or from a visit within the last 93 days. Of the 185 patients, 98 (53%) had greater than or equal to 1 flare; the total number of flares was 146. The incidence of flare was 0.65 per patient-year of followup. The median time from the first study visit to a flare was 12 months. Flares were frequently characterized by constitutional symptoms, musculoskeletal involvement, cutaneous involvement, and decreasing levels of C3 and C4. At the time of flare, the mean University of Toronto SLE Disease Activity Index score increased by 3.0 and the mean Lupus Activity Index score (modified to omit the physician's global assessment) increased by 0.26. Overall, 44.8% of the flares prompted a change in treatment. Patients who experienced flares fulfilled more of the SLE criteria at entry and had been followed up for a longer duration after entry into the study, compared with those who did not have flares.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859488 TI - Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. AB - The purpose of this study was to assess long-term preservation of renal function in 111 patients with systemic lupus erythematosus and active glomerulonephritis who participated in a randomized treatment trial. Four different drug treatment programs, each of which allowed the use of low-dose oral prednisone in addition to the study drug(s), were compared with a regimen consisting solely of high-dose oral prednisone. Patients randomized to receive intravenous cyclophosphamide, oral cyclophosphamide, or oral azathioprine plus cyclophosphamide had significantly better preservation of renal function than did patients who were randomized to receive prednisone only. Results in the azathioprine group did not differ from those in the prednisone-only group. Cyclophosphamide appears to have long-term benefit in the delay or prevention of end-stage renal disease in patients with lupus nephritis. PMID- 1859489 TI - The latex test revisited. Rheumatoid factor testing in 8,287 rheumatic disease patients. AB - Rheumatoid factor (RF) testing by latex fixation in 8,287 outpatients yielded a sensitivity of 81.6% and 78.0% at titers of 1:20 and 1:80, respectively, and a specificity against noninflammatory rheumatic disorders (NIRD) of 96.6% and 97.9% and against NIRD plus inflammatory disorders of 95.2% and 96.8%, respectively. The predictive value of a positive test result at the clinic prevalence rate for rheumatoid arthritis (RA) (16.4%) was approximately 80%, and was 70% at 10% prevalence and 10% at 1% prevalence. No associations of RF with age or sex were found in non-RA patients. RF titers increased minimally with age in RA patients and were higher in men than in women. This study suggests that latex testing is far more specific than has been believed and that the titer is not spuriously increased with age. PMID- 1859491 TI - Long-term colchicine treatment in children with familial Mediterranean fever. AB - Three hundred fifty children (younger than age 16) who had familial Mediterranean fever (FMF) were given continuous prophylactic treatment with colchicine (1-2 mg/day) for 6-13 years. Complete remission of febrile attacks was achieved in 64% of the patients, and partial remission in 31%. Protracted attacks of arthritis virtually disappeared. None of the children developed amyloidosis while on the colchicine regimen. Side effects of colchicine were insignificant, and did not prompt permanent discontinuation of treatment in any of the children. Their growth, development, and subsequent fertility were normal. The efficacy of long term colchicine treatment of children with FMF makes early diagnosis life saving. PMID- 1859490 TI - Methotrexate versus azathioprine in the treatment of rheumatoid arthritis. A forty-eight-week randomized, double-blind trial. AB - We conducted a double-blind, randomized trial comparing azathioprine (AZA) and methotrexate (MTX) in the treatment of patients with rheumatoid arthritis in whom parenteral gold and/or D-penicillamine treatment had been unsuccessful. Patients were randomly assigned to receive either AZA (100 mg daily) or oral MTX (7.5 mg weekly). After 8 weeks, the dosage was increased depending on the clinical improvement. Sixty-four patients were followed up for 48 weeks (33 AZA, 31 MTX). Comparison of values at week 24 with baseline values revealed significant improvement in 12 of 13 disease variables in the MTX group and in 6 of 13 in the AZA group. Comparison between the 2 treatment groups at 24 weeks, by area-under the-curve analysis, showed significantly more improvement in the MTX group in terms of the swollen joint count, pain score, erythrocyte sedimentation rate, C reactive protein level, hemoglobin level, thrombocyte level, and disease activity score. A significant overall clinical improvement (disease activity score) was found in 7 of 20 patients treated with AZA and 18 of 30 patients treated with MTX after 24 weeks of therapy, and in 6 of 12 AZA-treated patients and 19 of 25 MTX treated patients after 48 weeks. The number of withdrawals due to side effects was significantly higher in the AZA group. After 48 weeks, only 12 patients from the AZA group (36%), but 25 from the MTX group (81%), were still using the initial drug. These results demonstrate MTX to be superior to AZA in the treatment of rheumatoid arthritis, with a more rapid clinical improvement which is sustained after 1 year, accompanied by a lower rate of serious adverse reactions. PMID- 1859492 TI - Endothelin, an endothelial-dependent vasoconstrictor in scleroderma. Enhanced production and profibrotic action. AB - The vascular endothelium is an important functional unit in the regulation of the vascular and perivascular environment. Various chemical and physical stimuli mediate an endothelial-dependent vasoconstriction through the release of endothelial soluble factors, such as the recently recognized endothelium-derived vasoconstrictor peptide called endothelin. The presence of circulating endothelin and the effect of cold exposure on plasma endothelin levels were investigated in patients with scleroderma and in healthy control subjects. Radioimmunoassay demonstrated a mean +/- SD plasma level of 10.7 +/- 7.3 pg/ml in the patients (n = 19) and 3.7 +/- 2 in the control subjects (n = 16) (P less than 0.005). These levels were also assessed in 5 control subjects and 5 scleroderma patients before and after 30 minutes of total body cooling (to 15 degrees C). The endothelin level did not change significantly in either group; however, 2 scleroderma patients showed a significant increase after cooling. The effects of endothelin on fibroblast proliferation and collagen synthesis were evaluated in order to assess the impact of released endothelin on the interstitium. A significant mitogenic effect and a collagen synthesis-enhancing effect, which were dose dependent, were seen. The strong, characteristically prolonged, vasoconstrictor activity coupled with the profibrotic effect demonstrated here make it likely that disturbances in the control of endothelin production can contribute to the pathogenesis of scleroderma. PMID- 1859494 TI - [Acute cerebral ischemia: pathogenesis and therapy. 24th Deidesheimer Lecture. 28/29 April 1990]. PMID- 1859493 TI - Occupation, income, and education as independent covariates of arthritis in four national probability samples. AB - The strong associations between education level and prevalence and severity of arthritis have recently been investigated, with some suggestion that the relationships might be causal. Data from 4 national probability samples were analyzed, in which occupation and income were measured currently and prior to the development of arthritis. These data indicate that previous studies overestimated the strength of the association between schooling and arthritis because income and, especially, occupation were not analyzed as separate covariates. The overestimate appears to be especially high for persons currently employed, for men, and for persons employed in dangerous jobs. Health policy strategies directed toward reducing arthritis rates require not simply a focus on education, but the additional socioeconomic status dimensions of income and occupational safety and health. PMID- 1859495 TI - [Acute cerebel ischemia: pathogenesis and therapy. Introduction to the theme]. PMID- 1859496 TI - Physiology of cerebral blood flow and metabolism. AB - At a normal blood flow and oxygen consumption, the brain uses exclusively glucose as metabolic substrate. Coupling between blood flow and metabolism takes place on a local level. This adjustment occurs in two different ways: 1. Short-term, dynamic coupling mediated by local vasoactive factors that ensure second-to second regulation. Such reactions appear to be partly dependent on the vascular endothelium. 2. Long-term, static coupling apparently mediated by capillary density and developed in response to local functional and metabolic activity. Recognizing these two mechanisms permits the distinction of apparent uncoupling during physiological conditions from real uncoupling during brain ischemia. PMID- 1859498 TI - [Studies of experimental cerebral ischemia with NMR spectroscopy]. AB - In vivo NMR (nuclear magnetic resonance) spectroscopy allows for non-invasive measurement of the intracellular pH and the concentration of different metabolites in defined areas of the brain. Phosphocreatine, ATP and lactic acid are of prime interest in ischaemia research. Moreover, a distinction can be made between glycolysis and the oxidative breakdown of glucose after administering C 13-labelled glucose. Finally, spectroscopy of fluorine-containing inert gases such as Freon-23 allows for measuring cerebral blood flow and for directly relating the metabolic alterations to the changes in cerebral blood flow. Given the non-invasive character of NMR spectroscopy all metabolic process occurring throughout one experiment can for the first time be followed up. Thus metabolic alterations during ischaemia can directly be correlated with post-ischaemic recovery processes. It has been shown with the cerebral ischaemia model in the cat that recovery after circulatory failure rather depends on post-ischaemic changes such as the recirculation rate or the speed of high-energy phosphate formation than on the speed of energy metabolism breakdown or acidosis occurring during ischaemia. The future of nuclear magnetic resonance spectroscopy in experimental ischaemia research certainly lies in the therapeutic range. As the exact extent of ischaemic damage can be determined in each experiment it is possible for the first time to define the effect of a drug substance on metabolic dysfunction in each individual experiment. This method is not only expected to reduce the number of laboratory animals but also to dramatically improve statistical variability compared to group comparisons. PMID- 1859497 TI - The biochemical basis of ischemic brain lesions. AB - A major mechanism leading to ischemic damage is loss of cellular ion homeostasis. Energy failure with shortage of ATP is responsible for presynaptic release of glutamate, which then triggers rapid cellular efflux of K+, and influx of Ca2+, Na+, and Cl-, with osmotically obligated water. The neuronal damage occurring in ischemia is probably secondary to the influx of Ca2+, and/or to the intracellular release of Ca2+, with the subsequent activation of proteases and lipases. A delayed form of ischemic damage, observed after transient ischemia, may be caused by increased calcium cycling across metabolically perturbed membranes. Another type of damage, typically leading to pan-necrosis (infarction), seems related to excessive acidosis and to production of free radicals. The mechanisms may involve release of pro-oxidant iron-catalyzed free radical reactions. It has been proposed that free radical damage may preferentially affect microvessels, predisposing to vasogenic edema. PMID- 1859499 TI - [Positron emission tomography for the determination of pathophysiology of cerebral ischemia]. AB - Positron emission tomography (PET) measurements of regional cerebral blood flow, blood volume, oxygen extraction, oxygen consumption and glucose consumption permit a detailed investigation of the pathophysiology of cerebral ischemia. The magnitude of the reduction of oxygen consumption appears generally as most important for tissue viability. In general, cerebral blood flow is severely reduced at the onset of an acute ischemic stroke. Subsequently, a very variable increase of cerebral blood flow may be found, often as "luxury perfusion" of irreversibly damaged tissue or relative hyperperfusion which is most frequently seen in the periphery of an ischemic infarct. Measurements of cerebral blood flow without measurement of oxygen metabolism are therefore of limited value. Glucose metabolism is less reduced than oxygen metabolism in most cases, indicating substantial anaerobic glycolysis. In few cases very high fluorodeoxyglucose uptake can be seen as an indicator of massive lactate production, which may cause additional toxic tissue damage. In cases of chronic or transient ischemias two stages of cerebral vascular decompensation can be distinguished by measurements of local blood volume, blood flow and oxygen consumption: the first stage is characterized by vasodilatation of peripheral vessels, resulting an increased ratio of cerebral blood volume to cerebral blood flow; the second stage is characterized by decreased blood flow and increased oxygen extraction. Ischemic brain lesions frequently cause alterations of blood flow and metabolism also in remote brain areas, apparently due to neuronal functional inactivation of incomplete ischemic damage. Global metabolic alterations correspond to the general clinical impairment of patients, whereas asymmetric focal deactivations correspond frequently to neuropsychological deficits. Studies of metabolic activation by functional stimulation appear promising as a tool to assess therapeutic strategies for rehabilitation. PMID- 1859500 TI - [Pharmacologic basis of therapy for cerebral ischemia]. AB - During the last 5 years neuroprotective effects of drugs have been intensively investigated. Various in vivo and in vitro models are available for testing neuroprotective actions of drugs. Calcium antagonists, glutamate antagonists, oxygen radical scavengers, 5-hydroxytryptamine-1A (5-HT1A) agonists and platelet activating factor (PAF) antagonists are experimentally well characterized as neuroprotectives and, thus, provide a basis for the development of clinically effective drugs. PMID- 1859502 TI - Intracellular calcium and pathophysiological changes in cerebral ischemia. AB - The role of calcium as a mediator in neuronal death during ischemia is now quite strong. Evidence supporting this link included studies in cell cultures, measurements of calcium accumulation in the mitochondria during ischemia as well as direct measurements of shifts in extracellular calcium using microelectrodes. Since high concentrations of intracellular free calcium have been hypothesized to lead to neuronal damage, direct in vivo measurements of this parameter in ischemia are important. The studies outlined demonstrate that changes in intracellular free calcium occur in focal ischemia and describe the time course of these changes. They indicate that cellular damage can be attenuated by the use of agents that block calcium channels (both voltage-sensitive and receptor operated) and support the concept that these agents owe their beneficial effects to their ability to reduce the accumulation of intracellular calcium. PMID- 1859501 TI - Neuroeffector functions of sensory nerve fibers in the cerebral circulation after global cerebral ischemia. AB - The importance of trigeminal neuroeffector mechanisms in the regulation of postischemic cerebral blood flow (CBF) was evaluated in cats subjected to chronic unilateral denervation of cortical sensory nerve fibers by trigeminal ganglionectomy or by the topical application of capsaicin to a cortical branch of the middle cerebral artery. CBF was determined using isotopically labeled microspheres before and at intervals after reperfusion following 10 min of global cerebral ischemia induced by four vessel occlusion combined with systemic hypotension. Postocclusive hyperemia 30 min after reperfusion in cortical gray matter ipsilateral to the side of denervation was attenuated by up to 58% (176 vs. 91 ml/100 g per min; p less than 0.05), but resting CBF, the duration of hyperemia, and the cerebrovascular response to hypercapnia were unaffected. These data underline the influence of neurogenic mechanisms in the regulation of postischemic CBF. Blockade of this axon reflex-like mechanism may reduce the morbidity associated with several hyperperfusion syndromes. PMID- 1859504 TI - Assessment of therapeutic effects in ischemic stroke. AB - The three fundamental methods of assessing the therapeutic effects in ischemic stroke are measurements of mortality, morbidity and quality of life. Increasingly more sophisticated cerebral blood flow and metabolism determinations are allowing insights into pathophysiology and giving guidance to the most promising therapeutic approaches. Experimental work and pathophysiological studies provide the scientific basis for therapy, but the assessments that ultimately matter to the patient are clinical, and preferably ones derived from controlled clinical trials. PMID- 1859503 TI - Calcium antagonists in the treatment of experimental cerebral ischemia. AB - Calcium ion functions widely as an intracellular messenger and regulator. Intracellular calcium dyshomeostasis occurs during hypoxic/ischemic cell injury, and pharmacological antagonism of calcium entry into neurons has been considered to be of potential therapeutic value. Calcium antagonists, in addition, tend to improve cerebral perfusion of both the normal and abnormal (post-ischemic) brain. Studies of these agents have shown variable degrees of cerebroprotection in focal and global ischemia models. (S)-Emopamil is a phenylalkylamine-type calcium channel blocker which also exhibits stereoselective antagonism of the serotonin S2 receptor and has excellent blood-brain barrier penetrability. Protection of hippocampal CA1 neurons has been demonstrated with pre-ischemic administration of (S)-emopamil in global ischemia models. Our laboratory has compared the efficacy of pre- vs. post-ischemic (S)-emopamil treatment on neuronal necrosis resulting from 10 min of transient normothermic global ischemia in the rat. (S)-Emopamil pre-treatment, 20 mg/kg i.p., 30 min prior to ischemia, with a second dose 2.5 h later, resulted in 1.8-2.4 fold increases in numbers of surviving CA1 pyramidal neurons. Post-ischemic administration was ineffective. Intracerebral microdialysis has revealed a partial attenuation of dopamine release with pre ischemic (S)-emopamil administration. In focal cerebral ischemia (middle cerebral artery occlusion in the rat), our laboratory has demonstrated a marked reduction in cortical infarct volume with (S)-emopamil pre- or post-treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859505 TI - Clinical trials in stroke prevention. AB - The randomized clinical trial has no satisfactory substitute in the evaluation of preventive treatment for stroke-threatened patients, and is the gold standard also in studies designed to test strategies which may reduce the impact of brain damage after ischemic stroke has occurred. Stroke data banks and contemporary non randomized comparisons are imperfect or flawed as bench-marks against which to judge treatments for these types of patients. Flaws in the design, execution and analysis of randomized clinical trials have been eliminated gradually over the past 35 years. On the basis of the existing trials in stroke prevention it may be stated that anticoagulants are effective in patients with non-rheumatic atrial fibrillation and after myocardial infarction. No other uses of anticoagulants in preventing ischemic stroke have been proven. Acetylsalicylic acid between 325 1300 mg/d will prevent stroke; lower doses have not been proven of value. Ticlopidine is effective. Benefit for dipyridamole, suloctidil or sulfinpyrazone has not been shown. Cerebral by-pass surgery has not been shown to have any role in stroke prevention in arteriosclerotic cerebral vascular disease. Carotid endarterectomy is still undergoing careful evaluation. PMID- 1859506 TI - Controlled clinical trials in stroke. AB - Reasons for the unsatisfactory number and reliability of most trials on the pharmacological treatment of acute cerebral ischemia are reviewed, focusing mainly on the clinical aspects of the issue. The opportunity of early intervention, supported by current pathophysiological hypotheses, is recognized. Past and recent Italian trials on ischemic stroke patients evaluated and treated within the first 6 h from onset are reported, also mentioning the results of a study including early cerebral angiography and SPECT (Single Photon Emission Computed Tomography). Early fibrinolytics associated to brain protecting agents are regarded as the future choice in clinical trials of acute cerebral ischemia. PMID- 1859507 TI - Local thrombolysis in the management of acute cerebral ischemia. AB - Local intraarterial fibrinolytic therapy (LIF) in patients with acute vertebrobasilar occlusion (AVBO) is a rational and, if successful, life saving treatment. The recent progress in this field is determined by the use of microcatheters for superselective basilar artery catheterisation and a "short time, high-dose" regimen using 750,000 IU urokinase in not more than 2 h. Two out of 7 patients died and 1 did not improve to a better than a locked-in-state. Four patients, however, survived with excellent outcome. PMID- 1859508 TI - Activation of rehabilitation. AB - Following the demonstration that catecholamine levels in the cerebral hemispheres were considerably reduced with stroke, efforts were made to change this situation in experimental animals. It was found that the use of amphetamine (CAS 300-62-9) greatly enhanced the recovery time of animals following experimental stroke, and that agents which block the release or function of catecholamines in the central nervous system seem to delay recovery. These observations have been used to determine whether or not the same conditions exist for humans with stroke. To date in one study there is evidence that use of amphetamine early after a stroke may enhance the rehabilitation process. The rehabilitation process can be impaired by a number of situations, the most common of which is depression. It has been shown that treatment of depression for patients with stroke in rehabilitation may improve the outcome as well as the speed of outcome. Prognosis for patients with stroke who enter rehabilitation programs is related to the degree of central nervous system damage. Those patients with only motor dysfunction tend to do much better in programs than those who have in addition sensory or visual disturbances. Usually maximum improvement of function following stroke and rehabilitation care occurs in the first three months. Carefully planned rehabilitation programs for patients following stroke with realistic goals can greatly improve the patients' function and enable them to remain as independent as possible. PMID- 1859509 TI - [Plasma and urine kinetics of amitriptyline oxide and its metabolites. Comparison of intravenous infusion and oral administration in volunteers]. AB - The study objective was to obtain detailed information on the plasma and urine kinetics of amitriptylinoxide (CAS 4317-14-0) and its metabolites. For this reason, 60 mg of amitriptylinoxide was administered to 12 subjects, both by intravenous infusion and by oral dosage, in a study performed according to a randomized two-way cross-over design. In plasma, we succeeded in analyzing the metabolites amitriptyline and nortriptyline in addition to the parent substance amitriptyloxide. The tests for the parent substance amitriptylinoxide revealed maximum plasma levels of 721 and 686 ng/ml at 1.96 h (i.v. infusion) and 0.82 h (oral formulation), respectively. Mean values of 2331 (infusion) and 1714 h.ng/ml (oral formulation) were determined for the area under the curve from time 0 to infinity AUC (0-infinity). We also produced a comprehensive evaluation of amitriptyline, however, this was not possible for the metabolite nortriptyline. In urine, we succeeded in a reliable quantification of 4 metabolites, namely cis OH-amitriptylinoxide, trans-OH-amitriptylinoxide, amitriptyline and OH nortriptyline, in addition to the parent substance amitriptylinoxide. In individual samples, nortriptyline, cis-OH-amitriptyline and trans-OH amitriptyline were additionally identified. In the course of the study, there were no reports or observations of any adverse reactions in addition to the side effects known for amitriptylinoxide from literature. There were no clinically relevant differences in tolerability observed between these two preparations. PMID- 1859510 TI - Pharmacokinetics of 3H-terguride in elderly volunteers. AB - Blood and plasma levels and excretion of labeled compounds and of the unchanged drug were measured after i.v. injection of 54 micrograms and p.o. administration of 540 micrograms of the ergoline derivative, terguride (CAS 37686-84-3), labeled with tritium, in 6 elderly male volunteers. Following i.v. injection plasma levels of terguride declined with a half-life of 0.5 h and those of radiolabeled compounds with half-lives of 0.5 h, 7 h and 19 h. The total clearance was 17 ml/min/kg and the volume of distribution was 0.7 l/kg. After p.o. administration terguride was rapidly and completely absorbed. The bioavailability was around 20%. Elimination of labeled compounds was complete within 7 days and proceeded mainly via the urine. Computer simulation of plasma levels after 4-times-a-day multiple administrations indicated slight accumulation of metabolites (factor 3) and no accumulation of terguride (factor 1). PMID- 1859511 TI - Effects of ouabain and digitoxin on the respiration of chick embryo cardiomyocytes in culture. AB - The effect of digitoxin (CAS 71-63-6) and ouabain (g-strophantin, CAS 630-60-4) on respiration, morphology and beating activity of cardiomyocytes in culture derived from embryonic chick hearts has been investigated. The drugs were applied in a perfusion system using a protein- and substrate-free perfusion medium (BSS) at two concentration of K+ (5.4 and 4 mmol/l). In either K+ concentration oxygen consumption was 0.13 +/- 0.05 nmol O2 h-1 per 1000 cells. During 3 h of perfusion with BSS oxygen consumption declines only slightly to 79 +/- 15% of the initial value. No relation was found between beating frequency and oxygen consumption. Increase in respiration ranged from 5 to 45% and lasted between 5 and 120 min. At concentrations being inhibitory to the Na+/K(+)-ATPase (greater than or equal to 1 mumol/l) ouabain stimulated respiration by about 20% at 4 mmol/l K+ and 10% at 5.4 mmol/l K+ while digitoxin was effective at 5.4 mmol/l only (a transient increase of 20%). At 0.1 nmol/l, (a concentration below the KD of the high affinity binding site of the Na+/K(+)-ATPase) ouabain caused a long lasting activation of respiration by about 30%, digitoxin induced a transient rise of up to 20% at 5.4 mmol/l K+. At 4 mmol/l K+ digitoxin did not affect respiration while ouabain caused a transient increase. The lowest concentration of ouabain inducing a reproducible activation of oxygen consumption was 0.1 pmol/l. At this concentration digitoxin was no longer effective. At 1 fmol/l respiration was stimulated only occasionally.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859512 TI - Biotransformation of nimodipine in rat, dog, and monkey. AB - 14C-labelled (+/-) 3-isopropyl5-(2-methoxyethyl)1,4-dihydro-2,6-dimethyl-4- (3 nitrophenyl)-pyridine-3,5-dicarboxylate (nimodipine, Bay e 9736, Nimotop; CAS 66085-59-4) was administered orally to rat, dog, and monkey (each 5, 10, or 20 mg/kg) and intraduodenally to rat (5 mg/kg). Urine was collected over a period of 24 h (bile 6 h). Dog bile was obtained from the gall bladder 4 h after oral dosing. Rat plasma was taken 1 h p. appl. of the unlabelled compound and additionally at different times following administration of [14C]nimodipine. The metabolite profiles in the excreta were established by TLC (radioscan/autoradiography). The unchanged drug was neither detectable in urine nor in bile, but was present in rat plasma. Nimodipine was extensively metabolized. 18 metabolites were isolated by LC, HPLC, and preparative TLC and identified by comparison with the reference substances using two-dimensional TLC, HPLC, GC/radio-GC, 1H-NMR-spectroscopy, MS, and GC/MS. About 75% of the renally excreted biotransformation products, more than 50% of the metabolites present in the bile (rat, dog) and approx. 80% of the plasma metabolites (rat only) have been identified. The large number of metabolites was produced by some common biotransformation reactions: dehydrogenation of the 1,4-dihydropyridine system, oxidative ester cleavage, oxidative O-demethylation and subsequent oxidation of the resulting primary alcohol to the carboxylic acid, hydroxylation of the methyl groups at 2- or 6-position, hydroxylation of one methyl group of the isopropyl ester moiety, reduction of the aromatic nitro group, and glucuronidation as phase II-reaction. PMID- 1859513 TI - [Pharmacokinetics of clonidine following intravenous administration of high doses for the treatment of delirium tremens]. AB - Concentrations of clonidine (CAS 4205-09-7. Catapresan) were measured in the plasma and the urine of 6 patients with delirium tremens who received 1.8-13.8 mg clonidine on the third treatment day. There was a linear correlation between the daily dose of clonidine and the steady state concentration of clonidine in the plasma, even with the high doses of clonidine used in this study. The total clonidine clearance was 29-62% lower than in normal volunteers. The renal clearance were 49-75% lower than normal. The renal excretion of the non metabolized clonidine was significantly lower than the normal range. The creatinine clearance on the other hand was only slightly reduced. The present study gives first hints that the metabolic clearance of clonidine in patients with delirium tremens is not decreased remarkably. PMID- 1859514 TI - Safety of ibopamine therapy in congestive heart failure. Ibopamine cohort study: baseline and 1-year results. AB - The study was designed to evaluate the safety of ibopamine (3,4-diisobutyryl ester of N-methyldopamine. SB(-)-505. Inopamil; CAS 66195-31-1) for the chronic treatment of congestive heart failure. It was conducted as a comparative cohort survey, versus digitalis. A third cohort was made with patients who received both drugs in association. Any differences between cohorts at baseline were dealt with by identifying explanatory variables with linear discriminant analysis and by performing multivariate statistical analysis by Cox's proportional hazard model. During 16 months, 3.330 patients were enrolled and then followed-up for a median time of 1 year. Baseline characteristics are reported as well as follow-up results on mortality, disease progression, anginal episodes, arrhythmias, need for cointervention and other undesired on-therapy events. Results pointing to efficacy are consistent with the favourable results from controlled randomized double blind medium--long term clinical trials. In addition, data from the present study do indeed provide strong evidence on the safety of long-term treatment with ibopamine. At variance with inotropic agents ibopamine did not increase mortality. The results rather suggest that long-term treatment with ibopamine affords an increase in survival and a delay in the progression of the disease, without adverse effects on cardiac rhythm and myocardial oxygen balance, and with a general improvement in the patients' quality of life. PMID- 1859515 TI - Decrease of fibrinogen in patients with peripheral atherosclerotic disease by ticlopidine. AB - Ticlopidine (Ticlodone: CAS 55142-85-3) is able to develop a positive effect on claudication in patients affected by peripheral atherosclerotic disease (PAD). It is also known that ticlopidine decreases fibrinogen levels in plasma. 15 PAD patients treated with ticlopidine for 3 months were studied, evaluating the drug's effect both on maximum walking distance and on fibrinogen. Plasma fibrinogen as coagulable protein, fibrinogen antigen (Partigen method), 125I fibrinogen survival, euglobulin lysis time and plasminogen were determined with the aim of clarifying if the decrease of plasma fibrinogen induced by ticlopidine is due to an increased destruction of a decreased production of the molecule. The normal levels of all tests before and after therapy both in ticlopidine treated patients and in the control group (acetylsalicylic acid + dipyridamol) indicate that the two hypotheses are not true. It is proposed that ticlopidine developing the known effect in decreasing the binding of fibrinogen to platelets induces a decrease only of activated fibrinogen. PMID- 1859516 TI - Pharmacokinetics of omeprazole in cirrhotic patients. AB - Omeprazole (CAS 73590-58-6), an H+, K+ ATPase inhibitor, is a potent suppressor of gastric acid secretion and a very active substance in the treatment of duodenal and gastric ulcers. The kinetic profile of omeprazole is well defined for healthy volunteers and for some high-risk population, but not so far for patients with liver disease. As the substance is mainly metabolized in the liver, changes in liver circulation and/or function might lead to changes in the pharmacokinetics of omeprazole. Aim of the study was to evaluate the kinetic profile in patients with liver disease and compare the results obtained in healthy volunteers, 16 subjects were included in the study: 8 patients with liver cirrhosis and 8 healthy volunteers. A single oral dose of omeprazole 20 mg was administered: plasma samples were collected for 24 h since omeprazole administration. The principal pharmacokinetic parameters were estimated for the two studied populations. PMID- 1859517 TI - Anti-inflammatory and immunomodulating effects of the novel agent gamma-(2 aminoethylamino)-2-butyrothienone. 1st communication: inhibitory effects on mouse paw edema. AB - A series of 4-hydroxy-(or-amino)-ethyl-amino butyrophenones or butyrothienones were synthesized. For detail studies on antiinflammatory effects, gamma-(2 aminoethylamino)-2-butyrothienone (gamma-ABT) was chosen as representative of these new non-steroidal anti-inflammatories (NSAID). The effect on mouse paw edema induced by various phlogistic agents was first investigated. The inhibitory effect of gamma-ABT on carrageenin-induced edema was remarkable and nearly equal to that of indometacin. Similarly to indometacin, gamma-ABT inhibited the early and late stage of yeast-induced edema in contrast to concanavalin A (Con A) induced edema which was only inhibited by gamma-ABT. Both the above induced edema are supposed to be unrelated to prostaglandins in the rat system. gamma-ABT displayed an inhibitory effect on nystatin-induced edema similar to indometacin suggesting that gamma-ABT has significant membrane stabilizing action and a strong blocking action on synthesis of prostaglandins. gamma-ABT inhibited as well the sustained edema induced by mustard. In conclusion gamma-ABT is an effective agent not only on acute but also on subacute and chronic inflammation and its mode of action appears similar to other NSAID. gamma-ABT posses in addition the advantage of antioxidant activity which is not shared by selective cyclooxygenase inhibitors and thus should be potentially effective in autoimmune diseases. PMID- 1859518 TI - Analgesic potency of a new anticonvulsant drug versus acetylsalicylic acid via laser somatosensory evoked potentials. Randomized placebo-controlled double-blind (5-way) crossover study. AB - A randomized, double-blind crossover study was performed with three different acute oral dosages of CM 40907 (3-(4-hydroxypiperidyl)-6-(2'-chlorophenyl) pyridazine) (600, 900 and 1200 mg), a newly developed anticonvulsant drug, vs acetylsalicylic acid (ASA, 1000 mg) and placebo in 12 male healthy volunteers to check analgesic potency. Objective algesimetry was done by Laser Somatosensory Evoked Potentials (LSEP). Subjective pain intensities were measured by retrospective visual analog scale ratings (VAS). Effects on objective vigilance were checked by Auditory Evoked Potentials (AEP). For both types of evoked potentials there was a simultaneous control of alterations in vigilance by means of the adaptive pursuit tracking task (APTT). A vigilance-controlled EEG (V-EEG) and a resting (R-EEG), visual analog scales (VAS) on sedation, excitation and anxiety as well as vital parameters (blood pressure and heart rate under supine and upright conditions) and adverse event scales were included in this trial as well. CM 40907 showed distinct analgesic effects on objective and subjective algesimetric parameters, which for the highest dosage (1200 mg) were superior in ("central") P2-amplitude suppression of LSEPs to those of ASA in ("peripheral") N1-amplitudes suppression and ongoing for more than 6 h. Subjective sedation was decreased, however, AEP-findings indicated a decreased vigilance after CM 40907. Some EEG-patterns, specifically related with CM 40907--although being ambiguous in classification terms--resembled features of benzodiazepines. Blood pressure and heart rate were raised in a clinically irrelevant manner. PMID- 1859519 TI - Escherichia coli bacteriuria and contraceptive method. AB - We evaluated the effects of contraceptive method on the occurrence of bacteriuria and vaginal colonization with Escherichia coli in 104 women who were evaluated prior to having sexual intercourse, the morning after intercourse, and 24 hours later. After intercourse, the prevalence of E coli bacteriuria increased slightly in oral contraceptive users but dramatically in both foam and condom users and diaphragm-spermicide users. Twenty-four hours later, the prevalence of bacteriuria remained significantly elevated only in the latter two groups. Similarly, vaginal colonization with E coli was more dramatic and persistent in users of diaphragm-spermicide and foam and condoms. Vaginal colonization with Candida species, enterococci, and staphylococci also increased significantly in diaphragm-spermicide users after intercourse. We conclude that use of the diaphragm with spermicidal jelly or use of a spermicidal foam with a condom markedly alters normal vaginal flora and strongly predisposes users to the development of vaginal colonization and bacteriuria with E coli. PMID- 1859520 TI - The validity of lecturer ratings by students and trained observers. AB - This study sought to determine to what degree student ratings of specific lecturer characteristics relate to trained observer ratings of such characteristics and to identify the distinguishing delivery characteristics of highly rated lecturers. The 15 lowest-rated lecturers and the 15 highest-rated lecturers, based on the mean ratings of students from two consecutive years (1982 and 1983) in a large multi-instructor course, served as the target group. Blinded non-student raters observed the lectures in 1984 (two per lecture) and completed quantitative and qualitative forms. For all six subscores from the quantitative form, statistically significant differences between the lecturers given the highest and lowest ratings were obtained. It is concluded that the students' ratings were stable across the three years; the independent observers discriminated between the lecturers the students rated the highest and the lowest; voice presentation characteristics discriminated the most effectively; and nonmedical non-student observers are potentially a useful source of information regarding faculty teaching skills. PMID- 1859521 TI - Monosialoganglioside in subarachnoid hemorrhage. AB - We studied 119 patients with disturbance of consciousness following subarachnoid hemorrhage, due mostly to verified aneurysm rupture, admitted to five Italian neurosurgical departments over 18 months. Level of consciousness as assessed by score on the Glasgow coma Scale ranged from 8 to 14 before the beginning of treatment; level of consciousness was assessed again 7, 14, and 21 days later. Patients were randomly allocated to treatment with monosialoganglioside or placebo according to a double-blind experimental design. The two treatment groups were homogeneous at entry with regard to the main clinical parameters. Both groups improved, but the rate and degree of improvement were greater in the monosialoganglioside-treated group. The difference was significant on days 14 (p = 0.04) and 21 (p = 0.02). Our results seem to confirm the hypothesis that monosialoganglioside reduces brain edema and provides nonspecific neuronal membrane protection. PMID- 1859522 TI - Ethics after Cartwright. PMID- 1859523 TI - 'Use of rubber dam in the UK'. PMID- 1859524 TI - Measuring health status: an approach for family practice researchers. AB - Research in family practice frequently involves the measurement of subjects' perceived health status. Those who are unfamiliar with this area may find the task difficult and frustrating. This paper offers an approach to the selection and assessment of measures of health status and specifically examines issues of feasibility, instrument content, appropriateness for subjects, instrument construction, reliability, validity, sensitivity to change, and measurement strategy. PMID- 1859525 TI - Laser treatment of a filtration bleb. PMID- 1859526 TI - The effects of sepsis and endotoxemia on gut glutamine metabolism. PMID- 1859527 TI - Synovial fistula of the knee: a complication of arthroscopy. AB - The occurrence of a synovial fistula after knee arthroscopy is uncommon. In a retrospective review of 976 arthroscopies of the knee over 3 years, six patients developed synovial fistulae (incidence 6.1/1,000). All patients were treated with short-term immobilization and oral prophylactic antibiotics. All fistulae closed after an average of 9 days of immobilization, and none required further treatment. Risk factors that may predispose a patient to fistula formation are posterior compartment portals and the presence of significant degenerative joint disease. A treatment protocol is presented. PMID- 1859528 TI - Maternal effect proteins. PMID- 1859529 TI - Oklahoma statute on donor oocytes. PMID- 1859530 TI - Geriatric consultation services: benefits and pitfalls. PMID- 1859531 TI - Carbamate formation and the neurotoxicity of L-alpha amino acids. PMID- 1859532 TI - Cardiac sources of cerebral embolism. PMID- 1859533 TI - Punch biopsy technique for the ophthalmologist. PMID- 1859534 TI - Loss of medicines with the licence review. PMID- 1859535 TI - Oral cancer: is it more common than cervical? AB - In Britain, mouth cancer is about half as common as cervical cancer, a significant level and one that deserves more attention than currently given by health care professionals, the media and the general public. If greater attention is called for in Britain, it is certainly needed worldwide. Oral/oropharyngeal cancer and cancer of the uterine cervix have comparable global averages and in some communities, oral/oropharyngeal cancer is actually more common. PMID- 1859537 TI - Management of ARDS. PMID- 1859536 TI - Drug interactions with methotrexate. PMID- 1859538 TI - Mediastinal pseudocyst associated with chronic pleural effusions. PMID- 1859539 TI - Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. PMID- 1859540 TI - Sudden sensorineural hearing loss and non-otological surgery. PMID- 1859541 TI - Hypoglycemia and focal neurologic deficits in diabetes mellitus. PMID- 1859542 TI - Diagnosis of scrapie. PMID- 1859543 TI - Pain relief in labour. Commentary. PMID- 1859544 TI - Axillary dissection in primary breast cancer. PMID- 1859545 TI - Spontaneous pneumothorax. PMID- 1859546 TI - Vitamins and IQ. PMID- 1859547 TI - Trials of homeopathy. PMID- 1859548 TI - Preoperative fasting: in medio stat virtus. PMID- 1859549 TI - Melatonin in health and disease. PMID- 1859550 TI - "Subjectively perceived quality of life". PMID- 1859551 TI - Pharmaceutical representatives. PMID- 1859552 TI - Segregation analysis of breast cancer: histopathologic data. PMID- 1859553 TI - Barrier-spermicide use and bacteriuria. PMID- 1859554 TI - Toothpaste-induced bronchospasm. PMID- 1859555 TI - Nasal mucosa grafting in ocular pemphigoid. PMID- 1859556 TI - The fallacy of the lacune hypothesis. PMID- 1859557 TI - The Level 1 Fluid Warmer. PMID- 1859558 TI - Clarifying confusion. PMID- 1859559 TI - Nuclear venography. PMID- 1859560 TI - Leadership in internal medicine; APM responds. PMID- 1859561 TI - Cervical necrotizing fasciitis: an uncommon sequela to dental infection. PMID- 1859562 TI - Continuous warm blood cardioplegia. PMID- 1859563 TI - Nocturnal cramps, quinine, and thrombocytopenia. PMID- 1859564 TI - Preventing fraud. PMID- 1859565 TI - Radiation workers and childhood leukaemia. PMID- 1859566 TI - Reporting of fine needle aspiration. PMID- 1859567 TI - Nasal continuous positive airway pressure. PMID- 1859568 TI - How idiopathic is idiopathic external hydrocephalus? PMID- 1859569 TI - Anorectal surgery in HIV-seropositive patients. PMID- 1859570 TI - Brown-Sequard and SLE. PMID- 1859571 TI - Rapp-Hodgkin ectodermal dysplasia. PMID- 1859572 TI - Rapp-Hodgkin syndrome. PMID- 1859573 TI - Dysbaric osteonecrosis. PMID- 1859574 TI - Thyroxine suppressive therapy of benign solitary thyroid nodules: some problems. PMID- 1859576 TI - [When to start orthodontic treatment]. AB - We are frequently ashed by patient and dentist what the best age is to begin orthodontic treatment. In this article we will try to classify what the best age to begin treatment is, according to the type of malocclusion. PMID- 1859575 TI - Selective DNA interaction of the novel distamycin derivative FCE 24517. AB - N-Deformyl-N-(4-N-N,N-bis(2-chloroethylamino)benzoyl)distamy cin A (FCE 24517) is a novel cytotoxic and antitumor agent shortly to be investigated in phase I clinical trials. It was equally effective in inhibiting the growth of the murine L1210 line and of a subline (L1210/PAM) resistant to nitrogen mustards, whereas distamycin A was virtually inactive. The cellular uptake and retention of FCE 24517 and distamycin A were similar, thus excluding the possibility that this marked variation in cytotoxic activity was due to different intracellular concentrations of the two compounds. FCE 24517 did not appear to act as an inhibitor of macromolecule synthesis. As shown by radioactively labeled precursor incorporation only 24 h after drug treatment a significant inhibition of DNA synthesis was observed in L1210 or in L1210/PAM, when a marked proportion of cells was arrested in premitotic phase. FCE 24517 did not cause DNA breaks, DNA interstrand cross-links, or DNA-protein cross-links in L1210 cells exposed to active drug concentrations. A very low amount of radioactivity was found to be bound irreversibly to DNA in L1210 cells exposed for 1 h to [14C]FCE 24517. Using plasmid pBr322 DNA fragments in a modified version of the Maxam and Gilbert DNA sequencing technique we found no detectable binding of FCE 24517 to N-7-guanine (the major site of alkylation for classical alkylating agents), whereas some alkylations to adenine (presumably to N-3-adenine) were demonstrated. Thus it appears that FCE 24517 is a novel antitumor agent with a mode of action different from that of the drugs currently used in the clinic. In summary it is suggested that FCE 24517 acts by causing a few selective alkylations to adenines in the minor groove of DNA, although the precise base sequence necessary has yet to be elucidated. PMID- 1859577 TI - [Electron microscopic study of a case of compound odontoma in an adolescent]. AB - We describe a case of compound odontome in a adolescent thirteen years old. The electronics microscopy reveale that the compound odontome is constituted for various dental formations which histologically composition is similar to the normal teeth. PMID- 1859578 TI - [Eruption anomalies: presentation of a case of retention]. AB - Dental retention is a cause of irregularities in the dental eruption. The retention of upper central incisors, although it is not very frequent, presents peculiar diagnostic and therapeutic aspects. We present a case of retention of a upper central incisor, due to a total inversion of said incisor. PMID- 1859579 TI - [Computer assisted orthodontic diagnosis]. AB - Quick Ceph is a program to help in orthodontic diagnosis, which is not limited to lateral cephalometric analysis but also allows, thanks to the Macintosh graphic interface the simulation of all orthodontic and surgical movements and so this to establish a treatment plan. PMID- 1859580 TI - [The pedodontist and dentinogenesis imperfecta]. AB - The purpose of this article is to present a treatment of dentinogenesis imperfecta in a 3 years old child. We reviewed some of the aspects to consider in the treatments of this alteration in primary dentition. PMID- 1859581 TI - [Absolute or relative isolation for fissure sealants? 12-month clinical study]. AB - The purpose of this clinical study is to analyse the effectiveness of a sealant. Rubber dam and cotton roll methods of isolation where compared with respect to the effect of isolation method on retreatment and protection from caries during 12 months. We study the cost effectiveness ratio for both methods of isolation. The results could not be substantiated any differences between two methods. PMID- 1859582 TI - [Osteogenesis imperfecta: presentation of a case]. AB - Osteogenesis Imperfecta constitutes a group of anomalies include between the lethal form of the disease and a condition in which the cortical bone is thiness and more breakable. It's frequently associated to dental abnormalities. It's possible to found serious bone alterations associated to regular dentition or on the contrary. The present article reports a clinical case with Osteogenesis Imperfecta Tarda. PMID- 1859583 TI - [Follicular cyst. Apropos of a case]. AB - When there's a diagnosis of follicular cyst. In front of lesions of advanced decay in deciduoud teeth about which is possible to presume chronical apical infection, we have to evaluate carefully the choice of treatment: pulpectomy or exodontia and the placement of a space maintainer. In this article there's a case in which a non-indicated pulpectomy was practised and caused a follicular cyst which is a menace to the formation and position of the unerupted permanent teeth. After the surgery we proceeded to exodontia and subsequently to place a space maintainer. PMID- 1859584 TI - [Nursing caries. Therapeutic needs]. AB - The purpose of the study was to investigate a pattern of caries in preschool children, associated with a history of frequent drinking of fruit juices or sugered milk, into the feeding bottle, often given at bedtime. The rampant caries which are produced affect all maxillary primary incisors and the first primary molars, the canines and the second primary molars are less affected and the mandibular primary incisors never are affected. The treatment needs have been determinated. The extractions, the obturations, pulpotomy and stainless steel crown together with infant denture, this therapeutic ways have been utilized. PMID- 1859586 TI - [Approach to esthetic dentistry]. PMID- 1859585 TI - [Chronology and sequence of tooth eruption. A review of the literature]. PMID- 1859587 TI - Pharmacomodulation of 7-(2-methylene-butyryl)-2,3-dihydrobenzoxazin-[1,4]-3-one structure and normolipemic activity. AB - A series of compounds from 7-(2-methylene butyryl)-2,3-dihydro benzoxazin-[1,4]-3 one was synthesized and evaluated for its lipid lowering action in animal models. Substitutions in positions 2, 4 and 7 were performed. The results of the structure-activity relationships are very difficult to be interpreted. The different modifications tested did not show any improvement in the normolipemic activity. PMID- 1859588 TI - Synthesis and antihypertensive activity of some 2-aminobenzimidazole and indole derivatives. AB - The synthesis of some 2-aminobenzimidazole and indole amide derivatives containing a 2,6-dichloroaniline moiety is described. The preparation of a theophylline derivative is also reported. All the compounds tested showed no appreciable antihypertensive activity on spontaneously hypertensive rats. PMID- 1859590 TI - Synthesis and anti human immune virus activity of some new fluorine containing substituted -3-thioxo-1,2,4-triazin-5-ones. AB - Some new fluorine containing substituted 3-thioxo-1,2,4-triazin-5-ones (2-17) have been synthesized and evaluated for in vitro anti human immune virus (HIV) activity. Most of the new compounds displayed a lethal activity, while compounds 2, 6, 7, 10, 11 and 14 displayed a significant antiviral activity. The structures are supported by elemental analysis, IR, UV and 1H-NMR spectral data. PMID- 1859589 TI - Formamidines with antinociceptive and antiinflammatory activities. AB - Pursuing our investigations on 7-amino-2,3-polymethyleneindole derivatives, a set of 7-(dimethylaminomethylene)-amino-2,3-polymethyleneindoles, together with some other aryl or cycloalkyl substituted formamidines, were prepared and tested for analgesic and antiinflammatory activities. Several compounds resulted endowed with one or both of these activities; the indole derivatives 1 and 2 exhibited a good degree of both of them. PMID- 1859592 TI - Community participation in research and action against alcoholism. AB - An epidemiological study of sickle cell disease in the Gadchiroli district of India established it as a major problem but resulted in no public initiative or action. In contrast, research and action against alcoholism using the participatory approach resulted in massive community participation and proved highly successful. Public health programmes need community participation, yet most research in this field is self-defeating because it alienates lay people. PMID- 1859593 TI - Meeting the pharmaceutical needs of a developing country. AB - Zimbabwe is making advances in the selection, procurement, distribution, storage, management and use of pharmaceutical products. The periodic updating of the country's essential drugs list is a vital part of this process. PMID- 1859591 TI - Safe motherhood: a challenge to midwifery practice. AB - The principal way of achieving maternal health and safe motherhood is to expand the specific functions and/or categories of midwifery personnel. This includes strengthening knowledge and skills to improve the quality and quantity of care. Success would ensure that for millions of women the prospect of childbirth would be one of joy rather than misery. PMID- 1859595 TI - Drugs: towards sound prescribing and pricing. AB - In Mali, uninformed self-medication is widespread, much prescribing is faulty, drug prices are often too high, and the distribution of drugs leaves much to be desired. It is expected that, through a new procurement policy, the situation will improve. PMID- 1859594 TI - Drug information for patients in the community. AB - The failure of patients to follow drug regimens may be due to lack of information or the negative attitudes of patients and health care providers. We have found that most patients in rural areas did not ask for information about their treatment because they felt their health carers had little time for such matters. These problems will continue unless practitioners at all levels make better efforts to understand their patients' perceptions of illness and treatment, and especially whether compliance with drug treatment is feasible. PMID- 1859596 TI - Feeling unwell? Must you go straight to hospital? AB - If people ignore the primary level and go directly to hospital when they are ill the health care system becomes overburdened at the higher levels, inefficient, and unjustifiably expensive. The most effective way to persuade people to use the first level of care is to ensure that its services are reliable and its facilities are attractive as those of the referral levels. Financial incentives aimed at encouraging respect for the system can also play a part. PMID- 1859597 TI - Self-reliance in health among village women. PMID- 1859598 TI - American medical students broaden their horizons in the Third World. AB - Every year for several decades some American medical students have been visiting Third World countries in order to participate in the practices there. These experiences have proved invaluable in helping them to work in the USA among minorities having unorthodox views on health and disease. PMID- 1859599 TI - Training primary health care workers to foster community participation. AB - A low level of community participation was identified as one of the weaknesses of the health sector in the United Republic of Tanzania. In order to remedy this situation, a systematic process of training trainers and students was established with full involvement of village people. Twenty-five themes were put forward as starting points for discussions between students and villagers. The students were encouraged to learn from the villagers by listening to them and asking them questions. They also participated in community activities and lived with villagers so as to obtain a good understanding of rural living conditions. In this way, problems were identified and solutions were jointly formulated. A workbook was developed during a series of workshops with students, trainers, village communities, and planners. At least two teachers were trained from each health training school; all schools were supplied with workbooks. The approach has been adopted by most health training schools in Tanzania, and the Ministry of Health is now committed to it. Both students and trainers find this to be a valuable learning experience. PMID- 1859601 TI - One disease, one name. PMID- 1859602 TI - Implications of the tobacco dependence syndrome for smoking control programmes. AB - Motivational and psychosocial treatments for tobacco dependence, while valuable, are not sufficient to solve nicotine-related problems, which usually require a pharmacological approach. There is also a need for training programmes for health workers and major educational campaigns on the nature of tobacco dependence to be directed at opinion leaders, teachers and the public at large. PMID- 1859600 TI - A partnership in epidemiological research. AB - Four medical research teams completed ten epidemiological investigations in Djibouti and thus provided the country's Ministry of Health with valuable information on infectious disease risks. A major factor contributing to the success of the work was the high degree of cooperation between the Ministry, a United States naval medical research unit, and the World Health Organization as coordinator. PMID- 1859603 TI - The index technique for rapid assessment of district health situations. PMID- 1859604 TI - Competition for promoting family health. PMID- 1859605 TI - Determining the respiratory rate in children. PMID- 1859606 TI - Social attitudes and family planning in rural Kenya. PMID- 1859607 TI - A smoking cessation campaign in a Norwegian newspaper. PMID- 1859608 TI - Much blindness is avoidable. AB - The main strategy of the World Health Organization's Programme for the Prevention of Blindness is to make simple eye care available to all populations. In many countries, national committees are responsible for the optimal utilization of resources and the coordination of work in this field. Several major international nongovernmental organizations provide support. Factors limiting the effectiveness of national programmes are being addressed in WHO collaborating centres. PMID- 1859609 TI - Health programme planning for consolidation and quality. AB - Botswana's Ministry of Health is implementing a new approach to resource planning and management whereby the work of planners and technical experts is integrated with that of managers of programmes and facilities. The aim is to help the managers to make better use of resources in service delivery. PMID- 1859610 TI - Decentralizing health services in Australia. AB - During the past 15 years the district health services in some parts of Australia have been reorganized, with the development of coordinated programmes that provide services across hospital and community boundaries as well as continuity of care over prolonged periods. Some financial resources have been redirected from institutions to community-based services. The process has been so successful that district reorganization has now been implemented throughout New South Wales (population, 5.5 million) and elsewhere in Australia. PMID- 1859611 TI - World trends in alcohol consumption. AB - Data from a worldwide alcohol project suggest significant changes in world alcohol consumption since the early 1970s, with many developing countries showing large increases up to 1981. Whether the recent declines in consumption observed in developed countries will be mirrored in the developing world remains to be seen. PMID- 1859612 TI - In search of a simulator. PMID- 1859613 TI - Demonstration of lateral patellar subluxation: the 30 degrees LR projection lateral rotation. PMID- 1859614 TI - Methods for the removal of a single layer of photographic emulsion from duplitised x-ray film. PMID- 1859615 TI - Scattered radiation and the lateral lumbar spine. PMID- 1859616 TI - Evidence against a specific effect of cholinergic drugs on spatial memory in primates. AB - A scopolamine-like delay-dependent impairment in spatial delayed response performance in rhesus monkeys was induced by irrelevant interpolated activity or by using extended retention intervals. Physostigmine readily reversed the effects of scopolamine but had no effect on performance in young monkeys performing an irrelevant distractor task or in monkeys tested using extended retention intervals. Reducing stimulus control did not impair performance and did not alter the dose-response curve for induction of a deficit by scopolamine. Reducing the stimulus presentation time impaired performance across all retention intervals in a way which did not resemble the effect of scopolamine and which disappeared with practice. Our findings do not support the proposal that physostigmine interacts specifically with short-term spatial memory in primates. PMID- 1859617 TI - Effects of unilateral thalamic lesion upon interocular transfer of visual discrimination in pigeons. II: Lesion in the untrained hemisphere (sensory deficits). AB - In a previous study, rotundal lesions in the 'trained' hemisphere caused deficits in interocular transfer of visual discrimination when the lesion was made after acquisition of the monocular learning, but not when the lesion was made before the monocular learning. In the present study, a rotundal lesion was made in the 'untrained' hemisphere before and after monocular training. The lesion caused deficits in transfer regardless of the temporal relation between the lesion and the training. Such deficits are likely to be 'sensory deficits' since visual information from the eye goes to the damaged rotundus when tested with the untrained eye. The relation between the 'sensory' versus 'mnemonic' deficits from damage to nucleus rotundus in the trained hemisphere are discussed. PMID- 1859618 TI - Synchronisation of tongue and forepaw movements in the rat: a model of instrumental muscle synergy. AB - Acquisition of new skills is often implemented by the formation of coordinated movements of functionally unrelated muscles. This situation was modelled in rats trained to lick at a retractable spout which was automatically withdrawn after termination of every lick but could be returned by pressing and releasing a lever placed 4 cm below the spout. Rats (n = 12) learned to perform short presses (50 ms) synchronized with the lick cycle in a way allowing continuous drinking. When the distance of the lever from the box was increased from 5 mm to 12.5 mm or when the force required for lever operation was raised from 20 g to 90 g, the lick press interval increased in multiples of the interlick interval. Licking ceased during the lever pressing but regular timing of subsequent licks indicated uninterrupted activity of the licking generator. It is concluded that the coordination of orofacial and forelimb muscles engaged in licking and lever pressing, respectively, is accomplished by propagation of the activity of the lick generator to cortical and subcortical motor centers. PMID- 1859619 TI - Single-unit activity in the dorsomedial prefrontal cortex during the expression of discriminative bradycardia in rabbits. AB - Much recent evidence suggests that the medial prefrontal cortex (PFCm) participates in the development and/or expression of learned, primary bradycardiac adjustments in rabbits. Accordingly, the present experiments were undertaken to determine whether single-unit activity in the precentral agranular and anterior cingulate regions of the PFCm is systematically affected by differential aversive Pavlovian conditioning and, if so, whether such activity is correlated with concomitant heart rate (HR) variables. In these studies, extracellular recordings were made during a training procedure that involved two distinctive, tone conditioned stimuli (CSs); one of these (CS+) was often paired with eye-shock (unconditioned stimulus, US), whereas the other (CS-) was never so paired. Of the 100 spontaneously-active cells whose activity was so evaluated, 74 were found to be tone-responsive and could be classified as belonging to one of 5 subpopulations on the basis of their specific patterns of evoked changes in discharge; additional data suggested that these cells were also generally responsive to the eye-shock US. Regarding the effects of training, the vast majority of cells in these subpopulations showed greater evoked activity changes on CS+, as opposed to CS-, trials, irrespective of the sign (i.e. increase and/or decrease) of their responses. This finding was not confounded by differences in baseline activity preceding CS+ vs CS- trials, which was generally characterized as being both irregular and unrelated to concomitant HR variables; nor could it be attributed to unconditioned responses biases. Thus, the discriminative activity patterns of these cells appeared to reflect the differential Pavlovian contingencies in effect. Moreover, approximately half of these cells exhibited tone-evoked activity changes that were reliably correlated with concomitant HR changes on a trial-by-trial basis. Consequently, the present data indicate that training-induced changes in the CS-evoked activity of PFCm cells are significantly related to aversively conditioned bradycardia in rabbits. PMID- 1859620 TI - Enhanced recovery of learned alternation in ganglioside-treated rats after unilateral entorhinal lesions. AB - The present study demonstrates that an abbreviated regimen of ganglioside treatments attenuates the behavioral impairments produced by unilateral lesions of the entorhinal cortex. Ganglioside treatments not only accelerate recovery of learned alternation on a Y-maze, but also reduce total errors and perseverative errors. PMID- 1859622 TI - [Photography in dentistry]. PMID- 1859621 TI - [A new natural collagen hemostatic sponge]. PMID- 1859623 TI - [Cerasand ceramic implants]. PMID- 1859624 TI - [Statistical methodology in the dental field]. PMID- 1859625 TI - [Preparation for ceramic veneers]. PMID- 1859626 TI - Purification and characterization of two types of Cytisus sessilifolius anti-H(O) lectins by affinity chromatography. AB - Two anti-H(O) lectins were separated from extracts of Cytisus sessilifolius seeds by successive affinity chromatographies on columns of di-N-acetylchitobiose- and galactose-Sepharose 4B. One was found to be inhibited most by di-N acetylchitotriose or tri-N-acetylchitotriose [Cytisus-type anti-H(O) lectin designated as Cytisus sessilifolius lectin I (CSA-I)] and the other anti-H(O) lectin was inhibited by galactose or lactose and designated as Cytisus sessilifolius lectin II (CSA-II). These two anti-H(O) lectins were further purified by gel filtration on TSK-Gel G3000SW. These preparations were homogeneous as judged by polyacrylamide gel electrophoresis and gel filtration. The molecular masses of the purified lectins I and II were found to be 95,000 and 68,000 Da, respectively, by gel filtration on TSK-Gel G3000SW. On polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and 2 mercaptoethanol, both lectins gave a single component of molecular masses of 27,000 +/- 2,000 and 34,000 +/- 2,000 Da, respectively, suggesting that the lectins I and II were composed of four and two apparently identical subunits, respectively. Lectins I and II contain 38% and 13% carbohydrate, respectively, and only very small amounts of cysteine and methionine, but they are rich in aspartic acid, serine and glycine. The N-terminal amino-acid sequences of these two lectins were determined and compared with those of several lectins already published. PMID- 1859627 TI - Protein structure and cDNA nucleotide sequence of the Japanese quail alpha A globin. AB - The primary structure of the alpha polypeptide chain (alpha A) of the major component (QII) of Japanese quail hemoglobin was determined by protein and cDNA sequence analysis. The amino-acid sequences of all the soluble tryptic peptides were determined by the conventional protein sequencing technology. The sequence of the remaining portion, which contained an insoluble "core region", was determined through determination of the cDNA nucleotide sequence. The cDNA clones coding for the alpha A globin were isolated from the quail reticulocyte cDNA library, mapped by restriction enzyme digestion, and the nucleotide sequence was determined completely. The primary structure of quail alpha A globin shows a close similarity to that of chicken alpha A globin. PMID- 1859628 TI - Determination of the molecular structure of the human free secretory component. AB - Here, we present the experimental data, leading to determination of the primary structure, the linkage of the carbohydrates and the arrangements of the disulfide bonds of the human free secretory component. Methods of protein chemistry were used. The protein can be divided into five homology regions and is a member of the immunoglobulin superfamily. PMID- 1859629 TI - Difference in polyamine transport in human B and T lymphocytes. AB - Preparations enriched in human blood B lymphocytes are able to take up polyamines efficiently. Uptake by T cells is barely detectable. Human non-circulating B cells (from tonsils) have a much lower ability to take up polyamines, as do mixed populations of bovine lymph nodes. B cells contain a higher amount of endogenous polyamines and show higher ornithine decarboxylase activity than T cells. PMID- 1859630 TI - Enhancement of ouabain and calcium ionophore A23187 of outward transport of polyamines from lymphocytes. AB - Human lymphocytes in culture loaded with radioactive polyamines slowly release radioactivity into the medium. N1-Acetylspermidine is mostly released from spermidine and spermine. Both ouabain and calcium ionophore A23187 increase the outward transport, but by different mechanisms. Ouabain inhibits the acetylation of spermidine, and free spermidine is released, whereas A23187 increases both acetylation of spermidine and the efflux of N1-acetylspermidine. PMID- 1859631 TI - Bacterial pyruvate kinases have a shorter N-terminal domain. AB - The N-terminal portions of the two forms of pyruvate kinase (EC2.7.1.40) from Escherichia coli have been sequenced up the 48th and 43rd residue, respectively. Comparison with the known primary structures shows that bacterial enzymes lack a substantial portion of the N-terminal sequence with respect to pyruvate kinases from vertebrates. This makes the suggested functional role of the N-terminal domain unlikely [Muirhead, H. (1990) Biochem. Soc. Trans. 18, 193-196] although an elongation of this domain with evolution is apparent. PMID- 1859632 TI - Purification and characterization of a new type lactose-binding Ulex europaeus lectin by affinity chromatography. AB - A new type lactose-binding lectin was purified from extracts of Ulex europaeus seeds by affinity chromatography on a column of galactose-Sepharose 4B, followed by gel filtration on Sephacryl S-300. This lectin, designated as Ulex europaeus lectin III (UEA-III), was found to be inhibited by lactose. The dimeric lectin is a glycoprotein with a molecular mass of 70,000 Da; it consists of two apparently identical subunits of a molecular mass of 34,000 Da. Compositional analysis showed that this lectin contains 30% carbohydrate and a large amount of aspartic acid, serine and valine, but no sulfur-containing amino acids. The N-terminal amino-acid sequences of L-fucose-binding Ulex europaeus lectin I (UEA-I) and di-N acetylchitobiose-binding Ulex europaeus lectin II (UEA-II), both of which we have already purified and characterized, and that of UEA-III were determined and compared. PMID- 1859635 TI - Prevention is better than cure. PMID- 1859634 TI - A remit to care. PMID- 1859633 TI - The company of strangers. PMID- 1859636 TI - A positive force. PMID- 1859637 TI - A peaceful death. PMID- 1859638 TI - Questions of quality. PMID- 1859640 TI - Taking a break. PMID- 1859639 TI - Instructive exercise. PMID- 1859641 TI - Testing times. PMID- 1859642 TI - Voting rights. PMID- 1859643 TI - Helicobacter pylori and associated gastroduodenal diseases. Review article. AB - Helicobacter pylori is a microaerophilic, Gram-negative, spiral rod, the role of which in different gastric diseases has been investigated worldwide since the beginning of the 1980s. H. pylori has been shown to be the causative agent in active chronic gastritis, and it is regularly found in patients endoscopied for duodenal ulcer. The bacterium is also frequently isolated from persons with gastric ulcer, gastric carcinoma and non-ulcer dyspepsia. Apart from cultivation of the bacterium, other diagnostic procedures include various staining methods and urease tests of gastric biopsy samples. The application of non-invasive diagnostic methods, serology and urea breath tests, is rapidly increasing. H. pylori is susceptible to several antimicrobials in vitro, but eradication of the bacterium from the gastric mucosa is not always achieved. The best results until now have been obtained with the combined use of bismuth salts and two antibiotics. In active chronic gastritis and duodenal ulcer patients, eradication of the bacteria has resulted in healing of the disease with permanent decrease of circulating antibodies and negative urease tests. H. pylori has been found worldwide and the infection shows an age-dependent increase. Man, apparently, is the reservoir of the bacterium, but the exact mechanisms of interhuman transmission are still not defined. PMID- 1859644 TI - Susceptibility testing of anaerobic bacteria. Regression lines for six antibiotics determined with and without prediffusion. AB - The relationship between susceptibility testing by an agar dilution test and a tablet diffusion test was studied for 60 anaerobic bacteria (20 B. fragilis, 20 anaerobic cocci, 20 Clostridium species). For cefoxitin, no prediffusion and prediffusion times of one h, three h, 12 h, 24 h and 48 h were examined. For metronidazole, erythromycin, clindamycin, penicillin and imipenem, only 24 h prediffusion and no prediffusion were studied. Measurements were made after incubation for 24 h and 48 h. Prediffusion improved the correlation for all antibiotics tested, and 24 h prediffusion gave the best results. The slope of the regression line increased and the influence of the individual growth parameters on zone size was reduced. Prediction of susceptibility based on three zone breakpoints to estimate MIC was also better with 24 h prediffusion. However, the variation about the regression line for many of the antibiotics was still extremely high. Measurements after 24 h and 48 h incubation times showed almost identical regression equations, except for erythromycin, where the regression lines differed. PMID- 1859646 TI - Antibiosis between bacteria isolated from the vagina of women with and without signs of bacterial vaginosis. AB - Lactobacilli from women with and without bacterial vaginosis (BV) were tested for H2O2 production. Thirty-seven (79%) of the 47 strains of lactobacilli isolated from the women without BV produced H2O2, while only nine (23%) of the 39 strains of lactobacilli obtained from women with BV did so. Five of 20 H2O2-producing and two of 26 non-producing strains of Lactobacillus exhibited antibiosis against four of 12 strains of peptostreptococci and two of 10 strains of Mobiluncus spp. None of a further 41 different anaerobic and facultative anaerobic bacterial strains were inhibited by any of the isolates of lactobacilli tested. Some strains of Gardnerella vaginalis, Bacteriodes spp., Mobiluncus spp. and Peptostreptococcus spp. inhibited the growth of three strains of lactobacilli belonging to different species. When the pH of the culture medium was increased from 6.0 to 6.5 this led to a decrease in the number of strains inhibited and/or the size of the growth-inhibitory zones. Different concentrations of H2O2 did not inhibit any of the strains tested. The growth-inhibitory effect of lactobacilli could not be related to their bacteriocin production. Increasing the iron content of the medium by adding FeCl3 (0.01 mM-1 mM) decreased or completely abolished the antibiosis. PMID- 1859647 TI - Prognostic implications of image cytometric assessments of nuclear DNA distribution pattern of neoplastic cells in thyroid medullary carcinoma. A retrospective study using disaggregated, formalin-fixed, paraffin-embedded specimens. AB - A modified technique for cytometric analysis of the nuclear DNA distribution pattern of neoplastic cells has been applied on archival histopathological specimens originating from 42 patients who had undergone thyroidectomy for medullary carcinoma of the thyroid gland. Five of the cases were of familial type. The DNA cytometric assessments were made by means of computerized image analysis techniques on Feulgen-stained, intact, cytodiagnostically identified neoplastic nuclei obtained from histopathologically selected areas of paraffin blocks. The nuclei were enriched by means of a cytospin technique after deparaffinization of pronase-induced disaggregation of 50 microns thick sections. Only seven of the tumours were found to consist of neoplastic cells where the nuclei showed a DNA distribution pattern of "aneuploid" type; six of these patients had a rapidly progressive neoplastic disease, but the seventh patient did not. Among all the patients whose tumour cell nuclei showed a cytometric DNA ploidy pattern of "euploid" type, not less than about half had a rapidly progressive neoplastic disease. Thus, even when a refined cytometric technique is used, the value of the nuclear DNA ploidy pattern of the neoplastic cells as a prognostic variable in MTC is limited. PMID- 1859645 TI - Antimicrobial resistance of enteropathogenic Escherichia coli strains from a nosocomial outbreak in Kenya. AB - The majority of the 78 enteropathogenic (EPEC) and the 151 non-EPEC Escherichia coli strains isolated from preterm neonates during an outbreak of gastroenteritis in a hospital in Nairobi, Kenya, were resistant to trimethoprim-sulfamethoxaxole, chloramphenicol, oxytetracycline and ampicillin, but only a few strains were resistant to cefazolin, cefamandole, cefotaxime, amikacin and nalidixic acid. Fourteen different antimicrobial resistance patterns were observed in the 229 strains of E. coli analysed. Eighty-two percent of the EPEC strains belonged to two resistance pattern compared with 79% of non-EPEC strains which exhibited three resistance patterns. There was no consistent relationship between plasmid profile group and antimicrobial resistance pattern, although one resistance pattern was more frequently observed in EAF-positive strains belonging to the dominant plasmid profile group. Nine percent of the EPEC strains were resistant to gentamicin compared to 37% in the non-EPEC group. No correlation was observed between administration of gentamicin and percentage of resistant strains isolated. None of the nine neonates receiving gentamicin died during the outbreak. Gentamicin resistance was observed in E. coli strains from six out of these nine neonates. Five out of fourteen neonates who received other antimicrobials, or no antibiotic treatment at all, died. PMID- 1859648 TI - Interleukin-2 stimulation of blood mononuclear cells from patients with inflammatory bowel disease. AB - The functional capacity of biologically active, high-affinity interleukin-2 receptors (IL-2R) was studied by means of interleukin-2 (IL-2) stimulation of blood mononuclear cells (BMC) from 22 patients with inflammatory bowel disease (IBD) and 24 controls. The spontaneous, as well as the IL-2-induced, proliferative responses were significantly decreased in patients with active IBD, whereas the expressions of biologically inactive, low-affinity IL-2R (i.e. TAC antigen or CD25) were significantly increased in the same BMC cultures. In contrast, no significant differences were seen between patients and controls when BMC were stimulated with a nonspecific mitogen (phytohemagglutinin). The results suggest that a downregulation of IL-2 responsiveness may contribute to decreased BMC proliferation in vitro in active IBD. PMID- 1859649 TI - Central nervous system calcifications following tap water rinsing in autopsy material from children. A pitfall. AB - CNS from 80 children collected consecutively at the Institute of Forensic Medicine, Aarhus, were investigated. Owing to peculiar calcifications of the first 41 CNS examined, we gradually came to suspect that some external factors had influenced the results. Different fixation methods used on the CNS, rinsed or not rinsed in tap water, led us to suggest that the relatively high calcium content in the tap water in our part of the country was the cause. The non pathologic calcification could presumably mimic metabolic diseases. PMID- 1859650 TI - Beneficial effects of intranasal applications of capsaicin in patients with vasomotor rhinitis. AB - Capsaicin, a nonenamide derived from Capsicum plants, has proven useful in patients with vasomotor rhinitis. In the present study, we studied the effects of 15 micrograms capsaicin suspended in 100 microliters solution in patients with known vasomotor rhinitis. Drug was given 3 times/day for 3 days to each patient by means of a spray delivered to the nasal mucosa. Acute effects induced by the drug included painful sensation and secretion of nasal fluid but were no longer observed at the last capsaicin application. Patients recorded their symptoms over a 1-month period. The mean symptom score involving nasal obstruction and nasal secretion was markedly reduced by capsaicin treatment. We advance the hypothesis that the beneficial effect of drug treatment may be due to its specific action on the peripheral endings of primary sensory neurons leading to their functional blockade. Further randomized, double-blind, placebo-controlled trial is now needed. PMID- 1859651 TI - Gentamicin-induced alterations of succinic dehydrogenase activity in the organ of Corti as revealed by non-decalcified frozen sections of the guinea pig's cochlea. AB - The distribution of succinic dehydrogenase (SDH) activity and the changes of SDH activity after injection of gentamicin (GM) were observed in the organ of Corti using non-decalcified frozen sections of the guinea pig's cochlea. The distribution of SDH activity was found to increase from the apex to the basal turn. At each turn, SDH activity of the inner hair cells, the inner supporting cells and the nerve endings surrounding the supporting cell and on the hair cells presented a greater activity than that found in the outer hair cells, adjacent Deiter's cells and associated nerve endings. It was further observed that GM had a greater effect on SDH activity in the basal turn than the other turns. At each turn, a more sensitive area of response to GM was found on the nerve endings one each hair cell, especially on the outer hair cells of the basal turn. PMID- 1859652 TI - Immune response after collagen injection for laryngeal rehabilitation: development of an enzyme-linked immunosorbent assay. AB - The appearance of circulating antibodies directed against bovine collagen has been observed in dermatology after collagen injections with or without clinical reactions. Knowing the serologically positive patients among the clinically negatives ones is important if a second collagen injection should be planned. In these cases, skin and blood tests have to be carefully checked to confirm reactivity. In connection with this, we have developed an enzyme-linked immunosorbent assay (ELISA) for determining the response to GAX collagen injections. Such injections induce a very low rate of anti-collagen antibodies. However, without having recourse to a positive control permitting statistical analysis of data, no conclusions can be made about significant positivity. In the present investigation of 12 patients following GAX collagen injections into the larynx, 1 was found to be borderline and 1 positive (17%). The positive control was made up with 20 ng/ml anti-type III collagen antibodies, which was purified and tested against type III bovine and human collagen. The present study showed that the systematic detection of antinuclear or anti-DNA antibodies after GAX collagen injection is not useful. However, the anti-collagen positivity of two control samples from 3 patients already positive for antinuclear antibodies demonstrates that bovine collagen injections are contraindicated in auto-immune disease. PMID- 1859653 TI - Blockage of longitudinal flow in endolymphatic hydrops. AB - The external shunt operation on the endolymphatic sac is based on the concept that it will drain excess endolymph and thus arrest the progression of endolymphatic hydrops. We performed histological studies on 46 temporal bones from 13 cases of bilateral and 20 cases of unilateral Meniere's disease to evaluate the status of the pathways of longitudinal flow of endolymph to the sac. The endolymphatic ducts were blocked in 8 specimens (17%), the endolymphatic sinuses in 9 (19.5%), the utricular ducts in 12 (26%), the saccular ducts in 7 (15%), and the ductus reuniens in 27 (59%). These blockages arrested longitudinal flow from both the pars superior and inferior in 21 cases (46%), the pars superior only in 3 (6.5%), and the pars inferior only in 16 (35%). In the 6 ears with all pathways open, 2 were found to have fistulae between the saccules and the perilymphatic spaces, which theoretically results in internal shunting, thus alleviating the need for the external shunt procedure. In the aggregate, therefore, 42 (91%) of 46 ears showed either areas of blockage of longitudinal flow or internal shunts that would theoretically negate the value of external endolymphatic shunt procedures. These temporal bones, however, are from an autopsy population and the severity of pathological changes is probably greater than it would have been at an earlier age when external shunt surgery might have been a therapeutic consideration. PMID- 1859654 TI - The detrimental effect of aminohydroxypropylidene bisphosphonate (APD) in otospongiosis. AB - Two middle-aged female patients with active stapedial otosclerosis and sensorineural hearing loss have been treated with aminohydroxypropylidene bisphosphonate (APD). No effect on the Schwartze sign was observed either during or following therapy. No changes were seen in the audiometric data of the patients during the 1st year. Then, within a few weeks, both patients complained of sudden deterioration of the existing hearing losses in both ears, with an alteration of tinnitus. One patient became totally, bilaterally deaf, while the other retained minimal auditory function in the low frequencies in one ear. A sudden bilateral hearing loss in cochlear otosclerosis never develops under normal circumstances and we are convinced that in the cases that we have observed it is due to the treatment with APD. PMID- 1859655 TI - Preinvasive stages of adenocarcinoma of the nose after exposure to wood dust. AB - The early stages of adenocarcinoma of the nose due to exposure to beech and oak wood dust show superficial preinvasive growth. The papillary and tubular structures of this "adenocarcinoma in situ" are identical with those of invasive adenocarcinomas. There are no indications that cuboid or squamous metaplasia precedes the development of this type of carcinoma. PMID- 1859656 TI - A comparison of hyaluronan and fibronectin in the healing of tympanic membrane perforations. AB - Fibronectin and 1% hyaluronan, two extracellular matrix components, were applied to tympanic membrane (TM) perforations, using the laboratory rat as an animal model. The perforations occupied the upper, posterior quadrant of the TM. Saline treated and untreated perforations of equal size served as controls. Fifty percent of the perforations treated daily with hyaluronan healed prior to the first closures of the other groups. The use of fibronectin did not enhance the healing rate. The hyaluronan-treated perforations were covered initially by a sheet of keratin and hyaluronan containing abundant inflammatory cells. Within this keratin-hyaluronan cover, hyperplastic stratified keratinizing epithelium advanced and bridged the gap of the perforation ahead of the approaching connective tissue. These findings indicate that exogenously applied hyaluronan could be valuable in the clinical situation and should be tried to improve the healing of TM perforations. PMID- 1859657 TI - Calcium-binding sites in the inner ear after pure-tone stimulation. AB - Five guinea pigs were exposed to an interrupted 90 dB SPL pure tone of 3.2 kHz for a total application time of 5 min. Following sound application all animals were decapitated and the cochleae were removed. After that, calcium-binding sites were located by the potassium pyroantimonate precipitation method. Another three animals served as control animals and did not receive the sound treatment. Findings confirmed previous studies showing the spatial arrangements of precipitate rich regions in the inner ear's two acellular structures (the basilar membrane and tectorial membrane) and the two cellular structures (the inner hair cells and Huschke's teeth). By using semiquantitative evaluation we found a relative diminution of precipitable calcium in inner hair cells and in Huschke's teeth of sound-exposed animals when compared to untreated animals. PMID- 1859658 TI - Clinical efficacy of budesonide in the treatment of eczematous external otitis. AB - Sixty patients with mild to moderate forms of eczematous otitis externa were treated with budesonide and placebo in a double-blind controlled study using parallel groups. Each treatment period was preceded by otomicroscopic examination and thorough cleaning of the ear canal. The symptoms and signs were assessed with a score system ranging from 0 (no symptoms/signs) to 3 (severe symptoms/signs). Budesonide treatment was associated with a reduction in severity of all symptoms recorded and a marked improvement in erythema, swelling and discharge. Mechanical cleaning of the ear canal and placebo was not a sufficient treatment for this group of patients. PMID- 1859659 TI - Inner ear fine structures of the hamster in frozen sections used for immunohistochemical assays for inner ear diseases. AB - Frozen sections of the inner ear of the hamster enable detailed investigations of the fine structures in immunofluorescence assays. At high magnification single mitochondria can be identified by their reactions with an antiserum containing antibodies against mitochondria. In the positive reaction with an antiserum against nuclei, the typical green fluorescence is restricted to the nuclei, which are mostly separated by the surrounding cytoplasm. The method of immunohistochemical assay using frozen sections from the non-decalcified inner ear is very time-consuming and cannot be recommended for the routine diagnosis of inner ear diseases, although it may be useful in research and for studying critical clinical cases. PMID- 1859660 TI - Posterior pericardial annuloplasty: a physicological correction? AB - Since the introduction of the annuloplasty ring, many attempts have been made to obtain a flexible ring that preserves the physiological motion of the mitral annulus. We experimented with a new technique using autologous pericardium to construct a more flexible ring. Twenty patients underwent mitral valve repair for degenerative disease and were treated by a posterior pericardial annuloplasty and the usual valvuloplasty procedures. A long strip of pericardium was prepared, marked with metal clips and rolled up in a tubular fashion with the serosal surface on the outside. The pericardial tube was apposed on the posterior annulus just beyond the commissures. No patient required early or late reoperation. Doppler analysis showed good valve function: 18 patients had no or mild, and 2 had moderate regurgitation. Transmitral flow indexes were nearly normal (MVA = 3.7 +/- 0.4 cm2; flow velocity peak = 1.06 +/- 0.2 m/s). Fluoroscopic examination was employed for assessing annular motion using the metal clips as radiopaque markers. Planimetry of the hemiarea showed a mild narrowing (mean 8.5% +/- 6.4%) of annular size during ventricular systole. There was a trend toward a systolic reduction of the anteroposterior diameter of the annulus. These findings demonstrate that the mitral orifice preserves its flexible properties after this type of annuloplasty. Posterior pericardial annuloplasty seems to be a physiological correction of annular dilatation in patients with degenerative disease. PMID- 1859661 TI - Coronary artery bypass surgery in patients with angina pectoris and hypothyroidism. AB - The treatment of hypothyroidism in patients undergoing coronary artery bypass surgery is a difficult clinical problem. To determine perioperative thyroid replacement therapy in patients with hypothyroidism, plasma total thyroxine (T4), total triiodothyroxine (T3), free T4, free T3 and thyroid-stimulating hormone levels were measured preoperatively and at 1, 2, 3, 7, and 14 days after operation in 9 patients with hypothyroidism and were compared with levels in 14 patients with normal thyroid function who underwent coronary bypass surgery. In the normal control group, total T4 decreased to its lowest level on the 1st postoperative day and then increased gradually to the preoperative level at 7 days. Total T4 remained within the normal range throughout the entire postoperative course. In 6 patients with hypothyroidism who were treated with thyroid hormone before surgery, total T4 decreased immediately after operation and only increased after starting thyroid replacement therapy. In 3 hypothyroid patients without prior thyroid replacement, total T4 showed a change similar to patients in the control group but remained below the normal range until starting thyroid replacement therapy. Coronary bypass surgery was performed safely in patients with hypothyroidism. Preoperative thyroid replacement with suboptimal doses was safe in patients with severe hypothyroidism. Adequate postoperative thyroid replacement was achieved in all patients without complications. PMID- 1859662 TI - Current risk of coronary bypass for unstable angina. AB - The risk associated with surgical revascularization for unstable angina is critically dependent upon the clinical presentation of the patient. For this study, between January 1982 and December 1987, clinical, angiographic, operative and hospital outcome data were collected prospectively for 6539 patients undergoing surgery for unstable angina. Urgent surgery was performed in 1523 patients (23.3%), while 5016 (76.7%) underwent semielective revascularization. The mean age was 58.9 +/- 9.2 years and 805 patients (12.3%) were aged 70 years or above. The male:female ratio was 3.6:1. Depressed left ventricular function (left ventricular ejection fraction less than 40%) was present in 27.2% of the population. Preoperative myocardial infarction (within 30 days of surgery) had occurred in 588 patients (9.0%). Operative mortality was 4.6% (301 deaths). Stepwise logistic regression analysis was performed to determine the independent predictors of operative mortality. The following variables were selected in descending order: urgent surgery (P less than 0.001), coronary reoperation (P less than 0.001), depressed left ventricular (P less than 0.001), female gender (P less than 0.001), increasing age (P less than 0.001), left main stenosis (P = 0.002), and preoperative myocardial infarction (P less than 0.001). Predicted operative mortality varied between 0.5 +/- 0.3% and 82.6 +/- 12.7%. The most important determinant for patients with a preoperative myocardial infarction was left ventricular dysfunction, whereas urgent surgery for unstable angina was the most important risk variable in those without preoperative necrosis. PMID- 1859663 TI - Comparative study between the gastroepiploic and the internal thoracic artery as a coronary bypass graft. Size, flow, patency, histology. AB - Ninety-two gastroepiploic artery (GEA) and 322 internal thoracic artery (ITA) grafts which underwent postoperative angiography (0.5-24 postoperative months, mean 2.0 months) were compared. The sites of GEA anastomosis were 5 left anterior descending, 3 diagonal, 16 circumflex and 68 right coronary arteries and for ITA grafts, 241 left anterior descending, 40 diagonal, 36 circumflex and 5 right coronary arteries. Patency rates were 96% (88/92) of GEA and 98% (314/322) of ITA, respectively. No focal stenosis in the graft trunk was found in both GEA and ITA except occasional spasm in GEA. Six (6%) GEAs were opacified via the superior mesenteric artery. Mean diameter of grafts just proximal to the anastomosis measured by angiogram was 2.3 mm in GEA and 1.9 mm in ITA (P less than 0.01). Free flow after intraluminal papaverine injection was 90.6 ml/min (50-300 ml/min) in 48 GEAs and 81.3 ml/min (50-150 ml/min) in 98 ITAs. Histology showed normal to mild intimal sclerotic changes in 58 of 63 (92%) GEAs and in 94 of 95 (99%) ITAs. From these results, we concluded that GEA is a suitable conduit and good long term patency similar to ITA grafting can be expected in coronary artery bypass grafting. PMID- 1859664 TI - Fifteen-year follow-up for double internal thoracic artery grafts. AB - The internal mammary artery (IMA) is the conduit of choice for myocardial revascularization. From 1972 to 1989, 586 patients received bilateral IMA and supplemental vein grafts. There were 506 men (86%) and 79 women (14%) with a mean age of 55.5 years (range 32-77 years). Unstable angina was present in 138 patients (24%), insulin-requiring diabetes mellitus in 83 (14%) and previous myocardial infarction (MI) in 25 (4%). Preoperative angiography demonstrated triple-vessel disease in 286 patients (49%) and double-vessel disease in the remaining 300 patients (51%). Left main coronary artery disease (stenosis greater than or equal to 50%) was present in 53 (9%). The mean left ventricular score was 7.4 with a range of 5 to 20. The mean number of grafts performed was 3.4 per patient. Hospital mortality was 3.6% (21 patients). Follow-up was done through direct patient contact, via the patient's physician or by telephone contact with the patient themselves or surviving family members. Follow-up was complete in 518 hospital survivors and ranged from 1 month to 17.5 years with a cumulative follow up of 911 patient years. At 10 and 15 years, respectively, the actuarial freedom from MI was 78% and 72% and freedom from reoperation was 93% and 86%. Actuarial survival at 10 and 15 years was 85% and 70%, respectively. This longitudinal analysis demonstrates that bilateral IMA grafting has a low operative risk. The data suggest that utilization of two IMA grafts yield excellent freedom from recurrent symptoms and provides excellent long-term survival. PMID- 1859665 TI - Lung mechanics and airway pressure transmission in infants after open heart surgery. AB - To evaluate the effects of positive airway pressure on lung mechanics and airway pressure transmission into the intrathoracic space, airway and intrathoracic pressure were recorded during stepwise lung inflation in 17 infants undergoing open heart surgery during the first year of life. Eleven of the 17 patients had cuffed tracheal tubes allowing calculation of lung and chest wall compliance. In 7 of these 11 patients, lung inflation to 2.5 ml/kg above functional residual capacity produced an improvement in initially low lung compliance. This volume increment required elevation of airway pressure by 4-11 cm H2O above ambient. Further lung inflation to 10 ml/kg did not effect an improvement in lung mechanics. In the remaining patients, initial lung compliance was high and remained unchanged throughout the range of lung inflation. Transmission of pressure into the intrathoracic space averaged 47 +/- 9% (mean +/- SD) and ranged from 33% to 61% when airway pressure was 10-15 cm H2O. The results indicate that the use of moderately elevated airway pressure is required to optimize lung distensibility in most infants immediately after open heart surgery. When evaluating circulatory effects of elevated airway pressure, assumption of a 50% pressure transmission is appropriate for clinical purposes. However, the observed wide range of pressure transmission warrants careful hemodynamic monitoring during continuous positive pressure breathing. PMID- 1859666 TI - Perioperative monitoring of total body water by bio-electrical impedance in children undergoing open heart surgery. AB - Knowledge of the changes in total body water (TBW) following cardiac surgery (OHS) in children would be of value in fluid therapy and in researching the causes and management of capillary leak. We have validated a bioelectrical impedance technique (BEI) for non-invasive estimation of TBW in children after OHS. We report the use of this method in a longitudinal study. Twenty patients (mean age 4.7 years +/- 3.5 (SD), mean weight (WT) 16.2 kg +/- 1 kg) undergoing a variety of complex OHS procedures were studied from 1 day preoperatively to 4 days postoperatively. Anaesthetic and basic bypass (CPB) techniques were uniform. Six patients underwent CPB at less than 20 degrees C, 10 at 20 degrees - 25 degrees C and 4 at 26 degrees - 33 degrees C. TBW (BEI), core (ctemp) and peripheral (ptemp) temperatures and fluid balance (TFB) were recorded at frequent intervals. TBW (by BEI) rose (P less than 0.001) following CPB in all patients from 62% +/- 9% (SD) body weight preoperatively to 73% +/- 13% in the ICU (an increase of 11% +/- 5%). TBW remained significantly elevated until the 3rd postoperative day. Multivariate analysis (MVA) confirmed that TBW was significantly related to TFB, but not to ctemp or ptemp. MVA also revealed smaller patient size (height and weight), younger age and longer CPB time as incremental risk factors for the rise in TBW. CONCLUSIONS: (1) BEI permits the non-invasive study of TBW in children after OHS, when TBW variation may be considerable. (2) The smaller the child and the longer the CPB, the greater the rise in TBW. (3) The technique should be a valuable tool in researching the major water fluxes associated with CPB in children. PMID- 1859667 TI - Immunosuppression with aerosolized cyclosporine for prevention of lung rejection in a rat model. AB - The efficacy of local delivery of aerosol cyclosporine (CsA) for prevention of lung rejection was compared with the intramuscular route (IM) in a fully allogeneic rat model (BN/LEW) of lung transplantation (LTx). Control rats (group 1, n = 6) received no CsA after LTx. Rats in group 2 (n = 10) received 4 doses of CsA in olive oil (25 mg/kg) intramuscularly starting on postoperative day (POD) 0. Group 3 (n = 9) was treated with aerosolized CsA for 3 h/day for 7 days starting on POD 0. All animals were sacrificed on POD 6. Transplanted lungs were graded histologically in a blind manner on a 0-4 scale. Control animals all showed grade 4 rejection. i.m. CsA therapy reduced lung rejection with a rejection grade of 1.8 +/- 0.35 (mean +/- SD) but was associated with a 50% incidence of pneumonia. Aerosol CsA provided better control of rejection with a rejection grade of 1.2 +/- 0.4 (group 3 vs. group 2: P less than 0.05 Wilcoxon) and none of these animals had penumonia. Trough blood levels of CsA were significantly lower in the group treated with aerosolized CsA when compared with the IM group (P less than 0.05). Therefore we conclude that: (1) aerosol CsA is effective in preventing lung allograft rejection following lung transplantation in rats, and (2) local delivery of aerosol CsA is superior to the i.m. route because better control of rejection is achieved with a lower systemic delivery of CsA. PMID- 1859669 TI - Coarctation of the aorta in complex congenital heart disease: simultaneous repair via sternotomy. PMID- 1859668 TI - Early experience with crimped bovine pericardial conduit for arterial reconstruction. AB - A bovine pericardial conduit was developed in the laboratory incorporating the principle of crimping used for synthetic vascular prostheses. The pericardium was processed in glutaraldehyde and the tube was crimped by a technique which preserves the integrity of collagen fibres. This vascular substitute presents a non-thrombogenic and non-porous inner surface which does not require preclotting and does not leak. The material is very soft, easy to handle and suture, coapts nicely to suture lines resulting in a hemostatic anastomosis. The crimping design provides longitudinal elasticity and resistance to collapsing, retains its shape with bending and avoids kinking. Crimping provides a circular tube which makes the construction of the anastomosis easier. Experimental studies in dogs demonstrated absence of thromboembolism with the conduit implanted in the abdominal aorta. Fibrin accumulation was not noted in the convexities of the crimps. This conduit was designed for aortic and pulmonary reconstruction and available in different sizes with or without a biological valve. Initial clinical experience included its use in 10 patients with aortic dissections or aortic aneurysms from August 1989 to March 1990. A reconstruction of the abdominal aorta was performed in 2 patients, the descending thoracic aorta in 2, the ascending aorta in 2 and the ascending aorta including the aortic valve and reimplantation of coronary arteries in 4. For the latter 4, composite crimped pericardial tubes containing a porcine bioprosthesis were used. An additional patient with a single ventricle underwent a Fontan type operation also employing a valved crimped pericardial conduit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1859670 TI - Current early results of pulmonary thromboendarterectomy for chronic pulmonary embolism. PMID- 1859671 TI - A tail length modifier gene discovered in the Japanese wild mice (Mus musculus molossinus). AB - The presence of the t haplotypes in strains derived from the Japanese wild mice (Mus musculus molossinus) was investigated. Crosses between the T/+ heterozygous short tailed mice and five normal tailed molossinus strains (MOL-ANJ, MOA, MOL NEM, MOM and Mns) produced no tailless mice, indicating that these strains possess no t haplotype. In contrast, tailless mice were produced by a cross between the T/+ heterozygotes and a MOL-NIS strain. Mating experiments showed that the tailless character was due to an interaction between the T gene and an autosomal recessive gene carried by the MOL-NIS strain that expresses the short tail character under the homozygous condition. We have tentatively named this gene brachyury-interacting tail length modifier (btm). It remains to be investigated whether the btm gene is located in the t complex region or in the other locus. PMID- 1859672 TI - Molecular cloning and nucleotide sequencing of the Arthrobacter dextranase gene and its expression in Escherichia coli and Streptococcus sanguis. AB - A bacterial strain, which assimilated dextran and water-insoluble glucan produced by Streptococcus mutans, was isolated from soil. The bacterium produced and secreted potent dextranase activity, which was identified as Arthrobacter sp. and named CB-8. The dextranase was purified and some enzymatic properties were characterized. The enzyme efficiently decomposed the water-insoluble glucan as well as dextran. A gene library from the bacteria was constructed with Escherichia coli, using plasmid pUC19, and clones producing dextranase activity were selected. Based on the result of nucleotide sequencing analysis, it was deduced that the dextranase was synthesized in CB-8 cells as a polypeptide precursor consisting of 640 amino acid residues, including 49 N-terminal amino acid residues which could be regarded as a signal peptide. In the E. coli transformant, the dextranase activity was detected mostly in the periplasmic space. The gene for the dextranase was introduced into Streptococcus sanguis, using an E. coli-S. sanguis shuttle vector that contained the promoter sequence of a gene for glucosyltransferase derived from a strain of S. mutans. The active dextranase was also expressed and accumulated in S. sanguis cells. PMID- 1859673 TI - [Association of aortocoronary bypass and intraoperative laser recanalization of the coronary arteries in ischemic heart disease. Initial clinical results]. AB - The work discusses the results of intraoperative laser recanalization (LR) of the coronary arteries (CA). It is shown that the method facilitates increase of the degree of myocardial revascularization after a combined operation--aortocoronary shunting and intraoperative CA LR. The intervention was carried out on 10 patients, in 9 of them retrograde CA LR was conducted for recanalization of proximal affection of the CA and one patient underwent retrograde LR of a distally occurring stenosis of the anterior interventricular artery. Among the 10 interventions 7 were successful: in 5 patients the narrowed CA lumen was completely restored without residual stenosis, in 2 patients the stenosis reduced by 50-60% with a residual stenosis of no more than 30-40%. Perforation of the CA wall occurred in 2 cases and was repaired surgically. Still in another case an attempt to perform laser recanalization of the right CA failed because of technical reasons. Reocclusion of the recanalized CA segment was encountered in the late-term period in 2 of 4 patients. The conclusion may be drawn that CA LR is an effective auxiliary method in the formation of an aortocoronary shunt. The presence of diffuse, multiple lesions of the shunted CA and occlusion of the vascular lumen, affection of the distal arterial channel of the CA are the main indications for the use of intraoperative CA LR. PMID- 1859674 TI - [Total anomalous drainage of pulmonary veins into the coronary sinus (clinical aspects, diagnosis and surgical treatment)]. AB - Total anomalous drainage of the pulmonary veins into the coronary sinus is a complicated congenital heart disease which takes a particularly severe course at early age. Its diagnosis is based on the discovery of overfilling of pulmonary circulation on radiography in a cyanotic patient, atrial septal defect and distended coronary sinus on echocardiography, and, in some cases, anomalous drainage of the pulmonary veins into the coronary sinus. The final diagnosis may be established during selective pulmonary arteriography. Operations were performed on 12 patients with this pathological condition under extracorporeal circulation and hypothermia with good results. In patients over one year of age the operation consisted in widening the atrial septal defect with resection of the part of the interatrial septum between the defect and the superior border of the coronary sinus and closure of the newly formed defect with a graft and transposition of the coronary sinus and the abnormally draining pulmonary veins into the left atrium. In patients under one year of age the interatrial septum was not resected. PMID- 1859675 TI - [Diagnosis and surgical treatment of anomalous drainage of the venae cavae]. PMID- 1859677 TI - [Surgical treatment of artificial heart valve damage developing in relation to prior surgery with extracorporeal circulation]. PMID- 1859676 TI - [Morphogenesis of apico-aortic conduit implantation (data of an experimental study]. AB - The article discusses the results of complex morphological research concerned with study of the histological structure of an extracardiac conduit in late-term periods after its implantation into the left ventricular-aortic position. The authors conducted a qualitative analysis of the morphogenesis of implantation of a conduit--an original new outlet tract from the left ventricle of the heart. The rich experimental material confirms the conclusion that the new outlet tract from the left ventricle of the heart is marked by complete functional competence adequate for conditions of systemic circulation. PMID- 1859679 TI - [Gas embolism of cerebral vessels in surgery with extracorporeal circulation (clinical and pathophysiological aspects)]. AB - Examination of 746 cardiosurgical patients revealed a statistically significant dependence between the frequency and degree of gas embolism recorded by the ultrasonic method during the operation and the probability and severity of cerebral circulatory disorders in the postoperative period. Experiments on 13 dogs showed the possibility of gas bubbles passing through the microcirculatory channel of the brain. Under satisfactory hemodynamic conditions up to 1/4 of the volume of air which has entered the cerebral arteries is "washed out" from the cerebral venous system. The revealed fact is most important in explaining the discrepancy between the frequency of gas embolism recording during the operation and the frequency of acute cerebral circulatory disorders in the postoperative period. PMID- 1859678 TI - [Experimental premises and 1st experiences in the clinical use of antibacterial vascular prostheses under circumstances of increased risk of suppuration]. AB - It was shown on the basis of laboratory and experimental data that created antibacterial vascular prostheses are marked, on the main, by local bacteriostatic and anticoagulative effect. It was found that heparin concentration of 3 to 500 U per 1 kg collagen causes a hyperadhesive effect on blood platelets and facilitates the formation of the primary thrombocytic thrombus. The free surface energy grows in this case from 34 +/- 0.8 to 66.3 +/- erg/cm2. The optimal thromboresistant effect occurs in heparin content of 1 U per 1 mg collagen. That this choice is correct is confirmed on examination of the inner surface of the prostheses with an electron microscope after being in the blood flow for 45 minutes. Bifurcation and linear antibacterial prostheses were used in 9 patients with a high risk of suppuration verified by cultures of discharge from ulcers and lymph nodes, and the presence of lymphangitis and lymphadenitis. The effect was positive in 8 patients, 2 of them had superficial suppuration of the operative wounds. PMID- 1859680 TI - [Long-term results of mitral valve prosthetics depending on the prosthesis model (ball, disk)]. AB - The authors conducted a comparative analysis of patients of 2 groups--with a MK4 model ball prosthesis and an folding disc prosthesis. It was found that the number of late-term (repeated) thromboembolic complications was significantly less in patients with a disc prosthesis (3.95 cases per 100 patient-years) and 4.28 cases among patients with a ball prostheses. No fatal outcomes associated with thromboembolism occurred among patients with a disc prosthesis, the lethality among those with a ball prosthesis was 27.5%. The advantages of a disc prosthesis in indices of physical activity and increased survival were also established. PMID- 1859681 TI - [Prospective modeling of coronary bypass surgery]. AB - Operation for mammary-coronary shunting was reproduced on experimental dogs. Myocardial perfusion during shunting was accomplished through a shunt, passing in the mammary artery and introduced into the distal part of the coronary artery through an incision. This allowed the use of extracorporeal circulation and the development of myocardial ischemia to be avoided. The method makes it possible to create stenoses in any part of the vascular block. The authors analysed the dependence between the coronary blood flow and the pressure in the left ventricle and aorta by means of a mathematical model, which made it possible to separate the effect produced on the coronary blood flow by such parameters as the resistance and capacity of the large vessels, resistance of small vessels, pressure of arrest of the blood flow, and extravascular compression. PMID- 1859682 TI - [Surgical treatment of "minor" forms of bronchiectasis]. AB - A total of 835 operations were conducted for bronchiectasis on 734 patients (75.9% were children and adolescents). The late-term results of operations for "minor" forms of the disease in 118 patients are discussed. The increase of the proportion of "minor" forms in the structure of bronchiectasis calls for changes of the tactics with prevalence of segmental and polysegmental lung resections. The relative number of the last named has been constantly growing in the recent 2 decades. The methods for determining the volume of the operation in bronchiectasis must be improved. All patients who underwent operation for "minor" forms of bronchiectasis must be kept under dynamic observation and more than half of them must be given regular anti-recurrence treatment for some years. PMID- 1859683 TI - [Results of the surgical treatment of pleural empyema after lung resection and pneumonectomy]. AB - Pneumothorax was treated by operation in 189 patients, after pneumonectomy in 111 of them and after various types of lung resection in 78. The treatment was complex in character but surgery was the principal method. The choice of the operation was guided by various factors, but the determinants were the phase of the empyema, the presence of a bronchial fistula, and the volume of the first lung resection. Postoperative complications occurred in 32.8% of cases, lethality was 11.5%. Complications developed most frequently after extensive and traumatic operations for removal of remaining parts of the lung after the type of pleuropneumonectomy. On the whole, operative methods allowed recovery or improvement to be achieved in 76.2% of patients in whom nonoperative methods failed to cure of produce a stable remission. PMID- 1859684 TI - [Use of endoscopic laser and electrosurgical interventions in thoracic surgery]. AB - A total of 320 endoscopic yttrium-aluminum-garnet laser and electrosurgical operations were carried out on 186 patients with tumors of the trachea and bronchi. Most operations were performed with the use of Friedel's respiratory bronchoscope and general anesthesia. Optimization of the methods of endoscopic laser and electrosurgical interventions made it possible to achieve a positive clinical result in the form of recanalization of the stenosis and arrest of bleeding in 143 (75.3%) patients. Laser and electrosurgical endothoracic operations performed through a thoracoscope in 81 patients with traumatic and spontaneous pneumothorax removed the cause of the pneumothorax in most of them and allowed endoscopic hemostasis to be conducted and thoracotomy to be avoided in some of them. PMID- 1859685 TI - [Causes, surgical treatment and prevention of chondritis and osteomyelitis of the ribs and sternum]. AB - The causes of chondritis and osteomyelitis of the ribs and sternum in 33 patients were analysed. It was found that in 70% of them purulent inflammation developed in the first 2-12 weeks after injury to and operations on the thoracic and abdominal organs. The average duration of the disease prior to hospitalization was about 16 months. Pathogenic microflora was isolated from the secretions of the affected tissues in 70.96% of patients. Different forms of the clinical course of the disease were distinguished according to the manifestation of the principal symptom: infiltrative-inflammatory, algesic, fistulous, empyema-like, mediastinitis-like, and a form poor in symptoms. The results of nonoperative treatment were studied. The use of X-ray therapy in a complex with nonoperative measures in 9 (25.71%) patients proved to be ineffective. Surgery was the main method for the management of chondritis and osteomyelitis of the ribs and sternum. It led to recovery of 31 (89.57%) patients without a second surgical intervention. PMID- 1859686 TI - [Experience in the diagnosis and treatment of malignant and benign tumors of the chest]. AB - The article analyses the follow-up of 155 patients among whom 63 had malignant tumors, 65 had benign tumors, while in 27 patients the tumor-like lesions were recognized as posttraumatic and post-inflammatory processes. Among 61 patients with sarcomatous lesions of the thoracic wall 21 had a resectable tumor. Operation was undertaken as a component of combined treatment in 21 patients. In a group of 19 patients 10 (16.4% of those admitted for treatment) have a survival period of 6 months to 18 years without signs of tumor growth. The other patients died in periods of 3 to 18 months. In a group of 65 patients with benign tumors 51 were treated by operation. Complications were not encountered. Among 27 patients with "false" tumors 5 underwent operation. The results of the study allow combined treatment of malignant tumors of the thoracic wall to be recommended for wider application. PMID- 1859687 TI - [Syndrome of rupture of the mitral valve chordae: etiology, clinical aspects and surgical treatment]. PMID- 1859688 TI - [Experience in the use of Soviet-made disk prostheses EMIKS and LIKS]. AB - Experience in the application of and disc prostheses in 614 patients in generalized. Mitral prosthetics was conducted in 256, aortic in 229, and mitral++ aortic in 129 patients. Hospital lethality was, respectively, 3.9, 4.8, and 8.5%. In postoperative follow-up periods of up to 7 years 92.1% of patients were examined. Survival was 88.1 +/- 0.71% in the mitral, 87.0 +/- 0.62% in the aortic, and 80.2 +/- 0.84% in the mitral-aortic group. No thromboembolic complications occurred in 88.7 +/- 0.64%, 96.9 +/- 0.31%, and 88.3 +/- 0.68% of patients, respectively. In the mitral position the mid-diastolic gradient was 4.0 +/- 0.31 mm Hg on the prosthesis and 3.8 +/- 0.82 mm Hg on the prosthesis; in the aortic position the peak systolic gradient was, respectively, 23.2 +/- 0.58 and 22.4 +/- 0.7 mm Hg. At the time of examination 97% of patients belonged to I and II functional classes. PMID- 1859690 TI - [Those mysterious people came home]. PMID- 1859689 TI - [Association of myxoma of the left atrium and mitral stenosis]. PMID- 1859691 TI - [NSF's new profile (Norwegian Nurses' Association): "NSF in touch with members?"]. PMID- 1859692 TI - [Victory for neonatal nurses. How is it in other cities?]. PMID- 1859694 TI - [NSF's new profile (Norwegian Nurses' Association). More capable elected representatives--happier members]. PMID- 1859693 TI - [Child care: let parents guide children!]. PMID- 1859695 TI - [EEC directive for pregnant women: prohibition against night shift]. PMID- 1859696 TI - [We were cowards]. PMID- 1859697 TI - [AKAN (Work-Life Committee against Alcoholism and Drug Abuse)--no abstinence movement]. PMID- 1859698 TI - [Wage negotiations: spring break-up for special nurses and managers?]. PMID- 1859699 TI - ["World sensation"--old news]. PMID- 1859700 TI - [Philippines: nurses are "export commodity"]. PMID- 1859701 TI - [Nurses abroad: number of certifications halved]. PMID- 1859702 TI - [NSF's new profile (Norwegian Nurses' Association): new structure in the local plan]. PMID- 1859703 TI - [An investment in children is an investment in the future]. PMID- 1859704 TI - [NSF's new profile (Norwegian Nurses' Association)--designate free positions for professional groups]. PMID- 1859706 TI - [With the pink snowplows behind you. Interview by Marit Fonn]. PMID- 1859705 TI - [Private life is perilous. Interview by Bjorn Arild Ostby]. PMID- 1859707 TI - [From Teheran to Gjovik. Interview by Marit Fonn]. PMID- 1859708 TI - [Make quality assurance the order of the day?]. PMID- 1859709 TI - [Do nurses have something to fear?]. PMID- 1859710 TI - [Quality and accessibility]. PMID- 1859711 TI - [NSF's new profile (Norwegian Nurses' Association): paragraphs with goals remain]. PMID- 1859713 TI - [What do the architects say?]. PMID- 1859712 TI - [NSF's new profile: proposal clarified--national assembly settled]. PMID- 1859715 TI - [10 years after examination: she is manager, she works part-time. Interview by Marit Fonn]. PMID- 1859714 TI - [NSF's new profile--nurse anesthetists in or out of the NSF?]. PMID- 1859716 TI - [Take it full-time!. Interview by Marit Fonn]. PMID- 1859717 TI - [Yes, to nursing assistants]. PMID- 1859718 TI - [NSF's new profile (Norwegian Nurses' Association): lively discussion in North Trondelag]. PMID- 1859719 TI - [NSF's new profile (Norwegian Nurses' Association): districts say no]. PMID- 1859720 TI - [NSF's new profile--Oslo district: reject proposal for new structure]. PMID- 1859721 TI - [NSF's new profile--Akershus district: vague about district residents]. PMID- 1859722 TI - [NSF's new profile--Sogn and Fjordane districts: what does it mean for local apparatus?]. PMID- 1859723 TI - [NSF's new profile: reduced and more goal-oriented secretariat]. PMID- 1859724 TI - [NSF's new profile: goals will guide expenditures]. PMID- 1859726 TI - [KS (Community's Central Organization) wants an end to conflict among professions. Interview by Marit Fonn]. PMID- 1859725 TI - [NSF's new profile--what happens to my organization?]. PMID- 1859727 TI - [NSF's new profile: is there room for nurse managers in the Norwegian Nurses' Association?]. PMID- 1859728 TI - [Norwegian study support poorest in Scandinavia]. PMID- 1859729 TI - [New structure in the Norwegian Nurses' Association]. PMID- 1859730 TI - [The Norwegian Medical Society and the Norwegian Nurses' Association: agreement on management in the hospital]. PMID- 1859731 TI - [NSF's new profile: duo of leaders wants to turn the NSF toward the future. Interview by Kjell Arne Bakke and Vidar Kildahl]. PMID- 1859732 TI - [National insurance--are you depending on it? Short and sweet about national insurance]. PMID- 1859733 TI - [Home nursing: short stop in the community]. PMID- 1859734 TI - [NSF's extraordinary national assembly: important democratic principles upheld]. PMID- 1859735 TI - [NSF's changed structure: started to put into effect]. PMID- 1859736 TI - [Norwegian model should prevent the Danish from committing suicide]. PMID- 1859737 TI - [An international nursing education?]. PMID- 1859738 TI - [Sponsoring OK--but without repayment. Interview by Marit Fonn]. PMID- 1859739 TI - [Civic sector: a few central, some local]. PMID- 1859741 TI - [National insurance--are you depending on it?]. PMID- 1859740 TI - [Disbursement for special nurses]. PMID- 1859742 TI - Synergism among i.v. anaesthetics. PMID- 1859743 TI - Fibreoptic sensors in clinical measurement. PMID- 1859744 TI - Propofol sedation for outpatient upper gastrointestinal endoscopy: comparison with midazolam. AB - The objectives of this study were to assess midazolam and propofol as sedative agents for outpatient gastrointestinal endoscopy, with particular reference to recovery profile, amnesic effects, and haemodynamic state and oxygenation during the procedure. Forty consecutive patients were allocated randomly to two groups. Patients in group I (n = 19) received midazolam 81 (SEM 32) micrograms kg-1; those in group II (n = 21) received propofol 950 (400) micrograms kg-1. Both agents were administered as single injections to similar end-points of sedation. Psychomotor function was assessed using the digit symbol substitution test (DSST). Amnesia was measured with a visual memory test and subjective questionnaire. Patients in group I had a lower DSST score than those in group II (P less than 0.01), indicating a hangover effect from midazolam. Amnesia was similar in the two groups up to the time of removal of the endoscope. More patients in group II remembered removal of the endoscope (P less than 0.001). Oxygen desaturation from baseline was similar in both groups (P less than 0.01). An increase in heart rate and decrease in mean arterial pressure were noted in both groups. Propofol provided more rapid recovery compared with midazolam, but was associated with pain on injection, a short amnesia span, and reduced patient acceptance. PMID- 1859745 TI - Extradural haematoma after continuous extradural anaesthesia. AB - We report a case of extradural haematoma occurring after extradural anaesthesia in an anticoagulated patient. The diagnosis was confirmed by magnetic resonance imaging and the haematoma was evacuated surgically. A search of the literature revealed only five previous reports of extradural haematoma in association with extradural anaesthesia. PMID- 1859746 TI - Non-cardiogenic pulmonary oedema after transfusion with granulocyte antibody containing blood: treatment with extracorporeal membrane oxygenation. AB - A 45-yr-old man developed severe non-cardiogenic pulmonary oedema after a blood transfusion reaction which was resistant to standard therapy. We describe its successful treatment with extracorporeal membrane oxygenation. PMID- 1859747 TI - A system for automatic feedback control of plasma potassium concentration. AB - A system is described for automatic feedback control of plasma potassium concentration in experimental animals. Plasma potassium was monitored continuously and the signal compared with the desired plasma potassium concentration. The resulting error signal controlled the infusion rates of a concentrated potassium chloride solution (50 or 200 mmol litre-1) and a solution of 50% glucose with insulin 200 u litre-1. Plasma potassium was increased or decreased to the desired concentration at various rates, dictated by the controller constants. Increases were achieved significantly faster than reductions. The system may prove useful for elucidating the fate of infused potassium and for determining the optimum rate of insulin infusion in hyperkalaemia. If adapted for clinical use, it may find applications in the management of various abnormalities of potassium homeostasis. PMID- 1859748 TI - Transfer of patients by helicopter. PMID- 1859749 TI - Deep venous thrombosis and anaesthesia. PMID- 1859750 TI - Pharmacokinetics of atracurium. PMID- 1859751 TI - Antagonism of intense atracurium-induced neuromuscular block in children. AB - Antagonism of intense neuromuscular block induced by atracurium 0.5 mg kg-1 was attempted in four groups of six children using one of two doses of neostigmine (0.05 mg kg-1 and 0.1 mg kg-1) or of edrophonium (0.5 mg kg-1 and 1.0 mg kg-1) when the first twitch of the post-tetanic count (PTC1) was 10% of control. For comparison with normal practice, a fifth group received neostigmine 0.05 mg kg-1 when the first twitch of the train-of-four was 10% of control. Total recovery time from PTC1 10% to a train-of-four ratio of 0.8 was not reduced by early administration of the anticholinesterases, compared with conventional administration of neostigmine at T1 10%. However, recovery from intense block was faster after neostigmine than edrophonium (P less than 0.01). Doubling the doses of the anticholinesterases did not reduce the recovery time and had the effect of increasing variability. We conclude that there is no clinical advantage in attempting to antagonize intense neuromuscular block in children using normal or increased doses of neostigmine or edrophonium. PMID- 1859752 TI - Headache after continuous spinal anaesthesia. PMID- 1859753 TI - Midazolam and erythromycin. PMID- 1859754 TI - Haemodynamic effects and outcome analysis of hypotensive extradural anaesthesia in controlled hypertensive patients undergoing total hip arthroplasty. AB - We have examined the safety of induced hypotension produced by extradural anaesthesia in patients with medically controlled hypertension. The haemodynamic response to induced hypotension was assessed in 38 non-hypertensive and 31 controlled hypertensive patients. All received extradural anaesthesia to T4 or above which decreased mean arterial pressure to 52 mm Hg and 55 mm Hg in normotensive and hypertensive patients, respectively. Cardiac output (thermodilution) was maintained by low dose i.v. infusions of adrenaline (1-5 micrograms min-1). No differences in the haemodynamic response to induced hypotension were observed in hypertensive patients. Data were collected also from 987 consecutive patients (353 hypertensive and 634 non-hypertensive) undergoing total hip replacement. Patients with hypertension were significantly older (68 vs 60 yr; P less than 0.001) and had greater ASA ratings (P less than 0.001). The smallest recorded systolic pressures were reduced more in patients with hypertension (57% vs 52%, respectively; P less than 0.001). The mean duration of maintained intraoperative hypotension (100 and 98 min) and estimated intraoperative blood loss (278 vs 281 ml) were similar in each group. After operation, two patients developed myocardial infarctions. None developed acute renal failure or stroke. There were three deaths; one of a patient who had hypertension. This suggests that induced hypotension with extradural anaesthesia is a safe technique for patients with medically controlled hypertension undergoing total hip arthroplasty. PMID- 1859755 TI - Comparison of invasive and non-invasive measurements of continuous arterial pressure using the Finapres. AB - A comparison was made of arterial pressures measured invasively from a radial arterial cannula and non-invasively from the middle finger using the 2300 Finapres (Ohmeda) during induction and maintenance of anaesthesia. Digital outputs of both pressures were captured directly onto computer hard disk; data recorded during flushing of the arterial line were excluded from analysis. We studied 53 patients undergoing cardiac, major vascular and neurosurgical procedures; 17705 comparisons of systolic, diastolic and mean pressure were analysed. Overall correlations between Finapres and invasive pressures were poor (r = 0.82, 0.68 and 0.78 for systolic, diastolic and mean pressures, respectively). The Finapres exhibited a high level of accuracy and precision in some recordings. However, patient data sets showed marked variability in average pressure differences (invasive minus Finapres) when examined individually or grouped by operation type. Unexplained variations in pressure difference with time and absolute pressure were observed also. Whilst providing useful beat-to beat information on arterial pressure trends, the Finapres cannot be recommended as a universal substitute for invasive arterial pressure monitoring. PMID- 1859756 TI - Comparison of the Finapres and direct arterial pressure monitoring during profound hypotensive anaesthesia. AB - The Finapres was compared with direct intraarterial pressure monitoring in 10 patients undergoing local resection of choroidal melanoma, an operation that requires a period of profound hypotension. Good agreement was recorded for systolic arterial pressure and heart rate over a range of pressures. However, agreement of mean and diastolic pressures was poor, with the Finapres tending to overestimate these values. In cases requiring profound hypotension, direct arterial pressure monitoring remains the method of choice. PMID- 1859757 TI - Thiopentone-propofol hypnotic synergism in patients. AB - The hypnotic effects of thiopentone, propofol and their combination were studied in 120 unpremedicated ASA group I patients. The end-point for induction of anaesthesia was taken as inability to open the eyes to command 60 s after the end of injection. The dose-response curves were determined by probit analysis. Isobolographic and algebraic (fractional) analyses were used to assess quantitatively the combined hypnotic effect of thiopentone and propofol and to define the type of interaction between these two drugs. The interaction between thiopentone and propofol was found to be synergistic. PMID- 1859758 TI - Pharmacokinetic model driven infusion of propofol in children. AB - A computer controlled infusion device for propofol was used to induce and maintain general anaesthesia in 20 children undergoing minor surgical procedures. The device was programmed with an adult pharmacokinetic model for propofol. During and after anaesthesia, blood samples were taken for measurement of propofol concentrations and it was found that the values obtained were systematically overpredicted by the delivery system algorithm. New pharmacokinetic microconstants were derived from our data which reflected more accurately the elimination and distribution of propofol in a prospective study involving another 10 children. PMID- 1859759 TI - Disposition of propofol at caesarean section and in the postpartum period. AB - We have compared the pharmacokinetics of a bolus dose of propofol 2 mg kg-1 in eight patients undergoing Caesarean section with those in eight postpartum patients undergoing sterilization by mini-laparotomy. The Caesarean section group had a total body clearance of (median) 31.5 (range 24.4-53.3) ml min-1 kg-1, apparent volume of distribution at steady state 5.10 (2.46-6.61) litre kg-1 and mean residence time 161 (52.3-251) min; values for the post-partum group were 33.8 (21.5-47.2) ml min-1 kg-1, 5.17 (3.47-8.09) litre kg-1 and 163 (92.3-238) min, respectively. The 95% confidence interval for the umbilical venous to maternal venous ratio of propofol at delivery was 0.62-0.86. Plasma protein binding studies showed there was less unbound propofol in maternal plasma (1.28 2.29%) compared with umbilical plasma (2.08-3.88%) (P less than 0.01). Neonatal concentrations of propofol were greater than maternal concentrations at 2 h and were in the range 0.05-0.11 micrograms ml-1 at 4 h. PMID- 1859760 TI - Gastric emptying in pregnancy. AB - The rate of gastric emptying in pregnancy was measured indirectly using the rate of paracetamol absorption in four groups of 15 patients: non-pregnant controls, first trimester patients presenting for termination of pregnancy, second trimester patients presenting for prostaglandin termination of pregnancy, and patients presenting for elective Caesarean section. All patients were fasted for 6 h and then received paracetamol tablets 1.5 g orally with water 50 ml. Blood samples were taken at 15-min intervals for 120 min and analysed for paracetamol concentration. There was no significant difference between the groups in the maximum concentration and time to maximum concentration (ANOVA). The AUC was reduced for the first trimester group at 60 and 120 min (P less than 0.05). No significant delay in gastric emptying was demonstrated in any of the three trimesters of pregnancy compared with the control group. PMID- 1859761 TI - Cardiac function in aneurysmal subarachnoid haemorrhage: a study of electrocardiographic and echocardiographic abnormalities. AB - Electrocardiographic (ECG) changes are reported frequently after subarachnoid haemorrhage (SAH). The aim of this study was to investigate the functional significance of ECG changes by echocardiographic assessment of cardiac function. Forty-five patients with intracranial aneurysms were studied. All patients had a 12-lead ECG and a two-dimensional echocardiogram. After patients with an history of chronic cardiac disease (n = 4) were excluded, only four patients were found to have wall motion abnormalities. These patients had only minor ECG abnormalities, but severe neurological dysfunction. Conversely, patients with other ECG abnormalities including the deep inverted T waves associated usually with SAH, had normal echocardiograms. We conclude that the ECG is not an accurate predictor of myocardial function after SAH and that myocardial dysfunction is related more closely to severity of neurological condition. PMID- 1859762 TI - Non-invasive measurement of cardiac output during induction of anaesthesia and tracheal intubation: thiopentone and propofol compared. AB - We have investigated the haemodynamic changes in response to induction of anaesthesia and tracheal intubation in patients who received either thiopentone 5 mg kg-1 or propofol 3 mg kg-1 followed by atracurium 0.5 mg kg-1 and fentanyl 1.5 micrograms kg-1. Anaesthesia was maintained with 0.6% enflurane and 50% nitrous oxide in oxygen with assisted ventilation. Cardiac output and heart rate (HR) were monitored continuously with a transthoracic impedence monitor. Mean HR did not change after induction in each group, but increased after tracheal intubation in both groups (P less than 0.01). Mean cardiac index (CI) decreased after induction (P less than 0.05) and decreased further after tracheal intubation in both groups (P less than 0.05). There was no difference between the two groups with respect to changes in CI and HR. Mean arterial pressure (MAP) and systemic vascular resistance (SVR) did not change significantly after induction in the thiopentone group. Both variables increased from preinduction values 1 min after tracheal intubation (P less than 0.001). In contrast, both MAP and SVR decreased after induction in the propofol group (P less than 0.001) and did not differ from preinduction values 1 min after tracheal intubation. MAP and SVR were greater in the thiopentone group compared with the propofol group after induction and tracheal intubation (P less than 0.01). PMID- 1859763 TI - Effect of thiopentone, etomidate and propofol on systemic vascular resistance during cardiopulmonary bypass. AB - We have studied the effect of thiopentone, etomidate and propofol on systemic vascular resistance (SVR) during cardiopulmonary bypass with constant pump flow in 30 patients undergoing elective coronary artery bypass surgery. SVR decreased to 78% of control values after thiopentone 4 mg kg-1, to 72% of control after etomidate 0.3 mg kg-1, and to 68% of control after propofol 2 mg kg-1; it returned to control values 10 min after administration of thiopentone and propofol and 7 min after administration of etomidate. Analysis of variance showed that there were no significant differences in the changes in SVR between the groups. PMID- 1859764 TI - Effect of P6 acupressure on postoperative vomiting in children undergoing outpatient strabismus correction. AB - A prospective, double-blind study was conducted to compare the effect of pressure at the P6 (Neikuan) point with placebo as an antiemetic in children. Sixty-six patients, ages 3-12 yr, undergoing outpatient surgery for correction of strabismus, were allocated randomly to receive either bilateral P6 acupressure or placebo during the perioperative period. The study was designed to detect a 50% difference in the incidence of postoperative vomiting between the two groups, with a 90% power of achieving a statistically significant result at the 5% level (two-tailed). The incidence of postoperative vomiting for the placebo group was 58% before discharge from hospital, 73% at home and 82% in the first 24 h after surgery. The corresponding results for the acupressure group were 58% before discharge, 71% at home and 94% in the first 24 h. These differences were not significant; P6 acupressure did not reduce the incidence of postoperative vomiting in children undergoing strabismus surgery. PMID- 1859765 TI - Preanaesthetic medication with clonidine: a dose-response study. AB - Eighty normotensive female patients were studied in a randomized, double-blind investigation, in which orally administered clonidine 0.1 mg, 0.2 mg and 0.3 mg were compared with a standard benzodiazepine premedicant. Clonidine 0.2 mg produced a significant reduction in anxiety (P less than 0.05) compared with all the other groups, and a better quality of induction of anaesthesia when compared with temazepam 20 mg and clonidine 0.1 mg. The decreases in arterial pressure and heart rate with clonidine 0.3 mg were significant compared with the other treatment groups. Hypotension persisted into the postoperative period after premedication with clonidine 0.3 mg, and this dose is not recommended as a routine premedicant. PMID- 1859766 TI - Halothane hepatitis. AB - The historical background, clinical features, morphology, epidemiology and aetiology of halothane hepatitis have been presented. Animal models of halothane hepatotoxicity have been described, although their application to humans is of doubtful significance. Two, probably distinct, forms of liver damage associated with halothane have been identified. The much more common mild form may result from reductive biotransformation of halothane, possibly influenced by genetic factors, or reduced liver oxygenation, whereas the rare fulminant form is most likely to be immune-mediated. The role of altered calcium homeostasis has not yet been established. In addition, a common mechanism for liver dysfunction associated with halogenated volatile anaesthetic agents has been proposed. The hepatotoxicity of enflurane cannot be excluded; while hepatic dysfunction after isoflurane or nitrous oxide is considered unlikely, further attention is necessary. It is too soon to comment on the hepatotoxic potential of sevoflurane or desflurane. PMID- 1859768 TI - Lung cancer staging. AB - Radiologic evaluation is an integral part of the staging of lung cancer. The potential for resection in cases of mediastinal invasion and other advanced disease places special demands on imaging techniques. The ability of CT or MR imaging to detect mediastinal invasion accurately is limited, and patients deserve the chance for cure by surgical resection in equivocal cases. Slight increments in improving accuracy in the evaluation of nodal disease has been shown by using different size criteria for different nodal stations and by evaluating nodal architecture or extracapsular spread. CT remains cost-effective in the overall evaluation of the patients, enabling the direction of invasive procedures and the elimination of unnecessary ones. In the evaluation of metastatic disease, most patients do not appear to benefit from bone scanning and, in a limited subset of patients, brain CT scanning should be performed. PMID- 1859767 TI - Detection and diagnosis of the primary tumor in lung cancer. AB - The role of radiology in the initial detection and diagnosis of primary lung cancer is well established. Recent advances in the detection of lung cancer stem from research into the visual search patterns used by a radiologist when reading a chest radiograph. Computer feedback of "visual-dwell" positions can lead to an increase in true-positive detection of lung nodules and decrease the false positive rate. Plain film radiography and CT continue as the mainstays for the characterization of lung nodules. New studies involving the use of conventional tomography to detect contrast enhancement of malignant lesions and the use of axial multiplanar reconstruction CT to demonstrate involvement of pulmonary veins by malignant lesions are detailed. Transbronchial and percutaneous transthoracic biopsy techniques are widely used to diagnose the nature of solitary pulmonary nodules. The dependent positioning of the biopsy site has been shown to decrease both the pneumothorax rate and the frequency of chest drain insertion, whereas the blood patch technique was shown not to affect the pneumothorax rate at all. PMID- 1859769 TI - The chest film in the acquired immunodeficiency syndrome. AB - This paper is a selective review of the past year's literature on the infections and neoplasms that develop in patients with the acquired immunodeficiency syndrome. In general, the recent literature supports information previously reported and includes further suggestions about the pathogenesis of findings seen on chest radiographs. PMID- 1859770 TI - Digital chest radiology. AB - With an increasing number of storage phosphor computed radiography units being installed worldwide, the evaluation of digital chest radiology is no longer being confined to experimental determinations of adequate imaging variables. There has been a substantial increase in the number of clinically based studies that have compared computed radiography with conventional film radiography. The applications of computed radiography are widening and further developments in dual-energy imaging and scanning equalization radiography have become possible through the use of phosphor storage computed radiography. Computer-assisted diagnosis applied to chest radiography may shortly be revolutionized by artificial intelligence, which is capable of assimilating both radiographic and clinical data. PMID- 1859771 TI - Computed tomographic diagnosis of diffuse lung disease. AB - Much work has been published on CT and high-resolution CT findings in diffuse lung disease. In the past year, there were a few additional reports of high resolution CT features of specific diseases. Most studies compared high resolution CT with radiographic and functional assessment of disease. Important CT and pathologic correlative studies were done and several excellent reviews of CT of diffuse lung disease were published. PMID- 1859772 TI - Imaging of pulmonary embolisms. AB - The diagnosis of pulmonary embolism remains a difficult problem. the clinical findings are insensitive and often nonspecific. The exact role of imaging, specifically ventilation-perfusion scanning, has been controversial. This year, the results of the Prospective Investigation of Pulmonary Embolism Diagnosis were published. The findings confirm that lung scintigraphy remains a key diagnostic procedure in the work-up of pulmonary embolism. "Normal" and "high"-probability scans are reliable categories and can usually be used without further investigation to make treatment decisions. "Intermediate"-and "low"-probability scans are not adequately reproducible as categories and are therefore difficult to separate. Most patients with scan results in these two categories will require further confirmatory tests. PMID- 1859773 TI - Imaging of the pleura. AB - With the use of plain radiography, CT, sonography, and more recently MR imaging, radiology has played a pivotal role in the diagnosis and treatment of patients with pleural effusions. The expanding use of CT scanning in patients with pleural disease has enhanced not only our understanding of the factors that affect the distribution of pleural fluid within the thorax, but also our understanding of pathologic and pathophysiologic changes in patients with pleural disease. This paper reviews significant recent developments in this area. PMID- 1859774 TI - Imaging of the pharynx and the esophagus. AB - In the past year there have been an unusual number of new concepts developed concerning the pharynx and the esophagus. The normal swallowing mechanism has been studied in detail using a variety of techniques that have increased our understanding of the normal and abnormal swallowing mechanism. In the esophagus, simultaneous barium swallows and esophageal manometry have created new insights into esophageal peristalsis. Based on this material, new recommendations have been developed for a standard barium swallow for the evaluation of esophageal motility. Also, findings previously considered to be abnormal, such as mild tertiary contractions, have now been demonstrated to be within normal limits. For the first time, detailed criteria for abnormal esophageal peristalsis have been described. This article reviews the literature, emphasizing those areas in which new concepts will affect the practicing radiologist. PMID- 1859775 TI - Imaging of the stomach and duodenum. AB - Twenty-two papers are reviewed; one on double contrast upper gastrointestinal tract studies and two on technical points relating to these; two on the biphasic upper gastrointestinal tract study; two on gastric cancer; and five on varied gastric topics. Six papers demonstrate continued interest in transabdominal gastroduodenal sonography. Four papers cover interventional techniques relating to the stomach, one with a novel approach to the removal of ingested metallic objects and three relating to percutaneous gastrostomy or gastroenterostomy. PMID- 1859776 TI - Imaging of the small bowel. AB - Radiologic imaging continues to play an integral role in the diagnosis and management of diseases of the small bowel. Except for the most proximal jejunal loop, which may occasionally be reached during upper gastrointestinal tract panendoscopy, and the terminal ileum, which can frequently be examined by the colonoscope, the mesenteric small intestine is the only gastrointestinal tract segment for which diagnostic study is not principally dependent upon endoscopic viewing. To the extent that radiologists assume primary responsibility in the diagnostic evaluation of the small bowel, it is essential that methods capable of accurately demonstrating small bowel morphology are appropriately applied (Maglinte et al., Radiology 1987, 163:297-305). Barium contrast studies and enteroclysis in particular remain the primary diagnostic methods in the small bowel for most clinical indications. Cross-sectional imaging modalities often provide unique diagnostic information, but their role remains either complementary to the demonstration of surface details by barium contrast studies or directed toward specific clinical circumstances that require discrete evaluation of the small-bowel wall and the adjacent tissues and organs. PMID- 1859777 TI - Imaging of the colon. AB - The highlight of articles published on radiologic examination of the colon is the increasing indication for use of the barium enema for screening for colorectal carcinoma. Radiologic screening for colorectal cancer promises to be more effective than mammograptive screening and more cost-effective than alternative means, such as colonoscopy. Important work on defocography suggests that measurements of anorectal angle and pelvic floor descent are nondiagnostic, and that rectal-wall changes are the important findings. Findings on CT scanning continue to be investigated in diseases, such as diverticulitis and tuberculosis, that affect both the colonic mucosa and pericolonic tissues. An important new trend is the use of sonography to investigate the colon for the presence of neoplasms. PMID- 1859778 TI - Imaging of the liver. AB - New developments in imaging of the liver have continued during the past year. Ultrasonography, particularly color Doppler applications, and invasive CT techniques are used with increasing frequency. New contrast agents are being tested for improved ultrasonographic detection of liver lesions, and faster imaging sequences and variations on older techniques are innovations in the field of MR imaging. Correlation studies addressed the issue of which are the best suited imaging methods for the various pathologic changes in the liver. PMID- 1859779 TI - Radiology of the pancreas. AB - This paper summarizes the major publications regarding imaging and intervention in pancreatic diseases from December 1989 through November 1990. This year, many of the most notable papers were published in the medical and surgical journals, reflecting that radiologic evaluation and intervention in patients with pancreatitis and pancreatic neoplasms are becoming standards of practice in many institutions. PMID- 1859780 TI - Diagnostic and interventional procedures for the biliary tract. AB - Various diagnostic imaging studies have been employed in the past year to evaluate the normal and abnormal biliary ductal system. Variations in the normal ductal drainage of the left lobe of the liver, in which the right lateral hepatic duct drained into the left hepatic duct, were studied because of the implications for the surgical resection of the left lobe. Choledochal cysts have been studied in adults using endoscopic retrograde cholangiopancreatography to evaluate the abnormal junction between the common bile duct and pancreatic duct and the long dilated common channel. An ultrasound study indicated that children with choledochal cysts also may have intrahepatic duct dilatation. An increased incidence of malignancy has been noted in adults with choledochal cysts, and their appearance on ultrasound, CT, and cholangiography were described. Cystic fibrosis produces abnormalities of the biliary tree, extrahepatic strictures, and more interestingly, intrahepatic ductal dilatation and abnormal contour without strictures. The usefulness of the preoperative ultrasonographic evaluation of the biliary tract in Oriental cholangiohepatitis was stressed. Bile duct abnormalities in fascioliasis were also noted on CT scans. Patterns of abnormality in the CT appearance of the thickened, contrast-enhanced, extrahepatic bile ducts were elucidated. Focal concentric, focal excentric, diffuse concentric, and diffuse excentric ducts were seen with various forms of pancreatic disease, choledocholithiasis, and various forms of cholangitis. An enhanced, thick-walled duct indicates disease, but is a nonspecific finding. Chronic cholecystitis was found to produce false-positive cholescintigram results in patients with suspected acute cholecystitis, but only in those with severe degrees of chronic cholecystitis. The results of multicenter trials using extracorporeal biliary lithotripsy in the United States have been published. They are somewhat disappointing and do not confirm the original excellent results reported in Germany for treatment of gallbladder stones. Much interest has been focused on the use of expandable metallic stents for the treatment of benign and malignant biliary obstruction. Preliminary data suggest good patency rates for benign lesions. Patency rates for malignant lesions are similar to those of previously available plastic stents. PMID- 1859781 TI - Magnetic resonance angiography in the abdomen and pelvis. AB - Magnetic resonance angiography of the abdomen, pelvis, and lower extremities is still under clinical investigation. This article represents a short review of the current literature in the subject, with emphasis on newer imaging techniques such as two-dimensional and three-dimensional gradient-echo pulse sequences, their current and future clinical applications, and their practical limitations. If the preliminary results hold up, MR angiography may become a standard tool for the evaluation of vascular disorders such as portal hypertension and renal artery stenosis, particularly in conjunction with quantitative measurements of blood flow. The published results making use of MR angiography either alone or in combination with quantitative MR flow measurements in the aorta, the portal system, and in femoral and iliac artery disease are very promising indeed. However, the studies published still comprise a very limited number of patients, and there is a paucity of well-controlled clinical studies applying standardized techniques to a large number of subjects. PMID- 1859782 TI - Imaging of the peritoneal cavity. AB - Newer techniques and applications of cross-sectional imaging of the abdomen with CT, ultrasound, and MR imaging have facilitated the diagnosis of diseases primarily involving the peritoneal cavity. CT peritoneography may aid in diagnosing complications of peritoneal dialysis, and detecting internal hernias and small peritoneal implants. Uncommon abnormalities such as sclerosing encapsulating peritonitis, cystic mesothelioma, and peritonitis from rupture of a retroperitoneal teratoma may also be diagnosed with CT or ultrasonography. PMID- 1859784 TI - Chest. PMID- 1859783 TI - Contrast material for computed tomography and magnetic resonance imaging of the gastrointestinal tract. AB - Various contrast agents are applied in both CT and MR imaging to improve the detection as well as the differentiation of focal liver lesions. In detecting hepatocellular carcinoma, the accuracy of Lipiodol-enhanced CT is comparable to that of CT during arterial portography. Tissue-specific contrast agents for the liver are superparamagnetic iron oxide particles, which are characterized by uptake in the reticuloendothelial system, and the paramagnetic hepatobiliary contrast agent manganese (II)-N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5' bis(phosphate). Both substances have the potential for markedly improving the detection of malignant liver tumors. The already good differentiation of focal hepatic lesions on plain MR images can be further improved by dynamic gadolinium diethylenetriamine penta-acetic acid-enhanced MR imaging. In the diagnosis of bile duct disorders, contrast-enhanced CT continues to be the method of choice. Water applied as a gastrointestinal contrast agent improves the staging of rectal carcinoma by CT. The development of suitable orally applied gastrointestinal contrast agents has now also improved the differentiation of the intestine from other abdominal structures on MR images, and this will lead to a general improvement of abdominal MR imaging. PMID- 1859785 TI - Gastrointestinal tract. PMID- 1859786 TI - The metabolism of lactate. AB - Lactate contents of tissues can vary during normal physiological conditions in mammals from 0.5 to over 5 mM, and higher in pathological states, suitable for measurement by NMR. Lactate itself is a dead-end metabolite, metabolized only by lactate dehydrogenase. The extent and direction of that reaction is determined by the free [NAD+]/[NADH][H+] ratio of cytoplasm with which lactate and pyruvate are in near-equilibrium. Pyruvate is a crossroads of most of the major degradative and synthetic pathways, but present in about one-tenth the amount of lactate. Information on the content of both lactate and its redox partner pyruvate is likely to provide more information on the metabolic state of tissue than are measurements of lactate alone. PMID- 1859787 TI - Multiple quantum NMR spectroscopy methods for measuring the apparent self diffusion coefficient of in vivo lactic acid. AB - Nuclear magnetic resonance spectroscopy methods are presented for measuring the apparent self-diffusion coefficient of lactic acid in vivo. These techniques incorporate diffusion-sensitive gradients into multiple quantum NMR pulse sequences that are employed for spectral editing. Both diffusion-sensitive zero quantum (ZQ) and double quantum (DQ) spectral editing techniques have been developed and the DQ method has been used to measure the apparent self-diffusion coefficient of in vivo lactic acid in H-MESO-1 human tumor xenografts subcutaneously implanted in athymic mice. PMID- 1859789 TI - Traffic accidents. Alcohol-related traffic fatalities among youth and young adults, 1982-1989. PMID- 1859790 TI - Sexually transmitted diseases. Increasing incidence of gonorrhoea and syphilis in homosexual men in Edinburgh. PMID- 1859791 TI - Acquired immunodeficiency syndrome (AIDS). AIDS-related knowledge and behaviour among teenagers, 1990. PMID- 1859788 TI - What the clinician can learn from MRS lactate measurements. AB - Lactate is of special importance in brain metabolism. In the 1980s, noninvasive methods for measurement of lactate concentration and turnover rate in living brain by 1H and 13C NMR spectroscopy were implemented in both animals and humans, opening the way to innovative examination of lactate's role in normal and deranged brain function. Early data on elevation of lactate in human visual cortex by physiologic stimulation and turnover of pathologically elevated brain lactate pools in animals and humans suggest that the new methods are likely to benefit clinical practice both directly--by providing information useful in management of individual patients--and indirectly--through improved understanding of disease processes. PMID- 1859792 TI - Syphilis. PMID- 1859793 TI - Trichinosis. Outbreak in Auvergne associated with the consumption of horseflesh. PMID- 1859794 TI - Hand ischemia. PMID- 1859795 TI - Vascular graft research: endothelial cell seeding of synthetic bypass grafts. AB - Over thirty years ago, bypass grafts first became available for human use. This technological development provided patients with improved functioning and quality of life. It is a peculiarity of nature that humans do not heal synthetic bypass grafts with an endothelial lining as other animals will. Researchers have developed the technology to take endothelial cells from a peripheral vein of a person and plant them inside a synthetic bypass graft. Now, science has progress to the point of applied research. In the application of this research to patients, knowledge will be obtained to see if seeding of grafts makes a difference. Hope is on the forefront that peripheral vascular surgery patients may be able to have synthetic grafts that are more like the vessels that they were created with and this will lead to improved functioning and quality living. PMID- 1859796 TI - Peripheral vascular trauma: case history. PMID- 1859797 TI - Management of facial arteriovenous malformations. AB - Today's management of vascular anomalies requires that the nurse be a vital element in the recovery process. Understanding the role of embolization in managing vascular lesions and keeping informed about the newest developments in this fast changing field enables the nurse to better help the patient toward a successful outcome. PMID- 1859798 TI - Chronic arterial occlusive disease of the lower extremity. PMID- 1859799 TI - Angioscopy. AB - Improved technology has made the technique of video angioscopy available. This technique, when routinely applied, can provide a wealth of important information to the vascular surgeon. The long term benefits will include improvement of surgical techniques and the potential to simplify and lower the cost of vascular surgery. The angioscope has emerged as a potentially powerful tool for today's vascular surgical team. Nurses need to be aware of this procedure so that they can provide quality care for these patients. PMID- 1859800 TI - "Adenomatous polyps of the gallbladder" adenomas of the gallbladder. AB - The finding of adenomatous polyps of the gallbladder is a rare occurrence and an unusual clinical problem. Among 2,145 patients who underwent cholecystectomy for gallbladder disease only 9 (0.4 per cent) presented with adenomatous polyps. There were 6 women and 3 men, aged 17 to 70 years. Preoperative ultrasonographic diagnosis was made in only 1 of 7 patients with gallstones, in contrast polypoid lesions within a gallbladder without stones were easily confirmed by both ultrasonography and oral cholecystography in the remaining 2 patients. All polyps were 1.0 cm or less in size and without histologic evidence of malignant change. The clinical significance of this rare condition is discussed, with particular reference to a possible role in development of gallbladder carcinoma. Surgical treatment should be advocated regardless of clinical manifestation when the polyp exceeds 1.0 cm in diameter or rapid growth of the lesion is seen on ultrasonographic follow-up examinations. PMID- 1859801 TI - Impact of the CUSA and operative ultrasound on hepatic resection. AB - New technologies have been developed for liver surgery, and, like all new technologies, they have a glamour which makes them seem desirable. There is an understanding abroad that they make liver surgery easier and open up the field to those without special training. But there is no proof that the new devices are in any way cost-effective, and certainly no proof that liver surgery has become safer since their advent. Fifty consecutive elective liver resections have been studied, almost half performed with the aid of the ultrasonic dissector and aspirator and diagnostic intraoperative ultrasound. There was no mortality in the whole group, but a 24% morbidity. Operative diagnostic ultrasound was thought to allow more precise planning of surgery. Its use was not associated with any increase in operative time, nor was there any increase in postoperative morbidity. The ultrasonic dissector and aspirator improved technique, reflected in a lower blood loss for each case, in fewer transfusions required, in a shorter postoperative hospital stay and in an ability to achieve these benefits in older patients. Neither device could be said to offer an entree to instant liver surgery. The use of the two devices apparently offered savings measured by a fall in the median postoperative hospital stay of 4.5 days, by a saving of 700 mls in median blood requirement and by a fall in transfusion rate from 64% to 9%. PMID- 1859802 TI - An unusual case of hepatic tumor. AB - A case is reported of a large hepatic tumor in a patient aged 71. Preoperative diagnostic techniques, including echography, CT and angiography, did not provide sufficient criteria for a precise diagnosis. The mass was removed with an extended right hepatectomy with no particular physiopathological consequences. Histological analysis revealed that this was a metastasis from a melonoma of the choroid, operated on 17 years previously. PMID- 1859803 TI - Construct validity of two heterosocial perception skill measures for assessing rape proclivity. AB - Rape-supportive attitudes and self-reported rape proclivity (using a measure by Malamuth, Haber, & Feshbach, 1980) were negatively correlated with decoding accuracy of women's negative cues (measured by the TRAC-D; McDonel, McFall, Schlundt, & Levenson, 1985) in an unselected sample of male college students. Better decoders of negative female cues on the TRAC-D, as well as subjects expressing fewer rape-supportive beliefs and less rape proclivity, were more conservative in their estimates of a man's justification in continuing to make sexual advances in the face of a woman's negative cues on the Heterosocial Perception Survey (HPS; McDonel, 1986). Ability to decode men's interpersonal cues was not correlated with responses on the HPS or rape attitude and proclivity measures, suggesting that specific rather than global decoding deficits were useful predictors of rape correlates. These results support the construct validity of the two social perception measures, the TRAC-D, and the HPS, as measures of rape proclivity. PMID- 1859804 TI - Self-reports of spousal violence in a Mexican-American and non-Hispanic white population. AB - As part of a survey of Los Angeles households, 1,243 Mexican Americans and 1,149 non-Hispanic whites were surveyed about their experiences of spousal violence. Questions to assess violence included both perpetration (whether they had been physically violent toward a partner) and victimization (whether they had been the victim of sexual assault by a partner). Over one-fifth (21.2%) of the respondents indicated that they had, at one or more times in their lives, hit or thrown things at their current or former spouse or partner. Spousal violence rates for Mexican Americans born in Mexico and non-Hispanic whites born in the United States were nearly equivalent (20.0% and 21.6%, respectively); rates were highest for Mexican Americans born in the United States (30.9%). While overall rates of sexual assault were lower for Mexican Americans, one-third of the most recent incidents reported by Mexico-born Mexican-American women involved the husband and approximated rape. PMID- 1859805 TI - For better or worse: attributions about drunken aggression toward male and female victims. AB - Research on attributions about drunken violence has suggested that intoxication serves to decrease responsibility attributed to aggressors while increasing responsibility attributed to victims. In this study, we used a scenario depicting a violent interaction in which intoxication of aggressor and victim and victim sex were varied. Subjects made attributions of blame, causality, responsibility, and normative judgements about aggressor and victim. In general, drunkenness made things worse for the intoxicated person in terms of observers' judgments: A drunken aggressor was blamed more than a sober aggressor, an intoxicated victim- whether male or female--was blamed more than a sober victim, and aggression toward a drunken victim was rated as more acceptable than aggression toward a sober victim. Results are discussed in terms of the use of alcohol intoxication as a gender-independent cue to blame the victim, and the increasing societal disapproval of drunkenness. PMID- 1859806 TI - Police response to wife assault in Northern Ireland. AB - To a large extent research on police response to wife assault had been dominated by the North American experience. Recent work in Britain has cast doubt on the extent to which these findings are applicable to the British context and drawn attention to the need for studies which explore the specific context in which policing occurs. It is argued that this approach has particular relevance in Northern Ireland where, in contrast to North America and Britain, the police operate in a context of political violence. Using data obtained from a series of semi-structured interviews with 67 women who defined themselves as victims of wife assault, the study examines police response in Northern Ireland. While the results indicate similar patterns of police response in Northern Ireland as those found elsewhere, the results also suggest that factors specific to the Northern Ireland context may influence women's use of the police, police procedures and police attitudes, and women's experience as victims. PMID- 1859807 TI - A multimethod approach to the assessment of physical abuse. AB - Numerous and heterogeneous symptoms of maladjustment have been documented among victims of physical abuse. Much of the well-controlled, theoretically guided research is rooted in methodology designed to search for group differences between abused children and a comparison group. Given the recognized methodological problems in constructing appropriate comparison groups for abused children, this study is designed to examine alternative methodological approaches. The purpose of the study is to utilize a case study to illustrate the utility of a multimethod approach to highlight intraindividual variation in the impact of abuse. This study of physically abused twin boys demonstrates that differential patterns of findings are revealed by standardized assessment in comparison to behavioral observation. The results underscore intraindividual variation in the impact of abuse. It is suggested that innate temperamental factors interact with parent-child interaction patterns to account for such intraindividual variation. PMID- 1859808 TI - History of child sexual abuse and adult sexual fantasies. AB - The study investigated the hypothesis that women with a history of childhood sexual abuse would report different sexual fantasies from women with no childhood sexual abuse. Women with a history of abuse had more force in their fantasies, had more sexually explicit fantasies, began having sexual fantasies at a younger age, and had more fantasies with the theme of being under someone's control. Women with a history of childhood physical abuse did not have a similar pattern. It was suggested that the sexual fantasies may reflect the sexualizing effect of childhood sexual experiences and that fantasies of the abusive experience may become intrusive. PMID- 1859810 TI - [Lesions of the oral mucosa. Epidemiological study of 7,297 patients]. AB - To our Knowledge, this is the first work in a number population (higher than 500 sample WHO) that is carried out in our country about lesions in the Oral Mucosa. The advantages in this Kind of studies are recognized particularly in the fields of academic, research and services. This work presents the first view of a permanent research project of Oral Mucosa Lesions at the admission clinic, School of Dentistry, Universidad del Bajio. The findings are from the evaluation of 7,297 patients, 15 years or older, that seek dental services between January 1982 and June 1989 (7.5 years). The lack of national data and the oldest population samples in other countries studies stopped wider evaluations, even though the study purpose was not affected, it was possible to offer qualitative data in the respect of prevalecence, variety and etiopathogenesis of those type of pathosis in the Oral Mucosa. The general prevalecence in the group was approximately 13%, identifying lesions more frequently in males, but higher variety in females. Report on 40 different entities, presented in general according to a descent order of prevalencece and reagrouped by sex and pathology. In half the lesions was possible to identify as the cause, acute and cronic traumatic agents; The infectious associations were also very frequent. Those last observations are of high relevance concerning the prevention of Oral Mucosa lesions. PMID- 1859809 TI - [Current status of therapy with dental implants]. AB - The objective of the present article was to review the literature concerning the use of dental implants during the last decades. It is based on the excellent paper published by Dr. Roland Meffert in the Proceedings of the World Workshop in Clinical Periodontics of 1989. The following points were analyzed: 1) The current criteria of success for dental implants. 2) The histology of the perimucosal or transgingival area surrounding the dental implants. 3) The means of retention of the different types of dental implants. 4) Four basic forms of dental implants: a) Blade-Vent implants, b) Transosteal Implants, c) Osseointegrated Implants, and d) Subperiosteal Implants. 5) The steps for the construction of an osseointegrated prosthesis. 6) The maintenance of the case. 7) Indications and contraindications of the different types of implants. 8) Conclusions. 9) Bibliography. PMID- 1859811 TI - [Observational study of craniofacial growth and development in Mexican children]. AB - The election of a investigation about craniofacial growing and development in Mexican children, was done due to a lack of national information in this rubric and as a fundamental part of the "growing and development in the scholastic" module of the Universidad Autonoma Metropolitana-Xochimilco, which work hypothesis was that "craniofacial growing and development in Mexican, 6 to 12 children in Xochimilco area are due to nutritional deficiency, second dentition eruption delay and dental maloclution "which was totality confirmed in a 100 Mexican facial characteristic children field work study, with cephalometric studies which permit to determine the craniofacial growing standard. This study was corroborated with a 40 children, 4 years later follow up. PMID- 1859812 TI - [Amelogenesis imperfecta. Description of a clinical case]. AB - A family of five was examined. Four of them presented with enamel alteration including changes in colour and loss of enamel surface. A genetic study was undertaken which revealed an autosomal dominant inheritance with complete penetration and variable expressivity. This is reflected in shape, number, extension and depth of the affected areas. Amelogenesis Imperfecta type IV was diagnosed using Shields classification. PMID- 1859813 TI - The medical care of young adults: the practice of ephebiatrics. PMID- 1859814 TI - Medical needs of performing arts students. AB - A questionnaire was administered to 71 college students enrolled in dance, drama, and musical theater programs to assess health care problems, injuries, risk taking behaviors, and sources of care. Many desired help with depression, fatigue, and chronic bone or joint pain, although 37% identified no regular physician. Thirty-nine students reported 87 injuries involving the back, foot, ankle, and knee; 12% sustained injuries at least monthly; and 72% of injuries occurred in class. The incidence of eating disorders appears to be low, as assessed by indirect measures such as body weight, oligomenorrhea, diet pill or laxative use, and scores on a body image index. The 30-day prevalence of tobacco use was 26%; marijuana, 11%; and alcohol, 71%. This survey suggests that performing arts students have important unmet health care needs. PMID- 1859815 TI - Radionuclide ventriculography in severely underweight anorexia nervosa patients before and during refeeding therapy. AB - Congestive heart failure is a well-recognized complication of refeeding therapy in underweight patients with anorexia nervosa but there are few data describing cardiac function during the critical refeeding period. This prospective study examined left ventricular function with conventional electrocardiographic-gated radionuclide ventriculography (RVG) in severely underweight anorexia nervosa patients both before and during refeeding therapy. Eight patients underwent rest and exercise RVG at admission and after regaining approximately 5% to 10% of their ideal body weight. With the admission study serving as a control, the left ventricular ejection fraction and regional wall motion analysis were analyzed before and after refeeding and weight gain. Resting left ventricular ejection fractions were not significantly different between the first and second RVGs (64 +/- 11% vs. 62 +/- 8%, respectively; P greater than .05). Likewise, the left ventricular ejection fraction with maximal exercise did not significantly differ when comparing the first or the second RVG (74 +/- 10% vs. 72 +/- 8%, P greater than .05). During the baseline RVG, the left ventricular ejection fraction increased from 64 +/- 11% (rest) to 74 +/- 10% (maximal exercise) (P less than .001). During the second RVG, the ejection fraction increased from 62 +/- 8% (rest) to 72 +/- 8% (maximal exercise) (P = .003). However, the left ventricular exercise ejection fraction in the second RVG in one patient increased only by one absolute percentage point. Four of the eight patients had regional wall motion abnormalities detected during resting and/or exercise RVG. Abnormal cardiac function occurs in asymptomatic patients with anorexia nervosa undergoing refeeding therapy. PMID- 1859816 TI - Adolescent body image during pregnancy. AB - This study compares the body perceptions of pregnant teenagers with those of their never-pregnant peers. Forty-three third-trimester pregnant girls were matched by age, race, socioeconomic status, and pubertal development to 43 never pregnant girls. Subjects were given the Tennessee Self-Concept Scale (TSCS), a self-administered questionnaire consisting of 100 self-descriptive statements which are divided into nine subscales. When compared with never-pregnant girls, the pregnant girls have a higher overall self-esteem, a more positive body image, a surer self-identity, and feel more productive as a family member, but appeared limited in their capacity for self-criticism. PMID- 1859817 TI - Depression in inner city adolescents attending an adolescent medicine clinic. AB - Interviews of 70 healthy inner city adolescents attending an adolescent medicine clinic, using the Diagnostic Interview for Children and Adolescents (DICA), revealed that 13% met criteria for current major depressive disorder. Lifetime diagnoses of major depression were found in 30% of the subjects, with many describing recurrent episodes and chronic residual symptoms. Depression in inner city adolescents represents a serious problem that may be best first detected in a medical setting. PMID- 1859818 TI - Unwanted sexual experiences among middle and high school youth. AB - Of the 1197 middle and high schoo students who participated anonymously in a health survey, 15% reported they had had a past unwanted sexual experience. Females were more likely than males and older students more likely than younger students to have had such experiences, which were categorized into six types: force/rape, child abuse, influence of drugs/alcohol, partner pressure, regret, and peer pressure. Male students tended to report peer pressure and regret more often than females, who tended to report forced situations and child abuse. The genders were similar, however, regarding partner pressure and the influence of drugs and alcohol. Students who reported having had an unwanted sexual experience were more likely to report current risk taking behaviors, school problems, and health problems that those who had not had such experiences. Students who had been physically forced were less likely to be currently sexually active and scored lower on a measure of current substance use than those who were not forced. PMID- 1859819 TI - Bibliography of recent journal articles. PMID- 1859820 TI - Folding studies of the cysteine proteinase inhibitor--human stefin A. AB - Reversible GuHCl denaturation of human stefin A (25 degrees C, pH 8) was monitored by the tyrosine fluorescence, by circular dichroism in the near UV and by circular dichroism in the far UV. In each case a midpoint of 2.8 +/- 0.1 M GuHCl was obtained, demonstrating the cooperativity of the denaturation. Kinetics of the slow folding on diluting the protein from the GuHCl denatured state, was also measured by the three spectroscopic probes (10 degrees C, pH 8). Results conform to a sequential mechanism. Denaturant concentration and temperature dependence of the slow folding were measured by fluorescence. From a linear Arrhenius plot the Ea of 100 +/- 5 kJ/mol was read. 'Double mixing' experiments revealed a slow reaction going on in the unfolded state which influenced the amplitude of the fluorescence changes. 'Double mixing' experiments performed by FPLC have shown that the folding itself, i.e., the formation of a compact state, was not dependent on the time spent under unfolding conditions. PMID- 1859821 TI - Binding sites of pyridine in cytochrome P-450cam. AB - Careful titration of oxidized cytochrome P-450cam from Pseudomonas putida with pyridine revealed deviations of the Eadie plot from linearity in the substrate bound as well as in the substrate-free protein. A binding model which assumes two binding sites for pyridine--the iron and the camphor binding site--is able to describe completely the nonlinear Eadie plot. PMID- 1859822 TI - Salt hydrates buffer water activity during chymotrypsin-catalysed peptide synthesis. AB - Chymotrypsin (EC 3.4.21.1) powder suspended in hexane in the presence of Na2CO3.10H2O is a good catalyst for peptide synthesis. The salt hydrate releases water to fix the thermodynamic water activity of the system in accord with its dissociation pressure. Salt hydrates can be useful to buffer water activity in mainly organic enzyme reaction mixtures at a value permitting activity of the catalyst while minimising hydrolytic side reactions. PMID- 1859823 TI - Characterization of a novel 14 kDa bile acid-binding protein from rat ileal cytosol. AB - A 14 kDa polypeptide in rat ileal cytosol has been identified as the major intestinal cytosolic bile acid-binding protein (I-BABP) by photoaffinity labeling with the radiolabeled 7,7-azo derivative of taurocholate (7,7-azo-TC). To further characterize I-BABP, the protein was purified by lysylglycocholate Sepharose 4B affinity and DE-52 anion-exchange chromatography. The purified I-BABP contained a single 14 kDa band on SDS-PAGE. The 14 kDa protein showed a 26-fold increase in binding affinity for [3H]7,7-azo-TC compared to cytosolic protein. Immunoblotting of protein fractions separated by affinity chromatography showed that neither liver fatty acid binding protein (L-FABP) nor intestinal fatty acid binding protein (I-FABP) bind to the affinity column and that the 14 kDa protein which bound to the column and was subsequently eluted with detergent did not cross react with anti-L-FABP or anti-I-FABP. The 14 kDa protein labeled with [3H]7,7 azo-TC was radioimmunoprecipitated from cytosol by rabbit antiserum raised against purified I-BABP. I-BABP was shown to have a blocked N-terminus; however, its mixed internal sequence generated from cyanogen bromide-cleaved protein and amino acid composition indicated that it was related to (although clearly distinct from) both I-FABP and L-FABP. These studies have isolated a 14 kDa bile acid-binding protein from rat ileal cytosol which is immunologically and biochemically distinct from I-FABP and L-FABP. PMID- 1859825 TI - Modulation of lipase hydrolysis and synthesis reactions using carbohydrates. AB - A novel method for modulation of lipase hydrolysis and synthesis lipase was investigated by using carbohydrates in the microenvironment of the Candida rugosa enzyme. The influence of the addition of different sugars to the previously dialysed enzyme was tested on the two reactions. Rates of hydrolysis were lowered by using dialysed enzyme but were increased after sugar addition, regardless of the identity of the added sugar. In contrast, synthesis reaction rates depended on the nature of the carbohydrate. Rates were increased by adding lactose, which is not a water activity depressor, but were lowered by adding fructose, glucose, sucrose or sorbitol, which are all water activity depressors. PMID- 1859824 TI - The interaction of [13C]-enriched colchicine with tubulin as determined by NMR spectroscopy. AB - [13C]Colchicine, labeled at the tropolone ring methoxy carbon, was used to study interactions with tubulin containing either Mg2+ or Mn2+ at the high affinity divalent cation binding site. Similar experiments were carried out in the presence of excess free divalent cation. The results show that: (1) when Mn2+ occupies the N-site, the 13C signal of the colchicine methoxy carbon of protein bound colchicine is not broadened, indicating that in protein-bound colchicine the tropolone methoxy group is not close to the N-site cation; (2) when excess Mn2+ is present in solution this 13C signal is severely broadened, indicating that a low affinity divalent cation site or the exchangeable site (E-site) divalent cation is situated near the colchicine binding site; and (3) in the absence of paramagnetic ions a downfield chemical shift is observed for the tropolone methoxy carbon of colchicine upon binding to tubulin, suggesting that colchicine binds near an aromatic group(s) on tubulin. PMID- 1859826 TI - Characterization of a family of high-molecular-weight plasminogen activators secreted by a lung tumor cell line. AB - In an earlier publication (Harvey, et al. (1982) J. Biol. Chem., 257, 5645-5651) the discovery of a family of unusually large molecules with plasminogen activator activity in the conditioned medium of a human lung cancer cell line was reported. These molecules are related to urokinase (uPA) by functional and immunological criteria. We have now purified two representatives of this glycoprotein family of Mr 900,000 (PA900) and Mr 660,000 (PA660). While these could be fractionated into subspecies exhibiting size and charge differences, reduction yielded in all cases two predominant chains of 70 and 40 kDa, respectively. Since the amino acid composition of the subfractions was identical, we conclude that the heterogeneity is due to demonstrated differences in glycosylation. The amino acid composition of the unreduced species and of the major reduced chains differed from that of 55 kDa uPA. These enzymes are active toward the substrate, plasminogen, as well as toward the uPA-specific synthetic substrate, Spectrozyme UK, and these activities are inhibitable by diisopropylphosphorofluoridate (DFP). Treatment of PA660 with [3H]DFP resulted in the incorporation of 1.4 mol of DFP into 1 mol of enzyme, suggesting the presence of a single active site. The label was quantitatively recovered in a 21 kDa fragment in a reduction experiment. This fragment also demonstrated immunological reactivity with antiurokinase. It is postulated that PA660 is composed of five or six pairs of the 70 and 40 kDa chains, and of a single uPA-like entity. All of these chains are linked by disfulfide bonds. Whether larger portions of uPA are also present in this molecule, is not yet clear. By electron microscopy, PA900 shows a filamentous structure, while PA660 is predominantly globular. The occurrence of large uPA-like activators in extracts of human colon carcinomas that crossreact with monospecific antibody against uPA, is discussed. PMID- 1859828 TI - The complete amino acid sequence of growth hormone of the bullfrog (Rana catesbeiana). AB - The primary structure of growth hormone (GH) isolated from the adenohypophysis of the bullfrogs (Rana catesbeiana) was determined. The hormone was reduced, carboxymethylated and subsequently cleaved with cyanogen bromide. Intact bullfrog GH was also digested with lysyl endopeptidase and trypsin. The resulting fragments were separated by reverse-phase high-performance liquid chromatography and subjected to sequence analysis using an automated gas-liquid sequencer employing the Edman method. Bullfrog GH was found to consist of 190 amino acid residues. The amino acid sequence determined is in accord with that deduced from bullfrog GH cDNA by Pan and Chang (1988) except for nine residues at positions 43 48, 73, 80 and 87. Sequence comparisons revealed that bullfrog GH is more similar to tetrapod GHs (e.g., 69% homology with sea turtle GH, 66% with chicken GH and 61% with ovine GH) than to GHs of teleosts (e.g., 35% homology with chum salmon GH and 33% with bonito GH) except for eel (52% identity). Bullfrog GH and prolactin exhibit a sequence homology of 25%. PMID- 1859827 TI - Isolation and characterization of a thermolabile beta-2 macroglycoprotein ('thermolabile substance' or 'Hakata antigen') detected by precipitating (auto) antibody in sera of patients with systemic lupus erythematosus. AB - A novel thermolabile beta-2 macroglycoprotein ('thermolabile substance' (TLS) or 'Hakata antigen' (HA], which was detected by the precipitating (auto) antibodies of patients with systemic lupus erythematosus, was isolated and characterized. The purification procedure entailed the following steps: isoelectric precipitation in the range between pH 5.2-6.1, hydroxyapatite absorption chromatography, 35% saturated ammonium sulfate precipitation, Sephadex G-200 gel filtration, Pevikon block electrophoresis, lentil lectin affinity chromatography and immobilized rabbit anti-human whole serum IgG column chromatography. Utilizing these procedures, 0.1 mg of HA was purified from 3 1 of pooled human serum. The molecular mass of HA was determined as 650 kDa by Sepharose 4B gel filtration. On SDS-PAGE analysis, HA showed a single band at 35 kDa under reduced conditions and numerous ladder bands between 35 kDa to more than 300 kDa under nonreduced conditions. On analytical ultracentrifugation, HA gave a molecular mass of 520 kDa with a single meniscus and a sedimentation constant of 12.0. The amino acid and carbohydrate analysis of reduced and S-pyridylethylated HA revealed that it contained five residues of hydroxyproline and an N-linked type sugar chain. PMID- 1859829 TI - Purification and characterization of cytochrome P-45014DM (lanosterol 14 alpha demethylase) from pig liver microsomes. AB - Cytochrome P-45014DM, which catalyzes lanosterol 14 alpha-demethylation, from pig liver microsomes was purified to a state of virtually homogeneous by gel electrophoresis. Its apparent monomeric molecular weight was estimated to be 53,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the amino terminal amino acid sequence was Gly-Leu-Leu-Thr-Gly(Leu)-Asp-Leu-Leu-Gly-Ile. When reconstituted with NADPH-cytochrome P-450-reductase, the enzyme showed a high activity for lanosterol and 24,25-dihydrolanosterol 14 alpha-demethylation. Furthermore, the oxygenated intermediates of 24,25-dihydrolanosterol 14 alpha demethylation, 32-hydroxy-24,25-dihydrolanosterol and 32-oxo-24,25 dihydrolanosterol, were converted to the 32-nor compound, 4,4-dimethylcholesta 8,14-dien-3 beta-ol, by the reconstituted enzyme system. PMID- 1859830 TI - Isolation and characterization of thermostable chitinases from Bacillus licheniformis X-7u. AB - Four kinds of thermostable chitinase were isolated from the cell-free culture broth of Bacillus licheniformis X-7u by successive column chromatographies on Butyl-Toyopearl, Q-Sepharose, and Sephacryl S-200. We named the enzymes chitinases I(89 kDa), II(76 kDa), III(66 kDa) and IV(59 kDa). Chitinases II, III and IV possessed extremely high optimum temperatures (70-80 degrees C), showing remarkable heat stability. Chitinases II, III and IV produced (GlcNAc)2 and GlcNAc from colloidal chitin and chitinase I predominantly produced (GlcNAc)2. The action pattern of chitinase I on PN-(GlcNAc)4 also showed a stronger propensity to cleave off the (GlcNAc)2 unit from the non-reducing end than the other three chitinases. Chitinases II, III and IV catalyzed a transglycosylation reaction that converted (GlcNAc)4 into (GlcNAc)6. PMID- 1859831 TI - Metabolic stereoisomeric inversion of ibuprofen in mammals. AB - Studies on the mechanism and enzymology of metabolic ibuprofen isomerization constituted the focus of this investigation. Comparative in vivo studies revealed that this biotransformation proceeded via a proton abstraction mechanism in all tested species of mammals, which is in agreement with the previous reports. Direct evidence supporting this conclusion stemmed from the in vitro epimerization of ibuprofen-CoA thioester in rat liver homogenates. Chemically synthesized (R)-ibuprofen-CoA thioester was rapidly transformed to its (S) counterpart by subcellular hepatic preparations. Examination of this epimerase activity in various rat tissue homogenates indicated that this enzyme was highly tissue specific. This biochemical reaction mainly took place in the liver and kidney, whereas low levels of enzyme activity were associated with other tissues. Nevertheless, the liver and kidney homogenates failed to invert (R)-ibuprofen directly even in the presence of all the necessary cofactors. Presumably, the failure to characterize this bioconversion was due to the lack of enzymatic acyl CoA synthesis in these homogenates. It is noteworthy that the '2-arylpropionyl CoA epimerase' catalyzed the transformation from either direction and with high turnover rates. The catalytic efficiency of (S)-ibuprofen CoA epimerization appeared to be greater than that of the (R)-counterpart. These in vitro findings suggest that the step of acyl-CoA formation assume a pivotal role in controlling the stereoselectivity and efficiency of the in vivo metabolism. As the responsible acyl-CoA synthetase(s) in different species of animals may exert the reaction with different degrees of enantiomeric preference and efficiency, the resulting stereochemical outcome and metabolic rates of this bioinversion vary accordingly. Consequently, in guinea pigs, this biotransformation proceeds in both directions with nearly equal efficiency, whereas it is virtually unidirectional and slow in humans. Currently, the purification and characterization of this novel '2-arylpropionyl-CoA epimerase' from rat livers constitute the focus of this investigation. PMID- 1859832 TI - Escherichia coli seryl-tRNA synthetase: the structure of a class 2 aminoacyl-tRNA synthetase. PMID- 1859833 TI - Anti-cruciform DNA affinity purification of active mammalian origins of replication. AB - A novel approach that employs anti-cruciform DNA monoclonal antibodies was used to isolate segments of cruciform-containing DNA from genomic DNA, in an effort to obtain fragments containing active origins of replication. High molecular weight DNA (greater than 50 kb) was extracted from log phase CV-1 cells and 6 micrograms incubated with approximately 2.5 micrograms of a monoclonal antibody, 2D3, specific for cruciform-containing DNA. The 2D3-bound DNA was digested with EcoRI and antibody-bound fragments were recovered using rabbit anti-mouse immunobeads. The beads were washed free of nonspecifically bound DNA and the 2D3-bound DNA was eluted with 2% sodium dodecyl sulphate (SDS). The yield of DNA recovered by 2D3 was 2000-fold less than the initial amount and was 17-20-fold more than that recovered nonspecifically using the control mAb, P3. The 2D3-bound DNA ranged from 0.15- greater than 23 kb with a major peak at approximately 12 kb. Specific enrichment of origin-containing DNA by 2D3 over P3 was suggested by a 10-100-fold greater recovery of a 9 kb fragment hybridizable to a low-copy monkey autonomously replicating sequence, ors 8. 20 ng of affinity-purified DNA was cloned into lambda Zap II and excised into Bluescript phagemids in vivo. Of nine randomly-selected clones between 0.15 and 3.2 kb, four were able to replicate autonomously when transfected into HeLa cells. Two of the nine clones contained sequences hybridizable to both monkey alpha-satellite and human Alu DNA, and two others to Alu alone. The present work provides further evidence for the involvement of cruciforms at active mammalian origins of DNA replication. PMID- 1859835 TI - Restructuring the translation initiation region of the human parathyroid hormone gene for improved expression in Escherichia coli. AB - Overexpression of native human parathyroid hormone in Escherichia coli was achieved by a modification of the 5' end of the genomic gene sequence, thereby adapting this part of the translation initiation region to the bacterial host. Some simple rules abstracted from optimization studies of translation initiation of a beta-interferon gene were applied. These included (a) extending complementarity of the mRNA to the anticodon loop of tRNAfMet by use of a codon with a purine nucleotide directly following the ATG, (b) avoidance of stable secondary structure in the mRNA by use of synonymous A/U-rich codons, (c) elimination of a potential second Shine-Dalgarno sequence. The appropriate silent changes led to a 20-fold increase in parathyroid hormone production resulting in 4.3% of total soluble protein. This result proves the validity of our simple approach for optimization of foreign gene expression in E. coli. PMID- 1859834 TI - Effects of protein synthesis inhibition on the transcription and transcript stability of Dictyostelium prespore genes. AB - The in vivo accumulation of several prespore transcripts of Dictyostelium discoideum has previously been shown to depend upon concomitant protein synthesis (Ratner, D.I., Pentz, W.H. and Pelletier, D.A. (1989) Biochim. Biophys. Acta 1008, 71-78). Measurements of in vivo mRNA decay and nuclear run-on transcription assays have now been used to learn whether protein synthesis is required primarily for mRNA synthesis or transcript stability. The translational inhibitors cycloheximide and pactamycin stabilized existing prespore transcripts, despite their effect upon mRNA accumulation. Transcriptional assays, performed at intervals throughout the developmental cycle, demonstrated that temporal changes in the abundance of several cell-specific transcripts correlated closely with changes in their rates of synthesis. Finally, blocking protein synthesis strongly inhibited the transcription of the prespore genes examined. These results imply that one or more developmentally regulated, labile proteins are needed for the activation of prespore gene transcription. PMID- 1859836 TI - Exonuclease III promotes in vitro binding of the replication initiator protein of plasmid pSC101 to the repeated sequences in the ori region. AB - Purified Rep protein, a replication initiator protein of plasmid pSC101, has less binding affinity for the direct repeats (DR) in the replication origin region (ori) than that for the inverted repeats (IR) in the promoter region of the structure gene of Rep (rep) (Sugiura, S. et al. (1990) J. Biochem. 107, 369-376). We found a protein factor that promotes binding of purified Rep to the DR sequence in the cell extract of Escherichia coli. In the presence of the factor, DNA fragments containing the DR sequence can form a specific DNA-protein complex by the addition of low concentrations of Rep. On the contrary, IR-containing DNA loses its binding activity for Rep by preincubation with the factor. We purified extensively the factor and identified it as exonuclease III (exo III). Enzymatic action of the factor or authentic exo III at 37 degrees C is necessary for binding of Rep to DR-DNA. This binding of Rep to duplex DNA treated with exo III is DR-sequence specific. Since Rep cannot bind to the single stranded DR sequence, the present finding suggests that partial single-stranded regions around the DR sequence are required for binding of Rep. PMID- 1859837 TI - Construction and expression of synthetic wild-type and mutant genes encoding porcine pancreatic colipase: tryptophan fluorescence studies. AB - Based on the known (95-residue) amino acid (aa) sequence of porcine pancreatic colipase (CLP), a cofactor of pancreatic lipase, a 297 bp gene was designed and assembled from eight synthetic, overlapping DNA fragments. Optimized for expression in bacteria, the CLP-encoding gene (CLP) was inserted into the lacZ gene fragment contained in the small expression vector, pUC8, and cloned in Escherichia coli JM109. Expression of this construct yielded a protein approx. 11 kDa in size, equivalent to CLP, with an Mr of 10,336, plus ten additional amino acids at the N-terminus. The recombinant CLP (reCLP) was solubilized from bacterial inclusion bodies and then purified and refolded. A mutant CLP gene, changing Tyr-55 to Trp, was then constructed by site-directed mutagenesis. Since porcine CLP contains no Trp, this strategy provided a protein with an internal fluorescent probe for biophysical studies. The presence of Trp in the mutant protein was confirmed using fluorescence spectroscopy. Both wild-type (wt) and mutant reCLP reacted on Western blots with an affinity-purified rabbit anti-CLP antibody, raised against native CLP. The Tyr-55 to Trp exchange did not affect the activity of reCLP. Fluorescence studies of the interaction between reCLP and the bile salt, taurodeoxycholate (TDOC), showed that Trp-55 in the hydrophobic binding site of mutant reCLP inserted into the interior of the bile salt micelle. PMID- 1859838 TI - The use of genetic engineering to obtain efficient production of porcine pancreatic phospholipase A2 by Saccharomyces cerevisiae. AB - We have developed an efficient production system for porcine pancreatic phospholipase A2 in Saccharomyces cerevisiae (baker's yeast). The cDNA encoding the prophospholipase A2 was expressed under the control of the galactose inducible GAL7 promotor, and secretion was directed by the secretion signals of yeast invertase. This construct yielded up to 6 mg prophospholipase A2 activity per 1 fermentation broth, secreted as a glycosylated invertase prophospholipase A2 hybrid protein. Upon genetically deleting the glycosylation site, the level of secretion decreased to 3.6 mg prophospholipase A2 per 1. Changing the invertase secretion signals for an invertase/alpha-mating factor prepro sequence-fusion increased the secretion level up to 8 mg per 1. The secreted non-glycosylated prophospholipase A2 species was correctly processed. Our results demonstrate the promises and limitations for rational design to obtain high level expression and secretion of heterologous proteins by S. cerevisiae. PMID- 1859840 TI - New elements of glucocorticoid-receptor binding sites of hormone-regulated genes. AB - The structure of the DNA regions recognized by glucocorticoid-receptor complexes (GIRC) was analyzed using frequency matrices and a modified perceptron method. Some complementary conservative elements which may modulate the efficiency of GIRC binding were found at both sides of the previously established conserved nucleotide sequence (core) (Beato, M. et al. (1987) J. Steroid Biochem. 27, 9 14). A criterion based on the concurrent use of several perceptron matrices to search for the potential GIRC binding site sequences has been worked out. By applying this criterion 73 sites were identified in 28 sequences of glucocorticoid regulated genes and 7 sites were identified in 26 sequences independent from glucocorticoid regulation. PMID- 1859839 TI - Structural characterization and tissue-specific expression of the mRNAs encoding isoenzymes from two rat mitochondrial creatine kinase genes. AB - Creatine kinase (CK; EC 2.7.3.2) isoenzymes play prominent roles in energy transduction. Mitochondrial CK (MtCK) reversibly catalyzes the transfer of high energy phosphate to creatine and exists, in the human, as two isoenzymes encoded by separate genes. We report here the cDNA sequences of the two isoenzymes of MtCK in the rat. Rat sarcomeric MtCK has 87% nucleotide identity in the 1257 bp coding region and 82% in the 154 bp 3' untranslated region as compared with human sarcomeric MtCK. Rat ubiquitous MtCK has 92% nucleotide identity over the 1254 bp coding region with human ubiquitous MtCK and 81% identity of the 148 by 3' untranslated region. Nucleotide identity between the rat sarcomeric and ubiquitous MtCK coding regions is 70%, with no conservation of their 3' untranslated regions. Thus, MtCK sequence is conserved in a tissue-specific, rather than species-specific, manner. Conservation of the 3' untranslated regions is highly unusual and suggests a regulatory function for this region. The NH2 terminal transit peptide sequences share 82% amino acid homology between rat and human sarcomeric MtCKs and 92% homology between rat and human ubiquitous MtCKs, but have only 41% homology to each other. This tissue-specific conservation of the transit peptides suggests receptor specificity in mitochondrial uptake. Rat sarcomeric MtCK mRNA is expressed only in skeletal muscle and heart, but rat ubiquitous MtCK mRNA is expressed in many tissues, with highest levels in brain, gut and kidney. Ubiquitous MtCK mRNA levels are dramatically regulated in uterus and placenta during pregnancy. Coexpression of sarcomeric and ubiquitous MtCK with their cytosolic counterparts, MCK and BCK, respectively, supports the creatine phosphate shuttle hypothesis and suggests that expression of these genes is coordinately regulated. PMID- 1859841 TI - cis-diamminedichloroplatinum (II) modified chromatin and nucleosomal core particle. AB - The influence of cis-diamminedichloroplatinum (II) (cis-DDP) binding to chromatin in chicken erythrocyte nuclei and the nucleosomal core particle is investigated. The cis-DDP modifications alter DNA-protein interactions associated with the higher order structure of chromatin to significantly inhibit the rate of micrococcal nuclease digestion and alter the digestion profile. However, cis-DDP modification of core particle has little effect on the digestion rate and the relative distribution of DNA fragments produced by microccocal nuclease digestion. Analysis of the monomer DNA fragments derived from the digestion of modified nuclei suggests that cis-DDP binding does not significantly disrupt the DNA structure within the core particle, with its major influence being on the internucleosomal DNA. Together these findings suggest that cis-DDP may preferentially bind to the internucleosomal region and/or that the formation of the intrastrand cross-link involving adjacent guanines exhibits a preference for the linker region. Sucrose gradient profiles of the modified nucleoprotein complexes further confirm that the digestion profile for micrococcal nuclease is altered by cis-DDP binding and that the greatest changes occur at the initial stages of digestion. The covalent cross-links within bulk chromatin fix a sub population of subnucleosomal and nucleosomal products, which are released only after reversal by NaCN treatment. Coupled with our previous findings, it appears that this cis-DDP mediated cross-linking network is primarily associated with protein-protein crosslinks of the low mobility group (LMG) proteins. PMID- 1859842 TI - Nucleotide sequence of a mosquito 18S ribosomal RNA gene. AB - We have sequenced an 18S ribosomal RNA gene from the mosquito, Aedes albopictus. Computer alignment of the 1950 nucleotide coding region (56% A + T) with 18S rRNA sequences from two insect and three vertebrate species revealed greater sequence divergence among the insects than among the vertebrates. Sequence alignments showed that variable region V4, which has been considered to be the most poorly conserved domain in the 18S rRNA gene, was better conserved among insects and vertebrates than was the V6 domain. PMID- 1859843 TI - cDNA cloning, sequence analysis and tissue distribution of a precursor for vasoactive intestinal contractor (VIC). AB - A full-length cDNA encoding preprovasoactive intestinal contractor (PPVIC) has been cloned. From the deduced 160 amino acid PPVIC, the mature VIC is predicted to be produced via a 37 residue intermediate, big VIC. The PPVIC also contains a VIC-like peptide of 16 amino acids structurally related to to the amino-terminal residues of VIC and flanked by pairs of dibasic amino acids, putative processing sites. RNA blot hybridization with PPVIC cDNA confirmed the PPVIC gene to be expressed in the small and large intestinal tract in a tissue specific manner. PMID- 1859844 TI - Elucidation of cDNA sequences for metallothioneins from rainbow trout, stone loach and pike liver using the polymerase chain reaction. AB - Metallothionein cDNAs were generated from the livers of three fish species and amplified by PCR. Two distinct coding sequences (A and B) were elucidated for rainbow trout metallothioneins but single isoforms were encoded by genes isolated from the stone loach and pike. Different sized transcripts were observed both with stone loach and pike but these were accounted for by altered lengths of 3' untranslated regions. PMID- 1859845 TI - Pollen specific cDNA clones from Zea mays. AB - We have cloned and sequenced four pollen-specific cDNAs. None of the clones are complete at their 5' ends. One of the clones shows significant homology to the tomato fruit-ripening polygalacturonase and to a pollen-specific polygalacturonase from Oenothera. The other three clones have no significant homologies to any reported sequence. PMID- 1859846 TI - Complete coding nucleotide sequence of cDNA for the class II RT1.B beta I chain of the Lewis rat. AB - We have established the first full length cDNA clone for the beta light chain of the MHC class II alpha, beta heterodimer (isotype RT1.B) of the rat. Clone pLR beta 118 was obtained from a self-primed lambda gt10 cDNA library of IFN-tau treated bone marrow-derived macrophages of the Lewis rat. Subcloning of pLR beta 118 into a transcription vector with subsequent in vitro transcription and translation using the reticulocyte lysate system in the presence of microsomes followed by immunoprecipitation with mAb OX6 and two-dimensional gel electrophoresis revealed the intact RT1.B beta I-chain. PMID- 1859848 TI - Liposomes for the transformation of eukaryotic cells. AB - Gene therapy of human disease is a method of treatment under active development. DNA-loaded liposomes exhibit great promise for use in this field. Liposome-based transfection vectors have many inherent advantages that will likely lead to their wide in vivo use. Vectors with low toxicity and a high degree of targetability can now be easily prepared. These vectors are also free of the length constraints governing retroviral vectors. In this review we discuss recent developments in the use of liposomes for transfection of eukaryotic cells. PMID- 1859847 TI - Cloning and characterization of the flavodoxin gene from Desulfovibrio desulfuricans. AB - The gene coding for the flavodoxin protein from Desulfovibrio desulfuricans [Essex 6] (ATCC 29577) has been cloned and sequenced. The gene was identified on Southern blots of HindIII-digested genomic DNA by hybridization to the coding region for the flavodoxin from Desulfovibrio vulgaris [Hildenborough] (Krey, G.D., Vanin, E.F. and Swenson, R.P. (1988) J. Biol. Chem. 263, 15436-15443). Ultimately, a 1.8 kb TaqI fragment was cloned which contains an open reading frame of 447 nucleotides coding for an acidic protein of 148 amino acids and calculated molecular weight of 15,726. The derived amino acid sequence of this protein is 47% identical to the flavodoxin from D. vulgaris. Regions of the polypeptide which form the flavin mononucleotide binding site are largely homologous; however, some perhaps significant differences are noted. The aromatic amino acid residues that flank the flavin isoalloxazine ring in the D. vulgaris structure, i.e., tryptophan-60 and tyrosine-98, are conserved in this flavodoxin. PMID- 1859849 TI - Glycoasparaginase in human urine. AB - Glycoasparaginase was purified 15,000-fold from human urine. The enzyme is a tetrameric protein of 86 kDa, composed of two heavy chains (25 kDa) and two light chains (18 kDa). Its structure and properties are very similar to those of human leukocyte glycoasparaginase. Glycoasparaginase activity is totally absent from urine of aspartylglycosaminuria patients. PMID- 1859851 TI - Structural characterization of a glycoprotein variant of human serum albumin: albumin Casebrook (494 Asp----Asn). AB - Albumin Casebrook is an electrophoretically slow genetic variant of human albumin with a relative molecular mass 2.5 kDa higher than normal albumin. It constitutes about 35% of total serum albumin in heterozygous carriers. The decrease in negative charge observed on incubation with sialidase suggested the presence of a carbohydrate moiety and the normalization of molecular weight following treatment with Endo-F indicated that this was an N-linked oligosaccharide. Partial acid hydrolysis and limited tryptic digestion established that the oligosaccharide was located in the C-terminal domain, between residues 367 and 585. Tryptic, chymotryptic and S. aureus V8 proteinase digestions were carried out and the resulting glycopeptides were purified on concanavalin A-Sepharose. Peptide mapping of bound and unbound fractions followed by amino acid composition and sequence analysis, established a point mutation of 494 Asp----Asn. This introduces an Asn-Glu-Thr N-linked oligosaccharide attachment sequence centered on Asn-494 and explains the increase in molecular mass. There was no apparent pathology associated with the presence of this new glycosylated albumin, which was detected in two unrelated individuals of Anglo-Saxon descent. PMID- 1859850 TI - 5-Lipoxygenase products: their biosynthesis in human gastric mucosa and possible involvement in inflammatory response and oxygen saturation index reduction in gastric ulcer patients. PMID- 1859852 TI - Plasmodium falciparum polypeptides interacting with human red cell membranes show high affinity binding to Band-3. AB - P. falciparum proteins were labelled with [35S]methionine and harvested at various asexual stages. A number of parasite proteins bound to uninfected red cell membranes (ghosts). Some of these proteins differentially partitioned when ghosts were extracted with detergent. Several of these proteins bound very strongly to immobilised whole ghost proteins or immobilised purified Band-3 in a stage-specific manner, but not to a sham-coupled matrix or to immobilised Band-3 extract from cells rendered refractory to invasion. Such specific binding of parasite proteins to immobilised Band-3 supports recent conjecture as to its role as a host receptor during parasite invasion. However, our results demonstrate the complex and multifactorial nature of the interaction between parasite and host proteins during invasion and development. PMID- 1859853 TI - The supply and distribution of dental manpower in the state of Arkansas: a report. PMID- 1859854 TI - A second messenger RNA species of transforming growth factor beta 1 in infarcted rat heart. AB - Transforming growth factor-beta 1 (TGF-beta 1) is encoded predominantly by a 2.4 kb mRNA in most tissues. However, an additional transcript of 1.9 kb can be detected in rat heart after experimental myocardial infarction caused by ligation of the left coronary artery. This transcript level is significantly higher in infarcted heart tissue than in normal heart tissue, suggesting an important role for this mRNA species in response to injury. Structural characterization of the 1.9-kb mRNA showed that it included the entire coding sequence present in the 2.4 kb TGF-beta 1 mRNA, but also contained an additional nonhomologous 3' untranslated region (UTR). The junction between the shared and unique 3' sequence in the 1.9-kb mRNA occurred only two nucleotides before the proposed polyadenylation site of the rat TGF-beta 1 2.4-kb mRNA. The unique 3'-UTR and the deduced shortened 5'-UTR in the novel 1.9-kb TGF-beta 1 mRNA suggest different transcriptional and translational regulatory mechanisms under conditions of tissue injury. PMID- 1859856 TI - [The role of separate subpopulations of bone marrow elements in regulating the proliferation processes of hemopoietic and tumor cells]. AB - The role of intercellular interactions in regulation of proliferation process in normal and tumor cells has been studied in experiments with mouse hybrids F1 (CBA X C57BL/6). The cytostatic activity to tumor cells has been shown to possess both adherent and nonadherent cells of bone marrow. The adherent cell-effectors inhibit, nonadherent ones stimulate the DNA synthesis in myelokaryocytes of normal bone marrow. During the activation of bone-marrow proliferation (under 10 hour immobilized stress) the cytostatic effect of nonadherent cells to tumor ones grows; the myelokaryocyte proliferation is stimulated on the 4th day after immobilized stress. The cytostatic activity of adherent cell-effectors remains to be low up to 7th day after immobilization. The maximum of depression in cytostatic function of the adherent elements coincides with the peak of bone marrow proliferation activity (6th day). The character of changes in cytostatic activity of adherent cells to tumor and nontumor ones is of the same type. The data obtained testify to the generality of regulation mechanisms in proliferation of tumor and normal cells. PMID- 1859857 TI - [The immunological status of Cyprinus carpio L. in experimental mycotoxicosis]. AB - Some humoral factors of nonspecific resistance have been determined in carp yearlings in 28 days after intraperitoneal administration of fungi culture filtrate (I), conidia (II), micellar extract (III) of the fungus Aspergillus fumigatus Fres., physiological solution (control). The toxicogenic and immunogenic effect of the fungus has been shown in I and II variants of the experiment respectively. The injection of fungus micella did not have any influence on the studied factors. The account of specific and quantitative composition of zooparasites in experiments and under control has been carried out; no truly differences have been revealed. PMID- 1859855 TI - Localization of the protein product of the immediate early growth response gene, Egr-1, in the kidney after ischemia and reperfusion. AB - Egr-1 is an "immediate early" gene that is induced by growth factors and agents that induce differentiation and encodes a protein with a "zinc-finger" motif. This protein is believed to be involved in transcriptional regulation. Because the fate of the kidney, and hence the organism, after an ischemic insult is dependent upon cellular repair, differentiation, and proliferation, we examined whether there was expression of the Egr-1 protein after an ischemic insult to the rat kidney. We have previously reported that Egr-1 mRNA accumulates to high levels in mouse kidneys after 30 min of ischemia and 1 h of reperfusion. In the present study, performed in rats, we show that Egr-1 mRNA transiently accumulates to very high levels after 40 min of ischemia and 1 h of reperfusion, is decreased by 3 h, and is nondetectable by 24 h of reperfusion. Reperfusion is required for Egr-1 protein accumulation to occur. The Egr-1 protein was localized by immunohistochemical techniques primarily to the nuclei of the thick ascending limbs and principal cells of the collecting ducts in the cortex and medulla. The subcellular localization was exclusively nuclear. There was some staining of the glomerular tuft and staining was particularly prominent in the parietal epithelial cells. In parallel to the accumulation of Egr-1 mRNA, the expression of the protein was transient and was no longer apparent after 5 h of reperfusion. The Egr-1 protein may play an important role in regulation of the response to ischemia of those segments of the nephron that are highly susceptible to oxygen deprivation and have a high level of intrinsic plasticity. It is possible that this protein may modulate cellular processes important for the ultimate ability of these critical nephron segments to recover from an ischemic insult. PMID- 1859858 TI - [A comparative analysis of the action of zootoxins on the isolated heart]. AB - A comparative analysis of cardiotropic activity of toxins has been studied in experiments on isolated heart of the poisonous animals from different systematic groups living on the territory of the USSR: reptiles (the venom of cobra, Vipera lebetina, Ancistrodon blomhoffi), amphibian (the venom of Bufo, Bombina, salamander), arachnids (the venom of Apis, Scolopendra, scorpion). The specific cardiotropic activity of the scorpion and Bufo venom has been discovered. The mechanisms of the cardiostimulative activity of scorpion venom have been found to be due to the activation of cellular adrenoreactive structures, and the Bufo venom to the activation of the intracellular calcium. The prospects of zootoxins using in cardiology for development of cardiotonic drugs and modelling the pathologic states in blood circulation system is substantiated. PMID- 1859859 TI - [Dot immunoenzyme analysis in biological research]. AB - The modern state, general methodologic problems and the possibilities to use in biological research the dot enzyme-linked immunosorbent assay (dot-ELISA) are analysed in the review. New types of microporous polymer membranes and equipment for the application of the solid-phase reagent and performing the assay are considered. Different variants of dot-ELISA and methods for the evaluation of results obtained in the assay as well as the ways for its optimization are discussed. PMID- 1859860 TI - [A measuring procedure for experimental determination of tensile strength of catheters and flexible probes]. AB - In order to obtain a more objective description of the properties usually subsumed under such terms as the "handling" of catheters, it is necessary to measure the significant parameter bending stiffness. A contact-free method of recording the oscillations of rod-shaped elements is presented. The stiffness EI can be calculated from the measured characteristic frequency. The logarithmic decrement can be derived from the damped natural oscillation and the damping properties of the catheter thus characterised. In addition, a consideration of imposed oscillations can be employed to calculate resonance frequency. A computer driven measuring set-up employing a CCD line camera for the non-contact recording of oscillations of rodshaped elements, together with the software required is presented. The measuring principle and possible errors are discussed and a measurement described by way of an example. PMID- 1859861 TI - [Joint prostheses components of warm-forged and surface treated Ti-6Al-7Nb alloy]. AB - In 1978 development of a TiAl alloy with the inert alloying element niobium was initiated. In 1984, the optimal composition was found to be Ti-6Al-7Nb (Protasul 100). This custom-made alloy for implants has the same alpha/beta micro-structure and equally good mechanical properties as Ti-6Al-4V. The corrosion resistance of Ti-6Al-7Nb is better than that of pure titanium and Ti-6Al-4V, due to the very dense and stable passive layer. Since 1985, highly stressed anchoring stems of various hip prosthesis designs have been manufactured from hot-forged Ti-6Al 7Nb/Protasul-100. Polished surfaces of hip, knee or wrist joints made of Ti-6Al 7Nb intended to articulate with polyethylene are surface-treated by the application of a very hard, 3-5 microns thick titanium nitride coating (Tribosul TiN), or by oxygen diffusion hardening (Tribosul-ODH) to a depth of 30 microns. PMID- 1859862 TI - [Removal of bone cement with laser]. AB - In operations requiring replacement of cemented endoprothesis, the removal of both the prosthesis and the cement is often difficult as the cement adheres strongly to the bone. Mechanical removal frequently results in fenestration or traumatisation of the bone. The aim of non-contact removal of polymethylmethacrylate (PMMA) with the laser, is to access normally inaccessible regions while inflicting a minimum amount of damage to the bone substance. The much cited cw or superpulsed CO2-laser cannot be used clinically, due to the thermal stressing of the bone. The paper shows spectra of PMMA with and without dopants, e.g. Tinuvin as UV absorber, optical staining with a high-pressure mercury lamp at lambda = 275 +/- 25 nm, lambda = 350 +/- 25 nm and various radiation times, as well as with an excimer laser lambda = 248 nm, FWHM 20 ns, and ablation measurements were made with the following lasers: excimer laser, Lambda Physics, EMG 102, FWHM 25 ns, lambda = 351 nm, excimer laser, Technolas, MAX 10, FWHM 60 ns, lambda = 308 nm, and a pulsed CO2 laser from PSI, lambda = 9.2 and 10.6 microns, FWHM 130 and 65 microseconds, pulse peak power 3.8 and 7.7 kW. The excimer laser, pulse length less than 100 ns, is unsuitable for clinical use because the required removal rate cannot be achieved either with doped PMMA or with pure PMMA. More promising results have been obtained with the pulsed (microseconds range) CO2 laser which has a removal rate of up to 30 times that of the above-mentioned excimer laser, with significantly lower thermal stressing of the bone than with the cw or super pulsed CO2 laser. PMID- 1859863 TI - Characterization of the level, target sites and inheritance of cytosine methylation in tomato nuclear DNA. AB - The tomato nuclear genome was determined to have a G + C content of 37% which is among the lowest reported for any plant species. Non-coding regions have a G + C content even lower (32% average) whereas coding regions are considerably richer in G + C (46%). 5-methyl cytosine was the only modified base detected and on average 23% of the cytosine residues are methylated. Immature tissues and protoplasts have significantly lower levels of cytosine methylation (average 20%) than mature tissues (average 25%). Mature pollen has an intermediate level of methylation (22%). Seeds gave the highest value (27%), suggesting de novo methylation after pollination and during seed development. Based on isoschizomer studies we estimate 55% of the CpG target sites (detected by Msp I/Hpa II) and 85% of the CpNpG target sites (detected by Bst NI/Eco RI) are methylated. Unmethylated target sites (both CpG and CpNpG) are not randomly distributed throughout the genome, but frequently occur in clusters. These clusters resemble CpG islands recently reported in maize and tobacco. The low G + C content and high levels of cytosine methylation in tomato may be due to previous transitions of 5mC----T. This is supported by the fact that G + C levels are lowest in non coding portions of the genome in which selection is relaxed and thus transitions are more likely to be tolerated. This hypothesis is also supported by the general deficiency of methylation target sites in the tomato genome, especially in non coding regions. Using methylation isoschizomers and RFLP analysis we have also determined that polymorphism between plants, for cytosine methylation at allelic sites, is common in tomato. Comparing DNA from two tomato species, 20% of the polymorphisms detected by Bst NI/Eco RII could be attributed to differential methylation at the CpNpG target sites. With Msp I/Hpa II, 50% of the polymorphisms were attributable to methylation (CpG and CpNpG sites). Moreover, these polymorphisms were demonstrated to be inherited in a mendelian fashion and to co-segregate with the methylation target site and thus do not represent variation for transacting factors that might be involved in methylation of DNA. The potential role of heritable methylation polymorphism in evolution of gene regulation and in RFLP studies is discussed. PMID- 1859864 TI - Accurate in vitro transcription of plant promoters with nuclear extracts prepared from cultured plant cells. AB - A simple method is presented for the preparation of nuclear extracts from suspension cultures of rice, wheat and tobacco cells. These extracts are shown to be capable of RNA Polymerase II-dependent transcription from two plant promoters in vitro; a 250 bp fragment of a wheat gliadin promoter containing sequences from -167 bp to +83 relative to the in vivo transcriptional initiation site and two fragments of the CaMV 35S promoter, containing sequences from -419 to +17, and from -90 to +17. Using the rice extract, transcription is shown to be extract dependent, DNA-dependent, alpha-amanatin-sensitive, promoter-dependent, and accurate with respect to initiation site selection on the gliadin promoter and the -90 to +17 35S promoter, but not accurate on the -419 to +17 35S promoter. PMID- 1859865 TI - Characterization of a maize cDNA that complements an enolase-deficient mutant of Escherichia coli. AB - A cDNA encoding maize enolase (2-phospho-D-glycerate hydrolase) was purified by functional genetic complementation using an enolase deficient mutant of Escherichia coli, DF261. This cDNA, pZM245, was characterized by restriction mapping and DNA sequence analysis. The cDNA contained an open reading frame encoding a protein of 446 amino acids with a high degree of similarity to enolase sequences from other organisms (72% identity to yeast enolase and 82% identity to human enolase). The pZM245 contains a correctly positioned consensus prokaryotic translation initiation sequence. The specific activity of enolase in maize increases to about twice its initial level after 48 hours of anaerobiosis. Northern-blot analysis showed a five-fold anaerobic induction in enolase mRNA, while heat shock or cold shock increased enolase mRNA levels only slightly. Southern-blot analysis of maize genomic DNA indicated that there is one copy of the pZM245 hybridizing sequence per haploid genome in maize. PMID- 1859866 TI - Differential expression of alpha-amylase genes in germinating rice and barley seeds. AB - Steady-state levels of mRNA from individual alpha-amylase genes were measured in the embryo and aleurone tissues of rice (Oryza sativa) and two varieties of barley (Hordeum vulgare L. cv. Himalaya and cv. Klages) during germination. Each member of the alpha-amylase multigene families of rice and barley was differentially expressed in each tissue. In rice, alpha-amylase genes displayed tissue-specific expression in which genes RAmy3B, RAmy3C, and RAmy3E were preferentially expressed in the aleurone layer, genes RAmy1A, RAmy1B and RAmy3D were expressed in both the embryo and aleurone, and genes RAmy3A and RAmy2A were not expressed in either tissue. Whenever two or more genes were expressed in any tissue, the rate of mRNA accumulation from each gene was unique. In contrast to rice, barley alpha-amylase gene expression was not tissue-specific. Messenger RNAs encoding low- and high-pI alpha-amylase isozymes were detectable in both the embryo and aleurone and accumulated at different rates in each tissue. In particular, peak levels of mRNA encoding high-pI alpha-amylases always preceded those encoding low-pI alpha-amylases. Two distinct differences in alpha-amylase gene expression were observed between the two barley varieties. Levels of high-pI alpha-amylase mRNA peaked two days earlier in Klages embryos than in Himalaya embryos. Throughout six days of germination, Klages produced three times as much high-pI alpha-amylase mRNA and nearly four times as much low-pI alpha-amylase mRNA than the slower-germinating Himalaya variety. PMID- 1859867 TI - Inoculation of Vicia sativa subsp. nigra roots with Rhizobium leguminosarum biovar viciae results in release of nod gene activating flavanones and chalcones. AB - Flavonoids released by roots of Vicia sativa subsp. nigra (V. sativa) activate nodulation genes of the homologous bacterium Rhizobium leguminosarum biovar viciae (R. l. viciae). Inoculation of V. sativa roots with infective R. l. viciae bacteria largely increases the nod gene-inducing ability of V. sativa root exudate (A.A.N. van Brussel et al., J Bact 172: 5394-5401). The present study showed that, in contrast to sterile roots and roots inoculated with R. l. viciae cured of its Sym plasmid, roots inoculated with R. l. viciae harboring its Sym plasmid released additional nod gene-inducing flavonoids. Using 1H-NMR, the structures of the major inducers released by inoculated roots, 6 flavanones and 2 chalcones, were elucidated. Roots extracts of (un)inoculated V. sativa contain 4 major non-inducing, most likely glycosylated, flavonoids. Therefore, the released flavonoids may either derive from the root flavonoids or inoculation with R. l. viciae activates de novo flavonoid biosynthesis. PMID- 1859868 TI - 35S-beta-glucuronidase gene blocks biological effects of cotransferred iaa genes. AB - The iaaM and iaaH genes of Agrobacterium tumefaciens and Agrobacterium rhizogenes play an important role in crown gall and hairy root disease. The iaaM gene codes for tryptophan monooxygenase which converts tryptophan into indole-3-acetamide (IAM). IAM is converted into the auxin indole-3-acetic acid (IAA) by indoleacetamide hydrolase, encoded by the iaaH gene. In functional studies on the activity of the iaa genes of the TB region of the A. tumefaciens biotype III strain Tm4, the frequently used 35S-beta-glucuronidase (35S-UidA or GUS) marker gene was found to inhibit IAA synthesis and root induction encoded by the TB iaa genes. To exert this inhibition, the 35S-UidA gene must be cotransferred with the iaaH gene. The 35S promoter alone is sufficient to cause the inhibitory effect. PMID- 1859869 TI - Expression of nuclear tRNA(Tyr) genes from Arabidopsis thaliana in HeLa cell and wheat germ extracts. AB - The transcription of thirteen Arabidopsis tRNA(Tyr) genes in a tRNA gene cluster was studied in HeLa cell nuclear extracts. All tRNA(Tyr) genes are efficiently transcribed. Initiation of transcription starts at adenosine residues at positions -5 or -6, and termination occurs at an oligo(T) stretch located 17 to 21 bp downstream of the 3' end of the structural genes depending on the gene studied. Maturation of intron-containing pre-tRNAs was compared in HeLa cell and wheat germ extracts and revealed that 5' and 3' end processing precedes splicing in both systems. Two pre-tRNAs which carry mutations in the mature domain are not processed at all in the HeLa extract, whereas one of them matures with low efficiency in the wheat germ extract. The thirteen pre-tRNAs(Tyr) possess highly conserved intron sequences of 12 nucleotides. Twelve of these introns are efficiently excised, whereas one is removed at a reduced rate, possibly due to a slightly destabilized extended anticodon stem. PMID- 1859870 TI - Stress responses in alfalfa (Medicago sativa L.). 8. Cis-elements and trans acting factors for the quantitative expression of a bean chalcone synthase gene promoter in electroporated alfalfa protoplasts. AB - A chimeric gene consisting of a bean (Phaseolus vulgaris L.) chalcone synthase (CHS) promoter fused to a bacterial chloramphenicol acetyltransferase (CAT) reporter gene was strongly expressed, and further induced by fungal elicitor, when electroporated into alfalfa (Medicago sativa L.) suspension cell protoplasts. Functional analysis of 5' deletions of the CHS promoter-CAT construct in these protoplasts indicated that the region between -326 and -130 contained both activator and silencer elements. Co-electroporation experiments confirmed that these cis-acting elements were binding sites for functionally active trans factors. In vitro DNase I footprinting revealed four potential binding sites for alfalfa suspension cell nuclear proteins between positions -326 and -130 of the CHS promoter. These sites mapped to regions shown to contain functional cis-acting elements on the basis of the deletion analysis. Three of these sites mapped to previously identified binding sites for bean nuclear proteins. Competition gel retardation analysis using oligonucleotide probes containing binding site sequences revealed sequence-specific binding of alfalfa nuclear proteins to an AT-rich element and a putative GT-1 factor consensus binding sequence. Our results define cis elements and their cognate trans factors functionally active in determining the quantitative expression of a defense response gene in a heterologous transient expression system. PMID- 1859871 TI - Nucleic acid sequence of a 21 kDa cocoa seed protein with homology to the soybean trypsin inhibitor (Kunitz) family of protease inhibitors. PMID- 1859872 TI - Electroporation of megaplasmids into Agrobacterium. PMID- 1859873 TI - Identification of the viroid-induced tomato pathogenesis-related (PR) protein P23 as the thaumatin-like tomato protein NP24 associated with osmotic stress. AB - P23, a 23 kDa pathogenesis-related (PR) protein, was purified from citrus exocortis viroid (CEVd)-infected tomato leaves. Partial amino acid sequencing of this protein including the N-terminal and nine additional tryptic fragments covering about 50% of its primary structure revealed extensive homologies to the members of the family of plant thaumatin-like proteins. Sequence alignment revealed that tomato P23 is the previously described NP24 protein found to be associated to osmotic stress in tomato. In view of this fact the possible role of pathogenesis-related P23 protein as a component of a general mechanism of response of the plant is discussed. PMID- 1859874 TI - Nucleotide sequence of 'repeat-2' of the mitochondrial DNA from the maize N cytoplasm. PMID- 1859875 TI - Dr Ham's test revisited. PMID- 1859876 TI - Autoantibody activity of immunoglobulins isolated from B-cell follicular lymphomas. AB - Previous work with monoclonal Igs (MIgs) has demonstrated that a high proportion of paraproteins bind to self-antigens such as the Fc fragment of IgG, Ii blood group antigens, cytoskeleton proteins, DNA, and myelin-associated glycoprotein (MAG). Recent work in CLL indicates that CD5+ B lymphocytes are frequently committed to production of autoantibodies. We have examined the antibody specificity of MIgs derived from the tumor cells of 31 different patients with CD5- B-cell lymphomas. Our results indicate that the tumor cells from 8 of these 31 patients (25.8%) express Igs with autoantibody activity. In two cases antibody activity was multispecific. In four cases, antibody activity was exclusively directed against the Fc fragment of IgG, whereas the two other cases bound to both Fc fragment of IgG and nuclear antigens. Most non-Hodgkin's lymphomas (NHL) are derived from CD5- B cells. These results indicate that like CLL, NHL also express Igs that frequently have autoantibody activity. PMID- 1859877 TI - Multidrug resistance (mdr1) gene expression in adult acute leukemias: correlations with treatment outcome and in vitro drug sensitivity. AB - Resistance to multiple chemotherapeutic agents has been related to the production of P-glycoprotein, a trans-membrane drug efflux pump that is encoded by the multidrug resistance (MDR) gene mdr1. To investigate whether mdr1 could be involved in clinical resistance to chemotherapy in acute leukemias, we have analyzed retrospectively the RNA from adult acute leukemia cells by slot-blot hybridization with a human mdr1 probe. Units of mdr1 expression were defined by reference to drug-sensitive human sarcoma and K562 leukemia cell lines (1 U) and the highly resistant doxorubicin selected leukemia cells K562/R7 (50 U). We studied 41 adult patients with acute leukemias: 5 acute lymphoblastic leukemias, 23 acute myeloid leukemias, and 13 secondary leukemias or blast crisis of chronic myelogenous leukemia. Expression of 10 U or more of mdr1 was found in 6 of 31 (19%) leukemias at diagnosis, versus 5 of 10 (50%) after relapse from therapy, P = .06. The complete remission rate and in vitro sensitivity to daunorubicin were both correlated with low expression (1 U, v 2 U or more) of mdr1. Among 36 evaluable attempts to induce remission, the complete remission rate was 67% (8 of 12) for patients with undetectable or minimal mdr1 expression (1 U), versus 29% (7 of 24) in patients with 2 U or more of expression, P = .03. In vitro resistance to daunorubicin or other MDR-related drugs was associated with expression of 2 U or more of mdr1 in 11 of 11 cases, while specimens that were sensitive to these agents were negative for mdr1 expression in 5 of 11 cases, P = .03. These data suggest that mdr1 expression contributes to chemoresistance in acute leukemia. Determination of mdr1 gene expression may be useful in designing therapy for patients with leukemia. PMID- 1859878 TI - Secondary erythrocytosis due to a cerebellar hemangioblastoma: demonstration of erythropoietin mRNA in the tumor. AB - Cerebellar hemangioblastoma is a rare cause of secondary erythrocytosis. Although the erythrocytosis is a result of erythropoietin (Ep) stimulation, direct evidence of Ep synthesis by the tumor has been lacking. In an erythrocytotic patient with a cerebellar hemangioblastoma we found elevated levels of Ep in the tumor cyst fluid and for the first time demonstrated Ep mRNA in the tumor by Northern blotting. This finding confirms cerebellar hemangioblastoma as a site of ectopic Ep production. PMID- 1859879 TI - Erythropoiesis in Fanconi's anemia. AB - Fanconi's anemia (FA) is an autosomal recessive condition in which greater than 90% of the homozygotes develop aplastic anemia. To determine the relation between erythroid progenitors and clinical status, blood and marrow mononuclear cells were cultured in methyl cellulose with erythropoietin, plus other hematopoietic growth factors, and growth in normal oxygen (20%) was compared with growth in low, physiologic oxygen (5%). Peripheral blood cultures were performed from 24 patients, and marrows from six. Patients were classified into six clinical groups. Group 1: Severe aplasia, transfused; one patient; no erythroid progenitors. Group 2: Severe, transfused, androgen unresponsive; one patient; no blood burst-forming units-erythroid (BFU-E). Group 3: Androgen responsive; eight patients, with decreased blood BFU-E. Group 4: Aplastic, about to start treatment; two patients; below normal numbers of colony-forming units-erythroid (CFU-E) and BFU-E. Group 5: Stable, with mild anemia, and/or thrombocytopenia, and/or macrocytosis; seven patients; with below normal numbers of blood BFU-E. Group 6: Hematologically normal; five patients; blood BFU-E low normal to normal. One marrow had normal numbers of CFU-E and BFU-E. Incubation in 5% oxygen doubled CFU-E and BFU-E only in the patients with close to normal or normal growth in 20% oxygen. Hemin and interleukin-3 increased growth slightly in those cultures where there was some growth with erythropoietin alone. Our data show that there is a correlation between current clinical status and in vitro erythropoiesis. Cultures of erythroid progenitors may also be useful predictors of hematologic prognosis in FA, although our follow-up period is too short to prove this hypothesis. PMID- 1859880 TI - Gene transfer into normal human hematopoietic cells using in vitro and in vivo assays. AB - The ability to transfer new genetic material into human hematopoietic cells provides the foundation for characterizing the organization and developmental program of human hematopoietic stem cells. It also provides a valuable model in which to test gene transfer and long-term expression in human hematopoietic cells as a prelude to human gene therapy. At the present time such studies are limited by the absence of in vivo assays for human stem cells, although recent descriptions of the engraftment of human hematopoietic cells in immune-deficient mice may provide the basis for such an assay. This study focuses on the establishment of conditions required for high efficiency retrovirus-mediated gene transfer into human hematopoietic progenitors that can be assayed in vitro in short-term colony assays and in vivo in immune-deficient mice. Here we report that a 24-hour preincubation of human bone marrow in 5637-conditioned medium, before infection, increases gene transfer efficiency into in vitro colony-forming cells by sixfold; interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) provide the same magnitude increase as 5637-conditioned medium. In contrast, incubation in recombinant growth factors IL-1, IL-3, and granulocyte-macrophage colony-stimulating factor increases gene transfer efficiency by 1.5- to 3-fold. Furthermore, preselection in high concentrations of G418 results in a population of cells significantly enriched for G418-resistant progenitors (up to 100%). These results, obtained using detailed survival curves based on colony formation in G418, have been substantiated by directly detecting the neo gene in individual colonies using the polymerase chain reaction. Using these optimized protocols, human bone marrow cells were genetically manipulated with a neo retrovirus vector and transplanted into immune-deficient bg/nu/xid mice. At 1 month and 4 months after the transplant, the hematopoietic tissues of these animals remained engrafted with genetically manipulated human cells. More importantly, G418 resistant progenitors that contained the neo gene were recovered from the bone marrow and spleen of engrafted animals after 4 months. These experiments establish the feasibility of characterizing human stem cells using the unique retrovirus integration site as a clonal marker, similar to techniques developed to elucidate the murine stem cell hierarchy. PMID- 1859881 TI - Inhibition of hematopoiesis in normal human long-term marrow cultures treated with recombinant human macrophage colony-stimulating factor. AB - The effects of recombinant human macrophage colony-stimulating factor (rhCSF-1) in long-term marrow cultures (LTMC) established from normal bone marrow cells were examined. When added during the first 3 weeks of culture (every second day, at 15 ng/mL), rhCSF-1 strongly inhibited the growth of all hematopoietic progenitors analyzed (colony-forming unit-MIX [CFU-MIX], CFU-granulocyte macrophage [CFU-GM], CFU-M, CFU-G, burst-forming unit-erythroid). Paralleling the inhibition of progenitors was the complete loss of adipocytes from the stromal layer of rhCSF-1-treated cultures. The inhibitory effect of rhCSF-1 correlated in all instances with the accumulation in the supernatants of these cultures of an activity (different from CSF-1) that inhibited colony formation in semisolid cultures. When addition of rhCSF-1 was delayed 3 weeks, its inhibitory effects were significantly reduced, which correlated with reduced inhibitory activity detected in the supernatants. Analysis of CSF-1 concentration by radioreceptor assay confirmed that added rhCSF-1 increased culture CSF-1 levels and showed that the decreased inhibition observed when rhCSF-1 is added later in culture was not due to decreased CSF-1 levels at that point. In contrast, the ability of rhCSF-1 to inhibit hematopoiesis and accumulate inhibitory activity in LTMC correlated with its rate of utilization, much higher in the first 2 weeks of culture, when the stromal layer was being established, than later. These observations document the inhibitory effect of rhCSF-1 on all aspects of hematopoiesis conducted in cultures that simulate the hematopoietic microenvironment, demonstrate the importance of accessory/stromal cells in mediating the effects of rhCSF-1 in LTMC, and point to an inhibitory activity as the mediating agent. PMID- 1859882 TI - Examination of the roles of glycoprotein Ib and glycoprotein IIb/IIIa in platelet deposition on an artificial surface using clinical antiplatelet agents and monoclonal antibody blockade. AB - The mechanism of platelet thrombus growth on an artificial surface is incompletely understood. While glycoprotein (GP)Ib and GPIIb/IIIa are required for normal attachment and thrombus formation on subendothelium, their roles in platelet deposition to artificial surfaces remain unclear. Using selected platelet inhibitors (aspirin [ASA], low molecular weight dextran, monoclonal antibodies 10E5 [v GPIIb/IIIa], and 6D1 [GPIb]) we examined the mechanism of platelet deposition to polyethylene (PE) surfaces under steady laminar and oscillatory flow conditions. Polyethylene-100 (PE-100) tubes (0.86 mm internal diameter) were perfused under steady laminar flow with citrated human whole blood reconstituted with 111indium-labeled platelets at 312 seconds-1 shear rate in the presence and absence of platelet inhibitors. The effect of oscillatory flow on platelet deposition was examined in a microwell system using 3/16-inch diameter discs of National Heart, Lung, and Blood Institute primary reference PE as the test surface. ASA and dextran did not significantly (P greater than .05) inhibit platelet deposition in laminar flow (not tested in oscillatory). Antibody 10E5 was a potent inhibitor (laminar less than 1%, P less than .0001, oscillatory less than 1.6%, P less than .01) of platelet deposition in both systems, and in this case, true adhesion (first attached layer) was blocked. Antibody 6D1 unexpectedly inhibited 70% of platelet deposition (P less than .01) in steady laminar flow and 56.5% in oscillatory flow (P less than .01). Scanning electron microscopy demonstrated platelets atop platelets in the controls, rare platelets in the 10E5 group, and a patchy monolayer of platelets in the 6D1 group. Transmission electron microscopy of cross-sections confirmed these observations. We conclude that the adhesion of the first platelet layer to an artificial surface requires GPIIb/IIIa. The data also suggest that GPIb is required for the development of the second layer in vertical platelet thrombus growth. PMID- 1859883 TI - High doses of intravenous immunoglobulin do not affect the recognition phase of the classical complement pathway. AB - We have recently found that intravenous immunoglobulin (IVIg) prevents deposition of C3 and C4 fragments onto antibody sensitized erythrocytes. To find out if such an effect results from the blockade of the recognition phase of the classical complement cascade, we investigated the ability of human serum containing high concentrations of IVIg to deposit the recognition subunit of the first complement component (C1q) onto targets. Normal human serum supplemented in vitro with IVIg did not demonstrate reduced C1q binding to targets as determined by radiolabeled antihuman C1q antibody uptake. Similarly, methylamine-treated normal human serum to which IVIg was added was equally effective in terms of C1q binding as the same serum without IVIg. At increasing doses of sensitizing antibody, C1q uptake decreased proportionally; however, at all antibody dilution points C1q uptake was not significantly different in the serum with IVIg in comparison with normal serum. Serum from a patient treated with IVIg did not differ in its capacity to deposit C1q from the same patient's serum before therapy. Our data suggest that IVIg does not interfere with the recognition step of classical complement pathway. This is a US government work. There are no restrictions on its use. PMID- 1859884 TI - Expression of interleukin-4 receptors on early human B-lineage cells. AB - Interleukin-4 (IL-4) regulates multiple stages of the antigen-dependent phase of B-cell development. However, its precise role in regulating B lymphopoiesis in bone marrow is not as well defined. We examined whether surface IgM- normal and leukemic human B-cell precursors (BCP) expressed IL-4 receptors using biotinylated IL-4. Constitutive expression of IL-4 receptors was detected on both normal and leukemic BCP. A higher percentage of normal BCP (82% +/- 15%) expressed IL-4 receptors compared with leukemic BCP (44% +/- 8%). Using mean fluorescent intensity as an indicator of receptor level on the IL-4 receptor positive cells, normal (91 +/- 41) and leukemic (44 +/- 37) BCP expressed comparable numbers of receptors. IL-4 induced the expression of CD23 on 30% of the leukemic BCP cases examined. IL-4 induced CD23 on surface IgM+ fetal bone marrow lymphoid cells but not on the surface IgM- normal BCP, despite the presence of detectable receptors on the surface IgM- cells. IL-4 did not stimulate proliferation of normal BCP, nor could it enhance the effect of recombinant IL-7 or low molecular weight B-cell growth factor. However, IL-4 increased the expression of surface IgM and surface Ig kappa on in vitro differentiated pre-B cells. Our collective results identify no role for IL-4 in the proliferation of normal or leukemic BCP, but identify a role in the enhancement of surface Ig expression during pre-B to B-cell differentiation. PMID- 1859885 TI - Detection of lymphomatous bone marrow involvement with magnetic resonance imaging. AB - We reviewed magnetic resonance (MR) staging examinations of 98 patients with malignant lymphoma who failed other therapy and were under evaluation for bone marrow transplantation. MR scan results were compared with blind posterior iliac crest aspirations and biopsies. Images of vertebral, pelvic, and femoral marrow were obtained using a standard T1-weighted, short repetition time (TR), short time to echo (TE) (TR700/TE22), spin-echo (T1-SE) method in 92 patients and short TI inversion recovery (STIR) technique (TR1,500/TE36/TI100) in all. On standard T1-SE sequence, normal marrow is bright due to the predominance of marrow fat, and tumor is dark. With STIR images, water containing tumor has a very high signal intensity in a dark (fat suppressed) background. Thirteen patients had positive MR scans and marrow biopsies, whereas 49 had negative MR scans and biopsies. Of 36 discordant MR/histology results, 10 had positive biopsies and negative MR exams; eight of these had microscopic infiltration (less than or equal to 5%) with tumor. MR detected marrow tumor either in the crests or elsewhere in 25 of 75 (33%) patients with negative study biopsies. We could confirm marrow involvement in 15 of these 25 (60%) by clinical methods. Therefore, up to one third of the patients evaluated with routine biopsies may have occult marrow tumor detectable by MR exam. In patients with negative marrow biopsies, especially those with Hodgkin's disease or intermediate to high-grade non-Hodgkin's lymphomas, MR scans found focal lesions distant from the crests. Biopsy better detected lower grade microscopic involvement. We conclude that optimal marrow staging of lymphoma patients incorporates both biopsy and MR imaging. PMID- 1859886 TI - Detection of minimal residual disease in T-cell acute lymphoblastic leukemia using polymerase chain reaction predicts impending relapse. AB - After achieving remission, approximately one-third of patients with T-cell acute lymphoblastic leukemia (T-ALL) relapse due to the resurgence of residual leukemic cells that cannot be detected in remission by morphologic methods. Thus, the early detection of residual disease is highly desirable to monitor the efficacy of therapy, or to institute an alternative mode of therapy. Toward this aim, we have examined the applicability of polymerase chain reaction (PCR) amplification in the detection of minimal residual disease (MRD) in bone marrow samples from patients with T-ALL in morphologic remission. Two different approaches were taken to identify leukemic clone-specific sequences that could be used as targets for PCR amplification. The first technique used T-cell receptor-delta (TCR-delta) gene rearrangements that were sequenced directly after PCR amplification of leukemic DNA. This method was successful in generating clone-specific probes for 76% of T-ALL patients screened. An alternative method was used to clone and sequence a TCR-beta chain gene from leukemic cells to generate a specific probe. The PCR assays that we used were specific for each patient's leukemic clone, and were capable of routinely detecting one leukemic cell in 10(4) normal cells. Using these sensitive PCR-based assays, we found no evidence for persistence of the leukemic clone in any of the bone marrow samples from four T-ALL patients who are in long-term (3.9 + to 8.1 + years) remission. In contrast, we detected residual disease in clinical remission samples from two patients who subsequently relapsed. In one patient, where we had appropriate samples, we observed a dramatic expansion of the leukemic clone 3 months before clinical relapse. These results suggest that PCR-based assays for detection of MRD in T-ALL patients have great potential in predicting impending relapse, and in determining the efficacy of the anti-leukemic therapy. These methods may also allow the identification of long-term survivors. PMID- 1859887 TI - The t(1;22) (p13;q13) is nonrandom and restricted to infants with acute megakaryoblastic leukemia: a Pediatric Oncology Group Study. AB - We report the nonrandom occurrence and frequency of the t(1;22)(p13;q13) in acute myeloid leukemia (AML) and its close association with the French-American-British M7 subtype of AML in infants (less than 1 year). This chromosomal abnormality occurred in 6 of 252 (2.4%) children and adolescents with AML (6 of 28 infants, 22%; 6 of 18 M7 AML cases overall, 33%; and 6 of 6 M7 cases in infants). Infants with AML of M7 subtype and the t(1;22) often presented with prominent abdominal masses. Two of these infants were not treated and died early. Three of four treated infants entered complete remission with therapy for AML; the remaining infant died of hemorrhage on day 8. Of the three infants who entered remission, only one remains alive and disease free at 5+ months. The other two infants relapsed in the bone marrow at 5 and 2 months from the start of therapy, respectively. We conclude that M7 AML with the t(1;22) usually presents in infants with extensive infiltration of abdominal organs by leukemic cells and may confer a poor prognosis despite intensive AML-directed treatment. Identification of this nonrandom translocation exclusively in infants with acute megakaryoblastic leukemia (AMkL) implies that it may serve as an additional diagnostic marker for this disease and links it to the pathogenesis of AMkL in infants. PMID- 1859889 TI - Acute leukemia after a primary myelodysplastic syndrome: immunophenotypic, genotypic, and clinical characteristics. AB - We studied the nature of blast cells in 41 patients with acute leukemia following a previous primary myelodysplastic syndrome (MDS) by a combined multiparameter analysis including morphologic, immunophenotypic, and molecular genetic (Igs, T cell receptor (TCR)-beta, -gamma, and -delta and the major breakpoint cluster region [M-bcr]) investigations. In addition, the clinical and hematologic characteristics according to the immunophenotype of blast cells were analyzed. Our results show that, although the granulocytic and/or monocytic lineages are those most commonly involved in these acute leukemias, other cell components, including the megakaryocytic and lymphoid, may be present (12% and 15% of the cases, respectively). Moreover, both morphologic and phenotypic studies show the frequent coexistence of two or three cell populations. Interestingly, in all cases the lymphoblastic component constantly displayed an early B phenotype (CD19+, CD10-, TdT+). Upon analyzing whether the type of MDS conditioned any differences in the immunophenotype of blast cells, we observed that, although the lymphoid lineage may be involved in all MDS subgroups, some differences emerge within the myeloid leukemic transformations. Thus, the refractory anemias with excess of blasts (RAEB) and RAEB in transformation displayed a significantly higher incidence of myeloblastic and megakaryoblastic transformations, while in the RA, RA with ring sideroblasts and chronic myelomonocytic leukemia, the granulo-monocytic phenotype predominated. In addition, our results show that the clinical and hematologic characteristics of these patients may be partially related to the immunophenotype of the blast cells. Ig heavy chain gene rearrangements were found in two of 19 patients analyzed (11%), one with a hybrid leukemia (lymphoid-myeloid) and the other with a granulo-monocytic phenotype. Two other hybrid transformations analyzed were in germline configuration. Gamma and delta gene rearrangements were found in 21% and 37% of these acute transformation, respectively. The TCR-beta and M-bcr were in germline configuration in all 19 cases studied. In summary, immunophenotype and molecular studies point to a pluripotent stem cell with preferential myeloid commitment as the target cell of leukemias following a primary MDS. PMID- 1859888 TI - Human interleukin-7 induces proliferation of neoplastic cells from chronic lymphocytic leukemia and acute leukemias. AB - The biologic effects of interleukin-7 (IL-7) and the expression of specific IL-7 membrane receptors on isolated neoplastic cells from previously untreated patients with chronic lymphocytic leukemia as well as acute leukemias were investigated in vitro. Leukemic cells were incubated for up to 6 days with various concentrations of IL-7 (0.01 to 2,000 U/mL). Neoplastic cells of the T- or B-phenotype from chronic as well as from acute leukemias proliferated in a dose-dependent manner. Cells from acute myeloid leukemias also proliferated in response to IL-7. An optimal proliferative effect was achieved between 96 and 120 hours with 200 U/mL IL-7. Combinations of IL-7 with IL-2 and tumor necrosis factor-alpha showed an additive effect on [3H]TdR incorporation. IL-7 binding assays gave a value of approximately 33 to 180 high-affinity (kd approximately 20 pmol/L) binding sites/cell and approximately 241 to 3,280 low-affinity (kd approximately 600 pmol/L) binding sites/cell. Receptor expression correlated with the proliferation in response to IL-7. These data indicate that IL-7 can induce proliferation of relatively mature tumor cells, and that this effect is not restricted to the lymphoid lineage. PMID- 1859890 TI - Trisomy 12 in chronic lymphocytic leukemia: an interphase cytogenetic study. AB - Interphase cytogenetics by means of in situ hybridization with the chromosome 12 specific biotinylated alpha satellite DNA probe pSP 12-1 was used for the study of trisomy 12, the most common chromosomal abnormality in chronic lymphocytic leukemia. In situ hybridization was performed on methanol/acetic acid fixed cells of conventional cytogenetic preparations from eight patients and on morphologically and immunologically classified cells of cytospin preparations from seven patients. The results show that trisomy 12 is more common than assumed on the basis of karyotype analysis of metaphase chromosomes: 2 of 13 patients with a normal karyotype in G-banding analysis were shown to have trisomy 12 by interphase cytogenetics. Immunophenotyping of the cells of one patient showed that the trisomy was restricted to cells with Ig light chain clonality. For the evaluation of the prognostic, therapeutic, and biologic significance of trisomy 12, in situ hybridization should be used in parallel with karyotype analysis because it allows the study of all cell populations of both interphase and mitotic cells, whether neoplastic or normal. PMID- 1859891 TI - Activation of platelet heparitinase by tumor cell-derived factors. AB - The nature of the cooperation between platelets and tumor cells during the process of blood-borne metastasis is essentially unknown. In previous in vitro studies we showed that platelets participated in the formation of gaps in the endothelial cell lining, and that concomitantly heparan sulfate glycosaminoglycans were degraded by the platelet heparitinase, released on activation of platelets. In the current study we show that the ability to degrade proteoheparan sulfate derived from endothelial extracellular matrix is gradually eliminated when the number of human platelets is decreased from 5 x 10(7) to 10(6) cells/mL. When aliquots of conditioned media or lysates of either Eb or heat-inactivated ESb mouse lymphoma cells (both of which showed no heparanase activity) were added to freeze-thawed lysates of 10(6) platelets, a reappearance of platelet heparitinase activity was observed. A similar activation was not elicited by lysates of several normal mammalian cells. These data suggest that in its native form, a fraction of the platelet heparitinase is stored in an inactive form that can be activated by a factor secreted by lymphoma, but not by normal cells. Partial characterization of the heparitinase-activating factor showed that it is a heat-stable polyanionic molecule, devoid of proteolytic activity and resistant to both proteolytic and chondroitinase digestions. Activation of platelet heparitinase was also observed on coincubation with chondroitinases ABC and AC, suggesting that the inactive form of platelet heparitinase could result from a complex formation with a chondroitinase-sensitive proteoglycan. The lymphoma-derived heparitinase activating factor itself is, however, not a chondroitinase, because activity of chondroitinase could not be detected in Eb and ESb cells. A possible mechanism by which tumor cells recruit and regulate the activity of platelet heparitinase, and its relevance to the progression of blood borne metastasis, is discussed. PMID- 1859892 TI - Emergence of a B-cell lymphoblastic lymphoma in a patient with B-cell chronic lymphocytic leukemia: evidence for the single-cell origin of the two tumors. AB - A patient is described who presented with a chronic lymphocytic leukemia (CLL) and later developed a lymphoblastic lymphoma. The cells from the CLL were typical mature B lymphocytes as could be assessed by morphologic, cytochemical, and surface marker analyses. The cells from the lymphoblastic lymphoma were immature B cells that expressed CD10, CD20, and HLA-DR markers, but not surface Ig or cytoplasmic mu chains, and were negative for terminal deoxynucleotidyl transferase (TdT). The cells of two continuous cell lines, obtained from the bone marrow and the peripheral blood of the patient, had the same phenotype as the lymphoblastic lymphoma cells, did not contain the Epstein-Barr virus genome, and displayed malignant features in vitro, including the capacity to form colonies in agar. The two cell lines also shared identical chromosomal abnormalities, a finding which suggests that they derived from the same malignant cell already present in vivo. Such chromosomal abnormalities were not seen in the karyotype of the peripheral blood cells at the onset of the disease. Analysis of the Ig heavy chain genes using a DJ-specific probe showed the very same monoclonal rearrangement in the cells from the B-CLL, the lymphoblastic lymphoma and the two cell lines, thus demonstrating their common clonal origin. By contrast, a monoclonal rearrangement of the lambda chain gene locus was found in the B-CLL cells only, a finding consistent with their exclusive capacity to express surface IgM lambda. This patient represents a rare case in whom a chronic lymphoproliferative disorder with mature malignant cells transforms into a lymphoblastic lymphoma characterized by cells frozen at a very early maturational stage. The possible mechanisms leading to such transformation within the same cell clone are discussed. PMID- 1859893 TI - Rosetting of Plasmodium falciparum-infected red blood cells with uninfected red blood cells enhances microvascular obstruction under flow conditions. AB - The occurrence of rosetting of Plasmodium falciparum-infected human red blood cells (IRBC) with uninfected red blood cells (RBC) and its potential pathophysiologic consequences were investigated under flow conditions using the perfused rat mesocecum vasculature. Perfusion experiments were performed using two knobby (K+) lines of P falciparum, ie, rosetting positive (K+R+) and rosetting negative (K+R-). The infusion of K+R+ IRBC resulted in higher peripheral resistance (PRU) than K+R- IRBC (P less than .0012). Video microscopy showed that under conditions of flow, in addition to cytoadherence of K+R+ IRBC to the venular endothelium, rosette formation was also restricted to venules, especially in the areas of slow flow. Rosettes were absent in arterioles and were presumably dissociated by higher wall shear rates. The presence of rosettes in the venules must therefore reflect their rapid reformation after disruption. Cytoadherence of K+R+ IRBC was characterized by formation of focal clusters along the venular wall. In addition, large aggregates of RBC were frequently observed at venular junctions, probably as a result of interaction between flowing rosettes, free IRBC, and uninfected RBC. In contrast, the infusion of K+R+ IRBC resulted in diffuse cytoadherence of these cells exclusively to the venular endothelium but not in rosetting or large aggregate formation. The cytoadherence of K+R+ IRBC showed strong inverse correlation with the venular diameter (r = .856, P less than .00001). Incubation of K+R+ IRBC with heparin and with monoclonal antibodies to glycoprotein IV/CD36 abolished the rosette formation and resulted in decreased PRU and microvascular blockage. These findings demonstrate that rosetting of K+R+ IRBC with uninfected RBC enhances vasocclusion, suggesting an important in vivo role for rosetting in the microvascular sequestration of P falciparum-infected RBC. PMID- 1859894 TI - Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for relapsed non-Hodgkin's lymphoma: blood and bone marrow progenitor growth studies. A phase II Eastern Cooperative Oncology Group Trial. AB - Sixteen patients with relapsed non-Hodgkin's lymphoma underwent autologous bone marrow transplantation and infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Treatment consisted of involved-field radiotherapy, cyclophosphamide 60 mg/kg/d intravenously (IV) for 2 days, and fractionated total body irradiation (1,200 cGy). Autologous bone marrow was thawed and infused IV, followed 3 hours later by the first infusion of IV rhGM CSF 11 micrograms/kg/d over 4 hours. Infusions of rhGM-CSF were continued daily until either both neutrophil count exceeded 1,500/microL and platelet count exceeded 50,000/microL, or until 30 days after marrow re-infusion. Toxicities encountered were mild and included fever, chills, hypertension, alopecia, rash, diarrhea, stomatitis, myalgias, and synovial (knee) effusions. Neutrophil recovery greater than 500/microL occurred a median of 14 days (range, 9 to 30 days) after marrow infusion, significantly earlier than in a comparable group of historic controls who recovered counts at a median time of 20 days (range, 12 to 51 days) (P = .00002). Median time to self-sustaining platelet counts greater than 20,000/microL was 23.5 days (range, 12 to 100 days), comparable with the historic group (P = .38). One bacteremia (central venous catheter exit site infection with Staphylococcus epidermidis) and one local infection (Giardia lamblia in stool) occurred. Patients received a median of 11.4 (range, 4.4 to 20.2) x 10(4) colony-forming unit granulocyte-macrophage (CFU-GM) progenitors per kg. Stem cell progenitors CFU-GM, CFU-granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM), and burst-forming unit-erythroid (BFU-E) were detected in the bone marrow as early as 7 days after marrow re-infusion, and increased in proportion to peripheral blood counts, but by 30 to 60 days still remained much lower than before transplant. Neutrophils transiently decreased in 13 of 16 patients (median decrease, 42%) within 24 to 72 hours of discontinuing rhGM-CSF infusions. These data suggest that rhGM-CSF therapy enhances neutrophil recovery by forcing stem cells to produce mature elements at an enhanced rate but may not affect marrow stem cell and early progenitor population sizes. PMID- 1859896 TI - Interleukin-1 beta expression and treatment outcome in acute myelogenous leukemia. PMID- 1859895 TI - Treatment for acute myelocytic leukemia with allogeneic bone marrow transplantation following preparation with BuCy2. AB - One hundred twenty-seven patients with acute myelocytic leukemia (AML) were given busulfan 4 mg/kg on each of 4 days and cyclophosphamide 60 mg/kg on each of 2 days (BuCy2) followed by allogeneic bone marrow transplantation from an HLA identical or one antigen disparate sibling. For 71 patients in first complete remission, 23 in second complete remission or initial relapse, and 33 patients with primary refractory disease, second or subsequent relapse, or a preceding hematologic disorder, the 3-year leukemia-free survival (LFS) is 63.1%, 32.6%, and 24.2% respectively. The actuarial probability of relapse for each group is 14.1%, 40.6%, and 61.0%. In multivariate analyses, relapse and decreased LFS were associated with advanced disease phase and with M4/M5 French-American-British classification. The LFS of first remission patients was adversely associated with a short time interval from diagnosis to transplantation. This study indicates that BuCy2 is an attractive preparative regimen for marrow transplantation in patients with AML and that prognostic factors for relapse and LFS are similar those described for regimens containing total body irradiation. PMID- 1859897 TI - Human T-lymphotropic virus type I: new risk for Chilean population. PMID- 1859899 TI - [Evolution of cancer mortality. Reflexions of a physician]. AB - Changes in cancer mortality trends in Europe and the USA are correlated with changes in the environment. Active prevention by means of antioxidants and antiproliferative agents etc should be used more extensively and advertisements regarding tobacco habits should rely more on methods intended to project a negative image of smokers. At the present time, anticancer therapies lengthen the survival of patients, which could induce bias in statistics. In the future it seems likely that they will play a greater role against cancer than early detection. Nevertheless, efforts should be made in this direction, at least with regard to young people due to the decreasing mean age of the appearance of several tumors. PMID- 1859898 TI - Rapid diagnosis of alpha-thalassemia-1 of southeast Asia type and hydrops fetalis by polymerase chain reaction. PMID- 1859900 TI - [Observance in cancerology]. PMID- 1859901 TI - [Incidence, diagnosis, treatment and prognosis of cancer of the pancreas: development in Cote-d'Or from 1976 to 1985]. AB - The aim of this study was to analyze the epidemiological aspects of pancreatic cancers and their time trends in the Cote-d'Or population between 1976 and 1985. Over a period of ten years, 444 cases were diagnosed. The incidence rates standardized according to the world reference population were 8.2/100,000 in males and 3.8/100,000 in females. The Cote-d'Or is an intermediate risk area for pancreatic cancer. This cancer was slightly more common in urban than in rural areas (NS). The initially urban predominance of pancreatic cancer in males was no longer present 10 years later. Between 1976 and 1985, incidence of pancreatic cancer decreased by a mean of 4.7% per year in males (NS) and 0.5% per year in females (NS). A high proportion of the cancers (73.9%) were located in the head of the pancreas; among histologically confirmed cases, 69.7% were adenocarcinomas. Criteria for diagnosis evolved throughout the 10 years. The rate of histological confirmation increased annually by a mean of 3.0% (P less than 0.001). The relative importance among diagnostic procedures of direct biliary and pancreatic examinations decreased (P less than 0.05) whereas that of ultrasonography and radioscan increased (P less than 0.001). The overall surgical rate was 64.4% and the rate of curative surgery was 4.4%. The operability rate increased annually by a mean of 2.0% (NS). The overall survival rate was 13.2% after 1 year, 4.5% after 3 years and 3.2% after 5 years. Prognosis depended neither on age nor on sex or cancer location. The 5-year survival rate was 38.5% in the limited group of patients (n = 13) who underwent surgery for cure, and 0.0% in patients with palliative treatment. These data emphasize the severity of pancreatic cancers and the absence of any therapeutical improvement between 1976 and 1985 in spite of the evolution in diagnostic procedures. PMID- 1859903 TI - [Oral contraception and benign breast diseases: point of view of the epidemiologist]. AB - The study of the association between oral contraceptives (OC) and benign breast disease (BBD) is of great interest for the epidemiologist, because of the impact that this association may have on the risk of breast cancer. In fact, three factors have to be analysed simultaneously: OC use, the occurrence of BBD and the occurrence of breast cancer. This analysis is complex because two out of the three factors are not univocal in their definition (various composition and doses for pills, numerous histologic types of BBD). Moreover, a fourth parameter is to take into account: the time factor. This last factor intervenes in the chronological order of events (OC before or after BBD), and for the use of different types of pills (duration of use, age at the start of OC use before or after the first full-term pregnancy, etc). Although all the relationships between these different factors are still insufficiently known at the present time, certain points are acquired: 1) OC use decreases the risk of BBD (particularly when pills contain high doses of progestogens); 2) a history of BBD increases the risk of breast cancer (particularly when BBD is a fibrocystic mastosis with cellular atypia); 3) in spite of the decrease in the risk of BBD associated with OC use, OC use does not decrease the risk of breast cancer. For a long time, this third proposition appeared as paradoxal. In 1986, Stadel and Schlesselman tried to estimate the terms of this paradoxe. Their estimations allowed to show that the risk of breast cancer associated with OC use, for women with a history of BBD, was overestimated in all previous reports. Indeed, the decrease of the occurrence of BBD due to OC use, which was associated with an important reduction in the number of breast cancer cases, was not taken into account in the estimation of this risk. Other epidemiological investigations with a greater number of subjects are needed to further analyse complex relationships between OC use, BBD and breast cancer. PMID- 1859902 TI - [Brain metastases of malignant melanomas]. AB - Cerebral metastases of malignant melanoma are correlated with a very poor prognosis. Surgery of an isolated metastase can lead to a long survival but the brain lesions are frequently numerous and associated with an extracerebral diffusion. Dacarbazine (DTIC) gives a mean response rate of 21% on visceral localisations but doesn't cross the blood brain barrier (BBB). Neither do the biological response modifiers like Interleukin 2 (Il2) that leads to 25% response rate in disseminated melanoma. Nitrosoureas like carmustine (BCNU) and semustine (CCNU) have been investigated in different non randomised studies and the clinical results didn't illustrate their theorical ability to cross the BBB. Radiotherapy is also used as a palliative therapy with 7 to 16 weeks survival. Fotemustine (muphoran), a new amino acid linked nitrosourea, can give a response rate up to 28.2% in patients with cerebral metastases and the increased survival of responding patients is significant. The availability of this new drug may suggest associations with surgery and radiotherapy in the future to improve the survival of such patients. PMID- 1859904 TI - [Hormone treatment of benign breast diseases]. PMID- 1859905 TI - [Treatment of postoperative lymphedema of the upper limb]. AB - In breast cancer the overall incidence of post-therapeutic lymphedemas of the arm remains at 20% despite the use of new conservative treatments. Patients suffering from pains and heaviness require additional treatment for their swollen arm. One hundred and seventy-nine women with a post therapeutic edema of the upper limb have been treated in a special medical unit where medical and physiotherapeutic care were given as an intensive treatment for 4 weeks. More than 80% of good results were obtained with a median decrease in volume of swelling of 45%. The duration of the clinical improvement during the 6 months following the intensive first treatment was excellent for 76% of all improved cases. Treatment failure occurred in 16.2% of upper limb swelling mostly in relation to a recurrence of the disease (81%). 84.3% of cases undergoing a second intensive treatment 6 months later displayed a new decrease in volume and a new real clinical improvement. Small post therapeutic lymphedemas must be treated as soon as possible to avoid more serious delayed disorders. PMID- 1859906 TI - Adjuvant endocrine therapy for operable breast cancer. AB - A brief resume of adjuvant endocrine therapy for operable breast cancer is given. This was first suggested in the 1930's but has only become accepted in the last 10-15 years. The reason for the lack of survival benefit in the first randomised trial, which began in 1948 in Manchester, was thought to be due to the increasing use of hormone therapy for metastases. Revival of interest came with the survival gain reported in the Toronto ovarian trial and the success in post-menopausal patients of the non-toxic anti-oestrogen tamoxifen. The different dose schedules used in the various large tamoxifen trials could explain the confusingly variable results in the literature. Combined analysis of trial results indicates that CMF is the adjuvant therapy of choice for pre-menopausal patients but this therapy may in part be acting through the ovaries. The Scottish and NATO trials have an overall survival advantage from adjuvant tamoxifen, even in pre-menopausal patients, and both have shown results to be independent of oestrogen receptor (ER) status. Whether the extra 3 years given in Scotland adds an additional benefit over the more commonly used 2-year course is uncertain. A statistically invalid look at selected data in the Scottish trial suggests that, in ER positive cases, post-relapse tamoxifen may have as great an effect on total survival as adjuvant use, a finding similar to that suggested by the first ovarian ablation trial and one requiring continued review. PMID- 1859908 TI - Future directions in tobacco research. PMID- 1859907 TI - The tobacco habit as drug dependence. PMID- 1859909 TI - Implications of tobacco use as an addiction. PMID- 1859910 TI - The influence of stress on psychopharmacological responses to nicotine. AB - This essay considers the mechanisms which may mediate the apparent anxiolytic properties of nicotine and which are thought to be responsible for the 'calming' effect of tobacco smoke experienced by many smokers. It summarizes the evidence that, in many tests for anxiolytic activity, the effects of nicotine do not resemble those of established anxiolytic drugs such as diazepam and concludes that it is likely that neural systems other than those which mediate the responses to the benzodiazepines are responsible for the putative anxiolytic properties of nicotine. Circumstantial evidence which suggests that the increase in mesolimbic dopamine secretion evoked by nicotine may not only be rewarding per se but may also contribute to the ability of the drug to alleviate the effects of stress is presented. The essay also summarizes results which suggest that chronic nicotine evokes changes in the mesolimbic dopamine system which resemble those seen in animals treated chronically with antidepressant drugs and proposes that the mechanisms which mediate the ability of antidepressant drugs to alleviate the effects of stress may also mediate the apparent anxiolytic properties of nicotine. The possible consequences of this hypothesis for future research are considered. PMID- 1859911 TI - Pharmacodynamics of nicotine: implications for rational treatment of nicotine addiction. AB - Rational treatment of the pharmacologic aspects of tobacco addiction includes nicotine substitution therapy. Understanding the pharmacodynamics of nicotine and its role in the addiction process provides a basis for rational therapeutic intervention. Pharmacodynamic considerations are discussed in relation to the elements of smoking cessation therapy: setting objectives, selecting appropriate medication and dosing form, selecting the optimal doses and dosage regimens, assessing therapeutic outcome, and adjusting therapy to optimize benefits and minimize risks. PMID- 1859912 TI - Nicotinic receptor blockade therapy and smoking cessation. AB - Smoking is a behaviour with a significant conditioned component. Attempts to quit will likely fail unless the effects of primary and secondary reinforcers are extinguished. Current smoking cessation methods scarcely address this issue, which may explain why they meet with little success in the long term. In contrast, the administration of centrally-active nicotinic receptor antagonists should provide a means of extinguishing both primary and secondary reinforcers associated with smoking. Thus, nicotine blockade therapy presents a promising new approach to smoking cessation. PMID- 1859913 TI - Understanding brain mechanisms in nicotine reinforcement. AB - Current understanding of the mechanisms through which nicotine acts to reinforce behavior is limited. Demonstrated interactions between nicotine and the mesolimbic dopamine system have provided the impetus for investigations of the role of this particular brain pathway in nicotine reinforcement, and preliminary studies do indeed suggest that the dopamine system might be involved in self administration of nicotine. However, there are clearly other possible brain sites and neurotransmitter mechanisms that could be critical to reinforcement processes for nicotine. This article proposes that a broadly-based attack on the question of nicotine reinforcement would be the most fruitful; basic biological research should aim to verify the involvement of the mesolimbic dopamine system, but also to elucidate other candidate brain systems that may contribute to the reinforcing properties of nicotine. PMID- 1859914 TI - Rehabilitating a genetic perspective in the study of tobacco and alcohol use. AB - Despite comparable estimates of 'heritability' for tobacco smoking and alcohol drinking, the human genetics of drinking has been a fashionable topic for research, while the human genetics of smoking has been neglected or viewed with suspicion. The differing course of genetic themes in the alcohol and tobacco areas is discussed in relation to (a) different historical pressures which promoted disease models of alcoholism and 'bad habit' models of heavy smoking and (b) possible fundamental differences in the nature of cigarette and alcohol use. This topic is further complicated by the substantial co-occurrence of heavy smoking and heavy drinking, so that the genetic determinants may well over-lap. 'Cross-cultural' comparison of these contrasting interests in genetics is argued to be an important topic for future research. PMID- 1859915 TI - Biobehavioral research on nicotine use in women. AB - More American women are taking up smoking than men and fewer are quitting; if current trends continue, rates for women will surpass those for men by the mid 1990's. But ironically, much of what is known about the biobehavioural aspects of smoking is based on research using male subjects. The present paper reviews evidence suggesting that: (1) women may differ from men with regard to nicotine intake and/or effects; (2) nicotine intake and effects may be influenced by menstrual cycle phase; (3) oral contraceptive use and estrogen replacement therapy may affect intake and effects of nicotine; (4) the effects of chronic nicotine use on female reproductive endocrinology may have implications for the reinforcement of smoking; and (5) pharmacological agents used to treat smoking may have different effects in women than in men. Guidelines and suggestions are presented by future biobehavioural research in women, including standardization of assessment procedures, attention to the use of appropriate controls, and use of pharmacological probes. PMID- 1859916 TI - Towards better diagnoses and more individual treatment of tobacco dependence. AB - The nicotine dependence concept is well founded and it is clear that it is necessary to assess this before treatment starts. Behavioural dependence, although difficult to disentangle from the pharmacological dependence, is also important. With the development of tools for assessing behavioural dependence, the behavioural treatment methods could be applied to patients more appropriately. The place of new drugs such as clonidine and antidepressants is also discussed. It is suggested that some of the nicotine withdrawal syndrome may have similarities with hypoglycemia and increased eating after stopping smoking may be a form of self-medication. Lastly, the new forms of giving nicotine replacement are put in perspective. PMID- 1859917 TI - Smoking and smoking cessation in cancer patients. AB - Persons with malignant disease have been a neglected population for research in smoking cessation. Besides the well-established role of cigarette smoking in the development of several types of cancers, there are numerous adverse health consequences of continued smoking for the diagnosed cancer patient. These include: increased risk of further neoplasms, poorer survival, and complications of surgery, radiation and chemotherapy; risk of non-neoplastic smoking-related diseases; and additional impairment of appetite and nutrition. Smoking prevalence at diagnosis is highest among patients with smoking-related cancers. Prospective studies of a variety of cancer patient populations are needed to assess patterns of continued smoking and cessation. Systematic quit smoking programs should be integrated into cancer treatment regimens. Currently, two trials testing interventions delivered by medical providers are in progress. Important research issues concerning intervention in cancer patient smoking behavior include: identification of relevant target groups; definition of intervention style and content; delineation of dimensions of treatment; and documentation of beneficial effects. The growing number of long-term cancer survivors and the complications from other smoking-related diseases dictate that the smoking cessation needs of this population be addressed. PMID- 1859919 TI - Smokeless tobacco: current status and future directions. AB - Smokeless tobacco is addicting, can cause physical dependence, and is associated with many health risks. In spite of these concerns over its use, minimal research has been conducted to understand the effects from and factors associated with smokeless tobacco use. Additionally, relatively few studies have examined potentially effective treatments for the smokeless tobacco user. This paper reviews the existing literature in this area and considers future directions for research. PMID- 1859918 TI - Individual differences in difficulty quitting smoking. AB - This essay comments on the main approaches to studying individual differences in ability to quit smoking, and suggests complementing them with a concept of 'difficulty of quitting'. Several areas of research into determinants of ability to quit smoking are discussed, including measures of dependence, reactivity to nicotine, severity of withdrawal symptoms, endurance of discomfort, and psychological well being. A number of correlates of inability to quit may have a common denominator in stress and neuroticism. If these are the primary obstacles to quitting, changes in the composition of the smoking population and in the image of smoking can be expected which could lead to smoking losing some of its appeal for potential new recruits. PMID- 1859920 TI - Is nicotine more addictive than cocaine? AB - Is nicotine more addictive than cocaine? That claim is increasingly in vogue, often supported by data showing the high likelihood of progression to daily tobacco use following experimentation and the high percentage of cigarette smokers, compared with cocaine users who appear addicted. In the context of criteria for addiction of dependence presented by the World Health Organization, the American Psychiatric Association, and the US Surgeon General, we consider several lines of evidence, including patterns of mortality, physical dependence potential, and pharmacologic addiction liability measures. Within each line of evidence, we compare nicotine with cocaine. We conclude that on the current evidence nicotine cannot be considered more addicting than cocaine. Both are highly addicting drugs for which patterns of use and the development of dependence are strongly influenced by factors such as availability, price, social pressures, and regulations, as well as certain pharmacologic characteristics. PMID- 1859921 TI - Beneficial effects of nicotine. AB - Nicotine in tobacco brings illness and death to millions of people. Yet nicotine in its pure form has the potential to be a valuable pharmaceutical agent. Nicotine fairly specifically binds to the cholinergic nicotinic gating site on cationic ion channels in receptors throughout the body. This action stimulates the release of a variety of neurotransmitters including especially catecholamines and serotonin. When chronically taken, nicotine may result in: (1) positive reinforcement, (2) negative reinforcement, (3) reduction of body weight, (4) enhancement of performance, and protection against; (5) Parkinson's disease (6) Tourette's disease (7) Alzheimers disease, (8) ulcerative colitis and (9) sleep apnea. The reliability of these effects varies greatly but justifies the search for more therapeutic applications for this interesting compound. PMID- 1859922 TI - Smoking cessation and weight gain. AB - Significant progress has been made in the research on smoking cessation and weight gain since the 1988 Surgeon General's Report, particularly on mechanisms and treatment methods. Smoking cessation results in weight gain in most quitters, primarily due to changes in caloric intake and to a lesser extent from changes in energy expenditure. Thus far, pharmacologic treatments appear more efficacious at preventing the weight gain than behavioral methods. And regarding who should receive treatment, preliminary research suggests that females are more concerned about postcessation weight gain than males, and it is the concern about weight gain--more than the weight gain itself--that appears to play an important role in relapse to smoking. Given the progress that has been made along the spectrum from mechanisms to treatment, those concerned about postcessation weight now have treatment options for preventing weight gain in the critical period immediately after smoking cessation. However, continued research into mechanisms, treatment methods, and individual differences will surely result in new and more effectively tailored treatment options. PMID- 1859923 TI - Smoking prevention: towards a process approach. AB - Current studies of smoking prevention treat the adolescent as a target of influence, they emphasize the acquisition of skills for resisting peer pressure and give too little attention to motivation for resistance. Studies consistent with this social learning framework show moderate reductions in the incidence of smoking for the short term; recent, long-term follow-ups show no reduction in experimental over control conditions. We propose a re-examination of the influence framework and suggest that adolescents use smoking and dress, to project an image of self that will increase the likelihood of success in the formation of relationships in which participants share feelings and attitudes toward each other and the adult world. We also suggest that adults focus upon external, perceptible, and remote threats, e.g. smoking is seen as evil, a response to peer pressure, and a long term threat to health, and ignore discourse about proximal, subjective feelings respecting the changing sexual urges and feelings of social anxiety that accompany adolescence. The socialization of these affects is left to the peer group. It is suggested that future programs intensify their focus on motivation for resisting smoking based upon a revised view of the adolescents objectives in self definition, and combine this with the best of the current skills approaches. PMID- 1859924 TI - The development of dependence on smoking in children. AB - The development of dependence on smoking has been largely unexplored and has theoretical importance and implications for interventions aimed at interrupting the early stages of smoking behaviour. Data are presented which indicate the importance of the first few cigarettes. The development of a regular smoking pattern had previously been reported to take about 2 years and involve a progression through a series of stages from smoking for psychosocial motives, to smoking for a positive nicotine effect and finally for some smokers, smoking to avoid withdrawal. Results from a small scale study with girls are described which give no support to the notion of any such well-defined stages in the novice smoker's career. Inhalation was apparent from early on indicating that nicotine can play an active role in reinforcing smoking from a very early stage. Furthermore, the majority of the young smokers perceived themselves to be dependent on their cigarettes. The nature of any positive reinforcement was unclear, the dependence-producing potential of smoking appearing to be largely due to relief of unpleasant feelings. These findings need to be replicated and the paper highlights other key areas in this field for future research. PMID- 1859925 TI - A bioinformational systems perspective on tobacco dependence. AB - Recent thinking about tobacco dependence has been influenced largely by a focus on the pharmacological effects of nicotine. We advocate a return to earlier views of dependence as comprising both pharmacological and non-pharmacological aspects. Moreover, we suggest that it may be profitable to reformulate research on dependence in terms of a bioinformational process model. The basic tenets of such a model are outlined, as are the challenges in exploring the nature of dependence simultaneously across the cognitive, physiological and behavioral domains of function. PMID- 1859926 TI - Research on stress and smoking: progress and problems. AB - Despite evidence that smoking behaviour increases in the context of stress, there has yet to be a clear-cut demonstration that nicotine intake is similarly enhanced. Although nicotine intake has been shown to reduce reported anxiety in the context of stress, the controlling conditions (type of stressor, intensity, temporal relationships, etc.) need further exploration. Recent findings involving nicotine's effects on the hypophyseal-adrenal axis provide a new perspective on these issues, in that increased nicotine intake during exposure to a stressor may represent, at least in part, behavioral compensation for diminished sensitivity to nicotine brought about by nicotine-stimulated corticosteroid release. Corticosteroids may decrease central nervous system excitability in a way that could account for anxiety reduction; on the other hand, anxiety reduction may be an epiphenomenon with respect to the reinforcement of smoking behaviour. The integration of behavioural, physiological, and biochemical research exemplified by the above approach should lead to a better understanding of stress and smoking. PMID- 1859927 TI - Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking. AB - Research on smoking cessation has increasingly focussed on pharmacological aspects of nicotine and nicotine withdrawal. However, cigarette smoking also provides a characteristic set of sensory cues. These sensory aspects of smoking are important to address in that they may be potent conditioned reinforcing stimuli linked to the actions of nicotine. The repetition of the smoking act thousands of times per year by a moderately heavy smoker leads to a strong conditioned association between the sensory aspects of smoking (the putative CS) and the pharmacological effects of nicotine (the putative UCS). Strategies for disrupting CS-UCS associations may be useful in developing more effective smoking cessation treatments. These include: counterconditioning of the CS; presenting the CS alone; presenting the CS with the UCS but pharmacologically blocking the UCS; and presenting the CS and UCS in an unconnected fashion. The role of sensory cues in alleviating craving for cigarettes is discussed, and specific techniques for duplicating relevant sensory aspects of smoking without delivering significant doses of nicotine are described. The combination of nicotine and nicotinic antagonists to block primary reinforcement and hasten extinction of conditioned reinforcement is also considered. PMID- 1859928 TI - Refining models of dependence: variations across persons and situations. AB - Having established that tobacco smoking is addictive, research should proceed to refine our models of dependence on nicotine and other drugs. Current theories of addiction do not account for between- or within-subjects variations in addictive behavior. Recent evidence that some people can smoke for decades without developing dependence demonstrates the potential for individual differences in vulnerability to dependence. Study of such anomalous smokers may provide insight into the mechanisms underlying nicotine dependence. Current theory and data also fail to provide adequate accounts of situational variation in addictive behavior and of the developmental progression from initial experimentation to dependence. PMID- 1859930 TI - Smoking and economic incentives in Europe. AB - This paper reviews the agenda for economic research near the beginning of a formative period for policy marked by much greater involvement by the EC (European Community). There are few signs as yet of any diffusion process at work in Europe to bring about reductions in smoking. Effective use of incentives will be needed to bring about reductions in smoking by 2000 and to stop yet further massive increases in mortality from smoking related disease. Research is needed on price and income elasticities in Europe as the EC introduces new policies for raising cigarette taxes and prices. Currently most estimates are based on US and UK data. There is also an important research agenda on the decision-making process in Europe covering the policy response of national governments and professions as well as the future role of the EC Commission. Finally, research is needed on the micro-economic determinants of the demand for tobacco products across Europe by households. Household data from family expenditure surveys are now available across Europe so that it is now possible to construct micro demand systems for each European country. PMID- 1859929 TI - The application of 1980s psychology to 1990s smoking research. AB - The 1988 Surgeon General's report (US DHHS, 1988) argued that smoking should be considered an addiction because it displays the features common to all addictive disorders, which were, most importantly, highly controlled or compulsive use of a psychoactive substance. Furthermore, urges to smoke were identified as directly responsible for this pattern of drug use. Although it is commonly asserted that urges are central to the addictive process, relatively little research has been devoted to this issue and the evidence that is available provides little support for the assumption. This paper argues that the role of urges in addictive smoking should receive greater attention from smoking researchers and offers several suggestions for overcoming the methodological and theoretical limitations of previous research on smoking urges. PMID- 1859931 TI - Comprehensive approaches to tobacco use control. AB - This essay suggests approaches to two issues of importance to the future of tobacco use control research. First, there is need to identify those areas of tobacco use prevention and cessation research which have evolved to the point where additional investigation would only bring incremental gains. The reduction potential of this research should then be consolidated by applying existing, effective interventions widely and systematically. Conversely, there is need to identify those areas in which additional research is necessary. Second, the most logical way to reach agreement on those areas which are ready to move from research to applications-of-research is, with the co-operation and advice of the research community, through the large funding organizations which have supported this research over the past 2 decades. It is these organizations which, once the most effective intervention are identified, are capable of supporting the centrally-planned, consensus-driven, comprehensive approaches to tobacco use control which will be necessary to continued success in reducing tobacco-related morbidity and mortality in the industralized world and to begin addressing the growing problems of tobacco use in the developing world. PMID- 1859932 TI - Conceptual and methodological considerations for tobacco addiction research. AB - The 1988 Surgeon General's Report on nicotine addiction has research and treatment implications. It focuses clinical treatments on tobacco use as an addiction and highlights the importance of examining actions of nicotine relevant to dependence. It also indicates the value of comparing the pharmacologic and behavioral processes underlying use of nicotine with other addictive drugs. This essay points out gaps that remain in our understanding of nicotine addiction. For example, the exact mechanisms underlying nicotine addiction are unknown. Also, the reasons for individual differences in initiation, withdrawal, relapse and reinforcing effects of tobacco use are not understood. Research designed to address these issues should be problem-driven and multidisciplinary. Parallel human and animal studies that include unconditioned as well as conditioned behaviors are particularly valuable. PMID- 1859933 TI - A time for conceptual stocktaking. AB - The Surgeon-General's report, by redefining the nature of the tobacco problem, invites a re-examination both of our goals and of our concepts and categories of tobacco use. A crucial pre-requisite to the acceptability of the development of refined nicotine-containing products, and of long-term nicotine maintenance therapy, will be progress in understanding the health risks of nicotine use per se. A broader conceptualization of prevalence and cessation is urged, one which takes account of cigar and pipe smoking as well as cigarettes. In addition to increasing overall prevalence somewhat, this approach drastically alters estimates of cessation rates, and indicates that the often-claimed gender difference in cessation is myth rather than reality. An analysis which combines social class and housing tenure as conjoint indicators of socio-economic position sharpens class gradients of smoking prevalence and shows that smokers are still comfortably in the majority among substantial groups of the population in the UK. Future progress in lowering prevalence, and hence smoking-related disease, is increasingly going to depend on reaching the most disadvantaged members of society. PMID- 1859934 TI - Toward a comprehensive strategy for reducing the health burden of tobacco. AB - In the absence of concerted worldwide action, the annual death toll from tobacco may reach 10 million by the middle of the next century. Smoking cessation approaches represent an important, but limited, means of reducing this death toll. Needed are co-ordinated strategies that address all facets of the tobacco issue. Especially important are advocacy campaigns targeting the tobacco industry and its supporters. Just as the Broad Street pump was isolated as the source of a cholera epidemic, the tobacco industry must be isolated as the source of a far greater epidemic. PMID- 1859935 TI - The future of nicotine replacement. AB - Following in the wake of progress forged by nicotine chewing gum, a new generation of nicotine replacement products will soon be available as aids to giving up smoking. These range from nicotine skin patches, which take 6-8 hrs to give very flat steady-state peak blood levels, to nicotine vapour inhalers which mimic the transient high-nicotine boli that follow within a few seconds of each inhaled puff of cigarette smoke. Other products undergoing clinical trials include a nasal nicotine spray and nicotine lozenges. It is argued here that it is not so much the efficacy of new nicotine delivery systems as temporary aids to cessation, but their potential as long-term alternatives to tobacco that makes the virtual elimination of tobacco a realistic future target. Their relative safety compared with tobacco is discussed. A case is advanced for selected nicotine replacement products to be made as palatable and acceptable as possible and actively promoted on the open market to enable them to compete with tobacco products. They will also need health authority endorsement, tax advantages and support from the anti-smoking movement if tobacco use is to be gradually phased out altogether. PMID- 1859936 TI - Great expectations: some suggestions for applying the balanced placebo design to nicotine and smoking. AB - There are a number of methodological problems with the traditional placebo controlled design used to investigate the effects of nicotine in human subjects. For example, the experimental instructions may create a 'guessing set' in the participants such that they search for possible clues to try to identify which condition they are in. If they guess correctly, the internal validity of the design may be threatened. Furthermore, by attempting to control for the effect of subjects' expectancies, the traditional placebo design precludes any estimate of expectancy effects. Continued use of this methodology in the smoking field is likely to lead to an overemphasis on pharmacological factors in smoking and a corresponding underemphasis on cognitive factors and nicotine-expectancy interactions. These problems can be overcome by the use of the balanced placebo design which orthogonally manipulates instructions (Told Nicotine versus Told Placebo) and nicotine (Received Nicotine versus Received Placebo). The balanced placebo design offers a powerful methodology for studying many aspects of smoking behaviour and nicotine effects, and three examples are given to illustrate its potential in this field: nicotine titration, nicotine and performance, and priming effects in smoking relapse. PMID- 1859937 TI - The focus and conduct of clinical trials. AB - This paper discusses some issues regarding how putative stop-smoking treatments should be evaluated. Preliminary evaluations of treatments have used withdrawal symptoms as a surrogate for abstinence in an attempt to decide those treatments on which to carry out expensive full-scale clinical trials. However, withdrawal symptom severity has not been shown to relate to long-term abstinence in any prospective studies. Until a better understanding of the relationship between withdrawal symptoms and abstinence is obtained withdrawal symptoms cannot be considered an appropriate surrogate for abstinence. Research is needed into what pattern of short-term abstinence provides the best predictor of long-term abstinence. Evidence from carbon monoxide validation of short-term abstinence raises doubts about whether minor lapses back to smoking are likely to lead to full blown relapse. Further research into the use of expired-air CO in validation of claims of abstinence is required. Finally, the traditional clinical trials format is not well suited to evaluation of treatment programmes with a large behavioural component. An alternative based on the principles underlying biological evolution is proposed. PMID- 1859938 TI - Immunology of the lung in HIV infection: the pathophysiologic basis for the development of tuberculosis in the AIDS setting. AB - Active tuberculosis is now recognized as a frequent and serious complication of infection with the human immunodeficiency virus (HIV), the causative agent of AIDS. HIV mediated alteration in host defenses against mycobacteria contribute to the magnitude and severity of this problem. HIV can affect a variety of cellular mechanisms important in the restriction of mycobacterial growth. Qualitative and quantitative defects in T lymphocyte function result from direct HIV infection of cells expressing the CD4 epitope, and can severely limit the production of macrophage activating cytokines capable of inducing an anti-mycobacterial state in cells of monocyte lineage. In addition, macrophages themselves are susceptible to HIV infection, and have been shown to be defective with respect to a variety of host defense functions. Both T4 lymphopenia and HIV infected macrophages are present in the lower respiratory tract of HIV infected individuals, a circumstance which likely underlies the unique susceptibility of HIV infected to tuberculosis. PMID- 1859940 TI - The impact of HIV infection on the global epidemiology of tuberculosis. AB - HIV is the strongest risk factor for tuberculous disease observed in the last 100 years in subjects infected with tubercle bacilli. Its impact upon tuberculosis incidence is so great that it has disrupted the balance between the tubercle bacillus and the community. The breakdown rate from tuberculous infection to active tuberculosis in persons infected dually is at least 30%. Although adequate chemoprophylaxis would prevent a considerable number of tuberculosis cases among these individuals, its application is not feasible in developing countries with a high prevalence of both tuberculous and HIV infections. Thus it seems that very little can be done against the increase in the incidence of tuberculosis caused by HIV. The only feasible measure to contain the transmission of tuberculous infection is to achieve a high cure rate and a high detection rate of smear positive and other cases. This would enable us to contain-to an extent-the transmission of tuberculous infection. The results of IUATLD assisted National Tuberculosis Programmes in Tanzania and Malawi show that this can be achieved. PMID- 1859939 TI - Tuberculosis and human immunodeficiency virus infection during the 1990's. AB - Among the many infectious complications of infection with human immunodeficiency virus (HIV), tuberculosis is now recognized as one of the most important. Coexisting HIV infection is believed responsible for the soaring incidence of tuberculosis in Africa, and for the increase in the number of reported cases in the United States. As HIV-induced immunosuppression worsens, tuberculosis may supervene by reactivation of remotely acquired infection or failure to defend against newly acquired Mycobacterium tuberculosis. Both mechanisms undoubtedly occur in Africa where the rate of exposure is high; the former prevails in the United States. The risk of tuberculous infection progressing to tuberculous disease is about six times higher in HIV seropositive than seronegative persons. Although not incontrovertibly established, tuberculosis probably also has a deleterious effect on coexisting HIV infection, either by accelerating the rate of destruction of CD4+ lymphocytes and/or promoting the release of new virions from HIV-infected macrophages. Tuberculosis, whether HIV-linked or not, can be controlled by the traditional means of case-finding and treatment, vaccination with BCG, and chemoprophylaxis. HIV infection can be controlled by eliminating high-risk behavior, and using uncontaminated blood and other medical supplies. An extensive campaign is needed to prevent further spread of these dual scourges that are overwhelming already meager health resources in many parts of the world. PMID- 1859942 TI - A transitional phase. PMID- 1859941 TI - Government intervention programs in HIV/tuberculous infection. Outline of guidelines for national tuberculosis control programs in view of the HIV epidemic. AB - Tuberculosis is one of the most widespread infections known in the world. WHO estimates that in 1990, 1.7 billion people, or one third of the world population, are or have been infected with the tubercle bacillus. Fortunately, few of those infected develop active forms of the disease but it is estimated that in 1990, there will be 8 million new cases and 2.9 million deaths from tuberculosis in the world. This already alarming situation of the tuberculosis problem is getting worse, mainly due to the AIDS epidemic. A basic understanding of tuberculosis/HIV epidemiology is necessary and priority actions are to be strongly recommended for application in government intervention programs. They are specified in the present article. PMID- 1859943 TI - The annual tuberculosis infection rate, the tuberculin survey and the tuberculin test. AB - In the present stage of development where tuberculosis mortality has lost its statistical significance because of effective chemotherapy, it is generally recognized that the most reliable measure of the extent of the tuberculosis problem in a population is the "annual tuberculosis infection rate" or incidence of infection. In countries where infection with the bovine type of tubercle bacilli no longer exists, as is the case in the majority of low prevalence countries, the annual infection rate expresses that proportion of the population under study which will be primarily infected, or reinfected with tubercle bacilli from a human source in the course of one year. The annual tuberculosis infection rate is also the best measure for following the trend of the tuberculosis problem in a given population and for evaluating the total effects of organized efforts to control tuberculosis. PMID- 1859944 TI - Evaluation of the BCG revaccination programme of schoolchildren in Finland. AB - OBJECTIVE: To evaluate the need for the BCG revaccination programme of schoolchildren in Finland. DESIGN: Investigating tuberculin sensitivity using the standard WHO Mantoux test and developing a model to estimate the risk of discontinuation, assuming that the annual incidence of tuberculosis within ten years after revaccination will remain at its present level; that the revaccination rate will be 2, 6 or 20%; and that the degree of protection will be 10, 20, 40 or 80%. SETTING AND PARTICIPANTS: Urban and rural schoolchildren- 3,346 vaccinated with Copenhagen and 655 with Glaxo BCG vaccine at birth. RESULTS OF DATA ANALYSIS: The annual incidence of tuberculosis was 4.2 per 100,000 in the age-group 15-24 years. BCG revaccination was given formerly to 20% of the age cohort but nowadays only 6% or 2% meet the criteria after receiving either Copenhagen or Glaxo BCG at birth. After discontinuation the expected increase of tuberculosis in the age-group 15-24 years is predicted to fall within the limits of 0.1-24 cases per year. If 2% are left without revaccination the increase will be 0.1-2.4 cases. CONCLUSIONS: Due to the low annual incidence of tuberculosis in adolescents and to the small risk of increase the BCG revaccination programme has been discontinued from 1990 onwards. PMID- 1859945 TI - Tuberculosis in children. Guidelines for diagnosis, prevention and treatment (a statement of the Scientific Committees of the IUATLD). PMID- 1859946 TI - T cell response in acquired protective immunity to Mycobacterium tuberculosis infection. PMID- 1859947 TI - The mysterious "urethral syndrome". PMID- 1859948 TI - Sex hormones, autoimmune diseases, and immune responses. PMID- 1859949 TI - Risk of neoplasia and malignancy in "dominant" thyroid swellings. AB - OBJECTIVE: To determine the risk of neoplasia and malignancy in "dominant" thyroid swellings. DESIGN: Prospective analysis during six years. SETTING: Thyroid clinic serving the Grampian region. PATIENTS: 574 consecutive patients presenting with a discrete thyroid swelling, of whom 179 (31%) were classified clinically as having a dominant area of enlargement within a multinodular gland. RESULTS: After clinical and cytological assessment 77 dominant swellings were excised. Of the excised swellings, 45 were non-neoplastic and 32 neoplastic, including 11 malignant lesions. The minimum incidence of neoplasia and malignancy in all 179 dominant swellings was therefore 18% and 6% respectively. CONCLUSION: Dominant thyroid swellings should be regarded with greater clinical suspicion than has been traditional. PMID- 1859950 TI - Reported social alcohol consumption during pregnancy and infants' development at 18 months. AB - OBJECTIVE: To determine the relation between mothers' self reported drinking habits before, during, and after pregnancy and infants' mental and motor development at 18 months of age. DESIGN: Follow up study of all singleton live births born to primigravidas living in Dundee and booked into antenatal clinics from 1 May 1985 to 30 April 1986. SETTING: District of Dundee. SUBJECTS: 846 children aged 18 months, of whom 592 attended for assessment. MAIN OUTCOME MEASURES: Scores on Bayley scales of infant mental and motor development. RESULTS: For full term children, maternal alcohol consumption was not significantly related to any adverse effect on the children's mental or motor development measures at age 18 months. After confounding factors had been controlled for, alcohol consumption before pregnancy and after pregnancy was significantly related to better motor performance and mental performance. CONCLUSION: Pregnant women probably need not abstain from alcohol altogether as no detectable adverse relation was found between the child's mental and physical development and the mother's weekly consumption at levels in excess of 100g absolute alcohol. However, to allow for a margin of safety and taking into account the findings of an earlier phase of this study on the immediate effects on the newborn, it is recommended that pregnant women should drink no more than eight units of alcohol a week, the equivalent of about one drink a day. PMID- 1859951 TI - What makes insulin injections painful? PMID- 1859952 TI - Cost of road traffic accidents to an orthopaedic department. PMID- 1859953 TI - Multilevel assessment of immunisation uptake as a performance measure in general practice. AB - OBJECTIVE: To provide a measure of general practitioners' performance regarding uptake of immunisation against pertussis, taking account of the impact of patient characteristics on levels of uptake. DESIGN: Multilevel model of immunisation status against six measures of patient characteristics (level 1 predictor variables) with practice constraints as level 2 variables. SETTING: 126 practices in southern England. SUBJECTS: 2048 infants identified from infant surveillance and immunisation records. MAIN OUTCOME MEASURES: Top 10 practices with respect to uptake of pertussis immunisation according to a "null" model (model A) and according to a model that included six level 1 variables (model B); differences in ranking between the two models. RESULTS: Practices with low numbers of infants' requiring immunisation had imprecise and unstable uptake rates (range 0% 100%). With the multilevel procedure, after controlling for patient characteristics, practices in suburban catchment areas comprised largely of mature or young professionals performed best. Most improved performances when patient characteristics were taken into account were in practices in areas with a stable population and local authority housing--one such practice improved its ranking by 47 places. CONCLUSIONS: Crude uptake rates are inadequate performance indicators. Alternative approaches suggest that praiseworthy efforts to raise immunisation rates in unpromising areas are unrewarded by simple target based assessments. PMID- 1859954 TI - Adenoma screening and colorectal cancer. PMID- 1859955 TI - Audit and standards in new general practice. PMID- 1859957 TI - Forensic use of DNA tests. PMID- 1859956 TI - Magnetic resonance imaging--1: Basic principles of image production. PMID- 1859958 TI - Undergraduate medical education: present state and future needs. PMID- 1859959 TI - ABC of antenatal care. Preterm labour. PMID- 1859960 TI - Psychological therapy in the NHS. PMID- 1859961 TI - Assessing protective effect of sunscreen products. PMID- 1859962 TI - Disciplinary procedures and secrecy. PMID- 1859963 TI - Freedom of speech in the new NHS. PMID- 1859964 TI - Deaths certified as due to coronary artery disease. PMID- 1859965 TI - Golf related head injuries in children. PMID- 1859966 TI - Diastasis of the pubic symphysis in pregnancy. PMID- 1859967 TI - Immunoreactive trypsinogen concentrations in infants with meconium ileus. PMID- 1859968 TI - Sodium valproate in pregnancy. PMID- 1859969 TI - Rapid one step urine tests in early pregnancy. PMID- 1859970 TI - Altitude treatment for whooping cough. PMID- 1859972 TI - Breast cancer screening: the current position. PMID- 1859971 TI - Talc granulomas. PMID- 1859974 TI - General practitioner outpatient referrals. PMID- 1859973 TI - Nightmare of extracontractual referral. PMID- 1859976 TI - Liaison between child psychiatrists and social services staff. PMID- 1859975 TI - General practitioners' attendance at case conferences. PMID- 1859977 TI - Part time training in obstetrics and gynaecology. PMID- 1859978 TI - Surveys of patient satisfaction. PMID- 1859979 TI - Duties of juniors and consultants. PMID- 1859980 TI - Junior doctors, nurses and drips. PMID- 1859981 TI - Research posts for general practitioners. PMID- 1859982 TI - Scandal threatens French blood transfusion service. PMID- 1859983 TI - When medical audit starts to count. PMID- 1859984 TI - Magnetic resonance imaging--2: Clinical uses. PMID- 1859986 TI - ABC of antenatal care. Multiple pregnancy. PMID- 1859985 TI - Ethics, commerce, and kidneys. PMID- 1859988 TI - Zidovudine after occupational exposure to HIV. PMID- 1859987 TI - Drugs, HIV, and prisons. PMID- 1859989 TI - Domiciliary thrombolytic treatment. PMID- 1859990 TI - Routine testing for HIV at infertility clinics. PMID- 1859991 TI - Thalassaemia in pregnancy. PMID- 1859992 TI - Recording diastolic blood pressure in pregnancy. PMID- 1859993 TI - Persistent vegetative state. PMID- 1859994 TI - Surgeons who undertake surgery for colorectal cancer. PMID- 1859995 TI - General practitioners' access to x ray services. PMID- 1859996 TI - Intra-articular injections in capsulitis. PMID- 1859997 TI - General practitioners' attendance at child protection case conferences. PMID- 1859998 TI - How to produce a service specification. PMID- 1859999 TI - Benefits of changes in the NHS. PMID- 1860000 TI - Homeless people and psychiatric care. PMID- 1860001 TI - Coronary heart disease and elderly people. PMID- 1860002 TI - New deal for old hearts. PMID- 1860003 TI - Where should we train doctors in the future? PMID- 1860004 TI - Managing violence in psychiatric hospitals. PMID- 1860006 TI - The BMA in agony. PMID- 1860005 TI - The familial transmission of alcoholism. PMID- 1860007 TI - AMA rejects compulsory HIV testing. PMID- 1860009 TI - Does plasma cholesterol concentration predict mortality from coronary heart disease in elderly people? 18 year follow up in Whitehall study. AB - OBJECTIVE: To explore the extent to which the relation between plasma cholesterol concentration and risk of death from coronary heart disease in men persists into old age. DESIGN: 18 year follow up of male Whitehall civil servants. Plasma cholesterol concentrations and other risk factors were determined at first examination in 1967-9 when they were aged 40-69. Death of men up to 31 January 1987 was recorded. SUBJECTS: 18,296 male civil servants, 4155 of whom died during follow up. MAIN OUTCOME MEASURES: Cause and age of death. Cholesterol concentration in 1967-9 and number of years elapsed between testing and death. RESULTS: 1676 men died of coronary heart disease. The mean cholesterol concentration in these men was 0.32 mmol/l higher than that in all other men (95% confidence interval 0.26 to 0.37 mmol/l). This difference in cholesterol concentrations fell 0.15 mmol/l with every 10 years' increase in age at screening. The risk of raised cholesterol concentration fell with age at death. Compared with other men cholesterol concentration in those who died of coronary heart disease was 0.44 mmol/l higher in those who died aged less than 60 and 0.26 mmol/l higher in those aged 60-79 (p = 0.03). For a given age at death the longer the gap between cholesterol measurement and death the more predictive the cholesterol concentration, both for coronary heart disease and all cause mortality (trend test p = 0.06 and 0.03 respectively). CONCLUSION: Reducing plasma cholesterol concentrations in middle age may influence the risk of death from coronary heart disease in old age. PMID- 1860010 TI - Computerisation of primary care in Wales. AB - OBJECTIVE: To obtain information about the computerisation of general practice in Wales, and to enable more effective planning of educational provision for doctors and other primary health care workers. DESIGN: Postal questionnaire sent to all general practices in Wales. SUBJECTS: 553 general practices, of which 401 (73% replied). RESULTS: The level of computerisation varied from 11 (85%) of practices in Powys Family Health Services Authority to 22 (40%) in Mid Glamorgan. Less than half of practices had a computer in only two authorities. The commonest uses of the computer were for patient registration (208 practices), repeat prescribing (180), call and recall of patients (165), and partial clinical records (122). The main suppliers were VAMP (78 practices), AAH Meditel (46), and AMC (23). 102 of 226 practices with a computer had a terminal on each doctor's desk. Just 33 practices had full patient notes on computer and 51 had modems for electronic communication. CONCLUSION: Mechanisms to encourage greater and more sophisticated use of computers and information technology need to be explored. PMID- 1860008 TI - Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria. AB - OBJECTIVE: To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy (albuminuria greater than 300 mg/24h). DESIGN: Open randomised controlled study of four years' duration. SETTING: Outpatient diabetic clinic in tertiary referral centre. PATIENTS: 44 normotensive (mean blood pressure 127/78 (SD 12/10) mm Hg) insulin dependent diabetic patients with persistent microalbuminuria (30-300 mg/24h). INTERVENTIONS: The treatment group (n = 21) was initially given captopril (25 mg/24 h). The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months. The remaining 23 patients were left untreated. MAIN OUTCOME MEASURES: Albuminuria, kidney function, development of diabetic nephropathy (albuminuria greater than 300 mg/24 h), and arterial blood pressure. RESULTS: Clinical and laboratory variables were comparable at baseline. Urinary excretion of albumin was gradually reduced from 82 (66-106) to 57 (39-85) mg/24 h (geometric mean (95% confidence interval)) in the captopril treated group, whereas an increase from 105(77-153) to 166 (83-323) mg/24 h occurred in the control group (p less than 0.05). Seven of the untreated patients progressed to diabetic nephropathy, whereas none of the captopril treated patients developed clinical overt diabetic nephropathy (p less than 0.05). Systemic blood pressure, glomerular filtration rate, haemoglobin A1c concentration, and urinary excretion of sodium and urea remained practically unchanged in the two groups. CONCLUSIONS: The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria. PMID- 1860011 TI - Consultants' involvement in the contracting process in Yorkshire region. PMID- 1860012 TI - Raised proinsulin concentration as early indicator of beta cell dysfunction. PMID- 1860013 TI - Molecular genetics of the major psychoses: the role of the Medical Research Council. PMID- 1860014 TI - Collaborative strategies in the molecular genetics of the major psychoses. PMID- 1860015 TI - The search for the psychosis gene. PMID- 1860017 TI - Evidence for a pseudo-autosomal locus for schizophrenia using the method of affected sibling pairs. AB - A susceptibility locus for schizophrenia in the 'pseudo-autosomal' region has been proposed on the basis of the reported excess of sex-chromosome aneuploidies (e.g. XXY and XXX) among patients with schizophrenia and the finding that schizophrenic sib-pairs are more often of the same than of the opposite sex. This hypothesis has been tested in 83 sibships with two or more siblings fulfilling Research Diagnostic Criteria for schizophrenia or schizoaffective disorder. Alleles at the pseudo-autosomal telomeric locus DXYS14, which is unlinked with sex, were analysed using the method of affected sib-pairs. Affected sibs shared alleles at DXYS14 more frequently than expected by random Mendelian assortment, supporting genetic linkage between DXYS14 and schizophrenia. PMID- 1860016 TI - The genetics of schizophrenia is the genetics of neurodevelopment. PMID- 1860018 TI - Changes in patient coping style following individual and family treatment for schizophrenia. AB - Changes in relatives' affective attitudes are important contributors to the impact of family psychoeducational programmes on the course of schizophrenia. It remains unclear whether similar changes occur in the interactional style of schizophrenic patients participating in psychoeducational treatment. This study examined changes in the interactional style (coping style) of 33 schizophrenic patients in individual or family treatment. Significant changes were seen in the interactional style of the patients participating in the individual treatment. Similar changes were evident, but not significant, in the family treatment group. The quality of patient interactional style before or after treatment did not predict relapse in either group. Changes in relatives' interactional style early in family treatment are necessary to affect the short-term course of schizophrenia. Modification in patient behaviour during the early phase does not have similar predictive value. PMID- 1860019 TI - Negative modes of relating, marital quality and depression. AB - Young married couples, with or without a depressed wife, were divided into three groups according to marital quality. Negative modes of relating were assessed by self-rating and partner-rating questionnaires. The intercorrelation of scores for different modes of relating was higher on partner-rating than on self-rating scales. There was a significant gradient of mean negative-relating scores across the three levels of marital quality. The partner-ratings of depressives and their husbands were higher on all negative-relating scales than those of non-depressed women and their husbands. The self-ratings of the depressives corresponded with these negative ratings while those of their husbands did not. The partner-rating scores differentiated between the depressives with poor marriages and those with better marriages. PMID- 1860021 TI - Social influences on the course of anxious and depressive disorders in school-age children. AB - In a follow-up study of 49 children and adolescents with anxious or depressive disorders up to 50% had not recovered. In the 12 months preceding onset there were no social factors which predicted recovery at follow-up. Between onset and follow-up the children were less likely to be exposed to undesirable life events, and significant improvements in maternal confiding relationships were reported. Neither of these improvements predicted the level of recovery at follow-up. Poor recovery is best predicted by moderate to poor friendships after the onset of disorder, particularly for those with a diagnosis of depression. Further confirmation is provided that direct interviewing of children by trained personnel using semistructured schedules is a valid method for determining mental symptoms and perception of recent friendships. PMID- 1860020 TI - Plasma levels of fluphenazine in patients receiving fluphenazine decanoate. Relationship to clinical response. AB - The levels of fluphenazine and fluphenazine sulphoxide in schizophrenic patients who were randomly assigned to receive either 5 mg or 25 mg of fluphenazine decanoate every two weeks were monitored. Patients treated with 25 mg of fluphenazine decanoate required three months to reach a steady-state plasma level, indicating that those patients who are being converted from oral to depot fluphenazine should continue to receive oral supplementation during the first three months of treatment with fluphenazine decanoate. Plasma levels of fluphenazine sulphoxide were lower than levels of fluphenazine. At six and nine months following randomisation, there was a statistically significant relationship between lower fluphenazine plasma levels and an increased risk of psychotic exacerbations. A relatively weak relationship was found between fluphenazine plasma levels and akinesia, but non-significant relationships between fluphenazine levels and other neurological side-effects including akathisia, retardation, and tardive dyskinesia. Monitoring the plasma levels may be helpful to clinicians who are attempting to treat stabilised patients with the lowest effective dose of fluphenazine decanoate. PMID- 1860022 TI - Care of chronic neurotic out-patients by community psychiatric nurses. A long term follow-up study. AB - Ninety-nine neurotic patients from a controlled trial of CPN v. psychiatric out patient aftercare were followed up seven years later. Of the 92 survivors, 76 were successfully interviewed. Few differences were found between the groups. Chronic mild symptoms and moderate social disability persisted, and tended to worsen a little. Treatment patterns persisted for one to two years beyond the original study; the CPN group had more CPN contacts, fewer psychiatric out patient contacts and less psychiatric care. Thereafter, more out-patients were discharged from psychiatric care and care patterns for the two groups became similar. Out-patients attended more non-psychiatric out-patient clinics than the CPN group, but it is possible that this reflected pre-existing differences. About a third of patients remained in contact with the psychiatric service during follow-up. PMID- 1860023 TI - A comparison of the withdrawal responses of heroin and methadone addicts during detoxification. AB - This study compares the withdrawal responses of methadone and heroin addicts during a ten-day in-patient detoxification programme with methadone. Contrary to suggestions in the literature, the methadone group reported more severe withdrawal symptoms during both the acute withdrawal phase and the recovery phase. There were no differences between the two groups in onset or duration of symptoms. Whereas there may be reasons to favour methadone as a maintenance drug, its use may lead to difficulties during withdrawal. PMID- 1860024 TI - Is sex necessarily a risk factor to depression? AB - "To isolate and quantify possible determinants of any increased prevalence of depressive disorders in women we studied a select group of men and women, initially similar in terms of a number of putative social determinants of depression, and reviewed the sample five years later when social role diversity was anticipated. We used the Diagnostic Interview Schedule (DIS) to generate DSM III and RDC diagnoses to estimate lifetime depressive disorders, and established (via corroborative reports) the likely accuracy of those data. Despite lifetime depression being a relatively common experience, no significant sex differences in depressive episodes were demonstrated, suggesting the possible irrelevance of biological factors in determining any sex difference. As there was not major social role divergence over the five year study, we interpret the lack of a sex difference as a consequence, and suggest that findings support the view that social factors are of key relevance in determining any female preponderance in depression described in general population studies." PMID- 1860025 TI - First episode schizophrenia: predicting outcome. PMID- 1860026 TI - Gender-identity clinic patients. PMID- 1860027 TI - Musical and verbal hallucinations. PMID- 1860028 TI - Failure to convulse with ECT. PMID- 1860029 TI - Anorexia nervosa in the elderly. PMID- 1860030 TI - Family intervention. PMID- 1860031 TI - Uraemia and mania. PMID- 1860032 TI - The social networks of long-term patients. PMID- 1860033 TI - Incestuous abuse in psychiatric patients. PMID- 1860034 TI - Tolbutamide and fatal water intoxication. PMID- 1860035 TI - Tardive oculogyric crisis and obsessional thoughts. PMID- 1860036 TI - Drug-induced koro in a non-Chinese man. PMID- 1860037 TI - Dorsal accessory inferior olive activity diminishes during acquisition of the rabbit classically conditioned eyelid response. AB - Eight rabbits were implanted with chronic recording electrodes in the rostromedial region of the dorsal accessory inferior olive (DAO). Multiple-unit DAO activity was recorded during 5 training sessions consisting of paired tone conditioned stimulus (CS) and air puff unconditioned stimulus (US) trials. Initially, the air puff US produced a large somatosensory-evoked response in the DAO during the paired CS-US presentations. As percent CRs increased across sessions, however, the DAO activity on paired trials decreased dramatically. In contrast, there were no significant decreases in DAO activity on US-alone trials presented at the end of each paired conditioning session. These results suggest that an associative process suppresses DAO activity during classical eyelid conditioning. Possible mechanisms of DAO inhibition and its involvement as part of the US 'reinforcement' pathway are discussed. PMID- 1860038 TI - The effects of total and partial callosal agenesis on the development of paw preference performance in the BALB/cCF mouse. AB - The relation between callosal defects and paw preference was investigated in 85 male mice of the BALB/cCF strain. Paw preference was also studied in 30 male Swiss mice. Directional laterality and magnitude of laterality devoid of directionality were evaluated independently. The study of the magnitude of paw preference showed that male BALB/cCF mice were more strongly lateralized than Swiss mice. There was no difference between BALB/cCF mice with callosal defects (abnormal group) and normal BALB/cCF mice. The analysis of directional laterality indicated a population tendency for left-paw use in BALB/cCF as compared to Swiss mice. Furthermore, the percentage of left-pawed animals in the abnormal group (78%) was significantly different from chance level, as opposed to an absence of such differences in the normal BALB/cCF and in Swiss mice. It was concluded that developmental disturbance of the corpus callosum is related to the appearance of a directional populational asymmetry in paw preference. PMID- 1860039 TI - Long-lasting change in the membrane-associated protein kinase C activity in the hippocampal kindled rat. AB - The effect of hippocampal kindling on protein kinase C (PKC) activity and protein concentration was investigated in rat amygdala/pyriform cortex (AM/PC) and right (contralateral) and left (ipsilateral) hippocampus (HIPP). There was no difference in cytosolic PKC activity between control and kindled groups in any part of the brain. The membrane-associated PKC activity was altered as follows. One week after the last seizure, it was significantly increased in both right (by 26%, P less than 0.05) and left HIPP (by 30%, P less than 0.02). Four weeks after the last seizure, it was significantly increased in the AM/PC (by 14%, P less than 0.02), right HIPP (by 37%, P less than 0.01) and left HIPP (by 24%, P less than 0.05). The protein concentrations in the crude cytosolic extracts prior to elution of PKC through DE-52 columns were significantly increased in the AM/PC (by 11%, P less than 0.05) and right HIPP (by 18%, P less than 0.02) 4 weeks after the last seizure. In the membrane extracts, there was a significant increase by 23% (P less than 0.02) in the left HIPP 1 week after the last seizure. In the fraction co-eluted with PKC, a significant increase in protein concentration of the cytosolic preparation was confirmed in the AM/PC (by 12%, P less than 0.05) as well as in the left HIPP (by 15%, P less than 0.05) 4 and 1 weeks respectively after the last seizure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860040 TI - Monoclonal antibodies identify two novel proteins associated with vasopressin secretory granules of the rat neurohypophysis. AB - Immunocytochemical and immunoblotting technique have been used to characterize the antigens recognized by two monoclonal antibodies (MAbs C6 and D5) produced against dissociated cells from punches of neonatal supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei of the rat. Peroxidase immunocytochemistry revealed that both MAbs label magnocellular perikarya in the adult and neonatal SON and PVN as well as smaller neurons in the suprachiasmatic nucleus. Axons of the hypothalamo-neurohypophysial tract are also immunolabeled within the hypothalamus and zona interna of the median eminence, and C6 and D5 each bind specifically to both the adult and neonatal neurohypophysis. Dual-label immunofluorescence experiments employing C6 or D5 simultaneously with rabbit antisera specific for either oxytocin, neurophysin or vasopressin neurophysin revealed that C6 binds only to vasopressinergic magnocellular perikarya in the SON, while D5 labels both vasopressinergic and a small subset of oxytocinergic magnocellular neurons. Post-embedding immunogold analysis of MAb binding to the neurohypophysis at the ultrastructural level showed that both C6 and D5 recognize antigens associated with large dense core neurosecretory granules in a subset of neurosecretory axons. Initial biochemical characterization of the antigens recognized by C6 and D5 was performed using SDS-PAGE and Western immunoblotting. MAbs C6 and D5 label single protein bands with apparent molecular weights of 38 and 68 kDa, resp., in blots of reduced extracts from the adult neurointermediate lobe. No cross-reactivity between C6 and D5 and the neurophysins was apparent, nor did anti-neurophysin sera recognize the bands identified by C6 and D5. We have therefore designated these novel antigens as VPGP38 and VPGP68 for VasoPressin Granule Proteins. PMID- 1860041 TI - Ontogeny of the electrophysiological activity of dopaminergic cells with special reference to the influence of adrenal medullary grafts on aging. AB - A variety of neurological impairments during aging involves pathological changes in the basal ganglia, with the consequent deterioration of motor activities. The purpose of this study was to determine whether the extracellular activity of dopaminergic cells of the substantia nigra pars compacta of Wistar rats changes with age, and if so whether ventricular adrenal medullary grafts can influence the electrophysiological activity of the oldest age group. The results indicate that there is a significant decrease in the firing frequency of substantia nigra cells which begins at 18 months of age and is most prominent by 22-24 months of age. The rate of firing was improved with adrenal medulla grafts placed in the lateral ventricle. In addition, it was also observed that with age there is an increase in the number of cells which fire at slower frequencies. Quinpirole administration induced a significant decrease in firing frequency in all age groups, including the grafted animals. These results suggest that in the aged Wistar rats there is an impairment in the response of SNC cells, which can be partially restored by fetal adrenal medullary grafts. PMID- 1860042 TI - Periaqueductal gray stimulation produces a spinally mediated, opioid antinociception for the inflamed hindpaw of the rat. AB - The objective of the present study was to characterize stimulation-produced antinociception from the periaqueductal gray matter (PAG) in rats with unilateral hindlimb inflammation induced by an intraplantar injection of Freund's complete adjuvant. Rats were chronically implanted with a bipolar stimulating electrode in the PAG. Nociception was assessed using a paw pressure test. Prior to inflammation, PAG stimulation significantly increased paw pressure threshold in both paws compared to non-stimulated controls. Following inflammation, PAG stimulation inhibited nociception in the inflamed, but not the non-inflamed paw. Systemic administration of naloxone blocked antinociception from ventral, but not dorsal PAG stimulation sites. Intrathecal, but not subcutaneous, administration of quaternary naltrexone completely blocked stimulation-produced antinociception from the PAG. The known increased levels of endogenous opioids occurring in the spinal cord ipsilateral to the site of inflammation suggest a mechanism for the selective antinociceptive effect of ventral PAG stimulation seen for the inflamed paw. PMID- 1860043 TI - Focal cerebral ischemia in chronic hypertension: no protection by (R) phenylisopropyladenosine. AB - The effects of the adenosine agonist, (R)-phenylisopropyladenosine on focal cerebral ischemia induced by middle cerebral artery occlusion were investigated in spontaneously hypertensive rats. The drug was given 30 min before occlusion and each hour thereafter for 6 h. The neurological status of the rats was estimated 2, 24 and 48 h after occlusion. Infarct volumes were measured 48 h after occlusion (Cresyl violet-stained sections). (R)-Phenylisopropyladenosine did not significantly reduce infarct size, nor did it modify the neurological score. As there is considerable evidence of the neuroprotective effects of adenosine in normotensive rats, the present results may be due to a more abrupt reduction in cerebral blood flow in the territory surrounding the ischemic core, where neuroprotection could be expected, in the spontaneously hypertensive rat strain. Consequently, neuroprotection may be more difficult when focal cerebral ischemia is associated with hypertension. PMID- 1860044 TI - The relationship of hand preference to anatomy of the corpus callosum in men. AB - Area of the midsagittal section of the corpus callosum, particularly in the region of the isthmus, was found previously to be greater in non-consistent-right handed than consistent-right-handed men in a sample of 15 postmortem cases. Seven cases were obtained subsequent to this analysis. The new cases showed the same association previously observed between hand preference and area of the corpus callosum and its isthmus. In addition, a high negative correlation was found between isthmal area and a quantitative score of the direction and magnitude of hand preference. In the new cases, handedness was predicted better than chance using statistical functions of callosal anatomy derived from the previous group of 15 cases. These results support a relationship between variation in callosal anatomy and handedness in men and the hypothesis of a relationship between callosal morphology and functional asymmetry. The lack of such a relationship among women suggests that the developmental mechanisms leading to callosal anatomical variation in relation to lateralization are influenced by sex hormones. Methodological issues in the use of magnetic resonance imaging for the quantitative study of callosal anatomy are discussed. PMID- 1860045 TI - The nigrostriatal dopaminergic system in MPTP-treated mice shows more prominent recovery by syngeneic adrenal medullary graft than by allogeneic or xenogeneic graft. AB - Following systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), young (2-month-old) C57BL/6 mice show decreased dopaminergic (DA) nigrostriatal fibers and DA concentration in the striatum. We transplanted syngeneic, allogeneic and xenogeneic adrenal medullary grafts into the striatum of the MPTP-treated young mice and compared the survivability of grafted chromaffin cells and the recovery of intrinsic host DA fibers using computerized image analysis of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers and high performance liquid chromatography with electrochemical detection (LCEC). The grafted syngeneic adrenal chromaffin cells survived better than allogeneic or xenogeneic chromaffin cells, and host DA nigrostriatal fiber recovery was more prominent in mice with a syngeneic graft than in mice with an allogeneic or xenogeneic graft. However, the degree of host fiber recovery in mice with allogeneic or xenogeneic mice was greater than in mice with a sham operation alone, even though the allografts and xenografts had no surviving chromaffin cells. Allografts and xenografts showed prominent rejection responses, with T lymphocyte infiltration in addition to macrophages. We conclude that a syngeneic adrenal graft survives better than an adrenal allograft or xenograft and promotes recovery of the intrinsic host nigrostriatal DA fibers. We also conclude that grafted chromaffin cell survivability influences the degree of host DA fiber recovery following MPTP depletion. Adrenal medullary grafts to Parkinsonian patients are currently under way in a large number of hospitals; we suggest that greater attention be paid to methods which lead to enhanced survival of the grafted chromaffin cells, since survivability might be closely related to the functional recovery of these patients. PMID- 1860047 TI - Effects of nicotine withdrawal on the local cerebral glucose utilization in conscious rats. AB - Chronic infusion of nicotine has been shown to result (1) in an increase in nicotine binding sites in the brain and (2) in a distinct pattern of increases in local cerebral metabolic rate for glucose (CMRglc). The present study addresses two questions: (1) whether a one-day withdrawal of nicotine after a two-week exposure is long enough to restore local CMRglc to the preinfusion values and (2) whether an acute nicotine infusion after one day's withdrawal would influence local CMRglc. Chronic infusion of L-nicotine (12.5 micrograms/kg/min) was performed by osmotic minipumps. Local CMRglc was measured using the quantitative 2-deoxyglucose method in conscious rats. The following results were obtained: (1) a one-day withdrawal of nicotine after a two-week chronic infusion restores local CMRglc to a pattern which is close to the control pattern obtained without any nicotine infusion, and (2) an acute infusion of nicotine after a one-day withdrawal of a chronic nicotine infusion induces distinct increases in local CMRglc of several brain structures; these are essentially identical with structures which are activated during an acute nicotine infusion in otherwise untreated rats (no chronic infusion). The data indicate: (1) The main effects of chronic nicotine infusion on local CMRglc have disappeared after one day of nicotine withdrawal. (2) An acute load of nicotine in such nicotine-withdrawal rats has effects on local CMRglc which resemble those found in previously untreated rats during an acute nicotine infusion. (3) In contrast to most binding studies which have shown persisting increases in nicotine binding sites after one day's withdrawal of chronic nicotine, local CMRglc is restored to control values and can be again activated by an acute nicotine infusion. PMID- 1860046 TI - The effects of short periods of immobilization on the hamster circadian clock. AB - Recent findings indicate that stimuli which induce an acute increase in locomotor activity can induce phase shifts in the circadian clock of hamsters. Support for the actual role of the acute increase in activity in the mediation of these phase shifts is provided by the observation that immobilization can totally block phase shifts in the activity rhythm that are normally induced in response to exposure to two of these stimuli, either a pulse of darkness or an injection of a benzodiazepine. In order to further examine the effects of immobilization on the circadian system of hamsters, 3 studies were carried out. In a first study, the effects of a 3-h period of immobilization procedure on the phase of the free running circadian rhythm of locomotor activity were tested at 8 different circadian times. Immobilization during the highly active part of the animal's activity cycle resulted in phase delays in the activity rhythm, while immobilization at other circadian times had little or no effect on the circadian time-keeping system. In two other studies, we reported that immobilization had no effect on phase shifts normally induced by 3-h pulses of light or injections of the protein synthesis inhibitor, cycloheximide, two stimuli that are clearly not associated with an increase in locomotor activity in hamsters. Thus, the ability of immobilization to block stimulus-induced phase shifts in the circadian clock appears to be specific to those stimuli that induce an acute increase in locomotor activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860048 TI - Distribution of synapses on fast and slow pyramidal tract neurons in the cat. An electron microscopic study. AB - Distributions of synapses on various portions of fast and slow pyramidal tract neurons (PTNs) in cat motor cortex were studied with electron microscopy. PTNs were identified by their antidromic invasion following stimulation of the medullary pyramid and were classified into fast and slow PTNs according to conduction velocities of their axons. Two fast and two slow PTNs were intracellularly labeled and, by systematic sampling, electron micrographs from various portions of these neurons were examined to compare the distributions of different types of synapses. It was found that most synapses formed on apical and basal dendrites of fast PTNs were with the dendritic shafts. In slow PTNs, while synapses on apical dendrites were mostly axospinous, about 70% of the sampled synapses on basal dendrites of slow PTNs were established with the dendritic shafts. Virtually all synapses on apical dendrites of slow PTNs belonged to asymmetrical type and most of the synapses sampled from basal dendrites of fast PTNs were also asymmetrical. On the other hand, about 29% of the synapses found on apical dendrites of fast PTNs were symmetrical and a trend was observed for this type of synapses to increase their number with increasing proximity to the cell body. Over 28% of the synapses on basal dendrites of slow PTNs were also symmetrical and seemed to be mainly distributed in layer VI. All synapses formed on the soma were symmetrical both for the fast and slow PTNs. PMID- 1860049 TI - Ionic mechanism of the outward current induced by extracellular ejection of interleukin-1 onto identified neurons of Aplysia. AB - The ionic mechanism of the effect of extracellularly ejected recombinant human interleukin-1-beta (rhIL-1) on the membrane of identified neurons R9 and R10 of Aplysia was investigated with voltage-clamp, micropressure-ejection, and ion substitution techniques. Micropressure-ejected rhIL-1 caused a marked hyperpolarization in the unclamped neuron. Clamping the same neuron at its resting potential level (-60 mV) and reejecting rhIL-1 with the same dose produced a slow outward current (I0(IL-1), 20-30 s in duration, 3-5 nA in amplitude) associated with a decrease in input membrane conductance. I0(IL-1) was decreased by depolarization and increased by hyperpolarization. The extrapolated reversal potential of I0(IL-1) was approximately +15 mV. I0(IL-1) was sensitive to changes in the external Na+ concentration but not to changes in K+, Ca2+ and Cl- concentrations, and was resistant to tetraethylammonium (5 mM) and 4 aminopyridine (5 mM). Neither perfusion of the neuron with 50 microM tetrodotoxin nor perfusion with 10 mM Co2+ seawater caused any changes in I0(IL-1). I0(IL-1) was partially reduced by 50 microM ouabain. These results suggest that extracellular IL-1 can induce a slow outward current associated with a decrease in Na+ conductance and the immunomodulator IL-1 can act directly on the nervous system as well as on the immune system. PMID- 1860050 TI - Major metabolites of (+/-)3,4-methylenedioxyamphetamine (MDA) do not mediate its toxic effects on brain serotonin neurons. AB - The two major metabolites of (+/-)3,4-methylenedioxyamphetamine (MDA), alpha methyldopamine (alpha-MeDA) and 3-O-methyl-alpha-methyldopamine (3-O-Me-alpha MeDA), were administered to rats intracerebroventricularly and into brain parenchyma. In addition, their precursors, (alpha-MeDOPA and 3-O-Me-alpha-MeDOPA, respectively) were administered systemically, individually and in combination. None of these treatments produced a lasting depletion of brain serotonin (5-HT). These findings suggest that neither of MDA's major metabolites mediate its toxic effects on 5-HT neurons and that either a minor metabolite is responsible or that alternate mechanisms are involved. PMID- 1860051 TI - Long-term enhancement of evoked potentials in raccoon somatosensory cortex following co-activation of the nucleus basalis of Meynert complex and cutaneous receptors. AB - Long-term enhancement of the evoked potential was induced in the primary somatosensory cortex of anaesthetized raccoons after mechanical stimulation of the skin was paired with electrical stimulation of the nucleus basalis of Meynert (NBM). Sets of 4 pulses, 0.5 ms duration at 300 Hz were delivered at 2-s intervals to the basal forebrain 80 ms before the glabrous skin on the 4th digit of the contralateral forepaw was stimulated mechanically. The average waveform of 30 evoked potentials was separated into an initial positive, a negative and a second positive component. During pairing of the skin and NBM stimuli, the area under the initial positive component was smaller than before or after pairing. The negative and second positive waves were unchanged. One minute after pairing, the initial positive wave returned to control values and continued to increase until the end of the experiment 50 min later, at which time it was 300% above control. The negative and second positive waves increased after the pairing to between 130 and 200% and remained at that level for the duration of the experiment. The effective NBM site for stimulation was the area rich in cholinergic neurons corresponding to the NBM. In control animals, repeated stimulation of the skin or NBM alone, or their random, unpaired stimulation together, did not enhance the somatosensory evoked potential. The results suggest that the NBM input enhances the efficacy of cortical responses to cutaneous input and thus may play a role in cortical neuronal plasticity. PMID- 1860052 TI - [31P]MRS study of the protective effects of prostaglandin oligomers on forebrain ischemia in rats. AB - Two ester-type prostaglandin oligomeric compounds were synthesized, one from prostaglandin E1 (termed MR-356) and the other from prostaglandin B2 (termed OC 5186). Using in vivo [31P]MRS, the protective effects of these oligomers on forebrain ischemia (15 min) were evaluated in a rat model. Forebrain ischemia caused a decrease in intracellular high energy phosphates and intracellular pH (pHi) in the control and compounds-treated groups, but changes of these values in the OC-5186-treated group were significantly smaller than those in the control group. Moreover, the cerebral energy metabolism of the OC-5186-treated group returned to the preischemia level more rapidly than in the control group after forebrain ischemia. MR-356 had some effects, but the differences were not significant. PMID- 1860053 TI - Increase in basic fibroblast growth factor-like immunoreactivity in rat brain after forebrain ischemia. AB - Using immunohistochemical techniques, a study was conducted to determine whether basic fibroblast growth factor (bFGF) is generated as one of the 'self-repair' responses in rat brain following transient forebrain ischemia. In normal brain, slight bFGF-like immunoreactivity was observed. However, in rats exposed to 20 min of forebrain ischemia, intense bFGF-like immunoreactivity was observed in the CA1 subfield of the hippocampus and the caudate putamen, and marked activity was evident in the temporal cortex, corpus callosum and the CA4 subfield of the hippocampus. Marked neuronal degeneration was also observed in these brain regions following forebrain ischemia. These results suggest that induction of bFGF-like immunoreactivity may be related to the healing which follows brain ischemia. PMID- 1860054 TI - Development of changes in endogenous GABA release during kindling epileptogenesis in rat hippocampus. AB - The calcium-dependent gamma-aminobutyric acid (GABA) and glutamate release from rat hippocampal CA1 slices, evoked by a 1-min depolarization with 50 mM K+, was investigated in different stages of kindling epileptogenesis. Kindling was induced by tetanic stimulation of the Schaffer collateral/commissural pathway. In agreement with our previous results, we found a significantly increased calcium dependent GABA release compared to that of implanted controls, in a group of fully kindled animals 1 day after the last seizure and also 25-36 days after the last seizure. In addition, we found that the increase in GABA release was associated with late phases of kindling epileptogenesis since no significant alterations were found in partly kindled animals that had received only 6 kindling stimulations while a significant increase was apparent in animals that had received 14 tetanic stimuli. When the release protocol was carried out in the presence of SK&F 89776-A, a blocker of the GABA uptake carrier, an additional amount of GABA was found after depolarization. This additional amount of GABA, reflecting the amount of GABA taken up under conditions without blocker, was in kindled animals not different from controls which demonstrates that a reduced GABA uptake does not account for the observed enhanced release in kindled animals. The calcium-dependent release of glutamate evoked by 1 min of high potassium depolarization was not significantly changed in the kindled groups. Only after prolonged depolarization during 4 subsequent minutes a significant increase in animals of the fully kindled group and at long-term after kindling was observed. The threshold K+ concentration for eliciting a calcium-dependent release of GABA and glutamate, was not changed in the kindled animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860055 TI - Tumor necrosis factor facilitates regeneration of injured central nervous system axons. AB - The results of this study attribute to tumor necrosis factor (TNF) a role in regeneration of injured mammalian central nervous system (CNS) axons which grow into their own degenerating environment. This is the first time that a specific factor involved in axonal regeneration has been identified. The axonal environment is occupied mostly by glia cells, i.e., astrocytes and oligodendrocytes. Previous studies have shown that mature oligodendrocytes are inhibitory to axonal growth. Therefore, it seemed likely that application of a factor such as TNF, which has been shown to be cytotoxic to oligodendrocytes, would contribute to the creation of permissive conditions for axonal regeneration. In the present work, injured adult rabbit optic nerves were treated with human recombinant TNF (rhTNF). As a result, abundant newly growing axons (circa 9000, about 4% of the total estimated number of axons in an intact adult rabbit) were observed traversing the site of injury. PMID- 1860056 TI - Corticotropin releasing factor antagonist reduces ischemic hippocampal neuronal injury. AB - This experiment tested the hypothesis that corticotropin-releasing factor (CRF) contributes to hippocampal ischemic injury. The antagonist to CRF (alpha-CRF) was administered intraventricularly 15 min prior to 10 min of transient forebrain ischemia in the Wistar rat. alpha-CRF demonstrated a neuroprotective effect in a dose-dependent manner most notable in CA1. There was also an increase in postischemic EEG recovery. It is postulated that CRF contributes to hippocampal ischemic injury through increased neuronal activity. PMID- 1860057 TI - Long-term cultured neurons from rat suprachiasmatic nucleus retain the capacity for circadian oscillation of vasopressin release. AB - We have developed a dissociated suprachiasmatic nucleus (SCN) cell culture system in order to begin a cellular analysis of the mammalian circadian oscillator. Monolayer-cultured neurons prepared from the SCN regions of 1-day-old rats were maintained in serum-free culture medium for 3-4 weeks and then perfused. In 12 out of 40 wells, a circadian oscillation of vasopressin release persisted for at least 4-5 cycles until the end of the perfusion period with no damping of the amplitude. This finding suggests that cultured SCN neurons retain the capacity for circadian oscillation for a long time, and should provide a useful model for the analysis of a mammalian circadian system at the cellular level. PMID- 1860058 TI - Cocaine-induced behavioral sensitization is not associated with loss of GABA immunoreactive neurons in the amygdala. AB - We investigated whether cocaine-induced behavioral sensitization (15 mg/kg, twice daily for 7 days) is associated with changes in gamma-aminobutyric acid (GABA) neurons in the lateral-basolateral amygdala of male Sprague-Dawley rats. The number of GABA-immunoreactive neurons in the amygdala did not differ between cocaine- and saline-treated rats. Although some aspects of this behavioral phenomenon parallel the kindling model of epilepsy, limbic alterations in GABA neurons do not appear to be associated with behavioral sensitization to cocaine. PMID- 1860059 TI - Activation of substantia nigra pars reticulata neurons: role in the initiation and behavioral expression of kindled seizures. AB - Numerous studies have implicated the substantia nigra pars reticulata (SNR) in the initiation and behavioral expression of kindled seizures. In immobilized, amygdala-kindled animals, SNR neurons have been shown to enter an intense burst firing pattern during afterdischarge (AD). Taken together these findings raised the possibility that the SNR facilitates the expression of kindled seizures by directly propagating seizure activity into target structures. In this study we examined the relationship between activation of SNR neurons and the electrical (EEG) and behavioral (clonic motor) expression of kindled seizures using both immobilized and unrestrained animals. The principal findings were that: (1) in both immobilized and unrestrained animals the SNR neurons of kindled, but not control, animals were recruited into a burst-firing pattern during AD; (2) the onset of burst-firing was delayed until after the onset of AD; and (3) the onset of burst-firing was not correlated with the onset of rhythmic motor seizure activity. These findings support the idea that the development of kindling is associated with recruitment of SNR neurons into a seizure propagating network. However, these data suggest that activation of SNR neurons is not necessary for the expression of clonic motor activity and does not lower seizure threshold. PMID- 1860060 TI - A cholinergic innervation of the bovine pineal gland visualized by immunohistochemical detection of choline acetyltransferase-immunoreactive nerve fibers. AB - An immunohistochemical investigation of the bovine pineal gland was performed using both a rabbit polyclonal antibody and a rat monoclonal antibody against choline acetyltransferase (ChAT). A network of ChAT-immunoreactive (IR) nerve fibers was located throughout the pineal gland, both in the perivascular spaces and between the pinealocytes. Most of the intrapineal ChAT-IR nerve fibers were endowed with varicosities. In addition, some ChAT-IR intrapineal neurons were found, often located at the base of the gland near the pineal recess. Within the habenular nucleus and pineal stalk, ChAT-IR perikarya and nerve fibers were also present. Some of these fibers projected towards the pineal gland. A number of ChAT-IR nerves were also located in the posterior commissure and could be followed into the gland. At the caudal tip of the pineal gland, a bundle of ChAT IR nerve fibers was observed to penetrate into the gland together with blood vessels. The presence of a cholinergic innervation of the bovine pineal gland, together with previous demonstration of the presence of choline acetyltransferase and muscarinic receptor binding sites in the bovine pineal gland, indicates a functional influence of a cholinergic nervous system on the pinealocyte. PMID- 1860061 TI - Tricyclic antidepressants inhibit Ca(2+)-activated K(+)-efflux in cultured spinal cord neurons. AB - The effect of tricyclic antidepressants and monoamine oxidase inhibotors on the Ca(2+)-activated K(+)-efflux was studied using 86Rb-efflux assay in primary cultured mouse spinal cord neurons. Depolarization of the cultured cells with 100 mM KCl increased the 86Rb-efflux significantly in Ca(2+)-containing buffer, but not in Ca(2+)-free buffer. All the antidepressants examined, except the monoamine oxidase inhibitors, inhibited the 86Rb-efflux. Desipramine exhibited additivity with tetraethyl ammonium (TEA) and quinine sulfate (QSO4), but not with GABAB receptor agonist baclofen. The inhibitory action of antidepressants was not mediated through the GABAB receptors, since GABAB receptor antagonist, phaclofen, was unable to antagonize this effect. The ability of tricyclic antidepressants to inhibit calcium ionophore (A 23187)-induced 86Rb-efflux suggests that these drugs do not act at the level of voltage-gated Ca(2+)-channels. Furthermore, this effect does not seem to involve the G-proteins, adenylate cyclase, or protein kinase C systems, since pertussis toxin (PTX) and the activators of adenylate cyclase and protein kinase C did not reverse the effect of tricyclics on 86Rb efflux. Taken together, these results suggest that antidepressants inhibit Ca(2+) activated K(+)-channels at a stage subsequent to the voltage-gated Ca(2+) channels. PMID- 1860063 TI - Effects of central injection of glucose on thermogenesis in normal, VMH-lesioned and genetically obese rats. AB - Intra-cerebroventricular (i.c.v.) injection of glucose (0.1-1.0 mumol) caused dose-dependent increases in resting oxygen consumption (Vo2) of conscious rats (maximum increase of 15.4 +/- 2% at 0.5 mumol). These effects were significantly attenuated by peripheral (i.p.) pretreatment with the beta-adrenoceptor propranolol, indicating the importance of the sympathetic nervous system (SNS) in the response. Plasma glucose concentrations were elevated (11%) 30 min after central injection of glucose, but intravenous glucose (0.5 mumol) did not affect resting Vo2. Animals which had been fasted for 12 h prior to Vo2 measurement exhibited reduced basal Vo2 values, but the nutritional state of the animal did not affect the metabolic response to central injections of glucose (0.5 mumol). Rats exhibiting genetic (fa/fa Zucker rats) and hypothalamic (VMH-lesioned) obesity showed similar thermogenic responses to centrally administered glucose, to their lean counterparts. These data suggest a dual action of central glucose in the regulation of energy balance, involving stimulation of energy expenditure in addition to its reported inhibition of energy intake. The defective diet induced thermogenesis associated with VMH and genetic obesities does not appear to result from an inability to respond to changes in intracerebroventricular glucose concentrations. PMID- 1860062 TI - Hippocampal mossy fiber zinc deficit in mice genetically selected for ethanol withdrawal seizure susceptibility. AB - Hippocampal mossy fiber zinc was examined in mice selectively bred for differences in susceptibility to handling-induced convulsions during ethanol withdrawal. The density of mossy fiber zinc in the CA3 stratum lucidum was significantly decreased in the duplicate lines of untreated withdrawal seizure prone (WSP) mice compared to untreated withdrawal seizure resistant (WSR) mice. Mossy fiber zinc densities in randomly bred control lines of mice (WSC) were intermediate to WSP and WSR mice. Serum, whole brain and whole hippocampal zinc were not significantly different between WSP and WSR mice, indicating that the reduction in the chelatable pool of hippocampal mossy fiber zinc was not a consequence of deficits in brain or whole body zinc nutrition. A highly significant correlation between hippocampal mossy fiber zinc density and handling induced convulsion indices suggests that a reduction in mossy fiber zinc may be one contributing factor in the expression of seizure susceptibility in WSP mice. PMID- 1860064 TI - Seasonal changes in methionine-enkephalin immunoreactivity in the brain of a hibernator, Spermophilus columbianus. AB - To identify the actual location of central endogenous opioid systems which may be involved in regulating the hibernation cycle, differences in the pattern of central methionine-enkephalin (Met-EK) immunoreactivity were compared between hibernating (body temperature, Tb = 7 degrees C) and non-hibernating (Tb = 37 degrees C) Columbian ground squirrels using the peroxidase-antiperoxidase technique. In non-hibernating animals, Met-EK-immunoreactive perikarya were observed in telencephalic (putamen, caudate nucleus, medial septum-diagonal band complex, amygdala) and diencephalic (periventricular hypothalamic nucleus, lateral hypothalamic area) regions, whereas immunoreactive fibers were found in the lateral septum, stria terminalis nucleus, various hypothalamic areas, arcuate nucleus, median eminence, thalamic intralaminar, periventricular nucleus and lateral habenular nucleus. Compared to the non-hibernating animal, a marked increase in the number of Met-EK-immunoreactive fibers was found in the lateral septal nucleus, the periventricular nucleus, the intralaminar thalamus and the paraventricular hypothalamus of hibernating ground squirrels. Since these changes in immunoreactivity were not observed in the artificially induced hypothermic ground squirrels (Tb = 7 degrees C), it is unlikely that the dissimilarity in immunoreactivity between animals from different hibernating phases is due to differences in their Tb. In combination with our previous studies, these results tend to suggest that hibernation may be brought about by an increase in endogenous opioid activity, especially in the lateral septal region. PMID- 1860065 TI - Lithium transport in the mouse brain. AB - Using the stable isotopes of lithium 6Li and 7Li, and the nuclear reaction 6Li(n,alpha)3H for detection, we have studied the isotopic exchange of lithium in various areas of the mouse brain and in the mouse plasma, under conditions of constant concentration of total lithium. The neutron irradiations were performed using 'cold' neutrons, at the European Institute Von Laue-Langevin. The nuclear reaction track densities were determined using an automatic image analyser. In the plasma, the isotopic ratios, 6Li/7Li, were measured using 'Secondary Ion Mass Spectrometry'. The concentration of total lithium in the plasma was kept close to 0.28 mM. The brain concentration of total lithium (referred to the tissue water content) ranged from more than 2 mM in the thalamus to less than 0.65 mM in the white matter of the cerebellum. The Nernst potential of lithium thus ranged from approx. -50 to approx. -20 mV, which means that lithium is probably not far from electrochemical equilibrium between brain cells and plasma. At any moment, the isotopic abundance of 6Li (ratio of 6Li to total lithium) in the different brain areas, were not significantly different from one another. The time-course of the isotopic abundance of 6Li in the brain was fitted by the composition of two exponential terms. The time-course of the isotopic abundance of 6Li in the plasma was also fitted by the composition of two exponential terms. These analytic curves (for the brain and for the plasma) were not significantly different from each other, at the precision of the measurements. This means that the isotopic equilibration of lithium between brain and plasma is almost instantaneous (i.e. accomplished in a few min at the most). PMID- 1860066 TI - Projections of the parvocellular reticular formation to the contralateral mesencephalic trigeminal nucleus in the rat. AB - Projections of the parvocellular reticular nucleus (PCRt) to the contralateral mesencephalic trigeminal nucleus (Me5) were studied in the rat with neurophysiological and neuroanatomical techniques. Three types of responses (classified by latencies) were recorded extracellularly in the Me5 area after electrical stimulation of the PCRt: (1) R1 fast unitary reactions (latency 0.2 0.5 ms) found throughout the entire caudal Me5 area; (2) R2 slower unitary reactions (latency 0.7-1.2 ms) recorded ventral and lateral to the caudal Me5; and (3) R3 compound potentials (latency 1.0-2.5 ms) recorded within the ventrocaudal Me5. Relayed or synaptic fields were not observed. Intracellular recordings of identified cell bodies of periodontal afferents, muscle spindle afferents and interneurones revealed no short-term postsynaptic potentials following PCRt stimulation. In some experiments jaw muscle spindle afferent activity was increased by PCRt stimulation and jaw-opening and jaw-closing reflexes were facilitated in the contralateral musculature. Neuroanatomical experiments, using Phaseolus vulgaris leucoagglutinin as an anterograde tracer, showed direct projections with intensive collateralization of PCRt fibres into the Me5 area. Synaptic contacts of PCRt fibres with primary afferent cell bodies were observed in the ventrocaudal parts of the Me5 only. The electrophysiological results are discussed in relation to the neuroanatomical findings. PMID- 1860067 TI - Release of gamma-[3H]aminobutyric acid from synaptosomes: effect of external cations and of ouabain. AB - In the present study we have investigated the effect of cations and ouabain on Ca(2+)-independent and Ca(2+)-dependent release of gamma-[3H]aminobutyric acid ([3H]GABA) from sheep brain synaptosomes. The presence of Na+ in the external medium is essential for the Ca(2+)-independent release induced by K+ or ouabain. Thus, in the absence of Ca2+, ouabain or K+ causes the release of [3H]GABA provided that Na+ is present in the external medium. Under K(+)-depolarizing conditions, in a Na+ medium, either ouabain or Ca2+ further increases the [3H]GABA release induced by depolarization, but their effects are not additive. The presence of external Na+ is not required for the Ca(2+)-dependent release of [3H]GABA due to K+ depolarization, and this release, which occurs in a choline medium, is not modified by ouabain. Under these conditions (choline medium) K(+) depolarization dependent release is absolutely dependent on external Ca2+, which suggests that this release of [3H]GABA occurs only by exocytosis, without the carrier-mediated efflux which normally co-exists with exocytosis due to K(+) depolarization in a Na+ medium. It is likely that the release induced by ouabain or K+ involves the membrane carrier which responds to changes in membrane potential. PMID- 1860068 TI - A postmortem study of brain nicotinic receptors in Parkinson's and Alzheimer's disease. AB - Brain nicotinic receptors were studied in the frontal cortex, temporal cortex, hippocampus and caudate nucleus in patients with Parkinson's disease (PD), Alzheimer's disease (AD) and control. The Bmax and Kd values of (-)-[3H]nicotine binding were determined with a Scatchard analysis. The number of nicotinic receptors declined both in PD and in AD patients in all brain areas examined. The Kd values were unchanged. There was a negative correlation between the degree of dementia in PD patients and the number of nicotinic receptors in the frontal cortex. A similar correlation was seen between the muscarinic/nicotinic receptor ratio in the frontal cortex and the degree of dementia in PD patients. The present findings indicate that nicotinic receptors are affected not only in AD, but also in PD and that dysfunction of the cholinergic system in the frontal cortex is involved in the dementia process in PD. PMID- 1860069 TI - Epidermal growth factor enhances short-term potentiation and facilitates induction of long-term potentiation in rat hippocampal slices. AB - Effects of recombinant human epidermal growth factor (hEGF) on short-term potentiation (STP) of evoked potential were investigated in Schaffer/commissural CA1 pyramidal cell synapses of rat hippocampal slices. Perfusion of hEGF (6-60 ng/ml) significantly enhanced the STP induced by shorter tetanus (11 impulses at 100 Hz) in a concentration-dependent manner and the effect resulted in generation of long-term potentiation (LTP). The results suggest that hEGF can activate the mechanisms related to induction of LTP. PMID- 1860070 TI - Glycine-like immunoreactivity in synaptic boutons of identified inhibitory interneurons in the mammalian spinal cord. AB - Glycine is thought to be a major inhibitory neurotransmitter in the mammalian CNS. Two types of physiologically identified interneurons, Renshaw cells and Ia inhibitory interneurons, were intracellularly stained with horseradish peroxidase, and their axon terminals were studied at the electron microscopic level. Post-embedding immunogold procedures were used to reveal the presence of glycine-like immunoreactivity. The synaptic terminals of both types of interneuron were significantly enriched with glycine-like immunoreactivity, providing support for the idea that glycine is a mediator of synaptic transmission in the recurrent and reciprocal inhibitory pathways to motoneurons. PMID- 1860071 TI - Delayed growth and maturation of astrocytic cultures following exposure to ethanol: electron microscopic observations. AB - This investigation examined the effects of ethanol on the morphologic features of cultured rat astrocytes using a treatment paradigm that provided consistent exposure to ethanol at concentrations of 0.2%, 0.5%, or 1.0% (w/v). Cultures were assessed between 4 and 8 days in vitro during the logarithmic phase of growth; differences in culture growth, cell profile area and ultrastructural configuration were found. A dose-dependent inhibition of culture growth was observed after 48 and 96 h of ethanol exposure. In control cultures, the consequences of culture growth included the progressive crowding of cells, a concomitant reduction in the cell profile area, and increased cell-cell contact. On culture day 8, electron microscopic examination of control cultures demonstrated a complex stratified cellular layer, the junction of cells by puncta adhaerentia and the acquisition of intermediate filament bundles. In contrast, the impaired growth in ethanol-exposed cultures was associated with the retention of an extensive cell profile area suggesting restrained morphologic development. At the electron microscopic level, ethanol-exposed cultures showed a dose dependent attenuation in both the depth and complexity of the cell layer. These findings indicated that the growth kinetics and morphologic development of astrocytic cultures are vulnerable to ethanol exposure at moderate and high levels. These findings were attributed to both ethanol cytotoxicity and a deprivation of cellular interaction resulting from the restricted population size. PMID- 1860072 TI - Cortical projection of putative group Ib afferent fibres from the human forearm. AB - The possibility was investigated that impulses in group Ib afferents from fore arm flexors have access to cerebral cortex in man. A long-lasting increase in the threshold (Th) of group Ia afferent fibres from flexor carpi radialis muscle (Fcr) was obtained after prolonged (100 Hz for 20 min) tendon vibration at the wrist. It was assumed that under this condition a weak electrical stimulation of the median nerve at the elbow, insufficient to reactivate Ia fibres because of the rise in their threshold (as verified by the method of homonymous Ia facilitation of Fcr H reflex), engaged Ib fibres only. Peripheral volleys at Erb's point and cerebral cortical potentials to median nerve stimulation at the elbow were evoked before and after prolonged vibration of Fcr. During 10-30 min after the end of vibration, in which homonymous facilitation of Fcr H reflex was abolished, both the ongoing peripheral volley and the cortical responses were markedly reduced with respect to their control values. Recovery to pre-vibration control amplitudes coincided with recovery of Fcr H reflex homonymous facilitation. In order to verify if activity in afferents other than group Ib fibres might contribute to the cortical response after vibration, specially designed experiments were also performed. It is concluded that the cortical wave recorded after 20 min vibration represents the arrival of Ib impulses from flexor carpi radialis to the human cerebral cortex. PMID- 1860073 TI - Life events-induced decrease of corticosteroid type I receptors is associated with reduced corticosterone feedback and enhanced vulnerability to amphetamine self-administration. AB - In this study, we attempted to find out whether a social stress-induced increase in the vulnerability to acquire amphetamine self-administration was associated with a change in number of hippocampal corticosteroid receptors. This was examined in two types of sex-mixed colonies of rats. Animals were maintained for 4 weeks in: (1) 'stable social condition', membership did not change after constitution of the colony; (2) 'unstable social condition', the males were changed daily in a random design. The animals living in the 'stable social' conditions had: (1) a lower number of hippocampal type I corticosteroid receptors; (2) a longer duration of the increase in plasma corticosterone after exposure to novelty; (3) a higher vulnerability to acquire amphetamine self administration. These findings suggest that a decrease in hippocampal type I corticosteroid receptors may be one of the biological mechanisms responsible for the impaired corticosterone feedback control observed in vulnerable animals. These findings throw more light on the role of hypothalamo-pituitary-adrenal axis in the modulation of adaptive behavior. The availability of drugs which are specific for corticosteroid receptors could represent a new approach to the therapy of certain behavioral disturbances. PMID- 1860074 TI - Excitatory amino acid antagonists (kynurenic acid and MK-801) attenuate the development of morphine tolerance in the rat. AB - To investigate the possible role of excitatory amino acids (EAAs) in the mechanisms of morphine tolerance, rats were treated either with the wide-spectrum EAA antagonist, kynurenic acid (150 mg/kg), or the specific N-methyl-D-aspartic acid (NMDA) receptor antagonist. MK-801 (0.05 mg/kg), during a four-day induction period of morphine tolerance. Morphine was given once daily at a dose of 15 mg kg. On the fifth day rats were injected only with morphine (15 mg/kg), and analgesia was assessed using the hot-plate test. Morphine tolerance was significantly reduced by both EAA antagonists. Control experiments showed that at the same doses neither acute nor chronic administration of these antagonists affected morphine analgesia itself in a manner that can explain these findings. The possible involvement of EAAs in the mechanisms of morphine tolerance is discussed. PMID- 1860075 TI - Age-related changes in junctional and non-junctional conductances in two electrically coupled peptidergic neurons of the mollusc Lymnaea stagnalis. AB - Age-related changes in electrotonic coupling ratio of two identified neurons in Lymnaea stagnalis were studied together with the underlying changes in the steady state conductance properties of the network. Two phases were distinguished in the development of coupling ratio across lifespan. During the first phase (age of 3 13 months), coupling ratio decreased from decreased from 60% to 30%. The second phase (age 13-20 months) was characterized by an increase in coupling ratio. Values of up to 60% were reached again in the oldest animals. Voltage clamp measurements showed that the biphasic trend of the age-related changes in coupling ratio is paralleled by changes in conductance properties of the junction between VD1 and RPD2. During the first phase junctional conductance decreased, whereas during the second phase junctional conductance increased. In addition to the decrease in junctional conductance, a growth-related increase in non junctional conductance of VD1 and RPD2 contributed to the decrease in coupling ratio observed during the first phase. Thus our results indicate that in Lymnaea junctional connections between neurons may undergo considerable and discontinuous changes after sexual maturation. In addition to these changes in steady-state electrical properties, indications were obtained that age-related changes of kinetically slower conductance(s) may occur in the non-junctional membrane of VD1 and RPD2. PMID- 1860076 TI - Reversal of learning impairment in ventral globus pallidus-lesioned rats by combination of continuous intracerebroventricular choline infusion and oral cholinergic drug administration. AB - The effects of separate or combined oral administration of THA (9-amino-1,2,3,4 tetrahydroacridine hydrochloride) and NIK-247 (9-amino-2,3,5,6,7,8-hexahydro-1H cyclopenta[b] quinoline monohydrate hydrochloride) and intracerebroventricular choline infusion using an osmotic minipump were investigated by observing locomotor activity, shock sensitivity, passive avoidance response and cerebral choline and acetylcholine contents in the bilateral ventral globus pallidus lesioned rat. Evaluation of locomotor activity and shock sensitivity revealed no sensorimotor disturbances caused by combined administration. Intracerebroventricular choline infusion (100 mumol/day) and oral THA or NIK-247 administration (0.5 mg/kg) had no effect on the acquisition of the passive avoidance response, while the combination of oral THA or NIK-247 administration (0.5 mg/kg) and intracerebroventricular choline infusion (100 mumol/day) elicited good acquisition of passive avoidance learning and produced a significant increase of choline and acetylcholine in the cerebral cortex of the bilateral ventral globus pallidus-lesioned rat. These findings suggest that continuous intracerebroventricular choline infusion may intensify the ameliorating effect of THA or NIK-247 on learning disturbance. PMID- 1860077 TI - [Complete removable dentures and prognathism]. AB - Further to some reminders concerning terminology and resorption, this article presents the full denture prosthetic treatment for two patients with total edentation and a prognathic malocclusion. The first case presents a tridimensional symptomatology, described by: a progeny; a voluminous mandibular terrain; a concave profile; a rather closed mandibular angle; a mandible ridge which circumscribes the upper jaw; The particularities of the prosthetic treatment in this case are: a lowering of the posterior occlusal plane; a mounting of the teeth in a limited external position, that is to say, the maxillary lingual cuspids and the mandibular mesio-distal groove on the inter crest line; the mandibular incisors and cuspids placed with a lingual inclination to obtain an edge-to-edge occlusal contact. The second case is of vertical symptomatology type, described by: a macrogeny; a moderate concavity of the profile; a very marked increase of the vertical dimension; an open mandibular angle; a short ramus; a long mandibule; a very marked overjet between the anterior crests. The particularities of the prosthetic treatment for this case are: a posterior teeth placement, avoiding cross-bite position, taken into account the strong convergence of the intercrest lines; a strong lingual inclination of the mandibular incisors and cuspids, in order to obtain an edge-to edge occlusal contact. In the light of these two specific cases, emphasis is placed on the particularities of the treatment and on the teeth placement proposed in order to avoid any cross-bite teeth mounting. PMID- 1860078 TI - [Dental-prosthetic margin in bonded esthetic restorations. Clinical aspects]. AB - The long term success of any bonded prosthesis mainly depends on the quality of the marginal adaptation. Its degradation has been noted both at the clinical and the experimental levels. It may be due to biological, chemico-physical, mechanical and clinical factors. Improving the marginal gap closure is based on some principles: the type of preparations on which depends the stabilisation and the good positioning of the restorations; the quality of the clinical isolation which will avoid any humidity on the bonded surfaces (saliva, blood, gingival fluids); the chemical and physical type of the bonding polymer and the quality of its polymerisation; the finishing and final surface condition directly related to the kind of finishing burs used. The understanding and application of these few clinical principles enable the practitioner to expect a better clinical result as regards the bonding of aesthetic restorations. PMID- 1860079 TI - [Mastication and the electromyographic silent period in denture wearers]. AB - The purpose of this study is to compare the masticatory efficiency and the physiological activity of masticatory muscles among patients with removable partial dentures (R.P.D.) and patients with natural dentition. The masticatory efficiency is assessed from the duration of chewing sequences for various foods, from the first masticatory cycle to the swallowing. The physiological activity is tested by the duration of the inhibition reflex called the "silent period" (S.P.) obtained upon each muscle examined: 29 subjects are examined, 24 of them had a R.P.D.; they were divided into four groups according to the extent of their edentation; 5 control subjects have full natural dentition. The study is performed using global electromyography of the two masseter muscles and the two anterior temporal muscles. The mastication of the control subjects appears to have a regular alternance of working potential and periods of rest. The duration of the chewing sequences is determined by the nature of the food, brief for soft food, long for hard food. The mastication of patients with R.P.D. appears more irregular with a lengthening of active phases. The duration of chewing sequences is significantly longer for the control subjects. The duration of the S.P. is 19 21 milliseconds for the masseter muscles of the patients with dentures and the control patients, and 20-22 milliseconds for the temporal muscles for the same individuals. The differences of the S.P. durations between control subjects and patients with R.P.D. is never significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860080 TI - [Original method for total edentulous rehabilitation based on Ludwigs technique. 3. Final impression and functional record of intermaxillary relations]. AB - In the technique described, the search for the peripheral joint and the final impressions are really functional and rely on adapted silicone impression materials. The vertical dimension is investigated physiologically (speech/swallowing). The recording of the centric relation is confirmed graphically with a centric pin. Thus, the patient transcribes his "occlusal signature" and provides both the practitioner and the dental technician with precise data for the mounting of denture teeth. PMID- 1860081 TI - [Rationale for fabrication of combination dentures]. AB - The complexity of this type of restoration comes from the numerous clinical and laboratory steps required. Achievement of these prosthodontic restoration is based on a careful clinical examination, models mounted on an articulator, in centered relation and adequate vertical dimension. The models allow the surveyor examination, the teeth set up and/or wax up. Duplication of the teeth set up in acrylic will reduce the number of patient's appointments, and thus, the potential errors will be minimized. This acrylic teeth set up (A.T.S.) will allow: to keep the decided occlusal relationships; to visualize the teeth grinding to be made; to guide the tooth preparation; to take the abutment impression, in occlusion. Therefore: the final model; the vertical dimension; occlusal relationship; the aesthetic; and, the removable partial denture design will be available for the dental technician. Furthermore, in close to full denture cases (class I and large class IV), the A.T.S. can be used to take the impression, to achieve the framework, and to transfer the occlusal registration. PMID- 1860082 TI - [Scanner placement guide and surgical guide in implantology]. AB - The pre-surgical investigation may provide added information by the wearing of a detection cad-can indicating the axes of the future implants at the time of the cad-can examination. This stent is made, using a polymerised director mounting, equipped with radio-opaque detectors in aluminium or zinc oxyphosphate sealing cement. The resulted illustration facilitates the concentration between the surgeon and the prosthetist in the definitive choice of the site of implantation. The plaster model, used for the making of the detection cad-can, is used to transfer this information. In the clinic, the latter is supported by a surgical stent. This guide includes: an indexed stabilising portion on the remaining teeth or portions of edentated crest not involved in the surgery; guiding tubes with a diameter of 2.1 mm, made of infiltrated aluminium according to the INCERAM* procedure. The detection cad-can and surgical stent unit permit a correlation between the preimplant investigation phase and the surgery. PMID- 1860083 TI - [Use of telescopes for rehabilitation with removable dentures. 2. Clinical examples]. AB - The purpose of these clinical cases is to show the advantages of coping abutments in fixed and removable partial denture reconstructions. These cases try to gather the largest indications for this technique. The emphasis is put on many positive points of this type of reconstruction: control and easy maintenance via an optimal accessibility to the abutments; may be used in complex rehabilitations combined with other types of attachments; easy insertion of the removable partial denture by the patient; improvement in the prognosis for cases that cannot be treated with fixed prosthodontics and precision attachments. A good aesthetic result can be achieved and gives expectation for an encouraging future for this type of well-made reconstruction. PMID- 1860084 TI - A new dimension of negligence? PMID- 1860085 TI - Prophy fees. PMID- 1860086 TI - In-Ceram bridges natural translucence and strength--without metal. PMID- 1860087 TI - Thy daily bread. PMID- 1860088 TI - An open letter to professionals from someone infected with HIV. PMID- 1860089 TI - A study of the reasons for tooth extraction in a Canadian population sample. AB - The reasons for extraction of teeth were determined in a Canadian population sample of 909 patients, ranging in age from 14 to 91 years. Caries was the primary cause of extraction (63%), followed by periodontitis (34%). For the adult age groups, the percentages were approximately the same. While periodontitis was the cause of one-third of the extractions, these occurred in only one-fifth of the population. Although there is a commonly expressed belief that periodontitis is the major cause of tooth loss in adults, a review of both historical and contemporary literature does not support this position. According to the current concept of the natural history of periodontal disease, only about one-fifth of the population, or less, is likely to have periodontitis severe enough to cause tooth loss. This view is consistent with data from this and most other studies on the reasons for tooth extraction. PMID- 1860090 TI - Root surface caries prevalence and associated factors among adult patients in an acute care hospital. AB - There have been many studies reporting on the prevalence of root surface caries in elderly populations, but there is little consistency in these reports concerning the associated risk factors. In the present study, intraoral examinations were carried out on adult patients (age range 22 to 91 years, mean age 57.9) on the acute care wards of a teaching hospital. Of the 103 patients examined, 23.3% exhibited carious lesions on root surfaces, these lesions occurring more frequently in males than in females, and more frequently in the 60 years and older age groups. Forty-five per cent of all root lesions recorded were found on the buccal or facial root surfaces of teeth exhibiting root surface caries. Individuals exhibiting root surface caries had more surfaces with gingival recession and loss of attachment greater than or equal to 3mm, more retained roots, higher DMFT values, and less teeth. However, statistically significant relationships were not obtained between root surface caries and a) coronal caries, b) dental plaque, c) calculus, d) bleeding on probing, and e) probing depth greater than or equal to 4mm. Thirty-three strains of Actinomyces viscosus were isolated from plaque samples taken from root surface lesions compared to 21 strains isolated from intact root surfaces. PMID- 1860091 TI - Reversible tricuspid regurgitation in a patient undergoing treatment for acute leukemia. AB - A 52-year-old female patient treated for acute lymphoblastic leukemia with combination chemotherapy (cyclophosphamide, vincristine, adriamycin and prednisone), broad spectrum antibiotics and amphotericin via a Hickman catheter placed in the superior vena cava, developed echocardiographically confirmed tricuspid regurgitation. A second admission four months later showed only mild tricuspid regurgitation. The authors conclude that the amphotericin given via the central line caused valvulitis of the tricuspid valve. PMID- 1860092 TI - Assigning priority to patients requiring coronary revascularization: consensus principles from a panel of cardiologists and cardiac surgeons. AB - In light of lengthy waiting lists for coronary surgery in Canada, a panel of 16 cardiologists and cardiac surgeons was convened to derive guiding principles for ranking how urgently diverse patients with angiographically proven coronary disease require revascularization. Factors likely to affect urgency were agreed upon by the panelists and incorporated into a case scenario questionnaire. Each panelist then rated 438 case scenarios with respect to maximum acceptable waiting time on a scale with seven time frames ranging from emergency surgery ('level 1') to delays of up to six months ('level 7'). The scenario rating process facilitated attainment of a panel consensus. The purpose of the principles is to assist in assigning priorities to patients according to both symptoms and risk of death or additional morbidity from ischemic events. The pattern or severity of the patient's anginal symptoms and the response of those symptoms to medical therapy emerged as the single most important determinant of the level of urgency. Anatomy and noninvasive tests of ischemic risk were the other key determinants of priority. All other factors were less important, and operated largely within a given level of urgency on the seven-point scale. The principles, including explicit ranking criteria divided according to angina class, are outlined in this final report. The panel specifically cautioned that adoption of such principles is not designed to countenance delays in treatment, but if necessary, should help form more rational queues for coronary revascularization. PMID- 1860093 TI - Converting enzyme inhibition attenuates the noradrenaline response to the Valsalva maneuvre. AB - HYPOTHESIS: Reduction of plasma angiotensin II inhibits release of noradrenaline in response to a sympathetic nervous system stimulus. OBJECTIVE: To compare heart rate and plasma catecholamine responses to the Valsalva maneuvre before and after inhibition of angiotensin converting enzyme. DESIGN: Four weeks of placebo (all patients). If sitting diastolic blood pressure was found to be between 100 and 115 mmHg, then double-blind randomization to receive 2.5, 5, 10 or 20 mg of quinapril bid for a further four weeks. SETTING: Ambulatory hypertension clinic with admission to clinical investigation unit overnight for interventions. PATIENTS: Uncomplicated essential hypertensives of English-Irish ancestry. Twenty five eligible patients completed the study, while three additional patients withdrew early. INTERVENTIONS: Blood pressure and heart rate were monitored weekly during placebo, and biweekly during active treatment. Patients were rehearsed in performance of the Valsalva maneuvre. At the end of the placebo and active therapy phases, each patient performed standard Valsalva maneuvres immediately before and 2 h after the morning dose of placebo or active drug. Heart rate was recorded continuously throughout the maneuvre, while blood was sampled for catecholamine determinations prior to the start of straining and again approximately 10 s following the end of straining. MAIN RESULTS: Heart rate responses to the Valsalva maneuvre were not affected by acute administration of quinapril, but a slight attenuation of the tachycardic response was seen after four weeks of therapy (P less than 0.05). An increase in plasma noradrenaline concentration associated with the straining phase of the Valsalva maneuvre was markedly attenuated after both acute and chronic quinapril therapy (P less than 0.01). CONCLUSION: By blocking biosynthesis of angiotensin II, converting enzyme inhibition may attenuate baroreceptor-stimulated release of noradrenaline. PMID- 1860094 TI - Efficacy of once daily nitrendipine in mild hypertension: comparison with placebo. AB - A randomized, double-blind, parallel group study was carried out to compare the antihypertensive efficacy of nitrendipine with that of placebo in 80 mild hypertensives. The dose of nitrendipine was initially 10 mg once daily and was doubled to 20 mg once daily after four weeks in patients who responded poorly (33% of patients on nitrendipine and 49% of patients on placebo required doubling of dose). Blood pressure was assessed 20 to 24 h after dosing. Mean (+/- standard error) reductions in supine systolic and diastolic blood pressures for patients who completed 10 weeks of therapy were significantly greater for the nitrendipine group than for the placebo group (systolic blood pressure 18.1 +/- 2.7 mmHg versus 4.2 +/- 2.5, P less than 0.0001; and diastolic blood pressure 10.6 +/- 1.1 mmHg versus 6.6 +/- 1.3, P = 0.002). A comparison of mean reductions in standing systolic and diastolic blood pressures produced similar results. Goal of therapy (diastolic blood pressure no more than 90 mmHg or reduction of at least 10 mmHg) was achieved in 71% of nitrendipine-treated and 45% of placebo-treated patients (P less than 0.05). Nine of 80 patients randomized to therapy dropped out during treatment (nitrendipine: four adverse experiences and one moved from the area; placebo: two adverse experiences, and drug ineffective in two). Overall, the incidence of adverse experiences considered by the physician to be related to treatment was higher in the placebo group (32%) than in the nitrendipine group (23%). Only flushing had a higher incidence in the nitrendipine group; however, the overall incidence was low (9%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860095 TI - Neutrophil oxygen free radical production proportionates with the degree of myocardial ischemia. AB - OBJECTIVE: To assess the production of oxygen free radicals by chemiluminescence and to assess leukocyte aggregation, in patients with acute myocardial infarction and angina pectoris, and to compare these to creatine kinase-MB levels. DESIGN: Prospective study with serial estimation at presentation and 72 h later. SETTING: Referral, tertiary care hospital. PATIENTS: Group 1, acute myocardial infarction (n = 18); group 2, stable angina pectoris (n = 8); and age-and sex-matched normal healthy persons (n = 12). All patients included had pain of less than 24 h duration with typical electrocardiographic and laboratory abnormalities. Patients or controls who had any inflammatory disease in the preceding two weeks or who were on anti-inflammatory drugs, calcium channel or beta-adrenoceptor blockers, were excluded. TESTS: Venous blood samples taken at presentation and 72 h later were analyzed for creatine kinase-MB using a standard kit, neutrophilic chemiluminescence and leukocyte aggregation. MAIN RESULTS: In group 1 there were significant rises in both creatine kinase-MB and chemiluminescence, which subsequently regressed (P less than 0.02). There was, however, no statistical correlation between the two. The qualitative pattern of the rise and fall of chemiluminescence was similar in group 2. Changes in leukergy in both groups were not significant. CONCLUSIONS: Oxygen free radical generation occurs early in myocardial ischemia with regression by 72 h. Neutrophilic chemiluminescence may provide an alternative method for assessment of myocardial ischemia. PMID- 1860096 TI - Development of the coronary vasculature in hypoxic fetal rats treated with a purified perfluorocarbon emulsion. AB - OBJECTIVE: To quantitatively define the coronary vascular bed in the 21-day-old rat fetus with gestational normoxia and hypoxia; to determine if maternal supplemental oxygen and/or oxygen-carrying perfluorocarbons (PFCs) influence development of coronary vessels; and to compare the results using purified and unpurified PFC treatment. DESIGN: Unilateral uterine artery ligation was introduced on gestational day 17 in pregnant animals. Control fetuses were from unligated uterine horns. Experimental intervention occurred during gestational days 17 to 21, with fetuses recovered on day 21. Developing coronary vessels were analyzed quantitatively via light microscopy. ANIMALS: Pregnant Sprague Dawley rats. INTERVENTIONS: Following ligation, pregnant rats received no further treatment, supplemental oxygen inhalation alone, or daily intravenous purified PFC treatment, with or without supplemental oxygen. MAIN RESULTS: Hypoxia caused an increase in resorptions (P less than 0.001), and decreased fetal body weight (P less than 0.001) and heart weight (P less than 0.05). Although the area occupied by developing coronary vessels (sinusoids) was substantially increased, maturation was unchanged. Oxygen supplementation alone did not appreciably influence fetal resorptions or body weight in ligated horns, but did increase fetal heart weight. Sinusoidal area decreased (P less than 0.01), with no effect on sinusoidal maturity. Purified PFC treatment did not alter maternal weight gain or fetal body weight, and moderately decreased resorptions in ligated horns. Fetal heart weight was augmented with purified perflurochemical, while unpurified perfluorochemical treatment diminished heart weight. Both PFC emulsions substantially decreased sinusoidal area. CONCLUSIONS: Perflurocarbon treatment associated with supplemental oxygen is capable of improving the hypoxic effects on fetal heart and coronary vessel development if the emulsion used is appropriately purified. PMID- 1860097 TI - Phototherapy for neonatal hyperbilirubinemia. PMID- 1860098 TI - Wife assault: physicians cannot ignore it. PMID- 1860099 TI - Megavitamin and megamineral therapy in childhood. PMID- 1860100 TI - The fee-for-service system should be replaced. PMID- 1860101 TI - Food safety. PMID- 1860102 TI - Hemodynamic monitoring: a technology assessment. Technology Subcommittee of the Working Group on Critical Care, Ontario Ministry of Health. AB - OBJECTIVE: To review catheterization of the right side of the heart according to technical capability, diagnostic accuracy, range of possible uses, therapeutic impact, benefit to patient outcome and impact on health care workers. DATA SOURCES: MEDLINE was searched for English-language articles published since 1962. Additional references were selected from the bibliographies of identified articles. STUDY SELECTION: Nonrandomized trials and retrospective reviews were included because of a paucity of randomized controlled trials. DATA EXTRACTION AND SYNTHESIS: After a review of the data on hemodynamic monitoring by the subcommittee members, guidelines were developed through the use of the nominal group and Delphi consensus-gathering techniques. CONCLUSIONS: The use of catheterization of the right side of the heart for hemodynamic monitoring should be reserved for tertiary and secondary care hospitals, which are adequately staffed by physicians and nurses well versed in the use of such monitoring. Future research should be directed at determining whether the use of hemodynamic monitoring will improve outcomes among patients, especially those with myocardial infarction, septic shock or pulmonary edema. PMID- 1860103 TI - Anaerobic vertebral osteomyelitis. PMID- 1860105 TI - Notification of tuberculosis. PMID- 1860104 TI - Insulin treatment, NIDDM and atherosclerosis. PMID- 1860106 TI - Interest heavy as Canada's HIV and AIDS researchers form own organization. PMID- 1860107 TI - AIDS project spawns controversy, not results. PMID- 1860108 TI - Canada is unfair to medical immigrants. PMID- 1860109 TI - Health care problems in Ontario. PMID- 1860110 TI - Melanin pigmentation disorders of the skin and oral mucosa. AB - Pigmented lesions in brown, blue-black, or variations of these colors are relatively rare in the oral cavity but very common in the skin and can range from absolutely benign to highly malignant. The differential diagnosis of brown and blue-black lesions of the oral cavity includes normal racial pigmentation, melanosis, nevi, melanoma, amalgam tattoos, and disorders related to the blood or blood vessels. PMID- 1860111 TI - Compromise and control of the airway. AB - Compromise of the airway is a preventable cause of patient death and is of vital concern to the dental professional. The dentist may encounter airway compromise and must be able to render appropriate care. Unfortunately, this important topic has received little or no attention in the dental literature during the last 5 years. The purpose of this article is to review the etiology of airway compromise, the basic principles of airway management, and the indications for more advanced airway intervention, including intubation and emergency surgical approaches. PMID- 1860112 TI - Microwave processing of permanent soft denture liners. AB - This article describes a technique of processing a resilient soft denture liner using microwave irradiation. The technique employs a specially designed flask that can be heated in a microwave oven. The flask can be either fabricated using commonly available dental laboratory materials or purchased commercially. The microwave polymerization of the resilient soft denture liner reduces the potential warpage of the denture base that can occur during the conventional process of boiling in water for 2 hours. Additionally, microwave irradiation reduces processing time to less than 1 hour, allowing the dentist the opportunity to reline a patient's denture in a single visit. The technique is simple and requires no extensive or elaborate dental laboratory equipment. PMID- 1860113 TI - Malposed sublingual gland in the anterior mandible: a variant of Stafne's idiopathic bone cavity. AB - This article reports a case of an asymptomatic, ill-defined radiolucency in the anterior mandible in the region of the central and lateral incisor teeth, found on routine roentgenographic examination. A labial mucoperiosteal flap was raised under local anesthesia. A portion of the lingual plate and inferior border of the anterior mandible were missing, and the space was occupied by the sublingual gland extension. The entrapped sublingual gland was removed and the histological diagnosis confirmed. The mucoperiosteal flap was sutured back in position. Healing was uneventful. PMID- 1860115 TI - The team approach to intermaxillary fixation. AB - A series of lawsuits for negligence was filed against a dentist who failed to consult with the family physician and other health-care providers before instituting intermaxillary fixation for the control of obesity. Additional allegations were lack of informed consent and lack of proper care. This article presents the case report, with emphasis on its physical, emotional, and legal outcome. PMID- 1860114 TI - The many faces of adult leukemia. AB - This article describes the facial complications of adult leukemia, as derived from a study of more than 3,000 patients treated at the University of Texas M.D. Anderson Hospital during the past 25 years. Facial leukemia cutis, leukemia associated facial hemorrhages, leukemia-induced cranial nerve facial palsies, and leukemia-provoked pure and mixed facial infections are discussed. PMID- 1860116 TI - Quality assurance and continuing education: point/counterpoint discussion. PMID- 1860117 TI - Unremitting pain to the mandible secondary to metastatic breast cancer: a case report. AB - The most common site of distant primary tumor metastasis to the jaw bones is the breast. The clinical signs and symptoms, and radiographic appearance of these lesions can be extremely variable. Histologic examination, however, will usually resemble the tissue from the primary tumor. In the case presented, the biopsy specimen was consistent with adenocarcinoma of the breast. PMID- 1860118 TI - Thielemann's diagonal law of occlusion revisited. AB - Thielemann's studies of malocclusal relationships and the frequently observed chain reactions created in distant localities led to the formulation of a philosophical approach to occlusion that is also of practical premeditative clinical relevance for the practitioner. Dr. Thielemann presumed to name it a law, and repeated clinical observations apparently support and reinforce his claim. All disciplines of dentistry inevitably encounter and need to know about this aspect of fission-reactive involvement with the common and seemingly innocuous malocclusions. By incorporating the law into the diagnostic, planning, corrective, and therapeutic stages of treatment, the clinician can readily categorize patients for needs assessments and future goals in treatment. PMID- 1860120 TI - Theme 3: Mainframing dentistry. Article 1: New risks, responsibilities, and profits for the dental schools. PMID- 1860119 TI - A renaissance Afro-American of the 19th century: Dr. John S. Rock. PMID- 1860121 TI - A composite resin veneer occlusal surface on an overlay partial denture. AB - The purpose of this article is to illustrate a technique adapting a light-curing composite resin veneer and an opaquing medium with chemical adhesion properties to a partial denture framework in a patient with severely worn dentition. Composite resin veneers with favorable wear properties and esthetics are useful materials for restoring occlusions for overlay removable partial dentures. PMID- 1860122 TI - Restoring the severely compromised molar through adhesive bonding of amalgam to dentin. AB - Resin adhesive systems capable of bonding conventional amalgam to dentin, enamel, and cast restorations are now available. This article describes a case in which bonded amalgam was used to create a "vital core," permitting preservation of vitality during restoration of a molar where deep caries had encroached on the pulp. Without use of adhesive resin, the restoration would have required devitalization of the tooth, endodontic therapy, and fabrication of a crown retained by a post and core. PMID- 1860123 TI - Theme 3: Mainframing dentistry. Article 2: Biodiagnostic branching model systems (BBMS). PMID- 1860125 TI - The ADA's first female president: an Alaskan pioneer committed to service. PMID- 1860124 TI - Salivary gland cysts of the oral cavity: clinical observation and surgical management. AB - Mucoceles are common cystic lesions of the oral mucosa. Extravasation mucoceles are mainly found in the lower lip of young patients, whereas retention mucoceles are usually located in the cheek or palate of older patients. The disparate site and age incidences of extravasation and retention mucoceles suggest that these two types are not related and have different pathogenesis. Treatment modalities for mucoceles are reviewed, with special attention to the cryosurgical technique for the treatment of oral ranulas. PMID- 1860126 TI - Overdentures in partial anodontia: simple solutions for complex problems. AB - Congenital defects in children and adolescents can present complex and challenging dental problems, including arch discrepancies, palatal defects, and malposed or otherwise disrupted dentition. Traditional treatment is often time consuming, expensive, and in extensive defects, frequently compromised at best. The overdenture prosthesis, often overlooked, is a relatively simple and expedient solution to many of these severe problems, and the prosthetic techniques are familiar and readily employed by dentists without specialized training. This article reviews the general principles employed in these techniques and offers examples of successful treatment for several of the more commonly occurring congenital dental defects. PMID- 1860127 TI - Porcelain laminate veneers--to prepare or not to prepare? PMID- 1860128 TI - The safety and efficacy of tooth bleaching: a review of the literature 1988-1990. AB - Two hundred fifty-six major medical and dental journals were searched, and a comprehensive study was completed on the chemistry of hydrogen peroxide and carbamide peroxide. The results indicate that safety and efficacy of hydrogen peroxide is well established, while carbamide peroxide is much more complicated and no long-term safety studies are available for tooth bleaching using carbamide peroxide. PMID- 1860129 TI - Anticardiolipin antibodies in cluster headache. AB - Antiphospholipid antibodies have occasionally been observed in migraine patients, but a recent study of a large series suggested the association was with other concurrent conditions, not specifically with migraine. We wondered about an association with other vascular headaches and measured anticardiolipin antibody levels in 20 cluster headache patients during the cluster period (three during an acute attack). Platelet counts were normal and VDRL negative in all patients. No elevated anticardiolipin antibody levels were found. There appears to be no important association between the presence of anticardiolipin antibodies and cluster headache, and we argue that there is no further rationale for seeking one. PMID- 1860130 TI - Blood flow velocity changes in migraine attacks--a transcranial Doppler study. AB - A pulsed Doppler device was used to measure blood flow velocities in the common carotid artery, the extracranial part of the internal carotid artery, the external carotid artery, the middle cerebral artery, and the anterior cerebral artery in 31 migraineurs without aura (n = 27) and with aura (n = 4), both during and outside an attack. The aims were to compare blood flow velocity during and between migraine attacks and to study asymmetries of the blood flow velocity. Compared with blood flow velocity values obtained in the attack-free interval, blood flow velocity was lower during attacks without aura in both common carotid arteries, but not in the other extra- and intracranial vessels which were examined. However, during attacks of migraine with aura, blood flow velocity tended to be lower in all examined vessels. There were no asymmetries of the blood flow velocity. We suggest that during migraine attacks without aura there is a dissociation in blood flow regulation in the common carotid and middle cerebral arteries. PMID- 1860131 TI - EMG analysis of the late exteroceptive suppression period of temporal muscle activity in episodic and chronic tension-type headaches. AB - EMG analysis of the late exteroceptive suppression period of the temporal muscle activity is discussed as comparative methodology in the assessment of patients suffering from chronic tension-type headache and from migraineurs. After electrical perioral trigeminal nerve stimulation during maximum voluntary jaw occlusion, early (ES1) and late (ES2) exteroceptive suppression periods can be registered above the temples using surface EMG recordings. In patients suffering from chronic tension-type headache the duration of the late suppression period is shortened (p less than 0.001) compared to migraineurs or controls. However, patients suffering from episodic tension-type headache display late suppression periods of temporal muscle activity of differing lengths. PMID- 1860132 TI - Effectiveness of oral diclofenac in the acute treatment of common migraine attacks: a double-blind study versus placebo. AB - In a multicentre double-blind cross-over trial, oral diclofenac at a dose of 50 mg to 100 mg was compared to placebo in the acute treatment of migraine attacks. A hundred and seven patients suffering from migraine without aura were included, and 91 were analysed for efficacy; they had to treat four successive attacks--two with diclofenac and two with placebo. Diclofenac was significantly more effective than placebo (p less than 0.05) on the main judgement parameter, which was the number of attacks aborted within 2 h of drug intake, as well as on the following secondary parameters: the necessity for an escape medication and the evaluation of global efficacy. Diclofenac was well tolerated. This trial demonstrates the efficacy of diclofenac in the acute treatment of migraine attacks. It confirms the good clinical relevance of the main judgement parameter chosen, which is the one recommended by the International Headache Society, but appears to be a severe one in terms of successes. PMID- 1860133 TI - Magnetic resonance imaging of the brain in patients with migraine. AB - Magnetic resonance imaging (MRI) was studied in 91 patients with migraine and in 98 controls. Risk factors known to cause MRI lesions were carefully examined. In 36 patients with migraine (39.6%), small foci of high intensity on T2-weighted and proton-density-weighted images were seen in the white matter. Of patients with migraine who were less than 40 years old and without any risk factor, 29.4% showed lesions on MRI; this was significantly higher than the 11.2% for the group of age-matched controls (n = 98). The lesions were distributed predominantly in the centrum semiovale and frontal white matter in young patients, but extended to the deeper white matter at the level of basal ganglia in the older age group. The side of the MRI lesions did not always correspond to the side of usual aura or headache. Migraine-related variables such as type of migraine, frequency, duration or intensity of headache or consumption of ergotamine showed no significant correlation with the incidence of MRI abnormalities. Our data indicated that migraine may be associated with early pathologic changes in the brain. PMID- 1860134 TI - Exteroceptive silent period of temporalis muscle in menstrual headaches. AB - The second exteroceptive silent period (ES2) of temporalis muscle was recorded on days 1 and 15 of the menstrual cycle in 17 women, 9 of whom suffered regularly from tension-type headaches during menstruation. Mean duration of temporalis ES2 was significantly shorter on day 1 of the cycle than on day 15. This difference was due to a marked menstrual reduction of ES2 in the headache subgroup. A positive correlation was found between ES2 durations and oestradiol/progesterone ratios. We hypothesize that the variations of ES2 during the ovarian cycle result from the modulatory effects of oestrogens on descending aminergic pathways that control excitability of inhibitory brainstem interneurons mediating exteroceptive suppression of jaw-closing motoneurons. PMID- 1860135 TI - Chocolate is a migraine-provoking agent. AB - Patients with migraine who believed that chocolate could provoke their attacks were challenged with either chocolate or a closely matching placebo. In a double blind parallel group study, chocolate ingestion was followed by a typical migraine episode in 5 out of 12 patients, while none of the 8 patients challenged with placebo had an attack (p = 0.051). The median time to the onset of the attack was 22 h. This brief study provides some objective evidence that chocolate is able to provoke a migraine attack in certain patients who believe themselves sensitive to it. PMID- 1860136 TI - Blood magnesium levels in migraine. AB - Serum and erythrocyte magnesium levels were screened between attacks in patients with migraine without aura (n = 38) and with aura (n = 6), and for comparison in a group of patients suffering from chronic tension-type headache (n = 25) as well as a group of neurological, non-headache patients (n = 19). Serum magnesium levels were not significantly different between the four groups of patients. In contrast, magnesium in erythrocytes was on average significantly reduced in patients with migraine without aura compared to the other groups. It is hypothesized that this reduction might be due to an abnormal regulation of intracellular magnesium possibly reflecting at the periphery changes observed in the brain of migraineurs. PMID- 1860137 TI - Medicaid: have we been asked to contribute too much? PMID- 1860138 TI - Managed care. PMID- 1860139 TI - Purchasing a practice: the young dentist. PMID- 1860140 TI - Change in the heterogeneous distribution of tubulin isotypes in mitotic microtubules of the sea urchin egg by treatment with microtubule depolymerizing or stabilizing drugs. AB - In the mitotic sea urchin egg, the spindle microtubules were composed of different tubulin isotypes from those of astral microtubules using monoclonal antibodies [Oka et al. (1990) Cell Motil. Cytoskeleton, 16, 239-250]. Three of the antibodies, D2D6, DM1B, and YL1/2, were specific for spindle microtubules, astral microtubules and reactive with both microtubules, respectively. The mitotic sea urchin egg was treated with microtubule depolymerizing (colcemid and nocodazole) and stabilizing (hexylene glycol) drugs and change in the heterogeneous distribution of the tubulin isotypes was investigated by the immunofluorescence procedure using these three monoclonal anti-tubulin antibodies. We observed that: (1) the microtubule depolymerizing drugs caused quick depolymerization of most mitotic microtubules, and a small number of spindle microtubules remaining were stained with all three antibodies; (2) hexylene glycol induced many microtubules in the mitotic apparatus, which was stained with D2D6 but was not stained with DM1B; (3) hexylene glycol also induced a great number of miniasters in the cytoplasm, and they were stained with three antibodies. These results suggest that these drugs altered the distribution of tubulin isotypes in the mitotic microtubules during depolymerization or polymerization within a short time. PMID- 1860141 TI - Expression of chicken integrin beta 1 subunit in rat PC12 cells. AB - We transfected rat pheochromocytoma (PC12) cells with a cDNA encoding chicken integrin beta 1 subunit. The chicken integrin beta 1 subunit produced in stable transfectants associated with two major alpha subunits of rat integrins to form interspecific chimeric receptors. These receptors mediated cell spreading and initial neurite outgrowth on laminin as did corresponding endogenous integrins, although they were slightly less effective in inducing cell adhesion to laminin. These results indicate that chicken integrin beta 1 may functionally substitute for beta 1 subunit of rat integrins in PC12 cells. Apparently, the structure of the integrin beta 1 subunit is highly conserved in the evolution of these species. PMID- 1860142 TI - Immunoelectron microscopic detection of band 3 protein during erythroid cell differentiation by a monoclonal antibody. AB - We created a monoclonal antibody, designated EB1 (IgM, kappa), that reacts with erythroblasts by fusion of P3-X63-Ag8.653 with splenocytes of rats immunized with erythroblastic islands isolated from mice spleens. Western blotting revealed that EB1 reacted with the band 3 protein of the erythrocytic membrane. It stained erythrocytes and erythroblasts, forming clusters in the bone marrow, splenic red pulp, and fetal liver, but did not stain other tissues in the cryostat sections. The EB1 antigen was detected during dimethyl sulfoxide-induced differentiation of murine erythroleukemia cells. Immunoelectron microscopy revealed that the EB1 antigen was expressed from the basophilic erythroblasts during normal erythroid differentiation. Preferential segregation of the EB1 antigen on the cell membrane of the nucleating erythroblasts was not observed. These results suggest that EB1 is specific for erythrocyte band 3 protein and may be useful for studying erythroid cell differentiation. PMID- 1860143 TI - An immunoelectron microscopic comparison of desmosomal constituents and hemidesmosomal ones originating from the same tissue of the same animal. AB - The molecular constituents of desmosomes and hemidesmosomes were compared by examining bovine muzzle epidermis under immunoelectron microscopy using a postembedding method, first with antibodies prepared to four desmosomal antigens (DP1/2, DP3, DG1, DG2/3), followed by protein A-gold (PAG) complexes. The four antibodies showed almost negative labeling at hemidesmosomes as compared with the labeling observed at the desmosomes in the same tissue. By counting the number of PAG particles/200 millimicrons at hemidesmosomes and desmosomes, the above qualitative observation was confirmed quantitatively. These results support a new concept which has recently been proposed by several researchers that hemidesmosomes and desmosomes are immunochemically distinct. PMID- 1860144 TI - The reporting and management of adverse reactions to bacillus Calmette-Guerin (BCG) vaccination. PMID- 1860145 TI - Laboratory evidence of human viral and selected non-viral infections in Canada- 1990. PMID- 1860146 TI - Viability of adult Onchocerca volvulus after six 2-weekly doses of ivermectin. AB - Ivermectin is a safe, effective microfilaricide and microfilarial suppressant for Onchocerca volvulus; but in single doses of 100-200 micrograms/kg body weight it has no macrofilaricidal action. The present trial aimed to determine whether 6 doses of 100 micrograms/kg ivermectin, given at 2-week intervals, would kill the adult worms. Eighty-two nodules from 28 otherwise healthy adult male Liberian patients treated with this ivermectin schedule, and 102 nodules from a similar group of 25 control patients, were removed four months after the last dose of ivermectin. They were coded and assessed in a masked fashion either by routine histology or by examination of whole worms extracted from the nodules after collagenase digestion. The drug had no visible effect on adult male worms. More adult female worms were assessed as moribund or dead in the ivermectin-treated group than in the control group (for the collagenase digests P = 0.09; for the histological assessment P = 0.47). The data suggest that repeated dosage with ivermectin may lead to a slow attrition of some female worms and this possibility should be investigated in patients receiving regular doses every 3, 6 or 12 months as part of onchocerciasis control programmes. PMID- 1860147 TI - The risk and dynamics of onchocerciasis recrudescence after cessation of vector control. AB - Using a computer simulation study, we have investigated the risk and dynamics of onchocerciasis recrudescence after stopping vector control, in order to provide guidelines for operational decision-making in the Onchocerciasis Control Programme in West Africa (OCP). For this purpose, we used the microsimulation model ONCHOSIM to predict for periods of 9-15 years of vector control the ensuing risk and dynamics of recrudescence in an onchocerciasis focus. The model was quantified and validated using OCP evaluation and field research data. A range of plausible values was determined for important confounding parameters, i.e., vector biting rate, variation in exposure between individuals, parasite life span, and the relation between skin microfilarial load and vector infection. Different model quantifications were used in order to take account of the possible confounding effect of these parameters on the prediction of recrudescence. In the absence of immigration of infected humans or invasion by infected flies, the model predicts that 14 years of full-scale vector control are required to reduce the risk of recrudescence to less than 1%. The risk depends, in particular, on the vector biting rate, and this has implications for the planning of post-larviciding surveillance. Recrudescence will be a relatively slow process, and its rate will depend on the duration of vector control. Even if vector control were stopped too early, i.e., after 12-13 years in a highly endemic area, it would take more than 20 years before the intensity of infection in the community would reach levels of public health importance. PMID- 1860148 TI - Pharmacokinetics and pharmacodynamics of mefloquine in Thai patients with acute falciparum malaria. AB - A double-blind randomized comparative study of the pharmacokinetics and pharmacodynamics of a single oral dose of 750 mg or 1250 mg of mefloquine was carried out on 20 Thai male patients with acute uncomplicated falciparum malaria. In the 750-mg group, one patient exhibited an RII response, while the others responded to the treatment with a mean fever clearance time of 50.2 +/- 28.2 hours and a mean parasite clearance time of 70.2 +/- 17.3 hours. The main adverse effects were dizziness, nausea, vomiting, abdominal pain, and diarrhoea. Electrocardiogram monitoring detected sinus bradycardia in three patients and sinus arrhythmia in three others. In the 1250-mg group, one patient exhibited an RII response, while the others responded to the treatment with a mean fever clearance time of 43.4 +/- 36.6 hours and a mean parasite clearance time of 73.4 +/- 25.2 hours. However, during the follow-up period, two patients recrudesced on day 23 and on day 31 (RI response). Dizziness, nausea, vomiting, abdominal pain, and diarrhoea were the major adverse effects, with dizziness being more frequent compared with the 750-mg group. Sinus bradycardia occurred in four patients and sinus arrhythmia in four others. The pharmacokinetics of the two regimens were similar, with the absorption of mefloquine increasing linearly with the dose; however, vomiting within an hour of taking the drug reduced the whole blood mefloquine concentrations. The results do not indicate that there is any advantage in using a single dose of 1250 mg of mefloquine rather than 750 mg. PMID- 1860149 TI - Measles epidemic in Harare, Zimbabwe, despite high measles immunization coverage rates. AB - Despite rapidly increasing measles immunization coverage in Harare city, measles remains endemic, and regular outbreaks occur. The most recent occurred in 1988, when the measles immunization coverage was 83%. We have carried out a retrospective study of the clinical and epidemiological features of this outbreak to assess whether the present immunization policy needs to be changed. Of 4357 cases of measles seen at primary health care centres and hospitals in Harare during the outbreak, 1399 (32%) were severe or involved complications that required hospital admission. The peak incidence occurred among under-2-year-olds, followed by that among 5-7-year-olds. Poor nutritional status was significantly more frequent among children who were hospitalized and among those who died. A total of 59% of all cases aged 9-59 months had documented evidence of measles immunization. The most frequent complications, which occurred most often among under-5-year-olds, were diarrhoea with dehydration, pneumonia, laryngotracheobronchitis, and convulsions, which together affected 56% of hospitalized cases. The hospital case fatality rate was low (1.43%). In Harare, measles transmission remains a problem, despite high measles immunization coverage rates; the failure rate for the standard Schwarz measles vaccine also appears to be high. There is a need to reduce the number of measles cases among under-9-month-olds and young children. Further studies into alternative measles vaccines and schedules are required. PMID- 1860150 TI - Lack of efficacy of the standard potency Edmonston-Zagreb live, attenuated measles vaccine in African infants. AB - The efficacy of standard potency Edmonston-Zagreb (E-Z) measles vaccine was tested in a randomized trial of Black infants in a rural area of South Africa where a measles epidemic was occurring. The following immunization schedules were used: 48 infants aged 4-8.5 months who received 3.9 log 50 infectious units of E Z vaccine (group A); 48 infants aged 4-8.5 months who received 3.28 log 50 infectious units of Schwarz vaccine (group B); and 28 infants aged greater than 9 months who received 3.28 log 50 infectious units of Schwarz vaccine and served as controls (group C). For infants aged less than 23 weeks who were given either the E-Z or Schwarz vaccine, the number of seropositives was low (28%), irrespective of the pre-vaccination level of measles antibody. There was a higher number of seropositives (68%) among those in the age range greater than 23 weeks to less than 36 weeks who received the E-Z vaccine rather than the Schwarz vaccine (36%). When administered to children aged greater than 36 weeks, the Schwarz vaccine produced a satisfactory, though suboptimal response rate (61%). There was no correlation between seropositivity and pre-vaccination measles antibody status. Use of the standard dose of E-Z vaccine may have been one of the factors for this poor response, and this supports the WHO recommendation that titres higher than the standard potency vaccine are needed if 6-month-old infants are to be successfully immunized against measles. PMID- 1860151 TI - Oral rehydration therapy: a community trial comparing the acceptability of homemade sucrose and cereal-based solutions. AB - Sugar-based oral rehydration therapy (ORT) for diarrhoea is promoted in many countries of the world. One programme in Bangladesh has instructed more than 13 million mothers in the preparation of a sugar-salt solution in the home; despite very high rates of correct mixing and knowledge, subsequent application was found in only some 20% of all diarrhoea episodes. Since rice is far more available in rural homes (95%) than any type of sugar (30%) and rice gruel is a widely accepted food during illness, a field trial was conducted in three areas (total population, 68,345) to compare the acceptability and use of rice-based ORT with that of sugar-based ORT. Although the mothers unanimously agreed that the rice based solutions "stopped" the diarrhoea more quickly, they used the sugar-based solutions twice as often (in 40% of severe watery episodes) as the rice-based solutions (in 18%), because the rice-ORT was much more time-consuming and difficult to prepare. The observed reduced utilization of home-made rice-ORT makes it a poor substitute for sugar-ORT at the community level in rural Bangladesh. PMID- 1860152 TI - Vitamin A deficiency and corneal ulceration in south-east Nepal: implications for preventing blindness in children. AB - A retrospective review of the outpatient records of 4601 children aged 0-10 years who had been seen between January 1986 and December 1988 at Lahan Eye Hospital, south-east Nepal, revealed that 15.4% had evidence of active or past xerophthalmia. Of 293 children with corneal xerosis or corneal ulcer, 49% had been examined in the 4-month period May-August. The peak age for active noncorneal xerophthalmia was 5 years and for active corneal xerophthalmia, 3 years. Previous population-based studies in Nepal have documented the presence of noncorneal xerophthalmia (Bitot's spots) in children. The present study confirms that vitamin A deficiency is a major cause of blindness and loss of vision among children in the eastern plains of Nepal. PMID- 1860154 TI - Neuropsychiatric aspects of HIV-1 infection: data collection instrument for a WHO cross-cultural study. PMID- 1860153 TI - Risk of transmission of AIDS and other blood-related diseases during routine malaria activities. PMID- 1860155 TI - A species/strain comparison of hepatic natural lymphocytotoxic activities in rats and mice. AB - The natural killer (NK) and natural cytotoxic (NC) cell activities in livers from certain rat and mouse strains were compared. This included the two rodent strains used in animal carcinogenicity bioassays, i.e. Fischer 344 and B6C3F1 mice. Sprague-Dawley and Fischer 344 rats exhibited high hepatic NK activity, which was greater than the levels seen in all of the five mouse strains studied. However, the hepatic NC activity in rats was comparable to the activities observed in C57BL and BALB/c mice. An inverse relationship was observed between the two tumoricidal activities in all but one of the mouse strains examined; that is (at 8 weeks of age), NK activity: C3H greater than B6C3F1 greater than CBA greater than BALB/c; NC activity: BALB/c much greater than CBA greater than B6C3F1 greater than C3H. The C57BL mouse strain was the only strain to express both activities at comparatively high levels. Female mice exhibited a similar profile of cytotoxic activities. Rats also possessed high activities of a presently ill defined tumoricidal activity, this being the spontaneous P815 mastocytoma killing by unstimulated effector cells, over an 18 h period. Both adherent and nonadherent effector cells from rat livers, but only the nonadherent cell population isolated from male mouse livers, exhibited this activity which may represent a distinct hepato-specific population of natural lymphocytotoxic effector cells. The tumoricidal activities in liver-derived cells were greater than those of effector cells isolated from the spleen. The differences in natural immunity reported in this study may be related to the varying background incidences of hepatic tumors, i.e. the mouse strains susceptible to high background incidences of liver tumors have relatively low natural immunity, whereas the two mouse strains resistant to hepatic tumors possess high levels of at least one hepatic NLC activity. Similarly, rats have relatively low hepatic tumor rates and high levels of hepatic natural immunity. PMID- 1860156 TI - Studies in gastric carcinogenesis. V. The effects of ascorbic acid on N-nitroso compound formation in human gastric juice in vivo and in vitro. AB - The concentrations of nitrite, thermo- and acetic acid-labile TEA-responsive compounds (TACs) and N-nitroso compounds (NOCs) as a group were measured in human gastric juice collected just before and 1, 2 and 4 h after oral ingestion of 1 g ascorbic acid (AA) or 200 mg sodium nitrate, separately or in combination. Individual responses of gastric [nitrite] following ingestion of AA alone varied widely, with both decreases and increases being observed, and showed no correlation with gastric pH. While a mixed response was also noted for [NOC] and [TAC], substantial decreases were observed in 5/6 individuals with initial [NOC] greater than 0.2 microM and 3/3 individuals with initial [TAC] greater than 0.2 microM, implying that (i) AA effectively inhibited gastric nitrosation and (ii) a basal amount of NOCs and TACs was present in gastric juice which could not be lowered by AA ingestion. Statistical analysis indicated that global mean values of gastric [NOC] were significantly reduced (P less than 0.02) 1-4 h after ingestion of AA. Ingestion of 200 mg sodium nitrate alone resulted in increases in gastric [NOC], which in some cases were very substantial. While nitrosation appeared lower following ingestion of the same dose of nitrate in combination with 1 g AA, the difference from the effects of nitrate alone was not statistically significant. In aqueous buffer, pH 2.5, and in the presence of 1 mM AA, 50 microM nitrite was consumed with a t1/2 of 50 min only if molecular oxygen had first been removed from the system. In the presence of oxygen, no consumption of nitrite could be detected in 50 min, reflecting nitrite recycling (oxidation of nitric oxide to higher oxides of nitrogen and hydrolysis back to nitrite). It is likely that nitrite recycling occurring after collection of gastric juice accounted for the inconsistent responses of gastric nitrite following ingestion of AA. Incubation of human gastric juice, pH 2.5, in vitro in the presence of 50 microM sodium nitrite for 60 min resulted in an increase of [NOC] and [TAC] from 0.10 to 0.70 and 1.10 microM respectively. Nitrosation was efficiently inhibited by AA, 2.27 mM AA resulting in 87 and 100% inhibition respectively. Removal of oxygen from the reaction mixture did not have any significant effect on the extent of nitrosation in the presence or absence of AA. PMID- 1860157 TI - Tumorigenesis by short-wave ultraviolet A: papillomas versus squamous cell carcinomas. AB - The tumorigenic properties of UBV radiation (wavelengths 280-315 nm) are well established, in contrast to those of UVA radiation (315-380 nm). Very little information is available on the short UVA wavelengths (315-340 nm). To expand our knowledge on UVA tumorigenesis we investigated the development of skin tumours in albino hairless mice (SKH-hr1) exposed to custom-built experimental fluorescent tubes (EFL330) with spectral output centred around 330 nm. Two groups received continued daily exposures: one 56 kJ/m2 and the other 20 kJ/m2 per day. The third group was exposed to yellow fluorescent light devoid of UV, and served as a control. Each group consisted of 24 mice. Most of the mice in the high-dose group developed tumours; after 431 days 50% were tumour bearing. Two main types of tumours were observed: papillomas (Pap) and squamous cell carcinomas (SCC). In the low dose group only three mice attracted one papilloma each. No tumours were seen in the control group. Results show that the short-wave as well as the long wave UVA contributes to carcinogenicity; the short wavelengths being approximately 5 times more efficient. The kinetics of tumour development under UVA exposure appeared to be different from that under UVB exposure. If, however, we exclude papillomas from our analysis, development is very much the same as with UVB irradiation, which yields predominantly SCC. PMID- 1860158 TI - The role of hyperplastic nodules in dichloroacetic acid-induced hepatocarcinogenesis in B6C3F1 male mice. AB - Dichloroacetic acid (DCA) has recently been shown to increase significantly the incidence of hepatic adenomas (HAs) and hepatocarcinomas (HCs) in male B6C3F1 mice. Although little is known about the mechanism of DCA carcinogenesis, chronic ingestion of the compound in drinking water induces primarily hyperplastic nodules (HNs) prior to the appearance of HAs and HCs. Given the putative preneoplastic potential of the HNs, we undertook this study to determine the role of the HNs in the progression of DCA-induced hepatocarcinogenesis. This role was assessed by detecting the expression of five different tumor markers: p21 ras, p39 c-jun, phosphotyrosine, tumor-associated aldehyde dehydrogenase and alpha fetoprotein, all known from previous studies to be expressed more often in neoplastic liver lesions than in normal liver. Tumor marker expression was detected by immunohistochemical methods using formalin-fixed, paraffin-embedded sections of normal B6C3F1 mouse liver, and DCA-induced HNs, HAs and HCs. The results demonstrated that, except for the c-jun marker, HNs expressed the markers significantly less often than either HAs or HCs. Equal expression of c-jun occurred in any of the three lesion types. Although these results could be used to argue that no relationship existed between HNs and later-appearing HAs and HCs, those HNs that were marker positive contained small nests of marker-positive hepatocytes among a field of normally appearing unstained hepatocytes. No similar nests of marker-positive cells were detected in any area of normal liver outside the HNs. Also very few altered hepatic foci (AF) were detected with these markers or with hematoxylin and eosin, or with histochemical stains for ATPase or glucose 6-phosphatase deficiencies. These results suggested that these nests within some HNs were areas of transformed, or neoplastic hepatocytes. Phenotypic heterogeneity analysis, in which the number of tumor markers co-expressed by any given lesion was examined, confirmed a significantly greater percentage of HAs and HCs expressing multiple markers than HNs. Those HNs that expressed multiple markers, however, expressed at the same frequency as HAs and HCs and the expression was confined to the same nests of cells. Taken together, these data suggest that these nests of marker-positive cells within the HNs were neoplastic and could develop into later-appearing HAs and/or HCs. The absence of marker expression in normal liver and limited expression in the few AF indicates that the HNs may be the only significant preneoplastic lesion in DCA-induced hepatocarcinogenesis. PMID- 1860159 TI - O(6)-methylguanine-DNA methyltransferase and uracil DNA glycosylase in human broncho-alveolar lavage cells and peripheral blood mononuclear cells from tobacco smokers and non-smokers. AB - Because interindividual variations in the activities of DNA repair enzymes may be a risk factor in the pathogenesis of lung diseases, O(6)-methylguanine-DNA methyltransferase (O(6)-MT) and uracil DNA glycosylase (UDG) were measured in broncho-alveolar lavage cell (BALC) and peripheral blood mononuclear cell (PBM) samples from 57 healthy volunteers (25 smokers and 32 non-smokers). According to cotinine determination in 39 cases where serum for this was available, 38% of the self-acclaimed non-smokers had greater than 10 ng/ml of cotinine in their serum. Whether grouped into smokers and non-smokers according to clinical history or by serum cotinine, there were no statistically significant differences between these groups in O(6)-MT or UDG in either of the cell types. However, a tendency towards lower values in smokers was seen. The highest intraindividual variation in O(6) MT activity was 7-fold, while the highest interindividual variation reached 18 fold. For UDG, the respective values were 24- and 307-fold. Although the distribution of O(6)-MT in BALC was different from that in PBM, the data are consistent with unimodality in both of the cell types. These findings suggest that exposure to cigarette smoke is not entirely responsible for the wide interindividual variation in O(6)-MT and UDG DNA repair activities. PMID- 1860160 TI - Endogenous N-nitrosation in man assessed by measurement of apparent total N nitroso compounds in faeces. AB - The faecal concentration of substances responding to the chemical test for N nitroso compounds (apparent total N-nitroso compounds, ATNC) was investigated in human subjects consuming their normal free-choice diet. Concentrations ranged from 40 to 590 micrograms (N-NO)/kg faeces. To ascertain the likely relative contributions of endogenous ATNC formation and preformed, dietary ATNC, the subjects consumed a diet low in nitrate and ATNC for 8 days. At the end of this period, ATNC had decreased substantially with concentrations ranging from below the 40 micrograms (N-NO)/kg detection limit up to 143 micrograms (N-NO)/kg, mean 82 micrograms (N-NO)/kg. On supplementing this diet with 300 mg nitrate/day, faecal ATNC levels increased markedly. On the third day of this regime, values were in the range 73-714 micrograms (N-NO)/kg with a mean of 307 micrograms (N NO)/kg. The results, together with the known limited occurrence of ATNC in the majority of foodstuffs so far tested, generally non-detectable or less than 100 micrograms (N-NO)/kg, suggest that endogenous formation via species derived from dietary nitrate is likely to be an important source of ATNC in human faeces. PMID- 1860161 TI - The differential clastogenicity of Solvent Yellow 14 and FD & C Yellow No. 6 in vivo in the rodent micronucleus test (observations on species and tissue specificity). AB - Solvent Yellow 14 is carcinogenic in rats, inducing neoplastic nodules of the liver, but is non-carcinogenic in mice. The present paper shows that Solvent Yellow 14 induces micronuclei in the bone marrow of rats after a single oral dose of 250 mg/kg and above. In mice, however, there was no increased incidence of micronuclei after single oral doses of up to 2000 mg/kg Solvent Yellow 14, thus reflecting the species specific carcinogenic effect of the compound. The structurally related azo dye FD & C Yellow No. 6 is noncarcinogenic to rats and mice and gave a negative result in both rat and mouse bone marrow micronucleus tests after a single oral dose of up to 2000 mg/kg. The rat bone marrow micronucleus test is therefore capable of discrimination between the carcinogenic and the non-carcinogenic azo dye. A negative result was obtained for Solvent Yellow 14 in an in vivo liver unscheduled DNA synthesis assay after oral doses up to 1000 mg/kg. This result demonstrates the inability of the two in vivo assays used to predict target organ specificity seen in the cancer bioassay. PMID- 1860162 TI - Evaluation of the newborn mouse model for chemical tumorigenesis. AB - A total of 45 chemicals, including two aromatic hydrocarbons, five aromatic amines, three azo dyes, ten nitroso compounds, three steroids, four tryptophan metabolites and their related compounds, four naturally occurring substances, four pyrolysates of amino acids and ten miscellaneous compounds, were tested for newborn mouse tumorigenesis assay (NMTA). The results of the NMTA were compared with data from 'Survey of Compounds Which Have Been Tested for Carcinogenic Activity', NIH, NCI, USA (SCWHBTCA), and also with data from the IARC Monographs (Vols 1-41), Lyon, France (IARC). Of the 45 chemicals tested by the NMTA, 28 chemicals showed positive results in the NMTA, and the remaining 17 chemicals were found to be negative for tumor development. The correlation of the results between the NMTA and the mouse and/or rat carcinogenesis test starting at young adult age reported in the SCWHBTCA and in the IARC were compared with 37 chemicals tested; the remaining eight chemicals were found only in our NMTA results. It can be concluded that 31 out of 37 chemicals (83.8%) tested by the NMTA showed similar carcinogenic or non-carcinogenic results obtained in either adult mouse and/or rat carcinogenesis tests. The remaining six chemicals showed contradictory results between the NMTA and either adult mouse and/or rat carcinogenesis tests. Those six chemicals were N-hydroxy-4-acetylaminobiphenyl, estradiol, 3-hydroxyanthranilic acid, 3-hydroxy-L-kynurenine, isonicotinic acid hydrazide and phenobarbital. Among the 37 chemicals, 34 were comparable with the results of the adult mouse carcinogenesis test and those of the NMTA. Twenty-nine out of 34 chemicals (85.3%) showed similar results to the adult mouse carcinogenesis test. Contradictory results were obtained with the following five chemicals: N-hydroxy-acetylaminobiphenyl, 3-hydroxy-anthranilic acid, 3-hydroxy-L kynurenine, isonicotinic acid hydrazide and phenobarbital. There were 35 chemicals which were comparable with the results of the adult rat carcinogenesis test, and 32 chemicals showed the same results as the NMTA (91.4%). Dissimilar results were obtained with the following three chemicals: estradiol, 3-hydroxy anthranilic acid and phenobarbital. Based on the results presented in this report, it is reasonable to conclude that the NMTA is one of the most useful and reliable methods for detecting tumorigenic or non-tumorigenic chemicals, when a small amount of chemical is available for rodent carcinogenesis test and the duration of the study is limited to 1 year. PMID- 1860163 TI - Measurement by 32P-postlabelling of 7-methylguanine levels in white blood cell DNA of healthy individuals and cancer patients treated with dacarbazine and procarbazine. Human data and method development for 7-alkylguanines. AB - A 32P-postlabelling method was developed to measure 7-methylguanine in human DNA. DNA was digested to nucleotides and 7-methyl-2'-deoxyguanosine-3'-monophosphate (7-me-dGMP) was isolated from normal nucleotides using strong anion-exchange column chromatography. Overall the method gave 35-45% yield as measured with DNA methylated with tritiated dimethyl sulfate. Total white blood cell DNA from healthy non-smokers (n = 17) contained from 2.5 7-methylguanine residues/10(7) nucleotides, corrected for the losses in preparation. Among four patients sampled immediately after a total dose of 1050-2800 mg of dacarbazine or procarbazine, the mean adduct level was 57 7-methylguanine residues/10(7) nucleotides. As further method development, we also investigated the phosphorylation reaction by T4 polynucleotide kinase using dinucleotides containing 7-methylguanine and corresponding imidazole ring-opened products as substrates. We found that imidazole ring-opened dTpdG-Me is resistant to digestion with deoxyribonuclease I, snake venom phosphodiesterase and prostatic acid phosphatase. It is quantitatively phosphorylated at femtomolar levels. This method is shown to be suitable for the detection of 7-methylguanine in DNA, and is suggested to be the approach most suited to postlabelling large and labile 7-alkylguanines in DNA. PMID- 1860164 TI - Reversibility of adenomatous hyperplasia in the gastric stump after diversion of bile reflux in rats. AB - Morphological and phenotypical patterns of proliferative epithelial lesions induced in the gastric stump mucosa by duodenal content reflux after Billroth II partial gastrectomy (BII) were evaluated in rats. Control animals were either sham-operated or submitted at different times after BII to Roux-en-Y (RY) surgical procedure which prevents duodenal reflux. The lesions were analysed using routine haematoxylin and eosin staining, immunohistochemical staining for pepsinogen isoenzyme 1 and histochemical procedures for mucins (paradoxical Concanavalin A, galactose oxidase Schiff and sialidase galactose oxidase Schiff reactions). Mucosal hyperplasia (H) was observed in the group submitted to BII procedure 6 weeks after surgery. Adenomatous hyperplasia (AH) also appeared 6 weeks after induction of the reflux and its incidence and size increased until the 54th week of the experiment. RY procedure performed in the normal animals at the beginning of the experiment or at the 24th week after BII gastrectomy led to a significantly lower incidence of AH which was related to the moment of surgery. Most of H was due to pyloric mucosal hyperplasia. AH consisted mainly of gastric type glands but in some animals glands of the intestinal type were present probably originating from the intestinal mucosa. Six mucinous adenocarcinomas were observed, all of them of intestinal type. This study demonstrates that AH induced by BII procedure is a reversible lesion and that the anomalous epithelial proliferation in the stoma may lead to adenocarcinomas. PMID- 1860165 TI - Fluorescence detection of benzo[a]pyrene--DNA adducts in human lung. AB - Improved techniques are described for the specific identification of benzo[a]pyrene-diolepoxide (BPDE)--DNA adducts in human tissues. Immunoaffinity chromatography, synchronous fluorescence spectroscopy and second-derivative synchronous fluorescence spectroscopy have previously been used to detect BPDE DNA adducts in human placenta. Here we report how these methods, together with HPLC and the generation of complete fluorescence excitation--emission matrices, have been used to identify unequivocally BPDE-DNA adducts in samples of human lung. BPDE nucleotide adducts were isolated with immunoaffinity chromatography columns bearing antibodies raised against the (+/-)anti-7,8-diol-9,10-epoxide deoxyguanosine adduct of benzo[a]pyrene. These adducts were hydrolyzed to tetrahydrotetrols and the hydrolysis products subjected to HPLC. The major product isolated by HPLC, benzo[a]-pyrene-7,10/8,9-tetrahydrotetrol, was determined by fluorescence spectroscopy. Using this method, levels of BPDE-DNA adducts in the range of 1-40 in 10(8) nucleotides were measured in 6 out of 25 samples, with a lower detection limit of one adduct in 10(8) nucleotides. The data may also indicate that adduct levels show regional variation in different parts of the same lung. PMID- 1860166 TI - Resistance of female Fischer-344 rats to the hepatonecrogenic and hepatocarcinogenic actions of a choline-devoid diet. AB - A series of experiments was performed to investigate the response of female Fischer-344 rats to a choline-devoid (CD) diet. In contrast to findings previously made in male Fischer-344 rats, hepatocellular carcinomas did not develop in females chronically fed the diet. Their liver actually showed only minimal histopathological changes. For these reasons, the steatogenic and hepatonecrogenic actions of a CD diet were compared in male and female Fischer 344 rats. Young adult females were found to be largely resistant to both. The results were taken as further evidence of the primary and essential role played by an enhanced cell turnover in the pathogenesis of the carcinomas induced in male Fischer-344 rats by this non-chemical, nutritional model of hepatocarcinogenesis. A high incidence of preneoplastic and benign lesions developed in breast, pancreas or stomach of females chronically fed the CD diet. However, a similar spectrum and high incidence of lesions was observed in control rats fed a choline-supplemented diet. These findings were attributed to an enhanced occurrence of spontaneous lesions, most likely due to the high fat content (15%) of the two diets used. PMID- 1860167 TI - Distribution of acetyltransferase activities in the intestines of rapid and slow acetylator rabbits. AB - Epidemiological studies have shown that there is a significantly greater proportion of the rapid acetylator phenotype in patients with colorectal tumors than in controls; phenotype-related differences in bioactivation of dietary or environmental amines in the intestinal epithelium have been suggested as a mechanism for this effect. In the present study, we have used hepatic and intestinal cytosols to compare N-acetyltransferase (NAT1 and NAT2), O acetyltransferase (OAT) and arylhydroxamic acid N,O-acyltransferase (AHAT) distribution in rapid and slow acetylator rabbits. The ratio (rapid/slow) for p aminobenzoic acid acetylation (a selective substrate for NAT1) was 6 in liver, 1.7-2 in small intestine and 1.3-1.5 in large intestine while the ratio of sulfamethazine acetylation (a selective substrate for NAT2) was 150 in liver, 16 22 in small intestine and 1.8-2.5 in large intestine. The ratios (rapid/slow) for DNA binding of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl and N-hydroxy-4 aminobiphenyl (primarily substrates for OAT) were 82-84 in liver, 13-20 in small intestine and 3.8-5.3 in large intestine and for DNA binding of N-hydroxy-2 acetylamidofluorene (a substrate for AHAT), the ratio was 432 in liver, 32-161 in small intestine and 8.8-13.5 in large intestine. The data show also that NAT1 activity is uniformly distributed along the intestinal tract whereas NAT2 activity is highest in the small intestine. In addition, hepatic and intestinal OAT and AHAT but not NAT1 activities in the rabbit intestine are similarly distributed to activities for NAT2, suggesting that NAT2, OAT and AHAT activities are properties of a single protein in the rapid acetylator phenotype. Moreover, OAT and AHAT activities were much higher in tissues from the rapid than the slow phenotype. The data support the hypothesis that phenotype-dependent metabolic activation of N-OH heterocyclic or aromatic amines to reactive acetoxy metabolites may be involved in the etiology of colorectal cancer. PMID- 1860168 TI - Glutathione transferase isoenzymes in normal and neoplastic human kidney tissue. AB - Glutathione transferase (GST) activity in the cytosolic fractions of renal cortex tumour was found to be significantly lower (215 +/- 156 mU/mg) than that present in the corresponding non-tumour (466 +/- 278 mU/mg) tissues. Using the immunoblotting technique, glutathione transferase isoenzymes expression in both tumour and non-tumour kidney was investigated. Alpha and pi class glutathione transferases were the most abundant enzymes in non-tumour kidney and were expressed by all samples investigated. Immunofluorescence analysis indicated that the pi class enzymes are localized mainly in the distal convoluted tubules, whereas alpha class enzymes are localized in the proximal tubules. In the tumour moiety the alpha class GST appears to be absent or expressed at low level as compared with non-tumour samples. On the contrary, no significant differences in the expression of pi class GST were found in tumour as compared with non-tumour tissues. Mu class GST protein was detected in 12 of 26 samples tested. When present, mu class GST constitutes a few per cent of total GST protein. Immunofluorescence studies indicate that mu class GSTs are localized within the distal convoluted tubules. According to the electrophoretic mobility at least two different mu GST subunits (26.5 and 27.5 kd) were found. In one sample only the faster mu class GST subunit was present, two samples expressed both types of GST subunits, whereas nine samples expressed only the slower GST subunit. With the exception of one sample, a reduction of mu class GST expression was seen in tumour as compared with non-tumour tissues. The decrease of activity seen in the cytosolic fraction of tumour kidney must be ascribed mainly to a reduction or to a lack of expression of alpha class GST and to a lesser extent of mu class GST. PMID- 1860169 TI - Activation of c-K-ras is frequent in pancreatic carcinomas of Syrian hamsters, but is absent in pancreatic tumors of rats. AB - We have investigated the presence of mutations in ras genes at codons 12, 13 and 61 in chemically induced pancreatic tumors of rats and Syrian hamsters. Mutations were detected by means of allele-specific oligonucleotide hybridization to ras sequences amplified in vitro by the polymerase chain reaction. No mutations were observed in the c-K-ras gene or the c-H-ras gene of nine azaserine-induced adenomas and 15 carcinomas of the rat pancreas. This indicates that activated ras genes are not commonly involved in rat pancreatic cancer evolving from acinar cells. However, in 19 out of 20 ductular adenocarcinomas of hamster pancreas (95%), either codon 12 or 13 of the c-K-ras gene was mutated. This indicates that the activation of c-K-ras is a frequent event in the multistep process of pancreatic carcinogenesis induced by the alkylating carcinogen N-nitrosobis(2 oxopropyl)amine (BOP). The mutations of both codons were G----A transitions of the second base which is consistent with the type of mutation to be expected from DNA alkylation. Activation of the c-K-ras gene, therefore, may not only be a frequent but also an early event in hamster pancreas carcinogenesis. The frequent activation of the c-K-ras gene in both human and hamster pancreatic cancer emphasizes the relevance of BOP-induced pancreatic adenocarcinomas in Syrian hamsters as an experimental model system for studying human pancreatic cancer. PMID- 1860170 TI - Detection of acrolein and crotonaldehyde DNA adducts in cultured human cells and canine peripheral blood lymphocytes by 32P-postlabeling and nucleotide chromatography. AB - People are constantly being exposed to toxic and carcinogenic aldehydes. However, little is actually known about the mechanisms underlying the toxic and carcinogenic effects of these aldehydes on human cells. The DNA alkylating activities of two of the more toxic and environmentally prominent alpha,beta unsaturated aldehydes, acrolein and crotonaldehyde, have been studied utilizing 32P-postlabeling and nucleotide chromatographic techniques. Several putative adducts were observed in DNAs isolated from acrolein- and crotonaldehyde-treated human fibroblasts. One of these acrolein-DNA adducts was tentatively identified as the cyclic 1,N2-hydroxypropanodeoxyguanosine product, 3-(2'-deoxyribosyl) 5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2- a]purine-10-one, by co-chromatography with a chemical standard. The 1,N2-hydroxypropanodeoxyguanosine along with other possible adducts, was also found in DNA isolated from peripheral blood lymphocytes obtained from a dog 1 h after receiving a therapeutic dose of 6.6 mg/kg of cyclophosphamide. These results not only demonstrate the presence of acrolein and crotonaldehyde DNA adducts in treated human cells, but also suggest that these sensitive techniques may be useful to the study of the importance of acrolein to both the carcinogenic and antineoplastic activities of cyclophosphamide and other oxazaphosphorine mustards. PMID- 1860171 TI - A new colon and mammary carcinogen in cooked food, 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP). AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which is produced during cooking and is mutagenic to bacteria and cultured mammalian cells, was found to induce high incidences of colon and mammary carcinomas in F344 rats when administered at a concentration of 400 p.p.m. in the diet for 52 weeks. Since PhIP is the most abundant of the mutagenic heterocyclic amines in cooked meat and fish, the compound might be related to malignancies of the colon and breast in humans. PMID- 1860172 TI - 32P-postlabelling analysis and micronuclei induction in primary Chinese hamster lung cells exposed to tobacco particulate matter. AB - The genotoxicity of tobacco particulate matter (TPM) derived from a low-tar, low nicotine cigarette has been examined by measuring micronucleus induction in a primary pulmonary cell line, both in the absence and presence of an exogenous source of metabolic activation. In an attempt to correlate the cytogenetic damage observed with DNA adduct formation, DNA extracted from TPM-treated cells has been analysed with two different modifications of the 32P-postlabelling assay. The results from the 32P-postlabelling analysis taken together with the pattern of micronucleus induction provide strong evidence that bioreactivated aromatic carcinogens, such as benzo[a]pyrene, are unlikely to be responsible for the TPM induced cytogenetic damage observed in cultured mammalian cells. PMID- 1860173 TI - Protection against ultraviolet B radiation-induced photocarcinogenesis in hairless mice by green tea polyphenols. AB - Our recent studies have shown that polyphenols present in green tea (GTP) possess significant antigenotoxic activity and afford protection against polycyclic aromatic hydrocarbon-induced skin tumor initiation in mice. In this study we assessed the effect of oral feeding and topical application of GTP on ultraviolet B (UVB) radiation-induced skin carcinogenesis in female SKH-1 hairless mice. Chronic oral feeding of GTP (0.1%, w/v) in drinking water resulted in significantly (P less than 0.01) lower tumor yield (percent of animals with tumors and number of tumors per mouse) and extended TDT50 (P less than 0.05), as compared to animals receiving normal drinking water. Topical application of GTP before UVB irradiation also afforded protection against photocarcinogenesis; however, the protective response was lower than that observed by oral feeding of GTP in drinking water. These results, in conjunction with our prior publications, suggest that consumption of green tea may reduce the risk of some forms of human cancer induced by both physical and chemical environmental carcinogens. PMID- 1860175 TI - Calcium current depression in isolated human atrial myocytes after cessation of chronic treatment with calcium antagonists. AB - The present study investigates the possibility that the slow calcium current of human atrial cardiac cells is modified by chronic treatment (1-24 months) with calcium antagonists (nifedipine, nicardipine, or diltiazem) in a manner different from a simple drug-induced blocking effect. Data from treated patients were recorded approximately 30 hours after cessation of the treatment and were compared with those of nontreated patients. In the treated group, the action potential plateau of atrial fibers was always markedly and irreversibly depressed, and action potential duration measured at 50% repolarization was markedly shortened (81 +/- 12 msec, n = 13) compared with normal values (155 +/- 9 msec, n = 28). In isolated atrial cells, peak calcium current density at +10 mV in treated cells was more than three times as small as that in nontreated cells. Steady-state inactivation relations of calcium current as a function of membrane potential were not significantly different in treated and nontreated cells. In contrast, in treated and nontreated cells superfused with 10(-6) M nifedipine, the curves were markedly shifted toward negative potentials. Cell superfusion with 10(-6) M Bay K 8644 increased calcium current to a larger extent in nontreated cells (sixfold increase) than in treated cells (threefold increase), whereas a 23-fold increase was observed in nontreated cells in which the current had been previously depressed by superfusion with 10(-6) M nifedipine. In contrast to Bay K 8644, 10(-7) M isoproterenol and 10(-8) M angiotensin II increased the calcium current to the same extent in both treated and nontreated groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860174 TI - Restricted secretion of a T-lymphocyte chemotactic cytokine by serotonin stimulated cultured aortic endothelial cells. AB - The diversity of biologically active molecules produced by vascular endothelium suggests that the endothelial cell is an active participant in numerous physiological responses, including those of the immune system. In fact, the accumulation of T lymphocytes at extralymphatic inflammatory foci represents a series of interactions between lymphocytes and vascular endothelial cells. These interactions, however, may be modulated by other factors, such as vasoactive amines. In the current study, we report that serotonin-stimulated cultured bovine aortic endothelial cells (BAECs) secrete a T-lymphocyte chemotactic cytokine (endothelial cell-derived lymphocyte chemotactic activity [ED-LCA]). Supernatants from BAECs incubated with 10(-7)-10(-4) M serotonin (5-hydroxytryptamine [5-HT]) enhanced T-cell migration, which peaked at 10(-5) M 5-HT (235 +/- 18% control migration). ED-LCA was not stored in an active form in BAECs; its secretion occurred within 60 minutes of exposure to 5-HT and was blocked by two different 5 HT2 receptor antagonists. ED-LCA was not secreted after exposure of BAECs to histamine or angiotensin II, nor was it secreted by either 5-HT-stimulated bovine pulmonary arterial or human umbilical vein endothelial cells. Physicochemical characterization of ED-LCA demonstrated that it was a trypsin-sensitive protein with an apparent molecular mass of 13-15 kDa. Preparative isoelectric focusing demonstrated pIs of 6.0 and 7.5. When applied to a molecular sieve column, the chemotactic activity corresponding to these pIs eluted in the region of 13-15 kDa. Further investigation demonstrated that partially purified ED-LCA was specific for CD4+ and CD8+ T-lymphocyte subsets and did not enhance the migration of neutrophils or monocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860176 TI - Myocardial contractile actions of endothelin-1 in rat and rabbit papillary muscles. Role of endocardial endothelium. AB - The actions of endothelin on the contractile and twitch configuration characteristics of rat and rabbit papillary muscles were evaluated before and after endocardial endothelium removal. In rabbit papillary muscles, endothelin produced a dose-dependent (10(-11) to 10(-7) M) increase in tension (T) (from 2.7 +/- 0.2 to 8.9 +/- 0.7 g/mm2, p less than 0.01), dT/dt, and Vmax (from 1.14 +/- 0.03 to 3.0 +/- 0.13 Lmax/sec, p less than 0.01), a decrease in time to peak tension (from 251 +/- 9 to 216 +/- 7 msec, p less than 0.05), and an increase in time to half relaxation (from 168 +/- 9 to 293 +/- 14 msec, p less than 0.01). Increasing calcium concentration in the bath from 1.25 to 15 mM greatly attenuated these changes. In the presence of propranolol (10(-5) M), endothelin increased all indexes of contractility but to a lesser extent (T = 2.6 +/- 0.3 to 6.5 +/- 0.2 g/mm2, p less than 0.01; Vmax = 1.16 +/- 0.10 to 2.06 +/- 0.10 Lmax/sec, p less than 0.01). Myocardial catecholamine depletion with reserpine had effects similar to those of propranolol. The myocardial contractile and twitch configuration characteristics of endothelin were similar to those of phenylephrine (10(-4) M), a strong stimulator of the phosphatidylinositol pathway and a moderate beta-adrenergic stimulator. The effects of phenylephrine and endothelin were modified in a similar manner by propranolol (10(-5) M). The presence of nicardipine (3 X 10(-7) M) decreased the absolute increase in contractility caused by endothelin but did not alter the percent change or shift the dose-response curve of endothelin. The actions of endothelin in rat papillary muscles studied at physiological calcium concentrations (Ca2+ = 1.25 mM) were less marked than those of rabbit studied at physiological calcium (Ca2+ = 1.25 mM) but similar to those of rabbit studied at high calcium concentrations (Ca2+ = 15 mM). Removing the endocardial endothelial layer of rabbit papillary muscles did not alter the absolute changes in contractility caused by endothelin but shifted the dose-response curve to the left and markedly altered the effects of endothelin on twitch configuration characteristics. Thus, it would appear that endothelin increases contractility and modifies twitch configuration. It does so more at lower rather than higher extracellular calcium concentrations and in a species, such as rabbit, that responds more to interventions that increase intracellular calcium.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1860177 TI - Frog cardiac calsequestrin. Identification, characterization, and subcellular distribution in two structurally distinct regions of peripheral sarcoplasmic reticulum in frog ventricular myocardium. AB - Calsequestrin is a calcium-binding protein known to sequester calcium accumulated in the sarcoplasmic reticulum (SR) of muscle cells during relaxation. In the present study, we used affinity-purified antibodies to chicken cardiac calsequestrin to identify a 60,000-Da calsequestrin in frog myocardium. Like previously identified cardiac calsequestrins, it is enriched in cardiac microsomes, it is enriched by biochemical procedures previously used to purify cardiac and skeletal calsequestrins, and it exhibits a pH-dependent shift in its apparent Mr on a two-dimensional gel system. Finally, the NH2-terminal amino acid sequence of this 60,000-Da immunoreactive protein purified by fast protein liquid chromatography was identical to that of rabbit skeletal and canine cardiac calsequestrin. Thus, we conclude that this protein corresponds to the calsequestrin isoform in frog ventricular muscle. Frog calsequestrin was localized in discrete foci present at the periphery but absent from the central regions of frog ventricular myocytes as determined by immunofluorescence labeling. Immunoelectron microscopic labeling demonstrated that calsequestrin was confined to the lumen of two structurally distinct regions of the SR, where it was localized in the subsarcolemmal region of the myofibers. One of these appeared to correspond to the terminal SR previously reported to be closely apposed to the sarcolemma of frog myofibers. The other region, although close to the sarcolemma, was not physically joined to it and appeared to correspond to corbular SR. It generally is believed that frog cardiac SR does not provide activator Ca2+ required for excitation-contraction coupling. However, the identification of a calsequestrin isoform very similar to mammalian cardiac calsequestrin that is confined to specialized regions of frog cardiac SR lends support to the idea that frog cardiac SR has the ability to store Ca2+ and thus function in some capacity in frog cardiac muscle contraction. PMID- 1860178 TI - Contribution of endogenous endothelin to the extension of myocardial infarct size in rats. AB - Pathophysiological roles of endogenous endothelin have been studied from the viewpoint of its contribution to the extension of myocardial infarct size. A monoclonal antibody against endothelin 1 (AwETN40) suppressed changes induced by endothelin 1 and endothelin 2 but did not modify those by endothelin 3 in vivo or in vitro. Effects of AwETN40 on myocardial infarct size were investigated. Coronary ligation (1 hour) and reperfusion (24 hours) in rats caused infarction in 35% of the left ventricle. Repetitive or single administration of AwETN40 reduced the infarct size; an intravenous injection of 22.5 mg/kg of the antibody 5 minutes after coronary occlusion or 5 minutes before reperfusion reduced the size by 38% or 31% of the control, respectively. Plasma and tissue endothelin 1 and plasma big endothelin 1 in rats were measured at various stages after occlusion. Plasma endothelin 1 showed a fourfold increase 10 minutes after reperfusion (from 1.02 to 3.96 pg/ml) and had returned to the control value after 8 hours. Plasma big endothelin 1 showed changes similar to those of plasma endothelin 1. No significant changes in plasma endothelin 2 and endothelin 3 were observed. Cardiac tissue contained seven times as much endothelin 1 as the control value 1 hour after reperfusion (4.59 versus 33.1 pg/g tissue), and a high concentration (13.2 pg/g tissue) was maintained even after 48 hours. We concluded that an increase in endogenous endothelin 1 plays an important role in the extension of myocardial infarct size. PMID- 1860179 TI - Directional characteristics of action potential propagation in cardiac muscle. A model study. AB - Propagation of an elliptic excitation wave front was studied in a two-dimensional model of a thin sheet of cardiac muscle. The sheet model of 2.5 x 10 mm consisted of a set of 100 parallel cables coupled through a regular array of identical transverse resistors. The membrane dynamics was represented by a modified Beeler Reuter model. We defined the charging factor (CF) to represent by a single number the proportion of input current used to charge the membrane locally below threshold and showed that CF is inversely correlated with the time constant of the foot of the action potential (tau foot) during propagation on a cable. A safety factor of propagation (SF) was also defined for the upstroke of the action potential, with SF directly correlated with the maximum rate of depolarization (Vmax) and, for cablelike propagation, with propagation velocity. Propagation along the principal longitudinal axis of the elliptic wave front is cablelike but, in comparison with a flat wave front, transverse current flow provides a drag effect that somewhat reduces the propagation velocity, Vmax, SF, and CF. With a longitudinal-to-transverse velocity ratio of 3:1 or more, the wave front propagating along the principal transverse axis is essentially flat and is characterized by multiple collisions between successive pairs of input junctions on a given cable; Vmax, SF, and CF are larger than for longitudinal propagation, but CF is no longer correlated with tau foot. There are transient increases in propagation velocity and Vmax with distance from the stimulation site along both principal axes until stablized values are achieved, and a similar transient decrease in tau foot. Away from the principal axes, the action potential characteristics change progressively along the elliptic wave front.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860180 TI - Rapid attenuation ("fade") of the chronotropic response during vagal stimulation in the canine newborn. Evidence for a prominent neuropeptide Y effect. AB - We studied the time-dependent changes in the response of heart rate (sinus cycle length) to 30-second trains of vagal stimulation (8 Hz), repeated every 2 minutes, in canine neonates aged 7.1 +/- 2.5 (mean +/- SD) days. The first vagal train prolonged the sinus cycle length by 58 +/- 35%, but the response was attenuated during subsequent trains (98 +/- 5% inhibition of the vagal response after only 6.4 +/- 1.7 trains). After 40 minutes, complete restoration of the chronotropic response could be demonstrated. Receptor desensitization could be excluded as the reason for the attenuation by demonstrating preserved responses to exogenous acetylcholine. Neuropeptide Y, a sympathetic cotransmitter that has been shown to attenuate parasympathetic responses (thought to be the result of inhibition of the release of acetylcholine from parasympathetic nerve terminals), was administered (50 micrograms/kg) to eight newborns. Exogenous neuropeptide Y resulted in a complete inhibition of the chronotropic response to vagal stimulation, with restoration of the chronotropic response occurring after 60 minutes. Thus, exogenous neuropeptide Y mimicked the effect of repetitive vagosympathetic trunk stimulation; this finding suggested that neuropeptide Y release from sympathetic nerves during repetitive vagosympathetic trunk stimulation may have resulted in the observed attenuation of the vagal chronotropic response. To test this hypothesis, seven other newborns underwent chemical sympathectomy (50 mg/kg i.p. 6-hydroxydopamine for 3 days, tyramine verified), and in these newborns, stable chronotropic responses to repetitive vagosympathetic trunk stimulation were observed (inhibition of vagal response was 0 +/- 18% after 10 stimulus trains).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860181 TI - Effects of MK-801 on cerebral regional oxygen consumption in focal cerebral ischemia in rats. AB - This investigation tested in rats whether MK-801, an N-methyl-D-aspartate receptor antagonist, would improve the balance of oxygen supply and consumption in the focal ischemic area of the brain induced by occlusion of the middle cerebral artery. Fifteen minutes after middle cerebral artery occlusion, 5 mg/kg MK-801 was administered intravenously to the MK-801 group (n = 12), and normal saline was given to the control group (n = 12). One hour after the occlusion in each group, regional cerebral blood flow was determined in six rats using [14C]iodoantipyrine, and regional arterial and venous oxygen saturations were determined using a microspectrophotometric technique in the other six rats. In both groups of animals, the cerebral blood flow of the ischemic cortex was significantly lower than that of the contralateral cortex (36 +/- 16 [SD] and 67 +/- 14 ml/min/100 g for the control group; 33 +/- 10 and 58 +/- 11 ml/min/100 g for the MK-801 group, respectively). Oxygen extraction was significantly higher in the ischemic cortex (8.8 +/- 2.1 ml O2/100 ml blood) than in the contralateral cortex (5.6 +/- 0.3) for the control group. However, for the MK-801 group, there was no significant difference between the ischemic cortex (6.1 +/- 1.0) and the contralateral cortex (5.7 +/- 1.1). Oxygen extraction in the ischemic cortex of the MK-801 group was significantly lower than that of the control group. Calculated ischemic regional oxygen consumption was similar to the nonischemic values in the control group, whereas the ischemic value was reduced to 61% of the value of the contralateral cortex in the MK-801 group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860182 TI - Intrarenal hemodynamics in patients with essential hypertension. AB - Intrarenal hemodynamics were estimated clinically in essential hypertension. Two week studies were performed in 30 patients with essential hypertension who were given a regular sodium diet in the first week and a sodium-restricted diet in the second week. Intrarenal hemodynamic parameters such as afferent arteriolar (preglomerular) resistance, efferent arteriolar resistance, and glomerular hydrostatic pressure were calculated from renal clearances and plasma total protein concentration measured on the last day of the regular sodium diet. Calculations were based on Gomez's equations with the assumption that the gross filtration coefficient of glomerular capillaries was normal. The increase in afferent arteriolar resistance (8,100 +/- 500 dyne.sec.cm-5) was significantly correlated with an elevation in mean arterial pressure (120 +/- 2 mm Hg), whereas glomerular pressure (56 +/- 1 mm Hg) and efferent arteriolar resistance (2,500 +/ 100 dyne.sec.cm-5) remained normal. The renal function curve (pressure natriuresis relation) was drawn by plotting urinary sodium excretion on the y axis as a function of mean arterial pressure on the x axis, both of which were measured on the last 3 days of each week. The extrapolated x intercept (107 +/- 2 mm Hg) of the renal function curve was strongly correlated in a 1:1 fashion with the sum of the arterial pressure drop from the aorta to the renal glomeruli plus the opposing pressures against glomerular filtration at glomeruli (r = 0.7, p less than 0.001) on the regular sodium diet, suggesting that the difference between mean arterial pressure on the regular sodium diet and the extrapolated x intercept represented the effective filtration pressure across the glomerular capillaries on the regular sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860184 TI - Arterial wall and smooth muscle cell development in young Wistar rats and the effects of surgical denervation. AB - Development of the muscular saphenous artery and the effect of surgical denervation on normal development was investigated in young rats at 3 and 6 weeks of age. During this interval, the weight and blood pressures (systolic, diastolic, and mean) of the animals increased significantly. The tunica media of the artery and the lumen increased significantly with age, but the proportion of smooth muscle cell to paracellular matrix did not alter. Computer-assisted three dimensional reconstructions were used to investigate the smooth muscle cells. They increased significantly in length, volume, and angle of orientation within the vessel wall with age but maintained an approximate surface area-to-volume ratio. The cells in any one vessel tended to be oriented in either a clockwise or counterclockwise direction. The size of the nucleus also increased significantly in length and volume with age, but an approximate surface area-to-volume ratio and a constant nucleocytoplasmic ratio were maintained. The nuclei tended to be eccentrically located, with less than half of all nuclei wholly within the middle third of the cell. Surgical denervation at 10 days of age resulted in abnormalities of growth in vessel dimensions, thinner tunica media at 3 weeks (denervated 11 days previously), and smaller lumen at 6 weeks (denervated 32 days previously). Elevated amounts of paracellular matrix occurred in both age groups, but denervation did not alter smooth muscle cell size. In the 3-week-old animals, denervation resulted in smooth muscle cells with hypertrophied nuclei. This may account for the increase in growth of the tunica media between 3 and 6 weeks of age in the denervated artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860183 TI - Morphology of electrophysiologically identified junctions between Purkinje fibers and ventricular muscle in rabbit and pig hearts. AB - Purkinje fiber-ventricular muscle (PV) junctions were identified by extracellular recording in isolated, superfused preparations from rabbit and pig hearts. Microelectrode recordings from different cell types at the PV junctions were obtained, and the cells recorded from were retrieved microscopically. To this end 26 tissue blocks were serially sectioned at 4 microns. Microscopic identification of the very cell recorded from was obtained in five of seven Purkinje, five of 16 transitional, and two of two ventricular muscle cell recordings. In addition, some tissue blocks from both junctional and nonjunctional sites identified only by extracellular recording were examined in serial sections. Transitional cells in the rabbit heart are thin, broad bandlike cells (30-35 by 3-5 microns) arranged in one or two sheets in the subendocardium between the Purkinje layer and ventricular mass. Transitional cells are coupled via short, thin strands to both Purkinje and ventricular muscle cells. A second type of PV coupling was observed frequently in the pig, but in only one of 21 cases in the rabbit. Here, a short, linear segment of small transitional cells connected large-diameter Purkinje cells to ventricular muscle cells. Distances found between Purkinje transitional cell coupling sites and transitional cell-ventricular muscle coupling sites varied from 100 to 1,000 microns in the rabbit heart and from 50 to several hundred micrometers in the pig heart. Action potentials from transitional cells typically showed multiple components in their upstroke. Both our morphological and electrophysiological findings are compatible with the existence of a relatively high-resistance barrier between Purkinje and transitional cells and between transitional and ventricular muscle cells. PMID- 1860185 TI - Catecholamine release from bovine adrenal chromaffin cells during anoxia or metabolic inhibition. AB - A significant release of catecholamines within the heart has been observed during myocardial ischemia. Because this can be markedly inhibited by amine-uptake blocking agents, it has been suggested that its mechanism is a carrier-mediated efflux from neurons, which is not operative under normal conditions. The present work examined this release process in chromaffin cells isolated from the bovine adrenal medulla, a model system for studying the sympathetic nervous system. Chromaffin cells in primary culture retained normal secretory responses for up to 7 days. Conditions designed to mimic ischemia, that is, anoxia or metabolic inhibition, resulted in a significant release of catecholamines. This release was shown to be independent of extracellular calcium but, in contrast to the release observed in ischemic hearts, was not inhibited by amine-uptake blockers. Electrophoresis with immunoblotting demonstrated that significant levels of the chromaffin granule protein, chromogranin A, were released during metabolic inhibition, indicative of an exocytotic mechanism. However, there was no release of the cytosolic protein, lactate dehydrogenase, indicating that there was no concomitant breakdown of the cell membrane. These results provide evidence for an exocytotic release of catecholamines mediated by the direct action of conditions of metabolic inhibition. PMID- 1860186 TI - Differential effects of transforming growth factor-beta 1 and phorbol myristate acetate on cardiac fibroblasts. Regulation of fibrillar collagen mRNAs and expression of early transcription factors. AB - Cardiac fibroblasts are responsible for synthesis and deposition of fibrillar collagen types I and III. Transforming growth factor-beta 1 (TGF-beta 1) has been proved to increase collagen biosynthesis in various systems, both in vivo and in vitro. We have investigated the effect of TGF-beta 1 on collagen gene expression in cultured cardiac fibroblasts and have compared this effect with that of a mitogenic agent, phorbol myristate acetate (PMA). The regulation of collagen types I and III gene expression was examined by using cDNA probes to rat alpha 2 (I) and mouse alpha 1 (III) procollagens. Quiescent cultured cardiac fibroblasts from rabbit heart were treated with TGF-beta 1 (10-15 ng/ml) and PMA (200 ng/ml). After 24 hours of treatment with TGF-beta 1, the abundance of mRNA for pro-alpha 2 (I) and pro-alpha 1 (III) collagens was increased by 112% (p less than 0.001) and 97% (p = 0.05), respectively, in treated fibroblasts compared with untreated cells. However, PMA-treated cells showed an opposite response: a 42% (p = 0.01) decrease in mRNA levels for pro-alpha 2 (I) collagen was observed. Immunofluorescent staining of cardiac fibroblasts in culture with anti-type I collagen antibody showed that alterations in mRNA levels led to altered collagen synthesis: cellular collagen was relatively increased in TGF-beta 1-treated cells and significantly diminished in PMA-treated cells. The abundance of mRNA for pro alpha 1 (III) collagen was not affected by PMA treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860187 TI - Inhibitory effects of procainamide on sympathetic nerve activity in humans. AB - In experimental animals, procainamide causes hypotension and reductions in efferent vasoconstrictor sympathetic outflow that may result from ganglionic blockade or central nervous system sympathetic inhibition. To test the hypothesis that procainamide decreases sympathetic nerve activity (SNA) in humans, we recorded postganglionic SNA in seven normal subjects in the baseline state and during infusions of procainamide HCl at 50 mg/min (loading) and 8 mg/min (maintenance). At the end of the loading infusion, mean arterial pressure (MAP) had decreased from 88.5 +/- 2.4 (mean +/- SEM) to 81.5 +/- 3.2 mm Hg (p less than 0.05), central venous pressure from 6.7 +/- 0.7 to 5.4 +/- 0.9 mm Hg (p less than 0.05), forearm vascular resistance (FVR) from 28 +/- 4.8 to 22.3 +/- 5.1 resistance units (p less than 0.05), and SNA from 259 +/- 47 to 94 +/- 26 units/min (p less than 0.05). These changes persisted during the maintenance infusion. Increased levels of SNA, FVR, and MAP provoked by the cold pressor test were reduced significantly by intravenous procainamide. In eight other subjects, intravenous procainamide HCl (15 mg/kg at 50 mg/min) caused dose-dependent inhibition of SNA that reversed as blood concentrations fell during drug washout. To determine if procainamide causes direct vasodilation, in nine subjects, graded infusions were delivered into the brachial artery at doses that produced no systemic effect. Ipsilateral FVR tended to increase during local intra-arterial infusion of procainamide. These data show that intravenous procainamide causes hypotension, vasodilation, and sympathetic withdrawal. Vasodilation does not result from a direct vasorelaxant effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860188 TI - Influence of topically applied adrenergic agents on cochlear blood flow. AB - This study was designed to assess the role of adrenergic receptors in the control of cochlear blood flow. Laser Doppler flowmetry was used to determine the effects of adrenergic drugs topically applied to the round window membrane of the cochlea. The relative influence of the various receptor types (alpha 1, alpha 2, beta 1, and beta 2) was examined by a selection of agonists and antagonists. The agonists norepinephrine and epinephrine, which have mixed alpha- and beta receptor effects, and phenylephrine, a strong alpha 1-agonist, all induced a dose dependent reduction in cochlear blood flow. The agonists isoproterenol (beta active), salbutamol (alpha 2-active) had no effect on cochlear blood flow. Of the antagonists, when tested alone, only the selective alpha 1-antagonist prazosin had a direct effect on cochlear blood flow, demonstrating an increase in cochlear blood flow. The selective alpha 2-antagonist idazoxan, the beta-antagonist propranolol, and the unselective alpha-antagonist phentolamine had no effect on cochlear blood flow. Interaction studies of agonists and antagonists were performed to specifically define the receptor subclasses responsible for the cochlear blood flow increases with norepinephrine and epinephrine. The results are consistent with the presence of an alpha 1-adrenergic sympathetic control of cochlear blood flow. PMID- 1860189 TI - Suppression of time-dependent outward current in guinea pig ventricular myocytes. Actions of quinidine and amiodarone. AB - Prolongation of cardiac action potentials may mediate some of the arrhythmia suppressing and arrhythmia-aggravating actions of antiarrhythmic agents. In this study, suppression of time-dependent outward current by quinidine and amiodarone was assessed in guinea pig ventricular myocytes. The net time-dependent outward current contained at least two components: a slowly activating, La(3+)-resistant delayed rectifier current (IK) and a rapidly activating, La(3+)-sensitive current. Quinidine block of total time-dependent outward current during clamp steps to positive potentials was relieved as a function of time, whereas that induced by amiodarone was enhanced. In contrast, at negative potentials, suppression of current, whereas amiodarone reduced IK but not the La(3+) sensitive current, suggesting that differential block of the two components of time-dependent current underlies the distinct effects of the two agents. In contrast to these disparate effects on total time-dependent outward current, steady-state reduction of IK by both drugs increased at positive voltages and saturated at approximately +40 mV; the voltage dependence of block by quinidine (17% per decade, +10 to +30 mV) was steeper than that by amiodarone (5% per decade, +10 to +20 mV). Block by quinidine was time dependent at negative potentials: on stepping from +50 to -30 mV, block initially increased very rapidly, and subsequent deactivation of IK was slowed. This effect was not seen with amiodarone. At -80 mV, quinidine block was relieved with a time constant of 40 +/- 15 msec (n = 4, twin-pulse protocol). The effects of quinidine on IK were compatible with neither a purely voltage-dependent model of quinidine binding nor a model incorporating both voltage- and state-dependent binding of quinidine to delayed rectifier channels having only one open state. The voltage- and time dependent features of quinidine block were well described by a model in which quinidine has greater affinity for one of two open states of the channel. We conclude that the effects of quinidine and amiodarone on time-dependent outward current reflects block of multiple channels. Quinidine block of IK was far more voltage dependent than that produced by amiodarone, suggesting the drugs act by different mechanisms. PMID- 1860191 TI - Comments on "Importance of the great vessels in the genesis of the electrocardiogram" (Circ Res 1990;66:1081-1087) PMID- 1860190 TI - Human nonmuscle myosin heavy chains are encoded by two genes located on different chromosomes. AB - We report the cloning of cDNAs encoding two different human nonmuscle myosin heavy chains designated NMMHC-A and NMMHC-B. The mRNAs encoding NMMHC-A and NMMHC B are both 7.5 kb in size but are shown to be the products of different genes, which are localized to chromosome 22q11.2 and chromosome 17q13, respectively. In aggreement with previously reported results using avian tissues, we show that the mRNAs encoding the two myosin heavy chain isoforms are differentially expressed in rat nonmuscle and muscle tissues as well as in a number of human cell lines. The cDNA sequence encoding the 5' portion of the NMMHC-A isoform completes the previously published 3' cDNA sequence encoding a human myosin heavy chain, thus providing the cDNA sequence encoding the entire NMMHC-A amino acid sequence. Comparison of this sequence to cDNA clones encoding the amino-terminal one third of the NMMHC-B sequence (amino acids 58-718) shows them to be 89% identical at the amino acid level and 74% identical at the nucleotide level. PMID- 1860192 TI - Nonrheumatic atrial fibrillation. Risk of stroke and role of antithrombotic therapy. PMID- 1860193 TI - Cardiovascular neural regulation explored in the frequency domain. AB - A consistent link appears to exist between predominance of vagal or sympathetic activity and predominance of HF or LF oscillations, respectively: RR variability contains both of these rhythms, and their relative powers appear to subserve a reciprocal relation like that commonly found in sympathovagal balance. In this respect, it is our opinion that rhythms and neural components always interact, just like flexor and extensor tones or excitatory and inhibitory cardiovascular reflexes, and that it is misleading to separately consider vagal and sympathetic modulations of heart rate. In humans and experimental animals, functional states likely to be accompanied by an increased sympathetic activity are characterized by a shift of the LF-HF balance in favor of the LF component; the opposite occurs during presumed increases in vagal activity. In addition, LF oscillation evaluated from SAP variability appears to be a convenient marker of the sympathetic modulation of vasomotor activity. Although based on indirect markers, the exploration in the frequency domain of cardiovascular neural regulation might disclose a unitary vision hard to reach through the assemblage of more specific but fragmented pieces of information. PMID- 1860195 TI - Left cardiac sympathetic denervation in the therapy of congenital long QT syndrome. A worldwide report. AB - BACKGROUND: Long QT syndrome (LQTS) is a congenital disorder accompanied by a high incidence of sudden cardiac death. beta-Adrenergic blockade is the therapy of choice, and it is successful in 75-80% of patients. For those in whom cardiac events (syncope or cardiac arrest) are not prevented by beta-blockade, experimental studies suggest that left cardiac sympathetic denervation (LCSD) may be useful. METHODS AND RESULTS: We identified 85 LQTS patients worldwide who underwent LCSD, and we provide here the first large-scale evaluation of its efficacy. The time interval between the first cardiac event and LCSD and the follow-up period after LCSD were similar (5.6 +/- 6.1 versus 5.9 +/- 5.7 years). The mean age of the patients at surgery was 20 +/- 13 years. LCSD was followed by highly significant (p less than 0.0001) decreases in the number of patients with cardiac events (from 99% to 45%), in the number of cardiac events per patient (from 22 +/- 32 to 1 +/- 3), and in the number of patients with five or more cardiac events (from 71% to 10%). There were seven sudden deaths (8%), and the 5 year survival rate was 94%. The marked reduction in the incidence of tachyarrhythmic syncope suggests that LCSD has also reduced the risk for sudden death in this high-risk population. CONCLUSIONS: The present findings demonstrate that for LQTS patients who continue with syncope or cardiac arrest despite the use of beta-blockers, LCSD is a very effective therapy. PMID- 1860194 TI - Dipyridamole thallium-201 scintigraphy as a preoperative screening test. A reexamination of its predictive potential. Study of Perioperative Ischemia Research Group. AB - BACKGROUND: We examined the value of dipyridamole thallium-201 (201Tl) scintigraphy as a preoperative screening test for perioperative myocardial ischemia and infarction. METHODS AND RESULTS: We prospectively studied 60 patients undergoing elective vascular surgery. We performed 201Tl scintigraphy preoperatively and blinded all treating physicians to the results. Historical, clinical, laboratory, and physiological data were gathered throughout hospitalization. Myocardial ischemia was assessed during the intraoperative period using continuous 12-lead electrocardiography (ECG) and transesophageal echocardiography (TEE) and during the postoperative period using continuous two lead ambulatory ECG. Adverse cardiac outcomes (cardiac death, myocardial infarction, unstable angina, severe ischemia, or congestive heart failure) were assessed daily throughout hospitalization. Twenty-two patients (37%) had defects that improved or reversed on delayed scintigrams (redistribution defects), 18 (30%) had persistent defects, and 20 (33%) had no defects on 201Tl scintigraphy. There was no association between redistribution defects and adverse cardiac outcomes: 54% (seven of 13) of adverse outcomes occurred in patients without redistribution defects, and the risk of an adverse outcome was not significantly increased in patients with redistribution defects (relative risk 1.5, 95% confidence interval 0.6-3.9, p = 0.43). Consistent with these findings, there was also no association between redistribution defects and perioperative ischemia: 54% (19 of all 35) of perioperative ECG and TEE ischemic episodes and 58% (14 of 24) of severe ischemic episodes occurred in patients without redistribution defects. The sensitivity of 201Tl scintigraphy for perioperative ischemia and adverse outcomes ranged from 40% to 54%, specificity from 65% to 71%, positive predictive value from 27% to 47% and negative predictive value from 61% to 82%. CONCLUSIONS: These results differ from those of previous studies and suggest that the routine use of 201Tl scintigraphy for preoperative screening of patients undergoing vascular surgery may not be warranted. PMID- 1860196 TI - Left ventricular thrombus in anterior acute myocardial infarction after thrombolysis. A GISSI-2 connected study. AB - BACKGROUND: Streptokinase reduces the incidence of left ventricular thrombosis after acute myocardial infarction. However, it is unknown whether a similar effect can be obtained with different thrombolytic agents and whether subcutaneous calcium heparin can have an additional efficacy. METHODS AND RESULTS: To compare the effects of two different thrombolytic agents combined or not with heparin on the incidence and features of left ventricular thrombi and their related embolic events, we performed a GISSI-2 ancillary echocardiographic study (the first echocardiogram obtained within 48 hours of symptoms onset and the second before hospital discharge) that enrolled 180 consecutive patients (mean age, 63 +/- 11 years, 142 men) with a first anterior acute myocardial infarction. Patients were randomized into four groups of treatment: recombinant tissue-type plasminogen activator (rt-PA) (n = 47), rt-PA plus heparin (n = 45), streptokinase (n = 39), and streptokinase plus heparin (n = 49). Left ventricular thrombosis was observed in 51 of 180 patients (28%). No significant differences were found concerning the incidence of thrombi in the four treatment groups. Mural shape of left ventricular thrombi was found more frequently than the protruding shape (71% versus 29% at the first examination, 64% versus 36% at the second), particularly in heparin-treated patients (93% versus 7% at first examination, 70% versus 30% at the second). Only one embolic event (0.5%) occurred during the hospitalization. CONCLUSIONS: We conclude that 1) the rate of left ventricular thrombi does not differ in patients with acute myocardial infarction treated either with streptokinase or rt-PA, 2) subcutaneous heparin, when begun 12 hours after intravenous thrombolysis, does not appear to further reduce the occurrence of thrombi but seems to influence the shape of left ventricular thrombi, and 3) during the predischarge period, embolic events are rare in patients treated by thrombolysis. PMID- 1860197 TI - Starting aspirin therapy after operation. Effects on early graft patency. Department of Veterans Affairs Cooperative Study Group. AB - BACKGROUND: Although aspirin therapy started before operation improves vein graft patency after coronary artery bypass grafting, it also causes bleeding. The objective of this prospective, centrally directed, randomized, double-blind, placebo-controlled trial was to compare the effects of aspirin therapy started before operation with aspirin started 6 hours after operation on early (7-10-day) graft patency. METHODS AND RESULTS: Patients were randomized to receive either aspirin 325 mg or placebo the night before surgery; after operation, all patients received aspirin 325 mg daily, with the first dose administered through the nasogastric tube 6 hours after operation. Angiography was performed in 72% of the analyzed patients an average of 8 days after operation, and the primary end point was saphenous vein graft patency in 351 patients. Internal mammary artery graft patency was also assessed in 246 patients because many individuals received both internal mammary artery and vein grafts. In the patients given preoperative aspirin, the vein graft occlusion rate was 7.4 +/- 1.3% compared with 7.8 +/- 1.5% in those who received preoperative placebo (p = 0.871). In the subgroup of patients receiving Y grafts, 0.0% of the grafts were occluded in the preoperative aspirin group compared with 7.0 +/- 3.6% in the preoperative placebo group (p = 0.066). The internal mammary artery occlusion rate was 0.0% (0 of 131) in the aspirin group compared with 2.4 +/- 1.4% (three of 125) in the placebo group (p = 0.081). Patients in the aspirin group received more transfusions than those in the placebo group (median, 900 versus 725 ml, p = 0.006). The reoperation rate for bleeding in the aspirin group was 6.3% compared with 2.4% in the placebo group (p = 0.036). Median chest tube drainage within the first 6 hours after operation was 500 ml in the aspirin group compared with 448 ml in the placebo group (p = 0.011). CONCLUSIONS: Thus, preoperative aspirin is associated with increased bleeding complications and offers no additional benefit in early vein graft patency compared with starting aspirin therapy 6 hours after operation. There was a trend, although not significant, toward improved early patency for Y grafts and internal mammary artery grafts with preoperative aspirin. PMID- 1860198 TI - Stroke Prevention in Atrial Fibrillation Study. Final results. AB - BACKGROUND: Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke. METHODS AND MAIN RESULTS: The Stroke Prevention in Atrial Fibrillation Study, a multicenter, randomized trial, compared 325 mg/day aspirin (double-blind) or warfarin with placebo for prevention of ischemic stroke and systemic embolism (primary events), and included 1,330 inpatients and outpatients with constant or intermittent atrial fibrillation. During a mean follow-up of 1.3 years, the rate of primary events in patients assigned to placebo was 6.3% per year and was reduced by 42% in those assigned to aspirin (3.6% per year; p = 0.02; 95% confidence interval, 9-63%). In the subgroup of warfarin-eligible patients (most less than 76 years old), warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67% (warfarin versus placebo, 2.3% versus 7.4% per year; p = 0.01; 95% confidence interval, 27-85%). Primary events or death were reduced 58% (p = 0.01) by warfarin and 32% (p = 0.02) by aspirin. The risk of significant bleeding was 1.5%, 1.4%, and 1.6% per year in patients assigned to warfarin, aspirin, and placebo, respectively. CONCLUSIONS: Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation. Because warfarin-eligible patients composed a subset of all aspirin eligible patients, the magnitude of reduction in events by warfarin versus aspirin cannot be compared. Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin, and the trial is continuing to address this issue. Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke. PMID- 1860199 TI - Post-myocardial infarction mortality in patients with ventricular premature depolarizations. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Pilot Study. AB - BACKGROUND: Among survivors of acute myocardial infarction, frequent and repetitive ventricular premature depolarizations (VPDs) detected on ambulatory monitoring contribute independently to the risk of all-cause mortality and sudden death. Apart from the beta-blockers, no antiarrhythmic drug has been reliably demonstrated to reduce mortality among patients with VPDs. A pilot study was undertaken to gather data to aid in the design of a multicenter trial of amiodarone for the reduction of mortality from cardiac arrhythmias in such patients. METHODS AND RESULTS: Seventy-seven patients with acute myocardial infarction within the previous 6-30 days and 10 or more VPDs/hr or one or more runs of ventricular tachycardia on 24-hour electrocardiographic recording were randomized in a double-blind fashion in a 2:1 amiodarone-to-placebo ratio. The loading dose was 10 mg/kg/day for 3 weeks. The maintenance dose was 300-400 mg/day with reductions at 4-month intervals in response to VPD suppression, excessive plasma levels, or toxicity. VPD suppression at 1 week and 2 weeks was 63% and 85%, respectively, on amiodarone and 17% and 27%, respectively, on placebo. Apart from thyroid-stimulating hormone elevation and skin reactions, no side effects occurred more frequently with amiodarone. The study drug was stopped for side effects or noncompliance in 35% of amiodarone patients and 34% of placebo patients. Patients were followed for a maximum of 2 years (mean, 20 months). Arrhythmic death or resuscitated ventricular fibrillation occurred in two of 48 amiodarone patients (6%) and four of 29 placebo patients (14%), whereas the rates of all-cause mortality were five of 48 (10%) and six of 29 (21%), respectively. CONCLUSIONS: Amiodarone, in moderate loading and maintenance dosages with adjustments in response to plasma levels, VPD suppression, and side effects, results in effective VPD suppression and acceptable levels of toxicity. PMID- 1860200 TI - Predictors of first discharge and subsequent survival in patients with automatic implantable cardioverter-defibrillators. AB - BACKGROUND: Two hundred eighteen patients were evaluated in a two-phase approach (time to first appropriate discharge, survival after discharge) to identify factors that may be related to maximal benefit derived from use of an automatic implantable cardioverter-defibrillator (AICD). METHODS AND RESULTS: One hundred ninety-seven patients survived implantation of AICD, with or without concomitant cardiac surgery. One hundred five patients had an AICD discharge associated with syncope, presyncope, documented sustained ventricular tachycardia or fibrillation, or sleep at 9.1 +/- 11.1 months after implantation. Patients survived 23.8 +/- 18.0 months after AICD discharge. Left ventricular dysfunction (p = 0.008 for ejection fraction less than 25%) was associated with earlier AICD discharge and shortened survival after AICD discharge (p = 0.008 for ejection fraction less than 25%; p = 0.01 for New York Heart Association functional class III and IV). beta-Blocker administration (p = 0.006) and coronary bypass surgery (p = 0.06) were associated with later AICD discharge. Coronary bypass surgery (p = 0.035) but not beta-blockers was associated with more prolonged survival after AICD discharge. CONCLUSIONS: These data suggest that a relatively easy algorithm can be applied to predict which patient will benefit most from AICD implantation. PMID- 1860201 TI - Radiofrequency catheter ablation of the atrioventricular junction from the left ventricle. AB - BACKGROUND: The purpose of this study was to describe a new technique for catheter ablation of the atrioventricular junction using radiofrequency energy delivered in the left ventricle. METHODS AND RESULTS: Catheter ablation of the atrioventricular (AV) junction using a catheter positioned across the tricuspid annulus was unsuccessful in eight patients with a mean +/- SD age of 51 +/- 19 years who had AV nodal reentry tachycardia (three patients), orthodromic tachycardia using a concealed midseptal accessory pathway, atrial tachycardia, atrial flutter (two patients), or atrial fibrillation. Before attempts at catheter ablation of the AV junction, each patient had been refractory to pharmacological therapy, and four had failed attempts at either catheter modification of the AV node using radiofrequency energy or surgical and catheter ablation of the accessory pathway. Conventional right-sided catheter ablation of the AV junction using radiofrequency energy in six patients and both radiofrequency energy and direct current shocks in two patients was ineffective. The mean amplitude of the His bundle potential recorded at the tricuspid annulus at the sites of unsuccessful AV junction ablation was 0.1 +/- 0.08 mV, with a maximum His amplitude of 0.03-0.28 mV. A 7F deflectable-tip quadripolar electrode catheter with a 4-mm distal electrode was positioned against the upper left ventricular septum using a retrograde aortic approach from the femoral artery. Third-degree AV block was induced in each of the eight patients with 20-36 W applied for 15-30 seconds. The His bundle potential at the sites of successful AV junction ablation ranged from 0.06 to 0.99 mV, with a mean of 0.27 +/- 0.32 mV. There was no rise in the creatine kinase-MB fraction and no complications occurred. An intrinsic escape rhythm of 30-60 beats/min was present in seven of the eight patients. Each patient received a permanent pacemaker and has been asymptomatic during 3-13 months of follow-up. CONCLUSIONS: Catheter ablation of the AV junction can be achieved effectively and safely using radiofrequency energy delivered in the left ventricle when the conventional right-sided approach is unsuccessful. PMID- 1860202 TI - Clinical implications of late proven patency after successful coronary angioplasty. AB - BACKGROUND: The introduction of percutaneous transluminal coronary angioplasty (PTCA) has changed the pattern of intervention in coronary artery disease. However, the long-term results in patients undergoing successful, elective, native-vessel PTCA are not yet fully characterized. Because the healing and subsequent proliferative response after angioplasty are time related, it was the purpose of the present study to determine the long-term outcome in patients whose dilated arteries have been demonstrated to be patent 4-12 months after successful, uncomplicated PTCA. METHODS AND RESULTS: The patients were grouped on the basis of the 4-12 month catheterization into those whose vessels were angiographically "normal" or had luminal irregularities only at the PTCA sites (396 patients), those whose vessels also had luminal irregularities elsewhere with or without PTCA site luminal irregularities (680 patients), and those with significant obstructive disease (more than 50% diameter narrowing) at sites other than the PTCA sites (426 patients). Of 1,502 such patients, long-term follow-up was available in 1,491. At the time of the original angioplasty, the normal patients had a 1.8% incidence of multivessel disease; luminal irregularity patients, 9.4%; and obstructive disease patients, 58.7%. At angiographic restudy, 16.4% of the obstructive disease patients continued to have multivessel disease. The patients were followed for the events of death, myocardial infarction, coronary surgery, and repeat PTCA. The 6-year survival rate was 95%; cardiac survival, 96%; and freedom from all events, 65%. The strongest correlate of events during follow-up was the angiographic status of the undilated segments. At 6 years, freedom from cardiac events was noted in 77% of the normal group, 61% of the luminal irregularity group, and 55% of the obstructive disease group. Diabetes and hypertension were also independent correlates of events. CONCLUSIONS: Results from the present study show that associated disease in undilated segments is a strong predictor of late events in patients after successful, uncomplicated, reatenosis-free PTCA. However, the need for further revascularization was frequent even in patients without obstructive disease. Completeness of revascularization is appropriate when possible, and limiting progression of coronary disease at sites remote from those dilated should improve on these late results. PMID- 1860203 TI - Intraoperative transesophageal Doppler color flow imaging used to guide patient selection and operative treatment of ischemic mitral regurgitation. AB - BACKGROUND: Intraoperative transesophageal Doppler color flow imaging (TDCF) affords the opportunity to assess mitral valve competency immediately before and after cardiopulmonary bypass (CPB). The purpose of this study was to assess the utility of TDCF to assist in the selection and operative treatment of ischemic mitral regurgitation (MR). METHODS AND RESULTS: Two hundred forty-six patients undergoing surgery for ischemic heart disease were prospectively studied. All had preoperative cardiac catheterization. Catheterization and pre-CPB TDCF were discordant in their estimation of MR in 112 patients (46%). Compared with patients in whom both techniques agreed in estimation of MR, patients with discordance in MR were more likely to have had unstable clinical syndromes at the time of catheterization (79% versus 40%, p less than 0.05) or to have received thrombolytics (16% versus 8%, p less than 0.05). Pre-CPB TDCF resulted in a change in the operative plan with respect to the mitral valve in 27 patients (11%). Because less MR was found by TDCF than catheterization, 22 patients had only coronary bypass grafting when combined coronary bypass and mitral valve surgery had been planned. Because more MR was found by TDCF than catheterization, five patients had combined coronary bypass and mitral valve surgery when coronary bypass alone had been planned. Unsatisfactory results noted by TDCF following mitral valve surgery in five patients resulted in immediate corrective surgery. Cox regression analysis identified residual MR at the completion of surgery to be an important predictor of survival (chi 2 = 21.4) after surgery--more important than patient age (chi 2 = 8.3) or left ventricular ejection fraction (chi 2 = 5.3). CONCLUSIONS: These results indicate that TDCF is useful in guiding patient selection and operative treatment of ischemic MR and that in such patients, intraoperative TDCF should be performed routinely. PMID- 1860204 TI - Blood platelet count and function are related to total and cardiovascular death in apparently healthy men. AB - BACKGROUND: Experimental animal and clinical studies indicate that blood platelets have an important role in atherosclerosis and formation of thrombi. Prospective studies presenting evidence of an association between blood platelet count and cardiovascular mortality have not been performed. METHODS AND RESULTS: From 1973 to 1975, blood platelets were counted, and their responsiveness to aggregating agents was studied in healthy middle-aged men. The aim was to assess the possible association between these variables and coronary heart disease. At 13.5 years of follow up, a significantly higher coronary heart disease mortality was observed among the 25% of subjects with the highest platelet counts. Platelet aggregation performed in a random subsample (150 of the 487 men), moreover, revealed that the 50% with the most rapid aggregation response after ADP stimulation had significantly increased coronary heart disease mortality compared with the others. These associations could not be explained by differences in age, lipids, blood pressure, or smoking habits. CONCLUSIONS: The present study is the first to present conclusive, prospective evidence of an association between platelet concentration and aggregability and long-term incidence of fatal coronary heart disease in a population of apparently healthy middle-aged men. PMID- 1860205 TI - Hemodynamics and coronary blood flow during exercise after coronary artery bypass grafting with internal mammary arteries in children with Kawasaki disease. AB - BACKGROUND: Saphenous vein grafts (SVG) and internal mammary artery (IMA) grafts have been used for coronary artery bypass grafting. In adult patients with bypass grafting for atherosclerotic coronary artery disease, IMA grafts have been reported to have long-term patency; however, results are conflicting on whether the graft is sufficient to meet increased myocardial oxygen demand during exercise. There have been no studies on hemodynamics and blood flow during exercise after bypass grafting with IMA in pediatric patients with Kawasaki disease. METHODS AND RESULTS: We studied 17 pediatric patients with Kawasaki disease (average age, 7.5 +/- 3.1 years), who underwent coronary artery bypass grafting with the IMA. The average number of coronary artery bypass grafts was 2.1 +/- 0.7/patient. For all patients, the left IMA was anastomosed to the left anterior descending coronary artery; for eight patients, the right IMA was also anastomosed to the right coronary artery. In addition, 11 SVGs were used. The postoperative patency rates after 1 month were 100% with the IMA graft and 91% with SVG. One year after the operation, the patency rates were 100% with IMA and 50% with SVG. Hemodynamics during exercise were measured with a bicycle ergometer, and coronary sinus blood flow was measured by the continuous thermodilution method in six patients. The relation between delta LVEDP (the difference between left ventricular end-diastolic pressure at rest and during exercise) and delta SVI (the difference between the stroke volume index at rest and during exercise) was analyzed. Four of six patients had reduced cardiac function before operation (delta LVEDP, positive; delta SVI, negative). However, after the operation, all patients demonstrated improvements in cardiac function during exercise (delta LVEDP, positive; delta SVI, positive). Coronary sinus flow per left ventricular mass increased after operation from 70 +/- 46 to 87 +/- 56 ml/min at rest (p less than 0.05) and from 139 +/- 118 to 183 +/- 150 ml/min during exercise (p less than 0.05). CONCLUSIONS: In conclusion, this study reveals improvements in both hemodynamics and coronary blood flow during exercise after coronary artery bypass grafting with IMA grafts in pediatric patients with Kawasaki disease. PMID- 1860206 TI - Altered lipid profile after Kawasaki syndrome. AB - BACKGROUND: Delineation of lipid values in children after Kawasaki syndrome is important because of the predilection of this disease for the coronary arteries. METHODS AND RESULTS: We measured plasma concentrations of total cholesterol, high density lipoprotein (HDL) cholesterol, and triglycerides using enzymatic methods in 105 patients with a history of Kawasaki syndrome. Measurements were obtained during six time periods: 10 days or less, 11-31 days, 1-3 months, 3-12 months, 1 3 years, and more than 3 years. Total cholesterol was depressed in the first interval (122.0 +/- 19.8 mg/dl, mean +/- SD), but the mean values were normal in all periods after clinical recovery (overall mean, 149.0 +/- 24.0 mg/dl). High density lipoprotein cholesterol was also depressed in the first interval (15.2 +/ 9.9 mg/dl); although high density lipoprotein cholesterol increased significantly with duration since disease onset (p less than 0.001), it remained significantly lower than expected (p less than 0.001), even in the latest interval (47.2 +/- 10.9 mg/dl). Nonfasting triglyceride levels were high (162.5 +/- 63.4 mg/dl) in the first interval and then diminished steadily with time, but this relation did not achieve statistical significance. We compared adjusted lipid levels (z scores) of 46 Kawasaki patients after clinical recovery with those of their parents; patients had similar total cholesterol levels but significantly lower high density lipoprotein cholesterol levels (p = 0.021 for mothers, p = 0.001 for fathers). Mean high density lipoprotein cholesterol after clinical recovery tended to be lower in patients with persistent coronary abnormalities than in those without such lesions (p = 0.085). CONCLUSIONS: Kawasaki syndrome is associated with important abnormalities in lipid metabolism. Continued long-term surveillance of this population is necessary to monitor lipid levels and their relation to future development of coronary atherosclerosis. PMID- 1860207 TI - Percutaneous excimer laser coronary angioplasty of lesions not ideal for balloon angioplasty. AB - BACKGROUND: Excimer laser coronary angioplasty is a new, investigational technique for treating coronary artery stenoses. Initial reports have demonstrated acute efficacy and relative safety of this procedure, but have not addressed the effect of lesion type on acute success and complication rates. METHODS AND RESULTS: In the first 100 patients undergoing percutaneous excimer laser coronary angioplasty at our institution, acute laser success was obtained in 84% and procedural success was obtained in 94%. There were six acute closures during laser angioplasty and one myocardial infarction. Two patients required emergency coronary bypass surgery. Sixty-five percent of patients had lesions not ideal for balloon angioplasty because of lesion morphology (tubular, diffuse, or chronic total occlusion) or ostial location. There were 10 tubular stenoses, 29 diffuse lesions, 18 chronic total occlusions, and eight ostial lesions, including five aorto-ostial lesions. In this nonideal subgroup, the acute success rate with laser was 86% (72% of chronic total occlusions and 91% of non-totally occluded lesions), and the procedural success rate was 94%. There were three acute occlusions during laser angioplasty but no myocardial infarctions, emergency bypass surgeries, or deaths. One coronary artery perforation occurred without clinical sequelae. Laser angioplasty was successful in four of six lesions (67%) in which balloon angioplasty had failed. Laser success was obtained in 10 of 11 (91%) moderately or heavily calcified stenoses. Eight eccentric lesions and two lesions on bends were successfully treated without dissection or perforation. No side branch occlusions occurred in the 15 patients in whom one or more major branches originated within the lesion treated. Adjunctive balloon angioplasty was performed in 47% of cases, usually to obtain a larger final luminal diameter. Need for adjunctive balloon angioplasty decreased to 36% after a larger (2.0 mm) laser catheter became available. Twenty-eight percent of the 105 lesions treated were American College of Cardiology/American Heart Association classification type A, 47% were type B, and 25% were type C. Laser and procedural successes were obtained in 83% and 97% of type A, 88% and 96% of type B, and 85% and 88% of type C lesions, respectively. CONCLUSIONS: In our initial experience, excimer laser angioplasty was found to be acutely effective and safe therapy for lesions identified as not ideal for balloon angioplasty. This technique may provide a useful adjunct or alternative to balloon angioplasty in selected patients. PMID- 1860208 TI - Relation of stenosis morphology and clinical presentation to the procedural results of directional coronary atherectomy. AB - BACKGROUND: Directional coronary atherectomy has recently become available to treat coronary stenoses. This study was performed to determine the relation of patient characteristics and stenosis morphology to procedural outcome with directional coronary atherectomy to gain insight into which patients might be best treated with this device. METHODS AND RESULTS: Four hundred stenoses from 378 patients consecutively treated at six major referral institutions were analyzed. Angiographic data were assessed at a central angiographic laboratory using standardized morphological criteria and computer-assisted quantitative dimensional analyses. Procedural success was achieved in 87.8% of stenoses, and major ischemic complications (death, myocardial infarction, and emergency bypass surgery) occurred in 6.3% of patients. Lesion success and complications were closely correlated with recognized modified American College of Cardiology/American Heart Association Task Force lesion morphological criteria. Observed for type A stenoses were 93% success and 3% complication rates; for type B1 stenoses, 88% success and 6% complication rates; and for type B2 stenoses, 75% success and 13% complication rates, respectively. There were too few type C stenoses treated to analyze. Furthermore, multivariate testing demonstrated stenosis angulation (multivariate p less than 0.001), proximal tortuosity (p less than 0.001), decreased preatherectomy minimum lumen dimension (p = 0.032), and calcification (p = 0.041) to correlate independently with adverse outcome and complex, probably thrombus-associated stenoses to have a favorable outcome (p = 0.055). Operator experience (p = 0.020) and a history of restenosis (p = 0.022) also favorably influenced outcome. CONCLUSIONS: The procedural outcome of directional coronary atherectomy is highly associated with coronary stenosis morphology. Furthermore, after appropriate stratification for morphology and clinical presentation, overall atherectomy procedural outcome may be similar to that achieved with coronary angioplasty. However, specific subsets of patients may have relatively better outcome with either atherectomy or balloon angioplasty. PMID- 1860209 TI - Effects of aging, gender, and physical training on peripheral vascular function. AB - BACKGROUND: Blood pressure and total peripheral resistance increase with age. However, the effect of age on vasodilatory capacity has not been characterized. METHODS AND RESULTS: To delineate the effects of aging, gender, and physical training on peripheral vascular function, we measured blood pressure during submaximal and maximal treadmill exercise and measured blood pressure, calf blood flow, and calf conductance (blood flow/mean blood pressure) at rest and during maximal hyperemia in 58 healthy sedentary subjects (men aged 25 +/- 5 and 65 +/- 3 years and women aged 27 +/- 5 and 65 +/- 4 years) and in 52 endurance exercise trained subjects (men aged 30 +/- 3 and 65 +/- 4 years and women aged 27 +/- 3 and 65 +/- 3 years). Systolic and mean blood pressures were higher at rest, during maximal calf hyperemia, and during submaximal exercise of the same intensity in the older than in the younger subjects of the same gender and exercise training status (p less than 0.01). The magnitude of the age-related effect on blood pressure during exercise was greater in women than in men (p less than 0.01). Diastolic blood pressure during submaximal exercise was also higher in the older than in the younger subjects (p less than 0.05) but not in women treated with estrogen replacement. In contrast, systolic and mean blood pressures during submaximal work were lower in physically conditioned subjects than in sedentary age- and gender-matched subjects (p less than 0.05) but not in older women. Increased age was associated with reduced maximal calf conductance in women (p less than 0.01) but not in men. However, calf vasodilatory capacity was higher in trained than in untrained subjects (p less than 0.01), regardless of age and gender. There was a significant inverse relation between maximal calf conductance and systolic, diastolic, and mean blood pressures during submaximal exercise (r = -0.31 to -0.53, p less than 0.01) and a direct relation between maximal calf conductance and maximal oxygen uptake (r = 0.66, p less than 0.0001). CONCLUSIONS: Thus, for healthy subjects between the ages of 25 and 65 years, there is an interactive effect between age and gender and an independent effect of physical training on peripheral vascular function. PMID- 1860210 TI - Electrode system influence on biphasic waveform defibrillation efficacy in humans. AB - BACKGROUND: Several clinical studies have demonstrated a general superiority of biphasic waveform defibrillation compared with monophasic waveform defibrillation using epicardial lead systems. To test the breadth of utility of biphasic waveforms in humans, a prospective, randomized evaluation of defibrillation efficacy of monophasic and single capacitor biphasic waveform pulses was performed for two distinct nonthoracotomy lead systems as well as for an epicardial electrode system in 51 cardiac arrest survivors undergoing automatic defibrillator implantation. METHODS AND RESULTS: The configurations tested consisted of a right ventricular-left ventricular (RV-LV) epicardial patch-patch system, an RV catheter-chest patch (CP) nonthoracotomy system, and a coronary sinus (CS) catheter-RV catheter nonthoracotomy system. For each configuration, the defibrillation current and voltage waveforms were recorded via a digital oscilloscope to measure defibrillation threshold voltage, current, resistance, and stored energy. Biphasic waveform defibrillation proved more efficient than monophasic waveform defibrillation for the epicardial RV-LV system (4.8 +/- 4.1 versus 6.7 +/- 4.9 J, p = 0.047) and the nonthoracotomy RV-CP system (23.4 +/- 11.1 versus 34.3 +/- 10.4 J, p = 0.0042). Biphasic waveform defibrillation thresholds were not significantly lower than monophasic waveform defibrillation thresholds for the CS-RV nonthoracotomy system (15.6 +/- 7.2 versus 20.0 +/- 11.5 J, p = 0.11). Biphasic waveform defibrillation proved more efficacious than monophasic waveform defibrillation in 13 of 20 patients (65%) with RV-LV epicardial patches, 10 of 15 patients (67%) with an RV-CP nonthoracotomy system, and nine of 16 patients (56%) with an RV-CS nonthoracotomy system. CONCLUSIONS: Biphasic pulsing was useful with nonthoracotomy lead systems as well as with epicardial lead systems. However, the degree of biphasic waveform defibrillation superiority appeared to be electrode system dependent. Furthermore, for a few individuals, biphasic waveform defibrillation proved less efficient than monophasic waveform defibrillation, regardless of the lead system used. PMID- 1860211 TI - Differences in electrophysiological substrate in patients with coronary artery disease and cardiac arrest or ventricular tachycardia. Insights from endocardial mapping and signal-averaged electrocardiography. AB - BACKGROUND: Many studies have combined patients with hemodynamically well tolerated ventricular tachycardia (VT) and those with cardiac arrest (CA) as a single, homogenous group. Recent studies suggest that these two groups have different electrophysiological substrates and responses to therapy. Most of these studies, however, enrolled patients with a variety of cardiac diagnoses. METHODS AND RESULTS: We used signal-averaged electrocardiography (SAECG) and endocardial catheter mapping to define the electrophysiological substrate in patients with coronary artery disease and VT or CA and correlate the results of the two methods. We also examined the usefulness of SAECG in CA patients to differentiate those with inducible arrhythmias from those who are noninducible. VT patients were more likely to have had a prior myocardial infarction (p = 0.0005) and to have inducible arrhythmias (p = 0.0001) than were CA patients. The induced arrhythmias in patients who presented with VT was VT in more than 90% of cases, whereas in CA patients, polymorphic ventricular tachycardia (PMVT) accounted for one third of induced arrhythmias. Mean filtered QRS duration was longer (135 versus 120 msec) and the terminal QRS voltage was smaller (20 versus 34 microV) in VT than in CA patients (p less than 0.01). Sixty-three percent of CA patients and 87% of VT patients had abnormal SAECG (p = 0.001). VT patients had more extensive endocardial abnormalities and more abnormal (53% versus 40%, p = 0.002), fractionated (8% versus 3%, p = 0.02), late (17% versus 8%, p = 0.0003), and late abnormal or fractionated (14% versus 4%, p = 0.0001) sites than CA patients. VT patients had a greater duration of the longest electrogram (129 versus 109 msec, p = 0.0006) and total endocardial activation time (68 versus 54 msec, p = 0.009). Among CA patients, those with induced VT had more extensive substrate than did those with induced PMVT and were similar to VT patients with induced VT. Among CA patients, the trend for more patients with inducible VT (77%) or PMVT (55%) than noninducible patients (47%) to have an abnormal SAECG did not reach statistical significance (p = 0.14). The positive and negative predictive values of an abnormal SAECG were 77% and 44%, respectively. CONCLUSIONS: VT patients have more extensive endocardial substrate than CA patients, which translates into greater and more frequent SAECG abnormalities. Among CA patients, there are significant differences in substrate between patients with induced VT and those with induced PMVT. SAECG is not useful in differentiating CA patients who have inducible VT or PMVT from those who do not. PMID- 1860212 TI - Suppression of eicosanoid biosynthesis during coronary angioplasty by fish oil and aspirin. AB - BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is an acute, localized stimulus to platelet and vascular function. Periprocedural cardiovascular complications are reduced by moderate-dose aspirin (ASA), presumably due to inhibition of thromboxane (TX) A2. METHODS AND RESULTS: Excretion of TXA2 and prostacyclin (PGI2) metabolites in urine increased during PTCA. Pretreatment for 3 days with either moderate- (325 mg/day) or low-dose (80 mg/day) ASA inhibited the increase in both eicosanoids. Pretreatment for 3 weeks with fish oil (10 g/day) only partially suppressed TXA2. Formation of trienoic eicosanoids and accumulation of omega-3 fatty acids in platelet membranes confirmed fish oil ingestion. Although basal PGI2 was not inhibited, the PTCA related increment was suppressed. CONCLUSIONS: PTCA results in an acute, transient alteration of eicosanoid biosynthesis consistent with accelerated platelet-vascular interactions. Pretreatment for 3 days with moderate or low doses of ASA suppresses TXA to a similar extent during PTCA, and their effects on acute cardiovascular complications of this procedure are likely to be comparable. It is unlikely that even prolonged pretreatment with fish oil can substitute for the platelet inhibitory action of ASA during PTCA. Suppression of PGI2 may contribute to the residual acute periprocedural complication rate in patients taking ASA. PMID- 1860213 TI - Abnormal vascular responses to supine exercise in hypertrophic cardiomyopathy. AB - BACKGROUND: Exercise hypotension has been documented in hypertrophic cardiomyopathy. It is not the result of an inability to augment cardiac output but instead relates to an inappropriate and exaggerated decrease in systemic vascular resistance at high work loads. METHODS AND RESULTS: To enable us to examine the behavior of the peripheral vasculature during exercise, 103 consecutive patients underwent maximal symptom-limited supine bicycle exercise with measurement of forearm blood flow. A minimum reduction of 12% from the basal value was defined as a normal response based on the study of 25 normal controls. In the patients, two patterns of forearm blood flow were observed. Sixty-four patients had an appropriate reduction in forearm blood flow of 40 +/- 16% from resting flow. In 39 patients, the forearm blood flow either failed to decrease or increased with exercise by 45 +/- 105% of the resting value. Patients with an abnormal forearm vasodilator response were younger (31 +/- 13 versus 46 +/- 14 years), and more of them had a family history of hypertrophic cardiomyopathy and sudden death than did those with a normal vasoconstrictor response (16 of 39 versus eight of 64). Left ventricular end-diastolic cavity dimensions were smaller in those with an abnormal forearm blood flow response, but other clinical, echocardiographic, and arrhythmic variables were similar. To assess the relation of abnormal peripheral vascular responses to erect exercise blood pressure response, patients underwent treadmill exercise testing with careful monitoring of systolic blood pressure response. Thirty-eight patients had significant exercise hypotension with failure of the systolic blood pressure to increase during progressive exercise (n = 6) or an abrupt decrease in systolic blood pressure (20-60 mm Hg) from the peak value (n = 32); 65 patients had a normal exercise blood pressure response, but 18 of these patients had an oscillation in systolic blood pressure of 10 mm Hg or more early in the recovery phase. Thirty-one of 39 patients with an abnormal forearm blood flow response demonstrated exercise hypotension during the erect exercise testing, and the remaining eight patients had a normal exercise blood pressure response; however, five of these eight had abnormal oscillations in blood pressure during recovery (r = 0.61, p less than 0.001). CONCLUSIONS: The relation of abnormal peripheral vascular responses to exercise hypotension confirms the observation of hemodynamic instability in patients with hypertrophic cardiomyopathy. The finding of abnormal vascular responses in patients known to be at increased risk (young age and a family history of hypertrophic cardiomyopathy and sudden death) suggests that hemodynamic mechanisms may be important in the occurrence of sudden death in hypertrophic cardiomyopathy. PMID- 1860214 TI - Diminishment of respiratory sinus arrhythmia foreshadows doxorubicin-induced cardiomyopathy. AB - BACKGROUND: The development of a microcomputer-based device permits quick, simple, and noninvasive quantification of the respiratory sinus arrhythmia (RSA) during quiet breathing. METHODS AND RESULTS: We prospectively and serially measured the radionuclide left ventricular ejection fraction and the RSA amplitude in 34 cancer patients receiving up to nine monthly bolus treatments with doxorubicin hydrochloride (60 mg/m2). Of the eight patients who ultimately developed symptomatic doxorubicin-induced congestive heart failure, seven (87.5%) demonstrated a significant decline in RSA amplitude; five of 26 subjects without clinical symptoms of cardiotoxicity (19.2%) showed a similar RSA amplitude decline. On average, significant RSA amplitude decline occurred 3 months before the last planned doxorubicin dose in patients destined to develop clinical congestive heart failure. CONCLUSION: Overall, RSA amplitude abnormality proved to be a more specific predictor of clinically significant congestive heart failure than did serial resting radionuclide ejection fractions. PMID- 1860215 TI - Clinical characteristics of nonfatal myocardial infarction among individuals on prophylactic low-dose aspirin therapy. AB - BACKGROUND: The influence of prophylactic low-dose aspirin on the clinical characteristics of subsequent nonfatal myocardial infarction was examined in the Physicians' Health Study, a randomized, double-blind placebo-controlled trial of alternate-day aspirin (325 mg) among 22,071 US male physicians. METHODS AND RESULTS: During 60.2 months of follow-up, 342 incident cases of nonfatal myocardial infarction were confirmed (95.2% of all reports): 129 on aspirin and 213 on placebo (p less than 0.00001). Despite this statistically extreme reduction in occurrence of a first nonfatal infarction attributable to aspirin, there were no significant differences in the size, location, electrocardiographic features, or postinfarction left ventricular ejection fraction between the aspirin and placebo groups. Furthermore, among those undergoing angiography, there were no differences in the distribution or number of coronary vessels obstructed. CONCLUSIONS: These data indicate that chronic platelet inhibition with alternate-day aspirin therapy reduces the risk of a first myocardial infarction but does not appear to have a significant effect on the clinical characteristics of events that are survived. This finding may result from a direct effect of aspirin or from an aspirin-induced shift in infarction severity. Regardless of mechanism, these clinical observations suggest that treatment decisions for acute infarction patients should be made independently of a history of aspirin use. PMID- 1860216 TI - Impact of impinging wall jet on color Doppler quantification of mitral regurgitation. AB - BACKGROUND: In clinical color Doppler examinations, mitral regurgitant jets are often observed to impinge on the left atrial wall immediately beyond the mitral valve. In accordance with fluid dynamics theory, we hypothesized that a jet impinging on a wall would lose momentum more rapidly, undergo spatial distortion, and thus have a different observed jet area from that of a free jet with an identical flow rate. METHODS AND RESULTS: To test this hypothesis in vivo, we studied 44 patients with mitral regurgitation--30 with centrally directed free jets and 14 with eccentrically directed impinging wall jets. Maximal color jet areas (cm2) (with and without correction for left atrial size) were correlated with mitral regurgitant volumes, flow rates, and fractions derived from pulsed Doppler mitral and aortic forward flows. The groups were compared by analysis of covariance. Mean +/- SD mitral regurgitant fraction, regurgitant volume, and mean flow rate averaged 37 +/- 17%, 3.06 +/- 2.65 l/min, and 147 +/- 118 ml/sec, respectively. The maximal jet area from color Doppler imaging correlated relatively well with the mitral regurgitant fraction in the patients with free mitral regurgitant jets (r = 0.74, p less than 0.0001) but poorly in the patients with impinging wall jets (r = 0.42, p = NS). Although the mitral regurgitant fraction was larger (p less than 0.05) in patients with wall jets (44 +/- 20%) than in those with free jets (33 +/- 15%), the maximal jet area was significantly smaller (4.78 +/- 2.87 cm2 for wall jets versus 9.17 +/- 6.45 cm2 for free jets, p less than 0.01). For the same regurgitant fraction, wall jets were only approximately 40% of the size of a corresponding free jet, a difference confirmed by analysis of covariance (p less than 0.0001). CONCLUSIONS: Patients with mitral regurgitation frequently have jets that impinge on the left atrial wall close to the mitral valve. Such impinging wall jets are less predictable and usually have much smaller color Doppler areas in conventional echocardiographic views than do free jets of similar regurgitant severity. Jet morphology should be considered in the semiquantitative interpretation of mitral regurgitation by Doppler color flow mapping. Future studies of the three-dimensional morphology of wall jets may aid in their assessment. PMID- 1860217 TI - Quantification of and correction for left ventricular systolic long-axis shortening by magnetic resonance tissue tagging and slice isolation. AB - BACKGROUND: Measurement of regional left ventricular (LV) function is predicted on the ability to compare equivalent LV segments at different time points during the cardiac cycle. Standard techniques of short-axis acquisition in two dimensional echocardiography, cine computed tomography, and standard magnetic resonance imaging (MRI) acquire images from a fixed plane and fail to compensate for through-plane motion. The shortening of the left ventricle along its long axis during systole results in planar images of two different levels of the ventricle, leading to error in any derived functional measurements. LV systolic long-axis motion was measured in 19 normal volunteers using MRI. METHODS AND RESULTS: With a selective radio frequency (RF) tissue-tagging technique, three short-axis planes were labeled at end diastole and standard spin-echo images were acquired at end systole in the two- and four-chamber orientations. Persistence of the tags through systole allowed visualization of the intersecting short-axis tags in the long-axis images and allowed precise quantification of long-axis motion of the septum, lateral, anterior, and inferior walls at the base, mid, and apical LV levels. The total change in position along the long axis between end diastole and end systole was greatest at the base, which moved toward the apex 12.8 +/- 3.8 mm. The mid left ventricle moved 6.9 +/- 2.6 mm, and the apex was nearly stationary, moving only 1.6 +/- 2.2 mm (p less than 0.001). Having quantified the normal range of long-axis shortening, we developed a technique that isolates a slice of tissue between selective RF saturation planes at end diastole. Combining this with a wide end-systolic image slice, end-systolic images were acquired without contamination of signal from adjacent tissue moving into the imaging plane. This technique was validated in a moving phantom and in normal volunteers. CONCLUSIONS: Significant LV systolic long-axis shortening exists, and this effect is seen the most at the base and the least at the apex. At a given ventricular level, shortening varied significantly according to location. A method using selective saturation pulses and gated spin-echo MRI automatically corrects for this motion and thus eliminates misregistration artifact from regional function analysis. PMID- 1860218 TI - Intermediate-term effectiveness of balloon valvuloplasty for congenital aortic stenosis. A prospective follow-up study. AB - BACKGROUND: Percutaneous balloon valvuloplasty has proven to be acutely effective in the treatment of congenital valvar aortic stenosis; however, the intermediate- and long-term effectiveness of the procedure remain to be documented. METHODS AND RESULTS: To assess the intermediate-term effectiveness of balloon valvuloplasty, repeat catheterization was performed in 27 of 30 children 1.7 +/- 0.1 years after balloon valvuloplasty for congenital aortic stenosis (AS). In 33 children the peak AS gradient was reduced acutely by 55% from 77 +/- 4 to 35 +/- 3 mm Hg (p less than 0.001), and left ventricular systolic pressure was reduced from 176 +/- 4 to 138 +/- 4 mm Hg (p less than 0.001). Despite a technically adequate valvuloplasty procedure, three patients had inadequate relief of obstruction and required complex surgical intervention. Twenty-seven of the 30 patients available for late reevaluation (90%) enrolled in the follow-up study. The peak AS gradient remained significantly reduced compared with that present before valvuloplasty (29 +/- 3 versus 77 +/- 4 mm Hg, p less than 0.001). Furthermore, there was no difference in peak AS gradient at follow-up compared with that immediately after valvuloplasty. The greatest increase in gradient at reevaluation was 14 mm Hg. Twenty of 27 patients (74%) had no change in the degree of aortic insufficiency at follow-up compared with that present before valvuloplasty. At follow-up, 16 patients had no aortic insufficiency at all, and only two had moderate-to-severe (3-4+) insufficiency. Femoral artery injury was documented in four patients, three of whom were under 12 months of age at valvuloplasty. CONCLUSIONS: Balloon aortic valvuloplasty provides safe and effective intermediate-term gradient relief without early restenosis in children and adolescents with congenital AS. PMID- 1860219 TI - Combination balloon-ultrasound imaging catheter for percutaneous transluminal angioplasty. Validation of imaging, analysis of recoil, and identification of plaque fracture. AB - BACKGROUND: We investigated the hypothesis that an ultrasound transducer positioned within an angioplasty balloon could be used to perform quantitative assessment of arterial dimensions before and after percutaneous transluminal angioplasty (PTA) and to identify certain mechanical alterations consequent to PTA, including vascular wall recoil and the initiation of plaque fractures. METHODS AND RESULTS: A combination balloon-ultrasound imaging catheter (BUIC) that houses a 20-MHz ultrasound transducer within and halfway between the proximal and distal ends of an angioplasty balloon was used to perform PTA in 10 patients with peripheral vascular disease. Each PTA site was also evaluated before and after PTA by standard (nonballoon) intravascular ultrasound (IVUS) technique. In eight patients in whom satisfactory images were recorded with the BUIC before PTA, luminal cross-sectional area (XSA) of stenotic sites (0.10 +/- 0.01 cm2) did not differ significantly from measurements of XSA by IVUS (0.09 +/- 0.01 cm2, p = NS). Likewise, minimum luminal diameter (Dmin) measured by BUIC (0.34 +/- 0.02 cm) was similar to that measured by IVUS (0.33 +/- 0.01 cm, p = NS). In nine patients in whom satisfactory images were recorded with the BUIC after PTA, XSA measured by BUIC (0.29 +/- 0.03 cm2) did not differ significantly from XSA measured by IVUS (0.30 +/- 0.03 cm2, p = NS). Dmin measured by BUIC after PTA (0.57 +/- 0.02 cm) was also similar to Dmin measured by IVUS (0.57 +/- 0.03 cm, p = NS). After PTA, XSA and Dmin measured immediately after deflation were significantly less than balloon XSA and diameter at full inflation, indicating significant elastic recoil of the dilated site. For the nine patients in whom post-PTA images were satisfactory for quantitative analysis, including four patients in whom recoil was 39%, 46%, 50%, and 61%, percent recoil measured 28.6 +/- 7.2%. Finally, plaque fractures were identified on-line in six of 10 patients (60%); in each case, initiation of plaque fracture was observed at inflation pressures of 2 atm or less. CONCLUSIONS: The results of this preliminary human investigation indicate that an ultrasound transducer positioned within an angioplasty balloon can be used to perform quantitative and qualitative analyses of lumen-plaque-wall alterations immediately preceding, during, and immediately after PTA in patients with peripheral vascular disease. PMID- 1860220 TI - Differences in the effect of metabolic inhibition on action potentials and calcium currents in endocardial and epicardial cells. AB - BACKGROUND: Ischemia-induced electrophysiological changes are more prominent in epicardial cells than in endocardial cells. Epicardial action potentials shorten more than endocardial action potentials during ischemia. Since the L-type Ca2+ current plays an important role in the maintenance of action potential duration, we hypothesized that the Ca2+ current is affected more in epicardial cells than in endocardial cells during ischemia. METHODS AND RESULTS: To test this hypothesis, we examined the effect of metabolic inhibition, a major component of ischemia, on action potentials and the Ca2+ current in single cells isolated from the endocardial and epicardial layers of the feline left ventricle. The membrane voltage and current were measured by using the whole-cell mode of the patch-clamp technique. During control periods, action potentials recorded from epicardial myocytes had lower amplitude, a prominent notch between phases 1 and 2, and shorter action potential duration compared with those recorded from endocardial myocytes. However, the amplitude and current-voltage relation of the Ca2+ current were similar in endocardial and epicardial cells at test potentials of -30 to 60 mV elicited from a holding potential of -40 mV. The time course of inactivation of the Ca2+ current also was identical in the two cell types. After 15 minutes of superfusion with glucose-free Tyrode's solution containing 1 mM CN-, action potential duration was reduced by 13 +/- 7% in endocardial cells and by 80 +/- 9% in epicardial cells (p less than 0.01). The peak Ca2+ current was reduced by 21 +/- 9% in endocardial cells and by 37 +/- 6% in epicardial cells (p less than 0.01). CONCLUSIONS: We conclude that enhanced depression of the Ca2+ current may account in part for the greater action potential shortening in epicardial cells during ischemia and metabolic inhibition. PMID- 1860221 TI - Cytotoxic effects of a recombinant chimeric toxin on rapidly proliferating vascular smooth muscle cells. AB - BACKGROUND: Restenosis after percutaneous transluminal coronary angioplasty is associated with activation of medial smooth muscle cells (SMCs); they proliferate, migrate to the subintima, and narrow the vessel lumen. Cancer cells often express more cell surface receptors than do normal cells. This has allowed tumor cells to be specifically targeted using cytotoxic agents. We have examined whether a similar concept can be applied to rapidly proliferating but nontransformed SMCs. Pseudomonas exotoxin (PE; MW, 66 kDa) is a potent toxin that kills cells by inhibiting protein synthesis; its toxicity is diminished when its cell recognition domain is deleted to produce a 40-kDa protein (PE40). METHODS AND RESULTS: A complementary DNA encoding transforming growth factor alpha (TGF alpha) was ligated to that encoding PE40 and the chimeric toxin TGF alpha-PE40, which is cytotoxic to cancer cells displaying epidermal growth factor (EGF) receptors, was expressed in Escherichia coli. The ability of this toxin to kill proliferating SMCs was tested. When cells were seeded at low density (2,500 cells/cm2) and grown in medium supplemented with 10% fetal bovine serum, they were found to be rapidly proliferating; these cells were very sensitive to the cytotoxic effects of TGF alpha-PE40 (ID50, 4.0 +/- 0.17 ng/ml). In contrast, cytotoxicity was 30-fold less (ID50, 125 +/- 23 ng/ml; p less than 0.0004) when cells were in a quiescent state (grown in medium supplemented with 0.5% fetal bovine serum). CONCLUSIONS: Competition studies using excess EGF indicated that the cytotoxic effects of TGF alpha-PE40 are specifically mediated by the EGF receptor. EGF receptor binding analysis demonstrated that rapidly proliferating SMCs display 10-fold more EGF receptors than do quiescent SMCs in vitro. Thus, a chimeric toxin targeted toward the EGF receptor can selectively kill rapidly proliferating SMCs. Whether this toxin or other chimeric toxins directed against other cell surface receptors will effectively inhibit SMCs proliferating in vivo or be useful in preventing restenosis remains to be determined. PMID- 1860222 TI - Effects of milrinone on left ventricular remodeling after acute myocardial infarction. AB - BACKGROUND: Left ventricular remodeling after an acute myocardial infarction may result in progressive left ventricular dilation that may be associated with increased mortality. We studied the effects of the phosphodiesterase inhibitor milrinone on left ventricular remodeling after acute myocardial infarction. METHODS AND RESULTS: Rats (n = 90) were randomized to undergo either left coronary artery ligation or sham operation. Three weeks after surgery, rats received either no treatment or milrinone, which was continued until 2 days before the rats were killed. Ninety days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically. Compared with untreated infarcted rats, milrinone-treated infarcted rats had a lower left ventricular end-diastolic pressure (1.7 +/- 0.4 versus 4.3 +/- 1.4 mm Hg, p less than 0.05), a lower left ventricular volume (1.25 +/- 0.20 versus 2.37 +/- 0.30 ml/kg, p less than 0.001) and a lower left ventricular wall stress index (1.3 +/- 0.2 versus 1.7 +/- 0.1, p less than 0.05). Left ventricular chamber stiffness was higher in milrinone-treated infarcted rats than in untreated infarcted rats. Milrinone had no cardiac effect on uninfarcted animals. CONCLUSION: Chronic milrinone therapy after acute myocardial infarction improves cardiac hemodynamic indexes and attenuates progressive left ventricular dilation. PMID- 1860223 TI - Platelet-targeted fibrinolysis enhances clot lysis and inhibits platelet aggregation. AB - BACKGROUND: Although plasminogen activator therapy has been shown to reduce mortality in patients with severe myocardial infarction, several problems fuel the search for more potent and specific thrombolytic agents. METHODS AND RESULTS: To explore the effect of plasminogen activator targeting to platelets, we covalently linked urokinase that had been modified with N-succinimidyl-3-(2 pyridyldithio)propionate to the Fab' of a monoclonal antibody (7E3) that selectively binds to platelet membrane glycoprotein (GP) IIb/IIIa. In an assay measuring (as reflected by plasmin generation) a plasminogen activator's ability to bind GP IIb/IIIa immobilized on plastic, urokinase-7E3 Fab' produced 31-fold more plasmin than did urokinase (p = 0.0001). The addition of solubilized GP IIb/IIIa blocked this enhancement of plasmin generation, indicating that binding was impaired. Plasmin generation reflecting binding to immobilized intact platelets was 2.4-fold greater for urokinase-7E3 Fab' than for unconjugated urokinase (p = 0.002). In a plasma clot lysis assay, urokinase-7E3 Fab' was at least 25-fold more potent than either urokinase alone or a mixture of urokinase and 7E3 (Fab')2 (p less than 0.009), and potency could be related to platelet concentration in the clot. Ex vivo, ADP-induced platelet aggregation was inhibited by a urokinase-7E3 IgG conjugate at a concentration of 8 nM, whereas a mixture of urokinase and 7E3 (Fab')2 in equimolar amounts required 60 nM and urokinase alone required 1 microM to achieve the same effect. CONCLUSIONS: Therefore, the targeting of urokinase to the GP IIb/IIIa platelet receptor both accelerates clot lysis (when platelets are associated with a fibrin clot) and inhibits platelet aggregation. PMID- 1860224 TI - Prevention of arterial reocclusion after thrombolysis with recombinant lipoprotein-associated coagulation inhibitor. AB - BACKGROUND: This study was designed to determine whether arterial reocclusion after thrombolysis can be prevented by lipoprotein-associated coagulation inhibitor (LACI), a physiological inhibitor of tissue factor-induced coagulation mediated by the extrinsic pathway. METHODS AND RESULTS: Thrombosis was induced in femoral arteries of anesthetized dogs with the use of anodal current to elicit extensive vascular injury and formation of platelet-rich thrombi in one artery and with thrombogenic copper wire to elicit fibrin-rich thrombi without appreciable vascular injury in the contralateral artery. Recanalization of both vessels was induced with t-PA (1.7 mg/kg i.v. over 1 hour) and verified with Doppler flow probes. Reocclusion occurred within 2 hours in seven of seven arteries with electrical injury-induced thrombosis and in four of seven arteries with copper wire-induced thrombosis in the absence of LACI. In dogs given infusions of recombinant DNA-produced LACI (225 micrograms/kg over 15 minutes, followed by 4 micrograms/kg/min i.v.) after completion of the infusion of t-PA, no reocclusion occurred during the 2-hour interval of observation in any of the five arteries subjected to electrical injury (p less than 0.001), and cyclic partial occlusions were nearly abolished (0.4 +/- 0.4/hr in LACI-treated dogs compared with 13.7 +/- 5.5/hr in saline-treated dogs, p less than 0.0001). In contrast, reocclusion occurred in two of five arteries with indwelling copper wires, and cyclic partial occlusions were unaffected despite LACI. LACI prolonged the partial thromboplastin time modestly (1.7 +/- 0.2 x baseline) but did not affect platelet counts or aggregation assessed ex vivo. CONCLUSIONS: Inhibition of the extrinsic pathway of coagulation with LACI prevents thrombotic arterial reocclusion after thrombolysis in vessels subjected to extensive vascular injury. Our results demonstrate that activation of the extrinsic pathway plays a critical role in thrombotic reocclusion and that LACI provides a highly targeted approach to facilitate sustained recanalization without directly inhibiting platelets. PMID- 1860226 TI - Anatomy of the tricuspid annulus. Circumferential myofibers as the structural basis for atrial flutter in a canine model. AB - BACKGROUND: Little anatomic information is available on the annular myocardium. This study was conducted to determine the anatomic substrate for atrial flutter due to circus movement around the tricuspid annulus in the Y-shaped incision canine model of atrial flutter. METHODS AND RESULTS: We studied photographs of the annular myocardium serial histological sections, made in either of three different planes, and compared these with photographs of the intact and blocked gross heart specimens. We found that the annulus is the most caudal region of the atrial wall. The epicardial aspect of the annulus abuts the ventricular septum or the aortic root in the medial region; in other regions, it is covered by the fat of the coronary sulcus. Its endocardial aspect is delimited by the tricuspid leaflets inferiorly and by the pectinate muscle bundles superiorly, except in the medial region where the pectinate muscle bundles are absent. The annular myocardium is bilaminated. A continuous subepicardial circumferential lamina is the most prominent and is robust in the anterior, lateral, and posterior regions, but it attenuates to a fine muscular connection in the medial region. Myofibers of its superior border merge with the pectinate muscle bundles or are admixed in the medial region with myocardium at the base of the medial atrial wall. Its inferior border makes little contact with the annulus fibrosus about the ring; however, in the medial region, these myofibers insert into fibrous tissue superior to the septal leaflet. A discontinuous, subendocardial perpendicular lamina contains myofibers that descend from the atrium; most of these myofibers insert into the annulus fibrosus about the ring, but the lamina is absent in the anteromedial region. CONCLUSIONS: We conclude that the continuous circumferential lamina provides the anatomic substrate for circus movement of excitation in this model. PMID- 1860225 TI - Role of oxygen-derived free radicals in myocardial edema and ischemia in coronary microvascular embolization. AB - BACKGROUND: Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization. METHODS AND RESULTS: To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization. CONCLUSIONS: We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization. PMID- 1860227 TI - Instantaneous hyperemic flow-versus-pressure slope index. Microsphere validation of an alternative to measures of coronary reserve. AB - BACKGROUND: The instantaneous hyperemic flow-versus-pressure (i-HFVP) slope index is a new method of assessing maximal coronary conductance and can be used as an alternative to conventional measures of coronary reserve. The i-HFVP slope index is determined by measuring the slope of the linear diastolic segment of the relation between instantaneous aortic pressure and hyperemic coronary flow. METHODS AND RESULTS: To validate the i-HFVP slope index as a measure of maximal coronary conductance, we compared this method with a microsphere-derived measurement of maximal coronary conductance (m-HFVP slope index) by determining the slope of the least-squares regression line of the data points for coronary flow during maximal hyperemia and four or five steady-state alterations of aortic pressure in 43 dogs (open-chest, anesthetized preparations) with or without coronary stenoses. The i-HFVP slope index demonstrated no dependence on heart rate, left ventricular end-diastolic pressure, or mean aortic pressure and was highly reproducible within the groups studied (intraclass correlation coefficient, 0.86 for normal arteries, 0.87 for stenotic arteries, and 0.93 for combined groups; for all coefficients, p less than 0.001). The i-HFVP slope index was significantly decreased in the presence of a stenosis (10.3 +/- 3.9 for normal arteries versus 3.6 +/- 1.6 for stenotic arteries, p less than 0.001) as was the transmural m-HFVP slope index (8.9 +/- 4.6 for normal arteries versus 5.3 +/- 3.1, p less than 0.01). Of special importance, the i-HFVP slope index measurement for normal arteries was not significantly different from the transmural and subendocardial m-HFVP slope index measurements (10.3 +/- 3.9 versus 8.9 +/- 4.6 and 9.2 +/- 5.7, respectively). For stenotic arteries, the i HFVP slope index measurement was also not significantly different from the transmural and subendocardial m-HFVP slope index measurements (3.6 +/- 1.6 versus 5.3 +/- 3.1 and 4.1 +/- 2.3, respectively). The i-HFVP slope index correlated best with subendocardial m-HFVP slope index measurements (correlation coefficient, 0.57; p less than 0.001). When the 95% confidence intervals for the transmural (or subendocardial) m-HFVP slope index in normal arteries were compared with the i-HFVP slope index values, the latter demonstrated a systematic trend to overestimate the m-HFVP slope index. In the presence of a stenosis, this effect was minimized, and the slope values were nearly identical. CONCLUSIONS: The i-HFVP slope index correlates most closely with subendocardial coronary conductance; the index is a hemodynamically independent measure of coronary reserve that is reproducible over a broad range of aortic pressures; and the methodology is applicable to an intact circulation in experimental preparations and may with future developments also prove useful in humans. PMID- 1860228 TI - Detection and localization of prolonged epicardial electrograms with 64-lead body surface signal-averaged electrocardiography. AB - BACKGROUND: Prolonged, fractionated ventricular electrograms often are detectable after myocardial infarction and are a marker for an arrhythmia-prone state. QRS late potentials detected on the body surface with signal-averaged electrocardiography (SAECG) are thought to arise from the diseased tissue that generates prolonged ventricular electrograms and as such are also a marker for arrhythmias. A limitation of the current SAECG technique is that recordings are obtained from only three bipolar lead pairs. Because late potentials probably arise from multiple small sources in the heart, more extensive sampling of the body surface may contribute additional information to the SAECG: The present study investigates the additional sensitivity of SAECG using 64 body surface leads in detecting prolonged epicardial electrograms and examines its use in determining the epicardial location of prolonged electrograms. METHODS AND RESULTS: Dogs were studied before and 5-10 days after either lateral left ventricular (n = 13) or right ventricular (n = 8) myocardial infarction. Greater prolongation of signal-averaged QRS duration was detected with 64-lead SAECG (postinfarction QRS duration, 100.3 +/- 16.3 msec) than with three-lead SAECG (postinfarction QRS duration, 89.4 +/- 10.1, p = 0.0005). Nineteen of the 21 dogs (90%) had prolonged epicardial electrograms detected over the infarct. The correlation between epicardial electrogram duration and signal-averaged QRS duration calculated from individual leads was much better for 64-lead SAECG (r = 0.88, p less than 0.0001) than for three-lead SAECG (r = 0.53, p = 0.01), and the difference was most marked in cases with longer electrogram durations (more than 100 msec). Local late potential maxima on the thorax after lateral left ventricular infarction were located to the left and inferior compared with those after right ventricular infarction (p = 0.006). CONCLUSIONS: SAECG with more extensive recording from the body surface using 64 leads detects greater QRS prolongation than three-lead SAECG, and the longer QRS durations detected correspond to the duration of prolonged epicardial electrograms. Body surface location of late potentials corresponds to the epicardial location of the prolonged electrograms. This application of body surface mapping techniques to SAECG may permit more sensitive detection of arrhythmia-prone states and may aid in identifying arrhythmia sources. PMID- 1860229 TI - Effects of vascular runoff on myointimal hyperplasia after mechanical balloon or thermal laser arterial injury in dogs. AB - BACKGROUND: Clinical evidence suggests that poor vascular runoff reduces the long term success rate of femoral angioplasty procedures. The purpose of this experimental study was to examine myointimal hyperplasia of dog femoral arteries after balloon denudation, thermal laser arterial injury, or sham operation in normal and reduced vascular runoff conditions. METHODS AND RESULTS: Before mechanical balloon injury or transluminal heated laser probe motion, the peripheral vascular runoff of dogs was reduced by ligating the femoral artery below its three distal side branches, decreasing the femoral flow rate from 114 +/- 9 to 52 +/- 5 ml/min (mean +/- SEM). Endothelial denudation with a predominantly intact elastic internal membrane and circumferential structural changes in the media were noted by light microscopy 1 hour after balloon injury. Focal completely necrotic lesions of intima and media were found 1 hour after thermal laser arterial injury. After 8 weeks, the maximal thickness of neointima plus media of the site of previous intervention was greater after balloon injury (0.45 +/- 0.03 mm) and thermal laser injury (0.54 +/- 0.03 mm) than after sham operation (0.40 +/- 0.01 mm; p less than 0.001) in normal runoff dogs. Reduced vascular runoff augmented myointimal hyperplasia both in the balloon-injured and thermally damaged arteries; the wall thickness increased from 0.45 +/- 0.03 to 0.93 +/- 0.10 mm and from 0.54 +/- 0.03 to 0.65 +/- 0.05 mm, respectively (p less than 0.001). The neointimal and medial wall area of the balloon-injured arteries contributed 48% to the area encompassed by the external elastic membrane compared with an 81% portion when vascular runoff was reduced (p less than 0.01). A 47% neointimal and medial wall area was found in thermally injured arteries with normal runoff compared with 63% after runoff reduction (p less than 0.05). CONCLUSION: This study suggests that hemodynamic factors associated with poor vascular runoff play an important role in extending myointimal hyperplasia independent of method and severity of the arterial injury during angioplasty. PMID- 1860230 TI - Cardiac epinephrine synthesis. Regulation by a glucocorticoid. AB - BACKGROUND: The heart can synthesize epinephrine. Homogenates of rat heart, which contain the enzymes phenylethanolamine N-methyltransferase (PNMT) and nonspecific N-methyltransferase (NMT), methylate norepinephrine to form epinephrine. The cardiac atrium contains primarily PNMT and the cardiac ventricle contains both PNMT and NMT. METHODS AND RESULTS: Rats were given the glucocorticoid dexamethasone at doses ranging from 0.2 to 20 mg/kg. Twenty-four hours later, cardiac atria, ventricle, skeletal muscle, and adrenal had increases in PNMT activity to as much as 230% of baseline. NMT activity was unchanged. Longer-term treatment with 1 mg/kg dexamethasone daily for 12 days increased cardiac PNMT activity about fivefold and also increased atrial epinephrine levels. Dexamethasone did not alter ventricular epinephrine levels but increased levels of both PNMT and catechol-O-methyltransferase, the major catabolic enzyme for epinephrine. After dexamethasone treatment, greater volumes of anti-PNMT antiserum were needed to decrease PNMT enzymatic activity, indicating that dexamethasone treatment resulted in greater amounts of PNMT and did not just activate existing PNMT molecules. Denervation of the masseter muscle of rats by unilateral superior cervical ganglionectomy markedly diminished tissue norepinephrine and epinephrine levels but had no effect on masseter PNMT or NMT levels. We have previously shown that chemical sympathectomy with 6 hydroxydopamine increases cardiac PNMT levels. These findings suggest that PNMT is an extraneuronal enzyme in both cardiac and skeletal muscle. CONCLUSIONS: Glucocorticoids have several cardiovascular effects, including increased cardiac output and blood pressure. Enhanced cardiac epinephrine synthesis may mediate some of these glucocorticoid effects. PMID- 1860231 TI - Improved blood flow during prolonged cardiopulmonary resuscitation with 30% duty cycle in infant pigs. AB - BACKGROUND: Sustained compression is recommended to maximize myocardial and cerebral blood flow during cardiopulmonary resuscitation (CPR) in adults and children. We compared myocardial and cerebral perfusion during CPR in three groups of 2-week-old anesthetized swine using compression rates and duty cycles (duration of compression/total cycle time) of 100 per minute, 60%; 100 per minute, 30%; and 150 per minute, 30%. METHODS AND RESULTS: Ventricular fibrillation was induced and CPR was begun immediately with a sternal pneumatic compressor. Epinephrine was continuously infused during CPR. Microsphere determined blood flow and arterial and sagittal sinus blood gas measurements were made before cardiac arrest was induced and after 5, 10, 20, 35, and 50 minutes of CPR. At 5 minutes of CPR, ventricular and cerebral blood flows were greater than 25 ml.min-1 x 100 g-1 and were not significantly different between groups. When CPR was prolonged, however, myocardial and cerebral blood flows were significantly higher with the 30% duty cycle than with the 60% duty cycle. By 35 minutes, all myocardial regions had less than 5 ml.min-1 x 100 g-1 flow with the 60% duty cycle. In contrast, CPR with the 30% duty cycle at either compression rate provided more than 25 ml.min-1 x 100 g-1 to all ventricular regions for 50 minutes. By 20 minutes, most brain regions received 50% less flow with the 60% duty cycle compared with animals undergoing CPR with the 30% duty cycle (p less than 0.05). Cerebral oxygen uptake was better preserved with the 30% duty cycle. Chest deformation from loss of recoil was greater with the 60% duty cycle compared with the 30% duty cycle. CONCLUSIONS: We conclude that the shorter duty cycle provides markedly superior myocardial and cerebral perfusion during 50 minutes of CPR in this infant swine model. These data do not support recommendations for prolonged compression at rates of 100 per minute during CPR in infants and children. PMID- 1860232 TI - Nonischemic sudden tachyarrhythmic death in atherosclerotic heart disease. PMID- 1860233 TI - Mechanism of cardiac defibrillation. A different point of view. PMID- 1860234 TI - Antiphospholipid antibodies and the heart. Lessons and pitfalls for the cardiologist. PMID- 1860235 TI - James B. Herrick Lecture. Matrices of decision making in cardiology. PMID- 1860236 TI - Antiarrhythmics and VPD suppression. PMID- 1860237 TI - Dipyridamole thallium test. Is it useful for predicting coronary events after vascular surgery? PMID- 1860238 TI - Stroke prevention in atrial fibrillation trial. PMID- 1860239 TI - Thrombocytes and coronary heart disease. PMID- 1860240 TI - Has excimer coronary laser angioplasty finally found a niche? PMID- 1860241 TI - Interventional cardiology. The decade ahead. PMID- 1860242 TI - Chemical atherectomy. A novel approach to restenosis. PMID- 1860243 TI - Therapeutic fibrinolysis. What should follow? PMID- 1860244 TI - Adenosine. The signal of life? PMID- 1860245 TI - Discordance in results of right coronary intervention. PMID- 1860246 TI - Effects of medical and surgical therapy on postinfarction mortality rates. PMID- 1860247 TI - Environmental tobacco smoke and cardiovascular disease. PMID- 1860249 TI - Piebaldism: an autonomous autosomal dominant entity. AB - Piebaldism is a disorder in which the major clinical features are patchy hypopigmentation of the skin and a white forelock. The manifestations of piebaldism overlap with those of other genodermatoses, in particular the Waardenburg syndrome, and it is uncertain whether piebaldism is a distinct entity. We have documented a family in which seven affected members in three generations have gross piebaldism without any additional stigmata. The intrafamilial phenotypic consistency is suggestive that this autosomal dominant disorder has independent syndromic status. Linkage studies using conventional gene markers failed to identity the locus of the faulty gene. PMID- 1860248 TI - Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the Utstein Style. A statement for health professionals from a task force of the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, and the Australian Resuscitation Council. PMID- 1860250 TI - Automated multiple-cell karyotyping: a clinical feasibility study. AB - In order to increase the efficiency of the Magiscan metaphase location and karyotyping system, its software and mode of operation have been changed. In the new multiple-cell karyotyping method, interactions by the operator are only required for relocation and counting of metaphases, but not for karyotyping. Metaphases are located and their coordinates recorded automatically as before. The first metaphase in the list is relocated, displayed on the screen, and counted by the operator. It is then karyotyped automatically while the operator relocates and counts the next metaphase in the list. This procedure continues until an appropriate number of metaphases have been counted and karyotyped. Finally a composite karyotype is printed out. Each karyotype is represented by a column of 23 chromosome pairs (1-22 and XX or XY) and all columns are lined up next to each other. Most chromosomes are correctly classified into the composite karyotype. Minor structural abnormalities are detected by comparing pairs of homologues. Overlapped, close touching, and grossly abnormal chromosomes are often misclassified or rejected and shown beneath the classified chromosomes. A trained cytotechnician can easily detect even small chromosome abnormalities on the composite karyotype. A clinical feasibility study indicates that the procedure can be used for routine cytogenetic analysis. PMID- 1860251 TI - A 15-item checklist for screening mentally retarded males for the fragile X syndrome. AB - A 15-item checklist, including physical and behavioral features frequently observed in fragile X syndrome, was used in a prospective study of 188 mentally retarded males in order to identify males at risk for this syndrome. Of the 188 males, 19 were found to have the fragile X syndrome, while the remaining 169 males had no recognizable cause of their mental retardation, including normal chromosomes. Significant differences (p less than 0.01) were found between mentally retarded males with and without the fragile X syndrome with increased hyperactivity; shorter attention span; more tactile defensiveness, hand-flapping, perseverative speech, and hyperextensibility; large ears and testes; higher frequency of simian creases or Sydney lines and plantar creases; and more positive family histories of mental retardation in the fragile X syndrome males. Multiple regression and discriminant analyses of the 188 males indicated several physical features were useful predictors for inclusion in the fragile X syndrome group. An overall correct classification rate of 93% was achieved based on 6 variables (plantar crease, simian crease, hyperflexibility, large testes, large ears, and a positive family history of mental retardation) that were entered into the discriminant equation. Therefore, our experience with a 15-item checklist suggests the potential of screening for the fragile X syndrome in mentally retarded males and that 6 of the 15 variables were particularly good predictors of this syndrome. PMID- 1860252 TI - Metaphyseal acroscyphodysplasia. AB - Based on two independent personal cases and a pair of sibs from the literature, we delineate a new category of bone dysplasia with cup-shaped large metaphyses, for which the name metaphyseal acroscyphodysplasia is suggested. The main clinical features are severe growth retardation, micromelia predominating in the lower limbs, knee flexion, and severe brachydactyly. The radiological aspect of the knees is very specific: the lower femoral and upper tibial epiphyses embed themselves in their metaphyses, which are severely cup-shaped. Premature central epiphyso-metaphyseal fusion and gross deformation, or even coalescence, of the femoral condyles may occur. The femoral diaphyses are very short and broad, and there is progressive coxa valga. Bowed and/or short stubby tibiae with cone shaped metaphyses, and varus deformity of the tibio-astragalian joint are other features. Slight deformations of the long bones occur in the upper limb. Severe brachydactyly, brachymesophalangy, phalangeal and metacarpal cone-shaped epiphyses and irregular, bent and shortened diaphyses are the main signs of hand involvement. Psychomotor retardation is present in 3/4. Autosomal recessive inheritance is likely. PMID- 1860254 TI - Acrodysostosis in two generations: an autosomal dominant syndrome. AB - Acrodysostosis is a rare syndrome characterized by growth retardation, peripheral dysostosis and mental deficiency. X-rays reveal generalized shortening of metacarpals, metatarsals and phalanges, hyperplasia of the first ray of the feet and premature skeletal maturation. Occasionally abnormal interpedicular spinal spaces, increased mandibular angle and hearing loss have been observed. We report a 19-year-old woman and her daughter examined at birth and subsequently at 6 years of age. The clinical and radiological characteristics are those of acrodysostosis. The syndrome is easily recognized at birth. The generalized corporal shortening is progressive and could be due to premature closing of epiphyses. The finding of an affected mother and her daughter support the postulate that acrodysostosis is inherited as an autosomal dominant syndrome. PMID- 1860253 TI - Monozygotic twin girls with diploid/triploid chromosome mosaicism and cutaneous pigmentary dysplasia. AB - Diploid/triploid mosaicism is an uncommon clinical syndrome with a subtle but distinctive phenotype. Characteristic features include prenatal and postnatal asymmetric growth deficiency, triangular and/or asymmetric facies, micrognathia, finger and/or toe syndactyly, clinodactyly, single transverse palmar creases, male genital anomalies, hypotonia and psychomotor retardation. This disorder is underdiagnosed because in 70% of cases the triploid cell line is only seen in fibroblasts. In cases in which a triploid cell line is found in lymphocytes, it usually occurs in less than 5% of cells. While some reports of diploid/triploid mosaicism have mentioned unusual skin pigmentary patterns, including hypomelanosis of Ito, it was only recently recognized that this is a helpful diagnostic clue in mosaic chromosome disorders. We report monozygotic twin girls with diploid/triploid mosaicism whose cutaneous pigmentary dysplasia led to their diagnosis. PMID- 1860255 TI - Association of annular pancreas and duodenal obstruction--evidence for Mendelian inheritance? AB - This report presents a family with two individuals in two successive generations who were affected by annular pancreas and high duodenal obstruction. An argument for autosomal dominant transmission and implications for appropriate team management are discussed. PMID- 1860256 TI - Interstitial deletion of chromosome 2q associated with ovarian dysgenesis. AB - In the present report we describe a girl with mental retardation, Dandy-Walker malformation, craniofacial anomalies, cardiac defect, and ovarian dysgenesis associated with an interstitial deletion of chromosome 2. The interstitial deletion in the proband was associated with an apparently balanced translocation involving chromosomes 2 and 7 in the father. PMID- 1860257 TI - Hypothesis: association of the critical region of trisomy 18 and 18q2--syndrome with dermatoglyphic findings and a growth suppressor (deleted in colon cancer) locus. AB - Evidence from the literature is reviewed to suggest that when fingertip dermal ridge patterns in chromosomal deletion syndromes are characteristic of the opposite spectrum of the developmental scale from patterns found in cases trisomic for the same chromosomal region, the association may be a consequence of loci with growth regulatory functions. Evidence is presented that DNA markers at 18q21 should be the first candidate sequences to be used to test this hypothesis in families with fingertip arches segregating in an apparent autosomal dominant fashion. PMID- 1860258 TI - IBM-PC compatible software for establishing metacarpophalangeal pattern profiles. AB - We briefly present software for performing metacarpophalangeal pattern (MCPP) profile analysis, which runs on generally available low-cost IBM (PC, XT, AT) and compatible PCs. The program is easy for the medical geneticist to handle and apply. We compared the mean MCPP of our own patients with Ullrich-Turner syndrome with the mean MCPP for Ullrich-Turner patients originally published by Poznanski. PMID- 1860259 TI - [Innovations in Tubinger and IMZ-implant systems]. PMID- 1860260 TI - [Bonefit implant models with Swiss precision with minimum instruments and maximum success]. PMID- 1860261 TI - Conventional treatment of idiopathic nephrotic syndrome and membranous nephropathy in adults. AB - This article is a review of the results of corticosteroid and immunosuppressive treatment in adults with idiopathic nephrotic syndrome. Adults with minimal change nephropathy usually require a prolonged administration of corticosteroids to achieve remission which, in itself, carries the risk of severe and even life threatening complications. Therefore, intravenous high-dose steroid pulses, alternate-day prednisone, short courses with cytotoxic agents and long-term administration of azathioprine have been suggested as alternatives to the classical prolonged corticotherapy. While most patients with focal-segmental glomerulosclerosis do not respond to short-term prednisone, almost half of the patients with nephrotic syndrome will attain remission with a more prolonged administration of corticosteroids and/or cytotoxic agents. A six-month course of methylprednisolone and chlorambucil preserves renal function and reduces the proteinuria in many patients with membranous nephropathy, even in the presence of initial renal insufficiency. Thus, there is growing evidence that corticosteroids and/or immunosuppressive agents can favorably alter the natural course of disease in many patients with idiopathic glomerulonephritis. However, these agents have a low therapeutic index. Further studies are needed to find more effective and less toxic treatment approaches in patients with primary glomerulonephritis. PMID- 1860262 TI - Mechanism of action of cyclosporin A and rationale for use in nephrotic syndrome. AB - Cyclosporin A (CyA, Sandimmun) is the forerunner of a new generation of immunosuppressive drugs. It is highly effective in both antibody- and cell mediated immunity and in inhibiting chronic inflammatory reactions. Cyclosporin A is, therefore, widely used to prevent rejection in clinical organ transplantation and appears to be very promising in the treatment of several autoimmune diseases. Cyclosporin A is not only effective when given at the time of sensitization (prevention of disease), but also when administered therapeutically during an immune response, such as during the active course of an autoimmune disease. The most important aspect of its immunosuppressive mechanism is the inhibition of lymphokine production secreted by activated T cells. The pharmacological effects of CyA are rapid in onset, dose-dependent and often quickly reversible when treatment is stopped. PMID- 1860263 TI - Cyclosporin A (Sandimmun) in nephrotic syndrome. Proceedings of a workshop. November 5, 1990, Nice, France. PMID- 1860264 TI - Epidemiology and natural course of idiopathic nephrotic syndrome. AB - The term "idiopathic nephrotic syndrome" is poorly defined and is used to refer to a variety of glomerular lesions. This article seeks to clarify the situation by considering the case for treating minimal-change nephropathy, focal and segmental glomerulosclerotic lesions, and mesangioproliferative lesions with predominantly IgM deposition as separate disease entities. In children, nephrotic syndrome has a pattern different from that in adults, in whom a wider pathogenetic spectrum is seen. There is support for the use of prospective clinicopathological data as the basis of identifying those patients with nephrotic syndrome who will progress to end-stage renal failure. Very heavy, persisting proteinuria is one marker of such progression and is also an indicator of metabolic complications, such as cardiovascular disease, which further increase the risks of mortality and morbidity in this group of patients. PMID- 1860265 TI - Treatment of idiopathic nephrotic syndrome with cyclosporin A in children. AB - Cyclosporin A (CyA, Sandimmun) was given to 71 children with idiopathic nephrotic syndrome, 45 of whom were steroid-dependent with signs of steroid toxicity, and 23 who were steroid-resistant. Cyclosporin A was effective in 80% of the steroid dependent patients, allowing cessation of corticosteroid treatment. However, most of these patients relapsed when CyA was tapered or withdrawn. In these patients, CyA may be required for long periods of time. Conversely, CyA was less effective in steroid-resistant patients; only 7% achieved remission with CyA alone. Cyclosporin A in association with prednisone may be an effective alternative as 8 out of 14 patients entered remission with this treatment combination. Serial renal biopsies were performed in 43 patients to evaluate the potential nephrotoxicity of the treatment. Eighteen patients developed significant tubulointerstitial lesions which were attributable to CyA nephrotoxicity. The risk of developing chronic nephrotoxicity appears to be higher in steroid resistant patients, and was not related to the duration of treatment. Cyclosporin A nephrotoxicity can develop in patients with normal renal function. PMID- 1860266 TI - Treatment of adult idiopathic nephrotic syndrome with cyclosporin A: minimal change disease and focal-segmental glomerulosclerosis. Collaborative Group of the French Society of Nephrology. AB - Two open studies were conducted to determine the efficacy and tolerance of cyclosporin A (CyA, Sandimmun) 5 mg/kg/day. Sixty-four patients received CyA as monotherapy, and efficacy was assessed at three months; in 48 other patients, CyA was given with prednisone 12-15 mg/kg/day, and efficacy was assessed at six months. Of these 112 patients, 14 withdrew prematurely because of adverse events or other reasons, and a further nine patients were excluded for protocol violation. The remaining 98 patients were considered valid for the evaluation of efficacy (52 with minimal-change disease [MCD] and 46 with focal-segmental glomerulosclerosis [FSGS]; 37/98 were steroid-dependent [SD], and 61/98 were steroid-resistant [SR]). The remission:failure rate depended on histology (36:16 in MCD, 11:35 in FSGS) and steroid response (25:12 in SD, 22:39 in SR). The rate of remission was highest in SD MCD (71%) and lowest in SR FSGS (20%; chi square = 18.6, p less than 0.001). Tolerance was assessed by serum creatinine and, in 36 cases, by repeat renal biopsy at six to 42 months. Serum creatinine was remarkably stable in MCD. Rising creatinines were observed mostly in cases of SR FSGS, particularly those who had pretreatment interstitial lesions; this was considered due to both an increase of interstitial lesions and progression of the glomerular lesions of FSGS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860267 TI - Current status of cyclosporin A in the treatment of membranous, IgA and membranoproliferative glomerulonephritis. AB - The effects of cyclosporin A (CyA, Sandimmun) therapy in various types of primary glomerular diseases are discussed. In membranous nephropathy, the data strongly support a positive effect in this disorder, but there have been no control trials thus far to indicate the risk-benefit ratio, the need for adjunctive therapy such as steroids, or what to expect in terms of time to response or duration of response. The risk of nephrotoxicity needs to be more precisely quantitated both from a functional and pathological perspective. Proper prospective controlled trials are needed to establish the safety and efficacy of CyA in this disease. In both IgA and membranoproliferative glomerulonephritis, the data are more sparse. Although isolated studies have suggested a benefit in both these categories, the risks are also evident and more careful pilot studies are indicated before any further conclusions can be drawn as regards the use of this agent in these disorders. PMID- 1860268 TI - Safety and tolerability of cyclosporin A (Sandimmun) in idiopathic nephrotic syndrome. Collaborative Study Group of Sandimmun in Nephrotic Syndrome. AB - The safety and tolerability of cyclosporin A (CyA, Sandimmun) in idiopathic nephrotic syndrome were analyzed in 661 patients enrolled in 10 clinical studies. The majority had minimal-change nephropathy (MCN, 34%) or focal-segmental glomerulosclerosis (FSGS, 33%). The safety experience covered 435 patient years of CyA exposure. The initial CyA dose averaged 5 mg/kg/day in adults and 6 mg/kg/day in children, and was further titrated according to efficacy or adverse reactions. Relevant CyA-induced renal dysfunction occurred almost exclusively in patients (mostly FSGS) who had abnormal baseline renal function. Renal tolerability was better in patients who had complete remission of nephrotic syndrome than in those who did not respond to treatment. However, in the latter, the risk was still relatively low if CyA treatment was stopped after three to four months of treatment. Sixty-nine patients had a renal biopsy performed after one to three years of continuous CyA therapy, and CyA-associated nephropathy, especially interstitial fibrosis, was seen in a few of these patients. Kidney biopsies may therefore be advisable in MCN patients treated successfully for one to two years and in whom further CyA therapy is indicated. Hypertension occurred in approximately 10% and was usually well controlled with conventional antihypertensive therapy. There were a few infectious complications, but the course of these was not unusual. Malignancies developed in five patients, including Hodgkin's lymphoma in two. Overall, adverse reactions resulted in CyA treatment discontinuation in 7.4% of patients, half of them because of renal dysfunction. PMID- 1860269 TI - Conventional therapy for idiopathic nephrotic syndrome in children. AB - In children, the most frequent type of idiopathic nephrotic syndrome is the minimal-change nephrotic syndrome (MCNS). Its treatment is aimed at inducing remission, preventing relapses and avoiding side-effects. Minimal-change disease is responsive to immunosuppressive therapy. The conventional treatment consists of glucocorticosteroids and the most widely used derivative is prednisone. Initial treatment should be intensive, for example, prednisone for 12 weeks, in order to reduce the risk of subsequent relapse. Treatment of relapses should be standardized in order to categorize the patient's disease for further treatment. If a frequent relapser develops signs of steroid toxicity, alkylating drugs should be prescribed: cyclophosphamide or chlorambucil for eight weeks for frequent relapsers who are not steroid-dependent; cyclophosphamide for 12 weeks for those who are. In steroid-resistant cases, a renal biopsy is indicated and treatment should be administered according to histological changes. PMID- 1860270 TI - Role of macrophages in onion-bulb formation in localized hypertrophic mononeuritis (LHM). AB - A unique pathogenetic process for onion-bulb (Ob) formation is disclosed with disclosed with immunohistochemistry and electron microscopy. Biopsy of a swollen segment of tibial nerve from a 42 year-old white female histologically demonstrated diffuse and angiocentric lymphocytic infiltrate in both endo- and perineurium with occasional lymphofollicular formation. Extensive Ob formation of nerve fibers was most striking with or without associated lymphocytes. Axis cylinders were intact in the majority of Ob. Immunocytochemically, Ob are composed of alternately laminated leaflets of Schwann cells (S100+) and mononuclear macrophage (HAM56+/LeuMl+/Muramidase+) processes but no perineurial (EMA+) cells. Immunohistochemical evidence of antigen presentation (HLA DR/LN3+/Ia+) was confined to macrophages. Electron microscopy insinuates that intricate interactions between macrophages and Schwann cells exists. Putative inhibition of remyelination along with proliferation of Schwann cells most probably is secondary to the effects of macrophages secretory products. No direct participation of B or T lymphocytes was detected in Ob. Thus, modified macrophages may emit a factor for concomitantly promoting proliferation of Schwann cells and an enzyme for myelin breakdown. In addition, only a few macrophages could be detected in some Ob and could be easily overlooked or misinterpreted as "vacuolated fibroblasts", if no immunohistochemical correlation is made, as modified macrophages making the external leaflets of Ob are more vacuolated. PMID- 1860271 TI - Wernicke's encephalopathy in a child with acute lymphoblastic leukemia treated with polychemotherapy. AB - We report on a 3 3/4-year-old girl with acute lymphoblastic leukemia. Polychemotherapy caused a complete remission of the tumor. Six months after treatment was started, the patient developed vomiting and diarrhea necessitating parenteral nutrition. Disturbance of eye movements appeared 4 weeks later. The patient died suddenly 3 days after their manifestation. Autopsy revealed Wernicke's encephalopathy. This case demonstrates the need for thiamine substitution in infants with malignant diseases. PMID- 1860272 TI - Tubular adenoma of choroid plexus: a case report. AB - A case of choroid plexus neoplasm histologically composed of tubular structures lined by a layer of cuboidal epithelium is reported. The neoplasm was located in the fourth ventricle of a 26-year-old man. The intense positivity for antisera anti-vimentin, anti-cytokeratin, anti-EMA and anti-S100 protein exhibited by these cells was consistent with choroid plexus origin. The patient is alive and in good health 5 years after surgery. The lesion represents a benign choroid plexus neoplasm not previously reported. The name "tubular adenoma of choroid plexus" is suggested for this variant. PMID- 1860273 TI - Cholesterol screening management of Florida's pediatric population. AB - The current cholesterol screening and management of Florida's pediatric population is evaluated utilizing a questionnaire mailed to 1,534 pediatric health care providers. Twenty percent of the physicians responded. Of the respondents, 65% do not routinely screen for the presence of hypercholesterolemia. Only 28% of the respondents obtain serum total cholesterol measurements in accordance with the American Academy of Pediatrics Committee on Nutrition recommendations. The serum total cholesterol concentration prompting treatment was 240 mg/dL (6.2 mM). Dietary counseling alone, or in combination with exercise, was the initial treatment approach recommended by 98% of the responding physicians. Dietary education for the hypercholesterolemic patient was provided by both dieticians (46%) and physicians (42%). If the initial dietary intervention was unsuccessful, 48% of the physicians would begin medical therapy. The most commonly prescribed medication was a bile acid sequestrant (70%), with the majority (52%) referring their patient to a subspecialist for evaluation and care. PMID- 1860274 TI - Health and safety in day care: parental knowledge. AB - Because injuries and illnesses occur among children, even in licensed child care facilities, parents need to be aware of existing hazards. We developed a questionnaire to assess parental knowledge of 16 health and safety features in their child's care facility. These health and safety features were identified by parents, in a pilot study, as being the most important features in a child care facility. This questionnaire was completed by 91 parents who use day care. Parents were well-educated employees of a health care institution. Our results indicate that even well-educated parents often do not check child care facilities for health and safety features. Parents tolerated a mean of 9.3% of 16 unsafe features and did not know the status of 22.4% of the features. Fifteen percent of the children has been removed from their child care facility because of health and safety concerns, 7.7% reported an injury. Our results suggest that it is important that physicians, during well child visits, include discussions about health and safety issues in the day care environment. PMID- 1860275 TI - An investigation into the etiology of irritable hip. AB - A prospective review has been made of 111 children who presented with acute hip pain to determine it's etiology and assess the need for multiple investigations at presentation. There was no clinical hematological, serological or bacteriological evidence to identify positively patients with an irritable hip, neither was there good correlation with a history of infection. An effusion was diagnosed by ultrasound in 71% but there were no factors, either clinically or by investigation, to differentiate between patients with or without an effusion. We conclude that multiple investigations to find a source of infection in patients with irritable hip are not warranted as they are rarely positive, seldom affect management and are of no help in investigating the etiology of irritable hip. PMID- 1860276 TI - Our children's health: prospects for the 1990's. PMID- 1860277 TI - Chronic renal insufficiency in infants and children. PMID- 1860278 TI - Encephalopathy and brain stem dysfunction in an infant with non-accidental carbamazepine intoxication. PMID- 1860279 TI - Genitourinary gonorrhea presenting as mild arthritis. PMID- 1860280 TI - Hemorrhagic complications of kidney biopsy. PMID- 1860281 TI - Treatment of otitis media twice daily for five days. PMID- 1860283 TI - A clinical evaluation of the Sulcabrush. AB - The purpose of this study was to compare the effectiveness of a unituft brush in combination with a conventional brush for plaque removal and maintenance of gingival health. Thirty patients presenting for routine dental care were examined and scored for plaque deposits and gingival inflammation. All subjects received a dental prophylaxis consisting of removal of all supragingival and subgingival deposits and polishing of the clinical crowns. Subjects were subsequently evaluated at 1 week, 6 weeks and 12 weeks. The addition of a unituft brush to the patient's regimen of oral hygiene procedures resulted in significant reductions at 12 weeks in both plaque scores (p less than .05) and gingival inflammation (p less than .01) when compared to the use of the conventional brush alone. PMID- 1860282 TI - Staining and antimicrobial properties in vitro of some chlorhexidine formulations. AB - Dietary staining studies have proved useful determinants of chlorhixidine activity in mouthrinse products, and results correlate with plaque inhibitory effects. This investigation compared the staining and antimicrobial action in vitro of two known and similarly effective, commercially available chlorhexidine mouthrinses with a reformulated 0.1% chlordexidine preparation. After adjustment for original concentration the 0.2%, 0.12% and reformulated 0.1% products had essentially similar, minimum inhibitory-dilution values against standard test organisms. The 0.1% preparation was more effective against Capnocytophaga ochracea, suggesting additional antimicrobial activity derived from an ingredient other than chlorhexidine. The staining in vitro of tooth and acrylic specimens was equivalent with the 0.2% and 0.12% products. By comparison with equivalent concentrations of the diluted 0.2% preparation, the 0.1% formulation produced less staining, particularly when diluted. The data suggest that the 0.1% formulation, when used in diluted form as recommended by the manufacturer, may have slightly reduced plaque-inhibitory effects by comparison to the 0.2% or 0.12% products. However, the results raise the question whether chlorhexidine solutions could be formulated to reduce side effects, in particular, tooth staining at the expense of some loss of antiplaque activity. PMID- 1860284 TI - The effects of metronidazole administration on clinical and microbiologic parameters of periodontal disease. AB - The purpose of this study was to assay the concentration of metronidazole in gingival fluid, to correlate clinical and microbiologic parameters of periodontal disease to each other and to the gingival fluid concentration of the drug. Ten subjects with a minimum of two contralateral pairs of periodontal pockets of greater than or equal to 5 mm were utilized. One side of the mouth was selected to serve as the root-planed site while the other was left untreated. On day 0, plaque and bleeding-time indexes and probing depths were recorded. Subgingival plaque was analyzed using phase contrast microscopy. When root planing was completed, the subjects were prescribed either metronidazole or placebo three times daily for seven days. Within 24 hours of the last dose, and thereafter at intervals of 1, 2 and 3 weeks, fluid samples were assayed for metronidazole. Clinical and bacterial data were likewise recorded. The results indicate that root planing with metronidazole appears to be more effective in promoting periodontal health than root planing alone. Concentrations of metronidazole ranging from 5 to 20 micrograms/ml were detectable in fluid samples obtained within 24 hours of administration of the last dose. No discernible levels could be found in samples taken at the longer intervals. PMID- 1860285 TI - Taurolin as an oral rinse. I. Antimicrobial effects in vitro and in vivo. AB - Taurolin, a synthetic antimicrobial agent, has been suggested to be of potential value as an inhibitor of dental plaque. Although data on the antibacterial activity of Taurolin are available there is a dearth of information for effects on oral bacterial isolates and antibacterial activity in the mouth. This study assessed the in vivo and in vitro antibacterial properties of a Taurolin rinse by a) determining the MID values against seven oral isolates and b) measuring salivary bacterial counts following a single rinse. By comparing activity with chlorhexidine, it was hoped to determine substantivity and predict the relative ability of Taurolin to inhibit plaque through an antimicrobial effect. For Taurolin, MID values against the test organisms were found to range between 1:20 and 1:80, while for chlorhexidine, values between 1:320 to 1:640 were obtained. The effects on salivary bacterial counts revealed that Taurolin significantly reduced salivary bacterial counts compared to saline up to 5 hours post rinsing, but was significantly less effective than chlorhexidine after 30 minutes and up to 7 hours. Results indicate that Taurolin has some persistence of antimicrobial activity in the mouth. This suggests that Taurolin would possess some plaque inhibitory properties albeit less than chlorhexidine. These conclusions were confirmed in a subsequent investigation. PMID- 1860287 TI - Comparative evaluation of test parameters in plaque removal. A preliminary report. AB - A comparative study was conducted to determine the effect of several parameters on the removal of simulated plaque. Streptococcus mutans grown in a 2% sucrose medium was allowed to deposit on porous ceramic tiles in the course of the culture growth to form simulated plaque. The tiles with the culture deposit were dried and stained with Safranin O stain, then used in the plaque removal studies. The parameters evaluated in the course of the study were (a) flowing cold water vs flowing hot water and (b) brushing with toothpaste alone vs brushing with hot water as well as brushing alone. It was observed that flowing hot water was more effective than flowing cold water in the removal of the simulated plaque. Brushing with hot water was found to be a more efficient means of removing the plaque than brushing with toothpaste or brushing alone. The study suggests that it is more effective to use hot water for plaque removal in the course of performing daily oral hygiene. PMID- 1860286 TI - Taurolin as an oral rinse. II. Effects on in vitro and in vivo plaque regrowth. AB - A Taurolin solution has been shown previously to possess antibacterial activity, not only by a bactericidal effect but also by reducing bacterial surface adherence. Such mechanisms may contribute to reduction in dental plaque in the mouth, however this remains to be determined. The present study assessed whether a Taurolin rinse could firstly effect bacterial surface growth and, secondly, whether the same rinse could reduce plaque regrowth over a 4-day period. The findings showed that the Taurolin reduced in vitro bacterial surface growth and in vivo plaque regrowth compared to saline, but was not as effective as a chlorhexidine rinse. The findings suggest Taurolin would probably have a moderate effect on plaque and gingivitis in longer-term use. PMID- 1860288 TI - Sugar consumption in Israeli Defense Forces personnel. AB - The per capita sugar consumption of the Israeli Defense Forces personnel has been determined during the years 1973-1986. Although a total decrease is noted, specific cariogenic items and confections are increased. This might explain, partially, the high dental treatment needs of the Israeli military population. Recommendations concerning the army dietary policy and health education programs are suggested. PMID- 1860289 TI - Malarial chemoprophylaxis and the healing of periodontal lesions. AB - A randomized study was carried out using 92 patients (39 taking a malarial chemoprophylactic agent and 53 not taking a chemoprophylactic agent) to investigate the rate of healing of ulcerative periodontitis after treatment. The chemoprophylaxis group who had been on 300 mg chloroquine weekly for at least one year and the non-chemoprophylaxis group who had not been on the regimen for at least one year were involved in the study which examined the global efficacy and assessment for pain relief over a period of 12 weeks after treatment for ulcerative periodontitis. A detailed, symtomatic and clinical assessment was made at biweekly intervals. Relief from pain was higher for the non-chemoprophylaxis group (94.2% vs. 46.2%, p less than 0.05). The global efficacy was statistically significant for the non-chemoprophylaxis group (87% vs. 38.4%, p less than 0.05). The outcome of treatment was not influenced by factors such as duration of chemoprophylaxis, initial severity of pain and smoking habits of the patients. PMID- 1860291 TI - Comparison of an herbal toothpaste with a fluoride toothpaste on plaque and gingivitis. AB - An herbal/bicarbonate toothpaste has received some attention from the public and profession following a number of studies which have reported beneficial effects of the paste on both plaque and gingivitis. The present study, one of several ongoing clinical trials, evaluated the toothpaste in mouthrinse form using a 19 day, no oral hygiene, triple-crossover design in which it was compared with a commercial fluoride toothpaste rinse and the antiplaque mouthrinse chlorhexidine. Over the three periods of the study an increase in plaque and gingivitis was seen for all three products. However, while significant reductions in both parameters were seen with chlorhexidine compared to the toothpastes, there were no significant differences between the herbal and fluoride toothpaste. From these findings it can be concluded that in the long term, the herbal/bicarbonate toothpaste may not exert significant therapeutic effects on plaque and gingivitis beyond that of a conventional commercial paste. Nevertheless, where there is a demand for a natural product, the herbal/bicarbonate paste may be a worthwhile alternative. PMID- 1860290 TI - The effect of sustained-release varnish of chlorhexidine in dental plastic shells on salivary Streptococcus mutans. AB - The suppression of S. mutans is a predominate factor in preventing tooth decay. Sustained-release-delivery varnish of chlorhexidine was applied to dental plastic shells and administered to eight volunteers to be worn while sleeping. Salivary bacterial samples were taken on days 0, 7, 14, 21, 28, 35. A statistically significant reduction in S. mutans counts was recorded during the course of the study while a non-significant reduction in the total bacterial counts was found. Our results indicate that the application of chlorhexidine in the form of slow release varnish in plastic shells is an effective intraoral drug delivery system resulting in reduction of S. mutans. PMID- 1860292 TI - Enamel fusion using a carbon dioxide laser: a technique for sealing pits and fissures. AB - The well-established enhanced resistance of lased enamel to demineralization is the basis for clinical application of the carbon dioxide laser to caries prevention. This in vitro study examined the effect of focused infrared laser radiation on sound enamel and early pit and fissure caries. Low power levels (2-5 W) induced localized melting and resolidification of enamel with little surface destruction. For sound fissures, fusion of enamel from the lateral walls of the fissure eliminated the fissure space, providing a sealant effect; while in carious fissures, carious enamel was vaporized and adjacent sound enamel fused to partially eliminate the defect. The technique for enamel fusion using CO2 lasers has potential application for sealing pits and fissures and producing physicochemical alterations in enamel which may have preventive benefits. PMID- 1860293 TI - Topical varnish containing strontium in a sustained-release device as treatment for dentin hypersensitivity. AB - The purpose of this study was to assess the effect of topical application of a sustained-release device in form of a varnish containing strontium chloride on dentinal hypersensitivity. Sixty teeth were selected in ten patients. The teeth were divided in a) varnish application containing strontium chloride, b) varnish application with no active ingredient, c) untreated teeth. Varnish application was carried out by the patients once daily for 30 days. Results show a marked decrease in hypersensitivity to both mechanical (54%) and thermal stimuli (38%) as compared to the placebo and untreated group. PMID- 1860294 TI - A comparison of 0.12% and 0.1% chlorhexidine mouthrinses on the development of plaque and gingivitis. AB - A number of commercially prepared chlorhexidine mouthrinses which are now available are formulated at concentrations lower than the more usual 0.2%. This study compared 0.12% and 0.1% chlorhexidine mouthrinses for effects on plaque regrowth and gingivitis, using a two 19-day period single-operator blind crossover study design on 14 healthy human volunteers. The 0.12% rinse was a commercial product previously shown as effective as a 0.2% rinse. The 0.1% rinse was a reformulated version of a 0.1% preparation commercially available at the time of this study. Plaque reformation was recorded on days 12 and 19 by score and area. Gingivitis was recorded at day 1, 12 and 19 by measuring gingival crevicular fluid, gingival index and bleeding on probing. The mouthrinses were used twice a day and as recommended by the manufacturer. Mean scores for plaque and gingivitis were mostly lower with the 0.12% rinse but only reached significance for plaque score on days 12 and 19 and for plaque area on day 19. Reformulation of the 0.1% would appear to have markedly improved the antiplaque properties to levels similar to a known effective commercially available 0.12% rinse. PMID- 1860295 TI - Patients' perceptions related to the use of infection control procedures. AB - An assessment was made of the public's attitudes toward infection control techniques utilized in dentistry. Five hundred and nine adults in the State of Maryland responded to a detailed telephone survey in late 1989. Respondents reported that most of their dentists (87.0%) wore gloves and 69.8% of the respondents preferred gloves. Respondents who were most concerned about AIDS also preferred the dentist to wear gloves (92.6%). Respondents received information about AIDS from various sources, chief of which were newspapers or magazines (29.0%) and television (27.3%) but 80.9% would read pamphlets on AIDS if they were available in the dentist's office. Finally, few (13.1%) had ever discussed AIDS with their dentist but most (78.6%) would be comfortable doing so. This study demonstrated that the public accepts and welcomes the use of barrier protection by dentists. The public also is willing to discuss AIDS and infectious diseases with dentists and would read AIDS information supplied by dentists. Given the continued spread of the AIDS epidemic, it is increasingly important for dentists to educate the public about AIDS as well as about the continued safety of the dental office. The public is receptive to this education. PMID- 1860296 TI - Long-term dissolution of mercury from a non-mercury-releasing amalgam. AB - The hazards of mercury from dental amalgams have long been recognized. This study examined the mercury release from a "non-mercury-releasing" dental amalgam, Composil, over a 104-week period. Four cylindrical specimens were incubated in 10 ml of purified water at 37 degrees C. The incubate was changed at the end of each 24-hour period and assayed for its mercury content at biweekly intervals. Mercury estimation was carried out using cold-vapor, atomic absorption spectrophotometry over a 104-week period. Results showed that the overall mean release of mercury was 43.5 +/- 3.2 micrograms/cm2/24 hr, and the amount of mercury released remained fairly constant during the duration of the experiment. This study showed that Composil releases mercury in quantities that far exceed those detected in other amalgam systems. PMID- 1860297 TI - Practical strategies for a plaque-control program. AB - With many patients the control of dental plaque is accepted as an important factor in the prevention and treatment of periodontal diseases. However, for others, because this aspect of oral hygiene is not yet totally understood or accepted, plaque control programs often prove to be frustrating and too time consuming for the general practitioner. This article provides some practical strategies to overcome common pitfalls in delivering a plaque-control program. PMID- 1860298 TI - Conference attendees told ISIS-3 shows equal efficacy, safety differences among thrombolytics. PMID- 1860299 TI - Labetalol for treatment of hypertension in a child. PMID- 1860300 TI - Antimicrobial dosages in guidelines for prevention of bacterial endocarditis. PMID- 1860301 TI - Therapy of acute thromboembolism with heparin and warfarin. AB - The indications, efficacy, dosage, administration, and monitoring of heparin and warfarin therapy for acute thromboembolic events are reviewed, with emphasis on recent changes in treatment recommendations. High-dose heparin therapy is indicated for acute deep-vein thrombosis and pulmonary embolism. Heparin therapy as an adjunct to thrombolytic agents for acute myocardial infarction is becoming increasingly accepted. Heparin therapy for acute thromboembolic events consists of a dosage that elevates the activated partial thromboplastin time to 1.5 to 2.0 times the control value; formerly, 1.5 to 2.5 times control was considered therapeutic. The recommended heparin dosage is a bolus dose of 70-100 units/kg followed by an infusion of 15-25 units/kg/hr. To prevent recurrent thromboembolism, most patients require long-term therapy following acute treatment; this typically consists of warfarin, which should be initiated on day 1 or 2 of heparin therapy whenever possible. For most indications, the intensity of warfarin has been reduced to a dosage that elevates the prothrombin time to 1.3 to 1.5 times control. Alternative therapies (low-molecular-weight heparins) and routes (subcutaneous heparin) should be further investigated. Current recommendations for heparin and warfarin therapy of acute thromboembolism include reduced intensity of both drugs and shortened duration of therapy. Since the therapeutic ranges for both heparin and warfarin therapy have been compressed, closer monitoring may be necessary to achieve and maintain adequate anticoagulation. PMID- 1860302 TI - Effect of ranitidine on the disposition of orally and intravenously administered triazolam. AB - The effect of orally administered ranitidine on the pharmacokinetic properties of orally and intravenously administered triazolam was determined. Twelve healthy males with a mean age of 35 years were enrolled in this four-way, randomized, crossover study. Each subject received a total of four treatments, each separated by one week. The treatments consisted of (1) one orally administered 0.25-mg triazolam tablet after treatment with ranitidine; (2) one orally administered 0.25-mg triazolam tablet, with no ranitidine pretreatment; (3) a 0.25-mg intravenous dose of triazolam after treatment with ranitidine; and (4) a 0.25-mg intravenous dose of triazolam, with no ranitidine pretreatment. Ranitidine pretreatment consisted of five 150-mg oral doses (as the hydrochloride salt) given every 12 hours; the last dose was given two hours before triazolam was administered. Blood samples were taken at intervals up to 12 hours after triazolam treatment. Serum triazolam concentrations were measured by modified high-performance liquid chromatography, and pharmacokinetic values were calculated. Pretreatment with ranitidine had no effect on the disposition of intravenously administered triazolam but significantly increased the area under the serum drug concentration-time curve of oral triazolam. Ranitidine pretreatment had no effect on triazolam's terminal elimination rate constant or on the time to reach maximum serum triazolam concentration. Ranitidine pretreatment increased the systemic availability of triazolam by increasing its absorption. PMID- 1860303 TI - Susceptibility of Xanthomonas maltophilia and amikacin-resistant gram-negative bacteria to newer antimicrobials. AB - The susceptibility of Xanthomonas maltophilia and amikacin-resistant gram negative bacteria to a variety of newer antimicrobials was determined. Sixty three amikacin-resistant isolates were collected from 61 inpatients at a tertiary care hospital between 1985 and 1988. The organisms included Xanthomonas maltophilia (24 isolates), Pseudomonas aeruginosa (16), Pseudomonas species (3), Serratia marcescens (10), Flavobacterium meningosepticum (4), Enterobacter species (3), Acinetobacter calcoaceticus var. anitratus (2), and Alcaligenes xylosoxidans (1). Amikacin resistance was initially determined by using the Kirby Bauer disk diffusion method. The isolates were batched, and the minimum inhibitory concentrations (MICs) of 11 antimicrobials including amikacin were measured by using the standard agar dilution method. Of the 63 isolates initially found to be amikacin resistant by the disk diffusion method, 37% were found to be amikacin susceptible by MIC testing. Of 38 truly amikacin-resistant isolates, 76% were susceptible to ciprofloxacin, 63% to ofloxacin, 50% to imipenem-cilastatin, 47% to cefoperazone, 45% to ceftazidime, 13% to ceftizoxime, 11% to aztreonam, 11% to ceftriaxone, 5% to cefotetan, and 3% to amdinocillin. Ciprofloxacin and ofloxacin inhibited X. maltophilia to the greatest degree, with median MICs of 1 microgram/ml each. Fifteen amikacin-resistant Ps. aeruginosa isolates were inhibited by ciprofloxacin, imipenem, and ceftazidime, with median MICs of 0.375, 3, and 2 microgram/ml, respectively. Of the antimicrobials tested, ciprofloxacin had the greatest activity against amikacin-resistant organisms in vitro. PMID- 1860304 TI - Appetitive conditioning in Octopus cyanea. AB - The performance of Octopus cyanea was studied in 3 appetitive conditioning situations. In Experiment 1, 2 groups were trained in a runway; a large reward produced faster acquisition when reinforcement was consistent and better subsequent performance on a partial schedule than did a small reward. In Experiment 2, activity in the vicinity of a feeder was measured, and in Experiment 3, latency and probability of response were measured in an automated version of a traditional conditioned attack situation (Boycott & Young, 1950). There was evidence of acquisition with continuous reinforcement in both experiments but in neither with partial reinforcement. All of the results can be understood in terms of growth and decline in the strength of stimulus-reinforcer associations with reinforcement and nonreinforcement. PMID- 1860305 TI - Behavior of Maudsley reactive and nonreactive rats (Rattus norvegicus) in three consummatory contrast paradigms. AB - Maudsley reactive (MR/Har) and nonreactive (MNRA/Har) rats (Rattus norvegicus) were tested in successive, simultaneous, and anticipatory contrast procedures. The MR/Har rats showed smaller successive negative contrast effects than the MNRA/Har rats when shifted from 32% to 4% sucrose, and the degree of contrast was smaller in animals of both strains than that typically obtained with unselected Sprague-Dawley derived rats. Chlordiazepoxide (4 and 8 mg/kg), which typically reduces contrast, did not influence degree of contrast in rats of either strain. Animals of both strains showed positive and negative contrast in the simultaneous contrast procedure, but degree of contrast in both cases was smaller in rats of the MR/Har strain. Animals of both strains also showed anticipatory contrast when a 0.15% saccharin solution preceded 32% sucrose in once-per-day pairings. In terms of latency to initiate licking, the MNRA/Har rats showed a contrast effect, but the MR/Har rats showed a "reinforcement" effect--shorter latency when saccharin preceded sucrose than when saccharin preceded saccharin. Open-field tests showed typical strain differences: The MNRA/Har rats ambulated more, reared more, defecated less, and showed less thigmotaxis than the MR/Har rats. PMID- 1860306 TI - Sound localization in small birds: absolute localization in azimuth. AB - Nine small birds of 3 species (Melopsittacus undulatus, Serinus canarius, and Poephila guttata) were trained in an operant procedure to fly to sound sources for food reward. The angle between the 2 sound sources was varied on a session-by session basis, and threshold (i.e., minimum resolvable angle) was taken as the angle that corresponded to a performance level of 75% correct. In all, thresholds were calculated for pure tones of 5 different frequencies, noise bands of 3 different spectral compositions, and species-specific contact or distance calls recorded from each of the 3 species. Thresholds for both simple and complex stimuli were larger than 25 degrees. There were statistically significant species differences for each stimulus set, but these differences were not correlated with species differences in head size. Birds with 1 ear plugged performed as well as binaural birds in this task. Birds deafened in 1 ear, however, performed at chance. PMID- 1860307 TI - Effect of intrauterine position and social density on age of first reproduction in wild-type female house mice (Mus musculus). AB - In laboratory strains of mice, reproductive maturation is influenced by both the fetal and the peripubertal social environments experienced by females. Intrauterine position (IUP) for female fetuses is identified by the number of adjacent males; where 0M have zero, 1M have one, and 2M have two male neighbors. We sought to confirm, using wild-type female house mice (Mus musculus), the previous finding in the CF-1 strain of laboratory mouse that males prefer 0M over 2M females as mates. We recorded the age at first reproduction for females of known IUP housed either individually with a male or in a group of 6 females and a male. In neither housing condition were there significant differences in age of first reproduction among females of different IUPs, but 0M females that were group housed had perforate vaginas at an earlier age than other group-housed females. Mean (+/- SE) age at first reproduction was 58.1 (+/- 3.3) for paired and 126.6 (+/- 5.1) for group-housed females. The reproductive suppression observed in the grouped females was probably due to the interaction of inhibitory urinary chemosignals, low body weights, and female dominance hierarchies. PMID- 1860308 TI - Snake aggregation pheromones: source and chemosensory mediation in western ribbon snakes (Thamnophis proximus). AB - Aggregation with conspecifics is a robust phenomenon among snakes that is mediated by chemical cues, although the source of such cues is unknown. Adult western ribbon snakes (Thamnophis proximus) discriminated between skin lipid extracts from conspecifics and those from a sympatric heterospecific snake, the corn snake (Elaphe guttata). Additionally, ribbon snakes were attracted to conspecific skin lipid-marked shelters when paired with control-marked shelters, but no preference was exhibited when shelters marked with E. guttata skin lipids were paired with control-marked shelters. Furthermore, prevention of chemical access to the vomeronasal organs of T. proximus eliminated the ability to respond to conspecific skin lipids. These results indicate that epidermal lipids are the source of chemical cues mediating attraction to shelters marked by conspecifics and that such signals are detected by the vomeronasal system. PMID- 1860309 TI - Impaired performance from brief social isolation of rhesus monkeys (Macaca mulatta): a multiple video-task assessment. AB - Social isolation has been demonstrated to produce profound and lasting psychological effects in young primates. In the present investigation, two adult rhesus monkeys (Macaca mulatta) were isolated from one another for up to 6 days and tested on 7 video tasks designed to assess psychomotor and cognitive functioning. Both the number and the quality (i.e., speed and accuracy) of responses were significantly compromised in the social isolation condition relative to levels in which the animals were tested together. It is argued that adult rhesus are susceptible to performance disruption by even relatively brief social isolation, and that these effects can best be assessed by a battery of complex and sensitive measures. PMID- 1860310 TI - Discriminating the sex of conspecifics by male Japanese quail (Coturnix coturnix japonica). AB - How male Japanese quail (Coturnix coturnix japonica) discriminate the sex of conspecifics at a distance was investigated by testing subjects with male and female stimulus birds on the other side of a small window after opportunities to copulate with females and again after repeated exposures to males in the absence of copulatory opportunity. Time spent near the window, frequency of window approaches, duration of window visits, rate of walking near the window, line crossings outside the window area, pecking the window, and crowing were measured. Subjects responded similarly in the presence of male and female stimulus birds during the first test block but discriminated the sex of conspecifics after noncopulatory exposures to males. The discrimination was evident in less locomotion and less crowing in the presence of females as compared with males and, as predicted by a discrimination learning hypothesis, developed largely through a change in responding to males. PMID- 1860311 TI - Learning by honeybees (Apis mellifera) on arrival at and departure from a feeding place. AB - The question of when in the course of a visit to a feeding place foraging honeybees (Apis mellifera) learn about its location was studied in Experiment 1 by moving the animals a short distance after they arrived and began to feed. A preference for the arrival place developed, although less rapidly than in control animals for which the arrival and departure places were the same. In Experiments 2-5, a distinctive object was used to define the location of the feeding place. When the object was removed after arrival or introduced only after arrival, the animals learned less about its color and shape than did control animals for which it was present throughout each visit. The results contradict the claim that honeybees learn about certain characteristics of a feeding place only on arrival and about others only on departure. PMID- 1860312 TI - Acute perforated diverticulitis: primary resection and anastomosis? AB - Surgical management of patients with acute colonic diverticulitis is evolving from multiple towards single operations. The patterns of presentation and treatment of 146 patients with acute perforated diverticulitis have been reviewed (1983-1988) using the Hinchey classification system (Stages I-IV). This paper focuses on the six patients who presented with fecal peritonitis (Stage IV disease), half of whom were treated by primary resection and anastomosis and the remainder by a Hartmann procedure. The mean length of stay was 18.7 +/- 7.9 days and 12.7 +/- 4.8 days with a mortality of zero and one, respectively. These data suggest that in selected patients who present with perforated diverticular disease, primary resection with anastomosis offers a possible alternative to other operative management. The presence of fecal peritonitis should no longer be considered an absolute contraindication to immediate bowel reconstruction. Furthermore, we suggest that this decision be based on the relative absence of concomitant disease, a satisfactory response to preoperative resuscitation, the availability of a surgeon experienced in colonic surgery, and attention to postoperative management. PMID- 1860313 TI - Choledochal cyst diagnosed in pregnancy. AB - A primigravid patient with a type 1 choledochal cyst is reported. Conservative management allowed completion of the pregnancy and vaginal delivery of a term infant. Postpartum, the choledochal cyst was excised and biliary tree drained. A review of the literature and discussion of management alternatives of choledochal cysts discovered during pregnancy is presented. PMID- 1860315 TI - The health care of AIDS patients. Requirements for administrative and organizational support within institutions. The Connecticut Infectious Disease Society. PMID- 1860314 TI - Ketorolac tromethamine. PMID- 1860316 TI - Message from your Medicare carrier. PMID- 1860317 TI - The implications of Wilder vs Virginia Hospital Association for state Medicaid programs. PMID- 1860318 TI - Colo-rectal. PMID- 1860319 TI - Osler and Marius the Epicurean. PMID- 1860320 TI - William J. Curran and American health law. PMID- 1860321 TI - Pentoxifylline and the microcirculation in hemorrhagic shock. PMID- 1860322 TI - Characteristics of pediatric intermediate care units in pediatric training programs. AB - BACKGROUND/OBJECTIVE: To assess effective alternate care sites for the technology dependent, but less acute critically ill child, we surveyed pediatric training programs to determine the availability and characteristics of non-neonatal pediatric intermediate care units. METHODS: A questionnaire was mailed to the program directors of all 226 United States pediatric residency programs in October 1988. Institutions were queried about pediatric residency program and hospital demographics, along with specific day-to-day management issues in an intermediate care unit. RESULTS: The intermediate care unit offers highly skilled nursing care with greater than 90% of the units primarily covered by RNs in a 1:2 or 1:3 RN/patient ratio. The technologies used in these units were similar to those technologies used in an ICU, and the average daily bed charge was 40% less than the average daily bed charge in an ICU. However, an intermediate care unit was present in only 33% of pediatric training programs and pediatric residents were not specifically trained to care for patients in these units; 37% of these units did not have daily attending physician/nurse/resident rounds, despite the complexity and degree of illness in the patients located in these units. In addition, greater than 20% of intermediate care units were predominantly staffed by RNs with degrees less than BSN. Thirteen percent of these units had a predominance of RNs with only routine experience. CONCLUSIONS: Standard levels of care and academic and financial guidelines should be established to optimize the value of pediatric intermediate care units. PMID- 1860323 TI - Pharmacokinetics of dopamine in infants and children. AB - OBJECTIVE: We studied the pharmacokinetics of dopamine in hemodynamically stable children. DESIGN: Prospective clinical trial. SETTING: Pediatric ICU. PATIENTS: Children (age 3 months to 13 yrs) recovering from cardiac surgery or shock. INTERVENTION: Plasma dopamine concentrations were measured at the steady state or at termination of infusion using high-performance liquid chromatography. RESULTS: The half-lives of distribution and elimination were 1.8 +/- 1.1 and 26 +/- 14 (SD) mins, respectively. The apparent volume of distribution was 2952 +/- 2332 mL/kg. The clearance rate was 454 +/- 900 mL/kg.min. Dopamine clearance was linearly related to dose only in patients who were also receiving dobutamine (r2 = .76, p less than .05). Hepatic and renal dysfunction did not affect the pharmacokinetics of dopamine. CONCLUSIONS: A relationship between dopamine and dobutamine that affects the disposition of these two drugs may exist. The pharmacokinetics of dopamine are variable even in hemodynamically stable children. Hepatic or renal function does not adversely affect the pharmacokinetics of dopamine. PMID- 1860325 TI - Comparative clinical trial of standard operative tracheostomy with percutaneous tracheostomy. AB - OBJECTIVE: To compare percutaneous tracheostomy with conventional operative tracheostomy. DESIGN: Randomized clinical trial. SETTING: The medical and surgical critical care units of a large, tertiary-care, private hospital. PATIENTS: Twenty-five male and 21 female translaryngeally intubated patients with respiratory failure, in whom tracheostomy was indicated on clinical grounds, were randomly assigned to one of two groups. INTERVENTIONS: The 24 patients in group 1 underwent conventional operative tracheostomy, and the 22 patients in group 2 underwent percutaneous tracheostomy. One patient in group 2 required tracheostomy on three separate occasions during a prolonged hospital stay. MEASUREMENTS AND MAIN RESULTS: Patients were examined daily throughout their hospital stays for adverse events related to the tracheostomy. In all patients who survived until decannulation, plain tomography of the trachea was performed within 3 days of decannulation. Repeat physical and tomographic examinations were performed 6 and 12 wks later. Fifty-eight percent (14/24) of the operative tracheostomies were associated with at least one complication, compared with 25% (6/24) of the percutaneous tracheostomies (p less than .05, 95% confidence interval 7% to 59%). Predecannulation problems were more frequent in group 1 patients than in group 2 (46% vs. 13%, respectively; p less than .01, 95% confidence interval 9% to 57%), as were later sequelae (88% vs. 27%; p less than .05, confidence interval 26% to 96%) in survivors. Group 1 patients were more likely to have multiple complications, and their complications tended to be more serious. CONCLUSION: In this study, percutaneous tracheostomy appeared to be superior to the conventional operation. PMID- 1860324 TI - Aortic-carotid artery pressure differences and cephalic perfusion pressure during cardiopulmonary resuscitation in humans. AB - OBJECTIVE: Animal studies have shown an aortic-carotid artery pressure difference during cardiopulmonary resuscitation (CPR), which compromises cerebral perfusion. This pressure difference is most marked with prolonged CPR and can be abolished with administration of high doses of epinephrine. To better understand the mechanism of cerebral blood flow during CPR in humans, we determined the aortic carotid artery pressure difference, the cephalic perfusion pressure (the carotid artery-jugular vein pressure difference), and thoracic inlet venous "valving" (the central venous-jugular vein pressure difference), while administering standard doses of epinephrine. DESIGN: Prospective study with randomization as to which side the carotid artery was catheterized. SETTING: The resuscitation room of a large urban hospital's emergency department. PATIENTS: Fifteen adults in normothermic, nontraumatic prehospital cardiac arrest treated according to Advanced Cardiac Life Support guidelines, including administration of 1 mg epinephrine iv every 5 mins. INTERVENTIONS: The descending aorta, cervical common carotid artery, internal jugular vein, and central venous system were catheterized. Pressures were recorded during standard CPR for 5 mins after administration of 1 mg epinephrine iv. MEASUREMENTS AND MAIN RESULTS: Most patients received CPR for greater than 20 mins before the first epinephrine dose and for greater than 45 mins before pressure recording as described above. There was no significant difference between aortic and carotid artery compression and relaxation phase pressures. The mean +/- SD compression central venous-jugular vein pressure difference was 22.1 +/- 15.0 mm Hg, and the mean cephalic perfusion pressure was 20.8 +/- 19.5 mm Hg. CONCLUSIONS: There is no clinically important aortic-carotid artery pressure difference during human CPR using the standard dose of epinephrine, even with prolonged CPR. Despite carotid artery patency and thoracic inlet venous valving, the cephalic perfusion pressure is low during CPR in humans. PMID- 1860326 TI - Accuracy of a mixed venous saturation catheter during acutely induced changes in hematocrit in humans. AB - OBJECTIVE: To determine the accuracy of in vivo mixed venous hemoglobin saturation (Svo2) measurements with a fiber optic thermodilution catheter during acute changes in hematocrit. DESIGN: Comparison of fiberoptic in vivo Svo2 values with in vitro Svo2 values obtained with a multiwavelength spectrophotometer. SETTING: Operating room in a university hospital. PATIENTS: Six consecutive patients who are Jehovah's Witnesses. MEASUREMENTS AND MAIN RESULTS: Before and after each step of hypervolemic hemodilution and after every 500 mL of blood loss, blood gases were analyzed and hemodynamic, hemoglobin, hematocrit, and in vitro and in vivo Svo2 measurements were made. Hematocrit values were measured in the range of 40% to 18%. Plotting all in vivo Svo2 values (n = 74) against the in vitro Svo2 measurements obtained during the entire study period gives r2 = .86. The accuracy of in vivo Svo2 measurements was not affected by changes in hematocrit or cardiac output. The Svo2 catheter value at the beginning of the study differed from the in vitro Svo2 value by -0.86 +/- 2.56% and at the end of the study period of 8 to 10 hrs by 0.71 +/- 3.04%. CONCLUSIONS: The accuracy of the studied fiberoptic continuous measuring Svo2 system was not affected by changes in hematocrit or cardiac output. No significant drift in the in vitro Svo2 measurements was observed. PMID- 1860327 TI - Thermogenic and metabolic effects of dopamine in healthy men. AB - OBJECTIVE: To assess the thermogenic response of dopamine at three different infusion rates and to analyze its effects on various biochemical variables. DESIGN: Randomized sequential experimental treatment bracketed by control periods. PATIENTS: Eight young healthy male volunteers with normal body weight (51 to 89 kg). INTERVENTIONS: Three experimental periods during which dopamine was administered iv in a randomized order at rates of 2.5, 5, or 10 micrograms/kg.min with one preinfusion baseline and two recovery periods in between. MEASUREMENTS AND MAIN RESULTS: A significant (p less than .01) increase in resting energy expenditure was observed in response to the two highest dopamine infusion rates (5 and 10 micrograms/kg.min), corresponding to 6% and 15% median increases, respectively, as compared with preinfusion values. At the lowest dopamine infusion rate, no variation in resting energy expenditure was observed. Dopamine induced a significant (p less than .01) increase in hyperglycemia at all three infusion rates, and, at the highest infusion rate, dopamine induced a significant (p less than .05) increase of plasma free fatty acid concentrations. Insulin plasma concentrations were significantly (p less than .05 to p less than 0.1) increased at the three dopamine infusion rates. CONCLUSIONS: Dopamine infusion produces a dose-dependent thermogenic effect and induces various metabolic actions in man. PMID- 1860328 TI - Gastric mucosal pH as a prognostic index of mortality in critically ill patients. AB - OBJECTIVE: To determine if measurements of gastric intramucosal pH have prognostic implications regarding ICU mortality. DESIGN: Prospective comparison of outcome. SETTING: General adult ICUs in two teaching hospitals. PATIENTS: Eighty consecutive patients age 18 to 84 yrs (mean 63.4), 50 men and 30 women, 55% in the medical and 45% in the surgical services. METHODS: Gastric intramucosal pH was measured on ICU admission and again 12 hrs later. A value of greater than or equal to 7.35 was used to differentiate between normal and low gastric intramucosal pH. MEASUREMENTS AND MAIN RESULTS: Fifty-four patients had a normal gastric intramucosal pH and 26 patients had a low gastric intramucosal pH on ICU admission. The mortality rate was greater in the low gastric intramucosal pH group (65.4% vs. 43.6%; p less than .04). The frequency of sepsis and the presence of multisystem organ failure also were greater in the low gastric intramucosal pH group (p less than .01). Further stratification of patients according to gastric intramucosal pH measured 12 hrs after admission showed a greater mortality rate in patients with persistently low gastric intramucosal pH when compared with patients with normal gastric intramucosal pH during the first 12 hrs (86.7% vs. 26.8%; p less than .001). CONCLUSIONS: Measurements of gastric intramucosal pH on ICU admission, and again 12 hrs later, have a high specificity for predicting patient survival in this ICU patient population (77.8% to 80.6%). Furthermore, given its relative noninvasive nature, tonometrically measured gastric intramucosal pH may be a useful addition to patient monitoring in the ICU. PMID- 1860329 TI - Serum aminoglycoside clearance is predicted as poorly by renal aminoglycoside clearance as by creatinine clearance in critically ill patients. AB - OBJECTIVE: To determine the relationships among serum aminoglycoside clearance, renal aminoglycoside clearance, measured creatinine clearance, and estimated creatinine clearance derived from a standard formula in critically ill patients. SETTING: A ten-bed general ICU in a university hospital. PATIENTS: Eighteen critically ill patients who were being treated with gentamicin or tobramycin for severe infections, and were hemodynamically stable. INTERVENTIONS: The various clearances were measured simultaneously after the administration of a dose of aminoglycoside by assaying serial blood samples for aminoglycoside and creatinine concentration, and by measuring the content of these substances in urine collected over the same time period. OUTCOME MEASURES: The slopes, intercepts and coefficients of determination (r2) of the various regressions were determined, along with the 95% confidence intervals for the prediction of serum aminoglycoside clearance from each other variable. RESULTS: Renal aminoglycoside clearance, creatinine clearance, and estimated creatinine clearance accounted for only 58%, 59%, and 62%, respectively, of the variance in serum aminoglycoside clearance. Only 64% of the variance in renal aminoglycoside clearance was explained by creatinine clearance. Substantial and variable nonrenal aminoglycoside clearance was evident. CONCLUSIONS: The 95% confidence intervals for the prediction of serum aminoglycoside clearance from each index of renal function indicated that none of these indices provided acceptable accuracy for the prediction of serum aminoglycoside clearance and dosage requirements in critically ill patients. Renal aminoglycoside clearance was not better than creatinine clearance in this respect, and thus no other index of renal function is likely to be more accurate. This finding implies that the only accurate method of determining the dose requirements to achieve target serum concentrations in such patients will be individualized pharmacokinetic dosing. PMID- 1860331 TI - Cardiothoracic variables measured by bioelectrical impedance in preterm and term neonates. AB - OBJECTIVE: To report the range of normal values for impedance-derived cardiac output, stroke volume, and the baseline transthoracic impedance in the healthy preterm and term neonate over the weight range generally found in the intensive care nursery. DESIGN: Prospective, case-referent study. SETTING: University medical center special care and term nurseries. PATIENTS: Twenty-seven preterm and 25 term newborns with no evidence of cardiovascular problems. INTERVENTIONS: We determined the values for impedance cardiac output and stroke volume to be used as reference values. Also measured was the baseline transthoracic impedance, a number that reflects the air/fluid ratio of the thorax. MEASUREMENTS AND MAIN RESULTS: Stroke volume and stroke volume index were, respectively, 2.0 +/- 0.8 (SD) mL and 1.4 +/- 0.5 mL/kg for preterm infants, and 5.0 +/- 2.0 mL and 1.6 +/- 0.7 mL/kg for term neonates. Cardiac output and cardiac index were, respectively, 304 +/- 114 mL/min and 214 +/- 68 mL/min.kg for preterm newborns, and 648 +/- 244 mL/min and 205 +/- 78 mL/min.kg in term newborns. These values compared favorably with published values utilizing other techniques for these populations. Both cardiac output and stroke volume were linearly correlated to body weight, being largest in the heavier neonates. Transthoracic impedance values were 42.7 +/- 9.0 ohms and 6.7 +/- 1.7 ohms/cm for preterm infants and 32.3 +/- 4.3 ohms and 3.9 +/ 0.6 ohms/cm for term infants. Transthoracic impedance and transthoracic impedance/cm values were correlated negatively to body weight and were curvilinearly related to body weight. CONCLUSIONS: These values for transthoracic impedance and transthoracic impedance/cm are the first reported using the standard electrode lead configuration in neonates. PMID- 1860330 TI - Acute Physiology and Chronic Health Evaluation (APACHE II) score and outcome in the surgical intensive care unit: an analysis of multiple intervention and outcome variables in 1,238 patients. AB - OBJECTIVE: To assess the statistical association of the Acute Physiology and Chronic Health Evaluation (APACHE II) score with multiple intervention and outcome variables in surgical ICU patients. DESIGN: Continuous data collection on every patient admitted to the surgical ICU for a 21-month period. MATERIALS AND METHODS: For every admitted patient in the surgical ICU, APACHE II scores were calculated and the relationship between APACHE II score as an independent predictor of outcome was assessed with multiple outcome variables selected for study. The outcome and intervention variables tested included: treatment intervention measures such as days on ventilator; days with an arterial catheter, central venous catheter, triple lumen catheter, pulmonary artery catheter; days receiving total parenteral nutrition; days receiving tube feedings; number of transducers per days in the ICU; number of infusion pumps per ICU days, days in the hospital, number of complete blood counts; number of electrolyte determinations; number of blood gases; number of units of blood transfused; ICU and hospital mortality rates in the presence of complications, including: respiratory distress syndrome, renal failure, congestive heart failure, coma, requirement of cardiopulmonary resuscitation, and others. RESULTS: The APACHE II score was statistically associated with each intervention and outcome variable tested. Unfortunately, the associations, although consistent, were weak with r2 values ranging from .03 to a maximum of .22 for Pearson's correlation coefficients. CONCLUSION: The APACHE II score was statistically associated with all the variables examined in our surgical patients, but its predictive power for the individual surgical patient was limited. These findings suggest that the score may be useful for retrospective analyses of large cohorts of patients but should not be used as a triage tool or as a predictor of outcome for the individual patient. Triage decisions should continue to be based on the best available clinical judgment. PMID- 1860332 TI - Reduced alveolar macrophage production of tumor necrosis factor during sepsis in mice and men. AB - BACKGROUND AND METHODS: Tumor necrosis factor (TNF) has been implicated as a major humoral mediator of sepsis and endotoxin shock. TNF is secreted by cells of the reticuloendothelial system, including alveolar macrophages. Alveolar macrophage TNF production has been postulated to play a pathogenetic role in the development of adult respiratory distress syndrome (ARDS) in sepsis. To evaluate alveolar macrophage production of TNF during sepsis and endotoxin shock, we studied the effects of sepsis and/or in vivo lipopolysaccharide on the in vitro production of TNF by pulmonary alveolar macrophages. Human pulmonary alveolar macrophages were obtained by bronchoalveolar lavage from six septic and five nonseptic patients, cultured in the presence or absence of lipopolysaccharide (1 ng/mL), and assayed for TNF activity in a bioassay using fibroblast lysis. A murine model of sepsis was also utilized to study pulmonary alveolar macrophage TNF production under more controlled conditions. Normal mice were given ip injections of either lipopolysaccharide or saline. After 2 hrs, pulmonary alveolar macrophages were obtained and cultured in saline or various concentrations of lipopolysaccharide (0.001 to 10 micrograms/mL). RESULTS: There was no difference in baseline TNF activity, expressed as per cent lysis at 1:10 dilution, between pulmonary alveolar macrophages from control and septic patients (35.7 +/- 5.5% vs. 24.4 +/- 9.3%, respectively) (p greater than .05). However, when stimulated with lipopolysaccharide in vitro, the pulmonary alveolar macrophages from nonseptic patients produced significantly (p less than .01) more TNF (82.8 +/- 3.6%) than did pulmonary alveolar macrophages from patients with the septic syndrome (35.2 +/- 3.8%). Similar findings were obtained using the murine sepsis model. The baseline TNF activity in pulmonary alveolar macrophages from control mice was 22.9 +/- 7.0% (mean +/- SEM) and from lipopolysaccharide injected mice was 26.8 +/- 3.3% (p greater than .05). Stimulation with 1 ng/mL lipopolysaccharide in vitro produced an increase in TNF activity in both groups, but the increase was greater in the control mice (68.1 +/- 5.7%) than in the lipopolysaccharide-injected mice (47.5 +/- 5.3%) (p less than .01). When the murine pulmonary alveolar macrophages were stimulated with higher concentrations of lipopolysaccharide (0.1 to 10 micrograms/mL), pulmonary alveolar macrophages from lipopolysaccharide-injected mice produced less than 25.5% of the TNF produced by pulmonary alveolar macrophages from control mice. CONCLUSIONS: These studies indicate that sepsis and endotoxin injection result in a rapid decrease in the ability of pulmonary alveolar macrophages from both humans and mice to produce and secrete TNF in response to lipopolysaccharide. We speculate that a downregulation of TNF production or of macrophage responsiveness to lipopolysaccharide has occurred. These results suggest that sustained TNF production by macrophages is not required for lung injury in sepsis. PMID- 1860333 TI - Operation Desert Shield experience. PMID- 1860334 TI - Administration of angiotensin II in refractory septic shock. PMID- 1860335 TI - Cardiovascular and metabolic responses to red blood cell transfusion. PMID- 1860336 TI - Red blood cell transfusion effect. PMID- 1860337 TI - Methadone treatment in the pediatric intensive care unit. PMID- 1860338 TI - Transurethral prostate resection syndrome. PMID- 1860339 TI - Sepsis-related "cardiogenic" shock? PMID- 1860340 TI - "Sepsis"--clarity of existing terminology ... or more confusion? PMID- 1860341 TI - Use of aminoglycosides in critically ill patients. PMID- 1860343 TI - Pediatric brain tumors. PMID- 1860342 TI - New developments in pediatric nephrology. PMID- 1860344 TI - Neonatal cranial ultrasonography. AB - We trace the evolution of pediatric cranial sonography from its inception to the present. Technical considerations and Doppler imaging are discussed. Scanning techniques and a review of the sonographic landmarks of normal anatomy are presented. Knowledge of these landmarks will facilitate screening examinations. We then present clinical and screening indications for cranial sonography in the neonate, emphasizing the pathogenesis and classification of intracranial hemorrhage and porencephaly. Finally a description of inflammatory lesions and their sonographic appearances and a review of cystic and solid lesions completes the discussion of cranial sonography in the neonate. PMID- 1860345 TI - [Etiopathology and treatment of oral aphthae]. PMID- 1860346 TI - [From Vosges to the Carpathians]. PMID- 1860347 TI - [Mucogingival surgery for the totally edentulous]. PMID- 1860348 TI - [First aid for severely injured patients in mass accidents]. PMID- 1860349 TI - [Clinical management problems in mass accidents]. PMID- 1860350 TI - [Mass accidents from the anesthesiologic viewpoint]. PMID- 1860351 TI - [Unilateral lung transplantation as an effective therapy in primary lung emphysema]. AB - Unilateral lung transplantation is the treatment of choice for terminal restrictive lung disease. We report about three patients with end-stage pulmonary emphysema treated by single lung transplantation. All patients are alive 3, 6 and 7 months after the operation with good quality of life. Blood gases have normalized and lung function parameters have markedly improved. We conclude, that single lung transplantation can be an effective treatment for selected patients with end-stage obstructive lung diseases in the absence of chronic infections. PMID- 1860352 TI - [Carcinoid tumor of the stomach--aspects of surgical therapy]. AB - Carcinoid tumors of the stomach are rare (0.4% of all malignancies of the stomach). Long-lasting hypergastrinemia, most often due to chronic atrophic gastritis, leads to hyperplasia of ECL-cells in the gastric fundic mucosa with consequent dysplasia or neoplasia. Between 1974 and 1988 four patients underwent surgical treatment after diagnosis of a gastric carcinoid tumor. One patient was treated by local excision, two by subtotal resection and one patient underwent complete gastrectomy. None of the patients had local or distant metastases or died in the follow-up period due to tumor progression. The different approaches to surgical therapy are discussed. PMID- 1860353 TI - [Current problems of neuroendocrine tumors of the stomach. Also a comment on the preceding contribution by M. Storck et al]. PMID- 1860355 TI - [Enterostomy in Crohn disease]. AB - Indications, technique and prognosis of 129 enterostomies in Crohn's disease are reported. Advanced perianal or entero-genital fistulas represented the predominant indication (60% of primary, 46% of repeated stomas). 85% of stomas were created in combination with intestinal resections. Preferred type of stoma was a loopileostomy (76% of primary stomas), whereas colostomies were avoided whenever possible because of increased complications. Patients initially presenting with rectal involvement or perianal fistulas were prone to need a stoma during the course of their disease while intraabdominal fistulas, abscesses, age, sex, and longstanding disease where of no prognostic significance. Up to now 50% of all temporary stomas and a third of those created for distal fistulas could be closed. The chance of closure increased significantly with duration of symptoms less than 7 years, not more than one previous operation or absence of rectal involvement. PMID- 1860354 TI - [Effect of reconstruction method on nutritional status after gastrectomy. Comparison of Roux-Y esophagojejunostomy and jejunum interposition]. AB - Body composition, postprandial symptoms and social performance were studied in 61 tumor-free patients after total gastrectomy and Roux-Y esophagojejunostomy (n = 30) or jejunal interposition (n = 31). Emptying of the gastric substitute and small bowel transit of a 99mTc-labeled solid test meal were measured by scintigraphy. Serum glucose levels, and immunoreactive insulin were measured simultaneously. The lowest postoperative weight was 73 +/- 2% of the pre-morbid weight in Roux-Y cases, and 77 +/- 2% after jejunal interposition, the weight at study was 82 +/- 2% respectively 87 +/- 1% of the premorbid weight (p less than 0.05). Of the patients younger than 60 years at operation only one third of the twelve Roux-Y cases had resumed their work, as compared to two thirds of the eighteen interposition cases (p = 0.056). The incidences of the postprandial symptoms were not different among the modes of reconstruction, except for a slightly higher incidence of late dumping in Roux-Y (17% vs. 10%). After correction for gender higher mean values of fat-free mass, total body water, and intracellular water were measured in interposition cases (bioelectric impedance analysis). The emptying half-time of the gastric substitute was 488 s in the Roux Y group, and 378 s after interposition (p = 0.05), whereas the small bowel transit (median: 200 min) showed no differences between the groups. There was no correlation between t1/2 or small bowel transit and the nutritional data. Early dumping (p = 0.01) was the only symptom significantly associated with rapid emptying of the gastric substitute.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860356 TI - [Long-term results after neurolysis and palmar transposition of the ulnar nerve]. AB - We reviewed 41 patients with 43 proximal ulnar nerve compression syndromes. The usual procedure was neurolysis of the ulnar nerve und subcutaneous transposition. The average follow-up period was 5 1/2 years (15 1/4 years to 3 months). The M/F ratio is 2.4:1. Most of the patients are hard manual workers, the dominant arm is most often affected, and 60% have some form of an injury in their history. About half of the patients followed-up have extensive relief of pain, loss of sensibility and weakness of the hand. But only 8 patients feel to have a perfect result. A few do complain of some tenderness in the scar region, some sensibility loss and a Tinel sign along the anterior route of the transposed nerve. Regaining of strength last months or even years. There is a general tendency to better final results in younger patients. PMID- 1860357 TI - [Pancreatic penetration of antibiotics]. AB - Antibiotic therapy is indicated in acute pancreatitis because the most common complication and the mean reason for mortality is a bacterial infection. Concentrations of nine antibiotics from various classes were studied in the pancreatic tissue and pancreatic juice of patients and dogs. The volume of distribution is the most valuable parameter for predicting the potential pancreatic penetration of a substance. As a result of our pharmacokinetic studies mezlocillin and cefotiam, especially ciprofloxacin, have the most antiinfectious potential in treatment of acute pancreatitis. Metronidazole is suitable for combination in cases of pancreatic infections covering anaerobic bacteria. PMID- 1860358 TI - [Technique of microvascular jejunum transfer for replacement of the cervical esophagus]. AB - Technique and results of the first 10 free jejunal grafts after pharyngolaryngectomy are presented. End-to-side venous anastomosis and end-to side pharyngojejunostomy instead of end-to-end techniques are proposed. Hospital mortality was 0 and as minor complications 1 uncomplicated fistula of the proximal and 1 stenosis of the distal anastomosis along with 1 wound infection were seen. There were no vascular complications and no graft loss. All patients were able to swallow and to eat thus an excellent quality of life was achieved. PMID- 1860359 TI - [Leiomyosarcoma of the infra-hepatic vena cava--vascular replacement by expanded PTFE prosthesis with hypothermia of the liver]. PMID- 1860360 TI - [Aneurysm of the persistent sciatic artery]. PMID- 1860361 TI - [Subserous lipoma as a cause of ileo-ileal invagination of the small intestine]. PMID- 1860362 TI - [Measuring bone healing in osteosynthesis with external fixator using the Fraktometer FM 100]. PMID- 1860363 TI - [Comments on the contribution by H. G. Rau et al.: Cutting with the water jet (jet cutting)--an alternative to the ultrasound aspirator?]. PMID- 1860364 TI - [Appendicitis]. PMID- 1860365 TI - [Pathological observations on fallopian tubes after sterilization]. AB - From animal experiments and clinical observation of 130 cases of tubal anastomosis, it has shown that the dilatation of salpinx and adhesion of pelvic organs may occur after ligation of oviduct tube. The present study showed that: (1) tubal dilatation is the result of simple hydrosalpinx and is related to inadequate location of tubal ligation; (2) the mechanical stimulus caused by rough ligation end and large scar is an important factor in producing adhesion of pelvic organs; (3) delicate and gentle operation and choosing isthmus portion to ligate is helpful in prevention of the above changes. PMID- 1860366 TI - [Origin and enrichment of fetal cells in the blood of pregnant women and its uses in prenatal diagnosis]. PMID- 1860367 TI - [National epidemiological investigation of pregnancy induced-hypertension]. AB - An epidemiological investigation of Pregnancy Induced Hypertension (PIH) in a population of 3.7 millions in China is reported in this paper. The incidence of PIH was 9.4%; that of mild moderate-PIH, pre-eclampsia, eclampsia and chronic hypertension with PIH were 4.7, 2.6, 1.7, 0.2 and 0.2% respectively. The maternal and perinatal mortality of PIH groups were higher than the group without PIH (P less than 0.01). Our results revealed that pathogenesis of PIH was positively related to age. Primiparity, multiple pregnancy, labour posture during pregnancy, physical labor intensity, maternal education level, body status, heredity and various complications during pregnancy. PMID- 1860368 TI - [Clinical evaluation of antepartum vibratory acoustic stimulation test]. AB - A prospective comparative study between antepartum vibratory acoustic stimulation test (VAS-T) and nonstress test (NST) was done in 103 pregnant women. Of the 103 cases, 101 of VAS-Ts were positive and 2 negative, with no false negative result. 76 of NSTs were positive and 27 NSTs were negative, with 26 false negative result. The mean duration of VAS-T was 56 seconds. It showed that VAS-T as an effective antepartum monitoring test was safe and much less time consuming. As compared with NST, the false negative rate of VAS-T was reduced, thus the predictive value of negative VAS-T increased. A positive VAS-T predicts with high precision that the fetal well-being is satisfactory, while a negative VAS-T prognostic that the fetal outcome is poor. PMID- 1860369 TI - [Echocardiographic detection of fetal cardiac arrhythmias]. AB - Using real-time directed M-mode and Doppler echocardiography we identified cardiac arrhythmias in 10 fetuses. One had signal tachycardia, one bradycardia, 5 supraventricular premature contractions, and 2 ventricular premature contractions (VPC), which were all self-limited. The diagnosis of VPC in one case was based on premature ending of foramen ovale flap's 2 nd wave on M-mode recording. All cases carried a favorable prognosis except the one with VPC who had a small ventricular septal defect overlooked prenatally. The 10 th case had II degrees atrioventricular block complicated by heart failure and died in utero. This study showed that most arrhythmias can be detected antenatally by analysing atrioventricular contraction sequences. It also proved that the characteristic M mode pattern of foramen ovale flap is of value in evaluating the types of arrhythmias. PMID- 1860370 TI - [Relation between abnormal pregnancies and Toxoplasma gondii infection]. AB - 3,012 pregnant women were divided into three groups according to the status of Toxoplasma gondii infection, and the pregnancy outcomes were followed up. Results showed that the total incidence rates of spontaneous abortion, premature birth, still birth and congenital defects were 0.70, 3.39, 0.83 and 0.90% respectively. The incidence rates of the four groups of abnormal pregnancies having serologically diagnosed recent or active infection were significantly higher than that having no evidence of infection. The relative risk estimates (ORmh) of the 4 groups were 7.01, 3.44, 8.76 and 9.34% respectively. The incidence rates of the groups diagnosed as having past infection were not significantly different from that having no evidence of infection. Analysis of the time lapse from positive serodiagnosis to the appearance of abnormal pregnancies showed that the development of congenital defects was statistically related with Toxoplasma gondii infection in the first trimester of gestation. PMID- 1860371 TI - [Pathological analysis and etiological study on uterine leiomyoma]. AB - The morphologic observations of uterine leiomyoma in 100 cases and the histogenetic study on the uterine muscles of three-month to full-term fetuses in 14 cases have been made. It is found that there exists a transitional feature of perithelial cells, which probably are the cellular anlagen of hysteromyoma and uterine smooth muscle of fetus. Those cells are similar to the fifth month fetal uterine wall cells and might belong to the rudimentary mullerian tissue. Histologically, the hysteromyoma could be divided into five cellular types: mature cell type, proliferative cell type, blastocyte type, retrogressional cell type and mixed cell type. The blastocyte type might be related to an elevated level of estrogen and 59% of retrogressional cell type occurs in the patients above 50 years old. PMID- 1860372 TI - [N2 laser in diagnosis of early cervical cancer]. AB - Two-hundred and thirty-three cases of severe cervical erosion with positive or doubtful Pap smear or atypical cervical proliferation were examined by N2 laser stimulating intrinsic fluorescence method in order to detect early cervical cancer and precancerous lesions. This diagnosis can be made by the fluorescence color or by drawing a curve in a dark room. The correspondent rate to pathological findings was 100% for cervical cancer and 93.9% for cervical dysplasia. PMID- 1860373 TI - [Autoimmune reaction factors of infertility in patients with endometriosis]. AB - The presence of immunoprotein depositions in endometrium and antiendometrial autoantibodies in serum was detected in 59 infertile patients with endometriosis, 45 infertile patients without endometriosis and 11 fertile women by the methods of immunohistochemistry determination and immunodiffusion assay. The immunoprotein depositions in endometrium of endometriosis were significantly increased. The antiendometrial auto-antibodies in serum were positive in 32.2% for infertile patients with endometriosis, 6.7% for infertile patients without endometriosis and 0% for fertile women. This suggested that an autoimmune response might be an etiologic factor of infertility in patients with endometriosis. PMID- 1860374 TI - Coming to grips with a complex matter. A multidisciplinary approach to the synaptonemal complex. AB - Research into the synaptonemal complex (SC) is currently finding renewed interest. This is because the primarily cytological knowledge of the SC has been increasingly supplemented by immunochemical characterization and genetical studies over recent years. Moreover, yeast, offering one of the most handy and rewarding experimental systems, has joined the group of organisms in which the SC can be studied cytologically. In this essay I shall present aspects concerning the SC and its role in meiotic pairing that have emerged over the past few years, parts of which were discussed at a recent meeting in Obertraun, Austria. PMID- 1860375 TI - Fertile male mice with three sex chromosomes: evidence that infertility in XYY male mice is an effect of two Y chromosomes. AB - In the mouse XYY males are sterile, presumably because pairing abnormalities resulting from the presence of three sex chromosomes lead to meiotic breakdown. We have produced male mice, designated XYY*X, that have three sex chromosomes pairing regions but only one intact Y chromosome. Unexpectedly XYY*X, males are fertile, although they are no more efficient in sex chromosome pairing than previously reported XYY males. We conclude that the sterility of XYY males is caused by a combination of the deleterious effect of two Y chromosomes, presumably acting prior to meiosis, and pairing abnormalities resulting in significant meiotic disruption. PMID- 1860376 TI - The Adh in Drosophila: chromosomal location and restriction analysis in species with different phylogenetic relationships. AB - Restriction analysis of the genomic region containing the Adh gene and in situ hybridization assays were performed in six Drosophila species belonging to three different subgenera: D. ambigua, D. subobscura, D. madeirensis and D. guanche (sg. Sophophora); D. immigrans (sg. Drosophila); and D. lebanonensis (sg. Pholadoris). In agreement with previous observations, comparison of restriction maps of the Adh region shows that D. subobscura and D. madeirensis are very closely related. Partial homology is also observed with the rest of the obscura group species. Nevertheless, no resemblance at the restriction map level is detected when more distantly related species are compared. In D. ambigua, D. immigrans and D. lebanonensis in situ hybridization assays reveal a single chromosomal location for Adh, which in D. lebanonensis appears to be sex linked. In contrast, in D. subobscura, D. madeirensis and D. guanche multiple sites of hybridization with homologous and heterologous probes are observed. For example, in D. subobscura and D. madeirensis the functional Adh gene is located on the U chromosome and additional homologous retrosequences are found on the E chromosome. PMID- 1860377 TI - Localization of specific repetitive DNA sequences in individual rice chromosomes. AB - This paper describes the characterization and chromosomal distribution of three different rice (Oryza sativa) repetitive DNA sequences. The three sequences were characterized by sequence analysis, which gave 355, 498 and 756 bp for the length of the repeat unit in Os48, OsG3-498 and OsG5-756, respectively. Copy number determination by quantitative DNA slot-blot hybridization analysis showed 4000, 1080 and 920 copies, respectively, per haploid rice genome for the three sequences. In situ DNA hybridization analysis revealed that 95% of the silver grains detected with the Os48 probe were localized to euchromatic ends of seven long arms and one short arm out of the 12 rice chromosomes. For the OsG3-498 repetitive sequence, the majority of silver grains (58%) were also clustered at the same chromosomal ends as that of Os48. The minority (28%) of silver grains were located at heterochromatic short arms and centromeric regions. For the OsG5 756 repetitive sequence, 81% of the silver grains labeled the heterochromatic short arms and regions flanking all of the 12 centromeres. Thus, each of these three repetitive sequences was distributed at specific defined chromosomal locations rather than randomly at many chromosomal locations. The approximate copy number of a given repetitive DNA sequence at any specific chromosomal location was calculated by combining the information from in situ DNA hybridization analysis and the total copy number as determined by DNA slot-blot hybridization. PMID- 1860379 TI - [Changes in lipid peroxides and superoxide dismutase as incubation of in vitro erythrocytes with cerebrospinal fluids and the action of various scavengers of free radicals]. AB - In this experiment, LPO increased and SOD reduced as the time pass when erythrocytes (RBC) and CSF were mixed and incubated. There was a negative relationship between LPO and SOD. LPO in RBC of arterial blood was higher than that of venous blood after incubation for 3 days (P less than 0.01). When arterial RBCs were incubated together with various scavengers of free radical (SOD catalase and histidine and mannitol), the production of LPO was less than that of arterial RBC incubation singly (P less than 0.01). The change of LPO was not reduced when sodium nitrite and arterial RBC incubated. The results demonstrated that the scavengers of free radicals could be eliminated free radical but failed with sodium nitrite. PMID- 1860378 TI - Chromatin behaviour under influence of puromycin and 6-DMAP at different stages of mouse oocyte maturation. AB - Preovulatory mouse oocytes were cultured in vitro up to each subsequent stages of maturation: germinal vesicle (GV), germinal vesicle breakdown (GVBD), groups of not yet individualized bivalents, circular bivalents, late prometaphase I, metaphase I, anaphase I and telophase I. The stages were identified in living oocytes by fluorescence microscopy using Hoechst 33342 as a specific vital dye. Oocytes from each stage of development developed in vitro and ovulated metaphase II oocytes were subsequently cultured in the presence of puromycin or 6 dimethylaminopurine (6-DMAP), an inhibitor of protein phosphorylation. The effects on chromatin of these drugs were studied during and at the end of culture by fluorescence and electron microscopy. We found that puromycin and 6-DMAP stop meiosis when applied at all stages of oocyte maturation, except for metaphase II. Oocytes at this stage are activated by puromycin. Reaction of the oocytes to the two drugs is different at GV and at metaphase II. All of the other stages react to the drugs by chromatin compaction, which can be followed by chromatin decondensation to form a nucleus. Our results suggest that late prophase chromatin condensation, bivalent individualization and retention of their individuality, as well as individualization of monovalents from telophase and retention of their individuality at metaphase II, are dependent on protein phosphorylation. The events occurring between metaphase I and telophase I are independent of protein synthesis and phosphorylation. The events occurring between metaphase II and formation of the nucleus are independent of protein synthesis. PMID- 1860380 TI - [Olivopontocerebellar atrophy: clinical analysis of 100 cases]. AB - The clinical features in 100 patients suffered from olivopontocerebellar atrophy (OPCA) and their genetic trait were studied. The diagnosis was verified in all cases with computed tomography, demonstrating the atrophy of cerebellum and brainstem, vascular, neoplastic, infectious and any other organic disorder suspected were excluded. 53 out of 100 cases were sporadic (SOPCA) and the remainder (47 cases) was familial (FOPCA). The age of onset in SOPCA group was 36.1 +/- 14.95 (M +/- SD) in average, while in FOPCA group was 28.9 +/- 11.8. It seems that the symptoms in FOPCA group develop earlier than that in SOPCA group (P less than 0.05). All 47 cases of FOPCA group belong to 36 families in which altogether 166 persons were involved. According to pedigree patterns, there were 26 families inherited as autosomal dominant trait and probably so in another 5 families. Autosomal recessive trait could be confirmed in 2 families, in which the parents of proband were consanguineous, and in 3 other families autosomal recessive trait of inheritance was highly suspected. Anticipation was demonstrated in 26 families with dominant inheritance. Generally, ataxia and weakness of legs develop as initial symptoms in 88% of cases, then followed by dysarthria, and ataxia of upper extremities. The rapid alternating test of hand was impaired in 95% of patients, however, tension tremor was revealed only in 53% of patients. A method for assessing the ataxia quantitatively was proposed, our data suggest that the quantitative alternating test in the upper extremity and the measurement of base-width in lower extremity seem to be valuable in identifying the intensity of ataxia. PMID- 1860381 TI - [An epidemiological study of stroke in four areas in Shandong Province]. AB - An epidemiological study of prevalence rate, morbidity rate and mortality was carried out in Jinan. Dongying. Huimin and Zaozhuang among a gross, urban and rural population of 173,630, It was found upon analysis that the prevalence rate of complete stroke was 254.56/100,000 the morbidity rate was 95.03/100,000 and the mortality rate was 59,100,000 Among the four areas, Jinan had the highest prevalence rate and mortality rate of stroke, while they were significantly lower in Zaozhuang as the population there was basically rural. PMID- 1860382 TI - [A testimony procedure of forensic psychiatry used for criminal cases]. AB - A testimony procedure of forensic psychiatry containing of the following steps as: "to set-up the medical diagnosis-to clarify the criminal motive-to determine the property of criminal legal ability damage-to evaluate the criminal responsibility" is recommended, and upon them "to clarify the criminal motive" is of importance. The property of criminal legal ability damage can be determined through the criminal motive and then the degree of criminal responsibility can be evaluated objectively through the criminal motive and criminal legal ability effected by the disease. PMID- 1860383 TI - [A control study of clomipramine and amitriptyline for treating obsessive compulsive disorder]. AB - This paper reported a comparative study of clomipramine (n = 21) and amitriptyline (n = 18) for treatment OCD. The improvement rate of clomipramine and amitriptyline was 95.2% and 55.6%, respectively (P less than 0.01). The decreased scores of obsessive-compulsive and depressive factors of SCL-90 of clomipramine were higher than amitriptyline. The results showed that clomipramine has better therapeutic effects and less side-effects than amitriptyline. PMID- 1860384 TI - [Clinical analysis in the main side effects of clozapine: enclosed 600 cases report]. AB - The main side effects of 7921 hospitalized patients taken clozapine from July in 1980 to October in 1988 were investigated. In these cases, there were 600 patients with the main side effects caused by clozapine. They included 312 patients with leukocytosis (52.0%), 114 patients with leukopenia (19.0%), (included 16 patients with agranulocytosis), 53 patients with EEG abnormal (8.9%), 35 patients with fever (5.9%), 32 patients with EKG abnormal (5.3%), 14 patients with rash (2.3%), 12 patients with epileptic seizure (2.0%), 11 patients with posture hypotension (1.8%), 8 patients with paralytic intestinal obstruction (1.3%), 6 patients with SGPT raised (1.0%) and 3 patients with conscious disturbances (0.5%). The causes and treatments of the main side effects mentioned above were discussed. PMID- 1860385 TI - [A self body double blind clinical study of L-tryptophan and placebo in treated neurosis]. AB - In this paper the authors report the results of a cross-over treatment of 79 case of neurosis with vacuum drugs and L-tryptophan. The therapeutic effects were evaluated respectively with four-degree scale and the rating scales of SCL-90. Sleep vs. Sleep disturbance self-checklist. Side effects were evaluated with TESS. The data show that treatment of L-tryptophan 3.0g/day for six weeks. Rate of marked improvement is 58.2%, effective rate is 91.1%. It is concluded that the effects of hypnosis and sedation are mild side effects only. Using L-tryptophan the therapeutic effects which concern somatization depression anxiety, phobia, compulsion, are analysed and discussed. PMID- 1860386 TI - [A controlled study of clinical therapeutic effects of laser acupuncture for schizophrenia]. AB - A controlled study of clinical therapeutic effects of laser acupuncture was made for 33 patients suffering from schizophrenia. As evaluated by BPRS, CGI, a rating scale for extramidal side effects and chinese clinical assessments for therapeutic effects. Our clinical practise suggests that laser acupuncture was as effective as chlorpromazine in the treatment of schizophrenia. PMID- 1860387 TI - [Bulbar conjunctival microcirculation in schizophrenics]. AB - A comparative observation on bulbar conjunctival microcirculation (BCM) between 38 schizophrenics and 38 normal controls was carried out. The results showed 95% abnormal BCM in schizophrenics. And among them, the moderate and severe abnormal BCM was 74%. And in all of the 14 investigated items, the general abnormalities were 50%. But in normal controls, abnormal BCM was 27%, and just a few of them appeared the general abnormalities, and no one suggested moderate and severe abnormal BCM. As compared the results obtained in schizophrenics with those in normal controls, we found 12 investigated items such as irregularity in diameter, dilatation and tortuosity of tiny vena; irregularity in diameter, stiff of tiny arteria; small hemorrhagic spot, brown pigmentation, red blood cells collected in tiny vena and capillary, small vascular density, speed of blood flow and arterio venous ratio were statistically significant. PMID- 1860388 TI - [Analysis of the cultural and mental diseases rates of the three nationalities from She, Hui and Mongolian peoples]. AB - This paper researches into transcultural psychiatry from She. Hui and Mongolian Nationalities in an epidemiological fact-finding way. Its results show that different historical cultural background geographical environment and custom of these three nationalities closely related to mental health including the sickness rates the symptoms and the kinds of mental disease. PMID- 1860389 TI - [A prospective controlled study of psychosomatic and immunologic change in recently bereaved people]. AB - This research was carried out in 45 bereaved people who were the close relatives of a bus accident victims. Their mental and physical conditions, IgA, IgG, IgM, C3 and C4 levels were measured. It reveals that mental and physical conditions of the investigated group declined and the incidence of infectious diseases increased in comparison with the control group. Subjects antibody and complement functions were inhibited after bereavement. The social support they perceived functions in the way of buffering the stress as well as improving the immunity. PMID- 1860390 TI - [Relation between the clinical manifestations and electromyographic findings in motor neurone disease]. AB - 343 cases of motor neurone disease (MND) were examined with electromyography. The result showed EMG examination was of much vale in helping to ascertain an accurate diagnosis which clinically could be made in only about 1/4 of the series of cases. The ages of onset ranged from 4 months to 10 years with an average of 36.8 years. 56.8% under 40 years. There was a higher male preponderance, the male/female ratio being 3.2:1. It was 1.6:1 in a report from a western country. 123 cases showed only one limb involvement clinically while the EMG findings were also abnormal in the other three limbs. Fibrillation potentials were found to be at more than two sites in one muscle in 84.5% in this series, where as they occurred in 95-100% of the infantile and juvenile cases. Abundant fibrillation potentials were found in 37.1% of the cases within 3 years after the onset and in 13.6% in those with a longer duration. The increment of the mean duration of motor unit potential was 94.5% and that of the mean amplitude 91%. It seemed not necessary to emphasize giant potentials. The motor nerve conduction velocities (NCV) were normal in 95% while the sensory NCV were almost always normal (98%). All of the 3 cases tested with single fiber EMG showed an increment of jitter of 95-100% and a muscle fiber density of 2.95-3.65. PMID- 1860391 TI - [The clinical significance of multifactor discrimination and analysis of maternal serum Cu, Zn, Cd, Mn contents in the diagnosis of abnormal fetus]. AB - In this paper we present pair-comparison test with serum contents of Cu, Zn, Cd, Mn, Se in pregnant women with neural tube defects fetus (NTD), pregnant women with normal fetus and healthy with no pregnancy using Bayes Stepwise Discrimination Analysis and Fisher Discrimination Analysis. The results showed: NTD of fetus was related to deficiency of maternal serum in Cu, Zn, Mn and to excess of Cd. The maternal serum levels of Cu, Cd and Mn can be used as sensitive indicator to detect intrauterine abnormality at an early stage. The low levels of maternal serum in Zn and Se were not a specific indicator of NTD but a characteristic shared by all pregnant women. It is important to pay attention to supplying pregnant women at an early stage with Zn, Se to meet the needs of normal growth of the fetus and prevent foetal abnormality. With stepwise discrimination we established two equations by Cu, Zn, Cd, Mn used for distinguishing normal from abnormal fetus. The accordant rate of clinical discrimination with classification output for inside examples was 93%. In the equation established by Fisher principle Mn had the greatest rate, namely, 37.6%. PMID- 1860392 TI - [Study on mutagenicity of size-fractionated air particles]. AB - Ames Salmonella assay and sister chromatid exchanges in CHO cells were used to study the mutagenic activity of size-fractionated air particles from outdoor air in Beijing, Taiyuan, Wuhan, Shenyang and the areas with high incidence of lung cancer in Xuanwei county. Five size particles were collected from each sampling points. The results indicate that: 1. The results of organic matter content in particles. 2. All of the samples have mutagenicity. There was negative correlation between mutagenicity and particle sizes, mutagenicity was increased with particle size reduced. The maximum mutagenicity was at the particle size less than 1.1 microns. So it is especially hazardous to human health. There was logarithmic correlation between organic matter content and revertants. Correlation coefficient was 0.98. Regression equation was gamma = 0.23 + 1.01 X. 3. The results showed that of the five sampling points air pollution at the high lung cancer incidence area of Xuanwei county was the most severe. PMID- 1860393 TI - [Preliminary study on sanitary standard of aluminium in drinking water]. AB - Sanitary standard of aluminium in drinking water is not formulated in China. In this paper safe maximal dose of aluminium in drinking water was studied, using acute and chronic toxicological experiments, cytogenetic toxicological assays and sensation threshold tests of AlCl3 and Al3(SO4)3. Considering with available epidemiological information, a preliminary sanitary standard of aluminium in drinking water 0.2 mg/L is recommended. PMID- 1860394 TI - [Epidemiological interventional study on controlling endemic arsenism]. AB - Residents exposed to high arsenical water in Kuitum area of Xinjiang Autonomous Region were studied by on the spot interventional trial experiment. After ridding arsenic from drinking water, 82.43% of chronic arsenism were either cured or showed improvements of health conditions and no new' cases of arsenism developed during the experiment. The values of arsenic in patiens hair and urine decreased by drinking water free of arsenic, but remained higher than those of normal residents. Our results showed that drinking normal water could help to progressively eliminate arsenic storage from the chronic arsenism. By means of electromyograph (EMG), we found that the nerve conduction velocities of patients increased significantly (P less than 0.01) and that -SH reactivities of peripheral blood corpuscles of patients recovered to the normal level. PMID- 1860395 TI - [Exposure levels and biological monitoring of pyrethroids in spraymen]. AB - In order to assess the exposure levels of pyrethroids in spraymen, 50 adult male cotton growers were selected as monitoring subjects. The exposure levels were evaluated by measuring the air concentration, dermal exposure and urinary content of pyrethroids. The results showed that the air concentrations of deltamethrin at breathing zone were 0.02-0.32 micrograms/m3 in deltamethrin exposed group, and of fenvalerate at 0.69-1.09 micrograms/m3 in exposed spraymen. The dermal exposure was more prominent and indicated the most significant route of absorption. In one day spraying, the urinary deltamethrin was not detected at 12 hours after the beginning of exposure while the fenvalerate was still detected 24 hours after starting exposure. However, both can be consecutively detected even two days after cessation of a three-day spraying. Health effects were investigated by interviews and physical examination. 32 out of 50 spraymen at the above exposure levels complained of abnormal facial sensations. No acute pyrethroid poisoning cases were found. PMID- 1860396 TI - [Influence on benzene and toluene to reproductive function of female workers in leathershoe-making industry]. AB - The reproductive function of 223 women exposed to benzene and toluene was studied against 327 controls. The results showed: the incidence rate of menstrual disorder in the exposed group was 48.88%, significantly higher than that in the control group (16.21%), the incidence rates of menstrual-blood anomaly and dysmenorrhea had a tendency to increase with the length of employment. The incidence rates of spontaneous abortion and gestosis in the exposed group were 5.7% and 22.6%, distinctly higher than those in the control group (2.4% and 10.5%); The difference of the above mentioned indices were statistically significant between the two groups, indicating that both benzene and toluene had a deletions effect on the reproductive function of the female workers. PMID- 1860397 TI - [An analysis of the occupational trauma cases in Beijing Changping County, 1980 1986]. AB - An analysis of the occupational trauma cases in 8 enterprises of Changping county showed that the over-all trauma rate was higher among the workers of the mechanic process (3.85%). The trauma cases among the mechanical workers were 74.2% of the total trauma cases. The common site of trauma was the four limbs (75.0-82.0%). The trauma occurred more frequently in the last two hours of the 8 working hours (205/438, 46.8%). A statistical analysis on the periods of three curves of the body bio-rhythm (e.g; physical, sentiments and intelligence curves) revealed close relationship between the occupational trauma and the period of the body bio rhythm. PMID- 1860398 TI - [Comparison of somatotype between Chinese and Japanese children and youth by using Heath-Carter method]. AB - This study was designed to compare the different somatotype growth of Chinese and Japanese boys aged 7 through 17. 2,074 subjects participated in it. Their somatotypes were analysed by using Heath-Carter method and their morphological varieties compared. Significant differences were found not only in their limb length and bone width, but also in their muscle circumferences and skinfolds. These differences showed the superiority of Chinese boys in ectomorph factor and the Japanese boys in endomorph and mesomorph factors respectively. The somatotype distributions of these two nations were also quite different at different ages, although they showed similar changing trend of somatotype around adolescent growth spurt. PMID- 1860399 TI - [The measurement of visual refraction of pupils]. AB - The ocular refraction was measured by applying 1% atropine eye-drops for 3 days in 5,458 eyes (male 2,944, female 2,514) of the pupils aged 7-17 in rural areas. The results were as follows: the majority of the pupils had hyperopia (male 84.71%, female 80.55%); the frequency of the measurements was not in normal distribution; the degree of far-sight began to recede and gradually become converted to myopias with advancing age but varying greatly between age-groups. The myopias began to appear at the age of 9 and increased rapidly at the age of 14 for girls and 15 for boys. From then on the rate of conversion continued to increase with schoolgirls more than schoolboys and, as a result, formed "the dangerous stage of myopia", the values of physiological visual refraction were shown as follows: pupils aged 7-9 + 2.00 D- + 2.50 D, aged 10-13 + 1.50 D- + 1.75 D, aged 14-17 + 1.00 D- + 1.25 D. The possibility of pathological hyperopia was greater if the pupils aged 7-9 and the value of visual refraction over +3.75 D, aged 10-13 had the value over +3.00 D and aged 14-17 had the value +2.50 D. The possibility of developing myopia was great in those pupils aged 7-9 whose value was under +1.00 D and in those aged 10-17 whose value was under +0.50 D. The deprived vision of the pupils should be routinely corrected by skiascopy. PMID- 1860400 TI - [Reversion of eye position after surgical correction of exotropia]. AB - The authors analysed the reversion of eye position in 62 postoperative patients of concomitant exotropia. The results indicated the presence of a correlation with the preoperative condition of binocular vision, the type of strabismus, and the age of patient. The authors opened that the amplitude of surgical correction should depend on these factors, and prudence should be exercised in recommending surgical intervention for mild intermittent exotropia in children. PMID- 1860401 TI - [Binocular vision of concomitant esotropia after surgical correction]. AB - Binocular vision of grade I or better was restored to 51.5% of 312 cases of concomitant esotropia after surgical correction. Cases of acquired, partially accommodative, and small-angle esotropia had better chances of restoration than did cases of congenital, non-accommodative, and large-angle esotropia (P less than 0.01), as were younger patients (less than 12 years) with satisfactory surgical correction than older patients with less satisfactory surgical correction. Factors that affected restoration of binocular single vision were discussed. PMID- 1860402 TI - [Correction of complete blepharoptosis with suspension by Frontalis aponeurosis flap]. AB - The surgical corrective result of complete blepharoptosis is often uncertain. With suspension by Frontalis aponeurosis flap under the brow, the author treated 73 cases satisfactorily, the results conforming to Fox's criteria of a normal eyelid. The incision is made in the skin and Orbicularis oculi at the double-fold of the eyelid, and a muscle flap 2 cm wide is separated from under the Orbicularis oculi at the brow in the conjunction of Orbicularis oculi and Frontalis. The flap is fixed to the tarsus, and a strip of redundant skin 2-3 mm wide excised. The incision is closed with intermittent sutures. PMID- 1860403 TI - [Experimental study of the inhibitory effect of daunorubicin and doxorubicin in conjunctival fibroblast proliferation]. AB - Both daunorubicin and doxorubicin were found effective in inhibiting proliferation of rabbit conjunctival fibroblasts in vitro. The 50% inhibition dose for daunorubicin was 0.14 micrograms/ml, and 0.46 micrograms/ml for doxorubicin, the former being stronger. The authors were hopeful that these drugs would prove useful in preventing cicatrization after glaucoma filter surgery. PMID- 1860404 TI - [Ofloxacin content in tears following topical use of 0.3% ointment]. AB - Tear and aqueous humor levels of ofloxacin following 40mg of topical 0.3% ointment were determined at intervals within 24 hours by high performance liquid chromatography. The highest tear level was detected in half an hour, and effective concentrations existed in 6 hours. The highest aqueous humor level was detected 60 minutes after administration. Ofloxacin ointment produced higher tear concentrations for longer time than did aqueous solution of the drug. PMID- 1860405 TI - [Chlamydia trachomatis immunotypes in trachoma epidemic areas of north China]. AB - The distribution of various immunotypes of C. trachomatis in epidemic areas of North China was studied by the micro-immunofluorescence (Micro-IF) test of tears and sera from 104 patients with trachoma. IgG antibody to C. trachomatis was positive in 64 cases, and the immunotypes were type B (78.1%) and type C (21.9%). The TE-55 strain determined as type I in 1966 was confirmed to be type C. The Micro-IF test that quantitated antichlamydial IgG antibody in tears was compared with ELISA in the detection of C. trachomatis in 59 individuals. The sensitivity and specificity of the Micro-IF test were 91.5% and 100% respectively. PMID- 1860406 TI - [Histopathologic classification of 1422 orbital tumors]. AB - The authors analyzed 1422 orbital tumors examined 1955-1986 in the eye pathology laboratory. The 5 leading malignant orbital tumors were adenocarcinoma (207 cases), squamous cell carcinoma (135 cases), rhabdomyosarcoma (52 cases), lymphosarcoma (39 cases), and malignant mixed tumor (29 cases). The 5 leading benign orbital tumors were cavernous hemangioma (304 cases), benign mixed tumor (109 cases), inflammatory pseudo-tumor of the orbit (101 cases), dermoid cyst (100 cases), and optic meningioma (65 cases). Rare tumors of the orbit included 1 case each of alveolar soft tissue sarcoma, chondrosarcoma, mesenchymal chondrosarcoma, synovial sarcoma, giant cell tumor, granular myoblastoma, metastatic leiomyosarcoma of the uterus and metastatic lymphoepithelioma. The criteria for pathological classification and differential diagnosis are discussed. PMID- 1860407 TI - [Clinical significance of Doppler sonography in the diagnosis of anterior ischemic optic neuropathy]. AB - The authors measured the PK (peak frequency with Doppler sonography in 52 patients of anterior ischemic optic neuropathy AION), 16 patients of oculovascular disease (OVD), and 371 normal subjects. The age ranged from 21 to 62 years in the patients, and 10 to 83 years in the normals. The arterial segments examined were of the bilateral common carotid arteries (CCA) and internal carotid arteries (ICA), totalling 272 segments in the patients and 1,484 in the normals, with the findings that the rate of carotid stenosis in AION was higher than in OVD, and carotid stenosis was observed in 75% of CCA and 91% of ICA in patients under the age of 30 years, significantly higher than in elder age groups. This provides a basis for the definite diagnosis of AION in patients under 30 years old. PMID- 1860408 TI - [Clinical application of the ophthalmic high frequency ultrasonic B-scan diagnostic equipment]. AB - 800 eyes were examined with the ophthalmic high frequency ultrasonic B-scan diagnostic equipment. The results were confirmed by medication, optical examination, CT, surgical operation, or pathology at a rate of 93.3%. The authors discussed the acoustic characteristics of the ultrasonic image of common ocular diseases and its functional characteristics. It was believed that the equipment markedly enhanced the diagnostic capability of ultrasound in ophthalmology. PMID- 1860410 TI - [The model PC-A8610C artificial intraocular lens]. AB - The Model PC-A8610C artificial intraocular lens was developed in collaboration with the Institute of Optical Precision Machinery, Academia Sinica, in 1986. From April 1987 to November 1988, the lens was implanted in 80 eyes (73 cases) that were followed up 6-24 months. Corrected visual acuity was 0.5 or over in 90.9% of the patients and complications were few. PMID- 1860409 TI - [Culture of anaerobic bacteria and antibiotic sensitivity test in ocular infectious diseases]. AB - Anaerobes were isolated from 43.9% of 116 eyes with infectious diseases and 21.4% of 140 normal conjunctival sacs. The predominant anaerobes were peptococcus (28.6%) in the former and propionibacterium (53.3%) in the latter. In eyes with infection, only anaerobes were isolated from 27, and a mixture of anaerobes and aerobes in 24. The sensitivity of anaerobes (68 strains) to 10 antibiotics differed significantly from that of aerobes (102 strains). Most anaerobes are sensitive to chloramphenicol and cephaloridine, but not to aminoglycosides or polymyxin B. Therefore, when an ocular infection shows a negative aerobic culture, anaerobic infection should be suspected and chloramphenicol is indicated as first choice for treatment. PMID- 1860411 TI - [Observations on the intraocular pressure after extracapsular cataract extraction]. AB - The author observed the IOP of 32 eyes after extracapsular cataract extraction with posterior chamber intraocular lens implantation. The IOP was elevated in all cases, over 0.67 kPa (5 mmHg) in 22 cases, over 1.33 kPa (10 mmHg) in 12 cases, and the highest was 5.05 kPa (38 mmHg). The peak of elevation was at 24 hours after operation and most cases resumed the preoperative levels in 48 hours. The IOP of eyes with intracameral carbachol was significantly lower than that of those without at 6 hours after operation, but the difference became insignificant after 24 hours. PMID- 1860412 TI - [Treatment of choroidal hemangioma]. AB - Eight (8) cases of choroidal hemangioma, comprising 6 of the solitary type and 2 of the diffuse type, were treated with Argon laser, including 2 cases in combination with cryotherapy. The success rate was 76.5%, with visual acuity improved in 75% of them during an average follow-up of 11.7 months. Tumors with much subretinal fluid were first given cryosurgery before Argon laser treatment for good synergic therapeutic effects. PMID- 1860413 TI - [A clinical and pathological study of 24 cases of primary non-Hodgkin's lymphoma of the orbit]. AB - Primary non-Hodgkin's lymphoma of the orbit predominantly consists of the small lymphocytic, the lympho-plasmacytic, and the schistocytic types. Because of fair cellular differentiation, the tumor shows low or medium atypia as if benign. Hence, differential diagnosis from inflammation pseudotumor or lymphocytic hyperplasia is important. Follow-up of 18 of the present 24 cases showed that the tumor usually began insidiously and was long confined to the orbit. 44% (8/18) of the patients had relapses and 22% (4/18) died of systemic dissemination 2-6 years after confirmed diagnosis, a finding in agreement with Kinyh et al, who reported a 5 year survival rate of 75% and a 8 year survival rate of 50%. The prognosis was better than that of intranodal or extranodal non-Hodgkin's lymphoma in other locations. PMID- 1860414 TI - [The dumb-bell orbital dermoid]. AB - Bony resorption was a characteristic radiogram finding in a series of 25 cases of dumb-bell orbital dermoid, and a definitive diagnosis of the nature and locality of the tumor could be done by ultrasonography, CT, or MRI. In all the 25 cases, the mass was lodged between the orbit and the temporal fossa, the frontal sinus, or the cranial fossa like a dumb-bell. The authors emphasized the use of X-ray, ultrasonography, CT or MRI before operation, and thorough clearance of the cystic and fistula wall with cauterization by carbolic acid was imperative for the prevention of recurrences. PMID- 1860415 TI - Non-random mating between Boophilus microplus and hybrids of B. microplus females and B. annulatus males, and its possible effect on sterile male hybrid control releases. AB - When Boophilus microplus and Type-II hybrids (B. microplus females X B. annulatus males) were released simultaneously onto bovine hosts, mating between the two forms appeared not to be at random. There were more contypic and fewer intertypic matings than predicted under an assumption of panmixia. An examination of the patterns of matings revealed that more of the matings on the first two days of detachment were between the two sexes of B. microplus. Engorged females dropping on the last four days of maximum female detachment were predominantly hybrids mated to both B. microplus and hybrid males. The non-random mating pattern does not appear to be caused by assortative mating between B. microplus and Type-II hybrids, but because the B. microplus were competent to mate two days before the hybrids and the B. microplus males compete for males of both types better than the Type-II males. PMID- 1860416 TI - Spatial distribution of the Karoo paralysis tick Ixodes rubicundus (Acari: Ixodidae) within a false upper Karoo veld type. AB - Spatial distribution of the Karoo paralysis tick (Ixodes rubicundus) has been studied in a paralysis enzootic area of the southwestern Orange Free State. Significantly more females than males were collected from the vegetation. Most ticks (99%) used grass as questing sites at a height of approximately 45 cm (range 10-97 cm), which correlates with the size of host animals. No significant differences between the questing height of male and female ticks were evident. The ticks were found on most of the grass species present and, except for the genus Eragrostis, no specific preference was evident. When questing, the capitulum of I. rubicundus is usually (90%) directed towards the ground. Seventy eight percent of the ticks occurred singly on a specific grassblade or flowerhead. In those cases where two ticks occurred together, no sexual aggregation was evident. Most ticks occurred under or close (mean = 62 cm) to the crown cover of specific shrub or tree species. These plant species were characterized by a dense crown cover with a mat of decaying leaf litter underneath. The preference of the tick for wild olive trees (Olea europaea africana) suggests that, except for the physical characteristics of this tree species, host factors may also be important. Significantly more ticks were distributed on the cooler, more protected southern sides of vegetation in comparison to the northern sides. PMID- 1860417 TI - Endocytobionts in Dermacentor reticulatus ticks (Ixodidae): an electron microscope study. AB - Endocytobionts (ECBs) were detected in the ovaries of Dermacentor reticulatus. Their developmental cycle is directly related to the developmental stages of tick oocytes. Two basic forms of ECBs occur in tick cells, i.e. dense forms, occurring singly or in aggregates situated free in the cytoplasm of host cells, and the light forms which are larger, pleomorphic and always situated inside vacuoles of host cells. The light forms occur together with dense forms in all oocytes. The dense forms occur freely and independently in funicular cells of the oocyte, the epithelial cells of oviducts, and additionally in the cells of the Malpighian tubules. A probable function of ECBs in the tick host is discussed. PMID- 1860418 TI - Role of genital sex pheromones in Amblyomma americanum and A. maculatum (Acari: Ixodidae). AB - Amblyomma americanum and A. maculatum were studied to determine if genital sex pheromones were present, as reported in Dermacentor species. Chemical analysis of methanol extracts of the anterior reproductive tracts (source of the genital sex pheromone) of A. americanum and A. maculatum confirmed the presence of the same fatty acids that act as components of the genital sex pheromone in Dermacentor variabilis and D. andersoni. In both Amblyomma species, removal of the anterior reproductive-tract of fed females eliminated the male copulatory response. For A. americanum, use of anterior reproductive tract extracts made with water, methanol, ether and hexane elicited significant probing and copulatory responses by conspecific males. However, in A. maculatum, use of anterior reproductive tract extracts made with water, methanol, ether, chloroform:methanol (4:1), hexane and pentane did not restore mating response by males. Treatment with known components of Dermacentor genital sex pheromones elicited weak but significant responses in A. americanum, but did not restore male mating responses in A. maculatum. These results indicate that genital sex pheromones exist in A. americanum and are not restricted to the genus Dermacentor. Characteristics of the Amblyomma genital sex pheromone, however, do differ considerably from those in Dermacentor. No genital sex pheromone was present in A. maculatum. PMID- 1860419 TI - [Primary coronary stent implantation in complex morphology of stenosis or unsatisfactory results of angioplasty]. AB - Early and late results of coronary angioplasty are influenced by the morphology of the coronary artery stenosis. Primary implantation of a balloon-expandable Palmaz-Schatz stent was indicated in 37 patients (31 men and 6 women; mean age 57 +/- 2 years) with symptomatic coronary heart disease and complex morphology of the stenosis. Intracoronary stents were successfully placed in 30 of 37 patients, without complications in all but one. This patient developed a thrombotic occlusion of the vessel 3 days after the procedure which, despite high-dosage thrombolysis treatment, resulted in an anterior wall myocardial infarction. A repeat angiography has since been performed (3-7 months after the procedure) in 25 of the 29 patients with a complication-free course. In 19 of the 25 patients the site of implantation was smooth, while a silent re-occlusion had occurred in one after successful recanalization of a chronic occlusion. Two patients had a subtotal restenosis (12% angiographic restenosis rate). These data indicate that intracoronary stent implantation improves the morphological results after balloon dilatation and reduces the restenosis rate. PMID- 1860420 TI - [Long-term results after infrainguinal arterial reconstruction in patients with type 2 diabetes mellitus and without diabetes mellitus]. AB - The influence of type II diabetes on the success rate of arterial bypass operations in the leg was assessed in a prospective study, since 1984, of long term results of infrainguinal arterial reconstruction in 67 type II diabetics (41 men and 26 women; mean age 71.2 [47-90] years) and compared with 133 nondiabetics (90 men and 43 women; mean age 71.5 [45-91] years). All had a bypass for chronic critical ischaemia of the legs. Graft patency, leg preservation and survival rate were calculated and compared by the actuarial method. Coronary heart diseases and cerebral ischaemia were a little more common in the diabetic group, but the incidence of heart failure was the same (20%). A venous bypass was used in 73% of diabetics, polytetrafluoroethylene grafts in 27% (nondiabetics: 79% and 21%). Bypass occlusions occurred in 9 diabetics and in 24 nondiabetics (not significant). During the observation period of 5 years 37 diabetics (55%) and 39 nondiabetics (29%) died (P less than 0.001). These data indicate that the results of infrainguinal arterial bypass operations are equally good in diabetics and nondiabetics. Amputation was avoided in 80% of legs at risk in both groups. Primary amputation is indicated only in exceptional circumstances. PMID- 1860421 TI - [Tryptophan-induced fasciitis-scleroderma-eosinophilia syndrome]. AB - A fasciitis-sclerodermia-eosinophilia syndrome developed in four female patients, aged between 55 and 75 years, after the ingestion of tryptophan, 1.5-6.0 g daily, for 13 months to 7 years. It began characteristically with hard oedema of the limbs, sometimes also of the trunk. Later there occurred diffuse indurations of the body surface with fixation of the skin to fascial planes. This was associated with mainly sensory peripheral neuropathy. Three of the patients had an eosinophilia (12-30%). Histological examination revealed a cell-poor fasciitis, fibrosis of the cutis and subcutis, perimyositis and epidermal atrophy of varying degree. Erythrocyte sedimentation rate was at most slightly increased. Antinuclear antibodies were demonstrated in one patient (1:80). Serum aldolase concentration was raised (3.4-5.4 U/l), while creatine kinase was normal. The disease progressed even after tryptophan was discontinued, in only one patient there was improvement during glucocorticoid treatment. In two cases the skin induration regressed slowly after administration of methotrexate (15 mg weekly) and hydroxychloroquine (400 mg daily). PMID- 1860422 TI - [Tuberculosis of the larynx, oral cavity and pharynx]. AB - A 44-year-old man, a heavy smoker over many years, complained of hoarseness for 8 weeks with weight loss and dysphagia. Malignant tumour of the pharynx was suspected. Examination revealed a swelling of the right upper lip, tumorous changes in the right buccal mucosa, about 6 x 6 cm in size, as well as enlargement of the cervical lymph-nodes. Microlaryngoscopy revealed a three-level tumour of the entire side of the right larynx. Histological examination of biopsies of the right false and true vocal cords as well as the buccal mucosa demonstrated numerous, partly caseous epithelioid granulomas with Langhans giant cells. Ziehl-Neelsen staining showed acid-fast rods. Combined tuberculostatic treatment with isoniazid, rifampicin, ethambutol and pyrazinamide achieved regression of all signs and symptoms within two months. This case emphasizes the need for including laryngeal tuberculosis in the differential diagnosis of seemingly malignant laryngeal tumours. PMID- 1860423 TI - [Insulin-induced edema in adolescents with type 1 diabetes mellitus]. AB - Two girls (aged 14 and 16 years) with type I diabetes were hospitalized with blood sugar levels of 394 and 319 mg/dl as well as HbA1 levels of 14.2 and 14.1%, respectively. In the first case it was the first sign of diabetes, in the other it was the result of a metabolic dysfunction with an injection abscess after ten years of the disease. After an initial substitution with regular insulin (subcutaneously in Case 1 [1.5-1.7 IU/kg daily for 3 days; in Case 2, continuous i.v. infusion [1.3 IU/kg daily] for 58 hours, followed by injections of appropriate mixtures of short and long-acting insulin) serum glucose levels were nearly always within normal range from the third day onward. Within 6 days of normal glucose levels being established hard pitting oedema, especially of the legs, developed in both girls, associated with a weight gain of 6.1 and 7.0 kg, respectively. Renal, hepatic and cardiovascular disease having been excluded the diagnosis of insulin-induced oedema was made. Within a further two weeks the oedema had disappeared without any specific treatment. PMID- 1860425 TI - [Unconstitutionality of the planning for the need of large equipment. Decision of the Baden-Wurttemberg Regional Social Court, 4/24/1991]. PMID- 1860424 TI - [Systemic therapy of cerebral metastases in breast carcinoma]. PMID- 1860426 TI - [Elimination of incorporated nickel]. PMID- 1860427 TI - [Anticoagulation in deep venous thrombosis of the legs]. PMID- 1860428 TI - [Coronary angiography with 5-F-catheters]. PMID- 1860429 TI - Growth and motor development in fetuses of women with type-1 diabetes. II. Emergence of specific movement patterns. AB - In 20 women with type-1 diabetes, the emergence of fetal movement patterns was studied using real-time ultrasound. One-hour recordings were made once a week between the 7th and 17th week of gestation. Data were compared to those obtained in uncomplicated pregnancy. The diabetic women were being treated with continuous subcutaneous insulin infusion (CSII) therapy. Except for breathing movements, there was a 1-2 week delay in the first appearance of all movement patterns which normally emerge during the first 12 weeks of pregnancy. Breathing movements were observed for the first time at an earlier age than in the control fetuses (P less than 0.02). When the emergence of frequently occurring movement patterns was plotted against fetal crown-rump length, which is usually smaller in diabetic pregnancy, there was still a general delay in comparison with the control group. The delay in motor development therefore does not run completely parallel with the delay in growth. This indicates the possible existence of a specific diabetes related influence on the functional development of the embryonic and fetal nervous system. Hyperglycaemia, for example, may be responsible, as the delay in the emergence of fetal general movements was most profound in the women whose periconceptional quality of glucose control was poor. PMID- 1860430 TI - Growth and motor development in fetuses of women with type-1 diabetes. III. First trimester quantity of fetal movement patterns. AB - Delayed emergence of movement patterns and disturbances in the development of behavioural states are often observed in the fetuses of diabetic women. The developmental course of specific fetal movement patterns was studied in 20 women with type-1 diabetes during the first trimester of pregnancy. The aim was to investigate whether maternal diabetes also has an effect on the rate of occurrence and temporal patterning of fetal movements. Real-time ultrasound recordings with a duration of 1 h were made once a week between the 7th and 17th week postmenstrual age in order to quantify fetal movements. The data were compared to those obtained in a group of uncomplicated pregnancies. The developmental trends in the occurrence of movement patterns were similar to those in the control fetuses, with the exception of startles. Before the 9th week of gestation, fetal movements occurred less frequently; this was related to the quality of maternal glucose control. After 12 weeks, the overall incidence was higher than in the control group, due to an increase in the incidence of breathing movements. The rate of breathing movements was generally slower than in the control group. PMID- 1860431 TI - Spontaneous respiratory effort during mechanical ventilation in infants with and without acute respiratory distress. AB - Respiratory interactions of 27 ventilated preterm infants were recorded daily during the first 14 days of life to assess the effect on respiratory efforts of recovery from acute respiratory distress syndrome (RDS). Active expiration and persistent asynchrony only occurred during acute RDS (P less than 0.01). Throughout the 14-day period, in the majority of infants making respiratory efforts, a ventilator rate could be found from a standard sequence 30, 60, 90, 120 breaths/min which provoked a synchronous interaction, but with increasing postnatal age apnoea became more common (P less than 0.01). We conclude that the preterm infants' spontaneous respiratory efforts are a less important influence on the outcome of mechanical ventilation following recovery from acute RDS. PMID- 1860432 TI - The relationship between maternal serum zinc levels during pregnancy and birthweight. AB - A retrospective follow-up study to ascertain the relationship between the level of serum zinc and its rate of change during gestation and birthweight was conducted in 476 women of lower socioeconomic status. Serum zinc concentrations measured at approximately 16 (early) and 32 weeks (later) in gestation were both found to be significant predictors of birthweight. Even after controlling for gestational age at birth and other determinants of birthweight, for each microgram/dl increase in serum zinc early and later in pregnancy, birthweight increased by 5.8 and 8.6 g, respectively. Furthermore, after adjustment for initial zinc levels both the total change (beta = -7.0, P = 0.0007) and the rate of change (beta = -60.8, P = 0.007) in serum zinc during pregnancy were inversely associated with birthweight, i.e., the larger the fall in serum zinc during pregnancy, the smaller the infant. Low serum zinc level (less than 60 micrograms/dl) late in pregnancy was associated with greater than a five-fold increase in the odds (OR = 5.8, 95% CI = 1.8, 16.4) of giving birth to a low birthweight infant. The results of this study suggest a threshold for maternal serum zinc below which the prevalence of low birthweight increases rapidly. PMID- 1860433 TI - Evaluation of two endotracheal suction regimes in babies ventilated for respiratory distress syndrome. AB - All low birthweight babies ventilated for the respiratory distress syndrome during a period of fourteen months were randomised to receive endotracheal suction 12-hourly or 6-hourly. There were no significant differences in respiratory outcome between the groups. These observations suggest that it is safe to aspirate endotracheal tubes infrequently during the first few days in uncomplicated respiratory distress syndrome. PMID- 1860434 TI - Growth and motor development in fetuses of women with type-1 diabetes. I. Early growth patterns. AB - Early embryonic and fetal growth were followed longitudinally in 23 women with type-1 diabetes to investigate whether there was any evidence of early growth delay and, if so, when it originated and when catch-up growth occurred. Weekly crown-rump length (CRL) measurements were taken between 7 and 14 weeks of gestation; the biparietal diameter (BPD) of the fetal head was measured once every 2-4 weeks from 13 to 30 weeks of gestation. Data were compared to those of a control group and to control data published in the literature. The CRL of the fetuses in the diabetic group was generally shorter than that observed normally. Six out of the 23 (26%) fetuses showed true early growth delay (a size smaller than normal by 6 days or more). Growth delay was present from the first recording onwards and must therefore have occurred before the seventh gestational week. Fetal growth (BPD) was found to be normal at around 20 weeks and there was evidence of accelerated growth of the BPD during the second trimester in fetuses that became macrosomic. Early embryonic growth delay was most profound in the women whose periconceptional quality of glucose control was poor, although the relationship with the HbAlc values was not statistically significant. It is concluded that fetuses of women with type-1 diabetes, as a group, have a significantly different growth pattern than control fetuses throughout the first 30 weeks of pregnancy. PMID- 1860435 TI - Effect of cholecystectomy on the relationship between hydrostatic common bile duct pressure and sphincter of Oddi motility. AB - The sphincter of Oddi (SO) motility before and after an artificial elevation of the common bile duct pressure was studied by means of endoscopic manometry in nine female subjects, seven of whom had undergone previous cholecystectomy. An increase in the hydrostatic common bile duct pressure resulted in total inhibition of the phasic SO contractions in the two patients with gallbladders in situ, as well as in four of the cholecystectomized patients. The results thus indicate that the inhibitory effect of hydrostatic common bile duct pressure on the SO motility previously demonstrated in the cat is also present in man. On the other hand, as the inhibition of the phasic contractions failed to occur in three of the postcholecystectomy patients, the findings also suggest that cholecystectomy may result in altered regulation of SO motility in some patients. This mechanism could then contribute to development of pain in susceptible subjects postcholecystectomy. Finally, the results also showed that pain experienced by some patients upon contrast injection during ERCP bears no relationship to SO motility, but is due to an interindividually variable sensitivity of the bile duct wall to the intraluminal pressure variation. PMID- 1860436 TI - In vitro measurement of the length of the sphincter of Oddi. AB - A study to determine the length of the sphincter of Oddi was performed using 148 autopsy specimens with adjacent structures obtained from adults. The median diameter of the common bile duct was 7 mm (range 4-13 mm). The median intramural length of the sphincter measured at gross examination of 75 specimens was 14 mm (range 7-22 mm); the median length of the common channel between the common bile and pancreatic ducts was 3 mm (range 0-9 mm). Longitudinal histological preparations for microscopic examination were made of 73 specimens. The median extramural length of the sphincter was 5 mm (range 1-11 mm). No associations were found between the length of the sphincter, intramural or extramural, and the diameter of the common bile duct, age, sex, presence of stones in the gallbladder or the postcholecystectomy state, nor was there an association between the intramural and extramural length of the sphincter (p greater than 0.05). PMID- 1860437 TI - Value of endoscopic ultrasonography in the detection of anomalous connections of the pancreatobiliary duct. AB - Endoscopic ultrasonography (EUS) was evaluated in the detection of anomalous connection of the pancreatobiliary duct (ACPBD), which is known to cause cholangitis and has been found to be associated with cholangiocarcinoma. Fourteen patients with ACPBD were examined preoperatively by EUS in addition to ERCP and/or PTC. In all cases, the anomalous connections between the biliary and pancreatic duct were demonstrated to be located outside the proper muscle of the duodenal wall and within the pancreatic parenchyma. EUS classification of ACPBD corresponded well with the findings obtained by retrograde ductal opacification on ERCP and PTC. Biliary malignancy complicating ACPBD was detected correctly by EUS in two patients. In contrast, no connections between biliary and pancreatic ducts were found by EUS in 13 normal controls. It is concluded that EUS is highly sensitive in detecting ductal anomaly in ACPBD. Further studies will show if EUS can replace ERCP in the diagnosis of ACPBD. PMID- 1860438 TI - Analysis of gastric carcinoma growth by endoscopic ultrasonography. AB - Endoscopic ultrasonography (EUS) was performed preoperatively in 82 patients with gastric carcinoma (40 with early and 42 advanced malignancy). Measurements of wall thickness were performed in each case and showed good correlation with histological findings. Wall thickening was found to consist of both tumorous and accompanying ulcerous tissue. Thus, increasing wall thickness, as demonstrated by EUS, may not necessarily mean progressive tumor growth. The EUS features of gastric carcinoma were analyzed and four distinct growth patterns found: predominantly intramural (IM) or intraluminal (IL) growth with preservation (Type 1) or destruction (Type 2) of the submucosal echo-rich layer. All early carcinomas displayed the IL-type growth pattern on EUS (98% IL1-type) and 81% of advanced tumors showed IM-type features. EUS was able to differentiate between early and advanced carcinoma in 98% of cases. The EUS pattern of submucosal destruction (type IM2 or IL2) corresponded to the expanding type tumor according to Ming's histopathological classification. On the other hand, 24 of 26 infiltrative tumors according to Ming were found on EUS to have an intramural growth pattern with preservation of the submucosa (type IM1). It is concluded that EUS is highly sensitive in predicting the tumor growth pattern in gastric carcinoma, providing important additional information to the currently used TNM staging system. Measurements of wall thickness are reliable but differentiation between tumorous growth and peritumorous changes is not possible. PMID- 1860439 TI - Investigation of the effect of duodenoscopy on sphincter of Oddi manometry. AB - To investigate whether endoscopy affects sphincter of Oddi (SO) manometry, three patients who had undergone previous cholecystectomy and had a T-tube in situ for drainage were studied. Manometry was performed using a perfused triple lumen manometry catheter (diameter 1.7 mm), which was advanced into the SO lumen through the T-tube. SO motility, baseline pressure, common bile duct pressure and duodenal pressure were monitored before and during endoscopy while the tip of the endoscope was in the mouth, esophagus (upper third, precardial), stomach and duodenum. Endoscopy and even a moderate insufflation of air necessary to pass the pylorus and inspect the papilla of Vater did not affect the parameters mentioned. Thus, ERCP manometry is a reliable method for evaluation of SO motility which is not affected by endoscopy. Duodenal pressure is a stable parameter and suitable for serving as reference pressure. PMID- 1860440 TI - Bridging of benign choledochal stenoses by endoscopic retrograde implantation of mesh stents. AB - A prospective study of a new stent for bridging choledochal stenoses was performed in seven patients (5 females, 2 males, age range 49-80 years) with benign bile duct stenosis or bilioduodenal fistula in whom conventional bougienage (3 patients) and/or month-long implantation of plastic prostheses (7 patients) failed because of reocclusion. The self-expanding mesh stents (Wallstent) were implanted by duodenoscopy in six patients. In one patient with a B-II stomach, the stent could only be inserted by the percutaneous transhepatic route. All prostheses were inserted endoscopically without complications. At follow-up after an average of eight months prosthesis-related complications were found in only one patient; there was no case of prosthesis occlusion. One patient with a bilioduodenal fistula of unknown origin developed fever and sepsis three days after implantation and subsequently a liver abscess which resolved on repeated drainage and antibiotic therapy. Although definitive interpretation of the results requires a longer follow-up period, on the basis of the present data endoscopic reconstructive splinting of benign choledochal stenosis would appear to be a promising technique. PMID- 1860441 TI - Application of sphincter of Oddi manometry in routine clinical investigations. PMID- 1860442 TI - Endosonography--what are the limits in gastroenterological diagnostics? PMID- 1860443 TI - Endoscopy simulation: a brave new world? PMID- 1860444 TI - Experimental evidence of beneficial effects of ductal decompression in chronic pancreatitis. PMID- 1860445 TI - Chronic pancreatitis: selection of patients for endoscopic therapy. PMID- 1860446 TI - Fragmentation of pancreatic stones by extracorporeal shock wave lithotripsy. PMID- 1860447 TI - Laser fragmentation of pancreatic stones. PMID- 1860448 TI - Stenting in severe chronic pancreatitis: results of medium-term follow-up in seventy-six patients. AB - Between January 1985 and September 1989, 75 patients presenting with severe chronic pancreatitis with distal stricture and upstream dilatation underwent stenting of the main pancreatic duct (MPD) through the major papilla (n = 54) or minor papilla (n = 21) in order to drain the predominant duct through a 10 F plastic prosthesis. All patients had undergone biliary and pancreatic sphincterotomy with a few cases of complications, and the majority (84%) also ESWL in the period from October 1987 onwards without complications. Relief of pain (94%) occurred parallel to a decrease in the MPD diameter. In a mean follow up period of 37 months improvement of the nutrition status and relief of pain was seen. Clogging of these large plastic stents was treated by replacement or by another endoscopic or surgical procedure. Complications were treated endoscopically. Further measures necessary due to failure of stenting consisted of laterolateral pancreatico-jejunostomy in 15% of patients and placement of self expanding 18 F metal mesh stents in 29%. There was no mortality due to surgery. It is concluded that stenting of distal strictures in the MPD can lead to rapid resolution of pancreatic pain due to ductal hypertension and is the best means for determining the cause of pain, providing an alternative to surgery. Significant improvement of a stricture by prolonged stenting is however unusual, and such patients treated endoscopically require close follow-up with stent replacement approximately once a year. PMID- 1860449 TI - Endoscopic management of pancreatic disorders: potential risks of pancreatic prostheses. PMID- 1860450 TI - A critical appraisal of interventional therapy in chronic pancreatitis. PMID- 1860451 TI - Biology of airway basal cells. PMID- 1860452 TI - Biochemistry and pharmacology of mucin-like glycoproteins produced by cultured airway epithelial cells. PMID- 1860453 TI - Suppression and recovery of the alveolar macrophage phagocytic system during continuous exposure to 0.5 ppm ozone. AB - Short-term exposures to ozone (O3) are known to impair pulmonary antibacterial defenses and alveolar macrophage (AM) phagocytosis in a dose-related manner. To determine the effect of prolonged O3 exposure, Swiss mice were exposed continuously to 0.5 ppm O3. At 1, 3, 7, and 14 days, intrapulmonary killing was assessed by inhalation challenge with Staphylococcus aureus or Proteus mirabilis and by comparing the number of viable bacteria remaining in the lungs at 4 h between O3-exposed and control animals. To evaluate the effects of O3 on the functional capacity of the AMs, Fc-receptor mediated phagocytosis was assessed. Ozone exposure impaired the intrapulmonary killing of S. aureus at 1 and 3 days; however, with prolonged exposure, the bactericidal capacity of the lungs returned to normal. This trend of an initial suppression followed by recovery was reflected in the phagocytic capacity of the AMs. In contrast to S. aureus, when P. mirabilis was used as the challenge organism, O3 exposure had no suppressive effect on pulmonary bactericidal activity, which correlated with an increase in the phagocytic cell population in the lungs. Morphologic examination of the lavaged macrophages showed that after 1 day of O3 exposure, the AMs were more foamy, and contained significantly more vacuoles. There was also a significant increase in binucleated cells at 3 days. These studies demonstrate that continuous exposure to O3 modulates AM-dependent lung defenses and points to the importance of the challenge organism and exposure protocol in establishing the adverse effect of O3. PMID- 1860455 TI - Epithelial injury, inflammation, and repair in the hamster lung following intratracheal instillation of enzyme-generated oxidants. AB - Oxidant-induced inflammatory and morphologic changes evoked by intratracheally instilled glucose, active glucose oxidase, and lactoperoxidase in hamsters are described. Similar solutions containing heat-denatured (DE) glucose oxidase served as a control treatment. During the 7-week post-treatment period, animals were sacrificed and lavaged, and their lungs were preserved for later study. Although a neutrophil-rich alveolitis was observed initially in both groups, the leukocytic influx and mild morphologic changes in DE-treated animals resolved within 7 days. In contrast, glucose oxidase mixtures caused necrotic alveolar epithelium, fibrin-like exudate, and significantly higher neutrophil and protein levels in bronchoalveolar lavage fluid (BALF) after 1 day. At 4 days, type II cell hyperplasia was extensive and BALF levels of all inflammatory cell types were significantly greater than BALF counts in DE animals. By 7 days, BALF macrophage and lymphocyte levels remained significantly elevated, and epithelial hyperplasia coincided with marked increases in lung hydroxyproline and interstitial cells. BALF parameters suggested that inflammation induced by glucose oxidase resolved within 15 days, yet total hydroxyproline levels remained elevated at 15 days and epithelial lesions were still detectable at 29 days. Oxidant-induced inflammation and epithelial injury were transient and preceded moderate collagen deposition. PMID- 1860454 TI - Identification, isolation, and partial characterization of a 7.5-kDa surfactant associated protein. AB - Human surfactant was analyzed for proteins associated with the lipids. Surfactant was isolated from lung lavage by the salt gradient centrifugation method, and the soluble proteins binding to the lipids were recovered by extraction with a low pH buffer. Antiserum to this preparation reacted with surfactant apoprotein A and a 7.5-kDa protein. The 7.5-kDa protein was isolated from reduced and alkylated lung lavage pellet by chromatography. The N-terminal amino acid sequence of the protein indicates that it is a novel protein. PMID- 1860456 TI - Effect of cumulative ozone exposure on ozone-induced nasal epithelial hyperplasia and secretory metaplasia in rats. AB - Repeated exposure of rats to O3 induces proliferative and secretory metaplastic changes within nasal airway epithelia that may protect against subsequent exposures. Our study assessed the effect of different cumulative exposure times on O3-induced nasal epithelial hyperplasia and secretory metaplasia. Rats were exposed 6 h/day to air or to 0.8 ppm O3 and were sacrificed 18 h after the end of their last exposure. The rats were exposed to either air or 0.8 ppm O3 for 3 or 7 days, or to 0.8 ppm O3 for 3 days followed by a 4-day exposure to air. The effects of the exposures were determined by quantitating the hyperplastic (epithelial nuclei/mm basal lamina) and secretory metaplastic changes (volume densities of acidic and neutral mucosubstances) within the nasal nonciliated cuboidal epithelium (NNCE). There were no significant changes in NNCE cell numeric density, or in the volume density of intraepithelial mucus, compared to air-exposed control rats, in rats exposed to O3 for 3 days and sacrificed 18 h later. Compared to control rats, there was significant epithelial hyperplasia and secretory metaplasia within the NNCE of rats exposed to O3 either for 7 days or for 3 days followed by 4 days of exposure to air. There were no significant differences in NNCE cell hyperplasia or secretory metaplasia between these two experimental groups. Three 6 h/day exposures to 0.8 ppm O3 triggered hyperplastic and metaplastic changes within rat NNCE that were indistinguishable from those produced by seven 6 h/day exposures to the same concentration of O3. The data suggest that O3 is capable of rapidly inducing hyperplastic and metaplastic responses within rat NNCE, and that once initiated, development of the phenotypic changes within the epithelium does not require further O3 exposure. PMID- 1860457 TI - Damage and repair of mouse bronchial epithelium following acute inhalation of trichloroethylene. AB - The time-course of damage and repair in the bronchial epithelium of the mouse was studied morphometrically after a single inhalation of trichloroethylene (TCE). Mice were exposed for 30 min to 500, 1000, 2000, 3500, or 7000 ppm of TCE under controlled conditions and sacrificed after 2 and 24 h, and 2, 5, and 7 days. At all TCE concentrations, the damage consisted of dilation of endoplasmic reticulum and was selective for nonciliated cells throughout the bronchial tree. Damage was quantitatively evaluated by counting the percentage of vacuolated cells. Injury was maximal 24 h after exposure and was significantly (p less than 0.05) higher in bronchi with a diameter smaller than 0.4 mm (67.0% +/- 8.5%) in comparison with larger bronchi (34.0% +/- 13.2%). Cell turnover was studied by autoradiography after [3H]thymidine injection. Following TCE inhalation, the percentage of [3H]thymidine labeled cells, which in the controls was virtually zero, increased to a maximum of 13.5% +/- 6.8% (average at all doses) 48 h after treatment and then rapidly decreased to baseline values at 7 days (0.2% +/- 0.1%). Repair of some cells occurred after 24 h, and at 48 h the percentage of vacuolated cells decreased and became significantly related (p less than 0.01) to the administered TCE dose (2.4% +/- 1.4% and 21.2% +/- 6.0% average in the 500 and 7000 ppm groups, respectively). Repair of bronchial epithelium took place by both recovery of less damaged cells and proliferation of residual nonciliated cells, leading to restoration of the normal ratio between ciliated and nonciliated cells. PMID- 1860458 TI - Hydroperoxide-induced broncho- and vasoconstriction in the isolated rat lung. AB - The effects of different hydroperoxides on lung mechanics and perfusate flow rate and their mechanisms of action were studied in isolated perfused rat lungs. The administration of hydrogen peroxide, t-butyl hydroperoxide, cumene hydroperoxide, linoleic acid hydroperoxide, and linoleic acid ethylester hydroperoxide (0.1-2 mM) to the perfusate caused a marked decrease in lung compliance, conductance, and perfusate flow rate, with constriction strength of t-butyl hydroperoxide greater than hydrogen peroxide greater than cumene hydroperoxide greater than linoleic acid ethylester hydroperoxide greater than linoleic acid hydroperoxide. Although the hydroperoxides probably had to enter lung cells to exert their effects, no relationship was found between constriction strength and amount of hydroperoxide taken up by the lung. Reduced sensitivity was apparent after repeated dosing, depending on the length of time between dosing. The addition of the iron chelator Desferal (1 mM) had no effect on the hydroperoxide-induced broncho- and vasoconstriction, although free iron was reduced by 50% in the lungs. The administration of the antioxidants diphenyl-p-phenylenediamine (50 microM) or butylated hydroxyanisole (200 microM) to the perfusate 20 min prior to the hydroperoxide attenuated the hydroperoxide-induced effects as well as arachidonic acid-induced broncho- and vasoconstriction. Our findings have shown that hydroperoxides that can enter the lung cells will also induce both vaso- and bronchoconstriction in the isolated perfused rat lung. PMID- 1860459 TI - Effect of corticosteroid therapy on the acute injury and recovery stage of oleic acid induced lung injury in the rat. AB - In the rat model of lung injury induced by oleic acid (OA), we studied the effect of corticosteroid therapy on pulmonary inflammation and compliance at acute (1 day post OA) and recovery (3 and 7 days post OA) stages. Methylprednisolone (MP) and dexamethasone (DM) were examined for therapeutic benefit in this model. Histologic examination, lung compliance, and analysis of bronchoalveolar lavage (BAL) fluid were used to assess lung injury. Our results demonstrated that, at 1 day post OA, both steroids effectively reduced pulmonary inflammation and restored lung compliance when compared to animals that received only OA. In comparison to DM, MP was more effective in inhibiting the pulmonary inflammation induced by OA, but was less effective in restoring lung compliance. However, at 3 and 7 days post OA, cell and/or protein levels in BAL fluid from both MP- and DM treated OA animals were significantly higher than levels observed in animals that received only OA. Lung compliance returned to normal by 3 days in animals that received only OA. This effect, however, was blocked in OA animals that were treated with either steroid, MP, or DM. Our data suggest that steroid therapy can be beneficial in the acute stage of OA-induced lung injury, but appears to be detrimental during the early recovery stage, perhaps by inhibiting the repair process. PMID- 1860460 TI - A comparison of hand and foot movement times. AB - Three experiments are reported in which a comparison is made between the times for movement of the hand and the foot. Both ballistic and visually-controlled movements were studied. It was found that execution time for foot movements is generally about twice as long as that for the equivalent arm movement. The times for foot movements were described well by the Welford, Norris and Shock modification of Fitts' Law for visually-controlled movements and, for ballistic movements, by the square-root-of-amplitude equation found by Hoffmann for arm movements. PMID- 1860461 TI - A biomechanical and ergonomic evaluation of patient transferring tasks: wheelchair to shower chair and shower chair to wheelchair. AB - A laboratory study was conducted to evaluate five different manual techniques (two-person manual lifting; rocking and pulling the patient using a gait belt with two persons; walking belt with one and two persons) and three different mechanical hoists (Hoyer lift, Trans-Aid and Ambulift) for transferring patients from wheelchair to shower chair and shower chair to wheelchair. Six female nursing students with prior patient transfer experience served both as nurses and as passive patients. Static biomechanical evaluation showed that the mean trunk flexion moments, erector spinae muscle forces and compressive and shear forces at the L5S1 disc for the four pulling methods ranged from 92 to 125 Nm, 1845 to 2507 N, 1973 to 2641 N and 442 to 580 N, respectively, as compared to about 213 Nm, 4260 N, 5050 N and 926 N for two-person manual lifting. Perceived stress ratings for the shoulder, upper back, lower back and whole body were significantly lower for pulling methods than those for lifting the patient (p less than or equal to 0.01). Patients found pulling techniques, except the gait belt, to be more comfortable and secure than the lifting method (p less than or equal to 0.01). However, most of the nurses believed that Medesign and the one-person walking belt would not work on those patients who cannot bear weight and those who are heavy, contracted or combative. A two-person walking belt was the most preferred method. Two out of three hoists (Hoyer lift and Trans-Aid) were perceived by the nurses to be more stressful than one- and two-person walking belts. The patients found these two hoists to be more uncomfortable and less secure than with three of the five manual methods (one- and two-person walking belts and Medesign). Pulling techniques and hoists took significantly longer amounts of time to make the transfer than manually lifting the patient (p less than or equal to 0.01). The two-person walking belt, using a gentle rocking motion to utilize momentum and a pulling technique, and Ambulift are recommended for transferring patients from wheelchair to shower chair and shower chair to wheelchair. PMID- 1860462 TI - Inertial effects from single body segments in dynamic analysis of lifting. AB - Biomechanical calculations of loads on the locomotor system in lifting tasks are often based on static models. Several investigators have shown, though, that in a dynamic act like lifting, inertial effects are not generally negligible. A complete dynamic analysis includes the calculation of linear and angular accelerations of body segments and is rather complicated to carry out. So it was of interest to find out whether the contribution of single body segments to the dynamic effects of the whole body might be negligible. Ten male subjects lifted a 12.8 kg box using two different techniques and two speeds. Ground reactions and body segment movements were recorded and reaction forces and net moments at different joints were calculated with static, dynamic and 'semidynamic' methods. The latter method incorporated the ground reaction forces as measured from a force plate but was otherwise equal to the static method. The results from semidynamic analyses agreed well with those from complete dynamic analyses for the ankle, knee, hip, and L5/S1 joints. For example, the semidynamically calculated peak moments at L5/S1 differed on average less than 3% from the dynamically calculated values. The contributions of the lower extremities and the pelvis to the dynamic effects of the whole body seemed to be quite small. The less complicated semidynamic method offers a good alternative to a fully dynamic analysis for estimations of peak moments in the lower back, at least for the studied lifting techniques. PMID- 1860463 TI - Effects of thermal environment and chemical protective clothing on work tolerance, physiological responses, and subjective ratings. AB - This study examined the physiological and subjective responses of nine healthy men who performed work while wearing two types of protective ensembles in each of three thermal environments. The subjects, all experienced with the use of protective ensembles, each performed low intensity treadmill exercise (23% of VO2 max while not wearing a Self-Contained Breathing Apparatus [SCBA] or protective clothing) under six experimental conditions: two ensembles (SCBA--light work clothing and SCBA; and CHEM--a two-piece chemical protective ensemble with SCBA) during exposure to 'cool' (10.6 degrees C/water vapour pressure [Pw] 0.76 kPa), 'neutral' (22.6 degrees C/Pw 1.52 kPa), and 'hot' (34 degrees C/Pw 2.90 kPa) environments. Each test was intended to continue for 120 min; however the duration and number of work/rest periods within the testing session varied according to the specific responses of each individual. At the completion of each test seven subjective responses were recorded. Physiological data, collected every minute during each test, included heart rate, and skin and rectal temperature. The total worktime was significantly shorter in the hot environment while wearing the CHEM ensemble (53.4 min) compared to all the other conditions (103-105 min). The mean maximum physiological values also indicated significant differences due to thermal environment and/or ensemble. Work performance did not appear to be limited in a cold environment with either ensemble tested. The physiological responses to working in the CHEM/neutral condition were very similar to those occurring in a hot environment wearing the SCBA ensemble. The subjective responses also indicated significant differences due to thermal environment and ensemble, with subjects perceiving the CHEM ensemble as less favourable than the SCBA ensemble. The results suggested that, even at a low work intensity, individuals wearing chemical protective clothing in the heat will require progressively shorter work periods, and more frequent and longer rest periods. PMID- 1860464 TI - Psychophysical acceptability and perception of load heaviness by females. AB - The objective of the study was to evaluate subjective perceptions of load heaviness, and relate these perceptions to the maximal acceptable weights of lift. Ten female college students experienced in manual lifting participated in the study. In the first experiment, subjects were asked to select one of the seven linguistic values of load heaviness (very light, light, less-than-medium, medium, more-than-medium, heavy, and very heavy), which would best describe the lifted loads. Seven boxes, ranging in weight between 2.3 kg and 22.7 kg, were used for that purpose. In the second experiment, subjects were asked to fill empty boxes to the level they felt would best reflect a given load heaviness category. In the third experiment, the psychophysical methodology was used to determine the maximal acceptable weight of lift for an 8-hour day. The results showed that 50% of the subjects considered a 20.4 kg box (45 lbs) as very heavy, while another 50% believed that such a load was heavy. The average load selected as maximal acceptable weight of lift (MAWL) for an 8-hour day was 16.4 kg (standard deviation (SD) = 5.3 kg). When asked to determine the weights that would best describe a given category of load heaviness, the subjects selected 22.5 kg (SD = 3.7 kg) and 18.4 kg (SD = 2.7 kg) for very heavy and heavy categories, respectively. Further analysis revealed that only 30% of the subjects selected MAWL values that were larger than the pre-weighted boxes independently judged by them as very heavy or heavy categories. Also, 10% and 30% of the subjects selected MAWL values that were larger than the weights chosen during the self-classification procedure as representative of heavy or very heavy categories of load heaviness, respectively. It was shown that the loads selected as the maximum acceptable weights for an 8 h shift were independently judged by the female subjects as being in the more-than-moderate or heavy weight categories. Comparison of the results for females and males led to a conclusion that female subjects were more realistic, with respect to subjective perception of load heaviness, in selecting the MAWL values than were male subjects. PMID- 1860465 TI - Three-dimensional face shape analysis of French adults, and its application to the design of protective equipment. AB - The study's aim was to identify female and male face shape variability in order to establish typical profiles for the design of masks. A specific data acquisition photogrammetric station was used for this purpose. A preliminary survey using anthropometric techniques was conducted on 301 females and 208 males, randomly selected from the French military population, in order to constitute two samples of 30 males and 30 females for the stereometric survey. For each subject, the stereorestitution of face photos was made on three sets of data: (1) 37 anatomical landmarks previously identified by a black point marked on the face; (2) 7 anatomical arcs, also drawn with a black pencil; and (3) 1500 2000 points distributed on horizontal cross-sections at different vertical levels. The analysis only concerned the global face shape, and excluded the central area (eyes, nose and mouth). A common origin and reference axis system was defined. All the three-dimensional (3D) produced data was processed using computer-aided design software, after some adaptations. Subjects were selected iteratively for five levels of cross-section and three anatomical arcs so as to characterize least variation amplitudes, subject by subject. Five groups were identified. All cross-sections were verified to check the validity of the preceding step. By this method, each group was defined by a mean profile form and by the amplitude of this form for each point of the profile. Males and females were present in each group, and for each group, a greater variability was noted at the lower part of the face. This variability can be explained as the result of morphological and functional phenomena. These results can be applied to the design of new protective equipment for the fore-face indeed they were used for the design of a new mask for the French military. PMID- 1860466 TI - Short-term haemodynamic evolution and late follow-up of post-infarct patients with left ventricular dysfunction undergoing a physical training programme. AB - The aims of this study were to investigate the short-term haemodynamic changes occurring in post-infarct patients with left ventricular dysfunction undergoing a physical training programme and the prognostic implications of such changes. Ninety-five male patients with no evidence of congestive heart failure, consecutively admitted for exercise testing with haemodynamic monitoring in the supine position, in whom exercise pulmonary artery diastolic pressure (PAdP) exceeded 20 mmHg were enrolled in an in-hospital one-month physical training programme. After training all patients' exercise capacity increased by 24% (P less than 0.001) with no change of PAdP. At matched work load, heart rate decreased (126 +/- 21 vs 120 +/- 19 bt min-1, P less than 0.05) as did PAdP (27 +/- 5 vs 25 +/- 6 mmHg, P less than 0.05) and A-VO2 difference increased (9.5 +/- 1.7 vs 10 +/- 1.6 ml%, P less than 0.01). Similar results were observed in a subset of patients with exercise PAdP greater than 30 mmHg (30 patients). In 11 patients with inadequate cardiac output neither heart rate nor PAdP decreased after training and a disproportionate increase in blood pressure was noted. Clinical follow-up ranged from 1 to 8 years (62 +/- 32 months). Seven deaths, 12 reinfarctions and 14 coronary artery bypass graftings occurred. The modifications, after training in work capacity, heart rate and PAdP, were not predictive of events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860467 TI - Closing click of St Jude Medical and Duromedics Edwards bileaflet valves: complaints created by valve noise and their relation to sound pressure and hearing level. AB - The metallic clicking sound created by mechanical heart valve prostheses frequently bothers patients. To test whether sounds generated by different bileaflet valves correlate to complaints related to the prosthetic clicking 73 patients were investigated after valve replacement with Duromedics Edwards (DE) (n = 38) and St Jude Medical (SJM) (n = 35) valves. The patients were asked about their complaints, sound pressure levels were recorded and audiometry was performed. Sixty-five percent of patients could hear their valve, 18% had sleeping disturbances, 5% felt bothered during daytime and 12% would prefer a less noisy valve. In symptomatic patients, sound pressure levels were higher than in asymptomatic patients (valve audible 45 +/- 8 db(A) vs not audible 39.9 +/- 10 db(A) at 10 cm; P = 0.016). These differences were most apparent in the high frequency bands, corresponding to the metallic click. Symptomatic patients had better hearing and were younger than patients without complaints. Fifty-one percent could hear their valve by conduction through the body, after eliminating air conduction by the use of headsets. The DE prostheses were louder than the SJM valves in general (47.4 +/- 7 vs 39.8 +/- 5 db (A) at 10 cm; P = 0.001) and in each valve position. Patients with DE prostheses had significantly more complaints. The intensity of the closing click of mechanical valves correlates to the complaints caused by prosthetic clicking and thus sound emission should be considered when a mechanical heart valve prosthesis is selected. PMID- 1860468 TI - Aortic valve replacement with the Lillehei-Kaster prosthesis in 262 patients: an assessment after 9 to 17 years. AB - A 9 to 17-year follow-up after aortic valve replacement with the Lillehei-Kaster prosthesis was carried out in 262 patients with a mean age of 53 years. All patients were traced. The operative mortality was 7.3%. The observed survival of the total series after 5, 10 and 15 years amounted to 75%, 61%, and 49% respectively. The majority of survivors showed improvement of functional capacity and decrease of heart volume. Freedom from valve-related death, thromboembolism and valve-related morbidity and mortality after 15 years amounted to 94%, 85% and 75% respectively. Only two instances of valve thrombosis were seen, and fracture of the prosthesis was never encountered. These results compare favourably with those obtained with the Starr-Edwards and the Bjork-Shiley prostheses. Analysis of the relative survival rates, i.e. the observed survival rates as ratios of those of the general population, indicates that the 10-year survival of patients with aortic stenosis is close to normal, whereas the survival rates of patients with aortic incompetence and with combined aortic stenosis and incompetence are significantly lower. It is suggested that earlier operation should be considered in patients with aortic incompetence and with combined stenosis and incompetence in order to lower the late mortality rate. PMID- 1860469 TI - Release of creatine kinase-MB and cardiac specific troponin-I following percutaneous transluminal coronary angioplasty. AB - Up to 20% of patients undergoing successful coronary angioplasty have been shown to have a mild elevation of creatine kinase-MB (CK-MB). The purpose of this study was to investigate the relationship between clinical and angioplasty procedural variables and circulating markers for cardiac injury. We measured both CK-MB and totally cardiac-specific troponin inhibitory protein (Tn-I) in 22 patients immediately before and at an average time of 10 h 36 min following successful angioplasty. Of these patients 16 had stable angina, six had unstable angina and none had recent myocardial infarction. Four patients had minor complications associated with the procedure (prolonged chest pain, limited coronary artery dissection) but none of these patients had increases in either CK-MB or Tn-I. In two patients there was a mild increase in enzyme-activity assayed CK-MB but none of the 22 patients had significant elevation of mass-assayed CK-MB or cardiac specific Tn-I. This study supports the view that no significant myocardial damage occurs as a result of successful coronary angioplasty irrespective of the stability of the coronary artery disease. This study confirms the known discrepancies between results obtained by immunoassay and immunoinhibition enzyme assay, due to the false-positive results which can be yielded by the latter technique. PMID- 1860470 TI - Triglycerides, a major coronary risk factor in elderly men. A study of men born in 1913. AB - We examined two 'cohorts' of elderly men, 60 and 67 years old. The two 'cohorts' overlapped to a large extent in terms of numbers but not in the follow-up periods. The mean have been followed-up for 7 and 8 years respectively. Among the 748 60-year-old men without prior myocardial infarction the 7-year incidence of coronary heart disease was 8%. The incidence was related to blood pressure, smoking habits and serum triglycerides (but not serum cholesterol) both in univariate and multivariate analyses. The incidence of coronary heart disease increased 5-fold from the lowest to the highest quintile of triglycerides. Among the 595 67-year-old men without prior myocardial infarction the 8-year incidence of coronary heart disease was 11%. Both serum cholesterol and triglycerides were significant risk factors in univariate analyses but only triglycerides in multivariate analyses. The incidence of coronary heart disease increased almost three-fold from the lowest to the highest quintile of triglycerides. Increased serum triglycerides is a major coronary risk factor in elderly men. PMID- 1860471 TI - Acute haemodynamic effects of carvedilol in essential hypertension at rest and during exercise. AB - The acute haemodynamic effect of carvedilol, a new non-selective beta-receptor blocker with vasodilating effect, was examined at rest supine and sitting and during 100 W bicycle exercise in 18 patients (mean age 44 years) with essential hypertension. Intra-arterial blood pressure and heart rate were recorded continuously. Cardiac output was measured by dye dilution (Cardiogreen). Two h after the first oral dose (12.5-25 mg) of carvedilol, blood pressure was reduced in all patients sitting at rest, from 176/110 to 153/101 mmHg (P less than 0.001), associated with a reduction in cardiac index (16%; P less than 0.001) while total peripheral resistance remained unchanged or was slightly reduced. When sitting up after 2 h supine rest two patients had hypotensive reactions (excessive blood pressure drop; cold, pale, sweating skin) which disappeared after lying down with elevation of the legs and light physical exercise. The fall in cardiac index was due to reduction both in heart rate (8%, P less than 0.001) and stroke index (9%; P less than 0.01). During exercise the reduction in cardiac output was less (6%; P less than 0.05) while a clear reduction (6%; P less than 0.01) was seen in total peripheral resistance. This acute haemodynamic response is different from that seen immediately after conventional beta-blockers when total peripheral resistance always increases. PMID- 1860472 TI - Right coronary artery originating from distal left circumflex: an unusual feature of single coronary artery. AB - This report describes a patient with a single coronary artery system, in whom the right coronary artery originated from the distal left circumflex. A significant stenosis was present just at the take-off of the aberrant right coronary artery. No other associated cardiac anomaly could be demonstrated; the patient was referred for elective bypass surgery. PMID- 1860473 TI - AIDS risk among runaways. PMID- 1860474 TI - HIV testing at public clinics. PMID- 1860475 TI - Adult sexual behavior in 1989: number of partners, frequency of intercourse and risk of AIDS. AB - Questions on sexual behavior that were added to the National Opinion Research Center's 1988 and 1989 General Social Surveys reveal that 97 percent of adult Americans have had intercourse since age 18. Respondents report having an average of about 1.2 sexual partners during the year preceding the survey and nearly 7.2 partners since age 18; men claimed to have had considerably more partners than did women. About one-fifth of adult Americans had no partners during the previous year. Moreover, over a year's time, only 1.5 percent of married people reported having had a sexual partner other than their spouse. On average, adults report engaging in intercourse 57 times per year. About two percent of sexually active adults reported being exclusively homosexual or bisexual during the year preceding the survey, and 5-6 percent have been exclusively homosexual or bisexual since age 18. Seven percent of adults are at relatively high current risk of contracting AIDS--three percent because they have had multiple partners, three percent because they have had unfamiliar partners and one percent because of their sexual orientation. However, 33 percent have engaged in relatively risky behavior at some time since age 18. PMID- 1860477 TI - Substance use and prenatal care during pregnancy among young women. AB - Data on a cohort of young mothers from the National Longitudinal Survey of Youth were examined for use of alcohol, cigarettes and marijuana during pregnancies leading to first births. A substantial proportion of women (45 percent) were found to have used at least one of these substances. White women were more likely to use a substance during pregnancy than were Hispanic or black women; women with the prospective father present in the household were less likely than other women to use a substance. Compared with well-educated and older women, less-educated and younger women were more likely to smoke cigarettes or marijuana during pregnancy, but were less likely to drink alcohol. Only about 13 percent of women used more than one substance. Nineteen percent of the women received no prenatal care in the first trimester of pregnancy. Less-educated and younger women were least likely to receive early prenatal care. Multivariate analysis found no association between neglect of prenatal care and substance use. Rather, the analysis revealed that the two behaviors shared likely antecedents, such as whether the prospective father was in the home prior to the pregnancy. PMID- 1860476 TI - Contraceptive use at first premarital intercourse: United States, 1965-1988. AB - The proportion of U.S. women who used a contraceptive method at their first premarital intercourse rose from 47 percent in 1975-1979 to 65 percent in 1983 1988. Overall, and among non-Hispanic white women, this change resulted entirely from an increase in the use of condoms by their partners. The proportion of whites who used a condom at first premarital intercourse, for example, increased from 24 percent to 45 percent. Among blacks, condom use at first intercourse increased from 24 percent to 32 percent during that period, and pill use rose from 15 percent to 23 percent. Among all women, the method most often used at first intercourse during every period in the study was the condom, followed by the pill and withdrawal. The proportion of women using a method at first premarital intercourse varies strikingly according to individual characteristics. Among the various demographic subgroups, the proportion who use a method varies from 32 percent of Hispanic women to 68 percent of Jewish women. Whites are more likely to use a method than are blacks, and fundamentalist Prostestants are less likely to use a method than are other Protestants or Catholics. The proportion using a method is higher among women whose mothers completed high school than among those whose mothers did not. In addition, the proportion rises with age at first intercourse. Multiple logistic regression showed that the independent effects of Hispanic origin, Jewish or fundamentalist Protestant religious affiliation and the education of a woman's mother are large and significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860478 TI - Medicaid and pregnancy: issues in expanding eligibility. AB - Recent federal and state policy has expanded Medicaid eligibility to provide health insurance coverage for pregnant women with family incomes below 133 percent of the federal poverty level. It has yet to be determined how such expanded coverage will affect enrollment in Medicaid or use of prenatal care. Using 1983 data from three states with widely divergent Medicaid programs- including one that already had most of the expanded eligibility options available today--this study found that about 40-60 percent of women who were covered by Medicaid at the time of their deliveries had not been enrolled in the program when they became pregnant. In addition, a large number of women did not receive Medicaid-covered prenatal care early in pregnancy, even though they were enrolled at that time. Almost all women in the study group visited more than one ambulatory care provider at some time during the nine months before birth and one year following birth; 29-51 percent visited more than one hospital outpatient department. PMID- 1860480 TI - How well do women comply with oral contraceptive regimens? PMID- 1860479 TI - Evaluating adolescent pregnancy programs: rethinking our priorities. PMID- 1860481 TI - A followup study of manic-depressive and schizoaffective psychoses after systemic family therapy. AB - The authors report the results of a followup study of manic-depressive and schizoaffective psychoses after systemic family therapy. They describe the development of inpatient relapse rates, familial interactional patterns, and prescriptions of medication in a sample of 30 cases treated with family therapy and followed up after a mean interval of 3 years. Finally, they assess the effectiveness of systemic family therapy with manic-depressive and schizoaffective psychoses. PMID- 1860482 TI - A developmental view of therapeutic bonding in the family: treatment of the disconnected family. AB - Data from an ongoing research study have been used to identify a subgroup of families of severely ill, young adults who present formidable treatment challenges to the family therapist. The disconnected family is characterized by disturbances in attachment between one or both parents and the patient. In many cases, disturbances in attachment and caretaking in the family of origin are reported for the parents in these families. Disconnected families that also have intense emotional styles of relating are particularly difficult to treat. A treatment model that focuses on intergenerational attachment issues is described. PMID- 1860483 TI - Adolescent adjustment to parental divorce: an investigation from the perspective of basic dimensions of structural family therapy theory. AB - This study, conducted within the framework of concepts of structural family therapy, examined the relationship of four family-based, clinical dimensions to the adjustment of 45 adolescents during the first 18 months of parental separation. There were two samples of mother-custody families: an Aided group that applied for treatment, and an Unaided group of paid volunteers. The inclusion of this variable addressed a major methodological deficit of previous studies. There was a significant association between perceived postseparation family structure and adolescent adjustment, demonstrating that individual adolescent adjustment is contingent on structural features of the contemporary postseparation family. Further, Aided families were perceived as more chaotic, disengaged, and enmeshed than Unaided families, while Aided adolescents were characterized by more behavior problems than Unaided adolescents. This suggests that divorce, as an unscheduled transition, might be within the realm of adaptation for many families and adolescents and is not necessarily "disastrous." PMID- 1860484 TI - The family's conception of accountability and competence: a new approach to the conceptualization and assessment of family stress. AB - Clinicians and researchers have a strong interest in understanding how families respond to stress. Often, they begin their analyses by attempts to estimate the seriousness or magnitude of the stressful events impinging on the families they observe. Until now, they have relied on two strategies. First, they attempt to develop objective or external indicators of the magnitude of the stress of the events. The problem here is that the family's own perceptions and experiences are not properly weighted. The second strategy depends heavily or exclusively on the family's perceptions of the events. However, these perceptions are often a product of the family's efforts to cope with the stress since the organization and perception of meaning in events is a fundamental part of family coping. Thus, this approach cannot disentangle the stress inherent in the events from the family's efforts to cope with it. This article explores a third alternative. The social community in which the family lives often provides a coherent frame of meanings for most events. It not only defines the magnitude of the event but it also defines how accountable the family is for producing the event in the first place. A method for assessing these community frameworks is presented. Initial results suggest that there is not only a coherent community framework attributing magnitude and family accountability to a large number of stressful events impinging the family but, also, that these community attributions are embedded in a community concept of family development. PMID- 1860485 TI - Lie to me no more: believable stories and marital affairs. AB - This case study illustrates the dilemmas of systemic practice when the presenting problem is relational infidelity (marital affairs). After several months of treatment with a structural therapist, the couple and therapist were at an impasse because of arguments over the husband's alleged sexual encounter 3 years previously. The introduction of a consultant and a story-based therapy allowed the couple to reconcile their marital difficulties. The article ends with a discussion of the implications of systemic paradigms and personal morality. PMID- 1860486 TI - Priority setting in family change and clinical practice: the Family FIRO Model. AB - We update a theoretical framework for understanding priority setting for the management of family change, with special emphasis on developmental change. We propose that three core dimensions of family interaction--inclusion, control, and intimacy--constitute an optimal priority sequence for managing major family change stemming from life-cycle transitions and other stressful experiences. In the next section of the article, we compare the Family FIRO Model and other models of family change. Finally, we suggest that therapists can benefit from an explicit, clinical decision-making model for setting priorities in treatment: issues of inclusion take precedence over issues of control, which in turn take precedence over issues of intimacy. PMID- 1860487 TI - The BRIEFER project: using expert systems as theory construction tools. AB - This article describes the development of BRIEFER I and BRIEFER II, expert systems that advise the therapist on selecting, designing, and developing an intervention at the end of the first therapy session. The process of developing expert systems has aided us in describing what brief therapists do, in modeling the intervention design process, and in training brief therapists. PMID- 1860488 TI - Family conversation: description and interpretation. AB - This research focused on the analysis of a small segment (1 minute and 8 seconds) of conversation that occurred during a family therapy session. The participants were a mother, daughter, son, and the therapist. Through repeated listening and transcribing, a detailed transcript of the segment was first constructed. The conversational features within the transcript included the interruptions, pauses, overlaps, inflections, and turn shapes as structured by the participants. A sequential analysis of the conversation was rendered by describing the occurrence of the conversational features as well as interpreting the meanings of those features. The potential utility of conversation analysis to developing family theory and improving family therapy is also examined, as well as the limitations of the approach. PMID- 1860490 TI - [A comparative study of the nootropic properties of piracetam and oxiracetam]. AB - The behavioral activities of piracetam and oxiracetam were studied during the learning tests (active avoidance, passive avoidance, T-maize). The levels of the orientation reaction and emotionality of the animals were determined by the "open field" method. To achieve similar effects, injections of 10 mg/kg of oxiracetam and 100 mg/kg of piracetam intraperitoneally were required. Both nootropics facilitated the learning of the animals but failed to change their behavior in the open field. Piracetam was more effective in the active avoidance test and oxiracetam in the T-maize test. The data indicate some differences in the activities of piracetam and oxiracetam. PMID- 1860489 TI - [The influence of the Soviet antidepressants pyrazidol and inkazan on the effects of clonidine]. AB - The influence of Soviet-made antidepressants pyrazidol and incazane on some clonidine-induced effects (hypolocomotion, reactions of synchronization and desynchronization in the EEG, aggression) were studied. Pyrazidol and incazane reduce the effects of low doses of clonidine--the hypolocomotor one and the synchronization reaction in the EEG and enhance the effects of a high dose of clonidine--aggression and the desynchronization reaction in the EEG. The reduction of the sedative effects of clonidine as well as the enhancement of its activating effects by antidepressants can reflect the activation of adrenergic transmission by them. The adrenopositive effect of pyrazidol and incazane is more pronounced that that of imipramine. PMID- 1860491 TI - [The effect of diazepam on the free fatty acid content in the brain structures of rats with an experimental neurosis]. AB - The composition of free fatty acids of lipids in different rat brain structures (the cortex, hippocampus, striatum and midbrain) in neurosis was studied by the gas chromatographic analysis. The difference in their spectra was established. A pronounced increase of arachidonic acid content in the cortex (by 120%, p less than 0.01) and a statistically significant elevation of linolic acid level in all studied structures were noted. The levels of pentadecanoic and myristic acids were also changed. In neurosis diazepam (0.5 mg/kg, intraperitoneally, 40 minutes before the investigation) produced a decrease in the brain cortex of levels of arachidonic, oleic and myristic acids. In the hippocampus the contents of oleic and myristic acids increased. Less pronounced changes were found in the striatum and midbrain. PMID- 1860492 TI - [A pharmacological analysis of the mechanism of action of ethosuximide]. AB - Ethosuximide is one of the means of treatment of minor epilepsy but hardly any data on its mechanism of action are available in the literature. Anticonvulsant agents are known to bring about changes in the functions and in the interaction between some of the mediator systems within the central nervous system. An assessment of the status of neuromediator systems can be made on the basis of the response of isolated smooth muscle strips to the action of agonists and antagonists of various receptors. It was found by the pharmacological analysis of isolated strips from the rat stomach (antrum and corpus strips), the seminal duct and the cervical vein that ethosuximide induces a reduction in the physical contractile activity and the tone of smooth muscle preparations. Smooth muscle relaxation caused by ethosuximide is not blocked by different receptor inhibitors such as dihydroergotamine, propranolol, atropine, chlorpromazine, haloperidod and indomethacin. Ethosuximide causes a significant reduction in the physical contraction of smooth muscles produced by potassium chloride depolarization, with a stronger impact on the subsequent tonic contraction caused by calcium ions. A reduction in the potassium content of the solution has no effect on the nature of the action of ethosutimide. It is thus assumed that the probable mechanism of action of ethosuximide consists in lowering calcium transport since the inhibitors of calcium transport sodium nitroprusside and verapamil intensify the blocking effect of ethosuximide on smooth muscle contractile activity. PMID- 1860493 TI - [The effect of ecdysterone on experimental arrhythmias and changes in the hemodynamics and myocardial contractility induced by coronary artery occlusion]. AB - In acute animal experiments it was shown that phytoecdizon ecdisteron (ecdisten) in some animals eliminates arrhythmia caused by the ligation of the descending branch of the left coronary artery and prevents the development of fibrillation and also corrects the hemodynamic parameters and the structure of the heart contractility, prevents the development of arrhythmias induced by aconitine and calcium chloride. The mechanism of the antiarrhythmic action is related to the membrane stabilizing effect and the improvement of the hemodynamic parameters and the heart contractility is due to an increase of the adaptative possibilities of the myocardium. PMID- 1860494 TI - [The clinico-pharmacological characteristics of anteovin]. AB - The clinical and laboratory studies carried out on 160 women showed a high contraceptive effect and good tolerance of anteovine. The contraceptive effect of the biphasic drug is determined by its antiovulatory action concurrent with inhibition of the basal periovulatory secretion of gonadotropins and secretion of sex hormones. PMID- 1860496 TI - [The immunomodulating action of thymopentin in acute and chronic stress]. AB - Thymopentin, an active centre of the thymic hormone, was shown to possess a marked immunomodulatory effect on the cellular immune reactions of immunity in rats under acute and chronic stress. Thymopentin ensures adaptation of the organs of immunogenesis by increasing viability of the polymorphonuclear leukocytes and normalization of the phagocytic activity of the leukocytes. PMID- 1860497 TI - [The effect of sulfur-containing preparations on the development of immediate allergization]. AB - The effects of sulfur-containing drugs and an inhibitor of sulfhydryl groups on the development of allergization of immediate type were studied. In experiments on rabbits and guinea pigs it was shown that the effects of sulfur-containing drugs depend on the dose, the stage of the allergic process. The donors of sulfhydryl groups significantly reduce anaphylactic shock and repeated allergic reactions of immediate type. The inhibitor of sulfhydryl groups produces the dose dependent increase or decrease of the allergic reaction. The studied drugs change the dynamics of the content of sulfhydryl groups during sensitization. PMID- 1860495 TI - [The chlorine e6-photosensitized inhibition of human thrombocyte aggregation]. AB - ADP-induced aggregation of platelets in the presence of chlorin E6 under the action of visible light depending on the pigment concentration and the time of light action was studied. It was shown that the photosensitized effect of chlorin E6 on the platelet-enriched plasma results in platelet aggregation inhibition. PMID- 1860498 TI - [The pharmacokinetic and pharmacodynamic characteristics of diazepam in different populations of rats]. AB - Significant differences in diazepam pharmacokinetics in different populations of rats both within one family and within one species were revealed. A high degree of correlation between the pharmacokinetic parameters and pharmacodynamic indices indicates that the myorelaxant effect is in a direct dependence on diazepam concentration in the rat organism. PMID- 1860499 TI - [The dynamics of the body distribution of heparin and its antagonist, the quaternary ammonium salt of conidine oligomer-25, when administered via the lungs]. AB - The distribution in the organism of radioactivity after intratracheal administration of labelled heparin and its quarterly ammonium salt oligomer-25 conidine was studied. Within 25 hours the preservation of a high level of radioactivity in plasma, its decrease in other investigated organs and the accumulation in mast cells of the peritoneal cavity were observed. The involvement of the lymphatic system in heparin metabolism was shown. A positively charged oligomer conidine administered intratracheally, in contrast to heparin, was not detected in blood plasma in the studied time. The accumulation of the drug in the lung tissue, lymph nodes and excretory organs was noted. PMID- 1860500 TI - [The effect of x-ray contrast media on the spontaneous hemolysis of human erythrocytes and the possible regulatory pathways]. AB - It was shown that bilignost, in contrast to triombrast, iodamide and metrizamide precipitates spontaneous hemolysis of human erythrocytes. The hemolytic effect of bilignost may be decreased by means of pipolphen and prednisolone or by using the mixture of albumin + glycerin + sodium chloride + bilignost. PMID- 1860501 TI - [Acebutolol and diacetolol: their binding to plasma proteins and erythrocytes and secretion with the saliva]. AB - Thirty-two patients with hypertensive disease were treated with a cardioselective blocker of beta-adrenergic receptors acebutolol ("Sectral-400", Rhone Poulenc, France). The binding of the drug and its metabolites diacetolol to plasma proteins and erythrocytes and their excretion with the saliva were studied. The significant binding of acebutolol and diacetolol to erythrocytes was shown. The ratio of the content of the free form of these substances in erythrocytes to plasma content was on the average 1.54 +/- 0.96 for diacetolol and 1.93 +/- 1.01 for acebutolol. A good correlation of acebutolol and diacetolol contents in the saliva with their contents in plasma was found. The mean values of the protein bound fraction were for acebutolol 0.133 +/- 0.038 and for diacetolol 0.106 +/- 0.050. PMID- 1860502 TI - [Propranolol binding with plasma proteins and erythrocytes]. AB - The binding of propranolol with plasma proteins and erythrocytes after oral administration of 80 mg of anapriline was studied in 12 patients with hypertensive disease. The content of propranolol fraction bound to plasma proteins was on the average 0.84 +/- 0.4. It was shown that propranolol to a considerable degree is captured by erythrocytes. The ratios of the erythrocyte content of propranolol free form to the plasma content were on the average 3.72 +/- 0.92 and 2.70 +/- 1.20, respectively, 2 and 4 hours after anapriline intake. During the assessment of the pharmacological parameters it is recommended to determine the contents of the total and free forms of propranolol in the whole blood rather than in plasma. PMID- 1860503 TI - [The clinical pharmacokinetics of kemantane]. AB - The pharmacokinetics of a new Soviet-made immunostimulant kemantane, a derivative of adamantine, was studied by gas-liquid chromatography in patients with bronchial pathology. It was found that in the blood of the patients kemantane was not practically detected due to a pronounced effect of the "first pass" through the liver. Kemantane kinetics was evaluated by the kinetics of its major active metabolite. On the basis of the performed studies the scheme of using kemantane in the patients with decreased immunity was recommended. PMID- 1860504 TI - [A preclinical study of the embryotoxic properties of cucumarioside and its effect on adult generative function]. AB - The preclinical study of embryotoxicity of a new immunomodulator cucumariosid was carried out. Cucumariosid at long-term use exerts no effect on the generative function of rats, the general condition of pregnant females and the postnatal development of the offspring, possesses no teratogenic action. The use of the drug in the preimplantation period of pregnancy and the implantation period produces the contraceptive effect. PMID- 1860505 TI - [A behavioral and biochemical analysis of the therapeutic effect of sodium oxybutyrate in alcoholic encephalopathy in progeny]. AB - The alcoholization of pregnant female rats (5 g/kg) results in a decrease of endogenous ethanol level in their offspring and distant disturbances of the conditioned reflex activities of the young rats deteriorating the formation and preservation of the skill with an emotional positive reinforcement. Sodium gamma gydroxybutyrate administered in a dose of 50 mg/kg from the 8th to the 20th day of life prevents the above-mentioned disturbances of learning and memory, restores the level of endogenous ethanol, corrects the parameters of lipid and mediator metabolism in the brain and blood changed by prenatal alcoholization. PMID- 1860507 TI - [The effect of antenatal exposure to the bacterial lipopolysaccharide prodigiozan on the neurons of the ganglionic layer of the sensorimotor cortex in 30-day-old rats]. AB - A single administration of prodigiosan to pregnant albino rats in a dose of 100 micrograms/kg was shown to exert the adverse effect on energy and plastic metabolism of neurocytes of the cerebral ganglionic layer in their offspring. These properties were most pronounced at administration on the 14th and 18th days of pregnancy. PMID- 1860506 TI - [The lithium oxybutyrate correction of disorders in higher nervous activity in the progeny of alcoholized male rats]. AB - In experiments on rats it was shown that alcohol administered intragastrically in a dose of 8 g/kg for 4 weeks produced long-term disturbances of CNS function in the offspring similar to those observed under clinical conditions. Early postnatal administration of lithium oxybutyrate (from the 8th through the 14th day of life) was found to prevent the development of the disturbances. PMID- 1860508 TI - [Calculation of the standard error of the effective dose ratio]. PMID- 1860509 TI - [Blood plasma proteins and drug transport across the hemato-encephalic barrier]. AB - The blood-brain barrier being a dynamic membrane interface between the blood and the brain is of great importance for the formation of the pharmacokinetics and pharmacodynamics of neurotropic drugs. One of the main factors influencing diffusion of drugs into the central nervous system is the degree of their binding by plasma proteins. It was supposed that only the unbound fraction of drugs is pharmacologically active. However in some papers the plasma-protein-mediated transport into the rat brain of endogenous compounds and drugs was demonstrated. This indicates that the measuring of the free fraction of a drug in vitro can lead to the underestimation of its concentration in the target organ. PMID- 1860510 TI - [The mechanisms of the hepatotoxicity of paracetamol]. PMID- 1860511 TI - [The effect of N-acetylaspartic acid on the processes of memory and learning in rats]. AB - The effects of a neurospecific substance N-acetyl-aspartic acid on memory and learning processes were investigated after intraperitoneal and oral administrations in rats. N-acetyl-aspartic acid was shown to restore the passive avoidance reaction in electroshock and scopolamine amnesias as well as in natural extinction. Chronic injections of N-acetyl-aspartic acid improved the learning in water maze but exerted no effect on the acquisition and retention of the active avoidance reaction in the shuttle box. PMID- 1860512 TI - [The use of antioxidants for treating tuberculosis patients]. PMID- 1860513 TI - [Information on new books on the problems of pharmacology and related disciplines]. PMID- 1860514 TI - TIA in a middle-aged smoker. PMID- 1860517 TI - The University of Delaware/Jefferson Medical College Medical Scholars Program: an approach to educating physicians for academic leadership and practice. PMID- 1860515 TI - Heart disease associated with deletion of the short arm of chromosome 18. AB - Deletion of the short arm of chromosome 18 provides a highly variable phenotype. Mental retardation, short stature, and abnormal facies are invariably present. About 9 percent of patients with this syndrome have cardiac pathology. An additional case with congenital heart disease has been presented along with a review of the literature concerning the association of congenital heart disease and the 18p- syndrome. PMID- 1860516 TI - Family-centered short-term rehabilitation for severe childhood asthma. PMID- 1860518 TI - A narrative of the Patricia James case. PMID- 1860519 TI - Endometrial ablation offers alternative to hysterectomy. PMID- 1860520 TI - Legal issues in hospital-physician joint ventures. PMID- 1860521 TI - Concepts of radiation safety and protection: beyond BEIR V. AB - The publication of an updated report on the biological effects of ionizing radiation (BEIR V) has focused new attention on the potential hazards associated with the use of low doses of ionizing radiation for diagnostic purposes. This article reviews the BEIR V report findings and suggests methods for reducing the risks to dental patients and the operators of dental x-ray equipment. PMID- 1860522 TI - Update on restorative materials. PMID- 1860523 TI - Vacuuming a mercury-contaminated dental office may be hazardous to your health. AB - Exposure to mercury contamination in the dental office poses a potential hazard for dental personnel. Although many precautions for containing the poisonous metal vapors are routinely observed, dental personnel may place themselves at risk by failing to use proper cleaning techniques. Researchers from the National Institute for Occupational Safety and Health (NIOSH) have discovered that vacuum cleaners designed for the home are sometimes used to clean dental office carpets, which might be contaminated with mercury. Since ordinary vacuum cleaners increase airborne mercury concentrations, dental personnel should use a specially designed vacuuming system for mercury recovery. PMID- 1860524 TI - Pediatric behavior management: the dental assistant's role. PMID- 1860525 TI - The office manual: backbone of the dental practice. PMID- 1860526 TI - Record taking in the orthodontic office. PMID- 1860528 TI - [Restoration of an upper jaw with pre-manufactured Duo-lock attachments]. PMID- 1860527 TI - Management of infectious waste. PMID- 1860529 TI - [Characterizing of denture teeth. Variations of shape and characteristics]. PMID- 1860530 TI - [Experience with the extra-coronal anchor Bego Clip P]. PMID- 1860531 TI - [Practical experiences with the Isosit inlay/onlay material]. PMID- 1860532 TI - [Harmony of shape and color in combined tooth replacements]. PMID- 1860533 TI - [Total prosthetics after a biogenetic example--double impression taking and intraoral bite registration]. PMID- 1860534 TI - [The making of fireproof dies with the duplicating system according to Rath]. PMID- 1860535 TI - [Is dry trimming a real improvement in model making?]. PMID- 1860536 TI - [Implant retained hybrid prosthesis with Supra-Snap anchor element]. PMID- 1860537 TI - [Repair of defective secondary telescope combination denture]. PMID- 1860538 TI - [Gold-colored titanium nitride coating of non-precious metal adhesive bridge]. PMID- 1860539 TI - [Technical preparation of Sander feather activator]. PMID- 1860540 TI - [Milling technique and spark erosion, an alternative to cast titanium]. PMID- 1860541 TI - [Systematic for milling technique of anterior tooth precision attachment]. PMID- 1860542 TI - [Model measuring, mounting on Gnathomat, tooth set-up]. PMID- 1860544 TI - Beating burn-out. PMID- 1860543 TI - [Surface treatment of silver-palladium and reduced precious metal alloys]. PMID- 1860545 TI - TMJ malpractice: are you at risk? PMID- 1860546 TI - How to remember patients' names. PMID- 1860547 TI - Dentistry 1991: the bright side. An interview with Barry Waldman. PMID- 1860548 TI - The benefits of laser dentistry. PMID- 1860549 TI - Protect your office from embezzlement. PMID- 1860550 TI - The best dentist you can be: the Pankey experience, Part V. PMID- 1860551 TI - Local anesthetics. PMID- 1860552 TI - Release of amylin from perfused rat pancreas in response to glucose, arginine, beta-hydroxybutyrate, and gliclazide. AB - Amylin is a 37-amino acid peptide isolated from the islet amyloid of patients with non-insulin-dependent diabetes mellitus. The isolated perfused normal rat pancreas was used to evaluate the effects of glucose and insulin secretagogues, such as arginine, beta-hydroxybutyrate, and gliclazide, on amylin secretion. Glucose and the other stimulants tested elicited a significant release of amylin from the rat pancreas in a biphasic pattern, similar to that of insulin. Dose response studies of the glucose-induced release of amylin and insulin revealed that they possessed a similar dependency on glucose. However, the release of amylin induced by high concentrations of glucose was partially dissociated from that of insulin; that is, the amylin-insulin molar ratios induced by 22.2 and 33.3 mM glucose (1.11 +/- 0.05 and 1.05 +/- 0.04%, respectively) were significantly higher than those induced by 16.7 mM glucose (0.90 +/- 0.04%, P less than 0.01 vs. 22.2 mM glucose, P less than 0.05 vs. 33.3 mM glucose). Additionally, when the basal concentration of glucose in the perfusate was increased from 5.6 to 11.1 mM, the response of amylin was unchanged. These data suggest that amylin may be an islet hormone whose abundant response to high concentrations of glucose might contribute to the oversecretion of amylin in the hyperglycemia that accompanies diabetes mellitus. PMID- 1860553 TI - Trans-hydroxyl group configuration on carbons 2 and 3 of glucose. Responsible for acute inhibition of myo-inositol transport? AB - Cultured neuroblastoma, cerebral microvessel endothelial, and retinoblastoma cells were used to examine the mechanism of acute inhibition by D-glucose of myo inositol uptake. Acute exposure of the cells to 30 mM D-glucose caused a significant decrease in Na(+)-dependent myo-inositol uptake in all three cell types. The effect of D-glucose to acutely inhibit myo-inositol uptake was dependent on the extracellular glucose concentration and was not reversed by sorbinil. 2-Deoxy-D-glucose (30 mM), 3-O-methyl-D-glucose (30 mM), and cytochalasin B (100 microM) did not acutely inhibit myo-inositol uptake. These data suggest that the hydroxyl groups on carbons 2 and 3 of D-glucose, which in a Haworth projection appear trans to each other, are important for inhibitory activity. Other monosaccharides (30 mM) having a similar 2,3-trans-diol configuration, L-glucose, D- and L-fucose, D- and L-galactose, D- and L-xylose, and D-arabinose, all to varying degrees significantly inhibited myo-inositol uptake. In all cases, the L-isomers were more potent inhibitors of myo-inositol uptake than the corresponding D-isomers. Monosaccharides (30 mM) having hydroxyl groups on carbons 2 and 3 in a cis configuration, D-mannose, L-rhamnose, D allose, and D-ribose, did not acutely inhibit myo-inositol uptake. Replacing the hydroxyl group with a fluorine on carbons 2 or 3 of D-glucose negated its inhibitory activity of myo-inositol uptake. In contrast, replacing the hydroxyl group with a fluorine on carbon 6 of D-glucose did not block its inhibition of myo-inositol uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860554 TI - Insulin and glucose levels and prevalence of glucose intolerance in pedigrees with multiple diabetic siblings. AB - Hyperinsulinemia may be an early inherited marker for a defect in insulin action that subsequently results in glucose intolerance and non-insulin-dependent diabetes mellitus (NIDDM). To examine the role of hyperinsulinemia in individuals at high genetic risk for NIDDM and determine the prevalence of impaired glucose tolerance (IGT) and newly diagnosed diabetes in members of NIDDM pedigrees, we studied 310 members of 16 pedigrees ascertained for greater than or equal to 2 NIDDM siblings. Nondiabetic members of all pedigrees were examined by 75-g oral glucose tolerance test with fasting and 1-h insulin levels. Participants had height and weight recorded. Spouses of pedigree members (n = 88) served as control subjects. The spouse control subjects were older and slightly more obese than the undiagnosed pedigree members. The prevalence of IGT was 14.8% in spouses and 7.7% in pedigree members, and NIDDM was present in 11.3% of spouses and 2.3% of previously undiagnosed pedigree members. However, neither spouses nor pedigree members differed significantly from published age-specific prevalence rates for IGT or newly diagnosed NIDDM. Insulin and glucose levels were examined in pedigree members with normal glucose tolerance (NGT). Fasting insulin levels were not significantly different between spouses and NGT pedigree members. However, after adjustment for age, weight (body mass index), and sex, NGT pedigree members had higher 1-h insulin levels and higher fasting and 1-h glucose levels than spouses. These differences were also evident when pedigree members with at least 1 affected (NIDDM or IGT) parent were compared with spouses with no family history of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860556 TI - Induction of islet cytodifferentiation by fetal mesenchyme in adult pancreatic ductal epithelium. AB - Recombinant tissue consisting of adult ductal epithelium isolated from pancreas and fetal mesenchyme was transplanted subcutaneously in the inguinal region of nude mice or epididymal fat pads of rats with a tissue chamber device for short term (8-day) or long-term (6- to 12-wk) duration. We found that recombinant tissue underwent morphogenesis and cytodifferentiation, thereby forming islets that contained cells immunocytochemically positive for insulin and glucagon. Islet cytodifferentiation occurred in approximately 20% of the recombinants. In recombinants that developed into islets, the tissue was always in close association with an extracellular matrix, nerves, and blood vessels. Controls consisting of mesenchyme alone or duct epithelium alone showed no evidence of morphogenesis of cytodifferentiation. Pancreatic rudiments were also implanted to serve as positive controls. This is the first demonstration of islet cytodifferentiation from adult duct epithelium. PMID- 1860555 TI - Evidence for dual control mechanism regulating hepatic glucose output in nondiabetic men. AB - We previously reported a fall in hepatic glucose output (HGO) during sleep accompanied by reductions in glucose utilization (Rd) and free fatty acids (FFAs). This study was undertaken to determine the potential role of changes in Rd and FFA on HGO in nondiabetic men. To determine if the fall in HGO during sleep could be reversed by FFA elevation, seven nondiabetic men underwent [3 3H]glucose infusions from 2200 to 0800, with heparin (90 mU.kg-1.min-1) added at 0200. Glucose appearance (Ra) fell from 11.7 +/- 1.1 at 2430 to 8.9 +/- 0.8 mumol.kg-1.min-1 (P less than 0.05) at 0200. The fall in Ra was associated with decreases in FFA (0.57 +/- 0.10 to 0.48 +/- 0.07 mM) and glycerol (0.08 +/- 0.01 to 0.06 +/- 0.01 mM). Infusion of heparin significantly increased FFA and glycerol (1.09 +/- 0.21 and 0.11 +/- 0.01 mM, respectively, P less than 0.01) and resulted in a significant fall in plasma alanine, suggesting that gluconeogenesis had been increased. However, rates of glucose turnover were indistinguishable from overnight studies without heparin. In additional studies (n = 6), intralipid and heparin-induced FFA elevation (from 0.61 +/- 0.07 to 0.95 +/- 0.05 mM, P less than 0.01) stimulated gluconeogenesis ([U-14C]alanine to glucose) twofold (188 +/ 22% increase compared to 114 +/- 6% in saline control studies, P less than 0.01). However, despite increasing gluconeogenesis, overall HGO did not change (10.6 +/- 0.5 vs. 10.7 +/- 0.6 mumol.kg-1.min-1) during lipid infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860557 TI - Importance of insulin in subjective, cognitive, and hormonal responses to hypoglycemia in patients with IDDM. AB - Not all episodes of hypoglycemia are recognized as such by diabetic patients, suggesting that it is possible for them to adapt to a low blood glucose level, although the mechanism involved is not known. The aim of this study was to examine whether insulin has an effect, independent of blood glucose, on the subjective, cognitive, and hormonal responses to hypoglycemia. Nine patients with insulin-dependent diabetes mellitus (IDDM) participated in three hyperinsulinemic glucose-clamp studies. After 60 min at 4.5 mM, blood glucose was randomized to be 1) maintained at 4.5 mM for 240 min, 2) lowered to 2.8 mM for 180 min followed by 60 min at 2 mM with an insulin infusion rate of 40 mU.m-2.m-1, and 3) fitted to the same protocol as 2 but with an infusion rate of 120 mU.m-2.min-1. Symptoms and awareness of hypoglycemia (100-mm visual analogue scales), cognitive function, and counterregulatory hormone levels were assessed every 30 min. There were no subjective or cognitive changes during the euglycemic study. Awareness and hypoglycemic symptoms (hunger, facial flushing, trembling, and sweating) were attenuated by the higher insulin infusion rate (P less than 0.05 and P less than 0.01, respectively). Cognition was significantly impaired after 60 min at 2.8 mM (P less than 0.001) and deteriorated further when the blood glucose level was lowered to 2 mM (P less than 0.01). Levels of cortisol (P less than 0.01) and growth hormone (P less than 0.05) but not epinephrine were suppressed by the higher insulin infusion rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860558 TI - Prediction and prevention of IDDM--1991. AB - Although we can now identify some nondiabetic individuals who will subsequently develop clinical insulin-dependent diabetes mellitus (IDDM), our ability to predict subsequent clinical IDDM is far from perfect. In this article, we discuss the status of knowledge regarding the natural history of preclinical IDDM and discuss, especially in relation to predicting IDDM, the genetic, immunologic, and metabolic components of the IDDM disease process. PMID- 1860559 TI - Antagonistic effect of human alpha-calcitonin gene-related peptide (8-37) on regional hemodynamic actions of rat islet amyloid polypeptide in conscious Long Evans rats. AB - Rat synthetic amidated islet amyloid polypeptide (IAPP) was infused into conscious Long-Evans rats chronically instrumented for the measurement of regional hemodynamics. Rat IAPP (0.25-2.5 nmol.kg-1.min-1) had dose-dependent tachycardiac and hypotensive effects. Renal blood flow increased at all dose levels in association with incremental rises in renal vascular conductances. Hindquarters blood flow and vascular conductance increased at the higher dose levels, but mesenteric blood flow fell with mean arterial blood pressure (i.e., there was no change in mesenteric vascular conductance). Concurrent infusion of 25 nmol.kg-1.min-1 human alpha-calcitonin gene-related peptide (CGRP) (8-37) abolished the hypotensive, tachycardiac, and renal and hindquarters vasodilator effects of rat IAPP, and during administration of both peptides, there was a transient renal and sustained mesenteric vasoconstriction. When the infusion of human alpha-CGRP (8-37) was stopped, the effects of the continued infusion of rat IAPP were reestablished. The results indicate that the reported ability of IAPP to induce insulin resistance cannot be due to decreased skeletal muscle blood flow. In addition, human alpha-CGRP (8-37) is an effective antagonist of the hemodynamic actions of rat IAPP. Because it has been shown previously that human alpha-CGRP (8-37) antagonizes the hemodynamic effects of human alpha-CGRP, these results, collectively, indicate that human alpha-CGRP and rat IAPP might act on the same receptor at which human alpha-CGRP (8-37) is an effective antagonist or that the latter is a nonselective antagonist of separate receptors on which human alpha-CGRP and rat IAPP act. PMID- 1860560 TI - Abnormalities of cognitive functions in IDDM revealed by P300 event-related potential analysis. Comparison with short-latency evoked potentials and psychometric tests. AB - The possible influence of diabetes on the higher mnestic and cognitive functions has been investigated. The P300 wave latency, an endogenous electrophysiological event, was explored and compared with the multimodal short-latency evoked potential (EP) recordings (visual [VEP], brainstem auditory [BAEP], and median and tibial nerve somatosensory EPs [mSEP and tSEP, respectively]) and psychometric test measures in 16 insulin-dependent diabetic (IDDM) patients, in 16 age- and (IDDM) sex-matched nondiabetic subjects, and in a large normal reference population. The age of subjects, the duration of IDDM, and the metabolic control of patients were taken into account. P300 values were significantly increased in IDDM versus matched control subjects (P less than 0.001), and 3 patients showed values above the reference value range. Abnormal VEP recordings were present in 1 of 16 patients, BAEP in 3 of 16, mSEP in 7 of 16, and tSEP in 6 of 16. Digit-span backward test results were significantly (P less than 0.02) modified in the diabetic cohort. There was no tendency for anomalies of P300, short-latency EPs, and psychometric test values to be contemporarily present, except in 1 patient. Electrophysiological or psychometric abnormalities were not clearly correlated with the duration of IDDM or the degree of short-term metabolic control. These findings give evidence that 1) higher cognitive functions may be affected in diabetes as documented by P300 analysis and short-term memory tests, 2) endogenous electrophysiological analysis highlights neuropsychological changes not detectable by psychometric tests, 3) an alteration of evoked potentials was present in half of the IDDM subjects studied, and 4) anomalies of the CNS are patchily distributed in diabetes. PMID- 1860561 TI - Inducement of antibody that mimics insulin action on insulin receptor by insulin autoantibody directed at determinant at asparagine site on human insulin B chain. AB - We previously showed that purified human IgG1 insulin autoantibody (IAA) from the serum of male patient T.H. with insulin autoimmune syndrome is directed at a determinant at the asparagine site on the human insulin B chain. An anti idiotypic antibody (anti-TH) that inhibited TH-IAA binding to human insulin was obtained by immunizing BALB/c mice with TH-IAA. Anti-TH bound to viable IM-9 cells and the purified insulin receptor from IM-9 cells. Anti-TH binding to IM-9 cells and the insulin receptor was inhibited by TH-IAA but not by human IgG. Moreover, incubation of HepG2 cells with anti-TH had an inhibitory effect on insulin binding to HepG2 cells. Anti-TH, like insulin, stimulated amino acid uptake in HepG2 cells. These findings indicate that the conformation of TH-IAA idiotope is a mirror image of the determinant on the insulin B chain, the binding site for TH-IAA on anti-TH is also related to the insulin binding site on the insulin receptor, and anti-TH mimics insulin action on the insulin receptor. PMID- 1860562 TI - Progression to type I diabetes in autoimmune endocrine patients with islet cell antibodies. AB - In an 11-yr screening program carried out on serum samples sent to an autoimmune serology laboratory, 158 patients with clinical or subclinical autoimmune endocrine manifestations and islet cell antibodies (ICAs) in the absence of overt diabetes were identified and followed for the development of insulin-dependent (type I) diabetes. Twenty-two (13.9%) developed type I diabetes in a follow-up of up to 12 yr (mean +/- SE 4.8 +/- 3.2 yr). The probability of being free of type I diabetes was 69.8% at 10 yr after the first detection of ICAs. Progression to disease was influenced by 1) the amount of ICAs represented by high titers (63% of those with ICAs greater than or equal to 20 Juvenile Diabetes Foundation units being free of type I diabetes at 10 yr), ICA persistency (59% being free of type I diabetes; P less than 0.02 vs. nonpersistent ICA), and complement-fixing (CF) ICAs (63% being free of type I diabetes; P less than 0.05 vs. non-CF-ICA); 2) the coexistence of insulin autoantibodies (IAAs) (25% being free of type I diabetes; P less than 0.005 vs. IAA-); and 3) a positive family history (1st-degree relative) for type I diabetes (32% being free of type I diabetes; P less than 0.005 vs. no family history). There was a trend for diabetes to develop earlier in males of a younger age. No relationships were found with the number, type, or clinical expression of the associated autoimmunities or with a family history of such disorders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860563 TI - Relative hypersecretion of proinsulin in rat model of NIDDM. AB - The plasma ratio of proinsulin to insulin is raised in individuals with non insulin-dependent diabetes mellitus (NIDDM). Increased secretion of proinsulin relative to insulin is thought to be the cause, although differential changes in clearance have not been ruled out. This study was conducted in a rat model of NIDDM, 90% pancreatectomized (Px) rats, to investigate the pathophysiology of this observation. Proinsulin storage and secretion were assessed with high performance liquid chromatography separation of the insulins and the proinsulins, followed by quantification of the peaks by insulin radioimmunoassay. In Px rats, the relative proportion of proinsulin in pancreas extracts was twice that of control (sham-operated) rats (15.6 +/- 1.4 vs. 8.3 +/- 1.4%, P less than 0.01). Samples obtained from the portal vein during in vitro pancreas perfusion also had an elevated proinsulin fraction (Px, 10.3 +/- 3.0; sham, 3.0 +/- 0.6%; P less than 0.006). In summary, 90% Px rats share many pathophysiological features with NIDDM, including loss of normal proinsulin homeostasis. Our results suggest that chronic hyperglycemia causes an intrinsic change in beta-cells that is characterized by the increased storage and secretion of proinsulin. PMID- 1860565 TI - [The modelling of the development of respiratory muscle force during forced expiration]. PMID- 1860564 TI - Lack of effect of islet amyloid polypeptide in causing insulin resistance in conscious dogs during euglycemic clamp studies. AB - In this study, we administered constant intravenous infusions of human islet amyloid polypeptide (hIAPP) to conscious dogs during euglycemic glucose-clamp studies. The doses of hIAPP used (5 and 50 pmol.kg-1.min-1) raised the circulating IAPP levels approximately 12- and 50-fold above basal levels, respectively. Studies were conducted at two different insulin infusion rates, resulting in steady-state plasma insulin levels of approximately 600 and 2800 pM. According to our results, the hIAPP infusions did not lead to any measurable change in the insulin-stimulated glucose disposal rate at either insulin infusion rate. Additionally, we observed no effect of IAPP on hepatic glucose production. Although we did not observe any effect of hIAPP on any of the aspects of glucose or insulin metabolism measured, we did find a consistent hypocalcemic effect of this peptide at the 50-pmol.kg-1.min-1 infusion rate. Shortly after the onset of hIAPP infusion, serum calcium levels fell by 10-15% and remained at these levels throughout the course of the hIAPP infusion. In summary, 1) infusion of hIAPP at doses of 5 or 50 pmol.kg-1.min-1 in conscious dogs raised the circulating IAPP level 12- to 50-fold above basal; 2) during these infusion studies, no effect of hIAPP was observed on any of the aspects of glucose or insulin homeostasis measured; 3) 50 pmol.kg-1.min-1 hIAPP lead to a prompt reduction in plasma calcium concentrations with intravenous administration. PMID- 1860566 TI - [Maximum lung ventilation and its mobilization under physical loads]. PMID- 1860567 TI - [The use of the plant preparations Valdai and Al'tair for enhancing the functional potentials of athletes]. PMID- 1860568 TI - [The use of automated systems for assessing the health of workers. I. The study of the indices of the functional status of different occupational groups]. PMID- 1860570 TI - [The effect of a clinical adrenaline dose on the concentration of gonadotropins and antidiuretic hormone in the blood of healthy subjects of different ages]. PMID- 1860569 TI - [Circadian fluctuations in bivalent electrolytes, calcitonin and parathyroid hormone in the serum of healthy subjects]. PMID- 1860572 TI - [The electrical potential asymmetry of the human body]. PMID- 1860571 TI - [Changes in human hormonal and immune indices under low temperatures]. PMID- 1860573 TI - [The use of a 3-factor model for describing accentuated forms of behavior]. PMID- 1860574 TI - [The dynamics of the electroencephalographic indices of 6-year-old children under the influence of school instruction]. PMID- 1860575 TI - [The effect of breathing exercises via supplementary "dead" space combined with physical loading on the duration of voluntary apnea and on the external respiratory function]. PMID- 1860576 TI - [A factor model of the meteorotropic reactivity of physically trained and untrained subjects]. PMID- 1860577 TI - [The factor structure of the EEG spectrum of the left and right hemispheres of the human brain at rest and during the processing of visual information]. PMID- 1860578 TI - [The liver and kidney blood circulation during local decompression of the abdominal cavity]. PMID- 1860579 TI - [Changes in energy metabolism under the influence of an insulin administration test]. PMID- 1860580 TI - [A method for recording short-latency auditory evoked potentials based on the DVK 3 microcomputer]. PMID- 1860581 TI - [A comparison of the results of dynamic neuropsychological and electroencephalographic research on neurosurgical patients with optic nerve lesions]. PMID- 1860582 TI - [The object of perception and interference resistance in the auditory system]. PMID- 1860583 TI - [The dependence of human psychophysiological reactions on the spatial-temporal organization of local proprioceptor stimuli]. PMID- 1860584 TI - [The formation of interhemispheric interaction in ontogeny. An electrophysiological analysis]. PMID- 1860585 TI - [An evaluation of the statistical characteristics of the spatial coherence of the bioelectrical processes in the human brain. II. Electrosubcorticogram research on epilepsy patients]. PMID- 1860587 TI - [The transient modes of sinoatrial node work during typical excitation exposures]. PMID- 1860586 TI - [The dependency of functional testing results on the degree of left ventricular failure and the localization of the myocardial lesion in patients with ischemic heart disease]. PMID- 1860588 TI - [Human temperature regimens under hypothermic protection during operations on the heart (research on a mathematical model)]. PMID- 1860589 TI - [The reaction to hypoxia of the human and animal organisms in relation to the individual characteristics of their autonomic nervous systems]. PMID- 1860590 TI - [Body resistance in participants in polar expeditions]. PMID- 1860591 TI - [The possibilities for the statistical evaluation of central nervous system reactivity and homeostasis in healthy subjects and patients with brain lesions]. PMID- 1860592 TI - [The peripheral blood of the native inhabitants of eastern Siberia]. PMID- 1860593 TI - [The characteristics of human adaptation to the effect of moderate high-altitude hypoxia and hyperthermia during the performance of a physical load]. PMID- 1860595 TI - [Dependence of flight training on the individual characteristics of the students]. PMID- 1860594 TI - [Heat perception during the seasonal adaptation to high temperature]. PMID- 1860596 TI - [Experience in using automatic systems for assessing the functional characteristics of the body. II. The indices of autonomic regulation in athletes of different sports specialties and levels of the physical work capacity of the body]. PMID- 1860597 TI - [Physiological approaches to setting standards for body stress in work]. PMID- 1860598 TI - [Overcoming the traditions that have built up in electroencephalography]. PMID- 1860599 TI - [Biorhythmological approaches to the study of functional asymmetry in the equilibrium and spatial orientation systems]. PMID- 1860600 TI - [Means for optimizing impedance measuring methods in hemodynamic research]. PMID- 1860601 TI - [An analysis of the autonomic regulation of cardiac rhythm at different stages in individual human development]. PMID- 1860602 TI - [The potential opportunity for radiokinetocardiography in research on the movements of the cardiac structures and walls of the large vessels]. PMID- 1860603 TI - [The patterns of a change in the subjective time standard]. PMID- 1860604 TI - [The use of peripheral pulse indices for the differential diagnosis of lung diseases]. PMID- 1860605 TI - [The dynamics of transcutaneous oxygen tension in detecting the anaerobic threshold under increasing physical loads]. PMID- 1860606 TI - [Respiratory functions during speech activities]. PMID- 1860607 TI - [An analysis of the processes facilitating the tendon reflex by Jendrassik's maneuver]. PMID- 1860608 TI - [The contractile properties of the anterior tibial muscle in athletes of different sports specialties and in nonathletes]. PMID- 1860609 TI - [The role of the number of movements in the perception of the position of the parts of the body]. PMID- 1860610 TI - [The circadian dynamics of the hormonal regulation of human water-salt exchange during long-term hypokinesia]. PMID- 1860611 TI - [The effect of a cooling water environment on the hormonal status of the human body]. PMID- 1860612 TI - The health of U.S. science. PMID- 1860613 TI - Contrasting work environments of medical school faculty. AB - An attitude survey has revealed vividly contrasting institutional atmosphere and working conditions at U.S. medical schools. Environments at about one-fourth of the schools were judged to be highly positive with regard to subjective atmosphere, career development, and faculty-administration relations. Environments at another one-fourth of all schools were judged to be highly negative in all of these areas. Recognizing the existence of these differences is necessary before administrative remedies for many of the problems at the latter group of schools can be implemented. PMID- 1860614 TI - Molecular studies of the uncoupling protein. AB - The uncoupling protein (UCP) is a proton/anion transporter found in the inner mitochondrial membrane of brown adipocyte. Although UCP has not been detected in mitochondria from any other tissue, it shares structural and catalytic properties with several other mitochondrial carrier proteins. Although UCP was discovered only recently it is one of the most extensively studied mitochondrial carrier proteins. Many tools useful in research on UCP have been developed such as antibodies and cDNAs corresponding to UCP of several animal species. More recently, the mouse, rat, and human genes encoding for UCP have been isolated and sequenced. The availability of these various tools has led to several significant observations. UCP gene expression is strongly controlled at the level of transcription by signals that are activated after the stimulation of brown adipocytes by norepinephrine. The comparison of UCP gene with the genes encoding the adenine nucleotide translocator revealed the existence of structural and evolutionary homologies. Moreover, in humans the UCP gene and one form of adenine nucleotide translocator gene are located on the same chromosome. Recently, the expression of functional UCP in various heterologous systems was achieved (Xenopus oocytes, CHO cells, yeasts). These data will facilitate studies of the structure/function relationship in UCP (identification of residues involved in H+ transport, Cl- transport, nucleotide binding, mitochondrial targeting...). Another aspect of the present research on UCP is the understanding of mechanisms that control the UCP gene and the differentiated commitment of adipose precursor cells to thermogenic brown adipocytes. The multifaceted aspects of research on UCP make this protein interesting in areas of research as different as studies of ion translocating mechanisms, cellular specificity of gene transcription, control of gene expression by neuromediators, adipocyte differentiation, and the pharmacological treatment of obesity. PMID- 1860615 TI - Superfamily of steroid nuclear receptors: positive and negative regulators of gene expression. AB - The nuclear hormone receptor superfamily is characterized by an impressive functional diversity of its members despite a remarkable overall structural unity. A variety of ligands bind specifically to them and these receptors control gene networks that have profound effects on growth, development, and homeostasis. The ligand-receptor complexes recognize transcriptional enhancer DNA sequences, the hormone response elements, resulting in induction or repression of gene activity. The similarity between all these hormone response enhancer elements, as well as between the receptors themselves, indicates a conserved general strategy for the hormonal control of transcription by steroids. The activated receptors bind to responsive promoters and most likely mediate the assembly of stage- and tissue-specific transcription factor complexes that stimulate or inhibit gene expression. PMID- 1860616 TI - Tumor vaccines. AB - Vaccination against tumor, either as a prophylactic procedure or as a mode of treatment, has been a distant goal of immunologists for many years. Ideally, the less specific therapies such as chemotherapy would be replaced by an anti-tumor immune response in the host that would be present on a continuing basis. However, progress has been hampered by a lack of understanding of the role of viruses in human tumor development and the molecular nature of tumor-associated antigens. Recent developments using the techniques of molecular biology and monoclonal antibody reagents are beginning to remedy this deficiency so that vaccination has become a real possibility for certain human cancers. The natural fluctuations in growth rates of some human tumors, and the observation that tumors can occasionally remain dormant for years, has led to the idea that the host has an intrinsic ability to control tumor growth, and that this ability is a property of the immune system. Attempts to enhance this putative control are being made by treating the host with defined biological modifiers that stimulate cells involved in immunity in vivo, and by seeking and expanding such cells in vitro before reinfusing them into the host. These attempts to harness the immune system to attack tumor cells that have evaded the host's defenses might be considered optimistic, but they will at least tell us a great deal about tumor cell behavior and the ability of the host to influence it. PMID- 1860617 TI - Regulation of eukaryotic phospholipid metabolism. AB - Phospholipids have diverse and critical roles in cellular metabolism and function. Questions about the mechanisms of regulation of phospholipid synthesis are being investigated with a variety of systems and approaches. For example, the yeast Saccharomyces cerevisiae is an organism in which both biochemical and genetic analyses are used. Biochemical approaches have yielded considerable information on the regulatory properties of enzymes of phospholipid biosynthesis. Studies of the activity of purified phosphatidylserine synthase have suggested how that enzyme is influenced by membrane phospholipids in the cell. The enzyme that regulates mammalian phosphatidylcholine biosynthesis, CTP:phosphocholine cytidylyltransferase, is also influenced by phospholipids. In addition, the activity of this enzyme often correlates with its translocation to membranes. The location of such enzymes in the cell is of particular interest in light of the possibility that the enzymatic reactions may be efficiently coupled in vivo. Techniques to render cultured cells permeable to phosphorylated molecules indicated that the enzymes of phosphatidylcholine biosynthesis may exist in an organized compartment so that the precursors of phosphatidylcholine are efficiently channeled through the pathway. To ask how phospholipids are transported in the cell, a combined biochemical and genetic approach has been used. These studies have revealed that the phosphatidylinositol/phosphatidylcholine transfer protein, considered to mediate intracellular phospholipid transfer, is a critical component of the secretory pathway for proteins. These results have allowed formulation of a number of new questions on the regulation of phospholipid metabolism and its relationship to general membrane processes. PMID- 1860618 TI - Pressure and flow-dependent vascular tone. AB - Most small arteries are partially constricted in vivo. After excluding neurogenic, metabolic, and circulating as well as local hormonal influences, a sizeable component of tone persists which is commonly called basal tone. In the absence of such tone, cardiac output would be insufficient to maintain the circulation. This review focuses on the contribution of stretch, induced by changes in transmural pressure, and flow acting through shear forces exerted at the blood vessel wall interface, to basal tone. Evidence concerning the cellular processes that may be activated by these physical forces--the mechanotransducing systems--are discussed. The involvement of the endothelium and the role of change in membrane potential are evaluated and lead to the conclusion that pressure and flow effects do not depend exclusively on the release of endothelial factors nor the activation of voltage-gated Ca2+ channels. Stretch/pressure-induced changes in tone show distinctive pharmacological profiles. They are dependent on extracellular calcium and yet in many instances are only weakly affected by organic Ca(2+)-entry inhibitors. Flow-dependent vascular effects, both constrictor and dilator, are both exquisitely sensitive to changes in extracellular Na+ and appear to be related to its transmembrane gradient. Stretch/pressure cause activation of protein kinase C, an intracellular modulator of Ca(2+)-dependent contractile processes. The existence of separate and distinctive cellular sensing and responding systems to pressure and flow raise the possibility that the smooth muscle tone of the vascular system can be influenced independently by the pressure and rate of flow of the blood. PMID- 1860619 TI - Facts and theories concerning the mechanisms of carcinogenesis. AB - Carcinogenesis can be induced experimentally by exposure to exogenous agents or it can occur spontaneously without intentional or active intervention. Carcinogenesis can be actively induced by chemicals, radiation, infectious biological agents, transgenesis, or selective breeding. In the human and occasionally when testing potential carcinogens in animals, cancer may result from passive exposure to carcinogens encountered in the ambient environment or from changes in the internal milieu of the animal. Many carcinogens alter the structure of DNA resulting in carcinogenesis, but a significant number of carcinogens do not appear to act through this mechanism. When the action of specific carcinogenic agents is considered in relation to the stages of cancer development, initiation, promotion, and progression, the mechanism of the induction of carcinogenesis by DNA-reactive agents that alter genomic structure can be reconciled with those agents that do not act in this manner. As some cells are fortuitously initiated by uncontrolled variables such as irradiation and through changes in normal processes, the stimulation of growth and altered genetic expression by nongenotoxic agents may result indirectly in cancer development. The final stage of carcinogenesis, progression, can occur spontaneously, enhanced by formation and propagation of genetic errors due to increased cellular proliferation associated with the promotion stage. In addition, chemical and viral agents that lack the capacity for initiation and promotion may actively convert cells in the stage of promotion to the stage of progression. Therefore, the diverse mechanisms of action of carcinogenic agents in relation to their effects on specific stages in the natural history of cancer development allow for greater congruence of many of the theories of carcinogenesis. The influence of the roles of nongenotoxic carcinogenic agents and the potential role of progressor agents on the carcinogenesis process allow a more accurate identification of the potential risk that specific carcinogenic agents pose for increasing human cancer. PMID- 1860620 TI - Immunomodulating activity of heparin. AB - Aside from its well-known anticoagulant action, heparin has many other biologic effects. Recent data emphasize the immunomodulatory effects of low dose heparin. The agent alters the traffic of lymphocytes blocking their expression of heparanase, an enzyme that digests the extracellular matrix allowing cell penetration to target tissues. It also has a weak direct immunosuppressive action in vitro and in vivo. Oral administration of heparin may cause immunosuppression, although the effects are weaker than after subcutaneous administration. PMID- 1860621 TI - Lymphocyte interactions with extracellular matrix. AB - To mediate an immune response, lymphocytes must be able to interact with and respond to the surrounding extracellular environment. In addition to cell surface molecules that facilitate adhesion of lymphocytes to other cells, recent studies have demonstrated that lymphocytes interact with glycoproteins and glycosaminoglycans that are major components of the extracellular matrix (ECM). Although many receptors mediating the effects of ECM components on lymphocyte function remain poorly defined, a number of lymphocyte ECM receptors have recently been identified; these include members of the integrin family of adhesion molecules as well as structurally unrelated molecules such as CD44 and CD26. Furthermore, as lymphocytes must be able to move between various microenvironments in vivo, they have proved to be an excellent cell type in which to identify and analyze various modes of regulation of cell-ECM interactions. As with other cell types, the ECM has been shown to have multiple effects on lymphocytes; functional analysis reveals effects of the ECM on lymphocyte migration, recognition/activation, and differentiation. These studies emphasize: 1) the importance of lymphocytes as a model system for identifying and analyzing ECM receptor expression and function, and 2) the multiple roles that the ECM plays in the function of the immune system in vivo. PMID- 1860622 TI - Bicameral grant review: an alternative to conventional peer review. PMID- 1860623 TI - Selecting anesthetic agents for animal research. PMID- 1860624 TI - Status of zinc in nutrition. PMID- 1860625 TI - The cephalic and gastric phases of gastric secretion during H2-antagonist treatment. AB - The antisecretory effects of H2-receptor antagonists are limited by food ingestion. The contributions of the cephalic-vagal and gastrinergic mechanisms to this interaction were examined in two 14-hour randomized, cross-over studies in 24 healthy volunteers. In the first study, either ranitidine or placebo was administered IV by a pH-feedback-controlled infusion pump during fasting, modified sham feeding, or food ingestion. Sham feeding resulted in a well-defined and abrupt interaction with the antisecretory effect of ranitidine (lasting 2-3 hours), after which fasting pH levels were regained. The second study, with the same design, showed that gastrin release occurred during this cephalic-vagal phase but was not attenuated by the additional infusion of the anticholinergic pirenzepine. Following eating, intragastric acidity increased and remained elevated for more than 6 hours. This increase was accompanied by prolonged hypergastrinemia, which was not diminished by pirenzepine. Pirenzepine did, however, enhance the antisecretory effect of ranitidine after both sham feeding and food ingestion. The interaction of food or sham feeding with the antisecretory effect of H2 antagonists is a consistent phenomenon. In both the cephalic-vagal and the gastric phases of secretion, this interaction appears to be partially mediated by a noncholinergic release of gastrin. PMID- 1860626 TI - Effect of intrathoracic pressure on plasma arginine vasopressin levels. AB - Abdominal distention during pneumoperitoneum results in a marked increase in plasma arginine vasopressin levels, which has been ascribed to an increase in intrathoracic pressure. Because of this relationship, tense ascites could contribute to nonosmotic release of antidiuretic hormone, to the development of hyponatremia, and eventually to further ascites formation. The effect of pneumoperitoneum, thoracocentesis, and paracentesis on plasma arginine vasopressin levels was studied in three groups of patients, and the mechanism by which these maneuvers may induce these changes was investigated. Patients with pleural effusion, pneumothorax, or ascites showed a significant increase in plasma arginine vasopressin levels, and thoracocentesis or paracentesis resulted in a decrease in these levels. Plasma vasopressin levels increased significantly during pneumoperitoneum, as did intrathoracic and atrial pressures; the atrial transmural pressure gradient declined. However, no changes in plasma levels of norepinephrine, aldosterone, and renin activity were observed during pneumoperitoneum. Changes in plasma arginine vasopressin levels correlated with the changes in intrathoracic and atrial pressures and transmural pressure gradient. The authors conclude that increased intrathoracic pressure is associated with an increase in plasma arginine vasopressin levels and propose that ascites could be a factor promoting vasopressin release by acting on intrathoracic volume receptors in decompensated cirrhotics. PMID- 1860627 TI - Intestinal obstruction during shigellosis: incidence, clinical features, risk factors, and outcome. AB - To determine the incidence and outcome of intestinal obstruction during shigellosis, the authors assessed 1211 consecutive patients with shigellosis admitted during a 15-month period to a diarrhea treatment center in Dhaka, Bangladesh. Obstruction was identified in 30 (2.5%) patients. Ten (33.3%) of these patients died, compared with 97 (8.2%) of the 1181 patients without obstructions (P less than 0.001; RR = 4.1). In a case-control study, patients with obstructions were compared with 30 control patients with shigellosis but without obstructions. Case and control patients were similar in age (median, 18 months vs. 24 months; NS). Before admission to the hospital, case patients had less often been breast-fed than control patients (33% vs. 85%; P = 0.006) and had more often received antimicrobial agents (53% vs. 13%; P = 0.001). Case patients more often had abdominal tenderness (73% vs. 13%; P less than 0.001), altered consciousness (50% vs. 17%; P = 0.006), and Shigella dysenteriae type 1 infection (73% vs. 27%, P = 0.001) and had a higher median blood leukocyte count (40 x 10(3)/microL vs. 14 x 10(3)/microL; P = 0.007) and serum potassium concentration (5.0 mmol/L vs. 4.3 mmol/L; P = 0.016), and lower median serum sodium (123 mmol/L vs. 131 mmol/L; P = 0.003) and total protein (52 g/L vs. 60 g/L; P = 0.025) concentrations than did control patients. Eight (27%) patients with obstructions developed the hemolytic-uremic syndrome, compared with none of the control patients (P = 0.003). It was concluded that obstruction is an ominous complication of shigellosis and that therapies in addition to provision of antimicrobial agents need to be evaluated. PMID- 1860628 TI - Radioautographic localization of epidermal growth factor receptors in human fetal gut. AB - The present investigation was undertaken to study the localization and accessibility of epidermal growth factor binding sites in the human fetal gut (15 19 weeks of gestation) using light-microscopic and quantitative autoradiography. Exposure of colonic explants to 5 nmol/L 125I-labeled epidermal growth factor for 60 minutes at 22 degrees C revealed extensive accumulation at binding sites in undifferentiated cells of the crypts and at the base of the villus, as well as in the inner circular layer of the muscularis externa bordering the submucosa. Some labeling was also present in the mesenchymal and vascular elements of the lamina propria. Labeling was virtually absent on the brush border at all levels of the epithelium. Quantitative analysis revealed a distinct gradient in grain density along the various compartments of the crypt-villus axis. Epithelial cells in the deep portions of the crypts showed the highest grain density (9.2 grains/microns 2) with values gradually decreasing to 6.5 in upper crypt and 3.9 in lower villus cells. The upper third of the villus showed very little labeling (0.4 grains/microns 2). Cellular distribution of silver grains in lower villous cells revealed a polarization of labeling in the basolateral infranuclear region. Experiments performed at 4 degrees C and at various incubation times showed similar results. Using isolated loops of intact colon and jejunum, segments in which labeled epidermal growth factor was only accessible on the serosal side showed extensive labeling and distribution similar to that found in explanted tissue. On the other hand, labeled epidermal growth factor could not access these same receptor sites when infused into the lumen, either at 22 degrees C or 4 degrees C. These results show that in the human fetal gut (a) the greatest concentration of epidermal growth factor binding sites is found in regions of high proliferative activity and (b) binding sites are absent from the brush border, suggesting that, under normal circumstances, systemic but not luminal epidermal growth factor has free access to its specific receptor. PMID- 1860629 TI - Observations on a proposed measure of genotoxicity in rat gastric mucosa. AB - Current methods for the study of the toxicological effects of antisecretory medications on the gastric mucosa possess disadvantages or limitations. A novel assay has been proposed to assess gastric mucosal genotoxicity in which the proton-pump inhibitor omeprazole has been reported to induce direct damage to cellular DNA, raising questions about the safety of this drug. To define the applicability of this proposed measure of genotoxicity and to examine the effects of omeprazole in this assay, control agents, known carcinogens, and omeprazole in various doses and formulations were administered to rats by gavage, followed by [3H]thymidine labeling of DNA in vivo approximately 14 hours later. The incorporation of the [3H]thymidine label into DNA of gastric mucosal cells liberated by limited pronase digestion was in close agreement with published results for negative and positive controls. Omeprazole, administered in doses ranging from 10 mg/kg to 300 mg/kg, did not increase [3H]thymidine incorporation into cellular DNA in this assay. The gastric carcinogen 1-methyl-2-nitro-1 nitrosoguanidine at 20 and 50 mg/kg increased [3H]thymidine incorporation. Pretreatment in vivo with hydroxyurea before [3H]thymidine labeling to inhibit replicative DNA synthesis suppressed [3H]thymidine incorporation more than 97% in negative controls and MNNG and more than 93% in omeprazole treatments. This indicates that replicative DNA synthesis was almost totally responsible for the [3H]thymidine incorporation and the contribution of unscheduled DNA synthesis to the total [3H]thymidine incorporation is minor. Flow cytometric analysis of the cell cycle of the gastric mucosal cells liberated by the limited pronase digestion indicated significant contamination of the preparation with dividing cells (4% in negative controls and 14% in MNNG-treated positive controls). These findings indicate that the proposed screening assay for genotoxicity in rat gastric mucosa is not a reliable measure of unscheduled DNA synthesis in its present form, and conclusions about genotoxic effects of any drug using this assay as initially proposed appear questionable. PMID- 1860630 TI - Hypertrophic smooth muscle in the partially obstructed opossum esophagus. Excitability and electrophysiological properties. AB - Partial obstruction of the opossum esophagus leads to thickening of the circular muscle, hypertrophy of smooth muscle cells, and diminution of the extracellular space. The pharmacological and electrophysiological properties of this hypertrophied muscle were studied. Carbachol produced phasic and tonic contractions of the circular muscle. The EC50 for tonic contractions was greater for hypertrophied than for normal muscle (21.1 +/- 3.9 mumol/L vs. 4.8 +/- 2.2 mumol/L; P less than 0.05). The resting membrane potential difference of hypertrophied muscle (-50.8 +/- 0.2 mV) was similar to that of normal muscle ( 50.0 +/- 0.2 mV). Electrical stimulation of intrinsic nerves in the normal muscle produced a hyperpolarization followed by a depolarization of smooth muscle membrane potential. Hypertrophied muscle responded either with an attenuated hyperpolarization or no hyperpolarization, both of which were followed by a depolarization. The space constant in the long axes of the hypertrophied circular muscle cells was greater than normal (4.4 +/- 0.2 mm vs. 3.4 +/- 0.1 mm; P less than 0.001). The threshold potential for initiation of action potentials was more negative for hypertrophied (-43.2 +/- 0.4 mV) than for normal circular muscle ( 41.6 +/- 0.2 mV; P less than 0.005). These data indicate that alterations in neuromuscular function accompany the hypertrophy of esophageal smooth muscle. PMID- 1860631 TI - Trichinella spiralis infection alters small bowel motor activity in the fed state. AB - The effect of Trichinella spiralis infection on small intestinal transit and motor activity in the fed state during the intestinal phase of infection was studied. Contractions were recorded by strain gauge transducers, and mean transit time was measured by marker dilution technique. The mean amplitude and area of individual phasic contractions decreased, but no change occurred in their mean duration during trichinosis. The total amplitude and area of phasic contractions also decreased; this was caused by a decrease in the frequency of contractions as well as a decrease in the mean parameters. The reduction in the total duration was entirely caused by the decrease in frequency. The reduction in the total parameters of all contractions was the result of a reduction in the same parameters for both propagating and nonpropagating contractions. However, the decrease in the parameters of propagating contractions was much greater. Also, there was a decrease in the distance of propagation of phasic contractions. The transit time as a result of phasic contractions increased during T. spiralis infection. Additionally, T. spiralis infection induced giant migrating contractions in the fed state that were never observed during control. Chyme was propelled very rapidly and effectively by giant migrating contractions. The findings of the present study suggest that during diarrhea induced by T. spiralis infection, the phasic contractions may act to decrease transit and, hence, allow more contact time for absorption of water and nutrients. However, this response may be counter-balanced by giant migrating contractions that rapidly propel chyme into the colon and compound the diarrhea associated with T. spiralis infection. PMID- 1860632 TI - Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor gamma/delta in inflammatory bowel disease. AB - Phenotypic characterization and distribution of gamma/delta T lymphocytes in the intestinal mucosa were investigated in ulcerative colitis and Crohn's disease by immunohistochemistry. The ratio of delta(+) cells to CD3(+) cells in the intraepithelial space of colon was decreased in Crohn's disease (13%) and strikingly decreased in ulcerative colitis (8%) compared with the control (36%). Delta(+) cells in the lamina propria were also decreased, particularly in the distal ileum of Crohn's disease (4%), compared with the control (15%). On the contrary, the cells gathered at the severe inflammatory sites with other inflammatory cells, including beta(+) cells, and were densely distributed in the T-cell zone around lymphoid follicles. Phenotypic characterization showed that delta(+) lamina proprial lymphocytes of colon were mainly CD4(-)CD8(-) in the control (80%) and Crohn's disease (59%). However, in ulcerative colitis, CD4( )CD8(-) delta(+) lymphocytes were rarely found (3%). This reflects the difference of immunologic background between the two diseases. Immunoelectron microscopically, these cells in inflammatory bowel disease were rich with vesicular structures in cytoplasms, whereas those in the control group contained electron-opaque granules. The decrease and the morphological change may be closely related to the weakness of mucosal defense. PMID- 1860633 TI - Acute abdomen as the first presentation of pseudomembranous colitis. AB - Acute abdomen was the presenting manifestation of pseudomembranous colitis in six men who had previously been treated with antibiotics and presented with abdominal distention, pain, fever, and leukocytosis with absent or mild diarrhea. Plain abdominal radiographs revealed megacolon in two, combined small and large bowel dilation in three, with one of them showing volvuluslike pattern, and isolated small bowel ileus in one. Emergency colonoscopy was performed successfully in all patients and revealed pseudomembranes in five and nonspecific colitis in one. All patients had positive latex test results for Clostridium difficile, and two tested positive for cytotoxicity. All patients were treated with IV metronidazole, resulting in resolution of symptoms and abdominal findings. In addition, two patients underwent colonoscopic decompression with improvement. Endoscopically, complete resolution of the pseudomembranes occurred at 4 weeks in all cases. No patient had a recurrence. It is concluded that (a) pseudomembranous colitis may present as abdominal distention mimicking small bowel ileus. Ogilvie's syndrome, volvulus, or ischemia; (b) in such cases, emergency colonoscopy is safe and useful for diagnosis and therapeutic decompression and may obviate the need for surgery; and (c) treatment with IV metronidazole is effective. Colitis due to C. difficile should be considered in the differential diagnosis of acute abdomen in patients previously treated with antibiotics. PMID- 1860634 TI - Mechanism for the gastrokinetic action of domperidone. In vitro studies in guinea pigs. AB - To test the hypothesis that domperidone stimulates gastric muscle contraction by antagonizing the inhibitory effects of dopamine on postsynaptic cholinergic neurons in the myenteric plexus, the effects of dopamine on circular muscle from the body of the guinea pig stomach were examined. Dopamine inhibited circular muscle contraction evoked by electric field stimulation in a dose-related manner. The threshold dose was 10(-6) mol/L and half-maximal inhibition occurred at 10( 5) mol/L. Preincubation of muscle contraction with atropine or tetrodotoxin abolished the contractile response to electric field stimulation, indicating mediation via a cholinergic pathway. The adrenergic antagonists phentolamine and propranolol and the DA1 antagonist SCH 23390 were ineffective in antagonizing the action of dopamine. In contrast, the DA2 antagonist domperidone blocked the inhibitory effect of dopamine on electric field stimulation-mediated contractions. Schild analysis showed a Ki of 3 x 10(-8) mol/L and a slope of unity. In addition, it was shown that dopamine inhibited veratridine-evoked release of [3H]acetylcholine from the gastric myenteric plexus in a dose-related manner (median effective dose, 5.2 x 10(-5) mol/L). Tetrodotoxin abolished [3H]acetylcholine release evoked by veratridine, but hexamethonium had no effect. Domperidone, but not SCH 23390, antagonized the inhibitory action of dopamine. Pretreatment with pertussis toxin blocked the action of dopamine to inhibit evoked release of [3H]acetylcholine. These observations indicate that dopamine inhibits gastric muscle contraction evoked by electric field stimulation by inhibiting cholinergic transmission. This is mediated by DA2 receptors located on the postganglionic cholinergic neurons, and the pathway involves a pertussis toxin-sensitive G protein. The DA2-receptor antagonist domperidone antagonizes the inhibitory effect of dopamine, resulting in stimulation of gastric muscle contraction. This provides a mechanism for the gastrokinetic effect of domperidone. PMID- 1860635 TI - Cancer incidence following subtotal gastrectomy. AB - Hawaiian Japanese men (n = 432) who had undergone subtotal gastrectomy for peptic ulcers before 1971-1975 were followed up for detection of cancer development. They showed a significant increase in colon cancer risk (P = 0.008) and lung cancer risk (P = 0.002) compared with 6161 nongastrectomized men. The association with lung cancer persisted after adjustment for cigarette use (P = 0.03). Alcohol consumption was associated with colonic cancer in this cohort, and gastrectomized men consumed more alcohol than nongastrectomized men; however, the association of gastrectomy with colon cancer persisted after adjustment for alcohol use (P = 0.02). Gastrectomized men were lighter and had lower serum lipid levels than controls, suggesting that undernutrition might favor the development of some cancers. The type of gastroenteric anastomosis did not influence the cancer risk level in the colon or lung. PMID- 1860637 TI - Classic and vigorous achalasia: a comparison of manometric, radiographic, and clinical findings. AB - Compared with classic achalasia, vigorous achalasia has been defined as achalasia with relatively high esophageal contraction amplitudes, often with minimal esophageal dilation and prominent tertiary contractions on radiographs, and with the presence of chest pain. However, no study using current manometric techniques has compared manometric, radiographic, and clinical findings in vigorous and classic achalasia or questioned the usefulness of making this distinction. Fifty four cases involving patients with achalasia whose radiographic and manometric studies were performed within 6 months of each other were available for review. Patients with vigorous achalasia (n = 17), defined by amplitude greater than or equal to 37 mm Hg, and patients with classic achalasia (n = 37), defined as amplitude less than 37 mm Hg, had substantial overlap in radiographic parameters of esophageal dilation, tortuosity, and tertiary contractions. Manometric properties of repetitive waves and lower esophageal sphincter pressure and clinical aspects of chest pain, dysphagia, heartburn, and satisfactory responses to pneumatic dilation were similar in both forms of achalasia. A separate analysis of patients with mean contraction amplitude greater than 60 mm Hg revealed similar findings. It is concluded that use of amplitude as a criterion for classifying achalasia is arbitrary and of dubious value. PMID- 1860636 TI - Antitumor effect of synthetic derivatives of lipid A in an experimental model of colon cancer in the rat. AB - Colon carcinoma is one of the most frequent causes of cancer death in industrialized countries. The patients generally die of the metastases. In a colon cancer rat model, the authors have shown that lipopolysaccharides from Escherichia coli induced the regression of carcinomatosis and cured 20%-30% of the rats. Some synthetic derivatives of lipid A, which are less toxic than lipopolysaccharides, were injected 14 days after the tumor cells. They induced the complete regression of peritoneal carcinomatosis consisting of numerous nodules measuring 1-5 mm in 20%-30% of rats. Only compounds with three or more hydroxymyristic acid residues were effective. In vivo effects were correlated with the capacity to induce the production of interleukin 1 and tumor necrosis factor but not with the capacity to induce macrophage-mediated cytolysis. It is therefore possible to synthesize weakly toxic derivatives of lipopolysaccharides retaining their antitumoral property in vivo. PMID- 1860638 TI - Apolipoprotein synthesis in normal and abetalipoproteinemic intestinal mucosa. AB - The genetic disease abetalipoproteinemia is characterized by a total absence of apolipoprotein B-containing lipoproteins from plasma. A presumed synthetic defect in apolipoprotein B synthesis was thought to be responsible for this disorder. The present study quantitates apoprotein B synthesis and apolipoprotein B messenger RNA levels in duodenal mucosa from normal patients and four patients with abetalipoproteinemia. After in vitro [3H]leucine incorporation, small intestinal biopsy specimens from three of four patients with abetalipoproteinemia synthesized immunoprecipitable apolipoprotein B of identical mobility (on sodium dodecyl sulfate gel electrophoresis) to normal apolipoprotein B. In abetalipoproteinemia, the apolipoprotein B content of intestinal mucosa by radioimmunoassay was 15% of normal mucosal values, whereas apolipoprotein B messenger RNA quantitation showed 3-20-fold increased levels compared with normal mucosa. In one patient, smaller-molecular-weight fragments of apolipoprotein B were immunoprecipitated from duodenal biopsy specimens. The synthesis rates and messenger RNA levels of two other chylomicron apoproteins (apolipoprotein A-I and apolipoprotein A-IV) were found to be reduced by 50%. These results show the synthesis of immunologically recognizable apolipoprotein B48 in abetalipoproteinemia. The significance of mucosal apolipoprotein B content in abetalipoproteinemia is discussed in terms of factors controlling apolipoprotein B synthesis in normal mucosa and in abetalipoproteinemia. PMID- 1860639 TI - Nonsalicylate nonsteroidal antiinflammatory drugs augment prestimulated acid secretion in rabbit parietal cells. Investigation of the mechanisms of action. AB - The effects of nonsalicylate nonsteroidal antiinflammatory drugs on acid secretion were studied in isolated rabbit parietal cells. Indomethacin, naproxen, and carprofen (10(-6)-10(-4) mol/L) potentiated histamine-, forskolin-, 3 isobutyl-1-methylxanthine-, and dibutyryl cyclic adenosine monophosphate stimulated acid secretion without affecting basal acid secretion. This augmentation of secretagogue-stimulated acid secretion was dependent on extracellular calcium because potentiation was abolished by calcium depletion of the medium or in the presence of the calcium antagonist lanthanum chloride. Potentiation was independent of the H2 and muscarinic receptors and did not appear to involve guanine nucleotide regulatory proteins. Proton pump activity was unaffected by indomethacin. Furthermore, nonsteroidal antiinflammatory drugs increased calcium efflux through the plasma membrane, as measured by calcium 45, and decreased endogenous prostaglandin E2 content. Exogenous dimethyl prostaglandin E2 inhibited the potentiating effect of these drugs on histamine stimulated but apparently not on dibutyryl cyclic adenosine monophosphate stimulated acid secretion. The data indicate that nonsalicylate nonsteroidal antiinflammatory drugs interacted at a postreceptor site between adenylate cyclase and the proton pump. The potentiating effects of these drugs were regulated by calcium and possibly modulated by prostanoids. PMID- 1860640 TI - Acalculous biliary pain: cholecystectomy alleviates symptoms in patients with abnormal cholescintigraphy. AB - A 45-minute infusion of an octapeptide of cholecystokinin (Kinevac; Squibb Diagnostics, New Brunswick, NJ) was used to measure the gallbladder ejection fraction during cholescintigraphy in 40 normal volunteers. Cholecystokinin cholescintigraphy was shown to be a reproducible test. The maximum mean gallbladder ejection fraction occurred 15 minutes after cholecystokinin infusion and was 74.5% +/- 1.9% (mean +/- SEM). A gallbladder ejection fraction greater than 40% (mean -3SD) was arbitrarily defined to be normal. The gallbladder ejection fraction test was then used to identify patients with acalculous biliary symptoms who may respond to cholecystectomy. A total of 103 patients was tested; 21 had abnormal gallbladder ejection fractions and were randomized into two groups, cholecystectomy or no operation. These patients were followed up symptomatically at 3-month intervals for 13-54 months (mean, 34 months). Of the 11 patients who underwent cholecystectomy, 10 (91%) lost their symptoms and 1 improved. Of the 10 patients in the group that did not undergo surgery, all continued to be symptomatic, 2 of whom requested cholecystectomy after 13 and 24 months, respectively. Of the 13 gallbladders obtained from surgery, 12 showed evidence of chronic cholecystitis, muscle hypertrophy, and/or narrowed cystic duct. A normal gallbladder ejection fraction was recorded in 82 patients, and further treatment was left to the discretion of their referring clinician. On follow-up, 50 patients were asymptomatic and 10 were symptomatic without specific treatment of the biliary tract; 14 underwent cholecystectomy, 8 of whom were asymptomatic. Pathological abnormalities were recorded in 6 of the removed gallbladders. It is concluded that the gallbladder ejection fraction obtained after a 45-minute infusion of cholecystokinin during cholescintigraphy is a reproducible measure of gallbladder emptying, and that cholecystectomy alleviates the biliary-type pain of patients with a reduced gallbladder ejection fraction. PMID- 1860641 TI - Noninvasive measurement of liver regeneration with positron emission tomography and [2-11C]thymidine. AB - The feasibility of liver regeneration determination with [2-11C]thymidine and positron emission tomography was investigated in partially hepatectomized rats. Serial tomographic scans were performed over a 120-minute period after injection of [2-11C]thymidine together with tritium-labeled thymidine. Within 10 minutes after injection, positron emission tomography scans showed a twofold higher hepatic uptake in regenerating than in nonregenerating livers. Time-activity curves over the liver area indicated that the maximal uptake was followed by a faster decrease of 11C radioactivity in controls than in regenerating animals, so that total 11C activity remaining in the liver at 120 minutes accounted for 68% of maximum in regenerating and only 38% in controls. Tissue distribution studies performed at 120 minutes showed that total 11C radioactivity, expressed in percent injected dose per gram, was six times higher in regenerating livers than in controls (0.62% +/- 0.07% in regenerating livers and 0.10% +/- 0.03% in nonregenerating livers; P less than 0.001) and correlated with 3H radioactivity measured in the nuclear fraction (r = 0.92; P less than 0.001). When the hepatic uptake was expressed in percent of dose per organ, the difference between both groups increased (2.31% +/- 0.23% in regenerating livers and 0.29% +/- 0.02% in nonregenerating livers; P less than 0.001) because of higher weight of regenerating livers than of nonregenerating livers (3.83 +/- 0.11 g in regenerating livers and 2.96 +/- 0.16 g in nonregenerating livers; P less than 0.001). In other organs examined, no difference in 11C radioactivity was found between the two groups of rats. These results indicated the potential usefulness of [2-11C]thymidine and positron emission tomography for noninvasive measurement of liver regeneration. PMID- 1860642 TI - The effects of chronic endoscopic variceal sclerotherapy on portal pressure in cirrhotics. AB - The effect of obliterating esophageal varices by endoscopic sclerotherapy on portal pressure was prospectively studied in 11 cirrhotic patients with variceal hemorrhage. Portal venous pressure gradient, determined as the difference between transhepatic portal and hepatic vein pressure, increased by a mean of 31.1% +/- 14.5% in 8 (73%) and decreased by a mean of 30.1% +/- 11.7% in 3 (27%) patients, with no statistically significant change overall (P = 0.1). These changes in portal venous pressure gradient occurred despite an improvement in the laboratory and clinical parameters of hepatic function. Deep abdominal sonography with color flow imaging at variceal obliteration showed patent paraumbilical veins in 6 (55%) patients, 3 of whom had decreases in portal venous pressure gradient (29%, 19%, 42.5%) at variceal obliteration. In 5 (45%) patients without patent paraumbilical veins, a statistically significant increase in portal venous pressure gradient between initial endoscopic variceal sclerotherapy and variceal obliteration was noted (P = 0.008). Rebleeding (single episode in all 4 patients, before obliteration in 3 patients) occurred in those with an increase in portal venous pressure gradient; all patients with portal venous pressure gradient decreases were nonbleeders. No correlation between changes in portal venous pressure gradient and time to variceal obliteration, number of sclerotherapy treatments, or rebleeding episodes was observed. Thus, an increase in portal venous pressure gradient was noted in the majority of patients at variceal obliteration. Although the portal venous pressure gradient decrease may be explained by a patent paraumbilical vein, the mechanism of portal venous pressure gradient increase is not clear. It is speculated that this portal venous pressure gradient increase may be caused by an increase in collateral resistance or flow or a combination of both, resulting from obliteration of esophageal varices by endoscopic sclerotherapy. PMID- 1860643 TI - Chronic dietary iron overload in rats results in impaired calcium sequestration by hepatic mitochondria and microsomes [corrected]. AB - The purpose of these experiments was to determine whether chronic dietary iron overload causes impairment of hepatic mitochondrial and/or microsomal calcium sequestration. Experimental iron overload was produced by feeding three groups of rats a chow diet supplemented with 3.0% (wt/wt) carbonyl iron for up to 8 weeks achieving graded increases in hepatic iron concentrations ranging from 1360 to 3170 micrograms/g. At low levels of iron overload, there were no changes in mitochondrial oxidative metabolism or calcium sequestration, whereas at moderate and high degrees of iron loading, both of these parameters were significantly reduced. In contrast, there were significant decreases in microsomal cytochrome P450 levels and microsomal calcium sequestration at all three levels of iron loading. These abnormalities occurred at hepatic iron concentrations at which the authors have previously found evidence of hepatic organelle lipid peroxidation. These alterations in organelle calcium sequestration may impair intracellular calcium homeostasis in the liver and contribute to subsequent cellular injury. PMID- 1860644 TI - Inhibition of prostaglandin synthesis fails to prevent gallbladder mucin hypersecretion in the cholesterol-fed prairie dog. AB - Gallstone formation in the cholesterol-fed prairie dog is preceded by an increase in mucin secretion by the gallbladder epithelium, and mucin hypersecretion is believed to promote cholesterol gallstone formation by accelerating the nucleation of cholesterol monohydrate crystals. Some studies have suggested that gallbladder mucin hypersecretion is mediated by increases in gallbladder prostaglandin synthesis, but other observations are difficult to reconcile with this view. An organ culture technique was used to measure mucin secretion in normal prairie dog gallbladder in response to exogenous prostaglandins and agents that increased or decreased endogenous prostaglandin production. Incubation with indomethacin produced a concentration-dependent inhibition of endogenous prostaglandin synthesis with virtually complete inhibition at 10(-5) mol/L indomethacin. However, indomethacin had no effect on gallbladder mucin secretion at concentrations as high as 10(-5) mol/L, and significant inhibition of mucin secretion was only found at 10(-4) mol/L indomethacin, a concentration that also produced a significant increase in lactate dehydrogenase release from cultured explants. Incubation of gallbladder explants with the calcium ionophore A23187 significantly stimulated endogenous prostaglandin synthesis in a concentration dependent manner, increasing synthesis of prostaglandins E and F to as much as 278% +/- 20% and 335% +/- 21% of basal values, respectively; however, the same concentrations of A23187 did not stimulate mucin secretion. Incubation of gallbladder explants in the presence of exogenous prostaglandin E2 or prostaglandin F2a in concentrations as high as 10(-6) mol/L also did not stimulate mucin secretion. Prairie dogs fed a lithogenic 1.2% cholesterol diet showed a significant increase in gallbladder mucin secretion after 1 week (117.5 +/- 10.2% of control, P less than 0.05), and 4 of 5 had formed cholesterol monohydrate crystals after 3 weeks. Long-term treatment with indomethacin, 1.2 mg.kg-1.day-1, failed to inhibit gallbladder mucin hypersecretion (129.2 +/- 10.7% of control after 1 week) or cholesterol monohydrate crystal formation (3/5) in cholesterol-fed prairie dogs. Furthermore, incubation of explants with 10(-5) mol/L indomethacin failed to prevent in vitro mucin hypersecretion in cholesterol fed animals. These findings suggest that prostaglandins do not regulate gallbladder mucin secretion in the prairie dog, and it is unlikely that increases in gallbladder prostaglandin synthesis are responsible for mediating gallbladder mucin hypersecretion during cholelithiasis in the prairie dog. PMID- 1860645 TI - Microanalysis of bile acid composition in intrahepatic calculi and its etiological significance. AB - Brown pigment stones in the intrahepatic bile ducts were compared with those found in the extrahepatic bile ducts with special reference to the bile acids modified by bacterial intervention, that is, unconjugated, glucuronidated, secondary, and ketonic bile acid fractions. The former showed significantly lower amounts of total bile acids (P less than 0.01) and lower proportions of unconjugated bile acid fraction (P less than 0.01), secondary bile acid fraction (P less than 0.05), and ketonic bile acid fraction (P less than 0.05) to total bile acids than the latter. The discriminant analysis using these bile acid parameters led to complete separation between intrahepatic and extrahepatic stones in the case of brown pigment stones. In contrast, cholesterol stones in the intrahepatic bile ducts showed the bile acid composition close to those found in the extrahepatic ducts and gallbladder. The above data show that the bacterial infection plays a less important role in the formation and ensuing growth of most intrahepatic brown pigment stones than in extrahepatic stones, and that factors other than or in addition to bacterial infection are involved. PMID- 1860646 TI - Interferon-induced chronic active hepatitis? AB - A 54-year-old man with chronic B hepatitis was treated with interferon alfa. Despite resolution of the hepatitis B viral infection, he experienced severe jaundice, ascites, and encephalopathy. Further work-up showed hyperglobulinemia, chiefly immunoglobulin G, and positive smooth muscle and anti-nuclear antibodies. Because of these "autoimmune" features, the patient was treated with prednisone. One month later, a significant clinical and biochemical improvement was observed. A possible autoimmune mechanism induced by interferon alfa is proposed as the cause for the perpetuation of the necroinflammatory activity. PMID- 1860647 TI - A reappraisal of the magnitude and implications of the intestinal unstirred layer. AB - Until recently, a variety of studies had suggested that luminal stirring in the jejunum is relatively poor, with unstirred layers of about 600 microns reported for humans and 300-900 microns for animals. Unstirred layers of this magnitude would markedly retard the absorption of all solutes, and diffusion through this layer would be the rate-limiting step in the uptake of all rapidly absorbed compounds. As a result, luminal stirring, rather than epithelial transport, would be the major variable influencing absorption rate. However, recent studies in dogs and humans have shown that the unstirred layer has a maximal apparent thickness of only about 40 microns. This layer is far thinner than what can be achieved in vitro with vigorous stirring with a magnetic bar, suggesting that some unique stirring mechanism, perhaps villous contractions, is responsible for this extraordinarily efficient mixing. A 40-microns unstirred layer would produce only about 1/15 the resistance of the previously reported 600 microns value; with this thinner layer, alterations in either luminal stirring or epithelial function could readily influence the absorption rate of rapidly transported compounds. PMID- 1860648 TI - Hypoproteinemia, anemia, and failure to thrive in an infant. PMID- 1860649 TI - Lessons from experimental cholelithiasis: gallbladder and mucosa, nonsteroidal antiinflammatory drugs, and gallstones. PMID- 1860650 TI - One more reason for weight loss in patients with AIDS. PMID- 1860651 TI - Acute and chronic giant cell hepatitis: a paramyxovirus infection? PMID- 1860652 TI - Peliosis hepatis: old disease, new cause. PMID- 1860653 TI - A biopsychosocial model for functional dyspepsia. PMID- 1860654 TI - Free radical scavengers and inflammatory bowel disease. PMID- 1860655 TI - Prevalence of columnar-lined (Barrett's) esophagus. PMID- 1860656 TI - Asthmatics' gastroesophageal reflux with or without bronchodilator therapy. PMID- 1860657 TI - [Estrogen substitution therapy in climacteric: should progesterone be omitted in hysterectomized women?]. AB - The replacement therapy in postmenopausal women is seen to be for transformation of the oestrogen-stimulated endometrium only, which does not apply to hysterectomised women. Because of the influence of estrane on lipids, one often advises against a replacement therapy with progestogens in hysterectomised women. With increasing knowledge of encountered extragenital functions of sexual steroids, the latter is questionable, if natural progesterone is given, which is (said to be) lipid-neutral, performing the function of the progestogens, which is quite more than reproduction only, more efficiently than estrane or gonane. Due to the competitive blocking of aldosterone the effect of progesterone is sodium diuretic and diuretic, being as important as the therapy of climacteric complaints, as well as the consequence, which is the result of the physiological connection between progesterone and encephalics. Moreover, the effect of the progestogens is to tonicise the vascular system and is linked to a number of intestinal hormones in order to adjust their function. Therefore, progesterone seems to perform a great variety of extragenital functions. Menopausal women should not be deprived of the benefits of these functions within the framework of a replacement therapy. PMID- 1860658 TI - [Diagnostic problems in local recurrence after breast saving therapy of breast cancer]. AB - From 1970 to 1987, 331 breast cancer patients of the Department of Gynaecology of the University of Erlangen were treated by conservative breast surgery. Adjuvant radiotherapy of the remaining breast was applied to only one-third of the patients. 30 patients (9.8%) had a local recurrence. This study analyses the 21 patients with local recurrence after breast conserving therapy, treated afterwards again in our hospital. 60% of the recurrences occurred within 2 years after the primary treatment. In 18 cases, the recurrences were located in the vicinity of the segmental resection area, in 3 cases the recurrences were diagnosed as new second primaries in the ipsilateral breast. 19 of the 21 recurrences were diagnosed by palpation, 2 cases were detected by mammography examination only. The palpable recurrences could only be shown in the mammography in 14 cases. We conclude, that for patients with breast conserving therapy, a mammographic examination need not be increased in frequency, but a quarterly examination by palpation should be extended over more than 2 years. PMID- 1860659 TI - [Recurrence of stage I endometrial cancer: effect of prognostic factors on therapeutic results]. AB - Endometrial carcinoma is the most common gynaecological invasive cancer. Since its incidence is increasing, more patients will develop recurrent disease. In an attempt to identify possible prognostic factors associated with survival, we reviewed the results of 45 patients treated in our department for recurrent clinical stage I endometrial carcinoma. All patients received primary therapy consisting of surgical resection. 16 patients developed recurrent disease after initial operative treatment and adjuvant radiotherapy. The minimum follow-up of 3 years was available in 43 patients and the actual 3-year survival rate was estimated 42% (median 16 months). Significant prognostic factors were recurrence site--vagina, 51% (17/33 pts) vs extravaginal, 20% (2/10 pts) (p = 0.01), and histological cell type--non-papillary carcinoma, 50% (17/34 pts) vs papillary adenocarcinoma, 22% (2/9 pts) (p = 0.02). Late recurrences have been reported to carry a better prognosis, than those that recur early. In the present study, time of onset did not appear to be a significant factor--recurrence occurs within 24 months, 36% (9/25 pts) vs recurrence appearing after 2 years, 55% (10/18 pts). We suggest, that systemic therapy should be prospectively evaluated in high-risk patients. Selected patients with recurrent disease--cases of non-papillary histological cell type and vaginal recurrence--can be cured by radiotherapy. PMID- 1860660 TI - [Doppler ultrasonography--perinatal data in cases with end-diastolic block and reverse flow]. AB - In 50 cases with an end-diastolic zero flow or reverse flow all antenatal and perinatal abnormalities have been recorded. The fetal outcome was registered. The percentage of highly dystrophic newborns (percentile less than 5) was 88%. The perinatal mortality counted up to 16% and the percentage of congenital malformations (including chromosomal anomalies) was 12%. A reverse flow was registered in 4 cases. The perinatal mortality of those cases with reverse flow was 100%. In approx. one-quarter of those pregnancies and in 50% of the perinatally deceased newborns, there were no pathological or suspicious changes in the antepartal and/or subpartal CTG-recordings. The Duplex sonographical diagnosis of an end-diastolic zero flow/reverse flow, has a highly positive predictive value, whereas its sensitivity is low. It can be regarded as a very helpful parameter in clinical diagnosis, particularly as it is independent of borderline values. The correct choice of the high-pass wall filter (50-100 Hz) is important. PMID- 1860661 TI - [Stillbirth--an analysis of 354 cases 1966-88]. AB - A study was conducted on the collection of stillbirths occurring during the last 23 years in the Gynaecological Hospital in Bamberg. The data were taken from the birth reports and the recorded course of each pregnancy. The results of the first 22 years were divided into 2 groups, the first 11 years and the subsequent 11 years, to enable better judgement of trend changes. A total number of 354 children died antepartum or subpartum, the larger group (249) being that in the first 11 years of the observation period. The number of stillborn babies decreased from 40 per year (15%) to 3 per year (1.1%) in the first period. In the collective group the regular participation in prenatal visits increased from 24% to 56%. The percentage of single mothers (9%) remained constant. The number of foreign mothers, who are non-German citizens rose from 2% to 8%. As expected, the rate of stillbirths for twins was almost 4 times higher (5.3%) than for the single pregnancies. The percentage of multiparous women decreased from 66% to 48%. The number of stillbirths, preceded by a miscarriage and abortion in the patient's clinical history, remained constant at 17%. The age distribution of the mothers was almost the same for both observation periods. The usual age of the pregnancy at the time of the stillbirth shifted from the 39th-42nd week to the 35th-38th week. The main complication for the entire group was pre-eclampsia, at the rate of 30%. Amnion infection syndrome (4%) and diabetes mellitus (2%) were rare. The primary cause of foetal death was related to placental dysfunction (40%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860662 TI - [Peritoneal deciduosis: cause for mechanical ileus in pregnancy]. AB - Decidual transformation of the peritoneum is a frequent occurrence during pregnancy. Incidence and pathogenesis are vague. Complications like bleeding, suspicion of cancer and adhesions are rare. We present a case of mechanical ileus, followed by acute prerenal failure of the kidney caused by decidual transformation of the peritoneum. PMID- 1860663 TI - [Acute initial manifestation of systemic lupus erythematosus in the puerperium]. AB - Lupus erythematosus first diagnosed in pregnancy or puerperium is a problem both for the obstetrician and for the internist. We report on a case of lupus manifestation with signs and symptoms similar to sepsis diagnosed in the puerperium. PMID- 1860664 TI - [Manifestations of ruptured liver hematoma as a severe complication of HELLP syndrome]. AB - A case of a ruptured haematoma of the liver with intra-abdominal bleeding is reported. The 26-year old primigravida was admitted in the 31st week of gestation because of a HELLP syndrome. She presented additional symptoms, that are considered typical for a HELLP syndrome, complicated by a ruptured haematoma of the liver: severe right upper-quadrant pain, decrease of haemoglobin content, enlarged liver with structural irregularities and free fluid in the abdominal cavity as examined by sonography. During Caesarean section, a subcapsular haematoma of the liver, combined with a 5 cm laceration of the organ surface, was found. The defect was closed with collagen gauze and clotted with fibrin. Additionally the liver was compressed by abdominal compression towels, which were removed 2 days later. The postoperative development was, in the main, complication free. PMID- 1860665 TI - [Unusual, supernatural presentations of birth in mythology and legends]. AB - Although a multitude of differently motivated explanations have been brought forth in connection with legendary and pictorial representations of unusual- mostly extragenital-birth, an attempt is made to demonstrate certain common features by means of numerous examples. A hero or a god was not supposed to be born naturally ("naturally" being synonymous with "unclean", "contaminated"); his birth had to take place in an extravagant manner and was thus an attribute of immortality. Proof of this, for example, is the creation of Adam and Eve in Genesis. Special attention is given to the biphasic character of creation of life: 1. the lifeless figure, and 2. the act of animation, of coming to life. A large variety of comparisons from legends, myths and tales are exemplified by means of illustrations, such as e.g. the birth of the Buddha, Mithras, Athena, Dionysos, Adonis etc. PMID- 1860666 TI - [Critical comments on the contribution by B. Warkentin: "Late gestosis as a compensation mechanisms in intrauterine growth retardation and the effect of blood pressure lowering therapy"]. PMID- 1860667 TI - ["Is consecutive curettage of the corpus uteri indicated in every case of conization"?]. PMID- 1860668 TI - Race differences in self-perception and locus of control during adolescence and early adulthood: methodological implications. AB - Data from a longitudinal sample of 14,721 White (7,193 men, 7,528 women) and 5,197 Black (2,400 men, 2,797 women) American high school students tested first between ages 16 and 19 and then in two follow-ups 4 and 6 years later were examined to determine Black-White and male-female differences in self-esteem and causal orientations. On general self-esteem scores, Blacks rated themselves more positively than Whites. Blacks also rated themselves more positively on specific self-beliefs (e.g., social attractiveness), although the magnitude of differences in such cases was quite small. On control measures, Blacks perceived greater external control pertaining to both cultural events and personal efficacy, although they had slightly greater expectations about future academic success. Results concerning the general and personal self-efficacy of Blacks were somewhat inconsistent with earlier reports (Coleman et al., 1966; Osborne & LeGette, 1982). Women tended to show less self-efficacy than men, but there were no interactions of race and sex. Even in the presence of significant effects for race and sex, mean differences tended to be relatively small. PMID- 1860669 TI - Life-span attachment: relations between attachment and socioemotional functioning in adult women. AB - Relations between the quality of adult women's attachments, their well-being, and their strategies for coping with stress were explored. In Study 1, we examined elderly women's (65-87 years of age) attachments to their adult children. No main effect differences were found, but extreme score analyses revealed that women with insecure attachments more often evidenced relatively extreme negative scores on measures of social, psychological, and physical well-being and reported using more strategies in coping with stress. In Study 2, we examined the quality of attachments of young adult (mean age = 20 years) and mature women (mean age = 38 years), respectively, to their closest attachment figure. Again, few main effects were found but extreme score analyses revealed that insecurely attached women more often scored in the clinical range on depression and reported more responses in coping with stress. Further friends independently reported more anxiety among insecurely attached women. PMID- 1860670 TI - Aggression in African-American boys: a discriminant analysis. AB - The main purposes of this study were to determine whether familial variables found to be related to the development of aggressive behavior in Caucasian boys may also be related to similar aggressive patterns in inner-city African-American boys and to assess the relative importance of these variables for classifying the subject population into aggressive and nonaggressive groups. Discriminant analyses were performed using 83 African-American boys, with a mean age of 13.9 years, who were classified as institutionalized aggressive, noninstitutionalized aggressive, and noninstitutionalized nonaggressive subjects. Although the same father and mother variables were used in the analyses, the father variables were not related to group membership. Furthermore, the results showed that both groups of aggressive boys reported more aggression within as well as outside their family home settings than their nonaggressive counterparts. Socioeconomic-related factors such as employment status of parent(s), size of family, and number of parents in the household were not useful predictors of aggressive and nonaggressive group membership. PMID- 1860671 TI - Deletions in plasmid pBR322: replication slippage involving leading and lagging strands. PMID- 1860672 TI - [Tubo-peritoneal factor. Endometriosis]. AB - Fifty cases of tuboperitoneal endometriosis with sterility, are reviewed. Laparoscopy was done in all the patients to confirm disease, and its severity was classified to AFS; 18 cases were of minimal endometriosis; 8 slight; 12 moderate; and 12 severe. The endometriotic profile in our environment is described and compared with which has been described in progresist countries; 32% of pregnancy at term, was obtained. The possible mechanisms producing sterility, are mentioned. PMID- 1860673 TI - [Culture of amniotic fluid cells]. PMID- 1860674 TI - [Diagnostic and therapeutic management and results of the neuroendocrine factor in sterility]. AB - One hundred and fifty patients with neuroendocrine alteration, mainly anovulation, proven by basal temperature and endometrial biopsy, were studied. Clinical history and basic examinations for sterility, were carried out. The neuroendocrine factor, alone or associated, was found in 35% of the patients studied for sterility. Primary sterility was 59.3% of the cases. The vagino cervico-spermatic factor was the most frequent one associated to the neuroendocrine one (28%). Ovulation was induced in 62.6% of the cases. Pregnancy was achieved in 65 patients (43.3%; 80% reached term, and 20% were abortions. PMID- 1860675 TI - [Effect of nifedipine on fetal heart rate in pre-eclamptic patients]. AB - From March 1st to October 31, 1989, we studied 23 women with diagnosis of severe preeclampsia, the gestational age in all of them was at least 34 weeks. A tococardiograph registry was obtained during 20 minutes prior to any management, after that a standardized management was started; nifedipine 10 mg sublingual was administered, and 20 minutes later, a new registry was obtained. In spite of a significative descent of arterial pressure, we did not find any significative change in the fetal heart rate, accelerations, variability, or in the fetal motility. PMID- 1860676 TI - [Inhibin, steroid hormone, and gonadotropin concentration in blood from fertile and infertile males and its relationship with testicular function]. AB - The role of inhibin in the testicular function and its relation with other hormone regulation spermatogenesis have not been elucidated in the human, therefore we studied by RIA the serum concentrations of this testicular secretion product, as well as those of LH, FSH, T and E2 and their possible correlation with some parameters evaluated by spermatobioscopy (cell number, motility, morphology and immature germinal cells) in fertile, oligozoospermic and azoospermic men. We did not find significant differences in inhibin concentration between fertile and oligozoospermic males; however in the azoospermic group the mean inhibin concentration was significantly higher (722.9 +/- 137.9 U/l in the fertile men; 658.5 +/- 147.1 and 963.1 +/- 300.9 U/l in the oligozoospermic and azoospermic groups respectively), in spite of data dispersion in the 3 study groups. Among the fertile males we found a negative significant correlation between the inhibin and the LH and FSH concentrations (p less than 0.05), while in the oligozoospermic patients this negative correlation was observed with T concentration. In the fertile males inhibin also showed correlation with the sperm percentage with normal morphology and with the immature germinal cells in semen; in the oligozoospermic group this glycoprotein showed correlation with the sperm count and the germinal cells concentration. We also found correlation between testosterone and/or LH concentrations and sperm count in both groups. These results indicate modifications in the hormonal concentrations regulating the testicular function and in their relationship, in men with testicular damage, which can render a change in the mechanisms controlling this function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860677 TI - [Effect of ultrafiltered peritoneal fluid from patients with pelvic endometriosis on the in vitro motility of their spouse's sperm]. AB - Recently, there has been information about the ultrafiltrated peritoneal fluid in patients with endometriosis, containing macromollecules that diminish tubal fimbria action, and the in vitro ovular captation in experimental animals. In order to investigate the presence of these substances in the peritoneal fluid, and to know the possible effect that could have on spermatic motivility in vitro, of their mates; 11 sterile women with diagnosis of pelvic endometriosis, and 11 normal fertile women, were studied. On the other side, the same day of study, the mate of each of these women, produced semen obtained by masturbation, where amount and motility of sperm, in basal conditions, and after, it was capacitated with Ham-F10, were determined. The final results was evaluated as to percentage of spermatozoon with excellent and progressive motility, and percentage of motionless spermatozoo as well as based on average values (mean +/- EE), of each one of them. The statistic analysis of differences was done by t Student that in coupled samples. The results confirm that peritoneal fluid of patient with endometriosis contains macromollecules, and it shows that these substances affect the motility in vitro of mate's spermatozoon, which could explain, partially at least, the origin of sterility in this disease. PMID- 1860678 TI - [Oxytocin. Use and abuse]. AB - From 1985 to 1988 we analyzed two hundred puerperas with term pregnancies and live newborns which pregnancy ended by vaginal route. One hundred of them received oxytocin during the labor and one hundred didn't receive it. The results showed that the use of oxytocin produces and increase in the cervical and vaginal tears; the Apgar score of the newborns was lower with a longer period in the incubator, and a high rate of complications regarding to respiratory distress and jaundice. These results were statistically significant according ti Chi square test with p less than 0.05. PMID- 1860679 TI - Association of a precore genomic variant of hepatitis B virus with fulminant hepatitis. AB - A variant of hepatitis B virus has been described recently in HBsAg+ Mediterranean patients who lack HBeAg and who have an unusual and severe form of chronic hepatitis. This variant is unable to produce HBeAg because of the presence of a novel translational stop codon at the end of the precore region of the genome. By direct sequencing of DNA, generated by the polymerase chain reaction, we have evaluated the association between infection with this variant and the fulminant course of hepatitis B. Eighteen patients with fulminant hepatitis B were studied. Of the 15 cases from whose serum viral DNA could be sequenced, the variant was found in the admission sera of 8 of 9 HBeAg- patients but in none of 6 HBeAg+ patients who had fulminant hepatitis B. Patients harboring the variant progressed more rapidly into hepatic encephalopathy, but those infected with the variant strain alone had a greater likelihood of survival than those infected with the normal strain or a mixture. The mutant strain may emerge spontaneously during fulminant hepatitis as occurs in chronic hepatitis B infection during seroconversion from HBeAg to antibody. Alternately, and perhaps less commonly, patients may be infected with the variant ab initio. PMID- 1860680 TI - A pathophysiological interpretation of unresponsiveness to spironolactone in a stepped-care approach to the diuretic treatment of ascites in nonazotemic cirrhotic patients. AB - It has been hypothesized that the magnitude of proximal sodium reabsorption affects the response to aldosterone antagonists in nonazotemic cirrhotic patients with ascites. To verify this hypothesis, we evaluated intrarenal sodium handling by lithium clearance in 51 nonazotemic ascitic cirrhotic patients and in 23 controls who were maintained on the same low-sodium diet (80 mmol/day). Seven of 51 cirrhotic patients underwent spontaneous diuresis, whereas 44 required diuretic treatment. Treatment was started with spironolactone at a dose of 150 mg once daily. The dose was increased to 300 mg and then to 500 mg once daily if no response ensued. Cirrhotic patients who did not experience ascites mobilization with 500 mg spironolactone were then treated with a combined diuretic regimen that included spironolactone at a fixed dose (500 mg once daily) and furosemide at an initial dose of 50 mg once daily. The dose was increased to 100, 150 and 200 mg once daily if no response was noticed. Response to diuretic treatment was defined as body weight loss greater than 700 gm every 3 days until ascites became clinically undetectable. Nonresponders (43%) to spironolactone showed lower sodium fractional excretion (0.34% +/- 0.28% vs. 0.80% +/- 0.50%; p less than 0.001) because of a lower fractional sodium delivery to the distal tubule (18.2% +/- 5.8% vs. 23.4% +/- 7.2%; p less than 0.025) than responders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860681 TI - Effect of oral propranolol administration on azygos, renal and hepatic uptake and output of catecholamines in cirrhosis. AB - Circulating catecholamines are increased in cirrhosis with portal hypertension, and increase further after propranolol. In 23 cirrhotic patients, plasma norepinephrine and epinephrine were determined in an artery, the azygos vein, the right renal vein and a hepatic vein before and after an oral 80-mg dose of propranolol. Baseline azygos and renal venous norepinephrine levels were significantly higher than arterial norepinephrine levels (+20%, p less than 0.005; and +28%, p less than 0.001, respectively). Hepatic venous norepinephrine and all venous epinephrine values were below the arterial values (all p less than 0.05). After propranolol intake, arterial norepinephrine and epinephrine increased (+16%, p less than 0.01; and +93%, p less than 0.001, respectively). Significant increases in norepinephrine and epinephrine were found in azygos and renal veins (all p less than 0.01), whereas hepatic venous norepinephrine and epinephrine remained unchanged. Azygos and hepatic blood flow decreased after propranolol intake (-27%, p less than 0.05; and -16%, p less than 0.01, respectively). Azygos spillover of norepinephrine (an estimate of locally released norepinephrine delivered to the circulation) and clearance of epinephrine remained unaltered. Hepatointestinal clearance showed no significant change for norepinephrine, but showed a borderline-significant decrease for epinephrine (-23%, p = 0.08). Our results show a net production of norepinephrine in the prehepatic splanchnic area drained through superior portalsystemic collaterals and in the kidneys. The increase in circulating catecholamines after propranolol intake is probably due to a combination of further enhancement of sympathetic activity and a decrease in catecholamine degradation. PMID- 1860682 TI - Antithrombin III supplementation reduces heparin requirement and platelet loss during hemodialysis of patients with fulminant hepatic failure. AB - Previous studies have shown that antithrombin III levels are low in fulminant hepatic failure, and heparin kinetics are abnormal, making control of heparinization difficult during hemodialysis of these patients who are at risk of bleeding. In this study, we have performed a controlled, randomized trial of antithrombin III supplementation on heparin activity, occurrence of bleeding and the platelet count and activation during hemodialysis in 24 patients with fulminant hepatic failure. The treated group of 12 patients was given 3,000 units of antithrombin III before hemodialysis. Antithrombin III supplementation was shown to normalize antithrombin III levels during hemodialysis (prelevels: 0.22 +/- 0.03 U/ml S.E.; at 1 hr 0.99 +/- 0.06 U/ml; p less than 0.001; control prelevels: 0.24 +/- 0.03 U/ml; at 1 hr 0.23 +/- 0.04 U/ml). Total heparin usage was significantly decreased by antithrombin III supplementation (median 5,200 U; range = 2,000 to 13,000) as compared with the control group (median 10,200 U; range = 5,000 to 16,500; p less than 0.005). Blood heparin level (antifactor Xa activity) after the initial bolus was significantly greater in the antithrombin III-supplemented subjects (0.40 +/- 0.07 U/ml compared with 0.22 +/- 0.05 U/ml in the control group; p less than 0.05). The significant reduction in platelet count observed in the control patients (18% +/- 6% at 1 hr; p less than 0.05) did not occur in antithrombin III patients (6% +/- 4% at 1 hr), which was reflected by a lower release of the platelet-specific protein beta-thromboglobulin. Two of 12 patients in both groups showed minor bleeding around vascular access sites during the first hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860683 TI - The metabolic bone disease of primary sclerosing cholangitis. AB - The incidence and severity of osteopenic bone disease in primary sclerosing cholangitis is poorly defined. Clinical, biochemical and radiographic assessment and bone mineral density measurements of the lumbar spine were carried out in two groups of patients. Group 1 consisted of 30 patients with advanced primary sclerosing cholangitis; group 2 consisted of 18 patients with newly diagnosed primary sclerosing cholangitis. Only one patient had bone pain. All patients were normocalcemic; two had elevated serum parathormone levels. Fourteen patients (47%) from group 1 but no patients from group 2 had low serum 25-hydroxyvitamin D levels. Mean bone mineral density was significantly reduced in group 1 patients (0.97 +/- 0.04 gm/cm2) compared with age-matched and sex-matched controls (1.25 +/- 0.01 gm/cm2, p less than 0.0001), and in 15 patients (50%) bone mineral density was below the fracture threshold (0.98 gm/cm2). The bone mineral density in group 2 was not significantly different from controls, and no patient was below the fracture threshold. In neither group did bone mineral density correlate with serum bilirubin, 25-hydroxyvitamin D, fecal fat excretion, previous drug therapy or the presence of chronic ulcerative colitis. Histomorphometrical examination of bone from four group 1 patients showed increased bone resorption, reduced bone formation, moderate-to-severe osteopenia and no osteomalacia. In conclusion, severe osteopenic bone disease is common in advanced primary sclerosing cholangitis and, like that seen in other cholestatis diseases, is consistent with osteoporosis. PMID- 1860684 TI - Graft vs. host disease after liver transplantation in humans: a report of four cases. AB - Four cases of patients in whom graft vs. host disease developed after liver transplantation are described. The clinical course of each patient was similar with fever, pancytopenia, diarrhea and a skin rash developing 1 or 2 mo after liver transplantation. The clinical diagnosis was made from skin or colon biopsy specimens. Liver dysfunction did not occur in the patients at the time of diagnosis. Extrahepatic donor DNA was identified in the three patients it was tested for. Three patients died from the complications of the disease primarily related to sepsis. The other patient recovered from the graft vs. host disease but died from lymphoproliferative disease. PMID- 1860685 TI - Rates of vertebral bone loss before and after liver transplantation in women with primary biliary cirrhosis. AB - Atraumatic fractures caused by osteoporosis may be a serious complication of primary biliary cirrhosis. Mean (+/- S.D.) bone mineral density in the lumbar spine in 210 ambulatory women with primary biliary cirrhosis was 1.02 +/- 0.19 gm/cm2, 7% lower than that in 139 age-matched normal women (after adjustment for age and body weight) (p less than 0.001). Bone mineral density in the lumbar spine was inversely related to a risk score index of liver disease severity (r = 0.29, p less than 0.001). The mean rate of bone loss in 105 of these 210 women was 2%/yr +/- 4%/yr, twice as great as in the 139 normal women (p less than 0.02). In 20 women with primary biliary cirrhosis followed up after orthotopic liver transplantation, bone mineral density in the lumbar spine decreased at 3 mo (p less than 0.01), and this decrease may have resulted in atraumatic fractures in 13 of them. Bone mineral density in the lumbar spine then increased (p less than 0.01) so that by 12 mo the median bone mineral density in the lumbar spine was similar to that before transplantation and by 24 mo it was 5% above it. Therefore we conclude that the progressive bone loss observed in primary biliary cirrhosis (which is further accentuated immediately after transplantation) may be halted, and the bone mass may be restored toward normal within 2 to 3 yr after orthotopic liver transplantation. PMID- 1860686 TI - In vitro fragmentation of gallstones: comparison of electrohydraulic, electromagnetic and piezoelectric shockwave lithotripters. AB - To compare the fragmentation efficiency of three different shockwave systems, 63 human gallstone triplets were disintegrated in vitro using an electrohydraulic (MPL 9000, Dornier), an electromagnetic (Lithostar Plus, Siemens) and a piezoelectric (Piezolith 2300, R. Wolf) lithotripter. Since each stone triplet was obtained from the same gallbladder, the concrements of one such set were identical in physicochemical parameters. According to the maximal diameter, the calculi were divided into group A (6 to 15 mm) and group B (16 to 30 mm). Shockwave application was terminated when residual fragments measured 4 mm or less. Forty-five triplets were fragmented at energy settings mainly used in clinical treatment of patients with gallbladder stones (MPL 9000: 20 kV; Lithostar Plus: setting 9 (maximal); Piezolith 2300: setting 3). The fragmentation endpoint was achieved in group A (n = 3 x 36) with the Piezolith 2300 after median 150 (range = 50 to 500) pulses and with the Lithostar Plus after 150 (50 to 750) pulses compared with 500 (50 to 1,500) pulses using the MPL 9000 (p less than 0.01). In group B (n = 3 x 9) the Lithostar Plus (median = 750, range = 250 to 1,250 pluses) required fewer discharges than the Piezolith 2300 (1,250, 250 to 2,500 pulses; p less than 0.05) and the MPL (1,500, 500 to 1,600 [upper limit] pulses; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860687 TI - Changes in sulfated proteoglycan production after activation of rat liver macrophages. AB - Production of extracellular matrix proteins-in particular, the proteoglycans-by macrophages is important in many of their functions, including cell-cell recognition, adhesion and phagocytosis. In this study, we characterized changes in sulfated proteoglycan production by hepatic macrophages following in vivo activation with lipopolysaccharide. We found that both resident Kupffer cells and liver macrophages from lipopolysaccharide-treated rats incorporated [35S]sulfate into proteoglycans. Lipopolysaccharide-activated macrophages incorporated two to three times more of the label than did resident Kupffer cells. In addition, although both cell types produced chondroitin sulfate and heparan sulfate, resident Kupffer cells synthesized more chondroitin sulfate whereas lipopolysaccharide-activated cells produced more heparan sulfate. Using specific antibodies and flow cytometry, we also found that hepatic macrophages produced chondroitin-4-sulfate, chondroitin-6-sulfate and chondroitin-O-sulfate. Lipopolysaccharide-activated macrophages contained more chondroitin-4-sulfate and chondroitin-O-sulfate and less heparan sulfate than did resident Kupffer cells. Both tunicamycin and beta-D-xylosides, inhibitors of sulfated proteoglycan biosynthesis, were found to block phagocytosis by the cells. Taken together, these results suggest that sulfated proteoglycans are important in activation and functional responsiveness of liver macrophages. PMID- 1860688 TI - Bacterial invasion of the biliary system by way of the portal-venous system. AB - It has been suggested that bacteria in the intestine gain access into the biliary tract by entering the portal-venous blood. We have tested the hypothesis of hematogenous infection of the biliary system in cats. The animals were treated in three different groups: group A (no biliary obstruction), group B (acute biliary obstruction) and group C (chronic biliary obstruction). A mutant strain of Escherichia coli was infused into the splenic vein of cats at three different dosages (10(7), 10(5) and 10(3) with sham controls. In the unobstructed biliary system, the mutant E. coli was isolated from the bile 30 min and 90 min after the infusion of 10(7) and 10(5) E. coli, respectively. No bacteria were found in the bile with the infusion of 10(3) E. coli and in the control animals. Bile flow was significantly reduced with the infusion of bacteria. The biliary excretion of E. coli in group B was similar to that in group A. In group C, the bile output in the first hour was very high but declined rapidly. E. coli was excreted into the bile at all three dosages of infusion after 30 min. Histological sections of the liver showed that the infused bacteria entered the sinusoidal blood and that some were phagocytosed by Kupffer cells. The portal-venous blood was considered an important route of bacterial invasion into the biliary system, and the penetration of bacteria was facilitated in biliary obstruction. PMID- 1860689 TI - Prevention of portal hypertension and portosystemic shunts by early chronic administration of clonidine in conscious portal vein-stenosed rats. AB - The hemodynamic effects, including mesenteric-systemic shunts of early chronic administration of clonidine, were studied in conscious, unrestrained, portal vein stenosed rats. In rats receiving early chronic clonidine (600 micrograms.kg-1.day 1 by gavage), begun 3 days before portal vein stenosis and then administered continuously for 10 consecutive days, portal pressure (10.0 +/- 1.5 mm Hg) and degree of mesenteric-systemic shunts (58% +/- 25%) were significantly lower than in the placebo group (15.2 +/- 1.5 mm Hg and 83% +/- 7%, respectively). The effects were observed either 2 to 3 hr or 18 to 24 hr after the last dose of clonidine. In rats receiving clonidine continuously for 5 days, starting 5 days after portal vein stenosis, portal pressure (11.0 +/- 1.3 mm Hg) was significantly lower than in the placebo group, but mesenteric-systemic shunts (82% +/- 8%) were not significantly different. In rats receiving a single oral dose of clonidine (600 micrograms/kg) 10 days after portal vein stenosis, portal pressure (11.8 +/- 2.1 mm Hg), measured 2 to 3 hr after clonidine administration, was significantly lower than in the placebo group. Mesenteric-systemic shunts (83% +/- 8%), however, were not significantly different from the placebo group. In addition, 18 to 24 hr after a single dose of clonidine, hemodynamic values returned to basal conditions. We also demonstrated that chronic clonidine administration begun before portal vein stenosis can reduce the initial increase in portal pressure after this procedure. We concluded that early chronic clonidine administration reduces the severity of portal hypertension and the development of portosystemic shunts in portal vein-stenosed rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860690 TI - Functional and morphological features of isolated hepatocytes preserved in University of Wisconsin solution. AB - Although several studies suggest that hepatic graft failure after cold ischemia results from nonparenchymal cell damage, other data indicate that hepatocellular ATP content is significantly correlated with the transplantation success rate. In this study, we have conducted a systematic investigation of various aspects of cell viability and function of isolated hepatocytes stored at 4 degrees C for 24 and 48 hr in either University of Wisconsin solution or Hanks' HEPES buffer, a control solution clinically unsuitable for organ preservation. After 24 hr, hepatocytes stored in Hanks' HEPES buffer had viability (measured by trypan blue exclusion and ALT and lactic dehydrogenase leakage), transport function (measured by 22Na+ and [3H]taurocholate uptake) and cell size similar or only slightly altered when compared with freshly isolated and University of Wisconsin solution stored hepatocytes. ATP content was decreased in both groups; however, the reduction was much greater in Hanks' HEPES buffer-stored cells. Furthermore, ATP regenerating capacity was greatly reduced in Hanks' HEPES buffer- stored but not in University of Wisconsin solution-stored hepatocytes. By 48 hr viability and function of Hanks' HEPES buffer-stored hepatocytes were decreased; University of Wisconsin solution afforded partial protection. When examined by light and electron microscopy, cells stored in both University of Wisconsin solution and Hanks' HEPES buffer for 24 hr appeared essentially normal except for the presence of numerous membrane blebs in the Hanks' HEPES buffer group. Tissue sections of livers preserved in Hanks' HEPES buffer but not in University of Wisconsin solution revealed the presence of extensive amounts of blebs in the sinusoidal lumen and loss of endothelial elements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860691 TI - A comparison of lipoprotein secretion, bile production and hepatic morphology in isolated rat livers perfused with a perfluorocarbon emulsion or rat erythrocytes. AB - Isolated rat livers were perfused with an oxygenated perfluorocarbon emulsion, FC 43 emulsion for 1 to 4 hr. FC-43 emulsion contained 20% FC-43 (wt/vol) perfluorotributylamine (the fluorocarbon component for the transport of oxygen and carbon dioxide) emulsified with 2.56% Pluronic F-68 (a nonionic surfactant) in Krebs-Ringer bicarbonate buffer. FC-43 emulsion also contained 3% hydroxyethyl starch as an oncotic agent and 1.8 mg/ml glucose. The viability (oxygen consumption), bile secretion, structural integrity and secretion of nascent lipoproteins by FC-43-perfused rat livers was compared with livers perfused with Krebs-Henseleit bicarbonate buffer that contained rat erythrocytes (25% hematocrit) and 1.5 mg/ml glucose (red blood cell medium). Oxygen consumption was somewhat higher in livers perfused with FC-43 emulsion. Bile secretion of livers perfused with FC-43 emulsion for 4 hr was reduced significantly to 40% of that by red blood cell medium. The structural integrity of livers perfused with FC-43 emulsion varied from normal to marked cellular damage. Light-microscopical examination of rat livers perfused with FC-43 emulsion showed ballooning of sinusoids, presence of vacuoles in sinusoidal lining cells in some hepatocytes and detachment of endothelium in sinusoids. The number of vacuoles progressively increased in longer perfusions. Electron-microscopical studies showed the presence of small (60 to 100 nm) vesicles of varying electron density, presumably fluorocarbon particles inside the vacuoles in sinusoidal lining cells (Kupffer and endothelial) and hepatocytes. After 4 hr of perfusion with FC-43 emulsion, most of the sinusoidal endothelia were denuded, and the microvilli of the hepatocytes all but disappeared. In contrast, the ultrastructure of rat livers perfused with red blood cell medium for 4 hr was unaltered. The accumulation of nascent lipoproteins in perfusates of FC-43-perfused livers was markedly reduced, and no normal very-low-density lipoprotein, low-density lipoprotein or high density lipoprotein were isolated. Chemical analysis showed the presence of Pluronic F-68 in all lipoprotein fractions. Our data strongly suggest that, during recirculating liver perfusions with FC-43 emulsion (between 1 and 4 hr), the nonionic surfactant detergent Pluronic F-68 dissociated from the emulsion and markedly affected hepatic structure, lipoprotein secretion and the composition of lipoproteins isolated from perfusate. Therefore FC-43 emulsion is not a suitable liver-perfusion medium for studies of lipoprotein metabolism. PMID- 1860692 TI - Biliary excretion of bile acid conjugates in a hyperbilirubinemic mutant Sprague Dawley rat. AB - The hepatic transport of bile acid conjugates was studied in the Eisai hyperbilirubinuria rat, a Sprague-Dawley mutant rat with conjugated hyperbilirubinemia. Serum bile acid levels were increased, bile acid-independent bile flow was decreased and biliary glutathione concentrations were markedly decreased in the Eisai hyperbilirubinuria rat. Biliary excretion of sulfobromophthalein was markedly impaired and almost no glutathione conjugate was excreted in the bile of the Eisai hyperbilirubinuria rat. Biliary excretion of lithocholate-3-O-glucuronide and lithocholate-3-sulfate in the Eisai hyperbilirubinuria rat was markedly delayed, whereas that of lithocholate was only slightly delayed. After [14C]chenodeoxycholate infusion (1 mumol/min/100 gm for 60 min), the increases in bile flow and biliary excretion of isotope in the Eisai hyperbilirubinuria rat were not so prominent as those observed in control rats, and the glucuronide of chenodeoxycholate, which constituted about 15% of biliary chenodeoxycholate in control rats, was not observed in the Eisai hyperbilirubinuria rat. Initial uptake of lithocholate and its glucuronide and sulfate by isolated hepatocytes was not impaired in the Eisai hyperbilirubinuria rat; the profiles of cytosolic bile acid binding proteins in Eisai hyperbilirubinuria rat liver were identical to those in control liver. These data indicate that the Eisai hyperbilirubinuria rat has excretory impairment of organic anions, bile acid glucuronide and sulfate and that it has characteristics very similar to those of the hyperbilirubinemic mutant Wistar rats TR- and GY. PMID- 1860693 TI - Minor contribution of hepatocytes to collagen production in normal and early fibrotic rat livers. AB - Hepatocyte contribution to hepatic collagen production in vivo was estimated in rats, based on the fact that ornithine is used for protein synthesis in the liver as arginine after conversion by way of the urea cycle only by hepatocytes. From rats given a mixture of [14C] ornithine and [3H]arginine, hepatic collagen and serum albumin were obtained. The hepatocyte contribution was calculated from the 14C and 3H in arginine purified from collagen and albumin by high performance liquid chromatography. The contribution was less than 10% of total collagen production in normal and early fibrotic livers induced by a single dose of carbon tetrachloride or dimethylnitrosamine. We conclude that hepatocytes may play a minor role in collagen production in normal and early fibrotic rat livers. PMID- 1860694 TI - Kupffer cell prostaglandin-E2 production is amplified during hepatic regeneration. AB - Prostaglandin-E2 increases in liver tissue after partial hepatectomy and stimulates DNA synthesis in primary cultures of hepatocytes. This study evaluated the capacity of Kupffer cells isolated at various intervals after partial hepatectomy to produce prostaglandin E2 in response to bacterial endotoxin. This stimulator of Kupffer cells is a normal endogenous component of portal venous blood. After partial hepatectomy (6 to 48 hr), when hepatic regeneration rates were greatest, regenerating liver Kupffer cells demonstrated a significantly greater capacity to produce prostaglandin E2 in response to bacterial endotoxin than did equal numbers of Kupffer cells from time-matched, sham-operated control animals. However, by 12 days after partial hepatectomy, when liver mass had been more than 83% restored, regenerating liver Kupffer cell prostaglandin E2 production had decreased to levels produced by sham KC. We postulate that high levels of Kupffer cell-derived prostaglandin E2 provide a critical paracrine signal fundamental to the initiation and control of growth by neighboring hepatocytes during liver regeneration. PMID- 1860695 TI - Facilitated diffusion and sodium-dependent transport of purine and pyrimidine nucleosides in rat liver. AB - In mammalian cells, nucleoside transport usually is mediated by facilitated diffusion. In addition, a Na(+)-dependent, concentrative nucleoside transport system has been detected in several tissues but not the liver. To further clarify hepatic nucleoside transport mechanisms, we measured the uptake of [2-14C]uridine (2 to 100 mumol/L) and of [8-14C]adenosine (10 to 75 mumol/L) by the isolated perfused rat liver in the presence or absence of extracellular sodium or specific inhibitors of facilitated nucleoside diffusion. Uridine transport and metabolism were monitored by the release of labeled catabolites including 14CO2, which indicated complete degradation of the pyrimidine. Adenosine, uridine and uridine catabolites were measured in the effluent perfusate by reversed-phase high performance liquid chromatography and a radioactivity flow monitor. The existence of a Na(+)-dependent nucleoside transport system could be inferred from the following observations: (a) Sodium depletion caused a strong inhibition of nucleoside transport reflected by an up to threefold and 15-fold increase in extracellular uridine and adenosine, respectively. The sodium-dependent transport of uridine was saturated when the influent uridine concentration was raised beyond 20 mumol/L. No such saturation was observed for much higher concentrations of adenosine used (10 to 75 mumol/L). (b) Na(+)-free perfusion resulted in a strong suppression of the release of uridine catabolites by the liver. Complete uridine breakdown was depressed to 7% of the amount of 14CO2 released in the presence of sodium and at influent uridine concentrations below 20 mumol/L. (c) Inhibition of uridine (10 mumol/L) transport and degradation was observed after coperfusion with adenosine, deoxyadenosine, guanosine and deoxyguanosine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860696 TI - Tumor necrosis and alcoholic hepatitis. PMID- 1860697 TI - Predicting drug interactions using cultured human hepatocytes. PMID- 1860698 TI - "Posterior" gastric vein, okay. But let's not forget the "collateral" gastric vein. PMID- 1860699 TI - The role of preS1 in the interaction of hepatitis B virus with human hepatocytes. PMID- 1860700 TI - A three-dimensional motion model of loads on the lumbar spine: I. Model structure. AB - Traditionally most biomechanical models that are used to estimate the loading experienced by the spine during work focus on static, two-dimensional representations of the work. However, most work tasks impose loads on the lumbar spine under dynamic, three-dimensional conditions. The objective of this study was to describe the structure and logic of a model that is capable of producing estimates of spine loading under three-dimensional motion conditions. This model is intended for use primarily under laboratory conditions. The model was designed initially for workplace simulation in which the trunk is moving under symmetric and asymmetric constant velocity lifting conditions. Future embellishments may enable the model to be used under free dynamic conditions. The model predicts lumbar spine compression, shear, and torsional forces as well as trunk torque production continuously throughout the exertion. This information may be compared with spine tolerance limits so that the risk of causing a vertebral end-plate microfracture by workplace requirements could be determined. PMID- 1860701 TI - A three-dimensional motion model of loads on the lumbar spine: II. Model validation. AB - A three-dimensional motion model has been developed that estimates loads on the lumbar spine under laboratory conditions that simulate manual materials handling conditions. Eleven subjects experienced spinal loading during an experiment in which conditions of trunk velocity, trunk torque output, and trunk asymmetric posture were varied in a series of isokinetic velocity trunk extensions. The electromyographic activity of 10 trunk muscles, subject anthropometry, and trunk kinetics were used as input to a biomechanical simulation model described in Part I of this study. The model calculated estimates of compression, shear, and torsion loading in the lumbar spine, as well as the torque production of the trunk, continuously throughout the exertion. Trunk torque estimates derived from this model were compared with measured trunk torque. The effects of trunk motion, posture, and torque level on spine loading as estimated by the model are discussed. It was concluded that this approach provides a straightforward means of assessing loading of the spine attributable to laboratory simulations of workplace conditions. PMID- 1860702 TI - Work posture, workstation design, and musculoskeletal discomfort in a VDT data entry task. AB - Self-report data on musculoskeletal discomfort were collected from several hundred VDT users in two agencies of a state government. Aspects of worker posture and workstation design were objectively assessed for 40 of the VDT users. Multiple regression analyses were used to examine the relationship between these ergonomic variables and musculoskeletal discomfort. Effects of ergonomic factors on musculoskeletal discomfort were clearly evident in the analyses. Regression models explained up to 38% of the variance in discomfort at different body sites. Of special interest was that leg discomfort increased with low, soft seat pans, suggesting that postural constraint is more important than thigh compression as a risk factor for leg discomfort in VDT work. In addition, arm discomfort increased with increases in keyboard height above elbow level, supporting arguments for low placement of the keyboard. Finally, high levels of neck and shoulder girdle discomfort observed in the study population suggest the need for further attention to the control of cervicobrachial pain syndromes in VDT work. PMID- 1860703 TI - Improving auditory warning design: relationship between warning sound parameters and perceived urgency. AB - This paper presents an experimental study of the effects of individual sound parameters on perceived (psychoacoustic) urgency. Experimental Series 1 showed that fundamental frequency, harmonic series, amplitude envelope shape, and delayed harmonics all have clear and consistent effects on perceived urgency. Experimental Series 2 showed that temporal and melodic parameters such as speed, rhythm, pitch range, and melodic structure also have clear and consistent effects on perceived urgency. The final experiment tested a set of 13 auditory warnings generated by an application of the earlier experimental findings. The urgency rank ordering of this warning set was predicted, and the correlation between the predicted and the obtained order was highly significant. The results of these experiments have a widespread application in the improvement of existing auditory warning systems and the design of new systems, where the psychoacoustic and psychological appropriateness of warnings could be enhanced. PMID- 1860704 TI - Renal arteriolar diameters in spontaneously hypertensive rats. Vascular cast study. AB - The relation between the arteriolar diameters and hypertensive glomerulosclerosis was studied by using microvascular casts and histological evaluation. Spontaneously hypertensive rats 4 weeks of age were divided into three groups: nontreated, captopril (40 mg/kg/day)-treated, and trichlormethiazide (1 mg/kg/day) with hydralazine (20 mg/kg/day)-treated. Wistar-Kyoto rats served as controls. At 6 weeks old, the captopril-treated rats showed a lower blood pressure and a larger afferent arteriolar diameter compared with the control rats. At 20 weeks old, the nontreated group exhibited hypertension and a lower arteriolar diameter ratio (afferent to efferent, 0.89 versus 1.22 in control group) because of afferent constriction and efferent dilatation, seen equally in the outer and inner cortexes. Glomerulosclerosis was accentuated only in the inner cortex of the nontreated group (score, 63 versus 29 in control group). In the two treated rat groups, the blood pressure was reduced and arteriolar diameter ratios were similar to those in the control group (1.18 and 1.26). The sclerosis score in the trichlormethiazide with hydralazine-treated rats (score, 26) was lower than in the nontreated rats but not the captopril-treated rats (score, 36). These results indicated that 1) in the hypertensive rats, despite a reduced diameter ratio, glomerulosclerosis was more severe in the inner cortex; 2) two therapies reduced blood pressure and reversed the arteriolar changes, but a decrease in glomerulosclerosis was seen only in the trichlormethiazide with hydralazine-treated rats; and 3) for development of glomerulosclerosis, factors other than hemodynamics may be important in addition to intraglomerular pressure. PMID- 1860705 TI - Abnormal platelet and lymphocyte calcium handling in prehypertensive rats. AB - We have reported that the basal and stimulated cytosolic free calcium concentrations [( Ca2+]i) are elevated in platelets isolated from 12-14-week-old spontaneously hypertensive rats (SHR) as compared with normotensive Wistar-Kyoto (WKY) rats. To determine whether altered cell calcium metabolism precedes the development of overt hypertension, we measured [Ca2+]i under resting and stimulated conditions in blood platelets and thymic lymphocytes isolated from 4 week-old prehypertensive SHR and WKY rats. Blood pressure was similar in both groups (SHR 95 +/- 8 versus WKY rats 92 +/- 7 mm Hg). Basal [Ca2+]i in platelets was higher in SHR than WKY rats (63.4 +/- 3.9 versus 54.8 +/- 3.1 nM, p less than 0.003). Also the [Ca2+]i response to thrombin was greater in SHR than WKY rats in both the presence and absence of extracellular calcium. For lymphocytes, although no difference was detected in basal [Ca2+]i, the concanavalin A-induced peak [Ca2+]i was higher for SHR than WKY rats in both calcium-containing and calcium free media. These results suggest that agonist-stimulated calcium influx and calcium discharge from intracellular stores are enhanced in both platelets and lymphocytes of 4-week-old SHR. We conclude that abnormalities in calcium metabolism in two different cell types precede the development of overt hypertension in the SHR. PMID- 1860706 TI - Platelet-free calcium and vascular calcium uptake in ethanol-induced hypertensive rats. AB - This study examined the effect of moderate ethanol intake on systolic blood pressure, platelet cytosolic free calcium, aortic calcium, and rubidium-86 uptake in Wistar-Kyoto rats. Twelve Wistar-Kyoto rats, aged 6 weeks, were given 5% ethanol in drinking water the first week followed by 10% ethanol in drinking water for the next 6 weeks. Twelve control animals were given regular tap water. Systolic blood pressure in the ethanol-treated rats was significantly higher (p less than 0.05) than that in controls after 1 week and remained higher throughout the study. At 13 weeks of age, platelet cytosolic free calcium and calcium uptake by aortas were significantly higher (p less than 0.001) in ethanol-treated animals as compared with those in controls. Ethanol intake did not affect aortic ouabain-sensitive 86Rb uptake. The in vitro effect of ethanol on calcium-45 and 86Rb uptake was also investigated in aortas of untreated Wistar-Kyoto rats at 13 weeks of age. In vitro ethanol (2.5-20 mmols/l) did not significantly affect 45Ca and 86Rb uptake in rat aortas. The increases in systolic blood pressure, platelet cytosolic free calcium, and vascular calcium uptake suggest that increases in cytosolic free calcium and calcium uptake mechanisms are associated with ethanol induced hypertension. PMID- 1860708 TI - Reversal of low dose angiotension hypertension by angiotensin receptor antagonists. AB - During acute angiotension II (Ang II) infusion (200 ng/kg/min i.v.) into anesthetized rats, mean arterial pressure rose from 124 +/- 1 to 154 +/- 2 mm Hg. The peptidic Ang II antagonist saralasin lowered arterial pressure in a dose dependent manner. The maximal decrease in pressure was similar to that observed after the Ang II infusion was discontinued. The nonpeptide Ang II antagonist, 4' [( 2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazole-1-yl] methyl) [1,1'-biphenyl] 2-carboxylic acid (SC-48742), lowered acutely elevated arterial pressure to a level similar to that on discontinuation of the angiotensin infusion. Chronic (8 days) infusion of Ang II (20 ng/kg/min i.v.) increased mean arterial pressure from 116 +/- 3 to 164 +/- 7 mm Hg, which then decreased to 121 +/- 6 mm Hg on termination of the infusion. Saralasin (10 micrograms/kg/min, a maximally effective dose during acute angiotensin infusion) decreased mean arterial pressure from 168 +/- 7 to 141 +/- 3 mm Hg, a pressure significantly higher (p less than 0.05) than the pressure observed after the angiotensin infusion was discontinued. SC-48742 decreased mean arterial pressure from 167 +/- 7 to 127 +/- 3 mm Hg, a pressure not statistically different from the minimum pressure observed after the angiotensin infusion was terminated. The mechanism of blood pressure elevation during acute high dose or chronic low dose Ang II infusion is different, the latter having a significant neural component as measured by the response to trimethaphan. The peptidic antagonist saralasin was fully effective in lowering acute angiotensin hypertension but only partially effective during chronic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860707 TI - Genetic heterogeneity of the spontaneously hypertensive rat. AB - We examined DNA fingerprints of the spontaneously hypertensive rat from Shimane Institute of Health Science, Izumo, Japan, including seven substrains that were separated in the early stages of the establishment of the stroke-prone spontaneously hypertensive rat, and compared their fingerprints with those of rats from other sources. Obtained DNA fingerprints revealed that, in both the stroke-resistant spontaneously hypertensive rat and the Wistar-Kyoto rat, there is a substantial genetic difference between the rats from the National Institutes of health and from Shimane Institute of Health Science. By contrast, only a small genetic difference was observed either between the rats from the National Institutes of Health and Charles River Laboratories or among the substrains of the spontaneously hypertensive rat in the Shimane Institute of Health Science. Further, in the strains from the Shimane Institute of Health Science, there were fingerprinting bands that could distinguish either the Wistar-Kyoto rat from all the substrains of the spontaneously hypertensive rat or the stroke-prone from the stroke-resistant spontaneously hypertensive rat in spite of their close genetic backgrounds. From the observations above, we concluded 1) that there is substantial genetic variance of the spontaneously hypertensive rat between the two major sources in the world, the National Institutes of Health and the Shimane Institute of Health Science and 2) that by DNA fingerprinting analysis, it is possible to identify the restriction fragment length polymorphisms that are specific for the spontaneously hypertensive rat or the stroke-prone spontaneously hypertensive rat. These polymorphisms can be applied in the segregation study of the F2 generation. PMID- 1860709 TI - Human astrocytes contain two distinct angiotensin receptor subtypes. AB - The ability of angiotensin peptides to stimulate prostaglandin release and raise intracellular calcium levels by activating a phosphoinositide-specific phospholipase C was assessed in three human astrocytoma cell lines (CRTG3, STTG1, and WITG2). The addition of angiotensin II to CRTG3 cells resulted in a dose dependent release of prostaglandin E2 and prostacyclin, the production of inositol 1,4,5-trisphosphate, and the mobilization of intracellular calcium. Angiotensin-(1-7), previously considered to be an inactive metabolite of angiotensin II, was as potent as angiotensin II for prostaglandin release but did not activate phospholipase C or mobilize intracellular calcium. In contrast, angiotensin-(2-8) caused only a slight increase in prostaglandin release, even though it was as effective as angiotensin II in augmenting inositol 1,4,5 trisphosphate production and calcium mobilization. Moreover, neither the release of prostaglandins in response to angiotensin II or angiotensin-(1-7) nor the mobilization of intracellular calcium in response to angiotensin II required extracellular calcium. Angiotensin II and angiotensin-(1-7) caused the release of prostaglandins from all three human astrocytoma cell lines, but changes in the level of intracellular calcium in response to angiotensin II only occurred in CRTG3 cells. Although previous studies have provided evidence for angiotensin receptor subtypes on the basis of selectivity of antagonists or signal transduction mechanisms, these data suggest that human astrocytes contain multiple angiotensin receptor subtypes on the basis of their response to different angiotensin heptapeptides--angiotensin-(1-7) and angiotensin-(2 8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860710 TI - Attenuated vascular reactivity in dogs with anteroventral third ventricle lesions. AB - Lesion of the anteroventral portion of the third cerebral ventricle causes hypernatremia, adipsia, and attenuation of the pressor response to intravenous administration of angiotensin II and norepinephrine. In addition, these lesions prevent the development of several experimental models of hypertension. In this study, a lesion of the third cerebral ventricle region was made in 14 dogs. In seven dogs in which hypernatremia developed the lesions included the organum vasculosum of the lamina terminalis; seven animals in which the circumventricular organ was spared by the lesion remained normonatremic. Vascular responsiveness of isolated right carotid artery rings to angiotensin II and phenylephrine was assessed 3 days after lesioning the anteroventral portion of the third cerebral ventricle. In endothelium-denuded ring vessels, vasoconstrictor responses to phenylephrine were significantly decreased in animals both with and without inclusion of the organum vasculosum of the lamina terminalis. A similar effect was observed in intact vessels of dogs in which the circumventricular organ was spared but not in those with lesions that included this area. In contrast, angiotensin II-induced vasoconstriction was significantly decreased in the arteries with intact endothelium of both groups of lesioned animals. These data show that lesion of the anteroventral third ventricle area alters alpha 1 adrenergic and angiotensin II vascular responsiveness in isolated carotid artery rings with the possible participation of the endothelium. PMID- 1860711 TI - Cardiovascular responses to bicuculline in the paraventricular nucleus of the rat. AB - The present study was undertaken to determine whether gamma-aminobutyric acid in the paraventricular nucleus contributes to the regulation of cardiovascular function. Blood pressure and heart rate were recorded and plasma catecholamines were measured in conscious rats receiving microinfusions of either artificial cerebrospinal fluid or a gamma-aminobutyric acid antagonist, bicuculline methiodide, bilaterally into the paraventricular nucleus. Artificial cerebrospinal fluid had no effect on any of the recorded variables. In contrast, infusion of bicuculline into the region of the paraventricular nucleus produced increases in blood pressure (20 +/- 2 mm Hg), heart rate (110 +/- 11 beats/min), and plasma concentrations of norepinephrine (640 +/- 107 pg/ml) and epinephrine (1,266 +/- 267 pg/ml). Pretreatment with a ganglionic blocking agent abolished both the blood pressure (-1 +/- 2 mm Hg) and heart rate (5 +/- 18 beats/min) effects. Bilateral adrenal medullectomy reduced the changes in plasma norepinephrine concentrations (81 +/- 14 pg/ml) significantly and abolished the changes in plasma epinephrine concentrations (5 +/- 4 pg/ml). Conversely, adrenal medullectomy reduced the pressor effects (18 +/- 2 mm Hg) only slightly while the heart rate responses were attenuated (42 +/- 9 beats/min) by approximately 50%. These results suggest that an endogenous gamma-aminobutyric acid system exerts a tonic inhibitory effect on the sympathetic nervous system at the level of the paraventricular nucleus of the hypothalamus. PMID- 1860712 TI - Does regional norepinephrine spillover represent local sympathetic activity? AB - Regional spillover of norepinephrine (NE), based on isotope dilution and single compartment steady-state kinetics, is considered one of the best parameters for estimating organ sympathetic activity. However, the effects of local changes in clearance of NE on the spillover have not yet been investigated. We studied local NE kinetics and clearance in the forearm of 10 healthy subjects using intra arterial infusions of NE, tritiated NE, the neuronal uptake inhibitor desipramine, and tyramine, which competes with NE for the neuronal uptake carrier. Before and during complete blockade of neuronal uptake by desipramine the venous concentration-time curves for tritiated NE and for NE released by tyramine were biexponential, consistent with the presence of (at least) two compartments for circulating tritiated NE and for locally released NE. The time constants for tyramine-induced release of NE and, in the same subjects during desipramine infusion, for tritiated NE were almost equal at the same level of forearm blood flow. This argues against possible diffusion or transport differences for NE to and from the circulation and the synapse. The regional intrinsic clearance capacity (a measure of the maximal ability of an organ to irreversibly remove drug by all pathways in the absence of any flow limitations) for NE decreased in the forearm by 65% (p less than 0.01) during neuronal uptake blockade by desipramine; the forearm clearance decreased by 59% (p less than 0.001), whereas the spillover rate of NE increased from 33 +/- 5 to 63 +/- 11 pmol.min-1 (p less than 0.05). Nitroprusside-induced increments in blood flow increased the spillover of NE from 18 +/- 4 to 35 +/- 6 pmol.min-1 (p less than 0.01); the clearance of circulating NE also increased (by 58%, p less than 0.05), and the intrinsic clearance capacity remained unchanged. This demonstrates that regional spillover of NE is markedly influenced by local changes in clearance and flow. The new parameter plasma appearance rate of NE is proposed. Although also derived from isotope dilution, this parameter may better approximate the regional entry of NE into the blood pool than spillover. This is corroborated by the nonsignificant changes of plasma appearance rate of NE during our desipramine and nitroprusside infusions. PMID- 1860713 TI - Sodium and volume sensitivity of blood pressure. Age and pressure change over time. AB - Salt sensitivity has been implicated in the age-related increase in blood pressure. We studied the reproducibility of a rapid method for assessing sodium sensitivity and resistance of blood pressure as well as the effect of age on this phenomenon. Blood pressure after volume expansion with 2 l intravenous saline (0.9%) over 4 hours was compared with that after 1 day of 10 mmol sodium chloride intake and 3 and 40 mg oral doses of furosemide. Normal and hypertensive subjects (n = 28) were studied twice within a year. Cross-sectional observations of the effect of age were made from studies in 230 hypertensive and 430 normotensive subjects. Longitudinal observations of blood pressure change over time were made 10 or more years after categorization of sodium responsivity in 31 subjects. The blood pressure response was reproducible in 28 subjects studied twice (r = 0.56, p less than 0.002). Four subjects changed salt-responsiveness status and six were indeterminate on restudy. Sodium sensitivity of blood pressure increased significantly with increasing age in the entire population (n = 660, r = -0.38, p less than 0.001). The relation was more striking in hypertensive subjects (n = 230, r = -0.31, p less than 0.001) in whom a progressive increase in salt sensitivity with decades was seen than in the normotensive group (n = 430, r = 0.19, p less than 0.01) in whom salt sensitivity was not observed until the sixth decade. Salt-sensitive subjects had a significantly greater increase in systolic (p less than 0.001) and diastolic (p less than 0.01) pressure over time than those who were salt-resistant. Salt sensitivity is a reproducible phenomenon that is related to the age-associated increase in blood pressure characteristic of industrialized societies. In addition, salt sensitivity can be shown to be a predictor of subsequent, age-related blood pressure increase. PMID- 1860714 TI - Prevalence of Type A behavior in untreated hypertensive individuals. AB - Type A behavior has been associated with coronary heart disease as well as high cholesterol and smoking, major risk factors for coronary heart disease, but the data indicating a similar association with hypertension are inconsistent. Since past studies have usually based hypertension on a single blood pressure assessment or have often included treated hypertensive patients, this inconsistency is not surprising. The current study compared the prevalence of Type A behavior (assessed by Rosenman's structured interview) between 109 untreated hypertensive subjects and 109 age-, sex-, ethnic-, and occupation matched normotensive subjects. Hypertension status was based on five repeated assessments over a 5-month period. Results indicated that Type A behavior is more prevalent in untreated, mildly hypertensive employed individuals than occupationally matched normotensive subjects. Type A component analysis confirmed the importance of hostility and certain vigorous voice stylistics in predicting cardiovascular conditions. These findings, taken together with the evidence linking Type A behavior with high cholesterol and cigarette smoking, further support the view that this behavior pattern is associated with increased risk of coronary heart disease. PMID- 1860715 TI - Nitroprusside in preeclampsia. Circulatory distress and paradoxical bradycardia. AB - In severe preeclampsia, short-term peripartum management of hypertension with hydralazine is complicated by relatively prolonged hypotensive episodes, resulting in fetal distress. We hypothesized that nitroprusside's rapid onset and brief antihypertensive action would permit more controlled blood pressure reduction. Nitroprusside was infused into 10 invasively monitored subjects until mean arterial pressure either 1) was gradually reduced 10-20% or 2) fell abruptly. Subjects fell into two groups, defined by whether the hypotensive effect of nitroprusside was accompanied by a fall in heart rate (group A, n = 8) or a rise (group B, n = 2). Group B showed the expected sinoaortic baroreceptor reflex elevations in heart rate (+17 +/- 6 beats/min) in response to moderate falls in mean arterial pressure (-32 +/- 9 mm Hg) elicited by moderate doses (1.03 +/- 0.23 micrograms/kg/min). However in group A, steep reductions in mean arterial pressure (-75 +/- 22 mm Hg, p less than 0.0001), significantly greater than in group B (p less than 0.05), occurred at much lower doses (0.35 +/- 0.23 micrograms/kg/min; p less than 0.05) and were accompanied by falls in heart rate (-21 +/- 7 beats/min). The apparently paradoxical falls in heart rate and extreme hypotensive responses in group A indicate severe circulatory compromise, corresponding to the cardiac and vasomotor depression that characterizes severe hemorrhage and other forms of acute/severe hypovolemic hypotension. This hemodynamic pattern represents a cardiopulmonary baroreceptor reflex presumably related to the Bezold-Jarisch reflex. The appearance of this pattern in the present study probably reflects the imposition of nitroprusside's prominent venous dilator action on the relatively reduced blood volume that generally characterizes severe preeclampsia. PMID- 1860716 TI - Polyamines, vascular smooth muscle, and deoxycorticosterone acetate-salt hypertension. AB - This study was performed to determine if an alteration in vascular polyamine contents is associated with the development of deoxycorticosterone acetate-salt hypertension. The effects of chronic administration of alpha difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase and thus polyamine biosynthesis, on vascular polyamine contents, structure, and function as well as the development of hypertension was studied. Control and deoxycorticosterone acetate-salt rats received either tap water or a drinking solution containing alpha-difluoromethylornithine for 6 weeks, during which period systolic blood pressures were recorded. Vascular reactivity studies were performed on rings of aorta and tail artery. Medial thickness, vessel weight, and vascular polyamine contents were also assessed in these arteries. alpha-difluoromethylornithine treatment had no significant effect on either systolic blood pressure or vascular structure, function, and polyamine contents of control animals. The elevation in blood pressure and the increase in medial thickness, ring weight, and vascular polyamine contents as well as altered vascular reactivity observed in deoxycorticosterone acetate-salt rats was significantly attenuated by alpha-difluoromethylornithine treatment. These results are the first to demonstrate that vascular polyamine contents are elevated in the deoxycorticosterone acetate-salt rat and that chronic alpha difluoromethylornithine treatment prevents the rise in vascular polyamines as well as the elevation in blood pressure and attendant changes in the vasculature. Thus, the increase in vascular polyamines may comprise a critical link between the initiating stimuli and the alterations in vascular structure and function implicated in the pathogenesis of deoxycorticosterone acetate-salt hypertension. PMID- 1860717 TI - Heterogeneity of renin alleles in outbred Dahl salt-sensitive (Brookhaven) rats. AB - Selectively outbred Dahl salt-sensitive (DS) and salt-resistant (DR) rats were compared with the inbred Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats developed from the original Brookhaven stocks by J.P. Rapp. The animals were evaluated for genotype at the renin locus. The inbred strains are uniformly homozygous for their respective alleles, s in SS/Jr and r in SR/Jr. DR rats were also uniformly homozygous for the r renin allele. In DS rats, however, three renin alleles were segregating. In addition to the s and r alleles, a third allele, designated the z allele, was found. The gene frequencies in DS rats were s = 0.690, r = 0.284, and z = 0.026. Continued use of DS and DR rats in most experimental work is inappropriate because of genetic heterogeneity in the DS stock. PMID- 1860719 TI - The global challenge of hepatitis B: implications for dentistry. AB - Hepatitis B remains a serious threat to non-immune members of the dental team. Dental personnel who are hepatitis B virus (HBV) carriers, many of whom may not be aware of their status, are also at risk of superinfection with hepatitis delta virus. It is hoped that this paper will assist dentists to understand better their role in preventing HBV infection and for dental staff to understand why acceptance of vaccine is so important to them, their families and their patients. PMID- 1860718 TI - Plasma immunoreactive endothelin-1 in experimental malignant hypertension. AB - We measured plasma concentrations of immunoreactive endothelin-1 (irET-1) in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in malignant hypertension caused by deoxycorticosterone acetate (DOCA)-salt administration in SHR. We also measured concentrations of this peptide in another model of malignant hypertension, the two-kidney, one clip (2K1C) renovascular hypertensive rats chronically given caffeine. Plasma irET-1 concentrations in young (6-week-old) and mature (18-week-old) SHR did not differ from those of age matched Wistar-Kyoto (WKY) rats. Four weeks of treatment with DOCA-salt increased blood pressure, blood urea nitrogen, serum creatinine, and plasma irET-1 in SHR but not in WKY rats. Eight weeks of DOCA-salt treatment further increased these values in SHR. Plasma irET-1 concentrations were not increased in the 2K1C rats. Six weeks of caffeine administration increased blood pressure, blood urea nitrogen, serum creatinine, plasma renin activity, and plasma irET-1 in the 2K1C rats but not in the sham-operated rats. High-performance liquid chromatographic profiles of plasma extracts pooled from these rats with malignant hypertension showed that a major component of irET-1 eluted in the position of synthetic ET-1 (1-21). Furthermore, acute hypertension induced by angiotensin II or phenylephrine did not affect the plasma irET-1 concentration in rats. The results suggested that the plasma ET-1 concentration is increased in rat models of malignant hypertension and that the high blood pressure itself is not the main factor involved in the increase of plasma ET-1. PMID- 1860720 TI - Dental status of children in a primary and secondary school in rural Zambia. AB - This study reports the findings of a survey carried out in Zambia by a UK charity. 'Project Teeth Relief', which aims to provide basic pain relief and dental health education to the rural areas of Zambia. The survey investigated the dental health status of schoolchildren from two rural schools: 354 pupils aged 13 22 years from a secondary school and 121 pupils aged 7-18 years from a primary school. The results show a high level of dental disease in both samples. The results are discussed in relation to the differences between the two schools and to the changes in the social and economic climate in Zambia. PMID- 1860722 TI - Dental claims in the Swedish Patient Insurance Scheme. AB - The Swedish Patient Insurance Scheme covers treatment injuries and guarantees the replacement of failed removable prostheses for 1 year and fixed prostheses for 2 years after fitting. In this paper, 573 dental cases are analysed for a 3-month period in 1986, during which crowns and bridges formed the vast majority of failed treatments that were reported. PMID- 1860721 TI - Osseointegrated implants in the oral habilitation of a boy with ectodermal dysplasia: a case report. AB - The most characteristic oral feature in ectodermal dysplasia is hypodontia. Children and adolescents suffering from ectodermal dysplasia often need extensive and complicated prosthetic treatment. The development of techniques for osseointegrated implants offers new possibilities for the oral habilitation of these children. This paper describes the oral habilitation of a boy with severe ectodermal dysplasia and where Branemark osseointegrated implants have been used as part of the treatment. The patient was seen at the dental department at the age of 1.5 years. Two conically-shaped upper incisors were at that time the only teeth that had erupted. The treatment was planned in a multidisciplinary odontological group involving paediatric dentistry, orthodontics, prosthodontics, oral surgery and maxillofacial radiology. At the age of 3 years it was verified that the boy had four primary teeth (53, 51, 61, 63) and four permanent teeth (16, 11, 21, 26). There were no teeth in the lower jaw. The alveolar ridges in the edentulous areas were low or missing. During the period 3-6 years of age the boy used an upper partial denture adapted to allow the mesial drift of the 16 and 26 teeth. At the age of 6 years, two Branemark implants were inserted in the lower front-cuspid region. A specially designed overdenture for the lower jaw was constructed. The overdenture was retained in contact with the male attachments by two cuffs of heat-polymerized resilient silicone. Over the next 4 years the dentures were modified due to the eruption of permanent teeth and growth. However, only minor corrections were necessary concerning the retention system of the lower denture. The implants are well osseointegrated and stable and allow the boy to use a lower denture without any complications. PMID- 1860723 TI - Role of toothpastes in the cleaning of teeth. AB - Toothpastes have improved significantly over the last 2000 years to the point where they are very proficient in their cleaning attributes. However, research continues, so further improvement may still be possible. PMID- 1860724 TI - Clinical effect and mechanism of cariostatic action of fluoride-containing toothpastes: a review. AB - Caries reduction has been observed in certain parts of the western world. The reduction coincides with the timing of the introduction of fluoride-containing toothpastes and no other factors can explain the caries reduction. It is possible that improved oral hygiene and use of fluoride have a synergistic effect. PMID- 1860725 TI - Current status of the use of ultrasound in endodontics. AB - Although endosonics has received much attention in the literature, it is not clear whether it is recommended. This review discusses the types of endosonic unit available, ultrasonic phenomena such as cavitation and acoustic streaming, irrigation, cutting dentine, and clinical techniques for cleaning and shaping. The more recent evidence suggests that endosonics provides an efficient method of debridement providing sodium hypochlorite is used, but is less efficient at shaping the walls of the canals. New methods of filing have been introduced by the manufacturers but they have not taken into account the most recent research; for this reason an alternative approach is described. PMID- 1860726 TI - Protein kinase C activity as marker for colorectal cancer. AB - Protein kinase C (PKC) activity was measured in normal-appearing colonic mucosa from patients undergoing colonic resection. Comparisons were made between cases with and without colorectal cancers. PKC activity in cytosolic and particulate fractions was significantly reduced in patients with colorectal cancer: 40 +/- 9 and 114 +/- 29 (pmol/min/mg) respectively, compared with patients without cancer; 129 +/- 11 and 250 +/- 38 (pmol/min/mg) (p less than 0.05). Normal-appearing colonic mucosa in patients with cancer showed significantly decreased total PKC activities in the cytosolic and particulate fractions compared with those in patients without cancer (10 +/- 1 and 20 +/- 3 vs. 30 +/- 2 and 33 +/- 6) (pmol/min/g tissue) (p less than 0.05). The cellular distribution (% particulate fraction) of PKC activity in normal-appearing mucosa in patients with cancer (64%) was higher than in patients without cancer (49%) (p less than 0.05). OUr data suggest that PKC activity may be used as a biological marker of risk of developing colorectal cancer or risk of bearing an asymptomatic tumor. PMID- 1860727 TI - Early-age body size, adult weight gain and endometrial cancer risk. AB - To further characterize the association of obesity and endometrial cancer, in particular with regard to the role of early-age obesity and adult weight gain, the authors assembled by computer linkage a population-based historical cohort of 30,266 women born between 1913 and 1932, for whom weight and height had been recorded in 1942-43 and 1972. Linkage of this cohort to the Hawaii Tumor Registry resulted in the identification of 214 (mainly post-menopausal) incident cases of endometrial cancer for 1972-1986. An average of 37 cancer-free controls were matched to each case on month and year of birth and ethnicity. A case-control analysis, conducted in each 5-year birth cohort, revealed no clear association of endometrial cancer with weight, height or body mass at ages 10 to 29 years. However, positive associations with adult body weight and gain in body mass since 1942 were observed for women diagnosed at age 60 or older. This association with obesity was strongest in women whose body mass was below the median in 1942 and equal to or above the median in 1972. No association with body size was detected in women diagnosed before age 60. Parity, age at first birth and socioeconomic indicators for 1942 and 1972 did not confound the analysis. These findings suggest that obesity affects the late stages of endometrial carcinogenesis, and the possibility that one or more determinants of weight gain may be independently associated with endometrial cancer risk. PMID- 1860728 TI - Alcohol consumption and risk of breast cancer. AB - In a national case-control study, 891 New Zealand women aged 25 to 54 with newly diagnosed breast cancer were compared with 1,864 control subjects selected at random from the electoral rolls. The relative risk of breast cancer for current drinkers of alcohol, compared with women who had never drunk alcohol, was 1.0 (95% confidence interval 0.64 to 1.7). For ex-drinkers the relative risk was 1.3 (95% confidence interval 0.74 to 2.5). Women drinking up to 14 drinks per week had no increase in risk, while the relative risk in those consuming more than 14 drinks per week was 1.8 (95% confidence interval 0.87 to 3.8). There was no evidence of effect modification by age at diagnosis, menopausal status, body mass index, or any of the other variables examined. While these results provide little support for the hypothesis that moderate alcohol consumption increases the risk of breast cancer, they are not inconsistent with the weak associations that have been found in many other studies. Possible explanations for such a relationship are considered. PMID- 1860730 TI - Occupation and risk of Hodgkin's disease in north-east Italy. AB - The relationship between occupation and exposure to several occupational agents and Hodgkin's disease (HD) was investigated in a case-control study of 152 cases and 613 controls with acute diseases admitted to all hospitals in Pordenone province, north-east Italy. Among cases, there was a significant excess of individuals occupied in agriculture (odds ratio, OR for greater than 10 years = 2.2, 95% confidence interval, CI:1.3-3.7), who were exposed to livestock and meat processing (OR = 3.4, 95% CI:1.7-6.6), herbicides and pesticides (OR = 3.2, 95% CI:1.6-6.5). When the relationship between agriculture and specific exposures was assessed, it appeared that contact with some still unidentified animal-related agent involved in livestock farming and meat processing may be at least as important in determining HD risk as exposure to herbicides and pesticides and, probably, more important than occupation in agriculture per se. PMID- 1860729 TI - Spontaneous and induced abortions and risk of breast cancer. AB - The relationship between spontaneous or induced abortion and the risk of breast cancer was analyzed in a case-control study conducted in the greater Milan area on 2,394 cases of breast cancer and 2,218 controls in hospital for a spectrum of acute conditions, not gynecological, hormonal or neoplastic. No consistent relationship emerged between spontaneous or induced abortion and breast cancer: compared with women reporting no abortions (spontaneous or induced), the multivariate relative risk (RR) was 1.0 (95% confidence interval, CI, 0.9 to 1.2) in those reporting one abortion and 0.9 (95% CI 0.7 to 1.0) in those reporting two or more. This lack of association was consistent in strata of age and parity, including younger women. We further analyzed the risk of breast cancer associated with an abortion before and after full-term pregnancy. Compared with parous women reporting no induced or spontaneous abortions, those who had an abortion before their first full-term pregnancy had about a 20% higher risk of breast cancer. This finding, however, was not statistically significant (RR 1.2, 95% CI 0.9 to 1.7). No increased risk was observed in women who had had a first abortion after a full-term pregnancy (RR 0.9, 95% CI 0.8 to 1.0). This study does not support the hypothesis that spontaneous or induced abortion appreciably influences subsequent breast-cancer risk. PMID- 1860731 TI - The EORTC Melanoma Group exchange program: evaluation of a multicenter monoclonal antibody study. AB - In the framework of the European Organisation for Research and Treatment of Cancer (EORTC), the Immunology and Pathology Subgroups of the Malignant Melanoma Cooperative Group undertook a large multicenter monoclonal antibody (MAb) study. Fourteen laboratories from 7 European countries tested a panel of 23 MAbs for immunohistological staining reactivity for malignant and non-malignant lesions involving the melanocytic lineage. A standardized immunoperoxidase procedure was used and the results were evaluated using a standard protocol and data evaluation form developed in collaboration with the EORTC Data Center. According to this analysis, the antibodies in the panel could be classified into 3 main groups. The first group of MAbs includes those antibodies which stained the majority (greater than 80%) of all primary tumors, irrespective of their Breslow thickness and the majority of metastatic lesions. In addition, these MAbs stained a high percentage of cells within a given lesion. Several antibodies of Group I were likewise reactive with the majority of naevoblasts and with normal melanocytes. The second group of MAbs included antibodies reacting only with a limited number of primary melanomas and metastatic lesions. Antibodies of Group II reacted only weakly, if at all, with normal melanocytes or naevocytes. The percentage of cells within a malignant lesion stained by these MAbs was always rather low. The MAb group III detected surface structures whose expression appeared to be related to tumor progression; they did not react or reacted only weakly with naevi, and they all reacted with a small number of early primary melanomas (less than 0.75 mm). The number of lesions stained increased with increasing Breslow thickness. Our study suggests that the application of a panel of well defined MAbs might be of diagnostic and prognostic value in evaluating malignant melanoma. PMID- 1860732 TI - Monoclonal antibodies against Gal alpha 1-4Gal beta 1-4Glc (Pk, CD77) produced with a synthetic glycoconjugate as immunogen: reactivity with carbohydrates, with fresh frozen human tissues and hematopoietic tumors. AB - The purpose of this study was to isolate mouse monoclonal antibodies (MAbs) recognizing Gal alpha 1-4Gal beta 1-4Glc (Pk, CD77), which has been described as a Burkitt's-lymphoma-associated antigen. Three IgGI MAbs reactive with Pk were developed using a synthetic glycoconjugate as immunogen and a filter immunoplaque screening assay. One MAb (PK67) was characterized by immuno-thin-layer chromatography, ELISA and competition assays using neutral glycolipids from various sources and a variety of carbohydrates and glycoproteins. Epitope analysis showed that all 3 carbohydrates moieties are required in PK67 binding. No cross-reactivity was observed with closely related carbohydrate structures, with the exception of Gal alpha 1-4Gal beta 1-4GlcNAc. However, the reactivity with this structure was several orders of magnitude lower than with Pk. Immunohistochemical analysis of fresh-frozen tissue specimens showed that Gb3 is widely expressed: prominent staining was observed in many normal tissues, e.g., kidney and gastric tissue and on capillary endothelial cells. In lymph nodes, very weak staining of a few B cells was observed. Flow cytometric analysis of hematopoietic neoplasms showed Gb3 expression on B-cell neoplasms, particularly those with committed B-cell phenotype indicating that, in addition to earlier reports of Gb3 expression on Burkitt's lymphoma, Gb3 is present on other committed B-cell neoplasms. PMID- 1860733 TI - Glutathione and cellular response of ACNU-resistant rat glioma sublines to drugs and radiation. AB - Three ACNU-resistant sublines (R1, R3 and R12) from rat glioma 9L cells showed cross-resistance to vinblastine, adriamycin, and VP-16. Among these, the R3 subline also acquired radioresistance under aerobic conditions. Total glutathione levels in these sublines were elevated 2- to 3-fold. Treatment of the cells with BSO, a specific inhibitor of GSH synthesis, resulted in decreased intracellular total glutathione levels in all 4 cell lines to about 10% of control levels. However, sensitivity to radiation or to chemicals did not change accordingly. Treatment of 9L cells with OTZ, a precursor of cysteine, resulted in a rise in intracellular GSH levels but it did not correlate with sensitivity to X-ray or to ACNU. These results suggest that, in terms of cellular sensitivity to radiation or ACNU, total glutathione level alone cannot serve as a predictive indicator. PMID- 1860734 TI - Effect on N1,N14-bis-(ethyl)-homospermine (BE-4-4-4) on the growth of U-251 MG and SF-188 human brain tumor cells. AB - We studied the effects of the spermine analogue N1,N14-bis-(ethyl)-homospermine (BE-4-4-4) on growth, survival and polyamine levels in cultured U-251 MG and SF 188 human brain tumor cells. After 48 hr of treatment at concentrations of 1 microM or higher, BE-4-4-4 accumulated in cells with a concomitant decrease in intracellular putrescine, spermidine and spermine concentrations. Growth inhibition by 10 microM BE-4-4-4 began at 6 hr and peaked between 16 and 24 hr. The analogue was also increasingly cytotoxic with doses between 1 and 10 microM and with treatment times between 16 and 48 hr. Polyamines added 1 day after BE-4 4-4 lowered the intracellular concentrations of the analogue but did not reverse its growth-inhibitory activity. When added simultaneously with the analogue, however, polyamines caused a decrease in analogue concentration that was accompanied by a block to the growth inhibition. BE-4-4-4 has a higher affinity for DNA than spermine has, but is less able to aggregate DNA. Its growth inhibitory and cytotoxic effects support our hypothesis that polyamine analogues that enter cells and replace natural polyamines at DNA binding sites, without fulfilling their biologic functions, should act as antiproliferative agents. PMID- 1860736 TI - A recombinant vaccinia virus expressing human carcinoembryonic antigen (CEA). AB - Carcinoembryonic antigen (CEA) is a 180-kDa glycoprotein expressed on most gastrointestinal carcinomas. A 2.4-kb cDNA clone, containing the complete coding sequence, was isolated from a human colon tumor cell library and inserted into a vaccinia virus genome. This newly developed construct was characterized by Southern blotting, DNA hybridization studies, and polymerase chain reaction analysis. The CEA gene was stably integrated into the vaccinia virus thymidine kinase gene. The recombinant was efficiently replicated upon serial passages in cell cultures and in animals. The recombinant virus expresses on the surface of infected cells a protein product recognized by a monoclonal antibody (COL-I) directed against CEA. Immunization of mice with the vaccinia construct elicited a humoral immune response against CEA. Pilot studies also showed that administration of the recombinant CEA vaccinia construct was able to greatly reduce the growth in mice of a syngeneic murine colon adenocarcinoma which had been transduced with the human CEA gene. The use of this new recombinant CEA vaccinia construct may thus provide an approach in the specific active immunotherapy of human GI cancer and other CEA expressing carcinoma types. PMID- 1860735 TI - Natural killer-cell activity under conditions reflective of tumor micro environment. AB - Natural-killer(NK) activity was examined in the presence of low oxygen tension, low glucose concentration and acidic pH, to determine whether physical conditions present in the tumor micro-environment could play a role in down-regulating cytolytic activity of tumor-infiltrating lymphocytes with NK phenotype. Anoxia (0% O2), but not hypoxia (1% O2), significantly reduced NK activity, as did acidic pH (6.4 or 6.7). Low glucose concentration (6 mg/dl) did not impair NK activity. Combinations of either moderate (1% O2, 26 mg/dl glucose, pH 6.7) or extreme (0% O2, 6 mg/dl glucose, pH 6.4) alteration of physical conditions significantly reduced NK activity. This study indicates that the physico-chemical conditions present within solid tumors are capable of down-regulating NK activity. PMID- 1860737 TI - Induction of mouse mammary tumours in a transplantation system by the sequential introduction of the myc and ras oncogenes. AB - A novel helper-free defective retrovirus containing the v-Ha-ras oncogene has been constructed and used to introduce the gene into primary mouse mammary epithelial cells already containing the v-myc oncogene. Transplantation of such doubly altered cells into cleared mammary fat pads led to the formation of mammary tumors within 6 to 8 weeks of transplantation. In a separate experiment, both oncogenes were simultaneously introduced to normal epithelium and once again tumours were formed. Neither oncogene alone gave a significant rate of tumour formation, although myc alone gave a reproducible hyperplasia as previously reported and ras alone gave occasional dysplastic or alveolar lesions. The results presented here demonstrate the progression of a normal cell through a hyperplastic intermediate to a tumour-forming cell in a versatile in vivo transplantation model. PMID- 1860738 TI - The interrelationship between the anti-mitotic action of the somatostatin analog octreotide and that of cytostatic drugs and suramin. AB - In the present study we used the model of cultured somatostatin-receptor-positive prolactin (PRL)-secreting rat pituitary tumor cells to investigate the possible interrelationships between the anti-mitotic and hormone-release-inhibitory effects of the somatostatin analog octreotide (SMS 201-955) and the effects of vincristine, methotrexate, fluouracil and suramin. Dose-dependent inhibitory effects of all compounds were shown both on the DNA content and on PRL release. Octreotide and these cytostatic compounds were slightly additive in their anti proliferative and anti-secretory effects. The somatostatin analog did not alter drug sensitivity in these tumor cells, however. The data obtained in this tumor model suggest that octreotide can be effectively administered in combination with cytostatic drugs and/or suramin. PMID- 1860739 TI - Effect of caloric deficit and dietary manipulation on aerobic and anaerobic exercise. AB - Twelve competitive wrestlers restricted their caloric intake (92 kJ/kg FFW/day) for 7 days, using a high (HC) or normal (NC) carbohydrate diet to determine the acute effect of caloric deficiency on aerobic and anaerobic exercise performance as well as growth hormone (hGH) and insulin-like growth factor 1 (IGF-1) levels. The subjects were tested while on a eucaloric diet and at the end of the dietary restriction. Neither the dietary restriction nor composition had an effect on the ability to complete an 8-minute run at 85% of maximal capacity, but both produced an increased fat utilization during the run. The responses to the Wingate Anaerobic Test indicated that the NC group had a significant reduction in total and mean power output (-7% & -6%, respectively; p less than 0.05), whereas the HC group maintained all power measures. The caloric restriction, regardless of dietary composition, increased the exercise hGH response more for the NC group than the HC group (p less than 0.05). IGF-1 levels were significantly lowered by the diet, but the diet composition had no effect. These results indicate that even during caloric restriction, a high carbohydrate diet better maintains anerobic exercise performance. Furthermore, the composition of the diet appears to have no effect on the resting hGH and IGF-1 responses to caloric deficits. However, carbohydrate composition may have an effect on the gGH response to exercise. PMID- 1860740 TI - Iron status of active women and the effect of running a marathon on bowel function and gastrointestinal blood loss. AB - This study compared the bowel function, fecal hemoglobin (Hb) loss, iron status and diets of 36 women of varying activity levels. In addition, we examined the effect of a marathon race on bowel function and fecal Hb loss in 15 of these women. The subjects were divided into 4 groups based on estimated daily exercise energy expenditure: Group A) less than 400 kcal/d (less than 1674 kJ/d); Group B) 400-599 kcal/d (1674-2507 kJ/d); Group C) 600-800 kcal/d (2511-3348 kJ/d); and Group D) greater than 800 kcal/d (greater than 3348 kJ/d). There were no differences in hematological and iron indexes among the 4 groups. Mean daily stool wet weights and individual stool weights were greater for groups B and D as compared to group A. However, transit time and frequency of defecation were not different. Daily fecal Hb losses (mg/day) were greater in groups B, C, and D as compared to A, but there was no difference in fecal Hb concentrations (mg/g feces) among the groups. Dietary intakes of energy, protein, fat and fiber were similar for all groups. Ascorbic acid and iron intakes from food significantly increased with increased estimated daily energy expenditure. Total intakes of ascorbic acid and iron, including oral supplements, were not different among the groups. Marathon racing resulted in a 21% increase in mean transit time, a 27% decrease in daily stool weight and 21% lower frequency of defecation. Fecal Hb concentrations and daily Hb losses before and after the race were not significantly different, despite an increased daily Hb loss in 10 of the 15 runners after the race.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860742 TI - Effect of prolonged exercise on insulin level in the portal and peripheral venous circulation in rats. AB - The purpose of the present study was to compare the plasma insulin levels in portal and peripheral veins in rats submitted to a prolonged exercise to exhaustion (mean +/- SE: 67 +/- 7 min). Plasma insulin levels were reduced significantly (p less than 0.01) during exercise in both the portal and peripheral venous circulation. The reduction was, however, more pronounced in the portal than in the peripheral vein (mean: -113 vs -64 and -162 vs -88 pmol.l-1 after 30 and 45 min of exercise, respectively), indicating that exercise reduced not only insulin secretion but also its removal. Accordingly, no significant differences were found for the portal/peripheral ratio of insulin at rest and during the first 45 min of exercise (1.86 +/- 0.2, 1.76 +/- 0.1, and 1.57 +/- 0.2 at rest, and after 30 and 45 min of exercise, respectively). This suggests that insulin removal during exercise is regulated in proportion to portal insulin concentrations. PMID- 1860741 TI - Carbohydrate feeding before exercise: effect of glycemic index. AB - Low glycemic index (GI) foods may confer an advantage when eaten before prolonged strenuous exercise by providing a slow-release source of glucose to the blood without an accompanying insulin surge. To test this hypothesis, eight trained cyclists pedalled to exhaustion one hour after ingestion of equal carbohydrate portions of four test meals: lentils, a low GI food (LGI); potato, a high GI food (HGI), and glucose and water. Plasma glucose and insulin levels were lower after LGI than after HGI from 30 to 60 min after ingestion (p less than 0.05). Plasma free fatty acid (FFA) levels were highest after water (p less than 0.05) followed by LGI and then glucose and HGI. From 45 to 60 min after ingestion, plasma lactate was higher in the HGI trial than in the LGI trial (p less than 0.05) and remained higher throughout the period of exercise. The rank order from lowest to highest for total carbohydrate oxidation during exercise was water, lentils, glucose and potato. Endurance time was 20 min longer after LGI than after HGI (p less than 0.05). These findings suggest that a low GI pre-game meal may prolong endurance during strenuous exercise by inducing less post-prandial hyperglycemia and hyperinsulinemia, lower levels of plasma lactate before and during exercise, and by maintaining plasma glucose and FFA at higher levels during critical periods of exercise. PMID- 1860743 TI - Incremental test protocol, recovery mode and the individual anaerobic threshold. AB - The individual anaerobic threshold (IAT) is defined as the highest metabolic rate at which blood lactate (LA) concentrations are maintained at a steady-state during prolonged exercise. The purpose of this study was to compare the effects of active and passive recovery on the determination of IAT following both a submaximal or maximal incremental exercise test. Seven males (VO2max = 57.6 +/- 5.8 ml.kg-1.min -1) did two submaximal, incremental cycle exercise tests (30 W and 4 min per step) and two maximal incremental tests. Blood was sampled repeatedly during exercise and for 12 min during the subsequent recovery period, which was passive for one submaximal and one maximal test and active (approximately 35% VO2max) during the other tests. An IAT metabolic rate and power output were calculated for the submax-passive (IATsp, LA = 1.85 +/- 0.42 mmol.l-1), max-passive (IATmp, LA = 3.41 +/- 1.14 mmol.l-1), submax-active (IATsa, LA = 2.13 +/- 0.45 mmol.l-1) and max-active (IATma, LA = 3.44 +/- 0.73 mmol.l-1) protocols. At weekly intervals, the subjects exercised for 30 min at one of the four IAT metabolic rates. Active recovery did not affect the calculation of IAT, but following the maximal incremental tests, IAT occurred at a higher (p less than 0.05) power output, absolute VO2 and %VO2max (71% VO2max) compared with the IAT determined with the submaximal incremental tests (61% VO2max).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860744 TI - Physiological characteristics of elite judo athletes. AB - In order to provide some understanding of the physiological capacities underlying successful judo performance, representative values for a variety of physiological variables were determined in nationally ranked male (n = 18) and female (n = 9) judo athletes. Body composition, aerobic capacity, isokinetic elbow and knee flexor and extensor strength, and muscle fiber size and composition of the vastus lateralis were examined. Comparisons across weight divisions indicate that the values of many characteristics varied as a function of size. As weight division increased, relative VO2 decreased (r = -0.53 and -0.63 for males and females, respectively), % body fat increased (r = 0.64, 0.72), and the cross sectional areas of Type I (r = 0.55, 0.77) and Type IIA (r = 0.47, = 0.76) muscle fibers increased. Among females in particular, athletes in the higher weight divisions were stronger relative to LBM than those in the lower division. These results indicate that the physiological profiles of lower and upper weight division elite judo players differ markedly. It is suggested that the factors responsible for success may be specific to each weight division and may represent a compromise between making weight and maximizing physiological capacities and performance. PMID- 1860745 TI - Effect of muscular activity on the turnover rate of actin and myosin heavy and light chains in different types of skeletal muscle. AB - In endurance-trained rats the myosin HC have a more rapid turnover rate than in control animals in all three types of skeletal muscle fibres, but in sprint trained rats only in fast-glycolytic and fast-oxidative-glycolytic fibres. A comparison of the actin turnover rate in sprint- and endurance-trained animals shows that in both groups there are more rapid turnover rates in all types of muscle fibres in comparison with control rats. During long-lasting exhaustive exercise the turnover rate of myosin HC decreases. Twelve hours after exercise, myosin LC 2 and 3, and actin have a more rapid turnover than in control rats. Changes in the turnover rate of muscle contractile proteins during exercise and the recovery period after exercise reflect the functional conditions of the contractile apparatus in different types of skeletal muscle fibres and have a physiological significance. PMID- 1860746 TI - Force-velocity relationship of human elbow flexors in voluntary isotonic contraction under heavy loads. AB - The force-velocity relationships of the human elbow flexors as one muscle in maximal voluntary contraction were determined using isotonic lever systems for seven men (19-38 yrs). The external loads used for the contraction weighed 0%, 20%, 40% 60%, 80% and 90% of maximum voluntary isometric force (Fo). The force and velocity were determined at an elbow angle of 90 degrees. The effect of the inertia of the forearm on the force was corrected using the angular acceleration of the forearm during an elbow flexion. The effect of muscular fatigue on the velocity during an elbow flexion was minimized by adjusting the initial elbow angle at the onset of the elbow flexion to the size of the load and reducing the time duration of the elbow flexion with a heavy load. Hill equation fitted fairly well to the force-velocity data observed in the experiments up to 90% Fo. The maximum isometric force predicted using Hill equation was larger by 6% (mean) than that observed in the experiments. PMID- 1860747 TI - Low vertebral bone density values in young non-elite female runners. AB - Thirty-five female runners (26.6 +/- 0.9 years, range 17-35) were scheduled for bone mineral density evaluation, using quantitative computed tomography of the lumbar spine. In 17 women with oligo-amenorrhea, vertebral bone mineral density was under the normal range (defined from a control group of 46 sedentary healthy females in the same age range), while it was within the normal range in all runners with regular menses (n = 18). When age classes were considered, all runners aged 17-21 (11/11) were found to have oligo-amenorrhea and low bone mineral density values, the difference in mineral density with the controls of the same age quartile being highly significant (p less than 0.001). Runners from the two youngest age classes (17-21 and 22-26) had started training early after menarche (0.9 +/- 0.6 and 2.5 +/- 1.6 years, respectively). These results show that very young female runners with oligo-amenorrhea may have impressively low bone mineral density values. The possibility that early onset of training, close to menarcheal age, might be a risk factor for low mineral density, deserves further investigation. PMID- 1860748 TI - Influence of aging, training and acute physical exercise on plasma glutathione and lipid peroxides in man. AB - In trained (long-distance runners) and untrained volunteers aged 22 to 57 years, basal plasma glutathione (GSH) concentration decreased significantly with increasing age. In most age groups basal GSH concentration of oxidized glutathione (GSSG) and lipid peroxides (LPO) was not influenced either by age or by training. Following acute physical exercise (bicycle ergometric test), which was maximal for each person and thus different in trained and untrained persons, plasma GSH, GSSG, and LPO concentrations were not changed at all in untrained volunteers. In trained persons, however, GSH concentration was significantly decreased by about 30%. Surprisingly, we observed a decrease in plasma LPO content by about 40%. GSSG content was not altered. The comparison with some physical-physiological parameters indicates that the changes in GSH and LPO concentrations depend on the extent of acute physical exercise rather than on previous training. Alterations of GSH and LPO in plasma could be of physiologic significance. PMID- 1860750 TI - Advantages of electrocardiographic monitoring in top level athletes. AB - We used continuous electrocardiographic monitoring according to Holter's method for a tentative evaluation of the prognostic value of the main electrocardiographic peculiarities of the "athlete's heart". Five hundred and eighty-seven Holter recordings were performed in 164 top athletes divided into three groups: dynamic, static and mixed. Selection criteria were either clinical or electrical (resting-ECG). The prognostic value of arrhythmia is variable: unworrying junctional rhythm (JR) and auriculo-ventricular blocks (AVB) that disappeared under strain, which in our study interested mostly the dynamic group. No pejorative prognostic criteria were found related to supraventricular premature beats (SVPB). Ventricular premature beats (VPB) of recent occurrence were predominantly found, in our study, in the static athletes; their occurrence was not always accounted for and their prognosis, at least as regards sports, was uncertain. Holters repeated throughout the sports season made it possible to establish a relationship between some peculiarities and the training intensiveness: auriculo-ventricular block and junction rhythm culminated during intensive periods. Unusual sinus tachycardia would be indicative of over training. PMID- 1860749 TI - Endogenous anabolic hormonal and growth factor responses to heavy resistance exercise in males and females. AB - To examine endogenous anabolic hormonal responses to two different types of heavy resistance exercise protocols (HREPs), eight male and eight female subjects performed two randomly assigned protocols (i.e. P-1 and P-2) on separate days. Each protocol consisted of eight identically ordered exercises carefully designed to control for load, rest period length, and total work (J) effects. P-1 utilized a 5 RM load, 3-min rest periods and had lower total work than P-2. P-2 utilized a 10 RM load, 1-min rest periods and had a higher total work than P-1. Whole blood lactate and serum glucose, human growth hormone (hGH), testosterone (T), and somatomedin-C [SM-C] (i.e. insulin-like growth factor 1, IGF-1) were determined pre-exercise, mid-exercise (i.e. after 4 of the 8 exercises), and at 0, 5, 15, 30, and 60 min post-exercise. Males demonstrated significant (p less than 0.05) increases above rest in serum T values, and all serum concentrations were greater than corresponding female values. Growth hormone increases in both males and females following the P-2 HREP were significantly greater at all time points than corresponding P-1 values. Females exhibited significantly higher pre-exercise hGH levels compared to males. The P-1 exercise protocol did not result in any hGH increases in females. SM-C demonstrated random significant increases above rest in both males and females in response to both HREPs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860751 TI - The relationship of early versus two-minute recovery echocardiographic values following maximal effort resistance exercise. AB - Two-dimensionally directed M-mode echocardiography was used to measure left ventricular systolic function following maximal dynamic resistance exercise (RE). Upright measurements were made from the long axis parasternal view at rest, 20 seconds post-exercise, and two minutes post-exercise. Thirty-two successful studies were recorded from a total of 37 trained and untrained male subjects who were heterogeneous as to mode and level of training. Resistance-trained men averaged 3.8 +/- 2.4 yrs of training for 9.7 +/- 3.0 hr/wk, and endurance-trained men averaged 6.4 +/- 3.9 yr of training at 202.5 +/- 112.6 km/wk of cycling, running, and swimming. The trained men competed at the state or regional level. The RE protocol (knee extensions) was performed as follows: Set 1 (10 s rest) Set 2 (10 s rest) Set 3 60% 1-RM@8 reps 60% 1-RM@8 reps 60% 1-RM to fatigue. The RE protocol produced significant post-exercise reductions in end-systolic diameter (p less than 0.0002) and significant post-exercise increases in fractional shortening (p less than 0.0001) and velocity of circumferential fiber shortening (p less than 0.0002). The inotropic variables were still significantly different at two minutes post-exercise compared to the 20 second measure, suggesting that early recovery is a better approximation of maximal values. Velocity of circumferential fiber shortening at 20 seconds and two minutes was significantly correlated (r = 0.39) and fractional shortening was not (r = 0.34) at these serial measurement times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860752 TI - Getting involved. PMID- 1860753 TI - Which one? PMID- 1860754 TI - Early indicators. PMID- 1860755 TI - How old is old? PMID- 1860756 TI - Is it possible to modulate the growth of the human mandible with a functional appliance? AB - A significant increase in overall mandibular length can be achieved with a functional appliance. However this only appears possible in children with a high tissue-level growth potential and responsiveness as defined by the mandibular subperiosteal ossification rate and alveolar bone turnover rate. PMID- 1860757 TI - Lower crowding. PMID- 1860758 TI - Color mammography. Image generation and receiver operating characteristic evaluation. AB - Color mammography is a technique whereby dual-energy mammographic image data are used to calculate a calcium image; the calcium image is colorized and overlaid onto the conventional (lower energy) gray scale mammogram for radiologist viewing. This technique is presented as a practical way to use the increased calcium sensitivity of dual-energy mammography without requiring an increase in the number of images that the radiologist must read, and without subjecting the radiologist to the unfamiliar appearance of the dual-energy subtracted images. Using straightforward imaging theory, the acquisition techniques for both conventional and dual-energy mammography were optimized, and the optimal technique factors were used to generate a series of computer-simulated mammographic images that were used in a receiver operating characteristic (ROC) comparative study. Ideal observer ROC experiments indicate that (dual-energy) calcium images yield consistently higher sensitivity and specificity to the presence of calcifications, regardless of the amount of tissue "clutter," whereas conventional mammography results show degraded detectability performance as tissue contrast increases. Using human observers viewing simulated images, color mammography delivered greater calcification detectability than conventional mammography. PMID- 1860759 TI - Use of biostereometric analysis as a screen for breast cancer. AB - Biostereometric analysis, a photographic surface imaging technology that is noninvasive, was tested for its effectiveness in selecting breast pathology in a sample of 1000 female subjects, including 80 with cancers, 635 normals, and 285 with benign breast conditions. These individuals were recruited from the population of women undergoing routine mammographic examination. The project was designed specifically to determine whether biostereometric analysis could identify the individuals in the sample with malignant breast disease in the hope of providing information to aid in future development of a breast cancer screening protocol. The overall sensitivity of the method for cancers of all sizes was 76%. Biostereometric analysis was 85% sensitive for selection of cancers in the subjects over 50 years of age, and identified 80% (4 of 5) of the subjects with clinically confirmed breast cancers less than 1 cm in size. The method was 69% specific, but identified benign breast disease in only 51% of cases. PMID- 1860760 TI - Expert learning system network for diagnosis of breast calcifications. AB - Breast calcification diagnosis was studied by using clinical findings and computerized image processing of a mammogram in a network of trained expert learning systems (Outcome Advisor [OA]). The system was tested with records not used for training and performance was compared with radiologist. The network was 72% accurate in classifying clusters of calcifications as malignant or benign over a set of test cases radiologists had considered "hard-to-diagnose calcifications," and referred for biopsy. The radiologists had decided to conduct biopsy by selecting an equal number of positive and negative cases for the test group; thus the radiologists' performance with respect to categories of benign versus malignant was constrained to be 50/50. Statistical analysis shows only a 2% probability that the observed accuracy of 72% was a chance performance in recognizing whether a cluster is benign or malignant. The feasibility of developing a network of OAs for diagnosing breast cancer integrating digital image processing of mammograms is promising. PMID- 1860761 TI - Contrast-enhanced magnetic resonance imaging of hypoperfused myocardium. AB - Contrast-enhanced magnetic resonance (MR) imaging can define myocardial perfusion defects due to acute coronary occlusion. However, since most clinically important diagnostic examinations involve coronary arteries with subtotal stenoses, we investigated the ability of MR imaging with a manganese contrast agent to detect perfusion abnormalities in a canine model of partial coronary artery stenosis. The contrast agent was administered after the creation of a partial coronary artery stenosis with the addition of the coronary vasodilator dipyridamole in six of 12 animals. The hearts were imaged ex situ using gradient reversal and spin echo sequences, and images were analyzed to determine differences in signal intensity between hypoperfused and normally perfused myocardium. Comparison of MR images with regional blood flow and thallium-201 measurements showed good concordance of hypoperfused segments in those animals given dipyridamole, with 75% of the abnormal segments correctly identified. In those animals not given dipyridamole, 48% of segments were correctly identified. Thus, ex vivo MR imaging with a paramagnetic contrast enhancement can be used to detect acute regional myocardial perfusion abnormalities due to severe partial coronary artery stenoses. PMID- 1860762 TI - Percutaneous mechanical thrombolysis. A comparative study of various rotational catheter systems. AB - In vitro fragmentation of thrombi was performed with the Kensey catheter, the Bildsoe catheter, the Gunther aspiration catheter, and two modified aspiration catheters in a model circuit under femoral and pulmonary artery flow conditions. In the femoral artery model all tested catheters worked sufficiently: particles larger than 1000 microns in the effluent comprised only 1.27% +/- 0.46% of the initial thrombus weight. In the treatment of larger thrombi (pulmonary artery model), the action of rotational aspiration devices, and in particular of the Bildsoe catheter, was limited: fibrin filaments winding around the rotating tip led to catheter obstruction. The Kensey catheter yielded best results in the fragmentation of large thrombi. PMID- 1860763 TI - Renal clearance of an ionic high-osmolar and a nonionic low-osmolar contrast medium. AB - One hundred patients with normal serum creatinine concentration underwent intravenous urography with either an ionic high-osmolar (diatrizoate) or a nonionic low-osmolar (iopamidol) contrast medium after randomization. Before injection of the contrast medium, a blood sample was drawn for determinating serum creatinine concentration, and a urine sample for measurement of urine osmolality. Using x-ray fluorescence, the plasma concentration of iodine (contrast medium) was determined on blood samples drawn approximately 3 and 4 hours after injection of the contrast medium. The glomerular filtration rate was calculated by two different formulas: one requiring only a single sample and one requiring at least two samples (standard). There were poor correlations between the standard contrast medium clearance and the serum creatinine concentration, the estimated creatinine clearance (calculated from a nomogram), as well as the urine osmolality. The 3-hour and the 4-hour single-sample values correlated well with the two-sample values for both contrast media. In patients with normal serum creatinine, the glomerular filtration rate determined by measuring the contrast medium concentration in a single plasma sample obtained at 3 hours, is almost identical to the value determined from two samples. Consequently, two samples are unnecessary. PMID- 1860764 TI - Traumatic pneumoperitoneum. Implications of computed tomography diagnosis. AB - Pneumoperitoneum detected on plain radiographs following blunt abdominal trauma is nearly pathognomonic of bowel perforation and usually mandates exploratory laparotomy. To determine the significance of computed tomography (CT)-detected pneumoperitoneum, we reviewed the clinical records and imaging studies of all trauma patients in our hospital over a seven-year period whose abdominal CT scans showed free intraperitoneal gas. Patients who had penetrating injuries or peritoneal lavage prior to CT were excluded. Of the 18 patients who met these inclusion criteria, surgically confirmed bowel injury was found in only four (22%). In the remaining 14 patients, no evidence of gastrointestinal perforation was found by exploratory laparotomy (2 patients), diagnostic peritoneal lavage (4 patients), GI studies and clinical follow-up (6 patients), or clinical follow-up alone (5 patients). Seven patients had a pneumothorax as a possible cause for pneumoperitoneum. Two additional patients were on mechanical ventilation. Unlike pneumoperitoneum seen on plain film, CT-detected pneumoperitoneum is not pathognomonic of bowel perforation. While laparotomy is not mandatory in the non surgically explored patient, close clinical observation is essential, and additional diagnostic tests such as peritoneal lavage or radiographic contrast studies can be beneficial to confirm the absence of intestinal injury. PMID- 1860765 TI - Electrocardiogram changes during intrauterine injection of ionic contrast medium. AB - The effect of intrauterine injection of meglumine-sodium diatrizoate 60% on the electrocardiogram was studied in 28 young, healthy women during routine hysterosalpingography. The most important single finding observed was significant QTc prolongation in 25 (90%) out of the 28 women examined. QTc increased from 417 +/- 18 mseconds to 451 +/- 30 mseconds (P less than .001). This effect disappeared rapidly within 2 to 3 minutes. Saline was injected in ten women prior to contrast medium injection in order to exclude direct mechanical dilatatory effect of the injected material. The QTc did not change significantly after saline (418 +/- 18 mseconds). The mechanism involved in the QTc prolongation is not known. PMID- 1860766 TI - Evacuation proctography in normal volunteers. AB - Constipated patients evaluated by evacuation proctography may be subjected to vigorous medical therapy or surgery, even colectomy, based on radiographic findings that have been called "abnormal" in the literature. Criteria for normal defecography are not uniformly established, nor has correlation of structural or functional findings with symptoms been clearly documented. We prospectively studied 21 asymptomatic volunteers to assess the frequency of findings in a control population, and to establish a quantitative measure of normal rectal emptying. Standard defecography technique demonstrated rectocele, intussusception, pelvic descent, or puborectalis spasm in 14/21 volunteers (67%). The range of rectal emptying was 12.5% to 100%, with four subjects (19%) evacuating less than or equal to 40% of the barium paste. There was no correlation between severity of radiographic findings and degree of evacuation. Defecography results in patients being considered for symptomatic intervention should be interpreted cautiously, given the wide range of normal variation in a control population. PMID- 1860767 TI - Fraud. The journal's role concerning fraudulent research. PMID- 1860768 TI - Clinical experience in the use of photostimulable phosphor radiographic systems. AB - The experience with CR systems gained at the three institutions described in this report demonstrates numerous advantages over the conventional screen-film system. These include: (1) a reduction in the radiation exposure delivered to the patient (25% to 50%); (2) a decrease in the number of repeat examinations needed, especially in portable units where technical difficulties are common with screen film examinations; this is attributable to the linear, wider dynamic range of CR systems compared with screen-film combinations; (3) the capability to archive electronically all images by means of a digital optical storage system; (4) automatic electronic setting of the laser scanner for the latitude and sensitivity on each image; (5) the digital images are available for transmission to all image display workstations on a local or wide-area network; and (6) the ability to adjust interactively the display parameters to best depict images and pathology as well as salvage technically suboptimal examinations. Several disadvantages of CR systems compared with conventional screen-film examinations have also been identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860769 TI - Comprehensive breast cancer detection in an academic environment. PMID- 1860770 TI - Regulation of cutaneous wound healing by growth factors and the microenvironment. PMID- 1860771 TI - Prognosis of abdominal aortic aneurysms: a population-based study. AB - Nevitt, Ballard, and Hallett reviewed the charts of virtually all known cases of abdominal aortic aneurysms in residents of Rochester, Minnesota, from 1951 to 1984. Of 370 patients included in this retrospective study, 181 had at least one ultrasound examination; 103 of these had at least two, and 67 had three. Five patients who had leakage or rupture of their aneurysm within 48 hours of their first ultrasound were excluded. The authors found that the median and mean increase in aneurysm size was 0.21 cm and 0.26 cm per year, respectively. There were no cases of rupture in aneurysms less than 5.0 cm in diameter over the course of the study. Aneurysms which on presentation had a diameter of less than 3.5 cm. had a 0% incidence of rupture at eight years. The risk of eventual rupture, following enlargement, for aneurysms 3.5 to 4.9 cm at first ultrasound, was 5% at nine years. Of aneurysms greater than 5.0 cm at the outset, 25% had ruptured by eight years. No significant data regarding rate of change in size relative to risk of rupture were derived. The authors conclude that the rate of expansion of aneurysms is less than the accepted figure of 0.4 cm per year, and that risk of rupture of aneurysms less than 5.0 cm in diameter is much smaller than believed. Because their study is based on a geographically defined rather than referral population, Nevitt et al assert that their data closely approximate the true natural history of abdominal aortic aneurysms. PMID- 1860772 TI - Sternal mass in a patient with Paget's disease. PMID- 1860773 TI - Visual skill: correlation with detection of solitary pulmonary nodules. PMID- 1860774 TI - Guidelines for nursing management of people infected with human immunodeficiency virus (HIV)--W.H.O. PMID- 1860775 TI - Predicaments of the closed ward staff. AB - Coordinated team work is a sine qua non for efficient functioning of a therapeutic ward. Extreme violence on the part of a patient may disrupt the working relationship within the team to the extent of causing its members to question their choice of profession. Physical assaults and allegations of professional or personal misconduct brought forward by a patient and his/her family may undermine the competence of the attending staff. Recognition by the health, legal and psychiatric authorities of the difficulties to which the personnel on an acute closed ward is continually exposed may alleviate staff burnout. This in turn will contribute to better management of the patients. PMID- 1860776 TI - Measuring psychological stress in primary care military medical clinics. AB - In this study, the amount of psychological distress reported by soldiers is investigated and measured over time. The soldiers--enlisted and career--were randomly chosen while visiting five different military primary care clinics (for ostensible somatic problems) and administered the General Health Questionnaire (Goldberg and Huxley, 1980). A third of the subjects were given the GHQ a year later. Fifty-two percent showed psychological stress: combat soldiers showed considerably less distress than technical/maintenance and administrative soldiers, and the psychological stress findings remained relatively stable over time. Possible explanations for these findings are discussed. PMID- 1860777 TI - Head lice in drawings of kindergarten children. AB - Drawings by kindergarten children were analyzed in order to study the emotional reaction of these children to head lice. The choice of color was significant (black was used by 43% of the children, indicating that the subject of lice is associated with anxiety and fear) as were the unhappy faces and omissions of mouths in the drawings. While we know today that lice do not discriminate between clean and dirty hair, parents and professionals react very negatively to the condition, and this feeling is transferred to children as indicated by their drawings. PMID- 1860778 TI - Munchausen syndrome by adult proxy revisited. AB - A new variant of Munchausen Syndrome by Proxy (MSbP) case is presented here: Munchausen by Adult Proxy (MSbAP). The article discusses the case of a man (publicly known as the "Gasoline Injector") who is serving a 46-year jail term for attempted murder and manslaughter. His behavior is reminiscent of MSbP but his victims were two female adults, and his cell mate (on whom he repeated his actions). A description is given in terms of egosyntonic irresistible pathological impulses involving sexual objects. A common ground is proposed for paraphilias, Munchausen syndrome, MSbP and MSbAP. PMID- 1860779 TI - Drug induced suicidal ideation. AB - The authors present a case study of a mentally healthy man who repeatedly experienced short-lived, obsessional-like suicidal ideas and images after ingestion of the anti-fungal drug ketoconazole. Ego-alien, suicidal ideas are an extremely rare form of adverse drug reaction. This is probably the first report of drug-induced ego-dystonic, mood incongruent suicidal ideas appearing in a fully conscious, healthy individual. PMID- 1860780 TI - Perestroika and the Jewish problem. PMID- 1860781 TI - Two models of brief strategic therapy: the MRI model and the de Shazer model. AB - This paper presents and compares two models of brief strategic therapy: the MRI model, and the de Shazer model. Both models were implemented simultaneously in a community mental health child clinic. Each model is presented, and then illustrated by a case study. Apparent are the benefits that can be gained through exposure to each model, and the point that premature integration of the models might detract from the processes. The staff members' experience with the two models, and the differences in the therapist attitude are discussed. PMID- 1860782 TI - In vivo influences of phorbol ester and calcium ionophore on lymphocyte traffic, lymph flow and efferent lymph levels of thromboxane B2 in sheep. AB - In vitro systems have provided increasing evidence of significant lymphocyte transmembrane signalling by plasma membrane receptors which utilize antigen and other ligand activation of the inositol phosphate dual second messenger system of intracellular signalling. Elevation of intracellular Ca2+ and activation of protein kinase C are important products of these signals and appear to provide a complete set of mitogenic signals for both T and B cells. Calcium inophore and phorbol ester have been found to mimic these events in vitro and are here employed in vitro to study their effects on lymphocyte traffic and efferent lymph flow through primary peripheral lymph nodes of sheep and on the output into efferent lymph of the arachidonic acid metabolite, thromboxane B2. Calcium ionophore and phorbol ester were given alone or in combination to popliteal lymph nodes of sheep by drainage area injection or by acute infusion into cannulated afferent lympatics of study popliteal lymph nodes whose efferent lymphatic was chronically cannulated for study. The findings resembled those of drainage area immunization with an early increase in efferent lymph flow and prompt and marked depressions in the output into efferent lymph of both small recirculating and blast lymphocytes ('shutdown', 'recruitment'), followed by a marked increase in the output into efferent lymph of both small recirculating and blast lymphocytes. The greatest elevation in both small recirculating and blast lymphocyte outputs was at 24 and 48 h following phorbol ester and calcium ionophore administration. Acute phorbol ester and calcium ionophore administration was associated with a prompt and marked elevation in efferent lymph levels of thromboxane B2 which were of short duration. The findings observed here with lymph node drainage area infusion/injection of both phorbol ester and calcium ionophore are quite similar to those encountered in this sheep lymphocyte traffic model following popliteal lymph node drainage area immunization with killed Salmonella muenchen antigen. PMID- 1860783 TI - Effect of the double-stranded polynucleotide complex polyadenylate-polyuridylate (poly A-U) on interleukin-6 production by mouse fibroblasts. AB - Cultures of mouse embryonic fibroblasts (L 929) have been shown to produce a factor which promotes the growth of B cell hybridoma (hybridoma growth factor, HGF) i.e. interleukin 6 (IL-6). The aim of the present study was to investigate the effect of Poly A-U on IL-6 production by this cell type. After incubation for 48 h at 37 degrees C of confluent (1 week old) L 929 fibroblasts in the presence or in the absence of Poly A-U, IL-6-like activity in supernatants was measured by the proliferation assay of the IL-6-dependent B cell hybridoma cell line, 7TD1. Poly A-U increased IL-6 activity in supernatants in a dose-dependent manner at doses higher than 50 micrograms/ml, the maximum activity being observed at the highest concentration of Poly A-U used, i.e. 500 micrograms/ml. beta Interleukin 1 (beta IL-1) and poly-cytidylic-polyinosinic (Poly I-C) have been shown to be inducers of IL-6 in fibroblast culture and thus their effect was compared to that of Poly A-U. The IL-6 activity in supernatants induced by 500 micrograms/ml Poly I-C (58.4 +/- 16.4 U/ml; n = 4) was higher than that evoked by 100 U/ml beta IL-1 (5.7 +/- 0.4 U/ml) or 500 micrograms/ml Poly A-U (39.6 +/- 7.8 U/ml). The increased production of IL-6 by Poly A-U may explain part of its previously reported immunomodulatory effects. PMID- 1860784 TI - Inhibition of lymphocyte proliferation by amantadine and its isomer, 2 aminoadamantane; impact on Lyt-2+ T cells while sparing L3T4+ T cells. AB - The present in vitro investigations on amantadine (AmTd) and its isomer 2 aminoadamantane (2-NH2-Adam), and the corresponding analogs, 1-nitroadamantane (1 NO2-Adam) and 2-nitroadamantane (2-NO2-Adam), were undertaken to gain information about molecular features that might have a dominant role in inhibiting T lymphocyte proliferation and to determine whether all, or a subpopulation of thymic-dependent (T) lymphocytes might be impacted by these drugs. Studies were done using lymphocytes from untreated normal mice as well as cloned murine cytotoxic T lymphocytes, CTLL cells. T lymphocytes were defined by their proliferative response to concanavalin A (Con A), and thymic-independent (B) lymphocytes by their proliferative response lipopolysaccharide (LPS). Proliferation of CTLL cells was induced by supplementing the culture medium with lymphokine-containing medium or by adding recombinant interleukin (IL)-2. Proliferation was assessed by quantifying cellular incorporation of tritiated thymidine. The data show that the aminoadamantanes, AmTd and 2-NH2-Adam, impacted on Lyt-2+ T lymphocytes while sparing L3T4+ T lymphocytes. In addition, the data show that the location of the substituent group on the adamantane ring altered the molecule's capacity to modulate lymphocyte activity. And finally, results of studies comparing the inhibitory activity of AmTd and 1-NO2-Adam suggest a non lysosomal mechanism of action. Possible implications of these findings are discussed. PMID- 1860785 TI - Cellular and biochemical studies of substituted guanine ribonucleoside immunostimulants. PMID- 1860786 TI - Questionnaire versus clinical interview in the diagnosis of headache. AB - A self-administered questionnaire based on the operational diagnostic criteria of the International Headache Society (IHS) was evaluated in a cross-sectional epidemiological survey of headache disorders. A clinical interview was used as index of validity. Seven hundred and thirteen subjects were included. Sensitivity, specificity, predictive value, and chance-corrected agreement rate for the diagnosis of migraine was 51%, 92%, 50% (PVpos), 93% (PVneg), and 0.43 respectively. Corresponding values for episodic tension-type headache were 43%, 96%, 95% (PVpos), 46% (PVneg), and 0.30; and for chronic tension-type headache 14%, 100%, 100% (PVpos), 97% (PVneg), and 0.24. It is concluded that a questionnaire is not a satisfactory tool in diagnosing headache disorders according to the IHS criteria. The methods of data collection seem to have significant influence on the results. Caution in handling data obtained by means of subjective statements is advocated. PMID- 1860787 TI - Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. AB - The effects of oral Magnesium (Mg) pyrrolidone carboxylic acid were evaluated in 20 patients affected by menstrual migraine, in a double-blind, placebo controlled study. After a two cycles run-in period, the treatment (360 mg/day of Mg or placebo) started on the 15th day of the cycle and continued till the next menses, for two months. Oral Mg was then supplemented in an open design for the next two months. At the 2nd month, the Pain Total Index was decreased by both Placebo and Mg, with patients receiving active drug showing the lowest values (P less than 0.03). The number of days with headache was reduced only in the patients on active drug. Mg treatment also improved premenstrual complaints, as demonstrated by the significant reduction of Menstrual Distress Questionnaire (MDQ) scores. The reduction of PTI and MDQ scores was observed also at the 4th month of treatment, when Mg was supplemented in all the patients. Intracellular Mg++ levels in patients with menstrual migraine were reduced compared to controls. During oral Mg treatment, the Mg++ content of Lymphocytes (LC) and Polymorphonucleated cells (PMN) significantly increased, while no changes in plasma or Red Blood Cells were found. An inverse correlation between PTI and Mg++ content in PMN was demonstrated. These data point to magnesium supplementation as a further means for menstrual migraine prophylaxis, and support the possibility that a lower migraine threshold could be related to magnesium deficiency. PMID- 1860788 TI - Anger and hostility in tension-type headache. AB - A battery of standardized psychometric tests was administered to a group of 47 episodic tension-type headache sufferers and 47 headache-free controls. Compared to controls, headache subjects showed higher levels of anxiety, depression, and anger/hostility. The groups did not differ significantly on a measure of anger expressed toward persons or objects, but headache subjects showed significantly greater levels of suppressed anger. The results provide objective data that are in general agreement with predictions derived from psychosomatic theories about the interrelationships among anxiety, PMID- 1860789 TI - Decreased serum interleukin-2 level in patients with chronic headache. AB - Some cellular immune functions are impaired in cluster headache patients. Interleukin-2 (IL-2) is a polypeptide secreted by antigen or mitogen-actuated T lymphocytes that functions as a growth factor for T cells. To investigate cellular immune functions in patients with chronic headache, we measured the IL-2 concentration of sera in patients with migraine and in patients with tension-type headache. Thirteen subjects suffering from migraine without aura (5 males and 8 females, mean age: 32.8 years) and 46 subjects (20 males and 26 females, mean age: 39.7 years) with tension-type headache (TH) were selected for this study. Forty-three normal healthy volunteers composed the control group (15 males and 28 females, average age 41.6 years). The IL-2 levels of sera were determined using enzyme-linked immunosorbent assay (ELISA) techniques. The IL-2 levels of sera were 3.18 +/- 1.8 U/ml (mean +/- SD) in the healthy controls, 2.29 +/- 2.6 U/ml in the patients with migraine and 1.59 +/- 1.0 U/ml in the patients with TH. The serum level of IL-2 in the patients with migraine was significantly lower than in the controls. The serum level of IL-2 in the patients with TH was significantly lower than in the controls. The central nervous system (CNS) has been considered to be involved in the development of the immune phenomena. In the patients with TH or migraine, reduction in platelet 5-hydroxytryptamine (5-HT) levels and sympathetic hypofunction have been observed. These phenomena might reflect decrease in 5-HT levels in CNS in the patients with TH or migraine. The decreased serum IL-2 level, observed in this study, might reflect a reduction in 5-HT or catecholamine levels in CNS in the patients with migraine or TH. PMID- 1860790 TI - Activation of pain fibers to the internal carotid artery intracranially may cause the pain and local signs of reduced sympathetic and enhanced parasympathetic activity in cluster headache. AB - Several clinical and circulatory physiological observations indicate that the internal carotid artery (ICA) with proximal pial and orbital-periorbital branches, as well as external carotid vessels adjacent to the orbital region, are involved in the autonomic symptoms of an attack of cluster headache. Evidence is presented here that an activation of pain fibers innervating the intracranial segment of ICA may cause not only the retroorbital pain of an attack but also, via the mechanical effect of a neurogenic inflammation in the vessel wall, the local symptoms of a sympathetic defect and, via a reflex are to the parasympathetic pathway along the greater superficial petrosal nerve, the local symptoms from glands and vessels of parasympathetic discharge. Dilation of the intracranial ICA due to activation of this parasympathetic pathway may aggravate pain. Possible mechanisms behind such a local pain fiber activation are discussed. PMID- 1860791 TI - EMG activity in pericranial muscles during postural variation and mental activity in healthy volunteers and patients with chronic tension type headache. AB - EMG activity was recorded over frontalis, temporalis and trapezius muscles in a supine position, a standing position and during a mental task in 32 female patients suffering from chronic tension-type headache and in 20 healthy volunteers. Measurements in patients were made before and after biofeedback therapy. All EMG levels were on average significantly higher in patients than in controls. 62.5% of patients had at least one abnormal EMG level, but only 34% were beyond the normal range, if 1 muscle and 1 recording condition was considered. EMG levels were not correlated with headache severity, anxiety or response to biofeedback treatment. It is therefore suggested that pericranial EMG activity is not pathogenetic in chronic tension type headache, but merely one of several pathophysiologic changes, that are produced by a central dysfunction. PMID- 1860792 TI - Headache syndromes as detected by configural frequency analysis. AB - Data on headache symptoms obtained in two samples (N = 422 and 304) by means of questionnaires were subjected to configural frequency analysis (CFA). This not widely-known method tests whether certain symptom combinations appear more often or less often than expected by chance. In both samples symptom combinations corresponding to the syndromes of migraine with aura, migraine without aura and tension headache did indeed occur with significant frequency. The same clear-cut symptom patterns appeared when patients with preceding visual disturbances were excluded from analysis. These results seem to lend strong support to a categorical model of headache, rather than to the concept of headache as a spectrum. PMID- 1860793 TI - The impact of cigarette smoking on headache activity in headache patients. AB - The present study was designed to explore the relationship between cigarette smoking and headache activity in a sample of patients presenting for treatment. Subjects completed various self-report measures and monitored headache activity four times per day over a 4-week period. Analyses revealed that smokers experienced greater weekly peak headache intensity, and reported higher levels of depression and general physical symptoms. Among smokers, nicotine content of the preferred brand was associated with mean headache index and weekly headache-free days, as well as depression and anxiety scores. Daily smoking rate and pack-year history were related to level of general physical symptoms only. Thus, both smoking status and the nicotine content of the preferred cigarette appear to adversely impact headache activity. Further, smokers who are more anxious or depressed may increase their headache activity via their preference for higher nicotine-content cigarettes. These results are discussed in the context of possible mechanisms underlying these effects, and implications for the clinical management of headache suffers who smoke. PMID- 1860794 TI - Hemicrania continua: a therapeutic dilemma. PMID- 1860795 TI - Naproxen for perimenstrual headache. PMID- 1860796 TI - [Not diagnosable malignant melanomas]. AB - Of the 3574 malignant melanomas treated in Hornheide between December 1981 and August 1990 (not including preinvasive cases) 97 were not immediately recognized. These tumours did not look like melanomas. In 72% they were smaller than 10 mm in diameter, and in 20%, smaller than 5 mm. Clark's so often quoted "pencil rule" should no longer be used as an aid to exclusion of invasive melanoma. Localization of the unrecognized melanomas was on the head and neck in 22% of cases. In 37%, the patients were under the age of 40 years. No less than 25% of the patients had multiple melanomas. Many of these melanomas. Many of these melanomas were thin tumours (less than 0.75 mm in 55% and less than 1.5 mm in 77%). This explains why more than 50% of the lesions are described as "macules". The most common incorrect diagnoses were dysplastic naevi (44%) and common (23%) naevi. The most important anamnestic criteria are the patients' own statements about changes in size, colour and shape. These "dynamic" elements must be more carefully observed and documented during process of the clinical diagnosis. PMID- 1860798 TI - [Cryofibrinogenemia--successful therapy by decreasing fibrinogen]. AB - Six patients suffering from solitary cryofibrinogenaemia are described. In one patient idiopathic cryofibrinogenaemia was present, while the others showed secondary cryofibrinogenaemia associated with borrelia infection, chronic venous insufficiency with pulmonary embolism, primary biliary cirrhosis, diabetes mellitus or von-Willebrand syndrome. Subcutaneous injections of the thrombin-like snake poison batroxobin/ancrod were administered over a period of several weeks. Five patients experienced almost complete remission of their symptoms, especially of pain following cold exposure. In one patient partial relief was achieved. Overall we found a 75% reduction of symptoms. When blood fibrinogen levels are carefully monitored this therapy is an efficient and safe form of treatment for cryofibrinogenaemia. PMID- 1860797 TI - [Plaque-like dermal fibromatosis]. AB - Plaquelike dermal fibromatosis with a preference for the periaxillary region is described in 22 women, 1 man and 2 boys before puberty. The lesions grew slowly but relentlessly and measured up to 5 cm in diameter. No recurrences after excision have occurred to date. Histologically there is bandlike proliferation throughout the stratum reticulare consisting of well-differentiated, highly cellular fibrous tissue. PMID- 1860799 TI - [Electron microscopy findings in human spermatozoa with flagellar defects]. AB - Spermatozoal motility disorders must be interpreted with reference to whether the flagella are intact or impaired. A new classification of alterations of midpiece and flagellum includes a shaft disturbance that is increasingly often observed and can be recognized by light microscopy. Electron microscope examinations have shown that missing or poorly developed outer dense fibres are one cause of this flagellar disorder. As suitable longitudinal sections are rarely obtained in transmission electron microscopy, the negative staining technique was used in addition for this purpose. This method was found to be most suitable for an exact analysis of the periaxonemal structures of the sperm flagellum. Consideration of this hitherto unknown flagellar disturbance is important, because various therapeutic approaches have had little success so far and patients should be referred in good time for other gynaecological or andrological treatments. PMID- 1860800 TI - [A classical form of eosinophilic pustular folliculitis--successful therapy with PUVA]. AB - Eosinophilic pustular folliculitis was first defined by Ofuji et al. in 1970 [13]. It is reported most frequently in Japanese patients. It is characterized by the repetitive appearance of sterile papulopustular lesions that heal without scarring. Case reports from outside Japan frequently refer to ulcerating inflammation. We describe a classic form of eosinophilic pustular folliculitis in an European, and we show for the first time that the eosinophilic pustular folliculitis responds well to PUVA treatment. PMID- 1860801 TI - [Spinocellular cancers and myxoid atypical fibroxanthoma of an actinically damaged burn scar]. AB - We report on a 66-year-old male patient suffering from several squamous cell carcinomas and a myxoid atypical fibroxanthoma of the skin. The tumours developed in burn scars that the patient had had for more than 50 years and that had in part undergone actinic elastosis. The role of burn scars in the development of different skin tumours is pointed out. In addition, we discuss the differential diagnosis of the rare myxoid variant of atypical fibroxanthoma. PMID- 1860802 TI - [Multilocular, immature-cell myelogenous infiltrates of the skin in a patient with chronic myelomonocytic leukemia following polycythemia vera and anti cardiolipin syndrome]. AB - We report a 65-year-old patient presenting with disseminated, reddish, thick infiltrates and nodules during chronic myelomonocytic leukaemia and anticardiolipin syndrome. Histological and immunohistochemical investigations revealed immature myelogenous skin infiltrates. PMID- 1860803 TI - [4th Meeting of the Work Committee of Dermatologic Angiology of the German Dermatology Association]. PMID- 1860805 TI - [Meeting on "New Trends in Allergy III"]. PMID- 1860804 TI - [72d Annual Meeting of the Swiss Association of Dermatology and Venereology]. PMID- 1860806 TI - [Drastic increase in syphilis incidence in West Saxony]. PMID- 1860807 TI - [Education in dermatologic surgery. Wound closure]. PMID- 1860809 TI - Using CAHD. PMID- 1860808 TI - Computer-Aided Health Devices--the link to our next 20 years. PMID- 1860810 TI - Needlestick-prevention devices. PMID- 1860811 TI - Introducing HECS 3.0. PMID- 1860812 TI - Isolation and initial characterization of a series of Chlamydia trachomatis isolates selected for hydroxyurea resistance by a stepwise procedure. AB - Chlamydiae are obligate intracellular bacteria that are dependent on eukaryotic host cells for ribonucleoside triphosphates but not deoxyribonucleotide triphosphates. Ribonucleotide reductase is the only enzyme known to catalyze the direct conversion of a ribonucleotide to a deoxyribonucleotide. Hydroxyurea inhibits ribonucleotide reductase by inactivating the tyrosine free radical present in the small subunit of the enzyme. In this report, we show that Chlamydia trachomatis growth is inhibited by hydroxyurea in both wild-type mouse L cells and hydroxyurea-resistant mouse L cells. Hydroxyurea was used as a selective agent in culture to isolate, by a stepwise procedure, a series of C. trachomatis isolates with increasing levels of resistance to the cytotoxic effects of the drug. One of the drug-resistant C. trachomatis isolates (L2HR 10.0) was studied in more detail. L2HR-10.0 retained its drug resistance phenotype even after passage in the absence of hydroxyurea for 10 growth cycles. In addition, L2HR-10.0 was cross resistant to guanazole, another inhibitor of ribonucleotide reductase. Results obtained from hydroxyurea inhibition studies using various host cell-parasite combinations indicated that inhibition of host cell and C. trachomatis DNA synthesis by hydroxyurea can occur but need not occur simultaneously. Crude extract prepared from highly purified C. trachomatis reticulate bodies was capable of reducing CDP to dCDP. The CDP reductase activity was not inhibited by monoclonal antibodies to the large and small subunits of mammalian ribonucleotide reductase, suggesting that the activity is chlamydia specific. The CDP reductase activity was inhibited by hydroxyurea. Crude extract prepared from drug-resistant L2HR-10.0 reticulate bodies contained an elevation in ribonucleotide reductase activity. In total, our results indicate that C. trachomatis obtains the precursors for DNA synthesis as ribonucleotides with subsequent conversion to deoxyribonucleotides catalyzed by a chlamydia-specific ribonucleotide reductase. PMID- 1860813 TI - Genetic evidence for interaction between the CheW and Tsr proteins during chemoreceptor signaling by Escherichia coli. AB - This study presents two lines of genetic evidence consistent with the premise that CheW, a cytoplasmic component of the chemotactic signaling system of Escherichia coli, interacts directly with Tsr, the membrane-bound serine chemoreceptor. (i) We demonstrated phenotypic suppression between 10 missense mutant CheW proteins and six missense mutant Tsr proteins. Most of these mutant proteins had leaky chemotaxis defects and were partially dominant, implying relatively minor functional alterations. Their suppression pattern was allele specific, suggesting that the mutant proteins have compensatory conformational changes at sites of interactive contact. (ii) We isolated five partially dominant CheW mutations and found that four of them were similar or identical to the suppressible CheW mutant proteins. This implies that there are only a few ways in which CheW function can be altered to produce dominant defects and that dominance is mediated through interactions of CheW with Tsr. The amino acid replacements in these mutant proteins were inferred from their DNA sequence changes. The CheW mutations were located in five regularly spaced clusters in the first two-thirds of the protein. The Tsr mutations were located in a highly conserved region in the middle of the cytoplasmic signaling domain. The hydrophobic moments, overall hydrophobicities, and predicted secondary structures of the mutant segments were consistent with the possibility that they are located at the surface of the CheW and Tsr molecules and represent the contact sites between these two proteins. PMID- 1860814 TI - Methylamine metabolism in Hansenula polymorpha: an in vivo 13C and 31P nuclear magnetic resonance study. AB - Methylamine uptake, oxidation, and assimilation were studied in Hansenula polymorpha, a methylotrophic yeast. The constitutive ammonia transport system was shown to be effective at accumulating methylamine within cells cultured with methylamine or ammonia as a nitrogen source. [13C]methylamine oxidation rates were measured in vivo in methylamine-adapted cells by 13C nuclear magnetic resonance and were found to be lower than its uptake rate into the cells. The 13C label of methylamine was found exclusively in trehalose and glycerol, and [13C]formaldehyde was also extensively assimilated, indicating the presence of an assimilation pathway for the methylamine carbon. In vivo 31P nuclear magnetic resonance analysis showed major differences in the endogenous polyphosphate levels and mean chain length during adaptation of the cells from ammonia to methylamine, indicating that methylamine accumulated in the vacuole in the same manner as basic amino acids and purines. [13C]glucose metabolism was drastically altered during adaptation of the cells from ammonia to methylamine as a nitrogen source. The total rate of glucose utilization and the rate of ethanol production fell. Direct trehalose synthesis from glucose increased, indicating a switch from carbon utilization for growth to that for storage. The rate of methylamine oxidation was sufficient to support a much higher flow of carbon into central biosynthetic pathways. These results suggest that this reduction in biosynthetic carbon flow, rather than nitrogen availability, was the main factor responsible for reducing the growth rate of the yeast when ammonia was replaced by methylamine as the nitrogen source. PMID- 1860815 TI - Saturation mutagenesis of the UASNTR (GATAA) responsible for nitrogen catabolite repression-sensitive transcriptional activation of the allantoin pathway genes in Saccharomyces cerevisiae. AB - Saturation mutagenesis of the UASNTR element responsible for GLN3-dependent, nitrogen catabolite repression-sensitive transcriptional activation of allantoin pathway genes in yeast cells identified the dodecanucleotide sequence 5' TTNCTGATAAGG-3' as the minimum required for UAS activity. There was significant flexibility in mutant sequences capable of supporting UAS activity, which correlates well with the high variation in UASNTR homologous sequences reported to be upstream of the DAL and DUR genes. Three of nine UASNTR-like sequences 5' of the DAL5 gene supported high-level transcriptional activation. The others, which contained nonpermissive substitutions, were not active. PMID- 1860817 TI - Tryptophan gene cluster of Methanobacterium thermoautotrophicum Marburg: molecular cloning and nucleotide sequence of a putative trpEGCFBAD operon. AB - A recombinant cosmid carrying the Methanobacterium thermoautotrophicum Marburg trp genes was selected by complementation of Escherichia coli trp mutations. A 7.3-kb fragment of the cloned archaeal DNA was sequenced. It contained the seven trp genes, arranged adjacent to each other in the order trpEGCFBAD. No gene fusions were observed. The trp genes were organized in an operonlike structure, with four short (5- to 56-bp) intergenic regions and two overlapping genes. There was no indication for an open reading frame encoding a leader peptide in the upstream region of trpE. The gene order observed in the M. thermoautotrophicum trp operon was different from all known arrangements of the trp genes in archaea, bacteria, and eucarya. The encoded sequences of the Methanobacterium Trp proteins were similar in size to their bacterial and eucaryal counterparts, and all of them contained the segments of highly similar or invariant amino acid residues recognized in the Trp enzymes from bacteria and eucarya. The TrpE, TrpG, TrpC, TrpA, and TrpD proteins were 30 to 50% identical to those from representatives of other species. Significantly less sequence conservation (18 to 30%) was observed for TrpF, and TrpB exhibited a high degree of identity (50 to 62%) to the sequences of representatives of the three domains. With the exception of TrpB, the beta subunit of tryptophan synthase, tryptophan was absent from all Trp polypeptides. PMID- 1860816 TI - Analysis of virC, an operon involved in the secretion of Yop proteins by Yersinia enterocolitica. AB - Upon incubation at 37 degrees C in the absence of Ca2+ ions, pathogenic yersiniae release large amounts of pYV plasmid-encoded proteins called Yops that are involved in pathogenesis. Yersinia enterocolitica also expresses an outer membrane protein that is considered an adhesin and called YadA (previously called P1 or YopA). The production of Yops is coordinately regulated by a 20-kb region of the plasmid referred to as the Ca2+ dependence region and containing at least four loci called virA, virB, virC, and virF. The virF gene encodes a key transcriptional activator of yop genes. We have shown here that virF is also required for transcription of yadA and that virB is necessary for full transcription of the yop and yadA genes. In contrast, mutations in genes virA and virC had only a weak influence on the transcription of yop and yadA genes. These mutations did not affect the production of YadA but they completely inhibited the translocation of Yops from the intracellular compartment to the extracellular milieu. We inferred from these data that virA and virC are involved in the specific transport of Yops. We analyzed the 8.5-kb virC region and showed that it is most probably a single operon containing 13 open reading frames called yscA to yscM (for Yop secretion). Protein YscC has a putative signal sequence and shares significant homology with outer membrane proteins involved in the secretion of pullulanase by Klebsiella pneumoniae (PulD) or in the assembly of filamentous bacteriophages (gene IV product). At least the putative products of yscD, yscJ, and yscL were shown to be required for the export of Yops. YscJ turned out to be YlpB, a lipoprotein that we had detected previously. The yscM gene shares homology with yopH, the adjacent gene on the pYV plasmid. Its product does not appear to be necessary for the production of Yops. Transcription of the virC operon was subjected to the same regulation as the yop genes. PMID- 1860818 TI - Resuscitation of Vibrio vulnificus from the viable but nonculturable state. AB - Stationary-phase-grown cells of the estuarine bacterium Vibrio vulnificus became nonculturable in nutrient-limited artificial seawater microcosms after 27 days at 5 degrees C. When the nonculturable cells were subjected to temperature upshift by being placed at room temperature, the original bacterial numbers were detectable by plate counts after 3 days, with a corresponding increase in the direct viable counts from 3% to over 80% of the total cell count. No increase in the total cell count was observed during resuscitation, indicating that the plate count increases were not due to growth of a few culturable cells. Chloramphenicol and ampicillin totally inhibited resuscitation of the nonculturable cells when added to samples that had been at room temperature for up to 24 h. After 72 h of resuscitation, the inhibitors had an easily detectable but reduced effect on the resuscitated cells, indicating that protein and peptidoglycan synthesis were still ongoing. Major changes in the morphology of the cells were discovered. Nonculturable cells of V. vulnificus were small cocci (approximately 1.0 micron in diameter). Upon resuscitation, the cells became large rods with a size of mid log-phase cells (3.0 microns in length). Four days after the cells had become fully resuscitated, the cell size had decreased to approximately 1.5 micron in length and 0.7 micron in width. The cells were able to go through at least two cycles of nonculturability and subsequent resuscitation without changes in the total cell count. This is the first report of resuscitation, without the addition of nutrient, of nonculturable cells, and it is suggested that temperature may be the determining factor in the resuscitation from this survival, or adaptation, state of certain species in estuarine environments. PMID- 1860819 TI - Mutational analysis of repression and activation of the tyrP gene in Escherichia coli. AB - In a previous report it had been suggested that the tyrP gene of Escherichia coli may be expressed from two separate promoters. We have endeavored to confirm this suggestion by primer extension studies and the separate subcloning of each of these promoters. In these studies, we found a single promoter whose expression was repressed by TyrR protein in the presence of tyrosine and activated by TyrR protein in the presence of phenylalanine. Two adjacent TYR R boxes, with the downstream one overlapping the tyrP promoter, are the likely targets for the action of TyrR protein. Mutational analysis showed that both TYR R boxes were required for tyrosine-mediated repression but that only the upstream box was required for phenylalanine-mediated activation. In vitro DNase protection studies established that whereas in the absence of tyrosine TyrR protein protected the region of DNA represented by the upstream box, at low TyrR protein concentrations both tyrosine and ATP were required to protect the region of DNA involving the downstream box and overlapping the RNA polymerase binding site. PMID- 1860820 TI - Importance of the position of TYR R boxes for repression and activation of the tyrP and aroF genes in Escherichia coli. AB - Tyrosine-mediated repression of aroF and tyrP was studied by inserting DNA sequences between the two adjacent TYR R boxes which, in each case, overlap the respective RNA polymerase binding sites of these genes. In both cases, repression was greatest when homologous regions of these two TYR R boxes were on the same face of the DNA helix and the boxes were directly adjacent. An insertion of 3 bases was sufficient to abolish repression, which was reestablished as the boxes became separated by one full turn of the helix. These observations, coupled with the results of in vitro DNase I protection studies, supported the hypothesis that the binding of TyrR protein to the downstream boxes required cooperative interaction with TyrR protein already bound to the upstream boxes. In the case of tyrP, moving the upstream box also affected activation. Maximal activation was observed when the box was moved 3 or 12 to 14 residues upstream. Practically no activation was seen at intermediate positions, such as +7 and -4. It is hypothesized that these results indicate positions allowing maximal interaction between TyrR protein bound to the upstream box and RNA polymerase bound to the RNA polymerase binding site. PMID- 1860821 TI - Analysis of Streptococcus pneumoniae sequences cloned into Escherichia coli: effect of promoter strength and transcription terminators. AB - Difficulties encountered in the cloning of DNA from Streptococcus pneumoniae and other AT-rich organisms into ColE1-type Escherichia coli vectors have been proposed to be due to the presence of a large number of strong promoter-acting sequences in the donor DNA. The use of transcription terminators has been advocated as a means of reducing instability resulting from disruption of plasmid replication caused by strong promoters. However, neither the existence of promoter-acting sequences of sufficient strength and number to explain the reported cloning difficulties nor their role as a source of instability has been proven. As a direct test of the "strong promoter" hypothesis, we cloned random fragments from S. pneumoniae into an E. coli vector containing transcription terminators, identified strong promoter-acting sequences, and subsequently removed the transcription terminators. We observed that terminator removal resulted in reduced copy numbers for the strongest promoter-acting sequences but not in reduced promoter strengths or altered plasmid stabilities. Our results indicate that promoters strong enough to require transcription terminators for plasmid stability are probably rare in S. pneumoniae DNA. PMID- 1860822 TI - Genetic and molecular analyses of picA, a plant-inducible locus on the Agrobacterium tumefaciens chromosome. AB - picA is an Agrobacterium tumefaciens chromosomal locus, identified by Mu d11681 mutagenesis, that is inducible by certain acidic polysaccharides found in carrot root extract. Cloning and genetic analysis of a picA::lacZ fusion defined a region of the picA promoter that is responsible for the induction of this locus. Furthermore, we identified a possible negative regulator of picA expression upstream of the picA locus. This sequence, denoted pgl, has extensive homology to polygalacturonase genes from several organisms and inhibited the induction of the picA promoter when present in multiple copies in A. tumefaciens. DNA sequence analysis indicated at least two long open reading frames (ORFs) in the picA region. S1 nuclease mapping was used to identify the transcription initiation site of picA. Mutation of ORF1, but not ORF2, of the picA locus was responsible for an increased aggregation of A. tumefaciens, forming "ropes" in the presence of pea root cap cells. In addition, a potato tuber disk virulence assay indicated that a preinduced picA mutant was more virulent than was the wild-type control, a further indication that the picA locus regulates the surface properties of the bacterium in the presence of plant cells or plant cell extracts. PMID- 1860823 TI - The Actinobacillus pleuropneumoniae hemolysin determinant: unlinked appCA and appBD loci flanked by pseudogenes. AB - The appBD genes encoding the secretion functions for the 110-kDa RTX hemolysin of Actinobacillus pleuropneumoniae have been cloned and sequenced. Unlike analogous genes from other RTX determinants, the appBD genes do not lie immediately downstream from the hemolysin structural gene, appA. Although isolated from a diverse group of gram-negative organisms, the appBD genes and the characterized RTX BD genes from other organisms all exhibit a high degree of homology at both the DNA and predicted amino acid sequence levels. Analysis of the DNA sequences 3' to appA and 5' to appB suggests that these regions harbor remnant RTX B and A pseudogenes, respectively. Although the appA gene is most similar to the lktA gene from Pasteurella haemolytica (Y. F. Chang, R. Young, and D. K. Struck, DNA 8:635-647, 1989), the RTX A pseudogene upstream from appB most closely resembles the hlyB gene from Escherichia coli, suggesting that the appCA and appBD operons were derived from different ancestral RTX determinants. PMID- 1860824 TI - Cloning, characterization, and expression in Escherichia coli of a gene encoding Listeria seeligeri catalase, a bacterial enzyme highly homologous to mammalian catalases. AB - A gene coding for catalase (hydrogen-peroxide:hydrogen-peroxide oxidoreductase; EC 1.11.1.6) of the gram-positive bacterium Listeria seeligeri was cloned from a plasmid library of EcoRI-digested chromosomal DNA, with Escherichia coli DH5 alpha as a host. The recombinant catalase was expressed in E. coli to an enzymatic activity approximately 50 times that of the combined E. coli catalases. The nucleotide sequence was determined, and the deduced amino acid sequence revealed 43.2% amino acid sequence identity between bovine liver catalase and L. seeligeri catalase. Most of the amino acid residues which are involved in catalytic activity, the formation of the active center accession channel, and heme binding in bovine liver catalase were also present in L. seeligeri catalase at the corresponding positions. The recombinant protein contained 488 amino acid residues and had a calculated molecular weight of 55,869. The predicted isoelectric point was 5.0. Enzymatic and genetic analyses showed that there is most probably a single catalase of this type in L. seeligeri. A perfect 21-bp inverted repeat, which was highly homologous to previously reported binding sequences of the Fur (ferric uptake regulon) protein of E. coli, was detected next to the putative promoter region of the L. seeligeri catalase gene. PMID- 1860825 TI - Identification and initial characterization of the eutF locus of Salmonella typhimurium. AB - We report the isolation and initial characterization of mutations in the newly described eutF locus of Salmonella typhimurium LT2. Mutations in eutF render a strain unable to utilize ethanolamine as a source of carbon and/or energy and impair growth on ethanolamine as a sole nitrogen source. Strains carrying eutF mutations exhibit a 2-order-of-magnitude decrease in transcription of the unlinked eutDEABCR operon (50 min), which codes for the enzymes needed to catabolize ethanolamine; have only 10% of the ethanolamine ammonia-lyase activity found in the wild type; and show a marked reduction in the rate of ethanolamine uptake. Deletion mapping and three-factor cross analysis results are consistent with the gene order cobA trp eutF tonB at 34 min on the linkage map. We discuss two possible roles for the EutF protein: (i) as an ethanolamine permease or (ii) as a transcription factor required for the expression of the eutDEABCR operon. PMID- 1860826 TI - Electrophoretic separation of the three Rhizobium meliloti replicons. AB - The megaplasmids and the chromosome from the bacterium Rhizobium meliloti 1021 were separated in preparative quantities by using transverse alternating-field gel electrophoresis. The genetic content of each electrophoretically separated band was determined by Southern hybridization with replicon-specific probes and by comparison with Agrobacterium tumefaciens transconjugants harboring either pSym-a or pSym-b megaplasmids. Pulsed-field gel electrophoresis analyses of PacI (5'-TTAATTAA-3') and SwaI (5'-ATTTAAAT-3') digests of the whole genome and of the separated replicons were used to calculate genome sizes in two R. meliloti strains. In these strains, PacI digestion yielded only four fragments for the entire genome. The sizes of the PacI fragments from R. meliloti 1021 in megabase pairs (Mb) were 3.32 +/- 0.30, 1.42 +/- 0.13, 1.21 +/- 0.10, and 0.55 +/- 0.08, for a total genome size of 6.50 +/- 0.61 Mb. Southern hybridization with replicon specific probes assigned one PacI fragment to the chromosome of R. meliloti 1021, one to pRme1021a, and two to pRme1021b. PacI digestion of A. tumefaciens pTi cured, pSym transconjugants confirmed these assignments. In agreement with PacI data, the addition of the six SwaI fragments from R. meliloti 1021 gave a genome size of 6.54 +/- 0.43 Mb. pRme1021a was calculated to be 1.42 +/- 0.13 Mb, 1.34 +/- 0.09 Mb, and 1.38 +/- 0.12 Mb on the basis of PacI digestion, SwaI digestion, and the migration of uncut pRme1021a, respectively. pRme1021b was calculated to be 1.76 +/- 0.18 Mb, 1.65 +/- 0.10 Mb, and 1.74 +/- 0.13 Mb on the basis of PacI digestion, SwaI digestion, and the migration of uncut pRme1021B, respectively. The R. meliloti 1021 chromosome was calculated to be 3.32 +/- 0.30 Mb, 3.55 +/- 0.24 Mb, and 3.26 +/- 0.46 Mb on the basis of PacI data, SwaI data, and the migration of uncut chromosome, respectively. PMID- 1860827 TI - Identification of the promoter region of the ribosome-releasing factor cistron (frr). AB - Previous studies of the structure and expression of the ribosome-releasing factor (RRF) cistron (frr) have suggested that an efficient promoter region is located in the RRF cistron. We report here on the nucleotide sequence and in vivo function of the RRF promoter. The transcriptional start site was determined by primer extension to be 58 bp upstream of the translational initiation codon of frr. The location of the RRF promoter region was confirmed by means of (i) deletion analysis of the 5' proximal sequences of frr fused to the chloramphenicol acetyltransferase reporter gene, (ii) analysis of RRF produced in vivo from the deletion derivatives of frr cloned into pUC19, and (iii) gel retardation analysis with Escherichia coli RNA polymerase. The -35 and -10 regions were TTacCc and TATAcT, respectively. The strength of the RRF promoter was similar to that of the lac promoter, as determined by in vivo expression of chloramphenicol acetyltransferase activity. However, the RRF promoter was not affected by the intracellular cyclic AMP level despite the presence of a cyclic AMP receptor protein binding site downstream of the RRF promoter. PMID- 1860828 TI - Suppression of the abnormal phenotype of Salmonella typhimurium rfaH mutants by mutations in the gene for transcription termination factor Rho. AB - Mutations in the rfaH gene have previously been shown to cause premature termination of transcription of the traYZ operon of the F factor and also to prevent expression of the rfaGBIJ gene cluster of Salmonella typhimurium. In the present study, mutants were selected for their ability to restore the normal pattern of rfaGBIJ function. On the basis of this initial section, several classes of extragenic suppressor mutants were isolated that completely or partially corrected the Tra- and Rfa- phenotypes of the prototype rfaH mutant. The suppressor mutations included mutations in rho and mutations that mapped in or close to rpoBC. Other suppressor mutations were located elsewhere on the chromosome, presumably identifying other genes that play a role in the RfaH mediated transcriptional regulation. PMID- 1860829 TI - Initiator (DnaA) protein concentration as a function of growth rate in Escherichia coli and Salmonella typhimurium. AB - The DnaA protein concentration was determined in five different Escherichia coli strains and in Salmonella typhimurium LT2 growing at different growth rates. The DnaA protein concentration was found to be invariant over a wide range of growth rates in the four E. coli K-12 strains and in S. typhimurium. In E. coli B/r the DnaA protein concentration was generally higher than in the K-12 strains, and it increased with decreasing growth rates. For all the strains, there appears to be a correlation between the DnaA protein concentration and the initiation mass. This supports the concept of the concentration of DnaA protein setting the initiation mass and, thus, that the DnaA protein is a key molecule in the regulation of initiation of chromosome replication in members of the family Enterobacteriaceae. PMID- 1860830 TI - A missense mutation in the rpoC gene affects chromosomal replication control in Escherichia coli. AB - An RNA polymerase mutant with a single-base-pair change in the rpoC gene affects chromosome initiation control. The mutation, which is recessive, is a G to A transition leading to the substitution of aspartate for glycine at amino acid residue 1033 in the RNA polymerase beta' subunit. The chromosome copy number is increased twofold in the mutant at semipermissive growth temperatures (39 degrees C). In a delta oriC strain, in which chromosome initiation is governed by an F replicon, chromosome copy number is not affected. Plasmid pBR322 copy number is also increased in the mutant at 39 degrees C. The mutation causes a more than fivefold increased expression of the dnaA gene at 39 degrees C. It is conceivable that it is this high DnaA concentration which causes the high chromosome copy number and that the mutant RNA polymerase beta' subunit exerts its effect by altering the expression of the dnaA gene. However, other factors must be affected as well to explain why the RNA polymerase mutant can grow in a balanced fashion with a high chromosome concentration. This is in contrast to wild-type cells, which exhibit higher origin concentrations when DnaA protein is overproduced, but in which the overall DNA concentration is only moderately affected. PMID- 1860831 TI - Transcriptional analysis of the Staphylococcus aureus plasmid pI258 mercury resistance determinant. AB - Northern blot DNA-RNA hybridization analysis of Staphylococcus aureus cells bearing pI258 showed that upon induction the amount of mer operon transcript present increased 49-fold over that observed in uninduced cells. Maximum induction occurred after 45 min in the presence of 5 microM HgCl2. Two transcripts, 5.0 and 5.8 kb long, were observed. Both transcripts encoded merR through merB (inclusive). Primer extension analysis determined that the 5' end of at least one transcript (and presumably of both) started at a T or G, 7 or 8 nucleotides downstream from the putative -10 site. PMID- 1860832 TI - Comparison of protein synthesis inhibition kinetics and cell killing induced by immunotoxins. AB - Immunotoxins comprised of a monoclonal antibody covalently coupled to recombinant ricin A chain or to a binding-defective form of diphtheria toxin were compared with respect to their rates of protein synthesis inhibition and efficiencies of killing target cells. Protein synthesis inhibition rates were established by measuring the incorporation of L-[14C]leucine in toxin-treated cells relative to untreated cells at several times after exposure of cells to an immunotoxin. Cell killing was assessed by a limiting dilution assay which measures the number of cells surviving toxin treatment relative to untreated cells. At equivalent protein concentrations, the diphtheria toxin immunotoxin inhibited protein synthesis significantly more rapidly than the ricin A immunotoxin but, contrary to previous predictions, achieved a significantly lower cell kill. Thus, the kinetics of protein synthesis inactivation do not necessarily correlate with killing efficiencies. Possible explanations for these results are that the effect of the diphtheria toxin immunotoxin on protein synthesis is partially reversible or that the diphtheria toxin immunotoxin enters the cytosol at a faster rate than the ricin A immunotoxin but also is degraded at a faster rate. PMID- 1860833 TI - Protein discharge from immature secretory granules displays both regulated and constitutive characteristics. AB - At physiological glucose concentrations, isolated pancreatic islets release a minor portion of their newly synthesized insulin and precursors in a phase of secretion which is largely complete by 4 h of chase. Discharge during this period can be amplified by secretagogues, yet is not abolished by conditions which fully suppress regulated release from dense core secretory granules. The ability to stimulate the secretion and the biochemical profile of released proinsulin related peptides indicate that secretion during this period originates from immature granules. The stoichiometry of release of labeled C-peptide:insulin during this phase is 1:1 at high glucose concentrations. However, at physiologic or low concentrations, C-peptide is released in molar excess of insulin as if the exocytotic vesicles carrying this secretion were budding from a post-Golgi compartment in which the lumen was composed of condensing insulin and soluble C peptide. These findings can be explained by a model for regulated secretory protein traffic in which direct exocytosis of young granules is stimulated by higher glucose concentrations and vesicle budding from immature granules occurs at lower concentrations. Thus, insulin targeting from immature granules exhibits both regulated and constitutive-like characteristics. PMID- 1860834 TI - Expression of a human cartilage procollagen gene (COL2A1) in mouse 3T3 cells. AB - Expression in a recombinant system has been difficult to obtain for any of the major fibrillar collagens that require processing by eight or more post translational enzymes. Here, two DNA constructs were designed so that the promoter region of the gene for the pro-alpha 1(I) chain of human type I procollagen drove expression of the human type II procollagen gene in mouse NIH 3T3 cells, a culture line that normally synthesizes type I procollagen but not any cartilage-specific protein such as type II procollagen. Both constructs were expressed as both mRNA and protein. In clones expressing the construct at high levels, the steady-state levels of mRNA and the production of type II procollagen were comparable to the mRNA levels and production of type I procollagen from the endogenous mouse genes. Comparison of clones containing the two constructs demonstrated that sequences extending 80 base pairs beyond the major polyadenylation signal of the gene are not in themselves sufficient for correct termination and 3' processing of RNA transcripts. The results strongly suggest that specific sequences present in a downstream 3.5-kilobase SphI/SphI fragment determine the termination of the transcription. Of special importance is that the system will make it possible to examine the consequences of mutations in the human type II procollagen gene on the processing of RNA transcripts and on the functional properties of the protein simply by using the genomic DNA from leukocytes or other non-cartilaginous sources. PMID- 1860835 TI - A retinoic acid-responsive human zinc finger gene, MZF-1, preferentially expressed in myeloid cells. AB - Zinc finger genes encode metal-binding proteins that can act as transcriptional regulators of other genes. In an effort to identify activators of the genetic cascade in hemopoietic differentiation, we used degenerate synthetic oligonucleotides to the conserved zinc finger histidine-cysteine link to probe a human myeloid lambda gt11 cDNA library. One of the cDNA clones obtained hybridized preferentially to mRNA from myeloid cells. This cDNA was used to isolate clones encompassing the coding region for this gene. Sequence analysis found 13 zinc finger regions and a glycine-proline-rich region between the fourth and fifth zinc finger domain. The gene was localized to chromosome 19q13.2-4, a chromosome that has a large cluster of zinc finger genes. The gene was preferentially expressed in myeloid leukemia cell lines with the highest mRNA levels noted in HL-60 cells induced to differentiate with retinoic acid. Thus, this new zinc finger gene (designated MZF-1) may be one regulator of transcriptional events during hemopoietic development. PMID- 1860836 TI - Interaction of the regulatory subunit (RII) of cAMP-dependent protein kinase with RII-anchoring proteins occurs through an amphipathic helix binding motif. AB - The type II cAMP-dependent protein kinase is localized to specific subcellular environments through the binding of the regulatory subunit (RII) dimer to RII anchoring proteins. Computer-aided analysis of secondary structure, performed on four RII-anchoring protein sequences (the microtubule-associated protein 2, P150, and two thyroid proteins Ht 21 and Ht 31), has identified common regions of approximately 14 residues which display high probabilities of forming amphipathic helices. The potential amphipathic helix region of Ht 31 (Leu-Ile-Glu-Glu-Ala-Ala Ser-Arg-Ile-Val-Asp-Ala-Val-Ile) lies between residues 494 and 507. A bacterially expressed 318-amino acid fragment, Ht 31 (418-736), containing the amphipathic helix region, was able to bind RII alpha. Site-directed mutagenesis designed to disrupt the secondary structure in the putative binding helix reduced binding dramatically. Specifically, substitution of proline for Ala-498 significantly diminished RII alpha binding, and similar mutation of Ile-502 or Ile-507 abolished interaction. Mutation of Ala-522 to proline, which is located outside the predicted amphipathic helix region, had no effect on RII alpha binding. These data suggest that anchoring proteins interact with RII alpha via an amphipathic helix binding motif. PMID- 1860837 TI - Characterization of a K26Q site-directed mutant of human parathyroid hormone expressed in yeast. AB - Human parathyroid hormone (hPTH) is susceptible to proteolytical cleavage both in humans and when expressed as a secretory product in Escherichia coli (Hogseth, A., Blingsmo, O. R., Saether, O., Gautvik, V. T., Holmgren, E., Hartmanis, M., Josephson, S., Gabrielsen, O. S., Gordeladze, J. O., Alestrom, P., and Gautvik, K. M. (1990) J. Biol. Chem. 265, 7338-7344) and Saccharomyces cerevisiae (Gabrielsen, O. S., Reppe, S., Saether, O., Blingsmo, O. R., Sletten, K., Gordeladze, J. O., Hogset, A., Gautvik, V. T., Alestrom, P., Oyen, T. B., and Gautvik, K. M. (1990) Gene (Amst.) 90, 255-262). In the latter system, one major site of cleavage was identified (Arg25-Lys26 decreased Lys27). To produce hPTH resistant to this proteolytic processing, a point mutation changing Lys26 to Gln was introduced, and the modified gene expressed in S. cerevisiae as a fusion protein with the alpha-factor leader sequence. The resulting major form of hPTH secreted to the growth medium was of full length showing that the mutation had eliminated internal processing. Consequently, the yield of the mutant hormone was significantly higher than obtained with the natural peptide. Using improved purification procedures, a significantly higher purity was also obtained. The secreted mutant hPTH-(1-84,Q26) had the correct size, full immunological reactivity with two different hPTH antisera, correct amino acid composition and N terminal sequence, and correct mass as determined by mass spectrometry. Furthermore, the introduced mutation did not reduce the biological activity of the hormone as judged from its action in three biological assay systems: 1) a hormone-sensitive osteoblast adenylate cyclase assay; 2) an in vivo calcium mobilizing assay in rats; and 3) an in vitro bone resorption assay. PMID- 1860838 TI - Mechanisms of bombesin-induced arachidonate mobilization in Swiss 3T3 fibroblasts. AB - A peptide mitogen bombesin, which activates the phospholipase C-protein kinase C signaling pathway, induces a mepacrine-sensitive, dose-dependent increase in the release of [3H]arachidonic acid and its metabolites ([3H]AA) from prelabeled Swiss 3T3 fibroblasts. The effect is temporally composed of two phases, i.e. an initial transient burst that is essentially independent of extracellular Ca2+, and a following sustained phase that is absolutely dependent on the extracellular Ca2+. The initial transient [3H]AA liberation occurs concomitantly with bombesin induced 45Ca efflux from prelabeled cells: both responses being substantially attenuated by loading cells with a Ca2+ chelator quin2. However, bombesin-induced intracellular Ca2+ mobilization by itself is not sufficient as a signal for the initial transient [3H]AA liberation, since A23187 potently stimulates 45Ca efflux to an extent comparable to bombesin but fails to induce [3H]AA release in the absence of extracellular Ca2+. The second sustained phase of the bombesin-induced [3H]AA release is abolished by reducing extracellular Ca2+ to 0.03 mM, although bombesin effects on phospholipase C and protein kinase C activation are barely affected by the same procedure. A protein kinase C activator phorbol 12,13 dibutyrate induces an extracellular Ca(2+)-dependent, slowly developing sustained increase in [3H]AA release, and markedly potentiates both phases of bombesin induced [3H]AA release. Down-regulation of cellular protein kinase C completely abolishes all of the effects of phorbol dibutyrate, and partially inhibits the second but not the first phase of bombesin-induced [3H]AA release. These results indicate that bombesin-induced receptor-mediated activation of phospholipase A2 involves multiple mechanisms, including intracellular Ca2+ mobilization for the first phase, protein kinase C activation plus Ca2+ influx for the second phase, and as yet unknown mechanism(s) independent of intracellular Ca2+ mobilization or protein kinase C for both of the phases. PMID- 1860839 TI - Residues in the alpha subunit of human choriotropin that are important for interaction with the lutropin receptor. AB - Synthetic peptides were used to probe the structure-function relationships between human choriotropin (hCG) and the lutropin (LH) receptor. Previously, a peptide region of the alpha subunit of hCG, residues 26-46, had been shown to inhibit binding of 125I-hCG to the LH receptor in rat ovarian membranes (Charlesworth, M.C., McCormick, D.J., Madden, B., and Ryan, R.J. (1987) J. Biol. Chem. 262, 13409-13416). To determine which residues are important for this inhibitory activity, peptides were truncated from either the amino or carboxyl terminus, or individual residues were substituted with alanine. The amino terminal boundary was determined to be Gly-30 and the carboxyl-terminal boundary, Lys-44. This core peptide contained all the residues needed for full activity of the parent peptide 26-46. Arg-35 and Phe-33 were particularly important residues; when they were substituted with alanine, the peptide inhibitory potencies were decreased. Ser-43, Arg-42, Cys-32, and Cys-31 were also important but to a lesser degree. These results are consistent with predictions based on chemical and enzymatic modification studies and provide insight into which residues are important for interaction between hCG and the LH receptor. PMID- 1860840 TI - Stopped-flow and rapid-scan studies of the redox behavior of cytochrome aco from facultative alkalophilic Bacillus. AB - Cytochrome aco purified from an alkalophilic bacterium grown at pH 10 contains hemes a, b, and c as prosthetic groups, and their redox behavior was examined by using stopped-flow and rapid-scan techniques. Under anaerobic conditions the reduction of both heme a and c moieties with dithionite proceeded exponentially but with different rates, usually the former being reduced about 4 times faster than the latter. The reduction of protoheme was much slower, and a time difference spectrum for this species was of a high spin type with absorption peaks at 433, 557, and 609 nm. Only the protoheme combined with CO, fulfilling the criteria for cytochrome o. Potentiometric titrations determined a midpoint potential of c heme to be 95 mV at pH 7.0 and 25 degrees C and suggested the presence of two forms of a heme with midpoint potentials of 250 and 323 mV. Cytochrome aco utilizes ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) to reduce oxygen relatively rapidly without added cytochrome c (Qureshi, M. H., Yumoto, I., Fujiwara, T., Fukumori, Y., Yamanaka, T. (1990) J. Biochem. 107, 480-485). During the steady state, however, heme a stayed almost fully reduced in contrast to a partial reduction of heme c. Even after exhaustion of the dissolved oxygen the extent of reduction of heme c was 60-70% that attained by the dithionite reduction. When ascorbate plus TMPD-reduced cytochrome aco was exposed to oxygen the reduced heme c was oxidized rapidly whereas the oxidation of reduced a heme was negligibly slow. The full reduction of heme a during the steady state and its extremely slow oxidation rendered participation of heme a in the oxidase reaction less likely. A novel peak appearing transiently around 567 nm during the reaction was tentatively ascribed to an intermediate form of protoheme, or o heme, which was thus supposed to react directly with molecular oxygen. These results suggest strongly that the main electron transfer pathway would be c----o----oxygen. A possible role of a in regulating the electron flow through the main pathway and its functional relationship to a heme in the aa3 type cytochrome oxidase were discussed. PMID- 1860841 TI - Characterization of active and latent forms of the membrane-associated sn glycerol-3-phosphate acyltransferase of Escherichia coli. AB - The intrinsically active, sn-glycerol-3-phosphate acyltransferase present in membranes prepared from both wild type Escherichia coli and from strains which overproduce the enzyme can be kinetically distinguished from a latent enzyme species which is unmasked by solubilization and reconstitution. Both membrane associated and solubilized/reconstituted enzyme preparations exhibited cooperativity with respect to sn-glycerol-3-phosphate and palmitoyl-coenzyme A substrates; positive cooperativity in membranes toward palmitoyl-coenzyme A (napp = 4) and negative cooperativity toward sn-glycerol-3-phosphate (napp = 0.75) were significantly altered upon solubilization and reconstitution. Since the degree of alteration increased with the amount of sn-glycerol-3-P acyltransferase present in the membranes, a detergent-dissociable homooligomerization of the sn-glycerol 3-phosphate acyltransferase was considered as an underlying mechanism. This possibility was investigated by changing the protein-to-Triton X-100 ratio of homogeneous enzyme prior to reconstitution and then analyzing the subsequent migration of samples on a Sephacryl S-300 sizing column. The elution positions were consistent with monomeric and dimeric polypeptide bound to micelles of Triton X-100. Hill coefficients for monomeric, reconstituted enzyme preparations were comparable to those obtained for the active, membrane-associated sn-glycerol 3-phosphate acyltransferase. The reduced cooperativity of dimeric, reconstituted enzyme preparations correlated closely to the Hill coefficient values obtained for latent, solubilized/reconstituted sn-glycerol-3-phosphate acyltransferase from membranes of Escherichia coli which overproduce the enzyme. The physiological significance of these findings is discussed. PMID- 1860842 TI - The P1 plasmid partition complex at parS. The influence of Escherichia coli integration host factor and of substrate topology. AB - The P1 ParB protein is required for active partition and thus stable inheritance of the plasmid prophage. ParB and the Escherichia coli protein integration host factor (IHF) participate in the assembly of a partition complex at the centromere like site parS. In this report the role of IHF in the formation of the partition complex has been explored. First, ParB protein was purified for these studies, which revealed that ParB forms a dimer in solution. Next, the IHF binding site was mapped to a 29-base pair region within parS, including the sequence TAACTGACTGTTT (which differs from the IHF consensus in two positions). IHF induced a strong bend in the DNA at its binding site. Versions of parS which have lost or damaged the IHF binding site bound ParB with greatly reduced affinity in vitro and in vivo. Measurements of binding constants showed that IHF increased ParB affinity for the wild-type parS site by about 10,000-fold. Finally, DNA supercoiling improved ParB binding in the presence of IHF but not in its absence. These observations led to the proposal that IHF and superhelicity assist ParB by promoting its precise positioning at parS, a spatial arrangement that results in a high affinity of ParB for parS. PMID- 1860843 TI - Receptor-mediated gene delivery in vivo. Partial correction of genetic analbuminemia in Nagase rats. AB - A plasmid (palb3) was constructed containing the structural gene for human serum albumin driven by mouse albumin enhancer-rat albumin promoter elements. Using an asialoglycoprotein-polycation conjugate consisting of asialoorosomucoid coupled to poly-L-lysine, a soluble DNA complex was formed that was capable of targeting specifically to hepatocytes via asialoglycoprotein receptors present on these cells. Groups of Nagase analbuminemic rats were injected with complexed DNA or controls, followed by two-thirds partial hepatectomy to stimulate hepatocyte replication. Using a cDNA probe for the human albumin structural gene, hybridizable sequences were detected in analbuminemic rats treated with complex as determined by Southern blot analysis. Two weeks post-injection, the targeted DNA was found to exist primarily in plasmid form with an average copy number of 1000/diploid cell. Human albumin mRNA was detected by dot-blot hybridization with a specific oligonucleotide cDNA probe and confirmed by RNase protection assay using a vector-specific probe. Circulating human albumin was detected in the serum of palb3-treated Nagase analbuminemic rats by Western blots using an antibody specific for human serum albumin. A time course demonstrated that circulating human albumin was not detectable 24 h after injection, but became measurable at a level of 0.05 micrograms/ml within 48 h and increased in concentration to a maximum of 34 micrograms/ml by 2 weeks post-injection. This level of expression remained stable through 4 weeks after injection and partial hepatectomy. PMID- 1860844 TI - Membrane fusion induced by mutual interaction of the two charge-reversed amphiphilic peptides at neutral pH. AB - An anionic amphiphilic peptide and the charge-reversed cationic peptide are synthesized. They contain 20 amino acids with the same sequence except for 5 Glu residues for the anionic versus 5 Lys residues for the cationic peptides. Fusion of egg phosphatidylcholine large unilamellar vesicles is assayed with the fluorescent probes by the lipid mixing and the internal content mixing at neutral pH. The peptide mixture causes a rapid and efficient membrane fusion, in spite of no fusions with each peptide by itself. Each peptide takes nearly random coils with a small amount of helix, but the peptide mixture has an ordered helical structure. The equimolar peptide mixture forms a much more hydrophobic complex than those of different molar ratios of peptides and also that of each peptide itself. The equimolar peptide mixture causes the most efficient fusion. Preincubations of two peptides before addition to vesicles cause the slower rates of fusion. The fusion is greatly reduced at higher ionic strength and nearly zero at 800 mM NaCl and 40 mM sodium phosphate. Each peptide and the peptide mixture show the same alpha-helical structure, interact with vesicles, but do not induce fusion at higher ionic strengths. These results suggest that the two peptides interact mutually through the electrostatic Coulombic interaction between the charged groups. The electrically neutralized hydrophobic complex aggregates the separate vesicles together and interacts with the hydrocarbon region of lipid bilayers to cause fusion. PMID- 1860845 TI - Human biglycan gene. Putative promoter, intron-exon junctions, and chromosomal localization. AB - Biglycan (PG-I, DS-PG-1, PG-S1) is a small cellular or pericellular matrix proteoglycan that is closely related in structure to two other small proteoglycans, decorin (PG-II, PG-S2, DS-PG2, or PG-40) and fibromodulin. The core protein is made up predominantly of a series of 11 tandem repeats that appear to have been used throughout evolution for protein-protein, protein-cell, or cell-cell interactions. The function of biglycan is unclear at this time, but it has been shown to bind transforming growth factor beta in vitro. We have cloned and partially sequenced the approximately 8-kilobase pair human biglycan gene. The gene consists of eight exons including one in the sequence that encodes the 5'-untranslated region of the mRNA. The first and seventh introns are approximately 1 kilobase pair, while the remainder are shorter. With the exception of the first two introns, all of the introns are spread throughout the hydrophobic repeat domain. The 500-base pair 5' to the start of transcription contains several elements that strongly suggest that it contains a significant amount of the gene promoter. The elements include one AP2 and five SP1 consensus sequences. Like in many other genes, the biglycan gene promoter lacks both a CAAT and TATA box but is rich in GC content. Using 3H-labeled cDNA and in situ hybridization and autoradiography of human chromosomes, the human gene was localized to the end of the long arm of the X chromosome (Xq27-ter). The relationship of biglycan to a number of other proteins containing the leucine rich repeats is discussed with respect to homologies of cysteine regions immediately adjacent to the repeat sequences. PMID- 1860846 TI - The human myristoylated alanine-rich C kinase substrate (MARCKS) gene (MACS). Analysis of its gene product, promoter, and chromosomal localization. AB - The expression of a major cellular substrate for protein kinase C, the MARCKS protein, is regulated in a cell-, tissue-, and developmental stage-specific fashion; in addition, this expression can be stimulated acutely by various cytokines in certain cell types. We have begun to characterize the human gene in order to elucidate the genetic elements responsible for this highly regulated expression. We first cloned a human MARCKS cDNA, which encoded a predicted protein of 332 amino acids (Mr 31,600) that was approximately 89, 74, and 59% identical to the bovine, mouse, and chicken proteins, respectively. Regions conserved at the amino acid level included the amino-terminal myristoylation consensus sequence, the site of intron splicing, and the phosphorylation site domain. The human cDNA was used to demonstrate that tumor necrosis factor-alpha could rapidly stimulate MARCKS gene transcription in the human promyelocytic leukemia cell line HL60. Genomic clones were then isolated; sequence analysis identified a putative promoter region that had no TATA box and contained multiple transcription initiation sites in a region spanning 57 base pairs (bp). This was followed by a 5'-untranslated region of approximately 400 bp, which displayed a complex predicted secondary structure with a delta G of -73.4 kcal/mol. Plasmid constructions containing between 52 and 1453 bp of the human MARCKS promoter linked to the human growth hormone gene were then used in transient expression experiments. Constructions containing 52 and 110 bp of the MARCKS promoter did not exhibit promoter function while the larger constructions all exhibited promotor function; the 248-bp fragment of the MARCKS promoter was 80% as effective as the human ferritin promoter in stimulating expression of human growth hormone in intact cells. Using an insert from the human genomic clone as a probe, we identified human chromosome 6, q21-qter, as the location of the MARCKS gene; this has been assigned the gene symbol MACS. PMID- 1860847 TI - A peptide corresponding to an export-defective mutant OmpA signal sequence with asparagine in the hydrophobic core is unable to insert into model membranes. AB - We have examined the comparative membrane interaction properties of synthetic peptides corresponding to the wild-type and an export-defective, mutated signal sequence from the Escherichia coli outer membrane protein, OmpA. As part of a collaborative study of the effects of various alterations on the function of the OmpA signal sequence and the biophysical properties of the corresponding synthetic peptides, we incorporated the small, neutral polar residue, asparagine, into the hydrophobic core in place of Ile-8. This seemingly minor perturbation to the signal sequence caused a complete block of export in vivo (J. Goldstein, S. Lehnhardt, and M. Inouye, following paper). We now explore in detail the difference in the properties of the wild-type and the Ile-8----Asn OmpA signal peptides. The fluorescent residue Trp was substituted in both peptides in place of the wild-type Phe at position 15. This mutation is silent phenotypically and provides a superb probe of membrane interaction. We find that the Asn substitution leaves the conformational properties of the signal sequence essentially unchanged, but prevents any significant interaction of the peptide with a lipid bilayer. Asparagines are very underrepresented among known signal sequences. We believe this low frequency to be due to the lowering of mean residue hydrophobicity caused by incorporation of Asn and the consequent reduced ability to bind and insert into membranes. PMID- 1860848 TI - In vivo effect of asparagine in the hydrophobic region of the signal sequence. AB - On the basis of the biophysical studies on the synthetic mutant (Ile-8----Asn) OmpA signal peptide in the preceding paper (Hoyt, D. C., and Gierasch, L.M. (1991) J. Biol. Chem. 266, 14406-14412), the in vivo effects of the same mutation were examined by fusing the mutant OmpA signal sequence to Staphylococcus aureus nuclease or TEM beta-lactamase. The mutation in which the isoleucine residue at position 8 of the OmpA signal sequence of Escherichia coli was replaced with a neutral polar residue, asparagine, resulted in a defective signal peptide. The mutant signal sequence was unable to be processed, and the precursor molecule accumulated in the cytoplasmic as well as in the membrane fractions, indicating that the Ile-8----Asn OmpA signal sequence is not competent for translocating nuclease A or beta-lactamase across the membrane. This result is consistent with the in vitro studies on the Ile-8----Asn OmpA signal peptide, which indicated that the mutant signal peptide was unable to penetrate into the hydrophobic core of the lipid bilayer. Other asparagine or glutamine substitution mutations in the hydrophobic region of the OmpA signal sequence were also examined. Interestingly, the OmpA signal sequence with either Ile-8----Gln, Val-10----Asn, or Leu-12--- Asn mutation was completely defective as the Ile-8----Asn OmpA signal sequence, while the Ile-6----Asn and Ala-9----Asn OmpA nucleases were able to be processed to secrete nuclease, although the processing occurred at a much slower rate than the wild-type OmpA nuclease. These results indicate that the defects depend on the position of the lesion in the hydrophobic core of the OmpA signal sequence. PMID- 1860849 TI - The major colonic cell mitogen extractable from colonic mucosa is an N terminally extended form of basic fibroblast growth factor. AB - Colonic growth factors (CGFs) were extracted from porcine intestinal epithelium and mucosa. Under acidic conditions, very little mitogenic activity (as assayed using murine 3T3 fibroblasts and a human colonic cell line) was extractable. However, by extracting at neutral or slightly alkaline pH, significant mitogenic activity for both the murine fibroblasts and human colonic carcinoma cell line could be detected. CGFs are present throughout the intestine and cecum. The epithelial mucosa of the distal colorectal region appeared to contain mitogens which were more potent for the colonic cells than the 3T3 fibroblasts. Purification of CGFs from the colonic mucosa required removal of associated mucin by pH precipitation prior to chromatographic fractionation. It was then possible to develop a complete purification (390,000-fold) scheme for the major CGF, an 18 kDa protein which bound to heparin-Sepharose. N-terminal sequence analysis yielded a single sequence (Q)SPGGAMAAGSITTLPALP, i.e. an N-terminally extended form of basic fibroblast growth factor. Apart from the substitution of Gly in bovine basic fibroblast growth factor by a Ser in porcine CGF, the proteins are identical. A similar extraction procedure using purified human colonic crypt epithelial cells yielded a mitogen for the human colonic cell line with similar chromatographic properties. PMID- 1860850 TI - Digitonin permeabilization does not affect mitochondrial function and allows the determination of the mitochondrial membrane potential of Trypanosoma cruzi in situ. AB - Digitonin can be used to permeabilize selectively the plasma membrane of Trypanosoma cruzi epimastigotes without significantly affecting the functional integrity of mitochondria. Addition of digitonin at concentrations close to 64 microM caused decrease in the rate of basal respiration of epimastigotes similar to that caused by oligomycin. A further addition of carbonyl cyanide p trifluorophenylhydrazone (FCCP) brought respiration to the same rate observed prior to the inclusion of digitonin or oligomycin. This suggests that like oligomycin, digitonin is shifting respiration to a nonphosphorylating state probably by depleting the cells from adenine nucleotides due to permeabilization of the plasma membrane. The use of low concentrations of digitonin allowed the quantitative determination of the mitochondrial membrane potential of these cells in situ using safranine O. The response of epimastigotes mitochondrial membrane potential to phosphate, FCCP, valinomycin, nigericin, ADP, and Ca2+ indicates that these mitochondria behave similarly to vertebrate mitochondria regarding the properties of their electrochemical proton gradient. In addition, T. cruzi mitochondria are able to build up and retain a membrane potential of a value comparable to that of mammalian mitochondria. The trypanocidal drug crystal violet, as well as other cationic drugs such as dequalinium, induced a rapid dose related collapse of the inner mitochondrial membrane potential. PMID- 1860851 TI - Estimation of standard Gibbs energy changes of biotransformations. AB - Contributions and corrections for the estimation of standard Gibbs energies are given. The group contribution method, applicable to both cyclic and acyclic compounds, permits the approximate estimation of the standard Gibbs energy of a biotransformation, given the stoichiometry and structures of the metabolites involved. Estimated standard Gibbs energies of formation for a number of acyclic biochemical compounds are provided. PMID- 1860852 TI - Free radical-induced carbonyl content in protein of estrogen-treated hamsters assayed by sodium boro[3H]hydride reduction. AB - Oxidative damage to proteins is known to occur via conversion of side chain amino groups to corresponding carbonyl derivatives. Such damage to enzymes and purified proteins has been quantified previously by reduction with sodium boro[3H]hydride and subsequent measurement of the incorporation of 3H into amino acid fractions. In this study, the NaB3H4 reduction assay was modified to permit the quantitation of free radical-mediated oxidative damage to proteins obtained from animals. Modifications included additional extractions of protein isolates with organic solvents to remove lipids and with nitric acid to remove metal ions. The modified assay has first been validated in vitro by measuring changes in levels of oxidative damage to bovine serum albumin exposed to xanthine plus xanthine oxidase (2-fold increase), to hydrogen peroxide and iron(II) sulfate (5-fold increase), or to gamma radiation (30-fold increase over controls, respectively). gamma radiation of isolated hamster kidney protein also raised the carbonyl content in a dose-dependent manner. The modified assay has then been validated in vivo by measuring the changes in oxidative damage to lung tissue in animals exposed to approximately 85% oxygen (2-fold increase) or to different doses of paraquat (5-fold increase with the high dose over controls, respectively). The assay was then used to examine free radical-mediated oxidation introduced by acute or chronic treatment of hamsters with estrogens, since both synthetic and natural estrogens induce kidney tumors in this species. Priming of hamsters for 3 days with 20 mg/kg/day diethylstilbestrol and treatment with 100 mg/kg of this drug on the 4th day resulted in a 160% increase in free radical modification of renal proteins. Oxidative damage to kidney proteins was also assayed in hamsters treated with estradiol implants for up to 7 months, a regimen known to induce kidney tumors. Significant increases in covalent oxidative modification to renal proteins over values in age-matched controls were detected after 1, 2, and 7 months of continuous estradiol exposure. It is concluded that the modification of the NaB3H4 reduction assay is a useful postlabeling method for monitoring free radical action in vivo. Furthermore, it is postulated that free radical damage in estrogen-treated hamster kidney plays a role in estrogen-induced carcinogenesis. PMID- 1860853 TI - Site-directed mutagenesis of a single tryptophan near the middle of the channel forming toxin aerolysin inhibits its transfer across the outer membrane of Aeromonas salmonicida. AB - The channel-forming protein aerolysin must cross both the inner and outer bacterial membranes during its secretion from Aeromonas hydrophila or from Aeromonas salmonicida containing the cloned structural gene. We examined the fate of three mutant proteins in which Trp-227, near the middle of the amino acid chain, was replaced with glycine, leucine, or phenylalanine by site-directed mutagenesis. All three proteins crossed the inner membrane and entered the periplasm in the same way as wild-type, and in each case the signal sequence was removed correctly. Little or none of the proaerolysin substituted with glycine or leucine was released into the culture supernatant. Instead, significant amounts became associated with the outer membrane. The Phe-227 protoxin was secreted by the bacteria but at a reduced rate. The leucine and phenylalanine mutant proteins were purified and compared with native proaerolysin. They were processed correctly to the mature forms by treatment with trypsin, and like native aerolysin, both were resistant to further proteolysis. In each case, processing was followed by the formation of oligomers similar to those produced by native toxin. The hemolytic activity of the processed Phe-227 mutant was one-quarter that of wild-type toxin whereas Leu-227 aerolysin had less than one-hundredth the wild-type activity. These results are further evidence that aerolysin is secreted in at least two steps. As well, they show that the last step, crossing the outer membrane, can be blocked by an apparently small change in the structure of the protein. PMID- 1860854 TI - Lignin peroxidase of Phanerochaete chrysosporium. Evidence for an acidic ionization controlling activity. AB - The active site amino acid residues of lignin peroxidase are homologous to those of other peroxidases; however, in contrast to other peroxidases, no pH dependence is observed for the reaction of ferric lignin peroxidase with H2O2 to form compound I (Andrawis, A., Johnson, K.A., and Tien, M. (1988) J. Biol. Chem. 263, 1195-1198). Chloride binding is used in the present study to investigate this reaction further. Chloride binds to lignin peroxidase at the same site as cyanide and hydrogen peroxide. This is indicated by the following. 1) Chloride competes with cyanide in binding to lignin peroxidase. 2) Chloride is a competitive inhibitor of lignin peroxidase with respect to H2O2. The inhibition constant (Ki) is equal to the dissociation constant (Kd) of chloride at all pH values studied. Chloride binding is pH dependent: chloride binds only to the protonated form of lignin peroxidase. Transient-state kinetic studies demonstrate that chloride inhibits lignin peroxidase compound I formation in a pH-dependent manner with maximum inhibition at low pH. An apparent pKa was calculated at each chloride concentration; the pKa increased as the chloride concentration increased. Extrapolation to zero chloride concentration allowed us to estimate the intrinsic pKa for the ionization in the lignin peroxidase active site. The results reported here provide evidence that an acidic ionizable group (pKa approximately 1) at the active site controls both lignin peroxidase compound I formation and chloride binding. We propose that the mechanism for lignin peroxidase compound I formation is similar to that of other peroxidases in that it requires the deprotonated form of an ionizable group near the active site. PMID- 1860855 TI - The quaternary structure of streptavidin in urea. AB - We report on the interactions of urea and guanidinium salts with streptavidin. Gel filtration chromatography in 0, 4, 6, and 7 M urea indicates that the streptavidin tetramer remains intact in urea. Biotin alters the electrophoretic mobility of streptavidin whether or not 6 M urea is present. The intrinsic fluorescence of streptavidin is increased and blue-shifted in 6 M urea. The fluorescence changes indicate the absence of unfolding. A conformational response to urea is possible, but much of the fluorescence change is due to urea binding as a weak biotin analog (Ka approximately 1.3 M-1). The resistance to structural perturbation by urea reflects the structural stability of streptavidin's anti parallel beta-barrel motif. Unfolding is sluggish in 6 M guanidinium hydrochloride (half-time, approximately 50 days). After guanidinium thiocyanate unfolding, streptavidin can be refolded, but the unfolding and refolding transitions are centered at different concentrations of perturbant. Slow unfolding, with a 15th power dependence on guanidinium thiocyanate concentration, may be partially responsible for the noncoincidence of the unfolding and refolding processes. Nonequilibrium behavior is also seen in 6 M urea, as native streptavidin does not unfold and guanidinium thiocyanate unfolded streptavidin does not refold. Refolding does occur at lower concentrations of urea. Guanidinium thiocyanate only slowly unfolds the biotin-streptavidin complex. In the presence of biotin, unfolded streptavidin does not refold in 6 M guanidinium thiocyanate or in 6 M urea. PMID- 1860856 TI - RpoB8, a rifampicin-resistant termination-proficient RNA polymerase, has an increased Km for purine nucleotides during transcription elongation. AB - The rpoB8 allele of Escherichia coli maps to the beta-subunit of RNA polymerase and confers rifampicin resistance as well as increased termination at both intrinsic and rho-dependent terminators in vivo. This phenotype suggests that the mutant is defective in an enzymatic property of RNA polymerase important for all termination events. We analyzed the in vitro transcription properties of this enzyme to determine the nature of the defect. As compared with the wild-type enzyme, RpoB8 exhibits enhanced pausing and a significant reduction in rate of elongation on natural templates. In addition, RpoB8 RNA polymerase has a 3-5-fold higher Km for purine nucleotides during elongation on synthetic templates. In contrast, both the mutant and wild-type enzyme have the same initiation Km for ATP. Kinetic analysis indicates that RpoB8 is likely to be defective in nucleotide binding during elongation, suggesting that the mutational alteration affects the binding site. We show that our data are consistent with the idea that the altered Km underlies the altered pausing and elongation properties of the enzyme, and we discuss the implication of these results for the termination proficiency of the mutant strain. PMID- 1860857 TI - Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme. AB - Culture materials and grains contaminated with certain isolates of Fusarium moniliforme cause equine leucoencephalomalacia, porcine pulmonary edema syndrome, and liver cancer in rats. The causative agents are thought to be a family of compounds called fumonisins, which bear considerable structural similarity to the long-chain (sphingoid) base backbones of sphingolipids. Incubation of rat hepatocytes with fumonisins inhibited incorporation of [14C]serine into the sphingosine moiety of cellular sphingolipids with an IC50 of 0.1 microM for fumonisin B1. In contrast, fumonisin B1 increased the amount of the biosynthetic intermediate sphinganine, which suggests that fumonisins inhibit the conversion of [14C]sphinganine to N-acyl-[14C]sphinganines, a step that is thought to precede introduction of the 4,5-trans double bond of sphingosine (Merrill, A.H., Jr. and Wang, E. (1986) J. Biol. Chem. 261, 3764-3769). In agreement with this mechanism, fumonisin B1 inhibited the activity of sphingosine N-acyltransferase (ceramide synthase) in rat liver microsomes with 50% inhibition at approximately 0.1 microM and reduced the conversion of [3H]sphingosine to [3H]ceramide by intact hepatocytes. As far as we are aware, this is the first discovery of a naturally occurring inhibitor of this step of sphingolipid metabolism. These findings suggest that disruption of the de novo pathway of sphingolipid biosynthesis may be a critical event in the diseases that have been associated with consumption of fumonisins. PMID- 1860858 TI - Oxidized low density lipoprotein is resistant to cathepsins and accumulates within macrophages. AB - The rate of uptake of oxidized low density lipoprotein (LDL) by mouse peritoneal macrophages is similar to that of acetyl LDL; but only approximately 50% of the internalized oxidized LDL is ultimately degraded, in contrast to the near complete degradation seen with acetyl LDL. The objectives of this study were to determine if this was due to increased surface binding of oxidized LDL, different uptake pathways for oxidized LDL and acetyl LDL, lysosomal dysfunction caused by oxidized LDL, or resistance of oxidized LDL to hydrolysis by lysosomal proteinases. LDL binding studies at 4 degrees C showed that the increased cell association with oxidized LDL could not be explained by differences in cell surface binding. Immunofluorescence microscopy confirmed intracellular accumulation of apoB-immunoreactive material in macrophages incubated with oxidized LDL, but not with acetyl LDL. The scavenger receptor ligand polyinosinic acid inhibited both the cell association and degradation of oxidized LDL in macrophages by greater than 75%, suggesting a common uptake pathway for degraded LDL and nondegraded LDL. Studies in THP-1 cells also did not reveal more than one specific uptake pathway for oxidized LDL. LDL derivatized by incubation with oxidized arachidonic acid (under conditions that prevented oxidation of the LDL itself) showed inefficient degradation, similar to oxidized LDL. When macrophages were incubated with oxidized LDL together with acetyl 125I-LDL, the acetyl LDL was degraded normally, excluding lysosomal dysfunction as the explanation for the accumulation of oxidized LDL. Generation of trichloroacetic acid-soluble products from oxidized 125I-LDL by exposure to cathepsins B and D was less than that observed with native 125I-LDL. LDL modified by exposure to reactive products derived from oxidized arachidonic acid was also degraded more slowly than native 125I-LDL by cathepsins. In contrast, acetyl 125I-LDL was degraded more rapidly by cathepsins than native 125I-LDL, and aggregated LDL and malondialdehyde-modified LDL were degraded at the same rate as native 125I-LDL. It is concluded that the intracellular accumulation of oxidized LDL in macrophages can be explained at least in part by the resistance of oxidatively modified apolipoprotein B to cathepsins. This resistance to cathepsins does not appear to be due to aggregation of oxidized LDL, but may be a consequence of modification of apolipoprotein B by lipid peroxidation products. PMID- 1860859 TI - ATP-dependent regulation of rabbit myocardial cytosolic calcium-independent phospholipase A2. AB - We report here that rabbit myocardial cytosolic calcium-independent phospholipase A2 exists as a high molecular weight complex comprised of catalytic and regulatory polypeptides whose activity and stability are influenced by specific interactions with ATP. Multiple lines of evidence document the functional significance of interactions between the catalytic complex and ATP including: 1) adenine nucleotide triphosphates attenuate the rate of thermal denaturation of native cytosolic phospholipase A2; 2) ATP augments the initial rate of phospholipid hydrolysis in a manner independent of the concentration, interfacial properties, and physical state of aggregated substrate; 3) adenine nucleotide triphosphates attenuate the reactivity of an essential thiol residue to covalent modification by 5,5'-dithiobis(2-nitrobenzoic acid); and 4) the catalytic complex specifically and reversibly binds to ATP affinity matrices, although the purified 40-kDa catalytic subunit neither binds to ATP affinity matrices nor is subject to ATP-dependent activation and stabilization. The catalytic and regulatory elements were functionally resolved by differential thermal inactivation and the ATP regulatable phospholipase A2 catalytic complex was reassembled by reconstitution of highly purified catalytic and partially purified regulatory proteins. Thus, alterations in ATP concentration influence the activity and longevity of the myocardial cytosolic calcium-independent phospholipase A2 catalytic complex, thereby potentially modulating the release of lipidic second messengers and facilitating adaptive alterations in membrane physical properties. PMID- 1860860 TI - Analysis of retroviral protease cleavage sites reveals two types of cleavage sites and the structural requirements of the P1 amino acid. AB - Retroviruses encode a protease which cleaves the viral Gag and Gag/Pol protein precursors into mature products. To understand the target sequence specificity of the viral protease, the amino acid sequences from 46 known processing sites from 10 diverse retroviruses were compared. Sequence preference was evident in positions P4 through P3' when compared to flanking sequences. Approximately 80% of all cleavage site sequences could be grouped into two classes based on the sequence composition flanking the scissile bond. The sequences at the amino terminal cleavage site of the major capsid protein of Gag is always a member of one of the two classes while the carboxyl-terminal cleavage site is of the other class, suggesting a biological role for the two classes. Known processing site sequences proved useful in a motif searching strategy to identify processing sites in retroviral protein sequences, particularly in Gag. In all known cleavage sites, the P1 amino acid is hydrophobic and unbranched at the beta-carbon. The sequence requirements of the P1 position were tested by site-directed mutagenesis of the P1 Phe codon in an HIV-1 Pol cleavage site. Mutations were tested for protease-mediated cleavage of the Pol precursor expressed in Escherichia coli. PMID- 1860861 TI - A cumulative specificity model for proteases from human immunodeficiency virus types 1 and 2, inferred from statistical analysis of an extended substrate data base. AB - Statistical analysis of an expanded data base of regions in viral polyproteins and in non-viral proteins that are sensitive to hydrolysis by the protease from human immunodeficiency virus (HIV) type 1 has generated a model which characterizes the substrate specificity of this retroviral enzyme. The model leads to an algorithm for predicting protease-susceptible sites from primary structure. Amino acids in each of the sites from P4 to P4' are tabulated for 40 protein substrates, and the frequency of occurrence for each residue is compared to the natural abundance of that amino acid in a selected data set of globular proteins. The results suggest that the highest stringency for particular amino acid residues is at the P2, P1, and P2' positions of the substrate. The broad specificity of the HIV-1 protease appears to be a consequence of its being able to bind productively substrates in which interactions with only a few Pi or Pi' side-chains need be optimized. The analysis, extended to 22 protein segments cleaved by the HIV-2 protease, delineates marked differences in specificity from that of the HIV-1 enzyme. PMID- 1860862 TI - Purification, gene cloning, and sequence analysis of an L-isoaspartyl protein carboxyl methyltransferase from Escherichia coli. AB - Mammalian tissues contain protein carboxyl methyltransferases that catalyze the transfer of methyl groups from S-adenosylmethionine to the free carboxyl groups of D-aspartyl or L-isoaspartyl residues (EC 2.1.1.77). These enzymes have been postulated to play a role in the repair and/or degradation of spontaneously damaged proteins. We have now characterized a similar activity from Escherichia coli that recognizes L-isoaspartyl-containing peptides as well as protein substrates such as ovalbumin. The enzyme was purified by DEAE-cellulose, hydroxylapatite, Sephadex G-100, polyaspartate, and reversed-phase chromatography and was shown to consist of a single 24-kDa polypeptide chain. The sequence determined for the N-terminal 39 residues was used to design an oligonucleotide probe that allowed the precise localization of its structural gene (pcm) on the physical map of the E. coli chromosome at 59 min. Transformation of E. coli cells with a plasmid containing DNA from this region results in a 3-4-fold overproduction of enzyme activity. The nucleotide sequence determined for the pcm gene and its flanking regions was used to deduce a mature amino acid sequence of 207 residues with a calculated molecular weight of 23,128. This sequence shows 30.8% sequence identity with the human L-isoaspartyl/D-aspartyl methyltransferase and suggests that this enzyme catalyzes a fundamental reaction in both procaryotic and eucaryotic cells. PMID- 1860863 TI - Structure and membrane topology of TAPA-1. AB - TAPA-1 (the target of an antiproliferative antibody) is a 26-kDa cell surface protein expressed on most human cell lines. TAPA-1 is a member of an evolutionarily related family of cell surface proteins all of which contain four transmembrane domains. A model is proposed for topology of TAPA-1 based on proteolysis studies in the in vitro translated protein embedded into microsomal membranes. This analysis predicts that the amino and the carboxyl termini of the molecule are cytoplasmic and that the two hydrophilic regions of the molecule are extracellular. The antigenic epitope of the human TAPA-1 is contained within a subregion of the second extracellular domain of the protein. This is the only region in the protein that has not been tightly conserved in mammalian evolution. PMID- 1860864 TI - Sequence dependence of protein isoprenylation. AB - Several proteins have been shown to be post-translationally modified on a specific C-terminal cysteine residue by either of two isoprenoid biosynthetic pathway metabolites, farnesyl diphosphate or geranylgeranyl diphosphate. Three enzymes responsible for protein isoprenylation were resolved chromatographically from the cytosolic fraction of bovine brain: a farnesyl-protein transferase (FTase), which modified the cell-transforming Ras protein, and two geranyl geranyl-protein transferases, one (GGTase-I) which modified a chimeric Ras having the C-terminal amino acid sequence of the gamma-6 subunit of heterotrimeric GTP binding proteins, and the other (GGTase-II) which modified the Saccharomyces cerevisiae secretory GTPase protein YPT1. In a S. cerevisiae strain lacking FTase activity (ram1), both GGTases were detected at wild-type levels. In a ram2 S. cerevisiae strain devoid of FTase activity, GGTase-I activity was reduced by 67%, suggesting that GGTase-I and FTase activities derive from different enzymes but may share a common genetic feature. For the FTase and the GGTase-I activities, the C-terminal amino acid sequence of the protein substrate, the CAAX box, appeared to contain all the critical determinants for interaction with the transferase. In fact, tetrapeptides with amino acid sequences identical to the C terminal sequences of the protein substrates for FTase or GGTase-I competed for protein isoprenylation by acting as alternative substrates. Changes in the CAAX amino acid sequence of protein substrates markedly altered their ability to serve as substrates for both FTase and GGTase-I. In addition, it appeared that FTase and GGTase-I had complementary affinities for CAAX protein substrates; that is, CAAX proteins that were good substrates for FTase were, in general, poor substrates for GGTase-I, and vice versa. In particular, a leucine residue at the C terminus influenced whether a CAAX protein was either farnesylated or geranylgeranylated preferentially. The YPT1 C terminus peptide, TGGGCC, did not compete or serve as a substrate for GGTase-II, indicating that the interaction between GGTase-II and YPT1 appeared to depend on more than the 6 C-terminal residues of the protein substrate sequence. These results identify three different isoprenyl-protein transferases that are each selective for their isoprenoid and protein substrates. PMID- 1860865 TI - Purification, characterization, and studies on biosynthesis of a 59-kDa bone sialic acid-containing protein (BSP) from rat mandible using a monoclonal antibody. Evidence that 59-kDa BSP may be the rat counterpart of human alpha 2-HS glycoprotein and is synthesized by both hepatocytes and osteoblasts. AB - A monoclonal antibody was raised against a mineralized tissue-specific sialoprotein containing no phosphorus using partially purified noncollagenous bone matrix proteins from rats as antigen. Then the sialoprotein was purified by high performance liquid chromatography from rat mandibulae using the monoclonal antibody as a marker. The sialoprotein (59-kDa bone sialoprotein (BSP)) with a molecular weight of 59,000 contained 1.4% sialic acid but no detectable phosphorus. Immunohistochemical studies with the antibody showed that the protein was specific to mineralized tissues such as bone and dentin, and present in osteoblasts, osteocytes, and bone matrix. No other soft tissues, such as the cartilage, liver, kidney, and periosteum, were stained. However, Western blot analysis showed that plasma contained immunoreactive 59-kDa BSP. The quantitative amino acid composition of 59-kDa BSP resembled that of human alpha 2-HS glycoprotein (alpha 2-HSG) (Lee, C.-C., Bowman, B.H., and Yang, F. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 4403-4407; Kellermann, J., Haupt, H., Auerswald, E. A., and Muller-Esterl, W. (1989) J. Biol. Chem. 264, 14121-14128) and rat 64-kDa protein (Franzen, A., and Heinegard, D. (1985) in The Chemistry and Biology of Mineralized Tissues (Butler, W.T., ed), p. 132, EBSCO Media, Birmingham, AL). Amino acid sequence analyses of the amino-terminal region and four peptide fragments of 59-kDa BSP revealed that about 50% of the amino acids were homologous with those of human alpha 2-HSG, which is known to be synthesized by the liver, transported in the bloodstream, and incorporated into calcified tissues. But when newborn rat calvaria, primary cultures of osteoblast-rich cells, and adult rat hepatocytes were incubated with radioactive leucine, immunoreactive 59-kDa BSP was detected in their conditioned medium by fluorography. Several characteristics, including the amino acid sequence, suggest that 59-kDa BSP may be the rat counterpart of human alpha 2-HSG. However, rat 59 kDa BSP is a single peptide and synthesized by both osteoblasts and hepatocytes, whereas human alpha 2-HSG is known to be a heterodimer and to be synthesized by the liver. PMID- 1860866 TI - A 48-kDa, S-antigen-like phosphoprotein in yeast DNA-replicative complex preparations. AB - A 48-kDa protein from the budding yeast Saccharomyces cerevisiae is antigenically and structurally similar to S-antigen from retina. Eight anti-S-antigen monoclonal antibodies, directed against distinct epitopes, cross-reacted with a yeast 48-kDa protein. Structural similarity between the bovine and yeast proteins was further demonstrated by comparison of tryptic peptide fragments containing one of these epitopes. This 48-kDa yeast protein appears to be a component of the replicative complex of the cell. It was found associated with immunoaffinity purified yeast DNA polymerase I-primase and with yeast DNA-replicative complex. The 48-kDa protein was phosphorylated by a protein kinase activity endogenous to the replicative complex preparation. This phosphorylation was dependent on the cell division cycle gene CDC7. In addition, authentic bovine S-antigen, when added to yeast DNA polymerase I-primase, stimulated polymerase activity. These findings suggest that the yeast S-antigen-like protein may play a role in replication, and they raise the possibility that it may be involved in traversal of the G1/S boundary of the cell cycle. PMID- 1860867 TI - Structural organization and chromosomal localization of the gene for the E1 beta subunit of human branched chain alpha-keto acid dehydrogenase. AB - A defect in the E1 beta subunit of the branched chain alpha-keto acid dehydrogenase (BCKDH) complex is one cause of maple syrup urine disease (MSUD). In an attempt to elucidate the molecular basis of MSUD, we isolated and characterized the cDNA of the E1 beta subunit of BCKDH. Using the cDNA as a probe, a chromosomal gene related to E1 beta subunit of human BCKDH was isolated from human gene libraries. The gene of E1 beta subunit is over 100 kilobases long and is split into 10 exons. All of the splice donor and acceptor sites conform to the GT/AG rule. The transcription initiation site was determined by nuclease S1 mapping and primer extension and was located 47 bases upstream from the initiation codon. A "CAAT" box and its reverse complement sequences were present at 39 bases and 75 bases upstream from the cap site, but there was no "TATA" box like sequence. There were three sets of sequences resembling the transcription factor Sp1-binding sites and two sets of sequences resembling the enhancer core sequence. We also analyzed the chromosomal localization of the gene for the E1 beta subunit of BCKDH. The gene was mapped to chromosome 6. Knowledge of the gene structure of human BCKDH E1 beta subunit will facilitate further studies on the expression and regulation of this gene and provide necessary information for analyses of mutations in patients with MSUD. PMID- 1860868 TI - Characterization of an adult muscle acetylcholine receptor subunit by expression in fibroblasts. AB - To study the functional and structural roles of the epsilon subunit in adult muscle acetylcholine receptor (AChR), we have co-expressed the alpha and epsilon subunits of the mouse receptor in transfected fibroblasts. Ligand binding studies suggest that association of epsilon with alpha subunit results in a lower association rate constant for 125I-labeled alpha-bungarotoxin binding than that of the unassembled alpha subunit, approaching that for toxin binding to the AChR. Furthermore, alpha epsilon complexes contain high affinity binding sites for competitive antagonists and agonists not present in the unassembled alpha subunit, but similar to one of the two nonequivalent binding sites in the adult AChR. Structural analysis of alpha epsilon complexes by sucrose gradient velocity centrifugation suggests that some of the complexes formed are trimers or tetramers of alpha and epsilon subunits. Comparison of these data with those previously obtained for alpha gamma complexes suggests that gamma and epsilon have homologous functional roles and identical structural positions in the fetal and adult AChRs, respectively. PMID- 1860869 TI - Granzyme A binding to target cell proteins. Granzyme A binds to and cleaves nucleolin in vitro. AB - The physiologic substrates of cytotoxic T lymphocyte granule-associated serine esterases (referred to hereafter as proteases or "granzymes"), and the role of these enzymes in cell-mediated activity remain unclear. We have developed an assay for possible ligands of the trypsin-like dimeric serine protease granzyme A based on Western immunoblotting techniques. This protein-binding assay demonstrates the selective binding of granzyme A to several proteins present in the target cell P815. The binding specificity is preserved when enzyme binding is performed in the presence of excess competing proteins, including such cationic species as lysozyme and RNase. Enzyme binding is inhibited, however, by heat or detergent inactivation of granzyme A. Subcellular fractionation of target cells shows that the nuclear fraction contains most granzyme A binding reactivity, which is recovered in the nuclear salt wash fraction. A protein with Mr = 100,000 and two closely migrating proteins with Mr = 35,000 and 38,000 are the predominant reactive moieties, and the N-terminal sequence of the 100-kDa protein confirmed that this protein was murine nucleolin. Incubation of granzyme A with nucleolin generates a discrete proteolytic cleavage product of Mr = 88,000. Since nucleolin is known to shuttle between nucleus and cytoplasm, the interaction of granzyme A and nucleolin may be important in the process of apoptosis which accompanies cytotoxic T lymphocyte-mediated lysis of target cells. PMID- 1860870 TI - Identification of the phosphorylation sites of the murine small heat shock protein hsp25. AB - Native phosphorylated mouse small heat shock protein hsp25 from Ehrlich ascites tumor cells was isolated and the in vivo phosphorylation sites of the protein were determined. Furthermore, native hsp25 was phosphorylated by the endogenous kinase(s) in a cell-free system as well as recombinant hsp25 was phosphorylated in vitro by protein kinase C and catalytic subunit of cAMP-dependent protein kinase. The two major phosphorylation sites of native and recombinant hsp25 were determined as Ser-15 and Ser-86. There are no differences in the hsp25 phosphorylation sites phosphorylated by the protein kinase C, the catalytic subunit of cAMP-dependent protein kinase and the unknown intracellular kinase(s). The serine residues identified exist in all known small mammalian stress proteins and are located in the conserved kinase recognition sequence Arg-X-X-Ser. PMID- 1860871 TI - Extraction and nutritional/hormonal regulation of tissue insulin-like growth factor 1 activity. AB - Studies of insulin-like growth factor 1 (IGF-1) mRNA translation products suggest synthesis as a high Mr precursor, larger than circulating forms. To search for a precursor, we characterized IGF-1 immunoreactivity and IGF bioactivity in extracts from the liver and other body tissues. Sequential extraction with neutral followed by acid buffer was superior to extraction with acid/ethanol or acid alone in yield of immunoreactivity and specific activity. Extracts of normal rat liver exhibited both immuno- and bioactivity parallel to that of recombinant IGF-1 and serum IGFs over a 25-fold concentration range. Based on immunoreactivity, the liver of a 134-g rat appears to contain 1.2 micrograms of IGF-1 equivalents, 50% of the 2.45 micrograms in the circulation. Diaphragm, spleen, and kidney contained no significant IGF bioactivity and 8, 17, and 32% of the IGF-1 immunoreactivity of normal liver, respectively. Although serum IGFs were found at 7.5 kDa after size exclusion chromatography at pH 3, hepatic extracts contained a predominant peak of immuno- and bioactivity of apparent molecular mass of 30-35 kDa; both sizes were present in liver perfusates. Both immunoaffinity chromatography followed by Western blotting and IGF-binding protein affinity chromatography followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two predominant species, at 18-19 and 12 kDa. The 18 19-kDa species is consistent with the apparent size of the glycosylated propeptide encoded by IGF-1A mRNA, while the 12-kDa species may be nonglycosylated propeptide. Extract activity was pituitary-dependent; the livers of hypophysectomized rats contained 15.4 and 48.8% of normal immuno- and bioactivity, respectively. During fasting and refeeding of rats, fluctuations in hepatic extract IGF-1 immunoreactivity generally paralleled changes in serum IGF 1 (r = 0.93, p less than 0.001). These studies demonstrate that the liver contains a pituitary- and nutrition-dependent, high Mr form of IGF-1 with immunological and biological properties similar to circulating IGF-1. Processing of this 18-19-kDa molecule through a 12-kDa intermediate may contribute IGF-1 to the circulation. PMID- 1860872 TI - Protein kinase C induces phosphorylation and desensitization of the human 5-HT1A receptor. AB - The effects of short-term phorbol ester treatment of CHO cells that stably express 900 fmol of recombinant human serotonin 5-HT1A receptor/mg of protein on coupling to the inhibition of adenylyl cyclase and on phosphorylation of the receptor were studied. Pretreatment of cell monolayers with phorbol 12-myristate 13-acetate (PMA) caused a dose- and time-dependent shift of the half-maximal dose of serotonin (5-HT) required to inhibit membrane adenylyl cyclase (from IC50 approximately 100 nM to approximately 400 nM). This desensitization (shift in IC50) was rapid, occurring with 5 min of pretreatment and being maximal by 10-15 min; it was also dose-dependent, being half-maximal at approximately 300 nM PMA. Desensitization was also induced by sn-dioctanoylglycerol (DiC8) and blocked by the protein kinase C (PKC) inhibitors sphingosine and 1-(5-isoquinolinesulfonyl) 2-methylpiperazine (H-7). In detached permeabilized cells, PMA pretreatment caused a rapid phosphorylation of immunoprecipitated 5-HT1A receptors, with an approximately 3-4-fold increase that was maximal after 15 min and persisted for 90 min. The phosphorylation occurred at a similar dose of PMA as that which induced desensitization (half-maximal at approximately 300 nM, maximal at 500 nM to 1 microM), could be reproduced by pretreatment with the PKC activators DiC8 or phorbol 12,13-dibutyrate (PDBu), and could be blocked by the PKC inhibitors sphingosine or H-7. The stoichiometry of the phosphorylation was approximately 2 mol of [32P]ATP/mol of receptor, suggesting the involvement at least two of three putative PKC sites within the 5-HT1A receptor. The close concordance between the PKC-induced desensitization and phosphorylation suggests a potential causative link between these two effects of PKC on the human 5-HT1A receptor. PMID- 1860873 TI - Purification and partial characterization of fibrillin, a cysteine-rich structural component of connective tissue microfibrils. AB - Fibrillin, a connective tissue macromolecule (Mr = 350,000) which is normally insoluble in its tissue form, has been purified from the medium of human skin fibroblast and ligament cells in culture. Analysis of the amino acid composition indicates that fibrillin contains approximately 14% cysteine, of which one-third appears to be in the free reactive sulfhydryl form. Electron microscopic images of fibrillin reveal an extended, flexible molecule approximately 148 nm long and 2.2 nm wide. These length measurements are consistent with shape calculations based upon velocity sedimentation data. It is likely that the material we have purified from cell culture medium represents monomeric fibrillin consisting of a single polypeptide chain. Additional ultrastructural immunohistochemical data presented here suggest a model for the parallel, head-to-tail alignment of fibrillin molecules in microfibrils. PMID- 1860874 TI - Refined x-ray structure of papain.E-64-c complex at 2.1-A resolution. AB - E-64-c, a synthetic cysteine protease inhibitor designed from E-64, binds to papain through a thioether covalent bond. The x-ray diffraction data for 2.1-A resolution were used to determine the three-dimensional structure of this complex and refined it to R = 0.159. 0.159. In the complex structure, the configurational conversion from S to R took place on the epoxy carbon of E-64-c, implying that the nucleophilic attack of the Cys-25 thiol group occurs at the opposite side of the epoxy oxygen atom. The leucyl and isoamylamide groups of E-64-c were strongly fixed to papain S subsites by specific interactions, including hydrogen bonding to the Gly-66 residue. The carboxyl-terminal anion of E-64-c formed an electrostatic interaction with the protonated His-159 imidazole ring (O-...HN+ = 3.76 A) and consequently prevented the participation of this residue in the hydrolytic charge-relay system. No significant distortion caused by the binding of E-64-c was shown in the secondary structure of papain. It is important to note that inhibitor and substrate have opposite binding modes for the peptide groups. The possible relationship between the binding mode and inhibitory activity is discussed on the basis of the crystal structure of this complex. PMID- 1860875 TI - Immunological demonstration of a calcium-unresponsive protein kinase C of the delta-type in different species and murine tissues. Predominance in epidermis. AB - An antiserum raised against a delta-protein kinase C (delta-PKC)-specific peptide recognized the purified calcium-unresponsive 76-kDa protein kinase of porcine spleen in the native and the denatured form. This antiserum was used to demonstrate the delta-PKC-like enzyme in spleen of different species, in various cell types and in murine tissues by immunoblotting of the respective extracts. Due to species differences, delta-PKC-like kinases with slightly different molecular weights were observed. The enzyme was found to be present in primary murine keratinocytes, primary bovine endothelial cells, and many cell lines originating from human, rat, and murine tissues. It was present also in all murine tissues tested, predominantly in epidermis, uterus, placenta, lung, brain, spleen, and kidney. In contrast to the conventional alpha, beta, gamma-PKC, it was located almost exclusively in the particulate fraction. The delta-like PKC could be demonstrated in the epidermis and brain of newborn mice, and in both tissues its concentration increased dramatically between day 7 and 14 after birth. The delta-PKC-like kinase of mouse epidermis (p82-kinase) was down regulated after topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin. The amount of the enzyme decreased to less than 20% of the controls within 16 h and recovered almost completely within 72 h after TPA. The existence of the delta-PKC-like kinase in mouse skin, papillomas, and carcinomas could also be demonstrated by immunocytochemical staining of the respective sections. The enzyme was observed predominantly in epithelial layers. A remarkable immunostaining of nuclei in skin sections disappeared after TPA treatment of the animals. PMID- 1860876 TI - Alterations in barley ribulose-1,5-bisphosphate carboxylase/oxygenase activase gene expression during development and in response to illumination. AB - Two genes encode Rbu-P2-carboxylase activase in barley (RcaA and RcaB): RcaA encodes polypeptides of 46 and 42 kDa, which are generated by the alternatively spliced RcaA1 and RcaA2 mRNAs, respectively; RcaB encodes a 42-kDa polypeptide (Rundle, S. J., and Zielinski, R. E. (1991) J. Biol. Chem. 266, 4677-4685). In the cellular differentiation gradient of the first leaf of barley, the three Rca mRNAs accumulate differentially. RcaA1 and A2 mRNAs accumulate predominantly in the mature, most photosynthetically active regions of the leaf in a pattern that parallels accumulation of total Rbu-P2-carboxylase activase protein. However, the kinetics of accumulation of RcaA1 and RcaA2 mRNA differ slightly, indicating that either changes in RcaA pre-mRNA splicing or mRNA turnover occur during development. RcaB mRNA, in contrast, accumulates in the youngest and oldest cell populations at the base and tip of the leaf, respectively. In the mid-region of the leaf, the difference in accumulation between RcaA and RcaB mRNAs is largely attributable to differences in the rates of transcription of the two Rca genes. In this region of the leaf, the three Rca mRNAs accumulate differentially throughout the course of the diurnal cycle. Steady state levels of the three Rca mRNA species increase in parallel in response to increasing irradiance; these changes were accompanied by increased Rbu-P2-carboxylase activase protein accumulation. PMID- 1860877 TI - Structure of a dermatan sulfate hexasaccharide that binds to heparin cofactor II with high affinity. PMID- 1860878 TI - A single amino acid change in the cytoplasmic domain alters the polarized delivery of influenza virus hemagglutinin. AB - In the polarized kidney cell line MDCK, the influenza virus hemagglutinin (HA) has been well characterized as a model for apically sorted membrane glycoproteins. Previous work from our laboratory has shown that a single amino acid change in the cytoplasmic sequence of HA converts it from a protein that is excluded from coated pits to one that is efficiently internalized. Using trypsin or antibodies to mark protein on the surface, we have shown in MDCK cells that HA containing this mutation is no longer transported to the apical surface but instead is delivered directly to the basolateral plasma membrane. We propose that a cytoplasmic feature similar to an endocytosis signal can cause exclusive basolateral delivery. PMID- 1860879 TI - Yeast cell cycle protein CDC48p shows full-length homology to the mammalian protein VCP and is a member of a protein family involved in secretion, peroxisome formation, and gene expression. AB - Yeast mutants of cell cycle gene cdc48-1 arrest as large budded cells with microtubules spreading aberrantly throughout the cytoplasm from a single spindle plaque. The gene was cloned and disruption proved it to be essential. The CDC48 sequence encodes a protein of 92 kD that has an internal duplication of 200 amino acids and includes a nucleotide binding consensus sequence. Vertebrate VCP has a 70% identity over the entire length of the protein. Yeast Sec18p and mammalian N ethylmaleimide-sensitive fusion protein, which are involved in intracellular transport, yeast Pas1p, which is essential for peroxisome assembly, and mammalian TBP-1, which influences HIV gene expression, are 40% identical in the duplicated region. Antibodies against CDC48 recognize a yeast protein of apparently 115 kD and a mammalian protein of 100 kD. Both proteins are bound loosely to components of the microsomal fraction as described for Sec18p and N-ethylmaleimide-sensitive fusion protein. This similarity suggests that CDC48p participates in a cell cycle function related to that of N-ethylmaleimide-sensitive fusion protein/Sec18p in Golgi transport. PMID- 1860880 TI - Muscle cell attachment in Caenorhabditis elegans. AB - In the nematode Caenorhabditis elegans, the body wall muscles exert their force on the cuticle to generate locomotion. Interposed between the muscle cells and the cuticle are a basement membrane and a thin hypodermal cell. The latter contains bundles of filaments attached to dense plaques in the hypodermal cell membranes, which together we have called a fibrous organelle. In an effort to define the chain of molecules that anchor the muscle cells to the cuticle we have isolated five mAbs using preparations enriched in these components. Two antibodies define a 200-kD muscle antigen likely to be part of the basement membrane at the muscle/hypodermal interface. Three other antibodies probably identify elements of the fibrous organelles in the adjacent hypodermis. The mAb IFA, which reacts with mammalian intermediate filaments, also recognizes these structures. We suggest that the components recognized by these antibodies are likely to be involved in the transmission of tension from the muscle cell to the cuticle. PMID- 1860881 TI - Surface extensions of 3T3 cells towards distant infrared light sources. AB - Using a specially designed phase-contrast light microscope with an infrared spot illuminator we found that approximately 25% of 3T3 cells were able to extend pseudopodia towards single microscopic infrared light sources nearby. If the cells were offered a pair of such light sources next to each other, 47% of the cells extended towards them. In the latter case 30% of the responding cells extended separate pseudopodia towards each individual light source of a pair. The strongest responses were observed if the infrared light sources emitted light of wavelengths in the range of 800-900 nm intermittently at rates of 30-60 pulses per min. The temperature increases of the irradiated spots can be shown to be negligible. The results suggest that the cells are able to sense specific infrared wavelengths and to determine the direction of individual sources. PMID- 1860882 TI - Control of actin polymerization in live and permeabilized fibroblasts. AB - We have investigated the spatial control of actin polymerization in fibroblasts using rhodamine-labeled muscle actin in; (a) microinjection experiments to follow actin dynamics in intact cells, and (b) incubation with permeabilized cells to study incorporation sites. Rhodamine-actin was microinjected into NIH-3T3 cells which were then fixed and stained with fluorescein-phalloidin to visualize total actin filaments. The incorporation of newly polymerized actin was assayed using rhodamine/fluorescein ratio-imaging. The results indicated initial incorporation of the injected actin near the tip and subsequent transport towards the base of lamellipodia at rates greater than 4.5 microns/min. Furthermore, both fluorescein and rhodamine-intensity profiles across lamellipodia revealed a decreasing density of actin filaments from tip to base. From this observation and the presence of centripetal flux of polymerized actin we infer that the actin cytoskeleton partially disassembles before it reaches the base of the lamellipodium. In permeabilized cells we found that, in agreement with the injection studies, rhodamine-actin incorporated predominantly in a narrow strip of less than 1-microns wide, located at the tip of lamellipodia. The critical concentration for the rhodamine-actin incorporation (0.15 microM) and its inhibition by CapZ, a barbed-end capping protein, indicated that the nucleation sites for actin polymerization most likely consist of free barbed ends of actin filaments. Because any potential monomer-sequestering system is bypassed by addition of exogenous rhodamine-actin to the permeabilized cells, these observations indicate that the localization of actin incorporation in intact cells is determined, at least in part, by the presence of specific elongation and/or nucleation sites at the tips of lamellipodia and not solely by localized desequestration of subunits. We propose that the availability of the incorporation sites at the tips of lamellipodia is because of capping activities which preferentially inhibit barbed-end incorporation elsewhere in the cell, but leave barbed ends at the tips of lamellipodia free to add subunits. PMID- 1860883 TI - Studies concerning the temporal and genetic control of cell polarity in Saccharomyces cerevisiae. AB - The establishment of cell polarity was examined in the budding yeast, S. cerevisiae. The distribution of a polarized protein, the SPA2 protein, was followed throughout the yeast cell cycle using synchronized cells and cdc mutants. The SPA2 protein localizes to a patch at the presumptive bud site of G1 cells. Later it concentrates at the bud tip in budded cells. At cytokinesis, the SPA2 protein is at the neck between the mother and daughter cells. Analysis of unbudded haploid cells has suggested a series of events that occurs during G1. The SPA2 patch is established very early in G1, while the spindle pole body residues on the distal side of the nucleus. Later, microtubules emanating from the spindle pole body intersect the SPA2 crescent, and the nucleus probably rotates towards the SPA2 patch. By middle G1, most cells contain the SPB on the side of the nucleus proximal to the SPA2 patch, and a long extranuclear microtubule bundle intersects this patch. We suggest that a microtubule capture site exists in the SPA2 staining region that stabilizes the long microtubule bundle; this capture site may be responsible for rotation of the nucleus. Cells containing a polarized distribution of the SPA2 protein also possess a polarized distribution of actin spots in the same region, although the actin staining is much more diffuse. Moreover, cdc4 mutants, which form multiple buds at the restrictive temperature, exhibit simultaneous staining of the SPA2 protein and actin spots in a subset of the bud tips. spa2 mutants contain a polarized distribution of actin spots, and act1-1 and act1-2 mutants often contain a polarized distribution of the SPA2 protein suggesting that the SPA2 protein is not required for localization of the actin spots and the actin spots are not required for localization of the SPA2 protein. cdc24 mutants, which fail to form buds at the restrictive temperature, fail to exhibit polarized localization of the SPA2 protein and actin spots, indicating that the CDC24 protein is directly or indirectly responsible for controlling the polarity of these proteins. Based on the cell cycle distribution of the SPA2 protein, a "cytokinesis tag" model is proposed to explain the mechanism of the non-random positioning of bud sites in haploid yeast cells. PMID- 1860884 TI - A negative feedback loop attenuates EGF-induced morphological changes. AB - Activation of the EGF receptor tyrosine kinase by ligand indirectly activates a series of other cellular enzymes, including protein kinase C. To test the hypothesis that phosphorylation of the EGF receptor by protein kinase C provides an intracellular negative feedback loop to attenuate EGF receptor signaling, we used scanning EM to follow the characteristic EGF-induced retraction of lamellipodia and concomitant cell shape changes. Wild type and mutant EGF receptors were expressed in receptor-deficient NR6 cells. The mutant receptors were prepared by truncation at C' terminal residue 973 (c'973) to provide resistance to ligand-induced down regulation that strongly attenuates receptor signaling and by replacement of threonine 654 (T654) with alanine (A654) to remove the site of phosphorylation by protein kinase C. Cells expressing WT and c'973 EGF receptors demonstrated characteristic lamellipodial retraction after exposure to EGF, with the non-down regulating c'973 EGF receptors responding more rapidly. Exposure of cells to TPA blocked this response. Replacement of T654 by alanine resulted in EGF receptors that were resistant to TPA. Cells expressing the A654 mutation underwent more rapid and more extensive morphologic changes than cells with the corresponding T654 EGF receptor. In cells expressing T654 EGF receptors, down regulation of protein kinase C resulted in more rapid and extensive EGF-induced changes similar to those seen in cells expressing A654 EGF receptors. These data indicate that activation of protein kinase C and subsequent phosphorylation of the EGF receptor at T654 lead to rapid physiological attenuation of EGF receptor signaling. PMID- 1860885 TI - Kalinin: an epithelium-specific basement membrane adhesion molecule that is a component of anchoring filaments. AB - Basal keratinocytes attach to the underlying dermal stroma through an ultrastructurally unique and complex basement membrane zone. Electron-dense plaques along the basal surface plasma membrane, termed hemidesmosomes, appear to attach directly to the lamina densa of the basement membrane through fine strands, called anchoring filaments. The lamina densa is secured to the stroma through a complex of type VII collagen containing anchoring fibrils and anchoring plaques. We have identified what we believe is a novel antigen unique to this tissue region. The mAbs to this antigen localize to the anchoring filaments, just below the basal-dense plate of the hemidesmosomes. In cell culture, the antigen is deposited upon the culture substate by growing and migrating human keratinocytes. Addition of mAb to the cultures causes the cells to round and detach, but does not impair them metabolically. Skin fragments incubated with antibody extensively de-epithelialize. These findings strongly suggest that this antigen is intimately involved in attachment of keratinocytes to the basement membrane. This antigen was isolated from keratinocyte cultures by immunoaffinity chromatography. Two molecules are observed. The most intact species contains three nonidentical chains, 165, 155, and 140 kD linked by interchain disulfide bonds. The second and more abundant species contains the 165- and 140-kD chains, but the 155-kD chain has been proteolytically cleaved to 105 kD. Likewise, two rotary-shadowed images are observed. The larger of the two, presumably corresponding to the most intact form, appears as an asymmetric 107-nm-long rod, with a single globule at one end and two smaller globules at the other. The more abundant species, presumably the proteolytically cleaved form, lacks the distal small globule. We propose the name "kalinin" for this new molecule. PMID- 1860886 TI - Characterization of a new human osteosarcoma cell line OHS-4. AB - We present a new human osteosarcoma cell line designated OHS-4. These cells showed a high alkaline phosphatase activity that is not regulated by 1,25 dihydroxyvitamin D3. They exhibited a sensitive adenylate cyclase response to parathyroid hormone but not to prostaglandin E2 or human calcitonin. By Northern blot analysis we could detect type I collagen mRNA but none for type III collagen. The cells were able to produce human osteocalcin at a maximum level of 35 ng per million cells when exposed to 2.4 nM 1,25-dihydroxyvitamin D3 for 96 h. We purified this protein from conditioned media using successive chromatography and assessed its identity by partial amino acid sequencing. When injected into nude mice, the cells retained their osteogenic activity and developed calcified tumors. After Von Kossa staining, we observed nonmineralized osteoid deposits and mineralized deposits with a structure similar to that of trabecular bone by light microscopy. On the basis of its osteoblastic characteristics, this new osteosarcoma cell line may represent the human counterpart of the ROS 17/2 cell line. This cell line represents a valuable model for the isolation and characterization of human bone specific proteins. PMID- 1860888 TI - Macromolecular organization of chicken type X collagen in vitro. AB - The macromolecular structure of type X collagen in the matrices of primary cultures of chick hypertrophic chondrocytes was initially investigated using immunoelectron microscopy. Type X collagen was observed to assemble into a matlike structure with-in the matrix elaborated by hypertrophic chondrocytes. The process of self assembly was investigated at the molecular level using purified chick type X collagen and rotary-shadowing EM. It was shown that under neutral conditions at 34 degrees C, individual type X collagen molecules associate rapidly into multimeric clusters via their carboxy-terminal globular domains forming structures with a central nodule of carboxy-terminal domains and the triple helices radiating outwards. Prolonged incubation resulted in the formation of a regular hexagonal lattice by lateral association of the juxtaposed triple helical domains from adjacent multimeric clusters. This extended lattice may play an important role in modifying the cartilage matrix for subsequent events occurring in endochondral bone formation. PMID- 1860889 TI - Basic fibroblast growth factor is efficiently released from a cytolsolic storage site through plasma membrane disruptions of endothelial cells. AB - Cells of gut and skin frequently suffer mechanically-induced plasma membrane disruptions in vivo, and bioactive molecules, including basic fibroblast growth factor (bFGF), could enter and leave cytoplasm through these disruptions. We here provide three lines of evidence that bFGF is released with surprising efficiency through plasma membrane disruptions, resembling those known to occur in vivo, produced by scraping endothelial cells from their culturing substratum. First, 41% of the total of bFGF extractable in 1 M NaCl by freeze-thaw and sonication was released simply by scraping the endothelial cells. Second, relative to release of lactate dehydrogenase, cells wounded by scraping under conditions promoting greater than 60% cell survival released a significantly larger amount (up to twofold more) of growth promoting activity than did cells uniformly killed and irreversibly permeabilized by scraping in the cold or by freezing and thawing. Last, cells that survived membrane disruptions released, and contained, less bFGF on each subsequent wounding, consistent with release of bFGF through transient (i.e., survivable) membrane disruptions. A polyclonal antibody against bFGF completely neutralized the growth promoting activity released by scraping, confirming that bFGF is released through endothelial cell plasma membrane disruptions. Cell fractionation and immunolocalization, including a novel permeabilization technique for electron microscope immunolocalization, demonstrated a cytosolic location of bFGF. We conclude that many characteristics of bFGF--its broad spectrum of producing and target cell types, cytosolic location, efficient release through biologically and pathologically relevant plasma membrane wounds, and its release from cells that survive membrane wounds- make it a strong candidate as a "wound hormone" for rapidly initiating the cell growth required for routine maintenance of tissue integrity and/or repair after injury. PMID- 1860887 TI - Induced expression of syndecan in healing wounds. AB - We have studied the expression of an integral cell surface proteoglycan, syndecan, during the healing of cutaneous wounds, using immunohistochemical and in situ hybridization methods. In normal mouse skin, both syndecan antigen and mRNA were found to be expressed exclusively by epidermal and hair follicle cells. After incision and subsequent suturing, remarkably increased amounts of syndecan on the cell surfaces of migrating and proliferating epidermal cells and on hair follicle cells adjacent to wound margins were noted. This increased syndecan expression was shown to be a consequence of greater amounts of syndecan mRNA. Induction was observed already 1 d after wounding, was most significant at the time of intense cell proliferation, and was still observable 14 d after incision. The migrating cells of the leading edge of the epithelium also showed enhanced syndecan expression, although clearly less than that seen in the proliferating epithelium. The merging epithelial cells at the site of incision showed little or no syndecan expression; increased syndecan expression, however, was detected during later epithelial stratification. When wounds were left unsutured, in situ hybridization experiments also revealed scattered syndecan-positive signals in the granulation tissue near the migrating epidermal sheet. By immunohistochemical analysis, positive staining in granulation tissue was observed around vascular endothelial cells in a subpopulation of growing capillaries. Induction of syndecan in granulation tissue both at the protein and mRNA levels was temporally and spatially highly restricted. Granulation tissue, which formed in viscose cellulose sponge cylinders placed under the skin of rats, was also found to produce 3.4 and 2.6 kb mRNA species of syndecan similar to that observed in the normal murine mammary epithelial cell line, NMuMG. These results suggest that syndecan may have a unique and important role as a cell adhesion and a growth factor-binding molecule not only during embryogenesis but also during tissue regeneration in mature tissues. PMID- 1860890 TI - Aluminum fluoride stimulates inositol phosphate metabolism and inhibits expression of differentiation markers in mouse keratinocytes. AB - Mouse keratinocytes are induced to differentiate in vitro by elevating the level of extracellular calcium from 0.05 mM, where keratinocytes express a basal cell phenotype, to greater than 0.10 mM, where they express the differentiated phenotype. This process has been associated with a rapid, sustained increase in inositol phosphate (InsP) turnover, which precedes the expression of differentiation-specific proteins. In 0.05 mM Ca2+ medium, aluminum and fluoride salts (AIF4-), which combine to activate nonspecifically heterotrimeric guanine nucleotide-binding (G) proteins, cause a concentration-dependent increase in InsP metabolism in keratinocytes, and generate elevated intracellular diacylglycerol levels. This is associated with an inhibition of cell growth. Treatment with both AIF4- and Ca2+ greater than 0.10 mM resulted in an additive increase in InsP turnover, implying the presence of at least two responsive InsP pools. AIF4- inhibited the expression of differentiation markers induced by Ca2+ greater than 0.10 mM and altered the morphology of keratinocytes from squamous to dendritic, which was reversible upon withdrawal of AIF4-. Neoplastic keratinocytes, in which basal levels of InsP metabolism are higher than in normal cells, do not differentiate in response to Ca2+. Neoplastic keratinocytes responded to AIF-4 treatment with an even greater rise in InsP metabolism. AIF-4 also inhibited cell growth and reversibly altered morphology in neoplastic keratinocytes. These data suggest that InsP metabolism in keratinocytes is at least partially regulated by a G protein mechanism. Furthermore, an increase in InsP metabolism is not sufficient to stimulate differentiation and may be inhibitory to differentiation if exceeding limited increases. However, these observations cannot exclude the possibility that other AIF-4 stimulated pathways involving G or non-G proteins can also influence keratinocyte biology. PMID- 1860891 TI - Xyloside effects on in vitro hematopoiesis: functional and biochemical studies. AB - Xyloside supplementation of long-term bone marrow cultures (LTBMCs) has been reported to result in greatly enhanced proliferation of hematopoietic stem cells. This was presumed to be the result of xyloside-mediated perturbation of proteoglycan synthesis by marrow-derived stromal cells. To investigate this phenomenon, we first studied the effects of xyloside supplementation on proteoglycan synthesis by D2XRadII bone marrow stromal cells, which support hematopoietic stem cell proliferation in vitro. D2XRadII cells were precursor labelled with 35S-sulfate, and proteoglycans separated by ion exchange chromatography, isopyknic CsCl gradient centrifugation, and gel filtration HPLC. Xyloside-supplemented cultures showed an approximately fourfold increase in total 35S incorporation, mainly as free chondroitin-dermatan sulfate (CS/DS) glycosaminoglycan chains in the culture media. Both xyloside supplemented and nonsupplemented cultures synthesized DS1, DS2, and DS3 CS/DS proteoglycans as previously described. In contrast to previous reports, xyloside was found to inhibit hematopoietic cell growth in LTBMC. Inhibitory effects were observed both in cocultures of IL-3-dependent hematopoietic cell lines with supportive stromal cell lines and in primary murine LTBMCs. Xyloside was found to have a marked inhibitory effect on the growth of murine hematopoietic stem cells and IL-3 dependent hematopoietic cell lines in clonal assay systems and in suspension cultures. In contrast, dialyzed concentrated conditioned media from LTBMCs had no such inhibitory effects. These findings suggest that xyloside-mediated inhibition of hematopoietic cell growth in LTBMC resulted from a direct effect of xyloside on proteoglycan synthesis by hematopoietic cells. PMID- 1860892 TI - Characterization of sarcoplasmic reticulum in skinned heart muscle cultures. AB - The plasma membranes of rat heart muscle, grown in cell culture, were made permeable with saponin in a Ca-free solution. The cells were then supplied with a medium resembling the cytosol, and the adenosine triphosphate (ATP)-dependent Ca2+ sequestration was measured in the presence of oxalate. The nonmitochondrial component accounts for about 50% of the total Ca2+ uptake. The nonmitochondrial accumulation of Ca2+ within myocardial cells was found to be reversible by addition of the Ca2+ ionophore A23187. On the other hand, the Ca2+ antagonist D 600 (50 microM) had almost no effect on Ca2+ accumulation. Caffeine reduced Ca2+ accumulation in the skinned cardiomyocytes in a concentration-dependent manner. In addition, the anticalmodulin drug trifluoperazine (TFP) reduced Ca2+ accumulation in the skinned cells. Because of the analogy between nonmitochondrial ATP-dependent Ca2+ accumulation and the sarcoplasmic reticulum (SR) function with regard to the influence of various agents, it is assumed that we actually measure Ca2+ accumulation in the SR. The rate of Ca2+ accumulation into the SR measured during the development of the cardiomyocytes in culture shows an almost linear increase as a function of culture age. Amiodarone, a potent antiarrhythmic agent, and its metabolite, desethylamiodarone, inhibited Ca2+ accumulation into SR, which may explain their therapeutic effect. PMID- 1860894 TI - Bovine aortic endothelial cells release hydrogen peroxide. AB - Endothelial cells grown on microcarriers are able to release H2O2 to the extracellular environment without any added stimulus. The extracellularly released H2O2 can be detected by luminol-amplified chemiluminescence (CL) if horseradish peroxidase is added. The CL response can be reduced by catalase and blocked by superoxide dismutase, indicating that O2- could be a precursor for H2O2. The CL kinetics, i.e., a long lag time followed by a rapid shift to a new level, indicate activation of an O2(-)-producing enzyme. The cells are also able to protect themselves from H2O2 stimulation by both catalase and the glutatione system. Bradykinin stimulates the H2O2 release, but if the effect is directly stimulatory or if it acts by reduction of the protective system is at present unclear. The extracellularly released H2O2 could be a cause of injury to the endothelial cells or to the subendothelial matrix. PMID- 1860893 TI - Prolactin induces proliferation of vascular smooth muscle cells through a protein kinase C-dependent mechanism. AB - The effects of prolactin (PRL) on A10 (aortic smooth muscle) cell proliferation were examined by measuring both [3H]thymidine incorporation and increases in cell number. PRL induced a significant proliferative response from 10(-11) to 10(-7) M, with optimal activity at 10(-10) M. PRL also enhanced platelet-derived growth factor (PDGF)-induced proliferation. The possibility that PRL induces proliferation through a protein kinase C (PKC)-mediated mechanism was also examined. PRL caused activation of PKC from 10(-12) to 10(-8) M. Antiserum to PRL, a monoclonal antibody directed against the PRL receptor and the immunosuppressive agent cyclosporine A, were able to inhibit PRL-induced proliferation and activation of PKC. The PKC inhibitors, staurosporine, sphingosine, and 1-(-5-iso-quinoline-sulfonyl)-2-methylpiperazine (H-7) also antagonized both proliferation and PKC activation. These data strongly suggest that PRL-induced A10 cell proliferation is mediated through the PKC pathway and that this may play a role in vascular smooth muscle cell hyperplasia, characteristic of the pathogenesis of cardiovascular diseases such as hypertension and atherosclerosis. PMID- 1860895 TI - Coordination of protein-DNA interactions in the promoters of human H4, H3, and H1 histone genes during the cell cycle, tumorigenesis, and development. AB - Coordinate transcriptional control of replication-dependent human H4, H3, and H1 histone genes was studied by comparing levels of H3 and H1 histone promoter binding activities with those of H4 histone promoter factor HiNF-D during the cell cycle of both normal diploid and tumor-derived cells, as well as in fetal and adult mammalian tissues. Both H3 and H1 histone promoters interact with binding activities that, as with HiNF-D, are maximal during S-phase but at low levels in the G1-phase of normal diploid cells. However, these analogous DNA binding activities are constitutively maintained at high levels throughout the cell cycle in four different transformed and tumor-derived cells. Downregulation of the H3 and H1 histone promoter factors in conjunction with HiNF-D is observed in vivo at the onset of quiescence and differentiation during hepatic development. Hence, our results indicate a tight temporal coupling of three separate protein-DNA interactions in different histone promoters during the cell cycle, development, and tumorigenesis. This suggests that a key oscillatory, cell growth-control mechanism modulates three analogous histone gene promoter protein DNA interactions in concert. The derangement of this mechanism in four distinct tumor cells implies that concerted deregulation of these histone promoter factors is a common event resulting from heterogeneous aberrations in normal cell growth mechanisms during tumorigenesis. We postulate that this mechanism may be involved in the coordinate regulation of the human H4, H3, and H1 histone multigene families. PMID- 1860896 TI - Hydrocortisone in culture protects the blast cells in acute myeloblastic leukemia from the lethal effects of cytosine arabinoside. AB - The blast cells in acute myeloblastic leukemia (AML) respond to many of the same regulatory mechanisms that control normal hemopoiesis. These include the growth factors that bind to membrane receptors and steroid hormones or vitamins that have intracellular receptors. We report the effects in culture of the steroid glucocorticoid hydrocortisone on freshly explanted AML blasts from patients and on two continuous AML cell lines. Only small changes in clonogenic cell numbers in suspension cultures were seen in the presence of hydrocortisone. The most striking effect of the hormone was on the sensitivity of blasts cells to cytosine arabinoside (ara-C). In contrast to the response of AML blast cells to retinoic acid, a ligand for intracellular steroid receptors that sensitizes some blast populations to ara-C, hydrocortisone reduced the toxic effects of the drug. The protective action of hydrocortisone was not mediated through the cell cycle since exposure of blasts to hydrocortisone did not affect the percentage of cells in DNA synthesis as measured with the tritiated thymidine (3HTdR) "suicide" technique. The hydrocortisone effect could be demonstrated using a pulse (20 min) exposure protocol. Blasts pulsed with increasing specific activities of 3HTdR showed the usual response pattern with an initial loss in plating efficiency to about 50% of control, followed by a plateau, regardless of whether the cells had been exposed to hydrocortisone. Control blasts exposed to increasing ara-C concentrations gave very similar dose-response curves; in striking contrast, blast cells cultured in hydrocortisone, then pulsed with ara-C did not lose colony-forming ability even though the same population was sensitive to 3HTdR. The hydrocortisone effect was dose and time related; protection from ara-C increased from 10(-8) to 10(-5) M and was seen after 4 hr exposure but required 8 hr to reach a maximum. We conclude that hydrocortisone can protect blasts from the lethal effects of ara-C even while the cells are in active DNA synthesis. PMID- 1860897 TI - Analysis of the c-myc P2 promoter. AB - The cis-acting elements governing transcription from the murine c-myc P2 promoter have not been well defined. To gain a better understanding of the nature of the protein-DNA interactions that take place on the P2 promoter, protein binding assays were performed. The ME1a2 and E2F factors appear to be the predominant proteins bound to a region spanning positions -140 to -24 relative to the P2 transcription start site. By a number of criteria, these factors appear to be distinct. When c-myc promoter sequences were coupled to the chloramphenicol acetyltransferase gene (CAT) and transiently transfected into tissue culture cells it was found that optimal transcription from P2 was heavily dependent on the ME1a2 element. PMID- 1860898 TI - Interpreting nucleolar structure: where are the transcribing genes? PMID- 1860900 TI - Purification and physical properties of nematode mini-titins and their relation to twitchin. AB - We have isolated mini-titin from the nematodes Ascaris lumbricoides and Caenorhabditis elegans under native conditions using a modification in the procedure to prepare this protein from insect muscle. The proteins have an apparent molecular weight of 600,000 and appear in oriented specimens as flexible thin rods with a length around 240-250 nm. The circular dichroism spectrum of the Ascaris protein is dominated by beta-structure. The proteins react with antibodies to insect mini-titin and also with antibodies raised against peptides contained in the sequence predicted for twitchin, the product of the Caenorhabditis elegans unc-22 gene. Antibodies to insect mini-titin decorate the body musculature as well as the pharynx of wild-type C. elegans in immunofluorescence microscopy. In the twitchin mutant E66 only the pharynx is decorated. We conclude that the mini-titins of invertebrate muscles defined earlier by ultrastructural criteria are very likely to be twitchins, i.e. molecules necessary for normal muscle contraction. We discuss the molecular properties of the proteins in the light of the sequence established for twitchin. PMID- 1860899 TI - Analysis of the distribution of the INCENPs throughout mitosis reveals the existence of a pathway of structural changes in the chromosomes during metaphase and early events in cleavage furrow formation. AB - The INCENPs are two polypeptides of 135 x 10(3) and 150 x 10(3) Mr that enter mitosis as tightly bound chromosomal proteins, but subsequently leave the chromosomes altogether and become associated with the central spindle and cell cortex at the contractile ring. In the experiments reported here we have used confocal microscopy and immunoelectron microscopy to provide a detailed picture of the intracellular location of these proteins during mitosis. The experiments have not only revealed a number of new details concerning the properties of the INCENPs in mitosis, but have revealed a number of novel aspects of the mitotic process itself. The first of these is the existence of a sequential pathway of structural changes in the chromosomes that occurs during metaphase. This pathway is revealed by the existence of four distinct INCENP staining patterns in mitotic cells. In 'early' and 'early/mid' metaphase, the INCENPs gradually become concentrated at the centromeres, forming a ring at the center of the metaphase plate. During 'mid/late' metaphase they exit from the chromosomes, so that by late metaphase they are found solely in streaks that traverse the plate parallel to the spindle axis. The streaks probably correspond to INCENPs closely associated with microtubule bundles, perhaps as part of the stem body material. Examination of transverse optical sections of the spindle interzone during early anaphase reveals an unexpectedly high degree of order. The INCENP antigens are localized on fibers that are organized into a hollow ring 8 microns in diameter and approximately 4 microns beneath the cell cortex. Measurement of cellular dimensions in the confocal microscope reveals that the maximum diameter of early anaphase cells lies across the spindle equator, so that when the cleavage furrow forms, it does so around the maximum circumference of the cell. During anaphase, a subpopulation of the INCENP antigen becomes localized to the cortex where the furrow will subsequently form. This occurs prior to any other evidence of furrowing. Thus, binding of the INCENPs to this region may represent an early step in furrow formation. Together, these results suggest that the INCENPs may represent a new class of 'chromosomal passenger' proteins that are carried to the spindle equator by the chromosomes and subsequently perform a cytoskeletal role following their release from the chromosomes at the metaphase:anaphase transition. PMID- 1860901 TI - BWTG3 hepatoma cells can acquire phenylalanine hydroxylase, cystathionine synthase and CPS-I without genetic manipulation, but activation of the silent OTC gene requires cell fusion with hepatocytes. AB - The mouse hepatoma BWTG3 has been tested for its ability to grow in three different media that select for traits normally expressed in adult liver: homocysteine medium to select for cystathionine synthase (CS), tyrosine-free medium for phenylalanine hydroxylase (PH), and ornithine medium for carbamylphosphate synthetase-I (CPS-I) and ornithine transcarbamylase (OTC). In no case were the cells immediately capable of bulk growth, showing that all these traits were in some degree deficient. However, the cultures in homocysteine medium and in tyrosine-free medium both gave rise, spontaneously, to growing clones with frequencies of approximately 10(-3) and 10(-5), respectively. The deficiencies of CS and PH were accordingly excluded from further study, in view of their inherent instability. In contrast, no colonies ever formed in ornithine medium. Though neither CPS-I nor OTC were detectable in stock BWTG3 cells, it was found that CPS-I was readily inducible by hormones. The deficiency of OTC, however, appeared to be totally stable showing no reversion in response either to hormones or to azacytidine treatment. This deficiency was investigated by fusing the hepatoma to OTC+ liver cells prepared from normal or sparse-fur (spf) mice. Sparse-fur mice were used because their OTC is mutant and has a distinctive pH dependence. OTC+ hybrids were readily produced, without the need for any specific selection for OTC, and, in one case at least, with only minimal chromosome segregation. In all the OTC+ hybrids made with spf cells, there was clear reactivation of the wild-type, hepatoma-derived OTC gene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860902 TI - Overproduction and secretion of beta 2-microglobulin by a rat thymic epithelial cell line that expresses MHC class I heavy chain. AB - Major histocompatibility complex (MHC) class I antigens are constituted of dimers consisting of a peripheral light chain, beta 2-microglobulin (beta 2m) and a transmembrane heavy chain whose cell surface expression depends on its assembly with beta 2m. In contrast, soluble beta 2m can be secreted in the absence of heavy chain expression. The presence of beta 2m in medium conditioned by a rat thymic epithelial cell line, IT45-R1 (IT45) prompted us to investigate whether beta 2m could be secreted by cells that express MHC class I antigens. IT45 cells produce three to five times more beta 2m in the culture supernatant than another rat thymic epithelial cell line, IT26-R21 (IT26). The IT45 cell line exported beta 2m through a constitutive pathway of secretion, as indicated by the kinetics of production and localization of intracellular beta 2m. Although cells from the IT45 cell line expressed a much higher amount of beta 2m as compared to IT26 and NBT II cells (a rat bladder epithelial cell line), all three of these cell lines expressed the same amount of membrane and intracellular MHC class I heavy chain. These data are thus consistent with a constitutive secretion of beta 2m dependent upon an overexpression of MHC class I light chain as compared to the heavy chain. The amount of beta 2m mRNA and the ratio of beta 2m versus MHC class I heavy chain transcripts were higher in IT45 than in IT26 cells, indicating that overexpression of beta 2m in IT45 cells could be due to an enhanced level of beta 2m mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1860903 TI - The Golgi sorting domain of coronavirus E1 protein. AB - The coronavirus E1 membrane protein is confined to the Golgi after it is expressed in cells either by viral infection or via injection of synthetic RNA. We have investigated the features of the protein responsible for intracellular sorting and found that a C-terminal deletion of only 18 amino acids results in its transport to the plasma membrane. However, we have previously shown that this C-terminal region alone is not sufficient for Golgi retention. When E1 was fused to a cell-surface protein, Thy-1, the resulting molecule was retained in the Golgi. Various mutated forms of E1 whose destinations were the ER, cell surface or lysosomes were also fused to Thy-1, and in each case the fusion was sorted according to its E1 component alone. We argue that, in contrast to sorting signals for other membrane compartments, Golgi retention of E1 is not due to a single short peptide sequence. Instead, the Golgi 'signal' of E1 appears to require for its expression a domain comprising most of the sequence of the protein. PMID- 1860904 TI - Proteins of the mammalian mitotic spindle: phosphorylation/dephosphorylation of MAP-4 during mitosis. AB - The phosphoprotein composition of isolated CHO spindles was analyzed using the MPM-1 and MPM-2 antibodies, which are reactive with a phosphorylated epitope enriched in mitotic cells and present on the centrosome, kinetochores, midbody and fibers of the mitotic spindle. Several high molecular weight phosphorylated spindle proteins were detected on immunoblots, including species of 410 x 10(3) Mr, 350 x 10(3) Mr, a 230-240 X 10(3) Mr doublet, 210 x 10(3) Mr and 120 x 10(3) Mr. The temporal and spatial distribution of the MPM-reactive phosphoproteins was determined by examining spindle structures isolated from cells at various stages of mitosis. The susceptibility of the staining pattern to extraction with salt, a procedure known to remove most microtubule-associated proteins (MAPs), was also examined. The phosphorylated 210 x 10(3) Mr species was identified as MAP-4 and localized to the spindle fibers using (1) a polyclonal antibody raised against this species, that reacted with known MAPs, and (2) established MAP-4 antibodies that reacted with the spindle 210 x 10(3) Mr MPM-reactive proteins. The comparative immunoblot and immunofluorescence analysis establishes a cycle of phosphorylation/dephosphorylation of MAP-4 upon entry and exit from mitosis. Regarding the other MPM-reactive proteins, comparative immunofluorescence staining and immunoblot analysis of isolated spindle samples before and after salt extraction indicate that they may be constituents of the centrosome, kinetochores or midbody, but their definitive identification awaits the production of monospecific antibodies. PMID- 1860905 TI - Analytical studies on the chiral separation and simultaneous determination of pantothenic acid and hopantenic acid enantiomers in rat plasma by gas chromatography-mass fragmentography. AB - The chiral separation and simultaneous determination of D- and L-pantothenic acids and D- and L-hopantenic acids in rat plasma using gas chromatography-mass fragmentography are described. The method is based on deproteinization by ion exchange resin, extraction with ethyl acetate under acidic conditions, and derivatization to form several interesting compounds. After methyl esterification for carboxylic acid of D- and L-pantothenic acids, D- and L-hopantenic acids could be derivatized to trifluoroacetate, cyclic sulphite, and cyclic n butylboronate for hydroxy groups. D- and L-forms of these derivatives were completely separated by mass fragmentographic technique with quasi-molecular ions. Calcium salt of D-5-[(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl)amino]pentanoic acid was used as an internal standard for the determination of DL-pantothenic acids and DL-hopantenic acids. The detection limits of DL-pantothenic acids and DL-hopantenic acids in this method were 5 and 12 ng, respectively. This method could be applied to the study of plasma levels of D-, L-pantothenic acids and D-, L-hopantenic acids in rat. PMID- 1860906 TI - Gas chromatographic profiles of plasma total lipids as indicators of dietary history. Correlation with fat intake based on 24-h dietary recall. AB - Fasting plasma total lipid profiles were determined by high-temperature gas chromatography on a total of 1246 free living urban subjects, ages 20-59 years, from the Toronto-McMaster Lipid Research Clinic Population Study. Quantitative estimates of the major molecular species, lipid classes and lipid class ratios were correlated with a total of twelve dietary lipid components, including total saturated and unsaturated fats. oleic and linoleic acids, and cholesterol, to give appropriate Spearman coefficients (rS) and tests of significance (P) for groups of 775 males and 471 females. The intake of the various nutrients was derived from a 24-h dietary recall. The most significant correlations varying from rs +/- 0.1-0.4 and P less than 0.0001-0.0005 were between the intake of total fat, individual saturated and unsaturated fats, and the ratios of C50/C54 triacylglycerols and the C34/C36 phosphatidylcholines, which reflected the nature and quantity of the dietary fat consumed. Increases in dietary cholesterol and saturated fat produced small increases in plasma cholesterol and saturated triacylglycerols, while unsaturated dietary fat produced small decreases in saturated and increases in unsaturated plasma triacylglycerols. These changes in the plasma lipid parameters are consistent with those observed previously in much more limited dietary experiments with accurately known composition of ingested fats. It is, therefore, concluded that direct gas chromatographic profiling of plasma total lipids provides a simple and rapid method of verifying the overall correctness of the dietary recall. PMID- 1860907 TI - Separation of translationally active mRNAs by reversed-phase ion-pair high performance liquid chromatography. AB - An ion-pair high-performance liquid chromatographic method on C4 columns was developed for the separation of mRNAs. The addition of methylmercuric hydroxide markedly influenced the separation according to length of these molecules. A method is given to recover minute amounts of translatable mRNA from the organic phase. The resolution of mRNAs improved with increasing pore size of the column support. PMID- 1860908 TI - Concomitant determination of thiamin and its phosphate esters in human blood and serum by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method for the simultaneous determination of thiamin and thiamin phosphate esters in human blood or serum has been developed. The eluent consists of acetonitrile and phosphate buffer, in the ratios 90:10 (v/v) for the elution of thiamine and 60:40 (v/v) for the phosphate esters. The four compounds are eluted within 15 min. The detection limit is 13-16 fmol. Between-assay variation is 5-11%. Samples of whole blood and serum from 30 healthy adults were analysed. The following reference values were obtained for 15 females 15 males (nM, mean +/- S.D.). In serum: thiamin, 10.9 +/- 2.9/16.9 +/- 3.3; thiamin monophosphate, 8.3 +/- 1.5/3.7 +/- 1.5. In whole blood: thiamin, 29.6 +/- 10.0/33.4 +/- 10.4; thiamin monophosphate, 9.7 +/- 2.3/10.9 +/- 5.1; thiamin diphosphate, 121 +/- 29.6/165 +/- 40.4. PMID- 1860909 TI - Simultaneous determination of clebopride and a major metabolite N desbenzylclebopride in plasma by capillary gas chromatography-negative-ion chemical ionization mass spectrometry. AB - A procedure for the simultaneous assay of clebopride and its major metabolite N desbenzylclebopride in plasma has been developed. The method utilizes capillary gas chromatography-negative-ion chemical ionization mass spectrometry with selected-ion monitoring of characteristic ions. Employing 2-ethoxy analogues as internal standards, the benzamides were extracted from basified plasma using dichloromethane. Subsequent reaction with heptafluorobutyric anhydride produced volatile mono- and diheptafluorobutyryl derivatives of clebopride and N desbenzylclebopride, respectively. The methane negative-ion mass spectra of these derivatives exhibited intense high-mass ions ideal for specific quantitation of low levels in biological fluids. Using this procedure the recovery of the drug and metabolite from human plasma was found to be 84.4 +/- 1.5% (n = 3) and 77.4 +/- 4.7% (n = 3), respectively, at 0.5 ng/ml. Measurement of both compounds down to 0.10 ng/ml with a coefficient of variation of less than 10.5% is described. Plasma levels are reported in four volunteers up to 24 h following oral administration of 1 mg of clebopride malate salt. PMID- 1860910 TI - Determination of polysulphides in blood by gas chromatography and gas chromatography-mass spectrometry. AB - A sensitive and simple method to determine polysulphides in human blood, using an extractive alkylation technique and gas chromatography, has been devised. Polysulphides were alkylated with pentafluorobenzyl bromide, and then converted into bis(pentafluorobenzyl)disulphide by desulphuration with potassium cyanide. The disulphide was analysed qualitatively by mass fragmentography and quantitatively by gas chromatography with electron-capture detection. The lower limit of detection was 0.005 mumol/ml. Field testing in a suicide case confirmed the validity of the method. PMID- 1860911 TI - Automated analysis of oxolinic acid and flumequine in salmon whole blood and plasma using dialysis combined with trace enrichment as on-line sample preparation for high-performance liquid chromatography. AB - The use of dialysis as sample clean-up for high-performance liquid chromatography makes fully automated determination of drugs in whole blood and plasma possible. High recoveries of the analytes oxolinic acid and flumequine and the internal standard nalidixic acid are obtained after a short time of dialysis (7.3 min). The dilute dialysates are enriched on a small column packed with polystyrene. When dialysis is discontinued, the analytes are eluted by mobile phase to the analytical column. With UV detection the limit of detection was 50 ng/ml for both oxolinic acid and flumequine. Validation showed good precision and accuracy and good correlation between determinations in plasma and whole blood. PMID- 1860912 TI - Determination of mefloquine in blood, filter paper-absorbed blood and urine by 9 fluorenylmethyl chloroformate derivatization followed by liquid chromatography with fluorescence detection. AB - We describe a method for determination of mefloquine (MQ) in 100-microliters samples of urine, whole blood, and capillary blood collected on filter paper; quantification is by liquid chromatography with fluorescence detection at 475 nm of the 9-fluorenylmethyleneoxycarbonyl derivative. Whole blood and urine samples were prepared by extraction of MQ and internal standard from aqueous base with methyl tert.-butyl ether (MTBE), separation and evaporation of the MTBE layer, and derivatization using a solution of 9-fluorenylmethyl chloroformate in acetonitrile. Filter paper spots were immersed for 16 h in 0.1 M hydrochloric acid, followed by extraction with MTBE from aqueous sodium carbonate. The separated and evaporated organic layer was treated with the derivatizing solution. An aliquot was injected onto a high-performance liquid chromatography system using a C18 reversed-phase column and acetonitrile-water (72:28) mobile phase for filter paper spot extracts as for whole blood and urine extracts. The method has a limit of determination in blood, blood spots, and urine of 50 ng/ml with 100 microliters sample size (coefficient of variation = 16%). Linearity and precision (within-day and between-day) for the method are good. The MQ derivative was isolated and characterized spectroscopically. Values for MQ concentrations in filter paper blood spots compared favorably with values found in corresponding whole blood samples analyzed by a published method. PMID- 1860913 TI - Reversed-phase high-performance liquid chromatography of amphoteric beta-lactam antibiotics: effects of columns, ion-pairing reagents and mobile phase pH on their retention times. AB - The separation of five amino beta-lactam antibiotics by reversed-phase high performance liquid chromatography was studied as an insight into their retention behaviour. These five amphoteric compounds are cephradine, cephalexine, cefaclor, ampicillin and amoxicillin. Both octadecylsilane-bonded silica (C18) columns and phenyl-bonded silica (phenyl) columns were used, with mobile phase pH values between 2.5 and 7.4. In the absence of ion-pairing reagents the retention times for all the five compounds were the shortest at pH 4-6. The phenyl column was found to improve the separation between cephradine and ampicillin at pH values lower than 3, when these two compounds appeared as fused peaks on the C18 on C18 columns, with mobile phases both with and without ion-pairing reagents, were compared. The addition of 0.005 or 0.02 M tetraethylammonium acetate to the mobile phase did not result in significant ion-pair formation, except at pH values higher than 5.5. A strong ion-pairing effect was obtained at pH values higher than 6 with 0.005 or 0.02 M tetrabutylammonium phosphate, and the retention was decreased at pH values lower than 4. On the other hand, 0.005 M heptanesulphonic acid exhibited an ion-pair retention effect at pH values lower than 5. The molecular structures and pK(a) values were used to account for the retention behaviour of these antibiotics in the various mobile phases. PMID- 1860914 TI - High-performance liquid chromatographic determination of 4,4'-methylenedianiline in human urine. AB - A method is described for the determination of urinary 4,4'-methylenedianiline (MDA) by high-performance liquid chromatography (HPLC). MDA was extracted from hydrolyzed urine using C18 solid-phase extraction columns. The extract was analyzed by reversed-phase HPLC with electrochemical detection at a cell potential of 0.8 V. The method was very sensitive (detection limit 2.5 micrograms/l) and quantitation using 4,4'-ethylenedianiline as an internal standard correlated well with results by gas chromatography-mas spectrometry. Run to-run precision (n = 25) averaged 8.9%. In analysis of more than 160 potentially exposed workers, MDA was detected in less than 20% of the urines and concentrations ranged up to 210 micrograms MDA per g of creatinine. PMID- 1860915 TI - Simultaneous quantitation of loxapine, amoxapine and their 7- and 8-hydroxy metabolites in plasma by high-performance liquid chromatography. AB - Loxapine, its N-demethylated metabolite amoxapine, and their 7- and 8-hydroxy metabolites were determined simultaneously in plasma by a simple two-step extraction procedure followed by reversed-phase liquid chromatography. Baseline separation was achieved by a 5-microns Spherisorb C6 column. The mobile phase consisted of 5 mM phosphate buffer (with 14 mM orthophosphoric acid)-acetonitrile (with 105 microM nonylamine) (77:23, v/v). Assays of the steady-state plasma samples obtained from seventeen patients on loxapine showed substantial amounts of 8-hydroxy metabolites, lesser amounts of loxapine, amoxapine and 7 hydroxyloxapine and trace amounts of 7-hydroxyamoxapine. As 8-hydroxy metabolites possess only weak dopamine-D2 blocking activity, the final neuroleptic property of loxapine may be affected significantly by metabolic polymorphism. PMID- 1860916 TI - High-performance liquid chromatographic method for simultaneous determination of enantiomers of 5-dimethylsulphamoyl-6,7-dichloro-2-dihydrobenzofuran-2, carboxylic acid and its N-monodemethyl metabolite in monkey plasma and urine after chiral derivatization. AB - A quantitative method for the simultaneous high-performance liquid chromatographic (HPLC) resolution and determination of the enantiomers of 5 dimethylsulphamoyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxyl ic acid, a new diuretic, and its N-monodemethylated metabolite in monkey plasma and urine is described. The method includes diethyl ether extraction of the samples and S-(-) alpha-methylbenzylamide derivatization of the extract, followed by reversed-phase solid-phase extraction and injection of the resulting diastereoisomers onto a reversed-phase HPLC column. Baseline separation was obtained. The assay showed linearity over the range 0.1-50 micrograms/ml of plasma and 0.25-500 microliters of urine, with a lower limit of detection of ca. 0.01 micrograms/ml for each of the enantiomers. The method is adequate for pharmacokinetic and enantioselective disposition studies of both the diuretic and its metabolite. PMID- 1860917 TI - Method for the collection and analysis of volatile compounds in the breath. AB - A new method is described for the collection and assay of volatile compounds in the breath. Subjects expired into a pump-assisted collecting apparatus in which the breath was drawn through a water trap and then through an adsorptive trap where the volatile compounds were captured on graphitized carbon and molecular sieve. The sample was subsequently eluted from the trap by thermal desorption, concentrated by two-stage cryofocusing, then assayed by gas chromatography with flame ionization and flame photometric detection. Several compounds were regularly observed in the breath of normal human volunteers, including peaks eluting with the same retention times as isoprene, ethanol, acetone, acetaldehyde and carbon disulfide. As a quantitative assay for endogenous isoprene in the breath, the method was sensitive, linear, accurate and reproducible. This method provided a number of advantages: the collection technique was acceptable to volunteers and could be used at sites remote from the laboratory. The automated assay allowed isoprene and several other volatile compounds in the breath to be observed consistently and with improved sensitivity. PMID- 1860918 TI - Determination of 2-mercaptopropionylglycine and its metabolite, 2 mercaptopropionic acid, in plasma by ion-pair reversed-phase high-performance liquid chromatography with post-column derivatization. AB - A simple and fast high-performance liquid chromatographic method was developed for the simultaneous measurement of 2-mercaptopropionylglycine (Tiopronine) and its metabolite (2-mercaptopropionic acid) in human plasma after the administration of a pharmaceutical dosage form (Acadione). The sample treatment before high-performance liquid chromatographic analysis consisted of the reduction of the corresponding disulphides by tri-n-butylphosphine and protein precipitation with ethanol. Separation was achieved by ion-pair high-performance liquid chromatography on a reversed-phase column (LiChrospher RP 18e) with cetrimonium bromide as counter ion and detection by fluorimetry after post-column derivatization with a selective thiol reagent, i.e. pyrenemaleimide. The high frequency of the analyzed samples and validation results make the method suitable for pharmacokinetic studies, and this was demonstrated by the first results obtained after the administration of an oral dose of 500 mg of Tiopronine to two healthy subjects. PMID- 1860919 TI - Determination of the cytochrome P-450 IV marker, omega-hydroxylauric acid, by high-performance liquid chromatography and fluorimetric detection. AB - The formation of omega-hydroxylauric acid from lauric acid is an indicator of the activity of cytochrome P-450 IV family proteins. The two main metabolites of lauric acid, (omega-1)-and omega-hydroxylauric acid, have been completely separated by reversed-phase high-performance liquid chromatography. Measurement of lauric acid hydroxylase activity in microsomal liver samples, based on derivatization of the substrate and metabolites with the fluorescent agent 4 bromomethyl-6,7-dimethoxycoumarin, is a precise method (coefficient of variation = 7.6 and 10% for omega and (omega-1) metabolites, respectively) with good sensitivity (signal-to-noise ratio in microsomal samples of untreated rats greater than 20). In microsomal fractions from livers of rats treated with di-(2 ethylhexyl)phthalate the extent of omega-hydroxylation of lauric acid increased dose-dependently (ca. ten-fold). The (omega-1)-hydroxylase activity was not altered. A strong correlation between immunochemically determined cytochrome P 450 IVA1 and lauric acid omega-hydroxylase activity was found (r = 0.94, n = 30). PMID- 1860920 TI - High-performance liquid chromatographic determination of cortolic and cortolonic acids as pyrenyl ester derivatives. AB - A new procedure is described for the detection of the acidic metabolites of cortisol (cortoic acids) as the pyrenylmethyl-21-oic esters. The derivatizing reagent, diazomethylpyrene, was prepared by an improved procedure. The reagent was used at room temperature, required no catalyst, and was not restricted by stoichiometric requirements. The steroid esters were separated by reversed-phase high-performance liquid chromatography and analyzed simultaneously by their ultraviolet absorbance and fluorescence characteristics. Identities of the products were confirmed using the photodiode array detector to determine spectral profiles, absorbance maxima, and absorbance ratios. Further confirmation of identity of the cortoic acid esters used mass spectrometry under normal and collision-activated dissociation conditions. With the method described, a linear spectral response was obtained between 8 and 1680 fmol. Application of the technique to the analysis of steroid acids in human urine indicated the presence of cortoic acids. PMID- 1860921 TI - Simple thin-layer chromatographic purification procedure for the determination of cholesterol ester fatty acid compositions. AB - A mild procedure for the purification of methyl esters of the fatty acid components of cholesterol esters, from interfering free cholesterol and other contaminating residues, is described. Methyl esters and free cholesterol are formed during the methylation of cholesterol esters. When co-extracted, cholesterol and other contaminating residues interfere with the methyl esters because minute proportions of these residues tend to elute at the same retention times as palmitoleic and stearic acids, to yield unreliable but significantly higher values for palmitoleic (p less than 0.001) and stearic acids (p less than 0.0001), and correspondingly lower values for oleic acid (p less than 0.0001). Purification of methyl esters by thin-layer chromatography eliminates this problem and yields reliable analysis of cholesterol ester fatty acids, without measurable oxidation of unsaturated fatty acids. PMID- 1860923 TI - Determination of bencyclane in human plasma by means of capillary gas chromatography and nitrogen-phosphorus selective detection. AB - A sensitive and specific method for the determination of bencyclane in human plasma is presented. Bencyclane was extracted from human plasma with two 3-ml volumes of isooctane and was shaken for 10 min. The organic phase was separated and evaporated to dryness at 40 degrees C under a nitrogen stream. The residue was dissolved and an aliquot was injected into the gas chromatograph. The separation was performed with a DB-17 column with helium as the carrier gas. Nitrogen-selective detection was performed. The quantification was performed with the signal output. The limit of detection was 1 ng/ml. PMID- 1860922 TI - Determination of local anaesthetics in body fluids by gas chromatography with surface ionization detection. AB - Ten local anaesthetics were tested for their detection by gas chromatography (GC) surface ionization detection (SID). Lidocaine, mepivacaine and bupivacaine were detected with the highest sensitivity; their detection limit was 5-10 pg in an injected volume. The sensitivity of other drugs, such as procaine, dibucaine tetracaine and oxybuprocaine, was an order of magnitude lower than that of the above three local anaesthetics. A detailed procedure for isolation of local anaesthetics from human whole blood and cerebrospinal fluid (CSF) by the use of Sep-Pak C18 cartridges, before the GC-SID, is also presented. The recovery of lidocaine, mepivacaine and bupivacaine, which had been added to 1 ml of whole blood or CSF, was close to 100%. PMID- 1860924 TI - Determination of fendiline in human plasma by means of capillary gas chromatography and nitrogen-phosphorus selective detection. AB - A sensitive and specific method for the determination of fendiline in human plasma is presented. Fendiline was extracted from human plasma after the addition of phosphate buffer two times with 4 ml of n-hexane. The organic phase was separated and evaporated to dryness at 40 degrees C under a stream of nitrogen. The residue was dissolved and an aliquot was injected into the gas chromatograph. Chromatographic separation was performed with a DB-1 column with helium as carrier gas. Nitrogen-selective detection was performed. Quantification was performed with the signal output. The limit of detection was 1 ng/ml of plasma. PMID- 1860925 TI - High-performance liquid chromatographic assay for the determination of 5 aminosalicylic acid and acetyl-5-aminosalicylic acid concentrations in endoscopic intestinal biopsy in humans. AB - A high-performance liquid chromatographic method for the simultaneous determination of 5-amino-salicylic acid (5-ASA) and N-acetyl-5-ASA (Ac-5-ASA) concentrations in endoscopic mucosal biopsy homogenates is presented. The mean recoveries of 5-ASA and Ac-5-ASA from spiked blank biopsy homogenates ranged from 95.9 to 120% and from 92.5 to 100%, respectively. The coefficients of variation for 5-ASA and Ac-5-ASA were 0.7-8.6% and 1.4-12.9%, respectively. This method is useful for direct determination of topical availability of 5-ASA and Ac-5-ASA and probably an accurate parameter of drug bioavailability. PMID- 1860926 TI - Chromatographic analysis of methylmercaptopurine riboside in human plasma and urine. AB - An isocratic reversed-phase high-performance liquid chromatographic (HPLC) method for the determination of methylmercaptopurine riboside (MMPR) in human plasma and urine is reported. Plasma samples were prepared for analysis by addition of internal standard (6-dimethylaminopurine 9-riboside) followed by extraction using disposable C18 cartridges. Urine samples were filtered through a 0.22-micron membrane prior to HPLC separation. The column effluent was monitored at 289 nm and quantitation performed using peak heights. The linear range for MMPR determination was from 10 to 500 ng/ml in plasma and from 0.25 to 50 micrograms/ml in urine. The reported method is convenient, sensitive, and reproducible, illustrating its usefulness for application in pharmacokinetic studies. PMID- 1860927 TI - Selective liquid chromatographic assay for propylthiouracil in plasma. AB - A liquid chromatographic assay was developed to quantitate propylthiouracil in plasma using an internal standard, 5-propyl-2-thiouracil, of similar structure and physical properties. Caffeine, which coelutes with propylthiouracil, was removed by extraction from serum treated with base. No other compounds were found to interfere in the assay. The drug was extracted from plasma with chloroform with a recovery of 59.4% and the intra- and inter-assay coefficients of variation were 5.7 and 3.3%, respectively. The assay was linear to 3 micrograms/ml with a lower detection limit of 40 ng/ml for a sample volume of 1 ml. PMID- 1860928 TI - Determination of xanthenone-4-acetic acid in mouse plasma by high-performance liquid chromatography. AB - Xanthenone-4-acetic acid (XAA) was synthesised during a search for improved analogues of flavone-8-acetic acid, an antitumour agent with a unique mechanism of action but with a number of pharmacological disadvantages. We describe a simple, selective high-performance liquid chromatographic assay suitable for the detection of XAA in mouse plasma. After addition of an internal standard (3 methyl-XAA), plasma was acidified with trichloroacetic acid and extracted with toluene. After evaporation of solvent, samples were chromatographed on a C18 4 microns Novapak cartridge (mobile phase: water-acetonitrile-acetic acid, 65:35:2, v/v) using fluorescence detection. At the maximum tolerated dose of XAA (725 mumol/kg), nonlinear pharmacokinetics were observed. PMID- 1860929 TI - Determination of adriamycin in plasma and tissue biopsies. AB - A simple, rapid and sensitive method for the extraction and high-performance liquid chromatographic analysis of adriamycin in tissue and plasma is described. Tissue (5-100 mg) and plasma (1 ml) samples underwent a C18 Sep-Pak extraction into methanol. Chromatography was performed on a muBondapakphenyl column using a mobile phase of acetonitrile-0.1 M ammonium formate (pH 4.0) with a flow-rate of 2 ml/min. Fluorometric detection was used with an excitation of 480 nm and an emission of 550 nm. The procedure produced a linear curve for the concentration range 25-1000 ng/ml. The development of the assay produced rapid, repeatable and accurate results for both small tissue samples and plasma. PMID- 1860930 TI - Determination of diazepam and nordazepam in milk and plasma in the presence of oxazepam and temazepam. AB - For studies on the excretion of drugs into milk a sensitive high-performance liquid chromatographic assay was developed to quantitate diazepam and nordazepam in the milk and plasma of humans and rabbits in the presence of their major metabolites, oxazepam and temazepam. Flurazepam was used as an internal standard. The assay involves extractions with diethyl ether and an additional acid clean-up step. Chromatographic separation was achieved by a LiChrospher 60 RP-select B (5 microns) column and KH2PO4- acetonitrile (69:31, v/v) adjusted to pH 2.80 as a mobile phase. The same extraction and chromatographic conditions were suited to both types of samples, milk and plasma. The limits of determination using ultraviolet detection at 241 nm was for diazepam 20 ng/ml and for nordazepam 15 ng/ml. The absolute recoveries of diazepam, nordazepam and flurazepam in human milk were 84, 86 and 92% and in human plasma 97, 89 and 94%, respectively. The within- and between-day accuracy and precision for diazepam and nordazepam in milk and plasma at all concentrations tested (20-1500 ng/ml) were better than 8%. The high fat content which occurs in rabbit milk presented no limitation for the extraction of lipophilic diazepam: the method was successfully used to monitor milk and plasma concentrations of diazepam and nordazepam in lactating New Zealand White rabbits during 26-h infusions of diazepam (1.4 mg/h). PMID- 1860931 TI - Determination of diltiazem hydrochloride enantiomers in dog plasma using chiral stationary-phase liquid chromatography. AB - The separation and determination of d- and l-diltiazem hydrochloride in dog plasma by a two-column high-performance liquid chromatographic technique are described. Diltiazem hydrochloride and its metabolites were extracted from dog plasma and analyzed on a conventional column (Nucleosil 5C18) with a volatile buffer system. The column effluent of diltiazem hydrochloride was collected and evaporated. The enantiomeric ratio of the collected diltiazem was determined using a chiral column (Chiralcel OC). The method was accurate and sensitive. PMID- 1860932 TI - Analytical procedure for the determination of rufloxacin, a new pyridobenzothiazine, in human serum and urine by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method for the quantification of rufloxacin in human serum and urine has been developed and validated. The compounds, rufloxacin and internal standard, are extracted from buffered serum and urine using dichloromethane. They are then separated on an anion-exchange column using 0.05 M phosphate buffer-acetonitrile (80:20, v/v). The eluate is quantified by measuring the ultraviolet absorbance at 296 nm. The lower limit of detection for the analyte is 0.1 microgram/ml in serum and 0.05 micrograms/ml in urine. The method is linear from 0.3 to 10 micrograms/ml for serum and 0.1 to 10 micrograms/ml for urine. The method has been applied in a pharmacokinetic study in volunteers. PMID- 1860933 TI - Determination of the new anticancer agent KW 2149, 7-N-[2-[2-(gamma-L glutamylamino)ethyl)dithio)ethyl]mitomycin C, an analogue of mitomycin C. AB - The new mitomycin 7-N-[2-[2-(gamma-L-glutamylamino)ethyl)dithio)ethyl] mitomycin C (KW 2149) (I) proved to be active against a wide variety of experimental tumours. In order to perform pharmacokinetic studies with the new drug in Phase I sessions, a fast and reliable method has been developed based on the data of previous assays for mitomycin C. XAD-2 was preferred for isolation of I from blood plasma. The recovery of I was 50% whereas that of mitomycin C was 85%. Optimal separation was obtained on octadecyl silica columns with methanol-water (45:55, v/v) as mobile phase, while ultraviolet absorbance detection was performed at 375 nm. The assay enabled determination of I in a plasma concentration range of 20-1000 ng/ml using porfiromycin as internal standard. PMID- 1860934 TI - Simultaneous determination of beclomethasone, beclomethasone monopropionate and beclomethasone dipropionate in biological fluids using a particle beam interface for combining liquid chromatography with negative-ion chemical ionization mass spectrometry. AB - A new simple and sensitive assay has been developed for the simultaneous quantitative measurement of beclomethasone dipropionate and its hydrolysis products in human plasma and urine. Beclomethasone 17.21-dipropionate, beclomethasone 17-monopropionate, beclomethasone and the internal standard, dexamethasone 21-acetate, were measured by combined liquid chromatography and negative-ion chemical ionization mass spectrometry with methane as the reagent gas. A particle beam interface from Hewlett Packard was used. Under mild operating conditions, abundant and stable characteristic high-mass ions were generated in the ion source of the mass spectrometer by a resonance electron capture mechanism. The fast extraction procedure requires 1 ml of plasma or urine, and the quantification limit of the method is 1 ng ml-1 for the three tested compounds. PMID- 1860935 TI - Evaluation of a simple plasma catecholamine extraction procedure prior to high performance liquid chromatography and electrochemical detection. AB - The modified extraction method for catecholamines described in this study is reproducible, simple, rapid, economical and relatively hazard-free. This method is based on the principle that plasma catecholamines are selectively adsorbed on acid-washed alumina at pH 8.6 and then eluted at a pH between 1.0 and 2.0. No statistically significant differences were obtained by using either 0.5 or 1.0 ml of plasma with 0.5 or 1.0 ml of Tris buffer. A 15-min mixing time during the adsorption and desorption steps was found to be practical, but any standardized time up to 1 h can be used. If the washing step was omitted, the catecholamines could not be eluted from the acid-washed alumina. To prevent dilution, the alumina had to be centrifuged and not aspirated to dryness after the washing step. An amount of 50 mg of WA-4 alumina was found to be the most practical in this study. Extracted or unextracted plasma as well as catecholamine standards were stable for four months at -20 degrees C. PMID- 1860936 TI - Quantitation of tryptophan and other plasma amino acids by automated pre-column o phthaldialdehyde derivatization high-performance liquid chromatography: improved sample preparation. AB - Pre-column derivatization with o-phthaldialdehyde is a rapid and sensitive method for the quantitation of amino acids in biological fluids. This method uses acetonitrile as a deproteinizing reagent which gives improved recovery of tryptophan compared with 5-sulfosalicylic acid and permits the measurement of aspartic acid which coelutes with 5-sulfosalicylic acid. The method is automated to increase reproducibility and convenience. Mean coefficients of variation for peak areas relative to internal standard were 3.2 and 5.2% for amino acid standards and plasma samples, respectively. The presence of nitrilotriacetic acid stabilized the o-phthaldialdehyde reagent which is important in an automated system. The method is suitable for the analysis of large numbers of plasma samples where total tryptophan and aspartic acid are of interest. PMID- 1860937 TI - Diminished femoral antetorsion syndrome: a cause of pain and osteoarthritis. AB - The syndrome of diminished femoral antetorsion, evaluated in 111 joints of 59 children and adults, is described. Internal rotation of the femur was significantly decreased, and external rotation was increased. Femoral antetorsion was diminished in biplane radiographs to an 8.5 degrees mean value [1.0 degree in computed tomography (CT) scans]. Antetorsion values are higher in children, even in this syndrome. Pain was mainly experienced between the ages of 12 and 30 years. Ten patients had signs of beginning osteoarthritis. Rotational osteotomies performed to increase antetorsion were successful. PMID- 1860938 TI - Prevention of hip dislocation in cerebral palsy by early psoas and adductors tenotomies. AB - The effectiveness of psoas and adductor tenotomies for the prevention of hip dislocation was investigated in 40 hips of 24 total-body-involved children. Age at operation ranged from 1.6 to 10 years. Results were evaluated by the Reimers migration percentage (MP). Average follow-up was 3 years. An overall good result was observed in 67% of cases. Results were correlated with age and MP at operation. Successful results were obtained in 90% of patients under age 4 who had an MP less than 33%. Preventive surgery should be performed at 2 or 3 years of age, before the onset of hip dysplasia. PMID- 1860939 TI - Electrokinesiologic testing of walking in patients with spastic cerebral palsy. AB - Assessment of walking ability of patients with spastic cerebral palsy has long been a problem. In an attempt to obtain more precise and objective findings, we used the Polgon goniometry method. The study involved testing the gait of 36 spastic patients. We compared clinical findings and Polgon diagrams of healthy children and spastic patients pre- and postoperatively. The results were classified as very good to good, satisfactory, and poor. The advantages of Polgon are that it is painless, does not irritate the patient, and is a simple, objective method. Its disadvantages arise from a relatively large amount of artifacts and inadequacy when it is used on spastic patients. PMID- 1860940 TI - Equalization of lower limbs by epiphysiodesis: results of treatment. AB - Equalization of lower limb length was achieved by epiphysiodesis in 20 children. During the period under review the Phemister procedure was replaced by percutaneous epiphysiodesis, and orthoroentgenogram was superseded by computed tomography (CT) scanning. In five children with anisomelia, whose expected discrepancy was 4.5 cm, the results at maturity showed an average discrepancy of 0.7 cm. In 10 girls with limb-length discrepancy (LLD) caused by ischemic necrosis with congenital dislocation of the hip, the average LLD at maturity was 0.6, whereas the expected LLD was 4 cm. In five children with LLD caused by infection, the average discrepancy was 3.8 cm at the time of epiphysiodesis, whereas at maturity it was 0.5 cm. A good result was achieved in 90% of the patients. We recommend the Moseley straight-line graph, CT scanography, and percutaneous epiphysiodesis. PMID- 1860941 TI - Diaphyseal bone lengthening in children using Wagner device: long-term results. AB - In a series of 32 patients, the tibia was lengthened nine times and the femur 26 times. The lengthening was 4.1 cm in the tibia and 4.9 cm in the femur. The callotasis principle and atraumatic handling of the periosteum were considered important. The leg inequality was corrected appropriately, except in cases where the leg-length inequality was greater than 12 cm as a result of a progressive congenital deformity. Late femoral fractures occurred in six patients, but no tibial fractures were seen. One hip dislocation was seen after femoral lengthening, one talus deformation developed after the tibial lengthening, and one peroneal nerve entrapment was released operatively. One infection caused delayed bone union. Average follow-up time was 5.0 years. PMID- 1860942 TI - Contributing factors for osteogenesis in children's limb lengthening. AB - A progressive bone lengthening procedure according to the Wagner and Ilizarov technique and our own protocol was performed on 24 children (32 bones). Wagner's (transverse midshaft osteotomy, intraoperative lengthening of 1 cm and postoperative distraction of 1 mm/day) led to a marked reduction in osteogenic capacities. Patients operated on according to the Ilizarov technique had osteogenic reactions in the medullary cavity and on the posterior aspect of bone segments. Our own method, which included bone decortication, 5-7 days of neutral fixation without distraction, led to massive bone production in the medullary canal and around the bone segments. Rigid osseous bridging was present as early as 3 months after surgery. Neither the type of external fixator nor the location or shape of osteotomy had any specific influence on this massive bone reaction. Osteogenesis in limb lengthening is thus closely related to surgical management. PMID- 1860943 TI - Effect of scoliosis surgery on pulmonary function in patients with myelomeningocele. AB - Thirteen patients with myelomeningocele who required operation for scoliosis were tested for changes in pulmonary function 1 month before and an average of 13 months after spinal stabilization. The average age at the time of operation was 12 years 11 months. Ten patients had restrictive changes in pulmonary function preoperatively. Owing to the severity of scoliosis, an anterior approach to the spine including resection of ribs and division of the diaphragm was necessary for eight children. Postoperatively, despite these procedures, eight patients had an increase in vital capacity and six patients had an increased forced expiratory volume in 1 s. PMID- 1860944 TI - Allograft versus autograft bone in idiopathic scoliosis surgery: a multivariate statistical analysis. AB - The use of autograft versus allograft bone in scoliosis surgery is critically evaluated by a multivariate statistical analysis. Two groups of patients matched for age, angle of curve, and length of fusion, forming a consecutive series of posterior arthrodesis for idiopathic scoliosis, were evaluated. Group A consisted of 83 patients receiving autografts, and group B consisted of 99 patients receiving allografts. There was a significant reduction in operation time in the allograft group, and blood loss also decreased. After 1 year there was no significant difference in correction of the curve. Given the problems of discomfort at the donor site scar, we recommend the use of allograft bone in scoliosis surgery. PMID- 1860945 TI - Bone lesions in histiocytosis X. AB - Sixty-two patients with histiocytosis X were followed for an average of 5 years. The patients were classified into three groups: general visceral types (14 cases), multiple eosinophilic granulomas (nine cases), and solitary eosinophilic granulomas (39 cases). One hundred bony lesions were noted in 60 of the 62 patients. The bone lesions showed progressive improvement in single and multiple eosinophilic granulomas independent of treatment type. After biopsy, patients received no treatment unless there was a dangerous extension into the soft tissues because of its site, i.e., in the skull. In the general visceral types, chemotherapy was effective in visceral sites and in extensions of the tumor outside the bone but did not alter the natural history of the bony lesion. PMID- 1860946 TI - Critical review of infantile fibrous dysplasia: surgical treatment. AB - A critical review of the surgical treatment of 65 patients with infantile fibrous dysplasia demonstrated that "circumscribed" types of the disease generally do not require surgical treatment, while "extended" types, as well as Albright's syndrome, require early surgical treatment aimed at preventing development of skeletal deformities which are difficult to correct later. Prophylactic intramedullary nailing with nails of suitable caliber is most effective. PMID- 1860947 TI - Lower limb bone hemangiomas in children: report of two cases. AB - Hemangiomas of the bone are rare lesions, accounting for approximately 1% of all primary bone tumors. Hemangiomas occur fairly frequently in the vertebral bodies and the skull, but are unusual in other bones. We report two cases of unusual and fairly rare aspects of this vascular tumor in children. Both cases involved recurrences, which led to a wide bone resection in case 1 and to several curettages in case 2. In these two cases the histological type of hemangioma was capillary. In reviewing the literature we found no indication of wide resection of the benign forms in children. PMID- 1860948 TI - A new orthosis for the management of clubfoot and other foot and leg deformities in infancy and early childhood. AB - A new orthosis designed to deal with unilateral or bilateral idiopathic clubfoot after successful conservative or surgical treatment was used to maintain the correction and to prevent recurrence. Once the neutral position of the heel was achieved, the orthosis was found to be very useful in improving the correction of the hind-foot and/or the forefoot. The first 50 patients treated with the orthosis showed a 92% compliance rate for an average period of 9-12 months. PMID- 1860949 TI - Hip dysplasia, subluxation, and dislocation in cerebral palsy: an arthrographic analysis. AB - Fifty-nine hip arthrographic roentgenograms were performed on 31 children with cerebral palsy (CP) and plain radiographic evidence of hip deformity. Five levels of hip instability were defined by the arthrographic migration index (MI). The incidence of femoral head deformation increased with an increase in MI. A new measurement, defined by the intersection of Hilgenreiner's line with a tangent drawn from the lateral cartilaginous acetabular anlage, decreased proportionally with the increase in the MI. These findings indicate that progressive deformation of the cartilaginous acetabulum and femoral head occurs during (and, in some cases, before) evolution of hip instability in patients with CP. PMID- 1860950 TI - Rapid progression of hip subluxation in cerebral palsy after selective posterior rhizotomy. AB - Rapid progression of hip subluxation was noted in the year after selective dorsal rhizotomy in seven hips (six patients). The hips that subluxed progressed from a lateral extrusion index averaging 25% preoperatively as compared with 50% after rhizotomy. Although preexistent hip dysplasia was a predisposing factor, hips with an intermediate degree of preoperative lateral extrusion (12-25%) had variable results. Ongoing and more frequent evaluation of hip stability is necessary after dorsal rhizotomy. PMID- 1860951 TI - The acetabulum in congenital and neuromuscular hip instability. AB - Acetabular morphology in congenital and neuromuscular hip instability was evaluated with computed tomography (CT) and plain radiography. Thirty-three unstable hips in 27 children with congenital hip dysplasia, cerebral palsy, or spina bifida were studied. Fourteen normal hips in 14 children served as controls. Unstable hips in the children with congenital hip dysplasia demonstrated anterior and superior acetabular deficiency with increased acetabular anteversion. Global deficiency was present in acetabuli of cerebral palsy and spina bifida patients with anterior, posterior, and superior deficiencies. The acetabuli in cerebral palsy patients had significant posterior deficiency and were the shallowest of the groups evaluated. PMID- 1860952 TI - Late acetabular dysplasia following early successful Pavlik harness treatment of congenital dislocation of the hip. AB - We present the long-term results of Pavlik harness treatment in 61 patients with 74 affected hips. At the beginning of treatment, the hips were either dislocated and reducible or dislocated and irreducible. The average age of patients at follow-up was 12 years (range, 10-16 years). At 3- and 5-year follow-up, all of the hips appeared radiographically normal. However, at latest follow-up, 17% of the hips demonstrated changes in the acetabulum (an upward tilt of the outer portion of the acetabular roof or sclerosis in this area). This study emphasizes the importance of continued follow-up until patients treated for congenital dislocation of the hip reach skeletal maturity. PMID- 1860953 TI - Behavior of the proximal femur during the treatment of congenital dysplasia of the hip: a clinical long-term study. AB - The influence of the acetabular cover on the development of the proximal femur during the treatment of congenital dysplasia of the hip was studied in 47 children (58 hips) with a follow-up of 22 years. Varus osteotomy failed to correct hip dysplasia in 33 hips of 27 children. Chiari osteotomy was followed by a positive anti-Chiari effect (oval shaped acetabulum with proximal migration of the femoral head) in 15 children (20 hips). In five children (five hips) with coxa vara due to avascular necrosis, the anti-Chiari effect was negative. The combination of Chiari and varus osteotomy before the age of 8 years was followed by a positive anti-Chiari effect and recurrence of valgus deformity in seven of eight hips. The long-term failure of the varus and Chiari osteotomy, together with a review of clinical and experimental surveys, led us to prefer the acetabular redirectional osteotomy. PMID- 1860954 TI - Hamstring tenotomies in cerebral palsy: long-term retrospective analysis. AB - One hundred seventeen cerebral palsy patients were followed for a mean of 3.4 years after undergoing hamstring tenotomy by proximal semimembranosus release in conjunction with distal semitendinosus and biceps femoris release. Range of motion was significantly improved 1 year after the operation and remained so for 4 years. Thirty percent of nonambulatory patients improved at least one level in activity, some at up to 12 years of age. Minor recurvatum was observed at 1 year but became nearly nonexistent after 3-5 years. PMID- 1860955 TI - Effect of neonatal posture on later lower limb rotation and gait in premature infants. AB - The rotational profile of 265 children age 4-8 years who were born at the gestational age of less than or equal to 30 weeks and were nursed prone for several months after birth showed a marked outtoeing gait up to the age of 6 years. Their positive thigh-foot angles were significantly higher than those of the general population. These angles indicate that their outtoeing gaits were caused by marked external tibial rotation. PMID- 1860956 TI - Hypoplastic clavicles and lateral scapular redirection. AB - Three patients with bilateral hypoplastic clavicles and anterolateral displacement of the shoulders and scapulas on the thoracic cage are described. One patient had no family history of the disorder. The mother of the other patient had the same condition, suggesting an autosomal dominant inheritance pattern. In all three patients, the clavicle was underdeveloped and the scapula was redirected onto the lateral rather than the posterior thorax, bringing the entire shoulder forward. None of the patients have any significant functional restriction. PMID- 1860957 TI - Crankshaft phenomenon in congenital scoliosis: a preliminary report. AB - To determine whether or not the crankshaft phenomenon occurs after spinal fusion in patients with congenital scoliosis, we reviewed 23 curves in 21 patients who were operated on before age 10 years. Operative procedures consisted of various kinds of posterior fusions as well as anterior and posterior hemiepiphyseodeses. Seven of the 23 curves progressed greater than or equal to 10 degrees during the course of follow-up, and six of the seven demonstrated increased rotation and were believed to demonstrate the crankshaft phenomenon. No spines rotated without curve progression. The only statistically predictive factor was length of follow up. No curve that underwent anterior and posterior hemiepiphyseodeses demonstrated the crankshaft phenomenon. Although the crankshaft phenomenon can occur in young patients operatively treated for congenital scoliosis, apparently it can be prevented by anterior fusion. PMID- 1860958 TI - Persistent brachial plexus birth palsies. AB - Sixty-six brachial plexus palsies in 64 patients were retrospectively reviewed at the San Francisco Unit of the Shriners Hospital system in a 15-year period from 1973 to 1988. All patients were referred with persistent brachial plexus palsies caused by birth trauma. The distribution of palsies at birth included 34 upper palsies, three lower palsies, and 29 mixed (or global) palsies. At final follow up, the distribution of palsies had shifted and included 42 upper palsies, 6 lower palsies, and 14 mixed (or global) palsies. One patient had a persistent flail upper extremity. Many previously documented obstetrical risk factors were confirmed. Time to resolution or plateau averaged 4.5 months (range 3 weeks to 18 months). Only two palsies (one patient) resolved completely with time. PMID- 1860960 TI - Habitual hip dislocation. AB - A snapping hip is a common problem in children and young adults. The common etiologies of the syndrome have been well described. We believe that habitual dislocation may be a more frequent cause of the snapping hip syndrome than has been previously described. We report two cases of this rarely reported clinical entity presenting as a snapping hip. PMID- 1860959 TI - Ultrasonic features of the Osgood-Schlatter lesion. AB - Ultrasound was used to compare the knees of 10 boys and four girls with typical clinical Osgood-Schlatter lesions with 27 symptomless knees. The normal sonographic changes of the tibial tubercle with advancing age are described. In all children with Osgood-Schlatter lesions, the distal patellar tendon thickened and became more echogenic than normal tendons, and an anechoic zone of edema was seen anterior to the tibial tuberosity. Four knees disclosed a thin shell-like elevated fragment of the tibial tuberosity seen as an echogenic surface. In 12 knees, single or multiple fragments of the tibial tuberosity were easily shown. Ultrasound is proposed as a simple, fast, and reliable method for the diagnosis of the Osgood-Schlatter lesion. PMID- 1860961 TI - Tibia recurvatum as a complication of Osgood-Schlatter's disease: a report of two cases. AB - Premature fusion of the anterior part of the upper tibial epiphyseal plate is a rare complication of Osgood-Schlatter's disease. The resulting deformity is both unsightly and difficult to treat. We report two further cases and highlight the need for regular screening for this rare complication of a common disease. PMID- 1860962 TI - Focal fibrocartilaginous dysplasia: consideration of healing process. AB - We report two patients with unilateral tibia vara due to focal fibrocartilaginous dysplasia of the medial aspect of the proximal tibia. It appears that tibia vara, caused by a primary self-limited lesion at the proximal medial metaphysis, is corrected by the response of the proximal tibial physis. This finding would indicate that an infantile growth plate of the proximal tibia has a rather large potential to correct an angular deformity at the adjacent metaphysis. PMID- 1860963 TI - Electromagnetic metal localization for removal of retained hardware in children. AB - Retained hardware embedded deep in soft tissues or overgrown with bone poses a challenge to the surgeon assigned to its removal. A prototype of a hand-held electromagnetic metal detector-locater was used to localize retained hardware. Stainless-steel pins, screws, plates, and staples were located in 21 consecutive hardware removal procedures in 19 pediatric patients. Time to find the hardware, length of incision, blood loss, tissue maceration, and operative time were minimized. This preliminary study suggests that a metal locater may be a valuable tool when retained hardware is not palpable or readily apparent. PMID- 1860964 TI - The preventive medicine clerkship. PMID- 1860965 TI - Development of faculty consultants in a problem-based third year community medicine clerkship. AB - This paper describes the development of consultancy groups in behavioral science, epidemiology and biostatistics, and information science in a required community medicine rotation with a twenty year history. The addition of consultants to individual student tutors and field preceptors has led to a structure which promotes student-project flexibility, development of critical assessment skills and independent learning while maximizing faculty expertise and effectiveness. PMID- 1860966 TI - Problems in the control of schistosomiasis in Asir Province, Saudi Arabia. AB - Schistosomiasis, an endemic disease in the Kingdom of Saudi Arabia, is a major public health problem in Asir Province, the southwestern part of Saudi Arabia. The ongoing control program has concentrated on the elimination of the snail host by the use of chemical molluscicides, and on early detection and treatment of infected cases. Certain factors peculiar to this region make the application of the control strategy a difficult task. Thus, these methods of control over the years have not been very effective. Factors such as geography, climate, hydrographic conditions of this region, sources and spread of infection, and the role of primary health care centers are discussed in order to formulate plans for better control. Proper health planning is a dynamic process, and must constantly change based on past experience and epidemiological research. PMID- 1860967 TI - Health education in Nigerian secondary schools. AB - A survey of 600 secondary school teachers and 120 secondary school administrators was conducted in Oyo State, Nigeria, to identify their attitudes and practices regarding school health education. Nearly all teachers and administrators felt that health education is important and should be an integral part of the curriculum. Nonetheless, there were few resources and little curriculum time devoted to health education. Since many of the health problems of developing countries can be addressed by enhancing the health knowledge of the populace, health education in the schools of such countries deserves more emphasis. PMID- 1860968 TI - Body Mass Index and perceived weight status in young adults. AB - Body Mass Index (BMI) was calculated from self-reported height and weight for 1,123 university students who returned a questionnaire mailed to a 10 percent random sample of the entire undergraduate population of a large midwestern university. Seventeen percent of the females and 20 percent of the males were determined to be in excess of normal BMI standards. However, significantly more women (40%) considered themselves overweight in comparison to men (24%). Also, significantly more women (53%) than men (20%) reported experiencing discomfort due to excessive weight. Inaccurate perceptions of body image are common among individuals with eating disorders. There is a higher incidence of eating disorders among college-age women than among their male peers. A distorted body image as reflected by perceived overweight may serve as a marker for individuals at risk for eating disorders. PMID- 1860969 TI - Worksite health promotion in four Midwest cities. AB - A survey of worksite health promotion activities in nine areas of health was conducted in four Midwest cities--Winona and St. Cloud, MN; Eau Claire, WI and Sioux Falls, SD to determine how many worksites are involved in these activities; how many different kinds of programs they offer; and whether or not worksite involvement is growing in these areas of health. All worksites with over 100 employees were surveyed with a completion rate of 96% for eligible worksites. Comparing program offerings at worksites with such offerings by other community providers, we find worksites provide 40% of the total of such programs to adults. They tend to operate most programs independently of other community providers. Exercise and smoking cessation programs are most commonly offered. Worksites in the four communities significantly differed in the number of exercise program options offered and in the prevalence of worksite involvement in home, personal and drivers' safety programs. Compared to national survey results, worksites in these Midwest cities show a lower level of participation in heart disease and cancer screening activities. There is a high rate of dropout among current providers of heart disease screening activities and few nonproviders are initiating programs. Program initiation among nonproviders is highest in smoking cessation, weight loss and nutrition. Program growth among current providers is high in the areas of chemical dependency, exercise and personal, home and drivers' safety. PMID- 1860970 TI - Enhancement of immune response in Peyer's patch cells cultured with Bifidobacterium breve. AB - Bifidobacterium breve, included in fermented milk, was tested for adjuvanticity and mitogenicity using cells of mouse Peyer's patch, one of the gut-associated lymphoid tissues. Addition of B. breve enhanced antilipopolysaccharide antibody production in Peyer's patch cells and also anti-sheep red blood cell plaque forming cells in Peyer's patch cells cultured with sheep red blood cells. Furthermore, addition of B. breve accelerated proliferation of Peyer's patch cells, particularly B cells. In BALB/c mice, enhancement of proliferation by B. breve was also found in Peyer's patch cells from nude mice and a B cell-enriched fraction, including both the B cell fraction and plastic-adherent cells. Enhancement was not found in the fraction in which Sephadex G10-adherent and carbonyl-iron phagocytic cells were excluded from Peyer's patch cells or in a pure B cell fraction in which plastic-adherent cells were excluded from the B cell-enriched fraction of Peyer's patch cells. The proliferation of B cells was enhanced when the supernatant of plastic-adherent cells cultured with B. breve was added. It is concluded that B. breve activated plastic-adherent cells and that these cells secreted a soluble factor that enhanced proliferation of B cells. PMID- 1860971 TI - Deacylation of endotoxin during natural cases of bovine mastitis. AB - Acyloxyacyl hydrolase, a lysosomal enzyme that deacylates and thus detoxifies lipopolysaccharide (endotoxin) has been identified in bovine peripheral blood and milk neutrophils. Enzymatic activity increases on a per neutrophil basis during cases of experimental Escherichia coli mastitis. The objective of this study was to quantify acyloxyacyl hydrolase activity from milk neutrophils collected from mammary glands naturally infected with a variety of bacteria. Acyloxyacyl hydrolase activity was detectable in milk neutrophils isolated from cases of both Gram-negative and Gram-positive bacterial infections, with highest activities found in milk neutrophils from glands infected with organisms known to cause the most severe forms of mastitis. In addition, acyloxyacyl hydrolase activity was inhibited to varying degrees in mastitic milk by a nonprotein inhibitory substance. Nonenzymatic deacylation of endotoxin also occurred in mastitic milk, but to a lesser degree than enzymatic deacylation. Nonenzymatic deacylation of endotoxin was not found to occur in clinically normal milk. Severity of coliform mastitis in individual cows may be dependent in part on the interaction of endotoxin with milk neutrophil acyloxyacyl hydrolase activity, inhibition of acyloxyacyl hydrolase activity by an inhibitory substance, and the inherent ability of milk to deacylate endotoxin nonenzymatically. PMID- 1860972 TI - Effects of somatotropin on milk yield and physiological responses during summer farm and hot laboratory conditions. AB - The effects of bST on performance and physiological responses of lactating cows was studied under farm summer and laboratory heat conditions. Twelve cows, 90 to 50 d postpartum, were injected with either bST or vehicle solution for 30 d under farm summer and 10 d under either laboratory thermoneutral or heat conditions. Somatotropin increased milk yield by 6.1 (21%), 8.1 (32%), and 7.3 kg (35%) under the farm summer, laboratory thermoneutral, and heat conditions, respectively. Somatotropin also increased milk fat by 15 and 19% and dry matter intake by 16 and 18% under laboratory thermoneutral and heat conditions, respectively. Somatotropin increased the efficiency of feed conversion into milk without any significant changes in body weight and temperatures. Somatotropin reduced plasma concentrations of triiodothyronine and cortisol and had no effect on plasma prolactin and insulin concentrations. Somatotropin did not increase water intake; however, hematocrit was decreased. The results suggest that stimulatory effects of bST on milk production are still observed on heat-stressed cows without any significant indications of additional heat stress. PMID- 1860973 TI - Effect of somidobove sustained release administration on the lactation performance of dairy cows. AB - Lactation performance was determined on 190 multiparous Holsteins from five herds supplemented with 0, 320, 640, or 960 mg of somidobove every 28 d. The experiment consisted of 21 d of pretreatment and treatment periods of various lengths, depending upon stage of lactation of animals at first administration. Somidobove beginning in early (28 to 45 d in milk), mid (111 to 166 d in milk), or late (166 to 334 d in milk) stages of lactation consisted of 9, 6, or 3 administrations. Milk and 3.5% FCM yields were increased by each dose of somidobove in all stages. Milk composition and dry matter and energy intakes were similar among treatments within stage. Milk to DMI ratio and milk energy to net energy intake ratio were improved by somidobove. Gain was positive for all treatments, but less in somidobove-supplemented cows. Lower body weight and condition score at the completion of somidobove treatment resulted. For early cows, days to first estrus and days to first breeding were similar; however, total number of inseminations for cows receiving somidobove was twofold greater than control, resulting in a longer calving interval. Results demonstrated efficacy of somidobove administered every 28 d to lactating dairy cattle for increased milk yield. PMID- 1860974 TI - Effect of dry period length on milk production in subsequent lactation. AB - The effect of planned dry period lengths of 4, 7, and 10 wk on subsequent lactational yield was estimated with 366 cows in an experiment in which dry period was manipulated independently of milk yield prior to drying off. In two herds, all three treatments were compared within herd; in six herds, two treatments were compared within herd. Compared with a 7-wk planned dry period, a 3-wk decrease lowered the level of milk production by 2.8 kg of 4% FCM/d in the first 84 d of the subsequent lactation, whereas a 3-wk increase raised the level of milk production by .5 kg/d. In the first 168 d of the subsequent lactation, the difference between 4-wk and 7-wk planned dry periods was 2.7 kg/d, and the difference between 7- and 10-wk periods was .4 kg/d. There was no indication of interaction among planned dry period length and lactation number, days open in previous lactation, previous milk yield, breed, or health status with respect to effect on subsequent lactational yield. PMID- 1860975 TI - Sole ulcers in dairy cattle: associations with season, cow characteristics, disease, and production. AB - Epidemiological associations, expressed as odds ratios between variables obtained from dairy cow records and sole ulcer occurrence at claw trimmings were estimated with logistic regression analysis on data from 2204 and 1124 cows in lactation 1 and lactations 2 to 9, respectively. Sole ulcer in one foot or more than one foot occurred in 20.0 and 29.7% of cows in lactation 1 and in 23.5 and 24.7% of cows in lactations 2 to 9. The analysis revealed several complicated interactions. Trimming or calving in summer to fall was strongly associated with sole ulcer. Trimming later than 1 to 2 mo after calving was positively associated with sole ulcer depending on milk yield, body weight, or season of calving. If lactation 1 cows were treated for disease (limb, metabolic, digestive, or severe reproductive disorders), sole ulcer in more than one foot occurred earlier in lactation. Milk yield in early lactation and body weight were positively associated with sole ulcer. Heel erosion was associated with sole ulcer depending on season of trimming and parity. Presence of sole ulcer but not heel erosion in a lactation increased the risk of sole ulcer in the subsequent lactation. The interval between trimmings appeared to be important. PMID- 1860976 TI - Heel erosion and other interdigital disorders in dairy cows: associations with season, cow characteristics, disease, and production. AB - Epidemiologic associations between variables obtainable from dairy cow records and the occurrence of heel erosion, interdigital dermatitis, and interdigital hyperplasia at claw trimmings were estimated with multivariable logistic regression analysis on data from 1170 and 542 cows in lactation 1 and lactations 2 to 9, respectively. In the 17 herds, heel erosion, interdigital dermatitis, and hyperplasia occurred among 43.8, 4.5, and .9% of cows in lactation 1 and among 69.1, 7.6 and 5.9% of cows in lactations 2 to 9, respectively. Severity of heel erosion increased with parity, and risk increased with stage of lactation. Strong seasonal effects were present. Various combinations of veterinary treatments were associated with heel erosion and hyperplasia depending on parity, stage of lactation, and the presence of other claw disorders. In contrast, veterinary treatment had a protective effect for interdigital dermatitis in lactations 2 to 9. Severe degrees of sole ulcer increased the risk of heel erosion and interdigital dermatitis. The digital disorders were strongly associated in lactation 1 but not in later lactations. Heel erosion and hyperplasia were highly repeatable from one lactation to another. PMID- 1860977 TI - Effects of differences in starch content of diets with whole cottonseed or rice bran on milk casein. AB - Forty lactating Holstein cows in early to midlactation were used in a randomized complete block design to measure the effects of the following diets on milk casein. Treatments were four complete rations fed for ad libitum intake consisting of 1) 60% concentrate, 10% alfalfa hay, and 30% corn silage; 2) 45% concentrate, 10% alfalfa hay, 30% corn silage, and 15% whole cottonseed; 3) 60% concentrate, 5% alfalfa hay, 20% corn silage, and 15% whole cottonseed; and 4) 45% concentrate, 10% alfalfa hay, 30% corn silage, and 15% rice bran. Least squares means for daily DM intake all were significantly different and were 3.51, 3.90, 3.28, and 3.74% BW, respectively. Cows fed diet 3 had higher arterial glucose and insulin and venous insulin. Least squares means were significantly different for milk yield, 30.1, 31.4, 28.4, and 31.6 kg/d; for milk protein, 3.30, 3.13, 3.48, and 3.12%; and for casein N, .376, .358, 3.73, and .330, respectively. However, milk protein and casein N yields were similar for all cows. The diet that contained the highest percentage of starch did not result in a significantly higher percentage of casein N in the milk but had the lowest milk production. Both whole cottonseed and rice bran, substituted for concentrate, depressed milk protein percentage. PMID- 1860978 TI - Influence of source and amount of dietary fat on digestibility in lactating cows. AB - Digestibility of commercial fat supplements was determined in two experiments with high (59% of diet DM) forage diets. Experiment 1 was a preliminary trial in which six Jersey cows were in two 3 x 3 Latin squares to evaluate two formulations of calcium soap at two intake levels (500 and 1000 g/d). The two formulations were compared with control (0 supplement) within squares; the squares differed in amount of soap supplemented. Mean apparent digestibilities of fat were not influenced by source or amount of fat supplemented and averaged 82.5, 84.3, and 83.4% for control, 500, and 1000 g/d. In Experiment 2, six Jersey cows were in a 6 x 6 Latin square to compare effects of various commercial fats on digestibility of diet components at 2.85 and 5.7% (DM) added fat. Higher fat decreased digestibility of P and fatty acid. Fatty acid intake affected fatty acid digestibility quadratically, and variability among cows increased at higher fatty acid intake. Endogenous fecal fat was 55.9 g/d; apparent digestibility of fat was relatively constant at 80 to 82% between 2 and 5% of diet DM, whereas marginal true digestibility decreased linearly (4.4% units/100 g fatty acid consumed). There were no differences among fat sources in fatty acid digestibility. Rumen VFA were not influenced by dietary fat. PMID- 1860979 TI - Slow release somatotropin in dairy heifers and cows fed two levels of energy concentrate. 1. Performance and body condition. AB - Fifty-two Holstein dairy cows (27 primiparous) were used in a 2 x 2 factorial design during wk 9 to 39 of lactation to assess the effects of slow release recombinant bST (500 mg injected at 14-d intervals) and the effects of the level of energy concentrate in the diet on dairy performance. After a winter period, cows were turned out to pasture at wk 24 of lactation. During winter, cows given low concentrate (2.5 vs. 5.4 kg DM/d) ate significantly more corn silage (13.9 vs. 11.9 kg DM/d), so that treatment had no significant effect on any measured parameter. The milk yield of bST-supplemented cows increased by 2.1 kg/d (11.0%) throughout the total experimental period. The response did not differ according to parity. Milk fat content and SCC were not altered, but milk protein was lower (.8 g/kg) from cows receiving bST during winter, and lactose increased (.5 g/kg). Lactation curves of bST-supplemented cows showed a cyclic response in milk production. Gross efficiency of milk yield was improved (.18 units) by bST administration without change in diet digestibility. No difference due to bST was found in the health or reproduction of cows. Live weight change did not differ among the groups. Multiparous cows gained body condition (bST-supplemented animals gained less than controls: .1 vs. .7 point on a five-point scale; NS). Control primiparous cows gained body condition (.1 point) but bST-supplemented cows significantly lost body condition (1.4 point). PMID- 1860980 TI - Slow release somatotropin in dairy heifers and cows fed two levels of energy concentrate. 2. Plasma hormones and metabolites. AB - Fifty Holstein dairy cows (26 primiparous) were used to evaluate effects of level of concentrate and of slow release recombinant bST on plasma hormones and metabolites. Blood was sampled at wk 14 and 20 of lactation, which was 5 and 11 wk after the first bST injection. In addition, at d 3 and 10 after the third bST injection, diurnal profiles of somatotropin and metabolites were studied in 7 bST cows and 5 control cows by blood sampling every 20 min over 6 h. Supplementation by bST enhanced plasma somatotropin and insulin-like growth factor-I but did not significantly affect plasma concentrations of triiodothyronin and insulin. The bST supplementation increased plasma NEFA at wk 14 and reduced uremia at wk 20. Primiparous cows showed higher plasma NEFA and triiodothyronin than multiparous cows at both sampling periods, higher insulin-like growth factor I, and lower beta-hydroxybutyrate at wk 14, and higher glucose and lower insulin at wk 20. In the diurnal kinetic study, bST supplementation did not alter bST spike frequency and duration but increased spike magnitude, the area under the curve above the baseline, and the baseline mean. Sixty-one to 56% of the increase over controls in plasma bST total area was due to increase in the area under the curve above baseline. Preprandial NEFA were increased by bST at d 10. PMID- 1860982 TI - Heritability estimates of transformations of normally distributed records. AB - Milk yields were simulated for identical twin and parent-progeny pairs to determine effect of transformations on genetic variance. Use of identical twin pairs excludes variability due to Mendelian sampling and contribution by the other parent present in parent-progeny records. Phenotypic variances of 616,800; 1,439,200; and 2,261,600 and means from 2267 to 13,603 by increments of 2267 were used for linear scale records. Phenotypic variances of .01000, .01875, and .02750 and means equal to the natural logarithm of the means for linear scale were used for log scale records. Heritability varied from .05 to .95 by increments of .10. For each combination of parameters, 10 replicates of 10,000 pairs of relatives were created. Data normally distributed on a linear scale were log transformed. Log normally distributed data were exponentially transformed. Heritability estimates from correlations among relatives indicated heritability is larger for normally distributed data than for transformed data. For parent-progeny pairs, the difference increased as heritability increased, and for identical twin pairs, the differences were least at extremely large and small heritabilities. For both types of relative pairs, the difference increased as phenotypic variance increased. Absolute differences in heritability ranged from .0000 to .0089, a difference of little practical importance. PMID- 1860981 TI - Influence of calcium chloride on systemic acid-base status and calcium metabolism in dairy heifers. AB - Twenty heifers (12 Holsteins and 8 Jerseys) ranging from 15 to 22 mo of age (SD = 2.2 mo) and weighing 271 to 486 kg (SD = 72 kg) were offered diets containing 0, .5, 1, and 1.5% CaCl2 for 3 wk followed by a 1-wk readjustment period to evaluate the effect of CaCl2 on acid-base status, diuresis, and Ca metabolism. These evaluations were conducted under conditions simulating changes in dietary cation anion balance that potentially can be utilized as prophylaxis for parturient paresis during transition from dry cow period to lactation. Free proton concentration in blood increased and blood bicarbonate decreased with increasing dietary CaCl2. Plasma protein and blood hematocrit were unaffected by dietary CaCl2. Plasma Ca and urinary hydroxyproline excretion also were unaffected, but urinary Ca excretion rose with increasing dietary CaCl2, possibly reflecting either increased bone mobilization or intestinal absorption of Ca. Elevating dietary Cl increased both plasma Cl and urinary Cl excretion. During the readjustment period, all differences caused by CaCl2 disappeared. Based on the responses of acid-base status and Ca metabolism to the different dietary concentrations of CaCl2, we suggest that feeding 1% CaCl2 to dry cows for 3 wk prepartum could be a suitable method to prevent parturient paresis without causing detrimental acid-base disturbances. PMID- 1860983 TI - Animal model evaluations for Mexican Holsteins. AB - Genetic evaluations for milk yield of Holsteins in Mexico were computed from lactation and pedigree information from Holstein de Mexico. The US animal model system for national evaluations was adapted for Mexico. The primary change was in defining unknown-parent groups. Paths of unknown parents of bulls and sires of cows were combined and separate unknown-parent groups defined for parents of US, Canadian, and Mexican registration. Records with fewer than 305 d were expanded around management group mean; a lower limit of 50% of management group mean was imposed on these records. Based on 123,397 lactation records by 50,538 cows, evaluations were computed for 68,020 cows (including those without lactation records) and 4573 bulls. Estimate of breeding value improvement in 1986 from a quadratic curve was 87 kg milk. Animal model estimates of breeding value by birth year were similar to Modified Contemporary Comparison estimates. Correlations with previous evaluations were .90 for bulls and .85 for cows. Differences resulted from added data as well as changes in evaluation method. Cows born in 1985 with US sires had predicted breeding values for milk 380 kg higher than those with Canadian sires and 336 kg higher than those with Mexican sires. Equations were developed to convert milk PTA between Mexico and the US. No sire by country interaction was found; correlations of US and Mexican PTA were .90 (expected) and .91 (actual). PMID- 1860984 TI - Use of antibiotics in livestock and human health concerns. AB - Animal feed additives have for many years constituted the largest and most controversial category of antimicrobial use. The primary concerns addressed have been the generation of antibiotic resistance in animal bacterial and the influence of such resistance on human health. Studies designed to shed light on the controversy generally have yielded information leading to ambiguous conclusions. A 1989 report from the National Academy of Sciences was the latest of a long collection of assessments that have been meant to provide expert guidance to regulatory authorities on this matter. The FDA has been trying for some time to determine whether a regulatory decision on existing products is warranted. After several decades of research directed at this question, most qualified study groups have reported a paucity of appropriate information necessary to judge the reality of a public health risk. PMID- 1860985 TI - Multi-step reconstruction for solitary defects ... why? PMID- 1860986 TI - Hair transplantation in advanced male pattern alopecia. The role of incisional slit grafting. AB - The technique of incisional slit grafting is described and discussed. The results of the use of this technique for hair transplantation in patients with Norwood Type VII or advanced alopecia are reported. PMID- 1860987 TI - Prediction of subclinical tumor infiltration in basal cell carcinoma. AB - Two thousand-sixteen basal cell carcinomas (BCCs) were documented in terms of age, anatomic location, tumor diameter, initial excision depth, safety margin, histologic type, and the position of tumor outgrowths as determined by three dimensional histologic study of the tumor margins in paraffin sections (micrographic surgery). The extent of each subsequent excision was recorded until tumor-free tissue was reached. The results showed that BCCs have a highly irregular infiltration pattern and a predilection for small, fingerlike outgrowths whose bases occupy 1-30 degrees of the tumor circumference. When superficial extension was expressed mathematically, the resulting exponential functions varied highly significantly (P = .001) according to histologic tumor type and diameter. The resulting curves permitted very precise prediction of the probability of tumor-positive margins (ie, subtotal excision), depending on the safety margin, histologic tumor type, and tumor diameter. For example, the probability of tumor-positive margins after excision of a BCC up to 10 mm in diameter is 30% with a safety margin of 2 mm, 16% with a safety margin of 3 mm, and 5% with a safety margin of 5 mm. The probability of tumor-positive margins for fibrosing primary BCCs 10-20 mm in diameter is 48, 34, and 18% with safety margins of 2, 3, and 5 mm, respectively. Recurrent tumors have a significantly higher probability of positive margins (P = .001) than primary ones. Anatomic location and tumor age affect subclinical extension only indirectly. PMID- 1860988 TI - Partial-thickness wedge and advancement flap for upper lip repair. AB - Reconstruction of upper lip defects demands careful attention in order to reconstitute both normal function and normal appearance. These defects may involve mucosa, orbicularis oris muscle, skin, vermilion, or any combination of these structures. We will describe five cases in which there were defects created by Mohs micrographic surgery and present the concept of partial-thickness wedge in combination with a flap to repair these wounds. PMID- 1860989 TI - Practical phlebology. Sclerotherapy of large veins. AB - A practical, step-by-step guide for the sclerotherapy of large varicose veins is offered. First, an orientation regarding the place of sclerotherapy and surgery in the total treatment of varicose veins is given, with a practical clinical classification of varicose veins. This is followed by a detailed discussion of patient education before sclerotherapy, material to be used with recommended concentrations, injection technique, compression after sclerotherapy, instructions to the patient after injection, and procedures at subsequent visits. PMID- 1860990 TI - Long-term results of sclerotherapy and surgical treatment of the varicose short saphenous vein. PMID- 1860991 TI - Reconstruction of the lower lip and chin using local and random-pattern flaps. AB - Unlike the reconstruction of wounds found on more predictable and less variable anatomic subunits of the face, reconstruction of defects on the chin and lower lip often present special difficulties for the surgeon in accurately assessing and selecting the lines of incision that will provide the patient with the best cosmetic result. The author discusses the many factors which must be considered as part of that selection process and describes the uses of the most common local flaps for reconstructing wounds found in this anatomic location. PMID- 1860992 TI - Ethics in chemical peeling. PMID- 1860993 TI - Medical photography. PMID- 1860994 TI - Sclerotherapy: a debate on various issues. PMID- 1860995 TI - A review of otoacoustic emissions. AB - Otoacoustic emissions measured in the external ear canal describe responses that the cochlea generates in the form of acoustic energy. For the convenience of discussing their principal features, emitted responses can be classified into several categories according to the type of stimulation used to evoke them. On this basis, four distinct but interrelated classes can be distinguished including spontaneous, transiently evoked, stimulus-frequency, and distortion-product otoacoustic emissions. The present review details the findings that have been described for each emission type according to this classification schema. Additionally, the known features of emitted responses are discussed for both normally hearing and hearing-impaired humans and experimental animals, and with respect to their potential clinical applications. The findings reviewed here clearly indicate that future studies of otoacoustic emissions will significantly increase our understanding of the basic mechanisms of cochlear function while, at the same time, provide a new and important clinical tool. PMID- 1860996 TI - Acoustical tweezers. AB - A stable force potential well was generated by two collimated focused ultrasonic (3.5 MHz) beams propagating along opposite directions. Latex particles (270 microns diameter) and clusters of frog eggs were trapped in the potential well. The trapped object can be moved axially or laterally by moving one of the PZT focusing transducers that generate the ultrasonic focused beams. The axial position of the trapped object can also be maneuvered by tuning the frequency of the electrical voltage applied on the transducers. PMID- 1860997 TI - Ear canal cross-sectional pressure distributions: mathematical analysis and computation. AB - Cross-sectional pressure distributions, natural acoustic modes, and associated cutoff frequencies are determined for real ear-canal geometries using an asymptotic theory in combination with a numerical method. The technique is particularly well suited to obtain the higher modes, which are trapped near both ends of the ear canal. Results detail the influence of the canal geometry and frequency on the spatial distribution of the pressure. Adult ear-canal geometries are determined near the concha from ear-mold sections using a light microscope interfaced to a video-data-acquisition system. Computed results compare favorably to the exact solutions for circular and square acoustic waveguides. The cutoff frequency of the two adult ear canals studied averaged 20% less than the cutoff frequency of a circular tube of identical cross-sectional area. Inserting a probe microphone into the canal decreases the rate of decay of circumferential nonplanar modes while increasing the rate of decay of radial modes. Relative to the pressure beyond the tube, insertion increases the plane-wave component of the pressure around the tube by a multiplicative factor approximately equal to the square root of the original area divided by the occluded area. Eccentric placement of the probe tube has a relatively small influence on the cutoff frequency. The transition of the pressure distribution at the entrance to a simple plane wave in the core region of the canal is calculated and shown graphically for the actual geometry of two adult subjects. PMID- 1860998 TI - Are spontaneous otoacoustic emissions generated by self-sustained cochlear oscillators? AB - Theoretical analyses supporting the assumption that spontaneous otoacoustic emissions (SOAEs) can be described as self-sustained oscillations (requiring a power source) are reviewed and extended. Spectral and statistical properties of spontaneous otoacoustic emissions are examined and shown to be consistent with this assumption. Several alternative models of spontaneous emissions (noise driven saturating memoryless nonlinearity, noise-driven nonlinear-stiffness oscillator) are examined. Although some of these models are able to produce the types of statistical distributions of amplitude and displacement similar to those observed in the experimental data, this similarity is destroyed upon narrow-band filtering. PMID- 1860999 TI - New hearing threshold measurements for pure tones under free-field listening conditions. AB - Hearing thresholds for pure tones were measured under free-field listening conditions in the frequency range of 40 Hz-15 kHz. Results are consistent with the standard threshold specified in ISO 226 for frequencies up to 250 Hz, but a few dB below the ISO curve at higher frequencies. Thresholds are distributed normally on a logarithmic level scale with a standard deviation of approximately 5 dB. No significant differences between thresholds of male and female subjects were observed. PMID- 1861000 TI - Dissociation of pitch from timbre in auditory short-term memory. AB - In three experiments, untrained listeners made same/different judgments on pairs of pure or complex tones with periods that eventually differed by +/- 4%. On each trial, the two test tones were separated by 4.3 s, during which other tones (I) were heard but had to be ignored. The period (p) of the first test tone was randomly selected between 1/600 and 1/300 s. The period of each I tone was randomly selected among four possible values, close to p (+/- 3% or 6% apart) in some conditions, and remote from p in other conditions. In addition, from condition to condition, the spectral content of the I tones was varied independently of their periods: The I tones could have the same harmonic content as the test tones, or a very different harmonic content. Subjects' performances were much better when the periods of the I tones were remote from p than when they were close to p, as expected from previous findings by D. Deutsch [e.g., Science 175, 1020-1022 (1972)]. But, more importantly, the relation between the spectral contents of the I tones and the test tones had, by itself, practically no effect on performance. Thus performance was affected by the pitches of the I tones, but not by their timbres. These results suggest that pitch is processed independently of timbre in auditory short-term memory. PMID- 1861001 TI - Newborns' head orientation toward trains of brief sounds. AB - Four experiments assessed the importance of stimulus number, repetition rate, and duration for newborns' head orientation toward brief sounds and related those parameters to the critical ones found for adults. Infants' responses to various trains of repeated 14-ms rattle sounds were compared with those to a 10-s rattle sound, known to elicit head orientation. Directional responses did not differ from the standard when rattle bursts were repeated at a rate of 20 per second for 1 s (experiment 1). Responding did differ from the standard and deteriorated to chance levels when either the number of moderately paced (6/s) stimulus bursts was decreased to six or fewer (experiments 2 and 3) or the duration of rapidly repeated (24/s) bursts was shortened to 500 ms (experiments 4A and 4B). These results suggest that newborns' head orientation depends, in part, upon the number of stimulus bursts and stimulus duration. PMID- 1861002 TI - Differential sensitivity to vowel continua in Old World monkeys (Macaca) and humans. AB - Previous studies indicate that monkey pure tone frequency discrimination is quantitatively and qualitatively very different from that of humans: Monkey DLs at 1.0 and 2.0 kHz are up to 20 times larger than human DLs, and monkeys DLs increase as sensation level increases, in contrast to human DLs [Sinnott et al., J. Acoust. Soc. Am. 78, 1977-1985 (1985); Sinnott et al., J. Comp. Psychol. 101, 126-131 (1987)]. These results led to an hypothesis that monkey frequency discrimination is more dependent upon "rate" coding than is that of humans. The present study compared monkey and human DLs for formant frequency changes along three synthetic vowel continua /I-i/, /ae-epsilon/, and /a-v/. Here, monkey DLs for formants near 1.0 and 2.0 kHz (32-48 Hz) were only about two to three times larger than human DLs (11-21 Hz), and both monkeys and humans exhibited relatively similar, flat sensation level functions. Taken together, these data indicate that monkey and human frequency discrimination is more similar in the case of a complex vowel stimulus than in the case of a simple pure tone stimulus. Results are discussed in relation to "rate" versus "temporal" coding of tones and vowels in the auditory system. PMID- 1861003 TI - The emission pattern of vocalizations and directionality of the sonar system in the echolocating bat, Pteronotus parnelli. AB - The radiation patterns of the first three harmonics (approx. 30, 60, 90 kHz) of the mustached bat biosonar signal were measured from vocalizations elicited by cortical microstimulation. The primary foci of the acoustic beam patterns were in front of the mouth but somewhat below the horizontal plane. The prominent second and third harmonics showed sharp cutoffs between 20 degrees and 30 degrees lateral to the midline. Sidelobes were found, suggesting the influence of some vocal tract interference. When compared with previously measured estimates of the directionality of the auditory system, the vocal emission patterns are roughly complementary: Regions of maximum auditory sensitivity are found in areas of submaximal power for the sonar pulse beam pattern. The result is that, for the two most important harmonics, the "biosonar system" (i.e., vocal beam pattern plus receiver directionality) has a broader and more uniform directionality than either component alone. Therefore, within a limited region of space, echo amplitude will vary less as a function of angular displacement. This reduces the confounding influences of absolute sound pressure level on interaural intensity differences. PMID- 1861004 TI - Absorption of finite amplitude focused ultrasound. AB - Predictions of the absorption of focused finite amplitude waves based on weak shock theory have been tested experimentally. The characteristics of this absorption are qualitatively different from those associated with small signal losses. Under appropriate conditions, the absorption of finite amplitude ultrasound is determined largely by source amplitude, field geometry, and the nonlinear properties of the medium and is only weakly dependent upon the small signal absorption coefficient of the material. These effects are seen most dramatically in sharply focused sound fields. To emphasize nonlinear absorption in an experimental test of these predictions, measurements of heating were made in agar which has a very small linear absorption coefficient. Under appropriate conditions, nonlinear losses can make the effective absorption coefficient of this poorly absorbing material somewhat greater than the soft tissues of the body. PMID- 1861005 TI - Current status of Peterson-Barney vowel formant data. AB - A question concerning the status of the Peterson-Barney vowel formant data is raised. Two machine-readable copies of the data were located, compared, and found to contain minor discrepancies. These discrepancies were resolved by comparison with a listing of the original data. PMID- 1861006 TI - Tooth flexure. PMID- 1861007 TI - Is the solo practice doomed? PMID- 1861008 TI - Raising the root. A look at orthodontic extrusion. AB - A simple technique using bonded wires to establish anchorage and an attachment to a tooth requires a minimum of special materials or advanced skills in orthodontics. The bonded wire stabilizes the anchor unit and avoids any adverse tooth movement. PMID- 1861009 TI - New materials on the horizon. AB - Two areas of research will prosper and change operative dentistry in the future: developing light-cured glass ionomer technology further, and reinforcing direct composite resin technology. Successful development of restorative materials in these areas will have an immediate and long-term effect on the practice of operative dentistry in both affluent and poor countries of the world. PMID- 1861010 TI - Dentin bonding systems: a review of current products and techniques. AB - Many dentists are facing decisions regarding selection and use of dentin bonding systems. This article presents information on existing products and provides guidance on their use based on laboratory and clinical evidence. PMID- 1861011 TI - How finishing affects glass ionomers. Results of a five-year evaluation. AB - At least four cervical erosion/abrasion lesions were restored with glass ionomer materials in 30 patients. Some restorations were finished in 15 minutes, and some were finished 24 hours after placement. No significant differences were found after five years. PMID- 1861012 TI - Spotlight on lasers. A look at potential benefits. AB - Before lasers can be highly integrated into clinical practice, further research must prove the efficacy, efficiency, consistency and safety of this new technology. Currently, increased caries prevention and rapid laser etching are two potential benefits of laser technology. PMID- 1861013 TI - An approach to prosthodontics. Meeting the needs of our patients. PMID- 1861014 TI - Treatment of displaced articular fractures of the radius. AB - Forty patients with articular fractures of the distal radius in which anatomic reduction of the joint surface could not be obtained by closed manipulation or by ligamentotaxis with external fixators had a combination of percutaneous and/or open reduction techniques to restore articular congruity. X-ray films taken after treatment with an average follow-up of 4 years showed satisfactory extraarticular alignment in 85% of the cases, and 37 (92.5%) patients demonstrated an articular step-off of 1 mm or less at late follow-up examination. Radiographic evidence of radiocarpal arthritis was present in 5% of the cases at follow-up examination. PMID- 1861015 TI - External fixation of distal radial fractures: results and complications. AB - External fixation of unstable fractures of the distal radius yields satisfactory results but has a high complication rate. We studied thirty-five fractures in thirty-four patients to determine whether the results obtained with external fixation warranted it use. At a mean follow-up period of 31 months, the results of treatment were assessed by interviews and clinical and radiographic examination of both wrists. Twelve fractures had an excellent result, twelve had a good result, ten had a fair result, and one had a poor result. Radiographic results were graded excellent in ten fractures, good in thirteen, fair in five, and poor in seven. No correlation was found between the anatomical results and the clinical results or the patients' subjective ratings. Complications that were related directly to the fixation pins occurred in fourteen of the fractures. There were forty-five additional complications. The frequency of complications and the limitations of external fixation demand caution on the part of the surgeon to prevent iatrogenic morbidity, which would limit the benefits of the technique. PMID- 1861016 TI - Minor axial shortening of the radius affects outcome of Colles' fracture treatment. AB - Functional disability after a Colles' fracture was correlated to the degree of axial shortening of the radius measured at the site of distal radioulnar joint. According to the sum of demerit points, the functional end result was unsatisfactory (fair or poor) in 4% of the patients with an acceptable anatomic result, in 25% of the patients with grade 1 shortening (corresponding to a shortening of 3 to 5 mm), and in 31% of the patients with grade 2 shortening (shortening of more than 5 mm). The results suggest that even a minor axial shortening of the radius, without concomitant malalignment of the articular surface, carries an increased risk of permanent disability. PMID- 1861017 TI - Quantification of error in measurement of radial inclination angle and radial carpal distance. AB - Posteroanterior wrist radiographs of eight patients were evaluated by eight orthopedists. Radial inclination angle and radial-carpal distance were measured by use of a standardized technique. The standard deviation for radial inclination angle was 2 degrees. The standard deviation for radial-carpal distance was 1 mm. The measured rotational variation of radial inclination and radial-carpal distance is 1 degree and 1 mm, respectively, through a 10-degree arc of supination and pronation. PMID- 1861019 TI - Functional ranges of motion of the wrist joint. AB - We have examined 40 normal subjects (20 men and 20 women) to determine the ideal range of motion required to perform activities of daily living. The amount of wrist flexion and extension, as well as radial and ulnar deviation, was measured simultaneously by means of a biaxial wrist electrogoniometer. The entire battery of evaluated tasks could be achieved with 60 degrees of extension, 54 degrees of flexion, 40 degrees of ulnar deviation, and 17 degrees of radial deviation, which reflects the maximum wrist motion required for daily activities. The majority of the hand placement and range of motion tasks that were studied in this project could be accomplished with 70 percent of the maximal range of wrist motion. This converts to 40 degrees each of wrist flexion and extension, and 40 degrees of combined radial-ulnar deviation. This study provides normal standards for the functional range of motion of the wrist. PMID- 1861018 TI - Pressure distribution in the radiocarpal joint measured with a densitometer designed for pressure-sensitive film. AB - To measure the pressure distribution in the radiocarpal joint, a biomechanical study was done with fresh cadavers and pressure-sensitive film. With a load of 100 newtons, the contact locations were identified for 27 different wrist positions and the peak articular pressures and contact area were measured. Normal wrists were studied first, then modified to show different ulnar variances, and then to be models of malunited Colles' fractures of increasing severity. The contact locations of the scaphoid and the lunate were separate, and the mean peak articular pressures were 2.8 and 2.7 megapascals, respectively, for the normal wrists. In the radiolunate articulation, this mean increased by 27% with 2.5 mm ulnar minus variance and decreased by 22% with 2.5 mm ulnar plus variance. In the models of malunited Colles' fracture, the contact locations shifted from volar to dorsal, and the contact area decreased as the deformity became worse. PMID- 1861020 TI - Proximal row carpectomy: review of rheumatoid and nonrheumatoid wrists. AB - Proximal row carpectomy was first done in 1939 and was indicated for treatment of posttraumatic problems or Kienbock's disease. Use of this procedure in patients with rheumatoid arthritis has not been reported. Our series consists of eighteen wrists, nine with rheumatoid arthritis, and nine with other various nonrheumatoid conditions. Follow-up ranged from 12 to 120 months and included x-ray films and assessment of pain, range of motion, balance, grip strength, and patient satisfaction. Our results showed only two of the eight rheumatoid wrists to be satisfactory; failure was caused by pain and imbalance. Of the nonrheumatoid wrists, six of the eight were satisfactory, although in one of the six sclerosis is developing between the capitate and radius. Proximal row carpectomy is not recommended for the rheumatoid wrist but may be useful where other pathologic conditions are involved if the remaining articular surfaces are uninvolved. PMID- 1861021 TI - Proximal row fusion as a solution for radiocarpal arthritis. AB - A retrospective study evaluated the function of thirty-six patients treated by radius-scaphoid-lunate arthrodesis for painful posttraumatic radiocarpal arthritis from 1982 through 1987, and determined whether the procedure created arthritis or other functional problems in the remaining joints. Thirty-one men and five women with a mean age of 41 years were studied. The standard surgical technique employed iliac crest bone graft and internal fixation. Seven patients required revision of the proximal fusion to complete wrist fusion because of pain; arthritic changes in the midcarpal joint had been noted in these patients at the time of the limited fusion. The remaining twenty-nine patients required no further surgical treatment. Grip strength averaged 70% of the uninvolved side. The average arc of wrist flexion and extension was forty-eight degrees. Eighteen patients returned to their original employment, in many cases to heavy labor. Five did not return to work because of wrist problems. We conclude that the probability of a good functional result is high for this procedure if there is no midcarpal arthritis. PMID- 1861022 TI - Long-term results of Swanson interpositional wrist arthroplasty: Part II. AB - Fifty-eight Swanson silicone interpositional wrist arthroplasties were done in 47 patients between 1974 and 1984. Thirty-nine of these original wrists were available for follow-up an average of 5.8 years after operation. This is a continuation of our study previously published in this Journal. With increased follow-up, progressive deterioration of clinical results was noted. With a follow up of less than 2.5 years, 75% had relief of pain. After a follow-up of 4.8 years, 67% had relief of pain. Finally, with an average follow-up of 5.8 years, only 51% had relief of pain. Progressive radiographic changes are now obvious in each case compared with 70% of those cases reviewed at 4.8 years. Furthermore, we now have noted cystic changes in a significant proportion of the wrists radiographically. In several of these, silicone synovitis has been documented histologically. Our indications for this procedure have drastically narrowed. PMID- 1861023 TI - The Darrach procedure defended: technique redefined and long-term follow-up. AB - Thirty-three patients with pain and decreased range of motion after traumatic derangement of the distal radioulnar and ulna-carpal joint were treated with a modified Darrach distal ulnar resection. Their ages ranged from 22 to 75 years (average, 50 years). Twenty-seven patients had Colles' or other distal radius fractures. Seven patients had ulnar resection for treatment of distal ulnar carpal derangement. Follow-up averaged 54.4 months. The patients showed an average increase in extension of 58% and flexion increased by 40% (p less than 0.01). Pronation increased by 40% and supination increased by 60% (p less than 0.01). Average grip strength increased by 38% (p less than 0.05). Ninety-one percent good or excellent results were achieved with this procedure. The Darrach resection can predictably provide pain relief while improving strength and motion when attention is paid to minimal bony resection and meticulous soft tissue reconstruction. PMID- 1861024 TI - Long-term results of the minimal resection Darrach procedure. AB - Eighteen patients had a minimal resection Darrach procedure at the distal radial ulnar joint for treatment of posttraumatic arthritis. The follow-up averaged 8 years (range, 2 to 18 years). Fourteen patients were completely satisfied with the result achieved with the procedure and four were mostly satisfied. No patient had either subjective or objective evidence of distal ulnar instability. Grip strength for patients without radiocarpal arthritis was 84% of the uninvolved side. Preoperative ulnar variance was plus 4 mm and at follow-up minus 4 mm. At follow-up examination, four patients had ulnar carpal translocation. The average radial inclination angle of the patients with ulnar carpal translocation was 24 degrees, compared with 18 degrees for patients without ulnar carpal translocation. The minimal resection Darrach procedure gives excellent relief of pain without the instability attributed to the Darrach procedure. It must be used judiciously in patients who have a radial inclination angle above 23 degrees. PMID- 1861025 TI - Acute plastic deformation of the ulna in a skeletally mature individual. AB - Acute plastic deformation of a bone refers to traumatic bending or bowing without a detectable cortical defect. We present a case that is unusual in that bowing of the ulna occurred in a skeletally mature individual and was associated with injury to the distal radioulnar joint. In this patient, the symptoms were severe enough to warrant an ulnar osteotomy. The patient regained satisfactory function. Acute plastic deformity should be suspected whenever abnormal curvature of a long bone is noted, even in adults. If the distal radioulnar joint is dislocated, the deformation should be corrected as soon as possible to avoid permanent loss of forearm rotation. PMID- 1861026 TI - Radial shortening osteotomy for treatment of Kienbock's disease. AB - Sixteen patients who had radial shortening osteotomy for treatment of Kienbock's disease were reviewed. Ulnar minus variance averaged 3.3 mm. All patients had conservative management that failed. Six were stage II, six were stage III, and four were stage IV. Average follow-up was 4.5 years. In all patients osteotomies united within 3 months. Thirteen patients were totally relieved of pain, and three had mild pain. Motion in the dorsal palmar plane improved, on average, 15 degrees. Grip strength increased 20% to 30% after the operation. Follow-up radiographs did not show continued collapse of carpal height or disease progression except in one patient. No radiographic evidence of degenerative changes at the distal radioulnar joint materialized. As a safe, reliable, and consistently successful method of managing Kienbock's disease, we strongly recommend radial shortening. Excluding the rare extended stage IV disease in which midcarpal arthritis with or without intercarpal instability is present, we have successfully applied this technique to all stages of Kienbock's disease. We recognize that further collapse and progression of disease may occur in stage III and IV disease, as was evident in one patient 5 years after osteotomy. PMID- 1861027 TI - Concomitant scapholunate dissociation and Kienbock's disease. AB - Six men had concurrent scapholunate dissociation and Kienbock's disease, a finding suggestive of a common cause. Five patients attributed the onset of wrist pain to a single traumatic event. Three had x-ray evidence of scapholunate dissociation before the onset of lunate osteonecrosis. Biomechanical factors that may be of significance are ulnar minus variance, lesser compliance of the triangular fibrocartilage, ulnar translation of the carpus at impact with shear fracture through the lunate, and disruption of the scapholunate interosseous membrane occurring under similar stress. Lunate osteonecrosis may depend on a susceptible vascular pattern or intraosseous injury or both. The development of lunatomalacia complicates an already unstable wrist. Treatment options vary according to the clinical stages of each condition, although contrasting treatments have not established optimal care. PMID- 1861028 TI - A forty-three-year follow-up of a vitallium scaphoid arthroplasty. AB - Over the years various treatment options for scaphoid nonunions have been proposed. We present as a historical note the long-term follow-up of one such treatment, the insertion of a vitallium scaphoid. PMID- 1861029 TI - Prosthetic silicone scaphoid strains: effects of intercarpal fusions. AB - To assess stress shielding by partial intercarpal fusion, strains within a silicon scaphoid prosthesis were measured in five fresh upper extremities while the wrist was moved through a functional range of motion before and after capitate-lunate and capitate-hamate-lunate-triquetral intercarpal fusions. Capitate-lunate fusions resulted in an overall 18.4% reduction in compressive strains and a 10.8% reduction in tensile strains. Capitate-hamate-lunate triquetral fusions reduced compressive strains by 28.5% and tensile strains by 26.3%. Radially deviated positions and positions of extension produced no reduction in strains with the partial fusions. Modest strain shielding can be obtained with partial intercarpal fusions. The effect, however, is position dependent, and whether this degree of strain shielding can reduce the incidence of particulate synovitis remains unknown. PMID- 1861030 TI - A new vascularized bone graft for scaphoid nonunion. AB - Nonunion and avascular necrosis after scaphoid fractures continue to be problem sequelae because of unrecognized injuries, inadequate immobilization techniques, or insufficient treatment time. Screw fixation and inlay bone grafting techniques remain the options of choice, with successful union reported in approximately 90% of patients. However, prolonged immobilization with plaster up to 4 to 6 months is required with conventional techniques. With the use of standard latex injection techniques with vascular filling of vessels to less than 0.1 mm diameter in ten fresh cadaver dissections, we discovered a consistent vascularized bone graft source from the distal dorsoradial radius. We have used this vascularized bone graft source with good results in eleven patients with long-standing nonunion of the scaphoid. It is technically easy and seemingly offers the advantages of a decreased period of immobilization and a higher union rate. PMID- 1861031 TI - Magnetic resonance imaging to assess vascularity of scaphoid nonunions. AB - The unreliability of current methods of assessing of bone vascularity is well documented, precluding any prospective analysis of its influence on bone healing. In hopes of accurately predicting scaphoid vascularity, magnetic resonance imaging was used prospectively in patients with radiographic evidence of nonunion. Magnetic resonance imaging scans were compared to plain radiographs, tomograms, and the operative impressions of the surgeon. The diagnostic accuracy of each test was determined by a pathologist's interpretation of histological sections. Ten of thirteen surgical specimens were available for analysis. The magnetic resonance imaging scan accurately predicted scaphoid viability in all ten cases (three viable, seven avascular). This compared with diagnostic errors in six of ten plain radiographs, one of seven tomographs, and two of ten surgical assessments. Magnetic resonance imaging can accurately predict the vascularity of the ununited scaphoid. With further follow-up of these patients, the capability of the avascular scaphoid to heal will become evident. Definitive preoperative determination of the healing potential of scaphoid nonunions may then be possible, thereby aiding the surgeon's choice of the appropriate surgical procedure. PMID- 1861032 TI - Analysis of scaphoid fracture displacement by three-dimensional computed tomography. AB - Scaphoid fracture displacement was studied in twenty-five patients using three dimensional computed tomography. Fracture displacement was more readily detected and distinct in three-dimensional computed tomography images than in plain radiography. Two different types of offset of the distal fragment with respect to the proximal fragment are described on three dimensional computed tomography; volar type and dorsal type. In the volar type, the distal fragment overhung in the volar direction relative to the proximal fragment and was frequently accompanied by humpback deformity and axial rotation. In the dorsal type, the distal fragment slipped dorsal on the proximal fragment and was commonly accompanied by humpback deformity. The volar type had a transverse or vertical fracture line on both the volar and dorsal surfaces of the scaphoid, while the dorsal type had a horizontal fracture line. The volar type was frequently found when the fracture was distal, whereas the dorsal type was noted more frequently for proximally located fracture. PMID- 1861033 TI - Nonunion of a pathologic juvenile scaphoid fracture after osteomyelitis. AB - A patient with osteomyelitis of the scaphoid in childhood resulting in a pathologic fracture with nonunion is presented. This ununited fracture of the scaphoid was successfully grafted eight years later with a satisfactory outcome. PMID- 1861035 TI - Scapho-lunate distance and cortical ring sign. AB - The scapho-lunate distance was measured on posteroanterior radiographs of 100 normal wrists. The scapho-lunate distance measured a mean of 3.7 mm +/- SD 0.6 (range from 2.5 to 5.0 mm). The mean for 44 male wrists was 4.0 mm, and for 56 female wrists it was 3.6 mm. These results indicate that a scapho-lunate distance of up to 5 mm is not necessarily indicative of carpal instability. None of these normal wrists had a scaphoid "cortical ring" sign. PMID- 1861034 TI - Simulated scaphoid proximal pole fracture. AB - Five fresh cadaver upper extremities were studied with use of a static positioning frame, pressure-sensitive film, a microcomputer-based videodigitizing system, and a Sun station image analysis system to assess the load bearing characteristics of the scaphoid in the proximal carpal joint. Specimens were studied in their normal condition, after a proximal pole osteotomy of the scaphoid, and after resection of the proximal pole of the scaphoid. The amount of contact area born through the scaphoid fossa was essentially the same whether the scaphoid was intact, or after a simulated scaphoid fracture of its proximal pole, or after resection of the proximal pole. The scaphoid contact area and pressure, although overall relatively constant, was redistributed after osteotomy, resulting in increased contact area under the distal fragment and no change or a slight decrease in the contact area under the proximal fragment of the scaphoid. After resection of the proximal fragment, all scaphoid contact area and pressure was born by the distal scaphoid fragment. The contact area and pressure characteristics of the lunate remained unchanged in all conditions compared with the normal condition. There were no significant changes in the locations of the centroids of the scaphoid segments and the lunate in any of the conditions tested. PMID- 1861036 TI - Abductor pollicis longus tendon arthroplasty of the trapezio-metacarpal joint: surgical technique and results. AB - Tendon interposition resection arthroplasty of the trapezium is a valuable tool in treating osteoarthrosis of the first carpometacarpal joint. A previously unreported modification of such an operation is described in which a part of the abductor pollicis longus tendon is used as an interposition material. This technique was employed in a series of thirty-nine thumbs. After a minimal follow up period of 2 years, the results of the operation are graded excellent in 48% of the patients, good in 35%, and average in the rest. Grip strength, as well as pinch strength, is about three quarters of the normal average. No patient needed a further operation. PMID- 1861037 TI - Tendon arthroplasty of the fifth carpometacarpal joint for treatment of posttraumatic arthritis. AB - Resectional arthroplasty with interposition of a rolled tendon spacer was used to treat posttraumatic arthritis of the fifth metacarpal-hamate joint in eight patients. The average follow-up was 5 years. All of the patients subjectively rated the functional capability and the cosmetic appearance of their hands as good or excellent. After operation, there was a net increase of 30% in the average grip strength of the study group. The motion preserved at the small finger carpometacarpal joint facilitated power function of the hand. PMID- 1861038 TI - The fourth carpometacarpal joint. AB - The base of the fourth metacarpal and the corresponding hamate/capitate articulation were the areas of most significant variation in 142 cadaveric wrists that were dissected to assess the variation of the shapes of the second through the fifth carpometacarpal joints. Five different shapes of the fourth metacarpal base were identified. The base of the fourth metacarpal was generally either flat (85.9%) or conical (14.1%). There was a fourth metacarpal/capitate articulation present in 81.7% of the specimens. The presence or absence of a fourth metacarpal/capitate articulation and whether or not the fourth metacarpal base was flat or conical were easily identifiable on radiographs. Specific types of fourth metacarpal bases could not, however, be identified by radiography. PMID- 1861039 TI - Positional dislocation of the pisiform. AB - Positional dislocation of the pisiform repeatedly occurred in the right wrist of a 19-year-old man following a motorcycle accident. The pisiform repeatedly dislocated distal to the triquetrum when the wrist was extended to 45 degrees or more, and the pisiform was reduced to proper joint congruity after wrist flexion of 55 degrees or more. The patient had a background of generalized joint laxity. Resection of the pisiform resulted in a pain-free, fully functional wrist. PMID- 1861040 TI - Palmar lunate transtriquetral fracture dislocation. AB - A palmar lunate transtriquetral fracture dislocation with a concomitant radial styloid avulsion fracture has not been described before in the literature. This injury represents an interesting variation of stage IV perilunar instability. Treatment was complicated by persistent scapholunate dissociation (rotary subluxation of the scaphoid) after attempted closed reduction and percutaneous pinning. At open reduction, the proximal half of the triquetrum, which had been dislocated palmarward with the lunate and which had been thought to be reduced after our attempted closed reduction was indeed returned to its normal position. However, it was rotated 180 degrees on its transverse axis. Restoration of the normal scapholunate interval was not possible until the triquetral fracture was reduced. PMID- 1861041 TI - Avascular necrosis and vascular anatomy of the metacarpals. AB - Aseptic necrosis of the metacarpal head is extremely rare and has been described in association with systemic lupus erythematosus, steroid use, trauma, and other sites of bone infarction. The long metacarpal is the most commonly involved. The extrinsic and intrinsic vascular anatomy of the metacarpal is described in fifty metacarpal specimens. No definite conclusions can be drawn about anatomic variations in blood supply between the different metacarpals. However, in 35% of the specimens, a main arteriole in the distal epiphysis was absent, making these metacarpal heads solely dependent on small circumferential pericapsular arterioles. This group of metacarpals, when associated with other risk factors, such as trauma, systemic lupus erythematosus, or steroid use, may be at increased risk for the development of aseptic necrosis. PMID- 1861042 TI - External fixation of metacarpal and phalangeal fractures. AB - External fixation is rarely employed in the treatment of hand fractures, and few reports describing this technique have been published. This is a report on 26 patients with 30 hand fractures (19 metacarpal and 11 phalangeal) treated by closed reduction and external fixation. The fixation consisted of percutaneous and transversely applied Kirschner wires that were fixed externally with methylmethacrylate rods. Active range of motion exercises were started 1 week after reduction with the external fixator in place. Percentage return of total range of motion in phalangeal fractures varied from 66% to 98% (mean, 84%), and in metacarpal fractures it varied from 77% to 100% (mean, 96%). PMID- 1861043 TI - Rotational step-cut osteotomy for treatment of metacarpal and phalangeal malunion. AB - Metacarpal and phalangeal malunion after fracture or replantation frequently causes rotational deformities with scissoring during digital flexion. Transverse osteotomy at the metacarpal base has been advocated for derotation, but this only partially corrects scissoring resulting from phalangeal malunion. We describe the results of rotational step-cut osteotomies at the site of malunion. There were twenty-three osteotomies in eighteen patients; seven metacarpal and sixteen in the proximal phalanx. The value of the technique is supported by the results; speedy healing of bone, satisfactory alleviation of deformity, and a useful gain in range of motion in many patients. PMID- 1861044 TI - Comminuted fractures of the basilar joint of the thumb: combined treatment by external fixation, limited internal fixation, and bone grafting. AB - Displaced, comminuted fractures of the thumb carpometacarpal joint were treated by intermetacarpal external fixation, anatomic reduction of the joint surfaces, bone grafting and adjunctive internal fixation in thirteen patients. Retrospectively, at an average follow-up time of 35 months, nine patients showed a good result and one patient had a fair result. All fractures had united without secondary displacement, but focal irregularities of the joint surface were commonly seen. As compared with the uninvolved side, axial rotation averaged 79%, radial abduction 89%, key pinch 88%, and grip strength 81%. PMID- 1861045 TI - External fixator pin insertion techniques: biomechanical analysis and clinical relevance. AB - A series of identically matched pairs of fresh-frozen canine femora (approximating human radii in size and dimension) were used to mechanically compare pull-out strength between 4 mm predrilled, self-tapping, half-pins and 4 mm self-drilling, self-tapping half-pins with drill bit-like cutting flutes. A second biomechanical and videotape analysis was done comparing the differences of pin insertion by power versus hand drilling. Results indicated a mean 22% reduction in bone purchase of self-drilling, self-tapping pins compared with that of predrilled pins and a marked increase in depth of insertion required of the self-drilling pins for comparable pin purchase (10 mm). It was also observed that a visible "wobble factor" exists, which tends to weaken the pin-bone interface when hand drilling is performed. PMID- 1861046 TI - A detachable thumb spica for a rheumatoid brace. PMID- 1861047 TI - The influence of ethnicity, socioeconomic status, and psychological barriers on use of mammography. AB - This study assessed the relative influence of psychological barriers, SES, and ethnic differences in mammography use for a community sample of 586 White, 227 Black, and 150 Hispanic women. Confirmatory factor analyses with latent variables indicated plausible factor structures for all groups on items related to barriers to mammography. Summed indicators of SES, fear of radiation, embarrassment, pain, anxiety, and cost concerns were correlated significantly with mammography use for the pooled group. Separate analyses by ethnicity indicated a substantial relationship between mammography use and cost concerns by White and Black women, and fear of pain by Black and Hispanic women. Use of mammography was associated more highly with SES among Hispanic women. Pooled logistic regression analyses controlling for SES and ethnicity showed that the psychological barriers, especially concern about cost, remained important independent predictors of mammography use. We explore sociocultural explanations for less mammography use by Hispanic women, especially those less acculturated. PMID- 1861048 TI - Gender, time use, and health. AB - One of the continuing paradoxes facing social epidemiologists concerns sex differences in morbidity and mortality. Although women live longer than men, they apparently get sick more. We hypothesize that women's higher morbidity levels result from less paid work and lower wages combined with more hours spent in household labor, child care, and helping others, and fewer hours of leisure and sleep. Men and women hold different social roles; men hold most of the highly rewarding roles. We operationalize social roles as time commitments to various role-related activities. This approach provides interval-level measures such as time spent in caring for children instead of simple dichotomies such as parent/nonparent. We find that when gender differences in social roles are controlled, being male is associated with poorer health than being female. We conclude that if gender roles were more equal, women would experience better health than men, more consistent with their greater longevity. PMID- 1861049 TI - Adolescent women's contraceptive decision making. AB - A modified rational decision model incorporating salient events and social influences (particularly from sexual partners) is used to analyze adolescent women's consistent use of oral contraceptives (OCs) over a six-month period. Data are taken from a panel study of 308 clients of an inner-city family planning clinic. Expected OC use was computed for each subject on the basis of subjective expected utility (SEU) theory, and is found in multivariate analyses to be a significant predictor of actual OC use. In addition, variables representing baseline and follow-up partner influences, the salience of pregnancy for the subject, and positive side effects of OCs during the first months of use are found to predict OC use. Partner's support of OC use during follow-up and positive side effects of OCs are found to predict OC use among subjects for whom OC use was not the expected decision according to baseline SEU. Implications of the findings for models of adolescents' contraceptive behavior and for clinicians are discussed. PMID- 1861050 TI - The effects of maternal working conditions and mastery on child behavior problems: studying the intergenerational transmission of social control. AB - We assess the impact of maternal sense of mastery and maternal working conditions on maternal perceptions of children's behavior problems as a means to study the transmission of social control across generations. We use a sample of 521 employed mothers and their four-to six-year-old children from the National Longitudinal Survey's Youth Cohort in 1986. Regarding working conditions, we consider mother's hourly wage, work hours, and job content including involvement with things (vs. people), the requisite level of physical activity, and occupational complexity. We also consider maternal and child background and current family characteristics, including marital status, family size, and home environment. Maternal mastery was related to fewer reported behavior problems among children. Lower involvement with people and higher involvement with things, as well as low physical activity, were related significantly to higher levels of perceived problems. In addition, recent changes in maternal marital status, including maternal marriage or remarriage, increased reports of problems; stronger home environments had the opposite effect. We interpret these findings as suggesting how maternal experiences of control in the workplace and personal resources of control can influence the internalization of control in children. PMID- 1861051 TI - The effect of caregiver's burden on change in frail older persons' use of formal helpers. AB - We used a national longitudinal probability sample of frail older persons and their caregivers to examine three questions: 1) What are the probabilities of transition to use of formal helpers over a two-year period? 2) What is the role of predisposing, enabling, older person's need, and caregiver's need variables in changes in the use of formal helpers? 3) Do determinants of change in the use of formal helpers vary by level of caregiver's burden? Results show a slight trend to increased use in formal help over time. Personal burden, but not interpersonal burden, had a lagged effect on increased use of formal services. Use of formal helpers was greater in situations combining high levels of older person's need, high levels of caregiver's personal burden, and insufficient support from the informal network. PMID- 1861052 TI - Size and effectiveness of informal helping networks: a panel study of older people in the community. AB - This paper examines the impact over time of changes in older people's health and functional capacity on the size and effectiveness of their informal helping networks. Theoretical perspectives on networks differ in their predictions regarding the impact of declines in health on network size. Previous empirical studies have not examined the effects of changes in health on the size of networks. We examine empirical evidence on the impact of health changes on informal helping networks with longitudinal data obtained from a probability sample of older people living in the community. Results suggest that networks respond to diminishing health by increasing the scope of assistance provided but neither increase nor decrease in size as a consequence. The results also suggest that declines in functioning can produce increases in needs which exceed the capacity of informal networks. PMID- 1861053 TI - Damage to tissue defenses by EMLA cream. AB - EMLA is a new topical agent that safely anesthetizes intact skin. The purpose of this study was to determine if this cream could be safely used for anesthetizing wounds. This investigation evaluated the potential toxicity of EMLA cream in wounds by measuring its effect on host defenses and on the biology of wound repair. In contaminated wounds, EMLA cream elicited an exaggerated inflammatory response that damaged host defenses, inviting the development of infection. As a result of these investigations, we do not recommend the use of EMLA cream in wounds. PMID- 1861054 TI - A survey of emergency department communicable disease reporting practices. AB - A group of physicians, nurses, and administrators at all 11 hospitals in the District of Columbia were interviewed to elucidate each hospital emergency department's (ED) system for patient and public health notification of the diagnosis of legally reportable communicable diseases. The hospitals' reporting systems were divided into two groups. Three hospitals (27%) had reporting systems that were centered in the emergency department (EDS). Eight hospitals (73%) had disease reporting systems that depended primarily on extradepartmental personnel (HBS) for disease reporting. The EDS outperformed the HBS in several key areas of system performance. Greater attention needs to be paid by ED directors to assuring that their hospital's system is as accurate as possible and fulfills their jurisdiction's legal requirements for communicable disease reporting. PMID- 1861055 TI - Statistical concepts and methods for the reader of clinical studies in emergency medicine. AB - An understanding of statistical concepts and methods is essential for the clinician who wishes to interpret the results of clinical studies. In this article the concepts of descriptive statistics, classical hypothesis testing, P values, a priori information, and Type I and Type II errors are discussed with examples to illustrate their application to the interpretation of clinical trials. In addition, descriptions of Student's t test, the chi-squared test, Fisher's exact test, the rank sum test, and sequential methods are given. PMID- 1861057 TI - Splenosis: an unusual cause of intraabdominal hemorrhage. AB - A 31-year-old female presented to the emergency department with an acute onset of severe abdominal pain. She developed hypovolemic shock from an intra-abdominal bleed. At laparotomy she was found to be bleeding from two areas of splenosis on the uterine ligament. The patient had sustained a ruptured spleen 22 years prior and had no symptomatology from her areas of splenosis. A short review of splenosis is presented. PMID- 1861056 TI - Nontraumatic abdominal aortic thrombosis presenting with anterior spinal artery syndrome and pulmonary edema. AB - A 51-year-old woman with a history of breast cancer developed pulmonary edema and lower extremity paraplegia with preservation of proprioception as the initial manifestation of abdominal aortic thrombosis. Back pain was present in the lumbar region radiating to buttocks and legs in a bilateral radicular pattern. Femoral pulses were initially palpable. Aortic angiography revealed complete abdominal aortic occlusion at L3 as well as total occlusion of the bilateral superficial femoral arteries and bilateral common iliac arteries. Transient occlusion of the anterior spinal artery due to aortic thrombosis may cause paraplegia and may also progress to renal failure, bowel infarction, and limb loss if left untreated. Abdominal aortic thrombosis needs to be considered in a patient who presents with an anterior spinal artery syndrome, which, if present, must be treated as rapidly as possible to preserve motor and sensory function. PMID- 1861058 TI - Adrenal pheochromocytoma presenting with persistent abdominal and flank pain. AB - Pheochromocytoma is classically associated with paroxysms of headache and hypertension. Its presentation, however, may be more varied and subtle. We present a case of an adolescent female who complained of right upper quadrant and flank pain. A right adrenal pheochromocytoma was diagnosed and subsequently removed. The pertinent literature is discussed. PMID- 1861060 TI - Blow-out fractures: a review. AB - Blow-out fractures are a relatively common injury seen in the emergency department (ED). The diagnosis is based on clinical grounds, but defined radiographically. For the emergency physician, it is important to recognize the associated signs and symptoms in order that the diagnosis not be missed. Once the diagnosis is made, appropriate referrals need to be made. This article reviews diagnostic criteria, both clinical and radiographic, as well as an ED treatment protocol for blow-out fractures. PMID- 1861061 TI - Post-triathalon delirium. AB - This is a case presentation of acute delirium in a previously healthy man. It was originally discussed during Morbidity and Mortality Conference at The George Washington, Georgetown Residency Program in Emergency Medicine, December 1989. PMID- 1861059 TI - Midazolam use in the emergency department. AB - Midazolam is a new imidazobenzodiazepine derivative that is two to three times as potent as diazepam, is water-soluble, has a rapid onset and short duration of action, and produces a profound amnestic effect. These properties make it an extremely useful drug for outpatient sedation. We performed retrospective review of midazolam use in a general emergency department over a one-year period. Midazolam was used in 120 patients, 71 men and 49 women, with an average age of 46 years. The average dose given was 3.4 mg, with a range of 1 to 10 mg. In 69 of the cases (57%) other drugs were administered, most commonly an opiate. There were only four adverse reactions. One patient developed urinary retention, one patient vomited, and two patients were somnolent for a prolonged period of time. There were no serious cardiovascular or respiratory problems. We conclude that midazolam is a safe drug to use in the emergency department. Close monitoring of the patient and the availability of airway support equipment are mandatory. PMID- 1861062 TI - Nurses--the right to strike? PMID- 1861063 TI - The ethics of a professional strike. PMID- 1861064 TI - As the pendulum swings: the saga of physostigmine. PMID- 1861065 TI - Cellular telephones and disasters. PMID- 1861066 TI - Objectives to direct the training of emergency medicine residents on off-service rotations: critical care medicine, Part 2. AB - This article is the second of two parts outlining the objectives for resident rotations in intensive care units. It is part of a larger continuing series on the goals and objectives to direct the training of emergency medicine residents on off-service rotations. The critical care unit allows the resident an opportunity to provide continuing care for critically ill patients, many of whom enter the health care system through the emergency department. Critical care medicine is a natural continuum of emergency medicine, and provides the resident with the ability to follow the natural progression of seriously ill patients, as well as build confidence and experience in caring for the critically ill and injured. These objectives are designed to help focus the resident's reading and study during the rotation. PMID- 1861067 TI - Inhibition of antigen-driven proliferative responses and enhancement of antibody production during infection with Brugia pahangi. AB - Long standing Brugia pahangi infections in seven dogs, restricted to one rear limb popliteal lymph node and its afferent ducts, were monitored with regard to proliferative responses and antibody production specific for a PBS extract of B. pahangi (BpA) by cells from infected and uninfected lymph nodes and by PBL. Five of 10 dogs were negative for proliferative responses to BpA in node cells from infected limbs, yet they had positive PBL responses, and another was negative in both node cells and PBL. Production of BpA-specific antibody was detected in cultures of node cells from infected limbs of 9 of 10 dogs, but only in two cultures of node cells from uninfected limbs and not at all in PBL cultures. Three dogs with responsive node cells produced the least amount of anti-BpA antibody in culture. Injections of B. pahangi adult worm excretory/secretory products (ES), totaling 1 mg over 48 h, into the limb of the original infections in seven dogs, resulted in inhibition of Ag-driven proliferation by cell populations previously responsive to BpA. There was a loss of PBL responsiveness by all but one infected dog and a loss of node cell response by the two dogs previously responsive in infected and uninfected nodes. This loss of responsiveness lasted at least 28 days in three dogs. There was no evidence of suppression of responses to mitogens either before or after ES injection. In contrast, BpA-specific antibody production was greatly increased in node cells from infected limbs injected with ES. Similar injections into the uninfected limbs of two infected dogs produced no change of proliferative responses or of antibody production in the uninfected node. These results indicate that ES can modulate immune cell, Ag-driven proliferation, and simultaneously enhance antibody production in previously infected nodes. This may promote parasite survival by inhibiting cellular attack based on delayed-type hypersensitivity while directing immune responses toward production of antibodies that are less damaging to the adult helminth. PMID- 1861068 TI - Genomic organization and subchromosomal in situ localization of the murine granzyme F, a serine protease expressed in CD8+ T cells. AB - Granzyme F belongs to a closely related family of seven murine serine proteases stored in cytoplasmic granules of lymphoid cell populations. In contrast to the murine granzymes A to E and G, granzyme F is exclusively expressed in the CD4 CD8+ subset of peripheral T cells. To characterize the genomic sequences responsible for its highly restricted expression, we isolated a cosmid clone and sequenced a 7.5-kb genomic fragment that contains the promoter region and all five exons of the murine granzyme F gene. A TATA box sequence is located at position -25 relative to the transcription initiation site, which was determined by RNase protection. The genomic organization of granzyme F is similar to that of granzyme B and granzyme C, leukocyte elastase, cathepsin G, rat mast cell protease II, and complement factor D (adipsin). By the use of two fluorochromes for simultaneous high resolution in situ hybridization, the granzyme F gene was localized in close proximity distally from the TCR alpha-chain locus on mouse chromosome 14. PMID- 1861069 TI - DNA sequence polymorphism at the human tumor necrosis factor (TNF) locus. Numerous TNF/lymphotoxin alleles tagged by two closely linked microsatellites in the upstream region of the lymphotoxin (TNF-beta) gene. AB - TNF-alpha and lymphotoxin (LT, TNF-beta) genes are tandemly arranged and map within the MHC centromeric to HLA-B and telomeric to the class III genes. Both cytokines encoded by these genes are potent immunomodulators. On the other hand, some MHC-linked autoimmune diseases are characterized by abnormal levels of their expression or inducibility. A search for the putative disease-associated TNF/LT alleles depends on the informative genetic markers at the TNF locus. Previously, a low degree of genetic polymorphism at the human TNF locus has been reported, mostly bi-allelic RFLP. To localize and define additional polymorphic markers, we probed the collection of genomic clones with synthetic tandemly repeated dinucleotides, corresponding to the sequences known as microsatellites. We mapped and characterized three (TC/GA) and one (AC/GT) repeats within cloned 40-kb DNA comprising the human TNF locus. Using a polymerase chain reaction-based technique, we analyzed three of these four microsatellites and observed their length of polymorphism. Using DNA samples from blood donors, two families, and three human cell lines, we detected 13 distinct alleles of the AC/GT microsatellite neighboring human TNF genes. The variability was further increased by simultaneous analysis of the second linked microsatellite. This linked TC/GA repeat showed at least five alleles, whereas the least polymorphic TC/GA repeat located in the first intron of LT (TNF-beta) gene had two alleles. TNF alleles defined by microsatellites were stably inherited and segregated in the Mendelian way. Therefore, we describe thus far the most informative level of DNA sequence polymorphism in this part of human MHC. We propose a nomenclature for microsatellite tagged LT/TNF alleles based on their size and variability, which could also be extended to include RFLP and other not yet identified polymorphic markers. Microsatellite tagged polymorphism described here can be used in systematic linkage studies of HLA-associated diseases. PMID- 1861070 TI - Complete genomic sequence of the murine low affinity Fc receptor for IgE. Demonstration of alternative transcripts and conserved sequence elements. AB - The complete sequence of the murine low affinity Fc receptor for IgE (Fc epsilon RII), including the 5' and 3' flanking sequences, is reported. The murine Fc epsilon RII gene spans 12.9 kb and includes 12 exons surrounding 11 introns. The composite exon sequence is virtually identical to previously reported murine Fc epsilon RII cDNA sequences. Much of the proximal promoter regions of the mouse and human homologues of Fc epsilon RII show remarkable homology to each other, including three promoter elements previously identified for MHC class II genes. The reported exon/intron structure of the human FC epsilon RII is similar to the murine homologue, except that the latter has an additional exon coding for a fourth amino acid repetitive sequence (vs three in the human gene). RNase protection studies have identified an additional transcript within intron 2 of murine Fc epsilon RIIa, similar to the human Fc epsilon RIIb form but with a different predicted sequence of the first six amino acids. This transcript is present in the mRNA of purified splenic B cells, but not in the mRNA of the Fc epsilon RII+ B lymphoma cell line M12.4.5. The murine Fc epsilon RII gene contains a large intron (4.2 kb) separating the lectin and nonlectin coding regions, and several repetitive sequences are found clustered within this intron. These results emphasize the importance of the demarcation between these domains and allude to their evolutionary and functional significance. PMID- 1861071 TI - Human high molecular weight melanoma-associated antigen mimicry by mouse antiidiotypic monoclonal antibody MK2-23. Characterization of the immunogenicity in syngeneic hosts. AB - Previous studies have shown that the mouse antiidiotypic mAb MK2-23 elicited with the syngeneic anti-human high molecular weight melanoma-associated Ag (HMW-MAA) mAb 763.74 elicits anti-HMW-MAA antibodies in syngeneic hosts and in patients with melanoma. The present investigation has characterized the fine specificity of antibodies elicited by mAb MK2-23, tested its ability to induce delayed-type hypersensitivity reaction to HMW-MAA-bearing melanoma cells and analyzed the variables that influence the immunogenicity of mAb MK2-23. The anti-HMW-MAA antibodies elicited by mAb MK2-23 recognize the same population of molecules recognized by mAb 763.74, react with the same (or spatially close) determinant(s) and express the idiotopes recognized by mAb MK2-23 in their Ag-combining sites. The antiidiotypic antibodies that bind to HMW-MAA have a lower titer than those that do not. These results in conjunction with those obtained in mice using a suboptimal immunization schedule suggest that the idiotope(s) that mimic(s) the mAb 763.74-defined determinant of the HMW-MAA is less immunogenic than those that do not. mAb MK2-23 induces a delayed-type hypersensitivity reaction to HMW-MAA bearing melanoma cells. Therefore, mAb MK2-23 represents the first example of mouse antiidiotypic mAb that induces a cellular and humoral immunity to a human tumor-associated Ag (TAA), because the previously described mouse antiidiotypic mAb that bear the mirror image of TAA have been shown to induce only humoral anti TAA immunity. The immunogenicity of mAb MK2-23 is markedly enhanced by its conjugation to keyhole limpet hemocyanin and its administration with FA. Furthermore, the number of immunizations and the doses of mAb MK2-23 injected influence its immunogenicity, although to a lower extent than conjugation to a carrier and mixing with an adjuvant. The information derived from the present investigation represents a useful background to optimize the immunization schedule with mAb MK2-23 in patients with melanoma. PMID- 1861072 TI - Cloning and in vitro expression of a melanoma-associated antigen immunogenic in patients with melanoma. AB - The purpose of this study was to identify human melanoma-associated Ag (MAA) that are immunogenic in patients, because these molecules may be useful immunogens to implement active specific immunotherapy. To this end, an expression cDNA library constructed from the human melanoma cell line A375 was screened with sera from patients with melanoma. A 1029-bp cDNA (designated D-1) was isolated. Its nucleotide sequence showed no significant homology with viral and mammalian sequences stored in GE-NETYX. cDNA D-1 hybridized to a 2.0-kb mRNA species from human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cell lines but not from a renal carcinoma cell line, PBL, and cultured skin fibroblasts. The D-1 clone produced a fusion protein that displayed a significantly higher reactivity with sera from patients with melanoma than from healthy controls. Furthermore, D-1 fusion protein induced in mice antibodies that immunoprecipitated a 50-kDa component from cultured human melanoma cells. The structural properties of D-1 MAA are different from those of previously described MAA. These results suggest that the approach we have applied may be useful to identify novel MAA expressed by melanoma cells. Furthermore, the immunogenicity of recombinant D-1 protein suggests that it may be a valuable immunogen to implement active specific immunotherapy in patients with melanoma, if additional experiments show that it has the appropriate tissue distribution. PMID- 1861073 TI - Modulation of antigen presentation and peptide-MHC-specific, LFA-1-dependent T cell-macrophage adhesion. AB - Incubation of peritoneal macrophages in vitro before fixation increased their ability to present exogenous peptides to 3A9 T hybridoma cells. The enhanced level of presentation correlated with a greatly increased, peptide-specific adhesion of 3A9 cells to the macrophages, whereas peptide-independent adhesion was minimal and essentially unaltered. 3A9 cells exhibited rapid peptide-specific adhesion (plateau by 5 to 10 min) and deadhesion (complete reversal by 5 min). Peptide-specific adhesion was blocked by anti-I-Ak and anti-LFA-1. Interaction of T cell receptors and CD-4 with peptide-I-Ak complexes appeared to provide little direct contribution to the avidity of T cell-macrophage adhesion, but activated a LFA-1-mediated adhesion mechanism. In addition, anti-T cell receptor, anti-CD3, and anti-CD4 antibodies themselves activated LFA-1-dependent adhesion in the absence of peptide. Unlike the peptide-induced adhesion, this adhesion was similar for macrophages whether or not they were incubated in vitro before fixation. We conclude that the different macrophage populations supported LFA-1 mediated adhesion equally. Therefore, the enhancement of T cell stimulation observed after in vitro incubation of macrophages was due to increased peptide presentation and consequently increased triggering of LFA-1-mediated adhesion. Mechanisms may exist to regulate the effectiveness with which peptide-class II MHC complexes are displayed for T cell recognition. PMID- 1861075 TI - Cytotoxic T lymphocytes induce different types of DNA damage in target cells of different origins. AB - Nuclear changes may be important in the mechanism of CTL-mediated lysis. Rapid cleavage of target cell DNA into oligonucleosomes has been demonstrated as a very early event in CTL-mediated killing of murine hematopoietic targets. However, the results presented herein and by other investigators have shown that this extensive dsDNA fragmentation does not occur in all CTL targets. In terms of actual DNA damage, there is a wide range in the extent and type of DNA cleavage in various targets. Differences exist at both the species and the cell lineage level. The extent of DNA damage generally corresponds to the efficiency of lysis; thus, murine hematopoietic cells, which undergo dsDNA fragmentation, are killed more rapidly and at lower E/T cell ratios than are murine nonhematopoietic cells, which sustain single-stranded nicks. Experiments using cloned CTL demonstrate that the same effector cell kills both hematopoietic and nonhematopoietic targets, producing different types of DNA damage. These observations indicate that the fate of the target cell DNA is determined by the nature of the target cell and not by the CTL. We propose that DNA damage results from an enzyme pathway inherent to the target, which is activated by, not transferred from, the CTL. PMID- 1861074 TI - Natural killer cell clones can efficiently process and present protein antigens. AB - NK cell clones obtained from three different donors were tested for their ability to present soluble proteins to Ag-specific T cell clones. All NK clones were CD2+CD3-CD56+, whereas the expression of CD16 varied from clone to clone. The NK cell clones were able to process and present tetanus toxoid (TT) to TT-specific T cell clones in a class II HLA restricted manner. The capacity of NK cell clones to function as APC was also observed using the house dust mite allergen Der p I and the Der p I-derived peptide Val89-Cys117. As with EBV-transformed B cell line, NK cell clones could present the peptide 3-13 derived from the 65-kDa heat shock protein of Mycobacterium leprae, but they were unable to present the whole M. leprae Ag. Freshly isolated NK cells, IL-2-activated NK cells, and NK cell lines expanded in vitro could also process and present TT. The ability of the different NK populations to act as accessory cells correlated with their levels of class II HLA expression. These data demonstrate that NK cell clones can efficiently function as APC, however they may be restricted in the types of Ag that they can process. PMID- 1861076 TI - Characterization of autoreactive T cells. Relative importance of self-peptides versus MHC. AB - The degree to which processed self-peptides contribute to the stimulation of autoreactive T cells has not been determined. In this study we have analyzed a panel of autoreactive T cell hybridomas from normal C57BL/26 mice produced by fusing peripheral lymph node cells with a variant of the BW5147 thymoma line, which does not express endogenous TCR alpha- and beta-chains. All of the autoreactive hybridomas responded to spleen cells expressing the syngeneic I-Ab allele, but not to allogeneic spleen cells. Although all hybridomas were I-Ab restricted, they demonstrated different patterns of reactivity to a panel of APC expressing I-Ab but derived from different genetic backgrounds. In a panel of APC expressing recombinant I-A molecules, changes in the second half of the first domain, which encodes alpha-helix segments that flank the Ag binding site and directly contact the TCR V regions in proposed models, eliminated reactivity of all hybridomas tested. In addition, most of the autoreactive hybridomas also demonstrated inhibition of reactivity to mutations in the amino half of the first domain of the I-A alpha- and beta-chains, which encodes the beta-pleated sheet of the floor of the Ag-binding groove. To confirm the role of processed peptides in the different patterns of reactivity, APC were incubated with competitor Ag and fixed by glutaraldehyde cross-linking before incubation with the autoreactive T hybridomas. The hybridomas were effectively inhibited by exogenous protein and peptide Ag. These results indicate that processed self-peptides are required to activate the autoreactive T cells. PMID- 1861077 TI - Effect of nephritogenic antibody on complement regulation in cultured rat glomerular epithelial cells. AB - In passive Heymann nephritis, a rat model of membranous nephropathy, antibody (anti-Fx1A) activates C on the surface of the glomerular epithelial cell (GEC), leading to GEC injury and proteinuria. In this study, we examined C activation by anti-Fx1A in cultured rat GEC. In addition to anti-Fx1A IgG, anti-Fx1A F(ab')2 and Fab' led to GEC injury in the presence of rat or human sera as sources of C. Cytotoxicity was Mg2+ and factor B dependent, but Ca2+ independent, indicating that anti-Fx1A activated the C alternative pathway (AP). Furthermore, in the presence of Mg2+ and factor B, anti-Fx1A enhanced 125I-C3b deposition on GEC in the absence of classical pathway activation. AP C3 and C5 convertases formed on GEC (GEC-C3bBbP) were inactivated over time, probably due to binding of GEC C regulatory proteins. This inactivation was prevented when GEC-C3bBbP were incubated with anti-Fx1A IgG. An antibody raised against cultured GEC that binds to GEC in vitro and in vivo had no effect on C3 and C5 convertases, suggesting that stabilization of C3bBbP is unique to anti-Fx1A. Anti-Fx1A Fab' also stabilized GEC-C3bBbP, indicating that cross-linking of membrane Ag was not required. C3bBbP on E were not affected by anti-Fx1A, excluding direct stabilization of convertases by anti-Fx1A. Therefore, anti-Fx1A inhibits C regulation on GEC, which can account for its ability to activate the AP. This represents a potentially powerful mechanism of producing disease in vivo. PMID- 1861078 TI - Differentiation-inducing cytokine P48 exists in a membrane-associated form. AB - P48 is a recently described 48-kDa differentiation-inducing cytokine isolated from the culture medium of the human leukemia line Reh. P48 induces differentiation and cytolytic activity in the promyelocytic cell line HL-60, and stimulates the release of TNF-alpha and IL-1 from peripheral blood monocytes. In further studies designed to examine the biosynthesis and function of P48, surface immunofluorescence flow cytometry analysis as well as 125I surface labeling and immunoprecipitation, revealed the presence of P48 on the surface of Reh cells. Triton X-114-treated Reh cells were partitioned into detergent and aqueous phases and separated by SDS-PAGE. Western blot analysis revealed that P48 partitioned exclusively into the detergent phase, suggesting an integral membrane association. Reh cells fixed with paraformaldehyde, but not K562 or P815, were able to stimulate the release of TNF-alpha from peripheral blood monocytes in a manner similar to that of secreted P48. Isolated plasma membranes from Reh cells could also stimulate TNF-alpha release. This TNF-alpha-releasing activity could be removed from detergent solubilized Reh membranes by immunoaffinity chromatography on an anti-P48 column. This study suggests that, in addition to being secreted into the culture medium, P48 is expressed on the surface of Reh cells in a biologically active form. The membrane form of P48 may be 1) a final maturation step before secretion or 2) a cell membrane-associated form that may be analogous to the membrane forms of TNF-alpha and IL-1. PMID- 1861079 TI - Detection of in ovo derived idiotypic antibodies. I. A model for maternal neonatal idiotype network studies. AB - Idiotypic vaccines appear to have many advantages over conventional vaccines. Maternal Id or anti-Id that are passively transferred to the fetus or neonate could provide another avenue for vaccination. Based on this premise we have investigated the transmission of idiotypic antibodies from dam to embryo by inoculating laying hens and analyzing their egg yolks for the presence of Id, anti-Id, and anti-anti-Id. The Ag chosen for these studies was BSA. After isolation and concentration BSA Id titers were approximately 256,000. The presence of anti-Id antibody in yolk samples is characterized by the ability of anti-Id to inhibit BSA binding to Id. The anti-Id extracted from yolks inhibited BSA binding to Id by 7 to 53%. Not all of the anti-Id present in samples was binding to a paratope-associated Id because 11 to 16% of the fluoresceinated anti Id bound to Id-coated beads in the presence of excess BSA. Because a portion of the anti-Id antibodies were internal images of the BSA Id, they should be able to mimic Ag. This idea was confirmed when anti-Id inoculated in hens caused the synthesis of antibodies that would bind BSA and could be detected in an ELISA. Binding of anti-anti-Id to BSA-coated wells could be inhibited by preincubation of anti-anti-Id with BSA in solution. The chicken model provides a novel system to investigate maternal-fetal and maternal-neonatal interactions in the idiotypic network and the cellular mechanisms involved in the ontogeny of the Id network in neonates. PMID- 1861080 TI - Proteolysis of C3 on U937 cell plasma membranes. Purification of cathepsin G. AB - Covalent binding of C3 fragments to U937 cell membranes involved a cell surface associated proteolytic activity. Two proteases able to cleave C3 were purified from U937 plasma membranes. Purification involved solubilization of the membranes and ion exchange chromatography. One of the purified proteases was identified as elastase, based upon a substrate specificity for benzyloxycarbonylalanine-o nitrophenyl ester and complete inhibition by elastatinal and methoxysuccinyl alanyl-alanyl-prolyl-valyl-chloromethyl-ketone. The other protease (m.w. 28,000) is cathepsin G, as deduced from the amino acid composition, the amino-terminal sequence, and the substrate specificity for succinyl-alanyl-alanyl-phenylalanine p-nitroanilide. These two lysosomal proteases are present on the U937 cell surface, as confirmed by immunofluorescence analysis. Plasma membrane elastase and cathepsin G from U937 cells cleave C3 into C3a- and C3b-like fragments; further incubation leads to C3c- and C3dg-like fragments, as judged from SDS-PAGE analysis of the digests. Sequencing of the C3b-like fragment purified by reverse phase chromatography indicates that initial cleavage of C3 by purified cathepsin G occurs at two positions in the amino-terminal part of the alpha-chain, at a Arg Ser bond located between residues 748 and 749 and at a Leu-Asp bond between residues 751 and 752. These proteases are, thus, able to generate, on the U937 surface, active fragments of C3, which are likely to be involved in cell-protein and cell-cell interactions. PMID- 1861081 TI - A covalent dimer of complement C4b serves as a subunit of a novel C5 convertase that involves no C3 derivatives. AB - A C intermediate, LAC14, was prepared from TNP-aminocaproyl liposomes sensitized with anti-TNP antibody (Ab) and purified human C1 and C4. LAC14, containing radiolabeled C4, was analyzed by SDS-PAGE followed by autoradiography, and yielded a 210-kDa band and a predominant 400-kDa band. The 210-kDa band consisted of monomeric C4b bound to low molecular mass acceptors. The 400-kDa band was comprised of a 200-kDa moiety, as well as beta- and gamma-chains of C4. The 200 kDa moiety contained neither C1 nor sensitizing Ab, but it was largely decreased by treatment with NH2OH to the 90-kDa moiety with the mobility corresponding to the alpha'-chain of C4b. A covalent dimer of C4b, therefore, is the predominant form of C4b deposited on liposomes sensitized with antibody. The C4b-C4b dimer formed rapidly (within 5 min) followed by slow dissociation into monomers. The LAC14 bearing the C4b dimer but not the monomer was lysed, although with relatively low efficiency, by the addition of oxyC2 and EDTA-supplemented C3 deficient serum (C3DS), and, furthermore, LAC142 possessed the ability to convert C5 into C5a and C5b. Moreover, lysis was inhibited not by anti-C3 Ab but by anti C4 Ab. In other experiments, the dimer served as an element of C3 convertase, as well. These findings imply that the C4b dimer, when complexed with C2, expresses C3/C5 convertase activity without participation of C3, and may provide a molecular mechanism whereby sera from patients with complete C3 deficiency retain the ability to induce C-mediated cytolysis. PMID- 1861082 TI - Generation and specificity of monoclonal anti-idiotypic antibodies against human HIV-specific antibodies. I. Cross-reacting idiotopes are expressed in subpopulations of HIV-infected individuals. AB - In this study we have generated monoclonal anti-idiotypic antibodies against human monoclonal and polyclonal anti-HIV antibodies in seropositive sera. A human anti-gp41 mAb (H2, IgM kappa) was used to immunize BALB/c mice and to prepare hybridoma anti-antibodies that react with H2 and not with normal human IgM. Similar monoclonal anti-antibodies were made in BALB/c mice immunized with Ig fraction prepared from a pool of HIV-seropositive sera. Both kinds of anti idiotypic antibodies reacted with antibodies in pools of seropositive sera and with individual seropositive sera but not with normal human Ig or seronegative sera. The Id-positive Ig from single donors were isolated on two different anti Id immunoabsorbents and shown to bind to p24 and gp120, respectively. The detection and isolation of idiotypically cross-reactive human anti-HIV antibodies from seropositive donors demonstrated, for the first time, the existence of shared Id expressed by antibodies against HIV Ag. The utility of cross-reacting anti-idiotypic antibodies as tools to dissect the network regulation of the anti viral immunity in AIDS is discussed. PMID- 1861083 TI - Natural killer cell cytolytic granule-associated enzymes. I. Purification, characterization, and analysis of function of an enzyme with sulfatase activity. AB - An enzyme with sulfatase activity has been isolated from the granules of a rat NK leukemia cell line, CRNK-16. The enzyme has been purified from crude preparation, with a specific activity of 52 nmol/min/mg of protein, by DEAE ion exchange and Con A-Sepharose affinity chromatography, resulting in a specific activity of 230 nmol/min/mg of protein. The molecular mass of the purified enzyme was estimated to be 40 kDa by gel filtration chromatography at pH 7.4, but the enzyme had the ability to complex to molecular masses of greater than 300 kDa at low pH when crude granule extract was used as the starting sample, suggesting that it associates with other granule components. The enzyme was determined to be an arylsulfatase by its ability to (a) hydrolyze p-nitrophenyl sulfate (Km = 26.0 mM) and p-nitrocatechol sulfate (pNC sulfate) (Km = 1.1 mM) and (b) be inhibited by sulfite (Ki = 6.0 x 10(-7) M), sulfate (Ki = 1 x 10(-3) M), and phosphate (Ki = 4 x 10(-5) M) in a competitive manner. The pH optimum for enzymatic activity was determined to be 5.6. The role of this enzyme in cytolytic function was investigated by examining the effect of its substrates and inhibitors on granule- and cell-mediated lysis. pNC sulfate was shown to cause a dose-dependent inhibition of target cell lysis by isolated cytolytic granules (complete inhibition at 12.5 mM). Sulfite induced an incomplete inhibition (50% at 1 mM), whereas phosphate was essentially without inhibitory effect. Sulfate, on the other hand, altered lytic activity in a biphasic manner, inasmuch as it induced an inhibition of lysis at high concentrations and an increase of lysis at low concentrations. Cell-mediated lysis was inhibited by pNC sulfate in a dose dependent fashion at concentrations greater than 2.5 mM, with nearly complete inhibition at 50 mM. Sulfate also altered the lytic activity by intact cells in a biphasic manner, although the effect was much less pronounced. Sulfite and phosphate caused only a 30% inhibition of lytic activity. These results suggest that the sulfatase enzyme is involved in NK cytolytic function, presumably at the lethal hit stage. PMID- 1861084 TI - Bronchial epithelial cells release monocyte chemotactic activity in response to smoke and endotoxin. AB - An increase in mononuclear phagocytes occurs within the airways during airway inflammation. Bronchial epithelial cells could release monocyte chemotactic activity and contribute to this increase. To test this hypothesis, bovine bronchial epithelial cells were isolated and maintained in culture. Bronchial epithelial cell culture supernatant fluids were evaluated for monocyte chemotactic activity. Epithelial cell culture supernatant fluids attracted significantly greater numbers of monocytes compared to media alone and the number of monocytes attracted increased in a time dependent manner. Endotoxin and smoke extract induced a dose and time dependent release of monocyte chemotactic activity compared with cells cultured in media (52.5 +/- 2.6 (endotoxin), 30.5 +/ 2.3 (smoke) vs 20.5 +/- 2.2 cells/high power field (HPF) p less than 0.001). The released activity was chemotactic by checkerboard analysis. Stimulation of the epithelial cells by opsonized zymosan, calcium ionophore (A23187), and PMA also resulted in an increase in monocyte chemotactic activity (p less than 0.01). Because the release of activity was blocked by the lipoxygenase inhibitors, nordihydroguaiaretic acid and diethycarbamazine, epithelial cell monolayers were cultured with 3 microCi [3H]arachidonic acid for 24 h and then exposed to A23187, PMA, or both stimuli, for 4, 8, and 24 h. Analysis of the released 3H activity was performed with reverse-phase HPLC and revealed that the major lipoxygenase product was leukotriene B4. These data suggest that monocytes may be recruited into airways in response to chemotactic factors released by bronchial epithelial cells. PMID- 1861085 TI - Management of symptomatic bilateral internal carotid artery occlusion and vertebral artery stenosis. AB - This report presents a patient with bilateral internal carotid occlusion and concomitant vertebral artery stenosis. His lateralized amaurosis fugax, syncopy and partial visual field defect resolved following open external carotid endarterectomy, onlay patch external carotid angioplasty with endarterectomized internal carotid artery and vertebral artery transposition to the common carotid artery. PMID- 1861086 TI - Giant aneurysm of the coronary artery. AB - A case of a patient presenting a giant size mass compressing the SVC and IVC is presented. Chest X-ray, substernal echo-scanning, magnetic resonance tomography, etc. led to the hypothesis of a benign cardiac tumor or cardiac echinococcosis. However, surgical examination revealed a giant aneurysm of the coronary artery which was successfully treated. PMID- 1861087 TI - Superficial venous thrombosis of the lower extremities co-existing with deep venous thrombosis. A phlebographic study on 57 cases. AB - The incidence of deep venous thrombosis (DVT) coexistent in patients suffering from superficial venous thrombosis (SVT) has not been well documented. In a series of 57 consecutive patients with SVT of the lower extremities treated in our Department in the last five years without any obvious clinical signs of co existing DVT, an ascending phlebographic study was performed. Co-existent DVT was disclosed in 19.6% of the patients. There was no correlation between the location or the length of thrombus and the co-existence of DVT. Patients in whom SVT developed in existing varicose veins were younger in age and the incidence of co existence of DVT was lower. Our findings show that SVT does not always have a benign course. The disclosure of a high incidence of co-existing DVT in our series suggests the necessity of the examination of the deep venous system in all the cases of SVT by using ultrasonic technics, triplex and preferably of the ascending phlebography. The disclosure of DVT in those cases makes the application of anticoagulant treatment mandatory. PMID- 1861088 TI - Frequency of malignant diseases in deep venous thrombosis of the lower extremities. AB - A retrospective investigation was carried out in a total of 200 patients (100 women, 100 men) with an average age of 61.0 years (19-97 years) with a phlebographically verified deep vein thrombosis of the lower limbs. It was examined whether and how frequently acute phlebothromboses are associated with a malignant underlying disease not detected up to that time. Specific diagnostics showed that a malignancy could be detected in 11.5% of all patients. As expected, the number of freshly discovered malignant diseases rose with increasing age. Seventy-one percent of all patients with a phlebothrombosis and a simultaneous tumor condition were more than 60 years old. The results clearly show that screening for occult malignant diseases should be carried out systematically and routinely in patients with etiologically unclear acute deep vein thromboses, at least from the 50th year of life onwards. PMID- 1861089 TI - Assessment of the patency of deep leg veins with duplex. AB - To evaluate the accuracy of venous duplex, results obtained in 101 patients are compared with venography. A first group consisted of 48 patients with clinically suspected deep vein thrombosis. In 30 of them a positive duplex scan was obtained and all had subsequently a positive venography. Eighteen patients with a normal duplex scan had a normal venography. Another group of 53 patients were tested preoperatively for varicose vein surgery. No obstruction of the venous system was withheld with duplex but 3 patients had an old thrombosis on venography. Thus duplex is a highly reliable method to detect proximal thrombosis in clinically suspected patients but detection of late sequelae of thrombosis may be more difficult. PMID- 1861090 TI - Comparison of skin and muscle biopsies before and after pentoxifylline treatment in patients with leg ulcers due to deep venous incompetence. AB - The aim of this study was to understand the possible mechanisms by which deep venous insufficiency and venous hypertension are associated with trophic skin changes and ulceration and to explain the therapeutic effect of Pentoxifylline in patients with leg ulcers due to deep venous incompetence. Twenty patients were included in this pilot study. They were graded into two groups: group 1, included 10 patients (5 F and 5 M) with deep venous incompetence and normal arteries; group 2, included 10 patients (1 F and 9 M) with deep venous incompetence and moderate arterial disease. Skin and muscle biopsies were carried out before and after the oral administration of 1,200 mg of Pentoxifylline daily (400 mg t.d.s). The following parameters were investigated by means of light microscopy and immunofluorescence tests: engorgement of venous stroma; decrease of intimal elastica; hyaline degeneration; floccular degeneration; pericapillary fibrin deposits and fibrin degradation products; inflammation and fat necrosis; myofibril degeneration; fibrous scar; regeneration and reconstitution of muscle fibres. The results indicated that local inflammation at the ulcer's area cause accumulation of white blood cells in the capillaries and the interstitial fluid, where there is also accumulation of fibrinogen. These changes may lead to chronic tissue ischaemia and ulceration. The known favourable effect of Pentoxifylline on red cells and leucocyte function as well as its lowering effect on plasma fibrinogen level, may be responsible for the observed therapeutic effect of Pentoxifylline on venous leg ulcers. PMID- 1861091 TI - Free radical production in peripheral vascular disease. A risk for critical ischaemia? AB - Malondialdehyde (MDA) plasma concentrations (marker of lipid free radical peroxidation) and the unfractionated leucocyte and erythrocyte filterability rates (through 5 micron Nuclepore filters in a positive pressure filtration system) were determined during a partial ischaemia induced by two consecutive treadmill tests in 64 stage II peripheral vascular disease (PVD) patients and in 32 matched controls. Transcutaneous oxygen pressure (tcPO2) was monitored constantly throughout the walking tests and recovery periods. In the PVD patients impairments in the flow properties of leucocytes and erythrocytes were associated with increases in MDA plasma concentrations which correlated significantly with a lengthening of the tcPO2 half recovery times--index of the worsening of ischaemia. Patients could be divided into two sub-groups on the basis of these impairments and their half recovery times, suggesting this experimental model may provide a means to identify those stage II PVD patients most likely to develop critical limb ischaemia. PMID- 1861092 TI - Heparin, heparin plus ASA and dipyridamole, and arteriovenous fistula as adjuvant methods to prevent rethrombosis after venous thrombectomy. Experimental study in rabbits. AB - Venous rethrombosis following thrombectomy is a common event. The aim of the present study was to verify the action of heparin, heparin plus acetyl salicylic acid (ASA) and dipyridamole, and of an arteriovenous fistula (AVF) in the prevention of this complication. Thrombosis was induced in 48 male rabbits by the injection of thrombin in a segment of the left jugular vein, in which the blood flow was arrested for 10 minutes. After 48 hours, the animals were randomly allocated into one of 4 groups of treatment: (1) control, (2) subcutaneous heparin (600 S.I. Units/kg--8/8 hours), (3) heparin, in the same dose, plus ASA (10 mg/kg/once a day), and dipyridamole (0.5 mg/kg thrice a day), (4) an AVF was surgically constructed between the left carotid artery and the left maxillar vein. After 30 minutes, thrombectomy was performed. The venous blood flow, the hematocrit, activated partial thromboplastin time and thrombin time tests were performed before, right after the thrombectomy and 48 hours after thrombectomy. Venography was performed after thrombectomy and at the end of the experiment. The animals were killed 48 hours after thrombectomy and the veins were examined macroscopically. Venous rethrombosis was significantly prevented only in the AVF group (9/12), when compared to control group (0/12), heparin group (1/12) and heparin plus antiaggregating agents group (2/12). These results validate further clinical and experimental investigations with the use of AVF to prevent rethrombosis after venous thrombectomy, when a reduction of venous flow is present. PMID- 1861093 TI - Management of vascular injuries of the extremities. One hundred and fifteen cases. AB - In between the years 1984-1989, 115 peripheral arterial injuries were admitted to the Emergency Surgical Unit of Istanbul Medical Faculty. Seventy-two patients (62%) had upper extremity and 43 patients (38%) had lower extremity vascular injuries. Twenty-eight of these cases (24%) were due to blunt trauma, angiographic studies were obtained in 26 patients. There were 9.5% mortality and 7% amputation rate. We conclude that arterial injuries deserves early recognition, rapid fixation of osseous injuries, wide debridement, fasciotomy in blunt injuries and proper antimicrobial therapy. PMID- 1861094 TI - Cardiovascular disease in women: an update. AB - Between the years 1979 and 1981, Louisiana ranked 7th in average annual coronary heart disease (CHD) death rate among white women and 6th among black women, age 35 to 74 years. Nationally, death in women due to CHD is 250,000 deaths per year, mainly in women over 50 years of age. That is approximately one half of all deaths due to heart disease in the United States. Risk factors for CHD in women are those which are shared with men, eg, smoking, hypertension, plasma lipoprotein concentrations, obesity, diabetes, and family history, and those which apply solely to women, eg, contraceptive use, menopause, and postmenopausal hormones. The purpose of this manuscript is to review current knowledge regarding CHD in women. PMID- 1861095 TI - ECG of the month. Where the action is. Paroxysmal atrial fibrillation. PMID- 1861096 TI - Estrogen therapy and cardiovascular risk in women. AB - Estrogen therapy in women has traditionally been used for the relief of menopausal symptoms and protection from osteoporosis. Recently, there has been a growing body of evidence suggesting that estrogen therapy protects against cardiovascular disease in women. An epidemiologic review of the literature demonstrates an approximately 50% reduction in cardiovascular risk in women using estrogen. A brief review of indications, complications, and routes of estrogen administration is presented. Current areas of controversy include the effects of parenteral estrogen administration and progestin administration on the cardioprotective aspects of estrogen therapy and the risk of breast cancer in estrogen users. Further study in these areas is needed. PMID- 1861097 TI - Mitral valve prolapse. AB - Mitral Valve Prolapse (MVP) is a common cardiac disorder in our community. It is estimated that 4% to 15% of the general population have the anatomical defect of prolapsed mitral valve leaflets during ventricular systole. Patients with MVP that suffer from chest pain, dyspnea, fatigue, dizziness, syncope, palpitations, cardiac arrhythmias, anxiety, and panic attacks are diagnosed as having Mitral Valve Prolapse Syndrome. There is much controversy in the medical literature as to the causes of MVPS symptomatology. Some scientists believe that autonomic dysfunction, adrenergic, and vagal responsiveness are factors which appropriately explain the symptoms of MVPS. Pharmacological therapy, depending on the severity of the symptoms, is one option for treatment. Education on the etiology of their symptoms, instruction on lifestyle modifications, and reassurance from their physician are appropriate methods for the management of MVPS patients. PMID- 1861098 TI - Peripartum cardiomyopathy: clinical and therapeutic characteristics. AB - Peripartum cardiomyopathy occurs in from 1 in 3,000 to 1 in 4,000 pregnancies in the United States. Its clinical and hemodynamic findings are similar to idiopathic dilated cardiomyopathy; however, peripartum cardiomyopathy shows a high incidence of myocarditis. Future studies will define the role of immune factors associated with the development of this disorder and will help in a better outcome for these patients. PMID- 1861099 TI - Pediatric sinusitis: diagnosis and management with endoscopic techniques. AB - Sinusitis in children has recently received more attention as a possible etiology in chronic or persistent cough, chronic nasal congestion, purulent rhinorrhea, and generalized malaise. Its association with upper respiratory infections and allergy is still sometimes overlooked, however, resulting in prolonged but often inadequate treatment for the young patient. An attempt to better define the anatomy and physiology of the paranasal sinuses, along with a discussion of etiologies and diagnostic and therapeutic techniques, will provide some useful information in the management of this problem. PMID- 1861100 TI - [Value of axillofemoral bypass in the elderly]. AB - The aim of this retrospective study was to assess the merits of axillofemoral bypass in elderly patients. 69 axillofemoral grafts were laid from 1981 to 1985 in 56 patients, all older than 70. They always were aimed at limb salvage due to aortoiliac obliterating lesions (the indications of sepsis of aorto-bifemoral prostheses have been excluded). 13 patients have had an axillo-bifemoral graft and 43 an unilateral axillofemoral graft. The lower anastomosis involved the common femoral artery in 30 cases, the deep femoral artery in 39. The patients were followed up for 1 to 74 months, with an average of 24 months. The operative mortality was of 10 cases (17%). During the first postoperative month, 3 major amputations were required. The cumulated survival rate at 60 months was of 18%, with the primary and secondary patency rates at 60 months being of 46% and 71%, respectively. We conclude that axillofemoral bypass is perfectly adapted to this population of elderly subjects, in whom a direct aortic approach is counterindicated. PMID- 1861101 TI - [The angiologist and angiology in Switzerland]. PMID- 1861102 TI - [Sequelae of venous thrombosis. Incidence in of the post-thrombosis syndrome after 5 years]. AB - The authors report on an epidemiological study carried out in Basle, Switzerland, which prospectively included 341 consecutive patients (226 men, 115 women, mean age 52 +/- 16 years) who had developed deep venous thrombosis evidenced by phlebography. The treatment of the acute phase most often consisted in thrombolysis, conventional heparin being reserved for the contra-indications of thrombolysis. A second phlebographic examination allowed dividing up the series into two groups, ie. positive and negative, according to the presence or absence of a complete or partial return of patency. Each group was subdivided according to the location and extension of the thrombosis. Both groups (positive vs. negative) are different as regards the location and extent of the thrombosis. The selective comparison of both groups according to the objective subdivision demonstrated: the absence of post-phlebitis disease in sural phlebitis; the same risk of post-phlebitis disease in thrombosis extending to 4 levels, whether patency was restored or not; lower incidence of post-phlebitis disease in the positive group for single -, two - or three-level phlebitis. Leg ulcers occur within an average of 5.5 +/- 2.1 years after the acute episode in 6.7% of all patients. Complete return of patency is obtained in 23% of cases only. PMID- 1861103 TI - [Ambulatory phlebectomy by the Muller method: technique, advantages, and disadvantages]. AB - Phlebectomy according to Muller is a simple and efficient method. A very narrow incision (1 to 2 mm) makes it possible to grasp the varicose vein with a small hook and to extract it. Indications are numerous: varices of the trunk (without insufficiency of the great saphenous vein junction), perforating varices, reticular varices, nutrient veins of telangiectasias or of leg ulcers, unsightly veins (in the eyelids, arms, etc.). There are numerous advantages of phlebectomy according to Muller. In terms of ambulatory patients, it is a simple technique free of risks (especially thromboembolic ones) for surgical treatment of all types of varices. This technique is particularly economical (simple infrastructure, little loss of patient work time). Elective extirpation of varicose veins allows the healthy venous trunks to be conserved (reconstructive surgery) and scars are practically invisible. In terms of hospital practice, this technique has been adopted by numerous surgeons as a complement to resection of the sapheno-femoral junction and stripping, thus permitting reduction of scar size and extirpation of the narrowest varices. The drawbacks are minimal: the usual complications of any surgical technique and too easy accessibility to the poorly trained practitioner. PMID- 1861104 TI - [Characteristic contributions of the venous duplex exam]. AB - The major advantage of non invasive duplex scanning is the ability to combine its imaging capability (information on the morphology) with the possibility to detect Doppler spectra (hemodynamic information) of the visualised segment. This new method, mainly used for the investigation of arterial diseases, is more and more applied in phlebology too. The technique is very reliable in the diagnosis of deep vein thrombosis and in the investigation of varicose veins and their junctions with the deep venous system. In these indications duplex scanning is likely to become a standard technique. The use of duplex in phlebology, however, should not be limited to these indications. In this paper the results of some special phlebologic duplex studies are presented: A) changes in the subclavian vein induced by pace maker electrodes; B) utility in the differential diagnosis of deep vein thrombosis; C) efficacy in the control of caval filter; D) measurements of physiologic venous hemodynamics and quantification of phlebologic drug effects. PMID- 1861105 TI - [Value of the plasma measurement of D-dimers in the diagnosis of venous thromboembolism]. AB - Plasma measurement of D-dimers (DD), which are fibrin-specific degradation products, progressively replaces the cumbersome dosage of fibrinogen degradation products (FDP's) in serum for diagnosis and follow-up of consumption coagulopathies, for diagnosis of prethrombotic states and, potentially, for the control of the efficacy of antithrombotic therapies. Moreover, when the ELISA technique is used, this measurement may be very useful in the diagnosis approach of venous thromboembolic disease. In the present review, data are presented which strongly support the view that a low level of plasma D-dimers (less than 500 micrograms/L when using the ELISA from Stago) allows to exclude the diagnosis of deep venous thrombosis or pulmonary embolism with predictive values of 94 % and 100 % respectively. It is suggested that such a diagnostic potential might be very useful in the group of patients with inconclusive perfusion-ventilation scintigraphy (low or indeterminate probability of pulmonary embolism) which represent about 50 % of the patients with suspected pulmonary embolism. PMID- 1861106 TI - Ambulatory care for ambulant patients with deep vein thrombosis. AB - A follow-up study is reported on 49 patients with acute deep vein thrombosis (DVT) treated on an ambulatory basis. Venography had shown crural DVT in 27 % and proximal extension in 73 %. The initial treatment consisted of heparin (7,500 U iv, 40,000 U sc), ethylbiscoumacetate (900 mg), phenprocoumon (9 mg), and a ready made compression stocking for the calf. The patients were advised to undertake frequent strolls, the first when leaving the office. Pain, swelling and incapacity for walking vanished within two days. The partial thromboplastintime was prolonged 2.4-times on the first day and the thromboplastintime was in the therapeutic range on the second day already. Until follow-up 4 patients died of other diseases. There was no clinical pulmonary embolism, no secondary hospitalisation and only one new DVT. Of 844 months of patients at risk of recurrence 50 % passed under anticoagulants and 70 % with compression therapy. At an average of 19 months, 82 % of patients were asymptomatic and 45 % showed mild chronic venous insufficiency. In contrast, impaired drainage function (by lightreflectionrheography) was found in 79 % overall and in 100 % after DVT of the proximal veins. The discrepancy is explained by the compliance with compression therapy. PMID- 1861107 TI - [Surgical treatment of varices at the stage of trophic disorders in chronic venous insufficiency]. AB - Most ulcers of the lower limbs are caused by existing chronic venous insufficiency. Later on, true social and professional problems will arise, with serious economic and psychological consequences not only for the patient himself, but for the community as well, such as huge medical costs--hence the importance of prevention and treatment, which must in no case be purely symptomatic. The ligation of the arch and of the perforating veins and stripping of the affected vein are part of the classical management of varices. These procedures can may prove to be virtually impossible in case of chronic venous insufficiency, if the patient also presents with subcutaneous liposclerosis or atrophy in an already pregangrenous skin. This preulcerous stage can be aggravated later on if the requirements for surgical repair are not met. Necrosis can then occur, if too aggressive surgery directly or indirectly injures the microcirculatory system of the damaged skin. Omitted or undesirable acts are dangerous at the stage of trophic disorders and surgery may fail to reach its aim, which of course would be to definitively and quickly eliminate the varicose disease. PMID- 1861108 TI - [Pseudo-Kaposi syndromes of vascular origin]. AB - Pseudo-Kaposi's Sarcoma with vascular disease concern mainly acroangiodermatitis described by Mali--(with chronic venous insufficiency)--, arteriovenous malformations with angiodermatitis described by Stewart and Bluefarb, and pseudo Kaposi's Sarcoma occurring after placement of arteriovenous shunt for hemodialysis. Search for relation ships between classical Kaposi's Sarcoma and new AIDS Kaposi's Sarcoma explains new interest devoted to Pseudo-Kaposi's Sarcoma. PMID- 1861109 TI - [Kaposi's sarcoma associated with acquired immunodeficiency syndrome]. AB - AIDS-related Kaposi's sarcoma (KS) accounts for 15-20% of cases of AIDS. Clinical presentation is similar to that of classical KS but with an overall more aggressive evolution and cutaneous dissimilation. There is no particular predilection for the lower limbs and frequent lesions are located on the face. Most of the cases have occurred in homosexual males with a moderate immune deficiency (mean CD.4 = 300/mm3). This predilection for gay people has not yet received explanation and the physiopathology of KS is unclear. Treatment of KS with interferon or chemotherapy (Bleomycin) is effective in 30-50% of cases. PMID- 1861110 TI - [Visceral involvement in Kaposi's sarcoma associated with the acquired immunodeficiency syndrome]. PMID- 1861111 TI - [Kaposi's syndrome following transplantation]. AB - Kaposi's sarcoma has particularly been described after renal transplantation. More recently, a number of cases have been reported after hepatic or cardiac transplantation. The fostering factors are the same as for the other Kaposi's sarcomas, while the HIV1 or HIV2 serology is always negative. Renal transplantation may increase the natural risk of Kaposi's sarcoma by a factor of 4 to 500. The immunodepressive treatment must be reduced in case of purely cutaneous Kaposi and interrupted in case of visceral involvement. Death generally occurs as a consequence of infections. Kaposi's sarcoma after heart transplantation has a poorer prognosis, with fatal evolution in the four cases observed out of the 967 cardiac transplantations performed in the Ile-de-France region from 1968 to 1990; the cause of death most often is graft rejection or an infection. PMID- 1861112 TI - [Necessity of reconciling the objectives of the treatment of varices and arterial surgery. Practical consequences]. AB - It is unwise to treat patients with varicose veins without thinking about the possibility of atherosclerotic disease occurring later on. The various procedures of stripping, as well as cryosurgery and sclerosis injections in the saphenous veins destroy veins which are at present the best material for femoro-tibial, femoro-popliteal and coronary bypass. Every year, a great deal of limb salvages cannot be achieved because saphenous veins have been previously removed. As arterial disease occurs one or several decades after the venous complaint, every patient with varicose problems may be concerned. Further more, contrary to a frequent opinion, great saphenous veins of varicose patients are often suitable for arterial bypass. As Doppler combined to duplex scan allow to draw a precise map of the superficial venous channels with their endings, amount of flow back, and caliber of the saphenous veins, it is now possible to propose to most patients conservative procedures: ambulatory phlebectomy or sclerosis injections of peripheral veins in case of minor reflux, crossectomy or CHIVA (Ambulatory Hemodynamic Cure of Venous Insufficiency) in case of major reflux, or association of the various technics. Thus, destructing treatments of saphenous veins should be only proposed to patients whose veins are obviously unsuitable for arterial bypass. PMID- 1861113 TI - [Venous endoscopy]. AB - The miniaturization of endoscopic equipment now allows exploring the superficial venous system and visualizing the endovein in situ and in vivo. This type of venous endoscopy is an ambulatory procedure, performed during a simple outpatient consultation of angiology, after which the patient is immediately discharged. Although this examination is invasive, non-physiological and expensive, it allows the video recording of the morphology, dynamics and kinetics of the values, of the endovein and of the liquid flows (blood, washing fluid and sclerosing products). The new examination has already enabled us to propose an functional classification of the parietal valves of the great saphenous vein. It makes an intraoperative three-dimensional mapping of the vessels possible, which is sometimes difficult in such particular anatomical regions as the popliteal fossa. It allows performing sclerosis with a visual control and following up the evolution of the immediate endoparietal lesions in situ. PMID- 1861114 TI - [Systemic scleroderma and thrombopenia. Demonstration of hepatic destruction of platelets]. PMID- 1861115 TI - [Percutaneous peripheral atherectomy with the Simpson catheter. Long term results]. PMID- 1861116 TI - [Treatment of deep venous thrombosis]. PMID- 1861117 TI - AAMC rips OMB's proposed cuts in Medicare GME payments. PMID- 1861118 TI - Medicare claims processing slowdown delays pay. PMID- 1861119 TI - How are octogenarians supposed to behave? PMID- 1861121 TI - Running from the reaper: the key to longer life. PMID- 1861120 TI - Augusta's resourceful Resource Center on Aging. PMID- 1861122 TI - The Old Medical College: a living monument to history and medicine. PMID- 1861123 TI - A freshman legislator's perspective on political action. PMID- 1861124 TI - The model medical marriage. PMID- 1861125 TI - Medicaid's new prescription drug legislation: prudent purchasing and drug use review. PMID- 1861126 TI - Cooperating with business rivals? From ski facilities to hospital joint ventures. PMID- 1861127 TI - Drug-induced agranulocytosis: experience in two university hospitals. AB - STUDY OBJECTIVE: to describe demographic data, offending drugs, clinical features, hematological profiles, clinical course, general outcome, factors influencing fatal result and microbiological aspects DESIGN: Retrospective descriptive analysis SETTING: Two university hospitals PATIENTS: 28 patients with 31 episodes of drug-induced agranulocytosis from Chulalongkorn Hospital (1976 1988) and 24 patients with 25 episodes from Songklanagarind Hospital (1983-1989) RESULTS: Female exceeds male by ratio of 2.1:1, age ranged 15-73 years. The common drugs were antimicrobial agents, penicillins and sulfonamides; antithyroid drugs; antituberculous drugs and non-steroidal antiinflammatory drugs (NSAIDs), unidentified in 16 per cent. About 61 per cent occurred more than 14 days after drug exposure. The key presentations revealed fever, prostration and sorethroat. Two marrow appearances were recognised: left-shifted granulopoiesis with few or no mature forms (type-I) in 66 per cent; and the other, selective reduction of granulocytic precursors (type-II). Penicillins, sulfonamides, antithyroid drugs and NSAIDs were all related to type-I. The leukocyte count, neutrophil and monocyte numbers were significantly higher in type-I, as well much more rapid recovery time (mean +/- SD, 4.4 +/- 1.5 vs 12.4 +/- 14.1 days, p = 0). The possible sites of infection were identified in 59 per cent, the major ones were oral cavity and GI tract. The organisms were isolated in 58 per cent from the primary sites and 25 per cent from hemocultures, of which Pseudomonas aeruginosa was the most common. The case fatality rate is 12.5 per cent. The dead victims had the higher age, and strongly association with type-II marrow appearance (p = 0.038). PMID- 1861128 TI - B vitamins status: effect of prolonged heroin addiction and methadone treatment. AB - Vitamin B1, B2 and B6 status were determined in 90 male heroin addicts admitted to Pramongkutklao Army Hospital. Their age (Mean +/- S.D.) was 25.5 +/- 7.8 years. Their activation coefficients of the enzyme transketolase, glutathione oxidoreductase and aspartate aminotransferase (ETK AC, EGR AC and EAST AC respectively) were significantly increased for addicts who were on drugs for a long time which indicated a biochemical deficiency. In addition, 26 follow-up cases treated with methadone for a period of one and two weeks were compared before and after treatment and it was found that ETK AC, EGR AC, and EAST AC were significantly decreased. This means that improvement in the vitamin B1, B2 and B6 status was obtained during admission. PMID- 1861129 TI - Chromosome analysis of 894 patients. AB - Metaphase chromosome analysis from cultured blood lymphocytes was performed in 894 consecutive patients from the year 1981 to early 1989. G-bands by trypsin using Giemsa (GTG) was routinely employed during the last five years supplemented with other banding techniques if required. High resolution chromosome banding was performed in cases suspected of structural chromosome abnormality. Successful studies were obtained in 862 (96.4%). Out of the successful cases, 232 (26.9%) had informative results, and 193 (22.4%) had chromosome abnormalities. Down's syndrome was found in 110 cases. Edwards' and Patau's syndromes were found in 4 and 7 cases respectively. A case of trisomy 14 mosaic was found. There were 2 cases of trisomy 22 syndrome, one case with 46,XX/47,XX,+mar(22) and another case with 46,XX/47,XX,+r(22) karyotype. There were 39 cases of sex chromosome abnormalities, 27 of which had Turner's syndrome. Kline-felter syndrome was found in 8 patients. Triple X syndrome and true hermaphrodite (46,XX/46,XY) was each found in one case. Autosomal deletions were found in 19 patients. Autosomal duplications were found in 4 patients, and autosomal translocations were found in 10 patients. Some of these autosomal structural abnormal cases have been included in the chromosomal syndromes mentioned above. PMID- 1861130 TI - A comparison of passive haemagglutination test and immunofluorescent test for antibody to native deoxyribonucleic acid. AB - Antibody to double-stranded DNA is a specific marker for systemic lupus erythematosus. The recommended method for detection of this antibody is immunofluorescence. Haemagglutination was developed and the results of antibody detection were evaluated with those obtained by immunofluorescence. Human group O erythrocytes were treated with glutaraldehyde and coated with DNA from calf thymus. Testing in 169 active and inactive SLE sera, 59 sera were positive and 91 sera were negative by both methods. Five sera were negative by haemagglutination but positive by immunofluorescence. Fourteen sera with low haemagglutination titer were negative by immunofluorescence. The correlation between the results obtained by both methods were highly significance with contingency coefficient of 0.61 and correlation coefficient between the results of 78 sera positive by both or either method was 0.74 (p less than 0.001). Sixty-three sera from blood donors and seventy sera from pregnant women were negative by the two techniques. PHA is simpler, quicker and can be assayed in laboratories without the use of fluorescent microscope. It can be established as a very useful alternative test to immunofluorescence. PMID- 1861131 TI - Leukocyte and neutrophil counts in differential diagnosis of acute febrile conditions. AB - Leukocyte and neutrophil counts are two of the commonest laboratory tests used in clinical medicine. The usefulness of the tests is still controversial. It has been found that the tests were useful to a limited extent. We performed leukocyte and neutrophil counts in patients manifesting acute febrile illness, to identify the best cut-off point in differential diagnosis of underlying disorders causing such conditions. Patients were enrolled randomly on the basis of acute febrile illness. Those who suffered from diseases affecting myeloproliferative system were excluded. Leukocyte and neutrophil counts were performed by the standard method. Diagnosis of target organ disorder was obtained from the house staff's final diagnosis. Both laboratory and clinical performance were assessed in double blind fashion. Patients were divided into 2 groups. Group 1 consisted of 47 patients with acute bacterial infections and group 2 consisted of 53 cases with acute febrile conditions caused by diverse, non-bacterial disease. Various cut off points ranging from 5,000-25,000/mm3 and 10-100 per cent were used for leukocyte and neutrophil counts. Sensitivity, specificity and Youden index for each cut off point were determined. Receiver operating characteristic (ROC) curves were constructed. It was found that sensitivity and specificity for each cut off point for both leukocyte and neutrophil counts displayed perfect trade offs and the Youden indices were similar. The ROC curves for both counts were depicted as a 45-degree lines of non-discrimination. Leukocyte and neutrophil counts were proved to be non-discriminate of acute febrile conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861132 TI - Pap smear examinations in women with near-term pregnancy. AB - Between November 28, 1983 and August 20, 1985 the Pap smears of 263 pregnant women at Siriraj Hospital were examined. They ranged in age from 15 to 40 years, with the mean age being 24.2 +/- 4.9 years. Pre-term pregnancies (24-37 weeks, 127 cases), at-term (38-42 weeks, 115 cases) and post-term (43-44 weeks, 21 cases) had inflammation and/or infection in 26.8, 40.0 and 23.8 per cent of each period, respectively; however, hormonal evaluation could not be carried out no matter what the period of pregnancy. More than half (60.6%) of the women with pre term pregnancy determined by history showed a pre-term cell pattern, 10.2 per cent at-term and 2.4 per cent post-term. Forty-two point six per cent of the women with at-term pregnancy determined by history showed the at-term cell pattern, 13.0 per cent showed the post-term pattern and 4.4 per cent the pre-term pattern; and 28.6 per cent of the women with post-term pregnancy determined by history showed the cell post-term pattern, 38.1 per cent the at-term pattern and 9.5 per cent the pre-term pattern. PMID- 1861133 TI - Causative organisms in puerperal infection. AB - Ninety-two postpartum women who had been admitted to Siriraj Hospital from April 1, 1980 to March 1, 1983 were studied for the causative organisms of puerperal infection. Cervical and intrauterine swab & smear-gram stain as well as cultures were performed. Hemocultures were done in some cases. Only 50 per cent of all cases had positive cervical and intrauterine swab smears which showed different kinds of micro-organisms, 78 per cent were gram-positive cocci, gram-negative rod was found in 4 specimens, 2 specimens of gonococcal smears, one for trichomonads. Cervical and intrauterine swab cultures were positive in only 31.5 per cent. E. Coli was the most common and Staphylococci & Streptococci were the second most common. PMID- 1861135 TI - Intracranial primitive neuroectodermal tumors: experience of 7 cases with particular reference to survival. AB - A group of neoplasms consisting of undifferentiated neuroepithelial cells being capable of differentiating into either neuronal or glial line or both directions has been termed "Primitive Neuroectodermal Tumors (PNETs)". They have been shown to possess several similarities in clinical, radiological, and pathological features to the cerebellar medulloblastomas. The latter are well treated by surgical removal followed by radiotherapy. Therefore, we used the same regimen in treating 7 patients with intracranial PNETs and obtained an average survival of 28.7 months which is longer than those of previous reports. The analysis of our patients disclosed an optimistic view that the ideal prognosis of PNETs should be better than this. PMID- 1861134 TI - Treatment of puerperal infection. AB - Ninety-two patients with puerperal infection admitted to Siriraj Hospital from April 1, 1980 to March 1, 1983 were studied. The treatment in this study was both medical and surgical, blood transfusion was given in some cases with low hematocrit level. The medical treatment alone was based on the causative organisms which were detected by cervical & intrauterine swab, smear & gram stain and cultures. PGS & Kanamycin were the most frequently used antibiotics which were intended to treat both gram-positive and gram-negative bacteria and adjunctive chloramphenicol for anaerobes. The surgical procedures which were performed in combination with medical treatment included total abdominal hysterectomy, uterine curettage, appendectomy and drainage of subdiaphragmatic abscess. The result of the treatment was satisfactory, 96.7 per cent improved after therapy with slight morbidity in some patients. PMID- 1861136 TI - Myotonia congenita, Klinefelter syndrome and primary hypoparathyroidism: the first report of the unusual combination of three rare diseases in the literature. AB - The first report of the rare combination of myotonia congenita, Klinefelter syndrome and primary hypoparathyroidism was reported. The patient was a 21-year old man who presented with stiffness of the muscles for 12 years and a history of generalised convulsion for 8 years. His school studies declined gradually and his secondary schooling was interrupted. Examination revealed a muscular young man with myotonic percussion over the muscles of the body as well as the myotonic lid lag. Chvostek's sign was positive and his serum calcium level was very low whereas the serum phosphate was high. Symmetrical and extensive calcification of the brain parenchyma was demonstrated in the CT scan. His secondary sexual characteristics were not well developed and his testes were very small. Chromosome study confirmed the diagnosis of Klinefelter syndrome by the identification of 47 XXY chromosome. He was prescribed calcium replacement and the anticonvulsant was withheld with no more episodes of seizure. PMID- 1861137 TI - Primary cardiac embryonal rhabdomyosarcoma: the first officially case reported of Thailand. AB - We reported the first case of a very rare tumor in Thailand, a case of cardiac Rhabdomyosarcoma. The first clinical presentation was cardiac tamponade. Echocardiogram, CT scan of the heart, autopsy and microscopic findings proved its origin. PMID- 1861138 TI - Recombinant human and rat ciliary neurotrophic factors. AB - The human ciliary neurotrophic factor (CNTF) gene was identified and cloned, based on homology with the recently cloned rat cDNA. The gene encodes a protein of 200 amino acids, which shares about 80% sequence identity with rat and rabbit CNTF and, like these homologues, lacks an apparent secretion signal sequence. The human CNTF gene, like the rat gene, appears to contain a single intron separating two protein coding exons. An intronless human CNTF gene was constructed by the use of polymerase chain reactions and introduced into vectors designed for expression of foreign proteins in E. coli. The rat CNTF gene was also introduced into similar vectors. Both the human and rat proteins were expressed at exceptionally high levels, at 20-40% and 60-70% of total protein, respectively. Extraction of the recombinant proteins from inclusion bodies by guanidinium chloride, followed by two column chromatography steps, produced high yields of pure CNTF that supported survival and neurite outgrowth from embryonic chick ciliary neurons in culture. The biological activity of both recombinant proteins was comparable to that of native rat CNTF. PMID- 1861139 TI - Characterization of delta-sleep-inducing peptide-evoked release of Met-enkephalin from brain synaptosomes in rats. AB - Delta-sleep-inducing peptide (DSIP) stimulates the release of Met-enkephalin (Met ENK) from superfused slices of the rodent lower brainstem in vitro. In our present study, DSIP (10(-10)-10(-9) M) induced a significant release of Met-ENK from medullary synaptosomes of rats. This DSIP-evoked release of Met-ENK was Ca2+ dependent and tetrodotoxin (TTX) insensitive. Furthermore, DSIP (10(-11)-10(-9) M) significantly increased 45Ca2+ uptake in medullary synaptosomes. These results demonstrate that DSIP acts directly on the nerve endings of Met-ENK-containing neurons to release this pentapeptide by generating a Ca2+ influx into these neurons. Effects of DSIP on Met-ENK release in other discrete brain regions were also studied. Significant DSIP-evoked Met-ENK release from synaptosomes was observed in the cortex, hypothalamus, and midbrain (at concentrations of 10(-10) and 10(-9) M) and in the hippocampus and thalamus (only at 10(-9) M), but not in the striatum. In the hypothalamus, the release of Leu-enkephalin from its synaptosomes was slightly, but not significantly, enhanced by DSIP (10(-10)-10( 8) M). Our findings demonstrate that DSIP triggered a Ca2+ influx in nerve endings to induce a subsequent release of Met-ENK from neurons in only certain brain regions. PMID- 1861140 TI - Splicing pattern of Gs alpha mRNA in human and rat brain. AB - Gs alpha, the GTP-binding protein that mediates receptor stimulation of adenylyl cyclase, exists in small (Gs alpha-S) and large (Gs alpha-L) molecular forms. Previous work has established that these Gs alpha isoforms are products of alternatively spliced Gs alpha pre-mRNA. The present work examined the splicing pattern of Gs alpha mRNA in rat and human brain using a method based upon the polymerase chain reaction. In rat brain, transcripts encoding Gs alpha-L were most abundant and constituted 92% of total Gs alpha mRNA in hippocampus and cerebral cortex and 84% in striatum. Compared to rat brain, the relative abundance of Gs alpha-L mRNA was less in human brain and constituted 84% of total Gs alpha mRNA in hippocampus and cortex and 66% in striatum. In addition, it was found that approximately 40% of the Gs alpha-S mRNA utilizes an alternative splice site that encodes serine at amino acid 72. No regional variations in this splicing pattern were found. PMID- 1861141 TI - Binding of botulinum and tetanus neurotoxins to ganglioside GT1b and derivatives thereof. AB - The ability of fragments derived from botulinum neurotoxin (BTx) serotype A to bind to GT1b-coated plastic wells was investigated and compared with the binding characteristics of the parent approximately 150-kDa protein. Although the approximately 50-kDa light chain of BTxA had a marginal binding capacity, the predominant adherence to GT1b-coated wells was exhibited by the approximately 50 kDa carboxy-terminal half of the approximately 100-kDa heavy chain of BTxA; the amino-terminal half of the heavy chain lacked the ability to bind. Binding to GT1b by BTxA and its fragments was compared with that of tetanus neurotoxin (TTx) and the carboxy-terminal half of its heavy chain. Binding of BTxA and the C terminal half of the heavy chain was optimal in buffers of low ionic strength (mu less than or equal to 0.04 and 0.06, respectively), whereas the heavy chain bound GT1b best at mu greater than or equal to 0.10. TTx and the approximately 50-kDa C terminal half of its approximately 100-kDa heavy chain bound GT1b at ionic strengths similar to those of BTxA. Comparison of the binding of BTx serotypes A, B, and E to GT1b (using conditions that were found to be optimal for binding by BTxA) indicated differences in the interaction of the three serotypes with GT1b. Compared with BTxA, adherence to GT1b by serotypes B and E was reduced by approximately 60 and approximately 90%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861142 TI - Biological and immunological properties of recombinant human, rat, and chicken nerve growth factors: a comparative study. AB - Biological and immunological properties of recombinant human, rat, and chicken nerve growth factors (NGFs) were studied and compared. Recombinant NGF proteins were produced in a transient expression system using COS cells and levels of secreted NGF protein were assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of conditioned media from in vivo [35S]cysteine-labeled cell cultures. Antigenic differences among the three NGFs were studied by immunoblotting and immunoprecipitation of secreted cell products using a rabbit polyclonal antiserum against purified mouse NGF, and by a two-site enzyme immunoassay (EIA) with a monoclonal antibody against mouse NGF. Although all three NGFs were recognized equally well in the immunoblotting, only one-third of the chicken NGF protein could be detected by immunoprecipitation or by the EIA as compared to the rat and human NGFs. Thus, changes in the three-dimensional structure of the NGF molecule are most likely responsible for the antigenic differences between avian and mammalian NGFs. The three NGF proteins were also compared in their ability to displace 125I-mouse NGF from low-affinity NGF receptors on rat pheochromocytoma PC12 cells. Similar displacement curves and values were obtained for each NGF protein, indicating that structural differences among these molecules do not affect low-affinity binding to NGF receptors. Biological activities were studied by the ability of the conditioned media to promote neurite outgrowth from explants of E9 chick sympathetic ganglia and from PC12 cells. Although the rat system showed a slight preference for the homologous molecule, the morphological changes, dose-response curves, and maximal stimulation values obtained with the different NGFs were practically indistinguishable in the chicken bioassay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861144 TI - Physicochemical characterization of recombinant human nerve growth factor produced in insect cells with a baculovirus vector. AB - Recombinant human nerve growth factor (rhNGF) secreted by insect cells was purified by ion-exchange and reversed-phase chromatography to near homogeneity. The N-terminus of the secreted molecule was analogous to that of mouse salivary gland NGF. In its native conformation, the insect cell produced rhNGF molecules were homodimers consisting of 120 amino acid polypeptide chains. Mature rhNGF was found not to be significantly glycosylated (less than 0.08 mol of N acetylglucosamine/mol of protein). The rhNGF was homogeneous with regard to molecular weight and amino acid sequence. Isoelectric focusing resolved the rhNGF into one major and one minor component. Because rhNGF from insect cells can be obtained in large quantities, purified to near homogeneity, and is similar to natural NGF with regard to physicochemical properties and biological activity, it is suitable for further evaluation in animal models as a therapeutic molecule for neurodegenerative diseases such as Alzheimer's disease. PMID- 1861143 TI - Depolarization and agonist-stimulated changes in inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate mass accumulation in rat cerebral cortex. AB - Muscarinic receptor stimulation or depolarization with elevated extracellular K+ induced rapid and sustained increases in mass accumulations of myo-inositol 1,4,5 trisphosphate [Ins(1,4,5)P3] and myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] in cerebral cortex slices. Synergistic but transient responses of both inositol polyphosphate second messengers were observed when slices were stimulated with carbachol under depolarizing conditions; this synergy was observed as an increase in the maximal responsiveness, with no significant change in EC50 values for carbachol. Omission of buffer Ca2+ ([Ca2+]e 10-20 microM) reduced basal Ins(1,4,5)P3 and Ins(1,3,4,5)P4 concentrations; the relative stimulatory effects of muscarinic receptor stimulation were maintained, but the effects of depolarization were markedly attenuated under these conditions. A component of the response to depolarization appeared to be indirectly mediated by the release of acetylcholine, because the K(+)-evoked increase in Ins(1,3,4,5)P4 was enhanced by the cholinesterase inhibitor physostigmine, and was partially attenuated by atropine. An additive suppression by nitrendipine suggests that entry of Ca2+ through L-type Ca2+ channels may serve to accelerate phosphorylation of Ins(1,4,5)P3 by 3-kinase. Norepinephrine did not significantly increase Ins(1,4,5)P3 or Ins(1,3,4,5)P4 accumulation; however, in the presence of depolarizing K+, norepinephrine caused a dramatic increase in Ins(1,3,4,5)P4 mass accumulation. In contrast, the excitatory amino acid quisqualate caused significant increases in the mass accumulations of both inositol polyphosphates measured, with no further increase being observed under depolarizing conditions. The results are discussed with respect to the interactive effects of agonist and depolarization stimuli on inositol polyphosphate accumulation which might more accurately reflect the conditions pertaining in vivo. PMID- 1861145 TI - Urinary but not brain isatin levels are reduced in germ-free rats. AB - Germ-free rats excreted considerably smaller amounts of the monoamine oxidase inhibiting compound isatin than the substantially larger output by conventional animals of the same strain, although concentrations in brain and other tissues were similar in the two groups. Thus, isatin is likely to be elaborated both endogenously in rat tissues and "exogenously" by flora inhabiting the lumen of the alimentary tract. PMID- 1861146 TI - Evidence for nonrandom distribution of GD1a ganglioside in rabbit brain microsomal membranes. AB - GD1a is the major ganglioside of rabbit brain microsomal membranes and occurs mainly with two molecular species, containing the C18:1 (62.3%) and C20:1 (37.7%) long-chain bases. The membranes were exposed to Vibrio cholerae (VC) sialidase under conditions where the enzyme hydrolyzed only GD1a (approximately 9%), producing GM1 ganglioside, whereas the other gangliosides remained virtually unaffected. The long-chain-base analysis showed that newly-formed GM1 contained approximately 68% of the C20:1 molecular species. This indicates that VC sialidase did not randomly affect the two molecular species of GD1a but hydrolyzed preferentially the C20:1 one. In similar experiments, GD1a was inserted into the external layer of phosphatidylcholine vesicles and incubated with VC sialidase under conditions producing approximately 10% hydrolysis. Long chain-base analysis showed that the proportion of C20:1 species in GM1 was 25.1% using vesicles composed of dipalmitoylphosphatidylcholine and 42.3% with egg phosphatidylcholine, whereas it was 39.2% in the starting GD1a. Therefore, in artificial membranes, VC sialidase acted preferentially on the C18:1 or C20:1 molecular species, depending on the length and unsaturation of the phospholipid fatty acids. Because VC sialidase is known to affect molecular dispersions more easily than packed aggregations of the gangliosidic substrate, the data suggest that in rabbit brain microsomal membranes the GD1a ganglioside molecular species carrying C20:1 long-chain base are more molecularly dispersed than those containing C18:1 long-chain base. PMID- 1861147 TI - Influence of bradykinin on diacylglycerol and phosphatidic acid accumulation in cultured bovine adrenal chromaffin cells. AB - Earlier studies have shown that bradykinin stimulated release of catecholamines from chromaffin cells by an influx of calcium through dihydropyridine-insensitive channels, and also that bradykinin stimulated (poly)phosphoinositide hydrolysis. To investigate membrane-bound second messengers in chromaffin cells, and to elucidate any role these may play in stimulus-secretion coupling, we have studied the influence of bradykinin on diacylglycerol and phosphatidic acid (PA). Using equilibrium labelling of primary cultures of chromaffin cells with [3H]arachidonic acid or [3H]glycerol, we found no influence of bradykinin (10 nM) on labelled diacylglycerol formation, either in the presence or absence of inhibitors of diacylglycerol lipase or kinase. However, when we used cells prelabelled with 32Pi for 2.5 h, we found that bradykinin produced a substantial stimulation of label found in PA, with an EC50 value of about 1 nM. This bradykinin stimulation of [32P]PA formation was only partially dependent on extracellular calcium, in contrast to the smaller response to nicotine, which was completely dependent on extracellular calcium. Short (10 min) pretreatment with tetradecanoylphorbol acetate (TPA) almost completely eliminated the bradykinin stimulated formation of inositol phosphates, but failed to affect bradykinin stimulation of label in PA, suggesting that PA production in response to bradykinin is not downstream of phospholipase C activation. TPA alone failed to stimulate [32P]PA substantially, whereas long-term (24 or 48 h) treatment with TPA failed to attenuate the response to bradykinin. Diacylglycerol kinase inhibitors were also without effect on the bradykinin stimulation of [32P]PA. These results suggest that bradykinin stimulates PA production by a mechanism independent of the activation of protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861148 TI - Phosphatidic acid accumulation and catecholamine release in adrenal chromaffin cells: stimulation by high potassium and by nicotine, and effect of a diacylglycerol kinase inhibitor R 59 022. AB - Using primary cultures of bovine adrenal chromaffin cells labelled with 32Pi, we show that stimulation with bradykinin, nicotine, or a depolarising concentration of potassium stimulates the accumulation of [32P]phosphatidic acid. The effects of nicotine and potassium are smaller than the effect of bradykinin, and are dependent entirely on extracellular calcium. The diacylglycerol kinase inhibitor R 59 022 attenuates the formation of phosphatidic acid by nicotine and depolarising concentrations of potassium. This inhibitor also blocks the nicotine and potassium stimulation of noradrenaline release from chromaffin cells. Using 45Ca2+ influx studies, we show that the nicotine-evoked calcium influx is also attenuated by R 59 022. These observations contrast with those in another report in which we showed that bradykinin stimulation of either [32P]phosphatidic acid accumulation or noradrenaline release is not affected by R 59 022. It is likely that the calcium influx produced by nicotine and depolarising potassium is blocked by R 59 022 by a mechanism that is independent of its ability to block diacylglycerol kinase. The nicotine- and potassium-stimulated [32P]phosphatidic acid accumulation is a consequence of this calcium influx and presumably reflects calcium activation of either phospholipase C or phospholipase D. PMID- 1861149 TI - The posttranslational processing of beta-endorphin in human hypothalamus. AB - beta-Endorphin is posttranslationally processed to six derivatives, which, although structurally similar, produce distinctly different biological effects. beta-Endorphin 1-31 is a potent opioid receptor agonist, but beta-endorphin 1-27 exhibits antagonist properties, and beta-endorphin 1-26 and the alpha-N-acetyl derivatives of all three peptides lack opioid receptor activity. In the present study, we identified the beta-endorphin peptides synthesized in human hypothalamus using cation exchange HPLC. First, we tested whether postmortem changes occur by storing rat hypothalami at 4 degrees C. This demonstrated that relative amounts of the six beta-endorphin forms did not change for up to 24 h, although total beta-endorphin immunoreactivity significantly declined after 6 h. HPLC analysis of human hypothalami revealed that beta-endorphin 1-31 was the principal form, constituting 58.4 +/- 5.4% of total immunoreactivity. Substantial amounts of beta-endorphin 1-27 (13.4 +/- 1.2%) and beta-endorphin 1-26 (13.1 +/- 1.6%) were also present, but alpha-N-acetylated forms were quantitatively minor, each comprising approximately 5% of total beta-endorphin. A similar processing pattern occurred in preoptic and suprachiasmatic areas of the hypothalamus. These results show that, despite differences in primary sequence, beta-endorphin is processed similarly in both rat and human hypothalamus. Opiate-active beta endorphin 1-31 is the principal form in both species. PMID- 1861150 TI - Characterization and partial purification of AIM: a plasma protein that induces rat cerebral type 2 astroglia from bipotential glial progenitors. AB - Studies on glial cultures have demonstrated that fetal bovine serum contains a factor that induces bipotential glial precursors known as oligodendrocyte-type 2 astrocyte (O-2A) progenitors to become type 2 astroglia rather than oligodendroglia. The goal of this research project was to characterize and purify this factor, which we refer to as the astroglia-inducing molecule (AIM). Using cultures enriched in O-2A progenitors, we determined that AIM is present in human and bovine sera and that fetal bovine serum qualified as the best serum for purifying AIM. AIM is heat and trypsin labile and may be a plasma glycoprotein. A 240-fold enriched AIM preparation was produced by applying an ammonium sulfate precipitate of fetal bovine serum to heparin and then lentil lectin-agarose, followed by gel filtration chromatography. In crude preparations, AIM activity migrated at 50 kDa by gel filtration. With enrichment, activity was seen at several molecular masses, all of which were approximate multiples of 50 kDa. Treatment with 6 M guanidine hydrochloride generated an AIM with a molecular mass between 12 and 18 kDa, a result suggesting that AIM aggregates. On a preparative isoelectric focusing gel, AIM activity most frequently migrated between pH values of 3 and 4; however, proteins with isoelectric points of greater than 9 or at 6 also had activity in several experiments. These data suggest that either multiple AIMs exist or that a single AIM exists that associates with other proteins. Immunofluorescence for ganglioside GD3 and glial fibrillary acidic protein confirmed that AIM preparations induce type 2 astroglia from O-2A progenitors and suggests that AIM has little effect on type 1 astroglia. Because none of the known growth factors that have been tested to date mimics its effects. AIM may be a novel differentiation factor. PMID- 1861151 TI - The mouse dopamine D2A receptor gene: sequence homology with the rat and human genes and expression of alternative transcripts. AB - To understand the possible involvement of dopamine receptors in the pathogenesis of various neurological disorders, we have cloned and sequenced a dopamine D2A receptor gene from the mouse. A mouse genomic library was screened with probes derived from the published sequence of a rat D2A receptor cDNA. Using restriction endonuclease mapping, Southern blotting, and DNA sequencing, we have determined the cDNA sequence and genomic organization of the mouse D2A receptor gene. Unlike other guanine nucleotide-binding protein-coupled receptors, but similar to its rat and human counterparts, the mouse D2A receptor gene has seven introns and spans at least 30 kb of genomic DNA. The mouse D2A sequence shows 99% amino acid homology with the rat and 95% amino acid homology with the human sequence. As would be predicted, sequence differences are significantly more frequent outside of the hypothesized transmembrane spanning domain regions of the protein. Using the polymerase chain reaction with primers made from neighboring exons, we have identified two alternatively spliced D2A transcripts in the mouse. However, in contrast to the other species studied, the mouse expresses primarily the mRNA representing the larger, 444-amino-acid form of the receptor. Mouse pituitary expresses only the mRNA of the 444-amino-acid form of the D2A receptor. Hence, the mouse may offer the best model to study the in vivo physiology of the long form of the D2A receptor. PMID- 1861152 TI - The differential role of protein kinase C isozymes in the rapid induction of neurofilament phosphorylation by nerve growth factor and phorbol esters in PC12 cells. AB - We examined the short-term regulation of the phosphorylation of the mid-sized neurofilament subunit (NF-M) by kinases which were activated in rat pheochromocytoma (PC12) cells by nerve growth factor (NGF) and/or 12-O tetradecanoylphorbol 13-acetate (TPA). We found that NGF and TPA, alone or in combination, increased (a) the incorporation of [32P]Pi into NF-M and (b) the rate of conversion of NF-M from a poorly phosphorylated to a more highly phosphorylated form. This was not due to increased synthesis of NF-M, because NGF alone did not increase NF-M synthesis and TPA alone or TPA and NGF together inhibited the synthesis of NF-M. Further, an increase in calcium/phospholipid dependent kinase (PKC) activity resulting from the treatment of PC12 cells with NGF and TPA was observed concomitant with the increased phosphorylation of NF-M. This PKC activity was determined to be derived from the PKC alpha and PKC beta isozymes. Finally, when PC12 cells were rendered PKC-deficient by treatment with 1 muM TPA for 24 h, NGF maintained the ability to induce an increase in NF-M phosphorylation, though not to the level attained in cells which were not PKC deficient. These data suggest that NGF with or without TPA stimulates NF-M phosphorylation as a result of a complex series of events which include PKC independent and PKC-dependent pathways. PMID- 1861154 TI - Comparative incorporation of proenkephalin-derived peptides, chromogranin A, and dopamine beta-hydroxylase into chromaffin vesicles. AB - The incorporation of enkephalin-containing peptides (ECPs) derived from proenkephalin into chromaffin vesicles was examined in primary cultures of adrenal medullary chromaffin cells. Cells were pulse-labeled with [35S]methionine and chased for periods up to 24 h. Chromaffin vesicles in cell homogenates were then fractionated by density gradient centrifugation and the presence of [35S]Met enkephalin sequences in gradient fractions determined. 35S-ECPs were incorporated into particles suggestive of immature vesicles within 1-2 h after radiolabeling. Vesicle maturation, measured by co-equilibration of 35S-ECPs and total ECPs in the gradients, was complete within 9-12 h and was unaffected by treatments that increase proenkephalin synthesis. Incorporation of [35S]chromogranin A into chromaffin vesicles followed a similar time course, but 35S-labeled dopamine beta hydroxylase was much more slowly incorporated, possibly reflecting differences in incorporation of membrane and soluble components. In summary, the data demonstrate that ECPs are rapidly sequestered in immature chromaffin vesicles, a process unaltered by changing rates of proenkephalin synthesis. PMID- 1861153 TI - Tumor necrosis factor-induced proliferation of astrocytes from mature brain is associated with down-regulation of glial fibrillary acidic protein mRNA. AB - Previous results from this laboratory have shown that tumor necrosis factor (TNF) is mitogenic for bovine astrocytes in chemically defined (CD) medium. The maximum mitogenic response was detected with 200 U/ml at 48 h. We have now extended these studies to assess the effect of TNF on message levels for the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin. The results have shown that, whereas TNF had only a slight effect on vimentin mRNA, TNF induced a marked decrease to 4.3 +/- 2.0% of controls in GFAP mRNA which was both time and dose dependent. The lowest effective dose was 50 U/ml and the maximal effective dose was 200 U/ml. Kinetic analysis of this response demonstrated that a marked decrease in GFAP mRNA was present at 12 h and continued to decrease through 72 h. To determine the reversibility of the TNF effect, astrocyte cultures were exposed to 200 U/ml TNF for varying periods of time and then cultured in fresh CD medium. A 1-h pulse with TNF was sufficient to reduce GFAP mRNA levels when measured 24 h later. However, cultures incubated with 200 U/ml TNF for 48 h followed by incubation in CD medium without TNF for 7 days showed that GFAP mRNA levels had returned to 60% of the control values. Nuclear runoff assays showed that the effect of TNF on GFAP mRNA was at the posttranscriptional level. Polyacrylamide gel electrophoretic analysis of astrocyte cytoskeletal proteins demonstrated that GFAP levels were reduced after a 5-day incubation with 200 U/ml TNF whereas protein levels of vimentin and actin were not significantly changed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861155 TI - Processing of proenkephalin in adrenal chromaffin cells. AB - The processing of proenkephalin was studied using [35S]methionine pulse-chase techniques in primary cultures of bovine adrenal medullary chromaffin cells. Following radiolabeling, proenkephalin-derived peptides were extracted from the cells and separated by reverse-phase HPLC. Fractions containing proenkephalin fragments were digested with trypsin and carboxypeptidase B to liberate Met enkephalin sequences and subjected to a second HPLC step to demonstrate association of radiolabel with Met-enkephalin. Processing of proenkephalin is complete within 2 h of synthesis, suggesting completion at or soon after incorporation into storage vesicles. Pretreatment of the cells with nicotine, histamine, or vasoactive intestinal peptide to enhance the rate of proenkephalin synthesis failed to alter the time course of processing and had minimal effects on the distribution of products formed. Addition of tetrabenazine, an inhibitor of catecholamine uptake into chromaffin vesicles, during radiolabeling and a 6-h chase period caused enhanced proenkephalin processing. These results suggest that the full range of proenkephalin fragments normally found in the adrenal medulla (up to 23.3 kDa) represents final processing products of the tissue and that termination of processing may depend on the co-storage of catecholamines. PMID- 1861157 TI - Stereospecificity of high- and low-affinity transport of choline analogues into rat cortical synaptosomes. AB - The present experiments used methylcholines to examine the stereoselectivity of choline transport into rat synaptosomes. R(+)-alpha-methylcholine and S(+)-beta methylcholine were significantly better inhibitors of the high-affinity choline transport system than were their enantiomers. Although both enantiomers of alpha- and of beta-methylcholine inhibited [3H]choline transport, only R(+)-alpha methylcholine and S(+)-beta-methylcholine could be transported by the high affinity choline uptake mechanism. Therefore, we conclude that the chiral requirements for recognition of and for transport by the high-affinity transporter are clearly different. In addition to high-affinity choline transport, Na(+)-independent low-affinity transport was measured. This process transported R(+)-alpha-methylcholine, but not S(-)-alpha-methylcholine; however, it showed no stereoselectivity for the enantiomers of beta-methylcholine. Thus, high- and low-affinity choline transport mechanisms exhibit distinct differences in their substrate selectivities. We suggest that the stereoselective properties of choline transport might present a unique opportunity to study choline uptake and metabolism. PMID- 1861159 TI - Saturable transport of manganese(II) across the rat blood-brain barrier. AB - Unanesthetized adult male rats were infused intravenously with solutions containing 54Mn (II) and one of six concentrations of stable Mn(II). The infusion was timed to produce a near constant [Mn] in plasma for up to 20 min. Plasma was collected serially and on termination of the experiment, samples of CSF, eight brain regions, and choroid plexus (CP) were obtained. Influx of Mn (JMn) was calculated from uptake of 54Mn into tissues and CSF at two different times. Plasma [Mn] was varied 1,000-fold (0.076-78 nmol/ml). Over this plasma concentration range, JMn increased 123 times into CP, 18-120 times into brain, and 706 times into CSF. CP and brain JMn values fit saturation kinetics with Km (nmol/ml) equal to 15 for CP and 0.7-2.1 for brain, and Vmax (10(-2) nmol.g-1.s 1) of 27 for CP and 0.025-0.054 for brain. Brain JMn except at cerebral cortex had a nonsaturable component. CSF JMn varied linearly with plasma [Mn]. These findings suggest that Mn transport into brain and CP is saturable, but transport into CSF is nonsaturable. PMID- 1861158 TI - Identification of serotonin receptors recognized by anti-idiotypic antibodies. AB - Anti-idiotypic antibodies were generated by immunizing rabbits with affinity purified antibodies to serotonin (5-hydroxytryptamine; 5-HT). Anti-5-HT activity was removed from the resulting antisera by chromatography through a 5-HT affinity column. The anti-idiotypic antibodies were demonstrated by enzyme-linked immunosorbent assay to bind to affinity-purified whole anti-5-HT antibodies and their Fab fragments. Anti-idiotypic antibodies, purified by affinity chromatography on columns to which antibodies to 5-HT were coupled, competed with 5-HT (covalently bound to protein) for the binding sites on anti-5-HT antibodies and serotonin binding protein. The anti-idiotypic antibodies antagonized the binding of [3H]5-HT to membranes isolated from the cerebral cortex, striatum, and raphe area more than to membranes from hippocampus or cerebellum. The anti idiotypic antibodies also blocked the binding of the 5-HT1B-selective ligand (-) [125I]iodocyanopindolol (in the presence of 30 microM isoproterenol) to cortical membranes. In contrast, anti-idiotypic antibodies failed to inhibit binding of the 5-HT1A-selective ligand 8-hydroxy-2-(di-n-[3H]propylamino)-tetralin [( 3H]8 OH-DPAT) to raphe area membranes or hippocampal membranes. These observations suggested that the anti-idiotypic antibodies may recognize some 5-HT receptor subtypes but not others. This hypothesis was tested by ascertaining the ability of anti-idiotypic antibodies to immunostain cells transfected in vitro with cDNA encoding the 5-HT1C or 5-HT2 receptor or with a genomic clone encoding the 5-HT1A receptor. Punctate sites of immunofluorescence were found on the surfaces of fibroblasts that expressed 5-HT1C and 5-HT2 receptors, but not on the surfaces of HeLa cells that expressed 5-HT1A receptors. Immunostaining of cells by the anti idiotypic antibodies was inhibited by appropriate pharmacological agents: immunostaining of cells expressing 5-HT1C receptors was blocked by mesulergine (but not ketanserin, 8-OH-DPAT, or spiperone), whereas that of cells expressing 5 HT2 receptors was blocked by ketanserin or spiperone (but not mesulergine or 8-OH DPAT). The anti-idiotypic antibodies failed to inhibit the uptake of [3H]5-HT by serotonergic neurons. It is concluded that the anti-idiotypic antibodies generated with anti-5-HT serum recognize the 5-HT1B, 5-HT1C, and 5-HT2 receptor subtypes; however, neither 5-HT1A receptors nor 5-HT uptake sites appear to react with these antibodies. PMID- 1861156 TI - Determination of acetylcholine release in the striatum of anesthetized rats using in vivo microdialysis and a radioimmunoassay. AB - A vertical-type in vivo microdialysis probe and a sensitive, specific radioimmunoassay (RIA) were used to study the mechanism of acetylcholine (ACh) release in the striatum of anesthetized rats. Without the use of physostigmine, a cholinesterase inhibitor, our RIA could still detect the amount of ACh present in the perfusate (5.6 +/- 0.6 fmol/min, n = 16). Tetrodotoxin (1 microM) produced a significant decrease in the amount of ACh collected in the perfusate, suggesting that basal ACh determined under the present experimental conditions was related to cholinergic neural activity. Atropine (0.1-1 microM) applied topically via the dialysis probe did not affect the amount of ACh recovered in the perfusate in the absence of physostigmine. Addition of physostigmine (10 microM) to the perfusion fluid produced about a 100-fold increase in the amount of ACh collected. In the presence of physostigmine, topical administration of atropine and pirenzepine (0.01-1 microM) through a dialysis probe produced a further three- to fourfold increase in ACh output, whereas a slight increase was produced by AF-DX 116 at the highest concentration (1 microM). These results indicate that presynaptic modulation of ACh release in the striatum does not occur under basal conditions, and that presynaptic M1 muscarinic receptors are involved in the modulation of ACh release when the ACh concentration is raised under certain conditions. PMID- 1861160 TI - K-252b is a selective and nontoxic inhibitor of nerve growth factor action on cultured brain neurons. AB - K-252b is a kinase inhibitor structurally related to K-252a, which is known to abolish selectively the effects of nerve growth factor (NGF) on PC12 cells and PNS neurons. We tested whether K-252b, K-252a, and staurosporine, another related compound, are effective and selective inhibitors of NGF actions on CNS neurons. All three compounds, at appropriate concentrations, completely and selectively prevented the NGF-mediated activity increase of the cholinergic marker enzyme choline acetyltransferase in cultures of rat basal forebrain cells. The stimulatory effects of basic fibroblast growth factor and insulin on choline acetyltransferase in these cultures and on dopamine uptake in cultures of dissociated ventral mesencephalon were not affected. No signs of toxicity were observed in cultures treated with K-252b. In contrast, K-252a and staurosporine, at concentrations required to block the NGF actions on cholinergic cells, were cytotoxic and produced cell loss. In addition, K-252a, at higher concentrations and in the absence of growth factors, increased cell numbers. Our study suggests that K-252b is a selective and nontoxic inhibitor of NGF actions in the brain and may become a useful tool to study these actions in vivo. PMID- 1861161 TI - Kininogen and kinin in experimental spinal cord injury. AB - Activation of the kallikrein-kinin system has been implicated in the pathogenesis of vasogenic brain edema and posttraumatic vascular injury. We determined the levels of kininogen and kinin in an experimental spinal cord injury model in the rat. Kininogen content in traumatized cord segments increased in a time-dependent manner. Western blot analysis showed that the kininogen in traumatized cord comigrates with 68K low-molecular-weight kininogen or T-kininogen. Trypsin treatment of the kininogen in traumatized cord released both bradykinin and T kinin, which were separated by HPLC and quantified with a kinin radioimmunoassay. Endogenous kinin levels in the frozen spinal cord also increased up to 40-fold 2 h after injury as compared with controls. The results demonstrate an increased accumulation of kininogen and its conversion to vasoactive kinins in experimental spinal cord injury. PMID- 1861162 TI - Nucleotide sequence and regulatory studies of VGF, a nervous system-specific mRNA that is rapidly and relatively selectively induced by nerve growth factor. AB - A nervous system-specific mRNA that is rapidly induced in PC12 cells to a greater extent by nerve growth factor (NGF) than by epidermal growth factor treatment has been cloned. The polypeptide deduced from the nucleic acid sequence of the NGF33.1 cDNA clone contains regions of amino acid sequence identity with that predicted by the cDNA clone VGF, and further analysis suggests that both NGF33.1 and VGF cDNA clones very likely correspond to the same mRNA (VGF). In this report both the nucleic acid sequence that corresponds to VGF mRNA and the polypeptide predicted by the NGF33.1 cDNA clone are presented. Genomic Southern analysis and database comparison did not detect additional sequences with high homology to the VGF gene. Induction of VGF mRNA by depolarization and phorbol 12-myristate 13 acetate treatment was greater than by serum stimulation or protein kinase A pathway activation. These studies suggest that VGF mRNA is induced to the greatest extent by NGF treatment and that VGF is one of the most rapidly regulated neuronal mRNAs identified in PC12 cells. PMID- 1861163 TI - Effects of hypoxia on the activity of the dopaminergic neuron system in the rat striatum as studied by in vivo brain microdialysis. AB - The purpose of the present study is to clarify the effects of hypoxia on the activity of the dopaminergic neurons in the brain and its mechanism of action. For this purpose, the effects of hypoxia on the extracellular levels of 3,4 dihydroxyphenylethylamine (dopamine) were examined in the rat striatum using in vivo brain microdialysis in the presence or absence of pretreatment with either tetrodotoxin (a blocker of voltage-dependent sodium channels) or nomifensine (a blocker of dopamine reuptake). Exposure to various degrees of hypoxia (15, 10, and 8% O2 in N2) increased dopamine levels in striatal dialysates to 200, 400, and 1,100%, respectively, of the control value. On reoxygenation, dopamine levels in the dialysates rapidly returned to the control level. Reexposure to hypoxia increased the dopamine levels to the same extent as during the first exposure. After addition of tetrodotoxin (40 microM) to the perfusion fluid or pretreatment with nomifensine (100 mg/kg, i.p.), exposure to hypoxia no longer increased the dopamine levels. These results suggest that although hypoxia induces an increase in the extracellular dopamine levels (hence, an apparent increase in the activity of the dopaminergic neurons), this increase is not the result of an increase in dopamine release itself, but rather the result of inhibition of the dopamine reuptake mechanism. PMID- 1861164 TI - Edward Garfield High (1919-1986). PMID- 1861165 TI - Obesity, a disorder of nutrient partitioning: the MONA LISA hypothesis. AB - The mechanisms underlying different types of obesity have been gradually clarified. Animal models with hypothalamic, genetic or dietary obesity have been examined with a feedback model. Four common final pathways are involved in this model. One of these final common pathways is the sympathetic nervous system. Most Obesities kNown Are Low In Sympathetic Activity states the MONA LISA Hypothesis. A second common pathway is the endocrine system involving adrenal glucocorticosteroids. The third common pathway is hyperphagia. Although not essential for most obesities, hyperphagia may be essential in animals with injury to the hypothalamic paraventricular nucleus. The final pathway is reduced physical activity. The tonic activity of these systems and their response to changes in the diet affect nutrient partitioning between fat and protein. This framework has been used to review genetic obesity, hypothalamic obesity and dietary obesity. PMID- 1861167 TI - Dietary taurine content and feline reproduction and outcome. AB - The reproductive performance and the outcome of the kittens was determined for female cats fed 0, 0.01, 0.02 or 0.05% taurine. Reproductive performance and outcome in the 0.02% group was substantially better than in the 0 and 0.01% groups but not as good as in the 0.05% group. Kittens in the 0.05% group had higher body weights and brain weights at birth and at 8 wk after birth than did kittens in the other groups. The concentration of taurine in milk was much higher in females fed 0.05% taurine (approximately 1.9 mmol/L) compared with females fed 0.02% taurine (approximately 0.55 mmol/L) or females fed 0 or 0.01% taurine (approximately 0.2 mmol/L). The concentration of taurine in tissues and fluids of adult females, newborn kittens and 8-wk-old kittens in the 0.05% group was significantly higher than in all other groups. In general, the concentration of taurine in tissues and fluids of the 0.02% group were not significantly different than in the 0 or 0.01% groups, with the exception of 8-wk-old kittens, in which several values, including retina and five brain regions, were significantly higher than in the 0 and 0.01% groups. These results indicate that the postnatal supply of taurine in the mother's milk had a greater impact than the intrauterine environment on the taurine concentration of the offspring in the 0.02% group; this amount of dietary taurine is still insufficient for a normal reproductive performance and resulted in significantly smaller taurine concentrations in adults and offspring. PMID- 1861166 TI - High dietary linoleic acid affects the fatty acid compositions of individual phospholipids from tissues of Atlantic salmon (Salmo salar): association with stress susceptibility and cardiac lesion. AB - For 16 wk Atlantic salmon (Salmo salar) post-smolts were fed practical-type diets that contained either fish oil (FO) or sunflower oil (SO) as the lipid component. Both diets contained adequate (n-3) polyunsaturated fatty acids (PUFA). All the phospholipids of heart and liver from SO-fed fish had increased levels of 18:2(n 6), 20:2(n-6) and 20:3(n-6); phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) also had increased 20:4(n-6). There was a general decrease in 20:5(n-3) in the phospholipids, reflected in an increase in the 20:4(n-6)/20:5(n 3) ratio, especially in PC and PE. The fatty acid compositions of phospholipids from brain and retina were much less affected by dietary linoleate than those of heart and liver. Fish fed SO developed severe heart lesions that caused thinning of the ventricular wall and muscle necrosis. The fish fed SO also were susceptible to a transportation-induced shock syndrome that caused 30% mortality. These results establish that a diet with a low (n-3)/(n-6) ratio can cause changes in fatty acid metabolism that are deleterious to the health of salmonid fish, especially when subjected to stress. PMID- 1861168 TI - Kinetics of rat peripheral nerve, forebrain and cerebellum alpha-tocopherol depletion: comparison with different organs. AB - Forty-two 60-d-old rats were fed a vitamin E-deficient diet for up to 8 wk and the kinetics of alpha-tocopherol depletion were measured in nervous tissue and various organs. In most tissues examined, including the sciatic nerve but not the cerebellum, the disappearance was biphasic, suggesting the existence of two pools of vitamin E. In forebrain the disappearance was poorly biphasic. After an 8-wk period of vitamin E deprivation, forebrain, cerebellum, sciatic nerve endoneurium, liver, heart, muscle, testes and serum vitamin E concentrations were 51, 64, 65, 10, 20, 20, 40, and 19%, respectively, of initial values. PMID- 1861169 TI - Effect of dietary deficiency and supplementation with all-rac-alpha-tocopherol on hepatic content in rats. AB - We studied the effect of dietary deficiency and supplementation with vitamin E in the form of all-rac-alpha-tocopherol in relation to the content of alpha tocopherol in parenchymal and nonparenchymal liver cells. The cells were isolated by centrifugal elutriation from rats fed diets containing normal, low or high amounts of vitamin E. The parenchymal cells contained about 90% of total hepatic alpha-tocopherol content in rats fed a nonpurified diet (reference group). However, the Kupffer and the endothelial/stellate cells contained four and two times more alpha-tocopherol, respectively, than the parenchymal cells per milligram of cell protein. When the rats were deprived of vitamin E for 8 wk, the content of alpha-tocopherol in parenchymal cells was reduced to 30% of values obtained from rats fed the nonpurified diet, and nonparenchymal cells contained very low levels of alpha-tocopherol (less than 5% of reference values). A diet enriched in vitamin E resulted in a sixfold increase in the content of alpha tocopherol in parenchymal cells but in small changes in nonparenchymal cells compared to the reference diet. Accordingly, the parenchymal cells may have storage capacity for alpha-tocopherol. The light mitochondrial and microsomal fractions contained high amounts of alpha-tocopherol. These fractions were subdivided by density gradient centrifugation to examine the alpha-tocopherol content in different cell organelles. The lysosomes and the Golgi apparatus were found to contain high levels of alpha-tocopherol, whereas peroxisomes contained small amounts. PMID- 1861170 TI - Phenytoin treatment and folate supplementation affect folate concentrations and methylation capacity in rats. AB - Phenytoin (PHT) has long been known to cause folate depletion with chronic use. In animal models PHT has been shown to interfere with folate-dependent one-carbon metabolism. Folic acid supplementation in humans has been shown to restore blood levels of folates to normal, but the effects of folic acid supplementation on the PHT-induced effects on one-carbon metabolism have not been addressed. In the present study rats were treated for 8 wk with 1) PHT, 2) folic acid, 3) PHT plus folic acid or 4) vehicle (propylene glycol). Phenytoin treatment caused a decrease in weight gain over the 8 wk of treatment. This effect on weight gain was reversed by folic acid supplementation, but the decrease in brain folate concentration caused by PHT was not reversed by folic acid supplementation, which by itself apparently caused a decrease in brain folate concentration. Phenytoin treatment tended to increase methylation capacity (S-adenosylmethionine:S adenosylhomocysteine ratio) in the brain and decrease methylation capacity in the liver. Folate supplementation by itself increased methylation capacity in the liver but had no effect in the brain. Folic acid and PHT apparently had independent but opposite effects in the liver, leading to a normalization of methylation capacity. These data suggest that folic acid supplementation in PHT therapy may be effective in reversing the peripheral effects of chronic PHT treatment on one-carbon metabolism but not the central effects. PMID- 1861171 TI - Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats. AB - Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (less than 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver, anemia, low plasma ceruloplasmin oxidase activity and increased 64Cu whole-body retention. Freshly isolated liver parenchymal cells from copper-deficient rats showed a higher 64Cu influx, which was associated with a higher apparent Vmax of 45 +/- 4 pmol Cu.mg protein-1.min-1 as compared with 30 +/- 3 pmol Cu.mg protein-1.min-1 for cells isolated from copper-sufficient rats. No significant difference in the apparent Km (approximately 30 mumol/L) was observed. Relative 64Cu efflux from cells from copper-deficient rats was significantly smaller than the efflux from cells from copper-sufficient rats after prelabeling as determined by 2-h efflux experiments. Analysis of the medium after efflux from cells from copper-deficient rats showed elevated protein-associated 64Cu, suggesting a higher incorporation of radioactive copper during metalloprotein synthesis. Effects of copper deficiency persist in primary cultures of parenchymal cells derived from copper deficient rats, and short-term cultures of these cells offer a prospect for the study of cell biological aspects of the metabolic adaptation of the liver to copper deficiency. PMID- 1861172 TI - Partial sequence of human plasma glutathione peroxidase and immunologic identification of milk glutathione peroxidase as the plasma enzyme. AB - Plasma glutathione peroxidase (p-GSHPx) is a unique selenoglycoprotein. A hepatic cell line synthesizes both this extracellular form for secretion and the cellular form that remains within the cells. Because the two forms could be a result of post-translational modifications of a product of a single gene, we partially sequenced p-GSHPx. Purified p-GSHPx was trypsin digested, and three of the peptides were sequenced. Only one of the peptide sequences was partially homologous to a sequence found in human cellular glutathione peroxidase. Because p-GSHPx is a secreted enzyme, we determined whether GSHPx in milk (another extracellular fluid) is due to this form of the enzyme. Ninety percent of human milk GSHPx activity could be precipitated by anti-p-GSHPx-immunoglobulin G. Thus, most, if not all, GSHPx activity in milk is due to the plasma selenoprotein form of the enzyme. In milk of two North American women, 3.6% and 14.3% of selenium was associated with GSHPx. PMID- 1861173 TI - Contribution of sulfate and sulfoesters to total sulfur intake in infants fed human milk. AB - Colostrum (d 2-4) and mature human milk samples (d 23-30) collected from eight mothers giving birth at 31 +/- 7 wk of gestation were analyzed for total sulfur, free inorganic sulfate and acid labile sulfoesters. The data presented are representative of complete 24-h expressions. Total sulfur was measured using a wet digestion procedure in which all forms of sulfur were converted to inorganic sulfate. The sulfate was quantified by a radiometric barium precipitation assay. Total sulfur showed no marked diurnal variation, but the mean concentration in 19 colostrum samples (10.2 +/- 4.2 mmol/L) was significantly higher than in 14 mature milk samples (4.3 +/- 0.8 mmol/L) (P less than 0.001). The range of predicted 24-h intakes of sulfur by infants fed colostrum (0.78-3.22 mmol/kg body weight) was slightly higher than those fed mature milk (0.54-1.06 mmol/kg), but it was not significantly different. The combined fractions of free inorganic sulfate and acid-labile sulfoester fractions contribute less than 5% to the total sulfur content of either colostrum or mature milk. However, the physiological significance of these milk components remains to be determined. PMID- 1861174 TI - Hepatic denervation alters the disposition of an enteral glucose load in conscious dogs. AB - The aim of this study was to establish the role of nerves to the liver in the disposal of an enteral glucose load. Dogs underwent a laparotomy during which the nerves to the liver were either left intact (C; n = 10) or removed (DN; n = 10). Absence of measurable liver norepinephrine was used to indicate completeness of denervation. Four weeks following surgery, 18-h fasted conscious dogs were given a glucose load (0.7 g/kg body weight) by gavage, and arterial blood samples were drawn over a 180-min period. The glucose and insulin excursions from baseline (incremental area) were 29% and 22% greater (P greater than 0.05) in DN than in C, respectively. Resting blood lactate levels were similar between groups, but they increased significantly more (P less than 0.05) following the administration of the glucose load in DN (peak change from resting level was 376 +/- 90 mumol/L in C and 728 +/- 81 mumol/L in DN). No significant differences between groups in glucagon, glycerol or alanine concentration were evident either prior to or following glucose administration. These data demonstrate that hepatic nerves can influence the substrate and hormone environment following an enteral glucose load. PMID- 1861176 TI - Comments on some changes in plasma cholesterol and vitamin E when different fats are fed. PMID- 1861175 TI - Dietary arginine supplementation does not enhance lymphocyte proliferation or interleukin-2 production in young and aged rats. AB - Recent studies indicate that supplemental arginine may enhance in vitro lymphocyte mitogenesis. To determine whether dietary arginine could reverse age associated losses in immune functions, we fed purified amino acid diets to young (2-mo-old) and aged (24-mo-old) Fischer 344 rats. Rats receiving control (1.12% arginine) or supplemented (3% arginine) diets were pair fed to intakes of deficient (0% arginine) rats. Another group was fed the supplemented diet ad libitum. On d 15, responses of splenocytes to phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) were lower (P less than 0.01), but interleukin-2 (IL-2) production was higher (P less than 0.05) in aged rats than in young rats. At mitogen doses producing maximal stimulation, supplemental arginine did not enhance PHA-, Con A- or PWM-stimulated lymphocyte proliferation; PWM responses at sub-maximal doses were higher in pair-fed supplemented rats than in control or ad libitum supplemented rats (P less than 0.05). Arginine supplements did not increase thymus weights or IL-2 production above controls. In another experiment, weanling rats received control and supplemented diets in amounts equal to the intake of deficient rats for an average of 37 d. Splenocytes were cultured with mitogens at various arginine levels. No diet effect was observed. Mitogenesis was maximal when media arginine approximated normal plasma levels. Our results suggest that supplemental arginine has little effect on lymphocyte proliferation or IL-2 production in healthy young and aged rats. PMID- 1861177 TI - The inventive genius of an Oklahoma dentist. PMID- 1861178 TI - The emerging profile of dental manpower in Oklahoma. 2. Tulsa county. AB - This is the second report of a three part study. Part I focused upon the dental manpower profile of Oklahoma County between the years 1972-1989. Part II emphasizes the dental manpower profile of Tulsa County. Part III, will be inclusive of the dental manpower profile of all other Oklahoma counties. In all phases of the study, data has been assessed for general practitioners, specialists, full-time general practice dental faculty, full-time specialist dental faculty, and public health dentists. The demographic data analyzed in Part I, revealed an increasing average of the dentists from 45.33 years of age in 1972 advancing to 48.83 years of age in 1989 for Oklahoma County. The data presented in Part II documents that in Tulsa County there was an increase in age from 45.68 in 1972 to 50.60 in 1989. Trends in location of dental school education, demonstrated that the University of Oklahoma College of Dentistry is currently the primary resource for the dental manpower pool in Tulsa and Oklahoma Counties. Changes in the dental manpower pool indicate a downward turn in the percentage of dentists choosing to locate in either Tulsa or Oklahoma County. PMID- 1861179 TI - Effects of pin head configuration on the strength of a palladium-enriched high copper dental amalgam. PMID- 1861180 TI - National Practitioner Data Bank: good idea ... bad result. PMID- 1861181 TI - Dysphagia and the elderly: an emerging challenge for dentistry. PMID- 1861182 TI - Surviving hard times in your practice. PMID- 1861183 TI - Generalist and specialist: the referral process. PMID- 1861184 TI - Insurance management. PMID- 1861185 TI - The effect of concomitant chondral injuries accompanying operatively reduced malleolar fractures. AB - The best clinical results in the treatment of malleolar fractures occur when an anatomic reduction is obtained and maintained until the fractures are healed. Ankle pain and/or tibio-talar arthrosis has been reported despite anatomic surgical reduction and stable fixation of the malleoli. This may be due to unrecognized injuries to the cartilaginous surfaces of the tibio-talar joint. Between 1984 and 1987, 63 patients with isolated closed malleolar fractures underwent open reduction and internal fixation using standard AO techniques. Each patient had inspection of the entire talar dome during surgery. There were seven type A, 37 type B, and 19 type C fractures. Thirty-one patients (49%) had injuries to the talar dome cartilage, ranging from mild scuffing to free osteochondral fragments. Twenty-five patients were available for a follow-up evaluation at an average of 25 months after surgery. Thirteen patients had some complaints of pain, eight of whom had talar dome chondral injuries. The overall results, including functional status and ankle range of motion, were significantly poorer in patients with talar dome chondral injuries (p less than or equal to 0.03 and p less than or equal to 0.042, respectively). PMID- 1861186 TI - Proximal humeral osteotomy to correct the anatomy in patients with recurrent shoulder dislocations. AB - Surgical treatment of patients with traumatic shoulder dislocations is usually successful, but soft-tissue surgery in patients with nontraumatic shoulder dislocation often fails to stabilize the joint. Previous studies have shown that decreased humeral head retroversion might be one cause of anterior shoulder instability. Eleven patients with anterior recurrent dislocations, five traumatic and six nontraumatic, and all with a small humeral head retroversion angle, have been operated on using a proximal humerus osteotomy to correct the abnormal anatomy. After surgery, the humeral head retroversion was normalized to a mean angle of 34 degrees. All shoulders became stable. External rotation increased 7 degrees on the average, and internal rotation decreased 10 degrees on the average. One year after surgery, shoulder function was excellent in all operated shoulders. PMID- 1861187 TI - Compartment syndrome after low-velocity gunshot wounds to the forearm. AB - Between 1980 and 1988, 127 patients with 131 low-velocity gunshot wounds to the forearm were treated. In 71 extremities there was no bony injury; 60 extremities sustained fractures. The diagnosis of a compartment syndrome was based on tissue pressure measurements and/or clinical examination. A univariate analysis followed by a multivariate stepwise logistic regression was used to evaluate potential risk factors including fracture location, displacement, comminution, and the quantity of radiographically determined metallic foreign bodies in the wound. A compartment syndrome was diagnosed in 13 of the extremities (10%). Fracture location was the only significant risk factor for the development of a compartment syndrome. Low-velocity gunshot injuries to the forearm are at definite risk for the occurrence of a compartment syndrome. A high index of suspicion is necessary to prevent untoward sequelae. Patients with this injury, especially those with a proximal one-third fracture who constitute an extremely high-risk group, should be monitored closely. PMID- 1861188 TI - Mechanical and biological effects of plate luting. AB - Plate luting, a technique that uses polymethylmethacrylate (PMMA) interposed between the plate and the bone, as well as between the screw heads and the plate, to improve the stability of internal fixation was tested in vitro using 20 paired equine third metacarpal bones with mid-diaphyseal osteotomies plated with six hole broad ASIF compression plates. One of each pair was luted and all specimens were tested in static overload or cyclic loading at 75% of the ultimate breaking strength using four-point bending. Although no differences were measured in static overload tests between luted and nonluted plates, a three to 12-fold increase in the number of cycles to failure was noted with the luted specimens. In vivo studies of the biological reaction to plate luting were performed in seven horses using identical plates fixed to the intact radius. One side was luted while the opposite side was plated without luting. The horses were killed at 1, 2, 6, and 15 months after surgery. Quantitative histomorphometry showed no increase in porosity under the luted plate when compared with the nonluted side. PMID- 1861189 TI - External minifixation for treatment of closed fractures of the metacarpal bones. AB - External minifixators were used in the treatment of 63 closed diaphyseal metacarpal bone fractures. A simple half-frame configuration was applied in all the cases. Open reduction was performed in 26%. The mean duration of external fixation was 30 days. There were no cases of nonunion. Anatomical reduction was obtained in 86.6% of the cases. There were no cases of reflex sympathetic dystrophy. The general functional results were very good or good in 96.6%. Open reduction did not significantly alter the final results. External minifixation is usually accepted as a treatment of open metacarpal fractures. Because of the excellent results obtained in our series, we believe that the indications of external minifixation could be enlarged to closed metacarpal bone fractures. PMID- 1861190 TI - Flexion distraction and chance injuries to the thoracolumbar spine. AB - Seat belt legislation has resulted in increased restraint use by passengers in automobiles in Washington State. At Harborview Medical Center in Seattle, we have observed an increased incidence of seat belt-related injuries. Twenty cases of Chance-type thoracolumbar flexion-distraction fractures were reviewed retrospectively. Thirteen patients (65%) had associated life-threatening intra abdominal trauma. Twelve of these patients had bowel wall injury. Ninety percent of the children had combined abdominal and spinal injury. Operative treatment of the spinal injury resulted in correction of lumbar kyphosis and lower incidence of back pain than nonoperatively managed cases. We recommend careful physical and radiographic examination of all patients with significant abrasion or bruising about the pelvis or abdomen related to seat belts. Victims of automobile crashes who are treated for bowel injury require thoracolumbar radiographs. Similarly, patients with Chance-type fractures should undergo diagnostic peritoneal lavage or computerized abdominal tomography. PMID- 1861191 TI - Somatosensory evoked potential monitoring in the surgical management of acute acetabular fractures. AB - Fifty patients undergoing acute acetabular fracture surgery had intraoperative somatosensory evoked potential (SSEP) monitoring. Group II, the final 38 patients, in addition had independent neurological evaluation preoperatively and postoperatively. Thirteen of 50 patients (26%) had preoperative sciatic nerve involvement. Fourteen of 50 patients (28%) developed significant intraoperative SSEP changes (decreased amplitude, increased latency). When the nerve was involved preoperatively (high-risk group), changes in SSEP occurred in 60% of patients. Iatrogenic sciatic/peroneal neuropraxia occurred in only one patient in the series (2%), and this resolved within 4 months. These results compare favorably to the incidence of 5-18% reported in the literature. We conclude SSEP is feasible and should be used in the operative treatment of acetabular fractures, especially the posterior fracture patterns and for those in the high risk group. PMID- 1861192 TI - Posterior acetabular wall fractures: a technique for screw placement. AB - Screw placement at the posterior margin of the acetabulum during open reduction and internal fixation of posterior acetabular wall fractures must avoid intraarticular penetration of the hip joint. Analysis of the preoperative computed tomography (CT) scan, operative positioning of the patient in a secure reference plane, and placement of the screws in the coronal plane perpendicular to the long axis of the body will help avoid this surgical complication. PMID- 1861193 TI - Results of surgical repair versus splinting of experimentally transected muscle. AB - Complete muscle tears or transections can be treated by splinting or surgical repair. Although repair is often advocated in the young and athletic population, no well-controlled studies compare the results of splinting and surgical repair. I studied the effects of surgical repair versus splinting only of transected muscles in an experimental model. In group I (n = 14), a unilateral transection of the extensor digitorum longus (EDL) muscle of the Sprague-Dawley rat was treated with splinting only. In group II (n = 14), the muscle was surgically repaired as well. Active and passive strength measurements at day 7 and 14 showed an earlier return of passive strength in group II at day 7. No statistically significant differences at day 14 were noted. In this model, earlier return of active and passive strength occurred in surgically repaired muscle disruption as compared with nonrepaired muscles. PMID- 1861194 TI - Treatment of ipsilateral fractures of the distal femur and femoral shaft. AB - Thirteen patients with segmental fractures involving the distal femur and femoral shaft were treated with internal fixation. Nine of the distal femur fractures were intraarticular. Priority was given to restoration of the articular surface and the alignment of the distal femur. No single method of fixation could be used for all patients. Nine patients were treated using plate fixation with one or more plates. Three patients were treated with a combination of an interlocked intramedullary nail and lag screw fixation. One patient was treated with Ender nails. All the fractures eventually healed, but the recovery time was long. Although no patient was asymptomatic, 10 have resumed their preinjury level of function. PMID- 1861195 TI - Ankle mortise stability in Weber C fractures: indications for syndesmotic fixation. AB - A Weber type C ankle fracture was sequentially reproduced in 12 cadaver lower extremities and an external rotation torque was applied at each interval. The fractures were then repaired in staged fashion and the rotational stability of the mortise evaluated. Maximum external rotation of the talus within the mortise averaged 7.7 degrees in the intact ankle and increased by 311% to 31.8 degrees after creation of a Weber C injury. Rigid fixation of the fibular fracture restored 32% of the rotational stability, whereas isolated fixation of the medial malleolus reconstituted 57%. Fibular fixation combined with a syndesmotic screw restored 51% of original stability, and the addition of medial malleolar fixation improved stability to 101%. Bimalleolar fixation without a syndesmotic screw yielded 73% of the original rotational stability. The results of this study suggest that when rigid medial and lateral osteosynthesis can be achieved, syndesmotic fixation may not be necessary. PMID- 1861196 TI - Anatomic considerations in posterior plating of the cervical spine. AB - We evaluated the anatomic structures at risk during posterior plating of the cervical spine and outlined a safe technique for screw insertion. Three cadaveric specimens were evaluated anatomically and radiographically. Screws and wires were inserted into the articular masses at different locations and angulations. The relationship of the neurovascular structures to the screws and wires was noted. To avoid injury to the nerve roots, vertebral artery, and spinal cord, the screw should be placed in the center of the articular masses perpendicular to the vertebral plane with 15 degrees lateral angulation. PMID- 1861197 TI - An unusual type of fracture in the upper sacrum. AB - An unusual type of indirect isolated fracture of the upper sacrum is presented. The upper sacrum was markedly comminuted and nondisplaced relative to the lower fragment. There was a neurologic deficit present. On the basis of a review of the literature, a previous classification system and the actual fracture mechanism, this fracture is classified as a special type; type 4, or the neutral position fracture. PMID- 1861198 TI - Shark attack. AB - Shark attacks are rare but devastating. This case had major injuries that included an open femoral fracture, massive hemorrhage, sciatic nerve laceration, and significant skin and muscle damage. The patient required 15 operative procedures, extensive physical therapy, and orthotic assistance. A review of the literature pertaining to shark bites is included. PMID- 1861199 TI - Nonunion of a complex tibial plateau fracture. AB - Nonunion of tibial plateau fractures are uncommon; only five cases have been reported in the literature. This report presents the sixth nonunion and highlights the management of an angulated, periarticular pseudoarthrosis. Pitfalls in the initial fracture treatment that contributed to the development of the pseudoarthrosis are reviewed. PMID- 1861200 TI - A prospective randomized trial of external fixation and plaster cast immobilization in the treatment of distal radius fractures. PMID- 1861201 TI - Cerebral Doppler studies in the fetus and newborn infant. AB - The goal of developing reliable commercial Doppler systems for measuring vessel diameter and velocity changes during the cardiac cycle appears to be near. Reaching this goal would enable us to obtain volume-flow information continuously. In animal experiments, continuous measurements of Doppler velocity, pressure, and flow add important insights into hemodynamic measurements. Incorporating Doppler methods in microcirculatory research could also provide a link between the microcirculatory and the macrocirculatory hemodynamic research. Although Doppler methods have been validated, Doppler findings in clinical research (using commercial systems) must be considered at best to reflect qualitative circulatory alterations indicating directions of change. Because of inherent technologic limitations and considerable intersubject and intrasubject variability, direct extrapolation of the numeric findings from one study to the other can lead to misleading conclusions. The Doppler results are also influenced by measurement conditions and equipment settings. However, Doppler-derived information can be used as an adjunct to clinical management in many of the diseases discussed above. As with any physiologic variable, serial measurements probably are of greater value than single measurements. With continued improvement in technology, Doppler methods hold promise of becoming an important adjunct in cerebral hemodynamic monitoring in perinatal-neonatal intensive care units. PMID- 1861202 TI - Graduate medical education during the fourth year of medical school. PMID- 1861203 TI - Blood glucose control and albuminuria in type 1 diabetes mellitus. AB - The relationship between long-term blood glucose control and albuminuria in type 1 diabetes was investigated in 42 male and 58 female patients who had had diabetes mellitus for more than 7 years. Their mean (+/- SD) age and diabetes duration were 18.6 +/- 3.6 and 12.1 +/- 3.5 years, respectively. For periods of observation ranging from 1 to 6 years (mean 4.4 +/- 1.5), hemoglobin A1c (HbA1c) was measured two to six times yearly (mean of 8.8 +/- 3.9 determinations per patient). Albumin excretion rate (AER) was measured in single-void urine samples two to four times in 93 patients and once in the other seven patients. The 52 patients with mean HbA1c no more than 9.0% had significantly lower mean AER than those whose HbA1c was greater than 9.0% (20.1 +/- 24.6 vs 265 +/- 1005 mg/gm Cr, p less than 0.001). Only five (9.6%) of these 52 patients had elevated AER values (greater than 40 mg/gm Cr), whereas 21 (43.7%) of 48 patients whose mean HbA1c was greater than 9.0% had elevated AER values (p less than 0.001). Six male but no female patients had mean AER values greater than 300 mg/gm Cr. The 74 patients with normal AER had significantly lower mean HbA1c values than the 26 with elevated AER (8.6 +/- 1.5 vs 10.1 +/- 1.6%, p less than 0.001). These results support the contention that maintenance of HbA1c levels at no more than 9% (one and one-half times the upper limit of normal) will significantly decrease the likelihood that diabetic nephropathy will develop. PMID- 1861204 TI - Nosocomial measles infection in a pediatric hospital during a community-wide epidemic. AB - From Jan. 1, 1988, through Dec. 31, 1988, a total of 89 cases of measles were observed at Childrens Hospital of Los Angeles, and 37 patients were admitted to the hospital. Of the 37 patients, six were not initially thought to have measles, which resulted in exposure of 107 patients and 24 personnel. Of the exposed patients, measles developed in four. One nosocomially infected infant died of pneumonia. Another exposed patient was subsequently admitted to another hospital with unrecognized measles, which led to exposure of an additional eight patients. Of seven employees in whom measles developed, two required hospitalization because of pneumonia. Two hundred eleven employee days were lost because of measles exposure or infection. Infection control interventions included prophylaxis of exposed patients, employee education, and measles immunization for susceptible personnel. Of 1103 hospital personnel considered susceptible to measles, 800 received monovalent measles vaccine. No secondary cases of measles occurred in hospital personnel who received appropriate prophylaxis. We conclude that infection control programs aimed at mandating measles immunity in hospital employees at risk should be instituted. PMID- 1861205 TI - Mumps outbreak in a highly vaccinated population. AB - From October 1988 to April 1989, a large mumps outbreak occurred in Douglas County, Kansas. Of the 269 cases, 208 (77.3%) occurred among primary and secondary school students, of whom 203 (97.6%) had documentation of mumps vaccination. Attack rates were highest for students attending junior high school (8.0%), followed by high school (2.0%) and elementary school (0.7%). A retrospective cohort study conducted at one junior high school with an attack rate of 12.9% did not find age at vaccination or type of vaccine received (single or combined antigen) to be risk factors for vaccine failure. Students vaccinated more than 4 years before the outbreak appeared to have a higher attack rate than those vaccinated more recently (relative risk (RR) = 4.3; 95% confidence interval (CI) = 0.6, 30.0); however, this association did not exist when risk was evaluated based on number of vaccine doses received. Students who had documentation of receiving only one dose of vaccine were at greater risk than those who had received two doses (RR = 5.2; 95% CI = 1.0, 206.2). Overall, vaccine effectiveness among Douglas County junior high school students was estimated to be 83% (95% CI = 57%, 94%). These data suggest that mumps vaccine failure and the failure to vaccinate have contributed to the relative resurgence of mumps observed in the United States since 1986. The recent change in immunization policy to recommend a two-dose schedule of measles-mumps-rubella vaccine should help reduce the occurrence of mumps outbreaks in highly vaccinated populations. PMID- 1861206 TI - Serum immune response to Helicobacter pylori in children: epidemiologic and clinical applications. AB - Antibody responses to Helicobacter pylori were measured by a solid-phase whole cell enzyme-linked immunosorbent assay in 150 children and adolescents; in 47 consecutive children undergoing upper gastrointestinal endoscopy, including 17 with H. pylori infection before and after antimicrobial treatment; and in 46 family members of the infected children. Abnormal levels of either IgG or IgA were found in 6% of the 150 children. In the latter group the prevalence of H. pylori seropositivity increased with age. Parents and siblings of the infected children had 94% and 71% seropositivity, respectively, suggesting intrafamilial spread. Abnormal levels of IgG or IgA against H. pylori identified infected children with 95% sensitivity and 84% specificity. Eradication of the infection was accompanied by a significant decrease in IgG and IgA titers, with normalization in 10 cured patients in 12 months or less. We conclude that the method described for evaluation of H. pylori-specific IgG and IgA antibodies gives helpful information on the epidemiology of the infection and represents a useful adjunct to diagnosis and management of chronic gastritis in children. PMID- 1861207 TI - Epidemiology of hemolytic-uremic syndrome in Canadian children from 1986 to 1988. The Canadian Pediatric Kidney Disease Reference Centre. AB - OBJECTIVE: To define the epidemiologic features of childhood hemolytic-uremic syndrome (HUS) on a national level in Canada, to determine the proportion of patients in whom Escherichia coli O157:H7 was isolated from stools, and to examine risk factors for more severe HUS. DESIGN: From January 1986 to December 1988, patients with HUS were reported prospectively to the Canadian Pediatric Kidney Disease Reference Centre, a national registry for pediatric renal disorders, or were identified retrospectively through a medical records search at participating institutions. SETTING: All children's hospitals in Canada and the children's wards of general hospitals in Canadian cities with populations greater than 350,000. PATIENTS: Two hundred twenty-six children, including 126 girls. MEASUREMENTS AND MAIN RESULTS: The average annual incidence of HUS in children younger than 15 years was 1.44 per 100,000; the peak age-specific incidence was 3.11 per 100,000 younger than 5 years. The incidence of HUS varied by region; the risk of HUS in Alberta was 2.9 times that in Ontario (p less than 0.0001). Of the 169 patients whose stools were screened, E. coli O157:H7 was isolated in 87 (51%). Risk factors for prolonged dialysis or death included young age, seizures, elevated white blood cell count at admission to hospital, and shorter, more severe prodromal illness. The rate of dialysis was higher in female patients (55% vs 39%; p = 0.02). CONCLUSIONS: HUS is relatively common in Canadian children younger than 5 years, and is strongly associated with E. coli O157:H7 infection. Reasons for the striking regional variation in the incidence of HUS and for the increased rate of dialysis in female patients are unexplained and deserve further investigation. PMID- 1861208 TI - Mass screening in Japan increased the detection of infants with neuroblastoma without a decrease in cases in older children. AB - Analysis of data from the Kanto-Ko-Shin-Etsu Branch of the Japan Children's Cancer Registry revealed that mass screening for neuroblastoma increased the detection of cases in infants younger than 1 year from about 25% before screening to about 50%, and the percentage of neuroblastomas among all pediatric cancers almost doubled, from approximately 10% to 19.3%. However, when the cases found on screening were subtracted, the numbers after the onset of mass screening were similar to those before screening. It is likely that neuroblastoma mass screening has identified a unique type of tumor, which may not be recognized without mass screening, rather than that it has contributed to the earlier diagnosis of tumors in older children. PMID- 1861209 TI - Mitochondrial encephalomyopathies in childhood. I. Biochemical and morphologic investigations. AB - During a 4-year period (1984 to 1988), 50 children referred with manifestations of central nervous system or neuromuscular disease combined with hyperlactatemia were subjected to investigations that aimed to identify and characterize children with mitochondrial disorders. Biochemical and morphologic investigations of quadriceps muscle biopsy tissue were done, including oximetric and spectrophotometric analysis of the respiratory chain function, enzyme histochemistry, electron microscopy, and analysis of mitochondrial DNA. A diagnosis of mitochondrial disease was based on the presence of at least two of five criteria: (1) abnormal results of oximetry, (2) abnormal results of spectrophotometry, (3) enzyme histochemical evidence of cytochrome x oxidase deficiency, (4) deletions or point mutations of mitochondrial DNA, and (5) abundant ultrastructurally abnormal mitochondria. With the combined biochemical and morphologic investigation, 20 of the children were found to have mitochondrial disorders. In an additional 10 children a mitochondrial disorder was neither excluded nor verified. Mitochondrial disorders are thus an important cause of central nervous system and neuromuscular disease in children with hyperlactatemia. PMID- 1861210 TI - Mitochondrial encephalomyopathies in childhood. II. Clinical manifestations and syndromes. AB - During a 4-year period 1984 to 1988, 20 children referred with manifestations of central nervous system or neuromuscular disease combined with hyperlactatemia were found to have a mitochondrial disease. Each diagnosis was based on the results of thorough biochemical and morphologic investigations. The patients were separated into one series with mainly encephalopathy (n = 14) and another with mainly myopathy (n = 6). The patients with encephalopathy had the following syndromes: Kearns-Sayre (n = 2), MERRF (myoclonus epilepsy and ragged red fibers; n = 2), MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes; n = 3), Alpers (n = 3), Leigh (n = 1), and other variants (n = 3). In patients with myopathy, three had hypertrophic nonobstructive cardiomyopathy. Ultrastructural abnormalities of mitochondria were the most common morphologic changes in the muscle biopsies. Complex I deficiency was most common in the patients with encephalopathy. All of the patients with myopathy had complex IV deficiency. Mutations of mitochondrial DNA were found in six patients with encephalopathy. We conclude that identification of defects at the DNA level and determination of the phenotypic expression with clinical, morphologic, and biochemical methods are fundamental for future rational classification of mitochondrial disorders. PMID- 1861211 TI - Liver involvement in Alpers disease. AB - Alpers disease consists of diffuse cerebral degeneration manifested as developmental delay, seizures, vomiting, and progressive neuromuscular deterioration, with liver disease and death. We report the clinical course of the liver disease, histologic progression of the hepatic lesions, and etiologic investigations in five patients (four girls, three kinships). All had grown and developed normally until seen at 6 to 36 months of age (mean 20 months), with vomiting (n = 5), progressive hypotonia (n = 3), or seizures (n = 2). All had been given anticonvulsants, including valproic acid in three. Liver disease was noted at a mean age of 35 months (range 9 to 67 months), with hepatomegaly (two patients), abnormal hepatic synthetic function (three) or transaminase values (three), and cirrhosis in one. Patients survived for a mean of 4.6 weeks (range 1 to 8 weeks) after the identification of liver disease; all died of hepatic failure. Results of evaluation for infectious and metabolic causes of liver disease and causes of degenerative neuromuscular disease were negative in all patients. Premortem liver biopsy specimens (n = 3) demonstrated an early lesion consisting of lobular disarray, microvesicular steatosis, periportal acute and chronic inflammation, and individual hepatocyte necrosis. Autopsy findings (n = 5) consisted of macrovesicular steatosis, massive hepatocyte dropout, and proliferation of bile ductular elements, with almost complete replacement of hepatocytes by proliferating bile ductular elements in two patients. Brain showed characteristic neuronal degeneration. We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction. PMID- 1861213 TI - Prevention of renal disease in insulin-dependent diabetes mellitus: a "responsibility" for the pediatrician? PMID- 1861212 TI - Immunologic studies in Turner syndrome before and during treatment with growth hormone. The Dutch Growth Hormone Working Group. AB - Immunologic studies of 14 girls with Turner syndrome were done before and during treatment with biosynthetic growth hormone (GH). Compared with control subjects, the patients before treatment had a decreased CD4/CD8 ratio and an increased number of cells bearing the natural killer cell marker CD16; serum immunoglobulin levels were within the normal range. During GH treatment some of the girls had a slight reduction in the percentage of CD20+ B cells, but we observed no impairment of B lymphocyte function as demonstrated by the normal in vivo antibody response to the primary antigen Helix Pomatia hemocyanin, administered 6 months after the start of GH treatment. The number of CD16+ natural killer cells returned to normal. Although the number of children with thyroid antibodies increased from two before treatment to five after 1 year, no conclusion about an adverse effect of GH is warranted, because the phenomenon might be part of the natural course of the disease. We conclude that girls with Turner syndrome have minor changes in some immunologic measurements and that GH treatment resulted in some alterations that have no effect on immune function. PMID- 1861214 TI - Therapeutic strategies for Langerhans cell histiocytosis. PMID- 1861215 TI - Presence of thyroid abnormalities in children with systemic lupus erythematosus. PMID- 1861216 TI - Nationwide survey of Kawasaki disease and acute rheumatic fever. PMID- 1861217 TI - Prevalence of congenital heart disease in patients with phenylketonuria. PMID- 1861218 TI - Multivariate assessment of traditional risk factors for chronic lung disease in very low birth weight neonates. The Newborn Lung Project. AB - All neonates (n = 581) with birth weights less than 1501 gm admitted to seven neonatal intensive care units in Wisconsin and Iowa were candidates for a study aimed at the multivariate assessment of risk factors for chronic lung disease while controlling for baseline severity of respiratory disease. Data from 361 neonates were analyzed for all risk factors except fluids; only neonates weighing less than 1200 gm were included (n = 220). Information on traditional risk factors for chronic lung disease was abstracted. A total of 110 (30%) of the analyzed neonates were oxygen dependent on day 30 of life. The following baseline factors were associated with increased risk of oxygen dependence in a joint multivariate model: lower birth weight (odds ratio 1.4/100 gm), higher baseline severity score (odds ratio 2.7/doubling at 32 weeks gestational age), lower gestational age (odds ratio 2.4/week at severity 0), Apgar score at 1 minute (odds ratio 1.6/2 points), male gender (odds ratio 1.9), and nonblack race (odds ratio 2.2). After adjustment for all baseline factors, patent ductus arteriosus, ventilator pressure at 96 hours, oxygen at 96 hours, and fluid intake were associated with oxygen dependence. Neonates with a low baseline severity score who remained oxygen dependent had a higher intake of fluid relative to output, whereas neonates with a higher baseline severity score had higher fluid intake and output. Lack of weight loss was associated with increased severity but not with oxygen dependence. The results of this study generally confirm the significance of previously reported risk factors for chronic lung disease in a multivariate setting but show that risk factors may not have the same impact in neonates with different baseline severity. PMID- 1861219 TI - Neonatal herpes gestationis. PMID- 1861220 TI - Staphylococcus aureus colonization after neonatal circumcision in relation to device used. PMID- 1861221 TI - Dose-dependent kinetics of orally administered 6-mercaptopurine in children with leukemia. AB - To determine whether the pharmacokinetics of 6-mercaptopurine (6-MP) would show dose dependency, we studied three different single oral doses in eight children (aged 3.6 to 15.1 years) with acute leukemia in remission. Marked interindividual differences in maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were observed when children received the 50 mg/m2 dose. This variability decreased when the doses were increased. Six of the eight children showed a disproportionate increase in the AUC with increasing doses; the other two had a proportionate relationship between the AUC and dose. Overall mean (+/- SD) Cmax and AUC values increased disproportionately (88 +/- 123, to 326 +/- 194, to 653 +/- 344 ng/ml for Cmax, and 147 +/- 180, to 451 +/- 177, to 1291 +/- 415 ng/ml per hour for AUC, respectively) when the dose increased from 50 to 87.5 mg/m2 and then to 175 mg/m2. The results suggest that a saturable first-pass metabolism of oral 6-MP occurs with increasing oral doses in some, but not all, children. Whether and to what extent this pharmacokinetic character of oral 6-MP affects the interindividual difference in systemic exposure to the drug in children with leukemia receiving maintenance therapy require further studies. PMID- 1861222 TI - Topical nitrogen mustard: an effective treatment for cutaneous Langerhans cell histiocytosis. AB - In 16 children with multisystem Langerhans cell histiocytosis (mean age 22 months, range 5 to 36 months) severe symptomatic skin involvement was treated with topical nitrogen mustard (mechlorethamine hydrochloride). In each case, rapid clinical improvement occurred within 10 days; subsequent complete healing was observed in 14 children, and partial healing in 2 others in whom treatment was a component of palliative care. Mean duration of treatment was 3.5 months (range 2 to 6 months). Systemic treatment was averted in 11 patients because response to topical therapy was so favorable, but bone marrow or respiratory failure led to a fatal outcome in 5 other patients. Adverse effects were minimal. One patient developed contact allergy to topical nitrogen mustard after 2 years of intermittent therapy, but was successfully desensitized and was then able to continue treatment. We conclude that the topical application of nitrogen mustard is an effective treatment for cutaneous Langerhans cell histiocytosis. Although adverse effects were minimal in the short term, there remains concern about the possibility of long-term cutaneous carcinogenicity. PMID- 1861223 TI - Prevention of mumps, measles, and rubella among hospital personnel. PMID- 1861224 TI - Uridine diphosphate glucose and uridine diphosphate galactose in galactosemia. PMID- 1861225 TI - Therapy for hereditary nephrogenic diabetes insipidus. PMID- 1861226 TI - Management of congenital diaphragmatic hernia. PMID- 1861227 TI - Methotrexate hepatotoxic effects in children with juvenile rheumatoid arthritis. PMID- 1861228 TI - Diazepam for prevention of recurrence of febrile seizures. PMID- 1861229 TI - Effect of early antibiotic therapy for streptococcal pharyngitis on recurrence rates. PMID- 1861230 TI - Mean corpuscular volume as an aid in identifying the cause of hematuria. PMID- 1861231 TI - Bacterial endocarditis after minor orthodontic procedures. PMID- 1861232 TI - High-frequency jet ventilation in respiratory distress syndrome. PMID- 1861233 TI - More on growth hormone therapy for otherwise normal short children. PMID- 1861234 TI - The development and structure of principal fibers and cellular cementum in rat molars. AB - The principal fibers and cellular cementum were examined in various developmental stages in rat molars by light and electron microscopy, and their development and structure were studied. The principal fibers increased in thickness with root development. At any given stage, the principal fibers consisted of small fiber bundles on the cementum surface and showed a branching structure. Sharpey's fibers also showed a similar branching structure and increased in thickness, as traced superficially in the cementum. It was suggested that the principal fibers increased in thickness by means of the aggregation of fiber bundles. The development of cellular cementum was divided into two (early and late) phases on the basis of the fiber arrangement. The early cementum was believed to contain a few Sharpey's fibers and many randomly arranged intrinsic fibers. The late cementum contained thicker Sharpey's fibers with branches and the intrinsic fibers which appeared to encircle Sharpey's fibers and/or meander among them. PMID- 1861235 TI - Proceedings of the 18th Symposium on Pharmacological Activity and Mechanism. September 19-21, 1990, Asahikawa. PMID- 1861236 TI - Comparative studies on the anticonvulsant activity of lipophilic derivatives of gamma-aminobutyric acid and 2-pyrrolidinone in mice. AB - Anticonvulsant activity, degradation into gamma-aminobutyric acid (GABA), and concentration in brain of 1-dodecanoyl-2-pyrrolidinone (I), a lipophilic derivative of a lactam of GABA, were compared with those of N-dodecanoyl GABA (II) and 1-dodecyl-2-pyrrolidinone (III) to get information about their pharmacological mechanisms. Compounds I and II degraded into GABA in mouse liver homogenate, gradually into GABA in brain homogenate and more slowly in plasma. Compound III had no degradation in the biological media. The derivatives administered intraperitoneally had dose-dependent anticonvulsant activity on picrotoxin-induced seizure in mice. Their anticonvulsant activities were changed by the time intervals between pretreatment of derivatives and administration of picrotoxin. Compounds II and III showed anticonvulsant activity on pentylenetetrazole-induced seizure and a prolonged sleeping time induced by sodium pentobarbital in mice. However, these three derivatives never significantly increased the GABA level in mouse brain after intraperitoneal administration compared to the endogenous GABA level. They were detected as intact derivatives in the brain. In the previous report, we demonstrated the anticonvulsant activity of sodium dodecanoate. These results suggested that the dodecyl chain of derivatives may be important for their anticonvulsant activities and I does not act as GABA via prodrug. PMID- 1861237 TI - Antioxidative effect of protoporphyrin on lipid peroxidation in tissue homogenates of intravenously administered rats. AB - Effect of intravenous administration of protoporphyrin IX (PP) on lipid peroxidation was studied in rats. PP and/or PP-derived porphyrins were found to be mainly distributed in livers, spleen and lungs. Dose-dependent decreases in the Fe2+ and L-ascorbic acid-stimulated lipid peroxidation in homogenates of livers and dose-dependent increases in porphyrin concentration in livers were observed after the PP injection. In the experiments with a 20 mg/kg dose of PP, the peroxidation level in the liver homogenates reached its minimum level during the period of 3 to 24 h accompanying the high porphyrin concentration in livers after the administration. After 96 h, a relatively high porphyrin concentration was still retained, but decreases in the peroxidation levels had ceased. PP administration caused a dose-dependent decrease in the endogenous lipid peroxides in livers within 0.5 h and the low levels were maintained throughout the course of the 168-h study. These results clearly show that the administered PP is distributed in the liver and inhibits the lipid peroxidation in vivo. PMID- 1861238 TI - Improvement in wound healing by epidermal growth factor (EGF) ointment. II. Effect of protease inhibitor, nafamostat, on stabilization and efficacy of EGF in burn. AB - The healing effect of human epidermal growth factor (hEGF) on second degree burn was studied in rats. No improvement in wound healing was found on topical application of EGF alone to burn sites, but an ointment containing EGF and nafamostat mesilate (NM), a protease inhibitor, accelerated the healing rate of burns. The dry weight of the granulation tissue on the wound site in the group treated with EGF plus NM ointment did not change, although that in other groups decreased. After treatment with EGF ointment containing NM, the content of uronic acid, as an index of acid mucopolysaccharide, at 3 d after burn rapidly increased and had recovered to nearly normal levels at 7 d after burn. However, the uronic acid content in the other groups (control, EGF alone, and NM alone) showed a higher value at 7 d than at 3 d. When compared with the control values significant increases in hydroxyproline, as an index of collagen, in the wound site were observed at 7 d after treatment with EGF ointment containing NM. The degradation of [125I]EGF in burned tissue homogenate decreased significantly in a concentration-dependent manner in the presence of NM. Body weights did not change after treatment with EGF plus NM ointment, although the body weights of other treatment groups decreased after burn, suggesting that EGF ointment containing the protease inhibitor, NM, alleviated the effects of burn shock. These findings indicate that the stabilization of EGF at the wound site is an important factor for the expression of its healing effects. PMID- 1861239 TI - Stimulatory effect of guanine nucleotides on prostaglandin E1 binding to murine renal outer medulla. AB - Prostaglandin E1 (PGE1) specifically bound to the membrane prepared from murine renal outer medulla. The extent of binding of [3H]PGE1 to the membrane was increased about 4-fold by guanosine triphosphate (GTP) and its analogs, but the dissociation of bound [3H]PGE1 from the membrane was in turn enhanced by GTP gamma S. Scatchard plot analyses revealed that GTP gamma S increased the binding affinity more than 2-fold without a major change in the number of binding sites. When [3H]PGE1-bound proteins were cross-linked in the membrane by dithiobis (succinimidyl propionate), bound [3H]PGE1 was no longer dissociated by GTP gamma S treatment, suggesting that cross-linking produced a stable complex of PGE receptor with a GTP-binding protein. The cross-linked [3H]PGE1-specifically bound proteins solubilized from the membranes labeled with [3H] PGE1 in the presence or absence of GTP gamma S were eluted as an apparently single radioactive peak at the same position of Mr = 15000 by gel filtration, indicating that the PGE receptor forms a complex with a GTP-binding protein regardless of the treatment with GTP gamma S by which [3H]PGE1 binding is promoted. The ability of GTP gamma S to stimulate [3H]PGE1 binding was eliminated by pretreatment of the membrane with pertussis toxin, but not cholera toxin, indicating that the PGE receptor is coupled to a pertussis toxin-sensitive GTP-binding protein. PMID- 1861240 TI - Phacoemulsification: the favored surgical technique. PMID- 1861241 TI - Iris modifications following extracapsular cataract extraction with posterior chamber lens implantation. AB - We prospectively examined 94 eyes of 93 consecutive patients who had planned extracapsular cataract extraction or phacoemulsification with posterior chamber intraocular lens (IOL) implantation. The observed postoperative iris biomicroscopic modifications are described and classified. Iris synechial formation was more frequently observed in eyes with pseudoexfoliation syndrome, when an irregular anterior capsulotomy was performed, when the IOL was other than in the bag, and in cases of postoperative fibrinous exudation. Synechias occurred more frequently in intraoperatively injured iris areas. Pupil capture was the only postoperative iris modification that was observed to affect visual acuity. The maximal postoperative dilation was greater and the pupillary photic reaction was significantly less modified postoperatively (P = .0058) when the IOL was fixated within the capsular bag. PMID- 1861242 TI - Divide and conquer nucleofractis phacoemulsification: development and variations. AB - Cataract extraction by phacoemulsification of the lens in situ can be accomplished by a technique incorporating continuous curvilinear capsulorhexis (CCC), deep central sculpting of the nucleus, and manual cracking ("nucleofractis") and subsequent fragmentation and emulsification of the remaining nucleus. This "divide and conquer" nucleofractis technique of phacoemulsification is uniquely suited to the constraints that CCC, which provides excellent conditions for well-centered in-the-bag placement of intraocular lenses, imposes upon cataract extraction. The cracking and fragmentation maneuvers allow phacoemulsification to be extended to patients with hypermature and brunescent lenses, as well as small pupils, who are not normally considered good candidates for the technique. PMID- 1861243 TI - Optical design of low index intraocular lenses. AB - The effect of shape of low index (1.43) intraocular lenses on optical performance of pseudophakic eyes was investigated. A range of image quality criteria was used. The optimum lens for on-axis vision was biconvex, with the more curved surface facing the cornea. For small off-axis angles, optimum lens shape varied with the ocular parameters. A recommended range of intraocular lenses is plano convex (with the curved shape facing the cornea) to equi-convex. Compared with conventional poly(methyl methacrylate) lenses (1.492 index), optimum lens shapes of low index lenses were less sensitive to changes in eye parameters and lens fitting position. The magnitudes of aberration of pseudophakic eyes varied more with changes in lens shape and lens position in low index lenses than in conventional lenses. PMID- 1861244 TI - Cataract surgery in anticoagulated patients. AB - A prospective study was performed on 31 patients having planned extracapsular cataract extraction with posterior chamber intraocular lens implantation. The patients were considered to be anticoagulated because of the medications they were taking. The patients were instructed to continue their usual medications throughout the perioperative period including the day of surgery. All patients had routine narcoleptic sedation and retrobulbar anesthesia. The surgical technique was altered to use an inferior corneal traction suture and a single planed clear corneal incision. No intraoperative or postoperative anterior chamber bleeding was seen. The observed complications were increased awareness of corneal sutures, increased endothelial cell loss, delayed visual rehabilitation from with-the-rule astigmatism, and transient corneal edema. All patients achieved 20/40 or better visual acuity without corneal edema by three months post surgery. PMID- 1861246 TI - Postoperative cellular reaction on surface modified intraocular lenses in living human eyes. AB - Specular microscopy was performed to evaluate the postoperative cellular reaction on surface modified poly(methyl methacrylate) intraocular lenses (IOLs) (Ioptex Research, Inc., model U370) in 40 eyes of 36 patients who had extracapsular cataract extraction with implantation of the surface modified IOLs. The cellular elements observed were fibroblast-like cells, histiocytes, and giant cells. Gray amorphous depositions, part of which were sometimes recognized as interference fringes or interference colors, formed a layer in the center of the optics. These depositions were probably caused by the adsorption from aqueous humor. In subclinical cases, only a few histiocytes and giant cells were recognized in the optic center and the optic periphery was free of the cells during our observation. Within two months of surgery most of the cells had disappeared. In vivo specular microscopy showed no manufacturing defects on the implanted lenses. Our findings suggest that, although there was a postoperative cellular reaction on the surface modified IOLs, they were biocompatible. PMID- 1861245 TI - Natural history of corneal astigmatism after cataract surgery. AB - Little information on the natural course of corneal astigmatism following cataract surgery exists. We report a prospective, computerized analysis of postoperative astigmatism, based on keratometry measurements, of 137 cases of extracapsular cataract extraction with intraocular lens implantation performed by one surgeon. No sutures were cut postoperatively. Surgery induced 1.44 diopters (D) of with-the-rule astigmatism at one month, which declined at a rate of 0.77 D and 0.35 D per month for the next two months, respectively, with a more gradual decline thereafter. The mean surgically induced astigmatism at the last postoperative visit ranged from 0.29 D at six months (minimum follow-up) to 1.23 D at 48 months; both were against-the-rule. Mean follow-up was 28.92 months. These findings may be technique specific and suggest that (1) corneal curvature continues to change slowly even two to four years postoperatively; (2) most patients develop against-the-rule astigmatism, thus more with-the-rule astigmatism is desirable in the early postoperative period; (3) selective suture removal is necessary only when significantly more than 3.00 D of surgically induced with-the-rule astigmatism is present. PMID- 1861247 TI - Pathology of fixation fibrosis on intraocular lenses. AB - Ocular tissues frequently form a special kind of reactive fibrosis with distinct cellular strands that anchors prominent surface irregularities of lens implants- haptics, manipulation holes, or borders--to adjacent ocular structures and helps fixate the implant in the eye. The strands originate in reactive proliferation of chemotactically attracted sessile macrophages on the surface of lens implants. They are cellular in their early stages and may undergo secondary fibrosis or hyalinization. The formation of these strands is called "fixation fibrosis." An initial description of the pathology of this complicated process is presented. PMID- 1861248 TI - Decentration of intraocular lenses implanted after intercapsular cataract extraction (envelope technique). AB - Pseudophakos decentration produces symptoms such as glare, halos, and other visual aberrations. We have reviewed 161 eyes of patients who had an intercapsular cataract extraction with intraocular lens (IOL) implantation with a follow-up of at least six months. Mean decentration was 0.54 mm. It was 0.46 mm for the lenses implanted symmetrically in the bag, 0.65 mm for those implanted in the sulcus, and 0.91 mm for those implanted asymmetrically (bag-sulcus). The differences between the lenses fixated in the bag and those asymmetrically situated were statistically significant (P less than .001). Circular looped lenses (360-degree encircling loop) decentered less (mean 0.28 mm) than modified C-loop lenses (mean decentration 0.63 mm) and modified J-loop lenses (mean decentration 0.60 mm). These differences were statistically significant (P less than .001). The differences were also significant if we considered only the lenses implanted in the bag (mean decentration 0.20 versus 0.59 and 0.54, respectively) (P less than .0001). PMID- 1861249 TI - Experimental evaluation of a phakic anterior chamber implant in a primate model. Part I. Clinical observations. AB - Anterior chamber intraocular lenses were implanted in phakic cynomolgus monkey eyes and followed clinically over two years. Significant observations included erosion and/or uveal envelopment of the haptic and a decrease in endothelial cell counts. There was good positional stability, no significant inflammation, initial ocular hypotension that returned to normal intraocular pressure, and no evidence of cataracts or cystoid macular edema. PMID- 1861250 TI - Experimental evaluation of a phakic anterior chamber implant in a primate model. Part II. Pathology. AB - Anterior chamber intraocular lenses were implanted in 50 phakic primate eyes and followed by serial histopathology for two years. Significant observations included corneal endothelial alterations, haptic erosion into and encapsulation by peripheral iris and ciliary body, and chronic low grade inflammation. PMID- 1861251 TI - Endophthalmitis investigative protocol: a plan for source identification and patient protection. AB - A survey of randomly selected ophthalmic outpatient surgical facilities revealed a lack of established investigative protocols to follow when postoperative endophthalmitis occurs. The survey also provided information about the incidence of endophthalmitis, the microorganisms encountered, and the precautions used to prevent postoperative infections. We present an endophthalmitis investigative protocol which provides a task list, investigation forms, incidence log, and quality assurance measures to identify patients at risk and to minimize the risk of recurrence of this rare but serious complication of ophthalmic surgery. This standardized protocol will also assist in source identification when aseptic iritis occurs postoperatively. The purpose of this paper is to stimulate a dialogue which may result in an international standard for an endophthalmitis investigative protocol. PMID- 1861252 TI - Report of the American Society of Cataract and Refractive Surgery International Committee on Standards and Quality Control for Ophthalmic Instruments and Devices. PMID- 1861253 TI - The chip and flip phacoemulsification technique. AB - The "chip and flip" phacoemulsification technique increases safety and control within the capsular bag. The surgical maneuvers use a two-handed technique through a small curvilinear capsulorhexis. PMID- 1861254 TI - The 1.97 cent solution: low tech capsulorhexis and hydrodissection. AB - Capsulorhexis is becoming the favored technique for performing anterior capsulectomy. This report describes a simple method for performing capsulorhexis and nuclear hydrodissection without the use of viscoelastics or specialized instruments. PMID- 1861255 TI - Ophthalmic pre-inked marking pad. AB - Various markers that facilitate incision and suture placement are available. The majority are used in conjunction with a surgical marking pen or ink. This report describes a new, disposable pre-inked marking pad which is conveniently packaged, easy to use, and compatible with most markers. The pad is saturated with gentian violet ink which enables an ideal transfer of inked marks from the marker to the eye or skin. The ink marks remain on the tissue for two to four hours before fading, even on wet and moist surfaces such as the cornea and sclera. PMID- 1861256 TI - Consultation section. Assuming the presence of a symptomatic, significantly dense cataract, or a cataract that interferes with evaluation and/or treatment of the retina. PMID- 1861257 TI - Is there a case for the 10 mm wound? PMID- 1861258 TI - Sutureless closure for exchange surgery of intraocular lenses. PMID- 1861259 TI - In vitro, adhesive fixation of a posterior chamber lens optic: implications for lens centration and posterior capsule opacification. PMID- 1861260 TI - Filters and antibiotics in irrigating solution for cataract surgery. PMID- 1861261 TI - Post capsulotomy complication. PMID- 1861262 TI - Public health aspects of a refugee camp. AB - The explosion in the number of refugees throughout the world has led to the development of a new medical speciality; Migration Medicine. Such a speciality has a strong public health dimension. Addressing the public health needs of refugees especially in developing countries is one of the few challenges of practising public medicine which gives measurable results in weeks rather than years. Whilst I was a trainee in Public Health Medicine in Glasgow, UK, I was seconded to Medecins Sans Frontieres ('doctors without borders') to act as Medical Co-ordinator of a relief operation for refugees from Sudan. This paper discusses some of the lessons that the experience taught me which have application to many refugee situations throughout the world. PMID- 1861263 TI - Reducing the risks of solvent misuse. PMID- 1861264 TI - The psychological effects of disaster work: implications for disaster planning. AB - The paper focuses on the psychological consequences of disaster work. The issue of identifying staff who may be more vulnerable to psychological distress is discussed as is the need for services to plan psychological screening and support for staff who will be exposed to the trauma of dealing with the aftermath of disasters. It is concluded that active steps need to be taken to incorporate psychological aspects into disaster planning. Specifically, attention should be paid to staff selection, training, use of resources, supervision, debriefing, counselling and feedback. PMID- 1861266 TI - Foodborne infections and poultry. PMID- 1861265 TI - Problems of review and discharge. Is a Tribunal necessary? PMID- 1861267 TI - The effect of the consumption of red kidney beans on the growth rate of rats and the implications for human populations. PMID- 1861268 TI - Evaluation of an intensive 'train-the-trainer' course in AIDS counselling in Zimbabwe. AB - The anticipated increase in the number of people with HIV infection and AIDS in Zimbabwe, together with those who have associated worries, will place extra demands upon clinical and counselling services in the coming decade. To meet these demands, a wide range of health care staff will have to acquire specialist counselling skills. For this reason, an intensive two-day HIV/AIDS train-the trainer counselling course was run at the Family Counselling Unit (FCU), Harare, in April 1990. The aim was to teach training and supervision skills in AIDS counselling so that those professionals with experience could confidently teach others counselling skills for people with HIV/AIDS. The structure, content and evaluation of the course are presented here. Overall, the course was positively evaluated by the 42 trainees who came from Harare and other towns in Zimbabwe. The different teaching activities (role play, discussion) and course objectives (to develop specialist skills, address diverse problems) were especially well thought of. However, a few trainees were critical of the teaching format and lack of time available for teaching. This training experience may help others in establishing courses for the training of trainers in AIDS counselling elsewhere. PMID- 1861269 TI - First aid and first aiders who work in health food, processing and light engineering in Nottingham. AB - One hundred and forty nine first aiders working in a health authority, 26 in a light engineering company and 35 in food processing plants completed an anonymous questionnaire about their training and first aid work. Information was also gathered on views about its value, the role of cash bonuses and its promotion amongst other staff. The response rate was 88%. The majority of first aiders were in their 30s and had practised first aid for less than a decade. At least 80% intended to revalidate their certificate and continue to practise. First aid was used most in food processing plants and least in the health authority. Offers of help had seldom been refused. Over 90% of respondents thought first aid was worthwhile. PMID- 1861270 TI - House dust mite control: a public health issue. PMID- 1861271 TI - Community-acquired pneumonia: the clinical dilemma. AB - Community-acquired pneumonia (CAP) is the sixth most common cause of death in the United States. Despite its frequency and mortality, specific etiologic diagnosis remains a major clinical challenge. The organisms most commonly implicated in CAP are Streptococcus pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila, Haemophilus influenzae, Chlamydia pneumoniae (TWAR), and viruses. Clinical and radiographic criteria have proven to be of little value in determining the etiology of CAP. Laboratory studies, including Gram's stain and culture of sputum, have also been shown to be of severely limited value to the clinician faced with the patient with CAP. Antibiotic therapy must, therefore, generally be empiric. Regimens including erythromycin either as a single agent or coupled with an aminoglycoside or cephalosporin appear to be most efficacious. PMID- 1861272 TI - Pet-associated lung diseases. AB - With the development of new diagnostic techniques, several diseases have emerged in recent years as zoonotic or potentially zoonotic. Even so, most pet-associated illnesses are infrequent, and therefore, health care providers may not be familiar with their manifestations or with the appropriate preventive measures. This article reviews the epidemiology, diagnosis, therapy and prevention of lung disorders acquired from dogs and cats. PMID- 1861273 TI - Pneumonia in children. PMID- 1861274 TI - Pneumonia in the elderly. AB - Pneumonia is not only a major cause of death for elderly persons, but also imposes substantial personal morbidity and burdens on the health care system. Timely, accurate diagnosis and therapy depend on recognition of important differences in the pathogenesis of pneumonia according to the settings in which it occurs. Active elderly persons living in the community, institutionalized seniors with "nursing home pneumonia," and those with hospital-acquired infections have different microbial causes of their respiratory infections that, together with altered host defenses and iatrogenic factors, dramatically influence outcomes. The presence of other common medical illnesses in older persons obscures the clinical presentations of pneumonia, predisposes to respiratory infection, and adversely influences prognosis. These clinical relationships and the variability and vulnerability of individual patients underlie largely empiric, setting-specific antimicrobial therapy. Whenever possible, prevention of this devastating illness is essential. PMID- 1861275 TI - Legionnaires' disease. AB - The Legionella bacillus is a relatively common pulmonary pathogen that has been responsible for a number of outbreaks of respiratory illness this century. Not until 1976, however, after exciting epidemiologic and microbiologic investigation, was the organism isolated and identified. Legionnaires' disease does not have a characteristic radiographic appearance, but certain features may alert the clinician to its presence. It often rapidly progresses to a lobar pneumonia that may not respond immediately to treatment. The radiographic findings lag behind clinical improvement, and radiographic resolution is prolonged. Organ transplantation patients often present with ill-defined, rounded, pleura-based opacities that may simulate pulmonary infarction and can cavitate. PMID- 1861276 TI - Bacterial lung abscess: a review of the radiographic and clinical features of 50 cases. AB - The radiographic and clinical features of 50 patients with documented bacterial lung abscess are presented. Neither clinical nor radiographic features permit a specific diagnosis of lung abscess to be made; microbiologic or histopathologic material is needed to establish the diagnosis. A surprising percentage of patients (18%) had radiographically occult lung abscesses that were diagnosed only at the time of surgery or autopsy. Possible causes for and means of avoiding this diagnostic pitfall are presented. PMID- 1861278 TI - Surgical management of thoracic empyema. AB - Thoracic empyema usually results from pulmonary infection or thoracic surgery. Antibiotic therapy is an essential part of the treatment, but surgical techniques to drain the pleural fluid and obliterate the empyema space often are required. A wide range of closed and open surgical techniques are available. This article reviews the various surgical options for the treatment of nontuberculous bacterial empyema secondary to pulmonary infection in the patient with a normal immune response. Emphasis is placed on a thorough understanding of the pathophysiology and natural history of empyema for selection and timing of appropriate treatment. Thoracic imaging techniques play a substantial role in the evaluation and treatment of empyema and in assessing the outcome of surgical therapy. PMID- 1861277 TI - Pleural infections: a clinical-radiologic review. AB - Pleural space infection is a common disorder that may result from a wide variety of causes and is associated with a wide range of etiologic agents. The authors reviewed retrospectively records of 102 patients with discharge diagnoses of empyema and/or bronchopleural fistula. Chest radiographs and computed tomography closest to the time of initial diagnosis were evaluated separately. In 78 cases of empyema, the etiologies included primary pulmonary infections (49%), postsurgical (23%), traumatic (11.5%), intraabdominal pathology (5%), and unknown (11.5%). In 24 cases of bronchopleural fistulas, the etiologies were previous surgical procedures (37.5%), pulmonary infections (37.5%), traumatic (4%), and unknown (21%). PMID- 1861279 TI - A clinico-epidemiological study of sickle cell anaemia in Saudi Arabia. AB - Ninety-nine Saudi Arabian children aged between 3 months and 15 years attending the sickle cell anaemia (SCA) clinic were studied using a review of case notes and an interview at clinic visits. All the patients come from the southwest and west area of Saudi Arabia. Despite the lack of infant screening for SCA, 73 per cent were diagnosed before the age of 3 years, reflecting severe early symptoms of the disease. The serious complications of SCA were two times higher, the number of admissions were three times higher and the attack rate for pneumococcal meningitis was nine times higher in our study population than previously reported from the Eastern Province of the country. Hand-foot syndrome was the commonest complication affecting 58 per cent of the children. It has been stated previously that there is no need to give penicillin prophylaxis to SCA children in Saudi Arabia, based on the observations in the Eastern Province only. Our study shows that SCA in western and southwestern population of Saudi Arabia is as severe as is described in American blacks. Therefore, we recommend penicillin prophylaxis to be given to the SCA children in the southwest and west regions of the country. PMID- 1861280 TI - Outcome of low birth weight infants in a West African village. AB - Low birthweight (LBW) infants are at risk of increased mortality, impaired growth, and increased morbidity. We studied the progress of all LBW infants (less than 2.5 kg) born in a West African village where there is a resident pediatrician and midwife. There were 426 live births during the 8 years studied of which 42 (10 per cent) were of LBW. There were 17 infant deaths (IMR = 40/1000). Mean birthweight and gestation of infants dying in the first year were significantly lower than those of all live birth (2.33 kg v. 2.99 kg, P less than 0.001; 36.9 w v. 38.9 w, P less than 0.05). The mean weights of the 32 surviving LBW infants (15 preterm, 17 full term, small for gestational age) were compared with those of 32 full term, appropriate for gestational age matched controls over the first year. Growth velocities of paired groups were identical. The significant differences in weight at 1 year (P less than 0.005) reflected those at birth (P less than 0.001). There were no significant differences in clinic attendance rate or incidence of diarrhoea and respiratory disease between the four groups. We conclude that LBW is a strong risk factor for infant mortality, but not for diarrhoeal and respiratory morbidity in a community with ready access to obstetric and pediatric care. PMID- 1861281 TI - Infant feeding and growth in rural Ghana: is the use of the traditional fermented porridge a case for early supplementation? AB - Thirty infants were studied longitudinally for 6 months. Breast milk and intakes of supplements were measured at the first and third months post-partum. Mode of feeding, morbidity, and weights were recorded monthly. Variations in growth were found to be related to levels of breast milk intakes, and timely and effective supplementation with the traditional weaning porridge prepared from fermented maize dough. No diarrhoeal incidence was recorded before 3 months. It is suggested that coupled with true demand breast feeding, the traditional weaning porridge could adequately support growth if introduced on time, even when breast milk intakes are less than optimal. PMID- 1861282 TI - Bottle use for infant feeding in developing countries: data from the demographic and health surveys. Has the bottle battle been lost? AB - This paper uses data from 22 national surveys in developing countries to estimate the use of bottles for feeding of infants under 6 months of age. These data were collected in the context of the Demographic and Health Surveys programme (DHS) between 1986 and 1989. Bottle use appears to be very common in most countries. Only six of the 22 countries had levels of bottle use of less than 20 per cent, and all these countries are in sub-Saharan Africa. The policy implications are discussed briefly. PMID- 1861283 TI - Henoch-Schonlein syndrome in Saudi Arabia. AB - A retrospective study was carried out on 40 children from Saudi Arabia with Henoch-Schonlein syndrome to delineate its clinical pattern. More than 50 per cent of the cases occurred in winter. There was no apparent causal relationship with B-haemolytic streptococcal infection. All patients had skin rash. Fifty eight per cent had gastrointestinal manifestations, 58 per cent had joint manifestations and 38 per cent had renal manifestations. The main clinical features of Henoch-Schonlein syndrome in Saudi children are comparable to those reported elsewhere. PMID- 1861284 TI - Effects of the relative importance of different factors and their degree of interactions on child growth. AB - The purpose of the study is to determine duration of satisfactory breast feeding in health breast-fed infants of mothers attending Maternal and Child Health Centres in the three towns of Khartoum Province. The main objective of this paper is to compare samples in terms of effects of different factors on child growth. The infants' weight and length were measured in the first few days after birth and from then on weight was measured every 2 weeks and length every 4 weeks up to 1 year. The results presented have been analysed throughout in terms of factors that affect weight gain. In Khartoum North sample weight gains were lowest in the first 3 months, but thereafter were higher and almost the same as the NCHS reference. In Khartoum and Omdurman, however, growth from birth to 3 months exceeded the NCHS standard, but from 3 to 6 months were significantly less than the reference. Level of hygiene, health of the mother during pregnancy, sex, housing, and town were found to be the factors affecting weight gain of infants from 0 to 3 months of age, while income, supplementary feeding, occupation, water, infections, and town were found to be the factors affecting weight gain of infants from 3 to 6 months of age. PMID- 1861285 TI - Plasma iron and iron proteins in erythrocyte glucose-6-phosphate dehydrogenase deficient newborns. PMID- 1861286 TI - The effect of vitamin A prophylaxis on morbidity and mortality among children in urban slums in Bombay. PMID- 1861287 TI - Can low income women in developing countries afford artificial feeding? PMID- 1861288 TI - Is follow-up formula from 6 months onwards necessary? PMID- 1861289 TI - Shigellosis. PMID- 1861290 TI - Retraction. The effect of an alpha-2 agonist on bladder function and cord histology after spinal cord injury. PMID- 1861291 TI - Papers presented at annual meeting of the Section of Urology, American Academy of Pediatrics. Boston, Massachusetts, October 5-10, 1990. PMID- 1861292 TI - Collagen and elastin in the normal fetal bladder. AB - The development of muscle, collagen and elastic fibers was studied histologically in 15 human fetal bladder specimens. Muscle thickness progressively increased and the relative collagen content in the muscle decreased during gestation. The ratio of thick-to-thin collagen fibers also decreased, whereas elastic fibers increased. These findings document the normal process of maturation of the fetal bladder and serve as a basis for comparison with congenitally obstructed fetal bladders. PMID- 1861293 TI - Collagen and elastin in the obstructed fetal bladder. AB - Histological findings of muscle, collagen and elastin in obstructed fetal bladders were compared with those of age-matched controls. Muscle thickness was markedly increased, however, the relative collagen content in the muscle was decreased. The ratio of thick-to-thin collagen fibers was markedly increased as was the amount of elastin. These findings suggest that the ratio of thick collagen to elastin has an important role in determining the compliance of the obstructed fetal bladder. PMID- 1861294 TI - The use of intravesical oxybutynin chloride in children with neurogenic bladder. AB - Intravesical oxybutynin chloride was administered to 10 children with neurogenic bladder (myelomeningocele in 9 and imperforate anus in 1) and urinary incontinence refractory to regimens of intermittent catheterization and oral anticholinergic medication. Therapy consisted of instillation of 5 mg. crushed oxybutynin chloride in 10 cc sterile saline twice daily. Of the children 5 (50%) became completely dry day and night, 3 (30%) achieved daytime continence alone, and 2 did not improve clinically and remained in diapers. Urodynamic study revealed increases in bladder capacity up to 335% over baseline and decreases of maximum filling pressures to 63%. No local or systemic side effects were noted. Surgical bladder augmentation was avoided in those who clinically responded to this therapy. PMID- 1861295 TI - Urodynamic evaluation of the continence mechanism following urethral lengthening- reimplantation and enterocystoplasty. AB - In an attempt to create continence in myelomeningocele children we performed urethral lengthening/submucosal reimplantation, a form of bladder neck reconstruction, to create a valve allowing catheterizable access to the bladder. We present the urodynamic findings of 23 patients 4 to 89 months (mean 43.1 months) after bladder neck reconstruction and enterocytoplasty to determine the continence mechanism of this 1-way valve and characteristics of the augmented bladder. Standard cystometrograms with simultaneous pressure recording of the submucosal portion of the neourethra were undertaken with a 10F, triple lumen, urethral pressure profile catheter. Baseline pressures in the submucosal neourethra were higher than in the bladder (mean 25.3 versus 13.4 cm, water, p less than 0.001). Submucosal tunnel and bladder pressures paralleled throughout filling, with mean tunnel pressures remaining greater at the time of first (53.6 versus 45.5 cm. water, p less than 0.01) and peak (62.9 versus 55.8 cm. water, p greater than 0.05) cystoplasty contractions. Bladders augmented with detubularized ileum had fewer significant contractions (greater than 40 cm. water) than other types of cystoplasties (36% versus 92%) and over-all they had first and peak contractions at greater volumes and lesser magnitude. We conclude that continence following urethral lengthening/reimplantation results from an anatomical arrangement allowing transmission of dynamic bladder pressure changes to the submucosal neourethra and that urethral pressure exceeds bladder pressure throughout filling. Additionally, our data suggest that detubularized ileum provides a large capacity, low pressure reservoir suitable for augmentation. PMID- 1861296 TI - Urodynamic evaluation of the patient with an imperforate anus: a prospective study. AB - Prospective urodynamic evaluation of 14 patients with an imperforate anus revealed detrusor-sphincter dyssynergia in 4. Subsequent contrast voiding cystourethrograms demonstrated radiographic changes in all 4 cases, consisting of bladder trabeculation, new onset of vesicoureteral reflux or hydroureteronephrosis. Of the 4 patients 3 had a high (supralevator) imperforate anus, while 1 had a low (infralevator) lesion. Two patients had bony vertebral abnormalities and 2 had normal plain radiographs and magnetic resonance imaging of the spine. Therefore, early urodynamic study is recommended for all patients with an imperforate anus and it should complement neonatal uroradiographic evaluation. The finding of detrusor-sphincter dyssynergia should alert the urologist to the need for adjunctive management. PMID- 1861297 TI - Renin production after experimental extracorporeal shock wave lithotripsy: a primate model. AB - Since the advent of extracorporeal shock wave lithotripsy (ESWL) concern has surfaced as to the long-term risk of the development of hypertension, as well as risk to the developing kidney. To study this concern 8 infant and 3 adult rhesus monkeys (Macaca mulatta) underwent treatment with the XL1 experimental lithotriptor to 1 kidney varying the amount of voltage and shocks. Followup consisted of measurement of renin levels and quantitative renal scans, using 131iodine hippurate to calculate effective renal plasma flow. In the infants a slight change was noted in the absolute effective renal plasma flow of the treated kidney versus the untreated side but it was not statistically different. When indexed to body surface area in the growing animal, there was a statistically significant decrease in renal function. However, peripheral renin levels were markedly elevated in the infants at 3 weeks, and they gradually declined during the 6-month period, although levels remained elevated over baseline. The adults also had central renin levels drawn from the renal vein on the treated side, and there was a close correlation with the peripheral levels, which peaked at 3 weeks and returned to normal. Thus, it seems that at least in the short term renin production is increased in infants more than adults. This finding may be an indicator as to renal damage and is a possible explanation for hypertension occurring after ESWL. PMID- 1861298 TI - Elevated intravesical pressure causes arterial hypoperfusion in canine colocystoplasty: a fluorometric assessment. AB - Since 1988 there have been 15 reported cases of late, spontaneously ruptured intestinal cystoplasties at bowel sites remote from the anastomosis. Ischemic necrosis has been suggested as a possible etiology. We examined this hypothesis by quantifying the uptake of intravascular fluorescein in the augmented bowel of adult mongrel canines. There was a statistically significant decrease in fluorescein uptake at high intravesical pressures, which appeared to be most pronounced at the antimesenteric border. This laboratory study supports a recent clinical report of histological changes pathognomonic for chronic ischemia in the augmented bowel of patients with spontaneous rupture. PMID- 1861299 TI - Viability and functional characteristics of enterocystoplasty after ligation of the vascular pedicle. AB - A canine model was developed to evaluate the effect of ligation of the mesenteric blood supply of enterocystoplasty. In 5 dogs with an ileocystoplasty and 6 with a gastrocystoplasty the blood supply was interrupted 4 months postoperatively. Re exploration 2 to 8 weeks later revealed sufficient collateral blood flow to maintain integrity of the bowel wall and none of the animals had urine leak or other signs of perforation. Two animals had a significant decrease in the size of the cystoplasty. Intraoperative measurements of bowel viability after pedicle ligation were not predictive of the outcome. The functional outcome after pedicle division seems to be variable and probably reflects how well the patch has been vascularized before interruption of the blood supply. The augmented bladder may remain viable if sufficient time has elapsed to allow revascularization of the intestinal segment before its mesenteric blood supply is divided. PMID- 1861300 TI - Seromuscular enterocystoplasty in rats. AB - Enterocystoplasty is commonly used in clinical practice. Many of its undesirable effects, that is infections, stones, mucus production, absorption of urinary components into the blood stream and risk of cancer, result from the intestinal mucosa lining the urinary tract. We report on the feasibility of creating an enterocytoplasty with a seromuscular colonic segment that acquires a transitional epithelial lining. Augmentation enterocystoplasty was performed in 51 male, 500 gm., Sprague-Dawley rats with a 1.82 cm.2 patch of left colon from which the mucosa had been stripped. The serosal surface was used as lining for the enterocystoplasty. The intestinal patch and the bladder capacity at known pressure were measured at operation and at sacrifice. The histology of the enterocystoplasty was studied in detail following sacrifice. Of the animals 40 survived without significant complications and were sacrificed at a mean postoperative time of 30 days (range 5 to 80 days). In the remaining 11 rats a bladder stone developed but it did not seem to affect the outcome of the experiment. The size of the patch could be measured in 22 rats: it was 1.82 cm.2 (standard deviation +/- 0.86) at operation and 2.30 cm.2 (standard deviation +/- 1.1) at sacrifice. In none of the rats did the patch decrease in size. The bladder capacity at a known pressure (mean 17 cm. water) could be measured in 26 animals: it was 2.35 ml. (standard deviation +/- 0.65) at operation and 5.18 ml. (standard deviation +/- 1.19) at sacrifice. Histological analysis was done in 40 rats. In all cases the serosal surface was lined with transitional epithelium, there was no fibrosis or inflammation and the structure of the muscular layer of the bowel remained intact. The earliest growth of uroepithelium in the serosal surface of the bowel was noted at 5 days. This model suggests that the seromuscular enterocystoplasty can be constructed successfully in the rat model. The seromuscular intestinal patch does not shrink. The bladder capacity increases and histology shows a uroepithelial lining of the augmentation. PMID- 1861301 TI - Bladder augmentation in patients with neurogenic bladder and vesicoureteral reflux. AB - Current treatment of noncompliant neurogenic bladder associated with significant vesicoureteral reflux that is refractory to intermittent self-catheterization and anticholinergic therapy includes bladder augmentation coupled with a procedure to eliminate reflux. Antireflux surgery is often difficult in such a clinical setting. The diseased and thickened detrusor makes reimplantation into the bladder difficult, and successful reimplantation into the intestinal component is tricky and time-consuming. Augmentation alone was done in 14 patients with significant vesicoureteral reflux in the face of a noncompliant, high pressure neurogenic bladder. No effort was made to correct reflux surgically because, in theory, reflux is secondary to abnormal bladder pressure. Of the 13 patients who have had adequate evaluation with postoperative cystograms 12 no longer have reflux. The reflux in the remaining patient has improved from grade IV to grade II. Postoperative cystometric examination in 12 patients demonstrated low pressure and adequate volume. Correction of bladder dynamics alone reversed the reflux. Conversely, persistence of reflux postoperatively is an indication that augmentation has not successfully returned the bladder to a low pressure reservoir. Our experience indicates that antireflux procedures are not routinely needed in this group of patients. PMID- 1861302 TI - Intraoperative cardiovascular collapse secondary to latex allergy. AB - An apparent allergic reaction has been noted in children undergoing open urological surgery. This condition is characterized by precipitous hypotension, tachycardia and upper body flushing, and it often causes termination of the procedure. Latex allergy has been identified as the possible inciting event. Contact of latex rubber gloves with intra-abdominal structures (handling bowel) appears to be the most dramatic trigger mechanism for this reaction. We report on 10 patients with latex allergy, 6 of whom have myelomeningocele, who have undergone reconstructive surgery. Severe anaphylactic shock developed intraoperatively in 5 patients and during a barium enema performed with a latex catheter in 1 patient. These 6 patients had previous allergic reactions to latex material, which was not detected preoperatively. In the remaining 4 patients latex allergy was diagnosed preoperatively. A total of 6 patients agreed to a skin prick test to liquid latex. Three patients reacted with a wheal size greater than or equal to a histamine control at a dilution of 1:1,000 and 3 patients at 1:100. In contrast, none of the 5 normal controls reacted to any of the concentrations including full strength latex. A history of exposure to latex products (balloons, surgical gloves, catheters, condoms and so forth) with allergic reactions should heighten surgeon awareness of a potentially severe intraoperative reaction. Furthermore, a skin prick test may be used to screen high risk patients such as those with myelomeningocele. A protocol involving preoperative corticosteroid and antihistamine therapy is recommended. PMID- 1861303 TI - Rubber-specific IgE in children with spina bifida. AB - We attempted to determine the prevalence and clinical significance of rubber specific IgE in a prospective case control study of 32 preoperative children with spina bifida, compared with 45 outpatient controls and 35 age-matched preoperative controls without spina bifida. A latex-specific radioallergosorbent test was positive in 11 of the 32 spina bifida patients (34%), compared with 1 (2%) and 4 (11%) of the respective controls (p less than 0.05). Within the spina bifida group 5 of 11 antibody-positive patients had a history of rubber associated, intraoperative or otherwise idiopathic allergic episodes and 1 of 21 antibody-negative patients gave such a history (p = 0.012). Children with spina bifida have a significantly greater likelihood than controls of having IgE specific for rubber antigens. In addition, the presence of rubber-specific IgE is associated with a higher frequency of rubber-associated, intraoperative or idiopathic allergic reactions. PMID- 1861304 TI - Cystic adrenal masses in the neonate associated with hemihypertrophy and the relation to the Beckwith-Wiedemann syndrome. AB - We report 2 cases of unilateral, multilocular, cystic adrenal masses in neonates. Both patients demonstrated somatic hemihypertrophy, which is considered to have the same implications as the Beckwith-Wiedemann syndrome in terms of tumor risk. Pathological examination showed multiple, adrenal cysts without evidence of tumor or routine adrenal hemorrhage. This finding appears to represent a previously unreported association between the spectrum of hemihypertrophy/Beckwith-Wiedemann syndrome and benign cystic adrenal disease. PMID- 1861305 TI - Abdominal cerebrospinal fluid pseudocyst: occurrence after intraperitoneal urological surgery in children with ventriculoperitoneal shunts. AB - Increasingly, children with ventriculoperitoneal shunts are undergoing urinary tract reconstructive surgery with bowel. The peritoneal end of the ventriculoperitoneal shunt tubing usually is exposed during the procedure, making the system vulnerable to infections and malfunction. The records of 103 myelomeningocele children with ventriculoperitoneal shunts and bowel-bladder reconstructive surgical procedures (27) were reviewed for evidence of an abdominal cerebrospinal fluid pseudocyst (6). Pseudocyst formation occurred in only 1 of 76 ventriculoperitoneal shunt patients (1.3%) who had not undergone versus 6 of 27 (22%) who had undergone an intra-abdominal procedure. The 6 children had a total of 8 pseudocysts, including 7 pseudocysts that developed 8 days to 47 months (average 15.1 months) after the reconstructive surgery and 1 that developed before reconstructive surgery. All patients had abdominal symptoms (pain or mass) or symptoms of increased intracranial pressure. Treatment included computerized tomography-guided needle aspiration or abdominal exploration with cyst evacuation and shunt repositioning or replacement. The walls of the pseudocyst were formed by matted loops of bowel. Additional shunt surgery was required in 5 patients with conversion to ventriculoatrial shunts. We conclude that the development of an abdominal cerebrospinal fluid pseudocyst is at least in part related to the prior abdominal surgery. Thus, pediatric urological and general surgeons caring for children with ventriculoperitoneal shunts should be aware of this complication. PMID- 1861306 TI - Sequential renography and renal function in Brown-Norway rats with congenital hydronephrosis. AB - Animal models may be helpful to gain insight into the long-term functional outcome of the hydronephrotic kidney. Inbred Brown-Norway rats frequently have kidneys with a delayed urine outflow. In 26 male rats 99mtechnetium diethylenetriaminepentaacetic acid (Tc-DTPA) furosemide renography was performed to assess the presence and degree of obstruction, and the contribution of each kidney to the total glomerular filtration rate. The total glomerular filtration rate was measured as the plasma clearance of 51chromium ethylenediaminetetraacetic acid. The measurements were first done at the age of 3 months, and repeated at ages 6, 10 and 15 months. From the renography curve we derived an obstruction score ranging from 0 (minimum) to 10 (maximum) based on the time to peak, the 99mTc-DTPA accumulation at 15 minutes and the furosemide response. Kidneys were classified as normal, obstructed or equivocal. At the first renography 21 kidneys were normal, 8 were equivocal and 23 were obstructed. The total obstruction score of the next 3 renographies indicated that 29 units were normal, 14 were equivocal and 9 were obstructed. Two groups of rats with unilateral hydronephrosis (hydronephrotic kidney-1 and hydronephrotic kidney-2) were selected based on the total obstruction score of all 4 renographies. These groups were compared with rats with 2 normal kidneys. The hydronephrotic kidney-1 rats had an obstruction score indicating equivocal obstruction, while the obstruction score of the hydronephrotic kidney-2 rats indicated obstruction. During the 15 months of followup the presence of a unilateral hydronephrotic kidney with an obstruction score indicating obstruction did not affect the contribution of the hydronephrotic kidney to the total glomerular filtration rate, or the total glomerular filtration rate. We conclude that the obstruction score of a hydronephrotic kidney in rats may change considerably with time. In cases in which renography suggested the permanent presence of ureteral obstruction the glomerular filtration rate remained stable. Thus, renal functional criteria did not indicate obstruction. In Brown-Norway rats a hydronephrotic kidney is able to maintain a normal glomerular filtration rate during at least 50% of the normal lfie span. PMID- 1861307 TI - The effect of urinary flow and bladder fullness on renal pelvic pressure in a rat model. AB - We describe an in vivo animal model used to study the interactions of urinary flow, and bladder pressure and fullness on renal pelvic pressure. These parameters were examined in 17 nonrefluxing Sprague-Dawley rats. At urinary flow rates less than 14 cc/kg. per hour and bladders less than 60% full, renal pelvic pressures were below 9 cm. water but at urinary flow rates more than 30 cc/kg. per hour renal pelvic pressure increased above 10 cm. water when the bladder was only 20% full. At all urinary flow rates examined renal pelvic pressure increased to more than 20 cm. water as the bladder approached 100% fullness. To quantitate the combined effects of these changes in renal pelvic pressure and urinary flow on the renal pelvis a renal pelvic work index (renal pelvic pressure times urinary flow rate) was defined. Using this index the magnitude of the change between low urinary flows with an empty bladder and high urinary flows with a full bladder can be observed. The results of these studies in this model might be applicable to high urinary flow states or bladders that fail to empty completely. PMID- 1861308 TI - The role of the kidney in lung growth and maturation in the setting of obstructive uropathy and oligohydramnios. AB - The contribution of the kidneys to lung development, which includes growth and maturation, is uncertain but it appears to be complex. Obstructive uropathy with oligohydramnios produces pulmonary hypoplasia characterized by small lungs (decreased lung volume/body weight) and retarded maturation (reduced total airspace). Lung growth and maturation were studied in a model of early gestation obstructive uropathy to understand better their relationship and their prenatal regulation. Of 26 fetal sheep studied at near term (135 days of gestation) 9 had bladder obstruction created at 60 days of gestation, 11 had bladder obstruction at 60 days with in utero decompression at 95 days, and 6 served as controls and shams. Amniotic fluid volume was measured, kidneys were prepared and evaluated histologically, lungs were inflation-fixed and volumes were measured, and airspace volume percentage was measured morphometrically. Experimental and serendipitous variations in the condition of the kidneys and amniotic fluid at delivery permitted an analysis of the contribution of the kidneys and the amniotic fluid to lung growth and maturation. Impairment of growth and maturation was dissociated in certain animals, and this dissociation was referable to the histological status of the kidneys and the presence or absence of amniotic fluid at delivery. Growth was normal when amniotic fluid was present or likely to have been present in late gestation, even with structurally damaged kidneys. With severe renal damage amniotic fluid was not restored even with in utero decompression and it resulted in severely impaired lung growth. Maturation was normal only in the presence of amniotic fluid and intact kidneys. The dissociation of lung growth and structural maturity suggests their independent regulation. The data suggest that the kidneys are important in early lung growth, while the presence of amniotic fluid contributes to growth later in gestation. Lung maturity requires both factors, suggesting a primary kidney contribution with the amniotic fluid acting in a permissive or supportive role. PMID- 1861309 TI - Radionuclide diuresis pyelography. AB - Radionuclide diuresis renography continues to be relied upon as a major diagnostic tool to differentiate obstructive and nonobstructive hydronephrosis. Controversy continues to exist with respect to methodology and interpretation of intermediate obstructive patterns. In this study radionuclide diuresis pyelography was performed in 11 renal units with hydronephrosis and a pre existing percutaneous nephrostomy tube in place. The procedure consisted of the introduction per kidney of 20 muc./kg. 99mtechnetium diethylenetriaminepentaacetic acid and sterile saline as a bolus into the renal pelvis via a percutaneous nephrostomy tube to produce a volume equal to the capacity of the hydronephrotic system. The kidney was monitored with a gamma camera and computer system. Furosemide (0.3 mg./kg.) was injected intravenously halfway into a 40-minute study. The time/activity curves thus generated were relatively independent of the cortical transport phase. The 2 types of curves were accelerated and constant. Analysis of these pyelogram curves revealed a strong correlation between the presence of an accelerated clearance rate response to furosemide and hydronephrosis without obstruction in 5 of 6 renal units. A constant clearance rate response to furosemide correlated with the presence of obstruction in 4 of 5 units. These observations may indicate that diuretic pyelogram curve dynamics may reflect not only the presence or absence of obstruction but also the ability of the hydronephrotic kidney to respond to the diuretic. More experience must be accumulated to determine the conditions under which diuresis pyelography may become useful clinically. PMID- 1861310 TI - Diuretic Doppler sonography in postnatal hydronephrosis. AB - Renal resistive indexes were measured by Doppler sonography in 12 children undergoing other standard diagnostic studies to evaluate hydronephrosis. Measurement of renal resistive indexes was modified by prior placement of a bladder catheter, oral hydration and administration of 1 mg./kg. furosemide after baseline measurement. Renal resistive indexes were again measured at 10 and 30 minutes after diuretic. While diuretic administration had no measurable influence on 10 nonobstructed kidneys, the elevated 10-minute post-diuretic renal resistive indexes recorded in 10 obstructed kidneys differed significantly from the indexes recorded in the nonobstructed group (p less than 0.001). The highest elevations in renal resistive indexes were recorded in nonpaired kidneys, which included 7 of the 10 kidneys in the obstructed group. In the 3 unilaterally obstructed kidneys the 10-minute post-diuretic renal resistive indexes did not differ significantly. However, renal resistive indexes in these kidneys increased at least 15% over baseline readings after diuretic administration. Diuretic Doppler sonography appears to be another useful method for differentiating functionally significant hydronephrosis from nonobstructive hydronephrosis in children. PMID- 1861311 TI - Management of the failed exstrophy closure. AB - In the last 5 years we have seen 15 boys and 9 girls with failure of exstrophy closure, including 20 who had classical bladder exstrophy and 4 who had cloacal exstrophy. At the time of presentation 18 patients had undergone 1 closure while 6 patients had undergone 2 prior exstrophy closures. Closure was performed for complete bladder dehiscence in 16 cases and for significant bladder prolapse in 8. None of the patients underwent any form of osteotomy at the time of initial closure and in 19 closure was done within 72 hours of birth. Two patients underwent posterior iliac osteotomy elsewhere at the time of secondary closure. All patients referred to our institution underwent either posterior iliac osteotomy (8 patients) or anterior innominate osteotomy (16 patients). Epispadias repair along with reclosure of bladder exstrophy was done in 13 boys. The upper tract remained normal in all patients. There were no instances of failure in this group of reclosures. Eight patients have undergone subsequent bladder neck reconstruction of whom 7 are dry for 4 hours and 1 remains totally incontinent. Two patients have undergone simultaneous bladder neck reconstruction and augmentation cystoplasty, and they are dry on intermittent self-catheterization. The failed exstrophy closure presents a formidable dilemma. However, a secure reclosure can be achieved with careful surgical technique, a well performed osteotomy (even if previously performed) and concomitant epispadias repair for male subjects. PMID- 1861312 TI - Vesical neck reconstruction in patients with epispadias-exstrophy complex. AB - The achievement of satisfactory continence in the management of patients with the epispadias-exstrophy complex remains a challenge. Between 1971 and 1989, 22 children underwent vesical neck reconstruction at our hospital. Satisfactory continence was achieved in 17 of the 22 patients (77%), including 8 (36%) who are continent after a single vesical neck reconstruction and 9 of 13 who achieved continence after additional and/or adjunctive procedures. Additions and/or adjunctive procedures included revision of the vesical neck reconstruction, bladder augmentation and/or placement of an artificial urinary sphincter. We conclude that vesical neck reconstruction with or without additional and/or adjunctive procedures can result in an acceptable continence rate in patients with the epispadias-exstrophy complex. PMID- 1861313 TI - Techniques to create urinary continence in the cloacal exstrophy patient. AB - Of 15 patients with cloacal exstrophy currently under management 11 have undergone procedures for the establishment of urinary continence. There were 8 genetic female subjects, 6 genetic male subjects raised as girls and 1 genetic male subject raised as a boy. The genetic female subjects had all undergone urethral reconstruction. In 4 patients urethral reconstruction was done with local tissues and they have subsequently undergone bladder neck reconstruction: 1 is continent and voids through the urethra, 2 are dry on intermittent catheterization and 1 is dry on intermittent catheterization after augmentation with a hindgut patch. One girl underwent a Kropp procedure along with bladder augmentation, and she is dry on intermittent catheterization, in 1 urethral reconstruction was done with an ileal nipple through which she performs intermittent catheterization and 2 await a continence procedure. The urethral reconstructions in the genetic male subjects were more difficult. Of the 6 genetic male subjects raised as girls 5 have undergone continence procedures and 1 awaits establishment of urinary continence. In only 1 patient was urethral reconstruction possible from local tissues to allow intermittent catheterization. In the other 4 the perineal urethra was closed in favor of an abdominal stoma for intermittent catheterization. Ileal plication with nipple formation of the stoma was done in 3 patients and a Benchekroun stoma was used in 1. The genetic male subject raised as a boy underwent exstrophy reclosure plus epispadias repair and subsequent bladder neck reconstruction and augmentation. Augmentation was performed in 5 patients with hindgut segments in 3 and ileum in 2. All 5 patients are currently dry on intermittent catheterization, although 1 required revision of the ileal nipple to a Benchekroun stoma. Staged reconstruction can produce acceptable urinary continence in this complex anomaly. An innovative approach is required to find the most suitable solution for each patient anatomy, bladder size and function, and mental, neurological and orthopedic status. PMID- 1861314 TI - Flow cytometry of fine needle aspirations of the Sprague-Dawley rat testis: defining normal maturation and the effects of multiple biopsies. AB - Quantitative assessment of spermatogenesis by flow cytometry reproducibly correlates with histological examination. Flow cytometry of fine needle aspirates from the testis was used to analyze normal spermatogenesis of Sprague-Dawley rats. Aged matched male weanlings were divided into 3 groups: group 1-5 rats underwent bilateral percutaneous aspiration of the testes with a 22 gauge Chiba needle on postpartum days 19, 24, 30 and 40; group 2-5 rats aspirated on days 24, 30 and 40, and group 3-4 rats aspirated on days 30 and 40. This sequential approach allowed for evaluation of normal spermatogenesis and the effects of repeated fine needle aspiration on spermatogenesis. Deoxyribonucleic acid distribution analysis by flow cytometry correlates with haploid (1N), diploid (2N), tetraploid (4N) and S phase cell populations. These cell populations were evaluated and comparisons among each group were made at all biopsy times. No significant differences in mean 2N, 4N or S phase cell populations in single versus repeat biopsied testes were detected. However, there was a significant increase in the 1N population at 30 days post partum in the repeat biopsy group (p = 0.037), which normalized by day 40. This increase in 1N corresponds to the beginning of meiosis, which is maximal between postpartum days 30 and 40, and occurs earlier in the repeat biopsied testis. Repeat fine needle aspiration of the testis can be performed without significantly affecting spermatogenesis in the "weanling" rat. This provides a useful technique in the future investigations of the time related effects of varicocele, chemotherapy and toxicologic drugs on spermatogenesis. PMID- 1861315 TI - Effectiveness of trigonoplasty to treat primary vesicoureteral reflux. AB - Among the surgical procedures to treat vesicoureteral reflux trigonoplasty is a conservative technique that preserves the integrity of the vesicoureteral junction. Since its introduction in 1984 by Gil Vernet it gained only little attention in small series. Between 1986 and 1989 we performed trigonoplasty in 51 children 4 months to 13 years old, of whom 47 had primary vesicoureteral reflux. Our study includes 44 patients who have sufficient followup and 69 refluxing units. Reflux was grade II in 25 units, grade III in 39 and grade IV in 5. Patients were arbitrarily divided into 2 age groups: less than (13) and greater than (31) 3 years old. All children underwent standard preoperative assessment. The operation, with technical modifications (absorbable sutures in all cases and muscular incision added in 12), was performed after failed conservative treatment in all patients except 5 who were operated on at diagnosis. Surgery was successful in 97.7% of the patients and in 92.3% of the children less than 3 years old. The only recurrence was noted on 1 side of a 2-year-old child who had had grade IV bilateral reflux. Considering that reimplantation threatens the integrity of the vesicoureteral junction and endoscopic injections still have unclear side effects, indications for trigonoplasty can be extended to higher grades of reflux if ureteral tapering is not required and a sufficient intramural length of ureter can be obtained. PMID- 1861316 TI - M inverted V glansplasty: a procedure for distal hypospadias. AB - Minimal hypospadias is a commonly encountered anomaly. Duckett's innovative meatoplasty and glanuloplasty (MAGPI) procedure has become a standard operation for the correction of these lesions. Although usually successful, the complication of meatal retraction has been recognized at times after a MAGPI. The M inverted V glansplasty was designed to address the factors leading to meatal retraction and the abnormal glans shape sometimes seen after the MAGPI. The M inverted V glansplasty derives its name from the initial M-shaped incision that reconfigures during the course of the procedure into an inverted V. Of 16 boys followed for more than 2 months after an M inverted V glansplasty 14 have achieved good results. The remaining 2 cases had a definite degree of meatal retraction but because of the meatal and glanular relationships they have a good cosmetic result. The technique, its indications and its limitations are described. PMID- 1861317 TI - Distal hypospadias repair by urethral sliding advancement and Y-V glanuloplasty. AB - Different techniques are available today for repairing distal (coronal and subcoronal) hypospadias but none is universally recommended. We developed the technique of a distal urethral advancement glanuloplasty operation that is specifically intended for distal hypospadias repair even with mild chordee. Mobilization of the distal urethra is performed for 1.0 to 1.5 cm. after subcoronal circumcision and a deep Y-shaped incision of the glans. The mobilized urethra is dorsally split and slid forward to the tip of the dart of the glans previously prepared. Glanuloplasty is performed using the 2 lateral flaps of glans tissue. From January 1987 to December 1989 we used this technique in 74 cases of distal hypospadias with mild or no chordee (patient age 18 months to 9 years, mean 3.5 years). A transurethral catheter was left indwelling for 3 to 4 days. Hospitalization time was 5 (plus or minus 1.5) days. Results after 4 to 40 months of followup are encouraging cosmetically and functionally. All patients were cured. In 3 cases (4%) meatal stenoses occurred requiring meatotomy and in 8 boys meatal dilations were performed on an outpatient basis. In 1 case (1.3%) a fistula developed, which was subsequently repaired without further complications. This operation may be successfully used in most cases of distal hypospadias, with a low complication rate and excellent cosmetic results. It also may be used if mild chordee is present, thus reducing the indications for flip-flap urethroplasty in those cases when meatal advancement procedures may not be effective. PMID- 1861318 TI - Abdominoperitoneal approach to management of the high, short vagina in the adrenogenital syndrome. AB - We describe a combined transtrigonal, abdominoperineal approach to the surgical management of the female pseudohermaphrodite with the adrenogenital syndrome and a high, short vagina. Most of our patients had undergone previous clitoral reduction surgery and, therefore, clitoral shaft skin was not available for exteriorization of the vagina. Our operation involves partial mobilization of the vagina through an inverted U flap from the perineum followed by detachment from the urogenital sinus from above by splitting the trigone. Exteriorization is accomplished by mobilizing 2 lateral skin flaps from the perineum and joining them with the inverted U flap to reach the vagina. Cosmetic results have been excellent, although anastomotic stenosis occurred in 1 young infant. PMID- 1861319 TI - Renal blood flow measurements using radioactive microspheres in a porcine model with unilateral vesicoureteral reflux. AB - Renal blood flow was studied in Yorkshire pigs with surgically created unilateral vesicoureteral reflux using radionuclide labeled microspheres. The contralateral, nonrefluxing kidney served as a within-subject control and a group of nonoperated pigs without reflux served as an additional control group. Unilateral reflux did not change the distribution of whole renal blood flow between the refluxing and nonrefluxing kidneys. In addition, reflux had only minor effects upon the distribution of blood flow to cortical regions within the kidneys. PMID- 1861320 TI - Urinary levels of renal tubular enzyme N-acetyl-beta-D-glucosaminidase in relation to grade of vesicoureteral reflux. AB - Elevated urinary levels of the renal tubular enzyme N-acetyl-beta-D glucosaminidase (NAG) have been shown to be associated with tubular damage. To determine whether urinary levels of NAG would be abnormal and/or vary with the severity of vesicoureteral reflux, bladder urine was obtained from 31 children without reflux and 32 children with various grades of reflux. Nonrefluxing controls were obtained from children undergoing evaluation for a history of infection, hematuria or voiding abnormality. Patients with evidence of obstruction, neuropathic bladder dysfunction, urinary tract infection or renal failure were excluded. Bladder (32 cases) and ureteral (5 cases) urine from children with reflux was obtained at cystography or at antireflux surgery. Control and reflux patients were not significantly different with regard to sex or age. The mean urinary NAG level in nonrefluxing control patients was 10.63 IU/mg. (range 0.94 to 26.61, standard error of mean 0.43). Mean urinary NAG for all patients with reflux was 16.47 IU/mg. (range 2.85 to 52.02, standard error of mean 0.9). Two children with intrarenal reflux had urinary NAG levels of 52 and 48 IU/mg. Urinary NAG levels are elevated with higher grades of reflux and this relatively simple assay may have clinical usefulness in the assessment of tubular dysfunction associated with reflux. PMID- 1861321 TI - Duplex reflux: a study of 105 children. AB - A series of 105 children with vesicoureteral reflux into completely duplicated collecting systems was studied retrospectively. Of the children 64% were treated surgically, with two-thirds undergoing an ablative procedure and one-third undergoing common sheath ureteral reimplantation. The remaining 36% of the children were managed nonoperatively and followed for up to 11 years. Among these cases 89% of the kidneys had reflux into the lower pole moiety only and 11% had reflux into the upper and lower pole moieties. The spontaneous rates of reflux resolution were 85% for grades I and II, and 36% for grade III reflux during a median observation period of 40 months. These figures suggest that the spontaneous resolution of mild to moderate reflux into completely duplicated collecting systems is similar to that of identical degrees of single system reflux during a comparable observational period. PMID- 1861322 TI - Reflections on 30 years of treating children with urinary tract infections. PMID- 1861323 TI - Failure of motor evoked potentials to predict neurologic outcome in experimental thoracic aortic occlusion. AB - Motor evoked potential monitoring was tested as an alternative to somatosensory evoked potential monitoring in evaluating spinal cord function during thoracic aortic occlusion in dogs. Twenty-seven animals underwent 60 minutes of cross clamping of the proximal descending thoracic aorta with (n = 18) or without (n = 9) cerebrospinal fluid drainage. Spinal cord blood flow was measured with microspheres, and neurologic outcome was evaluated at 24 hours with Tarlov's scoring system. Cerebrospinal fluid drainage improved neurologic outcome (p less than 0.05). Motor evoked potentials recorded over the lumbar spinal cord were lost in 9 of 20 dogs with ischemic cord injury and were not lost in any of the 7 dogs that were neurologically normal. Somatosensory evoked potential were lost in 19 of 20 paraplegic/paraparetic dogs and lost in 3 of 7 normal dogs (p less than 0.01). After reperfusion, motor evoked potentials returned in all nine neurologically injured dogs that lost the potentials and were still present at 24 hours. Changes in amplitude, latency, or time until loss or return of motor evoked potentials or somatosensory evoked potentials did not predict neurologic injury. Loss of somatosensory evoked potentials had a high sensitivity (95%) but had low specificity (67%) because of peripheral nerve ischemia. Loss of motor evoked potentials recorded from the spinal cord had high specificity (100%) but a low sensitivity (46%) and was therefore not a reliable predictor of neurologic injury. Return of motor evoked potentials during reperfusion did not correlate with functional recovery. Motor evoked potentials stimulated in the cortex and recorded from the spinal cord had low overall accuracy (59%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861324 TI - Quantification of vascular graft seeding by use of computer-assisted image analysis and genetically modified endothelial cells. AB - Current methods for the evaluation of retention of endothelial cells seeded on vascular grafts are limited by the inability to specifically identify and quantitate seeded cells on a long-term basis. To address this problem we developed a method of quantification of graft surface coverage using genetic labeling of endothelial cells combined with computer-assisted image analysis. Rabbit aortic endothelial cells were transduced with a marker gene (lac-Z) and seeded on polytetrafluoroethylene grafts. After histochemical staining in which the genetically labeled cells turn blue, computer-assisted image analysis was used to measure the percentage of graft surface covered by the seeded cells. The utility of the method was evaluated by using it to assess the effect on graft coverage of seeded cell density and by precoating with fibronectin. Quantification of surface area coverage was automated and reproducible both between scans and between observers. Use of this method allowed the determination of a linear correlation between cell density in the seeding suspension and graft coverage (r2 = 0.93, p less than 0.0001). The method also permitted confirmation of the positive contribution of fibronectin coating to graft coverage by seeded cells: 73% coverage coated versus 8% coverage uncoated (p less than 0.0001). The ability of this method to specifically identify genetically marked endothelial cells and their progeny makes it attractive for use in studies targeted at optimization of graft coverage in vivo. PMID- 1861325 TI - Thermal laser-assisted balloon angioplasty of the superficial femoral artery: a multicenter review of 602 cases. AB - A multicenter review of 602 procedures was performed to evaluate the effects of thermal laser-assisted balloon angioplasty on the superficial femoral artery. Four hundred thirty-nine (73%) patients underwent laser-assisted balloon angioplasty for claudication, and 163 (27%) underwent the procedure for limb salvage. Two hundred ninety-two laser-assisted balloon angioplasty procedures were performed for multifocal stenotic disease (greater than 80%) diameter reduction), 258 for total occlusion, and 52 procedures for both superficial femoral artery stenosis and occlusion. The initial recanalization rate was 89% (538/602) depending on the length of the lesion. Success of laser-assisted balloon angioplasty was verified by angioscopy or arteriography, and all patients underwent segmental Doppler studies before discharge and during midterm follow-up extending to 30 months (mean, 11.3 months). Complications occurred in 62 (10%) patients, but only one limb amputation occurred because of a complication related to a laser-assisted balloon angioplasty. Overall, 60% of initially successful procedures have remained patent, but long segment (greater than 7 cm) occlusions have fared poorly (25% patency at 30 months). This minimally invasive technology affords the opportunity to treat short segment (less than 7 cm) symptomatic superficial femoral artery occlusive disease with minimal risk. Initial success and midterm patency rates for appropriate lesions appear to make laser-assisted balloon angioplasty a viable adjunct in the treatment of superficial femoral artery occlusive disease. PMID- 1861326 TI - Multivariate clinical models and quantitative dipyridamole-thallium imaging to predict cardiac morbidity and death after vascular reconstruction. AB - Patients with peripheral vascular disease have a high prevalence of coronary artery disease and are at increased risk for cardiac morbidity and death after vascular reconstruction. The present study was undertaken to assess the value of 18 clinical parameters, of 7 clinical scoring systems, and of quantitative dipyridamole-thallium imaging for predicting the occurrence of postoperative myocardial infarction or cardiac death. Vascular surgery was performed in 125 patients. Thirteen postoperative cardiac events occurred, including 10 cardiac deaths and 3 nonfatal infarctions. Clinical parameters were not useful in predicting postoperative outcome. All 63 patients with normal scan results or fixed perfusion defects underwent surgery uneventfully, whereas 21% (13/62) of patients with reversible defects had a postoperative cardiac complication. By use of quantitative scintigraphic indexes we found that patients with reversible defects could be stratified into intermediate and high-risk subgroups with postoperative event rates of 5% (2/47) and 85% (11/13), respectively, despite intensive postoperative monitoring and antianginal medication. Thus in patients unable to complete a standard exercise stress test, postoperative outcome cannot be predicted clinically, whereas dipyridamole-thallium imaging successfully identified all patients who had a postoperative cardiac event. By use of quantification we found that patients with reversible defects can be stratified into an intermediate risk subgroup that can undergo surgery with minimal complication rate and a high-risk subgroup that requires coronary angiography. PMID- 1861327 TI - Septic complications after cardiac catheterization and percutaneous transluminal coronary angioplasty. AB - Septic complications after cardiac catheterization and percutaneous transluminal coronary artery angioplasty are distinctly uncommon. However, we have recently treated nine patients with sepsis and life-threatening complications after cardiac catheterization alone or after catheterization and subsequent percutaneous transluminal coronary angioplasty. The common denominator in all patients was either repeat puncturing of the ipsilateral femoral artery or leaving the femoral artery sheath in for 1 to 5 days after the procedure. Two patients died as a direct result of their septic complications. One death occurred in a patient in whom bacterial endocarditis with congestive heart failure developed, and the other patient had a large retroperitoneal hematoma that became secondarily infected. Infected aneurysms that were successfully treated developed in three patients. Our study suggests that colonization of the needle tract by skin flora predisposes to septic complications if repeat arterial punctures are required or if a femoral artery sheath is left in place for more than 24 hours. Patients in whom sepsis develops after these procedures should be initially treated with antibiotics effective against gram-positive organisms. CT scanning or angiography should be considered for patients with persistent sepsis, septic emboli, and abdominal or flank pain. Infected aneurysms require resection or ligation because of the propensity of these aneurysms to rupture. PMID- 1861328 TI - Transverse versus longitudinal arteriotomy: an experimental study in dogs. AB - An arteriotomy is a commonly used surgical technique. Either a transverse or a longitudinal incision can be made, but no study has been done to determine if one technique results in more stenosis or flow disturbance than the other. Six millimeter arteriotomies were made on the carotid and femoral arteries of six dogs. Transverse arteriotomies were made on the right, and longitudinal arteriotomies were made on the left. Four weeks later the vessels were reexplored. Duplex scanning was used to assess the amount of turbulence at each arteriotomy. Afterward, latex casts of the arteries were made to determine the percent stenosis caused by each arteriotomy. The mean percent stenosis associated with transverse arteriotomies was 10.5% (+/- 4.4%), versus 22.8% (+/- 9.4%) for the longitudinal arteriotomies, (p = 0.001, matched t test). No difference in the amount of turbulence associated with each technique was demonstrated. A longitudinal arteriotomy results in significantly greater stenosis than does a transverse arteriotomy. Unless there is a specific indication for a longitudinal arteriotomy, a transverse arteriotomy should be used. PMID- 1861329 TI - A comparison of absorbable suture and argon laser welding for lateral repair of arteries. AB - Conventional vascular anastomoses between autogenous vessels are performed with nonabsorbable sutures. Recently, use of absorbable sutures and laser-assisted vascular anastomoses has been advocated because of their improved healing characteristics. This study compared arterial repairs with the argon laser, absorbable suture, and nonabsorbable suture for technical characteristics including additional suture and overall success rates, burst strength, and cost. Absorbable and nonabsorbable suture closures were comparable with respect to technique, but laser-assisted vascular anastomosis was technically more demanding and required almost twice as much time for completion. The argon laser successfully closed only 58.6% of the arteriotomies, and 90% of the closures required additional sutures for complete hemostasis. All sutured arteriotomies were successfully completed by use of either absorbable or nonabsorbable suture. Burst strength was similar for all groups, but was uniformly greater than 300 mm Hg for sutured repairs, whereas two of five laser-assisted closures burst below 300 mm Hg. Finally, costs for purchasing ($35,000) and operating ($300/hr.) an argon laser make laser-assisted vascular anastomosis much more expensive than sutured repair. These data suggest argon laser-assisted vascular anastomoses are more technically demanding, less successful, and more expensive than conventional sutured anastomoses when evaluated in large caliber arteries in a canine model. Absorbable suture, however, is comparable to conventional nonabsorbable sutured arterial repairs in expense, handling characteristics, and success rates with the added advantage of eliminating permanent foreign body in the arterial wall when it is absorbed. PMID- 1861330 TI - The risk of axillofemoral bypass grafting for acute vascular occlusion. AB - The hypothesis of the present study is that axillofemoral bypass grafting for acute vascular occlusion has results significantly inferior to an elective procedure. We reviewed 53 patients undergoing primary axillofemoral bypass grafting at the University of Virginia from 1984 to 1989. We found that patients who were admitted with acute vascular occlusion had a higher incidence of perioperative complications (63% vs 26%, p = 0.001), perioperative mortality (26% vs 3%, p less than 0.05), lower graft patency at 1 year (60% vs 90%, p less than 0.05), lower rate of freedom from reoperation in first year (50% vs 82%, p less than 0.01), and lower rates of limb salvage (76% vs 94%, p less than 0.05) than patients undergoing axillofemoral bypass grafting for chronic symptoms or conditions. These two groups did not differ in any of the other risk factors or perioperative characteristics examined. We conclude axillofemoral bypass grafting performed for indications other than acute vascular occlusion is associated with acceptable morbidity, mortality, graft patency, and limb salvage rates. PMID- 1861331 TI - Asymptomatic celiac and superior mesenteric artery stenoses are more prevalent among patients with unsuspected renal artery stenoses. AB - The prevalence of unsuspected renal artery stenosis among patients with peripheral vascular disease has been reported to be as high as 40%, but the prevalence of asymptomatic celiac and superior mesenteric artery stenoses in these patients is not known. The biplane aortograms of 205 male patients who were military veterans and had aneurysms or occlusive disease were independently reviewed, and medical records were studied to determine associated coronary disease, risk factors, and patient outcome. Fifty-six patients (27%) had a 50% or greater stenosis in the celiac or superior mesenteric artery, and seven patients (3.4%) had significant stenoses in both mesenteric arteries. Patients with celiac or superior mesenteric artery stenoses were older (p = 0.002) and had a higher prevalence of hypertension (p = 0.029) than those without significant mesenteric stenoses. Fifty of the 205 patients had significant renal artery stenoses, and 20 had advanced (greater than 75% diameter loss) renal stenoses. Ten of the 20 patients (50%) with advanced renal stenoses had a concomitant celiac artery stenosis, compared to 40 of the 185 patients (22%) who did not have advanced renal stenoses (p = 0.011). In the present study asymptomatic celiac or superior mesenteric artery stenoses were common among male veterans evaluated for peripheral vascular disease, but the prevalence of significant stenoses in both the celiac and superior mesenteric arteries was low. The prevalence of significant celiac stenosis was higher in patients with advanced (greater than 75%) renal artery stenoses who might be considered for prophylactic renal revascularization. Lateral aortography with evaluation of the celiac artery is always appropriate in these patients. PMID- 1861332 TI - Renovascular hypertension: predicting surgical cure with exercise renography. AB - Renal artery stenosis with resultant renovascular hypertension has attracted clinical attention because the disease is potentially curable and because numerous diagnostic and therapeutic modalities compete for clinical acceptance. An exercise-mediated disturbance of renal hippurate transport was recently described, and has been implicated as having a role in nephrogenic fixed hypertension. To predict the final course of renovascular hypertension before operation we carried out a prospective study with the goal of verifying the predictive value of exercise hippurate scintigraphy. The study was to test the hypothesis that patients with disturbance of renal hippurate transport (pathologic renogram) induced by exercise would have stabilized hypertension and would continue to be hypertensive after operation. Thirty-one patients with hypertension who had unilateral or bilateral renovascular stenosis documented on angiography were referred to rest and exercise hippurate scintigrams before operation. The results of the examinations at rest served as standard and were compared with the exercise scintigrams. In 19 of the 31 (61%) patients a disturbance of transrenal hippurate transport evolved during exercise, whereas 12 (39%) patients failed to respond to exercise with altered hippurate kinetics. Twenty-six patients went on to renovascular operations; five had percutaneous transluminal angioplasty. Revascularization results differed markedly when the blood pressure response of patients with positive results on exercise (abnormal) and patients with negative results on exercise (normal) were compared. Ten of 12 patients with hypertension who had normal exercise renograms were cured. In comparison, blood pressure values were little influenced by therapy in patients with an abnormal response, where 17 of 19 patients continued to have hypertensive disease after therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861333 TI - Mycotic aneurysms of the carotid arteries--case report and review of the literature. AB - Mycotic aneurysms of the extracranial carotid arteries are rare. We report a new case with a mycotic aneurysm of the carotid bifurcation associated with acute bacterial endocarditis of the aortic valve. A concomitant treatment of both lesions was performed. Twenty-six cases of mycotic aneurysms of the extracranial carotid arteries have been reported in the literature. We present a review of all these cases. PMID- 1861335 TI - Digital artery embolization as a result of fibromuscular dysplasia of the brachial artery. AB - A 74-year-old woman was admitted to the hospital with sudden onset of a blue, painful right index finger, and the condition progressed to digital ulceration. The ulcer gradually healed over a period of 2 months. Peripheral pulses, Doppler derived brachial and radial systolic pressures, and results of an echocardiogram were normal. Digital pulse volume recordings showed obstructive waveforms in all digits of the right hand. Arteriography showed a normal arch and normal innominate, subclavian, and axillary arteries. The midbrachial artery was markedly abnormal and had alternating areas of stenosis and aneurysm formation. Multiple occlusions involved the palmar arch and proper digital arteries. The abnormal brachial artery segment was excised and replaced with an autogenous reversed saphenous-vein conduit. Histologic examination confirmed the lesion to be medial fibromuscular dysplasia. Fibromuscular dysplasia that involves upper extremity arteries is extremely uncommon and rarely presents with digital artery embolization. This case emphasizes the importance of exclusion of proximal reconstructible arterial occlusive disease by means of complete arteriographic examination of patients who were admitted with unilateral finger or hand ischemia. PMID- 1861334 TI - Peripheral arterial occlusion in infants--a report of two cases treated conservatively. AB - The occlusion of major arteries in newborns is usually associated with catheterization of the umbilical vessels. It occurs very rarely instead as a primary disorder, and the cause is still unclear. We present two new cases of newborns with this type of disease, which were resolved with the only medical treatment. The literature is reviewed, and the usefulness of the different diagnostic procedures is discussed. PMID- 1861336 TI - Thoracic outlet syndrome caused by tumor of the first rib. AB - We report a new case of thoracic outlet syndrome caused by a tumor of the first rib and review 11 other reports found in the literature. A 25-year-old man was admitted with thoracic outlet syndrome in the C8-T1 nerve roots. The first rib was removed through a supraclavicular approach with excision of the medial clavicle. All symptoms disappeared. On histologic examination fibrous dysplasia was found in the rib. Tumors of the first rib are uncommon and are rarely responsible for thoracic outlet syndrome. When the tumor is very large, as in our case, we recommend a supraclavicular approach associated with excision of the medial clavicle. During the liberation of the brachial plexus, great care should be exercised to avoid nerve injuries. Because malignancy of the tumor cannot be eliminated with certainty before or during the operation, wide excision of the entire rib is recommended. PMID- 1861337 TI - Postoperative surveillance and characteristics of failing infrainguinal grafts. PMID- 1861338 TI - Carotid patch angioplasty: immediate and long-term results. PMID- 1861340 TI - Diagnosis of giardiasis. PMID- 1861339 TI - An unusual symptom of subclavian artery aneurysm: hemoptysis. PMID- 1861341 TI - Giardia lamblia in patients undergoing upper G.I. endoscopy. AB - To determine the frequency of giardiasis in patients undergoing upper G.I. endoscopy for dyspepsia and other upper G.I. disorders, duodenal aspirates were collected in 200 patients and simultaneous duodenal biopsies in 163 patients. Nine percent aspirates and 1.8% duodenal biopsies showed Giardia lamblia trophozoites. Giardia as a cause of dyspepsia should be considered in patients with negative endoscopy and in those who remain symptomatic inspite of adequate treatment for known upper G.I. disorders. PMID- 1861343 TI - Haemolytic uraemic syndrome in children. AB - Of the 4070 children admitted in the department of paediatrics, 830 (24%) presented with diarrhoea. Eleven of these had haemolytic ureamic syndrome (HUS) characterised by microangiopathic haemolytic anaemia, thrombocytopenia and acute renal failure. Only 3 had positive stool cultures (E. Coli 2, shigella dysenteriae 1). Two children expired while the rest recovered with conservative management and peritoneal dialysis. Thus HUS should be remembered as a complication of diarrhoea and a cause of acute renal failure in children. PMID- 1861342 TI - Surveillance of shigellosis in rural Bangladesh: a 10 years review. AB - Over a period of 10 years 35,620 patients, admitted from a defined surveillance area, had a rectal swab culture done at a rural diarrhoea treatment centre in Bangladesh. Shigella spp. were isolated from 3,440 (9.7%) cases. Marked year to year variations were observed in isolation rates of Shigella spp. ranging from 5.7% to 16.7%. Sh. flexneri was the predominant isolate between 1978 to 1982 (56% 67%), Sh. dysenteriae type 1 predominated from 1983 to 1985 (45%-50%), and again Sh. flexneri became predominant in 1986 (55%) and 1987 (61%). Shigella were most commonly isolated from children aged 1-4 years followed by children 5-9 years and elderly people aged 45+ years. Sh. flexneri was isolated most frequently during August - January and Sh.dysenteriae type 1 during June to July. The overall case fatality rate in patients with shigellosis was 0.96%. It was 1.10% in children under 5 years of age. Prevalence of multiple antibiotic resistant strains increased over the years and at present most strains are resistant to commonly used antibiotics such as ampicillin and cotrimoxazole. Nalidixic acid is currently the drug of choice for Shigella infection in this area. PMID- 1861344 TI - Intraoperative myocardial ischaemia in surgical patients with treated ischaemic heart disease. AB - Twenty patients were divided into 2 groups. Group - A had 10 ASA Grade I while Group - B consisted of 10 asymptomatic patients with ECG evidence of ischaemia. One week of coronary dilator treatment was given to the patients in group-B before surgery. Intra operative cardioscopic monitoring was done in both the groups. In group-B, 5 patients showed ECG evidence of intraoperative myocardial ischaemia, and/or ventricular ectopics, which were in most cases attributable to anaesthetic/surgical stimuli but were not always associated with increased Rate pressure product. In group-A only one patient showed ECG evidence of ischaemia intraoperatively. It is therefore concluded that patients with optimal therapy for IHD continue to be at risk of intraoperative cardiovascular abnormalities. PMID- 1861345 TI - Minimum induction dose (MID) of thiopentone in Pakistani patients. AB - The thiopentone dose needed for abolition of eyelash reflex was studied in 505 Pakistani patients who were divided in three subgroups, i.e., age less than 16 years, between 16 and 60 years, and over 60 years. The minimum induction dose for thiopentone was then determined in the three groups and the effect of sex, ASA classification, premedication and advancing age were seen. The minimum induction dose in the adult patients (16-60) was 215.8 +/- 66 mgs (3.48 mgs/kg). Both the adult groups and the elderly showed a statistical difference in the dose required by the males and females, but this difference was not seen in children. Thiopentone dose also showed a steady decline as the age progressed. A statistical correlation existed between ASA I and II patients compared to ASA III who required less thiopentone. The premedicated patients required less thiopentone compared to those who did not receive a premedication. Our patients required a lesser dosage for abolition of eyelash reflex than the figures recommended for British population. We recommend a dose of 3.5 mg/kg for adult Pakistani males and 3.3 mg/kg for adult females. PMID- 1861347 TI - Gene and genotypic frequency and percent of bitter tasters of phenyl thiocarbamide in a student community of different castes. PMID- 1861346 TI - Histiocytic necrotizing lymphadenitis. A clinicopathological study. AB - Seven cases of Histiocytic necrotizing Lymphadenitis (HNL) were studied. They constituted 0.56% of all lymph nodes biopsies. The condition primarily affects young women causing cervical lymph node enlargement and leukopenia. The basic lesion is characterized by proliferation of lymphocytes and histiocytes with nuclear debris in the para cortex and cortex. This study examined various bacterial, viral and immunological factors which could possibly be responsible for this condition. However, it failed to find positive association with any of them. The existence of this disease in Pakistan is documented. PMID- 1861348 TI - An unusual case of ataxia. PMID- 1861349 TI - Selenium. PMID- 1861350 TI - Collection and handling of specimens for microbiological examination. PMID- 1861351 TI - Prevalence of premenstrual syndrome in Pakistani women. AB - The prevalence of premenstrual syndrome (PMS) was determined in 1600 women belonging to various socioeconomic groups in Karachi. Of the total, 33% had PMS, whose prevalence was high in lower socioeconomic group living in socially deprived areas. A direct association of PMS was noted with parity, being low in low parity group. Major complaints were pain in lower abdomen, cramps and backache with majority taking no treatment for their complaints. PMID- 1861352 TI - Can diagnosis of Helicobacter pylori be rapid and yet sensitive? AB - Diagnostic accuracy of 5 tests viz., endoscopy, rapid urease, 24 hours urease, culture and histology, were evaluated in the detection of Helicobacter pylori (H. pylori) infection in 50 patients undergoing upper G.I. endoscopy. Endoscopic evidence of gastritis to predict H. pylori infection was 50% specific and 46% sensitive. Rapid and 24 hours urease test and culture were 100% specific when compared with histology and their sensitivity was 71%, 62% and 21% respectively. Of the three 100% specific tests, rapid urease test yields results within 15 minutes; therefore this test being easy, rapid and sensitive should be used for screening of H. pylori infection; followed by histology for further confirmation. PMID- 1861353 TI - Post traumatic facial paralysis--a review. AB - A retrospective analysis of 23 cases of post-traumatic facial nerve injury has been done. Majority of the cases had a conductive or a mixed deafness. The Schirmer's test has been considered to be one of the main indicators to determine the site of injury. The mastoid segment of the facial nerve was found to be injured in 52% of the patients. The surgical approach in patients with post traumatic facial nerve paralysis should be transmastoid. This can be combined with a middle fossa approach in patients with a positive Schirmer's test. PMID- 1861354 TI - The effect of paracetamol on naprosyn induced damage to gastric mucosa in albino rat. AB - The effect of paracetamol against ulcerogenic agent, naprosyn on the gastric mucosa of albino rat was observed under dissecting as well as laboratory microscope. Paracetamol in a dose of 250 mg/kg body weight provided protection against the ulcerogenic effect of naprosyn under dissecting microscope. Under laboratory microscope, a significant increase in the mucosal thickness with the administration of paracetamol followed by naprosyn was observed, while the flattening of the surface epithelium with slight exfoliation may be attributed to relative increase of pepsin from the chief cell. The increased secretory activity of the mucous neck cells in animals treated with paracetamol followed by naprosyn may be due to the increased bio-synthesis of prostaglandin from these cells which might have produced protective influence against the damaging effect of naprosyn. PMID- 1861356 TI - Coronary thrombolysis--a Pakistani perspective. PMID- 1861355 TI - Non-Hodgkin's lymphoma of thyroid. PMID- 1861357 TI - A story of histopathological hunt. PMID- 1861358 TI - Lead--an essential trace element. PMID- 1861359 TI - Psychosocial aspects of dialysis and renal transplant. PMID- 1861360 TI - Psychosocial adjustment after renal transplantation. AB - Renal Transplantation is fairly new in our country and is expected to be the only satisfactory long-term treatment for patients with End Stage Renal Disease. Such treatment offers them a chance for near normal life. Seventeen patients who underwent kidney transplant during 1987-88 at the department of Nephrourology of J.P.M.C. Karachi, were reviewed. The result of ten patients who were assessed for their psychosocial adaptation is presented. PMID- 1861361 TI - Psychosocial aspects of dialysis and renal transplant. AB - Keeping in view our socio cultural millieu, the psychological aspects of twenty renal transplants recipients and equal number of patients on dialysis were studied. Socio psychiatric profile in the dialysis and transplanted patients revealed that the frequency of anxiety, depression and hypochondriasis was significantly less (P less than 0.01) in the transplanted group. On Bender Gestalt Scale the transplanted group achieved normal status in significantly higher (P less than 0.05) number compared to the dialysis patients. It was concluded that transplanted patients showed marked improvement in social functioning, psychological symptoms and enduring personality traits compared to patients on maintenance dialysis. PMID- 1861363 TI - [Drug therapy]. PMID- 1861362 TI - [Basic theory of drug administration--pharmacokinetics and pharmacodynamics]. PMID- 1861365 TI - [Diagnosis and treatment of subdiaphragmatic abscess]. AB - The author analyses the results of examination and operative treatment of 38 patients with subdiaphragmatic abscesses. Their ages ranged from 21 to 65 years. There were 29 males and 9 females. It was established that the diagnosis of subdiaphragmatic abscesses should be based on clinical, laboratory, radiological, and ultrasonic data. The results of treatment of these patients are determined by timely recognition of this complication and the terms of the surgical intervention. PMID- 1861364 TI - [Therapeutic agents]. PMID- 1861366 TI - [Endoscopic glue infiltration and diathermocoagulation in the complex treatment of patients with acute gastroduodenal hemorrhages]. AB - A special medicinal glue MIK-T capable of infiltrating biological tissue by means of an endoscopic needle was developed. The authors suggest a method for glue endoscopic infiltration of the source of gastroduodenal bleeding for its arrest and prevention of a recurrence. Experimental study was undertaken to study the efficacy of glue endoscopic infiltration, determine the terms of glue resolution, and reveal the morphological changes in the zone of glue injection. The method of glue endoscopic infiltration was employed in complex treatment of 109 patients with acute gastroduodenal bleeding. The results provide evidence of the high efficacy of the method and its advantages over diathermocoagulation in arresting and preventing recurrences of acute gastroduodenal bleeding. PMID- 1861367 TI - [A clamp for suturing of duodenal stump]. AB - An original clamp was used in suturing a duodenal stump after gastric resection in 77 patients. The complex relief of the blades of the clamp holds the duodenum reliably during application of the sutures and ensures their air-tightness. The trauma inflicted to the duodenum in this case is minimal. During resection of the stomach in 37 patients the author used the clamp in closure of the lesser curvature. Incompetence of the duodenal stump was not encountered. PMID- 1861369 TI - [Hemorrhage from the gallbladder artery into the abdominal cavity]. PMID- 1861368 TI - [Colectomy with resection of the rectal mucosa and formation of the ileo-rectal anastomosis as an alternative of permanent ileostomy]. AB - A new method for surgical management of patients with diffuse polyposis of the large intestine is described. It was applied in 22 patients with total involvement of all parts of the large intestine in polyps. The essence of the suggested operation consists in preservation of the rectum after its demucosation and the formation of a cecal++-ileorectal anastomosis at the level of the pelvic peritoneum. The operative techniques are described. Experience in various types of intestinal anastomoses with a demucosated rectum as well as the techniques of the most optimal anastomosis are analysed. Retrospective analysis of the results of treatment allowed the authors to conclude that in inclusion of demucosated rectum into the intestinal passage its reservoir and accumulative function is maintained. Follow-up of the patients showed that small intestinal type mucosa regenerates in the rectum after mucosectomy in one third of patients and colonic type mucosa in the remaining patients. It is pointed out that recurrent growth of polyps in the rectum after adequate demucosation was not encountered. PMID- 1861370 TI - [Perforation of the transverse colon after electrocoagulation]. PMID- 1861372 TI - [Xanthogranuloma of the mesentery of the transverse colon]. PMID- 1861371 TI - [Simultaneous surgical treatment of giant ventral hernia and large stomach ulcer]. PMID- 1861373 TI - [Multiple perforations of the small intestine in cholelithiasis- induced intestinal obstruction]. PMID- 1861374 TI - [Combined complications of stomach ulcer]. PMID- 1861375 TI - [Perforation of the small intestine by a foreign body in incarcerated hernia of the spigelian line]. PMID- 1861376 TI - [Endoscopic papillotomy]. PMID- 1861377 TI - [Use of laser welded suture on the blood vessels and in surgery of the gastrointestinal tract]. PMID- 1861378 TI - [Is selective proximal vagotomy expedient in the treatment of bleeding duodenal ulcers?]. AB - The article analyses the results of truncal and selective proximal vagotomy with gastric draining operations in 101 patients with bleeding duodenal ulcer. The patients' condition, the results of special methods of examination, and the morphological changes in the gastric mucosa were studied. It was found that selective proximal vagotomy with drainage of the stomach had no advantages over truncal vagotomy. Besides, being a technically more difficult operation than truncal vagotomy, it fails to meet the requirements of emergency surgery and its application in patients with a bleeding duodenal ulcer isnot expedient. PMID- 1861379 TI - [Predicting the risk of recurrence of duodenal ulcer after vagotomy]. AB - The author suggests a multifactor program for decoding the variant of the course of the postoperative period in patients with duodenal ulcer. It was tested in 199 patients. Three groups of patients with a favourable prognosis, an uncertain prognosis, and with a high risk of recurrent ulcer were distinguished. An individual therapeutic program with consideration for the risk group allows the incidence of postoperative recurrence of ulcer to be reduced by more than three times. PMID- 1861380 TI - [Extended selective proximal vagotomy in the treatment of duodenal ulcer complicated by hemorrhage and perforation]. AB - The article analyses surgical treatment of 280 patients, aged from 19 to 20 years, with duodenal ulcer complicated by hemorrhage (36.1%) and perforation (63.9%). Closure of the perforating ulcer with sutures was performed in 15%, resection of the stomach in 12.8%, truncal vagotomy in 7.5%, and expanded selective proximal vagotomy in 64.7% of patients. Comparative analysis of the immediate and late-term results of closure of the perforating ulcer, resection of the stomach, and organ-preserving operations showed that expanded selective proximal vagotomy has unquestionable advantages over the other operations mentioned above. It is not marked by mortality and severe postoperative complications, it leads to stable suppression of acid production by the stomach, has a minimal effect on its motor-evacuation activity, shortens the time needed for healing of the ulcer by 16.3 +/- 1.7 days, and leads to rare (2.2%) recurrences of the disease. PMID- 1861381 TI - [Prevention of incompetence of esophageal sutures]. AB - Patients suffering from esophageal and gastric diseases were divided into 2 clinical groups: main (133) and control (115 patients) groups. In the main group particular attention was focussed on correct formation of the grafts, precision techniques of application of the sutures of the anastomosis, the use of laser, and adequate correction of the alimentary and immunological status. The incidence of incompetence of the esophageal anastomoses reduced from 12.2 to 0.8%. Fatal outcomes were not encountered in the main group, 9 patients died in the control group. PMID- 1861382 TI - [Post-vagotomy disorders in patients with duodenal ulcer in relation to the method of proximal gastric vagotomy]. AB - The article deals with the results of study of the effect of the degree of inhibited gastric acid-producing activity on the frequency of the development of postvagotomy disorders (PVD) in 158 patients with duodenal ulcer after treatment by various methods of proximal gastric vagotomy (PGV) and PGV with a stomach draining operation. The frequency and severity of PVD were found to correlate intimately with the degree of inhibition of the gastric acid-producing activity by the PGV and the character of the draining operation. PVD were more severe and encountered more frequently in patients in whom HCl secretion was inhibited by 80% and 100% as compared to the initial value, especially in patients who underwent a stomach-draining operation. Organic PVD (stenosis, an indolent or a recurrent ulcer adhesions) are mostly encountered in the late-term postoperative period. PMID- 1861383 TI - [Diagnostic value of cholinolytics in the surgical treatment of peptic ulcer]. AB - From study of the results of treatment of 157 patients with gastric and duodenal ulcer by an individual approach to the choice of the operative methods according to the results of prognostic tests, the authors revealed a high practical significance of using cholinolytics for diagnostic purposes. The choice of the method of surgical treatment with due regard for the prognostic evaluation of the effect of vagotomy on the gastric motor and acid-producing functions determined a 8.4% reduction of the frequency of postoperative motor-and emptying complications of gastric activity, and a 6.8% reduction of the incidence of recurrent ulcer. PMID- 1861384 TI - [Treatment of peptic ulcer hemorrhages]. AB - The article analyses experience in treatment of 297 patients with gastroduodenal bleeding of ulcerous etiology. Operative interventions after arrest of bleeding and the appropriate preoperative management produce better results (the mortality rate, 3.3%) than those of emergency operations (the mortality rate, 15.7%). It is therefore advisable to start treatment of patients with gastroduodenal bleeding by means of nonoperative measures which proved effective in 61.6% of cases. In doubtful reliability of hemostasis, patients with moderate and severe bleeding should be operated on in the immediate days after hospitalization without waiting for a possible recurrent bleeding. Gastric resection is the main type of operative intervention in bleeding from a gastric ulcer. In a bleeding duodenal ulcer both resection of the stomach and economical operations--vagotomy, excision or closure of the ulcer, pyloroplasty--are equally competent. PMID- 1861385 TI - [Vascular structure and the microcirculatory bed of the stomach after selective proximal vagotomy]. AB - The authors conducted experiments on 30 dogs for periods of 1-7 days to 12 months and established that a sharp disorder of microcirculation occurs in the postoperative period, particularly in the cardia and fundus of the stomach, due to denervation and devascularization which lead to stasis in the venous system, hypoxia, and ischemia. The microcirculatory disorders are restored in 6 to 12 months. The study showed that the use of selective proximal vagotomy in true gastric ulcers is not expedient. PMID- 1861386 TI - [Tubular gastrectomy with selective vagotomy in the treatment of peptic ulcer]. AB - The authors generalize the material on the surgical treatment of 151 patients who were operated on for complicated gastroduodenal ulcers by means of an improved method of tubular resection of the stomach with selective vagotomy, subtotal excision of the lesser curvature, and the formation of a ++post-colonic rectangular gastroenteroanastomosis on a short loop with oblique division of the jejunum. The late-term results were studied in follow-up periods of up to 4 years in 110 patients (72.8%) and appraised according to Visik's scale. The results were excellent in 78 (70.9%), good in 25 (22.7%), satisfactory in 6 (5.5%) patients, and poor (recurrence of the disease) in one (0.94) patient. PMID- 1861387 TI - [Functional state of the stomach after vagotomy and the correction of various post-vagotomy complications]. AB - The author studied the secretory and motor-emptying function and the endoscopic picture of the stomach after various types of vagotomy conducted for peptic ulcer in 84 patients. The effect of the motor-evacuative function on the secretion values is shown. It is pointed out that secretion must be studied after restoration of adequate motor-emptying function, which is normalized 3-6 months after the operation. The endoscopic picture of the stomach depends on the type of the auxiliary operation on the stomach and the lapse of time after the operation, and the existence of reflux. The author suggests a differentiated complex of rehabilitation therapy including endogenous intracavitary pneumomassage of the stomach, its percutaneous electrostimulation, and the intake of mildly mineralized water; early application of these measures raises the efficacy of the surgical treatment. PMID- 1861388 TI - [Use of a single-row suture in surgery of the gastrointestinal tract]. AB - The authors show the results of experimental and clinical study of a single-row Pirogov-Mateshuk serous-muscular-subserous suture with the knots inside the lumen. It was demonstrated in experiments on 191 dogs that regeneration in the zone of anastomoses formed by a single-row suture is more perfect and occurs earlier than with the application of a double-row suture. Among 2,623 anastomoses formed on the esophagus, stomach, small intestine, colon, and rectum by means of a single-row suture, 1.5% were incompetent. The authors consider the single-row Pirogov-Mateshuk suture to be the method of choice. PMID- 1861389 TI - [Bilateral exclusion of the duodenum in reconstructive surgery of the stomach]. AB - The article analyses the results of modified gastric resection after Roux with bilateral exclusion of the duodenum in 13 patients with disease of an operated stomach. The operations were performed for peptic ulcer of the gastroenteroanastomosis in 5 patients, for biliary reflux gastritis in 3, and for reflux gastritis and coexistent Stages II-III dumping syndrome in 5 patients. The outcomes of treatment were studied in follow-up periods of up to 3 years. The results were good in 10 patients, satisfactory in 2, and poor in 1 patient. Recurrent peptic ulcers were not encountered. The clinical picture of biliary reflux gastritis was completely relieved in all of the 8 patients. The dumping syndrome phenomena were arrested in 2 patients and relieved significantly in another 2. PMID- 1861390 TI - [Enteral correction in gastroduodenal hemorrhage of peptic ulcer etiology]. AB - Among 115 patients with gastroduodenal hemorrhage 60 received nonoperative treatment, 30 of them underwent enteral correction with a monomer electrolyte solution. Emergency operation was carried out on 55 patients, 35 of them were subjected to enteral correction in the postoperative period. Enteral administration of the monomer electrolyte solution in the early posthemorrhagic and postoperative periods promoted filling up of the blood circulation volume and its components and stabilization of the values of central hemodynamics. It was established on grounds of the clinical data, studies of the volemic indices and central hemodynamics that enteral correction does not yield to the traditional intravenous infusion-transfusion therapy in efficacy. PMID- 1861391 TI - [Gastrointestinal hemorrhage after operations for perforated gastroduodenal ulcers]. AB - On the basis of clinical observation over 521 patients who underwent operations in the clinic for perforating gastric and duodenal ulcer, the authors determined the frequency of massive gastrointestinal hemorrhage (3.2%) in the early postoperative period and the mortality rate in this complication. It is shown that the performance of radical surgical interventions instead of simple closure of the perforating ulcer with sutures, in the absence of life-threatening concomitant diseases and the terminal phase of peritonitis, may improve the results of operative management of this disease. PMID- 1861392 TI - [Techniques of anastomoses in the gastrointestinal tract]. AB - The authors analysed 718 operative interventions in which gastrointestinal anastomoses were formed at various levels of the gastrointestinal tract. It was established that the more distal the anastomosis is, the greater the risk of its incompetence and a fatal outcome due to it are. The advantages of the "closed" method for forming the anastomosis in operations on the ileum and colon were revealed. A method for creating anastomoses by the closed technique with a single row suture is suggested. PMID- 1861393 TI - [Modification of gastrectomy by the Roux and Ridiger methods]. AB - The author recommends a more effective operative method after Roux-Ridiger with an invagination intestinal anastomosis in the management of severe complications of gastric and duodenal ulcer, particularly in duodenostasis and reconstructive operations for a disease of an operated stomach, and in the postvagotomy syndrome. He carried out 340 economical resections of the stomach after Roux Ridiger with an invagination intestinal anastomosis in various complications of gastric and duodenal ulcer and the post-gastrectomy and postvagotomy syndromes. The immediate and late-term results of the operation were good. Modified gastric resection after Roux and Ridiger with invagination techniques was performed in 26 experimental dose to study the secretory and motor-emptying function of the gastric stump in the immediate and late-term periods after the operation; the results were good. PMID- 1861394 TI - [Status of protective properties of the gastroduodenal mucosa after surgical treatment of duodenal ulcer]. AB - The defense properties of the gastroduodenal mucosa (lymphoid system cells secreting immunoglobulins A, M, and G, as well as the secretory component IgA) were studied in 85 patients with duodenal ulcer. The acid-producing function of the stomach was tested at the same time according to the pH value and the basal and maximal acid production. Various types of vagotomy were conducted in 52 patients and resection of the stomach in the remaining patients. The results were followed-up before and after the operation. Peptic ulcer was characterized by secondary immunodeficiency. Selective proximal vagotomy restored the tissue immune defense of the mucosa, gastric resection preserved and even increased immunodeficiency. PMID- 1861395 TI - [Morpho-functional characteristics of invagination esophago-enteric and esophago gastric anastomoses]. AB - The morphological and functional features of invagination ++esophago-enteric and esophagogastric anastomoses were studied in 234 of 266 patients who underwent gastrectomy or proximal resection of the stomach for cancer in 1972-1989. Two valuable stable properties were found to be characteristic in normally functioning invagination anastomosis: reliable anti-reflux properties and evacuation in portions. They are ensured by the obturating apparatus of the anastomosis, which consists of a valve and a muscular sphincter. No functional disorders on the part of the anastomosis were encountered in all periods after the operation in 174 (74.4%) patients. Complications developed in 60 (25.6%) patients (acute anastomositis, spasm of the anastomosis, reflux esophagitis, cicatricial stricture, and the dumping syndrome); they were attended by disorders of the function of the anastomosis due to temporary or constant disorders of the function of the obturating apparatus. PMID- 1861397 TI - [Hyperbaric oxygenation in the treatment of bleeding gastroduodenal ulcers]. AB - It is shown on the basis of analysis of the results of treatment of 179 patients that the use of hyperbaric oxygenation in the complex surgical management of ulcerative gastroduodenal bleeding reduced the number of postoperative complications by a factor of 3.3 and led to a decrease of mortality from 20 to 1%. The authors confirm the expedience of including hyperbaric oxygenation in the complex of therapeutic measures in patients with bleeding ulcers under conditions of accomplished hemostasis by conservative or surgical methods in one of three suggested variants: in preparation of the patients for operation in the postponed period; after operative interventions carried out at the peak of bleeding; before and after operations on patients with moderate and severe blood loss and concomitant diseases. The sessions should be conducted under pressure of 2 atm for 60 minutes. PMID- 1861398 TI - [Immunological aspects of restorative processes during rehabilitation of patients with peptic ulcer after surgical interventions]. AB - The authors studied the immunological and endocrine status of 296 patients in the early periods, in 2-3 weeks, after resection of the stomach or selective proximal vagotomy for complicated peptic ulcer or inefficacy of nonoperative treatment. Imbalance in the cellular and humoral links of immunity was revealed, which was characterized by the presence of the autoimmune component, depression of the T lymphocyte system and changes of its functional activity, unbalanced regulatory processes of immunocompetent cells, increase of the humoral link of immunity, diminished biological resistance of the organism, which were manifested to an equal degree in patients who underwent various types of operations. A close correlation of immune and endocrine disorders was revealed. Under the effect of rehabilitation measures positive shifts occurred in the disturbed indices of the immune and endocrine systems, which suggests that the application of physical factors promotes processes of natural immunity and the course of restorative and regenerative processes in rehabilitation of patients who underwent an operation. PMID- 1861396 TI - [Endoscopic evaluation of various methods of anastomosis after gastrectomy]. AB - Resection of the stomach is still the principal method for surgical management of gastric and duodenal ulcer. The functional condition of the anastomosis depends on the method used. The authors conducted comparative endoscopic evaluation of anastomoses formed after Hofmeister-Finsterer, Billroth I, Andreo and Vitebsky according to the following criteria: shape and diameter; contractile and obturator function; gastrointestinal reflux; morphological changes in the zone of the anastomosis and the gastric stump. The authors analyse their own material concerning fibrogastroscopy in 168 patients after gastric resection, the anastomosis was established after Hofmeister-Finsterer in 93 of them after Vitebsky in 46, after Billroth I in 21, and after Andreo in 8. Vitebsky's modification of Billroth II anastomosis and Andreo's modification of Billroth I anastomosis possess the best functional capacities. Billroth I and Billroth II gastroenterostomy in Hofmeister-Finsterer's modification do not possess contractile and obturator property, which promotes reflux of bile into the gastric stump and the development of reflux gastritis and other complicating factors. PMID- 1861399 TI - [Preparation of patients with double-channel and marginal colostomies for restorative treatment]. AB - The data on restorative treatment of 215 patients with double-channel and terminal colostomy are analysed to determine the efficacy of total lavage of the gastrointestinal tract in preparation of patients for operation. Postoperative complications occurred in 52.4 +/- 3.8% of patients prepared by a diet, purgatives, and enemas and in 34 +/- 6.9% in those prepared by the method of total lavage of the gastrointestinal tract (p = 0.021). Neither suppuration of wounds nor incompetence of the restorative anastomosis occurred after lavage. PMID- 1861400 TI - [Immunologic status and its correction in amebic liver abscess]. AB - The author analyses the results of study of the immune status in 100 patients with amebic abscess of the liver, who were divided into 2 groups. In an uncomplicated course of the disease (50 patients, Group 1) there were no essential shifts in the immune status in the preoperative period. In the postoperative period (1st-3rd day), however, the percentage and absolute number of T- and B-lymphocytes reduced. Due to this, immunostimulation therapy (decaris, gamma-globulin, hyperimmune antistaphylococcal plasma, activin) had to be applied. In a complicated course of amebic abscess of the liver (50 patients, group 2) the water-electrolyte metabolism was disturbed and the blood erythrocyte globular volume was reduced and the cellular and humoral links of immunity were markedly depressed in the preoperative period. Intensive transfusion-infusion therapy had to be conducted along with immunostimulation treatment (decaris, T activin, gamma-globulin, hyperimmune antistaphylococcal plasma, direct transfusion of blood) and prescription of anabolic hormones (pentoxyl, retabolil). PMID- 1861401 TI - [Visual results of extracapsular cataract surgery with posterior chamber lenses]. AB - In a total of 1663 consecutive patients best corrected visual acuity after extracapsular cataract extraction with implantation of a posterior chamber lens was determined. Average follow-up time was 21 months. Visual acuity improved from an average of 0.15 preoperatively to 0.6 postoperatively. In the absence of other ocular disorders postoperative vision averaged 0.7. The visual outcome was clearly related to the age of the patients and showed a continuous decline for operations performed after the age of 69 years. PMID- 1861402 TI - [Clinical studies of eye involvement in porphyria cutanea tarda]. AB - In 1980 we started a long-term study at our department examining 54 Patients with p.c.t. (42 male, 12 female). Out of these patients, 32 were re-examined (23 male, 9 female) in 1986. No ocular lesions were found that might be attributable to the underlying disease. Possible symptoms of p.c.t. are an increased filling of the conjunctival vessels, a decreased tear's formation, as well as brownish pigmentations in conjunctiva, in the lid margin. These changes occur in the anterior eye segment. At the fundus, a dry, in part side-different macular destruction and uncharacteristic peripheral retinal degeneration were found. The most prominent functional disorders are the acquired colour vision deficiency Verriest Type III and FSM Type I, respectively. It is based upon the small decrease of the visual acuity (relative central scotoma), the decline in immediate adaption and the macular destruction. Possible etiopathogenetical links between the underlying disease and the tapetoretinal degeneration are discussed. The morphological and functional eye lesions are limited and show hardly any progression. PMID- 1861403 TI - [Use of liquid perfluorocarbon in giant tears. Initial results]. AB - Ten consecutive cases of giant tears with retinal inversion were easily and successfully treated using vitrectomy and silicone oil injection after repositioning the retina with liquid perfluorocarbon. The good initial results show the interest of this technique compared with earlier manipulations of the retina. PMID- 1861404 TI - [Involuntary lid closure caused by defective healing of facial paralysis and its treatment with botulinum toxin]. AB - Unvoluntary lidclosure with movement of the mouth is not so rare in aberrant regeneration of nerve fibers after Bell's palsy. There was no therapy until now. 10 patients with this disease were treated with botulinum-toxin injections into the orbicularis muscle. For an average time of 11 weeks after injection there was a complete absence of synkinesis, followed by a time of 9 weeks of less complaints. Thus 2-3 injections might be sufficient treatment within a year. Complications worth mentioning, especially due to the reduced force of lidclosure, were not observed. PMID- 1861405 TI - [Detection of progressive glaucomatous papilla changes before onset of visual field defects]. AB - Computerized disc analysis was used for the longitudinal monitoring of patients with moderate intraocular pressure elevation. 44 patients (80 eyes) were monitored for at least 18 months; 25 patients (47 eyes) were monitored for at least 12 months; 15 patients (25 eyes) were monitored for at least 18 months. On average, one computerized disc analysis was performed every 4 months. Eight eyes showed a progressive decrease in their neuroretinal rim area. Seven of them were monitored for more than 18 months, one was monitored for 15 months. In all cases, the progressive decrease in neuroretinal rim area was significant, p less than or equal to .1. It is non-physiological and has to be interpreted as a serious sign of ongoing glaucoma damage. In addition, it obviously precedes the onset of visual field defects. Seven out of 8 eyes with progressive decrease in their neuroretinal rim area have normal visual fields up to now. In one case a progressive decrease in neuroretinal rim area was found at first and small visual field defects developed subsequently. PMID- 1861406 TI - [Glaucoma screening--justified or not justified?]. AB - In explaining the damages of primary open-angle glaucoma, the elevated eye pressure was assumed to be the central causative factor. But epidemiological research found high proportions of the following clinical entities: only elevated pressure without further damages (called ocular hypertension), and only glaucomatous damages without high pressure (called normal- or low-pressure glaucoma). These facts made the pressure-theory doubtful, and therefore it had to be modified. Some authors, though, doubt the general validity of the pressure theory, and postulate other models for the etiology of glaucomatous damages. According to current knowledge, for the diagnosis and screening of primary open angle glaucoma, emphasis should be put rather on the visual fields and the appearance of the optic disc, while pressure measurements supply further clues. PMID- 1861407 TI - [A new photographic method for measuring squint angles in infants and small children]. AB - A new photographic method for measuring squint angles in children and infants is presented. A photographic picture is taken from the subject, using a camera with the three flashes bulle. One flashbulle is placed vertically over the lens, two other flashbulles are placed symmetrically in an angle of 10 degrees beside the middle flash. Six reflections can be seen on the photographic picture in each pupil. (1. and 4. Purkinje Sanson Images of each light source.) The horizontal distance of two reflections is determined by the distance of the flashguns. If the reflection lines in both eyes are symmetrical, there is no squint. If there is a shift, it can be measured on the slide and by using a simple formula the squint angle can be calculated. The accuracy of the method is between 2 and 3 degrees. PMID- 1861408 TI - [Acanthamoeba keratitis in hard contact lens wearers. Case report and review of the literature of 108 cases]. AB - We report on a 49 year old woman with Acanthamoeba keratitis. She was wearing hard contact lenses and had a history of a minor trauma when removing her lens after a visit of a hot tub. She had the typical corneal ring infiltrate and complained about severe pain. The medical treatment was uneffective. Because of progressive deterioration penetrating keratoplasty was necessary. After a rekeratoplasty because of a recurrent infection on the transplant the patient has done well now for 3 years. The diagnosis was made on histological grounds. We report on 108 patients of the literature: 8 (7%) patients were wearing hard contact lenses; 19 (17%) remembered a trauma; 4 (3.7%) had visited a hot tub; 61 (56%) needed penetrating keratoplasty, 11 (10%) rekeratoplasty; 5 (4.6%) eyes were enucleated; in 21 (19%) patients the diagnosis was made on histological grounds. PMID- 1861410 TI - [History of the Berlin Ophthalmology Society]. AB - To mark the congress of the Berlin Ophthalmological Society in December 1989, the authors review the development of ophthalmology in Berlin and in particular the history of this ophthalmological society. The review was prompted by the political changes which began in October 1989, enabling ophthalmologists from the eastern part of the city to attend the congress in West Berlin for the first time in 28 years. PMID- 1861409 TI - [A new permanent magnet for removal of intra-ocular ferromagnetic foreign bodies]. AB - The permanent-magnet (Sm-Co-Magnet) is described with a length of 35 mm and a diameter of 18 gauge. This magnet enables a controlled atraumatic removal of small or even larger intraocular ferromagnetic foreign bodies. PMID- 1861411 TI - [Development of the new district federations of the German Nursing Association]. PMID- 1861412 TI - [Occupation-political consequences of health-oriented nursing]. PMID- 1861413 TI - [The training situation in the Berlin nursing schools]. PMID- 1861414 TI - [Work satisfaction of nurses in night shift. Report by the project group "The last hours of night in the hospital from the night nurse's viewpoint"]. PMID- 1861415 TI - [Settlement agreements with private duty nurses]. PMID- 1861416 TI - [Namaste, namaste sister! or: showers only when the sun shines! Impressions and experiences during voluntary work in a nursing home in Katmandu, Nepal]. PMID- 1861417 TI - [Working relations between nurses and physicians in Great Britain: frequently disturbed]. PMID- 1861418 TI - [Foundations of occupational law (III). Who is the employee?]. PMID- 1861419 TI - [Guide to cultural evaluation. Discovering other philosophies of life]. PMID- 1861420 TI - [Ethics and transplantations in Switzerland. Towards better understanding]. PMID- 1861421 TI - [Nursing care and the "mother hen" syndrome]. PMID- 1861422 TI - [Study of breast feeding and fertility in Bolivia. A holistic approach to the family]. PMID- 1861423 TI - [Exhibition in Berne. Great disease outbreaks--great cures]. PMID- 1861424 TI - [Residences of practical nursing for teachers. Clarifying the purpose]. PMID- 1861425 TI - [Rediscovery of a natural remedy: honey on the wound]. PMID- 1861426 TI - [From individual nursing to running a team--results of a supervision. Efficiency through reorganization]. PMID- 1861428 TI - [Academic continuing education in nursing--what for?--report from a meeting. University studies for nurses!]. PMID- 1861427 TI - [Job hunting: what are the possibilities?]. PMID- 1861429 TI - [Mentors--they advance us and charge us]. PMID- 1861430 TI - [Intuition: "Practiced recognition of patterns"]. PMID- 1861431 TI - [Reflections on the symposion on the 26 and 27 April of this year at the congress center in Lugano: Organ transplantation: honors and conflicts]. PMID- 1861432 TI - [Working with those looking for asylum]. PMID- 1861433 TI - [Headaches--mostly a disease of women. Headaches interfere considerably with work efficiency]. PMID- 1861434 TI - [The Swiss Nursing Federation is reorganizing its forces]. PMID- 1861435 TI - [Introduction into the world of a psychiatry department. Letter to a beginner in psychiatry or: the hospital belongs to the nurses]. PMID- 1861436 TI - [To unite in order to be heard more clearly]. PMID- 1861437 TI - [Home care. The role of natural liability]. PMID- 1861438 TI - [Nursing an Alzheimer patient]. PMID- 1861439 TI - [Job hunting using newspaper advertisements]. PMID- 1861440 TI - [Shortage of personnel--a push for change]. PMID- 1861441 TI - [Immunotherapy with interleukin 2]. PMID- 1861443 TI - [Decubitus ulcer--a nursing problem?]. PMID- 1861442 TI - [What are the tasks of the nursing personnel after kidney transplantation?]. PMID- 1861444 TI - [Decubitus ulcer: effective treatment is possible]. PMID- 1861445 TI - [Skin care as a precondition for the prevention of decubitus ulcers]. PMID- 1861446 TI - [Urine drainage in transurethral interventions--experiences with a complete-set for suprapubic drainage]. PMID- 1861447 TI - [Conservative therapy in hyperactive detrusor muscle in women and special aspects in children]. PMID- 1861448 TI - [Electrostimulation as an aid in fecal incontinence]. PMID- 1861449 TI - Ornithine transcarbamylase deficiency: findings and treatment in a symptomatic female heterozygote. PMID- 1861450 TI - Chronic coagulopathy in a patient with argininosuccinase deficiency. PMID- 1861451 TI - Acute neonatal isovaleric acidaemia presented without acidosis or ketonuria. PMID- 1861452 TI - A false hyperglycinaemia. PMID- 1861453 TI - Methylmalonic aciduria presenting in an adult. PMID- 1861454 TI - Galactose increase in an infant whose mother is heterozygous for peripheral uridine diphosphate galactose-4-epimerase deficiency. PMID- 1861455 TI - Complementation studies in human and caprine beta-mannosidosis. AB - Cell fusions were performed to investigate the possible involvement of different gene mutations in five patients with isolated beta-mannosidosis and a patient with a combined deficiency of beta-mannosidase and heparin sulphate sulphamidase. In none of the combinations of cell lines was beta-mannosidase activity restored in the fused cell culture. Similarly, no complementation of sulphamidase activity was observed after fusion of cells with the combined deficiency and cells with isolated sulphamidase deficiency (mucopolysaccharidosis type IIIA). The absence of complementation suggests that the combined deficiency is not caused by a defect in one common factor affecting the two enzymes: The results rather indicate a rare coincidence of two independent mutations which are allelic with the mutation in the respective conditions with isolated enzyme deficiencies. PMID- 1861456 TI - beta-mannosidase deficiency in a female infant with epileptic encephalopathy. AB - We report a female infant with an isolated deficiency of beta-mannosidase activity. At nine months of age dysmorphism was absent except for brachecephaly. There was moderate developmental delay and a startle response to sound. At 12 months there was a sudden onset of tonic-clonic seizures which were unresponsive to drug therapy, requiring paralysis and mechanical ventilation for control. The child died suddenly aged 15 months. beta-mannosidase activity was markedly reduced in white cells and cultured skin fibroblasts whilst other lysosomal enzymes were normal. The disaccharide ManGlcNAc was excreted in urine but urinary mucopolysaccharides were normal. PMID- 1861458 TI - Confocal scanning laser microscopy of mitochondria: a possible tool in the diagnosis of mitochondrial disorders. AB - This paper describes a non-invasive method for the study of mitochondrial morphology in cultured human skin fibroblasts by confocal scanning laser microscopy after staining the mitochondria with 2-[4-(dimethylaminostyryl]-1 methylpyridinium iodide. This method is applied to compare mitochondria in fibroblasts from healthy individuals and from patients with mitochondrial myopathy. In most cases there is a striking swelling of the patient's mitochondria and a loss of fine structure. The results with respect to the potential of this method as a diagnostic tool are discussed. PMID- 1861457 TI - Altered phosphorylation state of branched-chain 2-oxo acid dehydrogenase in a branched-chain acyltransferase deficient human fibroblast cell line. AB - The abundance and phosphorylation state of the polypeptide constituents of the human branched-chain 2-oxo acid dehydrogenase complex were examined in mitochondria from normal and maple syrup urine disease (MSUD) fibroblasts. In normal fibroblast mitochondria two forms of the E1 alpha subunit were observed: non-phosphorylated (E1 alpha) and phosphorylated (E1 alpha-P). About 40-50% of E1 alpha was present as E1 alpha-P. The ability to quantitate the two forms of E1 alpha permitted examination of the association between decreased capacity of oxidize branched-chain 2-oxo acids and the phosphorylation state of E1 alpha. Changes in phosphorylation state of E1 alpha were observed in MSUD fibroblasts as compared to control cells. Of particular interest was the absence of E1 alpha-P in an MSUD fibroblast line which lacked the dihydrolipoyl acyltransferase (E2) subunit of the dehydrogenase complex. In two MSUD cell lines deficient in E1 alpha, the abundance of E1 alpha-P appeared to be preferentially reduced. A fourth MSUD cell line contained normal quantities of E3, E2 and both forms of the E1 alpha polypeptide. Our results indicate that alterations in the abundance of dehydrogenase complex polypeptides in MSUD fibroblasts may influence the phosphorylation state of the E1 alpha polypeptide. They demonstrate the potential for examining simultaneously mutations which affect both the catalytic and regulatory components of the dehydrogenase complex. PMID- 1861459 TI - Successful treatment of dihydropteridine reductase deficiency, with an interesting effect of 5-hydroxytryptophan deficiency on sleep patterns. AB - We report a child in whom dihydropteridine reductase deficiency was diagnosed prenatally because of an affected sibling and who was treated from birth with apparent good response. This family has been reported before (Firgaira et al., 1980, 1981, 1983; Lipson et al., 1984; Cotton et al., 1986; Dahl et al., 1988). The parents are Lebanese Muslims who are first cousins, and their first and third children, both male, are well. The third child was diagnosed as normal in utero (Firgaira et al., 1983). The second child, the subject of an early report (Lipson et al., 1984), has dihydropteridine reductase deficiency. The dihydropteridine reductase is nonfunctional due to an amino acid insertion (Howells et al., 1990). PMID- 1861460 TI - Renal failure in adult patients with hereditary tyrosinaemia type I. AB - An adult patient with hereditary tyrosinaemia type I who developed renal failure is reported. She received a renal transplant at the age of 23 years. In childhood her kidney disease was dominated by multiple tubular defects with resulting hypophosphataemic rickets. Metabolic acidosis was the most prominent feature in the years preceding the transplantation. Her kidneys were contracted to 40 g. The major morphological finding was that of a tubulointerstitial nephropathy. Liver biopsies taken at the ages of 5.5 and 23 years showed cirrhotic changes. Crystalloid inclusions in the liver mitochondriae were a prominent finding on electron microscopy. Fumarylacetoacetase was deficient in liver, kidneys, fibroblasts and lymphocytes. The typical biochemical parameters of tyrosinaemia, succinylacetone, p-hydroxyphenyllactate, p-hydroxyphenylpyruvate and serum tyrosine were only slightly elevated. A brief history of a second adult tyrosinaemia patient with decreasing renal function is also given. PMID- 1861461 TI - Urinary excretion of 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate and tiglylglycine after isoleucine loading in the diagnosis of 2-methylacetoacetyl CoA thiolase deficiency. AB - The concentrations of 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate and tiglylglycine were determined by gas chromatography-mass spectrometry in urine collected before and for 8 h after loading with 100 mg of isoleucine per kg of body weight. The sum of 2-methylacetoacetate and 2-butanone, a decarboxylation product, was determined as the 2-butanone dinitrophenylhydrazone derivative. Substantial increases in each compound were encountered in a patient with a documented defect of 2-methylacetoacetyl-CoA thiolase. Increased quantities of 2 methyl-3-hydroxybutyrate and tiglylglycine were also found in four children with clinical symptoms similar to those associated with 2-methylacetoacetyl-CoA thiolase deficiency but in whom the activity of the enzyme was found to be normal. The concentration of 2-methylacetoacetate plus 2-butanone in the urine increased after an isoleucine load only in the patient with 2-methylacetoacetyl CoA thiolase deficiency. PMID- 1861462 TI - Neonatal cardiomyopathy and lactic acidosis responsive to thiamine. AB - A congestive cardiomyopathy was diagnosed in a girl at the age of 4 weeks. In the weeks following she developed general muscle hypotonia and plasma lactate increased to 8.5 mmol/L. Biochemical investigations of a muscle biopsy at the age of 3 months showed a deficiency in the oxidation of all substrates tested: pyruvate plus malate, 2-ketoglutarate and palmitate plus malate. After freezing and thawing of the homogenate and the addition of essential cofactors, the oxidation of the ketoacids normalized. The oxidation defect in the untreated homogenate can be explained by a deficiency in one of the cofactors (such as thiamine pyrophosphate, NAD+ or CoASH), or by a defect in the oxidative phosphorylation. Treatment with thiamine and carnitine resulted in a decrease in blood lactate to normal levels and a dramatic clinical improvement. Suspension of thiamine caused deterioration of her clinical condition and lactic acidaemia. The thiamine therapy was then continued. The girl is now 6 years old and in perfect health. PMID- 1861463 TI - Hyperglycaemia associated with lactic acidaemia in a renal allograft recipient with type I glycogen storage disease. AB - Renal disease is a frequent and serious complication of type I glycogen storage disease. A type I glycogen storage disease patient with focal segmental glomerulosclerosis and progressive renal insufficiency underwent a renal allograft transplantation. Despite the same cornstarch therapy, the post transplantation course was complicated by worsening of the metabolic control manifested by exacerbated lactic acidaemia and hyperlipidaemia. This lactic acidaemia was remarkable for its association with hyperglycaemia. Hyperglycaemia accompanied by lactic acidaemia is strikingly unusual in type I glycogen storage disease, since this is a disease characterized by hypoglycaemia and an inverse relationship between blood glucose concentration and lactate levels. Both fasting insulin and C-peptide levels in the patient were greater than similar age-matched type I glycogen storage disease controls, indicating hyperinsulinaemia. The most likely mechanism responsible for the combined hyperglycaemia and lactic acidaemia was insulin resistance due to glucocorticoid treatment, instituted for immunosuppression. The hyperglycaemia associated with the lactic acidaemia was transient and resolved with steroid tapering. The exacerbated hyperlipidaemia, however, persisted after renal transplantation. Type I glycogen storage disease patients may be prone to glucocorticoid-induced insulin resistance, since the cellular metabolism in these patients may already be compromised with ineffective insulin action and/or reduced insulin output. PMID- 1861464 TI - The epidemiology of organ transplantation in South Carolina. PMID- 1861465 TI - Obtaining consent for organ donation: the role of the healthcare profession. PMID- 1861466 TI - Medical aspects of transplantation. PMID- 1861467 TI - Transplantation of gametes and embryos: an outgrowth of assisted reproductive technologies. PMID- 1861468 TI - Ethical considerations and controversies in transplantation. PMID- 1861469 TI - Third party payment and the cost of transplantation. PMID- 1861471 TI - Transplantation in South Carolina. PMID- 1861470 TI - Psychological and psychiatric aspects of organ and tissue transplantation. PMID- 1861472 TI - The history of transplantation. PMID- 1861473 TI - Evaluation of the endurance performance of marathon runners and theoretical analysis of test results. PMID- 1861474 TI - Effects of types and intensities of background music on treadmill endurance. AB - The effects of different types of music on heart rate (HR), rating of perceived exertion (RPE), and time to exhaustion during treadmill work were determined on 24 volunteer college students (Ss). The Ss participated in three randomly assigned multistaged treadmill walk/run to exhaustion while wearing a head-set. The three treatments were: loud, fast, exciting, popular music (Type A); soft, slow, easy-listening, popular music (Type B); and no music (control). HR was recorded at 0:30 of each minute until voluntary exhaustion. RPE was obtained after the test for five different points during the test. Differences (p less than 0.10) among experimental treatments were determined by a one-way ANOVA and Newman-Keuls. HR was lower with Type B music in minutes one and six. The peak HR and the HR in the minute preceding max were higher with Type B music. Time to exhaustion was longer during the Type B music treatment than during the control treatment. RPE was lower for Type B music than control during moderate work. This study provided some support for the hypothesis that soft, slow music reduces physiological and psychological arousal during submaximal exercise and increases endurance performance. PMID- 1861475 TI - A correlation between muscular strength and hydroxyproline concentration in human patellar tendon. AB - The connective tissue of the knee is frequently injured by athletes, especially those involved in contact sports. It would be important in the prevention of injury as well as the strategy of physical fitness training to know whether the connective tissue is modified in response to athletic stress or training. The potential modification investigated was variability in the concentration of hydroxyproline, a post-translationally modified imino acid found principally in collagen protein. A correlation was sought between this variability and the leg strength parameters torque (expressed as ft-lbs), torque/body weight and work (expressed as ft-lbs). In a preliminary study of five subjects, no correlation was found between hydroxyproline concentration of the patellar tendon and any of the leg strength parameters. These results suggest that this modification of the collagen in connective tissue does not occur in response to athletic stress or training, but rather, for the small number of subjects investigated, appeared to be relatively constant across a range of leg strengths. PMID- 1861476 TI - Are high-performance young women athletes doomed to become low-performance old wives? A reconsideration of the increased risk of osteoporosis in amenorrheic women. AB - Osteoporosis and athletic amenorrhea are now well-established findings in top level women athletes. Specifically trabecular bone appears to be affected. Since these two phenomena seem to occur simultaneously, questions have been raised as to the underlying mechanisms and whether physical exercise, which had been proven to exert a positive beneficial effect under normal conditions, should be held responsible. Although hypo-estrogenic status, body composition, and nutritional deficiency have been offered as possible explanations, none of these can be solely regarded as completely satisfactory. As for athletic amenorrhea itself, low estrogens are probably secondary to other phenomena and may only be related indirectly to osteoporosis. Whether they interfere with nutritional uptake is obscure. Possibly, endogenous opioid peptides are involved as an unnegligible mediator. As an important practical consequence it should be pointed out that osteoporosis in women athletes will be only detected incidentally; a fact which could obstruct timely intervention, though whether therapy is necessary remains open to discussion. The discovery that amenorrheic athletes subject to more severe training have a higher bone density than less engaged amenorrheic colleagues, can only be in favor of physical exercise, even under these conditions. PMID- 1861477 TI - Telethermography and Raynaud's phenomenon. AB - A Raynaud's Phenomenon reported by a young female athlete in concomitance with a traumatic injury occurred during her gymnastic performance is described. Discussion is carried out taking into account the recent acquisitions about the pathophysiology of this syndrome. PMID- 1861478 TI - Death due to fulminant toxic-shock syndrome: differential diagnosis of a multilayered clinical picture. AB - Reported is the case study of a 27-year-old top-performance sportswoman who died of a fulminant illness with multiple organ failure. Long-term polypragmatic therapy and pharmacotherapy as well as acute analgesic and non-steroid antirheumatic treatment due to lumbago led to the diagnosis of a "complex toxic allergic process". Numerous pathologic-anatomical findings, including the absence of septic spleen reaction and the demonstration of hyperacute polyradiculitis, supported this diagnosis. The present article discusses the possible differential diagnoses of the illness with the conclusion that its symptoms, clinical course, laboratory constellation and pathologic-anatomical findings better correspond to infection-caused toxic-shock syndrome (TSS) than to a toxic-allergic process. PMID- 1861479 TI - Effects of simultaneous training for strength and endurance on upper and lower body strength and running performance. AB - This study examined simultaneous training for strength and endurance during a 13 week, 3-day a week program of hydraulic resistive circuit training and running. Eighteen college males (U.S. Army ROTC) were placed into low resistance (LR; n = 10) or high resistance (HR; n = 8) groups, and 10 college males were controls and did not train. There were 20 exercise stations (7 upper and lower body, and 6 supplementary). LR and HR performed 2 circuits with a work/rest ratio of 20 to 40 s during the 40 min workout. LR trained at two low resistances (approximately 100 cm.s-1), while HR trained at a higher resistance (approximately 50 cm.s-1). Following the workout, subjects ran 2 miles. Pre and post tests included strength, physical fitness, and anthropometry. Strength was assessed with (1) hydraulic resistance dynamometry for 4 exercises at 2 speeds using a computerized dynamometer (Hydra-Fitness, Belton, TX); (2) isokinetic and isotonic upright squat and supine bench press using the Ariel Exerciser (Trabuco Canyon, CA); (3) concentric and eccentric arm flexion/extension at 60 and 120 degrees.s-1 on the Biodex dynamometer (Shirley, NY), and (4) 1-RM free weight concentric and eccentric arm flexion and extension. The fitness tests included 2-mile run, sit ups, and push-ups. Anthropometry included 3 fatfolds, 6 girths, and arm and leg volume. There were no significant changes in body composition or interactions between the fitness test measures and the 2 training groups (p greater than 0.05). Improvements averaged 15% (run time), 30% (push-ups), and 19% (sit-ups; p less than 0.05). Significant improvements also occurred in 3 of 8 measures for hydraulic testing (overall change 8.8%), in 3 of 4 1-RM tests (9.4%), and in 2 of 8 Biodex tests (6%), but no significant changes for isokinetic and isotonic squat and bench press (1.9%). The change in overall strength averaged 6.5% compared to 16% in a prior study that used hydraulic resistive training without concomitant running. We conclude that gains in strength were somewhat compromised by the simultaneous run training, and that improvements in strength and run performance were independent of LR and HR training intensity. PMID- 1861480 TI - The relationship between critical power and the onset of blood lactate accumulation. AB - The purpose of this investigation was to determine the contribution of the onset of blood lactate accumulation (OBLA), the heartrate-workload slope (HR-WL) and the efficiency of electrical activity (EEA = slope of IEMG vs. workload) of the leg extensor muscles to Critical Power (CP). Twelve adult males (mean age +/- SD = 24.5 +/- 2.8 yrs) volunteered as subjects for this study. Zero-order correlations indicated that OBLA was significantly (p less than 0.05) related to CP (r = 0.616) and EEA (r = -0.577). Stepwise multiple regression resulted in a one variable model with OBLA the only significant (p less than 0.05) predictor of CP. Furthermore, a related t-test resulted in a significant difference between the means of the power out-put at CP (mean +/- SD = 230.0 +/- 22.1 watts) and OBLA (179.6 +/- 31.8 watts). The results of this study indicated that the two threshold parameters, CP and OBLA, were significantly related and therefore it is likely that the physiological factors responsible for OBLA also influence CP. However, the significant mean differences indicated that the mechanisms which underly CP and OBLA were not identical. Furthermore, the HR-WL slope (mean +/- SD = 0.343 +/- 0.071 beats per watt) and EEA (0.969 +/- 0.572 microvolts per watt) were not potent predictors of CP. PMID- 1861481 TI - Changes in physical fitness profile during the competitive season in elite bandy players. AB - Nine bandy players from an elite team were used as subjects in order to examine effects of the competitive season on a physical fitness profile. The present findings demonstrated that the competitive season led to a minor change in maximum oxygen uptake (from 63.2 +/- 6.0 to 60.8 +/- 3.7 ml x kg-1 x min-1) but a significant (p less than 0.05) decrease occurred in oxygen uptake at the anaerobic threshold from 48.6 +/- 6.8 to 43.4 +/- 2.3 ml x kg-1 x min-1. Average anaerobic power output during a 60 s maximal work period remained statistically unaltered during the season. A statistically nonsignificant change (from 3233 +/- 493 to 3185 +/- 543 N) took place in maximal strength of the leg extensor muscles. A considerable change occurred during the competitive season in the shape of the isometric force-time curve so that the times of force production lengthened significantly (p less than 0.05) at all positions of the curve. The individual changes during the season in each of the characteristics of the physical fitness profile correlated (p less than 0.05-0.01) with the initial level recorded before the season. The present findings suggest that a competitive season in elite bandy players may lead to considerable decreases in selected characteristics of the physical fitness profile. The findings suggest that the magnitude and/or the frequency of physical training stimuli might be given more attention also during the competitive season and the individual needs of the players should be taken properly into consideration in the full training program. PMID- 1861482 TI - Prediction of maximal heart rate during a submaximal work test. AB - A multiple regression equation was developed utilizing submaximal ratings of perceived exertion and heart rate collected during a treadmill walking test to predict maximal heart rate (MHR). One hundred subjects were administered a modification of the Balke Treadmill test during which time submaximal ratings of perceived exertion (Borg Scale) and heart rate measurements were recorded. Subjects worked until volitional fatigue and maximal heart was recorded. A multiple regression equation was developed which did not require the subject to work at greater than 85% of MHR. The multiple regression equation is MHR = 108.461 + 0.5108 (RPE 15)-0.6570 (8HR) + 0.6075 (10HR)-0.2641 (age in years) with RPE 15 equal to the heart rate at a perceived exertion rating of 15 on the Borg Scale, 8HR equal to the heart rate at 8 minutes and 10HR equal to the heart rate at 10 minutes. It was found that the regression equation significantly improved the ability to predict MHR and represented a 28% improvement in the commonly used equation MHR = 220-age. PMID- 1861483 TI - Increases in aldosterone precede those of cortisol during graded exercise. AB - The purpose of this study was to determine the intensity threshold needed to elicit increases in plasma aldosterone and cortisol during graded exercise in humans. Seven male volunteers performed a maximal oxygen uptake (VO2max) test on a cycle ergometer. Plasma levels of aldosterone, cortisol, angiotensin II, ACTH, and potassium were measured at rest and at each 50 W workload of the exercise test. The results showed that aldosterone significantly (p less than or equal to 0.05) increased from a mean (+/- SE) of 231 +/- 22 pmol/L at rest to 464 +/- 22 pmol/L at exhaustion. Cortisol significantly (p less than or equal to 0.05) increased from 284 +/- 38 nmol/L at rest to 311 +/- 39 nmol/L at exhaustion. More importantly, however, was the fact that aldosterone was significantly increased above the resting level at exercise intensities greater than or equal to 60% VO2max. Cortisol, on the other hand, was only significantly increased at exhaustion (i.e. 100% VO2max). These results clearly show that increases in aldosterone precede those of cortisol during graded exercise in humans. Interestingly, potassium (r = 0.79), ACTH (r = 0.55), and angiotensin II (r = 0.54) were all significantly correlated with aldosterone during exercise. Such a finding seems to suggest that all 3 variables may be important stimuli for aldosterone secretion during graded exercise. PMID- 1861485 TI - Morphological characteristics of elite male field hockey players. AB - The main objective of this paper was to establish a data base of physical norms for elite male field hockey players. Direct measurements were made on eight parameters and a further three derived variables were calculated. With a stature of 176.3 cm and mass of 75.2 kg the hockey players were identified as ecto mesomorphic. The lean build of the subjects was evident with a fairly low percentage body fat (11.1%) and a relatively high RPI of 41.77. Functional arm length did not appear to have any correlation with hockey playing ability. However, grip strength, in both right (54.0 kg) and left (53.1 kg) measures was above that of norms for male adults and there was no significant difference between left and right grip strength. The players appeared to have good leg strength (stand long jump mean 2.3 m) with very little variability amongst the players. On the other hand flexibility (sit and reach mean 9.7) was poor and results indicated a wide range of variability in the sample group tested. PMID- 1861484 TI - The effect of exercise training on body weight and peptide hormone patterns in normal weight college-age men. AB - Resting and peak glucose, insulin, glucagon, gastric inhibitory polypeptide (GIP) and pancreatic polypeptide (PP) levels were evaluated pretraining, 3 weeks and 10 weeks posttraining in seven college age males. The exercise consisted of thrice weekly session of jogging at 70% VO2max for 20 minutes plus warmup and cool down. Following the 10 weeks, VO2max increased significantly. Body weight remained constant and body fat decreased significantly. Fasting and peak blood glucose levels were normal at the beginning of the study yet improved with training. As expected, fasting and peak insulin levels decreased significantly with training. Although GIP did not change significantly with training, an uncoupling of GIP and insulin peak responses was observed. Glucagon levels were essentially unchanged. Fasting and peak PP levels increased slightly as training occurred. These hormone responses suggest that perhaps body weight and/or changes in body fat stores and fuel use might influence peptide hormone responses with training. PMID- 1861486 TI - Energy intake profile in the triathlon competition by means of cluster analysis. AB - The subjects were 18 male triathletes competing in the 4th Kaike Triathlon held at Tottori in 1984. Answers to a questionnaire on dietary and water intake before and during the competition were analysed. Cluster analysis using the average distance method was applied to 21 variables relating to order, age, stature, body weight, total calorie intake and each nutrient element ingested during three periods: after swimming, during cycling and during the marathon. The arrival order was clustered with stature and weight, and its similarity showed 69.7 when the first cluster formed. Age along with carbohydrate, protein or water intake during the marathon formed secondary clusters with order, stature, and weight (similarity: 60.0). In the upper place group, breakfast calories occupied the largest portion of 26.1% and the smallest portion of 17.2% during the marathon running. Furthermore the group ingested more energy than the other groups during cycling. PMID- 1861487 TI - Physical activity and lean body mass loss following coronary artery bypass graft surgery. AB - The present study was undertaken to determine the effect of Phase I exercise therapy on lean body mass loss in recovering coronary artery bypass graft (CABG) surgery patients. Thirty male CABG surgery patients volunteered for the study. Subjects were randomly divided into two groups with one group receiving Phase I exercise therapy. The other group was allowed to participate in ward activities and ad libitum walking. Select measures of lean body mass change, including urinary urea nitrogen, blood urea nitrogen, urinary creatinine, serum creatinine and nitrogen balance, were obtained during six days of hospitalization. Results reveal no statistical difference (p greater than 0.05) between those receiving and those not receiving Phase I exercise therapy relative to these measures. We conclude that the effects of exercise which ameliorate lean body mass loss may be realized by insuring even modest ambulation as an adjunct to frequent assumption of the upright position. PMID- 1861488 TI - Effect of exercise on blood lipid constituents and aerobic capacity of fire fighters. AB - The effect of 32 weeks of exercise training, at moderate intensity, on serum lipids, lipoproteins, aerobic power, anaerobic threshold, body composition, and coronary heart disease (CHD) risk factors was examined in 38 male fire fighters (mean +/- SD 42.7 +/- 6.4 yr). Exercise training included cycling, rowing, walking, jogging, running, and circuit weight training 3 d/wk, 30 min/session at 350 to 450 kcal/session. Fasting blood samples collected pre- and post-training were assayed for triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL C), and high-density lipoprotein (HDL-C). Maximum aerobic power (VO2max) was measured during a treadmill test. Anaerobic threshold (AT) was predicted by observing the onset of a systematic increase in VE/VO2 without a concomitant increase in VE/VCO2. Body composition was determined via underwater weighing and skinfold measurements. There were no significant differences in CHOL, CHOL/HDL-C ratio, or LDL-C/HDL-C ratio. Only the AT, HDL-C, VO2max, and CHD risk levels changed significantly (P less than 0.05). Cholesterol, LDL-C, VLDL-C and triglycerides were linearly related to body fat. Maximal oxygen uptake and HDL-C were inversely related to body fat. It was concluded that moderate exercise intensity can yield a marked increase in AT, VO2max, and HDL-C while not significantly affecting the CHOL level. The findings lend support to the contention that risk reduction for CHD lies on a continuum. PMID- 1861489 TI - A computer-video aided time motion analysis technique for match analysis. AB - The purpose of this study was to find out suitable methods for obtaining objective data on the time spent by players of different positions during walking, jogging, cruising, sprinting and standing still during match play activities. Computer programs and filming analyses with a simple notation system based upon symbolic representations of movements have been devised for analysis of individual players' behaviour. A technique was devised and employed with a small group of university players, aged 19-21 years of age. The subjects were filmed in several matches, and the video recordings were analysed using a microcomputer. The ratio of the time spent for the players were 56% walking, 30% jogging, 4% cruising, 3% sprinting and 7% standing still. ANOVA revealed that there are significant differences among the players for different positions on the field, for example the time spent on walking, jogging and standing still differed (P less than 0.05) among attackers, defenders and midfielders. A new method has been developed to obtain reliable information about the players' movement and performance in the game. The Authors believe that there should be further studies carried out involving more teams at different levels of performance to substantiate these preliminary findings. PMID- 1861490 TI - Relationships among strength, endurance, weight and body fat during three phases of the menstrual cycle. AB - The purpose of this study was to investigate the relationships among body weight, body fat, and dynamic strength and muscular endurance during different phases of the menstrual cycle. Twenty-one female subjects, ages 18-36, with normal menstrual cycles and no dysfunction were tested for strength and endurance of the knee flexors and extensors on a Cybex II isokinetic dynamometer. Body weight and percent body fat were also assessed. Each subject was tested at three speeds (60 degrees, 180 degrees, and 240 degrees/sec) during three phases of the menstrual cycle: mensus (within 24 hours of onset); ovulation (13-14 days from onset); and luteal (10 days from ovulation). The data were analyzed descriptively and by Pearson Product-Moment Correlations with each phase of the cycle and between cycle phases. Results indicated high correlations among most strength measures at the three test speeds for each phase during the cycle and between the cycle phases. Overall, the different phases of the menstrual cycle had little or no effect upon the relationships among body weight, percent body fat, knee extension and flexion strength or endurance. PMID- 1861491 TI - The relationship of maternal exercise on labor, delivery and health of the newborn. AB - Thirty women were interviewed and divided into active and sedentary groups. Pre delivery data, information regarding labor and delivery, Apgar scores of the newborn and perceived exertion during labor were recorded and statistically analyzed. Neonates of active women showed slightly higher one-minute Apgars and no difference in fetal weight or five-minute Apgars. Active women indicated lower perceived exertion during labor, longer delivery times and no differences in gestational length, maternal weight gain and time during the first stage of labor. Maternal weight gain in both groups correlated positively with fetal weight. A higher fetal weight indicated a slightly higher five-minute Apgar. Primaparas showed no difference in the first stage of labor although longer delivery time was noted. No differences in levels of medication during labor were revealed although the youngest and oldest subjects required cesarean delivery. Obese women labored longer, indicated higher perceived exertion and higher fetal weights. PMID- 1861493 TI - Thyroid cancer and multiple primary malignancies in Israel. AB - The exact risk of multiple primary neoplasms in patients with thyroid cancer is difficult to ascertain from the data available in the literature. Three thousand seventy-two patients with thyroid cancer, listed in the Israel Cancer Registry during a 16-year time span, were studied to determine the true incidence of another primary cancer. Ninety-two cases were reported as having an additional primary cancer. The prevalence of multiple primary malignancies was 3%. The frequency was higher among patients of European rather than of Asian or African origin. The second primary cancers in order of decreasing frequency were of the breast, lung, colorectum, head and neck, and lymphoma/myeloma. Most of the deaths were due to the additional cancer. The 5-year survival rate was highest for head and neck and lowest for lung cancer patients. These results emphasize the need for greater awareness of the possibility of developing additional cancers, and indicate the need to incorporate strategies for the prevention, early detection, and treatment of multiple primary neoplasms. PMID- 1861492 TI - Histiocytic neoplasias: immunohistochemical evaluation of their frequencies among malignant lymphoma and related conditions in Japan. AB - Through histologic review of 1,766 cases with malignant lymphoma and related conditions, 35 cases (2%) were selected as probable histiocytic neoplasias. Proliferating cells in these cases had voluminous, granulated cytoplasm, and round to irregularly shaped nuclei often with bi- or multinucleated forms showing monomorphous or polymorphous proliferation accompanying small lymphocytes, plasma cells, and, less frequently, eosinophils. Cases showing proliferation of convoluted cells with numerous benign-appearing histiocytes or large cells with clear cytoplasm were excluded under a diagnosis of T-cell lymphoma. To evaluate the immunologic character of proliferating cells, immunohistochemistry using antibodies Mx-Pan B, MB-1, MT-1, UCHL-1, lysozyme, alpha 1-antitrypsin, alpha 1 antichymotrypsin, S-100 alpha, S-100 beta, Leu M1, epithelial membrane antigen, and Ki-1 were carried out in 23 cases. Naphthol-ASD-chloracetate reaction and toluidine blue stain were also performed. These procedures revealed that 12 cases (52%) were B-cell type, three cases (13%) T-cell type, six cases (26%) true histiocytic type, and two cases null type. Therefore, the frequency of cases with true histiocytic neoplasias among cases with malignant lymphoma and related conditions in Japan may be 0.5%. PMID- 1861494 TI - Parotid manifestations of HIV infection. AB - A lump in the parotid region is generally a salivary tumor unless proved otherwise. Recently with an epidemic of acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC), a large number of pathologies are noticed in the parotid region. These conditions generally involve the intraparotid and periparotid lymph nodes. Hyperplastic lymphadenopathy and the benign lymphoepithelial lesions are the most common variants. Our knowledge regarding these new conditions is just evolving. There remains a therapeutic dilemma starting from observation only to local excision and superficial or total parotidectomy. These lesions must be kept in mind when we evaluate a patient with risk factors for human immunodeficiency virus (HIV) infection. PMID- 1861495 TI - Melanoma tumor vaccine: five-year follow-up. AB - For many years, various melanoma vaccines have been employed. This is a unique melanoma vaccine in that it is a subcellular tumor homogenate and no adjuvants have been added. This vaccine has been given to 129 stage I and 61 stage II melanoma patients. All were followed at least 5 years and had 87.5% and 63.9% 5 year survival rates, respectively. Sixty-four stage I males and 65 stage I females had 84% and 90% 5-year survival rates, respectively. We saw no difference between those with or without lymph node dissection. Thirty-six stage II males and 25 stage II females had 66.7% and 60% 5-year survival rates, respectively. Of stage II patients, 23 had only one positive node, 22 had two to four positive nodes, and 9 had five or more positive nodes with 69%, 63%, and 55% 5-year survival rates, respectively. Large published series were used as historical controls [6,27,28], and significant differences were noted when compared to our stage II patients (P = 0.001)--those with two to four positive nodes (P = 0.03), and those with five or more positive nodes (P = 0.04). We conclude that there is a significant increase in survival for these stage II patients, at high risk of recurrence, receiving a tumor homogenate vaccine. This vaccine warrants further analysis, development, and use in a phase III randomized clinical trial. PMID- 1861496 TI - A myocutaneous flap for closure of upper arm amputations for uncontrolled axillary tumors. AB - Tumor spread or recurrence in the axilla is usually treated with nodal dissections. At times disease recurrence is uncontrolled, causing significant morbidity including pain, bleeding, lymphedema, and neurologic symptoms. Previously, forequarter amputation has been the treatment for this problem, resulting in a significant cosmetic and functional deficit. This report describes a novel myocutaneous flap that can be used to cover soft tissue defects after major disarticulations of the upper extremity. The deltoid myocutaneous flap has been used to successfully treat three patients with uncontrolled tumors in the axilla and preserve the shoulder structures to lessen the functional deficit. PMID- 1861497 TI - Primary breast lymphoma. AB - Primary breast lymphoma (PBL) is a rare tumor of the breast. Three cases of PBL are being described. All three cases achieved remission following biopsy, chemotherapy, and/or radiotherapy. The literature is extensively reviewed with emphasis on true incidence of PBL and survival rates. PMID- 1861498 TI - What's your opinion? KNA members respond to survey. PMID- 1861499 TI - Where do you stand? PMID- 1861500 TI - Nelle Bryant Weller: a Kentucky pioneer nurse (1914-1989). PMID- 1861502 TI - Clinical application of chengshan (UB 57) acupoint. PMID- 1861501 TI - RCT? Care tech? MLP? What is this all about. PMID- 1861503 TI - Treatment of hiccoughs with auriculoacupuncture. PMID- 1861504 TI - Treatment of essential hypertension with auriculoacupressure. AB - Auriculoacupressure was used in the treatment of 291 cases of essential hypertension, in comparison with 51 similar cases treated with Fufang Jiangya (composite hypotensive) Tablets. Analysis of results showed that the therapeutic effects in the 2 groups were similar, while the rate of marked efficacy in the acupressure group was higher than that of the medication group, and the level of blood lipids also significantly dropped (P less than 0.01); there was only minor improvement in blood rheology. In addition, acupressure manifested biphasic regulatory effects on sinus arrythmia. The curative effect of acupressure on essential vascular hypertension was good. PMID- 1861505 TI - Analgesic effect of pressure on auriculoacupoints for postoperative pain in 102 cases. PMID- 1861506 TI - Vertigo treated with scalp acupuncture. PMID- 1861507 TI - The treatment of enuresis with scalp acupuncture. PMID- 1861508 TI - Treatment of primary trigeminal neuralgia with acupuncture in 1500 cases. PMID- 1861509 TI - Treatment of peripheral facial paralysis with pick-prick and connecting acupuncture. PMID- 1861510 TI - Clinical and experimental observations on treatment of peptic ulcer with wei yang an (easing peptic-ulcer) capsule. AB - The therapeutic effects of peptic ulcer treated with cimetidine and Wei Yang An were compared clinically and experimentally by the double blind method. Results showed that the effects of the two are similar, but the long-term effect of Wei Yang An was better. Wei Yang An was also good for most cimetidine resistant ulcers, with few side effect. Animal experiment showed that Wei Yang An inhibited the ulcers. PMID- 1861511 TI - Effects of gynostemma pentaphyllum makino on the immunological function of cancer patients. PMID- 1861513 TI - Treatment of frontal headache with acupuncture on zhongwan--a report of 110 cases. PMID- 1861512 TI - Observation on long-term therapeutic effect in nasopharyngeal carcinoma patients with cyanosis of the tongue after radiotherapy. PMID- 1861514 TI - Treatment of peri-omarthritis with acupuncture at yanglingquan (GB 34). PMID- 1861515 TI - 1291 cases of cholelithiasis treated with electric shock on otoacupoints. AB - Since 1985, the authors began to use electric shock on otoacupoints of varying electric resistance for the treatment of cholelithiasis. The instrument used was the Channel Therapeutic Instrument made in China, and the otoacupoints of varying electric resistance were Sympathetic, Pancreas--Gall Bladder, Stomach, Liver, Sanjiao, Endocrine, and Ermigen. In the 1291 cases treated, the total effective rate was 99.69%, the rate of calculus excretion was 91.32%, and the rate of total excretion was 19.51%. The composition of the calculi was cholesterol crystals (31.25%), bilirubin crystals (28.17%), and mixed crystals (40.58%). The largest calculus excreted was an extrahepatic biliary duct calculus of 1.75 cm X 1.5 cm; the largest number of calculi excreted was 152 cholecystic stones 0.3 cm X 0.5 cm in size. In 100 random cases, the biliary system was shown to manifest vigorous dilations and constrictions under Ultrasonic B-scan when the relevant otoacupoints were stimulated with electric shock. Among the 78 control cases, no cholecystic stones were excreted, inspite of the Magnesium Sulfate, Folium Cassiae and fatty meals administered to many cases with constipation. PMID- 1861516 TI - 97 cases of gastrointestinal spasm treated with moxibustion. PMID- 1861517 TI - Thick needle treatment for periomitis. PMID- 1861519 TI - 302 cases of enuresis treated with acupuncture. PMID- 1861518 TI - TCM treatment of luteal phase defect--an analysis of 60 cases. AB - Sixty cases of infertility due to luteal phase defect were treated with herbs to tonify the kidney and regulate the menstrual cycle. After the treatment, the hyperthermal phase score of basal body temperature (BBT) was markedly increased (P less than 0.05), the hyperthermal phase 7-8 days after ovulation improved (P less than 0.001), the transitional period of BBT remarkably shortened, and the pregnancy rate in 32 uncomplicated cases of luteal phase defect was 56%. The close relationship between luteal phase defect and the kidney deficiency syndrome in TCM was discussed. The key points of the treatment included coordination of yin and yang, regulation of qi and blood, and combination of tonification with reduction. PMID- 1861520 TI - Role of amygdaloid nucleus in the correlation between the heart and the acupoint neiguan in rabbits. AB - Amygdaloid nucleus (AMYG) could converge and integrate the signals from electroacupuncture (EA) at Neiguan (P 6) and acute myocardial ischemia (AMI) in rabbits. And EA could regulate the changes in the discharge of single units in AMYG caused by AMI, that is, EA inhibited the increased frequency, and reversed the decreased frequency. This suggested that AMYG is an important link in correlation between the heart and the acupoint Neiguan, providing an experimental basis for the Theory of Channel--Viscera Correlation. PMID- 1861521 TI - Clinical observations on acupuncture treatment of peripheral facial paralysis aided by infra-red thermography--a preliminary report. AB - We have carried out clinical observations on 34 patients with peripheral facial paralysis treated by acupuncture therapy prescribed according to selection of treatment regimen on the basis of facial thermogram and temperature. A comparison was made with a control group of 97 patients who received conventional acupuncture therapy only. It was found that 1) The cure rate in the group of selecting acupoints by thermogram (hereinafter referred to as the thermography- aided treatment group) was 67.65%, with a marked improvement rate of 26.40%; while the cure rate of the conventional acupuncture treatment group (hereinafter called the conventional treatment group) was 46.39%, the marked improvement rate being 29.90%, indicating a significant difference in therapeutic efficacy between the two groups (P less than 0.02). 2) The average duration of acupuncture therapy for the thermography aided treatment group was 6.02 weeks, whereas that for the conventional treatment group, 24 weeks. There was also a significant difference between the two groups (P less than 0.01). And 3) During the entire therapeutic course, 25.2 sessions of treatment were given on the average in the thermography- aided treatment group, and 78.8 sessions in the conventional treatment group, showing a very significant difference (P less than 0.001). The present thermography--aided method exhibits advantages over the conventional one in enhancing the cure rate and shortening the duration of treatment, which is worthy to be popularized in clinical practice. And it is also of certain significance in standardization and scientification of acupuncture therapy. PMID- 1861522 TI - What are the commonly-used acupuncturing methods for abstinence from smoking? PMID- 1861523 TI - Research on "anti-aging" effect of qigong. PMID- 1861524 TI - Diagnosis and treatment of apoplexy. PMID- 1861525 TI - Trial treatment of AIDS by TCM--a clinical report of 30 cases. PMID- 1861526 TI - Treatment of chronic coronary insufficiency with acupuncture on ximen point. PMID- 1861527 TI - Mechanisms of differentiation of U937 leukemic cells induced by GM-CSF and 1,25(OH)2 vitamin D3. AB - The human monoblast cell line, U937, was employed to elucidate early events associated with differentiation induced by granulocyte-macrophage colony stimulating factor (GM-CSF) and 1,25-dihydroxy-Vitamin D3 (VD3). Exposure of cells to a combination of GM-CSF and VD3 resulted in an up-regulation of c-fos mRNA within 1 h and a marked down-regulation of c-myc mRNA by 24 h and this was associated with a shift of cell population from the S phase to the G0 + G1 phase of the cell cycle by 18%. This was followed by a marked enhancement of monocyte associated cell surface antigens [OKM1 (CD11b), LeuM3 (CD14), M77.7], as determined by monoclonal antibodies and flow cytometry. Functional characteristics such as nitroblue-tetrazolium reduction, alpha-naphthyl butyrate esterase activity, and phagocytic capability occurred. Cells treated with GM-CSF or VD3 alone showed only minor changes. These results demonstrate a potent synergistic effect of GM-CSF and VD3 on induction of U937 differentiation. This differentiation was partially blocked by H7, a protein kinase C (PKC) inhibitor. Changes in c-myc and c-fos mRNA expressions and a shift in cell cycle were shown to be early events in this process. PMID- 1861528 TI - Should alpha interferon be used as primary treatment for hairy cell leukemia? Italian Cooperative Group for Hairy Cell Leukemia. AB - To answer the question of whether interferon (IFN) should replace splenectomy, we reviewed the Italian HCL Registry: the records of 450 patients with hairy cell leukemia (HCL), seen from 1975 to 1988 were analysed. Of these, 321 were considered for the study: 231 had been splenectomized, 46 of them receiving subsequently IFN and 90 patients had IFN as initial therapy. Patients treated with splenectomy showed different survival according to Jansen and Hermans' staging system, which identified two risk groups: stage 1 and stages 2 and 3, p = 0.0329. On the contrary, patients treated with IFN did not show significantly different survival according to stage. By the comparison of stage 1 patients, either treated with splenectomy or with IFN, no statistical difference in survival was registered. Different survivals emerged for patients stage 2 + 3, which improved when treated with IFN, p = 0.0324. The median failure free survival (FFS) after splenectomy resulted in 89 months versus 33 months after IFN. In conclusion, splenectomy still remains the primary therapy for HCL patients stage 1. For high risk patients, stages 2 and 3, IFN should be adopted as first line therapy, improving substantially the survival. The short duration of response to IFN suggests a sequential combination of the two treatments for this group of patients, IFN reducing tumor mass quite safely and splenectomy assuring long lasting stable disease. PMID- 1861530 TI - Continuous intravenous infusion of high dose recombinant interleukin 2 for advanced lymphomas--a phase II study. AB - The prognosis of patients with advanced refractory lymphoma remains poor. We have carried out a Phase II study of continuous high dose intravenous recombinant interleukin 2 alone without LAK cells in this group of patients. Eight patients have so far been treated, 4 with non-Hodgkins lymphoma and 4 with Hodgkins disease. Of the 7 evaluable patients, the maximum response observed was stable disease in 2 patients (1 with NHL and 1 with HD). The other patients' diseases progressed in the face of immune activation following the rIL-2 infusion. Adverse reactions were common but no life-threatening occurred. These results are disappointing. Whether or not lymphokine-activated killer (LAK) cells are needed to improve response rate deserve further investigations. PMID- 1861529 TI - Expression of an oncofetal protein (OFP) in rat and human leukemia cells. AB - A unique oncofetal protein (OFP) previously identified in rat fetal tissue and rat and human solid tumors, is now shown to be present in rat and human leukemia cells by use of a monoclonal antibody-based assay. Using a highly specific anti rat OFP monoclonal antibody OFP has been unquivocally immunolocalized to the cytoplasm of the rat leukemia cells. The factor is rapidly released to the circulation as 50 and 55 kD species which share the immunological determinants. When leukemia cells are transplanted to normal rats, OFP increases in the circulation in a biphasic manner which may be due to immune clearance since circulating anti-OFP antibodies have been demonstrated. Induction of differentiation in the human HL-60 leukemia cell line by 13-cis-retinoic acid caused a down regulation of OFP synthesis, both intra- and extra-cellular levels dropping to essentially zero. Induction of differentiation with dibutyryl cyclic AMP caused a cessation of secretion of OFP, with a marked increase in its intracellular concentration, a condition resembling the retention in fetal cells. Leukemia cells add to a growing list of tumors previously shown to produce OFP, suggesting that OFP is intimately involved in some facet of tumorigenesis. PMID- 1861531 TI - CD9 antigen on acute non-lymphoid leukemia cells: preferential expression by promyelocytic (M3) subtype. AB - A monoclonal antibody (S17-12), previously described to recognize subsets of myelomonocytic cells, is demonstrated to bind CD9 antigen, a surface marker of B cell precursors, platelets and several non-hematopoietic tissues. The proportion of S17-12, CD9-positive leukemic cells was determined in 102 patients with acute non-lymphocytic leukemia. It was found to be above 75% in 14/22 M3 cases (including 3/3 of microgranular variant) and only in 1/80 cases of different FAB subtype. Complete reactivity (greater than 95%) of leukemic clonogenic cells with CD9 MoAB was restricted to 4/18 M3 cases. Therefore, a high proportion of CD9 positive cells seems to be peculiar to M3 cases. This may help in the diagnosis of cases that lack typical morphological features. PMID- 1861532 TI - Pharmacological studies of retinol palmitate and its clinical effect in patients with acute non-lymphocytic leukemia. AB - The pharmacokinetics of retinol palmitate were studied, and a therapeutic trial was performed in patients with ANLL. In the pharmacokinetics study, retinol was the only metabolite that was detected in plasma, and the peak concentration was 332 micrograms/dl (about 1.2 x 10(-5) M) 2.1 h after administration of retinol palmitate. Five patients with ANLL (4 with ANLL-M3 and one with ANLL-M2) were treated with retinol palmitate. In all patients with ANLL-M3, bone marrow suspension culture studies revealed that retinol induced both morphological and functional differentiation of immature leukemic cells. During the course of the treatment with retinol palmitate, morphological differentiation of bone marrow immature leukemic cells was observed in all patients with ANLL-M3 within 3-4 days after initiation of the therapy. In three of the four patients who underwent conventional chemotherapy, the sequential treatment with retinol palmitate resulted in a complete remission: controlling residual bone marrow leukemic cells. None of the patients showed any signs of aggravation of DIC in the coagulation parameters. These findings suggest the possibility that retinol palmitate functions as salvage therapy by inducing maturation and slowing proliferation, there by clearing out the residual leukemic cells following conventional chemotherapy. PMID- 1861533 TI - Monitoring the unmaintained remission of acute non-lymphoblastic leukemia by serial bone marrow cultures. AB - Between 1974 and 1989, 217 patients with ANLL, aged less than 70 years, were submitted to an intensive remission induction chemotherapy. A complete remission was achieved in 100 (46%) cases. Ten (10%) patients survived in continuous remission beyond 16 months after cessation of remission maintenance therapy. In these 10 long-term survivors, bone marrow was serially cultured in semi-solid agar during the unmaintained remission for a median period of 40 (range 12-72) months. In another group of 18 patients bone marrow was cultured after cessation of remission maintenance chemotherapy at intervals of 29-43 (median 33) days until relapse, at most up to 16 months, when all patients relapsed. In both groups of patients a periodic return to a leukemic growth pattern in their marrow cultures was observed. The difference in the frequency of leukemic growth patterns between both groups is not significant, while the patients, who remained in prolonged remission, had a significantly higher mean number of colonies. It is suggested that monitoring the remission with the help of bone marrow cultures is useless in predicting an approaching relapse of ANLL. However, a high number of colonies in most marrow cultures is perhaps an indicator of a prolonged remission. PMID- 1861535 TI - High efficacy of monomethoxypolyethylene glycol-conjugated L-asparaginase (PEG2 ASP) in two patients with hematological malignancies. AB - Two patients with hematological malignancies were successfully treated with monomethoxypolyethylene glycol-conjugated Escherichia coli L-asparaginase (PEG2 ASP), which reportedly lacks both antigenicity and immunogenicity but retains catalytic activity as well as slow clearance in an experimental animal model. A 20-year-old male patient with leukemic lymphoma was refractory to conventional chemotherapy but responsive to L-asparaginase (L-ASP) followed, however, by severe adverse effects. On relapse, an intravenous infusion of 100-200 IU/day dose of PEG2-ASP alone led to a complete remission 2 months later without hypersensitivity or other significant adverse reactions. Surprisingly, he remained in a complete remission for over one year with a regular weekly infusion of PEG2-ASP, combined with a weekly small dose of Ara-C. During this period, blood asparagine was not detectable. The other patient, a 64-year-old woman with chronic myelogenous leukemia in blast crisis achieved, within 6 weeks, a complete remission with twice-weekly infusions of PEG2-ASP. Thus, PEG2-ASP is a highly effective antitumor agent overcoming the limitations in therapeutic use of L-ASP. PMID- 1861534 TI - Distinct patterns of sulfated proteoglycan biosynthesis in human monocytes, granulocytes and myeloid leukemic cells. AB - The production of sulfated proteoglycans was compared in mature peripheral blood granulocytes and monocytes and HL-60 promyelocytic leukemia cells. We found that HL-60 cells synthesized 5-10 times more proteoglycans than peripheral blood leukocytes. Differentiation of HL-60 cells toward mature monocytes by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or towards granulocytes by treatment with retinoic acid or dibutyryl cyclic adenosine-3',5'-monophosphate (dbcAMP) resulted in a small (20-30%) decrease in sulfated proteoglycan biosynthesis. Chondroitin sulfate was found to be the predominant proteoglycan produced by monocytes, PMN and undifferentiated HL-60 cells. Differentiated HL-60 cells produced chondroitin sulfate as well as sulfated proteoglycans sensitive to nitrous acid degradation. Similar results were observed in TPA, dbcAMP and retinoic acid differentiated HL-60 cells indicating that the changes in proteoglycan biosynthesis observed were independent of the developmental pathway. Using specific monoclonal antibodies and flow cytometry, we also found that HL-60 cells and monocytes produced chondroitin-4-sulfate, chondroitin-6-sulfate and chondroitin-O-sulfate while PMN only produced chondroitin-4-sulfate. In addition, although there were no significant differences in antibody binding to undifferentiated and differentiated HL-60 cells, the tumor cells bound 5-20 times more of the antibodies than the peripheral blood leukocytes. Our data demonstrate that sulfated proteoglycan production by HL-60 cells is distinct from PMN and monocytes. In addition, the fact that differentiated HL-60 cells continue to synthesize larger amounts of the proteoglycans than the peripheral blood leukocytes indicates these cells have not completely matured. PMID- 1861536 TI - Transient expression of trisomy 21 and monosomy 7 following cyclosporin A in a patient with aplastic anemia. AB - We present a patient with severe idiopathic aplastic anemia with no previous chromosomal abnormalities who developed trisomy 21 and monosomy 7 during treatment with intravenous (i.v.) cyclosporine. The abnormal karyotype disappeared when the drug was changed to the oral form. This cytogenetic aberration, previously unreported in association with cyclosporine, may reflect either a direct drug effect or the emergence of a hidden myelodysplastic cell clone subject to preferential survival during immunosuppression. PMID- 1861537 TI - Differentiation of myeloid leukemic cells induced by high-dose methylprednisolone in patients with acute myeloblastic leukemia and its therapeutic potential. PMID- 1861538 TI - Simple immuno bead labeling of leukemic cell clusters cultured in methylcellulose. AB - In studies of in vitro leukemic clonogenic cells it is of importance to determine the cell lineage of individual clusters grown in culture. A method is described for the in-situ identification of leukemic cell clusters in methylcellulose cultures. Whole cultures are dried and incubated with various monoclonal antibodies, followed by incubation with beads coated with secondary antibody. Clusters containing antibody-positive cells are heavily labeled with beads which simplifies the recognition and scoring of clusters using normal light microscopy. This method has general applications and can also be used to identify normal myeloid and lymphoid clusters depending on the availability of lineage specific monoclonal antibodies. PMID- 1861539 TI - In vitro chemosensitivity testing in chronic lymphocytic leukaemia patients. AB - Twenty-nine samples from eighteen patients with chronic lymphocytic leukaemia (CLL) were used in a direct comparison of in vitro response to chlorambucil measured in a metabolic (MTT) and dye exclusion (D.Ex) assay. Reduced ability to produce formazan corresponded to a reduced number of dye-excluding viable cells and a significant correlation was found between dose-response measured in the two assays. Initial low absorbance values obtained with untreated control cells in the MTT assay were effectively overcome by increasing both the cell seeding density and MTT exposure time with the consequent increase in assay sensitivity. The MTT assay provided qualitatively similar dose-response data to that obtained in the D.Ex assay. A wide range in in vitro response was seen for both pretreatment and treatment patient groups. In vitro dose-responses were seen to coincide with decreasing or stable white cell counts, taken around the time of sampling, in samples from 4 patients. Less marked dose-responses were observed for 2 patients considered clinically resistant to chlorambucil. The MTT assay would seem, therefore, to be applicable to in vitro assay of cell response in CLL. PMID- 1861540 TI - Serum erythropoietin concentrations in patients with myelodysplastic syndromes. AB - Medullary dyserythropoiesis with reduced production of erythrocytes is an early and consistent feature of myelodysplastic syndromes (MDS). The mechanism underlying the disturbed red cell proliferation and maturation is presently unknown. In order to study the role of erythropoietic growth factors, we determined by radioimmunoassay the serum concentrations of immunoreactive erythropoietin (Epo) in 42 non-transfused patients with primary and secondary MDS. Their median hemoglobin concentration at the time of Epo measurement was 9.1 g/dl (range, 5.7-14.6). Compared with the control group, 83% of the MDS patients had increased serum Epo levels, ranging from 26-4530 mU/ml. Although in the entire patient population an inverse relationship between serum Epo and hemoglobin concentrations was noted (r = -0.35; p = 0.02), Epo titers differed markedly between patients at comparable degrees of anemia. In 7 patients presenting with a hemoglobin concentration between 5.9 and 11.9 g/dl, excessive elevations of Epo levels (greater than 500 mU/ml) were found. In contrast to previous observations, serum Epo concentrations were not shown to correlate with the percentage of erythroblasts in the bone marrow. There was, however, a significant relationship between the Epo activity and the degree of medullary dyserythropoiesis, as assessed by morphological criteria (p less than 0.01). From these data we conclude that the anemia in MDS is not due to an endogenous Epo deficiency. The marked variability of Epo production in these disorders is not fully explained by the degree of anemia, but may also reflect inherent abnormalities of the myelodysplastic erythropoiesis. PMID- 1861541 TI - Simplified quantitative estimation in vitro of lymphocyte radiosensitivity applied to patients with chronic lymphocytic leukaemia. AB - Lymphocyte survival changes observed at 1, 2 and 3 days as responses to 3 doses of ionising radiation in vitro (40, 100, and 500 cGy) are analysed by computer according to a simple (single cell population) mathematical model. Intrinsic radiosensitivity, the susceptibility to lethal injury, which is expressed as the D37 value (the radiation dose permitting 37% survival), is estimated separately from the kinetics of subsequent death of lethally-irradiated cells (expressed as their half-life, or t1/2 value). Among the 35 patients with B-cell CLL studied (15 were never treated), both parameters varied widely and independently of one another. t1/2 ranged from 9-200 h and above, D37 from 14-500 cGy or above. Twenty three patients were deemed 'radiosensitive' (D37 below 110 cGy). D37 level did not correlate with treatment status, mode of treatment, clinical staging (Rai) or lymphocyte count. With some exceptions, D37 remained relatively constant for individual patients with increasing duration of disease or alterations in treatment status. The assay method may prove useful as an aid in predicting response to low-dose splenic irradiation (SI) in CLL. PMID- 1861542 TI - Impaired expression of interleukin 2 receptors in childhood acute lymphoblastic leukemia. AB - Peripheral blood mononuclear cells (PBMC) from acute lymphoblastic leukemia (ALL) patients were studied for the expression of interleukin 2 receptors (IL-2R). When stimulated with phytohemagglutinin (PHA) for 3 days, the percentage of p55 Tac positive cells and the number of high affinity IL-2R was decreased in on-therapy ALL patients at remission and returned to normal after cessation of the treatment. However, the percentage of p75 IL-2R positive PBMC was normal in all ALL patients at remission. It is well-known that there are several immunological abnormalities including T and natural killer (NK) cell dysfunctions in ALL patients undergoing maintenance chemotherapy. IL-2 facilitates T-cell growth and corrects defective NK activity. Taking this into account, there may be a poor utilization of autologously produced IL-2 because of the impaired expression of IL-2R, and this poor utilization of IL-2 may be related to the defective immunological functions in childhood ALL patients at remission who are receiving maintenance chemotherapy. PMID- 1861543 TI - IL-2-dependent ATL cell lines with phenotypes differing from the original leukemia cells. AB - Adult T-cell leukemia (ATL) cells have been shown to express the receptor for IL 2 by studies using anti-CD25 monoclonal antibody, but these cells usually show no or only a weak proliferative response to IL-2. In the present study, we established thirteen IL-2-dependent T-cell lines from four ATL patients. Examination of the clonalities of these cell lines by the rearrangement profiles of the TCR beta-chain gene and the integration sites of the HTLV-I proviral genome, revealed that two cell lines (KK-1 and KK-5) were of real ATL cell origin. The others were of normal T-cell origin and had been established by infection with HTLV-I. The KK-1 and KK-5 cell lines were derived from a single ATL patient (KK). Interestingly, these cells showed different phenotypic features from the majority of original leukemia cells (CD3 +/- CD4+ CD8-). The KK-1 cell line acquired CD8 antigen expression and became double-positive (CD3 +/- CD4+ CD8+), while the KK-5 cell line prominently expressed CD3 antigen (CD3+ CD4+ CD8 ). These results indicate that the phenotypic feature of ATL cells are not fixed, but can change in vitro as has occasionally been observed in vivo. PMID- 1861544 TI - Abnormal localization of immature precursors (ALIP) in the bone marrow of myelodysplastic syndromes: current state of knowledge and future directions. AB - It has been suggested that the occurrence of abnormal localization of immature precursors (ALIP) in the bone marrow biopsy (BMB) may be of diagnostic and prognostic significance in myelodysplastic syndromes (MDS). The recognition of ALIP has been based exclusively on bone marrow histological appearances. During the last decade technical advances have led to the widespread use of various immunophenotypic markers for the diagnostic and prognostic purposes which has contributed enormously in understanding the development of haemopoietic cells and the cellular origin of various haematological malignancies. In addition proliferation antigens, growth factors, oncogenes, anti-oncogenes and other biological discoveries have opened new vistas to our knowledge of the normal and neoplastic growth processes. Despite this, the precise nature of ALIP and their significance in relation to the aetiopathogenesis and evolution of MDS remains unclear. Indeed the diagnostic value of ALIP in MDS is debatable. Furthermore, the precise cell lineages which comprise ALIP are not defined. The purpose of this review is to address these issues and to incorporate our new findings on the histological and immunophenotypic characterization of immature cell aggregates. PMID- 1861545 TI - Cellular cytotoxic function and potential in acute myelogenous leukaemia. AB - Twenty-seven adult AML patients (13 with active disease and 14 in complete remission) were investigated for their cellular cytotoxic potential and function. All AML patients, whether with active disease or in complete remission, showed increased percentage of CD3+ lymphocytes expressing the cytotoxicity-linked cytoplasmic serine esterase, suggesting a higher than normal cytotoxic potential. However, when the cytotoxic function in these patients were analysed in terms of the natural killer and lectin-dependent cellular cytotoxicity, all AML patients, whether with active disease or in complete remission, had impaired target cell lytic activity. This paradox of cytotoxicity is most likely due to the immunosuppressive effect of the serum factor elaborated by leukaemia myeloblasts. PMID- 1861546 TI - Effect of (dl)-5-methyltetrahydrofolate on lymphoid leukemia cell lines. AB - We studied the effect of (dl)-5-methyltetrahydrofolate (mTHF) on the lymphoid cell lines BALM 3, CCRF-SB, CEM, Daudi, MOLT 4 and P3HR1, employing doses in the mM range. The growth of all the lines studied was inhibited by mTHF in a dose dependent fashion. mTHF demonstrated a substantial cytocidal effect on leukemic lymphoid cells of up to 3 log, as measured by limiting dilution analysis, at a concentration of 10(-3) M. At this dose normal human lymphocyte viability was not affected, and their mitogen-induced proliferation was only slightly impaired. We tested the effect of high doses of mTHF on a clone of CEM cells (CEM-MTXr) infected with the pSDHT retrovirus able to transduce a dominant-acting gene encoding a mutant, less efficient, dihydrofolate reductase. CEM-MTXr cells were inhibited by high doses of mTHF to the same degree as the parental line, thus suggesting that the enzymatic reactions leading to folate reduction are not involved in the cytocidal effect of mTHF. PMID- 1861547 TI - Mosaic 46,XY/92,XXYY,del(5)(q13 q34) in an adult lymphoblastic leukemia. AB - Usually the chromosome anomalies encountered in ALL are modal number abnormalities (hyperdiploidy or hypodiploidy) and structural anomalies such as t(8;14), t(11;14), t(9;22), t(1;19) and del(6p). The 5q- syndrome is mainly associated with myelodysplastic syndromes and with ANLL (M1, M2, M3). We report the case of a patient presenting with a mosaic karyotype 46,XY/92,XXYY,del(5)(q13 q34) in the following proportion 1/3 normal mitoses and 2/3 tetraploid mitoses. PMID- 1861548 TI - Prospective evaluation of vertical banded gastroplasty as the primary operation for morbid obesity. AB - Our previous experience with vertical (nonbanded) gastroplasty proved disappointing because of unsatisfactory maintenance of weight loss. Vertical banded gastroplasty seemed to be an attractive alternative operation because it provided an externally reinforced (banded) stoma that would not enlarge over time. In this study, our aim was to determine prospectively the results of vertical banded gastroplasty used as a primary, weight-reducing procedure in patients with morbid obesity. Seventy consecutive patients with morbid obesity (mean weight, 139 kg), all of whom had obesity-related complications, underwent vertical banded gastroplasty and prospective follow-up. The hospital mortality was nil, and substantial morbidity occurred in 3% (two patients). Long-term achievement and maintenance of satisfactory weight loss, however, were variable. The median weight loss at 1 year after operation was 36.7 kg or 48% of excess body weight. At 3 years postoperatively, however, weight loss was only 32.4 kg or 40% of excess body weight, and only 38% of patients had achieved and maintained a weight loss of 50% or more of their preoperative excess body weight. Vertical banded gastroplasty caused major changes in eating habits, and many patients were unable to eat red meat or untoasted bread; moreover, approximately 30 to 50% of patients continued to vomit once or more per week. Despite theoretically attractive advantages as a weight-reduction operation, vertical banded gastroplasty does not seem to be the optimal procedure for most patients with morbid obesity. PMID- 1861549 TI - Associative anomia: dissociating words and their definitions. AB - A 60-year-old woman, in whom magnetic resonance imaging and single photon emission computed tomography confirmed the presence of chronic damage to the left temporal lobe, had pure anomia with sparing of other language and cognitive functions. She could independently access lexical knowledge (words) and semantic knowledge (word definitions). We postulate that her anomia was due to a failure to associate lexical and semantic knowledge. PMID- 1861550 TI - Causes of death in patients with tuberous sclerosis. AB - Of the 355 patients with tuberous sclerosis complex (TSC) examined at the Mayo Clinic, 49 had died (9 of causes other than TSC). We attempted to determine what pattern of organ involvement occurred most often in the 40 patients who died of TSC. One baby died of cardiac failure due to cardiac rhabdomyomas, and one child died of rupture of an aneurysm of the thoracic aorta. Eleven patients died of renal disease, which was the commonest cause of death. Ten patients died as a result of brain tumors, and four patients (who were 40 years of age or older) died of lymphangiomyomatosis of the lung. Thirteen patients with severe mental handicaps died of either status epilepticus or bronchopneumonia; in all but one of these patients, the only source of information was the death certificate. Survival curves show a decreased survival for patients with TSC in comparison with that for the general population. Patients with TSC need lifelong follow-up for early detection of potentially life-threatening complications. PMID- 1861551 TI - Sensitivity to vasovagal maneuvers in normal children and adults. AB - In 15 male and 15 female healthy subjects who were 10 to 48 years of age, we studied alterations in heart rate and finger blood flow in response to the cold pressor test and four strong vasovagal maneuvers: diving response (apneic facial exposure to an ice water bag), Valsalva maneuver (forced expiration against a column of mercury to 40 to 50 mm Hg), unilateral carotid sinus massage, and oculocardiac reflex (inflation of a Honan balloon against one eye). Peripheral vasoconstriction as a consequence of the diving response paralleled the vasoconstriction from the cold pressor test, but it preceded the bradycardia that resulted from the diving response maneuver. In contrast, the rate of finger blood flow was high during the bradycardia that followed stage 4 of the Valsalva maneuver. Changes in heart rate correlated with age for the diving response, the Valsalva maneuver, and the oculocardiac reflex. Changes in heart rate and finger blood flow were not dependent on sex. The change in heart rate noted with the diving response was significantly correlated with that noted with the Valsalva maneuver and the oculocardiac reflex. Changes in finger blood flow did not correlate with changes in heart rate for any maneuver. This study provides a response profile of relative sensitivities to strong vasovagal maneuvers in normal children and adults. PMID- 1861552 TI - Systemic adjuvant therapy in women with resected node-negative breast cancer. AB - Currently, the role of adjuvant systemic therapy in women with node-negative breast cancer is being determined. Several studies of adjuvant hormonal therapy and adjuvant chemotherapy have demonstrated a moderate reduction in the risk of recurrence in the treated patients. With relatively limited follow-up, however, overall survival has not improved with use of adjuvant therapy. The use of prognostic factors to select those patients at highest risk for relapse is an active area of oncologic research. The decision to recommend adjuvant therapy necessitates assessment of the probability of recurrence, the expected reduction of risk with adjuvant therapy, the toxic effects of therapy, and the influence of treatment on the patient's overall quality of life. PMID- 1861553 TI - The influence of politics in the medical community. PMID- 1861554 TI - Wojciech Oczko--famous Polish physician. PMID- 1861556 TI - Vertical banded gastroplasty in the treatment of severe obesity. PMID- 1861555 TI - The porcine model for the understanding of thrombogenesis and atherogenesis. AB - The hypothesis originated by Carl Rokitansky a century ago that thrombosis contributes substantially to atherosclerosis has been rekindled by accumulating experimental and clinical evidence. On the basis of our experience with the experimental porcine model, several important biologic determinants of thrombosis have been identified. The degree of vascular injury seems to be the primary determinant of the thrombotic response. In addition, hemodynamic shear stress and the presence of the von Willebrand factor have important roles in the process of thrombosis. Although there is little evidence that thrombosis is a factor in the initiation of spontaneous, or naturally occurring, atherosclerosis, substantial evidence suggests that thrombosis has an essential role in the progression of spontaneous atherosclerosis and also in the early pathogenic process of the syndromes of accelerated atherosclerosis-namely, heart transplant atherosclerosis, vein graft disease, and coronary restenosis after angioplasty. Advances in the understanding of vascular injury and of the interactions of blood cells with the vascular wall have allowed development of new experimental antithrombotic strategies and subsequent clinical applications in the prevention of these vascular diseases. PMID- 1861557 TI - What's in a name? PMID- 1861558 TI - Tuberous sclerosis. PMID- 1861559 TI - Mechanism of CW Nd:YAG laser recanalization with modified fiber tips: influence of temperature and axial force on tissue penetration in vitro. AB - Modified fiber tips are used for laser angioplasty of totally occluded peripheral arteries. It has not been established, however, to what extent the mechanism of action of various laser probes is optical, thermal, or mechanical. We examined transparant contact probes (hemispherical contact probes and ball-shaped fibers) and metal laser probes, coupled to a continuous-wave Nd-YAG laser. By using homogeneous thick porcine fatty tissue samples submerged in blood plasma, tissue penetration was measured in relation to the temperature of the probe and the axial force exerted on the tissue. By using 15 W, 1 s laser pulses, the surface of transparent contact probes had to be first contaminated by carbonized tissue particles to achieve tissue penetration. Penetration increased from 1 to 10 mm per pulse when axial force increased from 20 to 100 g. Metal probes had to be sufficiently insulated from the liquid environment by water vapour entrapped in a denatured protein layer to exceed the threshold temperature of 225 degrees C for tissue penetration. When axial force increased from 20 to 80 g at 10 W continuous exposure, the velocity of tissue penetration increased in the range from 1 to 4 mm/s. Tissue penetration by modified fiber tips is attributed to both remodeling and vaporization of tissue. With transparent contact probes, tissue is heated partly by direct light absorption and partly by a hot probe surface. Axially directed force is necessary to displace lateral non-ablated tissue and to overcome mechanical resistance. We conclude that mechanical dilation due to axial catherization force (Dotter effect) contributes substantially to tissue penetration by transparent contact probes. PMID- 1861560 TI - Temperature along the surface of modified fiber tips for Nd:YAG laser angioplasty. AB - For laser angioplasty probes, the thermal properties of the probes will primarily determine their mechanism of action. We examined the absorption, temperature increase, and probe degradation of transparent contact probes (hemispherical contact probe and ball-shaped fibers) and metal laser probes coupled to a continuous-wave Nd-YAG laser. Temperature was recorded by means of thermocouples and the measurements were corrected for direct light absorption by the thermocouple. During 15 W, 1 s exposure, the peak temperature rise of the hemispherical contact probe in contact with tissue dropped from approximately 1,000 degrees C at the front end to below 45 degrees C (95% drop) at the lateral side. In contrast, during continuous exposure the peak temperature rise of metal laser probes in contact with tissue dropped from 560 degrees C at the front end to near 400 degrees C (30% drop) at the 5.5 mm proximal rear end. During exposure in blood or tissue, the transparent contact probes became contaminated. Their absorption increased from 5 to 33% and the probe deteriorated. Repeated use of metal laser probes in blood resulted in a higher temperature at the rear than at the front end due to backburing of the fiber. Owing to the large temperature drop along the surface of transparent contact probes, the area of thermal destruction is limited to the tissue in front of the probe, whereas along the entire surface of metal laser probes the tissue will be affected. The large difference between these temperature distributions should be respected during clinical application of the transparent contact probe and the metal laser probe. PMID- 1861561 TI - Argon laser-assisted anastomoses in medium-size vessels: one-year follow-up. AB - Laser-assisted anastomosis of medium-size vessels can be performed with satisfactory short-term patency. This study was undertaken to evaluate patency and structural integrity up to 1 year. An argon laser was used to make bilateral femoral arteriovenous anastomoses in 12 dogs compared to conventional suture method in another 8 dogs. These anastomoses were evaluated for patency and aneurysm formation at 1 hour; 1, 2, 4, and 8 weeks; and 12 months after surgery. All anastomotic sites were patent and without aneurysmal change or luminal narrowing at all harvesting intervals. Histologic examination revealed that within 1 month laser anastomotic sites were almost completely healed and without intimal hyperplasia. In suture anastomoses, foreign-body reaction remained evident up to 1 year. Use of the argon laser for medium size vessel anastomoses resulted in excellent patency without aneurysm formation or intimal hyperplasia even in the long term. These data suggest promising clinical applications. PMID- 1861562 TI - Potential use of holmium lasers for angioplasty: evaluation of a new solid-state laser for ablation of atherosclerotic plaque. AB - Tissue effects of the mid-IR Holmium laser (emitting at a wave-length of 2130 nm) were evaluated. This wavelength is attractive because it combines high water absorption and easy transmission through standard optical fibres. The laser was pulsed with pulse durations in the range of 100 microseconds and repetition rates between 2 and 6 Hertz. For all experiments a repetition rate of 2 Hertz was used. The laser beam was coupled into waterfree quartz fibers with core diameters of 200 and 800 microns with an efficiency of 70 and 80%, respectively. Ablation of atherosclerotic plaque has been performed at an ablation threshold of 10J/cm2 for the 800 microns and 40J/cm2 for the 200 microns fibre. Removal of calcified plaque was possible. Ablation efficiency increased in a non-linear fashion with increasing pulse energies. The ablation rate per pulse was approximately 2 mm at energy fluences of 1000J/cm2 for the 200 microns fibre and 1.25 mm at energy fluences of 70J/cm2 for the 800 microns fibre; a further increase in energy densities did not result in higher ablation rates. On macroscopic examination only very limited thermal injury was found in crater adjacent tissue structures. Crater edges were even and did not reveal signs of crater charring or debris in the crater lumen. However, the histologic specimens revealed zones of thermal damage extending 100 up to 1000 microns lateral into adjacent tissue. Thermal damage increased with increasing radiant exposures and depended on the medium used. PMID- 1861563 TI - Wavelength dependence of pulsed laser ablation of calcified tissue. AB - Pulsed laser ablation of calcified biological tissue was studied at several wavelengths in the near-ultraviolet, visible, near- and mid-infrared regions of the spectrum. The primary tissue model was bovine shank bone, while human arterial calcified plaque and normal human artery wall were also studied at selected wavelengths for comparison. Laser irradiances were on the order of MW/mm2, fluences ranged up to 1000 mJ/mm2, and repetition rates varied between 0.3-10 Hz. Spot sizes on the tissue surface ranged from 150 to 850 microns. Laser craters made with wavelengths between lambda = 295 nm and lambda = 375 nm and in the lambda = 3 microns region exhibited the highest quality ablation with clean, sharp cuts following closely the spatial contour of the incident beam. Craters drilled with visible wavelengths between lambda = 450 nm and lambda = 590 nm were generally larger than the incident laser beam spot, irregular in shape and often surrounded by large flakes of tissue debris. Ablation fluence thresholds increased with wavelength through the visible wavelengths and into the mid infrared, but dropped to their lowest values near lambda = 3 microns. Fluence thresholds obtained with the tissue under a 1 mm depth of saline were approximately twice air thresholds. Ablation yields also varied with wavelength, probably due to increased scattering in the visible region, and were the same under saline as in air. PMID- 1861564 TI - Argon laser initiated resin photopolymerization for the filling of root canals in human teeth. AB - This work was undertaken to determine if 488 nm light is transmitted through dentin in quantities adequate to polmerize resin located several milimeters from the light source (an optical fiber). The spread of polymerization in a camphorquinone activated resin due to 488 nm light emanating from an opaque plastic canal was compared with light emanating from a canal of the same diameter in tooth dentin. Results indicated that irradiation of a resin-filled chamber via an opaque canal generated a series of ellipsoidal forms, while irradiation via a root canal generated bullet-shaped forms of much larger volume and weight. The base of these bullet-shaped forms was flat against the dentin-resin interface and surrounded the canal. These results indicated that 488 nm argon laser light was transmitted through dentin and could act to polymerize resin at a distance of several millimeters from the canal. Further experiments verified that resin in lateral canals of tooth roots was readily polymerized by 488 nm light applied at low power levels (50 mW). These experiments demonstrate the effectiveness of the argon laser in polymerizing light activated dental resins located within or adjacent to tooth dentin at distances up to several milimeters from the fiberoptic terminus. The flexibility and control that these procedures make possible in the obturation of root canals may lead to substantial improvements in endodontic therapy. PMID- 1861565 TI - Fluorescence localization of early colonic cancer in the rat by hematoporphyrin derivative. AB - Laser excitation of hematoporphyrin derivatives (HPD) localizing in tumors of the tracheobronchial tree and bladder is useful in the identification and treatment of those tumors. A comparable utility for HPD in the endoscopic localization of colonic tumors may be possible. In this study the ability of HPD to identify 1,2 dimethylhydrazine (DMH) induced colon cancer in rats is evaluated. A total of 111 rats were studied with HPD. Sixty-nine rats received weekly injections of DMH (20 mg/kg) and 42 received injections of the vehicle alone. Twenty-four hours after the intravenous injection of 5 mg/kg of HPD, 18 DMH-induced tumors were identified by visual fluorescence using excitation by either a blue light (390 436 nm) or an argon laser (488 and 514 nm). This represented 100% of the visually or microscopically detected tumors. Seventy-five fluorescent areas were noted that did not contain evidence of cancer. The majority (63) of false positive areas contained lymphoid follicles. All but 2 false positive areas (73/75, 97%, p less than .001) were seen in DMH-treated animals, suggesting that they were an artifact of DMH treatment. HPD fluorescence did not identify microscopic dysplasia. We conclude that HPD fluorescence is an effective method of identifying early colonic cancer and may have a potential clinical role in patients at high risk for colorectal cancer. PMID- 1861567 TI - Fluorescence guided excimer laser ablation of intervertebral discs in vitro. AB - Laser induced fluorescence of intervertebral discs was investigated in this study for the first time in order to develop a fluorescence guided percutaneous excimer laser discectomy. For this purpose 35 human cadaveric intervetebral discs from level L1 to L5 were irradiated with a 308 nm XeCl excimer laser with a 60 nsec pulse width at 10, 20 and 30 mj/mm2. Laser light was transmitted over a 1000 microns core optical fiber. Fluorescence emitted from the irradiated tissue was transmitted back over the same fiber over a semireflective mirror to another optical fiber, coupled into a spectrograph and O-SMA optical simultaneous multichannel spectral analyzer system. The spectral lineshape of both the annulus fibrosus and the nucleus pulposus was characterized by a broadband emission between 320 nm and 616 nm with 3 peak emissions at 358, 423 and 457 nm. Relative intensities were calculated by forming two ratios of the peak intensities of the three peaks (R1 = I 423/I 358; R2 = I 423/I 457). Statistical analysis of both ratios revealed a highly significant discrimination between annulus fibrosus and nucleus pulposus (P less than 0.001). Under penetrating conditions multiple recorded spectra showed the spectral profile of subsequently ablated nucleus and annulus. The results of this study demonstrate that discrimination between annulus fibrosus and nucleus pulposus by excimer laser-induced fluorescence is feasible under laboratory conditions. Fluorescence spectroscopy could possibly be developed into a valuable guiding system for percutaneous laser discectomy. PMID- 1861566 TI - Excimer laser ablation of fibrocartilage: an in vitro and in vivo study. AB - To date, lasers have found only limited applications in orthopedics. We employed a 308 nm XeCl excimer laser for ablation of fibrocartilage, in order to investigate the feasibility of excimer laser assisted meniscectomy. Experiments were conducted both in vitro and in vivo. For the in vitro study, human menisci, obtained during surgery and autopsy, were irradiated via a 600 microns core fiber at radiant exposures ranging between 20 mj/mm2 and 80 mj/mm2, at 20 Hz. Ablation rate measurements and histological analysis of the samples were performed. The ablation rates were found to range from 3 microns/pulse to 100 microns/pulse depending on the radiant exposure and/or the applied pressure on the fiber delivery system. Thermographic analysis was also performed during pulsed excimer as well as CW Nd:Yag and CW CO2 laser irradiation. Temperatures were lower for excimer laser (Tmax less than 65 degrees) than CW ND: Yag (Tmax less than 210 degrees) or CW CO2 (Tmax less than 202 degrees) laser. For the in vitro study, medial meniscectomy was performed in 15 rabbits with the excimer laser and a CW Nd:Yag laser in the right and left knee respectively. Excimer laser irradiation was performed at 70 mj/mm2. Nd:Yag irradiation was performed via a 600 microns core fiber at power outputs between 20 to 40 W for 10 and 20 seconds duration. The healing response to injury was investigated by histological analysis of the menisci after 1 day, 1, 2, 4, and 8 weeks following the laser procedure. Excimer laser treated menisci showed less inflammatory reaction and noticeable repair with minimal inflammatory response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861568 TI - CW laser ablation velocities as a function of absorption in an experimental one dimensional tissue model. AB - One-dimensional continuous-wave laser tissue ablation models predict that the steady-state ablation velocity is independent of the optical absorption of the tissue and proportional to laser power density. This theoretical result was tested in an experimental model that approximates the one-dimensional situation. The model consists of 3 to 4 mm-diameter polyacrylamide rods irradiated at one end with an argon laser beam with uniform power density. It was found that ablation velocity is indeed independent of the light absorption coefficient in the material and proportional to the incident power density. Analysis of the relation between the experimental velocities and the power density showed that approximately 40% of the incident laser light is reflected or attenuated in the escaping vapors. Furthermore, compared to the actual absorbed laser power, heat loss caused by thermal radiation and convection from the side surface of the rod is considerable during ablation, especially at lower power densities. This heat loss is not present in a true one-dimensional geometry and creates therefore a marked difference between the rod and one-dimensional geometry. Computations show that in the pre-ablation stage the heat losses from the rod can be neglected, compared to the absorbed energy. In this case the rod is a very good approximation of the true one-dimensional situation. PMID- 1861569 TI - Laser resistant stainless steel endotracheal tube: experimental and clinical evaluation. AB - A fire due to endotracheal tube (ET) ignition is a catastrophic event that may occur during laser surgery of the upper airway, regardless of the wavelength utilized. Although methods exist that permit laser surgery without an ET, this is frequently not feasible. The current investigation was undertaken to evaluate the efficacy of a double-cuffed stainless steel ET, first in the laboratory and subsequently in a clinical setting. Bench testing was performed using CO2 (both standard and milliwatt) and KTP/532 lasers. Only the distal polyvinyl chloride cuffed end of the tube was potentially ignitable, however, the appropriate use of saline to fill the cuffs allowed only for cuff perforation without ignition. Canine testing was performed in 10 animals: 4 dogs were intubated from 3 to 4.5 hours with the laser resistant stainless steel endotracheal tube (LRSS-ET) (Laser Flex Tracheal Tube; Mallinckrodt Anesthesia Products, St. Louis, MO) and 2 with an aluminum tape wrapped red rubber ET. Visual and histological examination were performed in both groups at 3 and 7 days. Four dogs underwent CO2 laser laryngeal surgery with visual and histological examination performed at 7 days postoperatively. No untoward effects could be demonstrated due to the LRSS-ET. A clinical study was then performed in 24 patients who underwent laser surgery of the upper aerodigestive tract with either a CO2 or KTP/532 laser. In all cases ventilation was adequate, the shaft of the LRSS-ET proved impervious to the laser, and the distal end of the tube protected the tracheobronchial tree safely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861570 TI - Energy metabolism of the liver in brain dead dogs assessed by 31P-NMR spectroscopy and arterial ketone body ratio. AB - The changes in hepatic energy state were assessed by 31P-nuclear magnetic resonance spectroscopy (31P-MRS) and arterial ketone body ratio (AKBR) in brain dead dogs. 31P-MRS and AKBR were measured before and at 3 hours after brain death. Wiggers' shock model was employed to compare the energy metabolism during hypotension. 1) The brain death model: Systemic blood pressure changed from 178.3/115.0 mmHg (mean) in the control period, to 259.5/162.5 mmHg during Cushing phenomenon (CU period) and to 63.3/51.7 mmHg after completion of brain death (BD period). beta-ATP/Pi increased from 1.27 +/- 0.14 (mean +/- SEM) to 1.46 +/- 0.16 in the early CU period, and then decreased to 1.11 +/- 0.15 at 60 minutes after BD, followed by a gradual increase to 1.33 +/- 0.13 at 3 hours after BD. Intracellular pH (pHi) increased alkaline to the control value. AKBR decreased from 1.10 +/- 0.26 to 0.46 +/- 0.15 in the CU period (p less than 0.05) and then increased to 1.48 +/- 0.25 after BD. 2) Wiggers' shock model: Systemic blood pressure was 190.0/112.5 mmHg in the control period, 83.8/51.3 mmHg during exsanguination (EX period) and 185.0/117.0 mmHg after retransfusion (RT period). beta-ATP/Pi decreased from 1.17 +/- 0.13 to 0.61 +/- 0.10 in the EX period (p less than 0.05) and increased to 1.37 +/- 0.08 in the RT period. The pHi deviated from 7.33 +/- 0.07 to 6.82 +/- 0.14 in the EX period (p less than 0.01) and to 7.51 +/- 0.21 in the RT period. AKBR decreased from 1.00 +/- 0.11 to 0.21 +/- 0.04 in the EX period and increased to 1.08 +/- 0.12 in the RT period. The energy metabolism of the liver was well maintained in the state of brain death in spite of remarkable hypotension, although that was not the case with Wiggers' shock model. It was suggested that the combination of 31P-MRS and AKBR was useful for the evaluation of graft liver viability. PMID- 1861571 TI - Characterization of the L-tryptophan transport system in the liver of growing rats. AB - In order to characterize the system of L-tryptophan (TRP) transport into liver during the growing period of 10 to 42 days, the changes of tryptophan 2,3 dioxygenase (TDO) activity, levels of serum, liver, brain, and muscle TRP, and the rate and mode of TRP uptake into isolated hepatocytes were examined in male Wistar rats. Liver TDO activity increased rapidly at 16 days of age. A marked and rapid decrease in free serum TRP level occurred before weanling, while a small decrease in total serum TRP level was found after weanling. The change of liver TRP level was similar to that of free serum TRP level and correlated well. There was a significant inverse correlation between liver TDO activity and either free serum TRP level or liver TRP level. A rapid change in TRP level did not occur in brain and muscle during the growing period. The concentrations of brain and muscle TRP correlated better with those of total serum TRP than with those of free serum TRP. The rate of TRP uptake into hepatocytes isolated from rats aged 10 days was lower than that from rats aged 21 and 42 days. The former hepatocytes were lacking in a high-affinity saturable transport component for TRP uptake which was present in the latter ones. The present results indicate that a great change in the system of TRP transport into liver occurs in growing rats, and that in suckling rats a high level of free serum TRP contributes to the efficient transport of the amino acid into the liver. PMID- 1861572 TI - Stroke in the young. (Part I). AB - We have discussed some of the more common etiologic categories found in young patients with stroke. Though many of the causes are rare, in the aggregate they account for many of the conditions leading to stroke. In Part II of this series (July 1991), we will explore some of the less common causes of stroke in the young and outline an approach to the patient. PMID- 1861573 TI - The automatic implantable cardioverter-defibrillator: update 1990. PMID- 1861574 TI - Calcitonin and the treatment of osteoporosis. AB - Calcitonin, a potent inhibitor of bone resorption, is an important agent for the treatment of osteoporosis. An analgesic effect of salmon calcitonin has also been reported. The recent development of calcitonin nasal spray should eliminate the need for injections. PMID- 1861575 TI - The efficacy of amiodarone in the treatment of refractory nonsustained ventricular tachycardia. AB - Amiodarone is very effective in suppressing refractory nonsustained ventricular tachycardia. Efficacy can be assessed after one week of therapy with continued long-term response in the vast majority of patients. PMID- 1861576 TI - Augmentation rhinoplasty utilizing cranial bone grafts. PMID- 1861577 TI - Glaucoma treatment and the laser revolution. AB - We are just beginning to see the potential uses of laser energy to treat glaucoma. Each of the lasers described here has technical problems that make them less then perfect, but it is only a matter of time before we will be able to predictably alter the internal structures of the eye to better control any type of glaucoma. PMID- 1861578 TI - The neurosurgical treatment of intracranial aneurysms in the community hospital. PMID- 1861579 TI - Mexiletine-associated left ventricular dysfunction: a case study. AB - Mexiletine is a lidocaine analogue used in the treatment of symptomatic ventricular arrhythmias. However, in selected individuals with baseline diminished left ventricular function, it may possess clinically significant negative inotropic effects. PMID- 1861580 TI - Proarrhythmia: disparity of programmed electrical stimulation results and spontaneous occurrence: a case report. PMID- 1861581 TI - Cancer immunotherapy. Part II: New approaches. PMID- 1861582 TI - July 1991. Selected communicable diseases in Maryland in 1990. PMID- 1861583 TI - Henry N. Wagner Jr. MD: winner of the American Medical Association's Scientific Achievement Award. Interview by Michelle Burke and Betsy Newman. PMID- 1861584 TI - Stroke in the young. Part II. AB - Evaluation of the young stroke patient often requires an interdisciplinary approach because of the complexity of the problems encountered. We discuss some of the less common causes of stroke and present an approach to the patient. PMID- 1861585 TI - Disseminated histoplasmosis in AIDS patients in Maryland. AB - These patients demonstrate the difficulty in arriving at the diagnosis of disseminated histoplasmosis. The diagnosis in two of the three patients also served as the initial AIDS case-defining opportunistic infection. In each of these patients, the clinical presentations were atypical and in only one patient was a positive exposure history elicited. Recurrent bowel obstruction was the presenting complaint in the first patient and the diagnosis was made only on pathologic exam of the resected small bowel. The second patient's diagnosis was made on biopsy of the colon via colonoscopy. The third patient's diagnosis also eluded an extensive FUO workup; he was diagnosed by bone marrow culture and silver stain of a mediastinal lymph node biopsy, despite serial negative serologic tests for histoplasmosis. The first two patients had significant gastrointestinal disease which is a relatively unusual manifestation for disseminated histoplasmosis. The third patient illustrates the limited diagnostic usefulness of serologic testing in AIDS patients and the continued usefulness of bone marrow analysis in an FUO evaluation. In conclusion, these case presentations demonstrate that disseminated histoplasmosis in patients with HIV infection can present with unusual manifestations, outside of the typical endemic arca, without a positive exposure history or positive serologic test, and may be the initial AIDS case-defining opportunistic infection in these patients. Consequently, a disseminated histoplasmosis should be considered in all AIDS patients with perplexing clinical presentations. PMID- 1861586 TI - Neurosonology: its place in diagnostic imaging. PMID- 1861587 TI - When is it appropriate to prescribe hearing aids for patients ... and when not? AB - There are many factors which enter into the decision about why, where, and when to prescribe hearing aids. The key questions that must be answered to make this determination are outlined here. PMID- 1861588 TI - Amos A. Evans MD: father of American naval medicine. PMID- 1861590 TI - [Distribution of radioactive aerosols in the lungs of patients with bronchial obstruction]. AB - The type of distribution of a radioaerosol in the lungs changes greatly in patients with sharp significant disorders of ventilation and with local pathology. The estimation of distribution of an inhaled aerosol together with lung ventilation capacity values permits the definition of 5 types of distribution, thus improving the diagnosis of diseases of the respiratory organs including early stages of their development, and increasing therapeutic efficacy. PMID- 1861589 TI - A clinical moment with ... diabetes. Why did my symptoms of hypoglycemia change? PMID- 1861591 TI - [A study of the evacuatory function of the small and large intestines using the dynamic scintigraphic method in inflammatory diseases of the intestines]. AB - Intestinal and colon evacuatory function was studied in 10 patients without pathology of the digestive organs and in 66 patients with chronic colitis. This method allows adequate assessment of the state of the hepatobiliary system, intestinal and colon evacuatory function without additional radiation exposure of the examinees and personnel. PMID- 1861592 TI - [X-ray fluorescent analysis of the content of stable iodine in the diagnosis of thyroid gland diseases]. AB - Radiofluorescent analysis (RFA) with the help of various devices and a new method of investigation was employed for a combined in vivo study of 1) the concentration (in micrograms/l g); and 2) the total amount (in mg) of stable iodine in the thyroid; 3) a scan of the distribution of halogen in the organ; 4) organ mass (in g) in the control groups, in 15 patients with toxic goiter before and after mercasolil therapy, and in 6 patients with endemic goiter after iodine prophylaxis. The importance of some of the indices in the diagnosis and therapy of patients with toxic goiter was shown. PMID- 1861593 TI - [Deciphering an ultrasound image using the SVIT-MIKRO digital processing complex]. PMID- 1861594 TI - [Radioimmunodiagnosis in the correction of plasmapheresis methodology in thyrotoxicosis]. AB - Differences in the rated and actual results were revealed during postoperative plasmapheresis in patients with thyrotoxicosis who did not tolerate or were resistant to thyrostatics. It was assumed that it was caused by a rise of the level of thyroid hormones resulting from heparin premedication. Gravitation plasmapheresis following heparin administration (150-200 U per 1 kg of body mass) was used in a study group of 25 patients. A dynamic study of T4, T3 and TSH was conducted with the help of radioimmunodiagnosis, based on the antigen-antibody reaction using radioimmunoassay kits. The "euthyroid" effect of plasmapheresis was shown to change as a result of heparin premedication. A significant rise of the levels of T4 and T3 by 63 and 36% was proved. The mechanism of this change was considered. The results were used for a choice of an optimum combination plasma substitutes (a mixture of albumin--30% of the total volume of substitution, and rheopolyglycine) to enhance the efficacy of preoperative preparation. PMID- 1861595 TI - [Clinico-electrocardiographic evaluation of the state of the cardiovascular system inpersonnel engaged in liquidating the consequences of the accident at the Chernobyl Atomic Power Station]. AB - The paper is concerned with analysis of the results of clinico electrocardiographic investigation of 107 rescuers, engaged in the elimination of the effects of the Chernobyl accident. A high percent (27.2%) of the detectability of borderline arterial hypertension was noted among the rescuers (aged to 39) that was determined by a strong psychoemotional tension resulting from work and radiation phobia. PMID- 1861596 TI - [The relation of the times of onset of vomiting to the magnitude and power of the dose of ionizing radiation]. AB - The paper is concerned with analysis of correlation of the time of appearance of vomit in a person and a mean dose rate of prolonged gamma-radiation in the persons affected at the Chernobyl accident. The data were approximated by power function. For irradiation with a constant dose rate (P) such correlation looks like Tp = 2.48p-0.5, where Tp is the time of the beginning of vomit, hours after the beginning of irradiation. A semiempirical model combining different conditions of irradiation was formed. Prognosis of a severity of lesion with relation to the time of vomit was given for different conditions of irradiation. PMID- 1861597 TI - [Lethal developmental defects in the offspring of a population living in a territory with traces of radioactivity]. AB - The paper is concerned with the materials of a study of long-term effects of irradiation at small doses of a limited population, taking by way of example lethal developmental defects in descendants. In 1957 a radioactive trace was formed as a result of an explosion of a tank with highly active radiochemical by products. The population in this area was exposed to irradiation. Mortality from lethal developmental defects in the descendants was analyzed. The data obtained have shown that the effect on the gonads of external irradiation at doses of 0.1 0.5 Sv (33,500 persons) revealed no statistically significant variations in the mortality of the descendants from developmental defects as compared to the controls. PMID- 1861598 TI - [Dynamics of the immunohematologic indices in patients with acute III-IV degree radiation sickness in the post-pancytopenia period]. AB - The paper is concerned with the results of determining the total number of lymphocytes, T-lymphocytes and their immunoregulatory subpopulations, B lymphocyte of peripheral blood, serum IgA, IgG and IgM in 44 patients with ARS, II-IV degree at days 37-109 after the Chernobyl accident. Bone marrow transplantation was performed in all the patients not later than on the 14th day. Among lymphocytes, T-lymphocytes were shown to restore to normal first, the T helpers/T-suppressors ratio being decreased. In 2 survivors this ratio remained decreased 2 mos. after the normalization of peripheral blood indices. Possibilities of correction of the revealed disorders with immunomodulators were discussed. PMID- 1861599 TI - [The possibility of using the method of neutron activation radiography to detect micro-quantities of environmental radioactive pollutants]. AB - A method of neutron-activation radiography was employed to investigate U distribution in leaves of plants (poplars, birches), growing in areas of mining ores with a high level of U which penetrates plants from the soil via the root system and appears on the surface of leaves, repeating their macrostructure. U also falls out on the surface of leaves in radioactive dust. The shapes of U manifestation permit the identification of its routes of penetration of the leaves of plants. Local U concentration even in an insignificant total excess of a radiation background can be considerable, leading to the destruction of tissues of plants as a result of alpha-radiation of U nuclei. A conclusion has been made of the danger of contamination of agricultural plants, growing in areas with ecological problems. PMID- 1861600 TI - [Present trends in the development of radiotherapy]. AB - New potentialities of radiotherapy of cancer patients are associated with three scientific directions: investigations in clinical radiology, the use of advantages of radiation advanced technology and guarantees of therapeutic quality. The first direction includes scientifically substantiated regimens of non-classic dose fractionation, various radiomodifiers and their combinations, and individual prognosis of a tumor response to ionizing radiation. This direction based on 3000 cases, holds promise. The second direction is associated with the advantages of modern technology used for diagnosis, topometry and radiotherapy design. The third direction is intended to reduce differences in radiotherapy quality between research institutes and cancer hospitals. PMID- 1861601 TI - [Software for processing rapid and slow digital radiographic images]. PMID- 1861602 TI - [Principles and methodology of densitometry in computed tomography]. PMID- 1861603 TI - [Morphological and biochemical indices of the blood during thermoradiotherapy of laryngeal cancer]. PMID- 1861604 TI - [Use of the Ekran-3 slide projector for self-instruction of students in a course of radiodiagnosis]. PMID- 1861605 TI - [The main trends in the pharmacological correction of radiation scleroses]. PMID- 1861606 TI - Services of UMKC's Lowry Clinic evaluated. PMID- 1861607 TI - An overview of the transmandibular implant. PMID- 1861608 TI - Fortysomething: recognizing faces at one's 25th reunion. AB - Twenty-four to 26 years after their high school graduation, subjects matched 40 photographs of former classmates taken from the high school yearbook with 40 current photographs of these same former classmates. Compared with age-matched control subjects who had no prior familiarity with the persons depicted in the photographs, the former classmates were superior at matching the old and new photographs. Generally, same-orientation photographs (i.e., old and new photographs taken from the same side) were matched more accurately than different orientation photographs. Prior familiarity, however, rendered the orientation factor unimportant. These findings are discussed in terms of the processes that underlie facial recognition over very long intervals and in terms of their psycholegal implications. PMID- 1861609 TI - Familiarity and recognition of faces in old age. AB - Elderly persons exceed young adults in false recognitions of new faces. One account claims there are age-related deficits in memory for context of encounter with faces. Because of these deficits, elderly persons frequently recognize faces on the basis of perceived familiarity (i.e., resemblance to face representations in memory), which is high for some new faces. To test this context-recollection hypothesis, we had young adult and elderly subjects judge whether faces: (1) had been seen previously in a test (though no face was repeated), and (2) were subjectively familiar (though no face was famous). The elderly exceeded the young subjects in seen-before judgements (false recognitions), and only the elderly showed a positive correlation between false recognitions and subjective familiarity. In Experiment 2, this finding was extended from false recognitions to correct recognitions, supporting the view that elderly persons, compared to young adults, rely more on resemblance in recognizing faces. PMID- 1861610 TI - Some structural determinants of melody recall. AB - Sophisticated musicians were asked to recall, using musical notation, a set of unfamiliar folk tunes that varied in rhythmic structure and referents of tonality. The results showed that memory was facilitated by tonic triad members marking phrase endings, but only when their presence was highlighted by a corresponding pattern of temporal accents. Conversely, recall significantly declined when tonal information was either absent or obscured by rhythmic structure. Error analyses further revealed that the retention of overall pitch contour and information at phrase ending points varied as a function of these manipulations. The results are discussed in terms of a framework that links the acts of perceiving and remembering to a common attentional scheme. PMID- 1861611 TI - Retrospective duration estimation of public events. AB - In three experiments, we investigated subjects' retrospective estimation of the duration of publicly reported events such as, for example, the Falkland's war. In Experiment 1, duration estimates were found to be positively correlated with event knowledge, in keeping with Ornstein's (1969) model of duration estimation. Event duration was, however, generally underestimated, suggesting that the relationship between event knowledge and estimated duration might reflect an increase in estimation accuracy. Other results of Experiment 1 were consistent with this interpretation and suggested that the duration estimates might be largely reconstructed. In Experiment 2, duration estimates of specific events and general categories of events were found to be highly correlated, and the subjects in Experiment 3 indicated that they used knowledge of the general characteristic of different types of events to estimate event duration. Overall, reallife duration estimates appear to be based on a combination of specific event information and knowledge derived about that category of event. PMID- 1861612 TI - Depth of phonological recoding in short-term memory. AB - In testing the hypothesis that surface phonetic form is included in short-term memory (STM) representation, the tone sandhi phenomenon in Mandarin Chinese was exploited, and, as a prerequisite, the hypothesis that tonal similarity affects STM of verbal material in a tone language was also tested. In Experiment 1, subjects recalled visually presented sequences of seven monosyllabic Chinese morphemes having either the same tone or different tones. More errors were made on the monotonal sequences than on the multitonal sequences, confirming the effect of tonal similarity on STM. In Experiment 2, subjects recalled visually presented sequences of disyllabic nonsense words. The sequences were designed in such a way that half of them were subject to the tone sandhi rule in Mandarin Chinese, whereas the other half were not. The consequence of applying the tone sandhi rule, as designed, was to make all the first characters in the sequences identical in pronunciation, thus creating potential phonological confusion. More errors, indeed, occurred on the sequences subject to the tone sandhi rule than on those not subject to it, indicating the existence of a surface phonetic representation in STM. The findings in this study provide further insight into the phonological mechanism of STM. Different accounts for this mechanism are also discussed in the light of the new findings. PMID- 1861613 TI - Conditional reasoning and causation. AB - An experiment was conducted to investigate the relative contributions of syntactic form and content to conditional reasoning. The content domain chosen was that of causation. Conditional statements that described causal relationships (if mean value of cause, then mean value of effect) were embedded in simple arguments whose entailments are governed by the rules of truth-functional logic (i.e., modus ponens, modus tollens, denying the antecedent, and affirming the consequent). The causal statements differed in terms of the number of alternative causes and disabling conditions that characterized the causal relationship. (A disabling condition is an event that prevents an effect from occurring even though a relevant cause is present). Subjects were required to judge whether or not each argument's conclusion could be accepted. Judgements were found to vary systematically with the number of alternative causes and disabling conditions. Conclusions of arguments based on conditionals with few alternative causes or disabling conditions were found to be more acceptable than conclusions based on those with many. PMID- 1861614 TI - Determinants of spatial priming in environmental memory. AB - Spatial priming in recognizing objects in experimentally learned environments has been proposed as strong evidence for spatial organization of environmental memory. However, in all studies showing recognition priming effects, encoding and rehearsal contiguity may have coincided with spatial proximity, and thus priming may have been due to temporal associations formed during rehearsal, not encoded spatial relations per se. We investigated this question in four experiments, using a trip trial learning method in which temporal contiguity and spatial relations were independent. In Experiment 1, no spatial priming in recognition was found, even though indirect evidence suggested that subjects had encoded spatial relations. In Experiment 2, the trip trial method was compared with the free study procedure commonly used in previous priming studies. Spatial priming occurred only for free study subjects, even though the two groups were equivalent on direct measures of encoding accuracy. In Experiment 3, spatial priming in recognition was obtained with a modification of the trip trial method in which temporal and spatial contiguity were deliberately confounded. In Experiment 4, the unmodified trip trial method produced spatial priming in a location-decision task. Taken together, our results suggest that environmental memory may be spatially organized, but retrieval of object identities does not necessarily activate encoded spatial relations. PMID- 1861615 TI - Perceptual fluency and affect without recognition. AB - A dichotic listening task was used to investigate the affect-without-recognition phenomenon. Subjects performed a distractor task by responding to the information presented in one ear while ignoring the target information presented in the other ear. The subjects' recognition of and affect toward the target information as well as toward foils was measured. The results offer evidence for the affect without-recognition phenomenon. Furthermore, the data suggest that the subjects' affect toward the stimuli depended primarily on the extent to which the stimuli were perceived as familiar (i.e., subjective familiarity), and this perception was influenced by the ear in which the distractor or the target information was presented. These data are interpreted in terms of current models of recognition memory and hemispheric lateralization. PMID- 1861616 TI - Availability and category-frequency estimation. AB - Individuals judged how often examples of taxonomic categories had occurred in a study list. An availability hypothesis was tested--that frequency estimates are based on the retrieval of instances. Cued (by category names) recall of the examples served as an index of availability. The hypothesis was confirmed--there were strong positive correlations between frequency judgments and recall (with the influence of actual frequency removed)--given one or more of the following conditions: List instances were not categorized aloud as they were presented; frequency estimation was preceded by cued recall; frequency estimation was delayed by a week. Limitations on availability occurred under other conditions- notably, when individuals, during list presentation, named the categories to which items belonged and received feedback about their categorizations. Under these circumstances, correlations of frequency estimation and recall were often not significantly different from zero, and frequency judgments and recall sometimes reacted differently to changes in independent variables (e.g., frequency judgments of young and elderly subjects did not differ reliably, even though cued recall of young persons markedly exceeded that of elderly subjects). PMID- 1861617 TI - The Ranschburg effect: the role of guessing strategies. AB - The Ranschburg effect refers to the finding of impaired serial recall of items repeated on a list. One account attributes this effect to the use of a strategy where subjects avoid using as guesses stimuli that they had recalled elsewhere on the list. Support for this interpretation is reported here. The Ranschburg effect is eliminated when subjects are instructed to avoid guessing. Also, the Ranschburg effect is found in partial report only when subjects are told that the crucial item occurred elsewhere on the list. PMID- 1861618 TI - Staffing of mental health organizations, United States, 1986. AB - Between 1984 and 1986, the number of full-time equivalent (FTE) staff employed in specialty mental health organizations in the United States increased 12 percent from 440,925 to 494,591. Much of this increase could probably be attributed to the increase in the number of mental health organizations during this period from 4,438 to 4,747. With the exception of freestanding psychiatric outpatient clinics, which showed a 1 percent decrease, all of the other mental health organization types showed varying amounts of increase in FTE staff, with the most notable gains reported by private psychiatric hospitals, RTCs for emotionally disturbed children, and multiservice mental health organizations. Of the 494,591 FTE staff employed in mental health organizations in 1986, 70 percent were classified as patient care staff and 30 percent as administrative and support staff. Private psychiatric hospitals, State mental hospitals, and freestanding psychiatric outpatient clinics had slightly higher percentages of administrative and support staff (40, 35, and 33 percent, respectively), with consequent smaller percentages of patient care staff (60, 65, and 67 percent, respectively). For all other organization types, the percentages of patient care staff were higher, varying from 70 to 87 percent. Professional patient care staff constituted 47 percent of all FTE staff in mental health organizations in 1986, and other mental health workers (less than B.A.) represented only 23 percent of the total. Among each of the organization types, however, the percentages of professional patient care staff were generally higher, and the percentages of other mental health workers lower, with the major exception of State mental hospitals. Seventy-five percent or more of the staff employed in the various types of specialty mental health organizations in 1986 worked on a full-time basis, with the exception of freestanding psychiatric outpatient clinics and the separate psychiatric services of non-Federal general hospitals in which full-time staff represented only 53 and 67 percent of all staff, respectively. For the most part, a majority (50 percent or more) of each of the staff disciplines employed in specialty mental health organizations worked on a full-time basis. The major exceptions were psychiatrists and other physicians, most of whom worked either on a part-time or a trainee basis. PMID- 1861619 TI - Employment retention and career movement among individuals with mental retardation working in supported employment. AB - Results of a 24-month analysis of employment retention and replacement needs of a sample of 302 individuals placed into supported employment were reported. Supported employees experienced regular movement in and out of the labor market. Approximately 30% of them were still employed in their original employment situation 24 months following initial placement. An additional 20% were employed in subsequent employment situations, and over 31% had lost their employment and were returned to a referral pool to await replacement. Implications for future supported employment service delivery and funding were discussed. PMID- 1861620 TI - Choices. PMID- 1861621 TI - Programs and services received by older persons with mental retardation. AB - Findings from a study of the programs and services received by a national sample of older persons with mental retardation were reviewed. Individuals were selected from a national sample of all facilities owned, operated, or licensed by developmental disabilities agencies having one or more persons 63 years of age or older with mental retardation. Facilities included foster care, small group homes, large private facilities, and state-operated facilities. One or two residents per facility were studied. A total of 370 individuals in 235 facilities were surveyed (10% of all eligible facilities). Comprehensive information on resident characteristics, day program participation, and services received was gathered through extensive questionnaire and telephone interviews of primary careproviders and directors of the day programs attended by individuals in the resident sample. Differences in programs and services received were presented by facility type. PMID- 1861622 TI - Do attitudes towards persons with handicaps really shift over time? Comparison between 1975 and 1988. AB - A replication of a study by Spreen (1977) was conducted to assess whether a positive shift in attitudes towards persons with mental retardation has occurred. Undergraduate students (N = 191) were tested. Results compared to those of Spreen (1977) showed a positive shift over the 13-year period. We also tested the hypothesis that exposure to a course on developmental disabilities and contact with individuals with mental retardation would improve students' attitudes. Findings support this hypothesis, although results suggest the influence of a third variable, namely, public awareness. PMID- 1861624 TI - Parent involvement in transition programs. AB - Parent involvement in programs facilitating the transition of persons with handicaps from school to adult life (work, independent living) was examined. The survey found that a significant number of parents were unaware of any transition program for their offspring, although virtually all parents desired involvement of some kind. Parents also indicated preferences relating to their child not living at home upon graduation from school, working in the community, and earning a wage greater than or equal to the minimum. PMID- 1861623 TI - Developmentally based personality assessment of adults with mental retardation. AB - Difficulties in assessing emotional and personality disturbances in adults with mental retardation were discussed and an evaluation method overcoming some of these problems presented. Overshadowing, inappropriate equation of emotional symptoms with cognitive limitations, and failure to adjust for the differing functioning levels among persons with mental retardation when judging pathology were cited as reasons to include a specific developmental factor in assessing this group. Projective tests were cited in the literature as being effective techniques, and an apperceptive technique originally intended for use with children was presented as a means of adding the needed developmental factor. PMID- 1861625 TI - Evidence that potassium deficiency induces growth retardation through reduced circulating levels of growth hormone and insulin-like growth factor I. AB - Growth retardation and impaired protein synthesis are major characteristics of potassium (K)-deficiency in animals and man. We have evaluated the effect of K deficiency on growth, serum growth hormone (s-GH), insulin-like growth factor I (s-IGF-I), and insulin (s-insulin) in young rats. After 10 days on K-deficient fodder, 4 1/2-week-old rats showed a 54% reduction in serum potassium (s-K) and a weight gain that was reduced by 97%, compared with pair-fed controls. In addition, tail length, tibia length, and muscle weight of soleus in K-depleted animals were all significantly reduced compared with pair-fed controls. The growth retardation was accompanied by a 46% reduction in s-IGF-I, while s-insulin showed no decrease. K-repletion in animals depleted for 7 days showed complete normalization of s-K within 24 hours, in addition to a significant increase in both s-IGF-I and weight. In 4-week-old rats maintained on K-deficient fodder with variable K-content (1 to 260 mmol/kg) for 1 week, a strong correlation between the K-content of fodder and s-IGF-I could be established (r = .88, P less than .001), as well as between s-IGF-I and weight gain (r = .90, P less than .001). Furthermore, a stepwise reduction in basal s-GH was seen with the graded reduction of dietary K-content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861626 TI - Apolipoprotein E allele frequencies in non-insulin-dependent diabetes mellitus with hypertriglyceridemia (type IIb, III, IV, and V hyperlipoproteinemia). AB - We examined apolipoprotein E (apo E) allele frequencies in non-insulin-dependent diabetes mellitus (NIDDM) patients with normolipidemia or various types of hypertriglyceridemia to elucidate the association of the apo E alleles with hypertriglyceridemia in NIDDM. NIDDM patients with normolipidemia (N = 134) or hypertriglyceridemia [type IIb hyperlipoproteinemia (HLP) (N = 42), III HLP (N = 7), IV HLP (N = 96), and V HLP (N = 8)] were randomly selected from our Diabetic Clinics. Apo E phenotypes (genotypes) were determined by our rapid flat-gel isoelectric focusing method. The frequency of the epsilon 4 allele was significantly higher in the type IIb (20.2%, P less than .01) and V (25.0%, P less than .05) HLP patients than in the normolipidemic patients (8.9%), whereas the frequency of the epsilon 3 allele was significantly (P less than .025) lower in the type IIb HLP patients (78.6%) than in the normolipidemic patients (89.2%). The frequency of the epsilon 2 allele was significantly higher in the type III (64.3%, P less than .001) and IV (5.2%, P less than .05) HLP patients than in the normolipidemic patients (1.9%), whereas the frequency of the epsilon 3 allele was significantly lower in the type III (28.6%, P less than .001) and IV (82.8%, P less than .05) HLP patients than in the normolipidemic patients. Thus, it has proven that the epsilon 2 allele is related to type III and IV HLP in NIDDM, whereas the epsilon 4 allele is related to type IIb and V HLP in NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861627 TI - Fasting serum insulin in relation to fat distribution, serum lipid profile, and blood pressure in European women: the European Fat Distribution Study. AB - Samples of 38-year-old women were randomly selected from five European centers: Ede (The Netherlands), Warsaw (Poland), Gothenburg (Sweden), Verona (northern Italy), and Afragola (Naples-southern Italy). In total, 452 healthy women were studied. Anthropometric measurements were taken by one operator in each country after common training of all operators and blood parameters of all women were determined in one laboratory. Body mass index (BMI) was different among centers, mainly due to the higher values in southern Italy. Women from southern Europe had more central fat distribution than women from north European centers. Fasting serum insulin was higher in women from Poland and The Netherlands than in the other three centers. After adjustment for BMI, fasting insulin was significantly related to subscapular skinfold, subscapular to triceps skinfold ratio, waist circumference, and waist to thigh circumference ratio, although the partial correlations varied somewhat between the centers. In the pooled data, waist circumference showed the highest correlations with fasting serum insulin when adjusted for BMI. Fasting serum insulin showed significant partial correlations, adjusted for BMI, with lipid profile and blood pressure only in women from the two Italian centers. In the pooled data, fasting serum insulin was significantly positively correlated with serum triglycerides and total cholesterol and negatively to high-density lipoprotein (HDL) cholesterol and HDL/total cholesterol, independently of BMI and waist circumference. While blood pressure was not related to insulin in the pooled women, when adjusted for BMI and waist circumference; here as well, there were some differences in relationships between the centers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861628 TI - Glucose intolerance in first-degree relatives of patients with Friedreich's ataxia is associated with insulin resistance: evidence for a closely linked inherited trait. AB - Multiple and different genetic defects may be associated with the development of diabetes mellitus. Friedreich's ataxia (FA) is an autosomal recessively inherited neurologic disease associated with a high prevalence of diabetes. We previously demonstrated that patients with FA have insulin resistance prior to the development of overt diabetes mellitus. To determine if insulin resistance is an inherited characteristic in this group, we performed oral glucose tolerance tests (OGTT) on first-degree relatives, 21 parents and 17 siblings, of patients with FA. While fasting concentrations were normal, both glucose and insulin concentrations in response to oral glucose were significantly elevated compared with controls. Corrected insulin responses, CIR = I x 100/G (G-70) (I = insulin, G = glucose), were not different from controls, whereas peripheral insulin activities, A = 10(4)/Ip Gp (p = values of I and G at peak glucose concentration), were significantly decreased (FA, 0.66 +/- 0.11, P less than .001; parents, 0.63 +/- 0.06, P less than .001; siblings, 0.72 +/- 0.09, P less than .01; v controls, 1.52 +/- 0.19), indicating the presence of insulin resistance in patients and first-degree relatives. Multiple discriminant analysis was used to separate patients with FA from controls. The combination of GLUT (sum of glucose values 0 to 3 hours of the OGTT) and CIR achieved significant separation (P less than .0004). Subsequent assignment of the relatives showed that 17 of 18 parents and 11 of 16 siblings (69%) fell in the range of FA, rather than with controls. These data suggest that insulin resistance is an inherited trait in this group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861629 TI - Enhanced in vitro oxidation of plasma lipoproteins derived from hypercholesterolemic patients. AB - In vitro oxidation of plasma lipoproteins, derived from either normolipidemic or hypercholesterolemic subjects, was performed in the presence of copper ions. Following this procedure, hypercholesterolemic low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) demonstrated greater propensity for oxidation than the corresponding normocholesterolemic lipoproteins. The oxidation was determined by the concentration of thiobarbituric acid-reactive substances (TBARS), which was 44%, 71%, and 54% greater in the patients' VLDL, LDL, and HDL in comparison to the normocholesterolemic lipoproteins, respectively. An associated reduction in trinitrobenzensulfonic acid (TNBS) reactivity in the patients' lipoproteins was noted. These changes were consistent whether expressed per lipoprotein protein or per concentration. Macrophage cholesterol esterification induced by oxidized LDL was substantially increased (up to 59%) when patients' lipoproteins were used, in comparison to control lipoproteins. A positive correlation was present between the LDL cholesterol to protein ratio, the extent of lipoprotein oxidation, and macrophage uptake of the oxidized lipoproteins. The lipoprotein content of pro oxidant and antioxidant constituents was also analyzed. No measurable ferric or copper ions could be found in association with any of the lipoproteins. However, arachidonic acid content of the patients' LDL was 10.1% +/- 1.0% in comparison to 6.2% +/- 0.8% of total lipoprotein fatty acids in the control group (n = 5). Antioxidants such as vitamin E and carotenoids were significantly reduced in all patients' lipoproteins compared with those of controls. Thus, we suggest that increased cholesterol and arachidonic acid content and reduced concentration of antioxidants in lipoproteins of hypercholesterolemic patients may be responsible for the enhanced propensity for oxidation observed in these lipoproteins. PMID- 1861630 TI - Growth hormone alters lipolysis and hormone-sensitive lipase activity in 3T3 F442A adipocytes. AB - While growth hormone (GH) has long been known as a lipolytic hormone, it has been difficult to study the cellular mechanisms for this effect. Since cultured 3T3 F442A adipocytes have recently proven to be useful to study chronic effects of GH on adipocyte metabolism, we examined the effects of GH on lipolysis. In these cells, GH alone produced a dose-dependent increase in the release of glycerol after 24 to 48 hours. The maximum increase occurred with 10 ng/mL human GH. The effect of GH was similar in the presence and absence of dexamethasone. Under each condition, the stimulation of glycerol release was accompanied by a GH-induced increase in the activity of hormone-sensitive lipase (HSL), a key lipolytic enzyme. The increase in HSL required 24 hours with GH and lasted at least 48 hours. The increase in HSL activity by epinephrine, like glycerol release, was potentiated by GH. Although GH potently simulates the activity of the lipogenic enzyme glycerol phosphate dehydrogenase (GPD) in differentiating 3T3-F442A preadipocytes, GH had a negligible effect on GPD activity in the differentiated adipocytes with chronic or short-term incubation. However, in contrast to the chronic effect of GH, short-term (30-minute) incubation with GH inhibited epinephrine-stimulated glycerol release, a characteristic transient antilipolytic effect of GH. These studies indicate that chronic GH treatment is lipolytic in cultured 3T3-F442A adipocytes, and document that lipolytic responses to GH involve an increase in the activity of HSL. PMID- 1861631 TI - Impaired translocation of protein kinase C activity in human non-insulin dependent diabetes mellitus. AB - Calcium- and phospholipid-dependent protein kinase (protein kinase C; PKC) may be an important mediator in transduction of some of the cellular actions of insulin. We studied PKC activity in freshly isolated circulating mononuclear cells obtained from healthy subjects and patients with non-insulin-dependent (type II) diabetes mellitus (NIDDM). The kinase activity was measured using a specific nonapeptide substrate, Ala-Ala-Ala-Ser-Phe-Lys-Ala-Lys-Lys-amide. There was negligible calcium- and phospholipid-independent kinase activity in cytosolic and particulate fractions of cells from both control and diabetic subjects. Total (cytosolic and particulate) PKC activity of mononuclear cells from poorly controlled diabetic patients was significantly reduced compared with controls; this reduction was mainly due to a decrease in the cytosolic kinase activity. Tumor-promoting phorbol ester (TPA, 0.1 mumol/L) induced translocation of PKC activity in control cells; in contrast, this subcellular redistribution was not observed in cells from a majority of poorly controlled diabetic subjects. Increased calcium influx into the cells caused by the calcium ionophore A23187 triggered translocation of PKC activity in control cells, while it was ineffective in cells from poorly controlled diabetic patients. Cells from well controlled diabetic patients demonstrated TPA-induced translocation of the PKC activity approaching that of control cells. The total PKC activity in cells from patients with good glycemic control was normal. Impaired activation of PKC is thus associated with the insulin resistance found in patients with poorly controlled NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861632 TI - The response of parathyroid hormone to specific changes in either ionized calcium, ionized magnesium, or protein-bound calcium in humans. AB - Because the effects of specific changes in magnesium or protein-bound calcium on biologic processes in humans have not been clearly defined, we developed an experimental system to specifically lower either ionized calcium, protein-bound calcium, or ionized magnesium. As an indicator of the biological effect of these changes, we measured parathyroid hormone (PTH) in blood. To selectively dilute only one constituent, we infused one of four specially prepared solutions into each of six healthy blood donors following ordinary blood donation. Each donor received at random 450 mL of a different solution at four different blood donations. The respective concentrations of ionized calcium (mmol/L), total magnesium (mmol/L), and albumin (g/L) in these fluids were as follows: control fluid, 1.25, 1.20, 40; no calcium fluid, 0, 1.20, 40; no magnesium fluid, 1.25, 0, 40; no albumin fluid, 1.25, 1.00, 0. Using selective in vivo dilution of the volunteers' blood, we specifically lowered either (1) ionized calcium by 0.07 mmol/L (5.5%), (2) protein-bound calcium by 0.09 mmol/L (10%), or (3) ultrafiltrable magnesium by 0.03 mmol/L (4.8%). While measurements of intact PTH showed that concentrations of PTH in blood did not respond to either decreased ultrafiltrable magnesium or decreased protein-bound calcium, these measurements showed that PTH increased by 400% within 10 minutes in response to decreased ionized calcium. PMID- 1861633 TI - Effect of intensity of exercise on excess postexercise O2 consumption. AB - After exercise, there is an increase in O2 consumption termed the excess postexercise O2 consumption (EPOC). In this study, we have examined the effect of exercise intensity on the time course and magnitude of EPOC. Six healthy male subjects exercised on separate days for 80 minutes at 29%, 50%, and 75% of maximal O2 uptake (VO2max) on a cycle ergometer. O2 uptake, R value, and rectal temperature were measured while the subjects rested in bed for 14 hours postexercise, and the results were compared with those of an identical control experiment without exercise. An increase in O2 uptake lasting for 0.3 +/- 0.1 hour (29% exercise), 3.3 +/- 0.7 hour (50%) and 10.5 +/- 1.6 hour (75%) was observed. EPOC was 1.3 +/- 0.46 I(29%), 5.7 +/- 1.7 I (50%), and 30.1 +/- 6.4 I (75%). There was an exponential relationship between exercise intensity and total EPOC, both during the first 2 hours and the next 5 hours of recovery. Hence, prolonged exercise at intensities above 40% to 50% of VO2max is required in order to trigger the metabolic processes that are responsible for the prolonged EPOC component extending beyond 2 hours postexercise. PMID- 1861634 TI - Effects of clenbuterol on skeletal muscle mass, body composition, and recovery from surgical stress in senescent rats. AB - Aging decreases skeletal muscle mass and strength, which may be exacerbated by age-related diseases. There is a need for therapeutic agents to prevent or restore loss of skeletal muscle in elderly subjects with muscle wasting disorders. Clenbuterol, a beta 2-adrenergic agonist, dramatically increases skeletal muscle mass in young animals and partially prevents or restores muscle loss in experimental models of muscle wasting. However, the protein anabolic and fat catabolic effects of clenbuterol have not been studied in senescent animals. To determine whether this drug has potential for preventing or repairing muscle loss in elderly subjects, we have examined its effects in young and old rats. Clenbuterol was administered by implanted osmotic minipumps to Fischer-344 rats ages 3, 12, and 23 months, at a dose of 1.5 mg/kg/24 h for 3 weeks. The weights of five hindlimb muscles and carcass protein and fat content were determined. Clenbuterol treatment increased the weight of skeletal muscles 22% to 39% in 3 month-old rats, 19% to 35% in 12-month-old rats, and 22% to 25% in 23-month-old animals. Likewise, clenbuterol increased carcass protein content 19% in 3-month old rats, 16% in 12-month-old rats, and 24% in 23-month-old animals. Conversely, the drug reduced carcass fat content 36% in 3-month-old rats, 32% in 12-month-old rats, and 38% in 23-month-old rats. Therefore, clenbuterol had similar anabolic and catabolic effects in all age groups. In addition, clenbuterol stimulated recovery of skeletal muscle protein lost following pump implantation in senescent rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861635 TI - Insulin resistance in multiple aspects of intermediary metabolism in myotonic dystrophy. AB - The responses of circulating intermediary metabolites to a low-dose incremental insulin infusion (basal, 0.005, 0.01, and 0.05 U.kg-1.h-1) were examined in eight ambulant subjects with the multisystem disorder, myotonic dystrophy. Eight healthy subjects matched for age, gender, and body mass index served as controls. Oral glucose tolerance (75 g) was normal in all subjects. Basal (postabsorptive) hyperinsulinemia was observed in the subjects with myotonic dystrophy (8.4 +/- 2.0 v 2.3 +/- 0.2 mU/L, P less than .01) with increased basal C-peptide levels. Basal blood glycerol (0.09 +/- 0.02 v 0.05 +/- 0.01 mmol/L, P less than .05), lactate (1.14 +/- 0.12 v 0.77 +/- 0.07 mmol/L, P less than .02), and pyruvate (0.08 +/- 0.01 v 0.05 +/- 0.01 mmol/L, P less than .02) were also elevated in these subjects. During the incremental insulin infusion, circulating insulin (F = 8.2, P less than .02) and C-peptide (F = 5.1, P less than .05) levels were significantly higher in the myotonic subjects. Despite the hyperinsulinemia, circulating concentrations of lactate (F = 9.8, P less than .01), pyruvate (7.8, P less than .02), and glycerol (F = 7.5, P less than .02) were also higher in the subjects with myotonic dystrophy, providing prima facie evidence of insulin resistance in the regulation of these metabolites. During the highest insulin rate, isotopically determined metabolic clearance rate of glucose was significantly lower in the myotonic subjects (3.6 +/- 0.4 v 5.5 +/- 0.7 mL.kg 1.min-1, P less than .05), indicating impaired peripheral glucose metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861636 TI - Effect of insulin on the properties of liver carnitine palmitoyltransferase in the starved rat: assessment by the euglycemic hyperinsulinemic clamp. AB - The effect of insulin on the properties of liver carnitine palmitoyltransferase I (CPT I) was assessed in conscious starved rats with the euglycemic hyperinsulinemic clamp. A 24-hour clamp was necessary to fully reverse the effect of starvation on liver malonyl-CoA concentration, CPT I maximal activity, and apparent km and Ki for malonyl-CoA. Since glucagon was not decreased during the clamp, insulin is the major factor involved in the regulation of CPT I. PMID- 1861637 TI - Quantitation of glycogen/glucose-1-P cycling in liver. AB - A method is introduced for quantitating cycling between hepatic glycogen and glucose-1-P in humans. It depends on the administration of trace [2-3H,6 14C]galactose, a glucose load, and acetaminophen. The ratio of 3H to 14C in the glucuronide of the acetaminophen excreted in urine to that in the administered galactose provides the measure of the fraction of glycogen synthesized that is synthesized from glucose-1-P formed from glycogen. The quantity of glucose-1-P formed from glycogen that is not reconverted to glycogen is not measured. It is assumed that the glucuronide samples the UDP-glucose pool in liver from which glycogen is formed, the last glucosyl units formed from UDP-glucose in glycogen synthesis are the first broken down, and the equilibration of [2-3H]glucose-1-P with fructose-6-P is rapid relative to its conversion to UDP-glucose. During a 5 hour period, while three normal subjects and three non-insulin-dependent diabetics, who had fasted overnight, were infused with 4 mg/kg/min of glucose, the rate of glycogen breakdown, as measured using the method, was only a small percentage of the rate of glycogen synthesis. PMID- 1861638 TI - Oral discomfort and hormone replacement therapy in the post-menopause. AB - We evaluated the incidence of oral discomfort in post-menopausal women and the efficacy of hormone replacement therapy in patients complaining of such symptoms. Two studies were performed. In the first, we compared oral discomfort and oral mucosa smears in 47 patients receiving replacement therapy and in 40 untreated post-menopausal women. In the second, the efficacy of hormone replacement therapy with oestriol vaginal cream (22 patients) or conjugated oestrogens plus norethisterone acetate (10 patients) was evaluated. In the first study, oral exfoliative cytology showed a similar maturation index and volume in both groups. In the second, hormone replacement therapy improved subjective and objective symptoms in 12 out of 22 patients treated with oestriol and in 7 out of 10 patients treated with conjugated oestrogens plus norethisterone. These data suggest that oestrogen deficiency can be considered a possible cause of oral discomfort in some post-menopausal patients and that oestrogen replacement therapy may improve subjective symptoms. PMID- 1861639 TI - Compliance with hormonal replacement therapy. AB - One hundred post-menopausal women given HRT were reviewed 12 months after their first visit to determine their compliance with treatment. Sixty-one percent continued to take the therapy while 27% ceased. Most often the reason for ceasing HRT was return of bleeding but a number of women expressed fear of developing cancer or other long term complications. PMID- 1861640 TI - Changes in 40 serum proteins of post-menopausal women. AB - Sera were sampled from 83 people (pre- and post-menopausal women and men). Climacteric symptoms of 23 women were treated with conjugated estrogen. Sera were sampled serially until the 21st day of estrogen administration. Serum concentrations of 40 protein components were measured by micro single radial immunodiffusion. The serum proteins were classified into 5 types according to changes after menopause and estrogen therapy, respectively. Type 1 (decreased after menopause and increased by estrogen; alpha 1-antitrypsin, alpha 2-HS - glycoprotein, beta 2-glycoprotein III, Gc-globulin, alpha 1-lipoprotein and alpha 2-AP-glycoprotein), type 2 (unchanged and increased; ceruloplasmin), type 3 (increased and decreased; alpha 1-acid glycoprotein, haptoglobin, serum amyloid P component, Zn-alpha 2-glycoprotein, beta-lipoprotein and C1-components), type 4 (unchanged and decreased; hemopexin, antithrombin III, beta 2-glycoprotein I, prealbumin and retinol-binding-protein), type 5 (unchanged by estrogen; immunoglobulin M (IgM), IgG and others). Estrogen replacement therapy restored pre-menopausal levels of serum proteins, types 1 and 3. However, estrogen therapy was associated with significantly abnormal levels of proteins, types 2 and 4 in post-menopausal women. Serum levels of type 1 proteins and some type 5 proteins (IgM, alpha 1B-glycoprotein, C9-component and alpha 2-macroglobulin) were higher in pre-menopausal women than in men, whereas type 3 proteins were the opposite. PMID- 1861641 TI - Effect of continuous oestradiol-medroxyprogesterone administration on plasma lipids and lipoproteins. AB - Plasma lipids and lipoproteins were measured in 21 post-menopausal women after 4 and 8 months of continuous treatment with an orally administered combination of oestradiol and medroxyprogesterone acetate. The mean concentrations of cholesterol and low-density-lipoprotein (LDL) cholesterol were reduced by 12% (P less than 0.001) and 11% (P less than 0.01), respectively, after 4 months of treatment and by 9% (P less than 0.05) and 12% (P less than 0.05) after 8 months. The mean level of high-density-lipoprotein (HDL) cholesterol showed an initial fall of 5% (P less than 0.05) after 4 months and then increased by 13% (P less than 0.05) after 8 months of treatment. The plasma triglycerides level oscillated around the baseline value, but the changes were not statistically significant. Indexes such as the HDL-cholesterol/LDL-cholesterol and cholesterol/HDL cholesterol ratios, which are considered to be good indicators of atherogenic risk, showed changes towards patterns considered to be beneficial. Although the clinical significance of these changes remains uncertain at present, it seems clear that an oestradiol and medroxyprogesterone combination administered continuously produces biochemical changes which are regarded as protective against cardiovascular disease. Additionally, the endometrial inertness attributed to the continuous oestrogen-progestogen therapy would warrant its use as a good alternative in post-menopausal replacement therapy. PMID- 1861642 TI - Sexuality in sexagenarian women. AB - Sexual behavior was examined in 59 healthy, post-menopausal women between 60 and 70 years of age. Subjects were interviewed by a psychologist, completed medical and sexual questionnaires and had a gynecologic exam and blood drawn for determination of estradiol, luteinizing hormone and total and free testosterone. Partners filled out a mail-back sexual questionnaire. Thirty-nine (66%) of the group were coitally active and twenty (34%) were abstinent. The coitally active group reported higher levels of sexual desire (P less than 0.03), greater sexual satisfaction (P less than 0.007), more comfort in expressing sexual preferences (P less than 0.009) and greater pre-menopausal sexual satisfaction (P less than 0.01) and on pelvic examination were noted to have less genital atrophy (P less than 0.0005) than the abstinent group. For the entire sample sexual complaints such as decreased desire and vaginal lubrication in the female and erectile difficulties in the male were reported frequently. Of the hormones studied, higher serum levels of free testosterone were associated with reports of increased sexual desire. PMID- 1861644 TI - Psychiatric and substance abuse peer review has yet to find acceptance among Michigan physicians. PMID- 1861643 TI - A longitudinal analysis of women's attitudes toward the menopause: results from the Massachusetts Women's Health Study. AB - This paper examines women's attitudes towards menopause in a large representative sample of middle-aged women. Data were derived from the Massachusetts Women's Health Study (MWHS) which is a prospective study of 2565 women aged 45-55, randomly sampled throughout Massachusetts. The paper addressed the following questions: (1) What are women's attitudes towards the menopause and how do attitudes change as a function of menopause? (2) What variables are related to attitudes towards menopause? and (3) Do attitudes towards menopause predict subsequent symptom reporting during menopause? Results showed that the majority of women reported relief or neutral feelings about the cessation of menses and that feelings became more positive as women experienced menopause. Negative attitudes towards menopause were related to general symptom reporting and depression. Additionally, negative attitudes prior to menopause were related to subsequent symptom reporting during menopause. These results suggest that the so called menopause syndrome may be more related to personal characteristics than to menopause per se. PMID- 1861645 TI - Helping the elderly meet non-medical needs. Physicians should take an active role. PMID- 1861646 TI - The quality of midwifery care. PMID- 1861647 TI - The first International Day of the Midwife: safe birth for all. A service of celebration. Westminster Abbey May 7, 1991. PMID- 1861648 TI - International Day of the Midwife: a first for midwives in Ethiopia! PMID- 1861650 TI - Childsafe Wessex. PMID- 1861649 TI - Why do we have to wait so long? PMID- 1861651 TI - Safe delivery home. PMID- 1861652 TI - [The DNA nucleotide composition of bacteria oxidizing diethylene glycols]. AB - Nucleotide composition of DNA has been analyzed in bacteria composing the diethylene glycol-oxidizing association. It is shown that the microorganisms under study are representatives of genera Alkaligenes and Achromobacter. PMID- 1861653 TI - [The thermodynamic parameters of the conformational transitions in Mycoplasma DNA]. AB - DNA preparations have been isolated from 10 strains of phytopathogenic mycoplasms and collection culture Achole plasma laidlawii PG-8. Thermodynamic parameters of denaturation changes in the secondary structure (transconformation) of DNA of these mycoplasms have been determined. It is shown that denaturation temperature is 82.3-83.1 degree C and enthalpy of conformational DNA transitions calculated per 1 g of dry substance is 56.2-61.9 J/g. Changes in the enthalpy (delta H) and entropy (delta S) calculated per 1 mol of nucleotide pairs varied in the range of 35.6-39.0 J/m.p. and 995-109.6 J degree m.p. respectively. No linear dependence of transconformational thermal adsorption on the temperature of DNA denaturation of the studied strains of mycoplasms are revealed, which is probably connected with structural peculiarities of DNA of these microorganisms. PMID- 1861654 TI - [The microflora in suppurative-catarrhal endometritis in cattle]. AB - Microflora isolated from cattle with acute postnatal pus-catarrhal endometritis has been studied. It is shown that the given pathology is caused by associations of different bacterial species. 284 strains isolated from the uterus content of 63 sick animals have been identified, their properties being studied. Pathogenic gram-negative bacilli and gram-positive pus-producing cocci are responsible for the studied pathology. Considerable inoculation capacity has been established for conditionally pathogenic microorganisms of different species and genera whose role in pathogenesis is to be found out. PMID- 1861655 TI - [Induced bacterial chemiluminescence]. AB - Oxygen-peroxide-induced superweak luminescence of some microorganisms has been studied by means of the native chemiluminometer KhLM1Ts-01. It is established that total chemiluminescence decrease in the bacteria as follows: Escherichia coli----Bacillus subtilis----Proteus vulgaris----Bacillus mycoides----B. licheniformis----Pseudomonas aeruginosa----Staphylococcus epidermidis----S. aureus----Serratia marcescens----Salmonella enteritidis. A hypothesis is put forward on a possible mechanisms of appearance of the superweak luminescence of bacteria and expediency to use chemoluminometry to differentiate microorganisms. PMID- 1861656 TI - [The immunomorphological characteristics of a focal staphylococcal infection against a background of long-term exposure to low doses of simazine]. AB - State of immunologic and nonspecific resistance of the organism, ultra- and histostructure of the thymus, histopathology of the wall of experimental staph abscess reproduced in animals given low doses of the herbicide simazine for a long time have been studied. It is established that simazine induced the immunodeficiency state underlain by pathologic changes in the thymus. Against this background experimental abscesses developed more rapidly, alterative and exudative processes in their wall proceeding more intensively and proliferative ones--attenuating. This provides prolongation of the abscesses healing phase for an indefinite time and chronization of the process. PMID- 1861657 TI - [The characteristics of glucose consumption by an L-929 cell culture infected with Chlamydia]. AB - The effect of the intracellular parasite Chlamydia trachomatis on the host cell energy metabolism has been studied. Glucose consumption by L-929 cell cultures infected or uninfected by C. trachomatis was studied in comparison during a 3 days cultivation. The content of glucose in the cultural medium was determined every 5, 24, 48, 72 hrs according to the developmental cycle of the parasite. It was shown that cell infection by C. trachomatis induced the alteration of energy metabolism via an increase in the glucose consumption rate. PMID- 1861658 TI - Patients go home for care. But do their doctors make house calls? AB - Caring for a patient at home no longer consists simply of a black bag and a stethoscope warmed in the physician's palm. No longer is it a quarantine sign the physician tacked up on the front door, or a thermometer and an injection of penicillin. Today, taking care of a patient at home often involves sophisticated equipment, a highly trained staff of nurses and allied professionals, and a set of skills and a body of knowledge with which many physicians are neither familiar nor comfortable. PMID- 1861659 TI - Chronic fatigue syndrome in Minnesota. AB - Chronic fatigue syndrome (CFS), an illness characterized by debilitating fatigue and a number of associated symptoms, was identified in 135 patients using the case definition provided in 1988. The demographic features of these patients, 97% of whom resided in Minnesota, were similar to those reported elsewhere. About three-fourths of the cases occurred between 1984 and 1989, and in 123 (91.1%), the illness began with what appeared to be an acute infection. Patients had been ill for an average of 4.3 years before enrollment in the study. Fatigue was their most troublesome symptom, although a majority of the patients rated most of the general symptoms and neuropsychological complaints associated with CFS as moderate or severe. Follow-up data obtained on 62 patients one year after initial evaluation revealed that none had completely recovered. However, about 40% reported some improvement in each of the CFS symptoms. PMID- 1861660 TI - Group G streptococcal purulent pericarditis. A case report. AB - We report one of the first two cases of group G streptococcal purulent pericarditis in the medical literature. Our experience illustrates that outcome for patients with this serious group G streptococcal infection may be poor. Failure of single-drug antibiotic therapy can occur, and we conclude that aggressive drainage and combination antibiotics are the most appropriate response to this potentially fatal infection. PMID- 1861661 TI - Medicare and Medicaid fraud and abuse regulation. Hanlester case provides hope for joint ventures. PMID- 1861662 TI - Qualified retirement plans. Yours may be worth just 17 on the dollar. AB - In summary, let's review the result of the Joneses' coordinated retirement income and estate planning strategy: 1. The Joneses maximized their estate assets, converting an inefficient estate asset to an efficient estate asset, without jeopardizing their current or future standard of living. 2. They committed to a gifting program for only 10 years, after which they have the flexibility to continue gifting the trust or to retain all the current IRA income. 3. They are free to "consume" their other taxable assets during their lifetimes without worrying about saving something for their three children. The Wealth Replacement Trust will leave approximately $1 million for each child. This strategy is obviously not available to everyone, nor is it applicable to everyone. While this solution worked extremely well for these clients, everyone's situation is different. Every situation needs a professional and personalized plan based upon individual objectives. Only after objectives have been clearly identified and alternatives thoroughly explored can a suitable solution be identified. It is important that a thorough review of the entire financial picture be performed by a competent financial planning team before you attempt to correct a potential problem. Make certain your advisers are familiar with solving this type of problem so as not to create additional problems. PMID- 1861663 TI - MMA grapples with AIDS-testing policy. PMID- 1861664 TI - HIV in mothers and infants. PMID- 1861665 TI - Body's first attack slows AIDS. PMID- 1861666 TI - Women fail to see AIDS risk. PMID- 1861667 TI - Reaping the rewards of rural practice. PMID- 1861668 TI - Eastern equine encephalitis--Florida, eastern United States, 1991. AB - The Florida Department of Health and Rehabilitative Services (HRS) has confirmed five human cases of eastern equine encephalitis (EEE) in elderly residents of Bradford, Duval, and Washington counties in northern Florida. Dates of illness onset were in mid-June and early July. One patient partially recovered and has residual neurologic deficits, two patients remain comatose, and two patients died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861669 TI - Trends in traumatic spinal cord injury--New York, 1982-1988. AB - In the United States, injuries resulting from falls are the most common type of injury among persons greater than or equal to 65 years of age, and most spinal cord injuries (SCIs) among persons in this age group are caused by falls. SCI, with its resultant paralysis, is one of the most catastrophic and devastating medical conditions. Previous studies have characterized the epidemiology of SCI. This report describes changes in the reported incidence of SCI in New York during 1982-1988.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861670 TI - Assessment of broadcast media airings of AIDS-related public service announcements--United States, 1987-1990. AB - Television and radio public service announcements (PSAs) are an integral part of acquired immunodeficiency syndrome (AIDS) public information campaigns. This report summarizes an assessment of airings of AIDS PSAs in the United States during October 1987-December 1990 that were produced by CDC's "America Responds to AIDS" (ARTA) campaign and other groups.* The assessment used data obtained from Broadcast Advertisers Reports (BAR) of the Arbitron Company. PMID- 1861671 TI - Multistate outbreak of Salmonella poona infections--United States and Canada, 1991. AB - During June and July 1991, more than 400 laboratory-confirmed infections with Salmonella poona occurred in 23 states and in Canada. This report describes several investigations that indicated this was a large nationwide outbreak related to consumption of cantaloupes. PMID- 1861672 TI - Pseudo-outbreak of infectious mononucleosis--Puerto Rico, 1990. AB - From September 11 through October 7, 1990, 57 persons (including outpatients, inpatients, and staff) at a community hospital in Puerto Rico had laboratory confirmed infectious mononucleosis; however, investigation determined that test results may have been misinterpreted. This report describes the investigation of this pseudo-outbreak by the Puerto Rico Department of Health (PRDH) in October 1990. PMID- 1861673 TI - County data on alcohol-related mortality--United States. AB - Although estimates of alcohol-related mortality (ARM) have been determined for the United States and selected states, the magnitude of ARM ahs not been well defined for smaller geographic areas. To provide additional geographically specific data, the Alcohol Epidemiologic Data System of the National Institute on Alcohol Abuse and Alcoholism recently released a reference manual for ARM in U.S. counties (County Alcohol Problem Indicators). The manual provides information for 3107 counties for 1979-1985 using both underlying and multiple cause-of-death information. This report summarizes data sources, methods, and applications for the manual. PMID- 1861674 TI - Nature of the intrinsic protein kinases involved in phosphorylation of non histone proteins in intact prostatic nuclei: further identification of androgen sensitive protein kinase reactions. AB - Nuclei isolated from rat ventral prostate contain a number of messenger-dependent and -independent protein kinases. Studies were undertaken to determine the relative contribution of these protein kinases in phosphorylation of non-histone proteins (NHPs) in isolated nuclei. The data suggest that messenger-dependent protein kinases such as those dependent on cAMP or Ca2+/calmodulin or Ca2+/phospholipid may be present in very small amounts in intact isolated nuclei, and thus appear not to be significantly involved in phosphorylation of endogenous NHPs. Messenger-independent nuclear associated protein kinases PK-N1 and PK-N2 are known to catalyze the phosphorylation of NHPs in vitro (Goueli Sa, et al., Eur J Biochem 113: 45-51, 1980). Of these, the intrinsic heparin-sensitive PK-N2 as compared with heparin-insensitive PK-N1 appeared to be the predominant protein kinase engaged in phosphorylation of NHPs in intact nuclei. About 78-88% of NHP phosphorylation in intact nuclei was inhibited by heparin suggesting that the remaining 12-22% phosphorylation of NHPs was catalyzed via the heparin insensitive protein kinase(s). Further, the data provide additional evidence that heparin-sensitive PK-N2 is the one that is most responsive to androgenic status in the animal. PMID- 1861675 TI - Metals are directly involved in the redox interconversion of Saccharomyces cerevisiae glutathione reductase. AB - Redox inactivation of glutathione reductase involves metal cations, since chelators protected against NADPH-inactivation, 3 microM EDTA or 10 microM DETAPAC yielding full protection. Ag+, Zn2+ and Cd2+ potentiated the redox inactivation promoted by NADPH alone, while Cr3+, Fe2+, Fe3+, Cu+, and Cu2+ protected the enzyme. The Zn2+ and Cd2+ effect was time-dependent, unlike conventional inhibition. Glutathione reductase interconversion did not require dioxygen, excluding participation of active oxygen species produced by NADPH and metal cations. One Zn2+ ion was required per enzyme subunit to yield full NADPH inactivation, the enzyme being reactivated by EDTA. Redox inactivation of glutathione reductase could arise from the blocking of the dithiol formed at the active site of the reduced enzyme by metal cations, like Zn2+ or Cd2+. The glutathione reductase activity of yeast cell-free extracts was rapidly inactivated by low NADPH or moderate NADH concentrations; NADP+ also promoted rapid inactivation in fresh extracts, probably after reduction to NADPH. Full inactivation was obtained in cell-free extracts incubated with glucose-6 phosphate or 6-phosphogluconate; the inactivating efficiency of several oxidizable substrates was directly proportional to the specific activities of the corresponding dehydrogenases, confirming that redox inactivation derives from NADPH formed in vitro. PMID- 1861676 TI - Nucleosomal organization of chromatin in sperm nuclei of the bivalve mollusc Aulacomya ater. AB - The sperm nuclei of Aulacomya ater, family Mitylidae, contain three proteins (X, Aa5 and Aa6) which are specific to this cell type coexisting with a set of five somatic-type histones. Information about the chromatin structure resulting from this kind of association is scarce. Therefore, we have probed the structure of this sperm chromatin through digestion with micrococcal nuclease in combination with salt fractionation. The data obtained have allowed us to propose a nucleosomal arrangement for this chromatin. However, two types of nucleosomes would be present in agreement with their protein components. PMID- 1861677 TI - Binding of the human complement subcomponent C1q to hybrid mouse monoclonal antibodies. AB - Activation of the classical pathway of the complement system is initiated by the binding of C1q to antibody complexes. Here we evaluated the C1q binding capacity of series of monospecific and bispecific hybrid mouse monoclonal antibodies (mAb) and compared them with parental (conventional) mAb. The hierarchy in C1q binding capacity of the bispecific anti-HuIgA1/HRP mAb with homologous H-H chain combinations (IgG2a-2a, IgG2b-2b and IgG1-1) and the parental anti-HuIgA1 or anti HRP mAb was identical; IgG2a greater than IgG2b much greater than IgG1. Hybrid IgG1-2a mAb bind intermediate amounts of C1q when compared with the IgG1 and IgG2a parental antibodies. IgG1-2b and IgG1-1 hybrid mAb did not bind any C1q, like the IgG1 mAb. We could not observe any difference in C1q binding efficiency between monovalently bound IgG1-2a, IgG2a-2a and IgG2b-2b anti-HuIgA1 HRP mAb and the bivalently bound IgG1-2a, IgG2a-2a and IgG2b-2b anti-HuIgA1 mAb, respectively. Furthermore, these hybrid ms anti-HuIgA1 and bs anti-HRP/HuIgA1 mAb were able to lyse HuIgA1-coated erythrocytes, in the presence of 50% human serum, as efficiently as their parental counterparts. These data indicate that a simultaneous binding of both F(ab') fragment to antigen is not a necessary prerequisite for binding and activation of C1q. PMID- 1861678 TI - Purification and biochemical characterization of an invertebrate interleukin 1. AB - Interleukin 1 (IL-1) is a major immunoregulatory protein released by macrophages with many host defense related properties. That IL-1 has been found in the invertebrates attests to its importance in homeostasis. The first step in comparing the vertebrate protein to its invertebrate correlate is to purify the protein to study. We have purified to homogeneity IL-1 isolated from the coelomic fluid of the starfish Asterias forbesi. The IL-1 had isoelectric points of 7.4, 5.4 and 4.8. The pI 4.8 species had a molecular weight of 22,000 and the pI 7.4 and 5.4 species both had Mr of 17,000. Higher Mr forms were also found. These molecules were biologically active in the human melanoma A375 cytotoxicity assay for IL-1, and were also able to stimulate murine dermal fibroblast proliferation, protein synthesis, and PGE2 production. The pI 4.8 and 5.4 forms were purified to homogeneity and the amino acid composition was determined. The pI 4.8 and 5.4 species were purified more than 200-fold to specific activities of 3 x 10(6) and 1 x 10(6) units mg-1, respectively. The pI 7.4 form was isolated and partial N terminal sequence analysis was performed. The similarities of molecular weight, isoelectric points and biological properties between vertebrate and invertebrate IL-1 show that it is an important, evolutionarily stable host defense molecule. PMID- 1861679 TI - Chemically unambiguous peptide immunogen: preparation, orientation and antigenicity of purified peptide conjugated to the multiple antigen peptide system. AB - We described a novel and simple approach to prepare chemically unambiguous peptide immunogen using the multiple antigen peptide (MAP) approach. This approach requires the conjugation of two purified components: a chloroacetylated oligomeric lysine core matrix and a synthetic peptide containing cysteine at either the carboxyl or amino terminus. The resulting MAP is structurally unambiguous and contains a quantifiable amount of peptide antigens. Furthermore, this method also provides a flexible strategy to link a peptide antigen to the core matrix at the desirable orientation to mimic the native molecule. The carboxyl fragment 43-50 of human transforming growth factor alpha (TGF alpha) was used as a test model for this approach. Antipeptide antibodies did not recognize the "reverse immunogen" in which the peptide was attached to the MAP core matrix at a reverse orientation. To determine the specificity of the antibodies, we used two series of point-substituted TGF alpha analogs containing either alanine or the corresponding D-amino acid replacement to map the antigenic site. The alanine analogs were used to determine the contribution of the side chain while the D amino acid analogs were used to determine the importance of backbone conformation. The antigen site was found to consist of four residues (Asp47-Leu48 Leu49-Ala50) at the distal end of the peptide-MAP conjugate. The results provide a clear explanation for the specificity of the antipeptide antibodies and their failure to recognize the "reverse immunogen" since the distal and the flexible end of the peptide-MAP construct constitutes the antigenic site. Furthermore, our results also suggests a strategy of placing the antigenic portion of a short peptide at the distal end in the MAP approach to prepare immunogen. PMID- 1861680 TI - Mechanism of allergic cross-reactions--II. Cross-stimulation, by chemically unrelated ligands, of rat basophilic leukemia cells sensitized with an anti-DNP IgE antibody. AB - Serotonin release from rat basophilic leukemia (RBL) cells, sensitized with a DNP binding monoclonal IgE, was stimulated with solid surface (polystyrene)-bound DNP amino acids. The stimulatory potency of DNP-amino acids was dependent on the structure of amino acid attached to DNP. Generally, DNP-amino acids with high affinities to the sensitizing IgE (I(50) less than 10 microM) were stimulatory in polystyrene-bound form; DNP-amino acids with lower affinities (Pro, Cys, Trp), and aliphatic aromatic DNP-amino acid derivatives were inactive. In addition to structural analogues of DNP, lymecycline, that is chemically unrelated to DNP but was found to have high affinity to IgE(aDNP), was also stimulatory in this system. This drug, and various quinones (e.g. acenaphthene-quinone) in BSA conjugated forms also stimulated serotonin release from RBL cells sensitized with IgE(aDNP). These studies suggest that (1) There is a threshold of intrinsic ligand binding affinities at approximately I(50) = 10-100 microM; ligands with lower affinities do not stimulate mediator release even if they are presented in multivalent forms; (2) The above affinity threshold for mediator cell stimulation is valid for various ligands, irrespective of their chemical similarity to the immunogen; (3) Multispecific stimulation of mediator release may contribute to the frequently observed allergic cross-reactions, false positive tests for allergies, and anaphylactic reactions to drugs upon first exposure. PMID- 1861681 TI - Isolation and partial characterization of a type IV bacterial immunoglobulin binding protein. AB - A series of bovine G streptococcal isolates were screened for expression of type IV Fc binding proteins. An isolate expressing high levels of type IV binding proteins was selected and expanded by use of a colony selection technique. A variety of different extraction procedures were compared and the optimal solubilization procedure was found to be hot acid extraction of the bacteria. The extracted protein could be affinity purified on a column of immobilized rabbit IgG. The type IV Fc binding protein was found to be antigenically unrelated to the type I, II or III bacterial Fc binding proteins and displayed the lowest affinity and most limited range of species and subclass reactivity of any bacterial Fc binding protein thus far characterized. PMID- 1861682 TI - Isolation and characterization of a monoclonal rheumatoid factor specific for the hinge region of rat IgG2b. AB - The isolation and characterization of an isotype-specific autoantibody-secreting hybridoma NET/2/3 from rats bearing the syngeneic tumour HSN is described. This rheumatoid factor of the IgM class recognizes an epitope within the hinge region of rat immunoglobulins of the IgG2b subclass which is destroyed by reduction of disulphide bonds. The specificity of NET/2/3, although not allotype-restricted, is highly isotype-restricted, as it does not bind to rat Ig other than IgG2b, nor does it react with the majority of mouse IgG, although some reactivity occurs with mouse IgG3. One remarkable feature of NET 2/3 is that it binds more strongly to F(ab')2 and Fab' fragments of rat IgG2b, obtained by digestion with pepsin, than to the whole molecule. This anti-isotype response is not peculiar to the HSN tumour model as NET/2/3-like antibodies have been found in the sera of rats immunized with various protein and cellular antigens. The possible biological role of this anti-isotype antibody is discussed. PMID- 1861683 TI - Human lymphocytes exposed to low doses of X-rays are less susceptible to radiation-induced mutagenesis. AB - Human lymphocytes exposed to low doses of X-rays become refractory to the subsequent induction of chromosomal damage by high doses of radiation (Shadley and Wolff, 1987). The current study was designed to test the effect of pretreatment of human T-lymphocytes with a low dose of X-rays on the induction of mutations at the hprt locus by a subsequent challenge dose. When cells were exposed to 1 cGy X-rays 24 h after phytohemagglutinin stimulation, the yield of mutations induced by a 300 cGy X-ray dose given 16 h later was reduced by approximately 70% from the control level of X-ray-induced mutations. This indicates that this previously described adaptive response to low dose X-rays also results in lymphocytes becoming refractory to the induction of gene mutations. PMID- 1861684 TI - Cycloheximide genotoxicity in in vitro and in vivo test systems. AB - The aim of this study was to investigate if there was any genotoxic effect produced by the antibiotic cycloheximide, widely used as a fungicide in agriculture as well as in everyday laboratory practice. The battery of test systems included the bacterium Salmonella typhimurium (strains TA98 and TA100), the yeast Saccharomyces cerevisiae (D7), Allium cepa somatic cells and mouse bone marrow cells. This combination of test systems enabled us to establish possible effects caused by cycloheximide at different levels of the genome and to indicate a possible mechanism of action. The results obtained in experiments showed that cycloheximide did not induce frameshift or base-pair substitution mutations in S. typhimurium regardless of metabolic activation. In S. cerevisiae cycloheximide had only toxic effects but no increase of mitotic gene conversion was noticed under the conditions of the experiment. However, in A. cepa somatic cells as well as in mouse bone marrow cells cycloheximide showed its activity causing different genetic damages, e.g., chromosome breaks, mitotic disturbances and nuclear abnormalities. PMID- 1861685 TI - Transformation of Saccharomyces cerevisiae with UV-irradiated single-stranded plasmid. AB - UV-irradiated single-stranded replicative plasmids were used to transform different yeast strains. The low doses of UV used in this study (10-75 J/m2) caused a significant decrease in the transforming efficiency of plasmid DNA in the Rad+ strain, while they had no effect on transformation with double-stranded plasmids of comparable size. Neither the rev3 mutation, nor the rad18 or rad52 mutations influenced the efficiency of transformation with irradiated single stranded plasmid. However, it was found to be decreased in the double rev3 rad52 mutant. Extracellular irradiation of plasmid that contains both URA3 and LEU2 genes (psLU) gave rise to up to 5% Leu- transformants among selected Ura+ ones in the repair-proficient strain. Induction of Leu- transformants was dose-dependent and only partially depressed in the rev3 mutant. These results suggest that both mutagenic and recombinational repair processes operate on UV-damaged single stranded DNA in yeast. PMID- 1861686 TI - Damage distribution and mutation spectrum: the case of 8-methoxypsoralen plus UVA in mammalian cells. AB - We determined the distribution of monoadducts and biadducts induced in the supF tRNA gene carried by the shuttle vector pZ189, after exposure to 8 methoxypsoralen (8-MOP) plus a double UVA (365 nm) irradiation. These data were compared to our previously published 8-MOP-photoinduced mutation spectrum obtained after propagation of the damaged shuttle vector in mammalian cells. One mutational hot spot in an ATAT/TATA sequence is targeted at a hot spot of biaddition. A second hot spot is not related to the presence of photoadducts either at or near the site. Moreover, it is located in a sequence which can be defined as 'mutation-prone'. Mutations occurring at GC base pairs are not targeted at sites of photoaddition, and may result from a decrease in fidelity of DNA polymerase when copying the damaged vector. PMID- 1861687 TI - Clastogenic effects of hydroquinone: induction of chromosomal aberrations in mouse germ cells. AB - The clastogenic activity of hydroquinone (HQ) in germ cells of male mice was evaluated by analysis of chromosomal aberrations in primary spermatocytes and differentiating spermatogonia. In the first experiment with treated spermatocytes the most sensitive stage of meiotic prophase to aberration induction by HQ was determined. Testicular material was sampled for microscopic analysis of cells in diakinesis-metaphase I at 1, 5, 9, 11, and 12 days after treatment with 80 mg/kg of HQ, corresponding to treated diplotene, pachytene, zygotene, leptotene and preleptotene. The frequencies of cells with structural chromosome aberrations peaked at 12 days after treatment (p less than 0.01). This indicates that the preleptotene when DNA synthesis occurred was the most sensitive stage of meiotic prophase. In the second experiment the dose response was determined 12 days post treatment by applying 2 additional doses of 40 mg/kg and 120 mg/kg. The clastogenic effects induced by 40 and 80 mg/kg were significantly different from the controls (p less than or equal to 0.01) and higher than the results obtained with 120 mg/kg of HQ. A humped dose-effect relationship was observed. In a third experiment the same doses were used to analyse chromosomal aberrations in dividing spermatogonia of mice 24 h after treatment with HQ. All the administered doses gave results statistically different from the control values (p less than or equal to 0.01) and the data were fitted to a linear equation. HQ was found to be clastogenic in male mouse germ cells. It is concluded that the clastogenic effect in male germ cells is of the same order of magnitude as in mouse bone marrow cells. PMID- 1861688 TI - Clastogenic and aneuploidizing effects of antiblastic busulphan revealed by kinetochore immunofluorescence in CHO cells. AB - We utilized, in CHO cells, the cytoplasm preservation technique to evaluate the micronucleus frequency at different busulphan concentrations, and the indirect immunofluorescence technique, using sera obtained from patients with scleroderma (CREST variant), to analyze if busulphan-induced micronuclei have kinetochores. Results show that this alkylating agent is capable of causing a significant increase of micronuclei in vitro, a great part (40%) of them having CREST positive kinetochores. These findings confirm the clastogenic effect of busulphan and reveal a considerable capability of this agent to induce aneuploidy. These results are examined taking into account the high incidence of secondary neoplasias induced by chemotherapy with alkylating agents utilized against primary neoplasias. PMID- 1861689 TI - Micronuclei in lymphocytes of young patients under antileukemic therapy. AB - The micronucleus test in peripheral blood lymphocytes was employed in the cytogenetic monitoring of children with acute lymphocytic leukemia (ALL), who had undergone chemotherapy and radiotherapy. Patients were treated with a variety of drugs, which included vincristine, methotrexate, daunomycin and prednisone; they also underwent cranial irradiation at the end of the first intensive phase of therapy. The first group under study consisted of 15 subjects on therapy, who showed a marked increase in micronucleated lymphocytes (mean: 19.96 +/- 12.96%) as a consequence of treatment compared with the control group (mean: 3.67 +/- 1.55%), while lower average values were obtained from 15 other subjects at the end of treatment (mean: 13.16 +/- 8.44%). A group of 6 patients was monitored during the entire period of therapy, namely at diagnosis, after 3 months of therapy, throughout maintenance therapy and at the end of it. The whole treatment lasted about 2 years. The results revealed a marked increase in basal micronucleus frequency, due to therapy: the micronucleated lymphocyte frequency remained significantly high throughout the treatment for almost all patients. These data clearly suggest the validity of the methodology in pointing out the role played by antileukemic agents in inducing somatic genetic damage. PMID- 1861691 TI - Chemical induction of somatic gene mutations and chromosomal aberrations in lung fibroblasts of rats. AB - Rats can be used to detect both somatic gene mutations and chromosomal aberrations induced in vivo. The technique adapted from Chinese hamsters for the isolation and analysis of lung fibroblasts confirm the surprising results obtained in hamsters; namely, methyl methanesulphonate induces many micronuclei but no significant increase in gene mutations. In contrast ethylnitrosourea induces both micronuclei and gene mutations. PMID- 1861690 TI - Activation of some aromatic amines to mutagenic products by human red blood cell cytosol. AB - The ability of human red blood cell cytosol to activate aromatic amines was evaluated with the Ames test using Salmonella typhimurium TA98 in the liquid preincubation condition. While negative results were obtained with 4 acetylaminofluorene (4AAF) and 1-naphtylamine (1NA), a slight response was observed for 4-aminobiphenyl (4ABP) and 2-naphthylamine (2NA). Human red blood cell cytosol was able to activate 2-aminofluorene (2AF), 2-acetylaminofluorene (2AAF) and 2-aminoanthracene (2AA) to mutagenic intermediates. Extracts of human red blood cell cytosol incubated with 2AF were analyzed by gas chromatography: N hydroxy-2-aminofluorene was identified as a metabolite. PMID- 1861692 TI - Effects of diethylstilbestrol and its methyl ethers on aneuploidy induction and microtubule distribution in Chinese hamster V79 cells. AB - We previously reported that diethylstibestrol (DES) and its derivatives inhibit the in vitro polymerization of microtubule proteins isolated from porcine brain (Sato et al., 1987). We found that the presence of the free hydroxy group of DES was indispensable for the inhibition of microtubule assembly. In the present investigation, this structure-activity relationship was confirmed by the effects of DES and its methyl ethers on chromosome number and the cellular microtubule architecture of Chinese hamster V79 cells, revealed by fluorescent anti-tubulin antibody. DES induced tetra- and octa-ploidy and DES monomethyl ether induced only tetraploidy at a much slower rate, whereas DES dimethyl ether was found to be completely inactive. Furthermore, DES was more active than its monomethyl ether in disturbing microtubule formation within cells. These results support the initial assumption that polyploidy is largely a consequence of the disturbed assembly of microtubules. PMID- 1861693 TI - Thyroid diseases after treatment of Hodgkin's disease. AB - BACKGROUND AND METHODS: Thyroid disease, especially hypothyroidism, is common in patients with Hodgkin's disease who have been treated with irradiation. We reviewed the records of 1787 patients (740 women and 1047 men) with Hodgkin's disease who were treated with radiation therapy alone (810 patients), radiation and chemotherapy (920 patients), or chemotherapy alone (57 patients) at Stanford University between 1961 and 1989. Among these patients, 1533 were alive at the last follow-up, and 254 had died of causes other than Hodgkin's disease. (Four other patients were excluded from the analysis because they had undergone thyroidectomy before treatment for Hodgkin's disease. The thyroid was irradiated in 1677 patients. Follow-up averaged 9.9 years. RESULTS: A total of 573 patients had clinical or biochemical evidence of thyroid disease. Among the 1677 patients whose thyroid was irradiated, the actuarial risk of thyroid disease 20 years after treatment was 52 percent, and it was 67 percent at 26 years. Hypothyroidism was found in 513 patients. A total of 486 patients received thyroxine therapy for elevated serum thyrotropin concentrations and either low free thyroxine (208 patients) or normal free thyroxine values (278 patients); 27 had transient elevations of the serum thyrotropin level that were not treated. Graves' hyperthyroidism developed in 30 patients (2 of whom had not undergone thyroid irradiation), and ophthalmopathy developed in 17 of these patients. Ophthalmopathy developed in four other patients with Graves' disease during a period of hypothyroidism (n = 3) or euthyroidism (n = 1). The risk of Graves' disease was 7.2 to 20.4 times that for normal subjects. Silent thyroiditis with thyrotoxicosis developed in six patients. Forty-four patients were found to have single or multiple thyroid nodules, 26 of whom underwent thyroidectomy. Six of the 44 had papillary or follicular cancers. Among the patients who did not undergo operation, 12 had small functioning nodules, 4 had cysts, and 2 had multinodular goiters. The actuarial risk of thyroid cancer was 1.7 percent. The risk of thyroid cancer was 15.6 times the expected risk. CONCLUSIONS: High risks of thyroid disease persist more than 25 years after patients have received radiation therapy for Hodgkin's disease, reinforcing the need for continued clinical and biochemical evaluation. Prolonged follow-up confirms an elevated risk of thyroid cancer and Graves' disease as well as hypothyroidism in these patients. PMID- 1861694 TI - Long-term response of recurrent respiratory papillomatosis to treatment with lymphoblastoid interferon alfa-N1. Papilloma Study Group. AB - BACKGROUND: We earlier reported that patients with recurrent respiratory papillomatosis responded to six months of treatment with lymphoblastoid interferon alfa-n1. Because another study of patients treated for one year with leukocyte interferon alfa-n3 found that the growth rate of papillomas was slowed in the first six months but returned to base line during months 7 through 12 despite persistent interferon treatment, we now report the long-term results in our original study patients who were followed for a median of four years after the original one-year crossover study. METHODS: After the patients in our study had completed the first study year, their physicians could continue or recommence treatment with lymphoblastoid interferon alfa-n1 in a dose of either 2 MU per square meter of body-surface area per day or 4 MU per square meter every other day. The extent of disease was measured by endoscopy when clinically indicated. RESULTS: Data on late-follow-up were obtained for 60 of the 66 patients. There were 22 complete remissions and 25 partial remissions; 13 patients had no response. The median duration of the complete remissions was 550 days, and 15 patients continued to be in complete remission. The median duration of partial remissions was 400 days and seven patients were still in partial remission. Thirteen of 28 patients responded to a second course of interferon after an interruption in treatment of at least one month. The rate of response in the 11 of 53 patients who had neutralizing antibody to interferon was the same as in the patients without the antibody. CONCLUSIONS: Patients with severe recurrent respiratory papillomatosis may have a sustained or repeated response to treatment with lymphoblastoid interferon alfa-n1. We recommend that patients with recurrent respiratory papillomatosis who require surgery every two to three months be given a six-month trial of interferon alfa-n1. PMID- 1861696 TI - Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. PMID- 1861695 TI - Evidence of a selective increase in cardiac sympathetic activity in patients with sustained ventricular arrhythmias. AB - BACKGROUND: Although enhanced efferent cardiac sympathetic nervous activity has been proposed as an important factor in the genesis of ventricular arrhythmias and sudden cardiac death, direct clinical evidence has been lacking. METHODS: We measured the rates of total and cardiac norepinephrine spillover into the plasma, which reflect respectively overall and cardiac sympathetic nervous activity, in 12 patients who had recovered from a spontaneous, sustained episode of ventricular tachycardia or ventricular fibrillation outside the hospital 4 to 48 days earlier. The results were compared with those from three age-matched reference groups without a history of ventricular arrhythmias: 12 patients with coronary artery disease, 6 patients with chest pain but normal coronary arteries, and 12 healthy, normal subjects. RESULTS: The patients who had had ventricular arrhythmias had reduced left ventricular ejection fractions, as compared with the patients with coronary artery disease or chest pain (mean [+/- SE], 46 +/- 3 percent vs. 58 +/- 4 percent and 69 +/- 5 percent, respectively; P less than 0.003). The rates of total norepinephrine spillover into the plasma were similar in the three reference groups, but 80 percent higher in the patients with ventricular arrhythmias (P less than 0.005). The rate of cardiac norepinephrine spillover was 450 percent higher in these patients (176 +/- 39 pmol per minute, as compared with 32 +/- 8 pmol per minute in the normal subjects; P less than 0.001), a disproportionate increase relative to the increase in total spillover, which indicated selective activation of the cardiac sympathetic outflow. This increase in cardiac norepinephrine spillover was probably caused by a reduction in left ventricular function. CONCLUSIONS: These results suggest that in some patients major ventricular arrhythmias are associated with and perhaps caused by sustained and selective cardiac sympathetic activation. We speculate that depressed ventricular function was present before the ventricular arrhythmia occurred, and that this resulted in reflex cardiac sympathetic activation, which in turn contributed to the genesis of the arrhythmia. PMID- 1861697 TI - The pharmacologic treatment of depression. PMID- 1861698 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 35-1991. A 59-year-old man with abdominal pain, microscopic hematuria, and a jejunal abnormality shown on a CT scan. PMID- 1861699 TI - In the vertical transmission of HIV, timing may be everything. PMID- 1861700 TI - Stress and the common cold. PMID- 1861701 TI - Sympathetic stimulation and arrhythmias. PMID- 1861702 TI - Death and dignity: the case of Diane. PMID- 1861703 TI - More on the treatment of end-stage renal disease. PMID- 1861704 TI - Pneumocystis carinii pneumonia developing within one month of intensive chemotherapy for treatment of acute lymphoblastic leukemia. PMID- 1861705 TI - Long-term survivors of refractory myelodysplastic anemias. PMID- 1861706 TI - Milk-contaminated "nondairy" products. PMID- 1861707 TI - Electroconvulsive therapy in a patient with a heart transplant. PMID- 1861708 TI - Spina bifida in infants of women taking carbamazepine. PMID- 1861709 TI - Ethical problems to merit the name. PMID- 1861710 TI - Cetus and Chiron merge. PMID- 1861712 TI - Japan. Neuroscience leads grants. PMID- 1861711 TI - Biotechnology. A first step, but still a long way to go. PMID- 1861713 TI - Bacon's chicken. PMID- 1861714 TI - Genome ethics treaty. PMID- 1861715 TI - AIDS. Passive primate protection. PMID- 1861716 TI - Helix formation. Alarums and diversions. PMID- 1861717 TI - Identification of a murder victim by DNA analysis. PMID- 1861718 TI - Ancient DNA. The past comes alive. PMID- 1861719 TI - Lead risks. PMID- 1861720 TI - Multiple modes of engrailed regulation in the progression towards cell fate determination. AB - The engrailed gene product of Drosophila specifies the fate of a subset of cells in each segment. Our studies of engrailed regulation suggest that fate determination is an elaborate, multistep process. At the time in embryogenesis when the engrailed-dependent cell fate is probably determined, four modes of control act in an overlapping progression to govern engrailed expression. After activation by pair-rule genes, both an extracellular signal, wingless, and autoregulation are required for engrailed expression. Autoregulation graduates to wingless independence, but is transient, and is superseded by an engrailed independent mode of maintenance. PMID- 1861721 TI - Identification of the skeletal remains of a murder victim by DNA analysis. AB - There is considerable anthropological and forensic interest in the possibility of DNA typing skeletal remains. Trace amounts of DNA can be recovered even from 5,500-year-old bones and multicopy human mitochondrial DNA sequences can frequently be amplified from such DNA using the polymerase chain reaction (PCR). But given the sensitivity of PCR, it is very difficult to exclude contaminating material. We now report the successful identification of the 8-year-old skeletal remains of a murder victim, by comparative typing of nuclear microsatellite markers in the remains and in the presumptive parents of the victim. This analysis establishes the authenticity of the bone DNA and the feasibility of bone DNA typing in forensic investigations. PMID- 1861722 TI - Fibronectin and VLA-4 in haematopoietic stem cell-microenvironment interactions. AB - The self-renewal and differentiation of haematopoietic stem cells occurs in vivo and in vitro in direct contact with cells making up the haematopoietic microenvironment. In this study we used adhesive ligands and blocking antibodies to identify stromal cell-derived extracellular matrix proteins involved in promoting attachment of murine haematopoietic stem cells. Here we report that day 12 colony-forming-unit spleen (CFU-S12)5 cells and reconstituting haematopoietic stem cells attach to the C-terminal, heparin-binding fragment of fibronectin by recognizing the CS-1 peptide of the alternatively spliced non-type III connecting segment (IIICS) of human plasma fibronectin. Furthermore, CFU-S12 stem cells express the alpha 4 subunit of the VLA-4 integrin receptor, which is known to be a receptor for the CS-1 sequence, and monoclonal antibodies against the integrin alpha 4 subunit of VLA-4 block adhesion of CFU-S12 stem cells to plates coated with the C-terminal fibronectin fragment. Finally, polyclonal antibodies against the integrin beta 1 subunit of VLA-4 inhibit the formation of CFU-S12-derived spleen colonies and medullary haematopoiesis in vivo following intravenous infusion of antibody-treated bone marrow cells. PMID- 1861723 TI - A recycling pathway between the endoplasmic reticulum and the Golgi apparatus for retention of unassembled MHC class I molecules. AB - Assembly of class I major histocompatibility complex (MHC) molecules involves the interaction of two distinct polypeptides (the heavy and light chains) with peptide antigen. Cell lines synthesizing both chains but expressing low levels of MHC class I molecules on their surface as a result of a failure in assembly and transport have been identified. We now report that although the apparent steady state distribution in these cells of class I molecules is in the endoplasmic reticulum (ER), the molecules in fact are recycled between the ER and Golgi, rather than retained in the ER. This explains the failure of class I molecules to negotiate the secretory pathway. Class I molecules do not seem to be modified by Golgi enzymes, suggesting that the proteins do not reach the Golgi apparatus during recycling. But morphological and subcellular fractionation evidence indicates that they pass through the cis Golgi or a Golgi-associated organelle, which we postulate to be the recycling organelle. This compartment, which we call the 'cis-Golgi network', would thereby be a sorting organelle that selects proteins for return to the ER. PMID- 1861724 TI - Transcription by single molecules of RNA polymerase observed by light microscopy. AB - The kinetics of transcription by Escherichia coli RNA polymerase relate directly to the regulation of transcription and to the properties of processive enzymes in general, but analysis of RNA polymerase movement along the DNA template has so far been limited to the study of populations of enzyme molecules. The ability to view nanometre-sized particles with the light microscope suggested a method of monitoring transcription by individual RNA polymerase molecules. We describe here the behaviour of 40-nm-diameter particles of colloidal gold attached to the ends of DNA molecules being transcribed by RNA polymerase immobilized on a glass surface. The tethered gold particles are released from the surface at times after addition of nucleoside triphosphates that are consistent with the kinetics of transcription by RNA polymerase in solution. Analysis of the brownian motion of the gold particles enabled us to measure the movement along the template DNA of individual polymerase molecules. PMID- 1861725 TI - Accurate prediction of the stability and activity effects of site-directed mutagenesis on a protein core. AB - Theoretical prediction of the structure, stability and activity of proteins, an important unsolved problem in molecular biology, would be of use for guiding site directed mutagenesis and other protein-engineering techniques. X-ray diffraction studies have provided extensive structural information for many proteins, challenging theorists to develop reliable techniques able to use such knowledge as a base for prediction of mutants' characteristics. Here we report theoretical calculation of stabilization energies for 78 triple-site sequence variants of lambda repressor characterized experimentally by Lim and Sauer. The calculated energies correlate with the mutants' measured activities; active and inactive mutations are discriminated with 92% reliability. They correlate even more directly with the mutants' thermostabilities, correctly identifying two of the mutants to be more stable than the wild type. PMID- 1861726 TI - The helical s constant for alanine in water derived from template-nucleated helices. AB - Formation of alpha helices from disordered polypeptides depends on the degree to which amino acids favour the helical state. The folding of helical oligopeptides can be modelled by two parameters: sigma which reflects helix initiation and s which reflects propagation of a pre-existing helix and measures helical bias. Scheraga has reported s values for oligopeptides of about 1.1, implying a weak helical bias for amino-acid residues. By contrast, certain helical peptides studied by Baldwin seem to require much larger s values for alanine. Resolution of this inconsistency requires experiments that disentangle the ease of propagation from that of initiation. In this study varying lengths of polyalanine are linked to a 'template' that initiates helical structure and permits study solely of propagation. We report here that the s value for alanine in water is close to 1, supporting the earlier results of Scheraga but not the more recent results of Baldwin. PMID- 1861727 TI - The development of a comprehensive cancer center. A concerted effort spearheaded by Charles L. Spurr, M.D. PMID- 1861728 TI - Hospital infection control, seat belts and the national debt. PMID- 1861730 TI - Infant mortality. PMID- 1861729 TI - Kikuchi's disease. A benign disease of unknown etiology. PMID- 1861731 TI - Historical note: North Carolina's first hospital. PMID- 1861732 TI - Polio epidemic. PMID- 1861733 TI - Lightning fatalities in North Carolina 1972-1988. AB - Individuals who are outdoors during thunderstorms are at risk for death from direct and indirect lightning hits. Death is more likely from 3:00 p.m. to 8:00 p.m. during the months of May through September. The fatality pattern in North Carolina is similar to that reported for the nation as a whole. Physicians are urged to discuss with their patients simple strategies for reducing exposure to lightning. PMID- 1861735 TI - An open letter to Dr. Ralph E. Snyder of Medical Review of North Carolina, Inc. PMID- 1861734 TI - A comment on Dr. Burke's article on the red fire ant. PMID- 1861736 TI - [Metastasized Grawitz tumor: wonders never cease]. PMID- 1861737 TI - [Vitamin A requirement during pregnancy and lactation]. PMID- 1861738 TI - [Laboratory diagnosis in deep Candida infections]. PMID- 1861739 TI - [Spontaneous pneumothorax; to operate or not?]. AB - Disagreement remains on the best mode of therapy for spontaneous pneumothorax (SP). Treatment options vary from observation alone to thoracotomy depending on the stage of the disease and the preference of the physician. Between 1983 and 1988, 122 patients with SP were treated at the Elisabeth Hospital Tilburg according to a fixed protocol. Of these patients 86 (68%) were primarily treated with observation alone or with intercostal tubes. Seven of these patients (8%) had to be treated surgically after failure of the primary treatment. After thoracoscopical selection and in case of recurrent disease 39 patients underwent surgery: apical pleurectomy and bullectomy, in most cases by the transaxillary approach. In this group morbidity was minimal and there were no recurrences. We conclude that for most patients with spontaneous pneumothorax non-surgical therapy is the therapy of first choice. PMID- 1861740 TI - [Insufficient protection against infection with HIV in general and orthopedic surgeons]. AB - In a study of the content of occupational health care for hospital workers we carried out a separate study to measure the professional protection used to prevent contamination with HIV or hepatitis B virus. Therefore we carried out a study among Dutch general and orthopaedic surgeons. A questionnaire was sent to a representative sample of this population. The conclusions are that the respondents are relatively poorly informed about HIV and (or) hepatitis risks. A relatively small part of the respondents used protecting instruments; 40 (operating rooms) and 83% (emergency departments) of the respondents did not use safety glasses. The availability of protecting instruments is higher in operating rooms than in emergency departments, but this availability does not imply use of these instruments. The information on occupational contamination risks, the individual safety measures and the quality of the safety glasses are subject to criticism. PMID- 1861741 TI - [Relation between clinical condition and quality of life in patients on hemodialysis, a clinimetric study]. AB - To gain more insight into the quality of life of chronic haemodialysis patients, a clinimetric study was performed in 60 patients treated in a centre for active haemodialysis: Diatel, Amsterdam. The value of a number of objective and subjective test methods was also analysed. The mean age was 52 years, 57% were males and the mean time on dialysis treatment was 68 months. The objective tests were the Karnofsky index, the Active Clinical Problems Score and the Chemistry Abnormality Score. The data were obtained from the physician in charge and the medical record of the patient. The subjective information was gained during an interview based on the following tests: the Complaints score, Affect Balance Scale, Index of Well-being and Nottingham Health Profile. The physical condition of the patients depended on both age and comorbidity and was generally good; 6% of the patients had a Karnofsky score of less than or equal to 60. For the Index of Well-being patients scored lower than healthy people (p less than 0.01). The level of this index depended on age, employment and civil status. The subjective tests were significantly interrelated, the objective tests also but to a lesser extent. No correlations were found between the objective status of the patient and his emotional well-being. In conclusion, active haemodialysis patients appeared to have a fairly good quality of life. Of all tests the Affect Balance Scale, the Index of Well-being and the Complaints score were found to be the most useful, probably also for future longitudinal research. PMID- 1861742 TI - [Magnesium poisoning in an infant]. AB - We present the case of a girl aged 3 weeks with extreme hypermagnesaemia (7.94 mmol/l) due to an overdose of magnesium oxide, prescribed as a laxative. We treated her successfully with a combination of hyperhydration, forced diuresis and natriuresis, and additional intravenous calcium and insulin. We also performed an exchange transfusion which, however, had a questionable effect on the final outcome. PMID- 1861743 TI - [Extramural health care in AIDS: comparison between the United States and The Netherlands]. PMID- 1861744 TI - [How reliable is ocular pressure measurement, which device is the most accurate and what are the limits of normal values?]. PMID- 1861745 TI - [Reasons for refusal of articles for publication by the Nederlands Tijdschrift voor Geneeskunde in 1990]. PMID- 1861746 TI - [Minor symptoms in family practice; theory and practice in bursitis of the olecranon]. PMID- 1861747 TI - [Foreign reporting on side effects of drugs]. PMID- 1861748 TI - [The physician, the pharmacist and authoritative drug prescriptions]. PMID- 1861749 TI - [Collagenous colitis; an invisible disease?]. PMID- 1861750 TI - ['Only ergotamine still helps']. PMID- 1861751 TI - [Auxiliary heterotopic liver transplantation]. PMID- 1861752 TI - [Renal osteodystrophy]. PMID- 1861753 TI - [Determination of antibodies against double-stranded DNA; when and which test?]. PMID- 1861754 TI - [Favorable results of auxiliary heterotopic liver transplantation in patients with end-stage chronic liver insufficiency]. AB - Auxiliary heterotopic liver transplantation (HLT), which avoids removal of the host liver, may improve the results of liver transplantation in patients with end stage chronic liver disease. However, the results of HLT have so far been disappointing. In 1986 a program of HLT was started in the University Hospital Rotterdam-Dijkzigt. Eighteen patients with chronic liver failure underwent HLT. Twelve out of 18 (67%) patients were discharged 25 days after transplantation with normal liver function. Six patients died within 3 months after operation due to septic causes. Three months after transplantation ascites was no longer detectable and oesophageal varices had disappeared in all surviving recipients of HLT. The actuarial 3 and 12 months survival rate was 67%. Hepatitis B virus reinfection was seen in all patients. In two patients cirrhosis of the graft developed within one year. These data suggest that HLT in patients with chronic liver failure gives long-term metabolic support and adequate decompression of portal system, and is associated with a morbidity and mortality comparable to that of orthotopic liver transplantation. PMID- 1861755 TI - [Conservative therapy frequently indicated in blow-out fractures of the orbit]. AB - The results of the conservative approach in the management of patients with orbital blow-out fractures were studied at the Orbital Centre, Amsterdam. In 54 out of 111 patients with a pure blow-out fracture, high resolution CT was performed. In these 54 patients with diplopia, clinical examination together with the analysis of direct multiplanar high resolution CT revealed four cases of impaired motility. These were oedema, oculomotor nerve palsy, enophthalmos and adhesions around the lower eye muscles and the orbital floor. Patients were immediately instructed to exercise eye movements thoroughly. If diplopia did not resolve, further management was decided on. In all patients with edema or oculomotor nerve palsy, diplopia resolved spontaneously. Surgery was necessary to reduce diplopia in the enophthalmos and adhesion groups. This study shows that eye movement exercises together with a 'wait and see' approach diminish the number of operations by 50% in patients with pure blow-out fractures. It also circumvents the iatrogenic adhesions between eye muscles and orbital floor, which are difficult to treat. PMID- 1861756 TI - [11-year survival following aortocoronary bypass surgery]. AB - To evaluate longterm survival after a first aortocoronary bypass operation we followed up all such patients with operations between July 1971 and June 1980. Included were 1041 patients, mean follow-up time was 11 years (8.5-17.4). Data were complete in 98%. The perioperative mortality equalled 1.2%, survival probability at 5 and 10 years was 92% and 77%, respectively. The yearly mortality rate increased from the fifth year onward up to 5% in the tenth. Of the deceased patients 72% had a cardiac cause of death. Extent of vascular involvement, quality of left ventricular function and age at operation had an important influence on survival probability. The aortocoronary bypass operation is a safe procedure, with a good prognosis for survival, but does not prevent cardiac death in the future. PMID- 1861757 TI - [Liver transplantation in acute liver insufficiency: definitive replacement or auxiliary liver?]. AB - Orthotopic liver transplantation (OLT) has greatly improved the chances of survival in patients with acute hepatic failure. However, this mode of treatment requires lifelong immunosuppressive medication and negates the potential recovery of the host liver. In theory, auxiliary heterotopic liver transplantation (HLT) offers the diseased host liver a chance to regenerate, so that immunosuppression can be tapered off and eventually stopped. In the University Hospital Rotterdam Dijkzigt OLT and HLT were performed in two patients, with acute and subacute hepatic failure respectively. The patient undergoing OLT recovered quickly but needed a successful re-OLT after a serious rejection episode. The removed diseased liver showed no signs of regeneration at histology. The patient undergoing HLT also recovered well. HIDA scanning as well as liver biopsies of the host liver and the grafted liver 1 and 6 months after transplantation indicated full recovery of the host liver, so that immunosuppression is being tapered off. PMID- 1861758 TI - [Clozapine; an exceptional comeback]. PMID- 1861759 TI - [Scientific research and privacy]. PMID- 1861760 TI - [Bad news before childbirth; who will tell the parents?]. PMID- 1861761 TI - [Patellar chondropathy in family practice]. PMID- 1861762 TI - [Children with attention deficit disorders with hyperactivity; the role of drugs in treatment]. PMID- 1861763 TI - [Rhabdomyolysis]. PMID- 1861764 TI - [Little extra information with ultrasonic studies of the axillary glands in patients with breast carcinoma]. AB - In order to establish the value of ultrasound examination of the axillary lymph nodes on the presence of lymph node metastases of carcinoma of the breast a prospective survey was carried out in 100 consecutive patients with a carcinoma of the breast on which a lymph node dissection was performed. In the survey the results of the ultrasound examination were compared with the results of the physical and pathological examinations. Although the sensitivity of the ultrasound examination was higher (60%) than that of the physical examination (33%) the ultrasound examination proved insufficiently reliable. PMID- 1861765 TI - [Opinion of primiparae on the possibility of sex selection]. AB - Recent medical-technological developments such as chorionic villi sampling and in vitro fertilization make sex selection in principle possible. The literature and our own experiences suggest an increasing demand for it. We interviewed a selected group of 180 women regarding sex selection, of whom 127 responded. More than 80% of these rejected a selection based on sex. The legitimacy of withholding information about the sex of the foetus is questionable. The existence of a demand, however small, should prompt professionals to take a stand about its acceptability. PMID- 1861766 TI - [A patient with a wide aorta and 2 wide kidney pelves: retroperitoneal fibrosis]. AB - The case is discussed of a patient with renal insufficiency due to severe stenosis of both ureters brought about by a periaortic inflammatory process. Such periaortitis is seen in severe atherosclerosis; the condition allegedly occurs in 5 to 23% of all patients with an abdominal aortic aneurysm. The literature on this form of retroperitoneal fibrosis is reviewed. PMID- 1861768 TI - [Eurothemes. The art of diminishing the need for hospital beds: minimal art and (or) minimally invasive therapy?]. PMID- 1861767 TI - [Respiratory insufficiency and the post-polio syndrome]. PMID- 1861769 TI - [Respiratory stimulants]. PMID- 1861770 TI - [Treatment with monoclonal anti-endotoxin antibodies of patients with sepsis caused by Gram-negative bacteria]. PMID- 1861771 TI - Apical dendritic depolarizations and field interactions evoked by stimulation of afferent inputs to rat hippocampal CA1 pyramidal cells. AB - The relationship between orthodromic extracellular field potentials and intradendritic depolarizations in apical dendrites of CA1 pyramidal neurons was investigated using the in vitro slice preparation of rat hippocampus. Orthodromic synaptic field potentials evoked by stimulation of afferent inputs in stratum radiatum or stratum oriens were used to measure extracellular voltage gradients generated over the pyramidal cell axis. Extracellular gradients were of opposite polarity over the region of pyramidal cell apical dendrites in stratum radiatum. The stratum radiatum-evoked gradient was negative towards the apical dendrites and the stratum oriens-evoked gradient negative towards the cell body layer, with gradients reaching values of up to 50 mV/mm over the apical dendritic axis. Intradendritic recordings obtained greater than 150 microns from stratum pyramidale directly measured the subthreshold apical dendritic excitatory postsynaptic potentials evoked by stratum radiatum or stratum oriens stimulation. These ground-referenced recordings were then compared to the transmembrane potential calculated by subtraction of the corresponding extradendritic field potential. Both stratum radiatum and stratum oriens stimulation evoked graded excitatory postsynaptic potentials that could be recorded in apical dendritic impalements up to 265 microns from stratum pyramidale. The calculated transmembrane potential of the stratum radiatum-evoked excitatory postsynaptic potential had a significantly greater rate of rise, peak amplitude, and rate of decay than that of the ground-referenced excitatory postsynaptic potential. In contrast, the rates of rise and decay of the transmembrane potential of the stratum oriens-evoked excitatory postsynaptic potential were reduced with respect to the ground-referenced recording. The peak amplitude of the stratum oriens evoked transmembrane potential, however, varied according to the polarity of the corresponding extradendritic population spike response recorded in stratum radiatum. These data reveal that synaptic activation of either basal or apical dendrites of CA1 pyramidal cells evokes a depolarization that can be recorded over a substantial region of the apical dendritic arbor. Furthermore, extradendritic field potentials evoked by stimulation of these inputs produce opposite effects on the transmembrane potential of apical dendrites. The magnitude of the accompanying extracellular voltage gradients suggest that these shifts in transmembrane potential reflect ephaptic interactions at the apical dendritic level of pyramidal cells. PMID- 1861772 TI - The effects of caffeine on ischemic neuronal injury as determined by magnetic resonance imaging and histopathology. AB - The effects of caffeine on ischemic neuronal injury were determined in rats subjected to forebrain ischemia induced by bilateral carotid occlusion and controlled hypotension (50 mmHg for 10 min). High resolution (100 microns) multi slice, multi-echo magnetic resonance images were obtained daily for three consecutive days post-operatively in sham-operated rats and in rats that received either saline vehicle (controls), a single i.v. injection of 10 mg/kg caffeine 30 min prior to an ischemic insult (acute caffeine group), or up to 90 mg/kg per day of caffeine for three consecutive weeks prior to an ischemic insult (chronic caffeine group). Rats in the control group exhibited enhanced magnetic resonance image intensity in the striatum 24 h after ischemia which increased in the striatum and also appeared in the hippocampus after 48 h, and which began to resolve in both regions by 72 h post-ischemia. Histopathological analysis of each rat following the final magnetic resonance examination showed that ischemic neuronal injury was strictly confined to the brain regions showing magnetic resonance image changes. Acute caffeine rats showed accelerated changes in the magnetic resonance images, with increased hippocampal intensity appearing at 24 h post-ischemia. Although there was magnetic resonance evidence of accelerated injury, quantitative analysis of the histopathological data at 72 h showed no significant difference in the extent of neuronal injury in any brain region between control-ischemic and acute caffeine rats. Nine out of 11 rats in the chronic caffeine group showed no magnetic resonance image changes over the three study days. Chronic caffeine rats had significantly less neuronal damage in all vulnerable brain regions than either of the other groups of ischemic rats. The accelerated ischemic injury in rats treated with an acute dose of caffeine may occur secondary to antagonism of adenosine receptors, whereas protection from ischemic injury following chronic administration of caffeine may be mediated by up-regulation of adenosine receptors. PMID- 1861773 TI - Specific role of N-acetyl-aspartyl-glutamate in the in vivo regulation of dopamine release from dendrites and nerve terminals of nigrostriatal dopaminergic neurons in the cat. AB - Levels of N-acetyl-aspartyl-glutamate measured by high-pressure liquid chromatography were found to be very high in the cat substantia nigra, particularly in the pars compacta, while those in the caudate nucleus were much lower. In halothane-anaesthetized cats implanted with push-pull cannulae, N acetyl-aspartyl-glutamate (10(-8) M) induced a marked and prolonged release of newly synthesized [3H]dopamine, when infused into the posterior but not into the anterior part of the caudate nucleus. In contrast, in the presence of tetrodotoxin (10(-6) M), N-acetyl-aspartyl-glutamate (10(-8) M) reduced the residual release of [3H]dopamine; this effect was also more pronounced in the posterior than in the anterior part. In the conditions used, as indicated by experiments with [3H]N-acetyl-aspartyl-glutamate no glutamate was formed from the infused N-acetyl-aspartyl-glutamate. Ibotenate (10(-5) M) induced changes in [3H]dopamine release in both the absence and presence of tetrodotoxin, which were closely similar to those observed with N-acetyl-aspartyl-glutamate. Responses induced by either N-acetyl-aspartyl-glutamate or ibotenate were not mediated by N methyl-D-aspartate receptors since N-methyl-D-aspartate stimulated the release of [3H]dopamine only when used in a high concentration (10(-4) M) and applied in a magnesium-free superfusion medium in both the presence of glycine (10(-6) M) and strychnine (10(-6) M). In addition, the stimulatory effect of N-methyl-D aspartate persisted in the presence of tetrodotoxin; it was of similar amplitude in both parts of the caudate nucleus and of shorter duration than that evoked by either N-acetyl-aspartyl-glutamate or ibotenate alone. N-Acetyl-aspartyl glutamate interacted with dopaminergic neurons not only presynaptically in the caudate nucleus but also in the substantia nigra since a marked increase in [3H]dopamine release was observed both from local dendrites and from nerve terminals in the ipsilateral caudate nucleus when N-acetyl-aspartyl-glutamate (10(-7) M) was infused locally into the substantia nigra pars compacta. No effect could be seen in contralateral structures. The isomer of natural N-acetyl aspartyl-glutamate, beta-N-acetyl-aspartyl-glutamate (10(-7) M), had no effect on [3H]dopamine release when applied similarly in the substantia nigra, thus confirming the specificity of the action of N-acetyl-aspartyl-glutamate. PMID- 1861774 TI - Mapping of phenytoin-inducible cytochrome P450 immunoreactivity in the mouse central nervous system. AB - The distribution of phenytoin-inducible cytochrome P450 in non-treated mouse brain and spinal cord was analysed immunohistochemically using polyclonal antibodies against phenytoin-induced mouse cerebral microsomal P450. This P450 protein was proved in Ouchterlony [Volk B. et al. (1988) Neurosci. Lett. 84, 219 224], Western blot, and immunohistochemical analyses to be reactive to the specific antibodies and an IgG fraction raised against phenobarbital-induced rat liver microsomal P450IIB1. The phenytoin-induced P450 is designated P450IIB1* because immunologically it is comparable with P450IIB1; however, it has not yet been analysed for other characteristics of this enzyme. Immunocytochemistry was performed on acetone-fixed serial cryosections of the whole brain using the avidin-biotin-peroxidase detection system. Negative controls included incubations with preimmune serum of the immunized animal instead of the primary antibody and preabsorption of the antibody with the corresponding immunogen. The pattern of immunoreactive sites indicates that P450IIB1* is not distributed evenly throughout the CNS. It was found to be restricted to only some cellular populations. The most striking aspect of immunostaining was a predominant reactivity in the evolutionary old brain parts. Neuropil and neuronal staining was found in the spinal cord (motor neurons of the ventral horn), medulla oblongata (hypoglossal nuclei, magnocellular part of the lateral reticular nuclei), pons (trigeminal, facial, cochlear and pontine nuclei), cerebellum (granule cells), midbrain (dorsal raphe nucleus) and limbic lobe (hippocampal pyramidal cells). Neuropil reactivity alone appeared in cerebellar nuclei, midbrain, thalamus, basal ganglia, neopallium and olfactory brain. Generally, pia mater/arachnoid, ependyma, choroid plexus, vascular system and some astrocytic populations were found to be strongly P450IIB1* immunoreactive. In comparison with astroglia, which is characterized by glial fibrillary acidic protein positiveness, the astrocytes, which are also P450IIB1* reactive, occurred only in subpial and subependymal layers, and in large fiber tracts of the spinal cord and brainstem, where they were attached to the vascular system. Otherwise, the glial fibrillary acidic protein-positive astrocytes were not P450IIB1* immunoreactive in the cerebellar molecular layer (fibers of Bergmann glia), in remaining neuropils and in white matter areas. PMID- 1861775 TI - Tenotomy delays both synapse elimination and myogenesis in rat lateral gastrocnemius. AB - To investigate a possible relationship between synapse elimination and myogenesis, we examined both phenomena during the first 2 weeks of postnatal life in the rat lateral gastrocnemius muscle. Synapse elimination and myogenesis occur simultaneously. Sixty per cent of the number of fibers observed in adult muscles is generated during the first 10 days of postnatal life; during this time, the majority of muscle cells in lateral gastrocnemius also become singly innervated. We delayed synapse elimination by cutting the tendon of insertion of lateral gastrocnemius (tenotomy) on the day of birth. Both synapse elimination and postnatal myogenesis were slowed by tenotomy. Tenotomized muscles contained fewer detectable cells than unoperated contralateral control muscles. These results suggest that synapse elimination may be altered by altering postnatal muscle fiber addition. PMID- 1861776 TI - Quantitative aspects of transduction in an electroreceptor organ studied by means of experimental manipulation of the interspike interval. AB - The interspike interval histogram of spontaneously firing electroreceptor organs of freshwater catfish (Ictalurus nebulosus LeS.) fits well with the probability density function of a gamma distribution. The shape parameter r of this probability density function can be used as a measure for the firing threshold of the spike generator, and the scale parameter lambda provides a measure for the input rate of synaptic quanta. Here, we have studied the physiological meaning of the two parameters of the fitted gamma probability density function by manipulating the mean firing rate. This was done in two ways: "frequency clamp" stimulation and a change in temperature. Frequency clamp stimulation, compensating for adaptation of the response, keeps the afferent firing rate at a fixed value for a limited period. We show that within such a period not only the mean spike rate remains constant, but these spike trains can be regarded as renewal series: the spike generator is functionally uncoupled from the frequency dependent parts of the transduction path. Concerning the gamma parameters, two types of responses are found: at strong excitation lambda increases, r does not change; with small stimuli r is inversely proportional to the stimulus strength, lambda remains unchanged. This is difficult to explain when stimulus transduction acts via the synaptic input rate only. Stimulation seems to influence the firing threshold of the spike generator directly. At strong inhibition a regular firing pattern suddenly takes over; the major part of the variability suddenly disappears from the spike train. A change in temperature causes a shift in lambda (Q10 approximately 2.3), but not in r. This points to a temperature effect on the input rate only. PMID- 1861777 TI - Catecholamine synthesis inhibitors increase pineal adrenaline content by stimulating adrenal medullary activity. AB - Estimation of noradrenaline and adrenaline utilization in the pineal gland of female rats was attempted using inhibitors of the enzymes that catalyse the catecholamine biosynthetic pathway. Treatment with FLA63, an inhibitor of dopamine beta-hydroxylase (10 mg/kg, 2 h before killing), induced depletion of noradrenaline and adrenaline in the preoptic area and median eminence (sites, respectively, inside and outside the blood-brain barrier) but, paradoxically, resulted in a significant increase (+77%) in the pineal content of adrenaline without affecting that of noradrenaline. Treatment with LY134046, an inhibitor of phenylethanolamine N-methyltransferase (40 mg/kg, 5 and 2 h before killing), induced depletion of adrenaline in the preoptic area and median eminence but, again, resulted in a paradoxical and large increase in pineal adrenaline (+224%); this increase was prevented by prior adrenalectomy. Blood samples taken from free moving rats fitted with intravenous and intraperitoneal cannulae revealed a marked increase in plasma levels of adrenaline after each injection of LY134046. These results suggest that the adrenal medulla is the primary source for the increase in pineal adrenaline seen after administration of the enzyme inhibitors. The precise site of uptake and the biological implications of this phenomenon remain to be elucidated. Nevertheless, interpretation of in vivo experiments involving these catecholamine synthesis inhibitors should take this adrenal response into account. PMID- 1861779 TI - Problems mean trouble; decisions mean choices. PMID- 1861780 TI - Decision making in today's complex environment. PMID- 1861778 TI - Methodological issues in the study of divergent views of the family. AB - A wealth of methodologies, both qualitative and quantitative, are available for conducting research on divergent views in the family. While the pathways for investigating divergent views of the family are clearer for those who chose more quantitative methods (as current literature reflects this tradition), qualitative methods may serve to clarify the process through which divergent views occur and are maintained within the family, both on an individual and on a dyadic or triadic level. In terms of the analysis of data from quantitative designs, divergent views of the family can quite easily be explored by viewing the family as a system and the individual family members as components of that system. This approach minimizes problems arising from having sampled families and included more than one family member from each. In addition, the organization of the data as family (rather than individual) records enables the researcher to directly examine divergences between family members by comparing ratings by different family members on the same construct. The issues involved in such analyses were discussed, first, in terms of the reliability of difference scores and then, in more detail, in terms of alternative regression-based models that estimate the effects of differences on a dependent variable. Although differences between variables are reputed to be (and often are) unreliable, the conditions under which these scores are likely to be reliable are the conditions found when examining divergent family views. Also, the reliability of difference variables can be treated directly. The discussion of regression models indicated the statistical equivalence (or in some instances nonequivalence) of models containing difference variables to alternative models not containing difference variables. Although algebraically equivalent, these alternative linear models provide different views of the same information. When moving from linear models to nonlinear models, however, researchers are cautioned to choose each specific model carefully since the nonlinear terms containing difference variables are actually more complex than they at first appear. The current volume speaks to the importance of variation in family members' views for the adjustment and well being of adolescents. This chapter has taken on the question of how best to look at these divergences, and how different methods and statistical techniques may yield similar or different information regarding divergent views. The diversity in research methods and analytical strategies creates a challenging task for the investigator, and the continued exploration of questions regarding the implications of divergent views in the family should enhance our knowledge of how and why views diverge, as well as what divergences mean to family members. PMID- 1861781 TI - Problem solving and decision making: who owns the problem? PMID- 1861782 TI - Ethical decisions: what we learned from Cruzan about the right to die. PMID- 1861783 TI - Improving clinical care through project management. PMID- 1861784 TI - Administration and intradisciplinary conflict within nursing. PMID- 1861785 TI - Restructuring nursing services in the Mercy Health Services Consortium. PMID- 1861786 TI - The consortium demonstration project planning. PMID- 1861787 TI - The Catherine McAuley Health System, Ann Arbor project. PMID- 1861788 TI - The St. Joseph Mercy Hospital, Pontiac project. PMID- 1861789 TI - The Marian Health Center, Sioux City project. PMID- 1861790 TI - The St. Joseph Mercy Hospital, Mason City project. PMID- 1861792 TI - Quality customer service: nursing's new challenge. PMID- 1861793 TI - The home care contribution to continuity of care. PMID- 1861791 TI - The Mercy Hospital, Port Huron project. PMID- 1861794 TI - New Joint Commission standards for 1991 require R.N. decision making. PMID- 1861795 TI - A novel approach to recruitment, retention, and advancement of minority nurses in a health care organization. PMID- 1861796 TI - Flight 232: disaster planning in action. PMID- 1861797 TI - Attributes of service-based nursing research programs useful for decision-making. PMID- 1861798 TI - AIDS classification and the military. AB - In 1985 the U.S. Department of Defense took action to establish regulations for the protection of national defense personnel against the AIDS epidemic. Since that time specific procedures have been carried out in each military unit to effectively handle soldiers infected with the AIDS virus. A unique six-stage classification system for monitoring disease progression of AIDS is currently used in military medical facilities around the world, and military medicine remains active in the fight against AIDS. PMID- 1861799 TI - Vulvovaginal candidiasis: a study of immediate vs. delayed treatment on patient comfort. AB - Vulvovaginal candidiasis is a miserable infection that affects millions of women each year. The purpose of this article's study was to investigate the effectiveness of an immediate treatment intervention for increasing the comfort level of women with vulvovaginal candidiasis. An experimental study using a sample of 20 women compared the comfort of a control group, which received routine care, to the comfort of the experimental group, which received routine care plus vaginal debridement followed by application of vaginal medication. The experimental group experienced greater relief from their symptoms post-treatment than did the control group. Implications for NP practice are presented. PMID- 1861800 TI - The treatment of mild to moderate hypertension in patients with diabetes mellitus. AB - The treatment of mild to moderate hypertension in patients with diabetes mellitus is reviewed in this article. The effect of diabetic hypertension on the heart and kidney is discussed. Treatment guidelines for diabetic hypertension are provided, based on principles derived from the pathophysiology. These principles include choosing an agent that maintains or improves lipids, potassium, insulin sensitivity, and quality of life. Individuals with diabetic hypertension should be assessed for their risk of developing coronary artery disease or nephropathy, since certain antihypertensive agents may help prevent these diseases. A simple method for selecting appropriate drugs is also presented. PMID- 1861801 TI - Using a computer database to increase efficiency in the practice setting. AB - A computerized database is an invaluable tool for planning and managing patient care. The design and function of two databases for an ambulatory cardiology setting are discussed in this article. Information about patients with hyperlipidemia and with permanent pace-makers was entered into the custom designed databases. The benefits of using computers for record keeping, such as improved organization and efficiency, are also addressed. PMID- 1861802 TI - Discussion of cervical cap omitted from article. PMID- 1861803 TI - Tuberculosis in the AIDS era: a new threat from an old disease. PMID- 1861804 TI - Atypical infections of the hand and wrist. PMID- 1861805 TI - Population characteristics of tuberculosis in an HIV/AIDS registry from an East Harlem Hospital. AB - The recent increase of tuberculosis nationally and in New York City has been attributed in part to the progression of the acquired immunodeficiency syndrome (AIDS)/human immunodeficiency syndrome (HIV) epidemic. The East Harlem/South Bronx/Bushwick sections of New York City have an especially high incidence of tuberculosis. An HIV/AIDS registry (1986-1990) consisting of 1,312 patients from a community hospital serving East Harlem was examined for population characteristics associated with documented tuberculosis in the registrants. Tuberculosis affected males more commonly than females and was observed in comparable frequency in patients with AIDS-related complex (ARC) (12.9%) and AIDS (15.0%). The proportion of cases in blacks (18.3%) was significantly greater than that in Hispanics (10.4%, chi 2 = 15.196, p = 0.0003) or whites (8.7%, chi 2 = 5.62, p = 0.0171). Among intravenous (IV) drug users, the proportion of tuberculosis cases was also significantly higher in blacks than in Hispanics. These data could be consistent with a difference in exposure to tuberculosis and/or the purported racial susceptibility of blacks to tuberculosis infection. A review of new tuberculosis cases in East Harlem also suggests that blacks are at a greater risk for developing tuberculosis than Hispanics. PMID- 1861806 TI - First year medical student experiences with being discouraged from entering medical school. AB - Three hundred and fourteen first year medical students from two consecutive classes were surveyed for their experiences with being discouraged from entering medical school. Sixty-eight percent (215) had been discouraged from becoming physicians. The sources of discouragement were varied, with 43% citing physician acquaintances and 40% friends and neighbors. Parents were the principal source of encouragement (58%) followed by friends and neighbors (47%). More students (34%) were encouraged by undergraduate professors and advisors than by their family doctor (23%), a physician relative (18%), or a physician acquaintance (31%). Discouragement centered on three broad areas: diminished financial rewards, increased financial costs, and quality of life. PMID- 1861807 TI - Abdominal mass and anasarca following treatment for lymphoma. PMID- 1861808 TI - Physicians and national health insurance: some economic factors. PMID- 1861809 TI - The memoirs of Joseph Isaac Bluestone, MD. PMID- 1861810 TI - Tuberculosis of the hand and wrist. PMID- 1861811 TI - Multiple carcinomas of the large bowel in chronic ulcerative colitis. PMID- 1861812 TI - The use of prophylactic desmopressin (DDAVP) in labor to prevent hemorrhage in a patient with Ehlers-Danlos syndrome. PMID- 1861813 TI - Crack abuse and asthma. PMID- 1861814 TI - Rural obstetric care. PMID- 1861815 TI - Impact of the Great War on the medical community. PMID- 1861816 TI - Physicians and the media. PMID- 1861817 TI - Cardiac surgery research results encourage improvements in performances. PMID- 1861818 TI - New York State WIC evaluation study. PMID- 1861819 TI - Prevalence of HIV infection among childbearing women in the United States. PMID- 1861820 TI - 1991 NERF Travelling Scholar: Ginette Rodger. PMID- 1861821 TI - Professional need seen in Aotearoa. PMID- 1861822 TI - Registered midwives on the outer. PMID- 1861823 TI - Lebanon's forgotten refugees. PMID- 1861824 TI - Preventing cot death: the role of the nurse. PMID- 1861825 TI - Courses build up cheap 'nursing' workforce. PMID- 1861826 TI - Hot water bottles burn. PMID- 1861827 TI - EC eye tests undermine OH. PMID- 1861828 TI - Acting in good faith. PMID- 1861829 TI - Vacational health. PMID- 1861830 TI - Testicular cancer--case studies. PMID- 1861831 TI - Promoting continence at work. PMID- 1861832 TI - Tort reform--British style. PMID- 1861833 TI - Of lawyers and litigation. PMID- 1861834 TI - The Sudimack agenda. New president wants OSMA "Lean and mean". PMID- 1861835 TI - Only you can make the difference. Peer review needs you. PMID- 1861836 TI - [Clinical aspects of arteriosclerotic stenosis of the left coronary artery main stem]. AB - Authors have found 37 significant (greater than 50%) or severe (greater than 75%) cases of left main stem stenosis (LMS) (3.4%, 35 male and 2 female) during 1097 consecutive selective coronarography. Retrospective analysis of the clinical data of the 35 male pts. showed severe effort or resting anginal complaints in the 2/3 of the pts., however this was not in tight connection with the degree of the LMS stenosis or the number of associated peripheral coronary stenoses respectively, similar to the ischaemic disorders of the resting ECG. In the bycicle ergometry ECG data lone the double index showed statistically significant difference between the groups of less than or equal to 2 and 3 vessel diseases connected to the severe LMS. Myocardium scintigraphy was performed out in 6 pts., all of them has given positive result. They emphasise the necessarity of urgent revascularisation against the higher risk of the intervention because of the pour results of the medical treatment. PMID- 1861837 TI - [Prospective study of cardiac autonomic neuropathy in diabetes mellitus]. AB - For assessment of clinical and prognostic values of cardiac autonomic neuropathy, 53 patients with diabetes mellitus were followed-up for five years. Parasympathetic innervation was assessed by recording heart rate variability during deep breathing, Valsalva manoeuvre and lying-to-standing while sympathetic function was evaluated by measuring postural change in systolic blood pressure. During the follow-up period 1 of 23 diabetic patients died in group without signs of cardiac autonomic neuropathy whereas 2 of 13 diabetics and 10 of 17 diabetics deceased in groups with mild and definitive signs of cardiac autonomic neuropathy, respectively. At reinvestigation, the values of tests for parasympathetic impairment worsened or did not change significantly while improvement in these tests was only exceptionally observed in 40 diabetic patients. No significant change in values of test for sympathetic function was documented during the follow-up period suggesting that parasympathetic (vagal) impairment might precede the sympathetic dysfunction during development of autonomic neuropathy in diabetic patients. No correlation was observed between changes in cardiac autonomic neuropathy and alterations in distal somatic neuropathy (assessed by measurement of motor nerve conduction velocity in peroneal nerves) during the prospective study. Definitive cardiac autonomic neuropathy--as one of the late complications of diabetes mellitus--suggests poor prognosis in diabetic patients. PMID- 1861838 TI - [Practical importance of the exact diagnosis of fetal arrhythmias]. AB - Ultrasound M-mode examinations were performed at 78 pregnant women in the second half of pregnancy during 1 year period, because of fetal dysrhythmia. Distribution of the diagnoses of the fetuses: near 40% sinus rhythm, 5.13% organic heart diseases, 48.72% supraventricular arrhythmia, 5.13% atrioventricular block, 1.28% ventricular extrasystole. In 11.54% of the cases intrauterine treatment was necessary (supraventricular tachycardia) for prevention the congestive heart failure. The transplacental treatments were as follows: in 3 cases digitalis, in 3 cases digitalis + verapamil, in 3 cases digitalis + amiodaron. In two cases (refractory to the mentioned treatments) direct intrafunicular, intravascular digitalis + amiodaron treatment was reasonable. Being the correct diagnosis of dysrhythmias possible only with ultrasound M-mode examination, all of the recognised cases have to be sent to adequate ward, where a suitable equipment is available. PMID- 1861840 TI - [Hyperparathyroidism simulating severe hypercalcemia syndrome]. AB - The case history of a 65 year old female patient has been reported here by the authors. The patient was admitted to the Intensive Therapy Unit owing to her repeated heart pain. Later she was transferred to the Department of Medicine to establish the exact diagnosis. Prepyloric ulcer and hypertension were occurred in her history. The symptoms of her preceding as well as her recent illness were: pain in epigastric field, nausea, adynamia, weakness, polyuria, significant loss of weight, somnolence and the shortened Q--T time in electrocardiogram related to hypercalcemia syndrome. The calcium value in blood proved to be at critically high level from time to time. The possibility of the secondary hypercalcemic state was excluded by sonographic examination and the elevated level of parathormone in blood established the diagnosis of the hyperparathyroidism. The surgical resection of parathyroidic adenoma yielded a complete recovery of the patient. The authors call the attention to the significance of the clinical signs in the diagnosis of the disease. PMID- 1861839 TI - [A case of retroperitoneal fibrosis associated with renal angiomyolipoma]. AB - The authors performed intraperitoneal transposition of the right ureter in a patient who suffered from dilatation of the renal cavity-system due to retroperitoneal fibrosis. One and a half year later an angiomyolipoma was eliminated from the left kidney of the patient. Describing the associated occurrence of these 2 infrequent diseases the authors deal with the problem of etiology, diagnosis and treatment. PMID- 1861842 TI - [Comment on the diagnosis of coronary disease]. PMID- 1861841 TI - [Capsaicin-induced mouse ear edema and its management]. AB - Oedema was induced in one ear of male mice of the CFLP strain with capsaicin solution (10 microliters/40 micrograms/ear). The development in time and the extent of the oedema were determined by the oedema-disk gravimetric technique. The maximum oedema was attained after 1 hour, and there was subsequently a gradual decrease. The extent of the mouse ear oedema induced in this way and measured after 60 minutes was inhibited to a statistically significant degree and in a dose-dependent manner by the antihistamine chloropyramine, the antihistamine antiserotonin cyproheptadine, the non-steroidal antiinflammatory agent pyroxicam, the prostaglandin antagonist di-4-phloretin phosphate, and the lipoxygenase inhibitor nordihydroguaiaretic acid. The method proved suitable for the detection and biologically quantitative determination of the state of desensitization induced with capsaicin. PMID- 1861844 TI - [Questions concerning geriatric medical services]. PMID- 1861843 TI - [Massage from the Hungarian Medical Association of America to Orvosi Hetilap]. PMID- 1861845 TI - [HIV-infection in childhood]. AB - HIV infection in children is mainly due to vertical transmission. It has turned into a major epidemic in some developing countries. Due to the transfer of maternal antibodies to HIV early, diagnosis in infants is difficult and costly. The disease shows considerable clinical variability. Common classification and staging systems would seem very important in order to compare epidemiological, diagnostic and therapeutic studies. Treatment with anti-retroviral agents in under clinical trial and in combination with intensive supportive measures can significantly improve both survival and quality of life for HIV positive patients. Vaccination against HIV is in its early stages but holds some promise in the long run for the prevention of HIV disease in infants and children. PMID- 1861846 TI - [The effect of soybean protein on lipids and trace elements in elderly hospitalized women]. AB - Institutionalized elderly women received 5 g/day soya supplementation for three months. After having finished the soya supplementation, serum cholesterol levels of hypercholesterolemic women decreased and serum zinc levels were lower in all examined persons, compared to the status of the initiation of dietetic intervention. PMID- 1861847 TI - [Following and using the scientific literature on a home computer with the REPRINT program system]. AB - REPRINT, running on the Commodore 64 home computer, and originally meant to manage a file containing several thousand reprints, has capabilities exceeding this simple task considerably. Bibliographic data can be entered into REPRINT through a word processor or a special input program which automatically corrects usage of capital letters. Code numbers referring to the contents of a reprint can be added to the bibliographic data. Thus, scientific information not contained in the title can also be stored. Searches can be done on code numbers or on any term in the title, authors or source. REPRINT is able to read the text of an article from a disk and automatically construct the list of references to it in the format used by the periodical which the author wants to publish it. While there is no need for any computer knowledge for its application, the speed of REPRINT seems to be satisfactory: search by a code number on 600 reprints takes 48 seconds. Five years of using REPRINT have proven its capabilities to efficiently support usage of a growing personal reprint file in different phases of the process of publication. PMID- 1861848 TI - [Incidence of osteoporosis in Heves County]. AB - The socio-economic importance of osteoporosis is in the increase. The costs of the effects of reduced working capability and treatment of fractures are estimated costs only. The authors report on 146 osteoporotic patients between 1986-89, suffering from fractures. Among the patients there is a female dominance. The number of osteoporotic fractures is in the increase in the recent years. The authors pointed out the importance of early diagnosis and prevention, to solve the great social problems caused by morbidity, reduced working capability and lower life standard. PMID- 1861850 TI - [Janos Mandarus, court physician to king Ulaszlo II]. PMID- 1861849 TI - [Prostatic cancer metastasized into the kidney and kidney cancer metastasized into the lung]. AB - In a 81-years old man synchronous triple cancers (prostate, kidney and lung) were found at autopsy. The poorly differentiated prostatic adenocarcinoma metastasized to the clear cell carcinoma of the right kidney and to its solitary lung metastasis. The "neoplasm to neoplasm" metastasis and the "metastasis in metastasis" was confirmed by immunohistochemistry. PMID- 1861851 TI - [Iron deficiency anemia during the Conquest and the age of the Arpad dynasty]. PMID- 1861852 TI - [Meeting of drug experts from eastern and western Europe. (Paris, 30 January-1 February 1991)]. PMID- 1861853 TI - [Characteristics of nosocomial pneumonia]. AB - 284 patients with pneumonia treated in non-invasive chest wards were analysed in a prospective study. Out of 284 cases 26 proved to be nosocomial pneumonias. Older age, chronic non specific lung diseases, malignancies, peptic ulcus, chronic alcoholism as risk factors for nosocomial pneumonia should be taken into consideration. The pathogen agent was clearly identified in four cases, meanwhile the pathogenity of the agents was suspected at seven patients. By distribution of all pathogens the widely known bacteria are responsible for nosocomial pneumonia were less than one third of cases (in three cases Staphylococcus aureus, in one one case E. coli and Enterobacter). The possible causes of their observation were analysed. Out of the 15 pathogens Gram-negative bacilli were found in six cases only. Authors suggest to use this observation at the rational choice of empiric treatment. PMID- 1861854 TI - [Representation of the increase of fetal biparietal and thoracic diameter on a new (14-zone) ultrasonic diagnostic table]. AB - From the somatic development of the fetus one may conclude to its functional maturity and if birth is near to its life prospects too. Thus the ultrasonographic examination of the biparietal and thorax transversal diameter reflecting the somatic development is of prognostic significance too. The authors composed a new table to increase the information value of the ultrasonographic finding, for the uniform designation of the given BPD and THD (biparietal and thorax diameter) sizes and for the better recognition of the tendencies of BPD and THD changes. A new system of symbols and representation method were elaborated for the description of standard positions. According to the gestation weeks 14-14 BPD and THD size-ranges were separated. The so called "UFD" Ultrasonographic index of the Fetal Development gives information besides the gestation time also on the BPD and THD standard position of the fetus and demonstrates illustratively the direction and rate of deviation of the standard positions from the average. The system provides the possibility of a better information to the obstetrician or consulting physician who evaluates the US finding, a uniform interpretation of the findings and serves better the clinical diagnostics. PMID- 1861855 TI - [Coronary artery anomalies studied by Doppler echocardiography in infancy and childhood--possibilities and limitations]. AB - We investigated infants with Kawasaki disease, congenital coronary artery fistulas and anomalous origin of the left coronary artery from the pulmonary trunc (Bland-White-Garland syndrome) by 2-dimensional and Doppler echocardiography. We describe the systematic approach for visualizing in detail coronary anatomy by two-dimensional echocardiography. Our results suggest that this echocardiographic technique is useful for detecting coronary anomalies and has a great rolbefore angiocardiography especially in sick babies. We recommend performing 2-dimensional echocardiography in the acute and chronic stage of Kawasaki disease for evaluating coronary arterial aneurysms. PMID- 1861856 TI - [Results of skin tests, based on pollen count, in patients allergic to summertime seasonal rhinitis]. AB - Atmospheric pollen and spore contents in Szeged were determined with Lanzoni Sampler from July to October in 1989. Late-summer pollen calendar for Szeged was produced on the basis of this pollen counting. Skin prick tests in 69 patients with late-summer seasonal allergic rhinitis were carried out on the basis of this pollen calendar. All patients were found to be sensitive to Ambrosia. 83% of the patients were sensitized to Artemisia too. 93% of the patients were found to be polysensitive. 33% of the patients were found to be sensitive to Alternaria. The continuous atmospheric pollen and spore counting are of importance for the diagnosis and therapy of late-summer seasonal allergic rhinitis. PMID- 1861857 TI - [Pathogenesis of severe vision deficiency in school-age children in Hungary]. AB - A population-based aetiological study was carried out on 6 to 14 year-old severely visually handicapped children in Hungary. Of the 547 recorded cases 491 (90%) were included in the analysis. Eleven aetiological groups were separated: isolated cataracts (16.7%), congenital abnormalities of the eye (15.1%), high myopia +/- retinal detachment and other cases (13.4%), retinopathia praematurorum (11.0%), choroidoretinal degenerations (10.0%), syndromes (9.6%), nystagmus and/or hypermetropia (9.0%), isolated and complicated optic atrophy (6.7%), postnatal causes (4.9%), retinoblastoma (1.8%), praenatal causes (1.8%). A significantly higher rate of previous induced abortions was found in the group of retinopathia praematurorum. Perinatal damage syndrome and Mendelian monogenic defects are the two most common aetiological categories in the origin of severe visual handicaps in Hungary. PMID- 1861858 TI - [Primary (B-cell) mediastinal lymphoma]. AB - The authors present two cases of a new pathological entity--primary (B-cell) mediastinal lymphoma. The disease both clinically and histologically differ from the known lymphomas. Its diagnosis is possible only with the use of immunhistochemical methods. The low age incidence, the unusual course and the bad prognosis of the disease merits its publication. PMID- 1861859 TI - C-myc and the yeast transcription factor PHO4 share a common CACGTG-binding motif. AB - The basic-helix-loop-helix (b-HLH) motif is common to a number of proteins involved in transcriptional regulation and cell-type determination. The b-HLH motif is also present in the S. cerevisiae transcription factor PHO4 which positively regulates the acid phosphatase gene PHO5. In this report we show that the b-HLH region of PHO4 is sufficient to confer specific DNA-binding to the sequence CACGTG and, by comparison of the basic regions of PHO4 with those of other recently isolated CACGTG-binding proteins, we identify a specific subset of conserved amino acids in the basic region likely to confer DNA-binding specificity. On the basis of these observations we predict successfully the effect of substituting the PHO4 basic region with that from c-myc and show that the chimaeric protein activates transcription from the CACGTG elements present in the PHO5 UAS. From these data it is clear that the myc basic region confers specific binding to the sequence CACGTG. PMID- 1861860 TI - Failure of senescent cells to phosphorylate the RB protein. AB - The product of the RB susceptibility gene has been shown to be differentially phosphorylated during the cell cycle, suggesting a role in the regulation of cell cycle progression. We examined the expression and phosphorylation status of the RB protein in senescent Syrian hamster embryo cells. Both phosphorylated and unphosphorylated forms of the RB protein were observed in cells at early passages; however, only unphosphorylated RB protein was found in senescent cells. When nonsenescent cells at low population doubling levels were made quiescent by reducing the serum concentration of the media, the RB protein in these cells was mostly in the unphosphorylated form. When stimulated with serum, phosphorylation of the RB protein occurred between 10-20 h after stimulation, which corresponded with the induction of DNA synthesis. Senescent cells, in contrast, did not show any phosphorylation of the RB protein in response to serum. In addition, cell lines that had escaped cellular senescence at various stages of neoplastic progression were examined; all 25 cell lines examined expressed RB protein, which was phosphorylated normally. These results suggest that the RB protein plays a role in cellular senescence with phosphorylation status determining this role. Factors controlling this phosphorylation are potential key factors in controlling cellular life span in culture. PMID- 1861861 TI - Effects of MGSA/GRO alpha on melanocyte transformation. AB - In the work described here we demonstrate that the clonal cell line Mel-a-6, produced by transfection of mouse Melan-a cells with human MGSA, had an increased ability to form large colonies in soft agar and increased ability to form tumors when injected into nude mice as compared to cells transfected with the neomycin resistance gene alone. This effect appeared to be dependent on the levels of MGSA produced since another transfected clone, Mel-a-l, produced only a low level of MGSA transgene mRNA, formed only minimal large colonies in soft agar and had a tumorigenic rate equal to that of neomycin resistant controls. The histology of the Mel-a-6 tumors is compatible with features normally exhibited by melanoma tumors. The cells do not stain for melanin, and they are positive for the neural crest marker protein S-100 as well as the HMB 45 melanoma specific antigen. Immunohistochemical studies revealed expression of the human MGSA in tumor cells from tissues, excised from animals injected with cells from clone Mel-a-6. Whereas DNA ploidy analysis suggests that in vitro the Mel-a parent cell line, control Mel-a-neo, Mel-a-1 and Mel-a-6 cells show no evidence of aneuploidy, the nuclei isolated from the tumors from animals injected with Mel-a-6 do exhibit aneuploidy. These data suggest that over-expression of MGSA in immortalized melanocytes contributes to transformation. PMID- 1861862 TI - Constitutive overexpression of a 89 kDa heat shock protein gene in the HBL100 human mammary cell line converted to a tumorigenic phenotype by the EJ/T24 Harvey ras oncogene. AB - The non tumorigenic human mammary cell line HBL100 has been transformed by the EJ/T24 human bladder carcinoma Harvey(Ha)-ras oncogene. Six cell lines were established from transformed colonies. They all expressed a high level of the ras oncogene and were tumorigenic in athymic nude mice. During an in vivo passage in animals, tumour cells presenting a growth advantage were selected, and some of the tumours revealed an amplification of the transfected ras sequences. Using this model of human cell transformation, we have isolated a cDNA clone corresponding to a heat shock protein gene (hsp89 alpha). This gene, normally transcribed at a higher rate in response to serum stimulation, was found to be constitutively overexpressed in ras-transformed HBL100 cells. In contrast, a closely related hsp gene (hsp89 beta), remained sensitive to serum stimulation, in both untransformed and ras-transformed HBL100 cells. Thus, the regulation of the expression of the hsp89 genes, upon serum stimulation, involves ras-dependent and ras-independent pathways. Constitutive overexpression of the murine homolog of the hsp89 alpha was observed in NIH3T3 cells transformed by the three ras oncogenes, but not with some other oncogenes. Therefore, alteration of the hsp89 alpha gene expression is not a general characteristic of transformed cells, but seems to be linked to ras transformation. PMID- 1861864 TI - Loss of heterozygosity for chromosome region 11p15 in Wilms' tumours is not related to HRAS gene transforming mutations. AB - Although a candidate Wilms' tumour gene--WT1--has been identified in chromosome region 11p13, there is strong evidence from loss of heterozygosity studies suggesting that a second relevant gene is present in region 11p15. The Harvey-Ras proto-oncogene also lies in this region. In other types of tumours mutations in RAS genes have been associated with the development and/or progression of a number of tumour types. We therefore analysed the sequence of the Ras oncogene for possible mutations in six Wilms' tumours showing loss of heterozygosity for chromosome region 11p15. No tumour analysed showed HRAS sequence mutations. We conclude that loss of heterozygosity at 11p15 does not implicate HRAS mutations in the molecular pathogenesis of Wilms' tumour. PMID- 1861863 TI - Lack of nuclear RB protein staining in G0/middle G1 cells: correlation to changes in total RB protein level. AB - Functional loss of the retinoblastoma (RB) gene has been implicated in a diverse group of human malignancies. The potential clinical importance of such loss demands a reproducible RB cell staining method to distinguish RB+ from RB- tumors. We report that normal and known RB+ tumor cells either in culture or in vivo display a mosaic RB staining pattern with variable proportions of cells having unstained nuclei which are indistinguishable from truly RB- tumor cells. We also show that the apparent lack of nuclear staining corresponds to RB+ cells which are in the G0 or middle G1 phase, where as much as 10-fold decrease in total cellular RB protein occurs compared to their G2/M phase counterparts. These findings not only provide new clues to RB protein function in cell growth and differentiation, but also need to be considered when evaluating the RB status in primary malignancies for its role in tumor initiation/progression or as a prognostic parameter. PMID- 1861866 TI - Predicted tyk2 protein contains two tandem protein kinase domains. AB - Tyk2 was recently described as an 1187 amino acid protein with a putative protein tyrosine kinase domain near its C-terminus and no similarity to other proteins in the approximately 900 amino acids preceding the kinase domain. I report here, however, that tyk2 contains an additional protein kinase domain, and that the two tandem kinase domains are preceded by an SH2-like, putative regulatory domain. PMID- 1861865 TI - Membrane-anchored forms of EGF stimulate focus formation and intercellular communication. AB - Epidermal growth factor (EGF) is the prototype for a small family of soluble proteins that bind to and activate the EGF receptor. These proteins are derived from larger propeptides that are anchored to the plasma membrane. Although the signalling properties of soluble EGF are well-characterized, the signalling potential of the membrane-anchored form had not been determined. We therefore investigated whether membrane-anchored EGF can stimulate the EGF receptor. An EGF mini-gene expression system that we had previously constructed for expression of soluble EGF was modified to encode anchored forms of EGF. In the encoded proteins EGF was fused to the spacer in the EGF propeptide that separates EGF from the transmembrane domain. The spacer was followed by vesicular stomatitis virus G protein transmembrane and cytoplasmic domain sequences. Three forms of EGF/G fusion protein were expressed in rat fibroblasts. The plasmids for expression of anchored EGF induced focus formation in rat fibroblasts, indicating that anchored EGF can cause autocrine transformation. When mixed with indicator HeLa cells, cell lines expressing EGF/G fusion proteins activated the HeLa EGF receptor. This activation was mediated by cell-associated, rather than soluble EGF. The finding that membrane-anchored EGF is capable of activating the EGF receptor on neighboring cells has broad implications for the functions of EGF in the organism. PMID- 1861867 TI - Altered post-translational processing of p21ras oncoprotein in a transformation suppressed cell line. AB - We have isolated a transformation-suppressed cell line, R35, which is altered in the maturation of p21ras. It was obtained from the transformed cell line NIH3T3(rasEJ) as a revertant with flat morphology and anchorage dependent growth. Immunoprecipitation of steady state labeled ras proteins reveals that the revertant produces p21ras, and in addition, accumulates a protein that migrates as 23kD. Fusion of revertant cells with nontransformed rat2 cells yields cell hybrids which are retransformed and do not accumulate p23, suggesting that accumulation of p23 and suppression of transformation may be related. The accumulated p23 appears to be a precursor to p21 because (1) pulse labeling and cell fractionation of revertant cells shows that label chases from cytoplasmic p23 to membrane-associated p21, although at a slower rate, and (2) the p23 of revertant cells is indistinguishable from the p23 precursor of p21 in parent cells by partial V8 protease digestion and two dimensional electrophoresis. R35 cells are slower than their transformed parent in palmitylation and polyisoprenylation, but not in methylation of ras proteins. These results suggest that the transformation-suppressed cell line R35 is defective in the rate at which it posttranslationally processes ras proteins, possibly because it is slower in polyisoprenylation of the cytoplasmic p23 precursor protein. PMID- 1861868 TI - The stimulation of quiescent rat fibroblasts by v-src and v-fps oncogenic protein tyrosine kinases leads to the induction of a subset of immediate early genes. AB - The stimulation of quiescent murine fibroblasts by growth factors and by phorbol esters results in a rapid and transient transcriptional activation of a large group of so-called immediate early genes. Several such genes were found to be induced in chicken embryo fibroblasts following activation of a temperature sensitive (ts) Rous sarcoma virus v-src mutant following temperature shift (Simmons et al., 1989). In contrast, the classical immediate early genes c-myc, c fos and c-jun were essentially uninducible upon activation of a ts v-src mutant in rat-1 fibroblasts (Welham et al., 1990). We have cloned 9 cDNAs of genes that are rapidly and transiently inducible in rat fibroblasts by ts v-src mutants, and by a ts Fujinami sarcoma virus v-fps mutant. Six of these cDNAs are derived from the known immediate early genes NGFI-A, KC, c-fos, tissue factor, PC4 and ornithine decarboxylase; the other three cDNAs have not been described before. These 9 genes showed individual profiles of inducibility by fetal calf serum, epidermal growth factor (EGF) and by phorbol esters. Their response to the retroviral oncogenic protein-tyrosine kinases correlated best with the one to EGF, suggesting a common pathway of signal transduction. c-fos did not respond strongly to this pathway but was well induced by fetal calf serum. NGFI-A, however, was induced to a similar extent by all activators tested. Furthermore, we demonstrated that the induction of several of these genes by the retroviral oncogenic protein-tyrosine kinases is rapid, direct and occurs at the transcriptional level. PMID- 1861870 TI - A corrected sequence for the predicted protein from the mitogen-inducible TIS11 primary response gene. AB - We previously reported the sequence of a cDNA, TIS11, cloned from TPA-treated Swiss 3T3 cells. Two laboratories have reported sequences for cDNAs that have a region of identity with the TIS11 cDNA, but differ in their 5' and 3' flanking regions. We now report that the original TIS11 cDNA is likely to be a chimeric molecule, and find that the TIS11 gene encodes a protein identical to the TTP and Nup475 genes. PMID- 1861869 TI - N-myc oncogene enhances mitogenic responsiveness of diploid human fibroblasts to growth factors but fails to immortalize. AB - The N-myc gene is amplified in several types of human tumors. To assess the role of the N-myc gene in the transformation of normal human cells, we transfected an N-myc expression vector into diploid human fibroblasts. Transfected clones were isolated and found to express the N-myc gene at levels similar to those seen in a tumor cell line (neuroblastoma LA-N-1) which contains an amplified N-myc gene. The level of N-myc expression decreased as the N-myc clones senesced. Clones expressing N-myc had an increased saturation density and an altered morphology but did not have an extended lifespan. Under low serum conditions, neither the clones expressing N-myc nor the control cells showed anchorage-dependent growth. Clones expressing N-myc were compared to control cells to determine if different growth factors would affect the ability of cells to grow in soft agarose. Clones expressing N-myc and the control cells did not grow in soft agarose supplemented with epidermal growth factor (EGF) or transforming growth factor-alpha (TGF alpha). However, compared to control cells, clones expressing N-myc grew in agarose 2.8- to 18-fold higher in response to basic fibroblast growth factor (bFGF) and 5.5- to 55-fold higher in response to platelet-derived growth factor B chain homodimer (PDGF-BB). PMID- 1861871 TI - The gene from the short arm of chromosome 3, at D3F15S2, frequently deleted in renal cell carcinoma, encodes acylpeptide hydrolase. AB - Loss or inactivation of a gene on the short arm of chromosome 3 may contribute to the genesis of renal cell carcinoma. A gene that corresponds to the most frequently lost RFLP site (D3F15S2) is expressed in a variety of human tissues, and at a particularly high level in the kidney. Its expression is markedly reduced in renal cell carcinoma. A database search showed that the gene product is closely related to or identical with acylpeptide hydrolase. The nucleotide identity between the rat acylpeptide hydrolase and the human gene at D3F15S2 is 88%, compatible with normal species differences. It is therefore likely that the human gene product is acylpeptide hydrolase. The renal cell carcinoma is then associated with a decrease of acylpeptide hydrolase activity. The gene may represent a tumor suppressor gene, whose loss contributes to the development of renal cell carcinoma. It might be speculated that it could act e.g. by affecting the activity of a small acetylated growth factor. Alternatively, its decreased expression may merely reflect the impairment of differentiation in RCC, compared to normal kidney. Loss of a linked but irrelevant gene by the 3p deletion is another possibility. PMID- 1861873 TI - Simultaneous interview technique for patients with persistent pain. PMID- 1861872 TI - Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial. AB - Although amitriptyline relieves pain in many patients with painful diabetic neuropathy, side effects often preclude effective treatment. Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressants. We compared a 6 week course of desipramine (mean dose, 201 mg/day) to active placebo in 20 patients with painful diabetic neuropathy in a double-blind crossover trial. Pain relief with desipramine was statistically significant in weeks 5 and 6. Eleven patients reported at least moderate relief with desipramine, compared to 2 with placebo. Pain relief tended to be greater in depressed patients, but relief was also observed in patients who did not show an antidepressant effect. We conclude that desipramine relieves pain in many patients with painful diabetic neuropathy, offering an alternative for patients unable to tolerate amitriptyline. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressants proven effective in neuropathic pain, may mediate this analgesic effect. PMID- 1861874 TI - What is the definition of breakthrough pain? PMID- 1861875 TI - Jaw pain and tenderness levels during and after repeated sustained maximum voluntary protrusion. AB - Eight normal male volunteers performed 4 repeated sustained voluntary isometric protrusive jaw muscle contractions of 25, 50, 75 and 100% of maximum effort. Each contraction was sustained until maximum pain tolerance was reached, and all 4 contractions were completed within a single 120-min experimental period. A 30-min rest period followed each sustained contraction. The following measurements were made before and 1, 2, 3, and 7 days after the experiment: (1) superficial masseter and anterior temporalis muscle pain threshold; (2) maximum active pain free jaw opening and lateral excursion; and (3) current overall jaw pain level. None of these measurements showed any significant post-experimental changes. Contrary to common clinical belief, these results suggest that in healthy male subjects, significant jaw pain and tenderness following repeated sustained isometric protrusion efforts are difficult to induce. PMID- 1861876 TI - Comprehensive multidisciplinary treatment of chronic pain: a follow-up study of treated and non-treated groups. AB - There are relatively few outcome studies of multidisciplinary chronic pain programs which have utilized no-treatment comparison groups. The present study compared a group of chronic pain patients (N = 42) treated in a comprehensive multidisciplinary pain program with a group of patients (N = 15) who were evaluated but not treated. Comparisons were made at evaluation and at a follow-up period averaging 11 months later. From evaluation to discharge, the treated group showed significant increases in physical functioning. From evaluation to long term follow-up, both the treated and non-treated groups showed significant decreases in self-report pain ratings and interference with activities ratings. However, only the treated group showed a significant decrease in addictive medication use and increase in work functioning. The return-to-work rate for the treated group was 48% with an additional 28% of the patients being returned to vocational rehabilitation. None of the non-treated group returned to work or vocational rehabilitation. Results are discussed in terms of their support for the conclusion that comprehensive multidisciplinary pain programs produce marked subjective and functional changes. PMID- 1861877 TI - Pain causes in 200 patients referred to a multidisciplinary cancer pain clinic. AB - Causes of pain were analysed in 200 patients referred to a specialized cancer pain clinic. Pain caused by tumour growth was found in 158 patients, pain secondary to cancer or its treatment in 116 patients and pain unrelated to cancer in 33 patients. Visceral involvement (74 cases), bone metastases (68 cases), soft tissue invasion (56 cases) and nerve/plexus pressure or infiltration (39 cases) were the most frequent causes of pain due to tumour growth. Myogenic pain (68 cases) was the most frequent cause of secondary pain. The patients presented with a multitude of different combinations of causes of pain, the majority having at least two separate causes. Since pain treatment in cancer patients should be determined by its aetiology, a detailed analysis of the pain condition in each patient should form the basis for a rational therapy. PMID- 1861878 TI - Deep brain stimulation: a review of basic research and clinical studies. AB - Deep brain stimulation for pain control in humans was first used almost 30 years ago and has continued to receive considerable attention. Despite the large number of clinical reports describing pain relief, numerous studies have indicated that the results of these procedures vary considerably. In addition, many neurosurgeons find the procedures unpredictable, and considerable disagreement still exists regarding important issues related to the technique itself. This review gives an historical overview of the relevant basic and clinical literature and provides a critical examination of the clinical efficacy, choice of stimulation sites, parameters of stimulation, and effects on experimental pain. Finally, we give suggestions for future research that could more definitively determine the usefulness of deep brain stimulation for pain control. PMID- 1861879 TI - Thermographic observations on rats with experimental neuropathic pain. AB - Infrared thermographic images were obtained from the plantar hind paws of rats with an experimental nerve injury that produces signs of neuropathic pain. Thermograms confirmed that the experimental neuropathy produces signs resembling those of patients with neuropathic pain. The hind paws on the nerve-damaged side were abnormally hot, abnormally cold, or apparently normal 8-16 days post injury, a variability that is seen clinically in neuropathic pain patients. Abnormally cold hind paws became warm as soon as the injured sciatic nerve was transected, indicating that the underlying vasoconstriction was mediated by neural impulse activity. Xylazine (Rompun), a sympatho-inhibitory alpha 2-adrenoceptor agonist that normally increases cutaneous temperature, caused the hind paw on the control side to warm, as anticipated, while causing paradoxical cooling of abnormally hot hind paws, and even of 'normal temperature' paws on the nerve-injured side. These findings shed light on possible mechanisms underlying abnormal deviations of skin temperature as a symptom of nerve injury. The findings also attest to the usefulness of the experimental animal model of neuropathic pain and of the thermographic method. PMID- 1861881 TI - Evidence for a central but not a peripheral analgesic effect of clomipramine in rats. AB - The effect of clomipramine (CMI), a tricyclic antidepressant, was studied on an acute inflammatory pain model in an attempt to understand its potential antinociceptive activity, the involvement of a central and/or peripheral component and its influence on the inflammatory process. When administered (i.v.) before the inflammatory agent, carrageenan (CAR), CMI (0.125, 0.25 and 0.5 mg/kg) completely prevented the development of the hyperalgesia for 70-120 min according to the doses. This antinociceptive effect was suppressed by naloxone (100 micrograms/kg i.v.) for 65 min. Neither higher doses (1, 2 and 20 mg/kg, i.v.) nor CMI injected into the inflamed paw (15 min before CAR) modified pain thresholds. Moreover, CMI (0.5 and 2 mg/kg, i.v.) administered 15 min before CAR markedly increased the volume of the CAR-induced oedema. These results (1) demonstrate an opioid-dependent antinociceptive effect of CMI on this model, the doses used being lower than those active in thermal or electrical tests, and (2) tend to exclude a peripheral mechanism and an NSAID-like anti-inflammatory activity suggested by previous in vitro studies. PMID- 1861880 TI - Receptive properties of pial afferents. AB - The blood vessels and the pial surface of the brain, spinal cord and its roots are innervated by primary afferent neurones. Here, we have electrophysiologically characterized the functional properties of a subpopulation of these afferent fibres that supply the ventral roots of the cat sacral spinal cord. We have taken advantage of the unique anatomical arrangement of these primary afferent neurones which have their central axon in the dorsal root and project with their peripheral process into the segmental ventral root. In 10 experiments, 14 units were recorded in the dorsal root S2 which responded to electrical stimulation of the segmental ventral root. As judged by their conduction velocity ranging from 0.1 to 2.3 m/sec, all fibres were unmyelinated. In 4 cases a spot-like receptive field was located on the root where the units were reproducibly activated by mechanical stimuli, the most effective being a slight stretch. In two units tested, topical application of hypertonic saline onto the receptive field, but not at other portions of the axon elicited a long-lasting vigorous discharge with intermittent bursts. There was no obvious association of the receptive field with small blood vessels. In 5 of the 14 units including 2 with a mechanosensitive receptive field we observed latency jumps of the action potential with electrical stimulation of the ventral root close to the dorsal root ganglion. In some of these units latency jumps were also observed at other positions when the stimulation electrodes were moved centrally towards the spinal cord. We conclude that a subpopulation of unmyelinated fibres in the spinal ventral root are primary afferents innervating the root proper or its sheath.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861882 TI - Barrett's esophagus. A review of the pathologist's role in diagnosis and management. PMID- 1861883 TI - Small airways disease. PMID- 1861884 TI - The pathology of immunoblastic proliferations. Reaction, prelymphoma, lymphoma. AB - This report has attempted to review the pathology of immunoblastic proliferations, to indicate their similarities and differences, and hopefully to offer some guidelines in the approach to their diagnosis. Their pathology, immunology, and clinical features overlap, making it necessary to evaluate all possible parameters in reaching definite diagnoses. Methods to identify predominant B- or T-cell populations in order to distinguish the neoplasms from the reactive or prelymphomatous lesions can be readily employed using immunohistochemical techniques on either snap-frozen or paraffin-embedded sections. Flow cytometry can be employed to identify major cell populations and evaluate DNA ploidy. DNA probe techniques and cytogenetic evaluation further define the possible clonality of immunoblastic proliferations. Common sense is a basic index for the initial approach to the problem. The abnormal immune lesions present firm challenges in histological diagnosis and in dealing with the concepts of the disease. The immunoblastic sarcomas must be recognized for their status as high-grade lymphomas and separated from the benign reversible reactions and problematic, potentially fatal abnormal immune processes. PMID- 1861885 TI - The spontaneous regression of neuroblastoma. Experimental evidence for a natural host immunity. PMID- 1861886 TI - Folliculitis. A clinicopathologic review. PMID- 1861887 TI - AIDS meningoencephalomyelitis. Pathogenesis and changing neuropathologic findings. PMID- 1861888 TI - Pathologic changes of the cardiac conduction tissue in sudden unexpected death. A review. PMID- 1861889 TI - Fine-needle aspiration biopsy of the prostate. PMID- 1861890 TI - Sex is not just a three-letter word. PMID- 1861891 TI - Adolescent sexuality: overview and implications for the pediatrician. PMID- 1861892 TI - Adolescent sexuality: current issues. PMID- 1861893 TI - Sexually transmitted diseases in adolescents: update 1991. AB - Clinicians caring for sexually active adolescents are likely to be called on to diagnose and treat many of the STDs discussed in this article. A variety of other STDs not covered here also may be observed, including lymphogranuloma venereum, granuloma inguinale, molluscum contagiosum, scabies, pediculosis, and hepatitis A, B, and C. Some of the special issues related to gay and lesbian youth are discussed in the article by Drs Bidwell and Deisher (see "Adolescent Sexuality: Current Issues," pp 293-302). Nonetheless, it should be mentioned that the same STDs occur in homosexual youths as in their heterosexual counterparts. However, the prevalence rates for many STDs differ between the two groups, and some STDs are rarely seen in heterosexual males. These discrepancies may be explained by a number of determinants including anatomic and physiologic factors (eg, lesbian women have lower rates of STDs), differences in sexual practices (eg, genital anal and oral-anal contact), and numbers of sexual partners, although this last factor may be less important in adolescents as compared with adult gay men. Discovery of one STD should always prompt a search for others because multiple concurrent infections is the rule rather than the exception. A serologic test for syphilis and a discussion of the potential for HIV infection (possibly testing for HIV as well) should take place at each new encounter for an STD. Some patients, including those with multiple partners, have an increased chance for acquisition of an STD. However, the reality is that any adolescent who has had sexual intercourse could have an STD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861895 TI - Adolescent pregnancy. PMID- 1861894 TI - Contraceptive choices for adolescents. PMID- 1861896 TI - Children's Commission report: like sand castles in the summer. PMID- 1861897 TI - Becoming parents: feelings of adoptive mothers. AB - In a research study to determine feelings and reactions of first-time adoptive mothers, 24 adoptive mothers and 24 birth mothers were interviewed and the findings compared. Adoptive mothers react to their babies in much the same way that birth mothers do, but are often less prepared for parenting. Nurses can counsel them about the range of feelings normally experienced by both adoptive and birth mothers to allay many concerns and facilitate the process of becoming parents. PMID- 1861898 TI - Changes in parent-child relationships following divorce. AB - Divorce imposes numerous stressors that disrupt parent-child relationships at a time when they are critical in facilitating children's adjustments. Early intervention can improve outcomes for both parents and children. PMID- 1861899 TI - Children of battered women: worries about their mothers. AB - Children of battered women report a variety of worries about their mothers. In a study of 50 children (ages 10-17 years) from 5 battered women's shelters, children revealed worries about potential hazards and actual health hazards regarding their mothers. Nursing attention to worries provides information about the emotional lives of these children and helps them deal with expressed concerns. PMID- 1861900 TI - Retinopathy of prematurity: nursing interventions. AB - The exact cause(s) of retinopathy of prematurity (ROP) are not known, however, research has implicated numerous risk factors. Nursing interventions can reduce the risk regarding oxygen and light. Currently, our best nursing efforts include support and education for the family and developmental-based nursing interventions for the infant or child blinded or visually impaired by ROP. PMID- 1861901 TI - The child with an Ilizarov external fixator. AB - The Ilizarov External Fixator is gaining popularity as the most effective method to correct limb length deficiencies, correct angular deformities, and aid in the restoration of a limb compromised by traumatic injuries. Nurses caring for a child having this procedure need an understanding of the device application and appropriate nursing strategies. PMID- 1861903 TI - Vaccines. PMID- 1861902 TI - Children's compliance to dialysis. AB - Relationships among physiologic measures of compliance to dialysis therapy and selected parent and child variables were investigated. Child's age and length of time receiving dialysis related significantly to compliance. PMID- 1861904 TI - Evaluation of tympanic membrane thermometer for use with pediatric patients. AB - To determine if a tympanic membrane thermometer is of benefit on a pediatric unit. Temperature readings using a tympanic membrane thermometer and an electronic thermometer were compared for 295 paired observations. The electronic temperature readings were done by rectal (n = 32), oral (n = 65), and axillary (n = 198) routes. Differences in tympanic and electronic readings were compared by paired t-tests, and the readings were also correlated. The nursing time in seconds was also compared between electronic and tympanic measurements. Parents and nurses rated their opinion of each type of measurement on a 0-5 Likert scale. Nurses rated the patient's response using the same scale. Results indicate that temperature readings differ by an average of .2- .5 degree between tympanic and electronic thermometers. Correlations are statistically significant but of low-to moderate strength. Parents and nurses did not rate the types of instruments differently. The nurses rated the electronic axillary method as being more acceptable to toddlers. The tympanic membrane measurement took an average of 30 38 seconds less time to take. Tympanic membrane thermometry saves nursing time. Although the correlations were not strong between electronic and tympanic membrane measurements, the tympanic reading was closer to the electronic rectal reading than to axillary or oral readings. PMID- 1861905 TI - An overview of public sector financing for pediatric home care: Part 2. AB - This article is the second of a two-part series providing an overview of the public sector financing plans for children who require pediatric services at home and in the community. It is intended to assist families and health care professionals in accessing services that would alleviate some of the costs of long-term care. PMID- 1861906 TI - A community hospital-based breastfeeding counseling service. AB - Providing timely advice and support to the lactating mother is essential for successful breastfeeding. An organized breastfeeding consultation program can offer prenatal education and early postpartum intervention for lactation problems in order to decrease the possibility of early weaning. PMID- 1861907 TI - Listening: a key management tool. AB - Listening is an essential aspect of communication. It may take time to really listen to what is being said during many management meetings, however, the time saved by understanding the message the first time around and acting on the information in a quick and responsive manner is time gained by the effective listener. Hopefully, we will think twice before bringing work to another meeting. PMID- 1861908 TI - Health behavior surveys for youth. AB - In recent years, many health-related risk behavior surveys have been developed for youth. Three of these inventories - the Wellness Check Teen Health Risk Appraisal, the Adolescent Health Survey, and the Youth Risk Behavior Survey - are used widely, and pediatric nurses need to be familiar with them to enhance health promotion activities. PMID- 1861909 TI - Humor used to cope with difficult camp experience. PMID- 1861910 TI - The PNP education and certification relationship. PMID- 1861911 TI - School-based clinics: ensuring access to the health care for adolescent America. PMID- 1861912 TI - Humanism in critical care: a blueprint for change. AB - The critical care environment is often described as contrary to the humane treatment of critically ill patients and their families. To diminish the negative effects of the environment and critical illness, specific strategies to foster more humane care are needed to create an environment where healing and recovery are possible. PMID- 1861913 TI - SKIP Camp: a summer camp for special kids. PMID- 1861914 TI - Pediatric management problems. Acute bacterial sinusitis. PMID- 1861915 TI - Chronic fatigue in adolescents. AB - Nine female and 6 male adolescents (mean age 14.5 +/- 1.7 [SD] years) were evaluated for chronic fatigue associated with at least three additional symptoms present for 18.4 +/- 8.4 months. Eleven subjects experienced the onset of symptoms with an acute illness (seven Monospot-positive). Medical history, physical examination, and laboratory testing yielded little helpful information. Serologic testing for Coxsackie B viruses 1 through 6, cytomegalovirus, Epstein Barr virus, human herpesvirus 6, and Toxoplasma gondii in subjects and healthy controls provided little evidence for an infectious cause of persistent fatigue. Children's Depression Inventory scores and psychiatric interviews with the Schedule for Affective Disorders and Schizophrenia-Children's Version (K-SADS) identified five subjects with major depression. On the K-SADS, the 10 fatigued subjects without major depression endorsed many secondary symptoms of depression but were less likely than depressed psychiatric clinic patients to endorse primary symptoms such as depressed mood, guilt, and suicidality. At telephone follow-up 13 to 32 months after intake, 4 subjects were completely well, 4 markedly improved, and 7 unimproved or worse. Further research is necessary to determine whether chronic fatigue in adolescents is prodromal depression, a discrete psychosomatic condition, or an infectious or immunologic disorder that mimics depression. PMID- 1861916 TI - Pediatric heart transplantation at Stanford: results of a 15-year experience. AB - The long-term results of pediatric heart transplantation were evaluated in 53 patients, aged 0.25 to 18.94 years, who received transplants at Stanford University Medical Center between 1974 and 1989. Indications for transplantation were idiopathic cardiomyopathy (68%), congenital heart disease (21%), endocardial fibroelastosis (8%), and doxorubicin cardiomyopathy (3%). Immunosuppression was achieved with combinations of cyclosporine, prednisone, and azathioprine. Thirty seven of 42 recipients leaving the hospital after transplantation were alive and in New York Heart Association class I at study's end. Cumulative survival was 79% at 1 year, 76% at 3 years, and 69% at 5 years. Fourteen recipients have survived more than 5 years (5.1 to 12.4 years). Hospital readmission for illness has been infrequent, decreasing from 6.8 days to 0.9 days per year over 5 years. Eleven patients have required no rehospitalization. Posttransplant deaths were due to infection (19%), rejection (4%), pulmonary hypertension (4%), coronary artery disease (2%), and lymphoproliferative disease (2%). Retransplantation was required for intractable rejection in 4 patients and advanced coronary artery disease in 2. Hypertension and elevated blood urea nitrogen and creatinine levels were common in individuals receiving cyclosporine. Growth was often impaired in prepubertal children receiving daily prednisone. Based on this 15-year experience, it is concluded that heart transplantation represents a reasonable alternative for selected young patients with end-stage cardiac disease. PMID- 1861917 TI - Randomized, controlled trial comparing long-term sulfonamide therapy to ventilation tubes for otitis media with effusion. AB - Several studies have indicated that either the surgical insertion of ventilation tubes (VTs) or long-term treatment with sulfonamide-based antibacterials is effective in the management of otitis media with effusion (OME; otherwise known as serous otitis media, secretory otitis media, and glue ear) when compared with a no-treatment control or placebo. This controlled trial is the first to compare directly the effectiveness of these two treatments for long-standing OME. Outcome variables are treatment success rates, hearing thresholds, recurrent acute otitis media episodes, and side effects of medication or complications of VT placement. One hundred twenty-five children (aged 2.5 to 7 years) who met the usual indications for surgery (long-standing [greater than 3 months] OME and conductive hearing loss) were randomly assigned to "medical" treatment (sulfisoxazole 75 mg/kg per day for 6 months) or "surgical" treatment (bilateral insertion of VTs). Subjects underwent pure-tone audiometry (500, 1000, 2000, 4000 Hz) and otomicroscopic examination at 2, 4, 6, 12, and 18 months. A significantly greater proportion of medical subjects (67%) than surgical subjects (48%) were treatment failures at 6, 12, or 18 months (P = .0208). Surgical subjects had significantly better hearing at 2 and 4 months (P values less than .01) but not at 6, 12, and 18 months (P values greater than .2). A significantly greater proportion of surgical subjects (50%) experienced complications of treatment than did medical subjects (9%) (P less than .001). Thirty-three percent of candidates for VT placement did not require surgery when treated with a 6-month course of sulfisoxazole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861918 TI - Preparedness of practicing pediatricians to manage emergencies. AB - To determine pediatrician preparedness to manage emergencies, a nationally representative random sample of 1000 non-hospital-based pediatricians was surveyed about (1) types of emergencies encountered and methods of transport to an emergency facility, (2) availability and use of equipment and medications in the office, and (3) determinants of pediatrician confidence in managing emergencies. The proportion of pediatricians who had encountered specific emergencies ranged from 86% for meningitis to 22% for cardiopulmonary arrest. The majority transported acutely ill children to an emergency department by ambulance. Availability of individual pieces of equipment and medications in offices ranged from 97% for epinephrine 1:1000 to 11% for bone marrow needles for intraosseous access. Combination of equipment available to manage particular emergencies ranged from 61% for severe dehydration to 11% for cardiopulmonary arrest. The equipment available in a pediatrician's office was significantly related to the type of primary work setting. Pediatrician confidence in managing the initial stabilization of emergencies ranged from 58% for seizures to 25% for epiglottitis. Confidence was related significantly to year residency was completed, Advanced Cardiac or Advanced Pediatric Life Support training, work setting, and the availability of equipment in the office. Continuing education regarding initial office management of and equipment for common emergencies should improve the pediatrician's confidence and competence in this area. PMID- 1861919 TI - Emergency medical services and the pediatric patient. III: Resources of ambulatory care centers. AB - Ambulatory care centers have emerged as a new health care resource in many communities. Little information is available about the services that these centers offer to pediatric patients. A national survey of 254 ambulatory care centers was undertaken to determine their characteristics, including the number of pediatric patients seen, staffing patterns, and pediatric equipment and supplies available. Most clinics were located in urban areas and were within 5 miles of a hospital. They were staffed primarily by physicians who were board certified in emergency medicine, internal medicine, or family medicine. Not all centers had registered nurses on duty and few used extended-role nurses or physicians's assistants. The centers saw an average of 18 patients younger than 18 years of age per day. Some ambulatory care centers received emergency medical service and private ambulance calls and encountered serious illness such as chest pain, seizures, and anaphylaxis; the majority, however, handled mainly minor injuries and illnesses. Although most had pediatric equipment and supplies, some did not have a complete set of pediatric resuscitation equipment even though they were part of the emergency system offering care to the pediatric population. PMID- 1861920 TI - Tuberculosis in children 10 years of age and younger: three decades of experience during the chemotherapeutic era. AB - The 863 patients, aged 10 years and younger, treated at the Children's Chest Clinic of Bellevue Hospital during three decades (1953 through 1981) clearly indicated the success of antituberculosis therapy. There were no deaths from tuberculosis. Early treatment is associated with a reduction in the serious forms of disease, eg, meningitis, miliary disease, and bone infections, and with preventing death. Medication was well tolerated: only 1.1% of the patients had adverse reactions, all of which were reversible. Consistent compliance with medication of only 62% of patients is a challenge to the medical profession. Only 22.5% of mycobacterial cultures were positive. Long-term follow-up of patients was rewarding: seven pregnancies with healthy mothers and babies, and no reactivation of tuberculosis by later infections, even those such as measles or pneumonia. The severity of disease was related largely to patient's age (3 years and younger) and intimacy of contact, the highest rate being when the mother was the contact. The long-term experiences emphasizes the value of early identification, therapeutic compliance, and comprehensive contact, tracing in the future elimination of tuberculosis. Prophylactic therapy and close observation should be considered for contacts, especially those exposed to human immunodeficiency virus infections and addicted to drugs. PMID- 1861921 TI - Risk of human immunodeficiency virus type 1 infection among sexual and nonsexual household contacts of persons with congenital clotting disorders. AB - The status of human immunodeficiency virus type 1 (HIV-1) infection at the time of transmission to sexual contacts remains poorly defined. Transmission to nonsexual household contacts has appeared to be rare. A total of 505 sexual and nonsexual contacts of HIV-1-infected hemophiliacs in 349 households was observed. At entry, 10% of 201 sexual partners were anti-HIV-1-positive. Follow-up of 151 uninfected partners during a total of 351 person-years of observation showed no sero-conversions, although there were 13 pregnancies during that period. Eighty seven percent of the seronegative respondents to a detailed questionnaire reported unprotected sexual contact at least occasionally. Among 304 other household members, including 108 parents who helped administer clotting factor concentrates to their children, none was seropositive at entry. Follow-up of 263 showed no seroconversions during a total of 605 person-years of observation. Thus, anti-HIV-1-positive hemophiliacs transmitted to their partners earlier in their course but were not found to do so when prospectively observed. No relationship to level of viremia as indicated by CD4 count, HIV-1 p24 antigenemia, or acquired immunodeficiency syndrome was found. Anti-HIV-1-positive hemophiliacs had not transmitted to their nonsexual household contacts before study entry and did not do so subsequently, indicating that the risk from even close nonsexual contact is extremely low. PMID- 1861923 TI - Passive smoking alters lipid profiles in adolescents. AB - Although cigarette smoking is associated with elevation of plasma lipid levels and changes in lipoprotein distribution, it is not known whether passive smoking is associated with an alteration in lipid profiles. The relation between plasma cotinine, a marker of exposure to tobacco smoke, and lipid profiles was studied in healthy adolescents from a suburban New York high school district who were undergoing preparticipation sports physicals. Forty-four percent of the adolescents reported that one or both parents currently smoked. Eleven percent of the adolescents had plasma cotinine concentrations greater than or equal to 2.5 ng/mL, the level considered indicative of exposure. Adolescents with two smoking parents had significantly higher plasma cotinine concentrations after adjustment for other factors than adolescents whose parents did not smoke. Plasma cotinine concentration greater than or equal to 2.5 ng/mL was associated with an 8.9% greater ratio of total cholesterol to high-density lipoprotein cholesterol (P less than .003) and a 6.8% lower high-density lipoprotein cholesterol (P less than .03). These results suggest that passive smoking, like active smoking, leads to alterations in lipid profiles predictive of an increased risk of atherosclerosis. PMID- 1861922 TI - Cholesterol screening in pediatric practice. AB - Four pediatricians introduced a portable cholesterol analyzer into their group practice. Their experience is described on the basis of 12 months of screening in 1665 children and adolescents. The overall 50th and 90th percentile values for a subgroup of 1406 routinely screened children were 156 and 197 mg/dL, respectively, but there was marked variation in these values among specific age and sex groups. Cholesterol levels decreased by age group during the early teenage years and increased thereafter, these changes occurring at ages approximately 2 years younger for girls than for boys. Further analysis of screening results for 398 sibling pairs demonstrated significant concordance between paired cholesterol levels when classified by the respective age- and sex specific 90th percentile values for each member of the pair. Sibling pairs in which both members' cholesterol values exceeded their 90th percentile value were identified 2.4 times as frequently as expected (confidence interval 1.1 to 4.5, P = .029). The observations reported here indicate that office-based cholesterol screening in a pediatric practice may be both practical and useful, although further consideration of screening criteria is needed. Age- and sex-specific reference values for cholesterol levels during childhood could improve screening results. Special emphasis should be directed toward screening siblings of children in whom high cholesterol levels have been detected. PMID- 1861924 TI - Fish oil treatment of hyperlipidemia in children and adolescents receiving renal replacement therapy. AB - The effect of 8 weeks of daily oral fish oil supplementation in a dose of 3 to 8 g/d on serum lipid levels was studied in 16 patients, 7 to 8 years of age, who had end-stage renal disease and were receiving renal replacement therapy. Fasting serum cholesterol (CHOL), triglyceride (TG) levels, and lipoprotein profiles were measured before therapy, 8 weeks after fish oil supplementation, and 4 weeks after its cessation. During 8 weeks of treatment the mean serum CHOL level did not change. The mean serum TG level, however, decreased significantly (P less than .01) from 236 +/- 31 mg/dL to 171 +/- 21 mg/dL (27.5%). Four weeks after treatment was stopped, the mean serum TG level returned to a value not significantly different from the pretreatment level (208 +/- 30 mg/dL). In a subgroup of 11 excessively hyperlipidemic patients, with serum CHOL and TG levels greater than or equal to 50% of the 90th percentile for age and sex, the mean serum TG level decreased even more (30.8%), from 286 +/- 35 mg/dL to 198 +/- 24 mg/dL (P less than .01), and the mean CHOL/high-density lipoprotein CHOL ratio decreased from 8.4 +/- 1.2 to 7.4 +/- 1.3 (P less than .05). Blood pressure and platelet counts remained stable during the entire study period. Side effects of the treatment were minimal. These results show that dietary fish oil supplementation reduces serum TG levels in young patients receiving renal replacement therapy and improves their "atherogenic" serum lipoprotein profile. PMID- 1861925 TI - Hypercholesterolemia in adolescents: effectiveness of screening strategies based on selected risk factors. AB - This study evaluates the efficacy of the American Academy of Pediatrics' current recommendations for identifying hypercholesterolemia in teenagers. These guidelines advocate a screening strategy that is targeted only at high-risk individuals. Detailed information regarding risk factors for hypercholesterolemia was obtained from 1001 adolescents or their parents at three urban teen clinics during routine health assessments. In addition, serum cholesterol was measured in all adolescents. The population under study was 38.2% Hispanic, 33.5% white, 15.4% black, and 11.3% Asian, with a mean age of 15.6 years (range: 12 through 21 years); 52% were female. Based on the cholesterol values, the study population was divided into two groups: (1) normal cholesterol level, less than 200 mg/dL (n = 937, mean cholesterol value = 157 mg/dL) and (2) elevated cholesterol level, greater than or equal to 200 mg/dL (n = 64, mean cholesterol value = 228 mg/dL, range = 200 through 366 mg/dL). Application of the 1985 American Academy of Pediatrics criteria for selected screening identified 30 of 64 individuals with hypercholesterolemia (sensitivity = 47%). Criteria similar to 1988 recommendations identified 40 of 64 teenagers (sensitivity = 62%). A combination of 1985 and 1988 criteria yielded a sensitivity of 44 of 64, or 69%. The specificity of these criteria was 74%, 60%, and 53%, respectively. Despite the utilization of the 1985, 1988, or a combination of both American Academy of Pediatrics criteria for hypercholesterolemia screening, this study demonstrates that many adolescents with abnormal cholesterol levels would not be identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861926 TI - Family and peer issues among adolescents with spina bifida and cerebral palsy. AB - Increasingly, children with disabling conditions are surviving through childhood into adolescence and beyond. This places increased importance on understanding adolescent, family, and peer relationships, which are critical to healthy development among adolescents in general and to transitions to successful adulthood among youths with physical disabilities in particular. The purpose of this study was to identify the patterns of family and peer interactions. One hundred two youths with spina bifida and 60 adolescents with cerebral palsy between the ages of 12 and 22 completed written psychological measures as well as an in-depth structured interview. Approximately 90% of youths with spina bifida and cerebral palsy resided at home, of whom 80.4% and 72% lived with both parents. Almost without exception, parental relationships were defined as positive, with no difference of attitude noted toward the mother and father. Relationships with parents for teenagers with spina bifida were marked by high levels of dependence on parents for personal care such as bowel programs and, for both groups, low levels of responsibility at home and lack of discussion with parents about sexuality or menstruation. Although friends were viewed as very important by most respondents (approximately 83%), relationships were characterized by extremely limited out-of-school contacts, negligible participation with organized social activities, and a primary orientation toward sedentary activities. Finally, regarding heterosexual relationships, whereas 44.1% of respondents with spina bifida and 54.2% of respondents with cerebral palsy said their friends dated, only 14.7% and 28.3% of study participants indicated that they had ever been on a date and, even for those teenagers, heterosexual social contacts were infrequent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861927 TI - Requiem for a hospital. PMID- 1861928 TI - Infirmary-style sick-child day care: do we need more information? PMID- 1861930 TI - Informing schools about children's chronic illnesses: parents' opinions. AB - Parents of 217 chronically ill children and adolescents were surveyed concerning their opinions about disclosing medical information to schools. The sample consisted of parents of more than one third of the children and adolescents meeting inclusion criteria who were seen at a university-based pediatric clinic during a 10-week period. Parents were asked (1) whether schools need information about 16 health items, (2) who in the school should know, and (3) who should provide this information. Parents' willingness to disclose information was compared with family and child demographic data. Parents strongly believed that (1) teachers need to be informed and (2) parents should be the primary informers. The consensus that schools need information did not vary with family and child demographics. However, parents of children with poor illness prognosis, greater likelihood of emergencies, and visible illnesses were more supportive of disclosure. Most parents indicated that physicians should provide information on 10 of the 16 items. Physicians were viewed as particularly appropriate informers about recognizing emergencies and medication effects. Only 21% of the parents were aware of any prior contact between the medical care giver and the school concerning their child's illness. Thus, parents want schools informed and believe physicians should be involved in providing information. PMID- 1861929 TI - Toward reducing pediatric injuries from firearms: charting a legislative and regulatory course. AB - Each year in the United States, approximately 3000 children and adolescents younger than age 20 die as a result of homicides, suicides, and unintentional injuries from firearms. The young children, relatives, neighbors, and friends of the 30,000 adults killed by firearms each year in the United States are also affected by this uniquely American epidemic. It is estimated that half of all American homes contain 200 million firearms, including 60 million handguns. Increasingly, pediatricians are becoming involved in efforts to reduce the prevalence of injuries from firearms, as parent educators, experts on children and adolescents, and advocates in the political process. This commentary is intended to aid in the last of these roles. The advocacy goal is identified as reducing the accessibility of guns in the environments of children and adolescents. The pros and cons of 17 possible approaches--ranging from mandatory safety courses in schools to handgun bans--are presented. It is concluded that, while there is no perfect approach, many available approaches will help; there is every reason to be both bold and optimistic. PMID- 1861931 TI - Comparison of albuterol and metaproterenol syrup in the treatment of childhood asthma. AB - This study compared the acute and chronic effects of albuterol syrup (2 mg) and metaproterenol syrup (10 mg) three times a day over 28 days in 65 children, aged 6 to 9 years, with mild to moderate asthma. Wright peak flow, symptom scores, and rescue medication use were recorded twice daily during the 28 days; the acute cardiopulmonary effects of these syrups were compared over 8 hours on treatment days 1 and 28. Albuterol syrup produced a significantly greater peak magnitude of bronchodilation than metaproterenol, 29% vs 20% above baseline, respectively, on treatment day 1. Albuterol syrup had a duration of action of at least 8 hours and produced greater bronchodilation than metaproterenol syrup from 2 to 8 hours on both treatment days 1 and 28. The chronotropic effect of metaproterenol was greater than that of albuterol at 1 to 1 1/2 hours postdose on treatment days 1 and 28. There was a trend toward higher morning and evening Wright peak flow measurements during 28 days of treatment in the albuterol group. Side effects of both drugs were comparable. These findings imply therapeutic advantages of albuterol syrup over metaproterenol syrup in currently recommended doses with respect to improvement in pulmonary function, chronotropic effects, and frequency of dosing required to maintain optimum bronchodilation over a 24-hour period. PMID- 1861933 TI - An outbreak of tinea corporis among schoolgirls. PMID- 1861934 TI - Hypothyroidism in otherwise healthy hypercholesterolemic children. PMID- 1861932 TI - Randomized, placebo-controlled trial of iron supplementation in infants with low hemoglobin levels fed iron-fortified formula. AB - In spite of the declining prevalence of iron-deficiency anemia, a large proportion of low-income infants have "low-normal" (11-11.5 g/dL) and "low" (less than 11 g/dL) hemoglobin (Hgb) values. Because most of these infants are fed iron fortified formulas, it was of interest whether additional iron supplementation would enhance Hgb values. A cohort of 334 healthy, inner-city, minority, 6-month old infants, fed iron-fortified formulas, with Hgb values ranging from 9 to 11.5 g/dL, participated in a double-blind, randomized, placebo-controlled trial of supplemental iron at 0, 3, and 6 mg/kg per day for 3 months. Hemoglobin values increased significantly with age, regardless of assignment to placebo or supplemental iron (means for the entire cohort: 6 months 10.9 g/dL, 8 months 11.2, 10 months 11.3, and 12 months 11.4). The proportion of "responders" (Hgb level increased greater than or equal to 1 g/dL) was 34% and did not differ significantly by placebo or iron dose. There were no significant differences in mean corpuscular volume or levels of erythrocyte porphyrins or serum ferritin between treatment groups. The implications of this clinical trial are twofold: (1) screening healthy infants fed iron-fortified formula at the age of 6 months is not justified, regardless of socioeconomic status; (2) the clinical practice of routinely treating low-income, "low-Hgb" infants with iron supplementation, without regard to dietary considerations, is unwarranted. PMID- 1861935 TI - The Weismann-Netter syndrome: a cause of bowed legs in childhood. PMID- 1861936 TI - Cyanide poisoning from a cosmetic nail remover. PMID- 1861937 TI - Scoliosis in beta thalassemia. PMID- 1861938 TI - Verbal dyspraxia in treated galactosemia. AB - Galactosemia is an inborn error of metabolism that causes life-threatening illness a few days after galactose-containing milk is fed to a newborn. Early treatment with a strict lactose-free diet results in rapid improvement, and, until recently, it was thought that the long-term prognosis in such infants was usually good. The speech characteristics of 24 patients treated for galactosemia were examined. Fifty-four percent had the specific speech disorder, verbal dyspraxia. This finding was not related to age at diagnosis, severity of symptoms in the newborn period, or to biochemical control. There may be, however, a relation between dyspraxia and diminished IQ scores observed in the group of patients with dyspraxia judged as "severe." The findings indicate the association of a specific and unusual speech defect with a specific and rare metabolic disorder. PMID- 1861939 TI - Increasing patient knowledge, satisfaction, and involvement: randomized trial of a communication intervention. AB - A brief educational intervention to promote effective communication between physicians, children, and parents during pediatric office visits was designed and tested. A randomized clinical trial involving 141 children (5- to 15-year-olds) tested the effectiveness of the intervention to improve the process and outcome of medical care. The intervention was contained in three brief videotapes (one each for parents, physicians, and patients) and in accompanying written materials. Materials were designed to build skills and motivation for increased child competence and participation during pediatric medical visits. Control subjects saw health education videotapes and received materials comparable in length with those of experimental subjects. Postintervention medical visit process was analyzed using videotapes of visits. Visit outcomes, assessed with standardized instruments and interviews, included children's rapport with physicians, children's anxiety, children's preference for an active health role, children's recall of information, parents' satisfaction with the medical visit, and physician satisfaction. Results indicated that physicians in the intervention group, compared with their counterparts in the control group, more often included children in discussions of medical recommendations (50% vs 29%, t = 2.39, P less than .05); that children in the intervention group, compared with control children, recalled more medication recommendations (77% vs 47%, P less than .01) and reported greater satisfaction and preference for an active health role; and that the intervention and control groups did not differ in parent satisfaction, physician satisfaction, or child anxiety. The results suggest that a brief educational intervention administered during waiting room time can positively impact physician-child rapport and children's preference for an active role in health and their acquisition of medical information. PMID- 1861940 TI - Dietary nucleotide effects upon immune function in infants. AB - Nucleotide (NT) nitrogen, a component of nonprotein nitrogen, accounts for approximately 0.1% to 0.15% of the total nitrogen content of human milk. The results of studies in animals indicate that dietary NTs may be required for maintenance of normal immune function. Thirty-seven healthy term infants were either breast-fed (n = 9) or fed SMA formula supplemented with 33 mg of NTs per liter (n = 13, NT+) or standard SMA formula (n = 15; NT-). At 2 months of age, natural killer cell percent cytotoxicity was significantly higher in the breast fed and NT+ groups compared with the NT- group (41.7 +/- 4.7, 32.2 +/- 3.4, 21.7 +/- 2.2%, respectively). Interleukin-2 production by stimulated mononuclear cells was higher in the NT+ compared with the NT- group at 2 months of age (0.90 +/- 0.28 U/mL, 0.27 +/- 0.11 U/mL, respectively); neither formula-fed group differed significantly from the breast-fed group. Rate of growth and incidence and severity of infections did not differ significantly among dietary groups. Nucleotides may be a component of human milk that contributes to the enhanced immunity of the breast-fed infant. PMID- 1861941 TI - Low-dose zidovudine in children with an human immunodeficiency virus type 1 infection acquired in the perinatal period. AB - This report describes the one-year results of a noncomparative study designed to assess the safety and tolerance of low-dose zidovudine (azidothymidine) given orally to 60 human immunodeficiency virus type 1-infected infants and children. At baseline, the mean age was 1.9 years (+/- 1.4), and all were symptomatic: 43% were P2A and 57% were P2B to F according to the Centers for Disease Control classification. All the patients received zidovudine for at least 6 months, and 52 of them (87%) completed a full year of therapy. The mean duration of follow-up was 346 days (+/- 42) (range, 183 to 366 days). The initial therapy consisted of four daily doses of 100 mg/m2 (400 mg/m2 per day, equivalent to 20 mg/kg per day). However, this treatment was modified when neutropenia or anemia was observed. Twenty-nine children (48%) remained at the initial therapy for the entire study. Zidovudine dosage was adjusted 92 times in the other 31 children (52%), mostly due to neutropenia (83%). Altogether, the time under full-dose therapy represented 81% of the total duration of the protocol for all patients. Children with mild symptoms, P2A at study entry, were more likely to remain under full-dose therapy than children with severe symptoms, P2B to F: the time under full-dose therapy represented 91% of the duration of the protocol for the former group and only 74% for the latter one (P less than .02). No clinical adverse experiences were attributed directly to zidovudine. Thirty-seven children were prescribed trimethoprim-sulfametoxazole as a prophylaxis for Pneumocystis carinii pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1861942 TI - Shoes for children: a review. AB - 1. Optimum foot development occurs in the barefoot environment. 2. The primary role of shoes is to protect the foot from injury and infection. 3. Stiff and compressive footwear may cause deformity, weakness, and loss of mobility. 4. The term "corrective shoes" is a misnomer. 5. Shock absorption, load distribution, and elevation are valid indications for shoe modifications. 6. Shoe selection for children should be based on the barefoot model. 7. Physicians should avoid and discourage the commercialization and "media"-ization of footwear. Merchandising of the "corrective shoe" is harmful to the child, expensive for the family, and a discredit to the medical profession. PMID- 1861943 TI - Remembering as we look ahead: the three E's and firearm injuries. PMID- 1861944 TI - The academic generalist: still an endangered species? PMID- 1861945 TI - The academic generalist: still an endangered species? A response. PMID- 1861946 TI - Baby bottoms and environmental conundrums: disposable diapers and the pediatrician. PMID- 1861947 TI - American Academy of Pediatrics Committee on Injury and Poison Prevention: Children in pickup trucks. PMID- 1861948 TI - American Academy of Pediatrics Committee on Substance Abuse: Hazards of clove cigarettes. PMID- 1861949 TI - American Academy of Pediatrics Committee on Infectious Diseases: The relationship between pertussis vaccine and brain damage: reassessment. PMID- 1861950 TI - American Academy of Pediatrics Committee on Infectious Diseases: The status of acellular pertussis vaccines: current perspective. PMID- 1861951 TI - Summary of the annual meeting. Section on Urology, American Academy of Pediatrics. PMID- 1861952 TI - Encouraging the use of bicycle helmets. PMID- 1861953 TI - Blue mucus. It was in her eyes--not in her head. PMID- 1861954 TI - Fever under 8 weeks of age and urinary tract infection. PMID- 1861955 TI - Blue jeans thighs. PMID- 1861956 TI - Strength training, weight & power lifting, and body building by children and adolescents. PMID- 1861957 TI - Nosedrops and S.I.D.S. PMID- 1861958 TI - Asthma and food sensitivity. PMID- 1861960 TI - [Fundamentals of pathologic anatomy and pathophysiology for implantation success]. PMID- 1861959 TI - Valsalva effect may mimic child abuse. PMID- 1861961 TI - [Computer supported PAR- and prophylaxis concepts]. PMID- 1861962 TI - [Two-year trial of the fluoride-containing varnishes Duraphat and Carex]. AB - Previous studies have shown that topical application of the fluoride varnish Duraphat reduces caries incidence. The aim of the present study was to compare the caries inhibiting effect of a new fluoride varnish (Carex) containing 1.80% fluoride (F) with that of Duraphat (2.26%F). Informed consent was obtained from the guardians of 495 10-12-years-olds in Voss Dental Health District (low F area). The children were randomly allocated to two groups. One group of subjects received six-monthly applications of Duraphat (n = 206), the other Carex (n = 189). Ethical considerations precluded the use of a placebo varnish. All participants received dental examinations including one pair of posterior bitewing radiographs and necessary dental care annually. One trained examiner interpreted bitewing radiographs blindly. Total mean 2-year net DFS increment for 24 posterior approximal surfaces was 1.79 (s = 3.12) in the Duraphat group and 1.53 (s = 2.92) in the Carex group, a difference which was non-significant (P greater than 0.40). Thus it seems that Carex and Duraphat have approximately the same caries-preventive effect on posterior approximal surfaces. PMID- 1861963 TI - [Tetracycline resistance in oral microorganisms in patients with periodontal disease]. AB - Several longitudinal studies have shown that periodontal treatment consisting of surgical and/or nonsurgical debridement of the teeth often is sufficient to prevent continued attachment loss when the patients' oral hygiene measures are good. Nevertheless, some patients will, in spite of excellent oral hygiene measures, continue to show attachment loss. The treatment of these patients has mainly been empirical, and the clinicians have used different kinds of antibiotics for different time intervals to eliminate proposed periodontal pathogens. The preferred antibiotic has been tetracycline. Most bacteria associated with destructive periodontal disease will normally be susceptible to tetracycline at the levels achieved in the gingival crevicular fluid after systemic administration of the antibiotic. Some patients have a microbial flora that will not change enough or be inhibited by these substances. The reason for this may in many cases be the development of antimicrobial resistance. Today 14 genotypes of tetracycline resistance have been found. The resistance is one of three types: active secretion, protection of the ribosomes by proteins and an active breakdown of tetracycline. The third type has recently been discovered as a cryptic gene in the microorganism Bacteroides fragilis. This gene is only expressed after transfer to Eschericia coli. Active breakdown of tetracycline does normally not occur in nature and the global level of the drug is increasing since tetracycline is the second most used antibiotic in the world today. It is therefore of interest to identify tetracycline resistance determinants in the oral cavity and to compare these with tetracycline resistance genes from other sources of human, animal and environmental origin. PMID- 1861964 TI - [Dentistry and European integration]. PMID- 1861965 TI - [Laser therapy in dental practice. What is laser?]. AB - This article briefly discusses laser theory and medical use of different types of laser, laserphysics and laser properties. The indications for lasertherapy as claimed from laser-producers, are numerous. However, we recommend that the effect of treatment with low level laser therapy has to be more documented before general use in a dental practice. PMID- 1861966 TI - [Dental health and the use of dental services among Norwegian recruits in 1988]. AB - The aim of the present study was to describe dental health and dental health behaviour among Norwegian recruits. Data were collected by questionnaires and clinical and radiological examinations among 1067 recruits in 1988. 23.7% of all recruits had no decayed teeth. The average DMFT score was 12.1 (SD = 4.69) and the number of decayed surfaces was 4.1 (SD = 5.97), 46.1% of all recruits had visited the dentist during the last year. The clinical findings (except x-ray scores) were compared with findings from similar studies in 1968 and 1978. The results showed that the dental health improved from 1968 to 1988, while the treatment need was similar in 1978 and 1988. There was little change in the regular dental attendance pattern from 1968 to 1988. PMID- 1861967 TI - [Loss of permanent upper incisors--orthodontic treatment]. AB - After loss of permanent central incisors the treatment of choice could be either orthodontic closure or maintenance of the gap for a replacement-prosthetic, autotransplantation or implant. Cases suitable for orthodontic closure are Angle C1 I space deficiency cases and some C1 II cases, all of these requiring normal size and shape of the lateral. C1 III cases, cases with completely developed ideal occlusion and cases with excess of space are unsuitable for orthodontic closure, as are small pegshaped laterals. Different treatment alternatives are presented, illustrated with treated cases. When one or two central incisors are missing, there will be no treatment alternative giving a 100% satisfactory result. Orthodontic closure, however, proves to be a favourable solution, concerning both long-term prognosis, esthetics and function. PMID- 1861968 TI - [Allogeneic transplantation--two case reports]. AB - After a brief discussion on the transplantation of teeth, two cases of allogeneic transplantation, respectively from brother to sister, and from daughter to mother, are presented. Based on the two cases and a limited number of case histories found in dental literature, it is suggested that immunological screening of donor and recipient may help improve the prognosis of allogeneic transplantation of teeth. PMID- 1861969 TI - Mechanisms and management of pain due to inflammation. PMID- 1861970 TI - Dentistry in Jamaica. PMID- 1861971 TI - Retirement planning for dentists. PMID- 1861972 TI - Management of coronal tooth fractures. PMID- 1861973 TI - Mapping of the DNA linking tyrosine residue of the PRD1 terminal protein. AB - DNA replication of PRD1, a lipid-containing phage, is initiated by a protein priming mechanism. The terminal protein encoded by gene 8 acts as a protein primer in DNA synthesis by forming an initiation complex with the 5'-terminal nucleotide, dGMP. The linkage between the terminal protein and the 5' terminal nucleotide is a tyrosylphosphodiester bond. The PRD1 terminal protein contains 13 tyrosine residues in a total of 259 amino acids. By site-directed mutagenesis of cloned PRD1 gene 8, we replaced 12 of the 13 tyrosine residues in the terminal protein with phenylalanine and the other tyrosine residue with asparagine. Functional analysis of these mutant terminal proteins suggested that tyrosine-190 is the linking amino acid that forms a covalent bond with dGMP. Cyanogen bromide cleavage studies also implicated tyrosine-190 as the DNA-linking amino acid residue of the PRD1 terminal protein. Our results further show that tyrosine residues at both the amino-terminal and the carboxyl-terminal regions are important for the initiation complex forming activity. Predicted secondary structures for the regions around the DNA linking amino acid residues were compared in three terminal proteins (phi 29, adenovirus-2, and PRD1). While the linking amino acids serine-232 (phi 29) and serine-577 (adenovirus-2) are found in beta-turns in hydrophilic regions, the linking tyrosine-190 of the PRD1 terminal protein is found in a beta-sheet in a hydrophobic region. PMID- 1861974 TI - The htrM gene, whose product is essential for Escherichia coli viability only at elevated temperatures, is identical to the rfaD gene. AB - We have identified a new E. coli gene, htrM. The htrM gene was identified because its insertional inactivation by the Tn5 transposon results in E. coli's inability to form colonies at temperatures above 43 degrees C. The corresponding htrM+ gene was cloned on the basis of its ability to correct the temperature-sensitive phenotype of the htrM::Tn5 insertion mutations. The htrM gene has been mapped to 81.2 min on the conventional E. coli genetic map. It was sequenced and shown to code for an acidic, 34,893-Da polypeptide. Three transcriptional starts were located 48, 90 and 123 nucleotides upstream of the ATG, initiation codon referred to as the P1, P2 and P3(hs) promoters, respectively. The -10 and -35 regions of the P1 promoter bear a close similarity to the E sigma 70-recognized consensus sequences, while the -12 region of the P2 promoter resembles the consensus promoter sequence transcribed by the rpoN gene product. Transcripts of the htrM gene accumulate with increasing temperature. The -10 and -35 regions of the P3(hs) promoter, represented by nucleotides 160 to 130 upstream of the ATG initation codon, are similar to the E sigma 32-recognized consensus sequences. The sigma 32 transcription factor is essential for maximal htrM gene transcription, since htrM RNA transcripts are made at reduced rates in a rpoH null mutant background. Surprisingly, the htrM gene turns out to be identical to rfaD, whose product is required for the biosynthesis of the ADP-L-glycero-D manoheptose lipopolyaccharide precursor [Pegues et al. (1990) J. Bacteriol. 172, 4652-4660]. PMID- 1861975 TI - DNA binding properties of the integrase proteins of human immunodeficiency viruses types 1 and 2. AB - Integration of retroviral DNA into the host chromosome requires the integrase protein (IN). We overexpressed the IN proteins of human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) in E. coli and purified them. Both proteins were found to specifically cut two nucleotides off the ends of linear viral DNA, and to integrate viral DNA into target DNA. This demonstrates that HIV IN is the only protein required for integration of HIV DNA. Although the two types of IN proteins have only 53% amino acid sequence similarity, they act with equal efficiency on both type 1 and type 2 viral DNA. Binding of IN to DNA was tested: purified IN does not bind very specifically to viral DNA ends. Nevertheless, only viral DNA ends are cleaved and integrated. We interpret this as follows: in vitro quick aspecific binding to DNA is followed by slow specific cutting and integration. IN can not find viral DNA ends in the presence of an excess of aspecific DNA; in vivo this is not required since the IN protein is in constant proximity of viral DNA in the viral core particle. PMID- 1861976 TI - Preferential recognition of I.T base-pairs in the initiation of excision-repair by hypoxanthine-DNA glycosylase. AB - Double-stranded synthetic oligonucleotides with a centrally located dIMP residue in a 5'-32P-labeled strand were employed as substrates for hypoxanthine-DNA glycosylase. The enzyme activity was monitored by the generation of a piperidine sensitive site in the labeled oligonucleotide. The enzyme was purified approximately 5000-fold from calf thymus. The purified enzyme removed efficiently a hypoxanthine base residue from an I.T base pair, but 15-20 times more slowly from an I.C base pair. Similar results were obtained with oligonucleotides in which the deoxyinosine residue was placed in different surrounding nucleotide sequences. The enzyme had no detectable activity on mismatched G.T, A.G or A.C base pairs. The data indicate that hypoxanthine-DNA glycosylase participates in the repair of deaminated adenine residues in DNA. PMID- 1861977 TI - The use of a synthetic tRNA gene as a novel approach to study in vivo transcription and chromatin structure in yeast. AB - To monitor in vivo transcription and chromatin structure of yeast tRNA genes, we constructed a synthetic tRNA gene that can be used as a reporter. Constructs in which this synthetic tRNA gene is combined with different flanking regions can be integrated into the genome as single copies. The artificial tRNA gene is tagged by the insertion of an intron-like sequence that cannot be spliced out from the precursor and transcripts can thus be identified and quantitated. By several criteria, the artificial tRNA gene behaves like a resident tRNA gene. By measuring the accessibility towards DNaseI in chromatin, we found that the artificial tRNA gene exhibits the same characteristic pattern as resident tRNA genes. Three DNaseI-sensitive sites across the transcribed part of the gene and the immediate flanking regions reflect the formation of the stable transcription complex; positioned nucleosomes are observed in the upstream flanking region. We are confident that the system we have established will prove useful for studying regulatory aspects of tRNA gene expression as well as aspects of pre-tRNA processing and splicing. PMID- 1861978 TI - Striking homology of the 'variable' N-terminal as well as the 'conserved core' domains of the mouse and human TATA-factors (TFIID). AB - A complementary DNA (cDNA) encoding a mouse TFIID (mIID) was isolated from mouse brain cDNA libraries. The 316 amino acid sequence deduced from cDNA sequences revealed the presence of an amino-terminal region enriched in serine, threonine, and proline (STP-cluster), an uninterrupted stretch of 13 glutamine residues (Q run), a second STP-cluster, and a conserved carboxy-terminal region. Amino acid sequences of the first STP-cluster and the conserved carboxy-terminal region were identical to those of the human TFIID (hIID). However, the Q-run was considerably shorter than that in hIID and sequences in the second STP-cluster diverged from those of the hIID. The murine TFIID transcript is expressed as a 2 kilobase poly(A)+ RNA in the mouse brain. Southern blot analysis identified a single gene copy per haploid mouse genome. PMID- 1861979 TI - A developmentally regulated gene encodes the dictyostelium homolog of yeast ribosomal protein S4 and mammalian LLRep3 proteins. AB - We report the sequence and expression of a single-copy gene from Dictyostelium discoideum which encodes the homolog of yeast ribosomal protein S4, a protein located on the small ribosomal subunit and known to play an important role in maintaining translational fidelity. Over a highly conserved central region, the Dictyostelium protein has 78% sequence similarity to the yeast protein and 83% sequence similarity to mammalian S4 protein homologs, the LLRep3 proteins. The Dictyostelium gene encodes a polypeptide 28,717 Da in size and hence this ribosomal protein has been named rp29. The N-terminal sequence of the Dictyostelium rp29 protein is extended by 61 amino acids and 14 amino acids compared to the mammalian and yeast proteins, respectively, and the C-terminus is correspondingly 15 amino acids or 2 amino acids shorter. Although the coding region of the rp29 gene is present on a single exon, a 157bp intron interrupts the 5' untranslated region and unusually contains four direct repeats of the sequence TCAATCT. The gene is expressed maximally during vegetative growth but a second peak of expression also occurs late in development which is restricted to prestalk cells; rp29 is the first Dictyostelium ribosomal protein gene reported which shows prestalk-specific developmental expression. During each round of expression, only a single 0.9kb transcript is produced which is similar in size to the yeast S4 ribosomal protein transcript (0.8kb) but markedly smaller than the mammalian LLRep3 mRNA (1.7kb) due to a much shorter 5' untranslated region. PMID- 1861980 TI - K-tuple frequency in the human genome and polymerase chain reaction. AB - The frequency occurrences of K-tuple (overlapping sequences of defined length, K) were computed from the known human genome sequences. The significance of these frequencies for the whole human genome was tested by polymerase chain reaction (PCR). A computer programs based on these results was written to choose primers to amplify DNA target sequences, either of human genes or of human infectious agents. The software also gave nested primer sequences which were used to synthesize non radioactive probes by PCR. We applied these two methods, primer selection and non radioactive probes, to easily and quickly set up very efficient PCR sets to work in the human genome context. PMID- 1861983 TI - A sequence assembly and editing program for efficient management of large projects. AB - We describe a sequence assembly and editing program for managing large and small projects. It is being used to sequence complete cosmids and has substantially reduced the time taken to process the data. In addition to handling conventionally derived sequences it can use data obtained from Applied Biosystems,Inc. 373A and Pharmacia A.L.F. fluorescent sequencing machines. Readings are assembled automatically. All editing is performed using a mouse operated contig editor that displays aligned sequences and their traces together on the screen. The editor, which can be used on single contigs or for joining contigs, permits rapid movement along the aligned sequences. Insertions, deletions and replacements can be made in individual aligned readings and global changes can be made by editing the consensus. All changes are recorded. A click on a mouse button will display the traces covering the current cursor position, hence allowing quick resolution of problems. Another function automatically moves the cursor to the next unresolved character. The editor also provides facilities for annotating the sequences. Typical annotations include flagging the positions of primers used for walking, or for marking sites, such as compressions, that have caused problems during sequencing. Graphical displays aid the assessment of progress. PMID- 1861982 TI - The effect of the length of direct repeats and the presence of palindromes on deletion between directly repeated DNA sequences in bacteriophage T7. AB - The frequency of genetic deletion between directly repeated DNA sequences in bacteriophage T7 was measured as a function of the length of the direct repeat. The non-essential ligase gene (gene 1.3) of bacteriophage T7 was interrupted with pieces of synthetic DNA bracketed by direct repeats of various lengths. Deletion of these 76 bp long inserts was too low to be measured when the direct repeats were less than 6 bp long. However, the frequency of deletion of inserts with longer direct repeats increased exponentially as the length of the repeats increased from 8 to 20 bp. When inverted repeats (palindromes) were designed in the midst of the insert there was essentially no increase in deletion frequency between 10 bp direct repeats. But, the same palindromic sequences increased the deletion frequency between 5 bp direct repeats by at least two orders of magnitude. Thus, in this system homology at the endpoints is a more important determinant of deletion frequency than is the presence of palindromes between the direct repeats. PMID- 1861981 TI - Distribution and characterization of helix-loop-helix enhancer-binding proteins from pancreatic beta cells and lymphocytes. AB - Transcription of a number of mammalian genes is controlled in part by closely related DNA elements sharing a CAxxTG consensus sequence (E boxes). In this report, we survey cell extracts from a variety of mammalian cell lineages for ability to bind to the E box denoted IEB1/kappa E1, which plays an important role in expression of both insulin and immunoglobulin kappa genes. Insulin enhancer factor 1 (IEF1), a binding activity previously identified in beta cells, was also present in pituitary endocrine cells but absent in 7 other mammalian cell lines tested. A distinct binding activity, lymphoid enhancer factor 1 (LEF1), was observed in several lymphoid cell lines, but was absent from all nonlymphoid cells tested. IEF1 and LEF1 were distinct according to electrophoretic mobility, and DNA binding specificity. As previously reported, both beta cell and lymphoid cell factors are recognized by antibodies to helix-loop-helix (HLH) proteins, indicating that they may contain functional helix-loop-helix dimerization domains. To directly demonstrate this, we showed that the binding factors are able to interact in vitro with the HLH domain of a characterized HLH protein. These results support the notion that HLH proteins play a key role in cell specific transcriptional regulation in cells from endocrine and lymphocyte lineages. PMID- 1861984 TI - Nucleotide preferences in sequence-specific recognition of DNA by c-myb protein. AB - Using a binding site selection procedure, we have found that sequence-specific DNA-binding by the mouse c-myb protein involves recognition of nucleotides outside of the previously identified hexanucleotide motif. Oligonucleotides containing a random nucleotide core were immunoprecipitated in association with c Myb, amplified by the Polymerase Chain Reaction and cloned in plasmids prior to sequencing. By alignment of sequences it was apparent that additional preferences existed at each of three bases immediately 5' of the hexanucleotide consensus, allowing an extension of the preferred binding site to YGRCVGTTR. The contributions of these 5' nucleotides to binding affinity was established in bandshift analyses with oligonucleotides containing single base substitutions; in particular, it was found that replacement of the preferred guanine at position -2 with any other base greatly reduced c-Myb binding. We found that the protein encoded by the related B-myb gene bound the preferred c-Myb site with similar affinity; however, B-Myb and c-Myb showed distinct preferences for the identity of the nucleotide at position -1 relative to the hexanucleotide consensus. This study demonstrates that the c-Myb DNA-binding site is more extensive than recognised hitherto and points to similar but distinct nucleotide preferences in recognition of DNA by related Myb proteins. PMID- 1861985 TI - Single-base mutational analysis of cancer and genetic diseases using membrane bound modified oligonucleotides. AB - A convenient format for the detection of PCR amplified sequences is the hybridization of the PCR products to oligonucleotide probes which are immobilized on a solid phase. We describe a new method for site-specific attachment of such probe oligonucleotides to nylon membranes. The method is based on the formation of an amide bond between carboxyl groups present on the membranes and amino linkers situated on the 5' end of the oligonucleotides. The covalent attachment is via a carbodiimide mediated condensation. The single, 5' end attachment of the oligonucleotides to the membrane surface leaves the probe free to interact with complementary sequences, thus increasing the hybridization efficiency relative to methods where heat or ultraviolet light is used for non-specific fixation. Using biotinylated PCR products in hybridization reactions along with a non-radioactive chemiluminescent detection system, high efficiency hybridization is obtained as well as a very good signal to noise ratio. The method has been applied successfully to the detection of RAS point mutations, cystic fibrosis deletion and point mutations and others. The sensitivity, simplicity and reproducibility of this method make it an ideal tool for the diagnosis of infectious and genetic diseases, as well as analysis of mutations in neoplasias, HLA typing and other areas. PMID- 1861987 TI - Sequence of a tRNA gene cluster in Trypanosoma brucei. PMID- 1861986 TI - Transcription inhibition of the somatic-type phosphoglycerate kinase 1 gene in vitro by a testis-specific factor that recognizes a sequence similar to the binding site for Ets oncoproteins. AB - To elucidate the mechanism by which transcription of the somatic-type phosphoglycerate kinase 1 gene is inactivated during mammalian spermatogenesis, we examined the presence of specific transcription inhibitor(s) in the testis by a cell-free transcription system. Transcription of the mouse phosphoglycerate kinase 1 gene using nuclear extracts of the rat liver was significantly inhibited by the addition of testis extracts, whereas brain extracts had little effect. Transcription inhibition required the binding of a testis-specific factor, designated TIN-1, to the region between positions -268 and -259 relative to transcription initiation site at +1. This region had the sequence 5'-AGGAAGTTCC 3' that includes an inverted repeat of the binding motif, 5'-GGAA-3', for the oncoprotein Ets. A UV-crosslinking experiment revealed that 43- and 45-kDa polypeptides present in testis extracts bind to that sequence. These results suggest that a testis-specific transcription inhibitor TIN-1 inactivates the phosphoglycerate kinase 1 gene in the mammalian spermatogenic pathway. PMID- 1861988 TI - Conserved KRAB protein domain identified upstream from the zinc finger region of Kox 8. PMID- 1861989 TI - M.EcoP15 methylates the second adenine in its recognition sequence. PMID- 1861990 TI - 36B4 cDNA used as an estradiol-independent mRNA control is the cDNA for human acidic ribosomal phosphoprotein PO. PMID- 1861991 TI - Location of the fpg gene on the Escherichia coli chromosome. PMID- 1861992 TI - Nucleotide sequence of beta-lactamase regulatory genes from staphylococcal plasmid pI258. PMID- 1861993 TI - cDNA and predicted amino acid sequences of the human ribosomal protein genes rpS12 and rpL17. PMID- 1861994 TI - Gel electrophoresis using a fluorescence agent for analysis and purification of non-labeled synthetic DNA fragments. PMID- 1861995 TI - Fingerprinting of diverse species with DNA probes generated from immobilized single-stranded DNA templates. PMID- 1861996 TI - Non-immunological precipitation of protein-DNA complexes using glutathione-S transferase fusion proteins. PMID- 1861997 TI - Improved detection of HBV DNA by PCR after microwave treatment of serum. PMID- 1861998 TI - Incomplete kinase labelling of PCR primers yields 'doublet' artifacts in denaturing gradient gels. PMID- 1861999 TI - 'Touchdown' PCR to circumvent spurious priming during gene amplification. PMID- 1862000 TI - Improved efficiency for single-sided PCR by creating a reusable pool of first strand cDNA coupled to a solid phase. PMID- 1862001 TI - A rapid membrane-based viral RNA isolation method for the polymerase chain reaction. PMID- 1862002 TI - A novel rapid method for detection of PCR products. PMID- 1862003 TI - Dinucleotide repeat polymorphism at the human GLUT2 locus. PMID- 1862004 TI - Dinucleotide repeat polymorphism at the human CTLA4 gene. PMID- 1862006 TI - Dinucleotide repeat polymorphism at the human cardiac beta-myosin gene. PMID- 1862005 TI - Tetranucleotide repeat polymorphism at the human c-fes/fps proto-oncogene (FES). PMID- 1862007 TI - Dinucleotide repeat polymorphism in the IL-2R beta gene. PMID- 1862008 TI - Dinucleotide repeat polymorphism at the D21S198 locus. PMID- 1862009 TI - Dinucleotide repeat polymorphism at the D9S55 locus. PMID- 1862011 TI - Colchicine: a state-of-the-art review. AB - Colchicine is an ancient drug that is attracting renewed interest because of its actions at a subcellular level. Specifically, it interferes with microtubule growth and therefore affects mitosis and other microtubule-dependent functions. Various mechanisms have been proposed to account for the action of colchicine in acute gouty arthritis, its interaction with cellular membrane and cyclic 3',5' adenosine monophosphate, and its action in amyloidosis. Pharmacokinetic studies have been relatively limited and their results somewhat contradictory, with mean terminal elimination half-lives of 19 minutes to 9 hours being reported. Some of these differences may be attributed to assay difficulties. Colchicine can cause gastrointestinal side effects and should be used with care to protect patients from toxic doses. Colchicine-induced myopathy and neuropathy may be more frequent than previously recognized, and therefore patients receiving long-term therapy should be monitored carefully. Bone marrow depression has been reported, primarily in cases of acute colchicine intoxication, and intravenous administration of the drug has been associated with severe pancytopenia and death. Colchicine intoxication causes multiple organ failure. Because of its cytogenic effects and reported association with Down's syndrome, the agent should not be used by pregnant women. PMID- 1862012 TI - Pharmacotherapy of otitis media. AB - The clinical manifestations of acute otitis media and otitis media with effusion are the result of abnormal eustachian tube function most often caused by inflammation from infection or allergy. The majority of cases involve bacterial infection of the middle ear caused by Streptococcus pneumoniae, Haemophilus influenzae, or Branhamella catarrhalis. Nearly half of all children will have had at least one episode of acute otitis media by 1 year of age, and over 70% by 3 years of age. The signs and symptoms include pain with rubbing or tugging at the ear, fever, irritability, lethargy, and hearing loss. The primary therapy for acute otitis media and otitis media with effusion is antibiotics with the goal of preventing possible complications and providing symptomatic relief. Amoxicillin remains the initial drug of choice in communities where beta-lactamase-producing strains of the common middle ear pathogens are infrequently isolated. If resistant organisms are prevalent, cefaclor, amoxicillin-clavulanate, or cotrimoxazole should be selected. Adjuvant agents such as decongestants have not been shown to provide additional therapeutic benefit. Children who develop chronic otitis media may require prophylactic antibiotic therapy and insertion of typanostomy tubes. PMID- 1862013 TI - Perspectives on geriatric pharmacotherapy. AB - In the United States the population over 85 years of age use a disproportionately large percentage of health care resources, including drugs. The elderly take approximately one-third of all medications. Among other factors, the need for several agents predisposes them to adverse drug reactions and drug interactions. Sequelae from drug usage in the elderly are more common than in younger patient populations, and often result in hospitalization. Careful patient monitoring is imperative for optimum pharmacotherapy in elderly patients. PMID- 1862014 TI - Management of patients with Alzheimer's disease. AB - Alzheimer's disease represents the most common cause of dementia in the elderly. Current estimates suggest that nearly 50% of those over age 85 years have the disorder. Many gaps still exist in our understanding of its etiology and management. Scientific discoveries that once seemed to promise effective treatments have not lived up to our expectations. There are, however, many therapeutic interventions (environmental and pharmacologic) that can greatly enhance the quality of the lives of patients with Alzheimer's disease and that of their families. PMID- 1862017 TI - Central issues relevant to clinical pharmaceutical scientist training programs. PMID- 1862015 TI - Evaluation of an ibuprofen controlled-release tablet and placebo in postoperative oral surgery pain. AB - Seventy-four outpatients with postoperative pain after oral surgery were randomly assigned, on a double-blind basis, to receive a single oral dose of a controlled release tablet (CRT) containing 600 mg ibuprofen, two 600-mg ibuprofen CRTs, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medicating. Estimates of total and peak analgesia were derived from these subjective reports. The ibuprofen CRTs (600 and 1200 mg) had manifested an analgesic effect by hour 1 and their efficacy persisted for 12 hours. Comparable effect for the two ibuprofen CRT dosages could suggest a plateau in analgesia at the 600-mg level or a lack of upside assay sensitivity. Duration of effect was longer for the CRTs than we have previously observed with conventional ibuprofen tablets. Adverse effects were transitory and consistent with the known pharmacologic profile of the medication evaluated. PMID- 1862018 TI - [The edentulous mandible: biomorphological considerations and clinical applications]. PMID- 1862016 TI - Effects of age on reporting of adverse clinical events: results from two postmarketing surveillance methods. AB - Two postmarketing surveillance methods were employed to determine the possible effects of age on reports by outpatients of adverse clinical events (ACEs) occurring shortly after treatment with targeted oral antibiotics or tricyclic antidepressants. One approach involved staff-initiated interviews of patients by telephone and the other involved patient-initiated telephone calls to report possible adverse drug reactions. Regardless of the method, the interviews obtained ACE reports both spontaneously and by review of organ systems. Both postmarketing methods confirmed monotonic relationships for age with treatment duration on the target drugs and with the number of concurrent medications. However, the expected positive correlation between age and spontaneously reported ACEs was evident only in the self-monitoring patients who initiated reports. Negative correlations between age and the number of reported valid ACEs were seen in six independent samples, whereas only two demonstrated a positive relationship. This disparity may elucidate a critical methodologic problem: careful attention must be paid to the means of eliciting information about possible adverse clinical events before attempting to study adverse drug reactions, which are necessarily a subset of ACEs. PMID- 1862010 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1862019 TI - Childhood leprosy in northern India. AB - During a period of eight years, 132 new leprosy cases were detected in children ages 3 to 19 years. Borderline tuberculoid leprosy was present in 59%, tuberculoid in 7.6%, and indeterminate type in 3.8% patients. Single skin lesions were seen in a significant number (43.9%) of patients. Bacillus-positive disease was detected more often (17.4%) than in adults. A high frequency (66.6%) of nerve involvement was also detected. Deformities were uncommon. Males were more often affected than females, especially in the ages 10 to 14 and 15 to 19 years. A history of contact was available in only 19.7% patients, and the contact was intrafamilial in 84.6%. PMID- 1862020 TI - Mahogany discoloration of the skin due to the defensive secretion of a millipede. AB - An 8-year-old boy developed a sudden mahogany discoloration of his skin after exposure to defensive secretions of a millipede. The mechanisms and the composition of the secretion and other clinical features are briefly reviewed. PMID- 1862022 TI - McCune-Albright syndrome with multiple bilateral cafe au lait spots. AB - A 7-week-old infant developed hyperpigmented lesions at 5 days of age that gradually progressed to sharply demarcated, medium-brown macules of unusual configuration involving the neck, trunk, buttocks, upper arms, and right upper thigh. A biopsy specimen of a representative lesion showed changes of epidermal melanosis consistent with cafe au lait spot. At age 15 months the patient developed a limp. Roentgenographic evaluation showed widespread, bilateral changes of fibrous dysplasia, most severe in the right pelvis, femur, and tibia. At the present time he has no evidence of precocious puberty or other endocrinopathies. Despite the absence of endocrine abnormalities, these findings are consistent with a diagnosis of McCune-Albright syndrome with extensive bony and cutaneous lesions. PMID- 1862021 TI - Multiple pyogenic granulomata in childhood. AB - Multiple pyogenic granulomata are rare. Satellite lesions are infrequently associated with trauma to or treatment of the primary lesion. Rare cases of disseminated pyogenic granulomata have been reported. We report the occurrence of numerous, discrete, pyogenic granulomata in two young boys at locations remote from the primary excision site, and review the literature on multiple pyogenic granulomata. In patient no. 1, new lesions seemed to develop from 2- to 4-mm capillary hemangiomas both within and outside of a port-wine stain. Patient no. 2 involves a previously unreported occurrence of numerous facial lesions. PMID- 1862024 TI - Congenital malalignment of the great toenails: case report and literature review. AB - A 10-year-old black boy had congenital malalignment of the great toenails (CMGTN). It is important to recognize this condition since several nail disorders can occur concurrently with and/or clinically mimic it. Treatment is dependent on the severity of the condition, and includes conservative management and subsequent examination to detect CMGTN-associated complications for patients with mild lateral deviation of the nail plate, or surgical realignment for individuals with either marked nail plate deviation or condition-related disabling sequelae. PMID- 1862023 TI - Congenital malalignment of the great toenails. AB - Congenital malalignment of the great toenails is a disorder in which malalignment of the nail matrix results in angular lateral nail plate growth. The consequence is onychodystrophy, which may progress to onychogryphosis and chronic ingrown toenails. There has been debate as to whether the condition is inherited or acquired in utero secondary to improper fetal positioning. A 6-year-old boy and his father, both of whom have this disorder, are discussed. PMID- 1862025 TI - Type 1 diabetes mellitus associated with livedo reticularis: case report and review of the literature. AB - Livedo reticularis (LR) has been associated with numerous systemic diseases. Its relationship to diabetes mellitus (DM), however, has been poorly characterized. We report a case of LR in a 17-year-old with type 1 DM. PMID- 1862026 TI - Severe febrile Mucha-Habermann's disease in children: case report and review of the literature. AB - Mucha-Habermann disease, or pityriasis lichenoides et varioliformis acuta, is usually a benign, papulosquamous, cutaneous disorder. It has also been reported in a severe form with fever and systemic symptoms both in children and adults. We report a 12-year-old boy with the febrile, ulceronecrotic type. A review of similar cases in the literature shows a 16% frequency of acute necrotic lesions, as well as rare complications such as fever, superinfected lesions, bacteremia (most often with Staphylococcus aureus), and rheumatologic manifestations such as arthritis and scleroderma. There is no definitive treatment, but tetracycline, erythromycin, methotrexate, and ultraviolet light are used most frequently. The most common histologic feature is mononuclear perivascular infiltrates. Mucha Habermann disease can mimic other common entities such as varicella and insect bites. PMID- 1862027 TI - Poikiloderma congenitale: case report and review of the literature. AB - Since birth an 8-year-old girl had a rash on both cheeks, consistent clinically and histologically with poikiloderma. She also had visual impairment to the extent of light perception only, due to microthalmia and dense scleralization of the corneas. These features were considered consistent with a diagnosis of Rothmund-Thomson syndrome. PMID- 1862028 TI - Treatment of spider telangiectases in children using the flashlamp-pumped pulsed dye laser. AB - Twelve children 2 to 10 years of age with spider telangiectases of the face were treated with a flashlamp-pumped pulsed dye laser at a wavelength of 585 nm and a pulse width of 450 microsec. Complete resolution of the telangiectases was noted in all 12 patients, without scarring or permanent pigmentary alteration of the skin. PMID- 1862029 TI - Therapeutic efficacy, secondary effects, and patient acceptability of 10% sulfur in either pork fat or cold cream for the treatment of scabies. AB - Twenty-six children with scabies and 32 contacts were treated with 10% sulfur in cold cream. A 100% clinical cure rate was observed, although 56.8% of patients experienced some kind of mild, transient cutaneous reaction. An additional 25 children with scabies and 28 contacts were treated with 10% sulfur and 1% salicylic acid in pork fat. Of these, 88% were clinically cured and 73.5% had some cutaneous adverse effects. In both groups, most adverse effects were related to skin dryness or postscabetic reaction. The cold cream base was more acceptable to patients than the pork fat base. However, the pork fat base was significantly cheaper and easier to obtain than the cold cream base, and 238 times less expensive than the cheapest commercial scabicidal medication available in the United States. PMID- 1862030 TI - Transverse striate leukonychia associated with cancer chemotherapy. PMID- 1862031 TI - What syndrome is this characteristic of? Dyskeratosis congenita. PMID- 1862032 TI - Exophytic scalp tumor in a newborn. PMID- 1862033 TI - Pityriasis versicolor in the pediatric age. AB - Pityriasis versicolor (PV) is a superficial mycosis, theoretically unusual in children. Epidemiologic and clinical data for children with PV over 11 years was collected. Some explanations are given for the conditions that favored this mycotic infection in children. This study confirms that the face is a usual site of PV in children, in contrast to its rarity as a site in adults. Clinical features are variable and similar to adults. Both sexes are equally affected. The family history is often positive for PV. PMID- 1862034 TI - Perianal streptococcal dermatitis: diagnostic considerations. PMID- 1862037 TI - Lichen nitidus actinicus. PMID- 1862036 TI - Long-term follow-up of a patient with lymphomatoid papulosis. PMID- 1862035 TI - Warts in blacks versus whites. PMID- 1862039 TI - Cardiac transplantation. How recipients are selected. AB - Your patients with heart disease may ask about transplantation. Those who are potential candidates need a physician who knows enough about the selection system to get them into it. For other patients, an explanation of why the procedure is contraindicated in their case can help them refocus on compliance with recommended therapy. The authors discuss the principles of recipient selection. PMID- 1862038 TI - Bell's palsy. A diagnosis of exclusion. AB - In cases of acute unilateral facial weakness, a careful and systematic evaluation is necessary to identify the cause. Idiopathic facial paralysis (Bell's palsy) is a diagnosis of exclusion. It is also the most common cause of unilateral facial weakness seen by primary care physicians. The most important aspect of initial treatment is eye protection. Administration of systemic oral corticosteroids may lessen severity and duration of symptoms. PMID- 1862040 TI - Farm injuries. How can the family farm be made a safer place? AB - Farming is a dangerous life-style and occupation for children and adults. Dangerous situations are taken in stride and considered part of life on a family farm. Regulatory and educational programs and funding have been minimal in the United States. Physicians have been a major force in accident-prevention efforts in other segments of society and can be instrumental in preventing farm injuries as well by extending these educational efforts to rural communities. PMID- 1862041 TI - Burning pain in an extremity. Breaking the destructive cycle of reflex sympathetic dystrophy. AB - The pathogenesis of reflex sympathetic dystrophy is controversial, but the condition can result from a major or seemingly minor injury to a limb, or even an insult to an organ, such as stroke or myocardial infarction. Onset can be sudden or insidious. The syndrome is characterized primarily by localized, deep, burning pain in a limb--pain that may not follow any logical distribution. Nonpitting edema, skin hyperesthesia, and guarding of the limb usually accompany the pain. If treatment is not instituted, deformity, contracture, and wasting of the limb can eventually occur. With appropriate therapy, the process can be stopped and often reversed. The keys are a high index of suspicion, early diagnosis, and aggressive treatment. PMID- 1862042 TI - Acid peptic disease in adolescents. How to avoid misdiagnosis and undertreatment. AB - Acid peptic disease in adolescents may be more common than previously recognized. However, appropriate medical attention is often delayed because of misdiagnosis and undertreatment. Thorough questioning of adolescent patients is important to elicit a complete description of symptoms. Endoscopy or intraluminal pH monitoring may be necessary to establish a diagnosis of gastroesophageal reflux disease or peptic ulcer. Therapy with histamine receptor antagonists, especially ranitidine (Zantac), is recommended. Antireflux surgery may be needed to prevent potential long-term gastrointestinal damage. Patients with duodenal ulcer should also be advised to make life-style changes to avoid recurrence of disease later in life. PMID- 1862043 TI - Office dermatologic surgery and laser therapy. AB - As the result of a dramatic increase in the incidence of skin cancer and the need for effective outpatient surgical treatment, dermatology is now a surgical as well as a medical specialty, and many procedures are commonly performed on an outpatient basis. Mohs micrographic surgery is used to remove basal cell and squamous cell carcinomas, and the resulting cure rates are high. Excisional biopsy can facilitate the early diagnosis of melanoma, while it is still in clinical stage I. Carbon dioxide lasers are commonly used to destroy epidermal lesions and yellow light lasers to destroy hemangiomas or other vascular malformations. Facial chemical peel (chemexfoliation) with trichloroacetic acid can improve the appearance of photoaged skin. PMID- 1862044 TI - Febrile seizure. Caring for patients--and their parents. AB - Management of febrile seizure involves diagnosis and treatment of the underlying cause and assessment of risk factors for recurrence. What should physicians tell anxious parents about this frightening occurrence? Is prophylaxis with anticonvulsant agents appropriate? The authors address these questions and discuss the changing approach to management of febrile seizure. PMID- 1862045 TI - Thromboembolism prophylaxis. Choosing the proper method for surgical patients. AB - The primary care physician can play a major role in preoperative consultation in terms of assisting the surgical team to reduce the risk of thromboembolism. A preoperative risk assessment takes into account the type and duration of surgery as well as the existence of risk factors such as age and underlying medical conditions. With careful communication, the consulting physician and surgical team can together select a method of preventing thromboembolism that will prove both safe and effective. PMID- 1862046 TI - Drug-induced renal toxicity. Help in recognizing offending agents. AB - Drug-induced kidney disease is common, especially in hospitalized patients, and prompt recognition of the various nephrotoxic syndromes is important because many are reversible. Risk factors should be assessed before patients are given an agent that may cause acute renal failure (eg, nonsteroidal anti-inflammatory drug, aminoglycoside antibiotic, angiotensin-converting enzyme inhibitor, radiocontrast agent). Discontinuation of the responsible drug is often the only necessary therapy. PMID- 1862048 TI - There's no such thing as a free trip. PMID- 1862047 TI - Primary pulmonary hypertension. AB - Dyspnea is the most common symptom of primary pulmonary hypertension, an often fatal disease that has no apparent cause. Decreased cardiac output, congestive heart failure, and increased systemic venous pressure occur as the disease progresses. Use of oxygen therapy and vasodilators improves the prognosis in some patients. Those with little hope for long-term survival may benefit from heart and lung transplantation. PMID- 1862049 TI - Treatment of colonic diverticulitis. PMID- 1862050 TI - Dosage of ACE inhibitors. PMID- 1862051 TI - Ventricular arrhythmias. When should they be suppressed? AB - Patients with asymptomatic ventricular premature complexes who do not have evidence of heart disease should not be treated with either class I or class III (Vaughan Williams) antiarrhythmic drugs. Patients who are symptomatic may be given beta blockers. In patients who have heart disease, a number of risk factors may play a part, and the decision regarding therapy is more difficult. However, symptomatic patients with either sustained or nonsustained ventricular tachycardia must be treated with antiarrhythmic agents. In some patients, implantation of an automatic defibrillator may be necessary. PMID- 1862052 TI - Supraventricular tachycardia. Changes in management. AB - The various forms of supraventricular tachycardia can be differentiated by careful review of a patient's electrocardiogram. If reentrant tachycardia involves the atrioventricular node, intravenous adenosine (Adenocard) provides a rapid means of converting the tachycardia to sinus rhythm. Adverse effects of adenosine, though common, are mild and of brief duration. Wide QRS complex tachycardia of ventricular origin is usually not affected by the drug. PMID- 1862053 TI - Cardiovascular causes of syncope. Identifying and controlling trigger mechanisms. AB - Syncope usually has a cardiovascular source, so neurologic evaluation has a low diagnostic yield in these patients. Cardiac arrhythmias in persons with or without structural heart disease can produce syncope. Neurocardiogenic dysfunction that results in diminished venous return and hypercontractility is another frequent cause. Postural hypotension or left ventricular outflow obstruction may also be to blame. Careful history taking and physical examination, head-up tilt testing, echocardiography or radionuclide isotope imaging, and electrophysiologic study are often diagnostic. However, syncope remains undiagnosed in some patients, and they may require periodic reassessment. Treatment options are available for most cardiovascular disorders, among them use of pharmacologic agents; catheter, surgical, or radio-frequency modification of certain tachycardias; and permanent pacing. PMID- 1862054 TI - Urinary incontinence. Not a 'normal' part of aging. AB - Urinary incontinence is a common problem that affects millions of elderly men and women and their caregivers. Evaluation of incontinence is easy and inexpensive and does not require hospitalization. A basic evaluation consists of history taking (including a review of drug use), physical examination, and appropriate laboratory testing. Urodynamic evaluation may also be necessary. Treatment may consist of behavior modification techniques (eg, Kegel exercises, biofeedback, bladder retraining), use of a mechanical device or pharmacologic agent, or surgery. Should medical and surgical methods fail, alternatives are available to ensure patients' well-being and comfort. PMID- 1862055 TI - Herd immunity and the HIV epidemic. AB - Background. Herd immunity describes the collective immunocompetence of a population and its ability to resist disease. The diseases of mycobacteria, salmonella, hepatitis A, cryptosporidia, syphilis, measles, influenza, and numerous others recently have been seen in epidemic proportions in the United States. An association between these superimposed secondary infections and the human immunodeficiency virus (HIV) epidemic can be made since the HIV's imposition on individual immunity has ramifications on a population level through a decline in herd immunity. Conclusion. Exploring these epidemic phenomena as consequential to a reduction in herd immunity can provide a unifying hypothesis to explain existing and predict future infectious disease epidemic dynamics. The benefits of acting upon these implications has advantages for both the HIV infected and the uninfected. PMID- 1862057 TI - Screening mammography rates and barriers to use: a Los Angeles County survey. AB - The use of screening mammography among women 40 years of age and older in Los Angeles County was assessed through a random digit dial telephone interview. The sample of 802 women represents a large urban population with substantial proportions of blacks, Hispanics, and Asians. The survey obtained information regarding adherence to the ACS/NCI screening mammography guidelines, perceived benefits of early detection and mammography, perceived threat of developing breast cancer, and barriers to utilization. The results showed that 71% of the women had had at least one mammogram, with 49% having received a screening mammogram according to the guidelines for their age. Less than half the respondents knew the screening guidelines for their age, with women ages 40-49 years being less knowledgeable than women greater than or equal to 50 years old (29 vs 58% answering correctly). A logistic regression analysis predicting the likelihood of having obtained a screening mammogram according to the guidelines found the following to be predictive: concern over radiation (negative association), age (negative association), family history, knowledge of guidelines, and cost of a mammogram (negative association). Other demographic factors and beliefs were not significantly related to this dependent variable. PMID- 1862056 TI - Premenopausal determinants of menopausal estrogen use. AB - METHODS: Characteristics related to subsequent use of estrogen replacement therapy were evaluated prospectively in a cohort of 541 healthy premenopausal women being followed through the menopausal transition. RESULTS: Among women who became menopausal during the follow-up period, the most striking premenopausal baseline differences between menopausal estrogen users and never users were that users tended to be thinner and more likely to report past oral contraceptive use than never users (P less than or equal to 0.05). Nonsignificant trends were also observed, with menopausal estrogen users having higher total high-density lipoprotein cholesterol and lower fasting insulin prior to estrogen use than the menopausal never users (P less than or equal to 0.10). Weaker trends included greater alcohol intake and past week kilocalorie expenditure and lower blood pressure levels among menopausal estrogen users than never users. CONCLUSIONS: Although these findings do not preclude the probable protective effect of estrogen therapy on coronary heart disease morbidity and mortality, they do suggest that slightly healthier women may take menopausal hormones. PMID- 1862058 TI - A successful physician training program in cholesterol screening and management. AB - METHOD: Thirty-six resident physicians received a blood cholesterol training program which included training in blood cholesterol screening using a fingerstick method and a desktop analyzer, diet assessment and counseling, and a management protocol for follow-up diet and drug treatment. The program also included feedback to residents about their blood cholesterol screening activity, incentives, and biweekly articles in the department newsletter. RESULTS: Between 1986-1987 (baseline) and 1987-1988 (intervention), the percentage of the target patient population (ages 20-65 years, nonpregnant, not screened in the previous year) that was screened for hypercholesterolemia in this primary care practice increased from 16.2 to 23.2% [rate difference (RD) = 7.0; 95% confidence interval (CI) = 4.75-9.25]. The mean value of the screening tests decreased from 5.36 mmol/liter (207.2 mg/dl) to 5.08 mmol/liter (196.6 mg/dl; t = 2.98, P = 0.003) and the percentage of the population screened needing further evaluation decreased from 36.8 to 27.6% (RD 9.2; CI = 2.00-14.00). In the intervention year, compared with the baseline year, patients with a borderline blood cholesterol and cardiovascular risk factors were more likely to have a follow-up test (28.8% vs 11.9%, RD = 16.9; 95% CI = 0.80-33.00) and the low-density lipoprotein cholesterol test was used less for screening (8.2% vs 19.4%, P less than 0.0001). Conclusion. We conclude that this program was effectively integrated into a busy primary care practice, leading to improvement in blood cholesterol screening and management practices. PMID- 1862059 TI - A simple score and questionnaire to measure group changes in dietary fat intake. AB - BACKGROUND: A short 12-term questionnaire was designed to measure changes in the dietary intake of saturated and total fat among groups of people attending health promotion events. A simple score (the fat-habits score) derived from the questionnaire was compared with estimates of saturated and total fat intake (% total energy) estimated from a standard 180-item food frequency questionnaire of 105 children (less than 18 years) and 202 adults (greater than 18 years). RESULTS: The correlation coefficients for saturated fat intake and the fat-habits score were 0.60 (95% CI = 0.50 to 0.68) in adults and 0.54 (95% CI = 0.39 to 0.66) in children, and those for total fat and the fat-habits score were 0.46 (95% CI = 0.41 to 0.56) in adults and 0.40 (95% CI = 0.22 to 0.55) in children. Linear regression equations relating the fat-habits score to saturated and total fat were used to predict changes in fat intake in 12 children and 27 adults who completed both questionnaires 6 months apart. The differences between the predicted changes in saturated and total fat and the observed changes measured by the food frequency questionnaires were not significant (saturated fat: adults 0.3%, 95% CI = -1.3 to 0.7%; children -0.2%, 95% CI = -1.7 to 1.3%; total fat: adults -0.6%, 95% CI = -2.9 to 1.7%; children -0.4%, 95% CI = -2.8 to 2.0%). The study had a 90% power of detecting a difference between the predicted and the observed changes for saturated fat of greater than +/- 1.7% (adults) and +/- 2.5% (children), and for total fat of greater than +/- 3.9% (adults) and +/- 4.0% (children). Conclusion. Thus simple scores can be used to evaluate group changes in fat intake. PMID- 1862060 TI - Characteristics of participants in a televised smoking cessation intervention. AB - Participants in various components of a televised self-help smoking cessation program, based on the American Lung Association's Freedom From Smoking in 20 Days, are compared with a sample of the population of smokers to whom the intervention was addressed. Over 325,000 smokers in the target population were exposed to the program at some level. Most watched televised segments. Approximately 75,000 manuals were distributed and about 55,000 were used. Comparisons between participants and the targeted smoking population indicate that the intervention attracted those in the smoking population who are expected to be the majority of smokers by the Year 2000-blacks, females, and those with incomes under $13,000 per year. Participants with these characteristics were most likely to view the televised segments. Heavy smokers, females, and those with the most education were most likely to refer to the manual at least twice a week during the intervention. Older, nonblack participants and those with incomes of $13,000 or more per year were most likely to attend group support sessions outside the home. Overall, the patterns of association indicate that although a televised smoking cessation program can attract individuals similar to those projected to be smokers in 2000, participation in various components of the intervention will vary by demographic characteristics. PMID- 1862061 TI - Evaluation of a multicomponent group smoking cessation program. AB - BACKGROUND: Participants who had completed a multicomponent group smoking cessation program were interviewed to determine their smoking status and satisfaction with the program. METHODS: The follow-up interviews occurred an average of 20 months after entry to the program, with a response rate of 80% (89 out of 111 enrollees). Most individuals interviewed (82%) were able to quit for at least 24 hr; 25% were able to maintain nonsmoking status for 1 year or longer. RESULTS: Initial quit rates were comparable for both men and women, but women were more than twice as likely to have relapsed by the time of the follow-up interview. Participants rated self-monitoring as the most helpful of 10 program components, including nicotine fading, nicotine gum, group support, health information, and talks by ex-smokers. Ratings for the program overall were higher than the rating of any individual component. CONCLUSIONS: Since earlier studies have found that successful quitters use more coping strategies than relapsers, multicomponent programs offer participants an opportunity to learn a variety of techniques and choose the combination that works best for them. PMID- 1862062 TI - Preventing alcohol, marijuana, and cigarette use among adolescents: peer pressure resistance training versus establishing conservative norms. AB - BACKGROUND: Two strategies for preventing the onset of alcohol abuse, and marijuana and cigarette use were tested in junior high schools in Los Angeles and Orange Counties, California. The first strategy taught skills to refuse substance use offers. The second strategy corrected erroneous normative perceptions about prevalence and acceptability of use among peers and established conservative groups norms regarding use. METHODS: Four experimental conditions were created by randomly assigning schools to receive (a) neither of the experimental curricula (placebo comparison), (b) resistance skill training alone, (c) normative education alone, or (d) both resistance skill training and normative education. Students were pretested prior to the program and post-tested 1 year following delivery of the program. RESULTS: There were main effects of normative education for summary measures of alcohol (P = 0.0011), marijuana (P = 0.0096), and cigarette smoking (P = 0.0311). All individual dichotomous measures of alcohol, marijuana, and tobacco use indicated significant reductions in onset attributable to normative education. There were no significant main effects of resistance skill training. CONCLUSION: These results suggest that establishing conservative norms is an effective strategy for preventing substance use. PMID- 1862063 TI - Paradoxical effects of blood alcohol concentration charts. AB - BACKGROUND: This study was designed to determine the association between alcohol drinking and the possession of blood alcohol concentration charts. METHOD: A total of 30 college-age subjects participated in the study. Subjects were randomly assigned to either an experimental or a control group. All subjects answered a short entrance questionnaire to determine their height and weight. Those assigned to the experimental group were supplied a copy of a blood alcohol concentration chart and instructed in its use. The volume of alcoholic beverages consumed was surreptitiously counted for all subjects. Prior to leaving the premises the subjects completed an exit questionnaire which asked them to estimate the amount of alcohol they had consumed, whether they had driven to the pub, and whether they intended to drive away. The time spent in the pub was noted for each subject. RESULTS: Among those in the control group there was a tendency to overestimate the volume consumed, and for those in the experimental group, a tendency to more accurately estimate their consumption. Those given blood alcohol concentration charts consumed alcohol at a significantly higher rate than did those in the control group. CONCLUSION: A likely explanation for this outcome is that the chart served as a stimulus to prompt a drinker to more quickly achieve a blood alcohol level consistent with his/her drinking expectancies. PMID- 1862064 TI - A short history of occupational fitness and health promotion. AB - The suggestion of a linkage between adequate exercise and occupational health dates back to Ramazzini's classical observations on cobblers and tailors. However, excessive hours of work at too high an intensity were of greater concern than increase of fitness or health promotion in the early phases of the industrial revolution. Loss of physical condition is a more recent phenomenon, and it can be traced to automation in industry and the home, progressive urbanization, and widespread use of the automobile. The Canadian government has seen worksite fitness and health promotion programs as convenient tactics to reverse this trend. Exercise programs apparently yield a healthier and more effective labor force, and major corporations have thus followed the government's lead in developing fitness and health promotional facilities as a part of personnel or occupational health departments. Some health economists have suggested a substantial return upon such investment, but most corporations still regard the promotion of fitness and a healthy lifestyle as an expression of good citizenship. Currently, unifocal fitness programs are being replaced by modular health programs that address a wide range of lifestyle issues, including nutrition, stress relaxation, cigarette addiction, and drug abuse. The purpose of the present brief review is to trace from a personal perspective the development of an interest in employee fitness as an important component of occupational health programs over the past 300 years. The linkage of this phenomenon to the changing human demands of the worksite will also be explored. PMID- 1862065 TI - Pseudocysts in chronic pancreatitis: a morphological analysis of 57 resection specimens and 9 autopsy pancreata. AB - The pathology of chronic pancreatitis is reviewed in order to study the histology and incidence of pseudocysts in relation to the degree of pancreatic fibrosis and calcification. The series consisted of 57 resection specimens (49 partial pancreatectomy specimens and 8 total pancreatectomy specimens) and 9 autopsy pancreata. The histology of cystic lesions observed in the specimens was found to be identical to that of pseudocysts in acute pancreatitis. In 19 of 57, there was concomitant occurrence of focal autodigestive (fat) necrosis and pseudocysts. Pseudocysts were more common in specimens with focal fibrosis and few calcifications (13/25) than in those with diffuse advanced fibrosis and numerous calcifications (15/41). The findings indicate that sequelae of acute pancreatitis are frequently present in chronic pancreatitis, particularly in an early stage when fibrosis is still focal and calcification rare. This suggests that chronic pancreatitis may result from relapses of severe acute pancreatitis. A pathogenetic concept that relates acute pancreatitis with chronic pancreatitis is proposed. PMID- 1862066 TI - Human cytotoxic lymphocytes reactive with pancreatic adenocarcinoma cells. AB - In this study we describe the establishment of long-term cytotoxic T lymphocyte (CTL) cell lines and clones from lymph nodes of 9 pancreatic cancer patients by stimulation with allogeneic pancreatic tumor cell lines. The CTL cells exhibited strong cytolytic activity against many, but not all, allogeneic pancreatic tumor cell lines, but showed little or no reactivity against most nonpancreatic tumor cells, indicating they were detecting non-HLA antigens. Most of the cells from the established CTL cell lines were CD3+, and the CD8 antigen was also expressed on the majority of the cells. Occasional cultures exhibited a broad spectrum of cytolytic activity, and such CTL cell lines showed high expression of the natural killer (NK) cell markers, Leu-19 and Leu-11b. Seven clones were established from two CTL cell lines (LT and RE). These clones exhibited functional and phenotypic heterogeneity. The cytolytic activity of CTL cell lines and clones was inhibited by antibodies to CD3 antigen. Immunoprecipitation experiments using an anti-CD3 monoclonal antibody (Leu4) or anti-alpha/beta T cell receptor antibody (beta f1) revealed the presence of two bands of Mr 40,000 and Mr 50,000 in clones positive for the alpha/beta T cell receptor. The in vivo effects of the LT cytotoxic clones were studied in the Winn assay using pancreatic tumor xenografts in nude mice. Subcutaneous injections of a mixture of the cytotoxic clones and pancreatic tumor cells resulted in a complete inhibition of tumor development, whereas mice given injections of tumor cells and CTL clones that lacked cytotoxic activity against pancreatic cells developed tumors. PMID- 1862067 TI - Pancreatic release of pancreastatin in the pig. AB - It is known that pancreastatin-like immunoreactivity (PLI) occurs in the secretory granules of the islet B- and D-cells in the pig pancreas, and that porcine pancreastatin inhibits insulin secretion in rats and mice. In this study, we characterized the porcine plasma PLI and examined whether PLI is released from the pig pancreas in vivo. We found that PLI in unextracted pig plasma largely consists of two high-molecular fractions, with Mr values of 80-85,000 and 300 350,000, respectively. In addition, a small peak of PLI eluted after gel filtration at the position of synthetic porcine pancreastatin. After extraction on octadecylsilyl silica, virtually all PLI disappeared except in the fraction co eluting with porcine pancreastatin. In thiopenthal-anesthetized pigs, plasma samples were obtained from the carotid artery and the superior pancreaticoduodenal vein. By multiplying the venous-arterial concentration difference by the pancreatic venous plasma flow, a net pancreatic output of PLI of 420 +/- 120 pmol/min was found. This pancreatic PLI output was significantly reduced by electrical stimulation of the local autonomic nerves along the superior artery during atropine administration (p less than 0.001). Furthermore, the pancreatic venous PLI levels were elevated during intravenous infusion of glucose (p less than 0.01). We conclude that pig plasma PLI levels can be measured by radioimmunoassay after extraction on octadecylsilyl silica and that there is a net pancreatic output of PLI, which is reduced by sympathetic stimulation and enhanced during hyperglycemia. PMID- 1862068 TI - Effects of zinc and copper deficiency associated with protein or lipid deficiency on rat exocrine pancreatic secretion. AB - Copper and zinc are both secreted by the pancreas but are necessary for pancreatic secretion. We have studied the effects of a 4- or 8-week zinc or copper-deficient diet associated with or without lipid or protein deficiency on rat pancreatic secretion after stimulation by secretin, cerulein, or intraduodenal oleic acid. Twenty animals were in the control group; 40 rats were fed a copper-deficient diet (20 copper-deficient only and 20 copper- plus lipid deficient). Ninety rats were deprived of zinc (30 of zinc-deficient only, 30 zinc plus protein-deficient, 30 of zinc- plus lipid-deficient). Only the zinc- plus lipid-deficient diet for 8 weeks decreased basal bicarbonate and basal protein secretion (-42 and -70%, respectively, of the control values). Stimulated secretion was not markedly altered by copper deficiency while zinc deficiency, zinc plus protein deficiencies, and zinc plus lipid deficiencies suppressed almost responses to hormonal stimulation: After 8 weeks, the maximal protein response to oleic acid was reduced to 19.00 +/- 3.40, 18.58 +/- 3.00, and 12.04 +/- 2.91 microgram/30 min/g body weight in zinc- zinc and protein-; and zinc- and lipid-deficient diet, respectively, versus 39.87 +/- 6.33 microgram/30 min/g body weight (p less than 0.05) in controls. In all types of stimulation, lipid deficiency potentiated the deleterious effect of zinc deficiency on pancreatic secretion. This might be paralled with an extremely low level of lipid in the diet of people living in countries in which nutritional pancreatitis is observed and with the relative risk of developing an alcoholic chronic pancreatitis being increased by a low fat diet. PMID- 1862069 TI - Hormonal control of pancreatic secretion by intrajejunal HCl: studies in dogs with an autotransplanted entire jejunoileum. AB - To elucidate the role of hormones in the control of pancreatic secretion, we developed, in seven dogs, a model of total extrinsic denervation of the jejunoileum by autotransplanting this segment of bowel. A Thomas-like cannula was placed into the stomach, the duodenum (to collect pure pancreatic juice), and the proximal part of the jejunum. Thus, intestinal stimulants could only stimulate the pancreas via release of humoral (= hormonal) mediators. Seven control dogs received only the three fistulas. After recovery, dose-response curves of pancreatic bicarbonate and protein response to perfusion of the extrinsically denervated or innervated jejunoileum with HCl (1.5 to 48 mmol h-1) were performed with and without atropine (14 nmol kg-1 h-1 i.v.). Plasma levels of secretin were determined by radioimmunoassay. The maximal bicarbonate output occurred in response to 24 mmol h-1 of HCl and was significantly (p less than 0.05) higher in intact as compared to denervated animals. Atropine only significantly depressed the bicarbonate response to HCl in dogs with a denervated jejunoileum. HCl caused a dose-dependent increase in plasma levels of secretin, which was not altered by denervation and/or atropine. Irrespective of the innervation of the small bowel, pancreatic protein output was only significantly stimulated above basal when high loads (12-48 mmol h-1) of HCl were given. Atropine significantly reduced these responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1862070 TI - Venous bypass grafting for celiac occlusion in radical pancreaticoduodenectomy. AB - Radical pancreaticoduodenectomy was performed for cancer of the head of the pancreas in a 65-year-old male patient with congenital celiac occlusion. Preoperative angiography revealed that the arterial flow to the liver, spleen, and stomach was supplied via the pancreaticoduodenal arcade and that the dorsal pancreatic artery arose from the superior mesenteric artery. In order to perform radical pancreatectomy with sufficient clearance of lymph nodes and soft tissues around the pancreas, the celiac arterial circulation was reconstructed. The restoration of flow was effected via a saphenous vein graft between the common hepatic artery and the aorta. Postoperative angiography demonstrated patency of the graft. The patient's postoperative course was uneventful. PMID- 1862071 TI - Allosteric and catalytic binding of S-adenosylmethionine to Escherichia coli DNA adenine methyltransferase monitored by 3H NMR. AB - Adenine methylation of GATC sequences in DNA is carried out by the DNA adenine methyltransferase with the methyl group source being the cofactor S adenosylmethionine. We report 3H NMR studies on the interaction of DNA adenine methyltransferase with S-adenosylmethionine and the reaction when the ternary complex is formed with an oligonucleotide containing a GATC site. The methylation reaction was also studied in the presence of a competitive inhibitor and this showed two successive stages involved in the methylation and two sites of binding for S-adenosylmethionine. PMID- 1862072 TI - Expression of biologically active human corticosteroid binding globulin by insect cells: acquisition of function requires glycosylation and transport. AB - Human corticosteroid binding globulin (hCBG) is a 50- to 55-kDa serum glycoprotein that binds cortisol and progesterone with high affinity. To map the steroid-binding domain and to investigate the folding pathways of hCBG, we have established an expression system based on infection of insect cells with a recombinant baculovirus encoding hCBG. Infected Spodoptera frugiperda (Sf9) cells secrete immunoreactive hCBG at high levels (16-24 pmol per 10(6) cells per 40 h), and the recombinant protein binds cortisol with an affinity and specificity equivalent to that of human serum-derived hCBG. Thus, this system has the potential to provide large amounts of wild-type and mutant hCBGs for physical chemical analysis. Cotranslational asparagine-linked glycosylation is essential for acquisition of steroid-binding capability, as shown by the lack of cortisol binding activity of unglycosylated hCBG secreted in the presence of tunicamycin. Golgi-associated oligosaccharide processing, however, is not required for activity, as demonstrated by the endoglycosidase H susceptibility of the fully active, secreted glycoprotein. Comparison of the steroid-binding properties of intracellular and secreted hCBG with that synthesized in vitro in the rabbit reticulocyte lysate system suggests that this protein undergoes a maturation process during transport through the secretory pathway. This system will be useful for identifying the molecular determinants of biological function in hCBG. PMID- 1862073 TI - Theoretical studies on the dihydrofolate reductase mechanism: electronic polarization of bound substrates. AB - We have applied local density functional theory, an ab initio quantum mechanical method, to study the shift in the spatial electron density of the substrate dihydrofolate that accompanies binding to the enzyme dihydrofolate reductase. The results shed light on fundamental electronic effects due to the enzyme that may contribute to catalysis. In particular, the enzyme induces a long-range polarization of the substrate that perturbs its electron density distribution in a specific and selective way in the vicinity of the bond that is reduced by the enzyme. Examination of the electron density changes that occur in folate reveals that a similar effect is seen but this time specifically at the bond that is reduced in this substrate. This suggests that the polarization effect may be implicated in the reaction mechanism and may play a role in determining the sequence whereby the 7,8-bond in folate is reduced first, followed by reduction of the 5,6-bond in the resulting dihydro compound. PMID- 1862075 TI - Olfactory computation and object perception. AB - Animals that are primarily dependent on olfaction must obtain a description of the spatial location and the individual odor quality of environmental odor sources through olfaction alone. The variable nature of turbulent air flow makes such a remote sensing problem solvable if the animal can make use of the information conveyed by the fluctuation with time of the mixture of odor sources. Behavioral evidence suggests that such analysis takes place. An adaptive network can solve the essential problem, isolating the quality and intensity of the components within a mixture of several individual unknown odor sources. The network structure is an idealization of olfactory bulb circuitry. The dynamics of synapse change is essential to the computation. The synaptic variables themselves contain information needed by higher processing centers. The use of the same axons to convey intensity information and quality information requires time coding of information. Covariation defines an individual odor source (object), and this may have a parallel in vision. PMID- 1862074 TI - High density lipoprotein loses its effect to stimulate efflux of cholesterol from foam cells after oxidative modification. AB - In this study, we performed oxidative modification of high density lipoprotein (HDL) in vitro. The amount of lipid peroxide increased when either HDL2 or HDL3 was incubated with phosphate-buffered saline containing 5 microM CuSO4 for 24 h at 37 degrees C, indicating that both fractions of HDL were oxidatively modified. This modification resulted in denaturation of apolipoprotein AI on SDS/PAGE and increased the negative charge on agarose gel electrophoresis. When incubated with macrophage-derived foam cells, native HDL caused a marked efflux of cholesterol from them, leading to a decrease in the amount of cholesteryl ester in the cells. However, oxidized HDL showed a lessened effect on the decrease of cholesteryl ester in foam cells. These data suggest that oxidative modification of HDL may stimulate development of atherosclerosis by limiting efflux of cholesterol from foam cells. PMID- 1862076 TI - Rhodopsin mutations in autosomal dominant retinitis pigmentosa. AB - DNA samples from 161 unrelated patients with autosomal dominant retinitis pigmentosa were screened for point mutations in the rhodopsin gene by using the polymerase chain reaction and denaturing gradient gel electrophoresis. Thirty nine patients were found to carry 1 of 13 different point mutations at 12 amino acid positions. The presence or absence of the mutations correlated with the presence or absence of retinitis pigmentosa in 174 out of 179 individuals tested in 17 families. The mutations were absent from 118 control subjects with normal vision. PMID- 1862078 TI - v-abl causes hematopoietic disease distinct from that caused by bcr-abl. AB - v-abl, the oncogene transduced by Abelson murine leukemia virus, was first characterized by its ability to transform lymphoid cells. bcr-abl, the oncogene formed by a t(9;22) translocation thought to occur in human hematopoietic stem cells, is detectable in almost all cases of chronic myelogenous leukemia (CML), a malignancy of granulocytic cells. bcr-abl also causes a CML-like syndrome in mice whose bone-marrow cells are infected with a retrovirus transducing the gene. More recent reports have suggested that v-abl can, however, cause a disease similar to CML. We demonstrate here that v-abl, when transduced in a helper virus-containing system, causes disease similar to, but distinct from, the CML-like syndrome induced by bcr-abl. Animals whose bone marrow has been infected by v-abl virus develop modest splenomegaly, marked granulocytosis, and malignant disease of several hematopoietic cell types. Unlike animals with CML-like disease resulting from bcr-abl, the polymorphonuclear leukocytes from animals infected with a v-abl construct do not contain the v-abl provirus at a significant frequency. Histopathologic analysis also shows significant differences between the diseases caused by v-abl and bcr-abl. PMID- 1862077 TI - Error filtration, interference, and the human linkage map. AB - Typing error is a major problem in constructing human linkage maps, leading to incorrect orders and inflating map lengths. An error filter is incorporated into multiple pairwise analysis that corrects for inflation of map lengths and improves recovery of the correct order. Multipoint mapping is more sensitive to error, but when its output is adjusted for both error and interference, map lengths are no longer inflated in proportion to the number of loci and are close to those obtained by multiple pairwise analysis. PMID- 1862079 TI - Presence of activin (erythroid differentiation factor) in unfertilized eggs and blastulae of Xenopus laevis. AB - Activin A, a member of the transforming growth factor beta superfamily, has recently been found to have potent mesoderm-inducing activity on isolated early Xenopus animal-cap cells. We measured the activin activity of the Xenopus egg extract by using an erythroid-differentiating test with Friend leukemia cells. The results showed that an activin homologue is, indeed, contained in unfertilized eggs and blastulae of Xenopus laevis in a considerable amount. This activity was eluted at the same retention time as human activin A when fractionated by reversed-phase HPLC. Furthermore, the fraction containing erythroid-differentiating factor activity had mesoderm-inducing activity on Xenopus animal-cap cells. The mesoderm-inducing activity of this fraction was suppressed when coincubated with follistatin, an activin-binding protein. These results suggest that an endogenous activin may be a natural mesoderm-inducing factor acting in Xenopus embryogenesis. PMID- 1862080 TI - Adaptation of bird hemoglobins to high altitudes: demonstration of molecular mechanism by protein engineering. AB - Of two closely related species of geese, one, the greylag goose, lives in the Indian plains all year round, while the other, the bar-headed goose, lives at the Tibetan lakes and migrates across the Himalayas to winter in India. Another species, the Andean goose, lives in the High Andes all year round. Possession of a Hb with high oxygen affinity helps to adapt bar-headed and Andean geese to high altitudes. The Hb amino acid sequences of the bar-headed and the greylag geese differ by four substitutions, of which only one is unique among bird sequences: Pro-119 alpha (H2)----Ala. Perutz proposed that the two-carbon gap left by this substitution at the alpha 1 beta 1 contact raises the oxygen affinity, because it relaxes the tension in the deoxy or T structure [Perutz, M. F. (1983) Mol. Biol. Evol. 1, 1-28]. It was later found that the Hb of the Andean goose has a gap in the same position, due to the complementary substitution Leu-55 beta (D6)----Ser. We have tested Perutz's hypothesis by introducing each of these substitutions into human globin synthesized in Escherichia coli. The reconstituted Hbs combine cooperatively with oxygen. Their oxygen affinities exceed that of normal human Hb by an even larger factor than that found between the high-flying geese and the greylag goose. The mutant Hb Met-55 beta (D6)----Ser was crystallized. Its structure is the same as that of HbA, except in the immediate environment of the gap left by the substitution of the serine for the methionine side chain, which evidently causes the increased oxygen affinity of this Hb. PMID- 1862081 TI - Molecular cloning and expression in photosynthetic bacteria of a soybean cDNA coding for phytoene desaturase, an enzyme of the carotenoid biosynthesis pathway. AB - Carotenoids are orange, yellow, or red photo-protective pigments present in all plastids. The first carotenoid of the pathway is phytoene, a colorless compound that is converted into colored carotenoids through a series of desaturation reactions. Genes coding for carotenoid desaturases have been cloned from microbes but not from plants. We report the cloning of a cDNA for pds1, a soybean (Glycine max) gene that, based on a complementation assay using the photosynthetic bacterium Rhodobacter capsulatus, codes for an enzyme that catalyzes the two desaturation reactions that convert phytoene into zeta-carotene, a yellow carotenoid. The 2281-base-pair cDNA clone analyzed contains an open reading frame with the capacity to code for a 572-residue protein of predicted Mr 63,851. Alignment of the deduced Pds1 peptide sequence with the sequences of fungal and bacterial carotenoid desaturases revealed conservation of several amino acid residues, including a dinucleotide-binding motif that could mediate binding to FAD. The Pds1 protein is synthesized in vitro as a precursor that, upon import into isolated chloroplasts, is processed to a smaller mature form. Hybridization of the pds1 cDNA to genomic blots indicated that this gene is a member of a low copy-number gene family. One of these loci was genetically mapped using restriction fragment length polymorphisms between Glycine max and Glycine soja. We conclude that pds1 is a nuclear gene encoding a phytoene desaturase enzyme that, as its microbial counterparts, contains sequence motifs characteristic of flavoproteins. PMID- 1862082 TI - Monomeric erythrocyte band 3 protein transports anions. AB - The anion transport system of the human erythrocyte membrane was reconstituted in egg phosphatidylcholine membranes by using either the unmodified transport protein, band 3, or covalently crosslinked band 3 dimers. Unilamellar vesicles of a diameter of 32 +/- 3 nm were then isolated from the sample by passage through a French press and subsequent gel filtration. According to sedimentation equilibrium measurements, around 85% of the vesicles were devoid of protein. The remaining 15% contained either a single band 3 monomer or, when crosslinked band 3 protein was used, a single band 3 dimer. Vesicles containing either single monomers or single dimers showed a rapid, inhibitor-sensitive sulfate efflux, and the turnover numbers of band 3 for the inhibitor-sensitive flux component were identical in both systems. This shows that monomeric band 3 protein is able to transport anions and that dimerization of the protein does not change its transport activity. PMID- 1862083 TI - Reversed siderophores act as antimalarial agents. AB - We describe here a family of biomimetic iron carriers that display high binding efficiency for ferric ions and favorable permeation properties across erythrocytic membranes. These carriers inhibit in vitro growth of Plasmodium falciparum by scavenging intracellular iron. The chemical features were realized by reproducing the iron-binding cavities of natural iron carriers (siderophores) and by systematic substitutions of their hydrophilic envelopes for more hydrophobic ones. In contrast to natural carriers, which participate in receptor mediated iron uptake in cells and act as growth promoters, our synthetic carriers were designed to penetrate cellular membranes by diffusion, scavenge intracellular iron, and thereby act as growth inhibitors. Based on these properties we designate the compounds reversed siderophores and refer to the specific analogs of the natural ferrichrome as synthetic ferrichromes. The antimalarial activity of the synthetic ferrichromes correlated with their lipophilicity, and this antimalarial activity was averted when the chelators were applied as iron (III) complexes. The sites of synthetic ferrichrome action reside in the intraerythrocytic parasite and not in serum or on normal erythrocyte components. The agents were effective against all stages of parasite growth and against a variety of multidrug-resistant strains of P. falciparum. The most potent agent of this synthetic ferrichrome series, SF1-ileu, was not toxic to mammalian cells in culture and was 15-fold more potent and 20-fold faster acting than desferrioxamine. Taken in toto, these agents constitute a series of promising candidates for future use in malaria chemotherapy. PMID- 1862084 TI - Rat liver canalicular membrane vesicles contain an ATP-dependent bile acid transport system. AB - The secretion of bile by the liver is primarily determined by the ability of the hepatocyte to transport bile acids into the bile canaliculus. A carrier-mediated process for the transport of taurocholate, the major bile acid in humans and rats, was previously demonstrated in canalicular membrane vesicles from rat liver. This process is driven by an outside-positive membrane potential that is, however, insufficient to explain the large bile acid concentration gradient between the hepatocyte and bile. In this study, we describe an ATP-dependent transport system for taurocholate in inside-out canalicular membrane vesicles from rat liver. The transport system is saturable, temperature-dependent, osmotically sensitive, specifically requires ATP, and does not function in sinusoidal membrane vesicles and right side-out canalicular membrane vesicles. Transport was inhibited by other bile acids but not by substrates for the previously demonstrated ATP-dependent canalicular transport systems for organic cations or nonbile acid organic anions. Defects in ATP-dependent canalicular transport of bile acids may contribute to reduced bile secretion (cholestasis) in various developmental, inheritable, and acquired disorders. PMID- 1862085 TI - Evidence for nuclear targeting of prothymosin and parathymosin synthesized in situ. AB - To test the hypothesis that prothymosin and parathymosin contain amino acid sequences that cause them to be targeted to the cell nucleus, expression vectors were constructed containing a simian virus 40 promoter and cDNAs that would code for chimeric proteins composed of truncated human growth hormone (hGH) linked to the NH2 terminus of prothymosin or parathymosin. The truncated hGH lacked the signal peptide sequence required for its secretion. After transfection of these constructs into HeLa S3 cells, which do not normally synthesize hGH, the use of indirect immunofluorescence staining to follow the localization of the hGH chimeras demonstrated that both prothymosin and parathymosin caused targeting to the cell nucleus. Controls with a construct coding for native hGH only, and one coding for the truncated hGH lacking the signal peptide, revealed secretion into culture medium and staining in the endoplasmic reticulum and Golgi apparatus in the first case, and diffuse staining throughout the cytoplasm in the second. The results provide direct evidence, with proteins synthesized in situ, for the presence of nuclear localization signals in both prothymosin and parathymosin. PMID- 1862086 TI - Protein kinase C redistribution within CA3 stratum oriens during acquisition of nictitating membrane conditioning in the rabbit. AB - This manuscript describes experiments designed to investigate protein kinase C redistribution occurring during acquisition of the rabbit nictitating membrane (NM) conditioned response (CR). The first experiment defined the acquisition phase of the NM response for our laboratory. A group of rabbits (n = 6) was given 2 days of paired NM training; a second group (n = 6) was given 2 days of unpaired NM training. The data document a variable level of responding on day 1 for rabbits given paired training (mean +/- SEM, 21 +/- 11% CRs) but show that on day 2 most rabbits reached the behavioral asymptote (five of six rabbits responding with greater than 85% CRs). Rabbits responding at the behavioral asymptote were defined as having acquired the NM conditioned response. These data were interpreted to indicate that 1 day of training initiated processes necessary for behavioral acquisition (i.e., responding at the behavioral asymptote). A quantitative film autoradiographic study of [3H]phorbol 12,13-dibutyrate binding was then used to determine the distribution of hippocampal protein kinase C in rabbits sacrificed after receiving either 1 day of paired stimuli (n = 10), 1 day of unpaired stimuli (n = 6), or no stimuli (n = 6). Autoradiograms were analyzed by measuring binding in strictly defined regions of interest and from transept profiles. A significant increase in binding of the phorbol ester was found in the CA3 stratum oriens in the paired group relative to unpaired and naive controls. No other significant differences were found. PMID- 1862087 TI - Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis is an inexorably fatal disorder characterized by connective tissue deposition within the terminal air spaces resulting in loss of lung function and eventual respiratory failure. Previously, we demonstrated that foci of activated fibroblasts expressing high levels of fibronectin, procollagen, and smooth muscle actin and thus resembling those found in healing wounds are responsible for the connective tissue deposition and scarring in idiopathic pulmonary fibrosis. Using in situ hybridization and immunohistochemistry, we now demonstrate the presence of transforming growth factor beta 1 (TGF-beta 1), a potent profibrotic cytokine, in the foci containing these activated fibroblasts. These results suggest that matrix-associated TGF-beta 1 may serve as a stimulus for the persistent expression of connective tissue genes. One potential source of the TGF-beta 1 is the alveolar macrophage, and we demonstrate the expression of abundant TGF-beta 1 mRNA in alveolar macrophages in lung tissue from patients with idiopathic pulmonary fibrosis. PMID- 1862088 TI - Cholinesterase-like domains in enzymes and structural proteins: functional and evolutionary relationships and identification of a catalytically essential aspartic acid. AB - Primary sequences of cholinesterases and related proteins have been systematically compared. The cholinesterase-like domain of these proteins, about 500 amino acids, may fulfill a catalytic and a structural function. We identified an aspartic acid residue that is conserved among esterases and lipases (Asp-397 in Torpedo acetylcholinesterase) but that had not been considered to be involved in the catalytic mechanism. Site-directed mutagenesis demonstrated that this residue is necessary for activity. Analysis of evolutionary relationships shows that the noncatalytic members of the family do not constitute a separate subgroup, suggesting that loss of catalytic activity occurred independently on several occasions, probably from bifunctional molecules. Cholinesterases may thus be involved in cell-cell interactions in addition to the hydrolysis of acetylcholine. This would explain their specific expression in well-defined territories during embryogenesis before the formation of cholinergic synapses and their presence in noncholinergic tissues. PMID- 1862089 TI - Preferential integration of marker DNA into the chromosomal fragile site at 3p14: an approach to cloning fragile sites. AB - Fragile sites are specific regions of chromosomes that are prone to breakage. In cells cultured under conditions that induce fragile site expression, high levels of inter- and intrachromosomal recombination have been observed involving chromosomal bands containing fragile sites. To determine whether expression of specific fragile sites would facilitate preferential integration of exogenous DNA at these recombination hot spots, the vector pSV2Neo was transfected into a Chinese hamster-human somatic cell hybrid containing a derivative chromosome 3 as its only human component. Chromosome 3 contains a common fragile site at band 3p14.2 (FRA3B) that is induced by aphidicolin. Both cells induced to express FRA3B and the uninduced control cells were transfected with the pSV2Neo selectable plasmid. In situ hybridization of a biotin-labeled pSV2Neo probe to metaphase chromosomes revealed one to three integration sites in each stably transfected clone. Four of 13 clones transfected under conditions of FRA3B induction showed integration of pSV2Neo at 3p14; these clones also showed specific integration into hamster chromosome 1 and a rearranged chromosome characteristic of CHO cells (mar2). The 7 control clones, however, showed an apparently random pattern of pSV2Neo integration. Significant hybridization of pSV2Neo to both FRA3B and Chinese hamster chromosomes 1 and mar2 was seen in 100 cells from pooled colonies transfected after treatment with aphidicolin. These results suggest that preferential integration of marker DNA into human and Chinese hamster fragile sites occurs with exposure to aphidicolin. The nature of the DNA sequences at fragile sites is unknown and, despite a number of approaches, these sequences have not yet been isolated; our procedure may represent an approach to the cloning of fragile sites. PMID- 1862090 TI - Correlation between retinoblastoma gene expression and differentiation in human testicular tumors. AB - Inactivation of the retinoblastoma gene (RB gene) is associated with the development of several human malignancies including retinoblastomas, some osteo- and soft tissue sarcomas, small cell lung cancer, and possibly breast and bladder cancers. To our knowledge, this gene has not been evaluated in human germ-cell malignancies. In this study 67 primary testicular germ-cell tumors and 4 testicular non-germ-cell malignancies were examined to determine the prevalence and nature of RB gene alterations. Decreased expression of RB gene mRNA was found in all testicular germ-cell tumors (both seminomas and nonseminomas) examined. The RB protein could not be detected by immunohistochemical analysis in the undifferentiated cells of any germ-cell tumors whereas the differentiated malignant cells present in 14/15 teratocarcinomas expressed the protein. No gross alterations of the RB gene were found at DNA level in any of the examined specimens. This and the presence of the RB protein in the more differentiated tumor cells of teratocarcinomas suggest that changes in transcript levels rather than mutation(s) of the gene may be responsible for the absent or decreased RB expression in human germ-cell tumors. To date studies on the mechanism of RB regulation have demonstrated that it occurs at the protein level by phosphorylation of the p105 gene product. The findings presented here indicate that additional regulation might occur at the transcript level. PMID- 1862091 TI - Nucleotide polymorphism and evolution in the glyceraldehyde-3-phosphate dehydrogenase gene (gapA) in natural populations of Salmonella and Escherichia coli. AB - Nucleotide sequences of the gapA gene, encoding the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, were determined for 16 strains of Salmonella and 13 strains of Escherichia coli recovered from natural populations. Pairs of sequences from strains representing the eight serovar groups of Salmonella differed, on average, at 3.8% of nucleotide sites and 1.1% of inferred amino acids, and comparable values for E. coli were an order of magnitude smaller (0.2% and 0.1%, respectively). The rate of substitution at synonymous sites was significantly higher for codons specifying the catalytic domain of the enzyme than for those encoding the NAD(+)-binding domain, but the nonsynonymous substitution rate showed the opposite relationship. For Salmonella, statistical tests for nonrandom clustering of polymorphic sites failed to provide evidence that intragenic recombination or gene conversion has contributed to the generation of allelic diversity. The topology of a tree constructed from the gapA sequences was generally similar to that of phylogenetic trees of the strains based on multilocus enzyme electrophoresis, but the level of divergence of gapA in Salmonella group V from other Salmonella and E. coli strains is much greater than that indicated by DNA hybridization for the genome as a whole. PMID- 1862092 TI - Origin of a "bridge" intron in the gene for a two-domain globin. AB - Red cells of the clam Barbatia reeveana express two hemoglobins, one composed of 16- to 17-kDa chains and the other of 35-kDa chains. The nucleotide sequence of the cDNA encoding the 35-kDa chain shows that the polypeptide has two very similar heme-binding domains, which are joined without use of an additional bridging sequence. Two novel introns occur in the gene for the two-domain globin: one, the "precoding" intron, is located two bases 5' from the start codon, and the other, a "bridge" intron, separates the DNA sequences encoding the two domains. Close correspondence exists between the 3' end of the precoding intron and the 3' end of the bridge intron and between parts of the 3' noncoding region of the cDNA for the two-domain globin and the 5' end of the bridge intron. These observations indicate that the bridge intron arose by unequal crossing-over between two identical or very similar genes for a single-domain globin. This conclusion, together with the proposal that exons were initially independent "minigenes" [Gilbert, W. (1987) Cold Spring Harbor Symp. Quant. Biol. 52, 901 905], suggests that many introns may have evolved from the 5' noncoding region of one gene and/or the 3' noncoding region of a second gene. This hypothesis implies that splice junctions would be associated with the original NH2 and COOH termini of proteins and provides an explanation for the observation that splice junctions usually map to protein surfaces. They do so because most NH2- and COOH-terminal residues are usually located on or near the surfaces of proteins. PMID- 1862093 TI - Identification of prolactin and growth hormone binding proteins in rabbit milk. AB - Two distinct soluble proteins that specifically bind 125I-labeled human growth hormone (GH) are identified in the supernatant of ultracentrifuged rabbit milk, using HPLC gel filtration. The higher molecular weight proteins is GH specific, whereas the other one is specific for prolactin (PRL). The PRL-binding protein has a very high affinity for the hormone, almost 10 times higher than the affinity of the mammary gland membrane receptor. The PRL-binding protein is immunoprecipitated by a monoclonal antibody against the PRL receptor; another monoclonal antibody, which inhibits the PRL binding to mammary gland membranes, is a poor competitor for the PRL binding to the milk protein. These findings suggest that the milk PRL-binding protein corresponds to the binding domain of the receptor, but also that the conformation of the receptor and of the binding protein might differ. The milk and the plasma GH-binding proteins have a similar binding affinity. In cross-linking experiments using 125I-labeled human GH, the Mr of the GH-binding protein and of the PRL-binding protein were estimated to be 51,000 and 33,000, respectively. The binding proteins identified in the present work are probably responsible for the transport of their specific ligands in the milk. It is also conceivable that they have a role in the effects of GH and PRL in the mammary gland and/or the intestine of the young. PMID- 1862094 TI - Photoinduced degradation of the D1 polypeptide in isolated reaction centers of photosystem II: evidence for an autoproteolytic process triggered by the oxidizing side of the photosystem. AB - When the isolated D1/D2/cytochrome b559 complex was exposed to bright light, a distinctive pattern of D1 polypeptide fragments was observed under both aerobic and anaerobic conditions. The major degradation product had an apparent molecular mass of 24 kDa, while other fragments were detected at 17, 14, and 10 kDa by immunoblotting. This pattern was observed when the electron acceptors 2,5-dibromo 3-methyl-6-isopropyl-p-benzoquinone or silicomolybdate were present during illumination. It is known that these conditions stabilize P680+ chlorophyll and bring about the photooxidation and destruction of pigments in the reaction center, particularly chlorophyll absorbing at 670 nm and beta-carotene. When P680+ was not allowed to accumulate, either by omission of an electron acceptor or by addition of both an electron donor (Mn2+) and an acceptor, no breakdown fragments were observed. In the former case, however, some degradation of the D1 and D2 polypeptides did occur. Under conditions that gave rise to the characteristic D1 breakdown pattern, the D2 polypeptide was also degraded to specific fragments detected at about 29 and 21 kDa by immunoblotting. The results indicate that the photoinduced degradation of D1 (and D2) does not involve exogenous proteases but is most likely an autoproteolytic process. Moreover, our data indicate that the photochemical damage giving rise to D1 and D2 degradation occurs on the oxidizing rather than the reducing side of photosystem II and involves photooxidation of the accessory pigments. The results are discussed in terms of D1 and D2 turnover and photoinhibition. PMID- 1862096 TI - Role of diversifying selection and gene conversion in evolution of major histocompatibility complex loci. AB - Genes at the major histocompatibility complex (MHC) in mammals are known to have exceptionally high polymorphism and linkage disequilibrium. In addition, these genes form highly complicated gene families that have evolved through gene conversion and unequal crossing-over. It has been shown recently that amino acid substitution at the antigen recognition site (ARS) is more rapid than synonymous substitution, suggesting some kind of positive natural selection working at the ARS. It is highly desirable to know the interactive effect of gene conversion and natural selection on the evolution and variation of MHC gene families. A population genetic model is constructed that incorporates both selection and gene conversion. Diversifying selection is assumed in which sequence diversity is enhanced not only between alleles at the same locus but also between duplicated genes. Expressed and nonexpressed loci are assumed as in the class I gene family of MHC, with gene conversion occurring among all loci. Extensive simulation studies reveal that very weak selection at individual amino acid sites in combination with gene conversion can explain the unusual pattern of evolution and polymorphisms. Here both gene conversion and natural selection contribute to enhancing polymorphism. PMID- 1862095 TI - Sequestration of basic fibroblast growth factor in the primate retinal interphotoreceptor matrix. AB - The interphotoreceptor matrix (IPM) occupies the extracellular space between the photoreceptors of the retina and the apical surface of the retinal pigmented epithelium. A large proportion of the IPM is composed of aqueous-insoluble glycoconjugates, including chondroitin sulfate-containing proteoglycans, the distribution of which exhibits both apical-basal and photoreceptor cell type specific heterogeneities. The precise function of most insoluble IPM constituents is unknown, although the available evidence suggests some may contribute to retinal adhesion or photoreceptor survival. We have now identified basic fibroblast growth factor (bFGF), or an immunologically related protein from the FGF family, within the IPM. The IPM is labeled on sections of primate retinas by a battery of polyclonal antibodies (Abs) directed against various peptide sequences of bFGF and by an Ab to bovine brain bFGF. bFGF Abs also bind to purified preparations of aqueous-insoluble IPM. All bFGF Abs utilized cross-react with equivalent low molecular mass components of 16.5-17.5 kDa on Western blots of insoluble IPM proteins, purified bFGF, and recombinant bFGF. The Abs do not bind any aqueous-soluble IPM components, suggesting that the bFGF is normally bound to an insoluble IPM constituent(s) in situ. The fact that bFGF is sequestered in the IPM and is located in such close proximity to the photoreceptors, the retinal pigmented epithelium, and Mueller's glia raises the strong possibility that it is synthesized by and regulates the activities of one or more of these three cell types in vivo. PMID- 1862097 TI - Expression of an antisense viral gene in transgenic tobacco confers resistance to the DNA virus tomato golden mosaic virus. AB - Transgenic tobacco plants carrying a genetic cassette including an antisense DNA sequence of the virally encoded AL1 gene of the geminivirus tomato golden mosaic virus (TGMV) were constructed; AL1 encodes a protein absolutely required for TGMV DNA replication. These genetic cassettes also contained, on the same transcription unit, a gene encoding hygromycin resistance, which allowed selection for concomitant expression of the antisense gene. In transgenic lines, RNA transcripts of the predicted size and strand specificity were detected in antisense plants and sense controls. After infection of plants with TGMV, by agroinoculation, the frequency of symptom development was very significantly reduced in a number of antisense lines and correlated, broadly, with the abundance of antisense RNA transcript and with a reduction in viral DNA harvested from infected leaf tissue. We used an in vitro assay to study viral DNA replication in the absence of cell-to-cell spread; no replication was seen in five of the six antisense lines studied, in contrast to controls. PMID- 1862098 TI - Proximity measurements between H-2 antigens and the insulin receptor by fluorescence energy transfer: evidence that a close association does not influence insulin binding. AB - Reports based on coprecipitation experiments have suggested that major histocompatibility complex class I products are complexed with the insulin receptor on the cell surface. Using an independent method that avoids the creation of immunoprecipitation artifacts during membrane solubilization, we have studied insulin receptor-class I product associations by determining the proximity between these class I products and the insulin receptor on intact cells with the use of fluorescence energy transfer. Significant energy transfer was seen between the insulin receptor and both murine H-2K- as well as H-2D-end products, indicating close proximity (e.g., within 10 nm). This cell-surface association is not from the relatively high class I density in that no significant energy transfer was measured between H-2K- vs. H-2D-end proteins. To extend these observations, we also tested whether class I products influence insulin-receptor binding and postbinding events as a result of their physical association. Using related cell lines positive and negative for class I expression, we found no correlation between insulin-receptor density or binding affinity with H-2 product expression. The class I-null variant, however, demonstrated an increase in insulin-mediated insulin-receptor internalization to suggest that if major histocompatibility complex class I products directly affect insulin-receptor function through specific cell-surface interactions, they may do so after ligand binding. PMID- 1862099 TI - Rapid medium perfusion rate significantly increases the productivity and longevity of human bone marrow cultures. AB - Long-term in vitro human hematopoietic (Dexter) cultures are limited both in their longevity (8-12 weeks) and in their cell production over time. Hematopoiesis in vivo continues unabated throughout life, suggesting that failure to obtain continuous hematopoiesis in vitro is probably due to the failure of culture conditions to accurately reproduce the in vivo state. Since bone marrow cells in vivo exist at high density and are rapidly perfused by plasma components, we examined the effects of the culture medium perfusion rate and inoculum density on longevity and productivity of human bone marrow cultures. Culture efficiency and longevity were relatively independent of the variation in inoculum density from 10(6) to 5 x 10(6) cells per ml but were significantly altered by the medium perfusion rate. Increased culture perfusion was superior to traditional Dexter schedules, with 0.5 medium volume exchange per day (3.5 volume per week) being optimal. The cultures under these conditions demonstrated an increasing rate of cell production from weeks 4 to 10, with the cell production rate doubling approximately every 2 weeks. Following weeks 10-12 in culture, the cell production rate of all cultures decayed. Production of nonadherent progenitor cells was also highest in cultures perfused at 3.5 medium volume exchanges per week, where progenitor cell production was stable from weeks 6 to 18. The nonadherent cells collected were predominantly macrophages by week 19, except for the cultures perfused at a rate of 3.5 volumes per week and seeded at 5 x 10(6) cells per ml, in which production of granulocytes remained high through week 19. Establishment of more optimal perfusion conditions supports the continuous stable generation of progenitor cells over 5 months in culture, suggesting that primitive stem cells are surviving and proliferating in these cultures. PMID- 1862101 TI - Maternal inheritance of centrosomes in mammals? Studies on parthenogenesis and polyspermy in mice. AB - The centrosome, the microtubule-organizing center of the cell, is introduced typically by the sperm at fertilization. In some mammals, however, this paternal pattern of inheritance appears to be violated. The hypothesis that the centrosome is maternally inherited was tested during parthenogenesis, polyspermy, and polygyny as well as after recovery from microtubule inhibition at first mitosis. During parthenogenesis the paternal contribution was absent, and in polyspermy the paternal contribution was multiplied. Haploid and diploid parthenogenotes as well as polyspermic and digynic fertilized eggs each segregated their centrosomes to organize a bipolar mitotic apparatus. Oocytes recovering from a nocodazole block formed two normal bipolar mitotic apparatus; the paternal chromosomes aligned at one spindle equator, while the maternal chromosomes were found at the other. These results show that the centrosome is maternally inherited from cytoplasmic sites in the mouse. The evolutionary switch from paternal to maternal inheritance in mammals might be related to the additional dangers that parthenogenesis represents: a threat to the life of the mother as well as to the life of the fetus. PMID- 1862100 TI - Coincidence cloning of Alu PCR products. AB - Coincidence cloning allows the isolation of sequences held in common by two genomic DNA populations. Human DNA from two human-hamster hybrid cell lines was amplified by Alu-repeat primers (Alu PCR) and the products originating from the shared human chromosomal region were cloned. To achieve this, human sequences were amplified with very similar Alu primers from the two different human-hamster hybrid cell lines. The products were then digested with an appropriate restriction enzyme (either BamHI or Sal I), combined, denatured, and reannealed. The derived heteroduplex molecules (originating from the human regions common to both cell lines) had single BamHI and Sal I cohesive ends due to the primers used, so that they could be cloned in a double-digested plasmid vector. We used this method to enrich about 10-fold for Alu PCR products from the human chromosome 19q13.2 region, resulting in a region-specific clone collection. About 90% of the recombinants with BamHI-Sal I inserts are derived from the common region. This approach allows the boundaries for the regional probe isolation to be defined by combinations of hybrids rather than single hybrid cell lines, thus permitting greater flexibility in the selection of regions for probe isolation. PMID- 1862103 TI - Prediction of optimal peptide mixtures to induce broadly neutralizing antibodies to human immunodeficiency virus type 1. AB - Sequences of the principal neutralizing determinant (PND) of the external envelope protein, gp120, from 245 isolates of human immunodeficiency virus type 1 are analyzed. The minimal set of peptides that would elicit antibodies to neutralize a majority of U.S. and European isolates of human immunodeficiency virus type 1 is determined with the assumption that peptides of a given length including the central Gly-Pro-Gly triad are required. In spite of the hypervariability of the PND, 90% of these 245 sequences include peptides from a set of 7 pentapeptides, 13 hexapeptides, or 17 heptapeptides. Tests of these peptide sets on 78 additional PND sequences show that 95% are covered by the 7 pentapeptides, 94% by the 13 hexapeptides, and 86% by the 17 heptapeptides. To anticipate variants not yet observed, single amino acid mutation frequencies from the 245 isolates are used to calculate an expanded set of the 10,000 most probable PND sequences. These sequences cover 86% of the total distribution expected for the central portion of the PND. Peptide lists derived from this expanded set when tested on the 78 additional sequences show that 7 pentapeptides cover 95%, 13 hexapeptides cover 94%, and 17 heptapeptides cover 94%. These results suggest that peptide cocktails of limited size with the potential to cover a large fraction of PND sequence variation may be feasible vaccine candidates. PMID- 1862102 TI - Refractoriness to growth hormone is associated with increased intracellular calcium in rat adipocytes. AB - In adipocytes that have been deprived of growth hormone (GH) for at least 3 hr, GH elicits a transient insulin-like response that is followed by a period of refractoriness to further insulin-like stimulation. Exposure of adipocytes to GH in the first hour of a 3-hr incubation prevents the appearance of insulin-like sensitivity. Intracellular Ca2+ concentration [( Ca2+]i) was measured in individual adipocytes that were loaded with fura-2 hexakis(acetoxymethyl) ester after preincubation in the presence (refractory) or absence (sensitive) of recombinant human GH at 100 ng/ml. Using a dual nitrogen laser imaging microscope with computer-assisted image processing to measure fluorescence changes, we observed that resting [Ca2+]i was 220 +/- 10 nM in refractory adipocytes and 110 +/- 6 nM in sensitive adipocytes (P less than 0.001). GH had no acute effect on [Ca2+]i in sensitive adipocytes but caused a sustained 3-fold increase in [Ca2+]i in refractory cells within 3 min (P less than 0.001). Insulin did not change [Ca2+]i in either sensitive or refractory adipocytes. In refractory cells treated with insulin and GH simultaneously, insulin completely blocked the rise in [Ca2+]i due to GH. Oxytocin elicited a prompt increase in [Ca2+]i followed by a quick return to resting levels in both sensitive and refractory cells. These findings indicate that basal [Ca2+]i is increased in refractory cells and that GH produces a sustained rise in [Ca2+]i only in refractory adipocytes. We suggest that the sustained increase in [Ca2+]i produced by GH in refractory cells prevents the expression of the insulin-like response. PMID- 1862104 TI - Dissociation of thermoregulation in cats with cytotoxic pontine lesions. AB - Neurons of the pontine tegmentum of the cat were lesioned by microinjection of ibotenic acid into the brainstem. The threshold ambient temperatures for heat gain (shivering) and for heat-loss (panting) responses, together with brain and skin temperatures, were measured in intact animals and after the neurotoxic lesioning. After the lesioning the shivering threshold was altered but the panting threshold did not change. The results indicate that certain neurons involved in the shivering response reside in the pontine tegmentum. Neurons involved in the panting response, however, may lie outside the lesioned areas. PMID- 1862106 TI - The C-terminal half of UvrC protein is sufficient to reconstitute (A)BC excinuclease. AB - The UvrC protein is one of three subunits of the Escherichia coli repair enzyme (A)BC excinuclease. This subunit is thought to have at least one of the active sites for nucleophilic attack on the phosphodiester bonds of damaged DNA. To localize the active site, mutant UvrC proteins were constructed by linker scanning and deletion mutagenesis. In vivo studies revealed that the C-terminal 314 amino acids of the 610-amino acid UvrC protein were sufficient to confer UV resistance to cells lacking the uvrC gene. The portion of the uvrC gene encoding the C-terminal half of the protein was fused to the 3' end of the E. coli malE gene (which encodes maltose binding protein), and the fusion protein MBP-C314C was purified and characterized. The fusion protein, in combination with UvrA and UvrB subunits, reconstituted the excinuclease activity that incised the eighth phosphodiester bond 5' and the fourth phosphodiester bond 3' to a psoralen thymine adduct. These results suggest that the C-terminal 314 amino acids of UvrC constitute a functional domain capable of interacting with the UvrB-damaged DNA complex and of inducing the two phosphodiester bond incisions characteristic of (A)BC excinuclease. PMID- 1862105 TI - Neuronal activity up-regulates astroglial gene expression. AB - Neuronal gene expression is known to be modulated by functional activity. This modulation is thought to play a key role in determining the differentiation of developing neurons and regulating the operation of mature neurons. Here we describe a regulation of astroglial gene expression by neuronal activity. We report that intense neuronal activity (electrically induced seizures) in rat hippocampus leads to rapid and dramatic increases in mRNA for glial fibrillary acidic protein (GFAP), an astroglia-specific intermediate filament protein. GFAP mRNA levels increased at sites of stimulation as well as in areas that were synaptically activated by the resultant seizures. When seizures were induced repetitively for many days, levels of GFAP mRNA remained chronically elevated. However, GFAP mRNA returned to control levels within a few days after the cessation of stimulation. The coupling between astroglial gene expression and neuronal activity may be a mechanism through which neuronal activity modulates the function of supporting cells that are responsible for regulating the extracellular microenvironment of the brain. PMID- 1862108 TI - Human cells contain protein specifically binding to a single 1,N6-ethenoadenine in a DNA fragment. AB - A human DNA binding protein has been characterized from cell-free extracts of liver, placenta, and cultured cells. This protein, apparent molecular mass approximately 35 kDa, to our knowledge, does not resemble other proteins reported to bind to carcinogen-modified DNA. The probe used for characterization was a 25 base oligonucleotide containing a single site-specifically placed 1,N6 ethenoadenine (epsilon A), a product of vinyl chloride metabolism. When annealed to form an epsilon A.T or epsilon A.C pair, a strong affinity to the protein was observed, with a binding constant of approximately 1 x 10(9) M-1. In contrast, very little binding was found with an epsilon A.A pair and none was found with an epsilon A.G pair. This suggests protein recognition of a specific structural alteration. Other defined probes with alkyl adducts did not bind. In addition, the human cell extracts and a rat liver extract were found to nick specifically at the 5' side of the epsilon A adduct, which could indicate a possible associated repair activity. PMID- 1862107 TI - Isolation and functional expression of a mammalian prohormone processing enzyme, murine prohormone convertase 1. AB - We have combined gene cloning with an assay for prohormone biosynthesis and processing in Xenopus oocytes to identify the genes that encode mammalian prohormone processing enzymes. The coinjection of RNA encoding murine prohormone convertase 1 (mPC1), a mammalian endoprotease, along with proopiomelanocortin RNA into an oocyte results in the appropriate cleavage after paired basic residues in the proopiomelanocortin polyprotein necessary to generate corticotropin. The ability of mPC1 to generate corticotropin, along with the observation that mPC1 is specifically expressed in endocrine and neuronal cells, suggests that the mPC1 gene encodes the endopeptidase responsible for the pathway of proopiomelanocortin cleavage observed in the anterior pituitary. PMID- 1862109 TI - Clonality in myeloproliferative disorders: analysis by means of the polymerase chain reaction. AB - The myeloproliferative syndromes are acquired disorders of hematopoiesis that provide insights into the transition from somatic cell mutation to neoplasia. The clonal origin of specific blood cells can be assessed in patients with X chromosome-linked polymorphisms, taking advantage of random inactivation of the X chromosome. We have adapted the PCR for determination of clonality on as few as 100 cells, including individual colonies grown in culture. Amplifying a polymorphic portion of the X chromosome-linked phosphoglycerate kinase (PGK) gene after selective digestion of the active X chromosome with a methylation-sensitive restriction enzyme gave results fully concordant with standard Southern blotting of DNA samples from normal (polyclonal) polymorphonuclear cells (PMN) as well as clonal PMN from patients with myelodysplastic syndrome and polycythemia vera (PCV). We have used this technique to demonstrate heterogeneity of lineage involvement in patients with PCV. The same clinical phenotype may arise from clonal proliferation of different hematopoietic progenitors. PMID- 1862110 TI - Interpulse interval in circulating growth hormone patterns regulates sexually dimorphic expression of hepatic cytochrome P450. AB - Plasma growth hormone (GH) profiles are sexually differentiated in many species and regulate the sex-dependence of peripubescent growth rates and liver function, including steroid hydroxylase cytochrome P450 expression, by mechanisms that are poorly understood. By use of an external pump to deliver to hypophysectomized rats pulses of rat GH of varying frequency and amplitude, a critical element for liver discrimination between male and female GH patterns was identified. Liver expression of the male-specific steroid 2 alpha (or 16 alpha)-hydroxylase P450, designated CYP2C11, was stimulated by GH at both physiological and nonphysiological pulse amplitudes, durations, and frequencies, provided that an interpulse interval of no detectable GH was maintained for at least 2.5 hr. This finding suggests that hepatocytes undergo an obligatory recovery period after stimulation by a GH pulse. This period may be required to reset a GH-activated intracellular signaling pathway or may relate to the short-term absence of GH receptors at the hepatocyte surface after a cycle of GH binding and receptor internalization. These requirements were distinguished from those necessary for the stimulation by GH of normal male growth rates in hypophysectomized rats, indicating that different GH responses and, perhaps, different GH-responsive tissues recognize distinct signaling elements in the sexually dimorphic patterns of circulating GH. PMID- 1862113 TI - [A look at home nursing care]. PMID- 1862112 TI - Allografts of tumor nuclear transplantation embryos: differentiation competence. AB - The developmental potential of nuclei can be studied by nuclear transplantation. Although amphibian blastula nuclei and other early embryonic nuclei are totipotent, to our knowledge no nucleus from an adult cell has ever been shown to be totipotent by this procedure. Transfer of Lucke renal carcinoma nuclei into enucleated eggs results in prefeeding swimming tadpoles. Inasmuch as these tadpoles die, rescue of this pluripotential tissue was attempted by grafting fragments of triploid tumor nuclear transplant tadpoles to the tails of normal diploid Rana pipiens hosts. Grafts of tumor nuclear transplant tadpole tissue were histologically indistinguishable from grafts of normally fertilized embryos and developed normal-appearing structures such as complete eyes, well differentiated neural tissues, kidney tubules, and gut epithelium. Moreover, histological differentiation in tumor nuclear transplant grafts was comparable to that observed in 50-day-old normal larvae. Grafting enhanced the survival of tumor nuclear transplant tissue from no more than 14 days as part of the donor tadpole to 40 days at which time the grafts were harvested as healthy tissue. Thus, both differentiation and survival of tumor nuclear transplant tissue were augmented with the grafting procedure. Cytophotometric analysis of ploidy was used to confirm the tumor origin of the donor tissue. PMID- 1862111 TI - Monitoring of intracellular calcium in Saccharomyces cerevisiae with an apoaequorin cDNA expression system. AB - A method is described for measuring cytosolic free Ca2+ and its time-dependent changes in the yeast Saccharomyces cerevisiae by using the luminescent protein aequorin as a Ca(2+)-specific indicator. This method with intact yeast cells is labeled "in vivo" to distinguish it from methods with cell extracts, labeled "in vitro." A plasmid in which the apoaequorin cDNA was joined downstream from the glyceraldehyde-3-phosphate dehydrogenase gene promoter was constructed and introduced into yeast cells. The intracellular concentration of apoaequorin expressed by the cDNA was approximately 1 microM, which was high enough to detect the cytosolic Ca2+. Growth of the transformed cells was normal. In the in vitro method, apoaequorin in crude cell extracts was regenerated into aequorin by mixing with coelenterazine, the substrate for the luminescence reaction, whereas in the in vivo method, aequorin was regenerated by incubating intact cells with coelenterazine. Simultaneous addition of 10 mM CaCl2 and 10 microM A23187, a Ca2+ ionophore, to coelenterazine-incorporated cells generated luminescence. Coelenterazine-incorporated cells also responded to native extracellular stimuli. A mating pheromone, alpha-factor, added to cells of mating type a or alpha, generated extracellular Ca(2+)-dependent luminescence specifically in a mating type cells, with maximal intensity occurring 45-50 min after addition of alpha factor. Glucose added to glucose-starved G0/G1 cells stimulated an increase in extracellular Ca(2+)-dependent luminescence with maximal intensity occurring 2 min after addition. These results show the usefulness of the aequorin system in monitoring [Ca2+]i response to extracellular stimuli in yeast cells. PMID- 1862114 TI - [Factors in the evolution of home visits in psychiatry]. PMID- 1862116 TI - [The reception of the patient in the hospital]. PMID- 1862115 TI - [Infantile autism]. PMID- 1862117 TI - [An evaluation of the quantitative standards for nursing personnel reached in the 1st Special Surgical Pathology Department, Umberto I Polyclinic, Rome]. PMID- 1862118 TI - [Work organization and analysis. Inappropriate duties in nursing activities]. PMID- 1862120 TI - [An analysis of bill No. 5081 on the reform of the nursing health professions published in I.S.I.S. No. 13, March 25, 1991. Informazione Stampa Interesse Sanitario]. PMID- 1862119 TI - [The new Babel or about incommunicability]. PMID- 1862121 TI - [The integration of the mental health component into basic nursing education]. PMID- 1862122 TI - [The new text of bill No. 5081 on the reform of the nursing health professions]. PMID- 1862124 TI - Clinical and experimental approaches to dermal and epidermal repair--normal and chronic wounds. Proceedings of the Third International Symposium on Tissue Repair. Miami, Florida, January 10-14, 1990. PMID- 1862123 TI - Vascular factors govern healing in chronic wounds. PMID- 1862126 TI - Ketanserin promotes wound healing: clinical and preclinical results. PMID- 1862125 TI - Clinical trials with purified platelet releasate. AB - Clinical trials of PDWHF are ongoing and the final results are not yet available; however early lessons learned have allowed us to modify these trials. It is anticipated that the patient accrual will be completed within the next six months, and the last patient will complete the trial within the next year. At that time, we hope to have new insight into the role of PDWHF in the treatment of lower extremity ulcers. At this time, we are encouraged by the early improvement seen in patients entering the PDWHF versus saline trial. Preliminary results suggest that PDWHF improves the healing of diabetic ulcers of the lower extremity. PMID- 1862127 TI - The role of matrix components in human keratinocyte re-epithelialization. PMID- 1862128 TI - Spatial regulation of fibroblast proliferation: an explanation for cell regression at the end of the wound repair. PMID- 1862129 TI - Characteristics of fetal repair. PMID- 1862130 TI - Scarless wound healing in the fetus: the role of the extracellular matrix. PMID- 1862131 TI - Clinical spectrum of venous disease. PMID- 1862132 TI - Concomitant macrophage activation and fibroblast/lymphocyte inhibition by wound fluid: the "arginine-deficiency of inflammation" is a partial explanation. PMID- 1862133 TI - The temporal change in amino acid concentration within wound fluid--a putative rationale. PMID- 1862134 TI - Wound fluid: the growth environment. PMID- 1862135 TI - Effect of wound fluid on local and systemic immune responses. PMID- 1862137 TI - Wound dressings: current and future. PMID- 1862136 TI - Recruitment of mononuclear cells into wounded skin: mechanism and modulation. AB - In conclusion, we have shown that the development of specialized endothelium that supports lymphocyte and monocyte adherence may be a common biologic event associated with tissue injury or disease processes in the skin. We have shown that the adherence process is potentially regulated by cytokines that are secreted by infiltrating mononuclear cells. Studies are now in progress to identify the putative endothelial ligands, their interactions with the receptors and the factors that lead to the expression of the adhesion molecules. PMID- 1862138 TI - Methods to speed healing after skin biopsy or trichloroacetic acid chemical peel. PMID- 1862139 TI - The nonhealing diabetic ulcer--a major cause for limb loss. PMID- 1862140 TI - Assessment of wound healing speed in man. PMID- 1862141 TI - Animal models of wound contraction. PMID- 1862142 TI - Wound healing models to study connective tissue metabolism. PMID- 1862143 TI - Platelet-derived growth factor and impaired wound healing. PMID- 1862144 TI - TGF-beta and PDGF mediated tissue repair: identifying mechanisms of action using impaired and normal models of wound healing. PMID- 1862145 TI - Epidermal cell derived factor (EDF): partial purification and characterization. PMID- 1862146 TI - Role of growth factors in fracture healing. PMID- 1862147 TI - Retroviral-mediated gene transfer into transplantable human epidermal cells. PMID- 1862149 TI - Basic fibroblast growth factor accelerates tissue repair in models of impaired wound healing. PMID- 1862148 TI - The effects of epidermal growth factor and basic fibroblast growth factor on epithelialization of meshed skin graft interstices. PMID- 1862150 TI - Rethinking ischemic ulcers: from etiology to treatment outcome. PMID- 1862151 TI - The effect of nonspecific immune stimulation on wound healing. PMID- 1862152 TI - IL-1 as a potent inducer of wound re-epithelization. PMID- 1862153 TI - If wounds could talk. PMID- 1862154 TI - Design and implementation of clinical studies in chronic nonhealing wounds. PMID- 1862155 TI - Cultured epidermal allografts as biological wound dressings. AB - Recent advances in cell culture technology permit the generation of large stratified epithelial sheets appropriate for wound coverage. Autografts (sheets prepared from the patient's own skin) have proven life-saving in the treatment of large third-degree burns and have been successfully employed in the management of chronic ulcers. Allografts (sheets prepared from the skin of an unrelated donor) have also been used. In our experience, cultured allografts derived from neonatal foreskin provide a potent stimulus to healing in a variety of partial thickness wounds. Their application is a simple outpatient procedure which involves no discomfort for the patient. In contrast to autografting, no biopsy is necessary and use of cultured allogenic cells permits immediate grafts availability and possibility of stockpiling and preserving grafts for future use. Preparation of epithelial sheets suitable for grafting is also faster and easier with newborn than with adult donor cells. Newborn allografts have caused rapid healing of most previously refractory ulcers with long-term results comparable to those obtained with conventional split thickness grafting. We postulate that cultured allografts act by providing a temporary wound covering while releasing multiple cytokines that synergistically promote permanent reepitheliazation by previously quiescent host keratinocytes then stimulated to divide and migrate. Whether allografts are immunologically rejected in a clinically undetectable reaction or simply replaced stochastically by host keratinocytes is presently unknown. PMID- 1862156 TI - Clinical studies on growth factors in pressure sores: preliminary report. AB - Agents touted to benefit chronic non-healing wounds will become evermore prevalent. Examples, in addition to those cited, might include epictor (EGF) or platelet derived growth factor (PDGF). Although they may look promising in in vitro and experimental animal studies, they must be tested in humans. The pressure sore is a chronic three dimensional wound which lends itself to study of wound healing agents. It has been used for severe such trials and appears to be an excellent model for the continued study of peptide growth factors. PMID- 1862157 TI - Political change and course of affective psychoses: Berlin 1989-90. AB - In this study, the political change associated with the fall of the Berlin Wall in November 1989 was examined as a shared life event for the population of West Berlin. Its influence on the course of affective psychoses was studied in 67 patients in long-term treatment. Recurrences from November 1989 to March 1990 were compared with the same period 1 year before. While patients with bipolar affective psychosis did not show a difference in recurrences between the two periods, patients with unipolar depression had a significantly better and those with schizoaffective psychosis a significantly worse course of illness after November 1989 than in the year before. PMID- 1862158 TI - Diurnal variation of symptoms in seasonal affective disorder. AB - The classic melancholic pattern of depressive symptoms being worse in the morning was present in 3/4 of a sample of 47 seasonal affective disorder patients (SAD), as assessed by global ratings and self-ratings of diurnal variation (DV). The type of DV did not predict response to light, but it did predict relapse within a week: Only those SAD patients with symptoms worse in the evening or no DV did so. PMID- 1862159 TI - Migraine, psychiatric disorders, and suicide attempts: an epidemiologic study of young adults. AB - To determine the prevalence of migraine and the risks for psychiatric disorders and suicide attempts associated with it, we studied a random sample of 1,007 young adults from a large Health Maintenance Organization in the Detroit, MI area. The lifetime prevalence of migraine was 7% in males and 16.3% in females. The rate of migraine was higher in persons with lower education and was equal in whites and blacks. Persons with migraine were at increased risk for affective and anxiety disorders, nicotine dependence, and alcohol or illicit drug abuse or dependence. There was a consistent trend toward higher psychiatric comorbidity in migraine with aura than in migraine without aura. Coexisting anxiety, which generally preceded migraine, was associated with a marked increase in the odds of major depression. Persons with migraine had higher rates of suicide attempts than persons without migraine. The odds ratio for suicide attempts, adjusted for coexisting major depression and other psychiatric and substance use disorders, in migraine with aura was 3.0 (95% confidence interval, 1.4-6.6). The coexistence of migraine with major depression, anxiety disorders, and suicide attempts has important clinical and research implications. PMID- 1862160 TI - Heart rate variability in patients with major depression. AB - We have previously reported decreased heart rate variability upon standing in panic disorder patients compared with controls. In this study, we extend our report to include patients with major depression (n = 19). Compared to normal controls (n = 20) and panic disorder patients (n = 30), there was no significant difference in the immediate changes in heart rate upon standing in the depressed group. The standing heart rate variability (R-R variability) was significantly lower in panic disorder patients compared to both normal controls and depressed patients as indicated by the corrected standard deviations, the corrected mean consecutive difference, the corrected standard deviation of the mean consecutive difference of the R-R intervals, and the high frequency variability in successive R-R intervals, suggesting an increased vagal withdrawal in panic disorder patients, especially upon standing. There was no significant difference in any of the heart rate variability measures between depressed patients and normal controls. PMID- 1862161 TI - Continuous performance tests in schizophrenic patients: stimulus and medication effects on performance. AB - Medicated (n = 17) and unmedicated (n = 17) schizophrenic patients were compared to a normal control group (n = 19) on their performance on auditory and visual versions of the Continuous Performance Test (CPT). Within each stimulus modality, performance was examined on lexical and nonlexical target stimuli. Neuromotor competence was assessed on the basis of motor speed and proficiency. Normal subjects made fewer errors of all types than schizophrenic patients. Unmedicated patients made significantly more errors on nonlexical stimuli than medicated patients, with medication status found not to be associated with stimulus modality effects. Motor proficiency was associated with CPT performance in the medicated patients, but not the unmedicated ones, although this difference in correlations did not account for the group differences between these patients. The authors discuss the implications of these data for the type of cognitive and attentional functions that are affected by medication in schizophrenia. PMID- 1862162 TI - Thyrotropin and prolactin responses to ECT in schizophrenia and depression. AB - Thyroid stimulating hormone (TSH) and prolactin (PRL) plasma levels were studied during electroconvulsive therapy (ECT) in five schizophrenic patients in a simulated ECT (SECT) controlled experimental design. The data were compared to those obtained from a group of 10 depressed patients treated with ECT. In the schizophrenic group, both PRL and TSH increased significantly during ECT compared to SECT, as they did in the depressive group during ECT. Thus, the hormonal TSH and PRL profile during ECT is similar in schizophrenia and depression. It is concluded that the changes in TSH and PRL induced by ECT are specifically linked to the current or the seizure, and are not related to the type of psychopathology. PMID- 1862163 TI - Self-reports of childhood abuse in chronically psychotic patients. AB - A heterogeneous sample of 61 chronically psychotic patients were subgrouped according to the presence or absence of a self-reported history of childhood abuse. Patients reporting childhood abuse (n = 27) had an earlier age of onset, scored higher on the Dissociative Experiences Scale, reported more amnesia, and relapsed more frequently than patients not reporting abuse histories. Histories of childhood abuse and of past stimulant abuse predicted the score on the Dissociative Experiences Scale. A history of childhood abuse may thus contribute to the symptomatology and course of illness in some chronically psychotic patients. PMID- 1862164 TI - Confirming schizotypic personality configurations in hypothetically psychosis prone university students. AB - The personality features of hypothetically psychosis-prone (or schizotypic) subjects were examined. Schizotypic (n = 32) and control (n = 44) subjects were identified within a pool of 726 randomly ascertained nonclinical university students who had completed the Perceptual Aberration Scale (PAS) during a large scale screening study. Approximately 4-6 months after the initial screening, the schizotypic and control subjects completed the Minnesota Multiphasic Personality Inventory (MMPI). Schizotypic subjects as a group displayed an average MMPI profile consistent with schizotypic personality features, whereas the control subjects did not. Moreover, multivariate profile analysis revealed that the schizotypic group MMPI profile differed significantly in shape from the control group profile. Finally, schizophrenia-related MMPI high-point codes were five times as prevalent among the PAS-identified schizotypic subjects as among the controls. The results suggest that the PAS identifies individuals who show schizotypic personality MMPI configurations and may carry a latent vulnerability for schizophrenia or, more broadly, psychosis. PMID- 1862166 TI - Response bias associated with asking former study participants to assist in new research. AB - To limit research costs, former parent-participants from a completed pediatric neurology study were asked to assist with new research on behavioral contributors to childhood injury. An evaluation of the response bias associated with this recontact effort showed that 224 parents who completed the survey did not differ from the 51 who failed to complete it in race, age, education, or income. Nonresponders were significantly less likely to be married than responders. PMID- 1862167 TI - Geophysical variables and behavior: LXV. Seasonal changes in mood in opioid addicts on the Addiction Research Center Inventory. AB - Seasonal changes in mood using the Addiction Research Center Inventory (ARCI) were tested in 243 male opioid addicts when they were free of drug and withdrawal effects. No significant changes were found on scales which measure euphoria (MBG), tension-anxiety (LSD), excitement (Ex), or dysphoric effects (SOW). A significant difference between seasons was found for lowered motivation (PCAG) in the summer and spring relative to winter, but these effects were not consistent with a winter seasonal affective disorder. Significant changes were more common for spring-fall and summer seasons relative to winter on items of the inventory. PMID- 1862165 TI - Heterogeneity of schizophrenia: relationship to latency of neuroleptic response. AB - Patients with an index diagnosis of schizophrenia were compared to patients with an index diagnosis of schizophreniform disorder to determine if they differed in latency to therapeutic response to haloperidol. The results of a survival analysis showed that patients with a diagnosis of schizophreniform disorder responded to haloperidol significantly more rapidly than did patients with a diagnosis of schizophrenia. Inspection of time-to-response slopes revealed that approximately 75% of the schizophreniform patients responded to neuroleptics on or before day 8 of treatment, whereas only 20% of the schizophrenic patients responded this rapidly. Forty percent of schizophrenic patients responded between day 8 and day 18, and 30% between day 18 and day 36. These results indicate that schizophreniform disorder has been successfully separated from schizophrenia in DSM-III, at least in relationship to drug response. PMID- 1862168 TI - Drug use and its relation to high school students' activities. AB - In a high school in a suburb of Detroit, students' attitudes toward, use of, and money spent on drugs, as well as possible alternative activities, were investigated. The sample included 42 enrolled in alternative education designed for students at risk for drug abuse, pregnancy, etc., who might attend college if guided carefully, and 65 regular students who were a mix of college and noncollege bound. The two groups did not differ in actual drug use, most likely because those who recommended students to the alternative education program used low grade point average and not drug use as criterion. Very few "hard" drugs were used. Most frequently used were readily available drugs such as alcohol. Use of a drug, spending money on it, or believing that it is all right for adolescents to use the drug did not automatically indicate frequent use of the drug. Contrary to adults' expectations, "hangin' out" with peers decreased use of "soft" drugs. Family activities for some involved the use of hard drugs together or the condoning of use. To create effective drug-prevention programs, the effects of different activities need to be explored further, and admission criteria need to be well delineated. PMID- 1862169 TI - Therapists' causal attributions of clients' problems and selection of intervention strategies. AB - Therapists' choices of intervention strategies are influenced by many factors, including judgments about the bases of clients' problems. To assess the relationships between such causal attributions and the selection of intervention strategies, 196 counselors, psychologists, and social workers responded to the written transcript of a client's interview by answering two questionnaires, a 1982 scale (Causal Dimension Scale by Russell) which measured causal attribution of the client's problem, and another which measured preference for emotional, rational, and active intervention strategies in dealing with the client, based on the 1979 E-R-A taxonomy of Frey and Raming. A significant relationship was found between the two sets of variables, with internal attributions linked to rational intervention strategies and stable attributions linked to active strategies. The results support Halleck's 1978 hypothesis that theories of psychotherapy tie interventions to etiological considerations. PMID- 1862170 TI - How business professionals view their stress. AB - Differences in stress for business professionals by sex, age, marital status, stress levels, job classification, having children and pets were investigated. Subjects were 80 business professionals who responded to the Tennessee Stress Scale-L inventory which provides three subscales (Stress Producers, Coping Mechanisms, and Stress Symptoms) and Total Stress. Significant differences were found between 40 men and 40 women and among stress level groups on Stress Producers, Stress Symptoms, and Total Stress scores. PMID- 1862171 TI - Attitude, anxiety, and social readjustment toward learning disabilities by student teachers. AB - 84 student teachers from undergraduate classes at a western university in Kansas completed a 9-question checklist of learning disabilities before interacting with a behavioral disordered/learning disabilities teacher, a paraprofessional, and a high school learning-disabled student. After the dialog, the student teachers completed a Social Readjustment Rating Scale, Breskin Rigidity Test, the Self evaluation Questionnaire: State and Trait Anxiety, and the same 9-question checklist with one additional question ("Now that you have seen a learning disabled student has it affected your opinion of learning disabilities?"). The dialog affected 63% of the students' opinions while 31% stated the presentation did not affect their opinion (6% were missing or not completed). Persons who experienced more life-changes and problems tended to rate or view learning disabilities more negatively. The more trait anxiety experienced by the students, the lower they rated learning disabilities after the presentation. PMID- 1862172 TI - Attitudes related to work of adolescents in the United Kingdom and Japan. AB - This study was designed to provide data for notions that differences in achievement motivation in different nations may contribute to differences in national rates of economic growth. The nations investigated were the United Kingdom and Japan as representatives of low and high rates of economic growth in the decades after the end of World War II. Data were collected from college students for motivations and attitudes related to work. British students had higher achievement motivation, while Japanese students had higher competitiveness motivation and strong money beliefs. Differences in career preference between the nations were also presented. The relationship between motivations and attitudes to work with career preference were examined for each nation. PMID- 1862173 TI - Sustaining fantasies and the 16 PF. AB - This study examined the relationships between the Sustaining Fantasy Questionnaire (SFQ) and the 16 PF for 63 college students. The questionnaire is a self-report measure of characteristic fantasies used to reduce negative affect and maintain self-esteem. High scores on the fantasy scales having to do with power and revenge, death and illness, withdrawal and protection, and restitution, and on the scales measuring negative affect and the inability to produce comforting images were all associated with 16 PF indications of psychological distress. PMID- 1862174 TI - School stress reported by children in grades 4, 5, and 6. AB - Stress in the school environment of 269 elementary school children attending Grades 4, 5, and 6 of a metropolitan school district were assessed using the School Stress Questionnaire. The effects of sex, ethnic background (minority vs nonminority), type of classroom placement (regular education versus special education), and family structure (traditional versus nontraditional or divorced) were investigated. Children from nontraditional or divorced families had significantly higher school stress than children from intact families. The possibility that these results are a reflection of society's negative attitudes toward children living in nontraditional families is raised. PMID- 1862176 TI - Use of the Hereford Parent Attitude Survey as an outcome measure in parent education research. AB - Research on outcome evaluation published since 1980 on the Hereford Parent Attitude Survey was reviewed in terms of sample size, type of parent training program used, and the scales' sensitivity to change in parental attitudes after intervention. Some support for the sensitivity of the Hereford was found, and, as an evaluation device to assess whether program goals have been achieved, the scale proved to be a useful instrument. The Hereford scale can be applied with reasonable confidence in research on parenting and in strategies to enhance effective parenting. PMID- 1862175 TI - Late onset of alcoholism among older midwestern men in treatment. AB - 60 men were administered a questionnaire to assess whether the prevalence of alcoholism in men over 60 years of age in alcoholism treatment centers parallels the reported rates of late-onset for one-third or more alcoholics. Analysis showed 11% of the subjects were of late onset while 33% were quasilate onset. There were no significant differences in the life stress between alcoholics of early and later onset. PMID- 1862177 TI - Compulsive procrastination: some self-reported characteristics. AB - In Sample 1, 46 procrastinators compared with 52 nonprocrastinators claimed lower self-esteem, greater public self-consciousness and social anxiety, and a stronger tendency toward self-handicapping. In Sample 2, 48 procrastinators compared with 54 nonprocrastinators reported a weaker tendency toward seeking self-identity information but a stronger tendency toward a diffuse-identity style, yet there were no significant differences in verbal and abstract thinking abilities. Further research must provide evidence for persistent procrastination as a personality disorder that includes anxiety, avoidance, and a fear of evaluation of ability. PMID- 1862178 TI - AIDS--intervention works; "education" is questionable. AB - A decrease in or leveling off of new cases of transfusion-related AIDS coupled with continued increases in homosexual and IV drug cases suggests that intervention by barring contaminated blood has worked and "education" has worked less well, if at all. Current evidence suggests that the blood-bar resulted in the change in new AIDS cases among children within 3 years and among adults within 3 1/2 years. PMID- 1862179 TI - Intelligence and race: further comments on J. P. Rushton's work. AB - A review of some implications of J.P. Rushton's 1988 and 1990 work on racial differences in brain mass (size or weight) suggests that his comments do not constitute a viable scientific theory. PMID- 1862180 TI - Stable vs unstable weight history, body-image, and weight concern in women of average body weight. AB - The focus of this study was the effect of unstable weight history on current body image among women. Participants were 45 college women of average weight (median age = 23 yr.); 15 had stable weight histories, 15 had past lowest weights 15% or more below current weight, and 15 had past highest weights 15% or more above current weight. The women were assessed on perceptual and attitudinal measures of body-image and a self-report measure of preoccupation with weight. In comparison to women with stable weight histories, those with unstable weight histories indicated greater dissatisfaction with the shape and size of their bodies, expressed more negative body attitudes, and reported increased concern about weight. Women with high weight histories overestimated their frontal body-size and expressed greater dissatisfaction with frontal size than women with low weight histories, but the two groups did not differ significantly on any of the other dependent measures. Possible explanations for increased body-image disturbance and weight concern among women with unstable weight histories are presented. PMID- 1862181 TI - Race, brain size, and intelligence: another reply to Cernovsky. AB - Five sets of observations require explanation. Firstly, within both black and white populations there is a small positive correlation between IQ and brain size whether or not there is control for body size. Secondly, racial differences in average brain size occur such that Mongoloids greater than Caucasoids greater than Negroids especially with control for body size. Thirdly, mammals with larger brains relative to their bodies perform better on learning tasks than mammals with smaller brains relative to their bodies. Fourthly, average racial differences on measures of cognitive performance parallel the differences in average brain size. Fifthly, average racial differences on numerous other traits parallel the differences in intelligence and brain size. It is incumbent on scientists to explain these facts. PMID- 1862183 TI - Crisis intervention: long-term training effects. AB - 10 months following a crisis-intervention training program which focused on interpretation of signal events, 17 participants more frequently reported increased belief in their ability to recognize the need for intervention and to intervene effectively than did 22 control subjects. Perceived frequency of intervention by trained participants, however, had decreased rather than increased. Implications of the findings and recommendations for research are discussed. PMID- 1862182 TI - Self-concepts of mothers who show mental retardation. AB - The Tennessee Self-concept Scale was orally administered to 27 mothers with mental retardation and self-administered to 95 mothers whose children attended daycare in the areas in which the former mothers lived. Analyses showed that the mothers with mental retardation scored significantly lower on all subscales. Where 72% of the comparison group scored above a recommended cut-off indicative of a positive self-concept, only 33% of the mothers with mental retardation did. Comparisons of the 27 mothers with mental retardation (18 with positive versus 9 with negative self-concepts) on personal, child, family, and other background variables suggested different relationships for the two groups. Cross-validation of the present work and studies of the actual childcare of these latter two groups of mothers are needed. PMID- 1862184 TI - Negative schemas and depression in normal college student volunteers. AB - The present research explored the intrinsic relationship of self-reported depressive symptoms and cognitive distortions as proposed by Beck and others. A devised scale of cognitive distortions was correlated with scores on the Beck Depression Inventory for 67 college volunteers. A significant value of 0.59 was found, supporting our hypothesis. There were no sex differences on either scale. PMID- 1862185 TI - External locus of control in children of alcoholics. AB - The relationship of type of home of origin [alcoholic parent(s) versus nonalcoholic parent(s)] to locus of control was assessed. Perceived level of parental alcohol abuse (MAST score) did not predict 121 students' locus of control. However, external orientation was significantly and positively correlated with having a parent who drank heavily and scores on the Beck Depression Inventory and significantly and negatively correlated with the Rosenberg Self-esteem Inventory and the Possible Self Questionnaire. PMID- 1862186 TI - Health locus of control, self-concept, and anxiety in pediatric cancer patients. AB - In a study of 38 pediatric cancer patients, standardized measures of health locus of control achieved only modest to unsatisfactory reliability. Correlations between health locus of control and measures of self-concept and anxiety were low. Some of the items from the scales, however, were significantly related to the patients' feelings of well-being, positive self-concept, and reduced levels of anxiety. An examination of these item correlations and information from a qualitative interview suggest that hopefulness may be more salient for pediatric cancer patients than locus of control. Further research on children's health locus of control should distinguish between clinical and healthy populations. PMID- 1862187 TI - On the nature of attachment in a borderline population: a preliminary investigation. AB - Analyses of interpersonal behavior within a borderline population usually focus on object relations variables. In contrast, this preliminary research focuses on the nature of attachment styles and its relation to behavioral pathology. 24 hospitalized borderline patients were administered an Attachment Style Inventory and Millon Clinical Multiaxial Inventory. Analysis confirms predicted differences in attachment style between the borderline and normal control samples as well as indicates that a dependent style of attachment within this borderline sample is associated with less pathology than an avoidant, hostile, or resistant/ambivalent style. The implications of this preliminary work for full-scale research are addressed. PMID- 1862188 TI - Alcohol-related expectancies for self and others reported by alcoholic men and women. AB - A questionnaire used by Rohsenow in 1983 was administered to 87 alcoholic men and women taking part in rehabilitation programs at local Swedish outpatient rehabilitation clinics. The purpose was to explore their alcohol-related expectancies for themselves and for others and to compare these with the results from other similar studies in other cultures. The answers, scored according to Rohsenow's eight factors, indicated that alcoholics expected larger positive and negative effects for others than for themselves. This discrepancy was slightly modified by such variables as sex, age, and drinking habits. Alcoholics in Sweden seem to have alcohol-related expectancies similar to those of social drinkers both in Sweden and in other Western countries. PMID- 1862189 TI - Treatment outcomes of Vietnam veterans with Posttraumatic Stress Disorder. AB - This study examined changes on the Millon Clinical Multiaxial Inventory for 45 Vietnam veterans who completed a specialized inpatient treatment program. The average length of stay for these veterans was 140 days. Patients' scores on the Millon decreased on 12 of the 20 scales and increased on 8, and their Posttraumatic Stress Disorder-related symptoms of anxiety and dysthymia decreased significantly. Posttraumatic Stress Disorder-related character styles, schizoid, avoidant, and passive-aggressive, also showed significant decreases. PMID- 1862190 TI - Health psychology and clinical psychology: a comparison through content analysis. AB - Extension of a previous analysis of articles published in two journals representative of health psychology and two in health education showed some similarities and differences. The present analysis of 100 papers from two journals in health psychology and 495 from two in clinical psychology clearly shows health as a subspecialty of clinical psychology. PMID- 1862191 TI - Comparison of three antismoking interventions among pregnant women in an urban setting: a randomized trial. AB - This study examined smoking cessation and cigarette reduction of indigent inner city pregnant women (n = 193) who completed one of three interventions: a special video program based on their perceptions of the effects of smoking during pregnancy, the American Lung Association's "Freedom From Smoking For You and Your Baby" program, or the usual physician's advice. Six percent of the women quit smoking, and 43% reduced the number of cigarettes they smoked. There were no significant differences among the three groups for either the number who quit smoking or who reduced the number of cigarettes smoked. PMID- 1862192 TI - Dimensions of sexual behaviour in homosexual men: replicability across time and country. AB - Data on sexual practices in the past two months were obtained from 176 Australian and 159 New Zealand homosexually active men. Factor analysis yielded three major underlying dimensions of homosexual behaviour in each sample, accounting for 53.4 and 54.0% of total variance at baseline and 55.1 and 62.1% at follow-up, respectively. These three dimensions represented unsafe sex involving predominantly anal activity, safe (oral and mutual masturbatory) sex without condoms, and safe anal sex with condoms and withdrawal. Comparison of the four matrices (two countries by two times), using Cattell's S index, indicated high stability of the factor structure across countries and times. These three dimensions of homosexual behaviour appear to represent consistent behavioural clusters across samples and times. They suggest that use of these dimensions in further research on homosexually active men is warranted and that homosexual activities cluster into a number of limited dimensions on which sexual behaviours are interrelated. PMID- 1862193 TI - Headache and sensation seeking. AB - According to the cognitive theory of sensation seeking, headache sufferers were predicted to score lower than controls on Zuckerman's Sensation Seeking Scale. 26 subjects who experienced chronic headaches scored significantly lower than a group of 26 controls. The relationships between the Sensation Seeking Scale and a number of personality tests are described. Replication of the findings on this scale with headache patients is encouraged as well as exploration of other personality dimensions which show significant relations with sensation seeking. PMID- 1862194 TI - Correlates of sexual interest among elderly men. AB - Interview data were collected from 46 English elderly men (age 70 to 94 years) relating to attitudes, psychological traits, and life satisfaction. Sexual interest was not related to life satisfaction or marital status but was significantly correlated with measures of emotional expressivity, personal identity, as well as regrets about the past. Findings are discussed in terms of Erikson's later stages of ego development. PMID- 1862195 TI - Assessment of coping strategies, social support, and general health status in individuals with diabetes mellitus. AB - This study examined 51 individuals (30 men, 21 women) who participated in an outpatient diabetes education program. Participants with higher perceived support by friends and problem-solving coping strategies were healthier, while those exhibiting a wish-fulfillment coping style were less healthy. Perceived family social support was much greater for Type II (noninsulin-dependent) individuals than for Type I (insulin-dependent) individuals. Men perceived greater family support, were more likely to use problem-solving coping, and were healthier than women; however, both wish fulfillment and detachment coping were more prevalent in women. Perceived support from family and friends increased with education. Implications for diabetes education programs are also introduced. PMID- 1862196 TI - Suicidal behavior and Becker's definition of irrationality. PMID- 1862198 TI - Qualitative and quantitative sex differences in self-reported aggressive behavioral characteristics. AB - Aggressive behavioral characteristics were assessed in a large group of men and women by a self-report instrument, the Aggression Inventory. Significant gender differences appeared on four factors in which men reported more physical aggression and verbal aggression than did women. Further, men had higher scores on measures of impulsiveness and lack of patience than women, while women reported being more likely to avoid confrontation. In addition to these quantitative sex differences in self-reported behavior, factor analyses indicated qualitative differences by sex, wherein most of the variance for women centered on verbal aggression, while physical aggression was the first factor for men. PMID- 1862197 TI - Effect of hazard warning on workers' attitudes and risk taking behavior. AB - Until recently, the issue of job hazards has been largely ignored as a research and theoretical topic in business and management disciplines although workers' perceptions and assessments of job hazards are of significance to managers. In this paper are reported results of an experiment conducted in Egyptian chemical firms to test the generality of an implicit rational model used to explain employees' reactions to and perceptions of job hazards. Four hypotheses were tested: (1) workers' subjective estimates of their job hazards are positively related to the objective hazard, (2) workers' subjective estimates of a prospective new job hazard will vary directly with the extent of hazard communicated by the new product label, (3) workers' demand for new hazard wage premiums will vary directly with perceived prospective new work hazards, (4) workers' intention to quit the job will vary directly with subjective and objective estimates of job hazards. All hypotheses were supported. The rational worker model appears to be a general explanation for workers' responses to hazardous jobs and information on hazards. This model not only holds for USA workers but also for those in a nonwestern culture. Implications for management and the industrial setting are discussed. PMID- 1862199 TI - Criterion-related validity of a new classification scheme for institutionalized mentally retarded individuals. AB - Two studies were carried out to test the validity of a new three-cluster classification scheme. The association of cluster membership with both clients' movement and program placement was significant, but only in the case of the latter criterion was prediction improved by knowledge of a client's cluster membership. PMID- 1862200 TI - 30th annual meeting of the New Clinical Drug Evaluation Unit (NCDEU). May 29 to June 1, 1990, Key Biscayne, Florida. Abridged proceedings. PMID- 1862201 TI - Clinical significance of reversed vegetative subtypes of recurrent major depression. AB - The significance of reversed vegetative forms of atypical depression (AD) was investigated in a sample of 211 outpatients with recurrent major depression. Consistent with several earlier reports, AD patients were younger, had fewer typical symptoms of melancholia, and responded slower to imipramine and psychotherapy treatment given according to protocol. There were few differences between reversed vegetative AD patients with reactive and nonreactive moods; both subforms of AD responded well to monoamine oxidase inhibitor when crossed over after initial protocol treatment failed. PMID- 1862202 TI - The depressed borderline: one disorder or two? AB - Depression in the borderline patient may present as a reactive mood state, an expression of character, or an independent comorbid affective disorder. The symptom picture is most often heterogeneous, "atypical," and chronic. Pharmacologic trials with tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) produce modest improvement on a variety of symptoms, though not always on depression. Medication effects on depressed mood in borderline personality disorder (BPD) are independent of comorbid diagnoses of major depression, atypical depression, or hysteroid dysphoria. Residual symptoms are the rule. A literature review, including studies of comorbidity, longitudinal followup, family history, and laboratory and pharmacotherapy studies, suggests that the borderline patient has both a core biologic affective dysregulation and a pathologic personality organization. The combination of constitutional and psychodynamic etiologies for borderline pathology requires consideration of both pharmacotherapy and psychotherapy in any comprehensive treatment. PMID- 1862203 TI - Is there an alternative to the randomized controlled trial? AB - The advantages of the concurrently randomized controlled trial as a device to assess the efficacy of drugs intended for use in the field of psychiatry are reviewed. The importance of "assay sensitivity" is discussed and illustrations of errors that can arise when inferences about efficacy are based upon comparisons that find no difference between experimental and standard treatments are presented. These illustrations are derived from data collected in two different pre-marketing commercial drug development programs. Also discussed is the argument that controlled trials are inappropriate devices to test drug efficacy because of their alleged lack of sensitivity to drug effects. PMID- 1862204 TI - Continuation and maintenance treatment of major depression with the monoamine oxidase inhibitor phenelzine: a double-blind placebo-controlled discontinuation study. AB - Long-term treatment with antidepressant drugs has received little attention until recently. A study is reported comparing the effectiveness of maintenance treatment with phenelzine in responding major depression patients. If they responded initially to nonblind phenelzine treatment and sustained remission for 16 weeks, patients were randomized to 2-year double-blind treatment with phenelzine 60 mg/day, phenelzine 45 mg/day, or placebo. Both doses of phenelzine were significantly better than placebo in preventing relapse of depression. Phenelzine 45 mg/day may be an optimal maintenance dose for many patients. PMID- 1862205 TI - Treatment of age-associated memory impairment with guanfacine. AB - Alpha2 adrenergic agonists have been shown to improve memory test performance in amnesic humans and aged nonhuman primates. In a group of drugs in this class that were tested for their effects on age-related memory impairments in aged monkeys, guanfacine was the most effective for improving mnemonic function at doses that were without significant side effects. These data prompted studies of guanfacine for its effect on learning and memory in persons with age-associated memory impairment (AAMI), the results of which are now reported. The data suggest that guanfacine may have modest mood-improving effects but had no significant effects on learning and memory in the subjects tested. PMID- 1862206 TI - Reliability, validity, and a total score cutoff for the dyskinesia identification system: condensed user scale (DISCUS) with mentally ill and mentally retarded populations. AB - The reliability and validity of the Dyskinesia Identification System: Condensed User Scale (DISCUS) are presented for mentally ill (n = 2,822) and mentally retarded (n = 4,649) populations, as are DISCUS item means and standard deviations. A total score cutoff was developed and tested against physician diagnosis and the Research Diagnoses for Tardive Dyskinesia (RD-TD) intensity criterion. DISCUS total score significantly increased as age increased and was significantly greater for 108 TD cases compared to 108 matched no-TD cases. The DISCUS total score of 5 or above was significantly associated with physician TD diagnosis, the RD-TD intensity criterion, and an increasing number of individuals meeting the cutoff score as age increased. Based upon the data, the DISCUS is a reliable and valid TD assessment instrument. It is concluded that the DISCUS cutoff score is as valid a measure of TD as the current operationally defined RD TD intensity criterion. PMID- 1862207 TI - Response to desipramine treatment in adolescent major depression. AB - Thirty adolescents (ages 15-20) who met DSM-III-R criteria for major depressive disorder completed a double-blind, placebo-controlled, 6-week, fixed-dose (200 mg daily) study of desipramine (DMI). Thirty-three percent of the placebo group and 50 percent of the DMI group improved (greater than or equal to 50% change on the Hamilton Rating Scale for Depression). Subjective reports of adverse effects did not significantly differentiate the two groups. Major adverse effects, necessitating study discontinuation, occurred solely in the DMI group. PMID- 1862208 TI - Random regression models for multicenter clinical trials data. AB - A random-effects regression model is proposed for the analysis of data arising from multicenter clinical trials. Advantages of the random regression model (RRM) in this context include that it allows for varying numbers of subjects within the different centers, it can assess the influence of variables measured both at the level of the subject and at the level of the center on the subject's clinical outcome, and it controls for and estimates the amount of intracenter variation that is present in the data. An example utilizing data collected in the National Institute of Mental Health schizophrenia collaborative study, where subjects were clustered within nine centers, illustrates the usefulness of the statistical model. Other applications and extensions of RRM within a psychiatric framework are discussed. PMID- 1862209 TI - Early prediction of relapse in schizophrenia: an application of receiver operating characteristic (ROC) methods. AB - We compared different methods of identifying prodromal periods with regard to their ability to predict relapse in schizophrenia. Fifty stabilized schizophrenic patients, who received a low dose of schizophrenic patients, who received a low dose of fluphenazine decanoate (5 to 10 mg every 2 weeks) were monitored with weekly evaluations to determine whether they met criteria for nonpsychotic prodromal episodes. We evaluated three different scales: (1) the Anxious Depression subscale of the Brief Psychiatric Rating Scale (BPRS); (2) a modification of the patient self-report Early Signs Questionnaire and (3) the Idiosyncratic Prodromal Scale (IPS). We used receiver operating characteristic (ROC) methods for comparing the different instruments as methods for predicting whether patients would or would not demonstrate a psychotic exacerbation in the 4 weeks following the assessment. Both the IPS and the BPRS cluster scores were better than chance at correctly identifying periods of vulnerability to psychotic exacerbation. The ROC analyses suggest that relatively small changes in the signs and symptoms of chronic schizophrenic patients in maintenance treatment may be clinically meaningful. PMID- 1862210 TI - Steady-state plasma level prediction for haloperidol from a single test dose. AB - Due to large interindividual variabilities in kinetics of haloperidol (HPDL), empirically adjusting the dose to achieve steady-state plasma levels (Css) is a time consuming process. We report a method to individualize doses to achieve the desired Css from the observed plasma level 24 hours after a single test dose. Twenty-eight acutely psychotic patients, after up to 2 weeks of inhospital drug washout, received a 15-mg oral "test" dose of HPDL and 24- and 48-hour plasma levels were measured. They were then randomly assigned to empirically determined doses of HPDL (2, 4, or 10 mg b.i.d.) to achieve a low, medium, or high Css. The 24-hour plasma level after the test dose, the final Css, and the dose required to achieve that Css were analyzed by a linear regression model. The log Css in terms of the log dose revealed a strong linear relationship (R2 = .78, n = 28), which was further improved by the addition of the 24-hour log plasma level (R2 = .87). PMID- 1862212 TI - Supreme Court affirms 8 bargaining units per hospital. PMID- 1862211 TI - Electroconvulsive therapy in the United States. AB - In 1990, electroconvulsive therapy (ECT) celebrated 50 years of continuous use in the United States. After many trials and tribulations, this treatment modality has experienced a resurgence of interest in recent years. Contemporary research has helped to both maximize benefits and minimize risks, as ECT has grown technologically into a sophisticated procedure administered by highly trained practitioners. Given the substantial growth in knowledge about ECT, the American Psychiatric Association has recently developed comprehensive clinical guidelines for its practice. The present paper provides an overview of the history of ECT in the United States, the manner in which it is used at present, and areas of active research interest. PMID- 1862214 TI - Legal case briefs for nurses. LA.: nurse inserts catheter over pt.'s objection: battery; IL.: nurse leaves station--termination: at will employment. PMID- 1862213 TI - Failure to monitor patient: deplorable nursing care. Case in point: Harrington v. Rush-Presbyterian-St. Luke's (569 N.E. 2d 15--IL (1990)). PMID- 1862215 TI - Electric shock for infant: disciplinary action for nurse. Case in point: Cafiero v. N.C. Board of Nursing (403 S.E. 2d 582--NC (1991)). PMID- 1862216 TI - Lithium administered by eye drops: a better treatment for bipolar affective disorder? AB - 1. Bipolar affective patients are supersensitive to light. 2. Lithium treatment decreases retinal sensitivity to light. 3. Recent findings concerning lithium perturbation of the function of various members of the G proteins family including transducin (G1), as well as findings of lithium sensitive hyperactive G proteins in mononuclear leukocytes of patients with mania led to the hypothesis that lithium sensitive hyperfunctional G1 is responsible for the supersensitivity to light in affective patients. 4. Thus, a change in the usual route of lithium administration into eye drops delivery is hypothesized to be more efficient clinically, with the advantages of shortening the time delay necessary to achieve therapeutic effects, and having less systemic side effects and reduced toxicity. PMID- 1862218 TI - Pituitary abnormalities in eating disorders: further evidence from MRI studies. AB - 1. The frequent occurrence of hypothalamo-pituitary dysfunction in patients with eating disorders as well as prior reports that nutritional and endocrine status influence pituitary morphology, led us to hypothesize that pituitary size and shape may be altered in patients with eating disorders. 2. Magnetic resonance imaging (MRI) does not use ionizing radiation and is currently one of the most feasible modalities available to study the pituitary gland in vivo. Using MRI, we have previously reported in a preliminary study that female patients with eating disorders had significantly smaller pituitary glands than controls. In addition MRI excluded any pituitary mass lesions. 3. In this report, we confirm our previous MRI findings and provide further evidence of pituitary abnormalities in an expanded sample of eating disorder patients. Preliminary data on pituitary volume estimates from MRI scans are provided for a subset of patients and controls. PMID- 1862217 TI - Glycosaminoglycan polysulfate in the treatment of old age dementias. AB - 1. In a multicenter, placebo-controlled, double-blind clinical trial in 155 elderly patients with cognitive decline, glycosaminoglycan polysulfate was found to be a therapeutically effective agent in the treatment of old age dementias. 2. Treatment with glycosaminoglycan polysulfate in the daily dosage of 600 LRU, administered on the basis of a divided dosage schedule for 12 weeks, was significantly superior to an inactive placebo on several outcome measures including the Wechsler Memory Scale-Russell Revision (Easy Paired Associates Learning and Immediate Visual Reproduction), Mini Mental State Examination, the Sandoz Clinical Assessment Geriatric (Cognitive Dysfunction and Depression), Hachinski Dementia Scale, Brief Psychiatric Rating Scale (Confusion and Depressive Withdrawal) and Global Improvement Scale of the Clinical Global Impression. 3. Adverse effects with glycosaminoglycan polysulfate were few and mild. The drug was equally well tolerated and equally effective in the two major dementias of old age, i.e., primary degenerative and multi-infarct. The number of abnormal laboratory test readings remained essentially unchanged from pre treatment to post-treatment. PMID- 1862219 TI - Selective anorexigenic effects of corticotropin releasing hormone in the rhesus monkey. AB - 1. Rhesus monkeys were equipped with a novel intracerebroventricular (i.c.v.) cannula system and trained to respond under operant schedules of food presentation or termination of stimuli associated with the delivery of shock (escape). 2. CRH decreased food-maintained behavior in a dose-related manner over the range of (0.3-10 micrograms/kg) but did not affect escape responding, demonstrating a selective effect on food-maintained responding. 3. This selective effect was related to the tendency for responding to stop after delivery of a food pellet when higher doses of CRH were given, consistent with the notion that a conditioned aversion to food was established in the presence of CRH. 4. This may suggest that in hyperaroused clinical states such as depression and anorexia nervosa, focus is shifted away from appetitive tasks as a result of increased levels of CRH. PMID- 1862220 TI - Ontogeny of phenylalanine (endogenous cholecystokinin) induced modulation of food intake in normal and undernourished rats. AB - 1. The development of endogenous cholecystokinin (CCK) effects on food intake was studied in normal and undernourished growing rats of postnatal day 1-22. 2. Food intake was estimated by recording the gain in body weight before weaning. 3. l phenylalanine, a potent stimulant of endogenous CCK release, suppressed 30 min food intake in normally nourished pups of day 7-15 or more but not of day 1-6 rats. 4. However, l-phenylalanine did not affect 24 hr gain in body weight day 1 6 or more, rat pups. 5. l-phenylalanine neither suppressed 30 min food intake nor affected 24 hr body weight in day 16-19 or 20-22 undernourished rat pups. 6. The study suggests that the endogenous CCK satiety effects appear early in the second week of postnatal life in normally nourished rats, whereas in undernourished rat pups it does not appear till day 20-22. PMID- 1862221 TI - Opiate-dopamine interactions in the neural substrates of acoustic startle gating in the rat. AB - 1. The acoustic startle reflex (ASR) was measured in adult male Dawley rats using startling acoustic stimuli presented either alone or 60-500 msec after a weak acoustic prepulse. 2. The inhibition of the ASR by the prepulse, termed "prepulse inhibition" (PPI), was blocked in animals treated either with the indirect dopamine (DA) agonist d-amphetamine (AMPH) or with the direct DA receptor agonist apomorphine (APO). 3. Pretreatment with the opiate receptor antagonist naloxone (NAL) prevented the AMPH-induced loss of PPI, but did not diminish the APO induced loss of PPI. 4. The opiate heroin had no significant effect on PPI. 5. Dopaminergic mechanisms that modulate PPI in the rat may be regulated by opiate systems that act presynaptic to the DA receptor; brain opiate receptors may not have direct effects on startle gating independent of this opiate-DA interaction. PMID- 1862222 TI - Lithium-TCA induced malignant syndrome. Case report. AB - 1. The authors describe some adverse reactions, induced by lithium and TCA administration, in a 71 years old woman treated for mixed bipolar disturbance. 2. The case history here described, is perfectly compatible with a diagnosis of Malignant Hyperthermia (MH). 3. Utility of the association of hypothalamic phospholipid liposomes (HPL) and myorelaxants in the reduction of these lithium side effects, is discussed. PMID- 1862223 TI - Oxytocin-induced prostaglandin release from perifused bovine caruncular and intercaruncular endometrial tissue on days 20, 30 and at first estrus postpartum. AB - Twenty-two multiparous Brahman x Hereford F1 cows were utilized to determine the effect of oxytocin (OT) on prostaglandin F2 alpha (PGF) release from caruncular and intercaruncular endometrial tissues and prostaglandin E2 (PGE) release from intercaruncular tissue. The previously gravid uterine horn was removed on d 20 postpartum (n = 7), on d 30 postpartum (n = 7) or the uterine horn ipsilateral to the dominant follicle was removed 12-18 h after onset of first behavioral estrus postpartum (ES; n = 8). Tissues (200 mg wet wt) were cultured in Nutrient Mixture F-10 medium in a perifusion system. The medium and tissues were aerated with 95% O2: 5% CO2 and temperatures were maintained at 39 degrees C. The flow rate was 100 microliters/min and fractions were collected at 20 min intervals for 400 min. After a 2 h settling phase, the tissues were challenged with 1, 2 or 4 micrograms [Asu1,6]-OT/ml of media for 1 h. Basal release of PGE and PGF on d 20 was greater than on d 30 and at ES (P less than .02) which were similar. All doses of OT increased PGE and PGF with both remaining elevated throughout the duration of the perifusion (P less than .008). However, there were no differences among doses. Release of PGE in response to OT on d 20 and 30, was higher than at ES (P less than .008). More PGF was released in response to OT from intercaruncular than caruncular tissue on d 20 (P less than .0001) and at ES (P less than .003). Release of PGF in response to OT on d 20 was higher (P less than .0001) than on d 30 and d 30 was higher than at ES (P less than .007). Basal and OT-induced release of PGE and PGF declined as day postpartum increased. We conclude that intercaruncular tissue released more PGF than caruncular tissue and both intercaruncular and caruncular tissue responded to OT with a sustained release of prostaglandins in a non-dose-dependent manner on d 20, 30 and at ES postpartum. PMID- 1862224 TI - Acute stimulatory effects of prostaglandin F2 alpha on serum progesterone concentrations in pregnant and pseudopregnant pigs. AB - The objective of this study was to investigate whether PGF2 alpha, administered to pregnant and pseudopregnant gilts in vivo, would cause an acute increase in serum progesterone concentrations prior to luteolysis. Pregnant (n = 9) and pseudopregnant (n = 4) gilts were fitted with a jugular vein cannula on day 40, were treated with 3 ml vehicle (control) i.m. on day 42 and with 15 mg PGF2 alpha on day 45. Blood samples were collected at frequent (5 and 15 min) intervals from 1 h before until 1 h after control and PGF2 alpha injections, at 15 min intervals for 4 h, and then at 5, 6, 9, 21, 33, 45 and 57 h post injection. Progesterone was measured by radioimmunoassay (RIA) in all samples. Porcine LH was measured by RIA in samples collected frequently in the 1 h pre- and 1 h post-injection periods. Serum progesterone concentrations were unchanged in both pregnant and pseudopregnant animals in response to control injection on day 42. However, in both pregnant and pseudopregnant gilts, PGF2 alpha injection on day 45 resulted in an acute increase (approximately 75-80% above pre-treatment levels; p less than 0.05) in serum progesterone lasting approximately 1 h, followed by a return to pre-treatment levels by 2 h, and then a decline to 1 ng/ml or less by 45-57 h (pregnant) or 21-57 h (pseudopregnant), associated with luteolysis. Serum LH concentrations were unchanged between 1 h pre- and post-treatment periods in response to either control or PGF2 alpha-treatment, in both pregnant and pseuodpregnant gilts. These results indicate that PGF2 alpha-injection produces a rapid and transient increase in serum progesterone concentrations which may result from a rapid and direct stimulatory action of PGF2 alpha on porcine luteal cell progesterone synthesis/secretion in vivo. PMID- 1862225 TI - Dissociation of hyperthermic and hyperglycemic effects of central prostaglandin F2 alpha. AB - We previously reported that intraventricular prostaglandins (PGs) produced hyperthermia and hyperglycemia in anesthetized rats. However, the relationship of them is little known. We examined the relationship between hyperthermia and hyperglycemia induced by intraventricular PGF2 alpha using curarized and adrenal demedullated rats. Iv curare completely prevented the PGF2 alpha-induced hyperthermia, but enhanced the hyperglycemic effect of PGF2 alpha. Adrenal demedullation completely prevented the hyperglycemia, but did not affect the hyperthermic effect of PGF2 alpha. To further assess the site of action concerned with PGF2 alpha-induced thermoregulation and glucoregulation in the central nervous system (CNS), we injected saline or PGF2 alpha into the preoptic area of the anterior hypothalamus (POA) in intact rats. After microinjection of PGF2 alpha into the POA, the rectal temperature rose, but the plasma glucose level did not increase significantly, as compared with saline-treated control rats. These results suggest that PGF2 alpha causes the central nervous system to produce hyperthermia via shivering, stimulated the somatic motor system, and to produce hyperglycemia by stimulating central sympathetic outflow to the adrenal medulla, but these operate independently under different neural regulation, and these sensitive sites are organically dissociated in the CNS. PMID- 1862226 TI - Effect of ambient oxygen changes on platelet activating factor production by fetal ovine endothelial cells. AB - To determine whether platelet activating factor (PAF) plays a role in the responses seen in the fetal and transitional circulations, we assessed endogenous release of PAF in cultured fetal ovine endothelial cells from the pulmonary artery (PA), ductus arteriosus (DA) and aorta (Ao) under basal conditions and following exposure to hypoxia or hyperoxia. The cells were prelabeled with [3H] acetate and subsequently exposed to different ambient oxygen concentrations, i.e., 95% O2 or 95% N2, balance CO2, using calcium ionophore as a positive control. The effect of indomethacin on DA endothelial PAF production following stimulation with ionophore was also established. Synthesis of [3H] PAF was measured by counts comigrating on TLC with unlabeled PAF. We found that PAF production by fetal ovine PA, Ao and DA cells was similar and unaffected by hypoxia or hyperoxia. Exposure of ionophore stimulated DA cells to indomethacin was, however, associated with a decrease in PAF production (p less than 0.05). We speculate that in vitro alterations in ambient O2 concentration do not influence fetal ovine endothelial PAF production but indomethacin may decrease PAF production in the DA. PMID- 1862227 TI - Late midtrimester medical pregnancy terminations: three different procedures with prostaglandin F2 alpha and laminaria tents. AB - One hundred twenty eight women underwent midtrimester induced abortion with: 1) combined regimen of intramniotic prostaglandin (PG) F2a injection and intracervical laminaria tents (group A, 50 women), 2) intramniotic PGF2a injection only (group B, 51 women) and 3) laminaria tents followed by intracervical PGF2a tablets insertion (group C, 27 women). The mean induction abortion time (+/- SE) was 24.9 +/- 1.7 hours for group A, 28.2 +/- 2.2 hours for group B (p greater than 0.05) and 42.1 +/- 3.4 hours for group C, significantly longer than goup A and B (p less than 0.001 and p less than 0.01 respectively). In 48 hours 98% of the patients of group A, 90% of group B (p less than 0.05) and 59% of group C (p less than 0.001) completed the abortion procedure. Parous women of group A and B presented similar induction - abortion time, while in nulliparous the use of laminaria shortened the abortion procedure significantly (p less than 0.05). The complications rate was low. In conclusion, the intracervical PGF2a insertion is a simple but very slow abortion procedure with high failure rates. The intramniotic PGF2a injection is a successful method for late midtrimester medical pregnancy termination and the concurrent use of laminaria tents shortens the abortion procedure, particularly in nulliparous, reduces the number of prostaglandins' reinjections and increases the incidence of successful abortion within 48 hours. PMID- 1862228 TI - Activity of phospholipase C in ovine luteal tissue in response to PGF2 alpha, PGE2 and luteinizing hormone. AB - Four ewes were utilized to determine the effects of prostaglandin (PG) F2 alpha, PGE2 and luteinizing hormone (LH) on activity of phospholipase C (PLC) in ovine luteal tissue. Corpora lutea were collected on d 10 post-estrus and six slices from one corpus luteum from each ewe were pre-incubated with [3H]-inositol prior to incubation with one of 6 treatments. Treatments were 1) control, 2) PGF2 alpha (100 ng/ml), 3) PGE2 (10 ng/ml), 4) LH (10 ng/ml), 5) PGF2 alpha + PGE2 and 6) PGF2 alpha + LH. Phospholipase C was determined indirectly by measuring the accumulation of [3H]-inositol mono-, bis- and tris-phosphates (IP, IP2, IP3). Effects of PGF2 alpha (0 vs. PGF2 alpha) and luteotropic treatment (0 vs. PGE2 vs. LH) and their interactions were determined by analysis of variance. There was a significant main effect of PGF2 alpha (P less than 0.01) as concentrations of IP, IP2, IP3 and total [3H]-inositol phosphates were greater in tissue slices treated with PGF2 alpha, regardless of luteotropic treatment. Within groups receiving no PGF2 alpha (1,3,4), no effect of luteotropic treatment was observed. Within groups receiving PGF2 alpha (2,5,6), LH caused a significant (P less than .05) increase in the accumulation of total [3H]-inositol phosphates. Thus, PGF2 alpha can stimulate the activity of PLC in ovine luteal tissue and LH can potentiate this effect. PMID- 1862230 TI - Naloxone-induced hypoalgesia: effects of heat, cold and novelty. AB - Experiment 1 confirmed that pairings of the opioid antagonist naloxone and a heated floor served to induce and then to maintain a conditioned hypoalgesia in rats. Experiments 2a and b demonstrated that this was not specific to some property of the heated floor: pairings of the drug and a cold floor (a) resulted in conditioned hypoalgesia and (b) maintained the hypoalgesia provoked by pairings of the drug with a heated floor. Experiments 3a and 4 showed that pairings of naloxone with the non-heated floor of the apparatus provoked hypoalgesia and provided evidence that this was due to the drug's disruption of a familiarization process. Experiment 3b revealed that pairings of naloxone with the non-heated floor maintained the hypoalgesia induced by pairings of the drug with a heated one. The results were interpreted to mean that naloxone interacts selectively with a stressor so as to maintain or enhance its aversive properties. PMID- 1862229 TI - Effect of diet on hyperthermia-induced cell lethality and prostaglandin release. AB - Hyperthermia-induced cell lethality is thought to be mediated through injury to the cell membrane. Membrane perturbation results in the release of prostaglandins (PG) and leukotrienes (LT). These compounds are potent biological mediators and may modify the tumor microenvironment and therapeutic efficacy. Membrane composition and PG/LT release are influenced by the dietary fatty acids. The relationship between these variables and response to hyperthermia was examined in vitro using murine P388 leukemia cells grown as an ascites in mice provided either saturated fatty acid diet (SFA; 16% beef tallow) or unsaturated fatty acid diet (UFA; 16% safflower oil). Cells were harvested and exposed in vitro to either 37 degrees C or 43.5 degrees C for periods up to 2 hours. Hyperthermic exposure for 2 hours resulted in 40% cell lethality in SFA cells and 55% in UFA cells. The phospholipid and total cholesterol content was higher (33% and 50% respectively) in the UFA versus the SFA cells. Hyperthermia produced a six-fold increase in prostaglandin E2 PGE2 release by SFA cells and a 4.5-fold increase by UFA cells. No LTC4 was detected. Alteration of dietary fat affects cell lethality and PG release following hyperthermic treatment. The increase in phospholipid and cholesterol content of UFA cells may be a response to reduced membrane fluidity. PMID- 1862231 TI - The art of unproven remedies. AB - Dealing with unproven treatments involves more than analyzing the available scientific data. The patient-physician relationship--the foundation of medical practice--is challenged and threatened by unproven treatments. To understand the problem, we need to understand ourselves as well as the patient and the disease. Handling the problem effectively can strengthen the patient-physician bond. PMID- 1862232 TI - Nutrition and rheumatic diseases. PMID- 1862233 TI - Alleviation of autoimmune disease by dietary lipids containing omega-3 fatty acids. AB - Dietary marine lipids that are enriched in omega-3, or n-3, fatty acids reduce the severity of autoimmune glomerulonephritis in several inbred murine strains. The protective effect of dietary n-3 fatty acids is also seen with a rat model of immune-complex induced vasculopathy, but no protective effects were seen with autoimmune vasculitis in the MRL/lpr mouse or with type II collagen-induced arthritis in rats. Dietary n-3 fatty acids are potential therapeutic agents for the treatment of autoimmune diseases, but careful clinical trials with the purified forms of n-3 fatty acids are needed to determine the usefulness of this intervention. PMID- 1862234 TI - Nutritional modulation of murine models of autoimmunity. AB - For experimental animals, calorie restriction, as well as deficits of specific nutrients, can retard the establishment and progression of autoimmune disease. The clinical value of imposed nutritional deficiencies in the treatment of autoimmune disease, however, is suspect. In contrast, diet supplementation of specific fatty acids may prove to be of value in the management of some autoimmune disorders. PMID- 1862235 TI - Food hypersensitivity. AB - Food allergy is one of several causes of adverse reactions to foods. The underlying immunologic mechanism varies from one manifestation to another, hence no current single laboratory test can be expected to be positive in every case. The diagnosis could be suggested by information gathered from the medical history or screening procedures, such as trials of elimination diets, the food/symptom diary, skin testing, and in vitro-specific IgE antibody measurement. All foods suspected by any of the aforementioned methods should be subjected to verification by appropriate elimination-challenge testing, preferably in a double blind, placebo-controlled manner. Basically, treatment is dietary elimination, and its success requires identification and avoidance of all offending foods and control of other contributory factors. PMID- 1862236 TI - An animal model of food allergic arthritis. AB - Progress in understanding rheumatoid arthritis has been slow in large part because no widely accepted animal model exists that clearly reflects naturally occurring human disease, and because the clinical expression of rheumatoid arthritis may represent multiple etiologies with shared or subtly different immunopathogenic pathways. New insights about pathogenesis and causes are needed to understand this disease and ultimately to care for patients better. PMID- 1862237 TI - Does food cause or cure arthritis? AB - Rheumatoid arthritis and most other forms of inflammatory joint disease--systemic rheumatic diseases--remain illnesses of unknown cause for which current therapy often is inadequate. The possibility that food antigens induce or perpetuate symptoms in at least some patients is novel, rational, and exciting. Studies that relate diet with arthritis might offer the potential of identifying new therapeutic approaches for selected patients and of developing new insights into disease pathogenesis. PMID- 1862238 TI - Dietary therapy for arthritis. AB - Patients believe that dietary manipulation may help their arthritic symptoms, and because they have--until recently--not felt that their doctors were interested in diet, they have been vulnerable to commercial exploitation. In the past decade, scientific studies have shown that dietary manipulation may help at least a sub group of rheumatoid patients. Mechanisms of improvement are understood incompletely, but many theories have been proposed. Further, careful studies are needed so that doctors may understand the subject and advise patients appropriately. PMID- 1862239 TI - Dietary antigens and immunologic disease in humans. AB - Absorption of small amounts of various dietary antigens in an intact state is a normal phenomenon in humans. This article discusses the normal mechanisms of excess antigen exclusion, examples of the states in which absorption can occur, and some of the immunologic consequences that have been documented. PMID- 1862240 TI - Antigens, the gastrointestinal tract, and arthritis. AB - There are a variety of forms of arthritis that appear causally related to a primary process in the gastrointestinal tract. Resolving the normal immune response to gut-acquired antigens of microbial and dietary origin can guide our understanding of the protean manifestations of the interface of arthritis and enteritis. PMID- 1862241 TI - Dietary amino acid-induced systemic lupus erythematosus. AB - The effects of dietary manipulations on autoimmune disease are understood poorly. In this article, we detail our experience with a human subject who developed autoimmune hemolytic anemia while participating in a research study that required the ingestion of alfalfa seeds. Subsequent experimental studies in primates ingesting alfalfa sprout seeds and L-canavanine (a prominent amino acid constituent of alfalfa) is presented. The results of these studies indicate a potential toxic and immunoregulatory role of L-canavanine in the induction of a systemic lupus-like disease in primates. PMID- 1862242 TI - Immunoglobulin E, mast cells, endogenous antigens, and arthritis. AB - New aspects of the biology of the mast cell and its associated products may be important to the pathogenesis of arthritis. Mast cells may be activated in human arthritides as a result of a rapidly expanding list of peptides, including cytokines and neurotransmitters. The classic immunoglobulin E-coupled mast cell activation pathways may be used in the autoimmune diseases by way of autoantibody production involving the immunoglobulin E molecule itself. This can be shown to induce mediator release in vitro. The mast cell-derived products may play a role in both the early phases of synovitis as well as the chronic destructive phase. PMID- 1862243 TI - Pseudo-food allergy. AB - This article covers the background and general concepts pertaining to pseudo allergy, the problems involved in reaching valid diagnoses of food allergy, the basics of the methodology of double-blind oral provocation, and the emotional, psychologic and recent sociologic factors particularly relevant to the inappropriate attribution of symptoms to allergy. PMID- 1862244 TI - Antirheumatic effects of fasting. AB - Total fasting induces within a few days a substantial reduction of joint pain, swelling, morning stiffness, and other arthritic symptoms in patients with rheumatoid arthritis. This remission subsides slowly after discontinuation of fasting. Its mechanisms are complex and involves diminished activation of neutrophils and lymphocytes and decreased generation of leukotrienes and of concentrations of serum complement factors, as well as of other proinflammatory systems. Moreover, ketosis and other metabolic and endocrine changes may be of significance for symptom expression and recognition. PMID- 1862245 TI - Fasting, intestinal permeability, and rheumatoid arthritis. AB - Otherwise healthy and well-nourished patients with rheumatoid arthritis show significant clinical improvement from practising prolonged fasting for 7 to 10 days. The improvement is reversible and lost when eating is taken up again. Although of little therapeutic value, the anti-inflammatory effect of short-term fasting is of significant interest and better understanding of the mechanisms is desirable. PMID- 1862246 TI - Dietary omega-3 fatty acids: effects on lipid mediators of inflammation and rheumatoid arthritis. AB - Dietary supplementation omega-3 polyunsaturated fatty acids may inhibit (at least partially) three pathways of the synthesis of lipid mediators of inflammation: the platelet-activating factor synthesis pathway, the cyclooxygenase pathway, and the 5-lipoxygenase pathway. In addition, selected cellular functions of polymorphonuclear neutrophils may be modulated by dietary fish oil. The exact mechanism of the effects of dietary supplementation with omega-3 poly-unsaturated fatty acids on these pathways is not completely elucidated; it is quite probable that the effects will vary with the duration, dose, and composition of the omega 3 polyunsaturated fatty acid preparation, with background medical therapy, and the presence of and degree of activity of the underlying inflammatory disease state. PMID- 1862247 TI - Clinical studies of omega-3 fatty acid supplementation in patients who have rheumatoid arthritis. AB - Several studies have now demonstrated reproducible clinical benefits of rheumatoid arthritis disease activity after ingestion of n-3 fatty acids. Biologic changes induced by fish oils include decreases in the production of leukotriene B4, platelet activating factor and interleukin-1. Investigations now focus on the proper dose and duration of fish-oil dietary intervention in order to obtain optimum clinical effects. Their ultimate therapeutic role has not yet been determined. PMID- 1862248 TI - Botanical lipids: potential role in modulation of immunologic responses and inflammatory reactions. AB - Enrichment of cells with fatty acids of particular botanical lipids alters cell function in vitro (for example, suppression of human synovial cell and T lymphocyte proliferation) in a manner that suggests that administration of these botanical lipids may be a useful therapeutic strategy for patients with diseases characterized by disordered immune responses and chronic inflammation. Treatment of animal models with certain plant seed oils suppresses inflammation and joint tissue injury. Controlled trials in patients with rheumatoid arthritis are in an early stage, but offer encouragement. The mechanisms whereby these novel lipids influence host defense include alteration of arachidonic acid oxygenation products and direct effects on cells independent of fatty acid metabolism. PMID- 1862249 TI - L-tryptophan-associated eosinophilia-myalgia syndrome: perspective of a new illness. AB - The current knowledge of the eosinophilia-myalgia syndrome as an evolving new disease entity is reviewed in the context of previously described eosinophilic disorders. The acute and chronic manifestations parallel the findings of the toxic oil syndrome of Spain and include scleroderma-like skin disease, neuropathy, and myopathy. PMID- 1862250 TI - American College of Rheumatology position statement: diet and arthritis. PMID- 1862251 TI - Uvulopalatopharyngoplasty in snorers with sleep apneas: predictive value of presurgical polysomnography. AB - To determine its predictive value, polysomnography was performed on 14 snorers with sleep apnea syndrome (SAS) before and 3 months after uvulopalatopharyngoplasty (UPPP). In the 8 patients considered as cured (less than 10 apneas per hour after UPPP), total apnea index (TAI) decreased from 29.7 +/- 22.6 to 4.9 +/- 3.5. Rapid eye movement sleep (REM) increased from 10.9 +/- 3.6 to 14 +/- 5.7% of the total sleep period (TSP). In the 6 uncured patients, TAI decreased from 59.7 +/- 15.7 to 32 +/- 15.7 and REM increased from 7.7 +/- 5.6 to 15.8 +/- 7.2% of TSP. Snoring and drowsiness decreased in both cured and uncured patients. A presurgical apnea index less than 40 seems to be a reliable predictor of successful UPPP. The association of obstructive apnea with either central apnea or mixed apnea was not a factor of poor prognosis. Better sleeping could explain in part the clinical improvement in both cured and uncured patients, but postoperative polysomnography is needed to detect asymptomatic SAS. PMID- 1862252 TI - Theophylline pharmacokinetics and liver function indexes in chronic liver disease. AB - Since patients with chronic liver disease present with greatly varying theophylline disposal reductions, in cirrhotics the acute theophylline dose schedule must be guided by an index of liver function that predicts theophylline pharmacokinetics. We therefore studied 26 patients with severe chronic liver disease to ascertain the efficacy of the routinely used clinical and biochemical liver function tests in predicting theophylline pharmacokinetics. The prealbumin plasma level, recently proposed as a valuable index of liver function, was also considered. With respect to 10 controls, theophylline clearance was found to be significantly reduced (30 +/- 2 vs. 75 +/- 11 ml/kg/h, mean +/- SD, p less than 0.01). However, only 7 patients had a reduction great enough to require a reduced intravenous theophylline dose schedule. An analysis of clinical utility, made on the basis of ROC curves, showed that the albumin/globulin ratio was the most effective index for identifying patients requiring lower doses of theophylline. Prealbumin and albumin were also useful, whereas bilirubin, prothrombin time, pseudocholinesterase, the presence of ascites and Pugh-Child's classification of the severity of liver disease were found to be worthless. PMID- 1862253 TI - A case of 'bronchial string'--a rare anomaly of the bronchus. AB - An incidental string-like structure spanning the lumen of the intermediate bronchus was found during bronchoscopy in an 18-year-old woman. We consider that the lesion may be a rare fibrous anomaly of the bronchus and may be closely related to a bronchial web. We have named this unusual structure 'bronchial string'. PMID- 1862254 TI - Bronchoalveolar lavage: comparison of three commonly used procedures. AB - We have studied three different lavage procedures (100, 200 and 300 ml) in patients with pulmonary sarcoidosis (stage I). The effect of bronchoalveolar lavage (BAL) on cell yield, lavage fluid recovery, dwelling time, lavage-induced arterial oxygen desaturation and occurrence of side effects was analyzed. The patients did not differ significantly in prelavage lung function and blood gas parameters. The lowest BAL return was seen in the 300-ml lavage procedure (49.5%), while the medium yielded over 70%. The lowest cell yield was seen in the BAL 100 group (10.4 X 10(6)); the highest in the BAL 300 (19.4 X 10(6)), but the latter did not differ significantly from BAL 200 (18.4 X 10(6)). Dwelling time of the fluid differed only slightly between the small and middle volume lavage (average 3.2 vs. 3.9 min p less than 0.01), but was significantly lower from the average dwelling time in the BAL 300 group (9.8 min, p less than 0.001). Arterial oxygen desaturation was lowest in the BAL 100 and most pronounced in the large volume lavage. Side effects were seen in all but 1 patient undergoing BAL 300. Cough was the most often reported side effect (9 patients); fever was observed in 6 patients, dyspnea in 4 (all undergoing large-volume lavage). Considering our results we do not think that it is justifiable to increase the volume of instilled fluid above 200 ml, because this may lead to serious side effects without increasing benefits. Using lower than 200 ml volumes decrease diagnostic yield although the risk of developing side effects is much lower. PMID- 1862255 TI - Reduction of bronchial responsiveness to methacholine after mitral valve replacement. AB - Sixteen patients with mitral valve disease, in whom bronchial hyperresponsiveness to methacholine had been detected shortly before mitral valve replacement (MVR), were reevaluated 35 +/- 1.5 months after MVR. In 9/16 patients there was a significant (greater than 1.5 fold) increase in bronchial provocation dose of methacholine (PD20FEV1) after MVR. In the same patients there was a significant increase in vital capacity (from 69.6 +/- 5 to 75.8 +/- 5.2% of predicted, p less than 0.01), a significant decrease in cardiothoracic ratio and in radiologic score for lung edema (from 64.3 +/- 2.9 to 56 +/- 2.1, p less than 0.01 and from 38 +/- 4.5 to 14.6 +/- 2, p less than 0.001, respectively). In all the patients the increase in PD20FEV1 was not related to any change in spirometric values but it was related to the decrease in cardiothoracic index (r = 0.72, p less than 0.01) and in radiologic score for lung edema (r = 0.61, p less than 0.05) observed after cardiosurgery. PMID- 1862256 TI - Circulatory response to repeated exercise in patients with chronic lung disease. AB - The pulmonary and systemic circulatory response to repeated exercise has been studied in 24 patients with chronic lung disease, mainly chronic bronchitis. The exercise consisted of supine bicycling at a constant low load (from loadless pedalling to 30 W) for 10 min with a 20 min rest period between exercises. Cardiac output was similar during the first (E1) and the second (E2) exercise periods, as well as pulmonary vascular resistance. Systemic arterial pressure, however, was lower during E2 than during E1, and this difference was significantly correlated with lung function (VC% predicted, FEV1 and FEV1% predicted) and blood gases at rest and during exercise. The patients with PaO2 below 65 mm Hg showed a larger increase in systemic arterial pressure during E1 and a smaller increase during E2 than the others. The larger increase might be due to a vasoconstrictor effect of hypoxemia and/or of the functional residual capacity increase observed in such patients with exercise. Whatever the mechanism involved, these results show that the systemic circulation is modified in patients with chronic lung disease. Results after some intervention have to be interpreted with caution if the protocol includes two exercise periods. PMID- 1862258 TI - Nocturnal hypoxia in unilateral diaphragmatic paralysis. AB - Pulmonary function has been studied extensively in patients with unilateral diaphragmatic paralysis (UDP), but there is scarce information regarding the respiratory function during sleep in this condition. We therefore studied pulmonary function in 12 patients with UDP when awake and when asleep. Diaphragmatic dysfunction was confirmed by the demonstration of low maximal transdiaphragmatic pressures in most of our patients; paradoxical gastric pressure swing was observed in 6 patients. There was a restrictive pattern in pulmonary function tests and resting arterial blood gases were rather well preserved (range SaO2 90-95%). Overnight sleep monitoring showed that the time spent in REM sleep and stage 3 and 4 sleep was reduced. The mean maximum decrease in SaO2 was 15.2 +/- 6.2% and the time with an SaO2 drop of more than 5% of the awake SaO2 was 25.4 +/- 22.8 min. None of our patients was in respiratory failure or had clinical evidence of cor pulmonale. We conclude that UDP leads to significant nocturnal hypoxemia but, in the absence of systemic lung disease, does not lead to chronic respiratory failure and cor pulmonale. PMID- 1862257 TI - Activity of erdosteine on mucociliary transport in patients affected by chronic bronchitis. AB - The influence of erdosteine (a mucomodulator endowed with mucolytic and antioxidant properties) on human mucociliary transport (MCT) was investigated in a double-blind placebo controlled study. Sixteen former smokers affected by chronic bronchitis, preselected for their mucociliary responsiveness to an inhaled beta 2-agonist, were divided into two groups (matched by number, sex, age and FEV1%) and orally treated with placebo or erdosteine (300 mg t.i.d.) for 8 days. Their MCT was assessed by the bronchofiberscopy technique just before starting the treatment and at the end of the treatment. The pretreatment mucus transport velocity in these patients was significantly decreased with respect to healthy subjects. The erdosteine treatment induced a significant improvement of MCT while placebo was inactive (mean % variation +/- SE against their baseline values being +60.4 +/- 18.4 and -3.0 +/- 5.9, respectively). This peculiar activity of erdosteine on mucus transport may be of clinical usefulness in chronic bronchitic patients and it can be added to beta 2-agonist to restore the decreased MCT. PMID- 1862259 TI - [Bibliotherapy--texts as and aide to self-help. Historical--literature review- practical application]. AB - In the following overview the term "bibliotherapy" is approached from a historical, methodical as well as practical angle in scientific literature. It is proposed to arrange different types of texts for an efficient instrumentalisation of bibliotherapeutical activities. Bibliotherapy is a good help for an overstretched medicine and can be used to improve patients compliance and self help-activities. There is a long list of essential literature attached for those who would like to learn more about this interesting new field in medical and psychosocial therapy. PMID- 1862261 TI - [Leg pain, dyspnea]. AB - A 59 year old patient with leg pain and dyspnea was hospitalized for suspected deep venous thrombosis and pulmonary embolism. The clinical, scintigraphic and radiological findings confirmed the diagnosis. Immediate therapy with heparin and oral warfarin resulted in an improvement of pain and dyspnea within a few days. The strategy for diagnostic evaluation of patients with suspected pulmonary thromboembolism is discussed. PMID- 1862260 TI - [Pharmacokinetic effects in morphine toxicity, with case examples]. AB - Three case presentations illustrate clinically relevant pharmacokinetic properties of morphine. Morphine given orally is rapidly absorbed and transformed to morphine-glucuronides (M3G, M6G) by the liver. The polar metabolites are excreted by the kidney. In chronic or acute renal insufficiency biologically active metabolites of morphine accumulate in the serum and may be responsible for severe toxic side effects. Hepatic insufficiency decreases the first-pass effect and therefore increases the bioavailability of oral morphine. This has to be considered when changing from parenteral to oral administration of morphine. PMID- 1862262 TI - [How reliable is conventional blood pressure determination? Comparison with a semi-automatic measuring device]. PMID- 1862263 TI - [What is your diagnosis?]. PMID- 1862264 TI - [Current developments in the therapy of epilepsy]. PMID- 1862265 TI - [Variable course in acute pancreatitis exemplified by case reports]. AB - The variable clinical presentation and natural history of acute pancreatitis are illustrated by case reports, namely a case with a falsely positive diagnosis of biliary pancreatitis, a case with acute interstitial pancreatitis of biliary origin, a patient with early and severe late systemic complications and with sterile necrotizing pancreatitis necessitating operative debridements twice, a patient with acute pancreatogenic ascites and ARDS requiring drainage and respiratory supportive care, a patient with biliary pancreatitis and operation for necrotizing cholecystitis, with a further, late intervention for pancreatic abscess, and a patient with internal drainage for a pseudocyst, complicated by acute biliary pancreatitis due to cholesterolosis of the gallbladder. Modern clinico-pathological classification of acute pancreatitis and modern definitions of pancreatic sepsis are important for determining prognosis and adequate treatment. PMID- 1862267 TI - [A case from practice (220). Allergic bronchopulmonary aspergillosis. Aspergilloma in the left upper lobe following chronic abscessed pneumonia. Chronic obstructive lung disease]. PMID- 1862266 TI - [Approach to the rational management of patients with dementia]. AB - In senile dementia the clinical presentation is not only determined by the mental deficits but also by affective, behavioral and somatic symptoms. Some sequelae are regularly associated with the process and the course of dementia, and therefore largely predictable and preventable. Identification of the complications commonly associated with this disease complex allows prevention and early treatment of states incriminating the natural course of the disease. By this approach a rational management of senile dementia can be achieved. PMID- 1862268 TI - [How reliable is conventional blood pressure determination? Comparison with a semi-automatic measuring device]. PMID- 1862270 TI - [Screening for colorectal cancer by determination of occult blood in the feces]. PMID- 1862269 TI - [Acute colitis: role of the clinician and place of digestive radiology]. PMID- 1862271 TI - [Interventional ultrasonography in gastroenterology has become therapeutic]. PMID- 1862272 TI - [Colitis-watery diarrhea syndrome: microscopic and collagenous colitis]. PMID- 1862273 TI - [AIDS today]. PMID- 1862274 TI - [Should one purchase a mineralometer for measuring bone mass?]. PMID- 1862275 TI - [Cardiac insufficiency: the place of transplantation?]. PMID- 1862276 TI - Epidemiology of acute respiratory infections in children of developing countries. AB - Acute respiratory infections cause four and a half million deaths among children every year, the overwhelming majority occurring in developing countries. Pneumonia unassociated with measles causes 70% of these deaths; post-measles pneumonia, 15%; pertussis, 10%; and bronchiolitis and croup syndromes, 5%. Both bacterial and viral pathogens are responsible for these deaths. The most important bacterial agents are Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. The data on bacterial etiology of pneumonia during the first 3 months of life are limited, and almost no information on the role of chlamydia and pertussis in this age period is available. The distribution of viral pathogens in developing countries can be summarized as follows: respiratory syncytial virus, 15%-20%; parainfluenza viruses, 7%-10%; and influenza A and B viruses and adenovirus, 2%-4%. Mixed viral and bacterial infections occur frequently. Risk factors that increase the incidence and severity of lower respiratory infection in developing countries include large family size, lateness in the birth order, crowding, low birth weight, malnutrition, vitamin A deficiency, lack of breast feeding, pollution, and young age. Effective interventions for prevention and medical case management are urgently needed to save the lives of many children predisposed to severe disease. PMID- 1862278 TI - Pathogenesis and sequelae of respiratory infections. AB - Bacterial pneumonia remains a major health threat, with particular risk for infants in developing countries. The effective design of strategies that minimize the morbidity and mortality from pneumonia requires an awareness of the host defense mechanisms that function to prevent respiratory infections. In this review the normal immune host defenses and the abnormalities in this process that promote the development of lower respiratory bacterial infections will be briefly reviewed. A brief discussion will focus on a complication of respiratory infections, asthma, which can follow viral illness and also be a significant problem for children. PMID- 1862277 TI - Etiology of acute respiratory infections in children in tropical southern India. AB - Nasopharyngeal secretions and throat-swab specimens from 809 children less than 6 years old with acute respiratory infection were examined by culture and indirect immunofluorescence for the presence of virus or viral antigen. Blood was cultured for the presence of bacteria in selected cases of lower respiratory infection (LRI); pleural fluid also was cultured in cases of empyema. Viruses were detected in 163 (49%) of 331 children with LRI. Respiratory syncytial virus (RSV) was the commonest agent isolated (106 children). Other viruses isolated included parainfluenza viruses (36 children), adenoviruses (12), and influenza viruses (five). Outbreaks of infection due to RSV occurred during August through October. Pneumonia was the commonest LRI encountered (178 children). Among children with pneumonia, viruses were detected in 65 (37%) of 178 children, and bacteria were isolated from 27 (18%) of the 147 children for whom blood cultures were done. Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus were the common bacterial pathogens isolated. In cases of empyema and pyopneumothorax, S. aureus was the commonest organism isolated. There were 116 children with bronchiolitis, 83 (72%) of whom had viral infections; the majority of these children (81%) had RSV infection. Croup was uncommon (eight cases) and was caused mainly by parainfluenza viruses. PMID- 1862279 TI - Pathogenesis of respiratory infections due to influenza virus: implications for developing countries. AB - The influenza viruses have an important and distinctive place among respiratory viruses: they change antigenic character at irregular intervals, infect individuals of all ages, cause illnesses characterized by constitutional symptoms and tracheobronchitis, produce yearly epidemics associated frequently with excess morbidity and mortality, and predispose the host to bacterial superinfections. Much is known about influenza viruses, but their role in respiratory infections among children in developing countries is poorly understood, and the risk factors that lead to the excess morbidity and mortality have not been identified clearly. Among the many risk factors that may be important are alterations in host immunity, malnutrition, prior or coincident infections with other microorganisms, inhaled pollutants, and lack of access to medical care. There is a great need for research that can establish more precisely the role these and other unidentified factors play in the pathogenesis of influenza infections in children in the developing world. PMID- 1862280 TI - Pathogenesis of pneumococcal pneumonia. AB - Pneumococcal pneumonia poses a serious threat to children in developing countries and remains an important disease in the industrialized world. Capsular polysaccharide is the only bacterial factor proven to contribute to pathogenesis. However, the mechanisms responsible for the hypoxemia, toxemia, crisis, and death associated with this common infection are poorly understood. Toxins secreted by the bacteria, byproducts of bacterial breakdown (e.g., pneumolysin or teichoic acid), or constituents of the intense inflammatory response in the lung might play a role in these phenomena. Malnourished children presumably carry less metabolic reserve with which they can resist the exceptional stresses of pneumococcal disease, and underlying parasitic infestation or other chronic infections, through release of potent mediators such as tumor necrosis factor or platelet-activating factor, might prime the mechanisms of host defense for a more fulminant and systemic response to infection. Vaccines that can protect infants are badly needed, and a better understanding must be gained of the mechanisms by which this pathogen continues to cause such devastating disease in the world's children and elderly. PMID- 1862281 TI - The role of Haemophilus influenzae in the pathogenesis of pneumonia. AB - Haemophilus influenzae, one of the bacteria comprising the commensal flora of the human upper respiratory tract, is also pathogenic and causes both localized and invasive (septicemic) infections. The major focus of attention and research has been on infections caused by serotype b organisms, which cause several life threatening illnesses in children, including meningitis and acute respiratory infection (ARI; e.g., epiglottitis, pneumonia). Type b polysaccharide-protein conjugate vaccines are at an advanced stage of development and implementation; however, these vaccines will not protect against noncapsulated (nontypable) strains of H. influenzae or strains expressing capsular polysaccharides other than serotype b, strains which cause a substantial proportion of ARI (especially pneumonia) among infants, particularly in developing countries. The magnitude of this problem, which contributes to many thousands-perhaps millions-of deaths each year, emphasizes the need for research on the epidemiology, pathogenesis, virulence factors, immune mechanisms, and forms of treatment relevant to ARI caused by H. influenzae in infants and implies that such studies should be given a high priority. PMID- 1862282 TI - Pertussis in developing countries: definition of the problem and prospects for control. AB - Pertussis is a distinct clinical syndrome caused by Bordetella pertussis. The disease has been well characterized and largely controlled in the industrialized countries. Studies of pertussis in developing countries have been much more limited, in large part because of difficulty in culturing the organisms. Conventional whole-cell vaccine is being widely used in developing countries but without clear epidemiologic measures of efficacy. The introduction of new acellular pertussis vaccines has focused attention on the need to define the impact of pertussis in the developing world and to explore the optimal approach to control of this illness. PMID- 1862283 TI - Pneumococcal vaccine trials in Papua New Guinea: relationships between epidemiology of pneumococcal infection and efficacy of vaccine. AB - Field trials in Papua New Guinea have shown that pneumococcal capsular polysaccharide vaccine protects children less than 2 years of age from death due to acute lower respiratory infections (ALRI). The vaccine appears to reduce mortality by preventing bacteremia. Evidence suggests that highly invasive "adult" pneumococcal serotypes are comparatively more important as a cause of ALRI in developing countries where ALRI-related mortality is higher than in North America. Capsular polysaccharide vaccines are more likely to be immunogenic for these serotypes than for the "pediatric" serotypes. The evaluation of pneumococcal vaccines in areas where mortality is high should have the highest priority. For such trials investigators should, at minimum, define epidemiologic circumstances in terms of (1) the invasive serotypes of pneumococci, (2) the protective levels of antibody, (3) the antibody response to vaccination, and (4) the general immune status of the population. PMID- 1862284 TI - Haemophilus influenzae disease and immunization in developing countries. AB - Haemophilus influenzae is one of the leading causes of severe bacterial infection in children of developing regions, causing 30% of the cases of culture-positive pneumonia and 20%-60% of the cases of bacterial meningitis. In infants and children, the majority of isolates from cerebrospinal fluid and blood and 16%-38% of pulmonary isolates are H. influenzae type b. The availability of several new polysaccharide-protein conjugate vaccines for the prevention of invasive disease due to H. influenzae type b prompts this review of the epidemiology of H. influenzae disease in the developing world and of the characteristics of current H. influenzae type b vaccines. To develop a strategy for use of H. influenzae type b vaccines in developing countries, the following data are needed: the age specific attack rates of H. influenzae type b disease and the immunogenicity and efficacy of these vaccines in young infants in developing countries. Should H. influenzae type b vaccines prove to be inadequate for the prevention of H. influenzae pneumonia, the use of non-type b H. influenzae vaccines may be necessary. PMID- 1862285 TI - The burden of acute respiratory infection due to measles in developing countries and the potential impact of measles vaccine. AB - Measles is a major cause of acute lower respiratory infection (ALRI) in developing countries. Hospital and community-based studies of ALRI have found that measles accounts for 6%-21% of the morbidity and 8%-93% of the mortality due to ALRI. Although live attenuated measles vaccine is one of the most effective vaccines in use today, measles has not been controlled in many parts of the world, primarily because the levels of vaccine coverage required to interrupt measles transmission have not been achieved. In addition, in some areas, a large percentage of cases of measles occur in infants who are younger than the age recommended for vaccination. Recent studies suggest that the Edmonston-Zagreb measles vaccine may be more immunogenic than other vaccine strains in young infants. A substantial proportion of ALRI could be prevented by increasing measles vaccine coverage and by the use of particular vaccine strains in younger children. PMID- 1862287 TI - Pathogenesis and prevention of childhood pneumonia in developing countries: recommendations. AB - Recommendations are presented that emerged from the Conference on the Pathogenesis and Prevention of Pneumonia in Children in Developing Regions held 21-23 August 1989 in Bellagio, Italy. The conference recommendations embrace three major areas: first, the biology, epidemiology, and clinical manifestation of important etiologic agents causing acute lower respiratory infection (ALRI); second, the evaluation of risk factors affecting ALRI in the developing world necessary for planning intervention strategies in diverse ecologic settings; and third, the generation of targeted research questions that will translate into available safe and effective vaccines capable of controlling ALRI-related morbidity and mortality. PMID- 1862286 TI - Control of acute lower respiratory illness in the developing world: an assessment of vaccine intervention. AB - The major bacterial and viral causes of morbidity and death due to acute lower respiratory infection (ALRI) in the developing world are amenable to control by vaccines. Initially, full use of measles, pertussis, and diphtheria vaccines, in appropriately scheduled programs, can make an immediate contribution to the reduction of severe respiratory infection. Emerging technologies offer the promise of vaccines against bacterial and viral respiratory pathogens that are suitable for infants and children in developing countries. These technologic advances include the use of protein-polysaccharide conjugates of endemic serotypes for Haemophilus influenzae and Streptococcus pneumoniae vaccines and new approaches to the use of purified protein components or attenuated live virus with respiratory syncytial virus and paramyxovirus vaccines. Such vaccines should soon be available for evaluation in developing countries. It is timely to embark upon a program of development, evaluation, and worldwide deployment of vaccines for the control of ALRI. PMID- 1862288 TI - [The reform of primary care and the development of community nursing. A new approach in the Basque country]. PMID- 1862289 TI - [Primary health care: an analysis of the nurse's work (III)]. PMID- 1862290 TI - [The effects of using the Conseal plug on physical and psychosocial variables in ostomy patients. The initial results]. PMID- 1862291 TI - [The control of the quality of care. An evaluation of results: consumer satisfaction]. PMID- 1862292 TI - [A reference standard for pediatric nursing]. PMID- 1862293 TI - [The patient, a protagonist in his own care. Ulcers and other lesions of the skin]. PMID- 1862294 TI - [Cytostatics in the hospital. All that it is important to know]. PMID- 1862295 TI - [The quality of nursing life. An indispensable condition for rendering quality care]. PMID- 1862296 TI - [The cardiorespiratory resuscitation cart]. PMID- 1862297 TI - [Diseases foretold...]. PMID- 1862298 TI - Basic studies on ursodeoxycholyl-para-aminobenzoic acid for evaluation of intestinal microflora. AB - A newly synthesized conjugate of ursodeoxycholic acid with para-aminobenzoic acid (PABA) was investigated to determine its suitability for evaluation of enteric bacteria. This compound, PABA-UDCA, was deconjugated by cholylglycine hydrolase to release free PABA, whereas it was completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In bacteriologic experiments almost all the microorganisms that split glycocholic acid deconjugated PABA-UDCA. In rat experiments urinary excretions of PABA were measured during 6 h after oral administration of 10 mg PABA-UDCA (PABA-UDCA administration test). Ten control rats excreted 338.5 +/- 13.8 micrograms (mean +/- SE) of PABA; 10 rats with intestinal stagnant loop excreted more (673.6 +/- 70.2 micrograms; P less than 0.01); whereas 10 rats in each of 7 groups pretreated with oral administration of various antibiotics excreted less (P less than 0.001; polymixin B + tinidazole, 14.0 +/- 2.5 micrograms; polymixin B, 224.9 +/- 23.5 micrograms; tinidazole, 42.7 +/- 8.6 micrograms; kanamycin, 50.3 +/- 5.8 micrograms; clindamycin, 57.4 +/- 7.4 micrograms; vancomycin, 70.4 +/- 8.5 micrograms; and paromomycin, 160.4 +/- 16.4 micrograms). This result was reflected by the bacterial mean count of feces. In the PABA-UDCA administration test, after 2 months of feeding with different diets, rats with high-fiber diet (n = 10) excreted less PABA in urine (70.9 +/- 15.9 micrograms; P less than 0.001) than rats on a control diet (n = 10) and a high-protein-high-fat diet (n = 10) (288.9 +/- 34.5 micrograms and 386.7 +/- 61.2 micrograms, respectively). Fecal bacteriologic status was consistently altered. In human volunteers 250 mg PABA-UDCA was tested. Amounts of PABA excreted in urine during 6 h after dosing were 21.11 +/- 2.02 mg in controls (n = 5) and 12.20 +/- 1.01 mg in the group treated with polymixin B plus tinidazole (n = 5; P less than 0.01). No adverse effect was observed. These basic studies indicate that this compound is likely to offer a simple and rapid method for evaluation of the intestinal microorganisms without use of radioisotopes or expensive, special equipment. PMID- 1862299 TI - Expression of HLA-DQ antigens in the small-intestinal mucosa of patients with coeliac disease. AB - Studies at the DNA and product level of B-cell lines of coeliac patients have shown a strong association between coeliac disease and the HLA-DQ alpha 2.3 and HLA-DQ beta 2.7 alleles. The monoclonal antisera SFR20-DQ alpha 5 and XIII-358.4, which specifically react with HLA-DQ alpha 2.3 and with HLA-DQ beta 2.3 and -DQ beta 2.7, respectively, have been used to detect the expression of these specificities in the small-intestinal mucosa of 7 coeliac patients and 11 non coeliac persons. An immunoperoxidase technique on frozen tissue sections of jejunal biopsy specimens was used. Positive specimens showed immunoperoxidase staining of lymphocytes and histiocytes in the lamina propria. The epithelial cells showed no immunoperoxidase staining. Positive results at the intestinal level correlated with the HLA typing of the patients and controls. The distribution found for the HLA-DQ alleles in the intestinal mucosa makes the role of a HLA-DQ alpha/beta dimer as gliadin receptor at the epithelial cell less probable, but it is compatible with the hypothesis that these DQ molecules are involved in the regulation of the intestinal immune response to gluten. PMID- 1862300 TI - 24-hour intragastric acidity and plasma gastrin during long-term treatment with omeprazole or ranitidine in patients with reflux esophagitis. AB - The reduction in intragastric acidity and the subsequent increase in plasma gastrin were compared during long-term treatment with either omeprazole or ranitidine in 19 patients with erosive reflux esophagitis. The patients received 40 mg omeprazole in the morning or 300 mg ranitidine twice daily. After healing, half the dose was given as maintenance treatment for 1 year. Intragastric acidity and plasma gastrin were measured 24 h before entry and monthly with the high dose and after 1, 6, and 12 months with the low dose. Omeprazole reduced intragastric acidity more effectively than ranitidine (p less than 0.001). This difference in efficacy was more pronounced during the daytime. Plasma gastrin increased more after omeprazole than after ranitidine (p less than 0.01), and both drugs showed a normal postprandial response and approached fasting levels before the next dose. During long-term treatment with 20 mg omeprazole in the morning no progressive alterations were observed in 24-h intragastric acidity or plasma gastrin. PMID- 1862301 TI - Effect of phlorizin on hepatic bile production before and during glucose infusion. AB - During intravenous infusion of glucose, bile secretion is reduced (cholestasis), indicating that hepatocellular metabolism of glucose could have harmful effects on the liver. Phlorizin has been identified as a compound capable of impeding glucose uptake of liver cells. To examine whether phlorizin had any effect on glucose-associated cholestasis, three groups of experiments were performed on anaesthetized pigs. In group I phlorizin (100 mg/kg body wt) during normoglycaemia stimulated bicarbonate-dependent bile secretion by 56 +/- 4%. After phlorizin, hyperglycaemia decreased both bile acid- and bicarbonate dependent bile secretion by 37 +/- 4%. But after the glucose load normalization of plasma glucose concentration increased the bicarbonate-dependent fraction by 38 +/- 4%. In group II phlorizin (100 mg/kg body wt, infused intravenously) during hyperglycaemia stimulated bicarbonate-dependent bile secretion by 35 +/- 5%. In group III bile secretion was continuously stimulated by infusion of Na taurocholate. Hyperglycaemia reduced bicarbonate-dependent bile secretion by 33 +/- 4%, but after phlorizin both bile acid- and bicarbonate-dependent bile secretion increased on average by 121 +/- 8%. The osmotic effect of hyperglycaemia cannot be blocked by phlorizin, but judged by the effect on bile secretion, phlorizin may decrease the cholestatic effect induced by metabolism of glucose. Phlorizin could be an interesting compound for use in solutions for organ preservation. PMID- 1862302 TI - Effect of insulin on hepatic bile secretion during normoglycaemia and hyperglycaemia. AB - The roles of hyperosmolality, hyperglycaemia, and insulin in glucose-induced reduction of bile secretion were examined in anaesthetized pigs. Compared with normoglycaemia, intravenous infusion of isotonic glucose reduced bile acid dependent bile secretion at a plasma glucose concentration of 18 mmol/l, with 34 +/- 4%. Lowering of plasma glucose concentration to normoglycaemia after administration of insulin (10 U/kg body wt. low dose) increased bicarbonate dependent bile secretion by 23 +/- 3%. Induction of hyperglycaemia (plasma glucose concentration, 16 mmol/l) and the combined infusion of isotonic glucose and the low insulin dose decreased bile secretion by 22 +/- 3%. During hyperglycaemia (plasma glucose concentration, 16 mmol/l) the combined infusion of isotonic glucose and a high dose of insulin (60 U/kg body wt) increased bile acid dependent bile secretion by 26 +/- 3%. Hyperglycaemia reduces bile secretion without altering plasma osmolality. Endogenous production (or too rapid degradation) of insulin may be too small during intravenous glucose infusion to cope with the metabolic demands of hepatocellular glucose conversion. This may be overcome by administration of insulin in a large dose, which stimulates bile acid secretion. PMID- 1862303 TI - Changes in gastric mucosal microcirculation and purine nucleotide metabolism during hemorrhagic shock in rats. AB - Intravital fluorescence microscopy and morphometry were used to study the microcirculation in the rat gastric mucosa during and after hemorrhagic shock. Under control conditions the circulation appeared homogeneous and unaffected by superfusion with 0.1 N HCl. During hemorrhagic shock, scattered areas of the mucosa lost circulation. Morphometry showed that the number of perfused mucosal vessels decreased significantly in the abluminal part of the mucosa both in perfused and ischemic areas, the reduction being most pronounced in the ischemic areas, where the number of perfused luminal vessels also decreased significantly. During reperfusion, bleedings occurred from the mucosa. A key finding was that the bleedings always had their origin at the border zone between ischemic and perfused areas. After hemorrhagic shock adenosine triphosphate and energy charge levels dropped significantly in both perfused and ischemic areas but with significantly lower levels in the ischemic areas. The hypoxanthine levels increased in both perfused and ischemic areas. The experiments show that local mucosal ischemia and accelerated nucleotide degradation are of pathogenetic importance in the development of stress ulcers after hemorrhagic shock. The border zone between circulated and ischemic areas seems to be an area of special interest. PMID- 1862304 TI - Factors influencing mortality from bleeding peptic ulcers. AB - The mortality, causes of death, and the factors that are influencing deaths from bleeding acute and chronic peptic ulcers were evaluated retrospectively. During a 2-year period (1986-87) 272 patients were endoscoped for acute gastrointestinal hemorrhage and were found to have bled from a peptic ulcer (chronic gastric ulcers, 90; chronic duodenal ulcers, 114; acute gastroduodenal ulcers, 66; stomal ulcers, 2). The overall mortality was 9.6% (n = 26) (gastric ulcers, 6.7%; duodenal ulcers, 11.4%; acute ulcers, 10.6%). Statistically significant factors adversely affecting prognosis for gastric ulcer were re-bleeding, need for operation and serious intercurrent illness; for duodenal ulcer were units of transfused blood, re-bleeding, signs of recent hemorrhage at endoscopy, need for operation, and serious intercurrent illness; and for acute ulcer were increasing age, shock, units of transfused blood, re-bleeding, and serious intercurrent illness. Multivariate analysis was only attempted for duodenal ulcers because of sample sizes; it suggested that active bleeding or visible vessel at endoscopy, re-bleeding, and serious intercurrent illness were independent factors for mortality. From this study it is apparent that the major determinants of a fatal outcome in bleeding peptic ulcer diseases were serious intercurrent illness and rebleeding. As it must be anticipated that patients with these particular problems are at high risk of a poor outcome, it follows that it is important they have access to skilled treatment as provided by a specialist team in an intensive care ward. It also follows that every effort should be made to keep ulcers in remission to free the ulcer patient of potentially lethal complications. PMID- 1862305 TI - The effect of omeprazole-induced hypergastrinemia on the oxyntic mucosa of mastomys. AB - Mastomys is a rodent with a high incidence of spontaneous carcinoids in the acid producing part of the stomach. The present study was conducted to examine whether hypergastrinemia could promote tumor formation in this species. Mastomys, 4 months of age, were treated for 5 months with omeprazole subcutaneously, 100 mumol/kg body weight daily, and compared with mastomys given the vehicle only. The plasma gastrin concentration and the number of antral gastrin cells were increased in the omeprazole-treated group. The hypergastrinemia was associated with elevated histidine decarboxylase activity and histamine content in the oxyntic mucosa and with a trophic effect on the oxyntic mucosa and the enterochromaffin-like cells. However, no carcinoid tumors were observed, possibly because the strain of mastomys studied does not produce carcinoids spontaneously. PMID- 1862306 TI - [The physiological significance of paranasal sinuses in man: speculations for 1800 years]. AB - The function of the paranasal sinuses has been a controversial subject since the time of Galen (130-201 AD). A review of the literature reveals quite different beliefs about their biological purpose, and eight hypotheses have received particular attention: 1) They lighten the bones of the skull; 2) improve the resonance of the voice; 3) humidify and warm inspired air; 4) increase the area of the olfactory membrane; 5) serve as shock absorbers in mechanical impacts; 6) act as thermal insulators of the brain; 7) promote facial growth and architecture; and 8) persist as evolutionary relics or faults. Scrutiny of these hypotheses shows that none has a scientific basis. PMID- 1862307 TI - [Therapy and prognosis of bacterial arthritis: a retrospective analysis]. AB - Antibiotic therapy and immediate drainage of the infected joint are established practice in the treatment of septic arthritis. The best method of drainage (repeated puncture, arthroscopy or surgical discharge) remains controversial. We analyze 34 patients with septic arthritis admitted to our hospital from 1984 to 1988. The pathogen was Staphylococcus aureus in 19 cases (56%), streptococcus in 6 (18%), pneumococcus in 2 (6%), other bacteria in (9%) and unknown in 4 (12%). In 62% the infection was blood-borne. The knee was affected in 12 cases (35%) and the shoulder in 10 (30%). A preceding joint puncture was the main source of infection. In 24 patients (70%) the initial joint drainage was by repeated puncture, while in 10 cases (30%) surgical drainage was the initial treatment. In 11 of the 24 patients initially treated by repeated puncture, surgical drainage was needed in the course of treatment because of persistent local infection of the joint. In only 13 (39%) was "medical" treatment alone effective. 5 patients died (14.7), 3 (8.8%) due to the infection. All deaths occurred in the "medical" group. 21 patients were asked about symptoms in the affected joint. In 71% there were no problems or only minimal ones, while in 29% there were distinct problems. 5 of the 6 patients with severe symptoms had been treated by repeated puncture. We conclude that surgical drainage of an infected joint is prescribed too rarely in departments of rheumatology and internal medicine. Arthroscopic or surgical drainage is indicated in cases of coxarthritis, omarthritis, in cases where symptoms last longer than 7 days and in patients with severe sepsis. PMID- 1862308 TI - [Radiation burden of organs in fluoroscopic studies]. AB - Various conventional and modern fluoroscope units had been examined with an anthropomorphic phantom to determine the applied average organ doses. The aim of our investigation was to compare these doses with those normally delivered to the patients during a conventional X-ray examination of the thorax. As was to be expected, the doses resulting from conventional fluoroscopic units are much higher than the doses from modern units. As shown by means of our measurements, the efforts of advanced technology permit to reduce the dose rate up to a factor of 30. I.e., the doses resulting from modern fluoroscopic units are even smaller than the doses received during a conventional thoracic X-ray examination, what means a great improvement for this examination technic. PMID- 1862309 TI - [Angioedema due to acquired complement-C1-inhibitor deficiency in a female patient with non-Hodgkin lymphoma and autoimmune hemolytic anemia]. AB - A case of angioedema due to acquired deficiency of the regulatory protein C1 esterase-inhibitor (C1-INH) is reported. The edematous attack occurred 3 1/2 weeks after initiation of successful therapy for autoimmune-hemolytic anemia in the course of long-standing non-Hodgkin's lymphoma. At the time of acute edema the complement profile was typical: virtual absence of C1-INH function was associated with diminished concentrations of the components of the classical pathway of complement (C1q, C1r, C1s, C2, C4) and reduced complement hemolytic activity (CH50). Anti-C1-INH-autoantibodies were not detected. The angioedema lasted for about one week, and no further attacks occurred during the five-months follow-up period. Although there was only a minor adjustment to the therapy, the C1q, C2, C4 and CH50 values gradually increased to levels close to the lower limit of the normal range, while C1r and C1s showed normal values. In contrast to most other reports, this case was characterized by angioedema which was precipitated only after initiation of appropriate treatment for the underlying disease rather than before therapy or even diagnosis of the underlying disease. PMID- 1862310 TI - [The fate of Warren's splenorenal shunt in the era of sclerotherapy]. AB - From 1969 to 1990, 52 patients underwent splenorenal shunt after one or more esophageal variceal hemorrhages. Sixty days' mortality was 15.4% (8 deaths). 3 patients were lost to follow-up soon after hospital discharge. The remaining 41 patients could be followed for 5.5 years on average: 26 died, 3 were lost to follow-up late after discharge and 12 are presently alive. Only 4 of the followed up patients suffered recurrent bleeding due to a thrombosed shunt. Temporary mental disturbances were noted in 4 cases but no incapacitating encephalopathy was recorded. In the last 10 years, performance of the Warren shunt has decreased strikingly as a result of the increasing popularity of endoscopic sclerotherapy. Surgical and anesthetic techniques have, however, improved too, resulting in a lower morbidity and mortality rate. Recurrent bleeding and neurological sequelae being rare, we conclude that distal splenorenal shunt remains a valuable alternative to long-term sclerotherapy in selected cases. PMID- 1862311 TI - [The value of computerized tomography and endoscopic retrograde cholangiopancreatography in the assessment of malignant jaundice]. AB - US and direct cholangiography have considerably simplified the diagnostic workup of mechanical icterus. These procedures allow diagnosis of choledocholithiasis in most cases. We analyze the possible additional role of CT in the diagnostic workup of malignant jaundice in a retrospective study. Between January 1986 and December 1989. ERCP was performed in 37 patients with malignant jaundice. 21 of the lesions were located in the pancreas, 7 in the papilla and 6 in the bile duct; in 2 cases the choledochus was compressed by metastases and in one chronic pancreatitis was present. In 34 of 37 patients (92%), ERCP alone permitted a definite diagnosis. 22 patients underwent CT as the primary diagnostic procedure. In only 9 of these (41%) was an unequivocal diagnosis possible, as opposed to ERCP (19 of 22 or 86%). No complications of ERCP were observed. We therefore conclude that the diagnosis of malignant jaundice can be based on history, physical examination, laboratory results, US and ERCP alone. In the vast majority of cases CT is unnecessary. PMID- 1862312 TI - [Well-differentiated papillary mesothelioma of the peritoneum. Rare, but prognostically important differential diagnosis]. AB - A 35-year-old man who presented with ascites and multiple small peritoneal nodules is still in good health after a follow-up of 6 years despite the fact that two different former histologic sections were interpreted as malignant mesothelioma. The present histologic finding is a well differentiated papillary mesothelioma. We review the literature and discuss the significance of this uncommon finding. It is generally associated with an excellent prognosis. Chemotherapy should be withheld. PMID- 1862313 TI - [The prognostic value of the serial determination of galactose elimination capacity in chronic active hepatitis]. AB - The prognostic value of different conventional liver tests was compared with that of the galactose elimination capacity (GEC) in 37 patients with chronic active hepatitis. During a mean observation period of 4.5 years, 12 patients died of the disease. None of the conventional liver tests (transaminases, prothrombin time, albumin, Child-Pugh classification) discriminated between survivors and nonsurvivors. In contrast, GEC discriminated between survivors and nonsurvivors (p less than 0.04). The best prognostic criterion was a decrease in GEC, since only patients with a decrease died of the disease. The positive and negative predictive values of this criterion were 100 and 60% respectively. This concept could prove useful for stratification purposes in therapeutic trials, as well as in assessment of novel forms of treatment of chronic active hepatitis. PMID- 1862314 TI - [Effects and side effects of a 1-year treatment of primary hypercholesterolemia with simvastatin]. AB - The HMG-CoA-reductase inhibitors lovastatin, pravastatin and simvastatin (statins) represent a new group of drugs for the treatment of hypercholesterolemia. The present study was performed with simvastatin, the first statin introduced in Switzerland, and involved 46 patients with primary hypercholesterolemia during one year. The dose of simvastatin was adjusted according to the serum cholesterol level; during treatment with 10, 20 and 40 mg, total cholesterol was lowered by 18, 26 and 27% respectively and LDL cholesterol by 27, 38 and 35% respectively, after one year. A combination of 40 mg simvastatin with a bile acid sequestrant or a nicotinic acid derivative resulted in a cholesterol lowering of 38% and an LDL lowering of 48% respectively. The serum triglycerides decreased only at a dose of 10 mg. The changes in LDL and HDL cholesterol were accompanied by parallel alterations in apoprotein B and A1 concentrations. Although none of the patients showed a significant increase (greater than 3 x UNL) in serum ASAT, ALAT or CK, all these values increased slightly but significantly. Tolerance of the drug was otherwise excellent; gastrointestinal side effects were only rarely reported. Therefore, simvastatin is an effective and well tolerated cholesterol-lowering drug. Whether prevention of coronary heart disease is possible, however, is not yet proven. PMID- 1862315 TI - [Continence-preserving proctocolectomy using an ileum-pouch-anal anastomosis]. AB - Between 1985 and 1990 restorative proctocolectomy with ileo-anal anastomosis was performed in 19 patients (in 15 cases for ulcerative colitis, in 2 cases for familial adenomatous polyposis and in 2 cases for multiple synchronous colorectal carcinomas). Restoration of intestinal continuity was performed by ileo-anal J pouch (j-shaped ileal reservoir) by the method of UTSUNOMIYA. Eleven patients were operated upon in a two-stage procedure and 8 patients in a three-stage procedure. There was no mortality and no pouch had to be removed. Mean bowel frequency is 5-6 times during daytime and 0-once during nighttime, a fact which speaks for the excellent quality of life in these patients. PMID- 1862318 TI - ["Prevalence of toxoplasmosis infestation, congenital infection risk and developments in Geneva from 1973 to 1987" by J.E. Bornand and J.D. Piquet, Schweiz. med. Wschr. 1991; 121: 21-29]. PMID- 1862317 TI - [Primary malignant non-Hodgkin lymphomas of the digestive tract: the role of surgery]. AB - Forty-two patients with non-Hodgkin's malignant lymphoma (NHML) of the gastrointestinal tract were operated on between 1971 and 1989. NHML was located in the stomach in 23 (55%), in the small bowel in 16 (38%), and in the colon in 3 (7%). One-fourth of patients were hospitalized with an acute abdomen and had to undergo emergency surgery. Preoperative diagnosis was obtained in 40% of cases only. Since 1986, however, and thanks to immunohistochemistry, gastroscopy was able to diagnose gastric NHML in 10 of 11 cases. Twenty-six patients (62%) underwent curative surgery. Operative mortality was 11.9%, 42% in case of emergency surgery, but mortality was nil after elective procedures. Half the patients had no further treatment. Five-year survival was 67%. Except for the mucosa associated lymphoid tissue (MALT) tumors, histopathological characteristics had less influence on prognosis than expected. On the other hand, prognosis was significantly better after curative surgery (p less than 0.001). PMID- 1862320 TI - Treatment of acute knee injuries with anterior cruciate lesions (ACL injuries). PMID- 1862316 TI - [Fecal occult blood--does a hemoglobin-specific tests improve the diagnosis of relevant colonic neoplasms?]. AB - The object of this study was to assess whether an immunological test specific for human hemoglobin improves the detection of bleeding from colorectal tumors as compared to a conventional guaiac test for occult fecal blood. We examined one stool sample from 134 patients prior to a complete colonoscopy by the Colo-Immun Test (CI) as well as the Colo-Rectal-Test (CR). CI proved to have a higher sensitivity for occult bleeding from all colonic lesions, but this difference was not statistically significant. There was, however, no difference in the sensitivity of the two tests in detecting bleeding from relevant colonic neoplasms. In this study the immunological CI did not improve the detection of occult fecal blood loss due to adenomas and carcinomas of the colon in comparison with CR. PMID- 1862319 TI - [Prevention of serious injuries due to bicycle riding]. AB - In 1984 there were 32,860 persons who suffered from bicycle-related injuries in Switzerland. They accounted for 27% of the persons injured on the road. Cranio cerebral trauma had to be treated in 26% of the injured bicyclists. Two thirds of hospital admissions after bicycle accidents were due to head injuries. Craniocerebral trauma accounted for about 65% of the residual lesions and for 69% of the lethal injuries related to bicycle accidents. A relatively simple and effective protection for these injuries would consist of the use of a helmet. To estimate the expected reduction of head injuries if everybody had a helmet, the regression analysis of a previous study from Seattle was applied. By wearing hard shell helmets, there would be a reduction in number and severity of 7500 head injuries and a decrease of 2000 hospital admissions each year in Switzerland. In addition to the decrease in suffering and quality of life of the use of helmets would lower health costs by at least 22 million swiss francs per year. PMID- 1862321 TI - [The effect of supramaximal exercise on the recovery kinetics of lactate]. AB - Blood lactate recovery curves from muscular exercise can be described by a sum of two exponential terms consisting in a rapidly increasing and a slowly decreasing component. A two-compartment model consisting of the previously working muscles and the remainder of the lactate space furnishes the simplest but nevertheless realistic explanation of this evolution pattern. The velocity constants of the rapidly increasing (gamma 1) and the slowly decreasing (gamma 2) components inform respectively on the abilities of the body to exchange and remove lactate. However the blood lactate recovery curves observed in three untrained subjects after 3-min 107-115% VO2max cycling display a transitory plateauing of the lactate concentration between the increasing and decreasing phases of the curves. This levelling off of the concentrations at their highest value was not observed in an endurance trained subject after a 3-min 107% VO2max exercise. Despite the plateauing and consequent less good fit than to the usual evolution curves, the recovery curves could still be accurately fitted by the biexponential time function. After supramaximal exercise the abilities to exchange and to remove lactate are severely impaired. These impairments in the functional properties of the organism are very likely associated with and/or linked to physico-chemical modifications which have been observed as much at the cellular level as in the body fluids during and after supramaximal exercise. PMID- 1862322 TI - [Bronchial asthma in high-performance athletes]. AB - Bronchial asthma is as frequent among high performance athletes as in the general population. We requested information from 2961 athletes of national or international level about these matters and received 2060 answers. From these, we identified 146 athletes (7.1%) with exercise-related deep respiratory airways symptoms. Athletes subject to hay fever (42%) suffer significantly more often (p less than 0.001) from such symptoms during exercise. 80% of these 146 cases had an insufficient diagnostic investigation and/or were treated with medicines unsuited to their needs or even not treated at all. Of particular interest, athletes who additionally had hay fever also received inadequate treatment, even though it is well known that they are subject to enhanced bronchial irritability during the pollen season. As a rule, athletes with exercise-related respiratory problems should be advised to abstain from smoking, especially if they suffer from an atopy-like illness, such as hay fever. PMID- 1862323 TI - [Accidents in delta sailing]. AB - We interviewed a group of 259 deltasailors about their injuries which befell them in Switzerland during their sports activity. They reported on 257 incidents, 8% of which were contusions and 24% resulted in fractures. 70% of all injuries affected the arms or legs, whereas 30% were located on the head or trunk. An accident occurred far more often during the landing phase (72%) than at take-off (28%). The mean hospital stay was noticeably longer for injured women (15 days) than for men (8 days). PMID- 1862325 TI - Not so stupid. PMID- 1862324 TI - Hard to swallow? PMID- 1862326 TI - Painkiller. There's still room for luck in industrial chemistry. PMID- 1862327 TI - Exporting misery. A U.S. abortion ruling affects women's health worldwide. PMID- 1862328 TI - Do DNA fingerprints protect the innocent? PMID- 1862329 TI - Positive response. Encouraging results in the search for an AIDS vaccine. PMID- 1862330 TI - Man's best friend. Veterinary research provides clues to human diseases. PMID- 1862331 TI - The human telomere. PMID- 1862332 TI - Biosensors. PMID- 1862333 TI - Antichaos and adaptation. PMID- 1862334 TI - HIV research and nef alleles. PMID- 1862335 TI - OSI investigator "reined in". PMID- 1862336 TI - Images of conflict: MEG vs. EEG. PMID- 1862337 TI - Report card on the genome project. PMID- 1862338 TI - A unique lab design fits the British to a tea. PMID- 1862339 TI - Small is beautiful: microlivestock for the Third World. PMID- 1862340 TI - New 3-D protein structures revealed. The shape of cholera. PMID- 1862341 TI - First protein kinase structure. PMID- 1862342 TI - Crystal structure of the catalytic subunit of cyclic adenosine monophosphate dependent protein kinase. AB - The crystal structure of the catalytic subunit of cyclic adenosine monophosphate dependent protein kinase complexed with a 20-amino acid substrate analog inhibitor has been solved and partially refined at 2.7 A resolution to an R factor of 0.212. The magnesium adenosine triphosphate (MgATP) binding site was located by difference Fourier synthesis. The enzyme structure is bilobal with a deep cleft between the lobes. The cleft is filled by MgATP and a portion of the inhibitor peptide. The smaller lobe, consisting mostly of amino-terminal sequence, is associated with nucleotide binding, and its largely antiparallel beta sheet architecture constitutes an unusual nucleotide binding motif. The larger lobe is dominated by helical structure with a single beta sheet at the domain interface. This lobe is primarily involved in peptide binding and catalysis. Residues 40 through 280 constitute a conserved catalytic core that is shared by more than 100 protein kinases. Most of the invariant amino acids in this conserved catalytic core are clustered at the sites of nucleotide binding and catalysis. PMID- 1862343 TI - Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. AB - The structure of a 20-amino acid peptide inhibitor bound to the catalytic subunit of cyclic AMP-dependent protein kinase, and its interactions with the enzyme, are described. The x-ray crystal structure of the complex is the basis of the analysis. The peptide inhibitor, derived from a naturally occurring heat-stable protein kinase inhibitor, contains an amphipathic helix that is followed by a turn and an extended conformation. The extended region occupies the cleft between the two lobes of the enzyme and contains a five-residue consensus recognition sequence common to all substrates and peptide inhibitors of the catalytic subunit. The helical portion of the peptide binds to a hydrophobic groove and conveys high affinity binding. Loops from both domains converge at the active site and contribute to a network of conserved residues at the sites of magnesium adenosine triphosphate binding and catalysis. Amino acids associated with peptide recognition, nonconserved, extend over a large surface area. PMID- 1862344 TI - The 2.3 angstrom X-ray structure of nitrite reductase from Achromobacter cycloclastes. AB - The three-dimensional crystal structure of the copper-containing nitrite reductase (NIR) from Achromobacter cycloclastes has been determined to 2.3 angstrom (A) resolution by isomorphous replacement. The monomer has two Greek key beta-barrel domains similar to that of plastocyanin and contains two copper sites. The enzyme is a trimer both in the crystal and in solution. The two copper atoms in the monomer comprise one type I copper site (Cu-I; two His, one Cys, and one Met ligands) and one putative type II copper site (Cu-II; three His and one solvent ligands). Although ligated by adjacent amino acids Cu-I and Cu-II are approximately 12.5 A apart. Cu-II is bound with nearly perfect tetrahedral geometry by residues not within a single monomer, but from each of two monomers of the trimer. The Cu-II site is at the bottom of a 12 A deep solvent channel and is the site to which the substrate (NO2-) binds, as evidenced by difference density maps of substrate-soaked and native crystals. PMID- 1862345 TI - Solution structure of kistrin, a potent platelet aggregation inhibitor and GP IIb IIIa antagonist. AB - The structure of kistrin, which is a member of a homologous family of glycoprotein IIb-IIIa (GP IIb-IIIa) antagonists and potent protein inhibitors of platelet aggregation, has been determined by two-dimensional nuclear magnetic resonance (NMR) spectroscopy. The 68-residue protein consists of a series of tightly packed loops held together by six disulfide bonds and has almost no regular secondary structure. Kistrin has an Arg-Gly-Asp (RGD) adhesion site recognition sequence important for binding to GP IIb-IIIa that is located at the apex of a long loop across the surface of the protein. PMID- 1862346 TI - Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. AB - Malignant hyperthermia (MH) causes neurological, liver, and kidney damage and death in humans and major economic losses in the swine industry. A single point mutation in the porcine gene for the skeletal muscle ryanodine receptor (ryr1) was found to be correlated with MH in five major breeds of lean, heavily muscled swine. Haplotyping suggests that the mutation in all five breeds has a common origin. Assuming that this is the causal mutation for MH, the development of a noninvasive diagnostic test will provide the basis for elimination of the MH gene or its controlled inclusion in swine breeding programs. PMID- 1862347 TI - Interventions in renal scintigraphy. AB - Physiological and pharmacological intervention for the purpose of determining organ functional reserve is a familiar concept in medical testing and in nuclear medicine. Nephrourologic applications include established procedures such as diuretic scintigraphy for determination of urinary outflow obstruction and captopril scintigraphy for determination of renovascular hypertension. Subtle renal dysfunction may exist among some individuals with essential hypertension, induced by provocative exercise renography, and not observed at rest. The strength of nuclear medicine resides in its ability to assess disorders of organ function for the diagnostic, prognostic, or pathophysiological information provided. Nephrourologic interventions are reviewed with an emphasis on the functional changes caused by the intervention. PMID- 1862348 TI - Augmented cholescintigraphy: its role in detecting acute and chronic disorders of the hepatobiliary tree. AB - Cholecystagogue cholescintigraphy can be employed as a means of (1) confirming the surgeon's and/or gastroenterologist's clinical impression of symptomatic chronic acalculous biliary disease, (2) better understanding the pathophysiology of gallbladder disease, (3) preparing patients for hepatobiliary scintigraphy who have fasted for longer than 24-48 hours and who are suspected of acute cholecystitis, and (4) reducing the time required to confirm the clinical impression of acute cholecystitis. Morphine-augmented cholescintigraphy is also used to decrease the time required to determine cystic duct patency. Phenobarbital-augmented cholescintigraphy is used as a means of increasing the accuracy of hepatobiliary scintigraphy in differentiating neonatal hepatitis from biliary atresia. Nonpharmacological interventions and augmentations have been employed to maintain the high degree of accuracy of cholescintigraphy in confirming the clinical impression of acute cholecystitis. The efficacy of these modalities in detecting acute and chronic disorders of the hepatobiliary tree as well as how and why they are performed comprise the contents of this article. PMID- 1862349 TI - Physiological and pharmacological interventions in radionuclide imaging of the tubular gastrointestinal tract. AB - Radionuclide studies of the gastrointestinal tract (GI) are used to measure GI function and to detect anatomic lesions such as Meckel's diverticuli. A variety of physiological and pharmacological interventions have been applied to both types of studies to gain a better understanding of GI function and to improve detection of disease. This article will review interventions useful in imaging the tubular GI tract. Discussed are the measurement of GI motility and function by gastric emptying and imaging studies for GI bleeding including the Meckel's scan. Interventions involving the hepatobiliary system are covered elsewhere in this issue. PMID- 1862350 TI - Interventions and functional brain imaging. AB - Assessment of regional cerebral blood flow (rCBF) is useful in the evaluation of cerebral vascular disease. However, a single resting study has limitations in that a normal rCBF may be present with diminished cerebral vascular flow reserve and regions of decreased rCBF may be seen with diaschisis or selective neuronal loss and an intact vascular supply. To help differentiate these conditions a stress rCBF study can be obtained following the administration of vasodilatory stimulus. The topic of this review is the discussion of single photon emission computed tomography (SPECT) and vascular intervention, primarily, acetazolamide (Diamox, Lederle Laboratory Division, Pearl River, NY) augmented SPECT in the evaluation of cerebral vascular disease. PMID- 1862351 TI - Radionuclide studies in impotence. AB - Impotence may be of physiological origin with causes including vascular or neurological pathology. Alternatively, it may be of psychogenic origin. Clinicians can distinguish between psychological and organic impotence by observing nocturnal penile tumescence. Non-radionuclide investigations for organic impotence include penile plethysmography or pulse Doppler analysis for arterial supply, cavernosometry for venous drainage, and biothesiometry or evoked potentials for neurological pathology. Radionuclide studies are primarily based on the use of technetium 99m-pertechnetate, 99mTc-red blood cells, or xenon 133 to study the blood flow, with or without pharmacological intervention, commonly papaverine. PMID- 1862352 TI - Arterial thrombosis and insufficiency causing diffusely decreased uptake by skeleton of a limb. PMID- 1862353 TI - "Missing" one kidney. PMID- 1862354 TI - Pharmacological and other nonexercise alternatives to exercise testing to evaluate myocardial perfusion and left ventricular function with radionuclides. AB - Pharmacological vasodilatation with either dipyridamole or adenosine is a safe and accurate alternative to exercise testing to diagnose coronary artery disease with thallium 201 myocardial perfusion imaging. The technique also provides important prognostic information with regard to future cardiac events in patients undergoing diagnostic testing, in those evaluated preoperatively, and in those with recent myocardial infarctions. Multigated equilibrium and first-pass radionuclide ventriculography also are well suited to evaluate the effects of interventional procedures. Success has been achieved using this methodology in a variety of interventions including conventional exercise testing, pharmacological stress testing, atrial pacing, assessment of myocardial viability with nitroglycerin, mental stress testing, and ambulatory monitoring of left ventricular ejection fraction. PMID- 1862355 TI - Surgical pathology of carcinoma of the colon and rectum. PMID- 1862356 TI - New hope and promise for sphincter preservation in the management of cancer of the rectum. PMID- 1862357 TI - [Organizational and methodological conditions for rendering medical services to young children with respiratory diseases]. PMID- 1862358 TI - [Improving the quality control of health care]. AB - The problem of raising the quality and effectiveness of medical care in the agricultural region of the country is being considered from the point of view of systems approach where a priority is given to the formation of a common modern scientific technology of delivering medical care different from feldsher midwifery units to specialized centres. Three years period of introducing the system of improving the management of quality and effectiveness of medical care delivery resulted in reduction of morbidity associated with temporary and persistent disability from respiratory diseases, reduction of mortality from circulatory diseases in working age population. PMID- 1862360 TI - [Morbidity and the ways of improving the organization of medical services to the victims of the accident at the Chernobyl nuclear power plant]. PMID- 1862359 TI - [Hypertension: economic aspects]. AB - The data are provided on the economic losses caused by hypertonic disease (HD) to the national economy of Lithuania in 1980 which are estimated as the sum of money spent by the state on curative and preventive measures and economic losses due to temporary disability, invalidity and premature deaths. Economic losses including damage caused by temporary disability, invalidity and premature deaths accounted for 11.1 million roubles. The major losses were caused by temporary disability. They topped the economic damage due to premature deaths by more than two times. State expenditures on curative and preventive care for hypertonic patients in the structure of economic losses accounted for only 10.6%. PMID- 1862361 TI - [Causes of injuries in agriculture and the concepts of their prevention]. PMID- 1862362 TI - [Morbidity among children attending preschool institutions]. AB - The paper provides data on children morbidity in departmental preschool institutions during nine years period (1981-1989) and labour losses due to the care for sick children. The pattern of general morbidity, dispensary group, classification of children by groups of health are provided. Health-promoting activities for frequently ailing children are described, their effectiveness as to the level of reducing morbidity is shown. The further stage of improving the work on health promotion is the construction of children's curative and health promoting complex staffed with 43.5 persons. PMID- 1862363 TI - [Comparative analysis of various types of vocational rehabilitation of convalescents in a workshop health unit]. AB - The paper provides the results of the examination of 112 convalescents of different age using the method of determining the class of ability to work according to the response to the active orthostatic test. A comparative analysis was conducted of different methods of occupational rehabilitation under conditions of workshop medical unit of a large industrial enterprise. It was found that the most effective method is the transfer of convalescents to a more easy work for physiologically substantiated periods of time. Validated criteria of assessing the efficacy of rehabilitation measures are proposed. PMID- 1862364 TI - [Prevention of injuries: technological principles]. AB - The principles of modern technology in injuries prevention have been elaborated which are based on fundamentally new approaches to the interpretation of injuries and classification of prevention activities proposed by the author. It is emphasized that each type of prevention (urgent, operative, planned) corresponds to a certain technological succession of operations: selection and pickup of information, the time period and mechanism of analysis communication, etc., and also to specific goals. A model of injuries prevention system is proposed which is based on organizational structures of local councils of people's deputies and may be used for any administrative territory of the country with due regard for peculiarities and specific factors determining the level and nature of injuries. PMID- 1862365 TI - [Socio-hygienic aspects of preparation of schoolchildren for family life]. AB - The article provides the research findings on the training of schoolchildren in family life within the limits of school education (training course on "Ethics and psychology of family life"). Organisational issues are described, shortcomings are revealed. By means of anonymous questionnaire survey of schoolchildren their awareness of different aspects of family life, the sources of information, the role of school and health workers in conducting this work among pupils, etc. is detected. Validated proposals on improving the preparedness of schoolchildren for family life, health protection in marriage, ensuring healthy progeny are provided. PMID- 1862366 TI - [A team method of work organization]. PMID- 1862367 TI - [Activities of the Research Society for Health Economics in the People's Republic of China]. PMID- 1862368 TI - [Yugoslavian experience with the development of public health]. PMID- 1862369 TI - [Problems of medicine in the works of M.V. Lomonosov (1711-1765)]. PMID- 1862370 TI - [Hyaluronic acid and hyaluronidase in influenza]. AB - Hyaluronidase and hyaluronic acid activities are markedly changed in influenza, these changes directly depending on the severity of the inflammatory process that depends on the presence of bacterial complications in influenza. The authors' findings correlate with the literature data on the blood mucolytic system status in various infectious diseases. The results recommend measurements of hyaluronidase and hyaluronic acid activities as an additional test for the early diagnosis of influenza complications. PMID- 1862371 TI - [Current clinico-pathogenetic aspects of chronic hepatitis B]. AB - The author analyzes the results of clinical morphologic and immunologic studies carried out in 55 patients (78.2 percent of these with chronic active hepatitis, 12.7 percent with chronic latent hepatitis, and 9.1 percent with chronic passive hepatitis) with the virus replication phase serum markers and in 57 patients (82.5 percent with chronic passive and 17.2 percent with chronic active condition) with the hepatitis B virus integration phase markers. Histologic examination of the liver has revealed hepatocyte necroses, lobular necroses predominating in the patients with the replication phase markers (90.9 percent) and periportal necroses in those with the integration phase markers (17.5 percent). Clinical symptoms and laboratory findings, irrespective of the stage of hepatitis B virus, were not representative. Chronic hepatitis associated with the viral replication stage, was characterized by a reduction of T lymphocyte functional activity, elevation of T suppressor count, and reduced immunologic regulation index. In-Chronic hepatitis associated with viral integration phase the immunologic parameters did not much differ from those in the controls. The results evidence that the dialogic cycle of hepatitis B virus development plays the major role in the pathogenesis of chronic hepatitis; active stage of the disease is associated with the replicative phase of viral development and regressive stage and arrest of the condition with the integration phase. PMID- 1862372 TI - [The role of staphylococcal superinfection in viral hepatitis]. AB - Viral hepatitis A was diagnosed in 69.35 percent of the 124 patients with viral hepatitides aged 15 to 62, 54.1 percent of these females and 45.9 percent males, and viral hepatitis B in 30.65 percent. The disease course varied in severity, was typical in all cases; the icteric form was observed in all the patients. An unfavorable pyoinflammatory premorbid background was present in 1/3 of the examinees. The studies have revealed that a staphylococcal superinfection with the icteric syndrome contributed to the pathogenesis of viral hepatitis. Antistaphylococcal agglutinins were detected in 65.6 percent of hepatitis A and in 73.7 percent of hepatitis B patients, and alpha antitoxins in 81.1 and 71.0 percent of patients, respectively. The disease severity correlated with high antitoxin titers, high antitoxin titers with a delayed convalescence of viral hepatitis A patients. Changes in the titers of antistaphylococcal agglutinins in hepatitis B patients were not rapid and their time course correlated with the terms of liver function recovery. The author comes to a conclusion that bacterial superinfection contributes to the pathogenesis of viral hepatitides, staphylococcal infection among other ones, that essentially influences the disease course. PMID- 1862373 TI - [Dynamics of immunologic indicators in children with severe forms of suppurative septic diseases after the exchange-substitute plasmapheresis]. AB - Time course of the immunity system parameters was followed in children suffering from grave endotoxicosis forms treated by discrete plasmapheresis (DPA) as the emergency therapeutic measure. T, T-active, B lymphocytes, O cells, immunoglobulins A, G, M were analyzed, as were the counts of phagocytizing leukocytes and circulating immune complexes. The infectious process was found to lead to a temporary relative secondary immunodeficiency. DPA with perfusion of hyperimmune plasma resulted in rapid correction of all component of the immunity system, paralleled by normalization of the general clinical status of the patients, and prevented chronic transformation of the process. PMID- 1862374 TI - [Treatment of varicose veins]. AB - The authors analyze the results of treatment of 1500 patients suffering from varicose conditions. They have developed original methods for the treatment of varicose dilatation of subcutaneous veins: endovascular and ++perivascular electrocoagulation of subcutaneous veins, removal and crossing of subcutaneous and communicant ++ veins with vein extractor and capron fish line; liquidation of venous conglomerates by means of a submerged removable suture; ++supra-fascial crossing of subcutaneous veins. Employment of these methods in combination with the traditional treatment modalities yields a good therapeutic and cosmetic effect. The methods are simple and available, this recommending them for any surgical hospital. PMID- 1862375 TI - [Natural anti-PGF2alpha and anti-PGE2 antibodies in ischemic heart disease and hypertension]. AB - The important role played by prostaglandins in the pathogenesis of coronary disease and essential hypertension is well known. The authors have attempted to reveal a relationship between blood levels of natural autoantibodies to PGF2 alpha and PGE2 and specific features of coronary disease and essential hypertension course and complications. A total of 87 subjects were examined, 23 of these--normal controls, 25 patients with myocardial infarction, 22 with angina pectoris, and 17 with essential hypertension. Solid-phase enzyme immunoassay was employed to detect anti-PGF2 alpha and anti-PGE2 antibodies. These antibodies were found in normal subjects, coronary patients and hypertensives. Blood levels of these antibodies correlated with some complications of coronary disease and essential hypertension. These results permit a hypothesis that the pathogenetic physiologic role of the detected natural antibodies to prostaglandins consists in their defense homeostatic function. PMID- 1862377 TI - [Antibacterial therapy of acute pancreatitis]. PMID- 1862376 TI - [Clinical and experimental studies of the effect of low-intensity laser irradiation on the blood and blood vessels]. PMID- 1862378 TI - [Principles of classification and care of patients with burns in mass accidents]. PMID- 1862379 TI - [Delta hepatitis]. PMID- 1862380 TI - [Characteristics of the course of myocardial infarction in middle-aged and elderly patients]. PMID- 1862382 TI - [Lipid peroxidation in patients with unstable stenocardia treated with adrenergic beta blockers]. PMID- 1862381 TI - [Activity of the sympathetic-adrenal system in myocardial infarction diabetes mellitus]. PMID- 1862384 TI - [Pneumonia in the acute period of cranio-cerebral injury]. PMID- 1862383 TI - [Corticoid secretion and patho-histological changes in the adrenal glands in hypertension]. AB - Hydrocortisone, 11-hydroxycorticosteroids and aldosterone were measured in 74 patients with a history of surgery on the sympathoadrenal system for stable essential hypertension. Morphologic structure of the sympathetic ganglia of the celiac plexus and adrenals removed during surgery was under study. The studies have revealed a relationship between pathohistologic changes in operation material and adrenocortical functional activity. The authors suggest a possibility of a relationship between morphofunctional changes in the adrenals and sympathetic ganglia, and enhanced nervous system efferent effects with the progress of the disease. PMID- 1862385 TI - [Use of a new calcium antagonist nifangin in chronic cor pulmonale]. PMID- 1862386 TI - [Significance of the degree of gastric acid secretion for evaluating the indications for surgical treatment of uncomplicated duodenal ulcer]. PMID- 1862387 TI - [Use of plasma-exchange plasmapheresis in the complex treatment of acute diffuse peritonitis]. PMID- 1862388 TI - [Lymphotropic therapy of acute peritonitis with antibiotics]. PMID- 1862389 TI - [Critical evaluation of the clinico-roentgenological symptoms of duodenal compression by the superior mesenteric artery]. PMID- 1862391 TI - [Immunocorrective treatment of amyotrophic lateral sclerosis]. PMID- 1862390 TI - [Diabeton in the treatment of stage I nephroangiopathy in insulin-dependent diabetes mellitus]. PMID- 1862392 TI - [Early prognosis of the outcome of stroke]. PMID- 1862393 TI - [Surgical treatment of acute inflammation of epithelial coccygeal passage]. PMID- 1862394 TI - [Present-day characteristics of etiology, epidemiology and clinical aspects of diphtheria in adults]. PMID- 1862395 TI - [Results of primary suturing of digital nerves of the palms]. PMID- 1862396 TI - [Neuropathies in cancer patients during chemotherapy with platinum preparations]. PMID- 1862397 TI - [Clinico-morphological characteristics of pericardial mesothelioma]. AB - The authors describe clinical and morphological features of a rare tumor, pericardial mesothelioma. Their findings lead them to a conclusion that the epithelioid cell form (tubular and papillary variants) is the most incident histologic form of this tumor. They emphasize that life-time diagnosis of pericardial mesothelioma is of paramount importance because rational chemotherapy permits prolongation of the patient's survival. PMID- 1862398 TI - [Early stages in the history of pulmonary oncology]. PMID- 1862399 TI - The effect of decompression on the natural course of spinal stenosis. A comparison of surgically treated and untreated patients. AB - The clinical course of 19 untreated patients with spinal stenosis (mean age, 60 years) was compared with that of 44 patients treated surgically (mean age, 65 years). The time of follow-up was 31 and 53 months, respectively. About 80% of the patients had neurogenic intermittent claudication. In the follow-up, one third of the treated and one half of the untreated patients still had neurogenic claudication. By visual analogue-scale estimation, 60% of those treated surgically and 33% of the untreated patients felt better. Fifty-eight percent of the untreated patients were unchanged. Neurophysiologic changes showed progression in almost all cases; it was more pronounced in the treated patients. No proof of severe deterioration was found in the untreated patients, and observation for 2-3 years seems to be a good alternative to surgery. PMID- 1862400 TI - Postoperative computed tomography three months after lumbar disc surgery. A prospective single-blind study. AB - In a prospective single-blind study, 60 patients surgically treated for lumbar disc herniation underwent clinical examination and computed tomography preoperatively and 3 months after surgery. At follow-up (58 patients; median, 31 months; range, 21-37 months), 29 patients had an excellent outcome (51%), 20 improved (33%), and 9 were unchanged or worse (16%). Dural or radicular scar tissue was present by computed tomography in 88% of the patients, but the findings could not be correlated with the clinical outcome. Recurrent or persistent disc herniation was found in 9% of the patients. The clinical outcome of patients with abnormal computed tomography did not differ significantly from patients without this finding. A relation between facet joint degeneration and less successful clinical outcome was demonstrated. Computed tomography (without contrast) 3 months after surgery gave little information which could be correlated with the clinical outcome. Patients with an excellent outcome had all degrees of intraspinal scar tissue. PMID- 1862401 TI - Disc degeneration in magnetic resonance imaging. A comparative biochemical, histologic, and radiologic study in cadaver spines. AB - Magnetic resonance imaging (MRI) findings of 89 autopsied intervertebral discs from 22 cadaveric lumbar spines were correlated with biochemical composition, conventional radiography, and histologic structure to study the nature of disc intensity changes seen in MRI. Discs with a low signal intensity on T2-weighted MRI were characterized by shortening of relaxation times, dehydration, and decreases in total proteoglycan content and chondroitin-keratan sulfate ratios in the nucleus pulposus. This corresponded well with previously published studies. In histologic structure, no obvious differences between MRI findings were found. In conclusion, a low signal intensity in a lumbar disc on T2-weighted MRI probably reflects a true biochemical disc degeneration, but its relation to structural degenerative changes is uncertain. Therefore, MRI seems to be a sensitive and a specific imaging modality for detecting pathologic biochemical disc changes in the spine of a young adult. PMID- 1862402 TI - In vivo and ex vivo magnetic resonance imaging evaluation of early disc degeneration with histopathologic correlation. AB - The in vivo and ex vivo microanatomic appearance of early disc degeneration were identified by magnetic resonance imaging and correlated with their respective histopathologic findings. Five cadaver spines (18 discs) and 25 patient studies (122 discs) all imaged at 1.5 Tesla were studied. Two signs of early degenerative disc disease were found: infolding and the central dot. Infolding of the central fibers of the outer annulus coalesced into a central dot of low signal intensity that was seen on both the ex vivo and in vivo images. Infolding was seen 29 of 122 times, and the central dot was observed 15 to 122 times on the in vivo images. A later form of degenerative disc disease was identified as a separation of the nucleus pulposus from the hyaline cartilage end-plate. This separation was seen as a linear area of either low or high signal intensity on the ex vivo images but only as a band of high signal intensity on the in vivo spin-echo 2,500 msec/80-msec images. Only 7 of 122 in vivo discs showed this separation. Internal herniation of nucleus pulposus into the outer annulus was seen only on the ex vivo images. Early degenerative disc disease may exist before there is loss of disc height or signal intensity on the long time-to-repetition (TR)/time-to-echo (TE) magnetic resonance images. PMID- 1862403 TI - Change of disc height, radial disc bulge, and intradiscal pressure from discectomy. An in vitro investigation on human lumbar discs. AB - Partial discectomy was done in vitro on 15 human lumbar discs from donors 20-40 years of age. The change of disc height, radial disc bulge, and intradiscal pressure was measured in relation to the mass of central disc tissue excised. Disc height decreases and radial disc bulge increases approximately in proportion with the mass of the tissue excised. At the same time, intradiscal pressure decreases. On average, removal of 1 g of disc tissue results in a height decrease of 0.8 mm and a radial bulge increase of 0.2 mm. Removal of 3 g of central disc tissue lowers the intradiscal pressure to approximately 40% of its initial value. A mechanical model is presented which explains the observed relation between the volume of material removed and the subsequent change of height, bulge, and pressure. The experimental results and the model provide insight into the rationale of disc pressurization. A high intradiscal pressure is a prerequisite for the mechanical function of the disc under physiologic conditions. PMID- 1862404 TI - Importance of bone mineral density in instrumented spine fusions. AB - The effect of equivalent mineral density on pedicular screw fixation strength was investigated. The equivalent mineral density of human vertebral bodies was correlated highly with the pullout force of Kluger screws (r2 = 0.61, P less than 0.02). A moderate to high correlation existed between density and vertical force (r2 = 0.42 for Kluger screws, r2 = 0.55 for Steffee screws, P less than 0.02). In calf vertebral bodies of higher density (146 +/- 14 mg/cc), the forces were significantly higher than in the human vertebral bodies (P less than 0.05). Human lumbosacral spines were instrumented with three different fixators: Steffee plates, AO fixateur interne, and Kluger fixateur interne. Of five specimens with a mean density of 88 +/- 11 mg/cc, one screw loosened. More than one screw loosened in six specimens with a mean density of 63 +/- 12 mg/cc, and no screw loosened in four specimens with a mean density of 114 +/- 38 mg/cc. Measurement of equivalent mineral density correlates with the fixation strength of the intrapedicular screws in vitro and should be considered in patients with signs of osteopenia before using pedicular screws for spinal fusions. It is also concluded that calf spines are a good model for testing implants because they tend to focus failure processes in the implant rather than in the implant-bone interface. PMID- 1862405 TI - Immunohistochemical demonstration of sensory nerve fibers and endings in lumbar intervertebral discs of the rat. AB - Although it is accepted that the intervertebral disc has a sensory component, it has not been previously shown by any specific method. Immunoreactivity of the physiologically active neuropeptide, calcitonin gene-related peptide (CGRP), was used as a specific marker of sensory nerve fibers and their endings in the intervertebral disc of the rat. In this study, positive fiber immunoreactivity was taken as an indication that those fibers were of sensory, and not sympathetic, origin. Immunoreactivity was found in the outer annulus fibrosus of all intervertebral discs studied. The CGRP-like immunoreactivity was also found in structures that resembled nerve endings. To the authors' knowledge, this is the first report presenting detailed positive evidence of sensory fibers and their endings in the lumbar intervertebral disc of any mammalian species. PMID- 1862407 TI - Radiologic interpretation of lumbar vertebral rotation. AB - The different parts of the lumbar pedicle were identified on an anteroposterior (AP) radiograph to determine reliable reference points to be used to quantify vertebral rotation. Standard AP radiographs were taken of dry lumbar vertebrae with 5 degrees increments in rotation in the transverse plane, ranging from 0 degrees to 30 degrees both to left and right. Identical sets of radiographs were taken with radiopaque markers around the middle and in the anterior and posterior parts of the pedicles. The anatomic center of the pedicle was found to lie slightly more lateral than the center of the pedicle halo. The inferior edge of the pedicle corresponded with the anterior part of the pedicle and the superior edge, with the posterior part. PMID- 1862406 TI - An analysis of normal back shape measured by ISIS scanning. AB - Two hundred seventy-one school children aged 10-16 years and 72 normal adults aged 21-59 years were scanned by ISIS. Subjects with any evidence of scoliosis were excluded from the study. Characteristic ISIS parameters of back shape showed no statistically significant differences related to age or sex for the children. Back shape in both men and women was not significantly different from that of the children, except for kyphosis angles which were greater. PMID- 1862408 TI - Concepts in mathematical modeling. PMID- 1862409 TI - Measurement of strength and endurance. The psychophysical lift test. PMID- 1862410 TI - Experimental spinal deformity produced by rib lengthening. PMID- 1862411 TI - Normal cervical spine morphometry and cervical spinal stenosis in asymptomatic professional football players. Plain film radiography, multiplanar computed tomography, and magnetic resonance imaging. AB - Diagnosis of cervical spinal stenosis or instability rests on the objective findings depicted on static and dynamic radiographs. Before abnormal spinal morphometry can be determined, it is first necessary to establish normal values for the specific patient population being evaluated. Several studies have attempted to establish norms for plain film measurements of the cervical spine in children and adults, but few have applied consistent methods for generating precise measurements. The first part of this study established normal values for cervical spinal morphometry and segmental spinal motion in the elite athlete. The second part of this study determined the most accurate screening method for detecting cervical spinal stenosis. Three sagittal diameters of the cervical spinal canal were compared to determine which represented the smallest midline diameter on static and dynamic radiographs. The Torg ratio was also evaluated as a method to detect significant cervical spinal stenosis and was shown to have a high sensitivity but poor positive predictive value. The study clarified why the ratio yields a large number of false positive cases. From the results of this study, an algorithm has been developed for the evaluation of stenosis of the cervical spine in athletes. PMID- 1862412 TI - Intervertebral disc injury complicating cervical spine trauma. AB - The incidence of acute herniated nucleus pulposus was determined in 55 patients with cervical spine trauma. A standardized protocol and a 1.5-T magnetic resonance image scanner was used to document a 42% incidence of acute herniated nucleus pulposus in patients studied within 72 hours of injury. The incidence of herniated nucleus pulposus was correlated with the patients' presenting neurologic status and mechanism of injury. The incidence of herniated nucleus pulposus was highest in patients with bilateral facet dislocations (80%) and anterior cord syndromes (100%). There was no statistically significant correlation between the incidence of herniated nucleus pulposus and patients' age or sex. PMID- 1862413 TI - The effect of spinal implant rigidity on vertebral bone density. A canine model. AB - An animal model of anterior and posterior column instability was developed to allow in vivo observation of bone remodeling and arthrodesis following spinal instrumentation. After an initial anterior and posterior destabilizing lesion was created at the L5-L6 vertebral levels in 63 adult beagles, various spinal reconstructive surgical procedures were performed--with or without bilateral posterolateral bone grafting, with or without bilateral oophorectomies, and with or without spinal instrumentation (Harrington distraction, Luque rectangular, Cotrel-Dubousset pedicular, or Steffee pedicular implants). Observation 6 months after surgery revealed a significantly improved probability of achieving a spinal fusion if spinal instrumentation had been used (X2 = 5.84, P = .016). Nondestructive mechanical testing after removal of all metal instrumentation in torsion, axial compression, and flexion revealed that the fusions performed in conjunction with spinal instrumentation were more rigid (P less than .05). Quantitative histomorphometry showed that the volumetric density of bone was significantly lower (ie, device-related osteoporosis occurred) for fused versus unfused spines. In addition, a linear correlation occurred between decreasing volumetric density of bone and increasing rigidity of the spinal implant (r = .778); ie, device-related osteoporosis occurred secondary to Harrington, Cotrel Dubousset, and Steffee pedicular instrumentation. Oophorectomized dogs became more osteoporotic than their surgically matched controls (posterolateral bone grafting alone, Cotrel-Dubousset pedicular instrumentation, and Steffee pedicular instrumentation); device-related osteoporosis added to the degree of hormonally induced osteoporosis (t = 5.0, P less than .0001). This is the first study to date documenting the occurrence of stress shielding in the spine secondary to spinal instrumentation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1862414 TI - Patients avoiding surgery. Pathology and one-year life status follow-up. AB - Patients were selected for a research study to determine the outcome of patients who had demonstrated enough pathology to have been viewed as surgical candidates and had chosen to avoid surgery. The purpose of the study was to identify the diagnostic categories and to obtain follow-up data on these patients. The patient population consisted of 66 patients with the following pathologies: disc disruption (one and two levels), disc disruption (three levels), stenosis, spondylolisthesis, instability, and herniated nucleus pulposus. The patients were followed for a period of 1 1/2 years and rated on the following lifestyle status categories: Returned to Work, Retired, Retraining, Able to Increase Activity Level, or No Change from Initial Status. Of the nonoperative patients, 18% returned to work. Twelve patients (18%) were retired. Eleven patients (16%) were placed in retraining programs. Twenty patients (29%) were able to increase activity level. Eleven patients (16%) fell under the category of no change. PMID- 1862415 TI - Clinical correlation between degenerative spine disease and dermatomal somatosensory-evoked potentials in humans. AB - The relationship between clinical status and preoperative and intraoperative dermatomal somatosensory-evoked potentials was investigated as a function of test site. Results indicated that the specificity and sensitivity of dermatomal somatosensory-evoked potentials varied with level of involvement: L5 demonstrated greatest agreement with equal correlation at L3, L4, and S1. Variables that influenced correlation included history of previous surgeries, type of anesthetic used, interpretation criteria, and whether the patient was awake or asleep. It was concluded that dermatomal somatosensory-evoked potentials can provide the surgeon with diagnostic and intraoperative information regarding the functional integrity of single nerve root function. PMID- 1862417 TI - The importance of posterior epidural fat pad in lumbar central canal stenosis. AB - Ninety-three patients with lumbar central canal stenosis were prospectively evaluated to determine whether the posterior epidural fat was an important component in the pathogenesis of thecal sac compression. Results of this study indicated that, in patients with acquired stenosis secondary to facet arthrosis, posterior compression of the thecal sac by epidural fat was identified. This finding was not observed in patients with stenosis secondary to anterior column pathology or in patients with developmentally large facets. PMID- 1862416 TI - Lamina repair and replacement to control laminectomy membrane formation in dogs. AB - This study examined the efficacy of lamina repair by the use of various techniques to prevent postlaminectomy scar formation in a canine system. Five level noncontiguous laminectomies were performed on six adult canines. The most caudal (Site 1) was left uncovered and served as the control. Exposed dura at each of the remaining four levels was covered with one of the following: Site 2, free autogenous laminar bone graft; Site 3, polymethylmethacrylate; Site 4, Teflon-Proplast composite; Site 5, collagen gel. The dogs used in the study were killed 16 weeks after surgery. Three specimens were examined by plain roentgenography and computerized tomography, two specimens were examined histologically, and the remaining four specimens were graded according to scar volume and scar adherence, as detected during gross dissection of the postlaminectomy scar. No repair technique interfered with roentgenography evaluation. The least scar and fewest adhesions were present under the free bone graft repair site. The Teflon-Proplast composite and polymethylmethacrylate both limited the amount and adherence of scar. Collagen gel and control sites were indistinguishable in this study. It is concluded that lamina repair with a solid material covering exposed dura significantly reduces the formation of postlaminectomy membrane and scar. PMID- 1862418 TI - Lumbar facet fracture as a possible source of pain after lumbar laminectomy. AB - This study compared 50 patients with lumbar facet fractures and continued pain after lumbar laminectomy with a postlaminectomy control group without facet fractures. Computed tomographic analysis compared variables including direct measurements of bone resection. Average follow-up between surgery and postsurgical computed tomographic examination was 3.2 years. In the fracture group, more than one half of the bone immediately above the flare of the inferior articular process at the level of the laminectomy, measured in a medial to lateral direction, had been resected. No one in the control group had more than one quarter of this bone removed (P = .0001). Lumbar facet fractures may be one cause of late postlaminectomy pain. Caution in resection of a particular area of bone may avoid this problem. PMID- 1862419 TI - Rotation of load during the prelift period. AB - Lifting is a major source of back injuries because of the mechanical effects on the spinal structures. A number of methods are known by which a lifter can reduce the load on the spine during lifting. This study explores an additional method: rotation of the load before it is actually lifted off the ground. The hypothesis tested is that when a lifter lifts a box, he or she rotates it before it leaves the floor. By the use of an optoelectronic system to study weight box rotation, it was established that rotation occurs in every lift before the actual lift occurs. Rotation time increased with increasing load, indicating that the rotation technique is more important when load reduction is most critical. PMID- 1862420 TI - Development of a prosthetic intervertebral disc. AB - This article is a preliminary report of a 10-year investigation of the development of an intervertebral disc prosthesis. Spinal fusion is a method for the treatment of chronic, disabling low-back pain that does not respond to nonoperative treatments. Spinal fusion, however, has various adverse effects, and the results of spinal fusion are often unpredictable. The goal of this research project was to develop disc prostheses that have mechanical properties very similar to those of natural, normal discs. Two types of disc prosthesis, one with fiber-reinforced polyurethane and the other with multicomponent, non-fiber reinforced polymers (C-Flex), have been designed and manufactured. The fiber reinforced disc was made of polyurethane end-plates with A100 hardness, a homogenous nucleus with A40, and 12 layers of multidirectional (0, +45 degrees), fiber-reinforced anulus with A40 polyurethane. The design and modeling of the multicomponent polymers (non-fiber-reinforced) was made of C-Flex endplates with A90 hardness, a nucleus with A35 occupying 35% of the volume, and an anulus with 70A. Mechanical testing of these disc prostheses demonstrated similar mechanical properties to those of natural, normal discs. PMID- 1862421 TI - Design of an intervertebral disc prosthesis. AB - This article presents criteria for the design of a lumbar intervertebral disc prosthesis that take into consideration issues of endurance, materials behavior, geometry, kinetics, motion constraints, fixation to bone, and safety. The criteria and design philosophies discussed are generally applicable in the synthesis of any new implant system. Specifications of the design of a disc prosthesis are presented along with an evaluation of the design based on some of the preliminary test data. PMID- 1862422 TI - Correlation of radiologic assessment of lumbar spine fusions with surgical exploration. AB - Although inspection of posterolateral lumbar fusion is the best method of determining its solidity, routine exploration of the fusion is somewhat impractical because of the morbidity and expense involved. Removal of internal fixation devices or implantable batteries or reoperation for failed back surgery enabled the exploration and assessment of lumbar spine fusions in 214 operations on 175 patients. The preoperative radiologic assessment (plain roentgenographs, polytomography, bending films, and computed tomographic scans) were correlated with surgical findings. This study indicated a significant percentage of inaccuracy of all radiologic modalities used. Noncorrelations were present in 36% of plain roentgenographs, 41% of polytomograms, 38% of bending films, and 43% of computed tomographic scans. Radiologic inaccuracy was manifest on both the positive and negative sides. Computed tomographic scanning presented the lowest percentage of inaccuracy (22%) and bending films the highest percentage (27%). Based on these findings, there exists the need for more accurate noninvasive methods to determine the solidity of spine fusions. PMID- 1862423 TI - Translaminar facet joint screw fixation for lumbar and lumbosacral fusion. A clinical and biomechanical study. AB - Various systems of supplementing bone grafts with internal fixation in the lumbosacral spine have been used in an effort to improve fusion rates. This study reports biomechanical data of cyclic loading cadaveric spines instrumented with translaminar facet screws as well as early clinical results on this technique. Static loading tests comparing uninstrumented and instrumented spinal motion units show that a ninefold increase in flexion load is necessary for constant displacement after facet screw fixation. Repetitive loading tests show only a small decrease in stiffness of instrumented segments even after 5,000 cycles. To date, 35 patients have undergone fusion by this technique as performed by one surgeon. After excluding Workers' Compensation cases and cases with less than 2 years follow-up, there were 18 cases available for review. Twelve of these 18 cases were two-level fusions. Ten patients underwent concomitant discectomy or nerve root decompression. There were no cases of iatrogenic neurologic injury or pseudoarthrosis. It is concluded that translaminar facet screws have a sound biomechanical basis and are a valuable addition to lumbar fusion procedures. PMID- 1862424 TI - Triangulation of pedicular instrumentation. A biomechanical analysis. AB - Tensile load-to-failure pullout tests were performed on 54 cadaveric spinal segments. The vertebrae were grouped by adjacent levels and matched for bone mineral density (g/cm2), which was measured by dual-photon absorptiometry. Triangulation of Steffee screws and CD pedicle screws was accomplished by transverse plates specifically designed to increase fixation within the same vertebra before the longitudinal Steffee plate or CD rod was applied. A transverse plate with adjustable length was also tested to accommodate variable interpedicular distances. Comparative pullout load-to-failures were as follows: laminar hook, 809 SE 99.4 N; single CD pedicular screws, 863 SE 108 N; single Steffee pedicular screw, 1245 SE 75.3 N; adjustable transverse plate, 1341 SE 114; triangulated Steffee pedicle screws with a transverse plate, 1701 SE 151 N; and triangulated CD pedicle screws with a transverse plate, 2096 SE 115 N. Three triangulated constructs with pedicle screws and a transverse plate (CD, Steffee, and Kirschner) provided significantly greater fixation than conventional pedicular or laminar hook based instrumentation systems (P less than 0.05). Improved treatment of spinal deformities in the elderly and osteoporotic population is dependent on improving the fixation at the metal-bone interface of spinal implants Particularly in osteoporotic vertebrae, the strength of fixation of two triangulated pedicle screws is better than either laminar hooks or single pedicle screws. The strength of fixation of triangulated pedicle screws connected by a transverse plate is superior to a single pedicle screw because it is dependent on the mass of bone between the screws rather than simply the amount of bone within the screw thread.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1862425 TI - A carbon fiber implant to aid interbody lumbar fusion. Mechanical testing. AB - A carbon-fiber-reinforced polymer implant has been designed to aid interbody lumbar fusion. The cage-like implant has ridges or teeth to resist pullout or retropulsion, struts to support weight bearing, and a hollow center for packing of autologous bone graft. Because carbon is radiolucent, bony healing can be imaged by standard radiographic techniques. The device has been mechanically tested in cadaver spines and compared with posterior lumbar interbody fusion performed with donor bone. The carbon device required a pullout force of 353 N compared with 126 N for donor bone. In compression testing, posterior lumbar interbody fusion performed with the carbon device bore a load of 5,288 N before failure of the vertebral bone. Posterior lumbar interbody fusion performed with donor bone failed at 4,628 N, and unmodified motion segments failed at 6,043 N. The carbon fiber implant separates the mechanical and biologic functions of posterior lumbar interbody fusion. PMID- 1862426 TI - Surgical anatomy of the sacrum. A guide for rational screw fixation. AB - Anterior sacral anatomy was studied to allow safe sacral screw placement. The study included 27 bony sacra. Intrapelvic dissections were performed. Cadaveric specimens were dissected and photographed. The position and angulation of the first sacral foramen was extremely variable. After the position of the L5 root, sacral roots, and iliac vessels, was considered, safe posterior sacral screw implantation could be assured through placement above the level of the first sacral foramen directed medially toward the promontory, parallel to the superior sacral end-plate. Complications of indiscriminate screw placement included L5 root damage, iliac vein penetration, and intractable perineal pain due to sacral root injury. Preoperative computed tomography with the scanner gantry tilted to parallel the superior sacral end-plate defined the great vessels, neural foramens, inclination of the superior sacral end-plate, and prominence of the posterior ileum. Surgical accuracy was evaluated after surgery with computed tomography. PMID- 1862427 TI - Anatomic consideration for sacral screw placement. AB - Instrumentation of the lumbosacral spine increasingly involves screw fixation to the sacrum. Recommended locations and techniques for screw placement vary, particularly when bicortical purchase of the sacrum is performed. The purpose of this study was to describe the critical anatomy and potential injuries to neurovascular and visceral structures anterior to the sacrum. Lack of awareness can lead to life-threatening complications. The study included 22 fresh human cadavers with no prior spinal surgery. Specimens were placed in a prone position, and the lumbosacral spine was exposed. Two 6.5-mm screws were inserted using one of two techniques, respectively: Starting just inferior to the S1 facet one screw was angled 25 degrees caudally and 30 degrees laterally; in the second technique, lateral inclination was increased to 45 degrees. In addition, all specimens had screws placed in the S2 pedicles. An anterior dissection was performed to allow evaluation of the neurovascular and visceral structures at risk for injury by, or adjacent to, the screw tips. All significant neurovascular structures in the area of concern were constant in position. The internal iliac vein and the lumbosacral nerve trunk were most at risk for injury by the 30 and 45 degrees laterally directed screws. The sigmoid colon, though close to the S2 screw, was protected by its mesentery. Screws placed in the S1 pedicle were least likely to injure the neurovascular bundle. A lateral and a midline safe zone were identified. PMID- 1862428 TI - Unilateral lumbar fusion. AB - Unilateral fusion of the lumbar spine is rarely necessary or indicated. However, in patients with a "far-out syndrome" requiring decompression or in cases where unilateral posterior element resection is necessary for any reason, it may be both necessary and indicated. This unilateral destabilization effectively removes one leg of the tripod, rendering that intervertebral joint potentially unstable. The charts and radiographs of 13 patients (seven men, six women) with an average age of 60 years (range, 25 to 76) who underwent unilateral fusion were retrospectively reviewed. Follow-up time ranged from 12 1/2 to 2 years with a median follow-up of 8 years. Eleven of the fusions were at one level, and two were at two levels. Seven patients had a far-out syndrome secondary to degenerative scoliosis; four were secondary to spondylolisthesis. Two patients had an osteoid osteoma involving a pedicle. A paraspinal approach was used in the majority of patients. Autologous bone graft was used in all patients. Unilateral pedicle screw fixation was used in the last patient in the series. The fusion rate was 85% (11/13). Three patients were smokers, two of whom developed pseudarthrosis. Disc space height did not appear to affect fusion rate. There was no progression of slip noted in any of the patients. One complication was noted in this group: a moderate postoperative infection, which cleared spontaneously. PMID- 1862429 TI - Two-point fixation of the lumbar spine. Differential stability in rotation. AB - Single vertebral motion segments were tested in torsion. The adjacent vertebrae were transfixed by two 3-mm Steinman pins placed vertically. These were applied in five different positions: between the anterior vertebral bodies, posterior vertebral bodies, pedicles, transverse processes, and lamina. Rotational displacement was limited the most by transfixation between the vertebral bodies (position one or two). Disrupting the anulus fibrosus significantly increased rotation in all positions except those in the vertebral body. These findings may imply that spinal fixation devices that engage the vertebral bodies may offer inherent advantages over purely posterior devices in stabilizing a vertebral motion segment. In addition, an interbody arthrodesis may prevent intervertebral motion better than a posterior or posterolateral fusion. PMID- 1862430 TI - Reduction of high-grade slips (grades III-V) with VSP instrumentation. Report of a series of 41 cases. AB - Records of 41 patients were reviewed for early complications resulting from reduction of high-grade spondylolisthesis. Blood loss averaged 1,427 ml. There were no cases of infection, dural tears, or bladder or bowel dysfunction. Two cases of transient foot drop and one case of permanent foot drop developed. A lumbar plexus stretch palsy occurred in one patient. Long-term results were evaluated in 20 patients followed up 2 or more years after surgery. Three of the 20 did not have interbody fusions and lost their reductions. All 20 patients went on to fuse with no pseudoarthrosis. One case of broken plate and two cases of broken screws occurred. Patient satisfaction ranged from good to excellent. Results suggest that reduction of high-grade slips with interbody fusion is a safe and effective procedure. PMID- 1862431 TI - Deficiency of the seventh component of complement. A case report. AB - Deficiency of the 7th component of the complement cascade was diagnosed in a white male with recurrent meningococcal infections. This deficiency has not previously been reported in South Africa. PMID- 1862432 TI - Urinary epidermal growth factor in males with and without renal calculi. PMID- 1862433 TI - Local and regional anaesthetic techniques. PMID- 1862434 TI - The possible significance of fissured tongue in tuberculosis patients. PMID- 1862435 TI - How genes cause inherited large-bowel cancer. PMID- 1862436 TI - Rett syndrome. PMID- 1862437 TI - [The ethics of resource allocation]. PMID- 1862438 TI - Injuries of the cervical spinal cord. The Ga-Rankuwa Hospital experience. AB - A retrospective analysis of 40 cervical spinal cord-injured patients showed that the commonest cause of injury was a motor vehicle accident (60%). C5 - 6 was the level most commonly injured. Eight patients had complete and 32 incomplete neurological lesions. Surgery was the elective treatment in 78%. Surgical treatment did not result in more rapid mobilisation out of bed nor did it significantly reduce the period of hospitalisation, compared with non-surgical management. No patient deteriorated neurologically, 5 remained unchanged and 35 improved. Twenty-one patients eventually walked. PMID- 1862439 TI - Acute respiratory infections as an important cause of childhood deaths in South Africa. AB - Compared with other major preventable childhood diseases, such as diarrhoea, acute respiratory infections (ARI) have received comparatively little attention as an important cause of death in children. In this study of mortality from ARI in South Africa, national data was examined for the period 1968-1985, and data for Greater Cape Town for 1987. Almost 90% of ARI deaths were attributable to pneumonia and large inter-group differences were found that favoured whites and Asians over blacks and coloureds. For example, during 1980-1985 the mortality rate for pneumonia in coloured infants under 1 year of age was 11 times that observed in whites (88 v. 981/100,000). Pneumonia accounted for 14.5% of coloured and 12.7% of black deaths under 1 year of age during this period, compared with 6.7% of white and Asian deaths. The mortality rates from pneumonia declined substantially (50%) over the 18-year period in whites, coloureds and Asians. Sequential data for blacks is not available. There was a marked seasonality of deaths among coloured and Asian infants, with rates peaking in winter months. In Cape Town, pneumonia is now a more important cause of death among white and coloured children than diarrhoea, while it ranks with diarrhoea as a cause of death in black children. In all population groups, death rates from ARI are from 7 times to 270 times greater than those recorded in Western European countries. Studies are urgently required to discover why South African children suffer such a high mortality from ARI and how these deaths can be prevented. PMID- 1862440 TI - Preventing cystic fibrosis in the RSA. AB - Prenatal diagnostic testing for cystic fibrosis (CF) in South Africa has been available by microvillar enzyme (MVE) assay since 1984 and by DNA investigation since 1987. The advantages and practical uses of these two procedures are reviewed. Over the period 1984-1989, 59 MVE assays and 13 DNA investigations (1 woman had both done; total number of pregnancies tested 71) were performed for the prenatal diagnosis of CF in high-risk families. Of the 71 pregnancies tested (65 white woman, 4 mixed race and 2 Indian), 18 fetuses were found to be affected: of these, 15 couples chose to have the pregnancies terminated. In 2 fetuses tested the MVE assays were 'equivocal' and the babies were born affected. By using population genetic and demographic data it is estimated that the present rate of prenatal diagnosis and prevention satisfies about one-quarter of the projected and practically achievable annual need. It is also tentatively shown that only about 60% of the projected number of high-risk families are at present on record. It is concluded that more systematic efforts should be directed at carefully guided information and awareness campaigns, in order to draw more CF families into the mainstream of voluntary genetic services. The identification and cloning of the CF gene (in 1989) has made it possible to extend considerably the present strategy of prevention and to include lower-risk and extended CF families in due time. PMID- 1862442 TI - Reversal of structural changes in hypertensive--a major prospect for the future? PMID- 1862441 TI - The genetic basis of cancer. AB - Cancer is essentially a genetic disease resulting from congenital or acquired alterations in some cells of the patient. Such changes may occur in particular oncogenes and are responsible for the tumour phenotype of the affected population of cells. Oncogenes function by continuous positive action in the mitogenic pathway, and may become activated by point mutations, chromosomal rearrangements, gene amplification or viral insertion events. In contrast, unaltered tumour suppressor genes are responsible for suppressing the neoplastic phenotype, and their inactivation by deletion or mutation permits cancerous development in the affected cells. The genetic model of carcinogenesis is thus based on the idea that mutations at the DNA level create a functional imbalance between the oncogenes and the tumour-suppressor genes, resulting in uncontrolled clonal proliferation. It is likely that the clinical importance of these recent findings will soon be realised and utilised in the development of therapies and diagnostic procedures that will directly benefit the patient. PMID- 1862443 TI - Is the ESR dead? PMID- 1862444 TI - Psychiatry for a new South Africa. PMID- 1862446 TI - Impact of the political violence in Natal on emergency surgical services of a tertiary hospital. AB - In order to investigate the impact of the political violence in Natal on a tertiary hospital's emergency surgical services, 5 days in February 1990 (based on newspaper reports of political violence) were identified and matched for the day of week and time of month to obtain comparable control days in February 1989. Data for each of the 10 days were obtained from casualty department attendance registers and a 40% random sample of emergency outpatients' charts. Comparing violence to control days, the total number of patients treated in casualty increased by 9.6% (1,915 v. 1,747), first visits to casualty by black patients increased by 34.4% (1,741 v. 1,295) and emergency patients treated in the casualty department increased by 29.6% (206 v. 159). Gunshot injuries accounted for 21.4% and 3.1% of surgical emergencies on violence and control days, respectively (relative risk 6.79; 95% confidence interval 2.76-16,73; P less than 0.001). Men comprised 76.2% and 65.4% of surgical emergencies on violence and control days, respectively (P less than 0.05). The mean age of surgical emergency patients with gunshot injuries was 26.4 years on violence days and 31.4 years on control days. Among surgical emergencies, gunshot injuries accounted for 19.2% of ward admissions on violence days compared with 5% on control days. Political violence in Natal increased the utilisation of tertiary hospital emergency surgical services, particularly for young black men with gunshot injuries requiring inpatient care. Until there is peace in this region, tertiary hospital emergency surgical services need to be strengthened and prepared to cope with the trauma resulting from the political violence. PMID- 1862445 TI - A retrospective study of spinal cord injuries in Cape Province rugby players, 1963-1989. Incidence, mechanisms and prevention. AB - A retrospective study was undertaken to determine aetiological factors for 117 catastrophic neck injuries in rugby players admitted to the Spinal Cord Unit, Conradie Hospital, Cape Town, between 1963 and 1989. Nineteen of these players were known to be dead; the files of another 10 were missing. Questionnaires were sent to the remaining 88 players and 52 responded (59%). Their data were supplemented with information obtained from the medical records of the patients who did not respond. The annual number of admissions increased dramatically after 1976 with 83% of all injuries occurring after that date. A further increase since 1984 contrasts with a falling incidence of these injuries in Britain, Australia and New Zealand. Increased risk of injury was related to the following factors: 98% of injuries occurred in matches and 81% were incurred by adults; 69% of injuries occurred in age-group A team or senior first team players; and 57% of injuries occurred in the tackle situation and 39% in scrums, rucks and mauls. Hooker, centre and flyhalf were the playing positions at greatest risk. Injuries were more common in early season matches and again after the mid-season break. This study confirmed that spinal cord injuries occur under predictable circumstances and are therefore foreseeable and preventable. The high incidence of these injuries in the Cape Province is as unacceptable today as it was when first reported in 1977. PMID- 1862447 TI - A methodology for resource allocation in health care for South Africa. Part IV. Application of South African Health Resource Allocation formula. AB - The primary concern of this concluding article in a series is the application of the South African Health Resource Allocation (SAHRA) formula proposed in the previous article (SAMJ 1990; 77: 456-459). Target allocations based on this formula are compared with current budgets to estimate the extent of geographical maldistribution of health care resources. Under the present health service structure, the direction of redistribution of these resources should be from the provinces to 'homelands'. A number of refinements to the crude formula, such as the introduction of a more rational regionalisation policy and accounting for the teaching commitments of academic hospitals, are considered and their effects illustrated. Despite data deficiencies and the wide range of possible technical modifications to SAHRA, the concept of basing resource allocation decisions on an internationally applied formula is worthy of public debate. PMID- 1862448 TI - Support systems, facilities and staffing of clinics in Mhala, Gazankulu--are they adequate? AB - A study comprising in-depth interviews of sisters in all 15 rural clinics in the Mhala district of Gazankulu showed them to experience major problems with support systems: radiophone communication was unreliable (and even absent in 3 clinics); transport was inadequate; the cold chain was not well maintained and essential drugs and equipment were absent (only 1 clinic had all the equipment to manage a neonatal resuscitation adequately). There were also serious deficiencies in facilities, lack of running water and electricity posing the most serious problems (resulting in deliveries and suturing of episiotomies by candlelight). Other pressing problems include inadequate waiting space and patient privacy. Staffing at the clinics fell well below what is required, yet the commitment of staff was often inspiring. The state of the clinics must be seen within the constraints of 'homeland' policy and the unequal distribution of the country's health care resources. Despite these limitations the clinic service can be improved. Recommendations are made for this, concentrating on improving support structures rather than on the more costly improvement of facilities. PMID- 1862449 TI - Sex and the brain. AB - Differences between the sexes in perception and cognition have been extensively documented and widely accepted as applicable to the majority of humans. Understanding of their aetiology can only be achieved by investigation of both hormonal and social factors. A significant recent advance, supporting the role of hormones, is presented. This study correlated corpus callosum size, sex and handedness. It showed that all females have a significantly larger isthmus (part of the corpus callosum) than consistently right-handed males. The inference is that women tend to use both hemispheres and most males only one. This has important educational and work-deployment implications. PMID- 1862450 TI - von Willebrand's disease in Zimbabwe. A report on 3 families. AB - Three families with clinically typical features of von Willebrand's disease are described. One family had features to suggest type II disease. Von Willebrand's disease appears to be rare in Africa, but this may be due both to lack of awareness among clinicians and insufficient laboratory facilities. PMID- 1862451 TI - William Jolly--father of medical science in South Africa. AB - William Jolly graduated in medicine at Edinburgh University in 1906 and became research assistant to Sir Edward Sharpey Schafer. He also mastered various techniques in electrophysiology under Einthoven, graduating D.Sc. in 1911. In 1911 he was appointed first Professor of Physiology and in 1918 first Dean of the Faculty of Medicine at the University of Cape Town. He conducted and stimulated research there and in recognition thereof was awarded an Honorary LI.D. by Edinburgh University and a special allowance from the University of Cape Town. He was President of the Royal Society of South Africa, a trustee of the South African Museum and a member of the National Research Council and Board. PMID- 1862452 TI - A milestone in cardiac transplantation. PMID- 1862453 TI - Awareness of AIDS among black mineworkers. PMID- 1862454 TI - Invasive blood pressure measurement. PMID- 1862455 TI - Thyroid lymphoma and its management. PMID- 1862456 TI - Schistosomiasis of the female genital tract. PMID- 1862457 TI - Failure of recommended maternal therapy to prevent congenital syphilis. AB - A pregnant women with secondary syphilis received appropriate therapy with penicillin in the last trimester of pregnancy. At delivery, her titre had fallen fourfold, and the baby had a non-reactive cord blood titre at birth. However, the treatment failed to prevent infection in the infant, and the baby had developed signs of congenital syphilis at 10 weeks of age. The definition of "adequate therapy" of pregnant women is unclear, and recent guidelines are contradictory. Therefore, literature that pertains to penicillin therapy in pregnancy is reviewed, and new guidelines for therapy proposed. PMID- 1862458 TI - Partner notification and the control of human immunodeficiency virus infection. Two years of experience in San Francisco. AB - To evaluate partner notification of opposite-sex sexual partners of AIDS patients as a means of limiting sexual and vertical transmission of human immunodeficiency virus (HIV), the authors examined the first 27 months of their experience with partner notification. Overall, of 145 AIDS patients eligible to participate, 51 (35%) were interviewed and identified 135 opposite-sex sexual partners. Of the 135 partners, 59 (44%) were interviewed and 34 (25%) were tested, resulting in the diagnosis of 7 (5%) HIV-infected partners. Refusal rates for index patients and partners were low (9% and 12%, respectively). Costs for the program were $454 per partner interviewed and $2,203 per seropositive partners identified. The authors conclude that although partner notification is more expensive than more widely targeted AIDS prevention and education efforts, its ability to target case finding, education, and counseling to women at highest risk of infection makes it potentially cost-effective for prevention of vertically transmitted HIV infection. PMID- 1862459 TI - Test method for evaluating the permeability of intact prophylactics to viral-size microspheres under simulated physiologic conditions. AB - The alarming number of AIDS cases has increased the attention given to barrier devices such as condoms. The authors describe a new test method that evaluates the permeability of the intact condom when subjected to simulated physiologic conditions. Fluorescent-labelled polystyrene microspheres (110 nm diameter) are used to model cell-free virus. Physical and chemical conditions that are present during coitus, such as pressure, pH, and temperature, are considered in the design of the method. The testing chamber is designed to be continuously monitored for changes in fluorescence due to leakage across the condom surface. The sensitivity of the system is 1 x 10(-5) of the original concentration of microsphere solution (3.4 x 10(11) particles/mL), which corresponds to leak rates as small as .001 microL/sec. The test provides an in vitro test of barrier material permeability relevant to actual use. PMID- 1862460 TI - Comparison of cefotetan plus doxycycline with cefoxitin plus doxycycline in the inpatient treatment of acute salpingitis. AB - Pelvic inflammatory disease (PID), one of the major sequelae of the current epidemic of sexually transmitted diseases, has been shown to be a polymicrobial infection. This study compares the efficacy and safety of two broad-spectrum combination drug regimens, cefotetan with doxycycline and cefoxitin with doxycycline, in the treatment of PID. A total of 108 patients with acute salpingitis were hospitalized and randomized into two treatment groups: cefotetan/doxycycline (N = 54) and cefoxitin/doxycycline (N = 54). Before antibiotic administration, Chlamydia trachomatis was identified in 17 (16%) of the patients, Neisseria gonorrhoeae from 72 (67%), and anaerobic and aerobic bacteria were identified from the endometrial cultures of 86 (80%). There were seven tubo-ovarian abscesses (TOAs) that were diagnosed in the cefotetan group, and six in the cefoxitin group. Clinical cure was achieved in 51 of 54 (94%) patients in each group. Of the six patients whose treatment failed, all had positive cultures for N. gonorrhoeae and facultative/anaerobic bacteria, whereas none had C. trachomatis. Two patients from each study arm whose treatment failed were diagnosed with TOAs and responded subsequently to clindamycin plus an aminoglycoside. Cultures that were obtained after the completion of inpatient treatment showed the eradication of C. trachomatis and N. gonorrhoeae in all patients. Also, both regimens were effective in reducing aerobic and anaerobic pathogens. Finally, both regimens were well tolerated, with few side-effects. PMID- 1862462 TI - The concept of core and its relevance to the epidemiology and control of sexually transmitted diseases. PMID- 1862461 TI - A population-based serosurveillance of syphilis in Costa Rica. AB - As part of a case-control study to investigate the high incidence of cervical cancer in Costa Rican women, the seroprevalence of the treponematoses, in particular, syphilis was determined. In each age group, women with a history of two or more sex partners were two to four times more likely to be seroreactive in tests for syphilis than women with zero or one sex partner. The highest percentage of reactive results in the microhemagglutination assay for antibodies to Treponema pallidum (MHA-TP) was seen in samples from women aged 50-59 who had had two or more lifetime partners (23.8%). Three observations from our study support reactivity due to syphilis rather than yaws or pinta: (1) a similar percent of reactive rapid plasma reagin (RPR) card test results among MHA-TP reactors in the two age groups of women who were surveyed (42 vs. 49%) was observed; (2) women who were seroreactive in the MHA-TP had multiple risk factors for STD [low socioeconomic status (9.4%), urban residence (22.8%), first intercourse under 16 years of age (14.1%), and multiple sex partners (26.3%)], and (3) only sexually experienced women had reactive results in the MHA-TP test. PMID- 1862463 TI - Is the concept, "agents of sexually transmitted disease" still valid? PMID- 1862465 TI - Noeggerath and "latent gonorrhea". PMID- 1862464 TI - Hepatitis B infection among Chinese STD patients in Kuala Lumpur, Malaysia. AB - This study documents the prevalence of Hepatitis B serological markers among STD patients who have had multiple sexual partners in Kuala Lumpur, Malaysia, and compares the rates with those of a sample of the population with single or no sexual partners. A total of 336 Chinese STD patients (multiple partners group) and 234 Chinese control subjects (non-multiple partner group) were screened. Those with a history of blood transfusion or parenteral drug abuse had been excluded from the study, and all study subjects were heterosexuals. The overall carrier rate was 9.2% for the multiple partner group (MP group) and 6.8% for the non-multiple partner group (NMP group). Infection rates were 64.3% for the MP group and 38.9% for the NMP group. After adjustments for age and sex, there was no significant difference in carrier rates between the two groups, but infection rates were significantly different with the MP group, being 3.2 times more likely to acquire infection than the NMP group. The study concludes that in heterosexuals, those with multiple sexual partners have increased chances of acquiring HBV infection. PMID- 1862466 TI - Crack, sex, and STD. AB - Increasing rates of syphilis, gonorrhea, chancroid, and sexually transmitted human immunodeficiency virus infection appear to be related to crack cocaine use. This article critically reviews 16 epidemiologic studies that examine drug use, sexual behavior, and sexually transmitted disease (STD). Eight studies found an association between crack and STD, one study found no association between crack and STD, and seven studies found STD to be related to other drugs or methods of cocaine use. The exchange of sex for money or drugs was associated with STD in seven studies. Publications that were reviewed have numerous methodologic weaknesses: broader sampling, uninfected comparison groups, and greater specification of drug use and sexual risk behaviors are needed. Further research should compare different drugs and associated sexual behavior and STD to assess the unique risk conferred by crack. Designing effective interventions will require investigation of risk behavior determinants and barriers to health care. PMID- 1862467 TI - Alternatives to Swan-Ganz cardiac output monitoring. AB - When we are concerned about the adequacy of peripheral oxygen delivery, our monitoring efforts focus on cardiac output as the component easiest to manipulate. Thermodilution is the current method of determining cardiac output because of logistic convenience, but by no means should it be considered the gold standard. Thoracic electrical bioimpedance is an appealing alternative because of its simplicity, noninvasiveness, and ability to track physiologic trends, but there have been a number of warnings against relying on it exclusively, at least until it is further developed. Doppler ultrasound appears to be a valid method in skilled hands, but its accuracy in quantitating cardiac output, especially in the critically ill, remains questionable. Mixed venous oximetry and transcutaneous oxygen monitoring are promising but are still being evaluated. PMID- 1862468 TI - Placement and complications of monitoring catheters. AB - Vascular access is a necessary evil in critically ill patients, a population that is at high risk for complications. Appropriate planning and attention to detail minimize the associated risks while maximizing the benefits derived from catheter use. PMID- 1862469 TI - Sepsis. What it is and how to recognize it. AB - Sepsis, shock, and resuscitation may result in various degrees of ischemia perfusion injury that may produce widespread organ dysfunction through complex interactions and activation of host immunoinflammatory processes. As the pathophysiologic mechanisms of the inflammatory response are better defined, we may be able to modulate the generalized inflammatory state we know as sepsis and prevent the development of multiple organ failure syndrome. At present, however, the mainstay of therapy remains prompt resuscitation to eliminate regions of hypoperfusion and to limit as much as possible those factors that predispose to further organ injury while the source of inflammatory stimulation is being identified and controlled. PMID- 1862470 TI - Antibiotic choices in surgical intensive care unit patients. AB - Antibiotics have dramatically changed the care of the critically ill patient over the last 60 years. Patients with complex physiological conditions present with infectious processes requiring the effective use of antimicrobial drugs. In many situations, the inability to eradicate the infectious process is complicated by the progressive development of resistance among the causative organisms. Systemic antibiotic prophylaxis is warranted only for the prevention of wound infections. Regimens in these cases should use large doses of nontoxic antibiotics covering the spectrum of organisms likely to contaminate the wound. The duration of wound prophylaxis should be short, essentially covering only the period of active wound closure; this is usually less than 24 hours. Prevention of most other infections in the ICU depends on the recognition and correction of the various disturbances of host defenses. Topical antibiotic therapy may reduce the level of colonization for a few specific types of infection. Initial empiric antibiotic therapy should be started for clear indications. The antibiotics chosen should be those most likely to be effective against the probable organisms, those which have the lowest toxicity, and those with the smallest likelihood of inducing multiresistance. They must be adjusted promptly based on the microbiologic sensitivities observed. The realization that the physiology of critical illness may alter the normal relations between drug dosages and the tissue antibiotic levels obtained mandates a different approach to the treatment of these patients. The drug volumes of distribution are generally markedly expanded in these patients. Furthermore, these patients require high tissue antibiotic concentrations to improve the chances for successful therapy. Thus, the antibiotics selected must be capable of providing these levels without significant toxicity to the host. Therapy should be continued based on the clinical response observed. Premature cessation of effective therapy often results in relapse. PMID- 1862471 TI - Deep venous thrombosis in the surgical intensive care unit. AB - The ICU patient population is at a high risk for the development of deep venous thrombosis leading to a potentially fatal pulmonary embolism. It is vital to appreciate this risk and apply appropriate prophylaxis. Constant vigilance is required, as deep venous thrombosis and pulmonary emboli can develop and progress despite standard prophylactic measures. In unstable patients, more aggressive prophylaxis may be warranted, including the use of inferior vena cava filters. A high index of suspicion and a low threshold for screening and diagnostic testing will allow earlier recognition and treatment of this lifethreatening condition. Treatment decisions are based on clinical suspicion, diagnostic examination results, and the potential complications of difficult treatment modalities. PMID- 1862473 TI - Weaning from mechanical ventilation. AB - An understanding of respiratory physiology is helpful when weaning a patient from mechanical ventilation. Various criteria are available that assess pulmonary function and the patient's ability to breathe spontaneously. The majority of patients are weaned without difficulty, but a small percentage will require careful evaluation. A complete assessment of the patient is essential during the weaning trial. The mode of ventilation during weaning is less important than careful observation during the trial. Simple vital signs and physical findings remain some of the best indicators of success or failure. PMID- 1862472 TI - New modes of mechanical ventilation. AB - Mechanical ventilation is required by surgical patients for a number of different reasons. The methods available to ventilate patients have increased in the last few years. Some of these techniques have proved helpful, while a few remain investigational searching for an application. Surgeons dealing with critically ill patients must remain current with alternative methods of ventilation. PMID- 1862474 TI - Advances in pediatric surgical critical care. AB - The advances in pediatric intensive care outlined here point out the differences between children and adults that need to be considered when taking care of children with surgical diseases. In the past, advances in pediatric critical care have not kept pace with advances in adult care, but these and other new techniques have rapidly closed this gap in knowledge. PMID- 1862476 TI - [Nursing research--anything happens to us. Interview by Grethe Kjaergaard]. PMID- 1862478 TI - [Nursing research. How can we improve health?]. PMID- 1862477 TI - [Nursing research. What is the outcome of nurses' pregnancies?]. PMID- 1862479 TI - [Nursing research--no, to 'home-knitting'. Interview by Grethe Kjaergaard]. PMID- 1862475 TI - [Nursing research--he has taken philosophy for himself. Interview by Grethe Kjaergaard]. PMID- 1862480 TI - [Nursing research--PhD students in nursing just now]. PMID- 1862481 TI - [Nursing research--quality before quantity. Interview by Grethe Kjaergaard]. PMID- 1862482 TI - [Nursing research--some will do it]. PMID- 1862483 TI - [Nursing research--a researcher's everyday]. PMID- 1862484 TI - [Powerlessness and frustration]. PMID- 1862485 TI - [Negotiations '91--extraordinary congress recommends close compromise]. PMID- 1862486 TI - [Nursing research--an important piece]. PMID- 1862487 TI - [Community health nursing--we will blend in. Interview by Kirsten Bjornsson]. PMID- 1862488 TI - [Nursing research--the long road. Interview by Grethe Kjaergaard]. PMID- 1862489 TI - [Change-over--back to everyday]. PMID- 1862490 TI - [Radical change in nursing instructor's functions]. PMID- 1862491 TI - [Education of cancer patients will improve. Interview by Lars Peter Bergqvist]. PMID- 1862492 TI - [The fierce hunt for taxes]. PMID- 1862493 TI - [That will keep a long time. Interview by Teddy Osterlin Koch]. PMID- 1862494 TI - [Straight on an average]. PMID- 1862495 TI - [Botulism in cattle, a review]. AB - Botulism in cattle is reviewed in the present paper. General information concerning the aetiology and symptomatology of the disease is followed by a discussion of the epidemiological situation in the Netherlands. Since 1975 several outbreaks of botulism type C or D have occurred. Poultry litter in which toxic carcasses were present, was the most important source of the toxin. An increasing number of cases of botulism type D was reported in recent years, which was probably due to the fact that poultry is not susceptible to toxin type D and therefore the presence of type D toxin is difficult to recognise timely. In addition, atypical cases of type B botulism occurred in the Netherlands during the period from 1977 to 1978, which were caused by supplementary feeding of brewer's grains. Finally, the diagnostic problems, differential diagnosis, prevention, treatment and public health aspects are discussed. PMID- 1862496 TI - ['Lelystad agent'--the cause of abortus blauw (mystery swine disease)]. AB - An unidentified agent was isolated from samples of pigs affected with abortus blauw (also known as mystery swine disease). This agent, designated 'Lelystad agent', grows in cultures of pig lung macrophages. The agent was inoculated into eight pregnant sows which subsequently aborted or gave birth to weak or dead piglets. The agent was then isolated from these piglets, thus confirming that it is the causal agent of abortus blauw. PMID- 1862497 TI - [Veterinary pathology: a vital specialism within veterinary medicine]. AB - Pathology is by definition an entity of major importance in medical science. Within medical care, pathologists are involved in cytopathological, histopathological and post mortem examinations. The value of post mortem examinations is discussed with reference to the value of the autopsy within human medical science. In veterinary medicine, veterinary pathology has to be incorporated in highly qualified veterinary medical care, has to participate in the quality assessment and the quality control of veterinary medical care, and has to be involved in the required continuing education of veterinarians. In addition, veterinary pathology is involved in basic research and research with regard to human health control. PMID- 1862498 TI - [Conjunctivitis?]. PMID- 1862499 TI - [Antibiotic sensitivity of Pasteurella haemolytica in slaughter cattle]. PMID- 1862501 TI - [The Veterinary Service Board. Health and Welfare legislation for Animals]. PMID- 1862500 TI - [On deworming and diets]. PMID- 1862502 TI - [Equine monocytic ehrlichiosis (EME), a review]. AB - Serological surveys showed that equine monocytic ehrlichiosis (EME) occurs in the USA, Canada and Europe. The causative agent is Rickettsia Ehrlichia risticii, isolated for the first time in 1984. The clinical features of the disease are sluggishness, anorexia, colic and fever, possibly followed by watery diarrhoea. Complications of an infection with E. risticii are laminitis and abortion. Colitis of the ascending colon may be observed at autopsy. Following a positive serological diagnosis (IgM ELISA) of EME, treatment with oxytetracycline can be initiated. It is also important to restore the fluid and electrolyte balance by infusion. Prevention may be achieved by vaccination. PMID- 1862503 TI - [The immune system in poultry]. AB - The avian immune system is reviewed. The avian immune system differs from that of mammals, mainly in the presence or absence of lymphoid organ and in the histology of these organs, in the antibody response, in the generation of diversity of antibodies, and in the transfer of maternal immunity. The chicken immune system is mainly discussed, since most of the research on the avian immune system has been performed using this bird. PMID- 1862505 TI - [Lameness in cattle]. PMID- 1862504 TI - [Determination of immunity (?)/immune response (using serological techniques]. AB - The effective use of serological tests for the diagnosis of disease and/or infection depends both on the nature of the diagnostic problem and on the diagnostic value of positive and negative results of the test. In veterinary practice, diagnostic uses consist in (1) diagnosis in patients showing typical symptoms, (2) staging of the infection, (3) screening studies, and in patients showing typical symptoms, (2) staging of the infection, (3) screening studies, and (4) monitoring of effects of therapy. In quantitative tests for diagnostic purposes, the positive or negative value of the test may be established using either reference ranges in controls or longitudinal studies in single patients. When serological tests are performed for measuring immunity or susceptibility of animals to infection, the test(s) should be performed in conjunction with experimental challenge infection studies. This form of combined testing thus provides the levels of serum antibodies protective against disease. PMID- 1862507 TI - [Long-range viewpoint Agricultural Research 1991-1994 (1)]. PMID- 1862506 TI - [Pseudo-pregnancy and type diagnosis]. PMID- 1862508 TI - [New reproduction and breeding techniques]. PMID- 1862509 TI - [Health care of domestic animals]. PMID- 1862510 TI - [The Veterinary Service Board. The Health and Welfare legislation for animals]. PMID- 1862511 TI - [Antibiotics]. PMID- 1862512 TI - [Attacks of apnea in an infant with achondroplasia]. AB - Infants and children with achondroplasia are at increased risk of sudden death because of apneic attacks caused by compression of the medulla oblongata or spinal cord by a constricted foramen magnum or narrow upper cervical spinal canal. This history of an infant with achondroplasia is discussed. As a result of apneic attacks she developed severe brain damage. Cervicomedullary compression was revealed at CT-scan and NMRI of the basicranium and upper cervical canal, and confirmed at decompressive surgery. Early symptoms can be clues to the existence of cervicomedullary compression. These clues are indication for further investigations. Decompressive surgery has good results when performed at an early stage. Knowledge of the signs and symptoms of cervicomedullary compression and of factors which increase the risk of complications are important in the management of achondroplastic patients. PMID- 1862514 TI - [A new variant of Munchausen's syndrome by proxy: the father in an active role]. AB - The case is described of an eleven-year-old boy with abdominal pain and hematuria. The hematuria appears to be fabricated by the father of the boy by adding cooked meat to the urine samples. The medical history of the father is very suspect for the Munchhausen syndrome. The case of the son differs in some respects from the normal pattern of the Munchhausen by proxy syndrome: the age of the son, the role of the father as active inducer and the low social class of the family. PMID- 1862513 TI - [A patient with the homozygote form of familial hypercholesterolemia]. AB - The history of an 11 year old boy with homozygous familial hypercholesterolemia with therapeutic response to cholesterol lowering drugs is presented. Symptoms, laboratory diagnosis and therapeutic problems are discussed. PMID- 1862515 TI - [The syndrome of the incarcerated left renal vein (nutcracker syndrome)]. AB - Gross hematuria with abdominal pain may be caused by entrapment of the left renal vein between the aorta and the superior mesenteric artery. In the urinary sediment the erythrocytes are normally shaped, making a renal parenchymatous cause unlikely. Ultrasonography shows a decrease of the diameter of the left renal vein of more than 50%, in every position of the patient. Cytoscopy a chaud reveals hematuria pouring out only from the left ureter. In this paper four patients with this syndrome are presented. PMID- 1862516 TI - [Meconium peritonitis: diagnosis, etiology and treatment]. AB - Fetal intestinal perforation causes a sterile inflammatory reaction of the peritoneum called meconium peritonitis. Twelve patients studied in the perinatal period serve to describe the classical fetal and neonatal signs and symptoms, the iconographical findings, treatment and prognosis. All but one infant, with a meconium pseudocyst, presented with the fibro-adhesive variety. Two were caused by cystic fibrosis, two by organic obstruction, one by fetal appendicitis and another two by ischemic necrosis of part of the ileum. In one of the latter two, the probable mechanism was feto-fetal embolisation following the in utero death of a co-twin. One idiopathic perforation, diagnosed in a preterm infant, healed spontaneously. The neonatal mortality rate was 18%. Primary enteric anastomosis was feasible in 3, Bishop-Koop anastomosis in 2 and an intestinal stoma in two others. Apart from the two survivors with cystic fibrosis, seven have no late gastro-intestinal sequelae. PMID- 1862517 TI - Electrical treatment of venomous bites and stings. PMID- 1862519 TI - Tryptophan residues of phospholipase A2 from the venom of an Australian elapid snake (Pseudechis australis). AB - Tryptophan residues 31 and 69 (Trp-31 and Trp-69) in phospholipase A2 (Pa-11) from the venom of an Australian elapid snake, Pseudechis australis, were modified with N-bromosuccinimide (NBS) or with 2-nitrophenylsulphenylchloride (NPSC1). NBS oxidized only Trp-31, whereas NPSC1 reacted with both Trp-31 and Trp-69. Treatment of the enzyme with NBS at various pH values resulted in losses of enzymic and lethal activities. No protective effect on the oxidation with NBS was observed by the addition of calcium ion (20 mM) or lecithin (4 mM). The observations suggest that Trp-31 is exposed to the surface of the molecule, composes a part of the lipid-water interface recognition site around the active site and is essential for enzymic activity. Calcium ion addition to the solution caused a change in ultraviolet spectrum of the native enzyme Pa-11. The difference spectrum indicates that a charge effect caused a typical tryptophan blue shift in the Ca(2+)-enzyme complex. Pa-11 oxidized with NBS showed a smaller ultraviolet absorption difference on the addition of Ca2+ ion. The results show that the hypochromic effect induced upon the binding of Ca2+ is due to perturbation of the specific tryptophan residue (Trp-31) which is involved in the active site. Dissociation constant, Kd, of the Ca(2+)-enzyme complex was calculated to be 3.4 x 10(-4) M at pH 8.0. PMID- 1862518 TI - Lethal potency and fractionation of Duvernoy's secretion from the brown tree snake, Boiga irregularis. AB - The liquid secretion contained only 15% protein and had relatively low proteolytic activity. The reconstituted crude secretion had a murine i.p. LD50 of 10.33 mg/kg and was not hemorrhagic in doses up to 200 micrograms. Fast Protein Liquid Chromatographic (FPLC) cation exchange analysis of reconstituted crude secretion resulted in resolution of 16 peaks. Lethal activity was identified in three peaks. The major lethal fraction was 12.5% of the secretion protein and had a murine i.p. LD50 of 7.3 mg/kg. A pooled fraction containing two lethal peaks which comprised 9.4% of secretion protein had moderate proteolytic activity and produced myoglobinuria in mice. The fraction had an approximate murine i.p. LD50 of 3.7 mg/kg. Microscopic examination of muscle tissue from mice succumbing to this fraction revealed multifocal myofiber degeneration and necrosis. SDS-PAGE indicated that the major lethal fraction contained three proteins with mol. wts of 12,500, 18,000 and 52,000 and the myotoxic fraction contained two proteins with mol. wts of 14,500 and 17,000. While B. irregularis Duvernoy's secretion has a low lethal index, it does contain a myotoxic fraction with moderate lethal potency. These observations and recent data describing clinical envenomation of several infant patients suggest that large specimens may pose a hazard to infants and small children. PMID- 1862520 TI - Immunochemical cross-reactivity of two phospholipase A2 neurotoxins, agkistrodotoxin and crotoxin. AB - Polyclonal rabbit antisera were raised against the phospholipase A2 neurotoxin agkistrodotoxin (AGTX) from Agkistrodon blomhoffii brevicaudus venom and against the phospholipase A2 subunit (component-B, CB) of crotoxin from Crotalus durissus terrificus venom. Anti-AGTX antibodies cross-reacted strongly with crotoxin and crotoxin-like molecules and more weakly with other phospholipases A2 from the venoms of Viperidae and Crotalidae. On the other hand, anti-CB antibodies cross reacted with AGTX, and also recognized ammodytoxin A and the phospholipase A2 from Vipera berus venom, but not other phospholipases A2 from Crotalidae and Viperidae. Anti-AGTX and anti-CB antibodies were able to inhibit the phospholipase A2 activity and to neutralize the lethal potency of the homologous and heterologous toxins (AGTX or crotoxin). Immunoaffinity chromatography columns were used to isolate anti-AGTX antibodies which recognized CB (91% of the total anti-AGTX antibodies), and anti-CB antibodies which recognized AGTX (52% of the total anti-CB antibodies). Immunochemical investigations performed with each type of antibody indicated that the majority of AGTX antigenic determinants are present on crotoxin component-B and on phospholipases A2 from Viperidae venoms, and that some of these determinants are involved in the neutralization of lethal potency and in the inhibition of enzymatic activity of AGTX and crotoxin. PMID- 1862522 TI - A non-radioactive receptor assay for snake venom postsynaptic neurotoxins. AB - A non-radioactive assay was developed for detecting the binding of postsynaptic neurotoxins to acetylcholine receptor (AchR) from Torpedo californica. Enzyme linked immunosorbent assay (ELISA) wells coated with long or short chain neurotoxins specifically bound to purified AchR while crotamine or two different cardiotoxins did not. Bound receptor was detected by antibody against AchR. Specificity was determined by dose-response experiments and competition studies using carbamylcholine chloride, acetylcholine chloride, or Naja naja atra cobrotoxin mixed with receptor. PMID- 1862521 TI - Amino acid sequence of a myotoxin from venom of the eastern diamondback rattlesnake (Crotalus adamanteus). AB - The complete amino acid sequence of a myotoxin isolated from Crotalus adamanteus venom (CAM-toxin) was determined. The total number of amino acid residues was 45, giving a mol. wt of 5202. The amino acid sequence was compared with those of previously determined Crotalus myotoxins. The CAM-toxin shows a surprisingly close relationship to those of peptide c (C. v. helleri), myotoxin a (C. v. viridis), crotamine (C. d. terrificus), myotoxin I and II (C. v. concolor) with homologies of approximately 98, 83, 90, 95 and 91%, respectively. The hydropathy profile of the CAM-toxin is almost identical to peptide c and myotoxin I, as can be assumed from the sequence homology. Despite the absence of any close sequence homology with the myotoxic phospholipase A2 enzymes, CAM-toxin contains a similar cationic myotoxic region at residues 2-10 as found in the other five myotoxic peptides. PMID- 1862523 TI - Pharmacological study of the muscle paralyzing activity of the juice of the banana trunk. AB - Extracts of the juice of the banana trunk were assayed in the isolated phrenic nerve-diaphragm muscle preparation of the rat. The chemical composition of those producing muscular paralysis was then studied. As active extracts mainly consisted of monopotassium oxalate, the effect of this compound on the muscle preparation was investigated and compared with that of the active extracts. The pattern of muscular paralysis induced by monopotassium oxalate was the same as that seen with the juice extracts. Likewise inhibition of contractions of the tibialis muscle was observed in vivo after intra-arterial administration of both the crude concentration of the juice and monopotassium oxalate. These findings suggest that monopotassium oxalate could be responsible for the muscular paralysis caused by the juice of banana trunk. PMID- 1862524 TI - Amino acid sequence of a muscarinic toxin deduced from the cDNA nucleotide sequence. AB - We prepared a cDNA library from venom glands of the green mamba Dendroaspis angusticeps. A cDNA clone was isolated using an appropriate nucleotide probe. The nucleotide sequence codes for a 21 residue signal peptide followed by a 65 residue protein having the amino acid sequence of muscarinic toxin 2, as confirmed in the accompanying paper (Karlsson, E., Risinger, C., Jolkkonen, M., Wernstedt, C. and Adem, A.). The cDNA encoding the muscarinic toxin has been compared with those encoding other snake toxins. There are close similarities with short-chain curaremimetic neurotoxins. PMID- 1862525 TI - Amino acid sequence of a snake venom toxin that binds to the muscarinic acetylcholine receptor. AB - The green mamba, Dendroaspis angusticeps, has two protein toxins that bind to the muscarinic acetylcholine receptor. The sequence of muscarinic toxin 2 was determined with an automatic gas phase sequencer. The C-terminal residue is Asp as determined by hydrazinolysis and amino acid analysis. Toxin 2 has 65 amino acid residues and a formula weight of 7040. It is homologous to a large number of other snake venom toxins as short alpha-neurotoxins, cardiotoxins/cytotoxins and angusticeps-type toxins of mamba venoms. The sequence is confirmed in the accompanying article (Ducancel, F., Rowan, E.G., Cassart, E., Harvey, A. L., Menez, A. and Boulain, J.-C. Toxicon 29, 516-520, 1991). PMID- 1862526 TI - Serum kinetics of crotoxin from Crotalus durissus terrificus venom in mice: evidence for a rapid clearance. AB - We report on an ELISA for the detection of crotoxin with a detection limit of 1-3 pg/ml of sample. Cross-reactivity with other animal venoms occurred only at concentrations above 1 microgram/ml. Serum kinetics of crotoxin were investigated in BALB/c mice after a single 10 micrograms s.c. dose of venom obtained from Crotalus durissus terrificus. Crotoxin levels were 254 +/- 141 ng/ml serum (X +/- S.E.) 15 min after venom injection, 3.9 +/- 0.5 ng/ml serum at 30 min and undetectable thereafter. The rapid clearance of crotoxin from the serum suggests that the test may be unsuitable for the clinical management of envenomation victims. PMID- 1862527 TI - The unique Duvernoy's secretion of the brown tree snake (Boiga irregularis). AB - Recently, bites by the colubrid Boiga irregularis (brown tree snake) in infants and young children on Guam have produced severe systemic reactions which bear some resemblance to classical manifestations of neurotoxic venom poisoning. This study demonstrates that the Duvernoy's secretion which elicits these reactions is a remarkably simple venom secretion with comparatively low toxicity and generally weak enzymatic activity. The intravenous LD50 for Swiss-Webster mice was approximately 80 mg/kg; significant neurotoxic manifestations were not observed in mouse trials. Deaths of lethally challenged mice occurred within minutes of injection, and appeared to result from cardiopulmonary crises. Duvernoy's secretion yields, protein content, enzyme activities, electrophoretic data and toxicity characteristics of the secretion are presented. PMID- 1862528 TI - Rapid isolation and partial characterization of two phospholipases from Kenyan Echis carinatus leakeyi (Leakey's saw-scaled viper) venom. AB - The purification and partial sequencing of two phospholipase A2 toxins from the venom of Kenyan E. carinatus leakeyi is described. The two proteins exhibit sequence homology with other toxic phospholipases. Both have a molecular weight in the region of 16,000 and are purified to homogeneity from crude venom by a single high performance liquid chromatography. The role of these proteins in the toxicity of the venom remains to be established. PMID- 1862529 TI - Tyrphostins as molecular tools and potential antiproliferative drugs. PMID- 1862530 TI - This and that: error, observation and education in pharmacology. PMID- 1862531 TI - Receptor classification using antagonists. PMID- 1862532 TI - Selectivity of ethanol on ligand-gated ion channels. PMID- 1862533 TI - Does carbon monoxide have a physiological function? AB - Recently endothelium-derived relaxing factor (EDRF) has been identified as nitric oxide. The source of the nitric oxide is L-arginine, and the L-arginine-nitric oxide pathway has been proposed to function as a widespread transduction mechanism for the regulation of cell function and communication. Gerald Marks and colleagues suggest that carbon monoxide, which is formed endogenously from heme catabolism and which shares some of the chemical and biological properties of nitric oxide, may play a similar role. This would be achieved by carbon monoxide binding to the iron atom of the heme moiety of soluble guanylyl cyclase and to the iron-sulfur centers of macrophage enzymes. PMID- 1862534 TI - Signalling targets for anticancer drug development. AB - Intracellular signalling pathways mediating the effects of growth factors and oncogenes on cell growth and transformation present a challenging new class of target sites for anticancer drug development. Several drugs are already available that may act in this way, including drugs that act on protein serine/threonine kinases, protein tyrosine kinases and phospholipase C, as well as inhibitors of myo-inositol signalling. As our understanding of the signalling pathways involved in growth control increases, new sites for pharmacological intervention will become apparent. Garth Powis reviews the evidence that this approach may eventually lead to new, more selective drugs for treating cancer. PMID- 1862535 TI - Therapeutic potential of ACAT inhibitors as lipid lowering and anti atherosclerotic agents. AB - Hypercholesterolemia is one of the few independent risk factors definitively linked to increased morbidity and mortality due to myocardial infarction. One possible therapy of current interest is the prevention of the absorption of dietary cholesterol by inhibiting the enzyme, acyl-CoA: cholesterol acyltransferase (ACAT), which catalyses the intracellular formation of cholesterol esters. Evidence is now accumulating that suggests that ACAT inhibition may not only lower plasma cholesterol levels, but may also have a direct effect at the artery wall, where ACAT has been shown to be responsible for the accumulation of cholesterol esters in arterial lesions. Drago Sliskovic and Andrew White discuss the importance of ACAT in the lipid transport system and the consequences of its inhibition in a variety of tissues, with emphasis on both lipid-lowering and anti-atherosclerotic effects. PMID- 1862536 TI - [Effect of delta-sleep peptide on the ultrastructural features of the rat sensomotor cortex]. AB - The performed studies have shown that injection of DSIP causes an activation of nuclear apparatus and plastic metabolism in III-Y layer of the rat cerebral cortex. The activation of axo-axon and axosomatic synapses indicates the modulation of inhibitory processes in the cerebral cortex. PMID- 1862537 TI - [Regeneration of the rat aortic intima in the region of a microsurgical suture]. AB - Intimal regeneration in the region of microvascular suture of the rat aorta was investigated by LM, SEM and TEM. Endothelial integrity was restored by endothelial cells from the defect edges. No thrombotic masses took part in the formation of the intimal thickening. It is supposed that the core of the intimal thickening formation is a transition of regenerating smooth muscle cells along elastic "railes" from media into intima. PMID- 1862538 TI - [A new case of trisomy in cattle]. AB - The new type of trisomy (2n = 61, XX, +19) was found in the heifer with prognathia inferior syndrome. Correlations between trisomy of different types and phenotypic abnormalities are discussed. PMID- 1862539 TI - [A rare case of long Y-chromosome arm deletion in a patient with sterility]. AB - A patient with complete or almost complete absence of long Y-chromosome arm is described. Basic clinic characters are low height, absence of developmental anomalies, phychosexual identification, aspermia, sterility. PMID- 1862540 TI - [Meiosis in Pleurotus florida Fovose]. AB - It is stated that the meiosis of Pleurotus florida differs from the classical one. The condensation chromosomes conjugate in metaphase I. PMID- 1862542 TI - [The first experiments which related DNA to genetics]. PMID- 1862541 TI - [In situ hybridization in human genome mapping]. AB - The methodological possibilities of non-radioactive in situ hybridization of nucleic acids and its application for an immediate localization of genes and chromosomes are discussed. The advantages of a non-isotope probe labeling versus a use of radioactive substances are emphasized. Various types of compounds used as a label are distinguished. The principles of use of the above labels and the ways to improve the method in terms of increasing its sensitivity are considered. Some results obtained while using non-radioactive labelled probes are reported. It is shown promising to use this method for molecular-genetic analysis of DNA polymorphism in human genome. PMID- 1862544 TI - The exponential-Gompertzian tumor growth model: data from six tumor cell lines in vitro and in vivo. Estimate of the transition point from exponential to Gompertzian growth and potential clinical implications. AB - The published growth data were examined for six tumor cell lines (FSA, Line 1, MCA-11, EMT6/RO, MGH-U1, MLS) grown in vivo and in vitro as monolayer cultures and as multicell spheroids cultured under different experimental conditions. Serial estimates of tumor sizes were fitted by Gompertzian equations obtained with a non-linear computerized program. When the growth equations of the same tumor growing in different experimental conditions were compared, the Gompertzian parameters alpha 0 (initial specific growth rate) and beta (retardation factor) showed a strong linear correlation in all the examined lines, with no exception. This occurrence supports the exponential-Gompertzian growth model, where an early exponential phase (which is virtually not influenced by exogenous factors) is followed by a Gompertzian phase, the characteristics of which are greatly dependent on environmental conditions. The transition between the two phases was estimated to occur when tumor size reached 10(2)-10(4) cells, depending on the cell line. This kinetic change in tumor growth may be clinically relevant as regards cytotoxic treatments. It could explain some consequences of delays in adjuvant (postoperative) chemotherapy observed in clinical trials on primary breast cancer. PMID- 1862545 TI - Establishment of a human medulloblastoma cell line (BO-101) demonstrating skeletal muscle differentiation. AB - A permanent cell line, BO-101, was derived from a classic vermian medulloblastoma in a 9-year-old child. This line grew in vitro in adherent cultures and grew in athymic mice as serially transplantable intracranial and subcutaneous xenografts. Intracranial neoplasms grew as masses of small cells, which focally showed large cells with intense immunoreactivity for desmin, myoglobin and alpha-striated actin. The rhabdomyoblastic nature of these cells was confirmed ultrastructurally. The primary neoplasm showed immunoreactivity for synaptophysin, neuron-specific enolase and vimentin. A large panel of monoclonal antibodies and antisera against neuronal and glial antigens failed to show glial and neuronal immunoreactivity in the cell culture and xenografts. Despite the marked genotypic and phenotypic differences, the original neoplasm and the cell line share a common chromosomal marker del (12) (p 13.1). The BO-101 line differs phenotypically and genotypically from previously established medulloblastoma cell lines and further supports the heterogeneous biologic properties of the cell populations that constitute these neoplasms. PMID- 1862546 TI - Morpho-functional study of vascular fluorochrome delivery to lung and liver metastases of Lewis lung carcinoma (3LL). AB - The growth of 3LL liver and lung metastases related to its vascular organization was studied by morphological and functional methods, using the Hoechst 33342 fluorescent DNA staining technique. Experimental liver and lung metastases were produced in syngeneic C57BL/6 mice by injection of 3LL tumor cells into a lateral tail vein or into the spleen, respectively. The resulting neoplasms were composed of large cells arranged in sheets with a thin irregularly distributed stroma. Scattered blood vessels with an open or closed lumen were observed within the tumor. Functional study of H33342 diffusion showed a single and reticular fluorescent pattern in liver metastases. In contrast, in lung metastases the fluorochrome diffusion revealed two different fluorescent patterns related to the location of the metastasis. Thus, parenchymal and subpleural metastasis presented a fluorescent pattern similar to that observed in the liver whereas metastases located around blood vessels and conducting airways never displayed fluorescence. In summary, our results suggest that the target metastatic organ and/or intra organ location modulates the characteristics of metabolic exchange of the tumor cells in relation to the vascular organization of the metastatic focus. PMID- 1862543 TI - A rapid in vivo bioassay for the carcinogenicity of pesticides. AB - Eight pesticides were tested in a bioassay based on the induction of preneoplastic lesions in the liver. Rats were given diethylnitrosamine intraperitoneally at 200 mg/kg bw and two weeks later were treated with pesticides for six weeks and then killed; all rats had a partial hepatectomy at week 3. Hepatocarcinogenic potential was assessed by comparing the number and area of glutathione s-transferase (placental form) -positive foci in the liver with those of controls given diethylnitrosamine alone. Positive results were seen with Chinomethionat, Phosmet and Propiconazole; the results obtained with Captan and Prochloraz were borderline; Benomyl, Daminozide and Folpet gave negative results. Our findings provide enough experimental evidence to indicate that great care should be exercised in the use of these compounds. PMID- 1862547 TI - Neuroendocrine effects of subcutaneous interleukin-2 injection in cancer patients. AB - Intravenous interleukin-2 (IL-2) administration has been shown to influence several hormonal secretions. The present study was carried out to investigate the endocrine effects of subcutaneous therapy with IL-2. Six patients with advanced renal cancer were studied. They were treated subcutaneously with IL-2 according to the schedule proposed by Atzpodien et al. Venous blood samples were collected at O-time and 1, 8 and 12 hours after the first IL-2 pulse of 9 X 10(6) IU/m2 at 8.00 a.m.; on a separate occasion, samples were collected during a saline infusion only. In each blood sample, serum levels of cortisol, beta-endorphin, GH, PRL, FSH, LH, TSH and the pineal hormone melatonin were measured by RIA. Both cortisol and beta-endorphin significantly increased after IL-2 injection. GH rose but not to a significant extent. PRL, FSH, LH and TSH did not change after IL-2. Finally, melatonin levels markedly decreased after IL-2 injection in the only 2 patients with elevated concentrations of this hormone before the start of immunotherapy. These results suggest that the endocrine effects of subcutaneous IL-2 therapy are similar to those previously described with intravenous administration. PMID- 1862548 TI - Combination chemotherapy with vinblastine, BCNU and cisplatin in advanced malignant melanoma. AB - A combination chemotherapy including vinblastine (6 mg/m2 i.v. days 1-2), BCNU (100 mg/m2 i.v. day 3), and cisplatin (50 mg/m2 i.v. day 5) was given as salvage treatment in 46 consecutive, previously treated patients affected by metastatic malignant melanoma. Courses were planned every 4 weeks provided that a complete bone marrow recovery occurred, otherwise they were delayed for 1-2 additional weeks. Objective responses (3 CRs and 10 PRs) were observed in 13/46 (28%) patients; 12 cases had stable disease and 21 patients progressive disease during treatment. Median duration of response was 13 months (range, 5-18), and median survival was 11 months (range, 3-20) for all patients. Nausea and vomiting were the most distressing side effects, whereas a grade I leukopenia caused a delayed treatment in 90% of patients. In conclusion, the combination chemotherapy was moderately toxic and did not seem to give substantially better results than obtained with other reported regimens. PMID- 1862549 TI - Influence of mitoxantrone on the syntheses of DNA and proteins of mouse tissues. AB - In view of the structural similarity of mitoxantrone to anthracyclines and its ability to intercalate into DNA, we studied its influence on the synthetic processes of DNA and proteins in CD-1 mice tissues. By studying at the DNA level the impairment of 3H-thymidine incorporation and its return to normal, it was found that bone marrow and spleen showed similar behavior, i.e., a rapid return to normal, which occurred before bone marrow cell number and spleen weight returned to basal values. At the cardiac level, the incorporation values of precursors into DNA, reduced by treatment with mitoxantrone, came back very slowly to the control ones. Hepatic DNA showed a lower sensitivity to mitoxantrone. Analysis of 3H-leucine incorporation into three protein fractions of the heart showed that the contractile proteins were the most responsive fractions to mitoxantrone treatment. Experiments on CD-1 mice treated repeatedly with mitoxantrone revealed that the antitumor drug, at the cumulative dose of 8 mg/kg i.v., induced alterations in myocardiac morphology similar qualitatively to those induced by doxorubicin, although smaller quantitatively. PMID- 1862550 TI - Mitoxantrone as a single agent in pretreated metastatic breast cancer: effects on T lymphocyte subsets and their relation to clinical response. AB - Mitoxantrone (DHAD), an anthracenedione with antineoplastic properties similar to doxorubicin, was tested for therapeutic efficacy and for immunomodulating action on lymphocyte subsets in 16 metastatic breast cancer patients, 12 of whom had been previously treated with chemotherapy. DHAD was given intravenously at a dose of 14 mg/m2 every 21 days. To evaluate total T lymphocytes (CD3), T helper (CD4), and T suppressor/cytotoxic cells (CD8) and the CD4/CD8 ratio, venous blood samples were drawn before and after the first DHAD cycle. Moreover, in 8/16 patients, B lymphocytes (CD20), T suppressor cells (CD8+/CD57+), T cytotoxic cells (CD8+/CD57-), NK (CD16) and IL-2 receptor-expressing cells (CD25) were also measured at the same time. An objective tumor response was achieved in 5/16 (31%) patients and the response rate was significantly higher in patients pretreated with hormone therapy alone than in those pretreated with chemotherapy. No relation was found between clinical response and changes in the CD4/CD8 ratio. Neither the mean number nor the percentage of CD3, CDA and CD8 cells observed after DHAD were significantly different with respect to those seen before. In contrast, the mean number of T suppressor cells, B lymphocytes and CD25-positive cells was significantly lower after than before DHAD administration, whereas no difference was seen in NK cells. These results confirm in humans the immunomodulating properties of DHAD previously described in experimental conditions. However, the DHAD-induced changes in lymphocyte subsets do not seem to be related to the clinical response in breast cancer. PMID- 1862551 TI - High-dose epirubicin as a single agent in the treatment of patients with advanced breast cancer. A Hellenic Co-operative Oncology Group study. AB - Fifty-two women with advanced breast cancer were treated with 6 cycles of epirubicin. Even though the study was started with a dose schedule of 110 mg/m2 every 3 weeks, the average treatment interval was 26 days and the median weekly dose 78% of the protocol requirement. Forty-eight patients were evaluable for response; 3 achieved a complete remission which lasted for 17, 24 and 65 weeks, respectively, and 14 a partial remission. Median survival was 32 weeks. Toxicity included nausea/vomiting (68%), anemia (24%), leukopenia (37%), thrombocytopenia (8%), alopecia (81%), stomatitis (24%), diarrhea (14%), fever (19%) and fatigue (14%). Also 1 treatment-related death occurred and 2 cases of arrhythmia. Monotherapy with high doses of epirubicin has definite activity in advanced breast cancer and deserves further study in combination with hematopoietic growth factors which might allow a higher dose intensity. PMID- 1862552 TI - Experience with intrapleural natural beta interferon in the treatment of malignant pleural effusions. AB - Malignant pleural effusion is a common complication of cancer. Intrapleural beta interferon has been recently tested, and responses were obtained in about 1/3 of the patients without considerable side effects. We treated 22 patients with recurrent symptomatic malignant pleural effusions with intrapleural beta interferon at increasing doses (5-15 million units) for a maximum of three courses and obtained only two responses. In our opinion, this schedule cannot be recommended for routine use. PMID- 1862553 TI - Outpatient surgical treatment with CO2 laser in oral cancer: immediate and long term results. AB - The immediate and long-term results of excising squamous cell carcinoma of the oral cavity or lip by CO2 laser are analysed in 51 consecutive subjects treated as out-patients. From January 1982 to December 1989, 39 cases of T1 and 12 cases of small (less than 2.5 cm) non-infiltrating recurrences of squamous cell carcinoma were treated at the Istituto Nazionale Tumori in Milan. Complete removal was obtained in 44 instances, while in 7 cases cancerous margins were observed on the specimen; 5 of these underwent another wider treatment and 2 refused further therapy. Two of 39 T1 patients developed local relapses and 6/12 recurrent cancers relapsed again. Long term results are complicated by second primary cancers in 19 instances. Out-patient laser therapy is well accepted by patients and its use involves lowered direct and indirect health organisation and social costs. PMID- 1862554 TI - Hemoccult sensitivity estimate in a screening program for colorectal cancer in the Province of Florence. AB - The sensitivity of Hemoccult testing (HO) in a population-based screening for colorectal cancer was evaluated. HO sensitivity estimates were calculated as the ratio of screen-detected HO-positives to total screen or interval-detected cancers. Sensitivity was estimated according to 1, 2, and 3-year rescreening intervals. Corresponding estimates are 69.4%, 61.8% and 57.7%, respectively. No significant correlation was observed between HO sensitivity and other variables, such as calendar period, tumor stage or site, or patient age or sex. HO sensitivity as estimated in the present experience is consistent with other reports of population-based screenings. Screening every year would achieve too limited an increase in sensitivity, compared to biennal screening, to be worth the difficulties of doubling organizational efforts and costs. PMID- 1862556 TI - Attendance to a screening program for cervical cancer in the city of Florence. AB - The study was aimed to assess: a) the proportion of true refusers among non attenders resulting from residents and screening database matching, b) the typology of refusers compared to attenders, and c) the reasons for non-attendance as stated by refusers. Three hundred and forty-one non-attenders according to computer-produced lists were interviewed: 29 were not evaluable, 148 had had a Pap test, 18 had not attended for valid reasons, and 146 were true refusers; 94 refusers accepted the interview as far a points b) and c) were concerned. Ninety four attenders, matched by age and residence, were interviewed for comparison. Attendance at private laboratories or incorrect identification of subjects on the screening record accounted for 45% or 55% of misclassified cases, respectively. The adjusted true refusal rate in the last 10 years was 18.1% compared to a computer-assessed non-attendance rate of 40.7%. Refusal was significantly associated to socioeconomic status (geographic origin, working activity and educational level of both women and husbands), whereas no significant association was observed for sexual history (deliveries, age at first sexual relation, number of partners) or health-related behavior. Attendance and counseling at the gynecologist's office were strongly associated to attendance, and gynecologists should be stimulated to promote opportunistic screening. The belief that screening is useless in the absence of symptoms, the fear of cancer being detected, postponement or laziness were the reasons for non-attendance stated by 80% of refusers. Improving knowledge about the purpose of the Pap test should be the main goal of any action aimed to improve screening attendance. PMID- 1862555 TI - Patterns of large bowel cancer by subsite, age, sex and marital status. AB - Incident cases of large bowel cancer from the Swiss canton of Vaud over the period 1974-88 were analyzed in relation to the distribution of site by sex, age, marital status and detailed subsite. A total of 1,968 cases were registered in males and 1,958 in females, corresponding to overall age-standardized (world) rates of 32.2/100,000 males and 22.4/100,000 females. The frequency of ascending and transverse colon cancer was lower in males (18.2% and 9.3%) than in females (23.1% and 10.0%, respectively), but cancers of the sigmoid colon and rectum were proportionally more frequent in males (34.0 and 30.0% versus 29.9 and 24.6% in females). Anal cancer accounted for 4.0% of large bowel cancers in females, but only 1.2% in males. Analysis of age-specific rates showed comparable values for ascending colon cancer in both sexes and in relation to each subsequent age group, as well as in sigmoid and rectal cancers up to middle age, while a male excess for the latter cancers became evident after age 55. A female excess for anal cancer was apparent in any subsequent age group. Information on marital status was available on 2,398 decreased subjects. Never married cases accounted for 12.2% of women and 8.1% of males. The excess of unmarried women was somewhat larger in the colon than in the sigma and rectum groups, but there was no evidence of excess of never married females for anal cancer. These data confirm that there are appreciable intersex heterogeneities in the descriptive epidemiology of various subsites of large bowel cancer, as well as complex interactions between sex and age, which may be related to female hormone correlates of intestinal carcinogenesis. Whatever the main biological mechanism(s), these data show noticeable similarities for both sexes in the descriptive epidemiology of cancers arising in the left colon and rectum, but noticeable differences with the right colon. Even more substantial are the differences with anal cancer, which should be linked to its venereal correlates. PMID- 1862557 TI - Epithelial-myoepithelial carcinoma of the parotid gland: a clinico-pathologic and immunohistochemical study of seven cases. AB - Seven cases of epithelial-myoepithelial carcinoma of the parotid gland are reported. Immunohistochemical evidence for the dual (glandular secretory and myoepithelial) differentiation of the cells composing these lesions is presented. Three of the cases recurred locally and two gave rise to metastases. The biologic behavior does not appear to be correlated with the histologic features that constitute the morphologic spectrum of epithelial-myoepithelial carcinoma. PMID- 1862558 TI - Skin metastasis of ovarian cancer: report of three cases. AB - Three cases of skin metastases in patients with ovarian cancer are reported. The late onset of skin metastases in the course of the disease represents an advanced stage accompanied by intraperitoneal spread and has a poor prognosis. Diagnosis and differentiation from herpes zoster and other skin tumors were based on histologic examination. Palliation of symptoms and partial local response were achieved by electron beam irradiation. PMID- 1862559 TI - Total circulating B lymphocyte abnormalities in a primary cerebral localization of non-Hodgkin lymphoma: a case report. AB - The authors describe a case of primary central nervous system lymphoma in a 43 year-old male. Interest in this rare form of B-lymphocyte non-Hodgkin's lymphoma is due to its increasing incidence in the last decade, especially in immunodeficient patients. Extraneural involvement was excluded by staging examinations: bilateral bone marrow biopsy from the posterior iliac crest, bipedal lymphography, abdominal CT scan, skeletal, thoracic and gastrointestinal X-rays, spinal puncture, ORL and clinical examination. The peripheral immunologic state was particularly interesting: there was a substantial decrease in total circulating B-lymphocytes at diagnosis (4.4% = 80/mmc; nv 13 +/- 4% = 287 +/- 130/mmc) and a further decrease after 2 and 4 months of therapy (0.16% = 2/mmc). Three months after completion of therapy, the B-lymphocyte level returned to the base level at diagnosis (7% = 88/mmc). At 10 months after diagnosis and 3 months after completion of chemotherapy, the patient is alive and in good health except for the after-effects of a left hemiparesis. The etiologic and possible pathogenic factors are considered. PMID- 1862561 TI - [Carotid endarterectomy in carotid stenosis--when is surgery indicated?]. PMID- 1862560 TI - Muir-Torre syndrome: a case report. AB - The authors present a case of Muir-Torre syndrome, the "sporadic" form, with a review of the literature. The importance of the close scrutiny of these patients and their relatives is stressed. PMID- 1862562 TI - [Rehabilitation of patients with apoplexy. Possibilities, duration and effect]. AB - A close relationship exists between the severity of a stroke and the functional level that can be obtained after rehabilitation. The goal of rehabilitation, therefore, should be based on the severity of the stroke. Remission mainly takes place (more than 80%) within the first three months post stroke. Remission after six months is very rare. Age and side of hemiparesis do not seem to influence the effect of rehabilitation significantly. It is not elucidated whether the severity of the stroke influence the effect of rehabilitation. Most of the controlled and the randomized studies indicate that rehabilitation of stroke patients, especially in rehabilitation units, accelerate remission, reduces length of stay and gives rise to a lasting improvement of function. PMID- 1862563 TI - [HIV infection and the development of dementia]. AB - Progressive dementia has been described in AIDS patients as the most significant neurologic complication, related to HIV-1 infection directly rather than to opportunistic infections. As the virus seems to enter brain early in the course of infection, incipient dementia or subclinical cognitive impairment have been assumed to occur in otherwise asymptomatic HIV-1 seropositive individuals. A review of relevant neuropsychological studies indicates that this suspicion receives no support in large well-controlled studies. The natural history of AIDS dementia is still not clearly delineated, but encephalopathy seems to develop only with or after systemic immunosuppression. PMID- 1862564 TI - [Early amnion rupture or amniotic band syndrome]. AB - Early rupture of the amnion with resultant oligohydramnios and subsequent development of mesodermal bands between the chorion and the fetus can cause various deformities. The degree of deformity depending on the extent of the band formation and the gestational age at which this occurs. The condition may involve all parts of the fetus and comprizes a spectrum ranging from clinically insignificant small constricting bands on the extremities to large craniofacial and visceral defects which may be fatal and cause abortion. Prenatal diagnosis relies mainly on ultrasonic investigation, and the treatment--quo ad vitam- consists mainly of reconstructive surgery. A case is reported. PMID- 1862565 TI - [Cardiovascular manifestations of hypothyroidism]. AB - On the basis of a case history, the clinical and paraclinical manifestations of hypothyroidism are reviewed. Exertion dyspnoea without signs of cardiac insufficiency occurs frequently. The minute and stroke volume and heart rate are reduced. The blood pressure may rise (reversible) and hypertension may occur. The function of the left ventricle is reversibly reduced. A tendency to formation of exudates has been observed. X-ray of the thorax may revial massive relatively asymptomatic pleural exudates and cardiomegaly. Pericardial exudate occurs frequently and is demonstrated best by echocardiography. Inter- and intracellular deposits, infiltrations and fibroses have been demonstrated in the myocardium and these probably contribute to some of the non-specific, reversible ECG changes (low voltage, flattening/inversion of T waves, sinus bradycardia). The plasma concentrations of several different enzymes (including creatine kinase (CK), CK MB and LDH) may be raised in myxoedema. The reason for this is perhaps compromized membrane function in the skeletal muscle cells. The diagnosis of myocardial infarction in myoedema requires that CK-MB constitutes at least 6% of the total CK and that the increase is transient. In patients with coronary sclerosis, substitution treatment should be initiated carefully because the risk of ischaemic symptoms is otherwise considerably increased. It is not elucidated whether the hypothyroidism per se can increase atheroma formation. PMID- 1862566 TI - [Diagnosis of Pneumocystis carinii pneumonia in HIV-positive patients. The diagnostic value of induced sputum and exercise test]. AB - The object of investigation is to illustrate the values of two noninvasive procedures: the induced sputum test and the exercise test in the diagnosis of Pneumocystis carinii pneumonia (PCP). Both of the procedures are described. Fifty HIV-positive men in whom interstitial pneumonia was suspected participated. PCP was diagnosed in 16 patients, in ten of these by the induced sputum test, the sensitivity of which is, therefore, 35-85% (95% confidence limits). The exercise test, an investigation for demonstration of exercise induced oxygen desaturation, was of good predictive value. Thus, seven out of nine patients with positive exercise test results had PCP as compared with two out of 19 with normal exercise test results, p = 0.0009. The sensitivity was thus 40-97%. In five out of the six patients with false negative results to the induced sputum test, the exercise test was performed and was positive in all of the case. The method is rapid and simple and merely requires access to an exercycle and a pulse-oxymeter preferably with a recorder. It is concluded that the exercise test and the induced sputum test are valuable investigations which supplement one another in cases of suspected PCP and which avoid the need for bronchoscopy in 53-80% of the patients. PMID- 1862567 TI - [Assessment of the surgical risk. Is the time between myocardial infarction and a possible surgical procedure of significance for a surgical risk?]. AB - During a five year period, 320 patients suffered from acute myocardial infarction (AMI) and within the next twelve months became candidates for surgery for either appendicitis (99 patients) or for a hip fracture (221 patients). An evaluation of the mortality at the second event (i.e. appendicitis or hip fracture) in relation to the time between AMI and second event, was done following the intention to treat principle. Appendicitis occurred with the same incidence during all 12 months following AMI. The second event mortality was independent of the time interval from AMI to second event. Age, infarction prior to index infarction and congestive heart failure were prognostically important in relation to second event mortality, but did not affect the constant second event mortality during the first year following AMI. Hip fracture occurred more often during the first months following AMI, where the second event mortality was highest. Congestive heart failure either prior to index infarction or at the index infarction was prognostically important in relation to second event mortality. The relatively high mortality in the first months after AMI could partly be explained by an association between congestive heart failure and hip fracture in the first months after AMI. We conclude that the "operative" mortality in patients with recent AMI is high. The mortality is related to congestive heart failure and not to the time between AMI and surgery. PMID- 1862568 TI - [Inguinal herniotomy by the Shouldice method. A follow-up study of 75 patients]. AB - A material of 78 patients with a total of 85 inguinal hernias was submitted to herniotomy by Shouldice's method. Following a median of observation of 15 months (range 4-23 months), clinical examination of 75 patients revealed two recurrences of the hernias corresponding to 2.4% (95% confidence limits 0.3-8.2%). On discharge from hospital, rapid and complete return to normal activities was recommended, as a rule immediately after removal of the sutures. In seven out of the 45 occupationally active patients, it proved necessary to observe special considerations while, in the 38 remaining occupationally active patients, the duration of sick-leave median only 11 days (lower and upper quartiles, eight and 24 days, respectively) after operation. PMID- 1862569 TI - [Accidents with power chain saws]. AB - During the three-year period 1987-1989, 80 persons were registered with lesions following accidents with chain saws. The information in the casualty department records was supplemented by an interview questionnaire. Sale of chain saws increased from the middle of the nineteen eighties although no appreciable increase in the number of accidents was registered. One of the reasons for this may be the legislation concerning safety equipment which was introduced in the middle of the nineteen eighties. Further efforts are still required to reduce the number of accidents. On the basis of the results of the investigation, the following suggestions are made: 1. Written information about personal protective equipment should be issued to every purchaser of a chain saw. 2. An informative campaign about the correct use of the chain saw and the personal protective equipment. 3. Compulsory issue of personal protective equipment in connection with hire of a chain saw. 4. Safety gloves should be included in the safety requirements. PMID- 1862570 TI - [Observer variation and accuracy in the clinical diagnosis of ascites]. AB - Seventeen observers participated in an observer variation study of the clinical evaluation of ascites. In a blinded design, eight patients with diagnoses of liver disease were examined. Fourteen observers examined the patients twice in order also to estimate the intra-observer variation. The accuracy of the observers' statements was compared with ultrasound findings, by which mean ascites was demonstrated in two patients. Poor correspondance between the observers' gradings and volume estimations, and poor accuracy of the gradings, make qualitative and quantitative ascites estimations useless. The inter-observer agreement was found to be low although the intra-observer agreement was good. The observers' subjective certainty of correctness of their own findings, marked as certain/uncertain, did not reflect the chance of making a correct statement on each particular occasion. The individual patient's general ability of inducing certainty did relate the chance of forming a correct diagnosis. Ultrasonic investigation of the abdomen is recommended in all situations in which demonstration of ascites is essential to diagnosis or therapy. PMID- 1862571 TI - [Epicrises from a department of medical gastroenterology]. AB - The content of discharge letters is important to general practice in order to give an optimal physical, psychiatric and social treatment in view of ideal utilization of the resources in the primary health service. The content of 91 discharge letters from a medical department of gastroenterology was judged by the general practitioner. Most often medication on discharge (25%) and reason for referral (15%) were missing. Dissatisfaction was expressed about late receipt of discharge letters (median: 13 days), the lack of information given to the patients, medicine on discharge, as well as reasons for possible changes in medication. The quality and content of the discharge letter were evaluated as good on the whole (80%). It is concluded that the discharge letter should have a higher priority and, for example, training is necessary. Further investigations are needed to solve these problems. PMID- 1862572 TI - [Assessment of microbial growth in central venous catheters. Consequences of laboratory findings]. AB - The tips of 92 central venous catheters (CVK) cultured according to a method for semiquantitative assessment of microbial growth revealed positive findings (greater than or equal to 15 bacterial colonies) in 44 (48%) and in 22 cases monocultures were found. Blood culture was performed in 20 cases and, in eight cases, catheter-related bacteriaemia was found, six of these being caused by Staphylococcus aureus. Contact with the clinical department resultated in commencement or alteration of antibiotic therapy which was relevant to the results of culture was only administered in 10 out of 44 cases. This is perhaps connected with the fact that removal of the catheter is adequate treatment in the majority of cases. The relatively great laboratory work be compared with the modest therapeutic benefits. Culture from CVK should not be undertaken routinely but may be recommended on more limited indications: suspected septicaemia originating in the catheter and/or signs of local infection. Blood culture from a peripheral vein should always be performed simultaneously. PMID- 1862574 TI - [Hypoparathyroidism, pseudohypoparathyroidism and pseudopseudohypoparathyroidism]. PMID- 1862573 TI - [Epitheloid sarcoma--an overlooked diagnosis?]. AB - Epitheloid sarcoma (ES) is a malignant soft-tissue tumour which occurs particularly on the hand and forearm in young adults. The tumour grows slowly and metastasizes relatively late but has, nevertheless, a considerable mortality and morbidity because it is frequently erroneously diagnosed, both clinically and pathologically, either as a benign tumour or as a reactive inflammatory process. Two typical cases with diagnostic delays of 12 and 15 years, respectively, which required amputations through the upper arm or forearm are described. Even although ES is a rare tumour form, clinicians and pathologists should be aware of this possibility as, in the early stages, the tumour can frequently be treated effectively and radically by wide local excision without amputation. PMID- 1862575 TI - [Blood pressure determination among school children]. PMID- 1862576 TI - [Registration of wound complications]. PMID- 1862577 TI - [Use of antiasthmatic agents in Denmark during 1979-1989. Do we overuse antiasthmatic drugs?]. PMID- 1862578 TI - [Routine hospital autopsy. Pro et contra]. PMID- 1862579 TI - [Health problems among persons exposed to grain dust]. AB - This review describes health problems in persons primarily exposed to grain dust. The main epidemiological investigations from the nineteen seventies and eighties are reviewed. The commonest complaints were mucus membrane irritation. In the majority of investigations, an excess incidence of chronic bronchitis was encountered and it cannot be disproved that asthma developed in a number of the employees. Influenza-like symptoms compatible with the organic dust syndrome have been described in several investigations from silos but allergic alveolitis has not been described in this branch. The latter condition has been encountered in farm workers working with mouldy grain. With dust concentrations of about the Danish threshold limit value, many health problems still occur. The following prophylactic measures are recommended: Effective drying of corn before storage, effective ventilation and cleaning and covering of dusty working procedures. Epidemiological investigations are proposed in the Danish raw material sector to illustrate health problems related to grain dust. These investigations should be combined with qualitative and quantitative occupational hygienic measurements of dust. PMID- 1862580 TI - [Felty's syndrome]. AB - Felty's syndrome (FS) consists of the triad: rheumatoid arthritis (RA), leukopenia and splenomegaly. FS occurs in approximately 1% of patients with RA. In this syndrome, the risk of infection is increased and anaemia, thrombocytopenia and cutaneous ulcers are more frequently observed. The literature is reviewed on the basis of a case history. The pathogenesis is unknown but is probably multifactorial. Cell antibodies, increased occurrence of immune complexes, inhibited neutrophil production, altered neutrophil distribution and reduced neutrophil function have been observed. The main indication for treatment is present if the patient has severe neutropenia (less than 0.1 x 10(9)/l) and repeated infections. Various methods of treatment are available. The most important are: gold, low-dose methotrexate, lithium, methylprednisolone pulse therapy, penicillamine and splenectomy. According to the literature, conventional steroid treatment cannot be recommended. PMID- 1862581 TI - [The Angelman syndrome. Does the phenotype depend on maternal inheritance?]. AB - Angelman's syndrome was described by Angelman in 1965 and since then 222 children with the syndrome have been reported: this paper reviews the clinical and cytogenetic features of these children and describes three further children with the syndrome. About one half of the cases have a cytogenetically visible deletion involving the long arm of chromosome 15, del (15) (q11-q13). Thus the deletion is cytogenetically similar to the one found in some Prader-Willi syndrome patients, but it differs in parental origin, being maternal in Angelman's syndrome and paternal in Prader-Willi's syndrome. Perhaps then genomic imprinting has an important impact on the development of these very different phaenotypes. A new symptom is keratoconus. The Angelman syndrome is associated with ocular and general hypopigmentation and in future studies this should be included in the clinical examination, thereby elucidating the possible role of the proximal chromosome 15 in the development of the neural crest. PMID- 1862582 TI - [Refusal of autopsy in hospitals. Development in the municipal hospital of Arhus after the enforcement of the new legislation]. AB - The frequency of refusal for autopsy by relatives of the deceased was investigated in Arhus Municipal Hospital before and after revision of the Danish legislation concerning these matters. The frequency of refusals increased from 28.9% to 49.8%. Energetic efforts by clinicians and pathologists are required to reverse this trend. PMID- 1862583 TI - [Causes of death in patients with cerebral neoplasms]. AB - The case records of 41 patients with cerebral cancer and their death certificates were reviewed with the object of investigating clinicians' causal reasoning. No really clear impression could be obtained. The case records did not contain any reflections about clinical or paraclinical conditions which might be related to conceptions of causality. The death certificates contained errors and deficits which were so serious in 44% of the cases that the death certificate presented an erroneous picture of the cause or causes of death. Minor errors were encountered in further 19% of the death certificates. These involved logically untenable statements of causes in 11 certificates (27%), statements about conditions which were not in agreement with the reports in 13 cases (32%) and errors in the statements about duration in ten cases (24%). These results scarcely express doctors' causal reasoning but rather that there is no uniform conception of how death certificates should be completed. PMID- 1862584 TI - [Should athletic injuries be treated with non-steroidal anti-rheumatic agents (NSAID)? Tenoxicam, piroxicam and placebo in the treatment of acute stress induced injuries]. AB - A total of 212 patients with acute sports injuries were allotted at random to treatment with 20 mg tenoxicam daily, 20 piroxicam daily or a placebo for ten days. The injuries could be subdivided into six groups: Tendinitis, periostitis, sprains, tendovaginitis, epicondylitis and muscular ruptures. Treatment was well tolerated and analysis of the total material showed a slight but significantly better effect in the group treated with the active drugs. More detailed analysis revealed that this increased effect was produced by a definitely better therapeutic result in the group of patients with tendinitis treated with non steroid anti-inflammatory drugs (NSAID) while, in the other types of injury, no definite effect could be observed. On the basis of these observations, the authors conclude that acute tendinitis may be treated with NSAID (tenoxicam) while the question is not yet solved where other acute stress-induced injuries are concerned. PMID- 1862585 TI - [Reproducibility of a rapid test for HIV antibody]. AB - This study evaluated three rapid test kits for HIV antibody detection. Thirty consecutive blood specimens from the infectious diseases outpatient clinic were examined by three house officers who tested each specimen twice in a blind and randomized experiment. HIV-Chek (Du Pont) and HIV-1/HIV-2 TestPack (Abbott) were easy to handle and gave good intra- and interobserver agreement and good agreement with routine ELISA. Recombigen (BioScience) was difficult to interpret and gave poorer intra- and inter-observer variation. We suggest that HIV-Chek and TestPack can be used for assessment of patients' HIV antibody status in emergency circumstances with only minimal instruction of the staff. PMID- 1862586 TI - [Computed tomographic cholangiography. An alternative non-invasive diagnostic method in ductus choledochus calculi]. AB - Computed tomographic cholangiography has not been mentioned as a diagnostic procedure in the demonstration of common bile duct calculi. Computed tomographic cholangiography demonstrated both calcified and non-calcified common bile duct calculi in two patients. Computed tomographic cholangiography can be employed in investigation of biliary tract disease in selected cases where endoscopic retrograde cholangiography is not possible and ultrasound and ordinary computed tomography fail. PMID- 1862588 TI - [Nutrition training in medical education]. PMID- 1862587 TI - [Infantile myofibromatosis. A case of solitary type in a 6 months old male]. AB - A case of infantile myofibromatosis in solitary form occurring in Denmark is presented. The tumour was situated in the right inguinal region and had resulted in occlusion of the femoral vein and involvement of the lymph glands. The diagnosis is established histologically by demonstration of noduli of cells resembling myofibroblasts arranged in bundles and fasciculi. Once the diagnosis is established an expectant attitude may normally be assumed. PMID- 1862589 TI - [Research, prevention, accomplishments]. PMID- 1862590 TI - [Tympanic membrane prosthesis using soft magnetoelastomer]. AB - This paper presents a new method for tympanum prosthesis application. The prosthesis is fixed by the interaction of magnetic pondermotive forces between two soft petals of a magnetoelastomer. This type of prosthesis was applied to 30 patients with dry perforative otitis media, aged 51-75 years. The intervention was performed in the outpatient department. Prostheses are recommended to be replaced every 3 months. These patients showed good tolerance of the treatment, which significantly improved their hearing level. The method of prosthesis fixation was reliable and atraumatic. PMID- 1862591 TI - [Variation pulsometry during surgery of Vidian nerve]. AB - This paper describes a method for assessing the efficacy of Wilde's incision based on mathematical analysis of cardiac rhythms. In patients with chronic polypous rhinosinusitis, the parasympathetic nervous system tonicity is found to be predominant. After Wilde's incision through a transmaxillary subperiosteal approach cardiac rhythms change, suggesting the predominance of sympathetic innervation. PMID- 1862592 TI - [Clinical aspects of anatomy of the nervous apparatus of the pharyngoesophageal junction]. AB - By examining extraorgan innervation of the pharyngeal-esophageal junction of adult cadavers, it was found that the risk of injury of the superior laryngeal nerve and its branches was very high during larynx resection and extirpation, lateral pharyngotomy, thyroid gland resection according to the method of A.V. Martynov, and Crile's operation. Esophageal branches of the recurrent laryngeal nerve or the inferior laryngeal nerve can be damaged during larynx extirpation or strumectomy according to the method of O. V. Nikolaev. The nervous apparatus of the pharyngeal-esophageal junction consists of nerve bundles located in the adventitia, muscular layer, and submucous base. PMID- 1862593 TI - [The functional status of the thyroid gland and adrenal cortex in newborn babies and infants with acute ethmoiditis]. AB - Using the RIA method, thyroxine (T4), triiodothyroxine (T3), and cortisol (C) were measured in 10 patients with acute ethmoiditis, aged from 13 days to 6 months. At the peak of the disease, i. e. when infection toxicosis was very manifest, T3 was significantly lower and T4 tended to decrease. During the convalescence period T3 increased distinctly and T4 continued to decline. It can be concluded that the thyroid function was inhibited during the toxic period; however, this inhibition was transient and required no intervention. Nevertheless, in the case of complications, especially sepsis, transient hypothyrosis may develop which requires substitution therapy. Variations in cortisol serum concentrations were insignificant. PMID- 1862594 TI - [Therapeutic effect of helium-neon laser on microcirculation of nasal mucosa in children with acute and chronic maxillary sinusitis as measured by conjunctival biomicroscopy]. AB - Using biomicroscopy of the bulbar conjunctiva, 65 patients, aged 6 to 15 years, with catarrhal and purulent forms of acute and chronic maxillary sinusitis were examined. At the repair stage the patients were exposed to laser therapy. The results give evidence that laser therapy produced a positive effect on microcirculation and reduced the potential of relapses. Low-energy helium-neon laser affected mostly vessel permeability (decrease of perivascular edema) and blood rheology (red blood cell aggregation). In terms of circulation changes, laser therapy was more beneficial in the case of acute maxillary sinusitis. Circulation lesions, that persisted after laser therapy in some patients with chronic maxillary sinusitis, can be attributed to stable morphological changes in the wall architectonics of microvessels of the nasal mucosa. PMID- 1862595 TI - [Clinical course of mastoiditis as reported by the specialized emergency care hospital]. AB - In the last decade diverse clinical manifestations of mastoiditis have been reported. This paper describes specific features of the clinical development, diagnostic value of individual symptoms, and complications in 90 cases of mastoiditis treated in the otorhinolaryngological department of the Clinical Hospital for Emergency Medical Care, city of Sverdlovsk, during 1984-1988. The observations allow the conclusion that during acute otitis media the duration of mastoiditis development reduced and many classical symptoms of mastoiditis, e. g. protrusion of the posterior-superior wall of the external acoustic meatus, profuse purulent discharge from the ear, hyperemia, swelling of the behind-the ear area, occurred less frequently. The incidence of such life-threatening complications as meningitis and meningoencephalitis increased noticeably. It means that the list of indications for hospitalization of patients with acute otitis media should be extended. PMID- 1862596 TI - [Diagnosis and treatment of congenital defects and abnormalities of the nasal cavity in children and adults]. AB - In 300 patients with congenital defects and abnormalities of the nasal cavity development, physiological functions of the nose were investigated, using advanced methods, e. g. rhinofibroscopy, microrhinoscopy, rhinopneumometry, olfactometry, thermometry of the nasal mucosa, and pH measurement of the nasal mucus. Disorders in respiratory, olfactory, and protective functions were revealed. This led to surgical intervention in more than 300 cases. Original methods and modified procedures were developed as applied to specific pathologies. Physiological measurements before and after surgery demonstrated that correction of development defects and abnormalities of the nasal cavity contributed to the recovery of nose functions. PMID- 1862597 TI - [Classification of congenital defects of larynx]. AB - A classification of congenital malformations of the larynx was developed on the basis of 61 observations. All the malformations were subdivided into organ (20 cases) and tissue (41 cases) defects. Organ congenital malformations of the larynx included: dysgenesis of the cartilage stroma, dystopia, and vascular lesions. Tissue congenital malformations of the larynx included: dysplasia, hypoplasia, and dyschronia. The most severe form of organ malformations was dysgenesis of the cricoid cartilage that required surgical intervention in all cases. The most frequent form of tissue malformations was dysplasia (24 cases) of connective, cystic (polypous), or mixed type. Every form of congenital malformations of the larynx are described, and their specific features and prognosis are discussed. PMID- 1862598 TI - [Videolaryngoscopy and videolaryngostroboscopy in phoniatrics]. AB - Clinical applications of videolaryngoscopy (VLS) and videolaryngostroboscopy (VLSS) in phoniatrics were investigated. Altogether 150 patients with functional and organic lesions of the larynx and 50 normal subjects representing "voice" specialties were examined. Measurements of vibration, amplitude, frequency and oscillation asynchronicity of vocal cords yielded objective information about vibration in the norm and at pathology. VLS and VLSS can help identify functional and organic diseases of the larynx, document various pathological processes, evaluate the condition of the vocal apparatus, and compare pre- and postoperative laryngoscopic pictures. These methods can find application in training and therapeutic procedures for biofeedback purposes. PMID- 1862599 TI - [Electromyography of external laryngeal muscles in diagnosis of dysphonia]. AB - Bioelectrical parameters of two groups of external laryngeal muscles, viz. superior muscles pulling up and inferior muscles pulling down the thyroid cartilage, were measured. Hypokinetic dysphonia was indicated by 1.2-1.6-fold increase of the pulse amplitude of superior muscles and hyperkinetic dysphonia was evidenced by 1.4-2.0-fold increase of that of inferior muscles. When the amplitude was identical on differed by less than 1.2 times, mixed dysphonia was suspected. In healthy people, the pulse amplitude of inferior muscles exceeded that of superior muscles by 1.2-1.4 times. This approach helps to improve the accuracy and reliability of dysphonia diagnosis, to better understand mechanisms of the pathology, and to develop the most efficient methods of voice recovery. Altogether 60 patients and 30 normal subjects were examined. PMID- 1862600 TI - [Electronic glottography (clinical aspects)]. AB - In order to study the application of electronic glottography in clinical laryngology, 200 patients with different diseases were examined, using a glottographic unit, computer, oscilloscope, and a recorder. It was found that glottography is an objective method which can be applied to evaluate and detect disorders of vocal folds in different states. This method fails to determine the vibration capacity of an individual fold or diagnose laryngeal lesions without an additional examination. PMID- 1862602 TI - [Metastasis of laryngeal neoplasms after larynx resection]. PMID- 1862601 TI - [Secondary superior mediastinitis in otorhinolaryngology]. AB - The factors responsible for superior mediastinitis are described in 12 patients with inflammatory pathologies of ENT-organs, with emphasis on the anatomical topographic characteristics of the neck and mediastinum subcutaneous spaces. Clinical symptoms typical of anterior and posterior superior mediastinitis are summarized. Procedures of emergency treatment of secondary superior mediastinitis are described. It is emphasized that the first thing to be done is to treat areas of primary inflammation and thus to prevent infection propagation in the mediastinum. It is recommended to open the mediastinum as soon as possible and to drain it actively. It is also recommended to include reinfusion with autoblood of patients exposed to UV irradiation to the combined therapeutic protocols. PMID- 1862603 TI - [Treatment methods in keloid lesions of the ear]. PMID- 1862604 TI - [Improved method of ultrasonic diagnosis of maxillary sinus diseases in children]. AB - A modified technique of ultrasonic diagnosis of accessory nasal sinus diseases based on an analysis of the profile of echograms has been developed. A correlation between the profile and pathological changes in the Highmore antrum has been found. It has been shown that the cystic fluid has a characteristic difference between the intensity of the start and echo impulses. Echograms of a cyst and its capsule reveal that they are significantly heterogeneous. Pus is characterized by a pronounced ultrasound absorption, fluid pus and thick pus showing different response. Plasma and blood are characterized by a significant ultrasound absorption and sufficient homogeneity. An interpretation of an echogram obtained under clinical conditions is presented. PMID- 1862605 TI - [Noise pathology in otorhinolaryngology]. AB - Intensive industrial noise is an adequate stimulus of the hearing organ. Obviously, it can cause occupation-related hypoacusis in noise exposed workers. Pathological changes in other organs and systems that accompany cochlear neuritis are poorly studied; however, it seems that they have no noise-determined specific features. Clinical and provocative examinations have shown that noise, which exceeds maximal allowable levels, produces a significant effect on the development of the symptom-complex of pathological disorders, including hypoacusis, neurodynamic and neurocirculatory changes, hypertensive disease. Combination of disorders in the cardiovascular and central nervous function should be viewed as a pathology induced by intensive industrial noise, i. e. as an independent nosological form of pathology termed noise disease. PMID- 1862606 TI - [Clinical effectiveness of magnetolaser therapy of vasomotor rhinitis]. AB - Magnet-laser therapy was used to treat vasomotor rhinitis in 90 patients. A constant magnet of 50 mT was applied to the exterior of the nose, and an infrared laser beam was applied via a light-guide to the reflexogenic zones of concha inferior. The radiation power density was 5 mW/cm2. The magnetic exposure time was 6-10 min and the laser exposure time was 3-5 min for each half of the nose. The therapeutic course was 8-12 sessions. The therapeutic results depended on the type of vasomotor rhinitis, clinical disorders, and duration of the disease. Good results were seen in 84 (93.3%) patients out of 90 cases. Stable remission was recorded in 61.1% patients, significant improvement of clinical manifestations of vasomotor rhinitis was observed in 32.2% cases. Best results were reported in patients with autonomic forms of vasomotor rhinitis who suffered from short-term disease and vasodilation disorders. PMID- 1862608 TI - [Deontological aspects of occupational diseases in otorhinolaryngology]. AB - Medical deontology plays an important role in the improvement of medical care. Deontological aspects of occupational pathology in otorhinolaryngology are deeply involved in physician's activities, beginning with preliminary and regular medical examinations and ending with determination of the relationship between disease and occupation, development of therapeutic recommendations and subsequent rehabilitation. All these problems are of personal and social importance of which an ENT-doctor should always be aware. PMID- 1862607 TI - [Treatment of chronic rhinitis in children]. AB - This paper discusses involvement of intestinal dysbacteriosis in nasal inflammation. Altogether 42 children of preschool age with chronic rhinitis were examined. It was found that microbial changes in the nasal cavity were related to the degree of intestinal dysbacteriosis, which was detected in most patients. The drugs that were used in combined therapy to treat microbial changes in the nasal mucosa and intestine produced good clinical and bacteriological effects. The 4 month follow-up showed that the children on the combined therapeutic protocol remained in the remission stage throughout this time period, whereas 85 +/- 10% of the control children exhibited exacerbation of the inflammatory process in the nasal cavity within 2-3 weeks after onset of standard treatment. PMID- 1862609 TI - [Experience in teaching emergency care at the otorhinolaryngological faculty of the continuing medical training]. AB - In order to improve the expertise and special skills of ENT doctors dealing with urgent cases, the curriculum of advanced medical training courses (the city of Donetsk) has been modified to include several stages: evaluation of the qualification of students; lectures, seminars, practical lessons. This helps ENT doctors to be better prepared when coping with urgent cases, which in turn leads to lower lethality rate and more successful rehabilitation of patients. PMID- 1862610 TI - [Rhinocerebral mucormycosis]. PMID- 1862612 TI - [Retropharyngeal fibroma]. PMID- 1862611 TI - [A rare case of middle ear barotrauma]. PMID- 1862613 TI - [A rare case of development of tracheal granuloma after strumectomy]. PMID- 1862614 TI - [Original surgical approach in removal of laryngopharyngeal angioma]. PMID- 1862615 TI - [Orbital and intracranial complications of acute hemisinusitis in a 9-year-old child]. PMID- 1862616 TI - [A case of deep fungal infection of maxillary sinus and ethmoidal labyrinth]. PMID- 1862617 TI - [Mucocele of the maxillary sinus]. PMID- 1862618 TI - [Characteristics of emergency surgical technique in neck wound]. PMID- 1862619 TI - [Clinical importance of lipid peroxidation]. PMID- 1862620 TI - [Problem of classification of food poisoning]. PMID- 1862621 TI - [The role of carbohydrates in child nutrition]. PMID- 1862622 TI - [Prognostic significance of body weight and the possibility of dietary correction of obesity in male Moscow residents aged 40-59 years]. AB - Males, aged from 40 to 59, were followed up during 5 years after a standard epidemiological investigation. Their mortality rate and incidence of new cases of myocardial infarction and cerebral stroke were studied against the background of active preventive program (group I), and during routine treatment (group II). Hinh prognostic importance of body mass value has been shown in respect to common mortality rate, mortality rate due to cardiovascular diseases, incidence of myocardial infarction and its lethal outcomes. Difficulties in the correction of nutrition habits in middle-age subjects for decreasing their body mass, and relations between the nutrition habits and body mass were noted. Regardless of the body mass growth degree, a tendency was observed to the lowering of common and cardiovascular disease-induced mortality rates. The incidence rate of myocardial infarction in patients with excessive body mass significantly decreased. Body mass correction has been recommended in subjects aged from 40 to 49 years with body mass index 29. PMID- 1862623 TI - [Analysis of actual nutrition of vegetarians]. AB - The questionnaire method was used in the study of the actual nutrition of 20 vegetarians. A group of subjects who received mixed food were observed for comparison. The mean day ration of the two groups differed in the increased proportion of vegetables, fruit, milk products, nuts and vegetable seeds in the vegetarians' nutrition. The analysis of the chemical composition of the ration has shown that the absolute content of protein, fat, carbohydrates, some vitamins of group B in the vegetarians' nutrition is lower than the values recommended. Besides that this nutrition is deficient in Fe, Zn, vitamin B12. However, vegetarian rations with low calorie value are capable of providing physiological requirements of the body in food fibres, vegetable oil, beta-carotene and ascorbic acid. PMID- 1862624 TI - [Prevention of accumulation of strontium-90 in the bones by fortifying the food with fish products]. AB - The replacement of 1/5 part of the usual ration received by non-inbred white rats for fish mass containing up to 4 g/kg Ca resulted in a sharp (by 70%) reduction of Sr-90 accumulation after its oral intake. The effect is intensified in case of normalization of the basic ration in respect to Ca content, and the lowering of the isotope accumulation level in the skeleton comprises 82% as compared to the group of animals that received the Ca-deficient ration. PMID- 1862625 TI - [Incidence of cholelithiasis after its experimental induction by various methods]. AB - The incidence rate of cholelithiasis was studied in varying methods of lithogenic stimulation: a diet enriched with cholesterol and chenodesoxycholic acid, induction of acute aseptic inflammation of the gallbladder by thermal damage, and the use of ++anti-gallbladder sera. The results of the study have shown almost similar (44-52%) reproducibility of cholelithiasis in guinea pigs, the development of pigment concrements was recorded in the absolute majority of cases. Correlation of the cholelithiasis incidence rate with inflammatory disorders in the gallbladder has evidenced the importance of the immunoallergic component in the determination of acute cholelithiasis and cholelithiasis, where cholelithiasis shows its secondary character. PMID- 1862626 TI - [Biological value and assimilation of sarcoplasmic protein concentrates from commercial fish products and the effect of their consumption on rats]. AB - The biological value of 3 concentrates of sarcoplasmatic proteins from industrial fish (minthal, cod, putassu) was assayed in the 4-week experiment on growing male Wistar rats by the methods of counting the coefficients of protein effectiveness and pure protein effectiveness that comprised 100, 110 and 110% in relation to the corresponding parameters obtained with casein. The actual assimilation of the fish product proteins proved to be significantly higher than that of casein. Hypocholesterolemic and hypolipidemic effects of the protein products studied are, probably, caused by the presence of pectin. PMID- 1862627 TI - [Amino acid composition and biological value of pastries with protein-rich additives]. AB - The authors studied amino acid composition of confectionery (bisquits) enriched with dry fat-free milk, dried buttermilk, dry whey and soya bean flour. The biological value of the products was estimated by the sum of essential amino acids, by the ratio of essential amino acids and total nitrogen, by the chemical score and the variation coefficient of the amino acid score. It has been established that confectionery enriched with dry fat-free milk and dried buttermilk contain more lysine than those enriched with soya bean flour. The balance of amino acids is improved in the products enriched with dry fat-free milk and dried buttermilk. To improve the amino acid balance and increase protein content in food products it iz recommended that by-products of milk manufacturing be mildly used. PMID- 1862628 TI - [Chemical nature and biological activity of miliacine]. AB - Chemical nature and biological activity of miliacine that is contained in millet oil have been studied. It produces moderate anti-inflammatory effect, stimulates sexual resistance in female rats, increases summary gonadotropic activity of the hypophysis in infantile female rats; in case of acute intoxication with carbon tetrachloride, it promotes normalization of enzyme activity in the liver and blood serum. Miliacine is of practical importance in meat cattle breeding as a growth stimulator. With the use of miliacine the mean daily animal's gain in weight grows, and the coefficient of the food ration digestibility rises. In contrast to other growth stimulators used in cattle breeding miliacine possesses no toxic properties. PMID- 1862629 TI - [Experimental substantiation of rational protein consumption levels for different groups of the adult population in the USSR]. PMID- 1862630 TI - [Effect of a new exopolysaccharide on animal body]. AB - The influence of new exopolysaccharide, synthesized by Candida tropicalis and Pseudomonas sp. consortium in ethanol, on the animal body was studied in chronic experiments conducted in 200 non-inbred white rats. The animals were sacrificed after 3, 10 and 18 months of follow-up. The results of the investigations permit a conclusion that exopolysaccharide given to the animals during a long period does not produce a significant effect on the animal's growth and development, on the antitoxic function of the liver, on the parameters of protein, lipid and carbohydrate metabolism, on oxidizing phosphorylation in the mitochondria of the liver, and is low-hazard with respect to allergenic properties. PMID- 1862631 TI - [Estimation of nutritive value of foods based on the tables of their chemical composition]. PMID- 1862632 TI - [Hygienic evaluation of nitrate levels in drinking water and vegetable food products in various regions of Lithuania]. AB - Significantly higher nitrate content was detected in drinking water and vegetables grown by the rural population in the regions where industrial enterprises producing chemical fertilizers are located, as compared to the control regions. It has been concluded that a special attention should be paid to the daily level of nitrates ingested by the population (especially by children) in the industrial regions of the Republic and to their health state. PMID- 1862633 TI - [Nutritional structure and food habits of the population of one of the regions of Moscow]. PMID- 1862634 TI - [Urgent problems of Salmonella infections]. PMID- 1862635 TI - Synthetic oxygen transport fluids based on perfluorochemicals: applications in medicine and biology. AB - Recent advances in the development and assessment of synthetic oxygen transport fluids based on perfluorochemicals (PFCs) are reviewed. The basic properties of PFCs are outlined, together with the selection criteria for biomedical applications. PFCs must be emulsified for intravascular use and attention is focussed on the formulation and biocompatibility testing of both first- and second-generation emulsions and their components in man and other species. The multidisciplinary applications for PFCs in medicine and basic biomedical research are described, including the clinical use of Fluosol-DA 20% as an oxygen-carrying perfusate in percutaneous transluminal coronary angioplasty. PMID- 1862636 TI - Quality of red cell concentrates in relation to the volume of the buffy coat removed by automated processing in a top and bottom system. AB - The effect of automated removal of increasing volumes of buffy coat in a 'top and bottom' system on the composition of red cell concentrates (RCC) was investigated. The volume of the buffy coat was adjusted to group 1:50 ml (n = 31), group 2: 70 ml (n = 31) and group 3: 100 ml (n = 31), respectively. The numbers of platelets and leukocytes in the buffy coats were comparable between the groups, whereas the red cell volumes in the buffy coats showed a significant difference (17 +/- 3.6 ml group 1, versus 22 +/- 4.1 ml group 2 and 26 +/- 3.88 ml group 3; p less than 0.001). The volumes, hematocrits and cell counts of the RCC were not significantly different. The plasma volumes were inversely correlated with the volume of buffy coat removed, i.e. 268 +/- 19 ml group 1, versus 257 +/- 15 ml group 2 and 233 +/- 20 ml group 3 (p less than 0.001). We conclude that in the 'top and bottom' system an increase of the volume of the buffy coat from 50 to 100 ml did not improve the quality of the RCC regarding contamination with leukocytes and platelets. PMID- 1862637 TI - Clinical evaluation of the effects of storage time and irradiation on transfused platelets. AB - Platelet concentrates stored for up to 5 days at room temperature or irradiated with 15 Gy immediately prior to transfusion were evaluated for their ability to increase the platelet count in thrombocytopenic patients. Platelets irradiated with a dose of 15 Gy immediately prior to transfusion achieved corrected increments (CI) at 1 and 20 h after transfusion no different from those achieved by non-irradiated platelets. Storage for 5 days reduced the mean 1-hour CI to 5.7 compared with a mean of 12.3 achieved by platelets transfused after only 1-day storage (p = 0.008). Similarly, the frequency of a repeat transfusion being indicated within 24 h increased with increasing storage time (p = 0.005). PMID- 1862638 TI - Comparison of platelet-rich plasma collection using the Haemonetics PCS and Baxter Autopheresis C. AB - We have compared 118 platelet-rich plasma donations collected using the Autopheresis-C Platelet cell (Auto C) with 166 donations using the Haemonetics PCS. The median platelet yield from the Auto C was superior (2.51 vs. 1.54 x 10(11] although collection times differed (60 vs./40 min). There was greater variability in the platelet yield from the Auto C (0.45-5.6 vs./0.26-2.8 x 10(11], but leucocyte contamination was not significantly different. After secondary processing, there was significantly less residual platelet-poor plasma (272 vs. 369 ml). Platelet function assessed during 5 days of storage was satisfactory for both, although platelet aggregation responses to collagen and adenosine diphosphate were superior in the Auto C platelets. PMID- 1862639 TI - Low prevalence of antibodies against human immunodeficiency virus in Finnish haemophiliacs. AB - National yearly surveys were carried out between 1985 and 1989 to determine the prevalence of antibodies for human immunodeficiency virus (HIV) in Finnish patients with bleeding disorders. From 192 out of the 214 haemophiliacs (90%) tested, 2 patients were positive for anti-HIV. No seropositivities were found after 1985. Fourteen out of 21 patients (67%) with type III von Willebrand's disease, and 7 out of 8 patients (88%) with factor XIII deficiency were tested with negative results. The low prevalence of anti-HIV (0.94%; 2/213 tested), is mainly due to the self-sufficiency for clotting factors, the low prevalence of HIV in the population, and the use of cryoprecipitate during the critical period. PMID- 1862640 TI - Syphilis serology in blood donors: a possible surrogate marker for human immunodeficiency virus risk. AB - We report a preliminary study on whether syphilis serology might be reactive in some blood donors at risk for human immunodeficiency virus (HIV) infection. We retrospectively analyzed voluntary blood donations with reactive Treponema pallidum antibody (TPA) tests according to the type of donation, the presence of other safety markers, confidential unit exclusion, syphilis diagnosis, and HIV risk factors. Over 2 years (1987-1988), 1 in 8,900 regular homologous donations (n = 258,610) was TPA positive as compared with 1 in 2,200 directed donations (n = 6,685) and 1 in 300 autologous donations (n = 8,870; p less than 0.05 for both). The rate in directed donations was not significantly higher than in first time regular donors (1 in 4,800; n = 57,000). TPA-positive donations had higher rates of antibody to hepatitis B core antigen and confidential unit exclusion than TPA-negative donations. Ten TPA-positive homologous or directed donors had latent or previously treated syphilis (1 in 26,500 such donations), and 2 of these had HIV risk factors. None of the autologous donors were determined to have active syphilis. Syphilis serology in blood donors bears further scrutiny as a possible surrogate marker for HIV risk. PMID- 1862641 TI - Defining the specificity of anti-A/B IgM/G antibodies with different antigens and lectins. AB - The specificity of anti-histo blood group A/B antibodies is defined by the antigen used for their production and selection (in the case of mouse monoclonal antibodies, mAbs) or by the antigens present on various intestinal bacteria (for polyclonal human IgM and/or IgG, phAbs). Absorption experiments with red blood cells and free antigen have been used earlier to define specificity; here we use A/B substances of human, animal and synthetic origin as well as known reactivities of mAbs or lectins as tools to further characterize epitope properties of the A/B antigens. The signal response patterns obtained with identical phAbs anti-A/B IgM/G on three different antigens are superposable. In contrast, commercially available mAb anti-A/B IgM, when tested on the same antigens, revealed different response curves. The chemical specificity of lectins for distinct monosaccharides in terminal position was exploited to delineate the specificity of mouse ascites anti-A IgG1 and of phAbs anti-A/B IgM/G. Helix pomatia lectin inhibited the access of MB9 to porcine A almost completely whereas binding capacities of human anti-A IgM/G were inhibited by 50 and 62%, respectively. In similar experiments Bandeiraea simplicifolia lectin was seen to inhibit access of anti-B IgM/G to horse B by 34 and 58%, respectively. No inhibition was seen with lectin from Ulex europaeus or concanavalin A on plates coated with the three different A or B substances. Thin-layer chromatography (TLC) of antigens revealed one spot for the synthetic trisaccharides, whereas the human and animal blood group substances showed 2 and 3 spots, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1862642 TI - Antibody-coated erythrocytes induce secretion of tumor necrosis factor by human monocytes: a mechanism for the production of fever by incompatible transfusions. AB - The transfusion of incompatible red blood cells (RBC) rapidly results in the development of fever by an unknown mechanism. In this study, the human monocyte secretion of the endogenous pyrogens tumor necrosis factor (TNF) and interleukin 1 (IL-1) was measured. Exposure to human RBC sensitized with antibodies to D or Fya antigens induced the rapid secretion of TNF, but not IL-1. TNF secretion persisted when monocytes remained in contact with sensitized RBC, but returned to baseline several hours after removal of RBC. Thus, TNF secreted by monocytes may be a mediator of fever during the immune-mediated destruction of RBC in vivo. PMID- 1862643 TI - T lymphocyte colony assay in patients with idiopathic autoimmune hemolytic anemia: preliminary results. PMID- 1862644 TI - The red cell antigens Aua and Aub belong to the Lutheran system. PMID- 1862645 TI - Medical malpractice cases and awards: 1980-1990. PMID- 1862646 TI - Pressure sores: an overview and update. AB - Pressure sores are expensive and difficult to treat complications of immobility and the incidence of these lesions will increase as the population ages. Modalities for prevention and treatment are numerous but physicians often are not familiar with products available and lack a systematic approach to patients with pressure sores. This paper reviews factors involved with the formation of pressure sores and treatment modalities currently available. PMID- 1862647 TI - The medical dichotomy: malpractice. PMID- 1862648 TI - It's those doctors, not my doctor. PMID- 1862649 TI - Contact Nd:YAG laser for soft tissue surgery. AB - The contact Nd:YAG laser is an effective tool for head and neck soft tissue surgery for its precision, predictability, and touch technique. Understanding of its biophysics, precaution and application expedites operation, enhances surgical results and shortens hospitalization. PMID- 1862650 TI - Salmonella D enteritis in the newborn: a maternal infant case study. AB - This is a case of a 31-year-old pregnant female who had diarrhea one week prior to delivery and was later diagnosed as having Salmonella D. This report also discusses the physical changes in the neonate within 48 hours post delivery and medical treatment for Salmonella D. PMID- 1862651 TI - The role of the FDA in new drug development and availability. AB - During the last decade, the process by which the FDA regulates investigational new drugs has become a renewed focus of national attention. The ability of the FDA to maintain a balance between accelerating the availability of new drugs and ensuring that patients do not receive unsafe or ineffective treatments has been particularly challenged by the AIDS crisis. In response to this crisis, the FDA has revised its regulations and created various formal mechanisms for expediting the development and accessibility of promising new therapies to treat AIDS and other serious illnesses. Regulatory requirements have been reduced and consultation with the FDA to discuss the planning and design of clinical research is encouraged. PMID- 1862652 TI - Difference of opinion on HB 2461, midwife bill. PMID- 1862653 TI - [Study on ursodeoxycholic acid biotransformation by three strains of clostridia]. AB - Using the improved TLC procedure, we measured the conversion rates of ursodeoxycholic acid(UDCA) from chenodeoxycholic acid (CDCA) by 3 strains of clostridia--C. perfringens HS-10, C. butyricum DL-20 and LQ-29 isolated. The orthogonal test was used to determine the optical conditions of biotransformation for HS-10. It was found that the conversion rate of UDCA by HS-10 was over 80% during 6-48 h in RCM medium containing 0.2 mmol/L CDCA. The UDCA conversion rates were still over 70% when the CDCA concentrations were as high as 0.8-1.0 mmol/L. In addition, the WW-BCP (Waste water from bean curd production) without any supplemental nutrients was preliminarily proved to be a potential inexpensive conversion medium. PMID- 1862654 TI - [Studies on the antitumor antibiotic aclacinomycin A]. AB - During the course of screening for new antitumor antibiotics, a new anthracycline antibiotic--aclacinomycin A was separated from the broth and mycelium of Streptomyces AC-57. The strain AC-57 was isolated from the soil collected in the Shanghai suburbs. According to its culture and physiological characteristics the producer was identified as Str. galilaeus AC-57. The broth and mycelium were extracted and treated with solvents as usual way. The aclacinomycin A was separated by silica-gel column chromatography eluted with chrolo-form-methanol. Aclacinomycin A, its aglycone and sugar components were identified by comparison of their physico-chemical and spectral data (MS, UV, IR, 1H-NMR, and 13C-NMR) with authentic compound, purified from the market sample. PMID- 1862655 TI - Comparison of the rat liver microsomal metabolism of the enantiomers of warfarin and 4'-nitrowarfarin (acenocoumarol). AB - 1. Rat liver microsomal metabolism of the enantiomers of warfarin and acenocoumarol (4'-nitrowarfarin) has been studied. The enantiomers of both compounds were hydroxylated mainly at the 6- and 7-positions. Acenocoumarol enantiomers were much better substrates for cytochromes P-450 than the corresponding warfarin enantiomers; Km values for the 6- and 7-hydroxylations were 2 to 19 times lower for R- and S-acenocoumarol than for warfarin. 2. Formation of the 6-, 7-, and 8-hydroxy-metabolites of warfarin was stereoselective for the R-enantiomer (the R/S ratio for total intrinsic clearance was about 3). 4'-Hydroxylation was not stereoselective. In contrast, formation of acenocoumarol metabolites was stereoselective for the S-enantiomer (the S/R ratio for total intrinsic clearance was about 3). 3. From the effects of phenobarbitone and methylcholanthrene induction, and inhibition by cimetidine, on in vitro metabolism of the enantiomers of both compounds, it was concluded that the differences between warfarin and acenocoumarol can be explained partly by the involvement of different enzymes. PMID- 1862656 TI - The influence of charge transfer complex formation on the antibacterial activity of some tricyclic drugs. AB - 1. Phenothiazines and structurally related drugs are effective in eliminating bacterial plasmids. 2. Charge transfer complex formation between chlorpromazine and xanthine dyes with different electron acceptor activities (e.g. fluorescein, eosin, erythrosin and rose bengal) was detected by differential spectrophotometry. Charge transfer complexes were formed between the strong electron acceptor rose bengal and various tricyclic drugs. 3. On the basis of the wavelength shift, the binding energies of drugs and dyes were estimated. 4. The temperatures dependence of the reaction indicates charge transfer complex formation rather than a chemical reaction between drugs and dyes. 5. The anti plasmid action of the phenothiazines was decreased in the presence of xanthine dyes. As a consequence of competitive inhibition between bacterial binding sites and xanthine dyes, the binding energy of drugs in the plasmid replication system could be determined in the presence of dyes. 6. Drugs with binding energies in the range of 0.23-2.31 kcal/mol can inactivate the plasmid replication system. PMID- 1862657 TI - Metabolism of minaprine in human and animal hepatocytes and liver microsomes- prediction of metabolism in vivo. AB - 1. The metabolism of minaprine and its major metabolite p-hydroxyminaprine were studied using hepatocytes and liver microsomes from different species. Metabolism of this drug in vitro was then compared with in vivo data already published. 2. Our results showed that the major metabolic route (4-hydroxylation of the aromatic ring) is the same in the two experimental systems. Other in vivo biotransformation pathways (i.e. N-oxidation, reductive ring cleavage, N dealkylation, oxidation) were also confirmed in hepatocytes. 3. Similar inter species variability was observed both in vitro and in vivo. The present study has led to the same conclusion as previous in vivo metabolic investigations, namely, that metabolism in the dog quantitatively differs from that observed in other animal species. 4. These results clearly demonstrate that in vitro models (i.e. isolated hepatocytes and liver microsomes) are powerful tools in predicting the metabolic pathways of a drug in man and animal species. PMID- 1862658 TI - Liver slices in dynamic organ culture. I. An alternative in vitro technique for the study of rat hepatic drug metabolism. AB - 1. Precision-cut liver slices in dynamic organ culture, a novel in vitro technique, is described and applied to the study of hepatic drug metabolism in the rat. 2. These slices catalysed the oxidative O-deethylation of the substrate, 7-ethoxycoumarin, over 6 h incubation. In addition, the direct conjugation of 7 hydroxycoumarin with either sulphate or glucuronic acid was maintained over 6 h. 3. The formation of 7-hydroxycoumarin and the presence of the sulphate and glucuronide conjugates in slices exposed to 7-ethoxycoumarin demonstrated integrated phase I and phase II drug metabolizing activities in this system. 4. Minor modifications of the incubation system allowed for the metabolism of four volatile chlorinated benzenes: monochlorobenzene 1,2-, 1,3-, and 1,4 dichlorobenzenes to aqueous soluble metabolites. 5. The use of liver slices in dynamic organ culture as an alternative preparation for the study of xenobiotic metabolism is discussed. PMID- 1862660 TI - Metabolism in the rat of a model xenobiotic plant metabolite S-benzyl-N-malonyl-L cysteine. AB - 1. The metabolism of a model xenobiotic plant metabolite S-benzyl-N-malonyl-L cysteine (BMC) administered to rat at 10 mg/kg has been studied using a combination of radio-t.l.c. and h.p.l.c. 2. The major route of excretion for the administered 14C was via the urine (79% in 3 days). 3. The major metabolite was hippuric acid. The extent of biotransformation of BMC indicated the lability of the N-malonyl bond whose hydrolytic removal initiated a metabolic sequence which involved the action of C-S lyase to produce benzyl thiol. 4. A comparison of the findings from this study with those from experiments with N-acetyl-S-benzyl-L cysteine and S-benzyl-L-cysteine is made to support the metabolic pathway proposed. PMID- 1862659 TI - Liver slices in dynamic organ culture. II. An in vitro cellular technique for the study of integrated drug metabolism using human tissue. AB - 1. Precision cut human liver slices in dynamic organ culture have been used to study the integrated metabolism of 7-ethoxycoumarin and the conjugation of 7 hydroxycoumarin. 2. The metabolism of 7-ethoxycoumarin and 7-hydroxycoumarin was monitored for 6 h. For both substrates there was a time-dependent increase in metabolites present in the incubation medium. The low levels of free 7 hydroxycoumarin found in the medium when 7-ethoxycoumarin was the substrate suggests good coupling of phase I and phase II metabolism. 3. With suitable incubation conditions, i.e. change of medium containing new substrate every 2 h, the metabolism of both 7-ethoxycoumarin and 7-hydroxycoumarin by human liver slices was found to proceed at similar rates for up to 24 h. This was demonstrated using five separate human liver preparations. 4. Human liver slices also metabolized mono-chlorobenzene and o-, m- and p-dichlorobenzene to aqueous soluble metabolites. There was a time-dependent increase in the appearance of aqueous soluble metabolites present in the incubation medium. Metabolites were not retained by the liver slices. 5. A cold-storage transit buffer has been described and used to maintain the levels of drug metabolism in both rat and human tissue for periods of up to 6 h. 6. The use of human liver slices in dynamic organ culture as a suitable method for the direct assessment of integrated hepatic drug metabolism is proposed. PMID- 1862661 TI - A novel metabolite of strychnine, 22-hydroxystrychnine. AB - 1. An unknown metabolite of strychnine termed M-5 was isolated, from an incubation mixture using guinea pig liver microsomes, by repeated preparative t.l.c. 2. The structure of M-5 was shown to be 22-hydroxystrychnine by mass, n.m.r. and i.r. spectrometry. 3. 22-Hydroxystrychnine is a stable enol, a unique metabolite possessing a hydroxyl group on the double bond of the alicylic moiety. PMID- 1862662 TI - Contrasting systemic stabilities of the acyl and phenolic glucuronides of diflunisal in the rat. AB - 1. Diflunisal (DF) is metabolized in humans and rats primarily to its acyl glucuronide, phenolic glucuronide and sulphate conjugates. 2. After i.v. administration of DF acyl glucuronide to pentobarbitone-anaesthetized rats, DF and its phenolic glucuronide and sulphate conjugates appeared rapidly in plasma, indicating ready systemic hydrolysis of the acyl glucuronide and subsequent biotransformation of liberated DF. 3. Approximately 72% of the acyl glucuronide dose was recovered in bile and urine over 6 h: 52% as acyl glucuronide, 6% as phenolic glucuronide, 5% as sulphate, and 8% as isomers of the acyl glucuronide arising from intramolecular acyl migration. 4. Blockage of excretion routes by ligation of the ureters, bile duct, and both ureters and bile duct, decreased plasma clearance of the acyl glucuronide from 7.8 ml/min per kg to 6.0, 3.2 and 2.2 ml/min per kg respectively, and increased the apparent terminal plasma half life of DF from 2.1 h to 2.6, 3.4 and 6.3 h, respectively. 5. By contrast, DF phenolic glucuronide was quite stable after i.v. administration at the same dose. 6. This study shows that systemic cycling between DF and its acyl glucuronide exists in the rat in vivo, with portions of each cycle of unstable acyl glucuronide through DF yielding stable phenolic glucuronide and (presumptively stable) sulphate conjugate. PMID- 1862663 TI - The metabolism of 4-aminobiphenyl in rat. I. Reaction of N-hydroxy-4 aminobiphenyl with rat blood in vivo. AB - 1. 3H-4-Aminobiphenyl (ABP, 5 mg) given i.p. to rat had elimination half-lives of 15.6, 17 and 17 h, respectively, for urinary, faecal and total 3H elimination. 14C-ABP administered orally to rats at 100 mg/kg gave elimination half-lives of 31, 36.7 and 34 h, respectively, for urinary, faecal and total 14C elimination. 2. Semi-log plots of percentage dose remaining in the body versus time indicated that: (i) 82% of 3H activity was excreted in 36 h with a half-life of 14.4 h and 18% with a half-life of 46.2 h, and (ii) 77% of 14C activity was excreted in 48 h with a half-life of 15 h and 23% with a half-life of 180 h. 3. After i.p. injection of 10 mg/kg 14C-ABP to rats, ferrihaemoglobin (HbFe3+) concn increased to 60% in 2 h, accompanied by accumulation of 14C activity in erythrocytes, indicating that the active metabolite, N-hydroxy-4-aminobiphenyl (N-hydroxy-ABP) had oxidized haemoglobin-Fe2+ (HbFe2+) and was bound to the erythrocyte. 4. ABP given i.p. to rats at 0.24 mmol/kg rapidly appeared in blood, disappeared with a half-life of 30 min, and blood concn plateaued at 30 nmol/ml. The concn of 4 acetyl-aminobiphenyl (AABP) plateaued at 17 nmol/ml after 15 min, indicating a dynamic equilibrium between N-acetylation of ABP and N-deacetylation of AABP. The concn of 4'-hydroxy-4-acetylaminobiphenyl (4'-hydroxy-AABP) increased slowly at 1.65 nmol/h. 5. AABP given i.p. to rats at 0.88 mmol/kg slowly appeared in the blood, accompanied by the appearance of ABP and 4'-hydroxy-AABP and formation of HbFe3+. After 4 h the concn of AABP and ABP was 27-35 mmol/ml, indicating a dynamic equilibrium between N-deacetylation of AABP and acetylation of ABP. Neither N-hydroxy-ABP nor N-hydroxy-4-acetylaminobiphenyl (N-hydroxy-AABP) were found. PMID- 1862664 TI - [Clinical value of monophasic action potentials]. AB - The method of monophasic action potential (MAP) recording has experienced a significant surge in interest since the introduction of the contact electrode, which in contrast to the suction electrode, allows the safe and simple use of this technique in the clinical electrophysiology laboratory. MAP recording not only provide for a more precise determination of local activation, but most importantly, permit direct measurement of myocardial repolarization and action potential duration (APD), respectively. This had led to new insights into the cycle-length-dependence of the human APD, both in response to single extrastimuli and to steady-state heart rate changes. An advancement of the contact electrode catheter design now permits simultaneous pacing and MAP recording, and thereby, simultaneous determinations of APD and effective refractory periods (EPP) at the same endocardial site in the human heart. MAP recordings have demonstrated significant usefulness in the direct monitoring of antiarrhythmic drug effects, both in terms of dosage control and in the direct measurement of antiarrhythmic drug effects on the relationship between ERP and APD (ERP/ARD-ratio). Because MAP recordings reflect the local cellular electrophysiology, they also provide a more sensitive and precise index of myocardial ischemia than conventional ECG recordings. This can be utilized to assess the success of revascularizing procedures directly during or after the intervention. Recently, MAP recordings helped to discover early after-depolarizations in patients with "torsade de pointes", providing a possible explanation for the mechanism of polymorphous ventricular tachycardia in man. PMID- 1862665 TI - [Impaired diastolic ventricular function in dilated cardiomyopathy with variously reduced systolic function. A Doppler echocardiography analysis]. AB - Diastolic ventricular function was assessed by Doppler echocardiography in 50 patients with idiopathic dilated cardiomyopathy (DCM) and sinus rhythm. The patients were subdivided into two groups with either a moderately reduced ejection fraction (less than 32%; group 1, n = 25) or a severely reduced ejection fraction (less than 32%; group 2, n = 25), the latter having an unfavorable prognosis. The degree of heart failure according to the NYHA classification was more pronounced in group 2 (p less than 0.05). Mean pulmonary capillary wedge pressure (PCm) was also higher in group 2 (gr. 1:9.8 +/- 5.5 vs. gr. 2: 16.2 +/- 8.9; p less than 0.02), and the morphological parameters obtained by conventional M-mode echocardiography showed increased left ventricular volumes and mass in both groups with DCM, as compared with a control group (n = 16); there was a reduced volume/mass ratio in group 2. The parameters of systolic function derived from M-mode and Doppler echocardiography were reduced in patients with DCM, but were more pronounced in group 2. Doppler parameters of diastolic ventricular filling were differently affected in both groups with DCM. In group 1 there was a reduced contribution of the early diastolic phase to ventricular filling (FE/FA) (contr.: 2.29 +/- 0.99 vs gr. 1: 1.40 +/- 0.45; p less than 0.05) and a reduced early peak Doppler velocity, indicating an impaired ventricular relaxation. In group 2, as compared with controls and group 1, there was an increased ratio of early/late diastolic peak velocities (VE/VA) (contr.: 1.49 +/- 0.54 vs gr. 2: 2.32 +/- 1.37; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1862666 TI - [Detection of acute graft rejection with Fourier transformation of the surface ECG in long-term follow-up of heart transplantation]. AB - Up to now, diagnosis of acute rejection after heart transplantation (HTx) has been based on endomyocardial biopsy (EMB), but there is the need for reliable noninvasive parameters. Spectral analysis of the surface ECG with fast Fourier transformation (FFT) has been shown to be useful for rejection monitoring in the immediate postoperative phase. We tested the method in the chronic phase after HTx: the QRS complex (2 bipolar leads, position tattooed with Indian ink) was repeatedly analyzed with FFT (segment size 120 ms, 512 points. Blackman-Harris window) in 38 patients for 4-36 months after HTx. In mean intervals of 3 months, 254 checkups with FFT and EMB were performed on the same day. EMB revealed 28 acute rejection episodes in 21 patients, and ongoing rejection was diagnosed in 17 EMB. During rejection the frequency content of the QRS complex between 70 and 110 Hz increased in 25/28 rejection episodes (89%) and in 15/17 ongoing rejection cases, whereas in the time domain no specific changes could be seen. The QRS amplitudes did not reliably indicate rejection, but decreased slowly during follow-up. After therapy the spectral changes disappeared within weeks. No signs of acute rejection were evident in 209 EMB: in 156/209 frequency analyses (77%) the spectra were constant, in 45/209 cases the frequency content increased, and eight analyses could not be evaluated. As the number of rejection crises decreased in the first postoperative months, there was an increasing number of false positive FFT analyses (positive predictive value 35%). Thus, a change of frequency content requires control by biopsy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1862667 TI - [Localized 31 phosphorus NMR spectroscopy of the human heart--development of a measuring method and initial clinical application]. AB - In this work, the technique of 31P-NMR-spectroscopy is applied for the first time to diagnose coronary heart disease in patients, using a suitable measuring technique. In 13 healthy volunteers we applied a method comfortable and tolerable for patients, which enabled us to examine the myocardium inside the reception area of a surface coil. Concerning myocardium-specific selectivity and sensitivity the localization techniques FROGS (Fast-ROtating-Gradient Spectroscopy), 1-D-ISIS (1-Dimensional-Image-Selected-In-vivo-Spectroscopy) and 3 D-ISIS were compared. By a combination of the 3-D-ISIS-technique with magnetic resonance imaging, we obtained a monitored position of the volume of interest (VOI) within the myocardium, thus gaining a selective measurement. The cube shaped VOI with a lateral length of 50 mm was placed into the apical-septal area of the myocardium. On the basis of the obtained results, we examined seven patients suffering from coronary heart disease, which was symptomatic and verified by coronary angiography. The 31P-NMR-spectra of the two examined groups were computed into numbers representing the relative content of the myocardial high-energy-phosphates. In addition, the quotients PCr/ATP and Pi/ATP were calculated and compared. With this small number of cases the evaluation of the PCr/ATP-ratios already showed a significant difference of 0.34 (p less than 0.01) between patients with coronary heart disease (0.49 +/- 0.19) and healthy volunteers (0.83 +/- 0.27). The findings suggest the conclusion that 31P-NMR spectroscopy is able to be instrumental in the diagnostic detection assessment of the metabolic state in coronary heart disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1862669 TI - [The effect of PTCA on clinical outcome in patients with coronary single vessel disease]. AB - We evaluated a 3-year clinical follow-up in 53 patients with unsuccessful PTCA, due to failure to reach the lesion (control-group) in comparison to a "matched pairs" group of 53 patients, in whom PTCA had been performed (PTCA-group). There were no deaths in the PTCA-group compared to 3 deaths (5.7%) in the control-group (ns). Two patients (3.8%) and three patients (5.7%), respectively, suffered an acute transmural myocardial infarction during the follow-up period (ns). Coronary artery bypass grafting (CABG) had been performed in five patients (9.4%) following PTCA, and in 17 patients (32.1%) of the control-group (p less than 0.002). The overall rate of serious cardiac events (death, myocardial infarction or CABG) amounted to 13.2% (seven patients) in the PTCA-group and to 43.4% (23 patients) in the control-group (p less than 0.002). Only in the PTCA-group was a repeat PTCA performed in 15 patients (28.3%) with restenosis (p less than 0.00003). 35 of 53 patients in the PTCA-group (66%) and 27 of 50 survivors in the control-group were free of symptoms at the end of follow-up (ns). These results demonstrate that PTCA in patients with single-vessel disease is followed by a marked reduction of serious cardiac events, predominantly of bypass-operations, but the necessity of a second PTCA-procedure in case of restenosis has to be considered. PMID- 1862668 TI - [The effect of hemodynamic changes in 24-hour milrinone infusion on sympathetic activity and the renin-angiotensin-aldosterone system in patients with severe heart failure]. AB - The hemodynamics of 18 patients (subgroup A) with severe heart failure (baseline Cl less than or equal to 1.55 l.min-1.m-2), including three patients with cardiogenic shock, and another 22 patients (subgroup B) with moderate heart failure (baseline Cl from 1.55 to 2.5 l.min-1.m-2) were investigated during a 24 h milrinone infusion, combined with investigation of the response of the sympathetic tone (plasma catecholamine levels) and the renin-angiotensin aldosterone system to the hemodynamic improvement in both subgroups. Cl increased (p less than or equal to 0.001) to 162.7% after 5 min and further to 206.4% of baseline after 30 min of milrinone therapy in subgroup A, and in B to 139.3% and further to 146.4% after 15 min. PCWP decreased (p less than or equal to 0.001) to 83.8% and further to 65.5% of baseline after 30 min in subgroup A, and to 58.4% in subgroup B. Heart rate decreased (p less than or equal to 0.05) from 99.4 to 94.7 bpm in A and showed a decreasing tendency in B. MAP rose in A from 75.5 to 79.4 after 1 h and further to 83.3 mm Hg (p less than or equal to 0.01) after 24 h; in subgroup B, MAP did not change. Plasma noradrenaline level decreased (p less than or equal to 0.001) in A from 1419.5 (B: 782.9) to 838.2 (B: 529.6) after 1 h and further to 655.1 (B: 467.9) pg/ml after 24 h. Plasma renin decreased (p less than or equal to 0.01) in A from 1047.6 (B: 460.2) to 597.4 (B: 222.5) and further to 392.6 (B: 191.7) microU/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1862670 TI - [Micrococcus luteus: a rare pathogen of valve prosthesis endocarditis]. AB - A rare case of prosthetic valve endocarditis caused by Micrococcus luteus is described and compared with the few cases reported in the literature, as well as the clinical features, microbiological profile, therapy, and prognosis of common prosthetic valve endocarditis. Micrococcus luteus is a constituent of the normal human buccal bacterial flora which forms yellowish colonies and appears as a gram positive coccus typically arranged in tetrades. Although of low virulence, the germ may become pathogenic in patients with impaired resistance, colonizing the surface of heart valves. In contrast to staphylococci (for which it may easily be mistaken) it is usually penicillin-sensitive. However, the most promising antibiotic regimen proposed for treatment of Micrococcus luteus seems to be a combination of vancomycin, amikacin, and rifampicin. If the infection leads to severe hemodynamic alterations, however, valve replacement may become necessary similar to the situation in prosthetic valve endocarditis caused by more aggressive and highly resistant bacteria. PMID- 1862671 TI - [Comment on the contribution: Schroder, T (1990), Immediate bypass operation prevents heart infarct in PTCA emergencies, Z Kardiol 79:669-676]. PMID- 1862672 TI - Surgical treatment of craniopharyngiomas. PMID- 1862673 TI - [Surgical significance of cavernous hemangioma of the brain stem]. AB - Cavernous hemangiomas are identified as source of brainstem hemorrhage in increasing numbers by magnetic resonance imaging. The optimal treatment of this rare vascular malformation, indication for surgery and time of intervention is still under discussion as the experience so far is mainly based on case reports. We have investigated a series of 20 patients with cavernous hemangiomas of the brainstem between 1986 and 1990, 10 of them underwent surgical removal of the lesion. Based on these experiences we conclude: Surgical removal of cavernous hemangiomas should be attempted in patients with recurrent hemorrhage, persistent or progressive neurological deficit. In cases with additional venous malformation the cavenoma should be selectively removed. Surgery should be radical, as residual cavernoma can cause recurrent bleedings. Surgery should be performed during the subacute stage. Late surgery increases the risk for additional neurological deficit. Neurophysiologic monitoring can be helpful to minimize surgical risk. PMID- 1862675 TI - Outcome and rehabilitation after aneurysmal subarachnoid haemorrhage. AB - 108 consecutive and unselected patients presenting with subarachnoid haemorrhage (SAH) due to cerebral aneurysm rupture were treated with a standardized regime. At 12 months after surgery 87 patients, who were available for review, were investigated with questionnaires, physical examination and neuropsychological tests. On the background of a comparatively low physical morbidity rate of 7% and mainly normal test results for concentration abilities, non-verbal memory function, word knowledge, logic and 3-dimensional thought, delay in rehabilitation was evidently caused by psychological problems. These were most manifest in increased anxiety, personality changes in form of depression or aggression, and lack of social contact and were exacerbated by apparently inadequate postoperative care. Therefore a psychologist should be involved during the first 12 months of rehabilitation, clinics should be held more frequently or access via phone to a neurosurgical information centre should be provided. The presented follow-up concept is suitable for assessing rehabilitation but for practical reasons should be shortened. PMID- 1862674 TI - Pontine hematoma. A report of three surgically treated cases. AB - Untreated pontine hematoma is always fatal, while surgical evacuation is effective and safe. After surgical intervention, immediate improvement and full or nearly full recovery may be observed. In this report, three successfully removed pontine hematomas are presented. The cause of this pathological entity, surgical interventions and their results are discussed and cases reported in the literature are reviewed. PMID- 1862676 TI - Assessment of cerebral perfusion in EC-IC bypass patients. PMID- 1862677 TI - ["How it all came about". On the beginnings of current neurosurgery in Germany up to the beginning of the "Zentralblatt fur Neurochirurgie"]. AB - Till the thirties of our century surgery of brain and spinal cord was done by general surgeons. At that time the activities of Ernst von Bergmann, Fedor Krause and the operative autodidact and Neurologist Otfried Foerster met with great response. These achievements, however, had no influence on the development and dissemination of Neurosurgery in Germany. The revolutionary work of Cushing concerning Neurosurgery had no effect on surgeons either. The results of the operative treatment of intracerebral tumors in Germany continued to be depressing. It's entirely the credit of Fritz Konig (Wurzburg) having caused the decisive change of this situation. He enabled his resident Wilhelm Tonnis to be educated by Herbert Olivecrona in his Department of Neurosurgery in Stockholm. After his return from Sweden the first independent Department of Neurosurgery was founded for Wilhelm Tonnis in Wurzburg. Wilhelm Tonnis tried to overcome the still existing opposition against the independence of Neurosurgery by the foundation of an own scientific journal. The "Zentralblatt fur Neurochirurgie" was founded in 1936 at the newspaper Publisher Ambrosius Barth, Leipzig. This "Zentralblatt fur Neurochirurgie" was the only scientific journal of the world till 1943. The consequences of war stopped its distribution abroad. This was the reason for the foundation of "The Journal of Neurosurgery" in 1944. Corresponding to its tradition the new beginning shall consolidate the scientific bond between all neurosurgeons of the world. PMID- 1862678 TI - [Ewing's sarcoma: literature review and presentation of 4 cases]. AB - Ewing's sarcoma occurs most often in young males of caucasian type and affects the medio-diaphysis of a long bone of the lower extremity, the pelvis and the humerus. Radiologically there is bone destruction, onion skin appearance, a Codman triangle and extension into the surrounding soft tissues. Microscopically, this tumor is composed of small round cells and it can be differentiated from non Hodgkin lymphoma, metastatic neuroblastoma and embryonal rhabdomyosarcoma. Recent immunological studies suspect a neuroectodermal origin. Ewing's sarcoma growths rapidly and spreads to lung and other bone locations. Without treatment, survival at 5 years is less than 5%. The actual therapeutic approach is multidisciplinary including surgery, chemotherapy and if necessary radiotherapy. With this approach actual survival rates at 5 years reaches 75%. PMID- 1862679 TI - [Sleeve resection for bronchial carcinoid tumors: results in 13 patients with an average follow-up of 6 years]. AB - In the period August 1974-April 1989 13 patients, 6 men and 7 women with a mean age of 36.9 years, underwent a sleeve resection for centrally located bronchial carcinoid tumours. Operations performed were: sleeve lobectomy of the right upper lobe 7; sleeve lobectomy of the left lower lobe 1; sleeve resection of the right main bronchus 2; sleeve resection of the left main bronchus 3. Five patients underwent preoperative laser therapy (from 1986 on). Histological diagnosis was typical carcinoid in all cases. Staging was T2N0M0 (stage I) in 7 patients and T3N0M0 (stage III A) in 6 patients. There was no perioperative mortality. During follow-up (mean 74.6 months) there was no late mortality and good results in 12 patients without signs of recurrence or bronchial stenosis. One patient underwent a completion pneumonectomy 16 months postoperatively because of anastomotic stricture without evidence of tumour recurrency. With centrally located bronchial carcinoid tumours sleeve resections are preferred to more extensive resections. The salvage of functional lung tissue in these generally young patients is important. The excellent short and long-term results substantiate this policy. PMID- 1862680 TI - Supraceliac aorta-to-femoral artery bypass: a case report. AB - The authors describe the technique of the supraceliac aorta-to-femoral artery bypass graft. This type of reconstruction is presented as a possible alternative in patients with relative contraindications to direct approach of the infrarenal abdominal aorta. PMID- 1862681 TI - [2 cases of duodenal duplication]. AB - Two cases of duodenal duplication are reported. It is a rare disease and is found commonly during infancy. Symptoms of partial duodenal obstruction are dominating the clinical picture. Upper gastrointestinal contrast radiography seems to be the best paraclinical examination. The surgical treatment is governed by the relationship of the cyst to the biliary and pancreatic ducts and the presence of ectopic gastric mucosa. If total resection of the cyst implicates a danger of injury to the common bile duct and the head of the pancreas and when one is tempted to perform a cystoenterostomy, the authors insist on the necessity to detect the presence of ectopic gastric mucosa by fluid pH determination and frozen section biopsy of the cyst wall. The presence of ectopic gastric mucosa requires a total resection of the cyst. PMID- 1862682 TI - [Cystic formations of the mesentery. Apropos a case report of a pseudocyst of the lesser omentum]. AB - Mesenteric cysts are rare intraabdominal tumors in surgical pathology. Their etiology has been subject to much discussion. Symptoms are variable and depend on specific complications. Localisation in the gastro-hepatic mesentery is uncommon and has been reported only in two previous issues. We describe a new case with literature review. PMID- 1862683 TI - Actinomycosis of the ano-rectum: a rare infectious disease mimicking carcinomatosis. AB - Abdominal actinomycosis is an infectious disease caused by Actinomyces israeli, a usual germ of the gastro intestinal tract. It gives unusual tumoral lesions with abcesses and fistulas. More rarely is abdominal actinomycosis at the end of the abdominal tube. Cope in 1949 said: "Actinomycosis occurs so seldom in the colon and the rectum that no surgeon, even if he be a proctologist is likely in a life time to see more than a few cases" (4). An anorectal actinomycosis case that looked like rectal cancer is reported. It was treated successfully by surgery and antibiotherapy. Some anatomopathologic and mainly histologic characteristics lead to the diagnosis. General and pathological aspects, symptoms, diagnosis, differential diagnosis and therapy of anorectal actinomycosis are discussed. PMID- 1862684 TI - Fatty acid binding to serum albumin in type I insulin-dependent diabetes mellitus. AB - Equilibria of binding of long-chain fatty acids to albumin in sera from type I diabetic patients and healthy adults were studied by dialysis exchange rate determinations and described by, p*, the reserve albumin concentration for binding of fatty acid, C*/p*, the total availability of fatty acids, where C* is the total concentration of non-esterified fatty acid, and L*, the fatty acid binding property of albumin, which is L* = p*/P + 0.05 C*/P, where P is the albumin concentration. Studies in samples from 81 diabetic patients and 99 healthy adults showed that availability of fatty acids increased with increasing fatty acid concentrations, equally in the two groups. Some diabetics had higher fatty acid concentrations, and thus higher fatty acid availabilities, than the normals. It is shown that the fatty acid binding property of serum albumin is individually variable, ranging about the same mean value in normal and diabetic persons but with a larger variation in the latter. The fatty acid binding property of albumin in serum, L*, and sixteen clinical parameters were measured in 42 of the 81 diabetic patients. Regression analysis indicated that L* was correlated to serum cholesterol concentration (probability of 0-hypothesis, p = 0.01) and to serum triglyceride concentration (p = 0.05). Values of L* were slightly correlated to age, age on diagnosis, duration, Body Mass Index (BMI), diastolic blood pressure, albumin excretion rate, serum creatinine concentration, and serum non-esterified fatty acid concentration with p-values varying from 0.10 to 0.50. For sex, retinopathy, hemoglobin A1c, systolic blood pressure, daily insulin dose, and blood glucose concentration no correlation to L* was found, p values ranging from 0.56 to 0.96. Non-enzymatic glycosylation of serum albumin did not decrease binding affinity for fatty acid in vitro. PMID- 1862685 TI - Diabetic autonomic neuropathy. AB - One of the earliest manifestations of diabetic neuropathy is denervation of the cardiovascular system; loss of heart rate variability may have a prevalence as high as 21.5% in diabetic patients, and declines at 1 beat/min/year, which is 3 times faster than in normal subjects. The cause of this neuropathy is unknown: attempts at decreasing the excess quantities of sorbitol, glucose and fructose in nerve tissue have lead to little functional improvement in man. Nerve ischaemia and immunological damage have stimulated increased interest lately, the latter particularly because of the structural homology of nerve growth factor and insulin. Symptoms from autonomic neuropathy are rare. When present they may well be intermittent, but never remit; they rarely progress or become disabling. One uncommon consequente of loss of sympathetic vascular tone is postural hypotension. This may result from failure of splanchnic vasoconstriction on standing. Food and insulin can greatly exacerbate the postural blood pressure fall. Reduced vascular tone in the neuropathic foot leads to increased arterio venous shunt flow. The local reflex control of this shunt flow is also abnormal: paradoxical vasoconstriction occurs in response to local skin heating and postural reflexes are reduced. This high shunt flow together with its abnormal vascular control may be important in the pathogenesis of neuroarthropathy and foot ulceration. The prognosis of patients with autonomic neuropathy is better than previously reported. Abnormal heart rate variability alone is of no prognostic value. The presence of symptoms, in particular postural hypotension, significantly reduces survival. The majority of deaths however, result from concurrent renal disease and macrovessel atheroma. PMID- 1862686 TI - Tryptophan content in serum and brain of long-term insulin-treated diabetic rats. AB - The metabolism of tryptophan (TRP) was studied in diabetic and insulin-treated diabetic rats throughout a five-month period. In alloxan diabetic rats the serum and brain TRP levels were decreased (serum: 38 to 48 mmol/l, brain: 8.6 to 9.2 mmol/g) in comparison to the values of control rats (serum: 59 to 64 mmol/l, brain: 11.3 to 12.6 mmol/g). Daily long-term (for 45, 75, 90 or 135 days) treatment with intermediately acting insulin (4 IU/rat, s.c.) was not able to restore brain concentration of TRP. On the contrary, the serum TRP concentrations were totally or partially restored. The concentrations of branched chain amino acids (BCAA) were increased in serum (valine = 361.2 to 461.0 mumol/l or leucine + isoleucine = 431.0 to 520.3 mumol/l) throughout the entire five-month examination period. Insulin treatment did not return serum concentration of BCAA to normal level in the observation period either. PMID- 1862687 TI - Determination of serum fructosamine from capillary blood samples. PMID- 1862689 TI - Association of hyperglycemia with dietary cyanogen and socio-economic level. The study of rural communities in south-east Nigeria. AB - An association of asymptomatic hyperglycemia with dietary cyanogens and socio economic level was ascertained in 2,000 volunteers in rural communities in South East Nigeria. The staples of the poor consisted of one or two bulky carbohydrate meals (derivatives of different species of cocoyam, cassava, yam and maize) eaten with vegetable soup in palm oil, melon seeds, snail, occasional meat and fish. The diet of the high income class included also beans, rice and more animal proteins. Alcohol (mainly palm wine) was consumed only occasionally. The subjects were divided into male and female and were age-matched into various age groups. Anthropometric data of each subject was obtained alongside the family history and socio-economic status. The subjects were further divided into low income vis-a vis high income groups. All the subjects were normal volunteers, ambulatory, asymptomatic and free from chronic or acute illness. The fasting capillary whole blood glucose (FBG) and 2-h blood glucose following a 75 g oral glucose tolerance test (OGTT) of each subject were measured. The body mass index (BMI) and dental caries scoring of each subject were also determined. The FBG levels and 2-h blood glucose following OGTT were significantly elevated in all subjects particularly in the low income groups except in the under 18-year group. The increases were observed in males and females although glucose levels were lower in the female age group. However, diagnosis of impaired glucose tolerance according to WHO criteria was present in both income groups. The BMI increased as the age increased particularly in the low income groups. There was a strong relationship between age, FBG, IGT and dental caries, respectively in the population. It is concluded that there was strong relationship between poverty, asymptomatic hyperglycemia, and impaired glucose tolerance in the area where cyanogen in diet was higher while there was marginal animal protein in the diet of the poor. PMID- 1862688 TI - Selective stimulation of insulin secretion by CCK-4 analogues having N-terminal modifications. AB - Synthetic analogues of CCK-4 in which Trp was replaced by D-Pro (peptide I), Thz (peptide II) and delta Pro (peptide III) have been studied for their insulin and glucagon releasing activities from the islets of Langerhans in vitro. Peptide I has been found to be the most potent insulin releaser among the three analogues and its activity is comparable to that of CCK-4. Unlike CCK-4, its three analogues (peptides I-III) do not stimulate the release of glucagon with basal concentration of glucose in the medium. However, with increasing glucose concentration, all the three analogues potentiate the glucose stimulus for insulin release. PMID- 1862690 TI - Urinary excretion of glycated albumin in insulin-dependent diabetic patients with normal urinary albumin excretion. AB - Glycation involves both circulating proteins, such as albumin, and structural proteins, such as the components of the glomerular basement membrane. A preferential excretion of glycated albumin (more anionic at physiological pH compared with unmodified plasma albumin) has been reported by some authors, but not by others. We therefore investigated the selectivity index (renal clearance of non-glycated albumin/clearance of glycated albumin) in 25 insulin-dependent diabetic patients with normal urinary albumin excretion and in 19 well-matched control subjects. The selectivity index was significantly higher in diabetic patients than in control subjects: 1.38 +/- 0.05 SEM vs 0.98 +/- 0.02, p less than 0.0001. This result is not consistent with a preferential urinary excretion of glycated albumin, at least in normoalbuminuric uncomplicated insulin-dependent diabetic patients. PMID- 1862691 TI - Insulin requirement of simple and complex carbohydrate foods in type 1 (insulin dependent) CSII-treated diabetic subjects, obtained by biostator. Correlation with glycaemic index. AB - The aim of this work was to observe whether different types of carbohydrates might require different insulin doses. Five type 1 CSII-treated diabetic subjects (age 39 +/- 4 years), C-peptide negative and in optimal metabolic control (HbA1c 7.5 +/- 0.2) were selected for the study. They were connected to the Biostator 6 times with an interval of 4-10 days between sessions and fed a meal containing 75 g of carbohydrates of different types: bread, pasta, potatoes, apples, oranges and sucrose. The following net (above basal) insulin requirement for the 30 meals were found (IU - mean + SD): bread 9.15 +/- 1.97; pasta 6.00 +/- 1.37; potatoes 7.05 +/- 2.58; apples 4.54 +/- 1.42; oranges 6.21 +/- 2.62; sucrose 7.83 +/- 2.33. A statistically significant difference was found by ANOVA among insulin requirements for foods (p less than 0.05). Single comparisons between bread and the other foods showed a statistically significant difference only between bread and apple (p less than 0.05). Mean coefficient of variation was 33.9% for the subjects and 30.7% for the meals. A significant correlation was found between Jenkins' glycaemic index and insulin requirement (r = 0.897; p less than 0.001). In conclusion, the high intraindividual variability of insulin requirement does not advice the use of the glycaemic index during optimized insulin therapy. PMID- 1862692 TI - Anthropometric studies in diabetes in the Tropics. AB - Anthropometric studies were carried out in three groups of diabetics seen in southern India, namely fibrocalculous pancreatic diabetes (FCPD) (n = 49) (a subtype of malnutrition related diabetes), insulin dependent diabetes mellitus (IDDM) (n = 55) and non-insulin dependent diabetes mellitus (NIDDM) (n = 104). Both FCPD and IDDM had significantly lower body mass index, skinfold thickness (triceps, biceps, subscapular and suprailiac), mid-arm circumference and fat mass compared to controls and NIDDM patients, (p less than 0.001 for all parameters). FCPD and IDDM males did not show any significant differences in any of the anthropometric parameters studied. Among the females, FCPD had lower triceps skinfold measurements (p = 0.007) and mid-arm circumferences (p less than 0.05) compared to IDDM patients. Patients with NIDDM did not show any significant difference compared to the control group. This study shows that both FCPD and IDDM patients have lower body mass and fat mass compared to NIDDM patients and control subjects. PMID- 1862693 TI - Plasma lipoproteins and apolipoproteins in insulin-dependent and young non insulin-dependent Arab women. AB - Plasma lipids, lipoproteins and apolipoproteins (apo) were analysed in 30 young Arab IDDM and 50 young insulin-requiring NIDDM women. The mean age of IDDM and NIDDM groups was 20.2 and 34.5 years, and mean duration of diabetes was 5.7 and 4.6 years, respectively. Two groups of 40 and 60 healthy women (matched for age and BMI) provided corresponding control groups. In comparison with control subjects, diabetics showed marked increases in the following parameters: total cholesterol (TC), low density lipoprotein (LDL) cholesterol, total triglycerides (TG), very low density lipoprotein (VLDL) triglycerides, phospholipids, apoB, LDL apoB, glucose and glycosylated hemoglobin (HbA1c) as well as the ratios of total cholesterol/high density lipoprotein (HDL) cholesterol, LDL-cholesterol/HDL cholesterol, LDL cholesterol/high density lipoprotein (HDL) cholesterol, LDL cholesterol/HDL-cholesterol, LDL cholesterol/high density lipoprotein 2 (HDL2) cholesterol and apoB/apoAI. Plasma LCAT activity, concentrations of HDL3 apoAI and apoAII in plasma and lipoprotein fractions were normal in both the diabetic groups. Levels of C-peptide, HDL, HDL2 and HDL3 cholesterol, plasma apoAI, HDL apoAI and HDL2 apoAI were markedly decreased in the diabetic groups as compared to their corresponding controls. There was no significant correlation between fasting glucose or HbA1c and any of the above parameters. Despite insulin therapy in both the diabetic groups studied, abnormalities in lipids, apoB and apoAI still persisted. Our data suggest a possible higher risk of atherosclerosis in these patients. PMID- 1862694 TI - The effects of bilio-jejunal diversion on streptozotocin diabetes in the rat. AB - Previous experimental indications that the internal biliary diversion (IBD), consisting in bilio-jejunal anastomosis, provokes an increase in glucose tolerance in healthy rats provide the basis for testing the hypothesis that this surgical procedure is capable of correcting pharmacologically-induced diabetes mellitus. To this object, the carbohydrate metabolism of an experimental group of six rats suffering from streptozotocin diabetes and treated with IBD (Lambert prosthetic choledoco-jejunostomy) was studied and compared with that of three control groups: normal, diabetic without surgery and diabetic with sham-surgery. Carbohydrate metabolism, assessed during 60-day period by means of specific tests (basal and fasting blood glucose and insulin, glucose tolerance and insulin sensitivity), demonstrated that the IBD provokes a definitive remission, either total or partial, of the artificial diabetes mellitus. The results lead to the hypothetical explanation that diversion of bile flow from the duodenum to the proximal jejunum activates the 'entero-insular axis', specifically by potentiating the B-cell stimulating effect of the so-called enteric hormone 'incretin'. PMID- 1862695 TI - Factors for development of secondary failure to sulfonylurea drugs in non-insulin dependent diabetes mellitus. AB - Thirty-five non-insulin-dependent diabetic subjects were divided into two groups, according to therapeutical approach. The first group consisted of 17 diabetics receiving sulfonylureas and maintaining a satisfactory metabolic control. The second group included 18 patients who were transferred from sulfonylureas to insulin treatment, i.e. patients developing secondary failure to sulfonylurea drugs. We established that the patients with secondary failure to sulfonylurea drugs show a significantly lower B-cell secretory response following stimulation with i.v. tolbutamide, a significantly lower peripheral insulin sensitivity by euglycemic hyperinsulinemic clamp, and an increased frequency of HLAB21 and HLADR1 antigens. This latter study was performed in 42 patients. We thus conclude that in these patients diabetes mellitus may be considered as a separate form of the disease, which needs reevaluation of the criteria concerning therapeutical approach, prognosis, and evolution. PMID- 1862696 TI - Serum lipids, microalbuminuria and metabolic control in diabetic children. AB - In order to analyse the role of long-term metabolic control on serum lipids of diabetic children, the authors studied 61 diabetics for a period of time of 18 months. The age of the patients ranged from 7.2 to 19.5 years; the patients were divided into two groups according to the presence of albumin excretion rate more than 15 micrograms/min: group A 46 children with albumin excretion rate less than 15 micrograms/min; group B 15 children with albumin excretion rate more than 15 micrograms/min. During the study, all the patients improved the quality of metabolic control but only in the diabetics of group A serum cholesterol and triglycerides levels fell significantly. The patients of group B did not modify their serum lipids concentrations in spite of the improvement of metabolic control. This study suggests that in the diabetic children with microalbuminuria it is difficult to normalize the lipid abnormalities by means of optimized insulin conventional therapy. PMID- 1862697 TI - [Recent parameters for diagnosis of challenging thyroid gland disorders: consequences for diagnosis and therapy]. AB - The recognition of the peripheral state of thyroid hormones is often disturbed by factors like pharmacological interferences or non-thyroidal illness, especially borderline hyperthyroidism may often be misjudged. Some serological parameters like the measurement of sex hormone binding globulin, precollagen-peptid I and III, osteocalcin, angiotensin converting enzyme and fibronectin are often elevated in such states and can indicate thyrotoxicosis of certain tissues. Such thyrotoxicosis-like alterations can be shown also in TSH-suppressive therapy with levothyroxine. In contrast to early publications there is obviously only a minor influence of levothyroxine treatment on bone metabolism, where a decrease of bone mass is less probable. Recent developments of sensitive and specific modifications in estimating antibodies against thyroidal peroxydase in recognizing thyroid autoimmune disease and of thyroglobulin in the follow-up of differentiated thyroid cancer are becoming important tools in clinical medicine. PMID- 1862699 TI - [Iodine containing drugs and thyroid gland function. A diagnostic and therapeutic problem]. AB - Iodine-induced thyroid dysfunction will become more important in Austria in the near future, because of the augmentation of the iodine content in salt in 1990. This review therefore tries to summarize the diagnostic and therapeutic problems that may arise in iodine-induced thyroid disease. After discussion of the physiologic reaction of the normal thyroid to iodine the most frequently used iodine-containing drugs used in Austria are presented. Special emphasis is laid on iodine containing antiseptics and on the antiarrhythmic drug amiodarone. The influence of iodine supplementation on the reaction of diseased thyroid glands to iodine overload is stressed. The diagnosis of iodine induced thyroid dysfunction is relatively simple, once it is thought of. Amiodarone-iodine induced thyroid disease may be an exception, because of the intrinsic effect of this drug on thyroid hormone metabolism. Since high intra-thyroidal iodine content inhibits the action of thyrostatics, therapy of iodine-induced hyperthyroidism may be complicated. Alternative possibilities such as cortisone, perchlorate or surgery in thyroid storm are presented. Substitution with 1-thyroxine in iodine-induced hypothyroidism may be harmful in elderly patients with cardiac problems. In conclusion, this review tries to present the state of the art of the solution of diagnostic and therapeutic problems in thyroid dysfunction due to iodine administration. PMID- 1862698 TI - [In vitro effects and possible clinical relevance of interleukin 3]. AB - Cytokines are mainly produced by monocytes and lymphocytes and influence a broad spectrum of physiological processes within the hematopoietic and the immune system. Clinical trials have mainly been initiated with a subgroup of cytokines namely the hematopoietic growth factors. Interleukin 3 (IL-3) was recently introduced into phase I and II trials. This factor was also termed "multipoietin" because of its ability to stimulate in vitro the hematopoietic stem cell and thus all three hematopoietic cell lines. The latest in vivo data, however, demonstrate that IL-3 stimulates leukopoiesis and megakaryopoieis with only marginal effects on erythropoiesis. In large clinical trials the therapeutic effect of this factor is investigated in patients with myelodysplastic syndromes. Further indications will be other primary bone marrow failures and aplasia caused by bone marrow transplantation, aggressive chemotherapy and radiation. Potential applications offered by combinations with other cytokines can hardly be foreseen. PMID- 1862700 TI - 1991--75th anniversary AARN. Our history--a proud heritage 1975-1979. PMID- 1862701 TI - Rheological properties of middle ear mucus in relation to goblet cell population in cat. AB - Seventeen mucoid middle ear effusions were collected from the tympanic cavity of 15 cats 1 or 2 weeks after tubal obstruction. Middle ear mucosa was also taken both from the tympanic cavity and bulla, and the number of goblet cells was counted. Both elasticity (G') viscosity (eta') of the mucoid effusion were determined with an oscillating sphere magnetic rheometer and compared with goblet cell count. There was a significant correlation between G' and goblet cell population in the tympanic cavity. A similar significant correlation was observed between eta' and goblet cells. The G' and eta' values of the mucoid mucus were much higher than the optimal viscoelasticity for mucociliary transport. Results indicate that the mucus obtained in this study mainly originated from the goblet cells, and that its viscoelasticity was beyond ideal values for mucociliary transport. PMID- 1862702 TI - Rheological and biochemical properties of middle ear effusions from experimental otitis media in cats. AB - Both rheological and biochemical analyses were performed on middle ear effusions (MEEs) from cats with experimental otitis media with effusions (OME) induced by obstruction of the Eustachian tube. This study was undertaken in order to clarify the factors determining rheological properties (elasticity and viscosity) of MEEs. The viscoelasticity of the effusions had a positive significant correlation to fucose/total protein concentration (TPC), and a negative correlation to cathepsin B level/TPC. No correlation was observed between albumin level/TPC and viscoelasticity. These results indicate that in cats the rheological properties of MEEs depend on the level of secretory glycoproteins in MEEs and on the severity of inflammation in the early stage after tubal obstruction. PMID- 1862703 TI - The relationship between proteases activity and glycoprotein levels in middle ear effusions from experimental otitis media in cats. AB - The relationship between lysosomal proteases activity (elastase and cathepsin B) and levels of mucous glycoproteins in middle ear effusions (MEEs) was studied using a cat model of otitis media with effusion (OME) induced by Eustachian tube obstruction (ETO). The ratio of cathepsin B activity to total protein concentration (TPC) in MEE was 25.6 +/- 19.4 RFU/g x dl-1 at 1 week after ETO, and increased with the duration of OME. The ratio of elastase activity to TPC had a significant correlation to total leukocyte count. The ratio of fucose levels to TPC, which is one of the parameters reflecting levels of mucous glycoprotein, at 1 week after ETO was significantly higher than that at both 2 and 4 weeks after ETO. The percentage of glycoprotein levels absorbed to wheat germ lectin was highest at 1 week after ETO, and decreased with the duration of OME. In conclusion, mucous glycoproteins in cat occupy a larger portion of glycoproteins in MEE at the early stage of OME, and elastase and other lysosomal proteases may play a role in both stimulation of mucin release from goblet cells and mucin degradation. The balance of these processes seems to be a key factor determining mucin levels in MEEs. PMID- 1862704 TI - Effects of endotoxin and neutrophil lysate on experimental otitis media with effusion in cats. AB - Middle ear effusion (MEE) from otitis media with effusion (OME) contains large amounts of chemical mediators and substances from bacteria, which may act on the mucosa itself and cause further changes in the inflamed mucosa and MEE. To clarify the effects of such substances in MEE, we instilled endotoxin (LPS) or allogeneic neutrophil lysate (NL) into the middle ear cavity of OME induced by Eustachian tube obstruction (ETO). ETO + LPS and ETO + NL groups showed retention of a large amount of MEE as a characteristic difference between ETO alone group and these groups. The instillation of LPS into the middle ear cavity of the ETO model significantly increased the number of total cells and the ratio of the concentrations of albumin to total protein in MEEs. The instillation of NL significantly increased the number of goblet cells in the middle ear. These facts indicate that the pathology of OME may change in response to various factors added to MEE. Hence, we propose that a vicious circle of self-mediated inflammation is a possible causative factor for chronic OME. PMID- 1862705 TI - A quantitative study of the ciliary area of experimental otitis media with effusion in cats. AB - A quantitative electron microscopic study was performed to determine the extent of the ciliary surface area of the middle ear epithelium in cats. In normal cats, 97.8% of the middle ear mucosa in the hypotympanum and 45.9% in the upper part of the bulla were covered by cilia. Eustachian tube obstruction (ETO) significantly reduced the ciliary area to 73.1% in the hypotympanum and to 16.2% in the upper part of bulla at 1 week after ETO. Instillation of Escherichia coli lipopolysaccharide (LPS) or cat polymorphonuclear leukocyte (PMN) lysate into the middle ear cavity followed by ETO did not reduce the ciliary area, compared with ETO induced alone. Our results indicate that ETO reduces the ciliary area of the middle ear mucosa and that LPS or neutrophils do not enhance reduction of the ciliary area compared to ETO induced alone in this experimental condition. PMID- 1862708 TI - A light and electron microscopical study of membranocystic lesions in a case of lupus erythematosus profundus. AB - A light and electron microscopical study on membranocystic lesions (MCL) in a case of lupus erythematosus profundus (LEP) is reported. The patient was a 16 year-old female who presented with subcutaneous nodules on both upper arms. The light microscopic features were consistent with LEP, and the result of an immunofluorescence band test supported this diagnosis. A peculiar finding in this case was MCL in the subcutaneous tissue. Ultrastructurally, these were thin membranes without a tubular structure and tortuous thick membranes composed of minute tubules. The lesions were very similar to the fatty tissue changes in membranous lipodystrophy. On the other hand, the basement membranes of the blood vessels were thickened and multilayered, and the lumina were narrowed by endothelial swelling and thickening of the vessel wall. Our findings suggest that the MCL in LEP result from circulatory disturbance of the fat tissue. PMID- 1862707 TI - Paired twisted filaments in human pinealocytes. AB - Paired twisted filaments (PTF) have been confirmed and described ultrastructurally in the normal human pineal gland for the first time. The PTF showed a peculiar double helical structure, measuring 12 to 25 nm in maximal helix width with a half-periodicity of 30 to 35 nm (periodicity of the constrictions). Each filament was about 10 nm wide. The PTF formed parallel aggregates in the perikaryotic cytoplasm of the pinealocytes. In 8 of 12 autopsied middle-aged to elderly individuals, the PTF were present in a small proportion of pinealocytes. The identity of the PTF remains unclear in terms of their apparent similarity to the paired helical filaments observed previously in aged rats. However, the age distribution of individuals with PTF suggests that the intermediate filaments of human pinealocytes are more susceptible to early deterioration during aging than those of other cerebral neurons. PMID- 1862706 TI - Detection of burst-promoting activity in spleens of myeloproliferative sarcoma virus-infected mice using serum-free cultures. AB - Myeloproliferative syndrome was induced in adult DBA/2 mice by inoculation with myeloproliferative sarcoma virus (MPSV) and Friend murine leukemia virus (F-MuLV) as a helper virus. On day 26 after infection, the spleen weighed a maximum of 2.0 g (about 30 times the control weight). Assay of multipotent stem cells in vitro showed that the more enlarged spleens contained an increased number and concentration of mixed colony-forming units (CFU-mix) (at maximum, 11 times higher than the control). When the supernatant of cultured spleen cells was added to a serum-free bone marrow cell culture with or without erythropoietin (Epo) for detection of burst-promoting activity (BPA), it enhanced erythroid mixed colony (E-mix) formation only in the presence of Epo (p less than 0.05). Even when addition of Epo was delayed, it still induced a significant number of E-mix (p less than 0.05). These findings rule out a mimic effect of Epo resembling BPA and indicate the presence of BPA in the spleen. The culture supernatant also supported the proliferation of interleukin 3 (IL-3)-dependent 32Dcl cells. Therefore, although purification of the BPA substance has not yet been accomplished, BPA in the supernatant seems to depend on the presence of IL-3, which is known to be one of the factors stimulating multipotent hemopoietic stem cells. The presence of BPA- or CFU-mix-stimulating activity in the spleen after infection might be responsible for the development of panmyelosis, which is a characteristic of MPSV-induced myeloproliferative syndrome. PMID- 1862709 TI - Paraganglioma of the cauda equina. A case report and review of the literature. AB - A case of paraganglioma of the cauda equina is reported. The patient was a 55 year-old Japanese woman who complained of lower back pain and gradual weakening of the left lower extremity, she was diagnosed as having a spinal cord tumor, and the tumor was removed surgically. Histologically, the tumor was encapsulated, and consisted of solid nests of large, polyhedral epithelioid cells with abundant eosinophilic cytoplasm. The nests were separated from each other by a thin fibrovascular stroma. Grimelius staining revealed neurosecretory granules in the cytoplasm of the tumor cells. This was further confirmed by electron microscopic observation. The tumor cells were immunohistochemically positive for neuron specific enolase (NSE), but negative for glial fibrillary acidic protein (GFAP). On the basis of the histologic, immunohistochemical and electron microscopic features of the tumor cells, the tumor was diagnosed as paraganglioma. The cauda equina is a rare location for this type of tumor, and only a limited number of cases have been reported. PMID- 1862710 TI - Primary osteosarcoma of the ovary. A case report. AB - A case of primary osteosarcoma arising in the left ovary of a 75-year-old female is described. The chief complaint was a sensation of lower abdominal mass. An abdominal plain film showed a large calcified mass in pelvic region, and a preoperative diagnosis of "ovarian fibroma" was made. The excised tumor was divided into 4 pieces, resembling an oyster shell. Microscopically, the tumor fragments were composed of compact bone or woven bone with surrounding atypical osteoblasts and osteoclasts. The tumor was partly composed of numerous spindle cells with malignant osteoid or atypical chondroid formation, and diagnosed as "osteosarcoma". The cystic part of the lesion was lined with a single layer of columnar cells, but the tumor contained no other germ elements or stem cells, or malignant epithelium. Therefore, it is doubtful that this tumor originated from teratoma or malignant mixed mesodermal tumor, and we conclude that this ovarian osteosarcoma arose through a neoplastic change in ovarian stromal cells. The patient died 4 months after surgery due to intra-abdominal and intrathoracic dissemination of the tumor. PMID- 1862711 TI - [Bioethics and mental health: reflections for Latin Americans]. PMID- 1862712 TI - [Epidemiologic bases of mental health programs for violent behavior]. AB - This article reviews the "case for action" for mental health programs on violent behavior. Mortality statistics for the region of the Americas show that the potential years of life lost due to violent behavior-related causes of death are of higher magnitude than those due to malignancies and intestinal infections. The impact of deaths associated to violent behavior is discussed from the perspective of the grief process and the post-traumatic reactions in the survivors. The possible role of mental health professionals in the prevention of some types of violent behavior and its consequences is indicated. PMID- 1862714 TI - [Conflict resolution: a new perspective]. AB - The field of conflict resolution has been focusing on certain implicit postulates related to the nature of three central concepts, namely: communication, conflict, and change. The present paper "undermines" so to speak, these three concepts by demonstrating the positivistic basis the field of conflict resolution features, even though recent contributions challenge such basis. A poststructural perspective on communication, conflict, and change is proposed as an alternative able to generate new tools and techniques for research as well as intervention in conflicts. PMID- 1862715 TI - [Review of the concept of personality deterioration in schizophrenia]. AB - Thirty-two patients suffering from schizophrenia (according to DSM-III, and chronic evolution characteristics, have been studied for 10 years. All of them presented signs of schizophrenic deterioration. They had been institutionalized for five years at least, with no leave at all. Some trends of psychiatry highlighting schizophrenic deterioration as an irreversible residual phenomenon are referred to as well as the biological studies relating causitively deterioration to atrophic alterations of the brain. During research, combined features from both therapeutic, and rehabilitation techniques were administered to the population under study, namely: Individual Psychotherapy, Family Psychotherapy, Occupational Therapy, and biological treatments. Nine patients presented a paranoidical form of schizophrenia; 6, a disorganized form; 4, an indifferenciated form; 5, a residual form, and 5, a catatonic form. Close to the end of research, 22 patients were given their discharge certificate after recovery; two were discharged but came back to hospital for short admissions; four are still institutionalized with no improvement foreseen; two are still institutionalized, however at a rehabilitation stage. Finally, two patients passed away during research. It is the author's contention that these results show a symptomatic variability determining that 70% of cases considered as clinical observations are intended to be construed as a dynamic phenomenon--and not as a static-crystallized one. PMID- 1862713 TI - [Biomedicine and quality of life: a theoretical analysis]. AB - The notions of illness (subjective feeling), disease (technical labelling), and sickness (social evaluation) are used for highlighting the fact that they constitute semantic spaces which may not coincide. Several factors explain the predominance of biomedical thinking, which must be construed as a cultural system in order to permit an appraisal of its values and weaknesses in relation to other systems such as popular, and folk systems. Quality of life as a research area emphasizes the illness side of the health care system, and may be defined as a tension between expectations and results. It is pointed out that a sound health care system should strive for a comprehensive multidimensionality integrating technical, personal, and social points of view. PMID- 1862717 TI - [Immunological aspects of psychotic patients]. AB - In one study on patients with thyroideopathies at Hospital Escuela, Tegucigalpa, Honduras, four patients were found with psychosis, and high values of antimicrosomal, and antithyroid globulin antibodies. In one control study, the presence of ATA is associated to a high incidence of family antecedents of immunological disease, thyroids, and mental diseases--especially schizophrenia. PMID- 1862716 TI - [Therapeutic approach to adolescent drug addicts]. AB - Changes that the adolescent psychical structure undergoes--due to the very vicissitudes of this development stage--tend to promote, and favor acting out mechanisms (i.e. an alloplastic coping of conflicts), as a homeostatic resource. Hence, the risk for youths to abuse drugs as an internal equilibrium element is higher at that stage than it should be expected in adulthood. Owing to the complexity of such a phenomenon, it is suggested than both the understanding of the situation at stake as well as the therapeutic intervention among adolescents with drug abuse problems should focus on the multidisciplinary side. Three basic therapeutic approaches for the treatment of drug abusing adolescents--namely psychodynamic, medical, and psychosocial perspectives, respectively--are briefly commented, and illustrated with clinical vignettes. PMID- 1862718 TI - [Community intervention during economic disasters]. AB - A political conflict forced banks to close down in Panama during March 1988. Thus, thousand of families were unable to meet their most basic needs during that lapse of time. This paper describes a community intervention program that was set up in the midst of such an economic disaster. That program emphasized mental health consultation techniques to help devising an effective organizational action as well as developing standards to determine needs, and a clear-cut two way communication with the affected families. The incidence of emotional disorder was assessed with the Self Report Questionnaire, and crisis intervention was offered to any people who should apply for it. Cognitive responses, coping behaviors, and social supports were also assessed. Results showed that those individuals excluded from a full participation in their culture were much more likely to develop emotional disorders. Finding that affected people showed a scarce self-help behavior was interpreted as a feature of the transcultural transaction between affected people, and professionals. PMID- 1862719 TI - [Acute and subacute catatonic syndromes with weight loss. Its favorable development with electroconvulsive therapy]. AB - When following a malignant course, acute, sub-acute catatonias generally tend to cause bed-sores, loss of weight, and, within a few months, cachexia, ematiation, and marasmus. In general, they develop a periodical character provided they are adequately treated. What is more noteworthy in cachectic catatonias is a favorable reaction to electro convulsive therapy (ECT) which may be thus considered a principal indication for treatment. This paper presents the case of four catatonic patients with severe loss of weight, that remarkably improved with ECT. PMID- 1862721 TI - [Psychometrics of aggressiveness]. PMID- 1862720 TI - [Marginal or cycloid psychoses and the Bender test]. PMID- 1862722 TI - [A case of demonic possession in Chile in the XIX century: its implications for the development of the Chilean psychiatry]. PMID- 1862723 TI - Mental rotation in perspective problems. AB - The present paper demonstrates that mental rotation as used in the processing of disoriented objects (Cooper and Shepard 1973) can also be used as an explanatory concept for the processing of perspective problems in which the task is to imagine how an environment will appear from another vantage point. In a cognitive map, subjects imagined an initial line of vision and subsequently processed a reorientation stimulus, requesting them to imagine a turn over 0, 45, 90, 135, or 180 degrees. Time for a reorientation increased linearly with the size of the imaginary turn up to 135 degrees and decreased for turns of 180 degrees; apparently, about-faces were relatively easy to imagine. The increment of reorientation time between 0 and 135 degrees was larger for maps presented in unfamiliar orientations such as South-West up. Both the increment and the interaction with familiarity are consistent with an explanation in terms of mental rotation. PMID- 1862724 TI - Multi-stepping saccadic sequences in humans. AB - A number of paradigms are reported in which multi-stepping saccadic sequences (MSS) are reliably elicited in normal subjects. It was observed that MSS are consistently associated with a prolongation of the initial saccade latency. Further experiments show that this phenomenon is validated across a number of independent eye movement tasks. However, the probability of MSS occurring is reduced when temporal constraints are imposed on the latency of the response. An interpretation of these task-elicited MSS in terms of the neural mechanisms controlling voluntary saccades is proposed. PMID- 1862725 TI - Categorization and identification of simultaneous targets. AB - Early and late selection theories of visual attention disagree about whether identification occurs before or after selection. Studies showing the category effect, i.e., the time to detect a letter is hardly affected by the number of digits present in the display, are taken as evidence for late selection theories since these studies suggest parallel identification of all items in the display. As an extension of previous studies, in the present study two categorically different targets were presented simultaneously among a variable number of nontargets. Subjects were shown brief displays of two target letters among either 2, 4 or 6 nontarget digits. Subjects responded 'same' when the two letters were identical and 'different' otherwise. Since the 'same-different' response reflects the combined outcome of the simultaneous targets, late-selection theory predicts that the time to match the target letters is independent of the number of nontarget digits. Alternatively, early-selection theory predicts a linear increase of reaction time with display size since the presence of more than one target disrupts parallel preattentive processing, leading to a serial search through all items in the display. The results provide evidence for the early selection view since reaction time increased linearly with the number of categorically different nontargets. A control experiment revealed that none of the alternative explanations could account for the display size effect. PMID- 1862727 TI - Concurrent verbal interference of right and left proximal and distal upper extremity tapping. AB - The purpose of this study was to investigate crossed and uncrossed control of the proximal (upper arm and shoulder) and distal (lower arm and hand) musculature of the arms using the dual-task paradigm. Forty-one strongly right-handed men performed a tapping task using primarily the musculature of the upper or lower arms, with and without concurrent verbal processing demands. The results showed that the left distal region was distinguished from the other three effector locations by its relative insensitivity to the demands of the dual-task (verbal processing) condition. Rapid alternating movements of the left arm were functionally independent from the left index finger location in response to dual task demands. Dual verbal and tapping demands at this effector produced greater interference on both the primary and secondary task. The results preclude the attribution of interference effects to manual dominance factors alone. The results generally support anatomical accounts of increased ipsilateral control over left side arm but not hand movements. Neither the traditional cognitive hemispheric model nor the manual dominance hypothesis were adequate in accounting for the results. An alternative generalized capacity hypothesis was required to account for performance at the LE. PMID- 1862726 TI - Target--distractor separation and feature integration in visual attention to letters. AB - The interference produced by distractor letters diminishes with increasing distance from a target letter, as if the distractors fall outside an attentional spotlight focussed on the target (Eriksen and Eriksen 1974). We examine Hagenaar and Van der Heijden's (1986) claim that this distance effect is an acuity artefact. Feature integration theory (Treisman 1986) predicts that even when acuity is controlled for, distance effects should be found when interference is produced by conjoined distractor features (e.g. letter-identities), but not when interference arises from isolated distractor features (e.g. letter-strokes). The opposite pattern of results is found. A model is proposed in which both letter strokes and letter-identities are derived in parallel. The location of letter strokes can also be coded in parallel, but locating letter-identities may require the operation of attention. PMID- 1862728 TI - Hemispheric processing of global form, local form, and texture. AB - Hemispheric processing of global form, local form, and texture of hierarchical patterns composed of many, relatively small elements and patterns composed of few, relatively large elements was examined in two experiments, employing a Stroop-type paradigm. In experiment 1 subjects were instructed to attend either to the global or the local level of the pattern and to identify the form at the designated level. In experiment 2 subjects were to identify the global form or the texture. A right visual field (left hemisphere) advantage was obtained for detection of local form, and a left visual field (right hemisphere) advantage was obtained for detection of global form. When many-element patterns were processed in terms of global form and texture, the results failed to show reliable hemispheric differences. The results suggest that the hemispheres differ in their sensitivity to the relatively more global versus the relatively more local aspects of visual patterns which require focused attention (as in global/local form detection). When the task involved distributed attention (as in texture detection) no lateralized effects were observed. PMID- 1862729 TI - Peripheral visual changes and spatial attention. AB - Three experiments are reported investigating the attentional effects of peripheral visual changes. In agreement with previous work, experiment 1 demonstrated facilitatory and inhibitory effects of a peripheral visual change on the latency of peripheral target detection. However, after a few minutes practice the facilitatory effect disappeared entirely. The inhibitory effect, though slightly reduced in later blocks, remained significant. Hence, the two effects are dissociable and not inter-dependent as argued by Maylor (1985). In experiments 2 and 3 the perceptual salience of the peripheral cue was manipulated. With a low energy, barely noticeable cue there was no reduction in either facilitation or inhibition as a function of practice. In contrast, the attentional effects of cues higher in energy tended to diminish with practice. Theoretical implications of these data are discussed. PMID- 1862730 TI - Efficacy and safety of alprazolam, imipramine and placebo in treating panic disorder. A Scandinavian multicenter study. AB - As part of the cross-national collaborative panic study, a double-blind comparison of alprazolam, imipramine and placebo was performed in Scandinavian outpatients with panic disorder according to DSM-III; 41 patients were randomly allocated to each drug. Doses were increased for 3 weeks to an average of about 6 mg alprazolam, 150 mg imipramine and a corresponding number of placebo capsules, which were then given for 5 weeks. No more than supportive psychotherapy was given. Key symptoms were rated weekly. The drugs were tapered for 4 or 8 weeks and the patients were followed up for 6 months. Compliance at 3 weeks was 95% for alprazolam, 83% for imipramine and 88% for placebo; at 8 weeks 95% for alprazolam, 73% for imipramine and 46% for placebo. At 3 weeks plasma determination showed that the proportion taking diazepam outside the protocol was 0% for alprazolam, 19% for imipramine and 31% for placebo; at 8 weeks the corresponding proportions were 3%, 11% and 16%. Intention-to-treat analysis showed that freedom from panic attacks was obtained for 68% with alprazolam, 61% with imipramine and 34% with placebo. Alprazolam was more effective than imipramine and placebo on anticipatory anxiety and phobic symptoms. Globally rated by physicians and patients, about 60% had complete remission with alprazolam and imipramine and 30% on placebo. At least partial remission was obtained in about 85% with alprazolam, 70% with imipramine and 40% with placebo. Alprazolam had a more rapid onset of action than imipramine on all symptoms. Side effects were generally mild, with a preponderance of drowsiness for alprazolam and anticholinergic effects for imipramine. Tapering was uneventful without significant discontinuation phenomena. During taper and follow-up, several patients in remission relapsed, leaving approximately 30% patients in complete remission in all groups. To obtain more stable improvement, either long-term drug treatment or combinations of drug treatment and psychotherapy should be evaluated. PMID- 1862731 TI - A trend analysis of changes during treatment of panic disorder with alprazolam and imipramine. AB - A total of 123 Scandinavian patients participated in a cross-national study of panic disorder. Twelve outcome measures, including number of panic attacks and phobias, have been used to describe changes in symptoms during treatment. This article gives a trend analysis of remission for each variable, analysing changes through the total period from baseline to week 8 and also changes in first and second half of this period, separately. Important differences between treatments are demonstrated. Alprazolam had an early effect on variables relating to panic attacks, such as severity of spontaneous attacks and avoidance, whereas imipramine showed a more delayed effect on global measures. Duration of illness, sex and the occurrence of depression in patients' history all affected the sequence of improvement. PMID- 1862732 TI - Characteristics of panic disorder patients responding to placebo. AB - Forty-one panic disorder patients receiving placebo were investigated in a double blind comparison of alprazolam, imipramine and placebo in panic disorder. A significantly higher drop-out rate was found in the placebo group than in the active treatment groups, but placebo response was found in 34% of the patients, defined as reduction of panic attacks to zero, and in 23%, defined as a score of greater than or equal to 8 on the Physician Global Improvement Scale (0-10 points). Several predictors of response to placebo were found. The responders had fewer panic attacks than the nonresponders at baseline. They also reported less psychopathology and were less help-seeking than the nonresponders. The implications for psychopathology and possible response to psychotherapy among responders and nonresponders are discussed. It is hypothesized that the responders show more signs of realistic processing of internal and external stimuli and fewer signs of subjective distress than the nonresponders. Responders will therefore probably be more responsive to psychotherapy than nonresponders. PMID- 1862733 TI - Secondary depression in panic disorder: an indicator of severity with a weak effect on outcome in alprazolam and imipramine treatment. AB - Depressive symptoms are frequent in panic disorder. Among 123 Scandinavian patients participating in a placebo-controlled multicenter study of the efficacy of alprazolam and imipramine treatment in panic disorder, 21% and 23% fulfilled the DSM-III criteria of current and past major depressive episode, respectively, and 17% had dysthymia, even when melancholia and depressive episode with onset prior to the panic symptoms were excluded. According to a subscale of the Hamilton Rating Scale for Depression (HRSD) with higher validity than the full scale, 18% were classified as major depression and 57% as minor depression. A major finding was that patients with affective symptoms had higher scores on many psychopathological measures, including several Symptom Checklist-90 factors. Accordingly, secondary depression was suggested as an indicator of the severity of panic disorder. Depressed and nondepressed patients significantly improved on major outcome measures, but patients with current minor or major depression improved less. Although the sample was too small for detailed analysis of differences in drug efficacy, there was no indication that imipramine was more effective than alprazolam, considering scores on an HRSD subscale. PMID- 1862734 TI - Alprazolam, imipramine and placebo treatment of panic disorder: predicting therapeutic response. AB - Factors that predicted the outcome of drug treatment (alprazolam or imipramine) of panic disorder were studied in a sample of 123 Scandinavian patients participating in a multicenter placebo-controlled 8-week trial. The attrition rate was 95% for alprazolam, 73% for imipramine and 46% for placebo. For the intention-to-treat and 3-week-completer samples, drugs and anxiety symptoms at baseline were the best predictors of improvement on the Global Improvement Scale and on symptom scales focusing on panic attacks, phobic behavior and anticipatory anxiety. For completers of the 8-week trial, only baseline scores predicted outcome. Generally, more severe symptoms at baseline predicted a worse outcome. A subsample of patients had a marked placebo response. Avoidance, sex, age, childhood psychopathology and previous treatment experience had no or only a weak impact on the outcome. The relationship between panic disorder and mood disorder is presented elsewhere. PMID- 1862735 TI - Validation criteria for panic disorder as a nosological entity. AB - Panic disorder (DSM-III, DSM-III-R) has been thoroughly studied in recent years. The main evidence for panic disorder as a nosological entity is reviewed, to delineate some important questions for future research. Validation criteria include epidemiological, phenomenological, genetic, neurobiological, pharmacological and behavioral findings. Biological, behavioral and psychodynamic considerations on etiology, pathogenesis and treatment are presented. PMID- 1862736 TI - New York Academy pulmonary meeting--March 22, 1990. PMID- 1862737 TI - In vitro influence of ketoprofen on the proteoglycan metabolism of human normal and osteoarthritis cartilage. AB - We investigated the influences of ketoprofen on the proteoglycan (PG) turnover of human articular cartilage explants in three groups: normal young with a high basal PG synthesis, normal adult and osteoarthritis cartilage, both with a low basal PG synthesis. Ketoprofen had no influence on the mean PG synthesis rate of normal adult and OA cartilage after 4 days of culture nor on the cartilage PG content after 8 days of culture. There was no relation between the histological grade of OA and effects of ketoprofen. In normal young cartilage ketoprofen induced an increase of the PG synthesis rate when added to the culture in a concentration of 10(-4) M. No correlation existed between the effect of ketoprofen and the basal PG synthesis of normal cartilage. PMID- 1862738 TI - The anti-inflammatory activity of a low molecular weight component derived from the milk of hyperimmunized cows. AB - "Immune" milk has been utilized as a source of biologically active compounds for many years. In the present study, a low molecular weight fraction, isolated from the milk of dairy cows hyperimmunized with a multivalent bacterial vaccine (HIMF), has been evaluated for anti-inflammatory activity. Analysis was carried out using the rat hind-paw oedema assay. HIMF was shown to have a marked anti inflammatory effect in this model and carrageenin-induced oedema was suppressed by up to 80% in individual experiments. The agent was active following oral, subcutaneous, intramuscular, intraperitoneal or intravenous administration. Intravenous injection was particularly effective and amounts as small as 1 mg significantly reduced the inflammatory response to carrageenin. The experiments have established that milk from hyperimmunized cows contains a highly active anti inflammatory compound and form a basis for further studies, which will attempt to isolate and further characterize the active moiety. PMID- 1862739 TI - Modulation of exudate inflammation parameters in rat carrageenan-induced granuloma by modification of exudate iron levels. AB - We have used the carrageenan-induced pouch-granuloma in rats to investigate how changes in low-molecular-mass iron chelate levels in the exudate, induced by iron loading (iron-dextran) or chelation (desferrioxamine) influence cellular and systemic inflammatory parameters. In the iron-treated group we observed a rapid decrease in the number of leukocytes and exudate volume; there was also an increase in ferritin iron and low-molecular-mass iron chelates, and on the eighth day a systemic response. In the desferrioxamine-treated group we detected a decrease in low-molecular-mass iron chelates, ferritin iron, and an increase in the number of leukocytes. We describe the protective effects of desferrioxamine against the deleterious effects of ferrous iron and relate this to its chelating and scavenging activity. The results suggest that the levels of low-molecular mass iron chelates modulate the inflammatory response, possibly through their contribution to the oxygen free radical generation, which is responsible for the cell membrane damage and subsequently its death. The modulatory action of iron dextran and desferrioxamine support our hypothesis. PMID- 1862740 TI - Body temperature modulates the effect of platelet-activating factor (PAF) on airways responsiveness in the rabbit. AB - Platelet-activating factor (PAF) is a potent mediator known to cause bronchoconstriction and increase airways responsiveness. In vitro studies have shown that the effects of PAF on cell function can be very temperature-dependent. The aim of the current study was to investigate the effect of elevated body temperature on numbers of circulating cells and pulmonary function in anesthetized rabbits in response to PAF. PAF was given intravenously, at a dose of 1.2 micrograms/kg hour, whereas the control experiments were performed after the animals received a saline infusion. Alteration of airways function was assessed by measuring specific pulmonary conductance (SGL) and dose-response relationships to inhaled histamine, where airways responsiveness was expressed as the effective concentration causing 50% of maximal change in specific airways conductance (EC50SGL). The rabbits were studied at two body temperatures: a normal temperature (rectal temperature of 39.8 C), and a higher temperature (rectal temperature 41.2 degrees C). Changes in circulating inflammatory cells, plasma corticosterone concentrations and in hematocrit were also monitored, to examine some potential mechanisms which might explain why body temperature altered airways responsiveness. At the normal body temperature infusion of PAF caused a significant increase in airways responsiveness (p less than 0.025), while at the high body temperature, there was a significant decrease in responsiveness (p less than 0.025). However, at both body temperatures, a profound but similar thrombocytopenia and neutropenia was observed. While plasma corticosterone levels and hematocrit showed increases coincident with the infusion of PAF, this response was unchanged by altering body temperature. We conclude that increased body temperature reduces the effect of PAF on airways responsiveness apparently through a mechanism independent of PAF effects on hemoconcentration, plasma corticosterone or circulating inflammatory cells. PMID- 1862741 TI - Comparative effects of two potentiating peptides (KPP and BPP9a) on kinin-induced rat paw edema. AB - We have previously shown that KPP, a kinin potentiating peptide generated by tryptic digestion of human plasma proteins potentiated kinin effects on isolated smooth muscle preparations like guinea-pig ileum with high potency and specificity. We also obtained evidence suggesting that, unlike other potentiating peptides, KPP exerts its effect by a mechanism different from the inhibition of kinin metabolism by angiotensin converting enzyme, neutral endopeptidase and kininase I. Here we show the potentiating effect of KPP and of BPP9a, a potentiator derived from snake venom, towards the rat paw edema induced by bradykinin (BK). Our results show that: a) KPP is 25-fold more active than BPP9a in potentiating rat paw edema elicited by BK: b) like BPP9a, KPP is specific in potentiating kinin-induced edema, being ineffective in potentiating edema induced by histamine or serotonin; and c) DesArg9-BK (DABK) elicits a small edematogenic response which can be potentiated by both KPP and BPP9a. PMID- 1862743 TI - Effects of aminoguanidine on pre- and post-irradiation regional cerebral blood flow, systemic blood pressure and plasma histamine levels in the primate. AB - Exposure to ionizing radiation causes hypotension, cerebral ischemia and release of histamine (HA). To investigate the relationship among these three responses, rhesus monkeys (Macaca mulatta) received aminoguanidine (AG) (1 mg/kg), then were given either 50 Gy whole-body irradiation or sham-irradiation. Monkeys receiving AG had lower mean arterial blood pressure (MABP) than saline-treated controls. Compared to controls, rCBF was lower in irradiated monkeys but pre-treatment with AG did not influence this effect. Among untreated, irradiated monkeys, HA levels were increased only at two minutes post-irradiation, but among AG-treated, irradiated monkeys, HA levels were higher at all times postirradiation. Radiation induced release of HA may be associated with radiation-induced hypotension and reduced rCBF, but failure of AG to alter rCBF suggests that released HA may not be the sole mediator of these effects. Because elevations in plasma HA are probably due to HA derived from degranulation of mast cells, release of other bioactive substances from mast cells may also influence these cardiovascular effects. Surprisingly, in sham-irradiated monkeys, AG alone had a slight but significant hypotensive effect. PMID- 1862744 TI - A comparison of synovial fluid concentrations of non-steroidal anti-inflammatory drugs with their in vitro activity. AB - For NSAIDs it has been widely accepted that prostaglandin inhibition is their mechanism of action in clinical use. Yet many other actions have been described, although it is unclear to what extent these may contribute to clinical activity. This review attempts to relate some of the experimental activities of NSAIDs to concentrations of drugs which occur in clinical use. Since it is assumed that to be effective a drug must reach its target site of action, synovial fluid concentrations for NSAIDs are considered. The resulting analysis suggests that prostaglandin inhibition is a viable mode of action for most, if not all, NSAIDs. However, some NSAIDS may rely as much, if not more, on other actions for their anti-inflammatory effect. PMID- 1862742 TI - The intracerebroventricularly administered mast cells degranulator compound 48/80 increases the pituitary-adrenocortical activity in rats. AB - The effect of brain mast cells degranulation by compound 48/80 on the pituitary adrenocortical activity, measured indirectly through corticosterone secretion, and the involvement of a histaminergic mechanism in that stimulation was investigated in conscious rats. All the drugs were given intracerebroventricularly (icv), histamine antagonists 15 min prior to compound 48/80. Compound 48/80 induced a significant dose- and time-related increase in the serum corticosterone levels. That increase, measured 1 h after administration of compound 48/80, was moderately diminished by icv pretreatment of rats with mepyramine and cimetidine, histamine H1- and H2-receptor antagonists. Three hours after administration of compound 48/80 mast cells of the thalamus and the hypothalamus were completely degranulated. At the same time the thalamus and the whole brain histamine levels were substantially higher than in the saline-treated control rats. The above results suggest that histamine liberated from the brain mast cells and central histamine receptors play a moderate role in increasing the pituitary-adrenocortical activity by compound 48/80. PMID- 1862745 TI - Extracellular phospholipase A2 detected at inflamed sites in rats does not originate from platelets. AB - Extracellular phospholipase A2 activity has been detected in caseinate-induced peritoneal fluid in rats. We studied the source of this extracellular phospholipase A2 in 'platelet-poor' rats which had been pretreated with an intravenous injection of rabbit anti-rat platelet serum. In these rats, the increase in the peritoneal fluid extracellular phospholipase A2 level at the inflamed sites was almost identical to that observed in control rats, although platelet numbers in peripheral blood were decreased markedly. This observation suggests that extracellular phospholipase A2 in the peritoneal cavity is not derived mainly from platelets. PMID- 1862747 TI - Tenoxicam concentrations in synovium and joint cartilage in humans. AB - Tenoxicam is an NSAID of the oxicam group. Its distribution in articular tissues was investigated in 12 patients who required total arthroplasty of the hip. They were given tenoxicam 20 mg once daily for 8 to 30 days before surgery. Blood, synovium and cartilage samples were taken concurrently during surgery, about 14 hours after the last tenoxicam dose. The tissues were ground using a freeze grinder. Tenoxicam was assayed by HPLC. Tenoxicam concentrations averaged 6.21 +/ 3.81 micrograms/ml in plasma, 7.56 +/- 4.67 micrograms/g in synovium and 2.05 +/ 1.43 micrograms/g in cartilage. The individual synovium/cartilage ratios ranged from 1.9 to 9.7. Finally tenoxicam exhibited more affinity for its target organ (synovial tissue) than for joint cartilage. PMID- 1862746 TI - A23187-induced pulmonary gas trapping and inflammation in the guinea pig. AB - A brief A23187 aerosol exposure produced prolonged airway obstruction with granulocyte accumulation in conscious guinea pigs. Aminophylline, atropine, pyrilamine, salbutamol, SC-41930 (a leukotriene B4 antagonist) and WEB 2086 (a platelet activating factor antagonist) were administered intravenously (i.v.) to evaluate their ability to prevent these changes. Inhaled salbutamol was also assessed. Aminophylline, atropine, and salbutamol (i.v. and aerosol) inhibited A23187-induced gas trapping (p less than 0.01). However, pyrilamine, SC-41930 and WEB 2086 did not influence this airway obstructive effect. Only atropine, inhaled salbutamol and SC-41930 inhibited the cell influx (p less than 0.01), while pyrilamine potentiated the inflammation (p less than 0.05). We conclude that A23187 produces a sustained bronchospasm and an intense granulocyte accumulation. The treatment agents tested differ considerably in their ability to alter A23187 induced airway obstruction and inflammation. PMID- 1862748 TI - Oxidation of articular cartilage glyceraldehyde-3-phosphate dehydrogenase (G3PDH) occurs in vivo during carrageenin-induced arthritis. AB - Articular cartilage proteoglycan biosynthesis was substantially inhibited by the competitive glycolytic inhibitor 2-deoxyglucose (approximately 65% at 100 mM), but to a much lesser degree (approximately 10%) by the oxidative phosphorylation uncoupler, 2,4-dinitrophenol. These results confirm that articular cartilage proteoglycan synthesis mostly utilises ATP which is generated by glycolysis. In addition, we have utilised the loss of the relatively specific labelling of glyceraldehyde-3-phosphate dehydrogenase (G3PDH) by [3H]-iodoacetic acid to show that rabbit articular G3PDH is oxidised in vivo during the animal model of acute arthritis, carrageenin-induced arthritis, in the same way as we have previously shown that cartilage G3PDH is oxidised after in vitro exposure to sublethal doses of H2O2. The oxidation of rabbit G3PDH in vivo (18 hr post-injection) corresponds with the maximal influx of PMNL cells into the arthritic synovial fluid and with substantial inhibition of proteoglycan core protein synthesis. We propose that H2O2 released from "activated" PMNLs and macrophages is responsible for the "down regulation" of biosynthetic processes found in cartilage during acute inflammation. PMID- 1862750 TI - Hypotensive action of IgG preparations containing aggregates is suppressed by PAF receptor antagonist BN 52021 and by gadolinium chloride (an agent blocking Kupffer cell function). AB - The hypotensive side effect of four IgG preparations was studied in a rat model. An unmodified, chromatographically isolated preparation (prepn. C) appeared to induce a transient drop in blood pressure via the kininogen kinin system. A preparation made by ethanol fractionation (prepn. E) and an ethanol-fractionated, modified product (prepn. M) produced an action which does not depend on kininogen activation. No blocking of kininase was required for this effect and it was brought about by prepn. M was devoid of any sizeable prekallikrein activator or kallikrein like proteinase content. The effect was associated by the aggregate fraction of prepn. E, but not with IgG monomers of the same preparation. Animals given these latter types of IgG preparations were refractory to a second dose 24 hours later. The involvement of PAF in the kinin-independent hypotensive action is suggested by the finding that PAF-receptor antagonist BN 52021 prevented the effect and returned the blood pressure close to normality when given during hypotension. A blockade of Kupffer cells brought about by administration of GdCl3 was also found to prevent the effect pointing to the involvement of these type of cells in the reactions. PMID- 1862751 TI - Comparative study of in vitro inhibition of activation of the classical and alternative pathways of human complement by the magnesium and sodium salts of the anti-inflammatory peptide N-acetyl-aspartyl-glutamic acid (NAAGA). AB - The inhibitory activity of the sodium salt of the anti-inflammatory peptide N acetyl-aspartyl-glutamic acid (NAAGA) on activation of the classical and alternative pathways of human complement was compared with that of the clinically used magnesium salt of NAAGA (NAAGA-Mg). Sodium salt of NAAGA (NAAGA-Na) inhibited both pathways of activation in a dose-dependent manner at concentration ranging from 1 to 10 mM by acting on formation and/or function of the C3 convertases as shown by the inhibitory capacity of the peptide on the release of the C3 cleavage fragment C3b and C3a. NAAGA-Na was as effective as NAAGA-Mg in inhibiting classical pathway activation at concentration above 10 mM. NAAGA-Na was more effective than NAAGA-Mg in inhibiting the alternative pathway since the sodium salt did not interfere with Mg-dependent formation of the alternative pathway C3 convertase. PMID- 1862749 TI - Different inhibitory actions of cyclosporine A and cyclosporine A-acetate on lipopolysaccharide-, interleukin 1-, 1,25 dihydroxyvitamin D3- and parathyroid hormone-stimulated calcium and lysosomal enzyme release from mouse calvaria in vitro. AB - The effects of cyclosporine A (CsA) and one of its immunologically inactive structural analogues, cyclosporine A acetate (CsA-A) on lipopolysaccharide (LPS) , interleukin-1 (IL-1)-, 1,25 dihydroxyvitamin D3 (1,25 D3)- and parathyroid hormone (PTH)-stimulated bone resorption were tested in mouse calvaria cultures. The release of calcium and a lysosomal enzyme, N-acetylglycosaminidase (NAG) was determined after 3 days of culture. All bone resorbing agents potently stimulated calcium and NAG release. At therapeutic concentration levels of 0.1 and 1.0 micrograms/ml, the immunologically active CsA was significantly more potent than the inactive CsA-A against LPS- and 1,25 D3-induced calcium and NAG release. The inhibition by both cyclosporines of IL-1 and PTH stimulated calcium release was not significantly different. CsA was however more potent than CsA-A against IL-1 stimulated NAG release. PTH-stimulated NAG release was not inhibited by CsA or CsA-A. These findings suggest that both cyclosporines interfere with more than one mechanism of activation of bone resorption. The specific effect of CsA against LPS and 1,25 D3 may be related to its known inhibition of immune cell derived cytokine expression. PMID- 1862752 TI - Effect of PAF on erythrocyte membrane heterogeneity: a fluorescence study. AB - The effect of platelet activating factor, PAF, on the erythrocyte membrane heterogeneity was investigated by measuring the steady-state fluorescence anisotropy and fluorescence decay of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5 hexatriene (TMA-DPH) incorporated in hemoglobin-free erythrocyte membranes. PAF induced a significant increase of the lipid order in the exterior part of the membrane and a decrease in membrane heterogeneity. These results indicate that PAF may cause changes in the physico-chemical structure of the erythrocyte membrane. PMID- 1862754 TI - Treatment of early-stage breast cancer. Many questions, a few answers. PMID- 1862755 TI - Can pleasure be quantified in dollars? PMID- 1862756 TI - The rule of rescue. PMID- 1862753 TI - Mechanisms of oxidant-induced changes in erythrocytes. AB - There is an increasing body of experimental studies demonstrating the toxic effects of oxygen-derived free radicals. Evidence supports an important role for free radicals in ischemic injuries, inflammation, and chemical-induced tissue injury. Free radicals are involved in normal biochemical processes like oxidative reduction and cellular metabolism; however, they also mediate disease processes. The participation of oxygen free radicals in lysis of red cells is important in some situations of intravascular hemolysis. This article will review neutrophil derived oxygen free radicals, emphasizing: (1) their effects on the erythrocyte and (2) how these effects may be attenuated. PMID- 1862757 TI - Liver units in three dimensions: I. Organization of argyrophilic connective tissue skeleton in porcine liver with particular reference to the "compound hepatic lobule". AB - Liver units were investigated in pig livers by means of histologic serial tracing, physical model building, and computer-aided three-dimensional imaging. Observations of the argyrophilic connective tissue skeleton were based mainly on the celloidin-embedded serial sections treated with silver impregnation. The parenchymal mass that clothed the initial segments of hepatic venous radicles was demarcated by fibrous septa which formed isolable units with two basic patterns: the simple hepatic lobule (SHL) and the compound hepatic lobule (CHL). Both lobule types presented regular limiting structures circumscribing each unit. Three-dimensional studies revealed that 25% of the lobules in a section belonged to the SHL type and 75% to the CHL type, the latter being predominant among the surface lobules. When considered in only two dimensions, however, the SHL-like lobules constituted the majority. Polygonal analysis disclosed that the pentagonal lobule was the most typical, instead of the "hexagonal" or "classic" lobule. The CHLs represented a multiaxial unit containing a system of venous tributaries in accordance with intralobular septation, whereas the SHLs were found with one axial vessel having a dendritic tendency at the incipient end; some SHLs were drained eccentrically by separate vessels into a sublobular vein. It was observed that, in dividing CHLs, whereas particular sinosoids were transformed into portal twigs, other sinusoids were changed into central venous tributaries. Fibrous deposition occurred along the septal-line sinusoids, bringing into view the septum-initiating plane. Fibroconnective tissue was supplied from the portal area and central (sublobular) adventitia, where portal triad structures and adventitial arterioles, respectively, were included. The findings of the present study facilitate the understanding of several characters of the lobules that have been reported previously, or occasionally postulated, such as the portal-central bridging tendency, the intralobular arterioles or ductules, the translobular artery or portal vein, the "portal-portal" or "portal central" anastomoses, and the apposition of pericentral zone close to periportal zone. Based on differences in argyrophilia of sinusoidal reticulum, in proportion of lobule types, and in vasculature, the anatomic heterogeneity of liver unit was demonstrable in zonality, regionality, and locality. PMID- 1862758 TI - Distribution of five peptides, three general neuroendocrine markers, and two synaptic-vesicle-associated proteins in the spinal cord and dorsal root ganglia of the adult and newborn dog: an immunocytochemical study. AB - This study describes the immunocytochemical distribution of five neuropeptides (calcitonin gene-related peptide [CGRP], enkephalin, galanin, somatostatin, and substance P), three neuronal markers (neurofilament triplet proteins, neuron specific enolase [NSE], and protein gene product 9.5), and two synaptic-vesicle associated proteins (synapsin I and synaptophysin) in the spinal cord and dorsal root ganglia of adult and newborn dogs. CGRP and substance P were the only peptides detectable at birth in the spinal cord; they were present within a small number of immunoreactive fibers concentrated in laminae I-II. CGRP immunoreactivity was also observed in motoneurons and in dorsal root ganglion cells. In adult animals, all peptides under study were localized to varicose fibers forming rich plexuses within laminae I-III and, to a lesser extent, lamina X and the intermediolateral cell columns. Some dorsal root ganglion neurons were CGRP- and/or substance P-immunoreactive. The other antigens were present in the spinal cord and dorsal root ganglia of both adult and newborn animals, with the exception of NSE, which, at birth, was not detectable in spinal cord neurons. Moreover, synapsin I/synaptophysin immunoreactivity, at birth, was restricted to laminae I-II, while in adult dogs, immunostaining was observed in terminal-like elements throughout the spinal neuropil. These results suggest that in the dog spinal cord and dorsal root ganglia, peptide-containing pathways complete their development during postnatal life, together with the full expression of NSE and synapsin I/synaptophysin immunoreactivities. In adulthood, peptide distribution is similar to that described in other mammals, although a relative absence of immunoreactive cell bodies was observed in the spinal cord. PMID- 1862759 TI - Development of the discoidal hemochorial placenta in the black mastiff bat, Molossus ater: evidence for a role of maternal endothelial cells in the control of trophoblastic growth. AB - In an effort to define further the factors that can influence trophoblastic growth, development of the discoidal chorioallantoic placenta was examined histologically in laboratory-bred black mastiff bats, Molossus ater. This placenta normally forms only at the cranial end of the right uterine horn. Its positioning was found to be related to the development of an unusual vascular tuft in the endometrium at this site following ovulation. When a decidual reaction occurred, the endothelial cells of the tuft vessels hypertrophied and their basal laminae became more prominent in sections stained for glycoproteins. Cytotrophoblast then proliferated preferentially around the tuft in the right horn and its vessels became surrounded by trophoblastic cuffs. A functional placenta was formed when trophoblastic tubules grew out from these cuffs, became interconnected, developed lumina, and began to carry maternal blood. Maternal endothelial cells generally persisted only in portions of the larger vascular tubules. These observations suggest that the endothelial cells of the tuft vessels may be secreting factors that influence early trophoblastic growth and are at least partially incorporated into the basal laminae of the endothelial cells. Evidence is reviewed which raises the possibility that endometrial endothelial cells might have a similar morphogenetic role in many other mammals with invasive trophoblast. Mitotic activity in the trophoblastic tubules of M. ater ceased when the tubules became patent and began to carry blood. Further growth was then accomplished by hypertrophy of the existing cytotrophoblast cells. Electron microscopic examination of near-term placentas confirmed that the interhemal barrier was hemomonochorial and lacked a continuous layer of syncytiotrophoblast. PMID- 1862760 TI - Changes in ultrastructure of transport systems and in rates of progestin secretion in the corpus luteum during late pregnancy in the rat. AB - Morphometric studies have confirmed that the corpus luteum (CL) of the pregnant rat contains luteal cells with numerous microvilli which directly face an extensive network of sinusoidal capillaries. From this it has been suggested that extensive development of transport structures is necessary to support progesterone synthesis and secretion. The present study was carried out to determine whether these transport structures could be related quantitatively to different rates of total progestin (progesterone plus 20 alpha-hydroxypregn-4-en 3-one) secretion reported to be 32, 10, and 23 micrograms/hr per ovary on day 16 and the morning (AM) and afternoon (PM) of day 22, respectively. Histological analysis was carried out on two CL, fixed by immersion, from each of five rats, at each stage of gestation. The important findings to emerge were that when the progestin secretion rate was greater, there was a significant increase in surface specializations on the luteal cell and a thickening of the capillary walls. There was also a greater volume of interstitial space between luteal cells and capillaries. However, due to the development of microvilli and unevenness in the capillary wall, the physiological diffusion distance (harmonic distance) between luteal cell cytoplasm and blood was not increased. Collectively, these results show that changes in the rate of progestin secretion are accompanied by significant, although disproportionate, changes in transport structures and suggest that the latter are important in supporting luteal function. PMID- 1862761 TI - Chemotherapy of disseminated Merkel-cell carcinoma. AB - Six patients developed metastatic merkel-cell carcinoma and were treated with a combination chemotherapy frequently used for small-cell lung cancer. Five of six patients had a complete response for a median of 3.5 months. Overall survival from initiation of chemotherapy was a median of 6.5 months. Two patients died from major complications of therapy. PMID- 1862762 TI - Is post-operative intracavitary therapy a necessary component of treatment for carcinoma of the endometrium? AB - The role of intracavitary therapy in combination with external pelvic radiotherapy for endometrial carcinoma remains controversial. To determine the pelvic failure rat in patients receiving only external pelvic radiotherapy following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) for carcinoma of the endometrium, we undertook a retrospective review of all patients referred to the Radiation Oncology Department from January 1977 through December 1984. Patients with grade I, superficially invading tumors were excluded from this analysis. 52 patients were eligible for the study. Three patients who were lost to follow-up immediately after completion of external beam irradiation were excluded, leaving a total of 49 evaluable patients. The median follow-up time is 61 months. Pelvic failure was seen in only 2 patients (4%), both of them occurring concurrent with distant disease. No vaginal vault failures were observed. Overall actuarial survival at 5 years was 82%. We conclude that external beam pelvic radiotherapy alone without intracavitary boost appears to be an adequate treatment for patients undergoing TAHBSO for carcinoma of the endometrium. PMID- 1862763 TI - The integration of whole abdominal radiotherapy and intraperitoneal cisplatin into the primary management of advanced ovarian carcinoma. AB - Eleven women with Stages III and IV epithelial ovarian carcinomas were entered into a protocol consisting of concurrent whole abdominal radiotherapy and intraperitoneal cisplatin followed by additional intraperitoneal cisplatin. The entire abdomen received 20 Gy in 20 fractions with no renal or hepatic shielding. Intraperitoneal cisplatin dosage was 20 mg/m2 weekly during radiation and 90 mg/m2 monthly thereafter for an additional three courses. Patients with Stages IIIC and IV had a median survival of 18 months and a two-year actuarial survival of 32%. Primary failure sites were the abdomen, pleura, and lymph nodes. Acute toxicity during radiotherapy was comparable to patients treated with radiation alone. No chronic renal, hepatic, or enteric complications were observed. Although the protocol did not have substantial efficacy in advanced disease, its toxicity was moderate enough to consider its use in less advanced cancers with peritoneal metastases. In particular, the protocol can be considered for women with ovarian cancer with no gross residuum and for women with papillary serous carcinoma of the uterine corpus. PMID- 1862764 TI - Carboplatin, methotrexate and vinblastin (Carbo-MV) for advanced urothelial cancer. A phase II trial. AB - Fifteen patients with advanced urothelial cancer were treated with carboplatin 300 mg/m2, methotrexate 30 mg/m2, and vinblastin 3 mg/m2 on day 1 and the same dosage of methotrexate and vinblastin on days 15 and 22. Six patients were pretreated with radiotherapy and or chemotherapy; 7 patients had impaired renal function due to obstructive uropathy. Eight patients achieved a partial remission; 4 patients achieved a minor remission or stabilization of progressive disease. Mean duration of response was 8+ month (2+ to 12+ month). Subjective tolerance of the treatment was excellent but there was considerable bone marrow toxicity in the pretreated patients. The data show that Carbo-MV (carboplatin, methotrexate, and vinblastin) is effective and subjectively well tolerated in advanced urothelial carcinoma. PMID- 1862765 TI - Dose-related alpha-difluoromethylornithine ototoxicity. AB - We assessed the ototoxicity associated with oral alpha-difluoromethylornithine (DFMO) administration in 58 patients with metastatic malignant melanoma. One hundred seventy-nine sequential audiograms obtained from patients treated with DFMO alone (16 patients) or in combination with alpha 2b-interferon (42 patients) were evaluated. DFMO doses ranged from 2 to 12 g/m2/d and were given over periods of 2 to 50 weeks. Total doses ranging from 60 g/m2 to 1390 g/m2 were correlated with clinical effects and pure tone audiometric changes. By regression analysis cumulative DFMO dose showed a consistent and statistically significant positive relationship to hearing loss at multiple frequencies (500, 1000, 2000, 4000, and 8000 Hz). Patients with normal (threshold less than 30 db) baseline audiograms demonstrated more hearing loss than those with abnormal (threshold greater than or equal to 30 db) baseline audiograms at the higher frequency levels. Of the patients with normal prestudy hearing thresholds 10% or less developed a demonstrable hearing deficit at cumulative DFMO doses below 150 g/m2. Conversely, up to 75% of the patients who received more than 250 g/m2 developed a clinically demonstrable hearing loss. Other factors which adversely affected hearing included age, male gender, and the concomitant use of alpha 2b-interferon. In summary, the risk of clinically significant hearing loss in patients treated with DFMO was primarily related to dose and the presence of a pre-existing hearing deficit. PMID- 1862767 TI - Cervical cancer: women aged 35 and younger compared to women aged 36 and older. AB - One hundred fifty-three patients with invasive cervical cancer were evaluated and treated at one of the two teaching hospitals of the Intergrated Ob-Gyn Residency Program of Wright State University, Dayton, Ohio, from 1 July 1983 to 30 June 1989. Sixteen patients with recurrent cervical cancer who initially had received their treatment elsewhere were excluded. Forty-one of the 137 newly diagnosed patients with cervical cancer were aged 35 years or less. This review was undertaken because of frequent reports of the increasing incidence of cervical cancer in women aged 35 and under. Some reports also reveal a worse prognosis for the younger age group. This investigation provided the opportunity to evaluate cervical cancer patients aged 35 and under and compare the results to the evaluations of women aged 36 and over. Evaluation of age, stage, presenting symptoms, number of positive lymph nodes, pap smear history, pregnancy within 1 year of diagnosis, treatment, and survival was carried out in patients aged 35 years and less and compared to their older counterparts aged 36 and over with cervical cancer. PMID- 1862766 TI - A phase II trial of gallium nitrate (NSC #15200) in previously treated ovarian carcinoma. A Gynecologic Oncology Group Study. AB - Twenty-six evaluable patients with advanced or recurrent epithelial ovarian cancer were treated with 750 mg/m2 of gallium nitrate every three weeks. All patients had prior cisplatin chemotherapy. One patient had a complete response (3.8%), two patients had partial responses (7.7%), and six patients had stable disease (23.1%). The 95% upper confidence bound for response is 27.2%. The major toxicity was nausea and vomiting which was modest, and anemia, which was moderate to severe. Myelosuppression was minimal. Gallium nitrate has modest activity in previously treated patients with epithelial ovarian cancer. PMID- 1862768 TI - Phase II trial of etoposide (V), adriamycin (A), and cisplatinum (P) in patients with metastatic gastric cancer. AB - The efficacy and toxicity of a combination of etoposide (100 mg/m2 i.v. on days 1 to 3), Adriamycin (20 mg/m2 i.v. on days 1 and 8) and cisplatinum (40 mg/m2 i.v. on days 2 and 8) repeated every 4 weeks as an outpatient regimen were assessed in 29 consecutive patients with metastatic gastric cancer with measurable disease. Five of these patients were refractory to 5-Fluorouracil, Adriamycin, and Mitomycin C. Three of these previously treated patients responded to the etoposide. Adriamycin, cisplatinum (VAP) therapy. An overall objective response rate of 72.5% was achieved, including 14% that were complete responses. The median duration of response was 6.0 months; median overall survival was 7.2 months, overall one-year survival was 34.4%. Hematologic toxicity was intense, particularly among patients with lower performance status. Three patients died as a consequence of nadir sepsis episodes. PMID- 1862769 TI - Preoperative chemoradiotherapy for adenocarcinoma of the pancreas. Rationale and technique. PMID- 1862770 TI - Evolution of the French-American-British (FAB) proposals. Is there a place for acute basophilic leukemia? PMID- 1862771 TI - Acute basophilic leukemia. A clinical, morphologic, and cytogenetic study of eight cases. AB - The authors describe eight cases of acute basophilic leukemia. In six of the eight cases, basophilic involvement was not apparent by light microscopic examination. The cases were identified on the basis of ultrastructural evidence for basophil/mast cell differentiation of the blasts with little or no differentiation into other lineages. Ultrastructural analysis revealed immature basophil granules in blasts in all eight cases and theta granules in blasts in four cases. In three cases, ultrastructural evidence of mast cell differentiation also was present, with rare cells showing evidence for both basophil and mast cell differentiation. No clinical features distinguished this group of patients from others with acute myeloid leukemia. Cytogenetically, the cases were heterogeneous. Three had a Philadelphia chromosome; none had a t(6;9). The authors conclude that ultrastructural analysis usually must be used to diagnose acute basophilic leukemia, that acute basophilic leukemia is associated frequently with the Philadelphia chromosome, and that the ultrastructural findings provide evidence for a common origin of basophils and mast cells. PMID- 1862772 TI - Immunoblastic lymphoma with abundant clear cytoplasm. A comparative study of B- and T-cell types. AB - The morphologic, phenotypic, molecular genetic, and clinical features of 34 cases of clear-cell immunoblastic lymphoma (IBLC) are described. Sixteen cases were of B-cell type (IBLC-B) and 18 cases were of T-cell type (IBLC-T). There were no significant differences in the morphologic characteristics of the neoplastic cells in the two types, although IBLC-B was less likely to be polymorphic than IBLC-T. Interfollicular proliferation, a higher mitotic rate, infiltration by eosinophils, and an increase in capillary-sized blood vessels were also features of IBLC-T, whereas necrosis and fibrosis were more extensive in IBLC-B. Patients with IBLC-B were predominantly female, whereas those with IBLC-T were predominantly male. The mean age was 62 years for those with IBLC-B and 46 years for those with IBLC-T. Patients with IBLC-B usually had lower-stage disease, but there was no significant difference in survival rate between those with IBLC-B and those with IBLC-T. Although most cases of IBLC have been considered to be of peripheral T-cell origin, the authors conclude that IBLC-B is more common than previously considered and that clear-cell morphologic characteristics are not a reliable indicator of T-cell type. PMID- 1862773 TI - Non-Hodgkin's lymphomas of nasal cavity and paranasal sinuses. An immunohistochemical study. AB - The authors studied the immunophenotype of nine sinonasal lymphomas using a panel of monoclonal antibodies that react with fixed, paraffin-embedded material (EMA, CAM 5.2, CD45, CD37 [MB-1], MB-2, L-26, CDw75 [LN-1], CD45RA [4 KB-5], CD43 [MT 1], and CD45RO [UCHL-1]). There were seven men and two women, with a mean age of 64 years (range, 9-89 years) and median age of 56 years. Three tumors were limited to the nasal cavity, and the other six had multiple sites of involvement, including the nasal cavity (five), antrum (six), ethmoid (two), orbit (two), and hard palate (one). Histologically, one was a lymphoblastic lymphoma (LBL), one was small cleaved-cell lymphoma (SCCL), three were mixed-cell lymphomas (MCLs), and four were large cell lymphomas (LCLs). Four cases were T-cell lymphomas (one SCCL, three MCLs), four were B-cell neoplasms (four LCLs), and one was of uncertain lineage (LBL). Angioinvasion, coagulative necrosis, and epitheliotropism were seen in the T-cell lymphomas. Extranasal dissemination was seen in four cases: one LBL that involved the lymph nodes, skin, and testes 15 months after diagnosis; one B-LCL that involved the skin 9 months after diagnosis; and one B-LCL and one T-MCL that involved the gastric mucosa and lung simultaneously with nasal presentation. This study shows a higher predominance of B-cell lymphomas in the sinonasal region than previously reported in Oriental populations. However, the T:B ratio of these lymphomas is still greater than that observed for primary lymph node-based neoplasms. PMID- 1862775 TI - Use of fluorescent in situ hybridization for marker chromosome identification in congenital and neoplastic disorders. AB - Identifying marker chromosomes of unknown origin in the clinical cytogenetics laboratory has been a problem historically, despite advances in specialized staining techniques. Determination of the origin of these marker chromosomes in patients with congenital or malignant neoplastic disorders is essential for more complete diagnosis, counseling, and treatment. The authors describe the use of fluorescent in situ hybridization with chromosome-specific alpha-satellite DNA probes to identify the origin of marker chromosomes in two patients with congenital disorders and three patients with malignant neoplastic disorders. The impact of firm identification of the marker chromosome for the diagnosis of these patients is discussed. The authors also discuss the feasibility of using this technique routinely in the clinical cytogenetics laboratory. PMID- 1862774 TI - A case of acquired factor X deficiency with in vivo and in vitro evidence of inhibitor activity directed against factor X. AB - A 67-year-old woman had symptoms of an upper respiratory tract infection for which she received a five-day course of erythromycin. Epistaxis and gross hematuria subsequently developed, and the patient was found to have a selective Factor X deficiency. She received supportive therapy and prothrombin complex concentrates (Factors II, VII, IX, and X), with subsequent resolution of her transient Factor X deficiency. Her hospital course, however, was complicated by the development of multiple cerebral infarctions. This is the tenth reported case of transient Factor X deficiency not associated with amyloidosis. In seven of the previous cases, as in this patient, the deficiency was associated with a preceding upper respiratory infection. This is the only case, however, with evidence of inhibitory activity in the plasma that was directed toward Factor X. PMID- 1862778 TI - Multitumor "sausage" blocks in immunohistochemistry. Simplified method of preparation, practical uses, and roles in quality assurance. AB - This report describes a simplified method for preparing multitumor sausage blocks (MTSBs) for use in immunohistochemical procedures. Rather than relying on previously processed paraffin blocks as a source of material, this procedure involves procuring tissue at the time of gross specimen examination. The tissue is processed along with routine surgical pathologic material, and the paraffinized samples are placed in "storage cassettes" for easy cataloging and storage. Thin strips are cut from the tissue in the "storage cassettes" and combined by dripping liquid paraffin onto them while they are rolled between the thumbs and forefingers, somewhat like making a cigarette. This results in a tissue "log." Transverse sections of the "log" are embedded in paraffin blocks and used as MTSBs. Practical uses of MTSBs are discussed, and their role in quality assurance is stressed. PMID- 1862777 TI - Congenital atransferrinemia. A case report and review of the literature. AB - A four-year-old Polynesian girl with a two-year history of severe microcytic, hypochromic anemia (which was refractory to iron therapy) had a decreased beta globulin fraction on serum protein electrophoresis, resulting from the absence of the transferrin (TRF) band. Subsequent assays for TRF showed a level below the detectable range. Liver biopsy revealed significant deposition of hemosiderin within hepatocytes and Kupffer cells, in addition to early fibrosis. Two bone marrow aspirates were hypercellular, with decreased myeloid-erythroid ratios. This case represents the eighth reported example of congenital atransferrinemia, a rare, apparently autosomal recessive disease. PMID- 1862776 TI - Achromobacter xylosoxidans. An unusual neonatal pathogen. AB - Perinatal acquisition of a rare pediatric pathogen, Achromobacter xylosoxidans, with evidence for in utero transmission, is described. Cultures from the mother and neonate demonstrated A. xylosoxidans. An ascending bacterial infection in the mother with clinical chorioamnionitis is presented as the probable mode of transmission. Postmortem examination of the infant confirmed Achromobacter meningitis. In contrast to the current case with transmission from mother to neonate, previously published neonatal cases of Achromobacter infections indicate that nosocomial transmission of the organism is most common (79%). In addition, the literature review revealed a high mortality associated with meningitis (77%), frequent hydrocephalus, and subsequent neurologic sequelae (36%). To the authors' knowledge, this is the first documented case of maternal-fetal transfer of A. xylosoxidans. PMID- 1862779 TI - Expression of haptoglobin-related protein in primary and metastatic breast cancers. A longitudinal study of 48 fatal tumors. AB - The ability to establish a prognosis for patients with early breast cancer is an important clinical issue. Recent studies have shown that antibodies to haptoglobin-related protein (Hpr) may be useful in stratifying early patients with breast cancer according to their relative risks of recurrence. Nearly 30% of early breast cancers express proteins bearing Hpr epitopes. Hpr-positive breast cancers are more likely to recur after primary resection and are associated with shorter disease-free intervals. This immunohistochemical study examines temporal changes in Hpr expression during the course of disease in 48 patients with fatal breast carcinoma. Thirty-seven primary tumors (77%) were Hpr positive. Ten of the 11 initially negative tumors (91%) were Hpr positive at the time of recurrence. In contrast, only 10 of the 37 initially positive tumors (27%) were Hpr negative with relapse. Of 18 axillary nodes that were examined, 16 (89%) were Hpr positive; all four lymph nodal metastases in patients with initially negative primary tumors were Hpr positive. The authors conclude that the acquisition of Hpr expression parallels increased malignant potential and that Hpr expression, once acquired, tends to remain a permanent characteristic of any given mammary tumor. PMID- 1862780 TI - Sex cord tumor with annular tubules associated with endometriosis of the fallopian tube. AB - Sex cord tumor with annular tubules (SCTAT) is a distinctive ovarian sex cord stromal tumor. The authors describe a case of SCTAT arising outside the ovaries, in the fallopian tube. The authors are aware of only one other case of extra ovarian SCTAT, in an umbilical hernia sac in an adult woman. The case reported was an incidental finding in a hysterectomy specimen, obtained because of carcinoma in situ of the uterine cervix in a 32-year-old woman. The patient is alive and disease-free two years after surgery. The 1-cm tumor in the right fallopian tube was composed of typical ring-shaped tubules encircling hyalinized basement membrane-like material. In addition, glands and stroma of endometriosis were intimately admixed with the nests of tumor. The implications of these findings for the origin of SCTAT and ovarian sex cord structures are discussed. PMID- 1862782 TI - Plastic embedding for immunohistology. PMID- 1862781 TI - An autopsy case of I-cell disease. Ultrastructural and biochemical analyses. AB - An autopsy case of I-cell disease in a 4-year-old Japanese girl is presented. In this report, the authors analyze the relationship between morphologic (including electron microscopic) and biochemical findings. Lymph node, spleen, and kidney, which were stained with Hale's colloidal iron method, contained large amounts of hexosamine. These substances had accumulated in lymphocytes of B-cell lineage. PMID- 1862783 TI - Plasmacytoid acute T-cell lymphoma/leukemia. PMID- 1862784 TI - Drug-induced immune hemolytic anemia. PMID- 1862785 TI - Pneumocystis ocular infection. PMID- 1862787 TI - Amnestic effects of intravenous diazepam in healthy young men. AB - Changes in a test of memory performance were evaluated in 103 healthy young men after challenges with placebo and two different doses of intravenous diazepam (0.12 and 0.20 mg/kg). Both diazepam doses significantly impaired free recall in a dose-dependent manner. Within each dose challenge there was no significant correlation between the average serum diazepam or desmethyldiazepam levels and the average number of words recalled across the time points. The data expand our current understanding of the amnestic effects of benzodiazepines and suggest that patients abusing these drugs in large doses may develop profound degrees of memory impairment. PMID- 1862788 TI - Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence. AB - We conducted a single-blind, random assignment, placebo-controlled, 12-week comparison of desipramine hydrochloride and amantadine hydrochloride as adjunctive treatments to counseling for cocaine dependence. Subjects were 54 outpatients who met DSM III-R criteria for active cocaine dependence and who completed a minimum of 2 weeks of treatment. Subjects treated with fixed doses of 200 mg/day desipramine (N = 17), 400 mg/day amantadine-placebo (N = 16), and placebo (N = 21) did not differ for lifetime cocaine use, lifetime histories of psychopathology, admission scores on psychometric assessments, and sociodemographics. All treatment groups demonstrated dramatic and persistent decreases in cocaine use, craving for cocaine, and psychiatric symptoms consequent to treatment. Although there was a trend for more dropouts by subjects taking desipramine, there were no significant differences among treatment groups regarding retention in treatment, craving for cocaine, and decreased cocaine use confirmed by urine toxicology. There was a trend for subjects treated with desipramine to maintain longer periods of cocaine abstinence. Mean plasma concentration of desipramine in a subsample of our subjects was less than that recommended for treatment of depression, thus the dosage of desipramine may have been subtherapeutic. PMID- 1862789 TI - Validity of the MCMI Drug Abuse Scale varies as a function of drug choice, race, and axis II subtypes. AB - The validity of the Drug Abuse Scale (T) from the Million Clinical Multiaxial Inventory (MCMI) was studied by administering the MCMI to 110 male veterans seeking treatment for opioid or cocaine dependence. Only 26 and 23% of the sample obtained base rate (BR) scores above the clinical relevant cutoffs of 84 and 74, respectively. Covariables associated with elevated scores on the T Scale were Black race, presence of narcissistic/antisocial personality features, and more severe psychopathology in general. The authors urge caution in using the Drug Abuse Scale for the purpose of identifying drug abusers. PMID- 1862786 TI - Treatment of heroin addicts using buprenorphine. AB - Thirty-nine opioid-dependent outpatients were treated with the partial agonist buprenorphine at 2 to 6 mg/day for 1 month. Treatment retention was good (72%), and illicit opioid use decreased from 50% overall to 17% for those who remained in treatment. Precipitated withdrawal symptoms were mild and related to dose of buprenorphine. At the end of this month, 28 subjects were abruptly discontinued from buprenorphine and given the antagonist naltrexone. Withdrawal symptoms from buprenorphine were quite mild, and naltrexone was initiated in 20 patients (51% of total or 71% of those 28 completing 30 days on buprenorphine), but only 4 patients (10% overall) were successfully maintained on naltrexone for at least 2 weeks. PMID- 1862790 TI - Clinical assessment and urine testing for anabolic-androgenic steroid abuse and dependence. AB - The emerging epidemic of anabolic-androgenic steroid use, no longer confined to elite athletes, is associated with adverse health consequences for which users may seek treatment. As with other forms of drug abuse, patients may deny or hide their use of steroids while seeking treatment for bothersome side effects or other problems. Thus, clinicians may increasingly, but unknowingly, see patients who are using steroids. Early detection and treatment of steroid abuse and dependence is critical in order to prevent serious and potentially fatal consequences. Therefore, it is incumbent upon clinicians to know the signs and symptoms of using steroids, and to be familiar with the clinical indications for urine testing. Using case examples, the authors review the assessment of steroid abuse and dependence in clinical practice and illustrate the role of urine testing in the assessment process. PMID- 1862791 TI - The relationship of solvent use to other substance use. AB - One hundred thirty solvent abusers were retrospectively identified from a family study containing 286 alcoholics, 157 felons, 60 control subjects, and 1,640 of their relatives. Comprehensive data regarding psychiatric diagnosis and drug use were gathered using the Home Environment Lifetime Psychiatric Record. Solvent abuse was very strongly associated with having a diagnosis of Antisocial Personality Disorder and was consistently associated with polysubstance abuse. Solvent abusers were more likely to be male, or lower socioeconomic status, and younger than those without a reported history of solvent abuse. Contrary to current understanding, solvent use did not clearly precede other substance use; rather, alcohol and cannabis use tended to occur first, followed by use of solvents. Solvent users were 5 to 10 times more likely than nonusers to report abuse of opioids, stimulants, depressants, and hallucinogens. PMID- 1862792 TI - Long-term trends in male drunkenness arrests in metropolitan Toronto: effects of social-setting detoxication centers. AB - Drunkenness arrest rates for adult males in Toronto decreased substantially during the period 1966 to 1987. In 1971 there was a change in legislation permitting police to take public inebriates to detoxication centers. Drunkenness rates continued to decline at a rate similar to that for the previous 3 years. The next year drunkenness arrests increased but subsequently declined at a rate which was 50% greater than that which preceded the change in legislation. Since 1973 year by year changes in the rate of male drunkenness arrests have not been consistently related to rates of police admission to detoxication centers or to total admissions to detoxication centers. The results suggest that recent trends in drunkenness arrests have been influenced by the 1971 change in legislation and the increased use of detoxication centers. However, the influence of other factors must also be considered. PMID- 1862793 TI - The role of formal law in alcohol control systems: a comparison among states. AB - Formal laws and regulations governing activities of state alcohol beverage control agencies in the United States were classified into 10 categories of physical availability and four categories of economic availability. These categories were subjected to similarity analysis to determine variation among states. Kruskal's stress-one measure revealed three major dimensions of alcohol control laws: forms of retail sales, administrative penalties for violations of alcohol control laws, and price restrictions. This finding suggests that the license/monopoly distinction frequently used to categorize state alcohol control systems is inadequate to characterize the variations in control systems. PMID- 1862794 TI - The adult children of alcoholics in a psychiatric population. AB - The issues confronting adult children of alcoholics (ACOA) are well publicized but their empirical basis remains limited. The screening of 250 consecutive psychiatric admissions to a general hospital revealed a significant prevalence of ACOAs across diagnoses. Compared to the other patients, the ACOA group was younger but with no other socioeconomic difference. The diagnoses of substance abuse and phobic disorders were more frequent. The group was psychiatrically hospitalized at an earlier age. The impact of an ACOA status varied with the parental biological relation and gender, and with the premorbid antecedents of parental alcoholism. PMID- 1862796 TI - Invited commentary: should arteriographic case-control studies be used to identify causes of atherosclerotic coronary artery disease? AB - Arteriographic case-control studies still have a role in defining associations and dose-response relations between newly purported risk factors and atherosclerotic coronary artery disease. They remain one of the better ways to sort out whether a risk factor acts to cause clinical coronary disease via effects on coronary atherosclerosis, infarction independent of atherosclerosis, or both. It remains unclear if the selection processes for coronary arteriography infuse bias into the selection of cases, though the report by Reed and Yano suggests it does not. Control group selection remains problematic, as it does for all case-control studies, and considerable effort should be exercised to avoid the many potential biases in selection of both cases and controls. In this latter statement there is agreement with authors Reed and Yano. However, the avoidance of arteriographic studies threatens to curb the initiation of that sequence of studies that can, in a relatively short duration of time, provide useful information on the potential for a risk factor intervention to inhibit coronary atherosclerosis and, possibly, clinical coronary events. This, then, raises the final point for emphasis. Arteriographic studies, be they case-control, prospective, or experimental, may be most powerful when paired with those using clinical endpoints. In addition to the chance for replication of findings with another set of endpoints, the issue of mechanism of action via the atherosclerotic process can be addressed. Interestingly, the Honolulu Heart Program, with its laudable efforts to collect both autopsy and arteriographic quantitations of atherosclerosis, provides perhaps the best illustration in the current literature of the power of using multiple endpoints for coronary artery disease to more completely elucidate the role of risk factors in the natural history of that disease. PMID- 1862795 TI - Predictors of arteriographically defined coronary stenosis in the Honolulu Heart Program. Comparisons of cohort and arteriography series analyses. AB - The purpose of this study was to determine if the major risk factors for clinical myocardial infarction also predicted coronary artery stenosis as defined by arteriography. Of a cohort of 7,591 men who were free of cardiovascular disease at entry, 357 had arteriographic studies during a 20-year follow-up period. Risk factor levels were therefore known prior to the onset of clinical symptoms and arteriographic studies. Men with arteriograms were divided into groups with and without prior clinical myocardial infarction. High blood pressure, serum cholesterol, obesity, and low alcohol intake predicted both severe coronary stenosis and incident myocardial infarction, thus indicating that these variables were associated with clinical events through the underlying process of atherosclerosis. Dietary intake of cholesterol and serum glucose also had similar but not always statistically significant patterns of association with both coronary stenosis and myocardial infarction. In contrast, serum triglyceride and cigarette smoking predicted clinical myocardial infarction, but not severe coronary stenosis. This suggests that these variables play a stronger role in the precipitation of acute clinical events than in the underlying process of atherosclerosis. The findings were quite different for several risk factors when analyzed in a case-control format using the arteriography series from this same data set. Examination of possible explanations for the differences raises questions concerning the use of arteriography series for etiologic studies of coronary atherosclerosis. PMID- 1862797 TI - Factors associated with high density lipoprotein cholesterol in Japanese and American telephone executives. AB - The association of plasma high density lipoprotein cholesterol (HDL cholesterol) with several factors was examined in a cross-sectional study of Japanese and American telephone executives. Mean HDL cholesterol levels were similar in both groups of men and were negatively associated with body mass index, smoking, and serum uric acid and positively associated with alcohol and exercise. These associations did not differ between the Japanese and the American men. The mean HDL cholesterol level was 4.2 mg/dl lower in the Japanese than in the American men after adjusting for age, body mass index, alcohol, smoking, exercise, and serum uric acid. The difference in HDL cholesterol between Japanese and American men in this study is inconsistent with the much lower coronary heart disease mortality in Japan and with previous comparison studies of these two populations. Most previous studies have not adjusted for important confounders, but the selective nature of our study groups may have also contributed to this inconsistency. These racial differences in HDL cholesterol may also be due to either genetic or unmeasured environmental and cultural differences. Given the similarity in HDL cholesterol levels between these two groups, our results suggest that HDL cholesterol does not play an important role in the lower coronary heart disease mortality in Japanese men. PMID- 1862798 TI - Coffee and cholesterol, an Italian study. AB - In the present study, conducted in northern Italy between 1986 and 1989, the authors investigated the possible association between coffee consumption and serum cholesterol levels in 8,983 subjects, 7,432 men and 1,551 women, managers and employees aged 18-65 years, who were examined during a program of preventive medicine upon an agreement between various companies and the Centro Diagnostico Italiano. Analysis of covariance was used to compare the serum cholesterol levels of the subjects subdivided according to coffee consumption, along with age, body mass index, alcohol consumption, cigarette smoking, and physical activity. An important relation was demonstrated between coffee intake and cholesterol, particularly in the men, the differences in serum cholesterol in the coffee users compared with the nonusers being 6.1 +/- 1.4 (standard error) mg/dl for consumers of 1-3 cups/day (3.4 +/- 1.4 mg/dl after adjustment for age, body mass index, alcohol and cigarette consumption, and physical activity), 9.9 +/- 1.6 mg/dl for those drinking 4-5 cups/day (5.8 +/- 1.6 mg/dl after adjustment), and 14.8 +/- 2.0 mg/dl for those drinking over 5 cups/day (9.6 +/- 2.0 mg/dl after adjustment). This relation remained substantially unvaried when nonsmokers and smokers were analyzed separately. It has been suggested that it is coffee prepared by boiling rather than other methods that has a hypercholesterolemic effect. Our observations demonstrate an interesting relation between coffee and cholesterol, even though the coffee drunk in Italy is mainly filtered and nonboiled. However, our finding is not necessarily in disagreement with the above hypothesis since, when coffee is prepared in the Italian way (with the mocha method), ground coffee is preheated by steam and more importantly, the water passes through the ground coffee at a higher temperature than with the other brewing methods. PMID- 1862799 TI - Cancer and polyps of the colorectum and lifetime consumption of beer and other alcoholic beverages. AB - Two parallel case-control studies were conducted in the Marseilles metropolitan area of France from 1979 to 1985 on cancers and adenomatous polyps of the colorectum. All cases of cancer (n = 389) and polyps (n = 252) were incident and histologically confirmed. Controls (n = 641) matched for sex and age were selected among patients undergoing functional reeducation for injury or trauma in one of five hospital centers. Intake of alcoholic beverages was investigated by questions on daily or weekly intake of wine, beer, aperitifs, and distillates during different life periods. Questions on alcoholic beverages were integrated in a detailed diet history interview questionnaire. The risk of rectal cancer was elevated in male beer drinkers (relative risk = 1.73, 95% confidence interval 1.01-2.95) and in men and women combined (relative risk = 1.71), while beer consumption was not associated with colon cancer. Total ethanol intake and consumption of wine and distillates were not associated with the risk of cancer of the colon or rectum, nor with risk of polyps. Adjustment in the statistical analysis for energy intake and for other dietary variables (fiber from fruits and fiber from vegetables), which were found to be risk factors in the study, did not substantially change the results found for beer and other alcoholic beverages. Etiologic hypotheses related to nitrosamine content of beer are discussed in the light of growing epidemiologic evidence that beer consumption specifically increases the risk of rectal cancer. PMID- 1862800 TI - A case-control study of diet and cancer of the pancreas. AB - In a population-based case-control study carried out in Adelaide, South Australia, during the years 1984-1987, the diets of 104 cases of cancer of the pancreas 1 year prior to diagnosis were compared with the diets of 253 community controls. A quantitative food-frequency questionnaire was used to assess usual dietary intakes of 179 food items. Cases were compared with controls in terms of both the amounts of individual food items consumed and the estimated contributions of 48 nutrients to the diet. Food items consumed more by cases than controls included boiled eggs and omelettes as well as a number of items that could be collectively described as sweet and fatty. Food items consumed less by cases than controls included several vegetables and fruits. Conditional logistic regression analysis of nutrient intake adjusted for total energy and for alcohol and tobacco usage yielded an estimate of relative risk of 3.19, with a 95% confidence interval of 1.58-6.47 for the highest quartile of cholesterol intake (relative to the lowest quartile). For the top quartile of refined sugar intake, the estimated relative risk was 2.21 (95% confidence interval 1.07-4.55). Several nutrients derived principally from plant foods were statistically significantly associated with lower risks. Alcohol consumption was significantly lower among cases than controls. Current smokers had a relative risk of 1.76 (95% confidence interval 0.93-3.34) relative to those who had never smoked. There was no association of pancreatic cancer with coffee drinking. PMID- 1862801 TI - Use of electric blankets and risk of postmenopausal breast cancer. AB - Chronic exposure to 60-Hz electromagnetic fields has been hypothesized to increase breast cancer risk by suppressing the normal nocturnal rise in pineal melatonin. From 1987 to 1989 in western New York the authors investigated the use of electric blankets as a risk factor for breast cancer in a case-control study of postmenopausal women aged 41-85 years. A study population of 382 cases and 439 randomly selected community controls was queried regarding use in the previous 10 years, the frequency of use by season, and the mode of use. After adjusting for age and education, the odds ratio (OR) for use of an electric blanket in the past 10 years (33% of cases, 35% of controls) was 0.89 (95% confidence interval (95% CI) 0.66-1.19), and the risk did not differ in a dose-response fashion by the number of years used. The risk associated with daily use relative to nonuse was 0.97 (95% CI 0.70-1.35). Use sometimes to warm the bed and sometimes throughout the night was not associated with risk (OR = 0.64, 95% CI 0.40-1.05). The risk of breast cancer among those who used the blanket continuously throughout the night was 1.31 (95% CI 0.88-1.95). Those who reported daily use in season, continuously throughout the night for the past 10 years did not have significantly elevated risk (OR = 1.25, 95% CI 0.73-2.16). Adjustment for the Quetelet index and reproductive risk factors did not alter the results. These findings do not support the hypothesis that electric blanket use is associated with an increased risk for breast cancer. The slightly elevated estimate of risk for the most frequent electric blanket users and the potential public health significance of electromagnetic field exposure suggest that further inquiries be undertaken. PMID- 1862802 TI - Pregnancy and gallstone disease: an empiric demonstration of the importance of specification of risk periods. AB - This paper discusses the importance of specification of risk periods in research of the effect of pregnancy on the occurrence of gallstone disease. The authors present data from a case-control study, started in 1983 in Maastricht, The Netherlands. The study comprised 100 acute gallstone cases and 305 general population controls and 41 elective cases and 122 elective radiodiagnosis controls. In a conventional analysis, the rate ratio for one or more pregnancies ever (vs. never) was 1.2 (90% confidence interval 1.02-1.36). In an analysis that discerned several subsequent risk periods, an effect was found only for the risk period up to 5 years after pregnancy (rate ratio, 2.4; 90% confidence interval 1.12-4.96). Beyond this risk period no effect was noted. The results suggest that pregnancy increases the rate of gallstone formation only transiently. Six reasons for specifying risk periods in nonexperimental etiologic studies are discussed. The authors contend that ignoring of risk periods explains part of the variation in the findings of earlier studies on pregnancy and the risk of gallstone disease. PMID- 1862803 TI - Respiratory health effects of home dampness and molds among Canadian children. AB - In 1988, the authors conducted a questionnaire-based study on the health effects of the indoor environment in 30 Canadian communities. This paper focuses on the association between the respiratory health of young children and home dampness and molds. A total of 17,962 parents or guardians of schoolchildren received a questionnaire, and 14,948 (83.2%) questionnaires were returned. Children living in mobile homes, tents, and boats were excluded as were those with cystic fibrosis, leaving 13,495 children included in the study group. The housing stock was distributed as follows: 81% were one-family detached homes, 6% were one family attached homes, and 13% were buildings for two or more families. Molds were reported in 32.4%, flooding in 24.1%, and moisture in 14.1% of the homes. Prevalences of all respiratory symptoms were consistently higher in homes with reported molds or dampness; i.e., adjusted odds ratios ranged from 1.32 (95% confidence interval 1.06-1.39) for bronchitis to 1.89 (95% confidence interval 1.58-2.26) for cough. The prevalence of home dampness or molds, 37.8%, indicates that it is an important public health issue. Further studies are required to elucidate the pathogenesis. PMID- 1862805 TI - Physical activity and depression: evidence from the Alameda County Study. AB - The relation between level of physical activity and risk of subsequent depression was examined using three waves of data from the Alameda County Study. Among subjects who were not depressed at baseline, those who reported a low activity level were at significantly greater risk for depression at the 1974 follow-up than were those who reported high levels of activity at baseline. Adjustments for physical health, socioeconomic status, life events, social supports, and other health habits did not affect the association appreciably. Associations between 1965-1974 changes in activity level and depression in the 1983 follow-up suggest that the risk of depression can be altered by changes in exercise habits, although these associations were not statistically significant after adjustment for covariates. These results provide somewhat stronger evidence for an activity depression link than do previous studies, and they argue for the inclusion of exercise programs as part of community mental health programs, as well as for further studies that focus on the relation between life-style and mental health. PMID- 1862806 TI - Re: "A meta-analysis of physical activity in the prevention of coronary heart disease". PMID- 1862804 TI - Association of indoor nitrogen dioxide with respiratory symptoms and pulmonary function in children. AB - The effect of indoor nitrogen dioxide on the cumulative incidence of respiratory symptoms and pulmonary function level was studied in a cohort of 1,567 white children aged 7-11 years examined in six US cities from 1983 through 1988. Week long measurements of nitrogen dioxide were obtained at three indoor locations over 2 consecutive weeks in both the winter and the summer months. The household annual average nitrogen dioxide concentration was modeled as a continuous variable and as four ordered categories. Multiple logistic regression analysis of symptom reports from a questionnaire administered after indoor monitoring showed that a 15-ppb increase in the household annual nitrogen dioxide mean was associated with an increased cumulative incidence of lower respiratory symptoms (odds ratio (OR) = 1.4, 95% confidence interval (95% Cl) 1.1-1.7). The response variable indicated the report of one or more of the following symptoms: attacks of shortness of breath with wheeze, chronic wheeze, chronic cough, chronic phlegm, or bronchitis. Girls showed a stronger association (OR = 1.7, 95% Cl 1.3 2.2) than did boys (OR = 1.2, 95% Cl 0.9-1.5). An analysis of pulmonary function measurements showed no consistent effect of nitrogen dioxide. These results are consistent with earlier reports based on categorical indicators of household nitrogen dioxide sources and provide a more specific association with nitrogen dioxide as measured in children's homes. PMID- 1862808 TI - Guilt and shame. PMID- 1862807 TI - Fragment from a future history of the science of medicine. PMID- 1862809 TI - Managing full-thickness wounds. PMID- 1862810 TI - Do your gloves fit the task? PMID- 1862811 TI - Transfusion nursing: trends and practices for the '90s. Choosing blood components and equipment. National Blood Resource Education Program's Nursing Education Working Group. PMID- 1862812 TI - Transfusion nursing: trends and practices for the '90s. Autologous transfusion. PMID- 1862813 TI - Transfusion nursing: trends and practices for the '90s. Preventing and managing transfusion reactions. PMID- 1862814 TI - Transfusion nursing: trends and practices for the '90s. Building a safe community blood supply. PMID- 1862815 TI - The postop heart. Case example: embolization after prosthesis implantation. PMID- 1862816 TI - South Central jobfocus. The right nursing climate. PMID- 1862817 TI - Pediatrics jobfocus. A time of growing opportunity and rewards. PMID- 1862818 TI - Pressures grow for AIDS testing; court backs 'patients' rights'. PMID- 1862819 TI - Sensory and semantic factors in recognition memory for odors and graphic stimuli: elderly versus young persons. AB - In four experiments, young (18-26 years, M = 21) and elderly (over 65 years, M = 72) people were compared for recognition memory of (a) graphic stimuli (faces of presidents and vice presidents, engineering symbols, and free forms) and (b) everyday odors. On graphic stimuli, the elderly consistently matched the young, but on odors the performance of the elderly was worse. Their poorer olfactory performance was observed after only 26 s, but became truly marked after 1 hr or more. Somewhere between 1 hr and 2 weeks, their odor performance fell to chance, but their graphic performance remained well above chance. Although the young did forget both graphic and odor materials progressively, their performance always stayed above chance over a 6-month period. Experiments 1 and 2 revealed that the elderly are less sensitive to odors than the young (with thresholds about 10-fold higher), which may explain, in part, their poorer olfactory memory performance. Knowledge that the subjects brought to the tasks by way of familiarity with and ability to name odors and faces played a positive role in recognition memory. Because of this positive role, together with the negative role played by verbal distraction, we conclude that odor recognition memory depends, perhaps heavily, on semantic processing. Impaired semantic processing may result even when odors are simply rendered desaturated, or pastel because of the weakening of olfactory sensitivity with aging. PMID- 1862820 TI - Cognitive advantage in sport: the nature of perceptual structures. AB - To extend and clarify the nature of the perceptual processes used by sport experts to perceive schematic sport information, two experiments used schematic football diagrams that varied in structure (structured vs. unstructured) and complexity (complex vs. easy). The primary objective was to examine and characterize the nature of the perceptual structures (chunks) that are initially encoded, stored, and subsequently retrieved. In Experiment 1, compared with nonexperts, experts recalled larger perceptual structures following the initial stimulus presentation of structured stimuli only, replicating the recall findings of previous research in other skill domains. Experiment 2 used a long-term memory recognition task and a sorting task. Experts had superior recall and recognition of structured stimuli only, along with more discriminating sorting criteria of perceptual structures within long-term memory. This suggests that experts possess a highly refined semantic network or organized, structured schematic information. This research extends and clarifies the similarities between the perceptual processes of experts in sport (i.e., football) and experts in skill domains that require obvious cognitive involvement (i.e., chess). The results are discussed with reference to the perceptual and conceptual chunking hypotheses. It is proposed that sport experts' knowledge of a conceptual category enables them to retrieve elements using a "generate-and-test process." PMID- 1862821 TI - HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection. AB - Monocyte human leukocyte antigen-DR (HLA-DR) expression has correlated closely with clinical outcome in severely injured patients at high risk for infection. Monocytes from 77 asymptomatic volunteers expressed HLA-DR antigen with minimal variability in respect to age, gender, race, time of day or year, or serum alcohol level. Patients who developed infection after elective laparotomy had a significantly lower mean percentage of monocytes expressing HLA-DR antigen and a lower mean fluorescent intensity than uninfected patients (p less than 0.05). Severely infected nonsurgical patients had significantly lower values than normal volunteers (p less than 0.01), and the mean fluorescent intensity of those who died from infection was significantly lower than that of those who survived (p less than 0.05). Patients on immunosuppressive regimens after renal transplantation had levels of HLA-DR expression similar to those of the volunteers. Monocyte HLA-DR expression was found to be a reliable marker of clinical infection and showed remarkable reproducibility within the normal uninfected study population. PMID- 1862822 TI - Detection of clinically suspected deep vein thrombosis using light reflection rheography. AB - Venography is the current standard for the diagnosis of deep vein thrombosis (DVT). Noninvasive tests have differing sensitivity and specificity, are technically demanding, and may be subject to variability in interpretation. Light reflection rheography (LRR) is a noninvasive method utilizing light-emitting diodes and a sensor to measure light reflected from the skin surface. The intensity of reflected light establishes a graphic pattern that indirectly quantifies parameters of venous function by measuring changes in the microcirculation. Seventy-two patients who underwent contrast venography at our institution were also evaluated with LRR. Twenty-four patients were found to have DVT as demonstrated by venography. Of these, 23 also had DVT detected by LRR. No evidence of thrombus was seen in 45 patients studied by venography; in this group, 35 had normal venous emptying indicated by LRR. Using LRR, a sensitivity of 96% was achieved in the evaluation of clinically suspected DVT. This sensitivity is comparable with other noninvasive tests. In addition, LRR is easy to operate, portable, inexpensive, and not technically demanding. Further investigation is needed to confirm these data and further define the role of LRR in the evaluation of clinically suspected DVT. PMID- 1862823 TI - Use of light reflection rheography for diagnosis of axillary or subclavian venous thrombosis. AB - Noninvasive diagnosis of axillary and subclavian venous thrombosis or documentation of the post-thrombotic syndrome using modalities currently in use is not definitive. Light reflection rheography, which is a reflection of venous pressure changes in the extremity as recorded from the subdermal capillary plexus, was used to correctly diagnose axillary or subclavian venous thrombosis in 11 patients. A positive study was confirmed by phlebography in each instance. There were no instances of false-positive results. The methodology is simple, involving testing of the venous outflow from the upper extremity in response to exercise, application of venous congesting pressure, and measurement of the rate of venous outflow when the congesting pressure is released. Normal respiratory variations of an open venous system are also assessed by this noninvasive modality. The tracing obtained is easy to interpret and provides objective evidence of proximal venous occlusion. The test is not operator-dependent and the instrumentation is relatively inexpensive. We believe that light reflection rheography may be an exciting development in the noninvasive diagnosis of axillary or subclavian venous compromise and merits further trials. PMID- 1862824 TI - Abnormal esophageal transit in patients with typical reflux symptoms but normal endoscopic and pH profiles. AB - There is a small, well-known cohort of patients who, despite classic reflux symptoms, have a normal esophageal pH profile and endoscopic picture. The treatment of these patients has proved problematic. In an attempt at determining the pathophysiology of this subgroup, we investigated the esophageal transit, using the radiolabeled solid bolus esophageal egg transit technique, in 58 such patients: 25 males, 33 females, mean age 39.5 years (range: 13 to 65 years). The egg transit was normal in 31 (53.4%) patients. In the remaining 27 (46.6%) patients, the condensed image analysis showed the following specific abnormal transit patterns: "step" delay pattern, demonstrating segmental hold-up in mid- or distal esophagus in 16 (59.3%); nonspecific delay in 6 (22.2%); oscillatory pattern in 3 (11.1%); and total nonclearance during the study period (4 minutes) in 2 (7.4%) patients. The patients with abnormal transit patterns had demographic parameters and symptom scores similar to those found in patients with normal transit. This study shows that almost 50% of patients with reflux symptoms and negative pH and endoscopy have abnormal esophageal transit, and almost two thirds of these patients display segmental transit delay in the lower half of the esophagus. The effect on symptomatology by prokinetic agents in the patient subgroup needs evaluation. PMID- 1862825 TI - Role of renal sympathetic nerve activity in renal failure associated with obstructive jaundice in the rat. AB - The propensity for renal failure associated with obstructive jaundice and liver disease may be related to enhanced vasoconstriction of the renal vascular bed with resultant decreases in renal blood flow. Renal sympathetic nervous activity may be a mediator of this effect. The increased renal production of prostaglandins which has been observed in previous models of bile duct ligation may serve to counterbalance the effects of such vasoconstricting influences. This study was undertaken to assess the effect of bile duct ligation on renal function and prostaglandin production in the rat. Furthermore, this study was designed to determine if renal sympathetic nerve activity contributes to the development of renal failure after bile duct ligation. Sprague-Dawley rats underwent either sham operation (n = 8), bilateral renal denervation (n = 10), bile duct ligation alone (n = 11), or bile duct ligation and bilateral renal denervation (n = 10). Renal function was assessed before and 4 days after operation. Bile duct ligation resulted in a 46% decrease in creatinine clearance (p less than 0.01), a 33% decrease in urinary sodium excretion (p less than 0.01), a twofold increase in urine flow (p less than 0.01), and twofold increases in urinary excretion of PGE2, 6-keto-PGF1 alpha, and thromboxane B2 (p less than 0.01). Renal denervation did not prevent the decreases in creatinine clearance and sodium excretion seen after bile duct ligation and had no effect on the changes in urine flow and prostaglandin excretion. These findings demonstrate that bile duct ligation in the rat results in impaired renal function, accompanied by increases in renal prostaglandin production. In addition, this study indicates that the perturbations in renal function and renal prostaglandin production induced by bile duct ligation are not mediated by renal sympathetic nerve activity. PMID- 1862826 TI - Loop colostomies are totally diverting in adults. AB - Temporary colostomy is a mainstay in the treatment of patients with colon injuries. Common teaching is that loop colostomies are not totally diverting. We performed this study to determine whether loop colostomies are totally diverting. Twenty-three patients presenting for closure of loop colostomies were given barium by mouth. Serial abdominal films were obtained at intervals over 24 hours. Scout films were obtained after bowel preparation to see if flushing the colon could cause passage of barium into distal bowel. We could not demonstrate passage of barium into the distal limb of the colon in any patient studied. This was true even in long-established loop colostomies. Bowel preparation did not cause passage of barium into the distal colon. Loop colostomies constructed over a rod and matured immediately totally divert the fecal stream. Most surgeons would agree that this type of colostomy is more easily and quickly created and closed. Since it fulfills the criteria for fecal diversion, the use of divided colostomies should be abandoned when a loop colostomy can be utilized. PMID- 1862827 TI - A nine-year experience with crossover femoro-femoro-popliteal sequential bypass. AB - Multisegmental arterial occlusive disease may require a combined inflow and outflow procedure for optimal treatment of limb ischemia. Twenty-one patients with unilateral iliac artery stenosis or occlusion and ipsilateral superficial femoral artery occlusion underwent crossover femoro-femoro-popliteal sequential bypass during a 9-year period. Seventeen operations were for limb salvage. Patency rates were determined separately for each segment of the bypass. Primary patency rates for the femoro-femoral segment were 89%, 83%, and 57% at 1, 2, and 5 years, respectively. Primary patency rates for the femoro-popliteal segments were 68%, 62%, and 40% at 1, 2, and 5 years, respectively. Limb salvage rates were 100%, 90%, and 77% at 1, 2, and 5 years, respectively. This experience indicates that femoro-femoro-popliteal bypass is an effective treatment in selected patients with severe ischemia due to combined iliac artery and superficial femoral artery disease. PMID- 1862828 TI - Management of educational change in times of medical reorganization. PMID- 1862829 TI - Laparotomy closure reinforced with buried polyglyconate retention sutures. AB - A method of laparotomy closure using continuous no. 0 polyglycolic acid suture for accurate fascial approximation and buried retention sutures of no. 1 polyglyconate for prolonged wound strength is described. Both security and anatomical precision in fascial closure are achieved without the use of nonabsorbable suture material. This method of laparotomy closure is suitable for patients at high risk for fascial dehiscence. PMID- 1862830 TI - Education about death and dying during surgical residency. PMID- 1862831 TI - Outcome of complex vascular and orthopedic injuries of the lower extremity. AB - Thirty-two patients undergoing limb salvage procedures for complex vascular and orthopedic injuries of the lower extremity were studied in order to identify prognostic indicators for delayed amputation in this select group. A high incidence of nerve (38%), soft tissue (66%), and remote injury (47%) was noted. A comprehensive and integrated approach to vascular, orthopedic, and plastic reconstruction was utilized. Of the 32 patients studied, 1 (3.1%) died as a result of remote injury and sepsis. Amputation was required in 9 patients (28%), while 13 (56%) of the patients with limb salvage showed persistent functional or neurologic deficits. Infection was the most significant factor associated with amputation (p less than 0.0005) and was not avoided by the perioperative use of antibiotics. Delayed amputation resulted in a significant extension of total hospitalization (p less than 0.005). The authors favor an aggressive approach to limb salvage with IIIC injury but recommend early amputation in the presence of significant nerve disruption. An attentive use of tissue debridement, intravenous antibiotics, and early wound coverage is needed to limit infection. PMID- 1862832 TI - Safety of simultaneous aortic reconstruction and renal transplantation. AB - Patients with aortic disease and end-stage renal failure who require both aortic reconstruction and renal transplantation (simultaneously or staged) pose a formidable clinical challenge. Traditionally, the performance of either one of these procedures has been viewed as a relative contraindication to the performance of the other. From 1978 to 1989, eight patients were referred to us with the combination of aortic disease and end-stage renal failure. Seven had aneurysmal disease and one had aorto-iliac occlusive disease. Five patients presented with their diseases sequentially and had two sequential operations, with a mean interval of 4 years between procedures. Three patients presented with their diseases simultaneously and underwent simultaneous aortic reconstruction and living related renal transplantation. All patients were followed up for a mean interval of 4.5 years. By life-table analysis, the 5-year renal graft survival was 100%, the primary aortic graft patency was 82%, and the secondary aortic graft patency was 100%. The only death in this series occurred 11 years after aortic reconstruction and 4 months after a renal transplantation and was due to overwhelming cytomegalovirus sepsis. There were no significant differences between the simultaneous and staged groups in terms of operative mortality, postoperative complications, transplant function, or aortic graft patency. From this experience, we conclude that: (1) patients who present simultaneously with aortic disease and end-stage renal failure can safely undergo simultaneous aortic reconstruction and renal transplantation; (2) patients who present with these two diseases sequentially can undergo a second reconstructive procedure with very low operative morbidity and mortality rates; (3) when these two procedures have been performed sequentially, the second procedure has not significantly altered the 30 day or 5-year results of the first procedure; and (4) the 30-day and 5-year results of each procedure have been excellent regardless of the temporal sequence in which they were performed. PMID- 1862833 TI - Ischemic injury to the spinal cord or lumbosacral plexus after aorto-iliac reconstruction. AB - Between January 1, 1980, and June 30, 1989, 9 patients (6 males and 3 females) developed ischemic injury to the spinal cord or lumbosacral plexus following 3,320 operations on the abdominal aorta (0.3%). The incidence of this complication was 0.1% (2 of 1,901) after elective and 1.4% (3 of 210) after emergency abdominal aortic aneurysm repair, and 0.3% (4 of 1,209) after repair for occlusive disease. Three of the latter had prior clinical evidence of distal embolization. Eight grafts were bifurcated (aorto-iliac:four, aorto-femoral: three, aorto-ilio-femoral:one). One patient underwent extra-anatomic revascularization. Only two patients had supraceliac aortic cross-clamping and one patient underwent exclusion of both internal iliac arteries. Four patients had hypotension. Early mortality was 22% (two of nine). Severe perioperative complications, mostly due to associated visceral and somatic ischemia and sepsis, were present in seven of the nine patients. The extent and type of the neurologic injury correlated with long-term outcome. Patients with ischemic injury of the lumbosacral roots or plexus had better recovery. Attention to the pelvic circulation and the collateral blood supply is important. Use of gentle technique to prevent embolization, avoidance of hypotension and prolonged supraceliac cross clamping, revascularization of at least one internal iliac artery, and the use of heparin may decrease but not eliminate paraplegia. Once this unexpected complication occurs, careful neurologic evaluation should be done to localize the lesion and aid prognosis. PMID- 1862834 TI - Clinical implications of combined hypogastric and profunda femoral artery occlusion. AB - From 1983 to 1990, nine patients with combined hypogastric (HA) and profunda femoral arterial (PFA) occlusive disease presented with five nonhealing hip disarticulations, three nonhealing above-the-knee amputations, perineal necrosis in six patients, buttock necrosis in four patients, visceral ischemia in two patients, and lumbosacral spinal ischemia in one patient. Obviously some patients had more than one regional complication. Five patients died from complications of HA/PFA ischemia. Survivors included two patients who required a hemipelvectomy, one patient who required an axillary-to-hypogastric artery bypass graft for stump salvage, and one patient who survived despite lumbosacral paralysis and complete cystectomy. The 56% mortality and 100% morbidity emphasize the critical significance of combined hypogastric/profunda femoral artery circulatory compromise. Efforts should be made to preserve or re-establish the HA and/or PFA circulation whenever possible. A hemipelvectomy may be required to allow the wounds to finally heal. Furthermore, the certainty of an above-the-knee amputation healing is not present in these patients; therefore, a hemodynamic assessment of the healing potential of an above-the-knee amputation is required. PMID- 1862835 TI - Total excision and extra-anatomic bypass for aortic graft infection. AB - Reports of high mortality and amputation rates following total excision and extra anatomic bypass for aortic graft infection have prompted the use of alternate approaches including local antibiotics, partial resection, in situ revascularization, and graft excision without revascularization. Experience with aortic graft infection was reviewed to establish current morbidity and mortality rates and evaluate our bias in favor of total excision and extra-anatomic bypass. Aortic graft infection was identified in 32 patients, 8 with aortoenteric fistulas. The mean interval between graft placement and infection was 34 months. History of groin exposure (75%) or multiple prior vascular surgery (50%) was common. Clinical signs included fever and/or leukocytosis (23 patients), false aneurysm (9 patients), graft thrombosis (6 patients), groin infection (11 patients), and gastrointestinal hemorrhage (6 patients). Microbiologic data, available in 26 patients, demonstrated gram-positive organisms in 15 patients and gram-negative in 9. Multiple organisms were seen in 11 patients. Patients were treated by partial removal with (8 patients) or without (4 patients) revascularization or total removal with (18 patients) or without (2 patients) revascularization. Revascularization was by an extra-anatomic route, either simultaneous or staged. Overall morbidity/mortality was less in the revascularized groups (p = 0.01), while late complications were seen only after partial removal (p less than 0.01). The best results were found after total excision with revascularization. No patient in this group experienced late infection or amputation during a mean follow-up of 34 months (range: 1 to 168 months). Complications after total excision and extra-anatomic bypass for aortic graft infection are lower than generally appreciated. This approach should remain the standard to which other approaches are compared. PMID- 1862836 TI - Impact of magnetic resonance imaging on the management of diabetic foot infections. AB - This combined retrospective/prospective study evaluated the value of magnetic resonance imaging (MRI) in 18 diabetic patients with apparent foot infections. The goal was to define the impact of MRI on directing the expedient and accurate surgical intervention so important in achieving optimal preservation of limb tissue and function. We found that MRI provides a rapid and reliable means of "viewing" the diabetic foot. Unsuspected or poorly localized abscess cavities can be pinpointed for thorough drainage with minimal exploration. An abscess can be differentiated from cellulitis or osteomyelitis. Moreover, persistent fever following drainage of a foot abscess can be reliably evaluated via MRI, obviating the need for empiric surgical reexploration. This exciting noninvasive imaging technique leads to the most accurate surgical drainage of foot abscesses and, at the same time, can prevent unnecessary surgical exploration of the tenuous diabetic foot. PMID- 1862837 TI - Unilateral aortofemoral bypass: a safe and effective option for the treatment of unilateral limb-threatening ischemia. AB - To determine whether unilateral aortofemoral (AUF) bypass is a safe and effective option for the treatment of unilateral limb-threatening ischemia in patients with aortic or bilateral iliac occlusive disease, we reviewed the results of 42 AUF bypasses performed using polytetrafluoroethylene grafts in patients operated on for limb salvage; 11 (26%) of the patients also underwent femoropopliteal or femorodistal (FP/D) bypasses. The indications for surgery were tissue necrosis or ulceration in 18 (43%) patients and rest pain in 17 (40%) patients. The 5-year primary graft patency and limb salvage rates for AUF bypass were 74% and 84%, respectively. The perioperative mortality rate was 5%. There were no significant differences in the primary graft patency or limb salvage rates in patients who underwent AUF bypass with or without FP/D bypass. Only 3 of 41 (7%) AUF bypass patients required subsequent femorofemoral bypass. We conclude that: (1) AUF bypass is a safe and effective surgical option in patients with unilateral limb threatening ischemia and aortic or bilateral iliac occlusive disease; (2) the routine performance of an aortobifemoral or axillobifemoral bypass in patients with unilateral limb-threatening ischemia may be unnecessary; and (3) AUF bypass facilitates the combined inflow and infrainguinal operations that are frequently required for limb salvage in these patients. PMID- 1862838 TI - Heparin, deep venous thrombosis, and trauma patients. AB - One hundred consecutive patients with multiple trauma, who were admitted to a level I trauma center with an injury severity score of 10 or greater, were studied prospectively. A duplex scan was used to evaluate each patient initially and at set intervals during the hospitalization for the presence of deep vein thrombosis (DVT). The prophylactic regimen for DVT in this study was 5,000 U of subcutaneous heparin every 12 hours. This was used in 50 patients at the discretion of the attending physician, while the remaining 50 patients received no DVT prophylaxis. Fourteen of 50 patients (28%) who were receiving heparin developed DVT, while only 1 patient (2%) of the 50 who did not receive heparin developed DVT. The use of heparin did not provide any significant protection in the susceptible trauma patient. It is believed that those patients with minimal lower extremity injuries, lower injury severity scores, and a shorter period of immobilization do not require any form of DVT prophylaxis. However, those patients at increased risk for DVT are better served with either increased doses of heparin or alternative forms of DVT prophylaxis. PMID- 1862839 TI - Utility of arteriography in penetrating extremity injuries. AB - The role of contrast arteriography in the management of patients with penetrating injuries of the extremities is a subject of active debate. To examine our experience, the charts of patients with penetrating injuries of the extremities were retrospectively reviewed. Data from 82 consecutive patients with 98 wounds over the 5-year period from January 1984 to December 1988 were reviewed. Sixty five arteriograms were obtained to investigate 98 wounds: 8 to localize a clinically apparent wound and 57 because of proximity of the wound or the trajectory of the injuring agent to a major neurovascular bundle. Of the 57 arteriograms obtained because of proximity, 11 identified a vascular injury (19%). Six of these wounds required vascular repair; five patients were treated expectantly. Six of the eight arteriograms obtained for clinical indications were positive (75%), while two were negative (25%). There were no amputations in the study, and all vascular reconstructions were considered successful by clinical and vascular laboratory criteria. One patient died of thoracic injuries; otherwise, all patients were discharged in good condition. Long-term follow-up was not available. In summary, 19% of arteriograms done because of proximity criteria alone identified a clinically occult vascular injury. While only 11% of all proximity arteriograms revealed injuries requiring surgical repair, this rate of significant injury warrants aggressive use of proximity arteriography in a patient population that is prone to poor follow-up. PMID- 1862840 TI - Ambulatory stab evulsion phlebectomy for truncal varicose veins. AB - The management of primary varicose veins is evolving. Recovery time, cost, recurrence rate, and cosmesis are critical determinants. Classic "high ligation" and ankle-to-groin stripping is expensive, results in a long convalescence, and may produce unacceptable scarring and possible permanent nerve injury. This report describes the technique of stab evulsion phlebectomy performed in an outpatient setting. Under loco-regional anesthesia, and after high ligation, existing tributary and trunk varicosities are evulsed with specially designed hooks. The multiple stab incisions, 1.5- to 3-mm long, are closed with adhesive strips. Fifty-six patients, with 69 involved limbs, have been operated on during the past 9 months. Postoperative pain and complications were minimal. Convalescence was eliminated and all patients immediately resumed normal daily activities. Cosmesis was excellent. This technique is based on hemodynamically accurate principles. It effectively removes all varicosities, eliminates the proximal source of reflux, and disconnects potentially outflowing perforators, yet leaves in situ undamaged trunk veins, which may be used as potential vein grafts. PMID- 1862841 TI - Which asymptomatic patients should undergo routine screening carotid duplex scan? AB - The benefits of obtaining a routine screening carotid duplex scan have not been established for patients with peripheral vascular disease but no signs or symptoms of carotid artery disease. We retrospectively reviewed all carotid duplex scans (4,000) performed at our institution between 1985 through 1989 and found for analysis 91 scans in 78 patients who underwent a screening duplex scan because of the presence of peripheral vascular disease. Patients with carotid bruits, abnormal carotid pulses, and focal or nonspecific neurologic symptoms were excluded. Thirty-three percent of these patients had carotid stenosis of 16% to 50%, 14% had carotid stenosis greater than or equal to 50%, and 5% had stenosis greater than or equal to 75%. Individual risk factors for atherosclerosis, including elderly age, coronary artery disease, hypertension, diabetes, smoking, and a recent or past history of cardiac or vascular surgery, did not predict the detection of high-grade carotid stenosis. However, all 11 of the patients with carotid stenosis greater than or equal to 50% were 68 years of age and older, and this age range, in combination with the various risk factors, increased the incidence of significant carotid artery stenosis (greater than or equal to 50%) to as high as 45%. We conclude that routine screening carotid duplex scan is indicated in elderly patients (age greater than or equal to 68 years) with peripheral vascular disease, even in the absence of any signs or symptoms of carotid artery disease, when other atherosclerotic risk factors are present. PMID- 1862842 TI - Stump pressure, the contralateral carotid artery, and electroencephalographic changes. AB - Electroencephalographic (EEG) monitoring and measurement of stump pressure are the most widely employed methods of assessing the risk of cerebral ischemia during carotid endarterectomy. The status of the contralateral carotid artery has also been thought to influence the need for placing a shunt. The relationship of EEG monitoring, stump pressure, and the contralateral carotid artery has not been completely delineated. We retrospectively reviewed these three variables in 113 patients undergoing 124 carotid endarterectomies. The contralateral artery was classified as occluded, stenotic (greater than 50% decrease in diameter), or nonstenotic. There was a 48% incidence of EEG changes with contralateral occlusion, 18% with stenosis, and 21% with nonstenotic arteries (p = 0.014). There was a 73% incidence of EEG changes when the stump pressure was less than 25 mm Hg, 32% when the stump pressure was 25 to 50 mm Hg, and 2% when the stump pressure was greater than 50 mm Hg (p less than 0.001). There was no significant difference in the mean stump pressure for patients with occlusion (43.8 mm Hg), stenosis (44.7 mm Hg), or nonstenotic contralateral arteries (51.3 mm Hg). All patients with contralateral occlusion and a stump pressure less than 25 mm Hg had EEG changes. No patient with a stump pressure greater than 50 mm Hg and a patent contralateral artery had EEG changes. Although the incidence of EEG changes in the majority of patients was not accurately predicted by the stump pressure and the status of the contralateral carotid artery, stump pressure less than or equal to 50 mm Hg was sensitive, identifying 97% of patients with EEG changes. PMID- 1862843 TI - Impact of changing attitudes in carotid surgery on community hospital practice. AB - In 1985, institutional guidelines for the evaluation and performance of carotid surgery were established in our community hospital. During the 5-year period from 1985 through 1989, 159 carotid reconstructions were done. There were four major strokes (3%), one eventually resulting in death, with the second death in this series from a myocardial infarction (mortality 1%). The combined mortality/major stroke morbidity incidence was 3%. Three transient ischemic attacks (2%) postoperatively cleared promptly without residua. During the latter 1980s, an increasing number of vascular surgeons were doing less carotid surgery. Monitoring institutional quality assurance and individual surgeon performance within the community hospital is becoming a reality. Our experience with institutional guidelines for the evaluation and conduct of carotid surgery, together with an assessment of results and ongoing individual surgeon performance, is presented. Maintaining acceptable morbidity and mortality statistics can be enhanced by having a plan for assessment, management, and concurrent review. PMID- 1862844 TI - Endarterectomy: the beginning of modern vascular surgery. PMID- 1862845 TI - [The use of a gonadotropin-releasing hormone agonist for treating gynecological diseases]. PMID- 1862846 TI - [Current aspects of the diagnosis of the sclerocystic ovary syndrome]. PMID- 1862847 TI - [Methodological approaches to an analysis of maternal mortality]. PMID- 1862848 TI - [The adult respiratory distress syndrome in eclampsia and eclamptic coma. The diagnostic problems]. PMID- 1862849 TI - [The determination of specific proteins in the biological fluids from pregnant women suffering from diabetes mellitus]. AB - An immunochemistry analyser has been used in testing a series of specific proteins (complement components C3 and C4, properdin, factor B, immunoglobulins G, M and A, alpha 1-antitrypsin, alpha 1-acid protein and alpha 2-macroglobulin) in biological fluids of normal and diabetic women in third-trimester pregnancy. Significant abnormalities in the protein spectrum were found in diabetes mellitus, a marker to be used in monitoring of diabetic pregnancies and control of therapy. PMID- 1862850 TI - [The role of prostaglandins in the development of associated late pregnancy toxicosis in hypertension patients]. AB - The plasma levels of prostaglandins A, E, and F2 alpha were measured by the radioimmunoassay in 146 hypertensive and 62 healthy pregnant females. It was ascertained that beginning in the second trimester, the ratio of various prostaglandins is impaired in the direction of increasing values of substances from the pressor group as the hypertensive disease evolves. This is due to lower levels of prostaglandins A and E and/or higher levels of prostaglandins F2 alpha. In associated late gestosis, prostaglandin levels are related to the clinical manifestations of this disease. There are increased prostaglandin F2 alpha concentrations with severe nephropathy. The studies indicate that prostaglandins affect the course of hypertensive disease in pregnant women and the development of associated late gestosis. PMID- 1862851 TI - [Reflex analgesia in the combined treatment of pregnant women with a pathological preliminary period]. AB - The impact of reflex analgesia via transcutaneous electrical neurostimulation and electrical acupuncture was studied in 46 patients with an abnormal preliminary period by using tests of pain sensations and personal and reactive anxiety, ECG, hysterography, and computer-aided prediction of labor complications. Reflex analgesia was found to contribute to effective abolishment of preliminary pain sensations, to normalization of central nervous system function, autonomic reactions, uterine contractility, to reduction in pharmacological agent use and treatment duration, and to better delivery. PMID- 1862852 TI - [The content of sex steroid hormones in the blood of healthy and anemic parturients and in the umbilical vessels of their newborn infants]. AB - The investigation of the venous blood from 62 healthy and anemic parturients and the umbilical vascular blood from their newborns has indicated that lower steroidogenic activity in the fetus was directly related to its maternal disease severity. The synthesis of dehydroepiandrosterone sulfate and the metabolism of progesterone, estrone, and estradiol are affected. The placental transfer of progesterone, estrone, estradiol, and total estriol is also decreased. Endocrine activity in the placenta drastically drops with severe anemia. PMID- 1862853 TI - [The characteristics of the clinical picture and treatment of patients with acute kidney failure in obstetrical pathology]. AB - The examination of 45 patients with acute renal failure (ARF) caused by obstetric problems identified 3 types of its clinical course: 1) "pure" ARF; 2) ARF in the presence of sepsis, and 3) ARF in the presence of exogenous intoxication. Types 2 and 3 were more severe and showed higher mortality rates. The average number of hemodialysis sessions per patient was 2.4, 3.6, and 9.8 with types 1, 2, and 3, respectively. The treatment was of multimodality, including suppurative focus debridement, therapeutic measures, hemodialysis, and hyperbaric oxygenation; with types 2 and 3 efforts were made to combat sepsis, hemodynamic and coagulative abnormalities, multiorgan failure. The operative risk during evolved ARF is extremely high; uterine curettage, rational bacterial therapy, refusal of nephrotoxic agents are preferred. Better treatment outcomes were due to a session of 5-10 hyperbaric oxygenation procedures which were performed in anaerobic sepsis, pulmonary edema, arterial hypoxemia. The patients who had received hyperbaric oxygenation had less severe ARF, lower incidence of complications and lower mortality rates, they tolerated hemodialysis better. PMID- 1862854 TI - [Decreasing perinatal morbidity and mortality in incomplete pregnancy]. PMID- 1862855 TI - [The potentials for using Tl201 chloride in the differential diagnosis of coronarogenic and noncoronarogenic myocardial lesions in women in the climacteric]. PMID- 1862856 TI - [Hyperplastic processes in the target organs of women over 35 who have undergone an operation for the wedge resection of polycystic ovaries]. PMID- 1862857 TI - [Tissue and plasma hemostasis in inflammatory diseases of the uterus and adnexa (a discussion of the article by G. M. Savel'eva and L. V. Antonova)]. PMID- 1862859 TI - [The principles of the outpatient polyclinic diagnosis and treatment of gynecological endocrine diseases]. PMID- 1862858 TI - [Tubo-ovarian inflammatory formations: the nosological and therapeutic aspects of the problem]. PMID- 1862860 TI - [The "list of complaints" of the Clinic for Female Diseases of Moscow University (the end of the 19th-the beginning of the 20th centuries)]. PMID- 1862861 TI - [The current approaches to choosing a rational procedure for the pregnancy and labor management of women with a scar on the uterus]. PMID- 1862862 TI - [Serum oxytocin and oxytocinase activities in women during pregnancy]. AB - Serum oxytocic and oxytocinase activities were examined in 50 females with normal pregnancy and 50 with threatened abortion by using biological (oxytocin) and biochemical (oxytocinase) methods. The findings suggest that there is no regular changes in serum oxytocic activity in the course of pregnancy, whereas its oxytocinase activity significantly increases with pregnancy development. The females with threatened abortion showed the same values of serum oxytocic activity as those with normal pregnancy, but much lower oxytocinase activity. The assay of serum oxytocinase activity may be of diagnostic value when threatened abortion is suspected. PMID- 1862863 TI - [Clinical significance of factors affecting the course of pregnancy and the status of newborn infants born to women with uterine scar]. AB - Clinical, ultrasonic (fetoscopy, placentography, Doppler metry of uteroplacental and fetoplacental blood flow), and radioimmunological methods (measurement of follicle-stimulating and luteinizing hormones, estradiol, estriol, progesterone) were used to examine 98 pregnant with a cicatrix onto the uterus. The early neonatal period was studied thoroughly in some newborns. The acid-base balance, umbilical vascular blood gases, arterial blood oxygen saturation, heart rate, blood pressure, and body temperature were measured. Having no clear-cut negative action on the uteroplacental and fetoplacental blood flow, an inadequate cicatrix was found to be a risk factor for fetal hypotrophy. Due to lower adaptative possibilities, the newborns to mothers having a cicatrix onto the uterus should constitute a risk group for complications in the neonatal period. It is concluded that repeated elective cesarean section performed in the period close to delivery is one of the factors that lower perinatal mortality and morbidity of babies born to mothers with a cicatrix on the uterus. PMID- 1862864 TI - [Pharmacological protection of pregnant women with heart defects during abdominal delivery]. AB - The drug salvage developed by the authors was studied for its impact on maternal, fetal, neonatal homeostasis, the incidence of unfavourable outcomes in the mother and her fetus in 40 pregnant with cardiac malformations whose pregnancy was delivered via cesarean section as a planned operation. The baseline hypodynamic circulation was detected in pregnant with heart disease. This was found to be steady-state during the operation and the drug salvage was adequate in the females. This showed a 2.7- or 2.0-fold reduction in maternal cardiovascular events and unfavourable neonatal sequelae, respectively. PMID- 1862865 TI - [Risk factors and causes of abortion]. PMID- 1862866 TI - [Endometrial steroid receptor levels in habitual abortion in advanced pregnancy]. AB - Estrogen and progesterone reception was examined in the endometrial cytoplasmic and nuclear fraction from apparently healthy subjects and patients with habitual late incompetent pregnancy in the early proliferative and late secretory periods of a menstrual cycle. The reception of the two reproductive hormones in the nuclei and the binding of estrogens in the endometrial cytosol were demonstrated to be significantly higher in the female patients than in healthy subjects. The cytosol estrogen to progesterone reception ratio was increased in the patients in the secretory phase of a menstrual cycle than in normal females. There was a complete normalization of endometrial reproductive hormone receptor levels in the patients undergoing hyperbaric oxygenation. PMID- 1862867 TI - [Activity of natural killer cells in various forms of abortion]. AB - The activity of natural killer (NK) cells was found to be significantly higher in females with various miscarriages than that in those with normal pregnancy. The highest NK cell activity was observed in females with interrupted pregnancy. PMID- 1862868 TI - [Contractile activity of the uterus in different variants of cervix dilatation and fetal forward movement during labor]. AB - The biomechanism of labour pains was examined by analysing the amplitude, frequency, and duration of the pains during labours accompanied by arrests in the course of cervical dilatation and fetal forward movement. The forces driving out the fetus from the uterus were shown to be formed of two components: 1) uterine wall muscular layer tension and 2) amniotic fluid hydraulic pressure, the former being of greater importance than the latter. PMID- 1862869 TI - [Cesarean section in pre-term pregnancy]. PMID- 1862870 TI - [Experience with conducting programmed labor]. AB - An analysis was made of programmed labours in 128 high-risk females having relative indications for cesarean section. Oxytocin or prostaglandin was used as a uterine-contracting agents. The dosage, rate and duration of drug administration were adjusted by the values of uterine activity and the rate of cervical dilatation. In the latent phase (up to 4-5 cm) the optimal dilatation rate was considered to be 1 cm/h in primiparas, 1.5 cm/h in multiparas; in the active period (over 5 cm), that was 1.5 and 2.0 cm/h, respectively. The optimal labour duration was at least 10-12 hours in primiparas and at least 8 hours in multiparas. One hundred and sixteen (90.6%) females delivered vaginally without any delivery operations. Twelve (9.4%) delivered via cesarean section. All 128 babies were liveborn. It has been concluded that programmed labour is a sparing tool of delivery in high-risk pregnant who have no indications for cesarean section. PMID- 1862871 TI - [Epidural anesthesia in cesarean section]. PMID- 1862872 TI - [Diagnostic value of Doppler ultrasonography in the evaluation of the status of uterine blood flow in puerperium]. AB - A study of 118 puerperants+ revealed that Doppler metry objectively evaluated the artery blood flow in the postpartum uterus. There was a progressive increase in uterine vascular resistance in the uncomplicated postpartum period following spontaneous labour, whereas there was a reduction in peripheral resistance in the endometritis-complicated period, which caused a rise in the end-diastolic blood flow. Postpartum uterine blood flow following cesarean section displayed low peripheral resistance in the presence or absence of an inflammatory process. PMID- 1862874 TI - [The examination system and the stages of restorative treatment of women after microsurgical reconstructive operations in tubal- peritoneal infertility]. PMID- 1862873 TI - [Correction with T-activin of secondary immunodeficiency in inflammatory diseases of female internal genital organs]. AB - A clinicoimmunological examination was performed in 70 patients with acute inflammatory disease of internal genitalia. All the patients received a multimodality anti-inflammatory therapy. They were divided into 2 groups: 1) 30 patients taking ++T-activin as an adjuvant and 2) 40 patients untreated with it. T and B lymphocytes were measured by current cytofluorometry+ by means of monoclonal antibodies and the rosette-forming method. A subpopulation analysis of the T-cell immune system revealed lower T-helper count and decreased immunoregulatory index. ++T-activin used in the multimodality therapy for acute inflammatory diseases of internal genitalia improved the qualitative parameters of regulatory T-cell subpopulations, returned T and B lymphocytes to normal levels and elevated IgG concentrations. PMID- 1862875 TI - [Informative value of various biochemical parameters of homeostasis in the formation of endometrial cancer risk groups]. AB - A total of 97 patients suffering from endometrial polyposis, hyperplasia, adenomatous hyperplasia, and carcinoma were examined. The levels of malonic dialdehyde as an index of lipid peroxidation, average-mass molecules, C peptide, humoral immunity parameters were studied. The content of circulating immune complexes were also determined. Specific changes which might be an auxiliary factor in predicting the therapy and forming cancer risk groups were identified. PMID- 1862877 TI - [Effect of hypotensive drugs on the metabolism of placental proteins]. PMID- 1862876 TI - [Intrauterine contraception in nulliparous women]. PMID- 1862878 TI - [Perinatal pathology in the offspring of women treated for endocrine infertility and the ways of its correction]. PMID- 1862880 TI - [Cryotherapy in the treatment of benign diseases of the cervix uteri]. PMID- 1862879 TI - [Consultation regarding the problems of contraception in Finland]. PMID- 1862882 TI - [30-year-old lithopedion associated with ovarian cyst and large umbilical hernia]. PMID- 1862881 TI - [Sequelae of unilateral ovariectomy in women of reproductive age]. PMID- 1862883 TI - [Renal dystopia and genital pathology]. PMID- 1862884 TI - [Specific diagnosis and conservative therapy of acute inflammatory adnexal diseases]. PMID- 1862885 TI - [Anatomic and clinical narrow pelvis]. PMID- 1862886 TI - [Hysteroscopy in operative gynecology]. PMID- 1862887 TI - The pill, HRT and postoperative thromboembolism: cause for concern? PMID- 1862888 TI - Cost of intensive therapy. A description of methodology and initial results. AB - A preliminary study was performed to calculate the cost of intensive therapy on an individual patient basis. The fixed (equipment, supporting services and land opportunity), semi-fixed (staff) and marginal (treatment) costs of 20 critically ill patients were calculated individually. The results show that there is wide variation in intensive therapy costs. The average daily cost for a spontaneously breathing patient was 399 pounds (95% confidence intervals 388 pounds-460 pounds) while that for a ventilated patient was 726 pounds (656 pounds-795 pounds). The mean total cost per patient was 1980 pounds, but the cost per survivor increased by 16% (347 pounds) because of four deaths on the intensive care unit. High total costs are associated with increased severity of illness and higher marginal (treatment) costs are associated with increased semi-fixed (staff) costs. The cost of intensive therapy was three to five times that for general ward care. PMID- 1862889 TI - Immunological disturbances in anaesthetic personnel chronically exposed to high occupational concentrations of nitrous oxide and halothane. AB - Immunological changes in anaesthetic personnel exposed to occupational concentrations of holothane and nitrous oxide 10-60 times greater than the advised maximum were studied during routine work and after 3-4 weeks holiday. Red cell count, haemoglobin concentration and haematocrit decreased during exposure although not significantly, in comparison with a control group, but all had increased significantly after the holidays. Other changes were altered neutrophils and lymphocyte counts. Basophils disappeared from the blood during the exposure. Monocytes were not affected during the exposure, but increased after its cessation. Percentages of CD2 and CD4 lymphocytes increased significantly, but numbers of cells in T lymphocyte subpopulations (total, helper and cytotoxic/suppressor lymphocytes) were not significantly altered. B lymphocytes were most strongly affected: they decreased during working periods and did not recover after holidays. Natural killer (NK) cells, on the other hand, decreased significantly during exposure, but fully recovered during holidays. After stimulation with mitogens, phytohaemaglutin, concanavalin A, and pokeweed, lymphocytes from exposed personnel incorporated significantly more 3H-thymidine than those from control subjects, but stimulation indices did not differ. The natural killer-cell activity, serum Ig concentrations and phagocytosis by granulocytes were not altered. PMID- 1862890 TI - Morphine compared with diamorphine. A comparison of dose requirements and side effects after hip surgery. AB - The dose requirements and side effects of morphine were compared with those of diamorphine administered by patient-controlled analgesia in 40 patients following elective total hip replacement. Patients were allocated randomly to receive in a double-blind manner either morphine or diamorphine for postoperative pain relief. There were no significant differences between the two groups with regard to postoperative sedation, nausea, well-being, pain relief and requirements for antiemetic drugs. The dose requirement for diamorphine was approximately 50% of that for morphine. PMID- 1862891 TI - A double-blind study of the speed of onset of analgesia following intramuscular administration of ketorolac tromethamine in comparison to intramuscular morphine and placebo. AB - A double-blind, randomised, parallel group, placebo-controlled study was performed in 85 patients to compare the speed of onset of analgesia following the intramuscular administration of a single dose of 30 mg of ketorolac tromethamine, 10 mg of morphine or placebo. A new, sensitive, method was used to measure the latency of analgesia. The onset of analgesia was defined by the time taken for the pain intensity score to reach a specified percentage of the baseline value. Twenty-five percent of patients achieving a 50% reduction in baseline pain intensity score appears to be the most appropriate parameter to assess the speed of onset of analgesia of ketorolac and morphine in the postoperative setting. Paired comparison demonstrated that ketorolac had a significantly faster onset of analgesia (p = 0.03) when compared to placebo, whilst comparison of morphine to placebo analgesic latency (p = 0.06) just failed to reach significance. There was no significant difference between the analgesic onset time of ketorolac and morphine (p = 0.73). Intramuscular ketorolac and intramuscular morphine have comparable analgesic onset times in the postoperative pain context. However, the sensitive method of measuring onset of analgesia described, highlights the slow onset of analgesia when analgesics of known efficacy are given by the intramuscular route in the postoperative period. More attention should be given to the speed of onset of analgesia in future assessments of analgesics. PMID- 1862892 TI - Intubation through the laryngeal mask. A technique for unexpected difficult intubation. AB - Unexpected difficulty with tracheal intubation contributes to anaesthetic mortality. The laryngeal mask can almost always be placed satisfactorily and its position should facilitate blind intubation. A 6-mm cuffed tube will pass through both adult sizes of the mask and this study tested the feasibility of intubation through the mask. The effect of the application of cricoid pressure on the technique was also investigated. Intubation via the laryngeal mask was attempted in 100 routine patients: of the first 50 (group 1, no cricoid pressure), 45 (90%) were successfully intubated. Maintenance of cricoid pressure throughout the manoeuvre (group 2) reduced the success rate significantly to 56% (p less than 0.05). Despite the possibility that cricoid pressure may have to be interrupted momentarily, the ease with which the technique can be learnt, and the immediate availability of the necessary apparatus suggest that it should be considered for inclusion in failed intubation drill. PMID- 1862893 TI - Epidural bupivacaine dilution for labour. A comparison of three concentrations infused with a fixed dose of fentanyl. AB - We have compared the effects of three epidural infusions in a randomised, double blind study of 56 primigravid mothers in labour. An initial dose of bupivacaine 0.5% 8 ml was followed by infusion of either bupivacaine 0.125%, 0.062% or 0.031%. All solutions contained fentanyl 0.0002% and were run at 7.5 ml/hour. Women receiving the most dilute solution had significantly less analgesia (p less than 0.001) for the first 4 hours of the study, but pain scores were then similar for the three groups. No obvious benefit was gained by using very dilute bupivacaine. PMID- 1862894 TI - Intra-operative patient-controlled sedation. Comparison of patient-controlled propofol with anaesthetist-administered midazolam and fentanyl. AB - The quality of sedation and postoperative recovery have been assessed for intra operative sedation provided by either patient-controlled sedation with propofol or a standard method using divided doses of midazolam and fentanyl, in 40 ASA 1 day surgery patients undergoing extraction of third molar teeth under local analgesia. Patient-controlled sedation with propofol produced sedation no deeper than full eyelid closure with prompt response to verbal command, but deeper levels were seen in three patients in the midazolam and fentanyl group. Patient satisfaction was higher in the patient-controlled sedation propofol group for both subjective intra-operative feelings (p less than 0.01) and willingness to have the procedure again in the same manner (p less than 0.05). Amnesia was more limited to intra-operative events (rather than extending into the postoperative period) in the patient-controlled sedation propofol group (p less than 0.05). Drug dose was correlated with duration of procedure and surgical difficulty in the patient-controlled sedation propofol group but not in the midazolam and fentanyl group. Postoperative testing included a new computerised test, the FAST index, which indicated a dose-dependent reduction in cognitive function in the midazolam and fentanyl group, which persisted until the time of discharge. Changes in cognitive function in the patient-controlled sedation propofol group in the same postoperative interval were significantly less and not related to propofol dose. PMID- 1862895 TI - Fatal theophylline poisoning with rhabdomyolysis. A potential role for dantrolene treatment. AB - A fatal case of theophylline poisoning is described. The patient developed rhabdomyolysis, renal failure and compartment syndrome, as well as the more usual features of severe theophylline poisoning. Dantrolene appeared to be useful in controlling the hypermetabolic state associated with the overdose and may have a role in future treatment. PMID- 1862896 TI - Epidural analgesia in Eaton-Lambert myasthenic syndrome. Effects on respiratory function. AB - The anaesthetic management of a patient with Eaton-Lambert myasthenic syndrome undergoing thoracotomy is described. Epidural anaesthesia, in combination with a light level of general anaesthesia, provided good operating conditions and postoperative analgesia. Pulmonary function and ventilatory responses to carbon dioxide and hypoxia were measured before operation. These tests were repeated after the epidural administration of 8 ml 2% lignocaine before surgery and after 2 mg morphine sulphate in 10 ml saline postoperatively. Minor reductions in some of the ventilatory parameters were observed. The epidural technique appears to be a useful and safe method by which to manage patients with Eaton-Lambert syndrome undergoing thoracotomy. PMID- 1862897 TI - Chemical meningism after lumbar facet joint block with local anaesthetic and steroids. AB - A case is reported in which chemical meningism occurred after lumbar facet joint block with methylprednisolone acetate and bupivacaine. This complication was probably due to inadvertent dural puncture. The use of steroids in facet joint injections is questioned. PMID- 1862898 TI - Tracheal tube resistance and airway and alveolar pressures during mechanical ventilation in the neonate. AB - The relationship between peak airway pressure, alveolar pressure and respiratory frequency was calculated for the range of compliances and airway resistances which might be encountered during mechanical ventilation of a 3-kg neonate. The pressure/flow relationships of 2.5, 3.0, 3.5 and 4-mm tracheal tubes were determined at a series of flows from 0.5 to 4 litres/minute. Peak airway and alveolar pressures were then measured at various frequencies and inspiratory:expiratory ratios with the tubes incorporated in a model lung. Large differences between peak airway and alveolar pressures developed when frequency was increased or inspiratory time decreased; the differences were greatest with the smaller tubes. Shortening expiratory time by increasing the frequency or altering the inspiratory:expiratory ratio resulted in increased end-expiratory pressure because of incomplete emptying of the lung. PMID- 1862899 TI - Percutaneous dilational tracheostomy. A bedside procedure on the intensive care unit. AB - Tracheostomy is performed commonly to aid weaning from assisted ventilation in patients who require intensive care. The procedure carries a significant mortality and morbidity, in part due to problems in moving unstable patients. We report the use of a bedside percutaneous tracheostomy technique for use in adult patients who require intensive care. The procedure was successful in 19 of 20 cases. The one failure, in the first case, resulted from transection of a superficial midline vein. The lack of significant haemorrhage was notable in all other cases. The procedure has proved to be efficient and cost-effective in this unit and has now replaced conventional surgical tracheostomy in this group of patients. PMID- 1862900 TI - The effect of micropore filters on the aspiration test in epidural analgesia. AB - Continuous epidural analgesia may be complicated by intravascular or subarachnoid injection of local analgesic, with disastrous consequences. One of the techniques described to prevent these complications is the aspiration test. It is the current standard of practice to employ a micropore bacterial filter for epidural infusions. We present an in vitro study of nine commercially available bacterial filters to determine whether or not the aspiration test could be reliably performed through them. Eight of the nine filters (except the Perifix, Braun) were found to be unreliable if air and liquid were both present in the system (air lock). The role of the aspiration test and the use of micropore filters in epidural analgesia are discussed, as are the implications and possible solutions in practice of this cause of failure of the test. PMID- 1862902 TI - Assessing intravenous cannulation and tracheal intubation training. AB - A simple graphical method is described that allows the assessment of a student's progress while learning intravenous cannulation and tracheal intubation. Thirty four students were studied during their initial training; 91% of those students who obtained a sufficient number of trials to allow a final assessment to be made met the criterion of 80% success for cannulation and 95% achieved similar success in intubation. Thirty-one ambulance staff who returned for a 3-day refresher course were also assessed; 44% (for intravenous cannulation) and 61% (for tracheal intubation) met the 80% success criterion. PMID- 1862901 TI - Clinical evaluation of a spinal catheter technique in femoro-popliteal graft surgery. AB - The use of a 24-gauge catheter for continuous spinal anaesthesia was evaluated in 20 patients undergoing femoro-popliteal graft surgery for occlusive disease. The catheter was inserted through either a Tuohy or Quincke-tip needle and isobaric amethocaine used for the initial injection. In five patients identification of the subarachnoid space was not straightforward, but clear difficulty with catheter insertion was encountered in only one. The range of blocks seen was wider than expected, but it was adequate for surgery 15 minutes after injection in 16 of the 20 patients. In another three the injection of a small dose of hyperbaric bupivacaine produced the necessary extension of block. Two patients (10%) required a general anaesthetic, one because of grossly inadequate spread of solution, the other because the catheter kinked and prevented injection of a second dose after the start of surgery. PMID- 1862903 TI - Nausea and vomiting with use of a patient-controlled analgesia system. AB - The incidence of nausea and vomiting following patient controlled analgesia and intramuscular morphine injections on demand was compared in a double-blind randomised study of 32 healthy patients undergoing elective cholecystectomy. There were no significant differences between the two groups in mean 24 hour postoperative morphine consumption, subjective experience of pain, nausea and sedation assessed by visual linear analogue scoring, and the postoperative requirements for antiemetic therapy. PMID- 1862904 TI - Incidence and management of airway problems in the CHARGE Association. AB - The airway problems associated with anaesthesia in patients with the CHARGE Association have been underreported. We undertook a retrospective review of 50 cases, of which anaesthetic records were available for 37 patients. Apart from choanal atresia and cleft lip and palate, 56% of patients has some other upper airway abnormality. There appeared to be greater difficulty in tracheal intubation with increase in age in four patients. The incidence and management of airway abnormalities are discussed. PMID- 1862905 TI - Extradural vein puncture--an avoidable complication. AB - Accidental cannulation of an extradural vein is a troublesome and potentially serious complication of extradural catheter insertion. This study was conducted to assess the influence of posture, catheter size and the injection of saline before catheter insertion, on its occurrence. Eight different techniques were studied based on combinations of these three factors. There was no difference in incidence with respect to posture. The use of 18-gauge catheters, after injection of 10 ml of 0.9% saline, resulted in a significant (p less than 0.01) reduction in the incidence of extradural vein cannulation. This technique is recommended in obstetric patients as a means of avoiding accidental intravenous injection of local analgesic. PMID- 1862906 TI - Attenuation of suxamethonium myalgias. PMID- 1862907 TI - Trauma to the posterior pharyngeal wall caused by a laryngeal mask airway. PMID- 1862908 TI - Laryngeal mask airway in children: insertion technique. PMID- 1862909 TI - Laryngeal masks and chair dental anaesthesia. PMID- 1862910 TI - Yet another use for the laryngeal mask airway. PMID- 1862911 TI - Unexpected position of the laryngeal mask airway. PMID- 1862912 TI - Malfunctioning of disposable breathing systems. PMID- 1862913 TI - Cuff failure--a complication of tracheal intubation. PMID- 1862914 TI - Precordial stethoscopes. PMID- 1862915 TI - Guide wire embolism. PMID- 1862916 TI - Upper airway obstruction by enlarged tonsils. PMID- 1862917 TI - Coagulation screening before epidural analgesia in pre-eclampsia. PMID- 1862918 TI - Ethyl chloride and diethyl ether for assessing the extent of epidural blockade. PMID- 1862919 TI - Assessment of training in anaesthesia and related skills. PMID- 1862920 TI - Block of epidural needle by blood clots. PMID- 1862921 TI - Blood clot obstruction of the upper airway. PMID- 1862922 TI - 32-gauge spinal catheters through 26-gauge needles. PMID- 1862924 TI - Fixation of nasotracheal and nasogastric tubes. PMID- 1862923 TI - Suxamethonium in a cannula deadspace--a danger. PMID- 1862925 TI - Pulmonary artery catheter entrapment. PMID- 1862926 TI - Central venous cannulation: a complication. PMID- 1862927 TI - Freezing of thiopentone solution. PMID- 1862928 TI - The anaesthetic management of tracheal stenosis. PMID- 1862929 TI - The Annual Conference of Linkmen of the Association of Anaesthetists of Great Britain and Ireland, 1990. PMID- 1862930 TI - Dealkylation of 7-methoxycoumarin as assay for measuring constitutive and phenobarbital-inducible cytochrome P450s. AB - Six alkyl ethers of 7-hydroxycoumarin, ranging from methoxy- to hexoxycoumarin, were studied for their NADPH-dependent metabolism by liver microsomes of male rats treated with phenobarbital (PB) or 3-methyl-cholanthrene (MC). The six alkyl ethers were metabolized by both types of microsomes, forming 7-hydroxycoumarin as the major product. Among the test compounds, 7-methoxycoumarin was unusual in that its dealkylation was inducible only by PB and not by MC. PB increased 7 methoxycoumarin-O-demethylase (MOCD) activity about four- to eightfold. Metyrapone strongly inhibited MOCD in PB-treated microsomes but not in MC-treated microsomes. Similarly, monoclonal antibodies directed toward PB-induced cytochrome P450s selectively suppressed MOCD in PB-treated microsomes. MOCD activity was observed in preparations of SD1 cells containing only cytochrome P450IIB1, while it was not found in preparations of XEM1 cells containing only cytochrome P450IA1. Demethylation of 7-methoxycoumarin was also mediated by the constitutive cytochrome P450 form(s) of liver, lung, small intestine, and kidney (in decreasing order). PB increased MOCD activity of small intestine by 40% but was without effect on the dealkylation activity of lung and kidney. MOCD activity was also detectable in differentiated rat hepatoma lines H4IIEC3 and 2sFou. The studies indicate that dealkylation of 7-methoxycoumarin is a highly sensitive, simple, and practical assay for estimating constitutive and PB-inducible cytochrome P450-dependent monooxygenase activities. PMID- 1862931 TI - Apparatus for gel electrophoresis with continuous monitoring of individual DNA molecules by video epifluorescence microscopy. AB - Apparatus for gel electrophoresis with continuous scanning by video epifluorescence microscopy was constructed and applied to measurements on individual DNA molecules in the size range of several hundred kilobase pairs. The gel electrophoresis apparatus comprises a horizontal glass cell and several commercially available components--an epifluorescence microscope, an image intensifier, two video cameras, a monitor, videotape recorder and voltmeter. Data in the form of videotapes can be subsequently analyzed on a computer graphics work station. PMID- 1862932 TI - A laser densitometer for selective spot analysis on dot blots and two-dimensional gel autoradiograms. AB - We describe an inexpensive densitometer, employing a small HeNe laser and an IBM compatible personal computer that performs accurate measurements of selected spots on two-dimensional gel autoradiograms or chromatograms with an accuracy and a sensitivity equal or superior to those of many commercial instruments. Our open table design allows the operator to visually monitor the scanning process in room lighting, and provides great flexibility in both the size and the nature of items to be scanned. The instrument has two moving parts (a prism and a small motor). A commercially available software package (ASYST) acquires digital data, graphs the data on the TV monitor, converts the data to optical density or to radioactive incorporation (cpm), subtracts background, integrates peak areas, and stores data on disk. The total time for these operations is 20-30 s per spot. The instrument has a dynamic range of 0.25 to 3.0 OD units and can measure a 10,000-fold range of 14C or 35S isotope concentrations on autoradiograms. The complete device can be assembled with a hobbyist's knowledge of electronics, moderate programming abilities (no machine language required), and a cost of less than $3000, not including the IBM PC. PMID- 1862933 TI - Enzyme-amplified rate conductimetric immunoassay. AB - A new immunoassay technique based on measurement of conductance changes in solutions is described. The assay employs an immobilized monoclonal antibody to capture a protein analyte along with a second antibody to the same analyte, conjugated to an enzyme capable of producing ions which are measured conductimetrically. Urease was selected as the enzyme, because it produces, from urea, four ions for each catalytic event. The analyte studied was human chorionic gonadotropin in serum. Higher concentrations of analyte during incubation with immobilized antibody and antibody-urease conjugate led to increased binding of the latter. After removal of unbound conjugate, urea solution was added and the rate of conductance change measured in the bulk substrate solution. Experiments, performed in polystyrene microtiter wells using a specially designed electrode, demonstrated the ability to measure 30 picomolar concentrations of human chorionic gonadotropin with a 30-s rate measurement. Urease proved to be an excellent labeling enzyme, retaining its activity under the nonionic conditions necessary to maintain low background conductance. Good agreement was obtained between observed rates and those expected from conductimetric theory and known physical parameters. The potential utility of the conductimetric immunoassay lies in the fabrication of biosensor devices for simplification and cost reduction of immunochemical-based instrumentation. Further improvements to the technique are proposed to achieve lower detection limits. PMID- 1862934 TI - Vaccinia-T7 RNA polymerase expression system: evaluation for the expression cloning of plasma membrane transporters. AB - The vaccinia/T7 transient expression system, which results in rapid, high-level expression of proteins encoded by plasmids bearing T7 promoters, provides a powerful strategy for the expression cloning of membrane transporters. To test the feasibility of this approach, we introduced the rabbit Na+/glucose transporter by liposome-mediated transfection into vaccinia infected HeLa cells and determined the characteristics and sensitivity of induced [14C]alpha-methyl D glucopyranoside uptake. We observed a rapid (4-12 h) expression of saturable (Kt = 342 microM) [14C]alpha-methyl D-glucopyranoside uptake following transfection, with substrate and inhibitor sensitivities of the native carrier, including Na+ and temperature dependence and appropriate phloridzin sensitivity (KI = 9.1 microM). The time-dependent increase in alpha-methyl D-glucopyranoside uptake coincided with a decline in endogenous Na+/D-aspartate transport. Maximal levels of expression achieved were nearly 10-fold higher than that reported for transient expression of Na+/glucose transporters in the COS cell system. Rate and dilution estimates demonstrates a sensitivity of detection of single clones diluted several thousand fold by nonspecific plasmid DNA. A further 3-fold increase in transport sensitivity was achieved after transfection of plasmid constructs bearing additional 5'-T7 stem-loop and 3'-T7 termination signals. When cell lines with low endogenous transport were coupled with substrates of high specific activity, as with measurements of induced [3H]gamma-aminobutyric acid uptake, we were able to detect expression from transporter bearing plasmids diluted as much as 10,000-fold by non-specific plasmid DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1862935 TI - Isolation of intact mitochondria and hepatocytes using vibration. AB - A method of isolation of rat liver cells and mitochondria suggesting tissue disaggregation by vibration has been proposed. Mitochondria obtained using vibration have better parameters of oxidative phosphorylation as compared to homogenization. Hepatocytes isolated by vibration had viability about 90%, as determined by trypan blue exclusion, and rates of respiration and xenobiotic metabolism comparable to that observed by the enzymatic method. PMID- 1862937 TI - Use and detection of nonradioactive iodine-labeled antibodies for immunoassay. AB - Traditionally radioactively labeled iodine has been used as a reporter group for the detection of antibodies in immunoassay. We have recently developed a microassay system for the detection of very low concentrations of iodide which eliminates the need for the use of radiolabeled iodine (O'Kennedy, R. et al. 1989, Anal. Biochem. 179, 138-144). The successful application of this assay for the detection of mouse IgG is described. The performance of this system compared with enzyme immunoassay was evaluated. PMID- 1862936 TI - Spectral and photophysical studies of benzo[c]xanthene dyes: dual emission pH sensors. AB - A series of fluorescent, long-wavelength, benzo[c]-xanthene dyes has been characterized for pH measurement in both excitation and emission ratio applications. The two general classes of these indicators are seminaphthofluoresceins (SNAFLs) and seminaphthorhodafluors (SNARFs) which are substituted at the 10-position with oxygen or nitrogen, respectively. These probes show separate emissions from the protonated and deprotonated forms of the fluorophores. The dyes may be excited at 488 or 514 nm with argon ion lasers. Most of the indicators have pKa values between 7.6 and 7.9. Detailed photophysical studies were conducted on the carboxy-SNAFL-1 system and excited state prototropic reactions were compared to structurally related derivatives, such as the umbelliferones. Membrane permeant esters, such as diacetates and acetoxymethyl esters have also been prepared. The indicators are spectrally well resolved from calcium indicators such as fura-2 and indo-1 and should be suitable for simultaneous determination of pH and Ca2+ transients. PMID- 1862938 TI - One-step purification of bacterial lipid macroamphiphiles by hydrophobic interaction chromatography. AB - Bacterial lipid macroamphiphiles extracted with phenol/water can be purified in one step by hydrophobic interaction chromatography. Lipids and the major part of protein are separated from macroamphiphiles during phenol/water extraction. Coextracted nucleic acids, polysaccharides, and residual protein are effectively removed by column chromatography on octyl-Sepharose whereby macroamphiphiles are primarily adsorbed and later eluted with a buffered propanol gradient. The procedure is applicable to macroamphiphiles with various lipid structures as was demonstrated using the diacylglycerol-containing lipoglycan of Micrococcus luteus, the lipid A-containing lipopolysaccharide of Salmonella typhimurium, and the diglyceryl tetraether lipoglycans of Thermoplasma acidophilum and Thermoplasma volcanicum. On elution from octyl-Sepharose, separation into molecular species of different compositions was observed with the lipopolysaccharide of S. typhimurium and the lipoglycan of T. volcanicum. It was also shown that, after phenol/water extraction, membrane lipids are completely recoverable from the phenol layer, which makes it possible to isolate lipids along with macroamphiphiles from the same sample of bacteria. PMID- 1862939 TI - Monoclonal antibody to calmodulin: development, characterization, and comparison with polyclonal anti-calmodulin antibodies. AB - Specific anti-calmodulin rabbit polyclonal and murine monoclonal antibodies have been produced with a thyroglobulin-linked peptide corresponding to amino acids 128-148 of bovine brain calmodulin. The monoclonal antibody is IgG-1 with kappa light chains. Both sets of antibodies recognize native vertebrate calmodulin, with the polyclonal antibody exhibiting an approximately fourfold higher sensitivity than the monoclonal antibody in a radioimmunoassay. The affinity of both polyclonal and monoclonal antibodies is approximately 2.5-fold higher for Ca(2+)-free calmodulin than for Ca(2+)-calmodulin. Other selected members of the calmodulin family (S100, troponin, and parvalbumin) do not exhibit significant cross-reactivity with the monoclonal antibody. Troponin and S100 beta displace some 125I-calmodulin from the polyclonal antibody, but require at least 900-fold excess concentration. The monoclonal antibody recognizes intact vertebrate calmodulin in solution and also on solid-phase. In addition, plant calmodulin and some forms of post-translationally modified calmodulin (phosphorylated or glycated) bind the monoclonal antibody. The affinity of the monoclonal antibody is approximately 5 x 10(8) liters/mol determined by displacement of 125I calmodulin. On dot blotting the sensitivity for vertebrate calmodulin is 50 pg. The epitope for the monoclonal antibody is in the carboxyl terminal region (residues 107-148) of calmodulin. This highly specific anti-calmodulin monoclonal antibody should be a useful reagent in elucidating the mechanism by which calmodulin regulates intracellular metabolism. PMID- 1862940 TI - Detection of mercuric ions in water by ELISA with a mercury-specific antibody. AB - An immunoassay that detects mercuric ions in water at concentrations of 0.5 ppb and above is described. The assay utilizes a monoclonal antibody that binds specifically to mercuric ions immobilized in wells of microtiter plates. Within the range of 0.5-10 ppb mercury, the absorbance in the enzyme-linked immunosorbent assay (ELISA) is linear to the log of the mercuric ion concentration. The quantitation of mercury by ELISA correlates closely with results from cold-vapor atomic absorption. Other divalent metal cations do not interfere with the assay, although there is interference in the presence of 1 mM chloride ions. The optimum pH for mercury detection is 7.0, although 2 ppb mercury can be detected over a wide pH range. The assay is as sensitive as cold vapor atomic absorption for mercury detection and can be performed with only 100 microliters of sample. PMID- 1862941 TI - Detection of endopeptidase activity and analysis of cleavage specificity using a radiometric solid-phase enzymatic assay. AB - A radiometric procedure to detect the presence of proteolytic enzymes and analyze their substrate specificity is described. The enzymatic activity is first measured by the release into solution of a radiolabeled reporter group from an immobilized peptidyl substrate. Two peptidyl substrates encompassing multiple cleavage sites, a derivative of Leu-enkephalin and a peptide related to the bait region of human alpha 2-macroglobulin, are prepared and linked via a spacer molecule to an insoluble support. The labeled peptides released are then separated by high-performance liquid chromatography. The position of the released peptides upon chromatography allows direct identification of the sites of cleavage. The assay, using a radioactive iodinated tyrosine residue as reporter group, is extremely sensitive (less than 0.02 pg/ml of trypsin), reproducible, and easy to perform while yielding unambiguous identification of the sites of cleavage. This assay can be used to detect the presence of enzymatic activities and/or of enzyme inhibitors. Furthermore, it can be easily adapted to detect from a variety of sources all four classes of enzymes known by using appropriate peptidyl substrate sequences, buffer, pH, and incubation conditions. PMID- 1862942 TI - Subcellular fractionation of murine erythroleukemic cells: distribution of protein kinases. AB - A method for subcellular fractionation of murine erythroleukemic cells is described; a highly purified cytosol fraction and significantly enriched membrane, mitochondrial, and nuclear fractions were obtained. During development of the procedure, we demonstrated how the composition of the extraction buffers and the techniques used can affect activity and distribution of protein kinases. Protein kinases in the various fractions were separated by nondenaturing electrophoresis and detected by phosphorylation and autoradiography. Differences in the relative proportions of the kinases, which may be significant in relation to differentiation, were seen in all the fractions on hexamethylenebisacetamide treatment of the cells. PMID- 1862943 TI - A microassay for the pore-forming activity of complement, perforin, and other cytolytic proteins based on confocal laser scanning microscopy. AB - A fluorescence microscopic assay for the activity of complement, perforin, and other cytolytic proteins which form transmembrane pores in cellular membranes is described. The assay was worked out and tested with red blood cell membranes (ghosts) and was then applied to intact hemoglobin-free cells. Resealed human erythrocyte ghosts were incubated with complement or perforin. A small polar fluorescent probe (fluorescein-labeled 1-kDa dextran, FD1) which permeates through complement and perforin pores but not through normal cell membranes was added to the samples. The capability of the confocal laser scanning microscope (CLSM) to generate thin optical sections was exploited to visualize and quantitate fluorescence inside single ghosts and thus determine the fraction of ghosts which had become permeable for FD1. The activity of complement or perforin was quantitated by plotting the fraction of permeable cells versus the concentration of the pore-forming protein. The results were in good agreement with those of a conventional hemolytic assay. The CLSM-based assay was then applied to intact hemoglobin-free cells for which only few alternative assays are available. Compared to conventional hemolytic assays for the activity of pore forming proteins the assay described here can be applied to a large variety of natural and artificial membrane systems. The assay can be performed under nonlysing conditions. Furthermore, the assay is simple, relatively fast, and requires only extremely small amounts of cells and pore-forming proteins. PMID- 1862944 TI - Reverse immunoaffinity chromatography: application to the purification of the 60- to 90-kDa gastric parietal cell autoantigen associated with autoimmune gastritis. AB - Previous attempts to purify autoantigens by affinity chromatography using the total IgG from autoantibody-positive sera have not been very successful. We describe here a novel method using parietal cell autoantibodies, isolated on a crude autoantigen immunoabsorbent column, for the purification of the 60- to 90 kDa gastric parietal cell antigen targeted in autoimmune gastritis. The 60- to 90 kDa parietal cell antigen was first enriched 2.5-fold from a 0.5% Triton X-100 extract of total pig gastric mucosal membranes by DEAE-Sepharose 4B chromatography. The fraction containing the 60- to 90-kDa antigen was directly coupled to CNBr-activated Sepharose 4B to produce an immunoadsorbent column for the "reverse" purification of the specific parietal cell autoantibodies from pooled gastric parietal cell autoantibody-positive human sera. A 0.5% Triton X 100 extract of pig gastric mucosal membranes was initially precleared by sequential passage through Protein A-Sepharose 4B and normal human Ig-Sepharose 4B columns. The 60- to 90-kDa gastric parietal cell antigen (approximately 10 micrograms) was then purified from this precleared Triton X-100 membrane extract by affinity chromatography on a 1-ml column of purified autoantibody-Sepharose 4B, followed by preparative sodium dodecyl sulfate-polyacrylamide gel electrophonesis. This method, incorporating a "reverse" immunoaffinity chromatography step, has general applicability for the purification of tissue autoantigens using highly specific autoantibodies present in the sera of humans and experimental animals with a variety of other autoimmune diseases. PMID- 1862945 TI - Separation of large DNA by a variable-angle contour-clamped homogeneous electric field apparatus. AB - A device for separating large DNA molecules by pulsed field electrophoresis is described. Based on the principles of contour-clamped homogeneous electric fields (CHEF), it uses feedback to clamp voltages in a square electrode array, which is compact and inexpensive to construct, adaptable to computer control, and reorients the electric field by arbitrary angles. To illustrate its capabilities, pulsed fields with reorientation angles ranging from 90 to 140 degrees were used to separate DNAs of 4.7 and 5.7 megabases by up to four band-widths in 20 h. The combination of accessible technology and complete control of the electric field should facilitate the search for ways to resolve even larger DNA. PMID- 1862946 TI - Distribution and targets of the cartwheel cell axon in the dorsal cochlear nucleus of the guinea pig. AB - This investigation attempted to determine the mode of distribution and synaptic targets of the cartwheel cell axon in the guinea pig dorsal cochlear nucleus (DCoN). Antiserum against PEP-19, a putative calcium-binding neuropeptide, was employed at the light and electron microscopic levels. We show that in the hind brain of the guinea pig, cerebellar Purkinje cells and DCoN cartwheel cells are the most densely immunoreactive neurons. The PEP-19 immunoreaction product is localized to all neuronal compartments of these cells. Primary targets of cartwheel cell axons are the DCoN pyramidal cells, the large efferent neurons of layer 2. These neurons receive numerous immunoreactive synaptic boutons on their cell bodies and apical and basal dendritic arbors. A PEP-19-immunoreactive axonal plexus, largely formed by cartwheel cell axons, highlights layer 3, co extensively with the basal arbors of pyramidal cells. This plexus is oriented predominantly in the transstrial plane of the DCoN, in parallel with the sheet like basal dendritic arbor of pyramidal neurons and with the isofrequency bands of primary cochlear nerve fibers. PEP-19-positive boutons contain pleomorphic synaptic vesicles and form symmetric synaptic junctions, indicative of inhibitory innervation. In addition, immunoreactive boutons, similar to those synapsing on pyramidal neurons, were observed on the cell bodies and main dendritic trunks of cartwheel neurons, indicating a system of recurrent collaterals. Furthermore, a small number of PEP-19-positive axons of unknown origin reach the caudal rim of the posteroventral cochlear nucleus. Within the territory of distribution of the cartwheel cell axon are the dendrites of at least two other types of DCoN neuron, the vertical cells of Lorente de No and the giant cells. These neurons may represent additional targets of the cartwheel cell axon, but this remains to be ascertained with specific methods. Our data demonstrate that the cartwheel neurons modulate the activity of pyramidal neurons and, therefore, play a key role in shaping the output of the DCoN superficial layers. PMID- 1862947 TI - Estrogenic modulation of met-enkephalin-induced prolactin secretion in rats. AB - In order to elucidate the possible role of estrogens in the sex-dependent modulation of met-enkephalin-induced prolactin secretion, and the cellular response at adenohypophyseal level, analyses of serum prolactin levels together with a morphometric study of prolactin-immunoreactive cells were carried out following intraventricular administration of the opioid to estrogen-primed male rats. Administration of the opioid led to an increase in the serum levels of the hormone and, morphometrically, a significant increase in the cellular, cytoplasmic and nuclear areas was observed. When naloxone was administered previously, the above, mentioned changes did not appear, and the values found were similar to those observed in the animals treated only with estrogens. The results suggest that the metenkephalin-induced prolactin secretion is modulated by the gonadal steroid environment. PMID- 1862948 TI - Concomitant changes in endothelial cell junctions and extracellular matrix components in the chick embryo aorta. AB - According to previous studies, a process of endothelial activation seems to be occurring in the chick embryo between days 7 and 18. Also, endothelial cells respond to collagen as a substratum between 12 and 18 days, and this response diminishes until it almost disappears after birth. In the present study, aortas from chick embryos (days 7 to 21), and from chicks (14 days posthatching) were used. The results obtained by the freeze-fracturing technique, showed that between days 12 and 14 the intramembranous particles were aggregated into linear or clustered arrays in the fracture P-face of endothelial cells. This could signify that some kind of gap junction-like coupling may occur between adjacent endothelial cells. Our results also indicate that in advanced stages (21-day-old chick embryos and 14-day-old chicks) the growth of small aggregates into larger aggregates or plaques could occur. In addition to gap junctions, the presence of macular and linear tight junctions, reported as focal tight junctions (day 14 of development) macular and linear tight junctions with free-ending strands oriented parallel to one another (21 days) and smooth contoured ridges (14 days post hatching) were observed. This sequence of changes may represent a development from linear to macular, to a more occluding arrangement, and may also reflect an endothelial cell polarization. Histochemical study of proteoglycans was done by using cuprolinic blue according to the critical electrolyte concentration method. Cuprolinic blue-positive granular, elongated and microfibrillar materials were found in the subendothelial region, forming a meshwork that occupies the extracellular space. Qualitative and quantitative changes were observed both in proteoglycans and in other extracellular matrix components throughout development, suggesting an increase in extracellular matrix complexity. These results lead us to suggest that the assembly of a more complex extracellular matrix, concomitantly with the formation of intercellular junctions during development, might influence the polarization of endothelium in the aorta of the chick embryo. PMID- 1862949 TI - Elastic-like tissue, a new component of the renal glomerular capillary wall in a cartilaginous fish. AB - Elastic-like tissue composed of tubular microfibrils continuous with, and disappearing into, amorphous material is present in the connective tissue space of the glomerular capillary wall of the river ray (freshwater elasmobranch) kidney. The amorphous material is stained by tannic acid but not by uranyl acetate. Structures with similar morphology and staining characteristics are also found in the subendothelial connective tissue layer of renal arteries in this species. Comparative ultrastructural observations of kidneys from marine rays show elastic-like tissue in the arterial wall but not in the glomerular vessels. PMID- 1862950 TI - ChAT-like immunoreactivity of olivocochlear fibres on rat outer hair cells during the postnatal development. AB - Several studies present a great deal of information about putative efferent neurotransmitters and their distribution in the adult and developing cochlea. Anatomical mapping of outer hair cell efferent fibres during ontogeny is still not available. Using quantitative electron microscopy in combination with immunocytochemistry, the distribution of ChAT-like immunoreactivity in the developing rat was investigated. Adult-like immunoreactivity in the whole cochlea is first observed in 30-day-old rats. We localized the adult-like immunoreactivity in all efferent fibres and synapses of the outer hair cells along the entire cochlear duct. An adult-like reaction in the whole cochlea could be observed on the 25th day after birth in two out of three cases. On the 20th postnatal day, no adult-like ChAT immunoreactivity was found, with the exception of one case where labelling was seen in the basal region only. The adult-like ChAT immunoreactivity on the 30th day, 2-3 weeks after the onset of hearing, is the latest maturation of all features of the organ of Corti so far investigated. Synaptogenesis of the outer hair cell efferents reaches an adult-like appearance already on the 16th day after birth. PMID- 1862951 TI - Development of cranial nerves in the chick embryo with special reference to the alterations of cardiac branches after ablation of the cardiac neural crest. AB - Development of cranial nerve branches in the cardiac region was observed in whole mount specimens which were stained with a monoclonal antibody, E/C8, after the ablation of the cardiac neural crest. In early embryos, nerve trunks of IX and X were lacking or only poorly developed, while the early development of pharyngeal branch primordia was normal. In day 5 embryos, the nerve trunks of IX-X were present in all the embryos, however; extensive communication was observed between X and XII. On day 6 and later, the spiral pattern of superior cardiac branches was disturbed, as were the blood vessels. Furthermore, the distal branches of XII passed within the superficial layer of cardiac outflow mesenchyme. Vagal branches passed within the deeper layer. There was no apparent change in the development of the sinal branch. Using quail--chick chimeras, it was found that the cardiac neural crest cells formed the Schwann cells of XII, and that they were also associated with the hypobranchial muscle primordium, suggesting that the absence of the cardiac neural crest not only disturbs the development of the cardiac outflow septation, but also affects the normal morphogenesis of the hypobranchial musculature and its innervation. Embryologically, the tongue is located close to the cardiac outflow tract, which is the migration pathway of the cardiac neural crest-derived cells. PMID- 1862953 TI - [Hemodynamics during epidural anesthesia in combination with transcranial electroanesthesia in pulmonary surgery]. AB - Pulmonary surgery performed under epidural anesthesia (EA) combined with transcranial electrical anesthesia (TEA) was characterized by minimum adverse hemodynamic reactions, typical of EA alone, and reduced overall dose of the local anesthetic with minimum volume of the infusion therapy and adequate anesthetic protection. The absence of marked hemodynamic reactions in this type of combined anesthesia made it possible to use it during pulmonary surgery in the most severely ill patients whose cardiovascular system is already compromised by the primary pulmonary disease. PMID- 1862952 TI - Immunohistochemical localization of endothelin-like immunoreactivity in human tooth germ and mature dental pulp. AB - The distribution in oral tissues of endothelin, a multifunctional peptide originally identified within endothelial cells, and subsequently in some epithelial cells, neurons and neuroendocrine cells, has not been investigated yet. We have studied the localization of endothelin-like immunoreactivity in human tooth germ and mature dental pulp by immunohistochemical techniques. Such immunoreactivity was detected only within endothelial cells in both mature dental pulp and developing tooth. Arteries and veins of various sizes as well as small thin vessels displayed endothelin-like immunoreactivity. In the tooth germ, the cells of the enamel organ or the precursors of the odontoblasts were found unreactive. In the mature pulp, no cells of the stroma or nerves displayed endothelin-like immunoreactivity. These findings suggest that vascular endothelium may be the only source of endothelin in human dental tissues. It is tentatively proposed that endothelin released in mature tooth pulp may participate in the regulation of the pulpal blood flow. Although the possible role of endothelin in developing tissues is far from being clear, the mitogenic effects and the proto-oncogenes expression induced by endothelin in some cells raise the possibility that this peptide might also play a role during tooth development. PMID- 1862954 TI - [Evaluation of the cardiac pump function and the adequacy of infusion therapy in heart surgery patients in the early postoperative period]. AB - 149 patients after open-heart surgery (correction of heart valve defects and aortocoronary bypass surgery) have been examined. Volume expansion was performed by rapid intravenous infusion of 200-800 ml of fluid. Hemodynamic parameters were studied by direct methods. Patients with initially high heart chamber filling pressure were subject to forced diuresis (bolus intravenous injection of 1-2 mg lasix), the changes in hemodynamic parameters were registered with gradual fluid excretion. Left ventricular function curves were plotted in the coordinates: stroke heart work or stroke index--left ventricular end diastolic pressure. A down slope of the Starling curve was registered in 34% of patients, which was indicative of heart failure, volume overload of the myocardium or was prognostically unfavourable as to the onset of heart failure. The values of left ventricular diastolic pressure, when a down slope was registered, varied from 3-5 to greater than or equal to 20 mm Hg, depending on myocardial contractility and diastolic function. Peripheral vasodilation was the earliest sign of the myocardial volume overload. Volume load test proved to be ineffective in 27% of patients and insufficiently effective in 13.7% of patients. PMID- 1862955 TI - [Carbohydrate metabolism in patients with diabetes mellitus under epidural anesthesia]. AB - A certain effect of surgical intervention on glucose, insulin and cortisol content has been shown in patients without concomitant endocrine pathology operated on for urological and gynecological diseases under epidural anesthesia. At the same time rational manifestations of the adaptation mechanisms of carbohydrate metabolism were retained. The use of epidural anesthesia has demonstrated the lack of carbohydrate hypermetabolism excess in the intra- and postoperative periods in patients with concomitant diabetes mellitus. This makes the epidural anesthesia a method of choice during surgery in patients with concomitant diabetes mellitus. PMID- 1862956 TI - [Hemodynamic disorders and their correction in the newborn following abdominal surgery]. AB - Central hemodynamics was studied, using echocardiography and dopplercardiometry in 48 newborn operated on the abdominal organs. General regularities of hemodynamic changes in the first postoperative hours irrespective of the initial type of circulation have been established. Two types of cardiovascular system response to the operation stress are described; an increase and a drop in the cardiac output, which is extremely important for the diagnosis of impaired compensatory-adaptive mechanisms in the newborn. Special attention was paid to the assessment of the adequacy of the infusion therapy. Volume-load test facilitates the diagnosis of latent heart failure. Timely prescription of cardiotonic drugs and differential approach to infusion therapy prevent the onset of circulatory disturbances. PMID- 1862957 TI - [Acceleration of the restoration of conditioned reflexes following anesthesia using aminostigmine]. AB - The effect of anesthesia with ketamine (80 mg/kg, intraperitoneally) combined with phenazepam (0.5 mg/kg, subcutaneously) on the reproduction of an elaborated active avoidance reflex in automated reflexometer has been studied on random bred white rats. In has been shown that during 3 hours after the animal is taken out of the lateral position the degree of its learning is significantly lowered and does not return to baseline even a day later. Intramuscular administration of a new cholinesterase inhibitor aminostigmine right after the end of anesthesia restores the disrupted reflex in 3 hours. The optimal antistigmine dose is 0.015 mg/kg, which corresponds to a therapeutic human dose. PMID- 1862958 TI - [Disorders of thermoregulation in the resuscitation period following clinical death]. AB - Pharmacological analysis of the functioning of mechanisms responsible for central regulation of temperature homeostasis in the postresuscitation period has been performed in experiments on dogs survived after clinical death of various duration. Thermoregulation disturbances after clinical death are caused by impaired mediator relationships in the CNS and sensor function of thermosensitive hypothalamus neurons. The mechanisms of thermoregulation disturbances are of multifocal nature and are to a great extent dependent on the degree of brain damage in critically ill patients. PMID- 1862959 TI - [The outlook for the use of pulse oximetry in anesthesiology and resuscitation]. PMID- 1862960 TI - [Intensive therapy in syndromes of disorders of cerebral blood circulation in the bed of the anterior cerebral arteries following the removal of middle basal tumors]. AB - 255 patients have been examined in the early postoperative period after the removal of tumors located in diencephalic and sella turcica regions. The early postoperative period was complicated by circulation disturbances in the vascular bed of the anterior cerebral or anterior communicative arteries. The clinical pattern, CT scans and morphological data were analysed. Three principal clinical syndromes of the postoperative period were lined out: 1) extrapyramidal diencephalic syndrome; 2) extrapyramidal-capsular syndrome; 3) frontal corpocallosal syndrome. The reason for these syndromes was the occlusion of the anterior cerebral and anterior communicative arteries or their branches. The diencephalic syndrome had poor prognosis. The postoperative therapy included hormones. It was necessary to prevent the onset of adrenal insufficiency and diabetes insipidus. The differential diagnosis of thrombosis and vasospasm was of great importance. In case of vasospasm, such medicines as sermion, redergine and nimodipine had a strong therapeutic effect. In vascular thrombosis these medicines were ineffective. Systemic approach to circulation disturbances seems of utmost importance for the analysis of postoperative complications. PMID- 1862962 TI - [AIDS, hepatitis and anesthesiology]. PMID- 1862961 TI - [Determination of the level of heparinization necessary to provide cascade filtration exchange plasmapheresis in patients with generalized suppurative peritonitis]. AB - Activated clotting time was determined during cascade filtration exchange plasmapheresis (CFEP) in 24 patients with generalized suppurative peritonitis. A modified method of activated clotting time determination, using a home-made infusorial earth substitute of the type of "Kieselguhr" was used. A gradual decrease in activated clotting time during CFEP has been observed, which required additional heparin administration. By the end of the procedure, when the removed plasma volume reached 1500 ml, activated clotting time values returned practically to baseline. PMID- 1862963 TI - [The new Soviet narcotic analgesic phenaridine as a component of general anesthesia during cancer surgery]. AB - The results of studies on 65 cancer patients operated on under modified neuroleptanalgesia using fenaridine give evidence of a more potent and prolonged analgetic effect of a new Soviet narcotic analgesic fenaridine as compared to fentanyl. Fenaridine ensures stable neuroautonomous protection of the body during cancer surgery and is indicated in prolonged traumatic surgical interventions with cardiopulmonary bypass. Along with the above advantages fenaridine possesses all the complex of side effects typical of opiates associated with the depression of respiratory centres, psychoemotional sphere, activation of parasympathetic centres which may complicate the period following the patient's withdrawal from anesthesia and necessitate prolonged controlled lung ventilation in the early postoperative period. Thus, during 3-5-hour-long surgery it is advisable to administer the basic amount of the overall drug dose during the first 1-1.5 h of anesthesia and surgery, which promotes the awakening of most patients 10-15 min after surgery. Another drawback of fenaridine is the onset of marked rigor and signs of microcirculation disturbances upon discontinuation of the drug effect. PMID- 1862964 TI - [Anesthesiologic protection of the mother and fetus during abdominal delivery]. AB - Central hemodynamics at different stages of anesthesia, changes in hexenal concentration in the mother's body, adequacy of anesthesia and hexenal effect on the condition of the fetus and newborn have been studied in 40 pregnant women without any accompanying extragenital pathology subject to planned cesarean section performed under combined general anesthesia. Normodynamic type of circulation has been established. The analysis of blood catecholamine changes confirmed the adequacy of the anesthesia. The studies of hexenal concentration have demonstrated the absence of negative effect on the newborn delivered by cesarean section. PMID- 1862965 TI - [Perioperative dynamics of the parameters of acid-base equilibrium in patients with lung cancer in relation to the type of anesthesia]. AB - Acid-base parameters of the venous blood have been studied in 60 patients with lung cancer randomized into two groups prior to and following lung resection and on days 2, 4 and 9 postoperatively. In group I multicomponent endotracheal anesthesia using controlled lung ventilation and postoperative intramuscular analgesia with non-narcotic and narcotic analgesics were employed. In group II anesthesia and controlled lung ventilation were supplemented by epidural anesthesia with 2.5% trimecaine solution combined with adrenaline and small morphine doses at the upper thoracic segment level, postoperative analgesia for 18 hours was performed likewise. Perioperative acid-base balance changes were found to be more favourable in patients of group II, which was manifested in weaker acidosis by the end of the operation and in the absence of remote pathological changes in the acid-base balance. In patients of group I gradual repeated increase in metabolic acidosis was observed, which by day 9 postoperatively assumed a complicated clinical course. PMID- 1862966 TI - [The use of sodium nitroprusside in the treatment of heart failure in critically ill children]. AB - Sodium nitroprusside was used in 18 children aged 1 to 13 years with clinical and hemodynamic signs of low cardiac output syndrome secondary to septic pancarditis, lung edema, thromboembolism of pulmonary artery branches. Central and peripheral hemodynamics has been studied by impedance plethysmography prior to and during the first day of sodium nitroprusside infusion. A considerable improvement of hemodynamic parameters and the patients' conditions has been established. Effective dosages and indications for the drug use in children have been elaborated. PMID- 1862967 TI - [The use of pyrazidol during treatment using hyperbaric oxygenation therapy]. AB - The effect of pyrazidol on the efficiency of hyperbaric oxygenation (HBO) was investigated. Pyrazidol administration before HBO procedure reduced the intensity of lipid peroxidation in the blood plasma and decreased destabilization of erythrocyte membranes. Exoerythrocyte hemoglobin concentration, total peroxidase activity and glucose-6-phosphate dehydrogenase activity were used as the indexes of membrane stability. The patients pretreated with pyrazidol bore HBO much better than other patients. PMID- 1862968 TI - [Controlled combination anesthesia]. AB - The improvement of combined anesthesia is associated with the improvement of its control. The latter is possible only with continuous administration of anesthetics. 130 procedures of combined anesthesia were performed in patients subject to abdominal and other types of operations. With this in view fentanyl and calipsol were continuously injected, using modified dosators, to patients pretreated with N2O and total curarization. It has been found that with continuous administration adequate analgesia with stable blood pressure can be achieved provided that 1/3-2/3 of the total fentanyl dose is used as a loading dose at the beginning of anesthesia. The maintenance dose does not change considerably blood anesthetic concentration. If required, changes in the concentrations were achieved by additional fentanyl administration, using a dosator for 25-50 mukg. The technique described has advantages over bolus drug injection and continuous drug infusion. The technique may be considered a controlled one. PMID- 1862969 TI - [Continuous intravenous administration of fentanyl during multicomponent anesthesia in children]. AB - 136 anesthetic procedures during planned and emergency surgery in children have been analysed. It has been demonstrated that non-stop intravenous fentanyl injection with an automated syringe of "Lineomat" type ensures an adequate analgesia over a 2-10 h period. The adequacy of anesthesia was confirmed by the data of central and peripheral hemodynamics monitoring, acid-base balance, temperature gradient and clinical course. Non-stop injection of the analgesic made it possible to reduce the drug expenditure by 30% on average as compared to the theoretically calculated dose, as well as to free paramedical personnel and decrease their exposure to blood. PMID- 1862970 TI - [A case of successful treatment of post-resuscitation disease in a patient with strangulation asphyxia]. PMID- 1862971 TI - [The surfactant system of the lungs in the postoperative period]. AB - Pulmonary surfactant has been investigated in the postoperative period in 68 patients. Acute postoperative respiratory failure develops in patients with marked disturbances of respiratory mechanics. In patients with shock changes in surface-active substances develop on the 2nd-5th day after its onset. PMID- 1862972 TI - [Activated forms of O2 and their role in pathological conditions]. PMID- 1862973 TI - [Heparin therapy of disseminated intravascular coagulation in pyo-inflammatory diseases in children]. PMID- 1862974 TI - [Characteristics of the changes in the concentration of 2,3-diphosphoglycerate in heart surgery patients]. AB - Changes in 2,3-DPG level have been studied in cardiosurgical patients. It has been shown that 2,3-DPG concentration increase, as a moderately fast mechanism in a common model of tissue pO2 regulation, is observed in almost half of patients with acquired heart valve defects. An increase in 2,3-DPG level and P50 value leading to a decrease in hemoglobin affinity to oxygen has been found in one third of patients. It has been established that 2,3-DPG level and P50 value are, as a rule, normal in patients with mitral stenosis, acyanotic congenital heart valve defects and ischemic heart disease. In a number of patients with mitral stenosis an increased Hb concentration, as a slow mechanism of hypoxia compensation in the model of tissue pO2 regulation, is a prevailing mechanism of adaptation to hypoxia. PMID- 1862975 TI - [The use of microcomputers for calculating the indices of the hemodynamics, pump and contractile function of the left heart]. AB - A programme is presented for the calculation of parameters reflecting pump and contractile functions of the left ventricular myocardium on Soviet-made microcomputer B3-34. The programme makes it possible to intensify studies 2.5-3 fold, assess hemodynamics many times at different stages of the investigation, obtain results and promptly give practical recommendations, which is of utmost importance in intensive care and resuscitation. PMID- 1862976 TI - [The dependence of sensory perceptions on the predominance of parasympathicotonia or sympathicotonia during preoperative psychoemotional stress]. AB - Low tactile and pain thresholds and high Kerdo index were observed in patients with sympathicotonia predominance during preoperative emotional stress. Low Kerdo index and high tactile and pain thresholds were observed in patients with parasympathicotonia predominance during preoperative psychoemotional stress. PMID- 1862977 TI - [The content of calcium and magnesium in official Soviet solutions used in extracorporeal circulation, anesthesia and resuscitation]. AB - Total calcium (CaT) and total magnesium (MgT) levels have been determined in 21 solutions used in cardiopulmonary bypass surgery and manufactured in the USSR. It has been found that a great number of solutions differ in CaT content from human plasma. Some solutions contain Ca, which is not required by the prescription. Even in one and the same lot solutions vary greatly in Ca content (gelatinol). A large number of the solutions tested does not correspond to blood in MgT content, either. Like Ca, this parameter is quite unstable. Such differences in CaT and MgT levels practically in all standard Soviet-made solutions make it impossible to determine accurately precise amount of the solution required. The optimal way of hypercalcemia and hypermagnesiuemia prevention is the elaboration of the solutions identical to blood in their Ca and Mg content, or the use of colloids, practically free of electrolytes (hexaethyl starch). PMID- 1862978 TI - [The effect of premedication using promedol and galanthamine on the course of epidural anesthesia with trimecaine]. AB - The course of epidural anesthesia with a 2% trimecaine solution has been studied in 93 patients (mean age 56.5 years) upon premedication with promedol (20 mg) and galanthamine (10 mg). It has been established that promedol promotes mainly to a reduction in the time of anesthesia onset (by 26.5%) and to the enhancement of the antihypertensive reaction (by 15.7%). Premedication with galanthamine is accompanied by a 13% decrease in the initial anesthetic dose, a 34.5% shortening of the time of anesthesia onset and the attenuation of negative hemodynamic shifts. Upon premedication with both drugs, the total trimecaine expenditure decreases by 25% and the time of anesthesia onset shortens more than by half. PMID- 1862979 TI - [The choice of anesthesia for endoscopic interventions in the upper digestive tract]. AB - The efficacy of local anesthesia during upper abdominal endoscopy was compared to that of local anesthesia in combination with moradol. Local anesthesia of the throat combined with intramuscular moradol (0.04 mg/kg) helps retain psychoemotional indifference and stable hemodynamic and autonomous system parameters in such traumatic moments of the endoscopy as irritation and dilatation, which cannot be said of patients who were subject to such interventions under local anesthesia alone. PMID- 1862980 TI - [Changes in hemodynamics during intermittent high-frequency ventilation of the lungs in patients with acute respiratory insufficiency]. AB - Hemodynamic changes have been studied in 19 patients (30 observations) with acute respiratory failure of various genesis during transition from conventional controlled lung ventilation, performed using PO-6 and Phase-3C devices, to intermittent high-frequency jet ventilation ("Spiron 601"). Impedance plethysmography and rheopulmonography have been used. It has been established that intermittent high-frequency jet ventilation during 1 hour can have both positive and negative effect on systemic and pulmonary hemodynamics in patients with lung damage. It has been demonstrated that the type of reaction depends on the initial values of stroke volume and cardiac output. PMID- 1862981 TI - [Complications of anesthesia and means of lowering their frequency]. AB - Retrospective analysis of 9262 formalized case histories has been made to compile a protocol of anesthesia. Each blank contains 223 items describing the patient and is intended for retrospective computer analysis of the information. Phases of the complications onset have been established and a working classification of complications has been suggested. Organization measures, which reduced the frequency of complications by 2.4% have been elaborated. The factors that increase the frequency of anesthesia-induced complications are reviewed. PMID- 1862982 TI - [Iron-containing proteins in the plasma and serum of the blood in patients during hyperbaric oxygenation therapy]. AB - Extra-erythrocyte hemoglobin (EEH) level and total peroxidase activity (TPA) have been analysed in the blood serum and plasma of 44 patients following hyperbaric oxygenation (HBO). The levels of the parameters tested decreased after 3 HBO procedures and remained low to the end of the treatment period in the first group of patients. In the second group of patients, on the contrary, EEH and TPA levels increased after 3 HBO procedures and remained high to the end of the treatment period. In both groups of patients EEH changes correlated with TPA alterations. Possible EEH and TPA determination for the estimation and enhancement of HBO treatment efficacy is discussed. PMID- 1862983 TI - [The use of intravenous low-intensity laser irradiation of the blood in the total complex of anesthesiological protection of patients against surgical stress]. AB - 60 patients, aged 28 to 80 years, hospitalized for surgical treatment of various esophageal, gastric and intestinal diseases have been examined. In 30 patients (group 1) during surgery conventional neuroleptanalgesia was accompanied by intravenous low-intensity laser blood irradiation (ILILBI). The remaining 30 patients formed the control group. Unlike control patients, in patients of group 1 adequate perfusion and tissue oxygenation were maintained throughout the whole period of surgical intervention, general stress reaction to surgical trauma was less pronounced. The data obtained demonstrate the advisability of ILILBI introduction into a complex of anesthesiological protection. PMID- 1862984 TI - [Mechanism of the development of hypocoagulation disorders in the course of disseminated intravascular coagulation syndrome in newborn infants with pyo septic diseases]. AB - The development of hypocoagulation disturbances in sepsis of the newborn is mediated by the consumption of coagulation and vascular-platelet hemostasis factors. The formation of an insufficient clot in a number of patients may result in an increase of spontaneous fibrinolysis index, which does not correspond to the degree of decreased plasmin system activity due to its depletion. PMID- 1862986 TI - [Evaluation of the effect of extracorporeal ultraviolet irradiation of the autoblood of patients in terminal states based on indices of cellular immunity]. AB - The article presents the results of the effect of extracorporeal autoblood ultraviolet irradiation (UVI) on the parameters of cellular immunity in pyo septic complications of terminal conditions. To assess the activity of neutrophils the technique determining spontaneous and stimulated chemiluminescence with the calculation of activation index was used. The necessity of the control over immunologic parameters during selection of methods and time of UVI procedure is stressed. It has been established that UVI in patients with most severe conditions does not cause a sufficient increase in metabolic neutrophil reserve, which may account for the technique inadequacy in some cases. PMID- 1862985 TI - [Treatment of septic conditions in children using perfusion through a pig donor spleen]. AB - A technique of perfusion through pig donor spleen has been described with regard to peculiarities of the young age. Good therapeutic effect was observed during 12 splenoperfusions performed to 8 patients with septic conditions aged 12 days to 14 years. The technique suggested is simple and can be used under adequate anesthesiologic supply in children's hospitals. PMID- 1862987 TI - [Factors affecting the permeability of cellular and vascular membranes and changes in the enzyme spectrum of the blood in patients having undergone critical states and resuscitation]. AB - 126 patients recovered after critical conditions and resuscitation have been examined. Activation of lipid peroxidation and an increase in biogenic amine level, leading to marked hyperenzymemia, have been established. The activity of blood enzyme markers reflecting the severity of brain damage has been studied. It has been established that the more severe encephalopathy, the higher the activity of blood creatine phosphokinase. 2,3-cyclonucleotide-3-phosphohydrolase (CNPH), reflecting the damage of myelin membrane of nervous fibers, has been studied. The appearance of myelin-CNPH marker in the blood confirms demyelinization of the central nervous system (CNS). The more severe encephalopathy, the more marked the process of CNS demyelinization, the higher the activity of CNPH in the blood serum. The highest CNPH activity is observed in patients with eclampsia and in dead patients with postsystolic syndrome. PMID- 1862988 TI - [Analgesic transcutaneous electric nerve stimulation following surgery of the abdominal organs]. AB - The effect of continuous antinociceptive transcutaneous electrical neurostimulation (TENS) has been studied in 94 patients after abdominal surgery. The analysis of the clinical findings and sinus heart rhythm has demonstrated a strong enough analgesic effect of TENS, which was accompanied by a considerable, more than 4-fold, reduction in narcotic analgesics requirements, lower incidence of functional urination disturbances, intestinal paresis, retention of the regulating role of the autonomous nervous system, stable hemodynamics and on the whole a more smooth and safe course of the early postoperative period. PMID- 1862989 TI - [A cerebrospinal fluid fistula following spinal anesthesia]. PMID- 1862990 TI - [A method of cervical plexus anesthesia during surgery of the neck and its organs]. PMID- 1862991 TI - [Retrosternal novocaine blockade in the treatment of severe forms of bronchial asthma and status asthmaticus]. AB - Retrosternal procaine blockade with a 0.25% procaine solution, using a bent needle, 15-18 cm long, at the moment of bronchial asthma attack made it possible to arrest the attack in 25 patients, in 6 cases a considerable improvement of the patients' conditions was observed and in 4 patients there was no therapeutic effect. Retrosternal administration of 80-120 ml of a 0.25% procaine solution promotes to the improvement of respiration parameters, hemodynamics, blood gas composition. The procedure is simple and low traumatic. PMID- 1862993 TI - [Hyperbaric oxygenation and antioxidants in the complex intensive therapy of severe forms of pneumonia in children]. AB - Hyperbaric oxygenation (HBO) was used in a complex intensive therapy of 194 children, aged 3 days to 3 years, with severe pneumonias. Initially the patients have revealed intensification of free radical processes (FRP) with a simultaneous decrease in the level of enzyme and non-enzyme protection and a drastic increase in gluco- and mineralocorticoid adrenal function. HBO and antioxidants (unithiol and alpha-tocopherol) yielded excellent and good results (a drop in FRP level and activation of enzyme antioxidant protection) in 75.8% of patients. HBO was ineffective in 17% of cases, in 7.2% of patients signs of the developing oxygen intoxication have been revealed. Control over the indexes of erythrocytes resistance to peroxide, extra-erythrocyte hemoglobin, total peroxidase plasma activity during HBO procedure makes it possible to detect early preclinical signs of acute oxygen intoxication onset. PMID- 1862992 TI - [Technical difficulties of puncture and the functional anatomy of the subclavian vein]. AB - The difficulties occurring during puncture subclavian catheterization (PSC) are discussed. The results of 4559 PSC in 4007 patients are analysed. The results of ultrasonic examination (198 patients) and postmortem X-ray studies (34 cases) of the subclavian vein anatomy are presented. A great variability in the subclavian vein anatomy has been observed, this is associated with a likelihood of technical difficulties, failures and complications in standard PSC technique. An ultrasonic examination prior to PSC is recommended. PMID- 1862994 TI - [Hemosorption in the complex therapy of patients with poisonous snake bites]. AB - 14 hemosorption (HS) procedures have been performed in 6 patients after snake bites. The patients recovered after a few HS sessions. However small our experience is, it indicates high efficacy of HS in combination with other intensive care techniques in patients with snake bites and severe intoxication. PMID- 1862995 TI - [Correction of the immunologic shifts induced by hemosorption in sepsis of the newborn]. AB - Alongside with a positive clinical effect, hemosorption (HS) leads to the elimination of humoral immunity factors (Ig, FN) from the blood, having no effect on the phagocytic activity of leukocytes. Massive immunocorrection in doses 2-3 times higher than the age-matched ones, increases considerably the levels of IgG and FN. Immunomodulating effect of HS is enhanced when HS is combined with ultraviolet blood irradiation. PMID- 1862996 TI - [The possibility of normalizing the microcirculation using hemosorption in experimental peritonitis]. AB - The goal of the present paper was a comparative study of microcirculation in the peritoneum, mesentery and omentum during the development of experimental peritonitis, as well as the investigation of possible correction of microcirculatory disturbances with the help of hemosorption. It has been established that different degree of microcirculatory disturbances in the tissues under study depended on the duration of peritonitis. Hemosorption recovered microcirculation to initial values, which indicated the reversibility of the disturbances. PMID- 1862997 TI - [General anesthesia using calypsol during angiographic study of the extremities in children]. AB - In 17 children aged 7 to 14 years angiography of the extremities (AGE) was performed under general anesthesia by intravenous calypsol injection without premedication with cholinolytics (group I, monoanesthesia) or with premedication with atropine and neuroleptics (diazepam, droperidol; group II). It has been established that calypsol, in both groups, had a short-term moderate stimulating effect on the cardiac function and an insignificant effect on the respiratory function, which was not essential for the assessment of hemodynamic parameters during AGE. Muscle relaxation was more marked in children of group II, mainly due to the use of neuroleptics. In children of group II muscle relaxation was insignificant, this was associated with certain difficulties during AG. A technique of calypsol anesthesia during AGE in children has been elaborated, it is recommended to use calypsol in combination with neuroleptics, and to strengthen anesthesia by additional calypsol administration prior to the injection of contrast agents. PMID- 1862998 TI - [Pathogenesis and morphogenesis of acute pulmonary insufficiency during blood loss]. AB - Postmortem clinical and anatomic lung examinations in patients dead of blood loss and the experiments on animals have shown that pathological changes underlying acute pulmonary failure are to a great extent due to disorders in pulmonary hemodynamics associated with the spasm in the arterial and venous vascular bed of the respiratory zone. Durable spasm of pulmonary veins promotes to hydrostatic pressure elevation and the onset of pulmonary edema even after blood loss replacement. Massive infusion-transfusion therapy performed in pulmonary hemodynamic disorders may aggravate pulmonary edema and lead to the onset of acute pulmonary failure. PMID- 1862999 TI - [Synthetic analgesics of a new generation in present-day anesthesiology]. PMID- 1863000 TI - [Intrapleural anesthesia following thoracic surgery and in chest trauma]. AB - The analgesic effect of intrapleural administration of local anesthetics (lidocaine, trimecaine, azocaine) has been studied in 180 patients after thoracic surgery and with chest trauma. The effect was assessed on the basis of subjective (visual analogue 10-score scale) and objective findings (hemodynamic parameters, spirograms, ECG). In control patients analgesia was performed by intramuscular promedol administration. It has been shown that fractionated intrapleural administration of local anesthetics is an effective and safe analgesic technique after thoracic surgery and in chest trauma. PMID- 1863001 TI - Determinants of blood and body fluid exposure in a large teaching hospital: hazards of the intermittent intravenous procedure. AB - Determinants of staff exposure to blood and body fluids in a 1100-bed hospital were examined over a 2-year period. Eighty-two percent of the 799 reported accidental exposures were needlestick injuries, and 18% were cutaneous or mucous membrane splashes. Nurses and nursing students incurred 78.8% of the exposures; respiratory technologists and laboratory personnel, 9.2%; medical personnel, 7.5%; and support staff, 4.2%. Rate of exposure per 100,000 hours worked showed nursing students to be at particularly high risk, highlighting the need for specific instruction. Analysis of events leading to needlestick-related exposures revealed that the heparin lock intermittent intravenous procedure was involved in 26%; recapping accounted for 17%; improper disposal, 15%; manipulating equipment, 14%; phlebotomy, 12%; and other needlestick events, 16%. Ocular splashes and spills onto nonintact skin each accounted for 50% of the total number of non needlestick-related exposures. This study revealed the hazardous nature of the intermittent intravenous procedure, prompting specific revisions in this procedure as well as promoting point-of-use sharps disposal and other preventive measures. PMID- 1863003 TI - Transmural surgical gown pressure measurements in the operating theater. AB - Transmural gown pressures encountered when the surgeon comes into contact with a patient were measured in the operating theater. The surgical gown industry has assumed these pressures to be less than 5 psi in testing the efficacy of the gown and drape barrier material to impede bacterial transmission through its pores. In this study, pressure-sensitive contact film and resistive strain gauge recordings made from the surgeon's abdominal region and forearms indicated peak contact pressures in excess of 60 psi. This report indicates a need to reassess the basis of test utilization in evaluating barrier materials used in gowns and drapes. PMID- 1863002 TI - Prevention of catheter-associated bacteriuria: clinical trial of methods to block three known pathways of infection. AB - The simultaneous use of methods to block all three known pathways of bacterial entry into the bladders of catheterized patients has been suggested because of the limited effectiveness of individual methods that block single pathways. We conducted a randomized controlled trial to assess the prevention of bacteriuria in patients, using a three-way system that included a hydrophilic polymer-coated and preconnected sealed catheter system, daily catheter care, and disinfection of the outflow tube of the drainage bag with povidone-iodine (i.e., methods to block bacterial entry at the urethral insertion site, at the catheter drainage tube junction, and at the outflow tube). Among treated patients, 14 (4.7%) of 300 acquired bacteriuria as compared with 15 (4.9%) of 306 who did not receive the protocol treatments. Only 3 of 29 episodes of bacteriuria occurred in patients whose meatal cultures did not contain gram-negative bacilli or enterococci; thus migration of bacteria in the periurethral mucous sheath appeared to be the most common pathway by which bacteria gained entry into the bladder in this study. Catheter care and disinfection of the drainage bag outflow tube as used in this study remain unproven methods of preventing catheter-associated bacteriuria. Preconnected catheters with junction seals were used in both treated and untreated patients and, on the basis of previous studies, appear to be effective in reducing junction disconnections and bacteriuria. Therefore we conclude that the use of several simultaneous measures to prevent catheter-associated urinary infections is no more effective than the use of preconnected catheters with junction seals alone and is clearly more expensive. PMID- 1863004 TI - An outbreak of scabies in a New York City jail. PMID- 1863005 TI - Surveillance and control of antibiotic use in the hospital. PMID- 1863006 TI - Definitions of infections. PMID- 1863007 TI - Agenda for change. PMID- 1863008 TI - Is it the gown or the precautions in its use? PMID- 1863009 TI - The HIV challenge. PMID- 1863010 TI - Physical training and antiplatelet treatment in stage II peripheral arterial occlusive disease: alone or combined? AB - The efficacy of physical training alone or combined with antiplatelet therapy (dipyridamole and aspirin) was studied in 30 patients with stage II peripheral arterial occlusive disease (PAOD). Patients were randomly allocated to one of the following groups: Group A--dipyridamole 75 mg three times daily and aspirin 330 mg once daily: Group B--physical exercise; Group C--physical exercise and dipyridamole 75 mg three time daily and aspirin 330 mg once daily. After six months' treatment the pain-free walking time (PFWT) and the maximum walking time (MWT) improved significantly (p less than 0.05) in all three groups. In group A the PFWT lengthened by 35% (from 101.00 +/- 34.56 to 137.32 +/- 40.50 s) and the MWT by 38% (from 150.34 +/- 55.60 to 207.26 +/- 60.67 s); in group B the PFWT lengthened by 90% (from 90.65 +/- 40.54 to 171.45 +/- 55.60 s) and the MWT by 86% (from 145.39 +/- 60.50 to 270.63 +/- 63.61 s). When physical exercise was associated with drugs as in group C, the PFWT lengthened by 120% (from 89.51 +/- 43.89 to 196.72 +/- 51.73 s) and the MWT by 105% (from 160.43 +/- 59.84 to 329.05 +/- 63.96 s). No significant variations were observed at any stage of the study in the ankle/arm pressure ratio at rest and after standard treadmill exercise, in the plethysmographic rest and peak flows, or in the transcutaneous oxygen pressure in basal conditions and in its half recovery time after an induced ischemia. The results confirm the benefits of regular exercise in stage II PAOD patients but suggest they may be enhanced by antiplatelet therapy. PMID- 1863011 TI - Venous thrombosis after long-term transvenous pacing in the Chinese. AB - To determine the incidence of venous thrombosis after long-term transvenous pacing in the Chinese, venograms were performed in 50 consecutive Chinese patients seen at the pacemaker clinic. There were 25 women and 25 men. The mean age was sixty-six years (range thirty-two to eighty-one). The indications for pacing were complete heart block in 16 patients and sick sinus syndrome in the remainder. All pacemakers were of the single-chamber ventricular pacing type and had been implanted for a mean period of four years (range two to seven). In 27 patients the route of entry for the pacing electrode was through the cephalic vein and in the other 23 patients the subclavian veins were used. Of the 50 venograms, 1 showed partial and 1 showed total obstruction at the subclavian vein. Both patients (4%) were asymptomatic. All others (96%) were normal. The incidence of venous thrombosis was not related to the routes of entry of the pacing electrodes. All patients tolerated the procedure well and had no complications. It is concluded that the incidence of venous thrombosis after long term transvenous pacing is extremely low in the Chinese (4%), and venograms are both safe and useful for identifying venous thrombosis related to transvenous pacing. PMID- 1863012 TI - Emergency arteriography in the assessment of penetrating trauma to the lower limbs. AB - One hundred emergency arteriographies (EA) were performed in 87 patients with lower limb trauma due to high-velocity missiles. Thirteen patients had bilateral injuries. In 79 cases, EA findings were positive and led to emergency surgery. In 76 cases an arterial injury was found and treated, a positive predictive value of 96% (76/79). In the other 3 cases, no arterial lesion was found (3 false positives). Among the 21 patients with normal findings from angiography, 10 had surgical exploration because of high clinical suspicion of vascular injury. Arterial injury was found in 2 cases (2 false negatives). In 8 patients, arteriography modified the surgical procedure. In the 11 remaining patients, clinical and echo Doppler follow-up results were normal, a negative predictive value of 90% (19/21). Sensitivity was 97%, specificity 86%, and accuracy 95%. These data show that arteriography in stable patients is a safe and accurate procedure. It permits avoidance of unnecessary surgical exploration in selected patients and helps modify the surgical procedure. PMID- 1863013 TI - Compression therapy of limb edema using hydrostatic pressure of mercury. AB - A new apparatus for the treatment of edema of the extremities is described. The extremity is placed in a cylindrical vertical tank and isolated by a circumferential synthetic rubber membrane. The equipment is programmed to create a mold of the extremity using a slurry of plastic granules from a reservoir. Mercury is then pumped between the mold and the extremity, thereby exerting a pressure gradient on the extremity equal to the hydrostatic pressure of the mercury column. A computerized program forms the mold and runs several compression cycles for each treatment session. Twelve patients were treated (8 upper extremities, 4 lower extremities) on a weekly or semiweekly basis. Progress was followed with computed axial tomography scans, as well as measurements and photographs. Ten patients experienced significant immediate decrease in edema with each treatment. Wrapping or elastic support was required to prevent the return of edema between treatments. No pain, skin injury, or other complication of treatment was noted. The apparatus can safely provide short-term, immediate, significant improvement of extremity edema. Further studies will be necessary to determine long-term benefit. PMID- 1863014 TI - Effect of blood glucose level in acute cerebral ischemia in spontaneously hypertensive rats--survival and brain pathology. AB - The present study was designed to examine the effect of blood glucose level on survival and pathologic changes of the cortical neuronal cells during and after three-hour incomplete cerebral ischemia, which was induced by bilateral carotid artery ligation in spontaneously hypertensive rats (SHRs). Blood glucose levels were varied by intraperitoneal infusion of 50% glucose (hyperglycemia) or insulin with hypertonic saline (hypoglycemia) or hypertonic saline (normoglycemia). None of the hyperglycemic or normoglycemic animals died during three-hour ischemia, whereas 45% of hypoglycemic animals died (p greater than 0.001). The survival rate for twenty-four hours after recirculation was in the following ascending order: hypoglycemia, normoglycemia, and hyperglycemia. Neither hypoglycemia nor hyperglycemia (38-392 mg/dL) in nonischemic animals developed any morphologic changes in the cerebral cortex. However, both the ischemic and recirculated brains showed various degrees of histologic changes such as shrinkage of the neuronal cells with cytoplasmic vacuoles, perineuronal edema, and swelling of neuropils. Such ischemic damage of the brain was more marked in hypoglycemic animals than in hyperglycemic or normoglycemic ones during ischemia, as well as one hour after recirculation. The results suggest that cerebral ischemia and its outcome become more deleterious in hypoglycemic than in normoglycemic and hyperglycemic states. On the other hand, hyperglycemia is not necessarily a disadvantage in acute cerebral ischemia with or without reperfusion in this model. PMID- 1863015 TI - The role of two-dimensional echocardiology in the diagnosis of infective endocarditis [corrected]. AB - Two-dimensional echocardiography has had a significant impact on and is considered the technique of choice for the diagnosis and management of infective endocarditis. Over a thirty-six month period, 106 patients were evaluated by echocardiography for the possibility of endocarditis. The diagnosis of endocarditis was determined by strict clinical and laboratory criteria. All clinical histories, blood cultures, echocardiograms, and autopsy results were reviewed. Five echocardiograms were technically inadequate, resulting in a study population of 101 patients. The age of the patients ranged from forty-five days to eighty-eight years (mean fifty-seven years). The clinical manifestations of endocarditis included fever (83%), chills (60%), congestive heart failure (25%), and splenomegaly (18%). Twelve patients had preexisting valvular or congenital heart disease. Gram-positive cocci were the most common microorganisms. Complications included mitral regurgitation, subarachnoid hemorrhage, renal infarction, stroke, and a pulmonary embolus. The patients were divided into two groups: Group I consisted of 36 patients with definite vegetations by echocardiography, and Group II had 65 patients with no vegetations. In Group I, acute infective endocarditis was present in 35 patients, whereas only 4 patients had endocarditis in Group II. The sensitivity of two-dimensional echocardiography for detecting endocarditis was 90%. The specificity was 98%. The predictive accuracy for a positive test was 97%, and the predictive accuracy for a negative test was 94%. Thus, two-dimensional echocardiography appears to have a high sensitivity, specificity, and predictive value in the evaluation of patients with suspected endocarditis. PMID- 1863016 TI - Effects of cocaine on canines' coronary arteries. AB - Nine canines were anesthetized with pentobarbital and studied by both selective and semiselective coronary artery angiography following intravenous bolus doses of 1,3,5,8, or 10 mg/kg of cocaine. Catheterization was accomplished with a 5 Fr catheter over a 0.035 inch guidewire under fluoroscopic control, and angiograms were obtained by injection of a diatrizoate solution. Digital subtraction angiography (DSA) was performed prior to cocaine administration and at minutes 0.5, 1, 1.5, 3, 5, and, in some cases, minutes 10 and 15 after cocaine administration. The 1 and 3 mg/kg doses of cocaine had no effect on the coronary arteries. The 5 mg/kg dose significantly dilated the coronary arteries. The 8 mg/kg dose produced significant dilation at 30 seconds after cocaine but nonsignificant dilation of the coronary arteries at all other times. The 10 mg/kg dose produced significant dilation at 30 seconds, nonsignificant dilation at 60 seconds followed by significant constriction at 90 seconds after cocaine, which led to immediate death in most animals. The coronary dilation and constriction produced by 10 mg/kg of cocaine could be prevented by either preadministration or postadministration of naloxone, but this did not prevent subsequent death. PMID- 1863017 TI - Vasculitic skin ulcers associated with myelofibrosis--a case report. AB - This is the case report of a seventy-seven-year-old woman with ulcerated skin vasculitis of the lower extremities that preceded the appearance of myelofibrosis. No previous report of this association has been found in a survey of the literature. PMID- 1863018 TI - Mycotic aortic aneurysm infected by Clostridium septicum--a case history. AB - The authors describe a sixty-seven-year-old hypertensive, diabetic man with a mycotic abdominal aortic aneurysm infected with Clostridium septicum. The patient had colonic polyps but no malignant disease. They could find only one other report of a mycotic aneurysm infected with C. septicum. In that case, as in most other cases of C. septicum bacteremia, the patient had gastrointestinal cancer. Their case suggests that treatment for a clostridial infection should be considered in patients with known gastrointestinal disease, signs and symptoms of sepsis, and abdominal pain. Conversely, patients known to have a C. septicum infection should be evaluated for gastrointestinal lesions. PMID- 1863020 TI - The objectivity and subjectivity of mitral valve prolapse. PMID- 1863019 TI - Splenic vein aneurysm: MR appearance--a case report. AB - A presumed pancreatic head mass by non-contrast CT examination, was proven to be a splenic vein aneurysm by enhanced CT, MRI, sonography and arteriography. Dangerous percutaneous aspiration was avoided. PMID- 1863021 TI - Antiarrhythmic proarrhythmias. PMID- 1863022 TI - Timing of breast cancer excision during the menstrual cycle influences duration of disease-free survival. AB - OBJECTIVE: To study disease-free survival at 10 years in relation to timing of breast tumor excision during the menstrual cycle. DESIGN: A prospective study of consecutively treated patients with primary breast cancer. SETTING: Memorial Sloan-Kettering Cancer Center, New York. PATIENTS: Two hundred and eighty-three premenopausal patients treated by mastectomy and axillary dissection. MAIN RESULTS: When the tumor was excised during the follicular phase, approximated by setting the putative day of ovulation on day 14 after the onset of last menses, a higher recurrence risk (43%) was observed compared with excision later in the menstrual cycle (29%, P = 0.02). The rate peaked among patients treated between days 7 and 14 and was lowest between days 20 and 30. Multivariate analysis using the Cox regression model to control for tumor size, nodal status, estrogen receptor status, adjuvant chemotherapy, and family history indicated that the hazard rate of breast cancer recurrence after excision during the follicular phase was 1.53 (95% Cl, 1.02 to 2.29). Stratification by nodal status indicated that the effect of phase was statistically significant only among patients with positive nodes (hazard ratio, 2.10; Cl, 1.19 to 3.70). CONCLUSIONS: Our results support the hypothesis that the risk for recurrence may be affected by the hormonal milieu of the menstrual cycle; these findings must be confirmed, however, by a prospective study in which cycle phase at time of tumor excision is biochemically documented. PMID- 1863023 TI - Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. AB - OBJECTIVE: To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival. DESIGN: Registry with prospective follow-up. SETTING: Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart, Lung, and Blood Institute. PATIENTS: Patients (194) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988. MEASUREMENTS: At diagnosis, measurements of hemodynamic variables, pulmonary function, and gas exchange variables were taken in addition to information on demographic variables, medical history, and life-style. Patients were followed for survival at 6-month intervals. MAIN RESULTS: The estimated median survival of these patients was 2.8 years (95% Cl, 1.9 to 3.7 years). Estimated single-year survival rates were as follows: at 1 year, 68% (Cl, 61% to 75%); at 3 years, 48% (Cl, 41% to 55%); and at 5 years, 34% (Cl, 24% to 44%). Variables associated with poor survival included a New York Heart Association (NYHA) functional class of III or IV, presence of Raynaud phenomenon, elevated mean right atrial pressure, elevated mean pulmonary artery pressure, decreased cardiac index, and decreased diffusing capacity for carbon monoxide (DLCO). Drug therapy at entry or discharge was not associated with survival duration. CONCLUSIONS: Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index. Such an equation, once validated prospectively, could be used as an adjunct in planning treatment strategies and allocating medical resources. PMID- 1863024 TI - Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis. A multicenter study. AB - OBJECTIVE: To evaluate the efficacy and safety of a pH-sensitive, polymer-coated oral preparation of mesalamine in patients with mildly to moderately active ulcerative colitis. DESIGN: A multicenter, double-blind, placebo-controlled randomized trial. SETTING: Five university-based medical centers, one inflammatory bowel disease center, and three private practice sites. PATIENTS: A total of 158 patients with newly or previously diagnosed active ulcerative colitis. INTERVENTION: A pH-sensitive, polymer-coated oral preparation of mesalamine (5-aminosalicylic acid) was used at 1.6 and 2.4 g/d for 6 weeks. MEASUREMENTS: Efficacy was measured by scores for stool frequency, rectal bleeding, patient's functional assessment, sigmoidoscopic findings, and physician's global assessment. Stringent criteria for disease activity were established prospectively. RESULTS: The analysis of protocol-compliant patients showed a significant improvement at 3 weeks in patients taking 2.4 g/d of mesalamine compared with patients taking placebo (32% versus 9%; P = 0.003). At 6 weeks, both the 1.6 g/d (43%) and 2.4 g/d (49%) doses were significantly superior to placebo (23%) (P = 0.03 and P = 0.003, respectively). In addition, more patients worsened in the placebo group compared with the 2.4 g/d group (50% versus 19%; P = 0.003); however, there was no statistically significant difference in worsening between the 1.6 g/d mesalamine group and the placebo group. The oral mesalamine tablet was well tolerated, and no clinically significant changes were observed in hematologic, hepatic, or renal laboratory profiles. CONCLUSION: Colon-targeted oral mesalamine at 2.4 g/d is effective therapy for mildly to moderately active ulcerative colitis. It is well tolerated and should provide a viable therapeutic alternative to sulfasalazine. PMID- 1863025 TI - Are history and physical examination a good screening test for sleep apnea? AB - OBJECTIVE: To determine whether presenting clinical history, pharyngeal examination, and the overall subjective impression of the clinician could serve as a sensitive screening test for sleep apnea. DESIGN: Blinded comparison of history and physical examination with results of nocturnal polysomnography. SETTING: Sleep clinic of a tertiary referral center. PATIENTS: A total of 410 patients referred for suspected sleep apnea syndrome. Most patients reported snoring. MEASUREMENTS: All patients were asked standard questions and given an examination relevant to the diagnosis of the sleep apnea syndrome, and all had full nocturnal polysomnography. Patients with more than ten episodes of apnea or hypopnea per hour of sleep were classified as having sleep apnea. Stepwise linear logistic regression was used to develop two predictive models of sleep apnea: one based on the presence of characteristic clinical features, age, sex, and body mass index; and one based on subjective clinical impression. RESULTS: The prevalence of sleep apnea in our patients was 46%. Only age, body mass index, male sex, and snoring were found to be predictors of sleep apnea. The logistic rule discriminated between patients with and without sleep apnea (receiver operating characteristic [ROC] area, 0.77 [95% Cl, 0.73 to 0.82]). For patients with a predicted probability of apnea of less than 20%, the clinical model had 94% sensitivity and 28% specificity. Subjective impression alone identified correctly only 52% of patients with sleep apnea and had a specificity of 70%. CONCLUSIONS: In patients with a high predicted probability of the sleep apnea syndrome, subjective impression alone or any combination of clinical features cannot serve as a reliable screening test. However, in patients with a low predicted probability of sleep apnea, the model based on clinical data was sufficiently sensitive to permit about a 30% reduction in the number of unnecessary sleep studies. PMID- 1863026 TI - Loop diuretics for chronic renal insufficiency: a continuous infusion is more efficacious than bolus therapy. AB - OBJECTIVE: To test the hypothesis that a continuous, low-dose infusion of a loop diuretic is more efficacious and better tolerated than conventional intermittent bolus therapy in patients with severe chronic renal insufficiency (CRI). DESIGN: Randomized, crossover clinical trial with subjects serving as their own controls. SETTING: The General Clinical Research Center of Indiana University Hospital, Indianapolis, Indiana. PATIENTS: Eight adult volunteers with severe stable CRI (mean creatinine clearance, 0.28 mL/s; range, 0.15 to 0.47 mL/s) were recruited from the outpatient nephrology clinics of Indiana University Medical Center. INTERVENTIONS: On admission, diuretic drugs were withdrawn and patients were equilibrated on an 80 mmol/d sodium, 60 mmol/d potassium metabolic diet. Patients were randomized to receive a 12-mg intravenous dose of bumetanide given either as two 6-mg bolus doses separated by 6 hours or as the same total dose administered as a 12-hour continuous infusion. When sodium balance was re-established, each patient was crossed over to the alternative study limb. All patients completed both phases of the study. MEASUREMENTS AND RESULTS: Comparable amounts of bumetanide appeared in the urine during the study period (infusion, 912 +/- 428 micrograms; bolus, 944 +/- 421 micrograms; difference, 32 micrograms; 95% CI, -16 micrograms to 80 micrograms, P = 0.16). The continuous infusion resulted in significantly greater net sodium excretion (infusion, 236 +/- 77 mmol; bolus, 188 +/- 50 mmol; difference, 48 mmol; CI, 16 mmol to 80 mmol, P = 0.01). No patient had episodes of drug-induced myalgias during the continuous infusion compared with 3 of 8 patients with bolus therapy. CONCLUSIONS: In patients with severe CRI, a continuous intravenous infusion of bumetanide is more effective and less toxic than conventional intermittent bolus therapy. Continuous administration will probably be useful in patients with severe CRI who have not achieved an adequate natriuresis or who show evidence of drug toxicity with standard diuretic dosing regimens. A similar benefit may occur in selected diuretic-resistant patients with cardiac or hepatic disease, and studies in these patients seem warranted. PMID- 1863027 TI - Cardiac lymphoma in a patient with AIDS. PMID- 1863028 TI - A phenomenology of scut. AB - OBJECTIVE: To identify, describe, and quantify the night-call duties that residents in internal medicine call "scutwork" and to compare faculty and residents' perceptions of scutwork. DESIGN: Prospective, cross-sectional study. SETTING: General internal medicine training program at a university-affiliated tertiary care hospital. PARTICIPANTS: Forty-eight residents who spent 3 months or more on an internal medicine teaching unit during the previous year and 41 faculty members who spent 2 months or more on one of these units. INTERVENTIONS: Postcall surveys and night-call diaries were used to analyze residents' activities, to derive a definition of scutwork, and to estimate its prevalence. Residents and faculty then completed a detailed questionnaire that included ratings of the educational value, "scut content," and residents' responsibility for 20 specific tasks. MAIN RESULTS: Eighty-three percent of residents found scutwork and education to be mutually exclusive for the 20 tasks, although 20% indicated that scutwork was an appropriate task for residents. Residents' ratings of tasks as scut varied according to the context of the task. For example, obtaining routine consent from someone else's patient was considered scutwork by 98% of residents, whereas obtaining such consent from the residents's own patient was rated as scutwork by only 52% (P less than 0.01). Similarly, performing intravenous cannulation at the request of ward staff was rated as scut by 94% of residents, whereas performing cannulation at another resident's request was rated as scut by 56% (P less than 0.01). Night-time admission of a patient for an elective procedure was rated as scut by 75% of residents, whereas admission of such a patient after discussion with a faculty member was labeled scut by only 44% (P less than 0.01). Faculty ratings of such admissions did not show the same variation (24% for both). Faculty were more likely than residents to assess tasks as educational (50% compared with 26%, P less than 0.01) but were less likely to consider tasks as scutwork (47% compared with 62%, P = 0.12) or as work that should be done by nonresidents (35% compared with 46%, P greater than 0.2). CONCLUSIONS: Our results suggest that the characteristics of scutwork can be identified, that the perception of scut varies between faculty and residents, and that the context of a task often determines whether residents perceive it as scut. PMID- 1863029 TI - Hemodynamic determinants of exercise capacity in chronic heart failure. AB - PURPOSE: To synthesize information on hemodynamic determinants of exercise capacity in patients with chronic heart failure. DATA IDENTIFICATION: Relevant studies published from the mid-1960s to the present were identified by a manual search of the English-language literature and by bibliographic review of pertinent articles. STUDY SELECTION: Both controlled and observational studies that reported measures of either exercise time or oxygen uptake and hemodynamic variables in patients with heart failure were reviewed for quality and included when relevant to the discussion. DATA EXTRACTION: Key conclusions or data, or both, were extracted from each article and described. DATA SYNTHESIS: Exercise intolerance is a hallmark of chronic congestive heart failure. Studies have emphasized central factors and indices of systolic ventricular function, but poor relations have been consistently found between these measurements and exercise capacity. Recent data suggest that diastolic function (that is, ventricular filling and compliance) is an important factor affecting the ability to increase cardiac output and determining exercise capacity, but this issue needs further study. A clearer picture of histologic and biochemical abnormalities in skeletal muscle has recently emerged; patients with heart failure show greater glycolysis, reduced oxidative phosphorylation, and reduced oxidative enzyme activity. Vasodilatory abnormalities in heart failure were first described more than 20 years ago, and such abnormalities may underlie recently reported reductions in skeletal muscle blood flow during exercise. Relative hyperventilation is commonly observed during exercise in patients with heart failure and is related to ventilation-perfusion mismatching in the lung due to a higher-than-normal fraction of physiologic dead space. Neurohumoral abnormalities include reductions in beta-receptor density and sensitivity and contribute to reduced inotropic and chronotropic responses to exercise. CONCLUSIONS: Systolic function and exercise capacity are unrelated in patients with chronic heart failure, but many hemodynamic abnormalities (including those in the heart, lung, and skeletal muscle) overlap, which leads to exercise intolerance in these patients. PMID- 1863030 TI - Comparison of the quality of ambulatory care for fee-for-service and prepaid patients. AB - OBJECTIVE: To determine whether the quality of care for common ambulatory conditions is adversely affected when physicians are provided with incentives to limit the use of health services. DESIGN: Retrospective cohort study over a 2 year period. SETTING: Four group practices that cared for both fee-for-service patients and prepaid patients within a network model health maintenance organization (HMO). PATIENTS: Equal numbers of prepaid (HMO) and fee-for-service patients were selected by randomly choosing medical records from each group practice: 246 patients with chronic uncomplicated hypertension and 250 women without chronic diseases who received preventive care. MAIN OUTCOME MEASURES: Adequate hypertension control was defined as a mean blood pressure of less than 150/90. Adequate preventive care was defined as the provision of blood pressure screening, colon cancer screening, breast cancer screening, and cervical cancer screening within guidelines recommended by the 1989 U.S. Preventive Services Task Force. Resource use was measured by the annual number of visits and tests. MAIN RESULTS: The adjusted relative odds of HMO patients having controlled hypertension, compared with fee-for-service patients, were 1.82 (95% CI, 1.02 to 3.27). The relative risks of HMO patients receiving preventive care within established guidelines were 1.19 (CI, 0.93 to 1.51) for colon cancer screening, 1.78 (CI, 1.11 to 2.84) for annual breast examinations, 1.75 (CI, 1.08 to 2.84) for biannual mammography, and 1.35 (CI, 1.13 to 1.60) for Papanicolaou smears every 3 years. Prepaid patients had visit rates that were 18% to 22% higher than those of fee-for-service patients. CONCLUSIONS: In the type of network model HMO we studied, the quality and quantity of ambulatory care for HMO patients was equal to or better than that for fee-for-service patients. In this setting, the incentives for physicians to limit resource use may be offset by lack of disincentives for HMO patients to seek care. PMID- 1863031 TI - The optimal timing of mastectomy: low tide or high tide? PMID- 1863032 TI - Law, medicine, and the "gag rule". PMID- 1863033 TI - Preventive care guidelines. PMID- 1863034 TI - Diuretic resistance versus adaptation. PMID- 1863036 TI - Lawyer's advice. PMID- 1863035 TI - Disopyramide and inducible arrhythmias. PMID- 1863037 TI - "Misconceptions" about AIDS. PMID- 1863038 TI - The dosage of dilute lignocaine for the infiltration technique of local analgesia. AB - The maximum dose of plain lignocaine is the subject of debate. The manufacturers recommend 200 mg in the 'adult' and clinicians often use up to 500 mg or more. One way of settling the issue is to determine serum concentrations of free lignocaine, in the absence of which recommendations are based on clinical experience. For the infiltration technique of local analgesia 500 mg is a safe maximum for plain lignocaine and 670 mg with adrenaline. These higher dosages are recommended only for dilute solutions such as 0.4% and 0.5% lignocaine. The 0.2% solution can permit the use of even higher dosages. A discussion of serum concentrations indicates that these recommendations are within acceptable limits. Concentrated 1% and 2% solutions should not be used for the infiltration technique. PMID- 1863039 TI - A comparative study between Michel and Proximate clips for the closure of neck incisions. AB - A prospective study comparing two types of surgical clip, the Proximate II (Ethicon) staple and the Michel clip, was performed on 30 thyroidectomy (horizontal) and 50 carotid endarterectomy (vertical) incisions with reference to their ease of handling, patient comfort, complication rate, cosmetic result and cost. In each patient half of the wound was approximated with one type of clip and half with the other. The Proximate II staple was more comfortable for the patient in the vertical wounds (P less than 0.02), easier to remove as judged by the nurse in both horizontal (P less than 0.001) and vertical (P less than 0.02) wounds, and by the patient in the horizontal wounds (P less than 0.02) only. The incidence of inflammation was significantly higher with the Michel clip (P less than 0.001). In both the horizontal (P less than 0.05) and the vertical (P less than 0.001) wounds, when the scar was assessed at the time of discharge from hospital, the Proximate II staple achieved a significantly better result. However, assessment of the wounds by patient and researcher 6 weeks postoperatively, revealed no significant difference between the wounds with regard to cosmetic outcome. The Proximate II design, however, costs between seven and ten times more than the Michel clip depending on the size of the dispenser used, and since the late cosmetic result offers no advantage over the latter design, we feel these financial variables deserve consideration. PMID- 1863040 TI - Peak expiratory flow in the detection of retrosternal goitre. AB - In 24 patients where the lower border of a cervical goitre was poorly defined, the value of simple lung function tests in the prediction of the presence of a retrosternal goitre was assessed. At operation there were nine patients with retrosternal extension (Group I) and 15 without (Group II). The preoperative PEF ratio (observed to predicted) was significantly different between the two groups (P = 0.004) with a positive predictive value of 90% for a retrosternal goitre. This difference was abolished after thyroidectomy. There was a significant improvement in PEF in patients with retrosternal goitres after thyroidectomy (P less than 0.001). It is concluded that the preoperative measurement of PEF is a simple method of detecting the retrosternal extension of a cervical goitre. PMID- 1863041 TI - Audit of attitudes to and use of postoperative thromboembolic prophylaxis in a regional health authority. AB - A survey of usage and attitudes to thromboembolic prophylaxis among 46 general surgeons in the Mersey Region found that 87% use either low-dose heparin, graduated compression stockings or both on a regular basis for their major cases. However, there was a wide variation of usage: 9 (19.6%) always used heparin in combination with thromboembolic stockings, 4 (8.7%) always used heparin alone, no surgeon used thromboembolic stockings alone. A total of 18 (39%) used thromboembolic stockings in combination with heparin, one-half of them selectively. A further 24% of surgeons used either low-dose heparin or thromboembolic stockings or both on selected patients. Current literature beliefs concerning the efficacy of low-dose heparin and thromboembolic stockings showed a similar variation, with 13% of surgeons believing that the efficacy of low-dose heparin against postoperative deep vein thrombosis has not been shown, 22% believing that thromboembolic stockings were ineffective against postoperative deep vein thrombosis, and 24% believing that low-dose heparin was of no value as a prophylactic agent against postoperative pulmonary embolism. Published meta analysis has shown these beliefs to be wrong. PMID- 1863042 TI - The varicose vein waiting list: results of a validation exercise. AB - A lengthening waiting list for treatment of varicose veins in a busy teaching hospital prompted a careful review. Patients were sent a detailed questionnaire which addressed current symptoms, progression of the complaint and the desire for surgical treatment. Of 519 patients on the waiting list, replies were received from 471 (91%). Forty-eight patients could not be traced after two questionnaires had been sent and enquiries made with their last known local GP. A further 87 (17%) patients were removed from the waiting list because they no longer desired treatment or had had treatment in the private sector. The remaining 384 patients were sent appointments for specially organised Saturday morning assessment clinics attended by consultants and senior registrars. Eighty patients failed to attend without giving a reason and were removed from the waiting list. Of 304 patients reviewed, surgical treatment was considered necessary for 219, of whom 182 were suitable for day-case surgery, leaving only 37 patients of the original 519 who required inpatient surgical care. This study has shown how careful assessment and the increased provision of day-case facilities can relieve pressure on inpatient care. PMID- 1863043 TI - Ultrasound guided subclavian vein catheterisation. PMID- 1863044 TI - Retrocolic pelvic omentoplasty in abdominoperineal excision of the rectum. AB - A series of 53 patients underwent abdominoperineal excision of the rectum, 25 by the conventional method and 28 using retrocolic pelvic omentoplasty without drains. There were no differences in age, sex ratios, indications for surgery, stage of cancer and preoperative haemoglobin. There were no differences in the incidence of postoperative abdominal complications (wound dehiscence, obstruction and bleeding) between the two groups. However, patients undergoing omentoplasty without drainage stayed in hospital for a significantly shorter period (median of 16 days compared to 24 days) and benefited from far faster primary healing of the perineum (median of 20 days vs 133 days). It is concluded that retrocolic pelvic omentoplasty without drainage results in shortened postoperative hospital stay and promotes primary perineal healing after abdominoperineal excision of the rectum. PMID- 1863045 TI - The incidence and value of rectal examination in children with suspected appendicitis. AB - Rectal examination is considered an important part of the examination of patients presenting with abdominal pain. However, children find anal digitation unpleasant and it was our impression that doctors were becoming less insistent on performing a rectal examination. We performed an audit of rectal examination and assessed whether this made any difference to the management of children with acute abdominal pain. We looked at the records of 48 children from 1989 and 49 children from 1985 presenting with abdominal pain. We found that the rate of rectal examination was halved in this time. Diagnostic accuracy was similar in the two groups, and the morbidity rate was the same. These findings call into question the need for routine rectal examination in children with suspected appendicitis. PMID- 1863046 TI - Efficiency of blood use and prospects for autologous transfusion in general surgery. AB - A 6-month retrospective audit of crossmatch and transfusion practice in a general surgical unit has been performed. Inefficiencies in blood ordering practices have been demonstrated and the value of performing a local audit to allow estimation of blood needs has been proven. Using criteria based on the suggested tariff for operations derived from this audit, only a small number of general surgical patients would be considered as potential autologous blood donors. PMID- 1863047 TI - Cutaneous malignant melanoma: audit of the diagnostic process. AB - The results of a study of the diagnostic process in 202 cutaneous malignant melanomas over a 5-year period in one region are presented. Patient delay of more than 3 months was noted in at least 60% of cases, and delay after presentation was identified in 21% of the case histories. In 12% of the cases an opportunity for earlier diagnosis had been missed. The factors leading to delay in diagnosis are highlighted and the need for the dissemination of information relating to the early stages of the disease is emphasised. PMID- 1863048 TI - The management of popliteal aneurysm: the importance of early surgical repair. AB - A total of 58 popliteal aneurysms were found in 40 patients presenting between June 1982 and May 1989. Of these, 51 were caused by atherosclerosis, and there were five post-stenotic aneurysms associated with entrapment, one mycotic and one post-traumatic aneurysm. There were 18 patients with bilateral aneurysms, and two others had the first side repaired elsewhere before referral to this hospital. Aneurysms were found at other sites in 16 patients. Urgent treatment was needed for 32 patients (80%). Two required streptokinase treatment to clear arteries distally. Three needed fasciotomy for compartment syndrome. Two patients had above-knee amputation. Of 36 urgent operations, 13 had postoperative complications (36%). Four grafts were later revised successfully. At mean follow up of 23 months (range 3-96 months), three patients had claudication secondary to preoperative distal arterial occlusion, and one patient had residual mild foot drop. These operative results contrast sharply with the low complication rate after elective operation for popliteal aneurysm. In these patients, 14 asymptomatic aneurysms were repaired uneventfully. Four patients who did not undergo elective operation later developed acute thrombosis (3) and rupture (1). This experience supports our policy that early elective treatment for popliteal artery aneurysm is the most appropriate choice. PMID- 1863049 TI - Ventilation with isoflurane in the Triservice anaesthetic apparatus: a comparison with halothane and trichlorethylene. AB - Recovery from anaesthesia using the Triservice anaesthetic apparatus with either isoflurane alone or halothane and trichlorethylene, was assessed by measurement of reaction time. There was no statistically significant improvement in recovery between patients who received low concentrations of isoflurane and those who received halothane and trichlorethylene. The mean profiles of systolic pressure and heart rate were significantly greater in the isoflurane group (P less than 0.05) than in the halothane/trichlorethylene group. Cardiovascular stability was maintained into the recovery period. The benefits of low concentrations of isoflurane as sole agent in the Triservice anaesthetic apparatus and their extrapolation to a shocked casualty in a military setting are discussed. PMID- 1863050 TI - Primary restorative colectomy in malignant left-sided large bowel obstruction. PMID- 1863051 TI - Treatment of carcinoma of the esophagus. PMID- 1863052 TI - The role of reconstructive surgery in the management of war wounds. PMID- 1863053 TI - Deaths following trauma: an audit of performance. PMID- 1863054 TI - An improved nipple prosthesis. PMID- 1863055 TI - Two kinds of diverticular disease. PMID- 1863056 TI - A retractor for cholecystectomy. PMID- 1863057 TI - Dilemmas facing surgical research in the '90s. AB - Surgical research in the '90s will need to address several general problems. This paper discusses the role of informed consent in clinical trials, animal experimentation in surgical research, and the importance of research in both undergraduate and postgraduate education. PMID- 1863058 TI - Surgical workload: variation in throughput. PMID- 1863059 TI - Factors influencing waiting lists and cost of surgical treatment. PMID- 1863060 TI - The surgical value of community hospitals: a closer look. AB - To assess and compare the safety and efficiency of a surgical unit at a District General Hospital and a Community Hospital for elective cold surgery. A retrospective survey was made using regional computer Hospital Activity Analysis data and monthly audit meeting records of all inpatients having selected elective general surgical operations on one consultant's firm over a period of one year, at Torbay Hospital, Torquay, (DGH) and Newton Abbot Hospital, Newton Abbot (CH). All inpatients and day cases admitted under CACC from April 1, 1987, until March 31, 1988, were studied comparing mortality, morbidity and efficiency for comparable elective surgical procedures. A postal questionnaire to assess patient satisfaction with surgical care at both hospitals was included in the study. 350 patients underwent elective surgical procedures at the DGH and 380 patients underwent similar procedures at the CH. There was no significant increase in mortality and morbidity at the CH, which was preferred by most patients for routine surgical operations. The Community Hospital unit was found to be satisfactory and more efficient for routine elective surgery as determined from the above parameters and the patients themselves. PMID- 1863061 TI - Nursing tackles tough issues in sweeping reform proposal. PMID- 1863063 TI - Pediatric preoperative tours. Successful hospital program expands to community. PMID- 1863062 TI - Liability for injury resulting from poor patient positioning. PMID- 1863064 TI - Gamete intrafallopian transfer. Another approach for the treatment of infertility. PMID- 1863065 TI - Cardiopulmonary bypass. Principles, nursing implications. AB - As techniques become more advanced, perioperative nurses in all surgical specialties must increase their knowledge to provide safe patient care. Cardiopulmonary bypass for cardiac surgery demands special knowledge and skills. Knowledge of the principles of CPB allows the nurse to give excellent nursing care and to function as an effective member of the health care team. PMID- 1863066 TI - Pancreatic duct calculi. Treatment by pulsed dye laser. AB - Endoscopic sphincterotomy with stone extraction has been successful in the majority of patients with biliary stones; however, large biliary stones and pancreatic stones in the smaller pancreatic duct may require a new approach. Pulsed dye laser has proven effective in treating pancreatic duct calculi during ERCP. With an outpatient procedure to eliminate pancreatic duct calculi, patients can be treated safely and effectively without major surgery. The procedure is less invasive for the patient, thereby reducing morbidity and expense. PMID- 1863067 TI - Splenic salvage vs splenectomy. Care of the trauma patient. AB - Because of the incidence of overwhelming postsplenectomy sepsis that occurs after splenectomy, there is an increased incentive to try to salvage the spleen in patients with splenic injury. Even though operative time is increased by this technique, the advantage of immunologic competence is well worth the added operative time. In hemodynamically unstable patients, however, splenectomy remains the method of choice. PMID- 1863068 TI - Surgical nurse liaison. Expediting the surgical admission process. PMID- 1863069 TI - A history of the RN first assistant reimbursement issue. PMID- 1863070 TI - The basics of bar code technology. PMID- 1863071 TI - Treatment of acanthosis nigricans with tretinoin. PMID- 1863072 TI - On a clear day you can see forever. PMID- 1863073 TI - Idiopathic and L-tryptophan-associated eosinophilic fasciitis before and after L tryptophan contamination. AB - Recently, a causative association has been made between the ingestion of levotryptophan (L-tryptophan) and the eosinophilia-myalgia syndrome (EMS), a new entity manifested by peripheral blood eosinophilia, myalgias, constitutional symptoms, and cutaneous edema with fibrosis. Contaminated levotryptophan preparations produced at a single manufacturing company between October 1988 and June 1989 have been implicated in all EMS cases. In this study, we analyzed retrospectively 49 patients with cutaneous fibrosis for a history of levotryptophan use. Levotryptophan ingestion prior to the onset of their disease was reported by 11 (65%) of 17 patients with eosinophilic fascilitis (EF), two (20%) of 10 patients with localized scleroderma, and none of 22 patients with systemic sclerosis. The onset of levotryptophan-associated cutaneous disease preceded the availability of contaminated levotryptophan preparations in seven (54%) of 13 patients. One patient with levotryptophan-associated generalized morphea also had lichen sclerosus et atrophicus and acanthosis nigricans, findings not previously reported in patients with EMS. In addition, we compared the clinical and laboratory features of levotryptophan-associated EF and idiopathic EF. Myalgias, muscle weakness, paresthesias, morpheaform plaques, cutaneous ulcers, and livedo reticularis were more common in patients with levotryptophan-associated EF. We conclude that levotryptophan-associated EF and localized scleroderma were present before the presumed date of contaminated levotryptophan availability. The clinical spectrum of cutaneous fibrosis associated with the ingestion of levotryptophan includes generalized morphea and EF, which are similar though not identical to their idiopathic counterparts. PMID- 1863074 TI - Transforming growth factor alpha expression helps to distinguish keratoacanthomas from squamous cell carcinomas. AB - Keratoacanthomas may be difficult to distinguish histologically from squamous cell carcinomas. We studied 20 keratocanthomas and 22 squamous cell carcinomas immunohistochemically using an antibody directed against transforming growth factor alpha to determine if the pattern of transforming growth factor alpha expression would provide a useful method of differentiating these tumors. Ninety percent of the keratoacanthomas demonstrated a diffuse pattern within tumor lobules in which all but the most peripheral rim of cells were stained. A similar localization of transforming growth factor alpha was not identified in squamous cell carcinomas. In addition, 40% of the squamous cell carcinomas but none of the keratoacanthomas showed focal transforming growth factor alpha immunostaining. Our results suggest that transforming growth factor alpha expression may be a marker of epithelial differentiation and may help distinguish between these two tumors. PMID- 1863075 TI - Prevalence and characteristics of anti-single-stranded DNA antibodies in localized scleroderma. Comparison with systemic lupus erythematosus. AB - Prevalence, levels, and immunoglobulin classes of anti-single-stranded DNA antibodies were determined by an enzyme-linked immunosorbent assay in 52 patients with localized scleroderma (33 with morphea, four with generalized morphea, and 15 with linear scleroderma), in 60 healthy controls, and, for comparison, in 31 patients with systemic lupus erythematosus. Localized scleroderma revealed a significant prevalence of anti-single-stranded DNA antibodies, mainly characterized by high levels and IgM and IgA isotypes. Comparison of antibody characteristics in different clinical forms of localized scleroderma showed some significant differences (levels and immunoglobulin isotypes). Comparison with systemic lupus erythematosus showed that frequency, high levels, and IgG isotype of anti-single-stranded DNA antibodies significantly prevailed in systemic lupus erythematosus, while the IgM isotype significantly prevailed in localized scleroderma. However, generalized morphea and linear scleroderma did not significantly differ from systemic lupus erythematosus as regards antibody frequency and prevalence of high antibody levels. PMID- 1863076 TI - Incidence of psoriasis in Rochester, Minn, 1980-1983. AB - This population-based study was carried out using the medical records linkage data resource for the population of Rochester, Minn, at Mayo Clinic. There were 132 newly diagnosed cases of psoriasis identified during a 4-year period (1980 through 1983); 88% of the cases had been seen and diagnosed by a dermatologist. The overall crude incidence rate was 57.6 per 100,000 population; for men and women, the rates were 54.4 and 60.2, respectively. The overall sex- and age adjusted (1980 US white population) incidence rate was 60.4 per 100,000 person years. The highest rate of occurrence (112.6) was in the 60- to 69-year-old age group. Most of the cases of psoriasis diagnosed in this study (58%) were mild, and the patients had psoriatic lesions on less than 10% of their body. There are no other published incidence rates for this condition with which to make comparisons. PMID- 1863077 TI - Invasive cutaneous melanoma in elderly patients. AB - Clinical and pathologic variables were compared between "older" (greater than or equal to 70 years) and "younger" (30 to 39 years) patients with primary invasive cutaneous melanoma. Older patients had more nodular melanomas and acral lentiginous melanomas (58%); superficial spreading melanomas predominated in younger patients (74%). Mean tumor thickness was greater in the older patients (3.95 vs 2.02 mm). Invasive levels 2 and 3 occurred more often in younger patients (41.1% vs 13%); level 5 occurred more often in older patients (30.4% vs 5.3%). Microscopic ulceration occurred more often in older (46.4%) than in younger patients (19.4%). Older patients classified as clinical stage I at presentation or with primary lesions 1.50- to 3.00-mm thick had poorer survival. Younger women survived longer than younger men; this was not true of older patients. The elderly patients with cutaneous melanoma were more likely to have poor prognostic features and thus more likely to die from melanoma than the younger patients. PMID- 1863078 TI - Nonmelanoma skin cancer mortality. A population-based study. AB - To estimate the magnitude of nonmelanoma skin cancer mortality and describe its parameters, we reviewed the medical records of all deaths certified as due to this cause among Rhode Island residents from 1979 through 1987. After excluding acquired immunodeficiency syndrome-associated Kaposi's sarcoma, we confirmed that nonmelanoma skin cancer was the cause of death for 51 individuals, a quarter of the number of melanoma deaths reported. The age-adjusted nonmelanoma skin cancer mortality rate was 0.44/10(5) per year. Fifty-nine percent were due to squamous cell carcinoma, and 20% were due to basal cell carcinoma. Most appeared actinically induced. Among deaths from squamous cell carcinoma, the mean age was 73 years. At least 80% of the squamous cell carcinomas metastasized, and 47% arose on the ear. None appeared due to refusal of treatment. Among deaths from basal cell carcinoma, the mean age was 85 years, and refusal of surgical intervention was documented in 40%. Study of nonmelanoma skin cancer mortality provides for estimation of the magnitude of this problem, complements other studies of prognosis, and helps guide prevention, early detection, and treatment. PMID- 1863079 TI - Isolation of human immunodeficiency virus type 1 in cutaneous blister fluid. AB - The human immunodeficiency virus type 1 (HIV-1) has been isolated from a number of body fluids, including semen, tears, cerebrospinal fluid, saliva, breast milk, alveolar fluid, and vaginal fluid, but it has not been isolated from fluid containing skin lesions. We report the isolation of HIV-1 from cutaneous blister fluid in a patient with concomitant HIV-1 infection and porphyria cutanea tarda. Although transmission of HIV-1 through casual contact has not been reported, appropriate precautions should be taken to avoid direct contact with cutaneous fluid-containing lesions in HIV-1-positive patients. PMID- 1863080 TI - Costal fringe. AB - Costal fringe consists of a bandlike pattern of venous telangiectases along the anterolateral costal margins. It is a common and easily recognized entity, usually seen in elderly men. Association with underlying disease is not well established. To assess the frequency of costal fringe in a healthy young adult population, we examined 1523 active duty Air Force personnel (1203 men and 320 women) between the ages of 17 and 34 years. All subjects were human immunodeficiency virus seronegative; none had known hyperestrogenic or other disease states. Costal fringe was present in only three individuals, all men, a frequency of 0.2%. Costal fringe is a rare finding in healthy young adults. PMID- 1863081 TI - Medical defense against blistering chemical warfare agents. AB - First used in World War I, chemical blistering agents present a serious medical threat that has stimulated renewed interest in the light of extensive use in recent conflicts. Current medical management cannot yet prevent or minimize injury from the principal agent of concern--sulfur mustard. Research directed at this goal depends on defining effective intervention in the metabolic alterations induced by exposure to sulfur mustard. PMID- 1863082 TI - Unraveling the eosinophilia-myalgia syndrome. PMID- 1863083 TI - Recurrent erythematous nodule on the sole of the foot. Recurrent pyogenic granuloma. PMID- 1863084 TI - Scaly atrophic lesions both scattered and in linear arrays. Disseminated superficial actinic porokeratosis in a patient with linear porokeratosis. PMID- 1863085 TI - Puzzling palmar and plantar papules. Porokeratotic eccrine ostial and dermal duct nevus. PMID- 1863086 TI - Pigmented lesions in a patient with pulmonary tuberculosis. Pityriasis rotunda. PMID- 1863087 TI - Unusual skin tumors in Langerhans cell histiocytes. PMID- 1863088 TI - Quantification of the extent and the severity of atopic dermatitis: the ADASI score. PMID- 1863089 TI - No evidence of hearing loss in patients with vitiligo. PMID- 1863090 TI - Fatal melanoma arising in a zosteriform speckled lentiginous nevus. PMID- 1863091 TI - Lipid peroxides and superoxide dismutase activity in trichophyte lesions. PMID- 1863092 TI - Cleft lip--is there light at the end of the tunnel? PMID- 1863093 TI - Adrenoleucodystrophy. PMID- 1863094 TI - The reliability of height and height velocity in the assessment of growth (the Wessex Growth Study) AB - Both biochemical and auxological measurements can be used to assess growth. Quality control in routinely reported in laboratory studies, but the reproducibility of height measurements, and the height velocity data derived from them, is seldom considered. We have previously established our error and in this report we examine its implications for the screening of short children and subsequent monitoring of their growth. The 95% confidence interval for height for a 5 year old observed to be on the 3rd centile for height, spanned the 2nd-4th centile. However, the confidence interval for a 12 month height velocity appropriate to such a child spanned the 8th-52nd centiles, the lower limit pathological and the upper more than satisfactory. A single height velocity even over 12 months therefore lacks the precision to provide a reliable index of current growth in short children. Furthermore, serial height velocity calculations on a cohort of 78 short normal children showed no significant correlation from year to year, suggesting that velocity is also unable to predict future growth. Although the proportion of this cohort of short children lying beneath the 25th centile for velocity remained constant from year to year, the identity of the individuals comprising that proportion changed, a phenomenon which could be largely accounted for by the random error associated with height velocity. Our data suggest that, by the time a trend in abnormal velocity is reliably established, a deviation from the height centiles is clearly evident. Although velocity charts are attractive in concept, they seem to be no more discriminating than height charts in practice, and may be clinically deceptive unless interpreted with great care. PMID- 1863095 TI - Growth prognosis and growth after menarche in primary hypothyroidism. AB - The long term growth of 20 girls and nine boys with juvenile primary hypothyroidism was studied until they reached final height. At diagnosis the girls had a mean age of 8.8 years (range 3.0-13.0); mean bone age was 5.4 years. The mean age of the boys at diagnosis was 9.5 years (range 3.7-14.2); mean bone age was 6.3 years. The patients were treated with thyroxine 100 micrograms/m2/day and serum thyroxine concentrations were maintained in the normal range. During treatment the rate of skeletal maturation exceeded the change in chronological age. Initial mean height SD score for bone age before treatment in the girls was +0.59 and after 11 years of treatment fell to -0.55 Mean height SD score for bone age in the boys decreased from +1.6 to -0.87 during treatment. In the girls the onset of puberty was 1.2 years later than the normal population but the duration of puberty was reduced. Mean age (SD) of menarche was 13.8 (1.7) years. The pattern of growth in girls with treated hypothyroidism was abnormal as growth continued after menarche, at a time when normal girls have almost stopped growing. During the second year after menarche our patients still had a mean growth velocity of 4.1 cm/year. Our data suggest that juvenile primary hypothyroidism results in a permanent height deficit. In addition, there is a loss of the normal harmony between growth and sexual maturation in girls, despite adequate treatment, in that growth continues for much longer after menarche than in normal girls. PMID- 1863096 TI - Treatment of constitutional growth delay in prepubertal boys with a prolonged course of low dose oxandrolone. AB - Forty six prepubertal boys who had constitutional growth delay were treated with oxandrolone. Mean age at the onset of treatment was 11.9 years (range 9.0-14.0) and bone age delay was 1.9 'years'. The dose of oxandrolone used was a mean of 0.05 mg/kg (range 0.03-0.18) for a mean of 0.9 years (range 0.2-3.6). Height velocity increased from a mean (SD) before treatment of 4.0 (1.0) to 7.5 (1.2) cm/year with oxandrolone. Growth rate was sustained at 7.6 (2.2) cm/year in the period after treatment. Those boys who attained a testicular volume of 4 ml or greater at the end of the treatment period had the most pronounced sustained growth acceleration. Height for bone age SD score did not alter significantly from a mean of -1.0 before treatment to -1.2 after treatment. Oxandrolone is a safe and effective treatment for prepubertal boys with constitutional growth delay. PMID- 1863097 TI - Screening for familial hypercholesterolaemia by measurement of apolipoproteins in capillary blood. AB - A total of 3025 families with schoolchildren aged 6-8 years were offered pilot screening for familial hypercholesterolaemia by measurement of the concentrations of apolipoproteins A-1 and B in the children's capillary blood and by analysis of their family histories of early ischaemic heart disease. The concentrations of the apolipoproteins were determined by double rocket immunoelectrophoresis of an eluate of blood spotted on filter paper. Results were available from 2085 children. Because their B:A-1 ratio was above the 97.5 centile and their concentration of B was above the 99th centile, 54 children (2.6%) were selected to have their apolipoprotein concentrations reassessed. The 17 children (0.8%) whose values were persistently above the chosen cut off points, and all of their available first and second degree relatives, had fasting determinations of serum lipid concentrations carried out. Raised serum concentrations of low density lipoprotein cholesterol and an autosomal dominant pattern of hypercholesterolaemia were found in 12 children and 10 families, respectively, suggesting a higher incidence of familial hypercholesterolaemia than the reported 1:500. Further investigations among family members disclosed hypercholesterolaemia in 29 relatives. A family history of early ischaemic heart disease was elicited by questionnaire, and was positive in only five of the 12 schoolchildren with hypercholesterolaemia. We conclude that analysis of apolipoproteins from capillary blood spotted on filter paper is suitable for screening for familial hypercholesterolaemia, and that this method is more efficient than screening based on family history. PMID- 1863098 TI - Gastro-oesophageal reflux and respiratory function in infants with respiratory symptoms. AB - This study aimed to define the incidence and severity of gastro-oesophageal reflux (GOR), as measured using 24 hour oesophageal pH monitoring, in 38 infants with recurrent respiratory symptoms and to relate these findings to measures of respiratory function. Twenty one infants had a pH under 4 for more than 5% of the time (one definition of abnormal GOR) and nine had GOR exceeding age related normal values. Maximum expiratory flow at functional residual capacity was reduced in 37 infants, airways resistance was raised in 19 infants, and thoracic gas volume was abnormal in 11 infants. There was no association between indices of GOR and measures of lung function whether assessed by correlation or by chi 2 analysis for normal versus abnormal values. However, individual infants appeared to have respiratory symptoms produced by GOR. This suggests that host responsiveness to GOR may be of greater relevance than the amount of GOR. PMID- 1863099 TI - Vaccine efficacy and control measures in pertussis. AB - An outbreak of pertussis in primary school-children in the St David's area of Pembrokeshire provided the opportunity to estimate pertussis vaccine efficacy. The estimate of efficacy was 88% when notified cases were used, but this fell to 68% when all children with bouts of coughing for two or more weeks were included. Notified cases were significantly less likely to have been vaccinated than other cases with similar symptoms. Therefore vaccine efficacy estimates based upon notified cases are likely to be biased. However, even the lower estimates suggest that pertussis immunisation is highly desirable and efforts to improve coverage should be increased. PMID- 1863100 TI - Acquired aplastic anaemia: still a serious disease. AB - Over 15 years, 42 children aged 2-14 years were diagnosed as having acquired aplastic anaemia. Adequate clinical details were available for 38 children who were categorised as very severe (n = 13), severe (n = 16), or nonsevere (n = 9) by the modified Camitta criteria. Treatment varied over the study period. Seven children received a bone marrow allograft from a full match family donor and three a matched unrelated donor transplant after failed treatment with antilymphocyte globulin. The remainder were treated with antilymphocyte globulin (n = 11), antilymphocyte globulin and oxymetholone (n = 4), oxymetholone with or without prednisolone (n = 12), or supportive treatment alone (n = 1). With a minimum follow up of one year since treatment, the five year survival was 70% for bone marrow transplantation with a family donor, 30% for antilymphocyte globulin, and 25% for oxymetholone. All three children with a matched unrelated donor transplant died. The prognosis of acquired aplastic anaemia remains poor for most children and new approaches to treatment are urgently required. PMID- 1863101 TI - Referrals to child psychiatry--a survey of staff attitudes. AB - A questionnaire study was conducted in a health district to evaluate the attitudes of paediatricians and child psychiatry staff as to which categories of problems should be referred to child psychiatry. In the majority of categories the two groups disagreed as to the frequency with which the problem should be referred. In the categories relating to child sexual abuse responses were often not in accord with Department of Health and Social Security guidelines. Reasons for not referring were also looked at and again it was found that there were a number of significant differences in opinion as to what are reasons for not referring to child psychiatry. Both groups agree that lack of communication is a reason for non-referral. Some suggestions are made as to how this problem could be addressed. PMID- 1863102 TI - Children with pervasive refusal. AB - Four children are described with a potentially life threatening condition manifested by profound and pervasive refusal to eat, drink, walk, talk, or care for themselves in any way over a period of several months. The multiplicity and severity of the symptoms in these children do not fit comfortably into any existing diagnostic category. Long term and highly skilled nursing and psychiatric care is required to help these children to recover. The possible causes of this syndrome are discussed. PMID- 1863103 TI - Intestinal permeability after single dose gluten challenge in coeliac disease. AB - The changes of intestinal permeability before and after a gluten load were studied. The study group comprised 27 patients with coeliac disease (mean age 12.3 years) and 19 healthy controls matched by sex and age. Intestinal permeability was studied by measuring the urinary excretion of two sugars, lactulose and L-rhamnose, before and six hours after the ingestion of five palatable biscuits made with 50 g of gluten powder. The patients with coeliac disease had been on a gluten free diet during the previous two years. After the gluten load lactulose and L-rhamnose urinary excretion changed significantly in patients, and a significant increase in the lactulose: L-rhamnose ratio was also observed. No significant changes were observed in the controls. In view of the modification of the three biopsies diagnostic protocol made by the European Society for Paediatric Gastroenterology and Nutrition, permeability tests associated with single gluten challenges may be an added contribution to the accuracy of the diagnosis in childhood. PMID- 1863104 TI - Alteration of urinary carnitine profile induced by benzoate administration. AB - To study the effect of sodium benzoate on carnitine metabolism, the acylcarnitine profile in the urine of five normal volunteers and two patients with urea cycle disorders was examined with fast atom bombardment-mass spectrometry. The volunteer subjects were given 5 g of sodium benzoate orally and the two patients with urea cycle disorders (carbamyl phosphate synthetase deficiency type I and ornithine transcarbamylase deficiency) were already undergoing treatment with sodium benzoate and L-carnitine. The amount of benzoylcarnitine excretion depended on the dose of both sodium benzoate and L-carnitine in a reciprocal relation. Increased excretions of acetylcarnitine and propionylcarnitine were also noted after sodium benzoate administration. The alteration of the urinary aclycarnitine profile was consistent with the change of mitochondrial CoA profile predicted by in vitro studies of an animal model. It is suggested that urinary acylcarnitine analysis is important to assess the effect of benzoate administration on mitochondrial function in vivo. Supplementation with carnitine may be necessary to minimise the adverse effects of sodium benzoate treatment in hyperammonaemia. PMID- 1863105 TI - Subcutaneous or intramuscular insulin injections. AB - To find out whether diabetic children may inject their insulin intramuscularly rather than subcutaneously, a random sample of 32 patients aged 4.3-17.9 (median 11.3) years was studied. Distance from skin to muscle fascia was measured by ultrasonography at standard injection sites on the outer arm, anterior and lateral thigh, abdomen, buttock, and calf. Distances were greater in girls (n = 15) than in boys (n = 17). Whereas in most boys the distances were less than the length of the needle (12.5 mm) at all sites except the buttock, in most girls, the distances were greater than 12.5 mm except over the calf. Over the fascial plane just lateral to the rectus muscle the distance from skin to peritoneum was less than 12.5 mm in 14 of the 17 boys and one of the 15 girls. Twenty five of the 32 children injected at an angle of 90 degrees, and 24 children raised a skinfold before injecting. By raising a skinfold over the anterior thigh, the distance from skin to muscle fascia was increased by 19% (range 0-38%). We conclude that most boys and some girls who use the perpendicular injection technique may often inject insulin into muscle, and perhaps on occasions into the peritoneal cavity. PMID- 1863106 TI - Scalp tumours mimicking encephaloceles. AB - Two neonates presented with benign scalp tumours that mimicked encephaloceles. In the more recent case ultrasonography confirmed that the tumour was extracranial. PMID- 1863107 TI - Epidemiology of hypochromic anaemia in young children. PMID- 1863108 TI - Accidents to children: the doctor's role. Education or environmental change? PMID- 1863109 TI - Paediatric care in general practice. PMID- 1863110 TI - Use of movement analysis in understanding abnormalities of gait in cerebral palsy. PMID- 1863111 TI - Recurrent abdominal pain of gastrointestinal disorder. PMID- 1863112 TI - When does slow weight gain become 'failure to thrive'? PMID- 1863113 TI - Baby Check score card. PMID- 1863114 TI - Ischaemic brain lesions diagnosed at birth in preterm infants. PMID- 1863115 TI - Neonatal infections with coagulase negative staphylococci. PMID- 1863116 TI - Endotoxin induced cochlear damage. PMID- 1863117 TI - Head injury--how community paediatricians can help. PMID- 1863118 TI - Photic sneezing. PMID- 1863119 TI - Duplicate publications. PMID- 1863120 TI - Cost implications of different approaches to the prevention of respiratory distress syndrome. AB - Because the incidence of both neonatal respiratory distress syndrome and neonatal mortality can be reduced by giving corticosteroids to women expected to deliver preterm and by giving surfactant to babies at high risk of developing hyaline membrane disease, we have considered what effects the adoption of one or both of these preventive policies would have on the costs of neonatal care. We have estimated the effects of treatment from overviews of the relevant controlled trials, and estimated costs from observations of care at one neonatal unit. Our results suggest that if either of these policies is adopted for all babies under 35 weeks' gestation at a drug cost of 150 pounds or less/baby, the overall costs of care would be reduced by between 1 and 10%. The cost per survivor would be reduced by up to 16% even if the drug cost were to be as high as pounds 550/baby. If the policies were to be adopted only for babies under 31 weeks' gestation, both policies would result in a reduction in cost of between 5 and 16%/survivor, although the increased survival resulting from the policies would lead to an increase in overall costs for babies of less then 31 weeks' gestation of between 7 and 32%. PMID- 1863121 TI - Multicentre randomised controlled trial of high against low frequency positive pressure ventilation. Oxford Region Controlled Trial of Artificial Ventilation OCTAVE Study Group. AB - A total of 346 infants aged less than 72 hours were randomly allocated to be treated either by high frequency positive pressure ventilation (HFPPV; rate fixed at 60/minute throughout treatment and initial inspiratory:expiratory (I:E) ratio 1:2, increased to 1:1 if necessary) or by low frequency positive pressure ventilation (LFPPV; rate less than or equal to 40/minute and initial I:E ratio usually 1:1, both decreasing during weaning). The main hypotheses were that HFPPV reduces pneumothorax, chronic lung disease and death before discharge in all infants, as well as those with hyaline membrane disease, and that it reduces the incidence of later neurodevelopmental complications in infants of less than 33 weeks' gestation. Among all the infants the rate of pneumothorax was 19% in the HFPPV group and 26% in the LFPPV group (p = 0.13; odds ratio 0.7, 95% confidence intervals (CI) 0.4 to 1.1); there was no difference in mortality or the incidence of chronic lung disease. In infants of less than 33 weeks' gestation there were no differences in adverse neurodevelopmental outcomes. Among the subgroup of 237 infants with hyaline membrane disease, median fractional inspired oxygen at the time of entry to the trial was 0.6 in the HFPPV group and 0.7 in the LFPPV group, indicating that many had moderately severe disease. In patients with hyaline membrane disease HFPPV was associated with a lower rate of pneumothorax (18% in the HFPPV group compared with 33% in the LFPPV group, p = 0.013, odds ratio 0.5, 95% CI 0.3 to 0.8, with no differences in mortality, or in duration of intubation or supplementary oxygen in survivors. As used in this study, HFPPV was the preferred ventilator regimen for infants with hyaline membrane disease. PMID- 1863122 TI - Factors associated with chronic lung disease in preterm infants. AB - Among 659 infants of 30 weeks' gestation or less born in a regional perinatal centre between 1983 and 1989, 195 were ventilated for four days or more and survived to 28 days, and 87 of these developed chronic lung disease. There was a sevenfold increase in the annual incidence of chronic lung disease over time. During the same period there were significant increases in the number of infants who survived, the incidence of septicaemia, and the use of parenteral lipid emulsions. Chronic lung disease was significantly associated with low birth weight, shorter gestation, duration of ventilation, vaginal delivery, sepsis, and the use of lipid. Respiratory and physiological measurements at 96 hours were significantly worse in infants who subsequently developed chronic lung disease. Initial logistic regression showed that gestation, arterial carbon dioxide tension (PaCO2), and ventilation rate at 96 hours; and birth in 1988 or 1989, were independently associated with chronic lung disease, but when septicaemia and use of lipid during the first 21 days were included, only gestational age (odds ratio 0.64, 95% confidence interval (CI), 0.49 to 0.81 for each week) and use of lipid (odds ratio 8.1, 95% CI, 2.32 to 28.0) remained significantly associated with chronic lung disease. The observed increase in incidence of chronic lung disease in this population was associated with earlier use of parenteral lipids in infants of very low gestation rather than with changes in population, survival, or ventilator treatment of respiratory distress syndrome. PMID- 1863123 TI - Phosphorus metabolites in the human placenta estimated in vivo by magnetic resonance spectroscopy. AB - Normal human placental metabolism has been studied in vivo by image localised 31P magnetic resonance spectroscopy in 13 women with anterior placentas; five, however, were too fat for useful spectral signals to be obtained. Magnetic resonance spectra of good quality which were considered to have arisen from the placenta were obtained from seven women with uncomplicated pregnancies (median gestational age 35 weeks, range 28-39). One other woman had a twin pregnancy in which one fetus had died a few days before. The phosphodiester signal from the placenta of the dead fetus was outside the 95% confidence intervals for normal placentas, suggesting that this technique may potentially be useful in the assessment of placental function. PMID- 1863124 TI - Temperature instability during nursing procedures in preterm neonates. AB - The temperature changes associated with total care nursing procedures were studied on 249 occasions during the first week of life in 25 preterm infants weighing less than 1500 g, 16 of whom weighed less than 1100 g. Large drops in both central and peripheral temperature occurred, with widening of the central peripheral temperature gap. Recovery of the temperature after the total care procedure took up to two hours. These routine nursing procedures are carried out every four to six hours. They cause an important alteration in the environmental temperature with consequent thermal stress to the infants that may influence ultimate outcome. PMID- 1863125 TI - Site of upper airway obstruction in preterm infants with problematical apnoea. AB - Airway obstruction is an important factor predisposing to the development of apnoea in preterm infants. An ultrafine fibreoptic scope was used to examine the upper airway of 12 preterm infants with recurrent problematical apnoea. Continuous visualisation of the airway was possible and recorded on to videotape together with simultaneous cardiorespiratory monitoring to detect apnoeic episodes in 12 infants studied. In seven infants obstruction was observed at laryngeal level with the arytenoid masses and aryepiglottic folds closing across the vocal cords. This was not only observed in obstructive apnoea but also during mixed apnoea in periods where no respiratory effort was detectable and again in apparently pure central apnoea. The findings confirm the larynx as an anatomical site of upper airway obstruction. They agree with other indirect methods of assessing airway patency that obstruction has an important role in the pathophysiology of apnoea of prematurity. PMID- 1863126 TI - Effect of intervention on development of hip posture in very preterm babies. AB - Preterm babies are physiologically hypotonic, which causes their posture to be flattened when lying in the prone position. This flattened posture may persist beyond term. In a prospective, randomised, controlled, double blind trial of postural support carried out on 45 babies born at less than 33 weeks of gestation, we showed that infants positioned with specific hip support during the period of intensive care had significantly fewer features of flattened posture at the age equivalent to term. PMID- 1863127 TI - Doppler assessment of pulmonary artery pressure during recovery from hyaline membrane disease. AB - The changes in pulmonary artery pressure during recovery from hyaline membrane disease were studied by serial Doppler echocardiography on 37 preterm infants. Pulmonary artery pressure was assessed noninvasively by its inverse relationship with the ratio of pulmonary artery Doppler time to peak velocity and right ventricular ejection time. The pattern of rise in ratio after the acute phase of hyaline membrane disease divided into three types. In 25 infants the ratio returned to the normal range: in 12 (group 1) at the same time as the fractional inspired oxygen fell below 0.5 and in 13 (group 2) after a delay of at least 24 hours. In 12 infants (group 3) the ratio remained below the normal range during their hospital stay, suggesting pulmonary artery pressure remained high. Infants in group 3 were of significantly lower gestation and required oxygen treatment for significantly longer than infants in groups 1 and 2. Persistently raised pulmonary pressures in group 3 may reflect lung damage either directly affecting pulmonary vasculature or exerting a secondary effect on pulmonary vascular resistance through hypoxaemia. PMID- 1863128 TI - Absent or reversed end diastolic flow velocity in the umbilical artery and necrotising enterocolitis. AB - Absent or reversed end diastolic flow (AREDF) velocities in the umbilical artery were identified in 25 high risk pregnancies. In six pregnancies the fetus was abnormal and all but one of these ended in perinatal death. Of the 19 morphologically normal fetuses, three died in utero and there were four neonatal or infant deaths. The mortality rate was 48% for all pregnancies and 37% for those with morphologically normal fetuses. There was a highly significant increased risk for the development of necrotising enterocolitis in these morphologically normal fetuses with AREDF (53%) compared with controls (6%) who did have umbilical artery end diastolic flow velocities in fetal life. There were no significant differences between the matched pairs for parameters of neonatal outcome chosen to reflect neonatal morbidity. These findings demonstrate the close association between AREDF and necrotising enterocolitis that appears to be independent of other variables such as degree of growth retardation, prematurity, and perinatal asphyxia. PMID- 1863129 TI - Fibrinolysis in cerebrospinal fluid after intraventricular haemorrhage. AB - Concentrations of cross linked fibrin degradation products were measured in the cerebrospinal fluid from five 'normal' preterm infants (median 102 ng/ml), four preterm infants with intraventricular haemorrhage (median 315 ng/ml), and five infants with progressive post-haemorrhagic ventricular dilatation (median 1000 ng/ml). Serial samples of cerebrospinal fluid from one infant showed a peak concentration two weeks after the haemorrhage. PMID- 1863130 TI - Erythropoietin responsive progenitors in anaemia of prematurity. AB - Circulating erythroid progenitors (BFU-E) in five anaemic preterm infants (haemoglobin less than 100 g/l) were about 2 and 4.4 times as abundant as in 10 preterm infants who were not anaemic and five healthy adults, respectively, and were significantly more responsive to low concentrations of recombinant human erythropoietin (rHuEpo) than those from healthy adults. These results encourage further studies in the use of rHuEpo for the treatment of the anaemia of prematurity. PMID- 1863131 TI - Preterm prelabour rupture of membranes. PMID- 1863132 TI - Antenatal diagnosis of inborn errors of metabolism. PMID- 1863133 TI - Computerised neonatal information systems. PMID- 1863134 TI - Graduate education in thoracic surgery. PMID- 1863135 TI - Pulmonary metastases revisited. PMID- 1863136 TI - Bio-medicus ventricular assistance. PMID- 1863137 TI - Effects of internal mammary artery dissection on phrenic nerve perfusion and function. AB - The effects of left internal mammary artery (LIMA) dissection and distal division on phrenic nerve perfusion and function were examined in an adult swine model. Phrenic nerve perfusion was determined by left atrial injection of radioactively labeled microspheres. Phrenic nerve function was determined by measuring nerve and diaphragm potentials evoked by bilateral phrenic nerve stimulation. In the first group of animals (n = 9), the LIMA was dissected with ligation of all its branches. Left phrenic nerve perfusion and function decreased after LIMA dissection in every animal studied, whereas only minimal changes were observed on the right. Sixty minutes after LIMA dissection, left phrenic nerve mean perfusion decreased 71%. Left phrenic nerve and left diaphragm mean action potential amplitudes decreased 54% and 80%, respectively. In the second group of animals (n = 4), the LIMA dissection was performed without division of the pericardiacophrenic artery, a small proximal branch of the internal mammary artery that supplies the phrenic nerve. Sixty minutes after LIMA dissection, left phrenic nerve perfusion had decreased by 21% from control values, with a corresponding decrease in left phrenic nerve and diaphragm mean action potential amplitudes of 19% and 23%, respectively. These results indicate that LIMA dissection with division of all its branches in this model is associated with a significant impairment in left phrenic nerve perfusion and function and suggests a causal relationship. These results may also explain the apparent increased phrenic nerve cold sensitivity and increased incidence of phrenic nerve dysfunction associated with LIMA grafting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863138 TI - Total cavopulmonary anastomosis versus conventional modified Fontan procedure. AB - The total cavopulmonary anastomosis, lateral tunnel Fontan, has been advocated as a preferred method for Fontan type repair. From 1987 to July 1990, 39 patients underwent total cavopulmonary anastomoses (group 1) and 39 patients underwent modified Fontan procedures (group 2); patients receiving adjustable atrial septal defects were excluded. Diagnoses in group 1 included tricuspid atresia in 5 patients, single ventricle in 32, and pulmonary atresia and intact ventricular septum in 2. Diagnoses in group 2 included tricuspid atresia in 20, single ventricle in 17, hypoplastic left heart syndrome in 1, and pulmonary atresia and intact ventricular septum in 1. There were no significant differences in age, weight, cross-clamp time, duration of inotropic support, postoperative effusions, or hospital stay between the two groups. Early mortality in group 1 was 7.7% (3/39) and in group 2, 2.6% (1/39). There was no difference in the incidence of early dysrhythmias or early pacemaker placement. Late mortality was 2.8% in group 1 and 8% in group 2 with a mean follow-up of 18 and 25 months, respectively. Follow-up in group 1 revealed 33 patients in normal sinus rhythm and 1 patient with episodes of supraventricular tachycardia; no additional patients have required pacemakers. Follow-up in group 2 revealed 27 patients in normal sinus rhythm and supraventricular tachycardia in 4 patients; 5 additional patients have required pacemaker placement. There is no apparent difference in early outcome between the total cavopulmonary anastomosis and the conventional modified Fontan. However, there appears to be an increased incidence of late dysrhythmias and the need for pacemaker placement in the conventional modified Fontan group compared with the lateral tunnel group. PMID- 1863139 TI - Reoperative pulmonary resection in patients with metastatic soft tissue sarcoma. AB - Resection of pulmonary metastases from soft tissue sarcoma has been shown to be associated with a 3-year survival of 25% to 30%. The role of multiple resections for recurrent pulmonary metastases, however, has not been clearly defined. Since 1976, 43 patients have had two or more thoracic explorations for the purpose of resecting pulmonary metastases from adult soft tissue sarcoma at our institution. In 89 reexplorations, through either median sternotomy or lateral thoracotomy, the operative mortality was 0%, and 31 of the 43 patients (72%) could be rendered free of disease at the second thoracotomy. Median survival from the second thoracotomy for the patients with resectable disease was 25 months, whereas median survival of patients who had unresectable disease was 10 months. A disease free interval between the first and second thoracotomies of greater than 18 months was associated with prolonged survival from the second thoracotomy. Owing to lack of other therapies with proven salvage efficacy and in the absence of randomized trials, repeated thoracotomies to render patients free of disease from pulmonary soft-tissue sarcoma metastases appear justified considering the potential survival benefit and low attendant risk. PMID- 1863140 TI - Improved survival after resection of pulmonary metastases from malignant melanoma. AB - The value of resecting pulmonary metastases from malignant melanoma was retrospectively examined. Between 1981 and 1989, 56 patients (35 men and 21 women with a mean age of 49 years) had 65 pulmonary resections for histologically proven metastatic melanoma after treatment of the primary tumor. In patients undergoing thoracotomy, 50% (28/56) had pulmonary metastases as the initial site of recurrence. Twenty-eight patients (50%) had local-regional recurrence before the development of lung metastases. Eight lobectomies, two segmentectomies, and 55 wedge excisions were done. Fifty-four patients (54/56, 96%) underwent complete resection, and there were no operative deaths. The postthoracotomy actuarial survival was 25% at 5 years (median interval, 18 months). Location of the primary tumor, histology, thickness, Clark level, local-regional lymph node metastases, or type of resection was not associated with improved survival. Patients without regional nodal metastases before thoracotomy had a median survival of 30 months compared with 16 months for all others (p = 0.04). Patients with lung as the site of first recurrence had a median survival of 30 months compared with 17 months for patients with initial local-regional recurrence (p = 0.038, log-rank test). Despite systemic spread, patients with isolated pulmonary metastases from melanoma may benefit from metastasectomy. PMID- 1863141 TI - Cardiac transplantation with corticosteroid-free immunosuppression: long-term results. AB - To assess the long-term safety of an immunosuppressive regimen without corticosteroids, we retrospectively evaluated 42 long-term (greater than 1 year) survivors of orthotopic cardiac transplantation. We determined the incidence of (1) conversion of the immunosuppressive regimen from cyclosporine and azathioprine alone (group I) to cyclosporine, azathioprine, and prednisone (group II), (2) late acute graft rejection (defined as occurring at greater than 1 postoperative year), and (3) major postoperative complications related to corticosteroids. Of the 42 patients who were started on cyclosporine and azathioprine, 48% remained in group I, and 52% converted to group II. Forty-five percent of group II patients were able to taper and discontinue prednisone in 15.6 +/- 2.2 months. Among the patients on long-term corticosteroid-free immunosuppression, the incidence of late rejection was 2.1% per endomyocardial biopsy. The incidence of late infectious episodes was not significantly different between the two groups of patients, although diabetes mellitus and hypercholesterolemia were more prevalent in group II than in group I. These data suggest that cardiac transplant recipients who chronically remain on corticosteroid-free immunosuppression represent a select group of patients with an acceptably low risk of late graft rejection and associated reduction of potential risk factors of accelerated coronary artery disease. PMID- 1863142 TI - Current indications, risks, and outcome after pericardiectomy. AB - A retrospective analysis of the records of 60 patients who underwent pericardiectomy over a 10-year period (1980 to 1990) at The Johns Hopkins Hospital was performed. Indications for operation were effusive disease in 24 patients and constriction in 36 patients. Six patients (10%) with pericardial effusion had pain as the primary symptom necessitating intervention. The operative approach for pericardiectomy was median sternotomy in 52 patients (4 patients required cardiopulmonary bypass) and left anterior thoracotomy in 8 patients. Nine patients (5 with constriction and 4 with effusion) with a prior limited pericardial procedure required formal pericardiectomy. The operative mortality rate for pericardial effusion and constriction was 4.2% and 5.6%, respectively. Follow-up (median follow-up, 56.9 +/- 38.2 months) was obtained on 56 patients (93.3%). Actuarial survival at 1 year, 5 years, and 10 years for all patients was 82.1% +/- 5.1%, 71.7% +/- 6.7%, and 59.8% +/- 12.2%, respectively. A Cox proportional hazards regression analysis was performed using 20 clinical variables. A history of malignancy, previous pericardial procedure, and preoperative New York Heart Association class IV were found to be predictors of poor survival. All patients who underwent operation primarily for effusion with associated pain are alive and have improved functional capacity without steroid use. We conclude that pericardiectomy can be performed with low mortality and can result in good long-term survival and improved functional capacity. Patients who are seen primarily with pain refractory to steroid therapy can be relieved of symptoms with operation. PMID- 1863143 TI - Internal mammary artery graft at reoperation: risks, benefits, and methods of preservation. AB - To determine the effect of a prior internal mammary artery (IMA) graft on coronary artery bypass reoperation (CABR), we reviewed our experience with 410 consecutive patients: 313 received only saphenous vein grafts at initial coronary artery bypass grafting (CABG), and 97 received at least one IMA graft at CABG. Cardiac catheterization data before CABG were available in 110 patients (56 received only saphenous vein grafts, 54 received at least one IMA graft), allowing comparison of left ventricular function at CABG and CABR. Injury of the IMA graft occurred in 5 patients (1 death), but presence of an IMA graft was not an independent predictor of morbidity or mortality. Overall, the incidences of complications and deaths were higher in patients with saphenous vein grafts than in patients with IMA grafts, though not significantly so. Internal mammary artery grafts better preserved cardiac function: patients with IMA grafts had worse left ventricular function before CABG but better left ventricular function before CABR than patients with saphenous vein grafts. Left ventricular function deterioration from before CABG to before CABR was significantly less in patients with IMA grafts. We conclude that the risk of CABR is not increased by a previously constructed IMA graft and that left ventricular function is better preserved at CABR when an IMA graft was constructed at the initial operation. PMID- 1863144 TI - Bio-medicus ventricular assist device for salvage of cardiac surgical patients. AB - Over a 5-year period, 41 (1%) of 4,193 patients undergoing cardiac operations underwent intraoperative or early postoperative insertion of a Bio-Medicus ventricular assist device when it became apparent that the patient could not otherwise survive. Fourteen patients were in cardiogenic shock and 7 were in cardiac arrest at the time of initiation of their primary cardiac surgical procedure, and in no instance was the device planned as a bridge to cardiac transplantation. Bleeding, sepsis, and thromboembolism were frequent postoperative complications. Central nervous system deficits were observed in 16 patients during their postoperative course. Eight patients (19.5%) were long-term survivors. Of the preoperative risk factors evaluated only age was significantly associated with survival, with 7 (33%) of the 21 younger (39 to 63 years) patients surviving. Blood product usage and hospital cost were analyzed in an attempt to assess cost/effectiveness of use of this device for attempted salvage of such desperately ill patients. PMID- 1863145 TI - Aortic valve replacement with omniscience and omnicarbon valves. AB - Clinical results achieved in 100 cases of aortic valve replacement with the Omniscience (O-S) valve during the period from 1980 to 1985 as well as 100 cases of aortic valve replacement with the Omnicarbon (O-C) valve during the period from 1985 to 1989 were studied. Concomitant surgical procedures including mitral valve replacement were performed in 63 patients in the O-S group and 67 patients in the O-C group. Cumulative follow-up in the two groups was carried out for a total of 559 and 273 patient-years, respectively. The overall 4-year actuarial survival rate was 82% +/- 3.8% in the O-S group and 89.5% +/- 3.2% in the O-C group, the corresponding rates for patients undergoing isolated aortic valve replacement being 82.9% +/- 4.2% in the O-S group and 91.9% +/- 3.5% in the O-C group. The overall 4-year actuarial event-free rate with respect to thromboembolic complications was 88.8% +/- 3.3% in the O-S group and 94.4% +/- 2.8% in the O-C group, as compared with the corresponding rates of 89.2% +/- 3.6% in the O-S group and 95.9% +/- 2.8% in the O-C group for patients undergoing isolated aortic valve replacement. The overall rate of valve-related complications, including thromboembolism, anticoagulant-related hemorrhage, perivalvular leak, infection, and structural failure, was 78.8% +/- 4.2% in the O S group and 89.3% +/- 3.5% in the O-C group (p less than 0.05), and for isolated aortic valve replacement, 79.7% +/- 4.5% in the O-S group and 89.6% +/- 4.1% in the O-C group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863146 TI - Preliminary results of left heart bypass in pigs using a heparin-coated centrifugal pump. AB - To assess the feasibility of left ventricular assist without systemic heparinization, we used a commercially available (Sarns 3M) centrifugal pump with tubing set and cannulas, all internally precoated for the purpose of this study with heparin, to bypass the left ventricle in 12 pigs for periods of either 1 or 3 hours. There was no significant activation of clotting and there was no sign of generalized embolization. However, on postmortem studies, 5 kidneys out of 22 examined showed signs of minimal thromboembolism. This experiment shows that artificial left ventricular assist, free of systemic heparinization but using heparin precoating, is feasible and safe, at least for a short period of time. PMID- 1863147 TI - Preoperative hemostatic activity and excessive bleeding after cardiopulmonary bypass. AB - The rationale for predicting the risk of excessive postoperative bleeding by assessing the hemostatic status of a patient before cardiopulmonary bypass was investigated. A novel, rapid, overall test (hemostatometry) consisting of a physiologically relevant test of platelet function (shear-induced hemostasis) and coagulation was performed using nonanticoagulated blood and compared with the routine coagulation screen. Two hundred five patients undergoing elective coronary revascularization were studied 3 to 4 days before operation. Forty-nine bled excessively for nonsurgical reasons; none were predicted by the routine coagulation tests. Using a stepwise discriminant analysis, hemostatometry correctly predicted 31 of 49 (63%). Thirty of 156 predicted as bleeders by hemostatometry did not bleed. Thus, preoperative hemostatometry predicted 77% of the true outcome. The false predictions suggest, however, that certain bleeding abnormalities probably acquired during cardiopulmonary bypass cannot be predicted. These findings do not justify the routine use of preoperative tests in assessing the bleeding risk in patients undergoing cardiopulmonary bypass. PMID- 1863148 TI - Current status of coronary artery operation in septuagenarians. AB - Previous reports of elderly patients undergoing coronary artery bypass grafting have not addressed the current era of aggressive percutaneous angioplasty and frequent urgent or emergent operation. To investigate this important subgroup of patients, we analyzed our recent coronary artery bypass grafting experience with patients 70 years of age or older. From January 1984 to January 1989, 121 consecutive patients in this age range underwent surgical revascularization at our institution. Overall in-hospital operative mortality (OM) was 7.4% (9/121), with 77.8% (7/9) of deaths due to cardiac causes. Serious postoperative morbidity occurred in 71.1% (86/121). Surgical priority was significantly correlated with operative mortality: for elective cases, the OM was 2.9% (2/68), but it was 8.6% (3/35) for urgent cases (p less than 0.05) and 22.2% (4/18) for emergency cases (p less than 0.05). Univariate analysis isolated the need for inotropic support, intraaortic balloon pump, reoperation, cardiopulmonary resuscitation, and emergency status as significant risk factors for OM (p less than 0.05). Multivariate stepwise logistic regression analysis identified the need for inotropic support, intravenous nitroglycerin, reoperative coronary artery bypass grafting, and hypertension as independently significant risk factors. A logistic risk equation developed from this population accurately modeled OM at the extremes of operative risk. Three (3.1%) of the 97 patients predicted to have less than 5% OM died, whereas all patients predicted by the model to have greater than 90% OM died. These results indicate that in spite of relatively high morbidity and mortality rates, elderly patients have a very acceptable operative risk in the current era of high-risk coronary artery bypass grafting. This is particularly true if elective revascularization is possible. PMID- 1863149 TI - Survival and valve failure after aortic valve replacement. AB - A prospective evaluation of 412 consecutive patients undergoing isolated aortic valve replacement between January 1982 and December 1985 was performed in an attempt to identify the determinants of survival and valve failure. A variety of valves were inserted to permit a prospective evaluation of alternative valves including: Bjork-Shiley mechanical (n = 37), Ionescu-Shiley pericardial (n = 261), Hancock pericardial (n = 78), and Carpentier-Edwards porcine (n = 36). Thirteen patients died in the hospital (3.2%) and 47 patients died in the follow up period producing an actuarial survival of 81% +/- 3% at 48 months. Survival was independently predicted by advancing age, preoperative New York Heart Association functional class, and the presence of endocarditis (p less than 0.05 by Cox regression analysis). The majority of patients were symptomatically improved (New York Heart Association class I or II: 21% preoperative, 88% postoperative). Freedom from structural valve dysfunction, prosthetic valve endocarditis, and reoperation for valve-related complications were 95% +/- 2%, 95% +/- 2%, and 92% +/- 2% at 48 months, respectively. These valve-related complications occurred more frequently in younger patients and in those with a Hancock pericardial valve (freedom from structural valve dysfunction, 89% +/- 5%; prosthetic valve endocarditis, 84% +/- 9%; reoperation, 78% +/- 10%; p less than 0.05 by Cox regression). Freedom from thromboembolism was 88% +/- 2% at 48 months; it was significantly lower in patients with a preoperative thromboembolic event and was not influenced by the type of prosthesis inserted. Freedom from anticoagulant-related hemorrhage was 85% +/- 8% at 48 months and was not influenced by any preoperative factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863150 TI - Regional myocardial stress distribution from magnetic resonance image-based mathematical models. AB - The instantaneous regional stress distribution within the myocardium, which cannot be directly measured, has been estimated using improved numerical methods and nonaxisymmetric biventricular geometry. To do this, we have employed computer aided solid mathematical modeling to generate a three-dimensional representation for an ex vivo canine biventricular unit using magnetic resonance imaging. A two dimensional transverse section was isolated from the solid mathematical model for regional stress analysis using p-version finite element analysis. Loading conditions and material property descriptions were taken from published reports. Analyses showed the maximum principal stresses to range from -1.76 X 10(5) to 8.52 X 10(5) dynes/cm2 during systolic loading, and from -3.85 X 10(4) to 1.13 X 10(5) dynes/cm2 during diastolic loading. This study demonstrates that magnetic resonance image-based solid mathematical biventricular models are suitable for regional stress analysis using p-version finite element analysis. p-Version finite element analysis using magnetic resonance image-based cardiac representations facilitates in vivo stress-strain analyses and may allow the clinical estimation of regional myocardial stress. PMID- 1863151 TI - Extracardiac valved conduits in the pulmonary circuit. AB - Extracardiac valved conduits represent one of the weakest facets of reconstructive surgery for congenital heart disease in that they invariably need to be replaced because of growth of the patient or because of valve or conduit failure. Between 1979 and 1989, 141 patients had 169 valved conduits placed between the heart and the pulmonary artery circuit. There were 81 male and 60 female patients, aged 2 days to 35 years (mean age, 5.9 years), with 46 patients less than 1 year of age. We performed primary repair in 117 patients; in this group, there have been 28 conduit replacements in 27 patients. In 17 patients initial repair with a conduit was performed elsewhere and we replaced these conduits in 15 and removed them in 2. A further group of 9 patients were seen after repair of tetralogy of Fallot or double-outlet right ventricle, with severe pulmonary incompetence or right ventricular outflow tract aneurysm. All had valved conduits inserted as secondary procedures. The types of valved conduits used were xenograft (n = 126) and homograft (n = 43). There were six hospital deaths (3.6%; 70% confidence limits [CL], 2% to 6%) and seven late deaths (4.1%; CL, 2.5% to 6.5%) in a total of 169 conduit insertions. Forty-five conduits have been removed and 43 reinserted without early or late mortality (0%; CL, 0% to 4%). Actuarial survival after conduit insertion was 87% at 5 years (CL, 80% to 92%), including operative mortality. Actuarial freedom from conduit replacement was 37% at 5 years (CL, 20% to 56%). Conduit insertion in infants and small children ensures subsequent replacement, but this can be done at low risk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863152 TI - Mesenchymoma of the chest wall in children. AB - Benign chest wall mesenchymoma in children is an extremely rare disease. Only 20 patients have been reported in the world literature. We report a chest wall mesenchymoma in a 2-year-old boy who was admitted to the hospital after a routine chest roentgenogram showed a mass in the right upper chest wall. The patient was asymptomatic. Clinical examination was negative, but chest roentgenograms and computed tomography showed a mass in the right upper chest wall involving the third rib. A 2 x 2 x 1.5-cm tumor was excised totally with partial resection of the third rib. The histology of the lesion corresponded to a mesenchymoma (hamartoma) of the chest wall. Our patient has been followed up for 8 years without recurrence. PMID- 1863153 TI - Neonatal pneumonectomy for isolated unilateral pulmonary artery agenesis. AB - A 23-day-old female newborn was evaluated for acyanotic respiratory distress immediately after birth. Echocardiogram and cardiac catheterization revealed absence of the right pulmonary artery. Subsequent course was complicated by necrotizing bronchopneumonia. Despite antibiotic therapy and ventilator support she failed to improve; right pneumonectomy was performed to remove the source of sepsis. This case represents an example in which an infectious complication in a rare congenital pulmonary malformation served as an indication for neonatal pneumonectomy. PMID- 1863154 TI - Role of echocardiography/Doppler in cardiogenic shock: silent mitral regurgitation. AB - Two cases of cardiogenic shock and pulmonary edema due to acute, severe, silent mitral regurgitation are discussed. The mechanism for the mitral regurgitation was papillary muscle rupture in the setting of acute myocardial infarction. Echocardiography established the presence, severity, and cause of the mitral regurgitation and the associated hyperdynamic left ventricular function in the setting of cardiogenic shock. Transesophageal echocardiography is excellent for assessing the mitral valve in critically ill patients in whom transthoracic echocardiography may be inadequate or misleading. This allowed for emergency mitral valve replacement without prolonged attempts at medical stabilization. PMID- 1863155 TI - Single-lung transplantation with atrial septal defect repair for Eisenmenger's syndrome. AB - Heart-lung transplantation has been used successfully for patients with pulmonary vascular disease but its application has been very limited due to the scarcity of donors. We report a patient with Eisenmenger's syndrome who underwent right single-lung transplantation with closure of atrial septal defect; postoperative convalescence was uneventful. Serial magnetic resonance imaging examinations demonstrate improved right heart function. PMID- 1863156 TI - Successful repair of a submitral left ventricular infected pseudoaneurysm. AB - Aneurysms of the left ventricle may be congenital or may occur after a myocardial infarction, trauma, or endocarditis. Infective endocarditis can cause destructive injury to the heart in various ways. This report describes the formation of an aneurysm of the left ventricle from trauma of a bacterial vegetation of the mitral valve. Early recognition by echocardiography and magnetic resonance imaging led to successful repair and prevented a catastrophic result. PMID- 1863157 TI - Thoracoscopic diagnosis and treatment of chylothorax after pneumonectomy. AB - Chylothorax after pneumonectomy was treated successfully by selective application of fibrin glue through a thoracoscope. Conservative therapy for 18 days failed to close the fistula. The site of leakage was identified during thoracoscopy, and fibrin glue was applied under direct vision. Leakage decreased immediately and eventually stopped completely. This technique is less invasive than standard surgical treatment and should be considered in all patients with postoperative chylothorax. PMID- 1863158 TI - Long-term bridge to transplantation with the Symbion acute ventricular assist device system. AB - A 48-year-old man was supported for 164 days with Symbion biventricular assist devices. During that time, his cytotoxic antibody screen fell from 97% positivity to less than 10%, enabling cardiac transplantation. Complications during the implantation included a 3-minute episode of amaurosis fugax, one positive blood culture, and anemia, which responded to decreased frequency of blood drawing. He is now alive 7 months after transplantation. PMID- 1863159 TI - Pulmonary origin of left anterior descending coronary artery in tetralogy of Fallot. AB - We report the case of a 4-year-old girl with an anomalous origin of the left anterior descending coronary artery from the pulmonary artery in association with tetralogy of Fallot. Creation of an intrapulmonary tunnel from a newly created aortopulmonary window to the coronary ostium in the pulmonary trunk and total repair of tetralogy of Fallot were successfully carried out. The advantage of intrapulmonary tunnel technique (Takeuchi method) for this very rare combination is stressed. PMID- 1863160 TI - Removal of massive right atrial thrombus guided by transesophageal echocardiography. AB - Formation of massive right atrial thrombi around a peritoneovenous shunt is a known complication of these devices. Removal of an obstructive right atrial thrombus requires cardiopulmonary bypass and has been associated with a high morbidity and mortality. Transesophageal echocardiography was used in this case to diagnose and guide the surgical removal of a massive right atrial thrombus. PMID- 1863161 TI - Videothoracoscopic ligation of bulla and pleurectomy for spontaneous pneumothorax. AB - A thoracoscopic technique to ligate pleural bullae and perform parietal pleurectomy is described. The procedure has been performed on 2 patients, allowing definitive treatment of recurrent spontaneous pneumothoraces. Both patients have been cured of their problem and benefited from the decreased trauma of access by reduced postoperative pain, rapid recovery, and decreased scarring of the skin. PMID- 1863162 TI - Integrated pump switch for antegrade/retrograde cardioplegia. AB - A method of centralizing management of antegrade and retrograde blood cardioplegia delivery at the heart-lung machine is described. Operation of a manually flow-directed pump switch, controlled by the perfusionist, improves safety and efficiency. PMID- 1863163 TI - Doppler miniprobe to measure arterial graft flow in coronary artery bypass grafting. AB - Using a 5 X 5-mm ultrasonographic Doppler miniprobe, the flow volume of arterial grafts (internal thoracic artery and gastroepiploic artery) was measured four times during the course of coronary artery bypass grafting. Graft flow just before sternal closure was almost equivalent to that in the preoperative phase when the anastomosis was optimal. Use of the Doppler miniprobe facilitated evaluation of the arterial graft flow pattern easily and quickly. We conclude that the Doppler miniprobe can provide helpful information for the evaluation of results of coronary artery bypass grafting in real time without necessitating any additional procedures. PMID- 1863164 TI - A new balanced operation for complex gastroesophageal reflux disease. AB - Twenty-seven patients with advanced gastroesophageal reflux disease have been treated with combined transthoracic parietal cell vagotomy and Collis-Nissen fundoplication. Gastric acid analyses (n = 20) obtained preoperatively and 6 months postoperatively demonstrated a significant late reduction in gastric acid output. Twenty-six patients (96%) have experienced relief of gastroesophageal reflux disease at a mean of 13.3 months (range, 6 to 25 months) without postvagotomy symptoms. Transthoracic parietal cell vagotomy may be considered as an adjunct to mechanical surgical control of advanced gastroesophageal reflux disease. PMID- 1863165 TI - Leonardo da Vinci and the sinuses of Valsalva. AB - Recent studies indicate that eddy currents generated by the sinuses of Valsalva play an important role in the physiologic closure of the aortic valve. This process is briefly discussed and evidence is presented that this fact was well known and elaborated upon by the renaissance artist Leonardo da Vinci. This fact is illustrated with his words and drawings. PMID- 1863166 TI - Achalasia: current evaluation and therapy. AB - The current evaluation of and therapy for achalasia are reviewed. Esophageal manometry remains the best means for diagnosing achalasia. Initial therapy can include either pneumatic dilation or esophagomyotomy. Symptomatic improvement occurs in 71% of patients after pneumatic dilation, with a risk of perforation of 1.4%. Eight percent of these patients require subsequent esophagomyotomy. Surgical procedures for achalasia can be performed through either an abdominal or a thoracic incision. Nearly all authors favoring an abdominal approach add an antireflux operation to esophagomyotomy, whereas many authors advocating a transthoracic esophagomyotomy believe that an antireflux wrap is unnecessary. Overall results for the various surgical approaches used as initial therapy are excellent, with symptomatic improvement in 89% of patients, a mortality rate of less than 1%, and development of gastroesophageal acid reflux in less than 10%. Factors governing the choice of initial therapy are discussed. PMID- 1863167 TI - Blood versus oxygenated crystalloid cardioplegia. PMID- 1863168 TI - Epicardial lead failure due to dense scarring: a solution. PMID- 1863169 TI - The Society of Thoracic Surgeons Professional Liability Survey, 1988-1989. PMID- 1863170 TI - American Medical Association/Specialty Society Medical Liability Project. PMID- 1863171 TI - Medical Injury Compensation Reform Act. PMID- 1863172 TI - Professional liability: how a trial lawyer prepares a medical malpractice case for trial. PMID- 1863173 TI - Health care 1990--a consumer perspective. PMID- 1863174 TI - The brave new world of health care. AB - We are rapidly entering into a brave new world of health care. Infinite medical demands have run smack into finite resources. We can't pay for everything but we can spend our limited resources in a much more health-effective way. We have no other alternative but to devise systems that give us maximum health to our society with our limited resources. It is time to begin this process. PMID- 1863175 TI - The perspective of the industry. AB - This article calls for the development of a process to build a national consensus to assist in developing a critically needed national health policy. The physician's role in leading initiatives for major change is emphasized. Failure of physicians to participate as advocates of change will detrimentally affect the health of the nation and diminish the level of public respect and trust. PMID- 1863176 TI - Medicare: the Canadian experience. AB - In the 1940s Canada and the United States had similar lack of structure and reimbursement for diagnostic, hospital, and physician services. In Canada over the next 40 years there evolved a complex system mandated and partially funded by the federal government, but administered and delivered through 10 provincial and 2 territorial jurisdictions. Each must negotiate with federal government on cost sharing and deal with hospital budgets and physician compensation at the provincial or territorial level. The Medical Care Act of 1966 enshrined in law the five principles of public administration, universality, comprehensiveness, portability, and accessibility, converting all medical services in Canada from a privilege to a right. Any patient participation in hospital or physician charges came under increasing political attack. In 1984 the Canada Health Act specified financial penalties in federal transfer payments to provinces that permitted any direct patient charges. While Canada has "contained" health expenditures at 8.7% of gross national product, universal access to quality care is increasingly subject to rationing. The relationship between the profession and governments hard pressed to fund escalating costs in a deteriorating economy has been one of increasingly bitter confrontations. There have been four acrimonious doctors' strikes. More optimistically, there is now an emerging recognition of society's need to have physicians actively participating with other providers and governments to create a balance between access to quality health services and both public and private funding. PMID- 1863177 TI - RBRVS report: activities of the Ad Hoc Committee for Physicians' Reimbursement. AB - The Ad Hoc Committee to study the Resource-Based Relative Value Study has been active for more than 2 years. This Committee's membership was initially appointed by The Society for Thoracic Surgeons, but was quickly expanded so as to represent virtually all this nation's surgeons practicing the specialty of cardiothoracic and vascular surgery. This address describes the general activities of the Committee since its organization. It includes: 1. A brief description of the resource-based relative value scale (RBRVS). 2. The Committee's investigation of Harvard RBRVS Phase I as it relates to our specialty. 3. The Committee's findings and resultant testimony to the federal government and the American Medical Association. 4. The genesis and conduct of an independent study of the specialty. 5. A summary of our current position with respect to federal initiatives. PMID- 1863178 TI - Results from the cardiothoracic and vascular surgery work survey by Abt Associates Inc. AB - This article presents findings from the Abt Associates survey, commissioned by The Society of Thoracic Surgeons and other cooperating organizations, used to collect data to develop a resource-based relative value scale for cardiothoracic and vascular surgery. The methodology used by Abt Associates to measure the total work of surgical procedures is described, and differences between the Abt methodology and that used in the Harvard study are highlighted. The report also compares the total work measured by the Harvard and Abt studies for several specific operations. Discrepancies in relative total work measures between the two studies are shown to result primarily from differences in the measurement of preoperative and postoperative work. Background information on responding physicians is summarized. Physicians asked to respond to the survey were randomly selected from a combined list of all members of the six cardiothoracic and vascular organizations as well as those physicians included on the American Medical Association Masterfile with a primary specialty indication of cardiovascular, general thoracic, or peripheral vascular surgery. Therefore, these data should be reasonably representative of the cardiothoracic and vascular surgery profession as a whole. Information provided includes board certification status, age, sex, practice type, reimbursement source, hours worked per week, and number of operations performed. In addition, data describe the types of hospitals at which cardiothoracic and vascular surgeons typically practice. The survey also provides data on current surgical practice. Statistics are available on the average number of various types of operations surgeons perform, and on what percentage are reoperations. Finally, the work of reoperations and emergency procedures relative to primary elective operations is compared directly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863180 TI - Address by the Secretary of Health and Human Services. PMID- 1863179 TI - Physician payment reform: update on implications for cardiac surgery. PMID- 1863181 TI - Mucinous cystadenoma of the lung. PMID- 1863182 TI - Acquired immunodeficiency syndrome and the pathologist. PMID- 1863183 TI - It is the results that count in quality assurance. PMID- 1863184 TI - Interinstitutional comparison of performance in breast fine-needle aspiration cytology. A Q-probe quality indicator study. AB - In 1989, the College of American Pathologists, Northfield, Ill, instituted a voluntary quality assurance program, called "Q-Probes," that utilized nationwide interinstitutional peer comparison. One of the anatomic pathology modules retrospectively assessed performance in fine-needle aspiration cytology (FNAC) of the breast from cytohistologic correlations that were made in 294 institutions by 988 pathologists on their own cases that were accessioned during a 6-month period. Of the 13,066 cases of FNAC, 10,751 (82%) were satisfactory for evaluation. Of these satisfactory aspirates, 3471 cases (33%) had histologic correlation, which formed the basis for determining diagnostic accuracy. Of breast aspirates, 2254 (17%) were unsatisfactory for evaluation, with the mean frequency of unsatisfactory aspirates obtained by nonpathologists (18%), ie, more than twice that of unsatisfactory aspirates obtained by pathologists (7.2%). In the diagnosis of breast cancer by FNAC, the following performance results were derived with the use of the aggregate data: 82% sensitivity of the FNAC procedure, 97% sensitivity of diagnosis, 97% specificity, 95% positive predictive value, 86% negative predictive value, and 90% efficiency. No significant difference in performance was detected when institutions were stratified by six peer group characteristics. We made the following conclusions: (1) the aggregate and median breast FNAC performance values obtained from this interinstitutional comparison of data from routine procedures performed in diverse settings in North America compared very favorably with performance from single institutions published in studies of similar design in the literature, and (2) these data may provide a reference point for participant institutions to measure future quality improvement in fine-needle aspiration of breast. PMID- 1863185 TI - Transthoracic needle aspiration. The benign diagnosis. AB - Transthoracic needle aspiration is a relatively innocuous procedure used extensively in the diagnosis of pulmonary disease. Although its sensitivity for malignancy is high, a negative (benign) diagnosis is obtained in 5% to 25% of all cases. Some of these aspirates represent the result of inadequate sampling of a malignant tumor; others, however, are derived from a truly benign process. This review briefly describes and illustrates the cytologic features of these latter aspirates in order to exemplify the wide range of benign diseases that can be identified or suspected by transthoracic needle aspiration. Familiarity with such features should help the interpreting pathologist to prevent needless respiration or thoracotomy in many patients. PMID- 1863186 TI - Hypersensitivity myocarditis. AB - Autopsy tissue specimens of 69 cases of hypersensitivity myocarditis were studied to determine drug association, spectrum of histologic findings, distribution of infiltrates, and correlation between degree of infiltrates and cardiac symptoms. Hypersensitivity myocarditis was defined by the presence of eosinophils, a mixed lymphohistiocytic infiltrate along natural planes of separation, and an absence of fibrosis or granulation tissue in areas of infiltrate. Commonly implicated drugs were methyldopa, hydrochlorothiazide, ampicillin, furosemide, digoxin, tetracycline, aminophylline, phenytoin, benzodiazepines, and tricyclic antidepressants. Histiocytes composed the predominant cell type (in addition to eosinophils and lymphocytes). Lymphocytes were predominantly T cells in 12 cases studied immunohistochemically. Small foci of myocyte necrosis were present in 37 cases, and they correlated with the degree of infiltrate. A nonnecrotizing vasculitis was present in 28 cases. The right ventricle was involved in all but three cases. Cardiac arrhythmias or unexplained death occurred in 29 patients and did not correlate with the degree of myocardial infiltrate or presence of necrosis. Eosinophils were present in the livers of 30 of 58 patients, and their presence correlated with the degree of cardiac infiltration. A causative association between histologic findings and drugs is difficult to prove because of the common usage of many of the drugs implicated, multiple drug use, and the absence of clinical criteria of hypersensitivity. Symptoms do not appear related to the degree of infiltrate. In more than half the cases, infiltrates may be missed by endomyocardial biopsy due to focality of lesions. PMID- 1863187 TI - Anomalous coronary arteries arising from the aorta associated with sudden death in infancy and early childhood. An autopsy series. AB - Anomalous coronary arteries arising from the aorta are a recognized cause of myocardial ischemia and sudden death. Death has been precipitated by exercise in most cases. We present the results of an autopsy study in which sudden and unexpected deaths associated with coronary anomalies were found in three children (less than 2 years of age). In two cases, death was not associated with exercise. In two case, the myocardium was morphologically normal, and in the third case, there was an extensive recent anterior myocardial infarct with a background of established fibrosis. Coronary artery anomalies may be easily overlooked in this age group because of small vessel size and difficulty in dissection; this is particularly so when there are normally placed ostia. One consequence of this is potential for confusion with sudden infant death syndrome. PMID- 1863188 TI - Characterization of Cobblestone mitral valve interstitial cells. AB - Mitral valve interstitial cells (MVICs) are important in the structure and function of the valve. In a cell culture system that used explants to harvest MVICs, we found that after several passages, some of the cultures at confluence formed a monolayer of cobblestone-shaped cells (CB type). The rest of the cultures were, however, different, consisting of elongated cells (EL type) that formed overlapping orthogonal patterns. When compared with the MVICs-EL, cells from cultures of MVICs-CB were less adherent to a plastic substratum initially than were MVICs-EL and were more sensitive to trypsinization following culture for 3 to 7 days. Ultrastructurally, the cultures of MVICs-CB showed prominent Golgi's complexes and endoplasmic reticulum and fewer microfilaments when compared with those of MVICs-EL. Most strikingly, the CB cells contained much less alpha-smooth-muscle cell actin compared with that of EL cells. The MVICs-CB were not endothelial cells as they did not show the characteristic dense peripheral band that was present in endothelial cells in a confluent monolayer and showed only trace amounts of fluorescence when incubated with 1,1-dioctadecyl 1-3,3,3,3 tetramethyl-indocarbocyanine-percholate (Dil-)--acetylated low-density lipoprotein compared with large amounts of fluorescence with endothelial cells. Cells that were morphologically similar to MVICs-CB were present in the in vivo valve as well and also formed small islands of cells even in the primary cultures that grew out of the explant. The findings supported the hypothesis that MVICs-CB represent a distinct phenotype of the MVICs that is different from that of the MVICs-EL and is not that of either endothelial or medial smooth-muscle cells. PMID- 1863189 TI - Coronary heart disease in rhesus monkeys with diet-induced coronary artery atherosclerosis. AB - Diet-induced coronary artery atherosclerosis develops in rhesus monkeys (Macaca mulatta). The goal of this study was to establish the rhesus monkey as an animal model of coronary heart disease (CHD). From a colony of 160 rhesus monkeys fed an atherogenic diet, we identified 14 monkeys with electrocardiographic and echocardiographic evidence of CHD. When compared with 14 rhesus monkeys matched for age, gender, and dietary history with normal electrocardiograms and echocardiograms, monkeys with CHD had higher arterial blood pressures (mean +/- SEM, 92 +/- 4 mm Hg vs 75 +/- 5 mm Hg, respectively), lower high-density lipoprotein cholesterol concentrations (mean +/- SEM, 1.70 +/- 0.25 mmol/L vs 2.32 +/- 0.28 mmol/L [66 +/- 10 mg/dL vs 90 +/- 11 mg/dl]), and lower A-l apolipoprotein concentrations (mean +/- SEM, 200 +/- 17 mg/dL vs 252 +/- 15 mg/dL). Monkeys with CHD tended to have higher total plasma cholesterol concentrations (mean +/- SEM, 11.6 +/- 1.55 mmol/L vs 9.36 +/- 0.93 mmol/L [450 +/- 60 mg/dL vs 362 +/- 36 mg/dL]) and higher low-density lipoprotein cholesterol concentrations (mean +/- SEM, 8.71 +/- 1.75 mmol/L vs 6.12 +/- 0.90 mmol/L [337 +/- 68 mg/dL vs 237 +/- 35 mg/dl]) than monkeys with normal electrocardiograms and echocardiograms. We conclude that rhesus monkeys, like human beings, develop CHD as a complication of coronary artery atherosclerosis. Furthermore, risk factors for CHD in rhesus monkeys and human beings are similar. PMID- 1863190 TI - Adenoma of type 2 pneumocytes with oncocytic features. AB - An adenoma of type 2 pneumocytes in the periphery of the left lung was an incidental finding at the autopsy of a 28-year-old woman. Light microscopy revealed a predominantly papillary growth with oncocytic features. Ultrastructurally, multilaminated bodies and many mitochondria were found in the tumor cells and tubular myelin in the extracellular spaces. Immunohistochemistry revealed surfactant apoprotein in tumor cells and extracellularly. PMID- 1863191 TI - Inverted papilloma of the urinary bladder with granular eosinophilic cells. An unusual neuroendocrine variant. AB - We report the morphologic, immunohistochemical, and electron microscopic characteristics observed in a case of an inverted papilloma that contained neuroendocrine cells resected from the urinary bladder of a 77-year-old woman. Additionally, we evaluated the incidence of neuroendocrine cells in eight cases of inverted papillomas of the urinary bladder obtained from the files of the Armed Forces Institute of Pathology, Washington, DC. To our knowledge, an in depth study of neuroendocrine cells in this neoplasm and a comparison of the same with neuroendocrine cells observed in other conditions in the lower genitourinary tract have not been previously published, prompting this report. PMID- 1863192 TI - Primary hyperaldosteronism due to a functional black (pigmented) adenoma of the adrenal cortex. AB - The clinical and pathologic findings are reported in a case of primary hyperaldosteronism due to a functional black (pigmented) adenoma of the adrenal cortex. Cortical atrophy of the involved gland was present, the mechanism of which was obscure. PMID- 1863193 TI - Rapid preparation of plasma for coagulation testing. AB - Currently recommended minimum centrifugation of whole blood to produce platelet poor plasma for routine coagulation assays is 1000g relative centrifugal force for 10 minutes. Many clinical laboratories centrifuge blood for routine coagulation assays from 500g to 2000g, with spin times varying from 20 to 5 minutes. Ninety blood samples, routinely submitted to our coagulation laboratory, were prospectively assayed simultaneously for the prothrombin time, activated partial thromboplastin time, and fibrinogen level, comparing centrifugation at 11,000g for 2 minutes with centrifugation at 1000g for 10 minutes. Routine and readily available equipment and supplies were used. Platelet counts were performed on the supernatant plasma in each sample to determine the efficacy of platelet depletion. Excellent correlation of methods was observed for the prothrombin time, activated partial thromboplastin time, and fibrinogen level. Platelet counts on the plasma supernatant showed no significant difference between the two centrifugation methods. We concluded that high-speed centrifugation at 11,000g with a shortened spin time of 2 minutes and with the use of routinely available equipment and supplies can significantly decrease the specimen preparation time for routine coagulation testing. PMID- 1863194 TI - Multisystem failure and hepatic microvesicular fatty metamorphosis associated with tolmetin ingestion. AB - Multisystem toxicity including both renal and hepatic failure has been reported with the use of nonsteroidal anti-inflammatory drugs. We report a fatal case of multisystem failure associated with tolmetin ingestion in a 15-year-old girl. Microvesicular fatty change was found in the liver at autopsy. To our knowledge, this is the first reported case of nonsteroidal anti-inflammatory drug-associated multisystem failure to have this histopathologic finding. PMID- 1863195 TI - Large-cell lymphoma presenting with hepatic sinusoidal infiltration. AB - We describe a case of large-cell lymphoma of B-cell phenotype with clinicopathologic features resembling malignant histiocytosis. The clinical presentation was characterized by fever, anemia, thrombocytopenia, coagulopathy, and elevated liver enzyme levels. These features and the finding of a predominantly sinusoidal infiltrate of neoplastic cells on liver biopsy raised the suspicion of malignant histiocytosis. The patient subsequently developed supraclavicular lymphadenopathy, which proved to be due to a diffuse large-cell lymphoma. Immunophenotypic studies performed on the lymph node and the original liver biopsy specimen established the B-cell nature of neoplastic cells at both sites. This case highlights a rare pattern of hepatic involvement by large-cell lymphoma, and contrasts the latter with other hematologic disorders associated with hepatic sinusoidal infiltrates. PMID- 1863196 TI - Granulocytic sarcoma of the ovary. An unusual case presentation. AB - We report an unusual occurrence of granulocytic sarcoma presenting as an ovarian mass in a 46-year-old woman with a history of dysplastic nevus syndrome. During workup of the ovarian mass, the diagnosis of acute myelogenous leukemia was made. A fine-needle aspirate of the ovarian mass showed granulocytic sarcoma. The patient died of complications of the acute leukemia a short time later. A postmortem examination was performed, which confirmed the nature of the ovarian mass as a granulocytic sarcoma. Material was obtained for flow cytometry, immunohistochemical and histochemical studies, and electron microscopy. Ploidy analysis of the tumor showed it to be diploid with an S phase of 4.8% and a G2 + M ratio of 0.5%. To our knowledge, there is only one previous report of a primary ovarian presentation of granulocytic sarcoma, and only four cases in which granulocytic sarcoma was diagnosed by fine-needle aspiration cytology. The association between dysplastic nevus syndrome and acute myeloid leukemia in this case is discussed with reference to a review of the metachronous association between melanoma and leukemia as described in the literature. PMID- 1863197 TI - Diffuse uterine leiomyomatosis with hemorrhage. AB - A 28-year-old woman with primary infertility and severe menorrhagia underwent a hysterectomy after failed hormonal therapy for multiple leiomyomas. The postoperative pathologic findings established the diagnosis of diffuse uterine leiomyomatosis, which demonstrated histologic, immunohistochemical, and ultrastructural similarity to leiomyomas of the uterus. The rapid growth of the tumor coincided with the administration of clomiphene citrate, an estrogenic agonist. As with the common leiomyoma, intralesional hemorrhage in this case of diffuse leiomyomatosis was associated with norethindrone acetate treatment given after the cessation of clomiphene therapy. PMID- 1863198 TI - Disease in antiquity. The case of cancer. PMID- 1863199 TI - Acute promyelocytic leukemia--molecular breakthrough. PMID- 1863200 TI - [Thiophene as a structural element of physiologically active compounds. 19. The synthesis of substituted (6H-thieno[2,3-b]pyrrol-4-yl)phenylmethanones]. AB - The synthesis of 4-Methoxyphenyl-[5-methyl-6-(2-(4-morpholinyl)-ethyl)-6H thieno[2,3- b]pyrrol-4-yl)phenylmethanone (1), a thiophene analogue of the analgesic Pravadoline B, is described. Starting with the acetylprotected thienylhydrazine 2b compound 7 was obtained in a Fischer-analogue cyclication in two steps. Use of the BOC-protected thienylhydrazine 2a yielded the pyrazol 5. Alkylation of 7 with N-(2-Chloroethyl)morpholine gave the target compound 1. In the acetylcholine-writhing-test in mice as well as in the acetic acid-writhing test in rats 1 showed a significant lower antinociceptive activity than Pravadolin (B). PMID- 1863201 TI - [Potential antiestrogens of the 1,2-diphenyl-1-pyridyl-but-1-ene type. 2. Biological testing]. AB - Z-1-(4-hydroxyphenyl)-1-(4-resp. 3-pyridyl)-2-phenyl-but-1-enes Z-1 and Z-2 and their acetates Z-1a and Z-2a are weak estrogens (uterine weight test, immature mouse), which cause a marked tumor growth inhibition on the hormone-dependent MXT mammary carcinoma of the mouse. No or just slight estrogenic side effects determined by uterine weight are detectable in this tumor experiment. PMID- 1863202 TI - Synergistic inhibition of aminopeptidase B by penicillamine or cysteine and metallic salts. AB - The inhibition of aminopeptidase B by D- and L-penicillamine and D- and L cysteine is reported. All these alpha-amino-beta-mercapto acids inhibit moderately this enzyme, with IC50 values in the 10(-4) range. This inhibition was not reversed by Zn2+ ions, but a synergistic effect was observed. A similar effect took place by the combined use of D-penicillamine and Fe2+, Ca2+ or Ni2+ salts, but not with copper salts. The zinc-D-penicillamine and zinc-D-cysteine complexes 3 and 4 show an inhibitory potency approximately 5-fold higher than that of the corresponding amino acid. PMID- 1863203 TI - Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XIV: Branched aliphatic and alicyclic triamines and tetramines. AB - Twenty-four triamines and three tetramines were synthesized. Seventeen triamines inhibited platelet aggregation induced by collagen at a concentration below 10 mumol/L (IC50). Ten triamines in a 100 mumolar concentration inhibited fibrin formation induced by thromboplastin by more then 75%. Both effects do not run parallel. They are strongly dependent from the steric and lipophilic properties of the title oligoamines. The tetramines were nearly inactive. PMID- 1863204 TI - Synthesis, antimicrobial, inotropic, and chronotropic activities of novel 1,2,4 triazolo[4,3-a]quinolines. AB - Starting from the 2-quinolylhydrazine 1 the title compounds were prepared according to Schemes 1 and 2. Some of them show activities described in the title of this paper. PMID- 1863205 TI - High-intensity focused ultrasound in the treatment of experimental liver cancer. AB - High-intensity focused ultrasound (HIFU) was used to treat Morris rat hepatoma 3924A implanted in the liver. Treatment was administered with a lens-focused 4 MHz transducer that created a focused beam of 550 W/cm2 at peak intensity. One hundred twelve rats with liver tumors were divided into two groups of 56 each. Group 1 received HIFU therapy while group 2 (the control group) did not. All rats were killed immediately or 1, 3, 7, 14, 21, or 28 days after treatment. Eight rats in each group were killed at each interval for pathologic and biochemical studies. Significant inhibition of the tumor growth was seen in the HIFU-treated group, with tumor growth inhibition rates of 65.4% to 93.1% from the third to the 28th day after treatment. Ultrasound-treated tumors showed direct thermal cytotoxic necrosis and fibrosis. An additional 56 ACl rats with liver tumors were divided into four groups of 14 each. Group 1 received doxorubicin hydrochloride intraperitoneally and HIFU therapy; group 2, HIFU therapy; group 3, doxorubicin hydrochloride; and group 4 (the control group), neither HIFU nor doxorubicin hydrochloride. Significantly improved survival rates were noted in HIFU-treated animals (groups 1 and 2) compared with those of groups 3 and 4. These data suggest that HIFU may be a useful method for local treatment of hepatic tumors. PMID- 1863206 TI - The significance of portal vein thrombosis after distal splenorenal shunt. AB - The aims of this study were to determine the incidence of portal vein thrombosis after the distal splenorenal shunt, to identify any predictive factors, and to assess the clinical significance of this complication. Preoperative and postoperative angiograms and clinical evaluation were reviewed in 124 patients who underwent distal splenorenal shunts. Total and partial portal vein thrombosis were seen on 13 (10.5%) and 22 (17.7%) postoperative angiograms, respectively. The only preoperative variable correlating with development of portal vein thrombosis was portal venous perfusion, which was significantly lower in patients with than in those without portal vein thrombosis. In six of 10 patients with postoperative pancreatitis, portal vein thrombosis developed. The frequency of early postoperative complications was significantly greater in patients with total portal vein thrombosis than in those with partial or no thrombosis. Long term follow-up has shown no significant effects of portal vein thrombosis on late ascites, encephalopathy, or survival. PMID- 1863207 TI - Acute cholangitis secondary to hepatolithiasis. AB - In a series of 88 patients with acute cholangitis secondary to hepatolithiasis, 26 (30%) required emergency therapeutic intervention because of septicemic shock (n = 15), persistent fever (n = 8), or spreading peritonitis (n = 3). Analysis was made to define factors that predisposed to failure of conservative treatment and characteristics that could predict the need for emergency biliary decompression. The age, incidence of concomitant medical diseases, previous biliary surgery, positive blood culture, bacterial strains resistant to antibiotics used, and multiplicity of bacterial strains in bile cultures in patients who required emergency intervention were similar to these factors in patients who had elective operations after successful conservative management. The incidence of intrahepatic segmental obstruction by stones or strictures was similar, but many more patients who required emergency intervention had concomitant extrahepatic obstruction due to impacted common ductal stones or strictures. Logistic regression analysis of clinical, hematological, and biochemical data showed that maximum pulse rate within 24 hours of presentation (greater than 100 beats per minute, relative risk, 2.8) and platelet count at the time of admission (less than 150 x 10(9)/L, relative risk, 5.2) were the factors with independent significance in predicting the need for emergency therapeutic procedures. This finding may serve as a guideline for identifying high-risk patients for early intervention. PMID- 1863208 TI - Intraluminal ileal recovery of pancreatic polypeptide. AB - Pancreatic polypeptide (PP) is a normal constituent of pancreatic islet cells. Enterocytes containing PP have been identified but incompletely characterized. We previously demonstrated independent intravascular and intraluminal release of two related peptides, peptide YY and neuropeptide Y. In this study, using ileal segments in conscious dogs, we evaluated the intravascular and ileal intraluminal presence of PP to test meals. Fasted plasma and recoverable ileal PP concentrations averaged 139 +/- 2 and 65 +/- 4 pg/mL, respectively. A mixed protein meal resulted in a sustained rise of circulating PP levels associated with a brief evaluation of ileal luminal PP levels. Fat meals were followed by elevations in plasma PP levels without luminal changes. Glucose ingestion altered neither plasma nor luminal PP levels. Our data support the existence of ileal PP containing cells that respond independently of circulatory PP-releasing cells to different ingested stimuli. PMID- 1863209 TI - Arterial hemorrhage after pancreatoduodenectomy. The 'sentinel bleed'. AB - Experienced centers report reduced operative mortality after pancreatoduodenectomy for cancer, but significant complications continue to occur in as many as 25% of patients. Anastomotic disruption leads to sepsis in the pancreatic bed where major vascular structures have been exposed by regional lymphadenectomy, creating a setting for arterial erosion or ligature slough and massive hemorrhage. Dehiscence of the pancreatojejunostomy is a particular risk. We treated five patients with arterial hemorrhage after pancreatoduodenectomy, all of whom had had "sentinel" bleeding from the abdominal drains or gastrointestinal tract. Results of endoscopy were misleading in two patients. Three of five patients were saved by prompt recognition, early operation, and, in one instance, angiographic embolization. Sentinel bleeding after pancreatoduodenectomy indicates local sepsis and probable anastomotic dehiscence. Recognition of its significance and prompt response may prevent exsanguination. PMID- 1863210 TI - Why I prefer not to treat trauma patients. PMID- 1863211 TI - The value of surgical history. AB - It remains a rhetorical question whether or not an understanding of surgical history is important to the maturation and continued education of a surgeon. Conversely, it is hardly necessary to dwell on the heuristic value that an appreciation of history provides in developing adjunctive humanistic, literary, and philosophic tastes. Unfortunately, modern medical historians usually hold nonmedical degrees and basically restrict themselves to research concerning medical or public health aspects of social history. Clinical surgical history is increasingly avoided because the professional medical historian has no clinical background. However, practicing surgeons, who can serve as amateur medical historians, have knowledge and experience that place them in a unique position to assess historic facts and direct surgical historic inquiry. It is my belief that if medicine were taught with a greater emphasis on the historic approach, our country's physicians would be better prepared to cope with the health care problems of the future. By increasing the number of surgeons, who as an avocation, research and write about surgical history, our ability to provide better surgical care in our nation's coming years will be enhanced. PMID- 1863212 TI - 98th annual meeting of the Western Surgical Association, Scottsdale, Arizona. November 12-13, 1990. Part II. PMID- 1863213 TI - Results of surgical therapy for biliary dyskinesia. AB - One hundred eighty-seven patients who presented with symptoms consistent with biliary colic but had no ultrasonic evidence of cholelithiasis were observed in an effort to identify those with a functional gallbladder disorder that might benefit from surgical intervention. All patients underwent quantitative evaluation of gallbladder emptying using cholecystokinin biliary scanning, and ejection fractions less than 35% were considered abnormal. One hundred twenty nine patients (69%) had abnormal ejection fractions, and 88 (68%) of these subsequently underwent cholecystectomy. Sixty of the surgical specimens revealed pathologic changes. Eighty-four percent of patients successfully contacted for follow-up experienced complete relief, and another 13% had partial relief of preoperative symptoms. Only two patients reported no change in symptom complex. Twenty-nine patients with abnormal ejection fractions elected not to undergo surgery. Fifty-nine percent of these patients continued to experience symptoms of biliary colic at a mean follow-up of 22 months. Of the 44 patients with normal ejection fractions, 35 (80%) reported resolution of symptoms during follow-up of medical treatment. Cholecystokinin biliary scanning can help identify patients with acalculous, functional gallbladder disease who may benefit from cholecystectomy. PMID- 1863214 TI - Prediction of injury caused by penetrating wounds to the abdomen, flank, and back. AB - Controversy about the appropriate evaluation of penetrating abdominal, flank, and back injuries prompted this retrospective review of 311 patients at an urban level 1 trauma center over 5 years. Seventy-five (24%) patients sustained gunshot wounds to the abdomen. All patients with gunshot wounds underwent exploratory laparotomy; results of 67 laparotomies (89%) were positive. Of 236 patients sustaining stab wounds (140 abdominal wounds, 51 flank wounds, 26 back wounds, and 19 wounds to multiple sites), 147 were treated according to a selective protocol, based on results of physical examination, wound exploration, peritoneal lavage, and ancillary diagnostic studies. No injuries were found at celiotomy in three (2%) of these 147 patients. One false-negative result of evaluation of a flank wound occurred. Significant injuries were found in 13 patients (68%) with stab wounds to multiple sites, 61 patients (44%) with abdominal stab wounds, 15 patients (29%) with flank stab wounds, and four patients (15%) with back stab wounds. Mandatory exploration of gunshot wounds is justified. Physical findings of intra-abdominal injury or positive results of peritoneal lavage identify stab wound victims likely to benefit from surgical exploration. A policy of mandatory observation or routine celiotomy for treatment of stab wounds is not justified. PMID- 1863215 TI - Modulation of IgM antibody formation by lipid peroxidation products from burn plasma. AB - Lipid peroxides (conjugated dienes) have been shown to increase in the plasma of thermally injured animals and in humans. The purpose of this study was to determine if conjugated diene-rich fractions extracted from the plasma of burned rats 3 hours after injury would alter humoral immune function in unburned animals. Plasma diene extracts from burned or normal rats were dissolved in ethanol and given intraperitoneally to Long-Evans rats. Fifteen minutes after diene injection, the rats were immunized with sheep erythrocytes. Five days later, serum and spleen cells obtained from these immunized rats were tested for IgM immunity against sheep erythrocytes. Both plaque-forming cells from spleen and hemagglutination titers in serum were significantly enhanced in the group treated with dienes obtained from the thermally injured rats. These data suggest that conjugated diene-bearing lipid fractions from burn plasma may modulate immune function and support the concept that humoral immunity is enhanced after thermal injury. PMID- 1863216 TI - Evolution of the treatment of the injured colon in the 1980s. AB - During the past 10 years, 1006 patients with colon injuries were treated in an urban trauma center. Primary repair, including suture repair and resection with anastomosis, was performed in 614 patients (61%), colostomy in 284 patients (28%), and exteriorized repairs in 83 patients (8.3%). In the remaining 25 patients (2.5%) who were exsanguinating, the colon injuries were ligated. Independent risk factors for adverse outcomes (defined as a fecal fistula, abdominal abscess, stomal complication, or death from multisystem failure) were identified using multiple logistic regression analysis. These factors were used to match patients at similar risk within different treatment groups, and odds ratios for each treatment were calculated. The odds ratios for primary repair, colostomy, and exteriorized repair were 1.0, 1.9, and 2.0, respectively. Therefore, the chance of an adverse outcome was twice as great for both exteriorized repair or colostomy as for primary repair. It is concluded that further increases in the use of primary repair are warranted. PMID- 1863217 TI - Gastric leiomyosarcoma. Prognostic factors and surgical management. AB - Information on gastric leiomyosarcoma, such as important prognostic factors, patterns of disease recurrence, and optimal methods of treatment, are derived from limited patient experience. We address these questions, with specific focus on whether an advantage could be demonstrated for radical resection compared with wide local excision, by retrospectively investigating 53 patients who underwent surgical treatment at Mayo Clinic, Rochester, Minn. Abdominal pain and/or gastrointestinal bleeding associated with an intramural or exogastric mass were typical features of this disease. Only tumor size and histologic grade were statistically significant prognostic factors. With analysis of survival curves and patterns of recurrence, neither the addition of lymphadenectomy nor the wider tumor-free margins of a radical gastrectomy seemed superior to the more conservative local excision. Therefore, wide local excision remains the preferred treatment when technically feasible. PMID- 1863218 TI - Pyogenic liver abscess. Modern treatment. AB - Historically, open surgical drainage has been the treatment of choice for pyogenic liver abscess. The records of 54 patients with pyogenic liver abscess were reviewed to determine whether earlier diagnosis with current imaging tests and definitive treatment with antibiotics, aspiration, or catheter drainage was an effective alternative to open drainage. Twenty-nine patients were treated with broad-spectrum antibiotics and diagnostic aspiration. Twenty-three (79%) recovered uneventfully, and six required catheter or operative drainage. Twenty three patients (including five who failed aspiration) underwent drainage with percutaneously placed catheters. Nineteen (83%) recovered; four required open surgical drainage. Of seven patients who required open surgical drainage, six recovered. One (2%) of the 54 patients died following failed aspiration and catheter and surgical drainage. Four patients were successfully treated with antibiotics alone without aspiration. These results confirm that pyogenic liver abscess can be successfully treated with broad-spectrum antibiotics and aspiration or percutaneous catheter drainage. Open surgical drainage is reserved for patients in whom treatment fails or who require celiotomy for concurrent disease. PMID- 1863219 TI - Failure to obtain drug-resistant variants of influenza virus after treatment with inhibiting doses of 3-deazaadenosine and H7. AB - 3-Deazaadenosine and H7 specifically inhibit influenza virus replication under conditions at which they have no effect on other tested RNA viruses. This effect can be significantly potentiated by concomitant application of both compounds. Even under the most stringent conditions we failed to obtain any drug resistant variants. A possible explanation for this failure is that these compounds presumably do not act on a viral component like amantadine which was used as a control, but they interfere with cellular enzymes (factors) absolutely essential for influenza virus replication but more or less dispensable for the survival of the cell. PMID- 1863220 TI - Sequence analysis of temperature sensitive and "neuraminidase-tolerant" mutants of Newcastle disease virus (strain Beaudette C). PMID- 1863221 TI - Canine distemper virus infection and encephalitis in javelinas (collared peccaries). AB - Canine distemper virus has been isolated in dog lymphocyte cultures from the brains of three javelinas that became moribund with signs of encephalitis. Canine distemper viral antigen was demonstrated predominantly in neurons and morbillivirus-like structures were seen by electron microscopy in brains of diseased animals. Serological studies suggest that CDV infection may be common in javelinas. PMID- 1863222 TI - Coat protein of potyviruses. 7. Amino acid sequence of peanut stripe virus. AB - The amino acid sequence of the 287-residue coat protein of peanut stripe virus (PStV) was determined from the sequences of overlapping peptide fragments. Results indicated that the amino terminus was blocked by an acetyl group, as has previously been found for the coat protein of Johnsongrass mosaic potyvirus. Comparison of the PStV sequence with coat proteins of 20 distinct potyviruses gave sequence identities of 47-57%, except for zucchini yellow mosaic virus (ZYMV), passionfruit woodiness virus (PWV), and the related strains watermelon mosaic virus 2 (WMV 2) and soybean mosaic virus-N, which showed sequence identities of 70-76%. Several amino acid residues which were common to the core sequences of these coat proteins were at positions previously found to be invariant among potyvirus coat proteins. The degree of these similarities suggests that although PStV, WMV 2, ZYMV, and PWV are distinct potyviruses, they share a common ancestor in their evolutionary development. PMID- 1863223 TI - Replication of avian influenza viruses in humans. AB - Volunteers inoculated with avian influenza viruses belonging to subtypes currently circulating in humans (H1N1 and H3N2) were largely refractory to infection. However 11 out of 40 volunteers inoculated with the avian subtypes, H4N8, H6N1, and H10N7, shed virus and had mild clinical symptoms: they did not produce a detectable antibody response. This was presumably because virus multiplication was limited and insufficient to stimulate a detectable primary immune response. Avian influenza viruses comprise hemagglutinin (HA) subtypes 1 14 and it is possible that HA genes not so far seen in humans could enter the human influenza virus gene pool through reassortment between avian and circulating human viruses. PMID- 1863224 TI - Suppression of murine leukemia virus-mediated 3Y1 cell fusion by expression of mouse MHC class I. AB - Rat 3Y1 fibroblasts transformed by adenovirus type 12 or its E1A gene formed syncytia by cocultivation with Friend murine leukemia virus (MuLV)-producing cells. On the other hand, parental 3Y1 cells and those derivatives induced by other tumor viruses or chemical carcinogen showed no MuLV-mediated syncytium formation [N. Momozaki et al. (1990) Arch. Virol. 115: 123-126]. The expression of major histocompatibility complex (MHC) class I mRNA and antigens was significantly reduced in these Ad12- and E1A-transformed 3Y1 cells. In contrast, other tumor virus-and chemical carcinogen-transformed 3Y1 cells expressed MHC class I almost in normal levels as did parental 3Y1 cells. Furthermore, Ad12 transformed 3Y1 cells which started to express the transfected exogenous MHC class I gene, H-2Ld, showed no more MuLV-mediated 3Y1 cell fusion. These results indicate that the expression of MHC class I on the cell membrane is closely related to the inhibition of 3Y1 cell fusion by MuLV. PMID- 1863225 TI - The use of serological differentiation indices for the phylogenetic analysis of plant virus relationships. AB - The potential use of serological differentiation indices (SDIs) in the phylogenetic analysis of plant virus coat protein relationships is presented. Relationship dendrograms were constructed from SDI data for viruses in the tymovirus and Subgroup I geminivirus taxonomic groups, using distance or phenetic methods embodied in the computer programmes FITCH and NJTREE. Relationship dendrograms for geminiviruses agreed well with those constructed by others from sequence or other data; the dendrogram for tymoviruses was not in agreement with one calculated from amino acid composition data, or from other properties, but appears consistent with recently-shown sequence similarities between tymoviruses. Implications of these results for the classification and taxonomy of plant viruses are discussed. PMID- 1863226 TI - Country practice. PMID- 1863227 TI - Technology complementing midwifery. PMID- 1863228 TI - What are the challenges for the next generation of midwives: 1990-onwards. PMID- 1863229 TI - The Pap test registry--an important initiative for women's health. PMID- 1863230 TI - Women's business. PMID- 1863231 TI - Round and round the mulberry bush. PMID- 1863232 TI - Ischemic cerebral vascular disease: an overview. AB - The management of patients with cerebrovascular ischemic disease (ICD) is rapidly changing due to newer diagnostic approaches and therapies being developed. In the present article, the author reviews part of his experience in the clinical and basic fields of ICD which is the most common neurologic problem leading to acute hospitalization. Clinico-anatomic categories of ICD as well as prognosis and differential diagnosis are discussed. Data from basic and research are analyzed with a main focus on their implications for clinical management. PMID- 1863233 TI - [Spasmodic torticollis and frontal meningioma]. AB - A 57 year-old man developed a spasmodic torticollis with involuntary deviation of the head to the right-side. He had a left paramedian frontal meningioma. The association of spasmodic torticollis and other movement disorders has been reported with contralateral lesions in the basal ganglia. Its occurrence in association to a frontal lesion appears to be much less frequent suggesting a possible disorder of frontostriatal connections. PMID- 1863234 TI - [Neurocysticercosis: neuropathologic study of a fatal case treated with praziquantel]. AB - The neuropathological findings in a fatal case of neurocysticercosis treated with praziquantel are reported in this paper. The extensive necrosis of the parasites besides the exuberant inflammatory response evidence the efficacy of the drug. The severe and necrotizing type of the inflammatory response to the dead parasites may have played an important role in the cause of death of this patient, by developing severe intracranial hypertension. PMID- 1863235 TI - [Cerebral infarction and edema: prognostico-evolutional evaluation by neurologic signs]. AB - The prospective study in question involves 92 patients with cerebral infarction (CI). The follow-up was carried out for 10 days with daily evaluation, and the patients were graded for the different indicators usually researched in such cases. The observations were analysed by comparing the individual indicator averages, taken over all the patients, with the global mean of all the observed values. The analysis shows that the result of the "consciousness" exam alone is the best clinical parameter to ascertain the evolution of the patient after CI. PMID- 1863236 TI - A case of cerebral sparganosis in South America. AB - Cerebral sparganosis (CS) is a parasitic infection caused by the larva of Spirometra mansonoides. Rarely it can affect the human brain. We report the case of a 24-year old man from Paraguay who suffered from seizures and headache for one year. A frontal tumor was diagnosed by CT-scan and was subsequently resected. The pathological examination revealed a larva with Sparganum characteristics. The evolution of the patient was satisfactory. As far as we know, this is the first case of CS reported in South-America. PMID- 1863237 TI - [Spontaneous intracerebral hematomas: study of 121 cases]. AB - Results are reported on the study of 121 patients committed by spontaneous intracerebral haematomas (HIE): mean age 53.4 years, 62.8% males, mean admission time of 36 hours (3 hours to 12 days) from onset; 63.5% were graded over 7 in the Glasgow scale and 81.9% were graded 3 or over in the Boterell scale. The HIE location was 45.5% in the basal ganglia, multilobar in 14.7%, lobar in 22.8%, brain stem in 4%, and cerebellum in 2%. The mean diameter was 46.6 mm (16-93) and mean area was 1422.9 mm2 (60-4818). CSF in 67 cases showed mean opening pressure of 234 mmH20 and mean protein content of 416.9 mg/dl. Treatment was conservative in 107 cases and surgical in 14; 55.8% cases survived. The majority of patients who died were graded 3 in the Boterell scale and below 9 in the Glasgow scale. It was found a statistical correlation between death and: low Glasgow and high Boterell scales grading, motor ocular nerve palsy, motor deficit, decerebration signs, bronchopneumonia, large diameter and area of hematomas. No statistical correlation was found regarding survival and treatment with dexamethasone, antifibrinolytics, anticonvulsants, antihypertensive drugs and diuretics. Use of mannitol, fall in the systolic blood pressure and surgical therapy increased the mortality rate. From 14 patients who underwent surgical drainage, 11 died. The main complication who lead to death was bronchopneumonia. A discussion is made on HIE pathogenesis, localization, present day incidence, clinical findings, death causes, size of hematomas and type of treatment used. PMID- 1863238 TI - Premenstrual seizure increase: influence of age, duration of disease, seizure frequency, previous complaint of perimenstrual accentuation, EEG and CT scan findings. AB - We selected prospectively 80 mentally healthy women at menacme age, with chronic epilepsy and at least one seizure in the month preceding this study. They underwent four EEGs weekly. CT scan of the skull was done in 57 patients (71.25%). Seven patients were excluded because they had no seizures or menses. We registered 5630 seizures during 579 regular menstrual cycles over a 30 month period. RESULTS: there was a higher incidence of seizures in the premenstrual period (p less than 0.001); age did not influence the distribution of seizures during the menstrual cycle in the group studied; patients with 11 or more years of disease showed more accentuation of premenstrual seizures than patients with 10 or less years of disease; there was no relation between the patients frequency of seizures and the occurrence of premenstrual seizures; the patients impression of the incidence of seizures not related to menstruation was not confirmed; patients with abnormal skull CT scans had more accentuation of premenstrual seizures than patients with normal exams; patients with abnormal EEGs had more premenstrual seizures than patients with normal exams. Our findings suggest that the female sexual hormones alter cerebral excitability when there is an underlying structural pathology shown by CT scan or an electrical cerebral dysfunction revealed by EEG. PMID- 1863239 TI - [Multiple sclerosis: objective criteria of diagnosis]. AB - The frequency of multiple sclerosis in Brasil is assumed to be lower than in some geographically comparable regions, but internationally available objective diagnostic criteria are not generally used. We have reviewed a number of such criteria and applied those of Poser and colleagues to all patients who could be examined specifically for this study; who had been under our care between 1982 87; with clinically satisfactory history, physical exam, ancillary investigations and follow-up; with enough information to warrant immunosuppressive therapy with azathioprine, methyl-prednisolone or cyclophosphamide. There were 35 (88%) females and 5 (12%) males, with clinically definite (85%), probable (10%) disease according to Poser and cols, as well as 2 patients with chronic progressive disease. Age at time of study was 39 +/- 11 years, age at onset had been 32 +/- 10 years, and length of history was 6 +/- 7 years (mean +/- sd). Mode of onset was a disturbance of gait in 50%, of vision in 25% and dizziness in 10%. Physical exam at time of study showed motor deficits in 92.5%, sensory in 67.5%, ocular visual in 65%, spastic bladder in 35%, and vestibulo-cerebellar disturbances in 32%. Visual evoked responses were abnormal in 65% of 31 cases, auditory in 23% of 22 cases, and somatosensory in 80% of 20 cases. This study shows that international diagnostic criteria, specifically those of Poser and colleagues are applicable in Brasil, providing clear guidelines for diagnosis of multiple sclerosis. We suggest objective diagnostic criteria form the backbone of teaching about the disease, at various levels of medical education. Their wide utilization will in due time provide conditions for epidemiological, clinical and therapeutic studies which have not as yet been carried out in this country. PMID- 1863240 TI - [Neurocysticercosis in childhood. I. Clinical and laboratory diagnosis]. AB - Clinical and laboratory findings among 34 children (age range from 15 months to 13 years) with neurocysticercosis were reviewed. The main symptoms were: intracranial hypertension, 21 cases (62%); epilepsy, 20 cases (59%); hemiplegia, 4 cases (12%). Computed tomography (CT) in 33 children showed typical brain active cysts in 26 patients (79%) and calcifications in 2 (6%). The complement fixation reaction or the indirect immunofluorescent test for cysticercus antibody were positive in CSF in 77% (20 out of 26 patients) and serum in 78% (18 out of 23 patients). CSF pleocytosis was found in 57% of the cases (15/26 patients) with eosinophil cells in 27% (7/26 patients). The most efficient diagnostic test was CT scan of the head, and was confirmed immunologically by measurement of cysticercus antibody titers in CSF and serum. PMID- 1863241 TI - [Neurocysticercosis in childhood. II. Computed tomography of 24 patients according to symptomatic and praziquantel treatment]. AB - We studied 24 children (15 months to 13 years old) which clinical, CSF and CT findings were compatible to the diagnosis of active neurocysticercosis. The patients were divided into three groups based on the type of treatment: Group I (10 patients) treated with analgesics and/or anticonvulsants; Group II (4 patients) treated with analgesics and or anticonvulsants and corticosteroids; Group III (10 patients) treated with analgesics and/or anticonvulsants, corticosteroids and praziquantel. The first patients CT scan were compared with the sequential CT scan findings (1 month to 5 years). The initial CT scan of 12 patients showed multiple active cysts, in 5 patients an isolated active cyst, in 3 patients partial calcified cysts, in 2 patients cerebral edema and in 2 patients were normal. The final results of the three groups of patients, as far as concern the normalization of CSF abnormalities or calcification of the cysts were the same, no matter the type of treatment applied to them. These results, although the small number of patients, showed that most of the children have good final results, with improvement of clinical symptoms and CT findings. We suggest that neurocysticercosis in children need multicenter study. So, a great number of patients can be followed and better definition can be established on the treatment of neurocysticercosis. PMID- 1863242 TI - [The involvement of the choroid plexus and ependyma in tuberculosis: its importance in dissemination of the disease in the central nervous system]. AB - It is reported in this paper, the study of the choroid plexus and ependyma in 42 cases of tuberculous meningitis. Granulomatous lesions were found as a very frequent lesion in the choroid plexus (75%). In some cases detached granulomas were found free among the villi. The ependymal lesions seen in 97% of the cases are characteristic of the tuberculous granular ependymitis. The report points out the role of these lesions, played in the pathogenesis of the tuberculous meningitis. PMID- 1863243 TI - [Classification of hereditary cerebellar ataxias]. AB - The hereditary cerebellar ataxias are one of the most complex group of neurogenetic diseases. A review of the several attempts do classify the heredoataxias is presented. The classifications based on clinical and genetic grounds are the most useful. The recent advances in molecular genetics are prone to give important clues for elucidation and understanding of the pathogenesis of heredodegenerative cerebellar diseases. PMID- 1863244 TI - [The connectivity between the greater occipital nerve and adjacent structures: anatomo-clinical considerations]. AB - In order to offer anatomical basis that aid for clinical interpretation of headache of cervical origin a macro-mesoscopic study of greater occipital nerve and its subcutaneous rise out site was accomplished. The authors observed that in its course this nerve delineates angles and direction shifts that can stand for critical points in etiology of occipital pain, so that in its subcutaneous rise out region both occipital artery and vein shape the vasculo-nervous bundle wrapped by sheath of fibrous connective tissue which has continuity and contiguity relation with the adjoining epimysium and perimysium. From our results, anatomo-clinical aspects are discussed. PMID- 1863245 TI - [Vagoglossopharyngeal neuralgia]. AB - Review of current opinions concerning clinical presentation, etiology, differential diagnosis and management of vagoglossopharyngeal neuralgia. Three cases are reported, treated by intracranial section of n. IX (alone in one case) and upper rootlets of n. X. In two patients no vascular compression of the nerves was observed. In one case an atheromatous elongated basilar artery was observed compressing and deforming the medulla oblongata at the entry zone of nerves IX-X. In this case, pain paroxysms recurred some weeks after surgery, and the patient underwent re-operation (microvascular decompression of the medulla) with good outcome. Clinical implications of the complex sensitive innervation of profound regions of the face and cervicofacial region are emphasized. Certain circumstances, such as gustatory pain due to sympathetic denervation of parotid gland, the neck-tongue syndrome and oropharyngeal pain by irritation of the first cervical spinal nerve (during lateral suboccipital puncture), point to the fact that in this region similar symptoms may be provoked by mechanisms involving different peripheric pain pathways. The theory of microvascular compression in the pathogeny of cranial nerve "hyperactive" dysfunctions is critically commented. PMID- 1863246 TI - [Sickle cell anemia: cerebral angiography changes]. AB - Two cases of sickle cell disease with neurological complications are described. Cerebral angiograms were performed and a characteristic moyamoya-like angiographic pattern was demonstrated. This pattern results from a compensatory vascularization which may follow occlusion of the arteries at the base of the brain in several diseases. The risks of angiography and appropriate precautions are emphasized. PMID- 1863247 TI - Weber's syndrome with recovery: CT demonstration of an end-zone infarction in the territory of the mesencephalic artery. AB - Weber's syndrome is one of the classically described brainstem syndromes. The mesencephalic artery and the syndromes resulting from occlusion of its branches have been attracting increasing interest in the past few years. We present here a case of Weber's syndrome emphasizing that (1) it is one of the major syndromes deriving from infarction in the territory of the mesencephalic artery; (2) that at least two clinical patterns of Weber's syndrome may be distinguished on the basis of the presence or lack of abnormal somnolence, mental confusion, and abulia; and (3) that each one of these patterns seems to be correlated with damage to distinct zones within the general territory of the mesencephalic artery. PMID- 1863249 TI - Mental health inquiry. PMID- 1863248 TI - [Cervicogenic headache: report of a case]. AB - It has been known for many years that headaches can originate from abnormalities in the neck. However, their clinical pictures were never sufficiently systematized, at least not in order to permit the research on their pathogenesis. Sjaastad et al. described in 1983 a group of patients with a very uniform and stereotyped headache. Attacks of mild, longlasting, unilateral head pain without sideshift, occurred every few weeks. The headache could be provoked by neck movements, such as extension, rotation or lateral flexion, as well as by external pressure towards trigger points in the neck. It usually started back in the neck, eventually spreading to the ipsilateral orbito-frontal-temporal or facial areas. The denomination "cervicogenic headache" (CH) was proposed. Its pathophysiology is presently unknown. The C2 and occipital nerve blockages eliminate the pain. We present a CH case and make some comments on its clinical picture, pathophysiology, and treatment. PMID- 1863250 TI - Using art to explore nursing students' attitudes to psychiatric hospitals and patients. PMID- 1863251 TI - Treating emotionally disturbed children and adolescents in a tertiary referral unit. PMID- 1863252 TI - The Airing Court. PMID- 1863253 TI - HIV/AIDS nursing--a national vision. PMID- 1863255 TI - Clinical nurse specialist update. PMID- 1863254 TI - Prejudice: practice: predictions. HIV/AIDS 1991 National Nurses Conference. PMID- 1863256 TI - Violence in the workplace: predictable and preventable. PMID- 1863258 TI - Estimation of individual genetic and environmental profiles in longitudinal designs. AB - Parameter estimates obtained in the genetic analysis of longitudinal data can be used to construct individual genetic and environmental profiles across time. Such individual profiles enable the attribution of individual phenotypic change to changes in the underlying genetic or environmental processes and may lead to practical applications in genetic counseling and epidemiology. Simulations show that individual estimates of factor scores can be reliably obtained. Decomposition of univariate, and to a lesser extent of bivariate, phenotypic time series may yield estimates of independent individual G(t) and E(t), however, that are intercorrelated. The magnitude of these correlations depends somewhat on the autocorrelation structure of the underlying series, but to obtain completely independent estimates of genetic and environmental individual profiles, at least three measured indicators are needed at each point in time. PMID- 1863259 TI - A zygosity questionnaire for young twins: a research note. PMID- 1863257 TI - Current perspectives on the genetics of unipolar depression. AB - Evidence regarding the heritability of unipolar depression is evaluated. The data reviewed here support the involvement of genetic factors in the etiology of unipolar depression and its suitability for independent genetic inquiry, despite our inability to identify the mode(s) of transmission or identify a candidate locus. Continued progress in testing etiologic hypotheses requires (a) clarification of the mode of transmission; (b) resolution of phenotypic and potential genotypic heterogeneity; (c) general agreement on a "gold standard" for assessment of the unipolar phenotype; (d) the continued application of available quantitative methods to take into account the effects of ascertainment bias, sex effects, cohort effects, and variable/late age at onset; and (e) incorporation of quantitative indicators correlated with liability in multivariate analysis to improve the stability/validity of phenotypic determinations in segregation and linkage analysis. We present several recommendations regarding the extension of current methodologies in human population and quantitative genetics to help resolve these issues. PMID- 1863260 TI - Genetic differences in learning behavior in honeybees (Apis mellifera capensis). AB - Workers from colonies of Cape honeybees show marked phenotypic differences in performance in proboscis extension reflex (PER) conditioning. Analysis of these differences using parthenogenetic offspring groups permitted the estimation of genotypic values and revealed a high degree of genetic variability that is evident among related as well as unrelated bees. The results obtained from related groups are of particular importance, since they demonstrated the existence of strong genetic variability among individuals of the same colony. Quantitative analysis yielded high estimates of additive genetic effects and low estimates of dominance effects. Selection of individual workers resulted in an explicit increase in genetic variance of the next generation (G1). However, selection of bees from the parthenogenetic G1 generation, which was done to obtain parthenogenetic G2 offspring, did not lead to further improvement in selection. This observation suggests that recombination of linked genes underlying proboscis extension reflex was negligible during selection in parthenogenetic groups. Taken together with further behavioral analysis (Brandes and Menzel, 1990; Brandes et al., 1988), results from these quantitative genetic experiments suggest that additive genetic factors contribute significantly to variability among individuals for associative learning. PMID- 1863261 TI - The behavioral genetics of colony defense in honeybees: genetic variability for guarding behavior. AB - Guard honeybees stand at the entrance of colonies and facilitate the exclusion of nonnestmates from the colony. In this study, we examined the hypothesis that genetic variability among individuals in colonies might explain variability in guarding activity. To do this, we cross-fostered honey bees between colonies with high-defensive responses and colonies with low-defensive responses in alarm pheromone tests. Individuals from high-defensive colonies were more likely to guard in their own colonies (controls) than cross-fostered bees from low defensive colonies. Cross-fostered high-defensive bees also were more like to guard in low-defense colonies. These results support the hypothesis that interindividual differences in guarding behavior are at least partially under genetic control. A positive correlation between number of guards and response to alarm pheromone demonstrates a link between behaviorally separated components of the overall defensive response. PMID- 1863263 TI - Behavioral comparisons of the Tsukuba emotional strains of rats (Rattus norvegicus) in three types of novel situations. AB - Tsukuba High- and Low-Emotional rats (THE and TLE), Wistar-Imamichi/Iar rats (control group for the Tsukuba Emotional rats), and F344/DuCrj rats were tested in three types of novel situations: the open field, a runway devised as a type of open field with a shelter, and an I-maze devised as a narrow runway with shelters and covers to remove rats' freezing behavior against predatory attack. The TLE was the most active, and the THE the least active in the three tests. While the F344 was inactive in the runway and the I-maze, this strain was as active as the Wistar-Imamichi in the open field. While the THE and F344 defecated frequently, the TLE never defecated. PMID- 1863262 TI - Sexual behavior in laboratory strains of Drosophila mercatorum that have spontaneously adopted parthenogenesis. AB - Three instances are described in which bisexual laboratory strains spontaneously adopted an exclusively parthenogenetic mode of reproduction, even in the presence of fertile, bisexual males. The few males produced by the parthenogenetic strains lack a Y chromosome and are sterile but, nevertheless, showed no correlated impairment of normal mating behavior. In contrast, females show a strong reluctance to accept copulation. This behavioral correlate of parthenogenesis also has been observed previously in experimentally produced parthenogenetic lines. We suggest that genetic breakdown in female mating behavior may contribute to an evolutionary stimulus that results in a selective increase in the frequency of diploidizing events in unfertilized eggs. This ultimately might lead to the origin of an exclusively parthenogenetic reproductive mode. PMID- 1863264 TI - The salting-out behavior of human plasma fibronectin and its possible correlation with heparin-induced cryoprecipitation of the protein. AB - The solubility of human plasma fibronectin in concentrated ammonium sulfate solutions was measured at pH 7.0 and varying temperatures as well as at 25 degrees C and varying pHs. The salting-out parameters, KS and beta were found to increase linearly with temperature in the range 5 degrees-50 degrees C. KS-pH and beta-pH profiles were found to have maxima at pH 7.0. The dependence of both of the solubility parameters of plasma fibronectin on temperature and pH was thus found to be anomalous. The possibility of a correlation between the heparin induced cryoprecipitation of fibronectin and the dependence of its solubility parameters on pH and temperature is considered. It is suggested that heparin induced precipitation of human plasma fibronectin at low temperatures is caused by (i) a cold effect and (ii) conformational change in the protein due to heparin binding. PMID- 1863265 TI - Antigen binding diversity of affinity purified autoantibodies against DNA. AB - Naturally occurring autoantibodies against native DNA (nDNA) in SLE sera showed diverse antigen binding characteristics. The antibodies isolated by affinity chromatography using nDNA linked to Sepharose 4B exhibited specificity towards nDNA and showed strong reactivity with DNA-psoralen photoadduct by direct binding assay and competitive ELISA. The anti-DNA antibody belong to both IgG and IgM immunoglobulin classes and their ratio was 5:1. The possible significance of altered conformation of nDNA in the etiology of SLE has been discussed. PMID- 1863266 TI - Mechanism of transient increase in intracellular concentration of free calcium ions in HL-60 cell differentiation induced by vitamin D3 and phorbol ester. AB - A promyelocytic leukemia cell line, HL-60, was induced to differentiate into monocyte-macrophage lineage cells by treatment with active vitamin D3 and phorbol esters, and into granulocyte lineage ones by retinoic acid and dimethylsulfoxide. The changes in intracellular concentration of free calcium ions ([Ca2+]i) were measured and analyzed by calcium-imaging analysis with Fura 2-AM. A significant and transient increase in [Ca2+]i was observed in active vitamin D3 and phorbol ester systems; however, no change was detected with retinoic acid and dimethylsulfoxide. This increase was due to the influx of calcium ions from outside of the cells, and L-type calcium channels were shown to mainly contribute to this influx. Protein kinase C was also shown to be involved in the increase in [Ca2+]i. PMID- 1863267 TI - Effect of phosphorylation of calmodulin on calcium binding affinity as estimated by terbium fluorescence. AB - The effect of phosphorylation of calmodulin by casein kinase 2 on the calcium binding of the former was studied by measurement of terbium fluorescence. The binding of Tb3+ to calmodulin was followed by an increase in Tb3+ fluorescence at 545 nm. The terbium fluorescence of phosphorylated calmodulin increased at a lower concentration of Tb3+ than that of non-phosphorylated calmodulin, indicating that Tb3+ binding affinity of calmodulin was increased by phosphorylation. Our results suggest that the interaction between calcium and binding domain becomes stronger by phosphorylation. PMID- 1863268 TI - Diadenosine polyphosphates inhibit the action of ribonucleotide reductase on ADP. AB - Using permeabilized cells prepared according to Lammers, M. and Follmann, H. (Arch. Biochem. Biophys. 244, 430-438, 1986), the ribonucleotide reductase (EC 1.17.4.1) of yeast was assayed in situ. In our experimental conditions, 40-200 pmoles of ADP were reduced in 10 min per 5 x 10(7) cells. Concentrations of 0.01 mM of diadenosine tri, tetra, penta and hexaphosphates elicited inhibitions of 37, 40, 63 and 58%, respectively. The enzyme was almost completely inhibited in the presence of 0.05 mM diadenosine pentaphosphate. As some of these dinucleotides are present in yeast cells at these concentrations, the reported inhibition may have physiological meaning. PMID- 1863269 TI - Effect in vivo of atrazine on haematology and O2 consumption in fish, Tilapia mossambica. AB - Studies were conducted on haematological constituents such as Red blood cells (RBC), White blood cells (WBC), Haemoglobin (Hb), Packed cell volume (PCV), Mean cell volume (MCV), Mean corpuscular haemoglobin (MCH), Mean corpuscular haemoglobin concentration (MCHC), Blood volume (BV), Blood water content (BWC) and Whole animal oxygen consumption (WAOC) in the fish exposed to sublethal concentration of atrazine. Significant changes were seen in the constituents of the blood and O2 consumption of fish suggesting the existence of respiratory distress in the fish as a consequence of atrazine toxicity. PMID- 1863270 TI - Fatty acid composition and dynamics of phospholipids from hake (Merluccius hubbsi) spinal cord and brain and sea bass (Acanthustius brasilianus) brain. AB - This work studies the phospholipid and fatty acid composition in hake brain and spinal cord and in sea bass brain. Fluorescence anisotropy of phospholipid vesicles labeled with 1,6-diphenyl hexatriene was measured to investigate the associated dynamic properties. In all tissues studied, phosphatidylcholine and phosphatidylethanolamine were the major constituents with minor contributions of phosphatidylserine, phosphatidylinositol and sphingomyelin. Fatty acids belong to the n-9 and n-3 series exclusively. Phosphatidylinositol from hake spinal cord and phosphatidylethanolamine and phosphatidylserine from hake brain contain the greatest percentages of eicosa-5,8,11,14,17-pentaenoic (20:5) and docosa 4,7,10,13,16,19-hexaenoic (22:6), respectively. For all fractions studied the total content of saturated fatty acids increases in the order of hake spinal cord, hake brain, sea bass brain together with a decrease in the sum of monounsaturated fatty acids. The comparison between fluorescence anisotropy values and fatty acid composition clearly demonstrates that saturated acids and 20:5 and 22:6 exert a rigidizing effect. PMID- 1863271 TI - The edema inducing activity of phospholipase A2 enzymes. AB - The edema inducing activity of phospholipase A2 (PLA2) enzymes from snake venoms and porcine pancreas was investigated using mouse paw as experimental model. All ten PLA2 enzymes exhibited potent edema inducing activity. PLA2, however, is generally not the major edema inducing component of snake venom. Chemical modification studies indicated that enzymatic activity of PLA2 was required for its edema inducing activity. All PLA2 enzymes examined displayed a rapid onset edema which was suppressed by pretreatment of the mice with antihistamine. Dexamethasone pretreatment also inhibited edemas elicited by some PLA2 enzymes. PMID- 1863272 TI - Involvement of lactoperoxidase in the peroxidative degradation of serotonin: a potential pathway for indolaminergic melanin formation. AB - The peroxidase-catalyzed degradation of 5-hydroxytryptamine (serotonin) was studied using rapid scan or conventional spectrophotometry for detection of one electron conversions of enzyme compounds I, II and III. The spectral changes of serotonin during oxidation and spectral and bleaching properties of reaction products were examined. The results of the investigation clearly indicate the ability of serotonin to function as an electron donor substrate for animal peroxidases. PMID- 1863274 TI - The effect of diet upon the fatty acid composition of cranial and spinal nerve lipids. AB - The possible basal differences in lipid class and fatty acid composition between a cranial nerve (the trigeminal nerve) and two spinal nerves (the ulnar and sciatic nerves) as well as the effects of dietary lipids on the same nerves were studied. A basal (BD) and four experimental diets containing respectively hydrogenated coconut oil (HCO), grapestone oil (GSO), olive oil (OO) and linseed oil (LSO) were used. Trigeminal lipids fatty acid composition differs significantly from sciatic and ulnar ones in the percentages of 16:0, 16:1, 18:0, 18:2 n-6, 20:0, 20:1, 20:4 n-6, 24:0, 24:1 and 22:6 n-3. Also the proportions of triacylglycerols and free cholesterol strongly differ in trigeminal and spinal nerves whereas no significant difference was detected between ulnar and sciatic nerve lipids. Following the administration of the four experimental diets for 60 days, no significant change was observed in the fatty acid pattern of trigeminal lipids while the spinal ones showed a significant increase in the proportions of the fatty acids present in large quantities in the dietary oils used (i.e.: oleic acid in the OO samples). These changes are probably linked with the rapid metabolic turnover of triacylglycerols, present in larger amounts in spinal nerve lipids. PMID- 1863273 TI - Unspecific inhibition by the calmodulin antagonist calmidazolium and the intracellular calcium antagonist TMB-8 of the actions of sympathetic hepatic nerves and noradrenaline on glucose balance and flow in perfused rat liver. AB - In perfused rat liver hepatic nerve stimulation (10 Hz, 2 ms) (NS) increased glucose and lactate output, decreased flow and was accompanied by an overflow of noradrenaline into the hepatic vein. These effects were dependent on extracellular and partly on intracellular calcium. Infusion of noradrenaline (1 microM) (NA) elicited similar effects. 1) Calmidazolium at 1, 2 and 5 microM caused an increase in basal glucose output and a decrease and intrahepatic redistribution of flow after a lag of 30, 20 and 5 min, respectively. 2) After 5 min of 1 microM calmidazolium, i.e. before it altered basal metabolism and flow, the actions of NS and NA remained unaltered. 3) After 40 min of 1 microM calmidazolium, i.e. after it had just begun to alter basal metabolism and flow, NS caused a decrease in glucose and lactate output rather than an increase and the metabolic effects of NA were strongly reduced whereas the hemodynamic changes of both stimuli were not altered. 4) TMB-8 at 25, 50 and 100 microM caused a transient increase in lactate output and a decrease and intrahepatic redistribution of flow after a lag of 5 min only at 100 microM concentrations. 5) The effects of NS were inhibited already by 25 microM TMB-8 which reduced NA release whereas the effects of NA were not influenced. Thus, calmidazolium and TMB-8 did not act as a calmodulin and intracellular calcium antagonist, respectively, but had unspecific "side effects" in the complex system of the perfused liver. The antagonists cannot be used to study the role of intracellular calcium in intact organs. PMID- 1863275 TI - Nuclear glycoproteins in higher vertebrates. AB - Nuclear glycoproteins recognized by Concanavalin A have been isolated from pig, rabbit and chicken tissues. Mono and bidimensional electrophoresis patterns of proteins loosely and tightly bound to DNA have been examined. The tissue specificity rather than species-specificity appears to be a quite general property of these proteins, suggesting for them a role in the mechanism of regulation of chromatin functions. PMID- 1863276 TI - The peroxidase-catalyzed oxidation of kyotorphins. AB - In vitro experiments are reported showing that the dipeptides Tyr-L-Arg (kyotorphin) and Tyr-D-Arg (D-Arg-kyotorphin) can be oxidized by H2O2-horseradish peroxidase system: the products formed are characterized by absorption spectra with two peaks at 290 nm and 315 nm. The effects of substrate and enzyme concentration on the oxidation rate are described. Amino acid analysis of hydrolysates of peroxidase-treated kyotorphins provides evidence for the presence of dityrosine. The data suggest that the oxidation leads to the production of dimers with an o,o-linkage between the tyrosine residues. PMID- 1863277 TI - Competitive effect of anti-HLA class I monoclonal antibody (01.65) and N-N staurosporine on prolipherative response of PHA activated T-lymphocytes. AB - N-N-Staurosporine (STAR) inhibits in a dose dependent manner Tritiated-Thymidine (3H-TdR) incorporation in phytohemagglutinin (PHA) activated Peripheral Blood Mononuclear Cells (PBMC) treated with anti-HLA class I monoclonal antibody (MAb) 01.65 and its effect results competitive with MAb 01.65. Cytosolic and particulate Protein Kinase C (PKC) have been studied. Only when PKC particulate activity is no more detectable, the effect of STAR on 3H-TdR incorporation is evident. PMID- 1863278 TI - Inactivation of enolase from carp (Cyprinus carpio) muscle by 2,3-butanedione. AB - Enolase from white muscle of carp (Cyprinus carpio) is inactivated by 2,3 butanedione in borate buffer. Magnesium ions as well as substrate--2 phosphoglycerate markedly altered the rate and extent of inactivation. The partially inactivated enzyme shows unaltered Km but decreased Vmax after 10 min incubation with butanedione, however after 60 min incubation the Km value increased 2.5 fold. PMID- 1863279 TI - Statistical analyses of enzyme inhibitor kinetics: a hierarchical model-dependent approach. AB - Inference of the nature of an enzyme inhibitor and calculations of inhibitor constants from linear plots are prone to be unreliable when experimental error is significant. This may be minimised by a method of statistical analysis using nonlinear regression methods and modelling using the variance ratio test of a hierarchy of models of inhibitor behaviour. PMID- 1863280 TI - [Study of the structural-energy aspects of complementary-addressed modifications of nucleic acid with reactive 4-]N-methyl-N-(2-chloroethyl)-amino]benzyl-3'- or 5'-phosphamide oligonucleotide derivatives by a molecular mechanics method]. AB - Calculations of probabilities of the complementary addressed modification of target NA by 3'- or 5'-reactive derivatives of oligonucleotides carrying a 4-[N (2-chloroethyl)-N-methyl]aminobenzyl group attached to the 3'- or 5'-terminal phosphates through a phosphoroamide linkage have been made. It is shown that the structural basis of the high efficiency and positional specificity depending on the NA target base sequence is the extent of structural correspondence of the energetically optimal conformation of the active group in the complex to the mutual arrangement of the active group and nucleophilic site needed for the chemical reaction. The 3'-derivative has the highest dependence of efficiency and positional specificity of the alkylation on the target NA base sequence. The maximal positional specificity of the alkylation is found for the modification of the cytidine at the first position from the terminal complementary base pair at the 5'-end of the target NA. For the 5'-derivative, the alkylating ability was determined to depend on the insertion of additional methylene bridges into the standard phosphoroamide linker: two methylene groups provide for the maximal increase of the modification ability of the nucleophilic site of the target NA in the double-stranded part of the complex. The efficiency of alkylation of the target NA in a three component complex with oligonucleotide-effector also complementary to the target NA have been studied. It was found that formation of the three-component complex lead to an additional stabilization of the conformation needed for the reaction of the active group, in comparison with two component complex, by means of the intercalation of the phenyl group of the reagent in the gap between the oligonucleotide derivative and the oligonucleotide effector. PMID- 1863281 TI - [Study of the structural-energy aspects of complementary-addressed modifications of nucleic acids by reactive oligonucleotide derivatives having a 4-[N-methyl-N (2-chloroethyl)amino[benzylidene group at the 3'end by a molecular mechanics method]. AB - Calculations of probabilities of the complementary addressed modification of a target nucleic acid by derivatives of oligonucleotides carrying a 4-[N-(2 chloroethyl)-N-methyl]aminobenzylidene group attached to the 3'-end (3'-BDO) have been made. The results show that the complementary complex of a target NA with 3' BDO having R-configuration of carbon atom of the dioxalane ring is more stable than the complex including the S-stereoisomer. The S- and R-epimeres of 3'-BDO have essentially different positional abilities for alkylation of the target. The R-epimer alkylates best of all the third base of the target NA from terminal complementary pair of the complex. The S-epimer has another site the most sensitive to alkylation, which is a terminal complementary base of the target NA or the adjacent nonpaired base. Formation of the alkylation complexes are accompanied with a loss or a breakdown of hydrogen bonds in the terminal complementary base pair, thus decreasing the efficiency of alkylation. The modelling results are considered along with experimental data on modification which therefore can be interpreted on the fundamental structural level. PMID- 1863282 TI - [Affinity chromatography of DNA fragments and oligonucleotides blocked by internucleotide phosphates]. PMID- 1863283 TI - [Use of a temporary protective group during the synthesis of oligonucleotides with an unnatural bond]. AB - Methoxygroup has been used for transient P-protection on H-phosphonate oligonucleotide synthesis. Whereas other H-phosphonate linkages can be irreversibly transformed into phosphoramidates by treatment with alkylamines, the protected phosphoralkoxyl groups generate natural phosphodiester linkages after the final deprotection. The method allows for synthesis of oligonucleotides with addressed position of internucleotide phosphoralkylamidate groups. PMID- 1863284 TI - [Structure of the carbohydrate chain of riboflavin-binding glycoprotein from hen egg white. Neutral oligosaccharides of the hybrid type]. AB - Reductive cleavage of the riboflavin-binding glycoprotein from hen egg white with LiBH4/tert-BuOH followed by NaBH4 treatment gave rise to oligosaccharide alditols. After fractionation by HPLC two individual oligosaccharide alditols of a hybrid type were isolated. Their structures were proved by 1H NMR 500 MHz spectroscopy and methylation analysis. One of the oligosaccharides has earlier been found in ovalbumin, whereas the other is identified in glycoproteins for the first time. PMID- 1863285 TI - [Structure of the O-specific polysaccharide chain of the Yersinia pseudotuberculosis lipopolysaccharide (serovar II C)]. AB - An O-specific polysaccharide has been isolated on mild acid hydrolysis of lipopolysaccharide from Yersinia pseudotuberculosis serovar IIc and shown to consist of abequose, D-mannose and 2-acetamido-2-deoxy-D-galactose residues in the ratio 0.8:3:1. From the results of acid hydrolysis, 13C NMR, methylation and periodate oxidation studies the structure of the repeating unit of the O-specific polysaccharide is deduced as follows: (formula; see text) PMID- 1863286 TI - [Nucleotide sequence of bacteriophage T4 baseplate gene 26]. PMID- 1863288 TI - ABC of antenatal care. Medical problems in pregnancy--I. PMID- 1863289 TI - Bone mass in an urban and a rural population: a comparative, population-based study in southern Sweden. AB - Several previous studies have reported regional differences in the incidence of hip fractures. A population-based study was performed in the city of Malmo (urban population) and in the municipality of Sjobo (rural population), 60 km apart. A total of 961 men and women, randomly selected and of Scandinavian ethnic background, participated in the study. Bone mineral content (BMC) of the forearm was measured with single-photon absorptiometry (SPA). Women and men in the city had significantly lower BMC compared with the rural population. The differences were even more pronounced when comparing a true urban population (lived their entire life in a city) with a true rural population (never lived in a city). The differences in BMC between Malmo and Sjobo were more obvious in men. These data suggest that differences in bone mass between an urban and a rural population could to some extent explain differences in fracture incidence. PMID- 1863287 TI - Dynamic interplay between two copper-titrating components in the transcriptional regulation of cyt c6. AB - The algal plastidic cytochrome c (cyt c6) is a biochemical equivalent of the copper-containing protein plastocyanin in photosynthetic electron transfer. But generally, cyt c6 accumulates and functions only under conditions (e.g. Cu deficiency) where holoplastocyanin cannot be synthesized. In studying the regulation of Chlamydomonas reinhardtii cyt c6 expression by Cu we have determined that repression of cyt c6 accumulation occurs at the transcriptional level, and specifically in response to Cu as the metal ion regulator. Complete and sustained repression of cyt c6 transcription requires approximately 9 x 10(6) Cu ions in the medium/cell. Based on the estimated plastocyanin content of algal cells (8 x 10(6) molecules/cell) and the observation that lower ratios of Cu per cell result in only transient repression of cyt c6 transcription, we propose that Cu-dependent transcriptional repression of the gene encoding cyt c6 requires a Cu binding factor which is titrated by Cu only after the alternate electron transfer catalyst, plastocyanin, has accumulated to the stoichiometry required for photosynthesis. The precise and highly metal-specific, autoregulatory control of cyt c6 levels--directly by Cu, and indirectly by holoplastocyanin--is in keeping with the functional role of cyt c6 as an alternate, although perhaps less preferred, electron transfer catalyst. PMID- 1863290 TI - Studies on the constituents of Luffa acutangula Roxb. I. Structures of acutosides A--G, oleanane-type triterpene saponins isolated from the herb. AB - From the herb of Luffa acutangula ROXB. (Cucurbitaceae), seven oleanane-type triterpene saponins, acutosides A--G, were isolated and their structures were determined. Acutoside A is oleanolic acid 3-O-beta-D-glucopyranosyl-(1----2)-beta D-glucopyranoside. Acutosides B, D, E, F and G have a common prosapogenin structure, acutoside A, and only differ in the structures of the ester-linked sugar moieties. Acutoside B is a 28-O-[O-beta-D-xylopyranosyl-(1----4)-O-alpha-L rhamnopyranosyl-(1----2) -alpha-L-arabinopyranosyl] ester, D is a 28-O-[O-beta-D xylopyranosyl-(1----3)-O-beta-D-xylopyranosyl-(1----4)-O- alpha-L-rhamnopyranosyl (1----2)-alpha-L-arabinopyranosyl] ester, E is a 28-O-[O-alpha-L-arabinopyranosyl (1----3)-O-beta-D-xylopyranosyl-( 1----4)-O-alpha-L-rhamnopyranosyl-(1----2) alpha-L-arabinopyranosyl] ester, F is a 28-O-[O-beta-D-xylopyranosyl-(1----3)-[O beta-D-xylopyranosyl-(1----4)-O -alpha-L-rhamnopyranosyl-(1----2)-alpha-L arabinopyranosyl] ester, and G is a 28-O-beta-D-xylopyranosyl-(1----3)-[O-alpha-L arabinopyranosyl-(1- ---3)-O-beta-D-xylopyranosyl-(1----4)]-O-alpha-L- rhamnopyranosyl-(1----2)-alpha-L-arabinopyranosyl] ester. Acutoside C is a machaelinic acid (=21 beta-hydroxyoleanolic acid) saponin having the same sugar moiety as that of acutoside B. PMID- 1863292 TI - Fishhook injuries: a prospective evaluation. AB - A prospective study was conducted involving 100 nonrandomized, consecutive patients who suffered fishhook injury during the summer of 1990 in Alaska. Time of injury prior to admission to the emergency department, location of fishhook, method of removal, wound care, systemic antibiotic prophylaxis, anesthetic, tetanus immunization status, fishhook size, and complication rate were evaluated. Results of this study suggest that most fishhook injuries involve the hands or head and that postremoval wound care including oral antibiotic therapy may not be critical. Local anesthetics and simple removal techniques are adequate for nearly all fishhook injuries. Routine systemic antibiotic prophylaxis is not necessary for uncomplicated soft tissue injury due to fishhooks not involving cartilage or tendons. PMID- 1863291 TI - pH modulation of the kinetics of rabbit jejunal, brush-border folate transport. AB - In jejunal brush-border membrane vesicles, an outwardly directed OH- gradient (in greater than out) stimulates DIDS-sensitive, saturable folate (F) uptake (Schron, C.M. 1985, J. Clin. Invest. 76:2030-2033), suggesting carrier-mediated folate: OH exchange (or phenomenologically indistinguishable H+: folate cotransport). In the present study, the precise role of pH in the transport process was elucidated by examining F uptake at varying pH. For pH gradients of identical magnitude, F uptake (0.1 microM) was greater at lower (pHint/pHext: 5.5/4.5) compared with higher (6.5/5.5) pH ranges. In the absence of a pH gradient, internal F trans stimulated DIDS-sensitive 3H-folate uptake only at pH less than or equal to 6.0. Since stepwise increments in internal pH (4.5----7.5; pHext = 4.5) stimulated F uptake, an inhibitory effect of higher internal pH was excluded. In contrast, with increasing external pH (4.35----6.5; pHint = 7.8), a 50-fold decrement in F uptake was observed (H+ Km = 12.8 +/- 1.2 microM). Hill plots of these data suggest involvement of at least one H+ (OH-) at low pH (monovalent F- predominates) and at least 2 H+ (OH-) at high pH (divalent F-2 predominates). Since an inside-negative electrical potential did not affect F uptake at either pHext 4.55 or 5.8, transport of F- and F-2 is electroneutral. Kinetic parameters for F- and F-2 were calculated from uptake data at pHext 4.55 and 5.0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863293 TI - Evaluation of two rapid screening assays for the detection of human immunodeficiency virus-1 infection in emergency department patients. AB - In order to determine the sensitivity and specificity of two rapid human immunodeficiency virus (HIV-1) assays compared with enzyme immunoassay and Western blot and to assess their potential use for routine screening in an emergency department (ED), we analyzed sera from 492 consecutive ED patients using an identity-unlinked design. Sera were analyzed for HIV-1 by standard enzyme-linked immunosorbent assay and Western blot and two rapid assays: the Abbott Testpack HIV-1 (Abbott Labs, Inc, Abbott Park, IL) and the HIV-1 Genie, (Genetic Systems, Seattle, WA). Seroprevalence of HIV-1 among 492 samples was 5.1%. Both rapid assays were easy to perform and required approximately 10 minutes per test. Sensitivity and specificity of both rapid assays were 100% and 99.8%, with positive and negative predictive values of 96.2% and 100%, respectively. It was concluded that both rapid assays showed high concordance with standard enzyme-linked immunosorbent assay and Western blot. Since the ED is often the primary care setting for many patients at risk for HIV-1, the ED may be an optimal site for routine HIV-1 screening. Rapid assay screening may provide the opportunity for timely identification of HIV-1-infected patients, allowing earlier treatment and counseling. However, ethical and practical questions regarding appropriate application of rapid HIV-1 testing in EDs still needs resolution. PMID- 1863294 TI - Is the anteroposterior cervical spine radiograph necessary in initial trauma screening? AB - The usefulness of the anteroposterior (AP) radiograph of the cervical spine in contributing to the diagnosis of cervical spine injuries in the acute trauma patient was examined in a retrospective study. All cases of cervical spine fracture or dislocation seen at a level I trauma center over a 3-year period and at a rehabilitation center over a 10-year period were reviewed. The lateral radiograph, open-mouth odontoid radiograph, and AP radiograph of each case were sequentially examined by a neuroradiologist (blinded to the original diagnosis) to determine the contribution of each view in making a diagnosis of cervical spine injury. Results of these reviews showed that there were no cases of cervical spine injury evident on the AP view without an obvious corresponding abnormality on the lateral or open-mouth view. It was concluded that the AP view could be dropped from the initial screening radiographic study of the cervical spine in the trauma patient. Only an adequate lateral view and open-mouth odontoid view would then be necessary to initially evaluate the cervical spine in the trauma patient, and decisions to obtain further studies could be based safely on only the lateral and open-mouth views. PMID- 1863295 TI - Plasma norepinephrine concentrations during resuscitation in the dog. AB - The objective of this study was to evaluate whether the adrenal glands contribute to the increase in plasma norepinephrine concentrations during cardiopulmonary resuscitation, by releasing norepinephrine and/or by secreting epinephrine that facilitates the release of norepinephrine from sympathetic nerve endings via stimulation of presynaptic beta receptors. The experiments were performed in adrenalectomized and in sham-operated dogs. In adrenalectomized dogs the increase in plasma norepinephrine concentrations during cardiopulmonary arrest and basic life support (BLS) was markedly smaller than in sham-operated dogs. Intravenous infusion of physiologic doses of epinephrine during BLS in adrenalectomized animals did not influence the plasma norepinephrine concentrations. These data indicate that, as suggested by others, the marked increase in plasma norepinephrine concentrations during BLS in dogs is mainly of adrenomedullary origin. They also suggest that presynaptic facilitation of norepinephrine release by epinephrine is not important, but further experiments using higher doses of epinephrine are necessary. PMID- 1863296 TI - Asthma in the emergency department: impact of a protocol on optimizing therapy. AB - The objective of this study was to evaluate the impact of a simple educational intervention on the prescribing habits of internal medicine residents in the treatment of acute asthma in a busy emergency department (ED). Prescribing habits for 16 residents were documented for 4 months. The first 2 months served as a control period during which eight residents managed asthma patients without the benefit of any specific educational intervention beyond standard department protocols. A total of 129 patients treated by the residents during this initial phase were assessed. During the second 2-month period, a 10-minute verbal presentation and explicit written treatment protocol were provided to another eight residents, and their treatment of 83 patients was covertly evaluated. Increased prescribing of desired therapy was significantly improved in every area except that of prescribing an inhaled steroid metered dose inhaler for use as a discharge medication. The 10-minute verbal presentation given in conjunction with a three-page handout was found to be highly effective for eliciting improvement in treatment practices during short clinical rotations. The duration of this effect beyond each rotation is unknown. This educational intervention should be presented by the ED medical director, clinical pharmacist, or other appropriate clinician in virtually any ED as quality of patient care can be dramatically improved. PMID- 1863297 TI - External cardiopulmonary resuscitation preserves brain viability after prolonged cardiac arrest in dogs. AB - Standard external cardiopulmonary resuscitation (CPR) steps A-B-C produce a low blood flow that may or may not preserve brain viability during prolonged cardiac arrest. A dog model was used with ventricular fibrillation (VF) of 20 minutes, reperfusion with brief cardiopulmonary bypass, controlled ventilation to 20 hours, and intensive care to 96 hours. A retrospective comparison was made of the results of one series, now called "group I" (n = 10)--which received CPR basic life support interposed from VF 10 to 15 minutes, and CPR advanced life support with epinephrine (without defibrillation) from VF 15 to 20 minutes--to the results of another series, now "control group II" (n = 10)--which received VF no flow (no CPR) for 20 minutes. All 20 dogs within protocol were resuscitated. All 10 of group I and 7 of 10 of group II survived to 96 hours. Pupillary light reflex returned after the start of cardiopulmonary bypass at 7.7 +/- 3.7 minutes in CPR group I, versus 16.3 +/- 7.4 minutes in control group II (P = .032). At 96 hours postarrest, final overall performance categories (1, normal; 5, brain death) were better in group I. Six of 10 dogs achieved normality (overall performance category 1) in group I, as compared with none of 10 in group II (P = .004). Final neurologic deficit score (0%, best; 100% worst) was lower (better) in group I (15% +/- 20%) than in group II (51% +/- 6%; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863298 TI - Airbag-mediated corneal injury. AB - This is the first report of airbag-induced facial and corneal abrasions associated with several weeks of blurred vision in a patient without previous visual or ocular problems. Similar episodes of minor trauma from airbags are becoming commonplace, reflecting the increasing popularity of these lifesaving devices. Nonetheless, airbag-associated injuries, especially facial and ocular injuries, should be monitored and reported to both increase physician awareness and to determine if further airbag design improvements are necessary. PMID- 1863299 TI - Recurrent pneumoperitoneum following vaginal insufflation. AB - The authors report a case of a 24-year-old nulligravida woman who presented to the hospital with complaints of severe abdominal pain and radiographic evidence of pneumoperitoneum. She had two prior nondiagnostic laparotomies for similar complaints and radiographic findings. After a careful sexual history was taken the patient revealed that she had sexual intercourse preceding every similar episode including this one, during which her partner forcefully blew air into her vagina. Pneumoperitoneum associated with vaginal insufflation has been previously reported in two multigravida patients with and without anatomic abnormalities. When pneumoperitoneum is present in the absence of gastrointestinal symptoms or trauma, a meticulous sexual history should be made to avoid unnecessary laparotomies. PMID- 1863300 TI - Systemic anaphylaxis after ingestion of a psyllium-containing breakfast cereal. AB - Allergic reactions have been described as an occupational hazard among nurses and pharmaceutical workers who handle psyllium-containing laxatives. This study reports the case of a 38-year-old female nurse who ingested a bowl of psyllium containing Heartwise Cereal (Kelloggs, Battle Creek, MI) and 25 minutes later developed severe systemic anaphylaxis manifested by hypotension, a feeling of constriction in the throat, hoarseness, dyspnea, wheezing, generalized pruritus, urticaria, and vomiting. She was treated with epinephrine, normal saline, diphenhydramine, and methylprednisolone, and recovered completely. Subsequent IgE immunoblot assay was strongly reactive to psyllium. Ingestion of psyllium containing breakfast foods by sensitized individuals can be associated with life threatening systemic anaphylaxis. PMID- 1863301 TI - Cervical anterior spinal artery syndrome associated with cardiopulmonary arrest. AB - Nontraumatic spinal cord ischemia is uncommon, especially when the cervical cord is involved. We present an elderly man who sustained acute occlusion of the anterior spinal artery at a high cervical level. This was followed by a respiratory arrest due to the paralysis of the diaphragm and chest wall muscles. A review of the vascular supply to the cord and of nontraumatic ischemic myelopathy is provided. PMID- 1863302 TI - An unusual case of hoarseness and partial airway obstruction. PMID- 1863303 TI - Herniated cervical disk presenting as ischemic chest pain. AB - Myocardial ischemia must be the first concern of every emergency physician in evaluating chest pain in the adult patient. Any suspicion of myocardial ischemia must be promptly evaluated and admitted. The American College of Emergency Physicians has recently published a standards document on the care of chest pain in the adult patient. The emergency physician must be familiar with this document. Once myocardial ischemia and other life-threatening causes are ruled out, one can consider that cervical disk disease may be the cause of chest pain. The authors present two cases of patients who presented to the Emergency Department with signs and symptoms consistent with cardiac ischemia. Both patients were found to have herniated cervical disks. Subsequent surgical repair completely relieved their symptoms. Evaluation of the literature reveals that this entity was well described from 1950 to the 1960s. Most recent discussions do not mention disk herniation as even an infrequent cause of chest pain. If there is no life-threatening disease present, one should consider cervical disk disease. PMID- 1863304 TI - 1990 annual report of the American Association of Poison Control Centers National Data Collection System. PMID- 1863305 TI - Air medical transport: an annotated bibliography of the recent literature. The Society for Academic Emergency Medicine E.M.S. Committee. PMID- 1863306 TI - Container residue of activated charcoal products. PMID- 1863307 TI - Primary board status: only the end of the beginning. PMID- 1863308 TI - Emergency medical service safety of helicopters. PMID- 1863309 TI - "Asymptomatic" hyponatremia. PMID- 1863310 TI - Ruptured abdominal aortic aneurysm presenting as bilateral symptomatic inguinal hernias. PMID- 1863311 TI - Statistical analysis of visual analog scales. PMID- 1863312 TI - Vibrio vulnificus sepsis presenting as leg pain and lower extremity rash. PMID- 1863314 TI - Difficulties in identifying Klebsiella strains of clinical origin. AB - Two hundred and four strains of Gram-negative bacteria of clinical origin, initially identified as Klebsiella using the API 20 E system, and 10 reference strains were further analysed with the API 20 EC test system and the API 50 CH, API 50 AO, API 50 AA assimilation systems. Four clusters corresponding to the species Klebsiella pneumoniae subsp. pneumoniae, K. oxytoca, K. planticola, and K. terrigena were formed after numerical analysis of 155 selected tests and the 26 most discriminating tests were determined. A comparison was made between conventional identification using the API 20 E system and the results of the numerical analysis. The conventional method resulted in incorrect identification of 13% of the strains tested, especially for the new species: K. planticola and K. terrigena. After numerical analysis, 17 out of 204 strains (8.3%) of clinical origin were identified as K. planticola. Only 1 strain of clinical origin was identified as K. terrigena, and 1 strain as K. ornithinolytica. PMID- 1863313 TI - [Where can I open my office? Demographic study of the dental profession in Spain]. PMID- 1863315 TI - Menaquinone patterns of Amycolatopsis species. AB - The menaquinones of representative strains of the actinomycete genus Amycolatopsis were examined by reverse phase thin-layer chromatography and mass spectrometry. Representatives of all seven validly described species contained various combinations of di-, tetra- and hexahydrogenated menaquinones with nine isoprene units as predominant isoprenologues. It seems likely that the variation in the predominant menaquinones merely reflects the stages from the growth cycle from which biomass was taken. The detection of major proportions of hydrogenated menaquinones with nine isoprene units serves to distinguish Amycolatopsis strains from most other actinomycetes, notably those belonging to related genera such as Amycolata and Pseudonocardia. PMID- 1863316 TI - Legiolysin, a new hemolysin from L. pneumophila. AB - Legionella pneumophila generates exotoxins, cytolysins, proteases or hemolysins that damage host cells like erythrocytes or tissue culture cells. The gene for a new L. pneumophila hemolysin without a proteolytic activity was identified, cloned in E. coli and sequenced. The gene product was analysed by SDS Polyacrylamide-gel-electrophoresis. PMID- 1863317 TI - Application of impediometry to rapid assessment of liquid culture media. AB - The impedance method provides as unique opportunity to determine microbial activity and kinetics. Since the metabolic processes depend on the nature and quality of the culture medium, impediometry allows the assessment of liquid culture media. Impedance microbiology represents an approach to quantitative microbiology. We investigated the influence of pH, composition and variation of the amounts of industrially made dry media, overheating during the dissolving or sterilisation processes, and qualitative differences between batches of the same culture medium. Using glucose broth as an example, we showed that impediometry allows quantitative, microbial assessment of culture media. Inaccurate preparation of the culture medium could be detected quickly by the use of impediometry. The method is very simple to perform, requires no sample preparation, allows rapid assessment of liquid culture media, and interprets results automatically with the aid of a microcomputer. PMID- 1863318 TI - Clinical and genetic aspects of Shiga-like toxin production in traditional enteropathogenic Escherichia coli. AB - Cell culture tests, DNA colony blot hybridization and polymerase chain reaction were used to examine classical enteropathogenic Escherichia coli (EPEC) for the presence of Shiga-like toxin (SLT). Fifteen of 155 strains from West Germany, originally identified as EPEC on the basis of serotyping, were shown to harbor either SLT-I or SLT-II genes. All strains that hybridized with the 20-base oligonucleotide probes which are complementary to slt-IA or slt-IIA sequences derived from the genomic DNA of enterohemorrhagic E. coli O157:H7 strain 933 produced moderate or high levels of cytotoxin in Vero and HeLa cell assays. Four additional strains of low to moderate cytotoxicity did not hybridize with either probe. Five different serogroups producing SLTs were identified: O26, O55, O111, O119 and O128. All three SLT-positive E. coli O26:H11 and four of five E. coli O111:H- isolates hybridized with a 3.4 kilobase fragment (CVD 419 probe) derived from the 60-megadalton plasmid of EHEC O157:H7. Seven of the 15 SLT-gene positive strains were associated with bloody diarrhea, six isolates were from patients with hemolytic uremic syndrome (HUS). Based on their clinical, epidemiological, pathogenic and genetic features SLT-producing E. coli among classical EPEC mimic enterohemorrhagic E. coli O157:H7 and might be considered as EHEC. PMID- 1863319 TI - The mature MgPa-adhesin of Mycoplasma genitalium. AB - A high molecular weight protein of Mycoplasma genitalium (MgPa-protein) was isolated by fractionated solubilization with 1% CHAPS, followed by subsequent extraction with 2% octylglucoside and size exclusion chromatography. The comparison of the N-terminal sequence reported here with published nucleotide sequence data revealed the existence of a signal sequence; the molecular weight of the mature MgPa-protein was calculated to be 153, 134 dalton. The protein shares antigenic determinants with the adhesin of Mycoplasma pneumoniae (P1 protein). Therefore the amino acid sequence of the MgPa-protein was matched to the P1-protein sequence. Five of seven computer predicted hydrophobic regions of both amino acid sequences were located in corresponding regions. PMID- 1863320 TI - Interaction of Cryptosporidium parvum and Campylobacter jejuni in experimentally infected neonatal mice. AB - By the method of scanning electron microscopy (SEM), the inner mucosal surface of the ileum, ceacum and colon was studied in inbred BALB/c mice. Two-day-old mice were infected with either 10(6) oocysts of Cryptosporidium parvum and 10(8) CFU of porcine and human strains of the bacterium Campylobacter jejuni or with a combination of both enteropathogens. Pathological changes in infection with C. parvum were related to enterocytes and villous atrophy appeared. In infection with C. jejuni, pathological changes were related to goblet cells. In combined infections, pathological changes were similar to those in monoinfections and occurred simultaneously within the intestine. Synergistic interaction of C. parvum and C. jejuni manifested itself morphologically in a more intense colonization of the inner surface of the small and large intestine by C. jejuni, in a more intense infection of the caecum and colon by C. parvum, and in prolongation of severe, massive infection of the small and large intestine, and also a prolongation of the patent period. PMID- 1863321 TI - Follicle and oocyte growth in early postnatal calves: cytochemical, autoradiographical and electron microscopical studies. AB - The initiation of oocyte and follicle growth was studied in 1- and 3-d-old calf ovaries using cytochemical, autoradiographical and electron microscopical approaches. Attention was only paid to unilaminar ovarian follicles that were classified into 3 categories: unilaminar flattened (UF), unilaminar flatto cuboidal (UFC) and unilaminar cuboidal (UC) ovarian follicles when the oocyte was surrounded by 1 layer of flattened, a mixture of flattened and cuboidal and entirely cuboidal follicle cells, respectively. Our findings suggested that oocytes within each of these follicle categories were in different developmental stages. Furthermore, electron microscopic observations revealed that early after birth, oocyte nuclei characteristic of diplotene configuration (aggregation of the nuclear chromatin into moderately electron-dense small patches and fibrillo granular texture of the nucleolus) were encountered in 41% of the UF follicles. The rest of the UF as well as all of the UFC and UC follicles were found to contain dictyate oocytes in which the chromatin was highly decondensed and the nucleolus differentiated into fibrillar, fibrillo-granular and granular components. The present results also indicated that the complete transition of the surrounding follicle cells from flattened to cuboidal shape and the morphological changes of the oocyte endoplasmic reticulum and mitochondria were 2 complementary events essential for initiation of oocyte growth. PMID- 1863323 TI - In vitro fertilization in cattle: a review. AB - In vitro maturation and fertilization of cattle oocytes and subsequent in vitro culture of zygotes and embryos is discussed in the context of recent encouraging data. Mass production of embryos produced in this way in the future will have a great impact on animal production and animal breeding plans, for example the so called MO-ET (multiple ovulation and embryo transfer) plan which aims at establishing nucleus breeding herds. PMID- 1863322 TI - Somatic cells and the G2 to M-phase transition in sheep oocytes. AB - New protein synthesis is essential in sheep oocytes for the progression of the meiotic cycle to metaphase. Inhibition of transcription by alpha-amanitin, a specific inhibitor of RNA polymerase II, arrests meiosis in the G2 phase in cumulus enclosed oocytes but denuded oocytes progress to M-phase. Denuded oocytes injected with alpha-amanitin also undergo maturation. Cumulus-enclosed and denuded oocytes were also cultured on transcriptionally inactive follicle shells to examine the influence of transcription in the granulosa cell compartment on the progression of meiosis. No effect of alpha-amanitin was detected on the maturation rate of both cumulus enclosed and denuded oocytes. We conclude that transcription is required in the cumulus cells to allow translation of stored messages within the oocytes coding for cell-cycle proteins. PMID- 1863325 TI - A stereotaxic atlas and implantation technique for nuclei of the diencephalon of Atlantic salmon (Salmo salar) parr. AB - A stereotaxic apparatus and technique for its implantation in diencephalic nuclei of Atlantic salmon parr of 20 to 30 g body weight is described. An atlas of nuclei in the diencephalon is also presented. PMID- 1863324 TI - The effect of endotoxin-contaminated medium on in vitro fertilization and development of bovine oocytes matured in vitro. AB - The purpose of this study was to determine whether the presence of bacterial endotoxin in the bovine serum albumin (BSA) used to supplement media utilized for sperm preparation and co-culture of bovine sperm and oocytes affects in vitro penetration and embryonic development of oocytes matured in vitro. The chromogenic limulus amoebocyte lysate (LAL) test was used for quantification of the content of endotoxin. The proportion of penetrated ova was significantly greater (P greater than 0.0005) for the endotoxin-contaminated group (89%) versus the non-contaminated group (61%), but this was probably not due to endotoxin contamination. The presence of endotoxin resulted in a high rate of polyspermy (27% versus 4%, respectively; P greater than 0.0005), while the occurrence of parthenogenetic activation was the same for each group (8%). The proportion of total embryos put into culture that developed to the blastocyst stage by day 8 was similar (30% and 26%) for the contaminated and non-contaminated group, respectively. Fifty-three and 69%, respectively, hatched on day 10. These results suggest that endotoxin induces polyspermy, but has no adverse effect on embryonic development. PMID- 1863326 TI - [A theoretical study on the biological origins of Chinese herbs]. AB - Ten new theoretical points concerning the biological origins of Chinese herbs are presented in this paper, i.e. continuity of the biological origins of Chinese herbs, mutation of the biological origins of Chinese herbs; optimum seeking theory of rising species of medicinal herbs; mono-original and limit d multi original Chinese herbs; etc. PMID- 1863327 TI - [Textual and herbal studies on shashen and qini (Adenophora spp.)]. AB - This paper reports the origins of the Chinese traditional drugs nanshashen and beishashen, as well as the original plants of shashen, xingyeshashen, xiyeshasen and qini recorded in the bencaological works of the past dynasties. Our study shows that shashen is Adenophora stricta, both xingyeshashen and qini are A. hunanensis and xiyeshashen is A. paniculata. PMID- 1863328 TI - [Medicinal Polygonatum in northwest China]. AB - This paper reports 16 species of medicinal plants of Polygonatum found in northwest China, along with their distribution, ecological conditions, infraspecies variations and clinical applications. A key to the species is provided. PMID- 1863329 TI - [Quality of Schisandra incarnata Stapf]. AB - In the western part of Hubei province we have collected a medicinal plant by the local name of "North Wuweizi". It has been identified as Schisandra incarnata. A tetrahydrofuran lignan chicanine has been isolated from the kernel of the plant. Pharmacological experiments show that S. incarnata possesses activities of lowering sGPT levels as well as prolonging the sleeping time induced by phenobarbital. PMID- 1863330 TI - [Preliminary infection source of downy mildew of Corydalis yanhusuo W. T. Wang]. AB - The downy mildew of Corydalis yanhusuo caused by Peronospora corydalis usually brings about devastating harm in Anhui Province. In the past, it was generally held that the spores in diseased remains buried in soil were the main source of preliminary infection. But, according to our test, it is the mycelia in tubers that are mainly the preliminary infections source. PMID- 1863331 TI - [A preliminary survey on the growing tempo of Chinemys reevesii (Gray)]. AB - The growing tempo of tortoises is closely related with the temperature and intake of food. In suitable temperature range (20-28 degrees C), the intake increases with the rise of temperature and the growth accordingly accelerates. In the dormant period, the tortoise consumes more energy as ambient temperature rises. PMID- 1863332 TI - [Quantitative determination of sugars in radix Aconiti and its processed products by two kinds of colorimetry]. AB - Sugar contents in Radix Aconiti and its processed products were determined by phenol-H2SO4 method and chromotropic acid-H2SO4 method, and found to decrease in various degrees during processing. The results given by the two methods are similar. PMID- 1863333 TI - [Determination and study of inorganic elements in liuwei dihuang decoction by ICP AES]. PMID- 1863334 TI - [Chemical constituents of Alyxia levinei Merr]. AB - Three compounds were isolated from the stem and leaves of Alyxia levinei. On the basis of spectrometric analysis and physico-chemical constants they were identified as oleanolic acid, betulin and beta-sitosterol-D-glucoside respectively. PMID- 1863335 TI - [A preliminary research on the quality of musk]. AB - In this paper liquid crystal b-PBPeB was adopted as the GC-stationary liquid phase. From the ether extract of musk, androsterone, muscone and cholesterol were identified. Comparative analysis of 13 samples of musk has proved this method to be useful in the quality evaluation of musk. PMID- 1863336 TI - [Determination of glycyrrhetinic acid in radix Glycyrrhizae by TLC densitometry]. AB - A TLC densitometric method for the determination of glycyrrhetinic acid in Radix Glycyrrhizae is described. The method is accurate, sensitive and simple. The recovery of glycyrrhetinic acid is 98.30% and the coefficient of variation of five samplings is 2.20%. PMID- 1863337 TI - [Anti-oxidation of Paecilomyces Sinensis (S. Pnov.)]. AB - This paper indicates that Paecilomyces sinensis ig 3g/kg/dx14 increases the amount of superoxide dismutase in the liver tissues of mice; that Paecilomyces sinensis is similar to natural Cordyceps sinensis in inhibiting the production of Lpo and increasing the amount of superoxide dismutase in the liver homogenates of mice in vitro. In addition Paecilomyces sinensis can also increase the amount of glutathione peroxidase in the liver homogenates of mice in vitro. PMID- 1863338 TI - [Anti-tumor effect of Cetraria laevigata Rassad. polysaccharides]. AB - The anti-tumor effect of Cetraria laevigata polysaccharides has been investigated in mice using sarcoma 180; Ehrlich ascitic tumor, cervical carcinoma u-14 and leukemia L7217. The results show that Cetraria laevigata polysaccharides may inhibit the growth of sarcoma 180, Ehrlich ascitic tumor and cervical carcinoma u 14 in mice at a dose of 200mg/kg ip (1/5 LD50). However, the survival time of leukemia L7217 wasn't prolonged. The reticuloendothelial system phagocytic function in mice was increased at ip doses of 50 mg/kg and 100 mg/kg (1/10 and 1/20 LD50). PMID- 1863339 TI - [Advances in the research on Apoacynum]. PMID- 1863340 TI - Formulation and validation of a degree in health care. PMID- 1863341 TI - Leg lengthening in children--current techniques and radiology. PMID- 1863342 TI - Industry re-shaping of diagnostic imaging--the next decade. PMID- 1863343 TI - The use of stents in bronchial compression. PMID- 1863344 TI - A psychological case study into the needs and problems experienced by an in patient receiving radiotherapy. PMID- 1863345 TI - Computerised tomography: its role in the assessment of ear disease. AB - A retrospective study was undertaken of 205 patients who had been referred for CT scanning of the middle ear and the cerebello-pontine angle. Data from the case notes and radiographs were used to assess the accuracy of high resolution CT in the diagnosis of cholesteatoma and acoustic neuroma, the two diseases which provide the bulk of our work load from the ENT department. The risk factors, including the dose and use of contrast agents, and the cost and time of the examinations has also been considered. An assessment of radiation dose to the eye lens was made for each procedure to indicate the risk to benefit ratio for each radiographic examination. This investigation showed that high resolution CT can accurately diagnose ear disease, while providing an efficient use of resources at low risk to the patient. Positive and negative predictive values of one were obtained for acoustic neuroma; cholesteatomas produced positive and negative predictive values of 0.83 and 0.66 respectively. Plain radiography and polytomography gave information about the bone anatomy of the ear but did not demonstrate the soft tissue component of the disease, so that a negative result from either of these procedures did not exclude a lesion but a positive result was not informative enough to permit surgery. PMID- 1863346 TI - Scattered radiation and the lumbar spine. PMID- 1863347 TI - Immunological tolerance and lymphokines. PMID- 1863348 TI - The various faces of right upper lobe atelectasis. AB - The most common cause of RUL atelectasis in adults is neoplasm obstructing the RUL bronchus. Scarring of the lobe following chronic infection comes next. Other causes of obstruction, whether central or peripheral, are less common. The only direct sign of atelectasis is approximation of the fissures. All other signs are indirect. Increased density of the collapsed lobe is the most noticeable indirect sign. In the absence of adhesions the RUL is fixed at the hilum only. Therefore, it may take any one of the different shapes. Usually it is not difficult to recognize the dense shrunken lobe. Otherwise, we will have to depend on the other indirect signs, namely, displacement of mediastinal structures, elevation of the right hemidiaphragm, juxtaphrenic peak, elevation of hilum, "disappearance" of RUL artery, changes in position of of vascular (and bronchial) markings, and displacement of granuloma (if present). PMID- 1863349 TI - Comparison of MRI and CT for study of renal and perirenal masses. AB - Accurate preoperative assessment of renal and perirenal tumors is crucial in determining the type of therapy and/or in planning the operative approach. Computed tomography has been used extensively to stage renal cancer by defining the extent of disease within and outside the kidney, demonstrating patency of the renal vein and inferior vena cava, and depicting sites of lymph node involvement. Recent studies have shown magnetic resonance imaging to be comparable or superior to computed tomography in staging renal carcinoma. Because of its multiplanar imaging capabilities, MRI has also proven useful in evaluating perirenal masses that may obstruct, displace, or invade the kidney. The advantages and limitations of MRI and CT are discussed and their current roles in the evaluation of renal and perirenal abnormalities are reviewed. PMID- 1863350 TI - Morphological and functional characterization of a hormonally induced AIMS/GRXII cell line. AB - The AIMS/GRXII cell line is a product of the line of research our laboratory is pursuing to understand the response of target cells to sustained hormonal stimulation, a situation simulating the one that brings about in vivo tumorigenesis. The cell line was derived from goat ovarian granulosa cells subjected to luteinizing hormone stress (high doses repeated). It was found to be contact-inhibited, nontumorigenic and secreted progesterone. The majority of cells at any given passage showed hypodiploidy. The cell line required hormonal support till passage 8 after which it was hormone-independent. Thus, the system offers a phase-wise development of the cell line which might be useful in cancer research, particularly to understand the mechanisms of cell transformation at the cellular and molecular level and possible hormone (onco)gene nexus in cell proliferation. PMID- 1863351 TI - Sensitivity of desquamin to proteolytic degradation. AB - The stratum corneum is both a desquamating and degradative tissue; cell contacts become weaker in the outer lamellae and a variety of proteolytic and glycolytic enzymes cleave many macromolecules into free amino acids and saccharides. We have reported on a 40-kilodalton glycoprotein from human stratum corneum; because of its unique lectin-like properties, we believe that it plays a major role in desquamation and have named it desquamin. If desquamin is to function as a lectin during desquamation, it must survive enzymatic degradation in the outer stratum corneum. Accordingly, we treated this glycoprotein with a number of proteinases and found that desquamin is resistant in vitro to most of the types of proteinases that have been reported in the stratum corneum as well as several others that have not been identified as present in the tissue. In the stratum corneum, the lipids of the intercorneal mortar shield the glycoproteins; hence, desquamin is even less likely to be susceptible to endogenous proteolysis in vivo than in vitro. PMID- 1863352 TI - Enumeration of antigen sites on cells by flow cytometry. AB - We evaluated a cytofluorometric method for determining the number of antigens expressed on the cell surface of human lymphocytes. Using beads that have a known number of binding sites for mouse immunoglobulin and monoclonal antibodies specific for various antigens on human lymphocytes, we found that this system is quite reproducible, reliable and technically easy to perform. The greatest source of variation in expression of cell surface antigens is interdonor variability. PMID- 1863353 TI - Inhibition of chemically induced neoplastic transformation in vitro by saturated fatty acids. AB - Syrian hamster embryo cells were treated for 2-4 days with 3-methylcholanthrene (MCA), and 28 days after application of the carcinogen they were exposed continuously to 12-O-tetradecanoylphorbol-13-acetate (TPA). Untreated cells, or cells treated with MCA or TPA only, usually became senescent around 6-8 weeks after plating and died, but those treated with both MCA and TPA became immortalised and underwent transformation to a phenotype capable of growth in soft agar. Transformation was inhibited by derivatives of stearic acid administered to the cells at various stages of the overall process. Some derivatives were active at lower concentrations than others, but none were selective for specific phases such as initiation or promotion, and it did not appear to matter whether the fatty acids were present throughout the assay or for only part of it. Their action seems to be associated with control of growth or differentiation in a relatively non-specific manner. PMID- 1863354 TI - Characterization of human esophageal carcinoma cell line established on confluent monolayer, and advantage of confluent monolayer surface structure for attachment and growth. AB - Biopsy tissue from a 72-year-old Japanese woman with metastasis to the cervical lymph nodes of recurrent esophageal carcinoma was adapted for culturing on the surface of lethally X-irradiated confluent monolayers of Balb/c 3T3 cells, and a continuous-growing tumor cell line was developed. These cells were found to contain keratinous material by immunohistochemical staining. We confirmed that these cells were of human origin by performing chromosome analysis. Thus, this line, designated as KSE-2 line, was considered to have originated from metastatic squamous-cell carcinoma of the human esophagus. When the attachment and growth of KSE-2 was examined on various culture surfaces, the confluent monolayers of Balb/c 3T3 cells were found to be more suitable than other substrata, such as plastic and collagen-coated dishes. The fixation of confluent monolayers of 3T3 cells with 3% glutaraldehyde had almost no affect on the colony-forming efficiency of the KSE-2 cells. In addition, the period of lag phase after inoculation of KSE-2 cells on fixed as well as nonfixed monolayers was shorter than that on plastic dishes. The conditioned medium from lethally X-irradiated 3T3 cells did not enhance the attachment and proliferation of KSE-2 cells on both nonfixed and fixed confluent monolayers. From these results, the surface structure itself of the 3T3 confluent monolayer was considered to play an important role in the favorable attachment and proliferation of KSE-2 cells. PMID- 1863355 TI - Effects of low-density lipoprotein from normal rabbits on hypercholesterolemia and the development of atherosclerosis. AB - To clarify whether or not normal LDL separated from normal rabbits is atherogenic, 0.75 mg of normal LDL-cholesterol in 6 ml of 0.85% saline and 6 ml of saline alone were injected every day for 5 weeks into the auricular vein of two groups of rabbits, respectively. The inoculated rabbits were fed a standard diet containing 0.5 and 1% cholesterol. Blood was drawn before injection and at 1, 2, 3 and 5 week intervals thereafter. After 5 weeks, all rabbits were sacrificed. Following exsanguination, the aorta was stained by Sudan III. The Sudan III staining was more extensive in rabbits injected with saline than in those that received LDL. In addition, plasma cholesterol, plasma phospholipid, VLDL-cholesterol and LDL-cholesterol levels were lower in LDL-injected rabbits than in those injected with saline. But HDL-cholesterol levels were not significantly different between LDL-cholesterol and saline-injected rabbits. Although the exact cause of antiatherogenic effect of normal LDL is not clear, it seems reasonable to suggest that at least some normal LDL acts as a 'good' lipoprotein, namely antiatherogenic lipoprotein, in our experimental protocol. PMID- 1863356 TI - Reappraisal of the role of macrophages in the pathogenesis of atherosclerosis. AB - New Zealand rabbits were fed an atherogenic diet, 8 with and 8 without twice weekly intravenous injections of GdCl2. The injections caused a reduction in the phagocytic activity of the reticuloendothelial system by one fourth to one half. No significant differences were found between the two groups in the planimetric extent of atheromata in the aortae. GdCl2 treatment inhibited the deposition of sudanophilic lipids in depth of the arterial wall. The findings indicate that macrophages are the primary foam cells and their uptake of lipoproteins is essential for the deposition of lipids in myocytes. Lipid-laden myocytes and ground substance mucopolysaccharides represent sinks in which lipids are removed from the flow and accumulate locally. PMID- 1863357 TI - Comparative analysis of sequences at the 5' end of the human and mouse apolipoprotein B genes. AB - A comparison was made between the DNA sequences in two regions of the mouse and the human apolipoprotein B genes: the 5'-flanking sequence and the region between the first exon and the second intron. Considerable homology was observed, particularly in the immediate 5' region and in the second intron. Because promoter and enhancer elements have been previously localized to these regions in the human apolipoprotein B gene, it is proposed that regions of conserved base sequence delineate binding regions for regulatory proteins. In some cases, contiguous regions of homology are longer than expected for regions designed as recognition sites for individual nuclear proteins, and may define regions recognizable by a cluster of interacting proteins. Both the human and mouse genes contain repetitive elements and a hypervariable dinucleotide repeat. PMID- 1863358 TI - Expression and regulation of adrenodoxin and P450scc mRNA in rodent tissues. AB - The rate-limiting step in steroidogenesis is the conversion of cholesterol to pregnenolone. This reaction occurs in steroidogenic tissue in the inner mitochondrial membrane, and is mediated by the cholesterol side-chain cleavage enzyme. This enzyme system transfers electrons from NADPH to cholesterol through its three protein components: adrenodoxin reductase, adrenodoxin, and the terminal oxidase, P450scc. We have previously shown that P450scc mRNA is regulated by tropic hormones and cAMP by a cycloheximide-independent mechanism in mouse Leydig tumor MA-10 cells. We now show that the mRNA for adrenodoxin, another component of the cholesterol side-chain cleavage enzyme system, is regulated by tropic hormones and cAMP in MA-10 cells. We cloned rat adrenodoxin cDNA to analyze adrenodoxin mRNA in various rat tissues and in MA-10 cells by RNase protection assays. Adrenodoxin mRNA is found in virtually all rat tissues examined, although it is most abundant in adrenals, ovaries, and testes. MA-10 cells synthesize two species of adrenodoxin mRNA, one of 1.2 kb and the other of 0.8 kb. Both of these adrenodoxin mRNAs are increased approximately six-fold by 1 mM 8-Br-cAMP, five-fold by 10 microM forskolin, and three-fold by both 25 ng/ml hCG and by 100 ng/ml LH. Maximal adrenodoxin mRNA accumulation occurs by 4 h of hormonal stimulation. The cAMP-mediated increase in adrenodoxin mRNA accumulation is independent of protein synthesis, since treatment with cycloheximide or puromycin in the absence or presence of cAMP does not inhibit, and even increases, adrenodoxin mRNA accumulation. PMID- 1863359 TI - Regional mapping of genes encoding human steroidogenic enzymes: P450scc to 15q23 q24, adrenodoxin to 11q22; adrenodoxin reductase to 17q24-q25; and P450c17 to 10q24-q25. AB - Steroid hormones are synthesized by a complex array of 10 enzymes. The genes for each of these have now been cloned, and previous work has determined the regional chromosomal assignments of six of these. We used in situ hybridization to determine the regional chromosomal assignments of the four remaining enzymes. The CYP11A1 gene encodes mitochondrial P450scc, which converts cholesterol to pregnenolone, and is located on 15q23-q24. The gene for adrenodoxin, which receives electrons from adrenodoxin reductase and transfers them to P450scc, is on 11q22 while its pseudogenes are on 20q11-q12. The gene for adrenodoxin reductase is on 17q24-q25. The CYP17 gene encodes P450c17, which has both 17 alpha-hydroxylase and 17,20-lyase activities, and is located on 10q24-q25. None of the 10 genes involved in human steroidogenesis is closely linked to another gene for a steroidogenic enzyme. PMID- 1863360 TI - Fimbria-fornix transections disrupt the ontogeny of delayed alternation but not position discrimination in the rat. AB - In Experiment 1, Long-Evans rat pups received fimbria-fornix transections or sham surgery on Postnatal Day 10 (PND10) and were then trained on PND23 to perform either a discrete-trials delayed alternation (DA) or a simple position discrimination (PD) task in a T maze. Rat pups in both surgical conditions learned the PD task within five 12-trial blocks of training. However, only sham operated pups learned the DA task. In Experiment 2, performance of DA emerged between PND19 and PND27 in sham-operated pups but failed entirely to develop in pups with early lesions. In Experiment 3, fornix-transected pups that were given extended DA training (132 trials) on PND23-PND24 showed some improvement in performance but remained impaired in relation to sham-operated controls. These findings implicate the limbic system in the postnatal development of DA but not PD and suggest that dual-process theories of memory may be relevant to the psychobiology of cognitive development. PMID- 1863361 TI - Classical conditioning after temporal lobe lesions in man: impairment in conditional discrimination. AB - Left and right temporal lobectomy patients, patients with frontal lobe lesions, and healthy control subjects participated in an eyelid conditioning study based on conditional discrimination learning. All groups acquired the first conditioned response at a similar time during learning, but both temporal lobectomy groups showed poorer discrimination than control subjects. The results support models that relate hippocampal function to operation of if-then rules. PMID- 1863362 TI - Slow-wave activity in the spectral analysis of the electroencephalogram is associated with cortical dysfunctions in patients with Alzheimer's disease. AB - Cortical functions and slow-wave activity in the spectral analysis of the electroencephalogram (EEG) have been studied in 19 patients with Alzheimer's disease (AD), 18 patients with Parkinson's disease with dementia (PD), and 14 control subjects (C) to determine which functions are explained by their relationship of slow-wave activity. Multiple regression analyses revealed that a variance in visual functions, praxia of the hand, automatic speech, speech understanding, and retrieval from semantic memory were explained by their relationship with slow-wave activity in EEG in the AD group but not in the PD or C groups. The PD and AD groups exhibited equal cortical dysfunctions and mean amplitudes of delta activity in EEG. The cholinergic system, disrupted in AD, has been shown to be important in the regulation of neocortical electrical activity and may be associated with the processing of cortical functions. PMID- 1863363 TI - Habituation produces frequency-specific plasticity of receptive fields in the auditory cortex. AB - Associative learning produces conditioned stimulus (CS)-specific plasticity of frequency receptive fields (RFs) in the auditory cortex; responses to the CS frequency are increased, whereas responses to other frequencies are decreased. This study determined the effects of habituation on the RF of neurons in the auditory cortex of the guinea pig (Cavia porcellus). One frequency was presented repeatedly (REP) followed by redetermination of the RF. After REP, 26/36 (72%) RFs exhibited a substantial reduction (70-75%) of response to the repeated frequency, and this was highly specific (bandwidth less than 0.125 octave). This RF plasticity involves an initial decrease in response during REP but does not require attenuated responses at the end of REP. Incubation (i.e., development over time after cessation of REP) and long-term frequency-specific effects are evident. Thus, habituation induces a specific change in the processing of frequency information rather than a general reduction in responsivity. PMID- 1863364 TI - Opioid modulation of pavlovian learning in rabbits: involvement of sublenticular pathways. AB - Intravenous naloxone enhanced, and D-Ala2-Met-enkephalinamide (DALA) impaired, Pavlovian conditioned heart rate discrimination in rabbits (Oryctolagus cuniculus) during initial training trials, compared with saline; naloxone also delayed subsequent extinction of the discrimination. These effects of the opioid treatments on discrimination were abolished by parasagittal knife-cut lesions in the sublenticular substantia innominata that did not, themselves, impair discrimination. Both naloxone and DALA decreased the magnitude and altered the topography of bradycardiac conditioned responses, and the lesions also abolished these effects of the opioid treatments, but they did not alter the effect of naloxone to decrease bradycardiac orienting response magnitude. These findings suggest that fibers in the sublenticular area mediate specifically the effects of systemic opioids on associative functions during Pavlovian cardiac conditioning and extinction. PMID- 1863365 TI - Posttraining D1 receptor blockade impairs odor conditioning in neonatal rats. AB - Rat pups that were exposed to a novel anise odor paired with tactile stimulation (stroking the skin with a paint brush) received injections of either saline or the dopamine D1 receptor antagonist (+/-)-SKF 83566 (0.1 mg/kg) before conditioning or immediately after conditioning. Animals that received the drug either before or after training showed less approach to the conditioned odor during the testing period 24 hr later than did animals that received the vehicle. Posttraining administration of the D2 receptor antagonist spiperone (0.1 mg/kg) did not affect subsequent approach to the conditioned odor, suggesting a selective effect of D1 receptor blockade. The impairment in learning by the administration of (+/-)-SKF 83566 before conditioning was reversed by the injection of the dopamine receptor agonist apomorphine (0.1 mg/kg) immediately after conditioning. Posttraining D1 receptor activation appears necessary for normal odor conditioning in rat pups. PMID- 1863366 TI - Visuospatial asymmetries and interocular transfer in the split-brain rat. AB - Interocular transfer (IOT), hemispheric superiority, and cerebral dominance were examined in split-brain female albino rats. Callosum-sectioned and intact animals were monocularly trained in the Morris water maze and tested in IOT and reversal phases. In the IOT phase, split-brain rats entered more nontarget quadrants and headed less accurately toward the platform than did controls. For both split brain animals and controls, right-eye training resulted in shorter latencies and fewer nontarget entries than did left-eye training. Analyses of cerebral dominance showed shorter latencies and smaller heading errors over all 3 phases in rats that were trained with the nondominant eye. Right-eye dominant controls were less affected by platform reversal. Split-brain rats were inferior to controls in latency to find the platform and in target quadrant entries. This finding establishes a spatial cognitive deficit from callosum section. PMID- 1863367 TI - Oxytocin selectively increases holding and licking of neonates in preweanling but not postweanling juvenile rats. AB - Preweanling rats exhibit components of maternal behavior (MB) after brief periods of contact with neonates; the latency of onset of MB rises considerably after weaning. Oxytocin (OXT) stimulates MB in adult rats. The effects of intracisternal (IC) administration of OXT (2 micrograms) on pup-directed and other behaviors in preweanling and postweanling juvenile rats were tested. Compared with saline and no treatment, OXT significantly increased active holding of pups in preweanling but not postweanling juvenile rats. No other components of adultlike MB were stimulated by OXT. OXT also decreased inactive touching of pups and robustly increased selfgrooming in juveniles at all ages tested. It is concluded that OXT facilitation of active pup-holding and licking in preweanling rats may be an extension of OXT-induced self-grooming to pups and may also be related to OXT activation of MB in adult rats. PMID- 1863368 TI - Conditioned changes in pain reactivity: II. In search of the elusive phenomenon of conditioned hyperalgesia. AB - Previous research suggests that a stimulus that has been paired with an aversive event can elicit either an increase (hyperalgesia) or decrease (hypoalgesia) in pain reactivity in rats. Attempts have recently been made to isolate the variables that determine the direction of the conditioned response. Very little evidence has been found for conditioned hyperalgesia when a spinally mediated measure of pain reactivity (the tail-flick test) was used. In the present study, the impact of a conditioned stimulus was assessed using a procedure modeled after one in which conditioned hyperalgesia was obtained with the tail-flick test (Davis & Hendersen, 1985, Experiment 4). With this training paradigm, a discrete conditioned stimulus was found to elicit hypoalgesia but not hyperalgesia. PMID- 1863369 TI - Radial maze learning deficits and mediodorsal thalamic damage in context of multifocal seizure-induced brain lesions. AB - Rats were either trained 21 days after seizure induction or trained before seizure induction and tested 21 days later. The seizures, which induce insidious brain damage within a multitude of diencephalic and subcortical telencephalic structures, were induced by a single injection of lithium (3 mEq/kg sc) followed 24 hr later by pilocarpine (30 mg/kg sc). Compared with controls, the treated rats displayed significant deficits in the acquisition and recall of a radial maze task. Although there was multifocal brain damage, only the amount of damage within the mediodorsal thalamic group was significantly and strongly correlated (rho = .79) with numbers of errors. PMID- 1863370 TI - Light-dark differences in behavioral sensitivity to oxytocin. AB - Ovariectomized female rats treated with estradiol benzoate (EB) and progesterone (P) were infused intracerebroventricularly with a low (200 ng) or high (1 microgram) dose of oxytocin (OT). The low dose of OT facilitated lordosis behavior only during the dark phase of the light-dark cycle in females that were pretreated with low doses of EB (2 micrograms) and P (250 micrograms). In contrast, the high dose of OT facilitated lordosis behavior during both the light and the dark phases but only in long-term ovariectomized females that were primed with large amounts of EB (2 x 10 micrograms) and P (500 micrograms). In females that were primed with lower amounts of ovarian steroids, the high dose of OT failed to increase levels of lordosis responding in either the dark or light phase. Thus, when female rats are treated with physiological amounts of ovarian hormones and OT, they are more sensitive to the facilitative effects of the OT on lordosis behavior during the dark phase. PMID- 1863371 TI - Multiple cerebral abscesses. PMID- 1863372 TI - The initial experience with the Cosman-Roberts-Wells stereotactic system. AB - The Cosman-Roberts-Wells stereotactic instrument is a recently developed modification, based on an arc-radius design, of the Brown-Roberts-Wells stereotactic frame utilizing the existing fixation and fiducial components of the Brown-Roberts-Wells stereotactic system to localize and verify target data. The design modification has been made with a view to facilitating technical approaches both in stereotactic biopsy and in stereotactic craniotomy, whilst encompassing the same stereotactic space. Initial experience with the Cosman Roberts-Wells instrument is reported. Over a 5-month period 55 procedures were performed which included 40 stereotactic biopsies, five CT-guided stereotactic craniotomies, three stereotactic placements of a Bennett Ball for thalamotomy, three stereotactic implantations of intracranial electrodes for recording in drug resistant epilepsy, three aspirations of cyst or haematoma and one implantation of a Gutin catheter for interstitial brachytherapy. There was minimal morbidity and no mortality related to operation. This frame offers rapid targeting without the need to pre-determine entry points, as well as allowing direct lateral passes and unimpeded stereotactic craniotomy. PMID- 1863373 TI - Results of follow-up after removal of non-functioning pituitary adenomas by transcranial surgery. AB - The records of 53 patients who had undergone transcranial surgery for a non functioning pituitary adenoma were reviewed. The most common symptom in these patients was visual loss (51 patients). Headache was the presenting symptom in 25 and hypopituitarism in 18. After surgery 17 of the patients were symptom free, 26 were improved, while seven remained unchanged. Three patients died. Other complications occurred in 12 patients but without serious long-term morbidity. Radiation therapy was given to patients in whom subtotal resection of tumour was achieved. None of these patients had tumour recurrence in a mean follow-up period of 76 months, while of the patients in whom tumour extirpation seemed to be complete, 36% had tumour recurrence. PMID- 1863374 TI - Is a skull X-ray necessary after milder head trauma? AB - During the 2-year period 1985-86 a total of 1,876 patients were admitted to our hospital after milder head trauma including cerebral concussion. Two hundred and eighty four patients who had a skull X-ray were not selected from guidelines. In 1,592 patients without a skull X-ray, signs of an intracranial complication developed in six cases and were verified by CT. In the 284 patients with skull X ray a fracture was demonstrated in 25, and of these 25 patients only one patient disclosed a cerebral contusion. In the 259 patients with skull X-ray, but without demonstration of fracture, there were subsequently seen one subdural haematoma and one cerebral contusion. The incidence of intracranial complications in patients without and with skull X-ray with or without fracture does not differ significantly. In these circumstances we do not find any justification for routine skull X-ray after milder head trauma. PMID- 1863375 TI - Hindbrain migration after decompression for hindbrain hernia: a quantitative assessment using MRI. AB - Pre- and post-operative assessments are presented in 17 adult patients who have been treated with craniovertebral decompression for hindbrain herniation, 11 of whom had syringomyelia. Objective improvement in the size of the syrinx was seen in all 11 cases; contrary to expectation the hindbrain more frequently moved downwards than upwards after decompression of the tonsils and creation of an artificial cisterna magna. A method is reported for the quantitative assessment of hindbrain migration using magnetic resonance imaging (MRI). The degree of 'slump', further downward displacement of the hindbrain, was compared with the clinical outcome and the MRI appearances. Slump was more common than expected, although the severity was not usually great enough to produce symptoms. Slump was less marked where the artificial cisterna magna was generous (p less than 0.02). This quantitative method may be useful in assessing patients with unexplained post-operative symptoms and in comparing different surgical techniques. PMID- 1863377 TI - Intraoperative ultrasound-guided biopsy of intracranial lesions: comparison with freehand biopsy. AB - Achieving the required accuracy during such relatively straightforward procedures as tumour biopsy or abscess aspiration remains a challenge especially for the more junior neurosurgeon. A study comparing freehand biopsy with ultrasound guided biopsy is presented. The use of intraoperative ultrasound increases the accuracy at the expense of a slightly longer operating time. Diagnostic tissue was always obtained using this technique. PMID- 1863376 TI - Multiple brain abscess: a review of fourteen cases. AB - The case notes of 14 consecutive patients with multiple brain abscesses presenting over a 14 year period were studied with respect to the incidence and presentation, the source of infection, the investigations, microbiology and the treatment and outcome. The incidence of multiple brain abscesses in non immunocompromised patients is 13% of all intracranial abscesses. Computerized tomographic scanning is vital both in the detection of multiple abscesses and in the subsequent assessment of therapy. The source of infection in half of our patients was the teeth or the paranasal sinuses. Streptococci were isolated in 63% of the patients; staphylococci in 21%. This has obvious implications for the antibiotic policy. Intracranial surgery, with few exceptions, had a diagnostic and management role rather than a curative one; identification of the causative organism was its prime purpose. CSF, obtained by lumbar punctures, did not provide any positive cultures and should not be contemplated in view of the inherent hazards. The elimination of the primary focus of infection was a most important step in the management of this condition. Multiple brain abscesses represent a potentially curable condition, provided appropriate antibiotics are used, the primary septic focus is eliminated and the intracranial complications are anticipated by the use of frequently repeated CT scans. PMID- 1863378 TI - The value of intraoperative ultrasound in neurosurgery. AB - Intraoperative ultrasound is not a technique which has been widely accepted by neurosurgeons in this country, not least because bulky probes and machines become more of a hindrance than an asset in theatre. The development of new smaller probes, including ones small enough to visualize the brain through a conventional burr-hole has rekindled interest in this subject. Its use for guidance in tumour biopsy, cyst aspiration and catheter placement, as well as volume estimations and determining the completeness of tumour resection, are outlined. The ability to recognize peri-operative haemorrhage is demonstrated. PMID- 1863379 TI - Access to anteriorly placed tumours in the posterior fossa by medullotomy. AB - Access to tumours lying in front of the brain stem may be restricted by the neuraxis and cranial nerves, the tentorium, and the bony configuration of the skull base. When there is distortion and attenuation of the brain stem, direct access through the medulla should be considered. A case is described. PMID- 1863380 TI - The blasted pheasant. PMID- 1863381 TI - Subarachnoid haemorrhage in Wegener's granulomatosis, with negative four vessel angiography. AB - Two patients with Wegener's granulomatosis and spontaneous subarachnoid haemorrhage are presented in whom four vessel angiograms were normal. The diagnosis of Wegener's granulomatosis should be considered in patients with subarachnoid haemorrhage and negative four vessel angiography. The presence of antibodies to a neutrophil cytoplasmic antigen may be of diagnostic value. PMID- 1863382 TI - Spontaneous trigemino-pontine pneumocephalus. AB - A case of a spontaneous trigemino-pontine pneumocephalus in a 25-year-old man without any known risk factors is described. Other cases of spontaneous pneumocephalus in the literature are briefly reviewed. PMID- 1863383 TI - Intracranial malposition of nasogastric tube following transnasal transsphenoidal operation. PMID- 1863384 TI - Osteogenesis imperfecta and basilar impression. PMID- 1863385 TI - Skill development in vigilance: effects of event rate and age. AB - Thirty-six young (19-27 years), middle-aged (40-55 years), and old (70-80 years) adults performed a 30-min vigilance task at low (15 per min) and high (40 per min) event rates for 20 sessions. Skill-acquisition curves modeled on power, hyperbolic, and exponential functions were predicted. With extensive practice, hit rates increased and false-alarm rates decreased to virtually asymptotic levels. Skill development was best described by the hyperbolic function. Practice reduced but did not eliminate the vigilance decrement in all subjects. The event rate effect--the decrease in hit rate at high event rates--was reduced with practice and eliminated in young subjects. Hit rates decreased and false-alarm rates increased with age, but there was little attenuation of age differences with practice. Implications for theories of vigilance, skill development, and cognitive aging are discussed. PMID- 1863386 TI - Financial strain and psychological well-being among the American and Japanese elderly. AB - Research in the United States indicates that stressful life events may create psychological distress among older adults by eroding their sense of personal control and by diminishing their feelings of self-worth. The purpose of this study was twofold: (a) to replicate these findings with data provided by a recent nationwide survey of elderly people in the United States (N = 1,523) and (b) to compare these findings with results obtained from a nationwide survey of older adults in Japan (N = 1,517). The findings from both surveys are quite similar. The data indicate that financial strain tends to erode feelings of control and self-worth in both cultures, and the weakening of these personal resources in turn tends to increase depressive symptoms. PMID- 1863387 TI - Grandmothers' advice about disciplining grandchildren: is it accepted by mothers, and does its rejection influence grandmothers' subsequent guidance? AB - To test whether maternal grandmothers' advice affects mothers' punishing of their children and whether mothers' disciplinary actions influence subsequent suggestions by these grandmothers, 40 three-generational families were examined. After receiving advice purportedly from the grandmothers, mothers rewarded and punished their 10-year-olds' successes and errors on a task. Participants were in separate rooms so that simulated information about the grandmothers' advice, mothers' disciplinary decisions, and children's performances could be systematically manipulated under controlled conditions. The grandmothers' sham "suggestions" to mothers about punishing appeared either to begin leniently but progressively intensify or to start harshly but gradually mollify. Information to grandmothers about the mothers' "punishing" likewise either became increasingly severe or indulgent. All children, however, appeared to continue performing uniformly. Mothers generally modified their disciplining to correspond to the grandmothers' apparent advice, and grandmothers' actual suggestions conformed toward the mothers' simulated discipline. Grandmothers appear to be one of many influences affecting mothers' decisions about their children. PMID- 1863388 TI - Social support, stress, and depressive symptoms among the elderly: test of a process model. AB - Effects of social support, negative life events, and daily hassles on depressive symptoms were assessed in 301 adults aged 65 or older, in person 3 times at 6 month intervals and by mail questionnaires every month over a 12-month period. Initial social support predicted severity of depressive symptoms 12 months later. Social support and initial levels of depressive symptomatology predicted number of daily hassles but not number of major life events. Effects of social support, depression, and major life events on the incidence of daily hassles remained significant without the inclusion of hassles reflecting depressive symptomatology or problems in relationships or whose content overlapped with major life events. Daily hassles mediated the effects of major life events on subsequent depression. Results did not differ for men and women. Implications for models of the relations among social support, stress, and depression are discussed. PMID- 1863389 TI - Relation of work and retirement to health and well-being in older age. AB - Patterns of labor-force participation were studied with a broad array of indicators of physical and psychological well-being. The sheer amount of work- whether people work and, if so, how many hours they work--shows little relationship to health and well-being. Drawing on scattered existing research and theory, it is hypothesized and found that persons whose patterns of labor-force participation (or nonparticipation) reflect their personal preference report higher levels of physical and psychological well-being than do those whose level of labor-force involvement is constrained by other factors. The results do not differ by gender, age (65 years and older vs. 55-64 years), or occupation (professional vs. clerical or sales vs. blue-collar workers). Data are from 1,339 respondents 55 years of age or older in the Americans' Changing Lives Survey, a large national, cross-sectional survey of Americans 25 years of age and older with an oversample of those 60 years of age and older, and are analyzed by ordinary least squares multiple regression. PMID- 1863390 TI - Changes in depressive-symptom experiences among older women. AB - Changes in depressive-symptom experiences over a 5-year period were investigated in a community sample of 251 women between the ages of 51 and 92 years. Findings from a confirmatory factor analysis of the SCL-90-R Depression and Additional Symptoms scales (Derogatis, 1983) indicate that two phenomenally different syndromes underlie symptom-reporting patterns. A depressive syndrome, more classic in form, shows decreasing levels with increasing age, although a depletion syndrome, marked by feelings of enervation and a loss of interest in things, shows increasing levels with advancing age. The relative independence of the two syndromes, as well as their differing relations to four more delimited forms of distress that were identified in the analyses, have important implications for future research on the age-depression relation. PMID- 1863391 TI - Differential social support and life change as contributors to the social class distress relationship in older adults. AB - Four hypotheses previously put forth to explain the strong association between social class and mental health in the general population were examined in 1,326 older adults (55 years and older). Respondents were interviewed 3 times at 6 month intervals. Lower class was associated with more past life changes (occurring before Wave 1) and more subsequent life events (occurring between Waves 1 and 3); these changes were predictive of distress, supporting the differential exposure hypothesis. Lower class was associated with weaker social support (embeddedness), which was related to distress, supporting the resource deterrent hypothesis. There was little evidence that people of the lower classes were more vulnerable to stress or that their status was due to their weaker social support; thus, the differential vulnerability and applied buffering hypotheses were not consistently supported. Social support does appear to be a versatile resource for older adults. A significant portion of the class-distress relationship was not accounted for by life change, social support, or the interaction between these factors. PMID- 1863393 TI - Dependence in the elderly from an interactional point of view: verbal and observational data. AB - Dependence in the elderly was investigated from an interactional point of view. Observations as well as verbal data of the elderly and professional caregivers were considered. Samples consisted of 14 elderly people receiving regular home health care (M = 78.9, SD = 6.3 years) and 16 elderly people receiving regular nursing home care (M = 81.4, SD = 7.5 years). Results showed a strong tendency toward independence in the elderly. Sense of control in the self-care interactions observed was higher in the home health care group than in the group receiving nursing home care. Division of the elderly into subgroups with high, medium, and low perceived self-efficacy showed that the elderly high in self efficacy were more independent in terms of observed self-care. Causal explanations of the elderly's competence and their nonuse of competence were significantly different between the elderly and staff. PMID- 1863392 TI - Dimensions of perceived social support in clinically depressed and nondepressed female caregivers. AB - The relationship between social support and depression was studied in 165 women caring for frail family members. The Arizona Social Support Interview Schedule (Barrera, Sandler, & Ramsay, 1981), which includes 4 dimensions of availability and use of resources and satisfaction with and need for support, was used to examine 7 categories of supportive activity. Depression was assessed according to Research Diagnostic Criteria (Spitzer, Endicott, & Robins, 1978) with the Schedule of Affective Disorders and Schizophrenia (Endicott & Spitzer, 1978). There were no differences in overall satisfaction with received support in comparisons of depressed and nondepressed caregivers. However, depressed caregivers (n = 87) reported a higher incidence of negative interactions with others. Both groups appeared to have equal access to social support, with nondepressed caregivers (n = 78) reporting significantly greater use of those resources. PMID- 1863394 TI - Age and depression: unique and shared effects. AB - The degree to which psychosocial variables associated with depression were also associated with age was examined in 3 samples of community residents 50 years of age or older (N = 4,617). Most of the expected concomitants of depression were found. With only a few exceptions, age was not correlated with depression-related psychosocial variables. Rather, age was most strongly associated with levels in neuropsychological and psychophysiological functioning. In addition, the magnitudes of the correlations in women compared with men and in young-old age groups compared with old-age groups were examined. A number of significant differences emerged, and their implications for theories of depression are noted. PMID- 1863395 TI - Adult age differences in letter-level and word-level processing. AB - Older and young adults' letter detection and lexical decision performance were examined as word frequency varied to determine whether there were age differences in word recognition. Allen and Madden (1989) found that older adults' pattern of reaction time (RT) across word frequency categories was different from young adults' pattern for a letter detection task. In this study, for both letter detection and lexical decision tasks, older adults exhibited a monotonically decreasing RT function as word frequency increased. However, young adults exhibited a nonmonotonic RT function across word frequency for the letter detection task but a monotonically decreasing RT function as word frequency increased for the lexical decision task. An expanded parallel input serial analysis model of word processing was hypothesized. PMID- 1863396 TI - What types of reminiscence are associated with successful aging? AB - To resolve the controversy regarding the adaptive benefits of reminiscence, the study was conducted to investigate what types of reminiscence are associated with successful aging. On the basis of prior research and content analysis, 6 types of reminiscence were identified: integrative, instrumental, transmissive, narrative, escapist, and obsessive. Successful aging was operationally defined as higher than average ratings in mental and physical health and adjustment as determined by an interviewer and a panel of gerontological professionals. Reminiscence data were gathered from 88 men and women judged to be aging successfully and 83 men and women judged to be aging unsuccessfully. All subjects were between 65 and 95 years of age, with approximately half living in the community and half in institutions. As predicted, successful agers showed significantly more integrative and instrumental reminiscence but less obsessive reminiscence than their unsuccessful counterparts. Community dwellers also showed more instrumental and integrative reminiscence than institutionalized seniors showed. Thus, only certain types of reminiscence are beneficial. PMID- 1863398 TI - Possible selves in adulthood and old age: a tale of shifting horizons. AB - Young, middle-aged, and elderly adults (N = 308) evaluated themselves on 6 dimensions of psychological well-being according to present, past, future, and ideal self-assessments. Young and middle-aged adults saw considerable improvement in themselves from the past to the present on all dimensions of well-being. The elderly, however, indicated largely a perception of stability with prior levels of functioning. Future ratings showed that the 2 younger groups expected continued gains in the years ahead, whereas the oldest respondents foresaw decline on most aspects of well-being. The comparison of present and ideal self ratings supported (cross-sectionally) the hypothesis that with age, individuals achieve a closer fit between their ideal and their actual self-perceptions. PMID- 1863397 TI - Assessment of depression in patients with Alzheimer's disease: concordance among informants. AB - This study is an investigation of the concordance among different sources of information on ratings of depression in patients with Alzheimer's disease (AD). Informants were 75 outpatients with diagnosed AD (22 with major depressive disorder), their caregivers, and geriatric clinicians. Clinicians rated each patient on the Hamilton Rating Scale for Depression on the basis of (a) the patient's report, (b) the caregiver's report, and (c) the clinician's evaluation. Overall, patients perceived themselves as less depressed than did caregivers or clinicians; for nondepressed patients, caregivers reported patients less depressed than clinicians reported; for depressed patients, no significant differences were obtained between caregiver or clinician. Certain items were more discrepant among informants and significantly differentiated depressed from nondepressed AD patients. Level of patient dementia did not affect ratings. These findings support the need for comprehensive, accurate assessment of depression in AD patients. PMID- 1863399 TI - Aspects of written language production over adult life. AB - Self-descriptions written by adults were analyzed to explore the effects of age, gender, vocabulary, nonverbal intelligence, and educational-occupational status on lexical aspects of language and grammatical complexity. Multivariate analyses indicated that, after controlling for other background variables, age had a significant effect on vocabulary diversity, sentence complexity, subordinating conjunctions, and possibly sentence length. Four variables--word output, word length, long words, and readability--were affected mainly by vocabulary and educational-occupational status. An unexpected and small but significant gender difference in the readability of the descriptions was observed across all age groups. PMID- 1863400 TI - Spatial memory in young and elderly adults: category structure of stimulus sets. AB - In 1987, Sharps and Gollin reported that the spatial memory of older adults is aided more than that of young adults by visually distinctive cues to location. In 1990, Park, Cherry, Smith, and Lafronza failed to reproduce these results. In the present study, strong category structure yielded results analogous to those of Park et al., and weak category structure similar to that of Sharps and Gollin yielded the same pattern of results as those in their study. The categorical interrelatedness of stimulus items was shown to be of potential importance in the resolution of the discrepancy between the 2 reports. PMID- 1863401 TI - Zidovudine therapy is associated with an increased capacity of phytohemagglutinin stimulated cells to express interleukin-2 receptors. Pittsburgh AIDS Clinical Trial Unit. AB - Zidovudine therapy of AIDS patients has been shown to cause only transient improvements in the numbers of circulating CD4+ cells and the in vitro functional activities of cultured lymphocytes. The present studies were undertaken to determine whether prolonged zidovudine therapy enhanced reactivity in two sensitive assays of T-cell function: the ability of phytohemagglutinin (PHA) stimulated cells to form T-cell colonies and their capacity to express receptors for the growth factor interleukin-2 (IL-2). Treated patients, studied over periods of 20-60 weeks, showed no improvement in colony formation at any time interval, even in plates supplemented with exogenous IL-2. However, mitogen stimulated T lymphocytes showed a significant increase in the capacity to express IL-2 receptors (CD25). This enhanced expression resulted primarily from activation of the CD8+ cell subset. PMID- 1863402 TI - Absence of a clinical correlation for complement-mediated, infection-enhancing antibodies in plasma or sera from HIV-1-infected individuals. Multicenter AIDS Cohort Study Group. AB - Neutralizing and complement-mediated infection-enhancing antibodies to HIV-1 were measured in sera or plasma from 54 HIV-1-positive individuals at various stages of disease, and from an additional 36 HIV-1-positive individuals for whom no clinical data were available. Antibodies were measured in microtiter infection assays utilizing MT-2 cells and the IIIB strain of HIV-1. The frequency of detection of both types of antibodies was identical, being 77 out of 90 cases (86%). Neutralizing and infection-enhancing antibodies were not always found together, and in four cases both were undetectable. No correlation was found between titers of either type of antibody and stage of disease. Furthermore, titers of infection-enhancing antibodies at early stages of disease did not predict rate of disease progression. PMID- 1863404 TI - Cellular profiles in bronchoalveolar lavage fluid of HIV-infected patients with pulmonary symptoms: relation to diagnosis and prognosis. AB - Bronchoalveolar lavage (BAL) cell differentials and T-lymphocyte subpopulations were analysed in 95 HIV-infected patients with pulmonary symptoms to determine whether the type of cellular inflammatory response could be useful in diagnosis or as a prognostic marker. Patients with Pneumocystis carinii pneumonia (PCP) had more BAL fluid lymphocytes, mainly comprising CD8+ cells, and patients with bacterial infection had more neutrophils than other patients. Neither of these changes were mirrored in peripheral blood. Seven patients who died after their acute episode of PCP had significantly higher BAL fluid neutrophils than 53 patients with PCP who survived (P = 0.002). There seems to be correlation between BAL fluid neutrophilia, PCP and concomitant bacterial infection since four out of seven patients with a fatal outcome had coinfection with bacteria, whereas only one patient with PCP and bacterial coinfection survived (P = 0.0007). PMID- 1863403 TI - The prevalence of oral lesions in HIV-infected homosexual and bisexual men: three San Francisco epidemiological cohorts. AB - To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposi's sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CI) 17.5-23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% CI 4.1-7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposi's sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P less than 0.05). The prevalence of erythematous candidiasis and Kaposi's sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status. PMID- 1863405 TI - Expression of major histocompatibility complex and HIV antigens within the brains of AIDS patients. AB - HIV establishes a chronic infection in the central nervous system (CNS) of AIDS patients. The immunopathogenesis of this chronic encephalitis is unknown. Because of the importance of major histocompatibility (MHC) class I and class II antigens in modulating the immune response, we examined the tissue expression of MHC molecules in relation to CNS damage and expression of viral antigens. By immunocytochemical staining we found that beta 2-microglobulin (beta 2M) expression is elevated in all cases with signs of viral encephalitis. beta 2M was expressed at high levels on endothelial cells, macrophages and possible oligodendroglia within regions of histopathology. In histologically normal regions elevated expression of beta 2M was noted only on endothelial cells. MHC class II expression was elevated only in the HIV encephalitis cases, and was restricted to macrophages/microglia and occasional endothelial cells. When compared with other viral encephalitides these findings suggest that the intra CNS immune response to HIV is appropriate for viral presentation; however, the absence of responsive systemic T cells may lead to chronic viral infection. PMID- 1863406 TI - Prevalence of HIV, hepatitis B and associated risk behaviours in clients of a needle-exchange in central London. AB - In order to determine the prevalence of risk behaviour for, and antibodies to HIV and hepatitis B in clients of a needle-exchange scheme in central London we employed an anonymous, self-administered questionnaire along with salivary antibody testing by immunoglobulin (Ig) G antibody capture immunoassay. Two hundred and thirty-two subjects (193 men, 39 women; median age 32) participated; a response rate of 89%. Clients were long-term, frequent injectors. Lending used equipment at any time was reported by 55%, and borrowing by 52%. Of those who had shared needles and syringes during the last year, the majority had lent to, or borrowed from, one person only (53 and 55%, respectively). Younger clients (less than 29 years of age) reported more recent sharing than older clients (greater than 30 years of age). Five out of 211 (2.4%) samples tested for anti-HIV were positive. One hundred and eleven out of 199 (56%) samples were positive for anti hepatitis B core (HBc). In this population of needle-exchange attenders there is no evidence of further spread of HIV, and a low prevalence of HIV infection appears to have been sustained. However, the high prevalence of anti-HBc provides evidence of previous risk behaviour and so constant vigilance is necessary if further viral spread is to be avoided. This study has established an acceptable method for the anonymous surveillance of current risk behaviour and salivary antibodies to HIV and hepatitis B virus (HBV) in a drug-using population. PMID- 1863407 TI - Evaluation by women consulting in a family planning centre of their risk of HIV infection. AB - In order to assess women's self-perception of their risk of infection by HIV, research was performed among 654 women who had consulted in a family planning centre in the Paris region. Of the 452 (69%) women who took part in this research, 77% considered themselves as 'not at risk of carrying the AIDS virus', 11% as 'at risk' and 12% did not give a specific answer. The most important risk factors noted by the patient and the doctor were found to be the number of partners, the use of syringes and the non- or faulty use of condoms. Estimates of the risk of infection by physicians had a high correlation with those of the women, although there were wide differences between the opinions of the six doctors involved. In one case out of three the doctors were unable to decide whether or not their patient was at risk. The evident difficulties experienced by these physicians show an urgent need for the development of specific medical training programmes. The seroprevalence of 2.4% of HIV infection among the women studied, and 1.1% of those who consulted during the study period, confirm the importance of carrying out specific studies on women consulting in family planning centres. PMID- 1863408 TI - Cerebrospinal fluid and serum neopterin and biopterin in D-retrovirus-infected rhesus macaques (Macaca mulatta): relationship to clinical and viral status. AB - Increases in serum and cerebrospinal fluid (CSF) neopterin concentrations accompany many inflammatory diseases, including infection with HIV-1 and may reflect activation of guanosine triphosphate (GTP) cyclohydrolase 1 by gamma interferon and other cytokines. In the present study, macaques with clinical simian AIDS (SAIDS) infected with the immunosuppressive type-D retrovirus D/1/California had increased concentrations of CSF neopterin but not of biopterin beginning soon after seroconversion. Normal neopterin concentrations in the CSF were found in macaques with SAIDS-related complex as well as asymptomatic, viremic macaques. CSF biopterin, serum neopterin and serum biopterin concentrations of D/1/California-infected macaques were not different from the levels in control animals. The increase in CSF neopterin may reflect local inflammatory responses and paralleled previously documented changes in L tryptophan metabolism in these macaques. However, the absence of macrophage infiltrates in the brain of the infected macaques suggests a non-macrophage source of both increased CSF neopterin and tryptophan metabolites in the SAIDS macaques. PMID- 1863409 TI - Testing of saliva for antibodies to HIV-1. AB - To determine whether saliva is a potentially useful sample for screening for HIV infection when serum is not obtainable, saliva and serum samples from 50 HIV infected and 50 uninfected subjects were tested for antibody to HIV-1 (anti-HIV 1) using a second-generation enzyme-linked immunosorbent assay (ELISA; Abbott) and prototype antibody-capture ELISA (Wellcome). Of saliva specimens from HIV infected people, six gave negative results on the Abbott and one on the Wellcome assays; all specimens from uninfected people were negative by both assays. Sensitivity for the Abbott assay was therefore 88.0% [95% confidence interval (Cl) 76.2-94.4%], an unacceptable level for screening purposes. Sensitivity for the Wellcome assay was 98% (95% Cl 89.5-99.6%), a more satisfactory level for population screening. Further validation of this technique is necessary, and of methods for collection of saliva specimens in particular. PMID- 1863410 TI - Selection of primers of optimal sensitivity for the detection of HIV-1 from Africa and Europe by polymerase chain reaction. AB - In order to facilitate the detection of integrated HIV-1 proviral DNA from African as well as European patients, four new primer pairs for use in the polymerase chain reaction (PCR), localised in the gag, pol, vif and env genes of HIV-1, were constructed. The primer pairs were compared to all accessible HIV-1 sequences from African and European isolates and to some of the earlier published and most commonly used primer pairs. HIV-1 DNA was detected in blood drawn from 13 out of 13 individuals infected in Africa, in three out of three Tanzanian HIV 1 isolates and in three out of three asymptomatic Swedes infected in Europe. The new selection of primer pairs can be used as an alternative to enhance the detection of HIV-1 of different origins. PMID- 1863411 TI - Risk factors for HIV among prostitutes in Chiangmai, Thailand. AB - The discovery of a 44% (44 out of 100) prevalence rate of HIV infection among female prostitutes working in brothels in Chiangmai in Thailand in June 1989, prompted this follow-up study in August to confirm the high prevalence rate and to look for risk factors for infection. We studied 238 female prostitutes working in 14 brothels and confirmed this high prevalence rate. Eighty-seven (36.5%) out of 238 prostitutes were found to be HIV-positive by enzyme-linked immunosorbent assay with IFA or Western blot confirmation. Logistic regressions found a significant association between HIV infection and frequency of sexual intercourse greater than 3 times per day [odds ratio (OR) = 2.82, 95% confidence interval (CI) = 1.47-5.41], sexual service charge less than 150 Baht (OR = 9.1, 95% CI = 2.9-33.3), and post sexual cleansing with water alone (OR = 3.85, 95% CI = 1.90 7.80). Of 56 women found seronegative in the June survey, 35 were re-tested in the August study. Seven (20%) of them were seropositive, giving an HIV seroconversion incidence rate of 10% per month. The findings of this study prompted intensive health education programmes among prostitutes, their customers, and owners of brothels. PMID- 1863412 TI - Sulfadiazine-induced crystalluria in AIDS patients with toxoplasma encephalitis. AB - Toxoplasma encephalitis is the most common opportunistic infection of the central nervous system in patients with AIDS. The treatment of choice is a combination of sulfadiazine and pyrimethamine. We present here four patients with AIDS treated for toxoplasmic encephalitis who developed sulfadiazine-induced crystalluria. This complication was rapidly reversible with rehydration and urine alkalinization. Patients with AIDS treated with high doses of sulfadiazine should be adequately hydrated, and their urinary pH maintained above 7.5 to prevent sulfadiazine-induced crystalluria. PMID- 1863413 TI - Syphilis treatment response in HIV-infected individuals. AB - The adequacy of treatment for syphilis has routinely been evaluated by the serological response, i.e. the rapid plasma reagin test (RPR). Since the description of AIDS and HIV aspects of both the natural history of syphilis and the response of Treponema pallidum to treatment have come under increased scrutiny. With concurrent epidemics of HIV and syphilis in New York City, a serological case-control study was done to determine whether HIV-infected individuals given treatment for primary or secondary syphilis have a modified serological response. All study participants had primary or secondary syphilis and paired specimens available for testing. Cases were defined as people who were HIV-positive and were compared with controls who were HIV-negative. HIV-infected patients with primary syphilis when compared with HIV-negative controls were less likely to have a fourfold or greater RPR decrease or seroreversion within 6 months of treatment [15 out of 28 versus 153 out of 210; odds ratio = 0.4, P less than 0.05]. Cases and controls with secondary syphilis had similar serological responses after treatment for syphilis. Although this study adds to the growing body of literature which suggests that HIV may alter the RPR response, prospective studies are needed to determine definitively whether HIV alters the serological response to therapy in patients with early syphilis. PMID- 1863414 TI - Effects of prostaglandin E2 on replication of HIV-1 in human peripheral blood mononuclear cells. PMID- 1863416 TI - Zidovudine treatment increases erythrocyte adenosine deaminase activity. PMID- 1863415 TI - Twice-weekly dapsone-pyrimethamine for preventing PCP and cerebral toxoplasmosis. PMID- 1863417 TI - Invasive external otitis caused by Aspergillus fumigatus in two patients with AIDS. PMID- 1863418 TI - Intestinal microsporidiosis due to Enterocytozoon bieneusi: a new case report in an AIDS patient. PMID- 1863419 TI - Radiosensitivity of HIV-1--potential application to sterilization of bone allografts. PMID- 1863420 TI - Neurological manifestations of HIV-1 infection. PMID- 1863421 TI - Structure of 1% copper(II)-doped dichlorobis(1,2-dimethylimidazole)zinc(II). AB - [Zn0.99Cu0.01Cl2(C5H8N2)2], Mr = 328.43, monoclinic, P2(1)/c, a = 13.587 (1), b = 7.1324 (7), c = 16.356 (2) A, beta = 112.87 (1) degrees, V = 1460.4 (5) A3, Z = 4, Dm = 1.50 (1), Dx = 1.492 g cm-3, mu(Mo K alpha, lambda = 0.71073 A) = 20.8 cm 1, F(000) = 672.0, T = 297 (1) K, R = 0.028 for 1782 unique observed reflections. The structure contains discrete dichlorobis(1,2-dimethylimidazole)zinc(II) molecules. Pseudotetrahedral N2Cl2 coordination about zinc is effected by coordination to two imidazole and two chloride ligands. The Zn-N [2.006 (3), 2.008 (3) A] and Zn-Cl [2.2509 (8), 2.2468 (8) A] distances lie within +/- 0.01 A of those in the structurally similar compound [ZnCl2(imidazole)2]. Angles within the coordination sphere L-Zn-L' range from 105.39 (7) to 115.37 (8) degrees. The N-Zn-N angle [115.37 (8) degrees] is 5-10 degrees larger than those for several [ZnL2Cl2] complexes where L is imidazole, 4-substituted pyridine or 3,5 dimethylpyrazole. PMID- 1863422 TI - Structures of two conformationally defined phenylethanolamines: exo-1,4-epoxy-2 formamido-1,2,3,4-tetrahydro-8-trifluoromethylnaphthale ne and exo-1,4-epoxy-2 formamido-1,2,3,4-tetrahydro-6-trifluoromethylnaphthale ne. AB - (+/-)-exo-1,4-Epoxy-2-formamido-1,2,3,4-tetrahydro-8- trifluoromethylnaphthalene (1), C12H10F3NO2, Mr = 257.21, Pccn, a = 8.895 (1), b = 19.968 (5), c = 12.656 (3) A, V = 2247.9 (8) A3, Z = 8, Dx = 1.520 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 1.49 cm-1, F(000) = 1056, T = 297 K, R = 0.0466 for 1481 independent reflections collected. The torsion angle for N(10)-C(2)-C(1)-C(8a) is 167.4 (2) degrees. (+/-)-exo-1,4-Epoxy-2-formamido-1,2,3,4-tetrahydro-6- trifluoromethylnaphthalene, (2), C12H10F3NO2, Mr = 257.21, P2(1)2(1)2(1), a = 8.52 (2), b = 26.15 (2), c = 5.06 (5) A, V = 1127 (11) A3, Z = 4, Dx = 1.516 g cm 3, lambda(Mo K alpha) = 0.71069 A, mu = 1.29 cm-1, F(000) = 528, T = 297 K, R = 0.108 for 932 independent reflections collected. The torsion angle N(10)-C(2) C(1)-C(8a) is 172.5 (6) degrees; the formamido group in both (1) and (2) is exo. X-ray studies on (1) suggest a hydrogen bond between N(10) and O(12) and similarly for (2). PMID- 1863423 TI - Absolute configurations of three ent-beyerene derivatives. AB - (1): 11 beta,17-Bis(4-bromobenzoyloxy)-9 beta-hydroxy-ent-beyerene, C34H38Br2O5, Mr = 686.5, orthorhombic, P2(1)2(1)2(1), a = 6.1686 (12), b = 14.613 (3), c = 32.935 (7) A, V = 2969 (1) A3, Z = 4, Dx = 1.536 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 27.43 cm-1, F(000) = 1408, T = 173 K, R = 0.0347 and wR = 0.0358 for 3064 reflections [Io greater than or equal to 3 sigma(Io)]. (2): 7 beta,17 Bis(4-bromobenzoyloxy)-9 beta-hydroxy-ent-beyerene, C34H38Br2O5, Mr = 686.5, monoclinic, P2(1), a = 12.6424 (15), b = 6.8353 (12), c = 18.496 (2) A, beta = 101.901 (9) degrees, V = 1564.0 (4) A3, Z = 2, D chi = 1.458 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 26.03 cm-1, F(000) = 704, T = 173 A, R = 0.0336 and wR = 0.0361 for 4610 reflections [Io greater than or equal to 3 sigma(Io)]. (3): 17-(4 Bromobenzoyloxy)-9 beta,11 beta-epoxy-7 beta-hydroxy-ent-beyerene, C27H33BrO4, Mr = 501.5, orthorhombic, P2(1)2(1)2(1), a = 6.1315 (7), b = 18.389 (3), c = 21.109 (3) A, V = 2380.0 (6) A3, Z = 4, D chi = 1.399 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 17.38 cm-1, F(000) = 1048, T = 198 K, R = 0.0325 and wR = 0.0344 for 2292 reflections [Io greater than or equal to 3 sigma(Io)].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863424 TI - Structure of two polymorphs of 2-methyl-3,4'-bipyridin-6(1H)-one. AB - C11H10N2O, Mr = 186.22. Polymorph (I) monoclinic, P2(1)/c, a = 7.574 (1), b = 11.132 (2), c = 11.437 (2) A, beta = 94.90 (1) degree, V = 960.8 (5) A3, Z = 4, Dx = 1.287 Mg m-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.079 mm-1, F(000) = 392, T = 293 K, R = 0.058 for 2335 observed reflections. Polymorph (II) monoclinic, P2(1)/c, a = 6.7897 (7), b = 13.449 (2), c = 10.736 (1) A, beta = 108.644 (8) degrees, V = 928.9 (2) A3, Z = 4, Dx = 1.331 Mg m-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.082 mm-1, F(000) = 392, T = 293 K, R = 0.047 for 1952 observed reflections. The molecular conformations in the two polymorphs are similar and the torsion angle C(2)--C(1)--C(1')--C(2') is 58.9 (2) and 54.1 (2) degrees for (I) and (II), respectively. Both structures contain centrosymmetric hydrogen bonded dimers of molecules with the pyridone ring NH groups acting as donors and the keto O atoms as acceptors with N...O distances of 2.776 (2) and 2.765 (1) A for (I) and (II), respectively. PMID- 1863425 TI - Huperzine A--a potent acetylcholinesterase inhibitor of use in the treatment of Alzheimer's disease. AB - Huperzine A, 9-amino-13-ethylidene-11-methyl-4-azatricyclo [7.3.1.0(3,8)]trideca 3(8),6,11-trien-5-one, C15H18N2O, Mr = 242.32, monoclinic, P2(1)/n, a = 8.8574 (6), b = 12.1833 (7), c = 12.4278 (7) A, beta = 99.956 (5) degrees, V = 1320.9 (1) A3, Z = 4, Dx = 1.22 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 5.75 cm-1, F(000) = 520, T = 296 K, RF = 6.30% for 1402 reflections with Fo greater than or equal to 5 sigma(Fo) and 183 parameters. The pyridone ring is planar and the stereochemistry of the C(11)--C(12) double bond is E. PMID- 1863426 TI - Structure of (+/-)-aminoglutethimide. AB - (+/-)-3-(4-Aminophenyl)-3-ethyl-2,6-piperidinedione, C13H16N2O2, Mr = 232.3, monoclinic, P2(1)/n, a = 16.895 (2), b = 8.519 (1), c = 8.762 (1) A, beta = 95.71 (1) degree, V = 1254.9 (2) A3, Z = 4, Dx = 1.23 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.785 cm-1, F(000) = 496, T = 294 K, R = 0.064 for all 3676 reflections. The molecule is L shaped with the p-aminophenyl and the piperidinedione groups forming the vertical arm and the base, respectively. The polar imide half of the piperidinedione group is in front of the L for the active + enantiomer and at the back for the less-active - enantiomer. The structure is very similar to that of phenobarbital. Intermolecular interactions include one strong and one weak hydrogen bond and an apparent interaction between one of the amino H atoms with the pi cloud of the phenyl ring. PMID- 1863427 TI - Structure of aqua-hexakis(mu 2-benzoato)-bis(methanol)-mu 3-oxo-triiron(III) benzoate ethanol methanol solvate. AB - [Fe3(O)(C7H5O2)6(CH3OH)2(H2O)]-[C7H5O2]-C2H5OH-CH3OH (1/1/1), Mr = 1191.56, triclinic, P1-, a = 11.591 (3), b = 13.308 (2), c = 20.154 (3) A, alpha = 96.910 (12), beta = 96.95 (2), gamma = 114.10 (2) degrees, V = 2767.1 (9) A3, Z = 2, Dx = 1.43 g cm-3, mu = 8.471 cm-1, Mo K alpha radiation, lambda = 0.7107 A, F(000) = 1234, T = 198 K, R = 0.0522 for 6252 reflections [Fo greater than or equal to 4 sigma (Fo)]. The complex has nearly D3h symmetry with two coordinated CH3OH molecules and one coordinated H2O molecule. The coordination around the Fe atoms is essentially octahedral. Each Fe atom lies slightly out of the plane of the O atoms of the bridging benzoates and is directed towards the mu 3-O atom. The average Fe--O distances are 1.907 (2) A for the mu 3-O atom and 2.010 (1) A for the benzoate O atoms. PMID- 1863428 TI - Structure of a key intermediate in the asymmetric synthesis of (+)-KDO. AB - Methyl 3-deoxy-7,8-O-(1-methylethylidene)- 1-O-(phenylmethyl)-alpha-D-manno-2 octalopyranoside cyclic carbonate, (1), C20H26O8, Mr = 394.42, orthorhombic, P2(1)2(1)2(1), a = 10.667 (3), b = 10.7972 (14), c = 16.509 (5) A, V = 1901.4 (8) A3, Z = 4, Dx = 1.38 g cm-3, mu = 0.9960 cm-1, lambda(Mo K alpha) = 0.7107 A, F(000) = 840, T = 298 K, R = 0.0355 for 2248 reflections, Fo greater than or equal to 4[sigma (Fo)]. The X-ray structure was undertaken to confirm the stereochemistry of the substituents on the six-membered pyranose ring. The two rings are cis-fused with ring junction torsion angles of -18.7 (3) degrees for C2 C3-C8-C9 and -18.2 (2) degrees for O4-C3-C8-O7. The six-membered ring assumes a slightly distorted twist conformation while the fused five-membered ring is in the half-chair conformation. The isopropylidene moiety is in the envelope conformation. PMID- 1863429 TI - Interactions between fluoride and plaque in the remineralization of enamel caries like lesions. AB - The effect of fluoride and plaque, separately and together on the remineralization of early artificial caries lesions was studied in a group of volunteers in a double-blind randomized study design. Artificial caries lesions produced in slabs of human enamel were mounted buccally in silver bands cemented bilaterally to the mandibular first molar teeth. Volunteers wore the bands for two 2-week periods, rinsing daily with either a placebo or a 500 ppm fluoride mouthrinse. Plaque accumulation was encouraged by placing Dacron gauze over one of each pair of slabs. Sections were cut from the lesions and analyzed by microradiography followed by microdensitometry and image analysis. Microdensitometric data revealed that non-significant increases in mineralization had occurred in all of the test groups. However, the image analysis results indicated that significant remineralization had occurred in lesions after 2 weeks on the fluoride rinse regimen, with no significant remineralization in lesions exposed to the placebo. The presence or absence of plaque over the lesions had no effect on the amount of remineralization induced on the fluoride rinse regimen. PMID- 1863430 TI - Effect of etching times and mechanical pretreatment on the enamel of primary teeth: an SEM study. AB - The purpose of this SEM study was to evaluate the micromorphology of the enamel of primary teeth etched for 15, 30, 60 or 120 seconds, with or without previous mechanical pretreatment. A total of 40 non-carious primary teeth were used. One half of the facial surface of each tooth was ground with a #169 diamond bur mounted in a high-speed handpiece. The other half was left intact. A 37% phosphoric acid gel was applied with a small brush to the facial enamel and left undisturbed for 15, 30, 60 or 120 seconds. Each group had 10 teeth. All teeth were examined under the SEM. The results revealed that etching time had no significant effect on the micromorphology of the enamel surface of primary teeth. Grinding the enamel with the diamond bur before etching produced a uniform distribution of prismatic structure regardless of the etching time. If the enamel surface was not ground, a "coral-like" porous retentive surface was apparent in most of the cases with no defined prismatic structure. The term "coral-like" enamel is a better descriptor of the etched "prismless" enamel surface while observed under the SEM. PMID- 1863431 TI - Enamel softening with Coca-Cola and rehardening with milk or saliva. AB - Rehardening effects by cow's milk and by secreted saliva were investigated, in situ, following softening of human enamel with an acidic beverage (Coca-Cola). Volunteers wearing orthodontic removable appliances participated in the study. The intra-oral test was chosen for measuring microhardness of enamel slabs inserted into the dental appliance. The softening and the rehardening degrees were defined as the alterations between initial- and experimental-microhardness value at the enamel surface. In addition, SEM photos were prepared from the initial and experimental stages. Exposure of enamel slabs to the acidic beverage during 1 hour had a softening effect as expressed by the hardness decrease and visualized by the SEM photo. Rehardening effects following milk or saliva exposures respectively were evident, presumably due to deposited organic and mineral material on the enamel surface. PMID- 1863432 TI - Effects of ferric and aluminum oxalates on dentin permeability. AB - The purpose of this study was to compare the efficacy of ferric oxalate, aluminum oxalate, or Tenure dentin conditioner, a marketed product containing aluminum oxalate, at reducing the permeability of human dentin in vitro. Topical treatment with these acidified agents or 2.5% nitric acid for 10, 30, or 60 seconds was compared. The results indicate that 10-second treatments of dentin with all agents increased dentin permeability. Extending the treatment to 30 seconds produced a decrease in dentin permeability for acidified aluminum and ferric oxalate with 60-second treatments being even more effective. Treatment with Tenure dentin conditioner for 60 seconds did not reduce dentin permeability as well as treatment with the other oxalate salts. PMID- 1863433 TI - Effect of interchanging automatic mixing tips on void formation for an automixed addition silicone impression. AB - This study examined the effect of interchanging mixing tips on void formation for impressions of an automixed addition silicone material. The impressions were made of a series of stainless-steel cylinders by two dentists. The voids were counted at a predetermined site with a binocular microscope. The results showed that there were no significant variations in the number of voids in impressions of the automixed addition silicone using the three different mixing tips. However, one dentist made impressions that had substantially less voids for all three mixing tips. PMID- 1863434 TI - Biocompatibility of a glass ionomer luting agent. 2. Crown cementation. AB - In this experiment, 64 crown preparations were made in four primates. Final impressions, die fabrication, wax patterns and castings were achieved using conventional established clinical and laboratory techniques. Vented and unvented crowns were cemented with a glass ionomer cement (GI) and a zinc phosphate cement (ZOP). Some preparations were protected with calcium hydroxide liquid. On the same animals, in teeth not used for crowns, Class V cavities were prepared and GI and ZOP inserted by means of a pressure technique imitating hydraulic pressure generated during crown cementation. After periods of 5 and 60 days, the animals were sacrificed, the jaws dissected, fixed in formalin and prepared for histological evaluation. Of the 64 cemented crowns, one was unaccounted for. Of the unvented crowns with GI (5 days), vented crowns with GI (60 days), unvented crowns with ZOP (60 days), Class V with ZOP (5 days) and GI (60 days) with a remaining dentin thickness (RDT) of less than 1 mm, inflammatory responses of greater than or equal to 1 degree (on a scale 1-4 degrees) were observed. The use of liquid calcium hydroxide reduced the intensity of the reactions, in particular when small RDTs were present. It can be concluded that when RDTs of 1 mm or more were present, the cements in all groups were non-toxic. When it is estimated that the RDT is less than or equal to 1 mm, the use of a calcium hydroxide liner is recommended. Placement of luting agents in Class V preparations with pressure resulted in reactions resembling crown cementation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863435 TI - Respirability, microstructure and filler content of composite dusts. AB - Dusts were generated from five composites, with two different shades each. Between 54 and 70 mass percent of the dust (60 to 92% of the particles) collected was respirable. The average particle size collected was 3.97 microns by mass (0.9 microns by number of particles). Between 14 and 22% of the dust generated was respirable. Filler content of the respirable dust particles was within 3 mass percent of the amount of filler in each cured composite. Powder x-ray diffraction revealed that respirable dust particles collected from composites reported to contain crystalline silica fillers contain the same crystalline silica. The results indicate that improperly protected dental personnel who are regularly exposed to composite dusts generated during high-speed finishing of composites containing quartz filler may be at risk for developing silicosis. Dental personnel should wear masks specifically designed to filter respirable silica when finishing composite restorations with high-speed instrumentation. PMID- 1863436 TI - Otitis media with effusion in children. Binaural hearing before and after corrective surgery. AB - The masking-level difference (MLD) was investigated in a group of children having no known history of ear disease, and a group of children having a history of otitis media with effusion and hearing loss. The MLD is a psychoacoustic measure of the sensitivity of the auditory system to subtle interaural difference cues of time and amplitude and relates to the ability of the listener to detect and to recognize signals in noisy backgrounds. In the otitis media with effusion group, MLDs were measured both before and 1 and 3 months after the placement of pressure equalization tubes. The MLDs were often abnormally small in the otitis media with effusion group before surgery, when hearing loss was present. Significantly, MLDs sometimes remained abnormally small after surgery (after normal hearing had returned). The postsurgery MLD was particularly likely to be abnormally reduced in subjects who had experienced asymmetric losses of hearing. PMID- 1863437 TI - Composite free flaps in oromandibular reconstruction. Review of the literature. AB - The transfer of vascularized bone containing free flaps is the most effective method of achieving a functional oromandibular reconstruction in the primary setting. All of the reported series on mandibular reconstruction using microvascular free flaps, totaling 513 cases, are reviewed. The collective success rates of free flap transfers compiled from these series have steadily increased to 96% during the latter portion of this review. The experimental studies demonstrating the viability of vascularized bone following an ischemic insult are presented. The issues regarding primary and secondary mandible reconstruction are reviewed. Each of the eight donor sites for vascularized bone are discussed and rated with respect to the ideal qualities of the bone and soft tissue components of a composite free flap to achieve an optimal oromandibular reconstruction. PMID- 1863438 TI - Oromandibular reconstruction using microvascular composite free flaps. Report of 71 cases and a new classification scheme for bony, soft-tissue, and neurologic defects. AB - We describe 71 cases of oromandibular reconstruction using microvascular composite free flaps. There was an overall flap success rate of 94%, while 97% of the patients in this series had their mandibles reconstructed with free vascularized bone flaps. Fifteen patients were rehabilitated with implant-borne dental prostheses. Primary repair of discontinuity defects of the inferior alveolar nerve using a variety of nerve grafts was performed in 16 patients. A new classification scheme for composite defects of the oral cavity involving bone, soft tissue, and neurologic defects is proposed and applied in the description of each of the patients in this series. PMID- 1863439 TI - Immediate mandibular replacement using reconstruction plates. AB - Mandibular reconstruction at the time of tumor resection remains a surgical dilemma. Primary reconstruction allows for immediate reconstitution of mandibular form and function. Various methods have been attempted, but none enjoys uniform success. With advances in the field of microvascular surgery have come numerous options in replacing these defects. These procedures, however, require special surgical teams and are associated with an increase in operative time as well as morbidity at the donor site. An alternative method involves the use of mandibular reconstruction plates to bridge the defect between segments. This review focuses on 19 patients whose jaws were reconstructed in this fashion. Although not free of complications, mandibular plate reconstruction offers the advantages of (1) lack of donor site morbidity, (2) expediency, (3) excellent mandibular contour, and (4) the ability to reconstruct the condyle when necessary. The technique, results, and complications associated with this procedure are discussed. PMID- 1863440 TI - 'Medial maxillectomy' for lateral nasal wall neoplasms. AB - Lateral rhinotomy and "medial maxillectomy," an en bloc resection of the medial maxillary sinus, ethmoid sinus with the lamina papyracea, medial orbital floor, and lacrimal fossa-duct, have been advocated for lateral nasal wall neoplasma. Experience with 35 (of 41) patients followed up at least 30 months (median, 57 months) postoperatively is reported. There was a 9% recurrence for benign tumors and 15% for malignant neoplasms, the latter only in the patients with nonmelanoma malignant neoplasms not receiving postoperative radiotherapy. The most frequent complications were cavity crusting, epicanthal scarring, and epiphora. PMID- 1863441 TI - Suprahyoid pharyngotomy for oropharynx cancer including the tongue base. AB - Suprahyoid pharyngotomy has been utilized as the standard approach to tongue base cancer not involving the larynx or mandible for the last 6 years at the Department of Veterans Affairs Medical Center, Boston, Mass. Review of 15 patients revealed that all had advanced disease (stage III and stage IV); 14 cases involved the tongue base, and one was on the posterior pharyngeal wall. By following the hyoepiglottic ligament, precise entry into the vallecula was routine. No injuries of vital neurovascular structures or compromised tumor margins were present; one tracheotomy was performed. Primary closure without the use of flaps was accomplished in 14 of 15 patients. No locoregional recurrences were found, with a median follow-up of 25 months. However, two patients died of another unrelated cancer, and two patients died of a myocardial infarction unrelated to their surgery. Suprahyoid pharyngotomy is a familiar approach often utilized during laryngectomy. In our experience, it provides excellent exposure of the oropharynx, can be combined with a transoral approach to avoid mandibulotomy without precluding this option, allows for simple reconstruction, and has a low complication rate. PMID- 1863442 TI - Osteogenic sarcoma of the head and neck. The UCLA experience. AB - Eighteen cases of osteogenic sarcoma of the head and neck were treated at our institution between 1955 and 1987. The patients' ages ranged from 5 to 73 years, with a median age of 28 years. The sex distribution was equal. Follow-up ranged from 1 to 276 months, with a median of 79 months. The primary site of the tumor was the mandible in nine cases, maxilla and paranasal sinuses in six, skull in two, and orbit in one. Six of 18 patients were free of disease with greater than 5 years of follow-up. Four of the six received combined surgery, radiation therapy, and chemotherapy as their primary treatment. Of the five patients treated with surgery alone, four suffered recurrences, one of whom was salvaged with further surgery and chemotherapy. Five patients were treated initially without surgery. They received radiation therapy with or without chemotherapy; all five developed local recurrence. We conclude that osteogenic sarcoma of the head and neck is an aggressive tumor, prone to both local and distant failure. Based on our series and from published experience involving the extremities, osteogenic sarcoma of the head and neck should be managed with multimodality therapy. PMID- 1863443 TI - Gax collagen as an adjunctive measure for the incontinent myomucosal shunt. AB - Clinically important aspiration following the creation of a phonatory myomucosal shunt has occurred in 16% of our cases. Gax collagen was used in three cases therapeutically with excellent results. We report the technique used, the properties that make it efficacious, and the case specifics. PMID- 1863444 TI - Gender influences subsite of origin of laryngeal carcinoma. AB - The relationship of gender to laryngeal cancer is not well understood. We analyzed 688 laryngeal cancers diagnosed in Kansas from 1980 through 1989 for sex differences in subsite distribution (glottis, supraglottis, subglottis, and laryngeal cartilage) as well as survival, histologic grade, and age at diagnosis. The ratio of glottic to supraglottic tumors was 22.12:1 in men and 0.56:1 in women, a highly significant difference. Survival in glottic tumors was significantly better than in supraglottic tumors, but survival was not significantly better for women than it was for men. Glottic tumors were significantly more likely than were supraglottic tumors to be of low-grade malignancy for all subjects and for male subjects alone, but not for female subjects alone. Women were younger at time of diagnosis than were men, but not significantly so. Gender is an important factor in the genesis of laryngeal cancer. PMID- 1863445 TI - Modified approach for ethmoid and anterior skull base surgery. AB - The use of combined craniofacial resection is well established for tumors of the ethmoid bone and the anterior aspect of the base of the skull. Mobilization of the medial fronto-orbital ridge improves the transbasal approach and can be performed with a monobloc bone flap. We describe an en bloc bifrontal craniotomy including the supraorbital ridges and the nasal bones. This provides a wider angle of approach to the anterior aspect of the base of the skull than any other method and avoids retraction of the frontal lobes. This type of bone flap procedure can be performed after a wide periosteal dissection in the coronal area of the scalp alone, without facial skin incision. PMID- 1863446 TI - Nasal tip projection. Quantitative changes following rhinoplasty. AB - Fifty-one patients were enrolled in a study and underwent primary rhinoplasty. Serial nasal tip projection measurements were made preoperatively, intraoperatively, and 6 months postoperatively. Actual changes in measured nasal tip projection were evaluated with respect to preoperative goals and specific procedures used to accomplish these goals in the nasal tip. Several useful observations are made from these data: (1) The most important components of nasal tip projection in the postsurgical nasal tip are the medial crura, their attachment to the caudal septum, and the presence of additional cartilaginous grafts placed between the medial crura or beneath the crural feet. (2) Actual nasal tip projection will decrease postoperatively, unless measures to increase the length and strength of the medial crural segment are taken (ie, McCollough modified Goldman tip procedure, cartilage struts, plumping grafts, etc), regardless of the preoperative goal. (3) The double-dome unit procedure is effective in narrowing the wide or bulbous lobule but alone does not permanently increase nasal tip projection. (4) Conservative tip procedures, such as a complete strip, result in decreased nasal tip projection and should therefore be used in patients in whom retrodisplacement of the nasal tip is the intended result. PMID- 1863447 TI - Punctal occlusion and blepharoplasty in patients with dry eye syndrome. AB - Blepharoplasty and inferior punctal occlusion were performed on 24 consecutive patients with dry eye syndrome. Fifteen patients (62.5%) had symptomatic dry eye syndrome preoperatively and nine patients (37.5%) had asymptomatic dry eye syndrome diagnosed during the preoperative workup (subclinical dry eye syndrome). After surgery, nine patients (37.5%) had improvement of their dry eye syndrome, 10 patients (42%) were unchanged, and two patients (8%) had worsening of their dry eye syndrome. A third patient had worsening of the dry eye syndrome 6 months postoperatively when her puncta reopened. Two patients (8%) had increased irritation only when wearing contact lenses, but in one patient this resolved 6 months after surgery. Thus, although a significant number are improved, a few patients will have worsening of dry eye syndrome after blepharoplasty and inferior punctal occlusion. PMID- 1863448 TI - Crack cocaine burns of the larynx. AB - Burn injuries of the larynx are a previously unrecognized complication of cocaine abuse. The clinical presentations and magnetic resonance imaging findings of two patients are presented. Recognition of this entity is important to avoid errors in diagnosis and in management. PMID- 1863449 TI - Histiocytic necrotizing lymphadenitis (Kikuchi's disease). AB - Histiocytic necrotizing lymphandenitis (HNL), or Kikuchi's disease, is a newly recognized disease of unknown origin that causes cervical lymphadenitis, usually in young women. Initially described in Japan, cases of HNL are being reported in the United States and other western countries with increasing frequency. Symptoms of HNL include tender cervical adenopathy, fever, weight loss, and night sweats. Laboratory studies reveal leukopenia with relative granulocytopenia and lymphocytosis. Lymph node biopsy reveals areas with frank cellular necrosis, karyorrhexis, and absence of plasma cells. The histologic features of HNL are distinctive but can be confused with those of lymphoma. We describe two cases of HNL and present recommendations for diagnosis and treatment. PMID- 1863450 TI - Pathologic quiz case 1. Tracheal agenesis (TA) (Floyd's type II). PMID- 1863451 TI - Effectiveness of radon control techniques in fifteen homes. AB - Radon control systems were installed and evaluated in fourteen homes in the Spokane River Valley/Rathdrum Prairie and in one home in Vancouver, Washington. Because of local soil conditions, subsurface ventilation (SSV) by pressurization was always more effective in these houses than SSV by depressurization in reducing indoor radon levels to below guidelines. Basement overpressurization was successfully applied in five houses with airtight basements where practical-sized fans could develop an overpressure of 1 to 3 Pascals. Crawlspace ventilation was more effective than crawlspace isolation in reducing radon entry from the crawlspace, but had to be used in conjunction with other mitigation techniques, since the houses also had basements. Indoor radon concentrations in two houses with air-to-air heat exchangers (AAHX) were reduced to levels inversely dependent on the new total ventilation rates and were lowered even further in one house where the air distribution system was modified. Sealing penetrations in the below grade surfaces of substructures was relatively ineffective in controlling radon. Operation of the radon control systems (except for the AAHX's) made no measureable change in ventilation rates or indoor concentrations of other measured pollutants. Installation costs by treated floor area ranged from approximately $4/m2 for sealing to $28/m2 for the AAHX's. Based on the low electric rates for the region, annual operating costs for the active systems were estimated to be approximately $60 to $170. PMID- 1863452 TI - [Research by the Fondo de Investigacion Sanitaria in the neurosciences and its impact in European programs]. PMID- 1863453 TI - [Primary intraventricular hemorrhage in the adult]. AB - Forty two instances of primary intraventricular hemorrhage (PIVH) out of overall 592 cases of intracerebral hemorrhages diagnosed by CT in 1980-1989, to evaluate the general prognosis attributable to PIVH and its factors. The mortality rate was 23.8%, and persistent residual disability was small or absent in 59.5% of patients. The prognosis was influenced by the clinical status at admission and the magnitude of ventricular bleeding. We conclude that PIVH is comparatively benign. PMID- 1863454 TI - [Multifocal demyelinating neuropathy with persistent conduction blocks and continuous muscular activity]. AB - A patient developed an initially asymmetric sensory-motor neuropathy, with definite predominance in upper limbs. The examination also disclosed a markedly impaired muscle relaxation. The neurophysiological study showed conduction blocks with continuous muscle activity consisting of myokymias fasciculations and muscle cramps which disappeared after the anesthetic block of the distal nerve segments. In the sural nerve biopsy significant abnormalities were not found. After prednisone and carbamazepine therapy in usual doses the symptoms reverted and the conduction blocks persisted. Neuropathy with persistent conduction blocks is an uncommon disease which exceptionally results in a clinically apparent syndrome of continuous muscle activity. Its recognition is important, as symptoms can disappear after correct therapy. PMID- 1863455 TI - [Spongiform encephalopathy and multisystemic degeneration]. AB - Onset of a neurological disease was coincidental in two members of a family. The mother died at the age of 57 and her daughter at the age of 27 years. Clinically the disease was manifested by cerebellar ataxia, visual disturbances, dystonic movements and intellectual impairment which appeared very later in the course of the disease in the younger patient. Myoclonus was only observed in the mother. The EEG examination revealed non-specific abnormalities. CT scans disclosed severe cerebellar atrophy and reduced size of the pons in the daughter. The duration of the disease was 7 months in the mother and 3 years in her daughter. The neuropathological examination showed degeneration of the thalamus, substantia nigra and inferior olives, together with loss of Purkinje cells and axonal torpedos in the granular layer of the mother. Olivopontocerebellar atrophy, atrophy of the thalamus and substantia nigra, associated to typical spongiform encephalopathy of the cerebral cortex, amygdaloid complex and striatum occurred in the daughter. These observations let us to comment whether multisystemic atrophies may be fortuitously associated to different prion-induced encephalopathies, or may be found in the context of spongiform encephalopathies. PMID- 1863456 TI - [Proposal for a protein redistribution diet in the control of motor fluctuations in Parkinson's disease: acceptance and efficacy]. AB - Some patients with Parkinson's disease (PD) and fluctuations of motor response to levodopa therapy may benefit by avoiding proteins during daytime meals, while leaving them unrestricted until bedtime. The acceptance and benefits of a protein redistribution diet (PRD) was studied in 26 PD patients whose fluctuations were refractory to current medications. Only 15 patients (57.2%) were still adhered to the diet 3 months later. Non compliance was more often justified on the basis of the changes in alimentary habits, as a too heavy supper (37%), scanty variation of meals (27%) and difficulties in preparing the diet (18%), rather than do to adverse effects of the diet on PD which occurred in 2 patients (exacerbation of the dyskinesias and lack of effectiveness, respectively). The PRD proved beneficial to 67% of those patients able to keep adhered to it, 4 patients shifting to stable responses. Five diet-benefit patients who performed daily "on off" charts decreased their mean daily "off" time from 13 to 3 % (p less than 0.05), but "on" time quality remained unimproved by the diet. The PRD introduces a heavy change in dietary habits which is not readily accepted by many PD patients. However, the fact that fluctuations disappeared in one fourth of those able to maintain the diet warrants a closely supervised, short-time trial to identify those in whom benefits override the inconveniences of such new changes in the patient's way of life. PMID- 1863458 TI - [Locked-in syndrome]. PMID- 1863457 TI - [Transitory locked-in syndrome]. PMID- 1863459 TI - [Mesencephalic hematoma with a benign course]. PMID- 1863460 TI - [Hemifacial tonic contraction secondary to an extra-axial tumor of the posterior fossa]. PMID- 1863461 TI - [Platelets and cerebral ischemia]. PMID- 1863462 TI - [Epidemiology of multiple sclerosis in Asturias]. AB - An epidemiological study of multiple sclerosis carried out in Gijon (Principado de Asturias). It had the methodological peculiarity of having been performed in a reduced population of 81,462 individuals selected from the primary health care centers from which they depended. This permitted a better case finding and both a prospective and retrospective investigation. In the prospective period, the incidence found was 0.49/100,000/year, while it was 1.59 in the retrospective period. The reasons for this difference are discussed. The prevalence was 23.32/100,000. We attribute the fact that this rate is higher than that previously reported for Spain to methodological and perhaps geographical reasons. PMID- 1863463 TI - [Symptomatic chronic subdural hematoma. Analysis of 68 cases treated surgically with small craniotomy and placement of a closed drainage system]. AB - Sixty eight cases of chronic subdural hematoma (CSDH) surgically treated (December 1984-December 1988) with twist drill craniostomy (3-4 mm) and application of a closed drainage system (CDS) are reviewed. The patients were distributed in four groups depending on the density of the hematoma: hypodense (36 cases), isodense (6 cases), of mixed density (22 cases) and hyperdense (4 cases). In about one third of patients (25 cases) the duration of symptoms was shorter than one week, in 21 cases it was between one week and one month, and in 22 patients it was longer than one month. 77.95% of cases had a preceding head injury. Headache and motor deficits were the leading symptoms, being present in 43 (63.2%) and 42 (61.7%) cases, respectively. Twelve patients (17.6%) were comatose on admission. Twelve patients required reoperation. Six patients died (8.8%). The preoperative neurological status and associated systemic diseases influenced the outcome. We think that limited craniostomy with CDS is the therapy of choice for symptomatic CSDH. PMID- 1863464 TI - [Effect of atmospheric factors on the presentation of cerebrovascular accidents]. AB - The concept of meteoropathy implicates the atmospheric properties as determining or at least provoking causes of different disease conditions. Thus, we know that changes in temperature, atmospheric pressure and humidity rate are associated with a higher incidence of stroke presentation. Considered as a whole, these three atmospheric factors have been associated with the several clinical diagnoses of stroke. A higher presentation rate of stroke has been found when the three following facts concurred: a reduction of 10 degrees (C) in the temperature of the preceding day, an increase of the atmospheric humidity rate from 20% to 60% on the day of stroke, and an increase in atmospheric pressure of 6 mlbs from the preceding day (s = 0.0000). In addition, a higher rate of presentation of stroke was found when the difference in atmospheric pressure was 16 mlbs between the day of stroke and the preceding one (s = 0.049). Also, when the atmosphere humidity rate increased from 20% to 60%, the difference in mean temperature between the day of stroke and the preceding one was 3 degrees (C), and the atmospheric pressure increased in 6 mlbs, the incidence of stroke was higher (s = 0.007). We compare these findings with those from other authors. PMID- 1863465 TI - [Cerebral infarction in young people: etiological and diagnostic aspects]. PMID- 1863466 TI - [Recurrent amyotrophic neuralgia with an unusual clinical expression. Clinical and electrophysiological study]. AB - Neuralgic amyotrophy (NA) is an entity with great variability in its neurological expression. The patient reported here developed symptoms of NA one year before admission, with anterior interosseous nerve palsy. At the time of examination she reports pain in the left upper limb followed by sensory loss over lateral antebrachial cutaneous nerve. Electrophysiologic examination showed signs of chronic denervation in the right anterior interosseous nerve muscles, and reduced amplitude of the sensory nerve action potential of the left lateral antebrachial cutaneous nerve. This case confirms the variety of the nerve involvement in NA, and suggests axonal focal lesions of nerve fascicles or individual peripheral nerve affectation. PMID- 1863467 TI - [Multiple cerebral infarctions during a migraine attack]. AB - Two cases of migraine complicated with ischemic cerebral infarct are reported. Both met the established criteria for the diagnosis: definite history of classical or common migraine, development of an ischemic infarct during the crisis, duration of deficit lasting more than 24 hours and absence of other causes of cerebrovascular disease. Several laboratory examinations were carried out: routine blood tests, coagulation study, immunological study, serological tests for syphilis, ECG, echocardiogram, cerebral CT, and nuclear magnetic resonance imaging and angiography. The most remarkable finding in these two patients were multiple cerebral infarcts in different vascular territories. This fact is exceptionally reported in the literature. The clinical outcome of the patients was characterized by the virtually complete reversal of neurological deficit. PMID- 1863468 TI - [Myasthenia and dysphagia]. PMID- 1863469 TI - [Proportional hemi-acroplegia and localization to the pyramidal tract of the internal capsule]. PMID- 1863470 TI - Expression in yeast of a cDNA clone encoding a transmembrane glycoprotein gp41 fragment (a.a. 591-642) bearing the major immunodominant domain of human immunodeficiency virus. AB - A cDNA clone corresponding to the gp41 gene fragment nucl. 7573-7730 of the human immunodeficiency virus type 1 (HIV-1) was selected from a random HIV-1 genomic library expressed in yeast. This clone encodes a 52-residue long peptide (amino acid (a.a.)) 591-642) bearing the major immunodominant domain (a.a. 598-609) of the HIV-1 transmembrane glycoprotein gp41. Expression of the recombinant peptide pSE-env591-642 was driven by the alpha-mating factor leader sequence contained in a plasmid pSE-x allowing the synthesis and secretion of foreign gene product in Saccharomyces cerevisiae. Time-course analysis of the secretion into culture medium revealed an optimal production of the glycoprotein fragment at 28-30 h with no observable cytotoxicity. The secreted peptide is highly glycosylated with NH2-terminal heterogeneity probably due to different post-translational modifications. The secreted peptide shows an extreme antigenicity since in ELISA assays, as few as 5 microliters/well of crude supernatant are sufficient to obtain a strong detection by monoclonal antibodies or by 100% of sera from HIV infected individuals. The purified glycopeptide pSE-env591-642 binds to a monoclonal antibody directed against the immunodominant epitope (a.a. 603-609) with an affinity similar to that of the complete glycoprotein gp160 (Kd values within the 10(-10) M range) and with a 100-fold higher affinity than that of a linear peptide fragment SP-env584-609. These results indicate that overexpression in yeast can efficiently provide an abundant source of highly antigenic gp41 protein fragment pSE-env591-642 which retains the antigenic properties of the native gp160 protein. Such a recombinant peptide should therefore be considered as a good candidate for antigen in HIV detection tests. PMID- 1863471 TI - Variations in cytotoxicity and isoenzyme patterns of uncloned and cloned cultures of axenic Entamoeba histolytica. AB - Five clones of axenic Entamoeba histolytica (HMI) grown as discrete colonies in semisolid agar medium were adapted in liquid medium and labelled as HMI-C121, HMI C131, HMI-C143, HMI-C144 and HMI-C145. The clone HMI-C121 was more cytotoxic to the cultured Baby Hamster Kidney (BHK) cells while all other clones were significantly (P less than 0.001) less cytotoxic as compared to the cloned HMI C121 and uncloned E. histolytica (HMI). The uncloned Indian axenic E. histolytica (KCG:0986:11) as well as E. histolytica (NIH:200) cultures were significantly (P less than 0.001) less cytotoxic to cultured BHK cells. No difference in the electromobility of maleate NADP oxidoreductase (ME) or glucophosphate isomerase (GPI) isoenzyme in the lysates of all the cloned and uncloned cultures of E. histolytica was observed. The clones HMI-C121, HMI-C131, HMI-G143 and HMI-C144 had three bands of hexokinase (HK) while all uncloned cultures and one of clones, HMI-C145 had only two bands. Though cloned and uncloned cultures had a single PGM band, the relative electromobility (rf) of phosphoglucomutase (PGM) for clone HMI C131, HMI-C143 HMI-C144 was relatively less (rf 0.075) and these were also significantly (P less than 0.001) less cytotoxic to BHK cells as compared to clone HMI-C121. It is felt that axenic E. histolytica culture consists of several populations (clones) and expression of isoenzymes pattern or cytotoxic potentials would depend upon the population which predominantly multiples and outgrows other populations in the culture system. PMID- 1863472 TI - Circulating immune complexes in experimental syphilis and their relation to immunological response against Treponema pallidum. AB - It was found that circulating immune complexes (CIC) were formed in rabbits at different times after infection with Treponema pallidum. The CIC which appeared at the beginning of the disease were short-lived (2-6 weeks) but those appearing later than 20 weeks after infection remained for 10-25 weeks. CIC contained both IgM and IgG classes of immunoglobulin. The antibodies present in CIC were found to be specific and nonspecific for T. pallidum. The presence of CIC led to a marked decline of treponemal antibodies in rabbit sera. The cell-mediated immune response measured by the macrophage migration inhibition (MMI) test at the beginning of the disease (up to 12 weeks) was not decreased. However, when syphilis lasted for more than 14 weeks and when CIC were formed mainly from IgG, a distinct decrease in the ability of lymphocytes to cause MMI was observed. These findings strongly suggest that IgG-complexes suppress the immunological responsiveness of lymphocytes against T. pallidum which in turn facilitates the multiplication of treponemes in the host. PMID- 1863473 TI - Color Doppler sonography of the scrotum. AB - Color Doppler sonography is a noninvasive, rapidly performed, and relatively inexpensive imaging technique for use in the diagnosis of scrotal pathology. Its major and proven role is in the evaluation of patients with acute scrotal pain, for which it is likely to become the primary imaging modality. Further work is needed to determine whether color Doppler is a useful diagnostic adjunct in evaluating patients with varicoceles and scrotal masses. PMID- 1863474 TI - Acute diseases of the scrotum. AB - Several imaging modalities are available for evaluating the patient with acute scrotal pain. Until recently, scintigraphy was the initial procedure of choice in most patients, as it was the only noninvasive technique for determining integrity of blood flow to the testicle. Ultrasound was valuable when the scintiscan was inconclusive or in the setting of scrotal trauma. With the advent of color Doppler sonography, information about both structure and blood flow can be obtained by means of a single imaging study. If initial promising results with this newer technique are borne out, color Doppler is likely to become the primary diagnostic test in patients with acute scrotal pain. The role of MRI and MRS has yet to be defined. PMID- 1863475 TI - Ultrasound of the nonacute scrotum. PMID- 1863476 TI - The penis. PMID- 1863477 TI - Evaluation of impotence. PMID- 1863478 TI - Imaging of the external male genital tract. PMID- 1863479 TI - Imaging of the external male genital tract. PMID- 1863480 TI - Magnetic resonance imaging of the scrotum. AB - MRI demonstrates exquisite anatomical detail of the entire scrotum and inguinal region, adding a new dimension to the assessment of scrotal disease. MRI allows the recognition and distinction of intrascrotal structures and clearly displays their alteration in disease states. MR interpretation is based on a constellation of intrascrotal findings. A specific diagnosis frequently can be made from the MR results combined with the clinical presentation. On the other hand, MR is more expensive and time consuming than sonography and access in many geographic areas is still limited. MRI may be helpful when ultrasound is inconclusive or fails to demonstrate a clinically suspected lesion. In the author's experience, when MR has been the first imaging modality used, ultrasound has not been needed to reach a diagnosis. PMID- 1863481 TI - [Biochemistry of galactosialidosis]. PMID- 1863482 TI - [Effects of cerebral cortical lesions on the ipsilateral thalamus]. AB - An injury to the central nervous system causes a focal logical disturbance, and further may affect the blood flow, metabolism, and function of other brain regions. Recent studies using PET or SPECT have demonstrated that impairment of regional hemodynamics or metabolism in cerebrovascular disease involves not only the site of the lesion itself but also more remote areas. Although depression of the metabolism of the ipsilateral thalamus in patients with cerebral cortical lesions has been shown by PET study, the pathophysiological implications of this remain unclear. The functional and morphological effects of cortical infarcts on the ipsilateral thalamus were studied by assessment of cerebral blood flow using 123I-IMP SPECT and by determining atrophic changes on CT or MRI. Nine out of 17 patients with cortical infarcts showed hypoperfusion of the ipsilateral thalamus, especially patients with larger infarcts involving the frontal or parietal cortex. Thalamic hypoperfusion persisted from early after the insult to several months or even years later. In addition, atrophy of the ipsilateral thalamus was not uncommon following larger cortical infarcts. This tended to be evident about 1 year after the infarct and progressed over several years. Furthermore, atrophic changes in the thalamus was often demonstrated in such patients as hypoperfusion in the later stages. Thus, cortical lesions had functional and morphological effects on the ipsilateral thalamus ranging from early hypoperfusion to later irreversible atrophic changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863483 TI - [Estimation of prognosis in patients with putaminal hematoma]. AB - In order to determine the factors affecting the functional prognosis of operated putaminal hematoma patients, the relationship between the final outcome and the acute stage clinical factors were analyzed by the use of multimodality analysis method (Hayashi's Qualification Type 2). Forty-five consecutive cases who admitted to and operated on during the last two years were included in this study (30 male and 15 female patients, the distribution of age was 40 to 75 years old). Clinical factors just prior to surgery were collected from the case record and categorized to calculate the Pearson's product moment correlation coefficient against the Glasgow Outcome Scale. Five clinical factors with the correlation coefficient above 0.5 (Edinbugh 2 coma scale (0.85), light reflex (0.67), respiratory status (0.61), age (0.58) and the side of the lesion (0.50) were used to apply the Hayashi's Qualification Type 2 analysis. By this method, each categories are given scores so that the different outcome separate maximally. The correct estimation ratio for outcome was 100% for good recovery, 30% for moderately disabled, 50% for severely disabled and 88% for death, over all correct estimation ratio being 69%. The mean scores for each outcome were 1 +/- 0.01 for good recovery (9 cases), 0.74 +/- 0.32 for moderately disabled (10 cases), 0.6 +/- 0.36 for severely disabled (10 cases) and -0.16 +/- 0.37 for dead (16 cases). There were statistical significance (p less than 0.01) between each outcome except for moderately disabled and severely disabled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863484 TI - [Two cases of pure agraphia developed after thalamic hemorrhage]. AB - We have observed two cases suffered from left thalamic hemorrhage, that showed pure agraphia. The first case was a 49 year-old, right handed male, who was educated through 11th grade. The CT scan revealed left thalamic hemorrhage with ventricular casting. The second case was a 48 year- old, right handed male, who was educated through 9th grade. The CT scan revealed left thalamic hemorrhage which is smaller than that of the first case, without intraventricular rupture. With a standard neuropsychological evaluation performed at chronic stage, neither cases showed oral language disorder, apraxia and agnosia. On the Wechsler Adult Intelligence Scale, total IQ of the first and second case were 71 and 80 respectively. Each case developed severe writing disorder. The first case showed severe neographism and scrawl, mild literal paragraphia, which were frequently accompanied with perseveration. The second case showed literal paragraphia and no response, but neographism was not detected. The common characteristics of both cases were; 1) intact copy writing. 2) discrepancy between difficulty in writing "Kana" and that in "Kanji". 3) anosognosia of agraphia. The cerebral blood flow study by 123I-IMP Single photon emission computed tomography revealed low perfusion of the left cerebral hemisphere in both cases. From these findings, we concluded that dysfunction of the left cerebral cortex is responsible for producing agraphia in these cases. PMID- 1863485 TI - [Diffuse axonal injury (DAI) in an autopsy case of head trauma with long survival]. AB - The authors reported a clinico-pathological case survived 11 months after a traffic accident. A 41-year-old man had been hit by a motor car and was found in a state of semicoma. On admission, his consciousness level was III-100 to 200 (Japan Coma Scale). Pupils were isocoric; light reflex was present. Linear fracture of occipital bone was disclosed by Skull X-ray and subarachnoid hemorrhage was revealed on CT scan. This comatose state, lasting 24 hours, slowly improved and eventually he presented the so-called Korsakoff's syndrome until his death. He could not recognized his relatives, only uttered some meaningless words. He was unable to obey simple verbal orders. The patient was incontinent and right pyramidal sign was positive. On repeated CT scans, cerebral ventricles gradually increased in size; especially the enlargement of the fourth ventricle was remarkable. He expired of septic shock caused by bed sores. At autopsy brain weighed 1190 g. Old gloss contusional scars were observed on the bilateral frontal lobes including the orbital area and on the left temporal pole. Gliding contusions were revealed in the subcortical white matter beneath the left superior frontal convolution. Fibrillary gliosis was noted in this region, the deep white matter underlying the left temporal pole and the tissue surrounding the anterior horn of the left lateral ventricle. Nerve fibers were fragmented and lacerated at corpus callosum, anterior commissure and posterior limb of the left internal capsule. Bilateral pyramidal tracts showed mild myelin pallor at the brainstem. Loss of Purkinje cells were observed. This case would correspond to mile type of diffuse axonal injury proposed by Adams and Gennarelli. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863486 TI - [Transient focal abnormalities of MRI and angiographic neuroimaging in status epilepticus: case report]. AB - We reported transient changes in computed tomography (CT), angiography and magnetic resonance imaging (MRI) scans in a patient with status epilepticus, referred to us with a tentative diagnosis of neoplasma based on CT, MRI and angiographic findings, MRI showed increased signal intensity, and CT showed decreased left hemisphere attenuation without enhancement. Two months later, resolution of these radiological and clinical abnormalities had been attained. The transient CT and MRI changes probably represented focal cerebral edema, developing during focal status epilepticus. PMID- 1863487 TI - Desquamative gingivitis: revisited. AB - Desquamative gingivitis is a clinical condition which can encompass a variety of histopathologies. It has not yet been established whether desquamative gingivitis is a distinct hormone-mediated disease entity or a variety of dermatologic diseases (i.e. pemphigus vulgaris, benign mucous membrane pemphigoid, etc.). In this manuscript the epidemiologic, clinical, histopathologic, immunologic and etiologic aspects as well as possible therapeutic modalities for the management of hormone-mediated desquamative gingivitis are examined. PMID- 1863488 TI - Dentist draws on practice for comic ideas. PMID- 1863489 TI - The dilemma of denture contamination. AB - Fourteen dentures from patients requiring new dentures were cultured, treated with Clorox/Cascade/H2O solution, Brushgard, Polident, or distilled water and re cultured. All 14 dentures were contaminated with multiple microorganisms. The Clorox/Cascade/H2O solution was most effective at decontamination with 71 percent of the treated dentures showing no growth of microorganisms. Brushguard showed no growth in 57 percent; Polident showed no growth in 36 percent; and water showed no growth in 14 percent. Of note, Brushgard, Polident, and water-treated dentures also allowed growth and predominance of other microorganisms that did not predominate on the original culture. The results of this study indicate that there is no product on the market at this time capable of consistently disinfecting the denture depths. PMID- 1863490 TI - Dental needs assessment survey: three Florida counties. AB - Dental needs assessment surveys were completed in three Florida counties (1987 - Lee County), (1988 - Pasco County) and (1989 - St. Lucie County). The data collected were then compared with the results from the national caries prevalence surveys in 1979-80 and 1986-87, by individual county and with the combined three county total. Visual tactile examinations were done using the Radlike criteria for the DMFS index and the WHO Treatment Needs Index. Schools were selected based on the percent of students enrolled in the free or reduced lunch program and by geographic distribution. Although there were age group differences within individual counties, the combined data showed every age group except the seven year olds at a lower DMFS mean level than the data from the 1986-87 national survey for Region IV. The differences range from -.20 surfaces in 8-year-olds to .57 surfaces in 13-year-olds. None of the differences were statistically significant from the national surveys. This indicates that these small scale surveys are a reliable method for needs assessment. PMID- 1863491 TI - Hobby turns to 'capturing' yet protecting wildlife. PMID- 1863492 TI - Periodontics 1991. Periodontal regeneration--another opinion. PMID- 1863493 TI - Washington state adopts licensure 'by credentials' rules. PMID- 1863494 TI - What every dentist should know ... before signing a dental provider contract. Stop, read and consider before you sign. PMID- 1863495 TI - Update on oral and maxillofacial surgery. PMID- 1863496 TI - The fluoride risk: fact or fiction? PMID- 1863497 TI - MR imaging of pediatric hematologic disorders. PMID- 1863498 TI - Volumes of chronic traumatic frontal brain lesions measured by MR imaging and CBF tomography. AB - The volumes (ml) of chronic traumatic frontal brain lesions were compared measured "morphologically" with MR imaging (T1 and T2 weighted images) and "functionally" with a tomographic rCBF technique (SPECT with 133Xe i.v.). The T1 volumes varied between 11 and 220 ml. The correlation between T1 and T2 volumes was 0.95, the T2 volumes being 33% larger than T1 volumes (p less than 0.001). The functional SPECT volumes were considerably larger (range 16-324 ml) than the MR volumes. The mean volume difference was 81% between T1 and SPECT images (p less than 0.001), and 35% between T2 and SPECT images (p less than 0.001). Correlations between the MR and SPECT volumes were also higher for T2 than T1 volumes. The volume difference is most likely explained by a functional decrease in regions around the lesion in which no morphologic change visible on MR images had taken place. MR and SPECT volume measurements were positively related to persistent lack of energy and personality changes, but only moderately related to duration of impaired consciousness and neuropsychologic outcome. PMID- 1863499 TI - CT five years after myelographic diagnosis of lumbar disk herniation. AB - Fifty-seven patients were examined with CT 5 years after primary myelography for disabling sciatica and suspected herniated lumbar disk. Forty were in an operated group, 22 with good and 18 with poor results evaluated by occupational handicap (21) 5 years after surgery. Seventeen patients had myelography indicating disk herniation, but were treated conservatively, 9 with good and 8 with poor result. Various spinal dimensions measured at CT did not correlate with outcome. Operated patients had narrower canals than others, and male canals were broader than those in females. Increased amount of scar tissue at L4 level correlated with poor result (p = 0.008). Operated patients with poor result had more advanced lateral stenosis than those treated conservatively (p less than 0.001). Patients with good result after operation had more degeneration observed on CT of erector spinae muscle than those treated conservatively with good outcome. Only 9% of operated patients did not have muscle degeneration. A tendency for more frequent recurrent disk herniations could be seen for conservatively treated patients. The narrowing of the spinal canal 5 years after operation did not correlate with the 5-year outcome. PMID- 1863500 TI - Short pancreas in polysplenia syndrome. AB - Two cases with the polysplenia syndrome also had a short pancreas. To the best of our knowledge the radiologic characteristics of this anatomic anomaly have not yet been reported. Both cases were asymptomatic with regard to their anomaly complex. The radiologic findings of the short "pancreas" are similar to the only pathologic description of this association. The awareness of this association led to the diagnosis of the second case after a few months only. A physician performing ERCP in the polysplenia syndrome should keep in mind the possible presence of the "short pancreas" when the whole length of the pancreatic duct is not visualized. PMID- 1863501 TI - Percutaneous local arterial thrombolytic infusion. Therapeutic effects and complications. AB - All complications occurring in 55 local thrombolytic infusions performed for (sub)acute limb ischemia using streptokinase (SK) in 22 procedures and urokinase (UK) in 33 procedures were recorded. Success was achieved in 74.5% of the procedures. Major complications occurred in 31.8% of the procedures using SK, and in 12.1% of the procedures using UK (p = 0.07). Hemorrhage was the most common major complication and occurred in 27.2% of SK procedures and in 9.0% of UK procedures, a difference which was not significant. Overall, 30 day mortality was 16.3% and procedure-related death was 1.8%. Moderate complications necessitating only the adjustment of drug regimen and minor complications without consequence were observed in 45.5% and 45.5%, respectively, of the SK procedures, and in 57.6% and 66.7% of the UK procedures. PMID- 1863502 TI - Transcatheter embolization of testicular vein for varicocele testis. AB - Percutaneous transcatheter embolization of the testicular vein was performed on 28 patients with angiographically proven varicocele testis. In 2 patients bilateral and in 26 only the left vein was embolized using 3-, 5-, or 8-mm stainless steel coils. All patients had clinically palpable varicoceles and male infertility. The grade of varicoceles improved after embolization in 23 of 28 cases (82%). Effective sperm count increased significantly from 34.5 +/- 44.6 to 65.1 +/- 71.0 following embolization. However, pregnancy was achieved only in one of 28 cases. Technically, the basilic vein approach was felt to be superior to the femoral vein or jugular vein approach for this procedure. PMID- 1863503 TI - Paroxysmal nocturnal hemoglobinuria. Case report of MR imaging and CT findings. AB - A case of paroxysmal nocturnal hemoglobinuria (PNH) is presented in which MR imaging and CT findings were characteristic. The signal intensity of renal cortex was lower than that of medulla on both T1- and T2-weighted imaging. On CT without contrast enhancement the attenuation of renal cortex was higher than that of renal medulla. These findings at MR imaging and CT were the results of a deposition of hemosiderin in the cells of proximal convoluted tubules, and were helpful for diagnosis of PNH. PMID- 1863504 TI - Characteristic fat-fluid level at ultrasonography of ovarian dermoid cyst. AB - An uncommon sonographic pattern was observed in 2 dermoid cysts. An echogenic upper and an echo-free dependent component were separated by a horizontal delineation, an observation that could be reproduced in a laboratory model. We believe that this finding is pathognomonic for a dermoid cyst. PMID- 1863505 TI - Renal effects of iopentol and iohexol after intravenous injection. AB - Renal effects of the 2 non-ionic contrast media iopentol and iohexol were investigated and compared in a double-blind, randomized parallel study where 30 patients received iopentol, and 31 patients iohexol intravenously for abdominal CT. The dosage of contrast medium (350 mg I/ml) was 700 mg I/kg body weight. Only one patient (in the iohexol group) had an increase in serum creatinine of more than 50%. Iopentol and iohexol had no effects on the mean serum values of creatinine, urea, and beta 2-microglobulin (beta 2-MG) nor on creatinine clearance. The urinary excretion of albumin and beta 2-MG was also unchanged. The excretion of the proximal tubular enzymes alkaline phosphatase and N-acetyl-beta glucosaminidase was increased. No significant difference between iopentol and iohexol was found. PMID- 1863506 TI - Absence of functional renal effects of uro-angiographic contrast media on post ischemic rat kidneys. AB - Water soluble ionic contrast media (CM) and glucose 5% were administered to Sprague-Dawley rats 36 hours after bilateral warm renal ischemia for 45 min. In all animals (n = 28) the renal ischemia caused a decrease of the absolute urinary creatinine output. Intra-arterial injection of glucose 5% or CM did not produce different patterns of absolute urinary creatinine output. The serum creatinine increased after 36 hours of reflow. When compared by means of a Mann-Whitney U test to a normal median serum creatinine obtained in a separate group of 22 normal rats, the increase was statistically significant (p less than or equal to 0.01). The serum creatinine medians returned to a normal level after 24 hours. It seems therefore that 45 min of warm renal ischemia and 36 hours of reflow is an insufficient challenge to the rat kidney for the detection of the nephrotoxic properties of CM as opposed to when CM are injected during ischemia. PMID- 1863507 TI - A radiologic reporting system for computer-aided diagnosis with associated database. Hokkaido University Diagnostic Information Processing System--HDIPS. AB - A reporting system which assists radiologists reporting on medical images and calculates alternatives of probable diseases was developed with proven applicability for CT and ultrasonography. The diagnostic information found by radiologists in various types of images is managed as a database in the reporting system and is also transferred to a medical record database, the HIS (Hospital Information System) of Hokkaido University Hospital. The reporting system supports both data conversion and transfer to the host computer of the HIS. The system has processed about 20,000 reports over the last 5 years. Here we present the efficiency of producing reports, the structure of the database, and the hit ratio of calculated diagnoses in this system. PMID- 1863508 TI - Common bile duct cancer with massive necrosis mimicking choledochal dilatation on CT. Case report. AB - Carcinomas of the common bile duct are usually seen as dilatation of the bile duct proximal to a solid mass on CT. In the case reported here, the common bile duct cancer itself mimicked dilated common bile duct on CT because of massive necrosis. In a case of simulating dilated common bile duct on CT, and discrepancy between CT and ultrasonography or endoscopic retrograde cholangiopancreatography, a common bile duct cancer with massive necrosis should be included in the differential diagnosis. PMID- 1863509 TI - Limitations of quantitative CT in corticosteroid induced osteopenia. AB - Single energy spectrum quantitative CT (SES-QCT) was applied for the assessment of the trabecular bone mineral status in patients under long-term corticosteroid treatment. Seventeen renal graft recipients (RGR) and 12 patients receiving corticosteroid treatment for collagen disease were studied. A reduction of about 40% in the spinal trabecular bone density relative to matched controls was found, associated with the corticosteroid administration. Repeated measurements showed significant reduction in density 4 months after transplantation, and an increase in density after graft rejection. Radiologic or clinical evidence of osteopenia in the spine was not found. Other noninvasive techniques, applied in the upper extremities of the RGR, showed only minor bone reduction compared to controls. The findings of the present study suggest that adipose tissue deposition in the spinal trabeculae can introduce errors in the measurements. Therefore, SES-QCT should not be applied during corticosteroid therapy. PMID- 1863510 TI - [NSF's extraordinary national assembly: marathon run with exciting final spurt]. PMID- 1863511 TI - [Our privileged children--observations concerning an emergency clinic]. PMID- 1863512 TI - [Professional Press Award 1990: "Journalen" at the front]. PMID- 1863514 TI - [NSF's extraordinary national assembly: agreement on goals]. PMID- 1863513 TI - [Ally of the deaf. Interview by Marit Fonn]. PMID- 1863515 TI - [NSF's changed structure: blending of the old and new]. PMID- 1863516 TI - [Ladies with experience]. PMID- 1863517 TI - Quantitative measurement of uptake of radiolabeled monoclonal antibody by means of planar data. AB - Data obtained from planar images were used to measure the uptake of monoclonal antibody in organs and tumors. Background counts included in the region of interest were eliminated, and the attenuation of the photons emitted by the radionuclide through the intervening tissues was compensated for. The background counts and the intensity of the attenuation were determined from the results of phantom studies and numerical integration with a personal computer. The quantitative uptake of 111In labeled anti-melanoma Monoclonal Antibody (ZME-018) in a melanoma lesion, the liver, and the bone marrow of a patient was measured by the planar method which we developed. PMID- 1863518 TI - Availability and limitations of thallium-201 myocardial SPECT quantitative analysis: assessment as daily routine procedure for ischemic heart disease. AB - To determine the availability and limitations of the detection of ischemic lesions by stress thallium-201 myocardial SPECT as the daily routine procedure, we compared and evaluated the detectability of the quantitative analysis (%uptake and washout rate (WR)) and visual evaluation in 104 patients with effort angina and 17 normal subjects. Visual evaluation combined with WR analysis resulted in significantly higher sensitivity (88.0%) but lower specificity (60.2%) than the other methods. The sensitivity by visual evaluation was quite low in multivessel disease (MVD), and in the regions supplied by mild coronary stenosis or by the left circumflex artery. These were markedly improved by combining visual evaluation and WR analysis, but sensitivity in the MVD group was unsatisfactory even with this analytic method in comparison with the single vessel disease group. One of the causes of low sensitivity in the MVD group might be the "true negative": No induction of the ischemia in the regions of milder stenosis, or the regions supplied by the collateral coronary flow. We therefore conclude that the combination of visual evaluation as a qualitative analysis and WR analysis as a quantitative analysis, is the most useful daily routine procedure as a screening test for detecting ischemia. PMID- 1863519 TI - A study of ventricular contraction sequence in complete right bundle branch block by phase analysis. AB - Twenty-four patients with complete right bundle branch block (CRBBB) combined with and without left axis deviation (LAD) on ECG, were compared with 17 normal subjects to evaluate the right ventricular contraction sequence and pattern in detail. Blood pool scintigrams were obtained in the left anterior oblique projection, and these images were analyzed by first component Fourier harmonics. In the normal subjects, the phase value distribution representing the pattern of ventricular contraction was almost homogeneous in both the right and left ventricles (RV & LV). In the CRBBB patients without LAD, the phase images showed apparent phase delay in the right ventricle. In the CRBBB patients with LAD, the phase images showed many different contraction patterns varying from normal to RV phase delay, owing to the effects of the hemi-block. Quantitative analysis of the absolute values, showed that the mean (RV-LV) value was 6.6 +/- 8.4 msec in the normal subjects. In the CRBBB patients without LAD, the duration of the QRS complex correlated with the mean (RV-LV) value, whereas no difference was observed between the duration of the QRS complex and the standard deviation of the right ventricle. Using phase analysis the degree of the RBBB can be determined from the phase images, and can be quantitatively analyzed as in electrical studies. PMID- 1863520 TI - The role of gallium-67 imaging in the detection of foci in recent cases of fever of unknown origin. AB - We have assembled data from patients with fever of unknown origin who underwent gallium scintigraphy during the past 5 years in order to obtain a more current sampling of patients, and evaluated the role of gallium scintigraphy retrospectively. Of the 36 patients studied, gallium scintigraphy was positive and contributed to the detection of the foci or fever origins in 17 (47.2%). The ratio of neoplastic diseases with myeloproliferative and with lymphoproliferative disorders was relatively high compared with previous reports. However, gallium scintigraphy did not contribute to the diagnosis of collagen disease. With the ability to detect both inflammatory and neoplastic lesions, gallium scintigraphy was useful in detecting the foci of fevers of unknown origin. PMID- 1863521 TI - Clinical application of indium-111 antimyosin antibody and thallium-201 dual nuclide single photon emission computed tomography in acute myocardial infarction. AB - The significance of indium-111 antimyosin antibody and thallium-201 dual nuclide single photon emission computed tomography (SPECT) was evaluated in 7 patients with acute myocardial infarction (AMI) who underwent emergency coronary angiography with successful revascularization by intracoronary thrombolysis. Indium-111 antimyosin antibody and thallium-201 dual nuclide SPECT was performed 11 to 36 days after the onset of AMI. Antimyosin SPECT images delineated areas of myocardial necrosis in all 7 patients (100%), but planar images detected necrotic areas in only 4 of 7 patients (57%). Peak CPK-MBs of the 3 patients in which no necrotic area was detected by indium-111 planar image showed a tendency to be smaller. Indium-111 antimyosin antibody/thallium-201 overlap was observed in all patients. The area of overlap was at the center of necrosis in 4 patients (2 anterior infarction, 1 inferior infarction, 1 inferolateral infarction) and at the peripheral portion in 3 patients (all 3 had inferior infarction). Indium-111 antimyosin antibody and thallium-201 dual nuclide SPECT is useful in identifying the localization of myocardial infarction and the overlap of these tracers might reflect the presence of salvaged myocardium adjacent to the necrotic myocardium. PMID- 1863522 TI - Benzylic alcohols as stereospecific substrates and inhibitors for aryl sulfotransferase. AB - Aryl sulfotransferase IV catalyzes the 3'-phosphoadenosine-5'-phosphosulfate (PAPS)-dependent formation of sulfuric acid esters of benzylic alcohols. Since the benzylic carbon bearing the hydroxyl group can be asymmetric, the possibility of stereochemical control of substrate specificity of the sulfotransferase was investigated with benzylic alcohols. Benzylic alcohols of known stereochemistry were examined as potential substrates and inhibitors for the homogeneous enzyme purified from rat liver. For 1-phenylethanol, both the (+)-(R)- and (-)-(S) enantiomers were substrates for the enzyme, and the kcat/Km value for the (-)-(S) enantiomer was twice that of the (+)-(R)-enantiomer. The enzyme displayed an absolute stereospecificity with ephedrine and pseudoephedrine, and with 2-methyl 1-phenyl-1-propanol; that is, only (-)-(1R,2S)-ephedrine, (-)-(1R,2R) pseudoephedrine, and (-)-(S)-2-methyl-1-phenyl-1-propanol were substrates for the sulfotransferase. In the case of 1,2,3,4-tetrahydro-1-naphthol, only the (-)-(R) enantiomer was a substrate for the enzyme. Both (+)-(R)-2-methyl-1-phenyl-1 propanol and (+)-(S)-1,2,3,4-tetrahydro-1-naphthol were competitive inhibitors of the aryl sulfotransferase-catalyzed sulfation of 1-naphthalenemethanol. Thus, the configuration of the benzylic carbon bearing the hydroxyl group determined whether these benzylic alcohols were substrates or inhibitors of the rat hepatic aryl sulfotransferase IV. Furthermore, benzylic alcohols such as (+)-(S)-1,2,3,4 tetrahydro-1-naphthol represent a new class of inhibitors for the aryl sulfotransferase. PMID- 1863523 TI - Stereoselectivity of (R)- and (S)-hexahydro-difenidol binding to neuroblastoma M1, cardiac M2, pancreatic M3, and striatum M4 muscarinic receptors. AB - (R)-Hexahydro-difenidol has a higher affinity for M1 receptors in NB-OK 1 cells, pancreas M3 and striatum M4 receptors (pKi 7.9 to 8.3) than for cardiac M2 receptors (pKi 7.0). (S)-Hexahydro-difenidol, by contrast, is nonselective (pKi 5.8 to 6.1). Our goal in the present study was to evaluate the importance of the hydrophobic phenyl, and cyclohexyl rings of hexahydro-difenidol for the stereoselectivity and receptor selectivity of hexahydro-difenidol binding to the four muscarinic receptors. Our results indicated that replacement of the phenyl ring of hexahydro-difenidol by a cyclohexyl group (----dicyclidol) and of the cyclohexyl ring by a phenyl moiety (----difenidol) induced a large (4- to 80 fold) decrease in binding affinity for all muscarinic receptors. Difenidol had a significant preference for M1, M3, and M4 over M2 receptors; dicyclidol, by contrast, had a greater affinity for M1 and M4 than for M2 and M3 receptors. The binding free energy decrease due to replacement of the phenyl and the cyclohexyl groups of (R)-hexahydro-difenidol by, respectively, a cyclohexyl and a phenyl moiety was almost additive in the case of M4 (striatum) binding sites. In the case of the cardiac M2, pancreatic M3, or NB-OK 1 M1 receptors the respective binding free energies were not completely additive. These results suggest that the four (R)-hexahydro-difenidol "binding moieties" (phenyl, cyclohexyl, hydroxy, and protonated amino group) cannot simultaneously form optimal interactions with the M1, M2, and M3 muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863524 TI - In vitro hydrolysis of RR,SS-threo-methylphenidate by blood esterases- differential and enantioselective interspecies variability. AB - Enantioselective in vitro hydrolysis of methylphenidate (MPH) by the blood esterases of seven mammalian species is reported. The species included rats, rabbits, dogs, cattle, horses, monkeys, and humans. In vitro incubations up to 8 h were carried out in plasma, red blood cells, and whole blood of the various species. Enantioselective differences were evident among the different species on comparison of the data obtained from the three biological fluids. The esterases present in plasma appeared to show greater activity in the hydrolysis of MPH in all species where comparison with the other two biofluids was possible. Only in the case of humans did esterases present in plasma and red blood cells demonstrate opposite enantioselectivity in the hydrolysis of MPH. Thus after 8 h incubation, the RR-MPH/SS-MPH ratios in plasma and red blood cells were 0.31 and 1.16, respectively. PMID- 1863525 TI - Collaborative study on the use of motility enrichment on modified semisolid Rappaport-Vassiliadis medium for the detection of Salmonella from foods. AB - A collaborative study was performed in 15 laboratories to evaluate the use of motility enrichment on modified semisolid Rappaport-Vassiliadis (MSRV) medium for rapid Salmonella detection in a variety of food products. The results of this procedure were compared with those obtained by the cultural procedure using Rappaport-Vassiliadis (RV) broth as selective enrichment and modified brilliant green agar for selective plating. The tests were performed with Salmonella reference samples (SRS) as well as with naturally contaminated food products. When SRS were used without added food the productivity of both MSRV and RV was 96%. When SRS were combined with reference samples containing competitive bacteria the productivity was 98% for MSRV and 95% for RV. In the tests with food samples the productivity of MSRV was 92% with SRS added to food and 96% with naturally contaminated samples, while the productivity of RV was 88% and 90%, respectively. Statistical analysis showed that there was no significant difference between the procedures. PMID- 1863526 TI - DNA hybridization and latex agglutination for detection of heat-labile- and shiga like toxin-producing Escherichia coli in meat. AB - DNA-hybridization and latex-agglutination tests were used for screening of a group of Escherichia coli isolates for heat-labile enterotoxin (LT)- and shiga like toxin (SLT1 or VT1) -producing strains, respectively. Strains tested originated from 162 meat samples (poultry, pigs and beef) chosen at random. Additionally LT- and SLT1-producing reference strains were tested. The DNA hybridization technique allowed screening of large numbers of strains, whereas large scale testing of strains by latex agglutination was laborious. Of 800 E. coli strains tested by DNA hybridization none contained the gene encoding LT. Production of LT as tested by latex agglutination was not found. The gene encoding SLT1 was detected in 10 of the 800 isolates tested. None of these strains, however, showed cytotoxicity on Vero cells. Serotyping was done with sorbitol-negative E. coli strains, first by using the latex-agglutination test for O157 followed by complete serotyping. No E. coli of serogroup O157 were found. Therefore the results obtained also indicate that routine screening of E. coli isolated randomly from food for toxin production is not useful and should be limited to food-borne disease outbreaks with an etiology resembling an E. coli infection. PMID- 1863527 TI - Rates of detection of Salmonella and Campylobacter in meats in response to the sample size and the infection level of each species. AB - Pork, beef and chicken meat samples were collected from slaughter houses, poultry processing plants and meat shops. Rates of incidence of Salmonella spp., Campylobacter jejuni and C. coli with respect to the sample size were compared and the most probable number for these species were determined. Salmonella spp. were detected in 69 (24.1%) of 286 chicken meat samples, in three (3.2%) of 94 pork samples, and in one (1.9%) of 52 beef samples. With chicken meat, the rates of detection were: 19.9% in 25-g, 15.7% in 10-g, and 12.2% in 1-g samples. The populations in most probable numbers, that gave positive results in 31 (20.8%) of 149 samples, ranged from 30 to 10(4) per 100 g, the majority (93.5%) being between 30 and 10(3) per 100 g. C. jejuni and C. coli were detected in 106 (67.9%) of 156 chicken meat samples, in two (2.1%) of 94 pork samples, and none of 52 beef samples. The results obtained with different sample sizes of chicken were compared. Positive rates were 55.8%, 39.7%, 27.6% in 10 g, 1 g, and 0.1 g, respectively. The most probable numbers in 107 (68.6%) positives out of 156 chicken samples examined ranged from 30 to 10(6) per 100 g: 46 (29.5%) contained between 10(2) and 10(3) per 100 g, 22 (14.1%) between 10(3) and 10(4) per 100 g, and the other 19 samples (12.2%) between 10(4) and 10(5) per 100 g. PMID- 1863528 TI - Effect of surface sterilization, fumigation and gamma irradiation on the microflora and germination of barley seeds. AB - Sodium hypochlorite (NaOCl) and mercuric chloride (HgCl2) surface sterilization, methyl bromide and propylene oxide fumigation and gamma irradiation treatments were compared for their effectiveness in killing microorganisms on or within barley seeds. Surface sterilization with 12.5, 25 or 50% (v/v) NaOCl for 5, 15 or 30 min, decreased Fusarium spp., Epicoccum purpurascens, and Bacillus spp. but did not kill Alternaria alternata. However, surface sterilization with 0.1 or 0.2% (w/v) HgCl2 for 3 min significantly decreased A. alternata, Fusarium spp. and E. purpurascens but Bacillus spp. were only killed by 0.3% (w/v) HgCl2 used for 10 min, which also decreased seed germination. Aspergillus flavus inoculated onto barley seeds as spores, was completely killed by surface sterilization with NaOCl but not with HgCl2, while Fusarium culmorum was killed by both NaOCl and HgCl2 treatments. Fumigation with methyl bromide yielding a concentration-time product of 3000 mg h l-1 or with propylene oxide giving a concentration-time product of 2400 mg h l-1 eliminated all filamentous fungi but Bacillus spp. and yeasts survived, and both treatments adversely affected seed germination. Gamma irradiation at a dose of 4 kGy eliminated most Alternaria, Fusarium and Epicoccum spp. but a dose of 12 kGy was required to kill Bacillus spp., yeasts and Aureobasidium pullulans. Germination was improved slightly up to a dose of 8 kGy but gradually decreased with increase in dosage to 15 kGy of gamma irradiation. PMID- 1863529 TI - Rahnella aquatilis, a potential contaminant in lager beer breweries. AB - The species Rahnella aquatilis has been isolated mostly from water, soil, and, in a few cases, from human clinical specimens; little is known about its ecological role. The application of polyacrylamide gel electrophoresis of soluble proteins, DNA-DNA hybridizations and API 20 E systems has shown that Rahnella aquatilis might also be encountered as a contaminant in lager beer breweries. PMID- 1863530 TI - The microbiological quality of drinking water supplies of Izmir City: the incidence of Yersinia enterocolitica. AB - A total of 100 water samples collected from piped public supplies, wells with and without motor pumps, springs and commercially bottled spring waters were microbiologically examined. In order to determine microbiological quality, aerobic bacterial and coliform counts were estimated and the presence of Escherichia coli and Yersinia enterocolitica was investigated. Of the samples tested, 85 of them met the specifications set by TFR (Turkish Food Regulation) for coliforms, whereas 72 of them met the specifications for aerobic bacteria. The number of samples containing Y. enterocolitica and E. coli were found to be 6 and 5, respectively. PMID- 1863531 TI - Inhibitory and stimulatory effects of cumin, oregano and their essential oils on growth and acid production of Lactobacillus plantarum and Leuconostoc mesenteroides. AB - Cumin at concentrations of 0.5, 1.0 and 2.0% (w/w) stimulated growth and acid production of Lactobacillus plantarum and Leuconostoc mesenteroides in a liquid medium. Essential oil from cumin at high concentrations (300 and 600 ppm) inhibited growth and acid production of Lactobacillus plantarum. After a certain period, growth of Leuconostoc mesenteroides was observed at all concentrations (150, 300 and 600 ppm) and its acid production was stimulated at 600 ppm. Oregano and its essential oil at all concentrations inhibited growth of both cultures. Acid production by Lactobacillus plantarum was stimulated by oregano spice. PMID- 1863532 TI - Magnesium inhibits the harmful effects on plants of some toxic elements. AB - Cadmium and aluminium ions - especially in acid soils - are taken up by plants which then become poisoned by them. As a result the roots of the plants become deformed, and the green parts become chlorotic and underdeveloped. The yield will thus be sharply reduced. Culture fluid and culture pot experiments have shown that the toxic effects can be inhibited by magnesium. Investigations have proved that the inhibition is competitive and is based on the antagonism of cadmium and aluminium towards magnesium. Toxic cadmium and aluminium concentrations in the soil can be decreased by the use of non-acidifying fertilizers, and inhibited or prevented with fertilizers containing magnesium, eg Agronit (28% N and 2.5% Mg) or Kardonit (28% N and 5.5% Mg) (Borsod Chemical Works). Cadmium and aluminium taken up by plants are equally detrimental to animal and human organisms through the nutrition chain. For example cadmium may cause sterility, while aluminium may be implicated in Alzheimer's and Parkinson's disease. Magnesium moderates the effects of these two toxic elements in the human organism as well as in plants. PMID- 1863533 TI - Comparative study of effects of magnesium and taurine on electrical parameters of natural and artificial membranes. VIII. Effect on the ultrastructure of human amniotic epithelial cells. AB - The ultrastructure of human amniotic epithelial cells from normal pregnancies, at term, was studied using transmission electron microscopy. The results were analysed by a stereological method which indicates the ratio between the volume of the intercellular space (R1, the microvilli (R2), and the podocytes (R3) versus the cell volume. At low concentration (2 mM), MgCl2 decreased R1 and R3 and had no significant effect on R2. In contrast, taurine (2 mM) increased R1 and had no significant effect on R2 and R3. There is no vicarious action between Mg and taurine. These data are in contrast to the results obtained after electrophysiological studies, which indicates that the structural targets for Mg and taurine are different from the targets responsible for ionic transfer. PMID- 1863534 TI - Serum and intracellular electrolytes in patients with and without pain. AB - The effect of acute stress, with and without pain, on serum and mononuclear cell cation content was studied in 205 healthy women in their last trimester of pregnancy or during normal labour, in patients with acute medical conditions in which pain was or was not present, in acute surgical conditions, and immediately prior to elective surgery. In all subjects there was a fall in serum sodium, potassium, magnesium and calcium concentrations during stress, with an apparent shift into the intracellular space. An inverse correlation was present between the severity of pain and the fall in serum cations. PMID- 1863535 TI - Transient cerebral ischaemic attacks and calcium-magnesium imbalance: clinical and paraclinical findings in 106 patients under 50 years of age. AB - One hundred and six selected patients (71 women, 35 men) suffering from transient cerebral ischaemic attacks (TIA) when aged less than 50 years received a comprehensive diagnostic assessment. Patients were classified into three subgroups, into which 9% could be assigned in approximately equal proportions. These were group A; TIA patients with tetanic syndrome (median age of first TIA 32 years, mainly female, 3.2 attacks per year and changing vascular area); group B; TIA patients with migraine (median age of first TIA 26 years, no predominance of male or female sex, 2.0 attacks per year and mostly in the same vascular area); group C: TIA patients suffering from premature arteriosclerosis (median age of first TIA 40 years, no predominance of male or female sex. 0.8 attacks per year and mostly in the same vascular area). Magnesium (P less than 0.001) and calcium (P less than 0.05) in plasma were reduced in group A, and magnesium (P less than 0.05) in group B, versus group C. The increased propensity to vasoconstriction appears to be an important pathogenic factor, particularly in group A, but also in group B. PMID- 1863536 TI - Long term effects of peak strenuous effort on serum magnesium, lipids, and blood sugar in apparently healthy young men. AB - Earlier findings showed a sustained lowering of serum magnesium concentration (S Mg) which indicated the presence of Mg deficit, and a parallel, delayed rise of blood sugar and serum lipids as a sequel to strenuous effort. S-Mg was still significantly decreased 3 months after termination of peak effort. To gain further perspective, we followed the biochemical sequels of exertion over an extended period of observation, while maintaining the same experimental conditions used earlier, which mimicked those employed in the training of military recruits. We examined two groups of military recruits, n = 15 (group 1), n = 16 (group 2), mean age 18.6, SD 1.3 and 18.7, SD 0.6, years respectively, who underwent a graded training programme of 7 months' duration culminating in a 120 km forced march. Blood was sampled for estimation of S-Mg in 20 soldiers on recruitment, 6 and 10 months after the 120 km march in group 1, and 9, 11 and 15 months after the march in group 2. Blood sugar and serum lipids were screened on recruitment and up to 11 months after the 120 km march. A significant lowering of mean S-Mg was found as late as 10 months after completion of the march in group 1, and 11 months in group 2 (P less than 0.01). Mean serum cholesterol and triglycerides showed a delayed rise, especially in group 2 (P less than 0.05 and P less than 0.001, respectively), whereas blood sugar decreased in group 1, but increased in group 2 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863537 TI - New clinical and experimental aspects of intestinal magnesium transport. AB - Mg transport across various segments of the rat small and large bowel was measured in the absence of electrochemical gradients and using the voltage clamp technique. In the mucosa-to-serosa (ms) Mg flux across the duodenum, ileum, and colon a cellular part is involved, amounting to 40-70% of the total ms Mg flux measured across the short-circuited tissue. However, serosa-to-mucosa (sm) Mg flux is purely passive, suggesting that net Mg transport is largely determined by convectively driven Mg flux across the paracellular pathway. Mg is absorbed across the colon and ileum but in the duodenum paracellularly it is secreted due to an 'anomalous solvent drag effect'. Mg in the caecum decreases cellular ms Ca transport but in the other segments only passive ms Ca flux is reduced by a decrease of the paracellular permeability for Ca, or by a Mg-induced decrease in water absorption. Mg transport across all segments is insensitive to 1,25(OH)2D3. Dexamethasone abolishes cellular Ca transport but stimulates paracellular ms Mg flux in the duodenum. It is concluded that in the rat (a) Mg and Ca are transported by distinct cellular and paracellular mechanisms; (b) Mg transport is largely confined to the paracellular pathway; (c) the ileum and the colon are the major sites for the gut regulation of Mg homeostasis. PMID- 1863538 TI - A history of pediatric hematology/oncology in Canada. AB - In summary, the history of hematology/oncology in Canada is a varied one. Beginning in 1945 in hematology, it has gradually expanded to include oncology. The growth of this specialty has provided a high standard of medical care and free services to afflicted children and their families. A substantial amount of basic and clinical research is carried out in this field. A great deal of work remains to be done in Canada, as elsewhere, if the needs of all patients are to be met and the diseases afflicting them are to be adequately studied. PMID- 1863539 TI - Error in medication. PMID- 1863540 TI - Inflammatory pseudotumor of the lung in children. AB - Two children with inflammatory pseudotumor (IPT) of the lung are reported. Symptomless "cystic" lesions were present on routine chest x ray. Morphological study of these peculiar lesions included light microscopic, immunohistochemical, and ultrastructural analysis. Histologic appearance of the lesion varied from the features of granulation tissue on the periphery to bundles of spindle-shaped cells in the central area. Immunohistochemical findings had no diagnostic value but were helpful in excluding other tumors. Ultrastructural analysis confirmed the mixed cellular composition and benign nature of the lesion. Etiopathogenesis of this process is unknown. IPT can be differentiated from similar lesions and must not be mistaken for malignant tumor. Proper treatment by complete surgical removal of the lesion usually cures the patient. PMID- 1863541 TI - Rhabdomyosarcoma with primary osteolytic lesions simulating non-Hodgkin's lymphoma. AB - We report the case of an 8-year-old child presenting with the pathological fracture of two vertebral bodies due to bone lytic lesions. Physical and instrumental examinations did not show any further evidence of disease. However, bone marrow aspirate showed an infiltrate of poorly differentiated cells. When the child was transferred to the Department of Pediatrics, lymphoblastic leukemia was suspected. Although the morphology of the bone marrow biopsy could have suggested a lymphoblastic lymphoma, further immunochemical and immunological studies together with the study of tissue surface antigens resulted in a diagnosis of embryonal rhabdomyosarcoma with an unusual presentation. PMID- 1863542 TI - Overdose of vinblastine in a child with Langerhans' cell histiocytosis: toxicity and salvage therapy. AB - The therapeutic index of antineoplastic agents is generally low, therefore, errors in administration can cause severe, life-threatening toxicity. The publication of cases of overdoses may provide useful information on the causes of the mistakes, on drug-induced toxic effects, and on salvage therapy. We report a case of vinblastine overdose in a child affected by Langerhans' cell histiocytosis, Hand-Schuller-Christian syndrome according with the previous classification of histiocytosis X. To our knowledge this is the highest dose of vinblastine ever administered. The child was given salvage therapy with steroids and citrovorum factor. Major side effects were neurologic toxicity (seizures, coma) and marrow aplasia, which improved and gradually resolved beginning day 12. PMID- 1863543 TI - Vincristine overdose: experience with 3 patients. AB - Vincristine overdose (7.5 mg/m2) was accidentally administered to 3 children with acute lymphoblastic leukemia. Treatment included double-volume exchange transfusion, phenobarbital administered prophylactically, and folinic acid rescue 18 mg every 3 hours for 16 doses. Vincristine levels were also assayed and showed a dramatic decline in postexchange levels in the 2 patients who survived and an almost unchanged value in the patient who succumbed. Early signs of toxicity in the 2 survivors were peripheral neuropathy (day 4), bone marrow toxicity (day 5), gastrointestinal toxicity (days 6 and 7), and hypertension (days 7 and 8). Marrow aplasia lasted for 4 and 10 days, peripheral neuropathy for 15 and 42 days, gastrointestinal toxicity for 3 and 5 days, and hypertension for 5 and 14 days. The 2 children were discharged on days 13 and 16 and cytostatic therapy was restarted on days 18 and 25. Both are alive without evidence of leukemia. The third patient developed liver and marrow toxicity on day 3 and died on day 9. Postmortem examination showed leukemia infiltration of the liver and spleen. PMID- 1863544 TI - Dactinomycin potentiation of radiation pneumonitis: a forgotten interaction. AB - No mention of dactinomycin potentiation of pulmonary radiation was found in a review of the literature of the past 12 years. Before that, this complication was well described and investigators had calculated that dactinomycin increased the toxic effect of lung radiation by a factor of 1.3 and reduced the radiation tolerance of the lung by at least 20%. An example of such a toxic effect is described in the treatment of a 7-year-old girl with lung metastases from Ewing's sarcoma. The chemotherapy protocol followed contained cyclophosphamide, vincristine, dactinomycin, adriamycin, cisplatinum, VP16, and radiotherapy. The treatment was associated with fatal pulmonary fibrosis following the reintroduction of dactinomycin after radiotherapy. Our experience suggests that there is clinical significance to this complication in sarcoma therapy when dactinomycin-containing protocols are used with radiation in the treatment of pulmonary metastases. PMID- 1863545 TI - Acceleration of leukocyte recovery by administration of short-course high-dose methylprednisolone in children with acute lymphoblastic leukemia. PMID- 1863546 TI - History of pediatric oncology. AB - Pediatric oncology emerged as a subspeciality in the United States of America following the observations in 1948 of Farber and his associates of the benefits of chemotherapy for acute leukemia. The establishment of national cooperative chemotherapy groups furthered its development. More recently, the subspeciality has been recognized by the American Board of Pediatrics. Even more recently, training programs for the subspecialty have been given accreditation. Parallel to development of the specialty in the United States has been a similar evolution of pediatric oncology in Europe. PMID- 1863547 TI - Mass screening for neuroblastoma in Japan. AB - The present status of the neuroblastoma mass screening program in Japan, the first national trial in the world, is evaluated. This program, now in its fifth year, was conducted in cooperation with the infants' mothers, local health centers, screening centers, and selected hospitals. From the onset of the program in Kyoto in 1973 to the end of 1989, 337 cases were detected and analyzed. Most cases were detected at early stages and 97% are expected to be cured. Several social, technical, and clinical problems remain unresolved. PMID- 1863548 TI - Writing easily read patient education handouts: a computerized approach. AB - A patient education handout is a potentially powerful tool for communicating information to patients. Patients will derive the greatest benefit from what they can easily read and understand. This article describes the use of computerized readability formulas in writing patient education handouts. Suggestions are offered for writing such handouts are illustrated. PMID- 1863549 TI - Word processing in the physician's office. AB - Although word processing has become an accepted business function for many office professionals, physicians have been slow to recognize the many uses that it has to offer. The physician's office can achieve greater productivity and efficiency by the integration of word processing into both the clerical and clinical sectors of medical practice. The task begins with an organization of professional communications and is developed based on the needs of an individual practice. PMID- 1863550 TI - Making your own videotapes for patient instruction. AB - Producing your own videotapes can be both fun and clinically helpful. They are extremely effective for patient instruction and for obtaining informed consent. This article discusses the production, presentation, and effective use of videotapes in office practice. PMID- 1863551 TI - Producing a dermatology newsletter. AB - The marketing concepts, benefits and drawbacks, topics, and basic elements of a Dermatology practice newsletter are discussed in this article. The methods and production mechanics for such a newsletter are then presented. PMID- 1863552 TI - To battle the disease, is to know the enemy. AB - Patient education is absolutely vital to the treatment of psoriasis. It increases the patient's sense of control and enhances a positive working relationship with medical professionals. PMID- 1863553 TI - Patient education. PMID- 1863554 TI - The use of printed instruction sheets to enhance patient compliance. AB - Printed instruction sheets can improve doctor/patient relationships. Patients can better understand physician requirements and treatment regimens when instructions are preprinted or written. Information sheets increase patient compliance and decrease malpractice claims. PMID- 1863555 TI - Preparation and mechanics of patient instruction sheets. AB - Patient instruction sheets are simple and economical to prepare. They increase patient compliance, produce improved treatment results and patient satisfaction, and save the physician considerable time. PMID- 1863556 TI - Strategies for using patient instruction sheets. AB - Patient instruction sheets are a patient pleasing practice tool, especially if used creatively before seeing patients, to augment telephone conversations, and to detail postoperative care. Customizing, availability, and other strategies for optimal use of patient instruction sheets are discussed. Although patient instruction sheets are significant time savers, their updating, customizing, and effective use requires a small investment of physician time and effort. PMID- 1863557 TI - Bone morphogenetic protein 4 (BMP-4), a member of the TGF-beta family, in early embryos of Xenopus laevis: analysis of mesoderm inducing activity. AB - We have screened a Xenopus ovary cDNA library using a synthetic oligonucleotide derived from that part of the inhibin beta A sequence, which is highly conserved within the TGF-beta family. Out of several clones yielding autoradiographic signals four turned out to represent Xenopus counterparts to the human bone morphogenetic protein 4 (BMP-4). Each two of the four sequences are nearly identical and probably account for different alleles whereas the two pairs showing 5% divergence may have arisen by genome duplication in this tetraploid species. The amino acid sequence of the Xenopus protein is 80% homologous to the human sequence showing no single exchange within the last 100 amino acids at the C-terminus. This region, which constitutes the main part of the mature, biologically active protein, also exhibits substantial homologies to other representatives of the TGF-beta family, especially to the Drosophila DPPC protein. Transfection of COS-1 cells with the Xenopus BMP-4 sequence under control of the CMV-promoter leads to the secretion of a protein which exhibits mesoderm inducing activity when tested with animal cap explants from Xenopus blastula stage embryos. PMID- 1863558 TI - Early development of leg and wing primordia in the Drosophila embryo. AB - The development of the leg and wing primordia in the Drosophila embryo has been traced using molecular markers. Distal-less and disconnected gene expression provide molecular labels for the leg primordia throughout embryonic development, disconnected expression in the developing leg primordia depends on Distal-less activity. The leg primordia arise as discrete clusters of cells that occupy well defined positions in the embryonic ectoderm. At later stages of embryogenesis the primordia become morphologically recognizable and are intimately associated with the development of the Keilin's organs. The presumptive leg disc and the Keilin's organ appear to derive from a common primordium. Similarly the Abnormal leg pattern gene provides a molecular label for the wing and haltere primordia. The dorsal thoracic primordia appear to be of independent origin from the legs. PMID- 1863559 TI - Fluorescent image cytometry: from qualitative to quantitative measurements. AB - Image analysis is being increasingly used in biology and medicine; however, in order to obtain truly quantitative data and thus avoid errors in interpretation, a certain number of precautions must be taken when the image is digitized, well before any attempt is made to analyse or interpret the data. This is particularly true for image microfluorometry. In this article we will examine an image analysis system for fluorescent images composed of a mercury lamp, a microscope, a high sensitivity video camera and an image analyser and evaluate the principal sources of random and non-random errors, various constraints, and their relative importance. A signal correction protocol is proposed to minimize non-random errors during digitalization. A few examples are given to illustrate its efficiency. PMID- 1863560 TI - Need for morphometric analysis in grading bladder tumours. PMID- 1863561 TI - Selected bibliography. PMID- 1863562 TI - Anatomy of the orbital septum and associated eyelid connective tissues. Implications for ptosis surgery. AB - The anatomy of the orbital septum and associated eyelid connective tissues was examined using cadaver dissection, histologic sections, surgical observations, and special radiologic imaging. The embryologic development of the eyelid connective tissues was also reviewed. Examination revealed a distinct layer of fibroadipose tissue in the eyelid and eyebrow posterior to the orbicularis and frontalis muscles, and anterior to the orbital septum. Fibrous septa within the submuscular fibroadipose tissue become contiguous with more compact lamellae of the orbital septum posteriorly imparting a multilayered quality to the orbital septum. Fat within the fibroadipose layer anterior to the orbital septum may be mistaken for the preaponeurotic fat pad by the unwary surgeon and may lead to surgical error. The orbital septum and the levator aponeurosis were found to join 2 to 5 mm above the superior tarsal border (average, 3.4 mm). Recommendations for ptosis surgery based on these anatomic principles are given. PMID- 1863563 TI - Further modifications of the Muller's muscle-conjunctival resection procedure for blepharoptosis. AB - A modified Muller's muscle-conjunctival resection procedure was performed to correct minimal to mild blepharoptosis with good levator function. A semilinear formula was used to excise specific amounts of Muller's muscle for different amounts of blepharoptosis. This formula was modified by less than adequate responses with the phenylephrine test. The phenylephrine test was also used to unmask contralateral ptosis so that bilateral surgery or less resection on the primarily ptotic eye could be planned. This modified technique and formula provides an approach to better quantitate minimal to mild ptosis surgery and yield more predictable results. PMID- 1863564 TI - Combined procedure for repair of involutional entropion. AB - Combined procedures that address multiple etiologic factors in involutional entropion are not new, but ophthalmic surgeons have been slow to accept this surgical approach. Traditional procedures that correct only one or two of the etiologic factors have a high incidence of recurrent entropion. The purpose of this article is to encourage the use of a combined procedure in the treatment of all cases of primary and recurrent entropion to minimize recurrences. Between 1983 and 1989, 127 consecutive eyelids with involutional entropion in 97 patients were operated by the senior author (R.P.C.) using the procedure described in this paper. Of these eyelids, 39% (49) had previous surgery and 22% (28) had more than one previous procedure. Although occasional minor postoperative problems occurred, they were readily managed, and there have been no known recurrences of entropion with an average follow-up of 33 months. PMID- 1863565 TI - Dacryocystorhinostomy use of a "coffee can lid" stent. AB - Many techniques have been described for performing successful dacryocystorhinostomies (DCRs). The patency of the passageway from the internal common punctum through the osteotomy site into the nasal cavity is usually the limiting factor in the success of the DCR. We present a modification using a "coffee can lid" stent to keep the osteotomy site open when there is no free space between the osteotomy and the nasal septum (medial wall of the nose). PMID- 1863566 TI - Eyelid lipogranuloma after hydraulic oil injury. AB - The cytopathology of a lipogranuloma of external origin is reported in the eyelid of a 32-year-old man excised 1 year following regional exposure to an explosion of hydraulic oil under high pressure. The foreign lipids were still present in chronic lipogranulomas with intercellular lipid-filled cysts surrounded by macrophages and giant cells containing intracellular lipid-filled vacuoles. These indicate efforts in storage and very slow digestion. Secondary fibrosis in the region of the lipogranuloma was an important associated process. In view of the widespread technical use of hydraulic oily fluids under high pressure, it is recommended that these fluids be biodegradable. PMID- 1863567 TI - Cyanoacrylate-assisted trial eyelid repositioning for epiphora. AB - Cyanoacrylate skin adhesions of the lateral lower eyelid reinforced with surgical tape were created in three patients in order to temporarily correct epiphora due to lid laxity, eyelid malposition, punctal malposition or punctum-eyelid apposition. The cyanoacrylate adhesions resulted in relief of epiphora or aided in establishing the cause of epiphora, and allowed the patient to "sample" the anticipated benefits of corrective lid surgery. Trial eyelid repositioning may be useful in cases where there is only mild or equivocal punctal malposition or lid laxity and the surgeon wishes to predict the effect of corrective lid surgery. PMID- 1863568 TI - Transient internal ophthalmoplegia during blepharoplasty. A report of three cases. AB - The present paper presents three cases of transient internal ophthalmoplegia during blepharoplasty. All cases were characterized by a dilated pupil that was unreactive to light or an accommodative stimulus. There were no cases of visual loss or permanent pupillary abnormalities. We attribute the temporary pupillary mydriasis and accommodative insufficiency to anesthesia of the short ciliary nerves or ciliary ganglion from local anesthetic diffusing into the orbit at the time of injection. To the best of our knowledge this is a complication of eyelid surgery that has not been previously described. PMID- 1863569 TI - A micro system for rigid bony fixation in orbital surgery. AB - Plates and screws are effective for rigid internal fixation of bone fractures and osteotomies in the midface, orbit, and cranium. We describe our experience with the Luhr Micro System. This is the newest generation of Luhr Systems and is the smallest system available for rigid internal fixation. The self-tapping screws are 0.8 mm in diameter, with lengths of 2-8 mm. The plates have an extremely flat profile. We have used the Micro System for closure of elective osteotomies following resection of orbital neoplasm, bony orbital reconstruction, and repair of congenital craniofacial deformities. Because the orbital bones have minimal functional stress, the Micro System provides adequate support. The plates are not apparent through the thin periorbital skin. For bony fixation in the periorbital region, the Micro System appears superior to larger systems and to wire or nonabsorbable sutures. PMID- 1863570 TI - Orbital roof "blow-in" fractures. AB - Seven patients with significant frontal trauma involving the supraorbital region associated with orbital roof "blow-in" fractures were admitted to the Maryland Institute for Emergency Medical Services Systems (MIEMSS) at the University of Maryland Medical System over a 16-month period. High-resolution computed tomography (HRCT) with three-dimensional reconstructions demonstrated a downward displacement of the orbital roof in the absence of any orbital rim discontinuity. Associated findings included contussive and hemorrhagic injury to the ipsilateral frontal and parietal lobes, proptosis, ptosis, chemosis, orbital hematoma, and optic nerve contusion. The only long-term ocular pathology in this group of patients was mild to severe optic atrophy. It is recommended that all patients with frontal bone trauma have thin-cut computed tomographic evaluation of the orbit. PMID- 1863571 TI - Orbital exenteration. The reconstructive ladder. AB - Following orbital exenteration, there is a spectrum of immediate and delayed options for orbital reconstruction. Goals of reconstruction after exenteration include detection of recurrent disease, restoration of boundaries between the orbit and surrounding structures, and optimal aesthetics. Local solutions to problems of the exenterated orbit, such as healing by granulation or application of split-thickness skin grafts, are advantageous for detecting recurrent disease. Regional solutions, involving transfer of periorbital tissue into the orbit, may mask recurrent disease and create adjacent deformity; however, these solutions can be used to restore orbital boundaries and shallow the orbital cavity. Distant solutions, such as skin-muscle flaps and free tissue grafts, allow for facial reconstruction in patients with extensive orbital and periorbital defects. PMID- 1863572 TI - Reanimation of the paretic eyelid using gold weight implantation. A new approach and prospective evaluation. AB - Sixty-one lid-loading procedure, performed by the author, were evaluated prospectively. Simple, gold weight implantation, combined with lower lid retractor recession, placement of fascia lata, and lateral tarsal strip tightening is effective for promoting voluntary closure and correction of lower lid paralytic ectropion. Placement of a heavier gold weight, in combination with mullerectomy, is a reliable new approach for mimicking involuntary blink without ptosis. PMID- 1863573 TI - Study on antithrombogenicity of poly[beta-(acetylsalicylyloxy)ethyl methacrylate] relative to poly(hydroxyethyl methacrylate). AB - The antithrombogenicity of a polymer made of aspirin bound to hydroxyethyl methacrylate (HEMA), abbreviated as ASA-polymer, was compared with that of poly(hydroxyethyl methacrylate) (PHEMA). Platelet from platelet rich plasma (PRP) incubated with ASA-polymer surface exhibited noticeable decreases in adhesion and aggregation as compared to platelets incubated with PHEMA. Low molecular weight components other than aspirin, which may be released from ASA-polymer during the incubation with PRP, or contact with ASA-polymer causing denaturation of platelets without morphological changes could be responsible for the decrease of adhesion and aggregation. Both PRP and PPP exposed to ASA-polymer-coated surfaces exhibited a much smaller partial thromboplastin time (PTT) than if exposed to PHEMA-coated surfaces; the PTT of ASA-polymer was similar to that of glass exposed plasma. With respect to the in vivo antithrombogenicity, the ASA-polymer surface led to thrombus formation. This may be due to the partial hydrolysis of the acetyl groups resulting in the formation of a negatively charged surface which in turn accelerates the coagulation cascade despite its inhibitory effects on platelet adhesion and aggregation. On the other hand, neointima formed around a thrombus layer on PHEMA-coated sutures after 14 days. PMID- 1863574 TI - A new in vitro thrombogenicity test for medical tubes. AB - Basic information on the affected coagulation behaviour of healthy human blood passing foreign artificial surfaces is of immense importance for a safe clinical therapy. An in vitro screening method is presented which tests the thrombogenicity of medical tubes, applying the clinically already established resonance thrombography (RTG). Several medical tubes with various types and contents of plasticizers are tested and compared with materials free of additives. The effect of the release of ingredients is indicated by this procedures, as well as the influence of a sterilizing treatment with gamma radiation on the physical surface properties, such as smoothness. In all cases, the modified RTG method proves its suitability and sensitivity. In addition, this method allows accurate adjustment of the extrusion parameters for tube manufacturers. PMID- 1863575 TI - Interactions of functionalized polystyrene derivatives with the complement system in human serum. AB - The interactions between blood and insoluble polysaccharidic surfaces result in activation of the immune system of complement. When substituted with carboxymethyl groups, Sephadex loses its capacity to activate complement, whereas Sephadex sulphate has been described as an activator. In order to elucidate the molecular mechanisms of complement activation and inhibition, a simpler polymer model has been chosen: it consists of an insoluble polystyrene backbone on which either isolated hydroxymethyl or sulphonate groups or both are present. The surfaces bearing the isolated groups consume complement but the mechanisms involved are quite different. In contrast, a surface bearing equal proportions of both types of groups is a non-activator. Such model surfaces can be very useful for designing artificial surfaces able to control in situ complement activation. PMID- 1863576 TI - Influence of molecular structure on the synergistic action of theophylline or dipyridamole derivatives in the prostaglandin-type inhibition of platelet aggregation. AB - Approximately 30 new derivatives of theophylline and dipyridamole have been prepared and examined as potentiators of the inhibition of platelet aggregation induced by the prostaglandin analogue BW 245C. Potentiating activity has been found to be sensitive to molecular size and also to the presence of specific groups. Polymeric adducts based on dextran, poly(ethylene glycol) or poly(N-vinyl pyrrolidone), and aliphatic esters with alkyl chain-lengths greater than 7 are inactive in potentiation. Derivatives containing carboxyl groups are also inactive. Potentiation is discussed in terms of platelet membrane penetration and extra- and intra-cellular processes. The latter are invoked to account for the enhanced potentiation shown by dipyridamole and derivatives when aggregation is induced by PAF-acether rather than ADP. One derivative of particular interest is the adduct of theophylline with 1,2,5,6-diisopropylidene-D-glucose, containing a furanose ring. This is a more active potentiator than theophylline itself, possibly owing to its molecular resemblance to cAMP. On conversion to the pyranose form all activity is removed. PMID- 1863577 TI - Effect of particle size on phagocytosis of latex particles by guinea-pig polymorphonuclear leucocytes. AB - The effect of the size of foreign particles on phagocytosis by guinea-pig polymorphonuclear leucocytes (PMNs) was investigated using latex particles having approximately the same surface potentials but different sizes. Two types of latexes with different negative surface potentials, those having amino groups (Ami-latexes) and those having carboxylic acid groups (Ca-latexes), were used in this experiment. Since Ca-latexes had different surface potentials for different particle sizes, the carboxylic acid groups were modified by the carbodiimide method to make the surface potentials almost equal. Phagocytosis was estimated by the rate of oxygen consumption. It was found that the phagocytosis reached its maximum when the latex particle size was about 0.5 microns. This finding was plausibly explained by considering the two probabilities that a latex particle comes into contact with a PMN surpassing a potential barrier and the contact takes place at certain receptor areas favourable to phagocytosis on the PMN surface. PMID- 1863578 TI - Selective synthesis of 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine as a protein modifier. AB - 2,4-Bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine, a protein modifier with two polyethylene glycol chains (activated PEG2) was synthesized from monomethoxypolyethylene glycol and cyanuric chloride using zinc oxide as a catalyst by the improved method of a previous study (Matsushima et al., Chem. Lett. 7, 773, 1980). The product was identified as activated PEG2 without contamination of by-products with chromatographic and structural analysis. PMID- 1863579 TI - In vitro evaluation of an epoxy resin's cytocompatibility using cell lines and human differentiated cells. AB - The cytocompatibility of a polyepoxy resin (Elf Aquitaine) has been studied using both cell lines and human differentiated cell cultures. The human models were gingival fibroblasts and bone osteoblasts, while the cell lines were Hela cells and 3T3 Balb/c cells. Basal cytocompatibility was assessed by estimation of the cell proliferation, total cell protein content, cell membrane sub-lysis, and cell attachment and spreading. Specific cytocompatibility concerning human osteoblasts, from both alveolar and trabecular bone, was determined by measuring the intracellular alkaline phosphatase activity. Resin colonization by the cells was studied by both TEM and SEM. The behaviour of the two cell lines reveals a significant level of discrepancy, whereas the behaviour of human cells, whatever the model, is comparable; however, osteoblasts look more sensitive. Moreover, the results show that this epoxy resin exhibits a moderate cytocompatibility which could be the result of the cytotoxicity of early released products, associated with the considerable surface roughness. PMID- 1863580 TI - Public pressure, the congress, and the FDA: the elements of a social catastrophe. PMID- 1863581 TI - Technique of venous catheterization for sequential blood sampling from the pig. AB - A surgical technique for catheter implantation for sequential blood sampling in the pig is described. This methodology minimizes stress to the animal and chances of catheter dislodgement, both of which are detrimental to accurate long-term metabolic assessment of the animal model. The technique involves implantation of a vinyl catheter via the external jugular vein into the vena cava. To ensure catheter retention, the method uses a silicone plug fitted to the catheter and located cranial to its entry to the vein, double ligation at the venous insertion, subsequent passage of the catheter to exit 10 cm cranial to the scapula on the dorsal midline, and a denim vest fitted to the thorax. With this technique seven out of nine catheters have functioned more than 50 days, two functioned for approximately 100 days, and one for over 150 days. PMID- 1863582 TI - In vitro vs in vivo corrosion analyses of two alloys. AB - The in vitro and in vivo corrosion characteristics of two alloys, cast Co-Cr-Mo (ASTM F75) and wrought Ni-Cr-Mo, were evaluated using electro-chemical corrosion analysis. Two in vitro electrolytic solutions were utilized, an isotonic saline solution consisting of 0.9 w/o NaCl in distilled water and an isotonic saline solution with 10 v/o sterile calf serum. The in vivo environment was created by implanting cylindrically shaped specimens of each alloy into the back muscles of New Zealand white rabbits. Cyclic anodic and cathodic polarization curves were generated for the three test conditions and subsequently were compared. Anodic curves conducted using the isotonic saline and isotonic saline plus serum electrolyte solutions were very similar to the anodic curves generated for the implanted alloy specimens for both alloys. The corrosion rates predicted from the in vitro and in vivo cathodic polarization curves were not statistically different for the three test conditions. Overall, the corrosion data generated using the in vitro environmental conditions adequately predicted the in vivo corrosion behavior of the cast Co-Cr-Mo and wrought Ni-Cr-Mo alloys. PMID- 1863583 TI - Feasibility of intraoperative aortic root angiography in the identification of critical coronary lesions. AB - Early revascularization is critical for the treatment of acute myocardial infarction (AMI) because the ischemic myocardium begins to suffer irreversible damage after 4 h from the onset of symptoms. However, to make a diagnosis, perform coronary angiography, and prepare for operative revascularization usually takes longer than 4 h. Also, once a patient develops severe cardiogenic shock, coronary angiography is often impossible. Without angiography, the patient is no longer a candidate for surgical repair. To circumvent this problem, we designed this experiment to determine whether intraoperative aortic root angiography after cardiopulmonary bypass and cardioplegic arrest could satisfactorily substitute for angiographic examination in the identification of critical coronary lesions. The feasibility of this approach was tested in dog hearts in which one or tow of the major coronary arteries were ligated. The ascending aorta was then clamped, contrast material was injected, and continuous real-time fluoroscopic images were obtained and recorded on videotape. The videotape was then analyzed by three physicians independently, each without prior knowledge of the lesion locations. Lesions of the left anterior descending artery, the circumflex coronary artery, and the right coronary artery were identified with 94, 91, and 94% accuracy, respectively, for an overall identification rate of 92%. We conclude that aortic root angiography reliably demonstrates coronary artery lesions, and refinements in this technique may allow certain patients to undergo coronary operations without preoperative catheterization. PMID- 1863584 TI - Biochemical mechanisms of laser vascular tissue fusion. AB - This study examines the biochemical changes that occur in argon laser-fused canine veins compared with control segments of vein. Laser fusions were formed using 0.5 W argon laser energy (1100-1500 J/cm2). Immediately following tissue fusion, blood flow was reestablished to test the integrity of the welds. 1-mm3 sections of the anastomoses and control sections were minced and protein extraction was performed by solubilizing the tissue in hot SDS Laemmli gel sample buffer. The proteins were separated electrophoretically on 5 and 10% polyacylamide SDS gels and silver stained. The analysis demonstrated significant biochemical differences between control and lased veins. We noted increases in several proteins after laser welding: the putative beta chain of type V collagen (5/5 gels), the putative gamma chain of type I collagen (4/5 gels), a 156-kDa protein (based on collagen molecular weight standards) 7/7 gels), an 82-kDa protein (8/9 gels), and several proteins of lower molecular weight (3/8 gels). The increases may be due to crosslinking of lower molecular weight proteins, degradation of higher molecular weight proteins, or increased solubility of certain proteins. These findings suggest that laser welding may occur by formation of crosslinks or by denaturation and reannealment of structural proteins. PMID- 1863585 TI - Effect of Ringer's lactate irrigation on the formation of postoperative abdominal adhesions. AB - Intraabdominal adhesions continue to pose a potentially serious postoperative clinical problem. Reported here is an experiment designed to study any effect that balanced Ringer's lactate (RL) solution may have on intraabdominal adhesion formation. Surgical trauma was induced in mice by controlled gauze abrasion of one side of the abdominal wall; the opposite side was used as a control. RL irrigation was compared with no irrigation. Adhesions were scored on the basis of incidence (%) and severity (on a 0-10 scale). The abraded right peritoneum exhibited 100% adhesions for both the RL group and the nonirrigated group. However, on the side that was not abraded, the nonirrigated group showed only 30% incidence of adhesions and 1.7 +/- 3.3 severity as compared with 100% adhesions and 7.7 +/- 2.2 severity for the RL group. These results suggest the need for further studies to establish the extent to which irrigation with solutions such as Ringer's lactate or saline may enhance formation of postoperative adhesions. PMID- 1863586 TI - Porcine model for vascular graft studies. AB - Models for the study of prosthetic vascular graft infection have been studied frequently in the dog and rabbit. We have developed a reproducible swine model to study this problem and its treatment. The cardiovascular system, healing characteristics, and the bloodstream clearance of bacteria in swine more closely resembles those of humans than do other animal models. The low cost and availability of the swine is an additional attractive aspect. One hundred fifty six farm-bred pigs have undergone infrarenal aortic replacement with a 3-cm segment of 6-mm prosthetic graft over the past two years. Graft infection was produced by (1) direct inoculation of 10(6) Staphylococcus aureus at the time of the surgery or (2) intravenous infusion of bacteria (10(2)-10(6) organisms/mL) immediately after surgery. All animals were sacrificed 1 to 4 weeks later, depending on the study design. Cultures, histology, and electron microscopy were performed on each graft. Anesthetic complications were rare (2.5%). Postoperative complications leading to animal death decreased with increasing experience (11.5%), but included graft thrombosis, bleeding, sepsis, intussusception, and colonic ischemia. Wound infection was the most common cause of morbidity. The swine model is an attractive alternative to that of other animals for the study of prosthetic vascular graft infections. Further details of the operative technique and the comparison to the human and other animal models is discussed. PMID- 1863587 TI - Species differences in the infectability of vascular grafts. AB - The susceptibility of different species to bacteremia may influence the results of studies on vascular graft infection. The present study compares prosthetic graft infection in canine and porcine models. Thirty-four mongrel dogs and 38 Yorkshire pigs underwent replacement of the infrarenal aorta with a 3-cm segment of a woven Dacron prosthesis. At the time of closure, each animal received an intravenous inoculum of 10(2) to 10(8) Staphylococcus aureus (S. aureus). Graft cultures at 1 week produced a predictable infection rate in dogs, while pigs developed only random infections (dogs: 23/34; pigs: 7/38; p = .0001). The median infective dose (ID50) in dogs was 10(2.9) but pigs did not develop enough infections to determine this value. Electron microscopy revealed a smooth fibrin surface in grafts explanted from pigs, while grafts from dogs demonstrated bacteria enmeshed in an irregular fibrinous lining. Prosthetic vascular grafts in dogs are more susceptible to hematogenous infection than those in pigs. Because hematogenous infection in humans is a rare event, the swine model may be a more appropriate representation of the clinical situation. PMID- 1863588 TI - Species differences in the clearance of Staphylococcus aureus bacteremia. AB - Studies on vascular graft infections may be influenced by species differences in bacteria clearance. The present study compares the bloodstream elimination of Staphylococcus aureus (S. aureus) in dogs and pigs. Four mongrel dogs and four Yorkshire pigs received a 20-min infusion of 10(6) S. aureus labeled with indium 131. Through a catheter placed in the infrarenal aorta, blood samples were removed at intervals for 5 h after infusion. The liver, spleen, and lungs were biopsied at 5 h. Blood and tissue samples were then counted in a gamma counter. The calculated phagocytotic index, k, for dogs was 8.6 X 10(-4), while for pigs it was 1.5 X 10(-3), indicating significantly faster bacterial clearance in pigs (p = .009). After 2 1/2 h, significantly fewer counts were present in pigs at most time points (p less than .05). Organ counts indicated higher counts in the dog liver and spleen and in the lungs of pigs (p less than .0001). This study indicates that S. aureus bacteremia is cleared faster by pigs, primarily by the lungs, compared to dogs, in which liver-spleen clearance predominated. These differences should be considered when the results of graft infection studies are compared. PMID- 1863589 TI - Improved xenograft survival with continuous infusion deoxyspergualin and RATG. AB - The critical shortage of available donor organs is the major limit to current allogeneic transplantation. Xenografting has the potential to overcome this difficult problem. Suppressing the vigorous rejection response remains a major obstacle to the clinical application of xenografting, 15-Deoxyspergualin (DOSP), a potent new immunosuppressive agent has been shown to be effective in allogeneic and xenogeneic experimental models. This study tests DOSP in combination with rabbit antithymocyte globulin (RATG) in the hamster-to-rat cardiac xenograft. Results show that combination therapy with DOSP/RATG was superior to treatment with either agent alone (p less than .05). Optimal graft prolongation (20.9 days versus control of 3.1 days, p less than .05) was achieved with combination therapy of RATG and DOSP 2.5 mg/kg day-1 by continuous infusion. PMID- 1863590 TI - Simple method of determining pulmonary blood flow in the anesthetized rat. AB - We have developed a simple, accurate, and relatively inexpensive method of measuring pulmonary blood flow in the anesthetized rat using a modification of the dye dilution technique. The method is attractive because it allows for the measurement of pulmonary blood flow and also the determination of pulmonary substrate flux. Using rats with a catheter in the carotid artery and a doubly cannulated right ventricle (RV), a constant infusion of [14C]P-aminohippurate ([14C]PAH) is begun via the distal RV catheter. After steady state is obtained the infusion of [14C]PAH is then stopped and blood is immediately withdrawn from the proximal RV cannula. This maneuver insures that [14C]PAH from the infusate is not sampled through the proximal RV catheter. Obtaining the blood from the proximal RV catheter within 5 s after clearing the infusion catheter insures that no dilution of [14C]PAH in the right ventricle (from recirculating blood) occurs. Catheter position is verified at autopsy. Calculations are performed to determine pulmonary blood flow. In 20 normal rats studied, the pulmonary blood flow was 24 +/- 1 mL/100 g body wt min-1 and in 12 endotoxin-treated rats (10 mg/kg body wt) the pulmonary blood flow was 32 +/- 2 mL/100 g body wt. These values are similar to values obtained with other methods used to measure total pulmonary blood flow. PMID- 1863591 TI - Indirect measurement of systolic blood pressure in the rabbit. AB - Long-term studies of rabbit blood pressure require a reliable method for repeated blood pressure measurements. Ideally, this method would be simple, noninvasive, and accurate over the range of anticipated blood pressures. To facilitate our own studies of rabbit carotid artery graft patency, we have developed a technique for the indirect measurement of systolic blood pressure in the rabbit that utilizes a photoplethysmograph sensor placed distal to an inflatable air bladder positioned over the central ear artery. We have compared measurements obtained with this method to direct measurements of aortic pressure and found a linear correlation. PMID- 1863592 TI - Comparison of functional and metabolic assessments in preservation techniques for heart transplantation. AB - The present study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation using metabolic and functional assessments. In both groups the hearts were initially protected with iso-osmolar potassium Tyers' cardioplegia. The donor hearts of group A were placed in simple hypothermic storage for 5 h. The donor hearts of group B were placed onto a perfusion apparatus for 5 h with perfusion pressure maintained at 28 cm of H2O and a myocardial temperature of 8-10 degrees C. The perfustate consisted of Tyers' solution with the addition of 2 mg/L of mannitol, 12.5 mg/L of glucose, 5 units/L of insulin, and 95% oxygen. The ischemic interval within both groups was 6 h, including orthotoipic transplantation. Investigation was conducted at three time periods: prepreservation (T1) in the donor, and postpreservation (T2) and immediately after loading (T3) in the recipient. Following volume loading for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than .05; stroke index, p less than .05) with no significant change in systemic vascular resistance, systemic blood pressure, and heart rate. There was also significant improvement in myocardial performance (p less than .05) for the hypothermic perfusion group following volume loading. Results of fatty acid turnover using 15-p-iodo (123I)-phenylpentodecanoic acid indicate significantly greater increase in metabolic rate for the perfusion group than for the hypothermic storage group. (p less than .05). This indicates improved metabolic status of the heart treated with the hypothermic perfusion technique. We conclude that a combination of functional and metabolic assessments is a good method for deduction of ischemic-reperfusion injury. We also conclude that hypothermic perfusion is superior to hypothermic storage for in vitro preservation of hearts for heart transplantation. PMID- 1863593 TI - Differential effects of fatty acids on glycolysis and glycogen metabolism in vascular smooth muscle. AB - The effects of fatty acids of different chain lengths on aerobic glycolysis, lactic acid production, glycogen metabolism and contractile function of vascular smooth muscle were investigated. Porcine carotid artery segments were treated with 50 microM iodoacetate and perchloric acid tissue extracts were then analyzed by 31P-NMR spectroscopy to observe the accumulation of phosphorylated glycolytic intermediates so that the activity of the Embden-Myerhof pathway could be tracked under various experimental paradigms. Aerobic glycolysis and lactate production in resting arteries were almost completely inhibited with 0.5 mM octanoate, partially inhibited with 0.5 mM acetate and unaffected by 0.5 mM palmitate. Inhibition of glycolysis by octanoate was not attributable to inhibition of glucose uptake or glucose phosphorylation. Basal glycogen synthesis was unchanged with palmitate and acetate, but was inhibited by 52% with octanoate incubation. The characteristic glycogenolysis which occurs upon isometric contraction with 80 mM KCl in the absence of fatty acid in the medium was not demonstrable in the presence of any of the fatty acids tested. Glycogen sparing was also demonstrable in norepinephrine contractions with octanoate and acetate, but not with palmitate. Additionally, norepinephrine-stimulated isometric contraction was associated with enhanced synthesis of glycogen amounting to 6-times the basal rate in medium containing octanoate. Contractile responses to norepinephrine were attenuated by 20% in media containing fatty acids. Thus, fatty acids significantly alter metabolism and contractility of vascular smooth muscle. Fatty acids of different chain lengths affect smooth muscle differentially; the pattern of substrate utilization during contraction depends on the contractile agonist and the fatty acid present in the medium. PMID- 1863594 TI - Cellular daunomycin fluorescence in multidrug resistant 2780AD cells and its relation to cellular drug localisation. AB - Multidrug resistant (MDR) 2780AD human ovarian carcinoma cells were loaded with the fluorescent anticancer agent daunomycin (DN). Fluorescence anisotropy was lower than for corresponding A2780 wild-type cells, indicating that DN was less rigidly bound than in the wild-type cells. Average fluorescence quenching of DN was lower for 2780AD cells. Data were fitted into a model with a highly quenched fraction (fraction A), corresponding to DN intercalated in DNA, and an unquenched fraction (fraction B). The ratio A/B was one order of magnitude lower for the MDR cells than for the wild-type cells. Two other MDR cell lines were investigated and low A/B ratios were found in both cases. Thus, evidence has been provided that in MDR cells the DNA-bound fraction is relatively low and that more free DN is present, for example in acidic vesicles. PMID- 1863595 TI - Effects of glutathione depletion on the synthesis of proteoglycan and collagen in cultured chondrocytes. AB - We studied the effect of the depletion of glutathione on the synthesis of proteoglycan and collagen in cultured chick chondrocytes. When the cultured chondrocytes were incubated with 1 mM buthionine sulfoximine (BSO), a specific inhibitor of gamma-glutamyl-cysteine synthetase, the intracellular glutathione level markedly dropped within 12 h with no loss of cell viability. Incorporation of 35SO2-4 into proteoglycan was lowered in the presence of BSO. When the 35S labeled proteoglycans were separated into two fractions by glycerol density gradient centrifugation, the inhibitory effect of BSO on the synthesis of proteoglycan was greater in the fast-sedimenting proteoglycan fraction, which consisted mainly of cartilage specific large proteoglycan (PG-H), than in the slowly sedimenting proteoglycan fraction. The inhibition by BSO of the synthesis of core protein-free glycosaminoglycan chains primed by p-nitrophenyl-beta-D xyloside was smaller than the inhibition of the synthesis of proteoglycan. Analysis of glycosaminoglycans labeled with [3H]glucosamine indicated that the treatment of chondrocytes with BSO resulted in a small increase in the proportion of synthesis of hyaluronic acid to the synthesis of total glycosaminoglycan. The incorporation of [3H]proline into collagen was also inhibited by BSO. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the 3H-labeled collagen showed that, in the presence of BSO, processing of Type II collagen appeared to slow down and the proportion of Type X collagen synthesis was reduced. PMID- 1863596 TI - Local deformation of human red blood cells in high frequency electric field. AB - A method of local and general deformation of single erythrocytes by external forces in high-frequency electric field is described. The method allows the avoidance of any mechanical contact of the cell with electrodes. Under the action of the forces applied human erythrocytes change their shape and produce various membrane structures: long filopodia-like processes, retraction fibers and lamella like structures. These structures are never formed by erythrocytes under normal conditions, but are typical for fibroblasts, macrophages and epithelium cells. By the method developed the elastic properties of spicules on the membranes of echinocytes were also studied. Deformation of echinocyte in high-frequency electric field leads to the smoothing out of spicules. However, after the electric field is turned off, echinocyte restores its initial forms including the number and localization of all initial spicules on the cell surface. PMID- 1863597 TI - Cell cycle control by calcium and calmodulin in Saccharomyces cerevisiae. PMID- 1863598 TI - Molecular species analysis of 1,2-diacylglycerols and phosphatidic acid formed during bombesin stimulation of Swiss 3T3 cells. AB - Swiss 3T3 cells were labelled with [3H]glycerol and stimulated with bombesin over a time course of 20 min. The individual 1,2-diacylglycerols produced were quantified by acetylation followed by analysis by HPLC and argentation chromatography. The major phospholipids and phosphatidic acid were acetolysed and then analysed in the same manner. The data show that even at an early time of stimulation (30 s), stimulated diacylglycerol formation comes from at least two sources--phosphoinositides and phosphatidylcholine. PMID- 1863599 TI - Illumination increases the phosphorylation state of maize leaf phosphoenolpyruvate carboxylase by causing an increase in the activity of a protein kinase. AB - Illumination of maize leaves increases the phosphorylation state of phosphoenolpyruvate carboxylase and reduces the sensitivity of the enzyme to feedback inhibition by malate. Red, white and blue light were each found to be equally potent, and the effect of light was blocked by 3(3,4-dichlorophenyl)-1,1 dimethylurea. A phosphoenolpyruvate carboxylase kinase was partially purified from illuminated maize leaves by a three-step procedure. Phosphorylation of phosphoenolpyruvate carboxylase by this protein kinase reached 0.7-0.8 molecules/subunit and correlated with a 3- to 4-fold increase in Ki for malate. The protein kinase was inhibited by L-malate, but was insensitive to a number of other potential regulators. Freshly prepared and desalted extracts of darkened maize leaves contained very little kinase activity, but the activity appeared when leaves were illuminated for 30-60 min before extraction. The catalytic subunit of protein phosphatase 2A from rabbit skeletal muscle, but not that of protein phosphatase 1, could dephosphorylate phosphoenolpyruvate carboxylase. The protein phosphatases 1 and 2A activities of maize leaves were not affected by illumination. It is suggested that the major means by which light stimulates the phosphorylation of phosphoenolpyruvate carboxylase is by an increase in the activity of the protein kinase. PMID- 1863600 TI - Characterization of proteoglycans synthesized by rabbit articular chondrocytes in response to transforming growth factor-beta (TGF-beta). AB - The effect of transforming growth factor-beta (TGF-beta, 1 ng/ml) on proteoglycan synthesis by rabbit articular chondrocytes in culture was studied in the presence of fetal bovine serum. Exposure of confluent cells for 24 h to the factor resulted in a marked increase of 35S-labeled sulfate incorporation in the newly synthesized proteoglycans (PG), as estimated by glycosaminoglycan (GAG) radioactivity (+58%). The onset was observed 6 h after addition of the factor but was significant after 12 h. TGF-beta also enhanced the uptake of [35S]sulfate by chondrocytes, but had no effect on the release of PG by these cells. The effect of TGF-beta on the distribution of PG between the medium and the cell layer was shown to be dependent on the serum concentration in the medium: the relative proportion of cell-layer associated GAG of TGF-beta-treated cells decreased with increasing concentration of fetal bovine serum. The proportion of aggregated PG, the hydrodynamic size of PG monomers and GAG chains were not modified by TGF beta, but the relative distribution of disaccharides 6- and 4-sulfate in GAG chains was altered by the factor: the proportion of chondroitin 6-sulfate (C6S) was decreased while that of chondroitin 4-sulfate (C4S) was augmented in presence of TGF-beta, leading to a decrease of the ratio C6S/C4S (-11 to -22%, P less than 0.01). The present study indicates that TGF-beta promotes the synthesis of a modified extracellular matrix in cultured articular chondrocytes. This mechanism could be relevant to some aspects of cartilage repair in osteoarticular diseases. PMID- 1863601 TI - Differential effect of transforming growth factor beta on proteoglycan synthesis in human embryonic lung fibroblasts. AB - The effect of transforming growth factor beta (TGF-beta) on the biosynthesis of individual proteoglycans (PGs) by human embryonic lung fibroblasts has been investigated using specific antibodies and cDNA probes. Human lung fibroblasts secrete the two small chondroitin/dermatan sulfate PGs, PG-I or biglycan (300 kDa) and, in a larger proportion, PG-II or decorin (130 kDa). Metabolic labeling experiments reveal that TGF-beta induces selectively the expression of PG-I, whereas the level of PG-II remains unaltered. The effect of TGF-beta on PG-I and PG-II has been studied by immunoprecipitation and Northern blot analysis. Either at the core protein or mRNA level, a specific 5-fold increase in PG-I can be observed. TGF-beta acts probably at the transcriptional level, as actinomycin D blocks completely the TGF-beta induced proteoglycan synthesis. A low saturation density and a slower growth rate is also observed for TGF-beta treated cells. The possible role of PG-I and PG-II as mediators of the growth inhibition caused by TGF-beta is discussed. PMID- 1863602 TI - Genetic and biochemical analysis of the adenylyl cyclase of Schizosaccharomyces pombe. AB - The adenylyl cyclase gene, cyr1, of Schizosaccharomyces pombe has been cloned. We have begun an analysis of the function and regulation of adenylyl cyclase by disrupting this gene and by over-expressing all or parts of this gene in various strains. cyr1- strains are viable and contain no measurable cyclic AMP. They conjugate and sporulate under conditions that normally inhibit wild-type strains. Strains containing the cyr1 coding sequences transcribed from the strong adh1 promoter contain greatly elevated adenylyl cyclase activity, as measured in vitro, but only modestly elevated cAMP levels. Such strains conjugate and sporulate less frequently than wild-type cells upon nutrient limitation. Strains which carry the wild-type cyr1 gene but that also express high levels of the amino terminal domain of adenylyl cyclase behave much like cyr1-strains, suggesting that the amino terminal domain can bind a positive regulator. A protein that copurifies with the adenylyl cyclase of S. pombe cross-reacts to antiserum raised against the S. cerevisiae adenylyl cyclase-associated regulatory protein, CAP. PMID- 1863604 TI - [Malaria. Quid novi?]. PMID- 1863603 TI - Distinct modulatory effects of bryostatin 1 and staurosporine on the biosynthesis and expression of the HIV receptor protein (CD4) by T cells. AB - A family of structurally related macrocyclic lactones, bryostatins, have recently been shown to display several intriguing pharmacologic properties. Bryostatins are biosynthetic products of bryozoa phyllum of marine animals. To extend the analyses of the biological activities of these highly unusual biosynthetic animal products, we have examined the effect of bryostatin 1 (bryo-1) on the steady state expression of the human immunodeficiency virus receptor, CD4, by normal peripheral blood T lymphocytes. Incubation of the cells with 5 nM bryo-1 caused a substantial loss of CD4 from the cell surface, as analyzed by flow cytometry using anti-CD4 monoclonal antibody. The modulation of CD4 expression by bryo-1 was not due to a cytotoxicity effect: in the culture conditions where it modulated CD4, bryo-1 also stimulated the expression of the interleukin 2 gene, as indicated by northern blot hybridization. In addition, incubation of the lymphocytes with nanomolar amounts of protein kinase C antagonist, staurosporine, resulted in the inhibition of the bryo-1-induced modulation of CD4 expression. The results of radioimmunoprecipitation analysis of detergent lysates of [35S] methionine-labeled lymphocytes strongly suggest that bryo-1 inhibits the glycosylation and expression of CD4 in a manner similar to that of tunicamycin. PMID- 1863605 TI - [Evaluation of 2 culture systems for the isolation of opportunistic mycobacteria]. AB - The increment of infections produced by opportunist environmental mycobacteria (OEM) raises the question about the appropriateness of the conventional culture methods since they were initially designed to isolate M. tuberculosis. In this study we have comparatively evaluated the yield of a conventional culture (Lowenstein-Jensen) with respect to that of Middlebrook 7H12 (Bactec) in 396 selected samples in which OEM were isolated. Samples with commensal flora were previously subjected to a chemical homogenization-decontamination process with alkaline N-acetyl-cysteine. All cultures were sown with standard inoculates obtained from centrifugate material. The 7H12 culture showed a more rapid detection (mean: 17-18 days) and a greater effectiveness in the isolation of eventually pathogenic mycobacteria than the conventional Lowenstein-Jensen culture. The 7H12/LJ ratio for the species with high clinical relevance was: 1.3 for M. kansasii, 1.0 for M. marinum, 1.8 for M. scrofulaceum, 1.3 for M. xenopi, 1.5 for M. avium-intracellulare, 0.5 for M. chelonae, and 2.0 for M. fortuitum. PMID- 1863606 TI - [Abscess of the psoas: a not-so-rare entity. Analysis of a series of 18 cases]. AB - We have studied 18 patients with abscess at the psoas who had a mean age of 43.55 +/- 18.9 years and a predominance of males (77.8%). In nine cases the abscess was secondary to a lumbar discal spondylitis, in 5 cases to a sacroiliitis, in one case to abdominal disorder, and 3 cases the abscess was considered of a primary origin. The etiologic agents were S. aureus (8 cases), E. granulosus (5 cases), M. tuberculosis (3 cases), and B. melitensis (1 case). In one patient the infective agent was not isolated and in two cases the abscesses were infected by E. granulosus and P. aeruginosa. The clinical picture on admission was studied in all cases. Microbiological and pathologic analysis of the abscess allowed to establish the diagnosis in 11 cases (yield: 84.6%). Computerized axial tomography was the most useful imaging technique. Antimicrobial treatment was undertaken in 16 cases. Four patients recovered with pharmacological treatment alone. Surgical treatment was performed in 13 cases. Aspirative punction/drainage was carried in only one patient. The clinical course was favourable in 16 patients (88.9%). Our data indicate that the incidence of abscess of the psoas in cases of intraabdominal infections is low. In our series the incidence of abscesses secondary to hydatidosis is relatively high. PMID- 1863607 TI - [Evaluation of bronchoalveolar lavage in the microbiological diagnosis of pneumonia in patients at risk]. AB - Bronchoalveolar washout was performed in 130 patients with pneumonia during a period of 28 months. Microbiological investigation involved common bacteria, Legionella, fungi, viruses (Cytomegalovirus, herpes, RSV), Mycobacterium, and Pneumocystis carinii. Infection HIV was present in 75% of patients. The remaining patients had malignant diseases or severe pneumonia. The overall sensitivity of the technique was 65.4% and the positive predictive value was 92%. The technique was less sensitive in cases of bacterial pneumonia (sensitivity = 34.4%). This was attributed to the fact that 82.8% of these cases received antibiotic therapy. Pneumocystis carinii and Mycobacterium tuberculosis were the most common agents (44.8% and 34.5%, respectively). In seven instances the clinical picture was related to cytomegalovirus, although this diagnosis can not be easily done. PMID- 1863608 TI - [Bacteremia after fibrobronchoscopy. Prospective study]. AB - We prospectively evaluated in 88 inpatients the incidence of fever and bacteremia after fiberoptic bronchoscopy and its predisposing variables. Fever was present in 27% of cases and no bacteremia could be demonstrated neither associated nor intercurrent . Chronic Hepatic Disease, endobronchial pathology and bronchial biopsy practice were predisposing factors for fever development in the univariant analysis. PMID- 1863609 TI - [Evaluation of a new method for urine screening based on the study of catalase]. AB - A new method of urine screening based on the enzymatic study of catalase (Uriscreen) was evaluated. Catalase is produced by the majority of microorganisms that cause urinary infections as well as by red cells, uroepithelial cells and PMN. In 553 consecutive urine samples we studied the sediment, the conventional culture, and the Uriscreen test. Comparative study between culture and Uriscreen revealed a sensitivity of 92.3%, specificity of 83.3%, negative predictive value of 96.2%, and positive predictive value of 69.9%. In 86% of the samples the results obtained with both techniques were similar, whereas in 14% of the cases they failed to coincide. Among the 74 cases of disagreement, 12 were false negative (culture positive, Uriscreen negative) and 62 were false positive (culture negative, Uriscreen positive). The high sensitivity and negative predictive values obtained with the screening method indicate that this is an useful procedure for the study of negative urines since it allows to rapidly classify 60.2% of the samples. PMID- 1863610 TI - [Cutaneous lesion after handling animals]. PMID- 1863611 TI - [Tuberculosis of the pubic bone]. PMID- 1863612 TI - [Bursitis of the trochanter caused by S. typhi]. PMID- 1863613 TI - [Infection of a neoplastic ovarian cyst caused by Salmonella enterica subspecies enterica, serotype Enteritidis]. PMID- 1863614 TI - [Polymicrobial bacteremia caused by E. gergoviae and C. albicans]. PMID- 1863616 TI - [Nosocomial infections caused by Staphylococcus aureus resistant to methicillin. A challenge for infection control]. PMID- 1863615 TI - [Hepatic abscess caused by Streptococcus uberis]. PMID- 1863617 TI - [Sensitivity of anaerobic bacteria: when and how]. PMID- 1863618 TI - [Epidemic outbreak of methicillin-resistant Staphylococcus aureus in a general hospital. Preliminary report]. AB - The incidence of MRSA infections in Spain had remained in a low level through the years, being MRSA usually less than 1.5% of all S. aureus isolates. Since October 1988, we have detected in our hospital a MRSA outbreak. The epidemic started in the surgical wards, and spread through the rest of the institution. The incidence of cases was higher in the ICU's, areas that act as "multipliers" of the outbreak. In spite of standard control measures, the total number of patients with MRSA was 245 in April 1990. We studied prospectively a sample of 100 MRSA patients: thirty-six percent were colonized and 46% infected. The more common source of infection was the lower respiratory tract and primary bacteremia. The infection-related mortality was 30%. Our MRSA strain belong to phage type III, and shows a characteristic multiple antibiotic resistant pattern, the MRSA strain is sensitive to vancomycin, fusidic acid, phosphomycin and cotrimoxazole. Over the entire outbreak period, the MRSA strain developed resistance to rifampin, imipenem-cilastatin and ciprofloxacin. In spite of all control measures implemented, the outbreak can not have been totally controlled, and MRSA is now an endemic pathogen in our institution. Therefore, major changes in therapeutic approach to nosocomial infections have been since then introduced. PMID- 1863619 TI - [Evaluation of the Mycoscreen technique for the detection and quantification of genital mycoplasmas]. AB - A total of 161 samples from genital sources were evaluated using two different methods for genital Mycoplasma isolation: inoculation to urea broth, arginine broth and A7 solid media (standard method) and a new enzymatic method (Mycoscreen Oxoid). The isolation rates for Ureaplasma urealitycum were 42% (standard method) and 49% (Mycoscreen) (sensitivity: 100%; specificity: 88%). The isolation rates for Mycoplasma hominis were 13% (standard method) and 14% (Mycoscreen) (sensitivity: 80%; specificity: 95%). Using the enzymatic method, manufacturer's positive result is defined as a count greater than 10,000 UCC-ml at 24 hours. When we compare the 24 hours results, the concordance rates was 84% (Ureaplasma urealyticum) and 62% (Mycoplasma hominis). Mycoscreen method is a valid and fast technique for the isolation and identification of genital Mycoplasma. It also allows a fast screening of pathologic counts of Ureaplasma urealyticum in genital exudates. PMID- 1863620 TI - [Evolution of the sensitivity of Bacteroides group fragilis at the Sevilla University Hospital (1983-1987)]. AB - The evolution of antimicrobial susceptibility of Bacteroides fragilis over a five year period is described. We have studied 30 selected strains isolated each year at the University Hospital of Sevilla (total: 150 strains). We did not find any resistant strain to chloramphenicol, metronidazole or imipenem. Resistance to piperacillin (8%) and cefoxitin (13%) remain constant over the study period. Resistance to cefmetazole, cefotaxime, mezlocillin, ofloxacin, clindamycin and moxalactam ranges from 24% to 37%. A rise in the percentage of resistant strains to ticarcillin (from 17% to 30%) and ceftizoxime (from 0% to 40%) was also seen during the study period. Bacteroides thetaiotaomicron was the overall more resistant species, and B. fragilis the more sensitive. PMID- 1863621 TI - [Antimicrobial activity of ornidazole and 6 other antibiotics against anaerobic bacteria]. AB - The antimicrobial susceptibility of 235 anaerobic bacterial strains to ornidazole, metronidazole, chloramphenicol, clindamycin, penicillin, cefoxitin and imipenem has been studied using agar-dilution technique. Ornidazole and metronidazole were active against 88.6% and 86% of gram-positive cocci. Overall, 99.1% of Bacteroides group fragilis, and 91.3% of non-fragilis Bacteroides were also sensitive to both drugs. We did not find any Clostridium perfringens resistant strain. Cefoxitin and penicillin showed good activity against all Clostridium perfringens strains, and also against 97.7% and 92.5% of gram positive cocci. We found one single imipenem resistant strain among gram-positive bacteria. Bacteroides fragilis also showed sensitivity to penicillin (41.5%), cefoxitin (85.7%) and imipenem (97.1%). Clindamycin was active against Clostridium perfringens (90.9%), gram-positive cocci (86.7%) and imipenem (68.6%). Chloramphenicol showed good activity against Clostridium perfringens (100%), gram-positive cocci (95.5%) and Bacteroides spp. (99.4%). Our results showed an overall good activity of all the seven drugs tested against anaerobic gram-positive microorganisms. Of notice, we found a good activity of chloramphenicol, imipenem, metronidazole and ornidazole against Bacteroides spp. PMID- 1863622 TI - [Detection of strains of E. coli producing STa toxin in the feces of patients with diarrhea using a competitive ELISA system]. AB - We evaluate the presence of heat-stable STa toxin producers E. coli strains from stools of patients with acute diarrhoea. As detection method, we used a commercially-available enzyme-linked competitive assay (ELISA). Over a three months period, 279 E. coli strains were analyzed. Only two (0.71%) were STa toxin producers. Both isolates are from pediatric cases (2 and 4 years of age), without any epidemiologic relationship between them. Therefore, we conclude that this infection could be considered as a non-epidemic community-acquired diarrhoeal disease. PMID- 1863623 TI - [Deep infections of the sternal wound following heart surgery: postoperative mediastinitis]. PMID- 1863624 TI - [Serology of hydatidosis]. PMID- 1863625 TI - [Psychomotor retardation, convulsions and pneumonia]. PMID- 1863626 TI - [Erythematous nodule on the hand]. PMID- 1863627 TI - [Acute hematogenous osteomyelitis caused by Eikenella corrodens]. PMID- 1863628 TI - [Bacteremia caused by Vibrio cholerae non-01]. PMID- 1863629 TI - [Sepsis caused by Achromobacter xylosoxidans]. PMID- 1863630 TI - [Fulminating purpura and staphylococcal sepsis]. PMID- 1863631 TI - [Evaluation of a new reagent for anti-rubella IgG]. PMID- 1863632 TI - [Encephalitis caused by rubella in an adult patient]. PMID- 1863633 TI - [Myopericarditis associated with pneumonia caused by Mycoplasma pneumoniae]. PMID- 1863634 TI - [Hemolysis secondary to acute brucellosis]. PMID- 1863635 TI - [Etiology of otitis externa in the city of Cadiz]. PMID- 1863636 TI - Cautious optimism. PMID- 1863637 TI - The metamorphosis of gene insertion and gene therapy. PMID- 1863638 TI - Evaluation of relative promoter strength in primary hepatocytes using optimized lipofection. AB - For most genetic deficiencies manifested in the liver, maximization of gene expression in hepatocytes will be an important factor in achieving successful gene therapy. A rapid, highly efficient, and nontoxic method for transfecting DNA into hepatocytes was used to compare directly promoter strengths of various cellular and viral promoters. Conditions are described here for transfecting 5 10% of primary hepatocytes using the positively charged liposomes, Lipofectin. Cells are not damaged by this method as they continue to transcribe genes controlled by liver specific promoters and can survive for over 2 weeks in culture. We find that the cytomegalovirus, SR alpha, and beta-actin promoters are more active than the SV40, RSV, RNA polymerase II, albumin, alpha 1-antitrypsin, or phosphoenolpyruvate carboxykinase promoters. A simple TK promoter and a TK promoter with the polyoma enhancer (MCI) were almost completely inactive. This information will be useful in the construction of vectors designed to express genes efficiently in primary hepatocytes for purposes of gene therapy, although the stability of expression from these promoters will need to be demonstrated in hepatocytes in vivo. PMID- 1863639 TI - Safety issues related to retroviral-mediated gene transfer in humans. AB - The first three approved human clinical trials utilizing retroviral-mediated gene transfer are now underway. While this technology holds great promise for the study and treatment of human disease, it also poses a number of safety concerns. In evaluating clinical protocols, potential complications and the likelihood of their occurrence are estimated by review committees so that a risk/benefit assessment can be made. Current knowledge, reviewed in this article, suggests that no acute complications secondary to retroviral-mediated gene transfer are likely, but the possibility of long-term or unforeseen sequelae in patients suggests the need for post-treatment monitoring. PMID- 1863640 TI - Activation of a diphtheria toxin A gene by expression of human immunodeficiency virus-1 Tat and Rev proteins in transfected cells. AB - Expression of a gene encoding the diphtheria toxin A (DT-A) fragment, controlled by tissue specific regulatory elements, has previously been used to kill selected cell populations. Here, we have examined the feasibility of controlling DT-A expression using regulatory systems from the human immunodeficiency virus (HIV-1) genome. Plasmids were constructed which express either DT-A or, as a model system, the luciferase (luc) reporter gene, under control of HIV-1 long terminal repeat (LTR) sequences (-167 to +80). While trans-activation by expression of the viral protein Tat was demonstrated, significant basal expression was observed. To reduce basal expression, cis-acting negative regulatory elements from the env region of the HIV-1 genome were inserted in the 3' untranslated region of both the luc and DT-A constructs. This dramatically reduced basal expression from the HIV LTR, and now both viral regulatory proteins Tat and Rev were required for maximal trans-activation. Such regulation of DT-A expression might be therapeutically applied to selectively kill HIV-infected cells in acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). PMID- 1863641 TI - Retroviral vectors related to the myeloproliferative sarcoma virus allow efficient expression in hematopoietic stem and precursor cell lines, but retroviral infection is reduced in more primitive cells. AB - Retroviral vectors are considered to be the most suited vehicles for somatic gene therapy with hematopoietic stem cells as targets. Retrovirus-mediated gene transfer into differentiation-restricted hematopoietic precursor (FDC-P1, FDC-P2) and multipotent progenitor (stem) cell lines (FDC-Pmix) is inefficient. Two cellular restrictions are involved. One is specific for stem but not precursor cells and is at the level of transcription. Due to a unique property of the transcriptional control region of the myeloproliferative sarcoma virus (MPSV), vectors derived from MPSV are not affected by this block. The second restriction occurs before proviral DNA synthesis and integration. This inhibition of effective viral infection depends on the state of differentiation, being more pronounced in multipotent clonogenic blast cells. This block to retroviral infection affects all retroviral vectors tested. PMID- 1863642 TI - Ethical manipulations: an ethical evaluation of the debate surrounding genetic engineering. AB - "Manipulation" per se is not bad. The crucial question in the moral debate about genetic engineering is: When and how are we allowed to manipulate? Unfortunately, the moral discussion surrounding this question is itself being manipulated. There are moral manipulations (by those who wish to either reassure or to alarm) and there are ethical manipulations (the failed utilitarian calculus and the centering of the discussion only around rules, rights, and duties). A different ethical approach is needed: one based on virtues. The duty of ethics is to help us understand the moral possibilities in each situation, i.e., to develop our moral sensibility. In the area of genetic engineering research we are motivated by a will to know, but at the same time we fear total self knowledge. We want to control, to improve our world and ourselves, but we recoil at obtaining ultimate perfection. Therefore, we must value the unknowable, the uncontrollable. Our everincreasing capacity to mould the world and ourselves is making it more difficult to develop a sensitivity for what is given and cannot be made. It is dangerous for our ethics to assume the activistic traits of our technology. We risk losing a fundamental element of what we are, or ought to be. We should train ourselves in moral passivity. PMID- 1863643 TI - Clinical considerations in the design of protocols for somatic gene therapy. AB - Despite two decades of investigating the potential for somatic gene therapy in curing human disease, few clinical trials are being proposed. This delay is due in part to limitations of existing methods for gene transfer and to the recognized need to proceed judiciously into this controversial arena. Delay is also caused by a disjunction between the traditional precedents and principles of clinical investigation and the procedures instituted to regulate somatic gene therapy. The premise of this report is twofold: first, that more extensive clinical investigation of gene transfer technologies would be beneficial to patients, medicine, and basic science and second, that clinical investigations could be expedited by appealing to the established experience in clinical investigation without compromising the scientific excellence and discipline essential for this highly public process. This report develops a clinical perspective on potential applications of existing gene transfer technologies and the issues involved in developing experimental protocols. The initiation of clinical trials should be a primary goal of gene therapy research programs. PMID- 1863644 TI - Zidovudine in asymptomatic HIV infection: knowledge and uncertainty. PMID- 1863645 TI - Tuberculosis in HIV infection. PMID- 1863646 TI - Human immunodeficiency virus-associated granuloma annulare. PMID- 1863647 TI - Evidence of HTLV-I infection in Singapore prostitutes. AB - Sera obtained in 1987 from 63 male and 632 female Singapore prostitutes were screened for antibody to human T-cell leukaemia virus (HTLV)-I with a particle agglutination test. Of the 3 males and 4 females who were positive one had antibody to HTLV-I core and envelope antigen on Western Blot. Two subjects had presumptive antibody to HTLV-I core antigen and a third subject had such antibody on a repeat specimen in 1989. These sera were negative for HIV-1 antibody. There is evidence of infection with HTLV-I or a variant virus in this population. The infection is likely to have been sexually transmitted. PMID- 1863648 TI - Chlamydia test monitoring during therapy. AB - Forty-eight women with chlamydial cervicitis were followed with chlamydial culture and antigen tests (immunofluorescence and enzyme immunoassays) during the course of therapy to study the rate of disappearance of viable organisms and chlamydial antigen. On treatment day 2, two-thirds of the patients were positive by one or more of the tests while 81% were negative by all tests on day 4. All screening methods used had turned negative on the 6th day of therapy. The antigens were found to persist somewhat longer than viable organisms. This persistance should, however, be of no clinical significance. PMID- 1863649 TI - Rape and HIV. AB - The risk of contracting HIV infection as a result of rape is unknown. We describe 4 female patients who were found to have antibodies to HIV-1 following rape, only one of whom had another recognized risk factor for HIV infection. The need for careful follow-up of rape victims, and the potential for HIV acquisition by the assailant is discussed. PMID- 1863650 TI - Sexually transmitted diseases in HIV-1 seropositive women at presentation. AB - Ninety women who were HIV antibody positive attended the genitourinary medicine clinics of East Riverside up to May 1990. Seventy-five of these women (83%) were examined for co-existent sexually transmitted disease (STD) at presentation. The prevalence of STD in these women was compared to the incidence of STD in all females attending in 1989. Syphilis and chlamydia were found to be significantly more common in women with HIV infection. We feel that a full examination for STD is an important aspect in the management of these women. PMID- 1863651 TI - Prepucial occlusion and circumcision after genital herpes infection. PMID- 1863652 TI - Anal and laryngeal papillomata in an 8-month-old child. PMID- 1863653 TI - Feigned HIV disease. PMID- 1863654 TI - Domiciliary nebulized pentamidine prophylaxis. PMID- 1863655 TI - Aetiology of non-gonococcal urethritis. PMID- 1863656 TI - STDs and rape. PMID- 1863657 TI - AIDS literature index. PMID- 1863658 TI - A learning network model of the neural integrator of the oculomotor system. AB - Certain premotor neurons of the oculomotor system fire at a rate proportional to desired eye velocity. Their output is integrated by a network of neurons to supply an eye position command to the motoneurons of the extraocular muscles. This network, known as the neural integrator, is calibrated during infancy and then maintained through development and trauma with remarkable precision. We have modeled this system with a self-organizing neural network that learns to integrate vestibular velocity commands to generate appropriate eye movements. It learns by using current eye movement on any given trial to calculate the amount of retinal image slip and this is used as the error signal. The synaptic weights are then changed using a straight-forward algorithm that is independent of the network configuration and does not necessitate backwards propagation of information. Minimization of the error in this fashion causes the network to develop multiple positive feedback loops that enable it to integrate a push-pull signal without integrating the background rate on which it rides. The network is also capable of recovering from various lesions and of generating more complicated signals to simulate induced post-saccadic drift and compensation for eye muscle mechanics. PMID- 1863659 TI - Dynamic theory of action-perception patterns: the "moving room" paradigm. AB - Action-perception patterns are studied theoretically in terms of equations of motion that capture the coordination capacity of the nervous system. We consider intrinsic dynamics in the absence of visual information that contain a single posture state as a fixed point attractor. We couple these intrinsic dynamics to visual information that stabilizes posture in the visual world. This leads to a theory of postural sway induced by an optic flow field ("moving room" paradigm). The optic flow is parametrized in a simplest approximation by the expansion rate of a relevant perceptual target. We show how temporal stability as the key concept of this theory can lead to prediction and serve as a measure of perceptual coupling. Finally, we discuss the relation of the present theory to biological cybernetics. PMID- 1863660 TI - Multifrequency behavioral patterns and the phase attractive circle map. AB - With relative phase as a collective variable or order parameter, phase attractive dynamics can capture the temporally coherent behavior of a large number of different experimental systems. We present results from multifrequency coordination experiments in humans showing: a) that phase attraction persists especially for low order frequency ratios; b) that short-term jumps from one phase relation to another occur within a frequency ratio; c) that the most stable frequency-ratios are low order; and d) that transitions frequently occur from higher order (e.g. 5:2, 4:3) to lower order (2:1, 1:1) frequency ratios. We study a modified sine circle map with built-in phase attractive dynamics that qualitatively accounts for these results. In this phase-attractive map, patterns arise from competition between external driving and intrinsic phase attractive dynamics. The relative strength of extrinsic and intrinsic parameters determines the width of Arnol'd tongues, thereby influencing the delay or acceleration of irregular behavior. Behavioral complexity is inversely proportional to tongue width, thus accounting for the relative difficulty of performing different multifrequency behaviors and why "errors" in such behavior are often seen to occur. PMID- 1863661 TI - Simulated bipolar cells in fovea of human retina. I. Computer simulation. AB - This static bipolar cell (BC) model of the human fovea is based on a number of reasonable assumptions. The human fovea is directly responsible for visual acuity and color vision. The fovea can be considered as having two parts; a central fovea with only red- and green-sensitive cones and a parafovea with blue sensitive cones added to the other two. A cone mosaic can be precisely organized spatially into unit hexagons that specify inputs to horizontal cells (HC) and BCs. The retina up to and including BCs is piece-wise linear, i.e. at a given steady-state adapting light intensity BC outputs are linear functions of the physical image. BC centers receive inputs directly from weighted cones, while antagonistic surrounds receive inverted inputs from HCs. Appropriate optical and chromatic filtering due to the eye that are taken from human data are incorporated into the model. Chromatic aberrations are simulated by three separate point spread functions that also are taken from human data. Automatic gain control of cones is a function of intensity and wavelength of the steady adapting light. PMID- 1863662 TI - Simulated bipolar cells in fovea of human retina. II. Spectral responses of bipolar cells. AB - The static model developed in Part I is used to study spectral responses of C type bipolar cells (BC). Once unique loci are adjusted to their proper wavelengths, and with a specified set of absorption spectra for cones, spectral responses of C-type BCs are dependent on only the balance between BC receptive field center and surround responses. This is true regardless of cone mosaic or BC receptive field organization. The unique yellow loci for the r-g channel is set at 576.7 nm while the unique green locus for the blue-center BC is set at 517.7 nm. A unique orange locus for a combined r-g and bl-y channels is set at 600 nm by multiplying the blue-center BC response spectra by a factor of six before adding to the r-g channel. PMID- 1863663 TI - The glomerular filtration barrier of the kidney in seven vertebrates classes. Comparative morphological and histochemical observations. AB - In the mammalian kidney, the glomerular filtration barrier (GFB) is mostly composed of endothelial and epithelial cells with the glomerular basement membrane interposed. In lower vertebrates, extensive regions of the GFB consist of the endothelial and epithelial cells, each lying on its own basement membrane. These two basement membranes border the mesangium, which contains mesangial cells (surrounded by its own discontinuous basement membrane), microfibrils and collagens (cross-striated fibrils, anchoring fibrils, and 5 nm interfibrillar filaments). Occurrence and extension of these mesangial components decrease from fish to mammals. Anionic binding sites associated with the different structures of the GFB of all animal species have been demonstrated by using dyes such as Alcian blue (with or without addition of electrolytes), Ruthenium red or Safranine O. The surface coat of endothelial and epithelial cells, the laminae rarae (interna and externa) of the glomerular basement membrane, the laminae rara and diffusa (wherever distinct endothelial and epithelial basement membranes occurred) as well as the collagen fibrils show particles (with polycationic dyes) or filaments (with monocationic dyes). The mesangial microfibrils are usually well preserved and intensively stained. PMID- 1863664 TI - Cellular localization of dihydrofolate reductase-thymidylate synthase in carrot cells. AB - The intracellular distribution and localization of dihydrofolate reductase thymidylate synthase of wild type suspension carrot cells was analysed using cytochemical and immunocytochemical techniques; in both resting and growing normal cells (E4) the activity appeared to be predominantly cytoplasmic. The pattern of localization of the enzyme was also analysed during the different phases of the cell cycle. To this end carrot cells were synchronized with aphidicolin (an inhibitor of the alpha-like DNA polymerase which blocks cells at the G1/S boundary) and cycle phases checked by labelled-thymidine incorporation. Protoplasts obtained from cells inhibited with aphidicolin or from cells sampled at different times after the removal of the drug (S and G2 phase), failed to show a nuclear localization of DHFR-TS. These results indicate that in carrot the bifunctional enzyme does not change compartment during the cell cycle. Surprisingly Mtx-resistant cells (E2A2, E2A1C6; overproducing DHFR-TS) showed, irrespective of their physiological state (quiescent or growing), also a relevant nuclear or perinuclear immunofluorescence which could not be detected using cytochemical techniques. The reason of this altered localization is not clear and its possible relation with altered cytophysiological parameters is discussed. PMID- 1863665 TI - Cell kinetics and DNA content (ploidy) of human skin under expansion. AB - One question which still remains unanswered concerning expansion of human skin is whether expansion simply stretches the skin or whether it induces a real neo production of epithelium. To evaluate the proliferative activity of the human skin before and after expansion, we performed an autoradiographic study and a densitometric analysis on sections of skin biopsy from 11 patients. The results of the cellular kinetic study showed that expansion induces an increase in the epidermal proliferative activity. On the contrary, the densitometric analysis did not show a parallel increase of the proliferating cells after expansion. This discrepancy is discussed in terms of the modified morphology of the tissue. The proliferative activity of skin in the back region increases more than in that of the neck. Preliminary results have shown that the proliferative activity increases with time of expansion in days. The presence of a low percentage of cells with altered DNA content indicates, at least over the short term, the absence of dysplastic processes in expanded skins. PMID- 1863666 TI - Lymphocyte subsets in bone marrow lymphoid nodules and malignant lymphoma nodular involvement. AB - The lymphocyte subsets in 67 cases of bone marrow benign or reactive lymphoid nodules (LN) and 23 cases of nodular involvement by B malignant lymphoma (B-ML) have been immunohistochemically characterized on paraffin embedded trephine biopsies utilizing a panel of 10 monoclonal antibodies. LCA was positive in 90% LN and B-ML lymphocytes; LN2, MB2 stained more than 50% LN and B-ML lymphocytes; MT2 stained more than 50% LN and less than 50% B-ML lymphocytes; UCHL1 stained the 20% of LN lymphocytes; LN1 stained only B cells of the rare germinal centers; MT1 only myeloid cells, L26 only plasma cells. DF-T1 and Leu 22 failed to stain LN or B-ML lymphocytes. While anti-T lymphocyte antibodies reacted inconstantly with lymphoid cells in decalcified and embedded specimens, LCA and some anti-B lymphocyte antibodies gave constantly reproducible results for bone marrow LN and B-ML. They permitted an easy recognition and exact evaluation of the size of LN, the identification of scattered B cells, the detection of the residual or minimal involvement by B-ML and the exact burden of the invasion, but could not allow a convincing differential diagnosis between LN and small cell B-ML nodular involvement. PMID- 1863667 TI - [A dimer of fragment D from stabilized fibrin--a substrate for the destabilase enzyme (gamma-glutamyl-epsilon-lysyl-isopeptidase)]. PMID- 1863668 TI - [Isolation and properties of serine proteinase from Aspergillus oryzae]. AB - A serine proteinase having an activity optimum at pH 6.7-8.2 has been isolated from amylorisine P-10x (a mixture of Aspergillus oryzae enzymes) by chromatography on DEAE-Sephadex A-50 and bacitracin Sepharose 4B. The proteinase is fully inactivated by phenylmethylsulfonylfluoride and diisopropylfluorophosphonate, the specific inhibitors of the enzyme, and has a pI at pH 7.5. The molecular mass of serine proteinase is 30000 Da; its amino acid composition appears as: Met2, Asp33, Thr18, Ser29, Glu21, Pro9, Glu32, Ala38, Val24, Ile16, Leu15, Tyr8, Phe8, His8, Lys18, Arg4, Trp6. The N-terminal sequence of the serine proteinase: Gly-Leu-Thr-Thr-Gln-Lys-Ser-Ala-Pro-Trp-Gly-Leu-Gly-Ser Ile-Ser-Xaa-Lys- Gly-Gln-Gln-Ser-Thr-Asp-Tyr-Ile-Tyr, which coincides practically completely with the corresponding sequence of alkaline proteinase of A. oryzae, ATCC20386, has been determined. Similar to subtilisin, the enzyme catalyzes the condensation of leucine and alanine p-nitroanilides with N-benzyloxycarbonyl alanyl-alanine and glycyl-alanine methyl esters. PMID- 1863669 TI - [Identification of alpha-tropomyosin of the human myocardium by two-dimensional electrophoresis, and sequencing]. AB - Two-dimensional electrophoresis of total cardiac muscle extracts allows the detection of about 200 protein fractions. In preliminary studies the fraction D 10 protein was characterized in terms of relative molecular mass, isoelectric point and quantitative composition as alpha-tropomyosin. The similarity of the protein to human alpha-tropomyosin was confirmed by the results of analysis of the N-terminal sequence of the D-10 protein eluate in a gas-phase sequencer. PMID- 1863670 TI - [Problems of biochemical organization]. AB - Biological organization has been defined as a unity of structure, function and regulation. Biological organization of hierarchical multilevel biological systems is represented by a hierarchy of functioning controllable structures. The hierarchy of levels of material organization predetermines the existence of a hierarchy of regulatory mechanisms. Biochemical organization involves the levels of material organization corresponding to biomacromolecules, supramolecular complexes and cellular organelles. The levels of biomacromolecules and supramolecular structures effectuating elementary functions and controlled by basic regulatory mechanisms occupy key positions in biological systems. These levels play the role of standard functional blocks; their combination leads to hierarchically higher structural levels (cell, tissue, organ, systems of organs, organism) performing more complex functions and controlled by hierarchically more important regulatory mechanisms. The peculiarities of regulation of biological systems that are due to the existence of a hierarchy of regulatory mechanisms are discussed. PMID- 1863671 TI - [Isolation and certain properties of the thermostable endoglucanase from E. coli C600 (pKNE-102) coded by a Clostridium thermocellum gene]. AB - A previously unknown endoglucanase encoded by the C. thermocellum gene was isolated from the recombinant strain of E. coli (pKNE-102). The purification procedure included ammonium sulfate precipitation, heat treatment, chromatography on a polyvinyl matrix (Toyopearl HW-50F) and chromatofocusing on a high performance Mono P HR 5/20 column. Sodium dodecyl sulfate electrophoresis analysis of the Toyopearl HW-50F effluent revealed two protein bands with Mr of 41 kDa and 42 kDa. These protein components differed also by their pI values (4.45, and 4.40, respectively) and could be separated by chromatofocusing. Both components were found to be active and exhibited similar enzymatic properties as well as high thermal stability. PMID- 1863672 TI - [High mobility group proteins: structure, localization, function]. AB - High motility group proteins (HMG) are extracted by 5% HCIO4 and 0.35 M NaCl and are characterized by low molecular mass and a high content of acidic and basic amino acids. There is evidence that HMG are involved in the formation of transcriptionally active chromatin. PMID- 1863673 TI - [Transcortin in rat kidney tissue: distribution in microsomal fractions]. AB - During chromatography of renal tissue cytosolic proteins on DEAE-cellulose the protein specifically binding [3H]corticosterone is eluted within the potassium phosphate concentration range of 0.08-0.10 M. Analysis of kidney slices revealed the synthesis of [3H]transcortin whose electrophoretic mobility was close to that of the blood plasma protein. Using radioimmunochemical methods, it has been found that transcortin-specific [125I]IgG antibodies interact with growing polypeptide chains of membrane-bound polyribosomes. Free polyribosomes do not bind antibodies against transcortin. PMID- 1863674 TI - Diversity of penetration of anti-cancer agents into solid tumours. AB - Failure of anti-cancer agents to reach all clonogenic cells at cytotoxic concentrations is recognized as an important form of resistance in solid tumours. Subcutaneously implanted mammary adenocarcinoma 16/C was used to evaluate the intratumour distribution of five alkylating, bioreductive alkylating and intercalating agents and two radiation sensitizers. The agents were classified according to their in vivo distribution in well- and poorly-perfused tumour regions, as delineated by lissamine green. The classifications were: (1) distribution in direct proportion to the vascular supply; (2) uniform distribution to well- and poorly-perfused tumour regions; and (3) preferential retention in the poorly-perfused tumour regions. Our current state of knowledge did not allow reliable prediction of the classification based on chemical structure or mechanism of action. PMID- 1863675 TI - Growth and cell kinetics of human hair papilla cells in vitro. An autoradiographic and flow cytometric study. AB - Hair papilla, a distinct specialized dermal compartment, plays a fundamental role in the biology of hair growth. Recently some attention has been focused on hair papilla cells (HPC) as possible targets for drugs influencing the hair growth. Isolation and cultivation of the HPC facilitates screening for such drugs. In the present work, growth and cell kinetics of human occipital scalp follicle HPC have been studied in vitro. HPC grow according to a Gompertz function, i.e. with considerable growth delay long before becoming confluent cultures, due probably to elongation of the potential doubling time (Tpot) and to a parallel increasing cell loss rate. The [3H]dT labelling index of the HPC strongly depends on the age of the subculture; the cycle time being about 4 days. A potential doubling time of about 93 h, indicative of growth fraction (GF) = 1, and a duration of S phase and G2 + M phase of about 8 h each were found by the combined application of continuous labelling with [3H]dT and DNA flow cytometry. PMID- 1863676 TI - Streaming kidney. AB - Twenty-five male young adult random bred rats, weighing 250-300 g, were injected with 18.5 kBq/g body weight tritiated thymidine (specific activity 185 GBq/mM). The rats were then killed in groups of five, at the following times: 1 h and 14, 30, 60 and 120 days. The kidneys were processed histologically and dipped into liquid emulsion, exposed for 3 weeks and developed. Kinetic measurements were restricted to juxta-medullary glomeruli, their adjacent convoluted tubules and medullary tubuli. All other nephrons were ignored. The medullary pole of the juxta-medullary glomerulus served as reference point for all measurements and was referred to as the origin. The distance of a labelled cell from the origin was measured with an eye-piece micrometer and expressed in terms of two units: distance (microns) and cell location, defined as the number of cells separating a labelled cell from origin. Since only medullary nephrons were considered, these measurements represent distances directed toward the papilla. One hour after labelling, most cells were in the vicinity of the juxta-medullary glomerulus, not further than 800 microns from the origin in the direction of the papilla. During the following days labelled cells advanced toward the papilla at a daily velocity of 13.8 microns, covering 1.1 locations/day. Kinetically, the juxta-medullary nephron is a two-compartment cell renewal system. Its compartments, the progenitor (P) and the functional (Q), cover locations 0-80 and 81-150, respectively. The first feeds the second with cells. Morphologically, the progenitor compartment includes proximal and distal convoluted epithelia and a part of thick straight tubules. Other nephron portions belong to the Q compartment. It is assumed that the nephrocyte is a part of a cell stream directed toward the papilla, which probably also includes stroma and vasculature. PMID- 1863677 TI - Plasma membrane and intracellular pools of transferrin receptors decline during in vitro cultivation of U937 cells. AB - Transferrin receptor expression in the monocyte-like cell line U937 was investigated during in vitro cultivation. U937 cells expressed a single class of high affinity surface transferrin receptors (KD approximately 4 nM), with apparent subunit Mr of 90-95,000 Da as determined by SDS-reducing PAGE. [125I] transferrin binding studies on detergent-solubilized cells revealed that half to two-thirds of the total functional binding sites were located intracellularly. Radioligand binding, immunofluorescence and flow cytometry studies were performed on intact, detergent-solubilized, or saponin-permeabilized cells, using either transferrin or the anti-transferrin receptor monoclonal antibody OKT9 IgG. These studies demonstrated that functional and antigenic transferrin receptor levels were maximal on cells 24 h after subculture at low density and declined during the culture period. Scatchard analysis of radioligand binding data suggested that the decline in functional transferrin binding sites resulted from a decline in the number of available receptors. These results demonstrate that in U937 cells there is a density-dependent regulation of transferrin receptor expression, resulting in a loss of functional and antigenic receptors from both plasma membrane and intracellular locations. PMID- 1863678 TI - Ameloblast migration in guinea pig molars. PMID- 1863679 TI - [Sensory information processing during general anesthesia-- acoustic-evoked 30-40 Hz oscillations and intraoperative wakefulness during cesarean section]. AB - Neuropsychological and neurophysiological investigations indicate that the underlying framework of adequate sensory information processing is a 30-40 Hz oscillatory brain mechanism, which also can be observed in mid-latency auditory evoked potentials (MLA-EP). Since high incidence of stimuli perception and wakefulness is a phenomenon during Caesarean section under general anaesthesia it was studied if auditory evoked 30-40 Hz oscillation correlate with intraoperative wakefulness during this surgical procedure. Following informed consent, 21 patients were selected for elective Caesarean section. Anaesthesia was induced with thiopentone (5 mg/kg b.w. i.v.) and maintained with thiopentone bolus injection (1-2 mg/kg b.w.i.v). and O2/N2O 1:1 according to clinical signs of adequate anaesthesia. After delivery, a balanced anaesthetic technique using fentanyl, enflurane and N2O in O2 1:1 was employed. Clinical signs of intraoperative wakefulness were spontaneous movements of the limbs, mimics, eye opening, wakefulness after auditory stimulation (tape A: crying baby, tape B: classical music), one hour and 24 hours postoperatively reported dreams, hallucinations and detailed reports about intraoperative events. Auditory evoked potentials were recorded on-line before and during general anaesthesia, during the entire surgical procedure. Latencies of the peaks V, Na, Pa were measured. Employing Fast-Fourier transformation analysis, corresponding power spectra were calculated to analyse energy portions of AEP's frequency components. Spontaneous motoric movements occurred in 60% of the patients and did not correlate with heart rate, blood pressure or other clinical signs of inadequate anaesthesia. Provoked motoric reactions were 4 times as often after presentation of tape A as after tape B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863680 TI - [Successful treatment of a fulminant pulmonary embolism using a high-dose bolus injection of urokinase during cardiopulmonary resuscitation]. AB - Experience has shown that the bolus injection of streptokinase during resuscitation in case of fulminant pulmonary embolism considerably improves the prognosis. In the case presented here a 64-year old female patient with a fulminant pulmonary embolism was injected with 2 x 1,000,000 I.U. urokinase after 20 minutes of unsuccessful cardiopulmonary resuscitation. Ten minutes after the second injection the circulation could be stabilised by drugs only. The patient survived without any lasting damage. The mechanism of fibrinolysis during resuscitation is discussed. It is also possible to check the diagnosis during resuscitation using echocardiography or angiography. However, treatment must usually start immediately only on clinical diagnosis. Resuscitation in the case of a pulmonary embolism can even be successful after much longer than one hour. Contra-indications must be ignored in such cases. Side effects, which are usually haemorrhages, can as a rule be treated. In our opinion urokinase should be given by preference in the bolus injection during resuscitation. The exception to this is the primary operation during resuscitation. Pulmonary embolectomy is also possible after unsuccessful fibrinolysis. PMID- 1863681 TI - [Pathophysiologic and therapeutic aspects of the adult respiratory distress syndrome (ARDS)]. AB - Since the first characterization of the adult respiratory distress syndrome (ARDS), knowledge of its aetiology and pathogenesis has grown considerably. In spite of this, mortality remains up to 50 to 90%, particularly if multiple organ failure is present. Because no causative clinical therapy is available up to now, significant attention is given to preventive measures like early operative stabilisation of long bone fractures, or prophylaxis of nosocomial infections. After clinical manifestation of ARDS, treatment focuses on functional disturbances of the cardiopulmonary system and on the underlying disease. The aim of this symptomatic therapy is to ensure oxygen supply according to the organisms demand. It is still unknown, however, whether the mortality of patients with ARDS can be reduced by optimising the oxygen supply. In general, oxygen supply can be enhanced by improving pulmonary gas exchange, cardiac output and blood oxygen transport capacity. For practical use the therapy often ends up with a therapeutical dilemma: On one hand, the improvement of the pulmonary gas exchange by application of PEEP can be associated with a critical decline in cardiac output, particularly if the afterload of the right ventricle is elevated. On the other hand, to increase cardiac output, both volume replacement and vasodilators can severely affect pulmonary gas exchange if the alveolo-capillary permeability is increased and pulmonary hypoxic vasoconstriction is disturbed. Thus, oxygen supply can be optimised only via invasive monitoring of the cardiorespiratory system. Although still experimental, the most promising approaches seem to be pharmacological interventions directed at suppressing the formation and effects of various humoral and cellular mediators. An improved understanding of the inflammatory processes might provide new insights in the pathophysiology of ARDS and the related therapeutic interventions. PMID- 1863682 TI - [Therapeutic and toxic plasma concentrations and elimination half-lives of commonly used drugs]. AB - For 253 frequently used drugs therapeutic and, if data were available, toxic, and fatal plasma concentrations as well as elimination half-lives were compiled in a table. To assess the significance of drug levels for the therapeutic monitoring of patients, it is essential that a collection of data is readily available. In addition, this list can assist the diagnostic assessment in case of intoxications. PMID- 1863683 TI - [Intravenous methyl iodide poisoning--detoxification using hemoperfusion]. AB - A 19-year-old patient intending to commit suicide gave himself an intravenous injection of about 14 g methyliodide. The patient was admitted to our hospital in a state of somnolence and agitation followed by a cerebral convulsion and severe hypotension. The serum concentration of methyl iodide was measured by mass spectroscopy. In addition to an antidote therapy with acetylcysteine, haemoperfusion was performed followed by a remarkable decrease of the methyliodide concentration. The patient survived this severe intoxication and was discharged from the hospital after a week. PMID- 1863684 TI - [Pulse oximetry monitoring of postanesthetic transportation of ophthalmic surgery patients: risk of hypoxemia despite pre-oxygenation]. AB - 40 adult patients, ASA class I-III, were studied with regard to their arterial oxygen saturation during transportation from the operating room to the recovery room, following ophthalmic surgery under general anaesthesia. Before transportation the patients were breathing oxygen spontaneously for 6 min.; during transportation they were breathing air. The time for the transport from the operating room to the recovery room was between two and eight minutes. Hypoxaemia (SaO2 85-90%) was observed in 18 cases, severe hypoxaemia (SaO2 less than or equal to 85%) in 5 cases. PMID- 1863685 TI - [Esophageal perforation and pneumothorax. Complications due to placement of a stomach tube]. AB - Perforation of the oesophagus, as well as a pneumothorax are described as complications of the use of a nasogastric feeding tube. Clinical tests to determine correct placement are noted to be unreliable and the importance of radiological control, especially in the unconscious patient, ist stressed. The suspected diagnosis of oesophageal perforation should be verified without delay to immediately initiate conservative or surgical treatment. PMID- 1863686 TI - A model for development and evolution of complex morphological structures. AB - How 'complex' or composite morphological structures like the mammalian craniomandibular region arise during development and how they are altered during evolution are two major unresolved questions in biology. Herein, we have described a model for the development and evolution of complex morphological structures. The model assumes that natural selection acts upon an array of phenotypes generated by variation in a variety of underlying genetic and epigenetic controlling factors. Selection refines the integration of the various morphogenetic components during ontogeny in order to produce a functioning structure and to adapt the organisms to differing patterns of environmental heterogeneity. The model was applied to the development and evolution of the mammalian mandible (which is used as a paradigm of complex morphological structures). The embryology of the mandible was examined in detail in order to identify the fundamental developmental units which are necessary to assemble the final morphological structure. The model is quite general since equivalent units exist for the development of many other biological structures. This model could be applied to many other developing morphological structures as well as other groups of organisms. For example, it can be applied to cell parameters during Drosophila development (Atchley, 1987). The model as discussed in this paper assumes that morphological changes in the mandible result from evolutionary changes in its underlying developmental units. The developmental units relate to characteristics of cellular condensations which are produced from the differentiation of embryonic neural crest cells. The developmental units include: the number of stem cells in preskeletal condensations (n), the time of initiation of condensation formation (t), the fraction of cells that is mitotically active within a condensation (f), the rate of division of these cells (r), and their rate of cell death (d). These units and their derivative structures are discussed in terms of types of tissue differentiation (chondrogenesis, osteogenesis, primary/secondary osteogenesis, intramembranous/endochondral ossification) and growth properties of major morphological regions of the mandible. Variation in these five units provides the developmental basis for ontogenetic and phylogenetic modification of mandibular morphology. We have discussed how these developmental units are influenced by (a) the cell lineage from which they arise, (b) epithelial-mesenchymal (inductive tissue) interactions, (c) regulation of cell differentiation, and (d) extrinsic factors such as muscles, teeth and hormones. Evidence was provided that variation in mandibular morphology is heritable, subject to modification by natural selection, and that divergence among different genetic stocks has apparently occurred through changes in these developmental units and their derivative structures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1863687 TI - Time-resolved fluorescence emission and excitation spectroscopy of d(TA) and d(AT) using synchrotron radiation. AB - The photophysics of the sequence isomers d(TA) and d(AT) has been investigated at room temperature in 5 x 10(-5) M neutral aqueous solution using pulsed ultraviolet excitation from the ACO synchrotron and detection by time correlation or gated single-photon counting. Decay profiles of the emissions at 350, 400 and 460 have been analyzed both independently and globally by reiterative non-linear least-squares fitting to models of two and three independently emitting species. No evidence has been observed for excited-state reaction. Time-windowed spectra, both emission and excitation, have been collected for three time windows and have been deconvoluted to give time-resolved spectra using the lifetimes resulting from the decay analyses. Spectra are separated into two classes, with picosecond and nanosecond lifetimes, respectively. The picosecond spectra have the emission and excitation spectral characteristics of mixed monomer (A and T) fluorescences and are assigned as originating from the unstacked fractions of d(TA) and d(AT). The nanosecond emission spectra from d(TA) and d(AT) are both two-component, with lambda max approximately 350 and approximately 425 nm and lifetimes of 2.3 and 6.1 ns, respectively. The time-resolved excitation spectra for the nanosecond emissions are quite different from the isotropic absorption spectra of d(TA) and d(AT) but correlate with the anisotropic absorption for out-of-plane transitions between stacked bases of co-crystals of 9-methyladenine and 1-methylthymine reported by Stewart and Davidson. The nanosecond spectra thus represent the direct excitation and emission of stacked pairs of bases. These results provide no evidence for energy transfer and are probably related to sequence-specific photo-adduct formation. PMID- 1863688 TI - A circular dichroism study of mitochondrial transhydrogenase from beef heart. AB - This paper describes a circular dichroism (CD) spectroscopy study of purified proton-pumping nicotinamide nucleotide transhydrogenase from beef heart. The CD spectrum obtained was used to estimate the content of secondary structures of the purified enzyme and suggests the presence of 40-45% alpha-helical structure and long, possibly membrane-spanning alpha-helices. The spectrum was essentially unaffected by the absence or presence of transhydrogenase substrates, suggesting that the catalytic and proton-translocating activities of the enzyme occur without major rearrangements at the level of secondary structures. PMID- 1863689 TI - Time-resolved synchrotron X-ray diffraction studies of a single frog skeletal muscle fiber. Time courses of intensity changes of the equatorial reflections and intracellular Ca2+ transients. AB - Time-resolved X-ray equatorial diffraction studies on a single frog skeletal muscle fiber were performed with a 10 ms time resolution using synchrotron radiation in order to compare the time courses of the molecular changes of contractile proteins and the intracellular Ca2+ transient during an isometric twitch contraction at 2.7 degrees C. Measurements of the Ca2+ transient using aequorin as an intracellular Ca2+ indicator were conducted separately just before and after the X-ray experiments under very similar experimental conditions. The results, which showed a similar time course of tension to that observed in the X ray experiment, were compared with the aequorin light signal, tension and the intensity changes of the 1,0 and 1,1 equatorial reflections. No appreciable change in both reflection spacings indicated that the effect of internal shortening of the muscle was minimized during contraction. The intensity change of the equatorial reflections generally occurred after the aequorin light signal. In the rising phase, the time course of increase in the 1,1 intensity paralleled that of the rise of the light signal and the intensity peak occurred 20-30 ms after the peak of the light signal. The decrease in the 1,0 intensity showed a time course similar to that of tension and the intensity minimum roughly coincided with the tension peak, coming at 80-90 ms and about 60 ms after the peaks of the light signal and the 1,1 intensity change, respectively. In the relaxation phase, the 1,1 intensity seemed to fall rapidly just before the tension peak and then returned to the original level in parallel with the decay of tension. The 1,0 intensity returned more slowly than the tension relaxation. Thus, the change of the 1,1 intensity was faster than that of the 1,0 intensity in both the rising and relaxation phases. When the measured aequorin light signal was corrected for the kinetic delay of the aequorin reaction with a first-order rate constant of either 50 or 17 s-1, the peak of the corrected light signal preceded that of the measured one by approx. 30 ms. Thus, the peak of the Ca2+ transient appeared earlier than the peaks of the 1,1 and 1,0 intensity changes by 50-60 and 110-120 ms, respectively. The time lag between the extent of structural change and the Ca2+ transient is discussed in relation to the double-headed attachment of a cross-bridge to actin. PMID- 1863690 TI - An estimate of the nearest neighbor base-pair content of 5S RNA using CD and absorption spectroscopy. AB - We analyzed the CD and uv absorption spectra of 5S RNA from Escherichia coli using the method developed in the preceding paper. The analysis of spectra of 5S RNA at 20 degrees C in 0.1M NaClO4, 2.5 mM Na+ (phosphate), pH 7.0, and 0.5 mM MgSO4 gave 7 +/- 3.6 A.U base pairs, 25 +/- 3.6 G.C base pairs, and 7.5 +/- 3.6 G.U base pairs. Estimates of nearest neighbor base pairs were more consistent with the Pieler-Erdmann and the Gewirth-Moore secondary structure models than with the Fox-Woese or the Burns-Luoma-Marshall models. We also examined the structure of 5S RNA as a function of temperature. The melting profile exhibited two transitions--one at about 35 degrees C and one above 50 degrees C. Our spectral data showed that helices I and II were stable during the first transition, and agreed with other data that helix III was the most likely helix to have melted. The results from this in-depth study of 5S RNA indicate that our method of analysis should be useful for studying the secondary structures of other small, unmodified RNAs. PMID- 1863691 TI - A sequence preference for nucleation of alpha-helix--crystal structure of Gly-L Ala-L-Val and Gly-L-Ala-L-Leu: some comments on the geometry of leucine zippers. AB - The synthetic peptide Gly-L-Ala-L-Val (C10H19N3O4.3H2O; GAV) crystallizes in the monoclinic space group P21, with a = 8.052(2), b = 6.032(2), c = 15.779(7) A, beta = 98.520(1) degree, V = 757.8 A3, Dx = 1.312 g cm-3, and Z = 2. The peptide Gly-L-Ala-L-Leu (C11H21N3O4.3H2O; GAL) crystallizes in the orthorhombic space group P212121, with a = 6.024(1), b = 8.171(1), c = 32.791(1) A, V = 1614 A3, Dx = 1.289 g cm-3, and Z = 4. Their crystal structures were solved by direct methods using the program SHELXS-86, and refined to an R index of 0.05 for 1489 reflections for GAV and to an R index of 0.05 for 1563 reflections for GAL. The tripeptides exist as a zwitterion in the crystal and assume a near alpha-helical backbone conformation with the following torsion angles: psi 1 = -150.7 degrees; phi 2, psi 2 = -68.7 degrees, -38.1 degrees; phi 3, psi 32 = -74.8 degrees, -44.9 degrees, 135.9 degrees for GAV; psi 1 = -150.3 degrees; phi 2, psi 2 = -67.7 degrees, -38.9 degrees; phi 3, psi 31, psi 32 = -72.2 degrees, -45.3 degrees, 137.5 degrees for GAL. Both the peptide units in both of the tripeptides show significant deviation from planarity [omega 1 = -171.3(6) degrees and omega 2 = 172.0(6) degrees for GAV; omega 1 = -171.9(5) degrees and omega 2 = -173.2(6) degrees for GAL]. The side-chain conformational angles chi 21 and chi 22 are 61.7(5) degrees and 175.7(5) degrees, respectively, for valine, and the side chain conformations chi 12 and chi 23's are -68.5(5) degrees and (-78.4(6) degrees, 159.10(5) degrees) respectively, for leucine. Each of the tripeptide molecule is held in a near helical conformation by a water molecule that bridges the NH3+ and COO- groups, and acts as the fourth residue needed to complete the turn by forming two hydrogen bonds. Two other water molecules form intermolecular hydrogen bonds in stabilizing the helical structure so that the end result is a column of molecules that looks like an alpha-helix. PMID- 1863692 TI - The structure of [D-Hyi2,L-Hyi4]meso-valinomycin revealed by X-ray analysis. AB - Direct x-ray analysis has been used to determine the crystal structure of [D Hyi2, L-Hyi4]meso-valinomycin (cyclo[-D-Val-D-Hyi-L-Val-L-Hyi-(D-Val-L-Hyi-L-Val D-+ ++Hyi)2-], C60H102N6O18), which crystallized from acetone with two solvent molecules. The crystals are trigonal, space group P32, number of molecules per unit cell Z = 3, cell parameters a = b = 15.2085 (8) A, c = 29.3250 (9) A, gamma = 120 degrees. The standard (R) and weighted (Rw) reliability factors after refinement of the atomic coordinates for C, N, and O atoms in the anisotropic thermal motion approximation, allowing for isotropic H atom contributions, were 0.070 and 0.082, respectively. The molecule adopts a distorted bracelet structure which is stabilized by six N-H ... O = C 4----1 type intramolecular hydrogen bonds. The side chains predominantly occupy external pseudoaxial positions relative to the cylindrical axis of the molecule. In contrast to meso valinomycin, only four of the six Val carbonyl oxygen atoms are directed inwards to form a coordination centre for the molecule, and the carbonyl oxygen atoms of residues D-Val1 and L-Val3 are twisted outward and point away from the centre of the molecule. Although the analogue has a partially formed ion-binding center, it is inaccessible because the hydrophobic isopropyl groups of the D-Hyi2 and L-Hyi4 residues screen the molecular cavity on both sides. PMID- 1863693 TI - Molecular conformation of a D,L stereoisomeric analogue of valinomycin, cyclo[-(L Val-L-Hyi-L-Val-D-Hyi)2-(D-Val-L-Hyi-L-Val-D-Hyi)-]. AB - The crystal structure of a synthetic analogue of valinomycin, cyclo[-(L-Val-L-Hyi L-Val-D-Hyi)2-(D-Val-L-Hyi-L-Val-D -Hyi)-] ([L-Val1, L-Val5]meso-valinomycin), C60H102N6O18, has been determined. Crystals grown from petroleum ether are orthorhombic, space group P2(1)2(1)2(1), with cell parameters a = 16.41(1), b = 18.76(1), c = 25.86(1) A, and Z = 4. The atomic coordinates for nonhydrogen atoms, except those of terminal carbons on one side chain, were refined in the anisotropic thermal motion approximation. The coordinate parameters of the H atoms were incorporated into the structure factor calculations at geometrically expected positions. Values of the standard and weighted R factors after refinement are 0.074 and 0.083, respectively. The crystal structure of the molecule is asymmetric and adopts a conformation with four 4----1 type and one 6- --1 type intramolecular hydrogen bonds between amide nitrogens and carbonyl oxygens. Valinomycin binds potassium more than 100 times strongly than the D,L stereoisomeric analogue, as a result of a different spatial orientation of potentially interacting carbonyl groups. PMID- 1863694 TI - The solution conformation of tubulin-beta(422-434)-NH2 and its Nac-DATADEQG-NH2 fragment based on NMR. AB - The solution conformation of tubulin-beta(422-434)-NH2 (YQQYQDATADEQG-NH2) and its Nac-DATADEQG-NH2 fragment has been studied by two-dimensional 1H-nmr spectroscopy in CD3OH/H2O (90/10 v/v) at neutral and low pH. The 13 amino acid peptide is a segment of the C-terminal region of tubulin, and is directly involved in the selective binding site with microtubule-associated proteins MAP-2 and the tau protein. Based on correlated spectroscopy, total correlation spectroscopy, and rotating frame nuclear Overhauser effect spectroscopy experiments, a complete assignment of all proton resonances was achieved, and the conformation of the backbone could be deduced from coupling constants, NH temperature coefficients, and nuclear Overhauser effects. The spectroscopic evidence indicates that the T8-Q12 section of both molecules forms one complete alpha-helical turn, stabilized by a NH (Q12)-C = O (T8) hydrogen bond. Furthermore, strong pH-dependent backfolding of the E11 side chain to its own NH proton was found. In addition, close proximity between the aromatic side chains of Y1, Y4, and the alpha-helical part, resulting in some substantial chemical shift changes when comparing the entire 13-mer with the octamer, could be explained in terms of a nonclassical kink in the DATA section. The conformational space is dominated by extended structures and the nonextended conformers are only a minor, yet spectroscopically clearly discernible entity. The presence of the alpha-helical region at the C-terminus of the 13-mer is important because binding studies of this peptide with MAP-2 indicate that the D10-E11-Q12-G13 fragment is critical for the binding interaction. PMID- 1863695 TI - Structural determination of the vasoactive intestinal peptide by two-dimensional H-NMR spectroscopy. AB - The structure of the vasoactive intestinal peptide 1-28 in 40% 2,2,2 trifluoroethanol was investigated by two-dimensional 1H-nmr spectroscopy. All 1H resonances, except the gamma, delta, and epsilon protons of the lysine residues, could be sequentially assigned. Numerous intraresidual as well as short-range interresidual nuclear Overhauser effect spectroscopy connectivities were observed. Using a variable-target function minimization, a molecular model consisting of two helical stretches involving residues 7-15 and 19-27 connected by a region of undefined structure was calculated. The existence of an undefined structure between residues 16 and 18 confers mobility to the peptide molecule. PMID- 1863696 TI - Sedative-hypnotic drug use in Canada. AB - Although many studies of sedative-hypnotic drug use have been performed in Canada, there has been no national study of the use of these drugs. We have attempted to correct this deficit in our knowledge by using data from an international survey of health care utilization performed in 1968-9 and from the Canada Health Survey (1978-9), the Health Promotion Survey (1985) and the National Alcohol and Other Drugs Survey (1989) to examine sedative-hypnotic use among individuals aged 15 or more. The results suggest that the use of these drugs in Canada is about average for an industrialized society. Several socioeconomic and health care correlates of sedative-hypnotic use were found. The rate of use of these drugs was higher among women, the elderly, separated, divorced or widowed individuals, those who had a secondary school education or less, individuals with a low family income, the retired, and the unemployed. Among women, higher rates of use were reported by those whose main activity was keeping house (as compared with those who were employed outside the home) and by those who lived alone. Higher rates of use were also found for individuals who had consulted a physician or been hospitalized recently, individuals taking multiple drugs, those who scored highly on an anxiety scale, persons in whom negative feelings predominated, and those who had experienced a high frequency of psycho-physiological symptoms of anxiety and depression. From a regional point of view, the highest rates of use for women were consistently reported from Quebec, while the lowest were consistently found in the Prairie provinces. No consistent pattern was found for men. PMID- 1863697 TI - Historical trends in public general hospitals. AB - This article examines utilization trends in Canadian public general hospitals from 1976 to 1986-87. These trends are then compared with a previous period, and with hospital trends in the United States. Findings for this report are based on both provincial and national data. There was an overall decline in the number of hospitals with a decrease in small (1-49 beds) and an increase in large (300+ beds) hospitals. The net result is a 7% increase in the number of beds, though due to the larger population there was a 3% decrease in the bed rate per population. The bed occupancy rate increased from 77% to 83% and the average length of stay also increased. The number of separations increased slightly but rates per population declined. Patient-days per population increased in most provinces and there was a significant increase in long-stay units. Despite general uniformity amongst the provinces there were some notable variations. The trends indicate a reversal of the situation in the 1953-1973 period which was marked by an expansion in the hospital system. Hospitals in the United States showed somewhat similar trends with the exception of length of stay. The trends may be ascribed to factors such as increased efficiency, the development of alternatives to inpatient care, technical improvements, demographic changes and the individuality of the provincial health care systems. PMID- 1863698 TI - Birth outcomes and infant mortality by income in urban Canada, 1986. AB - For 1986, 219,470 live births were reported for residents of Canada's 25 Census Metropolitan Areas (CMAs). For each of these births, street address information as shown on the birth registration was used to code the census tract where the mother lived. Data by census tract were obtained for 1,650 infant deaths in 1986, and from the 1986 census for the population of 4,727,770 women aged 10-49 in 1986. Births, infant deaths and census population data (adjusted for undercount) were then used to calculate rates of infant mortality, low birth weight (LBW), very low birth weight (VLBW), prematurity, small for gestational age (SGA), and total fertility. The results are presented by neighborhood income quintile group (based on percentage of low income), and by the mother's age, parity (number of live births), marital status and country of birth, as well as by CMA. PMID- 1863699 TI - Births and birth rates, Canada, 1989. PMID- 1863700 TI - Divorces, Canada and the Provinces, 1989. PMID- 1863701 TI - Annual hospital statistics--1987-88. PMID- 1863702 TI - Tuberculosis in Canada, 1989. PMID- 1863703 TI - Proposed factor structure of the Geriatric Depression Scale. AB - The Geriatric Depression Scale (GDS) is commonly used to measure depression in the elderly. However, there have been no reports of the underlying structure of the GDS. To this end, the GDS was administered to 326 community-dwelling elderly subjects, and the data were subjected to a factor analysis. A five-factor solution was selected and, after a varimax rotation, the factors that emerged could be described as: (1) sad mood, (2) lack of energy, (3) positive mood, (4) agitation, and (5) social withdrawal. This solution accounted for 42.9% of the variance. Knowledge of the factor structure should aid both clinicians and researchers in the interpretation of responses on the GDS. PMID- 1863704 TI - Dementia and cognitive impairment in the oldest old: a comparison of two rating methods. AB - Rates of cognitive impairment in a representative population of the oldest old (aged 84 to 90) were examined using two indicators: The Global Deterioration Scale (GDS), and a Cognitive Rating (CR) derived from performance on five neuropsychological tests. Prevalence was estimated at 25.3%, using the GDS, and 30% with the CR. The overall degree of congruence between the measures was high, with most disagreements involving mildly impaired cases. The results indicate a high degree of convergence of clinical and neuropsychological indicators. The findings also confirm high rates of impairment among the oldest old. PMID- 1863705 TI - Borderline personality disorder in late life. AB - Records of eight elderly patients identified as BPD by a geriatric team were analyzed for compliance with DIB-R and DSM-III-R criteria. A nonborderline control group was randomly selected and matched for age, gender and residence. Clinicians experienced in geriatric mental health performed retrospective chart reviews and found that not one clinically diagnosed BPD patient was identified by either instrument. Although there appear to be a number of constant features of BPD throughout life, this study delineated two major areas of change in BPD in late life. PMID- 1863706 TI - Seasonal distribution of births in Alzheimer's disease. AB - We obtained season-of-birth data in 727 autopsy-confirmed cases of Alzheimer's Disease (AD) and compared these data with expected general population birth rates. There were no significant differences between quarterly birth rates in the AD group and expected quarterly birth rates. Edward's test for cyclical trends did not establish a peak period of birth in the AD sample. No significant differences between observed and expected quarterly birth rates were found when data were analyzed with regard to either family history of dementia or to gender. Edward's test for peak quarter was significant for AD females, however, with the peak period occurring early in the first quarter. These negative findings between observed and expected quarterly birth rates, based on the large number of autopsy confirmed AD cases in this study, suggest that a season-of-birth effect in AD is highly unlikely. PMID- 1863707 TI - Suicide in later life: psychological autopsy findings. AB - The authors report preliminary data from a psychological autopsy study of completed suicide in late life. Sixteen of 18 victims had diagnosable psychopathology, most commonly major depression of late onset. Symptoms manifest prior to death are described and directions for future investigation discussed. The psychological autopsy is shown to be a viable method for studying suicide in the elderly. PMID- 1863708 TI - Effects of hospitalization on affective status of elderly patients. AB - The effects of hospitalization on affective status were assessed by an original protocol in 214 consecutive elderly patients (mean age = 78.3 +/-5.0 years, range = 70-92 years). Psychological decompensation was significantly related to length of stay (p less than 0.01) and drug use (p less than 0.05) and unaffected by sex, marital status, prior living place, diagnostic category. Affective status and functional status were directly correlated (p less than 0.0001), although in 51% of medical patients the affective status worsened or remained unchanged despite improved physical function. Improvement in affective status occurred more frequently in surgical patients (p less than 0.001) due to psychological improvement following surgery. Physicians providing medical and surgical care for geriatric patients must remain aware of the patients' emotional response to hospitalization and illness, given the accompanying risk for psychological decompensation. PMID- 1863709 TI - Psychogeriatrics and medical informatics. PMID- 1863710 TI - Research activity at the Max Planck Institute for Psychiatry (Munich): depression in later life. PMID- 1863711 TI - Characterization of the LDL receptor in rat promegakaryoblasts in culture. AB - Rat promegakaryoblasts (RPM, a precursor platelet cell line) in culture exhibited a capacity to bind, take up and degrade 125I-LDL. The low density lipoprotein (LDL) binding showed the following characteristics: (a) high affinity, (b) saturability, (c) specificity, (d) down-regulation, after exposure to 25 hydroxycholesterol. Furthermore the proteolytic degradation of 125I-LDL by RPMs was inhibited by chloroquine which interferes with the lysosomal degradation processes. These findings show LDL receptor cell biology of RPM to be of the classical type and to differ from that of platelets. PMID- 1863712 TI - Evidence for the regulation of the activity of protein kinase C through changes in membrane properties. AB - We measured the effects of two branched-chain analogs of distearoyl phosphatidylcholine, containing either a methyl or an n-butyl group at the 8 position, on the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine. The former compound raised the bilayer to hexagonal phase transition temperature while the latter compound lowered it. The opposite effects of these amphiphiles on protein kinase C activity (inhibition and activation, respectively) correlated with their effects on lipid polymorphism. Because of the similarity of the structures of these two compounds, it seems likely that their opposite effects on the activity of protein kinase C is a result of their alteration of the lipid environment of the membrane rather than to binding to a specific site on the protein. We also compared the effects of hexachlorophene on lipid polymorphism and protein kinase C activity at high and at low calcium concentrations. We also found that the effect of hexachlorophene forming a complex with Ca2+ is to increase both the hexagonal phase forming propensity of the membrane as well as to increase the activity of protein kinase C, again demonstrating the correlation between lipid phase propensity and effects on protein kinase C activity. PMID- 1863713 TI - Effect of three organophosphates on respiration in rat brain and liver tissue. AB - The effects of three organophosphate pesticides, i.e. monocrotophos, dichlorvos, and phosphamidon on respiration in rat brain and liver tissue slices have been studied. Among these pesticides dichlorvos causes significant inhibition of respiration both in brain and liver. PMID- 1863714 TI - Mitochondrial activity and development: energy carrier selection in a controlled reaction mechanism. AB - There is evidence of an important role carried out by mitochondria and by proteins of mitochondrial origin during key moments of development. We assume that it is possible to represent the energy activity of the cell through the level of ATP production and we propose a simple model system for the ATP/ADP cycle. The model takes into account the basic aspect of ATP dynamics in macromolecular synthesis and involves the possibility of selection between states of high and low protein production. A simple extension of the model leads to the creation of a mechanism enabling the establishment of self-sustained oscillations. PMID- 1863715 TI - On the skew distribution of immunoglobulins and the inverted protein-folding problem. AB - The question of antibody specificity is discussed in the framework of the inverted protein-folding problem (i.e. the characterization of protein sequences with a common fold). A stochastic model of the immune response, patterned after a model for the distribution of words in natural languages is proposed. It is shown that the steady-state probability distribution of immunoglobulin variable-region frequencies is the Yule distribution. PMID- 1863716 TI - A continuum model of contraction waves and protoplasm streaming in strands of Physarum plasmodium. AB - We present a mathematical model for continuously distributed mechanochemical autooscillations (autowaves) in a protoplasmic strand of Physarum polycephalum. The model is based on a hypothesis of local positive feedback between deformation and contraction of the contractile apparatus. This feedback is mediated through a cell regulatory system whose kinetics involves coupling to mechanical strain. Mathematical analysis and computer simulations have demonstrated that the solutions of the model agree quantitatively with the available experimental data. In particular, hydrodynamic interaction alone, between different sections of the strand via the streaming endoplasm, is capable of inducing the characteristic contractile behavior. PMID- 1863717 TI - A system control framework for the self-fertilization and selection process of breeding. AB - The self-fertilization and selection process is the main method for speeding up the purifying course of a hybrid population in breeding. This is a complex combinatorial random process with large time delay. To raise the control effectiveness and efficiency of the process, we try, in this paper, to construct a mathematical model of the process by means of effective factors. Then, a control framework for the process is presented which can be used as a guide by breeders for helping them in selecting appropriate control actions. PMID- 1863718 TI - On the divergence of species. AB - Speciation may be considered as a kind of non-equilibrium phase transition which is caused by bifurcation at a critical point of instability. It can be shown that multiple branching of an evolutionary tree is highly improbable, since non degenerate mathematical models describe only binary branchings. PMID- 1863719 TI - Oxygen toxicity and microbial evolution. AB - It is postulated that the role of oxygen toxicity in the evolution of life strongly depends on the origin of molecular oxygen, due to the strong redox buffering capacity of Precambrian waters containing large amounts of ferrous and manganese cations. The critical selective pressure could be observed only after aerobic photosynthesis had been developed, due to the high local concentration of oxygen in close vicinity of photosynthesizing cells. It is also postulated that early oxygen-evolving organisms excreted a substantial part of this element in the form of hydrogen peroxide. As a consequence of the high reactivity of this compound with ferrous and manganese cations, an important percentage of iron deposits were produced with H2O2 as a major oxidant after the development of aerobic photosynthesis. It is postulated that negatively charged extracellular polymers of simple pro- and eukaryotic organisms function as sacrificial targets of hydroxyl radicals and at the same time as extracellular equivalents of superoxide dismutases, in these two ways protecting cellular membranes against oxidative damage. The role of oxygen toxicity in developing aerobic mechanisms of iron uptake is also discussed. PMID- 1863720 TI - Search for eukaryotic motility proteins in spirochetes: immunological detection of a tektin-like protein in Spirochaeta halophila. AB - The serial endosymbiotic theory (SET) for the spirochete origin of undulipodia (cilia and eukaryotic flagella) predicts that a greater number of axonemal proteins will show homology to spirochete than to other bacterial proteins. To continue testing, the SET proteins associated with eukaryotic motility (tektin, centrin and calmodulin) were sought in Spirochaeta halophila. Western blot immunological detection techniques (for tektin and centrin) and two-dimensional gel analysis (for calmodulin) were used. Tektins are filamentous proteins extending the length of the axoneme in sperm tails and other undulipodia. Whole cell extracts of S. halophila were probed with antibodies made against three sea urchin (Lytechinus pictus) sperm axonemal tektins (tektins A, B, and C). In the spirochetes, one tektin-like protein was detected as a band on Western blots (a C tektin.) An antibody made against Lytechinus pictus sperm tail axonemes, affinity purified against the C tektin of another sea urchin, Stronglyocentrotus purpuratus, bound to a 30 kDa protein from Spirochaeta halophila. The C tektin epitope was not detected in Escherichia coli. Both the poly- and monoclonal anti centrin antibodies cross-reacted with multiple proteins in the control alga (Tetraselmis striata) and in the putatively negative control bacterium E. coli. No cross reaction was seen between any anti-centrin antibody and S. halophila. Neither did a two-dimensional gel analysis reveal the presence of calmodulin in these spirochetes or in the two other prokaryotes tested (Spiroplasma citri, Acholeplasma laidlawii). Although neither centrin nor calmodulin were detected, a 30 kDa tektin-like protein apparently is present in these spirochetes. PMID- 1863721 TI - Opioid (alfentanil) anesthesia: dose is important, but when it is given and what plasma concentration results may be more important. PMID- 1863722 TI - High-dose alfentanil for myocardial revascularization: a hemodynamic and pharmacokinetic study. AB - It has been suggested that high plasma levels of alfentanil are required in order to control hemodynamic responses to noxious stimuli in patients undergoing myocardial revascularization. The present study was designed to determine the hemodynamic profile in 10 patients and the time course of alfentanil plasma concentrations and pharmacokinetics (7 patients) during and following coronary artery surgery using alfentanil administration based on an overdosage principle. Premedication consisted of lorazepam, 0.07 mg/kg, given 2 hours before surgery. Ten milligrams of alfentanil was given over 5 minutes for anesthesia induction, followed by an infusion of 60 mg/h until sternotomy and 30 mg/h up to skin closure. Additional 5-mg boluses were given prior to noxious intraoperative events. Hemodynamic measurements were performed prior to cardiopulmonary bypass. Blood was sampled simultaneously prebypass and then during the postbypass period for determination of alfentanil plasma levels. The very high alfentanil plasma concentrations achieved provided satisfactory intraoperative conditions in most, but not all, patients. Recovery time was short, despite the large amounts of narcotic used. It is concluded that very high doses of alfentanil associated with lorazepam premedication resulted in hemodynamic stability and markedly elevated narcotic plasma concentrations in most patients. Such plasma levels seem to provide satisfactory anesthetic conditions. PMID- 1863723 TI - Blood/gas solubility coefficient and blood concentration of enflurane during normothermic and hypothermic cardiopulmonary bypass. AB - The blood/gas solubility coefficient and blood concentration of enflurane were measured at intervals in 10 patients undergoing coronary artery revascularization with cardiopulmonary bypass (CPB) and moderate hypothermia. A constant end-tidal concentration of enflurane was maintained throughout the study. Blood/gas solubility coefficient was determined at 37 degrees C, which when combined with an initial single-step equilibration of the blood sample with air, permitted the accurate measurement of blood concentration. Blood/gas solubility coefficient and blood concentration both decreased significantly with the onset of CPB. During the period of hypothermia, blood/gas solubility as measured at 37 degrees C showed little change; however, there was a progressive, marked increase in blood concentration with a mean increase of 80% prior to rewarming. Therefore, the level of anesthesia provided by enflurane may lighten with the onset of CPB, and a deeper level will accompany any decrease in blood temperature. On rewarming, blood concentration levels rapidly returned to levels similar to those measured before cooling. The increased uptake and accumulation of volatile anesthetic agent that occurred as a result of the period of hypothermic CPB was rapidly cleared. The rapidity with which blood concentration responded to the changes occurring during CPB make it unlikely that there was any significant increase in myocardial depression in response to the raised blood concentration secondary to the hypothermia. PMID- 1863724 TI - Hemodynamic performance and histamine levels after desmopressin acetate administration following cardiopulmonary bypass in adult patients. AB - Sixteen patients undergoing cardiac surgical procedures were prospectively randomized into two groups to study the hemodynamic and histamine-releasing effects of desmopressin acetate (DDAVP) administration after cardiopulmonary bypass. Ten minutes after administration of protamine for reversal of heparin, DDAVP, 0.3 microgram/kg, was infused intravenously over 5 seconds in group 1, and the same dose of DDAVP was administered over 5 minutes as an infusion in group 2. There were no statistical differences between baseline values in groups 1 and 2. DDAVP decreased mean arterial pressure by 30% and 25% in groups 1 and 2 (69 +/- 5 mm Hg to 52 +/- 8 mm Hg, P less than 0.005, and 79 +/- 20 mm Hg to 55 +/- 8 mm Hg, P less than 0.005), respectively. The hypotension in both groups was related to decreases in systemic vascular resistance (1,616 +/- 262 dyne.s.cm-5 to 1,073 +/- 199 dyne.s.cm-5, P less than 0.005, and 1,850 +/- 541 dyne.s.cm-5 to 1,144 +/ 214 dyne.s.cm-5, P less than 0.005). Phenylephrine infusion successfully treated the DDAVP-induced hypotension in all patients. Arterial histamine levels at 3 and 5 minutes after infusion of DDAVP did not differ significantly from baseline values. It is concluded that DDAVP at 0.3 microgram/kg is a potent vasodilator when administered intravenously and that histamine is not involved in producing its hypotensive effects. PMID- 1863725 TI - Desmopressin acetate is a mild vasodilator that does not reduce blood loss in uncomplicated cardiac surgical procedures. AB - Desmopressin acetate (DA) is a synthetic analog of vasopressin that may improve perioperative coagulation in cardiac surgical patients. Twenty-seven adult patients with good left ventricular function and normal preoperative coagulation profiles scheduled to undergo elective cardiac surgery participated in the double blinded, placebo-controlled study. The 14 patients in the DA group received the drug over 10 minutes (starting 15 minutes after protamine administration). The 13 patients in the placebo group received an equal volume of saline. Preoperative template bleeding time was longer in the placebo group (P = 0.04). Otherwise, there were no statistically significant differences between the groups in demographics, coagulation variables, renal concentrating function, blood loss, or transfusion requirements at any study interval. The only significant hemodynamic differences detected were an increase in cardiac output in the DA group and a corresponding decrease in systemic vascular resistance. Five of 13 patients who received DA required treatment for hypotension, whereas none of 12 patients who received placebo required treatment during the infusion (P = 0.008). The authors conclude that DA causes mild vasodilation, but does not reduce blood loss or transfusion requirements in patients undergoing primary uncomplicated cardiac surgical procedures. PMID- 1863726 TI - Hemodynamic responses to desmopressin acetate after CABG: a double-blind trial. AB - Despite controversial results concerning its effectiveness, cardiac surgical patients commonly receive desmopressin acetate (DDAVP) after cardiopulmonary bypass (CPB) in an effort to prevent or control bleeding diathesis. The side effects associated with DDAVP are usually considered benign. However, numerous authors have observed episodes of severe hypotension after DDAVP. As a part of a larger trial of DDAVP in routine first-time coronary artery bypass grafting (CABG), this randomized double-blind study of the hemodynamic effects of DDAVP was performed. Fifteen patients received DDAVP (0.3 microgram/kg over 15 minutes) and another 15 received saline placebo after skin closure. A statistically significant decrease in mean arterial pressure (MAP) was observed at 5 minutes after the beginning of DDAVP administration and the maximum decrease (mean change, -21 +/- 8 mm Hg, P less than 0.001) was reached as the infusion was completed. MAP did not change significantly in the control group. Hypotension after DDAVP was associated with a corresponding decrease in systemic vascular resistance. Postoperative blood loss was not different between the groups. It is concluded that routine administration of DDAVP to CABG patients is inadvisable because hemodynamic side effects are potentially dangerous and therapeutic benefit is highly unlikely. PMID- 1863727 TI - Alprazolam withdrawal presenting as delirium after cardiac surgery. PMID- 1863728 TI - Pharmacokinetics of dantrolene in an adult patient undergoing cardiopulmonary bypass. PMID- 1863729 TI - Anesthetic management of a hypothyroid cardiac surgical patient. PMID- 1863730 TI - Perioperative management of coronary artery bypass surgery in a patient with factor IX deficiency. PMID- 1863731 TI - Case 2--1991. A 50-year-old man undergoing a right thoracotomy experiences unexpected intraoperative hypotension due to a drug interaction. PMID- 1863732 TI - The choice of inotropes following cardiopulmonary bypass. Pro: amrinone is a first-choice inotrope following cardiopulmonary bypass. PMID- 1863733 TI - The choice of inotropes following cardiopulmonary bypass. Con: amrinone is not a first-choice inotrope following cardiopulmonary bypass. PMID- 1863734 TI - Accurate identification of the pediatric internal jugular vein. PMID- 1863735 TI - An easy way to safely tie a double-lumen tube. PMID- 1863736 TI - A simple underwater seal apparatus for use in emergencies. PMID- 1863737 TI - Magnesium: its time has come. PMID- 1863738 TI - Hypomagnesemia is common following cardiac surgery. AB - Hypomagnesemia is a common disorder in noncardiac surgical patients in the postoperative period, but the effect of cardiac surgery on serum magnesium concentrations remains unclear. The authors hypothesized that cardiac surgery is associated with hypomagnesemia, and prospectively studied 101 subjects (60 +/- 13.1 years of age) undergoing coronary artery revascularization (n = 70), valve replacement (n = 24), or both simultaneously (n = 7). Blood samples and clinical biochemical data were collected before induction of anesthesia, prior to cardiopulmonary bypass (CPB), immediately after CPB, and on postoperative day 1. Blood samples were analyzed for ultrafilterable magnesium, total magnesium, ionized calcium, parathyroid hormone, and free fatty acid concentrations. Outcome variables were also determined. Eighteen of 99 (18.2%) subjects had hypomagnesemia preinduction and this number increased to 71 of 100 (71.0%) following cessation of CPB (P less than 0.05). Patients with postoperative hypomagnesemia had a higher frequency of atrial dysrhythmias (22 of 71 [31.0%] v 3 of 29 [10.3%], P less than 0.05) and required prolonged mechanical ventilatory support (22 of 63 [34.9%] v 4 of 33 [12.1%], P less than 0.05). Hypomagnesemia is common following cardiac surgical procedures with CPB and is associated with clinically important postoperative morbidity. PMID- 1863739 TI - An improved lidocaine infusion protocol for cardiac surgical patients. AB - A new protocol for lidocaine administration was tested to determine whether it would provide higher free and total serum lidocaine concentrations during and after weaning from cardiopulmonary bypass (CPB), without leading to accumulation toxicity, than those resulting from a conventional protocol (1.5 mg/kg loading dose bolus + 2 mg/min infusion rate). Ten elective adult cardiac surgical patients were studied. Ten seconds prior to aortic cross-clamp release (0 min), each patient received a lidocaine bolus (1.5 mg/kg) and simultaneous lidocaine infusion (5 mg/min for 1 hour, followed by 2 mg/min for 23 hours). Weaning occurred 20 to 30 minutes after cross-clamp release. Lidocaine levels were determined from arterial blood samples at 0, 10, 20, 30, and 60 minutes, and at 2, 4, and 24 hours postcross-clamp release. Compared with the conventional protocol, the new protocol showed a significant increase in mean total lidocaine concentration (P less than or equal to 0.02) at 30 and 60 minutes, and a significant increase in mean free lidocaine concentration (P less than or equal to 0.005) at 20, 30, and 60 minutes. No patient had toxic levels at 24 hours. Results of this study suggest that in patients undergoing cardiac surgery, a "5 + 2" mg/min infusion protocol is safe and superior to a conventional protocol in achieving therapeutic serum levels of free and total lidocaine. PMID- 1863740 TI - The effects of global normothermic hypoperfusion on the processed electroencephalogram in patients. AB - This study examined the effects of global normothermic hypoperfusion on the compressed spectral array (CSA) processed electroencephalogram (EEG) during high dose narcotic anesthesia. Fifteen patients undergoing cardiac electrophysiologic surgery were studied. The patients were anesthetized with a standard high-dose narcotic technique and then connected to a Nicolet Pathfinder I CSA EEG analysis system using seven subdermal electrodes in a modified International 10-20 configuration. There were 167 intervals of profound hypotension ranging from 8 to 96 seconds. During these periods the cerebral perfusion pressure was almost zero. Despite 38 intervals up to 32 seconds long, 6 of the 15 patients had no EEG changes. Overall, there were 36 (21.6%) ischemic EEG recordings. None of the patients developed neurological complications. The incidence of EEG changes was much lower than expected from other studies. Either the processed EEG was inherently insensitive, the high-dose narcotic masked the processed EEG effects of hypoperfusion, or the narcotic provided a previously unknown protective effect. PMID- 1863741 TI - Heparin rebound: a comparative study of protamine chloride and protamine sulfate in patients undergoing coronary artery bypass surgery. AB - Heparin rebound has been suggested to occur when protamine sulfate, but not protamine chloride, is used to neutralize heparin. This study was undertaken to compare these two protamine salts in 32 patients undergoing coronary artery bypass surgery. Initial heparin and subsequent protamine doses were determined by constructing a heparin-activated coagulation time response curve. Heparin was neutralized either with protamine sulfate or protamine chloride. The total protamine/heparin dose ratio was 0.71 +/- 0.05 for protamine sulfate and 0.77 +/- 0.07 (mg/100 U) for protamine chloride. The initial neutralization effect, the subsequent behavior of the plasma heparin level, and the various coagulation parameters did not differ significantly between the groups. Two hours after neutralization, a small and temporary increase of plasma heparin level was observed in both groups. The postoperative blood losses were comparable in both groups. Thus, protamine chloride was not a clinically superior antidote to heparin than protamine sulfate. The observed heparin rebound levels were low and clinically insignificant in terms of blood loss, but they were associated with slight changes in coagulation monitoring. PMID- 1863742 TI - The role of plasma proteins in formation of obstructive protamine complexes. AB - Formation of complexes between heparin and protamine (in saline), or heparin, plasma proteins, and protamine (in plasma) was assessed by measurements of light transmission through different test solutions. To examine the formation of these complexes, 125I-labeled protamine was used. Addition of 125I-protamine to plasma or blood resulted in the sedimentation of 125I-protamine in the form of insoluble complexes. This complex formation was not affected by the presence of heparin, suggesting that protamine-plasma protein interaction may be primarily responsible for precipitation of 125I-protamine. To assess the capability of these complexes to obstruct the pulmonary circulation, an in vitro experimental model was developed. Citrated serum, plasma, blood, or saline were allowed to flow through a glass bead column with the help of a peristaltic pump. A pressure transducer positioned before the column allowed pressure measurements at a constant flow rate during the experiment. Mixing of protamine with plasma or blood prior to their passage through the glass bead column resulted in a significant increase in pressure suggesting that the column was being clogged with insoluble complexes. The increase in pressure occurred both in the presence and absence of heparin in plasma or blood. Under identical experimental conditions, the increase in pressure was insignificant when protamine was added to saline or serum regardless of whether heparin was present or absent. This was further confirmed by the use of 125I-protamine. These observations suggest that protamine forms insoluble complexes with certain plasma proteins. Based on these observations, it is hypothesized that following intravenous administration, protamine immediately forms complexes in circulating blood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863743 TI - Increased pulmonary artery perforating potential of pulmonary artery catheters during hypothermia. AB - The rate of major complications from the use of pulmonary artery (PA) catheters has been reported to be as high as 9%, 0.2% of which may be attributed to PA perforation, a catastrophe with a fatal outcome more than 50% of the time. Although an uncommon event generally, more than one third of catheter-related PA perforations occur during cardiac surgery. Several factors act to advance the balloon-tipped PA catheter into the distal PA, where, during hypothermia, the catheter hardens and, thus, may be more likely to perforate the vessel. The relative contribution of hypothermia, itself, to the perforating potential of previously used, triple-lumen PA catheters (n = 5) was examined in vitro by mounting them in a temperature-controlled testing chamber, at a 90 degrees incident angle to a polyethylene membrane, which represented the PA wall. The membrane was made to pulsate 80 times/min against the PA catheter until it was perforated. Each catheter was tested 5 times each at 3 temperatures. At 35 degrees C, 30 degrees C, and 25 degrees C, the number of pulsations to produce perforation (perforation rate) was 488 +/- 280, 309 +/- 242, and 97 +/- 234, respectively. The perforation rates differed significantly between temperatures (P less than 0.01), but not between catheters or tests at the same temperature. This study demonstrates that perforation of a model PA by a triple-lumen PA catheter is 500% more likely during hypothermia. PMID- 1863744 TI - Effects of isoflurane and fentanyl on ischemic myocardium in dogs: assessment by end-systolic measurements. AB - The effect of anesthetics on ischemic myocardium to which blood was supplied by a stenotic coronary artery was investigated in dogs. The ischemia was assessed by regional wall motion (ultrasonic dimension technique) using fractional shortening (FS) [(EDL - ESL)/EDL x 100] and end-systolic pressure-segment length relationships (ESPLR). The latter is considered to be a more load-independent measure of regional myocardial function. Isoflurane and fentanyl were chosen as anesthetics of current interest. On reducing the left circumflex coronary artery (LCX) flow to approximately 50% of its resting value, a decrease in FS and a rightward shift in ESPLR were observed in myocardium perfused by the LCX. Simultaneously, increases in FS were observed in the nonischemic area perfused by the left anterior descending coronary artery (LAD), which was most likely due to the intraventricular unloading effect. No significant changes of ESPLR were observed in the area supplied by LAD. Isoflurane induced a dose-dependent decrease in FS and a rightward shift in ESPLR in the ischemic myocardial segment, whereas fentanyl caused an increase in FS and tended to shift ESPLR leftward in the same area. The results suggest that isoflurane may have deleterious effects on preexisting myocardial ischemia, whereas fentanyl may not when loading conditions are taken into consideration. Fractional shortening and ESPLR seem to provide similar information about regional myocardial function. PMID- 1863745 TI - The use of amrinone and norepinephrine for inotropic support during emergence from cardiopulmonary bypass. PMID- 1863746 TI - Reversal of refractory right ventricular failure with amrinone. PMID- 1863747 TI - The relevance of somatosensory evoked potentials during thoracic aorta aneurysm repair. PMID- 1863748 TI - Anesthetic and postoperative management of single-lung transplantation. PMID- 1863749 TI - Case 3--1991. A 69-year-old man undergoing a thoracoabdominal aneurysm resection receives intraoperative plasmapheresis to decrease autologous and banked blood requirements. PMID- 1863750 TI - Pro: desmopressin is of value in the treatment of post-cardiopulmonary bypass bleeding. PMID- 1863751 TI - Con: desmopressin is not of value in the treatment of post-cardiopulmonary bypass bleeding. AB - Following two early promising reports that treatment with intravenous DDAVP was helpful in reducing postoperative hemorrhage and the amount of transfusion with homologous blood products in patients who had undergone cardiac surgery with CPB, these results were not repeated in any of the follow-up studies. At the present time, the routine prophylactic use of DDAVP in cardiac surgery cannot be recommended for patients undergoing closure of atrial septal defect, valve repair or replacement, primary CABG, or in children requiring cardiac surgery. The use of DDAVP in complicated procedures or for control of severe postoperative bleeding remains controversial. In the authors' opinion, DDAVP should not be used in cardiac surgery except in patients with a presurgical DDAVP-responsive coagulopathy. PMID- 1863752 TI - Lung isolation during thoracic aneurysmectomy. PMID- 1863753 TI - Rigid bronchoscopy revisited. PMID- 1863754 TI - Univentricular fibrillation. PMID- 1863755 TI - Obstruction of an emergency femorofemoral cardiopulmonary bypass circuit by a pulmonary artery catheter. PMID- 1863756 TI - The incidence of ventricular dysrhythmias during pulmonary artery catheter removal. PMID- 1863757 TI - Pea chloroplast DNA primase: characterization and role in initiation of replication. AB - A DNA primase activity was isolated from pea chloroplasts and examined for its role in replication. The DNA primase activity was separated from the majority of the chloroplast RNA polymerase activity by linear salt gradient elution from a DEAE-cellulose column, and the two enzyme activities were separately purified through heparin-Sepharose columns. The primase activity was not inhibited by tagetitoxin, a specific inhibitor of chloroplast RNA polymerase, or by polyclonal antibodies prepared against purified pea chloroplast RNA polymerase, while the RNA polymerase activity was inhibited completely by either tagetitoxin or the polyclonal antibodies. The DNA primase activity was capable of priming DNA replication on single-stranded templates including poly(dT), poly(dC), M13mp19, and M13mp19 + 2.1, which contains the AT-rich pea chloroplast origin of replication. The RNA polymerase fraction was incapable of supporting incorporation of 3H-TTP in in vitro replication reactions using any of these single-stranded DNA templates. Glycerol gradient analysis indicated that the pea chloroplast DNA primase (115-120 kDa) separated from the pea chloroplast DNA polymerase (90 kDa), but is much smaller than chloroplast RNA polymerase. Because of these differences in size, template specificity, sensitivity to inhibitors, and elution characteristics, it is clear that the pea chloroplast DNA primase is an distinct enzyme form RNA polymerase. In vitro replication activity using the DNA primase fraction required all four rNTPs for optimum activity. The chloroplast DNA primase was capable of priming DNA replication activity on any single-stranded M13 template, but shows a strong preference for M13mp19 + 2.1. Primers synthesized using M13mp19 + 2.1 are resistant to DNase I, and range in size from 4 to about 60 nucleotides. PMID- 1863758 TI - Analysis of unstable RNA transcripts of insecticidal crystal protein genes of Bacillus thuringiensis in transgenic plants and electroporated protoplasts. AB - We have examined expression of several insecticidal crystal protein (ICP) genes of Bacillus thuringiensis in transgenic tobacco plants and electroporated carrot protoplasts. We determined that low levels of lepidopteran toxin cryIA(b) ICP gene expression in plants and electroporated carrot cells is due to RNA instability. We used a series of 3' deleted by cryIA(b) constructs directed by the cauliflower mosaic virus 35S promoter to demonstrate that this instability is minimally contained in the first 579 bases of the gene in both systems. This instability may result from 5'----3' as well as 3'----5' RNA metabolism. The coleopteran toxic cryIIIA gene was also examined in electroporated carrot cells, and found to be poorly expressed. A model for improvement of ICP RNA stability in plants is presented. PMID- 1863759 TI - Environmental conditions differentially affect vir gene induction in different Agrobacterium strains. Role of the VirA sensor protein. AB - The induction of vir gene expression in different types of Agrobacterium strains shows different pH sensitivity profiles. The pH sensitivity pattern demonstrated by octopine Ti strains was similar to that of a supervirulent leucinopine Ti strain, whereas this was different from that shown by nopaline Ti strains and agropine Ri strains. Data are given which indicate that these differences are due to different properties of the virA genes of these wild types. An exceptional case was formed by strains with the limited-host-range plasmid pTiAG57 which showed AS-dependent vir induction only if reduced inoculum sizes were used and the temperature was 28 degrees C or below. PMID- 1863760 TI - Molecular cloning and nucleotide sequencing of the rubber elongation factor gene from Hevea brasiliensis. PMID- 1863761 TI - Nucleotide sequence of cDNA for an endopeptidase (EP-C1) from pods of maturing Phaseolus vulgaris fruits. PMID- 1863762 TI - Nucleotide sequence of a cDNA clone encoding the precursor of the 33 kDa protein of the oxygen-evolving complex from wheat. PMID- 1863763 TI - Nucleotide sequence of a 25S rRNA gene from mustard (Sinapis alba). PMID- 1863764 TI - The complete nucleotide sequence of the intergenic spacer region of an rDNA operon from Brassica oleracea and its comparison with other crucifers. PMID- 1863765 TI - Nucleotide sequence of a wheat (Triticum aestivum L.) cDNA clone encoding the waxy protein. PMID- 1863766 TI - Structure of a chalcone synthase gene from Hordeum vulgare. PMID- 1863767 TI - Identification of novel genes specifically expressed in Chlamydomonas reinhardtii zygotes. AB - The maturation of zygotes formed by the fusion of two gametes is the essential part of the diploid phase of the Chlamydomonas reinhardtii sexual life cycle and results in mature zygotes competent to germinate. To understand the molecular mechanisms underlying zygote maturation and the attainment of competence for germination we isolated genomic clones representing three different genes that are specifically expressed in Chlamydomonas reinhardtii zygotes. Accumulation of the RNAs started more than 24 h after mating, setting these genes apart from genes expressed in young zygotes. Upon light-induced germination of zygotes, the mRNAs disappeared. The patterns of RNA accumulation and disappearance were gene specific and suggested a function of these genes in maturation and/or in initial steps of germination. PMID- 1863768 TI - Promoter for a Brassica napus ribulose bisphosphate carboxylase/oxygenase small subunit gene binds multiple nuclear factors and contains a negative-strand open reading frame encoding a putative transmembrane protein. AB - Using a fractionated genomic bank, we have cloned and characterized a Brassica napus gene (rbcSF1) encoding the small sub-unit of ribulose 1,5-bisphosphate carboxylase. The promoter of this gene contains a 29 bp direct repeat capable of forming a single or a double hairpin loop, and three elements that are recognized by leaf nuclear proteins in vitro. The most upstream are the S-box, a small A/T rich sequence between -516 and -512, and the F-box between -492 and -475. Finally, we have also observed binding to the G-box, a regulatory element common to numerous plant promoters. The promoter of rbcSF1 also has a 113 amino acids open reading frame (ORF113) in the non-coding strand. When used to probe a northern blot of leaf RNA, this ORF hybridizes to a 1.5 kb transcript. The protein encoded by ORF113 contains a transmembrane domain. PMID- 1863769 TI - Proteolytic and partial sequencing studies of the bifunctional dihydrofolate reductase-thymidylate synthase from Daucus carota. AB - The bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) of Daucus carota has been further characterized as regards molecular weight, amino acid composition, protease digestion and microsequencing of proteolytic peptides. Data reported in this paper demonstrate that the carrot protein has a calculated Mr of 124,000 thus indicating that, contrarily to what has previously been suggested, it occurs as a dimer of identical subunits. Results of partial amino acid microsequencing show the presence of sequences highly homologous with those of the active sites of both DHFR and TS from other organisms confirming, at the structural level, the bifunctional nature of the carrot protein. As in the case of Leishmania tropica DHFR-TS, incubation of the carrot protein with V8 protease led to a rapid loss of TS activity while retaining that of DHFR. However the pattern of proteolysis did not allow to establish whether the sequence of domains is DHFR-TS as in Leishmania, or vice versa. Low homology of other amino acid sequences, as judged by computer analysis, and absence of common epitopes indicate an apparent divergence between carrot and leishmanian proteins. PMID- 1863770 TI - Promoters of auxin-induced genes from tobacco can lead to auxin-inducible and root tip-specific expression. AB - In previous studies we have identified several mRNAs which accumulate after addition of 2,4-dichlorophenoxyacetic-acid (2,4-D) to auxin-starved tobacco cells. The mRNAs corresponding to cDNA clone pCNT103 were found to accumulate transiently prior to the cell division response due to auxin treatment. In this study we determined the sequences of three 103-like cDNAs and two 103-like genes, GNT1 and GNT35. To further study the regulation of the expression of these genes their 5' regions were translationally fused with the beta-D-glucuronidase reporter gene (GUS). The GNT1 5' region led to GUS expression only in the root tips of transgenic plants. By using transgenic hairy-root cultures and transformed cell suspension cultures it was shown that the 5' regions of both GNT1 and GNT35 lead to 2,4-D-inducible expression of GUS activity. The homology of the 103-like genes with other auxin-regulated genes is evaluated. PMID- 1863771 TI - Alfalfa heat shock genes are differentially expressed during somatic embryogenesis. AB - We have isolated two cDNA clones (Mshsp18-1; Mshsp18-2) from alfalfa (Medicago sativa L.) which encode for small heat shock proteins (HSPs) belonging to the hsp17 subfamily. The predicted amino acid sequences of the two alfalfa proteins are 92% identical and a similar degree of homology (90%) can be detected between Mshsp18-2 and the pea hsp17. In comparison to various members of small HSPs from soybean amino acid sequence similarities of 80-86% were identified. The alfalfa HSPs share a homologous stretch of amino acids in the carboxy terminal region with hsp22, 23, 26 from Drosophila. This region contains the GVLTV motif which is characteristic of several members of small HSPs. At room temperature alfalfa hsp18 mRNAs were not detectable in root and leaf tissues but northern analysis showed a low level of expression in microcallus suspension (MCS). The transcription of Mshsp18 genes is induced by elevated temperature, CdCl2 treatment and osmotic shock in cultured cells. In alfalfa somatic embryos derived from MCS a considerable amount of hsp18 mRNA can be detected during the early embryogenic stages under normal culture conditions. The differential expression of these genes during embryo development suggests a specific functional role for HSPs in plant cells at the time of the developmental switch in vitro. PMID- 1863772 TI - A conserved core structure in the 18-25S rRNA intergenic region from tobacco, Nicotiana rustica. AB - To identify conserved and functionally important features in the intergenic sequences of ribosomal DNAs, the nucleotide sequence of the 18-25S rRNA intergene region in tobacco rDNA was determined and compared to that of other higher plants. Unlike previous comparisons of more diverse organisms, sufficient sequence homology is retained in the higher plants to examine the evolutionary changes which make these regions diverse. Estimates of the secondary structure permit the identification of a 'core-like' structure which appears to maintain the processed sites in close proximity and can be identified in the more divergent sequences. PMID- 1863773 TI - Patterns of gene expression in developing anthers of Brassica napus. AB - The relationship between bud length, anther length and stage of anther development has been investigated in Brassica napus using a series of cytological markers that define steps in the process of male gametogenesis. It was determined that bud length is directly related to anther length and that anther or bud length is tightly linked to the stage of male gametogenesis within the anther. This simple correlation has enabled the construction of cDNA libraries representing transcripts expressed in defined stages of anther development, and the detailed examination of the developmental pattern of expression of anther RNAs. Two anther cDNA libraries were constructed, one from anthers of 1.2-1.8 mm long buds (sporogenesis library) and one from anthers of 1.8-4.0 mm long buds (microspore development library). A total of 19 independent cDNAs have been isolated by differential screening whose temporal expression patterns overlap and which together cover the stages of anther development from pre-meiotic microsporocytes to tri-nucleate pollen grains. The pattern of expression of each of these clones is unique and indicates that stages of anther development which cannot be easily distinguished by light microscopy can be recognised by virtue of the absence or presence of certain RNAs. Three cDNAs isolated from the sporogenesis library have been shown by in situ hybridisation to be tapetum specific. In contrast, five clones isolated from the microspore development library are microspore-specific. These clones exhibit a pattern of expression different to those previously described in that their transcripts are absent in mature pollen grains. Thus these RNAs are probably required in microspore development rather than for the growth of the germinating pollen grain. PMID- 1863774 TI - Analysis of Pteridium ribosomal RNA sequences by rapid direct sequencing. AB - A total of 864 bases from 5 regions interspersed in the 18S and 26S rRNA molecules from various clones of Pteridium covering the general geographical distribution of the genus was analysed using a rapid rRNA sequencing technique. No base difference has been detected amongst the three major lineages, two of which apparently separated before the breakup of the ancient supercontinent, Pangaea. These regions of the rRNA sequences have thus been conserved for at least 160 million years and are here compared with other eukaryotic, especially plant rRNAs. PMID- 1863775 TI - Direct gene transfer into Actinidia deliciosa protoplasts: analysis of transient expression of the CAT gene using TLC autoradiography and a GC-MS-based method. AB - Chloramphenicol acetyl transferase (CAT) gene was used as a reporter gene to assess the conditions for polyethylene glycol (PEG)-mediated transfection of kiwifruit protoplasts. The effect of plasmid concentration and the presence of carrier DNA were each assessed by analysing CAT activity in transfected protoplasts using thin-layer chromatography (TLC) autoradiographic detection of acetylated chloramphenicol. A gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) non-radioactive method was developed for monitoring CAT gene activity. This method provides a high speed of analysis (30 min) and precise means of detecting acetylated products at the nanomolar level, enabling quantification at very low transfection rates. Using this method we optimized plasmid and PEG concentration and also assessed the effect of heat shock on transfection. The best CAT activity was obtained using 30% polyethylene glycol 4000 and by submitting protoplasts to heat shock (45 degrees C, 5 min) prior to transfection. PMID- 1863776 TI - Isolation of a complementary DNA encoding the bean PR4 chitinase: an acidic enzyme with an amino-terminus cysteine-rich domain. AB - The amino acid sequences of peptides generated by trypsin and chymotrypsin digestions of the acidic PR4 chitinase from bean were determined. Oligonucleotide primers derived from this sequence were used to synthesize a PR4 chitinase specific probe by PCR-amplification. This probe allowed the isolation of cDNA clones encoding PR4 chitinase that have been sequenced. This acidic and extracellular chitinase shows some homology to the basic isoform from the same plant, and differs from other known acidic chitinases by the presence of an amino terminal cysteine-rich domain. Southern blot analysis of bean genomic DNA revealed that PR4 chitinase is encoded by a single gene. PMID- 1863777 TI - Nucleotide sequence of a Triticum aestivum cDNA clone which is homologous to the 26 kDa chloroplast-localized heat shock protein gene of maize. PMID- 1863778 TI - Transient expression of beta-glucuronidase in Arabidopsis thaliana leaves and roots and Brassica napus stems using a pneumatic particle gun. AB - Successful transient expression of beta-glucuronidase (GUS) in Arabidopsis thaliana leaves and roots and Brassica napus stems was obtained after gene delivery with a pneumatic particle gun driven by compressed air. Effects of the pneumatic pressure used to accelerate the particles (accelerating pressure; 85 to 200 kg/cm2) and of preculture periods of plant tissues (0 to 6 days) on the efficiency of gene delivery were studied. In A. thaliana leaves, best results were obtained at 115 kg/cm2 of accelerating pressure and 3 days of preculture. In A. thaliana roots, the optimum was at 200 kg/cm2 of accelerating pressure and 3 days of preculture. These results indicate that both preculture period and accelerating pressure are vital factors that determine the efficiency of gene delivery by particle gun. PMID- 1863779 TI - The cDNA sequence of NS1 glycoprotein of Brassica campestris and its homology to S-locus-related glycoproteins of B. oleracea. PMID- 1863780 TI - A Triticum aestivum cDNA clone encoding a low-molecular-weight heat shock protein. PMID- 1863781 TI - An ethylene-responsive flower senescence-related gene from carnation encodes a protein homologous to glutathione S-transferases. AB - Carnation flower petal senescence is associated with the expression of specific senescence-related mRNAs, several of which were previously cloned. The cDNA clone pSR8 represents a transcript which accumulates specifically in senescing flower petals in response to ethylene. Here we report the structural characterization of this cDNA. A second cDNA clone was isolated based on shared sequence homology with pSR8. This clone, pSR8.4, exhibited an overlapping restriction endonuclease map with pSR8 and contained an additional 300 nucleotides. Primer extension analysis revealed the combined cDNAs to be near full-length and the transcript to accumulate in senescing petals. Analysis of the nucleotide sequence of SR8 cDNAs revealed an open reading frame of 220 amino acids sufficient to encode a 25 kDa polypeptide. Comparison of the deduced polypeptide sequence of pSR8 with other peptide sequences revealed significant similarity with glutathione s-transferases from a variety of organisms. The predicted polypeptide sequence shared 44%, 53% and 52% homology with GSTs from maize, Drosophila and man, respectively. We discuss our results in relation to the biochemistry of flower petal senescence and the possible role of glutathione s-transferase in this developmental process. PMID- 1863782 TI - Sequence of a wheat cDNA encoding a pathogen-induced thaumatin-like protein. PMID- 1863783 TI - Nucleotide sequence of a cDNA encoding the putative trypsin inhibitor in potato tuber. PMID- 1863784 TI - A Brassica napus mRNA expressed specifically in developing microspores. AB - The I3 cDNA isolated from a library made from 2-4 mm (immature) anthers of Brassica napus shows microspore-specific expression. Homologous transcripts are detected in buds and anthers of male-fertile plants, but not in green tissues, roots, or in cytoplasmic male-sterile buds. High expression of the transcript is limited to microspores entering and undergoing mitosis. The predicted peptide sequence of the cDNA shows an unusual repeated alanine/proline motif at the C terminus, which may be of importance in the native protein structure. PMID- 1863785 TI - Nucleotide sequence of two cDNAs encoding the adenine nucleotide translocator from Zea mays L. PMID- 1863786 TI - Persistent organochlorine pesticides in blood serum and whole blood. PMID- 1863787 TI - Deposition of esfenvalerate on Brassica vegetables. PMID- 1863788 TI - Contamination of ponds by fenitrothion during forest spraying. PMID- 1863789 TI - Transport of the fungicide chlorothalonil from its operational use on a pond ecosystem. PMID- 1863790 TI - Airborne drift residues collected near apple orchard environments due to application of insecticide mixtures. PMID- 1863791 TI - Pesticide transmission in fabrics: effect of perspiration. PMID- 1863792 TI - Deaths of Canada geese following spraying of turf with diazinon. PMID- 1863793 TI - Planarians in toxicology, standardization of a rapid neurobehavioral toxicity test using phenol in a crossover study. PMID- 1863794 TI - Standard test fish for India and the neighboring countries. PMID- 1863795 TI - Enhancement of hepatocarcinogenesis in rainbow trout with carbon tetrachloride. PMID- 1863796 TI - Heavy metal bioaccumulation in lamb and sheep bred in smelting and mining areas of S.W. Sardinia (Italy). PMID- 1863797 TI - Sequestration of copper and zinc in the hepatopancreas of Armadillidium vulgare latreille following exposure to lead. PMID- 1863798 TI - Concentration of metals in various larval stages of four Ephemeroptera species. PMID- 1863799 TI - Toxicity of metals to a freshwater tubificid worm, Tubifex tubifex (Muller). PMID- 1863800 TI - Assessment of mercury toxicity by the changes in oxygen consumption and ion levels in the freshwater snail, Pila globosa, and the mussel, Lamellidens marginalis. PMID- 1863801 TI - Short-term oral administration of several manganese compounds in mice: physiological and behavioral alterations caused by different forms of manganese. PMID- 1863802 TI - In vitro and in vivo responses of rat tissues to cadmium-induced lipid peroxidation. PMID- 1863803 TI - Acute effects of benzene and cyclophosphamide exposure on cellular and humoral immunity of cotton rats, Sigmodon hispidus. PMID- 1863804 TI - High performance liquid chromatography as a tool in the definition of abnormalities in monoamine and tryptophan metabolites in cerebrospinal fluid from patients with neurological disorders. AB - In this study we report the levels of 3-methoxy-4-hydroxyphenylglycol, 3,4 dihydroxyphenylacetic acid, homovallinic acid, tryptophan, 5-hydroxyindole-3 acetic acid and serotonin in lumbar cerebrospinal fluid (CSF) from patients with multiple sclerosis, cerebrovascular disease and muscular tension headache the later, as healthy controls. The separation of these substances was performed on a reversed phase column by ion pair high performance liquid chromatography and detection was made by a glassy carbon electrode set at +900 mV vs Ag+/AgCl. The whole separation was achieved within 25 min. Concentrations of all substances (10 1000 pmole/L) were linearly proportional to areas obtained. The system is sensitive, stable and reproducible. The significance of CSF levels of these metabolites from patients groups compared with healthy controls are discussed. PMID- 1863805 TI - Chromatographic techniques in inborn errors of metabolism. AB - Chromatography has played a pivotal role in the advances made during the last 30 years in our knowledge of inborn errors of metabolism. This review discusses the application of some of these techniques to the analysis of organic acids and acylcarnitines. The separation of organic acids needed a comprehensive approach that would permit all of the many organic acids present in urine or other complex mixtures to be extracted, analysed and identified in a single run. This required analytical methods of great resolving power, wide linear range and universal detectors such as gas chromatography (GC), or GC coupled with mass spectrometry. Sample preparation was another problem that has been tackled by a variety of approaches. Organic solvents have been employed widely for the extraction of organic acids from physiological fluids. Unfortunately, recoveries of the different organic acids by this method are sometimes less than quantitative and variable depending on the compound. Other methods, such as the use of DEAE Sephadex columns, have the advantage of resulting in close to 100% recoveries, but are more tedious. Liquid partition chromatography on short silicic acid columns has also been recommended as a useful clean-up step prior to GC, permitting both the identification and quantitation of organic acids in urine, plasma or amniotic fluid. Although many derivatization procedure have been used to prepare organic acids for gas chromatography, the most common is trimethylsilylation. Oxo acids are usually reacted with one of several commonly used reagents to form oximes. GC analysis of organic acids was initially done using packed columns with methylsilicone-based, non-polar stationary phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863806 TI - Application of ion pair high performance liquid chromatography to the analysis of porphyrins in clinical samples. AB - Reversed phase ion pair chromatography is a highly selective separation technique for the determination of free porphyrin carboxylic acids from human materials. Isocratic and gradient elution methods can be used to analyse porphyrin isomers and to establish porphyrin profiles for the biochemical diagnosis of porphyrias. Ion pair high performance liquid chromatography led to the discovery of the atypical isomers II and IV of uroporphyrin and coproporphyrin in human urine. Advantages and limitations of the ion pair technique are discussed. PMID- 1863807 TI - Biomedical applications of chiral liquid chromatography. AB - Many drugs are racemic and therefore much effort has to be devoted towards the stereoselective synthesis of the most effective or less harmful component of a racemic mixture. High performance liquid chromatography will play an important role in the clinical analysis of racemic drugs in anticipation of regulations that are currently being discussed and are expected to be enforced by the end of this decade. In this review a number of methods for chiral resolution are outlined. These include the formation of diastereoisomers and the use of chiral stationary phases or chiral mobile phase additives. PMID- 1863808 TI - Field flow fractionation in biomedical analysis. AB - Samples of biomedical interest which have been analysed by field-flow fractionation techniques are surveyed. The list begins with whole cells and microorganisms, going through viruses, nucleic acids, cell fragments and organelles, down to proteins and their aggregates. The principles of separation in the normal and steric mode of retention are illustrated, and instrumentation and techniques are described. The review concentrates mainly on the two systems of choice for biomedical applications: sedimentation and flow field-flow fractionation. PMID- 1863809 TI - Contribution of marrow stromal cells to the regulation of osteoblast proliferation in rats: evidence for the involvement of insulin-like growth factors. AB - Fibroblast-like marrow stromal cells are believed to play a role in the maintenance of osteoblast populations at the marrow-bone interface. We now report that this interaction may be very specific. Stromal cell conditioned medium (SC CM) stimulated DNA synthesis and proliferation in culture of neonatal rat calvarial osteoblasts at low concentrations (1.25-5%), but was inhibitory at 10%. At growth promoting effective concentrations, the activity of osteoblast alkaline phosphatase was decreased. This action was selective since SC-CM failed to promote the growth of rat calvarial fibroblasts. Characterization of the SC-CM indicated the cells produced IGF-I and -II and a wide range of molecular weight fractions with putative stimulatory action (FPLC analysis using Superose 12 and 6 gel permeation columns). HPAE-PAD analysis showed that some elements were glycosylated, and the composition suggested the presence of N- and O-linked oligosaccharide chains. Because rat marrow stromal fibroblast-like cells produce a number of osteotropic factors which affect calvarial osteoblast growth, these interactions may be important to considerations about the etiology of the osteoporoses. PMID- 1863810 TI - A new set of calibration standards for estimating the fat and mineral content of vertebrae via dual energy QCT. AB - A new set of calibration standards has been developed for implementing a dual energy (DE) quantitative CT technique for estimating the fat and bone content of vertebrae. The QCT technique is based upon a three-component model of bone and utilizes calibration materials that mimic those components in their X-ray attenuation properties. The three components we chose to simulate are bone (mineral plus collagen), fat and a fat-free red marrow. This choice was predicated upon our desire to employ materials that would facilitate later experimental verification of the method. The calibration standards and a set of test samples were manufactured of tissue-simulating epoxy resins. They were employed in studies of the accuracy (consistency) and precision of the technique and in a study of 21 normal postmenopausal women. Estimates of the bone and fat content of the test samples were consistent with the manufacturer's specifications to within 13 mg/ml and 7 vol%, respectively. Long-term reproducibility (coefficient of variation) for both quantities was about 3%. The average bone content of the T12-L3 vertebrae of the human subjects was 262 +/- 32 mg/ml (152 +/- 18 mg/ml calcium hydroxyapatite or mineral) and the average fat content was 63 +/- 8%. Conventional single energy (SE) QCT measurements of these vertebrae were about 23% less than the DE mineral measurements, which is consistent with the differences between SEQCT and ash content that others have determined via chemical analysis. The DE fat content is, in absolute terms, about 15% greater than values reported in the literature and may be due to an error in the assumed composition of red marrow. The true accuracy of the bone and fat estimates is to be determined in a planned human vertebral specimen study. PMID- 1863811 TI - Differential regulation of the 55 and 44 kDa forms of secreted phosphoprotein 1 (SPP-1, osteopontin) in normal and transformed rat bone cells by osteotropic hormones, growth factors and a tumor promoter. AB - Confluent cultures of rat bone cells synthesize several forms of secreted phosphoprotein 1 (SPP-1, osteopontin), the major phosphorylated forms of which migrate at 55 and 44 kDa on 15% cross-linked SDS-PAGE gels and correspond to the transformation-associated proteins pp 69 and pp 62. A clonal rat calvarial cell line (RCA 11), which expressed the highest level of SPP-1, produced only the 55 kDa form of the phosphorylated protein, whereas normal rat calvarial cells enriched in osteoblastic cells (RC IV cells) produced mostly the 55 kDa form, with small amounts of the 44 kDa form. In contrast, a 44 kDa form was the major [32PO4]-labelled SPP-1 synthesized by a rat osteocarcoma cell line (ROS 17/2.8 cells) with lesser amounts of the 55 kDa SPP-1. When [35S]methionine was used to measure protein synthesis, only the 55 kDa SPP-1 could be clearly detected in confluent cultures of each cell population, indicating that the 55 kDa SPP-1 is the prominent form of SPP-1 synthesized by each cell population. Following treatment of the normal rat bone cells for 24 h with osteotropic hormones (vit D3, PTH and RA), growth factors (PDGF, EGF, TGF-beta), a tumor promoter (TPA) and a plant lectin (Con A), the 55 kDa [35S]methionine labelled SPP-1 was increased 1.7-8.3-fold. Similar, but generally lower responses were observed in the clonal RCA 11 cell line, whereas the ROS 17/2.8 cells were more refractory, showing only a strong response to vit D3. In general, vit D3 produced the strongest stimulation in all populations with TGF-beta producing a good response in the non transformed cells and RA in the RC IV cells. In contrast, PTH was inhibitory in both RCA 11 and ROS 17/2.8 cells. In most, but not all, cases the alteration in SPP-1 synthesis reflected similar changes in SPP-1 mRNA and in the intensity of the [32PO4]-labelled 55 kDa SPP-1. Collectively, these studies demonstrate that bone cells produce several forms of SPP-1 which are differentially regulated in normal and transformed cells through both transcriptional and posttranscriptional mechanisms. PMID- 1863812 TI - Autocatalytic membrane conductance and memory. AB - A basic characteristic of biological memory is that it has a graded duration, which, even for so-called short-term memory, can vary from minutes to days (i.e. over about three orders of magnitude), depending on the training protocol, which one can think of as determining the "strength" of the memory. Furthermore, the molecular analysis of simple learning in invertebrates has revealed many examples where "learning" is produced by a decrease in an appropriate membrane conductance. This paper provides a quantitative analysis of a simple kinetic scheme whereby a conductance decrease can be produced by repetitive nerve impulses, with a duration that varies with stimulus frequency. The simplest model considered is based on the actual kinetics of the naturally-occurring ionophore Monazomycin. This model yields durations ranging only over a factor of about 10, for reasonable parameter values. However, a simple modification of the model yields memory durations ranging over three or more orders of magnitude. We also show that Monazomycin-like kinetics can appear as the result of a combination of simple uni- and bi-molecular reactions, thus making more plausible the possibility that the effects described here may operate in actual biological systems. PMID- 1863813 TI - The statistical correlation of nucleotides in protein-coding DNA sequences. AB - The statistical correlation of nucleotides in a DNA sequence is described by a set of redundancies D1, D2, D3, . . . . By calculation of [Dn] of 2341 coding regions of nucleic acid sequences it is demonstrated that about 2/3 of sequences has correlation length less than or equal to 2, 10% of sequences--correlation with 3-periodicity and others--long range aperiodic correlations. The implications of the results from the interactions of random mutation and natural selection are discussed briefly. PMID- 1863814 TI - A generalized tapering equivalent cable model for dendritic neurons. AB - A mathematical model has been developed which collapses a dendritic neuron of complex geometry into a single electrotonically tapering equivalent cable. The modified cable equation governing the transient distribution of subthreshold membrane potential in a branching tree is transformed, becoming amenable to analytic solution. This transformation results in a Riccati differential equation whose six solutions (expressed in terms of elementary functions) control the amount and degree of taper found in the equivalent cable model. To illustrate the theory, an analytic solution (in series form) of the modified cable equation is obtained for a voltage-clamp present at the soma of a quadratically tapering equivalent cable whose distal end is sealed. PMID- 1863815 TI - Visual discrimination learning in binocularly deprived cats: 20 years of studies in the Nencki Institute. AB - Data obtained by the author and his colleagues on various forms of visual discrimination learning in cats binocularly deprived of pattern vision with cloth masks (BD cats) are reviewed. In these studies two comparison groups were used: controls reared also in the laboratory but with open eyes (C cats) and cats reared in normal environment outside the laboratory (N cats). Data from other laboratories on lid-sutured and dark-reared BD cats are also shortly reviewed. The BD cats showed several clear-cut deficits. Those in pattern discrimination and in fine contrast discrimination were presumably mainly due to impairment of the perceptual inhibitory learning, whereas those in coping with the partition in the apparatus and in successive discrimination were due to impairment of associative inhibitory learning. The deficits in object discrimination and in interocular transfer were apparently due to a reduced number of binocular neurons in the deprived visual cortex and superior colliculi. Dramatic deficit in relearning after ablation of the superior colliculi-pretectum complex shows a reduced utilization of the abnormal cortex in discrimination learning. The C cats shared fully with BD cats a dramatic impairment in the visually delayed response. This short-term memory deficit was presumably due to a limited practice in visual learning in cage-reared cats. The C cats showed also some impairment in coping with the partition and in relearning after the colliculus-pretectum ablation. The BD cats were not impaired in pattern vs. no-pattern discrimination and in grating discrimination. Thus, visual deprivation does not impair the formation of excitatory and simple inhibitory connections required in crude discrimination. Moreover, presumably due to their less distractibility by external stimuli, the BD cats could be even superior to N and C cats in very crude discrimination tasks. PMID- 1863816 TI - Identification of the Purkinje cell/climbing fiber zone and its target neurons responsible for eye-movement control by the cerebellar flocculus. AB - We identified 3 Purkinje cell/climbing fiber zones in the cat cerebellar flocculus. The zones were perpendicular to the long axes of the crooked floccular folia, forming the crooked zones. Each zone was different in axonal projection areas of its target neurons. From the neuronal networks it is theoretically expected that activity changes of a particular zone control eye movement in a particular plane: (1) the rostral and caudal zones on one side control movement in the anterior canal plane on the side of the activity changes and those on both sides control movement in all vertical planes from sagittal to transverse planes; and (2) the middle zone controls movement in the horizontal plane by reciprocal activity changes on both sides. The zone-specific climbing fiber input to a particular zone may contribute to activity changes of the zone in response to mossy fiber input spreading across several zones. Electrical stimulation of each zone evoked the same pattern of eye movement as that theoretically expected from the neuronal networks. This is the first indication that there are indeed functional differences between the Purkinje cell zones in the cerebellum. Our findings support Oscarsson's proposal that each Purkinje cell/climbing fiber zone plus its target neurons may be an operational unit for control of a given motor function. PMID- 1863817 TI - Why early arthritis clinics? PMID- 1863818 TI - Metalloproteinase inhibitors--crystal gazing for a future therapy? PMID- 1863819 TI - Psoriatic arthritis (PA): a clinical, immunological and radiological study of 180 patients. AB - We carried out a prospective study of the clinical, laboratory and radiological features of 180 patients with psoriatic arthritis. We initially classified our patients into five groups as described in the publications of Moll and Wright. Thirty-seven per cent had oligoarthritis, 36% polyarthritis, 23% spondarthritis (sacroiliitis and/or spondylitis) and 4% had the mutilans form. The distal joint arthritis type did not exist as an entity and the distal interphalangeal (DIP) joints were affected in all groups. The spondarthritis form includes patients with exclusively axial manifestations and also those who in addition have peripheral arthritis (oligoarthritis, polyarthritis, DIP arthritis). Only 53% of our patients had nail involvement. We found an increase of IgA levels in patients with axial disease. This suggests a relationship between ankylosing spondylitis and psoriatic spondylitis. The HLA-B17/Cw6 association increased in the oligoarticular form. The increase of antigen B17 correlated with the spondarthritic and oligoarthritis forms whereas Cw6 was more important in the oligoarthritis form. An increase of the HLA-B27/Cw1 association and the spondarthritic form was also found. Moreover, we detected a greater incidence of the HLA-B27 antigen in patients with bilateral sacroiliitis (85%) than in patients with unilateral sacroiliitis (22%). Our work revealed that PA is not a harmless disease; 57% of our patients had erosive arthritis while 19% had ARA class III or IV functional impairment. PMID- 1863820 TI - Predictors of the long-term outcome of early synovitis: a 5-year follow-up study. AB - One hundred patients who presented to an Early Synovitis Clinic in 1979-81 were called for review after a minimum of 5 years. Sufficient data for analysis were obtained in 88 cases, of whom 36 had a final diagnosis of rheumatoid arthritis (19 seropositive, 17 seronegative) and 16 human parvovirus B19 arthropathy. Outcome was assessed by persistence of symptoms greater than 24 months and functional disability by Health Assessment Questionnaire. Sixty-two patients had persistent disease, with 26 showing some functional impairment (positive HAQ FDI). A number of presenting features were assessed for their ability to predict outcome at 5 years. Polyarticular onset of disease was associated with a poor prognosis but lacked both specificity and sensitivity. Certain laboratory tests at presentation, including positive rheumatoid factor and low serum sulphydryl levels, also indicated a poor outcome. Combining these serological abnormalities gave 100% specificity for detecting persistent, disabling disease but with rather low sensitivity. Thus, other test systems are required to increase further the successful prediction of clinical outcome in patients with early synovitis. PMID- 1863821 TI - Evidence for impaired erythropoietin response to anaemia in rheumatoid disease. AB - In this study we determined the serum erythropoietin (Epo) levels of 97 anaemic rheumatoid (RD) patients (Hb less than 11 g/dl) of whom 44 had serum ferritin greater than 60 micrograms/l (anaemia of chronic disorders; ACD), 26 had ferritin 20-60 micrograms/l and 27 had ferritin less than 20 micrograms/l. These results were compared with the Epo levels of 36 iron deficient controls (Hb less than 11 g/dl), 33 non-anaemic RD patients and 33 normals. The serum Epo levels of anaemic subjects were significantly higher (P less than 0.05) than those of non-anaemic patients. Despite similar Hb, the Epo results (geometric mean (confidence limits] of the ACD group (38 (32,45) mU/ml) and of RD patients with ferritin of 20-60 micrograms/l (39 (33,46)mU/ml) were significantly lower (P less than 0.05) than those of iron deficient controls (65 (52,80)mU/ml). When the Hb fell to 10 g/dl or less, the serum Epo of 13 RD patients with ferritin less than 20 micrograms/l was 65 (47,89)mU/ml, significantly lower (P less than 0.05) than that of 17 iron deficient controls (104 (78,136)mU/ml). These results justify clinical trials of recombinant human Epo in RD patients with ACD. PMID- 1863822 TI - Role of TNF alpha, in relation to IL-1 and IL-6 in the proteoglycan turnover of human articular cartilage. AB - In both young and old human articular cartilage explants, TNF alpha induced a concentration-dependent, reversible suppression of the proteoglycan (PG) synthesis. Young cartilage was more sensitive to TNF alpha than old cartilage: 50% suppression of PG synthesis was reached at a TNF alpha concentration of 5 U/ml for young and 30 U/ml for old cartilage, whereas at 10(3) U/ml the PG synthesis of young cartilage was blocked and that of old cartilage suppressed by 80%. These inhibition levels of PG synthesis resulted in 25% PG depletion of the explants after 8 days of culture. The release of cartilage PG was not enhanced. TNF alpha induced no detectable amounts of IL-1 (less than 0.01 U) in young or old cartilage but did induce IL-6 production. The induced amounts of IL-6 were higher in young than in old cartilage but no dose-dependency was evident. Antibodies to neither IL-1 nor IL-6 had any influence on the TNF alpha-induced suppression of PG synthesis. The combination of TNF alpha and IL-1 led to an additive inhibition of PG synthesis which had no relationship to induced IL-6. TNF alpha was about 100-fold less active than IL-1. PMID- 1863823 TI - A limited association of generalized osteoarthritis with alleles at the type II collagen locus: COL2A1. AB - A significant genetic influence in osteoarthritis has been observed in the combination of Heberden's nodes and generalized osteoarthritis. We examined whether mutation in the gene encoding the major cartilage matrix protein type II collagen was responsible by comparing allele frequencies at the locus (COL2A1) in a group of 61 patients with nodal GOA with a control population and by analysing the COL2A1 genotypes of 21 affected sibling pairs. There were no significant allele differences but a slightly increased tendency over chance alone for affected siblings to have inherited the same COL2A1 alleles from their parents. PMID- 1863824 TI - Oestrogen, the prevention of bone loss and osteoporosis. AB - There is overwhelming evidence that oestrogen can prevent bone loss and there is less good but convincing evidence that oestrogen prevents fractures. Oestrogen use of between 5 and 10 years is associated with a 50% reduction in risk of fracture. There is good evidence that in established osteoporosis, oestrogen prevents further bone loss and reduces the incidence of fractures. Oestrogen use leads to lasting skeletal benefits and will prevent bone loss at whatever age it is started. Prior to fracture there are no symptoms associated with osteoporosis and few patients will be diagnosed at a time when effective treatment could be instigated. It is apparent that the risk of developing osteoporosis cannot be deduced from clinical data alone and bone mineral measurements provide the single best test for future risk. Bone mass can be measured directly and there is no need for guess work. The most important potential application for oestrogen is in preventive therapy, and the efficient use of oestrogen in this situation depends upon the diagnosis of low bone mass. Who to treat remains the issue. For any age group the median value of bone density and a range of percentiles can be generated, thus facilitating therapeutic decisions. PMID- 1863825 TI - Which patients see a rheumatologist? SWRACR (South Western Regional Advisory Committee on Rheumatology). AB - Rheumatology outpatient consultations were recorded throughout the South Western Regional Health Authority for one month. Of 2987 consultations (equivalent to 32,600 annually), 630 (21%) were new referrals who waited 60 days (mode) before their consultation. Rheumatoid arthritis and polyarthritis accounted for 43% of new referrals and 75% of follow-up patients. For these categories, 6.5 follow-up patients were seen for each new referral, but this ratio varied from 3.7 to 11.7. Other diagnoses also had variable patterns of follow-up but because they represented only a small proportion they were less relevant to overall service provision and resource consumption. These data not only outline current outpatient working patterns but also indicate areas of further investigation which might elucidate methods of providing good patient care and appropriate use of resources. PMID- 1863826 TI - Review of UK data on the rheumatic diseases--8. SLE. PMID- 1863827 TI - The use of nasal calcitonin in the treatment of post-traumatic algodystrophy. AB - Calcitonin is widely used in the treatment of algodystrophy but a major disadvantage is the need for its parenteral administration. For this reason, we evaluated the effect of 400 iu of nasal calcitonin in the treatment of post traumatic algodystrophy in a prospective randomized double-blind study. We found no demonstrable effect on the clinical or skeletal progression of the disorder using sensitive methods of measuring the response to treatment. There was, however, a small but significant hypocalcaemic response in the treatment group despite no change in the other indices of bone turnover. Possible reasons for this lack of clinical and skeletal effect are discussed. PMID- 1863828 TI - Plasma levels of interleukin-1-alpha in rheumatoid arthritis. AB - Interleukin-1-beta (IL-1 beta) has been implicated as an inflammatory mediator in rheumatoid arthritis (RA) but little is known about the related cytokine, IL-1 alpha, in this disease. IL-1 alpha has biological properties similar to IL-1 beta but, unlike IL-1 beta, remains mostly cell-associated. In this study plasma IL-1 alpha was measured by radioimmunoassay in patients with RA and in healthy controls. Plasma levels were compared with conventional measures of disease activity. The mean levels in the two groups were not significantly different and, within the patient group (n = 53), the only significant cross-sectional correlation was between plasma IL-1 alpha and ESR. In longitudinal studies, some individual patients had plasma IL-1 alpha levels that correlated with different measures of disease activity. We conclude that while IL-1 alpha may be involved in the immunopathogenesis of RA, its measurement in plasma seems to offer little of clinical value. PMID- 1863829 TI - A comparison of disability measured by the Stanford Health Assessment Questionnaire disability scales (HAQ) in male and female rheumatoid outpatients. AB - Eighty-five consecutive rheumatoid patients (M:F = 22:63) seen during a 10-week period were studied. There were significant differences between the sexes for haemoglobin (means (SD) M = 13.5 (1.2), F = 12.0 (1.6) g/dl, P less than 0.01), presence of nodules (M = 50%, F = 19%, P less than 0.05) and for the HAQ scores (mean (SD) score M = 1.1 (0.9), F = 1.7 (0.9), P = 0.03) but not for age, disease duration, presence of erosions, Larsen score, treatment, pain, early morning stiffness, articular index, ESR, and C-reactive protein. The results suggest that the patients were matched for age, disease activity, severity and duration. The difference in haemoglobin between the sexes is in keeping with a reference population. The data suggest that the impact of RA has a greater effect on the functional status of women. PMID- 1863830 TI - Aplastic anaemia in systemic lupus erythematosus: a cellular immune mechanism? AB - Aplastic anaemia is a rare complication of systemic lupus erythematosus (SLE). The mechanism is unclear but is thought to be related to an autoantibody to bone marrow precursors of haematopoiesis. We report a case of SLE related aplastic anaemia in which therapy with methylprednisolone and high dose cyclophosphamide followed by prednisolone and azathioprine resulted in complete clinical and haematological remission. Bone marrow cultures showed inhibition of erythropoiesis when incubated with acute and remission serum. Myeloid colony growth was not affected by either serum. The serum inhibitor we demonstrated was only active in vitro, and we postulate that the mechanism for marrow aplasia may have been an autoimmune cellular process. PMID- 1863831 TI - Non-infective verrucous endocarditis in a patient with 'primary' antiphospholipid syndrome. AB - A 27-year-old women with 'primary' antiphospholipid syndrome, who developed a haemodynamically significant non-infective verrucous endocarditis is reported. Her mother suffered from antiphospholipid syndrome associated with systemic lupus erythematosus. A pathogenetic role of antiphospholipid antibodies in heart valve lesions is suggested. PMID- 1863832 TI - Combination therapy in rheumatoid arthritis. PMID- 1863833 TI - Severe lupus crisis with agranulocytosis and anuric renal failure due to a mesangial lesion (WHO IIB)--successful treatment with cyclophosphamide pulse followed by plasmapheresis. PMID- 1863834 TI - Can exercise prevent osteoporosis? PMID- 1863835 TI - Recovery of anterior spinal artery syndrome in a patient with systemic lupus erythematosus and antiphospholipid antibodies. PMID- 1863836 TI - Rheumatology manpower in Australia. PMID- 1863837 TI - Successful treatment of Raynaud's phenomenon with limaprost, an oral prostaglandin E1 analogue. PMID- 1863838 TI - Detection of cartilage degradation with sodium NMR. PMID- 1863839 TI - What do patients and rheumatologists regard as an 'acceptable' risk in the treatment of rheumatic disease? PMID- 1863840 TI - Osteoporosis and ankylosing spondylitis. PMID- 1863841 TI - The utility of the 1987 revised ARA criteria for rheumatoid arthritis in early synovitis. PMID- 1863842 TI - Genetics of rheumatoid arthritis. PMID- 1863843 TI - Regulation of gene expression. AB - A fundamental tenet of biology is that the phenotype of an organism is ultimately determined by its complement of genes. In multicellular organisms, it is the regulated pattern of expression of genes which determines the proliferation and differentiation of individual cell lineages and hence establishes the adult phenotype. It is therefore no surprise that both neoplasia and many developmental pathologies involve lesions in the regulation of specific genes. For this reason, an understanding of how genes are regulated has become an area of intense interest in both medicine and biology. PMID- 1863844 TI - Recessive oncogenes, antioncogenes and tumour suppression. AB - Oncogenesis results from an accumulation of genetic mutations in a single cell. Mutations may result in the cell acquiring new functions or losing specific functions required for normal growth control. Evidence for the latter may be adduced from the results of fusing tumour and normal cells to form somatic cell hybrids, and from studies of allele loss in a number of human tumours. The locations the critical genes have been discerned in some cancer predisposition syndromes either by observations of consistent cytogenetic abnormalities, or by genetic linkage studies, or both. Genes whose inactivation is important in the genesis of retinoblastoma, Wilms' tumour and colorectal cancer have been identified and cloned. Their normal functions include control of transcription and cell-cell interactions. In the case of retinoblastoma, the interaction between the normal gene product and that of the transforming genes of a number of oncogenic DNA viruses has been delineated. Identification of 'tumour suppressor' genes has not only improved understanding of the process of oncogenesis, but may also aid in the presymptomatic detection of mutant gene carriers. PMID- 1863845 TI - Cancer metastasis. AB - The process of metastasis consists of a series of linked, sequential steps that must be completed by tumour cells if a metastasis is to develop. Although some of the steps in this process contain stochastic elements, metastasis as a whole favors the survival and growth of a few subpopulations of tumour cells that pre exist within the heterogeneous parent neoplasm. Metastases can have a clonal origin, and different metastases can originate from the proliferation of single cells. The outcome of metastasis depends on the interaction of metastatic cells with different organ environments. Organ-specific metastases have been demonstrated in a variety of experimental tumour systems, and tumour growth can be specific to a particular site within one organ. The factors that regulate metastasis are the intrinsic properties of some tumour cells and host factors involved in homeostasis. Understanding these factors should allow for the development of more effective treatment of cancer metastasis. PMID- 1863846 TI - Immune modulation and cancer. AB - The concept that the immune system is involved in defence against cancer goes back nearly a hundred years. Despite increased sophistication in our analysis of the immune response it has proven difficult to demonstrate a powerful role of the immune system in either the prevention or treatment of cancer. Animal data has consistently and clearly shown that the immune system can identify and reject experimental tumours. In patients the data is more conflicting. The isolation of individual cytokines which stimulate specific components of the immune response and have a anti-cancer effect does suggest, however, that as we learn more about the interaction between immunity and cancer, novel methods for the diagnosis and therapy of cancer will be developed. PMID- 1863847 TI - Carcinogenesis: molecular defences against carcinogens. AB - It has long been recognized that exposure to specific chemical and physical agents can result in the appearance of tumours in both man and animals. There is substantial evidence that DNA is the ultimate cellular target of carcinogens and that DNA repair is an important cellular defence against the effects of carcinogen exposure. Some insight into the molecular processes involved in cellular responses to carcinogens is provided by the occurrence of rare human disorders that display complex abnormalities in processing DNA damage or maintaining genomic integrity. These disorders include xeroderma pigmentosum, Cockayne syndrome, ataxia telangiectasia, dysplastic nevus syndrome and Bloom syndrome. Such disorders have provided clues to some of the basic mechanisms involved in carcinogenesis. PMID- 1863848 TI - Tumour growth dynamics. AB - Tumour growth has been shown to approximate to the exponential in human cancers and, in general, the doubling times range from weeks to months. In contrast, the replicative processes at the cellular level, the cell cycle is completed within a time interval of a few tenths of hours in the majority of cell types. This discrepancy is due to cell loss within the tumour and a growth fraction of less than unity. In normal tissues a steady state renewal system operates, which contains the enormous proliferative potential and tumour growth is a manifestation of a breakdown of normal regulatory feedback mechanisms. Techniques are now available which can quantitate the rate constant for cell production in human tumours and these measurements are being used to design specific treatment for special tumours. PMID- 1863849 TI - Genes and cancer. AB - Cancer can be considered a genetic disorder of somatic cells. Strong evidence comes from several areas: (1) chromosomal analysis reveals cancer cells have abnormal karyotypes; (2) some inherited syndromes are associated with an increased risk of cancer and for others, cancer itself occurs as an inherited trait; (3) cells can become malignant by a variety of agents that damage DNA, and (4) some types of viruses can induce tumours. One common thread has been the normal cellular sequences transduced by viruses and mutated to become oncogenic (oncogenes) are the same sequences to become activated by nonviral mechanisms. These oncogenes appear involved in cell proliferation and/or differentiation and their products apparently function in the signal transduction pathway from the cell exterior to the nucleus. In addition, evidence from familial studies indicate mutations associated with gene inactivation or loss of function are also important in the aetiology of tumour formation. These genes, termed tumour suppressor genes, seem to be involved in the negative control of cellular proliferation. Cancer is a multistep process and it is now becoming clear that the different stages involve genetic alterations in both oncogenes and tumour suppressor genes. PMID- 1863850 TI - Regulation of c-fos expression in Swiss 3T3 cells: an interplay of multiple signal transduction pathways. AB - The mitogenic response of Swiss 3T3 cells is regulated by synergistic interactions between multiple signal transduction pathways. Among the earliest nuclear signals in quiescent cells stimulated to divide is a dramatic increase in the expression of the c-fos proto-oncogene. The regulation of c-fos expression itself is a complex process involving several upstream enhancer elements which dictate the transcriptional response to specific intracellular signals. Here, we review our studies concerning the effects of defined molecular signals, alone or in combination, on c-fos mRNA levels in Swiss 3T3 cells. We propose that cell proliferation requires the cooperative interaction of distinct signalling pathways and that in this context c-fos induction plays a regulatory role in mitogenesis. PMID- 1863851 TI - Prevalence of aberrant expression of the epidermal growth factor receptor in human cancers. AB - This chapter reviews briefly the prevalence of overexpression of the epidermal growth factor receptor in human cancers. In addition, it examines the mechanisms responsible for increased expression and its clinical significance. PMID- 1863852 TI - [Demographic trends and the burden of cardiovascular diseases]. AB - The current burden of cardiovascular disease in the U.S. population and recent trends in morbidity, mortality and risk factors provide a perspective on heart disease in the 21st century. Projections of demographic trends for populations and predictions of the frequency, distribution and characteristics of cardiovascular disease in the future are offered with numerous reservations and subject to revision. Nonetheless, we can expect to see more patients with cardiovascular disease in the next few decades and these patients are likely to be older and to be from the less well-educated and poorer socioeconomic segments of society. Improvements in treatment for the initial cardiovascular event may result in increased survival of women and men suffering permanent damage or disability. There will also be better opportunities to prevent cardiovascular diseases through modifying risk factors in the general population and in high risk individuals. Non-invasive procedures will also increase opportunities for detecting and reversing preclinical atherosclerosis through hygienic and therapeutic measures. PMID- 1863853 TI - [Address of Mr. Rene Truhaut, president for 1991]. PMID- 1863854 TI - [Criteria of brain death]. AB - Authors have previously published April 1988 a lecture where they criticize the bad denomination "passed coma" full of ambiguity for public mind, to which "brain death" ought to be preferred. In the present communication, they remark that this last denomination is not absolutely exact because the real site of responsibility of death is the "brain stem", or to say better the medulla. They discuss of some explorative tests of this part of the encephalon. PMID- 1863855 TI - [Principles and first results of the European program of breast cancer screening in the Bas-Rhin]. AB - A mammographic breast cancer screening began in May 1989 in the Bas-Rhin. It has been selected by "Europe against Cancer" for France. Its aim is not to prove the efficiency of mammography screening by one view every two years, as many studies has proven it. Its purpose is to find the best methodological model for a national campaign. Its principles are to change attitudes and to obtain the active participation of the physicians without creating new structures. This campaign is offered to women aged 50 to 65, living in Bas-Rhin (74,200 women) without individual convocations. Their participation is obtained by a continuous information and motivation. The mammographic examinations are taken in charge by the Health Insurance and performed by the radiologists who have signed a convention. The homogeneity of the results is assured by a double and triple reading under the responsibility of the ADEMAS. In May 1990, after one year, 17,228 women had presented to the screening test. The positive test rate is 7.6% and 7.6% of the women had a diagnostic procedure which indicated a biopsy for 188 women. Among the first 176 histological results, 76 cancers have been diagnosed, 100 women had a benign lesion. The ratio cancer/benign lesion is 0.76. PMID- 1863856 TI - [Pilot hospitals: hope for improving the control of nosocomial infections]. AB - Nosocomial infections are both poorly studied and quantified (between 3.68% to 21% depending on the author). Not only do they seriously affect patients but they are also extremely expensive both in direct and indirect costs as shown by actual cases. To prevent these infections efficiently, hospitals have to continuously monitor nosocomial infections within their departments, thus providing at any time, information about the primordial factors and enabling early stage intervention and the interruption of the "contamination-infection" chain. The Recommendations of the Council of Europe, in particular Recommendation R(84)20, have enabled this to be put into practice: the departments of 35 pilot hospitals have decided to declare their nosocomial infections, recording and processing their data with the same software; global processing is provided free of charge by the International Association for Hospital Hygiene Research. Six months after the start of the operation, the first conclusions are highly positive with 2794 notification forms received (a very good answer rate) showing in particular that more than 50% of nosocomial infections are due to three main entry points [urinary catheter (26%), intubation (13.3%), natural cavities (11.2%)] and three predominant germs [Staphylococcus aureus (22%), Escherichia coli (18.9%), Pseudomonas aeruginosa (11.9%)]. PMID- 1863857 TI - [Results and contributing prospects of molecular probes and genetic amplification in vitro (PCR) in toxoplasmosis]. AB - Toxoplasmosis is one of the latest parasitic diseases to have benefited from molecular biological study (1989). To our knowledge we were one of the first to have cloned several DNA probes using genomic DNA from Toxoplasma gondii. One of these probes, TGR1E, has been sequenced and has enabled the selection and chemical synthesis of 4 oligonucleotides (22 to 25 nucleotides respectively) for use in the Polymerase Chain reaction (PCR). Completely specific for Toxoplasma gondii, they confer remarkable sensitivity allowing detection of quantities of DNA as small as 2 fg (f = 10(-15) g) corresponding to less than 1/50th of the DNA contents in a single tachyzoite. The method is currently being applied using the in situ hybridization technique. One hundred samples (sera, CSF, broncho-alveolar washings, biopsies), mostly from immunocompromised patients, have been studied by the Southern-blot method. The results are still preliminary but appear very encouraging, especially since serological diagnostic studies during acquired or post-therapeutic immunodeficiencies (transplants) are usually impossible. Nevertheless, as it has already been reported in various other applications, the risk of false positive results requires that PCR be performed with highly rigorous technique, particularly in order to avoid any contamination by foreign DNA. An analysis of restriction profiles by the Southern method has also been carried out in 6 different strains of Toxoplasma gondii. Although a certain number of DNA fragments are common to all strains, some fractions of greater than 1.6 kb could characterize certain isolates. This protocol which is still preliminary is currently in progress and will be carried out in a larger number of cloned strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863858 TI - [From cholesterol to lipoprotein particle markers and/or risk factors]. AB - Among the risk factors for atherosclerosis, lipoproteins play a central role, particularly in the development of coronary artery disease. The plasma cholesterol level was the first definite indicator of the risk factor. Thereafter, technical progress has permitted the measurement of the cholesterol fractions, LDL cholesterol which is positively correlated with atherosclerosis, and HDL cholesterol, which is protective. However, the measurement of these fractions in a subject does not permit accurate determination of the risk to the subject. Likewise the measurement of apo A-I and B has brought an improvement in determining the risk factor but is still insufficient. The clarification of new markers would allow better definition of the potential atherogenic risk to a given individual Lp A-I (lipoproteins containing apo A-I but not apo A-II) level is probably an important indicator. Similarly, Lp(a) level is certainly an atherogenic lipoprotein and the apo E phenotype modulates the development of atherosclerosis. All these new markers and others, in the future, will better define the risk for an asymptomatic subject, with regard of atherosclerosis and therefore help to prevent it. PMID- 1863859 TI - [Drug therapy, testimony to our world and our time]. AB - The past decade has undoubtedly been that of the planetarization of society's problems. The medicament has not escaped this, being at the very heart of health politics, and it even provides us with significant proof of this phenomenon. AIDS, itself a planetary plague, has revealed in this area, the universal search for therapy. The development of methodological pharmaceutical research means that it is increasingly dependent on the general development of science and technology. The discovery process is becoming longer and more costly and its success is even more uncertain as the criteria of therapeutic innovation are increasingly severe, raising the problem of the adequacy for medical challenges and contemporary medical practices. The same questions are raised in the economic sector, from now on dominated by the insistence on rationalizing treatment costs. The idea of valuation applied to therapy forms an appealing but ambiguous approach which leads to the standardization of therapy protocols and pushes the debate even as far as freedom of prescription. This economic debate becomes particularly prickly when dealing with the problem posed by humanitarian issues in Third World Countries. The exclusion of a very big part of the world's population from access to quality medicines forces us to rethink medical cooperation as a whole. This should be founded on the mutual responsibility of those involved and no longer on a misguided idea of aid. The future of medicine in the world therefore depends on the identification and resolution of a certain number of contradictions. This is in everybody's interests and current experiences show that it is possible. PMID- 1863860 TI - [Address of Mr. Andre Delmas, retiring president. Evaluation of academic activities in 1990]. PMID- 1863861 TI - [Eulogy for Andre Hadengue (1913-1990)]. PMID- 1863862 TI - [Alpha-L-fucosidase of normal and pathological blood cells]. AB - The glycosidases, enzymes which participate in the degradation of glycoproteins and glycolipids inside the lysosomes are themselves glycoproteins and, for one enzyme, several forms may be isolated in tissues and in biological fluids, corresponding to variations in the composition or the structure of their glycanic moiety. We have previously studied the different forms of alpha-L-fucosidase in human serum, kidney and urine. Some modifications of the glycanic fraction of glycoproteins have been described in various forms of tumoral cells; therefore, we have attempted to verify if the alpha-L-fucosidase of blood cells might be a useful marker in the diagnosis of leukemias, using the enzymic pattern obtained by chromatographic or electrofocusing methods. Detergent extracts from normal lymphocytes, submitted to ion-exchange chromatography as well as to chromatofocusing, revealed the presence of two forms of alpha-L-fucosidase, A and B, with respective pIs of 5.7 and 6.2. After treatment by neuraminidase, these two forms remain distinct, showing that the degrees of sialylation is not the only difference. Moreover, after desialylation, the two forms have not the same affinity for concanavalin A, an argument for the heterogeneity of the glycanic structures. The determination of the total activity, and of enzymic patterns of alpha-L-fucosidase from leukemic cells led to the observation of three types of modifications, in comparison with normal lymphocytes: quantitative variations in the total activity; variations in the proportions of the two forms; variations due to the modification of pIs. We have studied the lymphocytes from four patients with a hairy-cell leukemia (HCL), four patients with chronic lymphoid leukemia (CLL) and the MO cell-line, proceeding from a HCL. In all cases, the total fucosidase activity is strongly decreased in comparison with normal lymphocytes activity. The chromatofocusing pattern for CLL cells reveals the presence of the A and B forms, without modification of their eluting pH. A characteristic pattern is obtained with hairy cells, presenting only the B form, eluted in more acidic conditions. The normal lymphocytes in peripheral blood are for 80 per cent of the T phenotype, and the CLL lymphocytes exhibit the phenotypic markers B, as well as the hairy cells, but the MO cell-line acquires in culture the T markers. As these last cells express both the A and B forms of enzyme, the absence of the A form of alpha-L-fucosidase seems to be a marker of the HCL.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1863863 TI - [Terminology. Report of activities for 1990 of the Terminology Group (Commission no. XIV--french)]. PMID- 1863864 TI - [Medicine and the European community on January 1st 1993]. AB - The European Community single act will come into effect on January 1st 1993 in the twelve countries belonging to the Community. It will have many outcomes in the health field. Some aspects concerning, in the name of the free circulation of goods and persons, are raised: certifications and training harmonization, drugs, food products, and all kinds of chemicals, regulations, standards for diagnosis and treatment equipment, blood products, methods of sampling, manufacturing and selling, etc. In the Community, priority is given to economic considerations, health problems are not much taken into account, administrative complexities will increase. So it is not sure that the Community will protect citizens' health better than the member States in their own countries. PMID- 1863865 TI - [Medical archives of former french overseas colonies put in storage in the Institute of Tropical Medicine in the Military Health Service]. AB - Presentation of medical archives of overseas territories stored at the Army Tropical Medicine Institute. They constitute a precious documentation from 1925 to 1961, concerning all the sides of the sanitary deed of France overseas. PMID- 1863866 TI - [Seroepidemiological data on anisakiasis: prophylactic consequences in fish products]. AB - The Western blotting method allowed us to confirm the diagnosis in 7 cases of acute anisakiasis, to assess it in 5 cases of chronic anisakiasis, and to follow up the evolution. These chronic frames according to the question of their long term evolution, and the part played by Anisakis simplex in fish nutritional allergy increase the negative score of that parasite. This situation should leave to discuss preventive rules. PMID- 1863867 TI - [A demand for authorization for the use of sorbic acid and its salts in acidified, refrigerated salads]. PMID- 1863868 TI - [On the selection of foreign candidates for a 3rd cycle diploma in medical or surgical specialties]. PMID- 1863869 TI - [Long term results of surgery of aortic aneurysms]. AB - During 10 years, between 01.01.80 and 01.12.89, 838 patients have been operated on consequently for a A.A.A. in the vascular surgery department of the Hospital Pitie-Salpetriere (Paris). Post-operative death was 7.3% (51 patients) among 692 operated on without emergency and 41.7% (60 patients) among 146 patients operated on emergency. The study was undertaken with the 727 surviving patients (86.8%) for the long term follow-up. Only 25 patients (3.4%) were lost out, so 702 patients (96.6%) had complete recalls even to their late death until the fourth trimester 1990. Total deaths, were 172 patients, (24.5%) out of the 702 patients in the follow-up. 60 patients (34.9%) died from cancer, 52 patients (30.2%) from heart disease, 21 patients (12.2%) from C.V.A. (cerebro-vascular-accident), 8 (4.6%) from rupture of aneurysm, 6 (3.6%) from renal insufficiency, 5 (2.9%) from prosthesis infection, 10 (5.8%) died from known reasons, 10 (5.8%) from unknown reasons. All these results were studied according to the "actuarial method" and the conclusions were as follow. The actual survival rate at 5 years was 72.1% +/- 5.6% and the average annual death rate was 5.8%. The factors which have influenced the late death are: a) Patients age: survival rate at 5 years and average annual death rate were significantly different whether the patients were less or more than 70 at the time of surgery. b) Surgical circonstances: late survival was significatively less with patients operated on emergency. c) Cerebro vascular insufficiency. The average annual rates from cardio-vascular and cerebro vascular accident were significatively more important in patients which previously had cerebro-vascular insufficiency. This work shows out that cardiac death are slightly overcame by cancer, but these two factors represent almost 2/3 (65.1%) of late death. So it should be important for prevention of late death to screen for lung and E.N.T. cancers. Some authors have proposed for prevention of coronarian accidents extensive use of coronarography and myocardial revascularisation. We prefer more acute screening than aggressive methods for patients with coronary problem who had surgery for A.A.A. and specially when they are less than 70 at surgical time. PMID- 1863870 TI - [Structural characteristics of the human lipoprotein lipase gene]. AB - Lipoprotein lipase plays a major role in the metabolism of circulating triglyceride-rich lipoproteins. In relation with this study, the fundamental results concerning the structure of human LPL gene are first summarized. Sequencing of this gene enabled us to characterize an Alu sequence. Interest of these repetitive sequences is exposed. PMID- 1863871 TI - Chemotherapy of metastatic Merkel cell cancer. AB - Out of 16 cases of Merkel cell cancer identified in the records of the Mt. Sinai Medical Center or affiliates, 11 patients developed systemic metastases. Literature review confirms the substantial possibility of dissemination. Both in our series and in the literature, cytotoxic chemotherapy produced a high rate of usually short-lived response, although one of our patients with disseminated metastases achieved complete remission for two years. PMID- 1863872 TI - Fungal infections in cancer patients. PMID- 1863873 TI - Natural killer cells: immunobiology and clinical prospects. PMID- 1863874 TI - Antisense agents in cancer research and therapeutics. PMID- 1863875 TI - Overview of monoclonal antibodies in the diagnosis and therapy of cancer. AB - Monoclonal antibodies initially offered the promise of a cure for cancer as "magic bullets" but this hope was quickly diminished as the complexities of the host-tumor relationship were realized. We have acquired a tremendous amount of practical experience since the first cancer patient was treated with a MAb nearly 10 years ago. This experience, combined with recent advances in recombinant DNA technology, has endowed us with a rich variety of opportunities to exploit in the diagnosis and treatment of malignancies. If recent preclinical research studies are clinically applicable and the antitumor responses seen in initial clinical trials can be optimized and confirmed, the next decade will likely be host to remarkable advances in the diagnosis and treatment of cancer with MAbs. PMID- 1863876 TI - Immunotoxins in the therapy of leukemias and lymphomas. PMID- 1863877 TI - Re: "Applications of immunocytochemistry to clinical cytology". PMID- 1863878 TI - Neuromuscular blocking agents and sedative drugs. Clinical uses and toxic effects in the critical care unit. AB - The use of sedatives and muscle relaxants is common in the ICU. Therapeutic goals should be carefully established. Monitoring of desired effects and toxic side effects is essential to avoid preventable morbidity. PMID- 1863879 TI - Toxic effects of drugs used in the ICU. PMID- 1863880 TI - Toxic effects of drugs used in the ICU. Antiarrhythmic agents. AB - Supraventricular and ventricular arrhythmias remain relatively commonplace in the ICU. Proper pharmacologic treatment requires that the clinician recognize accompanying disease states that may alter the pharmacokinetics and pharmacodynamics of antiarrhythmic drugs. In addition, knowledge of cardiovascular toxicity, noncardiovascular adverse effects, and drug-drug interactions are necessary to optimize antiarrhythmic drug therapy. PMID- 1863881 TI - Toxic effects of drugs used in the ICU. Anticonvulsant agents. AB - Anticonvulsant agents are often placed into two groups: those that complicate drug administration in a relatively predictable manner and those that cause idiosyncratic reactions that are relatively unpredictable, unheralded, and frequently quite severe. This article examines the toxic effects of anticonvulsant drugs used to treat diseases commonly seen in the intensive care unit (ICU), where the situation is complicated by the severity of the primary pathologic condition, which frequently involves the use of drugs that may have a significant effect on the blood levels and efficacy of the anticonvulsant drugs. Complications associated with the route of drug administration and their signs and symptoms are also discussed. PMID- 1863882 TI - Toxic effects of drugs used in the ICU. Anticoagulants and thrombolytics. Risks and benefits. AB - Anticoagulation is being used increasingly in the critical care areas. Thrombolytic therapy is now commonly used in emergency departments and coronary care units for treatment of AMI. Heparin therapy for unstable angina and for a 48 to 72 hour period following thrombolytic therapy for AMI is becoming commonplace. Beginning warfarin therapy concomitantly with heparin to decrease the total duration of heparin and the duration of hospital stay for DVT therapy is encouraged. The use of low-dose warfarin to prevent DVT in hip surgery, improve catheter patency, and prevent catheter-related subclavian thrombosis is increasing. Along with the increased use of anticoagulation must come a greater appreciation of the complications associated with the agents used, and of how to prevent or treat the hemorrhagic or thrombotic morbidity that may arise. Acute hemorrhage with thrombolytic agents must be recognized and the immediate implementation of conservative and aggressive measures begun. Heparin-induced thrombocytopenia with thrombosis is an often-unrecognized problem that may occur in 1% to 2% of heparin recipients and result in limb amputations. A delayed onset (6-10 days) requires frequent platelet counts for early diagnosis and treatment. The resurgence of warfarin use for prevention of cardiovascular and cerebrovascular disorders demands observation for skin necrosis from protein C and S inhibition. Early recognition of symptoms and syndromes associated with organ system hemorrhage in patients receiving chronic anticoagulation is imperative. The use of antagonists, such as protamine sulfate for heparin, vitamin K1 for warfarin, and antifibrinolytic drugs for thrombolytic agents, may be necessary in treating hemorrhagic events. However, their use may worsen the thromboembolic event initially treated. PMID- 1863883 TI - Inotropic agents. Catecholamines, digoxin, amrinone. AB - Three broad categories of pharmacologic support that enhance myocardial contractility and modify organ blood flow are reviewed. Appropriate selection among these compounds will minimize the occurrence of adverse effects. The catecholamines increase cardiac work and myocardial oxygen demand. In the setting of a failing ventricle, the increase in oxygen requirement may be balanced by improved coronary blood flow. Problems associated with catecholamines include tachycardia, induction of dysrhythmias, and unsuitable vasoconstriction. Epinephrine and isoproterenol are most likely to increase heart rate excessively. Norepinephrine is most likely to be associated with poor tissue perfusion. Amrinone, a bipyridine, has a favorable effect on oxygen balance in the failing ventricle and is unlikely to produce tachycardia or dysrhythmias. Principal concerns are the potential for accumulation in the patient with multiple organ system failure and the lack of pharmacokinetic information in critically ill patients, including children. Thrombocytopenia may be a problem as well. Digitalis glycosides are venerable drugs. Acute and chronic toxicity are problems that the intensivist is called on to treat frequently. Therapy with digitalis Fab fragments is now routine for severe intoxications and should improve outcome. PMID- 1863884 TI - Opioids and other analgesics. Adverse effects in the intensive care unit. AB - Analgesics are an important component of care for critically ill patients. The agents available--opioids, anesthetics, and NSAIDs--are efficacious, but each is capable of inducing a variety of adverse effects. Many adverse effects associated with opioid use can be minimized with the use of anticipatory measures. Anesthetic agents and NSAIDs offer less effect on cardiovascular and respiratory function than opioids, but are not without adverse effects. A thorough understanding of analgesic-associated adverse effects and drug interactions, as well as methods for anticipating and monitoring them, can help to minimize their effect on the ICU patient. PMID- 1863885 TI - Toxic effects of drugs used in the ICU. Toxic effects of bronchodilators. AB - The critical care clinician commonly encounters patients with acute bronchospasm. Therapy includes a multidrug regimen of sympathomimetics, anticholinergics, methylxanthines, and corticosteroids. The best use of these agents is predicated on knowledge and avoidance of drug toxicities. This article reviews toxic effects of these bronchodilator agents. PMID- 1863886 TI - Toxic effects of electrolyte and trace mineral administration in the intensive care unit. AB - Electrolytes and trace minerals are administered routinely to ICU patients to correct deficiencies or as specific therapy for various conditions. Complications are usually related to the rate of infusion, rapidity of correction of a deficiency state, or iatrogenic poisoning with the agent. Adverse effects associated with Na+ administration included volume overload, CPM, and central nervous system bleeds. The toxic effects of K+, Ca2+, and Mg2+ are primarily related to their effects on the myocardium, nervous system, and muscle. Other than precipitating or maintaining a metabolic acidosis, Cl- administration is relatively nontoxic. Its accompanying anion (i.e., ammonium or arginine), however, may contribute significantly to patient morbidity and, possibly, mortality. Side effects observed with phosphate administration include hypocalcemia, metastatic calcification, and hypernatremia or hyperkalemia. Most of these toxicities are avoidable if appropriate precautions are taken and appropriate monitoring implemented. Finally, when administering any of these agents, the intensivist should be familiar with their toxicologic profiles and management of potential complications. PMID- 1863887 TI - Steroids and biologic agents in the intensive care unit. AB - We have reviewed the actions, indications, and toxicity of steroids and several important biologic pharmaceutical agents used in critical care medicine. This is a rapidly expanding area of therapeutics. Space limitations prevent an exhaustive review of all biologic pharmaceuticals, such as tissue plasminogen activating substance, hormones (e.g., thyroid, insulin, growth hormone, erythropoietin), clotting factors, and blood products. The future of biologic pharmaceuticals appears to be bright in the face of new biotechnology, and the critical care physician can anticipate new and exciting treatments to evolve from current basic and clinical research into biologic agents. PMID- 1863888 TI - Grass under scrutiny. PMID- 1863889 TI - Inhaled drugs and the lung. PMID- 1863890 TI - Emergency treatment of allergic reactions to Hymenoptera stings. AB - Allergic reactions to Hymenoptera stings are frequently observed all over Europe. Rarely they may induce long-standing morbidity or even be fatal. Several investigations have shown that the emergency treatment given to these patients is often inadequate. Cutaneous symptoms respond well to antihistamines and also to adrenaline. Adrenaline is the mainstay for outside hospital treatment of more severe reactions involving the respiratory tract (bronchial asthma, laryngeal oedema) and the cardiovascular system (anaphylactic shock). Inhaled adrenaline is especially useful in respiratory symptoms, while parenteral application of adrenaline is prefered for shock treatment. All patients with severe respiratory or cardiovascular reactions must be hospitalized, treated under intensive care conditions and observed for at least 24 hr. Emergency medications including adrenaline for inhalation or for self-injection must be given to all patients with a history of systemic allergic reactions to hymenoptera stings. These patients must also get instructions for safety measures to avoid further stings. They should be referred to an allergist in order to evaluate the indication for venom immunotherapy. PMID- 1863891 TI - The role of IgG subclass antibodies in the clinical response to immunotherapy in allergic disease. PMID- 1863892 TI - Group V allergens in grass pollens. I. Purification and characterization of the group V allergen from Phleum pratense pollen, Phl p V. AB - An allergen from Phleum pratense (timothy) pollen, Phl p V, has been isolated by a combination of copper chelate affinity chromatography and ion exchange chromatography. Phl p V binds IgE from serum of grass-sensitized donors as revealed in immunoelectrophoretic techniques and in SDS-PAGE immunoblot, and luminescence immunoassay (LIA) inhibition experiments indicate that the allergen represents a significant part of the IgE binding capacity of the extract. In immunoelectrophoresis, Phl p V is revealed as a single precipitate. However, molecular weight studies show that Phl p V consists of at least two isoforms with similar immunochemical properties, but with different molecular size. After SDS PAGE treatment purified Phl p V is identified as two IgE-binding components, Phl p Va and Phl p Vb, with molecular weights 33 and 29 kD. After HPLC gel filtration, Phl p Va and Phl p Vb are identified in the major 30-kD eluate. After Sephadex G75 gel filtration of whole pollen extract, Phl p V is identified in fractions corresponding to molecular weights 47 and 25 kD. The 47-kD fraction corresponds to Phl p Va/Phl p Vb as seen in SDS-PAGE, while the 25-kD component presumably corresponds to a degradation product present in whole pollen extract. The NH2-terminal sequence of Phl p V, corresponding to approximately 10% of the molecule, has been determined. The sequence shows minor variations in some residues and contains besides many alanine residues also hydroxyproline; the sequence reveals no homologies to any known NH2 terminal sequence of other proteins. The amino acid composition, revealing 26 mole % alanine and no cysteine, does not show any similarities to other known amino acid compositions of allergens. From the amino acid composition determination and an immunoelectrophoretic comparison, Phl p V is estimated to represent 6% (w/w) of the whole pollen extract. PMID- 1863893 TI - Group V allergens in grass pollens. II. Investigation of group V allergens in pollens from 10 grasses. AB - In an earlier study an allergen from Phleum pratense (timothy) pollen, Phl p V, has been isolated and physicochemically characterized. In this study Phl p V and immunochemically similar components from other grass pollens (group V allergens) have been investigated using immunoelectrophoretic techniques. To study the allergenic importance of the group V allergens, the allergenic compositions of 10 grass pollen extracts were investigated in crossed radioimmunoelectrophoresis (CRIE) using 20 sera from grass pollen-allergic donors. Group V allergens were identified using monospecific rabbit antibodies raised against Phl p V, anti-Phl p V, which react with other group V allergens usually producing dense precipitates in immunoelectrophoresis. In this way group V allergens were identified in eight extracts, and when present the precipitate corresponding to the group V allergen was the dominant IgE binding precipitate. All identified group V allergens bound IgE in at least 17 of the 20 investigated sera. Monospecific rabbit antibodies raised against the group I allergen of Lolium perenne (rye grass), anti-Lol p I, do not precipitate group V allergens, indicating that there are no immunochemical similarities between group I and group V allergens. In SDS-PAGE anti-Phl p V identifies IgE-binding components with molecular weights between 26 and 33 kD. In contrast, anti-Lol p I binds to components of slightly higher molecular weight. Apparently, the group V components are allergens that are physicochemically and immunochemically distinct from group I allergens. PMID- 1863894 TI - Purification and characterization of the major dog allergen, Can f I. AB - An important dog-hair and dander-specific allergen Ag13 has been purified by means of immunoaffinity chromatography utilizing rabbit antibody specific for Ag13. Purity was judged to be very high as detected by crossed immunoelectrophoresis and SDS-PAGE. The purified allergen was subjected to amino acid analyses. Molecular weight was about 22 kD in HPLC-gel filtration and 25 kD in SDS-PAGE with an additional band at 18 kD. In vitro IgE binding of the allergen was investigated by luminescence immunoassay (LIA) inhibition. Removal of Ag13 from dog hair and dander extract (DHD) removed 50 +/- 1.5% of the IgE binding capacity. The purified allergen inhibited up to 56.5% of the IgE activity to DHD as measured with a pool of serum from dog-allergic patients. Out of 26 dog allergic patients, 24 had a positive skin-prick test to the allergen. Out of 23 dog-allergic patients, 16 reacted with the allergen in IgE immunoblotting. We suggest that Ag13 be termed Can f I. The allergen will be a marker allergen for environmental dog hair and dander exposure. PMID- 1863895 TI - Olive pollen induces asthmatic response. AB - We provide evidence that olive pollen extract can induce asthmatic response. The pattern of airway response to olive pollen is investigated. Nineteen patients with seasonal allergic rhinitis and asthma, suspected to be due to olive pollen, all of whom had positive skin-prick test, were investigated. Bronchial challenge with olive pollen extract were performed and the peak flow rate was followed for 20 hr. Eight patients developed dual asthmatic response (DAR), six patients developed early asthmatic response (EAR) and five patients had no asthmatic response. The early maximal fall in FEV1 and the PD15 were not different between the group with DAR and the group with EAR only. We conclude that olive pollen can induce dual asthmatic response. PMID- 1863896 TI - Dermal blood flow after local challenges with allergen, histamine, bradykinin and compound 48/80. AB - Blood flow was determined in weal and flare reactions and in late dermal reactions after skin-prick tests with allergen, histamine, bradykinin and compound 48/80 in pollen-allergic subjects. Local blood flow was measured with laser Doppler flowmetry intermittently for up to 48 hr at three distances from the prick centre (2 mm; weal, 15 mm; flare and 30 mm). Continuous recordings were also made in the weal area after challenge with bradykinn and compound 48/80. The size of the induced weal and flare area of all the substances and the late phase after allergen was determined using digitized planimetry. Furthermore, simultaneous determinations of local dermal temperature and blood flow in the weal and flare site were performed intermittently for 6 hr after allergen and histamine challenges. There was a dose-dependent and distance-related increase in blood flow for all the substances tested. The blood flow in the 2-mm registrations had normalized 20 min after bradykinin, 1.5-2 hr after histamine and 3 hr after compound 48/80, while allergen induced a continuous increase in blood flow for more than 24 hr. The area of the weal and flare reaction was dose related for all substances, and a similar dose-dependent increase was noted for the observed dermal late-phase reactions present after allergen. The local temperature after challenge with allergen and histamine was also increased in a distance-dependent manner. These studies suggest that laser Doppler flowmetry is a sensitive and reproducible method to quantify blood flow changes occurring after skin-prick tests. Different putative mediators or mast cell stimulating substances produce various response profiles, all of which differ from those observed after allergen. Temperature measurements after skin-prick tests seem to follow the observed changes in blood flow as measured with laser Doppler flowmetry, which may be why both techniques might reflect changes in capillary blood flow. PMID- 1863897 TI - Childhood asthma: clinical and immunological changes over a decade. AB - A group of 26 Australian asthmatic children with laboratory-proven bronchial hyper-reactivity to the allergens of rye grass pollen and/or the house dust mite has been studied over a 9-year period. Clinical symptoms and drug scores were used to evaluate the severity of the patients' asthma and, wherever possible, blood samples were obtained before, during and after the rye grass pollen seasons. The cumulative symptom and drug scores for the 20 patients with bronchial hyper-reactivity to rye grass pollen extract tended to increase during and fall after each pollen season but the peaks were of decreasing amplitude over the 9 years. Since a proportion of these patients underwent hyposensitization to rye grass during year 1, longitudinal comparisons were made between year 2 and year 9. Comparing the individuals at the same three seasonal time-points revealed significantly lower drug scores in year 9 compared with year 2, and in parallel with this, significantly lower total IgE, IgE anti-rye and IgG anti-rye antibodies at all three assessment points. In the 14 patients with bronchial hyper-reactivity to house dust mite the severity of the asthma and the median levels of IgE and IgG mite specific antibodies all decreased over the study period. Despite the progressive improvement in asthma and diminishing immune responses to both rye grass and house mite in the patients, no immunological feature could be identified that correlated significantly with clinical outcome. PMID- 1863898 TI - House dust mite allergens on different types of mattresses. AB - Beds and especially mattresses are important breeding grounds for house dust mites. We investigated whether supposed differences in the microclimate on water, spring and foam mattresses were reflected in the occurrence of house dust mite major allergens (Der fI, Der mI, and Der pI) in mattress dust. Fifty-one mattresses that had been in use for 8-25 months were sampled. Median concentration of total major allergens was 0.5 microgram/g dust (range 0-45) with little difference between the three major allergens and between the three types of mattresses. Occurrence of mattresses with concentrations above and below the proposed risk level (2 micrograms/g) was similar in the mattress groups. However, the allergen concentration was above risk level in 56%, if washable underblankets were not applied, compared with only 21% in the group with such underblankets. In conclusion, mattresses tend to accumulate allergen rather rapidly. Neither heated water mattresses, spring nor foam mattresses seem to be of any advantage for mite allergics, whereas underblankets made of synthetic fibres in a cotton or synthetic cover, commonly used in Denmark, might play a beneficial role in reducing allergen exposure. PMID- 1863899 TI - The significance of specific IgG and IgG4 antibodies to a reactive dye in exposed workers. AB - To evaluate the significance of specific IgG and specific IgG4 in the development of work-related respiratory symptoms, specific IgG and specific IgG4 to Black GR human serum albumin (HSA) conjugate were measured by ELISA in 309 dye-exposed workers and 63 unexposed patients as negative controls. A survey revealed that 78 (25.2%) had work-related lower respiratory symptoms with or without nasal, skin or eye symptoms. Specific IgG and specific IgG4 were detected in 23% and 14% of the exposed workers, respectively. The prevalence of specific IgG and specific IgG4 was significantly higher in smokers and workers with specific IgE or those with lower respiratory symptoms (P less than 0.05), but was not associated with work station, duration of dye exposure or atopy. These results suggested that the existence of specific IgG to Black GR-HSA might represent a response to Black GR exposure and be closely related with work-related respiratory symptoms. PMID- 1863900 TI - Changes in the levels of house dust mite specific IgG4 during immunotherapy in asthmatic children. AB - Serum levels of IgG subclass and house dust mite (Dermatophagoides pteronyssinus, Dpt) specific IgG4 were evaluated during immunotherapy in asthmatic children. Asthmatic children undergoing long-term immunotherapy (more than 2 years) posed a mean value of total serum IgG4 or Dpt-specific IgG4 antibodies significantly higher than that of patients prior to receiving immunotherapy, asthmatic (placebo) controls, or patients undergoing short-term immunotherapy (less than 1 year) (P less than 0.05). The mean levels of serum Dpt-specific IgG4 in all asthmatic groups were also significantly higher than in the non-allergic controls (P less than 0.01). Moreover, the mean level of Dpt-specific IgG4 tended to increase during immunotherapy. A significant correlation between total serum IgG4 and Dpt-specific IgG4 antibodies was noted (r = 0.6243; P less than 0.001). Serial follow-up reveals that Dpt-specific IgG4 levels usually rose significantly with clinical improvement in asthmatic children during immunotherapy. These results suggest that the anti-mite-specific IgG4 antibody may serve as an indicator for clinical outcome of mite allergy during immunotherapy. PMID- 1863902 TI - Eosinophils in late cutaneous reactions. PMID- 1863901 TI - Clinical and immunological characteristics of Brazil nut allergy. AB - Twelve cases of allergy to Brazil nut have been recorded in the last 8 years. The reaction is usually IgE mediated and most patients have other atopic diseases. There appear to be several proteins with potent antigenic components in Brazil nut. PMID- 1863903 TI - Therapy of bronchial hyper-responsiveness. PMID- 1863904 TI - The 1990 Pharmaceutical Manufacturers Association of Canada keynote lecture. The role of the cytochromes P450 in the detoxication and activation of drugs and other chemicals. AB - The roles of the cytochromes P450 are reviewed, with emphasis on their involvement in the detoxication of drugs and chemicals, the activation of carcinogens, and the toxicity of drugs. Cytochromes P450 have different characteristics. P450I mostly activates carcinogens and other chemicals by forming oxygenated reactive intermediates, which are also associated with the formation of neoantigens and immunotoxicity. P450IIE has a propensity to form oxygen radicals, which are cytotoxic and carcinogenic; other cytochromes generate oxygen radicals by futile cycling when activated by difficulty metabolized substrates. Novel procedures for the safety evaluation of chemicals are described; COMPACT is based on the computer graphic determination of the spatial conformation and electronic structure of chemicals to enable their activating cytochromes P450, and hence their toxicity, to be established; ENACT is based on quantifying the induction of individual cytochromes P450, since the extent of induction of P450I, and possibly other activating cytochromes, is directly related to the carcinogenic potential of the chemical. PMID- 1863905 TI - Effects of ethanol exposure on the embryo-fetus: experimental considerations, mechanisms, and the role of prostaglandins. AB - The purpose of this review is to critically examine the effects of ethanol on the embryo-fetus. There has been a tremendous amount of human epidemiological and experimental animal research on the characterization of the anomalies produced by chronic prenatal ethanol exposure and the identification of critical periods of vulnerability and critical amounts of ethanol necessary to produce fetal effects and (or) abnormal development. Few studies have examined the underlying mechanism(s) of the action of ethanol, and even fewer studies have examined the effects of single-dose ethanol exposure on the embryo-fetus. In this review, the current state of knowledge of the effects of chronic use of ethanol on the embryo fetus is summarized. The primary focus of the review is on the embryonic-fetal effects of acute ethanol exposure, with particular emphasis on the ethanol induced suppression of fetal breathing movements, as this effect appears to be a very sensitive index of acute exposure of the near-term fetus to ethanol. Factors to be considered in the selection of experimental animals to investigate the mechanism of action of ethanol and to study the acute effects of ethanol are discussed. Postulated mechanisms of action of ethanol on the embryo-fetus are evaluated with a focus on the role of prostaglandins. Finally, future directions in this field of research are proposed. PMID- 1863906 TI - Quantitative proton nuclear magnetic resonance of plasma for screening hepatic metabolism during ethanol infusion in cats. AB - The effects of increasing blood ethanol levels on hepatic metabolism were studied in anesthetized cats whose prior fluid intake contained ethanol for 24 days. A hepatic venous long-circuit technique with an extracorporeal reservoir was used to allow hemodynamic measurements and repeated sampling of arterial, portal, and hepatic venous blood without depletion of blood volume. For ethanol, Vmax was 106 +/- 15 mumol.min-1.100 g-1 liver and Km was 164 +/- 31 microM. A previous study showed that there were no changes in O2 uptake by the liver, suggesting other oxidative processes were suppressed during ethanol metabolism. In this study, proton nuclear magnetic resonance spectroscopy was used to simultaneously screen several plasma metabolites to elucidate other metabolic processes that may be perturbed in the liver during ethanol infusion. Hepatic lactate uptake remained unaltered when ethanol metabolism was less than 0.5 Vmax but was suppressed on an equimolar basis with ethanol metabolism when ethanol metabolism rose above 0.5 Vmax. Thus, lactate oxidation is one process that can be suppressed to allow ethanol oxidation without additional O2 uptake by the liver. In addition, no release of acetate from the liver occurred during ethanol metabolism in these experiments. This surprising finding suggests ethanol metabolism may, under some conditions or in some species, result in fatty acid synthesis rather than acetate release. Eight other major metabolites remained unchanged during ethanol infusion. PMID- 1863907 TI - Plasma glutathione turnover in the rat: effect of fasting and buthionine sulfoximine. AB - Hepatic glutathione (GSH) plays an important role in the detoxification of reactive molecular intermediates. Because of evidence that the intrahepatic turnover of glutathione in the rat may be largely accounted for by efflux from hepatocytes into the general circulation, the quantitation of plasma GSH turnover in vivo could provide a noninvasive index of hepatic glutathione metabolism. We developed a method to estimate plasma glutathione turnover and clearance in the intact, anesthetized rat using a 30-min unprimed, continuous infusion of 35S labelled GSH. A steady state of free plasma glutathione specific radioactivity was achieved within 10 min, as determined by high-pressure liquid chromatography with fluorometric detection after precolumn derivatization of the plasma samples with monobromobimane. The method was tested after two treatments known to alter hepatic GSH metabolism: 90 min after intraperitoneal injection of 4 mmol/kg buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, and after a 48-h fast. Liver glutathione concentration (mean +/- SEM) was 5.00 +/- 0.53 mumol/g wet weight in control rats. It decreased to 3.10 +/- 0.35 mumol/g wet weight after BSO injection and to 3.36 +/- 0.14 mumol/g wet weight after fasting (both p less than 0.05). Plasma glutathione turnover was 63.0 +/- 7.46 nmol.min 1.100 g-1 body weight in control rats, 35.0 +/- 2.92 nmol.min-1.g-1 body weight in BSO-treated rats, and 41.7 +/- 2.28 nmol.min-1.g-1 body weight after fasting (both p less than 0.05), thus reflecting the hepatic alterations. This approach might prove useful in the noninvasive assessment of liver glutathione status. PMID- 1863908 TI - Evidence for bumetanide-sensitive, Na(+)-dependent, partial Na-K-Cl co-transport in red blood cells of a primitive fish. AB - Tracer uptake studies identified the major routes for K+ transport in hagfish red cells, resolving them into ouabain-sensitive, loop diuretic-sensitive, and residual components. The K1/2 values for ouabain, bumetanide, and furosemide were 10(-5), 6 x 10(-7), and 5 x 10(-6) M, respectively. The properties of the Na-K-Cl co-transporter were investigated further by varying K+, Na+, and Cl- concentrations. The measured K1/2 values were similar to those for human red cells. Finally, the stoichiometry of Na:K:Cl uptake was determined, giving 1:1 for K+:Cl-; in contrast, no significant Na+ flux could be measured, although Na+ content must be present for measurable bumetanide-dependent K+ or Cl- flux to occur. The Na-K-Cl transport therefore shows Na(+)-dependent KCl co-transport or partial flux of the system. PMID- 1863909 TI - Feeding diets containing 2% cheno- or urso-deoxycholic acid or cholestyramine to rats for two weeks alters intestinal morphology and bile acid absorption. AB - This study was undertaken to examine the effect of supplementing chow for 2 weeks with 2% cheno- (CDC) or ursodeoxycholic (UDC) acid or cholestyramine (CHOL) on the intestinal morphology and in vitro uptake of bile acids in adult rats. Food intake was higher in UDC and CHOL as compared with animals fed chow or CDC, or in animals pair-fed a chow-restricted diet (CRD). Body weight gain was lower in CDC and CRD but was unchanged by feeding UDC or CHOL. Jejunal mucosal surface area was similar in the five groups, although the ileal mucosal surface area was lower in UDC than in the other animals. Feeding UDC reduced the ileal uptake of cholic acid (C), taurocholic acid (TC), and glycocholic acid (GC). Feeding CDC had no effect on bile acid uptake except when compared with animals fed a chow restricted diet. Feeding CHOL reduced the active ileal uptake of C, had no effect on the uptake of TC or GC or CDC, and was associated with increased uptake of stearic, linoleic, and linolenic acids. These effects were likely related to a direct effect of changes in the luminal bile acids rather than due to an indirect effect of the reduced food intake, since the ileal uptake of CDC and GC was greater in animals fed CDC than in those fed a chow-restricted diet with comparable weight gain. Thus, 2 weeks of feeding bile acids or bile acid binding agents may alter the form and function of the rat intestine, and as well may lead to changes in food intake and body weight gain. PMID- 1863910 TI - Basic mechanisms of pain associated with deep tissues. AB - There are important differences in pain arising from deep tissues in comparison to cutaneous pain. These differences can be partially explained by the unique organization of nociceptive systems activated by stimulation of muscle, joint, or viscera. Recent evidence also indicates that stimulation of deep tissues can produce long-lasting changes in central nervous system excitability and, therefore, may play a prominent role in persistent or chronic pain conditions. These findings have important implications for the treatment of chronic deep tissue pain conditions. PMID- 1863911 TI - Considerations concerning the neurobiological basis of muscle pain. AB - Nociceptors in skeletal muscle can be sensitized by substances that are released from pathologically altered tissue. In the sensitized state, nociceptors can be activated by low-intensity stimulation; this is probably one of the mechanisms producing deep tenderness. Dorsal horn cells processing input from muscle nociceptors often have multiple receptive fields and additional input from other deep tissues or skin. This may be one of the reasons for the diffuse and ill localized nature of muscle pain. The degree of convergence from deep tissues and skin in neurones with muscle input can be increased by noxious stimulation of deep tissues. This mechanism might explain phenomena such as spread and referral of muscle pain. In the development of chronic muscle pain, vicious circles may be involved which operate locally in the damaged tissue or via spinal reflexes that alter the biochemical environment of the nociceptors in skeletal muscle. PMID- 1863912 TI - Mechanisms of pain arising from articular tissues. AB - This paper reviews the peripheral and central neural mechanisms underlying pain from articular tissues innervated by spinal and trigeminal afferents. The paper especially addresses trigeminal mechanisms related to pain from the temporomandibular joint and its associated craniofacial musculature. Recent studies have shown the existence of articular nociceptive primary afferents that project to the spinal cord dorsal horn and trigeminal brainstem complex. A particular feature of most neurones receiving these deep nociceptive afferent inputs is their responsivity also to cutaneous nociceptive afferent inputs. This suggests the involvement of these neurones not only in the detection of acute articular pain, but also in the hyperalgesia and poor localization, spread, and referral of pain that characterize many painful conditions of joints and other deep structures. While only limited information is available on related higher brain centre mechanisms, convergence and interaction between cutaneous and deep afferent inputs also seem to be a characteristic of somatosensory neurones in the thalamus and somatosensory cerebral cortex. Muscle and autonomic reflexes may be induced by such deep noxious stimuli, but the functional significance of some of these effects (e.g., in relation to clinical concepts of myofascial dysfunction) requires further study in more appropriate functional settings. PMID- 1863913 TI - Central mechanisms of visceral pain. AB - Deep pain arising from muscle, joints, connective tissue, and the viscera is different in character and quality from pain arising from cutaneous structures. Deep pains, particularly visceral pain, are poorly localized, typically referred or transferred to a cutaneous site, and generally produce strong emotional and autonomic responses and tonic muscle contractions. Despite the prevalence and clinical importance of deep pains, it is only relatively recently that investigative efforts have begun to focus on the mechanisms of deep pain. The present report briefly reviews the development and use of a model of visceral pain that employs constant pressure distension of the colon and rectum as a noxious stimulus. Converging behavioral, pharmacological, and physiological evidence that colorectal distension is a valid, reliable, noxious, visceral stimulus is presented. PMID- 1863914 TI - Arthritis and headache. AB - Pain researchers are committed to designing new experimental models as close as possible to the physiopathological conditions encountered in humans, with due concern for ethical considerations. Some current questions related to inflammation and headache are discussed, along with the approaches used to address them. These approaches are essential for a better understanding of the physiology, pharmacology, and treatment of various pain syndromes. PMID- 1863915 TI - The contribution of the nervous system to inflammation and inflammatory disease. AB - Recent studies have identified a major contribution of the nervous system to inflammation and to inflammatory disease. In particular, substances released from the peripheral terminals of small diameter primary afferent fibers and from sympathetic postganglionic nerve (SPGN) terminals have been implicated in several of the major components of acute inflammation (e.g., vasodilatation and plasma extravasation) as well as in the regulation of tissue injury in an inflammatory disease model, experimental arthritis in the rat. Although the release of peptides from primary afferent terminals has received the most attention, our studies have established an important contribution of mast cells and the SPGN terminals to acute inflammation. We describe studies which indicate that plasma extravasation provoked by activation of small diameter primary afferents in the knee joint of the rat involves a cascade of events in which the mast cell and then the sympathetic terminal are sequentially activated. Our studies indicate that release of prostaglandins, but neither norepinephrine nor neuropeptide Y, from the SPGN terminal contributes to increased plasma extravasation. Although activation of the SPGN terminal (via the mast cell) or more directly, via injection of bradykinin, increased plasma extravasation, surgical or pharmacological sympathectomy decreased the severity of experimental arthritis. In related studies we demonstrated that adrenal medullary-derived epinephrine can exacerbate arthritis through a beta-receptor-mediated regulation of the release of an as yet unidentified substance(s) from the SPGN terminal. Our results raise important questions as to whether acute inflammation contributes to tissue repair or to further injury in the setting of disease. PMID- 1863916 TI - Central mechanisms of vascular headaches. AB - The intracranial blood vessels supplying the dura and brain are innervated by sensory afferents from the trigeminal nerve. These fibers are believed to be responsible for conveying the pain associated with vascular head pain such as migraines. This paper reviews recently published data describing the existence of neurons within the cat trigeminal nucleus and thalamus that respond to electrical stimulation of the middle meningeal artery and superior sagittal sinus. Almost all of these neurons receive convergent input from the facial skin and most of the receptive fields include the periorbital region. On the basis of their cutaneous inputs, most of the neurons are classified as nociceptive. The characteristics of these cerebrovascular-activated neurons are consistent with their role in mediating vascular head pains and with the typical referral of such pains in man to the orbital region. This paper also presents preliminary results of recordings from rat trigeminal ganglion neurons activated by electrical stimulation of the middle meningeal artery and sagittal sinus. The latencies of activation of these neurons are indicative of conduction in slowly conducting myelinated axons and in unmyelinated axons. Some of the neurons could also be activated by mechanical stimuli applied to the vessels. PMID- 1863917 TI - Chronic muscle pain syndromes: an overview. PMID- 1863918 TI - Illness behavior and dysfunction: review of concepts and application to chronic pain. AB - The purpose of this presentation is to review the elements that comprise the concept of illness behavior including elaboration of a more formal theoretical and operational model for illness behavior and then discuss the application of the illness behavior model to chronic pain, especially chronic orofacial pain. The model of illness behavior presented emphasizes four critical areas of conceptual interest, namely, (1) monitoring of somatic signals; (2) cognitive processes whereby bodily symptoms are interpreted; (3) attaching meaning to symptoms in the context of emotional state and concurrent environmental events; and (4) the ethnocultural influences that pervade meaning and shape coping responses. Our model of illness behavior was generalized from a closely related model developed to guide research when the specific illness behavior of interest was dysfunctional chronic pain behavior. We also include a time dimension in our chronic pain model. Dysfunctional chronic pain is understood to be the most important undesirable consequence associated with suffering a persistent pain condition. Dysfunctional chronic pain is a subset of illness behaviors inconsistent with medically documented findings, while the complaints of pain are prominent. Changes occur in emotional status, most typically reported as mood and behavioral changes associated with depression, such as demoralization, helplessness, and social isolation. Excesses in medical care, hospitalizations for surgery, and abuse of medications are further characteristics of dysfunctional chronic pain. PMID- 1863919 TI - Fibromyalgia--a clinical entity? AB - Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain and tenderness at specified sites, fatigue, and unrefreshing sleep. The American College of Rheumatology (ACR) has recently accepted diagnostic criteria for FM. The ACR criteria have high diagnostic specificity, sensitivity, and accuracy. Laboratory investigations show a disturbed microcirculation in painful muscles, a decrease in adenosine triphosphate and phosphocreatine, and a reduced relaxation rate. Pain analyses indicate that the pain is nociceptive. A characteristic physiological sleep disturbance has been described that is correlated to the symptoms. The etiology of FM is not known. The etiology may be different in different patients. FM is a clinical entity, but should be regarded as a syndrome rather than a disease. PMID- 1863920 TI - Muscle pain, dyskinesia, and sleep. AB - Muscle pain and poor sleep commonly occur together. Whether pain induces poor sleep or vice versa is difficult to know. Muscle pain is also observed in the presence of some types of dyskinesia or movement disorders. The interaction between sleep, movement disorders, and some musculoskeletal pain appears to be complex and may be influenced by various concomitant psychological and (or) biological factors. PMID- 1863921 TI - The pain-adaptation model: a discussion of the relationship between chronic musculoskeletal pain and motor activity. AB - Articles describing motor function in five chronic musculoskeletal pain conditions (temporomandibular disorders, muscle tension headache, fibromyalgia, chronic lower back pain, and postexercise muscle soreness) were reviewed. It was concluded that the data do not support the commonly held view that the pain of these conditions is maintained by some form of tonic muscular hyperactivity. Instead, it seems clear that in these conditions the activity of agonist muscles is often reduced by pain, even when this does not arise from the muscle itself. On the other hand, pain causes small increases in the level of activity of the antagonist. As a consequence of these changes, force production and the range and velocity of movement of the affected body part are often reduced. To explain how such changes in the behaviour come about, we propose a neurophysiological model based on the phasic modulation of excitatory and inhibitory interneurons supplied by high-threshold sensory afferents. We suggest that the "dysfunction" that is characteristic of several types of chronic musculoskeletal pain is a normal protective adaptation and is not a cause of pain. PMID- 1863922 TI - Sensory and pharmacological modulation of pain. AB - Traditional neurosurgical methods to control pain have been replaced by a variety of modulation techniques. The major types of modulation are pharmacological, physical, and psychological. Important advances are occurring in the development of all three modulation approaches. PMID- 1863923 TI - Electrical stimulation of peripheral and central pathways for the relief of musculoskeletal pain. AB - One method for the treatment of chronic musculoskeletal pain involves stimulation of the peripheral or central nervous system. Such stimulation includes transcutaneous electrical nerve stimulation, dorsal column stimulation, and deep brain stimulation. This review discusses the clinical use of electrical stimulation for the relief of musculoskeletal pain, and describes the results of studies conducted in our laboratory suggesting that such stimulation reduces pain transmission along sensory-discriminative pathways. PMID- 1863924 TI - Can the use of physical modalities for pain control be rationalized by the research evidence? AB - Physical modalities, including cold and heat, are widely used in the conservative management of pain associated with musculoskeletal disorders. This review has critically appraised the literature supporting the use of these modalities in the treatment of musculoskeletal pain. It was concluded that, apart from a few exceptions and in a few types of disorders, existing evidence does not support the use of these modalities in long-term pain control. There was, however, evidence that several modalities, specifically cold and a form of deep heat (shortwave diathermy), do have short-lived analgesic effects and so may contribute to more painfree function in the short term. Further research is clearly warranted to define the short- and long-term therapeutic efficacy of physical modalities in the treatment of musculoskeletal pain to justify their continued use in clinical practice. PMID- 1863925 TI - The pharmacological control of musculoskeletal pain. AB - The modern therapy of the pain of inflammatory rheumatic disease and osteoarthritis is based on several advances in molecular biology, which are reviewed in this paper. Inhibition of the ubiquitous enzyme cyclooxygenase by the nonsteroidal anti-inflammatory drugs including the salicylates prevents the production of endoperoxides, which are pro-inflammatory, and prostaglandins E2 and I2, which sensitize peripheral pain receptors. In addition, a fundamental understanding of neural tracts that inhibit the pain signal has introduced the concept of giving low dose tricyclic antidepressants for chronic pain to block the re-uptake of serotonin from the neural cleft of synapses. This amplifies the effect of serotonin and catecholamines, which are neurotransmitters for these inhibitory tracts. PMID- 1863926 TI - Familial intracranial arachnoid cysts. AB - Three siblings with intracranial arachnoid cysts are described, two males and one female. One of the males has symmetric, bilateral, temporoparietal convexity cysts, and the others have singular, unilateral cysts. Three additional siblings in the family and other known relatives are clinically unaffected. As far as we know, this is the second reported case of familial intracranial arachnoid cysts and the first involving three siblings. The significance of these cysts and a review of the literature are presented. PMID- 1863927 TI - Occipital depression fractures in childhood. A report of 14 cases. AB - In this paper, we present 14 cases with depression fracture of the occipital bone in pediatric age. There were 7 males and 7 females. Their ages ranged from 1 year to 15 years with a median of 5.8 years. The most common causes were: falling (8 cases); traffic accidents (2); assault (2 cases). Five of our 14 cases had compound fractures and the remaining 9 had closed fractures. Epidural and subdural hematomas were observed in 5 and 1 cases, respectively. There was significant improvement in 11 cases; two patients died. PMID- 1863928 TI - Functional enuresis: pharmacological versus behavioral treatment. AB - Treatment of childhood enuresis requires a careful anamnesis, physical examination, urinalysis, and urine culture to determine if a subject is affected with functional or organic enuresis. Functional enuresis (FE) was present in the majority of our patients (168/204). These 168 subjects, aged from 6 to 11 years, were randomly divided into three therapy groups (pharmacological therapy, behavioral therapy, and behavioral therapy with the aid of a personal computer). Our study shows that behavioral therapy gave better results in FE than did pharmacological therapy. We point out the usefulness of combining bladder retention training and behavioral therapy to improve the general maturity and autonomous behavior of the child, and the resultant positive effects on his personality. PMID- 1863929 TI - Malignant choroid plexus papilloma of the IV ventricle. AB - We report a case of malignant choroid plexus papilloma (MCPP) of the IV ventricle in a child with prominent extraventricular expansive growth, mostly into the cerebellopontine angle. Interestingly enough, the tumor was entirely covered by thin, smooth, membranous, fibrous tissue, probably derived from the pia mater. In addition, hydrocephalus was not observed. The reason for the lack of hydrocephalus remains speculative, but it is possible that the presence of pure, nonexpansive, fibrous covering on the tumor might have suppressed the tumor growth to some extent, resulting in progressively increased intratumoral pressure. This, in turn, caused the suppression of excessive cerebrospinal fluid production by the tumor cells. From the diagnostic standpoint, immunohistochemical studies, using antiepithelial membrane antigen (EMA) and antitissue polypeptide antigen (TPA), were demonstrated to be useful for diagnosing the tumor. PMID- 1863930 TI - Congenital forms of intracranial teratoma. AB - Intracranial teratoma in the newborn is a well-recognized but infrequent entity. We describe two such cases: one with a massive intracranial teratoma replacing the cerebral hemispheres and the other, a smaller tumor extending into the orbit. Forms of congenital intracranial teratoma and theories of pathogenesis and management are briefly discussed. PMID- 1863931 TI - Malformations of the spinal cord in 53 patients with spina bifida studied by magnetic resonance imaging. AB - The incidence of associated malformations of the hindbrain and spinal cord in patients with spina bifida was investigated by a clinical and magnetic resonance study. The incidence of these malformations in combination with spina bifida was 49/53 (92.5%). Fifty-tree children born with spina bifida aperta (40 patients) or spina bifida occulta (13 patients) formed the study group. The incidence of the various malformations were: Chiari malformations, type I, 10/53 (19%), and type II, 20/53 (38%); syringomyelia, 13/53 (24.5%); hydromyelia 4/53 (7.5%); tethered cord malformation, 35/53 (66%); diastematomyelia 2/53 (4%). Thirty-seven of the 49 patients with associated malformations had no clinical signs at the time of our study. The results point to the fact that in the pediatric age group, associated spinal defects often remain asymptomatic. PMID- 1863932 TI - Upper extremity function in spina bifida. AB - Poor upper extremity function is often recorded in meningomyelocele patients. Only 2 of the 25 patients we assessed, 5 to 19 years old, showed normal upper extremity function in the clinical neurological examination and a timed hand function test simulating daily activities. Slow performance with unsystematic variability was typical. Poor hand function correlated strongly with hydrocephalus. A trend towards better performance with increasing age may indicate that the difficulties are overcome in some patients. While patients without hydrocephalus showed a near-normal distribution in the seven subtests, patients with hydrocephalus needed more time than normal children. Patients with shunt-treated hydrocephalus did not cope as well as patients without a shunt. Mean age in the three groups differed and may partly explain the differences. PMID- 1863933 TI - Syndromes associated with simple calvarial and complex craniofacial anomalies. AB - Central nervous system (CNS) development is a complex process of predetermined events that must occur in an ordered sequence to ensure normal ontogenesis. Various critical steps take place in a relatively short time (from the first few days to the first months of gestation). Both genetic and environmental insults may produce morphological defects. Early defects often result in nonviable embryos; later, complex craniofacial anomalies, mainly associated with brain damage, may be observed. The pathogenesis of congenital malformations is heterogeneous; sporadic cases are reported as well as recessive or dominant inheritance and chromosomal aberrations. Some of these syndromes have been identified as contiguous gene syndromes; the role of critical chromosomal regions and homeobox genes is discussed. Furthermore, these conditions present difficulties in regard to early diagnosis, surgical repair, and social impact. PMID- 1863934 TI - The influence of head position on the intracranial pressure in preterm infants with posthemorrhagic hydrocephalus. AB - In order to measure the intracranial pressure (ICP) of 8 newborn with posthemorrhagic hydrocephalus (group A) we used the noninvasive technique via the anterior fontanel (Ladd monitor). The ICP was monitored in two different head positions (30 degrees elevated, horizontal). The median measurements were: elevated head position, 13 mm Hg, horizontal head position, 16 mm Hg. For comparative reasons, we also measured the ICP of 12 healthy newborns (group B). The median results were: elevated head position, 4 mm Hg, horizontal head position, 6.5 mm Hg. Significant differences were found between groups. PMID- 1863936 TI - Implications of the reclassification of drugs from prescription-only to over-the counter status. AB - More than 200 over-the-counter (OTC) products and dosage forms were formerly restricted to prescription use. The reclassification process is gaining momentum; another 50 or so prescription drugs are targeted for transfer to OTC status. The transfer of drugs from prescription to OTC status is a logical and systematic development of today's health-care environment. The availability of safe and effective OTC drug products is sure to promote the general health of the American populace and to benefit members of the health-care system across the board. PMID- 1863935 TI - Dandy-Walker malformation: analysis of 38 cases. AB - Thirty-eight cases of Dandy-Walker malformation (DWM) are presented. A female predominance of 3:1 was found. Thirty-two cases (84%) were diagnosed within the 1st year of life. Of these, 17 cases (44.7%) were diagnosed at birth. Ten (26%) were delivered by cesarean section. Thirteen infants (34%) had a birth weight below 3000 g. Several associated malformations were observed, the most frequent being capillary angioma (6 cases); cardiac malformations, ophthalmic anomalies, agenesis of the corpus callosum, malformed limbs, and occipital meningocele were also seen. These observations indicate that DWM represents a disorder of the midline central nervous system indicative of marked genetic and etiologic heterogeneity with the possibility of showing clinical and pathological alterations intra- and extracranially. Macrocephaly was the most frequent physical finding, appearing in 31 cases (82%). Seventeen (44.7%) patients died, 11 before 6 months of age, 3 between 6 and 12 months, and 3 after 1 year. Postmortem studies were performed in 13 patients. Three cases have been lost to follow-up. Mental retardation (IQ below 70) was found in 11 cases (58% of survivors), low intellect (IQ between 70 and 85) in 4, and only 2 patients showed normal intellectual development (IQ more than 85). The high incidence of malformations having several genetic and environmental origins, as well as the high early mortality of patients with DWM, indicate the complexity of this syndrome, which involves the midline developmental field structures. It is not an isolated malformation of the posterior fossa in most cases. PMID- 1863937 TI - Antimicrobial activity of seven oral antibiotics against selected community- and hospital-acquired pathogens. AB - The in vitro activity of seven oral antibiotics (ciprofloxacin, cephalexin, cefaclor, cefadroxil, cefuroxime, cefixime, and amoxicillin/clavulanate) was tested against 355 hospital-acquired pathogens and 342 community-acquired organisms. Whereas Staphylococcus aureus and Escherichia coli were the most common pathogens isolated in community-acquired infections, Enterobacter, Klebsiella, and Pseudomonas were isolated most frequently in hospital-acquired infections. All antibiotics with the exception of cefixime were active against the methicillin-susceptible staphylococci. Ciprofloxacin was the most active antibiotic against the members of the family Enterobacteriaceae and Pseudomonas. The community-acquired organisms tended to be more susceptible to antibiotics than the hospital-acquired organisms. Thus selection of oral antibiotics for the management of patients with hospital-acquired infections should be based on knowledge of the susceptibility patterns of hospital isolates. PMID- 1863938 TI - Availability of soluble insulin in mixed preparations of crystalline and ultralente biosynthetic human insulin. AB - This study investigates potential interactions between human insulins of recombinant DNA origin, specifically ultralente and crystalline Humulin, mixed in different proportions and incubated for five minutes, one hour, or 24 hours. Using insulin mixtures tested within five minutes of preparation, a mixture of less than 50% ultralente insulin produced no reduction in soluble insulin contents, whereas preparations containing greater than 80% ultralente had significantly less soluble insulin content. When premixed insulins were incubated for 24 hours before analysis, the data obtained were similar to the results after five minutes of incubation, although mixtures containing a high proportion of ultralente insulin (greater than or equal to 80% ultralente) retained somewhat more of their regular insulin content after 24 hours of interaction than after five minutes. Studies were also performed after one hour of incubation of insulin mixtures. Soluble insulin was reduced more than at either of the other two time periods investigated. Mixtures that contained greater than or equal to 70% ultralente insulin showed a reduction of greater than or equal to 50% in regular insulin content after one hour of incubation. In intensified insulin therapy programs it is usually recommended that regular insulin be administered separately from animal-source ultralente insulin preparations. The data of the present study clearly demonstrate only minor modifications of soluble insulin activity in clinically common mixtures of human ultralente and regular insulin of recombinant DNA origin. These findings are particularly important for diabetes management protocols that emphasize near normal glycemic control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1863939 TI - Citicoline in the treatment of Parkinson's disease. AB - The subjects were 20 patients with Parkinson's disease. They were aged 52 to 76 years and the duration of the disease ranged from four to 25 years (mean, 12.5 years). All the patients were receiving levodopa alone or in combination with tricyclic antidepressants, amantadine, bromocriptine, anticholinergic agents, or lisuride. Each patient received 1,000 mg of citicoline intramuscularly daily for 15 days and then 500 mg daily for 15 days. After 30 days of treatment, the scores on the Columbia rating scale improved 7.3%; rigidity was improved 18.8%; times to walk 10 m and turn over were reduced 17.5% and 37.4%; and the handwriting test scores improved 19.7%. No side effects were reported. Four patients with advanced parkinsonian symptoms and psychotic side effects received 2,000 mg of citicoline subcutaneously or intravenously for seven days. No improvements in symptoms or treatment side effects were noted. PMID- 1863940 TI - Epidemiology of beta-lactamases in Africa: correlation with resistance to beta lactam antibiotics. AB - In 45 centers from eight African countries, 2,888 bacterial isolates were collected from patients with community-acquired infections. Isolated pathogens included Staphylococcus aureus (29%), Escherichia coli (20%), Neisseria gonorrhoeae (6%), Proteus species (6%), Klebsiella species (6%), Klebsiella pneumoniae (4%), and Staphylococcus epidermidis (4%). An overall sensitivity of 16.2% was shown to penicillin G (number of isolates tested = 2,467), 31.8% to ampicillin (2,687), 45% to amoxicillin (1,959), and 84.9% to cefuroxime (2,888). Beta-lactamase presence was measured by a chromogenic method. Beta-lactamase was found in 75% of all pathogens tested, including 69.5% of gram-negative and 83.3% of gram-positive pathogens; 73% of E coli isolates, 76% of N gonorrhoeae, 75% of Klebsiella species, and 84% of S aureus were beta-lactamase positive. Beta lactamase presence was associated with bacterial resistance for penicillin G, ampicillin, and amoxicillin, but not cefuroxime, whose sensitivity remained high. The higher resistance rates and beta-lactamase prevalence in Africa suggest the need for national antibiotic prescribing policies and surveillance schemes and replacement of relatively ineffective penicillins with newer agents such as cefuroxime. PMID- 1863942 TI - Lincocinamides and the incidence of antibiotic-associated colitis. AB - Reports of antibiotic-associated colitis (AAC) and of pseudomembranous colitis in patients treated with lincocinamides and other antimicrobial agents are reviewed. It is apparent that the incidence of colitis in patients treated with antimicrobials is declining. The greatest risk for AAC is seen in patients treated with ampicillin, followed by the cephalosporins, and then the lincocinamides. Treatment of AAC with vancomycin, metronidazole, or bacitracin is usually effective. PMID- 1863941 TI - Synphasic tablets in Canadian practice: a phase-IV multicenter study. AB - The performance of a low-dose triphasic oral contraceptive (OC) in the first four cycles of use was evaluated by 1,326 primary-care physicians and specialists across Canada in a phase-IV postmarketing trial. Data were available from 5,460 women who completed 19,756 cycles of use with Synphasic. The incidence of intermenstrual bleeding characteristically decreased over the four cycles to 10% in women who were first-time users of OCs, to 14% in women who had previously used OCs but had discontinued use until this trial, and to 16% in women who had switched from another OC to Synphasic. The women reported a low incidence of headache, nausea, weight gain, breast complaints, and acne while receiving Synphasic. The results demonstrate good endometrial control with Synphasic and a high level of patient acceptance. PMID- 1863943 TI - Josamycin in the treatment of bronchopulmonary infections. AB - The subjects were 6,033 outpatients, from every province of Spain, with acute bronchitis (44%), exacerbation of chronic bronchitis (35%), typical pneumonia (14%), or atypical pneumonia (8%). Most of the patients were aged 50 to 70 years. The dose of josamycin in over 90% of the patients was 2 gm daily. The mean duration of infection before treatment was 5.3 days and treatment lasted a mean of 9.2 days. Concomitant drugs were taken by 78% of the patients; these included mucolytic agents, xanthine derivatives, beta-adrenergic agonists, and corticosteroids. After two weeks of treatment, the infection was cured in 82% of the patients with acute bronchitis, in 30% with chronic bronchitis, in 85% with typical pneumonia, and in 85% with atypical pneumonia; improvement was shown by 16%, 66%, 13%, and 13%, respectively. Treatment side effects were noted in 11% of the patients receiving josamycin alone and in 17% of the patients receiving concomitant drugs. Most side effects were mild and transient; treatment was discontinued because of side effects in 2% of the patients receiving josamycin alone and in 3% receiving concomitant drugs. It is concluded that josamycin is a safe and effective agent in the treatment of bronchopulmonary infections. PMID- 1863944 TI - Basic principles of cardioplegic management in donor heart preservation. AB - The primary factor limiting the number of heart transplantation performed is the lack of adequate donor hearts. One of the main factors contributing to this is the relatively short period a donor heart can be preserved. Clinical studies demonstrate that ischemic times over five hours lead to early heart failure after transplantation. A considerable increase in preservation time would be necessary to enlarge the donor pool. In spite of intensive research, it is not yet possible to increase the preservation period above four hours, which was achieved in 1978. An increase of the cold ischemia period to more than four hours without the risk of transplanted heart damage may only be achieved by improving cardioplegic management. PMID- 1863945 TI - The efficacy and tolerability of famotidine and ranitidine on the healing of active duodenal ulcer and during six-month maintenance treatment, with special reference to NSAID/aspirin-related ulcers. AB - The subjects of this multicenter study were 160 patients with endoscopically confirmed active duodenal ulcers, randomly assigned to receive 40 mg of famotidine or 300 mg of ranitidine nightly for four to eight weeks. During a subsequent six-month maintenance treatment phase, the patients received 20 mg of famotidine or 150 mg of ranitidine nightly. After eight weeks of treatment, ulcer healing was endoscopically confirmed in 94% of the 81 famotidine-treated patients and in 80% of the 79 ranitidine-treated patients (P less than 0.01). During the first week of treatment, daytime and nighttime pain scores were significantly lower in the famotidine-treated than ranitidine-treated patients. During the maintenance treatment phase, the ulcer in 79% of 58 famotidine-treated patients and in 81% of 52 ranitidine-treated patients remained healed. Multivariate analysis of factors such as age, sex, smoking, alcohol and coffee consumption, use of nonsteroidal anti-inflammatory drugs (NSAIDs), history of ulcer, and ulcer size and number showed that they had no significant effects on the differences in healing rates between the two treatment groups. The ulcers were all healed in the famotidine-treated patients whose ulcers were associated with the prior use of NSAIDs. The results of this and many other studies indicate that, unless ulcer healing is confirmed by endoscopy, treatment of active duodenal ulcers should continue for six to eight weeks. PMID- 1863946 TI - Milestones in clinical pharmacology. Oral hypoglycemic agents: sulfonylurea. PMID- 1863947 TI - [Observation on clinical features and therapy in 4 elderly cases with legionellosis]. AB - Four elderly cases with Legionellosis were reported. All of them had pneumonitis and small amount of chest fluid. Erythromycin and rifadin were effective in all 4 patients. Three patients were positive for Legionella pneumophila serogroup 1. The disease occurred in July or October. Diagnosis and therapy should be made as early as possible for those patients suspected of Legionellosis. PMID- 1863948 TI - [Geographic distribution of Lyme disease in Mudanjiang]. AB - Four forestry plant in Mudanjiang with different geographic characteristics were investigated in 1989. 2178 people were inquired and examined. 74 cases including 54 of ECM, 12 of nervous system disorder and 8 of arthritis were confirmed as Lyme disease. There were some patients at other places of forest areas of Mudanjiang. The prevalence rate of Lyme disease ranged from 1% to 4.5% at four plants with higher rate in mountainous area than in hilly land. It is first report that one strain of Lyme disease spirochetes was isolated from a patient with psychiatric derangement. It proved that Ixodes persulcatus play the leading role in transmission of Lyme disease spirochetes, as the growth curve of Ixodes persul catus is coincident with that of the patient with ECM. PMID- 1863949 TI - [The mortality of patients with malignant tumors in eleven cities of Jiangsu Province, 1984-1986]. AB - The present paper analysed people in eleven cities making up one sixth of Jiangsu population. In 1984-1986 the mortality of malignant neoplasm was 163.28/10(5), (Chinese standard mortality were 116.57/10(5), the world standard mortality were 177.75/10(5)) which accounts for 25.04% of the total mortality during the same time. The trends of deaths from neoplasms show that oesophageal cancer in both sexes and leukemia in male are gradually decreasing, lung cancer in male and hepatoma in female are gradually increasing. The rank correlation analysis between chinese standard mortalities of some major malignant neoplasms indicates that the stomach cancer was positive correlated with oesophageal cancer in both sexes, the oesophageal cancer in male and the stomach cancer in female were negative correlated with lung cancer, and the breast cancer was negative correlated with oesophageal cancer in female. All this suggests that there may be likely etiologic association between these malignant neoplasms. PMID- 1863950 TI - [A case-control study of peptic ulcer risk factors: smoking]. AB - The 1:1 matched case-control study was undertaken. The associated risk factors such as smoking etc were investigated. Three hundred cases of peptic ulcer and 300 controls individually matched were interviewed. Conditional logistic regression was employed to examine the effect modification. The analytic results showed that Smoking, family history, nutrition, anxiety and depression were the risk factors of peptic ulcer. No relation was found between blood types and peptic ulcer. PMID- 1863951 TI - [Epidemiology of hypertension]. PMID- 1863952 TI - [Use of multilocus enzyme electrophoresis for bacterial population genetics, classification and molecular epidemiology]. PMID- 1863953 TI - Does use of a vascular introducer sheath obviate need for catheter exchanges over a guidewire? PMID- 1863954 TI - Balloon diameter of the Inoue balloon catheter during percutaneous transvenous mitral commissurotomy: clinical and experimental study. AB - To determine adequate and effective balloon diameters of the Inoue balloon catheter, we reviewed clinical results and characteristics of the Inoue balloon catheter, especially the relationship between the intra-balloon pressure and the balloon diameter, experimentally and clinically, in 46 patients with mitral stenosis undergoing percutaneous transvenous mitral commissurotomy (PTMC). Mitral valve area increased from 1.1 +/- 0.3 to 2.1 +/- 0.3 cm2 in all patients after PTMC. Based on balloon diameter settings, mitral valve area increased from 1.3 +/ 0.4 to 2.3 +/- 0.5 cm2 in patients treated with a balloon setting greater than 26 mm in diameter, from 1.1 +/- 0.3 to 2.0 +/- 0.5 cm2 in patients with a balloon setting at 26 mm in diameter, and from 1.1 +/- 0.4 to 1.7 +/- 0.4 cm2 in those treated with a balloon setting less than 26 mm in diameter, with an increase in mitral valve area of 1.0 +/- 0.6, 0.9 +/- 0.4, and 0.7 +/- 0.2 cm2, respectively. There was a significant difference between the increase in mitral valve area at a setting of 26 mm in diameter and that observed at a setting less than 26 mm in diameter. We next investigated differences between balloon diameter settings and actual balloon diameters measured from cineangiograms at maximum balloon inflation. The ratio of actual balloon diameter to a setting diameter of less than 26 mm was smaller than that of 26 mm. To evaluate the reason for the difference, we investigated the relationship between intra-balloon pressure and balloon diameter. In the prototype Inoue balloon catheter, intra-balloon pressure increases from 1.0 kg/cm2 at 20 mm in diameter to 2.2 kg/cm2 at 30 mm in diameter at atmospheric pressure. In conclusion, the increase in mitral valve area was inadequate when the balloon was less than 26 mm in diameter because of inadequate intra-balloon pressure. We, therefore, recommend a balloon size set above 26 mm to obtain adequate intra-balloon pressure when using the Inoue balloon catheter. PMID- 1863955 TI - Crossing failure in PTCA: mind the deflated balloon profile! AB - An attempt to reposition an Integra PTCA balloon-on-a-wire failed although the whole stenosed segment could be crossed before inflation. After careful removal the device showed a grossly altered shape. Deflated balloon profiles, quite different from the initial shape, can determine the outcome both in dissections and in multilesion cases. PMID- 1863956 TI - Successful percutaneous closure of a complex coronary-to-pulmonary artery fistula using a detachable balloon: benefits of intra-procedural physiologic and angiographic assessment. AB - A 48-yr-old woman presented with a loud continuous precordial murmur and symptoms of fatigue. Color-flow doppler imaging and nuclear magnetic resonance imaging failed to show the cause of the murmur. Diagnostic catheterization showed a large left anterior descending coronary artery to pulmonary artery fistula with impaired left ventricular wall motion. Two detachable balloons were deployed in the fistula with complete abolition of flow in the main fistula channel. A small parallel channel of the fistula, previously not appreciated due to vessel overlap, remained patent but had trivial flow as assessed by green-dye and oximetric techniques. The patient had immediate resolution of her symptoms and return of normal ventricular wall motion. PMID- 1863957 TI - Left main coronary artery aneurysm in association with severe atherosclerosis: a case report and review of the literature. AB - Aneurysms of the coronary arteries occur in from 0.3% to 4.9% of angiograms. Only 12 cases of left main artery (LMA) aneurysms have been reported. Of these, seven were associated with atherosclerosis in patients more than 56 years old. This report details the case of a 39-year-old patient with a large LMA aneurysm associated with atherosclerosis. PMID- 1863958 TI - Coronary angioplasty in octogenarians: comparisons to coronary bypass surgery. AB - Coronary angioplasty was performed in 74 patients 80 years of age and older (mean 83 +/- 3). Single vessel coronary disease was present in 34% and multivessel coronary disease in 66%. Angioplasty of a single vessel was performed in 51 patients (69%), while 23 (31%) had angioplasty of multiple vessels. Angioplasty was successful in 59 of 74 patients (80%). Angioplasty was unsuccessful but uncomplicated in 12 (16%) due to (unyielding) calcified lesions or (impassable) old occlusions. Of these 12, 8 were discharged on medical therapy and 4 underwent elective uncomplicated bypass surgery prior to discharge. Three (4%) patients required emergency coronary bypass surgery due to abrupt vessel closure during the angioplasty procedure, with one hospital death (1.4%). Follow-up (mean 24 +/- 22 months) was obtained in all patients. Of the 59 successful angioplasty patients, late mortality was 10% (cardiac 7% and non-cardiac 3%). Survival and survival without myocardial infarction were both 90%; survival without either infarction or bypass surgery was 86%. Actuarial 3-year survival was 91% and 3 year freedom from death, infarction or bypass surgery was 87% by life-table analysis. Repeat angioplasty for restenosis was performed in 7 patients (12%) without complications. PMID- 1863959 TI - Cerebral ischemia: a complication of right ventricular endomyocardial biopsy. AB - During percutaneous transvenous endomyocardial biopsy, two cardiac transplant recipients developed symptoms of focal cerebral ischemia. Cerebrovascular injury has not been previously associated with endomyocardial biopsy. This procedure should be recognized as one of the causes of stroke following heart transplantation. PMID- 1863960 TI - Multivessel PTCA using the hugging balloon technique based on single guide catheter and dual balloon-on-a-wire systems. AB - For percutaneous transluminal coronary angioplasty (PTCA) of oversized arteries, often-times a satisfactory dilatation cannot be achieved with conventional balloon systems due to the unavailability of adequately sized balloons. This fact has contributed to a higher restenosis rate for this group of patients. We were able to obtain a satisfactory dilatation result in an oversized right coronary artery with a shepherd's crook configuration and eccentric anatomy at the origin using two balloon-on-a-wire systems and an Amplatz type guiding catheter. Although such favorable dilatation of an oversized artery using this "hugging balloon technique" can be expected, issues do exist such as difficult maneuverability and estimation of the balloon size obtained through simultaneous dual balloon inflation wherein size does not simply equal the sum of the two balloon catheters. It is hoped that there will be further improvements of the technique and development of new systems. At this time, however, it is felt that this is the most effective and reasonable strategy to achieve a high chance of success in oversized vessel lesions. PMID- 1863961 TI - Concurrent double balloon valvotomy for combined rheumatic mitral and tricuspid stenosis. AB - We expanded the application of percutaneous balloon valvotomy (PBV) to 4 adults (age 14 to 30 years, average 22.2 years) with combined rheumatic mitral and tricuspid stenosis. Double balloon dilatation reduced the transmitral gradient from 17.36 +/- 3.54 to 5.52 +/- 0.89 (P less than 0.025) and transtricuspid gradient from 12.65 +/- 2.67 to 3.67 +/- 0.95 (P less than 0.025). Mitral and tricuspid valve area increased from 0.73 +/- 0.20 to 2.57 +/- 0.67 (P less than 0.005) and from 0.77 +/- 0.24 to 2.67 +/- 0.24 cm2 (P less than 0.005), respectively. The procedures were well tolerated, with no significant increase in valvular regurgitation or left to right shunt across the atrial septum. The excellent symptomatic and haemodynamic benefits are sustained at 3-24 months follow-up. It is concluded that combined dilatation of stenotic valves by double balloon technique can emerge as an alternative to surgery in selected patients with polyvalvar rheumatic heart disease. PMID- 1863962 TI - The kissing balloon technique with two over-the-wire balloon catheters through a single 8-French guiding catheter. AB - Some of the newer over-the-wire coronary angioplasty catheters have shaft sizes of 3.0 French (F) or less. The inner diameter of modern 8-F guiding catheters is large enough to accommodate two of such balloon catheters. We report a kissing balloon procedure with two over-the-wire catheters through a single 8-F guiding catheter. PMID- 1863963 TI - Interpretation of cardiac physiology from pressure waveform analysis: extra hearts: Part III. PMID- 1863964 TI - A new technique for sheathless percutaneous intraaortic balloon catheter insertion. AB - Intraaortic balloon counterpulsation is helpful for controlling myocardial ischemia and providing hemodynamic support, but its applicability is limited by lower extremity ischemic complications in a significant percentage of patients. We developed a new sheathless technique for percutaneous intraaortic balloon catheter insertion which reduces the effective catheter diameter. A pilot study using this new technique resulted in a 10% rate of limb ischemia, without compromise of balloon function. We conclude that this technique may be useful in reducing the incidence of limb ischemia associated with intraaortic balloon counterpulsation. PMID- 1863965 TI - Evaluation of the densitometric method of ejection fraction by direct digital subtraction left ventriculography. AB - The aim of the present study was to test the hypothesis that the densitometric ejection fraction (EF) could be calculated by direct contrast digital subtraction left ventriculography in a single heartbeat. Thirty patients underwent direct contrast digital subtraction left ventriculography and biplane conventional left ventriculography. The values of EF were obtained from digital subtraction ventriculograms of the first cardiac cycle after completion of the injection of the contrast medium by the videodensitometric technique and were compared with those obtained from conventional ventriculograms by the area-length method in the same patients. There was a close correlation between the densitometric EF from digital subtraction ventriculograms and the volumetric EF from conventional ventriculograms (r = 0.78). Densitometric EF measured in the 30 degree right anterior oblique projection highly correlated with densitometric EF measured in the 60 degree left anterior projection (r = 0.98). These data suggest that this densitometric technique is available in any projection and is a simple procedure for the accurate measurement of left ventricular EF. PMID- 1863966 TI - Complication of coronary arteriography. PMID- 1863967 TI - Precertification for PTCA. PMID- 1863968 TI - Salivary gland enlargement following renografin injection may be secondary to hypersensitivity. PMID- 1863969 TI - The evolution and ethics of dentistry's dilemma. PMID- 1863970 TI - How much is enough? PMID- 1863971 TI - Buying and selling for the established dentist. PMID- 1863972 TI - Success by design. PMID- 1863973 TI - Analysis of a functional appliance. PMID- 1863974 TI - Asset allocation for the dentist. PMID- 1863975 TI - Hard tissue and home tooth whiteners. PMID- 1863976 TI - Selling tips for the retiring dentist. PMID- 1863977 TI - Successful marketing on a shoestring. PMID- 1863978 TI - Post-core construction: the holistic approach. PMID- 1863979 TI - Looking for that financial needle in the haystack. PMID- 1863980 TI - Biotransformation of halogenated compounds. AB - As a result of natural production and contamination of the environment by xenobiotic compounds, halogenated substances are widely distributed in the biosphere. Concern arises as a result of the toxic, carcinogenic, and potential teratogenic nature of these substances. The biotransformations of such halogenated substances are reviewed, with particular emphasis on the biocatalytic cleavage of the carbon-halogen bonds. The physiology, biochemistry, and genetics of the biological system involved in the dehalogenation reactions are discussed for three groups of organohalogens: (1) the haloacids, (2) the haloaromatics, and (3) the haloalkanes. Finally, the biotechnological applications of these microbial transformations are discussed. This includes prospects for their future application in biosynthetic processes for the synthesis of halogenated intermediates or novel compounds and also the use of such systems for the detoxification and degradation of environmental pollutants. PMID- 1863981 TI - The application of biotechnology to the treatment of wastes produced from the nuclear fuel cycle: biodegradation and bioaccumulation as a means of treating radionuclide-containing streams. AB - Recent concerns on the radiotoxicity and longevity of nuclides have prompted the development of new technologies for their removal from wastes produced from nuclear power programs and nuclear fuel reprocessing activities. Alongside developments from traditional chemical treatment processes, interest has also centered on the application of biotechnology for efficient waste treatment. Many biological techniques have relied on empirical approaches in simple model systems, with scant regard to the nature and volume of actual target wastes; such considerations may limit the application of the new technologies in practice. This review aims to identify some of the likely problems, to discuss the various approaches under current consideration, and to evaluate ways in which either the target waste or the detoxifying biomass may be modified or presented for the most efficient treatment. PMID- 1863982 TI - A monoclonal antibody recognizing a common antigen on Drosophila embryos and human fibroblasts. AB - We used a monoclonal antibody specific for vimentin from human fibroblasts to stain whole mounts of Drosophila embryos. In immunofluorescence observations this antibody cross-reacts with an antigenic determinant localized throughout mitosis at the nuclear boundary. Double fluorescence observations with the Rb188 antibody that specifically recognizes a centrosomal protein of the Drosophila embryo [Whitfield et al., 1988] showed that the anti-vimentin antibody cross-reacts with an antigen localized in the centrosomal region. PMID- 1863983 TI - Isolation and localization of a spectrin-like protein from echinoderm sperm. AB - Thyone sperm undergo an explosive acrosome reaction resulting in the extension of a 90 microns long acrosomal process. In unreacted sperm, profilamentous actin is sequestered within the profilactin cup (Tilney: Journal of Cell Biology 69:73-89 1976), which consists of four major polypeptides: actin, profilin, and a 250/235 kDa equimolar doublet (TS 250/235). Dialysis of profilactin preparations into an actin assembly buffer resulted in the formation of acrosomal-like macromolecular aggregates containing actin, TS 250/235, and several other polypeptides as detected by SDS-PAGE. TS 250/235 was purified by subjecting extracts of pH solubilized profilactin cups to DEAE and phosphocellulose ion exchange chromatography. TS 250/235 demonstrated immunocrossreactivity with affinity purified polyclonal antibodies raised against S. purpuratus egg spectrin. As determined by biotinylated-calmodulin overlays, both subunits of TS 250/235 bound calmodulin in a Ca(++)-sensitive manner. Electron microscopy of low angle, rotary shadowed replicas of TS 250/235 revealed an elongate rod-shaped molecule with an average contour length of 203 nm. By indirect immunofluorescence, TS 250/235 was found to be uniformly distributed throughout the profilactin cup of the unreacted sperm. This distribution of TS 250/235 correlated with the location of monomeric actin as determined by localization studies utilizing fluorescent-DNase-1. Upon sperm activation, the cellular distribution of TS 250/235 dramatically changed and was observed both along the length and at the base of the extended acrosomal process. PMID- 1863984 TI - Alterations in microtubule assembly caused by the microtubule-active drug LY195448. AB - LY195448 is an experimental drug that blocks cells at metaphase (Boder et al.: Microtubules and Microtubule Inhibitors 1985: 353-361, 1985). A 4 hour exposure of NRK cells to a drug concentration of 46 microM (15 micrograms/ml) increased the number of mitotic cells in the population from 4.9% to 18.5%. Examination of treated cells by immunofluorescence showed increased numbers of cells blocked at prometaphase, with short microtubules extending from the spindle pole to the kinetochores. The cytoskeleton of interphase cells remained intact at these concentrations. However, the number of microtubules appeared to be reduced, and those that remained appeared kinkier and curled, particularly toward the periphery of the cells. When cytoskeletal microtubules of NRK cells were depolymerized with nocodazole, they reassembled within minutes of transfer to drug-free media. However, nocodazole-treated cells transferred to fresh media containing 15 micrograms/ml of LY195448 required 2-3 times longer to reassemble cytoplasmic microtubules. Previously isolated Chinese hamster ovary cell microtubule mutants resistant to either taxol or Colcemid were tested for cross resistance to this drug. Cell lines resistant to the depolymerizing drug Colcemid exhibited increased resistance to LY195448 compared to wild-type cells, whereas taxol resistant cell lines were more sensitive. Of eleven newly isolated mutant CHO cell lines selected for increased resistance to LY195448, seven exhibited an altered beta-tubulin protein by two-dimensional polyacrylamide gel electrophoresis. These 11 cell lines also showed a heterogenous pattern of resistance to several microtubule-active drugs. These data demonstrate that LY195448 is cytotoxic to mammalian cells because it inhibits microtubule assembly, most likely through a direct interaction with tubulin. PMID- 1863985 TI - Analysis of immunoglobulin and T cell receptor genes. Part I: Basic and technical aspects. PMID- 1863987 TI - Personality in 47, XXY males during adolescence. AB - The responses to the High School Personality Questionnaire and the Million Adolescent Personality Inventory of a series of neonatally identified 47, XXY adolescent males and age-matched controls were compared. The extra X males' results indicated that they were more assertive, impulsive and prone to conflict than controls. Individual differences in these characteristics among the extra X cases had little relationship to quality of parenting but were related to indices of pubertal development. PMID- 1863986 TI - Analysis of immunoglobulin and T cell receptor genes. Part II: Possibilities and limitations in the diagnosis and management of lymphoproliferative diseases and related disorders. PMID- 1863988 TI - Gene deletions in Japanese patients with Duchenne and Becker muscular dystrophies: deletion study and carrier detection. AB - Fifty unrelated Japanese patients with Duchenne and Becker muscular dystrophy (DMD and BMD) have been studied through use of the dystrophin cDNA probes. The 14 kb dystrophin cDNA was subdivided into six subclones, and Hind III-digested DNAs were analyzed by Southern blotting. Of 50 unrelated patients, 20 showed a deletion of one or several of the exon-containing Hind III fragments (40.0%). These corresponded to 50% (11/22) of BMD patients and 32.1% (9/28) of DMD patients, and the position and extent of deletions were mapped and proven to be more heterogeneous in DMD than in BMD. Both ends of deletions detected by probe 1 2a were common to all six BMD patients, and the 5' ends of deletions in probe 5b 7 were also common to four BMD patients. The phenotypic-specific deletion in Japanese BMD patients existed in the 5' end of the DMD gene, although an apparently similar deletion produced a wide range of clinical courses (BMD phenotype). Three out of eight females in DMD/BMD families were diagnosed as carriers through use of the junctional fragment and dosage analyses of dystrophin cDNA. PMID- 1863989 TI - Estimates of heritability of plasma homocyst(e)ine levels in aging adult male twins. AB - Plasma homocyst(e)ine level was determined for 96 identical (MZ) and 92 fraternal (DZ) adult male twins aged 59-69. There was no difference in mean between MZ (10.31 nmol/ml) and DZ (10.36 nmol/ml) twins. The intraclass correlation coefficient of the log-transformed homocyst(e)ine level in 43 complete MZ and 39 complete DZ pairs was 0.55 and 0.19, respectively. The MZ correlation was significantly (p less than 0.05) greater than the DZ correlation, suggesting that the level of plasma homocyst(e)ine is genetically influenced. PMID- 1863990 TI - Molecular identification of a small supernumerary marker chromosome by in situ hybridization: diagnosis of an isochromosome 18p with probe L1.84. AB - A dysmorphic child was found by cytogenetic analysis to have an extra small marker chromosome. The marker chromosome was shown to possess a chromosome 18 centromere by in situ hybridization, and probably represents an isochromosome 18p. Centromere specific probes should be of value in identifying extra small marker chromosomes, and thereby provide better understanding of the clinical significance of these. PMID- 1863991 TI - A clinical, cytogenetic and familial study of 307 mentally retarded, institutionalized, adult male patients with special interest for fra(X) negative X-linked mental retardation. AB - In this study we report the results of a systematic etiological, clinical genetic study in 307 institutionalized mentally retarded adult males. Special attention is paid to the nosology of X-linked mental retardation. During the survey 63 males with one or more 'Martin Bell'-like features were identified in whom repetitive fragile Xq27-3 screenings were negative. In 13 of them, belonging to 9 different families, pedigree data were compatible with X-linked inheritance. This finding confirms the existence of one (or more) forms of fra(x) negative mental retardation with 'Martin Bell'-like features. PMID- 1863992 TI - Malformations in a child with dup (7pter-p15.1) and del (7q36-qter) as a result of familial pericentric inversion. AB - We describe a child with multiple anomalies and severe retardation with dup 7pter p15.1 and del 7q36-qter as a result of a parental pericentric inversion of chromosome 7. The pericentric inversion was found in family members in 3 generations with 9 liveborn children who had severe anomalies probably associated with imbalances of chromosome 7. PMID- 1863993 TI - DNA deletions in the low density lipoprotein (LDL) receptor gene in Danish families with familial hypercholesterolemia. AB - DNA samples from 25 unrelated Danish patients with familial hypercholesterolemia (FH) were screened by Southern blot hybridization to detect gross alterations in the low density lipoprotein (LDL) receptor gene. Three FH-patients were found to have a deletion. Two of these delete part of the cysteine rich domain, which comprises the ligand binding region of the LDL-receptor. The third deletion encompasses coding regions for the cytoplasmic part of the receptor. As two of these deletions could be equivalent to previously described LDL-receptor gene alterations, these data seem to support a notion of recombination hot spots which involve Alu-sequences. PMID- 1863994 TI - Second case report of del(4) (q25q27) and review of the literature. AB - We report a malformed infant with a de novo interstitial deletion of 4q. This is the second patient reported with del(4) (q25q27). Although there are several common features such as marked hypotonia, cardiac abnormalities, cleft palate, and micrognathia noted in our case and that of Chudley et al. (1988), we conclude from our comparison of the seven previously reported cases involving deletions of bands 4(q25q27) that a specific phenotype cannot yet be described for this deletion. PMID- 1863995 TI - Prenatal diagnosis of lethal osteogenesis imperfecta in twin pregnancy. AB - Lethal osteogenesis imperfecta was diagnosed at 27 weeks amenorrea in one fetus of a bichorial twin pregnancy. Sonographic findings included: short-limb dwarfism, hypotrophy and hypoechoic bones. The affected fetus was so translucent that only the normal fetus could be seen on plain in utero radiography. The affected fetus died immediately after birth. Postmortem radiography and histology were typical of lethal osteogenesis imperfecta of type IIA. Aids to the etiological diagnosis of in utero dwarfism are presented. Sonographic features correlated with neonatal death are described. PMID- 1863996 TI - Atelosteogenesis I and boomerang dysplasia: a question of nosology. AB - We report a patient whose clinical, radiologic and histopathologic findings are compatible with severe atelosteogenesis (AT-I). The patient is compared with previously reported cases of AT-I, as well as with patients reported as having "boomerang" dysplasia. We conclude that it is reasonable to consider AT-I and boomerang dysplasia as part of a spectrum, probably reflecting a common etiology. More and detailed clinical, radiologic and histopathologic reports are needed to further clarify the relationship of AT-II and AT-III in this family of skeletal dysplasias. PMID- 1863998 TI - Clinical efficacy of intravenous immunoglobulin in patients with severe inflammatory chest disease and IgG3 subclass deficiency. AB - To investigate the efficacy of i.v. IgG treatment in pediatric patients with inflammatory lung disease, a prospective, controlled clinical trial was carried out over a 2-year study period. Patients were enrolled on the basis of severe clinical symptomatology. After 1 year of conventional treatment, the patients received 400 mg/kg per month of an i.v. IgG product containing only trace amounts of IgG3 in addition to their regular treatment throughout the second year. Significant clinical improvement, as documented by duration of hospital stay (first year 27.8 days, second year 4.9 days), use of antibiotics (132.8 versus 30.9 days) and use of steroids (21.4 versus 0.7 days) could be observed. Data obtained on a subgroup of patients with IgG3 deficiency were analysed separately. These results indicate that patients with severe chest disease who have IgG3 deficiency will also benefit from i.v. IgG treatment. The mode of action cannot be attributed to replacement of the respective isotypes, but is probably due to the effect of i.v. IgG in preventing repeated viral infections. PMID- 1863997 TI - Genetics of human X-linked immunodeficiency diseases. PMID- 1863999 TI - Defects in proliferative responses of T cells from patients with common variable immunodeficiency on direct activation of protein kinase C. AB - DNA synthesis in response to mitogens has been studied in T cells from nine patients with common variable immunodeficiency (CVI) and seven normal individuals. Five out of the nine patients had cells with subnormal responses to the mitogen phytohaemagglutinin (PHA). As PHA-induced responses are largely mediated through activation of Ca(2+)-dependent protein kinase C, we studied whether the defective response was still present on direct activation of protein kinase C. This was done using combinations of concentrations of phorbol 12,13, dibutyrate and the calcium ionophore ionomycin which induced proliferation in normal T cells. We found that in CVI patients with T cells which had normal responses to PHA, responses to phorbol ester and ionomycin were at the same level as in normal T cells. However, with this treatment, in which the linkage between the membrane receptor and protein kinase C is bypassed, the level of DNA synthesis was still depressed in the patient group whose T cells had subnormal responses to PHA. IL-2 failed to restore the DNA synthesis to normal levels when added with the phorbol ester and ionomycin to T cells from one patient in this group. These data suggest that in a group of CVI patients there are defects in T cell activation pathways at or down-stream of protein kinase C. PMID- 1864000 TI - Immunophenotypic analysis of histiocytes involved in AIDS-associated Mycobacterium scrofulaceum infection: similarities with lepromatous lepra. AB - The present study reports a rare case of systemic M. scrofulaceum infection in an AIDS patient and analyses the inflammatory infiltrate in a lymph node by immunohistochemistry. Special emphasis is put on the histiocytes. The diffuse infiltrate consists mainly of large histiocytes that contain numerous bacilli. These cells display the phenotype of mature histiocytes and in addition coexpress the antigens recognized by RFD7 and RFD9, both markers of different subsets of histiocytes which have been reported to be co-expressed by the infected histiocytes in the infiltrate of lepromatous lepra. Interdigitating reticulum cells are rare as well as T cells which are mainly of the suppressor/cytotoxic type. These findings are similar to those reported for lepromatous lepra and might indicate common deficiencies in T cell-macrophage interactions in both conditions. Superimposed on the diffuse infiltrate of large histiocytes we observed 'monocytic granulomas', the presence of which might be related to a reactional state comparable to erythema nodosum leprosum, a reactional state of lepromatous lepra. PMID- 1864001 TI - T and B cell human responses to European bat lyssavirus after post-exposure rabies vaccination. AB - T and B cell human responses to European bat lyssavirus (EBL1) induced by post exposure rabies vaccination (PM virus vaccine) were evaluated by measuring plasmatic titres of EBL1-specific neutralizing antibodies; specific EBL1-binding antibodies; and proliferation indices of peripheral blood lymphocytes stimulated in vitro with EBL1. These parameters for vaccination efficacy were compared with those obtained with vaccine-related viruses (CVS and ERA) and with a non-vaccine related virus. Mokola virus, the last implicated in vaccination failures. Twenty two patients exposed to rabies risk who received a reduced rabies post-exposure vaccination were involved in the study. On day 21, vaccine induced CVS-specific neutralizing antibodies in all patients; but EBL1-specific neutralizing antibodies were induced in only 73% of patients. No vaccine had Mokola-specific neutralizing antibodies. Patients having EBL1-specific neutralizing antibodies were usually those in whom vaccination induced high titres of CVS-specific neutralizing antibodies. On day 21, peripheral blood lymphocytes of 86% of patients could be restimulated in vitro with vaccine, 43% with EBL1 and 45% with Mokola. Patients exhibiting a high vaccine-specific proliferation response more likely developed an EBL1- or a Mokola-specific proliferative response. No correlation was found between T and B cell responses. Rabies vaccination induced neither T nor B cell EBL1-specific responses in 22% of patients. PMID- 1864002 TI - New Zealand black mice are immunologically resistant to high-dose, but not low dose Leishmania mexicana infection. AB - The course of infection following s.c. inoculation of a wide dose range of L. mexicana stationary-phase promastigotes (SPP) was examined in sexually mature and immature NZB mice of both sexes. Infection with a high dose (greater than 10(7) SPP) was able to induce a protective in vivo response, which could be adoptively transferred with parasite-immune T cells, into naive, syngeneic recipients. In contrast, s.c. infection with a low dose (less than 10(7) SPP) induced non healing lesions; disease susceptibility could also be transferred into naive animals with T cells from non-immune donors. When the ability to mount a delayed type hypersensitivity (DTH) reaction was tested in these two groups, the high parasite dose group gave a significantly higher response. The in vivo protection and high DTH response were reflected in the ability of cells derived from the high-dose resistant (but not low-dose susceptible) mice to mount an antigen specific T cell response in vitro. The possible immunological effector mechanisms underlying high-dose resistance and low-dose susceptibility are discussed. PMID- 1864003 TI - The gene corresponding to the putative Goodpasture antigen is present in Alport's syndrome. AB - Alport's syndrome is a heterogeneous group of inherited abnormalities of basement membranes that may result in progressive renal failure, defective hearing and lens abnormalities. The glomerular basement membrane (GBM) characteristically has areas of reduplication, lamellation and attenuation on electron microscopic examination. In the majority of affected males and some females, there is reduced or variable binding of serum from patients with anti-GBM disease (Goodpasture's syndrome) to these basement membranes. These sera contain antibodies directed against the Goodpasture antigen which has been thought to be located in the non collagenous domain of the alpha3 chain of type IV collagen and is presumed to be important in cross-linking of the collagen molecules. The reduced staining for the Goodpasture antigen suggests that this structure is either absent or masked in Alport's syndrome. We have tested DNA from six unrelated individuals with Alport's syndrome. All had been transplanted for renal failure. The diagnosis of Alport's syndrome was made on the characteristic electron microscopic appearance of the renal basement membranes (n = 4), the presence of sensori-neural deafness (n = 4), a family history of Alport's syndrome (n = 5) and the presence of circulating inhibitable anti-GBM antibody activity post-transplant (n = 2). Oligonucleotides (20mers) corresponding to the 5' and 3' ends of the known 25 amino acid sequence for the putative Goodpasture antigen were used as primers for amplification of genomic DNA. The products were then blotted and probed with an intermediate 19-mer DNA. All Alport's patients contained a 75-bp fragment corresponding to the published peptide sequence for the non-collagenous domain of the alpha 3 chain of type IV collagen, suggesting that a large deletion of this region, the putative Goodpasture antigen, is unlikely to account for the defect in Alport's syndrome. PMID- 1864004 TI - Detection of DNA-bound immunoglobulins in patients with lupus nephritis, using monoclonal anti-DNA antibody. AB - In order to investigate the relationship between renal histopathology and the characteristics of circulating immune complexes (CICs) in patients with lupus nephritis (LN), we measured the sizes of CICs, DNA-bound immunoglobulins in patients with systemic lupus erythematosus (SLE) and different histopathological forms of nephritis. Sera were obtained from nine patients: four with diffuse proliferative LN (DPLN), four with membranous LN (MLN), and one with mesangial LN, who fulfilled the criteria of the American Rheumatism Association for SLE. The DNA-bound immunoglobulins were measured by ELISA, in which ELISA plates were coated with mouse monoclonal anti-DNA antibodies. The sizes of CICs were analysed by sucrose density gradient ultracentrifugation. Large (larger than 19S), intermediate (19-7S) and small (nearly 7S) sized DNA-bound immunoglobulins (high peaks of IgG and IgA, but low IgM peaks) were found in the patients with DPLN. By contrast, in patients with MLN, the sizes of ICs; DNA-bound IgG, IgA were in general slightly larger than 7S. In one patient with DPLN, at the onset, various sized DNA-bound IgG, IgA and IgM were found. After the methylprednisolone pulse therapy, CICs became smaller and gradually disappeared. We conclude that the characteristics of DNA-anti-DNA IgG, IgA complexes may determine the localization of ICs in the glomeruli and suggest that CICs play an important role in the pathogenesis of LN. PMID- 1864005 TI - Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis. AB - Using an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84% +/- 52.8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45% +/ 35.9). Seventy normal human sera had a mean BI of 10% +/- 9.8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (P less than 0.001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0.68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role of these antibodies as a marker in lupus nephritis is discussed. PMID- 1864006 TI - An abnormal T cell repertoire in hypergammaglobulinaemic primary Sjogren's syndrome. AB - T cell antigen specificity is determined by the products of the genes which encode the variable regions of their receptors. Of the T cell receptor (TCR) variable region gene products examined, only V beta 6.7a TCR-positive lymphocytes were reduced in primary Sjogren's syndrome patients with IgG1 hypergammaglobulinaemia compared with an age-, sex- and HLA-matched control population. The levels of V beta 6.7a T cells were also significantly reduced when these patients were compared with an age- and sex-matched but HLA-unmatched control group and non-tissue typed normal people of both sexes. Since published studies show no such abnormality in rheumatoid arthritis, systemic lupus erythematosus or other autoimmune diseases, this abnormality may reflect a pathogenic process specific to primary Sjogren's syndrome. PMID- 1864007 TI - Anti-IgG antibodies in rheumatic diseases cross-react with Streptococcus mutans SR antigen. AB - We have previously shown that SR protein, a S. mutans major cell wall protein, as well as the recombinant protein SR (rSR) share common epitopes with human IgG. Since this antigenic mimicry could play a role in the induction of anti IgG, we have examined, in k-ELISA, the presence of antibodies reacting with S. mutans SR proteins and S. mutans whole cells in sera from 36 patients with rheumatic diseases. The majority of the 36 sera showed a high reactivity with rSR when compared with control sera. Eight highly positive sera were further purified on rSR and human IgG sorbents and tested against both rSR and IgG in ELISA and Western blotting. The affinity-purified antibodies reacted strongly with rSR, IgG and IgG Fab fragments but failed to react with IgG Fc fragment. In Western blotting the addition of unlabelled IgG abolished the reactivity of affinity purified biotinylated antibodies with all antigens, confirming the existence of a common epitope shared by rSR and human IgG heavy chain. We show the existence in rheumatic diseases of high titres of anti-human IgG antibodies cross-reactive with S. mutans SR proteins. Those antibodies are principally IgG and react with the Fd part of the Fab fragment. We can hypothesize from the above data that this antigenic mimicry existing between S. mutans SR-related antigens and human IgG could play a role in the synthesis of at least a part of the anti-IgG antibodies present in rheumatic diseases sera. PMID- 1864008 TI - Bacterial lipopolysaccharide enhances deposition of immune complexes and exacerbates nephritis in BXSB lupus-prone mice. AB - Systemic autoimmune disease is influenced by genetic, immunological, hormonal, and environmental factors. Although environmental factors are major agents that induce or exacerbate autoimmune diseases, the mechanism(s) and the molecular events by which they operate remain poorly understood. Here we used the lupus prone BXSB mouse as an animal model of systemic autoimmune disease, and we used a bacterial lipopolysaccharide (LPS) as a surrogate infectious agent to gain some insight into the mechanism(s) by which infectious agents exacerbate autoimmune diseases. Our experimental protocol was designed to address three questions: (i) whether spontaneous polyclonal B cell activation (PBA) that occurs in BXSB mice could be further enhanced by bacterial LPS; (ii) whether repeated exposure to LPS would exacerbate autoimmune disease, as reflected by enhanced deposits of immune complexes (ICs) in kidneys and exacerbated nephritis; and (iii) whether the mechanism by which LPS exacerbates nephritis might involve interference with blood cell carrier function, mononuclear phagocyte function, or both. BXSB mice were injected with LPS (25 micrograms) twice a week for 5 weeks; control autoimmune BXSB mice and immunologically normal (C57BL/6) mice were injected with vehicle only. The three groups of mice were then challenged with soluble ICs to assess the kinetics of their disappearance from the circulation, their uptake by the mononuclear phagocyte system (liver, spleen), their distribution in target organ (kidney), and blood cell carrier function. The results indicate that: (i) spontaneous PBA can be enhanced further by LPS; (ii) exposure to LPS results in increased deposits of endogenous ICs in kidneys and exacerbated nephritis; and (iii) defective handling of ICs by the mononuclear phagocyte system and impaired blood cell carrier function are contributory factors to exacerbated nephritis, but that mechanisms in addition to passive localization of ICs may also be operative. PMID- 1864009 TI - Serum levels of soluble IL-2 receptor, IL-4 and IgE-binding factors in childhood allergic diseases. AB - The serum levels of soluble IL-2 receptor (sIL-2R), IL-4 and IgE-binding factors were examined in children with allergic diseases, and compared with those in non allergic controls of the same age and sex. The results showed age-related decreases in the serum levels of sIL-2R and IgE-binding factors, but not in that of IL-4 in both allergic and non-allergic individuals. Significant elevation of sIL-2R was observed in sera from children with atopic eczema or history of an anaphylactic reaction to food, as compared with that in non-allergic controls. The serum concentration of IL-4 was elevated in all allergic groups, including cases of atopic eczema, bronchial asthma and anaphylaxis to food, compared with non-allergic controls, and was correlated significantly with the serum level of IgE (r = 0.59). The IgE-binding factor levels in sera from patients aged 6-10 years with bronchial asthma, or patients aged 1-5 years with a history of food anaphylaxis were elevated as compared with those in non-allergic controls of same age. There was no significant correlation between the serum levels of IgE-binding factors and IgE. Since sIL-2R is released by activated T cells, the present study is in favour of T cell activation causing allergic skin disorders. The serum levels of IL-4 as well as IgE did not differ among allergic patients of different clinical categories. The role of IgE in atopic eczema and other allergic diseases is not clearly established; however, it seems likely that IL-4 is deeply involved in the increased production of IgE seen in allergic individuals. The possible involvement of IgE-binding factors in the age-related changes of clinical manifestations in childhood allergic diseases was also discussed. PMID- 1864010 TI - Soluble IL-2 receptor and CD25 cells in psoriasis: effects of cyclosporin A and PUVA therapy. AB - A study was conducted to quantify soluble IL-2 receptor (sIL-2R) levels in sera of 57 chronic plaque psoriasis patients and correlate these measurements with disease activity and the number of IL-2R-positive (CD25+) lymphocytes in lesional biopsies of 11 cyclosporin A (CsA) and 13 psoralen plus ultraviolet radiation (PUVA) treated patients. Levels of sIL-2R showed a strong correlation with the psoriasis area and severity index (PASI). CsA and PUVA significantly reduced the PASI and sIL-2R levels to a similar degree after 4 weeks of treatment. Although the majority of CsA-treated patients who were biopsied showed reductions in lesional CD25+ cells, these did not reach statistical significance; in five patients biopsied who had PUVA treatment, no consistent effect on the numbers of CD25+ cells was observed. A significant correlation was found between CD25+ cells in lesional biopsies and the PASI score. PMID- 1864011 TI - Increased spontaneous secretion of IL-6 from B cells of patients with B chronic lymphatic leukaemia (B-CLL) and autoimmunity. AB - We studied B cells from 18 patients with B-CLL, six of them with autoimmune haemolytic anaemia, for spontaneous secretion of IL-6. Our aim was to determine whether the increased incidence of autoimmune disease found in B-CLL patients is associated with enhanced spontaneous IL-6 secretion. IL-6 was measured by the effect of B cell supernatants on the proliferation of an IL-6 dependent plasmacytoma cell line T1165. The highest IL-6 values (7.4 +/- 1.8 U/ml) were measured in supernatants derived on day 3 of culture from lymphocytes of the six patients with B-CLL and concomitant autoimmune disease. The maximal IL-6 values for 10 patients with B-CLL only were 2.8 +/- 0.3 U/ml and for 10 age-matched controls, 0.8 +/- 0.3 U/ml (P less than 0.01, each group compared with the other). We conclude that there is an association between B-CLL, autoimmune disease and the spontaneous in vitro secretion of IL-6. Further studies are needed to determine whether the IL-6 secretion plays a role in the pathogenesis of autoimmune disease in patients with B-CLL. PMID- 1864012 TI - Effects of IL-5, granulocyte/macrophage colony-stimulating factor (GM-CSF) and IL 3 on the survival of human blood eosinophils in vitro. AB - The mechanisms that could affect the lifespan of eosinophils after they have left the bone marrow, and their capacity to respond to activation factors were studied by examining the effects of IL-5, GM-CSF and IL-3 on purified human blood eosinophils in culture. All three cytokines prolonged the lifespan of the majority of blood eosinophils. This effect was dose-dependent: IL-5 greater than GM-CSF greater than IL-3. Light density eosinophils from most patients had a longer lifespan in culture than did normal density eosinophils, with or without the three cytokines. Eosinophil death in the absence of these cytokines occurred by apoptosis. Eosinophils from two patients did not survive when cultured with IL 5, although they survived in the presence of IL-3 or GM-CSF. IL-5, GM-CSF and IL 3 induced the expression of the activation epitope on the eosinophil ribonucleases recognized by monoclonal antibody EG2. We conclude that small amounts of IL-5, GM-CSF and IL-3 prevented programmed cell death in human blood eosinophils and induced the expression of the activation forms of eosinophil ribonucleases. We suggest that differences in the capacity of normal and light density eosinophils to survive in culture, and in the ability of eosinophils from some patients to respond to IL-5 could account for variations in the severity of disease seen in patients with persistent eosinophilia. PMID- 1864013 TI - Interleukin-2 receptor gene expression in kidney transplant recipients treated with cyclosporin A. AB - We examined the effects of cyclosporin A (CsA) administered in vivo on the capacity of peripheral blood mononuclear cells (PBMC) from kidney transplant recipients to express IL-2 receptor (IL-2R) gene at the level of mRNA after mitogen stimulation in vitro. There were no differences in the percentage of IL 2R+ cells among the groups of normal individuals, azathioprine-prednisolone treated, and CsA-prednisolone-treated recipients, using FITC-labelled monoclonal anti-IL-2R antibody (anti-alpha chain): 40.3 +/- 10.1% and 62.8 +/- 11.1% of normal PBMC (n = 18), 37.0 +/- 9.3% and 61.7 +/- 5.8% of PBMC from azathioprine prednisolone-treated recipients (n = 20), and 37.7 +/- 9.6% and 60.7 +/- 12.7% of PBMC from CsA-prednisolone-treated recipients (n = 20) expressed IL-2R after 24 h and 48 h of phytohaemagglutinin stimulation, respectively. However, in a study of Northern blotting using cDNA for IL-2R (anti-alpha chain specific), both the 3500 and 1400 bp families of IL-2R mRNA were remarkably decreased in PBMC from CsA prednisolone-treated recipients compared with azathioprine-prednisolone-treated recipients and normal individuals. These studies demonstrated that CsA could inhibit IL-2R gene expression at the level of mRNA at physiological concentration. PMID- 1864014 TI - Ciprofloxacin treatment in vivo increases the ex vivo capacity of lipopolysaccharide-stimulated human monocytes to produce IL-1, IL-6 and tumour necrosis factor-alpha. AB - Because in vitro treatment with quinolones, at pharmacological concentrations, modifies lipopolysaccharide (LPS) induced production of cytokines by monocytes, we studied the effect of orally administered ciprofloxacin (25 mg/kg) on the capacity of peripheral blood monocytes of healthy volunteers to produce tumour necrosis factor-alpha (TNF-alpha), IL-1 activity, IL-1 alpha, IL-1 beta and IL-6 ex vivo in response to endotoxin stimulation. After 7 days of ciprofloxacin, the extracellular and cellular production of TNF-alpha, the cellular production of IL 1 activity, the extracellular and cellular production of IL-1 alpha, and the cellular production of IL-6 increased significantly. Seven days after the end of the treatment, values returned to basal levels or even lower. To our knowledge, this is the first demonstration that ciprofloxacin can modulate in vivo the capacity of human monocytes to react to an inflammatory stimulus such as endotoxin. PMID- 1864016 TI - Natural killer cell tumoricidal activity in cigarette smokers and in silicotics. AB - Cigarette smoking and asbestos exposure have been reported to alter the tumor killing activity of blood natural killer (NK) cells. However, NK cell function in relation to silica dust exposure has not been examined. We studied blood NK cell number, percentage, and tumoricidal activity in 120 hardrock miners, 57 of whom had radiographic evidence of silicosis, and in 33 community controls. There was a significant increase in leukocyte count and lymphocyte count in current smokers compared with former and never smokers, but these cell counts were normal in silicotics and those with silica dust exposure. No significant differences in NK cell (CD16+) number or percentage were found by flow cytometric analysis of smoking or dust exposure groups. Surprisingly, NK tumoricidal activity was significantly higher in cigarette smokers compared with former smokers and never smoker control subjects. Although tumoricidal activity was elevated in silicotics, this was accounted for by their cigarette smoking. These results suggest that cigarette smoking is associated with elevation of blood NK cell tumoricidal activity on a per cell basis, in the absence of any alteration in the absolute number of NK cells in blood. PMID- 1864015 TI - Immunosuppressive effects of 2-acetyl-4-tetrahydroxybutyl imidazole (THI) in the rat. AB - THI is a component of ammonia caramel, a widely used food colouring. The effect of THI on the immune system has been determined in the male F344 rat. THI was given in the drinking water at doses of 1, 10 and 50 mg/l (equivalent to 0.1, 1 and 5 mg/kg per day) to animals on a vitamin B6-deficient diet. After 1 week, the immune competence of the animals was assessed under continued THI treatment. No marked changes in thymus or spleen weight were observed after THI treatment, although there was an increased number of pyknotic cells in the thymic cortex, mainly engulfed by macrophages and there appeared to be a slight thinning of the cortex area. THI produced a significant loss in T and B lymphocytes in peripheral blood but not in the spleen. No change in natural killer (NK) cell activity against YAC-1 target cells was observed in the spleen. The observed increase in NK cell activity in peripheral blood was due to an increase in circulating large granular lymphocytes (LGL). Although the serum antibody titre against keyhole limpet haemocyanin (KLH) was not affected by THI treatment, B cells showed less proliferation when cultured with lipopolysaccharide. T cell function was impeded as measured in mitogen-induced proliferation assay, delayed-type hypersensitivity assay and host versus graft (popliteal lymph node) assay. The results indicate that THI is an immunosuppressor in the rat, in whom it can produce profound lymphopenia and suppression of cell-mediated immunity. PMID- 1864017 TI - Collagen autoantibodies in patients with vasculitis and systemic lupus erythematosus. AB - In order to determine whether collagen autoantibodies are present in sera from patients with vascular diseases, a highly sensitive solid-phase radioimmunoassay was utilized to evaluate the presence of antibodies against collagen types I to VI and laminin in sera of 20 patients with vasculitis and 20 patients with systemic lupus erythematosus (SLE). Autoantibodies to interstitial collagen types I and II were noted in 20 and 35% of the patients, respectively. Most significantly, 70% of the polyarteritis nodosa patients and 55% of the total vasculitis group had autoantibodies to collagen type IV. In SLE, autoantibodies to collagen type V were detected in 70% and to collagen type IV in 85% of the patient sera. These data indicate that basement membrane and basement membrane associated collagens may become immunogenic in patients with vasculitis and SLE. The role of these autoantibodies is most likely a result of endothelial damage secondary to the initial inflammatory disease process. However, it can be concluded from the present studies that collagen types IV and V are involved in the immune response and thereby may perpetuate further vascular damage. PMID- 1864018 TI - Stressor-induced changes in mitogenic activity are not associated with decreased interleukin 2 production or changes in lymphocyte subsets. AB - Splenic lymphocytes from Lewis rats that received presentations of physically aversive electric shock demonstrated a marked reduction in responsiveness to T cell mitogens such as concanavalin A. This study examined cellular mechanisms which may be responsible for this functional alteration. There was no difference in distribution of T-cell subsets from shocked and nonshocked rats. There was no difference in the production of interleukin 2 (IL-2) nor was there a difference in the percentage of IL-2 receptor positive T cells or T-cell subsets after culture for 24 hr. However, there was a marked lack of mitogenic stimulation in splenocytes from shocked rats when stimulated with the calcium ionophore A23187. This indicates a defect in the biochemical pathways necessary to activate T-cell mitogenesis. PMID- 1864019 TI - Mesenchymal specificity of three new monoclonal antibodies generated to the osteosarcoma cell line 4444T. AB - We have generated three murine monoclonal antibodies to the new human osteosarcoma cell line 4444T. Analysis of their binding patterns to tumor cell lines, normal human tissues, and surgical tumor specimens indicates that the antibodies recognize a subset of human sarcomas and stromal tissues but fail to react with carcinomas or normal human epithelial tissue. These mesenchyme specific monoclonal antibodies bind to antigens in the extracellular matrix. One antibody is specific in its binding to the muscularis arteriosus. We expect these antibodies to aid in the identification of sarcomas and to extend our knowledge of the components of the extracellular matrix and its interaction with tumors. PMID- 1864020 TI - Membranoproliferative glomerulonephritis in dogs with a genetically determined deficiency of the third component of complement. AB - Renal disease is a common clinical manifestation of genetically determined deficiencies of the complement system in man. Like their human counterparts, dogs with a genetically determined complete deficiency of C3 also develop renal disease. Five of 20 C3-deficient dogs developed clinical evidence of renal failure. However, 14 of the 15 remaining dogs had histological evidence of type I membranoproliferative glomerulonephritis. The lesions were characterized by mesangial cell proliferation, an increase in the mesangial matrix, thickening of the glomerular capillary wall, electron-dense deposits in the mesangium and subendothelial space, and the presence of IgG and IgM. In order to determine the effect of treatment with C3 on the renal disease of C3-deficient dogs, two C3 deficient dogs were infused with normal canine plasma twice weekly for 3 weeks. Their urinary protein excretion rose progressively from less than 200 mg/24 hr to greater than 1000 mg/24 hr; renal function remained normal. Renal biopsies performed 1 week after the last infusion revealed more severe glomerulonephritis and the presence of C3. As controls, a C3-deficient dog was given C3-deficient canine plasma and a normal dog was given normal canine plasma; neither control animal developed proteinuria or changes in their renal biopsy. These observations suggest that renal disease may be more common in humans with complement deficiencies than would be suspected based on clinical assessment. Furthermore, these results suggest that treatment with complement-containing blood products may worsen preexisting renal disease in complement-deficient individuals. PMID- 1864022 TI - Inductive logic expert system shell in dental diagnosis. PMID- 1864021 TI - A simplified technique for root resection in maxillary molars. PMID- 1864023 TI - Non-surgical periodontal treatment. PMID- 1864025 TI - Total arthroplasty and the Veterans Administration. PMID- 1864024 TI - Osteosarcoma of the mandible--early signs and symptoms--case report. PMID- 1864026 TI - Postoperative urinary retention associated with total hip and total knee arthroplasties. AB - Urinary retention following total hip and knee arthroplasty is a common problem frequently necessitating either prolonged urethral catheter drainage or intermittent catheterization. The direct relationship of urinary tract instrumentations, procedures, and infections to deep sepsis in total hip replacements is well documented. Pharmacologic therapy to stimulate voiding or augment bladder emptying is thus theoretically preferable to the use of catheterization. Prasozin hydrochloride, an alpha blocker, relaxes the smooth musculature of the posterior urethra and prostrate and has been used to treat urinary obstruction secondary to benign prostatic hypertrophy. A prospective study in 60 male patients showed a statistically significant decrease in postoperative urinary retention with the perioperative administration of prazosin (p less than 0.01). A higher incidence of urinary tract infection was seen in patients who developed urinary retention (3% versus 20%) (p less than 0.01). Uroflowmetry parameters were not predictive of the patient at risk for retention and were unaltered with the administration of prazosin. Prazosin can be an effective adjunct in the prophylaxis of postoperative urinary tract infections and may decrease the potential risk for total joint sepsis. PMID- 1864027 TI - Prevention of thromboembolic disease following total knee arthroplasty. Epidural versus general anesthesia. AB - Seventy-two patients were randomized into a prospective clinical trial to evaluate the effects of epidural (EA) versus general anesthesia (GA) on the incidence of thromboembolic disease (TED) following total knee arthroplasty (TKA). Males received aspirin 650 mg po bid and females low-dose warfarin daily to maintain the prothrombin time at 15 to 16 seconds for pharmacologic prophylaxis against TED. Thirty-four patients had EA and 38 GA for their primary TKA. Contrast venography and ventilation-perfusion scanning were performed on the sixth, seventh, and eighth postoperative days, and these were interpreted in a blinded fashion. The mean age of the 45 males and 27 females was 64 years (range, 42-84 years). There were no significant differences between the two groups with respect to hematocrit, operative time, blood loss, number of units transfused, or hospital stay. Twelve of the 34 patients (35%) receiving an EA and 10 of the 38 patients (26%) receiving GA developed TED, an overall incidence of 31% (p greater than 0.05) Fifty-three percent of the clots were located in the popliteal vein above the trifurcation or more proximal. However, the incidence of proximal vein thrombosis was significantly less in patients receiving an EA (46%) rather than a GA (64%). The incidence and distribution of clots was not affected by the type of pharmacologic prophylaxis, gender, or use of methylmethacrylate. Ten percent of the patients had a positive scan by strict criteria and were thought to have a pulmonary embolism (PE). In patients with a femoral vein clot, the incidence of PE was 67%. One bleeding complication occurred in a patient who took double the appropriate warfarin dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864028 TI - The use of periosteally vascularized autografts to augment the fixation of large segmental allografts. AB - Large segmental bone grafts are a standard of reconstructing long bone defects. Nonunion or delayed union at the host-graft junction is a major complication of these procedures. In six patients, a nonunion was treated by locally available bone, vascularized by its periosteum as an onlay autograft to improve fixation and speed incorporation of the allograft into the host bone. At three months, all were pain free and using their allografts without limitation. By four months, all had roentgenographic evidence of allograft and autograft incorporation. During the follow-up period from two to four years, all have incorporated the allografts and are pain free. PMID- 1864029 TI - Investigation of early surface delamination observed in retrieved heat-pressed tibial inserts. AB - The objective was to examine possible reasons for delamination observed in tibial inserts of the porous-coated anatomic (PCA) knee replacement. To date, 33 PCA inserts have been forwarded to the authors' labs. Of these 33, 52% showed severe delamination within four years of implantation. Visual, structural, and mechanical analyses were conducted and data compared on the heat-pressed PCA type and the common machined inserts. Twenty inserts of the two different types were examined. Visual data using polarized light microscopy showed the presence of a surface layer separated from the middle region of the heat-pressed inserts by a line of demarcation 250-580 microns beneath the articulating surface. This anomaly was not observed in machined inserts. Structural analysis showed the new heat-pressed inserts had increased crystallinity in the surface layer when compared to new machined inserts. The retrieved heat-pressed inserts showed increased crystallinity in the surface and middle regions. There was a slight increase in surface crystallinity in the retrieved machined inserts. Microhardness data showed that there was an increased hardness associated with the crystallinity seen on the heat-pressed inserts. Orthopedic surgeons should be aware of early delamination and surface failure in heat-pressed inserts. PMID- 1864030 TI - Fuller Albright. His concept of postmenopausal osteoporosis and what came of it. AB - Fifty years ago Albright contributed the following to understanding osteoporosis: (1) He recognized it as a deficiency of formation, not of mineralization of bone matrix; (2) he observed that 40 of 42 patients with osteoporosis before age 65 were women past menopause or young women postoophorectomy; (3) he concluded that estrogen stimulates osteoblasts (a conclusion later challenged); (4) he demonstrated by metabolic balance studies that estrogen causes a positive calcium balance in postmenopausal osteoporosis; (5) he introduced periodic progesterone to prevent or treat endometrial hyperplasia from prolonged estrogen therapy; and (6) he showed that long-term therapy arrested vertebral damage and height loss in postmenopausal osteoporosis and prevented them if started early. Since Albright's time, more sensitive methods of assessing bone density have replaced conventional roentgenograms. Some large scale trials of estrogen have indicated increased bone density and fewer fractures. Unopposed estrogen increases risk of endometrial cancer and decreases mortality from other cancers, myocardial infarction, stroke, and osteoporosis. Trials of calcitonin, diphosphonates, fluoride, vitamin D, and high calcium intake have not proved more effective than estrogen. PMID- 1864031 TI - Pyogenic vertebral osteomyelitis with paralysis. Prognosis and treatment. AB - In the interval between 1983 and 1988, 14 patients were treated for pyogenic spondylitis complicated by neurologic compromise. There were nine males and five females aged 39-80 years. The average time between onset of symptoms and diagnosis was 2.8 months. Predisposing factors were diabetes mellitus in four patients and urinary tract infections in five patients. The infection was blood borne in all 14 patients. In two patients, the infection was superimposed on a recent vertebral fracture. The cervical spine was involved in one patient; the thoracic spine in seven; and the lumbar spine in six patients. Six patients presented with a Frankel B paralysis, six with a Frankel C paralysis, and two with grade D paralysis. The neurologic symptoms lasted between one day and six weeks before surgery. Twelve patients had anterolateral decompression. Two of the 12 patients had a second stage posterior stabilization. Two patients were deemed inoperable. All surviving patients were managed by parenteral antibiotics for three to six weeks followed by enteral route for a total of three to six months. All 12 operated patients had a significant neurologic improvement (one grade or more on the Frankel scale) with solid interbody fusion. PMID- 1864032 TI - Chemonucleolysis in the herniated L3-L4 disk. AB - In a continuous series of 770 patients with a herniated disk treated by chemonucleolysis, 16 patients had herniation of the L3-L4 disk (2.1%). There were no complications, and none of these 16 patients had open surgery after the initial treatment. A follow-up study was performed after 39 months (range, six to 80 months) in 15 patients. Three patients were for the most part satisfied and 12 patients were fully satisfied with the result of treatment. Residual pain was minor in most patients. Roentgenographic signs of increased disk degeneration were seen in six patients, and reexpansion of the disk to some degree was noted in four patients. Chemonucleolysis is effective for treatment of the herniated L3 L4 disk. PMID- 1864033 TI - Sublaminar fixation in lumbosacral fusions. AB - Sublaminar fixation to stainless steel rectangles was employed in an effort to improve the fusion rate in lumbar and lumbosacral arthrodesis. Thirty-seven patients had spondylolisthesis, and 26 had other causes of pain secondary to lumbar mechanical instability. Of the 63 patients, 53 achieved fusion and 52 had relief of pain. No infections or neurologic complications were encountered. This fusion rate of 84% does not significantly differ from rates obtained with noninstrumented methods, and this construct is no longer used for lumbar fusions. PMID- 1864034 TI - Noncemented porous-coated anatomic total hip arthroplasty. AB - In 1984, as an alternate to the acrylic fixation of the components of total hip arthroplasty, the use of an uncemented porous-coated anatomic (PCA) hip system with a beaded porous coating to achieve biologic fixation was initiated. Since then, 44 patients with cementless acetabular components and 35 patients with cementless femoral components have been followed for a minimum of 24 months and an average of 37 months. Harris hip scores averaged 90.5 at most recent follow-up intervals. No reoperations were necessary for failures of fixation or change in position of the acetabular component. Ominous roentgenographic signs such as progressive bead shedding, progressive radiolucencies, or progressive component migration have not occurred. Two femoral component revisions have been necessary: one for intractable pain and one for pain and roentgenographic loosening. Although thigh pain has been prevalent (20%), all patients have been accommodated and have retained stable hip scores. Progressive radiolucencies and progressive implant subsidence have been rare occurrences. The authors continue to use the cementless acetabular component in all cases of total hip arthroplasty in which initial stability can be obtained. It is their preference to cement the femoral component in patients over 65 or when initial stability cannot be achieved. PMID- 1864035 TI - Shoulder impingement syndrome. A critical review. AB - Impingement syndrome is an ill-defined term for a variety of disorders of the shoulder that manifest as anterior shoulder pain, especially during overhead activities. These disorders each have a common pathologic course that includes rotator cuff tendinitis (RCT), and, if untreated, may proceed to cuff rupture. RCT has at least two distinct etiologies. Primary impingement of the supraspinatus tendon on the coracoacromial arch is responsible in the majority of nonathletic cases. Overhead movements in sports are prone to developing secondary mechanical impingement because of an instability pattern that is common in this population. Information from this review and clinical practice permits differentiation of the two distinct etiologies of RCT which is important in treatment planning. Much work still needs to be done in defining the microscopic pathology of RCT. PMID- 1864036 TI - Scapular fractures. Analysis of 113 cases. AB - Scapular fractures have been the subject of study since Desault's treatise of 1805, but few large-scale studies have been completed with long-term follow-up evaluation of displaced scapular neck and spine fractures. This series of 148 fractures in 116 scapulae (113 patients) appears to be the largest ever reported and the only one with a follow-up study of a significant group (24 patients). Significant disability was found in patients with displaced scapular spine and neck fractures: (1) pain at rest in 50%-100%, (2) weakness with exertion in 40% 60%, and (3) pain with exertion in 20%-66%. Based on these findings, the indications for operative management should be expanded to include displaced scapular neck and spine fractures. Using extensile exposure through a posterior Judet incision, rigid internal fixation, and early motion, results in eight cases were excellent. All patients recovered at least 85 degrees of glenohumeral abduction, normal scapulothoracic motion, and none had resting pain, night pain, or pain with abduction. The minimum follow-up study period was 15 months. PMID- 1864037 TI - Differences in shoulder muscle activity between patients with generalized joint laxity and normal controls. AB - The aim of the present study was to analyze shoulder muscle activity in patients with generalized joint laxity and shoulder instability and to compare it with muscle activity recorded in healthy subjects from an earlier study. Electromyographic (EMG) activity was recorded from eight shoulder muscles in six patients using surface and intramuscular fine-wire electrodes. Recordings were made from the subscapularis, supraspinatus, infraspinatus, pectoralis major (sternoclavicular part), the anterior, middle, and posterior parts of the deltoid, and the latissimus dorsi. The EMG signal was low-pass filtered, full wave rectified, and time-average. Normalization of the EMG allowed interindividual and intraindividual comparisons. During abduction and flexion, muscle activity in the anterior and middle parts of the deltoid was significantly decreased in the patients, and during internal rotation activity in the subscapularis was increased. As in healthy subjects, patients showed simultaneous activity in both those muscles producing the movement and in the antagonistic muscles. The altered muscle activity observed in patients with generalized joint laxity provides (1) a basis for understanding the mechanism of their shoulder instability and (2) the rationale for a physical training program for these patients. PMID- 1864038 TI - The failed ulnar nerve transposition. Etiology and treatment. AB - Various procedures have been recommended for the treatment of cubital tunnel syndrome. Simple decompression in situ, medial epicondylectomy, subcutaneous transposition, intramuscular transposition, and submuscular transposition all have their advocates. The results of the surgical treatment for cubital tunnel syndrome are related to the severity of the compressive neuropathy at the time of diagnosis and to the adequate decompression of the nerve at all sites of potential compression at the time of surgical treatment. Fourteen patients who had previously undergone surgical treatment for cubital tunnel syndrome were evaluated because of persistent pain, paresthesia, numbness, and motor weakness. All patients had documented persistent compression of the ulnar nerve on clinical and electromyographic evaluation. The indication for repeat surgical exploration in all patients was unremitting pain despite nonoperative treatment. All patients had been treated by neurolysis and submuscular transposition of the ulnar nerve as described by Learmonth. The causes of continued pain after initial surgery included retention of the medial intermuscular septum, dense perineural fibrosis of the nerve after intramuscular and subcutaneous transposition, adhesions of the nerve to the medial epicondylectomy site, and recurrent subluxation of the nerve over the medial epicondyle after subcutaneous transposition. Revision surgery was found to be highly successful for relief of pain and paresthesias; however, the recovery of motor function and return of sensibility were variable and unpredictable. PMID- 1864039 TI - Posterior dislocation of the elbow. AB - Posterior dislocation of the elbow is associated with significant morbidity and incomplete recovery. In this series of 32 patients, those with associated fractures, posterolateral dislocations, delayed reduction, and rigid immobilization had the least satisfactory outcome. PMID- 1864040 TI - Prospective study of porous-coated anatomic total hip arthroplasty. AB - Seventy-five uncemented porous-coated total hip prostheses were implanted in 64 patients. The results were reviewed after a mean follow-up period of 47 months (range, 40-64 months). The mean preoperative rating was fair, and the mean postoperative rating was excellent. There were six dislocations. Ten patients had mild thigh pain at one year; by two years, the pain had resolved in six patients. Neither moderate nor severe limp nor significant loosening of beads was observed. Only one patient had progressive radiolucent lines. The high rate of dislocation may be related to a compromise of acetabular position to obtain bony fixation in acetabula early in the series. The clinical results were encouraging. PMID- 1864041 TI - The noncemented porous-coated hip prosthesis. A three-year clinical follow-up study and roentgenographic analysis. AB - This was a retrospective study reviewing 68 hip arthroplasties performed with noncemented, porous-coated components at three institutions in the period between December 1983 and June 1987. Fifty of these were available for follow-up study. The mean follow-up period was three years (range, 18-56 months). Thirty-seven patients were treated by total hip arthroplasty (THA) with porous-coated components, and thirteen were implanted with porous-coated femoral stems with bipolar endoprostheses using a porous-coated femoral stem and a universal head. The mean Harris hip score at follow-up evaluation for the entire group was 85.7 points. Eighty percent of the patients had either a good or excellent result. Those patients implanted with a porous femoral stem with bipolar acetabular components had only 54% good or excellent results compared with 90% good or excellent results for those having THA. Roentgenographic findings included a 59% rate of femoral neck cortex osteopenia, an 80% rate of medial or lateral distal cortical hypertrophy, and an 80% rate of distal bone bridging. All of these roentgenographic changes were secondary to changes in stress transference to the proximal femur. There was no correlation between thigh pain or the degree of bone prosthesis radiolucencies and the fit of the femoral stem. PMID- 1864042 TI - In vivo measurements of relative motion between an uncemented femoral total hip component and the femur by roentgen stereophotogrammetric analysis. AB - Roentgen stereophotogrammetric analysis (RSA) was used to study rotation and subsidence of an uncemented polyethylene-coated femoral component for total hip arthroplasty in ten patients younger than 55 years of age. Three years postoperatively, the total subsidence averaged 2.44 mm and the internal rotation was 7.4 degrees. The rate of subsidence decreased between the observation periods, whereas the rate of rotation, after an initial significant decrease, became almost constant. One patient, who was a clinical failure and required revision arthroplasty, had a significantly higher rate of migration after six months. The pattern of subsidence in the absence of pain might be the normal reaction of bone to an uncemented prosthesis, but the continuing rotation suggests the potential for failure of the arthroplasty. The type of analysis made possible in RSA may allow early prediction of the success of arthroplasties and significantly speed the design cycle for arthroplasty components. PMID- 1864043 TI - Sexual function after total hip arthroplasty. AB - Eighty-six patients who had successful total hip replacement completed questionnaires on their sexual activity. Preoperatively, 46% of patients attributed significant sexual difficulties to their hip disease, whereas only 1% felt that their hips remained a significant source of problems postsurgery. The majority (55%) of patients were able to resume intercourse one to two months postoperation. Male patients were statistically more likely to resume intercourse sooner than their female counterparts. Patients were also questioned about which coital positions they found comfortable after arthroplasty. The supine position (patient on bottom) was the most preferred. The next most comfortable position for males was prone (patient on top), yet for female it was sidelying on the nonoperative hip. In addition, 89% of patients desired more information regarding sexual function postarthroplasty, preferably in the form of a booklet. Therefore, a booklet was written specifically for postoperative patients and their sexual partners. PMID- 1864044 TI - Sesamoid disorders and treatment. An update. AB - The anatomy, function, and disorders of the hallucal sesamoids show that the diagnosis and current concept of management are based on the individual patient's problems. The treatment should always be initiated in a conservative fashion, generally using a molded insole with an appropriate excavation to shift weight from a painful sesamoid. The advantages and disadvantages of sesamoidectomy are influenced by surgical technique. Care in handling the medial and lateral hallucal nerves is essential. Removal of both the medial and lateral sesamoids invariably leads to an intractable clawtoe deformity and is absolutely contraindicated. PMID- 1864045 TI - Compartment syndrome of the foot after intraarticular calcaneal fracture. AB - Seventeen patients with a total of 21 intraarticular calcaneal fractures were examined at up to 30 days after trauma for the development of tissue pressure in the central plantar muscle compartment. Twelve patients had a significant increase in tissue pressure with values greater than 30 mmHg because of primary fracture hematoma or interstitial fluid accumulation. This increase in pressure persisted for three to five days after trauma, so that ischemic damage to the short plantar foot muscles had to be suspected. Plantar muscle scarring and claw toe formation were observed in seven patients with a total of 11 fractures during a mean observation period of 18 months. The plantar aponeurosis, which forms the constricting fascial envelope of the plantar muscles, is the anatomic structure responsible for the compartment syndrome that may develop after calcaneal fracture. Therefore, to avoid functional deficit, plantar compartmental pressures should be regularly measured after calcaneal fracture. Significantly increased plantar tissue pressure greater than 30 mmHg should be relieved by longitudinal incision of the plantar aponeurosis, preferably by a plantar incision as soon as the diagnosis is made. PMID- 1864046 TI - Symptomatic talocalcaneal coalition. Its clinical significance and treatment. AB - The clinical significance of symptomatic talocalcaneal coalition was described subjectively, objectively, and identified roentgenographically after examining 67 feet of 42 patients between 1977 and 1987. Computed tomographic examinations, conducted on 29 of 42 patients, were useful in recognizing the extent of coalition, the condition of union, and the postoperative results. Tarsal tunnel syndrome was present in 23 feet with the coalition. Thirty-one feet (24 patients) were treated conservatively and 36 feet (29 patients) surgically. Of the surgically treated feet, the coalition was excised in 33 and talocalcaneal fusion was performed in three. Follow-up examinations were performed at an average of 5.3 years (range, 2.25-11.2 years). In the excision group, the results were excellent in 24 feet, good in seven, and fair in two. The results were good in three feet treated by arthrodesis. PMID- 1864047 TI - Patient activity, sports participation, and impact loading on the durability of cemented total hip replacements. AB - Patients with either cemented surface replacements or cemented stemmed hip prostheses and who regularly participate in sporting activities or heavy labor after total joint arthroplasty are at twice the long-term risk of requiring revision surgery for loosening as patients who are less active. For patients with surface replacement total hip arthroplasty (THA), the adverse effects of activity are greatest in patients with preoperative diagnoses other than osteoarthritis, and were seen by the sixth year postsurgery. For patients with conventional stemmed prostheses, the effects of patient activity are not seen until about ten years postsurgery. For resurfacing THA for osteoarthritis, the long-term of loosening is primarily in patients who participate in high impact activities. PMID- 1864048 TI - Ultrastructure, tartrate-resistant acid phosphatase activity and calcitonin responsiveness of osteoclasts at sites of demineralized bone matrix implant induced osteogenesis. AB - The morphology, ultrastructure, tartrate-resistance acid phosphatase reactivity, and calcitonin responsiveness of osteoclasts induced at sites of demineralized bone matrix (DBM) implant-induced osteogenesis in rats were determined. Osteoclasts at these ectopic sites had a morphologic and ultrastructural appearance similar to osteoclasts normally found in skeletal tissues. When observed by scanning electron microscopy, resorption surfaces on the implants had well-defined resorption pits (Howship's lacunae), indicative of active bone resorption. The osteoclasts stained intensely for tartrate-resistance acid phosphatase, an enzyme that is specific for osteoclasts. In response to human calcitonin, hypocalcemia occurred and osteoclasts lost their ruffled borders, indicating that these cells are responsive to exogenous hormonal stimulation. The osteoclasts induced by subcutaneous implantation of DBM had morphologic and functional characteristics similar to osteoclasts normally found in skeletal tissues. PMID- 1864049 TI - Effect of immunosuppression on rejection of cartilage formed by transplanted allogeneic rib chondrocytes in mice. AB - The effect of short-term immunosuppressive treatment with antithymocyte serum procarbazine (ATS-PCH) and cyclosporin-A (Cy-A) on survival of allogeneic rib chondrocyte grafts was examined morphologically and by evaluation of specific humoral and cellular antigraft immunity. The latter were evaluated by means of leukoagglutination and the indirect migration inhibition assay, respectively. Untreated recipients of syngeneic rib chondrocytes and untreated recipients of whole syngeneic and allogeneic rib cartilage served as controls. Transplanted syngenic rib chondrocytes formed cartilaginous nodules similar to rib cartilage in situ. These nodules contained hypertrophied chondrocytes, but neither physiologic resorption by vascularized connective tissue nor bone formation occurred after an observation period of longer than six weeks. Transplantation of allogeneic chondrocytes resulted in development of humoral and cellular antigraft immunity, and the formed cartilage was destroyed by infiltrating immune cells. Immunosuppression by ATS-PCH resulted in inhibition of graft destruction and a marked decrease of specific humoral antigraft immunity. Cellular antigraft immunity did not occur. Moreover, neither the histologic appearance of the cartilaginous nodules nor the results of immunologic response evaluations in the ATS-PCH-treated group differed from those in untreated whole allogeneic cartilage recipients. Treatment with Cy-A did not significantly improve survival cartilage formed by allogeneic chondrocytes. PMID- 1864050 TI - Bone induction in nonhuman primates. An experimental study on the baboon. AB - Development leading to local bone differentiation in response to intramuscular and subcutaneous implantation of demineralized bone matrix has been predominantly investigated in rodents. To investigate bone differentiation by induction in primates, diaphyseal bone was harvested from ten male baboons and chemosterilized to obtain autolyzed, antigen-extracted allogeneic (AAA) bone containing the bone morphogenetic protein essential for osteoinduction. A total of 96 AAA bone diaphyseal cylinders were implanted intramuscularly in 24 adult male baboons and harvested at three, six, and nine months. Histologic analysis showed that the matrix had undergone considerable resorption, particularly at six and nine months. Seventy-three implants showed variable amounts of newly formed bone at the internal and external surfaces of the chemosterilized matrix. Numerous specimens showed florid bone formation, and newly formed woven bone persisted in association with the matrix for as long as nine months. Coating the AAA bone matrix with an allogeneic fibrin-fibronectin protein concentrate prepared from fresh-frozen baboon plasma did not significantly increase the amount of induced bone. Bone formation was confirmed by intravital double tetracycline labeling of the mineralization fronts. The unequivocal demonstration of bone formation by induction in a large series of adult nonhuman primates provides evidence that long-lived higher vertebrates retain the bone-inductive proteins in the extracellular matrix of bone and the crucial set of responding mesenchymal cells capable of transformation and differentiation into osteoblastic cell lines. PMID- 1864051 TI - Anterior cruciate ligament allograft transplantation in dogs. AB - The biomechanical and clinical performance of bone-ligament-bone anterior cruciate ligament (ACL) allografts was studied in eight dogs. Allografts were collected from skeletally mature, healthy dogs using aseptic technique, and stored at -70 degrees for three to five weeks before implantation. The allografts were size-matched to the recipient dogs using ACL length and then rigidly fixed in position with interference screws and Kirschner wires. Three dogs regained a normal gait, and their grafts sustained breaking loads that were 25%, 41%, and 59% of controls. Partial or complete graft failure occurred in the other five dogs at some point in the study. Four had intraligamentous rupture and one had an avulsion fracture of the femoral attachment site. Joint-fluid cytology was normal in all eight dogs. Histologic examination showed persistent lymphoplasmacytic infiltrate. Eventually the allograft cores were incorporated in the host bed. Hyperplasia and fibrosis of the synovial membrane were diffuse and persisted as focal accumulations of mononuclear inflammatory cells. PMID- 1864052 TI - Total hip arthroplasty following failed internal fixation of hip fractures. AB - A retrospective review was performed on 27 consecutive patients with total hip arthroplasty (THA) following failure of internal fixation of fractures of the proximal femur. The results were comparable to primary THA in femoral neck fractures. Considerably less satisfactory results were obtained in THA in intertrochanteric fractures. Bone loss and medial displacement of the femoral shaft led to high incidence of intraoperative complications and postoperative dislocations. Extreme care must be taken to avoid fracture and penetration of the femoral shaft. Autograft, allograft, or head and neck replacement components should be available for reconstruction of the difficult cases. PMID- 1864053 TI - Triphasic bone scanning following porous-coated hip arthroplasty. AB - In a long-term follow-up evaluation of a homogenous group of patients with a standardized total hip arthroplasty for coxarthrosis, the imaging levels follow a predictable pattern over a prolonged period of time. Because of the prolonged nature of increased uptake in the static phases, the utilization of bone scanning in the early diagnosis and evaluation of the patient with a painful noncemented hip may have little value. Increased blood pool and blood flow studies may indicate localized pathology, but, at the present time, static images of noncemented hip arthroplasty within 12 months of surgery probably are of little diagnostic value. PMID- 1864054 TI - Recurrent dislocation of the shoulder. 1943. PMID- 1864055 TI - Uncemented total hip arthroplasty. Prospective analysis of the tri-lock femoral component. AB - Fifty consecutive hip disease patients (56 hips) with total hip arthroplasties (THA) utilized the uncemented Tri-Lock femoral component. Forty-five patients (51 hips) were followed for an average of 46 months (range, 24-66). Forty-two patients (47 hips) were followed with clinical examination and roentgenographs, three (four hips) by telephone interview, four (four hips) were deceased, and one (one hip) was lost to follow-up evaluation. The diagnoses included osteoarthritis (30 hips), avascular necrosis (11 hips), juvenile rheumatoid arthritis (two hips), and degenerative joint disease secondary to childhood hip disorder (four hips). Of 47 hips, 34 were graded excellent, seven good, three fair, and three poor using the Harris hip score. The incidence of thigh pain was 19% at one year, but only 6% at final follow-up evaluation. Limp persisted in 19% of the patients. Of the three patients with four hips contacted by telephone, two had slight pain and two had no pain. The roentgenographic results found an alarming 38% incidence of varus shift of the components, relative to their preoperative position. The presence of a varus shift did not adversely affect the clinical results. Early experience with the Tri-Lock femoral component shows results comparable to those reported in the literature. The high incidence of femoral component shift, presumably because of geometry of the stem is of concern. Longer follow-up evaluation will be necessary to determine the fate of these uncemented THA operations. PMID- 1864056 TI - Total knee arthroplasty at a Veterans Administration Medical Center. AB - Total knee arthroplasty (TKA) was evaluated in 256 consecutive knees in a Veterans Administration hospital. Patient satisfaction and the effect of intercurrent illness were studied in addition to standard clinical and roentgenographic parameters. Evaluation of results show the superiority of condylar knee designs. In general, TKA was successful with a high degree of patient satisfaction. PMID- 1864057 TI - Results of total knee arthroplasty using the posterior stabilized condylar prosthesis. A report of 137 consecutive cases. AB - One hundred thirty-seven consecutive posterior stabilized total knee arthroplasties (TKAs) were reviewed. Average age of the patient was 61.1 years and length of postoperative follow-up period was 29.2 months. Patients were evaluated using the Hospital for Special Surgery (HSS) knee rating scores. Average preoperative scores improved from 52 to 92, postoperatively. Ninety-eight percent of patients had no pain or mild occasional pain postoperatively compared with 99% of patients experiencing severe to disabling pain preoperatively. Complications included one myocardial infarction, two deep venous thrombosis, one urinary tract infection, one patellar dislocation, and four wound problems. There were two incidences of seroma, one hematoma, and one deep infection requiring revision after joint debridement and systemic antibiotics. Also noted was one incidence of ligamentous laxity and one patella fracture. PMID- 1864058 TI - Effect of the tibial cut on subsidence following total knee arthroplasty. AB - In 33 total knee arthroplasties (TKAs) using instrumentation designed to cut the tibia with 0 degree posterior slope, ten tibial components demonstrated at least 2 mm of tibial component subsidence. These subsided components were implanted onto tibiae with an average of 8 degrees +/- 2 degrees difference between the preoperative, anatomic posterior slope and their postoperative posterior slope. The remaining 23 components, without subsidence, were implanted onto tibiae cut within 2 degrees +/- 2 degrees of their anatomic slope. To help understand these clinical observations, a laboratory study was performed to compare the load carrying capacity and the stiffness of tibial subchondral bone following two types of tibial cuts: one made perpendicular to the long axis of the tibia and the other made parallel to the articular surface of the tibia. Mock tibial baseplates mounted on paired cadaver tibiae were loaded in compression and force displacement curves were recorded. Tibiae cut parallel to the surface exhibited 40% greater load carrying capacity and 70% greater stiffness than the paired tibiae cut perpendicular to the long axis. The biomechanical data of this study indicated that cutting the tibia perpendicular to the long axis results in weaker bone that may be inadequate to support a tibial component. This may explain the higher incidence of clinical subsidence if the tibial cut is not made approximately parallel to the anatomic slope. PMID- 1864059 TI - Subvastus (Southern) approach for primary total knee arthroplasty. AB - The subvastus or Southern approach to the knee had been described as early as 1929 but is not found in standard modern orthopedic textbooks. This approach for primary total knee arthroplasty (TKA) preserves the integrity of the extensor mechanism and maintains the vascular supply to the patella. To appreciate the potential benefits of this approach, a complete understanding of the surgical anatomy is essential. The benefits of the subvastus approach make it a valuable technique for primary TKA. PMID- 1864060 TI - Total knee arthroplasty. Two- to four-year experience using an asymmetric tibial tray and a deep trochlear-grooved femoral component. AB - The design features of an implant system can be crucial to the success of cementless total knee arthroplasty (TKA). The implant system described in this study incorporates anatomic features including an asymmetric tibial tray that is smaller laterally than medially, and a deep trochlear-grooved femoral component. Two hundred consecutive primary total knees were implanted between October 18, 1985 and January 19, 1988 and were followed prospectively. One hundred ninety-two were implanted without cement. Clinical evaluation demonstrates good or excellent results in 96%, including a mean range of motion of 122 at two to four years after arthroplasty. Routine fluoroscopic spot roentgenograms have shown no complete radiolucency in this series of patients. Bone ingrowth was predictable if morselized autograft bone was interposed between implant and host bone. Implant retrievals demonstrated uniform bone ingrowth into the porous coating, increasing to 40% of the pore volume in the tibial tray at 27 months. Restoration of the normal kinematics appears to minimize the bone-implant stress permitting bone ingrowth fixation. The results of primary cementless TKA in this series is comparable to cemented TKA with the advantage of conserving bone stock. PMID- 1864061 TI - Intermittent pneumatic compression versus coumadin. Prevention of deep vein thrombosis in lower-extremity total joint arthroplasty. AB - One hundred forty-nine consecutive patients requiring lower extremity total joint arthroplasty were randomized to either coumadin (52 patients) or intermittent pneumatic compression (48 patients) as prophylaxis against deep vein thrombosis (DVT). Forty-nine patients were excluded. When fully ambulatory, the presence or absence of DVT was diagnosed by ascending venography (90% of patients), nuclear venography, venous dopplers, or impedence plethysmography. The two groups were similar in average age (64 years), indication for arthroplasty (pain because of arthritis in 90%), gender (98% male), and average number of risk factors (2.4). Twenty-five percent of patients on coumadin and 25% of patients on intermittent pneumatic compression (IPC) developed DVT. IPC was more effective than coumadin following primary total hip arthroplasties (THAs) (16% versus 24% incidence DVT); coumadin was more effective than IPC following primary total knee arthroplasties (TKAs) (19% versus 32% incidence of DVT). DVT developed in 36% of patients following revision arthroplasty. Seventy-five percent of all thrombi were proximal. Both IPC and coumadin were found to be safe; there was no increased perioperative bleeding in the coumadin group. Of three postoperative deaths, one was possibly due to pulmonary embolism (PE). PMID- 1864062 TI - Infections at the site of a hip implant. Successful and unsuccessful management. AB - Thirty-four patients developed the complication of deep infection at the site of a hip implant (n = 35). Multiple factors in existence at the time of implant placement and the time of presentation with infection as well as the therapeutic regimen were retrospectively analyzed. Patients with successful outcomes (n = 15) were relatively younger (mean, 52 years) compared to those that had an unsuccessful outcome (n = 19; mean, 65 years; p less than 0.01). No other factors were predictive of the outcome of treatment. Implant extirpation, expedient wound closure, and, when necessary, muscle transposition favored a successful outcome. Implant retention and open wound packing resulted in prolonged wound healing and, sometimes, hip disarticulation or death. PMID- 1864063 TI - Blood loss in total knee arthroplasty. AB - Over a two-year period, 112 consecutive primary total knee arthroplasties (TKA) were performed according to a standard protocol and were evaluated to determine the effects of intraoperative tourniquet deflation, suction drainage, and immediate continuous passive motion (CPM) on blood loss and the need for blood transfusions. It has been reported that these measures lead to increased morbidity following TKA. The tourniquet was deflated before closure, hemostasis was obtained, and two suction drains were placed for 24 to 48 hours. CPM was started immediately, and continued for a mean of seven days. Serial hematocrits (Hct) were obtained. Mean age of the 64 males and 48 females was 65 years. The diagnosis was osteoarthritis in 86% and rheumatoid arthritis in 14%. Seventy three percent of the prostheses were cemented and 27% were uncemented. The mean tourniquet time was 104 minutes and the mean length of surgery was 140 minutes. Blood loss measured at surgery averaged 222 ml. Total calculated blood loss averaged 794 ml, but was higher for patients with a cemented versus uncemented prosthesis (p less than .05), and males versus females (p less than .005). It was not related to diagnosis, tourniquet time, or length of surgery. Of the 38% of patients requiring a transfusion (mean, 2.2 units), there was not a significantly greater drop in Hct (from 36.6 to 26.5; change, 10.1) when compared to patients not receiving a transfusion (from 43.1 to 32.5; change, 10.6). Therefore, the need for transfusion was related to preoperative Hct and not the intraoperative or postoperative blood loss.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864064 TI - Epidemiologic studies of oral mucosal conditions--methodologic issues. AB - The methods used in the international English-language literature of epidemiologic investigations of oral mucosal conditions were reviewed. Methods used to study leukoplakia, lichen planus, recurrent herpes labialis, recurrent aphthous ulcers, geographic tongue and candidiasis are highlighted. In addition, studies of the full range of pathologies documented in a population were reviewed. The methodologic issues raised by the epidemiologic literature as well as those to be considered for future studies of oral mucosal conditions are presented. Emphasis is placed on study population selection, diagnostic criteria development, type and training of examiners, risk factor assessment and issues related to data collection, analysis and reporting. PMID- 1864065 TI - Social factors and tooth loss in a 12-year follow-up study of women in Gothenburg, Sweden. AB - Representative samples of women in different age groups in Gothenburg, Sweden, were examined by means of panoramic radiography in 1968-69 and in 1980-81. Edentulousness and number of remaining teeth were assessed from the radiographs. Data on socioeconomic conditions, educational background and dental care attendance were obtained from a questionnaire. Cross-sectional results showed that improvements in dental status had occurred irrespective of socioeconomic conditions and educational levels and that differences between groups had decreased over the 12-yr period. Dental care attendance was high in all socioeconomic groups, but differences noted in 1968-69 remained in 1980-81. PMID- 1864066 TI - Relationship between number of teeth and periodontal pockets. AB - The relationship between number of teeth and the prevalence of periodontal disease is an important factor to consider when planning future needs for periodontal care. This is of particular relevance today, when the level of tooth loss is steadily reducing. The aim of the present study was to examine this relationship. Three dependent variables associated with periodontal disease were included in the analysis: 1. The probability of having pockets 4 mm or more. 2. The mean pocket depth for individuals with pockets 4 mm or more. 3. The number of pockets for individuals with pockets 4 mm or more. Age was included in the analysis as a control variable. The study population comprised 2219 individuals in the county of Trondelag, Norway. The data were analyzed using logistic regression and multiple regression analysis. The probability of having pockets 4 mm or more increased with increasing number of teeth. The average pocket depth decreased with increasing number of teeth. There was no relationship between number of pockets and number of teeth. The increase in the probability of having pockets with a marginal increase in number of teeth was greatest for those aged 53 years and above. It is concluded that this group of people are likely to have the greatest need for periodontal care. PMID- 1864067 TI - Caries prevalence and salivary mutans streptococci in 0-2-year-old children of Japan. AB - The prevalence of caries and the number and species distribution of salivary mutans streptococci in 356 children (aged 0-2 yr old) in Japan were examined twice at an interval of 1 yr. No mutans streptococci were isolated from the predentate children. The detection rate of mutans streptococci and the prevalence of caries increased with age. Mutans streptococci were isolated from 39.9% of the subjects. The majority of isolates were identified as Streptococcus mutans. The concentration of mutans streptococci correlated with the number of erupted teeth (r = 0.339). In addition, the concentration of mutans streptococci was more closely correlated to the caries prevalence of the next year (r = 0.465) than that of the year when the salivary concentration of mutans streptococci was first evaluated (r = 0.368). The children who had no caries but harbored mutans streptococci in the first year showed significantly higher caries prevalence in the next year than did the children with neither caries nor mutans streptococci. These results indicate that the establishment of mutans streptococci is associated with caries initiation in early childhood. PMID- 1864068 TI - Epidemiological study of oral leukoplakia based on mass screening for oral mucosal diseases in a selected Japanese population. AB - The purpose of this study was 1) to show the epidemiological status of oral leukoplakia in a selected population of 3131 Japanese (504 women, 2627 men, aged 18-63 yr, mean age 35.9 yr), and 2) to estimate of the validity of the diagnosis of oral leukoplakia by general practitioners. Seventy-seven individuals were detected as having leukoplakia, a prevalence of 2.5%; 2.7% and 1.0% for men and women, respectively, a difference that is statistically significant (P less than 0.001). The percentage of smokers was 75.3% for patients with leukoplakia and 47.8% for individuals detected as not having leukoplakia, a difference which is statistically significant (P less than 0.001). Of 77 leukoplakia patients, 37 cases (48.1%) received a clinically confirmed diagnosis and 27 patients were diagnosed in further examination as having leukoplakia. These results can also be expressed by a positive predictive value of 0.73 and a false positive ratio of 0.27 for the diagnosis of leukoplakia in the primary mass screening by general practitioners. The results of this study suggest that in order to carry out an efficient oral health program in Japan, the objects for mass screening for leukoplakia might be better limited to men over 30 and women over 40 yr of age. PMID- 1864069 TI - Teeth, tooth spaces, and prosthetic appliances in elderly men in Malmo, Sweden. AB - A group of 483 men, all of whom were 68 or 69 yr old and had lived for a long time in the city of Malmo were examined with regard to number of teeth present, removable dentures, fixed bridges, and tooth spaces. 76.4% had one or more natural teeth remaining, 59.2% had removable dentures, and 0.2% were edentulous and without dentures. The mean number of teeth present in a fixed dentition calculated on dentate subjects was 16.21 +/- 8.02, including teeth replaced by pontics and 15.0 +/- 7.44 when natural teeth only were recorded. The number of bridges was high, 28.8% of natural dentate persons having bridgework. This cohort had fewer remaining teeth than in similar groups in other areas of Sweden, but more fixed bridges. 19.5% had open tooth spaces corresponding to one or more teeth in the visible parts of the dental arches. The availability of dentistry has been extremely good in Malmo and financial support for all types of dental care has been provided for all inhabitants since 1974. In spite of this, a low number of remaining teeth and many untreated tooth spaces in visible part of the dental arches were found, though on the other hand much fixed bridgework was found. It appears from the present study that the population tends to polarize into two groups, namely one group which takes advantage of the dental services and one which does not. PMID- 1864070 TI - Oral mucosal health and disease in institutionalized elderly in Brazil. AB - During the last decade, many studies in Europe and North America have evaluated oral conditions and dental needs in the elderly. Similar information does not exist in Brazil. The aim of this study was to determine the prevalence of oral health and disease in elderly persons living in an institution in the city of Piracicaba, State of Sao Paulo, Brazil. Of 350 elderly persons, 134 males and 136 females were interviewed and clinically examined. Less than one half had healthy mouths. 58.9% of the examined individuals showed one or more lesions in the oral mucosa, the most frequent being denture-induced stomatitis (20.0%). Fibrous hyperplasias (11.8%) and angular cheilitis (9.3%) were fairly common. Gender, use and degree of hygiene of the denture were factors statistically significantly contributing to prevalence of denture stomatitis. Precancerous lesions such as leukoplakia (3.0%), actinic cheilitis (2.6%) were uncommon but three cases of squamous carcinoma (1.1%) were revealed. This study emphasizes the need for regular oral examinations of the elderly by personnel trained in oral diagnosis. PMID- 1864071 TI - Dental caries in black preschool children in Cape Town. PMID- 1864072 TI - Fluoride in drinking water and caries progression in a Tanzanian child population. PMID- 1864073 TI - DMFT counts in the adult population of Ljubljana, Yugoslavia. PMID- 1864074 TI - Attitudes of nursing and rest home administrators toward deinstitutionalized elders with psychiatric disorders. AB - The administrators of 92 nursing homes and rest homes in western Massachusetts were surveyed on their experiences with elderly residents with a history of psychiatric hospitalization and their willingness to admit such individuals in the future. A majority of those who had admitted deinstitutionalized elders with chronic psychiatric disorders reported having experienced severe problems with them. Most of the problems involved the resident going into crisis or producing some highly disruptive behavior. Although two-thirds of the facilities had admitted elders who had been deinstitutionalized from a public psychiatric hospital, only one-quarter clearly planned to do so in the future. Three quarters of the administrators reported that they did not have the support services that the deinstitutionalized elders in their facilities needed. A comparison of the services reported to be important and those reported to be available suggest that simply increasing the availability of psychiatric support services would probably not influence administrators to admit elders with chronic mental illness in the future. PMID- 1864075 TI - Acknowledging abuse backgrounds of intensive case management clients. AB - Routine inquiry about abuse experiences as children and adults yielded high levels of positive responses among 89 intensive case management clients. Through structured interviews administered by their case managers, clients disclosed backgrounds in families with one or more alcoholic adults, incest, other childhood sexual abuse, and extensive physical abuse. Gender played a major role. Being an ACOA also predicted extensive additional abuse. Clients were not treated for abuse, nor diagnosed for its impact, nor responded to when they initiated discussion with mental health providers. Later outcomes include frequent hospitalizations, substance abuse and self-mutilation. PMID- 1864076 TI - Support groups for parents of children with emotional disorders: a comparison of members and non-members. AB - This study involving more than 800 parents whose children have emotional disorders focuses on comparisons between parents who are members of support groups and those who are not. While no difference was found between members and non-members on most demographic variables, members reported needing and using more information and services and found each more difficult to locate than non members. Thirty-one percent of all respondents identified involvement with other parents as the most helpful activity in coping with their child's problems. PMID- 1864077 TI - Parents of children with emotional disorders: issues for consideration and practice. AB - Parents with children who have serious emotional disorders face significant personal and family issues in their parental role. Professionals providing services to these families must be sensitive to a variety of issues if they are to provide an emphathic context when these families are seeking help. This paper will explore the stress these families incur, the loss they experience, and the resources needed for coping and the preservation of family integrity. Practice implications will be addressed. PMID- 1864078 TI - Training Ph.D. psychologists for rural service: a report from Nebraska. AB - The Clinical Psychology Training Program at the University of Nebraska-Lincoln developed a rural mental health specialty to train psychologists to work in rural settings. Preliminary data indicate that the project was relatively successful in placing graduates in rural practice. But the needs for practitioners in rural communities clearly are greater than training programs can meet. Relying on doctoral psychologists for clinical work in rural communities may not be the best strategy in workforce planning. PMID- 1864079 TI - Quantitation of dimethyl sulfoxide in solutions and tissues by high-performance liquid chromatography. AB - We have developed a rapid and simple method to determine the level of dimethyl sulfoxide (Me2SO) in both solutions and tissue samples. For analysis of Me2SO in a cryopreservation medium, the solution is simply diluted in 10% (vol/vol) methanol and centrifuged. Then an aliquot of the supernatant is assayed by high performance liquid chromatography. For tissue samples, the wet weight is measured and the intact sample is extracted with 10% (vol/vol) methanol (e.g., 10 ml/g wet wt) in a sealed vial. The extract is then diluted and centrifuged, and an aliquot of the supernatant is assayed. The dry weight of the tissue is measured after the methanol-extracted sample is placed into either for 2 h and air-dried overnight. The water content of the tissue is calculated as the difference between the wet and the dry weights. The concentration of Me2SO in the aqueous compartment of the tissue can then be calculated by taking into account the concentration of Me2SO in the extract and the dilution factor, based on the tissue water volume and the volume of methanol used to extract the Me2SO. The calculated values for porcine myocardium samples correlated 1:1 with the actual Me2SO concentrations in the solutions in which the tissue samples were equilibrated. Finally, we present results documenting the usefulness of this assay by following the time course of Me2SO penetration into core versus peripheral regions of 1-cm3 samples of porcine myocardium. PMID- 1864080 TI - Biotransformation activity in vitrified human liver slices. AB - In vitro testing of human liver for biotransformation or xenobiotic metabolism studies has been limited by unpredictable acquisition of samples. Consequently, it has become necessary to consider methods to cryopreserve and store these samples whenever they do become available for culture of the revived tissue at a more convenient time. Human liver slices were cryopreserved by vitrification, which allows for the transfer of aqueous media to low temperatures (-196 degrees C) without the formation of ice crystals. Human liver slices were exposed to increasing concentrations of 1,2-propanediol up to a final concentration of 4.76 M in fetal calf serum. Slices were then vitrified by direct immersion into liquid nitrogen and warmed by submersion in 37 degrees C fetal calf serum. Warming was done either immediately or after 4 and 8 weeks of storage under liquid nitrogen. The effects of vitrification, storage time, and warming on biotransformation were determined by assessing the integrated metabolism of 7-ethoxycoumarin (7-EC). Vitrified or fresh human liver slices were exposed to 50 microM 7-EC and its primary metabolite 7-hydroxycoumarin (7-HC) in organ culture for up to 6 hr. Metabolite production of both fresh and vitrified liver slices was compared. Retention of the inherent biotransformation rate was usually high and seemed independent of storage time. Integration of both cytochrome P450-mediated and secondary conjugation processes was retained in cryopreserved tissue. Vitrification offers a way to cryopreserve human liver slices for the study of xenobiotic metabolism in humans. PMID- 1864081 TI - Effects of method of preservation on functions of livers from fed and fasted rabbits. AB - Livers from fed, fasted (48 h) and glucose-fed rabbits were preserved for 24 and 48 h by either simple cold storage (CS) or continuous machine perfusion (MP) with the University of Wisconsin preservation solutions. After preservation liver functions were measured by isolated perfusion of the liver (at 37 degrees C) for 2 h. Fasting caused an 85% reduction in the concentration of glycogen in the liver but no change in ATP or glutathione. Glucose feeding suppressed the loss of glycogen (39% loss). After 24 h preservation by CS livers from fed or fasted animals were similar including bile production (6.2 +/- 0.5 and 5.6 +/- 0.4 ml/2 h, 100 g, respectively), hepatocellular injury (LDH release = 965 +/- 100 and 1049 +/- 284 U/liter), and concentrations of ATP (1.17 +/- 0.15 and 1.18 +/- 0.04 mumol/g, glutathione (1.94 +/- 0.51 and 2.35 +/- 0.26 mumol/g, respectively), and K:Na ratio (6.7 +/- 1.0 and 7.7 +/- 0.5, respectively). After 48 h CS livers from fed animals were superior to livers from fasted animals including significantly more bile production (5.0 +/- 0.9 vs 2.0 +/- 0.3 ml/2 h, 100 g), less LDH release (1123 +/- 98 vs 3701 +/- 562 U/liter), higher concentration of ATP (0.50 +/- 0.16 vs 0.33 +/- 0.07 mumol/g) and glutathione (0.93 +/- 0.14 vs 0.30 +/- 0.13 mumol/g), and a larger K:Na ratio (7.4 vs 1.5). Livers from fed animals were also better preserved than livers from fasted animals when the method was machine perfusion. The decrease in liver functions in livers from fasted animals preserved for 48 h by CS or MP was prevented by feeding glucose. Glucose feeding increased bile formation after 48 h CS preservation from 2.0 +/- 0.3 (fasted) to 6.9 +/- 1.2 ml/2 h, 100 g; LDH release was reduced from 3701 +/- 562 (fasted) to 1450 +/- 154 U/liter; ATP was increased from 0.33 +/- 0.07 (fasted) to 1.63 +/- 0.18 mumol/g; glutathione was increased from 0.30 +/- 0.01 (fasted) to 2.17 +/- 0.30 mumol g; and K:Na ratio was increased from 1.5 +/- 0.9 to 5.3 +/- 1.0. This study shows that the nutritional status of the donor can affect the quality of liver preservation. The improvement in preservation by feeding rabbits only glucose suggests that glycogen is an important metabolite for successful liver preservation. Glycogen may be a source for ATP synthesis during the early period of reperfusion of preserved livers. PMID- 1864082 TI - The prevention of erythrocyte swelling upon dilution after freezing and thawing. AB - Cellular swelling of erythrocytes exposed to Me2SO during freezing and thawing may lead to hemolysis upon dilution of the cryoprotectant with pure electrolyte buffer. Excessive cell swelling is effectively avoided by exposing the RBC to the nonpenetrating sorbitol after thawing and before dilution. Due to the initial reduction in volume by sorbitol, cell swelling upon dilution may not cause hemolysis particularly with concentrations of 0.05 to 0.15 M of sorbitol in the diluting electrolyte buffer. Membrane damage incurred during freezing and thawing is particularly pronounced with the older red cell population, while the younger population membrane integrity can be preserved to an optimal degree. PMID- 1864083 TI - Cryosurvival of Trichomonas vaginalis during cryopreservation of human semen. AB - Despite a 90% cryosurvival of Trichomonas vaginalis in their growth medium trypticase yeast maltose (TYM) with DMSO, none of these parasites have previously been observed to survive during cryopreservation of infected human semen with glycerol (Andrologia 18, 323 (1986)). This could have been due to the failure of the culture method used to detect low numbers of survivors. The prospects of possible transmission of T. vaginalis by artificial insemination with cryobanked (-196 degrees C) semen prompted an investigation of the cryosurvival of this parasite in the presence of semen with the cryoprotectant glycerol, using a more sensitive culture method for viability evaluation. Semen and seminal fluid from the same 23 ejaculates, as well as culture medium, were inoculated with small clinical numbers of T. vaginalis and evaluated as to their survival before and after cryopreservation. Results indicated: (i) The highest cryosurvival of T. vaginalis (4.5%) was in cryobanked (glycerolated) semen, (ii) semen, as well as glycerol, shows cryoprotective action, and (iii) glycerol reduced survival of parasites in semen, seminal fluid, and TYM medium during exposure prior to freezing. Clinical information on infectivity of small numbers of T. vaginalis and the data presented here suggests that these organisms could be transmitted by artificial insemination with infected cryobanked human semen. PMID- 1864084 TI - Ca2+ action on the stability of egg phosphatidylcholine sonicated vesicles during freeze-thaw cycles. AB - The stability of unilamellar vesicles during freeze-thaw cycles strongly depends on the Ca2+ concentration in the aqueous solution. Experiments performed at equal ionic strengths with Na+ and Ca2+ solutions indicate that the effect observed is specific for Ca2+. This is interpreted to be a consequence of the adsorption of Ca2+ on the vesicle bilayers. The variation of lipid and Ca2+ concentrations indicates that stability is achieved at a particular Ca2+/lipid ratio of 8 mol/mol above which vesicles are stable. The stability appears to be mainly conferred by the external Ca2+ in both slow and rapid cycles, independent of the ionic vesicle content. However, internal Ca2+ seems to increase the stability according to the F/T cycle rate to some extent in the absence of Ca2+ in the external solution. PMID- 1864085 TI - Cooling to heat of fusion (HOF), followed by rapid rewarming, does not reduce the integrity of microvascular corrosion casts. AB - This study utilized microvascular corrosion casting techniques to evaluate changes in the microvascular patency of rat hindpaws cooled to four different subzero temperatures. Left hindpaws of anesthetized rats in group 1 were cooled to -5 degrees C, in group 2 to -15 degrees C, in group 3 to heat of fusion (HOF), and in group 4 to HOF and then to -15 degrees C. Although freezing did not take place in the hindpaws of groups 1 and 2, initiation of freezing in the tissues, as indicated by HOF, did occur in groups 3 and 4. Cooled hindpaws were rapidly rewarmed. Right hindpaws served as controls. Microvascular corrosion casts were made from the left and right hindpaws of all animals. There was no significant difference when the mean cast weights of cooled hindpaws from groups 1, 2, and 3 were compared to the mean cast weights of their respective control hindpaws. In group 4, there was a significant difference (P less than 0.05) when the mean cast weight of the cooled hindpaws (47.69 +/- 9.05, mg +/- SEM) was compared to that of the control hindpaws (80.63 +/- 12.23). Since, in this acute experiment, a loss of vascular integrity occurred when the hindpaws in group 4 were cooled to 15 degrees C after reaching HOF, the initiation of freezing alone was not sufficient to reduce mean cast weight. PMID- 1864086 TI - Design and organization of the herpetic eye disease study (HEDS). AB - The Herpetic Eye Disease Study (HEDS) includes three double-masked, placebo controlled clinical trials for potentially blinding herpes simplex virus (HSV) eye infections. One study compares a tapering dosage of topical prednisolone or placebo eye drops for HSV stromal keratitis (HEDS-SKN). Two other trials compare oral acyclovir to placebo capsules for HSV stromal keratitis (HEDS-SKS) or iridocyclitis (HEDS-IRT) in patients on a tapering dosage of topical prednisolone drops. All medications are administered for 10 weeks. Outcome is judged by time to recurrent disease or treatment failure. This paper presents the design, estimated sample size and recruitment as of July 25, 1990. PMID- 1864087 TI - A community study of ocular herpes simplex. AB - A recent epidemiologic study of ocular herpes simplex in 151 patients over a 33 year old period in Rochester, Minnesota has challenged some of the clinical and epidemiologic tenets about the disease. The incidence rate for new and recurrent cases and the prevalence rate was calculated and projected to the white U.S. population. The recurrence rate assessed by life table methods were determined for up to 20 years after the first episode and these rates rose following repeated episodes. Previous studies in the same community allow comparison of the incidence rates with other herpetic diseases. This community based study more accurately defines many of the features of the disease such as the prevalence among the sexes, the increasing age at presentation, the frequency of bilateral disease, the relationship of the initial disease to the future recurrence patterns, the frequency of lid, epithelial, stromal, and uveitis in an unselected community population, and the final visual outcome. This data estimates more accurately the morbidity and social impact of the condition. PMID- 1864088 TI - Anterior segment ischemia in chronic herpes simplex keratouveitis. AB - Six patients with chronic herpes simplex keratouveitis developed a rapidly progressive ocular inflammation unresponsive to corticosteroid and antiviral therapy. Severe secondary glaucoma unresponsive to maximum medical therapy ensued and was treated by cyclocryotherapy in five patients. Ocular ischemia with secondary corneal and scleral calcification subsequently developed in all six patients. All had also received prolonged topical therapy with topical antiviral agents, corticosteroids, beta adrenergic blockers and epinephrine compounds. Three eyes eventually required enucleation for the relief of pain; one stabilized, and two others became phthisical. One of the phthisical eyes developed a secondary fungal endophthalmitis. Histopathologic examination of the three enucleated globes revealed extensive corneal, scleral and conjunctival calcification, secondary angle closure, iris and ciliary body necrosis, focal choroiditis, retinal necrosis and atrophy. The syndrome recognized in these patients appears to be a rare but devastating complication of herpes simplex keratouveitis, possibly exacerbated by the application of cyclocryotherapy and other factors. PMID- 1864089 TI - Chronic ocular zoster. AB - In a prospective open trial 40 patients suffering from acute herpes zoster ophthalmicus were treated with systemic acyclovir. An additional 10 patients were treated by topical acyclovir alone and dexamethasone eye-drops were administered to 5 of them to suppress ocular inflammation. In the topical treatment group the period of new skin lesion formation and progression of ocular inflammatory signs were significantly prolonged. Therapy with systemic acyclovir however resulted in a quick and complete resolution of ocular inflammation in all patients. Chronic ocular inflammation developed in 4 out of 10 patients treated with topical acyclovir. We consider chronic ocular zoster as a distinct clinical entity, possibly expressing a failing local immune response against VZV. PMID- 1864090 TI - Ocular ulcerative herpes following measles in Kinshasa, Zaire. AB - Eight cases of ocular ulcerative herpes following measles are reported. The clinical features are characterized by dendritic corneal ulcer (6 cases) and ulcero-erosive blepharitis associated with corneal ulcer (2 cases). Bacteriologic examination disclosed Pseudomonas aeruginosas in 2 cases. The serum level of retinol, RBP, prealbumin and albumin were generally diminished in cases of dendritic corneal ulcer. These data are discussed in relation to the onset and severity of ocular ulcerative herpes associated with measles. PMID- 1864091 TI - High-dose oral acyclovir in acute herpes zoster ophthalmicus: the end of the corticosteroid era. AB - Systemic acyclovir (ACV), a new potent anti-herpes drug, was shown to reduce effectively the morbidity in the acute phase of herpes zoster ophthalmicus (AHZO). Using high dose oral ACV (5 X 800 mg/day) our aim in this study was: (1) to compare disease profiles in the ACV-treated group and in a group of zoster patients having had no ACV, analysed retrospectively; (2) to establish if high dose ACV was able to prevent severe long term complications of AHZO; and (3) to determine the present role of corticosteroids in AHZO. From 1984 to 1988, 48 patients with AHZO of less than 3 days' duration were included. All patients received at least 7 days of oral ACV (5 X 800 mg/d) associated with topical ACV. Steroids were not given unless severe uveitis occurred. Follow-up was 2 years in 43 patients and 1 year in all 48 patients. Main conclusions from our study are: 1. Ocular involvement occurred in 67% of ACV-treated cases, a rate comparable to our retrospective group (59%) and to the literature (71%). However the rate of severe long term complications was minimal (4%) when compared to our non-treated retrospective group (21%). 2. Steroid treatment was not necessary in any of the ACV-treated patients. 3. ACV was well tolerated and did not have to be discontinued in any of the patients. High dose ACV and avoidance of steroids seems to eliminate the severe complications of AHZO. PMID- 1864092 TI - Oral acyclovir in herpes zoster ophthalmicus. AB - 46 patients with acute herpes zoster ophthalmicus of less than 72 hours duration were recruited into a placebo controlled trial to assess the efficacy of oral acyclovir, 800 mg 5 times daily, in preventing or modifying ocular complications and pain. Fewer acyclovir recipients developed intraocular complications and these were less severe but neither difference was statistically significant. However, active ocular disease was significantly less common in the acyclovir group (p = 0.01) at 6 months. Pain was significantly less severe in the acyclovir group between 2 and 6 months. The proportion of patients with pain scores greater than 0 was significantly lower in the acyclovir group between 2 and 3 months. Oral acyclovir appears to modify the disease process in herpes zoster ophthalmicus, to reduce the severity and incidence of postherpetic pain and especially to protect against long-term ocular complications. PMID- 1864093 TI - External ocular herpesvirus infections in immunodeficiency. AB - Infections of the eye with members of the herpes family of viruses (e.g. HSV, CMV, VZV) are frequent manifestations of acquired and inherited defects in cell mediated immunity. Herpesvirus infections in the immunocompromised may reflect frequent viral reactivation from the latent state, as well as extensive productive infection of ocular structures following reactivation or primary infection. A review of experimental and clinical studies of both acquired and inherited immune dysfunction implicates specific immune mechanisms influencing the establishment of latency, viral reactivation and the control of active viral replication in ocular tissues. PMID- 1864094 TI - Exercise capacity in patients with chronic obstructive pulmonary disease. PMID- 1864095 TI - Cardiopulmonary bypass and coronary artery bypass graft. Are the risks necessary? PMID- 1864096 TI - Are new ventilatory modalities really different? PMID- 1864097 TI - Pulmonary medicine revisited. PMID- 1864098 TI - Neurosarcoidosis. PMID- 1864099 TI - Cardiac biopsy in patients with "primary" atrial fibrillation. Histologic evidence of occult myocardial diseases. AB - Fourteen patients (ten men and four women; mean age, 37 years) with lone atrial fibrillation (AF) (1 to 18 months' duration) were evaluated by thyroid function tests, two-dimensional echocardiography, hemodynamics, coronary angiography, and left ventricular endomyocardial biopsy, because of unresponsiveness to the usual antiarrhythmic therapy. The results of the T3, T4, TSH, and TRH tests were normal in all patients; cardiac valves and ventricular and atrial sizes (left atrium less than 40 mm) were within the normal limits; also normal were LVEDP (less than or equal to 10 mm Hg) and EF (greater than 0.50). Histologic findings were abnormal in all cases, with three patients showing cardiomyopathic changes, three other patients showing active myocarditis (lymphocytic in two and eosinophilic in one), and eight patients with nonspecific necrosis or fibrosis or both. Steroids (prednisone; 50 mg/m2 of body surface area daily) used in addition to antiarrhythmic therapy in patients with eosinophilic and lymphocytic active myocarditis were able to cause reversion to sinus rhythm, while the other patients continued to have AF. This study documents that occult myocardial diseases (myocarditis, cardiomyopathy, and nonspecific necrosis or fibrosis) can underlie "primary" AF. The addition of steroids to antiarrhythmic therapy in patients with refractory AF and histologic evidence of active myocarditis seems to be useful in controlling the arrhythmia. PMID- 1864100 TI - Treatment of bronchial asthma with terbutaline inhaled by conespacer combined with positive expiratory pressure mask. AB - The influence of positive expiratory pressure (PEP) applied during inhalation of a beta 2-agonist in treatment of bronchial asthma was investigated in a randomized crossover study with two-week treatment periods. In one period, two puffs (0.5 mg) of terbutaline was given from a metered dose inhaler and inhaled through a device consisting of a conespacer connected to a facemask giving PEP (10 to 15 cm H2O). In a second period, terbutaline 0.5 mg was inhaled similarly but without PEP, and in a third period placebo spray was inhaled with PEP. Treatments were given three times daily. Peak expiratory flow (PEF) was measured before and after each inhalation and symptom scores for dyspnea, cough, and mucus production were noted in a diary. All treatments increased PEF significantly (p less than 0.0001). The mean increase was 32 L/min during treatment with terbutaline and PEP. This was greater than the increase of 25 L/min during terbutaline treatment (p = 0.005). The increase in PEF during terbutaline treatment was significantly higher than the achieved 18 L/min during PEP (p = 0.026). The study showed improved bronchodilation when PEP was combined with inhalation of beta 2-agonist compared with beta 2-agonist alone. PMID- 1864101 TI - A survey of the current use and methods of analysis of bronchoprovocational challenges. AB - The purpose of this study was to survey the current techniques and methods of analysis in bronchoprovocational challenges currently in use. A questionnaire was sent to 94 investigators who had recently published an article in which a bronchoprovocational technique was used. They were asked to answer questions regarding the techniques used in challenge procedures and to calculate the results of ten histamine challenges which had previously been performed in our laboratory. Forty-four responded; 32 of these gave specific results for the histamine challenge. The most common provocative agent utilized was methacholine (62 percent), and that most used delivery mode was a dosimeter for delivery (55 percent). The most common provocative agent utilized was methacholine (62 percent) and the most used delivery mode was a dosimeter (55 percent). PMID- 1864102 TI - Outcome of assessments for occupational asthma. AB - Among 154 referrals to a university hospital clinic for assessment of possible occupational asthma, the feasibility and results of different investigations were assessed using a consistent approach to all patients. A positive skin test to a workplace allergen (14 percent of all subjects), positive peak flow workplace changes (12 percent), improvement in methacholine response on holiday (9 percent), and/or positive specific challenge testing (14 percent) supported the diagnosis of occupational asthma in 61 subjects (39 percent of the total referrals). Fifty-one of these were related to a workplace sensitizer and ten to a presumed irritant. Occupational asthma was excluded in 48 subjects (31 percent) who had normal methacholine responsiveness within 24 hours of work (22 percent of the 154 subjects), peak flow readings no worse at work than on holidays (14 percent of the total referrals) and/or negative specific challenge testing (10 percent of the total referrals). Insufficient information could be obtained for a diagnosis in the remaining 45 subjects (28 percent). No single investigation was considered diagnostic in this study, as each could be positive or negative for other reasons. PMID- 1864103 TI - Artificial intelligence-assisted occupational lung disease diagnosis. AB - An artificial intelligence expert-based system for facilitating the clinical recognition of occupational and environmental factors in lung disease has been developed in a pilot fashion. It utilizes a knowledge representation scheme to capture relevant clinical knowledge into structures about specific objects (jobs, diseases, etc) and pairwise relations between objects. Quantifiers describe both the closeness of association and risk, as well as the degree of belief in the validity of a fact. An independent inference engine utilizes the knowledge, combining likelihoods and uncertainties to achieve estimates of likelihood factors for specific paths from work to illness. The system creates a series of "paths," linking work activities to disease outcomes. One path links a single period of work to a single possible disease outcome. In a preliminary trial, the number of "paths" from job to possible disease averaged 18 per subject in a general population and averaged 25 per subject in an asthmatic population. Artificial intelligence methods hold promise in the future to facilitate diagnosis in pulmonary and occupational medicine. PMID- 1864104 TI - Value of transesophageal echocardiography as an adjunct to transthoracic echocardiography in evaluation of native and prosthetic valve endocarditis. AB - To determine if transesophageal echocardiography provides better visualization of valvular vegetations than transthoracic echocardiography, we used both methods to evaluate 24 consecutive patients (mean age, 54 years; 15 female patients and nine male patients) referred for symptoms suggestive of infectious endocarditis. Ten of the 24 patients had one or more valvular prostheses. Echocardiograms were classified as positive or negative based on visualization of valvular vegetations or abscesses. Of ten patients with a final diagnosis of infectious endocarditis on extended follow-up, transthoracic echocardiography was positive in five patients. Transesophageal echocardiography not only yielded abnormal findings in all ten of these patients, but also revealed additional information in four of the five patients with abnormal transthoracic echocardiographic examinations. Among the 14 patients who, on subsequent follow-up, were found not to have infectious endocarditis, transthoracic echocardiography was normal in 13 and falsely abnormal in one. Transesophageal echocardiography revealed no evidence of infectious endocarditis in any of these patients. The ten patients who were determined to have infectious endocarditis all had positive blood cultures and no alternative cause for their clinical presentation; in seven patients in this group who underwent operative or postmortem evaluation, infectious endocarditis was confirmed. All patients without infectious endocarditis were demonstrated to have other causes for their clinical presentation. We conclude that transesophageal echocardiography is a highly valuable test in the work-up of patients with suspected infectious endocarditis, especially those patients with inconclusive or normal transthoracic echocardiograms. In addition, transesophageal echocardiography may be of benefit to patients with previously documented infectious endocarditis and a complicated clinical course in whom additional cardiac lesions are suspected but not demonstrated by transthoracic echocardiography. PMID- 1864105 TI - Effect of postural changes and isometric exercise on Doppler-derived measurements of diastolic function in normal subjects. AB - To determine if simple maneuvers that occur in daily life, such as changes in body position and isometric handgrip exercise, affect Doppler-derived measurements of diastolic function, we studied 22 normal male subjects in the supine position at rest and during several postural manipulations and during handgrip exercise. Comparison of values obtained in the 80 degrees upright tilt position with those obtained in the standard supine position revealed significant decreases in early diastolic flow velocity (peak E) (-25 +/- 3 percent; p less than 0.001), late diastolic flow velocity (peak A) (-9 +/- 3 percent; p less than 0.01), and the ratio of early to late flow velocities (E/A ratio) (-17 +/- 4 percent; significant increases in deceleration time (+55 +/- 10 percent; p less than 0.001) and isovolumic relaxation time (+38 +/- 4 percent; p less than 0.001). Comparison of values obtained with supine isometric exercise with those obtained during the preceding supine resting state revealed significant decreases in peak E (-12 +/- 3 percent; p less than 0.001) and the E/A ratio (-21 +/- 4 percent; p less than 0.001) and significant increases in peak A (+15 +/- 4 percent; p less than 0.001) and isovolumic relaxation time (+16 +/- 3 percent; p less than 0.001). The response of Doppler-derived measurements of diastolic function to postural changes and isometric exercise is complex and multifactorial. Interpretation of these measurements must take into account changes in loading conditions. PMID- 1864106 TI - Measurement of maximal static respiratory pressures at the mouth with different air leaks. AB - The effect of two different circuit leaks on the measurement of maximal static inspiratory and expiratory pressures at the mouth (Pimax, Pemax) was assessed in 70 patients with respiratory disease. Patients were divided into three groups with similar anthropometric and spirometric characteristics. The first group (30 patients) had their Pmax measured with a leak of 2.0 mm internal diameter (ID) and 37 mm length (as proposed by T. Ringqvist) and repeated with a second leak of 1.0 mm ID and 15 mm length (as recommended by J. L. Clausen). The two measurements were done in random order. Measurements for the other two groups (20 patients each) were taken with one or another, the two leaks randomly alternated with no leak. Pimax measurements obtained with Ringqvist's leak were 17 percent (p less than 0.005) lower than those with Clausen's leak and 22 percent (p less than 0.005) lower than those with no leak. Pemax measurements performed with Ringqvist's leak in place were 11 percent (p less than 0.005) lower than those with Clausen's leak and 11 percent (p less than 0.005) lower than those obtained with no leak. The comparison between Clausen's leak and no leak showed no statistically significant difference. We conclude that whenever the effect of pressure generated in the mouth is to be avoided in the measurement of respiratory Pmax, a leak of the size proposed by Ringqvist is to be preferred. PMID- 1864107 TI - Nocturnal hypoxemia as a determinant of vigilance impairment in sleep apnea syndrome. AB - In sleep apnea syndrome (SAS), vigilance impairment is typically associated with highly disrupted sleep, but recently, nocturnal hypoxemia has also been identified as a second pathogenetic factor in patients with a high degree of desaturation. However, although sleep disruption has been demonstrated to play a role in both the propensity to fall asleep and the capacity to stay awake, the role of nocturnal hypoxemia has been implicated only in the latter. In the present study, both sleep disruption and nocturnal hypoxemia were assessed in 20 moderately to severely apneic patients. During the day, vigilance was assessed both by the multiple sleep latency test (MSLT), as a measure of the propensity to fall asleep, and by the four-choice reaction time test (FCRTT), as a measure of the capacity to stay awake in a performance task. Severity of nocturnal hypoxemia was found to predict performance on the MSLT, as well as on the FCRTT, but sleep disruption was found to predict performance only on the FCRTT. These results suggest that in moderately to severely affected SAS patients, nocturnal hypoxemia may play a primary role in the pathogenesis of vigilance impairment. PMID- 1864108 TI - Noninvasive measurement of central venous pressure by neck inductive plethysmography. AB - Bedside estimation of the height at which the internal jugular veins collapse, referenced to a standard hemodynamic location, theoretically reflects central venous pressure. This method has never been demonstrated as accurate when compared to invasive CVP measurements because of the great clinical skills and time required to visually identify the internal jugular venous waveform. Since the principles of the bedside method are sound, we utilized them in conjunction with the neck inductive plethysmograph, a device which has the capability of recording internal jugular venous and carotid arterial waveforms. The respiratory distortion of these vascular waveforms was eliminated by employing a digital bandpass filter, making it easy to identify the venous and arterial waveforms on the videoscreen of a personal computer. The upper torso was positioned while observing the videoscreen until the vascular waveform was seen as a mixed arteriovenous waveform, signifying intermittent internal jugular venous collapse. The height of the internal jugular vein above the phlebostatic axis was obtained by external measurement and recorded as CVPni in cm H2O. In 43 patients, 86 percent of CVPni (NIP) values fell within 20 percent CVPi (invasive catheter measurements) over a range of CVP from 0 to 19 cm H2O. In an additional seven patients, CVPi was greater than the height that the upper torso could be elevated and an arterial waveform could not be obtained. Here, CVPni was recorded as the value at least exceeding the value measured. In two other patients, obstruction of an internal jugular vein gave spuriously low values of CVPni. Our study indicates that this new neck inductive plethysmographic method is accurate compared to invasive catheter measurements of CVP and should serve as a safe, noninvasive alternative in situations where such measurements are required. PMID- 1864109 TI - Phrenic nerve injury. A prospective study. AB - In cardiac surgery, topical iced saline solution slush has become an important adjunct in maintaining myocardial hypothermia during cardioplegic arrest. One complication of this technique is phrenic nerve injury (PNI). In an attempt to reduce the incidence of PNI, a prospective study was undertaken to evaluate the impact of phrenic nerve insulation on PNI during cardiac surgery. Seventy-six consecutive patients who underwent coronary revascularization constituted the control group (CG) and were compared with 76 patients who underwent a similar procedure with the addition of phrenic nerve insulation. In the intervention group (IG), a foam insulation pad was placed between the heart and the pericardium in an effort to reduce exposure of the phrenic nerve to iced saline solution slush. There was no difference in major demographic descriptors or operative variables between the CG and the IG, except that the internal mammary artery was used more frequently in the IG (64 percent vs 36 percent, p = 0.0006). The in-hospital mortality was similar between the groups (CG, 0.0 percent; IG, 1.3 percent; p = 1.0); however, the incidence of roentgenographically diagnosed PNI was much greater in the CG (14/76 patients [18 percent] vs 0/76 patients [0 percent]; p = 0.0006). Patients with and without PNI were similar with regard to age, gender, aortic cross clamp time, cardiopulmonary bypass time, and number of grafts (p greater than 0.05). All unilateral PNI occurred on the left. Three patients with bilateral PNI required tracheostomy and prolonged mechanical ventilation. In-hospital mortality was similar for patients with and without PNI (0 percent vs 0.7 percent), but mean postoperative hospital stay for patients with clinically diagnosed PNI was longer than for those without PNI (32 vs 11 days, p = 0.04). This prospective study demonstrates that the incidence of PNI can be significantly reduced by the routine use of phrenic nerve insulation. PMID- 1864110 TI - Prognostic value of bronchoalveolar lavage lymphocyte count in recently diagnosed pulmonary sarcoidosis. AB - We prospectively looked at the prognostic value of bronchoalveolar lavage (BAL) lymphocyte count in 98 patients with recently diagnosed (less than 4 months) untreated sarcoidosis. These 50 men and 48 women (mean age, 37.4) were followed up for a period of 6 to 60 months (mean, 25.6), and were clinically evaluated every three to six months with repeated chest roentgenograms and pulmonary function tests. Twenty-four patients required steroid treatment during the study period. The proportion of treated patients was not significantly higher in the group presenting a BAL lymphocyte count less than or equal to 30 percent at diagnosis than in the group with fewer lymphocytes (31.9 and 17.7 percent of total group respectively, p = 0.10). No significant change in TLC, FRC, FVC, FEV1 or DLCO was found at follow-up between the groups with or without an initial high lymphocyte count. In the treated group, BAL lymphocyte percent weakly correlated with the improvement of FEV1 and FVC while on steroid treatment (mean duration: 3.5 months): r = 0.41, p = 0.031 and r = 0.36, p = 0.05 respectively; no correlation was found with lung volumes and DCO. We conclude that BAL lymphocyte count at the time of diagnosis is not a helpful predictor of lung function deterioration in recently diagnosed sarcoidosis and is not very useful in predicting response to treatment. PMID- 1864111 TI - Respiratory symptoms in Indian women using domestic cooking fuels. AB - The effect of domestic cooking fuels producing various respiratory symptoms was studied in 3,701 women. Of these, 3,608 were nonsmoking women who used four different types of cooking fuels: biomass, LPG, kerosene, and mixed fuels. The overall respiratory symptoms were observed in 13 percent of patients. Mixed fuel users experienced more respiratory symptoms (16.7 percent), followed by biomass (12.6 percent), stove (11.4 percent), and LPG (9.9 percent). Chronic bronchitis in chulla users was significantly higher than that in kerosene and LPG users (p less than 0.05). Dyspnea and postnasal drip were significantly higher in the women using mixed fuels. Smoking women who are also exposed to cooking fuels experienced respiratory symptoms more often than nonsmokers (33.3 percent vs 13 percent). PMID- 1864112 TI - Chronic inflammation is associated with an increased proportion of goblet cells recovered by bronchial lavage. AB - To evaluate the possibility that bronchoalveolar lavage could provide sufficient respiratory epithelial cells to quantify changes in epithelial cell types associated with chronic inflammation, we examined the epithelial cells obtained in the first infused (20 ml) aliquots that were processed separately from later aliquots, a process known to enrich for bronchial contents. Epithelial cells, including ciliated cells, goblet cells, and fragments of desquamated epithelium, were easily identified after preparation by cytocentrifugation and staining with a modified Giemsa stain. Quantification of the columnar cell types revealed that those with chronic bronchitis and asymptomatic smokers have increased goblet cells as a percentage of the total columnar epithelial cells (chronic bronchitics 36 +/- 2 percent, asymptomatic smokers 22 +/- 2 percent) compared with normal subjects (9 +/- 1 percent, p less than 0.001, ANOVA). Significantly, the goblet cell percentage was strongly correlated with other measures of bronchitis and measures of airflow obstruction such as the bronchitis index, a visually derived score at bronchoscopy of airway inflammation (r = 0.72, p less than 0.001), the percent neutrophils in the first infused aliquots (r = 0.44, p less than 0.05), and the FEV1 percent (r = -0.74, p less than 0.001). Thus, bronchoalveolar lavage is capable of providing sufficient bronchial epithelial cells for analysis, and the changes seen in the spectrum of columnar epithelial cells may reflect important underlying pathologic changes. PMID- 1864113 TI - Urinary fibrinopeptide A in evaluation of patients with suspected acute pulmonary embolism. A prospective pilot study. AB - This pilot study assessed the urinary fibrinopeptide A (uFPA) levels and the combination of uFPA test plus ventilation/perfusion (V/Q) scan in the diagnostic evaluation of acute pulmonary embolism (PE). One hundred consecutive patients were studied prospectively. Twenty-nine patients fulfilled diagnostic criteria defined in this study (seven with and 22 without PE). The uFPA concentration was significantly higher in patients with than without PE (41.1 +/- 2.6 vs 4.8 +/- 2.5 ng/mg of creatinine, p less than 0.0001). In all patients with PE, the uFPA levels were higher than threshold value derived by adding 2 standard deviations to the mean uFPA concentration of patients without PE. In patients without PE, the V/Q scan was negative in 16, the uFPA test was negative in 18, and at least one of the tests was negative in 21. These preliminary data suggest that a negative uFPA test may be helpful in excluding PE and that uFPA in combination with V/Q lung scans may correctly exclude PE in more patients than either test alone. Further studies in a large unselected population are needed to confirm these results. PMID- 1864114 TI - Evaluation of ultrasonically guided biopsies of mediastinal masses. AB - Eighty patients with roentgenographic evidence of mediastinal abnormalities were examined with ultrasonography. Fifty-four lesions were malignant, and 26 lesions were benign. The histologic diagnoses were confirmed by ultrasonically guided fine needle aspiration/cutting needle (Tru-Cut) biopsy, surgical specimens, or transbronchial biopsy. There were no unique ultrasonographic features for diagnosis of specific tumors. Ultrasonically guided aspiration biopsies (UGAB) were performed in 44 of the malignant lesions and in 14 of the benign lesions (nine of the noncystic lesions and five of the cystic lesions). Cytologic diagnosis of malignancies was obtained in 34 (77 percent) of these 44 malignancies; however, accurate histologic classifications of malignancies were achieved in only 24 (55 percent). Accurate diagnoses were achieved in only three (33 percent) of the nine noncystic benign lesions. Ultrasonically guided cutting biopsies (UGCB) were performed in 24 malignant and five benign lesions. All attempts yielded satisfactory specimens for histologic diagnosis. Using UGAB and UGCB together, a positive diagnosis was achieved in 89 percent (39/44) of the malignancies, and accurate histologic diagnosis was achieved in 89 percent and 78 percent (7/9) in malignant and benign noncystic lesions, respectively. Correct histologic diagnosis with UGAB alone is lower in thymoma (55 percent [6/11]) and lymphoma (30 percent [3/10]) but higher in lung cancer (67 percent [8/12]) and metastatic cancer (78 percent [7/9]). There were no complications in this series. We conclude that ultrasonography with UGAB has a high diagnostic yield in diagnosing mediastinal tumors, and UGCB is necessary for thymic tumors, lymphoma, and benign lesions. PMID- 1864115 TI - Pleural penetration of ciprofloxacin in patients with empyema thoracis. AB - We evaluated the pharmacokinetics of a single 200-mg dose of ciprofloxacin, administered as a 30-minute infusion, into pleural exudate in five elderly patients with empyema thoracis. Ciprofloxacin was measured by HPLC and the pharmacokinetic parameters were determined by noncompartmental methods. Mean peak serum levels 30 minutes after administration were 1.98 +/- 0.07 mg/L. Terminal serum half-lives ranged from 3.9 to 5.1 h. Mean concentrations of ciprofloxacin in pleural exudate were 1.44 +/- 0.42 mg/L at a mean time of 4.5 +/- 2.5 h. After this time, the pleural exudate level exceeded the corresponding serum twofold to tenfold. The mean percentage penetration into the inflammatory compartment was approximately 210 percent. Our data suggested that ciprofloxacin penetrates well into the pleural fluid of patients with empyema thoracis. The concentrations achieved were well above the MIC90 of most pathogens normally found in patients with empyema thoracis for a period of approximately 12 h. PMID- 1864116 TI - Assessment of bronchodilator response to a beta-adrenergic delivered from an ultrasonic nebulizer. AB - We assessed the bronchodilator response to a recently available ultrasonic nebulizer (USN) in a population of 17 stable asthmatic patients. These patients were also evaluated for bronchodilator response to two other aerosol delivery systems routinely used in standard clinical practice, the metered-dose inhaler (MDI) and the jet nebulizer (JN). Albuterol was administered from each of the delivery systems in the following manner: MDI, two actuations (180 micrograms); JN, 0.5 ml of 0.5 percent solution (2.5 mg) in 1.0 ml saline solution diluent; and USN, 0.5 ml of 0.5 percent solution (2.5 mg) in 2.5 ml saline solution diluent. Patients demonstrated significant bronchodilator responses to all three delivery systems (p less than 0.0001). The USN produced a greater percentage of increase in FEV1 15 minutes after treatment with albuterol (35.8 +/- 2.3 percent) than either the MDI (18.2 +/- 3.4 percent) or JN (20.8 +/- 3.1 percent) (p less than 0.005). The mean percentage of increase in FE1 observed over a 4-h period after treatment was also greater for the USN (26.5 +/- 2.5 percent) than either the MDI (18.8 +/- 1.8 percent) or JN (15.0 +/- 1.6 percent) (p less than 0.001). We conclude that the USN yields effective bronchodilation in a population of stable asthmatics. PMID- 1864117 TI - Response of obstructive sleep apnea to fluoxetine and protriptyline. AB - Protripyline is the pharmacologic agent most commonly used to treat obstructive sleep apnea (OSA); however, its anticholinergic side effects make it intolerable to many patients. Because serotonin may be a central respiratory stimulant and because the serotonin-uptake inhibitor, fluoxetine, is usually well tolerated, we wanted to try fluoxetine in the treatment of OSA. Therefore, we compared the effect of fluoxetine to that of protriptyline in 12 patients with OSA. Both drugs significantly decreased the proportion of REM sleep time and decreased the number of apneas or hypopneas in NREM sleep. The response to fluoxetine was equivalent to that of protriptyline; however, for the group as a whole, there was no significant improvement in the number of arterial oxygen desaturation events, the level of arterial oxygen desaturation, or the number of arousals with either agent. Although there was wide variability in the response to each medication, six of the 12 patients had good responses, including improvement in oxygenation, to either fluoxetine or protriptyline. Three patients could not complete the trial of protriptyline. We conclude that fluoxetine is beneficial to some, but not all, patients with OSA. Fluoxetine was better tolerated than protriptyline. PMID- 1864118 TI - Incidence, etiology, and outcome of nosocomial pneumonia in mechanically ventilated patients. AB - This study assessed the incidence, etiology, and consequences of ventilator associated pneumonia in 1,000 consecutive patients admitted in a medical-surgical intensive care unit (ICU). A total of 264 patients were submitted to mechanical ventilation (MV) for more than 48 hours. Fifty-eight (21.9 percent) patients developed a bacterial pneumonia after a mean of 7.9 days (range, 2 to 40 days) of MV. In addition, they were ten superinfections in nine patients, raising the mean incidence to 25.7 percent. Five patients developed secondary bacteremia, and another five had septic shock. Identification of the causative agent of pneumonia was possible in 47 episodes by means of highly specific techniques (telescoping plugged catheter, blood cultures, and/or necropsy). Thirteen (27.6 percent) of these cases were polymicrobial. The predominant pathogens isolated in the first episode of pneumonia were Gram-negative bacilli (62.6 percent), but a high incidence of Staphylococcus aureus infection (23.2 percent) was detected. Gram negative bacilli represented 66.6 percent of the total organisms isolated in superinfections. The mortality rate in the pneumonia group was 42 percent; this percentage is similar to mortality rate among MV patients without pneumonia (37 percent). We conclude that nosocomial pneumonia is a frequent complication of MV in the medical-surgical ICU. Ventilator-associated pneumonia does not appear to increase fatality in critically ill patients with a high mortality rate (38 percent); however, it significantly prolongs the length of stay in the ICU for survivors. PMID- 1864119 TI - Noninvasive face mask mechanical ventilation in patients with acute hypercapnic respiratory failure. AB - Mechanically assisted intermittent positive-pressure ventilation effectively provides ventilatory support in patients with respiratory failure but it requires placing an artificial airway. We have previously reported our successful experience delivering mechanical ventilation via a face mask (FMMV) rather than with an endotracheal tube in a pilot study of patients with acute respiratory failure. The present investigation evaluated an additional 18 patients with hypercapnic respiratory failure to determine the efficacy of FMMV in a more homogeneous group and to determine factors predicting its success. FMMV was successful in avoiding intubation in 13 of the 18 patients. A significant initial improvement in PCO2 (greater than 16 percent decrease) and in pH (from less than 7.30 to greater than 7.30) predicted success. The five patients who failed on FMMV required endotracheal intubation because of inability to improve gas exchange (three patients), apnea due to sedatives (one patient), and management of secretions (one patient). FMMV was generally well accepted with only two patients withdrawn because of intolerance of the mask. The mean duration of FMMV was 25 h. Complications were seen in only two patients (11 percent): aspiration (one patient) and mild skin necrosis (one patient). Seven patients entered the study by meeting entrance criteria after an unsuccessful extubation attempt and therefore received both forms of mechanical ventilation. All but one patient avoided reintubation, and the face mask proved to be as effective as the endotracheal tube as a conduit for delivering the mechanical tidal volume and improving gas exchange. Our findings indicate that FMMV is a viable option for short-term (one to four days) ventilatory support of patients with hypercapnic respiratory failure and insufficiency. PMID- 1864120 TI - Airway pressure release ventilation in severe acute respiratory failure. AB - Airway pressure release ventilation (APRV), a new ventilatory support technique, was compared with conventional intermittent positive-pressure ventilation plus PEEP (CPPV) in 18 patients with severe acute respiratory failure. Patients were initially stabilized on CPPV and then switched to APRV. The APRV provided effective ventilatory support in 17 of 18 patients; APRV achieved similar levels of alveolar ventilation as CPPV (for APRV, mean PaCO2 = 45.0 +/- 6.2 mm Hg; vs for CPPV, mean PaCO2 = 43.3 +/- 5.7 mm Hg), with significantly lower mean maximum airway pressures (38.9 +/- 10.1 cm H2O vs 64.6 +/- 15.4 cm H2O; p = 0.0001) and mean VT (0.79 +/- 0.11 L vs 1.05 +/- 0.15 L; p = 0.0002). No significant differences in mean airway pressure, end-expiratory pressure, FIO2, ventilator rate, arterial blood gas levels, and hemodynamic function were noted between APRV and CPPV. PMID- 1864121 TI - Effects of heart rate and pulmonary artery pressure on Doppler pulmonary artery acceleration time in experimental acute pulmonary hypertension. AB - Chronic pulmonary hypertension in humans is characterized by shortening of the pulmonary artery acceleration time as measured by Doppler echocardiography, such that the higher the pulmonary artery pressure, the shorter the pulmonary acceleration time. Increases in heart rate are also known to produce decreases in the pulmonary artery acceleration time. To explore the relationship between mean pulmonary artery pressure, heart rate, and Doppler pulmonary artery acceleration time, experimental acute pulmonary hypertension was created in nine Duroc swine, either by infusion of Sephadex beads with embolization of the pulmonary arterial circulation or by partially occluding the main pulmonary artery 8 to 10 cm distal to the pulmonic valve. Pulmonary artery Doppler flow velocity recordings and invasive pressure measurements were made at baseline and at paced atrial rates ranging from 60 to 160 beats per minute, in 20-beat increments. The results in this acute animal model reveal that increases in heart rate produced significant decreases in Doppler pulmonary artery acceleration time at mean pressures below 25 mm Hg. However, with mean pulmonary artery pressures greater than 25 mm Hg, both heart rate and increases in pulmonary artery pressure had no significant effect on acceleration time. PMID- 1864122 TI - Intraluminal pulsed Doppler evaluation of the pulmonary artery velocity time curve in a canine model of acute pulmonary hypertension. AB - The velocity pattern of the blood flow in the pulmonary artery was investigated in an animal model of acute pulmonary hypertension. Nine anesthetized, open-chest dogs were embolized with polystyrene microspheres, and the velocity pattern of the blood flow in the pulmonary artery was studied with use of an invasive pulsed Doppler technique. Phasic intraluminal velocity was recorded with use of a miniature piezoelectric crystal activated by 20-MHz Doppler pulses and mounted on the tip of a needle probe introduced into the pulmonary artery. The recorded Doppler quadrature signals were processed by spectral analysis. Significant increases occurred in mean, systolic, and diastolic pulmonary arterial pressures (p less than 0.0002), in pulmonary vascular resistance (p less than 0.005), and in negative velocity time (duration in milliseconds that the mean velocity was directed toward the pulmonic valve) (p less than 0.002). Significant decreases occurred in right ventricular ejection time (p less than 0.006) and in positive velocity time (duration in milliseconds that the mean velocity was directed away from the pulmonic valve) (p less than 0.005). A significant shortening in the time to peak velocity (acceleration time) was found (p less than 0.005). Second order regression analyses demonstrated an inverse correlation between the ratio of positive velocity time to negative velocity time and the mean pulmonary artery pressure in all animals (r = 0.71). These findings should be compared with the velocity patterns of the blood flow in the pulmonary artery obtained under pulmonary hypertensive conditions due to various causes to facilitate interpretation and understanding of clinical investigations. PMID- 1864123 TI - Thoracic and extrathoracic bronchial fistulas. PMID- 1864124 TI - Preventive pulmonary medical education. A review of its importance, status, and challenge. PMID- 1864125 TI - Inverse ratio ventilation in ARDS. Rationale and implementation. AB - Conventional ventilatory support of patients with the adult respiratory distress syndrome (ARDS) consists of volume-cycled ventilation with applied positive end expiratory pressure (PEEP). Unfortunately, recent evidence suggests that this strategy, as currently implemented, may perpetuate lung damage by overinflating and injuring distensible alveolar tissues. An alternative strategy--termed inverse ratio ventilation (IRV)--extends the inspiratory time, and, in concept, maintains or improves gas exchange at lower levels of PEEP and peak distending pressures. There are two methods to administer IRV: (1) volume-cycled ventilation with an end-inspiratory pause, or with a slow or decelerating inspiratory flow rate; or (2) pressure-controlled ventilation applied with a long inspiratory time. There are several real or theoretical problems common to both forms of IRV: excessive gas-trapping; adverse hemodynamic effects; and the need for sedation in most patients. Although there are many anecdotal reports of IRV, there are no controlled studies that compare outcome in ARDS patients treated with IRV as opposed to conventional ventilation. Nonetheless, clinicians are using IRV with increasing frequency. In the absence of well-designed clinical trials, we present interim guidelines for a ventilatory strategy in patients with ARDS based on the literature and our own clinical experience. PMID- 1864126 TI - Sudden apnea following attempted central line placement. PMID- 1864127 TI - An unusual cause of long-term interstitial pulmonary edema. PMID- 1864128 TI - The lung cancer dilemma. PMID- 1864129 TI - Lung cancer. Making the diagnosis. PMID- 1864130 TI - Lung cancer staging. PMID- 1864131 TI - Surgical techniques in the diagnosis of lung cancer. PMID- 1864132 TI - The International Clinical Respiratory Group. Report of the first meeting. PMID- 1864133 TI - Patient and ventilator work of breathing and ventilatory muscle loads at different levels of pressure support ventilation. PMID- 1864134 TI - Long-term oxygen therapy. PMID- 1864135 TI - Atypical myxoma. AB - We report the case of a 38-year-old woman with a large thin-walled cystic mass (6 x 5 x 4.5 cm) filled with arterial blood in the right atrium. The cystic mass with blood content was clearly delineated by transesophageal cross-sectional echocardiography and magnetic resonance imaging of the heart. At operation, a silver-whitish, smooth surfaced cystic mass was found attached to the free wall of the right atrium between the superior vena cava and the right atrial appendage with a broad base. Microscopically, the wall of the cyst was composed of stellate mesenchymal cells embedded within a myxoid matrix which was proved by alcian blue stain. To our knowledge, this type of cardiac myxoma has not been previously reported. PMID- 1864136 TI - Bronchiolitis obliterans organizing pneumonia in common variable immunodeficiency syndrome. AB - A 26-year-old woman with common variable immunodeficiency syndrome (CVID) associated with frequent episodes of pneumonia underwent an open lung biopsy showing bronchiolitis obliterans organizing pneumonia (BOOP). Following corticosteroid therapy, there were no further episodes of pneumonia. In addition, there was roentgenographic and gas exchange improvement. This is the first case of BOOP in association with CVID. An immunologic basis of BOOP is postulated. PMID- 1864137 TI - Localized Aspergillus infestation in primary lung carcinoma. Clinical and pathological contrasts with post-tuberculous intracavitary aspergilloma. AB - Saprophytic infestation with Aspergillus was observed in pathologic specimens of primary squamous cell lung carcinoma. In one case, the fungus grew in cystic scarred parenchyma and bronchi distal to an obstructing carcinoma of a segment bronchus. In the other, fungi colonized the inner surface of a peripheral cavitary carcinoma. Neither patient had roentgenographic evidence of aspergilloma and neither experienced severe pulmonary hemorrhage or other complications attributable to the presence of fungus. Although both specimens showed colonizing growth within the abnormal air spaces, in neither had the colonies detached to form a separate intracavitary fungus ball. These patients, and eight patients with similar lesions reported in the literature, demonstrate that Aspergillus colonization of a lung neoplasm frequently lacks one or both of the features characteristic of post-inflammatory intracavitary aspergilloma, a loose fungus ball and antifungal serum antibodies. No patient, to date, has developed massive hemorrhage as a complication of this lesion. PMID- 1864138 TI - Unusual diffuse pulmonary lymphatic proliferation in a young boy. AB - We describe a 4-year-old boy who died of an unusual generalized pulmonary lymphatic proliferation. His condition cannot clearly be categorized with any of the previously described pulmonary lymphatic disorders. PMID- 1864139 TI - Granulomatous pulmonary zygomycosis in a patient without underlying illness. Computed tomographic appearances and treatment by pneumonectomy. AB - Pulmonary zygomycosis rarely occurs in the absence of underlying disease. We report a patient with granulomatous pulmonary zygomycosis without underlying disease who presented with a pulmonary mass. We present the computed tomographic findings that we believe have not been described previously. We also report the successful treatment by pneumonectomy. PMID- 1864140 TI - Pulmonary mass and air meniscus sign in a 19-year-old man. AB - Sacrococcygeal teratoma is rarely diagnosed in adults. Pulmonary mass as the presenting clinical form of the malignant variety of this germ-cell tumor is exceptional. We report herein such a case with the noticeable peculiarity of showing the air meniscus sign on chest roentgenographic examination. PMID- 1864141 TI - Acute nonhemodynamic pulmonary edema with nifedipine in primary pulmonary hypertension. AB - A 34-year-old man with primary pulmonary hypertension developed acute nonhemodynamic pulmonary edema after a loading dose of nifedipine. Changes of the vascular permeability induced by the drug acting on the arteriolar wall of the capillary system could be an explanation. PMID- 1864142 TI - Fibrotic stage of allergic bronchopulmonary candidiasis. AB - Since its first description in 1952, ABPA has been recognized with increasing frequency. More recently fungi other than Aspergillus fumigatus, in particular Candida albicans, have been implicated in a similar disease process. The following case report illustrates the possibility of finding a fibrotic stage 5 ABPM caused by C albicans. PMID- 1864143 TI - Legionella pneumonia presenting as a bulging fissure on chest roentgenogram. AB - We report a case of Legionella pneumonia presenting as a bulging interlobar fissure on the lateral chest roentgenogram. This microorganism should be added to the list of etiologic agents producing a bulging fissure on chest roentgenogram. PMID- 1864144 TI - Group B streptococcal endocarditis of tricuspid valve. AB - We report three cases of group B streptococcal endocarditis of the tricuspid valve. Two patients were intravenous drug abusers. In the literature review, and including our cases, ten patients had group B streptococcal endocarditis of the tricuspid valve. Half of the patients were intravenous drug abusers. Four of the other patients had underlying conditions. All patients were treated with a penicillin with or without an aminoglycoside. Three patients underwent tricuspid valve surgery. The overall mortality was 20 percent. Both patients who died received medical therapy only. PMID- 1864145 TI - Myocardial infarction due to intracoronary thrombi without significant coronary artery disease in systemic lupus erythematosus. AB - Acute myocardial infarction is a potentially fatal complication of SLE. Reported mechanisms include atherosclerosis, arteritis and coronary arterial spasm. The following case report presents a fourth possible cause; intracoronary thrombus with angiographically normal coronary arteries in a patient with active lupus and AMI. PMID- 1864146 TI - Formation and spontaneous closure of an arteriovenous fistula after transvenous pacemaker placement. AB - We report the findings in a patient with the unusual complication of arteriovenous fistula formation of the subclavian vessels seven weeks following placement of a dual-chamber pacemaker. The fistula's subsequent course was equally unusual, closing spontaneously three weeks later. It is postulated that the thrombotic and fibrotic reaction elicited by the leads contributed to the fistula's closure. Two surgical procedures, correction of the fistula and reimplantation of the pacemaker, were thus avoided by careful monitoring of the patient. PMID- 1864147 TI - Left-sided pleural effusion secondary to splenic vein thrombosis. A previously unrecognized relationship. AB - The association of left-sided pleural effusion and subcapsular splenic hematoma was reported in 1980. We describe a patient in whom a left-sided pleural effusion resulted from splenic vein thrombosis, a relationship not previously reported. Splenectomy was performed, demonstrating the spleen to be enlarged and hemorrhagic. The pleural effusion did not recur after splenectomy. The three effusions due to splenic hematomas reported previously cleared only after splenectomy, suggesting splenectomy may be necessary to prevent reaccumulation. We propose possible pathophysiologic mechanisms and recommend that splenic vein thrombosis be considered in the differential diagnosis of unexplained left-sided pleural effusions. PMID- 1864148 TI - Transthoracic and transesophageal echocardiography in the diagnosis and surgical management of right atrial myxoma. AB - An asymptomatic patient was discovered to have a large right atrial myxoma by transthoracic echocardiography. Preoperative considerations included the possibility of satellite lesions, left atrial origin, and a question of tricuspid valve involvement. Subsequent operative transesophageal echocardiography demonstrated single-stalk attachment in the right atrial septal wall and no satellite lesions. Doppler and color flow examination immediately following tumor removal aided in the decision not to perform tricuspid annuloplasty as there was no significant tricuspid regurgitation. The combined use of transthoracic and transesophageal echocardiography with Doppler and color flow imaging aids in the preoperative and intraoperative diagnosis and surgical management of right atrial tumors. PMID- 1864149 TI - Familial multiple bilateral pneumothorax associated with Marfan syndrome. AB - Three members of one family, a father and two sons, inflicted with Marfan syndrome, suffered multiple bilateral episodes of spontaneous pneumothorax that required repeated drainage procedures. The youngest patient also had an episode of unilateral expansion pulmonary edema; he underwent sequential pleural abrasions. Familial pneumothorax is very uncommon, and its association with Marfan syndrome is an exception. PMID- 1864150 TI - Closure of a tracheoesophageal fistula by bronchoscopic application of fibrin glue and decontamination of the oral cavity. AB - A tracheoesophageal fistula was successfully closed with a fibrin adhesive applied by means of a fiberoptic bronchoscope, instead of by esophagoscopy. To facilitate closure of the fistula, the technique was combined with decontamination of the oral cavity, to avoid bacterial contamination. The procedure is proposed as an alternative to surgery for critically ill patients. PMID- 1864151 TI - Noninvasive methods in the diagnosis of ruptured aneurysm of Valsalva. Usefulness of magnetic resonance imaging and Doppler echocardiography. AB - A ruptured aneurysm of noncoronary sinus of Valsalva was diagnosed noninvasively by magnetic resonance imaging (MRI), as well as by Doppler echocardiography. Diagnosis of this disease by MRI has not been reported previously. PMID- 1864152 TI - Balloon dilation of postsurgical subaortic obstruction. AB - Two children aged 10 and 5.5 years underwent balloon dilation for postsurgical subaortic obstruction. The outcome and the role of this procedure are discussed. PMID- 1864153 TI - Pulmonary function tests in bronchopleural fistula. AB - A 53-year-old white man underwent a left pneumonectomy for alveolar cell carcinoma. His postoperative course was complicated by pneumonia. At a follow-up clinic visit, the patient complained of a "roaring sound" during respiration. A follow-up PFT did not show the expected loss of volume (nitrogen washout) from a preoperative PFT, suggesting a bronchopleural fistula. A chest x-ray film and xenon lung scan confirmed the diagnosis. The fistula was surgically repaired. PMID- 1864154 TI - Plasmapheresis in a case of eosinophilia-myalgia syndrome with ascending polyneuropathy. AB - Eosinophilia-myalgia syndrome complicated by ascending polyneuropathy in a 40 year-old woman is described. High-dose intravenous steroids had no beneficial effect on the clinical course. Dramatic and rapid clinical improvement occurred with the use of plasmapheresis. The use of this therapeutic modality should be considered in patients with a similar clinical presentation. PMID- 1864155 TI - Airflow obstruction and roadside breath alcohol testing. PMID- 1864156 TI - Tuberculosis and human immunodeficiency virus infection in Italy. Preliminary results from a multicenter study. PMID- 1864157 TI - Synchronous pulmonary and renal cancer. PMID- 1864158 TI - Tropical pulmonary eosinophilia. PMID- 1864159 TI - Bi-PAP, nasal ventilation, and body ventilators. PMID- 1864160 TI - Need for oxygen consumption measurements. PMID- 1864161 TI - Use of the APACHE II system in surgical lung carcinoma patients. PMID- 1864162 TI - Salmonella lung abscess in a patient with acquired immunodeficiency syndrome. PMID- 1864163 TI - Lung needle aspiration for diagnosis of pneumonia. PMID- 1864164 TI - Inhalation of a mercury thermometer. PMID- 1864166 TI - [The "D.E.A." in dentistry]. PMID- 1864165 TI - [Osseointegration in complete fixed dentures: from fundamentals to clinical application]. PMID- 1864167 TI - [New classification of edentulous jaw ridges in man]. PMID- 1864168 TI - [In vitro demonstration of polymerization retraction of composites by capillary penetration phenomenon]. PMID- 1864169 TI - [Staphylococci and necrotizing ulcerative gingivitis. (Apropos of 11 clinical cases)]. PMID- 1864170 TI - [Autologous bone marrow transplantation for acute leukemia]. PMID- 1864171 TI - [Effect of low protein diet, plus essential amino acids on lipid metabolism in patients with chronic renal failure]. AB - We investigated lipoprotein profile of 18 non-dialysis patients with CRF and 17 patients on hemodialysis, and studied effect of LPD plus EAA on lipid metabolism of 18 non-dialysis patients with CRF. The results revealed that total triglyceride, cholesterol, LDL, VLDL, and semi-quantity of ApoCII, ApoCIII were significantly increased, and HDL, ApoAI ApoAI/ApoB rate, semiquantify of ApoCI were significantly reduced in non-dialysis patients and patients on hemodialysis; VLDL and Ccr were closely negative related in non-dialysis patients. The lipid abnormalities were more severe in non-dialysis patients complicated with hypertension than without hypertension. After 6 to 10 weeks' LPD plus EAA treatment in 18 non-dialysis patients, total triglyceride, cholesterol, LDL, VLDL were significantly reduced, and HDL, ApoAI, ApoAI/ApoB were significantly increased. We conclude that it is characterized by type IV hyperlipidemia in lipid abnormalities of patients with CRF, and LPD plus EAA treatment may improve it effectively. PMID- 1864172 TI - [Influence of hemoultrafiltration and hemodialysis on endothelin]. AB - In order to study the mechanism of plasma ET increment in CRF patients, we investigated 20 endothelin (CRF) patients undergone hemoultrafiltration for 90 min followed by hemodialysis, and 12 patients subjected to single hemodialysis. The results revealed that 90 min's ultrafiltration along with 2500 ml fluid extraction brought about a significant decrease in plasma ET (from 1132 to 753 pg/ml, P less than 0.05), while the hemodialysis without water extraction of a same period resulted no significant change. In the meantime, the BUN in the ultrafiltration group showed no prominent change. But the hemodialysis group presented a significant decrease (from 34.6 to 22.5 mmol/L P less than 0.05), which showed that the ET falling had no significant relevance to the metabolic products extraction. In the followed 120 min's hemodialysis, ET level in the two groups decreased in a different extend. Therefore, the research suggested that decreased extracellular volume via ultrafiltration can lead to the discretion of ET level. PMID- 1864173 TI - [Urinary Tamm-Horsfall protein coating of free cells and its clinical diagnostic significance]. AB - The origin of free cells in urine is difficult to determine in the absence of cellular casts. Using fluorescein-conjugated antibody to human Tamm-Horsfall protein (THP), it examines THP coating of free cells in urine (THP-CFC), that could be distinguished between renal parenchymal disease (RPD) and lower urinary tract disease (LUTD). We had examined THP-CFC in urine of the patients with all kinds of RPD, renal or ureteral stone (RUS) and LUTD. The percentage of THP-CFCs was 0% in healthy volunteers (n = 34), 0-8% in LUTD group (n = 14), 86.3% in glomerulonephritis and SLE nephritis group (n = 29), 80.8% in chronic intertitial nephritis group (n = 26), 0-10% in RUS group (n = 14). The research results suggest that the percentage of THP-CFCs between the RPD and LUTD or RUS had a significant difference. The presence of THP-CFC in RPD and its absence in LUTD suggests that this simple test may be of use in differentiating RPD from LUTD. PMID- 1864174 TI - [Study of lipid peroxidation in patients with chronic renal failure]. AB - The levels of lipid peroxide in plasma and erythrocyte membrane, the contents of blood superoxide dismutase and copper, zinc, iron in plasma, and erythrocyte membrane fluidity were investigated in patients with chronic renal failure (CRF). In comparison with the health subjects the levels of lipid peroxide in plasma and erythrocyte membrane were significantly higher, the contents of blood superoxide dismutase were significantly lower in the patients with CRF. The plasma copper increased and plasma zinc decreased, but plasma iron remained unchanges in the patients of CRF. We found that rises of lipid peroxide in erythrocyte membrane were closely related to changes of microviscosity in them. PMID- 1864175 TI - [Prognostic factors and treatment of severe acute pancreatitis]. AB - Seventy two cases of severe acute pancreatitis (SAP) all documented by laparotomy. Fifteen were found to be of edematous and 58 of hemorrhagic and necrotic type, 29 cases died (39.7%). The following 6 items are of prognostic importance in both the survival and the dead groups: (1) Shock, (2) Serum albumin less than 30 g/L. (3) BUN greater than 7 mmol/L, (4) Blood glucose greater than 11.1 mmol/L, (5) Abnormal urine analysis, (6) PaO2 less than 8.6 kPa. Thirty two cases showed positivity of 3 or more of the 6 items, among them 21 died (65.6%). Fourty one cases had 2 or less positive items and 8 (19.5%) died. The mortality rate was not significantly different between the group who had either the edematous or the hemorrhagic necrotizing varieties. It was found that 88.2% of the patients in the dead group had hemorrhagic and necrotizing variety in the peripancreatic and similar pathology appeared in the survival group only in 50% (P less than 0.05). The risk was markedly increased in these patients with systemic complication in the lungs, kidney and brain. We found no effect of vasodilatation drugs (salvia miltiorrhiza and anisodamine) in the treatment of SAP. PMID- 1864176 TI - [99mTc-CPI myocardial perfusion tomography for evaluation of coronary artery disease]. AB - Stress 99mTc-carbomethoxy isopropyl isonitrile myocardial perfusion tomography (Tc-CPI MPT) was performed in 24 controls with normal coronary arteriograms or stenosis less than 50% and 30 patients with coronary artery disease (CAD) (stenosis greater than 50%). The sensitivity and specificity for the detection of CAD with Tc-CPI MPI was 90% and 96% respectively. The sens by Tc-CPI MPI was 89% for the patients with one-vessel involvement, 88% for two-vessel involvement, 100% for three-vessel involvement. The sens for the detection of LAD, LCX and RCA involvement was 86%, 86% and 80% respectively. The spec were 100%, 100% and 91% respectively. It is concluded that TC-CPI MPT is a valuable technique for diagnosing CAD. PMID- 1864177 TI - [The prehospital emergency cardiac care in patients with acute myocardial infarction]. AB - In order to evaluate the current status of prehospital care of acute myocardial infarction (AMI) in this city, the clinical manifestations and the emergency cardiac care in prehospital phase in 210 patients were reviewed in the period from 1987 to 1988. Before admission to CCU, 45.7% of the patients had complications of severe cardiac arrhythmias or hemodynamic disturbances and 14.8% had cardiac arrests. The mortality during the first 4 weeks was 25.2%. Among 53 patients who died, 50.9% occurred before admission and 37.7% within 1 hour. One hundred and ten patients (52.4%) had prehospital care and, 4 of them provided by the City Emergency Center and others by the local clinics near by. The median time from the cardiac attack to the first medical care, hospital arrival and CCU admission was 2, 3.6 and 6.3 hours respectively. The management on the scene was not efficient and effective in many patients. The rate of successful resuscitation in patients who had cardiac arrest out of hospital was only 7.7%. We are impressed that the mortality of patients with AMI is mainly in the early stage after appearance of symptoms. The initiation of emergency cardiac care is very necessary. The current status of prehospital cardiac care needs to be improved immediately, some suggestions are made for this purpose. PMID- 1864178 TI - [Changes of thromboxane A2 (TXA2) and prostacyclin (PGI2) in COPD patients with pulmonary hypertension]. AB - We measured the pulmonary arterial pressure and the level of Thromboxane A2 (TXA2), and Prostacyclin (PGI2) in 30 stable COPD patients and the level of TXA2 and PGI2 in 10 normal subjects so as to investigate the changes of TXA2 and PGI2 in COPD patients with pulmonary hypertension. The results showed that the level of TXA2 increased significantly in COPD patients with dominant and latent pulmonary hypertension when compared with that in normal subjects (P less than 0.001, less than 0.01), and the level of TXA2 in COPD patients with dominant pulmonary hypertension was also higher than that in COPD patients with latent pulmonary hypertension (P less than 0.02), but there was no difference in the level of PGI2 among normal subjects and COPD patients with or without pulmonary hypertension. This indicates that TXA2 plays an important role in causing pulmonary hypertension in COPD patients. PMID- 1864179 TI - [Hepatic inflammatory pseudotumor. A report of 5 cases]. AB - Hepatic inflammatory pseudotumor (HIP) is rare. To our knowledge, there have only been 27 cases reported since 1953. We studied additional five cases, male, aged 13-56 years, with a history of the disease of 20 days-1 year. Major complains were epigastric pain, fever of unknown causes, and epigastric mass. All five HIPs were solitary and surgically resected with a final diagnosis made pathologically. HIPs mimic the characters of liver cancer on ultrasonography and CT scanning, however, the following several points could be used to establish the diagnosis: patients with a long history of hepatic tumor still in a rather good condition; patients with no cirrhosis and negative AFP test results; tumors that are well encapsulated, etc. Surgical exploration should be attempted in all patients unless in those with poor risks in which steroid therapy may prove useful. PMID- 1864180 TI - [Acute hemorrhagic necrotic pancreatitis: clinical pathology and long-term results of surgical treatment]. AB - There have been no generally accepted criteria for the clinicopathological classification of acute hemorrhagic necrotic pancreatitis (AHNP). We based on our experience in the surgical treatment of 30 patients with proved AHNP and their long-term follow up results, divided AHNP into two types, i.e. sporadic focal and extensive fusional, each having its own distinctive gross pathological features. The mortality rate of sporadic type was much lower than that of extensive fusional type. Eighteen patients with AHNP who survived the initial stormy clinical course were followed up and their pancreatic juice was collected endoscopically for exocrine examination. It was found that the exocrine function was pretty much intact in spite of its evident damage in image. PMID- 1864181 TI - [Closed marsupialization and delayed marsupialization in the treatment of severe pancreatitis]. AB - The timing for surgical intervention and the type of operation in the treatment of severe pancreatitis are still controversial. In this study, we used closed marsupialization in which early operation was preferable and after decompression of the pancreas and necrosectomy, both edges of the opened greater omentum were sutured respectively to the upper and lower peritoneal borders of the transverse abdominal incision, forming a marsupium separating the greater and lesser abdominal cavities from each other. The abdominal incision was then sutured to close the opening of the marsupium. Should clinical features or CT, BUS scan have indicated the existence of pancreatic abscess a week or longer after the exploration, stiches of the abdominal wall incision were removed. The marsupium was easily reentered and necrotic tissue removed. As the omentum edges were adhered to the abdominal wall incision separating the greater and lesser abdominal cavities, reoperation was safe. The incision was then kept open (delayed marsupialization). The theoretical basis of the operation and satisfactory clinical results are discussed. PMID- 1864182 TI - [Valvuloplasty and fixation of the femoral vein for valvular incompetence of deep veins of the lower extremity]. AB - Fifty cases (54 limbs) of valvuloplasty and fixation of the incompetent valve of the femoral vein were reported. Diagnosis was made by clinical features, measurement of ambulatory venous pressure, ascending and descending phlebography, and by intraoperative checking the blood flow. After repairing the highest primary valve of the superficial femoral vein a circular suture around the vein at 2 mm under the repaired valve was made to prevent the recurrence of valvular incompetence. Patients were followed-up for 6 to 45 months (mean 20.2 months) with satisfactory results in all and excellent in 50 limbs (92.6%). The swelling subsided, stasis dermatitis and ulcer healed promptly, the "heavy leg" became light, and venous pressure of post-exercise lowered significantly (P less than 0.01). No retrograde flow of contrast medium was detected during the descending phlebography after operation. The results suggest that this operation is better than simple repair of the incompetent valve. PMID- 1864183 TI - [Diagnosis of deep venous thrombosis of the lower limb by Doppler ultrasound technique]. AB - In this study, eighty limbs (71 patients) with clinically suspected deep venous thrombosis (DVT) were investigated by both venography and Doppler ultrasonography. Diagnosis was confirmed by venography in 67 limbs and Doppler ultrasonography was positive in 66 of them with the Doppler sensitivity of 98%. In the remaining 13 limbs clinically suspected to have DVT, neither venography nor Doppler ultrasonography found any abnormality in the venous system of the lower limbs. PMID- 1864184 TI - [Avulsion damage of penile and scrotal skin]. AB - Five cases of severe avulsion damage of penile and scrotal skin were treated from 1978 to 1988. One case was complicated by disruption of arteria and vena iliaca externa, 2 cases were complicated by rupture of testes and 2 cases by pelvic fracture and urethral damage. Three cases were cured by utilizing femoral island flap. In the other 2 cases treated with debridement, the damaged skin appeared necrotic postoperatively and satisfactory results were achieved by utilizing a mid-thick stamp-shaped flap technique. All the 5 cases were followed up for 1-10 years and normal sexual function and fertility were restored. PMID- 1864186 TI - [In vitro nucleation factors--mucus glycoprotein and proteins: changes and mechanisms in the process of sludge and gallstone formation]. AB - Both mucus glycoprotein (MGP) and proteins are in vitro nucleation factors. Biliary sludge proved to be a precursor of gallstones. In this study, the MGP in gallbladder bile (GB) and the RNA content of the membrane-bound polyribosome in gallbladder epithelium were significantly higher in the sludge group than that in gallstone and control group. These facts demonstrated the increased synthesis and secretion of glycoproteins in the prestone stage. The RNA content of free polyribosome in the sludge group was also significantly greater than that in the control group so that in prestone stage there was an increase of cell proliferation in the gallbladder epithelium. Patients with sludge and cholesterol gallstones had significantly higher protein concentrations in GB than those without gallstones or with pigment stones. The gallbladder-hepatic bile ratio of proteins was significantly less than that of cholesterol, and there was a highly positive correlation between glycoproteins and proteins in GB. Therefore, the only reasonable explanation for the higher protein content in these two kinds of patients was that the mucus selectively inhibited protein absorption in the gallbladder. The increases in MGP and protein content in GB during the embryonic stage of gallstones might play a significant role in the formation of both cholesterol and pigment gallstones. PMID- 1864185 TI - [Therapeutic effect of hyperbaric oxygen on recovery of surgically repaired peripheral nerve injury]. AB - 114 patients with peripheral nerve injury were treated microsurgically. 54 patients with 65 nerve injuries were given hyperbaric oxygen as supplementary treatment. The excellent and good results of the 65 nerves accounted for 89.2%, but of those nerves in patients not treated with hyperbaric oxygen for 73.2% (P less than 0.05). The result was better in the hyperbaric oxygen group regardless of the repairing method used, particularly in those nerve grafting had been done (24.9, P less than 0.05). As for the time lapsed from injury to surgery. The results of fresh injuries showed no difference in either group, but hyperbaric oxygen was of much benefit to the old cases: the longer the delay the greater in difference between different groups, but better results were obtained in the hyperbaric oxygen group. The early the operation the better the result in either group. PMID- 1864187 TI - [Effect of discectomy on the stress distribution in lumbar spine]. AB - The change of stress distribution of lumbar spine after discectomy was analysed with three-dimensional finite element method. It was showed that the stress level in posterior element was elevated, but the stress level in anterior element was lower than before. The most significant change of stress distribution was found in trabecular bone of vertebral bodies. The clinical relevance was discussed. PMID- 1864189 TI - [Transposition of the dorsal fascio-cutaneous flap of foot in treatment of talipes equinovarus]. AB - For the purpose of one stage correction of severe congenital Talipes equinovarus, a new technique was designed to fashion a fascio-cutaneous flap from the redundant tissue on dorsolateral area of the foot, and it is then transposed to cover the defect left on the posteromedial part of the same foot following complete releasing and correcting the contractured soft tissue and lengthening the shortened tendons. This newly designed method was applied to 26 feet of severe congenital talipes equino-varus in 16 children aged 3/4-4 years. The foot deformity has been beautifully corrected and the transposed flap soundly healed in every foot without complication of any kind. The surgical procedures are fully described in the paper. PMID- 1864188 TI - [Determination of multiple chemical elements in CSF in Parkinson disease after intracerebral autotransplantation of the adrenal medulla]. AB - The contents of indispensable major elements sodium (Na), phosphorus (P), calcium (Ca), magnesium (Mg), trace elements iron (Fe), copper (Cu), nickel (Ni), zinc (Zn), strontium (Sr), vanadium (V), chromium (Cr), manganese (Mn), molybdenum (Mo), and other elements lead (Pb), silicon (Si), aluminium (Al), titanium (Ti), barium (Ba), lanthanum (La), cadmium (Yb), cerium (Ce), scandium (Sc), silver (Ag), in cerebrospinal fluid (CSF) were measured in 13 patients suffering from Parkinson disease before and after autotransplantation of adrenal medulla. It was found that while the patients' objective symptoms were relieved and the contents of monoamine transmitters were changed, the contents of P, V, Co, Cr, in CSF increased significantly (P less than 0.05 or 0.01) at the first, 2nd, 4th, 6th, and 8th week, the contents of Mn in CSF also increased significantly at the first 4th week (P less than 0.05) but decreased significantly at the 8th week the contents of Zn in CSF increased significantly (P less than 0.05) at the 2nd week; Mo increased significantly (P less than 0.05 or 0.01) at the 4th and 8th week B increased significantly (P less than 0.05) at the first week; the contents of Ca, Na, Sr, Ba, Al, Ti, La, Ce, Yb, Sc, Ag in CSF increased significantly (P less than 0.05 or 0.01) at the 8th week, Mg, Fe, Cu Ni, Pb, Si, Cd remained unchanged after operation. The results suggest that the contents of these chemical elements can be affected by this kind of operation, indicating that these elements are involved in the pathogenesis of Parkinsonism. PMID- 1864190 TI - [Bladder flap urethroplasty for vesicovaginal fistula with urethral loss]. AB - A new operative method termed bladder flap urethroplasty is presented in this article. With this method, a patient with traumatic vesicovaginal fistula and urethral loss was treated successfully. Postoperative follow-up for 1.5 years showed that the patient could have normal micturition with a satisfactory sphincteric function. The authors believe that the procedure is a relatively ideal method for the treatment of severe vesicovaginal fistula. PMID- 1864191 TI - [The criteria for the evaluation of impairment hand function]. PMID- 1864192 TI - Diffuse esophageal spasm. A rare motility disorder not characterized by high amplitude contractions. AB - Diffuse esophageal spasm (DES) has frequently been described as a motility disorder characterized by simultaneous, high-amplitude contractions. We reviewed the results of esophageal manometry testing on a total of 1480 patients referred to our lab over 36 months. Lower esophageal sphincter (LES) pressure was determined by a mean of four station pull-through. Esophageal body motility was assessed following 10 wet swallows. In our lab a diagnosis of DES is made when greater than 10% but less than 100% of contractions are simultaneous. Manometric findings of DES were rare, with an overall prevalence of 4% (56/1480). Of the 56 patients with a manometric diagnosis of DES, high-amplitude (mean greater than or equal to 180 mm Hg) peristaltic contractions were found in only two (4%). No simultaneous contractions with amplitude greater than or equal to 180 mm Hg were seen. Pressures of simultaneous contractions were consistently lower than peristaltic contractions. A hypertensive LES pressure (greater than or equal to 45 mm Hg) was present in 5/56 DES patients (9%). Poor LES relaxation was found in 7/56 DES patients (13%). We conclude that DES is a rare manometric finding, regardless of the reason for referral, and that the occurrence of high-amplitude contractions in DES is equally rare. PMID- 1864193 TI - Transcutaneous electrical nerve stimulation decreases lower esophageal sphincter pressure in patients with achalasia. AB - Vasoactive intestinal peptide (VIP) is believed to be an inhibitory neurotransmitter responsible for lower esophageal sphincter (LES) relaxation. In patients with achalasia the concentration of VIP and the number of VIP-containing nerve fibers are reduced or absent. It has been suggested that the response to low-frequency transcutaneous electrical nerve stimulation (TENS) may be mediated by a nonadrenergic noncholinergic pathway in which the release of VIP is responsible for the smooth muscle relaxation. The present study was designed to evaluate the effect of TENS on LES pressure and on VIP plasma concentrations in six patients with achalasia (five female, one male). TENS was performed daily during one week for 45-min sessions with a pocket stimulator that delivered low frequency pulses (6.5 Hz), at 10 pulses/sec of 0.1-msec duration at intensities of 10-20 mA until rhythmic flexion of the fingers was obtained without producing pain. LES pressure and VIP levels were obtained before TENS, after the first 45 min session, and after a week of daily stimulation. After 45-min, TENS produced a significant reduction (P less than 0.01) in LES resting pressure from the mean value 56 +/- 6.4 mm Hg to 42.3 +/- 6.4 mm Hg; with LES relaxation improvement from 50.6 +/- 3% to 63.1 +/- 3.2% (P less than 0.01). After one week of daily TENS, an additional reduction in LES resting pressure (40.3 +/- 4 mm Hg) was observed (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864194 TI - Provocation of transient lower esophageal sphincter relaxations by meals in patients with symptomatic gastroesophageal reflux. AB - The effect of a meal on the rate of transient lower esophageal sphincter (LES) relaxations and patterns of gastroesophageal reflux was investigated in 49 patients referred for evaluation of gastroesophageal reflux. Esophageal motility and pH were recorded concurrently before and after a standard meal. In the patients with symptomatic reflux, the meal induced a four- to sevenfold increase in the gastroesophageal reflux through two mechanisms: a four- to fivefold increase in the rate of transient LES relaxations and an increase in the proportion of transient LES relaxations accompanied by reflux from 47% to 68%. Overall the rate of reflux episodes that occurred by mechanisms other than transient LES relaxation did not increase significantly. An exception to these findings were those in six patients with chronically absent basal LES pressure in whom transient LES relaxations could not be scored. In these patients, reflux increased postprandially through mechanisms other than transient LES relaxation. These findings confirm the pivotal importance of transient LES relaxations in the pathogenesis of gastroesophageal reflux. PMID- 1864195 TI - Clinical correlates of abnormal sensitivity to intraesophageal balloon distension. AB - Sixty-five patients with esophageal complaints were studied to determine clinical associations with abnormal sensitivity to intraesophageal balloon distension (esophageal sensory dysfunction). Associations were examined in four categories: motility, esophageal symptoms, recent psychological symptoms, and general clinical features. A positive response to balloon distension (pain with less than or equal to 8 ml volume) was found in 29 (45%) of the subjects. This response was associated with specific findings in each category except recent psychological symptoms. A multiple logistic regression analysis indicated that an increased frequency of multipeaked waves on motility testing, presence of dysphagia, and shorter height of the subject each had an independent association with positive response to balloon distension (P less than or equal to 0.05 for each). Further comparison of subjects with sensory dysfunction, motor dysfunction, or both (sensorimotor dysfunction) indicated that subjects with the combined disorder appeared more symptomatic than those with either finding alone. These observations indicate that: (1) esophageal motor and sensory dysfunction are partially associated, but both contribute to the symptomatic state; (2) dysphagia may be representative of sensory dysfunction in some cases; and (3) subject height should be taken into consideration when interpreting balloon distension results. PMID- 1864196 TI - The effect of intravenous diazepam on esophageal motility in normal subjects. AB - Controversy exists over whether diazepam can be used for sedation during esophageal manometry studies without affecting the results. To evaluate the effect of diazepam, 20 healthy asymptomatic volunteers were studied using a standard manometry protocol employing an Arndorfer capillary infusion system. Following a baseline manometry, each subject received 0.1 mg/kg diazepam intravenously over 1 min and underwent repeat manometry 5 min after completion of the injection. All manometry recordings were coded and read blindly. The amplitude of the lower esophageal sphincter was significantly reduced by diazepam from 26.2 +/- 10.9 and 30.0 +/- 10.9 mm Hg to 18.8 +/- 7.6 and 24.5 +/- 9.7 mm Hg by rapid and station pull-through methods, respectively (P less than 0.01 both methods). Esophageal contraction wave duration was significantly increased following diazepam at 3, 8, and 13 cm above the lower esophageal sphincter (P less than 0.01 all levels). There was a trend toward increased contraction wave amplitude following diazepam administration in the lower three fourths of the esophagus. On the basis of these results, we conclude that diazepam sedation may produce misleading results when used during esophageal manometric testing. It is recommended that diazepam not be used in manometric studies of normal subjects or patients with reflux esophagitis and that manometric findings in patients with hypertensive or spastic disorders be interpreted with caution if diazepam is given as a premedication. PMID- 1864197 TI - A time-dependent study of passive esophageal wall properties and collagen content in rabbits with esophageal varices. AB - The passive biomechanical wall properties of the esophagus were studied in rabbits with esophageal varices and controls using a four-electrode impedance technique. Stepwise pressure inflation and deflation was done for analysis of esophageal cross-sectional area, compliance, and hysteresis monthly during six months. At sacrifice, the esophageal collagen content was determined. A small but statistically insignificant increase in compliance was observed during the six month observation period in both groups. No differences were observed between the groups (P greater than 0.3). No change in hysteresis was observed in either group. The group with esophageal varices had significantly higher collagen content in the distal esophagus when compared to controls (P less than 0.05). No difference was demonstrated in the proximal part. No correlation was demonstrated between the collagen content and esophageal compliance. The study demonstrated that the method allows measurement of luminal cross-sectional area and tissue elasticity. No relationship was found, however, between the collagen content and compliance of the rabbit esophagus. PMID- 1864199 TI - Surgery or chemoneurolysis for complete vagal denervation of rat stomach? AB - This study compared the completeness of vagal denervation of the rat stomach by transection vagotomy to that by chemoneurolysis (30% ethyl alcohol) alone or supplemented by truncal vagotomy. The H+ output over 6 hr with vagotomy by chemoneurolysis (10.5 +/- 0.7 mumol, mean +/- SEM, N = 10) or truncal vagotomy and chemoneurolysis (10.9 +/- 1.1 mumol, mean +/- SEM, N = 10) was similar to that with transection vagotomy, but significantly (P less than 0.01) lower than that with truncal vagotomy by chemoneurolysis (17.9 +/- 1.1 mumol, N = 10). The latter output was similar to that of truncal vagotomy performed surgically (18.2 +/- 1.3 mumol, N = 10). Reserpine (0.1 mg/kg intraperitoneal) stimulated gastric acid secretion relative to control values (207 +/- 3.1 mumol vs 67 +/- 3.2 mumol, N = 10, P less than 0.001) and transection vagotomy, vagotomy by chemoneurolysis, or truncal vagotomy and chemoneurolysis were more effective (P less than 0.01) than truncal vagotomy performed surgically or by chemoneurolysis in preventing this stimulation. Insulin stimulated the H+ output (184 +/- 2.9 mumol vs 62 +/- 3.1 mumol, N = 10, P less than 0.001) and transection vagotomy, vagotomy by chemoneurolysis, or truncal vagotomy and chemoneurolysis were more effective (P less than 0.01) than truncal vagotomy done surgically or by chemoneurolysis in preventing this action. These results were reproducible in experiments done after three months. This investigation shows that transection vagotomy, vagotomy by chemoneurolysis, and truncal vagotomy plus chemoneurolysis are equally effective in achieving vagal denervation of the rat stomach and are superior in this respect to truncal vagotomy done surgically or by chemoneurolysis. PMID- 1864198 TI - Abnormalities of gastrointestinal motility in children with nonulcer dyspepsia and in children with gastroesophageal reflux disease. AB - In 11 children (mean age 44.2 months) with symptoms suggesting upper intestinal dysfunction (nonulcer dyspepsia), in nine children (mean age 27.3 months) with gastroesophageal reflux (GER) disease, and in seven controls (mean age 20.4 months) we investigated fasting [for 3 hr or until two migrating motor complexes (MMC) were observed] and fed (90 min) antroduodenal motility by means of perfused catheter system; furthermore, we measured both gastric emptying of a radiolabeled milk formula and fasting duodenogastric reflux during manometry by assessing bile salt concentration in gastric aspirates. No structural abnormalities of gastrointestinal tract and organic disorders were detected in the patients. In a high proportion of both groups of patients we found manometric abnormalities of interdigestive and fed motor patterns that were not seen in the controls: absence of antral phase III of MMC; significant decrease of antral and/or duodenal motor activity during fasting and/or fed periods; abnormal propagation or configuration of MMC phase III that was significantly shorter than in controls; bursts of sustained fasting and/or fed phasic duodenal activity, frequently uncoordinated with adjacent gut segments. When compared to controls, the mean intragastric concentration of bile salts during all MMC phases and the mean 1-hr percent gastric activity of the radiolabeled milk were significantly higher in the two groups of patients. We conclude that in a high proportion of children with nonulcer dyspepsia and of children with GER disease, gastrointestinal manometry may reveal significant irregularities of antral and duodenal motility, which are associated with increased duodenogastric reflux and delayed gastric emptying. PMID- 1864200 TI - Lymphocytic gastritis in nonulcer dyspepsia. AB - The prevalence of lymphocytic gastritis, a specific form of chronic gastritis characterized by infiltration of gastric superficial epithelium with T lymphocytes, has been established in nonulcer dyspepsia. Among a population sample of 586 patients at risk for gastric carcinoma, 0.83% of patients with nonulcer dyspepsia and 1.63% of patients with chronic active gastritis showed lymphocytic gastritis. Among routine gastric biopsies from 5130 patients, only five cases met histological and immunohistochemical criteria of lymphocytic gastritis. PMID- 1864201 TI - Seroepidemiology of Helicobacter pylori infection in India. Comparison of developing and developed countries. AB - Helicobacter pylori (previously Campylobacter pylori) is now accepted as the major cause of type B gastritis and thus what is known about the epidemiology of type B gastritis can reasonably be transferred to H. pylori. We used a specific ELISA for anti-H. pylori IgG to study the prevalence of H. pylori infection in a population of lower socioeconomic class from Hyderabad, India. The results from India were compared to studies from other parts of the world. Two hundred thirty eight individuals ages 3 to 70 participated. The frequency of H. pylori infection increased with age (P less than 0.01) and was greater than 80% by age 20. H. pylori infection was present in 79% of the population studied; there was no gender-related difference in prevalence of H. pylori infection. IgG antibody against hepatitis A (HAV) was rapidly acquired in Hyderabad; in a subset of 58 children between the ages of 3 and 21 tested, the frequency of anti-HAV was 98.2%. The prevalence of H. pylori infection increases with age in both developed and developing countries. The high age-specific prevalence of H. pylori infection in developing countries is probably a reflection of the lower socioeconomic level of those areas. PMID- 1864202 TI - Severity of Helicobacter-induced gastric injury correlates with gastric juice ammonia. AB - We postulated that ammonia produced by Helicobacter pylori may contribute to gastric mucosal injury. This hypothesis was evaluated in Helicobacter-positive patients with chronic renal failure in whom a high urea concentration might amplify this phenomenon. Gastric urea and ammonia were measured, and the severity of gastritis was evaluated by counting mononuclear and polymorphonuclear cells. High gastric ammonia and low urea in Helicobacter-positive patients, and the converse in Helicobacter-negative subjects, were observed. There was a significant correlation between gastric ammonia and interstitial polymorphonuclear leukocytes infiltration (P less than 0.05), suggesting a causal link. Eradication of Helicobacter pylori was associated with a decrease of ammonia and an increase of urea (P less than 0.01). The significant correlation between the severity of gastric inflammation and the gastric juice ammonia concentration suggests that ammonia may play a pathogenic role in Helicobacter associated gastric injury. PMID- 1864203 TI - Combined treatment of symptomatic gallbladder stones by extracorporeal shock-wave lithotripsy (ESWL) and instillation of methyl tert-butyl ether (MTBE). AB - Twenty-four patients with symptomatic gallbladder stones (12 radiolucent and 12 calcified) were treated by a combined approach of extracorporeal shock-wave lithotripsy (ESWL) and subsequent instillation of methyl tert-butyl ether (MTBE). The patients received a mean of 1500 +/- 185 shock-wave discharges. The mean instillation time of MTBE was 13 +/- 4.2 hr. Treatment was tolerated without major adverse effects. Within a time period of three to five days eight of 12 patients with pure radiolucent stones and four of 12 with calcified stones became stone-free. After a median follow-up of five months (range: one week to 26 months), a total of 11 patients (92%) with radiolucent stones and of eight patients (66%) of those with calcified stones were free of stones, fragments, or debris. These clearance rates appear high when compared with reports on monotherapy with ESWL or MTBE, suggesting a positive effect of a combined approach in selected patients. Two patients exhibited recurrent stones after six and seven months, respectively. PMID- 1864204 TI - Successful shock-wave lithotripsy of bile duct stones using ultrasound guidance. AB - Eighteen patients with 41 gallstones in the common bile duct, common hepatic, cystic, and intrahepatic ducts underwent shock-wave lithotripsy using the electrohydraulic Sonolith 3000 lithotripter. Lithotripsy was performed using ultrasound guidance alone under intravenous analgesia/sedation. All patients previously had failed stone extraction via retrograde endoscopy, T-tube, or cholecystostomy. Lithotripsy was performed according to an FDA-approved protocol allowing a maximum of two 2500 shock-wave treatments at a 48 hr interval. Following the final lithotripsy or cholangiographic evidence of stone fragmentation, residual fragments were removed via endoscopic or percutaneous route within 24-72 hr. Ultrasound localization of gallstones was aided by continuous infusion of the common bile duct with saline solution. In 15 of the 18 patients, complete fragmentation of the stones was accomplished, two had minimal fragmentation, and one with an encysted stone had no fracturing. No serious complications were encountered. Overall nonsurgical stone-free success rate was 17 of 18 patients, indicating biliary duct stones can be successfully treated using an ultrasound-guided lithotripter and intravenous sedation alone. PMID- 1864205 TI - One gram of aspirin per day does not reduce risk of hospitalization for gallstone disease. AB - Data from 4524 patients in a randomized, controlled trial of aspirin were analyzed to determine if aspirin reduced the risk for hospitalization for gallstone disease. Aspirin at a dose of 1000 mg/day did not reduce the risk of hospitalization for gallstones. Hospitalization rates for gallstone disease were consistent with national rates, and the data confirmed previous associations of gallstone disease with age, elevated serum triglycerides, obesity, and female gender. PMID- 1864206 TI - Gallbladder function and gastric liquid emptying in achalasia. AB - Because of evidence that the abnormalities in achalasia are not restricted to the distal esophagus, we investigated gallbladder function by cholescintigraphy in the steady state and in response to CCK and the scintigraphic gastric emptying of a liquid caloric meal in 10 individuals with achalasia and 10 normal controls. No abnormalities were found during the filling phase of the gallbladder but seven of the 10 patients showed a 50% reduction in the ejection fraction (39.4% +/- 30.4 vs 80.3 +/- 8.3 of controls, mean +/- SD, P = 0.007) and a slower than normal ejection phase (9.1%/min +/- 6.6 vs 18.1 +/- 4.5, P = 0.02. In eight of the 10 patients, gastric liquid emptying was accelerated with a T1/2 of 41.5 min +/- 15.4 vs 74.7 min +/- 11.5 in the controls (P = 0.007). It is concluded that in some achalasia patients extraesophageal functional abnormalities of the gastrointestinal tract may be found. Whether these findings are promoted by degenerative charges of extraesophageal nerve fibers as well as their clinical significance require further investigations. PMID- 1864208 TI - Secretory diarrhea following a dog bite. AB - Overwhelming sepsis is rarely complicated by secretory diarrhea. We present a case of fulminant sepsis associated with dermatologic manifestations, disseminated intravascular coagulation (DIC), and a severe secretory diarrhea that has not previously been described. This followed a dog bite, and the patient was otherwise healthy. The combination of septic shock, skin lesions, and DIC occurring after a dog bite has been attributed to dysgonic fermentor 2 organisms, now called Capnocytophaga canimorsus, but none were cultured in this case (7). Dysgonic fermentor-2 may be a new cause of secretory diarrhea and should be considered in the differential diagnosis of overwhelming sepsis associated with diarrhea. PMID- 1864207 TI - Smoking, the oral contraceptive pill, and Crohn's disease. AB - Both cigarette smoking and the oral contraceptive pill have been implicated as aggravating factors in Crohn's disease. Based upon the recent demonstration of multifocal gastrointestinal infarction in Crohn's disease, a possible pathogenic mechanism for this condition, we propose how smoking and the oral contraceptive pill may potentiate a tendency for focal thrombosis and hence exacerbate the activity of Crohn's disease. PMID- 1864209 TI - Yersinia enterocolitica infection with ileal perforation associated with iron overload and deferoxamine therapy. AB - Despite the frequency of gastrointestinal disease caused by Yersinia enterocolitica, intestinal perforation is a rare complication of this infection and to date only eight cases have been reported in the English literature. We describe a case of this unusual condition in a 17-year-old male patient with thalassemia intermedia requiring transfusion, who was also taking deferoxamine. The severity of the clinical picture is probably due to the increased virulence of Yersinia enterocolitica in the presence of deferoxamine and iron. PMID- 1864210 TI - Collagenous colitis with involvement of terminal ileum. AB - We present a case of collagenous colitis with evidence of terminal ileal involvement. The patient suffered from chronic watery diarrhea of three months' duration, and colonoscopy revealed a normal endoscopic appearance. Histologic examination of biopsies revealed a broad subepithelial band of collagen, with similar histologic findings in the terminal ileum. Additionally, the patient exhibited abnormalities of d-xylose and vitamin B12 absorption, although there were no clinical signs of malabsorption. Biopsy of the proximal small intestine was normal. The significance of these findings for the definition of the clinicopathologic entity of collagenous colitis and its pathogenesis are discussed. PMID- 1864211 TI - Portal vein thrombosis complicating endoscopic variceal sclerotherapy. Convincing further evidence. AB - Portal vein thrombosis occurred in a patient who bled from gastric varices that developed after obliteration of esophageal varices by endoscopic sclerotherapy. This complication was recognized only at surgery when thrombectomy and endovenectomy preceded the successful placement of an end-to-side portocaval shunt. At histopathology, the presence of an amorphous, eosinophilic material staining negatively for fibrin and similar to sclerosant injected at sclerotherapy was observed within the clot. This latter finding, previously unreported, provides convincing evidence for the causal relationship of portal vein thrombosis to endoscopic sclerotherapy. PMID- 1864212 TI - Familial enteric neuropathy with pseudoobstruction. AB - We report a case of autosomal dominant chronic intestinal pseudoobstruction secondary to a familial enteric neuropathy. Esophagogastrointestinal manometry studies in the index case showed decreased postprandial contractile frequency with normal amplitude of pressure activity in the stomach and small bowel. Pupillary function and autonomic reflexes were all normal, excluding an extrinsic autonomic neuropathy of the viscera. Histologic examination of the small intestine by hematoxylin and eosin stains revealed normal smooth muscles but a reduced number of neurons in the myenteric plexus without inflammatory cells or neuroNal intranuclear inclusions. Histologic examination of the myenteric plexus using the sections taken along the longitudinal axis of the intestine, stained with silver by the Smith technique, disclosed decreased numbers of argyrophilic neurons and degeneration of neurons and axons; however, there was no reactive increase in the number of glial cell nuclei. The patient's mother had suffered from chronic intestinal pseudoobstruction, which did not abate following extensive small bowel resection. This is the third family reported with an autosomal dominant enteric neuropathy unassociated with evidence of extrinsic autonomic or peripheral neuropathy. Subtotal resection of the small bowel was followed by recurrence of the pseudoobstruction syndrome in both affected members of the family. PMID- 1864213 TI - Omeprazole: gastrin and gastric data. PMID- 1864214 TI - Resection of intestinal bypass blind loop. PMID- 1864215 TI - Pancreatic duct changes. PMID- 1864216 TI - Antimony electrodes for in vivo pH monitoring. PMID- 1864217 TI - Antimony electrodes. PMID- 1864218 TI - Nonpharmacological treatment of hypertension in diabetes mellitus. AB - Hypertension may be partially or completely controlled by appropriate use of nondrug therapies. Because diabetic patients are so often hypertensive and because the same nondrug therapies effective for treatment of hypertension may also benefit the diabetes, the use of nondrug therapies is particularly important in these patients. Evidence about the effectiveness of various nondrug therapies is provided along with practical suggestions to improve patient adherence to them. PMID- 1864219 TI - Insulin and cardiovascular disease. Paris Prospective Study. AB - The Paris Prospective Study is a long-term investigation of coronary heart disease (CHD) risk factors in a large population of working men. The baseline cohort included 7028 men, 6093 who had a 75-g oral glucose tolerance test with measurement of plasma insulin and glucose levels (0 and 2 h) and 125 who were known non-insulin-treated diabetic patients. After a mean follow-up of 11 yr, 126 deaths ascribed to CHD were reported. Major independent predictors of CHD death were blood pressure, smoking, plasma cholesterol level, and fasting and 2-h postload plasma insulin level. Impairment of glucose tolerance, including overt diabetes, did not rank as an independent predictor when other baseline variables were accounted for. In the subset of the baseline cohort who presented with impaired glucose tolerance or diabetes (n = 943), 26 died from CHD during the follow-up. The strongest independent predictor of subsequent CHD death in this subsample with abnormal glucose tolerance was plasma triglyceride level. In view of the accumulating evidence that hyperinsulinemia and hypertriglyceridemia generally occur in the same type of subjects, in relation to insulin resistance and central obesity, the epidemiological findings of the Paris Prospective Study and of other investigations support the hypothesis that a constellation of mild metabolic abnormalities may play a deleterious role with regard to cardiovascular disease risk. PMID- 1864220 TI - Hyperinsulinemia or increased sympathetic drive as links for obesity and hypertension. AB - The association of obesity with hypertension has been amply demonstrated in cross sectional, longitudinal, and dietary-intervention studies, but the mechanisms remain enigmatic. Both conditions are independently characterized by similar metabolic alterations, i.e., glucose intolerance, dyslipoproteinemia, elevated serum uric acid, and inadequate Na+ transport. Obesity, hypertension, and these metabolic alterations are associated with hyperinsulinemia/insulin resistance. The degree of these alterations is lowest in lean hypertensives, intermediate in obese normotensives, and greatest in obese hypertensives, but mortality risk is highest in lean hypertensives. This apparent discrepancy may be related to the divergent hemodynamic characteristics, possibly indicating different etiology, of lean and obese hypertensives, i.e., contracted blood volume, increased total vascular peripheral resistance, and normal sympathetic drive in the former, expanded blood volume, normal peripheral resistance, and increased sympathetic drive in the latter. Current knowledge suggests that the interrelationships of obesity and hypertension with the metabolic alterations could be mediated by high carbohydrate and fat consumption and low physical activity, resulting in obesity and separate pathways in hyperinsulinemia and increased sympathetic drive, leading to a double vicious cycle. In one, hyperinsulinemia and the consequent insulin resistance would compound one another. In the second, the increasing hyperinsulinemia would increasingly stimulate the sympathetic nervous system. This double vicious cycle could result in increasing hemodynamic and metabolic derangements causing hypertension, diabetes, and atherosclerotic cardiovascular disease (ASCVD). The association of lean hypertension with ASCVD may be through other mechanisms, e.g., hemodynamic forces on the vascular endothelium. PMID- 1864221 TI - Obesity and hypertension. AB - There is a close association of obesity with hypertension through mechanisms not now understood. Hypertension occurs frequently in industrialized societies where weight gain with advancing years is a common feature and is rare in primitive societies where weight and age are negatively correlated. Hemodynamically, obesity is characterized by an expanded blood volume and increased cardiac output. Hypertension results if/when systemic vascular resistance fails to decrease as cardiac output increases. When calorie restriction leads to weight loss, both blood volume and cardiac output decrease; when the blood pressure falls, this is because peripheral resistance is unchanged. Weight-loss programs are helpful for the obese hypertensive because when hypertension is mild, blood pressure often (but not always) normalizes. Also, weight loss has been shown to decrease antihypertensive drug requirements. Interest in obesity-associated hypertension focuses on hyperinsulinemia/insulin resistance as causative factors. Although the evidence is tempting, it is far from conclusive and it seems likely that the mechanism of this type of hypertension is as multifactorial as those of other types. PMID- 1864222 TI - Calcium metabolism in hypertension and allied metabolic disorders. AB - Data suggest a critical role for Ca metabolism in the pathophysiology of hypertensive disease. Intracellularly, all hypertension displays elevated cytosolic free-Ca2+ and suppressed free-Mg2+ levels. Extracellularly, however, heterogeneous defects in Ca and Mg metabolism are observed. This apparent divergence may be explained by considering all hypertension as the expression, in varying degrees, of two underlying Ca-related mechanisms: one (salt sensitive, low renin, Ca(2+)-antagonist sensitive) dependent on inappropriate cellular Ca2+ uptake from the extracellular space and the other (salt insensitive, renin dependent, Ca(2+)-antagonist insensitive) dependent on increased cellular Ca2+ release from intracellular sites. Recent work highlights the role of 1,25 dihydroxyvitamin D3 and the newly described parathyroid hypertensive factor in volume-dependent low-renin forms of hypertension. Altered cellular ion handling may also explain metabolic and clinical correlates of hypertension, e.g., peripheral insulin resistance, hyperinsulinemia, obesity, and non-insulin dependent diabetes mellitus (NIDDM). Thus, all subjects with NIDDM, whether hypertensive or not, display the same elevated cytosolic free-Ca2+ and suppressed free-Mg2+ levels observed in hypertension. Furthermore, adiposity, the level of blood pressure, and fasting and postglucose hyperinsulinemia are all closely and quantitatively related to intracellular free-Ca2+, free-Mg2+, and pH levels. This suggests a broader hypothesis, in which hypertension, obesity, insulin resistance, and NIDDM, each usually considered a distinct clinical entity, represent different clinical expressions of a common defect in cellular ion handling, hence explaining their frequent clinical coexistence in the general population. PMID- 1864223 TI - Effects of cefonicid on platelet aggregation. AB - Beta-lactam antibiotics may interfere with platelet aggregation by inhibiting the binding of agonists of platelet aggregation, such as ADP and collagen, to specific receptor sites. The aim of this study was to evaluate in vitro the effects of cefonicid, a semi-synthetic cephalosporin, on platelet aggregation. Spontaneous platelet aggregation and platelet aggregation induced by ADP and collagen were assessed. Platelets from healthy subjects were incubated with cefonicid at final concentrations of 0.1 mg/ml, 1 mg/ml and 10 mg/ml (0.1 mg/ml is the concentration of cefonicid achieved in humans at therapeutic doses). When compared with saline, cefonicid at a concentration of 0.1 mg/ml had no effect on platelet aggregation, but at 1 mg/ml it inhibited ADP-induced aggregation and at 10 mg/ml it also inhibited aggregation induced by collagen. These findings suggest that therapeutic doses of cefonicid do not affect platelet aggregation. PMID- 1864224 TI - The cellular mechanism of action of bisphosphonates. AB - Present understanding of the cellular mechanism of action of bisphosphonates as in vitro and in vivo inhibitors of bone resorption is reviewed. This mechanism appears to involve the osteoclast at more than one stage of its maturation process, and way well be receptor-mediated, although the molecular mechanism itself is thus far unknown. PMID- 1864225 TI - Effect of propionyl carnitine on cardiac energy metabolism evaluated by the release of purine catabolites. AB - The assessment of purine release in perfusion fluid is a new method (Zucchi et al.) which allows a continuous evaluation of energy metabolism in isolated perfused rat heart. Purine release in fact is related to the imbalance between ATP formed and utilized in myocytes. With this method we have investigated the effect of propionyl carnitine, carnitine and propionate on the working heart. The presence of millimolar concentrations of propionyl carnitine decreases purine release and improves cardiac performance as measured by cardiac output and double product (product of heart rate and aortic systolic pressure). Propionate has no effect, while carnitine slightly decreases purine release. The property shown by propionyl carnitine in decreasing the imbalance between ATP production and utilization and in improving cardiac performance is due to its ability to improve the energy metabolism of cardiomyocytes. This compound supplies oxidizable substrates and intermediates to the tricarboxylic acid cycle. In the presence of propionyl carnitine the myocardium therefore responds better to the sudden requirements of overwork and shows better functional efficiency for longer periods. PMID- 1864226 TI - L-acetylcarnitine enhances functional muscle re-innervation. AB - The efficacy of L-acetylcarnitine and L-carnitine treatment on motor re innervation was analyzed by evaluating different muscular parameters describing functional muscle recovery after denervation and re-innervation. The results show that L-acetylcarnitine markedly enhances functional muscle re-innervation, which on the contrary is unaffected by L-carnitine. The medial gastrocnemius muscle was denervated by cutting the nerve at the muscle entry point. After 20 days the sectioned nerve was resutured into the medial gastrocnemius muscle, and the extent of re-innervation was monitored 45 days later. L-acetylcarnitine-treated animals show significantly higher twitch and tetanic tensions of re-innervated muscle. Furthermore the results, obtained by analysing the twitch time to peak and tetanic contraction-relaxation times, suggest that L-acetylcarnitine mostly affects the functional re-innervation of slow motor units. The possible mechanisms by which L-acetylcarnitine facilitates such motor and nerve recovery are discussed. PMID- 1864227 TI - Topical application of superoxide dismutase cream. AB - A superoxide dismutase (SOD) cream containing 0.6 mg/ml of bovine SOD was prepared. It was applied locally onto the skin and mucosal lesions caused by progressive systemic sclerosis (PSS), systemic lupus erythematosus (SLE), Behcet's disease, herpes simplex and burns. The lesions and symptoms were rapidly improved in many cases after its administration, even when the symptoms were stabilized for several weeks before the treatment. Although the trial was open labelled, the topical application of SOD was concluded to be effective for these conditions. PMID- 1864229 TI - [Possibility of integration of the hospice idea into the hospital structure]. PMID- 1864228 TI - Effect of solcoseryl on antitumour action and acute toxicity of some antineoplastic drugs. AB - The in vivo effect of Solcoseryl on the antitumour activity and acute toxicity of some antineoplastic drugs was examined. It was found that Solcoseryl does not inhibit the antineoplastic effectiveness of the drugs against transplantable P 388 leukaemia in mice. Studies of the effect of Solcoseryl on acute toxicity of selected antineoplastic drugs in mice revealed that the biostimulator could exert a modifying influence. The prior administration of Solcoseryl significantly decreases the acute toxicity of methotrexate but has no effect on acute toxicity of 5-fluorouracil, increases the acute toxicity of bleomycin and vinblastine and has no effect on acute toxicity of methotrexate and mitoxantron. On the other hand, Solcoseryl administered simultaneously with the antineoplastic drugs increases acute toxicity of 5-fluorouracil, bleomycin and mitoxantron. The protective effect of the biostimulator noted exclusively against acute toxicity of 5-fluorouracil was also observed after multiple administration of this anticancer drug. PMID- 1864230 TI - [Perinatal medicine--interdisciplinary cooperation between obstetrics and neonatology. Introduction into the main topic]. PMID- 1864231 TI - [Experiences of a pediatric nurse in an intensive care unit for premature infants]. PMID- 1864232 TI - [Neonatal intensive care units in obstetrics departments]. PMID- 1864233 TI - [Emphasis in the nursing of premature infants with respiratory distress syndrome]. PMID- 1864234 TI - [Psycho-biological aspects in the nursing of premature infants]. PMID- 1864235 TI - [Continuing nursing education "Pediatric Intensive Care"]. PMID- 1864236 TI - [Only together can we succeed. Society for aid to premature infants and infants at risk "Das Fruhchen"--cooperation between professional personnel and affected parents]. PMID- 1864237 TI - [Ethics in neonatology. Care of the premature--an ethical challenge for the neonatologist]. PMID- 1864238 TI - [Ethics commissions in neonatology]. PMID- 1864239 TI - [Limits to the obligation of medical treatment in the most severely disabled newborn infants]. PMID- 1864240 TI - [Regulation of working time]. PMID- 1864241 TI - ["Totally normal". Report of experiences from the Bremen-Ost Central Hospital with the Bremen Model for the normalization of the working time in nursing]. PMID- 1864242 TI - ["Service plan" and "personnel pool". Possibilities for the nursing administration to direct the distribution of personnel to avoid over- or under coverage]. PMID- 1864243 TI - [The prognostic value of evoked potentials in early neurologic rehabilitation of patients with the apallic syndrome]. AB - In 22 patients with apallic syndrome brainstem auditory and somatosensory evoked potentials were recorded, in 8 patients the course during rehabilitation was observed. Clinically the patients were scored with Glasgow-coma scale, Karnofsky index and Goldenberg-scale. The outcome of rehabilitation was estimated by the "Glasgow-outcome scale". No correlation was found between results of evoked potentials and clinical state. First evoked potentials measurements of apallic patients allowed no prognosis. Evoked potentials are an important prognostic factor after severe head trauma, but have no value for the prognosis of apallic patients. PMID- 1864244 TI - [Event-related potentials in schizophrenic patients in the acute phase and in remission]. AB - In 15 schizophrenic patients event-related potentials were recorded during an auditory two-tone-discrimination task in the acute phase and after remission. The control group consisted of ten healthy subjects of the same age. The schizophrenic patients showed reduced amplitudes of N1, P2 and P3 and prolonged latencies of N2 and P3 independent of neuroleptic medication and clinical state. We found no differences in the topographical distribution of P3 between schizophrenic patients and controls. The changes of the event-related potentials in the schizophrenic patients may be interpreted as electrophysiological correlates of basic disturbances in information processing in schizophrenia. PMID- 1864245 TI - [Magnetic stimulation using double coils--methodology and normal findings]. AB - Magnetic stimulation of the motor cortex and spinal nerve roots was investigated in a group of 45 normal subjects using double coils. Figure of eight coils allows for an isolated excitation of the motor cortex of one hemisphere which cannot be achieved with circular coils. To evoke compound responses in hand muscles the optimal position of the figure of eight coil is with its centre about 5 cm lateral of the vertex and contralateral to the target muscle. The coil handle is in frontal position (occipito-frontal direction of the stimulation current in the coil; physical current definition is used resembling the electron flow from - to +). For the excitation to leg muscles the double coil centre is over the vertex with the handle contralateral to the target muscle (frontal current direction). Cervical roots can easily be stimulated using figure of eight coils with the handle contralateral to the target muscle and the coil centre over the root segment. PMID- 1864246 TI - [Changes in the responses of motor units to transcranial magnetic stimulation in patients with multiple sclerosis and stroke]. AB - In multiple sclerosis and stroke the muscle responses to transcranial magnetic stimulation are frequently delayed, reduced in amplitude or absent. To investigate the underlying pathophysiological mechanisms, responses of single motor units to transcranial magnetic stimulation were analysed using peri stimulus time histograms. The following response patterns were detected: 1. prolongation of latency and duration of the primary peak which occurs in healthy controls 17 to 30 ms after the stimulus and has a duration of 2 to 8 ms, 2. lack of an excitatory response, 3. prolongation of the interval between sub-peaks within the primary peak and 4. multimodal responses. Possible mechanisms for these changes are: reduction and dispersion of conduction velocities in corticospinal axons associated with impaired summation of excitatory post synaptic potentials at the spinal motoneurone, frequency-dependent or complete conduction block in corticospinal neurones and compensatory activation of other descending motor pathways. PMID- 1864247 TI - [Activation of the semantic memory by subliminal word stimuli? An analysis using event-related potentials]. AB - There is a hotly debated question as to whether the meaning of a word can be assessed in the lexicon before conscious identification of this word is possible. Some authors have reported shorter lexical decision times for words, which had been preceded by primes, that had been masked below threshold. This effect was taken as evidence for an automatic activation of the lexicon by the unidentified prime. We report an ERP study using the N400 potential and lexical decision time as an index for associative activation of the lexicon. In a condition with supra threshold primes the typical acceleration of lexical decision time and reduction of N400 amplitude was found for semantically related target words. In the sub threshold condition, however, no evidence was found for priming in RT and ERP data. This pilot data, as well as previous RT studies, question the findings gathered on sub-threshold priming. No dissociation between RT and ERP parameters was found in the present study. PMID- 1864248 TI - [Quantification of artefacts in surface EMG by validating the lower frequency limit in clinico-physiologic studies]. AB - The surface-EMG becomes more and more important because computer assisted analysing systems can be applied. The occurrence of artefacts makes it very difficult to compare several recorded EMG channels with each other. In this study a frequency related quantification of movement artefacts and ECG-related influences on the EMG is carried out to select a suitable lower cut-off frequency for surface-EMG investigations. In 764 monopolar surface-EMG-recordings of the neck and back muscles the solely artefact-caused part of EMG-segments was analysed and quantified by means of modelling methods. PMID- 1864249 TI - [Techniques of determining saccadic parameters]. AB - For the analysis of saccadic eye movements two values were to be computed: the latency of the reaction and the maximum velocity reached by the eye finding the new visual point. The waveform is disturbed especially by noise. With this method, the impurity level can be reduced nearly completely without destroying the curve shape of the saccade. PMID- 1864250 TI - [Attention deficits and schizophrenia. Multidisciplinary approaches and the Stroop's test]. AB - Since McGhie & Chapman's (1961) pioneering work, there have been continual attempts to clarify the link between attentional disturbances observable in schizophrenics and their schizophrenic symptoms. Venables (1964, 1977) claims that this diminution is a consequence of a badly controlled arousal, resulting in an inadequate filtering at the level of sensory input. Although the notion of a faulty sensory filter is simple and intellectually satisfying, this idea rapidly met with articulate opposition. Broadbent himself, in 1971, revised his model to take into account the way in which semantic aspects influence selective attention, and proposed the existence of a second stage of information processing, coming after the sensory filter. It became increasingly clear that progress in understanding selective attention would depend upon more centrally directed approaches. In 1935, Stroop developed an ingenious way of studying selective attention. In his task, an "automatic", overlearned task (reading short words aloud) is put into conflict with a slightly more difficult task (colour naming): the subject has to name the colour of the ink in which a word is printed, but the word itself is the name of a different colour. For instance, when the word "blue" is written in red ink, the correct response is "red". Typically, subjects find it difficult to inhibit the reading response, and take significantly more time to name a colour that forms an incompatible word than take to name the colour of a row of letters "x". This increased reaction time for the incompatible condition is attributed to an "interference" caused by the verbal information contained in the double stimulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864251 TI - [Biological psychiatry and current classifications of depressive disorders]. AB - By means of a review of genetic, biological and neurophysiological studies, we attempted to validate the DSM III-R depressive disorder categories. Genetic studies support the distinction between bipolar and recurrent major (unipolar) depression although genetic heterogeneity and variable phenotypic expressivity have been suggested in bipolar depression. Biological and neuroendocrine abnormalities in depression seem to relate more to a particular symptomatological profile than to a specific depressive subtype including the bipolar-unipolar dichotomy. For example, catecholamines and serotonin metabolism seem to reflect respectively psychomotor status and aggressiveness in depression. Using genetic and biological criteria, major depression with psychotic features is the best validated category of the four main DSM-R major depressive subclasses or specifications (psychotic, chronic, melancholic, seasonal). Psychotic depression seems to constitute the most coherent subgroup and biological abnormalities such as dexamethasone non suppression and shortened REM latency are very often observed. An important confounding variable in these biological validation studies is the severity of the depressive state. Psychotic depression is considered to be a more severe depressive subtype and also shows marked biological disturbances. Conversely, in seasonal depression, a less severe depressive subtype, CSF monoamine metabolism abnormalities, dexamethasone non suppression and shortened REM latency could not clearly be demonstrated. Genetic studies show that early onset dysthymia and cyclothymia could be part of the affective spectrum and some maintain that these two clinical entities are attenued forms of bipolar or recurrent major depression. PMID- 1864252 TI - [Noradrenaline and cerebral aging]. AB - The central functions of norepinephrine (NE) are a recent discovery: regulation of alertness and of the wakefulness-sleep cycle, maintenance of attention, memory and learning, cerebral plasticity and neuro-protection. The anatomical, histological, biochemical and physiological properties of the central noradrenergic system: extreme capacity for ramification and arborization; slow conduction, non-myelinized axons with extrasynaptic varicosities producing and releasing NE; frequency of co-transmission phenomena, and; neuromodulation with fiber effect responsible for improvement in the signal over background noise ratio and selection of significant stimuli form a true interface between the outside world and the central nervous system, notably for the neocortex in the context of the cognitive treatment of information. This central noradrenergic system is involved in the neurophysiology and the clinical features of cerebral aging (ideation-motor and cognitive function slowing down, loss of behavioral adjustment), neuro-degenerative disorders (SDAT, Parkinson's disease), certain aspects of depression and less obvious conditions (head injuries, sequelae of cerebrovascular accidents, sub-cortical dementia). The recent development of medications improving alertness (adrafinil, modafinil) with a pure central action and specifically noradrenergic, may contribute to an improvement in these multifactorial disorders. PMID- 1864253 TI - [Plasma levels and membrane transports in red blood cell of tyrosine and tryptophane in depression. Evaluation at baseline and recovery]. AB - The erythrocyte membrane transports (MT) of L-tyrosine and L-tryptophan, as well as their plasma levels, were measured in 143 depressed patients after a wash-out period of one week and before any antidepressant treatment, and then at regular intervals until they recovered. 49 normal subjects served as a control group. The perturbations of these biologic variables at baseline were different according to diagnostic groups (DSM III), compared to controls: significant decrease of the two MT in depressed bipolar disorders; significant decrease of MT in depressed bipolar disorders; significant decrease of MT tyrosine and significant increase of MT tryptophan in recurrent major depressions; no significant changes of MT in dysthymic disorders. The plasma levels of tyrosine and total tryptophan show a significant diminution in the 3 groups. The study of the evolution of these same variables after antidepressant treatment show a return to normal of the MT at recovery, as well as the plasma levels of tyrosine. The plasma levels of tryptophan stay low in depressed bipolar disorders and recurrent major depressions. PMID- 1864254 TI - [Plasma MHPG, peripheral noradrenergic marker and hormonal plasma levels of cortisol-T3-T4-TSH in depressive syndromes]. AB - Based on the hypocatecholaminergic hypothesis in the depressive syndromes, this survey on 30 depressed patients compared to 21 control patients, attempts to state exactly the potential interactions between the noradrenergic system and the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid neuroendocrine axis. The biological indices used during this survey are: total plasmatic MHPG, the basic plasmatic cortisol, the thyroid hormones T3, T4, free T4, and the TSH. The results of this survey reveal a significative increase of the basic plasmatic cortisol among the depressed patients, including dysthymics, a decrease of the plasmatic MHPG during major depressions, and a significant fall of the total T3 among depressed men, as well as some correlations between the different axes, the interpretation of which remains "ticklish". PMID- 1864255 TI - [Treatment of resistant depression with the citalopram-lithium combination. Methodology of a double-blind multicenter study and preliminary results]. AB - Citalopram, a new bicyclic antidepressant, is the most selective serotonin reuptake inhibitor. In a number of double-blind controlled studies, citalopram was compared to placebo and to known tricyclic antidepressants. These studies have shown their efficacy and good safety. The inefficacy of a psychotropic treatment in at least 20% of depressives has led a number of authors to propose original drug combinations and associations, like antidepressant/lithium (Li), antidepressant/sleep deprivation (agrypnia), antidepressant/ECT, or antidepressant/LT3. The aim of this investigation is to evaluate the clinical effectiveness and safety of a combined citalopram/lithium treatment in therapy resistant patients, taking account of serotonergic functions, as tested by the fenfluramine/prolactin test, and of drug pharmacokinetics and pharmacogenetics of metabolism. DESIGN OF THE STUDY: A washout period of 3 days before initiating the treatment is included. After an open treatment phase of 28 days (D) with citalopram (20 mg D1-D3; 40 mg D4-D14; 40 or 60 mg D15-D28; concomitant medication allowed: chloral, chlorazepate), the nonresponding patients [less than 50% improvement in the total score on the 21 item-Hamilton Depression Rating Scale (HDRS)] are selected and treated with or without Li (randomized in double blind conditions: citalopram/Li or citalopram/placebo) during the treatment (D29 D35). Thereafter, all patients included in the double-blind phase subsequently receive an open treatment with citalopram/Li for 7 days (D36-D42). The hypothesis of a relationship between serotoninergic functions in patients using the fenfluramine/prolactin test (D1) and the clinical response to citalopram (and Li) is assessed. Moreover, it is evaluated whether the pharmacogenetic status of the patients, as determined by the mephenytoin/dextromethorphan test (D0-D28), is related to the metabolism of fenfluramine and citalopram, and also to the clinical response. CLINICAL ASSESSMENT: Patients with a diagnosis of major depressive disorders according to DSM III are submitted to a clinical assessment of D1, D7, D14, D28, D35, D42: HDRS, CGI (clinical global impression), VAS (visual analog scales for self-rating of depression), HDRS (Hamilton depression rating scale, 21 items), UKU (side effects scale), and to clinical laboratory examens, as well as ECG, control of weight, pulse, blood pressure at D1, D28, D35. Fenfluramine/prolactin test: A butterfly needle is inserted in a forearm vein at 7 h 45 and is kept patent with liquemine. Samples for plasma prolactin, and d- and l-fenfluramine determinations are drawn at 8 h 15 (base line). Patients are given 60 mg fenfluramine (as a racemate) at 8 h 30. Kinetic points are determined at 9 h 30, 10 h 30, 11 h 30, 12 h 30, 13 h 30. Plasma levels of d- and l-fenfluramine are determined by gas chromatography and prolactin by IRNA. Mephenytoin/dextromethorphan test: Patients empty their bladders before the test; they are then given 25 mg dextropethorphan and 100 mg mephenytoin (as a racemate) at 8 h 00. They collect all urines during the following 8 hours. The metabolic ratio is determined by gas chromatography (metabolic ratio dextromethorphan/dextrorphan greater than 0.3 = PM (poor metabolizer); mephenytoin/4-OH-mephenytoin greater than 5.6, or mephenytoin S/R greater than 0.8 = PM). Citalopram plasma levels: Plasma levels of citalopram, desmethylcitalopram and didesmethylcitalopram are determined by gas chromatography--mass spectrometry. RESULTS OF THE PILOT STUDY. The investigation has been preceded by a pilot study including 14 patients, using the abovementioned protocol, except that all nonresponders were medicated with citalopram/Li on D28 to D42. The mean total score (n = 14) on the 21 item Hamilton scale was significantly reduced after the treatment, ie from 26.93 +/- 5.80 on D1 to 8.57 +/- 6.90 on D35 (p less than 0.001). A similar patCitalopram, a new bicyclic antidepressant, is the most selective serotonin reu PMID- 1864256 TI - [Irreversible neurologic sequelae caused by lithium]. AB - Lithium therapy can induce acute toxic reactions especially during overdosage. Exceptionally, permanent neurologic sequelae persist after the acute toxic reaction. These sequelae are more often cerebellar symptoms. Dementia, parkinsonian syndromes, choreoathetosis, brain stem syndromes and peripheral neuropathies have also been described. They are defined as irreversible if they persist more than two months after the interruption of lithium treatment. These neurologic complications occur frequently after voluntary or accidental poisoning but they may be observed even if the serum lithium dosage is below toxic level. Risk factors other than overdose are not well identified. Neurologic lesions induced by lithium can occur in the first days of the treatment as well as after years of maintenance therapy. Age and psychiatric diagnosis do not seem to be correlated with an increased risk of lithium induced neurotoxicity. Sex may be a risk factor, because of an overrepresentation of women among the case reports. The lithium-neuroleptic combination is another possible (although controversial) risk factor precipitating the occurrence of irreversible neurologic sequelae. Haloperidol was first implicated, but it has been shown that others neuroleptics, in combination with lithium, can induce similar toxic reactions. Intercurrent somatic illness with pyrexia often precedes the acute toxic reaction, and special attention must be paid to patients treated by lithium when they become hyperthermic. Major surgery, concurrent treatment with diuretics, renal failure, low food intake or low-salt diet are more uncommon precipitating factors. Available pharmacological treatments have not yet proved to be helpful. Even when the lesions are irreversible, a functional improvement can be obtained by rehabilitation. Thirty one cases of irreversible neurologic sequelae are reviewed. PMID- 1864257 TI - [Concept of 2nd generation antidepressive agents]. AB - Since the discovery of imipramine and iproniazide, the tricyclic antidepressants (TCA) have maintained a significant role in the pharmacotherapy of depression, whereas the MAO-inhibitors play a minor role because of toxicity problems. However, even the tricyclics present problems and the research to obtain a new "second generation" of less toxic and more efficacious antidepressants have been fully justified. This research has been based on biological models of depression and/or the experimental effects of existing antidepressants. In spite of the considerable investments over 30 years, the validity of prevailing biological depression-models is uncertain. Among the experimental effects of existing antidepressants, their ability to inhibit the reuptake of noradrenaline and serotonin has attracted most attention, resulting in the development of very selective compounds. Likewise, new selective and in particular reversible MAO inhibitors have been developed. In light of the doubious validity of the experimental models, the clinical testing remains the crucial point. However, clinical trial methodology poses a number of problems, and there is much uncertainty concerning the efficacy of the heterogenous group of "second generation" antidepressants. Therefore, they are generally considered as antidepressants of second choice. PMID- 1864258 TI - Monoamine specificity of antidepressants and prediction of therapeutic response. AB - The increase of the availability of monoamines on synapses has been one of the proposed modes of action of antidepressants (AD), but few drugs are specific for one neurotransmitter system, there is a time lag of the onset of action and some substances increasing the availability of neurotransmitters do not improve mood. The monoamine hypotheses of AD mode of action seems too simplistic and hypotheses as the beta receptor down regulation theory or the restored efficient regulation of the dysregulated neurotransmitter system theory are more plausible. Prediction of AD treatment response is an important clinical issue due to the time lag of the onset of action. The dubious theory of monoaminergic specificity has been applied to the prediction of AD response. The pretreatment MHPG levels have been used for prediction of treatment response. Results are contradictory and inconclusive probably due to many methodological problems of this approach. Other monoamine pretreatment levels (5-HIAA, HVA) have also been used, again with inconclusive results. Other approaches based loosely on monoaminergic specificity of various AD such as platelet monoamine oxidase inhibition, platelet imipramine binding and monoamine precursors availability have been used without success. Thus the biological markers may not be useful for a successful prediction of the AD treatment outcome at present. PMID- 1864259 TI - [Role of pharmacogenetics in psychopharmacotherapy]. AB - Genetic polymorphism related to certain P450 isozymes, in particular the sparteine/debrisoquine oxygenase, is the dominant cause of interindividual variation in elimination of several drugs. If the pharmacokinetic variability is large, relative to the therapeutic index of the drug, the genetic polymorphism will be clinically important. If the dose cannot be adjusted on the basis of effect measurements, phenotyping may be a supplement or replacement for drug level monitoring which is otherwise relevant for such drugs. Several aspects as elucidated by the experience with the sparteine/debrisoquine oxidation polymorphism ought to be analysed: The role of active metabolites and their rate of formation and elimination, selective drug-drug interaction at the polymorphic isozyme or at alternative routes of elimination, the possible role of two or more polymorphic drug oxidation pathways, and the effect of saturable kinetics. The sparteine/debrisoquine oxidation polymorphism affects two major classes of drugs in psychopharmacology, the antidepressants and the neuroleptics, and this is the best example of clinical relevance of pharmacogenetic polymorphism. Routine use of phenotyping thus should be considered for psychiatry departments. PMID- 1864260 TI - [Clinical evaluation of new antidepressive agents]. AB - The second generation of antidepressants have been developed with the goal to reduce cardio-toxic effects and to further a more specific action on neurotransmitter systems. However some standardized actual parameters, clinical, biological and pharmacological may be accepted as reasonable elements in evaluating the therapeutic effects. Among them we will distinguish the diagnostic instruments which define categories of affective disorders; rating scales to assess gravity, the type of clinical test, duration of the test and finally those biological variables which should be an integral part of the evaluation of new antidepressants. PMID- 1864261 TI - [Pharmacovigilance and 2nd generation antidepressive agents]. AB - Genuine side effects of antidepressants are difficult to specify. Except for rare cases, imputability of a severe effect is questionable. However, several recent drug surveillance studies allow to better assess the tolerability of these compounds. The first is British: it compared the blood toxicity of mianserin and amitryptiline (Inman). The second (Henry) is based on the calculation of a lethal toxicity index (deaths per millions of prescriptions), varying with the different compounds. The third (Cooper) pools the data of all the comparative trials of fluoxetine as well as all the relevant effects noticed with this drug (more than 7,500 prescriptions in 1988). Antidepressants generally have to be used on a long term basis. The study of the safety of their long term use is absolutely necessary. PMID- 1864262 TI - [Clozapine in the treatment of schizophrenia]. PMID- 1864263 TI - [Clozapine. Management of hematologic risk]. PMID- 1864264 TI - Benzene-induced micronuclei formation in mouse fetal liver blood, peripheral blood, and maternal bone marrow cells. AB - The transplacental cytogenetic effects of benzene were studied by using the micronucleus test of polychromatic erythrocytes (PCE) found in both fetal liver and fetal peripheral blood, and were compared with PCE from maternal bone marrow. Timed-pregnant mice received single intraperitoneal doses of benzene (0, 109, 219, 437, or 874 mg/kg bw) on the 14th day of gestation and were sacrificed 21 hr after injection. Benzene elicited a significant increase (P less than 0.01) in the frequency of micronucleated polychromatic erythrocytes (MNPCE) in fetal liver blood cells (0.55 to 1.36%, control 0.18%) at doses of 219 to 874 mg/kg, and in fetal peripheral blood cells (0.49 to 0.58%, control 0.25%) and maternal bone marrow cells (0.53 to 0.70%, control 0.10%) at doses of 437 and 874 mg/kg. The data demonstrate that benzene is a moderate transplacental clastogenic agent, and that the mouse transplacental micronucleus test using fetal liver blood cells is a potentially more sensitive indicator of the genotoxicity of benzene than either fetal peripheral blood or maternal bone marrow cells. PMID- 1864265 TI - Characterization of a method for quantitating food consumption for mutation assays in Drosophila. AB - Quantitation of food consumption is necessary when determining mutation responses to multiple chemical exposures in the sex-linked recessive lethal assay in Drosophila. One method proposed for quantitating food consumption by Drosophila is to measure the incorporation of 14C-leucine into the flies during the feeding period (Thompson and Reeder: Environmental Mutagenesis 10:357-365, 1987). Three sources of variation in the technique of Thompson and Reeder have been identified and characterized. First, the amount of food consumed by individual flies differed by almost 30% in a 24 hr feeding period. Second, the variability from vial to vial (each containing multiple flies) was around 15%. Finally, the amount of food consumed in identical feeding experiments performed over the course of 1 year varied nearly 2-fold. The use of chemical consumption values in place of exposure levels provided a better means of expressing the combined mutagenic response. In addition, the kinetics of food consumption over a 3 day feeding period for exposures to cyclophosphamide which produce lethality were compared to non-lethal exposures. Extensive characterization of lethality induced by exposures to cyclophosphamide demonstrate that the lethality is most likely due to starvation, not chemical toxicity. PMID- 1864266 TI - Evaluation of the mutagenicity of beta-myrcene in mammalian cells in vitro. AB - The genotoxicity of the terpene beta-myrcene was evaluated in mammalian cells in vitro. Myrcene is the major constituent of oil of bay and hop which are used in the manufacture of alcoholic beverages. Myrcene is also present in lemon grass (Cymbopogon citratus), a plant widely used in Brazilian folk medicine. Recently, it was shown that myrcene is a very potent analgesic substance and might be an alternative to the already available analgesic drugs. Myrcene was tested up to 1,000 micrograms/ml (limit of solubility) in the presence and absence of S9-mix and did not induce chromosome aberrations and sister chromatid exchanges (SCEs) in human lymphocytes in vitro. Neither the mitotic index nor the proliferation index was influenced by the myrcene treatment. Myrcene did not cause increased mutation frequencies at the hprt-locus in V79-cells. Tests with and without S9 mix revealed negative results. There was no indication for induced cytotoxicity. However, myrcene reduced the SCE-inducing effect of cyclophosphamide in human lymphocytes in a dose dependent manner and also reduced the toxic and mutagenic effect of cyclophosphamide in V79-cells. Under the same test conditions, SCE induction by ethyl methanesulfonate (EMS) and benzo [a]pyrene (BP) was not significantly influenced by simultaneous myrcene treatment. The in vitro results show that myrcene is not mutagenic in mammalian cells, but has antimutagenic properties. The possibility that myrcene exerts its antimutagenic activity by inhibiting certain forms of the cytochrome P-450 isoenzymes required for activation of premutagens and precarcinogenes is discussed. PMID- 1864267 TI - Inhibitory effect of lichen constituents on mutagenicity induced by heterocyclic amines. AB - Physodic acid, one of the main constituents of Hypogymnia enteromorpha, inhibited the mutagenicity of indirect mutagens, including benzo[a]pyrene and heterocyclic amines in Salmonella typhimurium TA 98. In contrast, it was not effective against direct mutagens such as 6-nitropiperonal and adriamycin. Its antimutagenicity was not associated with free-radical scavenging or antioxidative activities. Physodic acid seemed to inhibit the formation of reactive metabolites, such as N-hydroxy Trp-P-2, by blocking the hepatic microsomal oxidation systems. Another component of H. enteromorpha, physodalic acid, also inhibited mutagenicity of a heterocyclic amine, Trp-P-2, in S. typhimurium TA 98, even though it was reportedly mutagenic in S. typhimurium TA 100. PMID- 1864268 TI - Genotoxicity of nitrated polycyclic aromatic hydrocarbons and related structures on Escherichia coli PQ37 (SOS chromotest). AB - To determine the genotoxicity of nitrated polycyclic aromatic hydrocarbons and related molecules (nPAH) we examined 24 compounds representative of nitroanthracenes, nitrofluorenes, nitronaphthalenes, nitropyrenes, and nitroquinolines for genotoxicity in Escherichia coli PQ37 (SOS-chromotest). To enhance the sensitivity of the tester strain and optimize metabolic activation we used a modified test protocol and S9-mix composition. All chemicals with the exception of 9-nitroanthracene, 1- and 2-nitronaphthalene, 2-methyl-1 nitronaphthalene, and 5-, 6-, and 8-nitroquinoline induced the SOS system of E. coli PQ37. As expected from previously referred mutagenicity studies, the highest SOS inducing potencies (SOSIP) were exhibited by the dinitropyrenes (SOSIP = 151 416), 4-nitroquinoline-N-oxide (SOSIP = 62), and 3-nitrofluoranthese (SOSIP = 16). Except for some nitronaphthalenes, the nPAHs showed their highest genotoxicity in the absence of an exogeneous metabolic activation system. The results were compared to those reported for the bacterial mutagenicity of these substances in Salmonella typhimurium TA98. PMID- 1864269 TI - Chemical mutagenesis at the thymidine kinase locus in L5178Y mouse lymphoma cells: results for 31 coded compounds in the National Toxicology Program. AB - Experimental data from the testing of 31 chemicals for mutagenicity at the TK locus in L5178Y mouse lymphoma cells are presented and evaluated. If mutagenic activity was not obtained for the chemical added to suspension cultures for 4 hr, then the testing was repeated in the presence of hepatic S9 mix prepared from Aroclor 1254-induced male Fischer 344 rats. Multiple trials were performed for each chemical, and mutagenic treatments were analyzed for the induction of small and large mutant colony populations. Twelve chemicals were not detected as mutagenic, one (ascorbic acid) was questionable, and 18 were evaluated as mutagenic. These results were used in the evaluations presented by Tennant et al. [Science 236:933-941, 1987] in a critical comparison of four in vitro genotoxicity assays with rodent carcinogenicity results. The mouse lymphoma assay results were in general agreement with the carcinogenicity studies. Discordant evaluations with respect to carcinogenicity (four false negatives and six false positives) were discussed from the standpoint of how the predictive performance of the in vitro mutation assay might be improved. PMID- 1864270 TI - Genotoxicity of the fungicide dichlofluanid in seven assays. PMID- 1864271 TI - Intracellular distribution and activity of antibiotics. AB - Intracellular penetration, accumulation and disposition are important parameters governing the activity of antibiotics against intracellular bacteria. Beta lactams diffuse into but do not accumulate in phagocytes, probably because of their acidic character. Aminoglycosides are too polar to pass across membranes and are therefore only taken up slowly by endocytosis, which results in an exclusively lysosomal localization. Lincosaminides, macrolides and fluoroquinolones all accumulate in phagocytes, the two former classes of drugs showing both a cytosolic and a lysosomal localization. Fluoroquinolones appear to be entirely soluble in cells. Analysis of their activity in a model of Staphylococcus aureus-infected J774 macrophages has revealed low activity of clindamycin, whereas macrolides, and even more so fluoroquinolones, easily reduce the original inoculum. PMID- 1864272 TI - Activity of antibiotics against Staphylococcus aureus within polymorphonuclear neutrophils. AB - The intracellular location of certain strains of Staphylococcus aureus serves as a reservoir of bacteria which is thought to be important in therapy of recurrent infections in humans and in chronic staphylococcal mastitis in dairy cows. This overview summarizes data pertaining to the intracellular survival of Staphylococcus aureus within polymorphonuclear neutrophils (PMNs) both in vitro and in vivo in the face of antibiotic treatment. While compounds such as rifampin, clindamycin, erythromycin, and ciprofloxacin have been shown to be rapidly taken up by PMNs, the ability of antibiotics to concentrate within PMNs did not strictly correlate with their ability to kill intracellular Staphylococcus aureus. Rifampin and ciprofloxacin have been shown to be the most effective intraphagocytic killing agents, while clindamycin and erythromycin were inactive in these in vitro assays. In vivo, in therapy of Staphylococcus aureus arthritis and peritonitis in humans and in certain mouse models rifampin has generally been shown to be more effective than comparator antibiotics. In a staphylococcal subcutaneous abscess model, however, clindamycin was very effective in curing the Staphylococcus aureus abscesses in this system where PMNs were the primary inflammatory cells involved. The intracellular bacterial counts decreased as rapidly as the extracellular bacteria. Rifampin was also effective in the abscess model but ciprofloxacin was ineffective at the highest doses tested. The relevance of in vitro and in vivo models and the importance of PMNs as a reservoir of infection in staphylococcal diseases in humans and the dairy cow are discussed. PMID- 1864273 TI - Activity of antibiotics against microorganisms ingested by mononuclear phagocytes. AB - The data available on the activity of antibiotics against microorganisms ingested by mononuclear phagocytes are reviewed. The antibacterial activity of penicillins against Staphylococcus aureus is enhanced by human monocytes. This enhancement is possibly brought about by a peptidoglycan-degrading enzyme that is produced and secreted by monocytes. Aminoglycosides affect bacteria ingested by mononuclear phagocytes, but their intracellular activity is limited as compared with that of non-phagocytosed bacteria. Clindamycin, erythromycin, ciprofloxacin and rifampicin are effective against intracellular bacteria. The first three of these antibiotics do not show enhanced activity against phagocytosed bacteria, contrary to what might be expected from their high cell-associated concentrations. PMID- 1864274 TI - Effects of anti-infectious agents on polymorphonuclear neutrophils. AB - Polymorphonuclear neutrophils play a crucial role in host defences against infectious diseases. New trends in anti-infectious therapy require knowledge of the possible interactions between the drugs and the natural defence system. This overview summarizes some of the in vitro data on the effects of anti-infectious agents on neutrophils. The relevance for the clinical situation is discussed. PMID- 1864275 TI - The resurgence of group A streptococcal infections and their sequelae. PMID- 1864276 TI - In vitro susceptibility of Francisella tularensis to fluoroquinolones and treatment of tularemia with norfloxacin and ciprofloxacin. AB - The in vitro susceptibility of ten strains of Francisella tularensis to four fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin and pefloxacin) was investigated by determining the MBCs of these quinolones. The results were as follows (mean +/- SE): ciprofloxacin 0.13 +/- 0.03 mg/l, norfloxacin 0.24 +/- 0.07 mg/l, ofloxacin 2.16 +/- 0.78 mg/l and pefloxacin 0.51 +/- 0.50 mg/l. These concentrations can be achieved in clinical practice. In addition, four tularemia patients were treated with an oral regimen of 750 mg ciprofloxacin b.i.d. and one patient with norfloxacin 400 mg b.i.d. The fever experienced by these volunteers vanished within a couple of days and they were able to resume normal work one week after receiving the antibiotics without any relapses later. These in vitro and in vivo results show that orally administered fluoroquinolones are promising antimicrobial agents for the treatment of human tularemia. PMID- 1864277 TI - Evaluation of the adenosine triphosphate test in the diagnosis of urinary tract infection. AB - Determination by bioluminescence of the bacterial adenosine triphosphate (ATP) level in urine was evaluated as a method for detection of bacteriuria in 1126 women with symptoms of UTI and 530 attending for follow-up. Conventional urine culture was used as reference method. The criterion for bacteriuria was growth of greater than or equal to 10(5) cfu/ml, giving a prevalence of 0.60. ATP levels of less than 10 nmol/l and greater than 50 mmol/l indicated abacteriuria and bacteruiria, respectively, whereas intermediate concentrations required culture if the nitrite test was negative. With this diagnostic strategy the sensitivity and specificity was 0.96 and 0.90 at the first visit and 0.90 and 0.98 at follow up. With some methodological improvement the ATP test could be useful in medium sized and small laboratories. PMID- 1864278 TI - Western blot analysis of immunoglobulin G antibodies to pneumococcal protein antigens in healthy adults. AB - Using the Western Blot technique, sera from apparently healthy individuals were shown to contain antibodies against pneumococcal protein antigens of different molecular weights. A remarkable correlation was found to exist between the number of protein bands stained and the level of antibodies to type-specific carbohydrate antigens and C-polysaccharide. The findings suggest that the presence of antibodies against protein antigens reflects past infection with pneumococci. PMID- 1864279 TI - In vitro synergistic activity between meropenem and other beta-lactams against methicillin-resistant Staphylococcus aureus. AB - The in vitro activity of meropenem, a carbapenem antibiotic, combined with eight other beta-lactams against methicillin-resistant Staphylococcus aureus (MRSA) was tested. The MICs of these antibiotics alone ranged from 12.5 to 1,600 micrograms/ml for the 25 clinical isolates of MRSA studied. All combinations with meropenem exhibited marked synergy as determined by the checkerboard method. The MICs in combinations of meropenem with other beta-lactams were reduced to 1/4 1/64 those of the antibiotics alone. No antagonism was observed for any of the combinations of meropenem with other beta-lactams. Synergism between meropenem and cefpiramide was the highest among the combinations tested, the geometric mean of the fractional inhibitory concentration index for this combination being 0.237. This combination also demonstrated strong bactericidal activity, the MBCs decreasing to 1/16-1/64 of those for the agents alone. In terms of the fractional inhibitory concentration index, this was the most effective combination against MRSA highly resistant to meropenem alone with synergism for 85% (81/95) of the strains. In addition, synergism of imipenem with cephalosporins against MRSA was demonstrated. The affinity of meropenem and cefpiramide for MRSA penicillin binding protein (PBP) 2' was very low, and the combination of both antibiotics showed an additive increase in affinity for this protein, but not a synergistic increase. Thus, the mechanism of synergism did not seem to be related to affinity for PBP2'. It is possible that there is another factor besides PBP2' which increases the resistance that the combinations inhibit the unknown factor. PMID- 1864280 TI - Pharmacokinetics of meropenem compared to imipenem-cilastatin in young, healthy males. AB - Imipenem combined with cilastatin and meropenem was given as intravenous infusions of 1 g to eight young, healthy males on two separate occasions. Blood and urine samples were collected for up to 12 h. The terminal half-lives in plasma were 0.98 h and 1.11 h for meropenem and imipenem, respectively. The volume of distribution was smaller for meropenem than for imipenem (12.5 l and 14.4 l, respectively). The plasma clearance for meropenem was 188 (SD 31) ml/min and for imipenem 183 (SD 25) ml/min. Renal clearance was on average 139 (SD 24) ml/min and 135 (SD 11) ml/min, respectively. About 75% of the administered dose of both compounds was eliminated unchanged in urine. Non-renal clearance accounted for approximately 25% of the total clearance for both drugs. The kinetics of meropenem are very similar to those of imipenem given with cilastatin, and meropenem is as stable against renal metabolic degradation as imipenem combined with cilastatin. PMID- 1864281 TI - Antibacterial activity of pantoprazole and omeprazole against Helicobacter pylori. PMID- 1864282 TI - Phagocytes, antibiotics and intracellular parasites: are the experimental data clinically relevant? PMID- 1864283 TI - Impermeability to quinolones in gram-positive and gram-negative bacteria. AB - The initial step in the accumulation of fluoroquinolone antimicrobial agents is binding to cell surface components reduced by lowered pH and divalent cations. Uptake into gram-negative and gram-positive bacteria is by simple diffusion. Entry through the outer membrane occurs preferentially for most agents by the porin route but a second process using the self-promoted uptake pathway is active especially for more hydrophobic agents. Fluoroquinolones bind to vesicles of phospholipid which may be the initiating step in cross-cytoplasmic membrane diffusion. An active efflux system has been described in Escherichia coli with evidence supporting its presence in several other bacteria. Total upset is not altered by a resistant gyrase. Resistant isolates associated with reduced total quinolone accumulation due to lowered uptake have been described for laboratory mutants and clinical isolates. Most but not all of these have had alterations in outer membrane proteins. A functionally dominant resistance gene has been cloned from resistant Staphylococcus aureus and codes for a highly hydrophobic protein most likely membrane associated. This gene is expressed in Escherichia coli and specifies resistance especially to hydrophilic quinolones, possibly by altered accumulation. PMID- 1864284 TI - Newly documented antimicrobial activity of quinolones. AB - The improved antimicrobial activity of newer fluoroquinolones and novel applications recently found for the drugs already marketed are reviewed. Several new compounds are more active against gram-positive bacteria than the presently marketed fluoroquinolones. WIN 57273, the most potent compound in vitro on a weight basis, is 16 to 128 times more active than ciprofloxacin against various staphylococci, streptococci, Enterococcus spp., Corynebacterium spp., Listeria monocytogenes and Bacillus spp. BMY 40062, PD 117558, PD 127391, sparfloxacin, temafloxacin and tosufloxacin also show enhanced in vitro efficacy against these species. These drugs also possess increased activity against various anaerobes, notably Clostridium perfringens, Clostridium difficile and the Bacteroides fragilis group. Mycobacterium tuberculosis, rapidly growing mycobacteria other than Mycobacterium chelonae, and Mycobacterium leprae are often susceptible to quinolones displaying bactericidal activity which is potentially useful for curing difficult-to-treat mycobacteriosis. In addition, a number of new products, notably those containing a cyclopropyl group, are more active than reference fluoroquinolones against Mycobacterium leprae. Sparfloxacin, BMY 40062 and WIN 57273 compare favorably with older fluoroquinolones in the killing of intracellular Legionella spp., and several of the newer compounds have greater antichlamydial potency. Improved antibacterial activity has also been found against Mycoplasma hominis, Ureaplasma urealyticum, Acinetobacter spp. and Pseudomonas maltophilia. By contrast, the newer quinolones have similar or less activity against Pseudomonas aeruginosa and Enterobacteriaceae. Recently, pefloxacin, ofloxacin and ciprofloxacin were found to be active against protozoa, including Plasmodium spp., Trypanosoma cruzi and Leishmania donovani, but not against Toxoplasma gondii. In the near future, more specific research testing unusual pathogens may lead to the identification of quinolones with more selective activity. PMID- 1864285 TI - Synergy and antagonism of combinations with quinolones. AB - Combinations of fluoroquinolones with other antimicrobial agents have been extensively investigated. Combinations of fluoroquinolones with aminoglycosides, beta-lactams, imidazoles, macrolides and clindamycin infrequently show synergy against Enterobacteriaceae and gram-positive bacteria. These combinations rarely show antagonism. Combinations of rifampin with fluoroquinolones tested against Staphylococcus aureus have been reported to show synergy and antagonism, and in vitro results have not correlated with results of animal infection experiments. Against Pseudomonas aeruginosa combinations of antipseudomonas penicillins or imipenem with fluoroquinolones are synergistic for 20% to 50% of isolates in vitro and also are synergistic in animal models of infection, whereas combinations of aminoglycosides with fluoroquinolones rarely show synergy against Pseudomonas aeruginosa. Against anaerobic species such as Bacteroides fragilis combinations of fluoroquinolones with clindamycin, anti-anaerobic penicillins, cephalosporins or imidazoles are occasionally synergistic but usually indifferent. Ciprofloxacin and ofloxacin combined with antituberculosis agents have activity against Mycobacterium tuberculosis and atypical mycobacteria. In general, fluoroquinolones should be combined with other agents not to achieve synergy, which is extremely variable, but to provide activity against bacteria inadequately inhibited by the fluoroquinolones. PMID- 1864286 TI - Immunological aspects of new quinolones. AB - The effects of new quinolones on the immune system have been mainly studied in vitro. Despite some conflicting results due to variations in study methodologies, certain conclusions can be drawn. Clinically relevant concentrations of most quinolones seem to have no direct effect on isolated immune parameters such as phagocytic cell functions, lymphocyte proliferation, immunoglobulin production, gamma-interferon secretion and bone-marrow progenitor cell proliferation. In contrast, the production of certain cytokines (IL-1, IL-2) and colony stimulating factors by stimulated lymphocytes and splenocytes is enhanced in the presence of clinically achievable concentrations of the drugs. IL-2 production is also enhanced when higher concentrations of quinolones are added to stimulated lymphocytes. However, most other functions such as IL-1 and TNF production, and proliferation of lymphocytes and bone marrow progenitor cells are inhibited in vitro by concentrations of quinolones exceeding 50 micrograms/ml. In vivo studies on immunomodulatory effects of new quinolones are few and are generally in agreement with the in vitro findings. Only very high dosages administered to experimental animals cause suppressive effects, while therapeutic doses are usually not associated with measurable alterations in immune functions. Recent reports on stimulatory effects of therapeutic doses of ciprofloxacin on bone marrow myeloid progenitor cells in irradiated, neutropenic mice, warrant further investigations in experimental animals as well as in neutropenic and bone marrow transplant patients treated with the new quinolones. PMID- 1864289 TI - Potential role of fluoroquinolones in the treatment of bacterial meningitis. AB - The search for new antimicrobial agents in the treatment of bacterial meningitis is justified by a rate of mortality that currently remains unacceptably high and by the emergence of bacterial resistance. Because of their excellent in vitro activity against gram-negative organisms and good penetration into the cerebrospinal fluid, the new fluoroquinolones may have a potential role in the treatment of central nervous system (CNS) infections. Although there are few reports on the use of fluoroquinolones in treatment of patients with CNS infections, experience to date indicates that pefloxacin, the most intensively studied agent, and ciprofloxacin provide effective treatment for patients with meningitis caused by susceptible pathogens. Since they cannot be used in patients whose skeletal growth is incomplete, the place of the fluoroquinolones in the treatment of Haemophilus influenzae meningitis is obviously very limited. Neisseria meningitidis is still exquisitely sensitive to penicillin G and ampicillin, and there is thus no reason to replace these agents by fluoroquinolones, except when patients are allergic to beta-lactam agents, or when parental administration is impossible. A potential use of the new fluoroquinolones would be in the treatment of meningitis due to gram-negative bacilli, including Pseudomonas aeruginosa, and Acinetobacter. PMID- 1864287 TI - Pharmacokinetics of quinolones: newer aspects. AB - Differences in pharmacokinetic properties are emerging as important determinants in distinguishing among clinical uses of individual new quinolone antimicrobial agents. Selected data on pharmacokinetics, new pharmacokinetic studies, and pharmacodynamics are reviewed, with reference to norfloxacin, ciprofloxacin, ofloxacin, pefloxacin, enoxacin, fleroxacin, lomefloxacin, and other new quinolones. Considering pharmacokinetics, oral bioavailability is excellent (greater than 95%) for most quinolones. Differences in peak serum concentrations and beta-half-lives of elimination exist, however, and are reflected in up to ten fold differences in values of the area under the curve of serum concentration versus time for administration of similar drug doses. As suggested by high apparent volumes of distribution and low binding to serum proteins, penetration into many body tissues and fluids is favorable. Considering new findings, orally administered ciprofloxacin has been found to be absorbed primarily in the duodenum and jejunum. Studies also suggest this drug to be cleared by transepithelial elimination into the bowel lumen as well as by the renal route. Oral bioavailability of quinolones has been demonstrated to be in general good in ill as well as healthy subjects but is reduced on co-administration with magnesium- and aluminum-containing acids, sucralfate (which contains aluminum), or ferrous sulfate. Pharmacodynamic parameters, such as the relationship of serum concentrations and drug potency in vitro to clinical response and suppression of bacterial resistance, have been little studied and merit further investigation. PMID- 1864288 TI - Evaluation of quinolones in experimental animal models of infections. AB - Many discriminative experimental animal models of infection have been utilized in the evaluation of newer fluoroquinolones. In vivo efficacy of many of the newer agents has been shown in experimental models of meningitis, endocarditis, pneumonia, urinary tract infections, pyelonephritis, osteomyelitis, abscesses of various types, septic arthritis, gastroenteritis, salmonellosis, listeriosis, tuberculosis, syphilis, sinusitis, prostatitis and burn wound sepsis, among others. This review focuses on recent developments in a few selected areas. Although the limitations of animal model studies are well described, these results provide a rationale for the appropriate clinical usage of the newer fluoroquinolones in humans. PMID- 1864290 TI - Use of quinolones for treatment of ear and eye infections. AB - Malignant otitis externa is a severe, necrotizing infection of the external auditory canal which is sometimes fatal. The traditional antimicrobial treatment has usually been the combination of an antipseudomonal beta-lactam and an aminoglycoside, given intravenously for 4 to 8 weeks. Over 100 patients have been treated with a fluoroquinolone alone, most commonly ciprofloxacin given by mouth in a dosage of 750 mg b.i.d. for 6 to 12 weeks. About 90% of patients have been cured. Treatment with a quinolone has the advantage over older treatments that it can be given orally and has a low rate of side-effects. The ocular penetration of the fluoroquinolones has been studied in patients with unifected eyes. After the administration of a single dose of ciprofloxacin, pefloxacin, ofloxacin or norfloxacin, penetration into the aqueous humor, expressed as the ratio of the peak concentration in the aqueous humor to that in the serum, is about 20%. The penetration of ciprofloxacin into the vitreous humor, based primarily on the data from one report, is about 20%. The concentrations are likely to be higher after repeated doses or in the inflamed eye. Whether the concentrations achieved will be adequate for therapeutic or prophylactic purposes has not been determined. PMID- 1864291 TI - Role of quinolones in the treatment of bronchopulmonary infections, particularly pneumococcal and community-acquired pneumonia. AB - In view of their antimicrobial activity and pharmacological properties, fluoroquinolones should be suitable for the treatment of lower respiratory tract infections. The overall clinical success rate using enoxacin, ofloxacin, pefloxacin, and ciprofloxacin ranges from 81% to 89%. Despite relatively high MICs of the fluoroquinolones for Streptococcus pneumoniae, the clinical success rate of these drugs in pneumococcal infections is 91%, but the eradication rate of this pathogen is lower (73%). In addition, fluoroquinolones appeared to be as effective as standard antibiotic regimens for treatment of bronchopulmonary infections in most of the comparative trials reported. The new quinolones could be a good alternative for treatment of acute exacerbations of chronic bronchitis, especially if examination of the sputum reveals gram-negative pathogens. In community-acquired pneumonia, drugs other than quinolones seem indicated because of the limited efficacy of the new quinolones in the treatment of severe pneumococcal infections and the poor activity of these drugs against the anaerobic flora causing aspiration pneumonia. In contrast, new quinolones should be very suitable for treatment of nosocomial pulmonary infections due to gram negative pathogens. Quinolones used with or without erythromycin and rifampin, might be useful in the treatment of Legionnaires' disease. The role of these drugs in treatment of Chlamydia and Rickettsiae infections remains to be defined. PMID- 1864293 TI - Treatment of intra-abdominal infections with quinolones. AB - Intra-abdominal sepsis may be caused by intestinal bacteria or by skin bacteria. In the largest series of patients studied in trials of quinolones, anti-anaerobic drugs were included in the therapeutic regimen. Several small series have reported success without the concomitant use of anti-anaerobic drugs. The balance of evidence at present suggests that the quinolones referred to in this report should be supplemented with anti-anaerobic drugs in the treatment of peritonitis related to bowel disease. Quinolones alone have been highly effective in the treatment of peritonitis associated with chronic ambulatory peritoneal dialysis, spontaneous bacterial peritonitis and biliary sepsis. Notwithstanding this success, the potential for an anaerobic aetiology in biliary sepsis and bacteremia must be borne in mind. Lack of clinical efficacy may be associated with resistant bacteria including streptococci. Quinolones offer a relatively non toxic alternative in the management of intra-abdominal sepsis as well as being cost-saving since early discharge from hospital on oral medication is possible. PMID- 1864292 TI - Use of quinolones in the treatment of gastrointestinal infections. AB - Bacterial enteropathogens are responsible for between 40% and 80% of diarrheal illness depending upon the age of the persons affected and geographic areas where illness occurs. Antibacterial agents will shorten the illness associated with enteric infection caused by enterotoxigenic Escherichia coli, Shigella spp. and Campylobacter jejuni. These drugs also are effective in the therapy of certain clinical conditions (presumably because they are due to the same agents) which are characterized by moderate to severe diarrhea with one or more of the following: high fever, dysentery (passage of bloody mucoid stools), or high leukocyte counts in stools. Antimicrobial agents are also effective in the therapy of travelers' diarrhea. The quinolone drugs have several advantages in the management of bacterial diarrhea where strains causing illness from nearly all regions of the world will show general susceptibility: high concentrations are achieved in the intestinal lumen following oral administration and resistance development is unusual. A quinolone probably represents the optimal agent for therapy of bacterial diarrhea in adults in areas where trimethoprim-resistant enteric pathogens are common. PMID- 1864294 TI - Fluoroquinolones in the treatment of typhoid fever and the carrier state. AB - Typhoid fever remains an important public health problem throughout the world with a higher morbidity and mortality rate in the developing countries. Early establishment of the diagnosis and prompt initiation of treatment with chloramphenicol, ampicillin or trimethoprim-sulfamethoxazole is not necessarily followed by complete resolution of the infection. Between 1% and 6% of patients with typhoid fever become chronic biliary carriers of Salmonella typhi. These carriers are potential factors in the continued transmission of the disease. The increasing emergence worldwide of strains showing multiple resistance to the agents traditionally used in therapy has encouraged investigators to seek alternatives such as third generation cephalosporins and recently the new 4 quinolones, which have greater activity against Salmonella typhi including multi resistant strains. The fluoroquinolones seem to be the treatment of choice in those regions where resistant strains of Salmonella typhi are prevalent. PMID- 1864295 TI - Use of quinolones in treatment of prostatitis and lower urinary tract infections. AB - The newer quinolones, ciprofloxacin, enoxacin, fleroxacin, lomefloxacin, norfloxacin, ofloxacin and pefloxacin are highly effective antimicrobial agents against the majority of bacteria responsible for urinary tract infections and bacterial prostatitis. The pharmacokinetic properties of these agents after oral administration result in high concentrations in human urine, as well as in prostatic fluid and prostatic tissue. Ciprofloxacin, enoxacin and lomefloxacin produce the highest concentrations in prostatic tissue, followed by norfloxacin, ofloxacin and fleroxacin. More than 400 patients with chronic bacterial prostatitis have been treated with one of the newer quinolones in varying doses for 10 to 84 days. The results indicate a cure rate of approximately 70%, although the follow-up period is quite variable in these studies. Clinical trials of short-term (single dose vs three days) therapy with the newer quinolones conducted in women with uncomplicated lower urinary tract infections were reviewed. Although bacteriologic cure rates were high with single doses of ciprofloxacin, fleroxacin, norfloxacin, ofloxacin and pefloxacin, approximately one in five women with suspected uncomplicated lower urinary tract infection experience failure of single-dose therapy. In contrast, a three-day regimen with these agents is more effective than a single-dose in the treatment of uncomplicated lower urinary tract infections in women. PMID- 1864296 TI - Chlamydial infections and the quinolones. AB - Some of the newer fluoroquinolones may be suitable agents for the treatment of Chlamydia trachomatis infections and non-gonococcal urethritis. To date, small studies with both ofloxacin and fleroxacin appear to achieve cure rates of 85 100% for urethritis and cervicitis due to Chlamydia trachomatis. However, large well-designed clinical trials are required to determine the efficacy and acceptance of these and other fluoroquinolones in the treatment of patients with genital or respiratory syndromes due to chlamydiae or other bacterial pathogens causing infections with similar manifestations. PMID- 1864297 TI - Use of quinolones in pediatrics. AB - Compared to nalidixic acid, the new quinolones possess an enlarged antimicrobial spectrum, greatly enhanced bactericidal activity, and substantial pharmacokinetic advantages. Because their activity against streptococci is limited the quinolones presently available will never be included in routine regimens for children. Moreover, adequate pharmacokinetic studies are still lacking in pediatrics, and potential drug toxicity warrants further long-term monitoring. Nevertheless, various studies strongly suggest that there is no quinolone-induced cartilage toxicity in humans, and the results of published clinical trials with fluoroquinolones in pediatric patients show promising efficacy and safety. From a review of the available data it is concluded that use of the quinolones in children should be limited to specific infections which are usually caused by Pseudomonas aeruginosa, Staphylococcus aureus or Staphylococcus epidermidis, and are complicated by underlying pathologic or special conditions such as cystic fibrosis or urologic abnormality. In each case, careful monitoring to determine efficacy, potential adverse effects including drug-drug interaction and toxicity, and any emergence of bacterial resistance is mandatory. PMID- 1864298 TI - Use of quinolones in the immunocompromised host. AB - Immune deficiency generally leads to infections. Cancer chemotherapy, medical interventions and various investigational procedures are important factors in the development of infection. In recent decades, there has been a major change in most cancer centers in the etiology of bacterial infections occurring in the immunocompromised host, most infections now being caused by gram-positive organisms. This might be partly due to prophylactic use of agents effective against gram-negative bacteria. The quinolones are now widely used in the treatment of serious infections of the immunocompromised patient. Prophylaxis with quinolones is also practised in cancer centers. PMID- 1864299 TI - Role of quinolones in surgical prophylaxis. AB - The general principles involved in the use of chemoprophylaxis in surgery, the selection of patients at risk, and the choice of antibiotic agents are reasonably well established. While a good deal of data exist regarding commonly used prophylactic regimens, very little data are available on the role of quinolones in surgical prophylaxis. The literature dealing with this area is reviewed, and studies on the use of quinolones in biliary, colorectal, urologic, orthopedic and vascular surgery are discussed. The data suggest that generally the quinolones are as efficacious as the other antibiotics with which they were compared, and in the case of urologic surgery the results using quinolones were better than those in non-treated controls. Single-dose prophylaxis was regularly shown to be as effective as multiple dose regimens. Further clinical trial data are necessary before any firm conclusions can be drawn regarding the role of quinolones in surgical prophylaxis. PMID- 1864300 TI - Side-effects of quinolones: comparisons between quinolones and other antibiotics. AB - Fluoroquinolones are generally very safe antibiotics which do not cause serious or life-threatening adverse reactions. The most frequent side-effects are gastrointestinal reactions (nausea, dyspepsia, vomiting) and CNS reactions such as dizziness, insomnia and headache. Many of the more severe CNS reactions seem to be due to metabolic interaction with theophylline, especially when enoxacin is used. Of the potentially serious side-effects, photoxicity has been reported in varying frequencies with the different fluoroquinolones. Caution is necessary when this group of drugs, especially pefloxacin, is prescribed to patients who will have intensive exposure to UV light during treatment. The finding in juvenile animals of cartilage damage after administration of high doses have resulted in recommendations that fluoroquinolones should not be used in children. Carefully monitored studies should be performed in paediatric patients to assess whether there is a real risk of such adverse reactions. PMID- 1864301 TI - Post-marketing surveillance of quinolones 1988-1990. AB - It has been much easier to obtain original data on adverse drug reactions (ADR) of quinolones from the pharmaceutical industry than it was two years ago. This is to be welcomed and, as anticipated, the new data continue to suggest that the new 4-quinolones have an ADR profile which is very similar to that of other antimicrobials. Visual disturbance is not a prominent feature, in contrast to the ADR profile of nalidixic acid. Better definition of quinolone ADRs requires prospective study, and the results of a newly completed prescription event monitoring study are awaited with interest. The potential use of computerised databases and record linkage is examined, but at present the number of quinolone prescriptions is too small to assess documentation of serious but rare events such as convulsions. Physicians need to be aware of the limitations of current data on suspected ADRs. Further investment in computerised databases is required to satisfy the requirements for attributing causality of an event to a drug. PMID- 1864302 TI - On the mechanism of mergocryptine-induced suppression of dopamine turnover in the rat striatum. AB - The effect of mergocryptine, a new ergot alkaloid, on the cerebral dopaminergic systems was examined using Wistar rats. The administration of mergocryptine (1 and 10 mg/kg i.p.) induced a significant suppression of striatal dopamine (DA) turnover. In vitro addition of mergocryptine (0.01-100 microM) induced a dose dependent suppression of the release of [3H]DA from striatal slices. Mergocryptine inhibited [3H]apomorphine binding to a striatal synaptosomal fraction, and its IC50 value was found to be 0.23 microM. Pretreatment with apomorphine (100 micrograms/kg s.c.) showed an additive effect on the mergocryptine (10 mg/kg)-induced suppression of DA turnover. These results suggest that mergocryptine may induce the suppression of striatal DA turnover by reducing DA release via the stimulation of presynaptic dopaminergic autoreceptors. PMID- 1864303 TI - Effects of brain natriuretic peptide on renin secretion in normal and hypertonic saline-infused kidney. AB - The effects of brain natriuretic peptide (BNP) on renin secretion were evaluated in normal and hypertonic saline-infused kidneys of anesthetized dogs. In the normal kidney (N = 5), intrarenal infusion of porcine BNP-(1-26) (pBNP) at a dose of 50 ng/kg per min attenuated the renin secretion rate significantly to 9 +/- 27% of control without exerting a significant effect on mean arterial pressure (MAP), renal blood flow (RBF) or glomerular filtration rate (GFR); urine flow (V) was significantly increased to 260 +/- 33% of control and urinary excretion of sodium (UNaV) to 480 +/- 140% of control. In the hypertonic saline infusion group (N = 6), intrarenal infusion of hypertonic saline (20% w/v) at 0.5, 0.8, and 1.0 mEq NaCl/min caused a decrease in GFR and natriuresis in a dose-dependent manner. The renin secretion rate was attenuated by hypertonic saline infusion (1 mEq NaCl/min) to 87 +/- 31% of control. In another group (N = 6), administration of pBNP at a dose of 50 ng/kg per min during hypertonic saline infusion (1 mEq NaCl/min) increased the renin secretion rate to 196 +/- 57%, increased RBF to 160 +/- 13%, increased GFR to 137 +/- 22%, increased V to 221 +/- 29%, and increased UNaV to 218 +/- 29% of the values measured during hypertonic saline infusion. Our results indicate that BNP inhibits renin secretion through sodium delivery to the macula densa and effectively inhibits the tubuloglomerular feedback response that is activated by intrarenal hypertonic saline infusion. PMID- 1864304 TI - Effects of dantrolene on the responses to methylxanthines in the isolated guinea pig trachea. AB - The effect of dantrolene on the responses to methylxanthines (caffeine and theophylline) and a beta-adrenoceptor agonist (salbutamol) was studied in isolated guinea-pig trachea. Caffeine and theophylline (1 microM-10 mM) and salbutamol (1 nM-10 microM) produced concentration-dependent relaxation of spontaneous and stimulated (acetylcholine 1 mM) tone. Responses to high concentrations (10 mM) of caffeine and theophylline added to tracheal strips either unstimulated (spontaneous tone) or indomethacin (2.8 microM)-treated were reversed to contractions in the presence of dantrolene (3 microM-0.3 mM). This effect was not observed for salbutamol or when relaxant responses to the agonists were generated in pre-contracted (acetylcholine 1 mM) strips. Dantrolene inhibited concentration dependently the contraction evoked by caffeine (1 mM) in indomethacin (2.8 microM)-treated strips at 20 degrees C. This effect of dantrolene was attenuated in a low Ca2+ (0.8 mM) medium or when the bath temperature was lowered to 10 degrees C. Although an intracellular site of action cannot be excluded these results suggest that dantrolene mainly interferes with transmembrane Ca2+ movements in the guinea-pig trachea. PMID- 1864305 TI - Effects of inhalation and intravenous anesthetic agents on pressor response to NG nitro-L-arginine. AB - The effects of anaesthetic agents on pressor effect of NG-nitro-L-arginine (L NNA), a potent inhibitor of nitric oxide (NO) synthesis, were examined in rats. I.v. bolus of L-NNA (1-32 mg/kg) in conscious rats dose dependently increased mean arterial pressure (MAP) to a maximum value of 53 +/- 2 mmHg at 16 mg/kg with ED50 value of 4.7 +/- 0.9 mg/kg. The effects of a single i.v. bolus dose (32 mg/kg) of L-NNA were examined in conscious rats and rats anaesthetised with pentobarbital, chloralose, ketamine, althesin (mixture of alphaxalone and alphadolone), urethane, enflurane or halothane. In conscious rats, peak MAP (51 +/- 3 mmHg) was reached 10 min after i.v. injection and the effect lasted more than two hours. The magnitudes of peak MAP differed under the influence of anaesthetic agents with the following rank order: althesin greater than conscious = pentobarbital = chloralose = ketamine = urethane greater than enflurane much greater than halothane (in which there was negligible change in MAP). The onsets were delayed in rats anaesthetised with pentobarbital, althesin, chloralose and enflurane but not altered with ketamine and urethane compared to that in conscious rats. Therefore, L-NNA caused intense and prolonged pressor response in conscious rats and rats anaesthetised with the i.v. anaesthetic agents pentobarbital, chloralose, ketamine, althesin and urethane. MAP effect of L-NNA was markedly attenuated by the inhalation anaesthetics halothane and enflurane. PMID- 1864306 TI - Inhibition of meal-stimulated gastric acid secretion by gastrin immunoneutralization in rats. AB - Gastrin 17-I was infused into conscious rats equipped with jugular and portal vein catheters and with a pyloric gastric drainage tube to achieve serum concentrations slightly higher than those found during intragastrically instilled peptone solutions. I.v. injected rabbit gastrin antiserum abolished gastrin 17-I stimulated gastric acid secretion in these animals. Gastrin immunoneutralization reduced peptone-stimulated gastric acid secretion by approximately 37% during the entire 30-min period of stimulation. Peptone-stimulated gastric acid secretion was only significantly (P less than 0.05) inhibited in the third 10-min period, but not in the first or second 10-min periods of stimulation. This study demonstrates that the late but not the initial period of peptone-stimulated gastric acid secretion is regulated by circulating gastrin in rats. PMID- 1864307 TI - Cocaine displaces [3H]WIN 35,428 binding to dopamine uptake sites in vivo more rapidly than mazindol or GBR 12909. AB - Previous studies have shown that [3H] WIN 35,428 binds preferentially to striatal cocaine receptors at the dopamine transporter after in vivo injection. In vivo binding competition studies were carried out to assess the relative rates of entry and occupancy of cocaine receptors by (-)-cocaine, mazindol and GBR 12909. After i.v. injection, (-)-cocaine occupied receptors relatively more rapidly than GBR 12,909 while mazindol was the slowest. PMID- 1864308 TI - Memantine is highly potent in protecting cortical cultures against excitotoxic cell death evoked by glutamate and N-methyl-D-aspartate. AB - The capacity of memantine to protect cultured cerebrocortical cells against N methyl-D-aspartate (NMDA)- and glutamate-induced cell death was examined. Excitotoxic cell death was evaluated by phase contrast microscopy and quantified by estimating the release of lactic dehydrogenase from damaged cells. Memantine showed a strong, long-lasting and concentration-dependent protective effect against the excitotoxic damage induced by glutamate and NMDA, with almost complete protection being attained at a memantine concentration of 0.1 mM. The present findings indicate that memantine has potential value as a drug against excitotoxic brain damage. PMID- 1864310 TI - Diurnal variation of nuclear volumes and the mitotic index of cells in the adrenal zona glomerulosa of rats. AB - In adult male Wistar rats (200-230 g), nuclear volumes of cells in the adrenal zona glomerulosa exhibit diurnal variation with the peak values at 12 p.m.-3 a.m. and the nadir value at 12 a.m. Diurnal variation of the mitotic index is characterized by high values from 9 a.m. to 6 p.m. and low values from 12 p.m. to 6 a.m. PMID- 1864309 TI - Biogenic amines and ascorbic acid in rat brain following steroid contraceptive treatment. AB - Chronic treatment with steroid contraceptive produced a decrease in dopamine and norepinephrine concentration in discrete brain areas and an increase in ascorbic acid level. We suggest that alteration in the level of biogenic amines by steroid contraceptive may have some functional correlation with the ascorbic acid concentration in rat brain. PMID- 1864311 TI - Nitrate-induced hypothyroidism is associated with a reduced concentration of growth hormone-releasing factor in hypothalamic tissue of rats. AB - Dietary nitrate significantly inhibits the growth of male and female rats. To test the possibility that the growth hormone-releasing factor (GRF) content in hypothalamic tissue is deranged under these conditions, male and female rats were fed a diet containing 3% KNO3 for 6 weeks, compared to a normal diet (4 X 5 animals). The food intake of rats fed nitrate was reduced significantly (23 and 28% resp.). Weight gain was also decreased by 35 and 41% in male and female rats. The mean Sm-C/IGF-I concentration was 1.61 and 1.03 rU/ml in male and female control rats, whereas the concentrations in nitrate-exposed rats were 0.92 and 0.64, respectively (P less than 0.01). The GRF content of hypothalamic tissue also decreased significantly from 407 and 533 ng/g protein in controls to 174 and 229 in treated male and female rats. Nitrate exposure is characterized by hypothyroidism, food intake depression, low Sm-C/IGF-I concentrations in plasma and a decreased hypothalamic GRF content. Independent of the peripheral changes, the content of Sm-C/IGF-I in the brain remains constant. The results of the study demonstrate that thyroid hormone deficiency leads to an inhibition of GH axis already at the hypothalamic level. PMID- 1864312 TI - Altered ambulatory activity and related brain monoamine metabolism in genetically obese Zucker rats. AB - Feeding-related behavior and alteration of brain monoamine metabolism were examined in the male lean, and obese Zucker rats. Ambulatory activity of obese rats was reduced in the dark cycle. Dopamine (DA) and its metabolite, 3,4 dihydroxyphenylacetic acid (DOPAC), contents were significantly decreased in the striatum of obese rats. However, the metabolic rate assessed with the DOPAC/DA ratio, and norepinephrine (EN) content were not changed in the striatum. Hypothalamic DA and NE contents were significantly reduced and the DOPAC/DA ratio was significantly increased in the hypothalamus of obese rats. The present findings suggest that the observed changes in brain monoamine metabolism may contribute to the development of obesity reducing ambulatory activity of obese rats. PMID- 1864313 TI - Effect of omeprazole-induced hypergastrinaemia on the proliferation of colonic mucosal epithelial cells in the rat. AB - In the present study we have investigated the effects of proglumide (PRO) and somatostatin analog (SMS 201-995) on the mitotic activity of colonic mucosa in rats under basal conditions and after omeprazole (OM). The stathmokinetic method was used. Proglumide and OM were administered for 5 days, twice daily, SMS 201 995 on the 5th day of the experiment only, also twice daily. It was found that: 1) OM enhanced the proliferation of colonic mucosa, as well as increased serum gastrin, when compared to controls, 2) OM and PRO, when applied jointly, decreased the mitotic activity of the colonic epithelium, 3) PRO alone increased the colonic cell proliferation. PMID- 1864314 TI - Mechanism for the cardiovascular action of intracerebroventricularly administered vasoactive intestinal polypeptide in rats. AB - It was investigated whether the secretion of epinephrine, norepinephrine, and arginine vasopressin from the adrenal medulla, sympathetic nerve endings, and posterior pituitary gland, respectively, was involved in the mediation of the pressor effect of intracerebroventricular (icv) administration of vasoactive intestinal polypeptide (VIP) in anesthetized rats. Icv administration of 1 microgram VIP increased mean blood pressure by 21% and heart rate by 17% in Wistar rats although the lesser dose was effective only for increasing heart rate. Simultaneously with the change in blood pressure and heart rate, the concentrations of plasma epinephrine and norepinephrine rose 4 and 10 min after VIP administration. After adrenalectomy, the action of VIP on mean blood pressure or heart rate was unchanged or partially reduced, respectively. Although the cardiovascular action of VIP was observed in control Long-Evans rats as well as in Brattleboro rats homozygous or heterozygous for diabetes insipidus, which hereditarily lacked vasopressin completely or partially, the increase in mean blood pressure after icv administration of VIP was more marked in homozygous than heterozygous rats or Long-Evans rats. These results suggest that the cardiovascular action of centrally administered VIP is mediated by increased sympathetic nerve outflows including stimulation of adrenal epinephrine secretion and is enhanced by the chronic absence of vasopressin secretion from the posterior pituitary gland. PMID- 1864315 TI - Hormone analytical and carrier protein alternations following administration of mifepristone (RU 486) for termination of early pregnancy. AB - Outpatient terminations were performed on 50 biochemically confirmed pregnancies of 33 to 43 days amenorrhea with a single oral dose of 600 mg of mifepristone (RU 486). 37 women were randomly assigned to an additional endocrine investigation, comprising serum levels of beta hCG, progesterone (P), estradiol (E2), cortisol (C), sexual hormone binding globulin (SHBG), and cortisol binding globulin (CBG) on days 0 and 7 prior to and following the drug administration. Of these 37 patients, 30 experienced a complete expulsion of the uterine contents, 28 until day 7, 2 subjects on day 9 and 10, respectively. The remaining 7 women either showed an unaffected pregnancy or the symptoms of incomplete abortion, which made a surgical intervention necessary. In the successfully treated cases the levels of beta hCG, P and E2 decreased significantly, the nonresponders showed unchanged or even increasing hormone values. No significant changes of cortisol concentrations were found in the group of nonresponders, while the successful cases exhibited a slight elevation probably due to the abortion-associated processes. No considerable therapy-dependent differences were observed in the levels of SHBG. A small but significant decrease in the mean CBG value could be calculated in the group of responders. PMID- 1864316 TI - Plasma cortisol and prolactin response to insulin-induced hypoglycemia in neurosis. AB - Prolactin (PRL) and plasma cortisol response to insulin induced hypoglycemia were studied in 14 patients with various somatic and vegetative complaints of neurotic character and in 12 controls. In all examined subjects glucose level fell below 50% of basal values and below 2.2 mmol/l. Significant PRL and plasma cortisol response were present in all controls. Plasma cortisol increase in control group was at least 1.5 fold higher than basal values and the difference between basal concentrations and highest values after stimulation was at least 0.25 mumol. Individual peak of PRL values in group of controls was 1.8-10 fold greater than basal levels. In the group of 14 patients in 11 cases no PRL response to challenge was found and in 4 cases also plasma cortisol response was blunted. In two patients extremely exaggerated PRL reaction was found. Different PRL responses to insulin-induced hypoglycemia are probably a manifestation of different types of neurotransmitter metabolism breakdown. PMID- 1864317 TI - Exogenous and endogenous suppression of thyroid-stimulating hormone induces similar effects on thyroidal iodothyronines. AB - Thyroidal concentrations of T4 and T3 and the T4/T3 ratio were analyzed in the nodular and paranodular tissues from two groups of patients with suppressed TSH secretion. The first group consisted of 17 patients with nontoxic nodular goitre (NG), 8 of whom received long-term levothyroxine therapy to suppress TSH, while remaining 9 were untreated. The second group consisted of 10 patients with autonomously functioning thyroid adenoma (AFTA), in whom TSH secretion was suppressed due to the adenoma-induced increase in thyroid hormone concentrations. In nodular tissues of NG patients, thyroidal T4 and the T4/T3 ratio were significantly higher in treated than in untreated patients (0.34 +/- 0.05 vs. 0.15 +/- 0.02 mol T4/mol of thyroglobulin (Tg) and 10.9 +/- 1.2 vs. 5.2 +/- 0.7 respectively). Analysis of paranodular tissues of NG patients also revealed a higher T4/T3 ratio in treated patients (16.0 +/- 2.1 vs. 6.9 +/- 0.9), although thyroidal T3 and T4 concentrations in treated and untreated patients were similar. In AFTA patients, both T3 and T4 concentrations were higher in the adenoma than in paranodular tissues (0.14 +/- 0.04 vs. 0.02 +/- 0.005 mol T3/mol Tg and 1.08 +/- 0.32 vs. 0.26 +/- 0.06 mol T4/mol Tg), whereas the T4/T3 ratio was significantly higher in paranodular tissues (23.2 +/- 5.9 vs. 9.3 +/- 1.8). These results indicate that suppression of TSH induced either exogenously or endogenously results in an increase in the thyroidal T4/T3 ratio that reflects an increase in T4 and/or a decrease in T3 concentrations. These findings also support the notion that TSH preferentially stimulates thyroidal T3 production. PMID- 1864318 TI - A 25-year-old man with congenital hypothalamic hypogonadism and anorexia nervosa. AB - We report a case of anorexia nervosa in a man who had suffered hypogonadism from infancy. The study of the case adds an evidence to clarify roles of sex hormones in anorexia nervosa (Young, 1975). PMID- 1864319 TI - Saccade-related Purkinje cells in the cerebellar hemispheres of the monkey. AB - Extracellular single unit discharges of cerebellar Purkinje cells (P-cells) were recorded from the cerebellar hemispheres of two Japanese monkeys (Macaca fuscata) during spontaneous and visually guided eye movements. We found that saccade related P-cells, whose simple-spike (SS) discharge rates were modulated in close correlation with saccadic eye movements, were localized in fairly restricted areas in the hemisphere, mostly in Crus IIa with some in the deep folia of Crus I. P-cells located in simple lobules, superficial folia of Crus I or in Crus IIp did not change their discharge rate during voluntary eye movements. Fifty-five saccade-related P-cells recorded from Crus I and II showed modulation of SS discharge rate related to both spontaneous and visually triggered saccades, with the modulation closely time-locked to the saccades. Two thirds (37/55) of saccade related P-cells began to change their SS discharge rate 20-100 ms prior to the onset of saccades. The remaining one third (18/55) changed their activity approximately at the same time as the saccade onset. These saccade-related P cells did not show changes in activity during smooth pursuit eye movements, and we did not find any P-cells in the cerebellar hemisphere which showed changes of activity preferentially during smooth pursuit eye movements. In about half (26/55) of the saccade-related P-cells, the pattern of modulation prior to and during saccades was biphasic: increase-decrease or decrease-increase. The other half (29/55) showed monophasic increases or decreases. For a given P-cell, the discharge pattern during saccades was similar for saccades of all directions, though there was a preferred direction in the amount of discharge rate modulation. The present findings suggest that the cerebellar hemisphere (Crus I and IIa) plays an important role in the control of voluntary saccadic eye movements, in addition to other cerebellar cortical areas (flocculus and posterior vermis) which are known to participate in the control of saccades. PMID- 1864320 TI - The role of the claustrum in the bilateral control of frontal oculomotor neurons in the cat. AB - The effect of claustrum (CL) stimulation on the spontaneous unitary activity of ipsi and contralateral frontal oculomotor neurons, was studied in chloralose anaesthetized cats. A total of 205 units was bilaterally recorded in the medial oculomotor area, homologous of the primate "frontal eye fields"; 127 neurons were identified as projecting to the superior colliculus; for 33 of these last units stimulation of the ipsilateral CL provoked an excitatory effect lasting 10-25 ms and appearing with a latency of 5-15 ms; on 8 units the excitatory effect was followed by an inhibition lasting 100-250 ms. Ninety-eight of the 127 neurons were also tested through activation of the contralateral CL: 13 cells showed an excitatory effect lasting 10-35 ms and appearing with a latency of 20-50 ms. In three of the thirteen units the excitatory effect was followed by an inhibition lasting 100-150 ms. Complete section of the corpus callosum abolished the contralateral CL effect, suggesting the existence of a direct claustro contralateral oculomotor cortex pathway running through the corpus callosum. The results could support the hypothesis that the CL may play a role in the bilateral control of the visuomotor performance. PMID- 1864321 TI - Gastric afferents to the paraventricular nucleus in the rat. AB - Extracellular recordings were made from vasopressin (AVP) and oxytocin (OXT) secreting cells in the paraventricular nucleus (PVN) of the hypothalamus in rats anesthetized with urethane-chloralose to determine the effects of electrical stimulation of vagal gastric nerves and gastric distension on their activity. Electrical stimulation of gastric branches of the vagus nerves inhibited 5 and excited 10 of 32 phasically firing neurosecretory cells. Approximately one third of the phasically firing neurosecretory cells (9 out of 29 cells) were transiently inhibited by gastric distension; an effect which was completely abolished by bilateral cervical vagotomy. In contrast, gastric nerve stimulation excited 45 of 72 non-phasically firing paraventricular cells. Thirteen of 77 non phasically firing cells tested were excited by gastric distension. We conclude that there are some sensory afferent inputs originating from gastric receptors and transmitted by gastric vagal afferents which inhibit the activity of AVP secreting neurons in the PVN although other inputs excite the cells. Similar inputs also excite some of the putative OXT-secreting neurons in the PVN. PMID- 1864322 TI - Functional interactions among neurons in inferior temporal cortex of the awake macaque. AB - Functional interactions among inferior temporal cortex (IT) neurons were studied in the awake, fixating macaque monkey during the presentation of visual stimuli. Extracellular recordings were obtained simultaneously from several microelectrodes, and in many cases, spike trains from more than one neuron were extracted from each electrode by the use of spike shape sorting technology. Functional interactions between pairs of neurons were measured using cross correlation. Discharge patterns of single neurons were evaluated using auto correlation and PST histograms. Neurons recorded on the same electrode (within about 100 microns) had more similar stimulus selectivity and were more likely to show functional interactions than those recorded on different electrodes spaced about 250 to 500 microns apart. Most neurons tended to fire in bursts tens to hundreds of milliseconds in duration, and asynchronously from the stimulus induced rate changes. Correlated neuronal firing indicative of shared inputs and direct interactions was observed. Occurrence of shared input was significantly lower for neuron pairs recorded on different electrodes than for neurons recorded on the same electrode. Direct connections occurred about as often for neurons on different electrodes as for neurons on the same electrode. These results suggest that input projections are usually restricted to less than 500 micron patches and are then distributed over greater distances by intrinsic connections. Measurements of synaptic contribution suggest that typically more than 5 near simultaneous inputs are required to cause an IT neuron to discharge. PMID- 1864323 TI - Retroactive memory of a visual discrimination task in the rat: role of temporal entorhinal cortices and their connections. AB - It has previously been shown that the temporal and entorhinal cortices may be critically involved in memory. In Experiment 1, rats with either damage to the temporal cortex (TC), lateral entorhinal cortex (LEC), or the medial entorhinal cortex (MEC) were tested for retention of a preoperatively acquired simultaneous brightness discrimination task. TC and LEC lesions impaired retention, whereas MEC lesions were without mnemonic effect. In Experiment 2, rats with either disruptions of the anterior neural connections of TC (TC/Ant), posterior connections of TC (TC/Post), or conjoint disruptions (Ant/Post) were tested for retention of the visual discrimination task. TC/Ant and Post/Ant lesions resulted in relatively mild, but significant memory impairment, whereas a profound effect was seen after TC/Post lesions. The results are discussed in terms of a very important role for LEC and its connections with TC in mnemonic function. PMID- 1864324 TI - Antidromic identification of midbrain near response cells projecting to the oculomotor nucleus. AB - Medial rectus motoneurons carry both conjugate and vergence eye position signals. Abducens internuclear neurons, whose axons travel in the medial longitudinal fasciculus, provide these motoneurons with the major signal for conjugate eye movements but not for vergence eye movements. A vergence signal appropriate for these motoneurons is seen on the near response cells that are found in the mesencephalic reticular formation within 2 mm of the oculomotor nucleus. The goal of the present study was to determine if midbrain near response cells project to the medial rectus subdivision of the oculomotor nucleus. Near response cells were recorded in two trained rhesus monkeys with ocular search coils. A stimulating electrode was positioned within the medial rectus subdivision of the oculomotor nucleus. Twenty-eight near response cells were found that could be driven by single pulse microstimulation of the ipsilateral medial rectus subdivision. In all cases, antidromic activation was confirmed by collision testing. Attempts to antidromically activate midbrain near response cells from the contralateral medial rectus subdivision were unsuccessful. Most antidromically activated cells had a steady state firing rate proportional to vergence angle. One cell also showed burst activity during the vergence eye movements. Divergence cells were not antidromically activated. PMID- 1864325 TI - Calcium binding proteins and neuropeptides as molecular markers of GABAergic interneurons in the cat visual cortex. AB - In the cat visual cortex, almost all parvalbumin-positive cells are GABAergic, and about 80% of the calbindin D-28K-positive neurons are also GABA immunoreactive. About 37% of the GABAergic neurons contain parvalbumin and a smaller fraction (about 18%) contains calbindin. Furthermore, parvalbumin and calbindin are localized in two separate neuronal populations in the cat visual cortex, suggesting that two GABAergic populations can be distinguished, one containing parvalbumin and one containing calbindin. Double staining for parvalbumin and neuropeptides (CCK, SRIF and NPY), revealed no double-labeled cells, with the exception of a few SRIF- and parvalbumin-positive neurons. These results show that cortical GABAergic cells can be differentiated on basis of their calcium binding protein and neuropeptide immunoreactivity. PMID- 1864326 TI - Vocalization-correlated single-unit activity in the brain stem of the squirrel monkey. AB - The brain stems of 17 squirrel monkeys (Saimiri sciureus) were systematically explored for vocalization-related single-unit activity during calls electrically elicited from the periaqueductal grey. Of 12,280 cells tested, 1151 fired in relation to vocalization. Of these, 587 reacted to external acoustic stimuli and started firing after vocalization onset. As most of these cells were located in classical auditory relay structures, they probably represent auditory neurones reacting indirectly to self-produced vocalization due to auditory feedback. Seven cells reacted to acoustic stimuli but fired in advance of self-produced vocalization. These cells were located in the pericentral inferior colliculus, dorsal nucleus of the lateral lemniscus, dorsomedial to the ventral nucleus of the lateral lemniscus and immediately lateral to the central grey. They are probably engaged in tuning the auditory system to process self-generated sounds differently from external sounds. 261 neurones reacted to nonphonatory oral movements (chewing, swallowing) and started firing after vocalization onset. These neurones were widely distributed within the brain stem, with the highest density in the spinal trigeminal nucleus and medially adjacent reticular formation. The majority of these cells seem to react to proprioceptive and tactile stimuli generated by phonatory and nonphonatory oral activities. Some of them may exert motor control on muscles that come into play at later stages of phonation. 57 neurones reacted to nonphonatory oral movements but fired in advanced of vocalization onset. These neurones were located mainly in the trigeminal motor nucleus, nucl. ambiguous, reticular formation around these nuclei, parabrachial region and lateral vestibular nucleus. Their role in motor control seems to be related to specific muscles rather than specific functions. 100 of the vocalization-related cells showed a correlation with respiration. Expiration-related cells were found in and around the rostral nucl. ambiguous and in the reticular formation dorsal to the facial nucleus. Inspiration-related cells were located in the rostral and caudal nucl. ambiguous regions, ventrolateral solitary tract nucleus and the lateral reticular formation below the trigeminal motor nucleus. Most of these cells probably represent premotor neurones of respiratory muscles and laryngeal motoneurones of the cricothyroid and posterior cricoarytenoid muscles. Finally, a last group of cells was found that was unresponsive to chewing and swallowing movements, quiet breathing and acoustic stimuli, but changed activity during vocalization. 38 of them became active before vocalization and cricothyroid activity, and 101 afterward.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1864327 TI - Integration in descending motor pathways controlling the forelimb in the cat. 18. Morphology, axonal projection and termination of collaterals from C3-C4 propriospinal neurones in the segment of origin. AB - The morphology of single C3-C4 propriospinal neurones (PNs) including the cell body, dendritic tree, axonal trajectory and the pattern of projection and termination of axonal collaterals in the C3-C4 segments was investigated by intra somatic or intra-axonal injection of horseradish peroxidase. All the C3-C4 PNs could be antidromically activated from the lateral funicle in C6 and the lateral reticular nucleus but not from Th13. Another criterion was that they received monosynaptic excitation from corticospinal fibres in the contralateral pyramid. Twenty-four C3-C4 PNs were successfully stained. They were located in the lateral part of laminae VI-VIII except for two neurones which were located in lamina V and two in lamina IX. Five to eleven dendrites originated from the cell bodies and extended throughout laminae IV-VIII and even into the white matter in the transverse plane and up to 3 mm rostro-caudally. The axonal trajectory from the cell body was usually curved before reaching the lateral funicle. The bifurcation of the stem axon into a descending and an ascending branch was mostly observed in the white matter close to or at the border between the white and grey matter at the level of the cell body. The ascending and descending axonal branches maintained their location in the same part of the lateral funicle. Sixteen out of 24 stem axons gave off collaterals in the grey matter and/or in the white matter. One to five collaterals were given off from the axons in the grey matter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864328 TI - Pyramidal excitation in long propriospinal neurones in the cervical segments of the cat. AB - 1. The effect of stimulating the contralateral pyramid has been investigated with intracellular recording from 128 long propriospinal neurones (long PNs) in the C3 Th1 segments of the cat. Long PNs were identified by the antidromic activation from the Th13 segment. They were located in laminae VII-VIII of Rexed. Single pyramidal stimulation evoked monosynaptic EPSPs in 15/40 of the long PNs in cats with intact pyramid. In 15 other long PNs, a train of three to four pyramidal stimuli evoked EPSPs with latencies indicating a minimal disynaptic linkage. The remaining 25% of the long PNs lacked mono- or disynaptic pyramidal EPSPs. In a few cases longer latency excitation was observed. 2. The location of the intercalated neurones which mediate the disynaptic pyramidal EPSPs was investigated by making four different lesions of the corticofugal fibres: 1) at the border of the C5 and C6 segments, 2) at the border of the C2 and C3 segments, 3) at the caudal part of the pyramid; three mm rostral to the decussation and 4) at the level of the trapezoid body. Stimulation of the corticofugal fibres was made either rostral to lesion 3 (rPyr) in order to activate neurones in a cortico bulbospinal pathway or caudal to lesion 3 (cPyr) to activate neurones in a corticospinal pathway. In the former case, in one experiment, stimulation was made in the pyramid between lesions 3 and 4 (double pyramidal lesion). In case of cPyr stimulation, lesions 1 and 2 were added sequentially in order to investigate if the corticospinal excitation was mediated via C3-C4 PNs. All lesions were made mechanically, except lesion 2 which in some of the experiments was performed by reversible cooling. 3. Stimulation in the pyramid rostral to lesion 3 and in between lesions 3 and 4 evoked disynaptic EPSPs in the long PNs, which shows that they were mediated via reticulospinal neurones. Stimulation in cPyr after lesion 3 elicited disynaptic EPSPs, which remained after lesion 1 but were abolished after adding lesion 2. It is concluded that the disynaptic cPyr EPSPs were mediated via intercalated neurones in the C3-C4 segments. 4. When the disynaptic cPyr EPSP was conditioned with a single volley in nucleus ruber and/or in tectum, it was markedly facilitated, especially when the conditioned volley was applied simultaneously with the effective cPyr volley. The results show that the intercalated neurones in the C3-C4 segments receive monosynaptic convergence from cortico-, rubro- and tectospinal fibres. Stimulation in the lateral reticular nucleus (LRN) evoked monosynaptic EPSPs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1864329 TI - Response properties of the periodontal mechanosensitive neurons in the trigeminal main sensory nucleus of the cat. AB - Periodontal mechanosensitive units (PM units) were recorded from the trigeminal main sensory nucleus (Vms) of the cat. The receptive fields of PM units were arranged from mandibular to maxillary divisions dorso-ventrally. The majority of PM units were single tooth units responsive to the canine tooth. They were directionally selective and had sustained responses to pressure applied to the tooth. The optimal stimulus direction of maxillary and mandibular PM units when the canine tooth was stimulated was single and it was oriented predominantly in the caudio-medial or rostrolateral direction. The threshold intensity of canine tooth stimulation was less than 0.05 N in most of the units. These findings indicate that the response properties of PM units in the Vms resemble fairly closely those of the primary afferent nerves arising from the periodontal mechanoreceptors. PMID- 1864330 TI - Control of extracranial and hindlimb blood flow by the midbrain periaqueductal grey of the cat. AB - Microinjections of D,L homocysteic acid (DLH, 40 nmoles) made in the lateral PAG of the unanesthetized and paralyzed decerebrate cat evoked distinct patterns of extracranial and hindlimb blood flow. One pattern, evoked from the pretentorial part of the lateral PAG (A3.3-A2.5), consisted of an extracranial vasodilation associated with an iliac vasoconstriction. Another pattern, evoked from the subtentorial part of the lateral PAG (P0.2-P0.9), consisted of an extracranial vasoconstriction associated with an iliac vasodilation. Both patterns were associated with increased arterial blood pressure. These results indicate (i) that the PAG contains neurons regulating head and hindlimb vasculature, and (ii) that these neurons are viscerotopically organized, in the sense that different representations of the head and hindlimb are found at different rostrocaudal levels. The significance of the results is discussed in the context of our previous findings that different kinds of defense reactions are evoked from these same pretentorial and subtentorial PAG regions. PMID- 1864331 TI - The neural basis of the behaviorally relevant N1 component of the somatosensory evoked potential in SI cortex of awake monkeys: evidence that backward cortical projections signal conscious touch sensation. AB - Studies of touch intensity discrimination in monkeys have identified a component of the somatosensory-evoked cortical potential, N1, generated within 50 ms of the stimulus, that predicts their behavioral performance. This study employed multiple-electrode arrays with relatively high spatial resolution (0.1 or 0.2 mm spacing) to record laminar profiles of somatosensory-evoked potentials (SEPs), multiple unit activity (MUA) and current source-densities (CSDs) at several sites across the postcentral gyri of two awake monkeys. This high resolution laminar analysis strongly supports our earlier hypothesis based upon low resolution data that N1 is generated by synaptic excitation targeted specifically at the most superficial cortical layers I/II: (1) The excitatory nature of N1 was indicated by elevated MUA which was maximal in layer III and extended down to subcortical white matter where fiber activity exceeded prestimulus levels; (2) In addition to CSD analysis, the observation that N1 was maximally negative within 0.10 mm of the border between layers I and II verified the superficial site of N1 synaptic excitation regardless of conductivity boundaries near the pial surface. A review of the anatomical literature finds that the most likely inputs responsible for N1 activation are the "backward" cortico-cortical projections from secondary somatosensory areas to SI which in area 1 are the major source of sensory-related input that specifically terminates in layers I/II. We suggest, therefore, that backward projections are involved in the conscious process of touch sensation as it is signaled by N1. PMID- 1864332 TI - The effect of muscle vibration on human position sense during movements controlled by lengthening muscle contraction. AB - Muscle vibration studies suggest that during voluntary movement limb position is coded by muscle spindle information derived from the lengthening, antagonist muscle. However, these investigations have been limited to movements controlled by shortening contractions. This study further examined this property of kinesthesia during movements controlled by lengthening contraction. Subjects performed a horizontal flexion of the right forearm to a mechanical stop randomly positioned at 30, 50 and 70 degrees from the starting position. The movement was performed against a flexor load (1 kg) requiring contraction of the triceps muscle. Vision was occluded and movements were performed under three conditions: no vibration, vibration of the right biceps and vibration of the right triceps. The perceived position of the right forearm was assessed by instructing subjects to simultaneously match the right limb position with the left limb. Vibration of the shortening biceps muscle had no effect on limb matching accuracy. However, triceps vibration resulted in significant overestimation of the vibrated limb position (10-13 degrees). The variability in movement distance was uninfluenced by muscle vibration. During movements controlled by lengthening contraction, there is a concurrent gamma dynamic fusimotor input that would enhance primary afferent discharge. Despite this additional regulating input to the muscle spindle, it appears that muscle spindle information from the lengthening muscle is important for the accurate perception of limb movement and/or position. PMID- 1864333 TI - Effects of electrical stimulation of the thoracic spinal cord on bladder and external urethral sphincter activity in the decerebrate cat. AB - Electrical stimulation of the spinal cord above the sacral segments was used to produce coordinated micturition in the paralysed decerebrate cat. Stimulation of the superficial aspect of the dorsolateral funiculus (DLF) within the lower thoracic (T9-T13) segments produced a bladder contraction coordinated with decreased activity in the external urethral sphincter (EUS) branch of the pudendal nerve during which time fluid was expelled. In addition, a similar response was observed with DLF stimulation at the boundary of the L5/L6 segments. At the second cervical spinal segment, however, stimulation of a more lateral and ventral portion of the superficial spinal white matter was the only effective site for producing micturition. The spinal cord-evoked response was comparable to the micturition evoked by electrical stimulation of the pontine micturition centre (PMC) within the brainstem. A bilateral lesion of the dorsal columns (DC) and the dorsolateral funiculi (DLF) at the lower thoracic levels abolished reflex micturition evoked by bladder distension. However stimulation rostral to the lesion, within the PMC or thoracic DLF, continued to produce coordinated bladder and sphincter response during voiding. Stimulation caudal to the lesion produced a decrease in pudendal nerve activity but did not produce a void or bladder pressure change. This reduction in pudendal nerve activity could be abolished with a second lesion of the superficial DLF caudal to the stimulation site. It was concluded that stimulation of the thoracic dorsolateral funiculus activates both ascending and descending fibres which can influence the bladder and/or sphincter muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864334 TI - Measurement of light touch perception threshold by contingent negative variation. AB - An objective method developed to measure the threshold of light touch perception using contingent negative variation (CNV) is described. The light touch stimulus was a slight indentation of the skin produced through a displacement controlled stimulating probe (tip diameter of 2 mm). It was applied as the conditioning (S1) stimulus of the classical CNV paradigm of S1, S2, and R. To increase the CNV amplitude, the S2 stimulus was either a red or a yellow LED. The subjects were required to respond to only one of two by pressing a button. When the light touch stimulus was perceived, the CNV was recorded in all 19 healthy adult volunteers. In 14 of them, a systematic determination of the threshold of the ball of the thumb and index finger, thenar, hypothenar, face, shoulder, anterior thigh, foot dorsum and great toe ball, have been done. The thresholds of the light touch perception as defined by objective CNV measurement are very close to the results of the subjective psychophysiological determinations in normals. The amplitude of the averaged CNV (12 responses) started to decrease when stimulus intensity was reduced to the point that the subjects were able to perceive only a fraction of the presented touch stimuli. We believe, therefore, that the objective CNV determination of the light touch perception threshold is precise and sensitive enough to be used in research as well as in clinical applications. PMID- 1864335 TI - Torque vectors of neck muscles in the cat. AB - Anatomical texts describe the neck musculature without measurements of muscle locations or quantitative estimates of pulling actions (torques). This study is based on measurements in stereotaxic coordinates of cat neck muscle origins and insertions, and neck intervertebral rotation axes. Torque vectors in three dimensions were calculated for 14 pairs of dorsal and ventral muscles that insert on the skull or first cervical vertebra. Predicted torque vectors were in general agreement with qualitative statements in the literature. Biventer cervicis and the rectus capitis major, medius, and minor muscles act mainly to raise the head, and longus capitis acts almost exclusively to lower the head. Longissimus capitis, sternomastoid, and cleidomastoid act mainly to roll the head. Complexus acts about equally to raise the head and rool it. Splenius and occipitoscapularis have torque in all three coordinate directions. Torques were altered by changing the pitch of the head with respect to the neck. The calculated neck muscle torques did not correspond to previously reported directions of neck muscle excitation during the vestibulocollic reflex. The neck musculature appears to be a complex, multidimensional system that presents interesting problems in motor control. PMID- 1864336 TI - Motion processing for saccadic eye movements in humans. AB - 1. We studied the latencies and amplitudes of saccades to moving targets in normal human subjects. Targets underwent ramp or step-ramp motions. The goal was to determine how the saccadic system uses information about target velocity. 2. For simple ramp motion saccadic latency decreased as target speed increased. A threshold distance model, which assumes that the target has to move a minimum distance before saccadic processing starts, provided a good fit to the responses of all four subjects and explains discrepancies between previously published findings. 3. A double step experiment showed that target position may have some effect on saccadic amplitude when sampled approximately 70 ms before saccade onset, but it must be sampled at least 140 ms before onset for an accurate saccade to occur. 4. Saccades to simple ramp targets approximated the target position 55 ms before saccade onset. Based on our double step results, this is more compensation than possible by a simple position estimate and implies extrapolation of target motion by the saccadic system. The lack of complete compensation may be due to an underestimate of the target speed and/or of the saccadic latency. 5. A delayed-saccade paradigm resulted in saccades with a longer, constant latency and allowed longer viewing of target motion. These saccades accounted for all but approximately 20 ms of target motion, suggesting that with more processing time of target motion a better extrapolation may be generated. 6. In a step-ramp paradigm the target stepped in one direction, then moved smoothly in the opposite direction. Saccades in this paradigm could be made in either the direction of the step or in the direction of target motion: the direction and latency were determined solely by the time at which the target crossed the fixation point. This time must be calculated from target speed and position, implying that the saccadic system must use speed information to adjust latency or to cancel unnecessary saccades. PMID- 1864337 TI - Reorganization of activity in the supplementary motor area associated with motor learning and functional recovery. AB - The supplementary motor area (SMA) of primates has been implicated in the initiation and execution of limb movements. However, when a motor task was extensively overlearned, few SMA neurons, if any, were active before the movement onset. Subsequent lesions of the primary motor cortex gave rise to the appearance of premovement activity changes, indicating usedependent reorganization of the neuronal activity in SMA. PMID- 1864338 TI - Tonically discharging neurons of monkey striatum respond to preparatory and rewarding stimuli. AB - The behavioral relationships of 396 striatum neurons with regular, tonically elevated discharge rates were studied. While monkeys performed a delayed gonogo task, neurons predominantly located in medial putamen responded with phasic depressions (n = 30) or activations (n = 5) to task-specific stimuli. Particularly effective was an instruction light preparing for movement or no movement reactions, and an auditory signal associated with reward delivery. Stimuli triggering arm or mouth movements were less effective. The data demonstrate that these usually poorly modulated neurons display context-dependent phasic activity in specific behavioral situations. PMID- 1864339 TI - Orientation bias of cat dorsal lateral geniculate cells: directional analysis of the major axis of the receptive field centre. AB - The receptive field centre of cells in the dorsal lateral geniculate nucleus were mapped as iso-sensitivity contours. 94% of the cells were found to have elliptical centres, and analysis of the major axis orientation showed that 29% and 59% of units had their major axis oriented within +/- 20 degrees of the radial and horizontal directions, respectively. The data for Y-cells showed a greater dispersion in their orientation biases (R = 0.57) compared with X-cells (R = 0.79). Nevertheless, a horizontal orientation bias was found in both classes of cells: 47% of Y-cells and 73% of X-cells. In addition, an examination of the major axis orientations was undertaken for cells with receptive field centres located along the radial direction of 35 degrees below the horizontal meridian. In this 35 degree Radial Group a horizontal bias was also confirmed. Analysis of the dispersion of major axis orientations with eccentricity from the area centralis showed a statistically significant decrease in scatter and, hence, indicated an increase in the horizontal bias with eccentricity. PMID- 1864340 TI - Obstructive lung disease in northern Sweden: respiratory symptoms assessed in a postal survey. AB - The prevalence of respiratory symptoms in 6,610 adults (3,372 men and 3,238 women); 35-36, 50-51 and 65-66 yrs of age, living in selected areas of Norrbotten, northern Sweden, were assessed in a postal survey. Response rates were identical in men and women, and at least one respiratory symptom was reported by 41% of each sex. Twenty two percent reported sputum production, and 14% reported wheezing. Despite differences in smoking habits and in the different age groups, the prevalence of symptoms did not differ between the sexes, or between urban and rural areas. Symptoms were as common in people living in the rural interior as in the industrialized coastal area. Present or past history of asthma was reported by 323 (5.9%) subjects, whilst 234 (4.1%) subjects stated that they had chronic bronchitis or emphysema. Less than half of the subjects who reported attacks of breathlessness together with wheezing stated that they had at any time had asthma. Whilst the exact prevalence of had asthma. Whilst the exact prevalence of at any time had asthma and chronic bronchitis cannot be assessed from this postal survey, its results indicate that the prevalence of asthma may be higher in northern Sweden than has been reported from the south of Sweden. PMID- 1864341 TI - A population survey of respiratory symptoms in the elderly. AB - Reversible airways obstruction is not uncommon in the elderly, but may be overlooked because of the high prevalence of other disorders with a similar presentation. In a search for patterns of symptoms which might predict treatable airways obstruction, we carried out a survey of men and women aged 65 yrs and over. Postal questionnaires were completed by 2,161 subjects selected at random from the lists of three general practices. Almost 60% of the sample complained of one or more respiratory symptoms. Smoking was a more important risk factor than age, sex or social class, and was associated particularly with wheeze, morning phlegm and chest tightness on waking. Several groups of symptoms tended to cluster in the same individuals. The two most closely related were chest tightness and breathlessness in response to animals, dust and feathers. Responses to irritants tended to cluster according to the symptom produced (cough, breathlessness or wheeze) rather than the provoking stimulus (smoke, cold air, household chemicals or traffic fumes). There was no evidence for the existence of the "bronchial irritability syndrome" which has been linked with asthma in younger adults. The relationship of symptoms to respiratory function and bronchial reactivity will be reported in a further publication. PMID- 1864342 TI - Occupational dust or gas exposure and prevalences of respiratory symptoms and asthma in a general population. AB - The relationship of occupational airborne, exposure to respiratory symptoms and asthma was examined using a self-administered questionnaire in a cross-sectional survey of a random sample (n = 4,992 subjects) of the general population aged 15 70 yrs of Hordaland county, Norway. The response rate was 90%. Twenty nine percent of the population had a history of occupational dust or gas exposure, 5% reported having been exposed to asbestos at work, and 4% reported quartz exposure. A history of occupational dust or gas exposure was associated with morning cough, chronic cough, phlegm when coughing, breathlessness on exercise, occasional wheezing and a physician's diagnosis of asthma after adjusting for sex, age, smoking habits and urban-rural area of residence. The adjusted relative odds ratios for the respiratory disorders in subjects exposed to dust or gas ranged from 1.6-1.9. The population attributable risk of occupational dust or gas exposure for the respiratory disorders ranged from 11-19%. The study indicates that respiratory disorders are independently associated with occupational airborne exposure in a Norwegian general population sample. PMID- 1864343 TI - Relationships between lung function and physical characteristics in young adult black and white males and females. AB - The relationships of lung function to physical characteristics in young adults have not been adequately described for different gender-race groups in the United States. As part of a study of the effects of ozone exposure upon Black and White men and women, we measured lung volumes, expiratory flow rates, and airways resistance on a sample of 314 healthy 18-35 yr old nonsmokers. Regression analysis indicated that lung function was adequately described as a linear function of either height or sitting height in each of the four groups, and that while not always significant, gender and race differences in the height and sitting height coefficients were consistently present with those of males and Whites larger than those of females and Blacks, respectively. Lung volumes were frequently observed to be associated with body mass index as measured by Quetelet Index (weight.height.2). The best fitting gender-race specific multiple regression models including these terms and occasional age terms are presented. Two additional models are presented, one of which simultaneously adjusts for both gender and race, and the other of which adjusts for gender for a given race. Comparison of predicted values from our study to those of other studies suggests that the population samples from this study may be similar to those of other American populations reported upon by others. PMID- 1864344 TI - Hyperosmolarity-induced increases in airway responsiveness and late asthmatic responses. AB - Airway responsiveness to inhaled methacholine was assessed before and after bronchial challenge with ultrasonically nebulized hyperosmolar saline (UNHS), and these changes were correlated with the development of late asthmatic responses (LAR). Sixteen subjects with mild to moderate asthma had two consecutive methacholine challenges before and one after a cumulative-dose challenge with UNHS. Twelve of these subjects also had a single-dose hyperosmolar challenge to document the occurrence of LAR and determine if UNHS had a significant cumulative dose effect. If a LAR was observed, a control day without challenge completed the study. Responsiveness to methacholine was similar on the 2 baseline methacholine challenges with a provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) (mean +/- SEM) of 1.11 +/- 0.94 and 1.16 +/- 0.94 mg.ml.1 (r: 0.98). However, it was significantly increased after the inhalation of UNHS with a PC20 (mean +/- SEM) of 0.57 +/- 1.00 mg.ml.1 (p less than 0.001). Two subjects developed a late fall in forced expiratory volume in one second (FEV1) of 19 and 46% after hyperosmolar challenge. In this last subject, the LAR, not reproduced on the control day, was associated with a marked post-UNHS change in PC20, going from a baseline of 4.4 to 0.7 mg.ml.1 after UNHS. The % fall in FEV1 following the dose-response hyperosmolar challenge and the single-dose hyperosmolar challenge were not different, with mean values +/- SEM of 34.9 +/- 2.2 and 35.8 +/- 4.1, respectively, (p greater than 0.5). In conclusion, airway responsiveness to methacholine may increase following hyperosmolar saline inhalation, often unrelated to LAR. PMID- 1864345 TI - Role of simulated repetitive coughing in mucus clearance. AB - The role of repetitive simulated coughing on the clearance of gel mucus simulant was investigated in vitro, by using a simulated cough machine. The repetition of cough induced a significant increase (p less than 0.01) in mucus simulant clearance (139.3 +/- 78.7 mm) in comparison to a single cough (24.9 +/- 27.5 mm). Moreover, the increase in frequency of the repetitive coughing induced a marked and significant increase in mucus simulant clearance (75.4 +/- 51.1 mm and 139.3 +/- 78.7 mm at 0.1 Hz and 1.6 Hz frequency, respectively). A significant (p less than 0.05) correlation was observed between the percentage increase of clearance and both shear-thinning index (r = 0.62) and the thixotropic index (r = 0.63). These results suggest that the shear-dependent properties of mucus, associated with a repetitive coughing, may increase the efficiency of mucus clearance by air flow mechanisms. PMID- 1864346 TI - Lack of type II cells and emphysema in human lungs. AB - Ten surgically removed human lungs or lobes were studied, to assess the relationship between the abundance of type II alveolar epithelial cells and the degree of emphysema. Type II cell abundance (total number as well as percentage of the total parenchymal cell population) was determined in sections of randomly selected tissue samples of these lungs or lobes by using a type II cell specific antibody specific anti-lavage serum (SALS-Hu), which recognizes surfactant associated proteins. In these tissue samples we also determined the degree of emphysema with the aid of a number of morphometric parameters, destructive index (DI), mean linear intercept (Lm in mm), and the number of normal alveolar attachments on (pre)terminal bronchioles (normal AA.mm.1). We subsequently calculated the Spearman rank correlation coefficients (rs) between the abundance of type II cells and parameters for emphysema. We found a significant negative correlation between the percentage of type II cells and DI at tissue sample level (rs = 0.55; p = 0.02). We also calculated correlation coefficients between the abundance of type II cells and the degree of small airways disease in (pre)terminal and respiratory bronchioles (SADscore), lung function, age and smoking habits. The results suggest a role for type II cells in the pathogenesis of emphysema. PMID- 1864347 TI - Independent risk factors for cumulative recurrence rate after first spontaneous pneumothorax. AB - From 1975 until 1987, 122 patients without (Group I, mean age 34 yrs) and 20 with pre-existing lung disease (Group II, mean age 66 yrs) were treated for their first spontaneous pneumothorax. Mean follow-up was 5.2 yrs (max. 12.8 yrs). There were 32 chest X-ray verified recurrences, 72% occurring during the first 2 yrs. One, 5 and 10 yr cumulative recurrence freedoms +/- standard error in groups I and II combined were 85 +/- 3%, 75 +/- 4% and 69 +/- 5%, respectively. Using Cox regression analysis in groups I and II combined, pulmonary fibrosis, age greater than or equal to 60 yrs, and height/weight ratio were independent predictors of recurrence. Combinations of these risk factors identified four risk strata with 10 yr recurrence freedoms ranging from 83-0%. Independent predictors in group I alone were pulmonary fibrosis, age greater than or equal to 60 yrs, height/weight ratio, and nonsmoking, resulting in four risk strata with 10 yr recurrence freedoms ranging from 98-31%. Recurrences after first-time treated spontaneous pneumothorax showed a distinct time-related pattern and should accordingly be analysed as a time-related event. In both the total patient-population and in the group without pre-existing lung disease, independent predictors of recurrence were identified, which allowed the patients to be substratified into groups with widely different recurrence rates. PMID- 1864348 TI - Inflammatory cell response in bronchoalveolar lavage fluid after nitrogen dioxide exposure of healthy subjects: a dose-response study. AB - The combination of environmental chamber exposure and bronchoalveolar lavage (BAL) was used to study the effects of the common air pollutant nitrogen dioxide (NO2). Eighteen healthy nonsmokers were exposed to NO2 during 20 min in an exposure chamber during light bicycle ergometer work. All subjects were examined with BAL at least 3 wks before exposure, as a reference. The subjects were re examined with BAL, in groups of eight, 24 h after exposure to 4, 7 and 10 mg NO2.m.3 (2.25, 4.0 and 5.5 ppm), respectively. An inflammatory cell response was found after exposure to all concentrations. An increase in the number of lymphocytes in BAL fluid was observed after 7 and 10 mg.m.3 (p less than 0.05 and 0.02, respectively). An increase in the number of mast cells, that appears to be dose-dependent, was found after exposure to all concentrations. The proportion of lysozyme positive alveolar macrophages was elevated after exposure to 7 mg.m.3. The inflammatory mediators fibronectin, hyaluronan, angiotensin converting enzyme (ACE) and beta 2-microglobulin were unchanged by exposure. Due to the findings of inflammatory cell changes far below the peak exposure limits for work places in industrialized countries, 9-18 mg.m.3, the safety of these limits is questioned. Studies are in progress in our laboratory using BAL to evaluate the effects of repeated NO2 exposure. PMID- 1864349 TI - Effect of cytostatic agents on the number of alveolar phagocytes and the efficacy of ceftriaxone in an experimental murine lung infection. AB - Mice made monocytopenic and granulocytopenic by cyclophosphamide or monocytopenic by etoposide were infected by exposure to an aerosol containing Klebsiella pneumoniae. Eighteen hours later ceftriaxone was administered and three hours after that the experiment was ended. At the time of infection and at 18 and 21 h the numbers of alveolar macrophages and granulocytes in bronchoalveolar lavage (BAL) fluid were significantly lower in the cyclophosphamide-pretreated animals than in the controls. Furthermore, outgrowth of K. pneumoniae in the lungs was significantly stronger in cyclophosphamide-pretreated mice and a fourfold higher dose of ceftriaxone was needed to obtain the same antibacterial effect as in the controls. In the etoposide-pretreated mice the number of alveolar macrophages in BAL was not significantly lower than that in the controls, but the number of granulocytes was. Compared with the controls, there was no significant difference in the number of K. pneumoniae in the lungs, and the efficacy of ceftriaxone did not differ either. PMID- 1864350 TI - Changes in left ventricular ejection fraction during REM sleep and exercise in chronic obstructive pulmonary disease and sleep apnoea syndrome. AB - Nine patients, 4 with chronic obstructive pulmonary disease (COPD) and 5 with obstructive sleep apnoea syndrome (OSAS) were monitored during sleep, rest and exercise. Left ventricular ejection fraction (LVEF) was investigated using gated equilibrium 99mtechnetium ventricular scintigraphy during rapid eye movement (REM) sleep, during exercise, and during wakeful rest. Control wakeful rest periods used for comparison with a study state (either REM sleep or exercise) were always selected during the same circadian segment as that state. Myocardial stress thallium-201 scintigraphy was performed during, and 4 h after, exercise, and results were compared to a daytime rest period. Several patients had myocardial hypoperfusion despite a normal electrocardiographic (ECG) treadmill test. During REM sleep, all patients exhibited a significant change in LVEF (greater than 5%) compared to wakefulness. During exercise, 5 subjects increased their LVEF normally (greater than 5%) and 4 (1 COPD, 3 OSAS) decreased it. All patients had a similar change (increase or decrease) during REM and at maximal exercise. Our results suggest that REM sleep in COPD and in OSAS can produce a myocardial stress as great as that produced by exercise. We conclude that REM sleep, like exercise, is a state in which morbidity may become higher and that it may account for mortality in COPD and OSAS patients with compromised myocardial circulation. PMID- 1864351 TI - Two-compartment modelling of respiratory system mechanics at low frequencies: gas redistribution or tissue rheology? AB - The mechanical properties of the respiratory system are generally inferred from measurements of pressure and flow at the airway opening. Traditionally, these measurements have been related through a single-compartment model of the respiratory system. Recently, however, there has been considerable interest in modelling low-frequency respiratory mechanics in terms of two compartments, since this gives a much improved description of experimental data. In this paper we consider two classes of two-compartment models that are compatible with pressure flow relationships of air measured at the airway opening. One type of model accounts for regional ventilation inhomogeneity in the lung in terms of two alveolar compartments. The other type of model considers pulmonary ventilation to be homogeneous, while the tissues of the respiratory system are modelled as being viscoelastic. In normal dogs, the appropriate two-compartment model has been shown to be the viscoelastic model. In the case of abnormal physiology, however, one must invoke a model having both viscoelastic tissues and ventilation inhomogeneities. Additional experimental data are required in order to identify such a model, and to quantify these two phenomena. PMID- 1864352 TI - Pollen deposition in intrathoracic airways. AB - The pathophysiological mechanisms of pollen-induced asthma have until now remained unclear, because pollen particles have generally been considered too large to penetrate into the lower respiratory tract. Such grains are therefore believed to be unable to induce an immunological response in the lower respiratory tract. There is evidence, however, that a small percentage of large particles (20-30 microns) may penetrate into the peripheral areas of the lung. It also appears that small airborne units of less than 5 microns with the same antigenic activity as pollen, may contribute to inhaled allergen burdens. Pollen asthma probably results from a gradual cumulative effect of deposition of small amounts of allergen in lower airways, and is hence poorly correlated with daily pollen counts. PMID- 1864353 TI - Application of a new ventilator-multi-plethysmograph system for testing efficacy of surfactant replacement in newborn rabbits. AB - We applied a new ventilator-multi-plethysmograph system to evaluate the effect of surfactant replacement in newborn rabbits under well controlled, nearly physiological conditions characterized by normal ECG and adequate PCO2 in right ventricular heart blood obtained at the end of the experiment. Up to 10 animals were ventilated in parallel with a pressure-constant common respirator system. Using a working pressure of 4.9 kPa (50 cmH2O), we could adjust the pressure delivered to each animal within the range of 0.49-4.4 kPa (5-45 cmH2O), by changing the length of an open high-resistance tube constituting the outflow limb of the connection between the common ventilator tube and the tracheal cannula. Immature newborn animals obtained after 27.5 days gestation and ventilated for 30 min with a tidal volume of 8-10 ml.kg-1 had a mean +/- SD lung-thorax compliance of 4.2 +/- 1.1 ml.kPa-1.kg-1 (0.41 +/- 0.11 ml.cmH2O-1.kg-1) and PCO2 of 8.5 +/- 1.9 kPa. In littermates treated at birth with a large dose of natural surfactant (Curosurf, 200 mg.kg-1, compliance increased to 6.0 +/- 1.0 ml.kPa-1.kg-1 (0.68 +/- 0.10 ml.cmH2O-1.kg-1) (p less than 0.01) and PCO2 decreased to 6.9 +/- 1.2 kPa (p less than 0.01). Near-term animals, obtained at 30 days gestation and ventilated under similar conditions had a compliance of 7.2 +/- 0.9 ml.kPa-1.kg-1 (0.71 +/- 0.09 ml.cmH2O-1.kg-1) and PCO2 of 6.4 (1.2) kPa. Administration of surfactant (same dose as above) to these mature animals at birth had no adverse effects. PMID- 1864354 TI - Scoliosis as cause of pulmonary atelectasis. AB - We present a patients with persistent position-dependent productive cough and intermittent fever. He was first examined at 38 yrs of age. Chest X-ray showed a severe thoracic lordoscoliosis and an atelectasis of the right lower lobe. Bronchography revealed a total stenosis of the right lower lobe bronchus. Five years later had increased symptoms. Spirometry showed total lung capacity (TLC) 3.8 l (predicted value 6.7 l), forced vital capacity (FVC) 2.6 l (4.8 l) and forced expiratory volume in one second (FEV1) 1.7 l (3.9 l). Bronchoscopy demonstrated a smooth stenosis of the right lower lobe bronchus but the stenosis could be passed through with a brush. Computed tomographic scanning demonstrated compression of the right lower lobe bronchus and the atelectasis. After surgical removal of the right lower lobe, all symptoms disappeared. Histological examination of the right lower lobe revealed fibrosis and chronic inflammation. PMID- 1864355 TI - Pulmonary alveolar proteinosis: prolonged spontaneous remission in two patients. AB - Pulmonary alveolar proteinosis is a rare idiopathic diffuse airspace disease characterized by intra-alveolar accumulation of large quantities of lipoproteinaceous material, with preservation of the lung interstitium. The clinical course of pulmonary alveolar proteinosis is variable. Spontaneous resolution is known to occur in up to a quarter of the cases. We describe two patients with untreated pulmonary alveolar proteinosis who experienced complete clinical, functional and radiographic resolution. In follow-up periods of fourteen and six years, both patients have remained asymptomatic. PMID- 1864356 TI - Cyclosporin for a severe case of aspirin-induced asthma. PMID- 1864357 TI - Stark effect in P700, the primary electron donor of Photosystem I. AB - Quadratic Stark effect in CP1 pigment-protein complex was examined at low temperatures in the red spectral region. The Stark spectra of samples containing P700 in reduced form exhibit a strong negative band at 704 nm, which disappears on chemical oxidation of P700. The change in permanent dipole moment, delta mu, of P700 on electronic excitation estimated from these spectra was found to be between 4.7 and 7.7 Debye units. It is suggested to reflect the charge-transfer contribution to the excited state of P700. For antenna chlorophyll, delta mu approximately equal to 1 D was obtained in accordance with the data for monomeric chlorophyll. PMID- 1864358 TI - Sphingosine stimulates calcium mobilization in rat parotid acinar cells. AB - In fura-2-loaded parotid acinar cells, 50-200 microM sphingosine induced an increase in cytosolic Ca2+ ([Ca2+]i). When extracellular Ca2+ was chelated by EGTA, 50 microM sphingosine failed to increase [Ca2+]i, but 100 or 200 microM sphingosine induced a slight and transient increase in [Ca2+]i. The addition of LaCl3 to the medium resulted in the same effect as chelation of extracellular Ca2+. When cells were incubated in low Ca2+ medium containing sphingosine, and extracellular Ca2+ was subsequently added, a rapid increase in [Ca2+]i depending on the concentration of sphingosine was shown. In low Ca2+ medium, a slight increase in [Ca2+]i induced by high concentrations of sphingosine was not shown after the transient increase in [Ca2+]i elicited by methacholine. Inhibitors of protein kinase C, H-7 and K252a, did not mimic the effect of sphingosine on [Ca2+]i. These results suggest that sphingosine stimulates Ca(2+)-influx and further stimulates the release of Ca2+ from agonist-sensitive intracellular pools by a mechanism that is independent of protein kinase C. PMID- 1864359 TI - Reconstitution of active sucrose transport in plant proteoliposomes. AB - The proteins of purified plasma membranes from sugar beet (Beta vulgaris L.) leaf were solubilized and separated on a size exclusion column. The fractions eluted from the column were monitored by ELISA with antibodies directed to a putative sucrose carrier protein. The peak most reactive in ELISA was approximately 120 kDa, and yielded a 40 kDa peak after denaturation by SDS. The 120-kDa peak was recovered and used for reconstitution experiments with asolectin. Upon imposition of an artificial pH gradient and electrical gradient, the obtained proteoliposomes exhibited active transport of sucrose, but not of valine. The active transport of sucrose was inhibited by N-ethylmaleimide and HgCl2. PMID- 1864360 TI - Osmoregulation in Saccharomyces cerevisiae. Studies on the osmotic induction of glycerol production and glycerol-3-phosphate dehydrogenase (NAD+) AB - Production of glycerol and a key enzyme in glycerol production, glycerol 3 phosphate dehydrogenase (NAD+) (GPD), was studied in Saccharomyces cerevisiae cultured in basal media or media of high salinity, with glucose, raffinose or ethanol as the sole carbon source. At high salinity, glycerol production was stimulated with all carbon sources and glycerol was accumulated to high intracellular concentration in cells grown on glucose and raffinose. Cells grown on ethanol accumulated glycerol to a lower level but showed an increased content of trehalose at high salinity. However, the trehalose concentration corresponded only to about 20% of the glycerol level, and did not compensate for the shortfall in intracellular osmolyte content. Immunoblot analysis demonstrated an increased production of GPD at high salinity. This increase was osmotically mediated but was lower when glycerol was substituted for NaCl or sorbitol as the stress solute. The enzyme also appeared to be subject to glucose repression; the specific activity of GPD was significantly lower in cells grown on glucose, than on raffinose or ethanol. PMID- 1864361 TI - Comparative membrane locations and activities of human monoamine oxidases expressed in yeast. AB - Human monoamine oxidases A and B were expressed under the control of a galactose inducible promoter in Saccharomyces cerevisiae. The two MAO isoenzymes were found located in the yeast mitochondrial outer membrane, probably in different orientations as suggested by controlled proteolysis experiments. A high level of both human MAO-A or -B activities is measured in intact mitochondria without the need for any detergent solubilisation step. The substrate and inhibitor selectivities of the membrane-bound MAOs are highly similar to those of purified human enzymes. The level of MAO-B activity, however, is selectively lowered when bound to the membrane. PMID- 1864362 TI - A mouse brain cDNA encodes a novel protein with the protein kinase C phosphorylation site domain common to MARCKS. AB - We have isolated a mouse brain cDNA clone encoding a protein of 200 amino acids (Mr 20,165) with partial homology with MARCKS (myristoylated alanine-rich C kinase substrate). Two regions show similarity with MARCKS, one is the kinase C phosphorylation site domain which is supposed to bind calmodulin, and the other is the region near to the N-terminus, including the consensus sequence of myristoylation. It has a similar amino acid composition to MARCKS, but the content of alanine is not as high. It is distributed throughout the mouse brain, but the pattern is not identical with that of MARCKS. Both proteins may be members of a new protein family involved in coupling the protein kinase C and calmodulin signal transduction systems. PMID- 1864363 TI - Identification of a polypeptide bound to the beta region of the mouse r protein L32 promoter. AB - Studies have been initiated to identify the protein component(s) which interact with the beta regulatory region of the mouse ribosomal protein L32 gene promoter. By the combined use of the mobility shift assay and UV cross-linking, a factor specific for the upstream transcriptional control sequence of the beta region of the ribosomal protein L32 promoter has been detected in mouse L1210 nuclear extracts. A mutation (GT----TC at -71 to -70) in this sequence eliminates the binding. Beta factor is identified as a 55 kDa polypeptide by UV cross-linking. Addition of excess beta element (double-stranded oligonucleotide) to a cell-free transcription system reduces transcription of the ribosomal protein L32 gene. Our results provide evidence that the interaction between the beta element and the beta factor is involved in ribosomal protein L32 transcription. PMID- 1864364 TI - Identification and partial characterisation of a low Mr collagen synthesised by bovine retinal pericytes. Apparent relationship to type X collagen. AB - Bovine retinal pericytes (BRP) in culture synthesise a low Mr collagenous polypeptide which appears similar, but not identical, to bovine type X collagen and which we have called 'BRP collagen'. This polypeptide displays the following characteristics: (i) it is sensitive to digestion by bacterial collagenase and is resistant to pepsin digestion; (ii) it has an apparent Mr of 45 kDa (pepsinised form); (iii) it is recognised by specific antibodies to type X collagen using immunoblotting; (iv) it is present in the cell layer/matrix but not in the medium of pericyte cultures; and (v) it is not disulphide-bonded into higher Mr multimers. The latter two properties distinguish BRP collagen from bovine type X collagen. We have recently shown that pericytes calcify in vitro. We now report that this calcification is associated with an increased synthesis of BRP collagen. PMID- 1864365 TI - Cysteinyl-tRNA synthetase is a direct descendant of the first aminoacyl-tRNA synthetase. AB - The gene encoding the cysteinyl-tRNA synthetase of E. coli was cloned from an E. coli genomic library made in lambda 2761, a lambda vector which can integrate and which carries a chloramphenicol resistance gene. A thermosensitive cysS mutant of E. coli was lysogenised and chloramphenicol-resistant colonies able to grow at 42 degrees C were selected to isolate phages containing the wild-type cysS gene. The sequence of the gene was determined. It codes for a 461 amino-acid protein and includes the sequences HIGH and KMSK known to be involved in the ATP and tRNA binding respectively of class I synthetases. The cysteinyl enzyme has segments in common with the cytoplasmic leucyl-tRNA synthetase of Neurospora crassa, the tryptophanyl-tRNA synthetase of Bacillus stearothermophilus, and the phenylalanyl tRNA synthetase of Saccharomyces cerevisiae. Sequence comparisons show that the amino end of the cysteinyl-tRNA synthetase has similarities with prokaryotic elongation factors Tu; this region is close to the equivalent acceptor binding domain of the glutaminyl-tRNA synthetase of E. coli. There is a further similarity with the seryl enzyme (a class II enzyme) which has led us to propose that both classes had a common origin and that this was the ancestor of the cysteinyl-tRNA synthetase. PMID- 1864366 TI - Isolation and nucleotide sequence of the extracellular acid protease gene (ACP) from the yeast Candida tropicalis. AB - The extracellular acid protease of Candida tropicalis was purified from the supernatant fraction of culture medium containing bovine serum albumin as nitrogen source and the NH2-terminal amino acid (aa) sequence of the protein was determined. The gene for the acid protease (ACP) was isolated using a pool of synthetic oligonucleotides as a probe and a segment of the deduced aa sequence was found to be in agreement with the NH2-terminal aa sequence of the protein. The deduced aa sequence of ACP is similar to the aa sequence of proteases of the pepsin family. The nucleotide sequence of the 5' portion of this gene revealed a coding sequence for a 60 residue propeptide containing two Lys-Arg amino acid pairs that have been identified as sites for peptidase processing of several exported peptides and proteins. The final Lys-Arg site occurs at the junction with the mature extracellular form of the acid protease. PMID- 1864367 TI - Effects of the lipase inhibitors, Triton WR-1339 and tetrahydrolipstatin, on the synthesis and secretion of lipids by rat hepatocytes. AB - The lipase inhibitors, Triton WR-1339 and tetrahydrolipstatin, were incubated with rat hepatocytes. Triton WR-1339 increased the recovery of triacylglycerol in the hepatocytes and incubation medium by 31% and 38%, respectively. Tetrahydrolipstatin decreased the accumulation of newly synthesized, and of total triacylglycerol in the medium. This compound might be useful in determining mechanisms involved in intracellular triacylglycerol metabolism and the secretion of very low density lipoproteins. PMID- 1864368 TI - Primary structure of bovine cathepsin S. Comparison to cathepsins L, H, B and papain. AB - The primary structure of bovine cathepsin S was determined by combining results of protein and peptide sequencing with the sequence deduced from nucleic acid sequencing. Using polymerase chain reaction (PCR) technology, cDNA clones commencing at amino acid 22 of the mature enzyme and continuing through the 3' untranslated region of bovine cathepsin S mRNA were isolated and sequenced. The open reading frame in these overlapping clones correctly predicts the determined amino acid sequence of 13 tryptic peptides derived from purified bovine spleen cathepsin S. The deduced amino acid sequence shows that mature bovine cathepsin S consists of 217 amino acids corresponding to a molecular weight of 23.7 kDa. Cathepsin S belongs to the papain superfamily of lysosomal cysteine proteinases and shares 41% identity with papain. Amino acid sequence identities of bovine cathepsin S to human cathepsins L, H, and B are 56%, 47% and 31% respectively. PMID- 1864369 TI - Cloning, overexpression, purification and crystallisation of ribosomal protein L9 from Bacillus stearothermophilus. AB - The cloning, sequencing and overexpression of the gene coding for Bacillus stearothermophilus ribosomal protein L9 is described. The sequence corresponds directly to that presented for the protein itself by classical methods, differing at only a few amino acid positions. The purification and crystallisation of the corresponding L9 protein is presented. The crystals are isomorphous to those described for L9 obtained by conventional methods. PMID- 1864370 TI - The involvement of photosystem II-generated H2O2 in photoinhibition. AB - The involvement of H2O2 generated by photosystem II (PSII) in the process of photoinhibition of thylakoids with a functional oxygen-evolving complex (OEC) was investigated. The rate of photoinhibition was decreased to the rate of loss of activity in the dark when bovine Fe-catalase was present during the photoinhibitory illumination. Photoinhibition was accelerated for both Cl(-) depleted and Cl(-)-sufficient thylakoids when KCN was present to inhibit the thylakoid-bound Fe-catalase. We propose that these preparations become photoinhibited by reactions with H2O2 produced via oxidation of water by the Cl( )-depleted OEC and by reduction of O2 at the QB site when PSII is illuminated without an electron acceptor. PMID- 1864371 TI - Activation mechanism of rabbit skeletal muscle myosin light chain kinase. 5'-p fluorosulfonylbenzoyl adenosine as a probe of the MgATP-binding site of the calmodulin-bound and calmodulin-free enzyme. AB - 5'-p-fluorosulfonylbenzoyl adenosine (FSBA), an ATP-like affinity labelling reagent, reacted with rabbit skeletal muscle myosin light chain kinase (skMLCK) and its calmodulin complex in a site-specific manner. Reaction was dependent upon the presence of the adenosine moiety of FSBA, saturated with increasing FSBA, was inhibited by MgATP, and was accompanied by stoichiometric incorporation of [14C]FSBA. The kinetic constants describing the reaction were similar for skMLCK and its calmodulin complex: k3 = -0.040 min-1 and -0.038 min-1, and Ki = 0.18 mM and 0.40 mM, respectively. It is concluded that the MgATP-binding site on skMLCK remains accessible at all times and maintains a near constant conformation. PMID- 1864372 TI - The binding of [3H]R-PIA to A1 adenosine receptors produces a conversion of the high- to the low-affinity state. AB - Kinetic evidence for negative cooperativity on the binding of [3H]R-PIA to A1 adenosine receptors was obtained from dissociation experiments at different ligand concentrations and from the equilibrium isotherm. The dissociation curves indicate that there is an apparent ligand-induced transformation of high- to low affinity states of the receptor. At concentrations of 18.2 nM R-PIA or higher there was only found the low-affinity state of the receptor. In view of these results equilibrium binding data were analyzed by the usual two-state model (assuming that there is an interconversion between them) and by the negative cooperativity model employing the Hill equation. PMID- 1864373 TI - Autoimmune antigen Ku is enriched on oligonucleotide columns distinct from those containing the octamer binding protein DNA consensus sequence. AB - During purification of the AP1 complex from the T cell line MLA144 we enriched for a complex which bound to an oligonucleotide column containing the AP1 DNA consensus sequence and co-eluted with a fraction required for AP1 binding activity. This complex although co-eluting with AP1 binding activity had previously been determined to be non-specific in its DNA binding properties. Further investigation determined that the complex was a heterodimer of 85 and 70 kDa which was antigenically related to the autoimmune antigen Ku. It is important to be aware of the abundance and avidity of the Ku complex to bind oligonucleotide columns when purifying sequence specific binding proteins. PMID- 1864375 TI - Chondroitinases release acetylcholinesterase from chick skeletal muscle. AB - Bacterial chondroitinases (both ABC and AC types) release asymmetric and globular forms of AChE from chick skeletal muscle samples. Heparinases, however, including heparitinase I, fail to do so under different incubation conditions. These results do not support the direct implication of the heparin/heparan sulfate family of GAGs in the interaction of the different AChE molecular forms with the muscle ECM. GAGs of the chondroitin/dermatan sulfate group could however be involved, either directly or indirectly, in the attachment of the AChE collagen like tail to the muscle basal lamina. PMID- 1864374 TI - Changes in the kinetics of inositol transport during TPA-induced differentiation of HL60 cells towards monocytes. AB - When exposed to the phorbol ester TPA, HL60 cells undergo growth arrest and differentiate towards monocytes. During TPA-induced differentiation there was a 2.6-fold increase in the rate of inositol transport (Vmax), a 2.1-fold increase in intracellular inositol and a 1.5-fold increase in inositol lipid. An increase in the Vmax of inositol transport did not occur when the variant cell line HL60Ast3 was exposed to TPA, which has been shown in this cell line to induce growth arrest but not differentiation. This observation suggests that the change in inositol transport during HL60 monocyte differentiation is specifically associated with the process of cell differentiation as opposed to growth arrest. PMID- 1864376 TI - The primary structure of the Laburnum alpinum seed lectin. PMID- 1864377 TI - Sphingosine inhibits attachment of murine Lewis lung carcinoma cells to laminin and type IV collagen. AB - The effect of sphingosine (SPH) on the adhesive properties of Lewis lung carcinoma (3LL) cells was investigated using plastic precoated with the extracellular matrix proteins, laminin, fibronectin, or type IV collagen. Treatment of 3LL cells with SPH (0.5-10 microM) resulted in a dose-dependent decrease in the ability to bind to laminin and type IV collagen but had little or no effect on attachment to fibronectin. Phorbol 12-myristate 13-acetate (PMA) selectively enhanced attachment of 3LL cells to laminin and collagen. The inhibitory effect of SPH on attachment to both proteins was competitively antagonized by PMA. These results suggest that SPH acts as a negative effector for cell attachment to laminin and collagen, and that the cell attachment process to both proteins might be regulated in part by protein kinase C. PMID- 1864378 TI - Shuffled domains in extracellular proteins. AB - A comprehensive list of domains in extracellular mosaic proteins is presented. About 40 domains were distinguished by consensus patterns. A subsequent sequence database search recognized these domains in more than 200 extracellular proteins. The results point to a structural network, which may also represent the molecular basis for a complex coordination of various functions within the world of extracellular proteins. PMID- 1864379 TI - Site-directed mutagenesis reveals the importance of disulfide bridges and aromatic residues for structure and proliferative activity of human interleukin 4. AB - Mutant proteins (muteins) of human Interleukin-4 (IL4) were constructed by means of in vitro mutagenesis. The muteins were expressed in E. coli, submitted to a renaturation and purification protocol and analysed for biological activity. Exchange of the cysteines at either position 46 or 99 which form one of the three disulfide bridges resulted in a nearly complete loss of biological activity and an unstable protein. The exchange of tyrosine 124 also inactivated the protein, while a mutation of tyrosine 56 left some residual activity. Exchange of the other four cysteines or of the single tryptophane had smaller effects. PMID- 1864380 TI - Photoreversible antigen-antibody reactions. AB - A monoclonal antibody (Z1H01) for an oligopeptide carrying an azobenzene group, was prepared under conditions where the azobenzene group is in the trans form. The antibody bound the hapten peptide effectively when the hapten peptide is in the trans form (K = 5 x 10(7) M-1), but the antibody released the hapten under irradiation with UV light where the hapten is in the cis form. The antibody bound the hapten again, when the hapten reverted to the trans form after irradiation with visible light. PMID- 1864381 TI - Genes encoding peroxisomal enzymes are not necessarily assigned on the same chromosome of an n-alkane-utilizable yeast Candida tropicalis. AB - We have resolved eight chromosomal bands from an n-alkane-assimilating yeast, Candida tropicalis pK 233, by using contour-clamped homogeneous electric field gel electrophoresis (CHEF). From the results of hybridization of DNA probes of yeast peroxisomal enzymes--catalase, acyl-CoA oxidase, carnitine acetyltransferase, isocitrate lyase, malate synthase, acetoacetyl-CoA thiolase, and 3-ketoacyl-CoA thiolase--to Southern transfers of CHEF gels, these genes were proven not necessarily to be located on the same chromosome. This fact shows that the genes encoding the enzymes tested were not distributed to be cistronic, although simultaneous and inducible synthesis of peroxisomal enzymes occurred in harmony with the proliferation of peroxisomes, suggesting that their co-ordinated expression might be mainly regulated by certain trans-acting factors. PMID- 1864382 TI - Evidence for a ribosome-associated thiol protease cleaving wheat germ methionyl tRNA synthetase. AB - A wheat germ protease is responsible for Mr 105,000 methionyl-tRNA synthetase hydrolysis, generating two fragments of Mr 82,000 (harbouring the catalytic domain) and 20,000, respectively. Specificity of the protease was sought for using different kinds of protein substrates. It turned out that charged peptides were preferentially cleaved and that no proteolysis occurred when proteins were replaced by small synthetic substrates, harbouring target sites similar to those cleaved in proteins. The protease could be a ribosomal protein, since it remained associated to ribosomal structure, even after treatment by deoxycholate, Triton X 100, 800 mM KC1 and puromycin. Nevertheless, it was still active after ribonuclease treatment of the ribosomes. An identical protease activity was found in rat liver, but not in E. coli. PMID- 1864383 TI - Direct demonstration of enol-oxaloacetate as an immediate product of malate oxidation by the mammalian succinate dehydrogenase. AB - Rapid malonate-sensitive transitory formation of enol-oxaloacetate followed by slow ketonization of the product was observed after addition of malate to the mammalian succinate-ubiquinone reductase in the presence of electron acceptor. The initial rate of enol-oxaloacetate production was equal to that of malate oxidation. Oxaloacetate keto-enol tautomerase had no effect on the initial rate of enol-oxaloacetate production nor on the kinetics of malate oxidation; the enzyme drastically accelerated the ketonization of the product. The solubilized and partially purified membrane-bound flavine adenine dinucleotide-dependent malate dehydrogenase from Acetobacter xylinum catalyzed oxidation of L- and D malate without formation of enol-oxaloacetate as an intermediate of the reaction. PMID- 1864384 TI - Chlorophyll levels in the pigment-binding proteins of photosystem II. A study based on the chlorophyll to cytochrome ratio in different photosystem II preparations. AB - The chlorophyll levels in pigment proteins of photosystem II were investigated by using photosystem II preparations with different levels of complexity. Based on the assumption that there is 1 cytochrome b559 per reaction centre it has been found that oxygen-evolving complexes containing CP26 and CP29 bind 42 chlorophyll molecules. When CP26 and CP29 are stripped away, the resulting PSII cores bind 30 chlorophyll molecules while CP43-less cores bind approximately 18 chlorophylls. It is therefore concluded that CP47 and CP43 bind 9-12 molecules of chlorophyll a and the D1/D2 complex binds 6 chlorophylls. Taken together CP26 and CP29 bind about 12 chlorophyll molecules. PMID- 1864385 TI - The signal peptide of human preproendothelin-1. AB - Synthetic mRNAs were produced using either the complete coding sequence of a human preproendothelin-1 cDNA clone or a truncated form in which the portion encoding the first 17 amino acids, representing a putative signal peptide for insertion into the endoplasmic reticulum, was replaced with a methionine codon. The mRNAs were translated in vitro in the presence or in the absence of microsomal membranes. Protection from trypsin digestion demonstrated that the full-length polypeptide, but not the truncated form, could be inserted into the membranes. Sequence analysis revealed that membrane insertion is accompanied by removal of the first 17 amino acids. These results indicate that the first 17 amino acids of human preproendothelin-1 are a functional signal peptide which allows the protein to enter the secretory pathway. PMID- 1864386 TI - Photoaffinity labeling of dog pancreas microsomes with 8-azido-ATP inhibits association of nascent preprolactin with the signal sequence receptor complex. AB - Transport of bovine preprolactin into dog pancreas microsomes involves a microsomal protein which is sensitive to photoaffinity labeling with azido-ATP and which is distinct from the ATP-binding protein, immunoglobulin heavy chain binding protein. Here we addressed the question of what stage of preprolactin transport is affected. Thus a nascent presecretory protein which is related to preprolactin, termed ppl-86mer, was employed. Here we show that the nascent preprolactin did not become associated with the alpha-subunit of the signal sequence receptor complex after photoaffinity labeling of microsomes with azido ATP. Therefore, we conclude that the microsomal protein which is sensitive to photoaffinity labeling with azido-ATP acts prior to the signal sequence receptor complex. PMID- 1864387 TI - Smoking and arterial disease--news of the old enemy. PMID- 1864388 TI - Investigation of the vertebral artery in cerebral atherosclerosis. PMID- 1864389 TI - Minor asymptomatic carotid stenosis contralateral to carotid endarterectomy (CEA): our experience. AB - The authors report their experience from 1985 to 1988 with 75 consecutive patients affected by bilateral carotid artery stenosis in whom only one side was surgically treated and the other had a minor (15-45%) asymptomatic carotid stenosis. These patients have been followed for a period ranging from 10 to 50 months (mean follow-up 21 months) by clinical examinations and non-invasive investigations (Doppler CW, Duplex scanner). The non-invasive evaluation included assessment of haemodynamic data and characterisation of plaque morphology (regular vs. irregular or ulcerated surface, homogeneous vs. heterogeneous plaque). During follow-up eight patients died: two (2.6%) from acute myocardial infarction, four from stroke (5.3%), and two (2.6%) from other causes. Twenty five patients (33.3%) had neurological symptoms related to the unoperated side: and four suffered stroke (5.3%). Twenty-one patients had TIAs (28%) related to the observed side. During follow-up five out of 29 (17.2%) homogeneous and 20 out of 46 (43.4%) heterogeneous plaques progressed (p less than 0.01). With regard to the surface characteristics, nine out of 25 regular plaques progressed and only three patients (12%) had neurological events; 19 out of 34 (55.9%) irregular plaques showed a progression and 14 caused neurological symptoms. Fourteen ulcerated plaques (87.5%) progressed (p less than 0.01). Our experience suggests that the basic trend in the follow-up of patients with bilateral carotid artery disease, is that the contralateral unoperated lesion may evolve and become symptomatic. These symptoms are generally TIAs but five patients (4.3%) suffered from strokes related to the unoperated side, all without warning TIAs. PMID- 1864390 TI - Coagulation in aortofemoral bifurcation bypass grafting. AB - Few data are available on the pathophysiology of the coagulation system during aortic surgery. Cross-clamping of the aorta, intestinal eventeration and circulatory shock in ruptured aortic aneurysms are thought to cause coagulation disturbances and hyperfibrinolysis. A prospective study of several parameters of the clotting system, i.e. standard clotting tests, platelet count, indicators of fibrinolysis, inhibitors of the clotting cascade and proteases were measured perioperatively in aortobifemoral bypass grafts. Ten patients undergoing elective procedures and two emergency cases with ruptured aortic aneurysms were included. The standard clotting tests reflected the use of heparin. A similar course of ATIII, C1-inhibitor, alpha 2-antiplasmin, plasminogen and fibrinogen with a decrease during the operation and a return to almost normal values postoperatively, were due to intra-operative blood loss, haemodilution and a slight activation of the clotting cascade, as well as, hyperfibrinolysis. This observation was supported by the increased levels of euglobulin lysis and PMN elastase and the resultant increase in some fibrinogen degradation products, indicating non-specific proteolysis. These changes were more pronounced in the two emergency cases, except for the heparin induced changes in PTT and thrombin time. It is concluded that non-specific proteolysis may be an important factor in the pathogenesis of clotting disorders in surgery of the aorta. Further research is needed to discover the pathways of non-specific proteolysis and its prevention by protease inhibitors. PMID- 1864391 TI - Duplex scanning in the diagnosis of acute deep vein thrombosis of the lower extremity. AB - In a prospective study the value of duplex scanning in the diagnosis of acute femoro-popliteal thrombosis was compared to conventional contrast venography (CV) as a gold standard. A total of 126 legs in 117 patients suspected of having deep vein thrombosis (DVT) or pulmonary embolism (PE) were examined with both methods. CV and duplex scanning were diagnostic in 98.5 and 97%, respectively. Femoro popliteal thrombosis was present in 64 legs (prevalence 54%). The sensitivity and specificity of duplex scanning were 90.6% and 94.6%, respectively. A marked improvement in sensitivity from 83.3 to 97% and overall accuracy from 88.7 to 96% was noticed between the first and second half of the study period. Of the individual duplex criteria in the diagnosis of DVT, abnormal vessel wall compressibility was the most accurate. The Doppler measurements however allow evaluation of venous areas difficult to assess with B-mode and add discrimination between partial or total vein occlusion. Duplex scanning is more accurate compared to CV in grading the anatomical extent of thrombosis. Agreement between venography and duplex scanning was found in 75% of the vein segments, in about 20% CV suggested more thrombus formation compared to duplex scanning. Thrombus in the deep femoral vein was documented by duplex scanning in 24 patients including two cases of isolated deep femoral vein thrombosis. Venography failed to visualise the deep femoral vein with sufficient diagnostic accuracy in 88% of the patients vs. 8.5% with duplex scanning. Duplex scanning is an accurate non invasive test in the diagnosis of acute femoro-popliteal thrombosis and superior to CV in the detection of non-occlusive and deep femoral vein thrombosis. PMID- 1864392 TI - Popliteal-to-distal bypass grafts for limb salvage in diabetics. AB - Between January 1984 and August 1989, 117 diabetic patients with a palpable popliteal pulse but distal limb threatening ischaemia underwent 124 popliteal artery (or below) to distal bypass grafts. All grafts were intra-operatively monitored. The operative mortality was 0.8% and the 30 day primary patency 93%. Primary patencies at 1 and 3 years were 88.6 and 85.2%, respectively. The results of using the popliteal artery as the proximal graft inflow site in diabetes are comparable to other patient groups and to alternative more proximal inflow sites, but require a shorter length of vein graft with a shorter vein harvesting incision, avoid groin disection and result in a more peripheral operation. PMID- 1864393 TI - Forskolin impregnation of small calibre PTFE grafts lowers early platelet graft sequestration and improves patency in a sheep model. AB - Synthetic vascular grafts have a thrombogenic surface which plays a role in graft failure. Systemic pharmacologic interventions have been used to lower platelet sequestration onto the graft surface but are associated with side effects. In this communication we describe the results of a new therapeutic principle of applying forskolin, a powerful cyclic adenosine monophosphate stimulator (cAMP) to the inner surface of PTFE vascular grafts. The grafts were evaluated with Indium-III-oxine labelled platelets and by graft patency on 3 consecutive days after implantation at 1 month and 3 months. Forskolin significantly lowered early platelet sequestration onto the treated graft surface when compared with controls. Graft potency at 1 and 3 months was also significantly higher in the forskolin treated grafts. PMID- 1864394 TI - Gentamycin beads in the treatment of localised vascular graft infection--long term results in 17 cases. AB - Seventeen patients were treated by the implantation of gentamycin beads for localised Szilagyi type III prosthetic graft infection. Three patients had a pan prosthetic infection and half of the remaining patients were cured, but three of these died from other causes within 3 months. The mean observation time of the four survivors was 20 months (7-39 months). One of the seven patients, in whom the gentamycin beads failed, died of infection, giving a total mortality rate of 6% (1.5-29%). The remaining patients were cured after resection of the infected segment of the prosthesis at a mean follow-up of 22 months (8-37 months). PMID- 1864395 TI - Laser thermal angioplasty for early repair of anastomotic stenosis after lower extremity arterial reconstruction: initial experience. AB - Laser thermal angioplasty with a sapphire hot-tip Nd-YAG laser system was effectively used for five grafts with anastomotic stenotic lesions which occurred after femoro-popliteal arterial reconstructions. Stenotic lesions were detected by a combination of Doppler flow waveform analysis and ankle/brachial index measurement in 32 femoro-popliteal and five femoro-tibial arterial bypass grafts in the postoperative period. The laser probe used was 3 to 4 mm in diameter. There were no perforations of the arterial wall caused by thermal ablation, even with repeated pulses of 40 watts of laser energy for 3 s. Contact Nd-YAG laser thermal angioplasty using this rounded, 3-4 mm hot-tip facilitated effective widening of the lumen of the anastomotic stenotic lesion. All patients remain well at follow-up from 9 to 20 months after laser thermal angioplasty. PMID- 1864396 TI - Increased in-vitro incubation time of endothelial cells on fibronectin-treated ePTFE increases cell retention in blood flow. AB - Endothelial cell (EC) seeding is postulated as a mechanism of improving patency of small calibre vascular grafts. However, the majority of seeded cells are lost within hours following restoration of blood flow. We postulated that incubating EC in-vitro on a graft will improve adherence and resistance to the sheer stresses of pulsatile blood flow. Fibronectin-treated ePTFE (5 cm x 4 mm ID) seeded with Indium-111-labelled autologous canine EC (1.5 x 10(5) cells/cm2) were incubated for four different time periods; 90 min, 24 h, 72 h and 6 days. Incubated grafts were subjected to blood flow of 75 ml/min for 6 h, in a canine ex-vivo arteriovenous shunt circuit. EC retention during perfusion was studied by measuring gamma activity emitted by the grafts. Cell morphology of non-perfused control groups and perfused groups was compared using scanning electron microscopy (SEM). SEM of control grafts showed progressive EC spreading on the ePTFE surface for up to 72 h incubation. Gamma activity was significantly higher at 6 h perfusion in grafts incubated for 72 h (82 +/- 4%) and 24 h (63 +/- 6%) vs. 90 min (34 +/- 13%, p less than 0.05), and between grafts incubated for 72 h vs. 6 days (55 +/- 7%, p less than 0.05). Perfused grafts incubated for 72 h showed unaltered EC morphology on SEM, few cells remained on 90 min incubated grafts. We conclude that incubating EC on fibronectin-treated ePTFE for 72 h in vitro after seeding improves cell retention during blood flow. PMID- 1864397 TI - The use of an adjuvant arterio-venous shunt in prosthetic femoro-crural bypass. AB - In limb threatening ischaemia the use of a long prosthetic graft to the distal calf vessels may be the only alternative to a primary amputation. Patency rates in these situations are relatively poor and the use of an adjuvant arteriovenous fistula (AVF) at the distal anastomosis to increase the velocity of flow above the thrombotic threshold seems logical. We present follow-up of up to 8 years in a series of 80 consecutive reconstructions to the distal crural vessels using human umbilical vein with an adjuvant AVF. The mean age of the patients was 68.3 years and 12 (15%) were diabetic. The indication for surgery was limb threatening ischaemia in all cases; 41 (51.2%) for established necrosis and the remaining 39 (48.8%) for severe ischaemic rest pain. The mean ankle:brachial index was 0.23. The common ostium (CO) configuration of AVF was used in 50 cases (62.5%) and pre anastomotic in 30 cases (37.5%). The volume blood flow in 49 cases, measured peroperatively using an electromagnetic flowmeter, was 116 ml/min (+/- 62.5) with the shunt closed and 283 ml/min (+/- 132.2) with the shunt open (p less than 0.01, Student's t-test). Cumulative patencies of all grafts were 39% at 2 years and 29% at 4 years. The age of the patient and the type of AVF, common ostium or pre-anastomotic, had no significant effect on patency rates, but grafts under 70 cm in length had a cumulative patency at 2 years of 42.5% compared to 13.5% for those over 70 cm in length (p less than 0.01). Cumulative patencies were derived by life table analysis and compared using the log rank test. The size of the recipient vessels at the distal anastomosis is thought to be crucial to the outcome of these operations. An increase in velocity of flow produced by an AVF, increases the wall shear stresses at this site and may lead to an increased tendency for intimal hyperplasia. It may be possible to mitigate these effects by the use of additional surgical or pharmacological techniques and further studies are required. PMID- 1864398 TI - Popliteal venous aneurysms with or without pulmonary embolism. AB - Popliteal venous aneurysms are rare and are most often found in patients with pulmonary embolism suggesting that such aneurysms are thrombogenic. Only 16 cases have been found in the past and only a few of these patients were without thrombus or pulmonary embolism. In this paper three patients are presented of whom two showed signs of thrombus. Surgical resection was performed to prevent thrombosis with a successful result. The literature is reviewed and according to this and our own experience surgical resection under cover of anti-coagulation is recommended. Our surgical technique is presented. PMID- 1864399 TI - Renovascular hypertension secondary to renal artery aneurysm detected by captopril-renography. AB - A case is described of a renal artery aneurysm which presented initially as hypertension. A captopril-renogram suggested a renal artery stenosis although none was found on arteriography or at surgery. After resection of the aneurysm the captopril-renogram was restored to normal. PMID- 1864400 TI - An inflammatory abdominal aortic aneurysm presenting as bilateral hydroceles. PMID- 1864401 TI - Multiple congenital aneurysms of unknown origin. AB - A case is reported of an 18-year-old man with a syndrome of multiple aneurysms of unknown origin. Several interventions were necessary over a 30-year-period, mainly for haemodynamic reasons or compression. A review of the literature revealed seven similar cases, two of which had Ehlers-Danlos Syndrome. PMID- 1864402 TI - Surgical repair of primary aorto-jejunal fistula associated with non-specific inflammatory abdominal aortic aneurysm. AB - A 28-year-old man with aorto-jejunal fistula associated with primary saccular abdominal aortic aneurysm (AAA) was effectively treated by resection and replacement with polytetraflouroethylene graft. The aetiology was suspected to be a non-specific aortitis, a rare cause of aorto-enteric fistula. PMID- 1864403 TI - Buerger's disease. PMID- 1864404 TI - Clinical features of Buerger's disease. PMID- 1864405 TI - Endodontic therapy for an open apex-apexification or apexogenesis. PMID- 1864406 TI - Periodontal disease--a growing challenge. PMID- 1864407 TI - [Canal obturation. Analysis of 4 different techniques]. AB - The Authors evaluate four different techniques for root canal filling by means of a stereo-microscope analysis of extracted teeth sections. The results indicate that: 1) the single-cone technique shows poor apical seal; 2) the Mc Spadden thermomechanical condensation technique produces good apical seal but often causes overfilling; 3) the vertical condensation and 4) the lateral condensation of gutta-percha confirm their efficacy, nevertheless the Authors recommend the second one because it is easier and request shorter time of execution. PMID- 1864408 TI - [Functional velopalatal insufficiency. Therapeutic possibilities]. AB - The function of the soft palate is complex; it takes part in speech, swallowing, and masticatory mechanisms. Its pathology ranges from morphological deficits to functional ones; these are commonly due to a central nervous system damage. The clinical analysis is based upon examination and instrumental prove, and leads to an optimum choice between surgical and prosthetic solutions. The latter is the best one in terms of quick execution, low costs and future possibilities of improvement. PMID- 1864409 TI - [Topical infiltration of diclofenac sodium during extraction of impacted lower 3rd molars]. AB - Somministrations with topical infiltration of a FANS (Diclofenac sodium) based on a new therapeutic scheme, were carried on by the Authors. Reduction of postoperative compliances and no side or general effects were noted. PMID- 1864410 TI - [Dysgeusia in clinical practice. 1. Physiology]. AB - The anatomical basis of taste are discussed both in their peripheral and in central aspects. The perception is based upon four principal flavors; this happens by complex chemical interactions between peripheral receptors of papillae and the taste producing substances. The nervous stimulus flows through fibres of VII-IX-X cranial nerves up to the tractus solitarius nucleus; successive elaboration leads to the taste sensation, whose principal cortical site is the zone between Silvius and Rolando's sulcus. The distribution of the sensible zones for the fundamental flavors is presented. PMID- 1864411 TI - [Solitary cyst of the jaws]. AB - A clinical case of solitary cyst of jaws has been presented. The diagnosis of this pathology with only objective and radiological examination is not always easy. The Authors suggest the need to execute explorative operation. PMID- 1864412 TI - [Orthopedic surgery for edentulous malocclusion]. AB - The treatment of maxillary deformities in edentulous patients, with reference to tooth-bearing ones shows some differences concerning both the treatment planning and the surgical procedures. The Authors present in detail their way of planning the treatment and some expedients and modifications they apply to the usual surgical procedure in this special kind of maxillary deformities. PMID- 1864414 TI - [Dysgeusia in clinical practice. 2. Pathology]. AB - The various types of dysgeusia are discussed and a clinical classification is proposed. Dysgeusia are divided according to the modifications of the intensity of the perception: ipergeusia and ipogeusie/ageusia. The latter are the most frequent and important ones; they are divided in congenital ones, rapidly developing ones, and slow developing ones. A practical way to distinguish among the rapidly arousing ones is to consider the duration of the symptom. If it lasts more than a week the probabilities of an underlying serious illness grow, mainly of CNS. The slow onset ones are most commonly due to general metabolic alterations, among which diabetes, and to common habits, like smoking. PMID- 1864413 TI - [Lesions of the oral cavity during antineoplastic therapy]. PMID- 1864415 TI - [Ionizing radiation absorbed by the patient]. AB - The aim of this study is to evaluate the skin contact dose to which the patient is exposed during an endo-oral radiography using the long cone technique (paralleling technique) and the short cone technique (bisecting angle technique). Measures were taken in 50 dental X-ray units with a range of tension from 50 to 70 Kvs. Measures were taken using a calcium fluoride thermoluminescent dosimeter (CaF2:Dy). Data are expressed in uGy/mA.sec., divided in relation to the tension's values and the kind of technique used. This study reveals that the bisecting technique presents higher doses (2-3 times higher) than the long cone technique (paralleling technique). PMID- 1864416 TI - [Chronic ulceration of the oral mucosa. Description of a case]. PMID- 1864417 TI - [The importance of materials. The range of choice]. PMID- 1864418 TI - [Isotopy and multicorticality: two fundamental principles]. AB - Starting out from Oral Implantology pioneers, the Author comes down to the present situation, in an effort to show which values should be considered as the true ones. "Nothing new under the skies" is the Author's comment, when he examines all the techniques and materials presented as "new" for commercial purposes, whereas they are not new at all. To prove his statements he goes back to the work of some implantology pioneers, such as Formiggini, Perron Andres, Chercheve, Strock, Pasqualini, Muratori, Tramonte, Linkow and others. In going over their most remarkable techniques, he maintains that what is being proposed nowadays as brand new was actually done long ago. Only names are now different: the process now called fibrous osseointegration used to be named osteofibrosis, and what is now called osseointegration was known as complete ossification. In order to remove the great confusion now prevailing in the dozens of implant systems, as well as in implant philosophy itself, the Author maintains that good implantologists should follow two fundamental principles: 1) implants should be built in a great variety of sizes, in order to take full advantage of cortical bones. They should be multicortical, generally quadricortical, since they should rest on the sinus floor cortical bone, on the alveolar ridge, the palatal and the buccal cortical bones (this is true for the elements implanted in the upper arch and in the front-mesial arch).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864419 TI - [Immediate decontamination. Comparative ergonomic study]. AB - The standard procedures of decontamination between two patients were studied. As standards were chosen the OSHA's standards (Organization for Safety and Health Administration). The study was conducted by means of a "time and motion" analysis. The most important conclusions reached were: 1) it's impossible to complete the whole sequence in less than 10-15 minutes; 2) within this period one assistant didn't have any time to help the doctor at the chair; 3) consequently the doctor has to work alone for 10-15 minutes, unless a second assistant had been employed; 4) consequently, when we try to improve the decontamination, we need another assistant to make the work smoother, with a rise of the costs; 5) the systematic usage of the so called "barriers" is extremely time-wasting; 6) the only way to reduce the decontamination-time is the use of automatic devices, as the "Autosteril". PMID- 1864420 TI - [Modified Class II tunnel preparation]. AB - Tunnel preparations for restoration of Class II carious lesions in primary molars preserve the marginal ridge and minimize sacrifice of healthy tooth substructure. Materials with improved bonding to tooth structure and increase potential for fluoride release allow Class II restorations without "extension for prevention". PMID- 1864421 TI - [Tartar and periodontal disease--a cofactor in etiopathogenesis]. AB - Calculus may be considered as an aggregate of calcified deposits or deposits that are going to calcify in the oral cavity. From a topographical point of view calculus is classified in supragingival and subgingival calculus. Calculus is composed by inorganic (70-80%) and organic (20-30%) components. Calculus results from calcification of plaque and epithelial cells exfoliated from oral mucosae. Calcification phenomena (carbonic acid theory) are caused by a rapid fall down of salivary acidity when saliva springs out gland ducts. In fact in the mouth there is a lower pressure of carbon dioxide than in the gland ducts. From this fact results that calcium bicarbonate (dissolvable) becomes calcium carbonate (undissolvable) that forms, starting from nucleating particles, calcium carbonate crystals. Then calculus is one of the most important cofactors in the etiology and pathogenesis of periodontal disease: a) it favors plaque growth and stabilizes it to dental and periodontal tissues; b) it favors retention of food debris and hinders dental cleaning; c) it has endotoxins and lets them free slowly; d) it hinders periodontal recovery. From this study it results that scaling and root planing are one of the first steps in periodontal therapy. PMID- 1864422 TI - [Professional dental responsibility in HIV virus contagion]. AB - The Authors consider the forensic implications regarding the transmission of HIV to the orthodontic patient. First of all, the lesions of the oral cavity that require immediate diagnosis with foremost importance given to hygiene and prevention are examined. Secondly, the subject is considered of professional liability for virus transmission due to the physicians malpractice, particularly focussing on the possible fault, type of damage and cause-effect relationship. Sanctions are considered in detail regarding virus seropositivity and occurrence of symptomatology in the different phases of the disease, thus leading to a brief outline of possible refunding guidelines. Particular emphasis is placed on the evaluation of the causal relationship, underlying the difficulty related to establishing a clear cut cause-effect relationship. PMID- 1864423 TI - [Complete denture retention. New techniques]. PMID- 1864424 TI - [Forceps in tooth extraction. Method of use and working position]. AB - In the present paper the physical properties and the utilization of the surgical forceps has been explained. The correct working positions during dental extraction in different oral quadrants have been examined. PMID- 1864425 TI - [Esthetic restorations and occlusal stress]. AB - The purpose of this work is to value reconstructions on conoid, abraded and fractured elements made using an hybrid composite. Results have been excellent either functionally or aesthetically. PMID- 1864427 TI - Designed for growth. PMID- 1864426 TI - [Training and professional profile of dentistry in the EEC. 14]. PMID- 1864428 TI - This doctor wanted something "different". PMID- 1864429 TI - Planning a new facility? PMID- 1864430 TI - Treat your staff like real people. PMID- 1864431 TI - Color coding and computers. PMID- 1864433 TI - Recall system management--1. Check the health of your recall system. PMID- 1864432 TI - Licensure by credentials: still a chance? PMID- 1864434 TI - Maintaining preparedness for the life-threatening office medical emergency. PMID- 1864435 TI - [Insulin antibodies: methodology and clinical implications]. AB - Anti-insulin antibodies detection is based on the demonstration of a specific and saturable binding to insulin either radiolabelled with 125 I (Radiobinding assay or RBA) or coated on a solid phase (Enzyme linked immunosorbent assay or EIA). The 2 assays are remarkably different by their sensitivity to the affinity of the antigen antibody reaction. In addition, RBA may be biased by the presence of the iodine atom on the radioiodinated insulin whereas, at least on theoretical grounds. EIA could be biased because of denaturation or non availability of some epitopes when insulin is coated. Anti-insulin antibodies may be induced by insulin therapy. When they "spontaneously" appear, they are called autoantibodies. Insulin autoantibodies may be detected in the normal population, in type 1 diabetic patients before any administration of exogenous insulin and in patients suffering from the autoimmune hypoglycemic syndrome. In some patients, this syndrome may be associated with administration of a thiol containing drug. In some cases, insulin antibodies may appear several years after a transient insulin therapy, possibly as a consequence of a disturbance of the immunologic memory. The properties of antibodies and autoantibodies (concentration, affinity, number and nature of epitopes, heavy and light chain composition and ability to form aggregates) are relatively characteristic of the disease with which they are associated and determine their potential effects on insulin bioavailability and plasma glucose homeostasis. PMID- 1864436 TI - Risk/benefit ratio of changing late obstetrical strategies in the management of insulin-dependent diabetic pregnancies. A comparison between 1971-1977 and 1978 1985 periods in 389 pregnancies. AB - We compared the results of 166 pregestational insulin dependent diabetic pregnancies in the period 1971-1977 to those of 223 in the period of 1978-1985, after the introduction of self monitoring of blood glucose. During this second study period late obstetrical strategies changed to prolongation of pregnancy up to term, avoidance of final hospitalization and decrease of the rate of cesarean section. Maternal blood glucose control was less optimal in the second period resulting in a higher incidence of fetal macrosomia. Despite this, unexplained stillbirth disappeared, neonatal morbidity did not change significantly and the overall benefit was a reduction of preterm birth and a better quality of life for our patients. We conclude that the final hospitalization from week 32 onward in insulin dependent diabetic pregnancies is no more mandatory. PMID- 1864437 TI - Impaired glucose tolerance: influence by environmental and hereditary factors. AB - The influence on impaired glucose tolerance (IGT) by obesity, physical leisure time activity (PLTA), family histories of diabetes mellitus (DM) and other characteristics were evaluated in a health survey of 807 middle-aged females and males, with the rate of IGT 8.4% (WHO-criteria). Independent (adjusted for covariates) odds ratios concerning IGT were estimated. The ratios were 5.3 with the presence of obesity and 2.2. (ns) with low compared to high PLTA. In a subgroup of summarized environmental factors (obesity and low PLTA versus no obesity and high PLTA, n = 339), the independent odds ratio for IGT was 9.6 with obesity and low PLTA. With one 1st degree DM relative the odds ratio for IGT was 3.1. The ratio was increased both with the presence of relatives with non-insulin dependent diabetes mellitus and with the presence of relatives with insulin treated diabetes. Diabetic mothers yielded a higher ratio for IGT than diabetic fathers. In conclusion, the independent relative risk for IGT in this Swedish middle-aged urban sample was about two times higher with environmental factors (obesity only/obesity with low PLTA) than with one 1st degree DM relative. PMID- 1864438 TI - Blood pressure by 24 h ambulatory recordings in type 2 (non-insulin dependent) diabetics. Relationship to urinary albumin excretion. AB - The relationship between blood pressure and microalbuminuria, both associated with cardiovascular disease and death, is sparsely studied in Type 2 (non-insulin dependent) diabetes, and results may be interfered by the phenomenon of "white coat-hypertension". We therefore investigated blood pressure by 24h ambulatory recordings (oscillometry) and examined whether blood pressure related to the level of urinary albumin excretion rate (UAER) by synchronous 24h collections. Seventeen diabetics (50-75 years of age) with microalbuminuria (15 less than UAER less than 200 micrograms/min) (DM), 15 with normal urinary albumin excretion (DN) and 10 healthy controls (C) participated. All groups were of comparable sex, age degree of obesity and had normal serum creatinine, and the groups of diabetics were of similar known duration, glycemic control and frequency of antihypertensive treatment. Blood pressures measured at the clinic were significantly higher (p less than 0.01) than 24h recordings. An average systolic pressure of 142 +/- 11 mmHg in DN was increased (p less than 0.01) as compared to C: 130 +/- 10 mmHg, but no further increase was seen in DM: 146 +/- 19 mmHg. Diastolic pressures were not different among the groups (C: 77 +/- 8 mmHg, DN: 80 +/- 11 mmHg, DM: 79 +/- 9 mmHg). Average 24h systolic pressure correlated to the UAER r = 0.61, p = 0.009 in DM, whereas not in DN. By the present method we found isolated systolic hypertension in Type 2 diabetes which may express "vascular stiffness". There was, however, no further rise in blood pressure in patients with microalbuminuria, but in these patients albuminuria may be pressure dependent and/or expressive of vascular pathology. PMID- 1864439 TI - [Dyslipoproteinemia and diabetic nephropathy]. PMID- 1864440 TI - [Clinical and epidemiological features of diabetic patients followed under non specialized conditions]. PMID- 1864441 TI - Lectin-carbohydrate interactions in immunoregulation. PMID- 1864442 TI - Quantification of enzyme activities in brain sections by microphotometry. AB - 1. Catalytic enzyme histochemistry offers the possibility to demonstrate enzyme activities quantitatively (microphotometry) in brain sections of those sites where they are localized. 2. A prerequisite for quantification are appropriate histochemical procedures for the demonstration of enzymes, which are shortly discussed. 3. For the microphotometric determination of enzymes in brain sections the scanning microphotometry is at present the technique of choice. 4. This is described in the example of an image plane scanning system. 5. Using this technique two measuring procedures can be applied for the quantification of enzyme activities, i.e. kinetic and end-point measurements. 6. Methods for the microphotometric determination of certain important oxido-reductases and further enzymes are presented. 7. It is concluded that quantitative catalytic enzyme histochemistry could be a source of results complementary to those provided by conventional biochemistry. PMID- 1864443 TI - Liver ferrochelatase from normal and hexachlorobenzene porphyric rats. Mechanism of drug action. AB - 1. The action of hexachlorobenzene (HCB) on hepatic ferrochelatase was investigated. 2. A direct action of HCB, pentachlorophenol, porphyrins and haem on this enzyme activity was discarded. 3. In HCB porphyric liver there is probably an activator tightly bound to the enzyme. 4. Pyridoxal phosphate (PPL) may be a cofactor of ferrochelatase from both normal and porphyric rats. 5. The PPL would be involved in the binding site of Fe2+ or at least in the approaching of Fe2+ to the active site of the enzyme. 6. The differences found between normal and porphyric preparations could be attributed to conformational changes elicited by the HCB. PMID- 1864444 TI - Studies on the active centre of rat liver porphyrinogen carboxylase in vivo effect of hexachlorobenzene. AB - 1. Porphyrinogen carboxylase from the liver of normal and hexachlorobenzene porphyric rats was subjected to chemical modification using photo-oxidation with methylene blue, diethylpyrocarbonate, butane-2,3-dione, and phenylglyoxal. 2. All of these chemicals inactivated the enzyme from both sources. 3. Reversion of the diethylpyrocarbonate reaction with hydroxylamine as well as protection of the enzymes with uroporphyrinogen III indicated that histidine is involved at least in the first decarboxylation active site of the porphyrinogen carboxylyase, and perhaps in one or more sites where the removal of the other carboxyl groups take place. 4. Arginine seems not to be at the active site of the enzyme but at its environment since two diketones alter the enzyme activity, however the substrate did not protect the enzyme from the butane-2,3-dione modification. 5. Comparative studies between the enzyme from normal and porphyric animals suggest that the low enzyme activity from intoxicated animals could be due to alterations of its active centre environment produced by hexachlorobenzene treatment. This treatment seems to partially protect the active site of the porphyrinogen carboxylase from the modification reactions. PMID- 1864445 TI - Possible endogenous substrate proteins for cytosolic protein-tyrosine kinase from porcine spleen. AB - 1. Endogenous phosphate acceptor proteins by cytosolic protein-tyrosine kinase from porcine spleen (CPTK-40) were studied using subcellular fractions of porcine spleen and supernatant fraction of rat various tissues. 2. At least 13 phosphate acceptor proteins ranging from 94 to 26 kDa were observed in all but mitochondrial subcellular fractions. 3. Among the supernatant fraction of rat tissues, brain, testis and spleen contained many phosphate acceptor proteins. 4. The most heavily phosphorylated band of around 55 kDa which was commonly recognized among various tissues was confirmed as tubulin by the immunoreactivity with anti-tubulin antibody. 5. The results obtained in this paper indicate that CPTK-40 has the potential to catalyze the phosphorylation of numerous endogenous proteins including tubulin. PMID- 1864447 TI - Differential theophylline inhibition of alkaline phosphatase and 5'-nucleotidase of bovine milk fat globule membranes. AB - 1. The effects of theophylline (1,3-dimethylxanthine) on alkaline phosphatase and 5'-nucleotidase activities of bovine milk fat globule membranes (MFGM) were examined. 2. Theophylline inhibited MFGM alkaline phosphatase in a concentration dependent manner with 50% inhibition produced by 99 +/- 28 microM theophylline. 3. The 5'-nucleotidase activity was resistant to theophylline inhibition with 50% inhibition produced by 33.9 +/- 3.1 mM theophylline. 4. Theophylline was an uncompetitive inhibitor of MFGM alkaline phosphatase with a Ki of 126 +/- 15 microM. 5. The extent of theophylline inhibition of alkaline phosphatase activity was independent of the substrate utilized in the assay. 6. The effect of theophylline on bovine MFGM alkaline phosphatase was similar to theophylline effects on other mammalian alkaline phosphatases of liver/bone isoenzyme origin. PMID- 1864446 TI - Brain protein synthesis in rabbits following low level aluminium exposure. AB - 1. Infant rabbits received s.c.injections 3 times weekly of low doses of aluminium (A1) maltolate (0.5-1.5 mg Al/kg body wt) or aluminium lactate (8 mg Al/kg body wt) from 5 or 10 days of age to 14 or 22 days of age. 2. Brain was used to provide a cell-free protein synthesizing system and this system exhibited increased activity in preparations from Al-exposed infants. The mRNA fraction obtained from the brain polysomal RNA also was more active following Al exposure. 3. The synthesis of immunoprecipitable calmodulin was significantly elevated. PMID- 1864448 TI - Double-blind comparison of diclofenac potassium, ibuprofen and placebo in the treatment of ankle sprains. AB - In a double-blind, placebo-controlled comparative study in 60 patients with ankle sprains suffering from moderate to severe inflammation and tenderness, the efficacy and tolerability of 150 mg/day diclofenac potassium given for 7 days was superior to that of 1.2 g/day ibuprofen which was, in turn, superior to placebo. Efficacy was assessed by volumetric evaluation of inflammation of the injured ankle, tenderness on finger pressure, pain on movement and the severity of the joint injury. Patients used visual analogue scales to assess severity of pain at rest and on walking before and during treatment. Diclofenac potassium was significantly superior (P less than 0.02) to ibuprofen for all measures of efficacy (except severity of joint injury) and ibuprofen was consistently superior to placebo. No serious adverse effects were reported. In conclusion, diclofenac potassium has been demonstrated to be effective in the treatment of acute ankle sprains and it had a rapid onset of action and good tolerability. PMID- 1864449 TI - Double-blind, randomized crossover study of the percutaneous efficacy and tolerability of a topical indomethacin spray versus placebo in the treatment of tendinitis. AB - Percutaneous efficacy and tolerability of a new topical indomethacin spray compared with a corresponding placebo product were evaluated in a double-blind, randomized crossover study in 30 patients with tendinitis, i.e. 28 patients with peri-arthritis of the shoulder and two with epicondylitis. Each patient was treated with 4% indomethacin spray or the corresponding placebo product three to five times daily for a period of 14 days and then received the other treatment for the same period of time. The indomethacin spray demonstrated a clear efficacy compared with the placebo based on both objective criteria (elevation, abduction and internal rotation) and subjective criteria (spontaneous pain, pain on movement, pressure-induced pain, functional disturbances and sleep disturbances). Tolerability was excellent: only two patients had minor local cutaneous irritation with the indomethacin spray, which did not require interruption of treatment. Treatment with indomethacin spray appeared to be effective in 80% and well-tolerated in 93% of the patients studied. PMID- 1864450 TI - A double-blind study comparing oleum horwathiensis with placebo in the treatment of psoriasis. AB - The efficacy and tolerability of topically applied oleum horwathiensis were evaluated in a double-blind, placebo-controlled study of 42 patients with chronic stable psoriasis. Both groups of patients, 19 receiving oleum horwathiensis treatment and 23 receiving placebo treatment for 12 weeks, showed clinically significant effects of treatment. Oleum horwathiensis was more effective than placebo throughout the treatment period but the difference was not statistically significant at any time. No changes in laboratory values attributable to treatment were recorded. The symptoms of the oleum horwathiensis-treated group continued to be less severe than those of the placebo-treated group throughout the 12 weeks of follow-up. The follow-up period, however, occurred partly during the summer and since the clinical status of the patients may have been affected by climate the difference between the treatment groups was not analysed statistically. The tolerability and cosmetic acceptance of oleum horwathiensis were remarkably good, and good clinical efficacy in scalp lesions--which was not the subject of this study--was spontaneously reported by several patients. PMID- 1864451 TI - Imedeen for the treatment of degenerated skin in females. AB - Imedeen, a new compound for oral administration consisting of special protein fractions and some glucosaminoglycans extracted from marine fish, has been shown in previous pilot studies to have a repairing effect on sun-damaged skin. In an open study, 10 females with sun-damaged skin, aged 39-61 years, were treated with 0.5 g/day Imedeen for 90 days. At baseline and after 30, 60 and 90 days, the following parameters were clinically evaluated: wrinkles; mottles; dryness of skin; and brittleness of hair and nails. After 90 days' treatment all signs of sun-damage had improved and brittleness of hair and nails was normalized in all cases. These clinical observations were confirmed by changes in skin thickness and elasticity. In a second double-blind study, 30 females in the same age range and with similar signs of sun-damage were treated with 0.5 g/day Imedeen or placebo for 90 days. The results in the Imedeen-treated group corresponded to those in the first study whereas no response to treatment was observed in the placebo treatment group. PMID- 1864452 TI - Symptomatic cervical oesophageal ectopic (heterotopic) gastric mucosa treated with omeprazole. AB - A 60-year-old female patient with a 3-year history of nausea underwent oesophagogastroduodenoscopy. Red lesions were found in the cervical oesophagus: one of 2 cm and the other less than 1 cm. These lesions were biopsied and the larger lesion showed typical gastric mucosa. Following 40 mg/day omeprazole for 3 days all symptoms disappeared. Treatment was stopped after the patient remained symptom-free for 4 weeks. PMID- 1864453 TI - Diclofenac potassium for the treatment of traumatic joint distortions: an open multicentre study. AB - In an open multicentre study, 410 patients presenting with traumatic joint distortions, predominantly involving the ankle, were recruited for treatment with 50 mg diclofenac potassium given orally three times daily for 7 days. Due to various protocol violations, the number of patients eligible for efficacy and tolerability analysis were 340 and 344, respectively. Significant (P less than 0.001) improvement in mobility, swelling, local tenderness, functional impairment and pain intensity occurred after both 3 and 7 days of therapy. Overall efficacy was assessed as excellent/good in 83% and 87% of cases by the investigator and patient, respectively. Altogether, 66 (19.2%) patients complained of adverse effects, which were generally mild or moderate in severity. Gastrointestinal complaints accounted for around 70% of the reported side-effects. Premature discontinuation of therapy due to poor tolerability was necessary in 15 (4.4%) patients. In conclusion, diclofenac potassium was both effective and well tolerated when used for the short-term treatment of traumatic joint distortions. PMID- 1864454 TI - Influence of prostaglandin E1 on heavy proteinuria in slightly azotaemic diabetics. AB - Treatment of non-insulin-dependent diabetes mellitus patients with nephropathy of the nephrotic type using 40 micrograms prostaglandin E1 given intravenously twice daily for 4 weeks reduced the urinary protein concentration. Prostaglandin E1 also increased the total serum protein and serum albumin concentrations, and reduced creatinine clearance and plasma renin activity following frusemide loading. Treatment with the prostaglandin did not, however, significantly affect the blood urea nitrogen and the serum creatinine concentration. It is concluded that prostaglandin E1 has overt effects on diabetic nephropathy. PMID- 1864455 TI - Clinical and pharmacological review of the efficacy of orphenadrine and its combination with paracetamol in painful conditions. AB - Orphenadrine citrate, a monomethylated derivative of diphenhydramine, has been used as a muscle relaxant and as an analgesic both alone or as a constituent of combination products. Data on the efficacy of orphenadrine alone and in combination with paracetamol for painful conditions are evaluated in the present review. From the available animal data it is concluded that the antinociceptive effect of orphenadrine has been clearly demonstrated but data have also clearly indicated that it has muscle relaxant properties. Human placebo-controlled studies have shown some support for the view that orphenadrine on its own acts as a mild analgesic in painful conditions associated with muscle spasm. Although only a small number of well-controlled studies have been completed with the combination product of orphenadrine/paracetamol, each supports the view that the combination has superior efficacy over paracetamol alone. There is no doubt that the combination product is more efficacious than placebo. PMID- 1864456 TI - Is carnitine essential in children? AB - Carnitine has a fundamental biological role as a long-chain fatty acid carrier across the mitochondrial membrane and in ketone body formation. Although the body normally synthesizes carnitine, in certain circumstances such as total parenteral nutrition and haemodialysis a dietary supplement may be needed to maintain adequate levels. Several considerations suggest that carnitine is a truly essential nutrient in infancy and in other situations where the energy requirement is particularly high, e.g. pregnancy and breast feeding. There are, for example, congenital deficit syndromes due to enzymatic inadequacies. There is also the possible role of carnitine in serious metabolic disorders such as organic acidaemias and, above all, it has multiple physiological functions in major metabolic pathways which are essential for development and growth. PMID- 1864457 TI - Neurons are replenished in cultures of embryonic chick optic tectum after immunomagnetic depletion. AB - The effect of intercellular interactions on the determination and differentiation of early embryonic brain cells was tested by immunomagnetic cell separation techniques. Using the A2B5 monoclonal antibody, which in chick brain reacts with a neuron-specific surface ganglioside, we produced initially pure populations of optic tectum cells devoid of the antigen. A coincident depletion of neurofilament(+) cells (95%) and nonneuronal growth characteristics of the separated A2B5(-) cells indicated that the vast majority of neurons had been removed initially. Surprisingly, A2B5(+) cells rapidly appeared in separated A2B5(-) cell cultures. After 1 day, the percentage of A2B5(+) cells in separated cell cultures equalled those in unseparated cultures (approximately 50%). By a week in culture, A2B5(+) cells developed neuronal morphology and contained neurofilaments. A2B5(-) to (+) conversion was a regulated phenomenon in that removal of different proportions of the (+) cells resulted in different numbers of (-) to (+) conversions. New DNA synthesis was not required for the acquisition of cell surface A2B5 antigen or for differentiation of cells into definitive A2B5(+) neurons. Our results demonstrate that postmitotic embryonic brain contains cells which are capable of replacing depleted neurons in vitro. PMID- 1864458 TI - Spermatogenesis in Hydra oligactis. II. How temperature controls the reciprocity of sexual and asexual reproduction. AB - Hydra oligactis undergo two mutually exclusive modes of reproduction: at warm temperatures (18-22 degrees C) animals reproduce asexually by budding, while at cold temperatures (10-12 degrees C) gamete differentiation occurs. Using a monoclonal antibody which is specific for cells of the sperm lineage, it was discovered that under conditions where sperm differentiation does not occur (18 22 degrees C), cells continually enter the sperm pathway but progression down the pathway is prematurely halted, effectively blocking the production of sperm. To elucidate the mechanism by which completion of sperm differentiation is controlled, the cell cycle times of interstitial cells entering the sperm pathway at both the restrictive (18 degrees C) and permissive (10 degrees C) temperatures were examined. It was envisaged that at the restrictive temperature the cell cycle times of committed cells would lengthen as they proceeded down the pathway, leading to dilution and eventual loss of cells at later stages of sperm differentiation. This did not occur. Although cells of the sperm lineage were found overall to divide more slowly at 18 degrees C than at 10 degrees C, at both temperatures the cell cycle times shortened as cells proceeded further down the pathway, making a dilution mechanism untenable. The effect of high temperature on the survival of cells was then tested by subjecting animals to a heat shock. Within 12 hr of the increase in temperature, the total number of sperm lineage interstitial cells dropped 10-fold while the total numbers of epithelial and somatic interstitial cells remained virtually unchanged. A distinct consequence of this cell loss was the disappearance of cells furthest down the sperm pathway. It is proposed that as cells move down the sperm pathway, they become increasingly sensitive to high temperature which adversely affects their survival; the higher the temperature, the earlier in the pathway cells die. The lethal effect is abolished by lowering the temperature, allowing sperm differentiation to continue to completion. The possible adaptive advantages of temperature controlling gametogenesis are discussed. PMID- 1864459 TI - Immunofluorescence localization of an adducin-like protein in the chromosomes of mouse oocytes. AB - The mouse oocyte expresses a polypeptide of Mr 120,000 that cross-reacts with an antibody to the brain membrane skeletal protein adducin. Immunofluorescence localization showed a bright chromosomal staining reaction in metaphase I and metaphase II oocytes. Following in vitro fertilization the maternal chromosomes lost their immunoreactivity during pronuclear development. The fertilizing sperm chromatin and male pronucleus did not show any detectable staining reaction. Bright chromosomal fluorescence was again observed in the first mitotic metaphase when both maternal and paternal chromosomes gave a positive staining reaction. In contrast to the immunoreactivity of the maternal meiotic chromosomes, the meiotic chromosomes of male germ line cells failed to exhibit any detectable staining reaction and this difference was confirmed by immunolabeling of oocyte and spermatocyte karyotypes. Mitotic chromosomes in preimplantation embryos, fetal liver, adult intestinal epithelium, and MDCK cells also failed to show any detectable labeling reaction. The results suggest that expression of the immunoreactive chromosomal adducin may be a unique feature of oogenesis. PMID- 1864460 TI - Cytokines modulate preimplantation development and pregnancy. AB - Using two different models of pregnancy failure in mice, we show in this communication that preimplantation embryonic development can be controlled, in vivo, with cytokines. In one model, described by us previously, CSF-1 is shown to block gestations in plugged females due to its induction of defective early development. Pregnancies and preimplantation development are shown here to be restored to normal by TNF alpha or GM-CSF but not by TGF beta 1. In the second model, we reveal that CBA/J females plugged by various male strains produce spontaneously an extremely high proportion of abnormal precompaction embryos. Normal morulae and blastocysts, able to further develop and implant in vitro, are shown here to be induced by TNF alpha and to a lesser extent by GM-CSF and IL-1 alpha. These results suggest strongly that cytokines are potent modulators of early development. They may provide new and interesting insights into early events of mammalian embryonic development. PMID- 1864461 TI - Simultaneous maturation of transverse tubules and sarcoplasmic reticulum during muscle differentiation in the mouse. AB - The development and maturation of transverse (T) tubules and sarcoplasmic reticulum (SR) have been studied in pre- and postnatal mouse muscle, using selective "staining" of these membrane systems. As previously reported in the literature, orderly transverse orientation of the T tubules occurs late in development and early T-SR junctions (triads and dyads) are located at random along the T tubules in a predominantly longitudinal orientation. We find that initial appearance of transverse tubules occurs fairly abruptly, and that all early T tubules have a longitudinal orientation. Transverse orientation of the T tubule network, location of triads at the A-I junction, and development of differentiated regions of the SR are coordinated events which occur gradually over a period of about 3 weeks for leg muscle.s The timing of triad development coincides with that reported for the increase in slow calcium current and dihydropyridine binding. Differences in T tubule patterns between muscle fibers of EDL and soleus are apparent only at relatively late stages. PMID- 1864462 TI - Intrinsic electric fields promote epithelization of wounds in the newt, Notophthalmus viridescens. AB - The lateral electric fields (LFs) in the vicinity of small wounds made in hindlimb digit tip skin of Notophthalmus viridescens have been measured and manipulated. Healing of these wounds was assessed by crystal violet staining and by histology. Paired experiments were conducted on the animals: the healing of one digit's wound was compared with healing of the contralateral digit's wound whose LF was changed from that of its contralateral wound. When currents were passed through the animal (into one wound and out of the contralateral wound) so that the LF of one wound was zero while the contralateral wound had an enhanced LF, the wounds with the enhanced LF healed more rapidly than the wounds with the zero LF. When digits on one side were treated with 30 microM benzamil in an artificial pond water so that their wound LFs were reduced to approximately zero, and the contralateral wounds were kept in artificial pond water without benzamil so that they had normal wound LFs, there was significantly less epithelization of the benzamil-treated wounds than of the control wounds. This effect on wound healing was reversed by adding currents that restored the normal wound LFs, but not by adding currents that reversed the wound LFs to the opposite polarity. When currents were added to reverse the wound LFs on one side of the animal, leaving the contralateral wounds free of added currents, the wounds with the reversed LFs healed more poorly than the contralateral wounds with normal LFs. These results are consistent with the hypothesis that the intrinsic LFs in the vicinity of wounds promote epithelization of these wounds. PMID- 1864463 TI - The calcium content of cortical granules and the loss of calcium from sea urchin eggs at fertilization. AB - In many species, fertilization triggers a wave of cortical granule exocytosis in the egg that is the consequence of an increase in intracellular free calcium concentration. We have measured the total calcium content of cortical granules from two species of sea urchins by quantitative X-ray microanalysis and spectrometric measurements. Our results show that cortical granules: (1) contain a high concentration of total calcium (around 30 and 95 mM for Paracentrotus lividus and Arbacia lixula, respectively), (2) represent a major cortical storage site of calcium in the egg (5 and 11% of total egg calcium for P. lividus and A. lixula, respectively), and (3) exchange part of their accumulated calcium by an ATP dependent mechanism. In addition we have confirmed that at fertilization, sea urchin eggs lose a sizeable amount of their calcium (7% for P. lividus and 15% for A. lixula). The kinetics and magnitude of the loss suggest that some of this calcium could be provided by cortical granules during exocytosis. PMID- 1864464 TI - Mutations within the Ddc promoter alter its neuron-specific pattern of expression. AB - The Drosophila dopa decarboxylase gene (Ddc) is expressed in a reproducible set of approximately 150 neurons, and in a subset of the glia of the third instar larva's central nervous system (CNS). Expression in this pattern requires a cell type-specific neuronal enhancer/glial repressor region located 1000 bp from the transcriptional start site, and specific sequences within the promoter. We have used mutagenesis in vitro and P-element-mediated transformation to examine the role of the promoter, particularly its major CNS activator sequence (element I), in the generation of the wildtype expression pattern. Immunohistological analysis of these transgenic strains demonstrates that particular deletion mutations shift the site of transgene expression to a set of neurons which do not express Ddc at detectable levels in wild-type larvae. Transgene expression in these strains may be driven by a previously undetected activator sequence. Our data also suggest that glial expression may be driven by the same activator sequences that drive expression in the hypoderm. PMID- 1864465 TI - The SGP-2 gene is developmentally regulated in the mouse kidney and abnormally expressed in collecting duct cysts in polycystic kidney disease. AB - Sulfated glycoprotein-2 (SGP-2) is a secreted, dimeric, glycosylated protein synthesized by a number of different epithelial cell types. Although its function is not yet understood, SGP-2 has been hypothesized to be involved in such diverse processes as the promotion of cell-cell interactions, spermatogenesis, modulation of the complement system, and programmed cell death. We have now found that the SGP-2 gene is developmentally regulated in the mouse kidney. SGP-2 gene expression is first detected in the condensing nephrogenic mesenchyme and is subsequently down-regulated during the maturation of the glomerular epithelia, proximal tubules, and collecting ducts. SGP-2 continues to be expressed in the mature kidney in distal tubules and in the urothelial lining of the calyx and papilla. We have also examined the expression of the SGP-2 gene in polycystic kidneys of the C57BL/6J-cpk mouse, a model of autosomal recessive polycystic kidney disease in which there is development of epithelial-lined cysts arising primarily from the collecting duct system. Abnormally high levels of SGP-2 mRNA were found in the cyst wall epithelium of polycystic kidneys. The expression of the SGP-2 gene in normal development suggests that it plays a role in differentiating epithelial structures; and the abnormally high levels of SGP-2 gene expression in polycystic kidneys suggests that the cells lining cysts are not fully differentiated. It is possible, therefore, that polycystic kidney disease is caused by a defective developmental process in which there is a delay in terminal differentiation. PMID- 1864466 TI - Pharmacology of the serotonin-induced meiosis reinitiation in Spisula solidissima oocytes. AB - Germinal vesicle breakdown (GVBD) is the first visible response of the oocyte of Spisula solidissima to the neurohormone serotonin. Pharmacological characterization of this response was performed by using 24 serotonin-related compounds. Dose-response curves were assessed by quantification of GVBD. Rank orders of potency obtained were among agonists: serotonin greater than 8-hydroxy 2-(di-N-propylamino)tetralin hydrobromide greater than 2-methyl-serotonin greater than 1-(3-trifluoromethylphenyl)piperazine; among antagonists; ritanserin ritanserin greater than ICS205930 greater than mianserin = ketanserin = propranolol greater than metoclopramide = yohimbine greater than spiperone. Various other monoaminergic compounds tested were inefficient, demonstrating the specificity of the oocyte response to serotonin. Transduction mechanisms underlying this response were then investigated. Ca2+ appeared to be involved since serotonin induced an increase in the uptake of 45Ca2+ and since it was inefficient in calcium-free sea water. The absence of synergy between serotonin and KCl suggested that both compounds use a common transduction pathway. Exposure of the oocyte to the protein kinase C activator TPA inhibited serotonin-dependent maturation. Our data thus point to an original, previously uncharacterized pharmacological profile and transduction mechanism by which serotonin induces oocyte meiosis reinitiation in Spisula solidissima. PMID- 1864467 TI - Overexpression of uvomorulin in a compaction-negative F9 mutant cell line. AB - The mutant F9 cell line F9att-5.51 synthesizes reduced amounts of uvomorulin (UM) protein and we hypothesized earlier (Adamson, Baribault, and Kemler, Dev. Biol. (1990), 138, 338) that this may account for its inability to compact into tightly aggregated balls of cells. Subsequently, when 5.51 cells are treated with retinoic acid to stimulate their differentiation, they are unable to form embryoid bodies as do wild-type cells which form an outer epithelial layer of visceral endoderm cells. We have now examined the possibility that the UM protein made in the mutant line is defective, but find that it is normal in structure and stability. The gene coding for UM appears to be normal as does the mRNA which is synthesized at a normal rate but is severely reduced in steady-state measurements of mutant cells. A rescue experiment was performed by increasing levels of UM in mutant cells by means of transfection with a UM expression vector. The resulting cells expressed abundant UM mRNA and protein but were still unable to form compacted aggregates and did not differentiate into embryoid bodies. Interestingly, the stability of endogenous UM mRNA was improved in the presence of exogenous UM; therefore, a positive feedback mechanism contributes to low mRNA levels in mutant cells. The accumulated data suggest that UM in 5.51 cells is unable to mount a compaction activity because a distal connecting link in the multicomponent process initiated by UM is missing or or aberrant. The missing component is likely to connect UM to actin and the cytoskeleton of the cell. PMID- 1864468 TI - Peptides from sperm acrosomal protein that initiate egg development. AB - How sperm initiate egg development is being investigated with gametes of the marine worm Urechis. Sperm acrosomal protein, previously shown to activate eggs (Gould et al., 1986, Dev. Biol. 117, 306-318; Gould and Stephano, 1987, Science 235, 1654-1656), was enzymatically cleaved into soluble peptide fragments. When this mixture was added to eggs they activated, and parthenogenetic cleavage often occurred. An active peptide (P23) was purified from the mixture and its sequence was determined to be Val-Ala-Lys-Lys-Pro-Lys. Synthetic peptide had the same biological activity. P23 induced eggs to undergo the complete sequence of changes that normally follows fertilization, including the fertilization potential, completion of meiosis, and DNA replication. When a sperm centrosome was introduced into eggs by prefertilization without activation, and the eggs were subsequently activated by P23, they developed normally to trochophore larvae (the contribution of another sperm component is not ruled out by this experiment). P23 covalently coupled to bovine serum albumin also activated eggs, showing that it acted on the external surface of the egg. The peptide did not activate sea urchin eggs, but did cause oyster eggs to undergo germinal vesicle breakdown. PMID- 1864469 TI - cut-1 a Caenorhabditis elegans gene coding for a dauer-specific noncollagenous component of the cuticle. AB - We have molecularly identified a new gene of Caenorhabditis elegans that codes for a component of the cuticle. The gene has been physically mapped on LGII near the locus sqt-1. The structure and the sequence of the gene have been determined and antisera have been raised against parts of the protein produced as fusions in Escherichia coli. By transcription analysis, and by the use of specific antisera, we have determined that this gene is expressed specifically during dauer larva formation. In extracts of worms completing the dauer transformation the product of this gene migrates in sodium dodecyl sulfate acrylamide gels with an apparent molecular mass of 40 kDa. By immunofluorescence we have determined that it is a component of the cuticles of dauer larvae. It forms a ribbon approximately 2 microns wide running along the lateral lines underneath the alae. Once it is assembled in the cuticle the protein becomes insoluble even in the presence of strong detergents and reducing agents in a manner that is similar to that described for the noncollagenous, insoluble residue of nematode cuticles called cuticlins; therefore, we have named the gene cut-1 for cuticlin 1. cut-1 represents the first gene for a noncollagenous component of C. elegans cuticle that has been characterized molecularly. PMID- 1864470 TI - Cell movements during the initial phase of gastrulation in the sea urchin embryo. AB - The morphogenetic processes responsible for the initial phase of gastrulation in sea urchin embryos are not known. Here we report observations of the size and position of clones of cells derived from horseradish peroxidase (HRP)-injected mesomeres and macromeres. The displacement of these clones during the initial phase of gastrulation suggests that involution is a mechanism involved in primary invagination. Experiments with embryos marked with vital dyes indicate that movements occur only during a brief phase coincident with the invagination of the vegetal plate. Counts of cells derived from HRP-injected mesomeres and macromeres suggest it unlikely that localized growth in the vegetal plate is involved in gastrulation. An analysis of changes in cell shape during the initial phase of gastrulation indicates that there is a stage-dependent shift from cells being columnar to having their apices skewed toward the vegetal plate and an increase in the proportion of cells having basal processes during gastrulation. When embryos are grown in the presence of monoclonal antibodies to the apical lamina or monovalent fragments of these antibodies, the initial phase of gastrulation is delayed and they form partial exogastrulae. Analysis of embryos marked with HRP indicate that the antibody treatments interfere with the cellular movements observed in untreated embryos. We conclude that directed movements of cells within the blastoderm, probably employing tractoring on components of the hyaline layer, cause the buckling of the vegetal plate and displacement of presumptive endoderm cells seen during the initial phase of gastrulation. PMID- 1864471 TI - Chronic exposure to an activator of protein kinase C mimics early effects of NGF in chromaffin cells. AB - Adrenal chromaffin cells respond to nerve growth factor (NGF) in vitro by expressing neuronal characteristics and, over a period of 2 to 4 weeks, transdifferentiating into postmitotic sympathetic neurons. Phorbol myristate acetate (PMA) is a potent activator of protein kinase C (PKC); chronic exposure to PMA mimics the initial actions of NGF by promoting the outgrowth of neurites and increasing the incorporation of [3H] thymidine in primary cultures of adrenal chromaffin cells from young rats. PMA and NGF affect the same populations of cells and even individual neurites. These effects are specific for active phorbol ester and do not result from the release of NGF or FGF in the cultures. As in the case of NGF, the effects are inhibited by glucocorticoids. The PKC inhibitor staurosporine inhibits the effects of PMA, as well as those of NGF, in a dose dependent manner. These results suggest that a modulation in activity of PKC is important in the neuritogenic and proliferative effects of NGF, at least for an initial period of approximately 1 week. PMID- 1864472 TI - Walking. PMID- 1864473 TI - Modifications to the traditional description of neurosegmental innervation in myelomeningocele. AB - The consistency between patterns of lower-limb muscle strengths in children with myelomeningocele and Sharrard's classic description of segmental innervation was examined in 291 patients. Although it has been assumed that medial hamstring innervation was from a similar neurosegmental level as gluteus medius, and gluteus maximus was from a similar level as gastrocnemius-soleus, the authors found that medial hamstring strength more frequently correlated with iliopsoas and quadriceps, and glutei with anterior tibialis. It is proposed that children with myelomeningocele be grouped according to specific muscle strength rather than by neurosegmental level. PMID- 1864474 TI - Ambulatory outcome of children with myelomeningocele: effect of lower-extremity muscle strength. AB - The relationship between patterns of strength and mobility was studied in 291 children with myelomeningocele, graded as community ambulators, partial (household) ambulators and nonambulators. Iliopsoas strength was found to be the best predictor of ambulation, with the quadriceps, anterior tibialis and glutei also contributing significantly. Grade 0 to 3 iliopsoas strength was always associated with partial or complete reliance on a wheelchair. No patient with grade 4 to 5 iliopsoas and quadriceps function relied completely on wheelchairs and the majority were community ambulators. Grade 4 to 5 gluteal and anterior tibialis function was associated with community ambulation, without aids or braces. Deterioration in mobility was most common in those with strong iliopsoas/quadriceps and grade 0 to 3 gluteus medius, and was not age-related. PMID- 1864475 TI - Treatment versus non-treatment of hip dislocations in ambulatory patients with myelomeningocele. AB - Thirty myelomeningocele patients with untreated hip dislocations who had functional quadriceps and good ambulatory capability were evaluated for hip pain, hip motion and sitting ability: they had no pain, good to excellent hip motion and no difficulty in sitting. Three were wheelchair-bound. Nine had a limb-length inequality requiring a shoe lift. They were compared with a similar series of 11 patients who underwent open reduction of a dislocated hip with a two-year follow up. Two patients in this group had improved and three had worse sitting balance. Serious perioperative complications occurred in six patients. The authors conclude that surgical reduction of paralytic hip dislocations in ambulatory myelomeningocele patients is costly and offers little obvious benefit. PMID- 1864476 TI - Neuropsychiatric assessment of children with autism: a population-based study. AB - Thirty-five children with autistic disorder and 17 with autistic-like conditions underwent an exhaustive neurobiological evaluation, and the findings were contrasted with those obtained from various comparison groups. Almost 90 per cent of the children with autistic disorder and autistic-like conditions had major indications of brain damage or dysfunction. Some of those who did not show such abnormalities had a first-degree relative with Asperger syndrome. The rate of abnormality was similar to that of severely mentally retarded children, but in excess of that of normal children. Within the autism group, abnormality rate did not correlate with degree of mental retardation. It is concluded that autism has multiple biological aetiologies and that autistic symptoms in a child should always prompt a thorough medical/neurobiological evaluation. PMID- 1864477 TI - Hemiplegic cerebral palsy: correlation between CT morphology and clinical findings. AB - Morphological findings on CT were compared with clinical features of 111 children with hemiplegic cerebral palsy. Periventricular atrophy, interpreted as periventricular leukomalacia, was the most prevalent CT finding, although this type of lesion did not indicate severity of neurological impairment. Maldevelopments were associated with arm-dominated hemiplegia and with a wider range of clinical impairments than previously described. Cortical/subcortical atrophy, less common than presumed, indicated arm-dominated hemiplegia and was associated with more severe impairment than were other CT findings. A normal CT scan indicated leg-dominated hemiplegia and mild impairment. The morphological information obtained by CT was found to be useful for predicting clinical outcome, and was considered an important adjunct to clinical history and findings in these children. PMID- 1864478 TI - Cognitive impairment in new cases of epilepsy randomly assigned to carbamazepine, phenytoin and sodium valproate. AB - Sixty-four new cases of childhood epilepsy were randomly assigned to either carbamazepine, phenytoin or sodium valproate, and were assessed with cognitive tests before medication and three subsequent times over a year. Carbamazepine in moderate dosage adversely affected memory, but sodium valproate and phenytoin did not. PMID- 1864479 TI - Central nervous system involvement of children with HIV infection. AB - The neurological findings in 41 HIV-seropositive children are described. 23 children were symptomatic, eight seropositive but without symptoms and 10 seropositive children less than 15 months of age had no other evidence of immunodeficiency. Acquired microcephaly, developmental regression and progressive motor deterioration indicated HIV encephalopathy, as did developmental delay, mental retardation, cerebellar symptoms and behavioural changes. Three children with progressive encephalopathy improved after treatment with azidothymidine (AZT). In eight children treated with prophylactic intravenous immunoglobulin therapy (IVIG) and seven treated with both IVIG and AZT, no mental deterioration has been observed since the beginning of therapy. One child with advanced encephalopathy and severe pyramidal tract involvement did not improve. PMID- 1864480 TI - Cutaneomuscular reflexes recorded from the first dorsal interosseous muscle of children with cerebral palsy. AB - Cutaneomuscular reflexes were recorded from the first dorsal interosseous muscles of 21 children with spastic cerebral palsy. The reflex responses in children with cerebral palsy were consistent with dysfunction of the pyramidal system, but differed from those seen in adults with central nervous lesions. This provides further evidence that the effect of a central nervous lesion on the reflex control of movement is dependent on whether it occurs in early or adult life. PMID- 1864481 TI - Genomic imprinting. PMID- 1864482 TI - Recovery by mouse embryos following teratogenic exposure to ketosis. AB - Previous studies have shown that the ketone body D,L,-beta-hydroxybutyrate was teratogenic to mouse embryos exposed in culture during the period of neurulation. Inhibition of closure of the cranial and caudal neuropores was the most frequently occurring defect and these abnormalities were thought to be the forerunner of anencephaly and spina bifida, respectively. However, additional studies demonstrated that embryos could recover morphologically from these effects if the ketone body was removed from the culture medium and if the recovery period was of sufficient duration. In an attempt to define further the phenomenon responsible for this recovery and to determine the extent of the recovery process, the present study examining the cross-sectional area, cell number, and mitotic index of cranial neuroepithelial cells was conducted in mouse embryos cultured from the early somite stage under one of the following conditions: 1) control medium for 60 h; 2) medium containing 32 mmol/l D,L,-beta hydroxybutyrate for 24 h followed by culture in control medium for an additional 36 h (recovery group); 3) medium containing 32 mmol/l D,L,-beta-hydroxybutyrate for 60 h (continuously exposed group). The results indicate that although neural tube closure occurred in the recovery group, complete recovery was limited to the ventral regions of the forebrain and that the remainder of the prosencephalon as well as the rhombencephalon failed to undergo complete catch-up growth. Thus, cell numbers in these areas were approximately 70% of control values. Therefore, while the gross anatomical disturbances produced by the ketone body may be compensated for, histological alterations in the affected tissues remain. Ultimately, these data suggest that neurological deficits may be an outcome of ketone body exposure during the early stages of embryogenesis. PMID- 1864483 TI - Insulin treatment prevents diabetes mellitus but not thyroiditis in RT6-depleted diabetes resistant BB/Wor rats. AB - Prophylactic insulin administration is known to prevent hyperglycaemia in diabetes prone BB rats and non-obese diabetic mice. This study investigated the effect of insulin treatment on the development of overt diabetes, clinically inapparent anti-islet autoreactivity, and thyroiditis in RT6-depleted diabetes resistant BB rats. Fewer than 1% of these animals develop spontaneous diabetes, but if depleted of RT6- T cells greater than 50% become hyperglycaemic. We treated 30-day-old diabetes resistant rats with anti-RT6.1 monoclonal antibody, exogenous insulin, or both. Up to 60 days of age, 16 of 20 rats given antibody alone became diabetic, compared with 1 of 20 also treated with antibody plus insulin. Up to 110 days of age, only 1 of 10 rats treated with both insulin and antibody between 30 and 60 days became diabetic. Histologic study of non-diabetic insulin plus anti-RT6 antibody treated rats revealed insulitis in 3 of 9 at 60 days old, and insulitis in 3 of 8 and thyroiditis in 6 of 7 at 110 days of age. Non-diabetic animals were also found to harbour autoreactive spleen cells that adoptively transferred diabetes. Splenocytes from 60 or 110-day-old non-diabetic donors that had been treated with insulin and antibody between 30 and 60 days of age induced diabetes in 7 of 13 and 6 of 8 adoptive recipients respectively. We conclude that insulin treatment prevents clinical diabetes in the RT6-depleted diabetes resistant BB rat, but this treatment does not prevent the development of autoreactive cell populations that cause thyroiditis and adoptively transfer diabetes. PMID- 1864484 TI - Anionic sites in diabetic basement membranes and their possible role in diffusion barrier abnormalities in the BB-rat. AB - Basement membrane anionic sites, thought to be responsible for charge selective permeability barriers, were investigated in retinal, endoneurial, and muscle capillary basement membranes and in Bruch's membrane of diabetic, and age- and sex-matched non-diabetic BB-rats using an ultrastructural quantitative histochemical technique. Six months of diabetes was associated with significant basement membrane thickening which was linearly related to a decrease in anionic site density suggesting a relative loss of proteoglycans. Calculation of anionic sites per unit length of basement membrane, reflecting their absolute number, revealed a significant loss in basement membrane, constituting part of normal blood-tissue barrier systems such as retinal and endoneurial capillary basement membranes, and the basement membrane of the retinal pigment epithelium. The absolute number of anionic sites in normally permeable microvessels, such as those of muscle and choriocapillaries, was unaltered by diabetes. We conclude that this specific loss of anionic sites in basement membranes of tissues affected by chronic diabetic complications may in part be responsible for permeability abnormalities seen in these tissues. PMID- 1864485 TI - Insulin prevents adoptive cell transfer of diabetes in the autoimmune non-obese diabetic mouse. AB - Early intensive insulin treatment is thought to improve subsequent Beta-cell function in Type 1 (insulin-dependent) diabetic patients. Prophylactic insulin administration also reduced diabetes incidence in diabetes-prone animals. To study the mechanisms by which these effects occur, we tested the ability of insulin therapy in the model of non-obese-diabetic mice, to prevent the penetration of committed T cells into the islets and subsequent Beta-cell destruction. Sublethally irradiated non-obese-diabetic males of 8 weeks of age were adoptively transferred with splenocytes from diabetic donors and treated with the maximum tolerable dosage of fast-acting insulin (0.5 U, twice daily) until 30 days after cell transfer. Diabetes incidence was compared to control animals injected with the same concentration of insulin diluent. After one month of treatment, the cumulative diabetes frequency was significantly less within the insulin-treated group (4 of 15, 26.6%) than in the control group (15 of 18, 83.3%; p less than 0.01). Pancreatic histological analysis of insulin-treated animals revealed a lower severity of insulitis and Beta-cell necrosis and a higher percentage of normal islets (46.6 +/- 10% vs 2.3 +/- 2%, p less than 0.01), including five (33%) mice with no lesions. Immunoperoxydase staining of pancreatic sections indicated similar insulin and ganglioside staining of Beta cells from insulin-treated mice and control animals. Insulin-treated mice had comparable pancreatic insulin content to normal mice. Flow cytometry analysis of spleen cell populations indicated that insulin increased the number of Thy1,2+ and Lyt-2+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864486 TI - Relationship between serum pseudocholinesterase and triglycerides in experimentally induced diabetes mellitus in rats. AB - This study was designed to understand the reasons for the increase in serum pseudocholinesterase activity in diabetes mellitus. Streptozotocin-induced diabetic rats were used for the study. Serum pseudocholinesterase activity increased with the induction of diabetes (381.5 units/l +/- 11.8) compared to the non-diabetic rats (243.1 units/l +/- 7.2). Serum triglycerides, total low density lipoprotein and glycerol also increased concurrently with the development of diabetes. Insulin treatment of the diabetic rats normalized serum glucose concomitant with the reduction of pseudocholinesterase activity, triglycerides, total low density lipoprotein and glycerol. Heparin injection appeared to activate lipoprotein lipase in the diabetic rats by showing a marked fall in serum triglyceride and total low density lipoprotein levels but not in pseudocholinesterase activity. Administration of tetraisopropylpyrophosphoramide a specific pseudocholinesterase inhibitor, inhibited serum and adipose tissue pseudocholinesterase activity by greater than 80% and liver greater than 50%. Concurrent with the inhibition of pseudocholinesterase activity serum triglyceride, low density lipoprotein and glycerol decreased significantly. In normal rats treatment with tetraisopropylpyrophosphoramide also reduced serum lipoproteins markedly, while glycerol only showed a marginal decrease. Glycerol was used as a marker of adipose tissue lipolysis and total low density lipoprotein which is defined as lipoproteins of density less than 1.063 (LDL + VLDL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864487 TI - Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro. AB - This study addresses the possibility that the teratogenic effects of a diabetic pregnancy are associated with increased embryonic activities of free oxygen radicals. Rat embryos were cultured in 50 mmol/l glucose for 48 h and subsequently showed pronounced growth retardation and severe malformations. The enzyme inducer citiolone and the free oxygen radical scavenging enzymes superoxide dismutase, catalase and glutathione peroxidase protected against the disturbed growth and development of the embryos at 50 mmol/l glucose when added to the culture media. Enzymatic measurements indicated that citiolone induced an increased activity of superoxide dismutase in the embryonic tissues and that the added enzymes were taken up by both the yolk sac and the embryo proper. The protection against embryonic maldevelopment was thus conferred by agents that increased the free oxygen radical scavenging capacity of the embryonic tissues. The results suggest that a high glucose concentration in vitro causes embryonic dysmorphogenesis by generation of free oxygen radicals. An enhanced production of such radicals in embryonic tissues may be directly related to the increased risk of congenital malformations in diabetic pregnancy. PMID- 1864488 TI - Cumulative cognitive impairment following recurrent severe hypoglycaemia in adult patients with insulin-treated diabetes mellitus. AB - To examine the hypothesis that episodes of severe hypoglycaemia may cause cumulative cognitive impairment. 100 Type 1 (insulin-dependent) diabetic patients were examined. Their age range was 25-52 years, and the onset of diabetes had occurred after the age of 19 years. Patients with evidence of organic brain disease, including cerebrovascular disease, were excluded. A questionnaire was used to assess the number, frequency and severity of hypoglycaemic episodes experienced during treatment with insulin and the accuracy of this retrospective information was verified from general practice and hospital case-notes. A detailed neuropsychological assessment was undertaken, including tests of pre morbid and present IQ (Wechsler-Revised), memory and information-processing speed. Significant correlations were observed between the frequency of severe hypoglycaemia and the magnitude of intellectual decline, Performance IQ, inspection time and reaction time (patients with the more frequent hypoglycaemia had poorer performance). Two sub-groups of patients were identified on the basis of their experience of severe hypoglycaemia, and were balanced for pre-morbid IQ, age and duration of diabetes. One sub-group (n = 23) had never experienced severe hypoglycaemia (Group A), whilst the other sub-group (n = 24) had suffered at least five episodes of severe hypoglycaemia (Group B). Group B had greater intellectual impairment than Group A, and Group B also had a significantly slower mean reaction time and higher reaction time variance when compared with Group A. PMID- 1864489 TI - Normalization of hepatic glucose regulation despite systemic insulin delivery. Studies in patients with pancreatic transplantation for type 1 (insulin dependent) diabetes mellitus. AB - With current surgical techniques for pancreatic transplantation, the graft is anastomosed to the iliac vessels, resulting in delivery of insulin to the systemic circulation rather than to the portal vein as in healthy man. The possible influence of the altered route of insulin delivery on the regulation of splanchnic glucose metabolism was studied in four patients with Type 1 (insulin dependent) diabetes mellitus at 6-19 months after combined pancreatic and kidney transplantation. Four non-diabetic, age-matched renal transplant recipients and two groups of age-matched healthy subjects served as controls. The studies were carried out in the basal state and during two rates of intravenous glucose infusion (2 and 4 mg.kg-1.min-1). Fasting arterial glucose and splanchnic glucose output was similar in all groups. Basal hyperinsulinaemia was present in pancreatic graft recipients compared to healthy subjects. During low rate intravenous glucose infusion splanchnic glucose output decreased to a similar extent in all groups. With the higher glucose infusion rate (4 mg.kg-1.min-1) a net glucose uptake was observed which was similar in all three groups. Peripheral glucose uptake was unchanged at the lower glucose infusion rate but increased by 45-55% at the higher rate. It is concluded that despite systemic insulin delivery from a heterotopic pancreatic graft, hepatic glucose metabolism appears normal both in the post-absorptive state and in response to glucose-stimulated endogenous insulin secretion. Portal insulin delivery is thus not necessary for normal hepatic glucose metabolism in the Type 1 diabetic patient. PMID- 1864490 TI - Shared genetic susceptibility of type 1 (insulin-dependent) and type 2 (non insulin-dependent) diabetes mellitus: contributions of HLA and haptoglobin. AB - Epidemiologic data suggest that having a parent with Type 2 (non-insulin dependent) diabetes mellitus increases the risk for Type 1 (insulin-dependent) diabetes in siblings of a Type 1 diabetes proband. This increase in risk is consistent with a shared genetic susceptibility between Type 1 diabetes and Type 2 diabetes. We contrast genetic risk factors in three sets of families, consisting of (1) a single Type 1 diabetic child (proband) and non-diabetic parents, (2) multiple Type 1 diabetic siblings and non-diabetic parents, and (3) at least one Type 1 diabetic child and at least one Type 2 diabetic parent. Previous studies have demonstrated that HLA region genes, which elevate the risk in Type 1 diabetes, have no significant effect with respect to the risk for developing Type 2 diabetes. An earlier report cited a contribution by the haptoglobin locus to genetic susceptibility for Type 2 diabetes. We provide evidence that a high risk HLA antigen (HLA-DR3) is decreased to a greater extent in Type 1 patients with a Type 2 parent than in Type 1 patients in which the parents are not diabetic. The role of HLA-DR4 is maintained in these families, with an unexpectedly significant increased rate of transmission of the HLA-DR4 allele from Type 2 parent to Type 1 offspring. The role of haptoglobin in these families does not appear to be important, either with respect to association with diabetes or with respect to linkage with a secondary susceptibility locus. These results indicate that families with a Type 2 parent and Type 1 child, heavily determined by HLA-DR4 linked factors, may represent a homogeneous subset of diabetes susceptibility. PMID- 1864491 TI - Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study, 15-year follow-up. AB - The Paris Prospective Study is a long-term, large-scale study of the factors predicting coronary heart disease. The first follow-up examination included, for subjects not known as having diabetes mellitus, a 75 g oral glucose tolerance test with measurement of plasma insulin and glucose levels, fasting and 2 h post load. Between 1968 and 1973, 6903 men aged 43-54 years were thus examined. Causes of death were ascertained within this group after 15 years of mean follow-up. The baseline variables were tested as predictors of death from coronary heart disease by a Cox regression analysis. Significant independent predictors of coronary heart disease death were: systolic blood pressure, number of cigarettes per day, plasma cholesterol level, and 2 h post-load plasma insulin level when entered as a categorical variable (below or above 452 pmol/l. i.e. the lower limit of the fifth quintile of the distribution). This dichotomization was performed to account for the non-linear univariate distribution of deaths with increasing post load insulin values. Fasting plasma insulin level was not an independent predictor of death by coronary heart disease over this long-term follow-up. Levels of blood glucose were not significant independent predictors of death by coronary heart disease when plasma insulin levels were included in the model. The same applied to abnormalities of glucose tolerance when the 125 men with known non-insulin-treated diabetes at baseline were added to the group. Under the assumption that hyperinsulinaemia is a marker of insulin resistance, the results are consistent with the hypothesis that insulin resistance is associated with a higher risk of coronary heart disease mortality. However, it is doubtful that circulating insulin per se is a direct cause of arterial complications. PMID- 1864492 TI - Lack of familial predisposition to cardiovascular disease in type 1 (insulin dependent) diabetic patients with nephropathy. AB - A familial predisposition has been proposed as a major determinant of the increased morbidity and mortality from cardiovascular disease demonstrated in Type 1 (insulin-dependent) diabetic patients with nephropathy. We assessed this concept by studying 91 parents of Type 1 diabetic patients with nephropathy and 94 parents of aged-matched Type 1 diabetic patients with normoalbuminuria. The two groups of parents were of a similar age (58 +/- 8 vs 58 +/- 7 years). The prevalence (%) of death and cardiovascular diseases (World Health Organisation questionnaire) was 10 (4-18)% and 12 (6-21)% in parents of nephropathic patients compared to 8 (3-16)% and 13 (6-23)% in parents of normoalbuminuric Type 1 diabetic patients. The frequency of risk factors for cardiovascular disease were about the same in both groups of parents. Microalbuminuria was found in 5% and 11%, hypercholesterolaemia (greater than 6.5 mmol/l) in 25% and 26% and smokers constituted 40% and 34% of parents of patients with and without proteinuria, respectively. A familial predisposition to cardiovascular disease cannot explain the increased morbidity and mortality from cardiovascular disease in young patients with diabetic nephropathy. PMID- 1864493 TI - Effect of potassium channel blocking agents on the actions of phenylephrine in rabbit taenia caeci. AB - The effects of tetraethylammonium, apamin, 4-aminopyridine and holding potential on the phenylephrine-evoked outward currents in dispersed smooth muscle cells of the rabbit taenia caeci were analyzed using the whole cell patch clamp method. Phenylephrine (10 mumol/l) under the double sucrose gap condition, substantially hyperpolarized the smooth muscle membrane and reduced the input membrane resistance. This concentration of phenylephrine enhanced the frequency and amplitude of spontaneous transient outward currents (s.t.o.c.s) and elicited a low amplitude sustained outward current which were voltage and temperature dependent. In addition, phenylephrine (10 mumol/l) reduced the outward current evoked by voltage steps. Tetratehylammonium (1-5 mmol/l) attenuated the depolarization-evoked outward current, blocked the appearance of s.t.o.c.s, and fully abolished the phenylehrine induced changes in membrane currents. Apamin (0.1-10 mumol/l) only slightly affected the evoked outward current and s.t.o.c.s. However apamin did not change the phenylephrine-induced outward currents. Pretreatment with 4-aminopyridine (0.5-2 mmol/l) did not reduce the phenylephrine induced sustained outward current and s.t.o.c.s but prevented the phenylephrine induced reduction of the depolarization-evoked outward current. These results are in favour of assumption that the phenylephrine induced hyperpolarization and reduction in the input membrane resistance are consequences of an enhanced potassium current via tetraethylammonium-sensitive, apamin and 4-aminopyridine resistant potassium channels. PMID- 1864494 TI - Factors controlling the intracellular concentration of calcium and the spontaneous activity of the ureter. AB - The role of the electrogenic Na(+)-Ca(2+)-exchange mechanism in regulating the spike activity of the ureter was studied. The ureter cells were shown to be capable of generating action potentials (AP) in sodium-free Krebs solution. The time during which the spikes are generated is in exponential dependence on the concentration of calcium ions in the medium, [Ca2+]o within 2.5 to 15 mmol/l. Simultaneously with the generation of the spikes, accumulation of calcium in the muscles is observed, proportional to the increase of [Ca2+]o. The addition of as little as 20 mmol/l Na+ or Li+ ions into the solution restores the prolonged electrical activity of the ureter. Under these conditions, the decrease of intracellular Ca2+ within 5 min was more than two times larger as compared with that in sodium-free medium. Upon substituting Ba2+ ions for Ca2+ ions in Krebs solution AP are generated within an interval which was the longer the higher the Ba2+ concentration in the medium. Li+ ions can replace Na+ ions in maintaining AP and in extruding calcium from the cell. It is supposed that the generation of the stable spike activity of the ureter depends on the functioning of Na(+)-Ca(2+) exchange mechanism. PMID- 1864495 TI - Phototactic responses of Chlamydomonas eugametos gametes before and after fusion. AB - The phototactic behavior of Chlamydomonas eugametos gametes and vis-a-vis pairs was quantitated using a fully automated, computer-controlled microvideo image analysis system. Two different mt- (mating type minus) and one mt+ (mating type plus) strain, together with the two combinations of pairs were studied. One mt- strain of dark-adapted gametes was non-phototactic while the others were positively phototactic at all effective intensities of white light. The mt+ strain exhibited one of the strongest positive responses that has so far been reported in algae (r-values greater than 0.7). After sexual fusion, the mt+ cell powers the swimming vis-a-vis pair. Its phototactic behavior reversed on fusion, with the pairs swimming away from all effective light intensities, irrespective of whether its partner was formerly phototactic or not. However, when adapted to the dark for an hour or more, vis-a-vis pairs swam positively to the light. The ecological consequence could be that pairs settle and develop into zygotes under intermediate light intensities or at light-dark interfaces. PMID- 1864496 TI - A self-assembled pigmented BLM on a platinum support: the light-induced electrical effects. AB - The light-induced voltage and current changes under continuous illumination have been investigated in pigmented self-assembled lipid bilayer membranes deposited on a platinum electrode. Such self-organized pigmented bilayer-platinum system containing Zn-Phthalocyanine (ZnPc) as a photosensitizer and glycerol-dioleate (GDO) as a bilayer forming solution has been found to shift its electrode potential to more positive value on light irradiation as well as to increase the cathodic current across the membrane. The results indicate a direct electron transfer from the platinum electrode to hydrogen ion in the electrolyte solution. Furthermore, it has also been demonstrated a dramatic increase of the photocurrent over the time course of BLM formation visualizing a role of the bulk quenching processes which are significantly diminished in thin bilayer membrane. PMID- 1864497 TI - What are the principal enzymes oxidizing the xenobiotics in plants: cytochromes P 450 or peroxidases? (A hypothesis). AB - Effectively no information is available at present concerning the enzymes which directly participate in the in vivo oxidation of xenobiotics in plants. Based on the known data a hypothesis is presented suggesting that only a minor part of the oxidation of xenobiotics in plants may be catalyzed by cytochrome P-450, the majority of xenobiotics being oxidized by plant peroxidases. PMID- 1864498 TI - Effects of sodium gradient on the cytosolic free Ca2+ and contractility of the pregnant rat myometrium smooth muscle. PMID- 1864499 TI - Escherichia coli RecBCD enzyme: inducible overproduction and reconstitution of the ATP-dependent deoxyribonuclease from purified subunits. AB - The intracellular levels of the Escherichia coli RecBCD proteins have been amplified by fusing the recBCD genes to the strong tac promoter/operator in the expression vector, pKK223-3. The overproduced proteins occur at levels amounting to approx. 10% of total cellular protein. Strains harbouring these overexpression plasmids have been used to purify the RecB. RecC and RecD protein subunits, as well as the RecBCD holoenzyme. The individually purified protein subunits can be used to reconstitute the ATP-dependent DNase activity of the RecBCD enzyme. PMID- 1864500 TI - Cloning and expression in Escherichia coli of three lipase-encoding genes from the psychrotrophic antarctic strain Moraxella TA144. AB - The cloning and expression of genes from a psychrotrophic bacterium in a mesophilic host are described. Three lipase (Lip)-encoding genes (lip) from the antarctic psychrotroph, Moraxella TA144, were cloned by inserting Sau3AI generated DNA fragments into the BamHI site of the pSP73 plasmid vector. To prevent heat denaturation of the gene product, the screening procedure on agar plates containing an emulsified lipid involved growing of Escherichia coli recombinant colonies at 25 degrees C followed by incubation at 0 degree C. The three recombinant (reLip) were cell-associated and differed by their respective specificity towards p-nitrophenyl esters of various aliphatic chain lengths. These cloned reLip conserved the main character of the wild-type enzymes, i.e. a dramatic shift of the optimal temperature of activity towards low temperatures and pronounced heat lability. PMID- 1864501 TI - Structure and organization of the gas vesicle gene cluster on the Halobacterium halobium plasmid pNRC100. AB - Halobacterium halobium strain NRC-1 contains intracellular gas-filled vesicles (GVs) that confer buoyancy to the cells. Cloning of the major GV protein (GvpA) encoding gene, gvpA, and analysis of GV-deficient mutants (Vac-) of H. halobium led to the identification of a region of a 200-kb plasmid, pNRC100, important for GV synthesis. We report here the nucleotide sequence of an 8520-bp region which, including gvpA, contains twelve open reading frames (ORFs) that are organized into two divergent transcription units, gvpAC oriented rightward, and gvpD, E, F, G, H, I, J, K, L, and M located upstream from gvpAC and oriented leftward. Insertions into the gvpA promoter and gvpD and E resulted in the Vac- phenotype. The overall gene organization is highly compact with the end of one ORF overlapping with the beginning of the next in most cases. The gene cluster is bracketed by two ISH8 element copies in inverted orientation, an organization suggestive of a composite transposon. Comparison of predicted amino acid sequences showed homology between GvpA, and the gvpJ and gvpM putative gene products. The putative gvpC gene product contains eight copies of an imperfectly repeated sequence with similarity to repeats in a cyanobacterial GvpC plus a highly acidic C-terminal region not found in the cyanobacterial homologue. PMID- 1864502 TI - Sequence and expression in Escherichia coli of a Mycoplasma hominis gene encoding elongation factor Tu. AB - We describe the molecular cloning and the complete nucleotide (nt) sequence of a Mycoplasma hominis gene common to a broad range of Mycoplasma species, as defined by hybridization analysis with the cloned gene. Production of M. hominis protein in Escherichia coli was assayed by use of a monoclonal antibody. The nt sequence analysis revealed a 1194-bp open reading frame that could encode a 43 516-Da protein. Computer-aided sequence comparison indicated that the gene codes for elongation factor Tu. PMID- 1864503 TI - The adenylyl cyclase-encoding gene from Saccharomyces kluyveri. AB - The gene encoding adenylyl cyclase (CYR) from Saccharomyces kluyveri has been cloned. Comparison of the predicted amino acid sequence of this protein with the Schizosaccharomyces pombe and Saccharomyces cerevisiae CYRs revealed homology between different structural and putative functional domains that suggest a high degree of conservation in the function and regulation of these proteins. PMID- 1864504 TI - Plasmids with easily excisable cat gene cartridges. AB - New cat-cassette-containing vectors based on kanamycin-resistance-encoding plasmids, pHSG298/299, were constructed. They were designed to facilitate the subcloning of the promoterless cat gene into frequently used plasmids, including those with an ampicillin-resistance marker. In plasmids pCAT10-pCAT40, the cat gene cartridges are flanked by polylinker sequences and can be excised by double digestion with pairs of appropriate restriction enzymes. Translation stop condons in all three reading frames are located upstream from the AUG start codon of the pCAT40 cartridge; the latter can also be excised by a single digestion with the enzymes, SalI, PstI, or HindIII. PMID- 1864505 TI - Homology between proteins controlling Streptomyces fradiae tylosin resistance and ATP-binding transport. AB - A tylosin(Ty)-producing strain of Streptomyces fradiae contains at least three genes, tlrA, tlrB, tlrC, specifying resistance to Ty (TyR). The complete nucleotide sequence of the TyR-encoding gene, tlrC, and the transcription start point of the gene were determined. The sequence contains an open reading frame coding for a protein of 548 amino acids (aa) with an Mr of 59129. The TlrC protein was identified by expression of the cloned gene by in vitro coupled transcription and translation in cell-free extracts derived from Streptomyces lividans. The N- and C-terminal halves of TlrC share extensive homology, suggesting that the protein evolved through tandem gene duplication. Each half of the deduced TlrC aa sequence also shows significant homology to numerous eukaryotic and prokaryotic membrane-associated, active-transport protein subunits. The homologous proteins include examples from the systems responsible for efflux of cytotoxic drugs from multidrug-resistant human cells and for export of hemolysin from Escherichia coli. The greatest similarity to TlrC is in regions containing the ATP-binding sites found in these proteins. These results suggest a role for the tlrC gene product as part of a multiple component, ATP-dependent transport system for the active excretion of Ty from the producing organism. PMID- 1864506 TI - Characterization of phosphinothricin acetyltransferase and C-terminal enzymatically active fusion proteins. AB - Enhanced expression of the bialaphos resistance (bar) from Streptomyces hygroscopicus, which confers resistance to the herbicides bialaphos and phosphinothricin (PPT), has been obtained in Escherichia coli using a vector system based on translational coupling. The gene product, PPT acetyltransferase, was purified to homogeneity and its enzymatic properties were analyzed. Hybrid gene constructs with gene fragments fused to the 3'-terminus of bar yield fusion proteins having acetyltransferase activity, with a Michaelis constant for the PPT substrate comparable to the unmodified enzyme. The bar gene represents a selectable and assayable reporter gene especially suitable for 3'-terminal gene fusions. PMID- 1864507 TI - Cloning, disruption and sequence of the gene encoding yeast C-5 sterol desaturase. AB - The ERG3 gene from Saccharomyces cerevisiae has been cloned by complementation of an erg3-2 mutation. ERG3 is the putative gene encoding the C-5 sterol desaturase required for ergosterol biosynthesis. The functional gene has been localized on a 2.5-kb HindIII-BamHI fragment containing an open reading frame comprising 365 amino acids. Gene disruption resulting from a deletion/substitution demonstrates that ERG3 is not essential for cell viability or the sparking function. PMID- 1864508 TI - Characterization of CARE-1: Candida albicans repetitive element-1. AB - A middle repetitive DNA element, Candida albicans repetitive element-1 (CARE-1) has been isolated from the pathogenic yeast C. albicans. CARE-1 appears to be species-specific and constitutes approx. 0.045% of total C. albicans DNA, or a reiteration frequency of about two to twelve copies per haploid genome. The CARE 1 element has been detected on several C. albicans chromosomes separated by field inversion gel electrophoresis, suggesting that the element is dispersed. Interstrain variation was observed in the number and distribution of hybridizing bands. The element is well conserved, since no nucleotide (nt) heterogeneity was observed when the sequences of two CARE-1 family members isolated from two different chromosomes (A and B) of C. albicans were compared. CARE-1 possesses 467 bp and is characterized by several stretches of A's and T's, short direct repeats and shows no significant homology to any known nt sequence. PMID- 1864509 TI - Tandem arrangement of tRNA(Asp)-encoding genes in Phytophthora spp. AB - We have cloned a region of repetitive DNA from the phytopathogenic fungus, Phytophthora parasitica. The cloned region consists of 17 highly homologous units arranged in tandem. The consensus sequence is 562 bp long and carries the information for a tRNA(Asp). All sequence motifs required for efficient RNA polymerase III transcription are present, and the tRNA derived from the nucleotide sequence is able to form a complete cloverleaf structure with high homology to previously characterized tRNA(Asp) molecules. The isolated tRNA(Asp) gene cluster is located at a distance of 20 kb from the TRP1 gene of P. parasitica. It comprises about 0.1% of the total genomic DNA. Similar clusters were detected in four other Phytophthora species. PMID- 1864510 TI - Isolation of two genes encoding putative protein kinases regulated during Dictyostelium discoideum development. AB - Two Dictyostelium discoideum protein kinase(PK)-encoding cDNAs (Dd PK1 and Dd PK2) have been isolated by hybridization with an oligodeoxyribonucleotide derived from a highly conserved region of eukaryotic PKs. The two nucleotide (nt) sequences encode new putative serine/threonine-specific PKs. Dd PK1 is a partial cDNA covering the entire catalytic domain. The derived amino acid (aa) sequence is about 30% identical to both cAMP-dependent protein kinase (cAPK) and protein kinase C. The Dd PK2 sequence was extended through the isolation of a genomic fragment encoding a complete putative protein. A single intron is present, as deduced from sequence comparison with the cDNA. The catalytic domain appears more closely related to the catalytic subunit of cAPK (54% sequence identity). However, our nt sequence potentially codes for a much larger protein (648 vs. about 350 aa for most cAPKs) with a N-terminal half containing long homopolymers of threonines, glutamines and asparagines. Similar repeats occur at the C terminus of Dd PK1, Dd PK1 is expressed in vegetatively growing cells and during development. Dd PK1 RNA decreases after 6 h of starvation to re-accumulate once the cells have aggregated. Dd PK2 transcripts, present at a low amount in growing cells, rise upon starvation. A switch to a shorter form of transcripts occurs between 3 and 6 h into development. PMID- 1864511 TI - A general method for introducing a series of mutations into cloned DNA using the polymerase chain reaction. AB - A simple and fast method for introducing a series of mutations in cloned DNA has been developed. The polymerase chain reaction (PCR) has been used for site directed mutagenesis. Because mutations can be introduced only within the primer sequences used for PCR, a suitable restriction site in the vicinity of the mutated nucleotide is required to permit recloning. Several methods have been devised to overcome this limitation. Our present method is a modification of the overlap extension method [Ho et al., Gene 77 (1989) 51-57], and has some advantages over this and other published methods. In our method, three common primers and a series of primers specific for various mutations are chemically synthesized. Once the proper oligodeoxyribonucleotides are selected as common primers, each mutation requires only one additional primer. Therefore, this method is very useful for introducing many mutations in various sites of the target DNA. We describe our protocol for the site-directed mutagenesis and an example of the introduction of several mutations in the hen egg-white lysozyme encoding gene. PMID- 1864512 TI - Cloning the BstVI restriction-modification system in Escherichia coli. AB - A standard DNA modification methyltransferase (MTase) selection protocol was followed to clone the BstVI restriction and modification system from Bacillus stearothermophilus in Escherichia coli. Both genes were contained in a 4.4-kb EcoRI fragment from B. stearothermophilus V chromosomal DNA. The heterologous expression of these genes did not depend on their orientation in the vector, suggesting that the genes are expressed in E. coli under the control of promoters located on the cloned fragment. Subcloning experiments demonstrated that the bstVIR gene was expressed in the absence of its cognate MTase. PMID- 1864513 TI - A family of Corynebacterium glutamicum/Escherichia coli shuttle vectors for cloning, controlled gene expression, and promoter probing. AB - A new family of vectors including cloning vectors (pEK0; pEC5), an expression vector (pEKEx1), and promoter probe vectors (pEKpllacZ; pEKplCm), has been constructed. All these shuttle vectors are based on the replication origins of the corynebacterial pBL1 and the Escherichia coli ColE1 plasmids, and thus are able to replicate in Corynebacterium glutamicum and E. coli. Plasmids pEK0 and pEC5 carry multiple restriction sites useful for gene cloning and the kanamycin- or chloramphenicol-resistance-encoding gene from Tn903 or from Tn9, respectively. In C. glutamicum, both vectors are compatible with vectors containing the corynebacterial pHM1519 replicon. Based on plasmid pEK0, the expression vector pEKEx1 was developed to allow for isopropyl-beta-D-thiogalactopyranoside inducible expression of inserted genes in C. glutamicum and E. coli. Also based on pEK0, the promoter probe vectors pEKpllacZ and pEKplCm were constructed to carry the promoterless lacZ or cat reporter genes downstream from useful cloning sites, for assaying the transcriptional activity of cloned fragments. PMID- 1864514 TI - Shuttle vectors containing a multiple cloning site and a lacZ alpha gene for conjugal transfer of DNA from Escherichia coli to gram-positive bacteria. AB - The mobilizable shuttle cloning vectors, pAT18 and pAT19, are composed of: (i) the replication origins of pUC and of the broad-host-range enterococcal plasmid pAM beta 1; (ii) an erythromycin-resistance-encoding gene expressed in Gram- and Gram+ bacteria; (iii) the transfer origin of the IncP plasmid RK2; and (iv) the multiple cloning site and the lacZ alpha reporter gene of pUC18 (pAT18) and pUC19 (pAT19). These 6.6-kb plasmids contain ten unique cloning sites that allow screening of derivatives containing DNA inserts by alpha-complementation in Escherichia coli carrying the lacZ delta M15 deletion, and can be efficiently mobilized by self-transferable IncP plasmids co-resident in the E. coli donors. Plasmids pAT18, pAT19 and recombinant derivatives have been successfully transferred by conjugation from E. coli to Bacillus subtilis, Bacillus thuringiensis, Listeria monocytogenes, Enterococcus faecalis, Lactococcus lactis, and Staphylococcus aureus at frequencies ranging from 10(-6) to 10(-9). The presence of a restriction system in the recipient dramatically affects (by three orders of magnitude) the efficiency of conjugal transfer of these vectors from E. coli to Gram+ bacteria. PMID- 1864515 TI - An agenda to extend and enhance life. PMID- 1864516 TI - AIDS: older patients are also candidates for HIV infection. PMID- 1864517 TI - History-taking in the elderly: obtaining useful information. AB - Although the medical history in the average adult can approach a diagnostic yield of 90%, its utility in geriatric patients is often much lower. Potential barriers to communication with the elderly include cognitive, behavioral, and physical problems. This article suggests techniques the primary care physician can use to overcome these obstacles and get the maximum diagnostic information from the patient history. PMID- 1864518 TI - Special considerations in the physical exam of older patients. AB - For diagnostic utility, aspects of the standard physical examination are modified for elderly patients. Special attention is paid to problems that interfere with function, such as gait disorders, incontinence, and hearing and visual loss. Certain findings in cardiac and pulmonary examinations of the elderly require different interpretations. The examination should include the head and neck, chest, back, abdomen, breasts and pelvic area in women, prostate in men, extremities, and skin, as well as mental status. A number of diagnostic maneuvers are used to distinguish changes of normal aging from those associated with disease. PMID- 1864519 TI - The neurology of aging: normal versus pathologic change. AB - Mild changes in neurologic function occur with aging but generally do not substantially interfere with everyday activities unless disease intervenes. Not infrequently, older adults experience minor impairment in memory, speed of cognitive processing, sleep, vision and hearing, vibratory sense in the lower extremities, and gait and posture. In general, these changes correspond with age associated neuroanatomic changes (eg, diminished brain weight), but there is wide variability in the extent to which these changes occur. Often, "normal" neurologic changes are difficult to distinguish from impairment associated with disease. PMID- 1864520 TI - 'Eldercare' goal: integrate health, social needs. AB - New national campaign nurtures complementary programs to address a wide range of elderly care issues. PMID- 1864521 TI - Oxidative stress status: an introduction. PMID- 1864522 TI - Oxidative stress status and cancer: methodology applicable for human studies. AB - There is convincing evidence to suggest that oxidative stress status might be involved in the etiology of cancer, but relatively little direct human data are available. The National Cancer Institute recently sponsored a workshop evaluating methodology for measuring oxidative stress status with potential application to human studies. PMID- 1864523 TI - The possible role of lipid peroxidation in breast cancer risk. AB - Breast cancer remains the commonest cause of death from cancer in women in most of the Western world. There is considerable evidence that breast cancer risk is influenced by environmental factors and can therefore potentially be modified. In this paper we describe evidence suggesting a relationship of lipid peroxidation to breast cancer risk, and propose that the method used to generate this information might usefully be applied to other disease states, and make some suggestions for further work. We have compared the urinary excretion of the mutagen malonaldehyde (MDA) in premenopausal women at different risks for breast cancer as determined by the appearance of the breast parenchyma on mammography. MDA was measured in 24-h urine samples from both groups and excretion in 30 women with mammographic dysplasia (high risk) was found to be approximately double that of 16 women without these radiological changes (p less than 0.02). These results suggest that mammographic dysplasia may be associated with lipid peroxidation. Further study of environmental factors associated with states that precede the development of breast and other cancers may lead to the identification of factors that can be modified and that may prevent the development of malignant disease. PMID- 1864524 TI - In vivo breath alkane as an index of lipid peroxidation. AB - Interaction of active oxygen species with polyunsaturated fatty acids (PUFA) results in a series of reactions called lipid peroxidation. During the process of peroxidation of polyunsaturated fatty acids there is a scission of an alkane fragment extending from the methyl end of the fatty acid to the double bond. Thus, with a w-6 polyunsaturated fatty acid pentane is released, and with a w-3 polyunsaturated fatty acid ethane is released. These hydrocarbons are distributed in the body, partly metabolized, and excreted in the breath, making it possible to estimate the magnitude of in vivo lipid peroxidation by measuring pentane and ethane exhaled in breath. Advantages of this method are discussed as well as limitations and possible sources of error. PMID- 1864525 TI - An overview of the relationship between oxidative stress and chemical carcinogenesis. AB - Substantial experimental evidence exists which implicates both oxygen- and organic-free radical intermediates in the multiple stages of chemical carcinogenesis. This overview summarizes some of the biochemical and molecular interactions which could result from a state of oxidative stress following the generation of free radical intermediates from chemical carcinogens in target cells. Evidence for a relationship between carcinogenesis and inflammation as a mediator of oxidative stress is also discussed. Understanding the interactions of radical intermediates with target biomolecules should lead to the development of relevant biomarkers of these interactions as well as rational chemoprotective strategies with antioxidants or other radical detoxifiers for the prevention of neoplasia. PMID- 1864526 TI - Correlations and apparent contradictions in assessment of oxidant stress status in vivo. AB - Oxidative modifications of biological molecules are essential, but uncontrolled or excessive oxidative activities appear to contribute to many disease states. The mechanisms through which excess oxidant activities cause injury have been studied most extensively for acute responses, particularly for drug-induced tissue damage and cell death, but substantial evidence suggests that chronically elevated oxidative activity may contribute to the development of diseases such as cancer. It is important that the correlation between oxidant stress status and cancer risk be examined directly in humans. A number of methods have been developed for assessing oxidant activities by measuring oxidized products in biological systems, but cross-comparison studies of these different methods are needed. In studies of mechanisms of acute hepatotoxicity, assessments of oxidant stress responses by different analytical methods often have provided data that appear at first glance to be contradictory. Marked oxidant stress responses may be indicated by one or more methods of analysis despite the lack of detectable change in other parameters, whereas in a second experimental model the responses may be reversed. These observations emphasize the need to integrate different analytical approaches into the assessment of oxidant activity in vivo and illustrate the importance for developing a better understanding of the chemical and physiological mechanisms through which the analytical methodologies are related. PMID- 1864527 TI - Determinants of ileoanal pouch function. PMID- 1864528 TI - Symptomatic gastro-oesophageal reflux, abnormal oesophageal acid exposure, and mucosal acid sensitivity are three separate, though related, aspects of gastro oesophageal reflux disease. AB - The Bernstein test has been used as a test of oesophageal acid sensitivity for over 30 years but its clinical value has been challenged by the advent of ambulatory pH monitoring. Furthermore, the relation between mucosal acid sensitivity, symptomatic reflux, and abnormal oesophageal acid exposure time is unclear. This study examined the relation between these three parameters in patients referred for pH monitoring with unexplained chest pain or heartburn. Fifty consecutive patients were studied - nine with non-cardiac chest pain and 41 with a history of heartburn. Symptomatic reflux was defined as a greater than or equal to 50% temporal association between pain episodes and reflux events (pH less than 4) during pH monitoring. A positive acid perfusion test (in which the patient's usual symptoms were evoked by acid, though not saline) had a 100% sensitivity, 73% specificity, and 81% accuracy for the detection of symptomatic reflux. All 10 patients with symptomatic reflux during pH monitoring had evidence of mucosal acid sensitivity. A negative acid perfusion test made symptomatic reflux unlikely. However, symptomatic reflux or a positive acid perfusion test, or both, were found in some patients with a normal oesophageal acid exposure time during pH monitoring. Mucosal acid sensitivity, abnormal oesophageal acid exposure time, and symptomatic reflux should be regarded as separate, though related aspects of reflux disease. The Bernstein test is simple, safe, and easily performed. A positive test helps to identify an oesophageal cause of symptoms, particularly in patients in whom other aspects of 'gastro-oesophageal reflux disease' are absent, or who do not have symptoms during pH monitoring. PMID- 1864529 TI - Does body posture affect the incidence and mechanism of gastro-oesophageal reflux? AB - We studied eight patients with gastro-oesophageal reflux disease to compare the frequency and mechanism of reflux in the upright and supine positions. Simultaneous oesophageal manometry and pH studies were performed on two separate days in each subject in the fasting and postprandial periods. The frequency of reflux tended to be higher in the upright position. The most prevalent mechanism of reflux in either position was transient relaxation of the lower oesophageal sphincter. The frequency of transient lower oesophageal sphincter relaxation was higher in the upright than in the supine position. There was no difference in the total reflux time, acid clearance time, and number of reflux episodes lasting longer than five minutes in the two positions. We suggest that daytime reflux (upright) may be as important as night time (supine) reflux in the pathogenesis of reflux oesophagitis and needs to be considered when treating patients with reflux disease. PMID- 1864530 TI - Gastritis due to spiral shaped bacteria other than Helicobacter pylori: clinical, histological, and ultrastructural findings. AB - An intensive histological search for Helicobacter pylori in gastric biopsy specimens has led to the detection of other spiral shaped bacteria in the human gastric mucosa. The clinical and morphological findings of 39 cases (0.25% of all gastric biopsies performed in the observation period) are reported for 34 patients (87.2%) complaining of upper abdominal discomfort. Five patients (12.8%) had chronic gastritis and 34 (87.2%) chronic active gastritis. The organisms were seen by light microscopy deep in the gastric foveolae and intracellularly. The scanning and transmission electron microscopic findings show bacteria which invade and damage gastric mucosal cells. These organisms are similar to the spiral shaped bacteria found in the stomachs of cats and dogs and non-human primates. In eight patients organisms were not detected after four weeks of treatment with bismuth salts. The disappearance of the organisms coincided with resolution of the chronic active gastritis and the symptoms. PMID- 1864531 TI - Can transcutaneous recordings detect gastric electrical abnormalities? AB - The ability of transcutaneous recordings of gastric electrical activity to detect gastric electrical abnormalities was determined by simultaneous measurements of gastric electrical activity with surgically implanted serosal electrodes and cutaneous electrodes in six patients undergoing abdominal operations. Transient abnormalities in gastric electrical activity were seen in five of the six patients during the postoperative period. Recognition of normal gastric electrical activity by visual analysis was possible 67% of the time and with computer analysis 95% of the time. Ninety four per cent of abnormalities in frequency were detected by visual analysis and 93.7% by computer analysis. Abnormalities involving a loss of coupling, however, were not recognised by transcutaneous recordings. Transcutaneous recordings of gastric electrical activity assessed by computer analysis can usually recognise normal gastric electrical activity and tachygastria. Current techniques, however, are unable to detect abnormalities in electrical coupling. PMID- 1864532 TI - Maintenance treatment of duodenal ulceration: ranitidine 300 mg at night is better than 150 mg in cigarette smokers. AB - Two hundred patients received either ranitidine 150 mg or 300 mg at night for 18 months to prevent duodenal ulcer relapse. Recurrence rates were lower in patients receiving the higher dose of ranitidine (3.1% v 9.7%, p = 0.78; 6.5% v 16.7%, p = 0.037; and 8.9% v 17.0%, p = 0.121 at six, 12, and 18 months respectively). In patients receiving ranitidine 150 mg, recurrences were significantly more common in smokers than non-smokers after 12 and 18 months, while in patients receiving ranitidine 300 mg recurrence rates were similar in smokers and non-smokers. Ranitidine 300 mg at night abolishes the adverse effect of smoking observed during maintenance treatment with ranitidine 150 mg at night and may therefore be an appropriate maintenance dose for smokers who relapse during standard dose maintenance treatment. PMID- 1864533 TI - Enteropathogenic Escherichia coli and life threatening chronic diarrhoea. AB - Enteropathogenic Escherichia coli (EPEC) infection is not generally thought to cause severe diarrhoea after the neonatal period. Patients admitted to Queen Elizabeth Hospital for Children over the three years (1984-7) with diarrhoea and EPEC infection were reviewed. Clinical details, features of small intestinal mucosa, and treatment were recorded in those who developed chronic diarrhoea with failure to thrive. Twenty six children with EPEC required hospital admission for diarrhoea and six of these (23%) developed chronic diarrhoea. In contrast only two (5%) of 42 with other serogroups of E coli (p less than 0.01) and 28 (4%) of 764 children without EPEC admitted with acute diarrhoea developed chronic symptoms (p less than 0.01). EPEC serogroups detected in the stool of the six children with chronic diarrhoea were 0128 in three, 0114 in two, and 0119 in one. The patients' clinical characteristics were: previous good health, no significant immunodeficiency, age 4-10 months, foreign travel (three of six), severe life threatening secretory diarrhoea from 0.5 to 1.5 1 per day (four of six), small intestinal enteropathy (five of six) three of whom showed mucosal adherent, non invasive E coli of the same serotype as that in the stool, in association with microvillous loss and pedestal formation. All were treated with hypoallergenic feeds, two with parenteral nutrition, and three with parenteral antibiotics. All eventually recovered. EPEC infection is a common treatable cause of life threatening chronic diarrhoea in infancy. PMID- 1864534 TI - Observations on the Kveim reaction using an animal model of granulomatous bowel disease. AB - Striking differences were observed between the visceral and cutaneous responses after tests with validated Kveim and normal spleen suspensions in a guinea pig model of granulomatous bowel disease. Five of six animals sensitised with BCG showed positive responses at the ileal Kveim test site whereas all six had negative cutaneous Kveim tests. Conversely, two of six animals sensitised with irradiated Mycobacterium leprae showed positive cutaneous Kveim tests and only one a positive response in the ascending colon. All six showed negative responses at the ileal Kveim test site. No positive visceral or cutaneous responses were observed in either group of animals after tests with normal spleen suspension. These findings are discussed in relation to the positive Kveim responses previously reported among patients with Crohn's disease, tuberculoid and lepromatous leprosy, and among seemingly healthy BCG vaccinated subjects. The findings provide further evidence in support of a possible mycobacterial aetiology for sarcoidosis and Crohn's disease. PMID- 1864535 TI - Serum and tissue autoantibodies to colonic epithelium in ulcerative colitis. AB - Sera and colonic tissue-bound immunoglobulin extracts from patients with ulcerative colitis and disease controls were examined immunohistochemically and by killer cell cytotoxicity assay for the presence of anticolonic epithelial autoantibodies. IgG yields in the tissue extracts from patients with colitis and control subjects were similar, and the extracts were uniformly autoantibody negative. Of 41 sera from patients with inflammatory bowel disease, 'classical' anticolon antibody was present in 41% and was commoner in patients with sclerosing cholangitis. Cytotoxic anticolon antibody was present in 20% overall and was strongly associated with disease activity; it did not correlate with the presence of 'classical' anticolon antibody. The heterogeneous and non-universal antiepithelial autoantibody response and the failure to detect tissue bound autoantibody in vivo argue against the hypothesis that humoral autoimmunity is of major importance in the pathogenesis of ulcerative colitis. PMID- 1864536 TI - Colorectal cancer in ulcerative colitis. Influence of anatomical extent and age at onset on colitis-cancer interval. AB - We have examined the age at onset of both ulcerative colitis and colitis associated colorectal cancer in 100 patients seen at Mount Sinai Hospital between 1959 and 1988. There were 85 patients with extensive colitis and 15 with left sided colitis. There was a strong direct correlation between the age at onset of ulcerative colitis and age at diagnosis of cancer (p less than 0.0001); this correlation was found both in patients with extensive colitis (p less than 0.0001) and in those with left sided colitis (p less than 0.005). Patients with left sided colitis developed both their colitis and their cancers about a decade later than did those with extensive disease, but the mean duration of colitis before diagnosis of cancer was virtually the same (about 21 years) in both groups, irrespective of the age at onset of disease. PMID- 1864537 TI - Microscopic activity in ulcerative colitis: what does it mean? AB - To determine the prognostic importance of microscopic rectal inflammation we followed up 82 patients (aged 21 to 78 years, 44 men) with chronic quiescent ulcerative colitis over 12 months. At trial entry each patient underwent a rectal biopsy and sections were graded independently by two histopathologists. A chronic inflammatory cell infiltrate of varying severity was present in all biopsy specimens, and 58% had crypt architectural irregularities. In addition, 32% had evidence of acute inflammatory activity: 28% acute inflammatory cell infiltrate, 11% crypt abscesses, and 22% mucin depletion. Agreement between the two histopathologists for the presence of each of these features was 94% (90-98%). During the 12 month follow up 27 patients (33%) relapsed after a mean interval of 18 weeks (range 3-44 weeks). Relapse rates were unrelated to duration or extent of disease or to the type of maintenance drug treatment. In patients with an acute inflammatory cell infiltrate 52% relapsed, whereas in the absence of such an infiltrate only 25% relapsed (p = 0.02). Similarly, relapse rates were higher in the presence of crypt abscesses (78% v 27%, p less than 0.005), mucin depletion (56% v p less than 0.02), and breaches in the surface epithelium (75% v 31%, p = 0.1). The presence of a chronic inflammatory cell infiltrate or crypt architectural irregularities, however, bore no relation to the frequency of colitis relapse. PMID- 1864538 TI - Prevalence of proximal faecal stasis in active ulcerative colitis. AB - Proximal faecal stasis may occur when faecal matter accumulates in the uninflamed colon above an area of active ulcerative colitis. This phenomenon is thought to be the cause of symptoms in some patients with distal disease. It is not known, however, how often patients with active distal colitis exhibit slow colonic transit. Fifty two consecutive patients with active ulcerative colitis each ingested 10 radio-opaque markers nightly for 14 days. Minimum colonic transit times were derived from counts of retained markers shown by plain abdominal radiography on the 15th day. The transit times for each patient were related to their disease extent and bowel frequency. Four patients had colonic transit times greater than one week and two others had evidence of relative stasis. The results indicate that approximately 10% of attacks of distal colitis are associated with faecal stasis. PMID- 1864539 TI - Morphometric studies in rectal biopsy specimens from patients with ulcerative colitis: effect of oral 5 amino salicylic acid and rectal prednisolone treatment. AB - Morphometric measurements were performed on rectal biopsy specimens from 10 normal control subjects and 33 patients with a relapse of distal ulcerative colitis before and after treatment for four weeks in a double blind controlled trial with oral eudragit S coated 5 amino salicylic acid (n = 12) or rectal prednisolone enemas (n = 15). Measurements were assessed using a computer aided measuring system and a counting technique. When untreated patients were compared with the control group there were significant decreases in the area and height of the surface epithelium, in the area of crypt epithelium, and in the ratios of goblet cells to epithelial cells and of surface epithelium to lamina propria. The vascular and lamina propria areas and the number of intraepithelial polymorphs were increased. Treatment with 5 amino salicylic acid and corticosteroids resulted in similar morphological improvements: there was an increase in the area and height of the surface epithelium and the ratios of surface epithelium to lamina propria and of surface to crypt cell height. The ratio of goblet cells to epithelial cells also increased after treatment, while the numbers of polymorphs in the surface and crypt epithelium and lumen decreased. In conclusion, computerised morphometry is valuable for the assessment of the treatment of patients with ulcerative colitis and that in the doses used both treatments were of similar efficacy. PMID- 1864540 TI - Does bipolar electrocoagulation time affect vessel weld strength? AB - The value of the bipolar electrocoagulator in the haemostasis of bleeding ulcers is controversial. We have therefore investigated the effect of different coagulation times on vessel weld strength achieved by the bipolar device. Welds were then made in vessels of known diameter using a standard 10F endoscopic haemostatic probe at coagulation times of two and 20 seconds. The intravascular temperature achieved at each time was measured. Vessel weld strength achieved by bipolar electrocoagulation was much greater at 20 seconds (approximately twice that at two seconds) and was highly significantly greater at all vessel diameters. There was a gradual reduction in weld strength with increasing vessel diameter, an effect that was seen for both two and 20 seconds of electrocoagulation. Intravascular temperature was significantly higher at 20 seconds than at two seconds. We conclude that vessel weld strength is related to coagulation time and that any future studies comparing the bipolar electrocoagulator with other haemostatic devices should use longer periods of bipolar electrocoagulation and record the coagulation time in order to optimise the clinical value of the device. PMID- 1864541 TI - Binding of kidney bean (Phaseolus vulgaris) isolectins to differentiated human colon carcinoma Caco-2 cells and their effect on cellular metabolism. AB - The binding of Phaseolus vulgaris (PHA) isolectins L4 and E4 to the brush border membrane of differentiated Caco-2 cells was studied and the impact on cellular metabolism and microvilli was assessed. Computer analysis of the data based on binding experiments with peroxidase conjugated isolectins gave mean (SD) values for maximal binding of 2540 (151).10(-9) M for PHA-L4 and 2104 (140).10(-9) M for PHA-E4 per mg of brush border membrane protein. The dissociation constants for L4 and E4 binding were 4.3 (1.4).10(-6) M and 1.1 (0.8).10(-6) M, respectively. Incubation of differentiated Caco-2 cells for 30 minutes with ferritin conjugated PHA isolectins showed that, as indicated by the number of ferritin particles, PHA E4 bound to the microvilli to a greater extent than PHA-L4. Ferritin particles were also localised intracellularly over endocytotic invaginations and vesicles. After incubation for 48 hours with PHA-L4 or PHA-E4, the relative incorporation of precursors for DNA, RNA, and (glyco)protein synthesis into the trichloroacetic acid insoluble fraction of the Caco-2 cells was determined. Both isolectins stimulated the incorporation of thymidine and glucosamine, but neither PHA-L4 nor PHA-E4 were able to influence the incorporation of uridine. With respect to fucose, methionine, and N-acetyl mannosamine, the stimulatory effect remained confined to PHA-E4. Since PHA-L4 and PHA-E4 were tested at the same concentrations, PHA-E4 is more effective than PHA-L4. The changes in the uptake of radioactive precursors were lost after heat inactivation of PHA-E4. Compared with control and PHA-L4 incubated Caco-2 cells, the microvilli of PHA-E4 incubated cells were shortened significantly (p less than 0.01). PMID- 1864542 TI - Amenorrhoea in women with non-alcoholic chronic liver disease. AB - Amenorrhoea is common in women with non-alcoholic chronic liver disease, but little is known about its causes or consequences. We investigated 12 young women with non-alcoholic chronic liver disease and amenorrhoea and compared them with 11 healthy age matched controls studied in the follicular phase of the menstrual cycle. None of the patients had raised serum concentrations of follicle stimulating hormone suggesting primary gonadal failure, but the variance in serum concentrations of testosterone, oestradiol, prolactin, and luteinising hormone were significantly greater in chronic liver disease patients than control subjects (p less than 0.01). Seven of the 12 chronic liver disease patients had low serum luteinising hormone concentrations, and compared with controls these patients also had significantly reduced median values of oestradiol (64 pmol/l), testosterone (1.1 nmol/l), and follicle stimulating hormone, and were significantly underweight as assessed by skinfold thickness measurements (all comparisons p less than 0.025). In the group with chronic liver disease skinfold thickness was significantly correlated with serum luteinising hormone (p less than 0.02). The five patients with normal serum luteinising hormone had higher median values of both oestradiol (237 pmol/l) and testosterone (3.0 nmol/l) than the control subjects (oestradiol: 113 pmol/l, testosterone: 1.9 nmol/l) but were not more obese or hirsute. Amenorrhoea was unrelated to the duration or severity of liver disease. The metacarpal cortical bone area (an index of bone density) was inversely related to the duration of amenorrhoea (p less than 0.02). We conclude that amenorrhoea in women with non-alcoholic chronic liver disease arises from hypothalamic-pituitary dysfunction and can occur at any stage. The hormonal findings in amenorrhoeic chronic live disease patients are not uniform. In some, hypogonadotrophic hypogonadism is related to undernutrition whereas others have normal to high values of luteinising hormone and sex steroids. Prolonged oestrogen deficiency can be a risk factor for osteoporosis in women with chronic liver disease. PMID- 1864543 TI - Confirmation of the efficacy of hepatic tissue iron index in differentiating genetic haemochromatosis from alcoholic liver disease complicated by alcoholic haemosiderosis. AB - The hepatic tissue iron index proposed by Bassett et al was evaluated in 35 patients with homozygous genetic haemochromatosis, 67 patients with alcoholic liver disease, and 18 patients with other forms of chronic liver disease with and without cirrhosis. In patients with cirrhosis hepatic tissue iron concentration reliably differentiated alcoholic liver disease from genetic haemochromatosis. Although mean iron concentration was greater in patients with prefibrotic haemochromatosis than in those with prefibrotic alcoholic liver disease, some overlap occurred and complete differentiation of the two conditions was not possible. This overlap was particularly evident in some young patients with haemochromatosis in whom the tissue iron concentration grade fell in the range commonly seen in alcoholic haemosiderosis. Inability to differentiate early genetic haemochromatosis from alcoholic liver disease complicated by haemosiderosis was also a problem with standard Perls's staining. When the hepatic tissue iron index was calculated (hepatic tissue iron concentration/patient's age in years), clear differentiation of genetic haemochromatosis from both alcoholic liver disease and other forms of chronic liver disease was obtained in both cirrhotic and precirrhotic patients. This study confirms that the hepatic tissue iron index is a useful means of differentiating patients with genetic haemochromatosis from those with alcoholic liver disease. We suggest that biochemical estimation of tissue iron concentration and calculation of the tissue iron index in all patients in whom genetic haemochromatosis is a possible diagnosis will reduce the likelihood of misdiagnosing this as alcoholic liver disease. PMID- 1864544 TI - In vitro comparison of different gall stone dissolution solvents. AB - Extracorporeal shockwave lithotripsy (ESWL) of gall bladder stones leaves residual fragments that need to be dissolved by chemical solvents. In this study we compared the in vitro dissolving capacity of methyl tert-butyl ether (MTBE), mono-octanoin, limonene, and limonene/mono-octanoin (70%/30%). From nine sets of five human gall stones obtained at cholecystectomy, four stones were used for dissolution and the fifth was used for chemical analysis of cholesterol, calcium, and bilirubin contents. Eight sets were cholesterol stones with a mean (SD) cholesterol content of 89.9 (5.6)%. These stones dissolved completely in either solvent, often leaving sand-like debris, with the exception of one stone. MTBE dissolved cholesterol gall stones 100 times faster than mono-octanoin and 10 times faster than limonene or the limonene/mono-octanoin mixture (p less than 0.001). The combination of limonene and mono-octanoin was as effective as limonene alone. Of the four solvents, MTBE is the best one to evaluate for dissolution of residual fragments after ESWL treatment of gall bladder stones. PMID- 1864545 TI - Effect of the cholecystokinin-receptor antagonist lorglumide on pancreatic enzyme secretion stimulated by bombesin, food, and caerulein, giving similar plasma cholecystokinin concentrations in the dog. AB - This study was undertaken to determine the role of cholecystokinin in pancreatic enzyme secretion stimulated by bombesin and a meal by (a) comparing the pancreatic enzyme output during bombesin infusion and after a meal to output during caerulein infusion and (b) comparing the inhibitory effect of the cholecystokinin-receptor antagonist lorglumide (CR-1409) on enzyme output in response to bombesin and food with the response to caerulein. Bombesin (90 pmol/kg per h) and caerulein (30 pmol/kg per h) were infused into seven dogs in doses giving similar plasma cholecystokinin peak increments as a meal (mean (SEM) 6.8 (0.8), 6.3 (1.2), and 5.7 (0.8) pM, respectively), together with either saline or 2 mg/kg per h of lorglumide. A background infusion of synthetic secretin 20.5 pmol/kg per h was given in each experiment. In addition, gastric acid secretion was determined in the experiments with bombesin and caerulein infusion. Pancreatic protein responses to bombesin (1231 (247) mg/h) and food (1430 (220) mg/h) were similar to the responses to caerulein (1249 (201) mg/h). Lorglumide inhibited pancreatic protein output during stimulation with bombesin by 60%, after the meal by 45%, and during caerulein infusion by 68%. Pancreatic bicarbonate output by bombesin, caerulein, and food was inhibited by lorglumide by 28%, 40%, and 38%, respectively. In contrast, lorglumide significantly increased gastric acid secretion from 1.12 to 7.98 mmol/h during bombesin infusion and from 0.52 to 7.62 mmol/h during caerulein infusion. In conclusion, cholecystokinin plays an important part in the stimulation of pancreatic enzyme secretion by bombesin and a meal in conscious dogs and it is involved in the regulation of gastric acid during stimulation by infusions of caerulein and bombesin. PMID- 1864546 TI - Screening for gastrointestinal cancer: an epidemiological review. PMID- 1864547 TI - IgA nephropathy in non-cirrhotic portal hypertension. AB - Renal glomerular changes are a well recognised complication of cirrhosis and are frequently characterised by mesangial IgA deposition. We report a patient with non-cirrhotic portal hypertension who developed IgA nephropathy and a nephrotic syndrome with renal histological changes classically associated with cirrhosis. Splenectomy with resection of a splenic artery aneurysm resulted in remission of the nephrotic syndrome. This case illustrates the factors which contribute to the pathogenesis of IgA nephropathy in liver disease. PMID- 1864548 TI - Sinusoidal portal hypertension in hepatic amyloidosis. AB - Hepatic venous catheterisation and transvenous liver biopsy were performed in five patients with hepatic amyloidosis. In three patients, hepatic venous pressures were normal and histological examination of the liver biopsy specimen showed discrete and sparse perisinusoidal amyloid deposits. In the other two, however, the gradient between wedged and free hepatic venous pressures was increased (12 and 16 mmHg; normal 1-4 mmHg) and amyloid deposits were abundant and diffuse in the Disse's space. This study shows that portal hypertension in patients with hepatic amyloidosis is of the sinusoidal type and is related to the reduction of vascular space of hepatic sinusoids by massive perisinusoidal amyloid deposits. Furthermore, portal hypertension is associated with a poor prognosis in patients with hepatic amyloidosis. PMID- 1864549 TI - Free radicals in colitis. PMID- 1864550 TI - Mononuclear cell (MNC) concentration from the marrow harvest by automatic system. AB - The availability of reliable and standardizable procedures with low contamination risk and less prominent loss in MNC, would solve the existing perplexities about the systematic use of this passage. We tried to experiment Areman's et al protocol that utilizes the CS 3000 blood cell processor without gradient, making some changes and comparing the results with those achieved with the COBE 2991 on Ficoll. Some aspects should be defined, but the preliminary results are undoubtedly of great interest. PMID- 1864551 TI - Prevention of graft-versus-host disease by lymphocyte depletion of the bone marrow graft with use of counterflow centrifugation. AB - A combination of density flotation centrifugation and counterflow centrifugation (elutriation) allows the elimination of 98% of the T-lymphocytes, present in a marrow aspirate. This reduces substantially the occurrence of graft versus host disease (GvHD) after transplantation without loss of the repopulation capacity. A limitation of the traditional Beckman elutriator rotor is the relatively small size of the elutriation chamber, which makes five to six runs, of one hour each, necessary to process the whole bone marrow graft. We developed a new elutriator rotor, containing four disposable elutriator chamber (Dijkstra BV, Amsterdam, The Netherlands), which allows to complete the lymphocyte elimination from the bone marrow graft within 2 hours. Ninety-nine consecutive patients were transplanted with elutriated MLC-negative bone marrow grafts from histocompatible siblings. Indications for transplantation were: AML (n = 32), ALL (n = 34) and CML (n = 33). The grafts contained after counterflow centrifugation a mean of 12.1 (+/- 2.4)% of the nucleated cells, 1.9 (+/- 1.4)% of the T-lymphocytes, and 93.5 (+/- 59.4)% of the CFU-GM, originally present in the collected bone marrow. Immunoprophylaxis post grafting was given to 97 BMT recipients. Primary graft failure occurred in 5 of 95 evaluable patients (5%). The probability of acute GvHD greater than grade 1 at day 100 after BMT was 16%. The projected 3-year estimate of extensive chronic GvHD was 13%. The low incidence of GvHD was associated with a relatively low transplant related mortality in patients above the age of 40 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864552 TI - Immunomagnetic purging procedure for autologous bone marrow transplantation in lymphoid malignancies. AB - In this report we describe the use of the immunomagnetic depletion of tumor cells from harvested bone marrow in two patients with acute lymphoblastic leukemia. The immunomagnetic procedure of purging involved one incubation of the marrow cells with a mixture of 4 monoclonal antibodies which bind to antigens of CD10 (ALB2), CD19 (HD37), CD20 (B1) and CD22 (HD39). Two incubations with magnetic beads (Dynabeads M-450) covered with antimouse antibodies followed by magnetic separation were performed. The bead/target B cell ratio was 50:1. After purging the recovery of mononuclear cells was 56% and 40%, while the recovery of CFU-GM was 45% and 38% respectively. Both patients engrafted rapidly without serious complications. One patient relapsed 4 months after transplant, the other remains in complete remission after 5 months. Our results confirm that the use of immunomagnetic beads is a simple, safe and reproducible technique to remove tumor cells before ABMT in patients with B malignancies using a broad mixture of MoAbs. However only a randomized trial using autologous marrow purged or not will clarify the effective clinical value of the procedure. PMID- 1864554 TI - Juridical and liability reflexes of bone marrow processing. AB - Author analyzes bone marrow processing procedures and points out juridical and forensic-medicine reflexes of this therapeutical act. The aspects of informed consent and professional liability of hematologist are clarified. PMID- 1864553 TI - Detection of bacterial contamination in bone marrow graft. AB - A rapid method of determining bacterial contamination was used in a series of fifty-five bone marrow harvests (20 allogeneic and 35 autologous transplantations). The microbiological culture assays executed on bone marrow samples soon after the harvest and before the manipulation, showed a positivity only in the autologous bone marrow group. Another positivity was revealed after the freezing process of bone marrows for autologous transplantation. Two samples in the bone marrow group submitted to purging were positive after treatment and freezing process. In this study, the increase of bacterial contamination frequency seemed to be related to extensive handlings, such as pharmacological in vitro purging and freezing procedures. PMID- 1864555 TI - Heparin prevents stasis-induced thrombosis through protection of the venous endothelial cells: an electron microscopic study in rabbits. AB - This study was performed to see whether or not protection of the endothelial cells contributes to the antithrombotic effects of heparin. New Zealand albino rabbits were subjected to jugular vein stasis by single caudal ligation for 2 h. Three treatments were given: saline (control group), heparin (0.2 mg/kg) 5 or 45 min before ligature of the vein. Groups of 6-8 animals were killed at 0, 5, 15, 30 and 120 min. The following parameters were determined: (1) involution and damage of the endothelial cells by scanning and transmission electron microscopy; (2) incidence and weight of thrombi in the lumens of the veins after 2 h stasis, and (3) effects of heparin on APTT and anti-Xa activity. In the control group, stasis caused a considerable involution of the endothelial cells in the first 30 min, followed by fibrin deposition and thrombus generation. Heparin strongly reduced the damage to the endothelial cells, with very evident protection of the cell membranes, and prevented thrombus generation: there were significant decreases in both incidence and weight of thrombi. These effects of heparin were evident both shortly after (maximal anticoagulant effect) and long after (no anticoagulant effect) pretreatment. We think that, under the experimental conditions we used, heparin prevented venous thrombosis at least partially by protection of the endothelial cells, through unknown mechanisms. PMID- 1864556 TI - Plasma homocysteine in venous thromboembolism. AB - Severe hyperhomocysteinemia due to inborn errors of methionine metabolism results in precocious development of arteriosclerosis and predisposition to venous and arterial thromboembolism. Although the findings of several studies have indicated that mild hyperhomocysteinemia is common in occlusive arterial disease, no similar studies have been made on venous thromboembolism. In this study of subjects under 50 years of age, we found no significant differences in the plasma homocysteine concentrations, either in the fasting state or after methionine loading, between 42 patients with venous thromboembolism and 42 healthy controls. Nonetheless, male patients manifested a tendency toward higher homocysteine concentrations than male controls; 6 patients (14%) versus 2 controls (5%) responded abnormally to methionine loading which might indicate heterozygosity for cystathionine synthase deficiency. Thus, further studies on plasma homocysteine in venous thromboembolism are warranted. PMID- 1864557 TI - The onset of mammary extraction of plasma triglycerides and circulating levels of progesterone during lactogenesis in the cow and goat. AB - In untreated cows and goats, the onset of mammary extraction of plasma triglyceride was sometimes detected several hours before parturition, prior to removal of secretion from the mammary glands by offspring and when circulating progesterone concentrations were low. In cows and goats that had secretion regularly removed from the mammary glands late in gestation, the onset of triglyceride extraction occurred up to several days before parturition, when circulating progesterone concentrations were moderately high (up to 3.9 ng/ml in the cow and 6.2 ng/ml in the goat). PMID- 1864558 TI - The effect of thymosin fraction 5 on lipid peroxidation in rabbits fed a high cholesterol diet. AB - Plasma and erythrocyte lipid levels and susceptibility of erythrocytes to lipid peroxidation were determined in rabbits fed diet containing 2% (w/w) cholesterol, for 3 months. Hypercholesterolemic rabbits had high plasma and erythrocyte lipid peroxide levels as compared to control rabbits. After high-cholesterol diet, the rabbits in the experimental group were divided into two groups. The first group was fed a normal diet for 21 days and the second group was given normal diet plus thymosin F5 injections every other day for the same period. At the end of this period, plasma and erythrocyte lipid peroxide levels were significantly decreased in the group injected with thymosin F5. PMID- 1864559 TI - Glucose tolerance and incidence of pancreatic islet cell antibodies in pregnancy in women with thyroid autoantibodies. AB - The prevalence of pancreatic islet cell antibodies (ICA) and complement fixing ICA (CF-ICA) and the effect of pregnancy of glucose tolerance was studied in 3 groups of women. One group had thyroid autoantibodies in serum detected in early pregnancy and subsequent development of postpartum thyroiditis (PPT), another group had thyroid autoantibodies without signs of PPT and the third group did not have thyroid autoantibodies or PPT. In the women with thyroid autoantibodies and PPT, ICA were found in one of 12 women (8%, 95% confidence limits 0-38%). In the group with thyroid autoantibodies without PPT, ICA were found in three of 27 women (11%, 2-29%), whereas two of 20 women without thyroid autoantibodies had ICA (10%, 1-32%), N.S. Where present, serum ICA levels were very low and similar in early pregnancy and 6 months postpartum. CF-ICA were only found in two women with thyroid autoantibodies without signs of PPT. In all groups glucose tolerance was impaired in pregnancy when compared to postpartum despite an increased insulin response to glucose ingestion. In pregnancy, however, glucose tolerance was more impaired in the women with thyroid autoantibodies and subsequent PPT, than in the women without thyroid autoantibodies. Postpartum glucose tolerance was similar in all groups. It is concluded, that the presence of thyroid autoantibodies in early pregnancy or development of PPT is not accompanied by an increased prevalence of islet cell antibodies, but women with thyroid autoantibodies and subsequent PPT have a significantly more reduced glucose tolerance in late pregnancy than women without thyroid autoantibodies. PMID- 1864560 TI - Serum bone Gla protein (BGP) during treatment of hyperthyroidism and hypothyroidism. A longitudinal study. AB - Serum bone gamma-carboxyglutamic acid-containing (Gla) protein (BGP) was measured before and with initially 2 weeks, later 4-8 weeks intervals for 20-58 weeks during treatment of patients with hyperthyroidism (n = 10) and hypothyroidism (n = 4). Biochemical euthyroidism was obtained in the hyperthyroid patients after a median of 3 weeks (range 1-8 weeks), and in the hypothyroid patients after a median of 17 weeks (range 10-27 weeks). Serum BGP levels closely followed the thyroid state, being high respectively low in the hyperthyroid and hypothyroid state and reaching a stable plateau just at the time biochemical euthyroidism was obtained. These data suggest that osteoblastic activity is enhanced in hyperthyroidism and reduced in hypothyroidism, and that normalization occurs in close conjunction with the normalization of the thyroid state, without any delay, indicating a direct effect on the function of the excisting osteoblasts by the thyroid hormones. PMID- 1864561 TI - Glycolipids and complete Freund's adjuvant cause insulitis in rats. PMID- 1864562 TI - Plasma prolactin and insulin changes on feeding leucine supplemented diet in rats. PMID- 1864564 TI - Remembering mental hospitals through the prism of time. PMID- 1864563 TI - Triiodothyronine antibodies in a case of Graves' disease: long-term follow-up under carbimazole. PMID- 1864565 TI - Community psychiatry's changing role. PMID- 1864566 TI - Perspectives on human functioning. PMID- 1864567 TI - Violence by psychiatric inpatients: a review. AB - The literature on violence by psychiatric inpatients provides some evidence that rates of violence may be increasing over time and that they are higher in the United States than in other nations. This review examines the extent of inpatient violence and describes the individual, situational, and structural factors with which it is associated. Individual factors include acute illness, psychosis, drug abuse, age, and history of violence. Situational variables include overcrowding, provocation, staff inexperience, and management tolerance of violence. Structural factors include changes in mental health policy that have made dangerousness a frequent criterion for commitment and a shortage of treatment resources. The author concludes that violence is the result of an interaction between the various types of factors and is not simply an expression of individual pathology. PMID- 1864568 TI - A personal memoir of the state hospitals of the 1950s. AB - The author recalls his experiences as an attendant at a state mental hospital in the early 1950s, before the introduction of psychotropic drugs. State hospitals of that era served not only as treatment centers for mentally ill patients but also as de facto nursing homes, retirement homes, orphanages, and shelters for chronic physically ill persons, medically ill poor people and wards of the state, adults and juveniles convicted of crimes, behaviorally disturbed retarded people, and alcoholics. The author argues that the deinstitutionalization movement removed an important, if unrecognized, source of palliative care for dispossessed individuals and recommends redesigning the state hospital to provide compassionate housing and treatment by trained persons for homeless and chronic physically and mentally ill individuals. Four patients typical of the heterogenous population of state hospitals in the 1950s are described. PMID- 1864569 TI - Treatment protocols in child and adolescent day treatment. AB - Twenty treatment protocols in a day treatment program for children and adolescents have been developed by multidisciplinary groups based on a review of 200 patients. The protocols classify patients according to symptom clusters and provide standardized treatment plans for each classification. Each protocol contains a definition of the symptom cluster, a list of presenting problems, a list of other protocols to consider, admission guidelines, treatment options, and discharge criteria. The authors describe the developmental process for the protocols and present a clinical case example to illustrate their use. The application of treatment protocols in research, quality assurance, and teaching is briefly discussed. PMID- 1864570 TI - Clinical skills for the 1990s: six lessons from HMO practice. AB - Clinical practice in health maintenance organizations (HMOs) currently has many of the features that will become increasingly common in the managed-care environment in which mental health treatment will be provided in the 1990s. HMO policies calling for cost containment, attention to outcomes, practice audits, and treatment guidelines create distinctive demands on clinicians regarding their focus of attention, clinical stance, and professional role. The author identifies six crucial skills that can help clinicians meet these demands effectively: population-oriented practice management, population-oriented program development, ability to apply an adult developmental model, command of a broad repertoire of methodologies, ethical analysis, and advocacy. He uses brief case examples to illustrate how these skills may be used in managed-care settings. PMID- 1864571 TI - Treatment cost and rehospitalization rate in schizophrenic outpatients with a history of substance abuse. AB - Retrospective self-report data from 60 chronic schizophrenic outpatients in a community support program (CSP) were used to study the relationship between a history of substance abuse and rate of psychiatric rehospitalization and outpatient treatment cost. The sample showed a significant overall reduction in days spent in a psychiatric hospital or jail and in outpatient treatment expenses during the first year in the CSP. Although subjects with recent symptoms of substance abuse (N = 27) showed consistently smaller reductions than subjects with no history of substance abuse (N = 17) or subjects with no recent substance abuse symptoms (N = 16), the only significant difference between the groups was in the total number of days spent in an institution. However, the findings suggest that treatment of patients with concurrent substance abuse and schizophrenia is disproportionately more costly than that of patients without dual diagnoses. PMID- 1864572 TI - Characteristics of patients attending an HIV-related psychiatric clinic. AB - Demographic and clinical data were recorded for 324 patients who visited an AIDS related psychiatric outpatient clinic over a three-year period. Seventy-five percent of the patients had a diagnosis of AIDS, AIDS-related complex, or asymptomatic HIV seropositivity. Intravenous drug use and heterosexual relations were the most common HIV transmission risk factors. Seventy-three percent of the patients were black or Hispanic; 51 percent were female. In all stages of HIV infection, adjustment disorder was the most common diagnosis; one third to one half of the patients had substance abuse diagnoses. Only 5 percent were diagnosed with dementia, with the incidence highest (12 percent) in patients with AIDS. On the basis of their experience with the clinic, the authors discuss issues that have proved important in the treatment of patients with the triple diagnoses of medical illness, mental illness, and substance abuse. PMID- 1864573 TI - Inpatient psychiatric morbidity of HIV-infected soldiers. AB - To determine differences in inpatient psychiatric morbidity, a total of 573 soldiers seropositive for the human immunodeficiency virus (HIV) were matched with 2,266 seronegative soldiers by age, sex, race, marital status, military rank, length of active service, military occupation, and date of HIV test. An HIV infected individual was seven times more likely to be hospitalized than an uninfected individual. The rate of total hospitalizations was 16 times higher for the HIV-infected soldiers. The median length of hospital stay was six days for the infected soldiers and four days for the control group. The incidence of psychosis, organic mental disorders, and adjustment disorder in the HIV-infected group was significantly higher. PMID- 1864574 TI - Responses of mental health professionals to lay-offs. AB - In this study, 39 laid-off mental health professionals responded to a questionnaire that focused on the emotional stress of being laid off and the respondents' efforts to cope with the stress. In the early weeks after lay-off, shock, disbelief, anger, and sadness gave way to depression, anxiety, and feelings of being betrayed and discounted. Most respondents coped with these feelings by talking to others who were being laid off or by focusing their energies on seeking a new job. Many respondents felt that mismanagement of the lay-off process was a major factor in their emotional distress. The author makes recommendations for managing lay-offs based on the responses of the laid-off workers and the principles of crisis management. She also speculates about why most of the lay-offs were poorly managed. PMID- 1864575 TI - One-year follow-up of 24 patients in a clinical trial of clozapine. PMID- 1864576 TI - Patient self-regulation and functioning in schizophrenia. PMID- 1864577 TI - Seven-year follow-up of an adolescent volunteer program in a psychiatric hospital. PMID- 1864578 TI - Preference for hospital-based outpatient treatment among Japanese patients in Vancouver. PMID- 1864579 TI - Smoking patterns among patients discharged from a smoke-free inpatient unit. PMID- 1864580 TI - Benefits of inpatient care. PMID- 1864581 TI - TV and ECT. PMID- 1864582 TI - Telepathology comes of age in Norway. PMID- 1864583 TI - Remote frozen section service: a telepathology project in northern Norway. AB - We discuss the organization of a remote frozen section service in northern Norway. The service is operated by remote control of a motorized video-microscope located at Kirkenes Hospital, at a distance of more than 400 km from the workstation at the University Hospital in Tromso. The video images of the frozen section are transmitted via a two-way telephone and video telenetwork with a 2 Mbit/s capacity. The images are displayed on monitors and diagnosed by pathologists in Tromso. To date, 17 patients have been examined by remote frozen section. Correct benign versus malignant diagnoses have been given in all 17 cases compared with final diagnoses based on formalin-fixed and paraffin-embedded material. The average time taken for examining each frozen section was 15 minutes (range, 5 to 30 minutes). In none of the cases was the interpretation of the slides difficult due to deficient quality of the video images. For small hospitals with limited availability of local pathology services and for hospitals with a deficiency of specialists, telepathology may be a worthwhile substitute. PMID- 1864584 TI - Familial amyloidotic polyneuropathy type 1 in Kumamoto, Japan: a clinicopathologic, histochemical, immunohistochemical, and ultrastructural study. AB - Seventeen autopsy and five biopsy cases of familial amyloidotic polyneuropathy were examined clinicopathologically, histochemically, immunohistochemically, and ultrastructurally. In the autopsy cases, amyloid deposits were predominant in the peripheral nerve tissues, autonomic nervous system, choroid plexus, cardiovascular system, and kidneys. Amyloid involvements in the anterior and posterior roots of the spinal cord, spinal ganglia, thyroid, and gastrointestinal tract were also frequent. In the cardiac conduction system, amyloid deposition was prominent in the sinoatrial node and in limbs of the intraventricular bundle. In the sural nerve biopsy, besides amyloid deposits, degenerative changes of nerve fibers and Schwann cells were detected ultrastructurally, and the morphometric analysis showed a marked reduction in the number of myelinated fibers which correlated with the clinical stage. Amyloid deposits were resistant to pretreatment with potassium permanganate in Congo red staining, and transthyretin was confirmed immunohistochemically as a major component of amyloid deposits, along with the presence of serum amyloid P-component. Besides the amyloid deposits, transthyretin was proven in the liver cells, epithelial cells of the choroid plexus, and pancreatic islet A cells, suggesting that the transthyretin produced by these cells is secreted, transferred into tissues, and deposited in situ as the major component of amyloid in this disorder. PMID- 1864585 TI - Bronchocentric injury in Wegener's granulomatosis: a report of five cases. AB - While Wegener's granulomatosis is recognized primarily for its vascular destruction, the extravascular granuloma is an integral part of the inflammatory process. We report five illustrative cases of this phenomenon in which the necrotizing process appeared to be centered primarily on the airways. This was associated with multisystem disease and cavitary lung nodules, which probably resulted from extensive airway necrosis. Prognosis with conventional cytoxan and prednisone therapy was excellent. The differential diagnosis of bronchocentric Wegener's granulomatosis with bronchocentric granulomatosis, infection, and aspiration pneumonia is discussed. PMID- 1864586 TI - Senile scleral plaques: a histopathologic study using energy-dispersive x-ray microanalysis. AB - The investigators reviewed the pathologic findings of 21 senile scleral plaques in 17 enucleated globes. Eyes were fixed in formalin and routinely processed for light microscopic examination. Two representative calcified scleral plaques were subjected to energy-dispersive x-ray microanalysis. Plaques were located in the sclera just anterior to the insertion of the horizontal rectus muscles. Microscopic examination of the involved sclera disclosed a spectrum of histopathologic changes involving increased hematoxylinophilia of the scleral collagen, decreased stromal cellularity, the presence of scleral fibers with a unique corkscrew appearance, and calcium deposition. The calcified plaques contained calcium phosphate as indicated by histochemical methods and energy dispersive x-ray microanalysis. Conjunctival elastosis was present in 12 of the 14 eyes in which sufficient conjunctiva was present for histologic evaluation. Accumulated actinic damage from solar irradiation may play a role in the pathogenesis of senile scleral plaques. PMID- 1864587 TI - Leiomyosarcoma of somatic soft tissues in childhood: an immunohistochemical analysis of six cases with ultrastructural correlation. AB - Leiomyosarcoma (LMS) of soft tissue is a rare tumor in children. Although LMS may exhibit clinical and histologic features that are typical of smooth muscle neoplasms in adults, they may often be confused with or resemble tumors of presumed fibroblastic, myofibroblastic, or rhabdomyoblastic differentiation. As a result, the diagnosis of LMS in children is often difficult to establish with confidence. To address this problem, we analyzed the immunohistochemical features of six LMS in children (one of deep soft tissue of an extremity, one of paravertebral tissue, one of the retroperitoneum, two of oropharyngeal soft tissue, and one of subcutis); the ultrastructural features of four of these tumors were also studied. Histologically, each of the three tumors of deep soft tissue and one of the retromolar trigone were composed of pleomorphic spindle cells arranged in interweaving fascicles. In contrast, the subcutaneous tumor and the lesion of the hard palate had an epithelioid appearance. Ultrastructural features were typical of adult type LMS. Immunohistochemically, these neoplasms were diffusely reactive for vimentin, while each was negative for cytokeratin, epithelial membrane antigen, and S-100 protein. Desmin was present in all cases, but was expressed only focally in three; a similar pattern of staining was noted for muscle-specific actin, although staining was generally noted in a larger population of cells. alpha-1-Antichymotrypsin was found in five tumors, and cathepsin B reactivity was encountered in four cases. Leu-7 antigen and myelin basic protein were coexpressed by one tumor, but neither was found in the remaining cases. These results indicate that immunohistochemical detection of desmin and muscle-specific actin may be useful in the differential diagnosis of spindle or epithelioid cell proliferations in childhood when ultrastructural analysis in unavailable. PMID- 1864588 TI - Immunophenotypic heterogeneity in osteosarcomas. AB - Eighteen osteosarcomas were studied immunohistochemically. The tumors were classified into the following six histologic subtypes: five osteoblastic, four chondroblastic, four malignant fibrous histiocytoma-like, two telangiectatic, two low-grade central, and one giant cell-rich. Variable amounts of osteocalcin immunoreactivity were found in all tumors. Factor XIIIa-positive cells, which may be of fibrohistiocytic lineage, were present in three tumors of the malignant fibrous histiocytoma-like type, one of the telangiectatic type, one of the low grade central type, and the tumor of the giant cell-rich type. One tumor of the osteoblastic type showed cytokeratin and epithelial membrane antigen immunoreactivities. The positive reactions for desmin in four tumors, for alpha smooth muscle actin in 11 tumors, and for type IV collagen in one tumor seemed to indicate myofibroblastic differentiation of some tumor cells. S-100 protein positive tumor cells were detected not only in all four tumors of the chondroblastic type, but also in three of the osteoblastic type, one of the low grade central type, and in the tumor of the giant cell-rich type. These immunohistochemical results suggest that osteosarcomas are composed of heterogeneous cell populations, such as those of the osteoblastic, chondroblastic, myofibroblastic, and fibrohistiocytic types, and occasionally also of cells with epithelial features. PMID- 1864589 TI - Placentomegaly with massive hydrops of placental stem villi, diploid DNA content, and fetal omphaloceles: possible association with Beckwith-Wiedemann syndrome. AB - Marked placental hydrops is generally associated with hydatidiform mole. Diagnosis of hydatidiform mole requires both villous hydrops and trophoblast hyperplasia. This report describes four cases with massive hydrops of placental stem villi without associated trophoblast hyperplasia. All four had diploid DNA content by flow cytometry. Fetal omphalocele was present in three; and one had diagnostic Beckwith-Wiedemann syndrome (BWS). In two others, there were pathologic features suggestive of BWS. The fourth fetus had multiple anomalies by ultrasound; autopsy examination of the fragmented fetus failed to disclose additional pathology. The association of massive placental hydrops involving stem villi, fetal omphalocele, and diploid DNA content is unusual. These fetal and placental findings may suggest possible BWS in some cases and allow for antenatal diagnosis of affected fetuses, clinical evaluation of additional family members, and planning for neonatal care. PMID- 1864590 TI - The value of monoclonal antibody B72.3 for the diagnosis of breast carcinoma: experience with the first commercially available source. AB - One hundred cases of invasive breast carcinoma were studied using the commercially available monoclonal antibody Anti-Human Tumor-Associated Glycoprotein-72 (MAb B72.3, Biomedical Technologies Inc, Stoughton, MA) prediluted at 8.5 micrograms/mL. Forty-three cases displayed positive reactivity with this antibody. Intensity and distribution of positive staining varied among the tumor cells. Twenty-two cases had 1% or less reactive cells, while eight cases contained 40% or more positive tumor cells. Apical cell membrane and diffuse cytoplasmic staining were present. In fifteen cases intracytoplasmic lumina and extra-cellular secretory material were highlighted by positive staining. Thirty-five cases had benign breast tissue adjacent to the tumor. Benign ductal and lobular epithelial cells were nonreactive except for two cases in which small foci of apocrine metaplasia were positive. Reactivity with MAb B72.3 was not dependent upon histologic grade, nuclear grade, nodal status, or patient age. Excluding the lower number of positively stained cases, our findings were similar to other MAb B72.3 investigations. The number of positively stained cases and the intensity of the positivity were increased by using MAb B72.3 at 5.0 micrograms/mL with overnight incubation, or by using MAb B72.3 at 40.0 micrograms/mL with 2 hours of incubation. Our findings confirm that MAb B72.3 shows reliable reactivity with breast carcinoma that is sensitive to antibody concentration and incubation time without loss of specificity for tumor cells. Our results are also consistent with the view that MAb B72.3 probably detects epithelial membrane-related antigens in breast carcinoma, as do several other antibodies. PMID- 1864591 TI - The internal carotid artery siphon in children and adolescents. AB - We observed significant lesions of the carotid artery siphon in two young subjects with fatal stroke. Because stroke in children and adolescents is uncommon and poorly understood, we examined the internal carotid artery in the 'siphon' of the skull in 24 unselected, but nearly consecutive autopsies. The age range was 10 days to 38 years, with 11 males and 13 females, six blacks, and 18 whites. In no case was stroke the cause of death. Intimal lesions of two types were found in the carotid siphon of all cases. (1) The first was focal splitting and/or duplication of the internal elastic lamina with variable proliferation of smooth muscle. The resulting 'fibrous' plaques or cushions, when severe, were usually found at natural bends in the artery. The number and severity of this type of lesion increased with age, but there were no differences in severity or distribution when compared by sex, race, or mode of death. (2) The second was internal elastic calcification which was found in all cases older than 9. This was increasingly severe with age. Although the frequency of the vascular lesions was surprisingly high, the relationship of either type to dissecting aneurysm or other stroke lesion remains unclear. PMID- 1864592 TI - Hepatic fibrin-ring granulomas: a clinicopathologic study of 23 patients. AB - Twenty-three patients with characteristic hepatic fibrin-ring granulomas were studied. Q fever accounted for 10 cases (43%), visceral leishmaniasis for five cases (22%), boutonneuse fever for two cases (9%), and toxoplasmosis, Hodgkin's disease, and allopurinol hypersensitivity for one case each (4%). The etiology remained undetermined in three cases (13%). This report broadens the range of etiologies of hepatic fibrin-ring granulomas to include boutonneuse fever and toxoplasmosis in the differential diagnosis of ring granulomas, and it could serve as a guideline to the clinician and pathologist for the most frequent categories of disease associated with this morphologic pattern. PMID- 1864593 TI - Adenocarcinoma and (extragonadal) choriocarcinoma of the gallbladder in a young woman. AB - This study represents the second case of coexisting adenocarcinoma and choriocarcinoma of the gallbladder reported in the English language medical literature, and the first such case documented by: (1) positive immunostaining of tumor cells for the beta subunit of human chorionic gonadotrophin, and (2) evidence of gonadotrophin secretion in blood and urine. The patient reported herein survived only 1 month following diagnosis, and exemplifies the reportedly lethal behavior of extragonadal choriocarcinoma. PMID- 1864594 TI - Crisis in sickle cell trait. AB - A 34-year-old black male with hemoglobin AS was admitted for renal failure, polydipsia, hypertension, schizophrenia, mental confusion, and visual hallucinations. Abnormal electrolytes were corrected by dialysis, but blood specimens were reported as hemolyzed with hyperkalemia. Peaked T waves on electrocardiographic analysis were followed by cardiac arrest. An autopsy revealed sickled cells in the visual cortex and other symptomatic organs, but normal erythrocytes in most of the vascular tree. These findings suggest true progressive sickle cell crisis in a hemoglobin AS patient. PMID- 1864595 TI - Osteoclast-like giant cell tumor of the pancreas: immunophenotypic similarity to giant cell tumor of bone. AB - An immunophenotype was performed on an osteoclast-like giant cell tumor of the pancreas using a panel of antibodies to epithelial and leukocyte antigens. Several antibodies to cytokeratin and carcinoembryonic antigen were negative in the tumor. Osteoclast-like cells were positive for CD4, CD13, CD45, CD68, CD71, and vimentin, but negative for lysozyme and HLA-DR. Mononuclear tumor cells were positive for CD4, CD11c, CD13, CD14, CD45, CD68, CD71, HLA-DR, and vimentin, but negative for lysozyme. The phenotype is similar to that previously described for giant cell tumor of bone. The osteoclast-like cell phenotype is also similar to that reported for normal osteoclasts. The findings support a nonepithelial origin for osteoclast-like giant cell tumor of the pancreas, and suggest a derivation similar to giant cell tumor of bone. PMID- 1864596 TI - Chlamydia trachomatis in chronic abacterial prostatitis. PMID- 1864597 TI - Prospects for homologous recombination in human gene therapy. AB - The ideal approach to gene therapy of hereditary diseases or gene correction therapy is considered. The advantages, disadvantages and limits of gene targeting by homologous recombination are discussed with regard to its possible application in gene correction therapy and in comparison with retroviral-mediated gene complementation therapy. PMID- 1864598 TI - Induction of distamycin A-inducible rare fragile sites and increased sister chromatid exchanges at the fragile site. AB - Expression of distamycin A-inducible rare fragile sites by AT-specific DNA ligands was examined in lymphoblastoid cell lines derived from heterozygous carriers for the fra(8)(q24), fra(16)(p12), and fra(16)(q22) sites. The sensitivity of fragile site expression to the inducers was different at these fragile sites. The expression of fra(8)(q24) was induced markedly by Hoechst 33258, but not by distamycin A or berenil. An increased expression of fra(16)(p12) was found following treatment with Hoechst 33258 or berenil, but not with distamycin A. At fra(16)(q22), distamycin A markedly induced the fragile site, but Hoechst 33258 and berenil did not. Since their response to the different inducers was similar to that found in cultured lymphocytes, lymphoblastoid cell lines appear to retain their inherent properties. Although BrdUrd alone did not induce any fragile sites, concomitant treatment with BrdUrd plus the inducer was synergistically effective in inducing all the fragile sites. An increased frequency of sister chromatid exchanges was observed at fra(16)(p12) following simultaneous treatment with BrdUrd and berenil, mainly when the site was expressed as an isochromatid gap. Thus, the induced fra(16)(p12) site is a hot spot for the formation of sister chromatid exchanges, as found in other reported fragile sites. PMID- 1864599 TI - Non-isotopic detection of chromosome 1 in human meiosis and demonstration of disomic sperm nuclei. AB - Nonradioactive in situ hybridization with the biotin-labeled chromosome 1 specific probe pUC1.77 was performed on human mitotic and meiotic chromosomes, and on sperm nuclei. The streptavidine-horseradish-peroxidase and diaminobenzidine detection system demonstrated heteromorphisms in the 1q12 heterochromatic region, not only in mitotic cells but also in mature sperm heads. The localization of chromosome 1 could be traced through all meiotic stages and in the sperm nuclei. The frequency of chromosome 1 disomy in human sperm, as indicated by two distinct hybridization signals, was calculated to be 0.41%. PMID- 1864600 TI - High prevalence of aspartylglycosaminuria among school-age children in eastern Finland. AB - A high prevalence of the lysosomal storage disease aspartylglycosaminuria was found in a study of four birth cohorts of 12882 children in eastern Finland. Using school achievement tests and registers of mentally retarded individuals, 178 mentally retarded children were identified. Randomized urine samples from 151 of the 178 retarded children and from 101 healthy children were analyzed quantitatively for aspartylglucosamine by high-performance liquid chromatography. The results identified three affected individuals in the retarded group indicating an exceptionally high prevalence of aspartylglycosaminuria (1:3643) in the study population, consistent with a carrier frequency of 1:30. The 95% confidence limits for the prevalence are 1:4 352-1:16389. This is the highest prevalence described for any glycoproteinosis in any population and comparable to the incidence figures of the most common lysosomal storage diseases, Gaucher disease type I and Tay-Sachs disease among Ashkenazi Jews. In the study group, aspartylglycosaminuria was, after trisomy 21 (n = 19) and the fragile X syndrome (n = 6), the most common genetic cause for mental retardation. PMID- 1864601 TI - The murine Rb(6.16) translocation: evidence for sperm selection and a modulating effect of aging. AB - The segregation products of the Rb(6.16) translocation were studied at first cleavage metaphase. Male mice heterozygous for the translocation mated at 3- and 14-day intervals to superovulated random-bred ICR females. Chromosome preparations of the recovered one-cell embryos were sequentially G- and C-banded and male and female complements analyzed cytogenetically. Of the 309 zygotes analyzed from both mating groups, no unbalanced segregants of the translocation were observed. In the 3-day group there was a highly significant difference (P less than 0.001) from the expected 1:1 ratio between sperm with normal (70.5%) and balanced segregants (26.2%) of alternate segregation. In the 14-day group the level of significance for the difference was ten times lower (P less than 0.01) as normal segregants were observed in 56.4% of the sperm and balanced ones in 36.5%. A comparison of the two groups using a 2 x 2 contingency table showed that segregant type was related to mating frequency (P less than 0.05). There was a highly significant distortion (P less than 0.01) of the sex ratio, with 178 Y bearing and 131 X-bearing sperm in the combined populations. When sex ratio was analyzed according to mating intervals, the distortion was significant (P less than 0.01) only for the 3-day group. An analysis of the sex ratio according to the segregant type showed no significant deviation from 1:1 for type 1 segregants, which had normal chromosomes, while type 2 segregants, with the translocation, had a deficiency of X-bearing sperm. This deficiency was significant (P less than 0.05) only for the 3-day population. Analysis of meiotic preparations showed no association between the translocation trivalent and the X Y bivalent. Our results, obtained under physiological conditions, provide definitive evidence for sperm selection and support previous findings that aging of sperm can modify the effect of selection. PMID- 1864602 TI - Cytogenetic investigations in three cell types of a Saudi family with ataxia telangiectasia. AB - Chromosomal analyses were performed on lymphocytes, fibroblasts and lymphoblastoid cell lines derived from a Saudi family with ataxia telangiectasia (AT). The three siblings of a consanguineous marriage were all affected. The lymphocytes of the AT homozygotes (probands) showed an increase of 2- to 6-fold and 4- to 8-fold respectively, in the frequency of spontaneous and X-ray-induced chromosomal aberrations compared with controls, while the parents (obligate heterozygotes) of the patients showed no notable difference. The unirradiated lymphocytes from the oldest AT sibling, an 11-year-old boy (AT1), showed specific rearrangements involving chromosomes 7 and 14 [t(7;14)(q35;q12)] and 12 and 14 [t(12;14)(q23;q12)] in two different clones. The most severely affected sibling was a 9-year-old girl (AT2) who presented with a clone showing a novel rearrangement involving chromosomes 14 and 17, namely: del(14) (q31q32) and dup(17)(q21-q24). The lymphocytes from the third sibling, a 2-year-old boy (AT3), showed a t(2;14)(p24;q12). In addition, an inv(14)(q12q32) was observed in all three AT patients, while inv(7)(p14q35) was found only in patients 2 and 3. The lymphocytes from the AT parents and controls showed normal karyotypes. The breakpoints involving chromosomes 2, 12 and 17, observed in our studies, have rarely been reported in other series of AT patients. No non-random chromosomal rearrangements were observed either in the skin fibroblasts or in the lymphoblastoid cell lines derived from the AT patients, although all cell lines showed an increase in both spontaneous and radiation-induced chromosomal breaks per cell. The present study constitutes the first report on a cytogenetic analysis of a Saudi family with three AT siblings. PMID- 1864603 TI - Characterization of seven DA/DAPI-positive bisatellited marker chromosomes by in situ hybridization. AB - Seven dicentric bisatellited marker chromosomes, ascertained at amniocentesis, chorionic villus sampling, and in blood from an abnormal liveborn were characterized cytogenetically. All seven markers demonstrated brilliant bands by the DA/DAPI technique corresponding to C-band positive regions. Although some dicentric DA/DAPI-positive bisatellited markers have been identified as inverted duplicated 15s, recent literature has suggested that DA/DAPI lacks specificity for chromosome 15. Our evaluation of DA/DAPI-positive bisatellited marker chromosomes by in situ hybridization shows that some originate from chromosome 15 whereas DA/DAPI negative bisatellited markers may not be derived from 15. The morphological variations noted in our studies are discussed with respect to nomenclature. PMID- 1864604 TI - Dominant mutations in familial lethal and severe osteogenesis imperfecta. AB - Four families presenting with familial osteogenesis imperfecta (OI) have been studied: 2 with the lethal type II and 2 with the severe type III form. Fibroblasts of the patients, all issue from non-consanguineous parents, produced normal and abnormal alpha(I) chains. These heterozygous mutations differentiate the recurrent forms from homozygous mutations characteristic of autosomal recessive forms. Although the identity of the mutations could not be determined, such recurrence of autosomal dominant OI is probably the result of germinal mosaicism in one of the parents. Biochemical results were consistent with a somatic mosaicism in the father's fibroblasts in one family. Moreover, our studies show that not only OI type II but also severe OI type III can arise from gonadal mosaicism. We discuss the importance of such a phenomenon for genetic counseling. PMID- 1864605 TI - Sister chromatid exchanges are preferentially induced at expressed and nonexpressed common fragile sites. AB - To investigate the relationship between common fragile sites and sister chromatid exchange (SCE), lymphocyte cultures were treated with aphidicolin and bromodeoxyuridine (BrdU) and analyzed using a sequential G----SCE staining protocol. A total of 1,163 SCEs were mapped to their corresponding G-band sites, which were assigned to one of the following four categories: fragile sites expressed; fragile sites nonexpressed; nonfragile sites with breaks; or nonfragile sites with no breaks. The designated common fragile sites were found to be preferred locations for SCE formation, not only when these sites were "expressed" as visible gaps or breaks, but even when they were "nonexpressed" in the cell. SCEs were also more likely to occur at nonfragile sites with breaks than at nonfragile with no break sites. Further, SCEs were found to be distributed nonrandomly across fragile sites and nonfragile sites, and among the fragile sites, the high frequency SCE sites were highly correlated with the high frequency breakage sites. These data support the hypothesis of common steps in the mechanism of aphidicolin-induced SCE formation and common fragile site expression. PMID- 1864606 TI - Recurrent ctb(7)(q31.3) and possible laminin involvement in a neonatal cutis laxa with a Marfan phenotype. AB - A 6-week-old girl presented with cutis laxa, emphysema, heart anomalies and a diaphragmatic hernia. She died at 22 weeks. A recurrent ctb(7)(q31.3) was found and the laminin gene was suspected to be involved in the disease. Anti-human laminin antiserum showed that this protein was absent from the skin. This case, together with 17 other similar cases, could represent a new type of connective tissue disease. PMID- 1864607 TI - Inherited ring chromosomes: an analysis of published cases. AB - A review of case reports on patients with ring chromosome revealed 30 individuals (plus two fetuses) who inherited the ring from a total of 23 carrier parents (21 mothers and 2 fathers). The proportion of cases with inherited rings, among all patients with a ring, was calculated to be 5.6% as an upper limit. However, because of a propable difference in survival and fertility between individuals with transmitted and do novo rings, and because of the preferential publication of cases involving inherited rings (and thus a publication bias), the proportion of inherited rings should in reality be no more than 1%. Out of 30 transmitted rings, there were 9 where parent and child were both mosaics, suggesting an inherited instability of the chromosome involved leading to de novo re-formation of the ring in the second generation. The relatively mild clinical manifestations of ring chromosomes, in general, was found to be even more striking in familial cases. In half of the offspring the phenotype was very similar to that of the parent. However, in about a third of cases the offspring were more severely (mentally) affected. This fact should be considered in genetic counseling of clinically normal women who carry a ring chromosome. PMID- 1864608 TI - Three unique base pair changes in a family with Gaucher disease. AB - Single-stranded cDNA was prepared from RNA obtained from a patient with type 1 Gaucher disease. The cDNA was amplified in vitro and analyzed by sequencing. Three base-pair changes were identified which included a G to C transversion at nucleotide 3119 of the active gene (Asp140----His), an A to C transversion at nucleotide 3170 (Lys157----Gln) and a G to A change at nucleotide 5309 (Glu326--- Lys). To study the mode of inheritance of the three different base-pair changes, genomic DNA was prepared from blood or skin fibroblasts of several family members. Genomic glucocerebrosidase DNA sequences were amplified and subjected to hybridization with allele-specific oligonucleotides (ASOs). The hybridization profiles demonstrated that two of the base-pair changes originated from the mother and were transmitted to her two affected sons and to a grandchild, while the third base-pair change, originating from the father, was transmitted to his two affected sons, a carrier daughter and a second grandchild. Tests of other patients with Gaucher disease failed to disclose the presence of the three base changes. This is a unique family with three base-pair changes tightly linked to Gaucher disease. PMID- 1864609 TI - T296----M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection. AB - By direct genomic sequencing, we have delineated the causative mutation in 64 families of European decent with hemophilia B. Six (9%) had a C----T transition at base 31008, which substitutes methionine for threonine 296 (T296----M) in the catalytic domain of factor IX. Five of the patients had the same haplotype (frequency of 16% in the northern European population). These individuals are of Amish/German descent and they are likely to share a common ancestor. The sixth patient had a different haplotype, which indicates that his mutation had an independent origin. The data highlight the importance of clinical criteria for the classification of hemophilia B. All six patients had clinically mild disease and their factor IX coagulant activities were in the range of 3%-6% when tested simultaneously in one laboratory, yet the factor IX activities provided with patient records varied 40-fold. Due to the high frequency of this mutation, we have utilized the technique of polymerase chain reaction amplification of specific alleles (PASA) to perform rapid and inexpensive carrier diagnoses in the families with this mutation. This is of particular importance for the Amish since the mutation should account for much of, if not all, the mild hemophilia B that is commonly found in this population. PMID- 1864610 TI - X-linked anhidrotic ectodermal dysplasia and de novo t(X;1) in a female. AB - A de novo translocation (X;1)(q13.1;p36.33) was found in a 2-year-old girl with typical clinical features of X-linked anhidrotic ectodermal dysplasia (EDA). The breakpoint at Xq13.1 is approximately the same as has been described in 2 other EDA females with X;autosome translocations. PMID- 1864611 TI - Increased band sharing in DNA fingerprints of an inbred human population. AB - We have compared band sharing between the DNA fingerprints of members of an inbred human population with band sharing between members of an outbred population. It had not previously been determined whether the high rate of mutation at minisatellite loci is sufficient to prevent an increase in band sharing in moderately inbred populations. We have found that there is an increase in band sharing in the 2-kb to 9-kb size range, but not in the greater than 9-kb size range, in the inbred population. The difference was consistently observed using four different multi-locus probes, viz. 33.6, 33.15, (CAC)5 and M13. Thus, we have demonstrated that moderate but prolonged inbreeding can lead to increased similarity in human DNA fingerprints. This should be considered when analysing DNA fingerprints in forensic or paternity cases involving members of an inbred community. PMID- 1864612 TI - Genotype-phenotype correlation and germline mosaicism in DMD/BMD patients with deletions of the dystrophin gene. AB - The molecular analysis of 127 DMD/BMD patients showed that 73 of them (57%) had deletions in the dystrophin gene. Two different methods were used in this study: (a) hybridization of HindIII-digested genomic DNA with nine cDNA probes corresponding to the entire 14kb cDNA of the DMD gene; and (b) simultaneous amplification of nine exons of the DMD gene (multiplex DNA amplification) by the polymerase chain reaction (PCR). When the deletion breakpoints of the intragenic deletions were analyzed with regard to their phenotypic consequences, nine patients were found to represent exceptions to the reading-frame hypothesis. Information regarding mental development was also available for 61 of the 73 deleted patients and for 34 of the 54 non-deleted ones. The proportion of mentally retarded patients was found to be similar in the two groups (deleted, 15%; non-deleted, 18%). Finally, in one family, a junction fragment present in the patient was not found in the peripheral blood DNA of the mother but was present in the sister, thus indicating germline mosaicism in the mother. PMID- 1864613 TI - Isatin--a new biological factor. PMID- 1864614 TI - Isonicotinic acid hydrazide inhibits cell population growth during teratogenesis of chick embryo. AB - In chick embryos treated with a 4 hr pulse of 7.2 X 10(-5) M isonicotinic acid hydrazide (INH) the cell population growth is inhibited with an increased population doubling time. Teratogenised blastoderm cells complete their ongoing cell cycle and arrest in G1 phase. A chase with an equimolar concentration of pyridoxal-5-phosphate restores the growth rate after a lag of 4 hr equivalent to the duration of treatment with INH. Presumptive mesoblast cells invaginated through the primitive streak and neuroectoblast cells induced prior to the application of INH differentiate, while the teratogen inhibits morphogenesis and organization of organ primordia. PMID- 1864615 TI - Decidual cell reaction: relative response to traumatization in uterus of rat, hamster and guinea pig. AB - Relative decidual cell response to traumatization was studied in the uterus of immature rat, hamster and guinea pig. A single dose of progesterone (1.0 mg/animal) caused 285 +/- 41 and 459 +/- 58% uterotrophy in traumatized horn of rat and hamster respectively, while in guinea pig increasing doses of progesterone (1, 2 and 5 mg/animal), several combinations of estrogen and progesterone or alteration in treatment schedule of the two hormones as well as extending the day of traumatization failed to elicit comparable uterotrophic response. Uterus of immature hamster was found to be most responsive to traumatization and that of guinea pig the least. PMID- 1864616 TI - Intra-and interchromosomal effects of heterozygous inversions on recombination in the third chromosome of Drosophila ananassae. AB - In order to study intra-and interchromosomal effects of heterozygous inversions on recombination in the third chromosome of D.ananassae, experiments were conducted using Stw-pr marker stock and five wild stocks with known karyotypes. The stocks used were homozygous for standard or inverted gene sequence in 2L, 3L, and 3R. Recombination was investigated in both sexes. There was complete absence of crossing-over in males in all the experiments which appeared to be the characteristic of marker stock as spontaneous male crossing-over was reported earlier with the same wild stocks when the second chromosome markers were used. Based on the data of karyotypically homozygous F1 females, the map distance between stw-pr was 36.55 map units. The heterozygosity due to a lengthy inversion in 2L increased the level of crossing-over between stw-pr genes of the third chromosome indicating interchromosomal effect. There was a considerable reduction in the rate of recombination between the same markers due to inversion heterozygosity in 3R indicating intrachromosomal effect. However, 3L inversion heterozygosity had no effect on crossover rate. These results provide evidence for intra-and interchromosomal effects of inversions on crossing-over in the third chromosome of D. ananassae. PMID- 1864617 TI - Effect of monoamine antagonists on pretectal evoked analgesia in rat. AB - Mild and brief electrical stimulation of sites in the pretectal nucleus of rat produced analgesia (SPA) of long duration without significant aversion. Intracerebroventricular (icv) administration of 5-HT receptor antagonists methysergide (50 micrograms) and ketanserin (50 micrograms) and the dopaminergic antagonist haloperidol (50 micrograms) had no significant effect on pretectal SPA, but alpha and beta adrenoceptor antagonists phenoxybenzamine (50 micrograms) and sotalol (50 micrograms) on icv injection significantly antagonised the pretectal SPA. The results suggest that pretectal SPA involves activation of central adrenoceptors. PMID- 1864618 TI - Enriched collagen as coadjuvant therapeutic agent in experimental osteomyelitis in dogs. AB - Osteomyelitis was induced in the tibiae of dogs by injecting hemolytic strain of Staphylococcus aureus. Clinical, radiological and histomorphological reactions in the diseased tibiae were studied up to 15 weeks to evaluate the response of infected bone to parenteral oxytetracycline in cases of closed wounds and surgical curettage, antimicrobial irrigation along with parenteral oxytetracycline therapy in animals carrying open wounds. Enriched collagen as a constituent of therapeutic regimen was also administered locally and its efficacy during resolution of osteomyelitis was compared with other treatments. Surgical curettage along with irrigation of lesions was observed to be an effective method for bringing an early recovery in aggravated cases of osteomyelitis. The addition of collagen enhanced the healing process in comparison with non-collagen treated animals. PMID- 1864619 TI - Autoclaved partially decalcified bone as osteogenic substances--an experimental study. AB - A large osteoperiosteal gap was created in rabbit's ulna. A total of 18 allogenic decalbone grafts in left ulnar gap and 20 autoclaved allogenic decalbone grafts on right ulnar gaps were implanted. Five gaps were left unbridged to serve as controls. The results were assessed by clinical, radiological, macroscopic, histological and tetracycline fluorescent studies. It is observed that whereas the decalbone can successfully bridge a large gap in a vast majority of cases; the standard autoclaving of decalbone denatures its proteins which melt and cover the outer surface. The union, incorporation and remodelling of autoclaved decalbone grafts are slower as compared to that with unautoclaved decalbone. PMID- 1864620 TI - Hypersensitivity responses to Staphylococcus aureus infections in rabbits. An experimental study. AB - Repeated weekly infections with S aureus, of bovine mammary origin, for three times evoked an immediate and a delayed type hypersensitivity in rabbits. The skin responses at 6 hr were characterized by oedema, haemorrhages and infiltration of polymorphonuclear cells. While at 24 hr it was dominated by mononuclear cells specially lymphocytes in the dermis. PMID- 1864621 TI - Effect of cycocel and furfuryl amino purine on protein metabolism of pearl millet (Pennisetum americanum L.) under simulated drought conditions. AB - Water stress drastically decreased relative water content and total soluble protein whereas it increased free amino acids, proline and protease enzyme in P. americanum. Treatments with 6-furfuryl amino purine (0.50 mM) and cycocel (60 mM) maintained the levels of soluble protein contents but the applications of furfuryl amino purine decreased free amino acids and free proline under stress conditions. PMID- 1864622 TI - Increased plasma lipidperoxidation in vitamin B-6 deficient rats. AB - Lipidperoxidation in plasma of rats fed with vitamin B-6 deficient diet for a period of 12 weeks was studied with pair-fed controls. Plasma pyridoxal 5' phosphate, alanine amino transferase and aspartate amino transferase, the markers of vitamin B-6 status, were significantly low in vitamin B-6 deficient rats. Plasma malondialdehyde level, conjugated dienes and lipofuscin like pigments were increased in vitamin B-6 deficiency. Increased levels of plasma lipids, calcium, iron and copper were observed in vitamin B-6 deficiency. Plasma susceptibility to lipidperoxidation was maximal in vitamin B-6 deficiency, upon stimulation by the promotors, Fe2+, Fe3+, Cu2+, ascorbate, t-butyl hydroperoxide and hydrogen peroxide. PMID- 1864623 TI - Production and characterisation of a monoclonal antibody to progesterone and its effect on fertility. AB - A monoclonal antibody reacting with progesterone has been raised by fusion of mouse myeloma cells (SP20) and splenocytes of BALB/c mice hyperimmunized with 4 pregnane 3,20 dione conjugated to bovine serum albumin. Association constant of this antibody for binding with progesterone was 0.22 x 10(9) l/mole. The antibody was highly specific for progesterone. A single ip injection of this antibody brought about an antifertility effect which is influenced by genotype. Antibody treatment brought about a significant decrease in the fetal weight and a slight decrease in the plasma progesterone levels. The antifertility effect could be reversed only up to day 3 by exogenous administration of progesterone. PMID- 1864624 TI - Easy criterion for detection of mating in guinea pig. AB - Existing criteria for determining receptivity to mating in female guinea pig has been redefined on the basis of kind of cells present in vaginal smear following its opening. The animals that showed not only cornified but also predominantly cornified cells over the leucocytes show higher sperm positivity rate. It is inferred that continuous cohabitation of these animals invariably leads to successful mating. PMID- 1864625 TI - Histamine H2 receptor mediated relaxation of hamster (Mesocricetus auratus) uterus. AB - Histamine and 4-methyl histamine produced relaxation of KCl depolarized hamster uterus in vitro. The relaxation was selectively antagonized by histamine H2 receptor antagonist cimetidine which failed to antagonize the isoprenaline induced relaxation. The histamine induced relaxation was, further, not mediated through catecholamine release. The study indicated that, as in the albino rat, histamine produces relaxation of the hamster uterus mediated via the H2 receptors. PMID- 1864626 TI - Depletion of ovarian oocytes in sublethally exposed mice to gamma radiation and its modification by 2-mercaptopropionylglycine (MPG). AB - Adult female Swiss albino mice were exposed to 0.6, 1.2 and 2.4 Gy of 60Co gamma radiations in presence and absence of MPG. Quantitative studies were done in serial sections of ovary at 1, 3, 5, 7, 14 and 35 days after exposure. Primary follicles were found to be most radiosensitive. The depletion in the various types of follicles was checked to some extent by prior administration of MPG, but MPG could not prevent the complete elimination of all types of follicles by the last autopsy interval studied. PMID- 1864627 TI - Decrease in dopamine and norepinephrine concentration in different brain regions of mice during progression of Sarcoma 180 tumour. AB - The distribution and concentration of dopamine (DA) and norepinephrine (NE), the catecholamine neurotransmitters, were studied in discrete brain areas of Sarcoma 180 tumour bearing mice. With the progression of tumour, marked depletion of DA and NE concentration was observed in some brain areas richly innervated with dopaminergic and noradrenergic neurons suggesting an inverse relationship between brain CA and tumour growth. Since brain CA influence different important physiological activities like hormonal and immunological functions, it's alteration in brain areas during malignant growth suggests the possibility that the hormonal and immunological alterations during tumour growth is at the level of brain CA. PMID- 1864628 TI - Pre-clinical toxicity of IDPH-791: a new centrally acting muscle relaxant in rats. AB - IDPH-791, a novel centrally acting muscle relaxant, in doses up to 500 mg/kg (po) for 14 days did not result in any appreciable adverse effect on body weight gain, food or water consumption including biochemical and haematologica parameters in rats. Variations observed in the biochemistry and haematology were either comparable to controls or were within normal limits. PMID- 1864629 TI - Gene(s) mapping in a small segment of distal short arm of Y chromosome determine masculinity in humans. PMID- 1864630 TI - Over expression of human apoCIII gene leads to hypertriglyceridemia in transgenic mice. PMID- 1864631 TI - Cell-surface molecules in the regulation of immune responsiveness. AB - This paper reviews current knowledge genetics, structure and function on three categories of cell-surface molecules that affect immune responsiveness. It is focused on human molecules, but some references to murine analogues are made. First, the Major Histocompatibility Complex (MHC) molecules are discussed from the point of view of the associative recognition of antigenic peptides. The multiplicity, polymorphism and heterozygosity of MHC genes is correlated with the fine structure and the function of the molecules encoded by these genes. Second, selected CD molecules that are involved in cell-cell interaction and transduction of signals are discussed and correlated with discrete subsets of T cells, finally, some cell-surface receptors, antigen-specific and interleukin-specific, are analyzes, the effect of various molecules on immune responsiveness is illustrated by the actual experimental data. A minimal or parsimonious of triggering an immune response in which the discussed molecules are involved is described as a starting point for further discussion. PMID- 1864632 TI - C1-INH defect as an example of deficiency disease. AB - Primary defect of C1-inhibitor (C1-INH), the regulatory protein of the initial classical pathway of complement, is the cause of hereditary angioedema. Clinical symptoms involve potentially fatal obstruction of the upper respiratory tract, abdominal pains, and subcutaneous edemas. Since the description of functional tests for C1-INH two types of hereditary defect have been known: type I and type II. Sixteen patients with the type I of hereditary angioedema were diagnosed and treated in our hospital. The onset of the disease occurred between 1.5-12 y. of age. Clinical symptoms were observed in skin, gastrointestinal and respiratory tracts. Mean concentration of C1-INH in sera of 16 patients was 3.25 mg/dl, below 8.75 mg/dl that is the critical for well-functioning C1-INH. Inhibitory activity of C1-INH for C1 esterase in plasma was zero in most of the patients, while it was 0.94 +/- 0.20 U/ml in plasma samples of 91 healthy blood donors. Three modalities of treatment are available: substitution with C1-INH concentrate in acute attacks and antifibrinolytic and/or anabolic drugs for prophylaxis. We have obtained good therapeutic results with epsilon-aminocaproic acid (antifibrinolytic), 2g daily during 3 months, with 6 months intervals. PMID- 1864633 TI - T and B cell defects in common variable immunodeficiency. AB - More than 50 patients with common variable immunodeficiency have been classified into 5 groups representing different blocks in B cell function. To do this, B cells were assessed in vitro by secretion of IgM or IgG in response to anti-IgM and IL-2 or to EBV alone. Some clinical features and the patients' sex ratio correlated with this B cell classification. In vitro attempts were made to identify and overcome these blocks using physiological ligands (e.g. cytokines), and agents that induce transcription (e.g. retinoic acid). The patient group with the most severely affected B cells also contained some patients whose T cells showed depressed DNA synthesis in response to mitogens. In vitro data indicate that the abnormality may be in the T cell itself rather than in monocytes failing to provide essential cytokines (e.g. IL-6). In 3 patients, splenic B cells were able to secrete IgM more effectively than circulating B cells, but still they produced no IgG. PMID- 1864634 TI - Cell-mediated immune functions in a patient with MHC class II deficiency. AB - This report focuses on cell-mediated immune functions in a patient with MHC class II deficiency. The patient described presented with a case of "classical" MHC class II deficiency (T and B cells within the normal range, normal lymphocyte proliferation in response to stimulation with mitogens, gene encoding for MHC class II present, no expression of MHC class II). The absence of MHC class II expression resulted in an incapability of the patient's antigen-presenting cells to function as accessory cells in the presentation of soluble protein antigens, while accessory functions required for the induction of alloantigen-induced lymphocyte proliferation or for the generation of cytotoxic T cells in response to an allostimulus were normal. The patient's T cells responded normally to alloantigenic stimulation and also had the capacity to develop antigen-specific cytotoxic functions. However, the T cells were completely naive with respect to activation by soluble protein antigens, even after presentation by accessory cells derived from the patient's healthy histoidentical brother. In this context it was interesting to note that the patient's CD4-positive cells showed a normal pattern of expression of the 4B4 marker, a marker generally present on memory T cells. These data make it tempting to speculate that in the absence of MHC class II, other cell surface structures may at least partially take over immune functions normally under the control of the MHC class II complex. PMID- 1864635 TI - Unaltered cell proliferation rate of the ataxia telangiectasia lymphocytes dividing in vitro. AB - Lower cell density was found in cultures of ataxia telangiectasia lymphocytes as compared to control lymphocyte cultures. This fits with the earlier observations of decreased incorporation of 3H-Thymidine into lymphocytes of ataxia telangiectasia (AT) patients. However, the finding that there was no significant difference in proliferation rate index between AT and control cultures was unexpected. This may indicate that both cell count and measurements of thymidine incorporation in lymphocyte cultures characterize cell populations distinct from that of proliferating cells. PMID- 1864636 TI - IgG subclasses and antibody response to pneumococcal capsular polysaccharides in children with severe sinopulmonary infections and asthma. AB - A prospective open study was carried out on 30 pediatric patients with most severe chest disease whose serum immunoglobulin levels were normal. The patients entered into the study had had two or more documented episodes of pneumonia, and/or six episodes of bronchitis with fever within a year, and/or severe asthma (steroid-dependent), and/or hospitalization for chest disease for more than 30 days within the year preceding the study. Eleven patients had sinopulmonary infections, 19 had asthma. Twenty patients had low levels of one or two IgG subclasses: 11 were deficient in IgG3, three in IgG4, three in IgG3 + IgG4, and three in IgG2 + IgG4. Patients with low IgG subclass levels were distributed throughout the different clinical entities. These children had significantly longer periods of hospitalization than the patients in whom all IgG subclasses were within the normal range. They suffered more often from sinopulmonary infections. Asthmatic children with low levels of an IgG subclass reported more days with wheezing and needed more steroids than the children without subclass deficiencies. PMID- 1864637 TI - Hypogammaglobulinaemia in low grade B cell tumours; significance and therapy. AB - Bacterial infection is an important cause of morbidity and mortality in patients with B-cell tumors; this is related to their secondary hypogammaglobulinaemia. Two studies of intravenous replacement therapy [IVIg] have been performed in such patients: a crossover study over two years and a randomised, multicentre study over one year. Both involved infusions of IVIg [400 mg/Kg] or an equivalent volume of saline every three weeks for one year. In both studies, serious bacterial infections were considerably reduced by IVIg. Viral and fungal infections were uncommon. In the crossover study bacterial infections were more frequent in periods in which patients serum IgG levels were below the normal range [less than 6.4 g/l]. The sites of bacterial infection were similar in these studies to those in previously published reports, namely respiratory tract, skin, urinary tract and blood. There were a few mild adverse reactions which were related to the rate of infusion, but no serious toxic effects. Haematological parameters were not significantly changed by IVIg at this dose and disease progression did not appear to be changed. PMID- 1864638 TI - The pharmacokinetics of total IgG, IgG subclasses, and type specific antibodies in immunodeficient patients. AB - The advent of immunoglobulin concentrates suitable for intravenous administration has greatly improved the clinical management of patients with a primary immunodeficiency syndrome. However, proper treatment requires understanding of the pharmacokinetics of the infused IgG and its components. We review here the work that has been conducted in this area. In particular, two studies have shown that these concentrates have adequate catabolic properties with regards to total IgG, IgG subclasses, and specific antibodies. We conclude that careful evaluation of the pharmacokinetics of a given IgG preparation is necessary in order to determine an appropriate treatment regimen. PMID- 1864639 TI - MHC allograft immunogenicity--its role in bone marrow transplantation and its constant downregulation. AB - Since 1972 our laboratory has performed a large variety of studies in the rat and mouse models. These have shown that it is possible to achieve MHC fully allogeneic hematopoietic chimerism with complete restitution of immunological reactivity but lasting immunotolerance of donor type cells following transplantation of lymphocyte-purged bone marrow into lethally irradiated recipients. The clinical application of this obvious immunobiological potential is, however, still in its infancy. This is largely due to the belief that graft versus-host reactions and host-versus-graft reactions balance each other out--a view that cannot be upheld. A decisive element in the network of immunoregulation following BMT is the immunogenic strength of the BM. In this context the following bits of information are given: (1) Bone marrow that has been completely purged of lymphocytes loses its allograft immunogenicity to a great extent and may even allow induction of tolerance, whereas unpurged BM is strongly immunogenic. (2) This reduction of alloimmunogenicity is only partially determined by lymphocytes and other MHC class II-expressing cells. (3) By incubating bone marrow with our new cytotoxic monoclonal antibody K31, directed against an epitope located an all human lymphocytes and defined cells of the monocytic lineage, both the alloimmunogenicity and the accessory cell potential of the bone marrow can be greatly reduced. (4) Recent analyses with macrophage cell clones rather than heterogeneous mixtures of BM cells indicate that oncogene transfections may allow us to completely down-regulate their alloimmunogenicity, in spite of unaltered high MHC expression, by genetically downregulating Il-1. In conclusion, it is suggested that MHC allogeneic BMT will become feasible in the human, as it is well-established in preclinical models. PMID- 1864640 TI - Review on therapeutic options in HIV associated thrombocytopenia with emphasis on i.v. immunoglobulin treatment. AB - Thrombocytopenia as a complicating event in human immunodeficiency infection is a rather common hematological disorder and in many aspects resembles idiopathic(immune) thrombocytopenic purpura (ITP). Consequently, treatment of severe cases is similar to treating ITP, but steroids should be administered with particular caution in patients suffering from AIDS. Alternatives to steroids are considered in the present article with emphasis on intravenous immunoglobulin as a means to favourably influence the pathogenic events on the platelet surface. PMID- 1864641 TI - The complement system in HIV disease. AB - Different aspects of the relationship between the HIV infection and the complement system were studied. 1. No significant differences were found between seronegative controls, asymptomatic, and symptomatic (ARC, AIDS) HIV-seropositive patients in the plasma levels of complement components C4, Bf, and C3. 2. Using sensitive ELISA assays, a significant increase was observed in the levels of protein-protein complexes which are formed at the activation of the classical (C1r-C1s-C1-INH) and alternative (C3b-Bb-P) pathways, indicating that both complement pathways are activated in the HIV disease. No significant differences were found, however, in the levels of these complexes between the groups of asymptomatic and symptomatic HIV-infected patients. 3. Artificial immune complexes of synthetic peptides representing some immunodominant epitopes of HIV envelope (gp120, and gp41) proteins, and human polyclonal anti-HIV IgG were found to weakly activate both the classical and alternative complement pathways. 4. An elevated percentage of the lymphocytes carrying a complement activation fragment, C3d, was detected in the blood of HIV seropositive patients as compared to the seronegative controls. No significant positive correlation was found between the percentage of these cells and that of any T cell subsets tested. PMID- 1864642 TI - Do women and men speak in different voices? A comparative study of self evolvement. AB - A comparative study of women's and men's levels of self evolvement was conducted based on Kegan's Constructive-Developmental Theory. The samples for the study were drawn from groups of American women and men in military service in Europe and their dependents, as well as civilians employed by the American military. The participants level of self evolvement was determined by Kegan's Subject-Object Interview. The results indicated that there were no gender differences in levels of self evolvement. Hence, the orientation toward individuation and increased autonomy, which is stereotypically masculine, and the orientation toward attachment and dependence, which is stereotypically feminine, are not necessarily based on innate male or female characteristics. The tendency towards separateness or inclusion may be related more to individual differences and other factors such as the social and cultural environment. PMID- 1864643 TI - Predicates of personal control among middle-aged and young-old men and women in middle America. AB - These analyses explore relationships between the conscious general sense of control and :1) personal evaluations of major life domains (health, spouse's health, marriage, parenting, work, leisure): and 2) spouse's evaluations of life domains, within groups defined by gender and age. Respondents include 101 men and 127 women; all are Caucasian; they reside in a middle-class community in the midwestern United States; they are aged forty-three to seventy-six (M = 56); they are all in long-term marriages, with an average of 4.4 children; and 73 percent had at least one child living at home. Evaluations of life domains included self report satisfaction and investment scales completed after personal interview questions about the domain. There were no gender differences and minimal age differences in levels of sense of control or evaluations of the life domains. However, as expected, multiple regression analyses indicated that the evaluations that contribute to a sense of control vary by gender and be age group within gender group. For men, the sense of control is linked to experiences in work; for younger middle-aged men, satisfaction with health is important; and for older men, investment in marriage is also important. Younger middle-aged women's sense of mastery is tied to satisfaction with mothering and investment in their own health; older women's sense of control is linked to satisfaction with marriage, health, and leisure. Age group patterns may reflect both developmental and cohort effects. PMID- 1864644 TI - The impact of the dream on mental health functioning in the male midlife transition. AB - In the area of adult development, Levinson's notion of the personal Dream is important in understanding the male midlife transition. Levinson suggests that during this period in the life cycle the status of the Dream becomes a prominent issue, as men become increasingly aware of the limits of their achievements. Sixty-four midlife men filled out questionnaires examining whether they had a Dream, and whether they experienced or anticipated experiencing success or failure of that Dream. The Beck Depression Inventory, the IPAT Anxiety Scale, and the Purpose-In-Life Test were included to assess the mental health status of the respondents. The results support the conclusion that whether a man has a Dream, and the degree to which he experiences success in achieving it are significantly related to his mental health status (i.e., depression, anxiety, and purpose-in life) during the midlife transition. PMID- 1864645 TI - Life patterns and age styles in older adults. AB - A biographical approach was used to investigate life themes, life experiences, and personality styles in older adults. Extensive interviews were conducted with fifteen individuals, who sorted index cards with life events and filled out a personality inventory. A typology was developed that distinguished individual life patterns (i.e., specific life themes and life events) and age styles (i.e., personality traits). Three case histories illustrate each of the major life patterns found in the interviews. PMID- 1864647 TI - Fluorocarbon-based blood substitutes: what progress? PMID- 1864646 TI - A comparison of ego identity status transition pathways and change rates across five identity domains. AB - The present retrospective study was designed to explore the question of whether or not ego identity status transition pathways and change rates differ significantly across domains of identity development from adolescence through middle adulthood. A sample of 100 middle- and upper-middle-class New Zealand adults from forty to sixty-three years of age were interviewed regarding the development of values in the areas of vocation, religion, politics, and gender roles, and relationships using an adaptation of the Marcia Ego Identity Status Interview. Raters later assigned an identity status for each year of chronological age for each participant. Preliminary analyses indicated that subgroups of the larger sample differed significantly in terms of identity status transition patterns. Within each of the eight subgroups examined, there were statistically significant differences in transition pathways and change rates across the five identity domains. These findings suggest the importance of examining separate identity domains and controlling for demographic variables in future studies of adult identity development. Results are discussed in terms of Grotevant's process model of identity formation. PMID- 1864648 TI - Endothelin and renal failure. PMID- 1864649 TI - Patient and technique survival for blind and sighted diabetics on continuous ambulatory peritoneal dialysis: a ten-year analysis. AB - A retrospective analysis of patient and technique survival over 10 years in a group of 66 diabetics (40 being blind) and 71 non-diabetics was undertaken. Patient survival profiles showed that the blind diabetics lived longer than the sighted, but for a shorter time than the nondiabetics. In technique success, the sighted diabetics out did the blind and the non-diabetics, long term. Short term, the blind performed better than sighted diabetics. The key to success and longer survival on CAPD depended on motivation on the part of the patient, patient's acceptance of given disability, family (social) support, and willingness on the part of renal care personnel to train the disabled diabetic to perform CAPD. With adequate education and support, blind diabetics did CAPD as well as sighted patients. There was no increased frequency of peritonitis in blind diabetics compared to sighted diabetics. Both blind diabetics and non-diabetics had fewer episodes than sighted diabetics. Intraperitoneal route of insulin administration achieved good glycemic control in diabetic population. Refractory congestive cardiac failure and/or fatal arrhythmias was the most common cardiac cause of death in diabetics on CAPD. PMID- 1864650 TI - Mechanical bridge to cardiac transplantation. PMID- 1864651 TI - Timing for implantation and transplantation in mechanical bridge to transplantation. AB - The implantation of a mechanical blood pump in a deteriorating candidate for heart transplantation is indicated in general if the cardiac index is less than 1.9 L/min/m2 despite maximal inotropic support. Deterioration of end organ function may be taken as a second factor indicating the need for mechanical support as patients with acute onset of shock may react differently from patients with chronic deterioration. Preoperative need for dialysis largely reduces the chances of long-term survival. The time on support should be long enough to normalize or at least improve secondarily damaged organ systems, but with time infectious and thromboembolic complications will increase. So optimal periods for artificial heart support range between two days and four weeks. Age less than 40 years is a positive predictor for outcome in TAH bridging. The general guidelines, however, do not preclude a favourable outcome in complicated cases, as we show in our own series. PMID- 1864652 TI - Prognostic indices of survival in patients supported with temporary devices (TAH, VAD). AB - In an attempt to identify current indications and patient selection criteria for the use of mechanical circulatory support, we reviewed our experience in 83 patients who received a total artificial heart (TAH; n = 43), ventricular assist device (VAD) (n = 13), centrifugal pump (n = 17) or extracorporeal membrane oxigenation (ECMO) (n = 8) as a bridge to transplantation (Group I, n = 50) or for recovery from heart failure (Group II, n = 33). Comparing patients successfully transplanted (n = 20) or weaned (n = 9) who survived initial hospitalization, and those who died on mechanical support, there were no differences in preoperative renal, hepatic or pulmonary functions. Postoperative urinary output and bilirubin levels were the earliest variables affecting survival, and urinary output 24 hours after implant was discriminative in patients who survived (p less than 0.01). Age (above or below 40 years) and modality of terminal heart failure (acute versus chronic) were the most important factors affecting survival in the bridge to transplant group: 82% of young patients with acute decompensation were transplanted and 63% are long-term survivors while all patients over 40 years with chronic heart failure died on mechanical support (MS). In postcardiotomy patients, duration of cardiopulmonary by-pass (CPB) was significantly different comparing survivors with those who died in either bridge or recovery groups and all patients who had a CPB greater than 4 hours died on MS or after transplantation or weaning. In conclusion, preoperative indices indicating reversibility of multiple organ dysfunction remain to be identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864653 TI - Irreversible drop of systemic vascular resistances in patients implanted with a Jarvik total artificial heart. AB - Maintenance of the body's perfusion by a total artificial heart (TAH) may result in physiological alterations to the circulatory system. Little has been said about modifications to systemic vascular resistances (SVR) during TAH assistance. This paper reports on two patients implanted with a Jarvik - 70 cc TAH, who died after 1 and 3 days, both with an irreversible drop of SVR related to a complete loss of vascular tone but not related to sepsis. Activation of multiple cascades of inflammation, triggered by the extracorporeal circulation (ECC), is maintained during TAH support. Desperately sick patients might not be able to face the vaso active situations created by the inflammatory response. PMID- 1864654 TI - Cinematics and sticking of heart valves in pulsatile flow test. AB - The aim of the project was to develop laboratory test devices for studies of the cinematics and sticking behaviour of technical valve protheses. The second step includes testing technical valves of different types and sizes under static and dynamic conditions. A force-deflection balance was developed in order to load valve rims by static radial forces until sticking or loss of a disc (sticking- and clamping-mould point) with computer-controlled force deflection curves. A second deflection device was developed and used for prosthetic valves in the aortic position of a pulsatile mock circulation loop with simultaneous video cinematography. The stiffness of technical valve rims varied between 0.20 (St. Jude) and about 1.0 N/micron (metal rim valves). The stiffness decreased significantly with increasing valve size. Sticking under pulsatile flow conditions was in good agreement with the static deflection measurements. Hence, valve sticking with increasing danger of thrombus formation is more likely with a less stiff valve rim. In the case of forces acting perpendicularly to the pendulum axis, the clamping mould-point of the valve can be reached, followed by disc dislodgement. PMID- 1864655 TI - Bioartificial polymeric materials obtained from blends of synthetic polymers with fibrin and collagen. AB - A new class of biomaterials, called "bioartificial polymeric materials", was prepared blending a segmented polyurethane (PU) with fibrinogen (FBNG); and poly(acrylic acid) (PAA), poly(acrylamide) (PAAM), poly(vinyl alcohol) (PVAL), with collagen (CLG), respectively. The PU-FBNG material was processed through a spraying, phase-inversion technique to fabricate porous tubular conduits. FBNG was subsequently converted into covalently cross-linked fibrin (FBN) through the action of thrombin (Th), fibrin-stabilizing factor (FSF), and calcium ions. Differential scanning calorimetry (DSC) showed the cross-linked blend was more stable than native cross-linked FBN. Tensile behaviors of the PU-FBN materials closely matched those of a natural artery on varying the ratio PU/FBN. Implantation experiments in the rat model showed a mature internal capsule and good tissue organization of PU-FBN (50%) grafts in the regenerated arterial wall. However, 50% of FBN did not assure adequate mechanical resistance, and aneurysmal changes were seen in some grafts. DSC of CLG-based materials, processed by casting, showed that the synthetic component offered definite advantage compared to the CLG denaturation temperature, particularly noticeable for CLG-PAA and CLG PVAL blends. Material advantages and drawbacks are discussed. PMID- 1864656 TI - Apheresis-elutriation program for adoptive immunotherapy with autologous activated monocytes in cancer patients. AB - Human blood monocytes (Mo) and monocyte-derived macrophages (M phi) are known to be potent antitumor cytotoxic effector cells through activation with recombinant human interferon gamma (rIFN-gamma), bacterial muramyldipeptide or the synthetic derivative muramyltripeptide phosphatidylethanolamine entrapped in liposomes (L MTP-PE). Large-scale generation of ex vivo activated Mo from the blood of cancer patients proved feasible. We report our experience with a fixed rotor speed counterflow centrifugation elutration (CEE) procedure using the newly available Beckman high capacity JE-5.0 rotor system that reproducibly isolates up to 1.0 1.5 x 10(9) Mo with greater than 90% purity, in suspension and functionally intact derived from peripheral blood mononuclear cell-enriched suspensions obtained by leukapheresis (LP) from healthy volunteers and cancer patients. The semiclosed, easy to handle CCE system, was adapted to a sterile technique that permitted clinical trials in adoptive monocyte immunotherapy. Freshly isolated Mo did not lose morphological or functional integrity and had no spontaneous activation. Their abilities to become activated to the cytotoxic state after 18-h stimulation with 500 U/ml rIFN-gamma or 1 microgram/ml L-MTP-PE and to differentiate into matured M phi in vitro were not altered. The system was therefore used to isolate large numbers of Mo for a phase I clinical trial of intraperitoneal immunotherapy with L-MTP-PE activated autologous Mo in nine patients with peritoneal carcinomatosis. Each patient received weekly Mo infusions (n = 5) with an intrapatient dose escalation schedule (from 10(7) to 10(9) Mo). Toxicities were mild including fever, chills and abdominal pain. There was no treatment-induced thromboembolic event or capillary leak syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864657 TI - Membrane plasmapheresis raises the serum concentrations of pseudouridine. PMID- 1864658 TI - Percutaneous balloon aortic valvuloplasty during pregnancy. AB - Severe aortic stenosis may potentiate sudden life threatening complications during pregnancy. We report a case of successful percutaneous balloon aortic valvuloplasty in a pregnant patient with severe symptomatic aortic stenosis due to congenital bicuspid aortic valve at 14 weeks' gestation. Use of percutaneous valvuloplasty allowed asymptomatic progression of the pregnancy to term and normal delivery of a healthy 2920 g infant. PMID- 1864659 TI - Valvar vegetations in the neonate due to fetal endocarditis. AB - Mass lesions were observed on the tricuspid valve by cross-sectional echocardiography in 5 neonates, 4 of whom presented with fetal distress. Four went on to develop severe respiratory distress, 3 from meconium aspiration and 1 from hyaline membrane disease, with 2 deaths despite intensive treatment. Autopsy confirmed meconium aspiration pneumonia. Sterile, unorganised vegetations were seen on the tricuspid valve (and in 1 infant the mitral valve too). Perinatal factors such as hypoxia, haemodynamic and coagulation disturbances may have contributed to the formation of the vegetations and may reflect the severity and refractoriness of persistent pulmonary hypertension. PMID- 1864660 TI - Transoesophageal echocardiography in diagnosis of aberrant coronary artery. AB - Aberrant origin of the main stem of the left coronary artery from the right sinus of Valsalva caused angina of effort in a 40 year-old patient. Diagnosis was revealed by transoesophageal echocardiography and confirmed by selective coronary angiography. Aorto-coronary bypass was performed in order to prevent the recurrence of myocardial ischemia. PMID- 1864661 TI - Hydatid cyst of the heart and pericardium. AB - Between 1977 and 1988, six young patients (average 22 years) underwent surgery for cardiac echinococcosis. Three had a single cyst and the others had multiple cysts which ruptured into the pericardium. The diagnosis was always confirmed by cross-sectional echocardiography and cardiac angiography. Surgery was always performed through median sternotomy using cardiopulmonary bypass. Morbidity and mortality were nil and late results were satisfactory. PMID- 1864662 TI - Doppler evaluation of a left atrial myxoma. AB - We present a detailed Doppler evaluation of a left atrial myxoma. Doppler recordings varied considerably with the position of the patient and of the sample volume. Maximum obstruction to flow was observed in the left lateral position; but no gradient was present when sitting upright. These findings provide a haemodynamic explanation for the positional variation of murmurs characteristic of atrial myxomas. PMID- 1864663 TI - Abnormal systolic atrioventricular flow related to incoordinate motion of the ventricular wall after the Fontan operation. AB - The development of abnormal flow has been described in patients with incoordinate motion of the ventricular wall. In all cases so far documented, these abnormal patterns of flow have been restricted to the ventricular cavity, and the atrioventricular valve remained closed. We identified a patient after a Fontan operation in whom the degree of ventricular mural incoordination was of such severity that the atrioventricular valve remained open and atrioventricular flow occurred for 140 msec after the onset of QRS complex. As far as we know, this phenomenon has not previously been described. PMID- 1864664 TI - Conventional right sided chest leads fail to identify small right ventricular infarctions. PMID- 1864665 TI - A correlation between the structure of myocardial cells and prolonged Q-T interval in young rats. AB - In the present study, we examined the electrocardiogram and the structure of myocardial cells in young rats at different postnatal ages. The offspring of rats were sacrificed on different postnatal days following electrocardiographical recordings, and sections of their hearts were examined microscopically. In a number of newborns, we observed definite prolongation of the Q-T interval in the electrocardiogram on the first day of life. Normal shortening of the Q-T interval with age was demonstrated in the majority of the offspring while, in some of them, the Q-T interval remained prolonged. In the "affected" offspring, which exhibit a typical pattern of Q-T prolongation with clear ST segment, definite retardation of histological differentiation of the myocardium was found at various ages. In these cases, there were large numbers of "myoblasts" scattered between normal myocytes in different parts of the ventricular walls and septum. These myoblasts were rarely identified in newborns and offspring with a normal Q T interval. Our results clearly show a correlation between the ratio of persistence of undifferentiated myoblasts at any age and the typical prolonged Q T pattern in the electrocardiogram (r = 0.9). Due to the possible clinical significance, the hearts of patients with prolonged Q-T syndrome should be examined so as to reach for abnormal differentiation of the myocytes. PMID- 1864666 TI - Coronary angioplasty with second generation Monorail catheters. AB - The Monorail system (Schneider) consists of a balloon catheter in which the guidewire passes through the balloon itself, exits the catheter proximal to the balloon, and runs alongside its small shaft (3 French) through the length of the guiding catheter. It offers distinct advantages over conventional systems of coronary angioplasty. It facilitates contrast injections and permits rapid balloon exchanges. This system was used for coronary angioplasty in 273 unselected consecutive patients (age 59 +/- 10, mean 35 to 73 years). There were 216 patients (84%) undergoing single-vessel and 57 patients (16%) with multi vessel coronary angioplasty. A total of 335 coronary stenoses were dilated, which included 35 total occlusions. The size of balloon used ranged from 2.0 to 4.25 mm (3.0 +/- 0.5 mm) and the severity of stenosis was 85 +/- 11%. Technical success was defined as a residual stenosis of less than 50% as determined angiographically. Clinical success was defined as technical success, and absence of a major inhospital complication defined as absence of myocardial infarction, lack of need for coronary arterial bypass surgery, and survival. The Monorail system was technically successful in 294/300 stenotic lesions (98%). It was clinically successful for 281 lesions (94%). Of the 35 total occlusions, technical success was obtained in 25 (71%). The residual stenosis of successful cases was 26 +/- 21%. The Monorail system was also successful in 5 patients with stenosis of more than 90% in whom conventional systems failed. The complications included acute occlusion causing acute myocardial infarction in 13 cases (5%), emergency coronary arterial bypass surgery in 1 patient (0.4%), and death in 4 patients (1.5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864667 TI - Different effects of acute intravenous administration of k-strophanthidin and prenalterol on the diastolic phase of left ventricular function in patients with coronary arterial disease. AB - In 21 patients with coronary arterial disease, and with maintained (or mildly depressed) systolic function, we studied the effects of two well-known inotropic agents, namely prenalterol and k-strophanthidin, on the diastolic phase. Selected variables of both systolic and diastolic function were assessed at controlled heart rate by cardiac catheterization and left ventriculography before and after acute intravenous administration of the beta 1 agonist prenalterol (35 micrograms/kg for 3 min) and of k-strophanthidin (0.008 mg/kg for 5-10 min). Ten patients received prenalterol, and 11 patients were injected with k strophanthidin. Administration of prenalterol induced a remarkable diminution of end-systolic volume index (mean values from 41.8 +/- 11.9 to 32.2 +/- 10.4), while k-strophanthidin showed only a tendency towards a decrease (mean values from 43.4 +/- 13.2 to 40.7 +/- 15.1). After k-strophanthidin, we did not observe any significant changes in the peaks of maximal rate in volumetric increase during filling phase whereas, after prenalterol, a noteworthy increase of the first peak was accompanied by a significant decrease of the second peak. The lowest and end filling left ventricular pressures were decreased by prenalterol (mean values from -0.8 +/- 0.1 to -2 +/- 0.5 and from 10.6 +/- 4.6 to 4.1 +/- 1.1 respectively), whereas k-strophanthidin increased left ventricular end diastolic pressure (mean values from 11.6 +/- 4.3 to 17.1 +/- 9.1). Prenalterol induced a relevant increase of ejection fraction (mean values from 0.52 +/- 0.1 to 0.61 +/- 0.008), whereas k-strophanthidin produced only a nearly significant (P less than 0.06) mild increase (mean values from 0.51 +/- 0.06 to 0.54 +/- 0.09).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864668 TI - The coronary arteries of the transplanted human heart: studies of the development of disease based on serial angiography. AB - 291 coronary angiograms were performed routinely 1 to 8 years after cardiac transplantation in 116 patients operated on at Papworth Hospital between January 1979 and September 1986. In this setting, as in others, angiography tends to underestimate the amount of disease present, and the patterns of angiographic abnormality are various. The actuarial probability of freedom from angiographic evidence of coronary occlusion is 79% at 2 years, 76% at 3 years, 60% at 4 years, 57% at 5 years. We have defined two disparate groups designated 'fast disease' and 'slow disease', being respectively those who have angiographic and/or pathologic evidence of disease at two years, and those who have normal coronary angiograms at 5 years. In comparing features of these two groups, donor age, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglyceride level differ, though significantly only for the high density fraction. PMID- 1864669 TI - Cardiac rhythm after Mustard repair and after arterial switch operation for complete transposition. AB - We compared the prevalence of arrhythmias among the first consecutive 45 patients with complete transposition (concordant atrioventricular and discordant ventriculo-arterial connexions) after arterial switch operation and the last 47 patients after Mustard repair in infancy. Both groups had 24-hour Holter electrocardiographic studies at similar periods of follow up (24 +/- 14 and 25 +/ 18 months). A second group of patients undergoing the Mustard procedure had been repaired at an older age before 1981. They were studied to determine the frequency of disturbances of rhythm during later postoperative follow-up (85 +/- 24 months). Symptomatic brady-/tachyarrhythmia syndrome never occurred after the arterial switch and only once in the group of patients repaired by the Mustard procedure in infancy, but developed at a late stage (69 +/- 28 months); five times in the group of patients having Mustard's repair at an older age. In addition, Holter monitoring did not detect bradyarrhythmias indicating sinus node dysfunction in a single patient after the arterial switch, but did so to a similar extent in both groups having the Mustard procedure (recent: n = 14; older: n = 18). Three cases of the group of older patients undergoing a Mustard operation developed complete atrioventricular block during follow-up. Normal findings were present in 93% of the cases after arterial switch, but in only 51% of the cases with a similar follow-up repaired by the Mustard procedure, and in 29% of the group having the Mustard repair at an older age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864671 TI - Electrophysiologic-structural correlations in chagasic aneurysms causing malignant arrhythmias. AB - We studied the structure and ultrastructure of three chagasic aneurysms, the excision of which abolished malignant arrhythmias. Chronic recurrent ventricular tachycardia often occurs in patients with chagasic aneurysms, and ventricular mapping indicates that these arrhythmias originate in regions adjacent to those aneurysms. In our patients, ventricular tachycardia had been refractory to medical treatment. During surgery, epicardial and endocardial mapping showed abnormal potentials. Sutures were placed in the areas of resection, their sizes approximating those of earliest activation so that these sites could be identified. The myocardium showed chronic inflammatory reaction, myocytolysis and fibrosis. The presence of "islets" was common (normal, "early" damaged or "established" necrotic myocytes surrounded by fibrous tissue). The "early" lesions were predominant at the previously identified areas of arrhythmogenic activity. The ultrastructural studies showed hypertrophy of myocytes and partial or complete loss of myofibrils, swelling of mitochondria and disruption of mitochondrial cristae, accumulation of lipofuscin granules, and intracellular oedema. A most striking alteration was the thickening of the basement membranes of myocytes and vascular endothelial and smooth muscle cells. The interlaced fronts of respectively healthy (fast conducting) and "early" damaged (slow conducting) myocytes seen in serial sectioning produced an ideal configuration for reentry circuits. The final proof that the arrhythmias originated in these endocardial regions was their abolition by resection of the aneurysm. PMID- 1864670 TI - Relationship of immunosuppression and serum lipids to the development of coronary arterial disease in the transplanted heart. AB - Coronary arterial disease in the cardiac allograft has emerged as the most serious long term complication of cardiac transplantation. The influence of patient-related and other potential risk factors on the development of coronary arterial disease at 1 year subsequent to cardiac transplantation was examined in 207 recipients. The mean age of donors in patients with coronary arterial disease was 28.5 +/- 9.5 years, compared to 22.6 +/- 7.9 years in patients without coronary arterial disease (P less than 0.01). Eight of the 35 patients who received immunosuppression by means of prednisone and azathioprine developed coronary arterial disease compared to 5 of the 172 patients who were treated with cyclosporin and azathioprine without routine oral prednisone (P less than 0.01). The relationship of levels of serum lipids to the subsequent development of coronary arterial disease was investigated in 95 patients with angiographically normal coronary arteries one year after cardiac transplantation. The cumulative probability of coronary arterial disease in those with total cholesterol greater than 5.8 mmol/l was 9.3% at 2 years (n = 40), 24.4% at 4 years (n = 21) and 45% at 4 years (n = 9) compared with 4.3% at 2 years (n = 45), 7.4% at 3 years (n = 32) and 14% at 4 years (n = 14) in those with a total cholesterol less than 5.8 mmol/l (P less than 0.05). Similarly, the incidence of coronary arterial disease was increased in patients with serum triglyceride greater than 1.4 mmol/l (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864672 TI - Prognostic significant of indium-111 antimyosin antibody uptake in patients with dilated and hypertrophic cardiomyopathy. AB - The prognostic significance of myocardial uptake of indium-111 antimyosin was evaluated in 15 patients with idiopathic cardiomyopathy: 10 patients with dilated cardiomyopathy and 5 patients with hypertrophic cardiomyopathy. Seven of the 10 patients with dilated cardiomyopathy showed positive images; three of these 7 patients with strongly positive scans died within 3 months after scintigraphic examination. Four of the 5 patients with hypertrophic cardiomyopathy showed positive images; two of these patients with dilated left ventricle had prominent positive scans and higher heart to lung ratio. One of these two patients died 12 months after antimyosin scan. The heart to lung ratio of antimyosin uptake in total patients was correlated with left ventricular end-diastolic dimension (r = 0.51, P less than 0.05), end-systolic dimension (r = 0.57, P less than 0.05) and ejection fraction (r = -0.60, P less than 0.05) measured by echocardiography. Although the number of patients is small and the study is preliminary, indium-111 antimyosin antibody imaging could be of value in establishing prognosis of patients with dilated and hypertrophic cardiomyopathy, in selecting patients for cardiac transplantation, and in evaluating the effects of therapeutic interventions. PMID- 1864673 TI - Senile systemic amyloidosis: a clinico-pathological study of twelve patients with massive amyloid infiltration. AB - Hearts from 12 patients, 82-92 years old, with immunohistochemically verified pronounced senile systemic amyloidosis, were studied postmortem. Sections from the left ventricle, atrioventricular and sinus nodes and atrioventricular bundle were studied using the light microscope. The weights of the hearts varied between 310 and 870 grams. In the studied parts of the conduction system, the amounts of amyloid were considerably smaller than in the surrounding myocardium. Clinical data were taken from available case records. Eight of the patients had a history of uncomplicated congestive heart failure, but only two had been in hospital with cardiac symptoms prior to their last admission. The electrocardiogram showed atrial fibrillation in nine cases, left bundle branch block in three, right bundle branch block in two and left anterior hemiblock in one. No evidence of atrioventricular dissociation was seen and, in no case, was death considered to be due to conduction disturbances. Amyloidosis was a contributing cause of death in 7 patients, while the remaining patients died of other diseases. Amyloidosis is rarely diagnosed before death and was not suspected during life in any of our patients. PMID- 1864674 TI - Hypertrophy of surviving myocytes overlying the infarct in human old myocardial infarctions with abnormal Q waves. AB - The time course of hypertrophy of surviving myocytes overlying the infarct after the onset was examined and the hypertrophy was analyzed in relation to the transmural extent of infarct in 34 autopsied hearts with Q wave infarction. The 34 hearts were divided into 4 groups according to the length of time between the onset of infarction and death. This was less than 5 days in group 1 (n = 10), 20 30 days in group 2 (n = 7), 40-60 days in group 3 (n = 7), and 12-24 months in group 4 (n = 10). To clarify the regional hypertrophy of myocytes overlying the infarct, the size of the surviving myocytes in the outer third of the left ventricular wall in the 1-cm wide central zone of the infarct was compared with that of the myocytes in the outer third of the left ventricular wall without infarction (control wall) in the same heart. To exclude factors which stimulate the hypertrophy of the whole left ventricle, the ratio of the monocyte diameter in the infarcted wall to that in the control wall was examined. It was 1.0 +/- 0.0 (mean +/- SD) in group 1, 1.0 +/- 0.1 in group 2, 1.2 +/- 0.1 in group 3, and 1.3 +/- 0.1 in group 4. The ratio was significantly higher in group 3 than in group 1 and 2, and was highest in group 4. In group 4, the corrected percentage transmural extent of infarct indicating the original transmural extent of infarct at the acute stage was 63 + 8%, and this transmural extent correlated positively with the ratio of myocyte diameter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864675 TI - Lower limb amputations for vascular insufficiency. PMID- 1864676 TI - Mothers of children with severe mental retardation: maternal pessimism, locus of control and perceived social support. PMID- 1864677 TI - Conceptions of hearing impairment in students. PMID- 1864678 TI - Psychological characteristics of drug abusers: implications for treatment and rehabilitation. PMID- 1864679 TI - Origin of the avian glycogen body: I. Effects of tail bud removal in the chick embryo. AB - The tail bud was removed from chick embryos at stage 16-17 in a first study directed to learn of the origin of the glycogen body in the lumbosacral spinal cord of birds. Results of tail bud removal and chorio-allantoic grafting of caudal portions of the embryo containing the tail bud or the neural tube suggest that the glycogen body does not arise from the tail bud, but from the preexisting neural tube craniad or anterior to the tail bud. The stem cells of the glycogen body are most likely among those components of the anterior portion of the lumbosacral neural tube derived from primary neurulation. PMID- 1864681 TI - Biorhythms as a possible regulator of longevity. PMID- 1864680 TI - Effects of nutrient intake and sexual age of the dam at mating on fetal development in swine. AB - Fifty-four Duroc gilts (mean wt = 88 kg, mean age = 164 d) were fed a 15% protein diet either ad libitum (F) or at a rate of approximately 50% of ad libitum daily (1.8 kg: L) prior to mating at either second (Exp. 1) or first (Exp. 2) observed estrus. Gilts were checked for estrus twice daily with a mature, active boar, mated at the appropriate estrus, and fed 1.8 kg of the prebreeding diet per gilt daily until slaughter between 42 and 49 days of gestation, mated gilts were slaughtered and measurements taken on fetuses and reproductive organs. In Exp. 1, fetal weight per day of gestational age (FetWDA), placental weight (PLW), crown to-rump length (CRL) and uterine space per fetus (SP) were greater for fetuses from L gilts than F gilts (all P less than .05) with no difference in number of fetuses (P greater than .05). In Exp. 2, FetWDA was greater for fetuses from F gilts than L gilts (P less than .05), however there was no difference due to level of feeding for PLW, CRL and SP (all P greater than .10). Fetal weight (FW) was highly correlated with CRL indicated that a cubic relationship existed (both r = .97). In both studies, male fetuses grew more rapidly than female fetuses (P less than .05). These studies indicate that pre-breeding nutritional status and sexual age of the dam at conception have differential effects on fetal growth rate, but relationships among FW and CRL are not readily altered by pre-breeding level of feeding or sexual age of the dam at conception.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864682 TI - A longitudinal investigation of the effects of experience on the behavior of aging mice. AB - The effects of differential experience over most of the adult lifespan of mice were examined utilizing longitudinal designs. Repeated experience with nest building was contrasted with one-time only experience at various age levels from 4 to 24 months of age. The results suggest that the presence or absence of repeated exposure to nest building opportunities affects stability of nest building, while open field activity remains stable regardless of experience and vitality declines regardless of experience. Because nest building at maturation is not influenced by prior experience, the effect of differential experience during the course of aging is not interpreted as a reflection of differential initial acquisition of the behavior. Rather, performance differences are interpreted as providing evidence for the differential maintenance of neural integrity of the underlying mediator for the behavior. The discrepancy among the patterns of change for nest building, open field activity, and performance on the tightrope test is interpreted as reflecting differences in the relative importance of deterioration of the underlying neural mediators in comparison with decreases in muscular strength and flexibility. Implications for design issues in animal research in aging are discussed. PMID- 1864683 TI - Concentration of insulin-like growth factors (IGF-I and IGF-II) in tissues of developing lean and obese pig fetuses. AB - An ontogeny study of lean and pre-obese pig fetuses was conducted to evaluate the temporal and genetic influence on the relationship between growth and IGF production. At 70, 90 and 110 days of gestation, three fetal pigs were obtained from each of three obese and lean dams. The heart, kidneys, lungs, liver and one biceps femoris muscle were removed, weighed, frozen and extracts prepared. For all the organ and tissue weights, there were significant (P less than .001) main effects of genotype (G) and fetal age (A). At each fetal age, pre-obese fetuses had lighter organ and tissue weights. The content of IGF's in serum and various tissues and/or organs was also determined. Main effects of A and G were significant (P less than .05) for liver and lung IGF-I and muscle IGF-II concentrations. Main effects of G were significant (P less than .01) for liver IGF-II whereas muscle IGF-I and lung IGF-II concentrations were only affected by fetal age (P less than .01). Overall, liver IGF-I and II and muscle IGF-II concentrations were higher in lean fetuses (P less than .01). Serum IGF-I concentration increased (P less than .01) with fetal age and was independent of fetal strain. Serum IGF-II concentration increased with age (P less than .01) in lean but not pre-obese fetuses. Therefore, these studies demonstrate genotype dependent growth factor concentrations in tissues and organs of developing fetuses. Finally, serum concentration of IGF's were strongly correlated (positive) with overall growth but were not strongly correlated with tissue and organ concentration of IGFs. PMID- 1864684 TI - Influence of method of model fitting and gender on estimated parameters for the relationship between starvation heat production and body size in the domestic fowl. AB - The relationship between starvation heat production (SHP) in kJ/d and body weight (W) in kg for domestic fowl was examined with compiled calorimetric data for 294 fowls (Johnson and Farrell, 1985). Linear regression analyses using ordinary least squares methods were performed before and after transformation of the data to a logarithmic scale (base = 10). Coefficients of determination (R2) were similar for untransformed and log-transformed data (R2's = .56 and .53, respectively). The slopes for untransformed data of males and females were different (P less than 0.033). When the model parameters for: SHP = b0 Wb1 were derived from log-transformed data, there were no significant differences in exponents for males vs. females (P greater than .95). However, when the coefficients were estimated using non-linear regression techniques, a difference was detected at the level of P = 0.072. It was determined that there is no advantage in describing the relationship of SHP as a non-linear function of W, nor is it appropriate to express physiological variables as a ratio of weight raised to some mass exponent without statistical justification. Using W or W2 as a covariable for the statistical analysis of physiological data would produce equally acceptable determinations of significance. PMID- 1864685 TI - Major histocompatibility complex antigen expression on lymphocytes from aging strain A mice. AB - Molecules encoded by the major histocompatibility complex (MHC) are crucial for the proper functioning of the immune response. In this study, the levels of class I and class II major histocompatibility antigens on lymphocytes from strain A mice were measured as a function of age. Class I protein levels increased significantly on both peripheral blood and spleen (T cells and B cells) lymphocytes with age. This increase in MHC class I protein levels was accompanied by an increase in class I mRNA levels. On the other hand, class II protein levels did not show a significant change with age. Moreover, while the percentage of class I-expressing spleen lymphocytes stayed at a steady-state level of 100% with age, the percentage of class II-expressing spleen lymphocytes decreased from 85% in young animals to 70% in old animals. This decrease was due to a decrease in the relative proportion of B cells compared to T cells in the spleen lymphocyte population of old mice. When class II mRNA levels were measured, it was found that these levels decreased markedly with age. Overall, it is clear that the regulation of MHC class I and class II expression changes with age in A strain mice. Since optimal levels of MHC expression are crucial for the proper functioning of cellular and humoral immune responses, it will be most interesting to understand how the control of MHC gene expression changes with age and whether MHC gene expression can be modulated in old individuals to restore better immune function. PMID- 1864686 TI - Japan's new Mental Health Law: more light shed on dark places? AB - The legislative response to the crisis in the Japanese mental health care system has, on the one hand, been prophylactic. The major thrust of legal reform has been to prevent the human rights abuses which occurred all too easily under the former structure of legal regulation. Thus, a new category of admission, voluntary admission, has been recognized and promoted as the preferred hospitalization procedure. Standards for the physical treatment of patients have been promulgated, and procedures instituted for review of periodic reports and requests for discharge or improved physical treatment, with notification given patients as to their rights under the law. The model chosen for this new system of safeguards is far from a thorough-going legalistic model. Patients have no right to a judicial hearing. Even the informal hearing provided may be limited, or eliminated in the PRB's discretion. Reliance is placed upon the PRB and the Designated Physicians to protect the patient's rights and to prevent improper admission and treatment. However, the PRB is not independent. It is appointed by the prefectural governor and its functional units, the review panels, are controlled by Designated Physicians judging, in most cases, decisions or actions taken by other Designated Physicians. The individual Designated Physicians to whom are entrusted many of the critical diagnostic, therapeutic and physical treatment decisions respecting an individual patient will in many cases be, moreover, an employee of the hospital concerned. Beyond this closed administrative process, there are, in legal terms, only the extraordinary powers of the governor or Minister of Health and Welfare to detect improper admissions or physical treatment and remedy them by order. There are no appeal procedures and no access to the courts specifically provided within the Law's system of safeguards. Certain areas of concern, such as the right to refuse certain types of medical treatment, are not addressed in the Law at all. The new system of legal safeguards reflects the continuation of a paternalistic, medical model in which abuses will be more difficult to hide from the light of the new, carefully channeled and limited administrative review process. Related to but even beyond the question of the prevention of human rights abuses, the new Law is also concerned with the affirmative realization of the most important right of the mental patient, the right to effective treatment and a return to a normal place in society.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864687 TI - Competency to consent to voluntary hospitalization: a therapeutic jurisprudence analysis of Zinermon v. Burch. PMID- 1864688 TI - Jury selection in malpractice suits: an investigation of community attitudes toward malpractice and physicians. PMID- 1864689 TI - Length of detention in matched groups of insanity acquittees and convicted offenders. PMID- 1864690 TI - The crime preventive effect of psychiatric treatment on mentally disordered offenders in Sweden. PMID- 1864691 TI - Psychiatric admission of family violent versus nonfamily violent patients. PMID- 1864692 TI - Of nightmares and sexual monsters: struggles around child abuse in Australia. PMID- 1864693 TI - Sexual abuse allegations in child custody disputes. PMID- 1864694 TI - Prediction of competency to stand trial: contribution of demographics, type of offense, clinical characteristics, and psycholegal ability. PMID- 1864695 TI - Using medical registries and data sets for technology assessment. PMID- 1864696 TI - Technology assessment in the Connecticut Tumor Registry. AB - A search of literature using the Connecticut Tumor Registry (CTR) for technology assessment produced eight articles. These articles represent a small but apparently increasing percentage (2%) of total CTR publications. By keeping pace with the development and dissemination of medical technologies, the population based CTR has been useful for assessing them, especially their adverse effects. PMID- 1864697 TI - Use of the SEER Cancer Registry for technology assessment. AB - The Surveillance, Epidemiology, and End Results (SEER) cancer registry contributed to technology assessment by providing population-based samples for detailed case-control studies, by serving as the control group in comparisons with various experimental groups, by allowing an assessment of selection bias in clinical trials, and by facilitating evaluations of classification and coding systems. PMID- 1864698 TI - Technology assessment in the Normative Aging Study. AB - This review of publications based on data from the Veterans Affairs Normative Aging Study identified four articles that were considered assessments of health care technologies. Three evaluated methods for research on body composition, the fourth studied ventricular size in patient with presenile dementia. Several additional articles are discussed that provided data on baseline values or risk factors for disease that might be useful in generating hypotheses to be tested in later assessments of technologies. PMID- 1864699 TI - Technology assessment in the Veterans Administration Dental Longitudinal Study. AB - Of the 52 studies emanating from the Veterans Affairs Dental Longitudinal Study, 6 were identified as technology assessments. Three of these studies evaluated dental radiographs used for the diagnosis of oral lesions. Two studies compared alternative technologies for the replacement of missing teeth, and one reported the effects of NSAIDs on alveolar bone loss. Four additional articles are discussed that provide data that will be useful in future assessments of dental technologies. PMID- 1864700 TI - Technology assessment in the Framingham Heart Study. AB - To assess the role of observational data bases in technology assessment, we examined 26 articles from the Framingham Heart Study that evaluated a technology, therapy, or predictive instrument. These assessments were grouped into four categories: (a) the study of a technology voluntarily in use by the cohort, (b) the application of an external technology to members of the cohort, (c) the use of the Framingham results to evaluate an unrelated assessment, and (d) the use of the results to validate predictive instruments from other studies. Factors that contribute to the ability of the study to assess voluntary and external technologies include long-term follow-up, a stable cohort, and storage of such nonnumeric data as cardiograms and blood samples. Framingham results have been used to determine outcome measures in later studies. Although the Framingham Study was not designed to assess a technology, we found that large-scale, observational data bases can and do contribute to technology assessment. PMID- 1864701 TI - Technology assessment in the Coronary Artery Surgery Study. AB - The majority of the 26 technology assessment articles from the Coronary Artery Surgery Study (CASS) follow the original purpose of the registry and evaluate the therapeutic capabilities of coronary artery bypass graft surgery. However, these registry data have also been used to identify risk factors for cardiovascular disease, to test diagnostic technologies, and to evaluate technological processes. Consideration of quality of life issues and the availability of cost data provide valuable additions to the continued use of the CASS for technology assessment. PMID- 1864702 TI - Use of a clinical data registry to evaluate medical technologies. Experience from the International Bone Marrow Transplant Registry. AB - We reviewed the 18 disease-specific evaluations that used the data base of the International Bone Marrow Transplant Registry to determine the effectiveness of alternative strategies for bone marrow transplant. We identify 17 treatment variables that physicians can control and report the associations between these variables and five clinical endpoints: stable engraftment, graft-versus-host disease, development of interstitial pneumonia, relapse, and disease-free survival. We also suggest policies to promote active participation in establishing and operating a registry. PMID- 1864703 TI - Using medical registries and data sets for technology assessment. An overview of seven case studies. PMID- 1864704 TI - Using administrative data bases for technology assessment in health care. Results of an international survey. AB - This study assesses the nature, use, and quality of large administrative data bases available in different countries for technology assessment in health care. Using postal questionnaires, data were collected describing 91 data bases from 15 countries. Current uses are promising, but more efforts are needed if the full potential of administrative data files is to be tapped. PMID- 1864705 TI - A brief introduction to influence diagnostics in regression. AB - Statistical analyses that involve regression methods often encounter data in which some observations have substantial influence. This article presents a nontechnical discussion of influence and of two techniques, based on leaving out each individual observation in turn, for diagnosing influential data. An example illustrates the techniques in an analysis of recurrence rates in endoscopic treatment of bleeding peptic ulcers. PMID- 1864706 TI - Molecular events in measles virus infection of the central nervous system. PMID- 1864707 TI - Molecular biology of cytokine effects on vascular endothelial cells. PMID- 1864708 TI - Perinephric inflammatory process following extracorporeal shock wave lithotripsy. AB - A patient with large branched staghorn calculi was treated with ESWL. She suffered from recurrent urinary tract infections. Following ESWL she developed a perinephric abscess, which necessitated percutaneous drainage. The clinical course is described and a possible pathogenesis of perinephric abscess following ESWL is suggested. PMID- 1864709 TI - Nephrocolic fistula in association with a staghorn calculus discovered intraoperatively. AB - A rare case of spontaneous nephrocolic fistula discovered intraoperatively in a patient with a staghorn calculus is presented with a review of the literature. PMID- 1864710 TI - Clinical radiological management of an uncommon perinephric abscess. AB - The authors describe an uncommon case of a huge perinephric abscess with a gas fluid level occupying the upper left abdomen. A rational sequence of radiological diagnostic methods such as plain film, ultrasound, CT, and combined retrograde urogram with contrast filling of percutaneous drainage led to correct management. PMID- 1864711 TI - Retrograde ureterorenoscopy in the management of ureteral calculi. AB - Endourologic techniques have revolutionized the line of treatment of ureteral stones. The scope of open ureterolithotomy has been narrowed and the contraindications for endoscopic manipulations of ureteric stones became limited. Using the rigid ureterorenoscope (URS) after endoscopic dilatation of the intramural ureter, we have manipulated 45 ureteral stones located at different levels, 33 in the lower ureter (distal ureter), 7 in the middle third and 5 in the upper third (proximal ureter). Successful manipulations occurred in 32 stones (in 21 by retrieval and in 11 by disintegration using ultrasonic lithotripsy). Failures were due to upward dislodgement of the stone in 5 cases, to grasp or disintegrate the stone in 2, perforation of the ureter in 2, bleeding from the ureteral wall in 2 cases, to reintroduce guidewire in the ureter and to non passable stricture below the stone in 1 case each. Delayed complications occurred in 4 patients. Two patients developed ureteral stricture, one suffered vesicoureteral reflux and one ultimately had urethral stricture. PMID- 1864712 TI - Comparison of 3-day versus 14-day treatment of lower urinary tract infection in children. AB - A total of 87 children were treated for lower urinary tract infection. The infection site was determined on the basis of symptoms and laboratory findings. The patients were assigned to four groups, medicated for 3 and for 14 days with nitrofurantoin or cotrimazole. Results from the short and long-term therapies have not shown any significant differences: 9 out of 43 patients in the 3-day therapy group and 8 out of 44 in the 14-day group presented recurrences within one month. PMID- 1864713 TI - Functional electrical stimulation in the management of incontinence: studies of urodynamics. AB - Intermittent functional electrical stimulation (FES) was employed for the control of incontinence. One FES session lasted for 30 minutes. It was repeated at intervals of 3 days to 1 week via an anal plug electrode. The success rate was 64% in 41 patients with pollakiuria, urgency and/or urge incontinence, and 43% in 7 patients with stress incontinence. Detrusor activity measured by cystometry did not correlate significantly with the effect on subjective symptoms and the urethral pressure did not increase. The remarkable clinical effect was observed in patients with overactive detrusor function. It seems that FES indirectly inhibits detrusor contraction by suppressing the intrasacral pathway for detrusor activity. PMID- 1864714 TI - Metastasis to the penis. Case reports and review of the literature. AB - Metastasis to the penis is rare, despite rich vascularization and complex circulation. Less than 200 cases have been reported. Three new cases of penis metastasis from primary tumours in the bladder and prostate, respectively, are described. The most common symptoms are penile induration and swelling. Treatments, all of which must be considered merely palliative, consist of local tumour excision, radiation therapy, cytostatic and hormone therapy, possibly with partial or total penis amputation. The prognosis is poor, irrespective of the therapy and site of the primary tumour. More than 80% of the patients die within six months after the occurrence of penis metastasis, as a result of disseminated cancer disease. PMID- 1864715 TI - Comparison of the effects of surgical and autologous fascial suture materials on testicular histology in rats subjected to orchiopexy. AB - In this study orchiopexy was performed in 30 Sprague-Dawley rats in order to compare traumatic effects of surgical and autologous fascial suture materials on testicular histology. Abscess formation was observed in 72.7% of the chromic, in 36.3% of the nylon, and in 18.1% of the vicryl fixed groups. There were no abscess formations in the dartos and autologous fascial fixed group. Examination of the testes revealed complete absence of spermatogenesis in the chromic fixed group. Spermatogenesis was normal, 72% in the vicryl, 18.1% in the nylon, 90.9% in the dartos and autologous fascial suture fixed groups. Antisperm antibody was not observed in any rat sera. We consider that it is preferred to use dartos pouch fixation. If necessary, it is advisable to use autologous fascial suture materials. PMID- 1864716 TI - Sclerosing peritonitis caused by disinfectant in a patient under peritoneal dialysis. AB - An uraemic patient under intermittent peritoneal dialysis was found in the 9th month of treatment to present ultrafiltration drop and increase of low-molecular weight substances. Two instances of laparotomy for heavy abdominal bleeding revealed peritoneal thickening, laminar intestinal concrescence and diffuse haemorrhage. The patient died in the 13th month of treatment under symptoms of ileus. Other reasons excluded, sclerosing peritonitis was attributed to the formalin solution employed as disinfectant for the abdominal catheter. The causative factors are listed together with the chances of prevention. PMID- 1864717 TI - Induced priapism and its management. AB - The authors present the seamy side of the beneficial practice to handle erectile impotence with papaverine or with the papaverine-Regitin combination. Attention is called to danger. The various forms of priapism are defined. In connection with 72 cases of priapism the attained results and the way to stop the priapic condition are described. PMID- 1864718 TI - Acute suppurative renal inflammation. AB - Diagnostic and therapeutic aspects of acute suppurative renal inflammation are discussed in connection with 374 cases. Despite negative X-ray and laboratory findings, patients were submitted to operative exploration and 27% of them revealed subcapsular abscesses. Anamnestic facts (fever, shiver, etc.) and closely observed progression in the patient's morbid condition are factors to indicate surgery. Better results from the second part of the observation period (1981-1989) are due partly to better timing of the surgical intervention, partly to modern, highly effective chemotherapy. The mortality rate of acute suppurative renal inflammation dropped from 11 to 3.5%. PMID- 1864719 TI - Relatedness of the nucleotide sequence of the 3'-terminal region of clover yellow vein potyvirus RNA to bean yellow mosaic potyvirus RNA. AB - The sequence of the 3'-terminal 1,357 nucleotides of clover yellow vein potyvirus RNA was determined. A coat protein gene was identified and its predicted amino acid sequence deduced. It had 273 residues with a molecular weight of 31,019. The amino acid and nucleotide sequences of the virus were compared with those of five other potyviruses. The homology between these viruses indicated that clover yellow vein virus was a distinct virus, but had a closer affinity to bean yellow mosaic virus than to the four other potyviruses. PMID- 1864720 TI - Identification of the coat protein gene of bean golden mosaic geminivirus. AB - An open-reading frame designated 1R1, on DNA component 1 of bean golden mosaic geminivirus (BGMV), has been identified as the coat protein gene. A DraI restriction fragment of BGMV DNA1 that includes 1R1 was inserted into the SmaI pKK223-3 expression vector. The 32 kD protein expressed in Escherichia coli cells reacted with antibodies to the BGMV capsid polypeptide and behaved identically to purified capsid protein in western blots. PMID- 1864721 TI - A response to Papa Ola Lokahi (POL). PMID- 1864722 TI - Anisakiasis in Hawaii: a radiological diagnosis. AB - Human anisakiasis, an increasing medical problem in Japan, was recently identified in 7 people in Hawaii. We report an 8th case occurring in an individual who had consumed a large amount of raw squid sushi at a restaurant. The diagnosis of anisakiasis in this patient was made after the parasite was identified by X-ray. To our knowledge, radiographic demonstration of the anisakiasis parasite has not been reported in Hawaii previously. PMID- 1864723 TI - Sarcoidosis: a Hawaii rarity. AB - Sarcoidosis is so rarely seen in residents of Hawaii that it may not be considered as a diagnostic possibility. The differential diagnosis is more complex in Hawaii due to the presence of granulomatous diseases such as tuberculosis and leprosy. We present the first known case of sarcoidosis in a Hawaii resident together with an overview of the disorder. PMID- 1864724 TI - Health Devices. Cumulative index: volumes 11-19. May 1991. PMID- 1864725 TI - Newer approaches to the radiolabeling of monoclonal antibodies by use of metal chelates. AB - Monoclonal antibodies (mAbs) radiolabeled by use of metal chelators are being investigated in the laboratory for use in clinical trials. 111In is presently employed for diagnostic scintigraphy, but its applications are limited by substantive and persistant uptake of radiometal in the liver. Much current research is focused on performing cancer therapy with 90Y and 212Bi chelate linked mAbs. This report chronicles the development and evaluation of chelating agents for 111In-radioimmunoimaging and 90Y- and 212Bi-radioimmunotherapy. PMID- 1864726 TI - Potential artifact for the increase of tumor associated antigens in serum samples from patients injected with monoclonal antibodies. AB - The administration of [131I]B72.3 MAb for both diagnostic and therapeutic purposes is followed by the development of human anti-mouse antibodies (HAMA) in approx. 70% of patients receiving i.v. doses of MAb above 1 mg. The presence of HAMA in circulation interferes in the detection of the tumor-associated glycoprotein TAG-72 using the CA 72-4 RIA. We have reported elsewhere (Ferroni et al., 1990) that heat treatment at 90 degrees C, pH 6.5, for 15 min is capable of precipitating and/or inactivating HAMA without causing any significant loss in antigen recovery. Furthermore, the removal of the interfering activity leads to a more correct evaluation of TAG-72 serum levels in HAMA-positive serum samples and to a continued use of TAG-72 in the follow-up of patients undergoing MAb-based clinical protocols. PMID- 1864727 TI - Comparative biodistribution studies of DTPA-derivative bifunctional chelates for radiometal labeled monoclonal antibodies. AB - Biodistribution of five different backbone-substituted derivatives of SCN-Bz-DTPA (1B4M-DTPA, 1M3B-DTPA, 1B3M-DTPA, GEM-DTPA and 2B-DTPA) linked to MAb B72.3 were compared to that of the parent molecule after labeling with 111indium. Athymic mice, bearing human colon carcinoma xenografts (LS-174T) were injected i.v. to determine the biodistribution of the MAb chelate conjugates. Three of the MAb metal chelate conjugates (1B4M-DTPA, 1M3B-DTPA, and 1B3M-DTPA), labeled with 111In showed efficient and stable tumor localization as well as a slower blood clearance rate than SCN-Bz-DTPA, GEM-DTPA or 2B-DTPA MAb chelate conjugates. Major differences were also seen in normal organ uptake, especially liver and spleen. Tumor-to-liver ratios rose as a function of time for 1B4M-DTPA, 1M3B-DTPA and 1B3M-DTPA MAb chelate conjugates with virtually no accumulation of the radiometal into this organ, as revealed by no increase in the liver-to-blood values. Small accretion in normal liver was noted for SCN-Bz-DTPA, GEM-DTPA or 2B DTPA MAb chelate conjugates. The results reviewed here, and described previously (Roselli et al., 1991) demonstrate that the use in vivo of backbone-substituted forms of the SCN-Bz-DTPA, such as 1B4M-DTPA, 1M3B-DTPA, and 1B3M-DTPA bound to MAbs, can reduce uptake of indium to normal organs while maximizing the dose to tumor. PMID- 1864728 TI - In vivo and in vitro clinical applications of monoclonal antibodies against TAG 72. AB - Monoclonal antibodies against a tumor-associated antigen (TAG-72) with mucin-like properties have been generated. MAb B72.3 was used to identify and help characterize this antigen. B72.3 has been successfully used for the localization of tumor metastases in situ after i.v. administration. MAb B72.3 has also been used in conjunction with CC49, another anti-TAG-72 MAb, to measure TAG-72 levels in sera and effusions. TAG-72 can be found in the fluids of patients with adenocarcinomas from many different sites. This CA 72-4 double determinant radioimmunoassay in conjunction with assays for carcinoembryonic antigen can identify patients with malignancies with greater sensitivity than either assay alone. PMID- 1864729 TI - Preclinical pharmacokinetics and localization studies of the radioiodinated anti ovarian carcinoma MAb MOv18. AB - The in vivo behavior of the monoclonal antibody (MAb) MOv18, with a restricted specificity for human ovarian carcinoma was analyzed on normal and tumor-bearing animals. The pharmacokinetics of the iodine-labeled MAb carried out in BALB/c mice fits an open two-compartment model. The t1/2 alpha was found not to be influenced by the different iodine isotopes used (125I vs 131I) and by the time between labeling procedures and administration. The t1/2 beta were found to be longer after i.p. than i.v. administration and influenced by the time lapse between preparation and administration. A radiolocalization study was carried out in CD1 nu/nu mice bearing i.p. xenotransplant of the human ovarian carcinoma cell line IGROV1. Tumor/non tumor ratios were higher when the time between administration and sacrifice was short and, for 131I-MOv18, with a short interval between labeling and injection. Even if longer half lives were obtained using 125I-MOv18 and i.p. administration a fairly rapid decrease in the values of the percentage of the injected dose per gram of tumor during the time was noted. These data indicate that this MAb could be considered a good candidate for radiotherapeutic approaches. PMID- 1864730 TI - Diagnostic evaluation of 111In and 99mTc radiolabelled monoclonal antibodies in ovarian and colorectal cancer: correlations with surgery. AB - The results of radioimmunoscintigraphy, RIS, in colorectal and gynaecological cancers were related to the surgical findings and the analysis of the surgical specimens. The improvement in the accuracy of RIS with the progression from 111In through 123I to 99mTc as radiolabel is demonstrated. The convenience, low cost and low radiation dose of 99mTc-labelled antibodies brings the technique of RIS into routine use in the management of patients with these cancers. PMID- 1864731 TI - New concepts in monoclonal antibody based radioimmunodiagnosis and radioimmunotherapy of carcinoma. AB - It is now generally agreed that while numerous monoclonal antibodies (MAbs) have been shown to efficiently target tumors in patients, much still needs to be accomplished to optimize MAb based tumor targeting and the use of MAbs in the therapy of human carcinoma. This article will review some recent studies undertaken in our laboratory in an attempt to generate novel recombinant constructs and test new principles to aid in optimizing MAb based diagnosis and therapy. Three areas will be covered: (a) the analysis of dose fractionation protocols; (b) the generation of recombinant/chimeric (rec/chi) MAbs including the generation of a single chain antigen binding protein (SCA); and (c) the use of recombinant interferons (rec IFNs) to selectively up-regulate tumor antigen expression. Each of these topics has been previously described in detail and appropriate references to these articles are included. PMID- 1864732 TI - [Does sonography help in the diagnosis of appendicitis?]. AB - The aim of the presented study was to find whether improvement has ultrasonography in the diagnosis of acute appendicitis and on surgeon's decision referring to laparotomy. 111 patients entering into the emergency station with suspected appendicitis were evaluated in a prospective clinical study. Surgeon and radiologist had to commit themselves to the diagnosis, afterwards signs were discussed. In 32% the appendix was well seen (accuracy 80%), in 27% sonographic examination was doubtful (accuracy 70%) and in 41% the appendix could not be demonstrated. Diameter of normal appendix was 8 mm compared to inflamed appendix with 12 mm (p less than 0.05). The negative laparotomy decreased from 16% to 12.7%. Surgeon was not influenced by sonography in 75%. In 12% ultrasonography decided for laparotomy and in 4.5% sonography prevented operation. We conclude from our results, that sonography reduces negative laparotomy rate. Especially ultrasonography is useful in doubtful clinical pictures. PMID- 1864733 TI - [Consequences of interventional sonography for abdominal surgery]. AB - The sonographic-radiologically guided puncture and catheter insertion enables certain palliative and curative therapeutic procedures to be performed. Liver abscesses represent the most common examples for this procedure, although interabdominal abscesses as well as pancreatic pseudocysts can also be treated successfully. In our collection of clinical cases various preformed pigtail catheters were employed using either the Seldinger-principle or, with help of a rigid needle, introduced directly into the lesion. Advantages of sonographically guided therapeutic interventions include quick implementation without radiation exposure, immediate recognition of possible complications as well as negligible expenditures. Ultrasonically guided therapeutic interventions should be undertaken only through the close collaboration between intervening radiologists and abdominal surgeons. Only so are they both low-risk and successful. PMID- 1864734 TI - [Ultrasound controlled aspiration cytology of liver, bile ducts and pancreas]. AB - Aspiration cytology is an effective and safe method for diagnosis of intraabdominal malignancies. In a prospective study we analysed the cytology in 84 patients. The results showed a sensitivity of 95% with an accuracy of 96%. No false positive diagnosis was found where open biopsy was possible. The aspiration cytology is a good method to decide whether endoscopic stents or embolization of the liver can be used without explorative laparotomy. PMID- 1864735 TI - [Percutaneous pancreatic pseudocyst drainage: a combined sonographic-endoscopic procedure]. AB - Certain pancreas-pseudocysts can be effectively drained either transgastrically or transduodenally using endoscopic procedures. Applicable methods include repeated fine needle punctures, insertion of a drainage tube or the percutaneous pseudocyst-drainage according to Hancke. The percutaneous sonographic pancreas pseudocyst drainage represents an alternative or an adjunct to the classical surgical cyst drainage employing a cysto-jejunostomy or cysto-gastrostomy. The indications are analog to the surgical cysto-enterostomy, whereas the optimal method for each individual patient should be decided by interdisciplinary consultation. The following report presents 21 case studies of pancreas pseudocysts which were treated conservatively using ultrasonographical procedures. PMID- 1864736 TI - [Endoluminal sonography--preoperative staging of rectal cancer]. AB - The endoluminal sonography is a new investigation in staging rectal cancer. In a prospective series the value of the endoluminal sonography is compared with clinical staging and computed tomography. The accuracy in clinical staging, computed tomography and endoluminal sonography was 77%, 76% and 87%, respectively. The reasons for under- and overstaging and the interpretation of perirectal lymph nodes are discussed. The endoluminal sonography is an important new method evaluating the operative procedure of cancers in the lower rectum. PMID- 1864737 TI - [Ambulatory proctologic surgery]. AB - Outpatient surgical proctology is nowadays more and more frequently performed. Between 1986 and 1989, 65% of 1149 anal surgical procedures were performed in our institution on an outpatient basis. The various criteria used to select patients fit for ambulatory surgery seemed adequate, as no complications were observed and no patient required secondary hospitalization. PMID- 1864738 TI - Conversion operation Billroth II into Billroth I with jejunal interposition. AB - First, under consideration of the erroneous operative often techniques often found in patients with B II gastrectomy, all functional complaints of these patients should prompt the consultant to recommend conversion surgery. Secondly, all recurrent ulcerations, whether peptic or anastomositis, represent an indication for conversion surgery. Last but not least reconstruction of normal nutrition passage in an important indication for surgery in patients with B II gastrectomy, restoring near physiologic passage circumstances. Particularly grave in its consequences is the gastric stump carcinoma with its fateful and irrevocable course for patients with B II gastrectomy if regular gastroscopic and laboratory follow-up inspection do not take place (regardless of questionable operation indication). We recall a tragic case of a woman with B II gastrectomy who refused conversion surgery despite histologic verification of metaplasia, who died of gastric stump carcinoma a year later. PMID- 1864739 TI - [Electron microscopy of the exocrine pancreas in experimental acute hypercalcemia]. AB - Hypercalcemia has been associated with acute pancreatitis clinically and in the experimental animal. We studied the pancreatic ultrastructure in acute experimental hypercalcemia. Anesthetized cats (Pentobarbital, 0.55 mg/kg) received Ca++ (Calcium-Gluconate: 0.6 mmol/kgh; n = 4), K+ (KCl: 1.1 mmol/kgh; n = 4) or NaCl (0.9%; n = 4) locally through retrograde infusion into the splenic artery. Biopsies for electron microscopy (EM) were taken at three hours. Eight cats received intravenous Ca++ (0.6 mmol/kgh, 0.3 mmol/kgh after three hours) or NaCl (0.9%) for 12 hours. Biopsies were collected in two animals in three-hour intervals, and in all animals at twelve hours. After local calcium infusion necrotizing pancreatitis was seen macroscopically in the body of the pancreas. Biopsies for EM showed acinar cell necrosis, hydrops of nuclei and mitochondria and needle-like precipitates in the cytoplasma in the center of calcium perfusion. Biopsies taken from the peripheral region of the macroscopically altered tissue revealed desorganisation of the acinar polarisation and the endoplasmic reticulum, with zymogen granules appearing in the basolateral cell portion. After intravenous calcium administration no macroscopical changes were seen. In EM acinar cells showed dilatation and proliferation of the golgi apparatus and increased number of condensing vacuoles indicating stimulation. Again, disorganisation of acinar cell polarisation was present. Control animals treated with K+ or NaCl showed normal pancreatic ultrastructure. The morphological changes after calcium infusion indicate direct damage to the acinar cell. Our results suggest that hypercalcemia induced pancreatitis could originate in the acinar cell. PMID- 1864740 TI - [Intraperitoneal hepatocyte transplantation: morphologic findings and clinical relevance]. AB - In order to evaluate if intraperitoneal hepatocyte transplantation could include a therapeutic approach in acute hepatic failure, isolated hepatocytes as well as microcarrier attached hepatocytes were transplanted intraperitoneally and the survival rates of transplanted cells were evaluated morphologically. The histological investigations showed, that the transplanted hepatocytes undergo complete cell necrosis within 3 days due to a lack of substrate, which also cannot be avoided by an attachment to microcarriers. Liver cell necrosis is followed by a peritoneal reaction resulting in granuloma formation. Because liver cell necrosis occurred early after i.p. hepatocyte transplantation a functional support in acute hepatic failure cannot be expected. PMID- 1864741 TI - [Does tissue pH measurement quantify circulation in the transplanted bronchus in lung transplantation]. AB - Ischemia of the airway is the main cause of severe complications in lung transplantation. Tissue-pH is used as an indicator of ischemia in the myocardium and various other tissues. We developed a pH needle probe which can be applied through a bronchoscope to enable repeated measurements of the pH in the bronchus mucosa. In 8 conditioned mongrel dogs (20-25 kg) an autotransplant of a 4-ring segment of the thoracic trachea was performed and wrapped with an omental pedicle flap in 4 of them (omentum group vs control group). PH-measurements of the mucosa were performed at 3 points of the circumference of the normal trachea as well as the transplant. The measurements were done immediately postoperative and at day 3, 8, 14 and 20 using a modified MI 506 pH-needle electrode with an Ag-AgCl skin reference electrode and a Fisher accumet pH-meter (model 910). After 3 weeks or at occurrence of a severe tracheal stenosis macroscopic and histologic examination of the trachea was done. All animals in the omentum group finished the study. One developed severe stenosis due to tracheal malacia. Three of the four control-dogs had a severe tracheal stenosis at day 12, 13 and 16 which necessitated termination of the experiment. The pH-difference between trachea and transplant immediately postoperative was 0.16 +/- 0.02 in the 4 dogs with healed transplants and 0.15 + 0.03 in the 4 dogs with stenosis due to chondromalacia. Follow-up measurements at day 3 and 8 showed a pH-difference of 0.2 for the group with chondromalacia vs. 0.1 for the healed tracheas (not significant).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864742 TI - [Prevention of pulmonary embolism with the Gunther filter]. AB - From 1987 to 1989 a Gunther vena caval filter was implanted in the inferior caval vein in 37 patients to prevent pulmonary embolism. 20 patients had already suffered from lung emboli and full anticoagulation did not prevent reembolization (11) or was contra-indicated because of hemorrhagic complications (5) or recent operation (4). 17 patients had developed severe deep venous thrombosis with a free ending thrombus (15) as shown by phlebography and in 2 other patients of old age prophylaxis seemed indicated to prevent migration of the thrombi. This device can be inserted percutaneously via a 10-French introduction system. No local complications were observed. 3 patients showed an oedema of a leg 2 to 7 days after insertion with spontaneous regression. One patient had the filter 12 days after implantation completely obstructed by a new embolus that needed to be removed surgically. One patient had an acute caval obstruction 1 1/2 years after implantation. it could not be determined if this was due to new embolisation or to thrombosis of the filter. No pulmonary reembolization was observed. Even if long-term results with the Gunther vena caval filter can not be reported yet, it seems to be a satisfactory device for preventing pulmonary embolism. PMID- 1864743 TI - [Simultaneous coronary and vascular surgery interventions: indications,technique and results]. AB - Atherosclerosis is often a generalized disease, affecting not only coronary circulation, but other parts of vascular system as well. Vascular diseases most commonly encountered in patients with coronary atherosclerosis are carotid disease, abdominal aortic aneurysm and obliterative atherosclerosis in aortoiliac segment. In such situation two options are available: to treat the more significant, life-threatening manifestation first and postpone the other operation--staged approach; or to perform coronary artery bypass grafting (CABG) and other vascular procedures during one single operation--synchronous surgery. The advantages of this latter approach are obvious: patient has to undergo only one operation; there is no additional risk in the waiting period for second operation; surgical treatment is greatly accelerated. From 1978 until July 1990 a total of 123 synchronous CABG and vascular procedures were carried out in our clinic. In the same period, CABG was performed in 3867 pts in the same institution; combined procedures amount to 3.5% of all coronary revascularisations performed in the same period. CABG was done together with carotid endarterectomy (CEA) in 45 pts, associated with resection of abdominal aortic aneurysm (AAA) in 31 and in 28 pts it was combined with vascular procedures in aorto-iliac or femoral segment. In 4 pts a triple procedure--CABG, CEA and peripheral vascular reconstruction--were undertaken. Thoracic aortic aneurysm and CABG were performed in 15 pts. CEA is performed immediately prior to CABG in symptomatic carotid disease, past history of transient ischemic attack, severe bilateral carotid disease and unilateral carotid obstruction with contralateral stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864744 TI - [A method of surgical treatment of complicated varicose veins]. PMID- 1864745 TI - [Injuries of the lower extremity with vascular lesions of the popliteal area. Management errors]. AB - Lower extreemity injury complicated by limb-threatening vascular injuries of the popliteal artery present an infrequent but difficult management problem. In a retrospective study 37 consecutive patients with severely injured lower extremities after blunt trauma, all complicated by popliteal vascular injury, were evaluated. In 10 patients we found severe management errors: In 7 patients a delay in diagnosis of the vascular injury, in 3 patients with extensive bone and soft-tissue damage an inadequate stabilisation of the fracture. The optimal management of complex injury with associated vascular injuries requires a high index of suspicion and a treatment of all components of such an injury. The initial goals are the accurate diagnosis or exclusion of arterial injury, surgical debridement, adequate bony stabilization with minimal additional bone and soft-tissue trauma, revascularisation by interposition of a vein graft after resection of the damaged segment, immediate fascial decompression and early soft tissue reconstruction. PMID- 1864746 TI - [Results of in situ bypass]. AB - The "in situ" bypass technique was adopted by our group in 1986. A total of 53 "in situ" bypasses were carried out until June 1989. The worst symptoms were incapacitating claudication, rest pain or ischemic necrosis, each in about one third of the patients. The site of the distal anastomosis was the popliteal artery below the knee in 40 instances, the peroneal artery in 7 and other infrapopliteal vessels in 6. Valve incisions were performed uneventfully with reusable instruments featuring a sharp-edged blade and an indicator for rotation control of the blade ("Insitutom RC"). Vein branches were located mostly by angiography, but residual arteriovenous fistula remained a vexing problem. In the beginning they were ligated under local anaesthesia. Later on they were dealt with successfully using transluminal embolization. Patients were last examined in July 1990 when the follow-up time ranged from 12 to 51 months. 4 patients had died and 5 were lost to follow-up. Patency rates were evaluated according to the life-table method. They were gratifying for femoro-popliteal bypasses with 87 percent after one year and 83 percent after two and three years. Femoro-tibial peroneal bypasses performed below average, but their number was too small to draw conclusions. PMID- 1864747 TI - [Simultaneous revascularization of the renal arteries in conjunction with reconstruction of aneurysms of the abdominal aorta]. AB - Simultaneous revascularization of stenosed renal arteries during resection of aneurysms of the abdominal aorta was performed in a consecutive series of 30 patients (mean age: 65 +/- 7 years; men 27 [90%]; women 3 [10%]). Right renal artery was operated upon in 20/30 cases (66%) and left renal artery in 15/30 cases (50%) for a mean degree of stenosis of 79 +/- 19%. Suprarenal extension of the aneurysm of the abdominal aorta was observed in 7/30 cases (23%). Emergency operation because of rupture of the aneurysm was necessary in 7/30 cases (23%). The following procedures were performed upon the renal arteries, either isolated or combined, in addition to resection of the aneurysm of the abdominal aorta: reimplantation of the renal artery in 15 cases, thrombendarteriectomy of the renal artery in 11 cases, patchangioplasty in 8 cases, bypass in 4 cases, dilatation in 1 case, autotransplantation in 1 case. The 30-day mortality was 1/23 (4%) for elective procedures versus 3/7 (43%) for emergency procedures (ruptures). Systolic (diastolic) blood pressure dropped from a preoperative mean value of 181 +/- 139 (104 +/- 18) mm Hg to a postoperative mean value of 147 +/- 18 (80 +/- 18) mm Hg: p less than 0.05 (p less than 0.05). Hence, simultaneous revascularization of stenosed renal arteries during resection of aneurysms of the abdominal aorta helps not only to salvage renal parenchyma but also to control the risk factor hypertonia in a significant number of patients. PMID- 1864748 TI - [Results of surgical treatment of ischemic colitis]. AB - Between January 1984 and December 1989, 13 patients, aged 39 to 89 (median 63), underwent surgery for histologically proven ischemic colitis. Most suffered from pre-existing cardiovascular conditions (2 shortly after surgery for aortic aneurysm). One patient developed ischemia after the traumatic avulsion of the ileocolic artery and another after the spontaneous reduction of a strangled inguinal hernia. Diagnosis of ischemic colitis was made prior to operation in 4 instances only. The left colon was affected 5 times and the right colon 8 times (with the terminal coil of ileum 3 times). Treatment always consisted in segmental colectomy; laparotomy was used in 3 patients (2 to 7 reoperations). Colon anastomosis was performed directly 5 times, while 4 patients had secondary stomy closures; 2 patients still have their original stomy. Two patients died (15%), one of sepsis and the other following broncho-aspiration. The prognosis of ischemic colitis is rather favorable, even at the stage of transmural necrosis, provided all ischemic zones are resected. This is in contrast with the severe mortality of mesenteric infarcts, when extensive small bowel necrosis is found in association with colonic ischemia. PMID- 1864749 TI - [Incidence of primary mediastinal lesions: change in the profile and therapeutic implications]. AB - The pattern of occurrence of mediastinal masses has to be taken into account when treating and approaching these lesions. In most reported series tumors of neural or germinal origin and thymomas are predominant. We reviewed the records of 277 patients operated for primary mediastinal lesions over the last 25 years (1965 1989) in our center. Surprisingly (Hodgkin's and non-Hodgkin's) lymphomas (24 25%) were found to emerge as the most common tumors in our series, whereas tumor of neural (11%) and germinal (65%) origins were relatively rare and decreasing in incidence. Thymomas (17%) and mediastinal cysts (14%) occurred as predicted in the literature. Consequently the malignancy rate was high (53%) even in asymptomatic patients (18%). Similar findings have been described recently by others. Factors responsible for this new distribution are difficult to identify. The therapeutic implications of the changes are discussed. PMID- 1864750 TI - [Significance of rib fractures in simple and multiple trauma]. AB - In a retrospect study we evaluated the clinical impact of traumatic rib fractures. Our series included 96 patients treated between 1986 and 1988. Haemato and/or pneumothorax corresponded closely to the number of fractured ribs. There was a highly significant association (p less than 0.001) between the number of fractured ribs and polytrauma. The leading cause of injuries was a traffic accident. PMID- 1864751 TI - [Functional results of Neer II type hemi-arthroplasty joint replacement of multi fragment humerus head fractures]. AB - Among the fractures of the proximal humerus--a typical kind of injury affecting elderly people, as well as gainfully employed patients, the comminuted and dislocated humeral head fractures have a specific position because of therapeutical reasons. By means of a retrospective analysis, a review is given of the results of 26 comminuted humeral head fractures type IV-VI according to Neer, treated with a Neer prosthesis type II at the surgical clinic of the Kantonsspital Lucerne between 1983 and 1989. Our interest is mainly concentrated on the functional results and on their correlation with biomechanical and perioperative factors. We use the fracture-classification and functional evaluation as described by Neer. For the results classified as "failures" (13 cases) the functional deficits of the glenohumeral joint mobility are essential. The scores reveal no significant correlation to the age of the patients, to the time interval between trauma and operation, as well to the duration of the postoperative physiotherapy. On the other hand the scores of patients with preoperative manipulation of the fractured joint (i.e. osteosynthesis, reduction attempts, physiotherapy) were significantly worse than those with primary prosthetic replacement. Furthermore, because of the insufficient restitution of the lever arm conditions, the implantation of the small-head component (15 mm) leads to significantly less favorable functional scores, with a corresponding radiological hyperpression in the cranial articular space. Our analysis leads to the following conclusions: 1. Under the condition of a conclusive preoperative diagnosis a primary prosthetic procedure is recommended depending on the type of fracture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864752 TI - [Surgical treatment of acromioclavicular joint injury]. AB - The acromioclavicular joint plate according to Rahmanzadeh allows the safe retention of the reset acromioclavicular joint in stage Tossy III and in exceptional cases also in stage Tossy II traumata when simultaneous early functional post-treatment is done from the first postoperative day on. The clinical results obtained after follow-up examinations of 53 of the 83 patients treated in this way were mostly good or very good. Perfect radiological results were obtained in 50% of these patients; 40% showed a slight subluxation and 10% a marked but pain-free subluxation. PMID- 1864753 TI - [Follow-up results of osteosynthesis of medial femoral neck fractures with the dynamic hip screw]. AB - The operative treatment of subcapital femoral neck fractures of stages Garden III and IV in the young patient is still a problem. The current methods of osteosynthesis show a high rate of avascular necrosis of the femoral head. We controlled 24 patients with subcapital femoral neck fracture, who were treated with a dynamic hip screw (DHS). The average age of these patients is 55 years. They were examined after 30-89 months from the operation. All patients were assessed regarding clinical and radiological parameters. All of the six patients with femoral neck fractures of stages Garden I and II had no pain, their clinical results were good. In one of these patients we found a partial avascular necrosis of the femoral head. Four out of the 18 patients with femoral neck fractures of stages Garden III and IV had painful complications, 3 of them needed a reoperation. Fourteen patients of the group with femoral neck fractures of stages Garden III and IV had no pain and wer satisfied with the result. But in this group we found 7 patients with partial avascular necrosis of the femoral head. These results are discussed and compared with data published elsewhere. PMID- 1864754 TI - [6 years experiences with the "dynamic condylar screw" in supra- and intercondylar fractures]. AB - 44 supra- and intercondylar fractures were treated with the "Dynamic Condylar Screw" (DCS). Our experience with this device in a teaching hospital with surgeons of different training levels was encouraging, since there was no complication due to the insertion technique in this complex fracture setting. When we compare our results obtained with the DCS with those in the literature achieved with the angled blade plate, we got the same or better results in respect to implant failure, infection, fracture healing and function. PMID- 1864755 TI - [Interlocking intramedullary nailing of the femur: is the advantage of early mobilization gained by risking a malposition?]. AB - We report a follow-up of 57 consecutive femoral fractures treated by internal fixation with the AO Universal Interlocking Nall. All fractures (91% follow-up) had healed within a mean of 22 months (range 9-50) after operation. Full weight bearing was possible after an average of 9 weeks (range 2-20). The only infection occurred after a secondary open lengthening osteotomy. In 5 cases a rotational malposition or length discrepancy had to be corrected shortly after initial surgery. Rotational malposition in excess of 10 degrees occurred in 26% of cases (mostly external rotation) and length discrepancy exceeding 1 cm in 13% (mostly shortening). The frequency of malposition is explained by the absence of rotational or length control during operation. We recommend that malposition be correlated without delay by reoperation. PMID- 1864756 TI - [Arthroscopic notch-plasty in persistent extensor deficit following anterior cruciate ligament-plasty]. AB - Occasionally following ACL reconstruction, an extension deficit persists, because of impingement of the transplant in the notch. In six cases an arthroscopic notchplasty was performed, five of these cases were immediately successful. Due to initial insufficient resection of the notch, one patient required a second notchplasty to achieve full extension. PMID- 1864757 TI - [Does partial anterior cruciate ligament rupture really exist?]. AB - From 1983 to 1989 129 partial tears of the anterior cruciate ligament were diagnosed by arthroscopy. To confirm the diagnosis of a partial rupture of the anterior cruciate ligament, we began to split the synovial sheath of the anterior cruciate ligament in 1986 in order to prove the continuity of the fibers. Applying this technique, we quite often found the anterior cruciate ligament completely torn. Hence the rate of partial tears of the anterior cruciate ligament decreased from about 10% of all anterior cruciate ligament ruptures 1983 to about 3% 1989. 42 patients whose diagnosis had been a partial rupture of the anterior cruciate ligament were reviewed clinically to determine whether the anterior cruciate ligament injury had finally proved to be an insignificant lesion or had caused a knee instability. The overall results were very good in 12% and good in 14%; 41% showed a fair, 26% a poor result. Because of this unfavourable outcome, we believe that most of the partial tears of the anterior cruciate ligament should be regarded as complete ruptures. PMID- 1864758 TI - [External fixator as primary and definitive treatment of tibial fracture with severe soft tissue damage]. AB - The initial treatment of choice of fractures with severe soft tissue damage of the leg is the stabilization with an external fixator. After successful healing the question arises whether to continue the initial treatment with the external fixator to bone union or to change the initial concept by an internal fixation. Our experience with 62 fractures of the tibia (follow-up of 59 fractures) from 1985 to 1989 shows that 72% of the fractures were healed by the external fixator alone. Delayed union or pseudoarthrosis occurred in 17% and were mostly treated by late internal fixation. An analysis of the fracture types (new AO classification) did not show certain fracture types, that did not respond to the external fixator treatment alone. We conclude that the reason for a delayed union or pseudoarthrosis is less a morphological than a biological one. We recommend the first and final external fixator as treatment for fractures with severe soft tissue damage of the leg. PMID- 1864759 TI - [Talus fracture. Injury pattern, treatment tactics and results of operation (1980 1989)]. AB - The results of 25 operated talus fractures are presented. 7 of these were peripheral fractures with excellent results, 18 central fractures with only satisfying or even bad outcome. Although we didn't see any avascular necrosis of the talus, almost all patients had pain and slight or even severe signs of arthrosis in the ankle or subtalar joint. PMID- 1864760 TI - [Surgical treatment of diabetic malum perforans by ray resection]. AB - The main cause of the diabetic perforating ulcer is peripheral neuro- and angiopathy. Trivial injuries of the foot, wounds (chiropody), bacterial or mycotic infections often lead to tissue defects in the form of a perforating ulcer (in which neuropathy predominates) or of gangrene (in which angiopathy predominates). The deeply penetrating trophic ulcer with secondary development of osteitis in the foot bones often present us with difficult therapeutic decisions. Several measures for its treatment are given in the literature. We report on 5 patients in whom a plantar perforating ulcer was present beneath the 2nd an 3rd metatarsal heads with radiologically confirmed osteitis. The entire ray, including the corresponding toe, is excised as a wedge from the plantar and dorsal aspects, and the wound left open to heal. The indications, the course of healing, the duration of hospital admission and the complications are described. PMID- 1864761 TI - Dose-related sevoflurane metabolism to inorganic fluoride in rabbits. AB - Serum concentrations and urinary excretion of inorganic fluoride (fluoride ion), a metabolite of sevoflurane, were measured by an ion-chromatographic analyzer after inhalation of three different concentrations of sevoflurane in adult, male Japanese white rabbits weighing 2.6-3.6 kg. Sevoflurane was administered at concentrations of 0% (control), 1%, 2% and 3% (Groups I, II, III and IV, respectively) through a sevoflurane vaporizer for 2 hr under controlled ventilation. Blood and urine samples were collected during and after termination of sevoflurane inhalation at scheduled time intervals for 24 hr. The total volume of urine, the urinary pH and the osmolality of serum and urine were not significantly different among any of the groups. Osmolality of the serum and urine was within normal range in all groups of animals. The mean serum peak values of fluoride ion were 0.7 +/- 0.5, 22.8 +/- 8.7, 31.8 +/- 11.0 and 41.5 +/- 13.2 microM (mean +/- SD) in groups I, II, III and IV, respectively. Peak values were recorded within 15 min after the termination of inhalation. The cumulative amounts of fluoride ion excreted in urine in 24 hr were calculated to be 5.0 +/- 1.6, 26.1 +/- 6.7, 41.4 +/- 11.3 and 64.3 +/- 18.0 mumol (mean +/- SD) in groups I, II, III and IV, respectively. Regression analysis revealed significant correlations between the formation and excretion of fluoride ion, and the dose of sevoflurane (r = 0.85, p less than 0.05 and r = 0.89, p less than 0.05, respectively). The authors conclude that the formation and excretion of fluoride ion after sevoflurane anesthesia is dependent on the dose of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864762 TI - Inhibition of 3H-TdR uptake for human gastric carcinoma cells by epidermal growth factor specific antibody. AB - This study examined whether human gastric carcinoma cells produced EGF for self stimulation, using TMK-1 and MKN-28 cells which express mRNA for EGF and EGF receptor. EGF protein production was confirmed by ELISA and flow cytometric analysis. The lysates of these cells replaced EGF-induced biological activity to EGF receptor bearing KB cells but the culture supernatants did not. Furthermore, EGF-radioreceptor assay revealed non-secretion of EGF product. EGF specific monoclonal antibody neutralized exogenous EGF-induced 3H-TdR uptake, and inhibited spontaneous 3H-TdR uptake of TMK-1 and MKN-28 cells. These results suggest that EGF specific antibody binds to EGF protein at the cell surface, leading to the inhibition of 3H-TdR uptake, and that EGF produced by tumor cells may act as an autocrine growth factor in human gastric carcinoma cells. PMID- 1864763 TI - Aerobic dehalogenation of halothane showing different substrate dependency from anaerobic dehalogenation in liver microsomes of guinea pig. AB - The formation of trifluoroacetic acid (TFAA) from halothane under aerobic conditions and that of chlorotrifluoroethane (CTE) and chlorodifluoroethylene (CDE) from halothane under anaerobic conditions were studied using guinea pig liver microsomes. The formation of TFAA was inhibited by specific inhibitors of cytochrome P450 (P450), such as carbon monoxide and metyrapone and was dependent upon P450 contents. The maximum activity of the TFAA formation was obtained at pH 6.0. On the other hand, the maximum activity to form CTE and CDE was obtained at pH 7.4. The formation of TFAA reached a plateau at a halothane concentration above 0.17 mM, but the rate of formation of CDE and CTE was dependent upon a halothane concentration up to 1.5 mM. The values of apparent Michaelis-Menten constant (Km) and maximum velocity (Vmax) for TFAA formation were 0.067 mM and 0.349 nmol/nmol P450/min respectively, those for CDE formation were 0.983 mM and 0.326 nmol/nmol P450/min respectively, and those for CTE formation were 1.71 mM and 0.752 nmol/nmol P450/min respectively. These results showed clearly that the formation of TFAA, CDE and CTE was catalyzed by the P450 system in guinea pig liver microsomes. Under optimal conditions, saturation was observed in the formation of TFAA from halothane at a halothane concentration above 0.17 mM but the formation of CDE and CTE was not saturated at this concentration, and the value of apparent Km for TFAA formation was lower than those for CDE and CTE formation. PMID- 1864764 TI - Study of portal arterialization with auxiliary liver in rats. AB - The effect of portal arterialization was examined in 20 heterotopic auxiliary rat livers. Portal blood was supplied from recipient iliac artery (0.58 mm in diameter) connected to the donor portal vein using the cuff technique. Portal hypertension caused by arterial blood pressure resulted in the immediate operative death by bleeding in four of the rats (20%) from the spontaneous rupture of the graft capsule. Severe graft congestion was noticed at autopsy 3-14 days after transplantation in 13 rats. Massive portal and sinusoidal congestion and focal hemorrhagic necrosis were confirmed by pathological examination. The results of our study demonstrate that the portal arterialization used in the auxiliary rat liver transplantation would not be applicable unless the optimal hemodynamic condition is warranted. PMID- 1864765 TI - Mode of antibacterial action of cefprozil, a new cephalosporin, on Escherichia coli, Serratia marcescens and Morganella morganii. AB - The mode of antibacterial action of cefprozil (CFPZ, BMY-28100), a newly developed cephalosporin, was investigated using Escherichia coli K12, Serratia marcescens IFO 12648 and Morganella morganii IFO 3848 as test organisms, in comparison with the action of cefaclor (CCL). The minimum inhibitory concentrations (MICs) of CFPZ for these organisms were 1.56, 800 and 25 micrograms/ml, whereas those of CCL were 1.56, 800 and 100 micrograms/ml, respectively. The addition of a subinhibitory concentration (1/4 MIC) of ethylenediaminetetraacetic acid (EDTA), which damages the permeability barrier of the outer membrane, markedly reduced the MICs of CFPZ for E. coli and S. marcescens, compared with those of CCL, whereas the MICs of both antibiotics for M. morganii were hardly affected by the presence of EDTA. CFPZ was more stable to beta-lactamase activities from these organisms than CCL. The cross-linking reactions of peptidoglycan synthesis catalyzed by the ether-treated cells from these organisms were inhibited by a lower concentration of CFPZ than of CCL. PMID- 1864766 TI - Establishment and characterization of human medulloblastoma xenograft line. AB - A new xenotransplantable tumor line, MED-FU, was derived from a 6-year-old female patient with cerebellar medulloblastoma. This tumor was grown in nude mice as serially transplantable subcutaneous xenografts composed of small round cells with hyperchromatic nuclei and scant cytoplasm. Many rosettes and mitoses were observed. Immunohistochemically, glial fibrillary acidic protein (GFAP), S-100 protein, and neuron specific enolase (NSE) were not detected. The doubling time of the subcutaneous tumors was 6.8 days. Highly concentrated polyamines were detected in the tumor tissue and serum of tumor-bearing mice. This xenotransplanted tumor line, MED-FU, is considered to provide an available experimental model for the study of human medulloblastoma. PMID- 1864767 TI - WPW syndrome complicated by another cardiac disorder. AB - During the past 28 months, 16 cases of WPW syndrome were operated on at Hiroshima University Hospital. Two cases were complicated by other cardiac disorders which accelerated tachycardia, making diagnosis difficult. One of these cases showed serious mitral regurgitation, due to infective endocarditis and the patient suffered cardiac failure accompanied by paroxysmal tachycardia not responsive to medical therapy or cardioversion. A complex rhythm with atrial fibrillation and antegrade conduction rhythm through the accessory pathway made diagnosis and therapy quite difficult. The condition of the other patient was associated with myocardial bridging which caused angina pectoris during paroxysmal tachycardia. Myocardial scintigraphy showed myocardial ischemia in the antero-lateral area of the left ventricle. In the former case, mitral valve replacement and interruption of the accessory pathway were undergone simultaneously. In the latter case, myotomy of the muscle on segment 7 was conducted, following interruption of the accessory pathway. PMID- 1864768 TI - Effects of several volatile anesthetics on the Ca(2+)-related functions of skinned skeletal muscle fibers from the guinea pig. AB - The effects of various volatile anesthetics on intramuscular Ca(2+)-related functions were studied with the skinned fiber technique in guinea pig skeletal muscles. All the volatile anesthetics tested significantly enhanced Ca(2+) induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) at clinical concentrations with negligible effects both on Ca2+ sensitivity of the contractile system and on Ca2+ uptake by the SR. A comparison was made of the enhancing effect of several volatile anesthetics on CICR at clinical concentrations. Halothane was the most potent, followed by methoxyflurane, isoflurane, enflurane, sevoflurane and diethyl ether. If CICR plays an important role in triggering MH, this order of volatile anesthetics on their enhancing effect on CICR, also corresponds to their potency in triggering MH. PMID- 1864769 TI - Effect of microgravity on the respiratory system. AB - Because the pleural pressure gradient and regional distribution of pulmonary function are gravity dependent, substantial changes may be expected during weightlessness. Although very few measurements have been made during spaceflights, a number of observations during brief periods of weightlessness inside aircraft flying with parabolic trajectories confirm these predictions. Single-breath N2 washouts suggest a marked reduction in the inequality of ventilation distribution seen at 1 G. Similarly, inferences made from cardiogenic oscillations during single-breath washouts suggest a greater uniformity of perfusion during weightlessness. This is supported by changes seen on chest radiographs as well as by more direct measurements of regional blood flow distribution using radioactive iodine-labeled macroaggregates. Vital capacity is only slightly reduced, but functional residual capacity decreases by approximately 10% and maximum expiratory flow rates are slightly decreased, especially at low lung volumes. Weightlessness decreases abdominal girth, increases abdominal compliance, and substantially increases the abdominal contribution to tidal volume during resting breathing. Despite these changes, there does not appear to be any alteration in the temporal pattern of breathing. However, the deposition of inhaled medium-sized aerosol particles is substantially reduced, as predicted by model analyses of gravitational sedimentation. Virtually all these observations describe effects at the very onset of weightlessness. Practically nothing is known of slower functional changes and adaptations to prolonged weightlessness. Systematic repeated measurements during manned spaceflights will hopefully begin to provide some information on this subject in the near future. PMID- 1864770 TI - Muscle hypertrophy response to resistance training in older women. AB - We conducted a 12-wk resistance training program in elderly women [mean age 69 +/ 1.0 (SE) yr] to determine whether increases in muscle strength are associated with changes in cross-sectional fiber area of the vastus lateralis muscle. Twenty seven healthy women were randomly assigned to either a control or exercise group. The program was satisfactorily completed and adequate biopsy material obtained from 6 controls and 13 exercisers. After initial testing of baseline maximal strength, exercisers began a training regimen consisting of seven exercises that stressed primary muscle groups of the lower extremities. No active intervention was prescribed for the controls. Increases in muscle strength of the exercising subjects were significant compared with baseline values (28-115%) in all muscle groups. No significant strength changes were observed in the controls. Cross sectional area of type II muscle fibers significantly increased in the exercisers (20.1 +/- 6.8%, P = 0.02) compared with baseline. In contrast, no significant change in type II fiber area was observed in the controls. No significant changes in type I fiber area were found in either group. We conclude that a program of resistance exercise can be safely carried out by elderly women, such a program significantly increases muscle strength, and such gains are due, at least in part, to muscle hypertrophy. PMID- 1864771 TI - Substrate and hormonal responses to exercise in women using oral contraceptives. AB - Hormone and substrate responses to mild and heavy treadmill exercise were compared in women who used oral contraceptives (OC group; n = 7) and in normally menstruating women (control group; n = 8). Venous blood samples were obtained before exercise (-5 min), during exercise (15, 30, 45, and 60 min), and 30 min after exercise. All samples were analyzed for glucose, lactate, free fatty acids (FFA), glycerol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), human growth hormone (hGH), cortisol, insulin, estradiol (E2), and progesterone (P). Substrate patterns during exercise were not altered by the phase of the menstrual cycle or OC usage. However, in the OC group the FFA concentrations were consistently higher during mild exercise and the glucose concentrations were lower at rest and during exercise than in the control group (P less than 0.05). No differences in lactate or glycerol responses were observed between the groups (P greater than 0.05). The responses of insulin and hGH to exercise were not related to the OC use per se but rather to the steroid status, either endogenous or exogenous. Specifically, during the steroid phases (OC use phase and luteal phase) 1) insulin concentrations were not quite as markedly reduced (i.e., 12% higher when luteal phase and OC usage phase data were combined; P less than 0.05), and 2) hGH concentrations at rest and during light exercise were higher in the OC group during the OC use phase (P less than 0.05). LH patterns were not affected by exercise (P greater than 0.05), but a slight decrease was found in FSH (P less than 0.05). Increments in P and E2 were observed in the control group in both the follicular and luteal phase (P less than 0.05), but much greater increments in P occurred in the luteal phase than in the follicular phase (P less than 0.05). In contrast to the control group, no increments in P, E2, or cortisol occurred in the OC users during exercise (P greater than 0.05). Therefore the new observations in this study are that 1) insulin and growth hormone respond in a complex manner during exercise with either the phase of the menstrual cycle or the phases of OC use and disuse and 2) the steroid concentrations (P, E2, cortisol) are increased in the controls but not in the OC users during exercise. The latter point suggests that normal steroid increments are due to an increased rate of secretion rather than a decrease in the hepatic clearance of these steroids.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1864772 TI - Effects of electric charge on hydraulic conductivity of pulmonary interstitium. AB - The hydraulic conductivity of pulmonary interstitium was measured in a short isolated segment of interstitium surrounding a large pulmonary artery (1-3 mm diam) of the rabbit. The flow rate of the following solutions was measured sequentially: normal saline, polycation protamine sulfate (0.08 mg/ml), cationic dextran (0.1 or 1.5%) or anionic dextran (0.1 or 1.5%), and hyaluronidase (testes, 0.02%) solution. The pH of all solutions was adjusted to 7.35-7.40. The ratios of the flow of protamine sulfate and cationic dextran to that of saline averaged 2.3 +/- 0.92 (SD, n = 7) and 3.0 +/- 1.2 (n = 6), respectively. The anionic dextran-to-saline flow ratio averaged 0.72 +/- 0.28 (n = 13). Flow increased in the presence of positively charged molecules and decreased in the presence of negatively charged molecules. At a lower pH of 5.0-6.0, only 0.1% cationic dextran had an effect on interstitial conductivity. Thus pulmonary interstitium at physiological pH has the properties of a negatively charged membrane. The increased interstitial conductivity caused by the positively charged molecules was not observed after treatment with hyaluronidase. These effects of electric charge on interstitial conductivity were partly attributed to the presence in the interstitium of negatively charged hyaluronan. PMID- 1864773 TI - Muscle structure and performance capacity of Himalayan Sherpas. AB - The ultrastructure of the vastus lateralis muscle of Sherpas from Nepal [5 males; age 28 +/- 2.8 (SD) yr, indirect maximal O2 consumption 48.5 +/- 5.4 ml.kg( 1).min(-1)] was assessed and compared with those of sedentary lowlanders and of Caucasian climbers before and after high-altitude exposure. The mean cross sectional area of the fibers was 3,186 +/- 521 microns2, i.e., similar to those of Caucasian elite high-altitude climbers (3,108 +/- 303 microns2) and a group of climbers after a 6- to 8-wk sojourn at 5,000-8,600 m (3,360 +/- 580 microns2) but significantly (P less than 0.05) smaller than that of unacclimatized climbers (4,170 +/- 710 microns2) and slightly, although not significantly, lower than that of sedentary lowlanders (3,640 +/- 260 microns2). The number of capillaries per square millimeter of muscle cross section was 467 +/- 22, not significantly smaller than those of climbers on return from a Himalayan expedition (538 +/- 89) and elite high-altitude climbers (542 +/- 127) but significantly (P less than 0.05) greater than that of sedentary lowlanders (387 +/- 25). The volume density of mitochondria was 3.96 +/- 0.54%, significantly (P less than 0.05) less than the values found for any other investigated group, including sedentary subjects at sea level (4.74 +/- 0.30%). It is concluded that Sherpas, like acclimatized Caucasian climbers, are characterized by 1) facilitated convective and diffusive muscle O2 flow conditions and 2) a higher maximal O2 consumption-to-mitochondrial volume ratio than lowlanders despite a reduced mitochondrial volume density. PMID- 1864774 TI - Effects of hydrogen sulfide exposure on surface properties of lung surfactant. AB - Hydrogen sulfide is an irritant and chemical asphyxiant gas that exerts its primary toxic effects on the respiratory and neurological systems. Exposure to hydrogen sulfide above a threshold value of 200-300 ppm is characterized by the sudden onset of hemorrhagic pulmonary edema. The purpose of this study was to determine whether this response is associated with changes in the surface properties of pulmonary surfactant. Bronchoalveolar lavage fluid was retrieved from the lungs of Fischer 344 rats exposed to two concentrations of hydrogen sulfide or fresh air for 4 h. Surface tension-lowering properties were assayed using a captive bubble surface tensiometer. Lung injury was assessed by histopathology and measurements of total protein and lactate dehydrogenase activity in the lavagate. Marked abnormalities in surfactant activity were demonstrated in the lavagates from rats exposed to the highest concentration (300 ppm) of hydrogen sulfide. These involved the properties of adsorption to the air water interface and surface tension lowering under quasi-static interfacial compression. Exposure to 200 ppm hydrogen sulfide had no effect on minimum surface tension despite a significant increase in protein and lactate dehydrogenase in the lavagate. This would suggest a threshold-type response for the inhibition of surfactant activity by hydrogen sulfide. In vitro studies using normal rat surfactant showed that the abnormalities in surfactant activity were due to inhibitors in the edema fluid and not to a direct effect of sulfide on surfactant. The pathophysiological consequences of increased alveolar surface tension after hydrogen sulfide exposure may need to be considered in the clinical setting. PMID- 1864775 TI - Renal O2 consumption during progressive hemorrhage. AB - Most mammalian tissues regulate O2 utilization such that O2 consumption (VO2) is relatively constant at O2 delivery (DO2) higher than a critical value (DO2c). We studied the relationship between VO2 and DO2 of kidney and whole body during graded progressive exsanguination. The relationship between whole body VO2 and DO2 was biphasic, and whole body VO2 decreased by 5.6 +/- 14.4% (P = NS) from the initial value to the value nearest whole body DO2c. Kidney DO2 decreased in direct proportion to whole body DO2 such that the average R2 value describing the linear regression of kidney DO2 vs. whole body DO2 was 0.94 +/- 0.02. The relationship between kidney, like whole body, VO2 and DO2 appeared biphasic; however, kidney VO2 decreased by 63.3 +/- 10.4% (P less than 0.0001) from the initial value to the value nearest kidney DO2c. Renal O2 extraction ratio was relatively constant over a wide range of kidney DO2, whereas whole body O2 extraction ratio increased progressively at all whole body DO2 values as whole body DO2 decreased. However, final values of O2 extraction ratio were indistinguishable for whole body (0.86 +/- 0.1) and kidney (0.86 +/- 0.06) (P = NS). We conclude that the pattern of kidney and whole body VO2 response to decreasing DO2 differs during hemorrhage, particularly in the range of DO2 normally associated with tissue wellness. PMID- 1864776 TI - Skeletal muscle metabolism and work capacity: a 31P-NMR study of Andean natives and lowlanders. AB - Two metabolic features of altitude-adapted humans are the maximal O2 consumption (VO2max) paradox (higher work rates following acclimatization without increases in VO2max) and the lactate paradox (progressive reductions in muscle and blood lactate with exercise at increasing altitude). To assess underlying mechanisms, we studied six Andean Quechua Indians in La Raya, Peru (4,200 m) and at low altitude (less than 700 m) immediately upon arrival in Canada. The experimental strategy compared whole-body performance tests and single (calf) muscle work capacities in the Andeans with those in groups of sedentary, power-trained, and endurance-trained lowlanders. We used 31P nuclear magnetic resonance spectroscopy to monitor noninvasively changes in concentrations of phosphocreatine [( PCr]), [Pi], [ATP], [PCr]/[PCr] + creatine ([Cr]), [Pi]/[PCr] + [Cr], and pH in the gastrocnemius muscle of subjects exercising to fatigue. Our results indicate that the Andeans 1) are phenotypically unique with respect to measures of anaerobic and aerobic work capacity, 2) despite significantly lower anaerobic capacities, are capable of calf muscle work rates equal to those of highly trained power- and endurance-trained athletes, and 3) compared with endurance-trained athletes with significantly higher VO2max values and power-trained athletes with similar VO2max values, display, respectively, similar and reduced perturbation of all parameters related to the phosphorylation potential and to measurements of [Pi], [PCr], [ATP], and muscle pH derivable from nuclear magnetic resonance. Because the lactate paradox may be explained on the basis of tighter ATP demand-supplying coupling, we postulate that a similar mechanism may explain 1) the high calf muscle work capacities in the Andeans relative to measures of whole-body work capacity, 2) the VO2max paradox, and 3) anecdotal reports of exceptional work capacities in indigenous altitude natives. PMID- 1864777 TI - Respiratory compliance during sedation, anesthesia, and paralysis in infants and young children. AB - Although total respiratory compliance (Crs) has been shown to fall in adults on induction of halothane anesthesia, no successful paired studies have been reported in children. The multiple occlusion technique was used to measure Crs in 17 infants and young children during sedated sleep (CrsS) and shortly after, following induction of halothane anesthesia (CrsA). Crs fell in all but one infant after induction of anesthesia, with a mean fall of 34.7% (range 0-58%). This was accompanied by a reduction in tidal volume and increase in frequency in every case. In 7 of the 17 children, who were to be paralyzed for surgical purposes, Crs was also measured in this anesthetized-paralyzed state. When tidal volume administered during manual ventilation was similar to that observed during measurement of CrsA, Crs during this low-volume ventilation was similar to CrsA. When tidal volume was increased and Crs remeasured, there was a significant increase in every case, with the high-volume Crs within 10% of CrsS in all but one child, in whom there was a 31.4% increase with respect to CrsS. Changes in tidal volume accounted for approximately 50% of the variability in each state. These results demonstrate a highly significant fall in Crs in infants and young children after induction of halothane anesthesia. In addition it appears that this reduction in Crs can be reversed by paralyzing the child and manually ventilating with tidal volumes approximating those seen during sedation. PMID- 1864778 TI - Oxygen cost of inspiratory loading: resistive vs. elastic. AB - We measured the O2 cost of breathing (VO2resp) against external inspiratory elastic (E) and resistive loads (R) when end-expiratory lung volume, tidal volume, breathing frequency, work rate, and pressure-time product were matched in each of six pairs of runs in six subjects. During E, peak inspiratory mouth pressure was 65.7 +/- 1.8% (SD) of the maximum at functional residual capacity. However, during resistive runs, peak inspiratory mouth pressure was 41.1 +/- 2.8% of the maximum at functional residual capacity. In 36 paired runs, where both work rate and pressure-time product were within 10%, VO2resp for E was less than for R (81 and 96 ml/min, respectively; P less than 0.01). During loaded and unloaded breathing with the same tidal volume, we measured the changes in anteroposterior diameter of the lower rib cage in five subjects. In four subjects we also recorded the electromyograms of several fixator and stabilizing muscles. During E and R, the change in anteroposterior diameter of the lower rib cage was 116 +/- 5 and -45 +/- 4% (SE), respectively, of the unloaded value (P less than 0.01), indicating greater deformation during E. Although the peak electromyographic activity was 72 +/- 16% greater during E (P less than 0.01), there was no difference between the loads for area under the electromyogram time curve (P greater than 0.05). However, the time to 50% peak activity was less during R (P less than 0.02). We conclude that, even when work rate and pressure time product are matched, VO2resp during R is greater than that during E. This difference may be due to preferential recruitment of faster and less efficient muscle fibers. PMID- 1864779 TI - Effects of left atrial pressure on the pulmonary vascular response to hypoxic ventilation. AB - We investigated the effects of hypoxic ventilation on the pulmonary arterial pressure- (P) flow (Q) relationship in an intact canine preparation. Mean pulmonary P-Q coordinates were obtained during hypoxic ventilation and during ventilation with 100% O2 at normal and at increased left atrial pressure. Specifically, we tested the hypothesis that, over a wide range, changes in left atrial pressure would alter the effects of hypoxic ventilation on pulmonary P-Q characteristics. Seven dogs were studied. When left atrial pressure was normal (5 mmHg), the mean value of the extrapolated intercept (PI) of the linear P-Q relationship was 10.9 mmHg and the slope (incremental vascular resistance, IR) of the P-Q relationship was 2.2 mmHg.l-1.min. Hypoxic ventilation increased PI to 18 mmHg (P less than 0.01) but did not affect IR. Subsequently, during ventilation with 100% O2, when left atrial pressure was increased to 14 mmHg by inflation of left atrial balloon, PI increased to 18 mmHg. IR was 1.6 mmHg.l-1.min. Again, hypoxic ventilation caused an isolated change in PI. Hypoxia increased PI from 18 to 28 mmHg (P less than 0.01). As in the condition of normal left atrial pressure, hypoxic ventilation did not affect IR. We conclude that, in an anesthetized intact canine preparation, hypoxic ventilation causes an isolated increase in the extrapolated pressure intercept of the pulmonary P-Q relationship. Furthermore the effects of hypoxic ventilation on pulmonary P-Q characteristics are not affected by the resting left atrial pressure. PMID- 1864780 TI - Shivering onset, metabolic response, and convective heat transfer during cold air exposure. AB - The onset and intensity of shivering of various muscles during cold air exposure are quantified and related to increases in metabolic rate and convective heat loss. Thirteen male subjects resting in a supine position and wearing only shorts were exposed to 10 degrees C air (42% relative humidity and less than 0.4 m/s airflow) for 2 h. Measurements included surface electromyogram recordings at six muscle sites representing the trunk and limb regions of one side of the body, temperatures and heat fluxes at the same contralateral sites, and metabolic rate. The subjects were grouped according to lean (LEAN, n = 6) and average body fat (NORM, n = 7) content. While the rectal temperatures fluctuated slightly but not significantly during exposure, the skin temperature decreased greatly, more at the limb sites than at the trunk sites. Muscles of the trunk region began to shiver sooner and at a higher intensity than those of the limbs. The intensity of shivering and its increase over time of exposure were consistent with the increase in the convective heat transfer coefficient calculated from skin temperatures and heat fluxes. Both the onset of shivering and the magnitude of the increase in metabolic rate due to shivering were higher for the LEAN group than for the NORM group. A regression analysis indicates that, for a given decrease in mean skin temperature, the increase in metabolic rate due to shivering is attenuated by the square root of percent body fat. Thus the LEAN group shivered at higher intensity, resulting in higher increases in metabolic heat production and convective heat loss during cold air exposure than did the NORM group. PMID- 1864781 TI - Activated neutrophils increase microvascular permeability in skeletal muscle: role of xanthine oxidase. AB - To determine the role of xanthine oxidase in the microvascular dysfunction produced by activated granulocytes, we examined the effect of xanthine oxidase depletion or inhibition on the increase in microvascular permeability produced by infusion of the neutrophil activator phorbol myristate acetate (PMA). Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient for total plasma proteins (sigma) in rat hindquarters subjected to PMA infusion in xanthine oxidase-replete and -depleted animals, in animals pretreated with the xanthine oxidase inhibitor oxypurinol, and in animals depleted of circulating neutrophils by pretreatment with antineutrophil serum (ANS). Xanthine oxidase depletion was accomplished by administration of a tungsten-supplemented (0.7 g/kg diet) molybdenum-deficient diet. In animals fed the tungsten diet, muscle total xanthine dehydrogenase plus xanthine oxidase activity was decreased to less than 10% of control values. Estimates of sigma averaged 0.84 +/- 0.04 in control hindquarters, whereas PMA infusion was associated with a marked increase in microvascular permeability (decrease in sigma to 0.68 +/- 0.03). PMA infusion also caused an increase in the amount of the radical-producing oxidase form of xanthine oxidase (from 3.9 +/- 0.05 to 5.6 +/- 0.4 mU/g wet wt). ANS pretreatment attenuated this permeability increase (sigma = 0.77 +/- 0.04) and diminished the rise in xanthine oxidase activity (4.9 +/- 0.5 mU/g wet wt). Xanthine oxidase depletion with the tungsten diet or pretreatment with oxypurinol had no effect on this neutrophil-mediated microvascular injury (sigma = 0.69 +/- 0.06 and 0.67 +/- 0.03, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864782 TI - Restricting environmental stimulation influences levels and variability of plasma cortisol. AB - Restricting stimulation from the environment has been shown to alter psychological and physiological states. The present study of 27 healthy subjects examines the effects of restricted environmental stimulation technique (REST) on plasma levels of cortisol and variability in plasma cortisol levels across repeated REST sessions. The REST environment consisted of a 1.2 X 1.2 X 2.4-m ovoid chamber containing 25 cm of saturated MgSO4 solution (sp gr 1.28) maintained at 34.5 degrees F. The buoyant supinely floating subject experienced a minimum of light, sound, and temperature awareness and spatial orientation. The non-REST environment was a cushioned reclining chair in a quiet dimly lit room. The 5-wk protocol consisted of four visits for blood sampling during a 2-wk baseline followed by eight REST or non-REST sessions, 40 min each, with blood samples taken on four nonsession days between sessions 5 and 8. Variability in plasma cortisol was expressed in terms of standard deviation. REST was associated with across-session decreases of 21.6% in plasma cortisol and 50.5% in plasma cortisol variability, whereas no changes in these measures occurred in non-REST. It is concluded that REST influences both static and dynamic aspects of adrenocortical function, possibly altering the feedback monitoring of plasma cortisol. PMID- 1864783 TI - Mechanical role of expiratory muscle recruitment during eupnea in supine anesthetized dogs. AB - To assess the mechanical role of the expiratory musculature during eupnea, we recorded the electromyographic (EMG) activity of the triangularis sterni, the external oblique, and the transversus abdominis in eight supine lightly anesthetized dogs and have measured the volume generated by the phasic activation of the expiratory muscles. Activation of the expiratory muscles was invariably associated with a decrease in lung volume below the relaxed position of the respiratory system, a volume equal to 41.3 +/- 8.4 ml. This volume represented roughly 20% of tidal volume generated during spontaneous breathing. The fractional expiratory contribution to the tidal volume was unrelated to the size of the animal. Traction on the forelimbs (limb extension), however, tended to enhance the phasic expiratory activation of both the triangularis sterni and the transversus abdominis in the majority of animals. Moreover, after limb extension, the fractional contribution of tidal volume attributed to the phasic activation of the expiratory muscles increased in all but one animal. During spontaneous breathing with the forelimbs extended, roughly 25% of tidal volume was found to be due directly to phasic expiratory muscle contraction. The present observations firmly establish that in supine lightly anesthetized dogs breathing at rest the expiratory component of tidal volume represents a substantial contribution. PMID- 1864784 TI - Early muscular and metabolic adaptations to prolonged exercise training in humans. AB - A short-term training program involving 2 h of daily exercise at 59% of peak O2 uptake (VO2max) repeated for 10-12 consecutive days was employed to determine the significance of adaptations in energy metabolic potential on alterations in energy metabolism and substrate utilization in working muscle. The initial VO2max determined before training on the eight male subjects was 53.0 +/- 2.0 (SE) ml.kg 1.min-1. Analysis of samples obtained by needle biopsy from the vastus lateralis muscle before exercise (0 min) and at 15, 60, and 99 min of exercise indicated that on the average training resulted (P less than 0.05) in a 6.5% higher concentration of creatine phosphate, a 9.9% lower concentration of creatine, and a 39% lower concentration of lactate. Training had no effect on ATP concentration. These adaptations were also accompanied by a reduction in the utilization in glycogen such that by the end of exercise glycogen concentration was 47.1% higher in the trained muscle. Analysis of the maximal activities of representative enzymes of different metabolic pathways and segments indicated no change in potential in the citric acid cycle (succinate dehydrogenase, citrate synthase), beta-oxidation (3-hydroxyacyl CoA dehydrogenase), glucose phosphorylation (hexokinase), or potential for glycogenolysis (phosphorylase) and glycolysis (pyruvate kinase, phosphofructokinase, alpha-glycerophosphate dehydrogenase, lactate dehydrogenase). With the exception of increases in the capillary-to-fiber area ratio in type IIa fibers, no change was found in any fiber type (types I, IIa, and IIb) for area, number of capillaries, capillary-to fiber area ratio, or oxidative potential with training.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864785 TI - Impedance electrodes positioned on proximal portions of limbs quantify fluid compartments in dogs. AB - Body resistance and reactance to the conduction of an alternating electrical current were measured using electrodes attached to distal and proximal portions of limbs in anesthetized dogs. Body impedance was calculated from these measurements obtained at 30-min time intervals during a control period and after intravenous administration of 0.9% saline. Extracellular (ECW) and total body water (TBW) were determined by bromide and heavy water dilution techniques, respectively. Baseline impedance obtained from proximal electrodes was related to ECW (r = 0.95, P less than 0.001) and TBW (r = 0.80, P less than 0.02). After saline infusion, proximal electrodes detected a significant fall in impedance (P less than 0.001), whereas distal electrodes did not (P = 0.06). Furthermore, ECW and TBW could be estimated from the drop of proximal impedance after this bolus infusion (r = 0.82, P less than 0.02, and r = 0.86, P less than 0.01, respectively), but not from distal impedance measurements. Proximally placed impedance electrodes are superior to traditionally used distal electrodes for assessment of body fluid changes in the dog. PMID- 1864786 TI - Phrenic neural output during hypoxia in dogs: constant-flow ventilation vs. spontaneous breathing. AB - We studied the effects of removing cyclic pulmonary afferent neural information on respiratory pattern generation in anesthetized dogs. Phrenic neural output during spontaneous breathing (SB) was compared with that occurring during constant-flow ventilation (CFV) at several levels of eucapnic hypoxemia. Hypoxia caused an increase in both the frequency and the amplitude of the moving time average (MTA) phrenic neurogram during both SB and CFV. The change in frequency as arterial saturation was reduced from 90 to 60% during SB was significantly higher than that during CFV [SB, 32.3 +/- 10.9 (SD) breaths/min; CFV, 10.3 +/- 5.8 breaths/min; P = 0.001]. By contrast, the increase in the amplitude of the MTA phrenic neurogram was smaller (SB, 0.62 +/- 0.68 units; CFV, 1.35 +/- 0.81 units; P = 0.01). The changes in frequency with hypoxia during both modes of ventilation resulted primarily from a shortening of expiratory time. Both inspiratory time and expiratory time were greater during CFV than during SB, but their change in response to hypoxia was not significantly different. We conclude that the amplitude response of the MTA phrenic neurogram to hypoxia is similar to that seen during hypercapnia; in the presence of phasic afferent feedback the MTA amplitude response is decreased and the frequency response is increased relative to the response observed in the absence of phasic afferents. PMID- 1864787 TI - Influence of cold, exercise, and caffeine on catecholamines and metabolism in men. AB - Recently we found that caffeine ingestion did not enhance either thermal or fat metabolic responses to resting in cold air, despite an increase in plasma epinephrine and free fatty acids. Theophylline, another methylxanthine, has been shown to be effective during exercise but not at rest during cold stress. Therefore we hypothesized that caffeine ingestion before exercise in cold air would have a thermal-metabolic impact by increasing fat metabolism and increasing oxygen consumption. Young adult men (n = 6) who did not normally have caffeine in their diet performed four double-blind trials. Thirty minutes after ingesting placebo (dextrose, 5 mg/kg) or caffeine (5 mg/kg) they either exercised (60 W) or rested for 2 h in 5 degrees C air. Cold increased (P less than 0.05) plasma norepinephrine while both caffeine and exercise increased (P less than 0.05) epinephrine. Serum free fatty acids and glycerol were increased, but there were no differences between rest and exercise or placebo and caffeine. Caffeine had no influence on either respiratory exchange ratio or oxygen consumption either at rest or during exercise. The exercise trials did not significantly warm the body, and they resulted in higher plasma norepinephrine concentrations and lower mean skin temperatures for the first 30 min. The data suggest that skin temperature stimulates plasma norepinephrine while caffeine has little effect. In contrast, caffeine and exercise stimulate plasma epinephrine while cold has minimal effect. Within the limits of this study caffeine gave no thermal or metabolic advantage during a cold stress. PMID- 1864788 TI - Effect of respiratory muscle fatigue on subsequent exercise performance. AB - The purpose of this study was to determine whether induction of inspiratory muscle fatigue might impair subsequent exercise performance. Ten healthy subjects cycled to volitional exhaustion at 90% of their maximal capacity. Oxygen consumption, breathing pattern, and a visual analogue scale for respiratory effort were measured. Exercise was performed on three separate occasions, once immediately after induction of fatigue, whereas the other two episodes served as controls. Fatigue was achieved by having the subjects breathe against an inspiratory threshold load while generating 80% of their predetermined maximal mouth pressure until they could no longer reach the target pressure. After induction of fatigue, exercise time was reduced compared with control, 238 +/- 69 vs. 311 +/- 96 (SD) s (P less than 0.001). During the last minute of exercise, oxygen consumption and heart rate were lower after induction of fatigue than during control, 2,234 +/- 472 vs. 2,533 +/- 548 ml/min (P less than 0.002) and 167 +/- 15 vs. 177 +/- 12 beats/min (P less than 0.002). At exercise isotime, minutes ventilation and the visual analogue scale for respiratory effort were larger after induction of fatigue than during control. In addition, at exercise isotime, relative tachypnea was observed after induction of fatigue. We conclude that induction of inspiratory muscle fatigue can impair subsequent performance of high-intensity exercise and alter the pattern of breathing during such exercise. PMID- 1864789 TI - Direct injury to the bronchial vasculature in anesthetized sheep. AB - Injury to the bronchial vasculature may contribute to liquid and solute leakage into the lung during noncardiac pulmonary edema. The purpose of this study was to measure changes in hemodynamics, pulmonary mechanics, extravascular lung water, and lung morphometry after selectively injuring the bronchial vasculature in anesthetized sheep. In two groups of seven sheep, we injected oleic acid (0.1 ml/kg) or normal saline directly into the bronchoesophageal artery. We measured systemic and pulmonary arterial pressures, cardiac output, oxygen saturation, pulmonary resistance and compliance, and lung volumes before and 1 and 4 h after injection. The lungs were removed for measurement of extravascular water, histology, and morphometry. Four hours after injection of oleic acid, cardiac output decreased but pulmonary arterial pressure did not change. In addition, pulmonary resistance increased and dynamic compliance and vital capacity decreased. Extravascular lung water was slightly but significantly greater in the oleic acid group. Histological examination showed interstitial edema and leukocytes in airway walls and sloughing of bronchial epithelium but little or no alveolar edema. Morphometric analysis showed significant thickening of airway walls. We conclude that direct injury to the bronchial vasculature increases lung resistance, decreases dynamic compliance, and increases extravascular lung water by the accumulation of an inflammatory infiltrate in airway walls. PMID- 1864790 TI - Upper airway cooling and l-menthol reduce ventilation in the guinea pig. AB - Cooling of the upper airway, which stimulates specific cold receptors and inhibits laryngeal mechanoreceptors, reduces respiratory activity in unanesthetized humans and anesthetized animals. This study shows that laryngeal cooling affects the pattern of breathing in the guinea pig and assesses the potential role of cold receptors in this response by using a specific stimulant of cold receptors (l-menthol). The response to airflows (30 ml/s, 10-s duration) through the isolated upper airway was studied in 23 anesthetized (urethan, 1 g/kg ip) guinea pigs breathing through a tracheostomy. Respiratory airflow, tidal volume, laryngeal temperature, and esophageal pressure were recorded before the challenges (control), during cold airflows (25 degrees C, 55% relative humidity), and during warm airflows (37 degrees C, saturated) with or without the addition of l-menthol. Whereas warm air trials had no effect, cold air trials, which lowered laryngeal but not nasal temperature, reduced ventilation (VE) to 85% of control, mainly by prolonging expiratory time (TE, 145% of control), an effect abolished by laryngeal anesthesia. Addition of l-menthol to the warm airflow caused a greater reduction in VE (41% of control) by prolonging TE (1,028% of control). Nasal anesthesia markedly reduced the apneogenic effect of l-menthol but did not affect the response to cold air trials. In conclusion, both cooling of the larynx and l-menthol in the laryngeal lumen reduce ventilation. Exposure of the nasal cavity to l-menthol markedly enhances this ventilatory inhibition; considering the stimulatory effect of l-menthol on cold receptors, these results suggest a predominant role of nasal cold receptors in this response. PMID- 1864791 TI - Plasma and muscle amino acid and ammonia responses during prolonged exercise in humans. AB - Plasma and muscle amino acid (AA) and ammonia (NH3) responses were measured during prolonged submaximal exercise in humans. Increased NH3 production during submaximal exercise has been attributed to the activity of the purine nucleotide cycle, without consideration of any possible contribution from AA. Six men cycled at 75% of maximal O2 uptake until exhaustion on two occasions after 2.5 days of ingestion of a high-carbohydrate or mixed diet. Plasma samples (antecubital vein) and muscle biopsies (vastus lateralis) were obtained at rest and during exercise and analyzed for plasma and muscle NH3 and AA as well as muscle metabolites. There were no significant diet effects in these parameters, so the majority of results focus on the effects of exercise. Plasma and muscle NH3 increased significantly from the onset and continued to increase throughout exercise. The total and total essential [AA] of muscle were significantly increased at exhaustion, whereas both the plasma and muscle branched-chain AA contents were unchanged. This suggests that protein catabolism was occurring during exercise and the branched-chain AA were used for energy and NH3 production. PMID- 1864792 TI - Albumin transport across pulmonary capillary-interstitial barrier in anesthetized dogs. AB - To evaluate albumin transport across the pulmonary capillary endothelial and interstitial barriers, we simultaneously measured blood-to-tissue (QA,t) and blood-to-lymph (QA,l) clearances of 125I-radiolabeled albumin as well as endogenous albumin clearance (Qa,l) in the canine lung in vivo (n = 10). Steady state prenodal lung lymph flows (Qw,l) and protein clearances were measured over a 2-h period at a constant capillary pressure (Pc, 13-33 cmH2O). Comparison between QA,t and QA,l as a function of Pc suggests that little of the albumin that crossed the capillary wall remained in the lung tissue, with most leaving in the lymph. Qw,l increased significantly as Pc increased, but lung tissue water was minimally affected. From the ratio of the clearance-Pc slopes for albumin and water, the albumin reflection coefficient was estimated to be 0.81 using QA,l and Qw,l and 0.56 using Qa,l and Qw,l. The permeability surface area product for the sum of blood-to-tissue and blood-to-lymph fluxes of labeled albumin (QA,t + QA,l) was 31 +/- 9 microliters/min, whereas that calculated from the blood-to-lymph flux of endogenous albumin (Qa,l) was 97 +/- 22 microliters/min. These data suggest that 1) both tissue and lymph accumulations of albumin must be considered when microvascular permeability is evaluated using protein tracers; 2) lymph clearance, but not tissue accumulation of albumin, was filtration dependent; and 3) lymph flow was an important contributor to the safety factor against edema formation over a moderate range of capillary pressures. PMID- 1864793 TI - Is fiber mitochondrial volume density a good indicator of muscle fatigability to isometric exercise? AB - The relationship between the ratio of interfibrillar mitochondrial volume density (Vvmit) to myofibrillar volume density (Vvmyo) and isometric fatigue characteristics of the human triceps surae was determined in six bodybuilders, six endurance athletes, and six active controls before and after 16 wk of isometric training at 30 or 100% maximal voluntary contraction (MVC) in six sedentary subjects in a unilateral exercise model. Time to fatigue at 30% MVC was significantly less in sedentary subjects before training than in the other subject groups, but it was similar to the other groups posttraining. Stereological analyses of type I fibers indicated that Vvmit/Vvmyo was less in bodybuilders than in other subjects. Training at 30% MVC increased type I fiber Vvmit/Vvmyo of the soleus by 11% but did not affect the gastrocnemii. Training at 100% MVC did not alter Vvmit/Vvmyo in any muscle, nor was this ratio changed in type II fibers by either training program. Despite the morphological differences, both training protocols increased relative endurance, although greater fatigue resistance was seen after training at 30% MVC. Correlation analyses indicated that isometric endurance and improvements in muscle endurance by isometric exercise were not dependent on increasing interfibrillar Vvmit or Vvmit/Vvmyo in either fiber type. PMID- 1864794 TI - Time course of hypoxic pulmonary vasoconstriction after endotoxin infusion in unanesthetized sheep. AB - Endotoxin [lipopolysaccharide (LPS)] has been reported to reduce hypoxic pulmonary vasoconstriction and thus increases venous admixture. The time course of this failure of pulmonary blood flow regulation was investigated in six chronically instrumented unanesthetized sheep after infusion of Escherichia coli LPS (1 microgram/kg). The change in left pulmonary arterial blood flow (LPBF, ultrasonic transit time) in response to unilateral lung hypoxia (10 min of N2 alternately to the left and right lungs) was compared before and at various time intervals after the administration of LPS. During baseline conditions, LPBF was 33% of total cardiac output and decreased to 15% when the left lung was ventilated with a hypoxic gas mixture. One hour after endotoxin infusion, LPBF remained at 33% of total cardiac output yet only decreased to 28% during the hypoxic challenge. The response to one-lung hypoxia was still significantly depressed 10 h post-LPS administration. It is concluded that hypoxic pulmonary vasoconstriction is almost completely abolished for a prolonged time period after a small dose of LPS. PMID- 1864795 TI - Localization of the sites of pulmonary vasomotion by use of arterial and venous occlusion. AB - In this study, we present a new approach for using the pressure vs. time data obtained after various vascular occlusion maneuvers in pump-perfused lungs to gain insight into the longitudinal distribution of vascular resistance with respect to vascular compliance. Occlusion data were obtained from isolated dog lung lobes under normal control conditions, during hypoxia, and during histamine or serotonin infusion. The data used in the analysis include the slope of the arterial pressure curve and the zero time intercept of the extrapolated venous pressure curve after venous occlusion, the equilibrium pressure after simultaneous occlusion of both the arterial inflow and venous outflow, and the area bounded by equilibrium pressure and the arterial pressure curve after arterial occlusion. We analyzed these data by use of a compartmental model in which the vascular bed is represented by three parallel compliances separated by two series resistances, and each of the three compliances and the two resistances can be identified. To interpret the model parameters, we view the large arteries and veins as mainly compliance vessels and the small arteries and veins as mainly resistance vessels. The capillary bed is viewed as having a high compliance, and any capillary resistance is included in the two series resistances. With this view in mind, the results are consistent with the major response to serotonin infusion being constriction of large and small arteries (a decrease in arterial compliance and an increase in arterial resistance), the major response to histamine infusion being constriction of small and large veins (an increase in venous resistance and a decrease in venous compliance), and the major response to hypoxia being constriction of the small arteries (an increase in arterial resistance). The results suggest that this approach may have utility for evaluation of the sites of action of pulmonary vasomotor stimuli. PMID- 1864796 TI - Respiratory epithelium-dependent inhibition of protein kinase C of airway smooth muscle cells. AB - We have examined the effect of phorbol myristate acetate (PMA) on airway smooth muscle (ASM) in the presence and absence of respiratory epithelium (RE) and analyzed the dependence of this response on extracellular sodium, Na+/H+ exchange, calcium, and cyclooxygenase products; we determined both the resting membrane potential and isometric force developed by ASM preparations. Removal of RE had no effect on the values of the resting membrane potential of ASM cells. In the presence of RE in the preparation, both electrical and contractile responses to PMA (10(-5) M) were significantly different compared with the response of ASM to PMA without RE. When the RE was present, stimulation of protein kinase C caused only a biphasic response in both membrane potential and isometric force. In either the presence or absence of RE, amiloride (10(-5) M) and a low-sodium solution inhibited both electrical and contractile changes of ASM cells caused by PMA. In the presence or absence of RE, verapamil (10(-5) M) attenuated (P less than 0.05) both electrical and contractile responses of ASM cells as induced by PMA. Verapamil, however, had no effect on the last phase of PMA-induced response. Pretreatment of preparations with indomethacin (10(-6) M) changed the PMA-induced response of ASM with RE to a response usually observed in ASM without RE. Finally, the incubation of tracheal preparations without RE with prostaglandin E2 (10(-8) M) altered the response of these preparations in such a way that their electrical and contractile response to PMA was essentially identical to the PMA response observed in preparations with an intact RE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864797 TI - Alveolar air-tissue interface and nuclear magnetic resonance behavior of lung. AB - Inflated lungs are characterized by a short nuclear magnetic resonance (NMR) free induction decay (rapid disappearance of NMR signal), likely due to internal (tissue-induced) magnetic field inhomogeneity produced by the alveolar air-tissue interface. This phenomenon can also be detected using temporally symmetric and asymmetric NMR spin-echo sequences; these sequences generate a pair of NMR images from which a difference signal (delta) is obtained (reflecting the signal from lung water experiencing the air-tissue interface effect). We measured delta in normal excised rat lungs at inflation pressures of 0-30 cmH2O for asymmetry times (a) of 1-6 ms. Delta was low in degassed lungs and increased markedly with alveolar opening when measured at a = 6 ms (delta 6 ms); delta 6 ms varied little during the rest of the inflation-deflation cycle. Delta 1 ms (a = 1 ms) did not vary significantly on inflation and deflation. Measurements of delta at a = 3 and 5 ms generally lay between those of delta 1 ms and delta 6 ms. These findings, which are consistent with theoretical predictions, suggest that measurements of delta at appropriate asymmetry times are particularly sensitive to alveolar opening and may provide a means of distinguishing alveolar recruitment from alveolar distension in the pressure-volume behavior of the lung. PMID- 1864798 TI - Factors that determine the hemodynamic response to inhalation anesthetics. AB - The hemodynamic response to inhalation anesthesia is influenced by three factors: 1) the specific drug, 2) the dose, and 3) individual characteristics of the subject. To investigate the importance of these factors on the cardiovascular response, we administered five doses [0, 0.5, 1.0, 1.5, and 2.0 minimum alveolar concentration (MAC)] of enflurane, halothane, and isoflurane to each of six dogs. Twelve hemodynamic variables were measured. For all variables, a change in the dose of each drug produced a consistent effect in each dog. Increases in dose resulted in significant decreases in seven variables [left ventricular ejection fraction, cardiac index (CI), stroke volume index (SVI), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), left ventricular stroke work index (LVSWI), and heart rate (HR)] and a significant increase in one variable [central venous pressure (CVP)]. In contrast, the response of individual dogs to different drugs was not consistent. For seven variables [MAP, MPAP, LVSWI, CVP, pulmonary capillary wedge pressure (PCWP), end-diastolic volume index (EDVI), and end-systolic volume index (ESVI)], a significant difference in the responses of a dog to two drugs was greater than zero, whereas a significant difference in the response of at least one other dog to the same two drugs was less than zero (discordant dog-drug interactions). Thus, in contrast to the consistency of the cardiovascular response to changes in dose, the hemodynamic response to different drugs was inconsistent among dogs. We also studied the effect of fluid challenge on hemodynamic response at 1.5 or 2.0 MAC of the three drugs given to each dog.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864799 TI - Adipose tissue volume measured by magnetic resonance imaging and computerized tomography in rats. AB - The primary purpose of this study was to investigate the viability of magnetic resonance imaging (MRI) as a means of measuring the body composition of rodents. To do so we compared adipose tissue (AT) volumes measured by MRI with those obtained by X-ray computerized tomography (CT) in a group of rats (n = 17) varying in weight (465-815 g) and percent body fat (5.4-31.1%), with the latter determined by chemical analysis. For both MRI and CT, AT volumes (cm3) per transverse slice (3-mm thickness, 21-mm centers) were determined using a computer based image analysis system that permitted detailed comparisons of both visceral and subcutaneous AT depots. Total AT volumes were calculated using a linear interpolation of AT areas obtained on consecutive slices. Correlation coefficients between MRI and CT for visceral [r = 0.98, standard error of estimate (SEE) = 6.8 cm3], subcutaneous (r = 0.98, SEE = 6.5 cm3), and total AT volumes (r = 0.99, SEE = 9.0 cm3) were highly significant (P less than 0.001). Both MRI- and CT-predicted AT mass (assuming fat density = 0.90 g/ml) correlated strongly with chemically extracted lipid (grams) values (r = 0.98, SEE 9.6 g and r = 0.99, SEE = 6.9 g, respectively). Post hoc Scheffe contrasts demonstrated that the mean AT and lipid mass values derived by the three methods were not significantly different (P = 0.01). No systematic differences were observed because the regression lines derived for either MRI or CT vs. chemical analysis were not significantly different from the identity line.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864800 TI - Effect of preexisting brain ischemia on sympathetic nerve response to intracranial hypertension. AB - The performance of the sympathetic nervous system during sustained moderate cerebral ischemia (CI) was examined in the present study. For this purpose, a Cushing response was elicited repeatedly during incomplete global CI in anesthetized artificially ventilated cats after vagotomy and baroreceptor denervation. In control animals without CI, sympathetic activity in response to brief elevation of intracranial pressure (ICP) showed a well-repeatable two-phase reaction. During CI there was a progressive deterioration of background sympathetic nerve discharge (SND) over a period of 30 min. SND response to repeated elevation of ICP was initially similar to control response but later with progression of CI was seriously changed. 1) Instead of the usual hyperactivation, sympathetic nerve activity was depressed during intracranial hypertension. 2) The characteristic desynchronized activity either appeared later during the reperfusion period or remained absent. The progressive loss of SND response to raised ICP in developed CI was compared with the changes seen in experiments in which repeated ICP elevations were superimposed on asphyxia. These findings suggest that the sympathetic component of the Cushing reaction strongly depends on the actual state of brain stem autonomic circuits and may be seriously altered in pathological situations involving ischemic brain injury. PMID- 1864801 TI - Inhomogeneity of ventilatory unit volume and its effects on reactive gas uptake. AB - This study addressed the question of whether variations in the volume of alveoli and alveolar ducts forming single units of ventilation can significantly influence the distribution and uptake of inspired reactive gases. Quantitative serial section analyses of vascular perfusion-fixed rat lungs were used to determine the anatomic dead space proximal to specific ventilatory units as well as the gas volume of these ventilatory units. Three reconstructions, each consisting of ventilatory units distal to a specific bronchus, were carried out. The number of ventilatory units for each reconstruction varied from 26 to 71. The average ventilatory unit volume for the three reconstructions [0.53 +/- .03 (SE) mm3] was not significantly different from measurements based on random sampling. The distribution of ventilatory unit volume was diverse, with 15% of the population having a volume less than 0.3 mm3 and 9% of the population having a volume greater than 1.0 mm3. For a gas of relatively low reactivity (e.g., oxygen) the predicted oxygen uptake per unit surface area did not vary significantly between ventilatory units. The predicted oxygen uptake was approximately 92% of the uptake in the absence of gradients in oxygen concentration between ventilatory units. For a highly reactive gas (e.g., ozone), the predicted uptake per unit surface area in the proximal portions of larger ventilatory units was significantly greater than the average uptake. These results suggest that focal areas of injury likely result from exposure to inhaled reactive gases. PMID- 1864802 TI - PET evaluation of pulmonary vascular permeability: a structure-function correlation. AB - We compared regional measurements of the pulmonary transcapillary escape rate (rPTCER) for 68Ga-transferrin, obtained by positron emission tomography (PET), with morphometric data obtained from corresponding tissue samples in six anesthetized mechanically ventilated dogs, 1 h after oleic acid administration to either the left caudal lobe (0.015 ml/kg; Lobar group, n = 3) or the right atrium (0.08 ml/kg; Diffuse group, n = 3). Data were obtained from 48 regions in both injured and control lobes (right caudal lobes from the Lobar group). The volume density of edematous or hemorrhagic alveoli at the light-microscopic level was directly related to rPTCER (r = 0.82 for regions with rPTCER values less than 700 x 10(-4) min-1). Likewise, the relative surface of abnormal capillary endothelium and alveolar epithelium at the electron-microscopic level correlated well with rPTCER (r = 0.87 for regions with rPTCER less than 1,200 X 10(-4) min-1). We conclude that the rPTCER measurements obtained with PET reflect the morphological heterogeneity present in oleic acid-damaged lung tissue. Thus rPTCER measurements should be useful as a noninvasive quantitative index of lung injury. Furthermore, the tomographic image display of rPTCER may allow PET to be used as a "physiological probe" to guide tissue excision for later histological evaluation when lung injury is heterogeneous. PMID- 1864803 TI - Respiratory-related activity of cricothyroid muscle in awake normal humans. AB - The role of the cricothyroid muscle (CT) in respiration is unclear. To examine the respiratory-related electrical activity of the CT, we measured its electromyogram (EMG) and compared it with that of the alae nasi (AN) in eight healthy subjects. During quiet breathing the CT EMG phasing was inspiratory in seven subjects. This pattern was similar to the AN with respect to phasing and shape of the integrated EMG. The onset of phasic CT and AN activity related to inspiration preceded flow by 173 +/- 39 and 570 +/- 76 (SE) ms, respectively (P less than 0.01). We measured the duration from onset of phasic activity to peak of the EMG (TA) and the total cycle duration (TT). TA/TT of the CT was 0.29 +/- 0.02, similar to that of the AN (0.28 +/- 0.03). Inspiratory resistive loading, panting, and voluntary hyperventilation increased CT activity above the peak level seen during tidal breathing. Voluntary glottic closure increased CT activity to a level above tonic but below peak tidal activity. The findings suggest that the phasic electrical activity of the CT simulates predominantly that of an upper airway dilator. PMID- 1864804 TI - Cricothyroid muscle responses to increased chemical drive in awake normal humans. AB - To examine the response of the cricothyroid muscle (CT) to increased chemical drive, we measured its electromyogram simultaneously with that of the alae nasi (AN) in seven normal awake subjects. During both progressive hyperoxic hypercapnia and hypoxia, peak integrated inspiratory activity (moving time average, MTA) of the CT and AN increased as a power function of mean inspiratory flow (ratio of tidal volume to inspiratory time, VT/TI), given by MTA = a(VT/TI)b + c (where a, b, and c are constants). The exponent b varied from 0.009 to 3.4 among subjects but was correlated between CT and AN both during hypercapnia (r = 0.86) and hypoxia (r = 0.81). The onset of inspiratory activity of the CT and AN preceded that of inspiratory flow. Expressed as a percentage of expiratory time, the CT lead time rose from 7% at rest to 20% during hyperpnea. The corresponding values for the AN were from 22 to 52% (both P less than 0.03). Thus the pattern of response of the CT and AN is similar and related to that of the inspiratory muscles in a curvilinear manner. The findings suggest that during chemical stimulation the electrical activity of the CT is analogous to that of the AN, an upper airway dilator. PMID- 1864805 TI - Pressure-diameter relationships of the upper airway in awake supine subjects. AB - In awake supine normal subjects, dimensional changes of the oropharyngeal airway were measured during exposure to negative intraluminal pressures. The pressure was generated 1) "actively" by subjects inspiring against an externally occluded airway or 2) "passively" by external suction at the mouth during voluntary glottic closure with no inspiratory effort. Airway dimensions were imaged with X ray fluoroscopy and anteroposterior diameters measured at levels corresponding to cervical vertebra 3 and 4 (C3 and C4). Cephalad axial displacement of the hyoid bone (CDHY) was also measured. During the "active" maneuver, airway diameters and position were maintained at resting levels despite airway pressure up to -15 cmH2O. In contrast, during the passive maneuver at -15 cmH2O, C3 was only 15 +/- 9% and C4 only 47 +/- 8% of control; CDHY was 5.6 +/- 1.8 mm. In three subjects airway wall apposition occurred and persisted until an active inspiratory effort. We conclude that, in the absence of inspiratory effort, negative oropharyngeal airway pressures result in marked narrowing and cephalad displacement of the upper airway, even during wakefulness. Therefore, our data suggest that the complex interaction of upper airway and thoracic muscle activity is critical in determining the effective compliance and patency of the upper airway, which is readily collapsible even in normal subjects. PMID- 1864806 TI - Influence of posterior cricoarytenoid muscle activity on pressure-flow relationship of the larynx. AB - We examined the effect of posterior cricoarytenoid (PCA) muscle activity on the pressure-flow (PV) relationship of the larynx in five anesthetized tracheostomized dogs. The PCA activity was recorded using bipolar fine-wire electrodes, expressed as a percentage of the quiet breathing level and altered by mechanical ventilation, changes in lung volume, and chest wall compression. Subglottic pressure was recorded while a constant flow of air was passed through the upper airway. In the absence of PCA activity the PV relationship was alinear and could be described by a power function (P = K0Va, where K0 and a are constants). The slope of the log P-log V plots in the absence of PCA and thyroarytenoid activity was 1.83 +/- 0.02 (SD), whereas with increasing PCA activity it was 1.88 +/- 0.11. An effective hydraulic diameter (DH) was calculated for 20% increments of PCA activity, and in two dogs glottic diameter (Dg) was calculated from glottic area measurements obtained by fiber-optic laryngoscopy. Both DH and Dg increased linearly with increasing PCA activity. Denervation of the cricothyroid muscle had no systematic effect on laryngeal resistance. The results indicate that the PV relationship of the larynx may be described by a power function with a single exponent, the magnitude of which is independent of glottic dilator muscle activity and consistent with orifice flow. However, laryngeal diameter increases linearly with PCA activity in the range studied. PMID- 1864807 TI - Adaptive modeling of the human rib cage in median sternotomy. AB - This paper describes a limited computer-analyzed kinematic model of the rib cage that can be adapted to individual subjects. Also described is its validation and use in assessing the changes in chest wall shape after coronary artery bypass graft (CABG) surgery in 12 patients. The positions of a small number of anatomic locations on the thoracic spine, ribs, manubrium, and sternum are measured from lateral and posterior-anterior chest radiographs. The computer program puts these two views together removing the magnification and reconstructs any missing points to give a three-dimensional picture of the rib cage to which mathematical models of the bones are scaled. The patients had chest radiographs taken at total lung capacity (TLC) and residual volume (RV) to investigate the source of the restrictive ventilatory defect that follows CABG. The predictions from the model were tested by comparing full-sized computer plots with the actual chest radiographs. The estimates of the bony structures were accurate to +/- 3 degrees for orientations and +/- 6 mm for positions. We found reduced rib motion both "pump-handle" (theta) and "bucket handle" (psi) going from theta, psi left, psi right = 9 degrees, 10 degrees, 14 degrees to 4 degrees, 10 degrees, 9 degrees, respectively, after surgery with P less than 0.025, 0.42, 0.07. The angles were measured from the horizontal and increased caudally. There was also reduction in the range of angles subtended by the arc of the thoracic vertebrae between TLC and RV, which went from 12 degrees to -1 degrees (P less than 0.015). These data explain the fall in lung volumes that follow CABG and provide insight into the contribution made by the ribs and spine in full inspiration and full expiration. PMID- 1864808 TI - Exercise training elevates RMR during moderate but not severe dietary restriction in obese male rats. AB - This study examined the effects of 11 wk of exercise training (E) on resting O2 uptake (RMR) and the composition of diet-induced weight loss in obese male Sprague-Dawley rats (n = 48). The rats underwent one of three levels of dietary treatment: ad libitum (AL), moderate restriction (MR), and severe restriction (SR). Compared with AL-CC (cage confined; 647 +/- 13 g), the AL-E (84% of AL-CC), MR-CC (77%), MR-E (77%), SR-CC (63%), and SR-E (63%) groups were all reduced in body mass. At the MR level, E significantly reduced fat mass (FM; MR-CC 73 +/- 5, MR-E 45 +/- 5 g) and increased water mass (WM; MR-CC 307 +/- 5, MR-E 329 +/- 5 g) compared with CC. In contrast, no significant differences existed between the SR CC and SR-E groups. Exercise training did not result in conservation of protein mass at any level of dietary intake. Exercise training significantly elevated RMR (on a kg0.75 basis) by approximately 7% for the AL-E and MR-E groups compared with their respective dietary counterparts. These findings may help reconcile the conflicting results present in the literature with respect to the effects of exercise training during diet-induced weight loss. That is, studies using relatively severe dietary restrictions are less likely to demonstrate exercise induced changes in RMR, FM, and WM than those employing moderate dietary restrictions. PMID- 1864809 TI - Use of a triaxial magnetometer for respiratory measurements. AB - We describe a triaxial magnetometer (Tri-mag) system, which consists of a transmitter, four sensors, a processing unit, and a personal computer (PC). The Tri-mag processing unit outputs the position of each sensor relative to the transmitter in three orthogonal coordinates, and this information is communicated to the PC. First, we demonstrated that within a defined octant of a sphere in which the center is the transmitter, we can measure radial distances with an accuracy of +/- 1 mm over a range extending from 10 to 70 cm from the transmitter. Second, we recorded the three-dimensional movement of sensors on the anterior and posterior surfaces of the chest wall during maximum voluntary ventilation in four normal men; all sensors were placed in the midsagittal plane of the body. Anterior sensors were located on the sternum at the level of the third intercostal space and at 2 cm above the umbilicus, whereas posterior sensors were located on the posterior spine at the same vertical levels as the anterior sensors. In all subjects the following was found. 1) Both anterior sensors moved anterior and cephalad during inspiration. The anterior thoracic sensor showed greater vertical than anteroposterior (A-P) movement, whereas the anterior abdominal sensor showed greater A-P than vertical movement. 2) Inspiration was associated with spinal extension, whereas expiration was associated with spinal flexion. Third, we used Tri-mag information to 1) measure tidal volume (VT) over a range extending from 500 ml to inspiratory capacity and 2) measure the change in end-expiratory lung volume (EELV) over a range extending from FRC to FRC plus a minimum of 1.5 liters. Our results indicate that greater than 96% of the changes in VT and greater than 82% of the changes in EELV can be accounted for by changes in A-P, vertical, and lateral dimensions of the chest wall. PMID- 1864810 TI - Effect of denervation or unweighting on GLUT-4 protein in rat soleus muscle. AB - The purpose of this study was to test the hypothesis that the decreased capacity for glucose transport in the denervated rat soleus and the increased capacity for glucose transport in the unweighted rat soleus are related to changes in the expression of the regulatable glucose transporter protein in skeletal muscle (GLUT-4). One day after sciatic nerve sectioning, when decreases in the stimulation of soleus 2-deoxyglucose (2-DG) uptake by insulin (-51%, P less than 0.001), contractions (-29%, P less than 0.05), or insulin and contractions in combination (-40%, P less than 0.001) were observed, there was a slight (-18%, NS) decrease in GLUT-4 protein. By day 3 of denervation, stimulation of 2-DG uptake by insulin (-74%, P less than 0.001), contractions (-31%, P less than 0.001), or the two stimuli in combination (-59%, P less than 0.001), as well as GLUT-4 protein (-52%, P less than 0.001), was further reduced. Soleus muscle from hindlimb-suspended rats, which develops an enhanced capacity for insulin stimulated glucose transport, showed muscle atrophy similar to denervated soleus but, in contrast, displayed substantial increases in GLUT-4 protein after 3 (+35%, P less than 0.05) and 7 days (+107%, P less than 0.001). These results indicate that altered GLUT-4 expression may be a major contributor to the changes in insulin-stimulated glucose transport that are observed with denervation and unweighting. We conclude that muscle activity is an important factor in the regulation of GLUT-4 expression in skeletal muscle. PMID- 1864811 TI - Competitive control of myosin expression: hypertrophy vs. hyperthyroidism. AB - The competition between two opposing influences on the phenotypic expression of skeletal muscle myosin were studied to determine which was the dominant regulator. Experimental hyperthyroidism, which induces fast myosin expression, was produced by subcutaneous implantation of a 40-day constant-time-release triiodothyronine pellet. Compensatory hypertrophy, which induces slow myosin expression, was produced by surgical removal of a synergistic hindlimb muscle. Hyperthyroidism increased the percentage of type II fibers and the fast myosin isoforms in both the plantaris and soleus muscles. Hypertrophy significantly increased the percentage of type I fibers and the slow myosin type in the plantaris and soleus muscles. However, with the simultaneous introduction of hyperthyroidism and hypertrophy, only the hyperthyroid effects were observed. Hyperthyroidism and not physiological demand was found to be the dominant regulator of skeletal muscle myosin expression. PMID- 1864812 TI - Eyewitness memory for a touching experience: accuracy differences between child and adult witnesses. AB - Children, ages 5-6 and 9-10 years, and adults spent 6 min with a man (toucher) who administered a test that required interpersonal touch. The test was briefly interrupted by a woman (intruder). Afterward, the participant-witnesses provided a memory report that included free recall, answers to objective-memory questions, and two lineup identifications. Relative to the adults and older children, the 5- to 6-year-olds gave less complete free recall and made more errors in answering objective questions about the features and actions of the toucher and the intruder. On recognition tests, both the 5- to 6- and 9- to 10-year-olds were somewhat less likely than adults to make accurate lineup decisions about the toucher and much less likely to accurately identify the briefly seen intruder. Children may remember even salient stimuli and actions more poorly than adults do, but there was no evidence that children misremembered touches that did not occur. PMID- 1864813 TI - Negative affectivity as the underlying cause of correlations between stressors and strains. AB - The extent to which negative affectivity (NA), the tendency to experience a wide range of negative emotions, inflated correlations between chronic job stressors and strains was examined in this study. NA was found to account for a large proportion of shared variance between stressors and physical strains (as indicated by absence, doctor visits, and physical symptoms). Contrary to the results of Brief, Burke, George, Robinson, and Webster (1988), NA did not account for much of the variance shared by stressors and affective strains (job satisfaction, anger, and feelings of stress and frustration). Reasons for the failure of this and several earlier studies to successfully replicate Brief et al.'s results are explored. PMID- 1864815 TI - Hemoglobinopathies. PMID- 1864814 TI - Influence of job characteristics on the acceptability of employee drug testing. AB - Measures of the acceptability of employee drug testing were obtained from a sample of college students (N = 371) and a second sample of nontraditional, older college students (N = 112) and were correlated with job-analysis data from the Position Analysis Questionnaire (PAQ) and Dictionary of Occupational Titles (DOT) databases, and with measures of perceived danger from impaired performance in each job. Both PAQ and DOT data accounted for variance in ratings of acceptability. Perceptions of danger were the best single predictor of acceptability and appeared to mediate the relationships between job characteristics and the acceptability of employee drug testing. PMID- 1864816 TI - Sickle cell vaso-occlusion. AB - A polymerizable cell is a requirement for sickle cell vaso-occlusion, but other factors clearly modulate the course of the disease. Hemolysis produces a young red cell population that is capable of adhesion and may result in polymer formation in cells that would otherwise have remained deformable during transit through the microcirculation owing to prolonged delay time for polymerization. In addition, a young red cell population will have a higher activity of K:Cl cotransport, which is capable of rapidly dehydrating cells under acid conditions, thus promoting a vicious circle of hemolysis and adhesion. Transient occlusion may stimulate the release of vasoactive substances, which may lead to involvement of a larger area. In the past, research aimed at reducing the incidence of painful crisis was primarily focused on antisickling agents. Currently, hydroxyurea, which increases the level of fetal hemoglobin, which may be described as a natural antisickling agent, is undergoing clinical trials. Future research may involve agents that inhibit sickle cell adhesion, K:Cl cotransport, or vasoactive substances. PMID- 1864817 TI - Somatic gene therapy. AB - Many problems obviously continue to exist in gene transfer using retroviruses as a means of inserting foreign DNA into hematopoietic stem cells, especially with regulated genes such as the human beta globin genes. First, it is unclear whether the available retroviral vectors will infect enough stem cells for gene transfer to be successful over the long term. Second, there may be sequences necessary for normal beta globin gene expression that may also inhibit the normal retroviral life cycle, thus decreasing the efficiency of gene transfer or gene expression. It seems clear that in order to optimize the success of gene transfer, the highest possible titer of viral production is necessary. New approaches are aimed at increasing viral titer. The transfect/infect method appears useful. Growth factors may also be useful by increasing stem cell proliferation. Single growth factors may not be sufficient to optimize stem cell cycling. To date, interleukin 3 seems to be the single most useful growth factor, although interleukin-3 with interleukin-6 or other combinations of growth factors including interleukin-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) appear to have potential. Future work also is required to optimize the number of marrow stem cells needed for successful transplantation. Long-term bone marrow culture and stromal cell cultures may provide new and improved marrow culture conditions for achieving this goal. Improvements in the efficiency of both gene transfer and gene expression are necessary before we can consider the concept of gene transfer for the treatment of various hematologic genetic diseases in humans. PMID- 1864818 TI - The distinct pathobiology of sickle cell-hemoglobin C disease. Therapeutic implications. AB - The data available clearly establish that the hyperconcentration of hemoglobin C and S inside SC cells is the main and driving mechanism for the pathologic behavior of these cells. It facilitates the polymerization of Hb S, but it also favors the tendency of Hb C to induce the formation of crystals and aggregates, abnormal morphologic shapes, and abnormally dense reticulocytes, through a particularly active K:Cl cotransport. Why these cells are endowed with a particularly active K:Cl cotransport is still a mystery; it is disproportionate with the extent of the hemolysis and the number of young cells. Is there an abnormal interaction between Hb C and the K:Cl cotransport protein in the inner aspect of the membrane? Are there abnormal interactions between Hb C and the other transport mechanisms that balance the shrinking capacity of K:Cl cotransport (as Na/H exchange)? Only future work will tell. In any case, SC disease is unique among the hemoglobinopathies in that a single intervention could correct all abnormalities: the restitution of the normal MCHC, as proven experimentally by Fabry et al. Hence, effort should be centered on looking for compounds that increase red cell volume, because in SC cells, increases in volume will not distort the cell, but restore it to the normal red cell volume and the normal red cell shape. This luxury is not available for cells with normal MCHC (the majority of the red cells in SS blood), because increasing their volume will progressively turn them into spheres, a rheologically disadvantaged shape. PMID- 1864819 TI - The interactions of alpha-thalassemia with hemoglobinopathies. AB - Because of their high prevalence throughout the world, alpha-thalassemia and hemoglobinopathies often occur in the same individual. Southern blot hybridization analysis of the alpha-globin gene cluster permits the detection of the common deletion alpha-thalassemias and the definition of the phenotypes affiliated with the interactions of alpha-thalassemia and hemoglobinopathies. Important insights into the pathophysiology of Hb SS have been gained, and the nature of the perturbation of heterozygous hemoglobinopathies by alpha thalassemia has been established. PMID- 1864820 TI - Noninvasive diagnostic imaging in hemoglobinopathies. AB - We have provided a global review of the current applications of newer modalities, particularly MR imaging, as applicable to the major manifestations of sickle cell disease, the most common hemoglobinopathy. There is a need for well-designed prospective longitudinal studies utilizing MR imaging to gain further insight into the pathophysiology of this intriguing disease. Additionally, MR imaging, because of lack of ionizing radiation, is ideally suited for long-term sequential studies and may thus provide an objective means for monitoring response to therapy. PMID- 1864821 TI - Ophthalmologic complications in hemoglobinopathies. AB - The various forms of sickle cell disease share the common feature of an abnormal globin chain that, under certain conditions such as hypoxia, results in the sickling of red blood cells and obstruction of blood vessels. The ophthalmic manifestations of sickle cell disease are present in various segments of the eye, which include the conjunctiva, iris, retina, and optic nerve. Patients with SC disease and SB thalassemia tend to have more severe ophthalmic complications than their counterparts with the more severe systemic form of sickle cell disease--SS disease. It is important for patients with sickle cell disease to have periodic examinations by ophthalmologists, because the early identification of peripheral retinal disease can be adequately treated, with preservation of vision. Without treatment, peripheral retinal changes can lead to retinal detachments and vitreous hemorrhages, which account for the majority of visual impairment in patients with sickle cell disease. PMID- 1864822 TI - Bone marrow transplantation in thalassemia. AB - Since 1983, 350 patients aged 1 to 19 years with beta-homozygous thalassemia were given infusions of HLA-identical marrow after high doses of busulphan and cyclophosphamide. Survival and event-free survival leveled off about 1 year after bone marrow transplantation at 82% and 75%, respectively. In 172 consecutive patients who were treated with our current regimen since June 1985, a multivariate analysis demonstrated that portal fibrosis, hepatomegaly, and a history of inadequate chelation therapy were significantly associated with reduced probabilities of survival and event-free survival. The patients were divided into three classes on the basis of the presence of hepatomegaly, portal fibrosis, and inadequate chelation therapy. Class 1 had none of the factors and class 3 had all three factors; class 2 had different associations of two out of the three factors. For class 1 patients, the 3-year probabilities of survival and event-free survival were 97% and 94%, respectively. For class 2 patients, the probabilities were 86% and 83%, and for class 3 patients, 58% and 52%. Bone marrow transplantation from HLA-identical donors is followed by a high probability of event-free survival in thalassemic patients, particularly if they belong to class 1. PMID- 1864823 TI - Management of thalassemia major (Cooley's anemia). AB - Cooley's anemia patients, treated with a combined regimen of blood transfusions and chelation therapy, can look forward today to near-normal survival and excellent quality of life. Transfusion therapy should be directed at maintaining a hemoglobin baseline (greater than or equal to 10 g/dL) adequate to prevent hypoxia and its consequences: bone marrow expansion and cardiomegaly. Chelation therapy should aim at a very reduced Fe overload, to be monitored by the serum ferritin level. Several oral Fe chelating drugs currently being developed appear promising; none, however, is ready for general use as yet. Transplantation of bone marrow from a compatible sibling can cure Cooley's anemia; however, this therapy is currently only applicable to a small percentage of patients. PMID- 1864824 TI - Management of pregnancy in sickle cell syndromes. AB - We have seen a marked decrease in maternal and perinatal morbidity and mortality among pregnant patients with sickle cell disease. This has been the result of coordinated efforts with the obstetric and hematologic teams. Patients are counseled prior to pregnancy regarding the risks and are given the opportunity to modify their life style to prepare for the additional metabolic burden of gestation. Once pregnant, they are instructed in the techniques to recognize and avoid complications. They are observed frequently for the appearance of pain crisis and other medical and obstetric complications. If complications are identified, they should be treated aggressively. Transfusion therapy is important in the management of patients; however, prophylactic transfusion does not change outcome. Although significant laboratory techniques aid in fetal and maternal supervision, the universal fundamentals of good clinical perinatal care provided through the combined efforts of the obstetrician and hematologist contribute to the framework for the modern management and successful outcome of patients with sickle cell disease during pregnancy. PMID- 1864825 TI - Neologisms and idiosyncratic language in autistic speakers. AB - Language samples from matched groups of 80 autistic, mentally handicapped, and normally developing children were coded for the presence of neologisms and/or idiosyncratic language use. Cognitive, social, or linguistic factors that might account for these errors were identified and assessed. More autistic subjects used neologisms and idiosyncratic language than age- and language skill-matched control groups. No single factor or combination of factors was responsible for this difference. Across diagnostic groups, similar patterns of error were noted, except that the autistic subjects were more likely to use words inappropriately that had no phonological or semantic similarity to the intended English word. For the autistic groups, the frequency of idiosyncratic language increased with language complexity. In contrast, such errors decreased with language skill in the mentally handicapped group. Theoretical implications for determining the nature and source of the language disorder associated with autism are discussed. PMID- 1864826 TI - The effects of two levels of linguistic constraint on echolalia and generative language production in children with autism. AB - The effects of specific types of adult antecedent utterances (high vs. low constraint) on the verbal behaviors produced by three subjects with autism were examined. Adult utterance types were differentiated in terms of the amount of control the adults exhibited in their verbal interactions with the subjects during a free play setting. Videotaped interactions were analyzed and coded according to a predetermined categorical system. The results of this investigation suggest that the level of linguistic constraint exerted on the child interactants during naturalistic play sessions affected their communicative output. The overall findings suggest that (a) adult high constraint utterances elicited more verbal utterances in general, as well as a majority of the subjects' echolalia; (b) adult low constraint utterances elicited more subject high constraint utterances; and (c) the degree of constraint of adult utterances did not appear to influence the mean lengths of subjects' utterances. The results are discussed in terms of their implications for educational interventions, and suggestions are made for future research concerning the dynamics of echolalia in interactive contexts. PMID- 1864827 TI - Pre- and perinatal factors in high-functioning females and males with autism. AB - Pregnancy and delivery complications as indicated in medical records and maternal reports for 23 high-functioning autistic females and 23 high-functioning males of similar IQ and age were compared with those of 54 of their normally developing siblings. Autistic subjects of both sexes had higher non-optimality scores than their siblings. Much of this difference was accounted for by a higher incidence of firstborns and fourth- or later-borns in the autistic group. Of factors found in previous research with mentally handicapped, autistic samples, only estimated weeks of gestation greater than 42 occurred more often in autistic subjects than siblings. The only sex difference specific to the autistic group was that autistic males came from larger families than females. These data provide slight support for the contribution of nonspecific pre- and perinatal factors to other etiological bases of autism. It is proposed that pre- and perinatal factors may play less of a role in autism in high-functioning individuals than suggested in studies of autism associated with severe retardation. PMID- 1864828 TI - Prediction of clinical response in children taking methylphenidate. AB - Twenty-six children having Attention Deficit Hyperactivity Disorder were tested before and after treatment with methylphenidate. In addition to standardized parent and teacher rating scales, each child was assessed on a variety of psychomotor tests with an emphasis on attentional constructs. Relatively few of the performance tests, administered prior to medication, predicted clinical response to medication. However, chronological age and performance on a memory distraction task and on the Graduated Holes Task (Klove, 1963) were moderately correlated with clinical outcome. Using stepwise multiple regression analyses to predict outcome, age and the psychomotor tasks predicted about 50% of outcome variance. There was virtually no relationship between clinical change and change on the performance tests. Findings are discussed with respect to results from previous prediction studies, theoretical models of drug response, and clinical management. PMID- 1864829 TI - Brief report: a prospective case report of infantile autism from pregnancy to four years. PMID- 1864830 TI - Brief report: competitive employment of adults with autism. PMID- 1864831 TI - Brief report: a synopsis of an open-trial of naltrexone treatment of autism with four children. PMID- 1864832 TI - Note on the relationship between population-based and clinical studies: the question of reduced optimality in autism. PMID- 1864833 TI - Autism and the use of hypnotic barbiturates in obstetrics and pediatrics. PMID- 1864834 TI - Characterization of monoclonal anti-rabbit apolipoprotein E antibodies and chemical composition of lipoproteins separated by anti-apolipoprotein E immuno affinity chromatography. AB - Six mouse monoclonal antibodies against rabbit apolipoprotein E (apo E) have been developed. Of these monoclonal antibodies, clone 5 revealed a high affinity for purified apo E, very low density lipoprotein (VLDL) and beta-VLDL. This monoclonal antibody was used to prepare an immunoaffinity column. Coupled to Sepharose 4B, this antibody allowed complete removal of lipoproteins containing apo E from plasma of New Zealand white (NZW) rabbits; 62, 46, 14, and 3% of VLDL , IDL-, LDL-, and HDL-protein, respectively, were bound to the anti-apo E affinity column. The bound VLDL was significantly rich in free cholesterol (FC) and cholesteryl esters (CE) relative to the unbound VLDL, whereas bound IDL, LDL and HDL were significantly rich in FC only. All of the bound fractions were characterized by significantly increased ratios of FC/phospholipids (PL). These results indicate that the two lipoprotein populations with and without apo E have different lipid compositions. The relatively high content of cholesterol in lipoproteins containing apo E suggests a contribution of apo E to plasma cholesterol transport. PMID- 1864835 TI - Purification and characterization of a novel thermostable lipase from Bacillus sp. AB - A thermostable lipase from Bacillus sp. has been purified to homogeneity as judged by disc-PAGE, SDS-PAGE, and isoelectric focusing. The purification included ammonium sulfate fractionation, treatment with acrinol, and sequential column chromatographies on DEAE-Sephadex A-50, Toyopearl HW-55F, and Butyl Toyopearl 650M. The purified enzyme was found to be a monomeric protein with Mr of 22,000, and pI of 5.1. The optimal pH at 30 degrees C, and optimal temperature at pH 5.6 were 5.5-7.2, and 60 degrees C, respectively, when olive oil was used as the substrate. The substrate specificity towards simple triglycerides was broad and 1- and 3-positioned ester bonds were hydrolyzed in preference to a 2 positioned ester bond. The addition of acetone to the assay mixture in the range of 0-60% (v/v) stimulated the enzyme remarkably, whereas n-hexane had an inhibitory effect. PMID- 1864836 TI - 1H NMR study on amide proton exchange of calmodulin-mastoparan complex. AB - Amide proton exchange rates of Ca2(+)-saturated calmodulin and Ca2(+)-saturated calmodulin-mastoparan complex were studied by 1H NMR spectroscopy. Exchange rates of Gly25, Gly61, Gly98, Gly134, Ile27, Ile100, and Asn137 were determined for Ca2(+)-saturated calmodulin and for Ca2(+)-saturated calmodulin-mastoparan complex, and were found to be less than 10(-4)s-1. All these residues of which the amide proton resonances appear at lower fields were considered to form hydrogen bonds, based on the results of X-ray analysis. Exchange rates of Ile27 and Asn137 became an order of magnitude smaller when mastoparan bound to Ca2(+) saturated calmodulin, while those of the four glycines and Ile100 did not change appreciably. The reduction in accessibility of Asn137 to water cased by mastoparan binding suggests that a part of the mastoparan binding site is probably located in or near the hydrophobic cluster of the C-terminal-half domain. The reduction in accessibility of Ile27 also suggests that another part of the mastoparan binding site is located in or near the hydrophobic cleft of the N-terminal-half domain. PMID- 1864837 TI - Molecular cloning and characterization of rat contrapsin-like protease inhibitor and related proteins. AB - A glycoprotein with Mr 63,000 purified from rat serum was found to inhibit trypsin activity but not chymotrypsin or elastase activity, resembling contrapsin purified from mouse serum. To obtain further information on the molecular structure, a cDNA clone (lambda CPi-21) for this contrapsin-like protease inhibitor was isolated from a rat liver cDNA library. The 1.6-kb cDNA insert contained an open reading frame that encodes a 416-residue polypeptide (CPi-21), in which the first 29 residues were suggested to comprise a signal peptide by comparison with the NH2-terminal sequence of the purified protein. The predicted structure also contained other peptide sequences determined by Edman degradation. Four potential N-linked glycosylation sites were found in the molecule, presumably accounting for the larger molecular mass of the mature form. Further screening of the cDNA library with a Pst-XbaI fragment (302 bp) of lambda CPi-21 as a probe yielded two other cDNA clones (lambda CPi-23 and lambda CPi-26), which encode 413-residue and 418-residue polypeptides, respectively. A comparison of their amino acid sequences revealed that CPi-21 has 89 and 71% homology with CPi 23 and CPi-26, respectively. The primary structure of each of the three proteins has about 70% homology with that of mouse contrapsin, in contrast to 43-46% homology with that of rat alpha 1-protease inhibitor. These results indicate that all the CPi proteins presented here belong to a subfamily of "serpins" of which mouse contrapsin was the first member to be identified. PMID- 1864838 TI - Analysis of oxygen equilibria of the giant hemoglobin from the earthworm Eisenia foetida using the Adair model. AB - Oxygen equilibrium curves of the giant hemoglobin from the earthworm Eisenia foetida were determined at various concentrations of cations. Using the Adair model of 12 oxygenation steps, we succeeded in fitting the data better than the simple concerted model (MWC model). Analysis of the Adair constants (K1 to K12) indicated that the increase in oxygen affinity occurs in the last six steps (K7 to K12) of the oxygen binding and that it is enhanced by increase in Ca2+ concentration. The Hill coefficient (nmax) at pH 7.5 attained a maximum value of 9.76 at 20 mM CaCl2. In the presence of physiological levels of Ca2+ (5 mM), the Bohr effect was similar to that seen in vertebrates. The data were consistent with the release of two Bohr protons being accompanied by the oxygen-linked binding of one Ca2+. Mg2+ and Na+ exerted a similar effect on the hemoglobin, though to a lesser extent. The stoichiometry of Ca2+ binding of the hemoglobin revealed the presence of two classes of binding sites, of which the affinities are high (Ka = 8.8 x 10(3) +/- 103 M-1) and low. The number of high affinity sites per heme was found to be 0.3, comparable to the number of oxygen-linked Ca2+ binding sites. PMID- 1864839 TI - Purification and characterization of the Escherichia coli OxyR protein, the positive regulator for a hydrogen peroxide-inducible regulon. AB - The Escherichia coli oxyR gene is required for the induction of a regulon that is inducible by hydrogen peroxide and confers resistance to oxidative stresses. We constructed a plasmid system that greatly overproduced OxyR protein and purified the protein. OxyR protein specifically bound to the upstream regulatory regions of the oxyR and katG genes as demonstrated by the gel-retardation assay and the DNase I footprinting experiment, and activated the transcription initiation of the katG gene in vitro. Using a plasmid carrying an oxyR'-'lacZ fusion gene, we studied the regulation of oxyR expression in vivo. The expression of oxyR was not induced by the treatment with a low concentration of hydrogen peroxide which induces the genes in the oxyR regulon. The expression of the oxyR'-'lacZ gene was higher in an oxyR-deletion strain than in the oxyR+ strain, and was repressed by overexpressing the OxyR protein. These results suggest that OxyR protein functions as a repressor for oxyR, in addition to its known function as a transcriptional activator for the genes in the oxyR regulon. PMID- 1864840 TI - Lysophospholipase L1 from Escherichia coli K-12 overproducer. AB - After screening 900 E. coli strains of the Clarke and Carbon collection for by lysophospholipase L1 activities, we isolated a clone bearing the plasmid pLC6-34, which showed an increased level of lysophospholipase L1 activity. Strains bearing the plasmid pC124, a subclone of pLC6-34 in plasmid vector pUC8, showed approximately 11.4 times higher lysophospholipase L1 activity than that of the parental strain. Starting from those overproducing strains, the lysophospholipase L1 was purified to near homogeneity by sequential use of ammonium sulfate fractionation, Sephacryl S-300, DEAE-cellulose, hydroxyapatite and Sephacryl S 200 column chromatographies. The apparent molecular weight of the purified lysophospholipase L1 was estimated to be 20,500-22,000 both by SDS-polyacrylamide gel electrophoresis and by gel permeation chromatography. The specific activity of the homogeneous lysophospholipase L1 was 10,400 nmol/min/mg protein when 1 acyl-sn-glycero-3-phosphoethanolamine was used as the substrate. The amino acid sequence of the amino-terminal portion of purified lysophospholipase L1 was determined and was different from that of lysophospholipase L2, which had previously been purified from the envelope fraction of E. coli strains bearing its cloned structural gene, pldB [Karasawa, K., Kudo, I., Kobayashi, T., Sa-eki, T., Inoue, K., & Nojima, S. (1985) J. Biochem, 98, 1117-1125]. The gene responsible for overproduction of lysophospholipase L1 activity was designated as pldC (phospholipid degradation C). Its restriction enzyme map was also different from that of cloned pldB. These results further confirmed that, in E. coli, there are two lysophospholipases with distinct characteristics. PMID- 1864841 TI - Papain-inhibitory activity of oryzacystatin, a rice seed cysteine proteinase inhibitor, depends on the central Gln-Val-Val-Ala-Gly region conserved among cystatin superfamily members. AB - Oryzacystatin, a cysteine proteinase inhibitor occurring in rice seeds, contains a particular glycine residue (Gly5) near the NH2-terminal position, and the sequence Gln53-Val54-Val55-Ala56-Gly57 in a central part of the molecule. Both are conserved among most members of the cystatin superfamily. We have found from Escherichia coli expression studies that the NH2-terminal 21 residues of oryzacystatin are not essential for its papain-inhibitory activity, and that the conserved pentapeptide region may be indispensable [Abe, K., Emori, Y., Kondo, H., Arai, S., & Suzuki, K. (1988) J. Biol. Chem. 263, 7655-7659]. Here we present more detailed data based on quantitative analyses of the inhibitory activities of NH2- and COOH-terminally truncated oryzacystatin and site-directed mutants at the Gln-Val-Val-Ala-Gly region. The data indicate the following results. (1) The truncated mutants lacking the NH2-terminal 21 residues or the COOH-terminal 11 residues exhibit potent papain-inhibitory activity equivalent to the activity of wild oryzacystatin. (2) However, neither the mutant lacking the NH2-terminal 38 residues nor that lacking the COOH-terminal 35 residues is completely able to inhibit papain. (3) Site-directed mutants at the Gln residue of the Gln-Val-Val Ala-Gly region have drastically reduced papain-inhibitory activities: the Gln--- Pro mutant is completely inactive and the Gln----Leu mutant has an approximately 150 times higher Ki value than wild-type oryzacystatin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864842 TI - Co-localization of immunoreactive forms of calponin with actin cytoskeleton in platelets, fibroblasts, and vascular smooth muscle. AB - Calponin is an actin binding protein found in the smooth muscle cells of chicken gizzard. The localization of the protein was examined in bovine platelets, mouse fibroblasts, and the smooth muscle cells of the bovine aorta. Immunoblotting of whole platelet lysates revealed that the antibody to chicken gizzard calponin recognized two proteins with apparent molecular masses of 37 and 23 kDa in the resting state and an additional high-molecular-weight component (approximately 40 kDa) in the activated state. The localizations of calponin and caldesmon, and the correlation of their localizations with that of the actin cytoskeleton were analyzed by immunofluorescence microscopy using appropriate antibodies and rhodamine-phalloidin. In resting bovine platelets, calponin exhibited the same distribution as actin filaments, which are organized in a characteristic wheel like structure. A similar distribution was observed with the anti-caldesmon antibody. Colocalization of calponin and actin were shown in activated platelets and along stress fibers of both fibroblasts and smooth muscle cells. These results suggest not only a cytoskeletal role associated with microfilaments but also a regulatory role of these proteins for actin-myosin interaction. PMID- 1864843 TI - An NMR study on the conformation of a deoxyoligonucleotide duplex, d(GGGGCCCC)2, and its complex with chromomycin. AB - The conformation of drug-free d(GGGGCCCC)2 and the chromomycin-d(GGGGCCCC)2 complex in aqueous solution were studied by NMR spectroscopy. The present study has indicated that free d(GGGGCCCC)2 takes the B form in solution, although it takes the A form in the crystalline state. The NMR spectrum of the complex indicated that chromomycin binds as a symmetry-related dimer to the minor groove of the central four residues of d(GGGGCCCC)2. The drastic conformational change in the central four residues of d(GGGGCCCC)2 on going from the B form family to the A form was demonstrated by the characteristic NOEs and coupling patterns. The change seems to be indispensable for accommodation of the bulky chromomycin dimer in the minor groove. On the basis of the intermolecular NOEs between chromomycin and d(GGGGCCCC)2, the structure of the complex has been constructed and refined by energy minimization. PMID- 1864844 TI - Triflavin, an antiplatelet Arg-Gly-Asp-containing peptide, is a specific antagonist of platelet membrane glycoprotein IIb-IIIa complex. AB - Triflavin, an antiplatelet peptide containing Arg-Gly-Asp, purified from Trimeresurus flavoviridis venom, inhibits aggregation of human platelets stimulated by a variety of agonists. It blocks aggregation through interference with fibrinogen binding to its specific receptor on the platelet surface membrane in a competitive manner, but it has no apparent effect on intracellular events, such as thromboxane B2 formation, phosphoinositides breakdown and intracellular Ca2+ mobilization of thrombin-activated platelets. In this study, we determined the complete sequence of triflavin, which is composed of a single polypeptide chain of 70 amino acids. Its sequence is rich in cysteine and contains Arg-Gly Asp at residues 49-51 in the carboxy-terminal domain. Triflavin shows about 68% identity of amino acid sequence with trigramin, which is a specific antagonist of the fibrinogen receptor associated with glycoprotein IIb/IIIa complex. [125I]Triflavin binds to unstimulated and ADP-stimulated platelets in a saturable manner and its Kd values are estimated to be 76 and 74 nM, respectively; the corresponding numbers of binding sites are 31,029 and 34,863 per platelet, respectively. [125I]Triflavin binding is blocked by Gly-Arg-Gly-Asp-Ser in a competitive manner. EDTA, the Arg-Gly-Asp-containing peptides (including naturally occurring polypeptides, trigramin and rhodostomin), and monoclonal antibody, 7E3, raised against GP IIb/IIIa complex, inhibit [125I]triflavin binding to unstimulated and ADP-stimulated human platelets. In conclusion, triflavin specifically binds to fibrinogen receptor associated with GP IIb/IIIa complex and its binding site is located at or near GP IIb/IIIa complex, overlapping with those of 7E3 and another Arg-Gly-Asp-containing polypeptide, rhodostomin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864845 TI - Interaction of nonpolymerizable actins with myosin. AB - Polymerization of G-actin in the presence of salt and phalloidin was blocked by treatment of G-actin with m-maleimidobenzoic acid N-hydroxysuccinimide ester (MBS) (designated as m-actin). The actin dimer produced by chemical crosslinking of F-actin with N,N'-p-phenylenedimaleimide did not polymerize and was still dimeric or tetrameric after further treatment with MBS (designated as d-actin). The m- and d-actins retained the ability to bind to myosin heads with apparent dissociation constants of 3-8 x 10(-6) and 3-5 x 10(-7) M, respectively. d-Actin formed a 1:1 actin monomer-myosin head complex. However, m-actin formed a 2:1 m actin-head complex, suggesting the presence of at least two latent actin-binding sites on a myosin head. ATP weakens only 2- to 6-fold the binding of these complexes. One of two m-actins on a myosin head was replaced by d-actin. Native F actin blocked the binding of both m- and d-actins to myosin heads in the presence and absence of ATP, although the affinities of myosin head for MBS-treated actins and F-actin are similar in the presence of ATP. These results suggest that there are at least three actin binding sites on a myosin head: one is responsible for binding of F-, m-, and d-actins, the second for binding of F- and m-actins, and the third for binding of F-actin at least in the presence of ATP. F-Actin binding to the third site may in some way block the first and second binding sites. PMID- 1864846 TI - Acyclic monoterpene primary alcohol:NADP+ oxidoreductase of Rauwolfia serpentina cells: the key enzyme in biosynthesis of monoterpene alcohols. AB - Acyclic monoterpene primary alcohol:NADP+ oxidoreductase, a key enzyme in the biosynthesis of monoterpene alcohols in plants, is unstable and has been only poorly characterized. However we have established conditions which stabilize the enzyme from Rauwolfia serpentina cells, and then purified it to homogeneity. It is a monomer with a molecular weight of about 44,000 and contains zinc ions. Various branched-chain allylic primary alcohols such as nerol, geraniol, and 10 hydroxygeraniol were substrates, but ethanol was inert. The enzyme exclusively requires NADP+ or NADPH as the cofactor. Steady-state kinetic studies showed that the nerol dehydrogenation proceeds by an ordered Bi-Bi mechanism. NADP+ binds the enzyme first and then NADPH is the second product released from it. Gas chromatography-mass spectrometric analysis of the reaction products showed that 10-hydroxygeraniol undergoes a reversible dehydrogenation to produce 10 oxogeraniol or 10-hydroxygeranial, which are oxidized further to give 10 oxogeranial, the direct precursor of iridodial. The enzyme has been found to exclusively transfer the pro-R hydrogen of NADPH to neral. The N-terminal sequence of the first 21 amino acids revealed no significant homology with those of various other proteins including the NAD(P)(+)-dependent alcohol dehydrogenases registered in a protein data bank. PMID- 1864847 TI - Hydroxylation of o-halogenophenol and o-nitrophenol by salicylate hydroxylase. AB - Salicylate hydroxylase [EC 1.14.13.1] from Pseudomonas putida catalyzed the formation of catechol from substrate analogues such as o-nitro-, o-amino-, o-iodo , o-bromo-, and o-chloro-phenol by removing the ortho-substituted groups. They are converted into nitrite, ammonia, and halide ions, respectively. Kinetic parameters of these reactions were determined by spectrophotometric and polarographic methods. Hydroxylation of o-nitro- or o-iodophenol proceeds with the unusual stoichiometry of 2:1:1 for consumed NADH, O2-uptake, and catechol formed. Other ortho-substituted phenols examined also gave the same results. Like salicylate, these substrates perturb the absorption spectrum of salicylate hydroxylase in the visible region, indicating the formation of enzyme.substrate complexes. Titration experiments with ortho-substituted phenols gave the dissociation constants of the complexes. The complexes were quantitatively reduced with NADH or dithionite without detectable formation of the intermediates. The fact that one atom of 18O2 was incorporated into the produced catechol in hydroxylation of o-nitrophenol indicates that the reaction is of monooxygenase nature. It is concluded that salicylate hydroxylase cleaves the C-N and C-X bonds of ortho-substituted phenols. PMID- 1864848 TI - A new monoclonal antibody directed to sialyl alpha 2-3lactoneotetraosylceramide and its application for detection of human gastrointestinal neoplasms. AB - A new monoclonal antibody (NS24) directed to the N-acetylneuraminyl alpha 2-3Gal beta 1-4GlcNAc residue in type II sugar chain of N acetylneuraminyllactoneotetraosylceramide [sialylparagloboside, IV3(NeuAc)nLc4Cer] was prepared by hybridoma technique. Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol, IV3(NeuAc)nLc4Cer, and lipopolysaccharides from Salmonella minnesota R595 were used for immunization with IV3(NeuAc)nLc4Cer isolated from human erythrocytes. This method allowed the fusion of spleen cells of immunized mouse with myeloma cells only three days after immunization. NS24 reacted specifically to both naturally occurring and chemically synthesized IV3-(NeuAc)nLc4Cer, whereas it has no reactivity to structurally related gangliosides, such as IV6(NeuAc)nLc4Cer, N glycolylneuraminyl alpha 2-3lactoneotetraosylceramide [IV3(NeuGc)-nLc4Cer], i active ganglioside [VI3(NeuAc)nLc6Cer], I-active ganglioside [VIII3(NeuAc) VI3(NeuAc)IV6kladoLc8Cer], GM4(NeuAc), GM3(NeuAc), GM3(NeuGc), GM1b(NeuAc), GD3 (NeuAc), other ganglio-series gangliosides, sulfatide, and paragloboside (nLc4Cer). Synthetic N-acetylneuraminyl alpha 2-3lactotetraosylceramide [IV3(NeuAc)Lc4Cer] and its asialo-derivative (Lc4Cer) carrying type I sugar chain also showed no reaction with NS24. One to 100 pmol of IV3(NeuAc)nLc4Cer was detected dose-dependently by a thin-layer chromatography/enzyme immunostaining procedure. Human gastric carcinomas showed positive reactions with NS24 immunochemically and histochemically. NS24 reacted preferentially with poorly differentiated adenocarcinomas rather than well differentiated ones. PMID- 1864849 TI - The role of plasma membrane redox activity in light effects in plants. AB - Stimulations by light of electron transport at the plasma membrane make it possible that redox activity is involved in light-induced signal transduction chains. This is especially true in cases where component(s) of the chain are also located at the plasma membrane. Photosynthetic reactions stimulate transplasma membrane redox activity of mesophyll cells. Activity is measured as a reduction of the nonpermeating redox probe, ferricyanide. The stimulation is due to production of a cytosolic electron donor from a substance(s) transported from the chloroplast. It is unknown whether the stimulation of redox activity is a requirement for other photosynthetically stimulated processes at the plasma membrane, but a reduced intermediate may regulate proton excretion by guard cells. Blue light induces an absorbance change (LIAC) at the plasma membrane whose difference spectrum resembles certain b-type cytochromes. This transport of electrons may be due to absorption of light by a flavoprotein. The LIAC has been implicated as an early step in certain blue light-mediated morphogenic events. Unrelated to photosynthesis, blue light also stimulates electron transport at the plasma membrane to ferricyanide. The relationship between LIAC and transmembrane electron flow has not yet been determined, but blue light-regulated proton excretion and/or growth may depend on this electron flow. No conclusions can be drawn regarding any role for phytochrome because of a paucity of information concerning the effects of red light on redox activity at the plasma membrane. PMID- 1864850 TI - Transplasma membrane electron transport in plants. AB - The presence of transplasma membrane electron transport in a variety of plant cells and tissues is reported. It is now agreed that this property of eukaryotic cells is of ubiquitous nature. Studies with highly purified plasma membranes have established the presence of electron transport enzymes. Two types of activities have been identified. One, termed "Standard" reductase, is of general occurrence. The other, inducible under iron deficiency and relatively more active, is "Turbo" reductase. However, the true nature of components participating in electron transport and their organization in the plasma membrane is not known. The electron transport is associated with proton release and uses intracellular NAD(P)H as substrate. The electron flow leads to changes in intracellular redox status, pH, and metabolic energy. The responsiveness of this system to growth hormones is also observed. These findings suggest a role for electron flow across the plasma membrane in cell growth and regulation of ion transport. Involvement of this system in many other cellular functions is also argued. PMID- 1864851 TI - NADH oxidase of plasma membranes. AB - NADH oxidase is a cyanide-resistant and hormone-responsive oxidase intrinsic to the plasma membrane of both plant and animal cells. The activity has many unique characteristics that distinguish it from other oxidases and oxidoreductases of both organelles and internal membranes and from other oxidoreductases of the plasma membrane. Among these are resistance to inhibition by cyanide, catalase, superoxide dismutase, and phenylchloromercuribenzoate. Activity is stimulated by hormones and growth factors and inhibited by quinone analogs such as piercidin, the flavin antagonist atebrin, and growth inhibiting gangliosides such as GM3. In marked contact to the NADH-ferricyanide oxidoreductase of the plasma membrane, the NADH oxidase is activated by lysophospholipids and fatty acids, products of phospholipase A2 action, in a time-dependent manner suggestive of stabilization of an activated form of the enzyme. The hormone-responsive NADH oxidase of the plasma membrane is not a peroxidase and may function as a terminal oxidase to link transfer of electrons from NADH to oxygen at the plasma membrane. The functional significance of the NADH oxidase of the plasma membrane is unknown but some relationship to growth or growth control is indicated. In both animal and plant plasma membranes, the oxidase is activated by growth factors and hormones to which the cells or tissues of origin have functional hormone or growth factor receptors. In addition, substances that inhibit the oxidase, the associated transmembrane reductase or both, inhibit growth. In transformed cells and tissues, the hormone and growth factor responsiveness of the NADH oxidase is reduced or absent. With human keratinocytes which exhibit an increased sensitivity to the antiproliferative action of both retinoic acid and calcitriol, the NADH oxidase of the plasma membrane is strongly inhibited by these agents and shows the same increased sensitivity. If transfer of electrons from NADH to oxygen across or within the eukaryotic plasma membrane is an important aspect of growth or growth control, then the hormone- and growth factor-responsive NADH oxidase associated with the plasma membrane could be of fundamental importance. Because of its low basal activity, stimulation by growth factors and hormones, and the inhibition of growth in direct proportion to inhibition of the oxidase, the activity is a candidate as a rate-limiting step in the growth process. Completely unknown is the mechanism whereby NADH oxidation and growth or growth control may be coupled. This, together with further characterization of the activity and the mechanism of loss of control with neoplastic transformation, represent important challenges for future investigations. PMID- 1864852 TI - [A comparison between 4 subgingival bacteriologic sampling technics]. AB - A comparative study of four classical techniques employed in the sampling of subgingival microflora (paper points, swabbing, curette and washing followed by aspiration) has been carried out. This study was based upon quantitative criteria (number of bacteria sampled) and qualitative criteria (number of morphologically distinct colonies found per sampling technique). Sampling was done on three different groups of patients: a control group, a group of patients with gingivitis and a group of patients with periodontitis. The curette sampling technique was found to be efficient both quantitatively and qualitatively. Difficulties in standardizing this method however were encountered with the failure to achieve reproducible results. For this reason the technique of paper point was preferred. This method was found to be more reliable and reproducible in each of the three groups of patients sampled. PMID- 1864853 TI - Autometallographic visualization of glycosaminoglycans in the tongue mucosa of rats using cuprolinic blue and enzymatic digestions. AB - In order to visualize by light microscopy the glycosaminoglycans (GAGs) in the rat tongue mucosa, the tissue was fixed with cuprolinic-blue (CB)-aldehyde and the staining enhanced by autometallographic (AM) procedure. As other polyanions were also detected, enzymatic digestions with hyaluronidase, chondroitinase ABC and pronase were performed on these tissues in order to test the specificity of the staining. Chondroitinase ABC caused a dramatic decrease of silver grains in the lamina propria whereas hyaluronidase and pronase induced only discrete or no modification. This supported the concept that the GAGs visualized by CB and autometallography in this area as dermatan sulphate. The other polyanions (mostly DNA and RNA) seen in the epithelial layers were unaffected by these enzyme treatments. PMID- 1864854 TI - The effect of an antimicrobial releasing varnish on root demineralisation in situ. The influence of the demineralisation period. AB - Caries in exposed root surfaces is becoming a significant problem in dentistry. Varnish applications have interesting preventive possibilities against root caries. The effect of such a varnish, containing two antimicrobials, was studied on the demineralisation of roots with a twofold aim. Firstly, the efficacy of the varnish was investigated in situ as a function of the demineralisation period. Ten participants wore sound intact roots treated with the varnish in an intra oral appliance for 2, 4 and 6 weeks. Secondly, the effect of the varnish on root demineralisation after removal of the varnish was measured. The results showed that the reduction, in demineralization of about 80% after 2 weeks, decreased in magnitude with the length of the in situ demineralisation period. After 4 weeks there was no longer statistically significant difference compared with untreated roots. The acid attack by plaque was, however, substantial in this model; after 6 weeks in situ untreated roots were so strongly demineralised that microradiography was no longer possible anymore. In the second experiment in which the varnish was removed 2 days after application there was a trend toward a reduction of about 30% in root demineralisation after 2 weeks. This was not statistically significant when compared with no application. PMID- 1864855 TI - [Oral bacterial flora and its pathogenic potential]. AB - The oral flora is a complex body formed by at least a hundred bacterial species which can be more or less regular residents in the oral cavity. Thanks to a developing taxonomy related to progress made in bacterial identification, these oral species can be separated into five groups based Gram staining and morphology: the Gram positive cocci group (Streptococcus, Staphylococcus and related geni), the Gram negative cocci group (Neisseria, Veillonella and related geni), the Gram positive bacilli group (Corynebacterium, Actinomyces, Lactobacillus, Methanobrevibacter and related geni), the Gram negative bacilli group (Haemophilus, Campylobacter, Bacteroides and related geni) and finally the spirochete group (Treponema). PMID- 1864856 TI - The effect of 2-O-stearoyl-glycerol 1,3-bisphosphate on the demineralization of dental enamel in vitro. AB - Parts of the buccal and lingual enamel surfaces of sound human third molars were treated with a test compound, and the non-treated parts served as control. After the treatment both parts were demineralized, and the artificial caries lesions were analyzed by means of quantitative microradiography. Treatment during only 1 minute with an aqueous solution of 1.5 mmol/l of the surface active compound 2-O stearoyl-glycerol 1,3-bisphosphate (Glydip) resulted in a decrease in the rate of enamel demineralization by about 60%. When Glydip was dissolved in a toothpaste/water slurry it inhibited the demineralization by about 30%. When the enamel was covered by a salivary pellicle prior to the application of the slurry, the inhibition of the demineralization disappeared. However, when Glydip was applied in an aqueous solution, the presence of a salivary pellicle did not interfere with the decreasing effect of Glydip on the demineralization. It is concluded that Glydip has promising properties for its use as an anti-caries agent, in combination with fluoride. PMID- 1864857 TI - Embryology and secretory activity of labial salivary glands. AB - This study was carried out on the heads of 20 foetuses aged between 11 and 26 weeks. Four stages were distinguished in the development of labial salivary glands, each stage corresponding to gestational age. Stage I is characterized by a localized, rounded thickening of the stomodial epiblast into the mesenchyma of the mucosal side of the lower lip. This occurs at the 9th-10th week of gestation. Stage II is reached when the epiblastic thickening assumes the form of a single cord. It is oval when sectioned transversally and is the result of the proliferation of epiblastic cells into the underlying mesenchyma during the 11th 12th week. Stage III corresponds to a branching process which takes place at the 13th week. The single cord branches to form the future secretory lobes, which rapidly assume a grape-like appearance. The number of rudimentary glands increases during the first three stages of development, i.e. as long as the first formed glands have not developed ducts. Stage IV corresponds to the process of duct formation at the 18th week. Simultaneous differentiation of acinal and duct cells is observed and this procedes the onset of secretory activity. PMID- 1864858 TI - The cellular and extracellular distribution of osteocalcin and dentin phosphoprotein in teeth of vitamin D-deficient rats. AB - Experimental and clinical data indicate that dentin mineralization is vitamin D dependent. This calcium-regulating steroid controls protein synthesis, for instance that of osteocalcin in osteoblasts. This protein also elaborated by odontoblasts was used as a molecular marker for vitamin D action on odontoblasts. Since the most characteristic protein synthesized by odontoblasts is the dentin phosphoprotein which is thought to regulate hydroxyapatite growth, its cellular and extracellular distribution was also studied. Tooth formation in the molars and incisors of successive generations of vitamin D-deficient animals (-D) and in controls (+D) was compared by microadiography, toluidine blue histochemistry, and immunocytochemistry. In -D samples, the presence of dentin phosphoprotein in odontoblasts indicated that their differentiation occurred despite major morphological disturbances at the cusp tips. In contralateral teeth, osteocalcin was depleted in odontoblasts and dentin, suggesting an inhibition of protein synthesis induced by vitamin D-deficiency. In the extracellular matrix of +D animals, phosphoprotein distribution was associated with dentin, especially within actively forming calcospherites at the mineralization front. In contrast, in -D dentin, the mineralization defects corresponded to irregular absence of histochemically detectable phosphoprotein. This protein indeed appeared either absent or uniformly sparse in -D dentin by immunocytochemistry. These data suggest that vitamin D acts directly on odontogenic cells at various synthetic (osteocalcin) or secretory (phosphoprotein) levels indicating that odontoblasts are target-cells for vitamin D. Therefore, this hormone could contribute to the regulation of extracellular mineralization during dentinogenesis, via different mechanisms in the processing of matrix protein. PMID- 1864859 TI - A rat incisor dentin matrix protein can induce neonatal rat muscle fibroblasts, in culture, to express phenotypic products of chondroblastic cells. AB - Demineralized dentin matrix induces the ectopic formation of bone, in vivo, when implanted subcutaneously or in muscle pouches. In these situations the bone induction follows a chondrogenic pathway. As part of the strategy for the assay and isolation of the factors responsible for initiating induction, we have developed a cell culture system in which the addition of soluble factors extracted from the dentin matrix appears to initiate chondrogenesis. Indicators of chondrogenesis, relative to control cultures, were taken as an increase of 35S sulfate incorporation into proteoglycan (PG), an altered size of the PG, production of type II collagen, and changes in cell morphology and matrix histochemistry. Our studies have taken two directions: the use of the cell culture system under standard conditions to select fractions inducing one or more of the above indica-tors; and, the purification and characterization of the in vitro chondrogenesis inducing factor(s). Here we report the identification of a peptide fraction which acts in culture to satisfy each of the above indicators of chondrogenesis. An EDTA extract of rat incisor dentin was fractionated by CaCl2 precipitation, Sephacryl S-100 chromatography, and reverse phase HPLC. A single peptide fraction from the HPLC, evidenced by the existence of a single spot on 2 D Gel Electrophoresis, was found to be a potent enhancer of 35S-sulfate incorporation during the standard assay, with maximal activity in the 1-10 ng/ml range. Further detailed studies showed that the heightened incorporation occurred without any increase in cell number. The neonatal rat muscle explant fibroblasts exposed to this fraction for 7 days in monolayer culture formed dense cell nodules which stained intensely with Alcian blue relative to controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864860 TI - Rates of protein turnover at specific sites of the rat incisor periodontal ligament. AB - Extraction of rat incisor periodontal ligament using neutral salt solutions was carried out on a site-specific basis following administration of 3H-labelled proline, the incorporation of 3H-proline into soluble proteins of different molecular weights was determined by SDS electrophoresis and scintillation counting. Tracer was incorporated primarily into 3 fractions with Mr = greater than 120K, 100K and 45-65K. Appearance of 3H-proline in low molecular weight components which cross-reacted with antibodies to Type 1 collagen (presumably collagen breakdown products) within 30 minutes of administration suggests a pool of collagen which is rapidly turning over. The rate of maturation of collagen from this soluble to insoluble forms may represent a level of post-translational control within the tissue which may be directly related to tissue morphostasis. PMID- 1864861 TI - An assessment of the control of matrix turnover by a quantitative ultrastructural analysis of fibroblasts of the periodontal ligament in rats. AB - A quantitative structural analysis of the synthetic and degradative organelles of fibroblasts of rat incisor and molar periodontal ligaments was conducted. The results showed that in these tissues which are reported to have significantly different rates of turnover of their functional matrix collagen the rate of synthetic activity was the same. However, there were differences in the pattern of degradation with the molar ligament having between 5 and 6 times more phagocytosed collagen than the incisor. It is suggested that post-synthesis processing may control collagen turnover rather than modulation of rates of synthesis. PMID- 1864862 TI - How osteoblasts become osteocytes: a decreasing matrix forming process. AB - Osteocyte matrix inclusion process was studied in an in vitro woven bone nodule formation model where a large number of osteocytes at different degrees of maturation were examined. This work focused on early stages of osteocyte inclusion. This matrix inclusion occurred without a matrix synthesis inversion by the future osteocyte and with maintenance of close cell contacts with the replacing cell. A passive matrix embedding process related to a decreased activity of the osteoblast-osteocyte cell is proposed as a comprehensive pathway from osteoblast to osteocyte. The formation of the osteocyte is therefore presented as a very coordinated space and time related cell-cell interaction between cells of the three cell pools of the bone. PMID- 1864863 TI - Sialoproteins of bone and dentin. AB - Osteopontin (OPN), bone sialoprotein (BSP) and bone acidic glycoprotein-75 (BAG 75), are sialoproteins isolated from bone extracts that resemble each other in size and composition. OPN and BSP contain an RGD sequence (not proven but possible for BAG-75), suggesting that their biological functions involve interaction with cell membrane integrins. Dentin has small amounts of OPN and BSP but also contains a major sialic acid-rich protein, DSP that has an overall composition similar to the bone sialoproteins. It is possible that DSP plays a similar biological role in dentin as OPN, BSP, and BAG-75 play in bone. Future experimentation should shed further light onto the potential relationships of the four sialoproteins. PMID- 1864864 TI - Calcium-binding proteins: an overview. AB - In order to understand the mechanism of the various responses evoked by calcium in the cell, the identification and characterization of a number of calcium receptors were undertaken within the past two decades. Advances in amino acid sequence and protein three-dimensional structure led to the description of two families of calcium-binding proteins, the EF-hand homolog family and the annexin family. The EF-hand motif consists of two alpha helices, "E" and "F", joined by a Ca(2+)-binding loop. EF-hands have been identified in numerous Ca(2+)-binding proteins by similarity of amino acid sequence and confirmed in some crystal structures. Functional EF-hands seem always to occur in pairs. To date, the EF hand homolog family contains more than 160 different Ca(2+)-modulated proteins which have a broad range of functions. Among them, are the calmodulin, the troponin C, the myosin regulatory light chain, the parvalbumin, the S-100 proteins and the calbindins 9- and 28 kDa. The most striking feature of the EF hand family is the ability to modulate the activity of a number of enzymes. Several groups have identified proteins from various tissues that show calcium dependent binding to membranes. These proteins, termed annexins have a molecular weight of 35- or 67 kDa. The amino acid sequences of the members of the annexin family show that each protein contains conserved internal repeats of about 70 amino acids each. The 35 kDa annexins contain four repeats, which show a high degree of homology with each other and with the repeat sequences of the other proteins. These repeats correspond to structural domains with a similar fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864865 TI - Immunolocalization of a 110 kD molecule and a 150 kD molecule in rat incisor and mandibular bone. AB - In the present study, antibodies against rat dental proteoglycans were used to characterize and localize the proteoglycans in rat incisor and mandibular tissues. Polyclonal rabbit antibodies were raised against a CPC-precipitated fraction of a sulfated dental extract. In unpurified dental extract these antibodies recognized two molecules of 110 kD and 150 kD. The 150 kD molecule was susceptible to chondroitinase ABC digestion but the 110 kD molecule resisted this enzymatic degradation. Immunocytochemically these two molecules were seen to be located in the pulp, the enamel organ and the mandibular bone. In each tissue only the periphery of the cells was stained and not the intracellular compartment. In the mineralized area of bone, dentin and forming enamel no staining was seen. These results indicate common epitopes in the proteoglycans from pulp, predentin, enamel organ and bone. Some differences were found in the nature of tooth and bone proteoglycans. PMID- 1864866 TI - Surgical management of extracranial vertebral artery occlusive disease. AB - Thirty-seven consecutive patients underwent vertebral artery (VA) reconstruction over a 6 years period (1983-1989). Detailed neurologic, medical, and angiographic information was obtained for all patients. Indications for surgery were as follows: (1) stenosis of VA with symptoms of vertebrobasilar insufficiency; (2) very tight stenosis (greater than 75%) of the dominant VA with stenosis or occlusion of the contralateral VA; (3) very tight stenosis of VA with bilateral occlusion of the internal carotid artery (ICA); (4) very tight stenosis of VA with homolateral ICA lesion eligible for simultaneous repair; (5) very tight stenosis of VA and very tight stenosis of the homo or contralateral carotid siphon. There were 15 isolated vertebral lesions (group I), and 22 were VA lesions associated with lesions of the supraaortic trunks which were simultaneously treated (group II). The reconstructions of the first portion of the VA were 30 (12 of group I and 18 of group II) and reimplantation of the VA into the common carotid artery was the procedure of choice. There were 7 revascularizations of the third portion of the VA at C1-C2 level (3 of group I and 4 of group II): carotid-vertebral bypass, using an autogenous vein graft, was the procedure of choice. Three patients in group II died in the immediate postoperative period from myocardial infarction but no patient presented immediate postoperative neurologic deficits. All symptomatic patients but one were relieved of their symptoms in a median follow-up of 31 months. No postoperative complications were observed. Long-term results were satisfactory in all the 28 patients at their last follow-up visit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864867 TI - Clinical follow-up and progression of carotid atherosclerosis determined by duplex scanning in patients suffering from TIA. AB - We investigated the clinical outcomes and the progression of the internal carotid arterial lesions of a group of patients presenting with hemispheric TIAs. The cumulative frequency of TIAs during a mean follow-up period of 40 +/- 14 months was 14%, and no relationship was found between new TIAs and the presence of known cardiovascular risk factors or plaque characteristics as determined by duplex scanning. With the exception of one patient who died of stroke, none of the patients developed a permanent neurologic deficit. The cumulative death rate was 6.5%; myocardial infarction was the most common cause (3 out of 7). Anatomic progression of plaques was determined by duplex scanning in 22% of the internal carotid arteries. No relationship between progression of these plaques and the development of new TIAs was evident. We conclude that, in this group of patients, TIAs do not inevitably lead to stroke and that TIAs are not predictable based on risk factors or plaques characteristics. PMID- 1864868 TI - Resection and reconstruction of the carotid bifurcation with polytetrafluoroethylene grafts; operative technique. Preliminary results in 25 procedures and indications. AB - Although carotid endarterectomy is the standard procedure, the purpose of this paper is to describe a new surgical technique and indicate its role in the surgery of cervical cerebrovascular disease. The technique consists of resection of the pathologic carotid artery bifurcation followed by its total replacement with a bifurcated thin-wall polytetrafluoroethylene (PTFE) graft constructed by the surgeon. Prosthetic graft reconstruction of the carotid bifurcation (PGRCB) was performed in 21 patients (25 procedures) from November 1984 to May 1987. Many patients were over 70 years old. The indications for surgery were transient ischemic attacks (TIA)'s in 10 patients (high-grade stenosis), established stroke with mild deficit in 3 patients (high-grade stenosis). Eight patients (high-grade stenosis) were asymptomatic and 4 had vertebro-basilar symptoms. In 11 procedures the indications were the same as for standard carotid endarterectomy (significant stenosis and/or ulcerated plaque). In 14 cases, the procedure was justified by extensive lesions involving a long segment of the internal carotid artery (2 restenoses, 12 calcified lesions). In the perioperative period, there were no deaths and no TIA's. The 25 procedures were assessed one month postoperatively by ultrasonic imaging and venous substraction angiography. All the grafts were patent with perfect restoration of the carotid bifurcation anatomy. Systematic follow-up study was carried out in 1987. Three patients had died of non neurologic causes and one was lost to study. The remaining 19 procedures were evaluated with an average follow-up of 19 months (range 7 to 32 months). The patients were asymptomatic and all the grafts remained patent including one stenosis (greater than 50%) at the common carotid artery anastomosis. Because recent studies have documented a much higher rate of technical defects or recurrent stenosis after carotid endarterectomy, we believe that PGRCB merits consideration, particularly in difficult endarterectomies, and in recurrent carotid stenosis. Furthermore it seems acceptable to advocate PGRCB in aneurysms of the internal carotid artery and in post-irradiation arteritis. PMID- 1864869 TI - General moderate hypothermia in the surgical treatment of descending thoracic aortic aneurysms. AB - The diagnosis and surgical treatment of aneurysms of the descending thoracic aorta is difficult and some aspects of management remain controversial. We report 53 patients treated in the period 1983-1988; 25.9% of them had previously been erroneously diagnosed as having mediastinal cysts or tumours. Duplex scanning and computerised tomography were valuable adjuncts in establishing the correct diagnosis, which was confirmed by aortography in 52 patients. Of 49 patients operated upon electively three died with a mortality rate of 6.1%; of the 4 patients operated upon as emergencies 2 died. Fifty patients survived the operative procedure and of the 3 operated upon under normothermia 1 developed paraplegia, whereas of the 47 patients operated upon under moderate hypothermia (30 degrees-31 degrees C) only 1 developed paraplegia. PMID- 1864870 TI - Descending thoracic aortofemoral bypass as an alternative for aortoiliac revascularization. AB - We performed descending thoracic aorta to femoral bypass in six selected patients over the past four years. An alternative inflow source was selected because the standard transabdominal approach was contraindicated or considered hazardous. The inflow consisted of a single Dacron tube from the descending thoracic aorta to the left groin, and a femorofemoral bypass to the right groin. There was no operative mortality or major morbidity related to the surgical procedure. After an average follow-up of 17.1 months (range 6 to 23 months), all thoracofemoral grafts remained patent. One patient had repeated occlusions of the femorofemoral graft related to right lower extremity outflow disease, while the remaining five crossover grafts are patent. One patient died 22 months postoperatively from a myocardial infarct, with a patent bypass. Although this series represents a small group of patients, we feel that descending thoracic aortofemoral bypass offers excellent inflow and reliable patency, and is a good alternative when reoperation on the abdominal aorta is undesirable. This procedure may also be considered for conversion of an axillofemoral bypass that has failed repeatedly. PMID- 1864871 TI - Hydronephrosis after aortofemoral bypass graft. A prospective study. AB - This prospective study was designed to determine the frequency and natural history of hydroureteronephrosis (HUN) after placement of an aortobifemoral vascular graft. A total of 30 patients were evaluated by the study protocol, which included: pre and postoperative biological kidney function tests, preoperative and early postoperative (14th day) intravenous pyelograms and a late (mean 18th month) urologic examination by renal ultrasonic tomography. Four asymptomatic, early cases of HUN were observed in the 57 ureters examined (7%); all four complications regressed in less than 30 days. No cases of symptomatic early or late HUN were observed in this series. Asymptomatic early HUN was a frequent complication in our series (7%) but its benign course does not justify systematic screening. These asymptomatic complications contrast with the symptomatic cases of early or late HUN reported in the literature which necessitated urologic and vascular investigations. PMID- 1864872 TI - Ischemic complications of abdominal aortic surgery. AB - From 1982 through 1988, 634 consecutive patients underwent abdominal aortic reconstruction for occlusive (37%) or aneurysmal (63%) disease. We studied the ischemic problems affecting the branches of the aorta, excluding the coeliac and superior mesenteric arteries. Ischemic colitis (0.6%), spinal cord ischemia (0.16%), renal insufficiency (17%), and lower limbs ischemia (6.5%) were the major problems encountered. We identified the most significant factors associated with these complications such as hypotension, emergency, hypovolemia, preoperative renal function, suprarenal clamping, the quality of the preoperative investigation, and have suggested some specific preventive measures. PMID- 1864873 TI - Rehabilitation potential of elderly patients with major amputations. AB - This study was undertaken to determine the rehabilitation potential of patients undergoing amputation for vascular disease. A total of 101 patients were studied with a mean age of 69 +/- 14 years, 26 of whom were over age 80. Operative indications were gangrene or ulceration in 80% with rest pain in 20%. Eighteen patients were bilateral amputees. Fifty per cent of the patient population had previous vascular operations. The operative mortality was 13% and was not affected by the age of the patients or the presence of diabetes. Most operative deaths were due to cardiac or septic respiratory complications. Twenty-four of 88 surviving patients were not considered candidates for rehabilitation and the major determining factor was the occurrence of a remote or perioperative stroke. None of these 24 patients was discharged from institutional care. Sixty-four patients were considered rehabilitation candidates with equal distribution in all age groups. Ninety-five per cent of these patients were discharged home with 80% of those patients over 80 being discharged. Eighty-seven per cent of the elderly rehabilitation candidates were fitted with prostheses which compares favourably to other age groups. Seventy-three per cent of the elderly reached their rehabilitation goals (most frequently ambulation with the aid of a walker) which is only slightly less than the younger amputation group. From this study we conclude that amputations which are done for ease of nursing care and patient comfort in debilitated patients have a high mortality rate and rehabilitation goals are unlikely to be met. We have demonstrated high success rates with rehabilitation including patients over age 80. The majority of these patients may be discharged home after a period of aggressive rehabilitation. PMID- 1864874 TI - Arterial injuries. Review of 12 years experience with 32 patients. AB - Thirty-two patients with 41 injured arteries were operated upon during a period of 12 years. Three quarters were men, and the median age was 33 years. Accompanying lesions were seen in 87.5% of the patients. Nearly half the lesions were related to blunt trauma. Occupational accidents constituted the largest group. The diagnosis was made on clinical grounds in most cases. The median time lapse from trauma to operation was 5 hours. The principles of treatment were those that are generally accepted. No patients died, the amputation rate was 12.5%. Median follow-up was 8 months. A successful arterial reconstruction contributed to a good functional result. Postreconstruction thrombosis of arteries were found to occur within the first hours or days after reconstruction. Late thrombosis was rare and the overall long-time patency was 61.4%. Patency of repair of upper limb small vessels was 54.5%. PMID- 1864875 TI - Clostridial mycotic aneurysm of the suprarenal abdominal aorta. AB - Clostridial mycotic aneurysms are unusual. We therefore record a fatal case of a ruptured clostridial mycotic aneurysm of the suprarenal aorta which developed several weeks after the resection of a segment of gangrenous small bowel. PMID- 1864876 TI - Recurrent aortic graft infection following descending thoracic aorta to femoral artery bypass. A case report and review. AB - This paper presents a patient who developed a recurrent aortic graft infection after a descending thoracic aorta to femoral artery bypass. The patient had previously undergone successful management of an infected aortobifemoral bypass by removal of the graft and revascularization of the lower extremities with axillofemoral bypasses. A general discussion of the management of infected aortic grafts is presented and a discussion of the management of this particular patient is presented in detail. PMID- 1864877 TI - Popliteal aneurysm with spontaneous arteriovenous fistula. AB - This report documents a rare manifestation of aneurysmal disease of the popliteal artery. We describe a popliteal aneurysm presenting with acute venous hypertension due to a spontaneously occurring arteriovenous fistula. The fistula was defunctionalized by treating the aneurysm with a standard technique of exclusion and bypass with resolution of the symptoms of venous hypertension and maintenance of normal distal perfusion. PMID- 1864878 TI - Physiologic and pathologic evaluation of chronic extra-aortic counterpulsation with latissimus dorsi flap. Preliminary results. AB - This study attempted to evaluate the efficacy of chronic extra-aortic counterpulsation with a latissimus dorsi neuro vascular flap. Five dogs had a preliminary procedure consisting of the creation of a latissimus dorsi flap and a thoracotomy in which the flap was wrapped around the descending aorta just distal to the left subclavian artery. An epicardial lead was placed on the left ventricle and a nerve stimulating lead placed around the thoraco-dorsal nerve. Three weeks later, both leads were connected to a cardiomyostimulator programmed to function in a counterpulsation mode with a 1:2 assist frequency. Hemodynamic measurements were made at 6 and 8 and 10 and 12 weeks and the dogs were sacrificed. Three dogs had all sets of hemodynamic measurements made. Two of the three dogs demonstrated diastolic augmentation at 6 and 8 and 10 and 12 weeks average 20 to 25 mmHg. The third dog failed to demonstrate any change. All dogs were sacrificed at 12 weeks and specimens were submitted for histologic evaluation. The muscle flap was preserved in all animals. The aorta subjacent to the flap showed, (1) normal intima with no evidence of disruption or thrombus in all animals, (2) in the animals in whom counterpulsation was observed, there appeared to be thinning of the media in the aorta subjacent to the muscle flap, and (3) no evidence of distal emboli. This study demonstrated that chronic counterpulsation can be obtained with a latissimus dorsi flap. The actual hemodynamic benefits are not determined from this study. The medial thinning in the aortic wall may limit the long-term benefit of this procedure. PMID- 1864879 TI - A "twilight period" of coronary perfusion: the risk of intraoperative infarction in surgery for main left coronary obstruction. AB - This study investigates the significance of an intraoperative period of low coronary perfusion pressure which may lead to ischemia, infarction, or both, in patients undergoing coronary bypass surgery for tight left main obstruction. "Twilight Period" (TP) was defined as the time interval from initiation of cardiopulmonary bypass to implementation of cold cardioplegia. Fifty-four patients with main left coronary obstruction (greater than 50%) were divided in three groups: Group I (20), TP less than 5 minutes; Group II (15), TP = 5-15 minutes; and Group III (19), TP greater than 15 minutes. Monitoring parameters included: systemic perfusion pressure during TP, perfusion flows, length of TP, time of ischemia, myocardial temperatures during ischemia, postoperative CK-MB level, EKG-detectable infarction, and postoperative therapeutic support requirements. RESULTS: Intraoperative myocardial infarction by EKG was 0% in Group I, 7% in Group II, and 26.3% in Group III; mortality was 0%, 0%, and 15.7%, respectively. CK-MB values were 18 +/- 3.2 IU, Group I; 18.3 +/- 2.5 IU, Group II; and 49.4 +/- 10.3 IU, Group III. Group I vs. III: P 0.01. Levels of postoperative support: Level A, less than 12 hours; Level B, 12-36 hours; and Level C, greater than 36 hours. Intra-aortic balloon pump (IABP) was considered Level C. In Group I, 75% (15/20) fell in Level A; 15% (3/20) in Level B and 10% (2/20) in Level C. In Group II, 60% (9/15) fell in Level A; 26.7% (4/15) in Level B; and 13% (2/15) in Level C. In Group III, 36.8% (7/19) fell in Level A; 15.8% (3/19) in Level B; and 47.4% (9/19) in Level C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1864880 TI - Age-related complications and optimal choice of artificial heart valves in elderly patients. AB - The use of bioprosthetic heart valves in elderly patients is presently advocated by many since implanting mechanical valves are considered to result in unacceptable rates of thromboembolism and bleeding. However the somewhat limited durability of bioprostheses has to be acknowledged since a group of elderly patients will eventually require a reoperation due to tissue failure. We have evaluated our policy to implant mechanical heart valve prostheses even in elderly patients based on the conception that we believe that anticoagulation in this group of patients can be handled with a low rate of complications. PMID- 1864881 TI - Paraprosthetic leak: a complication of cardiac valve replacement. AB - Paraprosthetic leak (PPL) is a rare but potentially serious complication of cardiac valve replacement. Between 1974 and 1988, 1175 prosthetic valves were implanted in 1026 patients by one cardiac surgeon at St. Thomas' Hospital, London. Of these 539 (52.5%) were aortic (AVR), 334 (32.6%) mitral (MVR), 7 (0.7%) tricuspid, and 144 (14%) AV and MV double valve replacements (DVR). There were only 2 triple valve replacements. The prosthetic valves implanted were the Starr-Edwards (7%), Bjork Shiley (11.8%), Lillehei-Kaster (23%), Carpentier Edwards bioprosthesis (35.2%), Duromedics bileaflet (16.4%) and a variety of other mechanical and bioprosthetic valves (6.6%). Over the 15 year period there were a total of 82 (7%) valve failures of which PPL was diagnosed in 29 (2.5%) valves in 24 patients. Presenting features included cardiac decompensation in 72%, bacterial endocarditis in 12% and haemolytic anaemia in 12%. One patient (4%) had no symptoms. Nineteen patients underwent re-operation. Median time to re operation was 15 months (range 1-65 months) with a re-operative mortality of 22%. Clinical evidence of prosthetic valve infection was found in 79% of MVR and 67% of AVR. A heavily calcified aortic annulus, found in 47% of patients, may also have contributed to PPL after AVR. PMID- 1864882 TI - Clinical results of mitral valve replacement with and without preservation of the posterior mitral valve leaflet and subvalvular apparatus. AB - In this study we attempted to investigate the importance of posterior leaflet preservation during mitral valve replacement (MVR). One hundred and forty randomly selected patients with isolated mitral insufficiency were studied, half of whom had MVR with preservation of the posterior leaflet (Group I), whereas in the other half conventional MVR was performed, without preservation of the posterior leaflet (Group II). Within these two groups there were no in hospital deaths, but 5 patients in Group II were admitted to the hospital with congestive heart failure and 3 of them died after approximately 6 months. Long term mortality rate was 4.2% in Group II. Ejection fraction (EF) decreased postoperatively from 56% to 50% in Group I (p less than 0.05), and from 59% to 49% in Group II (p less than 0.05). Fifteen patients in each group and aged below 30 with sinus rhythm and in the first functional capacity according to the New York Heart Association classification (NYHA) were subjected to exercise study, 18 months after the operation. After exercise EF increased from 47% to 64% in Group I and decreased from 51% to 47% in Group II. These findings suggested that MVR with the preservation of the chordae tendineae can be done with a low morbidity and mortality rate in the early and late postoperative period. PMID- 1864883 TI - Changes in the serum levels of CK-MB, LDH, LDH1, SGOT and myoglobin due to cardiac surgery. AB - Elevation of serum levels of enzymes due to myocardial necrosis is considered to be a specific finding for myocardial infarction. This study was designed to determine the changes in the levels of LDH, SGOT enzymes, LDH1, CK-MB isoenzymes and myoglobin in patients who have had coronary bypass grafting and who have had atriotomy for surgical correction without any evidence of myocardial infarction diagnosed by clinical, hemodynamic and electrocardiographic findings. It was found that CK-MB, LDH, LDH1 and myoglobin showed significant elevations which mimicked a perioperative myocardial infarction. SGOT also increased, but remained within the normal range. CK-MB, LDH and LDH1 increased more in the coronary bypass grafted patients whereas myoglobin increased in the patients who had atriotomies. It was concluded that in order to demonstrate a perioperative myocardial infarction it is necessary to determine at least two of these enzymes for a long period and to correlate these results with the clinical, hemodynamic and electrocardiographic findings. PMID- 1864884 TI - Intestinal ischemia associated with cardio-pulmonary-bypass surgery: a life threatening complication. AB - Intestinal ischemia following open heart surgery is rare but nevertheless extremely dangerous and the causes are still unclear. The purpose of this study was to evaluate the factors influencing the occurrence and outcome of patients with this complication. At our institution between 1985 and 1989 1712 patients underwent open heart surgery and 4 female patients suffered from intestinal ischemia. The early mortality was 2.5% for the whole group and 100% for the group with intestinal ischemia. All these 4 patients were elderly and had a history of hypertension and hyperlipoproteinemia. Three of the four patients with intestinal ischemia had various risk factors for thromboembolic events such as pre-existing occlusive arterial disease and cardiac dysrhythmias or had a complicated postoperative course. In two patients an enormous increase in serum lactate to over 10 mmol/l occurred prior to the intestinal ischemia. We therefore consider advancing age, female gender and a susceptibility for thromboembolic events as important risk factors for the development of intestinal ischemia. A serum lactate over 10 mmol/l should lead to an aggressive diagnostic and therapeutic approach including exploratory laparotomy. PMID- 1864885 TI - Myocardial echinococcosis with perforation into the pericardium. AB - Though rare, cardiac echinococcosis should be included in the differential diagnosis of cardiac tumors, particularly in patients originating from endemic areas or with manifestation of hydatid disease in other organs. Diagnosis and localisation of the cysts is best accomplished with non-invasive methods such as 2-D transthoracic and transesophageal echocardiography, computed tomography and NMR. Excision of the cardiac cyst from the interventricular septum in a 21 year old patient with polyvisceral echinococcosis was performed with cardiopulmonary bypass. Adjunctive medical therapy with mebendazol is being continued for 24 months postoperatively. Twelve months after surgery the patient is asymptomatic without echocardiographic signs of recurrence. PMID- 1864886 TI - Hemopericardium: a late complication after repair of pectus excavatum. AB - Hemopericardium and tamponade occurred in a 12 year old boy with Marfan's syndrome, two years after surgical repair of pectus excavatum. This life threatening complication resulted from penetration of a fractured metal plate through the pericardium into the right atrium. The clinical details are reported and discussed. PMID- 1864887 TI - Interrupted aortic arch with tetralogy of Fallot. A report of an unsuccessful surgically treated case. AB - Interrupted aortic arch is a complete discontinuity of two segments of the aorta. Although associated with a number of conditions, it does not occur in association with pulmonary stenosis. We report a case unsuccessfully treated but from which we have learnt a lesson. PMID- 1864888 TI - A simple method of scapular retraction for posterolateral thoracotomy. AB - A simple method of scapular retraction for posterolateral thoracotomy is presented. This technique allows for retraction and stabilisation of the scapula and prevents it from protruding over the intercostal space chosen for entry into the chest cavity. It also facilitates insertion of the chest retractor and spreading of the intercostal space since reduced tension is now exerted on the rib cage by the retracted scapula and muscle layers. PMID- 1864889 TI - Annotation: the analysis of change in longitudinal studies of development. PMID- 1864890 TI - The Emanuel Miller Memorial Lecture 1990. Cooperative learning in classrooms: processes and outcomes. AB - This article focuses on the description and analysis of our research on cooperative grouping over the last 8 years. This research effort has moved through three interconnected phases--from description of classroom practice, to experimentation, to implementation. Descriptions of typical classroom practice have established the paucity of cooperation. Groups tend to be no more than collections of children sitting together but engaged on individual work. In such groups the level of cooperation, frequency of explanations and knowledge exchange is low. Thus, in order to gain an understanding of the nature and process of cooperation in groups on normal curriculum tasks required the setting up of within-classroom experiments. These revealed, among others, that group composition is important to learning outcomes, and that pupil involvement substantially improves in cooperative group endeavours. Missing, however, were data on the successful implementation of cooperative groups. Yet successful implementation has great contemporary relevance because of the demand for assessed skills in collaboration in the national curriculum. Our current work therefore addresses the impact of changing grouping practices on group processes, classroom management, the teacher's role and children's learning. Preliminary findings from this study are presented together with a wider analysis of the state of the research field and possible ways forward. PMID- 1864891 TI - Social-emotional predictors of preschoolers' responses to adult negative emotion. AB - The study examined predictors of children's prosocial responses to adult negative emotions. An adult displayed anger, sadness and pain during play sessions with 39 preschoolers (mean age = 43 months). Older children responded more prosocially to all three emotions, whereas children with greater emotion knowledge responded more prosocially to the adult's sadness. Children who behaved prosocially in response to peers' negative emotions also were prosocial after the adult's negative emotions, even with effects of age and emotion knowledge held constant. Assertive children responded more prosocially to the adult's anger, even with effects of other variables held constant. Both theoretical and practical implications are discussed. PMID- 1864892 TI - Risk indicators: assessment of infancy predictors of pre-school behavioural maladjustment. AB - The prediction of later outcome from factors present in infancy has been an ongoing concern, with difficult temperament frequently being posited as one important risk factor. Using data from a longitudinal study of a large representative sample of children, and a categorical approach to analysis, a set of infancy risk factors covering within-child, environmental and relationship variables was related to behavioural and emotional adjustment at 4-5 years. Single risk factors, including difficult temperament, resulted in only modest increases in the prevalence of later maladjustment. However, certain combinations of risk factors were associated with markedly increased prevalence rates. The results indicate the cumulative effects of risk factors, and the need to consider temperament within a contextual framework. PMID- 1864893 TI - Child and parent perceptions of the upsettingness of major life events. AB - An adaptation of the Coddington Social Readjustment Rating Scale for use with first-grade children was administered to 164 first-graders and their parents. Parents indicated whether each event occurred and both parents and their children rated the upsettingness to the child. Parent ratings of stress are significantly higher than child ratings for specific events and a composite stress measure. Parent and child composite scores correlated 0.21 when the number of events was controlled. Implications for research on life events and childhood stress are discussed. PMID- 1864894 TI - The development of psychological well-being in late adolescence. AB - Studies following adolescents from school to work indicate a sharp decrease in psychological symptoms over the 16-17-year period compared to a more gentle decrease subsequently. This could be a genuine developmental phenomenon, related to school leaving, or because anxiety levels are higher at age 16 years due to approaching examinations. The present study examined these hypotheses. GHQ scores for those at school were related to examination candidacy. Eighteen months later such differences had disappeared among those young people now in full-time employment. Similarly, a group who remained in full-time education also showed a significant decline in GHQ scores. PMID- 1864895 TI - Adult attitudes toward over- and undercontrolled child problems: urban and rural parents and teachers from Thailand and the United States. AB - In a study of adult attitudes, urban and rural parents and teachers in Thailand and the U.S. made judgments about two children, one with overcontrolled problems (e.g. shyness, fear), one with undercontrolled problems (e.g. disobedience, fighting). Consistent with previous literature, Thais (vs Americans) rated problems of both types less serious, less worrisome, less likely to reflect personality traits, and more likely to improve with time. Urban-rural differences and parent-teacher differences had negligible impact. The findings suggest that certain cultural differences in adult attitudes toward child problems may be robust across parents and teachers and across urban and rural settings. PMID- 1864896 TI - The use of questionnaires in child psychiatry research: measuring their performance and choosing an optimal cut-off. AB - This paper introduces the basic principles of Receiver Operating Characteristics (ROC) analysis, a technique to evaluate and compare the discriminant power of questionnaires employed in psychiatric research. ROC curves may assist in the selection of an optimal cut-off point, which has been shown to depend upon the prevalence rate, the consequences of correct and incorrect classifications, and the distributions of scale scores among normal individuals and cases. Then, ROC analysis is applied to the Child Behavior Checklist on a sample of 564 6-11-year old French children. The performances of the social competence scales of this instrument are poorer than those of the behavior problem scales. The findings suggest also that the cut-offs should be varied within this same age group and be higher for screening in community surveys. Further applications of ROC analysis are discussed. PMID- 1864897 TI - Chromosomes in anorexia nervosa. A study of 47 cases including a population-based group: a research note. AB - Forty-seven cases with anorexia nervosa (including a total population group) and 47 sex-, age-, and school-matched comparison cases were subjected to chromosome analyses in a blind fashion. No major abnormalities were found in any of the cases. Sex chromatin was analysed in buccal smears from the girls. No differences between the anorexia nervosa and the comparison cases were found. It seems that chromosomal/sex chromatin analyses in anorexia nervosa are not warranted. PMID- 1864898 TI - IQ similarity in monozygotic and dizygotic twin children: effects of the same versus different examiners: a research note. AB - The Wechsler Intelligence Scale for Children--Revised was administered to two independently identified samples of monozygotic (MZ) and dizygotic (DZ) twin children. Co-twins in the first sample were tested by the same examiner, while co twins in the second sample were tested by different examiners. IQ intraclass correlations were similar for the two MZ twin samples (.84 and .88), and identical for the two DZ twin samples (.54). The implications of this analysis are discussed with reference to twin study methodology, research on IQ similarity and replication of child development research. PMID- 1864899 TI - Use of chromatofocusing for separation of beta-lactamases. IX. Analytical chromatofocusing for the separation of a chromosomal cephalosporinase from Proteus vulgaris 1028. AB - Simultaneous purification and isoelectric point (pI) determination was carried out at analytical scale of the chromosomal cephalosporinase from the Proteus vulgaris 1028 strain. Comparison of the enzyme to the purification results with m aminophenylboronic acid-agarose affinity chromatography with sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed that minute amounts of accompanying proteins having identical pI values but different molecular masses were found in the chromatofocused preparation. The molecular mass of the enzyme was 24,000 dalton. The pI was found to be 8.3. PMID- 1864900 TI - Separation of ribosomal subunits on Trisacryl GF 2000. AB - The separation of rat liver and E. coli ribosomal subunits was attempted on Trisacryl GF 2000. Contrary to experiments with Sepharose 4B and Bio-Gel A-15 the 60S mammalian subunit did not bind to the resin at 4 degrees C but eluted within the column volume ahead of the 40S subunit. Puromycin, however, used to prepare the subunits, which on the agarose gels had eluted at the total column volume, exhibited anomalous retardation on the Trisacryl resin. Trisacryl therefore behaves as the more non-polar resin, and the binding of 60S subunits to agarose gels is a result of hydrophilic interaction. PMID- 1864901 TI - Quantification of methyl farnesoate levels in hemolymph by high-performance liquid chromatography. AB - Methyl farnesoate (MF) is an acyclic sesquiterpenoid that has been detected in hemolymph and other tissues of crustaceans and insects. This paper describes a rapid and sensitive method for measuring MF in crustacean hemolymph. Extracts of hemolymph samples were separated by normal-phase high-performance liquid chromatography (5-microns silica, 250 x 4.6 mm I.D., 1.3% diethyl ether in hexane) and detected by UV (220 nm). The limit of detection with this method was less than 250 pg/ml. This method should be useful for studying the physiological functions of MF in crustaceans and other arthropods. PMID- 1864902 TI - Separation and purification of oligonucleotides using a new bonded-phase packing material. AB - We describe a new bonded-phase packing material, based upon surface-stabilised microparticulate silica, suitable for the rapid separation and purification of oligonucleotides. Columns packed with this material were demonstrated to give rapid separations of individual oligonucleotide species of up to 44 base units with high purity; agarose gel electrophoresis showed that the products were essentially single bands, with only trace quantities of the (n-1)-mer present. Baseline resolution of the desired oligomer from (n +/- 1)-mer was achieved under preparative loading conditions, where up to 200-300 micrograms of oligonucleotide could be separated. The separation was essentially independent of structure or sequence of the oligonucleotides. The retention mechanism of the oligonucleotides was investigated, and the results used to determine the optimum column configuration and separation conditions. PMID- 1864903 TI - Optimized high-performance liquid chromatographic procedure for the separation and determination of the main folacins and some derivatives. II. Extraction method and application to rat liver. AB - Different methods for the extraction of folacins from biological materials and the hydrolysis of pteroylpolyglutamates prior to high-performance liquid chromatography were investigated. Acetone precipitation of proteins led to higher extraction rates of folates from biological materials as examined by using an endogenous labelling technique. It also caused less destruction of some folates but could not be combined with subsequent hydrolysis of pteroylpolyglutamates. Pteroylpolyglutamates were hydrolysed by a partially purified suspension of pteroylpolyglutamates hydrolase (PPH). Comparative studies on the folate content of rat liver revealed that complete hydrolysis of polyglutamates could also be achieved by incubating the homogenized tissue at 37 degrees C to allow endogenous PPH to act. This procedure causes interconversions of folates and is therefore not suitable for the analysis of biological materials. PMID- 1864904 TI - A PCR membrane spot assay for the detection of plum pox virus RNA in bark of infected trees. AB - A procedure for sensitive detection of plum pox virus RNA in infected bark of trees is described. The method is based on the extraction of bark material with buffer containing proteinase K followed by partial purification of RNA using QUIAGEN anion exchange resin. The RNA is then reverse transcribed, the single stranded cDNA is amplified by the polymerase chain reaction using biotinylated deoxynucleotides as label. The amplified cDNA can subsequently be detected by spotting the reaction mixture onto a nitrocellulose membrane. After fixation and washing the incorporated label is detected enzymatically using streptavidin alkaline phosphatase. It was shown that this non-radioactive detection system is more sensitive than ELISA and a DNA/RNA hybridization test using 32P-labelled probes. It is also possible to detect plum pox virus infection with this assay in trees in the non-vegetative period. PMID- 1864905 TI - A new virus isolate from infectious hypodermal and hematopoietic necrosis virus (IHHNV)-infected penaeid shrimps. AB - A new virus was isolated from infectious hypodermal and hematopoietic necrosis virus (IHHNV)-infected penaeid shrimps. The virus was isolated from two species of penaeid shrimps obtained from three different sources employing a previously developed cell-culture assay. Electron-microscopical studies of both purified virus and infected cells showed bullet-shaped particles identifying it as a rhabdovirus. PMID- 1864906 TI - Method for the concentration of infectious pancreatic necrosis virus from hatchery water. AB - A method was developed for concentrating infectious pancreatic necrosis virus from hatchery water using positively charged 1-MDS filters. The method consists of passing large volumes (Ca. 1001) of hatchery water through 1-MDS microporous filter followed by the elution of the adsorbed virus using a high pH buffer. The virus adsorbed efficiently to 1-MDS filters when the pH of the water was 5.5 and was eluted optimally with 3% beef extract solution (pH 10). This procedure permitted the processing of 100 1 of hatchery water which resulted in a 300-fold reduction in the volume of water and greater than 90% recovery of the seeded virus. PMID- 1864907 TI - Rubella-specific IgG1 avidity: a comparison of methods. AB - Two methods of determining the avidity of specific IgG1 were compared with sera from different categories of rubella infection. Both methods were based on an antiglobulin enzyme-linked immunosorbent assay. In one method the absorbances were compared with and without diethylamine (DEA) in the serum diluent over a range of serum dilutions and the difference between the dilution curves measured (DEA-shift). In the other, the absorbances at a single serum dilution were compared with and without urea in the wash fluid used after the antigen/serum incubation (avidity index). Various concentrations of DEA were also assessed in the avidity-index method, as this method is simpler to perform. The DEA-shift method was shown to be more sensitive for diagnosing recent primary rubella or immunization by demonstrating specific IgG1 of low avidity. The avidity-index method, however, was more specific when sera from cases of reinfection or non specific rubella IgM reactivity were tested. 35 mM DEA was found to be the optimal concentration of DEA when DEA was substituted for urea in the avidity index method. PMID- 1864908 TI - High quality of DNA retrieved for Southern blot hybridization from microwave fixed, paraffin-embedded liver tissues. AB - To overcome the degradation problem encountered in DNA extracted from formalin fixed, paraffin-embedded tissue blocks, several methods of tissue fixation were examined in order to improve the quality of the DNA recovered for use in nucleic acid analysis. The fixation methods included formalin fixation alone, alcohol fixation alone, and microwave fixation with tissues immersed in phosphate buffered saline (PBS), alcohol, or formalin. Unfixed fresh frozen tissue served as the control. Using hepatitis B virus (HBV) DNA sequences and the type I human procollagen gene as markers and liver tissue as a target, microwave fixation, with formalin omitted, not only preserved the DNA very well, but also the labile viral antigen. Both high molecular weight-integrated and free-form HBV DNAs were well preserved, and suitable for polymerase chain reaction and Southern blot analysis. The restriction enzyme fragment pattern of DNA recovered from these paraffin blocks was identical to that of unfixed fresh frozen tissue. Microwave fixation also preserved the labile preS2 epitope of the hepatitis B surface antigen (HBsAg) considerably better than formalin. These results suggest that microwave fixation is superior to routine formalin fixation for the preservation of excellent quality of genomic and viral DNAs for nucleic acid hybridization analysis. Alcohol, often used for nucleic acid purification, was also a good fixative for preserving DNA and the antigenicity of the labile antigen, especially when carried out in combination with microwave fixation. PMID- 1864909 TI - A serogroup specific enzyme-linked immunosorbent assay for the detection and identification of African horse sickness viruses. AB - A serogroup specific, indirect, sandwich ELISA was developed for the rapid detection of African horse sickness virus and viral antigens in field samples or in infected tissue cultures. The assay was shown to be highly sensitive and capable of providing confirmation of clinical diagnosis within one day. The results demonstrated that this ELISA will be useful for epidemiological surveillance of insect and mammalian host populations. PMID- 1864910 TI - Detection of virus-associated dsRNA from leafroll infected grapevines. AB - A simple procedure is described for reproducible detection of double stranded (ds) RNAs in leafroll infected grapevines. The procedure involves the extraction of tissues by a medium which preferentially yields dsRNA. The RNA is purified by CF11 cellulose chromatography and gel electrophoresis. The dsRNAs varied in size in different vines. In the cases tested they did not cross hybridize and occurred at higher concentrations in stem cortex tissues than in leaves. They were not detectable in healthy vines, could be passaged with the disease to healthy plants by graft inoculation and removed by virus elimination procedures. These observations indicated that the dsRNAs are of viral origin and that a number of viruses are associated with the grapevine leafroll disease. PMID- 1864911 TI - Estimating WAIS-R IQ from the National Adult Reading Test: a cross-validation. AB - The National Adult Reading Test (NART) was devised to predict premorbid intellectual functioning in people suspected of having dementia, so that the extent of cognitive decline could be assessed by comparing these results with current performances. This study undertook a double cross-validation of the NART on a neurologically normal sample (N = 104) and on a clinically relevant sample (49 aged subjects). The results provide encouragement for the clinical utility of the NART. The study also demonstrated that the inclusion of demographic variables with the NART gives a substantially better estimate of premorbid cognitive functioning than that given by the NART or by demographic data alone. PMID- 1864912 TI - Right-hemisphere language dominance in temporal lobe epilepsy: clinical and neuropsychological correlates. AB - Prior to and following temporal lobe surgery, patients with right-hemisphere language dominance and focal left temporal lobe epilepsy (RHLD-LTLSz) were compared to right-handed patients with left-hemisphere language dominance and either left temporal lobe epilepsy (LHLD-LTLSz) or right temporal lobe epilepsy (LHLD-RTLSz). The group of RHLD-LTLSz patients had a more consistent history of brain involvement before the age of 5 years and had a higher seizure frequency rating than did either LHLD patient group. Cognitively, RHLD-LTLSz patients did not show significant deficits in psychometric intellectural scores. In addition, they did not demonstrate comparable degrees of verbal memory loss as found either pre- or postoperatively in LHLD-LTLSz patients. The right-handed RHLD-LTLSz and the right-handed LHLD-LTLSz groups both appeared to exhibit bilaterally depressed fine-motor coordination. The left-handed RHLD-LTLSz patients did not show the same motor deficiencies. These latter findings suggest that hemispheric dominance for bilateral motor control may exist independent of language dominance, but not independent of handedness. PMID- 1864913 TI - A cognitive and behavioural phenotype in Williams syndrome. AB - Comparisons between children with Williams syndrome and control group children matched for age, sex, social class, and verbal intelligence provide support for a cognitive and behavioural phenotype in Williams syndrome. Children with the syndrome showed higher rates of behavioural and emotional difficulties when compared with the control group children, particularly in terms of concentration difficulties, excessive anxiety, and poor relationships with peers; and they also had significantly poorer visuo-spatial and motor skills. However, the Williams syndrome children were not uniformly poor in all areas of nonverbal abilities. Their visual recall skills were as good as those of the control group children, and their performance was superior to that of the control group children on a task of face recognition and on tasks requiring recall of verbal material. PMID- 1864914 TI - Cognitive and motor abilities in preschool hydrocephalics. AB - The neuropsychological performance of three groups of preschool children was evaluated: (a) one with hydrocephalus associated with myelomeningocele; (b) one with hydrocephalus associated with intraventricular hemorrhage and very low birth weight; and (c) a nonhydrocephalic normal comparison group. Multivariate profile analysis revealed lower levels of performance on measures of verbal and nonverbal cognitive skills for both groups of hydrocephalic children relative to normals. Comparison of group profiles on tasks requiring figure copying as opposed to figure matching and analysis of specific gross and fine motor skills revealed that both hydrocephalic groups had impaired visual-motor integration in the presence of average visual perceptual matching. In addition, different patterns of motor skill deficits were found for each hydrocephalic group. The results of this study suggest that decreased visual-motor integration and etiology-specific motor deficits are major sequelae of these forms of hydrocephalus in the preschool years. PMID- 1864915 TI - An empirical subgrouping of Finnish learning-disabled children. AB - The internal and external validity of a subgrouping of 82 Finnish children with relatively mild learning disabilities and 84 Controls was explored. The sample was selected from a total population of 1607 second grade pupils. Eight neuropsychological measures from four function areas were selected as classification criteria in cluster analysis. Six consistent and clinically meaningful subgroups were derived. These subgroups were designated as follows: (1) Normal, (2) General Language, (3) Visuo-Motor, (4) General Deficiency, (5) Naming, and (6) Mixed. Most of the LDs were clustered in subgroups (2) through (6); and most of the Controls, in subgroup (1). Several internal and external validation procedures indicated at least moderate validity in the subgroups, with the exception of the Mixed subgroup. The five valid subgroups encompassed 82% of the LDs and 90% of the Controls, and moreover, resembled subgroups which previously have been found among English-speaking children. This suggests that language differences exert no significant effect on the types of the emerging subgroups. PMID- 1864916 TI - Automatic temporal order judgment: the effect of intentionality of retrieval on closed-head-injured patients. AB - Closed-head-injured (CHI) and control groups were tested on a temporal order task under intentional and incidental retrieval conditions. Subjects were given five presentations of a list of nouns. In the incidental retrieval condition, subjects were told that they were to remember the words but that the order was not important. In the intentional retrieval condition, subjects were given the words in an order different from that in which they were originally presented and were asked to reorder the words to match the original order. For both conditions we compared the order in which words were recalled to the order in which they were originally presented. The results suggest that temporal order memory had more effortful characteristics in the intentional than in the incidental retrieval condition. The two groups did not differ significantly in the incidental retrieval condition. However, while the control group showed a significant improvement in the intentional retrieval condition. CHI groups performance did not significantly change. This study highlights two major points: (1) intentionality at the retrieval stage determines the effortfulness with which information is processed; (2) the more automatic the tasks, the better it is preserved following closed-head injury. PMID- 1864917 TI - Mirror phenomena in language and nonverbal activities--a case report. AB - A case is described of a 38-year-old, left-handed female who demonstrated mirror phenomena for both language and non-motor, nonverbal material. She mirror-wrote with her left hand with normal right-hand writing. Mirror-reading as well as object and spatial reversals were revealed. These data are consistent with bilateral representation of visual engrams, with one hemisphere containing a mirror-reversed representation of the other. PMID- 1864918 TI - Establishing the reliability and validity of neuropsychological disorders with low base rates: some recommended guidelines. AB - The issues of low prevalence in the context of the diagnosis of neuropsychological disorders in the larger community is discussed. Guidelines are proposed for producing reliability and validity estimates which are clinically, as well as statistically meaningful. PMID- 1864919 TI - Implicit and explicit memory in Alzheimer's disease and Parkinson's disease. AB - Several tasks examined implicit and explicit memory in demographically matched samples of Alzheimer's (AD) and Parkinson's disease (PD) patients, and healthy elderly subjects. A fragmented pictures test, word stem-completion repetition priming, and a pursuit-rotor tracking task, followed by explicit memory tests, were given. AD patients were impaired on all explicit tests and on word stem completion priming, but were intact on pursuit-rotor tracking and the skill learning (SL) component of the fragmented pictures test. PD patients were significantly better than AD patients on all explicit memory tests, but were selectively impaired on the SL component of the fragmented pictures test. Finally, a mirror-reading test was given to the PD patients and control subjects, with no significant differences found in performances between the two groups. Results are discussed in terms of hypothetical cognitive processes and brain circuits underlying different implicit and explicit memory domains. PMID- 1864920 TI - Memory deficits in Wilson's disease: a response to Lang. AB - Lang (1989) suggested that patients with Wilson's disease do not have memory deficits, unless they suffer from severe neurologic impairment. Results from three recent studies conflict with this view. The interaction of neurologic and cognitive deficits in Wilson's disease is discussed. PMID- 1864921 TI - A critical note on Lezak's 'best performance method' in clinical neuropsychology. AB - A fundamental problem in clinical neuropsychology is the estimation of premorbid levels of cognitive functioning. Lezak (1983) described the so-called 'best performance method' of estimating premorbid abilities. Essentially, this method consists in using the highest test scores or the best performance in everyday tasks as the best estimate of premorbid ability. This paper describes three studies of the empirical consequences of using the 'best performance method': The first study demonstrates that application of this method on WAIS subtests leads to a gross overestimation of intelligence as measured by the IQ. The second study corroborates this finding and also shows that overestimation of intelligence leads to systematic errors in the expected performance in neuropsychological tests in normal subjects. Finally, the third study shows that this is also the case in patients with diffuse cerebral atrophy. PMID- 1864922 TI - The two-component hypothesis of memory deficit in Alzheimer's disease. AB - Becker (1988) has argued that Alzheimer's disease is particularly characterised by a combination of amnesic and dysexecutive deficits. He has supported this hypothesis by identifying patients who represent a relatively pure example of each of these. We describe a search for similarly pure patients in a sample of 55 carefully selected Alzheimer cases. We succeed in identifying one case each of relatively pure amnesia and relatively pure dysexecutive syndrome. We also, however, find cases of predominant STM deficit, as well as cases with defective visual but not verbal memory, and cases of the converse pattern. These cases do not seem to reflect simple random variation in the data, since less theoretically coherent patterns of symptoms are not found in this pure form. We conclude that AD can give rise to relatively specific cognitive deficits during its early stages, but that these do not necessarily argue for Becker's two-component interpretation of the cognitive deficit in Alzheimer's disease. PMID- 1864923 TI - Comparison study of broth macrodilution and microdilution antifungal susceptibility tests. AB - An evaluation of broth dilution antifungal susceptibility tests was performed by determining both the micro- and macrodilution MICs of amphotericin B, flucytosine, fluconazole, ketoconazole, and cilofungin against 38 isolates of Candida albicans, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans, and Torulopsis glabrata. The following preliminary antifungal working group recommendations of the National Committee for Clinical Laboratory Standards for broth macrodilution tests with antifungal agents were used: inocula standardized to 1 x 10(4) to 5 x 10(4) CFU/ml with a spectrophotometer, RPMI 1640 medium buffered with morpholinopropanesulfonic acid (pH 7.0), incubation at 35 degrees C for 24 to 48 h, and an additive drug dilution procedure. Broth microdilution MICs were higher (two or more dilutions) than broth macrodilution MICs for all isolates tested with amphotericin B and for most isolates tested with ketoconazole, fluconazole, and cilofungin. MICs of flucytosine were the same by both techniques or lower by the broth microdilution test except in tests with C. neoformans. However, the only statistically significant differences between the two tests were observed with amphotericin B against all isolates (P = 0.01 to 0.07), ketoconazole against C. neoformans (P = 0.01 to 0.02), and cilofungin against C. albicans (P = 0.05 to 0.14). Tests performed with less dense inocula (1 x 10(3) to 5 x 10(3] produced similar results. PMID- 1864924 TI - New aniline blue dye medium for rapid identification and isolation of Candida albicans. AB - Organic dyes have long been used in diagnostic microbiology to differentiate species by color reactions. We studied the ability of a new noninhibitory medium, YM agar containing 0.01% aniline blue WS dye, Colour Index 42780 (YMAB), to identify Candida albicans among 1,554 yeast specimens obtained from seven clinical laboratories. Appropriate American Type Culture Collection and other characterized strains served as controls. A total of 487 of the clinical strains were identified as C. albicans. The remainder were other Candida species and non Candida yeasts. Clinical isolates and controls were grown on Sabouraud agar for 18 h at 30 degrees C and then transferred to YMAB. Plates were incubated for 12 to 18 h at 30 degrees C, and colonies were observed for yellow-green fluorescence under long-wave UV light (A365). All control strains of C. albicans and Candida stellatoidea fluoresced, as did 480 of the 490 isolates designated as C. albicans (which included 3 strains of C. stellatoidea). Cells of C. albicans grown on YMAB produced germ tubes in serum. Only five of the other 1,062 non-C. albicans yeasts fluoresced. The sensitivity and specificity were 98.0 and 99.5%, respectively, with a predictive value of 99.1%. A fluorescent metabolite was found in cell wall particulate fractions of C. albicans sonic extracts grown on YMAB but not in non C. albicans yeasts. This metabolite showed the same spectral curve as those of metabolites from whole cells in a recording spectrofluorometer when it was excited at 400 nm and scanned from 420 to 550 nm. Thus, growth on YMAB generates the production of a fluorescent moiety that can be used to specifically identify C. albicans within 12 to 18 h. PMID- 1864925 TI - DNA fingerprinting of isolates of Staphylococcus aureus from newborns and their contacts. AB - During a study on the epidemiology of Staphylococcus aureus colonization in newborns, mothers, and hospital staff, S. aureus was isolated from 536 of 1,945 specimens. Ninety-three isolates of S. aureus from the three groups of individuals were included in a study to evaluate the potential of DNA fingerprinting for strain differentiation. The 93 isolates were also phage typed and their plasmid profiles were analyzed. Cleavage of DNA with BamHI resulted in 13 different DNA restriction endonuclease band patterns (DNA REBPs), one of which consisted of eight isolates whose DNA was not cleaved with BamHI. The DNAs from these eight isolates were easily cleaved with HindIII. The different DNA REBPs were stable both during in vitro and in vivo growth and allowed strain differentiation within phage groups or types. We could not show any strong association between DNA REBP classes, phage types or groups, and plasmid profiles. Of the 93 isolates, 27 (29.0%) could not be phage typed and 12 (12.9%) lacked plasmids. We therefore conclude that DNA fingerprinting is a powerful tool, in addition to phage typing and plasmid profile analysis, for strain differentiation of S. aureus. PMID- 1864926 TI - Isolation and characterization of Sporothrix schenckii from clinical and environmental sources associated with the largest U.S. epidemic of sporotrichosis. AB - The largest recorded epidemic of sporotrichosis in the United States occurred in 1988 and involved a total of 84 cases in 15 states. All cases were associated with Wisconsin-grown sphagnum moss. Twenty-one clinical isolates of Sporothrix schenckii and 69 environmental isolates of Sporothrix spp. from the epidemic were characterized and compared. The environmental isolates were recovered from 102 samples of sphagnum moss and other material by using direct plating techniques. Characteristics examined included macroscopic and microscopic morphology, conversion to a yeast phase, exoantigen reactions, and virulence in mice. On the basis of these studies, eight environmental isolates were identified as S. schenckii, five were identified as Ophiostoma stenoceras, and the remainder were identified as Sporothrix species. The environmental isolates of S. schenckii were recovered from moss samples from one Pennsylvania nursery and from three New York State Soil and Water Conservation districts, but none were recovered from moss directly from the bogs in Wisconsin. PMID- 1864927 TI - Identification of Clostridium botulinum, Clostridium argentinense, and related organisms by cellular fatty acid analysis. AB - On the basis of 686 analyses of 285 strains of Clostridium botulinum, Clostridium argentinense (formerly C. botulinum type G), and phenotypically related organisms, 14 cellular fatty acid (CFA) groups of toxic organisms and 6 CFA groups of nontoxic organisms were delineated. The CFA groups of toxic strains included two of type A, three of proteolytic strains of type B, two of proteolytic strains of type F, one each of nonproteolytic strains of types B, E, and F, and one each of types C alpha, C beta, and D and C. argentinense. The groups of phenotypically similar nontoxic strains included Clostridium sporogenes, Clostridium putrificum, nontoxic strains with phenotypic characteristics similar to those of nonproteolytic strains of C. botulinum types B, E, and F (BEF-like), two groups of nontoxigenic organisms with phenotypic characteristics similar to those of C. botulinum types C and D and Clostridium novyi (CDN-like), and Clostridium subterminale, which has phenotypic characteristics similar to those of C. argentinense. Within the toxin types, 89 to 100% of the strains were correctly identified by CFA analysis, and 74 to 100% of the analyses were correct. Of 36 strains of C. sporogenes, 30 (83%) were correctly identified; 17% of the strains of C. sporogenes were incorrectly identified as C. botulinum type A or B. All analyses of C. putrificum and C. subterminale were correctly identified. There was no significant level of similarity between strains of C. botulinum and phenotypically similar organisms and 85 other species of clostridia or 407 other taxa of gram-positive and gram negative bacteria. Additionally, the one strain each of Clostridium baratii and Clostridium butyricum previously reported to produce C. botulinum toxin could be differentiated from C.botulinum types as well as from strains of C. baratii and C. butyricum that did not produce neurotoxin. PMID- 1864928 TI - Evaluation of a recombinant human T-cell lymphotropic virus type I (HTLV-I) p21E antibody detection enzyme immunoassay as a supplementary test in HTLV-I/II antibody testing algorithms. AB - To evaluate the usefulness of a human T-cell lymphotropic virus type I (HTLV-I) recombinant p21E immunoassay as a supplementary test in HTLV-I/II serologic testing algorithms, we used this assay to test 378 serum samples previously categorized as positive, indeterminant, or negative for HTLV-I/II antibody, as defined by U.S. Public Health Service guidelines. We found this test to be highly sensitive for detecting antibody to HTLV-I/II env (99.4%) but slightly less specific (96.0%), particularly among samples from intravenous drug users. Our data suggest that this test is most appropriately used to confirm the absence of env antibody in samples which are repeatably reactive in an HTLV-I/II screening assay and gag reactive only by immunoblotting. Because of the high sensitivity of this recombinant p21E test, a negative result in this context could preclude radioimmunoprecipitation testing. However, pending further evaluation of the specificity of this assay, samples testing positive for p21 env antibody may require confirmation by radioimmunoprecipitation, particularly in situations in which the results will be used for diagnostic purposes or blood donor counseling. PMID- 1864929 TI - High prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic Hispanics. AB - In this study, we estimated the prevalence of Helicobacter pylori infection and histologic gastritis in 58 asymptomatic Hispanic adult volunteers (mean age, 41 years; 59% male) by endoscopic biopsy of the upper gastrointestinal tract. Forty six subjects (79%) were found to harbor H. pylori in gastric biopsies, and all had histologic gastritis. Four other subjects were found to have gastritis in the absence of H. pylori. Similar prevalences of H. pylori and gastritis were noted in all age groups and also in American-born and immigrant Hispanics. Biopsy data and serologic studies of H. pylori antibodies correlated well. We conclude that H. pylori infection is an almost universal finding in the gastric mucosa of asymptomatic adult Hispanics, regardless of age. The clinical significance of these findings is unknown, but we speculate that H. pylori and its associated gastritis could have a role in the high incidence of gastric carcinoma in Hispanic populations. PMID- 1864930 TI - Evaluation of a commercially available enzyme-linked immunosorbent assay for Giardia lamblia antigen in stool. AB - The lack of a quick, simple, and inexpensive diagnostic test has limited the ability of public health officials to rapidly assess and control outbreaks of Giardia lamblia in child day-care centers. We evaluated the performance of a commercially available enzyme-linked immunosorbent assay (ELISA) for the detection of a G. lamblia-associated antigen in stool. Stool specimens were collected from the diapers of 426 children attending 20 day-care centers, fixed in 10% Formalin and polyvinyl alcohol, and examined by microscopy by Formalin concentration and trichrome staining techniques. Specimens were also tested visually and spectrophotometrically by ELISA. Of 99 tests positive by microscopy, 93 were visually positive by ELISA (sensitivity, 93.9%). Of 534 tests negative for G. lamblia by microscopy, 32 (6.0%) were ELISA positive. However, on the basis of examination of multiple specimens from the same child, none of these could be considered false-positive ELISAs; the specificity of the ELISA was therefore 100%. The sensitivity of both microscopy and ELISA improved as the number of specimens per child increased. An optical density value of greater than 0.040 was 98.0% sensitive and 100% specific for G. lamblia. This ELISA, which appeared to be more sensitive for G. lamblia than did microscopic examination of stool, should be useful as an epidemiologic tool, particularly in day-care settings, and may also have a role in confirming clinical diagnoses of giardiasis. PMID- 1864931 TI - Preliminary evaluation of Biolog, a carbon source utilization method for bacterial identification. AB - The Biolog Identification System (Biolog, Inc., Hayward, Calif.) is a new bacterial identification method that establishes an identification based on the exchange of electrons generated during respiration, leading to a subsequent tetrazolium-based color change. This system tests the ability of a microorganism to oxidize a panel of 95 different carbon sources. We report on a preliminary investigation of the ability of the instrument to identify, using its computer driven enzyme immunoassay reader, a diverse group of clinically relevant members of the family Enterobacteriaceae and gram-negative non-Enterobacteriaceae. The Biolog reported identifications (correct or incorrect) for 266 of 352 organisms tested (75.6%). Of the 266 identifications reported, 87.3% were correct at the genus level and 75.6% were correct at the species level at 24 h. In the total study of 352 strains, 46.6% were correct to the species level at 4 h and 57.1% were correct to the species level at 24 h. The error rate was 10.4% after 4 h and 9.6% after 24 h. The Biolog performed well with many genera, but problems were encountered with some strains of Klebsiella, Enterobacter, and Serratia. We found the system to be versatile and easy to use. PMID- 1864932 TI - Use of immunofluorescence to identify measles virus infections. AB - Monoclonal antibody to measles virus was used successfully to identify measles virus antigen directly in clinical specimens, as well as in cell cultures. Pooled nasopharyngeal-throat swab specimens had a higher yield than throat swabs or urine samples for virus detection. Use of A549 cell cultures in the spin amplification vial assay proved to be highly efficient, allowing virus recognition within 1 to 2 days of inoculation. A combination of appropriately collected specimens, which includes a nasopharyngeal-throat swab, direct antigen detection with monoclonal antibody to measles in an indirect immunofluorescence system, and the spin amplification vial assay using A549 cells provides a sensitive and rapid system for isolation and/or identification of measles virus infections. PMID- 1864933 TI - High frequency of coinfecting enteropathogens in Aeromonas-associated diarrhea of hospitalized Peruvian infants. AB - Rectal swabs from 391 infants less than 18 months of age who were hospitalized with acute diarrhea and from 138 similarly aged healthy infants were examined for the etiologic agents of diarrhea. Aeromonas spp. were recovered from 205 of 391 (52.4%) diarrheic patients, whereas they were recovered from 12 of 138 (8.7%) controls (P less than 10(-11). Among the 205 Aeromonas-positive diarrheic patients, 118 (57.6%) were found to be coinfected with other common enteropathogens. Of the 164 Aeromonas-positive initial diarrheic specimens, 82 (50.0%) had one or more other enteropathogens present; 30 patients were coinfected with rotavirus, 20 with enterotoxigenic Escherichia coli, 16 with Campylobacter spp., 14 with Shigella spp., 13 with enteropathogenic E. coli, 4 with Vibrio spp., 1 with Salmonella spp., and 1 with Plesiomonas spp. of Aeromonas strains from cases compared with that from controls supports an etiologic role for this organism. However, frequent concomitant infections with other well-recognized enteropathogens and a lack of disease correlation with common Aeromonas phenotypes suggest that only a subset of Aeromonas strains may be diarrhea causing and that such strains may be common to several of the existing species. PMID- 1864934 TI - Characterization of Gardnerella vaginalis and G. vaginalis-like organisms from the reproductive tract of the mare. AB - Gardnerella vaginalis has been isolated from women with bacterial vaginosis, from the genital tracts of asymptomatic women, and from several other infected body sites in humans. However, until recently, it has not been isolated from any other animal species. Between June 1988 and October 1989, 31 isolates identified as G. vaginalis and 70 isolates identified as G. vaginalis-like organisms have been recovered from the genital tracts of 93 mares from Michigan and Ohio. Identification was based on biochemical reactions, hemolysis on media containing blood from various animal sources, and susceptibility to select antimicrobial agents. This report details the characterization of G. vaginalis and G. vaginalis like organism isolates obtained from the reproductive tracts of these mares and compares the equine isolates with human isolates. PMID- 1864935 TI - Immune capture and detection of Borrelia burgdorferi antigens in urine, blood, or tissues from infected ticks, mice, dogs, and humans. AB - Current biological and serological techniques for demonstrating infections by Borrelia burgdorferi can be inconclusive. In order to monitor Lyme borreliosis, we developed a rapid and sensitive assay for B. burgdorferi antigens in infected hosts. Polyclonal rabbit antisera were raised against membrane vesicles and an 83 kDa vesicle-associated protein band that was purified from in vitro B. burgdorferi cultures. Immunoglobulin G (IgG) antibodies were recovered from these sera and tested for a species-specific reaction with several geographically diverse Borrelia isolates by immunoblot analysis. Parlodion-coated electron microscope grids were activated with anti-vesicle F(ab')2 fragments and then incubated with confirmed or experimental sources of spirochetal antigens. Such sources included cultured spirochetes; spirochete culture supernatants; samples of urine, blood, or serum from mice, dogs, and humans; triturates of Ixodes ticks; and bladder, spleen, liver, kidney, heart, or brain tissues from infected or control mice. Captured antigens were assayed by immune electron microscopy by using anti-83-kDa IgG antibodies and protein A-colloidal gold conjugates. The results indicated that B. burgdorferi appears to shed surface antigens which are readily detectable in urine, blood, and several organs from infected hosts. Such antigens were detectable in mouse urine at dilutions exceeding 10(-6). Intact spirochetes were frequently observed on grids incubated with blood, spleen, or bladder preparations, and B. burgdorferi was reisolated from the urinary bladders of all experimentally infected mice. These results indicated that B. burgdorferi antigens arise in a variety of host materials. Such antigens can be captured and identified with specific polyclonal antibodies, providing a sensitive assay for monitoring and studying Lyme borreliosis. PMID- 1864936 TI - Determination of genetic variation within Plasmodium falciparum by using enzymatically amplified DNA from filter paper disks impregnated with whole blood. AB - A new method which allows the enzymatic amplification of DNA extracted from whole blood dried on filter paper disks is presented. The method was used to study heterogeneity within an erythrocyte-binding antigen (EBA-175) of Plasmodium falciparum. Blood specimens from malaria-infected patients in Southeast Asia and Africa were spotted onto filter paper, dried, and transported for processing. P. falciparum DNA was extracted by boiling the filter paper disks in the presence of Chelex-100 ion-chelating resin, amplified by the polymerase chain reaction, and analyzed for the presence of genetic variation. In all cases examined, plasmodial DNA was successfully amplified and characterized from filter paper disks. Hybridization of the polymerase chain reaction products with internal probes demonstrated simultaneous infection with two strains of P. falciparum in two patients. This technique represents a sensitive and practical field method for the determination of genetic variation within P. falciparum and the study of molecular epidemiology. PMID- 1864937 TI - Construction of a DNA probe and detection of Actinobacillus pleuropneumoniae by using polymerase chain reaction. AB - A 1.5-kb Actinobacillus pleuropneumoniae 4074 DNA fragment from a genomic library was found to hybridization. No cross-hybridization hybridization. No cross hybridization was detected with DNAs from hemolytic members of the family Pasteurellaceae. From the nucleotide sequence of the putative genomic probe, three primers were synthesized for use in polymerase chain reactions (PCRs), with 31 strains tested by using purified and crude DNA targets. PCR amplification products of 610 and 985 bp were observed in nucleic acids extracted from the 12 known serotypes and a biotype 2 strain. Template DNAs from other gram-negative and gram-positive bacteria, some of them found in the normal flora of swine and the upper respiratory tract, were not amplified by PCR. The only exception was an amplification of a similar 610- or 985-bp sequence in Actinobacillus lignieresii, a species that is closely related to A. pleuropneumoniae but that has never been isolated from swine. Amplification of specific A. pleuropneumoniae sequences by PCR directly from clinical specimens may find applications in the identification of asymptomatic carriers as well as in efforts to eradicate porcine pleuropneumonia. PMID- 1864938 TI - Genetic diversity and identification of human infection by amplification of the chlamydial 60-kilodalton cysteine-rich outer membrane protein gene. AB - The 60-kDa cysteine-rich outer membrane protein genes of Chlamydia psittaci, Chlamydia pneumoniae, and Chlamydia trachomatis have very different 5' ends, but two areas flanking this variable region show absolute sequence conservation. This observation permitted differentiation of the three species of Chlamydia by the polymerase chain reaction (PCR), forming the basis of a diagnostic test for chlamydial infections. The PCR product containing the variable region of the respective 60-kDa CrP genes was also subjected to restriction endonuclease digestion, enabling differentiation of individual type strains of C. psittaci. Differentiation was possible between lymphogranuloma venereum and trachoma isolates of C. trachomatis. The PCR-based diagnostic test was successful with all strains of chlamydiae studied. The PCR primers showed high specificity and did not produce any product with common bacterial pathogens that may share the same sites of infection. PMID- 1864939 TI - Aeromonas trota sp. nov., an ampicillin-susceptible species isolated from clinical specimens. AB - Previous DNA hybridization studies established 12 Aeromonas genospecies, from which nine phenotypic species have been proposed: Aeromonas hydrophila, A. sobria, A. caviae, A. media, A. veronii, A. schubertii, A. salmonicida, A. eucrenophila, and A. jandaei. We have delineated a new Aeromonas genospecies, A. trota, on the basis of 13 strains isolated primarily from fecal specimens from southern and southeastern Asia. All strains were highly related to the proposed type strain, AH2 (ATCC 49657T): 51 to 100% (60 degrees C) and 49 to 99% (75 degrees C), with 0.2 to 2.2 divergence. AH2 was only 16 to 41% (60 degrees C) related to all other Aeromonas type strains and DNA group definition strains. The unique profile of A. trota includes negative reactions for esculin hydrolysis, arabinose fermentation, and the Voges-Proskauer test, positive reactions for cellobiose fermentation, lysine decarboxylation, and citrate utilization, and susceptibility to ampicillin, as determined by the broth microdilution MIC method and the Bauer-Kirby disk diffusion method (10 micrograms). Nine of the A. trota strains were from a single study of 165 geographically diverse aeromonads. This finding questions the efficacy of screening fecal specimens for Aeromonas spp. with ampicillin-containing media and suggests a previously unrecognized prevalence of this new species. PMID- 1864940 TI - Effect of delays in processing on the survival of Mycobacterium avium-M. intracellulare in the isolator blood culture system. AB - Concentrations of Mycobacterium avium-M. intracellulare ranging from 10(-1) to 10(3) CFU/ml were added to blood, placed in Isolator tubes, and held at room temperature for intervals ranging from 4 h to 56 days before being processed (centrifugation and culture on Middlebrook 7H10 agar). At all concentrations tested, M. avium-M. intracellulare was recovered after hold times ranging from 4 h to 7 days; the number of final CFU actually increased progressively for hold times of 8 h or more. Hold times of up to 7 days did not increase the time from processing to the first appearance of visible colonies. At an inoculum of 10(2) CFU/ml, M. avium-M. intracellulare was recovered from Isolator tubes processed 56 days after inoculation. Two Isolator blood cultures were drawn from a patient with AIDS; M. avium-M. intracellulare was recovered from the sample processed immediately and from the sample processed after a hold time of 7 days. Since M. avium-M. intracellulare survives for prolonged periods in Isolator tubes, blood cultures may be collected in outpatient settings or in hospitals without mycobacterial culture facilities and shipped to reference laboratories for processing without loss of viability. PMID- 1864941 TI - Characterization of Staphylococcus hyicus with the ATB 32 Staph system and with conventional tests. AB - The ATB 32 Staph system correctly identified 45 of 54 Staphylococcus hyicus cultures isolated from pigs and cattle. The biochemical profiles of the remaining nine cultures were not listed in the product data base. The 40 porcine and 14 bovine cultures resulted in three and seven different biochemical profiles, respectively. In parallel experiments, almost all S. hyicus cultures showed hemolytic reactions on chocolate agar, had CAMP-like reactivities in the zone of lysis of the staphylococcal beta-lysin, and had bacteriolytic properties on Micrococcus luteus cells. In addition, the S. hyicus cultures were unpigmented, were DNase positive, expressed an S. hyicus-specific teichoic acid, and were usually coagulase positive in porcine plasma. Most of the porcine strains were protein A positive, and two porcine cultures were clumping factor positive. PMID- 1864942 TI - Detection of antigens and antibodies in the urine of humans with Plasmodium falciparum malaria. AB - Humans infected with Plasmodium falciparum frequently have elevated levels of proteins in their urine, but it is unclear if any of these proteins are parasite antigens or antimalarial antibodies. To resolve this question, urine samples from malaria patients and controls living in Thailand and Ghana were evaluated. Urine samples from 85% of the patients had elevated protein levels and contained proteins with Mrs ranging from less than 29,000 to greater than 224,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antisera were produced against urine from infected and control subjects. Antisera raised against infected, but not control, urine were positive by indirect immunofluorescence on P. falciparum parasites and immunoprecipitated approximately 12 unique bands from extracts of parasites metabolically labeled with 35S-methionine. These data suggest that a variety of P. falciparum antigens are released into urine during acute infection. It is also likely that anti-P. falciparum antibodies are present in the urine of malaria patients because samples from these patients, but not controls, were positive in indirect immunofluorescence assays and immunoprecipitated at least 19 P. falciparum antigens from extracts of metabolically labeled parasites. The detection of malarial antigens and antibodies in urine may lead to a new approach for the diagnosis of malaria. PMID- 1864943 TI - Class-specific immune response to Yersinia enterocolitica serotype O9 antigens as determined by enzyme-linked immunosorbent assay. AB - An enzyme-linked immunosorbent assay (ELISA) using lipopolysaccharide (S-LPS) as the antigen was used to analyze the antibody response in rabbits orogastrically and intravenously infected with virulent (plasmid-bearing) Yersinia enterocolitica O9 strains (pYV+) and with the avirulent (plasmid-cured) derivatives (pYV-). A significative response of immunoglobulin G (IgG), IgA, and IgM antibodies against the S-LPS antigen was evident in sera from the rabbits orogastrically infected with pYV+ strains. This immune response was stronger and persisted longer than those obtained with the corresponding pYV- strains. In contrast, few differences were observed in the titers and evolution of IgG, IgA, and IgM antibodies against the S-LPS antigen in rabbits intravenously infected with pYV+ and pYV- strains. These results suggest that the necessity of the virulence plasmid for the establishment of infection by Y. enterocolitica serotype O9 is conditioned by the infection route used. When the S-LPS ELISA was compared with the radial immunodiffusion test using the native hapten as the antigen, the results showed that the ELISA technique was more sensitive. However, only those sera obtained between 2 and 8 weeks postinfection from rabbits intravenously infected with plasmid-bearing strains were positive in the radial immunodiffusion test. PMID- 1864944 TI - Antimicrobial susceptibility testing of veterinary clinical isolates with the Sceptor System. AB - The Sceptor System (Becton Dickinson) was compared with an agar dilution method for antimicrobial susceptibility testing of veterinary clinical isolates. The results indicate that the Sceptor System may be used to test gram-positive and fastidious gram-negative bacteria. PMID- 1864945 TI - Synthetic oligonucleotide probes differentiate respiratory syncytial virus subgroups in a nucleic acid hybridization assay. AB - A new approach to respiratory syncytial virus subgroup differentiation has been developed on the basis of the hybridization of subgroup-specific synthetic oligonucleotides with viral mRNA. Two oligonucleotide probes were designed from the nucleotide sequences of an A and a B subgroup respiratory syncytial virus glycoprotein G gene. All 28 virus isolates tested were correctly classified by subgroup with these probes. PMID- 1864946 TI - False-positive reactions in the latex agglutination test for Cryptococcus neoformans antigen. AB - The latex agglutination test for Cryptococcus neoformans antigen is a simple and rapid procedure for the diagnosis of cryptococcal meningitis. Although the test is sensitive, care must be taken to prevent contamination of the sample, which may result in false-positive reactions. It was discovered in our laboratory that immersion of a platinum wire inoculating loop into a sample of cerebrospinal fluid prior to testing introduced interfering substances leading to nonspecific agglutination. After further studies, it was determined that trace amounts of surface condensation (syneresis fluid) from agar, either added to the cerebrospinal fluid or adhering to the loop, were the probable source of contamination. It is suggested that the latex agglutination test for C. neoformans antigen be performed prior to culture or on a separate sample. PMID- 1864947 TI - Incidence of toxigenic Campylobacter strains in South Africa. AB - Campylobacter strains can produce a heat-labile cytotonic toxin (CTON) and various cytotoxins (CTOX). Of 22 South African Campylobacter strains tested, 86% were toxigenic (77% produced CTON, 41% produced CTOX, and 32% produced both types) and 14% were toxin negative. Campylobacter jejuni strains were 67% CTON positive and 47% CTOX positive, whereas Campylobacter coli strains were 100 and 29% positive, respectively. PMID- 1864948 TI - Acute mesenteric lymphadenitis due to Yersinia pseudotuberculosis lacking a virulence plasmid. AB - A serotype 4a strain of Yersinia pseudotuberculosis lacking the virulence plasmid pYV (pYV- strain) was isolated from the mesenteric lymph nodes but not from the stool or the appendix of a 10-year-old girl with a diagnosis of acute mesenteric lymphadenitis. Microscopically, reticulocytic abscess and lymphadenitis were persent in the enlarged mesenteric lymph nodes. Antibody against the isolate was detected in the serum. The isolate was negative for the presence of plasmid pYV and plasmid pYV-mediated properties, including autoagglutination and calcium dependency, but was positive for chromosome-mediated properties, including invasion into HeLa cells and tissues of mice and the Sereny test. Mice were orally infected with this pYV- strain, and rapid elimination from the intestine occurred 14 days later. Hence, the potential to inhibit the phagocytosis encoded by plasmid pYV was lacking. As the pYV- strain was recovered from the mesenteric lymph nodes and the spleen, the invasiveness was encoded by chromosomal genes. The count of the pYV- strain in the mesenteric lymph nodes increased to 10(4.6) cells per g within 4 days. These findings suggest that pYV- Y. pseudotuberculosis was the causative agent of acute mesenteric lymphadenitis in the absence of gastroenteritis. PMID- 1864949 TI - Quantitation of group A beta-hemolytic streptococci in throat culture. PMID- 1864950 TI - Mechanisms of acute ischemic contractile failure of the heart. Role of intracellular calcium. PMID- 1864951 TI - Effects of growth hormone and insulin-like growth factor I on rabbit proximal convoluted tubule transport. AB - This in vitro microperfusion study examined the effects of growth hormone and insulin-like growth factor I (IGF-I) on proximal convoluted tubule (PCT) transport. Tubules were perfused with an ultrafiltrate-like solution and bathed in a serum-like albumin solution. Neither a physiologic (5 x 10(-10) M), nor a pharmacologic (5 x 10(-8) M) dose of growth hormone had an effect on PCT phosphate or bicarbonate transport, or volume absorption. Addition of 5 x 10(-9) M and 5 x 10(-8) M IGF-I, but not 5 x 10(-10) M IGF-I, to the bathing solution resulted in an increase (12-15%) in phosphate transport, but no change in volume absorption or bicarbonate transport. Addition of IGF-I to the luminal perfusate also stimulated phosphate transport. The effect was noted at a concentration of 5 x 10(-11) M IGF-I (27% stimulation) and was maximal at a concentration of 5 x 10( 10) M IGF-I (46% stimulation). There was no effect of luminal IGF-I on volume absorption or bicarbonate transport. These data indicate that growth hormone has no direct effect on PCT transport. In the PCT, IGF-I stimulates phosphate transport specifically and acts via both basolateral and apical membranes. However, the magnitude of the maximal response to the luminal addition of IGF-I was threefold greater than that measured upon addition of the hormone to the bath, and the stimulation occurred at a 100-fold lower concentration. These data are consistent with IGF-I mediating the in vivo stimulation of phosphate transport by growth hormone. PMID- 1864952 TI - Interleukin 2 mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells. AB - Previous reports have suggested the production of complement components C4, C2, and factor B by renal tissue. However, the cells involved in production of complement have not been identified. In this study metabolic labeling experiments demonstrated that human proximal tubular epithelial cells (PTEC) synthesize a 180 kD precursor of C3 that is secreted after proteolytic cleavage into a disulphide linked two-chain molecule as found in plasma. C3 present in culture supernatants of PTEC was functionally active, however, during the culture period there was a partial inactivation of the C3 molecule as assessed by hemolytic titration. Recombinant IL-2 enhances the rate of C3 synthesis in a dose-dependent manner reaching maximal stimulation at doses of 200-400 U/ml IL-2. Northern blot analysis demonstrated a 5.2-kb C3 mRNA species present in PTEC that was increased within 24 h of IL-2 treatment. IL-2-induced enhancement of C3 production by PTEC could be neutralized with specific antibodies to IL-2. This study demonstrates that C3 synthesis in PTEC is upregulated by IL-2, the major cytokine produced by activated T cells. PMID- 1864953 TI - Role of nitric oxide in renal medullary oxygenation. Studies in isolated and intact rat kidneys. AB - We investigated the role of the endothelial-derived relaxing factor nitric oxide (NO) in the homeostasis of O2 supply to the renal medulla, a region normally operating on the verge of hypoxia. Sensitive Clark-type O2 microelectrodes were inserted into renal cortex and medulla of anesthetized rats. The inhibitor of NO formation, L-NG-monomethylarginine (LNMMA), while increasing blood pressure and reducing renal blood flow, decreased medullary pO2 from 23 +/- 3 mmHg to 12 +/- 3 (P less than 0.001), with no change in the cortex. These responses were promptly reversed by L-arginine, which bypasses the LNMMA blockade. In isolated rat kidneys, LNMMA reduced perfusion flow without altering glomerular filtration rate, and augmented deep medullary hypoxic injury to thick ascending limbs from 68 to 90% of the tubules (P less than 0.02). These changes were prevented by L arginine. Nitroprusside had a protective effect upon thick limb injury. Finally, in a previously reported model of radiocontrast nephropathy (1988. J. Clin. Invest. 82:401), LNMMA increased the severity of renal failure (final plasma creatinine from 2.3 +/- 2 mg% to 3.4 +/- 3, P less than 0.005) and the proportion of damaged thick limbs (from 24 +/- 6% to 53 +/- 9, P less than 0.01). Nitrovasodilatation may participate in the balance of renal medullary oxygenation and play an important role in the prevention of medullary hypoxic injury. PMID- 1864954 TI - Intestinal absorption of magnesium from food and supplements. AB - The purpose of this study was to measure magnesium absorption over the wide range of intakes to which the intestine may be exposed from food and/or magnesium containing medications. Net magnesium absorption was measured in normal subjects after they ingested a standard meal supplemented with 0, 10, 20, 40, and 80 mEq of magnesium acetate. Although absorption increased with each increment in intake, fractional magnesium absorption fell progressively (from 65% at the lowest to 11% at the highest intake) so that absorption as a function of intake was curvilinear. This absorption-intake relationship was almost perfectly represented by an equation containing a hyperbolic function plus a linear function. Our results are statistically compatible with a magnesium absorption process that simultaneously uses a mechanism that reaches an absorptive maximum, plus a mechanism that endlessly absorbs a defined fraction (7%) of ingested magnesium. Compared to previous studies of calcium absorption, much less magnesium that calcium was absorbed at intakes above 8 mEq/meal, apparently due to greater restriction of intestinal permeability to magnesium. We also found that magnesium from a high magnesium-containing food source, almonds, was just as bioavailable as from soluble magnesium acetate. In contrast, magnesium absorption from commercially available enteric-coated magnesium chloride was much less than from magnesium acetate, suggesting that enteric coating can impair magnesium bioavailability. PMID- 1864955 TI - Differential effects of microenvironmentally presented interleukin 3 versus soluble growth factor on primitive human hematopoietic cells. AB - The effect of IL-3 on hematopoiesis in long-term culture (LTC) was studied by cocultivating normal human marrow cells with human marrow fibroblast feeders engineered to constitutively produce IL-3 and by adding soluble IL-3 to LTC according to a variety of dose-time schedules. Feeders stably producing 7 ng/ml IL-3, or LTC to which 10 ng/ml IL-3 was added daily for 5 wk, but not once or twice weekly for the same time period, increased the output of mature nonadherent cells and progenitors from LTC as compared to control cultures. At the time of the weekly half-medium change, when primitive clonogenic progenitors in the adherent layer of standard LTC are quiescent, such cells were actively cycling in cultures containing a continuous source of an adequate dose of IL-3. In LTC, where the proportion of IL-3-producing cells in the feeder layer was diluted to 10% and no IL-3 was detectable in culture medium, primitive adherent layer progenitors were, nevertheless, maintained as a population of continuously proliferating cells. Thus, the presence of IL-3 in LTC can enhance the proliferation and differentiation of very early human hematopoietic cells, but the concentration, duration of exposure, and method of IL-3 presentation are important determinants of the ultimate effects observed. PMID- 1864956 TI - Transcellular water flow modulates water channel exocytosis and endocytosis in kidney collecting tubule. AB - The regulation of osmotic water permeability (Pf) by vasopressin (VP) in kidney collecting tubule involves the exocytic-endocytic trafficking of vesicles containing water channels between an intracellular compartment and apical plasma membrane. To examine effects of transcellular water flow on vesicle movement, Pf was measured with 1-s time resolution in the isolated perfused rabbit cortical collecting tubule in response to addition and removal of VP (250 microU/ml) in the presence of bath greater than lumen (B greater than L), lumen greater than bath (L greater than B), and lumen = bath (L = B) osmolalities. With VP addition, Pf increased from 12 to 240-270 x 10(-4) cm/s (37 degrees C) in 10 min. At 1 min, Pf was approximately 70 x 10(-4) cm/s for B greater than L, L greater than B, and L = B conditions. At later times, Pf increased fastest for L greater than B and slowest for B greater than L osmolalities; at 5 min, Pf was 250 x 10(-4) cm/s (L greater than B) and 158 x 10(-4) cm/s (B greater than L). With VP removal, Pf returned to pre-VP levels at the fastest rate for B greater than L and the slowest rate for L greater than B osmolalities; at 30 min, Pf was 65 x 10(-4) cm/s (B greater than L) and 183 x 10(-4) cm/s (L greater than B). For a series of osmotic gradients of different magnitudes and directions, the rates of Pf increase and decrease were dependent upon the magnitude of transcellular volume flow; control studies showed that paracellular water flux, asymmetric transcellular water pathways, or changes in cell volume could not account for the data. VP-dependent endocytosis was measured by apical uptake of rhodamine dextran; in paired studies where the same tubule was used for + and - gradients, B greater than L and L greater than B osmolalities gave 168% and 82% of uptake measured with no gradient. In contrast, endocytosis in proximal tubule was not dependent on gradient direction. These data provide evidence that transcellular volume flow modulates the vasopressin-dependent cycling of vesicles containing water channels, suggesting a novel driving mechanism to aid or oppose the targeted, hormonally directed movement of subcellular membranes. PMID- 1864957 TI - Three-dimensional characterization of human ventricular myofiber architecture by ultrasonic backscatter. AB - Normal human left ventricular architecture comprises a highly aligned array of cardiac myofibers whose orientation depends on transmural location. This study was designed to determine whether measurement of integrated backscatter could be used detect the progressive transmural shift of myofiber alignment that occurs from epicardium to endocardium in human ventricular wall segments. Integrated backscatter was measured at 32 transmural levels in seven cylindrical biopsy specimens (1.4 cm diam) sampled from normal regions of six explanted fixed human hearts by insonification of samples at 180 independent angles in 2 degrees steps around their entire circumference with a 5-MHz broadband piezoelectric transducer. Histologic analysis was performed to determine fiber orientation. Integrated backscatter varied approximately as a sinusoidal function of the angle of insonification at each transmural level. Greater integrated backscatter was observed for insonification perpendicular as compared with parallel to fibers (difference = 14.5 +/- 0.6 dB). Ultrasonic analysis revealed a progressive transmural shift in fiber orientation of approximately 9.2 +/- 0.7 degrees/mm of tissue. Histologic analysis revealed a concordant shift in fiber orientation of 7.9 +/- 0.8 degrees/mm of tissue. Thus, human myocardium manifests anisotropy of ultrasonic scattering that may be useful for characterization of the intramural fiber alignment and overall three-dimensional organization of cardiac myofibers. PMID- 1864958 TI - Prostacyclin production and mediation of adenylate cyclase activity in the pulmonary artery. Alterations after prolonged hypoxia in the rat. AB - Prostacyclin is a critical mediator of structure and function in the pulmonary circulation, causing both the inhibition of vascular smooth muscle growth and vasodilation via the stimulation of adenylate cyclase. To examine the potential role of alterations in prostacyclin production or mechanism of action in chronic hypoxic pulmonary hypertension, we determined the effects of prolonged (7 d) in vivo hypoxia on in vitro prostacyclin synthesis and mediation of adenylate cyclase activity in rat main pulmonary arteries. In control arteries prostacyclin production exceeded that of prostaglandin (PG) E2 by 25-fold, with 42% originating from the endothelium. Studies utilizing indomethacin revealed that endogenous prostaglandins mediate at least 69% of basal adenylate cyclase activity. Prostacyclin-stimulated enzyme activity was enhanced by exogenous GTP, indicating that this is a receptor-mediated process involving G protein amplification. Comparable dose-related responses to prostacyclin and PGE2 suggest that these agents may activate a common receptor. After 7 d of in vivo hypoxia there was a 2.7-fold increase in in vitro prostacyclin production, with equivalent increases in synthesis in the endothelium and vascular smooth muscle. However, despite this increase there was no change in basal adenylate cyclase activity, and this was associated with attenuated sensitivity of the enzyme to prostacyclin stimulation. Concomitant diminution of the response to beta adrenergic stimulation, with previously-demonstrated beta receptor downregulation and unaltered postreceptor-mediated activity, suggests that the blunted response to prostacyclin is due to receptor downregulation. Parallel studies of the thoracic aorta indicated that these changes are specific to the pulmonary artery. It is postulated that attenuation of the response of adenylate cyclase to prostacyclin may contribute to the structural changes and hypertension observed in the pulmonary vasculature of the rat with chronic hypoxia. PMID- 1864959 TI - Human anti-phosphorylcholine antibodies share idiotopes and are self-binding. AB - We have previously shown that BALB/c antipneumococcal polysaccharide antibodies with phosphorylcholine (PC) specificity are self-binding, mediated by hypervariable sequence structure of the heavy chain. We extended the observation of self-binding anti-PC antibodies to naturally occurring human anti-PC antibodies. Anti-PC antibodies were purified from normal donor sera and shown to bind to monoclonal antiidiotypic anti-T15 antibodies originally raised against the murine T15 idiotype. These human antibodies are self-binding which is inhibitable by the PC hapten and the murine T15 (50-73)-derived Vh peptide. The anti-PC antibodies were further separated into id-positive and id-negative anti PC antibodies. Only the T15 id-positive preparation was self-binding. These findings demonstrate an evolutionary, conserved biological property between mouse and man associated with a naturally occurring antibacterial antibody. This conserved biological and structural property may have been selected in evolution because it is part of an important immune defense mechanism against bacterial and other environmental pathogens. PMID- 1864960 TI - Mast cell tryptase is a mitogen for cultured fibroblasts. AB - Mast cells appear to promote fibroblast proliferation, presumably through secretion of growth factors, although the molecular mechanisms underlying this mitogenic potential have not been explained fully by known mast cell-derived mediators. We report here that tryptase, a trypsin-like serine proteinase of mast cell secretory granules, is a potent mitogen for fibroblasts in vitro. Nanomolar concentrations of dog tryptase strongly stimulate thymidine incorporation in Chinese hamster lung and Rat-1 fibroblasts and increase cell density in both subconfluent and confluent cultures of these cell lines. Tryptase-induced cell proliferation appears proteinase-specific, as this response is not mimicked by pancreatic trypsin or mast cell chymase. In addition, low levels of tryptase markedly potentiate DNA synthesis stimulated by epidermal growth factor, basic fibroblast growth factor, or insulin. Inhibitors of catalytic activity decrease the mitogenic capacity of tryptase, suggesting, though not proving, the participation of the catalytic site in cell activation by tryptase. Differences in Ca++ mobilization and sensitivity to pertussis toxin suggest that tryptase and thrombin activate distinct signal transduction pathways in fibroblasts. These data implicate mast cell tryptase as a potent, previously unrecognized fibroblast growth factor, and may provide a molecular link between mast cell activation and fibrosis. PMID- 1864961 TI - Exogenous insulin augments in healthy volunteers the cardiovascular reactivity to noradrenaline but not to angiotensin II. AB - Hyperinsulinemia has been implicated in the pathogenesis of the blood pressure elevation in patients with noninsulin-dependent diabetes mellitus, obesity, but also essential hypertension. In these conditions an increased cardiovascular reactivity to noradrenaline (NA) and angiotensin II (AII) can be observed. Using the euglycemic clamp technique, we determined the cardiovascular reactivity to graded infusions of NA and AII in nine healthy males before (Bas), and 1 and 6 h after infusion of insulin (50 mU/kg per h) was started. On separate days control experiments were carried out to control for any circadian variation. Insulin led to a decrease of the amount of circulating NA necessary to increase the diastolic blood pressure (DBP) 20 mmHg (actual experiment [mean +/- SEM]: Bas, 23.1 +/- 5.0; 1 h, 14.8 +/- 3.0; and 6 h, 12.3 +/- 3.1; and control experiment: Bas, 20.7 +/- 5.0; 1 h, 18.6 +/- 3.5; and 6 h, 17.3 +/- 3.3 nmol/liter; Bas vs. 1 and 6 h: P less than 0.05). Although the amount of NA infused to raise DBP 20 mmHg showed a similar decline after 1 h of insulin infusion, no such change from baseline could be observed at 6 h. This appeared to be due to an increase in NA clearance with more prolonged insulin infusion. Insulin exerted no effect on the amount of AII infused to increase DBP 20 mmHg (actual experiment: Bas, 27.6 +/- 6.4; 1 h, 28.8 +/- 10.0; and 6 h, 21.2 +/- 5.3; and control experiment: Bas, 33.6 +/- 5.7; 1 h, 34.2 +/- 6.1; and 6 h, 23.4 +/- 4.7 ng/kg/min; NS). We did observe a circadian variation in AII reactivity. Whether the increase in cardiovascular responsiveness to NA after administration of insulin contributes to the elevation in blood pressure frequently observed in patients with insulin resistance remains to be proven. PMID- 1864962 TI - Mutations of P450c21 (steroid 21-hydroxylase) at Cys428, Val281, and Ser268 result in complete, partial, or no loss of enzymatic activity, respectively. AB - Steroid 21-hydroxylase deficiency is the major cause of congenital adrenal hyperplasia (CAH), a common genetic disease. To define the relationship between gene mutations and enzyme deficiency, we generated missense mutations of the 21 hydroxylase cDNA at three different sites and characterized the mutant proteins after expressing them in cultured mammalian and yeast cells. Among them, Ser268 and Val281 have been found to be mutated in CAH patients, whereas Cys428 has been implicated as the heme ligand. Our results show mutations at these sites result in complete, partial, or no loss of the enzymatic activity. All the Cys428 mutants had neither enzymatic activity nor P450 absorption, thus supporting the notion that Cys428 is the heme ligand. All the 268-mutants exhibited the same activity as normal 21-hydroxylase, demonstrating that the clinically observed Ser268----Thr change represents a polymorphism rather than the cause of the enzyme deficiency. The 281-mutants had normal Km but greatly reduced Vmax values that also paralleled the reduction in the heme content, in the order Val281 (normal, 100%) greater than Ile281 (50%) greater than Leu281 (20%) greater than Thr281 (10%). Our findings suggest that the methyl group at the beta-carbon of Val281 is required for heme incorporation and consequently enzymatic activity. PMID- 1864963 TI - Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset. AB - Differential solute clearances were used to characterize glomerular function in 20 Pima Indians with noninsulin-dependent diabetes mellitus (NIDDM) of less than 3 yr duration. 28 Pima Indians with normal glucose tolerance served as controls. In the diabetic group, the glomerular filtration rate (GFR, iothalamate clearance) exceeded the control value by 15% (140 +/- 6 vs. 122 +/- 5 ml/min, P less than 0.01). A corresponding 12% increase in renal plasma flow (RPF) was not statistically significant and did not account fully for the observed hyperfiltration, suggesting a concomitant elevation of the ultrafiltration pressure or coefficient. The median albumin excretion ratio in NIDDM exceeded control by almost twofold (10.1 vs. 5.8 mg/g creatinine), a trend which just failed to achieve statistical significance (P = 0.06). Fractional clearances of dextrans of broad size distribution were also elevated in diabetic subjects, significantly so for larger dextrans of between 48 and 60 A radius. A theoretical analysis of dextran transport through a heteroporous membrane revealed glomerular pores in NIDDM to be uniformly shifted towards pores of larger size than in controls. We conclude that an impairment of barrier size selectivity combined with high GFR elevates the filtered protein load in NIDDM of recent onset. We propose that enhanced transglomerular trafficking of protein may predispose to sclerosis of glomeruli in those Pima Indians with NIDDM who ultimately develop diabetic nephropathy. PMID- 1864964 TI - Phosphatidic acid as a second messenger in human polymorphonuclear leukocytes. Effects on activation of NADPH oxidase. AB - Receptor-mediated agonists, such as FMLP, induce an early, phospholipase D (PLD) mediated accumulation of phosphatidic acid (PA) which may play a role in the activation of NADPH oxidase in human PMN. We have determined the effect of changes in PA production on O2 consumption in intact PMN and the level of NADPH oxidase activity measured in a cell-free assay. Pretreatment of cells with various concentrations of propranolol enhanced (less than or equal to 200 microM) or inhibited (greater than 300 microM) PLD-induced production of PA (mass and radiolabel) in a manner that correlated with enhancement or inhibition of O2 consumption in PMN stimulated with 1 microM FMLP in the absence of cytochalasin B. The concentration-dependent effects of propranolol on FMLP-induced NADPH oxidase activation was confirmed by direct assay of the enzyme in subcellular fractions. In PA extracted from cells pretreated with 200 microM propranolol before stimulation with 1 microM FMLP, phospholipase A1 (PLA1)-digestion for 90 min, followed by quantitation of residual PA, showed that a minimum of 44% of PA in control (undigested) sample was diacyl-PA; alkylacyl-PA remained undigested by PLA1. Propranolol was also observed to have a concentration-dependent enhancement of mass of 1,2-DG formed in PMN stimulated with FMLP. DG levels reached a maximum at 300 microM propranolol and remained unchanged up to 500 microM propranolol. However, in contrast to PA levels, the level of DG produced did not correlate with NADPH oxidase activation. Exogenously added didecanoyl-PA activated NADPH oxidase in a concentration-dependent manner (1-300 microM) in a reconstitution assay using membrane and cytosolic fractions from unstimulated PMN. In addition, PA synergized with SDS for oxidase activation. Taken together, these results indicate that PA plays a second messenger role in the activation of NADPH oxidase in human PMN and that regulation of phospholipase D is a key step in the activation pathway. PMID- 1864965 TI - Lipolysis exposes unreactive endogenous apolipoprotein E-3 in human and rat plasma very low density lipoprotein. AB - Endogenous apolipoprotein E in VLDL is poorly expressed in receptor binding processes. Yet catabolism of VLDL-remnants by cellular receptors depends on functional apo E molecules. To better understand remnant catabolism phenomena, we determined the metabolism of VLDL and post-lipolysis VLDL by cultured cells. Partial lipolysis was achieved by incubation of VLDL with lipoprotein lipase in vitro (human) or recirculation (rat) in supradiaphragmatic animals. Lipolyzed VLDL exhibit metabolic activities 2-20-fold higher than control VLDL, that are saturable and dependent on the presence of LDL receptors. The ligand responsible for receptor interaction of lipolyzed VLDL (apo E or apo B-100) and its source (endogenous or transferred) was studied with monoclonal antibodies and with lipoproteins from E-3/3 and E-2/2 subjects. The data unequivocally proved that lipolysis causes exposure of unreactive endogenous apo E-3 at the VLDL surface, possibly by a change of conformation of the protein. Apo B-100 becomes biologically expressed only in lipolyzed VLDL-III. Lipolyzed VLDL, however, is less reactive to exogenous apo E-3 than control VLDL indicating that endogenous and exogenous apo E are oriented differently in VLDL. It is proposed that VLDL delivers triglycerides to tissues when apo E is unreactive but becomes a remnant after the protein becomes exposed and directs the particles from lipoprotein lipase sites to cellular receptors. PMID- 1864966 TI - Effect of physiologic hyperinsulinemia on glucose and lipid metabolism in cirrhosis. AB - Insulin secretion and insulin sensitivity were evaluated in eight clinically stable cirrhotic patients and in 12 controls. OGTT was normal in cirrhotics but plasma insulin response was increased approximately twofold compared with controls. Subjects received a three-step (0.1, 0.5, 1.0 mU/kg.min) euglycemic insulin clamp with indirect calorimetry, [6-3H]-glucose, and [1-14C]-palmitate. During the two highest insulin infusion steps glucose uptake was impaired (3.33 +/- 0.31 vs. 5.06 +/- 0.40 mg/kg.min, P less than 0.01, and 6.09 +/- 0.50 vs. 7.95 +/- 0.52 mg/kg.min, P less than 0.01). Stimulation of glucose oxidation by insulin was normal; in contrast, nonoxidative glucose disposal (i.e., glycogen synthesis) was markedly reduced. Fasting (r = -0.553, P less than 0.01) and glucose-stimulated (r = -0.592, P less than 0.01) plasma insulin concentration correlated inversely with the severity of insulin resistance. Basal hepatic glucose production was normal in cirrhotics and suppressed normally with insulin. In postabsorptive state, plasma FFA conc (933 +/- 42 vs. 711 +/- 44 mumol/liter, P less than 0.01) and FFA turnover (9.08 +/- 1.20 vs. 6.03 +/- 0.53 mumol/kg.min, P less than 0.01) were elevated in cirrhotics despite basal hyperinsulinemia; basal FFA oxidation was similar in cirrhotic and control subjects. With low-dose insulin infusion, plasma FFA oxidation and turnover failed to suppress normally in cirrhotics. During the two higher insulin infusion steps, all parameters of FFA metabolism suppressed normally. In summary, stable cirrhotic patients with normal glucose tolerance exhibit marked insulin resistance secondary to the impaired nonoxidative glucose disposal. Our results suggest that chronic hyperinsulinism may be responsible for the insulin resistance observed in cirrhosis. PMID- 1864967 TI - Expression of the early growth response 1 and 2 zinc finger genes during induction of monocytic differentiation. AB - Members of the early growth response (EGR) gene family are rapidly induced after mitogenic stimulation of diverse cell types. The present work has examined EGR gene expression during differentiation of myeloid leukemia cells along the monocytic lineage and in activated monocytes. Low levels of EGR-1 transcripts were detectable in untreated U-937 and HL-60 leukemia cells. In contrast, treatment of these cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) was associated with increases (within 1 h) in EGR-1 mRNA levels. The induction of monocytic differentiation by TPA and other agents was further associated with increases in EGR-2, but not EGR-3 or EGR-4, mRNA levels in these cells. Treatment of resting peripheral blood monocytes with the macrophage colony-stimulating factor (M-CSF) was also associated with rapid (within 15 min) increases in expression of the EGR-1 and EGR-2 genes. The results of nuclear run-on assays demonstrate that EGR-1 mRNA levels are increased in part by transcriptional activation of this gene in M-CSF-stimulated monocytes. The results also demonstrate that both EGR-1 and EGR-2 mRNA levels are regulated at the posttranscriptional level by a labile protein that destabilizes these transcripts. Finally, we demonstrate that dexamethasone, an inhibitor of monocytic differentiation, blocks the associated increases in EGR-1 and EGR-2 expression. Taken together, the results indicate that the EGR-1 and EGR-2 early response genes are involved in the induction of myeloid leukemia cell differentiation along the monocytic lineage and in the activation of human monocytes. PMID- 1864968 TI - Sources of carbon for hepatic glycogen synthesis in the conscious dog. AB - To identify the source(s) of carbon for the indirect pathway of hepatic glycogen synthesis, we studied nine 42-h fasted conscious dogs given a continuous intraduodenal infusion of glucose, labeled with [1-13C]glucose and [3-3H]glucose, at 8 mg.kg-1.min-1 for 240 min. Glycogen formation by the direct pathway was measured by 13C-NMR. Net hepatic balances of glucose, gluconeogenic amino acids, lactate, and glycerol were determined using the arteriovenous difference technique. During the steady-state period (the final hour of the infusion), 81% of the glucose infused was absorbed as glucose. Net gut output of lactate and alanine accounted for 5% and 3% of the glucose infused, respectively. The cumulative net hepatic uptakes were: glucose, 15.5 +/- 3.8 g; gluconeogenic amino acids, 32.2 +/- 2.2 mmol (2.9 +/- 0.2 g of glucose equivalents); and glycerol, 6.1 +/- 0.9 mmol (0.6 +/- 0.1 g of glucose equivalents). The liver produced a net of 29.2 +/- 9.6 mmol of lactate (2.6 +/- 0.8 g of glucose equivalents). Net hepatic glycogen synthesis totaled 9.3 +/- 2.5 g (1.8 +/- 0.4 g/100 g liver), with the direct pathway being responsible for 57 +/- 10%. Thus, net hepatic glucose uptake was sufficient to account for all glycogen formed by both the direct and indirect pathways. Total net hepatic uptake of gluconeogenic precursors (gluconeogenic amino acids, glycerol, and lactate) was able to account for only 20% of net glycogen synthesis by the indirect pathway. In a net sense, our data are consistent with an intrahepatic origin for most of the three-carbon precursors used for indirect glycogen synthesis. PMID- 1864969 TI - Differences in the expression of the cardiopulmonary alterations associated with anti-immunoglobulin E-induced or active anaphylaxis in mast cell-deficient and normal mice. Mast cells are not required for the cardiopulmonary changes associated with certain fatal anaphylactic responses. AB - We compared the changes in heart rate (HR), pulmonary dynamic compliance (Cdyn), and pulmonary conductance (GL) associated with three different models of anaphylaxis in genetically mast cell-deficient WBB6F1-W/Wv and congenic normal (+/+) mice. Intravenous infusion of a monoclonal rat anti-mouse IgE produced a marked tachycardia, diminutions in Cdyn and GL, and death in +/+ but not W/Wv mice, and +/+ mice sensitized to develop high circulating levels of IgE exhibited HR, Cdyn, and GL responses to rat anti-IgE challenge which were significantly less intense than those in nonimmunized +/+ mice. By contrast, virtually identical cardiopulmonary responses were observed in either +/+ or W/Wv mice challenged to elicit pure active anaphylactic responses or simultaneous active and anti-IgE-dependent anaphylaxis. These findings show that anaphylactic responses associated with significant tachycardia, reductions in Cdyn and GL, and death can occur in the virtual absence of tissue mast cells. This is true even though, in normal mice, such responses are associated with extensive degranulation of tissue mast cells. By contrast, certain models of anaphylaxis, such as that induced in nonsensitized mice by anti-mouse IgE, can not be elicited in the absence of mast cells. PMID- 1864970 TI - Effects of body fat distribution on regional lipolysis in obesity. AB - To determine the contribution of the major body fat depots to systemic free fatty acid (FFA) availability, palmitate ([1-14C]-palmitate) release was measured from leg (lower body) and non-leg (upper body) fat in eight upper body obese (UB Ob), six lower body obese (LB Ob), and six nonobese (Non Ob) age-matched premenopausal women in the overnight postabsorptive state. Splanchnic palmitate release was determined in 16 of these subjects. RESULTS: total palmitate release was greater in UB Ob (P less than 0.005) than LB Ob or Non Ob women (161 +/- 16 vs. 111 +/- 9 vs. 92 +/- 9 mumol/min, respectively). Despite increased leg fat mass in obese women, leg palmitate release was similar in each group. Therefore, leg fat palmitate release was greater in Non Ob women than LB Ob (P less than 0.01) or UB Ob (P = 0.06) women (3.7 +/- 0.3 vs. 2.4 +/- 0.2 vs. 2.7 +/- 0.2 mumol.kg fat 1.min-1, respectively). Upper body fat palmitate release was less (P less than 0.01) in LB Ob than Non Ob or UB Ob women (3.0 +/- 0.4 vs. 5.0 +/- 0.3 vs. 4.9 +/ 0.4 mumol.kg fat-1.min-1, respectively). Splanchnic palmitate release accounted for 20-32% of upper body fat palmitate release in each group (P = NS between groups). Leg fat palmitate release was significantly less than upper body fat palmitate release. We conclude that the major difference in resting FFA metabolism between UB Ob and LB Ob women is the ability of the later to down regulate upper body fat lipolysis to maintain normal FFA availability. PMID- 1864971 TI - The effects of infusion of insulinlike growth factor (IGF) I, IGF-II, and insulin on glucose and protein metabolism in fasted lambs. AB - In vivo effects of 300-min infusions of recombinant insulinlike growth factor I (IGF-I) and IGF-II on glucose and protein metabolism have been investigated in awake, fasted lambs. Two doses of recombinant human (rh) IGF-I were infused: 6.7 nmol/kg.h, which induced hypoglycemia, and 2.0 nmol/kg.h, which did not. The effects were compared with an insulin infusion (0.17 nmol/kg.h) that had the same hypoglycemic potential as the high dose rhIGF-I infusion. rhIGF-II was infused at a rate of 6.7 nmol/kg.h. Primed constant infusions of isotopically labeled glucose, urea and leucine tracers were used to determine glucose and protein kinetics. rhIGF-I lowered blood glucose by increasing the rate of glucose clearance (P less than 0.01), in contrast to insulin, which both increased clearance and reduced glucose production. Net protein loss was reduced after infusion of low and high dose rhIGF-I and insulin by 11% (P less than 0.05), 15% (P less than 0.01), and 12% (P less than 0.05), respectively. rhIGF-II infusion did not alter the rate of net protein loss. In contrast to insulin, high dose rhIGF-I infusion increased the rate of protein synthesis in skeletal (P less than 0.05) and cardiac muscle (P less than 0.01) and in hepatic tissue (P less than 0.05). We conclude that (a) protein metabolism is more sensitive than glucose metabolism to rhIGF-I infusion, as protein loss was reduced by an rhIGF-I infusion that did not alter glucose kinetics; (b) protein synthesis is increased by rhIGF-I infusion but not by insulin infusion; and (c) rhIGF-II is a less effective anabolic agent than rhIGF-I. We speculate that the effects of rhIGF-I on protein metabolism are not mediated by insulin receptors. PMID- 1864972 TI - Cationic Yersinia antigen-induced chronic allergic arthritis in rats. A model for reactive arthritis in humans. AB - Cationic antigens are known to have considerable arthritogenic potential in experimental systems. During a systematic search for suitable, naturally occurring candidates an intracellular protein was isolated from the ribosomal pellet of Yersinia enterocolitica 0:3, a bacterial strain associated with reactive arthritis in humans. The protein is highly cationic, contains two 19-kD polypeptide chains linked by a disulfide bond, and reveals a strong tendency for spontaneous aggregation. It is suggested to be a nucleic acid binding protein. We tested this antigen for its ability to induce arthritis after intra-articular challenge in preimmunized rats. An acute inflammatory phase followed by transition to chronicity was observed both by technetium-99m scintigraphy and from histology. Massive polymorphonuclear leucocyte infiltration of the synovium was seen early on and fibrosis and thickening of the joint capsule occurred in later stages. Control groups showed no evidence of inflammation. Western blot and ELISA analysis of unselected sera from Yersinia enterocolitica 0:3-infected patients revealed antibodies to the antigen in the majority of cases, whereas healthy individuals rarely reacted. This is the first report of a naturally occurring cationic antigen capable of inducing immunologic tissue injury; it justifies the speculation that cationic antigens from prokaryotic cells could trigger reactive arthritis in humans. PMID- 1864973 TI - Familial dysbetalipoproteinemia associated with apolipoprotein E3-Leiden in an extended multigeneration pedigree. AB - By the careful screening of familial dysbetalipoproteinemic (FD) patients, five probands showing heterozygosity for the APOE*3-Leiden allele were found. Genealogical studies revealed that these probands share common ancestry in the 17th century. In a group of 128 family members, spanning three generations, 37 additional heterozygous APOE*3-Leiden gene carriers were detected. Although with a variable degree of severity, all carriers exhibited characteristics of FD such as (a) elevated levels of cholesterol in the very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) fractions, (b) elevated ratios of cholesterol levels in these density fractions over total plasma levels of triglycerides, and (c) strongly increased plasma levels of apolipoprotein E (apoE). Multiple linear regression analysis revealed that most of the variability in expression of FD in APOE*3-Leiden allele carriers can be explained by age. Body mass index showed a less significant influence on the expression of FD. Gender had no effect on the expression in E*3-Leiden allele carriers, nor did it influence the age of onset of FD. In the group of APOE*3-Leiden allele carriers, we found that the E*2 allele enhances the expression of FD, whereas the E*4 allele had the opposite effect. Isoelectric focusing of plasma and of isolated VLDL, IDL, and high density lipoprotein density fractions showed that in E*3 Leiden allele carriers the apoE3-Leiden variant largely predominates over its normal apoE counterpart, especially in the VLDL and IDL density fractions. We conclude that in APOE*3-Leiden allele carriers FD is dominantly inherited with a high rate of penetrance, i.e., the presence of normally functioning apoE molecules in the plasma does not prevent the age-related expression of this disease. PMID- 1864974 TI - Taurine behaves as an osmolyte in Madin-Darby canine kidney cells. Protection by polarized, regulated transport of taurine. AB - Using a clonal growth assay, we demonstrated that taurine, a nonperturbing osmolyte accumulated in kidney medulla, brain, and some other tissues of hypertonic experimental animals can function as a nonperturbing osmolyte in Madin Darby canine kidney (MDCK) cells. The taurine content of hypertonic MDCK cells is twice that of isotonic MDCK cells (isotonic 160 nmol/mg protein; hypertonic 320 nmol/mg protein). Therefore we studied taurine transport in MDCK cells grown on porous supports and then studied the effect of hypertonicity which is known to elicit increased uptake of some other nonperturbing osmolytes by MDCK cells. Basal uptake exceeded apical uptake, with Km and Vmax of 56 microM and 933 pmol/min.mg protein on the basal surface and 10 microM and 50 pmol/min.mg protein on the apical surface. On both surfaces, virtually all taurine uptake was Na+ and Cl- dependent. 24 h after cells were shifted to hypertonic medium (500 mosmol/kg), taurine uptake doubled on the basolateral surface without change on the apical surface. The response to hypertonicity was the result of an increase in Vmax without change in Km. There was no change in taurine efflux when cells were shifted from isotonic to hypertonic medium. When cells adapted to hypertonic medium were shifted to isotonic medium, a large transient basolateral efflux of taurine occurred within 10 min. We conclude that taurine can function as a nonperturbing osmolyte in MDCK cells and that tonicity-regulated taurine transport is a basolateral function in MDCK cells. PMID- 1864975 TI - Acute lung injury. Pathogenesis of intraalveolar fibrosis. AB - In patients dying with acute lung injury, interstitial mesenchymal cells migrate into the airspace where they replicate and deposit connective tissue. We therefore hypothesized that peptides capable of promoting mesenchymal cell migration and replication would be present in the alveolar airspace. To examine this hypothesis, patients with severe acute diffuse lung injury (n = 26) underwent bronchoalveolar lavage. Acutely ill patients without lung injury served as controls (n = 12). Recovered effluent was examined for mesenchymal cell growth promoting and migration-promoting activity. Lavage cell supernates from both patients and controls were devoid of bioactivity. However, substantial growth promoting and migration-promoting activity was present in lavage fluid from nearly every patient, whereas little or none was present in fluid from controls. Characterization of the bioactivity indicated a significant proportion consisted of three peptides related to PDGF: (a) a 14-kD peptide that shared with PDGF several biophysical, biochemical, receptor-binding, and antigenic properties; (b) a 29-kD peptide that appeared identical to PDGF of platelet origin; and (c) a 38 kD peptide that was biophysically and antigenically similar to PDGF. These data indicate that peptide moieties are present in the airspace of patients after acute lung injury that can signal mesenchymal cell migration and replication. PMID- 1864976 TI - Oxygen-dependent lipid peroxidation during lung ischemia. AB - The effect of alveolar oxygen tension on lung lipid peroxidation during lung ischemia was evaluated by using isolated rat lungs perfused with synthetic medium. After a 5-min equilibration period, global ischemia was produced by discontinuing perfusion while ventilation continued with gas mixtures containing 5% CO2 and a fixed oxygen concentration between 0 and 95%. Lipid peroxidation was assessed by measurement of tissue thiobarbituric acid-reactive products and conjugated dienes. Control studies (no ischemia) showed no change in parameters of lipid peroxidation during 1 h of perfusion and ventilation with 20% or 95% O2. With 60 min of ischemia, there was increased lipid peroxidation which varied with oxygen content of the ventilating gas and was markedly inhibited by ventilation with N2. Perfusion with 5-, 8-, 11-, 14-eicosatetraynoic acid indicated that generation of eicosanoids during ischemia accounted for approximately 40-50% of lung lipid peroxide production. Changes of CO2 content of the ventilating gas (to alter tissue pH) or of perfusate glucose concentration had no effect on lipid peroxidation during ischemia, but perfusion at 8% of the normal flow rate prevented lipid peroxidation. Lung dry/wet weight measured after 3 min of reperfusion showed good correlation between lung fluid accumulation and lipid peroxidation. These results indicate that reperfusion is not necessary for lipid peroxidation with ischemic insult of the lung and provide evidence that elevated PO2 during ischemia accelerates the rate of tissue injury. PMID- 1864977 TI - Drug-induced anti-histone autoantibodies display two patterns of reactivity with substructures of chromatin. AB - Increasing evidence suggests that autoantibodies in the rheumatic diseases are a consequence of immune selection by self-material, but the nature of the in vivo immunogen is unknown. Insight into this problem may be obtained by measuring autoantibody binding to various forms of a target antigen. Antihistone antibodies arising as a side effect of therapy with various drugs offer an opportunity to explore this premise because many forms of histone have been characterized and adapted to ELISA formats. Two patterns of antibody reactivity were observed. All 21 patients with symptomatic procainamide-induced lupus and 7 of 12 patients with quinidine-induced lupus had IgG antibodies reacting predominantly with the (H2A H2B)-DNA complex and with chromatin. In contrast, antibodies in 19 of 24 patients taking procainamide without accompanying lupus-like symptoms did not show any pattern. The second pattern was observed in 18/19 chlorpromazine-treated patients and 14/17 patients with hydralazine-induced lupus in which IgM antibodies displayed more reactivity with DNA-free histones than with the corresponding histone-DNA complexes and almost no binding to H1-stripped chromatin. Absorption studies were entirely consistent with these results. Thus, the two patterns of reactivity with nucleosomal components reflect the molecular substructure of chromatin, suggesting that two processes underlie antihistone antibody induction by drugs. In one, IgG autoantibodies appear to be elicited by chromatin, whereas in the other, autoimmune tolerance to native chromatin appears largely intact, and IgM antibodies may be driven by DNA-free histone. PMID- 1864978 TI - Ionizing radiation induces expression and binding activity of the nuclear factor kappa B. AB - Recent studies have demonstrated that treatment of mammalian cells with ionizing radiation is associated with activation of gene expression. Although the signal transduction pathways stimulated by ionizing radiation remain unclear, our previous findings indicate that radiation induces specific genes at the transcriptional level. The present work has examined the effects of ionizing radiation on the transcription factor NF-kappa B. The results demonstrate that ionizing radiation activates DNA binding of nuclear factor (NF)kappa B. This effect was detectable at 2 grays (Gy) and reached a maximum at 5-20 Gy. At a dose of 20 Gy, the increase in NF-kappa B binding activity was maximal at 2-4 h and then declined to pretreatment levels. The results also demonstrate that ionizing radiation transiently increases NF-kappa B mRNA levels. However, the finding that induction of NF-kappa B binding to DNA occurs in the presence of cycloheximide indicates that ionizing radiation activates preexisting NF-kappa B protein. NF kappa B exists as a cytoplasmic protein before activation. Thus, our results suggest that ionizing radiation induces transduction pathways which include cytoplasmic signaling events. PMID- 1864979 TI - Interleukin-6 antisense oligonucleotides inhibit the growth of human myeloma cell lines. AB - IL-6 has been shown to be a plasmacytoma growth factor in mice and is believed to play a key role in the development of human multiple myeloma. We investigated the IL-6 requirements for the growth of two human myeloma cell lines, U 266 and RPMI 8226. These cell lines secreted minute amounts of IL-6 (20 U/ml) and featured IL 6 mRNA. IL-6 receptors were detectable at the surface of malignant cells by immunofluorescence. Antibodies to IL-6 did not alter the proliferation of these myeloma cells. There was a dose-dependent decrease, however, in [3H]-thymidine uptake in the presence of IL-6 antisense (and not sense) oligodeoxynucleotides; in the presence of 20 microM IL-6 antisense, an 80 and 95% inhibition of the proliferation of U 266 and RPMI 8226 cells was observed, respectively. These results provide strong evidence for an IL-6 autocrine proliferation of myeloma cells which may occur via internal interaction between IL-6 and the IL-6 receptor. PMID- 1864980 TI - Truncated forms of DNA-binding estrogen receptors in human breast cancer. AB - The likelihood a breast cancer will respond to antiestrogen therapy depends on the tumor content of immunoreactive or ligand-binding estrogen receptor (ER). To investigate the failure of many ER-positive breast cancers to respond to antiestrogen therapy, we examined by gel-shift assay the ability of tumor ER to bind its cognate estrogen response element (ERE). Analysis of 38 primary breast cancers showed that some tumors containing abundant immunoreactive ER failed to demonstrate DNA binding ER. In many other ER-positive tumors, the fraction of DNA binding ER was low and consisted primarily of truncated receptor forms, which on Western analysis were revealed to be 50 kD homodimers and 67-50 kD ER heterodimers. The use of protease inhibitors during tumor extraction and the demonstration of nuclear-localizing ER and ERE-binding COUP (chicken ovalbumin upstream promoter) protein in these tumors indicated that the truncated forms of ER were likely present in vivo. The presence of intact DNA binding ER correlated with higher tumor content of immunoreactive sex steroid receptors (ER and/or PR), standard predictors of tumor responsiveness to antiestrogen, suggesting that loss or truncation of DNA binding ER may be an important prognostic parameter accounting for some forms of clinical resistance to antiestrogen therapy. PMID- 1864981 TI - Recapitulation of normal and abnormal BB rat immune system development in scid mouse/rat lymphohemopoietic chimeras. AB - Mice homozygous for the mutation "severe combined immune deficiency" (C.B17 scid/scid) lack functional T and B lymphocytes and readily accept tumor xenografts. Partial lymphohemopoietic scid/human and mouse/rat chimeras have been described, but complete chimerization with thymic engraftment and generation of donor-origin thymocytes has not been achieved. We now report that low-dose irradiation permits the engraftment of BB rat fetal liver stem cells in scid recipients. We observed that BB rat fetal liver cells injected into irradiated scid mice establish a rat hemopoietic system in the scid mouse bone marrow and populate the scid mouse thymus. These stem cells generated rat-origin thymocytes that migrated to the scid mouse spleen, a peripheral lymphoid organ. Finally, we found that xenogeneic chimeras created using fetal liver cells from the abnormal (lymphopenic, diabetes prone) subline of BB rats recapitulated both the quantitative and phenotypic abnormalities of the donor rat. Xenogeneic lymphohemopoietic chimeras established in scid mice may provide a powerful new tool in the study of immune system development and autoimmunity. PMID- 1864982 TI - Macrophages, microglial cells, and HLA-DR antigens in fetal and infant brain. AB - Immunohistochemical reactions for macrophages, microglia, and HLA-DR antigens were tested on frozen sections of necropsy brain tissue from 20 fetuses and infants ranging in age from 18 weeks' gestation to 8 months post term. No primary central nervous system disease was present but there were four cases of sudden infant death syndrome (SIDS). Macrophages were detected in all the samples studied and were located in the germinal matrix zone, in perivascular spaces throughout the brain, and in the leptomeninges and subependymal layer. Well differentiated microglia were present in all cases examined after 35 weeks' gestation and less well ramified forms were seen at earlier stages of gestation. HLA-DR antigens were detected on a small number of macrophages, chiefly in a perivascular location, in all but three cases. The fewest reactive cells and the weakest reactions occurred in the youngest fetuses. One case of SIDS showed increased foci of microglia in perivascular white matter: this case and one other case of SIDS were the only cases with well ramified microglia that expressed HLA DR antigens. These findings may be relevant to an understanding of local immune responses in fetal brain infections, including human immunodeficiency virus infection. PMID- 1864983 TI - Class I and class II major histocompatibility complex antigens on hepatocytes: importance of the method of detection and expression in histologically normal and diseased livers. AB - Methodological differences in major histocompatibility complex (MHC) antigen detection were investigated on isolated, viable hepatocytes and cryostat hepatic sections from 27 children with liver disorders, six of whom had normal histology. Class I antigens were constantly found on sections using a three step immunoperoxidase technique after acetone/chloroform fixation, other techniques being less sensitive, or on isolated hepatocytes by indirect immunofluorescence alone. With mechanical isolation the percentage of positivity ranged from 85 to 100%, while with collagenase isolation it ranged from 22 to 49% on immediate testing, and from 53 to 80% after 24 hour incubation. Class II antigens were only detected in one patient with autoimmune chronic active hepatitis and two with primary sclerosing cholangitis. Flow cytofluorimetric analysis in 11 cases confirmed class II or class I positivity, or both, on isolated hepatocytes, allowing MHC antigen expression on hepatocytes to be measured. Class I and II antigen detection on hepatocytes is influenced by the technique used. Although class I antigens are invariably expressed on hepatocytes, class II antigens are only found on hepatocytes from patients with immune mediated liver disorders. PMID- 1864984 TI - Comparison of a modified thiazole orange technique with a fully automated analyser for reticulocyte counting. AB - Two independent methods for quantitating reticulocyte counts were compared. One used a modified thiazole orange technique and a flow cytometer (Becton Dickinson FACS); the other was a fully automated whole blood analyser (Sysmex R1000). Both methods gave comparable results with a coefficient of variation of less than 5%. Samples measured using the R1000 showed a negligible decrease in the reticulocyte count over five days at room temperature, although there was evidence of continuing intracellular maturation: with thiazole orange there was an apparent increase. A practical reference range of 20-70 x 10(9)/l was established from 89 normal subjects. The close correlation between the two independent estimates indicates the validity of the quantitation of the reticulocyte count and shows that automation allows significant changes within and below the normal range to be detected with a degree of reliability which was not previously possible. PMID- 1864986 TI - Distribution of plasminogen activator inhibitor (PAI-1) in tissues. AB - Extracts of human tissue were analysed for plasminogen activator inhibitor (PAI 1) antigen and activity. PAI-1 was localised in tissues by an immunochemical method, using monoclonal antibodies. PAI-1 occurred throughout the body; its concentration and activity differed considerably from organ to organ. Extracts of liver and spleen had the greatest abundance of PAI-1, but the activity of the inhibitor was much higher in liver than in spleen: the liver may be a source of plasma PAI-1. Immunochemical staining for PAI-1 was observed in endothelium, platelets and their precursor cells, the megakaryocytes, and locations central to the process of haemostasis. PAI-1 also occurred in neutrophil polymorphs and macrophages, cells important in inflammatory and immune processes, but not in lymphocytes. Other cell types, in particular, vascular smooth muscle cells and mesangial cells, also stained positively for PAI-1 and such cells seem to represent an important reservoir of PAI-1. PMID- 1864985 TI - Globin chain synthesis in myelodysplastic syndromes. AB - Globin chain synthesis was studied in the reticulocytes of 30 patients with various myelodysplastic syndromes (MDS) to determine the alpha:beta globin chain synthetic ratio and its probable prognostic value. The mean (SD) value of the total alpha:beta ratio was 0.82 (0.45) ranging from 0.05 to 1.73. The same ratio in 10 normal controls was 1.01 (0.04). This difference was significant. Furthermore, the alpha:beta ratios were lower than normal in 14 patients (alpha thalassaemia-like) (group I), almost within normal limits in 11 (group II), and higher than normal in five (beta-thalassaemia-like) (group III). In each group almost all the FAB subtypes were represented. The addition of exogenous haem in several of the test samples resulted in a slight to pronounced increase in the alpha:beta ratios, particularly in group I. In 92% of the high risk cases (refractory anaemia with excess blasts (RAEB), chronic myelomonocytic leukaemia (CMML] or 87.5% of patients who finally developed acute non-lyphoid leukaemia (ANLL) low or normal alpha:beta ratios were found. No significant correlation was noticed between alpha:beta ratios and various haematological variables or survival. It is concluded that in MDS the alpha:beta ratio varied enormously across the entire population of patients, as well as within each FAB subtype, thereby restricting its prognostic value. Although haem deficiency may be implicated in some cases of MDS, why this should be remains unclear. PMID- 1864987 TI - Comparison of image analysis and flow cytometric determination of cellular DNA content. AB - A good correlation (r = 0.94) was obtained between the DNA indices (DI) using flow cytometry and image analysis of nuclei cytospins extracted from paraffin wax embedded tumour sections. Some of the limitations and problems associated with image analysis which came to light included an unacceptably high coefficient of variation (CV) and a "left-shift" in the DI in most DNA histograms obtained when using image analysis of 5 microns sections. In contrast, the DNA histograms generated using image analysis of cytospun nuclei from paraffin wax blocks were of good quality and similar to those obtained using flow cytometry. Variability in Feulgen staining was common and an important source of error despite rigorous control of the staining technique. This could be overcome by using internal controls such as fibroblasts rather than external controls (rat hepatocytes) to determine the diploid DI with image analysis. A thorough understanding and appreciation of the methodological problems associated with image analysis and flow cytometric determination of DNA content is required before these methods find widespread clinical application. PMID- 1864988 TI - Harnessing of urease activity of Helicobacter pylori to induce self-destruction of the bacterium. AB - Eradication of Helicobacter pylori with currently available antibacterial agents is unsatisfactory due to the risk of side-effects and the emergence of resistance. The organism rapidly dies in vitro in the presence of urea at pH 6. When incubated in citrate buffer (pH 6) plus urea (10 mM) the five minute survival was 26% compared with 96% without urea and the survival progressively decreased with increasing urea concentrations, being only 9% in 50 mM urea. The bactericidal effect depended on pH as the organism survived in citrate buffer (pH 7) plus urea (50 mM). The death of the organism at pH 6 in the presence of urea was prevented by the addition of the competitive urease inhibitor hydroxyurea. These findings indicate that destruction of the organism is mediated by its exceptionally high urease activity. Harnessing this enzyme to induce self destruction could provide a new approach to eradicating this common infection. PMID- 1864989 TI - Incidence of penicillin tolerance among blood culture isolates of Streptococcus sanguis, 1987-88. AB - Laboratories that reported isolations of Streptococcus sanguis from blood cultures to the Communicable Disease Surveillance Centre (CDSC) Colindale were requested to submit strains to Bath Public Health Laboratory to allow the prevalence of penicillin tolerance within different biotypes of this species to be studied. One hundred and fifty one Streptococcus spp were received from 78 United Kingdom laboratories in one year. Strains were identified using the API 20 Strep, and minimum inhibitory concentrations (MICs) of penicillin were determined using the spiral gradient plate method. Penicillin tolerance was detected by spraying beta-lactamase over inoculated gradient plates, reincubating for 48 hours and counting the number of surviving organisms represented by colonies. There were 57 different API identification profiles encountered in the survey. Most S sanguis I/1 strains were penicillin tolerant, most S sanguis II strains were non-tolerant. The overall geometric mean MIC of penicillin was considerably lower for S sanguis I/1 than for all other biotypes. The distribution of biotypes and the geometric mean MIC of penicillin for each biotype were not significantly different for infective endocarditis strains than for all strains tested, suggesting little or no association between penicillin tolerance and the seeding of endocardium. When the reactions obtained using API 20 Strep were compared with a recent taxonomic study of viridans streptococci, 22 of 38 S sanguis I/1 strains could be reclassified as S gordonii; all these strains were penicillin tolerant. Such reclassification would allow likely penicillin tolerant strains to be predicted. PMID- 1864990 TI - What's in a burger? AB - In an attempt to confirm the presence or absence of central nervous tissue in commercially prepared beefburgers, four burgers were processed and stained using routine histological laboratory techniques. Constituent parts of the burgers could be identified readily. In this small sample no central nervous tissue was found. There is currently considerable general interest in the contents of foodstuffs, particularly now that certain specified bovine offals as well as central nervous tissue have been banned from human consumption. Conventional histological techniques may be of value in analysing the ingredients of beef products. PMID- 1864991 TI - The need for primary quality control of commercially available immunoassay kits. AB - Discrepancies among three commercially available luteinising hormone (LH) radioimmunoassay RIA kits, all calibrated against the second-IRP-HMG (World Health Organisation International Laboratory for Biological Standards), were observed. Even though the Japan Radioisotope Association carries out external quality control in Japan every year, inaccuracies still exist. This problem also exists elsewhere, and it is proposed that a global monitoring system of primary quality control (PQC) should be introduced by a body such as the World Health Organisation. PMID- 1864992 TI - Helicobacter pylori serology using specimens collected on filter paper. AB - A simple method for the collection of blood specimens on filter paper for serology of Helicobacter pylori was devised. Blood was freshly applied to small Whatman 3 mm filter paper and allowed to dry. Serological activity, as measured by reactivity to H pylori antigens (AMRAD, Australia), was retained after storage for one month at both room temperature and at 4 degrees C. This technique eliminates formal venepuncture, separation of sera, and arduous packaging of specimens to be sent to the laboratory. PMID- 1864993 TI - Examination of spinal cord in diseases of the craniocervical junction and high cervical spine. AB - A simple necropsy technique for the removal of the craniocervical junction was devised: a relatively small specimen comprising part of the clivus, the foramen magnum, and cervical vertebral canal is removed in one piece with the medulla and spinal cord inside, and examined systematically after fixation. This method, used in a series of patients with chronic craniocervical instability, allows both good clinicopathological correlations to be made and histological changes in the lower medulla or upper cervical cord segments to be related to sites of extrinsic compression. PMID- 1864994 TI - Royal College of Pathologists' accreditation pilot study: a year later. The College Audit Steering Committee. AB - Twenty one heads of departments who participated in the Royal College of Pathologists' pilot study of laboratory accreditation were questioned a year after the event to discover if the process had produced any lasting effect. All but one responded. Eighteen (90%) felt that there had been lasting and tangible benefit from their inspection. Of 10 departments with deficiencies relating to resources (and where no plans to upgrade existed before the study), five (50%) had obtained improvements as a direct result of the inspector's report. Overall, 16 (80%) of respondents were in support of the development of an accreditation scheme of the type attempted, and none were opposed. The envisaged scheme seems to have the potential to produce lasting improvements in service and commands the support of the departments involved so far. PMID- 1864995 TI - Modification of the alcian blue method for marking breast biopsy specimens. PMID- 1864996 TI - Immunoalkaline phosphatase technique in renal pathology. PMID- 1864997 TI - Laboratory handling of impalpable breast lesions: a review. PMID- 1864998 TI - Early clinical pathologists: 3. Sidney Campbell Dyke. PMID- 1864999 TI - Localization of NADPH-diaphorase-containing neurons in sensory ganglia of the rat. AB - The presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity was studied histochemically in the sensory ganglia of the rat. Supraspinally, the trigeminal ganglion possessed only a few cells positively stained for NADPH-diaphorase, while a large number of positive neurons was found in the nodose ganglion. In the dorsal root ganglia, the distribution of positive cells showed a peculiar pattern in relation to spinal levels. Very minor populations (less than 2% of the total ganglionic cells) exhibited positive reaction in ganglia at levels ranging from the first cervical (C1) to fourth thoracic (T4) and from the second lumber (L2) through the entire sacral levels. In the middle to lower thoracic levels (from T5 to L1), however, abundant diaphorase-positive cells were observed. From these positive neurons it was possible to trace intensely stained nerve fibers. In the lower thoracic level, for example, dense positive fibers were seen in the ramus communicans. Retrograde tracing studies revealed that diaphorase-containing neurons in the lower thoracic level project at least partly to the gastric wall and the celiac ganglion. These results indicate that the diaphorase-positive ganglionic neurons in the thoracicolumbar levels may carry autonomic visceral afferent information. Double staining with NADPH-diaphorase histochemistry and peptide immunohistochemistry revealed that NADPH-diaphorase colocalizes with calcitonin gene-related peptide and substance P in many of these visceral afferent neurons. PMID- 1865000 TI - Neurofilament antibodies and spiral ganglion neurons of the mammalian cochlea. AB - The spiral ganglia of the cat, gerbil, mouse, rat, and human were immunohistochemically stained with various monoclonal neurofilament antibodies. Three antibodies to the 200-kD neurofilament protein (R-3, Drager et al., '84; ICN anti-200, clone NE14, Debus et al., '83; RT-97, Wood and Anderton, '81) labeled the somata of type II spiral ganglion neurons but not those of type I ganglion neurons. In the extreme base of the cochlea of cats, mice and rats, there was intense labeling of a few (less than 0.5% of the total ganglion population) large neurons resembling type I ganglion neurons. Several other neurofilament antibodies (Amersham anti-68, Amersham and ICN anti-160, and SMI 32) did not specifically label type II ganglion neurons but instead labeled all neurons of the spiral ganglion. These two patterns of labeling prompted us to investigate the cause for this difference. Because antibodies against the 200-kD neurofilament protein preferentially labeled type II neurons and because 200-kD neurofilament is highly phosphorylated, we treated cochlear tissue with alkaline phosphatase in order to remove phosphate groups. This treatment eliminated the intense labeling of type II neurons with R-3, ICN anti-200, and RT-97, but had no effect on the intense labeling of ganglion cell bodies observed with the other neurofilament antibodies tested. This evidence suggests that labeling occurs because of the cytoplasmic presence of phosphorylated 200-kD neurofilament protein in type II ganglion neurons. Populations of neurons may thus differ in their neurofilament epitopes and monoclonal antibodies can be used to mark such differences. PMID- 1865001 TI - Axonal regeneration in the adult lamprey spinal cord. AB - Larval sea lampreys recover from complete spinal transection by a process involving directionally specific axonal regeneration. In order to determine whether this is also true of adults, 14 adult lampreys were transected at the level of the 5th gill and allowed to recover for 10 weeks. Muller and Mauthner cells and their giant reticulospinal axons (GRAs) were impaled with microelectrodes and injected with horseradish peroxidase (HRP). The tissue was processed for HRP histochemistry and wholemounts of brain and spinal cord were prepared. All animals recovered coordinated swimming; 61 of 121 (50%) neurites emanating from 30 axons regenerated caudal to the scar into the distal stump. Of the neurites which had grown beyond the scar, 92% were correctly oriented, i.e., caudalward and ipsilateral to the parent axon. Retransection in two additional animals eliminated the recovered swimming. Thus, behavioral recovery in adult sea lampreys is accompanied by directionally specific axonal regeneration. PMID- 1865002 TI - SCPB-and FMRFamide-like immunoreactivities in lobster neurons: colocalization of distinct peptides or colabeling of the same peptide(s)? AB - Virtually all of the SCPB-like immunoreactive neurons (ca. 60 cells) in the lobster Homarus americanus also contain FMRFamide-like immunoreactivity. Control experiments reveal that SCPB-and FMRFamide-like immunoreactivities are successfully preadsorbed with their specific antigens, while the normal staining pattern is retained following preadsorption of each antibody with the alternate peptide. These experiments potentially lead to the conclusion that the anti-SCPB and anti-FMRFamide antibodies are labeling distinct compounds that are colocalized in lobster neurons. The lobster nervous system does not, however, contain authentic FMRFamide, but rather several FMRFamide-like compounds (Trimmer et al., J. Comp. Neurol. 266:16-26, 1987). The most abundant of these is the octapeptide TNRNFLRFamide. Experiments demonstrate that SCPB-like immunoreactivity is completely preadsorbed with synthetic TNRNFLRFamide, while there is a significant or complete loss of staining after preadsorption of the FMRFamide antibody with this molecule. Met-enkephalin-Arg-Phe-amide (YGGFMRFamide), an extended opioid peptide containing the FMRFamide sequence, also preadsorbs SCPB- and FMRFamide-like immunoreactivities, while Met-enkephalin Arg-Phe (YGGFMRF) has no effect on the staining properties of these antibodies. These results suggest that the SCPB antibody can bind to extended forms of FMRFamide-like molecules, and that anti-SCPB and anti-FMRFamide antibodies may be colabeling one or more FMRFamide-like molecules in lobster neurons. PMID- 1865003 TI - Nerve growth factor mRNA-containing cells are distributed within regions of cholinergic neurons in the rat basal forebrain. AB - It has been proposed that nerve growth factor (NGF) provides critical trophic support for the cholinergic neurons of the basal forebrain and that it becomes available to these neurons by retrograde transport from distant forebrain targets. However, neurochemical studies have detected low levels of NGF mRNA within basal forebrain areas of normal and experimental animals, thus suggesting that some NGF synthesis may actually occur within the region of the responsive cholinergic cells. In the present study with in situ hybridization and immunohistochemical techniques, the distribution of cells containing NGF mRNA within basal forebrain was compared with the distribution of cholinergic perikarya. The localization o NGF mRNA was examined by using a 35S-labeled RNA probe complementary to rat preproNGF mRNA and emulsion autoradiography. Hybridization of the NGF cRNA labeled a large number of cells within the anterior olfactory nucleus and the piriform cortex as well as neurons in a continuous zone spanning the lateral aspects of both the horizontal limb of the diagonal band of Broca and the magnocellular preoptic nucleus. In the latter regions, large autoradiographic grain clusters labeled relatively large Nissl-pale nuclei; it did not appear that glial cells were autoradiographically labeled. Comparison of adjacent tissue sections processed for in situ hybridization to NGF mRNA and immunohistochemical localization of choline acetyltransferase (ChAT) demonstrated overlapping fields of cRNA-labeled neurons and ChAT immunoreactive perikarya in both the horizontal limb of the diagonal band and magnocellular preoptic regions. However, no hybridization of the cRNA probe was observed in other principal cholinergic regions including the medial septum, the vertical limb of the diagonal band, or the nucleus basalis of Meynert.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865004 TI - Organization of nucleoli and nuclear bodies in osmotically stimulated supraoptic neurons of the rat. AB - This study has analyzed variations in the number of nucleoli and nuclear bodies, as well as in their ultrastructural and cytochemical organization, after the osmotically induced activation of supraoptic nucleus (SON) neurons of the rat. The number of nucleoli and nuclear bodies and also the nucleolar size were determined on smear preparations of previously block-impregnated SON. The mean number of nucleoli per cell was 1.35 +/- 0.6 (mean +/- SDM) in control rats. No significant variations in this value were registered either in dehydrated or rehydrated rats. The mean nucleolar volume and the total nucleolar volume per cell showed a significant increase in dehydrated rats with respect to the controls, whereas these two parameters tended to return to control values in rats rehydrated after dehydration. The mean number of nuclear bodies per cell increased significantly from 0.56 +/- 0.50 (mean +/- SDM) in control rats to 1.54 +/- 1.1 after 6 days of dehydration. By electron microscopy, SON neurons displayed a reticulated nucleolar configuration. After the osmotically induced neuronal activation, there was an increase in the proportion of the total nucleolar area occupied by the granular component, and also a reduction in the mean fibrillar-center area. The most characteristic nucleolar features in rehydrated rats were the tendency for the granular component to be segregated and the occurrence of intranucleolar vacuoles. Ultrastructural cytochemistry with a specific silver method revealed a selective silver reaction on the coiled threads of the nuclear bodies--identified as "coiled bodies"--and on the nucleolar fibrillar components in all animal groups studied. Since nucleoli play a major role in ribosome biogenesis, a relationship between these nucleolar changes and the level of cellular activity of SON neurons is proposed. Furthermore, the response of nuclear "coiled bodies" to neuronal activation suggests their participation in the processing and transport of rRNA precursors. PMID- 1865005 TI - Mapping of glial fibrillary acidic protein-immunoreactivity in the rat forebrain and mesencephalon by computerized image analysis. AB - Computer-assisted image analysis was used to map the regional distribution of glial fibrillary acidic protein-immunoreactive (GFAP-IR) astrocytes in the rat forebrain and mesencephalon. A complete survey of packing densities of GFAP-IR structures was performed. Computer maps revealed high values in the outer and inner layers of the cortex, some hippocampal and olfactory bulb layers, prepiriform cortex, dorsal part of the caudate-putamen, globus pallidus, lateral septum, reticular thalamic nucleus, lateral habenular nucleus, circumventricular organs, nuclei of the medial hypothalamus, substantia nigra, interpeduncular nucleus, and mamillary body. These correspond to regions of the embryonic pial and ventricular brain surfaces, which undergo developmental alterations including growth and various forms of internalization. From this we conclude that in the adult brain, astrocytes of high GFAP-IR are derivatives of surface-contact glia, whereas those located in areas having developed by the local thickening of the neural tube wall show reduced or no GFAP-IR. PMID- 1865006 TI - Rod and cone specific domains in the interphotoreceptor matrix. AB - The insoluble matrix domain of the interphotoreceptor matrix (IPM) from normal dog, cat, and mouse retinae were characterized using lectin cytochemistry. The lectins WGA (wheat germ agglutinin) and PNA (peanut agglutinin) were used to label interphotoreceptor matrix microdomains in cryosections of retinal tissue and in extracted insoluble matrix. Retinal cryosections and extracted matrix were examined by epifluorescence microscopy and scanning confocal laser microscopy, the latter allowed for the removal of all background fluorescence and gave increased resolution. The insoluble matrix was extracted as a continuous sheet that was comprised of two photoreceptor-specific matrix domains distinguished both by the size of the domains, and by differential binding of WGA and PNA lectins. Each domain encloses a photoreceptor inner and outer segment. Individual rod-associated domains were connected into a hexagonal lattice and this pattern was regularly interrupted by the larger cone-associated domains which have 8-10 surrounding rod domains. The PNA lectin primarily labeled the cone-associated matrix with faint binding to the rod matrix; the WGA lectin labeled both the rod- and cone-associated matrix. PMID- 1865008 TI - Histochemical demonstration of zinc in the hippocampal region of the domestic pig: III. The dentate area. AB - The distribution of zinc was described in the dentate area, a part of the hippocampal region, of the domestic pig. A modification of Timm's sulphide silver procedure, the Neo-Timm method, was used for the histochemical demonstration of zinc. The staining of the dentate area exhibited a well-defined stratified pattern, the predominant part of the staining being restricted to the neuropil, although weakly stained nerve cell bodies were observed in the hilus fasciae dentatae. In the molecular layer, three distinct sublaminae were seen at most septotemporal levels. The outer and inner sublaminae displayed medium staining intensity, whereas the intermediate sublamina appeared extremely pale. The granular cell layer was well stained in its superficial two thirds, because of dense masses of staining occupying the interstices between the unstained granular cells. In the hilus fasciae dentatae, extreme differences in staining intensity were seen between the layers, ranging from very intense staining of the outer hilar cell layer to generally weak staining of the inner plexiform layer. The distribution of zinc in the pig was compared with that in the guinea pig and rat, described previously. The staining pattern of the molecular layer showed striking species differences, whereas the granular cell layer appeared very near identical. The stratified staining pattern seen in the hilus of the pig is very similar to the distribution observed in the guinea pig, but differs from the essentially homogeneous staining of the rat hilus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865007 TI - Calcium-binding protein (calbindin-D28K) and parvalbumin immunocytochemistry in the normal and epileptic human hippocampus. AB - The calcium-binding proteins calbindin-D28K (CaBP) and parvalbumin (PV) were localized in the "normal" and "epileptic" human hippocampus to address the possible relationship between the expression of these constitutive cytosolic calcium-binding proteins and the resistance or selective vulnerability of different hippocampal neuron populations in temporal lobe epilepsy. Compared to rodents and a baboon (Papio papio), the pattern of CaBP-like immunoreactivity (LI) in the "normal" human hippocampus is unique. CaBP-LI is present in the dentate granule cells, neurons of the "resistant zone" (area CA2), and presumed interneurons of all regions. Unlike rodent and baboon CA1 pyramidal cells, human CA1 pyramidal cells appear to be devoid of CaBP-LI. Thus, the relatively resistant dentate granule cells and CA2 pyramidal cells are the only human hippocampal principal cells that contain CaBP-LI normally. As in lower mammals, PV-LI is present exclusively in interneurons of all human hippocampal subregions. CaBP- and PV-LI were localized in hippocampi surgically removed in the treatment of intractable temporal lobe epilepsy to determine whether surviving hippocampal cells were those that express these calcium-binding proteins. Hippocampi removed from patients with tumors or arteriovenous malformations that were associated with complex partial seizures arising from this region appeared relatively normal histologically. CaBP- and PV-LI in this patient group appeared similar to that seen in autopsy controls. Conversely, "cryptogenic" epileptics, who exhibit hippocampal sclerosis as the only lesion associated with the epilepsy, exhibited a preferential survival of hippocampal cells that were CaBP- or PV immunoreactive. In the dentate hilus, which normally contains few CaBP-LI neurons, most of the few surviving hilar neurons were CaBP-immunoreactive. Their number and darkness of staining suggests that CaBP synthesis may be increased in cells that survive. Despite an obvious decrease of PV-LI specifically in the damaged parts of the sclerotic hippocampi, PV-immunoreactive interneurons were often among the few surviving cells. Nevertheless, large expanses of the surviving granule cell layer appeared to have lost the PV-immunoreactive axosomatic fiber plexus. These results reveal a unique and striking correlation between the human hippocampal cells that normally express these calcium-binding proteins and those that survive in the sclerotic epileptic hippocampus. PMID- 1865009 TI - Central projections of cervical primary afferent fibers in the guinea pig: an HRP and WGA/HRP tracer study. AB - The central course and the projections of the first and the second cervical dorsal root ganglia and of suboccipital muscle primary afferent fibers in the guinea pig were studied by means of anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA/HRP) or aqueous solution of horseradish peroxidase (HRP). Injections of WGA/HRP into the second cervical dorsal root ganglion produced labeling in the dorsal and ventral horns. Within the spinal cord, the largest amount of HRP reaction product was found within the lateral third of the substantia gelatinosa and within the central cervical nucleus. The main area of termination in the medulla was the external cuneate nucleus. However, HRP reaction product was also found within the medial and inferior vestibular nuclei, cell group x, the perihypoglossal nuclei, the nucleus of the solitary tract, and the nucleus of the spinal trigeminal tract. Descending fibers could be detected as caudal as spinal segment T5. Injections of WGA/HRP into the first cervical dorsal root ganglion produced heavy terminal label within the central cervical nucleus but not within the substantia gelatinosa. Again, the external cuneate nucleus was the main area of termination within the medulla. Label could not be observed within the vestibular nuclear complex or within the spinal trigeminal nucleus. Injections of aqueous HRP into the suboccipital muscles produced heavy transganglionic label within the central cervical nucleus, whereas the substantia gelatinosa totally lacked terminal label. Ascending proprioceptive fibers reached the external cuneate nucleus and group x. Scanty projections could be detected within the vestibular nuclei as well as within the perihypoglossal nuclei except for the nucleus prepositus hypoglossi. Label was absent in the spinal trigeminal nucleus. PMID- 1865010 TI - Patterns of sensory intermodality relationships in the cerebral cortex of the rat. AB - Patterns of connections underlying cross-modality integration were studied by injecting distinguishable, retrograde tracers (Fluoro-Gold and diamidino yellow) in pairwise manner into different sensory representations (visual, somatosensory, and auditory) in the cerebral cortex of the rat. In agreement with previous single tracer studies, our results indicate that the central core of sensory areas receives projections mainly from a set of association areas located in a ringlike fashion along the margin of the cortical mantle. The visual cortex received projections from areas 48/49, area 29d, posterior agranular medial cortex (AGm), area 11, area 13, and area 35. All these areas were also connected to the auditory cortex with the exception of areas 29d and AGm. However, lateral to area 29d and posterior AGm, a band of neurons projecting to the auditory cortex was present. Somatosensory cortex was connected mainly with the more anterior aspect of the hemisphere, which included primary motor area, area 11, and area 13. The patterns of intermodality relationships revealed in the present study were of two main categories. In the anterior and lateral areas, an intermingling of cells projecting to different sensory modalities was observed. In contrast, in areas located along the medial aspect of the hemisphere, cells connected to different sensory modality representations tended to be segregated from each other. Postsubicular cortex (areas 48/49) contained both intermingled and segregated groups of cells. The incidence of clearly identified double labeled cells concurrently projecting to two different sensory representations was extremely rare. These patterns may form a substrate for different levels of cross-modal sensory integration in the rat cortex. PMID- 1865011 TI - Cortical areas in the medial frontal lobe of the cat delineated by quantitative analysis of thalamic afferents. AB - The aim of these experiments was to establish the number and location of connectionally distinct areas in the medial frontal lobe of the cat. Thirty deposits of distinguishable retrograde tracers were placed at restricted sites spanning the medial frontal lobe in 16 cats. Following each deposit, the number of retrogradely labeled neurons in each of 17 thalamic nuclei was determined. Variations of the thalamic labeling pattern dependent on the location of the cortical tracer deposit were then analyzed by a quantitative procedure. The results indicate that the medial frontal lobe contains three fundamental divisions: the anterior cingulate area, medial area 6, and the medial prefrontal district. The anterior cingulate area derives its strongest thalamic input from the anteriomedial nucleus. Medial area 6 is the target of afferents originating in a dorsolateral sector of the mediodorsal nucleus and in the ventroanterior nucleus. Medial prefrontal cortex is heavily innervated by pathways originating in the core of the mediodorsal nucleus and in the principal ventromedial nucleus. Within each major district, thalamic connectional patterns exhibit graded regional variation, with the result that, whereas the connections of the district are not uniform, it is difficult to define further discrete subdivisions. We discuss these results in relation to previously proposed schemes for paracellation of the cat's medial frontal lobe and conclude that the infralimbic and prelimbic areas (areas 25 and 32) of previous systems are best understood not as discrete areas but as ventral and intermediate sectors of a continuous medial prefrontal domain. PMID- 1865012 TI - Anatomic evidence of nociceptive inputs to primary somatosensory cortex: relationship between spinothalamic terminals and thalamocortical cells in squirrel monkeys. AB - This study examined anatomic pathways that are likely to transmit noxious and thermal cutaneous information to the primary somatosensory cortex. Anterograde and retrograde labeling techniques were combined to investigate the relationship between spinothalamic (STT) projections and thalamocortical neurons in the squirrel monkey (Saimiri sciureus). Large injections of diamidino yellow (DY) were placed in the physiologically defined hand region of primary somatosensory cortex (hSI), and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected in the contralateral cervical enlargement (C5-T1). Both DY-labeled neuronal cell bodies and HRP-labeled STT terminal-like structures were visualized within single thalamic sections in each animal. Quantitative analysis of the positions and numbers of retrogradely labeled neurons and anterogradely labeled terminal fields reveal that: 1) ventral posterior lateral (VPL), ventral posterior inferior (VPI), and central lateral (CL), combined, receive 87% of spinothalamic inputs originating from the cervical enlargement; 2) these three nuclei contain over 91% of all thalamocortical neurons projecting to hSI that are likely to receive STT input; and 3) these putatively contacted neurons account for less than 24% of all thalamic projections to hSI. These results suggest that three distinct spinothalamocortical pathways are capable of relaying nociceptive information to the hand somatosensory cortex. Moreover, only a small portion of thalamocortical neurons are capable of relaying STT-derived nociceptive and thermal information to the primary somatosensory cortex. PMID- 1865013 TI - Synaptogenesis in the primary visual cortex of the tree shrew (Tupaia belangeri). AB - The primary visual cortex of the tree shrew is characterized by the lack of ocular dominance columns. The two eyes are represented in sublayers of laminae 3 and 4. In an earlier study using the transneuronal transport we observed that the geniculate afferents from the two eyes do not initially overlap and then segregate into their appropriate sublaminae. The final distribution pattern can already be observed during the early postnatal period. Since segregation and elimination of afferent terminal branches do not seem to take place, we wanted to investigate whether or not an overproduction of synapses can be observed as in several other animals. We examined layers 3B, 3C, 4A, and 4B, which receive afferents from the retina via the lateral geniculate nucleus, from P5 to maturity by using the electron microscope. The brain tissue was excised in the region where the central vision is represented in adult animals. Then we determined the density of synapses per 100 microns 2 neuropil for each of the four sublayers at the ages P5, P15, P19, P23, P31, and P42 and in the adult animal (AD). In determining the neuropil we measured the size of two additional compartments, i.e., the compartments consisting of perikarya and of blood vessels. At a higher resolution we determined the fraction of Gray type I and type II synapses in each sublamina and in each developmental stage. The size of the neuropil increases from 57% at P5 to 81% in AD whereas the compartment of perikarya decreases from 42% to 15% and the compartment of blood vessels increases from 1.3% to 3.9%. The synaptic density starts with very low values (3.5/100 microns 2) at P5. Then it increases rapidly and attains a maximal rate of increase during the period of eyelid opening. After this period the increase is slowed down and approaches the adult value (12.5/100 microns 2) slowly. An overproduction of synapses could not be observed. The percentage of type I and type II synapses also changes during this period. The fraction of type I synapses amounts to 73% at P5 and increases to 92% in AD. The increase in density of type I synapses is continuous and does not show any sign of overproduction. The density of type II synapses rapidly reaches it final value and then remains constant. Possibly there is a slight overproduction during the period of eyelid opening.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1865014 TI - Musculotopic organization of the hypoglossal nucleus in the grass frog, Rana pipiens. AB - Recent neural tracer studies in several mammalian species have demonstrated a similar musculotopic organization of the hypoglossal motoneurons which innervate individual tongue muscles. The distribution of this musculotopic organization in nonmammalian tetrapods, however, has not received detailed investigation. As part of an ongoing study on the comparative organization of the vertebrate hypoglossal nucleus, the musculotopic organization of the hypoglossal nucleus of Rana pipiens was studied by injection of lectin-conjugated horseradish peroxidase into four distinct tongue muscles and the geniohyoid muscle. Injections into the hyoglossus muscle label neurons in dorsal regions of the hypoglossal nucleus in middle and rostral nucleus levels. Injections into the genioglossus basalis muscle label neurons in ventral and lateral regions of the hypoglossal nucleus in caudal nucleus levels. Injections into the genioglossus medialis muscle label neurons in dorsal regions in caudal levels, throughout the nucleus in middle levels, and in ventral regions in more rostral levels. Injections into the geniohyoid muscle label neurons in the ventral tip of the hypoglossal nucleus and in the ventromedial corner of the medullary gray matter in middle and rostral nucleus levels. These results demonstrate that the organization of the hypoglossal nucleus in Rana pipiens is more complex than previous tracer studies indicated. Similarities in the musculotopic organization of the amphibian and mammalian hypoglossal nuclei suggest an evolutionary conservatism of the motor system controlling tongue movement. PMID- 1865015 TI - Reinnervation of cerebellar Purkinje cells by climbing fibres surviving a subtotal lesion of the inferior olive in the adult rat. I. Development of new collateral branches and terminal plexuses. AB - Cerebellar climbing fibres react by collateral sprouting after subtotal lesions of the inferior olive, and the newly formed branches are able to reinnervate neighbouring denervated Purkinje cells. In the present paper, we used the Phaseolus vulgaris leucoagglutinin (PHA-L) tracing technique to label the climbing fibres and study their plasticity in detail at the light microscopical level. The specific objectives were to study the time course and morphological aspects of their sprouting, to estimate their extent of growth, and to compare the newly formed terminal plexuses with normal climbing fibres. Intraperitoneal injection of 3-acetylpyridine induced degeneration of the majority of the olivary neurones, which terminate as climbing fibres in the cerebellar cortex. Regularly, small numbers of neurones survived in the inferior olive. In the cerebellar cortex scattered surviving climbing fibres were found, which were devoid of any sign of injury. Already 3 days after the lesion, surviving climbing fibres had emitted collateral branches, which elongated for some distance through the molecular layer and ended with a number of varicosities and very fine branchlets. By 7 days, it was possible to recognize new developing arbours which grew in the molecular layer with the same orientation as normal climbing fibres. At longer survival times, extensive terminal arbours had developed and double labelling experiments confirmed that they terminated around the proximal dendrites of Purkinje cells. The newly formed terminal plexuses resembled, in all essential aspects, normal climbing fibres. In addition, from 1 month onward, it was evident that every surviving climbing fibre was able to form several new terminal plexuses reinnervating a number of neighbouring Purkinje cells. The result of this process was the formation of large clusters of newly formed plexuses around the parental arborization. Quantitative estimates indicated that the domain of innervation of single surviving climbing fibres could be increased by more than six times. It is concluded that climbing fibres surviving a subtotal olivary lesion are capable of extensive sprouting, axonal growth, and formation of new terminal plexuses, which resemble normal climbing fibres. Previous electrophysiological evidence indicates that this reinnervation is functional. The high specificity with which sprouting olivary axons reinnervate the proximal Purkinje cell dendrites suggests the existence of precise interactions between the growing fibres and their target. This example of "homotypic" collateral sprouting and reinnervation may thus provide a useful model for the study of nerve-target interactions. PMID- 1865016 TI - Reinnervation of cerebellar Purkinje cells by climbing fibres surviving a subtotal lesion of the inferior olive in the adult rat. II. Synaptic organization on reinnervated Purkinje cells. AB - A salient feature of the cerebellar Purkinje cells is the highly ordered distribution of their excitatory afferents on the dendritic tree. Climbing fibres synapse exclusively on the proximal dendrites, whereas parallel fibres articulate with the distal branches, the so-called spiny branchlets. This input organization is lost following the removal of climbing fibres. Such denervation results in the formation of a large number of new spines on the proximal dendrites, and these become contacted by sprouting parallel fibres, which thereby extend their domain of innervation. We have previously shown that the climbing fibres surviving a subtotal lesion of the inferior olive sprout and reinnervate neighbouring Purkinje cells. In the present ultrastructural study, we have investigated the features of Purkinje cells reinnervated by sprouting climbing fibres. The objectives were to examine the fine morphology of the newly formed synapses and to determine whether the modifications of Purkinje cell morphology and afferent organization are reversed by this reinnervation. Surviving climbing fibres were labelled by the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) and immunohistochemically visualized by means of the gold-substituted silver peroxidase technique, 2 and 6 months after 3-acetylpyridine lesions of the inferior olive in adult rats. Sprouting climbing fibres and newly formed arborizations were identified in the light microscope, isolated, and cut in serial ultrathin sections for electron microscopic analysis. The labelled boutons belonging to newly formed terminal plexuses exhibited the typical morphological features of climbing fibre terminals, i.e., a high number of round synaptic vesicles and a few small mitochondria. Most frequently they formed asymmetric synapses on stubby thorns protruding from the proximal Purkinje cell dendrites. In some instances, however, the postsynaptic element consisted of long slender spines or spines showing an atypical morphology. A number of labelled boutons was also in contact with the perikarya of reinnervated Purkinje cells, either articulating with spines or synapsing directly on the smooth somatic surface. The proximal dendrites of denervated Purkinje cells were characterized by large numbers of spines, which were frequently postsynaptic to parallel fibres. By contrast, Purkinje cells reinnervated by the sprouting climbing fibres generally showed a lower number of spines on their proximal dendrites, indicating a reversal of this morphological change. The aberrant parallel fibre input was also decreased on reinnervated dendrites or had completely disappeared. Nevertheless, some reinnervated Purkinje cells showed the persistence of some parallel fibre synapses on their proximal dendrites. On occasion, climbing fibre and parallel fibre boutons synapsed on the same spine. PMID- 1865017 TI - Inhibition of axonal development after injection of neurofilament antibodies into a Xenopus laevis embryo. AB - The ability to target specific cytoskeletal components in axons for disruption within intact developing embryos would provide a valuable tool for studying neuronal development. Neurofilaments are an attractive target for such an approach, because they are neuron specific and are expressed late in embryogenesis principally beginning during axon outgrowth. No pharmacological agents are currently available that disrupt neurofilaments without also affecting general development. One approach that has been used successfully to affect proteins in vivo is to inject specific antibodies into living cells. We employed this approach in Xenopus laevis embryos by injecting two antibodies directed against the middle molecular weight neurofilament protein (NF-M) into a single blastomere of a two-cell stage embryo. Injected antibodies could be detected for as long as 3.5 days in cells descended from the injected blastomere. Only cell bodies of neurons descended from anti-NF-M-injected blastomeres contained abnormal accumulations of intermediate filament proteins, and peripheral nerve development was unilaterally retarded in these neurofilament antibody-injected tadpoles. Such accumulations and peripheral nerve defects were not seen in neurons derived from uninjected blastomeres or from blastomeres injected with control antibodies. These data demonstrate the usefulness of specific antibodies to perturb neuronal development in intact frog embryos and, in addition, suggest a role for neurofilaments in axon elongation. PMID- 1865018 TI - Comparative aspects of the basal ganglia-tectal pathways in reptiles. AB - To determine how the basal ganglia in reptiles may influence visuomotor behavior, the connections from the basal ganglia to the tectum of the midbrain were studied in several species of reptiles. Immunohistochemical studies by means of antibodies against Leu-enkephalin (LENK) as well as experimental hodological studies with anterograde (PHA-L) and retrograde (HRP, Fluorogold, Cholera toxin) tracers were carried out. The results indicate that within the class of Reptilia, two different patterns occur: one in which information from the basal ganglia is relayed to the tectum via the substantia nigra as well as via a pretectal, enkephalinergic cell group, and another one in which only the ventral route, via the substantia nigra, is present. The former pattern is found in turtles, crocodiles, and the lacertid lizards Podarcis and Gallotia, and the latter pattern in the gekkonid lizards Gekko and Eublepharis, in Varanus, and in the snakes Python and Thamnophis. The presence or absence of the pretectal relay center is reflected in the laminar distribution of LENK immunoreactivity in the tectum. The apparent lack of a pretectal relay in nocturnal gekkonids and in snakes underlines the hypothesis (Reiner et al., '84: T.I.N.S. 7:320-325) that a de-emphasis of visual-basal ganglia mechanisms has occurred during the evolution of ancestral reptiles to modern mammals. PMID- 1865020 TI - Blood-nerve barrier in the frog during wallerian degeneration: are axons necessary for maintenance of barrier function? AB - Blood-nerve barrier tissues (endoneurial blood vessels and perineurium) of the frog's sciatic nerve were studied during chronic Wallerian degeneration to determine whether barrier function depends on the presence of intact axons. Sciatic nerves of adult frogs were transected in the abdominal cavity; the ends were tied to prevent regeneration and the distal nerve stumps were examined. Vascular permeabilities to horseradish peroxidase and to [14C]sucrose increased to day 14, returned toward normal levels by 6 weeks, and continued at near normal levels to 9 months. Perineurial permeabilities to the tracers increased by day 10 and remained elevated at 9 months. Proliferation of perineurial, endothelial, and mast cells occurred between 3 days and 6 weeks, resulting in an increased vascular space (measured with [3H]dextran) and number of vascular profiles. The perineurium increased in thickness and the mast cells increased in number. This study indicates that during Wallerian degeneration of the frog's sciatic nerve there is 1) a transitory increase in vascular permeability distal to the lesion, that is related to changes within the endoneurium; 2) an irreversible increase in permeability of the perineurium, which begins later than that seen in the endoneurial blood vessels; and 3) proliferation of non-neuronal components in the absence of regenerating neuronal elements. The results indicate that maintenance of vascular integrity does not require the presence of axons in the frog's peripheral nerve, whereas perineurial integrity and barrier function are affected irreversibly by Wallerian degeneration. PMID- 1865019 TI - Cerebellar Purkinje cell markers are expressed in retinal bipolar neurons. AB - Previous studies have been directed at the elucidation of neuron-specific gene expression in the mammalian central nervous system. In particular, we have identified a series of marker molecules that are expressed in cerebellar Purkinje cells with varying degrees of specificity. Here, we show by light microscopic immunocytochemistry and Northern transfer and hybridization that two of these markers, namely, L7 and PEP19, are expressed in the retina of mouse and rabbit, while a third marker, cerebellin, is absent. Light and electron microscopic immunocytochemistry proves that L7-like immunoreactivity is restricted to rod bipolar cells, while PEP 19-like immunoreactivity is distributed in both rod and cone bipolars. PEP19 is also expressed by subsets of amacrine and ganglion cells. The density of PEP19-positive bipolar cells is greater than that of L7-positive bipolar cells, although the density of each is approximately equal in central and peripheral portions of the retina. An antiserum to a fourth Purkinje cell marker, vitamin D-dependent calcium-binding protein-28 kD (CaBP), reveals primarily axonless horizontal cells, but also subsets of rod bipolar, amacrine, and, in the mouse but not in the rabbit, ganglion cells. The processes of immunoreactive cell bodies form discrete bands in the internal plexiform layer, and mixtures of the antisera help distinguish their identity. Thus, these Purkinje cell markers can be used at the electron microscopic level to unravel the extremely complex neuropil of this retinal layer. Furthermore, knowledge of the retinal distribution of this panel of molecules is of general value for future studies of retinal neuronal typology and can serve to map the densities of subsets of bipolar cells throughout the retina. The expression of L7 and PEP19 in bipolar cells and in Purkinje cells suggests a biochemical relationship between these two spatially distant neuronal populations. PMID- 1865021 TI - Topographic organization of cortical input to striate cortex in the Cebus monkey: a fluorescent tracer study. AB - Cortical afferents to area V1 were studied in seven Cebus monkeys by means of retrograde fluorescent tracers. Injections were placed in V1, under electrophysiological guidance, in the regions of representation of both the upper and lower visual quadrants, at eccentricities that ranged from 0.5 to 64 degrees. In all cases retrogradely filled neurons were found in retinotopically corresponding portions of areas V2 and MT, as defined electrophysiologically (Rosa et al: J. Comp. Neurol. 275:326, 1988; Fiorani et al: J Comp Neurol 287:98, 1989). The results also revealed two other visual zones located anterior to V2 here named third and fourth visual areas. A topographical organization of the connections was observed in these areas, with upper quadrant located ventrally and lower quadrant located dorsally. A clear central-peripheral gradient, from the lateral to the medial cortical surface, was also observed in these areas. Lower field injections revealed crude topographic organization in area DZ and a diffuse projecting zone in the annectent gyrus. Peripheral injections in V1 revealed a clear upper and lower field segregation in areas PO and prostriata as well as a complex topography in MST. In addition, another region of labeling revealed the presence of an area, the temporal ventral posterior region, with an organized topographic representation of the upper field, with a central to peripheral gradient, from the lateral to the medial cortical surface. Three groups of cortical areas were distinguished according to the laminar distribution of neurons labeled from V1. In the first group, which is characterized by dense infra- and supragranular labeling, only V2 was included. The second group consists of areas V3, MT, and PO. These areas show dense labeling in the infragranular layers and occasionally sparse labeling in the supragranular layers. Finally, V4 and the other projecting areas, which are characterized by exclusive labeling of the infragranular layers were included in the third group. PMID- 1865022 TI - The effect of heparin on glomerular coagulation induced in mice by cycloheximide and bacterial lipopolysaccharide. AB - The glomerular capillary coagulation in mice which follows challenge with cycloheximide and a submicrogram dose of endotoxin was shown to become fully established between 4 h and 6 h after challenge. Complete protection against the renal lesion was achieved by heparin treatment 4 h after challenge. The antifibrinolytic agent, tranexamic acid, given 4 h and 6 h after challenge, abolished this heparin-induced protection, but had no effect when given 6 h and 8 h after challenge. These findings suggest that heparin in some way delayed the onset of cycloheximide and endotoxin-induced irreversible coagulation in glomerular capillaries, and by so doing, allowed the development of local, protective, fibrinolytic activity. A relatively brief period of such fibrinolytic activity appeared to confer lasting protection against coagulation in glomerular capillaries. Appropriately timed treatment with hydrocortisone also abolished the heparin-initiated protection, and the evidence suggests that the steroid acts by inhibiting the development of local fibrinolytic activity. PMID- 1865023 TI - Experimental haemarthrosis in rhesus monkeys: morphometric, biochemical and metabolic analyses. AB - The effects of a single episode of massive haemarthrosis in rhesus monkeys were studied. Autologous whole blood was injected into a femorotibial joint of 16 anaesthetized monkeys, equally divided into four groups and killed 7 days, 2, 3 and 6 months post-injection (PI). Synovial membrane and femoral articular cartilage were analysed morphometrically and articular cartilage was further analysed biochemically and metabolically. At 7 days PI, morphometric evaluation revealed a significant increase (P less than 0.05) in synovial membrane cellularity and synovial intimal thickness of injected joints versus control joints. This change was no longer evident 2 months PI. There was also an overall (n = 16) significant increase (P less than 0.05) in femoral articular cartilage cellularity in injected joints. The average chondrocyte lacuna area of injected joints was not statistically different from the control joints. Biochemical analyses of femoral articular cartilage revealed a significant decrease in hexosamine concentration (P less than 0.05) of injected joints. There was no significant difference between the injected and control joints in hydroxyproline or total protein concentration. Metabolic analyses revealed a significant increase (P less than 0.05) in cartilage collagenous protein production by injected joints compared with control joints. There were no significant differences in cartilage or secreted total protein production between injected and control joints. There were also no significant differences in cartilage or secreted proteoglycan production between joints. Morphometric evaluation of articular tissues following massive haemarthrosis has quantified a temporary hyperplastic reaction. A significant decrease in cartilage hexosamine concentration in haemarthrotic joints suggests this is a crucial biochemical event in the pathogenesis of blood-induced cartilage destruction. PMID- 1865024 TI - Lectin histochemistry of feline polyglucosan bodies. AB - Lectin histochemistry was conducted to identify sugar residues of the polyglucosan bodies (PGB) in the feline brain. PGB stained with Concanavalia ensiformis agglutinin (Con A) and peanut agglutinin, but not with soybean agglutinin, wheat germ agglutinin, Dolichos biflorus agglutinin, Ricinus communis agglutinin or Ulex europaeus agglutinin. In addition, PGB bound to Con A after periodate oxidation. These results suggest that feline PGB contain mannose and galactose in addition to glucose and that the partial component of PGB is derived from rough endoplasmic reticulum and the Golgi apparatus. PMID- 1865025 TI - Granulomatous inflammation and monstrous giant cells in response to intraperitoneal hormone implants in channel catfish (Ictalurus punctatus). AB - Plastic implants (2.7 mm maximum dimension) of an ethyl vinyl acetate copolymer (EVAc) matrix, containing inulin, bovine serum albumin (BSA) and luteinizing hormone releasing hormone (LHRH), were covered with impervious EVAc and then surgically placed into the peritoneal cavity of 1-year-old channel catfish, Ictalurus punctatus. In fish kept in cold water (13 degrees C), 10 per cent of the implants per month were encapsulated by granulation tissue. In fish kept in warm water (27 degrees C), 20 per cent of the implants per month were encapsulated, with a total of 86 per cent encapsulated at 5 months. In addition to fibroblasts and capillaries, the granulation tissue included macrophages, neutrophils, lymphocytes, plasma cells, multinucleated giant cells and a matrix of collagen fibres. The density of the fibrous capsule increased with time. In a separate investigation, it was found that the thickness of the capsule was directly proportional to the degree of exposure of the EVAc matrix to the fish (exposure influenced by the rate of dissolution of the capsule content). Monstrous giant cells with up to 600 nuclei per 5 microns thick section were seen in capsules around implants. On intraperitoneally implanted cover glasses, whole giant cells contained up to 6000 nuclei and were interconnected by cytoplasmic bridges. Signs of neoplasia, implant expulsion or massive adhesions were not seen. PMID- 1865026 TI - Equine cutaneous mastocytoma: morphology, biological behaviour and evolution of the lesion. AB - Thirty equine cutaneous mastocytomas were examined histologically and two were studied ultrastructurally. Lesions were characterized by distinct sheets of well differentiated mast cells with variable degrees of eosinophil infiltration, collagen degeneration, necrosis, granulomatous inflammation and fibrosis. Twenty two of 25 growths did not recur for up to 6 years after surgical excision, two recurred at the surgical site and one spontaneously regressed less than 3 months after obtaining a biopsy sample. Equine cutaneous mastocytoma is a benign proliferative lesion which seldom recurs after excision. The varied histological presentation of equine mastocytoma can be attributed to a sequence of events initiated by a cutaneous mast cell proliferation. It is suggested that these mast cells release chemotactic factors for eosinophils which accumulate and degranulate, initiating collagen degeneration and cellular necrosis with subsequent granulomatous inflammation and fibrosis. The focal spontaneous nature of the primary mast cell proliferation is typical of neoplasia. PMID- 1865027 TI - Haematological and pathological responses to experimental Trixacarus caviae infection in guinea pigs. AB - Outbred guinea pigs became infected with the mite Trixacarus caviae (Acarina, Sarcoptidae) when introduced into an infected colony. Mite numbers were highest after one month, then fell progressively. Infected guinea pigs developed a neutrophilia, monocytosis, eosinophilia and basophilia. Despite pronounced reactive changes in the superficial lymph nodes, infected guinea pigs developed only a mild dermatitis. In contrast, home bred animals, susceptible to T. caviae acquired many mites and developed a severe chronic dermatitis. Trixacaral manage in guinea pigs offers considerable potential for the study of mite infections in man and animals. PMID- 1865028 TI - Spontaneous ovarian tumour in a medaka (Oryzias latipes). AB - Swelling of the abdomen was found in an adult female medaka (Oryzias latipes). Multiple tumour masses occupying most of the abdominal cavity were found at necropsy. Histologically, the tumour consisted of homogeneous round cells arranged in islands and occasional trabecular structures with thin capsules. Ova at various stages of maturation were seen in the periphery of the tumour mass. Metastasis was observed in the vicinity of the thyroid gland with accompanying infiltration by lymphocytic cells and also abdominal muscles. The tumour cells were characterized by a large ovoid nucleus with no aggregation of heterochromatin, occasional mitotic figures and prominent nucleoli. Examination by electron microscopy showed cells with scant cytoplasm but many ribosomes and a few other organelles. Annulate lamellae and dense cytoplasmic masses were also frequently observed. Based on the above features, the tumour was diagnosed as an ovarian dysgerminoma, the first reported case in a medaka. PMID- 1865029 TI - An immunohistochemical study of spontaneous lymphomas in the C57B1/10J mouse. AB - Immunocytochemistry was used to examine 26 cases of composite lymphoma in the mouse mesenteric lymph node. The diagnosis was made by light microscopic criteria. A selection of polyclonal antibodies to light (Kappa and Lambda) and heavy chain (IgD, IgM, IgC, IgA, IgE) antigens was used together with three monoclonal antibodies to T cells, B cells (HLA-DR) and macrophages. Twenty lymphomas were classified as B cell and six as T cell. The B cells were subdivided into IgM and IgD (five), IgD (five), IgM (three) and IgA (one), three undifferentiated and, in three, there was insufficient tissue for further typing. There did not appear to be any correlation between the morphological appearance and the immunophenotype. PMID- 1865030 TI - Hepatic mitochondrial redox state in hypotensive brain-dead patients and an effect of dopamine administration. AB - Arterial blood ketone body ratio, reflecting hepatic mitochondrial redox state, was measured in 26 brain-dead patients who were hypotensive but hemodynamically stable. All of them had substantially normal hepatic function. In 18 of the patients, blood ketone body ratio was maintained within the normal range in spite of hypotension. This was in marked contrast to the markedly decreased blood ketone body ratio often observed in patients in shock. This phenomenon was especially conspicuous in those who had not received exogenous dopamine infusion. It is suggested that hepatic mitochondrial redox state can probably be maintained despite systemic hypotension in brain-dead patients. Dopamine administration, on the other hand, is suggested to be a contributing factor to the reduction of hepatic mitochondrial redox state in hypotensive brain-dead patients. This study may provide a guideline for effective preservation of hepatic function in the body of brain-dead patients. PMID- 1865031 TI - Improved determination of static compliance by automated single volume steps in ventilated patients. AB - A new method for determination the static compliance of the respiratory system is described ("static compliance by automated single steps"--SCASS). In 12 ventilated patients pressure/volume (P/V) curves were determined by automated repetitive occlusion (6 s) at single volume steps and compared to the conventional syringe method (SM). All measurements were corrected for effects of temperature, humidity and pressure (THP). SM was found to be significantly influenced by intrapulmonary gas exchange causing an effective mean volume deficit of 217.4 +/- 65.7 ml (BTPS) at the end of the deflation. In contrast to that, the short duration of occlusion in SCASS minimize the gas exchange effects. The methodical differences between both methods result in overestimation of the inflation compliance in the uncorrected SM (SMuncorr: 83.4 +/- 12.6; SCASS: 76.0 +/- 11.9 ml/cmH2O. p less than 0.01) and underestimation of the deflation compliance resp. (SMuncorr: 58.3 +/- 7.5; SCASS: 79.1 +/- 15.0 ml/cmH2O. p less than 0.005). In contrast to the P/V curves by SM no significant hysteresis was found by SCASS. Gas exchange seems to be the main reason for the hysteresis. Even after correcting gas exchange and THP effects a significant hysteresis remained. The SCASS method avoids these problems and allows furthermore an accurate checking of leaks. PMID- 1865032 TI - Acute pulmonary emboli associated with guidewire change of a central venous catheter. AB - The potential complications of percutaneous venous catheterizations are many and include pneumothorax, subclavian and carotid artery puncture, hematoma, air embolism, catheter malposition, catheter fragment embolization, venous thrombosis and infection. This case report describes a patient who developed angiographically documented pulmonary emboli associated with the changing of a central venous catheter over a guidewire using Seldinger technique. This episode adds the possibility of acute pulmonary emboli to the list of potential complications from central venous catheterizations. PMID- 1865033 TI - Wegener's granulomatosis presenting as diffuse pulmonary hemorrhage. AB - A 35-year-old woman experienced diffuse intraalveolar haemorrhage with respiratory distress and acute renal failure. Renal histology and evolution confirmed Wegener's granulomatosis. Early use of immunosuppressive drugs allowed weaning from mechanical ventilation and temporary improvement of the renal failure. A review of the literature emphasizes the rarity of alveolar hemorrhage as an initial symptom of Wegener's granulomatosis and the necessity of aggressive management. PMID- 1865034 TI - Transient unilateral hyperlucent lung due to mucus plugs. AB - A 63-year-old patient with a tracheostomy presented with a transient unilateral hyperlucent lung and absent breath sounds over the left lower lobe. A tracheobronchial cast and an additional floating mucus plug in the left lower lobe bronchus were retrieved with fiberbronchoscopy. Subsequently normalisation of ventilation and radiological appearance of the left lung occurred. PMID- 1865035 TI - Acyclovir clearance by CAVHD. PMID- 1865036 TI - Nosocomial maxillary sinusitis during mechanical ventilation: comparison of orotracheal versus the nasotracheal route for intubation. PMID- 1865037 TI - Management of resources in intensive care. PMID- 1865038 TI - A nordic ECMO saga or whither ECMO? PMID- 1865039 TI - Assessing tissue perfusion. PMID- 1865040 TI - Total extracorporeal lung assist--a new clinical approach. AB - Total extracorporeal lung assist (ECLA) requires a bypass flow approaching cardiac output. Recirculation of venous blood through the oxygenator is minimized with a veno-right ventricular cannulation technique which separates venous drainage from returned oxygenated blood. A case of posttraumatic ARDS was treated with surface-heparinized veno-right ventricular ECLA for 35 days. Cardiac output was stabilized by means of sedation, hypothermia (35 degrees C) and beta blockers (pulse rate less than 90) in order to match the maximal venous drainage achieved (5.5 l/min). A bypass flow around 85% of cardiac output resulted in mean arterial PO2 values between 9-13.6 kPa without any contribution from the lungs. Low platelet counts and a marked bleeding tendency complicated treatment, even though no heparin was used during the last 24 days of ECLA. Weaning from the ventilator was accomplished 2 months after ECLA. Lung function tests show constant improvement. PMID- 1865041 TI - Assessment of the perfusion in peripheral tissue beds by subcutaneous oximetry and gastric intramucosal pH-metry in elective colorectal surgery. AB - Gastric intramucosal pH (pHi) and subcutaneous oxygen tension (PscO2) were compared with traditional perfusion parameters in patients undergoing elective colorectal surgery and were related to clinical outcome. Ten patients were studied per- and postoperatively and tissue oximetry studies were also performed in a group of 10 healthy volunteers. The response of PSCO2 to oxygen breathing proved to be the most sensitive predictor of clinical outcome. Of the 10 patients 8 failed to respond to an O2 challenge, while all 10 volunteers in the control group did so. Out of those 8 patients 6 presented with mainly infectious complications while only 3 had an inadequate perioperative urine output and none presented with signs of arterial or of gastric intramural acidosis. The present study suggests a possible relationship between clinical outcome and oxymetric signs of tissue hypoperfusion after O2 challenge in surgical patients, even in the presence of an adequate urine output and a normal gastric wall pH. PMID- 1865042 TI - Continuous multivariable monitoring in neurological intensive care patients- preliminary reports on four cases. AB - Evoked potential monitoring is a standard examination method in neurological intensive therapy units. Previously, multimodality observation was only possible in follow-up examinations. First experience with a new bed-side system continuously monitoring 12 neurophysiological and clinical parameters is reported. It consists of a personal computer and various stimulation units. EEG activity, median nerve somatosensory evoked potentials (SEPs) and brainstem auditory evoked potential (BAEPs) are recorded. Additionally, EEG spectral band power, heart rate, heart rate variability, intracranial pressure, body temperature, expiratory PCO2, blood pressure and transcutaneously measured oxygenation can be monitored. This paper reports on 4 exemplary cases of the 33 patients we have monitored to date, illustrating the principles and main advantages of the system. The system was developed to support the observation of ICU patients as well as to aid therapeutic decisions. It supports the clinical determination of brain death by specifying the deterioration of various neurological systems. PMID- 1865043 TI - Evoked potentials in severe herpes simplex encephalitis. AB - Diagnostic and prognostic value of evoked potentials (EP) were studied in 5 patients with severe herpes simplex encephalitis (HSE). Latency of the third negative cortical N70 peak, elicited by median nerve stimulation, was prolonged in 3 survivors with Glasgow coma score of less than or equal to 6 (115 vs 71 ms in controls, p less than 0.05), but normal after improvement of the acute disease. N70 right to left interhemisphere difference was increased initially in the 4 survivors (26 vs 3 ms in controls, p less than 0.05) indicating focal brain involvement, a crucial finding in HSE. The first cortical N20 peak was preserved in all survivors even during deep coma where evaluation of brain function is difficult. Auditory brainstem EP were normal in all patients and useful to exclude brainstem death. In severe HSE, somatosensory long-latency EP are an effective monitor of the level of impaired consciousness and can detect brain focal signs. Short-latency N20 components may be predictive of the outcome. PMID- 1865044 TI - Hyperactivity and the fragile X syndrome. AB - Workers who have claimed an association between Fragile X [fra(x)] Syndrome and Hyperactivity and aggressive behavior have done so despite the lack of controlled studies using standard diagnostic criteria. Accordingly, we provided a controlled test of the hypothesis that individuals with the fra(x) Syndrome are more hyperactive and have more symptoms of aggression than other mentally retarded individuals. The test formed part of a study to assess autistic behavior in fra(x) individuals. A sample of fra(x) individuals was obtained from the register of a clinical genetics unit and individually matched for age, sex, and IQ with mentally retarded individuals selected from assessment centres. Forty-five pairs of fra(x) cases and control individuals were compared on criteria which reflected DSM-III concepts of hyperactivity and on criteria reflecting aggressive behavior. The comparison failed to find a higher prevalence of these symptoms in the fra(x) group. An analysis of the study's statistical power suggested that it is unlikely that the investigation failed to detect a large to medium difference between fra(x) individuals and control individuals in the symptoms investigated. PMID- 1865045 TI - Methylphenidate speeds evaluation processes of attention deficit disorder adolescents during a continuous performance test. AB - Forty-six Attention Deficit Disorder (ADD) adolescents took a Continuous Performance Test (CPT) under placebo and methylphenidate (35.33 mg/day). The task required pressing one button for targets (p = .133), and another button for nontargets. Subjects displayed a strong bias to make the more frequent negative response before completely evaluating stimuli. Consistent with this assumption, subjects responded faster (by an average of 87 ms) to nontargets than to targets. Methylphenidate increased accuracy and speeded reaction times (RTs) to targets. The drug also increased the amplitude of the P3b component of the event-related potential for nontargets and shortened the latency of P3b for both targets and nontargets. These results suggest increased capacity allocation to and faster evaluation of task stimuli. Finally, the stimulant lengthened relative motor processing time (RT-P3b latency) for nontargets, a finding implying that response processing was accomplished with the benefit of earlier completion of evaluation processes for these stimuli. PMID- 1865046 TI - Disruptive boys with stable and unstable high fighting behavior patterns during junior elementary school. AB - Boys' fighting was assessed at ages six, eight, and nine. The boys (N = 69) had been selected from the 30% most disruptive children in kindergartens from low socioeconomic neighborhoods. Twenty-three percent of these disruptive boys were rated as high fighters on three assessments ("stable high fighters"), and 28% were rated as high fighters on two of the three assessments ("variable high fighters"). Forty-two percent were rated as high fighters only one out of three assessments ("occasional high fighters") and 7% were never rated as high fighters. Only high fighting in two successive years significantly increased the risk of being rated a high fighter in a following year. At age 10, stable high fighters (high fighters at ages 6, 8, 9) were perceived by teachers, peers, mothers, and the boys themselves as more disruptive and more antisocial than occasional high fighters. These results show an impressive self-other agreement in boys who have adopted a physically aggressive life style from an early age. The three groups did not differ on individual family demographic characteristics, but stable high fighters had a higher mean on an index of family socioeconomic disadvantage. Results indicate that the aggression scales which include only a few physical aggression items and many disruptive items (oppositional behavior, rejection, hyperactivity, inattention, etc.) probably aggregate two kinds of disruptive boys, the high-frequency fighters at high risk for stable disruptive, physically aggressive, and antisocial behaviors, and the disruptive low-frequency fighters who are at a lower risk of stable disruptive behavior and at a lower risk of early antisocial behavior. PMID- 1865047 TI - Hard-to-manage preschool boys: family context and the stability of externalizing behavior. AB - Preschool boys identified by their teachers as active, inattentive, and impulsive (N = 42) were compared with matched classroom controls (N = 43) and with parent identified problem boys (N = 27) on measures of family functioning often associated with children's problem behaviors, including family history of psychopathology, stressful life events, and family composition. Teacher identified and parent-identified problem boys did not differ on measures of family adversity, and both groups came from less well functioning families than comparison boys. Mothers of problem boys, regardless of referral source, were more negative and controlling toward their sons when observed in a compliance task. Children's problem behaviors were moderately stable over a one-year follow up period; initial symptom levels, maternal self-reported depression, and negative maternal control predicted follow-up ratings of externalizing problems. PMID- 1865048 TI - A qualitative and serial analysis of social problem solving in aggressive boys. AB - Social problem solving skills in 84 elementary school aged boys were assessed to identify those responses most salient in the prediction of ratings of aggressive and socially withdrawn behavior. Aggressive and socially withdrawn boys did not differ from the control group in the number of effective first solutions generated to the hypothetical stories. The control group generated significantly more effective solutions as second alternatives to the stories than did the aggressive or socially withdrawn boys. In addition, the number of effective second responses generated significantly predicted both aggression and social withdrawal after controlling for verbal problem solving. Results are discussed in terms of differences in cognitive processes as well as implications for treatment. PMID- 1865049 TI - Linking family characteristics with poor peer relations: the mediating role of conduct problems. AB - Parent, teacher, and peer ratings were collected for 75 grade school boys to test the hypothesis that certain family interaction patterns would be associated with poor peer relations. Path analyses provided support for a mediational model, in which punitive and ineffective discipline was related to child conduct problems in home and school settings which, in turn, predicted poor peer relations. Further analyses suggested that distinct subgroups of boys could be identified who exhibited conduct problems at home only, at school only, in both settings, or in neither setting. Boys who exhibited cross-situational conduct problems were more likely to experience multiple concurrent problems (e.g., in both home and school settings) and were more likely than any other group to experience poor peer relations. However, only about one-third of the boys with poor peer relations in this sample exhibited problem profiles consistent with the proposed model (e.g., experienced high rates of punitive/ineffective home discipline and exhibited conduct problems in home and school settings), suggesting that the proposed model reflects one common (but not exclusive) pathway to poor peer relations. PMID- 1865050 TI - Development and functional significance of private speech among attention-deficit hyperactivity disordered and normal boys. AB - We compared the development of spontaneous private speech and its relationship to self-controlled behavior in a sample of 6- to 12-year-olds with attention-deficit hyperactivity disorder (ADHD) and matched normal controls. Thirty-eight boys were observed in their classrooms while engaged in math seatwork. Results revealed that ADHD children were delayed in private speech development in that they engaged in more externalized, self-fuiding and less inaudible, internalized speech than normal youngsters. Several findings suggest that the developmental lag was a consequence of a highly unmanageable attentional system that prevents ADHD children's private speech from gaining efficient mastery over behavior. First, self-guiding speech was associated with greater attentional focus only among the least distractible ADHD boys. Second, the most mature, internalized speech forms were correlated with self-stimulating behavior for ADHD subjects but not for controls. Third, observations of ADHD children both on and off stimulant medication indicated that reducing their symptoms substantially increased the maturity of private speech and its association with motor quiescence and attention to task. Results suggest that the Vygotskian hypothesis of a unidirectional path of influence from private speech to self-controlled behavior should be expanded into a bidirectional model. These findings may also shed light on why treatment programs that train children with attentional deficits in speech to-self have shown limited efficacy. PMID- 1865051 TI - Application of adsorption kinetics for estimation of dissociation constants. AB - Substances such as drugs, as well as special ligands with expressive biospecific properties, all with different affinities, interact with proteins which can be characterized by dissociation constants. The method for estimation of the dissociation constant on the basis of adsorption kinetics was verified for two typical cases: adsorption of lactate dehydrogenase onto bead cellulose derivatized by reactive dyes C.I.2. or C.I.19, and adsorption of different drugs (neuroleptics and local anesthetics) onto calmodulin immobilized on agarose gel. The real equilibrium values obtained by using the complete time-concentration model of adsorption were fitted according to the respective adsorption isotherms by non-linear regression. PMID- 1865052 TI - Cleavage by protease from Staphylococcus aureus V8: an improvement in the sequence analysis of human hemoglobin variants. AB - Protease from Staphylococcus aureus V8 cleaves either at glutamic residues or at both aspartic and glutamic residues, depending on the experimental conditions. In structural analyses of human hemoglobin variants, the specificity of this enzyme is of considerable interest to localize substitutions occurring in medium or large size peptides as it cleaves in smaller fragments which may be unambiguously characterized. It may also recognize the replacement of an acidic residue by the corresponding amide, or vice versa, avoiding protein sequence analysis. The various aspects of the use of protease V8 are illustrated by the study of four alpha chain hemoglobin variants concerning peptides alpha T-9 and alpha T-12b. PMID- 1865053 TI - Electroporation of lymphoid cells: factors affecting the efficiency of transfection. AB - We have increased the efficiency of electroporation of lymphoid cells over fifty fold by optimising several biological and electrical parameters. Under optimised conditions, the electroporation efficiency was comparable to that reported for other cell types. Actively dividing cells were crucial for high transient transfection signal. The two most important electrical parameters were high capacitance (960 microF) and moderate decay constants in the range of 10-15 ms. The optimal field strength depended on the cell line, but was in the range 0.6-1 kV/cm. Administering the pulse in medium lacking serum gave higher efficiency than when isotonic salt solution was used and the transfection signal was depressed if cells and DNA were allowed to incubate for several minutes either before or after the pulse. Electroporation was carried out at room temperature and there was no advantage in using low temperatures (0-4 degrees C). When electroporated cells were grown in conditioned medium, the signal was enhanced about two fold depending on the source of the conditioned medium. PMID- 1865054 TI - Differential precipitation and zinc chelate chromatography purification of biologically active HTLV-I Tax1 expressed in E. coli. AB - A protocol which involves sequential ammonium sulfate precipitation and zinc chelate chromatography to purify the HTLV-I Tax1 protein expressed in E. coli is described. The final Tax1 product is greater than 90% pure and the yield is approximately 1 mg per liter of liquid culture. The purified Tax1 protein is biologically active in indirect in vitro DNA binding assays and cellular NF-kB induction experiments. PMID- 1865055 TI - Microinjection into Xenopus oocytes: a precise semi-automatic instrument and optimal parameters for injection of mRNAs. AB - A new apparatus for the injection of Xenopus oocytes is described which provides semi-automatic cell handling together with highly accurate and reproducible volume delivery. Using the system requires very little skill, yet it gives 6.3% average reproducibility in the 5 to 70 nl volume range. The instrument uses a fixed injector system driven by an Inchworm piezoelectric positioner or, in a low cost version, by a Rainin EDP-2 battery-operated motorized pipette. A movable, vacuum-operated oocyte holder minimizes lateral movement of the oocyte during injection. Oocytes injected with the system show better survival and enhanced expression of mRNA compared with those injected with a widely used type of manual injector (Coleman, 1984). PMID- 1865056 TI - Two-dimensional gel electrophoresis of the membrane-bound protein complexes, including photosystem I, of thylakoid membranes in the presence of sodium oligooxyethylene alkyl ether sulfate/dimethyl dodecylamine oxide and sodium dodecyl sulfate. AB - Two-dimensional polyacrylamide gel electrophoresis (PAGE), using a mixture of sodium oligooxyethylene alkyl ether sulfate and dimethyl dodecylamine oxide as detergents (AES-DDAO mixture) in the first dimension and sodium dodecyl sulfate (SDS) in the second dimension, was developed and applied to an analysis of the photosystem I (PS I) complex in thylakoid membranes prepared from spinach chloroplasts. When thylakoid membranes of chloroplasts were solubilized directly in the AES-DDAO mixture and subjected to PAGE in the presence of these detergents as the first dimension, some protein complexes containing chlorophyll were observed. The protein components in these complexes separated into an array of polypeptide spots when the strip of gel after PAGE in the first dimension was subjected to PAGE in the presence of SDS as the second dimension. The main band of protein which separated in the first dimension was demonstrated to be the PS I complex. This complex retained the intrinsic photochemical activity of P700 even after it was subjected to one-dimensional PAGE. These results suggest that certain protein complexes can be separated, with the maintenance of their original structures, by electrophoresis in the presence of the AES-DDAO mixture, and this method appears to have valuable potential for analysis of the components of membrane-bound protein complexes. PMID- 1865057 TI - Untreated tendon pathologies resulting in major functional disability. PMID- 1865058 TI - Comparison of oblique closing base wedge osteotomies of the first metatarsal: stripping versus nonstripping of the periosteum. AB - The authors present a study comparing two methods of performing the oblique closing base wedge osteotomy of the first metatarsal for correction of hallux abducto valgus deformity. In one group, the periosteum was stripped from the metatarsal prior to performing the osteotomy, and in the other group, the osteotomy was performed through the periosteum. Sixty-five osteotomies are included in the study. This article discusses the closing base wedge osteotomy, fracture healing and the role of the periosteum, the blood supply to the first metatarsal, and the effects of periosteal stripping. Also included is a presentation of the surgical technique used, a statistical review of the procedures performed, a critical discussion summarizing the results, and a discussion of the postoperative complications encountered. PMID- 1865059 TI - Tarsal tunnel syndrome secondary to neurilemoma of the medial plantar nerve. AB - A neurilemoma of the medial plantar nerve was observed in a 52-year-old Caucasian female. She was diagnosed with tarsal tunnel syndrome by clinical and electromyographic examination. This case was followed up for 18 months and has been presented as a very rare cause of tarsal tunnel syndrome. Relevant literature was reviewed. PMID- 1865060 TI - Pathologic afflictions of the Achilles tendon. AB - The Achilles tendon represents a very important structure in human locomotion. Pathologic afflictions of this tendon may lead to serious problems if not recognized and treated appropriately. Drs. Reinherz, Granoff, and Westerfield briefly review normal tendon anatomy and function. The mechanisms of tendon injury with clinical recognition of pathology, both objective and subjective, are then discussed. Proper management of the compromised tendo Achillis is presented. PMID- 1865061 TI - Old instrumentation with a new application: Smillie knife. AB - Foot surgery requires various dissection techniques through skin incisions with limited exposure. Although the unique knife was designed for knee surgery, its application for podiatric surgery is ideal. Through small skin incisions, the Smillie knife can use techniques to incise, excise, deglove, unzipper, and strip away soft tissue attachments from bone, cartilage, and other tissues. The Smillie knife or meniscutome is an instrument that is uniquely and specifically designed to allow precise dissection of designated structures. Thus, it maintains closely associated vital structures such as tendons, veins, arteries, and nerves undisturbed. PMID- 1865062 TI - Brachymetapody: case report of surgical correction. AB - Brachymetapody is an uncommon condition that can have both cosmetic and functional considerations. The literature is reviewed with respect to techniques for repair of short metatarsals. Surgical indications are discussed as well as techniques for repair. A case report of bilateral first and fourth metatarsal brachymetapody is reviewed with illustration of a successful surgical outcome after more than 5 years of follow-up. PMID- 1865063 TI - Distal extensor hallucis longus tenotomy. AB - This manuscript describes a clinical entity caused by hyperextension of the interphalangeal joint of the hallux and a corrective procedure performed percutaneously through a 3-mm. incision. A discussion of local anatomy, patient selection, and contraindications is included. Proper pre-operative assessment is stressed. PMID- 1865064 TI - Osteomyelitis of the foot in diabetic patients: evaluation with magnetic resonance imaging. AB - Magnetic resonance (MR) imaging examination was performed with a 1.5-Tesla superconducting magnet on a diabetic patient's right foot that had extensive deformities due to previous surgery, infection, and neuropathy. The purpose of the examination was to help identify areas of active infection in preparation for surgical debridement. This manuscript reviews current concepts on the use of radionucleotide scanning and computed tomography (CT) as compared to MR imaging when used to assist in the diagnosis of osteomyelitis in the diabetic foot. MR imaging was found to be useful in identifying areas of active bone infection in the presence of underlying osseous pathology when radiographic images and radionucleotide scans were unreliable. PMID- 1865065 TI - Ankle arthrodesis by the Heiple technique in rheumatoid arthritis. AB - The authors report on seven rheumatoid arthritic patients that successfully sustained ankle joint arthrodesis. They incorporated a chevron fusion technique previously described. Patients were followed an average of 44 +/- 11 months. They report a satisfactory result. PMID- 1865066 TI - Delayed appearance of metastatic renal cell carcinoma subcutaneously in the left fifth toe after ipsilateral nephrectomy. AB - Pedal metastases from visceral cancers, while rare, constitute a consideration in the presence of an otherwise unexplained mass in the skin, subcutis, or bones of the foot. Metastatic lesions may be presenting signs of visceral malignant tumors, or may remain occult for years after extirpation of the primary visceral lesion. The presented case depicts sudden activation and growth of an occult renal cell carcinoma metastasis in the subcutaneous tissue of a 69-year-old man's left fifth toe, 10 years after ipsilateral nephrectomy. Cytogenetic studies correlate with tumor histologic patterns and help to predict heritability, uni- or bilaterality, and local and systemic biologic behavior of renal cell carcinoma, thereby aiding in prognosis and treatment planning. PMID- 1865067 TI - Diagnosis and treatment of talar tilt and its relationship to the occurrence of transchondral fractures: a retrospective study. AB - A study of 112 acute ligamentous injuries of the ankle diagnosed with the Telos stress device and repaired surgically was conducted by the authors. They found that the likelihood of a transchondral fracture of the talar dome was significantly increased when the talar tilt was 18 degrees or greater. A significant number of these fractures were not diagnosed until surgical inspection. The authors provide a comprehensive review of transchondral fractures of the talar dome and attempt to correlate the clinical significance of the data obtained in this study with the diagnosis and treatment of these fractures. PMID- 1865068 TI - Long-standing reaction to a hemi-silastic implant. AB - The complications associated with the hemi-silicone implants of the foot have been well documented. Reasons for their failure are many. In the past, there has been an overuse of these devices without strict adherence to their proper indications. Today, these implant failures are being manifested by extremely unusual pathology. Although silicone has not been shown to be carcinogenic, the florid reaction seen in this case demonstrated a degree of "malignancy" that may have incapacitated the patient. PMID- 1865069 TI - Adventitial cystic disease. AB - Adventitial cystic disease is a rare syndrome predominantly seen in young males with the acute onset of claudication. Early diagnosis and confirmation with arteriography is of utmost importance to the success of treatment. The authors present a rare case report and treatment of adventitial cystic disease. PMID- 1865070 TI - Opening base wedge osteotomy with first metatarsophalangeal joint implantation arthroplasty--a retrospective study. AB - The authors present a retrospective study of the opening base wedge osteotomy with first metatarsophalangeal joint implant arthroplasty, for the correction of long-standing hallux abducto valgus deformity. Twenty cases involving 23 feet were performed, and the results are discussed. The indications and procedure are described, as well as an in-depth discussion. PMID- 1865071 TI - Endoscopic plantar fasciotomy: preliminary study with cadaveric specimens. AB - The authors have developed an endoscopic approach to a plantar fasciotomy. This technique would minimize the surgical trauma that is normally induced with a conventional type of heel spur surgery. The authors believe that this new technique will provide an earlier return to normal ambulation, less loss of work, and earlier, overall increased patient comfort. PMID- 1865072 TI - Pseudogout of the ankle: a case study and arthroscopic-assisted treatment. AB - Chondrocalcinosis, also known as pseudogout, a calcium pyrophosphate dihydrate crystal deposition disease, has been reported in many joints of the human body. A review of the literature reveals few reported cases of pseudogout of the ankle and various uncertainties of the etiology of pseudogout. The authors offer a review of the disease and a case presentation with the use of arthroscopy to assist in the diagnosis and treatment of pseudogout of the ankle. PMID- 1865073 TI - Tendon sheath injuries of the foot and ankle. AB - Tendon sheath injuries of the foot and ankle are a common clinical entity secondary to trauma and abnormal biomechanics. These injuries are often misdiagnosed and/or inappropriately treated. This article presents an historic review, etiology, classification, diagnosis, and treatment protocol for these injuries. PMID- 1865074 TI - Osteoid osteoma of the foot. AB - Dr. Wu discusses a benign osteoblastic neoplasm that accounts for less than 3% of all excised tumors. He reviews the symptoms of a 17-year-old, with pathology localized to the third toe. Clinical, radiographic, and histologic characteristics are described. PMID- 1865075 TI - Pharmacology of nonsteroidal anti-inflammatory drugs. AB - Various medications are used by the lower extremity surgeon that affect the entire body. Nonsteroidal anti-inflammatory drugs are one such class. The authors review certain commonly used pharmaceuticals in this category, comparing the basic characteristics of each one. PMID- 1865076 TI - Diagnostic imaging approach to bone tumors of the foot. AB - The authors review various bone tumors in the foot. They use ten key points with respect to five levels of evaluation, in order to assist the clinician in rapid recognition of these maladies. The classification system relates to plain x-ray films, although the authors also illustrate other sophisticated radiologic techniques for increased accuracy. PMID- 1865077 TI - Sex differences in growth hormone response to growth hormone-releasing hormone. AB - The aim of the present study was to ascertain whether sex differences exist in GH response to GHRH, and the influence that menstrual cycle have on this response. A GHRH test was performed on nine healthy men and ten women on days one and twelve of the menstrual cycle. Basal GH levels, (mean +/- SE) (7.98 +/- 3.09 ng/ml in women and 0.13 +/- 0.07 ng/ml in men, p less than 0.05) as well as maximal GH response (40.17 +/- 11.96 ng/ml in women and 9.63 +/- 2.32 ng/ml in males, p less than 0.01) were significantly higher in women than in men. In spite of a significant increase in estradiol levels during the menstrual cycle (75.88 +/- 2.48 pg/ml on day one and 198.40 +/- 28.65 pg/ml on day twelve, p less than 0.01) neither basal plasma GH levels, nor GH response to GHRH were significantly different. In conclusion, these results confirm that GH response to GHRH is higher in women than in men, and that this difference is not modified during the first phase of the menstrual cycle. PMID- 1865078 TI - Glucagon-induced changes in plasma thyroid hormone concentrations in healthy dogs resemble "euthyroid sick syndrome". AB - We recently demonstrated that glucagon infusion induced a decline in T3 and a rise in rT3 in anesthetized dogs. These changes in T3 and rT3 may be attributed, at least in part, to anesthesia itself, since general anesthesia is known to cause lowering of T3 and an elevation in rT3 during the perioperative period. Therefore, to eliminate the contribution, if any, of anesthesia to these changes in T3 and rT3, we assessed plasma glucose, T3 resin uptake (T3RU), T4, free T4, T3 and rT3 concentrations following intravenous glucagon (0.5 mg) or normal saline (0.5 ml) administration at frequent intervals for 3 h in 6 conscious dogs fasted for 16 h. No significant alterations were noted in T4, free T4, and T3RU levels during either study. However, glucagon infusion alone induced a significant fall in T3 (0.33 +/- 0.06 in nmol/l vs -0.03 +/- 0.03 nmol/l with normal saline; p less than 0.01) and marked elevations in glucose (3.66 +/- 0.22 mmol/l vs 0.61 +/- 0.11 nmol/l with normal saline, p less than 0.001) and rT3 concentrations (0.11 +/- 0.02 nmol/l vs 0.005 nmol/l; p less than 0.001). Furthermore, the integrated responses of T3 and rT3 as assessed by cumulative changes and areas under the curves were markedly greater during glucagon infusion when compared with saline administration (p less than 0.01 for all comparisons). Since the elevations in levels of stress hormones known to ensue during anesthesia do not occur during a conscious resting state, we believe that hyperglucagonemia may be a major contributor of thyroid hormone alterations observed in several euthyroid sick states, not associated with stress, and may enhance these changes during euthyroid sick syndrome associated with stressful crises. Finally, these changes may be attributed to altered metabolism of iodothyronines in peripheral tissues as reflected by lowered T3/T4 and increased rT3/T4 ratios. PMID- 1865079 TI - Islet cell surface antibodies by an ELISA method in diabetic and nondiabetic patients. AB - Islet cell surface antibodies (ICSA) were investigated by an ELISA method using a commercial kit in 146 subjects with and without islet cell antibodies (ICA): 28 with insulin-dependent diabetes mellitus (IDDM), 24 with noninsulin-dependent diabetes mellitus (NIDDM), 22 first-degree relatives (FDR) of IDDM patients, 31 organ-specific autoimmune patients (OSAP), 21 nonautoimmune hospitalized patients (NAP), and 20 ICA-negative normal controls. Furthermore, insulin autoantibodies (IAA) were evaluated in 87 of these subjects. ICSA were found in 11% of IDDM patients and in 14% of their FDR, in 4% of NIDDM patients, in 10% of OSAP, in 10% of NAP, and in 5% of normal controls. After absorption with rat liver powder, ICSA were detected in 7% of IDDM patients, in 5% of their FDR, in 4% of NIDDM, in 6% of OSAP, in 5% of NAP and in none of normal controls. ICSA were also detected in 4% of IAA-positive compared to 3% of IAA-negative sera. Neither correlation was found between ICSA and ICA in each group of subjects, nor between ICSA and IAA, suggesting that these autoantibodies recognize different pancreatic targets. Moreover, no significant difference was observed for ICSA prevalence in the various groups of patients studied when compared with normal controls. The prevalence of ICSA assessed by this ELISA method has been compared to that reported by other workers, who employed different techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865080 TI - Coexisting hyperparathyroidism with thyrotoxicosis. AB - The coexistence of hyperparathyroidism complicating thyrotoxicosis is quite rare. We report the case of one patient who presented with thyrotoxicosis, (total thyroxine of 15.1 micrograms/dl (5-13), free thyroxine index of 18 (4-15) and triiodothyronine by RIA of 305 ng/dl (70-230) and asymptomatic hypercalcemia of 15 mg/dl (8.5-10.6), who was also initially noted to have an elevated (C terminal) serum immunoreactive parathyroid hormone (iPTH) level of 8,800 pg/ml (50-340). With propylthiouracil and propranolol, however, this patient became normocalcemic with a decrease in iPTH values to 714 pg/ml. As the patient was tapered from medication, after being rendered euthyroid, a recurrence of hypercalcemia with rising iPTH levels occurred. PTH levels should be helpful in defining coexisting hyperparathyroidism in patients with thyrotoxicosis since in the latter iPTH is usually suppressed. Our findings support the recommendation that in patients suspected of having both hyperparathyroidism and hyperthyroidism, a diagnosis of the former can only be made with certainty after the patient has been rendered euthyroid with persistently elevated serum calcium and iPTH levels. While there are no clinical features which permit the easy identification of patients who present with dual lesions, the determination of iPTH values may be the most consistently helpful test initially, whereas other parameters such as vitamin D, serum phosphate are less reliable. PMID- 1865081 TI - In vitro production of estradiol by ovarian granulosa cells in a case of McCune Albright syndrome. AB - A 14-year-old girl presented with classic McCune-Albright syndrome. She underwent the ablation of several cysts during a laparotomy performed on the basis of persistent and intense pelvic pain and recurrent episodes of menometrorrhagia not responsive to pharmacologic therapy. Granulosa cells obtained from an isolated follicle and a cyst were cultured and estradiol (E2) secreted in the culture medium measured. Granulosa cells, obtained from the follicle, produced much higher levels of estradiol compared to those of cells coming both from follicles of equivalent size and preovulatory follicles of normal patients. Secretion of E2 by granulosa cells from the cyst was comparable to that of normal preovulatory follicles. We conclude that in this patient, ovaries are hyperfunctioning in terms of E2 production. This high production of estradiol and the fact that several cysts were found in the ovaries can justify the high levels of estradiol found in the serum of this patient at the moment of the operation. PMID- 1865082 TI - Insulin-like growth factor I: a good indicator of functional hepatocellular capacity in alcoholic liver cirrhosis. AB - To assess the value of serum insulin-like growth factor I (IGF-I) determination in liver disease, 21 patients hospitalized for active alcoholic cirrhosis (19 males, 2 females), 56 +/- 2 y (mean +/- SE) were studied at admission. Individual scores of hepatic alterations (Child score) ranged from 6 to 12 (mean: 9 +/- 1). Basal IGF-I levels were dramatically decreased, averaging 0.11 +/- 0.02 U/ml vs 0.70 +/- 0.08 U/ml in 15 control subjects. In cirrhotic patients, IGF-I values were inversely correlated with the modified Child index (r = 0.57, p less than 0.01). A highly significant positive correlation (r = 0.68, p less than 0.001) was evidenced between IGF-I levels and aminopyrine breath test values (which provide quantitative estimates of the hepatic functional capacity). In contrast, no significant relationship was found between IGF-I levels and various nutritional parameters (albumin, prealbumin, retinol binding protein) after partial correlation analysis. The present data suggest that, in alcoholic cirrhosis, the decrease of circulating IGF-I values is mainly related to alterations of liver function, and that IGF-I can be used as a good indicator of functional hepatocellular capacity. PMID- 1865084 TI - Health-care practices of the rural aged. AB - 1. One of the primary concerns of the rural aged is the maintenance of their physical health so that they may function independently and remain in their own homes. 2. The findings of this study indicate that most older rural adults do not regularly have positive health-care practices. This may be due to the unavailability of health-care providers or health promotion programs in isolated rural areas. 3. Implications of this study include the need to make health promotion programs relevant to the concerns of the rural aged rather than those of the urban elderly. PMID- 1865085 TI - Essential gerontological content for the associate degree nursing curriculum. A national study. AB - 1. The growing number of associate degree registered nurses caring for the elderly underscores the need for gerontological nursing preparation within associate degree programs. 2. The curriculum content validity theory of Taba and Zoot requires content selection criteria to reflect the relationship of course content to program outcomes. 3. Appropriateness of gerontological content for associate degree nursing was defined by the five practice roles of the associate degree nurse. 4. Gerontological nursing content rated essential by nationwide panels of associate degree nursing educators and practicing nurses includes items within the areas of commonly encountered health problems, ethical issues, chronic illness, long-term care of older adults, and nursing process. PMID- 1865086 TI - Why walk when you can ride? Clinical ambulation incentives for the immobile elderly. AB - 1. Gerontological nurses in long-term care settings should be selective in the use of wheelchairs for residents with ambulation ability. 2. The gerontological nurse specialist can facilitate change in a long-term care setting through the implementation of an ambulation incentive program. 3. The benefits of an ambulation incentive program support rehabilitation-focused care as opposed to custodial care in a long-term care facility. 4. Quality of life outcomes for elderly residents are supported through multidisciplinary collaboration in the implementation of an ambulation program. PMID- 1865087 TI - Using previous knowledge to teach elderly clients. AB - 1. Fluid intelligence decreases while crystallized intelligence continues to increase over the life span. 2. Nurses should determine what patients already know about how to care for themselves. 3. Nurses may help patients to learn better by intentionally basing new information on what patients already know. PMID- 1865088 TI - Multistix versus laboratory urinalysis in the detection of urinary tract infection. AB - 1. Difficulty with the early recognition of infection is a problem when caring for patients in an extended care facility. 2. The ability to quickly differentiate between asymptomatic bacteriuria and actual infection in male extended care patients is useful for guiding antibiotic therapy. 3. The nurse administered nitrite test proved reliable as an indicator or urinary tract infection. PMID- 1865089 TI - Clinically managing disruptive behavior on the ward. AB - 1. The inability to manage disruptive yelling has lead to the overuse of physical restraints, inappropriate use of psychotropic medications, and provoked feelings of powerlessness, helplessness, and frustration among caregivers that could detract from the overall quality of care. 2. Behavioral analysis provides a framework for caregivers to identify, modify, and develop practical means to alleviate and to monitor a problem. 3. Noisy behavior can become more manageable by combining the effects of improved environment, continuous monitoring and simplification of medication, individualized nursing care, and a sense of creativity. 4. Caregivers need to examine their own feelings and behavior and to understand that they have a responsibility to create an environment in which their clients can respond positively. PMID- 1865090 TI - Two decades of advancement in the assessment of fetal health. AB - Over the past twenty years there has been a substantial refining and extension of the tests available for the assessment of fetal health. This has particularly been related to the developed of reasonably-priced real-time ultrasound and an improved understanding of the relationship between aspects of fetal behaviour and state and fetal health. The impact of these developments is briefly reviewed. PMID- 1865091 TI - Behavioural assessment of fetal health. AB - The assessment of behavioural activity of the fetus is widely used to assess fetal health in clinical practice as part of the biophysical profile as well as the nonstress test. Considerable information regarding normal activity patterns of healthy human fetuses have been obtained from 24 to 40 weeks gestation. It is this information which has provided the scientific foundation for the development of fetal assessment protocols. Studies in chronically-catheterized fetal sheep have demonstrated that acute hypoxemia leads to an inhibition of fetal breathing movements although prolonged reductions in oxygen delivery to the fetus in the absence of acidemia are associated with adaptation by the fetus and subsequent return to normal incidence of behavioural activity. The behavioural responses of the fetus to specific stimuli including vibroacoustic stimulation have been examined in relation to gestational age as well as type of stimulus, it is proposed that fetal acoustic stimulation could possibly be used to assess fetal neurological function although prior to it being accepted as an universal method for assessing fetal health it is essential that a greater understanding of the mechanisms involved in fetal responses to sound and vibration be determined using appropriate experimental techniques. PMID- 1865092 TI - Use of Doppler technology in assessing fetal health. AB - Doppler technology has provided new information about the fetus during intrauterine life. Changes in red cell velocity in the umbilical artery relate well to changes in downstream resistance in the placenta. Resistance (or more correctly impedance) appears to be closely linked to the number of small fetal arterioles in the tertiary stem villus. Placental pathology leading to a reduction in these arterioles is often associated with severe intrauterine growth restriction and poor perinatal outcome. Whilst there is no good evidence that screening women with low risk pregnancies is clinically useful, umbilical artery Doppler information would appear to be useful in the management of pregnancies already identified as at risk. Here abnormal Doppler findings suggest the need for maternal rest, increased fetal surveillance and early delivery when indicated. PMID- 1865083 TI - The interaction between mediobasohypothalamic dopaminergic and endorphinergic neuronal systems as a key regulator of reproduction: an hypothesis. PMID- 1865093 TI - Assessment of regionalized perinatal programs. AB - This paper addresses issues encountered in studies of the effectiveness of regionalized perinatal care. Regionalization of perinatal care has been actively promoted based upon the intuition that regionalization should reduce perinatal mortality and morbidity. When assessing the effectiveness of a perinatal service, one is interested in whether the service is being utilized appropriately and, if utilized appropriately, whether it is impacting upon outcome. Studies of utilization of regionalized perinatal care include studies of: utilization of the tertiary centre, non-utilization of the tertiary centre and antenatal transfer patterns. Studies of program impact are few. There is one quasi-experimental study which examines mortality and morbidity impact of a program and a few studies examining indirect hypotheses of the impact of regionalization on mortality. Despite the sparsity of the literature, there is evidence in the papers reviewed that regionalization of care may have impact on both mortality and morbidity. Further studies of the latter are needed. Further studies might also include measures of satisfaction of care providers, satisfaction of patients and maternal attachment, among others. In addition, since preliminary evidence implies that regionalized perinatal care is effective, future studies might include considerations of cost-effectiveness. PMID- 1865094 TI - The trigger for parturition in sheep: fetal hypothalamus or placenta? AB - The fetal pituitary-adrenal axis plays a pivotal role in the mechanisms leading to parturition in sheep. Fetal cortisol concentrations gradually increase in the last 15 days before term, with a marked increase occurring in the last 3-4 days. Some mechanism causes a marked increase in the stimulatory drive to the fetal pituitary resulting in increased secretion of ACTH from the pituitary, and subsequent cortisol secretion from the adrenal gland. In this paper we discuss the roles of the hypothalamus and placenta in triggering the onset of labour in sheep. We have shown that prostaglandin E2 can stimulate the release of ACTH and cortisol in the intact fetus and we believe that this could be mediated by the release of CRH and AVP. Although CRH and AVP are present in the fetal hypothalamus and are capable of being released, these factors may not be released until approximately 135 days of gestation. One fundamental question in relation to parturition remains unanswered: how are the high concentrations of cortisol in fetal plasma sustained given that cortisol has an inhibitory feedback effect on the release of CRH and ACTH secretion? We discuss the possibility that the placenta provides an additional trophic drive to both the pituitary and adrenal glands which contributes towards the sustained elevated cortisol concentrations needed to initiate parturition. The placenta may initiate the hypothalamus and PGE2 and/or CRH, secreted by the placenta, may stimulate pituitary ACTH release. PMID- 1865095 TI - Control of glucose metabolism in the perinatal period. AB - The central importance of glucose as a fuel for energy metabolism and growth of the fetus is clear as is the role of insulin in coordinating its utilisation by many fetal tissues. What is less clear is the qunatitative nature of the interaction between the fetus and placenta in organising glucose metabolism. Increasingly there is evidence that the fetus coordinates some of the supply of glucose to the placenta and that this is particularly important when uterine blood flow is reduced. It is unclear how this is regulated, but substrate cycles of glucose and lactate appear to make a significant contribution to carbohydrate metabolism in fetus and placenta. Another area as yet unresolved in the control of fetal glucose metabolism is the coordination of the changes that occur around the time of birth. Notable of these is the activation of glycogen mobilisation and of glucose synthesis and changes in the setting of glucose regulatory mechanism. These are briefly reviewed. PMID- 1865097 TI - Methicillin-resistant Staphylococcus aureus in long-term care facilities. PMID- 1865098 TI - Strategies for disinfection and sterilization of endoscopes: the gap between basic principles and actual practice. PMID- 1865096 TI - Paracrinology of growth regulation. AB - Embryonic and fetal growth is dependent on genetic factors and epigenetic factors such as peptide growth factors. We describe here the interactions of several peptide growth factors during the growth and function of two cell types, growth plate chondrocytes from the ovine fetus and astroglial cells from the newborn rat cerebral cortex. Isolated chondrocytes released two endogenous growth factors, basic fibroblast growth factor (bFGF) and insulin-like growth factor II (IGF II). Although the latter was released in greater abundance, as detected by radioimmunoassay, exogenous bFGF was more than a thousand fold more active as a mitogen. Insulin was also able to increase chondrocyte replication at physiological concentrations, and bFGF, insulin and IGFs were additive in their effects on DNA and protein synthesis. Transforming growth factor beta (TGF beta), which is abundant in bone, had little effect on chondrocyte DNA or total protein synthesis alone, but blocked the stimulatory actions of insulin and IGFs on these parameters. However, TGF beta when alone or in combination caused an increase in the collagen: non collagenous protein ratio of new proteins synthesized by chondrocytes. Adult rat brain is a rich source of IGF II, and both IGF I and II are present during neurogenesis and gliagenesis in the fetal and neonatal rat respectively. We have cultured astroglial cells isolated from neonatal rat cerebral cortex to examine the production and interaction of peptide growth factors during their growth. Isolated astroglial cells contained mRNAs encoding both IGF I and II but abundance was not regulated by other hormones or growth factors. Using affinity cross-linking we found that cultured cells also released two species of IGF binding protein (IGF-BP) of 33 kDa and 38 kDa. Northern blot analysis using homologous cDNA probes showed that astroglial cells expressed IGF BP2 and BP3, but little BP1. Both IGF I and II were mitogenic for astroglial cells, as was insulin at physiologic concentrations. Exogenous IGF-BP2 was able to modulate the mitogenic actions of exogenous IGF I. These two very different cell models show many similarities of endogenous growth control. Both release IGFs and IGF-BPs which regulate mitogenic rate. In addition, in both insulin functions as a growth factor at physiologic concentrations. These findings suggest common principles governing embryonic and fetal growth and development. Studies have shown that fetal and neonatal growth is independent of regulation by classic hormones (e.g. growth hormones) synthesized by the mother or the fetus. It is believed that embryonic and fetal growth is controlled by two major mechanisms, namely, (i) the genetic factors as determined by the embryonic and fetal genome, and (ii) the epigenetic and environmental factors that alter the expression of the embryonic or fetal genome.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1865099 TI - Infection control practices in gastrointestinal endoscopy in the United States: a national survey. AB - OBJECTIVE: To ascertain current infection control practices, endoscope cleaning procedures, perceived risks of infection, and implementation of universal precautions in gastrointestinal endoscopy units in the United States. DESIGN: National mailed survey of gastroenterology nurses and associates conducted anonymously in March 1988. SETTING: Completed surveys were received from all 50 states and Puerto Rico and from all practice settings. The most common practice setting was private/community hospitals (66%). PARTICIPANTS: Of the 4,952 survey forms mailed to all members and to interested nonmembers of the Society of Gastrointestinal Nurses and Associates, 2,158 (44%) were returned and 2,030 (41%) were completed and evaluable. Of the respondents, 1,487 (73%) were registered nurses. RESULTS: Sixty-seven percent (n = 1,358) of the respondents routinely used an enzymatic cleaner as a step in the instrument decontamination process; 93% (n = 1,879) chemically disinfected instruments after each case; and 88% (n = 1,779) disinfected endoscopes with an aqueous glutaraldehyde product. Respondents reported that they and a significantly smaller proportion of physicians (p less than .001) employed barrier precautions for all endoscopic cases involving possible contact with blood/body fluids of patients known (66% versus 57%, respectively) and not known (12% versus 8%, respectively) to have a bloodborne infection. Endoscopy-related infections, usually bacterial, were reported to have occurred at their institutions by 6% (n = 116) of respondents. CONCLUSIONS: We conclude that cleaning, disinfection, and sterilization procedures for gastrointestinal endoscopic instruments vary, that appropriate protective apparel is not always worn, and that some practices may lead to preventable endoscopy related infection in patients. PMID- 1865100 TI - Investigations of intrinsic Pseudomonas cepacia contamination in commercially manufactured povidone-iodine. AB - OBJECTIVE: Laboratory investigations were initiated with a povidone-iodine antiseptic solution that was intrinsically contaminated with Pseudomonas cepacia. These investigations were helpful in understanding the microbicidal and chemical properties of iodophor solutions and the mechanism by which P cepacia can survive in iodine-containing antiseptics. DESIGN: Included in these studies were: prolonged survival of P cepacia; available and free iodine determinations; microbial challenge studies; and scanning electron microscopic examination of contaminated antiseptic. RESULTS: P cepacia survived in this iodophor antiseptic up to 68 weeks from the date of manufacture. A uniform concentration of 1% available iodine was found in all lots of povidone-iodine tested as specified on the product label, but free iodine (I2) values varied greatly. Low free iodine levels of 0.23 to 0.46 ppm were associated with the contaminated lot of povidone iodine. Solutions of povidone-iodine with varying levels of free iodine were rapidly microbicidal when challenged with cells of P cepacia derived from culture broth and washed or adapted to growth in water. P cepacia cells taken directly from contaminated povidone-iodine survived for significantly longer periods of time. Large numbers of P cepacia were found embedded in extracellular material and among strands of glycocalyx between cells as shown by scanning electron microscopy. CONCLUSIONS: The physical thickness of cellular and extracellular material that forms on surfaces could protect embedded organisms from the microbicidal action of disinfectants and antiseptics and subsequently allow for extended microbial survival times. Manufacturers should be aware that distribution piping surfaces colonized with bacteria may be a source of product contamination and resistant organisms. PMID- 1865101 TI - Epidemiology of isolation precautions. AB - OBJECTIVE: To investigate compliance with isolation precautions. DESIGN: A prospective observational study carried out during ten weeks of 1989. Participants were unaware of the study. SETTING: The isolation bay of a 24-bed surgical intensive care unit in a 900-bed university tertiary care facility. PARTICIPANTS: Study participants included any healthcare worker or visitor entering the patient room during designated 15-minute intervals. RESULTS: We observed 467 subjects entering patient rooms. Compliance with strict isolation (65%) was better than with wound/skin (40%) or excretion/secretion (36%) isolation (p less than .01). Visitors were more compliant than healthcare workers (88% versus 41%; p less than .01). Spending more time in the room was associated with improved compliance (p less than .01). Compliance was higher for subjects entering with a group compared with those entering alone (51% versus 41%; p less than .05). The compliance rate for nurses improved as the nurse/patient ratio improved (p = .14). Compliance was independent of severity of illness. Multivariate analysis revealed that the amount of time spent in the room, being a visitor, and use of strict isolation were independent predictors of compliance. CONCLUSIONS: Noncompliance was widespread. When increased demands are placed on the time of physicians and nurses in the name of cost containment, unperceived consequences, such as those resulting from decreased compliance, must be considered. PMID- 1865102 TI - Emperor's clothing for the contemporary healthcare worker. PMID- 1865103 TI - Monitoring and evaluation. PMID- 1865104 TI - Epidemiologic typing systems for coagulase-negative staphylococci. PMID- 1865105 TI - Combination of in situ hybridization and immunocytochemistry to detect messenger RNAs in identified CNS neurons and glia in tissue culture. AB - We have developed a technique in which immunofluorescence is combined with in situ hybridization using cDNA and RNA probes to assess the expression and distribution of messenger RNAs (mRNA) by neurons and neuroglia in tissue cultures of the rat dentate gyrus. The probes used in this study include a cDNA probe for ribosomal RNA (rRNA) and an RNA probe (cRNA) for glial fibrillary acidic protein (GEAP), an intermediate filament protein subunit expressed by astrocytes in the central nervous system. Both ubiquitous (tubulin) and cell type-specific (MAP-2 and GEAP) antibodies were used to identify neurons and neuroglia in culture. Using this procedure, the mRNA for rRNA was found in the cell bodies and large processes of MAP-2-positive neurons and throughout the cytoplasm of GEAP-positive flat astrocytes. In process-bearing astrocytes, GEAP mRNA is concentrated in the cell body, although some hybridization also occurred in astrocyte cell processes. With this combined in situ hybridization-immunofluorescence technique, the expression and distribution of an mRNA can be examined in different immunocytochemically identified cell types under identical culture and hybridization conditions. It is also possible to determine if there is a differential subcellular distribution of an mRNA in a single cell and if the distribution of the mRNA reflects the distribution of the protein itself. Finally, this technique can be utilized to verify the specificity of probes for cell type-specific mRNAs and to determine appropriate hybridization conditions to produce a specific signal. PMID- 1865106 TI - Basic fibroblast growth factor binding is a marker for extracellular neurofibrillary tangles in Alzheimer disease. AB - Neurofibrillary tangles (NFT) are abnormal filamentous inclusions that develop in neurons in Alzheimer disease and other disorders. When neurons die, the neurofibrillary tangles that persist in the extracellular space show ultrastructural and antigenic changes. Both intra- and extracellular NFT have recently been shown to contain heparan sulfate proteoglycans (HSPGs). HSPGs are also present in other amyloid deposits in the brain and in systemic amyloidoses. Basic fibroblast growth factor (bFGF) is a heparin binding growth factor which is involved in angiogenesis and also has neurite promoting activity. We now report that bFGF binds avidly to extracellular NFT. Alz-50, a monoclonal antibody (MAb) to an abnormal form of tau and bFGF binding label mutually exclusive subpopulations of neurofibrillary tangles. bFGF binding is abolished by heparinase or heparitinase treatment and therefore is most likely based on the presence of HSPG. Binding of bFGF is a specific and sensitive morphological method to distinguish intra- from extracellular NFT. As intracellular NFT, which also contain HSPGs, are not labeled by bFGF binding, this finding also suggests that HSPGs are modified when the NFT become extracellular. PMID- 1865107 TI - Production and characterization of osteoclast-selective monoclonal antibodies that distinguish between multinucleated cells derived from different human tissues. AB - Osteoclastoma-derived giant cells were used to produce 11 mouse monoclonal antibodies (MAb) reactive against human osteoclasts on undecalcified sections of adult human bone. All exhibited unique reactivities across a wide range of human tissues. Three in particular demonstrated distinctive reactivities; C35 was highly selective for bone osteoclasts, C27 showed selective reactivity for osteoclasts, tissue macrophages and blood-borne monocytes, and C22 showed selective membrane staining of osteoclasts. Consequently, C22 was used to coat Dynabeads to affinity-purify viable human osteoclasts from osteoclastoma-derived cell suspensions. Immunocytochemical staining of inflammatory osteoarthritic synovium/granulation tissue demonstrated positivity in the majority of giant cells with MAb C22 and C27. In contrast, C35 reacted with only very occasional giant cells. Furthermore, multinucleated cells formed in long-term human bone marrow cultures demonstrated similar selective staining. C27 stained all giant cells and the majority of mononuclear cells. C22 detected only a small proportion of giant cells. In contrast to its staining on bone osteoclasts, C22 demonstrated granular cytoplasmic staining in cultured giant cells. C35 stained no cells at all in these cultures. These MAb can therefore distinguish between giant cells of various origins and authentic mature osteoclasts. Alternatively, they can recognize antigens expressed at different stages of osteoclast differentiation and therefore provide an excellent tool for the study of the human osteoclast lineage. PMID- 1865108 TI - Immunocytochemical demonstration of a pancreatic secretory protein of unknown function in human duodenum. AB - We have previously isolated from human pancreatic juice a secretory glycoprotein of 19 KD (P19), devoid of known enzymatic activity. P19 gave by proteolysis a protein of 14 KD (P14), at first named protein X and also called pancreatic thread protein or pancreatic stone protein. Specific rabbit immunosera prepared against P19 and P14 were applied to localize these proteins in human small intestine. By comparison, antibodies directed against some human pancreatic enzymes (amylase, lipase, chymotrypsin, trypsinogen 1, trypsinogen 2, and trypsin 1) were also tested. Positive immunoreactivity was observed on Paneth cells with antisera directed against trypsinogens, trypsin 1, and P19-related proteins. In addition, antisera directed against P19-related proteins stained the columnar cells located in the crypts of Lieberkuhn. These original findings are a further indication of the resemblance between Paneth and pancreatic acinar cells but show that their functional analogy is only partial. On the other hand, the presence of P19-related proteins on non-mature columnar cells suggests that this differential distribution is a consequence of differentiation. PMID- 1865109 TI - R-phycoerythrin as a fluorescent label for immunolocalization of bound atrazine residues. AB - We established a highly sensitive immunofluorescence procedure for localizing bound atrazine in the aquatic macrophytes Elodea canadensis and E. densa. The technique included biotin-labeled anti-rabbit IgG as a first enhancement step and R-phycoerythrin (R-PE) coupled to streptavidin for fluorescent labeling as a second improvement on the procedure. A comparison with the conventional indirect immunofluorescence method confirmed the superior results of the R-PE approach. The use of atrazine-free plants (grown in charcoal-filtered water) and a variety of other controls excluded both contaminating atrazine and nonspecific incubation constituents as sources of tissue staining. Pre-incubations to block nonspecific binding sites proved to be unnecessary in this system. The highly sensitive procedure described here might be a useful tool for the localization of tissue bound pesticides in general and possibly of other haptens as well. PMID- 1865111 TI - Enhanced resolution of histochemical distribution of glucose-6-phosphate dehydrogenase activity in rat neural tissue by use of a semipermeable membrane. AB - We examined the histochemical distribution of glucose-6-phosphate dehydrogenase (G6PD) activity in neural tissue using different diffusion barriers. Although polyvinyl alcohol and agar overlays permitted regional localization of G6PD, a semipermeable membrane revealed cellular differences in G6PD activity within populations of neurons. Distribution of G6PD activity in selected regions of the nervous system was examined using the membrane technique. White matter usually exhibited strong G6PD activity. The neuronal somata of the dorsal root ganglia (L4-L6) and anterior horns of the spinal lumbar enlargement demonstrated a variation in activity which was independent of somal size. Satellite cells showed intense activity when the membrane technique was used. Hippocampal pyramidal and granular cells of the dentate gyrus exhibited moderate, uniform G6PD activity, but only weak activity was seen in hippocampal and dentate molecular layers. High levels of activity were observed in the vascular endothelial cells of the brain, spinal cord, and choroid plexus, and in the ependymal cells of the spinal central canal and ventricles of the brain. The superior vestibular nucleus appeared to have little G6PD activity in either the neuron cell bodies or the surrounding parenchyma. The use of a semipermeable membrane for localization of G6PD activity in neural tissues permits enhanced resolution of neuron elements and may provide a more accurate assessment of G6PD activity in histological preparations. PMID- 1865110 TI - Androgen receptor expression in human tissues: an immunohistochemical study. AB - The cellular localization of the human androgen receptor was visualized immunohistochemically using a mouse monoclonal antibody (MAb) F39.4, directed against a fragment of the N-terminal domain of the androgen receptor. The nuclear immunoreactivity of various human tissues with F39.4 was generally consistent with earlier biochemical and autoradiographic data. However, previously suggested androgen receptor expression in thyroid, pancreatic, gastrointestinal, and bladder tissues was not confirmed immunohistochemically. Stratified squamous epithelia of vagina and cervix showed selective immunostaining of the basal cell layer, whereas in the preputial epithelium the intensity of immunoreactivity decreased gradually with maturation. In contrast, glandular epithelia of the sweat glands, male accessory sex organs, and female breast showed nearly exclusive F39.4 staining of the inner cylindric layer. In the testis, Sertoli cells, peritubular myoid cells, and interstitial cells were immunoreactive with MAb F39.4. Expression of the androgen receptor by smooth muscle tissue was largely confined to the male reproductive organs. The specificity and sensitivity of this simple and rapidly performed immunohistochemical technique in the detection of the human androgen receptor at the cellular and subcellular level makes it worthwhile to study tissue androgen receptor expression by immunohistochemistry in physiological and pathological states. PMID- 1865112 TI - Quantitative immunocytochemistry of rat submandibular secretory proteins during chronic isoproterenol administration and recovery. AB - We utilized quantitative electron microscopic immunogold labeling procedures to follow changes in the intragranular content of five secretory proteins of the rat submandibular gland (SMG) during and after chronic treatment with the beta adrenergic agonist isoproterenol (IPR). Labeling intensities (gold particles/microns2) of acinar cell secretory granules for mucin and glutamine/glutamic acid-rich proteins, major secretory proteins of the normal SMG, showed opposite responses to IPR. Labeling intensities increased for mucin and decreased for glutamine/glutamic acid-rich proteins immediately after IPR injections began, then rapidly returned to control levels after cessation of IPR treatment. SMG Protein C immunoreactivity, found in both acinar and intercalated duct granules, was less affected by IPR. However, opposite changes in labeling intensity were observed between acinar and intercalated duct granules. Labeling intensities for proline-rich proteins, IPR-inducible secretory proteins, increased only after 10 days of stimulation and maintained a high level even after cessation of drug treatment. Type 2 cystatin, another IPR-inducible protein, increased gradually with chronic IPR treatment and decreased slowly during the recovery phase. These results suggest that chronic beta-adrenergic stimulation affects the expression of genes for several rat SMG secretory proteins in a different manner. PMID- 1865113 TI - Immunohistochemical characterization of a crypt cell-specific plasma membrane protein in rat small intestine epithelium using a monoclonal antibody. AB - Proteins of the basolateral membrane (BLM) of small intestine epithelial cells of adult rats, in the MW ranges of 50-65 KD, 85-100 KD, and over 100 KD, were obtained as follows. After isolation of the BLM and subsequent SDS-PAGE and transblotting of the proteins on nitrocellulose sheets, the bands in these MW ranges were cut out of the nitrocellulose sheet and extracted. Balb/C mice were immunized with these protein fractions and a monoclonal antibody (MAb) was then produced. MAb SI/CC1 obtained via immunization with the 50-65 KD protein fraction shows specificity for the crypt epithelium of the small intestine. It can be used to characterize, by light and electron microscopic immunohistochemical methods, a crypt cell protein (SI/CC1-Ag) with a very specific localization. Fluorescence labeling shows that the SI/CC1-Ag can be found only in the epithelium of small intestine crypts (except for the granules in eosinophilic granulocytes). The epithelium of the colon, as well as the epithelia of other organs, could not be labeled. In the small intestine crypts, SI/CC1-Ag is found only in the Paneth cells located in the basal crypt section, and in the undifferentiated cells in the middle crypt section; it is lacking in the cells of the upper crypt section. Gold labeling shows that SI/CC1-Ag in the undifferentiated cells is localized exclusively in the basolateral PM domain. On the Paneth cells, the content of the secretory granules is labeled, along with the basolateral PM domain; the labeling sometimes present on their luminal part is probably due to passively absorbed secretion from these cells. The SI/CC1-Ag in the BLM of undifferentiated and Paneth cells is found only on Days 21-23 post partum, whereas the Paneth cell granules could be labeled as early as the Day 16 post partum. With immunodetection with SI/CC1, one band at about 55 KD is specifically labeled in the protein pattern of the isolated small intestine cell BLM. In the protein pattern of the isolated crypt cells two bands were labeled, again one at 55 KD and one at about 120 KD. These findings indicate that SI/CC1-Ag is a 55 KD protein that appears on Days 21-23 post partum in the BLM of undifferentiated cells and of Paneth cells. PMID- 1865114 TI - Antibodies to tubulin and actin bind to the surface of a human monocytic cell line, U937. AB - Intermittent reports of cytoskeleton proteins (actin and tubulin) on the cell surface have appeared over the last 13 years. Whereas most have concentrated on lymphocytes, this study provides evidence for the presence of these proteins on the surface of a human cultured monocyte-like cell line, U937. Both actin and tubulin were detected on the surface of U937 cells by flow cytometry, using an indirect staining procedure based on biotin-streptavidin-phycoerythrin, chosen for greater sensitivity. By use of this procedure, the majority of viable unstimulated U937 cells stained positively for actin and tubulin, although the level of fluorescence intensity was low. With an antibody specific for tyrosine tubulin, most of the surface tubulin was also found to be tyrosinylated. For vimentin, an intermediate filament protein abundantly present in the cytoplasm of U937 cells, no staining could be detected. Confirmation of the flow cytometry data for surface actin and tubulin on unstimulated U937 cells was achieved by direct vesualization using a confocal laser scanning microscope. When U937 cells were activated with PMA and LPS, a marked reduction in the level of cell surface actin and tubulin occurred. The role of cell surface actin and tubulin on unstimulated U937 cells, in terms of monocyte function, remains to be elucidated. PMID- 1865115 TI - Conjugate formation in urea: coupling of insoluble peptides to alkaline phosphatase for ELISA and in situ detection of antibody-forming cells. AB - We report here a new method to produce synthetic peptide/alkaline phosphatase (AP) conjugates in the presence of urea. The method allows the use of peptides that are not soluble to a sufficient degree in aqueous buffers. The presence of 8 M urea during the construction of the synthetic peptide/AP conjugates does not influence enzyme activity nor the affinity of the anti-peptide antibodies for the conjugated peptide. We demonstrate that these synthetic peptide/AP conjugates can be used for detection of specific antipeptide antibody-forming cells (AFC) in vivo. This method for constructing enzyme conjugates with insoluble proteins or peptides suggest not only new possibilities for detection of specific AFC in vivo but also for applications in receptor-ligand studies, ELISA (enzyme-linked immunosorbent assay), and spot ELISA for detection of antibody-secreting cells in vitro. PMID- 1865116 TI - Assays for transforming growth factor beta. PMID- 1865117 TI - Freezing of cells--replacement of serum by oxypolygelatine. AB - A commercially available plasma expander (Gelifundol) containing 5.5% oxypolygelatine in buffered saline was used instead of serum as a supplement for freezing several types of human cell and a mouse myeloma cell line in liquid nitrogen. Viability, recovery, proliferation and cytotoxic activity were compared after freezing with a plasma expander and after conventional freezing with human AB serum or fetal calf serum. The plasma expander proved to be equivalent or superior to AB serum by all parameters tested and acceptable even when compared with fetal calf serum. Furthermore, this preparation is cheap, sterile, free of BSE, viral and mycoplasmal contamination or antibodies and foreign serum proteins. We therefore recommend it for freezing of cells for culture of HLA typing. PMID- 1865118 TI - A rapid and simple method for the preparation of a monospecific antibody to ovine haptoglobin. AB - Antisera specific to ovine haptoglobin were obtained by the immunization of rabbits with their own insolubilized haemoglobin after it had been allowed to react with a pool of haptoglobin-rich ovine serum. This method exploits the unique property of haptoglobin to bind with great specificity and affinity to both homologous and heterologous haemoglobin. The procedure is rapid, simple, inexpensive and could be readily applied to the production of antisera against the haptoglobins of other species. PMID- 1865119 TI - Production of monoclonal antibody against granulomonopoietic enhancing activity (GM-EA). AB - The granulomonopoietic enhancing activity (GM-EA) is a novel myelopoietic synergizing factor which acts as an enhancing factor for the proliferation and/or maturation of myelopoietic progenitor cells (CFU-GM) in combination with various types of colony-stimulating factors. In the present study, we report the production of a mouse anti-human GM-EA monoclonal antibody (mAb) designated 63A which is of the IgG1 subclass and has kappa light chains. This mAb can be used to quantitate GM-EA using a solid-phase enzyme-linked immunoabsorbent assay (ELISA) and is shown to have no cross-reaction with other myeloid synergizing factors. Furthermore, 63A mAb can significantly neutralize the colony-enhancing activity of GM-EA when added to CFU-GM assay cultures. In addition to being a convenient tool for the assay of GM-EA, 63A mAb may also be valuable for the exploration of the full potential of this enhancing factor in myelopoiesis. PMID- 1865120 TI - Cell mediated cytotoxicity against U 937 cells by human monocytes and macrophages in a modified colorimetric MTT assay. A methodological study. AB - The colorimetric MTT assay based on the selective ability of living cells to reduce 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide into formazan was adapted for measuring antibody independent monocyte mediated cytotoxicity. In view of the suggested application of adoptive immunotherapy we studied the anti leukaemic effects of activated human monocytes and macrophages against U 937 cells in vitro. Purified monocytes (greater than 98%) isolated by centrifugal elutriation and activated with interferon-gamma (IFN) were incubated with U 937 cells for 24 h at effector-to-target cell ratios (E/T) of 0.1-10. We assayed cytotoxicity by relating the optical density (OD) of residual metabolically active U 937 cells after exposure to effector cells to the OD of the initially inoculated U 937 cells. MTT reduction of effector cells was dependent on monocyte activation and differentiation into macrophages but did not interfere with the target cell signal up to an E/T ratio of 10. Improved signals could be obtained by dissolving formazan in DMSO with the addition of glycine instead of using propanol as solvent. Maximum cytostasis (95%, conventional [3H] incorporation assay) and cytotoxicity (80%, modified MTT assay) was reached with IFN activated monocytes at an E/T ratio of 10. In conclusion these data show that the modified MTT assay is a useful method of measuring monocyte mediated cytotoxicity in a sensitive, rapid, semi-automatic manner without the use of radioactive isotopes. PMID- 1865121 TI - A versatile dot-ELISA method with femtomole sensitivity for detecting small peptides. AB - Several protocols for conjugating peptides in situ to a protein carrier on paper, nitrocellulose, or nylon membranes were explored for their usefulness in dot ELISA detection of the peptides. The most sensitive method in which peptide diluted in bovine serum albumin is applied to nitrocellulose, then fixed with glutaraldehyde, can detect several peptides, ranging from 4 to 38 amino acids in length, at the level of 2-10 fmol. Both immunohistochemical grade antisera and monoclonal antibodies have been used successfully. The method may be a useful alternative to radioimmunoassay since there is no requirement for radiolabelled peptide, or (for quantitation) for known quantities of unlabelled peptide. The method has been used to monitor, semiquantitatively, the fractionation of FMRFamide-like or CCK-like peptides from the nematode Ascaris, and to detect peptide-like immunoreactivities in tissue extracts. PMID- 1865122 TI - Methods for the detection of anti-endothelial antibodies by enzyme-linked immunosorbent assay. AB - In order to obtain a routine simple screening test for the detection of anti endothelial antibodies (AEA) we developed a highly reproducible and sensitive enzyme-linked immunosorbent assay (ELISA) on fixed endothelial hybridoma cells. Detection of AEA with this type of monolayer appeared to be superior to ELISAs with monolayers of human umbilical vein endothelial cells, unfixed endothelial hybridoma cells or assays with membranes of endothelial cells. Glutaraldehyde treated endothelial hybridoma cells are most appropriate for use in ELISA procedures to detect AEA because the endothelial hybridoma cells are easy to culture, form a constant antigenic source and when plated and fixed to microtitre plates they can be stored without losing their ability to bind AEA. PMID- 1865123 TI - Efficient gene transfer and expression in primary B lymphocytes. AB - In this study we have used a panel of vectors expressing the chloramphenicol acetyltransferase (CAT) reporter gene under the control of different regulatory elements to optimize gene transfer and expression in primary B lymphocytes. The Moloney murine leukemia virus long terminal repeat (MoMLV LTR) and the SV40 early region promoters, while functional in transfected plasmacytoma cell lines, did not give rise to detectable CAT activity following transfection into primary activated mouse or human B lymphocytes. In contrast, the human cytomegalovirus immediate-early (HCMV-IE) enhancer/promoter functioned in both established and primary B cells. The highest expression levels in the primary cells were obtained with vectors containing the Adenovirus 2 major late promoter or the HCMV-IE enhancer/promoter in combination with the Adenovirus 2 tripartite leader and VA genes. These latter expression cassettes were placed in a retroviral vector with the aim of combining their capacity for high-level gene expression with the efficient stable gene transfer afforded by retroviral infection. Several retroviral constructs were made, some of which were able to generate high virus titers. However all of these underwent deletions during the process of retroviral infection, as judged by Southern analysis of infected cells, indicating that they were not optimal gene transfer vectors. The HCMV enhancer/promoter, which was the most active of the other expression cassettes tested in the primary B cells, was inserted into a retroviral vector which also expressed the hph gene under the transcriptional control of the retroviral LTR. This vector did not undergo rearrangement during the process of retroviral infection, as judged by Southern analysis. The CAT gene was inserted downstream of the HCMV promoter in this vector, and a high-titer retroviral stock was generated. Primary B lymphocytes infected with this vector gave high levels of CAT activity, under conditions in which parallel experiments with the hph drug resistance marker showed that one in 20 of the cells were infected. These experiments demonstrate efficient gene transfer and expression in primary B lymphocytes in vitro. PMID- 1865124 TI - Mannan-binding protein in human liver. AB - Mannan-binding protein (MBP) is a Ca(2+)-dependent lectin which was first described in 1978 in rabbit liver, and subsequently in serum and liver tissue from humans and a range of animal species. MBP structurally resembles C1q, and may act both as a focus for complement activation on the surface of microorganisms and as an opsonin in its own right. Low serum levels of serum MBP have been described in a group of children known to suffer from severe recurrent infections. MBP has also been reported to behave as an acute phase reactant. This preliminary study has investigated the localisation of MBP in human tissues using material obtained both at post mortem and from diagnostic liver biopsies. Using the IgG fraction of rabbit anti-human MBP, immunoperoxidase staining showed no evidence of significant MBP in a wide range of normal tissues, including liver taken both at post mortem and needle biopsy. However, there was a significant degree of staining for MBP in liver biopsies showing a variety of different pathologies, in particular severely damaged alcoholic livers, and those harbouring metastatic tumour. Moderate degrees of staining were also seen in liver biopsies from patients suffering from chronic biliary disease. It is uncertain whether this localisation of MBP in abnormal liver is an acute phase response, or represents a more fundamental link with liver disease. This question could be the focus for future studies. PMID- 1865125 TI - Production, characterisation and use of monoclonal antibodies to human interleukin-5 in an enzyme-linked immunosorbent assay. AB - Two mouse monoclonal antibodies (Mabs) against recombinant human interleukin 5(rhIL-5) have been produced, characterised and purified. Both are IgG1 antibodies and neutralised the activity of rhIL-5 in the B13 assay. Neither Mab cross-reacted with mouse IL-5. A two-site sandwich enzyme-linked immunosorbent assay (ELISA) was developed with different combinations of the mouse Mabs and also a rat anti-mouse IL-5 Mab, TRFK5, which also has activity against rhIL-5. The most sensitive assay, with a lower detection limit of 0.5 ng/ml IL-5, used TRFK5 as the capture antibody and the mouse anti-human IL-5 Mab as second antibody. The sensitivity of this assay was increased by an enhanced chemiluminescent reagent and resulted in a lower limit of detection around 40 pg/ml IL-5. PMID- 1865126 TI - Eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN). Detection by enzyme linked immunosorbent assay and purification from normal human urine. AB - Eosinophil protein X/eosinophil derived neurotoxin (EPX/EDN) is one of the cationic proteins found in the granules of the human eosinophilic granulocytes. EPX was purified from extracts of granules isolated from blood buffy coat cells of healthy donors. Polyclonal anti-EPX antibodies were subsequently raised in rabbits. The anti-EPX-antibodies raised in rabbits showed no reactivity with other proteins in the granule extract. The sandwich ELISA utilized the biotin/avidin amplification system and measured EPX over the range of 60-2000 pg/ml. The intra- and interassay coefficients of variation were 6.5% and 8.2%, respectively, and the mean recoveries of 25 and 50 pg of purified EPX added to diluted serum samples were 106 +/- 16% (mean +/- SD; n = 12) and 112 +/- 14%, respectively. Using this assay we found high amounts of EPX in normal human urine (U-EPX). U-EPX was purified by a two step procedure involving affinity chromatography on heparin Sepharose and size exclusion chromatography on Sephadex G-50 superfine. Extracted EPX and U-EPX had ribonuclease activity and comigrated on agarose electrophoresis. They also showed immunological identity when evaluated with rabbit anti-EPX antibodies, but they differed slightly on SDS-PAGE probably due to differences in glycosylation. Our results support the findings that EPX/EDN is identical to a nonsecretory ribonuclease isolated from urine. PMID- 1865127 TI - [Structure and function of platelet-derived endothelial cell growth factor]. PMID- 1865128 TI - [The sec genes of Escherichia coli]. PMID- 1865129 TI - Functional role of CD44 (Pgp-1) on activated B cells. PMID- 1865130 TI - Molecular genetics, structure, and function of C-reactive protein. PMID- 1865131 TI - Peptide presentation by class-I major histocompatibility complex molecules. AB - MHC class-I molecules express distinct peptide-binding pockets within their antigen-binding groove. These are critically involved in the binding of antigenic peptides. The amino acid composition of a pocket dictates the structure of a peptide which can be bound in it. This is evident as a consensus amino acid motif which has to exist within a peptide in order for it to bind to a particular MHC allele. Perturbation of a MHC pocket by amino acid substitution can result in the abolition of peptide binding. Less drastic mutations of the peptide-binding groove, particularly the ones away from the critical pocket, can subtly alter the conformation of bound peptide. Both types of substitution exert an influence on the TCR recognition of antigenic peptide. Peptides are also critically involved in the positive selection of the class-I-restricted TCR repertoire in the thymus. These self peptides act by mimicking their foreign antigens. This mimicking involves the binding of self peptides and foreign antigenic peptides to the same pockets of the MHC class-I-antigen binding groove. Consequently, MHC class-I polymorphism in the antigen binding groove controls the intrathymic positive selection and peripheral antigen presentation by the same mechanisms. The majority of positively selecting self peptides could well originate from the extracellular processing of circulating self proteins. Using the diverse, extracellularly generated self peptides and the different determinant density requirements for positive versus negative selection, the immune system can ensure the repertoire diversity, avoiding both the massive clonal deletion of the selected repertoire and the autoreactivity of its T cells. PMID- 1865134 TI - [Bed-side approach to water and electrolyte metabolism disorders]. PMID- 1865133 TI - Direct tolerance induction in mature B lymphocytes may resemble clonal anergy phenomenon. AB - Several mechanisms have been postulated for direct induction of B-cell tolerance in mature B cells, such as the Bretscher and Cohn [5] hypothesis which states that an antigenic signal to B cells without the 'second signal' provided by T cells or lymphokines produces unresponsiveness. A second explanation is that tolerogens which cross-link immunoglobulin and Fc receptors abort the biochemical activation of the B cell via the phosphatidyl inositol pathway. Results of our studies are not consistent with either of these hypotheses. We speculated that DNP-MGG induces immunoglobulin receptor capping and internalization in mature B cells, but a suppressive signal is given to the B cell when DNP-MGG is present at the time of antigen receptor reexpression in a fashion similar to clonal anergy. The studies reported here test this hypothesis as a possible additional mechanism of direct B-cell tolerance. When pure DNP-specific B cells were incubated for 6 h with DNP-MGG in the presence of lymphokine-rich EL-4 supernatant, an immune response was induced; but 48 h preincubation with DNP-MGG in the presence of lymphokines induced tolerance. If B-cell cultures were preincubated with DNP-MGG for 6 h followed by a 24-hour incubation without conjugate and DNP-MGG was then added for the third preincubation period of 18 h (at a time when receptors are being reexpressed), tolerance was induced. Substitution of DNP-Ficoll antigen for DNP-MGG in either the first or third time period did not result in tolerance induction but substituting DNP-KLH during either of these two periods did result in tolerance. PMID- 1865135 TI - [Hypernatremia and hyponatremia]. PMID- 1865132 TI - Heat shock proteins and immune responses: an early view. PMID- 1865136 TI - [Diagnosis and therapy of water metabolism disorders]. PMID- 1865137 TI - [Hyperkalemia and hypokalemia]. PMID- 1865138 TI - [Hypercalcemia and hypocalcemia]. PMID- 1865139 TI - [Hypophosphatemia and hyperphosphatemia]. PMID- 1865140 TI - [Magnesium metabolism disorders]. PMID- 1865141 TI - [Metabolic disorders of trace elements]. PMID- 1865142 TI - [Adverse effect of various drugs on electrolyte metabolism]. PMID- 1865143 TI - [Necessary knowledge for understanding of acid-base equilibrium]. PMID- 1865144 TI - [Diagnosis and classification of renal tubular acidosis]. PMID- 1865145 TI - [Cautions for administration of diuretics in the therapy of water-electrolyte imbalance]. PMID- 1865146 TI - [Diagnosis and therapy of water-electrolyte imbalance]. PMID- 1865147 TI - [Three cases of anti-phospholipid antibody syndrome due to SLE]. PMID- 1865148 TI - [A case of chondrosarcoma of femur forming tumor embolism in the left heart atrium]. PMID- 1865149 TI - [A case of IGA nephropathy complicated with membranous nephropathy]. PMID- 1865150 TI - [A case of Basedow's disease with thiamazole and propylthiouracil-induced thrombocytopenia]. PMID- 1865151 TI - [Multiple organ failure during digestive disease surgery]. PMID- 1865152 TI - [Tumor-related genes]. PMID- 1865153 TI - Correlative light and electron microscopic observations on ectopic neurons in the cerebellum of dreher mutant mouse. AB - The structure of ectopic neurons in the cerebellum of dreher mutant mouse was investigated by correlative light and electron microscopic observations. Tissue blocks were fixed in buffered aldehyde and embedded in a mixture of 2 hydroxypropyl methacrylate, Quetol 523, and methyl methacrylate. Sections at 0.4 0.5 microns in thickness were examined by electron microscopy after observation under a light microscope. By comparing the electron images with those of light microscopy in the same sites, the structures of ectopic cells were confirmed. Ectopic Purkinje cells were arranged with cell bodies that contained an oval, spherical or wrinkled nucleus without deep invagination and the thin layers of endoplasmic reticulum at the perinuclear regions. Granule cells were ectopically matured in the external granular layer and within the cluster at the cortical region. This method provides a useful procedure for understanding structures of the cerebellar neurons of the mutant. PMID- 1865154 TI - Mineral content of the innermost enamel in erupted human teeth. AB - It has been said that the innermost enamel of erupted human teeth is either a hyper- or a hypomineralized layer. Using SEM-EDX, in the present study, the Ca and P mineral contents of the innermost 10-15 microns enamel showing a highly negative birefringence (IE-I) were analyzed and compared with those of the adjacent inner enamel (IE-II) in each cuspal-third, mid-coronal, and cervical third region. The Ca content in the IE-I zone was significantly lower than that in the IE-II zone in the mid-coronal and cervical-third regions, whereas the significant difference of P content was seen only in the cervical-third region. In the other areas, the IE-I zone tended to be lower than the IE-II zone. These significant and no significant differences of Ca and P contents may be due to the difference in the amount of organic substance in the IE-II zone of the three regions, and that of these mineralization rates after eruption of a tooth. PMID- 1865155 TI - Association of cytoskeletons with the Golgi apparatus: three-dimensional observation and computer-graphic reconstruction. AB - The association of cytoskeletons with the Golgi apparatus (GA) in cultured 3Y1 cells was investigated by stereo electron microscopy of thick sections and computer-graphic reconstruction of serial thin sections. The 3-dimensional analysis has demonstrated that: 1) both microtubules (MT) and vimentin intermediate filaments (IF) were abundantly present in close vicinity to GA, and some of them were closely associated with GA; and 2) such GA-associated cytoskeletons were attached to GA either at their termini or at their lateral side. The present observations suggest that both MT and vimentin IF are responsible for maintaining the structural integrity of GA. PMID- 1865156 TI - Venous microvasculature of the pineal body and choroid plexus in the rat. AB - Rats were perfused from aorta with Ringer's solution and with Karnovsky's fixative, and injected from the right atrium with Mercox resin. Specimens were properly taken, observed under LM, TEM, SEM, and stereo-photographed. Fenestrated endothelial cells of the pineal capillary were observed to contain plenty of microtubules running parallel to the long axis of the vessel. The endothelial basal lamina appeared anchored by microfibrils onto fine collagen fibrils and onto the basal lamina of the perivascular cells. These findings indicate resistance of the capillary endothelium against compression by perivascular hydrostatic pressure, and strongly suggest that the perivascular cerebrospinal fluid is absorbed into the capillary lumen. Resin cast of the pineal venous system looked like a glomerule with two longer collecting veins on the ventral surface and with shorter ones on the dorsal side all emptying into the straight sinus and the confluence of sinuses. Resin cast of the choroid plexus venous system tended to lobulate and looked like a vine with a spiral collecting vein emptying into the great vein. Two veins were found connecting the great vein to the confluence and to the transverse sinuses. These could be effective collaterals in case of occlusion of Galen's vein. PMID- 1865157 TI - The three-dimensional structure of the clear zone of a cultured osteoclast. AB - Osteoclasts collected from long bones of newborn mice were cultured on dentine slices. Then, osteoclasts were sectioned by alternating semithin and ultrathin sections, and the three-dimensional reconstruction was made by the serial semithin sections. By this method, the present study showed first the three dimensional structure of an osteoclast, especially the clear zone. A reconstructed osteoclast with complicated contours shifted from the lacuna, and its clear zone was a ring-shaped structure. By TEM, a new small lacuna was formed under the ruffled border, and the clear zone could be further classified into three types. The present study suggested that the synthetic observations of both three-dimensional structure and ultrastructure by transmission electron microscopy were necessary to determine whether the osteoclast was resorbing or migrating. According to these observations, the reconstructed osteoclast seemed to be migrating. PMID- 1865158 TI - Three-dimensional reconstruction of goblet cells in the rabbit conjunctivum. AB - Goblet cells in the rabbit bulbar conjunctivum were not real "goblet," but were variable in shape. The diversity of the morphology became evident by means of computer-aided three-dimensional reconstruction. All of the cells reconstructed (N = 5) were in touch with the basal lamina, and were open to the epithelial surface. Their cytoplasm was filled with secretory granules (about 71% of the cellular volume, in average), while the nucleus occupied only 5.3%. PMID- 1865159 TI - Intensified conventional insulin treatment retards the microvascular complications of insulin-dependent diabetes mellitus (IDDM): the Stockholm Diabetes Intervention Study (SDIS) after 5 years. AB - Ninety-six patients with insulin-dependent diabetes mellitus (IDDM) and non proliferative retinopathy were randomized to intensified conventional treatment (ICT) (n = 44) or regular treatment (RT) (n = 52), and followed up for 5 years. HbA1c decreased from 9.5 +/- 0.2% (mean value +/- SEM) to 7.2 +/- 0.1% in the ICT group, and from 9.4 +/- 0.2% to 8.7 +/- 0.1% in the RT group (difference between the groups, P less than 0.001). Retinopathy increased in both groups (P less than 0.001), but after 5 years it was worse in the RT group (P less than 0.05). The urinary albumin excretion rate was higher in the RT group than in the ICT group after 5 years (239.9 +/- 129.7 micrograms min-1 vs. 46.0 +/- 26.1 micrograms min 1, P less than 0.05). Eight RT patients developed manifest nephropathy, compared with none in the ICT group (P less than 0.01). After 5 years the conduction velocities of the sural (P less than 0.05), peroneal (P less than 0.01) and tibial (P less than 0.001) nerves were lower in the RT group. The respiratory sinus arrhythmia was 12.1 +/- 1.2 beats min-1 in the RT group and 16.7 +/- 1.4 beats min-1 in the ICT group at the end of the study (P less than 0.01). The increases in retinopathy (P less than 0.01), nephropathy (P less than 0.01) and neuropathy (P less than 0.001) were all related to the mean HbA1c value during the study. Smoking habits only influenced the progression of retinopathy (P less than 0.05). Serious hypoglycaemia occurred in 34 ICT patients and 29 RT patients (242 and 98 episodes, respectively) (P less than 0.05). Whereas weight was stable in the RT group, the body mass index increased by 5.8% in the ICT group (P less than 0.01). In conclusion, microvascular complications of diabetes were retarded by intensified conventional insulin treatment. However, such treatment increased the frequency of serious hypoglycaemia, and led to an increase in body weight. PMID- 1865160 TI - Thalassaemia trait and myocardial infarction: low infarction incidence in male subjects confirmed. AB - A total of 4401 subjects admitted to the Medical Division of St Camillo Hospital in Comacchio (Ferrara, Italy) over a period of 7 years were prospectively evaluated in order to determine whether the heterozygous beta-thalassaemic (HBT) could be considered as a protective factor against the occurrence of acute myocardial infarction (AMI). Of the total patient sample, 3954 subjects were non beta-thalasaemics (NBTs), and 447 subjects were heterozygous beta-thalassaemics (HBTs). AMI was diagnosed in 384 patients, of whom 17 individuals were HBTs and 367 subjects were NBTs. The prevalence of HBTs in this group was significantly lower than expected (4.43%, P less than 0.0001). Furthermore, an analysis by sex showed that this lower prevalence could be attributed to male patients. Moreover, only in male subjects was a significant negative correlation observed between AMI and HBT. The mean age at which AMI occurred in male HBTs was significantly higher than in male NBTs (72 +/- 2.69 vs. 63 +/- 0.7 years, P less than 0.05), while no differences were found in the mean age at which AMI occurred between HBT and NBT female subjects. This study demonstrates that the thalassaemic trait may afford some protection against the occurrence of AMI in men. PMID- 1865161 TI - Sinemet (CR4): an open-label study in moderately severe Parkinson's disease. AB - Almost all patients with idiopathic Parkinson's disease respond to levodopa and progress steadily, requiring an increased overall dosage with time. Sinemet CR4 offers a theoretically attractive method of achieving gradual sustained release of levodopa over time which may be more physiological to striatal dopamine receptors in the early stages of the disease. This study evaluated 20 patients with moderate to severe Parkinson's disease who were treated with Sinemet CR4 over a 1-year period. Eleven patients completed the full year on therapy, and nine subjects withdrew. Of the withdrawals, two subjects died from non Parkinson's disease-related illness, three showed no therapeutic benefit, and four responded well for a minimal 6-month period, but then lost therapeutic benefit and developed more severe dystonias. A higher overall levodopa dosage was required by all patients, and side-effects of levodopa were still present in most patients. However, the nocturnal benefit of this long-acting preparation was observed by all the patients in the study. Slow onset of action of Sinemet CR4 resulted in early-morning immobility. Sinemet CR4 cannot replace standard Sinemet, but appears to be a useful form of adjunct therapy in selected patients. PMID- 1865162 TI - Excess mortality in giant cell arteritis. AB - A 13-year departmental sample of 34 patients with definite (biopsy-verified) giant cell arteritis (GCA) was reviewed. The mortality of this material was compared to sex-, age- and time-specific death rates in the Danish population. The standardized mortality ratio (SMR) was 1.8 (95% confidence limits, 1.1-2.8). During the same period 146 patients with probable (not biopsied, but clinically diagnosed in the department) GCA and 85 cases of possible (diagnosed and treated before admission) GCA had been admitted to the department. Those two groups did not differ from the biopsy-verified group with respect to SMR, sex distribution or age. In the group of patients with department-diagnosed GCA (definite + probable = 180 patients), the 95% confidence interval for the SMR of the women included 1.0. In all other subgroups there was a significant excess mortality. Excess mortality has been found in two of seven previous studies on survival in GCA. The prevailing opinion that steroid-treated GCA does not affect the life expectancy of patients is probably not correct. PMID- 1865163 TI - Obstructive sleep apnoea syndrome in morbidly obese patients. AB - Twenty-seven morbidly obese patients (13 men and 14 women) with body mass index greater than or equal to 40 kg m-2 were examined. The mean age of the subjects was 36.9 +/- 8.2 years (range 23-51 years), and the mean BMI was 50.2 +/- 6.2 kg m-2 (range 40.0-62.9 kg m-2). A whole-night sleep recording was made for all patients with signs or symptoms indicative of possible obstructive sleep apnoea syndrome (OSAS). If the first nocturnal sleep recording was abnormal, it was controlled after 1 year. Eleven (10 men and one woman) of the 27 patients had an oxygen desaturation index (ODI) of 10 h-1. They were symptomatic with excessive daytime sleepiness or other daytime symptoms of OSAS. The occurrence of OSAS in men and women was 76.9 and 7.1%, respectively. Arterial hypertension was associated with OSAS, but not with smoking or the degree of obesity. Antihypertensive treatment was received by nine of the 27 patients; six of them had OSAS. Thus six of the 11 (54.5%) patients with OSAS and three of the 16 (18.8%) nonapnoeic patients were treated for arterial hypertension (Fisher exact test, P = 0.042). The odds ratio of OSAS for arterial hypertension is 5.2 (95% CI, 0.71-43.6). Vertical-banded gastroplasty was performed in 14 patients, three of whom had OSAS. The selection of patients for gastroplasty was made without taking into account the results of sleep recordings. In the three OSAS patients, a 30-38% reduction in BMI was achieved by surgery. Eight patients with OSAS were treated with an intensified dietary regimen, and the reduction in BMI ranged from -2.6 to 33%. OSAS was either cured or significantly improved in six (55%) patients, with a mean reduction in BMI of 27%, while in patients with persistent OSAS the mean reduction in BMI was only 7%. PMID- 1865164 TI - Serum lipid and apolipoprotein levels in non-hypertensive lean NIDDM patients. AB - To determine the possible role of a glycaemic control in lipid metabolism in non insulin-dependent diabetes mellitus (NIDDM) patients, serum lipid and apolipoprotein levels were measured in well-controlled and poorly controlled lean NIDDM without proteinuria and hypertension. A sample of 96 lean NIDDM patients (body mass index less than 25 kg m-2 in men and less than 27 kg m-2 in women) were divided into two groups: group I, where the HbA1c concentration had been less than 6% for the previous 3 months, and group II, where the HbA1c concentration had been greater than 8% for the previous 3 months. Serum total cholesterol, triglyceride, and HDL-cholesterol levels showed no significant differences between groups I and II. Furthermore, serum levels of apolipoproteins AI, AII, B, CII, CIII, and E did not differ significantly between groups I and II. These results suggest that glycaemic control did not influence lipid metabolism in lean NIDDM patients. PMID- 1865165 TI - The sleep apnoea syndrome in obesity: risk of sudden death. AB - A total of 34 severely obese men with a history of heavy snoring and excessive daytime sleepiness indicative of obstructive sleep apnoea syndrome (OSAS) were studied prospectively. Their mean age was 46 years, and mean body mass index was 41.6 kg m-2. During a 4-year follow-up, 15% (5/34) of these subjects died (three cases of acute myocardial infarction and two cases of pulmonary oedema), all of them suddenly and unexpectedly, outside hospital. On autopsy the degree of atherosclerosis was found to be moderate in all cases. In 68% (15/22) of the men a pathological apnoea index (mean value 46 +/- 20) confirmed the OSAS diagnosis. Exercise tests and neurological examinations did not reveal any other causes of daytime sleepiness. Mean blood pressure at rest and during exercise was normal, and mean serum lipid and blood glucose levels were normal. Spirometry revealed intrapulmonary restrictive changes that could not be attributed to the heavy thoracic wall. Compliance was reduced to about 50% of reference values, and the mean pCO2 level (5.8 kPa) was close to the upper reference limit. Blood tests suggested that high alcohol consumption may be an important factor contributing to OSAS. These results demonstrate that morbidly obese men with a history of OSAS have a high risk of sudden cardiovascular death, despite the absence of other conventional risk factors. PMID- 1865166 TI - Increased occurrence of arrhythmias in men with ischaemic type ST-segment depression during long-term ECG recording. Prognostic impact on ischaemic heart disease: results from the prospective population study 'Men born in 1914', Malmo, Sweden. AB - The objective of this long-term ECG (LTER) study in 394 68-year-old men, selected at random from the general population of Malmo, Sweden, was to determine the prevalence and occurrence of cardiac arrhythmias and their impact on morbidity and mortality from IHD. According to Lown classification, 29.4% (116 men) had ventricular arrhythmia (VA) group 4-5. Serious ventricular arrhythmia (Lown group 4-5) was more common in men with asymptomatic ischaemic type ST-segment depression (STD) than in those without it (37.8% vs. 26.7%: P less than 0.05). During the mean follow-up period of 53.1 months there were seven IHD deaths (6%) among the 116 patients with VA, Lown 4-5, and nine IHD deaths (3.2%) among the 278 patients without serious VA, Lown 0-3, (P = 0.26). Six and three of these deaths, respectively, were considered to be sudden (P = 0.022). The increased cardiac event rate (fatal or non-fatal MI or deaths due to chronic IHD) associated with a serious ventricular arrhythmia disappeared when history of IHD at baseline and occurrence of STD during LTER were taken into account. The study did not provide any evidence to suggest that ventricular arrhythmia was triggered by myocardial ischaemia. Five of 9 (56%) deaths due to IHD in men with STD occurred among the 38% (37/98) of patients who belonged to Lown class 4-5. It is concluded that the prognostic information derived from LTER can be improved by combined monitoring of STD and ventricular arrhythmias. PMID- 1865167 TI - Long-term effects of simvastatin in familial dysbetalipoproteinaemia. AB - The long-term effects (66 weeks) of simvastatin (40 mg in one or two doses per day), an inhibitor of HMG CoA-reductase, were evaluated in 12 patients with familial dysbetalipoproteinaemia (type III hyperlipoproteinaemia). Simvastatin had a persistent hypolipidaemic effect; the mean reduction in serum cholesterol was 36-51%, and the mean reduction in serum triglycerides was 32-55%. The decrease in serum lipids was caused by a decline in VLDL-cholesterol and LDL cholesterol levels; the mean ratio between VLDL-cholesterol and serum triglycerides decreased significantly from 1.06 to 0.73. There was no significant difference between the once-a-day and twice-a-day regimens. Simvastatin was well tolerated; no serious side-effects were observed. These data demonstrate the usefulness of simvastatin in the therapy of familial dysbetalipoproteinaemia. PMID- 1865168 TI - Evaluation of a structured treatment and teaching programme on asthma. AB - The objective of this study was to evaluate a structured treatment and teaching programme for adult patients with moderate to severe asthma. The design consisted of a prospective, before-after trial: the same consecutive patients were studied before and after intervention with observation periods 1 year before and 1 year after intervention. The investigation took place within a tertiary care centre (university hospital). A total of 142 consecutive patients were referred for in patient treatment of their asthma, of whom 132 (93%) patients participated in the follow-up examination. The intervention consisted of a structured 5-d in-patient treatment and teaching programme presented by a specialized nurse educator. The aim of the programme was for the patient to assume greater responsibility for disease management, including self-monitoring of peak expiratory flow and qualified self-adaptation of drug therapy. The main outcome measures were the frequency of severe asthma attacks, hospitalization, and absenteeism from work (data provided by health insurance companies), patients' compliance and management skills. During the year before and the year after the intervention 71% and 36%, respectively of patients had one or more severe asthma attacks (mean difference 35%, 95% CI: 25-45%, P less than 0.0001). The percentage of patients who were hospitalized because of asthma decreased from 39% to 22% (mean difference 17%, 95% CI: 7-27%, P less than 0.002). The percentage of employed patients (n = 67) who were absent from work because of asthma decreased from 60% to 43% (mean difference 17%, 95% CI: 4-30%, P less than 0.04). The patients' adherence to maintenance drug therapy and their management skills improved significantly. It was concluded that the participation of patients with moderate to severe asthma in a structured treatment and teaching programme resulted in a substantial reduction in asthma morbidity in the year following the intervention. PMID- 1865169 TI - Successful treatment of hepatosplenic candidiasis with a liposomal amphotericin B preparation. AB - The case of a granulocytopenic patient with acute undifferentiated leukaemia and hepatosplenic candidiasis who was refractory to conventional deoxycholate amphotericin B (AmpB) and 5-flucytosine therapy is reported. He experienced severe AmpB-related side-effects, and was subsequently successfully treated with a pharmaceutical preparation of AmpB (5.7 g) entrapped in sonicated liposomes, composed of lecithin, cholesterol and stearylamine in a molar ratio of 4:3:1. Three months later, during maintenance chemotherapy, liposomal AmpB (5.1 g) was reinstituted due to the finding of biopsies positive for Candida albicans at bronchoscopy. After healing of the patient's fungal infection a left upper lobe resection was performed, which showed advanced fibrosis with signs of inflammation, but no evidence of fungal disease. Since no acute side-effects and only moderate hypokalaemia were observed, it appears that liposomal AmpB is superior to conventional AmpB treatment in granulocytopenic patients with hepatosplenic candidiasis and unbearable therapy-related side-effects. PMID- 1865170 TI - Adrenocortical insufficiency with normal serum cortisol levels and hyporeninaemia in a patient with acquired immunodeficiency syndrome (AIDS). AB - The acquired immunodeficiency syndrome (AIDS) has been associated with abnormalities of adrenocortical function, and hypoaldosteronism due to hyporeninaemic hypoaldosteronism (HHA). We here report the case of a woman with AIDS associated with orthostatic hypotension, persistent hyponatraemia and hyperkalaemia, in whom basal serum cortisol levels were normal and serum renin activity was low. Subsequent post-mortem examination revealed almost complete adrenocortical destruction. A possible explanation of this apparently contradictory combination of findings is discussed, together with the therapeutic implications for similar cases. PMID- 1865171 TI - Expression of type III hyperlipoproteinaemia in a subject with secondary hypothyroidism bearing the apolipoprotein E2/2 phenotype. AB - Post-surgical hypothyroidism developed in a now 43-year-old woman with complete insufficiency of the anterior pituitary gland who discontinued levothyroxine replacement therapy. Serum cholesterol and serum triglyceride levels increased in parallel, and classical type III hyperlipoproteinaemia (HLP) with xanthoma striata palmaris developed. The patient is homozygous for apolipoprotein (apo) E2. The case reported here represents the first example of manifestation of type III hyperlipoproteinaemia in a subject with secondary hypothyroidism bearing the apo E2/2 phenotype. PMID- 1865173 TI - Internal medicine and molecular biology--molecular medicine. PMID- 1865172 TI - Nephrocalcinosis in Sjogren's syndrome: a late sequela of renal tubular acidosis. AB - Sjogren's syndrome (SS) is an autoimmune exocrinopathy that develops into systemic autoimmune disease in 25% of patients, leading to general complications, one of which is kidney involvement. It presents mainly as interstitial nephritis, disclosed by hyposthenuria, distal renal tubular acidosis (RTA) and diabetes insipidus. We here describe five cases of SS with type-1 RTA (hyperchloraemic metabolic acidosis with an anion gap and alkaline urine pH) who developed nephrolithiasis, nephrocalcinosis and renal insufficiency. Hypercalciuria due to acidosis was the main nephrocalcinosis-prone factor in four patients; four subjects displayed diminished renal concentrating capacity, and two had hypokalaemia. PMID- 1865174 TI - Properties of transient K+ currents and underlying single K+ channels in rat olfactory receptor neurons. AB - The transient potassium current, IK(t), of enzymatically dissociated rat olfactory receptor neurons was studied using patch-clamp techniques. Upon depolarization from negative holding potentials, IK(t) activated rapidly and then inactivated with a time course described by the sum of two exponential components with time constants of 22.4 and 143 ms. Single-channel analysis revealed a further small component with a time constant of several seconds. Steady-state inactivation was complete at -20 mV and completely removed at -80 mV (midpoint 45 mV). Activation was significant at -40 mV and appeared to reach a maximum conductance at +40 mV (midpoint -13 mV). Deactivation was described by the sum of two voltage-dependent exponential components. Recovery from inactivation was extraordinarily slow (50 s at -100 mV) and the underlying processes appeared complex. IK(t) was reduced by 4-aminopyridine and tetraethylammonium applied externally. Increasing the external K+ concentration ([K+]o) from 5 to 25 mM partially removed IK(t) inactivation, usually without affecting activation kinetics. The elevated [K+]o also hyperpolarized the steady-state inactivation curve by 9 mV and significantly depolarized the voltage dependence of activation. Single transient K+ channels, with conductances of 17 and 26 pS, were observed in excised patches and often appeared to be localized into large clusters. These channels were similar to IK(t) in their kinetic, pharmacological, and voltage dependent properties and their inactivation was also subject to modulation by [K+]o. The properties of IK(t) imply a role in action potential repolarization and suggest it may also be important in modulating spike parameters during neuronal burst firing. A simple method is also presented to correct for errors in the measurement of whole-cell resistance (Ro) that can result when patch-clamping very small cells. The analysis revealed a mean corrected Ro of 26 G omega for these cells. PMID- 1865175 TI - The mechanism of KATP channel inhibition by ATP. PMID- 1865176 TI - Contraction threshold and the "hump" component of charge movement in frog skeletal muscle. AB - The delayed component of intramembranous charge movement (hump, I gamma) was studied around the contraction threshold in cut skeletal muscle fibers of the frog (Rana esculenta) in a single Vaseline-gap voltage clamp. Charges (Q) were computed as 50-ms integrals of the ON (QON) and OFF (QOFF) of the asymmetric currents after subtracting a baseline. The hump appeared in parallel with an excess of QON over QOFF by approximately 2.5 nC/mu F. Caffeine (0.75 mM) not only shifted the contraction threshold but moved both the hump and the difference between the ON and OFF charges to more negative membrane potentials. When using 10-mV voltage steps on top of different prepulse levels, the delayed component, if present, was more readily observable. The voltage dependences of the ON and OFF charges measured with these pulses were clearly different: QON had a maximum at or slightly above the contraction threshold, while QOFF increased monotonically in the voltage range examined. Caffeine (0.75 mM) shifted this voltage dependence of QON toward more negative membrane potentials, while that of QOFF was hardly influenced. These results show that the delayed component of intramembranous charge movement either is much slower during the OFF than during the ON, or returns to the OFF position during the pulse. Tetracaine (25 microM) had similar effects on the charge movement currents, shifting the voltage dependence on the ON charge in parallel with the contraction threshold, but to more positive membrane potentials, and leaving QOFF essentially unchanged. The direct difference between the charge movement measured in the presence of caffeine and in control solution was either biphasic or resembled the component isolated by tetracaine, suggesting a common site of caffeine and tetracaine action. The results can be understood if the released Ca plays a direct role in the generation of the hump, as proposed in the first paper of this series (Csernoch et al. 1991. J. Gen. Physiol. 97:845-884). PMID- 1865178 TI - Catabolite repression by galactose in overexpressed GAL4 strains of Saccharomyces cerevisiae. AB - Catabolite repression by galactose was investigated in several strains of Saccharomyces cerevisiae grown on different carbon sources. Galactose repressed as much as glucose; raffinose was less effective. Full derepression was achieved with lactate. The functions tested were L-lactate ferricytochrome c oxidoreductase, NAD-glutamate dehydrogenase, and respiration. Galactose repression was observed only in the GAL4 but not in the gal4 strain. The presence of multiple copies of the GAL4 gene enhanced the repression by galactose. Different alleles of the GAL4 gene and the copy number did not affect glucose repression. PMID- 1865177 TI - Characterization of two distinct depolarization-activated K+ currents in isolated adult rat ventricular myocytes. AB - Depolarization-activated outward K+ currents in isolated adult rat ventricular myocytes were characterized using the whole-cell variation of the patch-clamp recording technique. During brief depolarizations to potentials positive to -40 mV, Ca(2+)-independent outward K+ currents in these cells rise to a transient peak, followed by a slower decay to an apparent plateau. The analyses completed here reveal that the observed outward current waveforms result from the activation of two kinetically distinct voltage-dependent K+ currents: one that activates and inactivates rapidly, and one that activates and inactivates slowly, on membrane depolarization. These currents are referred to here as Ito (transient outward) and IK (delayed rectifier), respectively, because their properties are similar (although not identical) to these K+ current types in other cells. Although the voltage dependences of Ito and IK activation are similar, Ito activates approximately 10-fold and inactivates approximately 30-fold more rapidly than IK at all test potentials. In the composite current waveforms measured during brief depolarizations, therefore, the peak current predominantly reflects Ito, whereas IK is the primary determinant of the plateau. There are also marked differences in the voltage dependences of steady-state inactivation of these two K+ currents: IK undergoes steady-state inactivation at all potentials positive to -120 mV, and is 50% inactivated at -69 mV; Ito, in contrast, is insensitive to steady-state inactivation at membrane potentials negative to -50 mV. In addition, Ito recovers from steady-state inactivation faster than IK: at -90 mV, for example, approximately 70% recovery from the inactivation produced at -20 mV is observed within 20 ms for Ito; IK recovers approximately 25-fold more slowly. The pharmacological properties of Ito and IK are also distinct: 4-aminopyridine preferentially attenuates Ito, and tetraethylammonium suppresses predominantly IK. The voltage- and time-dependent properties of these currents are interpreted here in terms of a model in which Ito underlies the initial, rapid repolarization phase of the action potential (AP), and IK is responsible for the slower phase of AP repolarization back to the resting membrane potential, in adult rat ventricular myocytes. PMID- 1865180 TI - Ultrastructural localization of the Pasteurella multocida toxin in a toxin producing strain. AB - Toxigenic strains of Pasteurella multocida produce the 147 kDa protein Pasteurella multocida toxin (PMT) which is responsible for the osteoclastic bone resorption in progressive atrophic rhinitis in pigs and induces such resorption in all experimental animals tested so far. In the present study we have carried out immunocytochemistry on formaldehyde- and glutaraldehyde-fixed ultracryocut P. multocida using a pool of monoclonal antibodies against different epitopes on PMT as the first layer and affinity purified rabbit anti-mouse IgG as the second layer. Goat anti-rabbit IgG conjugated with 5 nm gold particles was used as marker. The gold particles were silver-enhanced prior to examination in the transmission electron microscope. Whole bacteria were also immunostained after fixation and critical point drying and examined by scanning transmission electron microscopy. The results showed that PMT was located in the cytoplasm of P. multocida. PMT could not be detected on intact, undamaged P. multocida by scanning electron microscopy. Neither pili nor flagella could be detected on the surface of the negatively stained P. multocida strains investigated. PMT has a series of characteristics encompassed in the definition of an exotoxin. However, that PMT was not secreted by living intact P. multocida is unexpected for an exotoxin. PMID- 1865179 TI - Cell wall glycoproteins of Candida albicans as released by different methods. AB - Different methods of extraction frequently used in other studies were used to release glycoproteins from both intact cells and isolated cell walls of yeast and hyphal forms of Candida albicans. Extracts were obtained from whole cells by treatment (i) with 2-mercaptoethanol (beta ME) at pH 8.6 and 37 C degrees and (ii) with zymolyase after treatment with beta ME. Extracts were obtained from isolated and washed cell walls (i) by boiling with beta ME and sodium dodecyl sulphate (SDS), (ii) by boiling with SDS and (iii) by treatment with zymolyase after SDS. The extracts were separated by SDS-polyacrylamide gel electrophoresis and analysed by Western blotting with four reagents. Analysis with concanavalin A (ConA) revealed different glycoprotein populations depending on the treatment. Three possible germ-tube-specific constituents were observed; and 80 kDa component released by beta ME from both intact cells and cell walls, and 47 kDa and 43 kDa moieties released by zymolyase only from intact cells. MAb 4C12, specific for the protein portion of a large germ tube constituent, recognized polydisperse material which just entered the gel in beta ME extracts and in the region extending up from 200 kDa to near the top of the gel in zymolyase extracts. MAb 24.17, specific for a carbohydrate determinant of yeast phase cells, reacted with disperse material in the region from the top of the gel to one-third to two-thirds the distance to the 220 kDa mass marker. Antiserum specific for the serotype A determinant of mannan reacted with large disperse component(s) migrating in the region from the top of the gel to about two-thirds the distance to the 220 kDa mass marker and with a 180 kDa component. The components recognized by MAb 4C12, but not those recognised by MAb 24.17 and serotype A antiserum, were effected by treatment with endo-beta-N acetylglucosamidase H. The various analyses revealed that the method of extraction affected the composition and size of the constituents recognized by the reagents. PMID- 1865181 TI - Tubular spinae are long-distance connectors between bacteria. AB - The marine pseudomonad D71 (NCMB 2018) ['Spinomonas maritima'] can be induced to produce long tubular surface appendages (spinae) in a growth medium of low osmolarity. In general, spina-carrying cells show these appendages with open distal ends. We examined cultured cells by scanning and transmission electron microscopy, using both critical-point drying and thin sectioning after embedding with agarose protection. By scanning electron microscopy, spinae were observed that connected cells over distances of several micrometers. Ultrathin sections often revealed an additional layer outside the outer membrane, resembling an S layer. The inner and outer cell membranes were often joined at spina-insertion areas. Furthermore, evidence was found in ultrathin sections for uninterrupted tubes connecting two cells over a distance of up to 7 microns. We propose, therefore, that spinae form the framework for wide open cell clusters; we hypothesize that these spinae might also permit an exchange of cell-to-cell signals. PMID- 1865182 TI - Isolation and purification of viable Ureaplasma urealyticum cells free from medium components. AB - A procedure was devised to produce Ureaplasma urealyticum preparations free of adsorbed components of the growth medium, which contains high concentrations of serum. The ureaplasmas were cultivated in a medium containing PPLO-serum fraction as a replacement for horse serum. High titres of ureaplasmas (greater than 10(7) c.f.u. ml-1) were obtained. Harvested cells were then purified by Urografin density gradient centrifugation. By use of 3H-labelled ureaplasma cells and 125I labelled medium components, a distinct band of viable cells devoid of serum constituents was demonstrated. The absence of medium components was verified by immunoblotting cells from this band with antiserum to medium components. Medium components that had been present before the purification procedure were undetectable in the purified cell fraction obtained. The viability of the purified ureaplasma cells represented an 85% recovery rate and their antigenicity, examined with anti-serotype specific antiserum, remained intact. This easy and reproducible procedure can be used to prepare purified ureaplasmas for investigation of ureaplasmal antigens and their expression and/or role in disease. PMID- 1865183 TI - Isolation and evolutionary analysis of a RepFVIB replicon of the plasmid pSU212. AB - We have isolated at least two different replication regions from pSU401, a Tn802 insertion derivative of the IncFVI plasmid pSU212. One of the replication regions (RepFVIB) is highly homologous to the RepFIIA replicon of IncFII plasmids, and thus belongs to the RepFIIA family. We have also cloned the incompatibility determinant (incFVI) and the copy number control gene (cop) from RepFVIB and determined their nucleotide sequences. The analysis of the sequences supports the idea of a modular evolution of RepFIIA plasmids. PMID- 1865184 TI - Production of type 5 capsular polysaccharide by Staphylococcus aureus grown in a semi-synthetic medium. AB - The concentration of the type 5 capsular polysaccharide (CP) antigen of Staphylococcus aureus can be measured directly in cultures or cell suspensions by a two-step inhibition enzyme-linked immunosorbent assay (ELISA), using monoclonal antibodies. CP was synthesized during growth on a variety of carbon substrates and its production was not affected by the nature of the carbon source. High levels of yeast extract inhibited CP formation. CP was synthesized in batch culture at the same rate during exponential growth as in the post-exponential phase. Post-exponential CP production contributed at least half the final amount of CP measured. This phenomenon was observed in different culture media, although the specific yield of polysaccharide varied from one medium to another. Post exponential CP production was observed in the pH range 6-7, but not at pH 8. Post exponential production was strictly dependent on oxygen availability and did not occur under anaerobic conditions. PMID- 1865185 TI - Determination of effector molecules in L-arabinose-induced bulge formation and lysis of Escherichia coli IFO 3545. AB - L-Ribulose 5-phosphate (L-Ru5P) was identified as the primary effector molecule of L-arabinose-induced bulge formation in Escherichia coli IFO 3545 observed in nutrient broth with 5% (w/v) sodium chloride. Hyperinduction of L-arabinose isomerase was due to exogenous sodium chloride and the resulting alteration in the balance of the L-arabinose-metabolizing enzymes resulted in accumulation of L Ru5P. L-Ru5P induced the lysis of an L-arabinose-negative, L-Ru5P 4-epimerase less mutant, ara-207, even when directly added to the medium but was not active against the wild-type strain. Some L-arabinose-utilizing (L-arabinose-resistant) revertants of ara-207 were still sensitive to L-Ru5P, indicating the involvement of another mutation in L-Ru5P-sensitivity other than genetic lack of L-Ru5P 4 epimerase. Among the various pentose phosphate esters tested, only L-Ru5P could induce lysis of ara-207. The lytic activity of L-Ru5P was attributed to its effect on bacterial sugar nucleotide metabolism which caused secondary accumulation of uridine 5'-diphosphate galactose (UDPGal), which provoked lysis induction. PMID- 1865186 TI - Phylogenetic analysis of five medically important Candida species as deduced on the basis of small ribosomal subunit RNA sequences. AB - The classification of species belonging to the genus Candida Berkhout is problematic. Therefore, we have determined the small ribosomal subunit RNA (srRNA) sequences of the type strains of three human pathogenic Candida species; Candida krusei, C. lusitaniae and C. tropicalis. The srRNA sequences were aligned with published eukaryotic srRNA sequences and evolutionary trees were inferred using a matrix optimization method. An evolutionary tree comprising all available eukaryotic srRNA sequences, including two other pathogenic Candida species, C. albicans and C. glabrata, showed that the yeasts diverge rather late in the course of eukaryote evolution, namely at the same depth as green plants, ciliates and some smaller taxa. The cluster of the higher fungi consists of 10 ascomycetes and ascomycete-like species with the first branches leading to Neurospora crassa, Pneumocystis carinii, Candida lusitaniae and C. krusei, in that order. Next there is a dichotomous divergence leading to a group consisting of Torulaspora delbrueckii, Saccharomyces cerevisiae, C. glabrata and Kluyveromyces lactis and a smaller group comprising C. tropicalis and C. albicans. The divergence pattern obtained on the basis of srRNA sequence data is also compared to various other chemotaxonomic data. PMID- 1865187 TI - Memory development in early childhood: encoding process in a spatial task. AB - A new kind of spatial task was devised to provide a description of the development of mnemonic strategy in early childhood. Five kinds of vertical arrays of drawings differing only in left-right orientation were presented one by one. Children at ages 5, 6, 7, and 9 years were asked to reconstruct the model. Most of the preschoolers succeeded only with those arrays in which drawings in the same orientation were juxtaposed. Memory for the most complicated array was not accurate enough until age 9. During the study, the oldest children usually verbalized the orientations as a sequence or the positions of the drawings in each orientation distinctively. This was interpreted as indicating that only the oldest children executed the sophisticated encoding strategies that integrate information on the orientation and position. Analysis of children's answers to the question about how to memorize revealed that awareness of using a strategy emerged at age 7 and grew clear by age 9. PMID- 1865188 TI - Preschoolers' construction order of event sequences related to mental ability and degree of familiarity. AB - Preschoolers' understanding of sequential relations was investigated in two experiments. Experiment 1 showed that appreciation of sequential relations depends on the level of mental ability and the degree of familiarity displayed with the social or behavioral phenomena under investigation. Experiment 2 reproduced the findings of Experiment 1 and, further, demonstrated that an increase in experience and familiarity through an interaction phase between children with higher and those with lower mental abilities led to a significant exchange of information and performance that was retained over the posttest phase. The data of both experiments are discussed within the framework of the "invariance hypothesis" (Bullock, 1985) in contrast to Piagetian theory (Piaget, 1946/1969). PMID- 1865189 TI - Stress as a predictor of the quality of parent-infant interactions. AB - Three predictor variables--vulnerability to stress, expectations for parenting stress, and low power attributions--were assessed for 21 couples during pregnancy. In-home observations of parent-infant interactions occurred 4 months postnatally. Stepwise multiple regression analyses, calculated separately for mothers and fathers, revealed that prenatal stress factors were more successful in predicting father-infant interactions. On the interaction variable basic care, 67% of the variance was explained by fathers' parenting stress expectations, stress vulnerability, and attributions for low power, whereas only 2% of the variance on basic care was explained by maternal scores on the same variables. Results of this study indicated that parent-infant interactions are affected by parental attitudes and personality characteristics. The present research also underscored the continued need to study the differential effects of gender on parent-infant interactions. PMID- 1865190 TI - Developmental status and AIDS attitudes in adolescence. AB - We postulated that among adolescents and young adults, the development of consistent and responsible attitudes with respect to acquired immunodeficiency syndrome (AIDS) precautions would follow a pattern similar to that of the development of a sense of identity. Late-adolescent trainee teachers and nurses (N = 262) were administered identity and intimacy measures and a questionnaire measuring attitudes toward and knowledge of AIDS prevention. Attitudes were shown to be conceptually complex, with dimensions expressing the identity statuses of diffusion, foreclosure, moratorium, and achievement. Few relationships were found between AIDS attitudes and sex, course, measures of identity, or intimacy. However, attitudes toward AIDS precautions and identity status were predictive of future intention to use a condom. Intimacy level was negatively related to such an intention, suggesting that those in steady relationships may not recognize the need for AIDS protection. PMID- 1865191 TI - Self-reported depression in younger and older pregnant inner-city adolescents. AB - Younger (14- to 17-year-old) inner-city adolescent mothers have been reported by Colletta (1983) as being more depressed than older (18- to 19-year-old) inner city adolescent mothers. To determine whether this finding applies to pregnant adolescents, the revised Beck Depression Inventory (BDI; Beck, Rush, Shaw, & Emery, 1979; Beck & Steer, 1987) was administered to 175 (65.1%) Black, 64 (23.8%) Hispanic, and 30 (11.1%) White inner-city adolescents during their 28th week of pregnancy. The sample was divided into 129 (48.0%) younger (13- to 15 year-old) adolescents and 140 (52.0%) older (16- to 18-year-old) adolescents. The mean profiles of the 21 BDI symptoms were comparable for both age groups, and it was concluded that younger and older pregnant inner-city adolescents describe similar levels of self-reported depression. PMID- 1865192 TI - Venturesomeness, impulsiveness, and Eysenck's personality dimensions: a study among Australian adolescents. AB - In Eysenckian personality theory, the dimension extraversion has traditionally consisted of two elements, sociability and impulsiveness. More recently, however, impulsiveness has become associated with the dimension psychoticism (Rocklin & Revelle, 1981), although subfactors of impulsiveness have been shown to be differentially related to extraversion and psychoticism (S. Eysenck & H. Eysenck, 1977). This study investigates the structures of impulsiveness and venturesomeness and their association with extraversion, emotional stability neuroticism, and psychoticism among 170 Australian adolescents. Both impulsiveness and venturesomeness were found to be multidimensional, although the subfactors differed slightly from those suggested by the Eysencks. No support was found for the view that impulsiveness narrowly defined is pathological, although the impulsiveness and venturesomeness subfactors were found to be differentially related to extraversion, emotional stability-neuroticism, and psychoticism. The theoretical implications of these findings are briefly discussed. PMID- 1865193 TI - Psychophysiological aspects of nightmares, night terrors, and sleepwalking. AB - Monitoring sleep through electroencephalography and electroculography has identified the different sleep stages in which nightmares, night terrors, and sleepwalking occur. Questionnaire surveys have supplemented the findings of case studies of these sleep disorders. Neurotransmitters operative during these sleep disorders have enlarged the knowledge of the psychophysiological dimensions especially of nightmares. PMID- 1865194 TI - Induced rotary movement during eye movements: displays with unequal spacing of pattern. AB - In my previous (Reinhardt-Rutland, 1982) study, I suggested that eye movements enhance induced rotary movement. However, low salience of absolute displacement might also explain the results, as displays were covered with large numbers of equally spaced radial pattern elements. To test these competing hypotheses in the present study, I used an unequally spaced pattern in two displays. Common to each display was an annulus: In one display, the common annulus surrounded a disk, and in the other display the common annulus was surrounded by another annulus. In any trial, one component rotated and the other was stationary while for 40 s the subject's eyes followed a circular path concentric with the display; subjects timed those occasions when perceived stronger rotation resided in the common annulus. Despite an unequally spaced pattern, absolute displacement had a barely significant effect. Instead, perceived stronger rotation mostly resided in a display's more central component. I concluded therefore that eye movements enhance induced rotary movement. PMID- 1865195 TI - Testing organization preferences in serial pattern learning. AB - Subjects studied a series of colored dots for 6 s and then performed a memory reproduction task for which they chose alternative puzzle pieces from a set. Series were presented repeatedly until subjects made a completely correct reproduction. The puzzle pieces contained parts of the series that were expected to interact with the groups identified by spontaneous perceptual organization. By assuming that same grouping in series and puzzle pieces would be preferred, the preferences could be predicted on the basis of an economy principle. The preferences obtained were in accordance with the predictions. PMID- 1865196 TI - Partial report: iconic store or two buffers? AB - Selective recall of a subset of letters from a multiletter array declines systematically with increases in the delay of the partial report cue. The issues addressed were (a) whether such a decline is due to progressive loss of location information or to systematic loss of features and (b) whether partial report is the result of a select-then-identify or an identify-then-select process. Instructing the subjects to guess or not to guess had an effect of intra-array, displacement, and extra-array errors. Emphasizing on recall location affected both intra- and extra-array errors. The interstimulus interval manipulation had an effect on extra-array errors as well as on intra-array errors. These observations are contrary to the suggestions that intra-array errors are due to loss of location information and that extra-array errors are indicative of a joint effect on misidentification due to chance and the ratio of extra-array errors to intra-array errors. Some other results are difficult for a dual-buffer model but can readily be accounted for by the orthodox view of the iconic store. PMID- 1865198 TI - St Vitus (286-302). PMID- 1865197 TI - Epilepsy after first seizures: risks and implications. PMID- 1865199 TI - Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra, and differential cell death in Parkinson's disease. AB - In six control subjects pars compacta nerve cells in the ventrolateral substantia nigra had a lower melanin content than nerve cells in the dorsomedial region. This coincides with a natural anatomical division into ventral and dorsal tiers, which represent functionally distinct populations. In six cases of Parkinson's disease (PD) the ventral tier showed very few surviving nerve cells compared with preservation of cells in the dorsal tier. In 13 subjects without PD, but with nigral Lewy bodies and cell loss, the degenerative process started in the ventral tier, and spread to the dorsal tier. This pattern of selective degeneration of nigrostriatal neurons is not seen in ageing or after acute administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). PMID- 1865200 TI - Pure akinesia: an atypical manifestation of progressive supranuclear palsy. AB - Two patients with "pure akinesia" who showed the characteristic changes of progressive supranuclear palsy (PSP) at necropsy are described. They had akinesia but no rigidity or tremor, and ophthalmoplegia was not observed during the course of illness. The symptoms of "pure akinesia" was not improved by levodopa therapy but was considerably improved by L-threo-3,4-dihydroxy-phenylserine. At necropsy, pathological findings were not different from those reported for PSP. It is suggested that "pure akinesia" is an atypical manifestation of PSP, and that norepinephrinergic neurons may be involved in some types of PSP. PMID- 1865201 TI - Comparison of the clinical pharmacology of (-)NPA and levodopa in Parkinson's disease. AB - Direct acting dopamine agonists are generally less effective than levodopa in relieving symptoms of Parkinson's disease. In an attempt to quantitate and explain this situation, the acute motor responses to intravenous injections of the dopamine agonist, (-)-N-n-propyl-norapomorphine hydrochloride (NPA), were compared with those of the dopamine precursor, levodopa. At optimum dose levels, the acute anti-Parkinsonian efficacy of NPA averaged only about 50% of maximum, while essentially total symptom suppression was obtained with levodopa in patients previously treated with the amine precursor. Dyskinesia severity, however, was similar with the two drugs. These differences in anti-Parkinsonian efficacy may reflect the fact that while NPA acts mainly on D-2 dopamine receptors, levodopa results in stimulation of both the D-1 and D-2 subsets of receptors at a more physiological ratio. Future efforts to develop dopamine agonists for the treatment of Parkinsonian symptoms may thus have to consider focusing on drugs having pharmacological profile more similar to that of dopamine. PMID- 1865202 TI - Actuarial analysis of the occurrence of remissions following thymectomy for myasthenia gravis in 400 patients. AB - The role of thymectomy in the treatment of myasthenia gravis (MG) was analysed in 400 patients affected with generalised MG operated on between 1974-83, and prospectively followed up for five years after surgery. The occurrence of stable remission (SR) (that is, complete clinical drug-free remission that remains stable for all the subsequent follow up) was the endpoint of survival analyses and the distribution of SR time (SRT, that is, the interval from thymectomy to the occurrence of SR) was assessed by actuarial and Cox multivariate analyses. SRT distribution after surgery showed a slow progressive increase of cumulative SR rate that could both be ascribed to a delayed effect of thymectomy as well as reflect the natural history of MG, itself characterised by an increasing probability of spontaneous remission with time. SRT distribution was similar after stratification for all variables studied except when patients without thymoma were stratified for the need for immunosuppressive treatment in addition to thymectomy. Patients without thymoma who did not require additional immunosuppressive therapy (n = 130) had the highest SR rate occurring in the two years after thymectomy, and differed from patients treated with immunosuppressive drugs who showed the highest SR rate five years after surgery. Actuarial analysis has therefore identified a subgroup of patients where SR, occurring in the first years after surgery, is more likely to be ascribed to thymectomy than merely reflect the natural course of the disease. PMID- 1865203 TI - Macrocytosis in multiple sclerosis. A study in 82 de novo Arab patients. AB - Macrocytosis, without anaemia, was common in 82 de novo multiple sclerosis patients compared with a similar number of age and sex matched controls. This was an early phenomenon in the course of the disease and was not influenced by the age of the patients nor the duration of the disease. None of the patients proved to have pernicious anaemia, yet the similarity in the geographical and sex distribution as well as the similarity in HLA associations of multiple sclerosis and pernicious anaemia may indicate that both diseases are under similar genetic influence. PMID- 1865204 TI - Benign vascular sexual headache and exertional headache: interrelationships and long term prognosis. AB - There is a definite relationship between the vascular type of benign sexual headache and benign exertional headache. Forty five patients with benign vascular sexual headache were reviewed. Twenty seven (60%) experienced benign vascular sexual headache alone and eighteen (40%) had experienced both benign vascular sexual headache and benign exertional headache on at least one occasion. The mean age was 34.3 years with a male:female ratio of 5.4:1. Thirty patients with a history of benign vascular sexual headache were followed for an average of 74 months. A personal history of migraine was found in 47% of cases and a family history of migraine in 30%. Forty one per cent of patients with benign vascular sexual headache alone had recurrences after diagnosis, and stress and fatigue were considered major contributing factors to the initial and recurrent headache. Nine patients had experienced benign vascular sexual headache and benign exertional headache within 72 hours of each other on at least one occasion, often with a residual headache between the two. Four patients experienced their benign vascular sexual headache and benign exertional headache separated by months to years. The prognosis of benign vascular sexual headache and the clinical and possible pathophysiological relationships between benign vascular sexual headache and benign exertional headache are discussed. Knowledge of the interrelationships of these varieties of headache is valuable in the counselling of patients. PMID- 1865205 TI - Maternal reporting of behaviour following very severe blunt head injury. AB - Mothers of 40 very severely head injured male subjects rated their son's behaviour on the Current Behaviour Scale and their ratings were compared with mothers' ratings of 40 control male subjects. The scale was able to discriminate the two groups, by utilising two factors--loss of emotional control and loss of motivation. The mothers' level of emotional distress was closely related to their reporting of loss of emotional control in their sons, but reporting of loss of motivation, or lowered arousal, was strongly predicted by the functional disability of the son. The utility of refining the measurement of post-trauma behaviour is discussed. PMID- 1865206 TI - Glial swelling following human cerebral contusion: an ultrastructural study. AB - The ultrastructural features of cerebral contusion seen three hours to 11 days after head injury were studied in 18 patients undergoing surgery. Massive astrocytic swelling ("cytotoxic" oedema) was seen three hours to three days after injury, maximal in perivascular foot processes, and compressing some of the underlying capillaries. The tight junctions were not disrupted. Neuronal damage was most marked three to 11 days after injury. The pathophysiological mechanisms leading to oedema formation and neuronal degeneration are discussed. PMID- 1865207 TI - Vigabatrin and psychosis. AB - We report a series of 14 cases of psychosis occurring in patients with severe intractable epilepsy, following the prescription of vigabatrin, a new antiepileptic drug. Nine patients had no previous history of psychosis. In eight patients the psychosis occurred following a change in the habitual pattern of seizure activity; in four it developed after a period of seizure freedom followed by a cluster of seizures, and in the other four patients an alternating psychosis was observed. In five patients there was no clear relationship to seizure pattern. Another patient developed psychosis after taking an overdose of between eight and 12 g of vigabatrin. A further three patients, who developed psychosis following vigabatrin withdrawal, were not included in this series. The mean dose at onset of the psychosis (excluding the patient who took an overdose) was 2580 mg, and the period from initiation of therapy to the onset of psychosis varied from five days to 32 weeks (and occurred 24 hours after the overdose of vigabatrin). In all cases the psychosis resolved, but necessitated the withdrawal of vigabatrin, except in the single patient who took the overdose. The mechanism of this behaviour change is unclear, but in some instances may reflect vigabatrin's powerful anti-epileptic action. This is clearly not the case for all patients. Vigabatrin should be started with caution in patients with severe epilepsy, particularly in the presence of a previous history of psychosis, and such patients should be carefully monitored. PMID- 1865208 TI - Changes in intracranial CSF volume after lumbar puncture and their relationship to post-LP headache. AB - Post-lumbar puncture (LP) headache may be due to "low CSF pressure", leading to stretching of pain sensitive intracranial structures. The low intracranial pressure is secondary to net loss of intracranial CSF. It has, however, not been possible to measure intracranial CSF volume accurately during life until recently. Intracranial CSF volume can now be measured non-invasively by a MRI technique. The changes in intracranial CSF volume were studied in 20 patients who had LP. Total intracranial CSF volume was reduced in 19 of the 20 patients 24 hours after LP (range -1.8 mls to -158.6 mls). Most of the CSF was lost from the cortical sulci. Very large reductions in intracranial CSF volume were frequently related to post-LP headache but some patients developed headache with relatively little alteration in the intracranial CSF volume. There was not a measurable change in position of the intracranial structures following LP. PMID- 1865209 TI - Posterior cortical dementia with alexia: neurobehavioural, MRI, and PET findings. AB - A progressive disorder of relatively focal but asymmetric biposterior dysfunction is described in a 54 year old right handed male. Initial clinical features included letter-by-letter alexia, visual anomia, acalculia, mild agraphia, constructional apraxia, and visuospatial compromise. Serial testing demonstrated relentless deterioration with additional development of transcortical sensory aphasia, Gerstmann's tetrad, and severe visuoperceptual impairment. Amnesia was not an early clinical feature. Judgment, personality, insight, and awareness remained preserved throughout most of the clinical course. Extinction in the right visual field to bilateral stimulation was the sole neurological abnormality. Early CT was normal and late MRI showed asymmetrical bioccipitoparietal atrophy with greater involvement of the left hemisphere. Results from positron emission tomography (PET) showed bilaterally asymmetric (left greater than right) occipitotemporoparietal hypometabolism. The metabolic decrement was strikingly asymmetric with a 50% reduction in glucose consumption confined to the left occipital cortex. The picture of occipitotemporoparietal compromise verified by MRI, PET, and neurobehavioural testing would be unusual for such degenerative dementias as Alzheimer's (AD) and Pick's disease, although atypical AD with predominant occipital lobe involvement cannot be excluded. This case supports the concepts of posterior cortical dementia (PCD) as a clinically distinct entity and for the first time documents its corresponding metabolic deficit using PET. PMID- 1865210 TI - A case of progressive encephalomyelitis with rigidity and positive antiglutamic acid decarboxylase antibodies [corrected]. AB - A 50 year old woman developed progressive encephalomyelitis with rigidity over a three year period. Her CSF contained oligoclonal bands and both her serum and CSF contained antibodies directed against GABA-ergic synapses (antiglutamic acid decarboxylase [corrected] antibodies). These antibodies have recently been described in cases of stiff man syndrome. Both disorders may be part of a clinical spectrum that has an underlying autoimmune basis. PMID- 1865211 TI - Deficiencies in anti-acetylcholine receptor antibody measurement in myasthenia gravis. AB - In a retrospective case note study of 86 patients with myasthenia gravis, 60 had an anti-acetylcholine receptor antibody assay performed by the regional immunology laboratory. Antibody was detected in 38% which compares with 66-93% in other series. Whilst the use of staphylococcal protein A to precipitate the antibody-receptor complex, rather than anti-human immunoglobulin, may be partly responsible for this low sensitivity, other methodological problems are likely to exist. It is suggested that this potentially critical assay becomes a subject for regular audit. PMID- 1865213 TI - Neurocysticercosis: regression of a fourth ventricular cyst with praziquantel. AB - Symptomatic intraventricular cysticerci are said to respond poorly to the anticestodial agent praziquantel. A case is reported of rapid regression of a large cyst of the fourth ventricle after oral praziquantel, avoiding the need for surgery. PMID- 1865212 TI - Contractile properties of lower leg muscles are normal in Parkinson's disease. AB - Contraction parameters (time-to-peak and half relaxation time), responses to short tetani and resistance to stretch were studied in the lower leg muscles of Parkinsonian patients and in age-matched controls. It was possible to distinguish between muscle groups of different fibre type composition in normal subjects on the basis of their contraction and relaxation velocities. These parameters, however, failed to show any abnormalities in the patient group. The only abnormal finding in Parkinsonian subjects was an increased resistance to passive stretch under static conditions, presumably elastic in origin. The results are evidence against a contribution of altered contractile properties to muscular rigidity in Parkinsonism. PMID- 1865214 TI - Neurosurgical complications after intranasal ethmoidectomy. AB - Intranasal ethmoidectomy is a common otolaryngological procedure. Despite the potential for serious intracranial complications, there is a paucity of reports describing the neurosurgical complications of the procedure. Two patients with intracranial complications of intranasal ethmoidectomy, and the relevant medical literature, are reviewed. The anatomy of the ethmoid air cells and their relation to the intracranial cavity are described. The importance of definitive, emergent repair with attention to the potential for vascular injury is discussed. PMID- 1865215 TI - Early heparin therapy in patients with spontaneous intracerebral haemorrhage. AB - In 68 patients with spontaneous intracerebral haemorrhage the effect of heparin treatment beginning on the second, fourth or tenth day was investigated. Early (day 2) low-dose heparin medication significantly lowered the incidence of pulmonary embolism. An increase in the number of patients with rebleeding was not observed. The results indicate that the early use of heparin in these patients is safe and can be recommended for the prevention of thromboembolic complications. PMID- 1865216 TI - Treatment of persistent hiccups. PMID- 1865217 TI - Postradiation motor neuron syndrome of the upper cervical region--a manifestation of the combined effect of cranial irradiation and intrathecal chemotherapy? PMID- 1865218 TI - Optic nerve cysticercosis: a case report. PMID- 1865219 TI - Vertebral haemangioma causing acute recurrent spinal cord compression. PMID- 1865220 TI - Giant intracranial aneurysm associated with Marfan's syndrome: a case report. PMID- 1865221 TI - Binswanger's disease: neither Binswanger's nor a disease. PMID- 1865222 TI - Isolated and combined pareses of cranial nerves III, IV and VI. A retrospective study of 412 patients. AB - We evaluated the hospital records of 412 patients with isolated or combined ocular nerve palsies in a retrospective study. Palsies of the oculomotor nerve (n = 172) and of the abducens nerve (n = 165) were more frequent than those of the trochlear nerve (n = 25). Combined ocular nerve palsies (n = 50) were generally combinations of the 3rd and 6th cranial nerves (n = 21) or pareses of all three ocular nerves (n = 17). 165 ocular nerve palsies were due to vascular causes: in 135 of these cases diabetes mellitus and hypertension were present. The oculomotor nerve was most frequently affected; in 63% there was no involvement of the pupil. In inflammatory disease and brain tumor the abducens nerve was most frequently affected, with aneurysm of the oculomotor nerve. The origin of ophthalmoplegia was unclear in 73 patients. Ocular nerve paralysis was most common with tumors, aneurysm, and vascular processes and in 206 cases was only partial. Pain was associated with tumor, trauma and aneurysm. In trochlear nerve palsies concomitant pain was much less frequent than in palsies of the other two ocular nerves. The clinical course was followed for 3 weeks in 352 patients; in 191 patients there was a complete regression of the pareses and in 59 only a partial recovery. The most favorable prognosis was with inflammatory and vascular lesions; in the latter the outcome was improved by the administration of non steroidal anti-inflammatory drugs. PMID- 1865223 TI - Intrathecal humoral immune reaction in zoster infections. AB - Intrathecal humoral immune reaction in 26 patients with a reactivation of varicella-zoster virus was analyzed. 11 suffered from ganglionitis, in 7 cases an additional affection of the lower motor neuron was demonstrable. In 8 patients, meningitis, myelitis or cerebral infarctions by zoster angiitis were diagnosed. Intrathecal immune reaction in ganglionitis was weak whereas an intense IgG synthesis became demonstrable in all meningomyelitis/cerebral infarction cases. As demonstrated by immunoblotting, in early stages of the disease immune reaction in serum and cerebrospinal fluid differed only quantitatively. In the further course, most intrathecally synthesized antibodies were directed against low molecular antigens whereas serum pattern did not change. In some patients, additional antibodies not detectable in serum were demonstrable. Though intensity markedly differed, no qualitative differences between the immune response in ganglionitis and more widespread zoster infections of the CNS were detectable. PMID- 1865224 TI - A private practice model for teaching and research activities. AB - The majority of neurologists in the United States are in fee for service patient management, dividing their time between hospital and office based practice. Many have had subspecialty training or have had research experience. It is our belief that research should be a component of a neurologist's practice. This is particularly true for an assessment of outcome. In order to accomplish this, we have developed a system which includes patient management, teaching, and clinical research, within our fee for service model. PMID- 1865225 TI - Resistance to hypoxic conduction block in sciatic nerves of rats with streptozotocin-induced diabetes mellitus. AB - This study describes the electrophysiological responses of endoneurial preparations derived from rat sciatic nerve to acute hypoxia in vitro. Preparations from control rats exhibited a marked decline in compound action potential (CAP) amplitude coupled with an increase in latency, during 40 minutes exposure to 8% O2. In contrast, preparations from 4 week streptozotocin-diabetic rats showed a greatly reduced decline in CAP amplitude, with an increase in latency. Twice-daily insulin treatment of diabetic rats resulted in a pattern of CAP amplitude decline that initially resembled that of untreated diabetics but by 40 min was similar to controls, with latency again increasing during hypoxia. Nerves were also maintained in 25 mmol/l glucose, rather than the 5 mmol/l glucose of the above studies. Under such conditions the performance of nerves from diabetic rats was unaltered. Nerves from control rats exhibited an initial resistance to hypoxia but by 40 min CAP had declined to values of control rats maintained in 5 mmol/l glucose. An increase in latency during hypoxia was also noted in preparations from control or diabetic rats maintained in 25 mmol/l glucose. The maintenance of CAP amplitude during hypoxia by diabetic preparations is initially related to increased substrate availability, with an additional component that is not related to external glucose levels in vitro, and is absent after insulin treatment of diabetic rats. PMID- 1865226 TI - Cerebral angiotropic large cell lymphoma (neoplastic angioendotheliosis): therapeutic considerations. AB - Cerebral angiotropic large cell lymphoma (neoplastic angioendotheliosis) is a rare disease with a particular propensity to affect the central nervous system by vascular occlusion. Because the disease is rare and there are no specific diagnostic procedures apart from cerebral biopsy, it is difficult to diagnose in life. Accordingly, chemotherapy or radiotherapy has only rarely been attempted and their effectiveness is uncertain. We established the diagnosis in a 62-year old patient by cerebral biopsy and observed remission following institution of combination chemotherapy. Unfortunately, neurologic deterioration recurred during maintenance chemotherapy. We identified 30 patients in the literature who initially presented with definite central nervous system manifestations and whose clinical conditions were described sufficiently enough for comparison with our case. Eleven patients had the diagnosis made in life, but only 5 received chemotherapy other than corticosteroid hormones. Our patient's survival for 16 months exceeded that in the majority of the 30 reported cases. Intense anti lymphoma chemotherapy, and possibly radiotherapy, may be beneficial and should be studied in this otherwise rapidly fatal disease. It seems certain that early diagnosis is essential if therapeutic intervention is to be successful. PMID- 1865227 TI - Centronuclear myopathy: clinical, morphological and genetic characters. A review of 288 cases. AB - We reviewed the 288 cases of centronuclear (myotubular) myopathy reported in the literature to correlate the clinical findings with the different modes of inheritance. Autosomal dominant (AD) inheritance occurred in 65 patients in 14 families. Recessive X-linked transmission (XLR) was present in 84 males belonging to 14 families. In 54 familial cases and in 85 isolated cases the mode of inheritance was uncertain. The clinical picture was very severe in the XLR form with most dying in the first year of life, and more heterogeneous and much less severe in the AD form. Clinico-genetic analysis of unclassified familial and isolated cases suggested that most of them fitted in either the AD and the XLR form. The diagnosis of the autosomal recessive mode of inheritance, in the past considered to be the most frequent type, is possible in a minority of cases and is difficult to document. PMID- 1865228 TI - Norepinephrine and epinephrine responses to postural stimulus in orthostatic hypotension due to brainstem ischemic lesions. AB - Norepinephrine (NE) and epinephrine (E) responses to upright posture were investigated in 25 patients with orthostatic hypotension due to brainstem ischemic lesions and in 25 control subjects. In controls the postural stimulus induced constantly a rise in NE urinary excretion and a reduction in E excretion, while in patients with orthostatic hypotension it caused a depression in NE urinary excretion and a rise in E urinary excretion; the last alteration was noticed in all but one patient. The E discharge induced by posture in patients with orthostatic hypotension may be involved in the reduction of vascular peripheral resistance and then in postural fall of blood pressure displayed by such patients. PMID- 1865229 TI - Multiple sclerosis in Cyprus. AB - The prevalence of multiple sclerosis (MS) was studied in the Greek-speaking population in the southwestern district of Paphos and the eastern Famagusta area and in the Troodos mountains in Cyprus. Excluding refugees from the northern part of the island, the MS prevalence was 44.5 per 100,000. This is a similar prevalence to that found in Sicily and shows that, like Sicily, Greek-speaking Cypriots have a medium to high and not a low MS prevalence. There was no significant difference in MS prevalence between the warm Paphos and Famagusta areas and the much colder mountainous areas. In one village, Liopetri, there were five families with definite MS (CDMS), and one patient with clinically probable MS (CPMS). Excluding refugees, the prevalence for CDMS and CPMS in this village was 240 per 100,000. All six families are probably related. PMID- 1865230 TI - MELAS of infantile onset: mitochondrial angiopathy or cytopathy? AB - An 83-day-old male infant had convulsions, hypertrophic cardiomyopathy, and lactic acidosis. Cranial computed tomography revealed low-density areas in both parieto-occipital lobes and in the left temporal lobe. Muscle biopsy did not reveal ragged-red fibers, but abnormal mitochondria were found in the capillary endothelial cells as well as in the muscle fibers. At 5 months of age, the patient developed purpura on the soles and palms. Skin biopsy showed degeneration of the endothelial cells with abnormal mitochondria in the arterioles and capillaries. Myelinated nerves in the skin had vacuolated axons with swollen mitochondria, and their myelin sheaths showed vacuolation. At 9 months of age, he died of heart failure, and autopsy revealed abnormal mitochondria in the myocardium but not in the coronary vessels. Our findings indicate that the symptoms of the mitochondrial encephalopathy, myopathy, lactic acidosis, and strokelike episodes (MELAS) syndrome cannot be fully explained by the mitochondrial angiopathy alone. PMID- 1865231 TI - Syphilitic meningitis causing paraparesis in an HIV-negative woman. AB - Syphilitic meningitis, which can occur near the time of secondary syphilis, is frequently asymptomatic. There has been one recent report of an HIV-positive patient who developed syphilitic polyradiculopathy following a recent history of secondary syphilis. We describe an HIV-negative woman in whom paraparesis occurred secondary to syphilitic meningitis. Complete recovery followed a course of high-dose intravenous penicillin therapy, emphasizing the treatable nature of this cause of paraparesis. PMID- 1865232 TI - Dopa-sensitive and dopa-resistant gait parameters in Parkinson's disease. AB - Quantitative analysis of gait was performed in 20 parkinsonians before and 1 h after the acute administration of L-Dopa in order to discriminate between the Dopa-sensitive and the Dopa-resistant kinematic gait parameters. The stride length and the kinematic parameters (swing velocity, peak velocity) related to the energy were Dopa-sensitive. The improvement of the bent forward posture by L Dopa may explain the stride length increase. Temporal parameters (stride and swing duration, stride duration variability), related to rhythm, were Dopa resistant. Experimental data argue for the importance of force control in maintaining the posture. The stride length variability, possibly related to the variability of force production shown to exist in parkinsonians was not significantly improved by L-Dopa. In Parkinson's disease different hypotheses might explain the inexorable aggravation of gait disorders along the course of the disease: (1) an advancing disorder of coordination between postural control and locomotion, (2) if some gait parameters like stride length and kinematic parameters are Dopa-sensitive, the others are Dopa-resistant and thus may involve other mechanisms than dopamine deficiency. PMID- 1865233 TI - Multisystem involvement of the central nervous system in Strumpell's disease. A neurophysiological and neuropsychological study. AB - The multisystem involvement of the central nervous system (CNS) in familial spastic paraplegia (FSP) has not been fully investigated by means of complete neurophysiological and neuropsychological examinations. The classification which distinguishes pure and complicated forms of FSP, is based on clinical features and does not take into account the possibility that clinically silent lesions of the CNS can be identified by means of adequate tests. The study was intended to assess the subclinical and multisystem involvement of the CNS in a group of 11 patients affected by FSP, clinically distinguished in 7 pure forms and 4 complicated forms. Neurophysiological tests included saccadic eye movements analysis, visual and auditory brain stem evoked responses. Neuropsychological examination was devised by means of a special purpose mental deterioration battery. Our results, showing a high incidence of multisystemic subclinical involvement of the CNS, confirm and extend the concept that FSP is a multisystemic degenerative disease of the CNS, and that the existence of "pure" forms should be reconsidered. PMID- 1865234 TI - Historical aspects of neurosciences. Otto Binswanger (1852-1929). PMID- 1865235 TI - Limb-girdle syndrome: a genetic study of 22 large Brazilian families. Comparison with X-linked Duchenne and Becker dystrophies. AB - The differential clinical diagnosis between the X-linked muscular dystrophies (DMD and BMD) and autosomal recessive limb-girdle muscular dystrophy (LGMD), which is extremely important for genetic counseling, may be very difficult. The aim of the present report is to describe clinical and laboratory findings in patients from large families, with AR inheritance, in an attempt to characterize better cases which have been diagnosed as LGMD compared with the X-linked forms. The main features analysed are: age of onset and of confinement to a wheelchair, reproductive performance, serum enzymes (CK and PK) and dystrophin assessment (through immunohistochemistry and Western blot). Twenty-two families, with 62 affected patients diagnosed as limb-girdle muscular dystrophy, were included in this report. In 19 families, the patients had a milder clinical course, while in the remaining 3, the progression of the disease was continuous and clinically similar to X-linked DMD ("DMD-like"). A high consanguinity rate was observed among the parents of the affected patients (77%). No major clinical difference was observed between the X-linked and the AR forms. However, muscle dystrophin was found qualitatively and quantitatively normal in the autosomal forms but absent or abnormal in the X-linked ones. The reproductive performance was significantly higher for male than female patients. In addition, a surprising finding was the significantly greater fitness estimated for male LGMD cases as compared with Becker patients of comparable age studied in our center. The implications of such findings are discussed. PMID- 1865236 TI - Amplifications of multiple regions of the HTLV-I genome from DNA of an Italian spastic paraparesis patient but not from DNA of multiple sclerosis patients. AB - We searched for evidence of infection by the human T-cell lymphoma/leukemia virus type I (HTLV-I) in patients with multiple sclerosis (40 cases); brainstem encephalitis (1 case); Friedreich's ataxia (1 case); spastic paraparesis of unknown etiology (1 case). All patients were from the region of Abruzzo, Italy. Sera were all negative for anti-HTLV-I reactivity by the Western blotting (WB) analysis. DNAs from peripheral blood mononuclear cells were amplified using the polymerase chain reaction (PCR) technique with primers specific for the HTLV-I gag, pol, and env proviral regions. HTLV-I sequences were amplified only in the patient with spastic paraparesis of unknown etiology. In this case, HTLV-I infection might have been related to blood transfusions received 2 years prior to the onset of the neurologic symptoms. Members of the patient's family were negative for HTLV-I by PCR and WB. These data indicate that HTLV-I associated myelopathy is present also in Italy, but fail to substantiate an association of HTLV-I with multiple sclerosis. PMID- 1865237 TI - Polarity of the surface and cortex of the amphibian egg from fertilization to first cleavage. AB - The anuran egg is polarized along its animal-vegetal axis and becomes bilaterally symmetrical before first cleavage. Functional sperm entry is regionally restricted to the animal hemisphere of the egg, and functional sperm entry does not occur after egg activation. This regional and functional restriction in sperm entry correlates with the presence of long, slender microvilli and with the presence of the filamentous component of the glycocalyx. After sperm fusion, the egg undergoes activation, including a depolarization of the membrane potential and exocytosis of granules in the cortex. Both of these activation responses are the result of a propagated increase in intracellular calcium. The egg's ability to undergo a propagated activation response develops after germinal vesicle breakdown and depends on the development of the cortical endoplasmic reticulum. Once activated, the radial symmetric egg acquires bilateral symmetry due to a rotation of the egg cortex relative to the inner cytoplasm. A transient array of parallel microtubules forms near the vegetal cortex and may be part of the motor driving the cortical rotation. PMID- 1865238 TI - Three-dimensional imaging of fertilization and early development. AB - The field of biological microscopy has recently enjoyed major technical advances, exemplified by the development of field-emission low-voltage scanning electron microscopes and laser scanning confocal light microscopes. In addition, computer processing of microscopical data is revolutionizing the way morphological information is imaged. In this paper, we illustrate methods by which this new technology can be used to examine events in fertilization and early development in three dimensions. Different types of specimen preparation protocols, using both echinoderm and mammalian gametes and embryos, are evaluated for their ability to preserve accurately the three-dimensional organization of these specimens for imaging by both low-voltage scanning electron microscopy and laser scanning confocal light microscopy. PMID- 1865239 TI - Fertilization of the mouse oocyte. AB - This paper presents morphological data on mouse oocyte maturation and fertilization, reviews evidence supporting the existence of a sperm receptor, and suggests future directions for this line of research. We used scanning electron microscopy to examine oocytes under a variety of conditions. The surfaces of mature mouse oocytes are seen to be similar whether maturation occurs in vivo or in vitro. Capacitated sperm (both acrosome-intact and acrosome-reacted) are observed to interact with the microvilli of the oocyte surface. Little is known about oocyte surface proteins that mediate fertilization in mammals. Data of ours and others show that enzyme treatment of live unfertilized eggs interferes with sperm binding. Enzyme treatment (trypsin, chymotrypsin treatment, or pronase) reduces the number of bound sperm, suggesting removal of a surface protein involved in fertilization. Trypsin treatment also causes some lengthening of surface microvilli in a belt surrounding the metaphase II region. After metabolic labeling, proteins of zona-free unfertilized eggs can be identified by SDS-PAGE and autoradiography. Comparison of 1-D gels from untreated and enzyme-treated eggs show the nearly complete disappearance of proteins of 263, 170, 137, 97, and 87 kD after digestion; an increase in a 66 kD protein after trypsin or chymotrypsin; and a major new band of 20 kD after chymotrypsin treatment. Fertilized eggs show the loss of a 255-265 kD band among other changes. Proteins of 97 kD and 87 kD were seen previously by surface labeling (Johnson and Calarco, 1980b), and our 97 kD and 66 kD bands are similar in molecular weight to those identified by Boldt et al. (1989). Taken together, these data identify a few candidate proteins for the role of sperm receptor on the egg surface. Future work should focus on identification of the surface protein(s) which functions physiologically in fertilization by developing fertilization-blocking antibodies. Relatedness to other mammalian sperm receptors and identification of the genes involved would provide valuable information to our understanding of fertilization and to the problems of infertility and contraception. PMID- 1865240 TI - Physiology and pathophysiology of the human spermatozoon: the role of electron microscopy. AB - In this article, the major contributions of electron microscopy to the present understanding of the physiology and pathophysiology of the human spermatozoon are reviewed. The ultrastructural organization of sperm organelles playing a significant role for cell function and, therefore, for the reproductive process is described. Also, the major abnormalities and defects of the various organellar systems and how they impair the reproductive function and/or the viability of the cell are reviewed. PMID- 1865242 TI - Versatile controlling system for cryopreparation techniques in electron microscopy. AB - A new setup for freeze-substitution and a versatile controlling system has been developed. Our goal was to build a simple system allowing precise control of the physical parameters of freeze-substitution experiments to learn more about their influences on the cellular ultrastructure and immunoreactivity of macromolecules. An improved apparatus for freeze-substitution, based on liquid nitrogen cooling, and a universal software for controlling the complex preparation protocols from cryofixation to final polymerization are described. This controlling system has the following advantages: it allows precise control and registration of temperature profiles, reconstruction of each individual step of previous experiments, and optimization of working conditions. The setup of the freeze substitution apparatus is designed to run many different substitution media in parallel; freeze-substitution (cryostat), embedding (working platform), and polymerization are carried out at separate places; therefore, more experiments can be done simultaneously. The ergonomic working platform allows exchange of media at controlled temperature and easy handling; survey of the temperature in individual tubes is possible, and the system is protected from water condensation and uncontrolled warming by the deep freezer. PMID- 1865241 TI - Dispermic fertilization of human oocytes. AB - Regardless of whether fertilization occurs in vivo or in vitro, polyspermic penetration of the human oocyte is a not infrequent cause of reproductive failure. This report describes the occurrence of human eggs fertilized by two spermatozoa and the variable developmental potentials expressed by the resultant embryos. The cellular and subcellular events that characterize the pronuclear and early cleavage stages of preimplantation embryogenesis are discussed with respect to the ability of such embryos to progress to implantation. PMID- 1865243 TI - An easy method for orientated embedding tissue culture cell monolayers in LR White resin for postembedding immunocytochemistry. AB - Partial polymerization of LR White resin blocks is a frequently encountered problem if oxygen is present during the polymerization reaction. Instructions are given for a simple method to embed cell culture monolayer in LR White acrylic resin, which is suitable for immunocytochemistry. The advantage of this method is that it is easy and reliable. It also ensures accurate orientation of the cell monolayer in relation to the desired plane of sectioning. PMID- 1865244 TI - Determination of vesicle size distributions by freeze-fracture electron microscopy. AB - The most common electron microscopic technique for obtaining information on size distributions of uncollapsed membrane vesicles is based on the method of van Venetie (1980). This technique involves the sizing of only those vesicles that were freeze fractured at their equatorial planes. As a result, only a small number of images can be used to generate size distributions. Further, the technique is susceptible to systematic error. An alternate approach is to consider the complete distribution of image sizes and use this distribution to determine the average size and distribution of the vesicles. It is shown that the mean vesicle size is 4/pi times the mean image size. As well, a parameter, m, which can be determined from the image distribution, can be used to characterize the vesicle distribution. The advantage of this new approach is that images of all vesicles are used, leading to a statistically better determination of vesicle sizes. PMID- 1865245 TI - Polychloroprene glue as an adhesive for mounting specimens for SEM. PMID- 1865247 TI - VDT exposure and pregnant workers. PMID- 1865246 TI - Improved fixation for cytochemical demonstration of acid phosphatase in mouse decidual cells. PMID- 1865248 TI - A comparison of cause-specific mortality among participants and nonparticipants in a work-site medical surveillance program. AB - Nonparticipants in general population health surveys have been found to be less healthy than participants, but data on nonparticipants in work-site health surveys have been more scarce. We compared cause-specific mortality among 11,156 male employees of The Dow Chemical Company who participated in at least one work site health examination between 1967 and 1978 with 6915 employees who did not participate. The nonparticipants experienced higher mortality rates for nearly every cause of death examined but particularly from smoking and alcohol-abuse related diseases. This was especially true during the first 5 years of follow-up, suggesting that some employees do not participate because they are already ill. These findings have important implications for the use of examination data for both primary and secondary disease prevention purposes, and these are discussed. PMID- 1865249 TI - Success in basic combat training: the role of cigarette smoking. AB - We studied whether cigarette smoking affected a soldier's ability to complete basic combat training. Demographic and tobacco use information was collected from a cohort of soldiers before they began training. A list of all graduates was obtained and analyzed against the initial questionnaire data. In this prospective study, the smoking group comprised 339 soldiers and the nonsmoking group comprised 535 soldiers. We found that those soldiers who smoked one or more packs of cigarettes per day were at a greater risk for failing basic combat training (relative risk = 2.05, P = 0.092. There was no relationship observed between a soldier's education and his ability to complete basic combat training. Our data indicate that smoking one or more packs of cigarettes per day may adversely affect a soldier's ability to complete basic combat training. PMID- 1865250 TI - Pulmonary health risks among northwest loggers. AB - Spirometry, respiratory symptom questionnaires, and chest radiographs were obtained from 688 loggers in Oregon and Washington. These were compared against previously published National Institute for Occupational Safety and Health studies of nonexposed blue-collar workers to determine if these predictions fit our population. The loggers forced expiratory volume in 1 second and forced vital capacity values were significantly greater than predicted, and their forced expiratory volume in 1 second/forced vital capacity values were less than predicted. The only consistent difference in symptoms between the sample and reference populations was for recent chest illnesses, which were more prevalent in the loggers than in the reference population. The chest radiographs showed a small excess of pleural thickening that we believe is most likely due to chest trauma. We conclude that the National Institute for Occupational Safety and Health studies spirometry prediction equations may not be generalized to other blue-collar populations. PMID- 1865251 TI - Correlates of motor-vehicle safety behaviors in working populations. AB - To determine the prevalence and correlates in a working population of failure to wear seat belts, drinking and driving, and speeding, we examined the responses of 18,046 health-profile participants. Twenty-four percent of subjects reported failure to wear seat belts at least 80% of the time. Twenty-two percent reported speeding at least 10 miles per hour over the speed limit when traffic permits. Twenty-three percent reported traveling at least once a month with a driver who had two or more drinks. Correlates of high-risk behaviors included male gender and youth. Educational attainment was inversely associated with seat-belt nonuse but directly related to speeding and drinking/driving. Our findings suggest a substantial opportunity to help employees lower important risks for serious motor vehicle injury. PMID- 1865253 TI - Poor agreement of occupational data between a hospital-based cancer registry and interview. AB - With occupation recognized as a risk factor for various cancers, collecting occupation and industry data by a number of vital registries, including cancer registries, has developed. Registries may be data sources for cancer etiology research and occupational disease surveillance, despite concerns that their data are fragmentary and may lack validity. To improve completeness and validity of occupational information in a hospital-based cancer registry, this study compared information obtained through abstracting medical records for the registry with information obtained through lung-cancer patient interviews. Employing the kappa statistic, agreement was generally poor, largely due to data missing in the medical record. Data quality of hospital-based cancer registries can be improved by employing trained cancer registrars to elicit occupational histories from patients. PMID- 1865252 TI - Lead exposure at uncovered outdoor firing ranges. AB - Excessive lead exposure in shooting instructors at indoor firing ranges and covered outdoor firing ranges has been documented. The City of Los Angeles assessed exposure of its full-time shooting instructors at uncovered outdoor ranges via air monitoring and blood lead-level measurements. Results of these tests revealed that significant lead exposure and absorption can occur at outdoor firing ranges. The use of copper-jacketed ammunition may decrease air lead levels and decrease lead absorption by range instructors. PMID- 1865254 TI - Ridge detection tactility deficits associated with carpal tunnel syndrome. AB - A ridge detection threshold task was administered to patients diagnosed as having carpal tunnel syndrome for studying performance in an occupationally relevant functional tactile inspection task. Thresholds were compared with a reference group of subjects not having carpal tunnel syndrome symptoms, performing the same task. The threshold detection task used the method of limits for studying the effects of carpal tunnel syndrome, rate of ridge height changes, ridge gradient, and direction of shearing against the skin on ridge detection thresholds for a repeated measures factorial experimental design. Sixteen carpal tunnel syndrome hands and 30 normal hands were studied. Average ridge detection threshold was 0.08 mm for the normal subjects and increased to 0.20 mm for the carpal tunnel syndrome subjects. No significant age effect was observed. These results suggest that workers having carpal tunnel syndrome may not detect an edge or surface defect in a tactile inspection task unless it was more than twice as high as detected by workers without CTS. PMID- 1865255 TI - Sick-hospital syndrome. AB - An outbreak of complaints consisting primarily of eye and respiratory tract irritation accompanied by headache, dizziness, fatigue, and nausea occurred among the operating room personnel of a large metropolitan hospital. This initially was attributed to infiltration of diesel exhaust emissions into the ventilation system. However, following correction of this problem and subsequent unrevealing air monitoring, symptoms persisted and were noted in personnel in adjacent areas of the hospital as well. An industrial hygiene and medical evaluation was undertaken. Monitoring for carbon monoxide, formaldehyde, and anesthetic gases and review of medical records and patient examinations were unrevealing, and the problem resolved gradually over several weeks. This outbreak represents a case of building-associated illness among health professionals in a hospital setting that was triggered by a single, identifiable noxious exposure but was sustained despite any apparent ongoing noxious exposures. PMID- 1865256 TI - Miracidia of Schistosoma japonicum: approach and attachment to the snail host. AB - Schistosoma japonicum miracidia swim directed along a chemical gradient toward the snails Oncomelania hupensis and Biomphalaria glabrata, and they turn back when the concentration of attractive chemicals decreases. The host signal for this chemotactic response has a molecular weight of more than 30,000. When swimming miracidia encounter the surface of O. hupensis or agar containing O. hupensis snail-conditioned water (SCW) they perform the host-specific responses "contact with return," "repeated investigation," and "attachment," but they do not exhibit such behavior when encountering B. glabrata surface or agar containing B. glabrata SCW. Thus S. japonicum miracidia respond to different host signals when they approach snails than when they attach to snails. PMID- 1865257 TI - Phaneropsolus spinicirrus n. sp. (Digenea: Lecithodendriidae), a human parasite in Thailand. AB - Phaneropsolus spinicirrus n. sp., collected in a postpraziquantel treatment stool of a 44-yr-old woman from Kalasin Province in northeastern Thailand, is described. It is the second species of the genus Phaneropsolus Looss, 1899, found to parasitize a human host. It differs from the first species, Phaneropsolus bonnei Lie, 1951, in the presence of a short spinose cirrus and the structure and distribution of tegumental spines. The new species is most similar to Phaneropsolus perodictici Goodman and Panesar, 1986, isolated from the potto, Perodicticus potto, in Uganda because digeneans of both species have numerous spines on the cirrus. However, the new species differs from P. perodictici in having more conspicuous spines, the genital pore at the posterior border of the oral sucker or lateral to the pharynx, a body and internal organs of larger size, conical spines on the tegument, an ovoid to bilobed ovary and a large V-shaped excretory bladder. Phaneropsolus spinicirrus is distinguishable from other previously reported Phaneropsolus by possessing a spinose cirrus. PMID- 1865258 TI - National seroprevalence of Toxoplasma gondii in pigs. AB - Serum samples from 11,842 commercial pigs killed in 1983-1984 throughout the United States were tested for anti-Toxoplasma gondii antibodies by the agglutination test in dilutions of 1:25, 1:50, and 1:500. Anti-T. gondii antibodies were found in 23.9% of pigs. At dilutions of 1:25, 1:50, and 1:500, 13.5%, 6.9%, and 3.5% were serologically positive, respectively. The prevalence of anti-T. gondii antibodies was higher in breeder pigs (42%) than in market pigs (23%). These results indicate that anti-T. gondii antibodies are widespread in the national swine herd. PMID- 1865260 TI - The component community structure of larval trematodes in the pulmonate snail Helisoma anceps. AB - Factors that affected the component community structure of larval trematodes in the pulmonate snail Helisoma anceps in Charlie's Pond, North Carolina, were studied over a 15-mo period using a multiple mark-recapture protocol. Patent infections of 8 species were observed in 1,485 of 4,899 snails examined. Reproductive activity, population size, and survival rate of the snail population were estimated to evaluate the extent of resource availability for the parasites. Antagonistic interactions between trematode species that occurred at the infracommunity level had a neglible effect on the composition and structure of the component community. The patterns observed at this level were related to temporal heterogeneity in the abundance of infective stages (mostly miracidia), differential responses of trematode species to the diverse and constantly changing distribution of snail size and abundance, differential mortality of snails infected with certain trematode species, constant recruitment of 1 trematode species over time, and the existence of predictable disturbances such as the complete mortality of the host population and recruitment of a replacement population during a 6-8 wk period. The last factor operated as a reset mechanism for this snail-trematode system once each year. A model of patch dynamics, with snails as patch resources, best explains the organization and dynamics of this system. PMID- 1865259 TI - Guild structure of larval trematodes in the snail Helisoma anceps: patterns and processes at the individual host level. AB - Factors that influenced the infracommunity structure of trematodes parasitizing the pulmonate snail Helisoma anceps were studied over a 15-mo period; the guild included 8 species of parasites. Infracommunities were depauperate, with double patent infections observed in only 7 of 1,485 infected snails; a total of 4,899 was examined. Halipegus occidualis-Haematoloechus longiplexus was the most common dual infection. Both species share the same definitive host and, in both cases, eggs are the infective stage for the snail. Switches and losses of infections in individual snails were observed, suggesting the occurrence of dynamic interactions within the guild. A dominance hierarchy was constructed based on field observations and experimental infections. Echinostomatids were dominant; species without rediae in their life cycles were subordinates. Halipegus occidualis (which has rediae) was intermediate in dominance. Spatial and temporal heterogeneity in the distribution and abundance of trematode infective stages indicate that not all the snails have the same probability of becoming infected. Habitat structure, behavior of the definitive host, the nature of the infective stages, and snail population dynamics (mortality, recruitment, and size structure) generated spatial and temporal heterogeneity in this system. As a consequence, predictions of the probabilities of interspecific interactions based on an analysis of observed and expected frequencies of multiple infections could be inappropriate unless the potential sources of heterogeneity are considered. PMID- 1865261 TI - The effects of periodic eutrophication on parasitism and stock identification of Trematomus bernacchii (Pisces: Nototheniidae) in McMurdo Sound, Antarctica. AB - McMurdo Sound, Antarctica, is suited for the study of the effects of eutrophication on diet-related parasites of Trematomus bernacchii (Boulenger, 1902) (Pisces). It has been relatively well studied, the environment is predictable, and there are significant differences in primary productivity over small distances. The differences in parasitism for 5 helminth species can be attributed to the enrichment processes in the sound. The prevalences of the acanthocephalan Echinorhynchus sp., the nematode Ascarophis nototheniae, the digenean Dinosoma sp., and the cestode Phyllobothrium sp. are significantly higher on the east side of the sound than on the west. The prevalence of the digenean Lepidepedon garrardi was significantly higher on the west side. We believe that the differences in the prevalences of infection between the east and west sides suggest that at least the benthic, adult fish do not readily move from one side of the sound to the other. We report the following (new host records are marked by asterisks): Echinorhynchus sp., Corynosoma hamanni (Acanthocephala); Phyllobothrium sp., Diphyllobothrium sp., Trypanorhyncha (Cestoidea); Clavellopsis (Copepoda); Dinosoma sp., Lepidepedon garrardi (Digenea); Pseudobenedenoides brachicola, Polyopisthocotylea (Monogenea); Contracaecum sp., Ascarophis nototheniae (Nematoda); Myxoproteus sp., Henneguya sp., Ceratomyxa sp., and Zschokkella sp. (Protozoa). PMID- 1865262 TI - Canine leishmaniasis: pathological and ecological factors influencing transmission of infection. AB - Canine leishmaniasis was studied in 1,823 dogs from the Lisbon metropolitan region. The breeds most affected were doberman and German shepherd, independent of sex and use. Young adult (12.2%) and older dogs (14.7%) had higher prevalences of infection. Parasitological confirmation of serological diagnosis was higher in dogs with indirect fluorescent antibody test titer greater than or equal to 1:512, indicating that parasitological patency is a late event. Exposure of Leishmania in lymph nodes is more efficient for parasitological confirmation (75.4% of cases). Frequent signs of disease were enlarged lymph nodes and onychogriphosis. However, 53.8% of the dogs with significant antibody titers (greater than or equal to 1:128) showed no symptom, suggesting that canine leishmaniasis has a prolonged asymptomatic period. This study confirmed the importance of the dog as the reservoir of visceral leishmaniasis. PMID- 1865263 TI - Infection of Aotus vociferans monkeys with different strains of Plasmodium falciparum. AB - Twenty-one splenectomized Aotus vociferans monkeys were infected with the different strains/clones of Plasmodium falciparum. Maximum parasitemia ranged from 1,302 to 1,460,000 parasites per mm3. Only the Santa Lucia strain was shown to produce gametocytes for extended periods. Gametocytes produced during the primary episode of parasitemia were highly infective to Anopheles freeborni mosquitoes. Gametocytes produced during recrudescence were not infective to mosquitoes feeding directly on the animals. This lack of mosquito infection during recrudescence periods suggests the presence of transmission-blocking immunity, which may be important in understanding the control of malaria through immunologic initiatives. PMID- 1865264 TI - Cultivation of excysted metacercariae of Echinostoma caproni (Trematoda) to ovigerous adults on the chick chorioallantois. AB - Excysted metacercariae of Echinostoma caproni were cultivated on the chick chorioallantoic membrane (CAM) maintained at 38.5 +/- 1 C and a relative humidity of 60-65%. Of 59 6-day-old embryos, each inoculated with 25 metacercariae, 29 (49.2%) were infected 2-12 days postinoculation. The total number of worms recovered from the infected eggs was 163 or 22.5% of the 725 inoculated metacercariae. Eggs contained from 1 to 12 (average 5.6) worms per CAM. Worm length increased rapidly from an average of 0.5 mm at 2 days to about 3.0 mm at 6 days postinoculation. Ovigerous worms first were seen on day 8 PI, but fluke eggs did not develop embryos. Worm development in ovo lagged about 1 day behind that of in vivo worms. One worm maintained for 17 days on 2 successive CAMs reached 6 mm in length, contained about 100 eggs in its uterus, and laid an additional 100 eggs on the CAM surface. PMID- 1865265 TI - Effects of medium alterations on in vitro development of Brugia malayi larvae in cultured mosquito thoraces. AB - A recent study showed that 1-day-old, intracellularly lodged larvae of Brugia species develop in vitro to the infective third-stage larvae (L3) in excised thoraces of susceptible mosquitoes in the diphasic insect tissue culture medium containing a nutrient agar base overlaid with a 1:1 mixture of Schneider's Drosophila medium and Grace's insect cell culture medium supplemented with 20% fetal bovine serum (FBS) and antimicrobial agents. In the present investigation, the diphasic culture medium was used to evaluate the effects of medium alterations on the development of 1-day-old, intracellularly lodged larvae of subperiodic Brugia malayi in excised thoraces of Aedes aegypti to the L3. One-day old larvae developed to the L3 in medium without nutrient agar base, at pH 7.0 and pH 7.5, in Hanks' balanced salt solution (HBSS) and in HBSS supplemented with bovine albumin fraction-V (BAF-V). These larvae also developed in the absence of FBS in the overlay medium, in overlay medium containing 5-20% FBS, in medium components obtained from different sources, in serum free Sf-900 (GIBCO) medium, and when FBS is replaced by BAF-V in the overlay medium. The percentage of L3 was not increased substantially in infected excised thoraces of mosquitoes when nutrient supplements, such as folic acid, p-aminobenzoic acid, glucose, lipid concentrate, hemin, or reduced glutathione, were added to the overlay medium containing BAF-V. These results suggested that 1-day-old, intracellularly lodged larvae developed to the L3 in infected excised thoraces of mosquitoes at almost the same rate as in intact mosquito, when excised thoraces were maintained alive under optimal conditions in a culture medium. PMID- 1865266 TI - Recovery, distribution, and development of Acanthocheilonema viteae third- and early fourth-stage larvae in adult jirds. AB - Living third- and fourth-stage larvae (L3 and L4) of Acanthocheilonema viteae were recovered quantitatively from adult Meriones unguiculatus within the first 10 days after subcutaneous inoculation of 60 arthropod-derived larvae (mL3). The average recovery of the inoculated larvae was about one third (28.5%), and the majority (87.7%) were found in muscular tissues. Seventy-two hours after inoculation, larvae could be isolated from all body locations, although the majority still was found near the site of inoculation. Morphological and biometrical data indicated that, at least until molting, the development of the larval population was not synchronous, with molting occurring over a period of 48 hr on days 7 and 8 postinoculation. The stomatal rings of postinvasive L3's and L4's were distinguishable structurally and could be used as stage-specific determinants. Immediately after infection, L3's showed a linear growth in diameter; rapid longitudinal growth started after the molt, leading to a doubling in the length of L4's within 4 days. The time course of shedding was reconstructed in detail using isolated L3/L4 intermediates. PMID- 1865267 TI - Species-specific differences in heterogonic development of serially transferred free-living generations of Strongyloides planiceps and Strongyloides stercoralis. AB - The direction of free-living development (homogonic vs. heterogonic) in Strongyloides stercoralis and Strongyloides planiceps was examined by successive transplantation of the uterine eggs of free-living females into a test tube culture system containing fresh feces. The eggs from the first-generation free living females of S. stercoralis did not develop into second-generation free living adult worms, but all developed into filariform larvae. However, the majority of S. planiceps eggs from the first-generation free-living females developed into second-generation free-living adults. By successive transfer of uterine eggs of each generation, 9 generations developed, and in every cycle more adult worms developed than filariform larvae. However, the number of free-living generations was not infinite; in experiments repeated twice, the number of worms developing from the eggs of eighth or ninth generations was too small to continue further culture. These findings indicate that the pattern of free-living development is different between the 2 species. PMID- 1865268 TI - Formation and excretion of calcareous bodies by the metacestode (Tetrathyridium) of Mesocestoides vogae. AB - The function of calcareous bodies, commonly found in the parenchyma of cestodes and trematodes, is relatively poorly understood. The present histochemical ultrastructural study of the proliferative tetrathyridia of Mesocestoides vogae revealed that calcareous corpuscles begin to form as organic (lipid-protein) masses that coalesce in parenchymal (calcareogenic) cells. Concentric accretion of organic and inorganic crystalline material then leads to the formation of typical refractile calcareous bodies. The precise composition of such bodies, determined by x-ray diffraction, revealed that their major inorganic constituent is indeed calcium, with significant amounts of phosphorus, silicon, and zinc as well. Emission of calcareous bodies through the tegument was observed by scanning electron microscopy, explaining their accumulation in the intracapsular spaces around worms embedded in liver tissue of the host. Following their emission, the crystalline substance of corpuscles dissolves, leaving only nonrefractile, membrane-bound cytoplasmic debris. These observations do not preclude the possibility that calcareous bodies may play some role as buffers or reservoirs of inorganic ions. However, it is difficult to accept such a function for unencapsulated worms in the coelom or intestinal lumen; we suggest that excretion is a more likely role in such sites. PMID- 1865269 TI - The cytoskeletal architecture of Trypanosoma brucei. AB - The cytoskeleton of Trypanosoma brucei has been analyzed by the high-resolution technique of quick-freeze deep-etch rotary-shadowing electron microscopy. The study provides detailed structural information on the subpellicular array of microtubules, the flagellum, and the interaction of these 2 major structures of the trypanosomal cytoskeleton with each other. The subpellicular microtubules closely interact both with the cell membrane and with each other. At the anterior tip of the cell they converge into a tightly closed structure, whereas at the posterior end the microtubular array remains open ended. The microtubular array is involved also in forming the opening of the flagellar pocket. The microtubular array interacts with the paraflagellar rod of the flagellum through a dense meshwork of fibers that are anchored on the microtubular surface with one end and within the paraflagellar rod structure with the other. The highly ordered, 3 dimensional network of the paraflagellar rod itself is connected tightly to the microtubular axoneme of the flagellum through a regular array of fleur-de-lis shaped linking structures. PMID- 1865270 TI - Surface ultrastructure of the developmental stages of Heterophyopsis continua (Trematoda: Heterophyidae). AB - Ultrastructural observations were made on the tegument of juvenile and adult stages of Heterophyopsis continua using scanning electron microscopy. On the surface posterior to the ventral sucker, the tegumental processes were bandlike in the metacercariae, cobblestonelike in the flukes 2 days postinfection (PI), and velvety at 3 days PI. The anterior surface between the oral and ventral suckers of the metacercariae was packed densely with tegumental spines having a 10- to 14-pointed tip. In flukes 6 days PI, the number of points increased to 15 17. The tegumental spines immediately behind the ventral sucker on the metacercariae surface possessed 5-7 points; posteriorly the points were reduced in size and in number. Ciliate sensory papillae (type I), as single or clumped forms of 2 or 3, were abundant around the oral and ventral suckers of metacercaria and adult worms. The clumped papillae appeared bilaterally symmetrical on the dorsal and ventral surfaces. The ciliate papillae may function in tango-, rheo-, and/or chemoreception. On the lip of the ventral sucker, 6-7 aciliate domed papillae (type II) were arranged in an equidistant manner. At 2 days PI each type II papilla became a clumped form having 2 or 3 papillae. Type II papillae may function as tango- and/or pressure-receptors. The structure and distribution of papillae suggest that the ventral sucker likely functions as a holdfast organ and the oral sucker as a probing organ involved in feeding. PMID- 1865271 TI - Concurrent infections with the ruminant nematodes Haemonchus contortus and Trichostrongylus colubriformis in jirds, Meriones unguiculatus, and use of this model for anthelmintic studies. AB - Haemonchus contortus- and Trichostrongylus colubriformis-infected jirds (Meriones unguiculatus) are useful for anthelmintic studies. With concurrent infections of these parasites established in the jird, questions of not only anthelmintic activity, but to some extent spectrum, could be assessed in a single model system. This report outlines a model using immunosuppressed (0.02% hydrocortisone in feed) jirds concurrently infected with H. contortus and T. colubriformis. Immunosuppressed jirds were inoculated with approximately 1,000 exsheathed infective larvae of each species, treated per os on day 10 postinoculation (PI), and killed on day 13 PI. Stomachs and small intestines were removed, opened longitudinally, incubated in distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for subsequent examination. Contents of both organs were examined using a stereomicroscope (15-45 x). Various standard anthelmintics were evaluated in the model; modern broad-spectrum ruminant anthelmintics (benzimidazoles, febantel, ivermectin, levamisole hydrochloride, and milbemycin D) are active uniformly and in most cases at doses comparable to those required for efficacy against these parasites in ruminants. This model, using worms of 2 genera living in distinct sites, allows preliminary evaluation of anthelmintic activity and spectrum for experimental compounds in a single cost and resource-efficient experiment. PMID- 1865272 TI - A simple method for cloning Giardia duodenalis from cultures and fecal samples. AB - Using a novel method for cloning Giardia duodenalis from cultures and fecal samples, 47 clones from 7 isolates were established in vitro. Average colony forming efficiency in established cultures was 43.2% compared to 11.2% when cloning directly from excystation. The highest success rate of cloning was found with the Portland (P1, ATCC No. 30888) isolate, with a colony-forming efficiency of 92.7%. Cloned and parent populations were compared over a range of 13 enzymes using starch gel electrophoresis. No genetic difference was found between any of the clones and the parent isolates. PMID- 1865273 TI - Altered adult worm location in young male jirds infected with Brugia pahangi. AB - Male jirds (Meriones unguiculatus) were inoculated subcutaneously with 100 Brugia pahangi L3 each at 2, 6, 10, and 15 wk of age to compare their susceptibility and pathologic reactivity to infection. Adult worm recoveries (mean +/- SD) ranged from 24.1 +/- 15.1 to 36.4 +/- 13.9 at 60 days postinfection. No significant difference in susceptibility was measured among the 4 age groups. Jirds infected at 2 wk of age had significantly fewer (alpha less than or equal to 0.025) testicular and intralymphatic worms than all other age groups. Numbers of intralymphatic thrombi were significantly lower (alpha less than or equal to 0.01) in jirds infected at 2 wk of age. Lymphatic lesion severity, expressed as the number of intralymphatic thrombi per intralymphatic worm, was similar between age groups. These data indicate no differences in susceptibility or lymphatic lesion formation following B. pahangi infection in 2-wk-old male jirds, despite altered adult worm location. PMID- 1865274 TI - The cell content of peritoneal exudates following the injection of neutral thiol protease into guinea pigs. AB - The cell content of the peritoneal exudate was examined 4 days after an intraperitoneal injection of glycogen in uninfected and Paragonimus westermani infected guinea pigs. In uninfected animals a reduction in macrophage count and an accumulation of granulocytes in the exudate were observed at 3 and 6 hr after an intraperitoneal injection of purified neutral thiol protease from P. westermani metacercariae. No such effect occurred after the enzyme was injected into infected animals. At 9 hr after enzyme injection, vacuoles were found in the cytoplasm of macrophages in uninfected animals. PMID- 1865275 TI - Infectivity, growth, and distribution of Echinostoma caproni (Trematoda) in the ICR mouse. AB - Host-parasite interactions of the intestinal trematode Echinostoma caproni were studied in ICR laboratory mice. All of 40 mice, each fed 25 metacercarial cysts of Echinostoma caproni, were infected 1-20 wk postinfection (PI) with a mean of 17.2 worms/host. At 24 and 29 wk PI only 2 of 6 mice (33%) were infected, with a mean of 4.2 worms/host. Mean body area of worms increased rapidly to about 5 mm2 by week 2, increased less rapidly to 8.8 mm2 by week 12, plateaued until week 24, and then declined. Mean dry weight of worms increased rapidly to about 0.5 mg by week 2, less rapidly to 1.4 mg by week 12, and then plateaued until week 24 PI. From 1 to 8 wk PI most worms localized in the jejunum and ileum; later most worms were in the jejunum and duodenum. Considerable differences were seen in the growth and distribution of E. caproni in the ICR mouse compared with previous studies on this echinostome species in the NMRI mouse. PMID- 1865276 TI - The controversy of the use of anti-gluten antibody (AGA) as a diagnostic tool in celiac disease. PMID- 1865277 TI - Alkaline gastroesophageal reflux in infancy. AB - Alkaline gastroesophageal reflux is a rare disorder, although it has been suggested as a cause of esophagitis. However, up to now, there exists no unequivocally accepted diagnostic method for alkaline reflux that can be routinely applied. "Normal ranges" of episodes of pH greater than 7.0-7.5 in asymptomatic as well as in symptomatic infants are proposed. In the asymptomatic infants (n = 83), the mean percentage of time the pH was greater than 7.0 was 1.3 +/- 2.6, and the number of episodes in 24 h with a pH greater than 7.0 was 10.4 +/- 16.4. In the symptomatic group (n = 60), including infants with chronic vomiting, the mean percentage of time the pH was greater than 7.0 was 0.15 +/- 0.5, and the number of episodes with a pH greater than 7.0 was 2.8 +/- 5.5. In all but six infants the percentage of time the pH was greater than 7.5 was less than 0.1. In three of four of these infants (endoscopy was refused by two parents) whose conditions exceeded the cut-off limits, there was a histologically proven esophagitis. To evaluate the proposed "normal" ranges for episodes of pH greater than 7.0 and 7.5, 200 symptomatic children were included in a prospective study. Symptoms were repetitive vomiting (n = 110), excessive crying (n = 53), and chronic respiratory disease (n = 37). Esophagoscopy was performed in 18 babies (9%) because pH monitoring data exceeded the proposed limits for the percentage of time the pH was greater than 7.0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865278 TI - Impaired intestinal function in symptomatic HIV infection. AB - A longitudinal (10-22 month) evaluation of intestinal symptoms and function was performed in five children with symptomatic human immunodeficiency virus (HIV) infection. All received cotrimoxazole, ketoconazole, and immunoglobulins. A search for enteric pathogens and intestinal function tests were repeatedly performed in all patients. Mild episodes of diarrhea were observed in two children. One had cow's milk protein intolerance. Giardia lamblia was found in an asymptomatic carrier. Evidence for impaired intestinal function was found in all patients. These consisted of positive D-xylose and iron oral loads, increased steatorrhea, increased fecal excretion of alpha 1-antitrypsin, abnormal intestinal permeability, and increased food antibody levels. Our results suggest that severe diarrhea may be uncommon in children with HIV infection receiving antimicrobial prophylaxis, but that the intestinal function is frequently, and often markedly, impaired. PMID- 1865279 TI - Serum lipids in celiac children. AB - The plasma lipid levels were investigated in 45 celiac children under 3 years of age and 49 over this age at diagnosis (untreated groups), after gluten-free diet and in comparison with irritable bowel syndrome (IBS) groups matched for size, gender, and age. Total and HDL cholesterol levels were significantly lower and triglycerides higher in celiac untreated children than in IBS control children in both age groups. HDL cholesterol significantly increased in both age groups after some months of gluten-free diet. Total and LDL cholesterol significantly increased and triglycerides decreased in the younger group of subjects after the period of gluten-free diet. These results may be useful for diagnostic purposes and to motivate a strict gluten-free diet in celiac children. PMID- 1865280 TI - Alanine-based oral rehydration solution: assessment of efficacy in acute noncholera diarrhea among children. AB - This randomized, double-blind trial determined whether adding 90 mmol/L of alanine with a reduction in glucose to 90 mmol/L (alanine ORS) improves the efficacy of the standard oral rehydration solution (WHO-ORS). One hundred twenty nine males aged 3-48 months with weight for length greater than or equal to 70% of NCHS, diarrheal duration less than or equal to 96 h, and clinical signs of mild to moderate dehydration were randomly allocated to either treatment group. During 0-6 h of treatment, ORS was offered at 120 ml/kg for rehydration without food or water. Beyond 6 h, ORS was offered as a volume-to-volume replacement for stool losses and a mixed diet of uniform composition was offered in amounts standardized for body weight. The most frequently isolated pathogens in alanine ORS and WHO-ORS groups were rotavirus (42 and 48%, respectively) and enterotoxigenic Escherichia coli (15 and 12%, respectively). In the 0-6 h period when food was withheld, median urine output in ml/kg (8;5, p less than 0.05) and percentage decrease in total serum solids (9:7%, p = 0.06) was significantly greater in alanine ORS than in WHO-ORS; median ORS intake and stool output were marginally lower in the alanine group but the differences were statistically not significant. Between 0 h and recovery, although the median values for duration of diarrhea (56.5 and 65.0 h), ORS consumption (260 and 323 ml/kg), and stool output (188.4 and 216.3 g/kg) were lower in the alanine ORS group, these differences with the WHO-ORS group were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865281 TI - Stable isotopic measurement of endogenous fecal calcium excretion in children. AB - Using a stable isotopic technique in which 42Ca was administered via a bolus injection, we measured endogenous fecal calcium excretion, Vf, in five healthy children, aged 3-14 years. The Vf averaged 1.4 +/- 0.4 mg/kg/day, and was lower than urinary Ca excretion (Vu) in four of the five children. These results for Vf are consistent with previously reported results for Vf in healthy adults and much lower than those reported in premature infants. These results may be useful in understanding developmental changes in Ca metabolism and in interpreting dual tracer Ca isotope studies in children. PMID- 1865282 TI - Affinity chromatographic identification and quantitation of blood group A-active oligosaccharides in human milk and feces of breast-fed infants. AB - The finding of large quantities of blood group A-active oligosaccharides in the feces of a blood group A breast-fed infant motivated a search for the origin of these compounds. Using an affinity chromatographic technique, the nature of A active oligosaccharides in human milk is demonstrated. The amounts of A-active tetrasaccharide (A-tetra) and the Lewis b-active lacto-N-difucohexaose I (LND-I) varied between 19-375 mg/L for A-tetra and 14-710 mg/L for LND-I. Using the same technique, the amounts of A-tetra and LND-I in milk samples from five women of different blood groups were compared with those in the feces of their breast-fed infants. The A-tetra was present only in feces from infants of blood group A or AB mothers and the amount per 24 h corresponded roughly to that in a I-L portion of milk. One of the milk samples was also analyzed for the presence of larger A active oligosaccharides (A-pentasaccharide, A-hexasaccharide, and A heptasaccharide). Their amounts were much less as compared to the amounts present in feces. These results indicate that milk is a possible source for the smallest A-tetrasaccharide found in the feces of breast-fed infants, while the larger A active oligosaccharides might be the result of an intestinal metabolic modification. PMID- 1865283 TI - Sialylated oligosaccharides in human milk and feces of preterm, full-term, and weaning infants. AB - The amount of free and glycosidically bound sialic acid was quantitated in the oligosaccharide fraction of breast milk from nine women in the 2nd-3rd week of lactation. These amounts showed a certain individual variation but the amount of bound sialic acid was higher than the free sialic acid in each sample. A similar study on the feces from preterm and full-term breast-fed infants revealed that the amount of free sialic acid increased while the bound sialic acid decreased during maturation, which could possibly be a result of increasing activity of an intestinal sialidase in the newborn child. The fecal oligosaccharide patterns in one blood group A secretor breast-fed infant were studied every 2 months during weaning until the age of 1 year. It was seen that the fecal oligosaccharide pattern disappears, along with the blood group A-active compounds, with a corresponding decrease in the amount of breast milk in the diet. PMID- 1865284 TI - Comparison of nonabsorbable markers Poly R-478 and [14C]PEG-4,000 for use in developmental absorption studies. AB - To determine the utility of Poly R-478, a stable, polymeric dye (MW, 40,000), as a nonabsorbable marker for studies in the developing small intestine, it was validated by comparison to carbon 14-labeled polyethylene glycol, MW 4,000 [( 14C]PEG-4,000) in rats from 14 to 40 days of age. The recovery and quantification of Poly R-478 from biological samples is simple and rapid compared to other nonradioactive nonabsorbable markers. In 40-day-old rats simultaneously given Poly R-478 and [14C]PEG, total recoveries were similar, the percentages of the Poly R-478 dose and the [14C]PEG dose recovered per segment were identical, and taurocholate absorption rates calculated using each marker were comparable. Recovery of Poly R-478 from flushed intestinal segments, determined by a one-step extraction, was equivalent to that of [14C]PEG in 40-day-old rats (96.5 +/- 3.7% versus 102.7 +/- 10.1%; NS) but was superior to that of [14C]PEG in 21-day-old rats (98.0 +/- 6.2% versus 63.4 +/- 5.5%; p less than 0.001) and 14-day-old rats (97.8 +/- 6.7% versus 56.7 +/- 12.6%; p less than 0.001). Within each age group, the distribution of Poly R-478 within the intestine was similar to that of [14C]PEG. In addition, total taurocholate absorption in the presence of Poly R 478 was comparable to that in the presence of [14C]PEG. Complete recovery of Poly R-478 from a suspension of liver particles and from mixtures with two commercial infant formulas was demonstrated in vitro, suggesting that Poly R-478 may be used when foods are present in the intestine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865285 TI - Effect of cholesterol deprivation on piglet small intestine and serum lipids. AB - Using the neonatal piglet, the effects of dietary cholesterol deprivation on growth, intestinal enzyme activity, intestinal and hepatic 3-hydroxy-3 methylglutaryl-coenzyme A reductase (HMG-CoA reductase), and serum lipid were studied. Six litters of piglets were randomly assigned to one of two feeding regimens: restricted (800 ml of formula/24 h) versus unrestricted (1,200 ml of formula/24 h). Within litters, piglets were separated by sex, then randomly assigned to a formula containing low cholesterol (less than 2 mg/dl) or high cholesterol (145 mg/dl). Piglets were fed for 2 weeks. Male piglets in the restricted low cholesterol group gained significantly less weight per milliliter of formula than the restricted high cholesterol males. No effect was observed in the females. Microvillus membrane lactase activity was greater in males fed a high versus low cholesterol diet. Intestinal and hepatic HMG-CoA reductase activities and serum lipid profiles showed a trend toward compensation for dietary cholesterol deprivation but did not differ statistically between the cholesterol-fed versus -deprived groups. It is concluded that dietary cholesterol deprivation in the male neonatal pig causes alterations in growth, but no other statistically significant responses were detectable in this study. PMID- 1865287 TI - Needed: a research agenda for PNPs. PMID- 1865286 TI - Nondairy-creamer-induced kwashiorkor: 5-year follow-up. AB - Failure to thrive may not be a result of organ disease, physical abuse, or intentional neglect. We describe an infant who developed kwashiorkor with a high fat, low-protein, nondairy coffee creamer diet. The elimination diet was administered on the advice of a family friend for a facial rash. The child presented at 10 months of age with decreased weight for height, rash, hepatomegaly, edema, hypoproteinemia, hypoalbuminemia, anemia, hypoglycemia, and evidence of hepatic sequestration of lipids. A rapid recovery of biochemical abnormalities was evident on reinstitution of a full diet. An intellectual assessment at age 5 years showed normal results. PMID- 1865288 TI - Case management: ambiguous at best. AB - This article defines case management with an emphasis on the functions and providers of various case management models. Nursing Case Management delivery system is compared with several other models of case management. The potential role for the nurse practitioner in case management is discussed as well as ethical pitfalls that are attributed to various case management models. PMID- 1865289 TI - Office management of the infant with colic. AB - Coping with a colicky infant can be stressful for parents. Proper office management can reduce parental stress and help parents handle the prolonged crying periods. This article assists the practitioner to better define colic and the current "cures" for excessive crying. Office management is reviewed, focusing on calming techniques and psychosocial support for parents and family. A case study is reviewed, and the use of appropriate referrals is discussed. PMID- 1865290 TI - Biting in day care centers: incidence, prevention, and intervention. AB - Analysis of accident logs in child day care centers indicates that biting is common, especially among toddlers 13 to 30 months of age. Children of this age often lack appropriate verbal skills and resort to aggressive means to achieve their goals. Still awkward in gross-motor skills, toddlers can also suffer self bites following accidental falls. According to medical reports, human bites sometimes are more virulent than animal bites and can cause severe trauma. Although the AIDS virus has been cultured from saliva, transmission from saliva alone has not been documented. Bite injuries in day care, however, usually are minor and can be treated by washing, applying cold compresses, and comforting the child. Suggested methods to diminish the frequency of biting in day care include physical changes within the room, behavior modification, and other classroom management techniques. PMID- 1865291 TI - Menstrual disorders during adolescence. AB - Concerns about menstrual function are a frequent reason for primary care visits during adolescence. Following a review of normal pubertal development and menstrual function, primary care assessment and management of delayed menarche, amenorrhea, and dysfunctional uterine bleeding during adolescence are presented. PMID- 1865292 TI - Anticipatory guidance for the employed breast-feeding mother. AB - A significant number of women are combining childrearing and career. Mothers who opt to breast-feed while employed may demonstrate increased breast-feeding success when supported by knowledgeable counseling. This article discusses specific techniques for maintaining maternal fluid intake; pumping, storing and preparing breast milk; wardrobe planning; and personal hygiene. Knowledge of these measures will provide the basis for anticipatory guidance for mothers who wish to balance the demands of breast-feeding and employment. PMID- 1865293 TI - Assessment of hyperbilirubinemia in full-term infants: Part II. AB - The nurse practitioner plays an important role in assessing infants for factors that may contribute to unconjugated bilirubinemia. Healthy, full-term infants with unconjugated hyperbilirubinemia and no evidence of hemolysis require monitoring of their total serum bilirubin levels and stooling patterns, and they need encouragement to feed more frequently to resolve the hyperbilirubinemia. Promoting frequent breast-feeding is essential, especially for infants with unconjugated hyperbilirubinemia. For those infants with evidence of hemolysis or exaggerated physiologic jaundice, more advanced medical intervention such as phototherapy and exchange transfusion are available when indicated. PMID- 1865295 TI - Pertussis in an infant. PMID- 1865294 TI - Delayed sexual development. AB - Sexual maturation can occur at an early age, at the expected or average time, or late. In adolescents who mature late, osseous development may be delayed. A variety of causes for delayed growth and sexual development should be evaluated. Constitutional delay is a nonpathogenic variation within normal growth parameters. The Tanner criteria should be used in assessing sexual maturation and bone age evaluation for skeletal growth. These criteria are based on the fact that sexual growth follows predictable patterns. Children need reassurance about their developmental growth, and subsequent growth should be monitored carefully. PMID- 1865296 TI - Treatment of Rocky Mountain spotted fever. PMID- 1865297 TI - 8-year-old girl with short stature. PMID- 1865298 TI - Medicaid reimbursement and pediatric nurse practitioners. PMID- 1865299 TI - Assessment of ego functioning in multiple personality disorder. AB - The dissociative disorder known as multiple personality disorder (MPD) presents a diagnostic challenge to psychological assessment techniques. A case example is presented in which a new self-report, multifactorial measure of ego functioning discriminated distinct profiles for four personalities within one multiple personality organization. Interpretations of characteristics of the primary and secondary personalities based on the Bell Object Relations Reality Testing Inventory (BORRTI) are presented. The relationship between these findings and other approaches to psychological testing for dissociation and MPD are discussed. It is suggested that this approach will facilitate the clinical assessment of suspected MPD subjects and contribute to affording appropriate treatment to this population. PMID- 1865300 TI - Toward the equivalence of the HIT and HIT 25 in community-residing older adults. AB - In a study by the first author wherein 102 community-residing older adults were administered the Holtzman Inkblot Technique (HIT), data collected were analyzed regarding the equivalence of the HIT and the HIT 25. Although alpha coefficients and split-half correlations were low when single-response-per-card data were analyzed, corrected Spearman-Brown coefficients were more supportive of the use of the HIT 25 with older adults. These data suggest that although a shortened form of the HIT may be useful with aged persons, research exploring the substantive bases for creating a shortened version of the HIT is nevertheless necessary. PMID- 1865301 TI - The Color-A-Person Body Dissatisfaction Test: stability, internal consistency, validity, and factor structure. AB - Stability, internal consistency, validity, and factor structure of the Color-A Person Body Dissatisfaction Test (CAPT) were assessed. Two- and 4-week test retest correlations for college students and alpha coefficients for students and eating-disorder patients ranged from .70 to .89. Factor structure was unaffected by gender and clinical status. Correlations were mostly between -.40 and -.60 with Rosenberg's (1965) Self-Esteem Scale and Secord and Jourard's (1953) Body Cathexis Scale (BCS). Men higher on Body Mass Index (BMI) liked upper body parts; women higher on BMI disliked lower body parts. Treatment for bulimia affected both body image tests comparably. PMID- 1865302 TI - The factor analytic structure of the Roberts Apperception Test for Children: a comparison of the standardization sample with a sample of chronically ill children. AB - A confirmatory principal component factor analysis of the Roberts Apperception Test for Children was conducted using the standardization sample and a sample of chronically ill children. An interpretation of three- and four-factor solutions identified the three-factor solution as superior to the four-factor solution as measured by chi-square goodness of fit and coefficients of convergence. A cluster analysis using Ward's minimum variance method was calculated to determine the typical profiles that best describe the chronically ill sample. Results of this analysis reveal two distinct profiles that differ primarily on the level of adaptive psychological functioning. PMID- 1865303 TI - What have surveys taught us about the teaching and practice of psychological assessment? AB - In efforts to gather information about training in and the practice of psychological assessment, numerous surveys of practicing psychologists, training program directors, and internship training directors have been conducted. In this article, I briefly review all survey studies about psychological assessment that have appeared in the last 30 years (1960 through early 1990). The major findings of all the surveys are summarized in 14 points, and discussion of several of the points is provided. Of most significance, the surveys collectively attest to (a) the remarkable stability of psychologists' assessment practices over the past 3 decades; (b) the ever-consistent, ever-continuing significance of the assessment role in psychological training and practice; and (c) the resilient, enduring nature of projective techniques in psychodiagnostic assessment. PMID- 1865304 TI - Hostility, aggression, and anxiety levels of divorce and nondivorce children as manifested in their responses to projective tests. AB - The effects of parental divorce on the levels of aggression, hostility, and anxiety in children, as measured by the Rorschach test, together with the type and direction of aggression, as measured by the Rosenzweig Picture-Frustration (P F) Study, were studied. The Rorschach and the Rosenzweig P-F study were administered to a nonclinical sample of 108 Swedish children ranging in age from 10 to 12 years old. The subjects constituted a divorce and a nondivorce group of 27 girls and 27 boys each. Children of divorced parents (hereafter referred to as divorce children, divorce boys, or divorce girls) showed significantly higher levels of hostility, aggression, and anxiety than children of married parents (hereafter referred to as nondivorce children, nondivorce boys, nondivorce girls). There were significant differences found in the type and direction of aggression between divorce girls and boys. Divorce boys showed more extraggression and ego defensive reactions, whereas divorce girls tended to evade aggression. The differences between divorce and nondivorce groups and the diversity of reactions between divorce boys and girls are discussed. PMID- 1865305 TI - MCMI-II report style and bias: profile and validity scales analyses. AB - This study examines the behavior of the Millon Clinical Multiaxial Inventory-II (MCMI-II) in the face of various response styles and biases. The profiles and validity configurations of eight different test-taking styles were analyzed. Four hundred MCMI-II inventories (50 for each of the following categories) were administered or generated to produce the following: (a) normal endorsement by subjects, (b) fake good for administrative reasons, (c) fake good for clinical reasons, (d) fake bad administratively, (e) fake bad clinically, (f) 50% true/50% false computer generated, (g) 95% true computer generated, and (h) 95% false computer generated. Good statistical and clinically relevant separation of the profiles was found for normal, fake good, fake bad, and the randomly generated profiles with 44% of the variance predicted. The percentage of profiles identified by validity scales, however, was modest. PMID- 1865306 TI - The MCMI-II depression scales: do they assist in the differential prediction of depressive disorders? AB - This study examined the diagnostic efficiency of the Millon Clinical Multiaxial Inventory-II (MCMI-II) Major Depression (CC) and Dysthymia (D) scales for the differential prediction of unipolar depressive disorders. The MCMI-II was administered to 109 inpatients at a large private psychiatric hospital in the Midwest. All patients had a primary Axis I diagnosis of a depressive disorder, given at discharge by the attending psychiatrists. When CC scores were compared to clinician diagnoses, results indicated that the sensitivity of the CC scale was improved over what had previously been reported for studies involving the MCMI-I CC scale. However, overall, the D scale functioned slightly better as a predictor of major depression than did the CC scale. One likely factor in explaining this finding is that the CC scale contains very few items assessing vegetative/somatic symptomatology, which are the critical factors in distinguishing major depression from other unipolar depressive disorders. PMID- 1865307 TI - The Ego Impairment Index as a predictor of outcome in melancholic depressed patients treated with tricyclic antidepressants. AB - The standard model of assessing ego impairment relies on patients' accurate self report and description of their behavior. This study offers an alternative approach to assessing ego impairment in a population of major depression, melancholic type outpatients treated with tricyclic antidepressants. A new index called the Ego Impairment Index (EII) was developed. The index is derived from the Rorschach test and offers a single composite score of ego impairment. It was hypothesized that those melancholic, biologically depressed individuals who were lacking in ego resources were less likely to benefit from tricyclic antidepressant treatment. Thus, the EII could predict overall outcome while on antidepressants. The results support that the level of ego impairment, as assessed by the EII, could predict depression outcome averaged over 9 weeks of tricyclic antidepressant treatment. PMID- 1865308 TI - Measures of depressive dimensions: are they interchangeable? AB - Several theorists have posited two focuses for depressive experience and/or vulnerability: dependency and rejection, and self-criticism and failure. In turn, three instruments have emerged, each addressing these two components, respectively: the Depressive Experiences Questionnaire (DEQ; Dependent and Self Critical scales), the Sociotropy-Autonomy Scales (SAS), and the Anaclitic and Introjective Dysfunctional Attitude Scales (DAS). In this study, we addressed the relations within and among these three pairs of scales in a large undergraduate sample. Generally, the DEQ-Dependent, SAS-Sociotrophy, and DAS-Anaclitic scales showed substantial convergent and discriminant validity. Although this was true also for the DEQ-Self-Critical and DAS-Introjective scales, neither scale was closely related to the SAS-Autonomy scale, which appeared instead to be a better measure of counter dependency than a measure of self-critical, introjective features. PMID- 1865309 TI - Development and validation of the Physical Appearance Related Teasing Scale. AB - The development and preliminary validation of the Physical Appearance Related Testing Scale (PARTS) is reported. The 18-item scale has good psychometric qualities (high internal consistency and test-retest reliabilities) and consists of two factors: Weight/Size Testing (W/ST) and General Appearance Teasing (GAT). The W/ST converges well with measures of eating disturbance, body image dissatisfaction, social comparison, depression, and self-esteem, whereas the GAT scale shows little relationship to these variables. The role of teasing history as an etiological component of body image and eating disturbance is discussed; the need for further validation work on the PARTS is addressed. PMID- 1865310 TI - Subtle-obvious scales of the MMPI: indicators of profile validity in a psychiatric population. AB - This study explored the usefulness of the Minnesota Multiphasic Personality Inventory (MMPI) Subtle-Obvious scales as profile validity indicators with a inpatient psychiatric population. Some 292 MMPI profiles were utilized and divided into overreporters, underreporters, and standard reporters, based on their Subtle-Obvious scale scores. Reporting style was shown to be unrelated to actual patient pathology because of the lack of relationship between reporting style and diagnostic categorization according to the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. [DSM-III-R]; American Psychiatric Association, 1987) Axis I and II. Comparisons of MMPI profiles of the three groups revealed that overreporters endorsed more pathology on the MMPI clinical scales than did either underreporters or standard reporters. The same pattern of response style was demonstrated by subjects on another objective measure, the Beck Depression Inventory, whereas on a projective measure, the Rorschach Inkblot Test, there were no differences between groups. These findings suggest that clinicians may want to utilize the Subtle-Obvious scales to gain information about MMPI profile validity. Specifically, profiles of patients identified as overreporters should be interpreted with caution so as to not overstate their level of pathology. PMID- 1865311 TI - Cardiovascular risk factors in children: a Bloomsday research report. AB - Cardiovascular risk factors identified in major studies of children include a family history of heart disease, smoking, blood pressure, dietary factors, exercise or fitness level, and stress. The purpose of this descriptive study was to identify differences in children's physical measurements with regard to six cardiovascular risk factors. A descriptive design using three questionnaires and physical measurements was used. The questionnaires included the Bloomsday Cardiovascular Fitness Questionnaire, the Coronary Risk Profile, and the Diet Habit Survey. Physical measurements included blood pressure readings, weight, total serum cholesterol, and high-density lipoprotein levels. A convenience sample of 78, predominantly Caucasian children between the ages of 7 and 18 years (M = 13.13, SD = 2.79) participated. Results indicated that differences in physical measurements were significantly for children with respect to the cardiovascular risk factors, including dietary factors, blood pressure, exercise, and stress. Nursing implications for thorough assessment and intervention through education are discussed. PMID- 1865312 TI - Cognitive abilities of preschool children: implications for nurses working with young children. AB - To effectively care for well or ill children, nurses must know something about how children think and what they are capable of comprehending. Nurses have traditionally based assumptions about children's cognitive abilities on a surface knowledge of Piaget's theory of cognitive development. Many recent researchers in the field of cognitive development have pointed out limitations in Piaget's theory and offer new ways of conceptualizing the way children think. In this article, I will identify limitations of Piaget's theory as it applies to preschool-aged children. Ideas of researchers using an information processing approach to understanding children's thinking will be described as alternative approaches to the understanding of preschool thought. I prescriptively postulate how research findings concerning cognition have implications for nurses working with young children. PMID- 1865313 TI - Growth-enhancing interventions for nonorganic failure to thrive. AB - The purpose of the study was to determine the effect of two interventions, Calorie Management and Socioemotional Growth Fostering, on (a) the weight of children aged 1 to 3 years with nonorganic failure to thrive and (b) the interaction behaviors of 10 mother-child dyads. Calorie Management, focusing on nutritional intake, seemed to enhance current mother-child conflicts. The Socioemotional Growth Fostering Intervention, focusing on healthy mother-child interaction behaviors, produced a greater weight gain in the children and growth enhancing behaviors in the mothers. PMID- 1865314 TI - Systemic lupus erythematosus in adolescents. AB - Once considered a rare, fatal illness in children and adolescents, systemic lupus erythematosus (SLE), or lupus, is now understood to be a relatively common chronic disorder in these age groups. This article provides a brief overview of the disease, describing its etiology, pathology, clinical manifestations, diagnosis, and treatment. A case history of an adolescent girl with lupus is presented, and the role of the nurse is discussed in relation to promoting four developmental tasks of adolescents: developing a positive body image, establishing a sexual identity, achieving independence, and acquiring formal thought processes. Since lupus interferes to some degree in the accomplishment of these tasks, we suggest methods of assessment and intervention that the nurse can use in each area to overcome these interferences. PMID- 1865315 TI - Understanding the child with special health care needs: a developmental perspective. AB - Children with special health care needs and their families are becoming a greater part of pediatric nursing practice, and often present with major health and psychosocial needs that interfere with their ability to function. Optimal intervention with these children requires an understanding of their chronic conditions as well as their unique developmental needs. This paper reviews the characteristics of children with special health care needs and introduces some of the most salient theories of child development in order to provide a perspective from which to view this population. A case example that illustrates some of the features discussed is presented. Because a knowledge of theories of child development can improve the care provided to children with special health care needs, it should be included as part of nursing curricula. PMID- 1865316 TI - A comparison of fathers of high-risk newborns and fathers of healthy newborns. AB - Eighteen fathers of healthy newborns were matched and compared with 18 fathers of newborns with health problems at birth to determine if there is a relationship between the newborn's health status and paternal perceptions, behaviors, and adjustment to fatherhood. A series of questionnaires were administered during the newborn's hospitalization and at 1 and 3 months after discharge. Fathers of newborns with health problems performed significantly more infant care (p less than 0.005) behaviors and were found to have higher adjustment to parenthood scores (p less than 0.0381) 1 month after discharge than fathers of healthy newborns. No differences were found between the two groups 3 months after discharge. PMID- 1865317 TI - Research subjects: yours, mine, or ours? AB - Involving staff in research will improve communication and heighten interest of nurses in research. Hopefully, this sharing will result in more research questions to be asked by researchers than are relevant to clinical practice. Also, sharing will encourage and facilitate the development of research-based practice and contribute to more varied and skilled research teams. Such collaborative activities between clinicians and nurses will further acquaint each group with the other's world and ultimately improve patient care and expand nursing science. Ultimately, these relationships will increase researchers' investment in clinical care and clinicians' research savvy and confidence. PMID- 1865318 TI - Part of me died with you. PMID- 1865319 TI - Project Head Start: "an extraordinary economic buy". PMID- 1865320 TI - Evaluation of a new infrared tympanic thermometer: a comparison of three bands. AB - As technology advances, it is important for nurses to compare various types of equipment used on pediatric patients to determine the cost effectiveness, risk, and ease of use. Presently, there are several types of electronic thermometers in use to measure body temperature. The following article discusses the comparison of the Thermoscan Instant Thermometer (Thermoscan Inc., San Diego, CA) with the First Temp infrared (Intelligent Medical Systems, Carlsbad, CA) and IVAC electronic thermometer (IVAC Corporation, San Diego, CA). PMID- 1865321 TI - An educational challenge: focus on behavior. PMID- 1865322 TI - The care of children with minimal brain dysfunction: a Roy adaptation analysis. PMID- 1865323 TI - Sharing of home responsibilities between professionally employed women and their husbands. AB - A sample of 139 married couples with young children and with relatively equal status careers (wives were university professors or businesswomen) were interviewed about work and home life. Considerable, traditional inequity in the distribution of child-care tasks and chore responsibility was noted, but women were generally satisfied with their husbands' home involvement. In the academic sample, the longer hours each spouse worked, the more child care the other performed; in the business sample, child-care involvement was largely determined by the husband's work hours, income, and education. Overall, women were more self critical than were men about their performance in home roles, and women's role performance was rated more highly by husbands than by themselves. Women professionals' continued use of traditional sex role standards and the importance of attending to both partners' perspectives in studies of married life are discussed. PMID- 1865324 TI - Attachment in marriage: effects of security and accuracy of working models. AB - Working models of attachment in marital functioning were examined. The security and accuracy of working models were measured with a new Q-sort method. Spouses with secure working models (self as relying on partner and partner as psychologically available) showed more constructive modulation of emotion and reported better marital adjustment. The accuracy of internal working models, measured with an objective index of spouses' agreement about models, was associated with independent reports of marital adjustment and observers' ratings of communication in problem-solving and confiding tasks. Behavior in communication tasks showed predictable associations with attachment security. Husbands' attachment security covaried with wives' rejection during problem solving, and wives' security covaried with quality of husbands' listening during a confiding task. A reciprocal interaction view of working models and marital functioning is supported. PMID- 1865325 TI - Individual differences in sociosexuality: evidence for convergent and discriminant validity. AB - Individual differences in willingness to engage in uncommitted sexual relations were investigated in 6 studies. In Study 1, a 5-item Sociosexual Orientation Inventory (SOI) was developed. Studies 2, 3, and 4 provided convergent validity evidence for the SOI, revealing that persons who have an unrestricted sociosexual orientation tend to (a) engage in sex at an earlier point in their relationships, (b) engage in sex with more than 1 partner at a time, and (c) be involved in relationships characterized by less investment, commitment, love, and dependency. Study 5 provided discriminant validity for the SOI, revealing that it does not covary appreciably with a good marker of sex drive. Study 6 demonstrated that the SOI correlates negligibly with measures of sexual satisfaction, anxiety, and guilt. The possible stability of, origins of, and motivational bases underlying individual differences in sociosexuality are discussed. PMID- 1865326 TI - Predicting personality and behavior: a boundary on the acquaintanceship effect. AB - Recent research has shown that interjudge agreement in personality ratings increases with acquaintanceship. The present study sought to replicate and extend this finding by investigating the relation between acquaintanceship and behavioral prediction. A total of 138 undergraduate targets were videotaped while interacting with an opposite-sex partner in 3 situations. The targets also completed 5 personality measures. Results indicated that acquaintances' judgments predicted personality scores much better than did strangers' judgments, but acquaintances' and strangers' judgments did equally well at predicting behavior. Implications for research on the accuracy of personality judgments are discussed. PMID- 1865327 TI - Multidimensionality of state and trait anxiety: factor structure of the Endler Multidimensional Anxiety Scales. AB - The Endler Multidimensional Anxiety Scales (EMAS) are derived from an interactional model of personality that proposes that anxiety is a function of the interaction of person and situation variables. The EMAS distinguish between state and trait anxiety and assume that both are multidimensional constructs. The EMAS were administered to 2,009 students in a neutral situation. Three factor analyses were performed to clarify the empirical relation between state and trait anxiety and the variables within the 2 domains. Results support the distinction between state and trait anxiety. Factor analysis of the state items provided support for the separate dimensions of cognitive and autonomic state anxiety. Factor analysis of the trait items provided support for trait anxiety multidimensionality. Four congruent factors were associated with increases in state anxiety in 4 general situations: Social Evaluation, Physical Danger, Ambiguous, and Daily Routines. PMID- 1865328 TI - Microbial models of mammalian metabolism: production of 3'-hydroxywarfarin, a new metabolite of warfarin using Cunninghamella elegans. AB - Warfarin, an anticoagulant and "metabolic probe" for cytochrome P-450 isozyme multiplicity, was metabolized by the fungus Cunninghamella elegans (ATCC 36112) to yield the previously unreported metabolite 3'-hydroxywarfarin. This metabolite was isolated from cell suspension cultures and characterized by analytical (HPLC) and spectral (EI-MS, PMR) comparisons with synthetic 3'-hydroxywarfarin. PMID- 1865329 TI - Pharmacokinetics of acebutolol enantiomers in humans. AB - The chiral beta-blocker acebutolol (AC) is marketed as a racemic mixture. Both AC and its major metabolite, diacetotol (DC), are chiral, the S-enantiomer possessing beta-blocking activity. The pharmacokinetics of AC and DC enantiomers was determined in 12 healthy subjects following oral administration of 200 mg of AC. Plasma and urine were collected over a 24-hr period and both AC and DC enantiomers were measured utilizing a stereospecific HPLC assay. Concentrations of S-AC were predominant in both plasma and urine [AUC S:R, 1.20 +/- 0.1; cumulative urinary excretion (sigma Xu) S:R, 1.17 +/- 0.05), which corresponded to a significantly greater oral clearance of R-AC (106 +/- 30 L/h) than S-AC (87 +/- 22 L/h). The Cmax of R-DC was significantly greater than for S-DC (S/R 0.7 +/ 0.1). The half-life (t1/2) of R-DC (6.4 +/- 1.6 h) was significantly shorter than that of S-DC (8.8 +/- 2.4 h). The observed AUC values for R- and S-DC were not significantly different. Renal clearance of R-DC (70 +/- 34 mL/min) was significantly greater than that of S-DC (53 +/- 29 mL/min). The data suggest that the first-pass metabolism of R-AC to R-DC is stereoselective. This metabolism, coupled with the stereoselective renal excretion of R-DC is likely a major contributor to the observed stereoselective disposition of AC and its major metabolite in humans. PMID- 1865330 TI - Easy and practical utilization of CONSAM for simulation, analysis, and optimization of complex dosing regimens. AB - Complex dosing regimens simulated in the literature using a universal dosing regimen were calculated with a general dosing program developed using the program CONSAM. The program provides a rapid method of calculating nonuniform dosing regimens for up to n = 3 compartments for any linear model. Subject data can also be curve fitted with the program to obtain individual subject estimates to allow for dosage optimization, which is important in a clinical setting. Examples are presented to show the use of the program in optimizing a theophylline regimen, as well as estimation of a new parameter, Cuneq(T), which is defined as the average non-steady-state drug concentration at time t for a drug with an irregular dosing interval. PMID- 1865331 TI - Human pharmacokinetics of betaxolol enantiomers. AB - Betaxolol is a cardioselective beta-adrenergic antagonist effective in the treatment of hypertension. The pharmacokinetic behavior of betaxolol enantiomers in healthy male subjects is reported. Betaxolol enantiomer concentrations were determined in samples collected up to 48 h after iv administration of a 10-mg dose over a 30-min period by constant-rate infusion in 12 subjects and after oral administration of 40-mg capsules to eight of the same subjects. Betaxolol extracted from whole blood was reacted with (+) or (-)-1-naphthylethyl isocyanate. The resulting diastereoisomeric derivatives were analyzed by reversed phase HPLC with fluorimetric detection. Following the iv dose, there were no differences in clearance or volume of distribution for the two enantiomers (15.6 +/- 4.4 versus 16.4 +/- 4.1 L/h and 342 +/- 62 versus 340 +/- 65 L, respectively). Likewise, after the oral dose, there were no differences in the maximum concentration, time of maximum concentration, bioavailability, or apparent absorption rate constant (41.0 +/- 8.6 versus 42.0 +/- 7.0 ng/mL, 214 +/ 59 versus 215 +/- 56 min, 0.89 +/- 0.26 versus 0.94 +/- 0.23, and 1.0 +/- 0.6 versus 1.2 +/- 0.6 h-1, respectively). Thus, the pharmacokinetic behavior of racemic betaxolol accurately reflects the behavior of betaxolol enantiomers in this subject group. PMID- 1865332 TI - Cytotoxic principles of Securinega virosa: virosecurinine and viroallosecurinine and related derivatives. AB - Virosecurinine (1) and viroallosecurinine (2) were isolated as two cytotoxic alkaloids from the leaves of Securinega virosa. A comparison of the cytotoxicity of 1 and several of its derivatives indicates that an alpha,beta- and a gamma,delta-unsaturated lactone located in a strained ring system, such as rings B, -C, and -D of 1, is structurally required for significant cytotoxicity. PMID- 1865333 TI - A quantitative structure-activity relationship approach to the minimization of albumin binding. AB - The binding of 2,6-disubstituted xanthones to human serum albumin (HSA) has been investigated using an ultrafiltration technique. A set of 26 compounds was chosen for study using a selection procedure aimed at minimizing the interparameter correlations, while ensuring that the physicochemical properties covered the maximum possible range of values. The magnitude of binding has been expressed as the compound concentration required to produce a specified bound concentration, in preference to equilibrium constants and number of albumin binding sites. Albumin binding was found to have a nonlinear dependence on the octanol-water partition coefficient (log P) and has been rationalized in terms of a simple binding model. PMID- 1865334 TI - 5-Acyl-6-aryl-4-nitro-3(2H)pyridazinones and related 4-amino compounds: synthesis and pharmacological evaluation. AB - Several 4-nitro- and 4-amino-5-acyl-6-aryl-3(2H)pyridazinones were prepared and their in vitro and ex vivo antiaggregatory properties were evaluated. 4-Nitro derivatives 3 generally showed good activity in vitro towards arachidonic acid (AA)-induced human blood platelet aggregation. The 4-amino compound 4a, which has weak in vitro activity, exhibited antiplatelet activity, particularly on adenosine dephosphate (ADP)-induced aggregation ex vivo in rabbit. Moreover, the same compound was shown to be active in platelet-activating factors (PAF)-induced rat paw hyperalgesia and to be endowed with low acute oral toxicity. The 4-amino derivatives 4a-m and the other pyridazinones 5-9 administered orally to rats were also found to be more potent antiinflammatory agents than acetyl salicylic acid (ASA). Compounds 3a and 4a, tested in vitro on lipopolysaccharide (LPS) stimulated rat peritoneal macrophages, were seen to be active in the inhibition of prostaglandin E2 (PGE2) production and interleukin-1 activity. Structure activity relationship studies in the series of antiaggregating pyridazinones 3 have shown the primary importance of the nitro and acetyl substituents at positions 4 and 5, respectively. Hydrophobic substituents at position 2 were also required for better activity. PMID- 1865335 TI - Pharmacokinetics of pyridostigmine in dogs. AB - The pharmacokinetics of the cholinesterase inhibitor pyridostigmine has been studied in six male Beagle dogs after iv infusion and after oral doses as an immediate-release syrup and as an extended-release tablet, all at a level of approximately 0.6 mg/kg. Pyridostigmine was characterized as a drug of relatively long terminal half-life (8.3 h +/- 2.1 SD), low systemic clearance (13 mL/min/kg +/- 1 SD) and high volumes of distribution (Vd lambda z, 8.7 L/kg +/- 1.9 SD and Vdss, 3.9 L/kg +/- 0.9 SD). The ratio of mean residence times in tissues and plasma was greater than 4, indicating a high affinity of peripheral tissues for the drug. This ratio was about twofold higher in three of the dogs than in the others. Pyridostigmine was slowly and incompletely bioavailable in these dogs; the systemic availability was 44.4% +/- 4.3 SD from the syrup and 33.6% +/- 9.5 SD from the tablet. Pyridostigmine disposition in these dogs was largely determined by distribution processes. PMID- 1865336 TI - High-resolution solid-state carbon-13 nuclear magnetic resonance spectra of mofebutazone, phenylbutazone, and oxyphenbutazone in relation to X-ray crystallographic data. AB - The solid-state 13C NMR spectra of mofebutazone, phenylbutazone, and oxyphenbutazone monohydrate and anhydrate are presented. The crystal structures of these pyrazolidinedione derivatives, obtained by single-crystal X-ray analysis, were previously reported, revealing distinct differences in crystal structure. In this report, the chemical shift values observed for the solid-state 13C spectra are related to the chemical environment of the various carbon atoms and compared with the crystallographic data. Results indicate that solid-state NMR spectroscopy is potentially useful in the study of drugs in the solid state. PMID- 1865337 TI - Synthesis of a fluorescent derivative of cyclosporin A for high-performance liquid chromatography analysis. AB - A direct assay method for use in studies of cyclosporin binding must be highly sensitive and selective since it must be capable of measuring the concentrations encountered in the protein-free matrix. The failure of current HPLC methods to achieve the sensitivity required for binding studies may be attributed to the use of UV detection, which relies on the relatively weak end-absorption of cyclosporin A. A method involving fluorescence derivatization was sought with the aim of increasing HPLC assay sensitivity. A method is described for producing a fluorescent derivative of cyclosporin A, a compound which has no functional groups which are easily derivatized. However, intramolecular rearrangement of cyclosporin A to form its structural isomer, isocyclosporin A, exposes a secondary amine which can be reacted with dansyl chloride to produce a fluorescent derivative. This two-step derivatization procedure was used as the basis of an HPLC fluorescence assay. Although this assay is not sufficiently sensitive to measure concentrations encountered in the protein-free matrix during plasma binding studies, the method does point to the possible development of a more sensitive assay using a derivatizing reagent other than dansyl chloride. PMID- 1865338 TI - Simultaneous determination of water-soluble vitamins by over-pressure layer chromatography and photodensitometric detection. AB - An over-pressure layer chromatographic procedure with photodensitometric detection for the simultaneous determination of water-soluble vitamins in multivitamin pharmaceutical preparations was developed and evaluated. The method uses high-performance TLC (HPTLC) plates with silica gel as the thin-layer, and an n-butanol:pyridine:water mixture (50:35:15, v/v/v) as mobile phase at a rate of 0.25 mL/min for baseline separation. The quantitation was carried out without derivatization (vitamin B1, vitamin B2, vitamin B6, folic acid, nicotinamide, vitamin C) or after spraying ninhydrin reagent (calcium pantothenate) or 4 dimethylaminocinnamaldehyde (vitamin B12, biotin). This was applied to the analysis of multivitamin solutions. Satisfactory relative standard deviations and good recovery were obtained for all the vitamins examined. It was concluded that this method is fast, accurate, specific, and suitable for routine quality control use. PMID- 1865339 TI - Plasma compatibility of injectables: comparison of intravenous U-74006F, a 21 aminosteroid antioxidant, with Dilantin brand of parenteral phenytoin. AB - The 21-aminosteroid antioxidant U-74006F (1) is being developed as an iv injectable agent for the treatment of human CNS trauma and ischemia. Because of its poor water solubility, the plasma compatibility of the parenteral formulation of 1 was evaluated using three models: (I) static solubility, (II) aggregometric, and (III) dynamic flow. The flow model was designed to mimic an iv infusion into the human antecubital vein, which was assumed to have plasma flow of 10 mL/min. Dilantin (phenytoin), the positive control, produced a precipitate in all three models from a 10% (v/v) mixture with human plasma, which approximates the in vivo ratio when the drug is infused at the recommended rate of 1 mL/min. Approximately 39% of the phenytoin dose in the flow model was retained on a downstream 3 microns filter as crystals. In comparison, the parenteral formulation of 1 produced minimal precipitate in models I and II from 40% mixtures with plasma, but higher percentages produced unstable suspensions with time-dependent precipitation. The percentage of the dose of the parenteral formulation of 1 retained on the filter in the flow model was 0.5% or less at infusion rates as high as 10 mL/min and 3% at 19 mL/min. At the 10-mL/min infusion rate, the mass of 1 retained on the filter per minute was less than 1% of the mass of phenytoin retained at the 1-mL/min infusion rate for Dilantin. The acceptable plasma compatibility of the parenteral formulation of 1 appears to be related to the solubilizing effects of plasma protein binding and pH suppression by the citric acid vehicle. PMID- 1865340 TI - Development of aqueous parenteral formulations for carbamazepine through the use of modified cyclodextrins. AB - The poor aqueous solubility of carbamazepine was dramatically increased via complexation with various chemically modified beta-cyclodextrins and gamma cyclodextrins. A preparation of carbamazepine and 2-hydroxypropyl-beta cyclodextrin was found to be stable to steam sterilization and to storage under a variety of conditions. Carbamazepine, when solubilized in this manner, was found to exert potent anticonvulsant effects in various seizure models and the formulation was tolerated in animals at high doses (100 mg/kg carbamazepine and 1200 mg/kg of the cyclodextrin excipient). The onset of anticonvulsant action was rapid and consistent with almost instantaneous in vivo complex dissociation. The low toxicity of 2-hydroxypropyl-beta-cyclodextrin, when administered via the parenteral route, and its ability to enhance the aqueous solubility of carbamazipine highly favor the use of this excipient. PMID- 1865341 TI - Oversaturated solutions of drug in hydroxypropylcyclodextrins: parenteral preparation of pancratistatin. AB - The effect of 15 cyclodextrin derivatives (polar-electroneutral, cationic, anionic, and lipophilic) and of three 2-hydroxypropyldigitonins on the solubility of pancratistatin, an anticancer drug, was evaluated. The direct solubilizations into aqueous solutions were invariably low (0.1-1.2 mg/mL compared with 50 micrograms/mL in water). Complexes of pancratistatin with hydroxypropyl-beta cyclodextrin were more stable (Kapp 153 M-1) than those with hydroxypropyl-gamma cyclodextrin (Kapp 108 M-1). Acceptable preparations were made by dissolution of pancratistatin in a large excess (50x) of hydroxypropylcyclodextrin by ammonia and then freeze drying to ammonia-free preparations. In these preparations, both the inclusion and interdispersion phenomena were operative, and the preparations dissolved rapidly forming clear solutions of pancratistatin of concentrations up to 9 mg/mL. These solutions were oversaturated and while those based on hydroxypropyl-beta-cyclodextrin precipitated within 1 h; those based on hydroxypropyl-gamma-cyclodextrin were stable for at least 4 h when kept in a plastic container (i.e., time sufficient for potential use in parenteral preparations). PMID- 1865342 TI - Phase diagram studies for microencapsulation of pharmaceuticals using cellulose acetate trimellitate. AB - Phase diagrams were prepared to indicate the region of microcapsule formation for the following system: cellulose acetate trimellitate, light mineral oil, and the solvent mixture (acetone:ethanol), using chloroform as the hardening agent. The effect of sorbitan monoleate, sorbitan monolaurate, and sorbitan trioleate on the region of the phase diagram for the formation of microcapsules was investigated. The results indicate that microcapsules are readily formed when the polymer concentration is in the 0.5-1.5% range and the solvent concentration is in the 5 10% range. Aggregation of microcapsules was minimized by using lower solvent concentration. Low concentrations of sorbitan monooleate in mineral oil (less than or equal to 1%) gave products that had smoother coats and more uniform particle size. Surfactants with low hydrophile:lipophile balance produced larger regions on the phase diagram for microencapsulation compared with a surfactant with higher hydrophile:lipophile balance. A mechanism for microencapsulation is described. Tartrazine microcapsules produced using different concentrations of surfactant were tested for dissolution characteristics in both acidic and neutral conditions. Tartrazine-containing microcapsules prepared by using 3% sorbitan monooleate had the lowest release in acidic conditions. The effect of surfactant and formulation concentration on microcapsule size was studied by analyzing the particle size distribution for both blank and tartrazine-containing microcapsules. The smallest microcapsule size was obtained when the sorbitan monooleate concentration was 3%. It appears that there is an upper limit for the surfactant concentration that could be used to achieve successful microencapsulation. PMID- 1865343 TI - Dissolution rate of griseofulvin in bile salt solutions. AB - Bile salts increase the apparent solubility of lipophilic poorly water-soluble drugs like griseofulvin. In this study, the dissolution kinetics of griseofulvin in solutions of bile salts (sodium taurocholate and sodium cholate) were investigated. A rotating disk apparatus was chosen to monitor dissolution kinetics; it well-defined hydrodynamic conditions allowed for analysis of the behavior of bile salt micelles under different conditions. Griseofulvin solubility and dissolution rate increased with increasing bile salt concentration in the dissolution medium. The enhancement of the dissolution rate was not linearly related to the solubility increase, as diffusional transport of the solubilized drug proved to be less efficient than transport of the unsolubilized ("free") drug. The dissolution process proved to be controlled by convective diffusion. An analysis of the data with the phase separation model provided results for the micellar diffusion coefficient comparable with literature data obtained with different techniques. PMID- 1865344 TI - Improved delivery of acyclovir to the skin using a dihydrotrigonelline in equilibrium with trigonelline redox carrier. PMID- 1865345 TI - Plasma concentrations of zidovudine in rats via oral administration of its ester prodrugs. PMID- 1865346 TI - Half-life revisited: implication in clinical trials and bioavailability/bioequivalence evaluation. PMID- 1865347 TI - Energetic aspects of the regulation of Ca++ sensitivity of permeabilized rabbit mesenteric artery: possible involvement of a second Ca++ regulatory system in smooth muscle contraction. AB - The effects of phosphagen concentrations and adenosine-5'-O-(2 thiodiphosphate)(ADP beta S), a nonhydrolyzable ADP analog, on the pCa++ tension relationships were investigated, using alpha-toxin permeabilized rabbit mesenteric artery. The removal of creatine phosphate (CP) greatly affected the Ca++ sensitivity and induced a leftward shift of the pCa++ tension curve. Addition of ADP beta S (10-300 microM) also caused a leftward shift of the pCa++ tension curve. Ca++ solutions (0.3-10 microM) containing 0.1 mM ATP did not induce contraction. However, the addition of CP in the presence of 0.1 mM ATP dose-dependently increased force development which reached a maximum around 3 mM CP. A 10 microM Ca++ solution containing 0.1 mM ATP and 1 mM CP was much more effective in inducing contraction than a 10 microM Ca++ solution containing 1.1 mM ATP alone, although the total concentration of phosphagen (ATP + CP) was the same. Application of 0.1 mM ATP solution containing various concentrations of Ca++ after the maximal Ca+(+)-induced contraction relaxed the tissue, with the higher Ca++ concentrations inducing the faster relaxation. The same pattern of the relaxation was seen when the tissue was pretreated with adenosine-5'-O-(3 thiotriphosphate) beforehand. The contractile state observed in the Ca+(+)-free solution containing 0.1 mM ATP and 0.1 mM CP was completely relaxed by 1 mM vanadate, consistent with the idea that the sustained contraction was due to accumulation of the actomyosin-ADP complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865348 TI - Correlation of the amnestic effects of nicotinic antagonists with inhibition of regional brain acetylcholine synthesis in rats. AB - Acetylcholine (ACh) is considered to play a primary role in normal mnemonic functioning. Although most research has centered on the central muscarinic cholinergic system, of recent interest in normal and pathologic cognitive processing is the role of the nicotinic cholinergic system. The purpose of this research was to further characterize the role of the nicotinic system in learning and memory processing in a classical passive avoidance task by rats. The centrally acting nicotinic antagonist mecamylamine produced a dose-dependent impairment of performance in the passive avoidance task, however, the peripherally acting nicotinic antagonist hexamethonium was ineffective in this test. To elucidate the potential neurochemical mechanisms underlying mecamylamine's amnestic effect, we examined the ability of the drug to alter specific dynamic components of rat brain cholinergic systems in five brain regions. Mecamylamine produced a dose-dependent inhibition of the synthesis of [3H]ACh from pulse-injected [3H]choline in all regions examined, but was without effect on endogenous, steady-state levels of ACh. As with the behavioral study, administration of hexamethonium was without effect on [3H]ACh synthesis. Calculation of the turnover rates of ACh allowed a correlation between the inhibition of the behavioral task and the inhibition of central cholinergic function. The high degree of correlation obtained (as well as earlier studies in nonhuman primates) underlined the possibility that presynaptically located nicotinic receptors on brain cholinergic neurons are tonically active and mediate a positive feedback mechanism for controlling cholinergic neuronal activity. These receptors may be the neurochemical substrate which underlie the behavioral changes after administration of nicotinic agonists and antagonists. PMID- 1865349 TI - The antifibrillatory actions of UK-68,798, a class III antiarrhythmic agent. AB - The electrophysiologic and antifibrillatory properties of UK-68,798 were studied in vivo in a conscious canine model of sudden coronary death. Electrophysiologic testing was performed on conscious male mongrel dogs (14.5-21.5 kg) 3 to 5 days after surgical induction of an anterior myocardial infarction by occlusion (2 h) reperfusion of the left anterior descending coronary artery. Compared to saline treated control animals, UK-68,798 at a dose of 0.9 mg/kg i.v. did not (P = .083) suppress the induction of ventricular tachycardia by programmed electrical stimulation. Six of 12 UK-68,798-treated dogs remained inducible, whereas 10 of 12 vehicle-treated dogs responded to electrical induction of arrhythmia. When compared to predrug inducibility, UK-68,798 significantly (P = .007) reduced the incidence of programmed electrical stimulation-induced ventricular tachycardia. In five of the six dogs inducible after UK-68,798 administration, the cycle length of the induced ventricular tachycardia was prolonged (P = .007) compared to the predrug cycle length. Heart rate, PR interval and QRS duration were not affected by UK-68,798 administration. The rate-corrected QT interval was prolonged (P less than .05) by UK-68,798. The ventricular effective refractory period was increased by UK-68,798 (158 +/- 7 msec, predrug vs. 185 +/- 7 msec, postdrug). Subsequent to programmed electrical stimulation, a 150 microA anodal current was applied to the luminal surface of the left circumflex coronary artery to induce transient episodes of posterolateral ischemia in response to electrolytic injury of the vessel wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865350 TI - L-dihydroxyphenylalanine methyl ester is a potent competitive antagonist of the L dihydroxyphenylalanine-induced facilitation of the evoked release of endogenous norepinephrine from rat hypothalamic slices. AB - Using high performance liquid chromatography with electrochemical detection, we attempted to find among L-dopa-related analogs a competitive antagonist against L dopa-induced facilitation of impulse (2 Hz)-evoked endogenous norepinephrine (NE) release from rat hypothalamic slices. At the first screening in the presence of cocaine and 3-hydroxybenzylhydrazine (NSD-1015), a L-aromatic amino acid decarboxylase inhibitor, L-dopa (1-100 nM) concentration-dependently facilitated NE release. L-dopa (1 microM) reduced NE release. D-dopa, L-phenylalanine, 3-O methyl-dopa, 3,4-dihydroxyphenylacetic acid or L-dopa-phosphate at 1 to 1000 nM, and carbidopa (1-10 nM), did not mimic L-dopa. L-dopa methyl ester (0.3-10 nM) concentration-dependently decreased NE release, suggesting that it is antagonistic, whereas L-threo-3,4-dihydroxyphenylserine (0.001-1 nM) concentration-dependently mimicked L-dopa. At the second screening in the additional presence of S-sulpiride, L-dopa (1-1000 nM) concentration-dependently facilitated NE release. Maximum effect was seen at 0.3 to 1 microM. Pretreatment with carbidopa (0.1-10 nM) or L-dopa phosphate (0.01-0.1 nM) was somewhat antagonistic. L-Dopa methyl ester (3-30 nM) in a concentration-dependent manner shifted the concentration-facilitation curve for L-dopa to the right: Schild plots gave a straight line with a slope of 1.00 and pA2 was 8.9, whereas l propranolol (1-100 nM) concentration-dependently reduced maximal effect of L-dopa without rightward shift of the curve. L-Dopa methyl ester and some large neutral amino acids inhibited uptake of [3H]-L-dopa into slices in the presence of NSD 1015.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865351 TI - Cocaine pharmacokinetics in the pregnant guinea pig. AB - The pharmacokinetics of cocaine (COC) were studied during late gestation in guinea pigs. Clearance (Cl) was not dose-dependent and the average +/- S.D. was 59 +/- 16 ml/min/kg over the i.v. dose range of 2 to 12 mg/kg. Volume of distribution at steady state (Vdss), mean resident time (MRT) and elimination half-life (T1/2) were dose-dependent over this dose range with changes occurring between the 2 and the 4 mg/kg dose of COC. Vdss was 2.1 and 3.9 l/kg. MRT time was 42 and 57 min, and elimination T1/2 was 34 and 49 min at the 2 and 4 mg/kg dose, respectively. Cl and Vdss values after 2 to 20 mg/kg of COC s.c. were similar to those after i.v. administration, whereas MRT was significantly greater as a result of delayed absorption. Absorption of COC s.c. was nearly complete (84%) and had a T1/2 of 51 min. Benzoylecgonine (BE) and benzoylnorecgonine (NOR) were major and persistent metabolites of COC. Norcocaine was present after COC doses of 4 mg/kg or higher but could only be detected during the first 2 hr. PMID- 1865352 TI - Adenosine A1 and A2 receptors mediate presynaptic inhibition and postsynaptic excitation in guinea pig submucosal neurons. AB - Intracellular recordings were made from guinea pig submucosal neurons in vitro. Adenosine, 2-[p-(carboxyethyl)phenylethylamino]-5'-N- ethylcarboxamidoadenosine (CGS21680), 2-chloroadenosine (CADO), 5'-N-ethylcarboxamidoadenosine (NECA), R(-) N6-(2-phenylisopropyl)adenosine (R-PIA), N6-cyclohexyladenosine (CHA) and 1-deaza 2-chloro-N6-cyclopentyladenosine (DCCPA) were applied by adding them to the superfusion solution. Adenosine (30 nM to 30 microM) depolarized S-type neurons neurons and this was mimicked by analogs with potency order: CGS21680 = NECA greater than R-PIA greater than CADO greater than adenosine greater than CHA much greater than DCCPA. 8-Cyclopentyltheophylline (CPT) blocked the depolarizing action of CADO or R-PIA; this antagonism was surmountable and the dissociation equilibrium constant (KD) estimated by the Schild method was 295 nM. Synaptic potentials were evoked by focal stimulation of nerve strands running between submucosal ganglia. The nicotinic excitatory postsynaptic potential was reduced by adenosine and analogs with potency order CHA = R-PIA greater than DCCPA = NECA = CADO greater than adenosine much greater than CGS21680; CPT competitively antagonized this effect of CADO or CHA with a KD of 13 nM. The noradrenergic inhibitory postsynaptic potential was also reduced; the potency order was R-PIA greater than CHA = CADO = NECA = DCCPA greater than adenosine much greater than CGS21680; the KD of CPT as an antagonist was 7 nM. It is concluded that adenosine directly depolarizes submucosal neurons by acting at an A2 receptor, and that it inhibits the release of acetylcholine (from intramural nerves) and noradrenaline (from sympathetic nerves) by acting at a presynaptic A1 receptor. PMID- 1865353 TI - Age-related differences in the effects of some muscarinic agents on acetylcholine release from rat neostriatal slices. AB - The purpose of this study was to investigate whether the muscarinic modulation of neostriatal acetylcholine release changes with senescence. Neostriatal slices from Fischer 344 rats aged 3, 10 and 28 months were prepared and incubated in Krebs-Ringer bicarbonate buffer oxygenated with 95% O2/5% CO2. Acetylcholine release from slices of each age group was monitored in the presence or absence of muscarinic agents, and the release in the presence of the drug was compared to the release from slices of age-matched controls in the absence of drug. The muscarinic agonist, oxotremorine, and two muscarinic antagonists, atropine and pirenzepine, were tested for their effects on acetylcholine release. Pirenzepine is selective in its interaction with the M1 muscarinic receptor subtype; atropine and oxotremorine are nonselective in their actions. Of the three drugs tested, pirenzepine displayed a significant age-related difference in its effects on acetylcholine release. Whereas the effects of pirenzepine (50 microM) on acetylcholine release modulation in slices from the 3-month rats were negligible, the M1-selective antagonist increased the release of acetylcholine from slices of 10- and 28-month rats by another 42 and 192% (P less than .05), respectively. Atropine (1 microM) was also tested, and an increase in acetylcholine release by another 64, 104 and 218% (all P less than .05) was observed in slices from the 3 , 10- and 28-month rats, respectively. In the presence of oxotremorine (50 microM), acetylcholine release decreased in slices from the 3-month rats by 35% (P less than .1), but changed by only 7 and 15% in the 10- and 28-month slices, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865354 TI - Analgesic and hyperthermic effects of intravenously administered morphine in the rat are related to its serum levels. AB - The analgesic response, colonic temperature changes and the pharmacokinetic parameters of i.v. administered morphine sulfate (2.5, 5.0 and 10.0 mg/kg) through indwelling cannulas in the jugular vein were determined in male Sprague Dawley rats. The analgesic and hyperthermic responses were determined before and at 30-min intervals for a period of 360 min after the morphine injection and were expressed as area under the time-response curve. Blood samples were collected periodically for a period of 24 h. Serum was separated and was used for the estimation of morphine by the highly sensitive radioimmunoassay. The pharmacokinetic parameters, half life, the terminal elimination rate constant, the mean residence time, the apparent volume of distribution at steady state and the total clearance were determined by using noncompartmental analysis. The area under the serum concentration-time curve from time zero to infinity was related to the dose of morphine. The other parameters were the same for all the doses of morphine, except the serum levels of morphine extrapolated to zero time which increase gradually with the dose. Dose-dependent analgesic and hyperthermic responses were related to the area under the serum concentration-time curve. It is concluded that the dose-dependent pharmacological effects of morphine were related to the area under the serum concentration-time curve from time zero to infinity for serum levels of morphine but not to the other pharmacokinetic parameters. PMID- 1865355 TI - Endothelin and calcium signaling in NG108-15 neuroblastoma x glioma cells. AB - Endothelin (ET)-mediated Ca++ signaling in NG108-15 neuroblastoma x glioma cells was studied by measuring free intracellular Ca++ (Ca++i) levels with the fluorescent Ca++ indicator, fura-2. ET-1 produced biphasic increases in Ca++i consisting of a transient peak elevation followed by a sustained plateau phase. Both peak and plateau Ca++i responses to 5 nM ET-1 were reduced by depletion of extracellular Ca++. Peak responses were also attenuated by inhibitors of inositol phosphate metabolism, whereas plateau responses were affected by dihydropyridine Ca++ channel agonists and antagonists and by differentiation. These results suggest that peak Ca++i responses to ET-1 involve mobilization of Ca++ from inositol phosphate-sensitive intracellular stores and influx of extracellular Ca++ through nonclassical Ca++ channels, whereas plateau responses are mediated by Ca++ influx through dihydropyridine-sensitive, voltage-gated channels. PMID- 1865356 TI - Mechanisms for the uptake of cationic drugs by the liver: a study with tributylmethylammonium (TBuMA). AB - The mechanisms of hepatic organic cation transport were examined in isolated rat hepatocytes, using the model compound [methyl-3H]tributylmethylammonium (TBuMA). [3H]TBuMA is shown to be taken up into rat hepatocytes by two carrier-mediated systems in addition to a nonsaturable process. The transport mechanisms for TBuMA share common features with both the type I and type II carrier systems reported for exogenous organic cations such as procainamide ethobromide and vecuronium, respectively. Only slight effects were seen in the presence of relatively high concentrations of endogenous organic cations such as thiamine, choline and N1 methyl nicotinamide. The total uptake of [3H]TBuMA was neither influenced by an electronegative membrane potential and variations in external and internal pH, nor by the absence of Na+, K+ or Cl- in the incubation medium. The presence of the inorganic anion I- stimulated the uptake of [3H]TBuMA. An improved presentation or binding to the carrier may be involved because symport with the anion could not be demonstrated. Lowering of the temperature produced a significant reduction in the uptake velocity of [3H] TBuMA, whereas metabolic inhibitors such as valinomycin and carbonylcyanide-m-chlorphenylhydrazone reduced the uptake rate by 80 and 90%, respectively, which was correlated with the extent of ATP depletion. It is concluded that the monovalent cationic drug TBuMA can be considered as a mixed type I/type II compound that exhibits an electroneutral and anion-sensitive uptake mechanism, depending on metabolic energy. The uptake mechanism is dissimilar from Na(+)-dependent and H(+)-dependent transport systems that have been described for endogenous cations, such as thiamine, choline and N1 methylnicotinamide. PMID- 1865357 TI - Naltrexone modulation of nicotinic acetylcholine receptor activity. AB - The narcotic antagonist naltrexone (NTX) has both depressant and excitatory effects on nicotinic acetylcholine receptor activity, and the present study was primarily concerned with mechanisms involved in the latter modulatory action. Single channel data were recorded in cell-attached mode from cultured embryonic chick skeletal muscle myotubes at 10 degrees C under control conditions (0.15 or 0.3 microM acetylcholine, ACh) or in the presence of NTX (0.15 microM ACh plus 0.1-5 microM NTX). Distributions of open and closed times indicated that there were at least two open and four closed channel states in all cases, and evidence for at least two gateways between the open and closed classes was provided by autocorrelation data. In the absence of NTX the proportion of long (greater than 2 msec) openings increased with increasing ACh concentration, suggesting that the channel in both the mono- and biliganded forms of the receptor could open. Three possible six-state models of channel kinetics which were compatible with these findings could not be distinguished on the basis of conventional Markov modeling of open and closed times; however when account was taken of burst distributions, one model was clearly superior. Estimated transition rates in this model showed that enhanced receptor activity in the presence of NTX was due mainly to increased cooperativity of ACh binding. The results suggest that in the chick nicotinic ACh receptor, low micromolar concentrations of NTX may cause enhancement and blockade of activity by binding to a site which is allosterically coupled to several activation and gating processes. PMID- 1865358 TI - Interaction between methotrexate, "rescue" agents and cell proliferation as modulators of homocysteine export from cells in culture. AB - Clinical studies on cancer and psoriasis patients have shown that plasma and urinary homocysteine (Hcy) responds to methotrexate (MTX) therapy, indicating that Hcy in extracellular fluids may be an indicator of the antifolate effect. However, the clinical data indicate that the burden of proliferating cells, cytotoxicity and the folate status are also determinants of extracellular Hcy. To evaluate this further, we investigated the modulation of cellular Hcy egress by MTX, rescue agents, cell proliferation and cytotoxicity. Nontransformed and chemically transformed fibroblasts and murine lymphoma cells, which are characterized by different growth behavior and MTX response, were used. The Hcy export rate was correlated positively with the proliferation rate in all cell types. 5-Formyltetrahydrofolate or 5-methyltetrahydrofolate added to fibroblasts not exposed to MTX reduced the Hcy export rate, whereas the export from the lymphoma cells was not affected. All cells types exposed to MTX were rescued by thymidine + hypoxanthine, and this allowed the assessment of Hcy export during MTX exposure without interference from cytotoxicity. In the fibroblasts, MTX with thymidine + hypoxanthine rescue induced a marked increase in Hcy export, and the dose-response paralleled the cytotoxicity curves obtained for MTX without rescue. Nontoxic concentrations of MTX without rescue enhanced the Hcy export. When MTX concentration was increased further, Hcy export was stimulated initially, and then declined rapidly as cell death ensued. MTX did not enhance the Hcy export from the lymphoma cells and, in the absence of rescue, the Hcy export from these cells declined in proportion to inhibition of cell growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865359 TI - Caffeine and theophylline as adenosine receptor antagonists in humans. AB - Substantial in vitro and animal data suggest that methylxanthines, such as caffeine and theophylline, act as adenosine receptor antagonists. To test this hypothesis in humans, we first determined if theophylline would antagonize the effects of adenosine. Intravenous administration of adenosine, 80 micrograms/kg/min, increased heart rate 28 +/- 6 bpm, systolic blood pressure 19 +/- 5 mm Hg and minute ventilation 6.1 +/- 2.2 liters/min. All these changes were significantly attenuated during theophylline administration (17 +/- 3 bpm and 1 +/- 2 mm Hg and 1.6 +/- 0.6 liters/min, respectively, P less than .05), at a dose (10 mg/kg over 1 hr, followed by 1.8 micrograms/kg/min i.v.) that produced plasma theophylline levels of 17 +/- 2 micrograms/ml (94 microM). We then determined if chronic caffeine consumption resulted in upregulation of platelet adenosine receptors in eight normal volunteers. After 7 days of caffeine abstinence, the adenosine analog 5'-N-ethylcarboxamidoadenosine produced a dose-dependent inhibition of thrombin-induced aggregation (EC50 = 69 nM). Subjects then were given caffeine, 250 mg p.o. 3 times a day for 7 days. Actual caffeine withdrawal, that is, virtual disappearance of caffeine in plasma, was apparent 60 hr after the last dose of caffeine. Caffeine withdrawal produced a significant shift to the left of 5'-N-ethylcarboxamidoadenosine inhibition of aggregation (EC50 = 49 nM, P less than .01), implying sensitization and/or upregulation of adenosine receptors as seen after chronic exposure to an antagonist. These results suggest that methylxanthines act as adenosine receptor antagonists in humans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865360 TI - Tetanus toxin and neuronal membranes: the relationship between binding and toxicity. AB - Tetanus toxin labeled by the Bolton-Hunter technique possesses high specific activity and retains substantial biological activity. This material can be used to characterize tetanus toxin binding to receptors in brain membrane preparations. In experiments aimed at measuring the absorption of labeled toxin, the displacement of labeled toxin by unlabeled toxin and the on-rate and off-rate constants, the data revealed two binding sites. The high affinity site had a Kd of 0.033 to 0.070 nM and a Bmax of 0.26 to 0.4 pmol/mg of protein; the low affinity site had a Kd of 0.89 to 6.9 nM and a Bmax of 1.55 to 3.0 pmol/mg of protein. The binding of tetanus toxin to brain membranes was enhanced greatly by low pH and ionic strength. Similarly to tetanus toxin, botulinum neurotoxin could be labeled by the Bolton-Hunter technique, and its binding to brain membranes was also enhanced by low pH and ionic strength. In studies with a neutralizing monoclonal antibody against tetanus toxin, the antigen-antibody interaction was not significantly altered by media with low ionic strength and pH. On the other hand, the ability of the antibody to block toxin binding to brain membranes was reduced substantially in nonphysiologic media. In a bioassay aimed at determining the effect of pH and tonicity on tissue association by toxin, low pH and ionic strength did not enhance toxicity. The biological activity of tetanus toxin was unaffected and that of botulinum neurotoxin was greatly diminished. The present findings confirm the widely reported observation that low pH and ionic strength promote tissue association by tetanus toxin, but they challenge the premise that this binding is relevant to the normal process of cell poisoning. PMID- 1865361 TI - Lipolytic activity of progesterone and synthetic progestins on rat parametrial adipocytes in vitro. AB - Despite the known lipogenic properties of progesterone (P) in vivo, one study had previously reported a direct in vitro lipolytic activity of P on isolated adipocytes from rat parametrial adipose tissue (Sutter-Dub et al., 1981). The aim of the present study was to further investigate this finding. Parametrial, but not retroperitoneal adipocytes, isolated from 6-week-old female rats, showed an increase in glycerol release under P stimulation. Estrone, estradiol, estriol and testosterone were inactive. At 12 weeks of age, parametrial adipocytes were bigger and failed to respond to P. P-stimulated glycerol release was concentration-related between 10(-7) M and 10(-5) M. Compared to norepinephrine, P activity displayed less potency (EC50 around 5 X 10(-7) M vs. 10(-6) M, and 4 fold vs. 2-fold maximal stimulation, respectively). Compared to P, synthetic progestins used in therapeutics (medroxyprogesterone acetate, norethindrone acetate, megestrol acetate and nomegestrol acetate) were more active at 10(-7) M but did not induce a greater response at 10(-5) M. Some 17 alpha-hydroxy and 17 alpha-acetoxy derivatives of P or 19-norprogesterone were also tested at 10(-5) M. General agreement was found between experimental lipolytic activities and known progestative agonist properties, with the exception of 19-norprogesterone, which showed a reduced lipolytic activity compared to P, in contrast with its usually higher progestative potency. The direct in vitro lipolytic activity of P was characterized as specific of age and of the parametrial adipose tissue, concentration-related, and common to synthetic progestins. PMID- 1865362 TI - Purified choleragenoid does not induce migrating action potential complex activity in rabbit ileum in vivo. AB - The migrating action potential complex (MAPC), a single ring contraction that propels luminal contents abroad, is elicited by Vibrio cholerae and its enterotoxin, choleragen (A1A2B5), in rabbit ileal loops in vivo. Choleragenoid (B5; the binding subunit) was shown previously to induce MAPCs without activating the adenylate cyclase system and without stimulating fluid output. We restudied purified B5 (extracted by high-performance liquid chromatography) to assess its effects on the myoelectric activity of rabbit ileum: can MAPC activity can be induced without associated fluid production? Four different B5 preparations and two controls, V. cholerae and sterile saline, were used. MAPC activity and ileal fluid output were significantly increased in animals inoculated with A1A2B5 (V. cholerae-El Tor) compared with all other preparations and controls. Importantly, MAPC activity and fluid output in all B5 groups did not differ from those in saline controls, demonstrating that purified B5 does not induce MAPC activity in rabbit ilium in vivo. The previous study showing B5-induced MAPCs may have resulted from A1A2B5 contamination. These results suggest A1A2B5-induced adenylate cyclase activation; myoelectric activity may be interrelated with holotoxin binding that causes a neural response. PMID- 1865363 TI - Response of rat thoracic aortic rings to thromboxane mimetic U-46,619: roles of endothelium-derived relaxing factor and thromboxane A2 release. AB - Studies were designed to test the role of the endothelium and endogenous release of thromboxane (Tx) A2 in the contractile response of rat thoracic aortic rings to the TxA2/prostaglandin (PG) H2 mimetic, U-46,619. U-46,619 caused a dose dependent contraction of rings with endothelium (mean ED50 = 6.54 +/- 3.02 x 10( 9) M; n = 13) which was abolished by the TxA2/PGH2 receptor antagonist, SQ 29,548. Removal of endothelium greatly potentiated (P less than .05) the contractile response to U-46,619 (ED50 = 4.78 +/- 2.14 x 10(-10) M; n = 14). On addition to the organ bath, oxyhemoglobin (10(-6) M), an inhibitor of endothelium derived relaxing factor, increased vascular smooth muscle contraction in response to U-46,619 and abolished the difference in response between rings with endothelium (ED50 = 6.63 +/- 0.38 x 10(-11) M) and those without (ED50 = 5.13 +/- 0.18 x 10(-11) M). Vascular contraction with U-46,619 (10(-7] was associated with release of immunoreactive TxB2 and 6-keto PGF1 alpha as well as increased conversion of [14C]arachidonate to [14C]TxB2 and 6-keto-[14C]PGF1 alpha. To test the role of endogenous TxA2 in response to U-46,619, the TxA2 synthetase inhibitor UK-38,485 (10(-6) M) was added directly to the organ bath; this diminished (P less than .05) the contractile responses to U-46,619 of rings with and without endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865364 TI - Effect of accumulation of NKY-722, a water-soluble vasoselective Ca++ antagonist, on KCl-induced contraction in isolated canine mesenteric arteries. AB - The relationship between the accumulation of NKY-722 and its vasoinhibitory effect on KCl-induced contraction was examined in canine mesenteric arteries. NKY 722 showed a high level of accumulation in canine mesenteric arteries and reached near maximal levels at 60 min. The tissue/medium ratio measured at 60 min was independent of the bath concentration of NKY-722 (10(-9), 10(-8) and 10(-7) M). NKY-722 (10(-9) and 10(-7) M) attenuated the KCl (30 mM)-induced contraction of canine mesenteric arteries, and this effect was dependent on the pretreatment time (5-60 min). The vasoinhibitory effect of NKY-722 (during incubation) on KCl induced contraction correlated with its accumulation in the vascular preparations. Preparations were incubated with NKY-722 (5 x 10(-9) M) for 60 min and repetitively washed out, showing that the accumulation of NKY-722 decreased slowly over 300 min. When the preparations were incubated with NKY-722 (5 x 10( 9) M) for 60 min, the vasoinhibitory effect on KCl-induced contraction remained for over 300 min after repetitive washouts. The vasoinhibitory effect of NKY-722 (during washout) on KCl-induced contraction also correlated with its accumulation in the vascular preparations. The present experiments indicate that NKY-722 accumulates in canine mesenteric arteries at high levels and should be washed out slowly, and suggest that NKY-722 accumulation in vessel walls may contribute to the long duration of its antihypertensive effect. PMID- 1865365 TI - U-78517F: a potent inhibitor of lipid peroxidation with activity in experimental brain injury and ischemia. AB - U-78517F (2-[4-[2,6-di-(1-pyrrolidinyl)-4-pyridinyl)-1-piperazinyl] methyl]-3,4 dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol, dihydrochloride), which combines the antioxidant ring portion of alpha-tocopherol together with the amine of the previously described 21-aminosteroids (e.g., U-74006F), is a novel inhibitor of iron-catalyzed lipid peroxidation. U-78517F was found to have a 50% inhibitory concentration (IC50) of 0.6 microM against 200 microM ferrous chloride initiated lipid peroxidation in rat brain homogenates, compared to 8 microM for U 74006F, 28 microM for alpha-tocopherol and 43 microM for the ring portion of alpha-tocopherol (i.e., trolox). Both stereoisomers of the racemic U-78517F proved to be equally active antioxidants. Against lipid peroxidation initiated by xanthine/xanthine oxidase, U-78517F was even more potent, with an IC50 of 0.01 microM. U-78517F was also observed to protect cultured mouse spinal neurons against iron-induced damage, with an IC50 of approximately 0.5 microM. When administered to male CF-1 mice i.v. at 5 min after a severe concussive head injury. U-78517F produced a dose-related improvement in the 1-hr neurological recovery. The minimum effective i.v. dose was 1.0 micrograms/kg. Measurement of U 78517 concentrations in the brains of mice after administration of a 10-mg/kg i.v. dose revealed effective antioxidant levels for as long as 2 hr. Evidence of an in vivo antioxidant action was provided by the attenuation of iron-induced blood-brain barrier disruption (i.e., Evans' blue extravasation) in rats pretreated with U-78517F.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865366 TI - Presystemic and systemic chiral inversion of R-(-)-fenoprofen in the rat. AB - Fenoprofen (FN), a member of the 2-arylpropionic acid (2-APA) class of nonsteroidal anti-inflammatory drugs is administered clinically as a racemate. In humans, FN has been shown to rapidly undergo substantial in vivo unidirectional chiral inversion with the inactive R-isomer converted to its active antipode. As with any p.o. administered drug, before reaching the systemic circulation. FN may undergo first-pass metabolism, the major organs involved being the gastrointestinal tract and/or the liver. The site(s) of inversion for the 2-APAs have been a subject of debate, with presystemic intestinal metabolism in humans and hepatic systemic metabolism in rats receiving the most attention. The inversion of R-FN was studied in the male Sprague-Dawley rat 1) in vivo after p.o. and i.v. administration of racemic-FN and R-FN, 2) after perfusion of R-FN into isolated liver (single-pass and recirculation) and 3) after a 2-hr incubation with everted intestinal tissue (duodenum, jejunum, ileum and colon) and noneverted stomach pouch. The enantiomers and their acyl-glucuronides were quantitated using a previously developed stereospecific assay. With the isolated liver, R-FN was shown to invert in both the single-pass and recirculation systems, with a first-pass extraction ratio of 0.3. A significant but variable inversion in all intestinal segments was observed. Substantial inversion by the duodenum was observed (serosal S:R ratio, 1.2) with maximal inversion by the jejunum (serosal S:R ratio, 2.2), whereas inversion of R-FN was absent in the stomach. Considerable glucuronidation was observed in all tissues studied including first-pass glucuronidation of both enantiomers after single-pass perfusion through the isolated liver and stereoselective glucuronidation in intestinal tissue segments. The results indicate that, in the male Sprague-Dawley rat, R-FN undergoes presystemic inversion by both the gastrointestinal tract and liver. These results, however, must be viewed with caution as they may not necessarily be extrapolated to other 2-APAs or species. PMID- 1865367 TI - Studies of concanavalin A in nonobese diabetic mice. II. Lymphocyte tracking and phenotype responses. AB - We studied the tracking of 51chromium-labeled (resting) and Con A-induced (activated) tritiated thymidine-labeled syngeneic lymphocytes to adrenal, blood, brain, heart, liver, lymph nodes, pancreas, spleen, testis/ovary, thymus and thyroid in prediabetic, nonobese diabetic (NOD) mice and in age- and sex-matched C57BL/6 mice. 51Chromium-labeled cells showed no significant difference between strains in tracking to any tissue except lymph nodes (decreased in NOD vs. C57, P less than .05). Con A incubation resulted in no difference between strains in lymphocyte tracking to lymph nodes, but NOD mice had increased pancreatic tracking with Con A-incubated cells compared to C57 mice (P less than .05). Female NOD mice had reduced thymic tracking (P = .001) compared to C57 controls. Positive selection experiments showed the Con A-responsive cell to be a T cell. Both Lyt2+ (CD8+) and L3T4+ (CD4+) enriched T cell populations showed a labeling response to Con A. After 48 h of Con A incubation, the L3T4+/Lyt2+ ratio increased in splenocytes from NOD mice (P less than .05), whereas it decreased in C57 controls (P less than .01). Over the course of 6 days in culture, NOD splenocytes exposed to Con A characteristically exhibited a delayed expansion of the Lyt2+ population. We conclude that Con A incubation of NOD splenocytes results in T cells that, when reinfused, avoid the thymus and track preferentially to the pancreas. Con A immunomodulation as potential treatment for autoimmune disease warrants further study in this murine model. PMID- 1865368 TI - Propafenone disposition and pharmacodynamics in normal and norepinephrine-induced cardiomyopathic rabbit hearts. AB - The myocardial disposition and pharmacodynamics of propafenone were studied in 10 normal and 10 norepinephrine-induced cardiomyopathic rabbit hearts. The left ventricular propafenone concentrations measured after perfusion of propafenone (0.3 microM) for 150 min were similar in the normal group (18 +/- 8 micrograms/g) compared to the cardiomyopathy group (20 +/- 5 micrograms/g, P = NS). However, the concentration of propafenone in cardiomyopathic left ventricular papillary muscle, which was always extensively involved in the inflammatory process, was significantly lower (11 +/- 2 micrograms/g) compared to normal papillary muscle (19 +/- 4 micrograms/g, P less than .05). During propafenone perfusion a significantly greater increment in ventricular conduction time was observed in the cardiomyopathy group (17 +/- 6 msec) compared to the normal group (12 +/- 3 msec, P less than .05). The propafenone myocardial concentration-effect relationships describing changes in QRS duration were shifted to the left in the cardiomyopathy group. Furthermore, the slopes of these linear concentration effect relationships were greater in the cardiomyopathy group (1.80 +/- 0.60 msec/micrograms/g) compared to the normal group (1.07 +/- 0.25 msec/micrograms/g, P less than .01). The ventricular effective refractory period was shorter at base line in the cardiomyopathy hearts (156 +/- 21 msec) compared to the normal group (176 +/- 23 msec, P less than .08). However, propafenone effects on changes in the ventricular effective refractory period were similar in the two groups. Thus, the myocardial accumulation of propafenone is reduced in areas of extensive necrosis observed in norepinephrine-induced cardiomyopathy. As well, cardiomyopathic tissue is more responsive to propafenone effects on ventricular conduction time. PMID- 1865369 TI - Inhibitory influence of the mesocortical dopaminergic neurons on their target cells: electrophysiological and pharmacological characterization. AB - Both dopaminergic (DA) and noradrenergic (NA) systems exert an inhibitory influence on the activity of prefrontal cortical neurons (PFC). As NA-containing fibers run close to the dorsal ventral tegmental area (VTA), electrical stimulation of the VTA might coactivate both DA and NA systems. In the present study extracellular recordings and microiontophoresis were used in anesthetized rats to analyze first whether the inhibitory cortical responses to VTA stimulation and DA application were mediated by DA or adrenergic receptors. Inhibitory responses elicited by DA application or VTA stimulation were observed in PFC output neurons identified by antidromic activation from subcortical structures. Both types of inhibitory effects were reversed by the DA antagonist sulpiride, but not by the adrenergic antagonists prazosin (alpha-1), yohimbine (alpha-2) or propranolol (beta). NA and the beta agonist isoproterenol inhibited the activity of PFC cells and these effects were antagonized by propranolol, but neither by prazosin and yohimbine nor by the DA antagonist sulpiride. Thus, the inhibitory influence of the mesocortical DA system in the PFC involves DA, but not NA, recognition sites. The DA receptor subtype mediating the inhibitory effects of VTA stimulation and DA application in the PFC was analyzed further. VTA- and DA-evoked inhibitory responses were antagonized by the D2 selective antagonists (-)-sulpiride, LUR 2366 and RIV 2093, but not by the D1 selective antagonist SCH23390. In addition, the DA-induced inhibitory response was mimicked by the selective D2 agonist LY 171555 but not by the selective D1 agonist SKF 38393. Surprisingly, haloperidol, which is also a potent D2 antagonist, failed to consistently block DA- and VTA-induced inhibitory effects. The present results indicate that the inhibition of PFC cells by mesocortical DA neurons is mediated via a subtype of DA receptors which is particularly sensitive to benzamides. PMID- 1865370 TI - Toxicity to isolated hepatocytes caused by the intracellular calcium indicator, Quin 2. AB - To determine whether incubation for several hours with intracellular Ca++ indicators caused toxicity to freshly isolated hepatocytes from rats, cells were incubated under 95% O2-5% CO2 in medium containing 2 mM Ca++ and the acetoxymethyl (AM) esters of Quin 2, Indo 1, Fluo 3, 5,5'-Dimethyl BAPTA, 4,4' Difluoro BAPTA or Fura 2 for up to 5 hr. Quin 2-AM and Indo 1-AM (2.5 microM) induced lipid peroxidation in the cells after 1 or 3 hr of treatment, respectively. Additional experiments with Quin 2-AM (25 microM) revealed that it also caused lactate dehydrogenase leakage, cell blebbing and vitamin E loss in cells, but did not affect reduced glutathione or intracellular Ca++ content. The ability of Quin 2-AM to cause toxicity was dependent on the amount of Quin 2 which was present in the cell. Ca++ appeared to be involved in the mechanism of Quin 2-AM toxicity, for modulation of the extracellular Ca++ concentration partially inhibited lipid peroxidation, vitamin E loss, cell blebbing and lactate dehydrogenase leakage. PMID- 1865371 TI - Involvement of calcium and iron in Quin 2 toxicity to isolated hepatocytes. AB - When treated with the cytosolic Ca++ indicator Quin 2-acetoxymethyl ester (Quin 2 AM), isolated hepatocytes exhibited signs of toxicity, such as extensive lipid peroxidation and vitamin E loss and release of lactate dehydrogenase. Lipid peroxidation induced by this agent was blocked completely by cotreatment of the cells with ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, EDTA, ruthenium red, carbonyl cyanide m-chlorophenylhydrazone, desferal and trifluoperazine, and was partially inhibited by quinacrine and indomethacin. With the exception of carbonyl cyanide m-chlorophenylhydrazone and quinacrine, these agents also inhibited lactate dehydrogenase leakage. Although the results with ruthenium red suggested that Quin 2-AM may cause toxicity by altering handling of Ca++ by mitochondria, mitochondrial membrane potential was not altered in cells treated with Quin 2-AM until after toxicity occurred. Evidence of a direct, potentiative effect of Quin 2 on iron-induced lipid peroxidation was gained from experiments with liposomes. Treatment of cells with Quin 2-AM did not enhance nitro blue tetrazolium reduction, suggesting that Quin 2 did not stimulate O2- production by the cells. Direct chelation of Ca++ did not appear to be involved in the mechanism of Quin 2 toxicity, for an analog of Quin 2 that is virtually nonhydrolyzable, which greatly limits the binding of Ca++, also caused lipid peroxidation and cell death. These results suggest that Quin 2 causes toxicity by chelating iron or by activating some cellular process(es) that is dependent on the presence of iron or Ca++. PMID- 1865372 TI - Proceedings of the Physiological Society. Charing Cross and Westminster meeting, 10-11 January 1991. Abstracts. PMID- 1865373 TI - Proceedings of the Physiological Society. University College London meeting, 25 26 March 1991. Abstracts. PMID- 1865374 TI - Proceedings of the Physiological Society. Sheffield joint meeting with the British Society for Clinical Neurophysiology, 19-20 April 1991. Abstracts. PMID- 1865375 TI - Proceedings of the Physiological Society. Royal Free meeting, 15-16 February 1991. Abstracts. PMID- 1865376 TI - Patients who develop postanesthesia shaking show no difference in postoperative temperature from those who do not develop shaking. AB - While the cause of postanesthesia shaking (PS) remains unknown, nurses traditionally believe that the etiology of PS is hypothermia. Two theoretical constructs have been proposed to describe the development of PS. The first is based on classic thermoregulation theory. The second is based on spinal reflex hyperactivity. The purpose of this comparison study was to determine if significant differences in postoperative temperature, as well as change in preoperative to postoperative temperature, exists between patients who develop and who do not develop PS. The study also examined the difference in postoperative temperature between women and men. Postoperative axillary temperature was measured on admission to the PACU. The nonprobability convenience sample consisted of patients between the ages of 18 and 89 years who were extubated and breathing spontaneously following general anesthesia. PS developed in 120 of 533 patients. By t-test analysis, there was no statistical significant difference between groups in postoperative mean temperature (P greater than .10) or in preoperative to postoperative mean temperature change (P greater than .40). The group that developed PS had a narrower and higher range of postoperative temperature and a smaller preoperative to postoperative temperature change than those who did not develop PS. In both groups, 52% of the patients were hypothermic (less than 35 degrees C[less than 95 degrees F]) on PACU admission. Women had lower postoperative mean temperature than men (P less than .05). Findings indicate that temperature on PACU admission is not a variable of difference between groups of patients who develop or who do not develop PS. As postoperative temperature decreases, the incidence of PS does not increase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865377 TI - Postoperative joint replacement pain: description and opioid requirement. AB - The present research was designed to describe the character, severity, and factors associated with postoperative pain following total hip replacement (THR) and total knee replacement (TKR) surgery, and to identify amounts of opioid required to relieve that pain. It was the investigators' intention to investigate the impact of age on severity of pain and amount of opioid required after surgery. Complete data were obtained on 29 white subjects, 16 of whom were men. Subjects' ages ranged from 27 to 88 years (mean, 66). The mean age for the men was 61 years and the mean age for the women was 72 years. Twelve subjects underwent THR and 17 underwent TKR. Eight patients received general anesthesia and 21 received spinal anesthesia. Pain was described using the McGill Pain Questionnaire-Short Form and quantified using a visual analogue scale. Amount of opioid required to relieve pain over 24 hours was recorded using a patient controlled analgesia pump. Data analysis indicated that most patients do not report their pain as being controlled when discharged from the PACU, and that patients who receive spinal anesthesia require more postoperative opioid to control pain than patients who receive general anesthesia. In general, patients who undergo TKR experience more pain than patients who undergo THR. Pain was described as moderate to severe aching. As age increases, patients self administer less postoperative opioid, but they do not report less postoperative pain. PMID- 1865378 TI - A new approach to postanesthesia care unit documentation. AB - Documentation demonstrates that nursing standards of care have been met. To be an effective tool, a record must be complete and concise. A request to develop PACU care plans became the impetus to revise the PACU record. Perioperative information and physical assessments are data required to formulate individualized plans. Development and implementation of a comprehensive record was a positive outcome of a lengthy but interesting and worthwhile project. PMID- 1865379 TI - A standards of care plan in the postanesthesia care unit. AB - Every patient is entitled to consistent, high-quality, individualized care. The PACU staff and former director of staff education at Southwestern Vermont Medical Center developed a documentation tool to achieve this end. The primary focus of the tool is on standards of care with an emphasis on outcome standards. Every patient received and cared for in the PACU is evaluated in terms of these outcome standards. If for any reason an outcome standard is not achieved, appropriate action is taken. The four-page bifold tool incorporates the nursing process. Potential nursing diagnostic problems are described and assessment and intervention data are integrated accordingly. The plan is further individualized vis a vis nursing progress notes. The tool has been in use for well over 1 year, and quality assurance studies demonstrate that outcome standards achieved and not achieved are consistently documented. The PACU staff believe this tool has enhanced professional practice and improved use of the nursing process and standards of care. PMID- 1865380 TI - A perioperative case study of frontal lobe meningioma. PMID- 1865381 TI - Meningioma: nursing care considerations. AB - In spite of over 100 years of surgical experience with the brain tumor, meningioma, it continues in many cases to be a challenge. Although benign by nature, meningiomas may be difficult to resect and a small percentage may recur. Surgical intervention is the treatment of choice for complete abolition of the tumor. Following surgery, astute nursing care is required to promote physiological stability while monitoring for life-threatening complications. PMID- 1865382 TI - Organizational issues in nursing case management. AB - The nursing case manager has a critical role in achieving the high level of interdepartmental communication, mutual adjustment, and coordination necessary for efficient and effective patient care. This article addresses organizational factors that influence the nursing case manager's role in the interconnectedness of the departments. PMID- 1865383 TI - Prevention of accidental injection of drugs in epidural tubing. AB - Numerous drugs have been injected into the epidural space unintentionally and different methods of prevention have been reported. This article describes the use of a needle cap as an available cost-effective alternative to prevent this mishap. PMID- 1865384 TI - Rationing health care resources: who will set limits? AB - Hospitals faced with additional reductions in Medicare and Medicaid reimbursements are discontinuing unprofitable services and programs. Nurses and physicians are finding that the patient's care plan is often dictated by economic considerations rather than what they believe to be beneficial. This article provides an overview of the problems and considerations involved in the rationing of health care resources. PMID- 1865385 TI - Transcending specialization. PMID- 1865386 TI - Morphological correlates of pyramidal cell adaptation rate in the electrosensory lateral line lobe of weakly electric fish. AB - 1. Extracellular HRP injections into the nucleus praeeminentialis dorsalis (NPd) of Apteronotus leptorhynchus retrogradely labeled a population of electrosensory lateral line lobe (ELL) efferent cells, deep basilar pyramidal cells, that differ morphologically from the previously described basilar and nonbasilar pyramidal cells. These neurons are found deep in the ELL cellular layers; they have small cell bodies and very short sparsely branching apical dendritic trees. The previously described basilar and nonbasilar pyramidal cells are larger, have extensive apical dendrites and are found more superficially. 2. Axon terminals of the deep basilar pyramidal cells were recorded from in the NPd and labeled with lucifer yellow. These NPd afferents have high, regular spontaneous firing rates, and respond tonically to changes in electric organ discharge amplitude. 3. Deep basilar pyramidal cell bodies were recorded from and labeled in the ELL, and these showed the same physiological responses as did the NPd afferent fibers. 4. In addition, basilar pyramidal cells were found which had spontaneous activity patterns and adaptation characteristics intermediate to those typical of the superficial basilar pyramidal cells and the deep basilar pyramidal cells. The size of the pyramidal cells' apical dendritic trees and the placement of their somata within the dorsoventral extent of the ELL cellular layers are highly correlated with the neurons' physiological properties. PMID- 1865387 TI - Effects of temperature, steroids and castration on daily torpor in the Djungarian hamster (Phodopus sungorus). AB - 1. In Phodopus sungorus the frequency and characteristics of daily torpor were not affected by a decrease in temperature. The seasonal cycle of daily torpor is essentially under photoperiodic control. 2. Testicular regression is a necessary condition for daily torpor occurrence. Testosterone and 5 alpha dihydrotestosterone administration totally inhibited daily torpor in hamsters which were exposed to short days. The temporal inhibition of torpor by steroids had no effect on the seasonal time measuring mechanism governing daily torpor. 3. Castration influenced certain aspects of the daily torpor display. Castrated hamsters showed a delay in terminating torpor season lending further support to the hypothesis that recrudescence of the testis plays a role in terminating the daily torpor season. Castration, when performed before or on the day of transfer to short photoperiod led to an increase in the frequency of torpor bouts and reduce SP exposure duration which is necessary for the daily torpor season beginning. PMID- 1865388 TI - Tissue factor in chronic villitis of unestablished etiology. AB - We have previously reported the presence in normal human placentae of coagulation, macrophages and helper T lymphocytes in inflammatory foci known as villitis of unestablished etiology. In order to investigate the link between coagulation and immunity, we have studied fetal stem vessel endothelium for tissue factor, which is made available by cytokines and activates coagulation via the extrinsic pathway. We found that fetal stem vessel endothelial cells of normal chorionic villi did not react with antibody to tissue factor. Normal placentae contain small numbers of villitis areas and endothelium in these areas was reactive with antibody to tissue factor. Endothelial tissue factor reactivity was more prominent in placentae from secondary recurrent spontaneous aborters and these placentae have greatly increased numbers of villitis areas. The tissue factor availability on fetal stem vessel endothelium may result from immunologically mediated cytokine release. The net effect of these reactions is the presence of lymphocytes, macrophages, coagulation, necrosis and vasculitis in villitis. PMID- 1865389 TI - Immunoregulatory effects of ovine trophoblastin protein (oTP): all five isoforms suppress PHA-induced lymphocyte proliferation. AB - The immunosuppressive properties of ovine trophoblastin protein (oTP) isoforms purified to homogeneity by DEAE HPLC have been studied within and across species barriers by in vitro assays. It has been demonstrated that not only the classical oTP 1, but in fact all 5 isoforms, are immunosuppressive in a PHA-induced proliferation assay, whilst being ineffective on IL-2 dependent CTL-L2 cell replication. The significance of these findings is discussed. PMID- 1865390 TI - Identification and characterization of human acrosomal antigen defined by a monoclonal antibody with blocking effect on in vitro fertilization. AB - A monoclonal anti-human sperm antibody (Mab 1A1) has been produced by fusion of myeloma cells with splenocytes from a BALB/c mouse immunized with in vitro capacitated human spermatozoa. Immunofluorescence studies with Mab 1A1 show that it recognizes an antigen(s) (Ag 1A1) which is located in the acrosome of human spermatozoa. As shown by Western blotting experiments, 1A1 antigen represents a family of proteins with Mr ranging from 20 kDa to 34 kDa. Immunofluorescence observations on epitope exposure and location suggest that during in vitro capacitation of human spermatozoa, Mab 1A1 epitope-bearing molecules are concentrated in regularly arranged granules in the acrosome. After long-term incubation the epitope is exposed on the apical acrosome surface exhibiting a spot-like arrangement. The 1A1 epitope is widely distributed among mammalian species: boar, ram, mouse and rat acrosome is intensively stained by Mab 1A1. The antibody inhibits in vitro fertilization mainly by blocking sperm attachment to and penetration through the zona pellucida when included in the medium for the in vitro fertilization of mouse, porcine and human oocytes. PMID- 1865391 TI - Evaluation of human sperm-zona pellucida tight binding by presence of monoclonal antibodies to sperm antigens. AB - Characterized WHO monoclonal antibodies (MAbs) to human sperm antigens were evaluated as to whether they inhibited sperm-zona pellucida tight binding as assessed by the hemizona assay (HZA). Of the 26 MAbs tested, only one inhibited zona binding. The whole sperm-specific MAb inhibited zona binding by 70%. The MAb also caused strong agglutination. Two procedures, Sephadex column chromatography and papain digestion, were used to determine whether agglutination or steric hindrance was a factor in the capability of MAb to inhibit zona binding. However, inhibition remained comparable to previous results. The MAb did not prevent capacitation, nor calcium influx and the resulting increase in hyperactivated motility and acrosome reaction. Since its inhibitory influence is not due to agglutination factors, steric hindrance or prevention of normal pre-fertilization maturation, the MAb may be blocking a portion of the zona binding receptor and may be useful in elucidating sperm antigens important to sperm-egg interaction. The approach used in this study allows definition of sperm surface antigens involved in zona pellucida binding. PMID- 1865392 TI - Inhibition of human sperm-zona pellucida tight binding in the presence of antisperm antibody positive polyclonal patient sera. AB - Patient sera previously characterized as containing high levels of IgG and IgA antisperm antibodies that bound to the sperm surface, most specifically the head region, were evaluated for their effect on sperm-zona pellucida tight binding as assessed by the hemizona assay (HZA). Of the ten patient sera tested, 7 reduced zona binding by approximately half. Two of the most strongly inhibitory (greater than 70% inhibition) were examined for their effect on the prefertilization maturation of sperm. The patient sera did not affect sperm motion characteristics, or development of hyperactivated motility. However, in the presence of these sera some impedance was noted in calcium uptake after stimulation with human follicular fluid and in the acrosome reaction after calcium ionophore induction. Whether these two sera specifically affect sperm zona pellucida binding or non-specifically affect the normal progression of capacitation remains to be eludicated. PMID- 1865393 TI - Analysis of litter size and weight in mice differing in Ped gene phenotype and the Q region of the H-2 complex. AB - A gene has been described, Ped (Preimplantation embryo development), that influences the rate of cleavage of preimplantation mouse embryos. Previous studies of linkage of Ped gene phenotype (fast or slow embryo development) and H 2 haplotype (H-2b or H-2k) in backcross embryos from the C57BL/10Sn and B10.BR congenic strains have shown that the Ped gene is located in the H-2 complex, the major histocompatibility complex (MHC) of the mouse. The present study was undertaken to localize the Ped gene to a particular subregion of the H-2 complex. Analysis of the B6.K1 and B6.K2 congenic strains, which differ at only the Q subregion of the MHC, was undertaken to test whether the Ped gene is located in the Q subregion of the MHC. Qa-2 antigen expression was used as a marker for the Q subregion and fast or slow development was used to assess Ped gene phenotype in backcross embryos generated from the mating of (B6.K1 x B6.K2)F1 and B6.K1 mice. The results showed linkage of Ped gene phenotype and Qa-2 antigen expression, which strongly supports the idea that the Ped gene is located in the Q subregion of the MHC. In a further set of experiments, litter size and weight were investigated in the B6.K1 and B6.K2 mice. Pure line and reciprocal crosses were made using sires and dams of both the B6.K1 and B6.K2 genotypes. Traits measured on pups included birth weight, weaning weight and weight per day of age from birth to weaning. Litter traits measured were number born and weaned and survivability. Sex effects existed for weaning weight and weight gain per day of age. Males gained more and were heavier than female pups (P less than 0.05). Pups whose sire or dam were B6.K2 were significantly (P less than 0.05) heavier at birth than those pups whose sire or dam were B6.K1, and B6.K2 homozygous pups were significantly (P less than 0.001) heavier than all others. Litters whose dams were B6.K2 had significantly more pups at birth (P less than 0.05) than those litters whose dams were B6.K1. Results suggest that pups that are heterozygous or homozygous B6.K2 are more apt to be heavier at birth and be in larger litters suggesting that genes in the Q region of the H-2 complex are advantageous to reproductive performance. PMID- 1865394 TI - Detection of class I MHC mRNA in subpopulations of first trimester cytotrophoblast cells by in situ hybridization. AB - Class I MHC mRNA has been identified in both villous and extravillous cytotrophoblast cells in first trimester placentas by in situ hybridization. In this report, we expand those observations to additional morphologically and anatomically distinct subpopulations of trophoblast cells in early placentas using the same experimental approach. In the transition zone of first trimester placental villi, where cytotrophoblast cells are proliferating to form new villi or to migrate into adjacent tissue, both cytotrophoblast cells beneath the uninterrupted syncytium and the proliferating cytotrophoblast cells contained class I mRNA whereas a layer of cytotrophoblast cells proximal to the villus core did not contain class I mRNA. In the placental bed, migrating cytotrophoblast cells contained high levels of class I mRNA as determined by the intensity of staining. In contrast, multinucleated giant trophoblast cells contained little specific message. Alterations in levels of class I mRNA seem therefore to be associated with trophoblast proliferation, migration and differentiation. PMID- 1865395 TI - Umbilical cord prolapse: a contemporary look. PMID- 1865396 TI - Transabdominal chorionic villus sampling for rapid karyotyping in advanced gestation. AB - Late pregnancy fetal karyotyping is not employed often because a clinical decision about labor and delivery may be required before the results would be available. However, percutaneous umbilical blood sampling (PUBS) has been used recently to obtain fast karyotypes. We have extended our chorionic villus sampling (CVS) procedure to the second and third trimesters and compared the results obtained with late CVS and PUBS. CVS karyotypes were obtained faster and may be technically easier to perform. PMID- 1865397 TI - Efficacy of danazol in the control of hormonal migraine. AB - Of 131 women with hormonally related migraines unresponsive to standard medication, 67 (51.1%) noted profound relief after a 12-month, phased study using danazol for migraine prevention. The first three phases consisted of two-month cycles: dietary control and acetazolamide, the addition of danazol and danazol discontinuation. Eighty-three women (63.36%) reported control of their hormonal migraines while using danazol. In phase IV, 81 women whose headaches were controlled by danazol restarted danazol for an additional six months. Sixty-seven (82.7%) reported continued success with this medication. Danazol proved highly successful in the control of women's cyclic migraine. Its effectiveness remained consistent throughout the treatment course. In the prophylactic treatment of women's hormonal migraine, 400 mg of danazol administered daily for 25 days each month can prove effective when standard medical therapy fails. Furthermore, the response to danazol supported the concept that hormonal migraine should be treated as a distinct clinical entity. PMID- 1865398 TI - Use of the drop volume of amniotic fluid in predicting fetal lung maturity. Clinical experience. AB - Respiratory distress syndrome (RDS), resulting from inadequate amounts of alveolar surfactant, is a leading cause of neonatal mortality. This study analyzed the drop volume for predicting the risk of neonatal RDS by evaluating the surface tension of amniotic fluid. The drop-volume method quantifies the surface tension of amniotic fluid using the fact that the volume of a falling drop of liquid is proportional to the quantity of surface-active substances (surfactant) in the solution. Distilled water is used as a reference solution. The test is simple to perform and requires only two minutes and 2 mL of amniotic fluid. Amniotic fluid was obtained by amniocentesis from 120 pregnancies, ranging from 24 to 42 weeks of gestation, within four days of delivery. Specimens contaminated with meconium or hemolyzed blood or from patients with clinical chorioamnionitis were not used. The lecithin:sphingomyelin ratio and phosphatidylglycerol tests were also determined for 54 of the study cases. A mature drop-volume test result was associated with a healthy infant with no RDS 95% of the time (negative predictive value). Fifty-two percent of the healthy infants in the study were predicted by an arbitrary unit of time (S) value of less than or equal to 85.0 (specificity). Thirteen of the 16 infants who developed RDS (81%) were predicted by an S value of greater than or equal to 85.1 (sensitivity). Of those infants with an S value of greater than or equal to 85.1, 21% developed RDS (positive predictive value). PMID- 1865399 TI - Smoking and buccally administered nicotine. Acute effect on uterine and umbilical artery Doppler flow velocity waveforms. AB - The effects of maternal smoking and buccal nicotine exposure on uterine and umbilical artery blood flow velocity waveforms were studied in 47 healthy women during late pregnancy. Systolic:diastolic ratios of recorded waveforms were calculated before and after each woman smoked one cigarette containing 1.2 mg of nicotine. The same protocol was followed at a subsequent clinic visit, when each woman chewed a piece of nicotine polacrilex containing 2 mg of nicotine. No significant changes could be induced in either nonsmokers or prior smokers, nor were any significant changes measured in the uterine vessels of any patient subgroup. A significant decrease (P less than .01) in umbilical artery diastolic blood flow velocities was measured after smoking in all habitual smokers after chewing nicotine polacrilex and in those who smoked greater than 10 cigarettes per day (P less than .05). All the measured changes returned to baseline levels by 10 minutes after cessation of exposure. Similar changes in the umbilical artery flow velocity waveforms after exposure to a cigarette and nicotine polacrilex implicated nicotine as a probable cause. Failure to observe significant changes except in habitually smoking women suggests a receptor mediated response. The finding of altered umbilical artery flow velocity waveforms in the absence of demonstrable changes in the uterine vessels indicates a direct toxic effect of maternal nicotine exposure on the fetal cardiovascular system. PMID- 1865400 TI - Brucellosis in pregnancy. AB - Brucellosis in pregnancy is a rare entity. It has been associated with an increased risk of spontaneous abortion in animals and possibly humans. Among six patients with brucellosis in pregnancy, one requested termination of the pregnancy in the first trimester, one had a spontaneous abortion at 12 weeks that could not be directly related to brucellosis, and four continued their pregnancies with no significant increase in maternal or neonatal morbidity or mortality. PMID- 1865401 TI - Amniotic cavity accumulation of magnesium with prolonged magnesium sulfate tocolysis. AB - In seven women, continuous intravenous tocolysis with magnesium sulfate for 4-28 days resulted in high amniotic fluid magnesium levels (10.54 mg% +/- 1.83 SD). In all cases the amniotic fluid magnesium level greatly exceeded the maternal serum level in a sample collected simultaneously. Additionally, when amniorrhexis and delivery occurred within one hour of each other, the fetal magnesium levels uniformly exceeded the maternal levels in paired maternal and cord blood samples. PMID- 1865402 TI - Gastric carcinoma presenting as an exacerbation of ulcers during pregnancy. A case report. AB - Gastric cancer is unusual during pregnancy. Also, because of the physiologic changes that occur with pregnancy, it is rare to see a worsening of peptic ulcers during pregnancy. A patient with an exacerbation of peptic ulcers presented with gastric carcinoma during pregnancy. PMID- 1865403 TI - Necrotizing fasciitis in irradiated tissue from diabetic women. A report of two cases. AB - Two diabetic women with pelvic malignancies developed necrotizing fasciitis within the irradiation fields. Despite aggressive surgical and medical therapy, both died when their health became too unstable for them to tolerate further surgery to resect the residual infection. We attribute their poor outcome to several factors. First, postradiation tissue changes obscured the early clinical findings necessary for a prompt diagnosis and made the identification of adequate surgical margins difficult. Second, diabetic patients have increased susceptibility to this infection. Third, the cumulative effects of radiation, diabetes mellitus and other factors that are common in patients with gynecologic malignancy (advanced age, vascular disease, obesity) favor the development, progression and persistence of necrotizing fasciitis. Radiographic studies were helpful in defining the extent of the infection in one patient. PMID- 1865404 TI - Cervical pregnancy. A report of two cases. AB - Cervical pregnancy is a rarely occurring form of ectopic pregnancy. Given its rarity, the identification of risk factors is based on anecdotal case reports and occasional summarizing reviews. We managed two additional cases with a new, conservative approach. The trend is away from radical therapy and toward conservation of reproductive function. PMID- 1865406 TI - Evaluating combination drug therapy in rheumatoid arthritis. PMID- 1865407 TI - Standard self-report questionnaires in routine clinical and research practice--an opportunity for patients and rheumatologists. PMID- 1865405 TI - Wegener's granulomatosis complicated by pregnancy. A case report. AB - A 23-year-old woman who presented in the 17th week of her third intrauterine pregnancy was diagnosed as having active Wegener's granulomatosis. Therapy, consisting of corticosteroids, cyclophosphamide and hemodialysis, was instituted and maintained until delivery. Although Wegener's granulomatosis complicated by pregnancy has been reported previously, this is the first reported patient to be treated successfully with the above agents during the second and third trimesters without apparent harm to her or her infant. PMID- 1865408 TI - Vasculitis and the gut: unwitting partners or strange bedfellows. PMID- 1865409 TI - Relation between patients' own health assessment and clinical and laboratory findings in rheumatoid arthritis. AB - Health status encompasses not only physical aspects, but also psychological and social aspects. A multidimensional health status questionnaire was used in 69 Dutch patients with rheumatoid arthritis to assess their physical, psychological and social well being. The same day clinical and laboratory data were recorded. The health status questionnaire provided additional information to clinical and laboratory findings. The various clinical and laboratory measures of disease activity reflect aspects other than the self-reported measure of physical well being. As such they are not interchangeable. Furthermore clinical and laboratory measures of physical well being appeared to be unrelated with psychological and social measures. In contrast, the patients' self-report of physical well being was related only with depressive mood and to some extent with anxiety. PMID- 1865410 TI - Marital status in rheumatoid arthritis and other rheumatic disorders: a study of 7,293 patients. AB - Divorce has been considered to be increased in rheumatoid arthritis (RA), perhaps as a result of the stress of serious chronic illness. We studied marital status in 7,293 consecutive rheumatic disease patients attending an outpatient rheumatic disease clinic. Divorce was associated with age, sex, population size, and ethnic origin, but when these factors were controlled for, divorce was not more common in the 1,267 patients with RA. Age and sex adjusted divorce percentages for RA and non-RA patients were 6.9 and 6.8 compared with a U.S. percentage of 7.6. Patients with RA, however, were almost 5 times less likely to be remarried after divorce than patients with osteoarthritis. PMID- 1865411 TI - Analysis of methotrexate treatment effect in a longitudinal observational study: utility of cluster analysis. AB - We studied 235 patients with rheumatoid arthritis (RA) beginning therapy with methotrexate utilizing a k-means clustering algorithm. Four groups were identified: mild RA (Group 3), very severe RA (Group 4), and 2 groups intermediate in severity (Groups 1 and 2). Group 2, the largest of the clusters (n = 89), appeared to have greater tolerability of RA as measured by severity and psychological variables, and took the drug almost twice as long as other groups, although improvement was not greater nor side effects fewer. All groups improved over a mean of 1.9 years, and the degree of improvement was not related to the initial severity classification. Improvement occurred almost equally in all clusters, and the relative ranking of the groups was maintained at study closure. PMID- 1865412 TI - Presence of immunoreactive endothelin in synovial fluid: analysis of 22 cases. AB - The endothelins are a family of recently defined active peptides with a wide range of activities, including the activation of the synthesis of prostaglandins. The concentration of endothelin in inflammatory and noninflammatory synovial fluids (SF) was measured by a sensitive radioimmunoassay. Endothelin-like immunoreactivity was detectable in all SF samples and the mean concentration of endothelin was 2.6 +/- 0.3 pg/ml, more than twice that in normal human plasma. The mean level of endothelin in SF in rheumatoid arthritis was 2.5 +/- 0.4 pg/ml (n = 11), and was not statistically different from either osteoarthritis, 3.0 +/- 0.5 pg/ml (n = 7), or acute inflammatory arthritis, 2.0 +/- 0.4 pg/ml (n = 4). Our data do not support the hypothesis that endothelin plays an important role in the pathogenesis of inflammatory arthritis. PMID- 1865413 TI - Glucocorticoid receptors in systemic lupus erythematosus. AB - Glucocorticosteroids remain the major treatment modality for systemic lupus erythematosus (SLE), but their mechanism of action is unclear. Over the past decade it has become clear that glucocorticosteroid receptors play a significant role in the mechanism of glucocorticosteroid action. We studied glucocorticosteroid receptor density and affinity on peripheral blood mononuclear cells by the glucocorticosteroid binding assay in 33 patients with SLE who had taken no glucocorticosteroid for the previous 6 months and in 32 healthy controls. Patients' disease activity was measured by the SLE Disease Activity Index (SLEDAI). Glucocorticosteroid receptors on leukocytes of patients with SLE were significantly higher than in healthy controls (4419 +/- 306 vs 3369 +/- 196, p less than 0.005). The binding affinity was not different between patients and controls. There was no correlation between glucocorticosteroid receptor number and SLE disease activity. PMID- 1865414 TI - Esophageal involvement in mixed connective tissue disease. AB - A study of esophageal symptoms and function was performed in 21 patients with mixed connective tissue disease (MCTD). Esophageal involvement was found in 18 cases (85%), in 14 (66%) with typical symptoms, in 15 (71%) with manometric abnormalities and in 11 (57%) with both. The manometric pattern was characterized by reduction of amplitude and coordination of peristaltic waves throughout the esophageal body and reduction of lower esophageal sphincter (LES) competency. In comparison, 38 patients with systemic sclerosis showed a similar but more severe pattern, particularly at the level of the distal esophagus and LES. Thus, although similar, the esophageal involvement in MCTD was not exactly the same as that of systemic sclerosis. Furthermore, in MCTD a correlation between manometric abnormalities and cutaneous involvement was lacking, and this suggests that esophageal disorders are not always linked with clinically evident scleroderma like features of this disease. Since the diagnosis of MCTD is made in the presence of the clinical picture of more than one connective tissue disease, the detection of esophageal involvement by a sensitive technique such as esophageal manometry in a patient with suspected MCTD may be a useful diagnostic aid. PMID- 1865415 TI - Effect of bucillamine (SA96) on type II collagen induced arthritis in rats. AB - The effects of bucillamine, a new antirheumatic drug, on type II collagen induced arthritis in rats was examined. Bucillamine inhibited hindpaw swelling in a dose dependent manner. The histopathological study indicated that bucillamine inhibited the proliferation of synovial lining cells. The anti-type II collagen antibody level was also decreased by the treatment with bucillamine. D penicillamine, on the other hand, showed no beneficial effects on arthritis except for inhibiting new bone formation. Our findings suggest that bucillamine has beneficial effects on type II collagen induced arthritis in rats and that its mechanism of action is different from those of D-penicillamine. PMID- 1865416 TI - Primary ankylosing spondylitis, psoriatic and enteropathic spondyloarthropathy: a controlled analysis. AB - Within our ankylosing spondylitis (AS) population (n = 1331), 85% (n = 1128) had primary AS (1 degree AS), 9% (n = 121) had psoriatic AS (PsAS) and 6% (n = 82) enteropathic AS (IBDAS). In an attempt to explore further the relationship between 1 degree AS and the secondary spondyloarthritides, we evaluated 121 consecutive patients with PsAS and 82 with IBDAS, as well as 202 controls with primary disease. The patients were matched for sex and age at review PsAS:48.1 (SD 11.3) years vs 1 degree AS:48.4 (SD 11.5), and IBDAS:46.0 (SD 12.7) vs 1 degree AS:45.9 (SD 12.7). The sex distribution for IBDAS (M:F, 1:1), was significantly less (p less than 0.001) than that for PsAS (M:F, 3.5:1) or 1 degree AS (M:F, 2.4:1). Overall, compared to 1 degree AS the PsAS and IBDAS tended to have greater disease severity as defined by e.g., (1) those taking non steroidal antiinflammatory drugs, 86 vs 72% (p less than 0.01) and 71 vs 60% (p less than 0.05), respectively; (2) decreased spinal mobility (scale 0-8) 5.0 (SD 2.0) vs 4.4 (SD 2.3); p = 0.029 and 4.9 (SD 2.0) vs 3.9 (SD 2.4); p = 0.024, respectively; and (3) PsAS resulted in a higher AIMS pain score; 4.9 (SD 2.5) vs 4.0 (SD 2.4): p = 0.042. By contrast, peripheral joint involvement, number of total hip replacements and capacity for employment were similar in all 3 groups. In conclusion (1) among the AS population the prevalence of 1 degree AS, PsAS and IBDAS is 90, 6 and 4%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865417 TI - Chondrocyte nonresponsiveness of arthritic articular cartilage caused by short term immobilization. AB - We studied the effect of short term immobilization on chondrocyte synthetic function. Arthritis from intraarticular injection of either glucose oxidase or interleukin 1 (IL-1) led to suppression of proteoglycan synthesis. Extension casting of arthritic knees prevented inhibition of proteoglycan synthesis, whereas later casting restored synthesis to normal. During chronic antigen induced arthritis casting protected chondrocyte synthesis for a period of 5 days. The chondrocyte nonresponsiveness was not from altered penetration of suppressing substances. Radiolabelled biologically active IL-1 showed no difference in retention or localization in articular cartilage of either mobile or immobile knees. Flexion casting did not induce unresponsiveness of chondrocytes and suppression of synthesis was similar to that in mobile arthritic knees, indicating the importance of loading. The nonresponsiveness occurred only during immobilization and rapidly disappeared after removal of the cast, provided that suppressing agents were still present. Thus, during short term immobilization chondrocytes are protected from inhibition of proteoglycan synthesis by suppressing agents. This protection may benefit repair of the depleted cartilage matrix with waning inflammation. PMID- 1865419 TI - The fibromyalgia impact questionnaire: development and validation. AB - An instrument has been developed to assess the current health status of women with the fibromyalgia syndrome. The Fibromyalgia Impact Questionnaire (FIQ) is a brief 10-item, self-administered instrument that measures physical functioning, work status, depression, anxiety, sleep, pain, stiffness, fatigue, and well being. We describe its development and validation. This initial assessment indicates that the FIQ has sufficient evidence of reliability and validity to warrant further testing in both research and clinical situations. PMID- 1865418 TI - Rheumatic manifestations in myelodysplastic syndromes. AB - The myelodysplastic syndromes are characterized by ineffective hematopoiesis with possible transformation to acute nonlymphocytic leukemia. We describe a patient with refractory anemia with excess blasts with unusual rheumatic manifestations of vasculitis, migratory synovitis, arthralgias, and myalgias. A retrospective review over a 6-month period of 162 patients with myelodysplastic syndromes found 16 patients (10%) with several rheumatic manifestations. We divided these manifestations into 4 different categories: cutaneous vasculitis, "lupus-like syndrome," neuropathy, and patients with both a rheumatic disease and a myelodysplastic syndrome. There were 7 with cutaneous vasculitis including leukocytoclastic vasculitis and other individual cases of urticarial vasculitis and panniculitis; 3 with lupus-like manifestations with histological evidence of an inflammatory process; 3 with neuropathic manifestations including peripheral neuropathy, mononeuritis with foot drop, and chronic inflammatory demyelinating polyneuropathy; and 3 patients in which their myelodysplastic syndrome was diagnosed after their rheumatic disease was known, including rheumatoid arthritis. Sjogren's syndrome and mixed connective tissue disease. The class with refractory anemia with excess blasts had 9 patients with rheumatic manifestations but also had the largest number of patients in the study (46/162 or 29%). Three of the 16 patients died, all from the refractory anemia with excess blasts class, reflecting the known mortality in this group of patients. We believe there is a significant association between myelodysplastic syndromes and rheumatic manifestations. PMID- 1865420 TI - Chronic myeloid leukemia in a woman with Still's disease treated with 198Au synoviorthesis. AB - A 32-year-old woman presented with chronic myeloid leukemia 20 years after 2 198Au synoviortheses to her knees for severe juvenile rheumatoid arthritis. She progressed to blast phase of her disease and died from complications of therapy. The literature on rheumatoid arthritis, its therapy, radioisotopes and leukemia is reviewed. PMID- 1865421 TI - Complete reversal of rheumatoid nodulosis. AB - A woman first seen in 1978 had a history of seropositive rheumatoid arthritis (RA) of 12 years' duration with attacks of palindromic rheumatism for 3 years. She was treated with D-penicillamine, pyridoxine and hydroxychloroquine and serial measurements of her grip strength and proximal interphalangeal joint circumference were taken. By 1987 all her nodules had resorbed completely. Hydroxychloroquine effects probably helped her improvement. Although spontaneous resorption of a rheumatoid nodule is not a rare event, to the best of our knowledge, this is the first instance of complete resolution of all nodules in a patient with RA with the nodulosis variant. PMID- 1865422 TI - Bone remodelling after growth factor and cyclosporine A therapy for aplastic anemia. AB - We describe a patient with viral induced aplastic anemia who developed severe bone pain after treatment with multiple courses of antithymocyte globulin, cyclosporine A, recombinant human granulocyte macrophage colony stimulating factor and deferoxamine. Radiographs and bone biopsy revealed extensive new trabecular bone formation in long bone diaphyses and adjacent periosteal reaction. The effects of hematopoietic growth factors, cyclosporine A and deferoxamine on bone metabolism are reviewed. PMID- 1865423 TI - Subcutaneous cholesterol crystals mimicking calcinosis cutis in systemic sclerosis. AB - A patient is described with systemic sclerosis (SSc) and subcutaneous cholesterol crystals mimicking calcinosis cutis. Though not detectable radiographically, basic calcium phosphate crystals were identified by alizarin red staining of aspirate from one digit. The value of crystal identification by microscopy in cases of SSc with presumed calcinosis cutis, but without radiographic evidence of subcutaneous calcific deposits, is emphasized. PMID- 1865424 TI - Bowel perforation and interstitial cystitis in childhood systemic lupus erythematosus. AB - A 13-year-old girl presented with abdominal pain, fever, dysuria, incontinence and pyuria and was subsequently diagnosed as having systemic lupus erythematosus (SLE) with extensive gastrointestinal involvement and an associated interstitial cystitis. Despite aggressive therapy with high dose prednisone and cyclophosphamide she developed a small bowel perforation and subsequently died. The combination of bowel symptoms and interstitial cystitis seems unique to the population with SLE, while the separate complication of bowel perforation carries an extremely poor prognosis in this group of patients. PMID- 1865425 TI - Large vessel vasculitis of the central nervous system in systemic lupus erythematosus: report and review of the literature. AB - Large vessel vasculitis rarely involves the central nervous system in patients with systemic lupus erythematosus. We describe an exemplary case, along with its dramatic cerebral angiogram, and review the literature on this unusual entity. PMID- 1865426 TI - Recurrent pericarditis and cardiac tamponade in a patient with hypocomplementemic urticarial vasculitis syndrome. AB - We describe a patient with hypocomplementemic urticarial vasculitis syndrome complicated by recurrent pericarditis and cardiac tamponade. The episodes of pericarditis were associated with urticarial vasculitis, hypocomplementemia, and circulating IgG antibodies to the collagen-like region of Clq. Histopathologic examination of the skin and pericardium demonstrated vasculitis associated with immunoglobulin and complement deposition suggesting an immune complex mediated etiology. Recurrent pericarditis should be included in the clinical spectrum of hypocomplementemic urticarial vasculitis syndrome. PMID- 1865427 TI - Cardiac manifestations of Weber-Christian disease: report and review of the literature. AB - A patient with chronic systemic Weber-Christian disease who was treated with hydroxychloroquine developed cardiac dilatation with congestive heart failure. Endomyocardial biopsy demonstrated myocyte degeneration and interstitial fibrosis, but no typical features of chloroquine induced cardiomyopathy. Clinical symptoms of congestive heart failure also were recognized in 7 of the 11 reported autopsy cases of Weber-Christian disease having cardiac involvement. This involvement can affect the pericardium and the myocardium. PMID- 1865428 TI - Diabetes insipidus secondary to Wegener's granulomatosis: report and review of the literature. AB - We describe a 51-year-old woman with Wegener's granulomatosis who developed diabetes insipidus 7 months after the onset of her granulomatous disease and despite apparently good clinical response to prednisone and trimethoprim sulphametoxazole treatment. A brain computerized tomographic scan taken soon after the onset of polyuria disclosed an enlarged pituitary gland that completely returned to its normal size after 5 months of cyclophosphamide therapy. We review 6 other published cases of diabetes insipidus secondary to Wegener's granulomatosis and discuss the potential pathogenetic mechanisms of this rare combination. PMID- 1865429 TI - Inner ear deafness in Wegener's granulomatosis. AB - Autoimmune deafness represents a heterogeneous group of disorders in which there is though to be inner ear and/or middle ear damage mediated by various immunological abnormalities. We describe a patient with Wegener's granulomatosis in whom there was evidence of significant inner ear damage caused by vasculitis, which was completely reversed by cyclophosphamide and prednisolone. We propose that Wegener's granulomatosis is a cause of autoimmune deafness. PMID- 1865430 TI - Fractures of the dens complicating ankylosing spondylitis with atlantooccipital fusion. AB - Patients with ankylosing spondylitis are prone to fractures. Fractures tend to occur in the lower cervical spine disc space. We describe 2 patients with odontoid fractures. Both patients had atlantooccipital fusion which may have increased their susceptibility for dens fractures. One patient had Crohn's disease. PMID- 1865431 TI - Common variable hypogammaglobulinemia presenting as nontypable Haemophilus influenzae septic arthritis in an adult. AB - Haemophilus influenzae is a rare cause of septic arthritis in adults. We describe a case of septic arthritis with nontypable Haemophilus influenzae presenting as the first invasive infection leading to a diagnosis of common variable hypogammaglobulinemia. Although nontypable strains have been shown to cause serious infections in adults, they are a rare cause of septic arthritis. Underlying immune deficiency should be considered in an adult who presents with invasive infection with Haemophilus influenzae, regardless of serotype. PMID- 1865432 TI - Mycobacterium gastri arthritis: septic arthritis due to Mycobacterium gastri in a patient with a renal transplant. AB - We describe an 18-year-old man with a renal transplant who developed septic metacarpophalangeal arthritis due to Mycobacterium gastri. He had several episodes of crystal induced synovitis, and treatment with intraarticular steroids was complicated 3 months later by iatrogenic septic arthritis. Appropriate treatment based on in vitro drug susceptibility was successful. This seems to be the first case of articular infection and the third report of human infection caused by this atypical mycobacteria. PMID- 1865433 TI - Scleroderma-like fasciitis without eosinophilia after L-tryptophan ingestion. AB - A 53-year-old man developed severe sclerodermatous skin changes and a neuromyopathic process, consistent with the eosinophilia-myalgia syndrome, 2 months after discontinuation of L-Tryptophan (L-Try). His peripheral eosinophil count was within normal limits upon presentation and remained so throughout the illness. Currently the Centers for Disease Control surveillance definition requires peripheral eosinophilia greater than 1000 cells/mm3. Eosinophilia myalgia syndrome may need to be part of a differential diagnosis even in the absence of peripheral eosinophilia. PMID- 1865434 TI - Concurrent use of folinic acid and MTX in rheumatoid arthritis. PMID- 1865435 TI - Changes in the marketing of methotrexate. PMID- 1865436 TI - IV methylprednisolone and nitrogen mustard. PMID- 1865437 TI - Systemic lupus erythematosus presenting as Salmonella enteritidis bacteremia. PMID- 1865438 TI - Hydroxyapatite pseudopodagra. PMID- 1865439 TI - Antineutrophil cytoplasmic antibodies in giant cell arteritis. PMID- 1865440 TI - Evaluation of the lateral flexion of the trunk. PMID- 1865441 TI - Epidermoid cancer of the anus--the surgeon retreats. PMID- 1865442 TI - Lipids in non-insulin dependent diabetes: a case for treatment? PMID- 1865443 TI - Anal cancer: the case for earlier diagnosis. AB - The results of treatment in 22 patients with anal carcinoma are reviewed. The overall results are disappointing with only five (28%) surviving more than 5 years. The commonest form of treatment during the study period was an abdomino perineal excision of rectum (APER). For patients with tumours less than 2 cm in diameter local excision is an acceptable alternative. The majority (76%) of tumours were diagnosed as common benign conditions by the referring practitioners leading to a delay in initiating definitive treatment. Most tumours (81%) were greater than 2 cm in diameter and therefore unsuitable for local excision. There was a high recurrence rate (76%) amongst the group treated by APER. This along with the poor overall survival is probably due to late presentation. PMID- 1865444 TI - Value of emergency cardiac enzymes: audit in a coronary care unit. AB - Medical audit in a district general hospital coronary care unit led to the introduction of an emergency cardiac enzyme service. 91.2% of patients eligible for thrombolysis therapy received treatment following this introduction compared to 73.7% before (P = .05). No patient was treated inappropriately on the basis of a raised cardiac enzyme. PMID- 1865445 TI - Cortical evoked response olfactometry. AB - An objective for the assessment of smell based upon olfactory cortical responses is introduced and illustrated with clinical examples. PMID- 1865446 TI - Should general practitioners refer more patients to hospital? AB - Twenty-two patients with skin problems were identified on the basis that their general practitioner was satisfied with their management and had no intention of referring them to hospital. These patients were reviewed by one of two dermatologists who made treatment recommendations in 14 cases, and these suggestions were taken up by 11 patients. Six patients reported definite subjective improvement in their skin condition six weeks later. The general practitioners found the consultation valuable in 17 cases. Although these patients might have improved without the dermatologists' intervention, a group of patients may exist who would benefit from specialist advice, even though that advice has not been sought. Restriction on hospital referrals could therefore be detrimental to patient care. Controlled trials could be conducted to determine the benefit of specialist advice on patients not currently seen in hospital. PMID- 1865447 TI - Waiting list initiatives: crisis management or targeting of resources? AB - To investigate the impact of a waiting list initiative on an ENT surgical waiting list, we have evaluated the outcome of the Tayside ENT Waiting List Initiative. Four hundred and forty-five patients were offered dates to come in during the initiative. Of these, 280 underwent surgery and 16 indicated that their operations were no longer necessary. The maximum wait for routine operations falling within the criteria for inclusion in the initiative was 28 months prior to the initiative can be effective in reducing waiting times for routine surgery. However, it is too early to describe the Tayside initiative as an unqualified success, as it remains to be seen whether or not the waiting list will lengthen again now that it is over. PMID- 1865448 TI - 'Skin failure'--a real entity: discussion paper. PMID- 1865449 TI - Liaison psychiatry for the 21st century: a review. AB - The development of liaison psychiatry services over the last 20 years is briefly reviewed--sophisticated liaison services have been confined to teaching hospitals. Limited manpower and other resources have prevented the development of liaison services in most district general hospitals; further developments are unlikely unless these deficiencies are corrected and psychiatrists take a more active role in developing links with physicians and surgeons. The time is right for such development as physicians are keen to extend our understanding of psychological and social factors in causing non-organic disorders, reduce unnecessary investigations and provide more comprehensive care. Increased collaboration between physicians and psychiatrists will provide a better service for many patients and this should be extended to all district general hospitals. PMID- 1865450 TI - Surveillance of disorders caused by occupational hazards--principles and practice: a review. PMID- 1865451 TI - An early 19th century view of the sympathetic ganglia. PMID- 1865452 TI - A contribution to the history of tuberculosis and leprosy in 19th century Norway. PMID- 1865453 TI - A question of principle. PMID- 1865454 TI - 'The strange mental state of an old man who thought he would be slaughtered'--an early report of dementia with delusion (1785). PMID- 1865455 TI - Subtle early features of onchocerciasis in a European. PMID- 1865456 TI - Insulin dependent diabetes mellitus and coeliac disease. PMID- 1865457 TI - Intestinal tuberculosis: an ongoing diagnostic dilemma. PMID- 1865458 TI - Massive lower gastrointestinal bleeding in association with the brown bowel syndrome. PMID- 1865459 TI - 5 q-syndrome and monoclonal gammopathy with alpha 1 antitrypsin deficiency. PMID- 1865460 TI - Subtotal colectomy following marathon running in a female patient. PMID- 1865461 TI - Accident flying squads. PMID- 1865462 TI - Gastrointestinal haemorrhage in the over 75s. PMID- 1865463 TI - Briquet's syndrome--some diagnostic considerations. PMID- 1865464 TI - Honey and healing. PMID- 1865465 TI - Immunology of the tonsils. PMID- 1865466 TI - Holoprosencephaly-polydactyly ('pseudotrisomy 13') syndrome: a syndrome with features of hydrolethalus and Smith-Lemli-Opitz syndromes. A collaborative multicentre study. AB - A syndrome of holoprosencephaly and postaxial polydactyly, associated with hydrocephalus, heart defect, adrenal hypoplasia, and other visceral malformations, has been observed in five unrelated children with normal chromosomes. Clinical overlap with lethal acrodysgenital dwarfism (Smith-Lemli Opitz syndrome type II) and hydrolethalus syndrome is discussed. Recessive inheritance seems likely. PMID- 1865467 TI - A convenient multiplex PCR system for the detection of dystrophin gene deletions: a comparative analysis with cDNA hybridisation shows mistypings by both methods. AB - Existing reactions for the multiplex PCR amplification of exons in the dystrophin gene have been modified to produce two multiplex reactions which separately cover the 5' and 3' major deletion 'hotspots' in the gene, and together detect approximately 98% of all deletions detectable by Southern cDNA hybridisation. A comparative study of 148 patients showed mistypings in both the cDNA hybridisation data (4%) and the PCR analysis (1.2%). We suggest means of circumventing the underlying problems in order to avoid mistyping and subsequent misdiagnosis, and conclude that, with appropriate precautions, multiplex PCR amplification can be the method of choice for detecting deletions in the dystrophin gene. PMID- 1865468 TI - Application of PCR amplification of DNA from paraffin embedded tissue sections to linkage analysis in familial retinoblastoma. AB - A family segregating for the retinoblastoma predisposition gene has been analysed using the polymerase chain reaction to exclude their son as being an affected gene carrier. The unusual feature of this family is that the affected child, who would ordinarily have been used to establish phase in a linkage study, died as a result of developing a second tumour some years ago. The only tissue available from this child was a paraffin embedded, formalin fixed histopathological specimen from the second tumour. It was possible to isolate DNA from this tissue and amplify the DNA flanking two polymorphic restriction enzyme sites to establish alleles which cosegregated with tumour predisposition. Archival material can now be used to offer families such as this prenatal screening to provide informed genetic counselling. PMID- 1865469 TI - What do young people think about screening for cystic fibrosis? AB - We investigated the knowledge of cystic fibrosis and the views about neonatal and carrier screening in 216 school students aged 14 to 16 years. This work was completed before the published identification of the cystic fibrosis gene in September 1989. Although initial knowledge of cystic fibrosis was low (only 17% of the students knew that the disease affected the lungs), there was good recall of basic information about cystic fibrosis and of recessive inheritance after a brief lecture. A total of 86% considered that carrier detection should be offered routinely and 88% felt that an offer of prenatal diagnosis for cystic fibrosis should be made if both prospective parents were known to be carriers. We believe that pilot studies of cystic fibrosis carrier screening in schools should be undertaken. PMID- 1865470 TI - Sweat testing to identify female carriers of X linked hypohidrotic ectodermal dysplasia. AB - X linked hypohidrotic ectodermal dysplasia (XHED) affects many epithelial functions, including sweat gland formation. Female carriers who manifest XHED may have defective dentition or a patchy distribution of sweating or both, as determined by starch and iodine sweat testing. Such sweat testing can be useful in assigning carrier status to at risk females in XHED families, and in obtaining an accurate diagnosis for isolated females who present with features of ectodermal dysplasia. The advantages of diagnosing female carriers of XHED include the optimisation of neonatal and paediatric care for affected male infants, who may be at substantial risk of death in infancy. PMID- 1865471 TI - Adult polycystic kidney disease in a kindred of West Indian origin exhibits linkage with the 3'HVR probe on chromosome 16. AB - In a large pedigree of Caribbean origin with adult polycystic kidney disease, linkage has been established to the 3'HVR probe on chromosome 16. Although there are five different fathers in this pedigree, only one of whom was available for DNA analysis, the polymorphic nature of 3'HVR has enabled gene tracking to be carried out. The same allele cosegregates with the disease in every affected family member. PMID- 1865472 TI - Somatic recombination may explain linear psoriasis. PMID- 1865473 TI - Coffin-Siris syndrome. PMID- 1865474 TI - Iris coloboma, ptosis, hypertelorism, and mental retardation: a new syndrome possibly localised on chromosome 2. AB - A patient with a phenotype resembling that of three children recently reported is described. His karyotype shows a pericentric inversion of chromosome 2, very similar to another child previously reported. We discuss the possibility that all these cases constitute a distinct syndrome. PMID- 1865475 TI - Infantile spinal muscular atrophy (SMA) and multiple congenital bone fractures in sibs: a lethal new syndrome. AB - Acute infantile spinal muscular atrophy (SMA type I, Werdnig-Hoffmann disease) has generally been accepted as an autosomal recessive disorder. However, several investigators have noted a slightly increased male to female ratio. We describe here a family with two affected male sibs who had a form of acute infantile SMA with congenital bone fractures, whose parents were first cousins. Pedigree analysis strongly suggested autosomal recessive inheritance, but X linked recessive inheritance could not be ruled out. In view of the heterogeneity of the SMAs, and the distinct clinical features found in our patients, we suggest that their infantile SMA might well be a distinct entity. We suggest that SMA I with congenital contractures and bone fractures appears to be a recognisable disorder that can be distinguished from the more common classic form of SMA I. PMID- 1865476 TI - Hypercoagulability in a patient with Marfan syndrome. AB - A 39 year old man with Marfan syndrome presented with multiple pulmonary emboli and renal, hepatic, and splenic infarcts of unknown aetiology. The combination of thromboemboli and physical features initially suggested homocystinuria; however, laboratory examination showed no evidence for this disorder. Laboratory evaluation identified no coagulation abnormalities. This patient represents the unusual occurrence of hypercoagulability in a patient with Marfan syndrome. PMID- 1865477 TI - Interstitial deletion of the long arm of chromosome 18, del(18)(q12.2q21.1): a report of three cases of an autosomal deletion with a mild phenotype. AB - We describe three unrelated patients with apparently identical interstitial deletions of the segment (18) (q12.2q21.1). They were a short and markedly mentally retarded 5 year old girl, a macrocephalic and obese 2 1/2 year old boy with moderate mental retardation, and a macrocephalic, severely mentally retarded 5 year old boy. Findings common to all five liveborn patients so far identified as carrying this deletion include a pattern of minor dysmorphic features (prominent forehead, ptosis of the upper eyelids, full periorbital tissue, epicanthic folds, strabismus), muscular hypotonia, seizures, behavioural disorders, and lack of major malformations. PMID- 1865478 TI - A new folate sensitive fragile site at 1p21.3. PMID- 1865479 TI - Prevalence of fragile X syndrome. PMID- 1865480 TI - HLA markers, hormones, and disease. PMID- 1865481 TI - Effect of clomiphene citrate upon periovulatory endometrial development in the baboon. AB - Endometrial histology in baboons (Papio cynocephalus anubis) was evaluated after five days of clomiphene citrate (CC) treatment initiated on either cycle day six (n = 8) or ten (n = 4). Biopsies performed before and after a human chorionic gonadotropin (hCG) induced ovulation were compared to non-CC treated controls. Although CC had a definite antiestrogenic effect on perineal skin, no significant effect of endometrial proliferation was demonstrable. PMID- 1865482 TI - Quantitation of serum immunoglobulins G, M, and A in the rhesus monkey (M. mulatta) using human monospecific antisera in the enzyme-linked immunosorbent assay: developmental aspects. AB - Using human monospecific antisera, several parameters have been optimized for the micro-ELISA "sandwich" technique used in the quantitative measurement of total serum IgG, IgM and IgA levels in rhesus monkeys. Representation of the optical density as a four-parameter logistic function provided excellent fits of the data over a wide choice of dilutions of human antisera used for coating the ELISA plates and for the peroxidase-conjugated antisera used in the system. The micro ELISA "sandwich" technique was shown to be specific, reliable, sensitive, and economical for use in the routine measurement of total serum IgG, IgM and IgA levels in the rhesus monkey. PMID- 1865483 TI - Serial estimates of body water content and distribution during the first postnatal month in baboons. AB - Water content of the various body compartments was estimated serially during the first postnatal month in six term baboon neonates. In absolute volumes (mL), total body water, intracellular water, and plasma volume all increased linearly with body weight and postnatal age, although the effect of weight was predominant. In proportion to body weight (mL/kg), total body water, intracellular water, and plasma volume increased linearly with postnatal age whereas extracellular water and red cell volume decreased. There was no linear relation between the proportions of any of the water volumes and body weight. PMID- 1865484 TI - Juvenile rheumatoid arthritis in a rhesus monkey (Macaca mulatta). AB - A juvenile rhesus macaque (Macaca mulatta) developed a symmetrical erosive polyarthritis involving both large and small diarthrodial joints. Neither an infectious nor a metabolic etiology could be determined. This case shares many clinical and pathological features with the polyarticular form of human juvenile rheumatoid arthritis. PMID- 1865485 TI - Preclinical toxicity study of a male injectable antifertility agent (styrene maleic anhydride) in rhesus monkeys, Macaca mulatta. AB - Polymer styrene maleic anhydride dissolved in dimethyl sulphoxide was injected intravasally to rhesus monkeys at the dose levels of 100 mg, 250 mg, and 500 mg in each vas deferens in low, high, and highest dose groups respectively, while control group received 0.5 ml DMSO in each vas deferens. The systemic toxicity study of the implant was carried out for 90 d. There had been no alteration in any of the toxicity parameters, ie, body weight, haematological, biochemical or histopathological, in the test animals as compared to control animals. Hence, it is concluded that the polymer SMA injected at above doses appears to be safe in our experiment. PMID- 1865486 TI - Technical note: a primatrail or an inexpensive cage expansion for group housing small primates. PMID- 1865487 TI - Dissecting the molecular mechanism of ion-solute cotransport: substrate specificity mutations in the putP gene affect the kinetics of proline transport. AB - Rare mutations that alter the substrate specificity of proline permease cluster in discrete regions of the putP gene, suggesting that they may replace amino acids at the active site of the enzyme. If putP substrate specificity mutations directly after the active site of proline permease, the mutants should show specific defects in the kinetics of proline transport. In order to test this prediction, we examined the kinetics of three putP substrate specificity mutants. One class of mutation increases the Km over 120 fold but only decreases the Vmax fourfold. Such Km mutants may be specifically defective in substrate recognition, thus identifying an amino acid critical for substrate binding. Another class of mutation decreases the Vmax 80-fold without changing the Km. Vmax mutants appear to alter the rate of substrate translocation without affecting the substrate binding site. The last class of mutation alters both the Km and Vmax of proline transport. These results indicate that substrate specificity mutations alter amino acids critical for Na+/proline symport. PMID- 1865488 TI - Single-channel K+ currents in Drosophila muscle and their pharmacological block. AB - Four types of nonvoltage-activated potassium channels in the body-wall muscles of Drosophila third instar larvae have been identified by the patch-clamp technique. Using the inside-out configuration, tetraethylammonium (TEA), Ba2+, and quinidine were applied to the cytoplasmic face of muscle membranes during steady-state channel activation. The four channels could be readily distinguished on the basis of their pharmacological sensitivities and physiological properties. The KST channel was the only type that was activated by stretch. It had a high unitary conductance (100 pS in symmetrical 130/130 mM KCl solution), was blocked by TEA (Kd approximately 35 mM), and was the most sensitive to Ba2+ (complete block at 10(-4) M). A Ca(2+)-activated potassium channel, KCF.72 pS (130/130) mM KCl), was gated open at greater than 10(-8) m Ca2+, was the least sensitive to Ba2+ Kd of approximately 3 mM) and TEA (Kd of approximately 100 mM), and was not affected by quinidine. K2 was a small conductance channel of 11 pS (130/2 KCl, pipette/bath), and was very sensitive to quinidine, being substantially blocked at 0.1 mM. It also exhibited a half block at approximately 0.3 mM Ba2+ and approximately 25 mM TEA. A fourth channel type, K3, was the most sensitive to TEA (half block less than 1 mM). It displayed a partial block to Ba2+ at 10 mM, but no block by 0.1 mM quinidine. The blocking effects of TEA, Ba2+ and quinidine were reversible in all channels studied. The actions of TEA and Ba2+ appeared qualitatively different: in all four channels, TEA reduced the apparent unitary conductance, whereas Ba2+ decreased channel open probability. PMID- 1865489 TI - Intracellular potassium activity in mammalian proximal tubule: effect of perturbations in transepithelial sodium transport. AB - Intracellular potassium activity (alpha Ki) was measured in control conditions in mid-cortical rabbit proximal convoluted tubule using two methods: (i) by determination of the K+ equilibrium potential (EK) using Ba(2+)-induced variations in the basolateral membrane potential (VBL) during transepithelial current injections and (ii) with double-barrel K-selective microelectrodes. Using the first method, the mean VBL was -48.5 +/- 3.2 mV (n = 16) and the mean EK was 78.4 +/- 4.1 mV corresponding to alpha Ki of 68.7 mM. With K-selective microelectrodes, VBL was -36.6 +/- 1.1 mV (n = 19), EK was -64.0 +/- 1.1 mV and alpha Ki averaged 40.6 +/- 1.7 mM. While these last EK and VBL values are significantly lower than the corresponding values obtained with the first method (P less than 0.001 and P less than 0.01, respectively), the electrochemical driving force for K transport across the basolateral membrane (microK = VBL-EK) is not significantly different for both techniques (30.1 +/- 3.3 mV for the first technique and 27.6 +/- 1.8 mV for ion-selective electrodes). This suggests an adequate functioning of the selective barrel but an underestimation of VBL by the reference barrel of the double-barrel microelectrode. Such double-barrel microelectrodes were used to measure temporal changes in alpha Ki and microK in different experimental conditions where Na reabsorption rate (JNa) was reduced. alpha Ki was shown to increase by 12.2 +/- 2.7 (n = 5) and 14.1 +/- 4.4 mM (n = 5), respectively, when JNa was reduced by omitting in the luminal perfusate: (i) 5.5 mM glucose and 6 mM alanine and (ii) glucose, alanine, other Na-cotransported solutes and 110 mM Na. In terms of the electrochemical driving force for K exit across the basolateral membrane, microK, a decrease of 5.4 +/- 2.0 mV (P less than 0.05, n = 5) was measured when glucose and alanine were omitted in the luminal perfusate while microK remained unchanged when JNa was more severely reduced (mean change = -1.7 +/- 2.1 mV, NS, n = 5). In the latter case, this means that the electrochemical driving force for K efflux across the basolateral membrane has not changed while both the active influx through the Na-K pump and the passive efflux in steady state are certainly reduced. If the main pathway for K transport is through the basolateral K conductance, this implies that this conductance must have decreased in the same proportion as that of the reduction in the Na-K pump activity. PMID- 1865490 TI - Labeling of adipocyte membranes by sulfo-N-succinimidyl derivatives of long-chain fatty acids: inhibition of fatty acid transport. AB - Sulfo-N-succinimidyl derivatives of the long-chain fatty acids, oleic and myristic, were synthesized and covalently reacted with isolated rat adipocytes. The plasma membrane proteins labeled by these compounds and the effect of labeling on the transport of long-chain fatty acids were investigated. Sulfo-N succinimidyl oleate (SSO) and myristate (SSM) inhibited the transport of fatty acids (by about 70%). Inhibition of fatty acid transport was not a result of alterations in cell integrity, as intracellular water volume was not changed. It did not reflect effects on fatty acid metabolism, since it was observed under conditions where greater than 90% of the fatty acid taken up was recovered in the free form. The inhibitory effect was specific to the fatty acid transport system, as the transport of glucose and the permeation of retinoic acid, a substance with structural similarities to long-chain fatty acids, were unaffected. Sulfosuccinimidyl oleate reacted exclusively with a plasma membrane protein with an apparent size of 85 kDa while sulfosuccinimidyl myristate also labeled a 75 kDa protein. These proteins were among the ones labeled by diisothiocyanodisulfonic acid (DIDS) which also inhibits fatty acid transport irreversibly. The data suggest that the 85-kDa protein, which is the only one labeled by all three inhibitors is involved in facilitating membrane permeation of long-chain fatty acids. PMID- 1865491 TI - Structural analogues of pyrroline 5-carboxylate specifically inhibit its uptake into cells. AB - Pyrroline 5-carboxylate, a naturally occurring intermediate, is a potent activator of redox-dependent metabolic pathways. The effect of pyrroline 5 carboxylate is due, at least in part, to the special mechanism mediating its entry into cells. Using Chinese hamster ovary cells we recently characterized the cellular uptake of pyrroline 5-carboxylate as a process transferring oxidizing potential pari passu with cell entry, a process consistent with group translocation. We sought to identify specific inhibitors to probe this unique uptake mechanism, to blockade the metabolic effects of pyrroline 5-carboxylate, and to provide strategies to identify the putative carrier protein. Because pyrroline 5-carboxylate, a ring structure with a tertiary nitrogen, is in spontaneous equilibrium with glutamic-gamma-semialdehyde, an open-chain structure, we tested analogues of both. Most open-chain aldehydes at 10 mM had little effect on the uptake of pyrroline 5-carboxylate. Although succinic semialdehyde did inhibit, its effect was nonspecific in that the uptake of alpha(methylamino) isobutyric acid was inhibited as much as the uptake of pyrroline 5-carboxylate. In contrast, pyrroline 2-carboxylate and other cyclic compounds with tertiary nitrogens, e.g., pyridines, were specific inhibitors of pyrroline 5-carboxylate uptake. Respective potencies of pyridine derivatives depended on the nature and location of constituent groups. Kinetics studies showed that these inhibitors were competitive with pyrroline 5-carboxylate and the most potent inhibitor, 2,6-pyridinedicarboxaldehyde, exhibited a K12 of 0.27 +/- 0.05 mM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865492 TI - Inability of Ehrlich ascites tumor cells to volume regulate following a hyperosmotic challenge. AB - Ehrlich cells shrink when the osmolality of the suspending medium is increased and behave, at least initially, as osmometers. Subsequent behavior depends on the nature of the hyperosmotic solute but in no case did the cells exhibit regulatory volume increase. With hyperosmotic NaCl an osmometric response was found and the resultant volume maintained relatively constant. Continuous shrinkage was observed, however, with sucrose-induced hyperosmolality. In both cases increasing osmolality from 300 to 500 mOSM initiated significant changes in cellular electrolyte content, as well as intracellular pH. This was brought about by activation of the Na+/H+ exchanger, the Na/K pump, the Na+ + K+ + 2Cl cotransporter and by loss of K+ via a Ba-sensitive pathway. The cotransporter in response to elevated [Cl-]i (approximately 100 mM) and/or the increase in the outwardly directed gradient of chemical potential for Na+, K+ and Cl-, mediated net loss of ions which accounted for cell shrinkage in the sucrose-containing medium. In hyperosmotic NaCl, however, the net Cl- flux was almost zero suggesting minimal net cotransport activity. We conclude that volume stability following cell shrinkage depends on the transmembrane gradient of chemical potential for [Na+ + K+ + Cl-], as well as the ratio of intra- to extracellular [Cl-]. Both factors appear to influence the activity of the cotransport pathway. PMID- 1865493 TI - Stereological estimation of the mean and variance of nuclear volume from vertical sections. AB - The application of assumption-free, unbiased stereological techniques for estimation of the volume-weighted mean nuclear volume, nuclear vv, from vertical sections of benign and malignant nuclear aggregates in melanocytic skin tumours is described. Combining sampling of nuclei with uniform probability in a physical disector and Cavalieri's direct estimator of volume, the unbiased, number weighted mean nuclear volume, nuclear vN, of the same benign and malignant nuclear populations is also estimated. Having obtained estimates of nuclear volume in both the volume- and number distribution of volume, a detailed investigation of nuclear size variability is possible. Benign and malignant nuclear populations show approximately the same relative variability with regard to nuclear volume, and the presented data are compatible with a simple size transformation from the smaller benign nuclei to the larger malignant nuclei. Finally, the variance in the volume distribution of nuclear volume is estimated by shape-independent estimates of the volume-weighted second moment of the nuclear volume, vv2, using both a manual and a computer-assisted approach. The working procedure for the description of 3-D size variability within benign and malignant nuclear populations can for all practical purposes be reduced to 2-D measurement of nuclear profile areas. These new powerful stereological estimators of nuclear volume and nuclear size variability provide an attractive approach to quantitative and reproducible malignancy grading of cancers. PMID- 1865494 TI - Study of potassium deficiency in cardiac muscle: quantitative X-ray microanalysis and cryotechniques. AB - An imbalance of potassium in cardiac muscle causes an alteration of heart function. The distribution and concentration of potassium in rat papillary heart muscle was studied using cryofixation and X-ray microanalysis. Freeze-dried cryosections and sections of freeze-dried, embedded tissue were analysed. Bulk frozen specimens were freeze-dried either in a vacuum or by a new technique using liquid propane as a cryodehydration medium. These two methods of freeze-drying were tested for elemental retention in other specimens, with comparable results. A potassium concentration of 120 mmol/l was measured in normal myocytes of cardiac papillary muscle compared to 80 mmol/l in myocytes of animals stressed by a temperature of 45 degrees C for 1 h. The presumed physiological significance of the findings is discussed. PMID- 1865495 TI - Comparison between the conventional method and the simple desiccation method in porcine sperm processing for scanning electron microscopy. AB - Sperm quality has been studied using different microscopic methods. Light microscopy gives similar percentages of sperm typologies (mature, immature and aberrant) as scanning electron microscope (SEM) techniques using both normal (critical-point drying) and simple desiccation techniques. Artefactual forms, which are easily recognizable, are not taken into account. The artefactual forms observed by the simple desiccation SEM method were spermatozoa with tails folded in a simple loop, and spermatozoa with short tails coiled at their extreme. The simple desiccation SEM method is a useful and rapid technique for the testing of porcine sperm quality. PMID- 1865496 TI - Alkaline hydrolysis/methylation-acetylation: a new technique for ultrastructural DNA cytochemistry. AB - A new technique for the visualization of DNA-containing structures in electron microscopy is described. Samples of glutaraldehyde-fixed bone marrow from rats were subjected to alkaline hydrolysis to remove RNA and the phosphate of phosphoproteins, followed by a combined blockage of protein carboxyl and amino groups through methylation-acetylation. After uranyl acetate staining of epoxy embedded ultrathin sections, chromatin from all cell types showed a highly selective and intense electron opacity. Staining methods for DNA were also positive in semithin sections. This simple procedure could be very useful in ultrastructural cytochemistry of DNA and chromatin. PMID- 1865497 TI - The African-American medical student: 1990 and beyond. PMID- 1865498 TI - Racism in the 1990s: old wine in a high-tech bottle. PMID- 1865499 TI - Cancer awareness among African Americans: a survey assessing race, social status, and occupation. AB - Knowledge of cancer prevention and control was defined in terms of prevention, etiology, treatment, symptoms, cancer rates, screening, and detection examinations. A survey of 86 African Americans and 68 white Americans in Alameda County, California was completed in 1985. An index comprised of 69 knowledge items was assessed. A multivariate analysis of race, education, socioeconomic status, and occupation confirmed that these characteristics were independent predictors of knowledge. Blue collar work status was the most important predictor of low knowledge levels. African Americans were less knowledgeable than white Americans with regard to diet in preventing cancer and treatment modalities for cancer, and were most likely to perceive surgery as contributing to metastases. Low education and income status predicted low levels of knowledge. An important consideration in changing knowledge levels is the need to translate technical information about treatment and metastases in ways that are effective in reaching target populations at risk for low levels of knowledge. Cancer prevention and control programs need to develop materials and strategies that are responsive to communities whose members are predominantly African Americans or blue collar workers, or have low levels of education and income. PMID- 1865500 TI - Trauma-adult respiratory distress syndrome. AB - Sixteen trauma victims with adult respiratory distress syndrome were retrospectively examined. High injury severity score (mean: 44), massive transfusion requirements, and prolonged ventilator days characterize this group. Persistent intra-abdominal infection accounted for two of three deaths in this series. Most of these patients were managed without paralysis using intermittent mandatory ventilation and positive-end expiratory pressure (PEEP). High frequency jet ventilation was necessary in one subject. Two patients exhibited early ARDS reversal, ie, clinical improvement, better chest x-ray and decreased shunt (within 72 hours) when an intra-abdominal septic focus was eradicated. Principles of critical care for these patients remain: an FiO2 less than .40, limiting barotrauma, using PEEP for alveolar recruitment and close monitoring of O2 transport. PMID- 1865501 TI - The effect of ethanol on bone mineral. AB - Chronic alcoholics frequently have osteopenia. This usually leads to an increase in long bone fractures. The exact cause of these changes is unknown. They could be caused by a change in the calcium metabolism or a change in the organic phase of bone. To elucidate the exact mechanism by which these changes occur, the following study was done. Forty-six Sprague-Dawley rats were divided into four groups. Two groups received alcohol, and two groups served as control. One set of each group received a fracture to the leg in order to study any change that might occur in the organic phase of bone. Our findings in these animals demonstrated that alcohol causes osteopenia due to a change in calcium metabolism and does not appear to effect the organic phase of bone. PMID- 1865502 TI - Risk of aortocoronary bypass surgery in a low-volume inner city hospital. AB - Incidence of coronary heart disease deaths has been reported to be higher in low socioeconomic groups compared to affluent subjects. In addition, a higher mortality rate has been reported at centers doing fewer open heart surgeries. This article presents evidence in variance with these convictions. We report a single team's experience with coronary artery surgery on 76 low socioeconomic, predominantly black patients (84%) over a period of 8 years. The volume of open heart surgery per year was less than 20. The overall mortality rate of 5.3%, infection rate of 1.3%, and perioperative infarction rate of 7.9% are not significantly different from the reported experience of high-volume surgical centers on similar patients during the same period. Thus, it is possible to obtain comparable results of myocardial revascularization surgery in low-volume, socioeconomically disadvantaged, inner city minority populations. PMID- 1865503 TI - Measures of renal function in patients with cisplatin-related chronic renal disease. AB - Twenty-seven patients with advanced stage refractory ovarian cancer were studied to determine if chronic stable cisplatin-related renal dysfunction was present. Medical histories were examined to determine the types of therapy previously received as well as the total previous platinum doses received that ranged from 200 to 2,100 mg/m2. Standard assessments of renal function were made prior to administering current chemotherapy or immunotherapy to the patient, which included 24-hour creatinine clearance, serum creatinine, and blood urea nitrogen (BUN). For patients with a 24-hour creatinine clearance of less than 60 mL/minute, serum creatinine was highly variable (range: 0.9 to 2.0 mg/dL) and was not related to the degree of diminution in the 24-hour creatinine clearance value. Conversely, for patients with a serum creatinine of less than 1.5, the 24 hour creatinine clearance values varied by almost three-fold, ranging between 46 and 120 mL/minute. Two patients with serum creatinines of less than 1 had creatinine clearances of less than 50 mL per minute. Similarly, BUN measurements did not correlate with 24-hour creatinine clearance values, and the 24-hour creatinine clearance value was not related to the total cumulative platinum dose. We conclude that patients who receive substantive doses of cisplatin may experience chronic stable cisplatin-related renal dysfunction and that serum creatinine cannot be relied on to assess the degree of renal compromise. In such patients, we recommended that the 24-hour creatinine clearance value should be used when medical management is influenced by renal function. PMID- 1865504 TI - Comparison of pulmonary tuberculosis in younger and elderly patients. AB - Pulmonary tuberculosis remains a significant clinical and public health problem in the elderly population. To describe age-related differences in disease manifestations, a comparison of the clinical features, predisposing factors, diagnostic approaches and radiographic findings in cases of pulmonary tuberculosis among 52 young and 62 elderly patients was performed. The elderly patients had a higher number of underlying disease than younger patients (p less than 0.05). Prior to admission, symptoms occurring with equal frequency in both younger and elderly patients included coughing, malaise, and weight loss. Elderly patients had significantly higher incidences of negative reactions to the PPD test (p less than 0.05). Radiographic findings revealed that upper lung field infiltrates were still common in both groups, but the elderly had more severe lung field involvement (two or more lobes affected), and more frequent pleural reactions than younger patients (p less than 0.05). Since there were non-specific clinical features, false negative skin test and complex radiographic manifestations, tuberculosis was frequently not suspected in the differential diagnosis, especially among elderly patients with multiple medical problems. We suggest that physicians need to have a high level of suspicion and awareness of varied manifestations for tuberculosis, especially elderly patients. PMID- 1865505 TI - Polymerase chain reaction technique for detection of human immunodeficiency virus type I. AB - A total of 7 cases were assayed by polymerase chain reaction (PCR) with an HIV-1 primer set matched the polymerase region. One homosexual man who was HIV-1 antibody negative was used as a negative control, the other cases included HIV-1 antibody positive asymptomatic, ARC and AIDS cases. The length of the amplified DNA segment was 115 base pairs (bp) and the appearance of this segment showed positive reaction with the HIV-1 antigen. These six HIV-1 antibody positive cases, including an asymptomatic infant showed a segment size of about 115 bp and were recognized as HIV-1 positive infections, and whereas the HIV-1 antibody negative case did not. PMID- 1865506 TI - Ocular refraction and its components among younger children in Kaohsiung: a 4 year longitudinal study. AB - A four-year longitudinal study was made on refraction and its components among 50 children of Kaohsiung, Taiwan, R.O.C. aged from 7 to 10.6 years. The methods of examination of the eyes were the same as that of four years ago, including Mydriacyl refraction, keratometry for corneal curvature radius, and ultrasonic measurement of the refractive components. One eye with amblyopia was excluded. The results of our study showed that all of our cases over 6 years of age had a corrected visual acuity of 0.8 or better, and that the refractive state shifted to myopia in our 4-year follow up. The rate of myopia increased from 2% to 27.3%. Comparisons of refractive components between the years 1983 and 1987 showed significant increases in refractive power, length of vitreous cavity and total axial length of the eyes. Corneal refractive power and lens thickness, however decreased significantly. As for differences in gender, several results were the same for both 1983 and 1987: corneal curvature radius, the length from anterior corneal surface to anterior lens surface, length of vitreous cavity and total axial length were larger in males than females. Finally, total axial length and corneal curvature radius were the factors most affecting the refractive state in younger children. PMID- 1865507 TI - Clinical efficacy of recombinant human erythropoietin in the treatment of anemia in hemodialysis patients: influence of dosing regimen, iron status, and serum aluminum. AB - To evaluate the clinical efficacy of recombinant human erythropoietin (EPO) and its influencing factors in the treatment of anemia in hemodialysis (HD) patients, 17 chronic stable HD patients (10 males, 7 females; mean age: 46.0 +/- 2.6 years) with severe anemia were enrolled in this study. The study period (ranging from 5 to 11 months) was divided into the initial 12 weeks of correction phase and the subsequent maintenance phase. EPO, 1500 U initially, was administered intravenously twice weekly (BIW group, n = 10) or thrice weekly (TIW group, n = 7) at the end of each HD. Dose was doubled every 4 weeks until up to a maximum dose of 6000 U if increment of hematocrit (Hct) was less than 3%. At the end of correction phase, anemia was markedly improved. Hct and hemoglobin (Hb) increased from 19.3 +/- 0.8 to 28.7 +/- 1.1% and from 6.5 +/- 0.3 to 9.6 +/- 0.4 g/dl, respectively. Fifteen patients (88%) reached to the target Hct of 30% at 13.7 +/- 1.2 weeks. At the end of study, Hct and Hb was maintained at 29.1 +/- 0.7% and 9.6 +/- 0.3 g/dl, respectively. Requirement of EPO dose to reach the target and maintain the stable Hct (greater than or equal to 28%) was 99 +/- 14 and 62 +/- 11 U/kg/week, respectively. Laboratory parameters showed that serum iron, transferrin saturation, sugar and triglyceride decreased significantly and uric acid and aluminum (Al) increased significantly. There was no significant change in predialysis blood pressure, body weight, cardiac ratio, and ECG. Quality of life was markedly improved with the better subjective feelings, physical activity and Karnorfsky index. Common adverse effects included exacerbated hypertension (23%), hyperphosphatemia (18%), hyperkalemia (18%), and flu-like syndrome (12%). All of them could be managed by medical and dialysis treatment. Investigation of influencing factors on response to EPO suggests that 1) TIW group had a better response than BIW group 2) Response was better in patients with more adequate iron status and less severe Al burden. 3) Time to target Hct correlated approximately with basal serum Al levels but did not correlate with basal serum parathyroid hormone levels. In conclusion, low dose of EPO therapy corrects anemia effectively with minimal adverse effects in HD patients. Dosing regimen, iron status, and serum Al will influence the response to EPO. PMID- 1865508 TI - [The relationship between functional recovery one year after a stroke, and related factors]. AB - This study examines the factors affecting functional performance of 40 hemiplegic subjects in their homes following discharge from the hospital. All subjects suffered a cerebral vascular accident at least one year prior to this research period. Barthel Index was used to assess subjects' self-reported functional level in activities of daily living (ADL). A backward elimination of stepwise regression analysis was performed to ascertain the predictive value of the variables in determining functional performance one year after the onset of a stroke. These variables are factors related to the initial onset and those affecting the patient's functional status at home. The results revealed that subjects who had a shorter length of stay in the hospital, scored a higher on the Barthel Index (p less than 0.05). It also demonstrated that subjects who were more satisfied with their current subjective health status, had a higher Barthel Index score. PMID- 1865509 TI - [Primary omental torsion--report of two cases]. AB - Primary omental torsion is a rare disease, with only two cases in the past four years reported at our hospital. The patients suffered from pains over the right lower quadrant region of the abdomen for 3 days. Physical examination showed tenderness and rebounding pain over the right lower quadrant region of the abdomen. Laboratory data revealed leucocytosis. Surgical intervention was performed under the initial impression of acute appendicitis. The surgery revealed omental torsion. The twisted omentum was smoothly, resected and the postoperative course was uneventful. We present these two cases and review the literature. PMID- 1865510 TI - Bacteriological quality and Escherichia coli resistance from downstream water source of Kao-Ping river in the period September 1990-January 1991. AB - Ten sites along the downstream of the Kao-Ping river were allocated for monitoring water pollution. A total of 120 water samples were collected during the period between September 1990 to January 1991. The membrane filtration technique was used to detect total coliform (TC), faecal coliform (FC) and faecal streptococci (FS). The pH value, temperature and conductivity of water sources were also recorded. The results revealed that mean water temperature was 24.3 degrees C, with weak basic (pH 7.5) and high conductivity (578.5 microS cm-1). Evidence of faecal pollution was seen throughout the study period. The geometric mean count per 100 ml water ranged from 32,398 to 87,876 for TC, from 20,443 to 44,244 for FC and from 1,354 to 4,774 for FS. Meanwhile, a total of 185 strains of Escherichia coli were tested for their resistance to antibiotics and heavy metal ions. The tested isolates exhibited a high level of resistance to tobramycin (46.5%), Pb (79.5%), As (73.5%) and Hg (71.4%). Most antibiotic resistance strains were found to be simultaneously resistant also to heavy metal ions. This study demonstrated that Kao-Ping river is heavily contaminated with faecal indicator bacteria. PMID- 1865511 TI - Can't find one AIDS vaccine? Try for a few! PMID- 1865512 TI - Defining, treating borderline hypertension continues to challenge clinicians, researchers. PMID- 1865513 TI - From the Food and Drug Administration. PMID- 1865514 TI - From the Surgeon General, US Public Health Service. PMID- 1865515 TI - A piece of my mind. House calls. PMID- 1865516 TI - Volunteer clinic caveats. PMID- 1865517 TI - Effects of outcome on physicians' judgment of appropriateness of care. PMID- 1865518 TI - Human factor IX for the treatment of hemophilia B. PMID- 1865519 TI - Questions about DNR orders. PMID- 1865520 TI - The subsequent risk of internal cancer with Bowen's disease. A population-based study. AB - OBJECTIVE: To address the subsequent risk of internal cancer in a population based cohort of patients with Bowen's disease. DESIGN: Incident cases of skin cancers other than malignant melanoma occurring in a defined population were classified as basal cell carcinoma, squamous cell carcinoma, or Bowen's disease. Through medical records, all patients were followed up for the development of subsequent internal cancer until they died, moved from Rochester, Minn, or January 1, 1986, whichever came first. Incidence rates of skin cancer and subsequent cancer were computed; the subsequent rate of internal cancer was compared with that prevailing in the community. PATIENTS: Enrolled were all permanent residents in the population base of Rochester, Minn, who developed basal cell carcinoma (n = 657), squamous cell carcinoma (n = 169), or Bowen's disease (n = 71) on the basis of pathologic examination and clinical presentation from 1976 through 1984. MAIN OUTCOME MEASURE: The relative risk of subsequent internal cancer among patients with Bowen's disease compared with that of the population base from which they arose was 1.1 (95% confidence limits, 0.5, 1.6). RESULTS: Annual incidence rates, adjusted to the 1980 US white population, were 14.9 per 100,000 for Bowen's disease, 38.8 for squamous cell carcinoma, and 146 for basal cell carcinoma. The estimated relative risk for subsequent cancer was 0.9 (95% confidence limits, 0.5, 1.6) among patients with squamous cell carcinoma and 1.0 (95% confidence limits, 0.7, 1.3) for patients with basal cell carcinoma. These risks were not significantly different for various durations of follow-up or for sun-exposed vs sun-protected sites. CONCLUSIONS: We find no evidence in these population-based cohort data of and increased risk of subsequent internal cancer associated with Bowen's disease or other forms of nonmelanomatous skin cancer. PMID- 1865521 TI - Limitations of listing specific medical interventions in advance directives. AB - Recent events, including the Cruzan decision and the passage of the Patient Self Determination Act, have renewed interest in the strengths and limitations of various types of advance directives. In one well-known approach, the competent person indicates preferences for or against a series of specific medical interventions that might be considered if the person loses decision-making capacity. However, such lists of interventions may shift attention away from overall treatment goals or may prescribe inappropriate medical care. Moreover, listing specific interventions in advance does not necessarily enhance self determination or reduce uncertainty in decision making. PMID- 1865522 TI - Management of hypertensive crises. AB - The availability of potent antihypertensive drugs that will decrease markedly elevated blood pressure within minutes to hours has changed the concepts of definition and therapy of hypertensive emergencies and urgencies. Intravenous infusion of sodium nitroprusside can be used in the truly emergent situation and is effective, reliable, and safe. While oral therapy is more convenient, it is not as consistently effective as parenteral administration and can lead to excessive reductions in blood pressure that are more difficult to manage than when short-acting agents are given intravenously. PMID- 1865523 TI - Use of animals in medical education. Council on Scientific Affairs, American Medical Association. AB - The use of animals in general medical education is essential. Although several adjuncts to the use of animals are available, none can completely replace the limited use of animals in the medical curriculum. Students should be made aware of an institution's policy on animal use in the curriculum before matriculation, and faculty should make clear to all students the learning objectives of any educational exercise that uses animals. The Council on Scientific Affairs recognizes the necessity for the responsible and humane treatment of animals and urges all medical school faculty members to discuss this moral and ethical imperative with their students. PMID- 1865524 TI - Free clinics. A solution that can work ... now! PMID- 1865525 TI - The double edge of knowledge. PMID- 1865526 TI - Thrombocytopenia during interferon alfa therapy. PMID- 1865527 TI - Military physicians train in civilian 'war'. PMID- 1865528 TI - Medical developments raise social, ethical issues. PMID- 1865529 TI - Rapid spread of pandemic in Asia dismays experts, spurs efforts to fight transmission. PMID- 1865530 TI - A sticky issue: HIV and the IVDU. PMID- 1865531 TI - Costs in dollars and lives continue to rise. PMID- 1865532 TI - From the Centers for Disease Control. Public Health Service report on fluoride benefits and risks. PMID- 1865533 TI - From the Centers for Disease Control. Cardiovascular disease, motor-vehicle related injury, and use of clinical preventive services--Behavioral Risk Factor Surveillance System, 1989. PMID- 1865534 TI - Fetal alcohol syndrome in adolescents and adults. PMID- 1865535 TI - Prophylaxis against Pneumocystis carinii pneumonia in children with HIV. PMID- 1865536 TI - The hypocholesterolemic effects of beta-glucan. PMID- 1865537 TI - The road to diagnostic certainty. PMID- 1865539 TI - Ehrlichia. PMID- 1865538 TI - Costs of low-osmolar contrast media. PMID- 1865540 TI - Patients who leave a public hospital emergency department without being seen by a physician. Causes and consequences. AB - OBJECTIVE: To determine whether patients who sought care at a public hospital emergency department and left without being seen by a physician needed immediate medical attention and whether they obtained care after leaving. DESIGN: Follow-up study of patients who left without being seen and of patients who waited to be seen by a physician. SETTING: A public hospital's emergency department in Torrance, Calif. PATIENTS: All patients who registered for care and left without being seen (n = 186) and a 20% random sample of patients who waited until they were seen (n = 211) in a 2-week period during spring 1990. MAIN OUTCOME MEASURES: At time of presentation: triage nurse urgency assessment, clinical acuity rating, and self-reported health status. At follow-up: hospitalization rates. RESULTS: Patients who left reported that they had waited 6.4 hours before leaving; those who stayed reported a 6.2-hour wait before being seen. There were no differences between those who left and those who stayed in chief complaint, triage nurse assessment, acuity ratings, or self-reported health status. Forty-six percent of those who left were judged to need immediate medical attention, and 29% needed care within 24 to 48 hours. Eleven percent of those who left were hospitalized within the next week, and three patients required emergency surgery. Nine percent of those who waited to be seen were hospitalized. Forty-nine percent of patients who left did not see a physician during the 1-week follow-up period. CONCLUSION: Overcrowding in this public hospital's emergency department restricts access to needed ambulatory medical care for the poor and uninsured. PMID- 1865541 TI - Consequences of queuing for care at a public hospital emergency department. AB - OBJECTIVE: To determine whether the length of a queue at a public hospital emergency department was associated with increased likelihood of patients' leaving without being seen by a physician and whether leaving adversely affected patients' health or affected their subsequent use of health care services. DESIGN: Observational cohort. Patients were surveyed during 1 week in July 1990 and received a follow-up survey 7 to 14 days later. The responses of patients who left without being seen by a physician were compared with those who were seen by a physician. SETTING: Emergency department at San Francisco (Calif) General Hospital. PATIENTS: All English-, Spanish-, and Cantonese-speaking adults waiting for emergency care were eligible. Of 882 eligible individuals, 700 agreed to participate; 85% of enrolled subjects saw a physician and 15% left without being seen. Demographic characteristics of patients who were and who were not seen were not significantly different. MAIN OUTCOME MEASURES: Emergency department waiting time and changes in patients' self-reported health. RESULTS: Patients were more likely to leave as waiting times increased. At follow-up, patients who left without being seen were twice as likely as those who were seen to report that their pain or the seriousness of their problem was worse. Only 4% of patients who left required subsequent hospitalization, but 27% returned to an emergency department. CONCLUSION: Many patients can appropriately decide whether their problem is truly urgent and make alternative plans in the face of long waits, but the health of some patients may be jeopardized by long queues for emergency care. PMID- 1865542 TI - A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group. AB - OBJECTIVE: To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals. PATIENTS: Hospitalized adults with signs of gram-negative infection and a systemic septic response. INTERVENTION: Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later. MAIN OUTCOME MEASURES: Mortality over the 30-day study period, resolution of organ failures, and safety. RESULTS: Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified. CONCLUSIONS: Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated. PMID- 1865543 TI - Changes over time in the knowledge base of practicing internists. AB - OBJECTIVE: To determine factors affecting the knowledge base of practicing internists. DESIGN: An 82-item multiple-choice examination with questions from the 1988 American Board of Internal Medicine (ABIM) certifying examination was used to assess the knowledge base of 289 internists. SETTING AND PARTICIPANTS: Participants were selected from among practicing internists in New York, New Jersey, and Pennsylvania who had received ABIM certification 5 to 15 years previously. RESULTS: significant inverse correlation (r = -.30) was found between examination scores and the number of years elapsed since certification. Knowledge declined sharply within 15 years of certification. In addition, procedure oriented subspecialists (cardiologists and gastroenterologists) had lower scores than other internists in this examination of general medical knowledge. Multivariate analyses showed that independent variables that predicted test performance were initial ABIM certifying examination score, time elapsed since certification, subspecialty classification, medical school type, and residency type. CONCLUSIONS: These results support the recent decision for time-limited certification of internists and raise questions related to content and standard setting for recertification examinations. PMID- 1865544 TI - British Columbia sends patients to Seattle for coronary artery surgery. Bypassing the queue in Canada. AB - Concern about waiting lists for elective procedures has become a highly visible challenge to the universal health insurance program in Canada. In response to lengthening queues for patients waiting for cardiac surgery, British Columbia made contracts with four Seattle hospitals to send a total of 200 patients for coronary artery bypass surgery. This article examines the cause of the queue for cardiac surgery in British Columbia and the events that led to outside contracting. Global hospital budgets and restrictions on capital expansion have limited hospital capacity for cardiac surgery. This constrained supply, combined with periodic shortages in critical care nurses and cardiac perfusion technologists, has resulted in a rapid increase in the waiting list. Reducing wide variations in the lengths of queues for individual surgeons may afford an opportunity to reduce long waits. While the patient queue for cardiac surgery has sparked a public debate about budget limits and health care needs, its clinical impact remains uncertain. PMID- 1865545 TI - Invasive group B streptococcal disease in adults. A population-based study in metropolitan Atlanta. AB - OBJECTIVE: To define the incidence and clinical spectrum of group B streptococcus infection in adults. To characterize groups at increased risk for infection. DESIGN: Retrospective population-based surveillance of group B streptococcus infections occurring in adults. Patients were identified by review of microbiology records at all surveillance area hospital laboratories. Demographic and clinical data were abstracted from patient medical records. SETTING: Metropolitan Atlanta, Ga, 1982 through 1983. PATIENTS: We identified 70 adult patients with invasive group B streptococcus infections; 14 infections occurred in pregnant women and 56 in nonpregnant adults. RESULTS: The annual incidence of group B streptococcus infection in men and nonpregnant women was 2.4 cases per 100,000 population. Incidence increased with age and was higher in blacks than in whites. The case-fatality rate was 32%. Group B streptococcus was most often isolated from blood (71%) and soft tissue (16%). Common clinical presentations included skin and soft-tissue infection (36%), bacteremia without focus (34%), pneumonia (11%), arthritis (9%), and endocarditis (9%). Compared with the general population's risk of infection, the risk of infection in persons with diabetes mellitus was increased 10.5-fold (95% confidence interval [CI], 7.8 to 14.4); in persons with cancer, it was increased 16.4-fold (95% CI, 11.5 to 23.3). CONCLUSIONS: Group B streptococcus infections cause serious disease in adults as well as in neonates, providing an additional rationale for vaccine development. Determining the incidence of adult disease and groups at greatest risk will help in focusing prevention efforts. PMID- 1865546 TI - The Maryland experience and a practical proposal to expand existing models in ambulatory primary care. AB - Two unique models for caring for the uninsured and underinsured are operating in Maryland. The first is a group practice, primary care model with a unique ambulatory Medicare waiver that has had a positive impact on patients and physicians. The second is a financial model--an all-payer prospective rate setting system for all critical care inpatient hospitals that, during a 13-year period from 1977 through 1989, has saved the citizens of the state approximately $5.361 billion, has allowed hospitals to provide $1.657 billion of charity care and bad debts, and has earned $517 million in net profits. The reasons for the success of each of the models are discussed and form the basis for a practical and politically feasible proposal: merge the best aspects of each model into an ambulatory primary care-based model financed through an all-payer prospective charge system. PMID- 1865547 TI - Too sick to wait. PMID- 1865548 TI - Monoclonal antibodies to endotoxin. New allies against sepsis? PMID- 1865549 TI - Sidney Wolfe, MD--healing the system or just raising hell? PMID- 1865550 TI - From the Office of the General Counsel. HIV-infected surgeons: Behringer v Medical Center. PMID- 1865551 TI - Effect of a taurine-supplemented diet on conjugated bile acids in biliary surgical patients. AB - The effect of a taurine-supplemented diet on the level of conjugated bile acids in postoperative patients was investigated during two consecutive 5-day period. Eighteen hepatobiliary patients with choledochostomies and a specific T-tube insertion were collected and divided randomly into two groups. In group 1, an ordinary postoperative soft diet was prescribed for the first 5 postoperative days and then followed with a taurine-supplemented soft diet (40 mumol/kg per day) for 5 consecutive days. In group 2, the taurine-supplemented diet was prescribed in reverse. At the end of the two periods, on days 5 and 10, bile was collected via a T-tube with an inflatable balloon and low-pressure motor suction. Analysis of conjugated bile acids was done by high-performance liquid chromatography. The results showed that a taurine-supplemented diet increased the concentration of taurocholic acid, glycocholic acid, taurochenodeoxycholic acid, glycochenodeoxycholic acid, and total bile acid from 0.5, 1.9, 0.3, 1.4, and 4.7 mg/mL (on day 5) to 1.1, 3.5, 1.0, 2.6, and 8.9 mg/mL, respectively, on day 10 in group 1. Similar findings were noted in group 2. These results indicate that a taurine-supplemented diet may enhance the conjugation and secretion of bile acid in hepatobiliary patients. PMID- 1865552 TI - Dietary manipulation of methotrexate-induced enterocolitis. AB - Administration of chemotherapy is limited by host toxicity, which is often manifested by severe enterocolitis. This study evaluated the effects of a liquid, elemental, chemically defined diet (ED) supplemented with 2% glutamine (Glu-ED) compared with a polypeptide diet (PPD) on the morbidity and mortality after methotrexate (MTX) administration. Fischer 344 rats (n = 80) were fed either a regular rat chow diet (RD), a 2% glycine supplemented elemental diet (Gly-ED), a 2% glutamine-supplemented elemental diet (GLU-ED), and a glycine-supplemented polypeptide diet(Gly-PPD) for 7 days prior to administration of MTX (20 mg/kg, ip). After 72 hours, eight rats per group were killed; portal vein and vena cava blood, mesenteric lymph nodes (MLN), liver, small intestine, and cecum were sampled for bacterial culture. Remaining animals were followed to calculate survival. One hundred percent of the Gly-PPD and 25% of the Glu-ED animals survived compared with 0% of the Gly-ED animals. Our data showed that ED resulted in an increased quantity of intestinal Gram-negative bacteria and diminished intestinal mucosal height and mucosal DNA/protein content. The polypeptide diet prevented intestinal mucosal atrophy, avoided MTX-induced enterocolitis and significantly improved animal survival compared with an elemental diet with or without glutamine supplementation. PMID- 1865553 TI - Comparative hypersensitivity in intravenous lipid emulsions. AB - We report a case of hypersensitivity to Intra-lipid but not to Liposyn II lipid emulsion. The patient had mild allergies to soybean protein, egg yolk, and egg whites by radioallergosorbent testing (RAST). Because protein contamination of the phospholipid binder during the emulsion manufacture may rarely occur, such contamination should be considered as a cause for urticarial eruptions associated with lipid emulsions. PMID- 1865554 TI - Selenium deficiency and cardiomyopathy in acquired immunodeficiency syndrome. AB - Selenium deficiency is common in patients with human immunodeficiency virus infection and may contribute to the development of cardiomyopathy. A 5-year-old boy with congenital human immunodeficiency virus infection developed cardiomyopathy. Evaluation for reversible causes of cardiomyopathy was notable for the diagnosis of selenium deficiency. Cardiac function improved on selenium supplementation. The role of selenium in cardiac dysfunction and the need for nutritional evaluation and supplementation of malnourished patients with acquired immunodeficiency syndrome is discussed. PMID- 1865555 TI - Vitamin K therapy in severe liver disease. AB - A middle-aged man with parenchymatous liver disease and a decrease in vitamin K dependent factors was given large doses of intravenous phylloquinone (10 mg/d for 20 days) without improvement in the synthesis of vitamin K-dependent factors. During subsequent liver transplantation, he exsanguinated. Although the exact role of over treatment with phylloquinone in this case is unclear, plasma levels of phylloquinone 300 times normal were attained after 5 days of treatment without effect on factors II, VII, IX, and X. Further therapy with vitamin K was unnecessary. PMID- 1865556 TI - Accessible pool and system parameters: assumptions and models. AB - Quantitative assessment of substrate metabolism from in vivo tracer kinetic data requires a model of the system, i.e., a hypothesis on the structure and functioning of the system. Some fundamentals of modeling important for studying intermediary metabolism in the steady state will be discussed. Accessible pool and system parameters are defined. Although the calculation of accessible pool parameters is structure-free, that of system parameters requires the use of non compartmental or compartmental structures. Assumptions, bases for choice, and relative merits of these two modeling strategies are discussed. Glucose and leucine metabolism serve as prototypes to illustrate the theoretical points. PMID- 1865557 TI - Empirical assessment of model validity. AB - The metabolism of amino acids is far more complicated than a 1- to 2-pool model. Yet, these simple models have been extensively used with many different isotopically labeled tracers to study protein metabolism. A tracer of leucine and measurement of leucine kinetics has been a favorite choice for following protein metabolism. However, administering a leucine tracer and following it in blood will not adequately reflect the complex multi-pool nature of the leucine system. Using the tracer enrichment of the ketoacid metabolite of leucine, alpha ketoisocaproate (KIC), to reflect intracellular events of leucine was an important improvement. Whether this approach is adequate to follow accurately leucine metabolism in vivo or not has not been tested. From data obtained using simultaneous administration of leucine and KIC tracers, we developed a 10-pool model of the in vivo leucine-KIC and bicarbonate kinetic system. Data from this model were compared with conventional measurements of leucine kinetics. The results from the 10-pool model agreed best with the simplified approach using a leucine tracer and measurement of KIC enrichment. PMID- 1865558 TI - Identifiability and parameter estimation. AB - In experiments on biological systems one often cannot measure all state variables (compartments). Given a particular experiment of that type, a basic kinetic parameter may have no effect on the observations; such a parameter is an insensible parameter for that experiment. A parameter may influence the observations and not be uniquely determinable; such a parameter is nonidentifiable for that experiment. Only identifiable parameters can be estimated uniquely, by that experiment. I review the basic theory to check identifiability for a nominal value of a parameter (local identifiability), and present some examples of problems that may arise in estimation. PMID- 1865559 TI - Noncompartmental analysis in metabolism. AB - A new type of model called a department is formulated to complement the compartment. While a compartment may be dominated by convective transport, a department is dominated by diffusive transport. Although exit from a compartment is limited by the rate of biophysical or biochemical removal ("kc"), exit from a department is limited by the rate of transport to the site of biophysical or biochemical removal. PMID- 1865560 TI - Role of modeling in the design of experiments in carbohydrate metabolism. AB - Most publications on modeling present only the final product without describing the details as to how they were developed and tested. It is, however, by model development and testing that the true power of modeling as a research tool reveals itself. The purpose of this paper is to present a "behind the scenes" look at a set of experiments designed to study carbon atom transport in gluconeogenesis. In particular, it will be shown how the development of one model led to hypotheses for which another set of experiments was designed. The model which resulted from the second study contained in turn a number of new hypotheses for which further experiments remain to be designed. The second model supported the findings of the first, and yielded deeper insights into the exchange of carbon atoms among three metabolites. It is hoped this illustration will encourage other investigators to take advantage of the utilitarian value of modeling not only as a parameter generating tool, but also as a true research tool which can aid significantly to extract more information from available data. PMID- 1865561 TI - Factors which regulate net hepatic glucose uptake in vivo. AB - The regulation of net hepatic glucose uptake in vivo occurs by way of the hormonal milieu (insulin and glucagon), the glucose level, and the route of glucose delivery. Hyperglycemia in the absence of changes in pancreatic hormones (i.e., increased insulin and/or decreased glucagon) does not elicit significant glucose uptake by the liver. Net hepatic glucose uptake is augmented in a dose dependent manner by a rise in insulin and is further stimulated by the presence of a "portal signal." The presence of coordinated changes in insulin, glucagon, and the glucose level in combination with the "portal signal" ensures adequate glucose uptake by the liver in response to a meal. PMID- 1865562 TI - Noninvasive approaches to tracing pathways in carbohydrate metabolism. AB - Compounds that can be given safely in large quantity, conjugate with intermediates of carbohydrate metabolism in liver, and are excreted, allow large amounts of those intermediates to be isolated noninvasively. By administering labeled compounds that form those intermediates and determining the amount and/or distribution of label in those intermediates, the metabolism of those compounds can be traced. Thus, glucuronide formation has been used to sample hepatic uridine diphosphate glucose (UDP-glucose) and study glycogen metabolism and the pentose pathway, phenylacetate to sample hepatic alpha-ketoglutarate and estimate relative flux through the Krebs cycle, and acetylation to sample hepatic acetyl CoA. Interpretations require knowledge of the anatomical sites of formation of the intermediates, since more than one pool of an intermediate can exist in liver. The extent the labeled compound is metabolized in extrahepatic tissues also must be taken into account. PMID- 1865563 TI - The liver and glycogen metabolism. AB - It was shown that the liver is not the major site of removal of glucose after a carbohydrate meal in man. Fractional extractions varied from 5 to 10%. Alternative substrates for postprandial hepatic glycogen synthesis were therefore sought. It was demonstrated than, in man, about 60% of hepatic glycogen was formed from gluconeogenetic substrates. Since significant excursions occur only in plasma lactate after glucose loading, this was deemed the most likely substrate under these circumstances. By differential sampling across the liver and the gut in a conscious pig model, it was found that the liver takes up enough lactate (fractional extraction of 40-50%) to account for the gluconeogenetic production of glycogen. Forty percent of this arises from the gut. Muscle (as represented by the forearm in man) does not contribute lactate during glucose loading, suggesting that other tissues such as the skin are of importance. The gluconeogenetic process may be an important site for the obligatory tissue production of lactate. PMID- 1865564 TI - Use of amino acid clamps to investigate the role of insulin in regulating protein breakdown in vivo. PMID- 1865565 TI - Leucine metabolism in man: lessons from modeling. AB - The metabolism of amino acids is far more complicated than a 1- to 2-pool model, yet, such simple models have been extensively used with many different isotopically labeled tracers to study protein metabolism. A tracer of leucine and measurement of leucine kinetics has been a favorite choice for following protein metabolism. However, administering a leucine tracer and following it in blood will not adequately reflect the complex, multi-pool nature of the leucine system. Using the tracer enrichment of the ketoacid metabolite of leucine, alpha ketoisocaproate (KIC), to reflect intracellular events of leucine was an important improvement. Whether this approach is adequate to follow accurately leucine metabolism in vivo or not has not been tested. From data obtained using simultaneous administration of leucine and KIC tracers, we developed a 10-pool model of the in vivo leucine-KIC and bicarbonate kinetic system. Data from this model were compared with conventional measurements of leucine kinetics. The results from the 10-pool model agreed best with the simplified approach using a leucine tracer and measurement of KIC enrichment. PMID- 1865566 TI - Determination of plasma-free fatty acid kinetics with tracers: methodologic considerations. AB - Plasma-free fatty acids (FFA) are an important source of energy for a variety of tissues. Recently, there has been an increased interest in the measurement of FFA kinetics in vivo, using radiolabeled or stable isotopic tracers. Standard techniques for measurement of FFA-specific activity are relatively imprecise and have limited sensitivity. We have developed a method for determination of the concentration and specific activity of individual plasma FFA that is precise (coefficient of variation less than 2%) and sensitive (detection limit in the high femptomolar to low picomolar range). Using this method, one can measure the kinetics of three or more long-chain fatty acids simultaneously. Its sensitivity is a particular advantage if one wishes to measure low rates of FFA turnover such as are encountered during hyperinsulinemia. It has been suggested that, for optimal accuracy in the determination of substrate kinetics, the tracer should be administered in the left ventricle and mixed venous blood samples should be obtained from the right heart. We have conducted experiments in dogs which demonstrate that peripheral tracer infusion and more conventional arterial (or arterialized venous) sampling actually provide more accurate estimates of FFA turnover; this is fortunate, since intracardiac infusion and sampling are not practical for human studies. PMID- 1865567 TI - Methods of investigating intestinal transport. AB - This article provides a brief overview of well-established in vivo and in vitro methods that have contributed the most to the understanding of transport processes across the gastrointestinal epithelium. In vivo perfusion techniques in humans revolve around double- and triple-lumen per oral tubes. In animals, in vivo techniques include the single and recirculation perfusion techniques and the double-isotope technique for measurement of net absorption. In vitro methods of studying intestinal transport include the everted gut sac technique, the Ussing chamber, the use of isolated epithelial cells, and the use of brush border and basolateral membranes isolated from enterocytes. The use of fluorescent probes for the measurement of intracellular ionic concentrations is a new and powerful in vivo technique that is now being applied to the gastrointestinal tract. PMID- 1865568 TI - Correlation between clinical features and deletions of the gene for dystrophin in Duchenne muscular dystrophy. AB - The clinical course and prognosis of Duchenne muscular dystrophy (DMD) was compared in patients with deletions of the gene for dystrophin (cDMD) and those without such deletions. A total of 24 patients was followed for at least 2 yrs. At age 12 the rating of the activities of daily life (ADL) and disease stage were less favorable in those patients with deletions of the gene for cDMD. At age 14, no difference in ADL and disease stage was observed between the two groups. The percent vital capacity was lower in those patients with the cDMD deficit. When the prognosis was evaluated by multivariate analysis of the data obtained at age 12, the percent of patients predicted as dying before the age of 20 was 40% for those without the cDMD deficit but 76% for those who were cDMD defective. None of the cDMD defective patients lived longer than 20 yrs, whereas 5 of 14 patients without the cDND deficit survived longer than 20 yrs. Disorders such as cardiac and respiratory failure were also seen more frequently in the cDND defective patients. These results suggest that patients with Duchenne muscular dystrophy with defective cDMD have more severe disease than those without cDMD deficit. PMID- 1865569 TI - Discrepancy between antiplatelet antibody activities detected by immunoblot procedure and platelet counts in idiopathic thrombocytopenic purpura. AB - By immunoblot procedure it is possible to identify the pathogenic autoantibody responsible for platelet destruction in idiopathic thrombocytopenic purpura (ITP). We assessed the relationship between antiplatelet antibody activities detected by this technique and clinical thrombocytopenia in a patient with ITP whose antiplatelet autoantibody was directed toward an 85-kDa antigen. In this patient, over a 2-year-period, the platelet counts were not correlated with the levels of antiplatelet autoantibody detected by immunoblotting. The present observations suggest that IgG autoantibody directed toward a specific antigen is not necessarily a critical determinant of the degree of thrombocytopenia, and that factors other than IgG-Fc-receptor-mediated platelet destruction are also important in the determination of the disease activity in ITP. PMID- 1865570 TI - Dihydroergotamine raises the level of serum growth hormone. PMID- 1865571 TI - Bucillamine may induce myasthenia gravis. PMID- 1865572 TI - Lymphocytic infiltrations in the lung of two autopsy cases with HTLV-I-associated myelopathy. AB - Pulmonary involvement in two autopsy cases with HTLV-I-associated myelopathy (HAM) was observed histopathologically and immunohistochemically. Case 1 was a 59 year-old woman who fell ill after having a blood transfusion, and died immediately of acute heart failure. Case 2, a 55-year-old man, died of pelvic tumor after a long period of steroid medication for the myelopathy. Histologically, in case 1, the submucosal stroma of bronchioles was thickened with T-lymphocyte infiltration. In addition, clusters of B-lymphocytes were aggregated beneath the epithelial layer of respiratory bronchiole; the alveolar septum was infiltrated with a few T-lymphocytes. Furthermore, many B-lymphocytes were aggregated in the submucosal stroma of large bronchi. On the other hand, obvious pathological changes were not seen in the lung tissues of case 2. The long period of steroid medication may account for the fewer findings in case 2. These results present the possibility that latent inflammatory changes develop in the lung of HAM patients, although clinical manifestations are not obvious, and that steroid therapy can modify those inflammatory changes. PMID- 1865573 TI - Primary aldosteronism with cortisol overproduction from bilateral multiple adrenal adenomas. AB - A 55-year-old woman with bilateral multiple adenomas showed hypertension, muscle weakness, hypokalemia, moon-like face and truncal obesity. Increased serum and urinary levels of aldosterone were observed. Serum cortisol level did not show a normal circadian rhythm. Microscopic examination of the resected tumors showed two types of adenoma cells; one (golden yellow tumor) was a large clear cell with foamy cytoplasm which possibly secreted aldosterone and the other (dark brown tumor) was an acidophilic cell with lipofuscin which might have produced cortisol. This is a very rare case of primary aldosteronism with Cushing's syndrome due to multiple bilateral adrenal adenomas. PMID- 1865574 TI - Pulmonary infiltrates with eosinophilia due to naproxen. AB - An increasing number of drugs have been implicated in the etiology of eosinophilic pneumonia characterized by the development of pulmonary infiltrates, and peripheral blood eosinophilia. Naproxen is a commonly used nonsteroidal anti inflammatory drug which may be added to the growing list of pharmacologic agents associated with infiltrative pulmonary lesions. A case of eosinophilic pneumonia induced by Naproxen is described. The results of TBLB, a lymphocyte stimulation test, and a challenge test supported this diagnosis. PMID- 1865575 TI - Renal failure due to cholesterol embolization following percutaneous transluminal renal angioplasty. AB - Percutaneous transluminal renal angioplasty was performed in a 63-year-old diabetic woman who had renovascular hypertension with solitary functioning kidney and diffuse atherosclerosis. Angioplasty was technically successful, while thereafter, fever and myalgia of legs occurred with gradual increases in blood urea nitrogen and creatinine. The patient became uremic over a month after angioplasty and was placed on dialysis. She died six months after angioplasty. Autopsy revealed cholesterol embolization in bilateral kidney, pancreas and spleen, causing subacute renal failure. It is suggested that careful assessment of the patient should be made when determining the need for renal angioplasty for renovascular hypertension with a solitary functioning kidney. PMID- 1865576 TI - A case of maternal subclinical Sjogren's syndrome associated with congenital heart block. AB - A case of subclinical Sjogren's syndrome was diagnosed when the patient delivered a baby with SSA antibody-positive congenital heart block (CHB). The mother had been asymptomatic throughout her life. The laboratory findings including sialography, lip biopsy, Schirmer's test and a Rose-Bengal test showed Sjogren's syndrome. Such an asymptomatic case is termed subclinical Sjogren's syndrome. Thus, it was important to investigate an asymptomatic mother who delivers a SSA antibody-positive CHB baby. PMID- 1865577 TI - Erythroleukemia and gastric cancer following thorotrast injection. AB - A 63-year-old male, who had undergone angiography using thorium dioxide (Thorotrast) at the age of 15 for investigation of a giant hemangioma on his left thigh, developed anemia in September 1986 (47 yrs after the angiography). A diagnosis of erythroleukemia was made from a bone marrow study which showed 56.4% megaloblastoid erythroblasts and 12.8% myeloblasts. Autopsy revealed Thorotrast deposition in the liver, spleen, bone marrow, and lymph nodes, and monotonous proliferation of myeloblasts in the bone marrow. He also had differentiated tubular adenocarcinoma of the posterior wall of the stomach. PMID- 1865578 TI - Hypophosphatasia in an adult: a case report. AB - In this rare case of adult hypophosphatasia, no radiological abnormalities of the skeletal system could be detected even by dual energy X-ray absorptiometry. Severe dental caries was the sole clinical manifestation, indicating this case as an "odontohypophosphatasia". The levels of serum osteocalcin were low, which may be a useful biochemical marker to diagnose hypophosphatasia. Southern blot analyses of the genomic DNA revealed no gross abnormalities. Thus, hypophosphatasia in this patient was presumed to be caused by point mutations or small deletions. In a review of previous reports, an increased incidence among women was found. PMID- 1865579 TI - Effect of glucagon infusion on renal hemodynamics in normal subjects and patients with chronic glomerulonephritis. AB - The effect of glucagon infusion (15-20 ng/kg/min, for one hour) on renal hemodynamics was examined in normal subjects and in patients with chronic glomerulonephritis (CGN). In normal subjects, the glomerular filtration rate (GFR) was significantly increased by glucagon with a concomitant rise in effective renal plasma flow (ERPF) and filtration fraction (FF) (GFR/ERPF). In renal patients with a baseline GFR of above 90 ml/min/l/73 m2, GFR was significantly increased in response to glucagon, without a significant rise in ERPF. The patients whose baseline GFR ranged from 40-90 ml/min had no significant increase in GFR, while ERPF rose significantly. These results suggest that the renal hemodynamic response to glucagon infusion were modified by the level of baseline GFR in patients with chronic glomerulonephritis. PMID- 1865580 TI - Pachydermoperiostosis with myelofibrosis and anemia: report of a case of anemia of multifactorial causes and its improvement with steroid pulse and iron therapy. AB - A 26-year-old male patient with pachydermoperiostosis is reported. He had severe anemia with myelofibrosis. Treatment with iron, prednisolone, oxymethorone and 1 alpha (OH)D3 were not satisfactory. But steroid pulse therapy with parenteral iron improved his anemia and pancytopenia, but was not sufficient to relieve the bone marrow fibrosis or splenomegaly. The mechanism of anemia which was considered to be multifactorial including gastro-intestinal bleeding associated with peptic ulcer or erosion and bone marrow failure due to myelofibrosis, is discussed. PMID- 1865581 TI - Renal manifestation of pustulosis palmaris et plantaris. AB - Diffuse proliferative glomerulonephritis without IgA deposits (DPGN) in patients with pustulosis palmaris et plantaris (PPP) is described. This association has not been previously reported. Although PPP was resolved transiently after tonsillectomy, it was worsened coincidently at the time of exacerbation of DPGN. Improvement of proteinuria and PPP was observed after antiplatelet therapy. It was suggested that the renal manifestation and the development of PPP were associated. PMID- 1865582 TI - A case of malignant hypertension and scleroderma after cosmetic surgery. AB - A 44-year-old woman with scleroderma-like skin lesions and malignant hypertension following mammoplasty is reported. Sclerotic change is an unusual finding for ordinary finding progressive systemic sclerosis. On admission, she had severe high-renin hypertension and progressive renal failure, suggesting scleroderma renal crisis. With intensive treatment for hypertension including angiotensin converting enzyme inhibitor, the blood pressure was well controlled. It was then suggested that she had malignant hypertension due to scleroderma after silicone injection, or the so-called human adjuvant disease after cosmetic surgery. PMID- 1865583 TI - Impaired neutralizing capacity of duodenal mucosa following luminal acidification in recurrent duodenal ulcer. AB - To investigate the role of the mucus-bicarbonate barrier in the prevention of duodenal ulcer recurrence, duodenal mucosal neutralizing capacity and mucosal prostaglandin (PG) synthesis were examined in 5 normal controls (NC) and 12 duodenal ulcer (DU) patients. DU patients were divided into non-recurrent (NR,7) and recurrent (R,5) groups based on endoscopic follow-up study. The recovery time (RT) was significantly longer and the mucosal PGE2 synthesis was significantly lower in R than in NC and NR groups. There was a proportional correlation between mucosal PG synthesis and RT in DU These results indicate that impaired neutralizing capacity caused by reduced endogenous PG synthesis in duodenal mucosa may contribute to recurrence of DU. PMID- 1865584 TI - A case of Trichosporon pullulans infection of the lung with adult T-cell leukemia. AB - Fungal infections are often reported, but Trichosporon infection is very rare. A 78-year-old man with adult T-cell leukemia complicated with pulmonary infections is presented. Bronchial exudate culture revealed many yeast-like colonies, which were morphologically and biochemically identified as Trichosporon pullulans. PMID- 1865585 TI - CA125-positive papillary tumor of the peritoneum. AB - A 71-year-old female visited our outpatient unit with chief complaints of anorexia and a sense of abdominal distension. The abnormalities found after admission were conspicious increases in CA125 levels in serum and ascites as well as anemia, accelerated erythrocyte sedimentation and increased serum LDH. The patient underwent an emergency operation for ileus. The histological diagnosis was serous papillomatous cancer. Immunohistologic staining of the cancer tissue demonstrated the production of CA125. In this very rare the remnant of the Mullerian duct in the peritoneum is thought to have been cancerous. PMID- 1865586 TI - A case of subarachnoid hemorrhage with electrocardiographic and echocardiographic changes simulating transmural myocardial infarction. AB - A patient with subarachnoid hemorrhage who exhibited changes suggestive of myocardial infarction by electro- and echocardiography and underwent coronary angiography is reported. Echocardiography demonstrated marked hypokinesis in the left ventricular anterior wall to the septum. Since the possibility of concomitant myocardial infarction could not be excluded, coronary angiography was performed with cerebral angiography. No abnormalities were observed in the coronary arteries, and the myocardial damage was considered to be due to subarachnoid hemorrhage. Echocardiograms showed improvements in left ventricular wall motion within a short time after operation of the intracranial lesion. PMID- 1865587 TI - Infective endocarditis of the tricuspid valve in a non-drug user. AB - A case of infective endocarditis of the tricuspid valve is described in a young female patient with no history of intravenous drug abuse. The patient suffered from symptoms of septic emboli of the lung and right heart failure. She was ultimately treated by tricuspid valve replacement. There was no recurrence of symptoms following surgery. PMID- 1865588 TI - Factor V deficiency in a patient with rheumatoid arthritis. AB - Factor V deficiency associated with rheumatoid arthritis was found in a 54-year old woman. Hereditary factor V deficiency is very rare; only about 150 cases have been reported since its discovery in 1943. This appears to be the first case report of factor V deficiency associated with rheumatoid arthritis in the literature. PMID- 1865589 TI - Hypopituitarism associated with Cogan's syndrome; high-dose glucocorticoid therapy reverses pituitary swelling. AB - A 70-year-old woman with Cogan's syndrome first presented with central diabetes insipidus and then developed secondary hypothyroidism. Magnetic resonance imaging revealed a diffuse pituitary swelling without evidence of tumor. High-dose glucocorticoid therapy administered to treat Cogan's syndrome was very effective in suppressing the inflammatory process, and resulted in the reversal of the pituitary swelling and partial recovery of thyroid stimulating hormone secretion. This is the first case of hypopituitarism associated with Cogan's syndrome, a form of autoimmune vasculitis. The glucocorticoid-responsive pituitary lesion is best explained by autoimmune hypophysitis which shows pituitary swelling and is known to often associate with other autoimmune phenomena. PMID- 1865590 TI - Painless myocardial infarction in identical diabetic twins. AB - A pair of 37-year-old identical twins with diabetes mellitus are described. One of the brothers was admitted for heart failure without pain, and autonomic neuropathy was found. The clinical diagnosis was inferior myocardial infarction with anteroseptal healed myocardial infarction. Cardiac catheterization revealed triple coronary vessel involvement. The diagnosis was confirmed at autopsy after sudden death. The other brother was also examined by cardiac catheterization, which revealed total right coronary occlusion and hypokinesis of the wall. There had been no previous pain nor upper body discomfort until that time in either twin. Thus, genetic factors should possibly be considered in the genesis of asymptomatic or silent myocardial infarction. PMID- 1865591 TI - Superior sagittal sinus thrombosis in blastic crisis of chronic myelogenous leukemia--a case report of a complete recovery. AB - Literature reviews have indicated that thrombotic complications in leukemic patients are rare that prompt diagnosis is very difficult, and that morbidity and mortality are extremely high. We describe the successful treatment of a 36-year old housewife suffering from chronic myelogenous leukemia with secondary myelofibrosis. PMID- 1865592 TI - Thyroid crisis associated with severe hypocalcemia. AB - A 30-year-old woman with thyroid crisis and impaired renal function presented with severe hypocalcemia. She had already had hypocalcemia one yr previously when her serum creatinine level was normal. A normal level of serum amino terminal fragment of parathyroid hormone in spite of severe hypocalcemia suggested impairment of parathyroid function. Since her serum magnesium was normal and she had no history of neck surgery or radioiodine therapy, her hypoparathyroidism was considered to be idiopathic. This is the seventh case with co-existing Graves' disease and idiopathic hypoparathyroidism reported in the literature. PMID- 1865593 TI - Parkinsonism in cerebrotendinous xanthomatosis. AB - This report describes a case of cerebrotendinous xanthomatosis (CTX) accompanied by clinical manifestations of parkinsonism, including oily and masked face, marked akinesia, muscle rigidity and resting hand tremor. Magnetic resonance imaging (MRI) of the brain showed high intensity areas on T2 weighted imaging, and slightly low intensity areas on T1 weighted imaging in the right globus pallidus and the left putamen. Cerebral cortical atrophy with slight ventricular dilatation and cerebellar atrophy were present as well. This is a case report of CTX which manifested parkinsonism. Parkinsonism may not be a coincidental manifestation in CTX, but rather represent a symptom of the same underlying diathesis. PMID- 1865594 TI - [Clinical features of 32 cases of fungal pneumonia]. AB - A total of 32 patients with mycoses other than cavity-formed aspergilloma were reviewed. The main pathogenic fungi were Aspergillus in 14, Candida in 8, Cryptococcus in 4, Trichosporon in 4 and Mucor in 2. Coinfection by two species was detected in 3 cases: Trichosporon and Aspergillus in 2 and Aspergillus and Candida in 1. The underlying diseases were hematologic malignancies in all cases except 1 case of lung cancer. The hematologic malignancies were mostly leukemias of various types. Cryptococcosis developed in patients given long-term corticosteroid treatment but not in leukemic patients. All cases of aspergillosis, candidiasis and mucormycosis were due to nosocomial infection. On the other hand, 3 of 4 cases of cryptococcosis or trichosporonosis were attributable to community-acquired infection. Two of 4 trichosporonosis cases were considered to have been acquired during 2-day home stays. The diagnosis of pulmonary mycosis was made pathologically in 18 and clinically in 14 cases. Of the latter, 6 cases had an air-crescent sign on chest X-ray films and 8 cases were culture-positive. Extrapulmonary involvement was seen in all 16 cases of candidiasis, cryptococcosis and trichosporonosis but not in 10 of 14 aspergillosis cases. Severe granulocytopenia was present in all cases except 4 cases of cryptococcosis and 3 cases of aspergillosis. Chest X-ray findings of aspergillosis were of two types: one was an air-crescent sign which was noted in the recovery phase from leukopenia and the other was gradually enlarging consolidation which was bound by the interlobar fissure and progressed to lobar penumonia. A diffuse granular shadow was not characteristic of any fungus species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865595 TI - [Upper airway finding on CT scan with and without nasal CPAP in obstructive sleep apnea patients]. AB - The area of upper airway (from the nasopharynx to the hypopharynx) was measured by means of computed tomography (CT) scan in 15 confirmed cases of obstructive sleep apnea (OSA) and in 4 normal controls while they were awake. The minimum cross-sectional area (MA) of the upper airway was 14.7 +/- 20.0 mm2 in OSA patients and 80.0 +/- 33.1 mm2 in normal controls and the difference was statistically significant (p less than 0.01). In OSA patients, MA did not correlate with age, body weight, apnea index, desaturation index, mean nadir-SO2 and lowest SO2. MA was also measured with OSA patients while nasal continuous positive airway pressure (NCPAP) of 10 cmH2O was applied and it was found that MA was significantly widened when NCPAP therapy was performed. We conclude that upper airway narrowing is consistent finding in OSA patients but the degree of narrowing does not correlate with parameters of apnea and gas exchange during sleep, and NCPAP is effective to widen the area of upper airway in OSA patients. PMID- 1865596 TI - [Changes of serum lipids and high density lipoprotein levels in patients with bronchial asthma]. AB - Serum lipid levels of 60 cases of bronchial asthma (males 30, females 30) were compared with 161 (males 91, females 70) controls. Serum cholesterol, triglyceride, Apo A1, A2, B, HDL-cholesterol (HDL-C), LDL VLDL, and atherosclerotic index (T-chol. HDL-chol/T-chol.) were measured. Asthma cases slowed low levels of serum cholesterol, triglyceride, LDL, VLDL and Apo B compared to the control group, while HDL-C, ApoA2 were higher than the control group. (p less than 0.05). The atherosclerotic index was low in the asthma group. A patient who had a 9-year history of asthma showed decreased HDL-C and increased T-cholesterol, on improvement of asthma attack and body weight loss. PMID- 1865597 TI - [Phase difference between chest flow and mouth flow during rest breathing in cases of pulmonary diseases]. AB - The phase difference between mouth flow and chest flow in cases of pulmonary diseases measured using a body box was compared with those in normal subjects. Phase differences in chronic pulmonary emphysema (CPE) and diffuse panbronchiolitis (DPB) patients increased compared to normal subjects, but remained normal in interstitial pneumonitis patients (Normal: 3.76 +/- 1.71, CPE: 10.70 +/- 4.93, DPB: 10.81 +/- 3.15, IP: 3.83 +/- 0.15 degrees). In addition, there was a good correlation with FEV1.0, FEV1.0% and RV/TLC (r: -0.634, -0.610 and 0.803). The analysis of phase differences during rest breathing is clinically useful because it is non-effort dependent and can evaluate the degree of airway disorders. PMID- 1865598 TI - [Clinical and physiological features of chronic pulmonary emphysema with paroxysmal dyspnea attacks masquerading as bronchial asthma--improvement of respiratory function after combination therapy of intravenous aminophylline and subcutaneous epinephrine following daily oral administration of prednisolone]. AB - Cases of chronic pulmonary emphysema accompanied with paroxysmal dyspnea attacks are often misdiagnosed as bronchial asthma. These patients repeatedly fall into a state of life-threatening respiratory failure. We must make an accurate diagnosis of emphysema to provide care of them. To clarify the possibility of doing this, we investigated the clinical and physiological features (primarily respiratory function) of emphysema. We observed twenty-five patients with chronic pulmonary emphysema and with chronic bronchial asthma, previously confirmed by selective alveolo-bronchogram (SAB); this technique reliably diagnoses emphysema, but often induces dyspnea attacks due to the stimulation resulting from intratracheal and intrabronchial procedures. In eight patients, chronic pulmonary emphysema was accompanied by an attack of paroxysmal wheezing and dyspnea; chronic pulmonary emphysema with wheezing (WPE). In eight other patients, chronic pulmonary emphysema was present without such attacks; usual pulmonary emphysema (UPE). In the final nine patients, chronic bronchial asthma (CBA) was present, while emphysema was ruled out by means of SAB. In all patients, we measured respiratory function before and after the combination therapy of intravenous aminophylline and subcutaneous epinephrine, which followed daily oral administration of prednisolone (PAE-treatment). In the WPE group, significant increases in measurement of various respiratory functions, including VC, RV, RV/TLC%, FVC, FEV1.0, PFR and V75 (p less than .05 excluded in FEV1.0 and PFR were p less than .01), were found after the PAE-treatment, compared with the values revealed before the treatment. In the UPE group, there were few changes PAE-treatment, compared with the values revealed before the treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865599 TI - [A case of T cell lymphoma of the lung]. AB - A 70-year-old woman complained of cough, sputum and fever. Chest roentgenogram showed a mass-like lesion with pleural effusion in the left thorax. Bronchoscopy revealed a polypoid lesion at the orifice of left B10 and mucosal swelling of the left lower lobe bronchi. The biopsied material of the polypoid lesion was diagnosed as malignant lymphoma (diffuse small cell type by LSG classification) and the immunohistochemical examination showed monoclonal proliferation of T lymphocytes. The atypical lymphocytes which were positive for T lymphocyte surface marker were detected in the pleural effusion. There was no evidence of metastasis in any part of the body under clinical examinations, and the lung was thought to be a primary site of the lymphoma. The doubling time of tumor was estimated to be 134 days. Four-drug combination chemotherapy resulted in a marked decrease of the tumor size. Immunohistochemical study to determine the subpopulation of lymphoma cells are required for diagnosis of pulmonary lymphoma, because the biological characters of T cell lymphoma might differ from those of B cell lymphoma. PMID- 1865600 TI - [A case of malignant pleural mesothelioma presenting as pneumothorax]. AB - The patient was a 51-year-old woman who had no history of asbestos exposure and showed left pneumothorax with a small amount of pleural effusion. On admission to our hospital, she showed clinical and laboratory data similar to that of spontaneous pneumothorax except for a high concentration of hyaluronic acid in pleural fluid. After treatment of pneumothorax, pleural effusion appeared to decrease on chest X-ray. After 3 months, however, pleural effusion again increased, in spite of the improvement of pneumothorax. The patient received open lung biopsy and the histological examination showed mixed type malignant pleural mesothelioma. PMID- 1865601 TI - [A case of multiple pulmonary arteriovenous fistulae associated with splenic abscess]. AB - A 51-year-old female was admitted with high grade fever, cyanosis and hypoxemia. The chest X-ray showed nodular shadows on bilateral lung fields. Beta streptococci were found on culture from the blood, and the fever fell after administration of both antibiotics and corticosteroid. Pulmonary angiography revealed four arteriovenous fistulae on bilateral lung fields. On abdominal ultrasonography and CT scan, a hypoechoic lesion with an irregular wall and varying internal echogenicity was detected within the spleen. This lesion changed in size and shape during the clinical course and diminished with improvement in the patient's condition. These findings were compatible with splenic abscess. Splenic abscess with pulmonary arteriovenous fistulae is rare. PMID- 1865602 TI - [A case of bronchiolitis obliterans organizing pneumonia, which recurred during prednisolone maintenance therapy]. AB - A 69-year-old man was admitted with general fatigue, dyspnea, cough, fever and right pulmonary infiltrations on a chest X-ray films. He had suffered from myocardial infarction 8 years before. Since September 1987, he had been given Aprindine in addition to previous drugs. In early November 1987, he developed dyspnea. Antibiotics were not effective. He was hospitalized on Nov. 13, '87 when crepitations were audible on his right chest. Methylprednisolone pulse therapy was effective, however right pneumothorax developed. He underwent right thoracotomy and lung biopsy. Lung biopsy specimens showed pathological features of bronchiolitis obliterans organizing pneumonia (BOOP). Corticosteroid therapy yielded a remarkable clinical, physiological and roentgenographic recovery. However, approximately two years later during prednisolone maintenance therapy, BOOP recurred. He responded again to corticosteroid treatment, however he died of hepatic failure on Dec. 17, '89. "Idiopathic" rather than "drug induced" was suggested for the cause of BOOP in this case. PMID- 1865603 TI - [A case of Klinefelter syndrome associated with lung cancer and RA lung]. AB - A 50-year-old man was admitted for evaluation of an abnormal shadow on a chest X ray. He had experienced pain and swelling in his fingers for three years. He had also noticed that he is impotent. The diagnosis of Klinefelter syndrome and rheumatoid arthritis (RA) was established by clinical findings and chromosomal analysis. Transbronchial biopsy revealed adenocarcinoma and right upper lobectomy was performed. Open lung biopsy showed interstitial pneumonia. In conclusion, we reported a rare case of lung cancer, rheumatoid arthritis and RA lung associated with Klinefelter syndrome. PMID- 1865604 TI - [A case of Kartagener's syndrome with bilateral superior vena cava and absent inferior vena cava]. AB - A 39-year-old man with a history of repeated attacks of acute bronchitis and pneumonia since childhood was admitted complaining of cough, sputum, and a high fever. A diagnosis of Kartagener's syndrome was made because of the presence of mirror-image dextrocardia with complete situs inversus, bronchiectasis in right B6 and B10, and chronic sinusitis. Examination of the ciliary ultrastructure of the bronchial epithelium showed defective inner dynein arms and impaired nasal clearance was suggested by the saccharin particle method. Contrast venography of great veins revealed a McCotter type II bilateral superior vena cava and an absent inferior vena cava with (hemi-) azygos continuation. A search to find a similar case in the literature failed. Abnormal ciliary movement from the embryonic period was implicated as a causative factor in Kartagener's triad and the morphological abnormalities of the great veins. PMID- 1865605 TI - [A case of CA19-9 producing adenocarcinoma of the lung associated with idiopathic interstitial pneumonia]. AB - A 63-year-old female, who had been suffering from idiopathic interstitial pneumonia (IIP) since two years and four months previously, was admitted with general fatigue, body weight loss, bloody sputum and progression of dyspnea. Chest roentgenogram on admission showed diffuse coarse ring shadows in the right middle and lower lung fields and in the left middle lung filed. Chest CT clearly showed honeycombing in bilateral dorso-basal segments of the lung. Serum CA19-9 level was elevated, and continued to increase during her clinical course. Sputum cytology was positive. Autopsy showed papillary adenocarcinoma of the lung (alveolar cell type). Immunohistochemical study of lung tissue showed positive CA19-9 staining on the surface of adenocarcinoma cells. PMID- 1865606 TI - This journal needs more research. PMID- 1865607 TI - Act now to implement nursing's agenda for health care reform. PMID- 1865608 TI - Information about SANE program is sought. PMID- 1865609 TI - Should there be a written policy on length of patient wait before discharge after administration of medications? PMID- 1865610 TI - A process for subsidizing the trauma nursing core course. PMID- 1865611 TI - Timber rattlesnake bite to the hand with secondary coagulopathy and serum sickness. PMID- 1865612 TI - A qualitative investigation of the use of humor by emergency personnel as a strategy for coping with stress. PMID- 1865613 TI - Implementing a new clinical coordinator role to facilitate primary care: one emergency department's experience. PMID- 1865614 TI - A two-part quality assurance project addressing infection rates of wounds sutured in the emergency department. AB - The process and outcome of our QA program suggest many areas for further examination; a study featuring a larger sample and more rigorous experimental research could address these. Our immediate goals, however--to examine the quality of wound care in our emergency department and to improve it--were accomplished. What is perhaps more important, this QA project made us look at our practice and realize that we could change things. We identified a problem, studied it, and did something about it. PMID- 1865615 TI - Ventricular fibrillation in a 2-month-old infant: a pediatric case study and review of lessons learned. AB - The best way to deal with pediatric patients in cardiac arrest is to be prepared. We often acknowledge that children may experience V fib, but we do not truly take to heart that those events with "less than 10% chance of occurrence" can happen to us. From this case, the pediatric resuscitation team concluded that it is necessary to be prepared for all possible cardiac arrest situations. I know that our ED staff is more prepared now that this unusual situation has happened to us. I hope that others will also reassess their hospital's ability to handle a pediatric arrest that is not related to a primary respiratory event. PMID- 1865616 TI - Emergency department care of the patient with an insulin pump. PMID- 1865617 TI - Starting intravenous lines in children. AB - Starting an IV line in children can be difficult. As with most skills, practice improves performance. However, a lack of practice for the clinician with otherwise good IV skills need not be an impediment. The suggestions described in this article can assist you in adapting your good IV technique to the pediatric patient. PMID- 1865618 TI - Preparing for pediatric emergencies. PMID- 1865619 TI - Law and the emergency nurse. Anything can happen! PMID- 1865620 TI - Emergency nursing in a baccalaureate program that uses a clinical preceptorship approach. PMID- 1865621 TI - Listen to the children. PMID- 1865622 TI - Innovative assessment of children's pain. PMID- 1865623 TI - Trauma site survey: emergency department preparation. PMID- 1865624 TI - A 57-year-old man with muscle spasms. PMID- 1865625 TI - An open letter to emergency nurses from a survivor of a major head injury. PMID- 1865626 TI - Deployed to Desert Storm: the first 40 hours. PMID- 1865627 TI - I didn't feel very tough. PMID- 1865628 TI - ENA sexual assault nurse examiners resource list. PMID- 1865629 TI - Annual listing of graduate programs offering emergency nursing or trauma-related nursing tracks. PMID- 1865630 TI - [ACE inhibition: mechanisms of "cardioprotection" in acute myocardial ischemia]. AB - Local inhibition of angiotensin-converting enzyme (ACE, kininase II) produces both-attenuation of angiotensin II generation and of bradykinin degradation. To delineate the participation of bradykinin in the cardioprotective actions of ACE inhibitors, experiments were performed in rats and dogs with cardiac ischemia reperfusion injuries. In isolated perfused working rat hearts with regional myocardial ischemia, bradykinin in concentrations as low as 1 x 10(-9) M increases coronary flow and reduces the incidence and duration of reperfusion ventricular fibrillation. In addition, enzyme activities of lactate dehydrogenase and creatine kinase as well as lactate output were decreased in the venous effluent of bradykinin-perfused hearts, which also showed improved cardiodynamic and metabolic parameters. Even concentrations of bradykinin lower than 1 x 10( 10) M, which were without influence on coronary flow, exerted comparable beneficial metabolic effects connected with reduced incidence and duration of ventricular fibrillation. Combined perfusions with threshold concentrations of bradykinin (1 x 10(-12) M) and the ACE inhibitor ramiprilat (2,58 x 10(-9) M), which were ineffective given alone, resulted in a marked cardioprotective effect. Perfusion with angiotensin II (1 x 10(-9) M) aggravated reperfusion arrhythmias and worsened myocardial metabolism. Bradykinin perfusion prevented this deterioration in a concentration-dependent manner. The bradykinin antagonist D Arg-[Hyp2, Thi5,8, D-Phe7]-bradykinin (1 x 10(-5)) completely abolished the cardioprotective effects of bradykinin or the ACE inhibitor. However, higher concentrations of bradykinin (1 x 10(-7) M) or ramiprilat (2,58 x 10(-5) M) reversed these properties of the bradykinin antagonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865631 TI - [Possibilities of ACE inhibitor therapy in acute myocardial ischemia]. AB - Acute myocardial ischemia results from an increased cardiac workload in presence of a critical coronary stenosis (demand ischemia), coronary occlusion (supply ischemia) or a combination of both. It is complicated by cardiac arrhythmias and deterioration of function of ischemic myocardium and results in an increased load and dilatation of non-ischemic myocardium. Cardiac protection in acute myocardial ischemia can be related to preservation of coronary blood flow, function of ischemic and non-ischemic myocardium or prevention of cardiac arrhythmias. In control animals and humans, ACE-inhibitors have no major effect on coronary blood flow. Myocardial ischemia raises plasma-renin-activity, angiotensin I-conversion by passage through coronary circulation, and plasma-angiotensin-II concentrations. ACE-inhibitors and angiotensin-II-receptor blockers increase coronary blood flow during myocardial ischemia. Other mechanisms (bradykinin potentiation) may be involved. We found a potentiation of the coronary dilatory effect of the neuropeptide neurotensin (which is probably mediated by prostaglandins) by ACE-inhibitor. ACE-inhibitor may delay infarct development in animal experiments and improve function of ischemic myocardium. The importance of early dilatation of non-ischemic myocardium is unknown and it is unclear whether it may be prevented by an ACE-inhibitor as was shown for late dilatation. Studies on the effect of ACE-inhibitors in exercise-induced angina pectoris are controversial. An antiischemic and coronary dilatory effect has been shown by invasive studies in patients. A preliminary study in unstable angina pectoris was positive. Beneficial hemodynamic and antiarrhythmic effects (as well as excessive hypotension, however) have been shown in patients with acute myocardial infarction. PMID- 1865632 TI - [ACE inhibition: mechanisms of cardioprotection in chronic heart failure]. AB - In the treatment of heart failure ACE inhibitors gained a unique position because of their beneficial effect on prognosis. The most likely explanation is their influence on factors that determine progression of the disease. These are: progressive deterioration of central hemodynamics, impairment of coronary perfusion, further activation of vasopressor systems, imbalance of sodium and water homeostasis and occurrence of malignant arrhythmias. ACE inhibitors have been shown to modulate these factors in a positive manner. In addition, they may also act by modulating factors, which may exert harmful effects on cardiac function in long term. These are: prevention and regression of the hypertrophy of the left ventricle as well as the media of resistance vessels, prevention of restenosis following PTCA, prevention of cyclosporin-induced premature coronary artery sclerosis, and correction of an impaired glucose metabolism. Whereas the positive effects of ACE inhibitors in the treatment of heart failure are well documented, their value for preventing heart failure has not been established, yet. PMID- 1865633 TI - [Renal effects of conversion enzyme inhibitors]. AB - Recently it has been recognized that even minor elevations of blood pressure contribute to progression of renal failure. Furthermore it has been documented that antihypertensive treatment retards progression of renal failure. Despite impressive experimental data firm clinical evidence, incontrovertible on biostatistical grounds, is not yet available to document that converting enzyme inhibitors (CEI) are superior to alternative antihypertensive agents with respect to halting progression. CEI undoubtedly reduce albuminuria, independent of their effect on systemic blood pressure, and this is related to alterations of glomerular permeability. Recent experimental data suggest that growth processes in damaged kidneys are an important aspect of progression. It is a fascinating perspective, but yet unproven, that CEI interfere with these processes. PMID- 1865634 TI - [ACE inhibition in heart failure and compromised kidney function]. AB - If ACE-inhibitors are considered for therapy in patients with heart failure, the actual renal function has to be taken into account. In patients with reduced intravascular volume, e.g. during therapy with diuretics, the renin-angiotensin system is activated. In this situation, the renin-angiotensin-system contributes to the maintenance of arterial blood pressure and glomerular filtration rate by angiotensin II mediated vasoconstriction in vas efferens and systemic circulation. A sudden complete inhibition of the renin-angiotensin system therefore may cause a pronounced decrease in blood pressure and a reduction in glomerular filtration rate (impaired renal excretory function). In patients with heart failure concomitant chronic renal failure, the use of ACE-inhibitors is without major risk; however, the clinical efficacy may be limited. This does not apply to patients with diabetes, where the risk for impairment of renal function is increased. The potential advantage of short acting ACE-inhibitors such as captopril may clinically be relevant only in patients with very advanced severe heart failure and low arterial pressure. In any case, it is recommended to start ACE-inhibitors with a low dose and withdraw diuretics one or two days before in order to restore the intravascular volume. PMID- 1865635 TI - [Changes in renal function in heart failure and their modification by conversion enzyme inhibitors]. AB - In congestive heart failure renal hemodynamics are characterized by a decrease of fractional renal blood flow (renal fraction of the cardiac output) and marked changes of the intrarenal circulation. The latter consists of cortical hypocirculation and an enhanced medullary blood flow in the presence of a relative rise in glomerular filtration rate (GFR). This compensatory increment of GFR is mediated by a stimulation of prostaglandins (dilatation of vas afferens) as well as the renin-angiotensin- and adrenergic systems (contraction of vas efferens). Therapy with ACE inhibitors influences renal function in a complex manner. A decline in GFR resulting in the worst case in acute renal failure (ARF) may be caused by two pathogenetic possibilities: 1. critical reduction in renal perfusion pressure (below 70 mm Hg) and/or 2. loss of the autoregulation of GFR by relaxation of the constricted vas efferens induced by stimulation of the renin angiotensin-systems (RAS). Activation of the RAS might be a consequence of severe renal hypocirculation as well as a diuretic induced volume and sodium depletion (contraction of the effective arterial blood volume). On the other hand, ACE inhibitors may improve renal blood flow and glomerular filtration rate. This may be due to a rise in cardiac output, dilatation of vas efferens and occasionally vas afferens and an increase of the ultrafiltration coefficient. The deterioration of renal function caused by ACE-inhibitors may be prevented by avoiding a volume and sodium deficit (withdrawal or reduction of diuretics) and careful titration of the ACE-inhibitor starting with lowest dosages. PMID- 1865636 TI - [Mechanisms of the development of the chronic phase of diseases of the small intestine]. AB - The results of studying mechanisms underlying chronicity of functional (chronic enteritis ) and severe organic (celiac disease) lesions of the small intestine have been analyzed. Mechanisms causing the diseases take a chronic course appeared very similar. They involve bacterial proliferation in the intestine with consequent impairment of the digestion, absorption and motility resultant in derangement of metabolism. Defects in protein and lipid metabolism proved most essential. Chronic enteritis is associated with a favorable outcome provided there are no grave malabsorption symptoms. Combined treatment as a rule produces good therapeutic response in chronic enteritis and celiac disease. Relevant schemes are presented. PMID- 1865637 TI - ["Non-ulcerative dyspepsia": its concept, clinical aspects, diagnosis and treatment]. AB - A conception of ++non-ulcerative dyspepsia is suggested. Relevant symptoms and their pathogenetic mechanisms are outlined. Basing on clinical aspects, separate forms of the syndrome, therapeutic and diagnostic approaches to each of the forms with special emphasis on pilot chemotherapy are considered. PMID- 1865638 TI - [Hospital mortality in myocardial infarction]. AB - The author considers the results of conservative treatment of 9709 patients who received continuous intravenous drip nitroglycerin as a component of the basic therapy. For these patients hospital lethality amounted to 17.5%. The lethality in shown to vary with sex, age, infarction extent, primary or repeated occurrence. The results obtained were compared to those from other institutions. It is believed that hospital lethality standards should not be inappropriately overstated. PMID- 1865639 TI - [Current concepts of the pathogenesis of cholelithiasis]. PMID- 1865640 TI - [Cardiac insufficiency]. PMID- 1865641 TI - [Did Pechorin have Gilbert's disease? Reconstruction of the diagnosis based on the literary text]. PMID- 1865642 TI - [Atypical and combined forms of infectious-allergic polyneuropathies]. PMID- 1865643 TI - [Famotidine--a new histamine H2 receptor blockader]. PMID- 1865644 TI - [Chemotherapy of portal hypertension]. PMID- 1865645 TI - [Problems of classification of lymphoproliferative disorders]. PMID- 1865646 TI - [Clinical and social factors of resuming work by patients with ischemic heart disease after aortocoronary bypass]. AB - In spite of the fact that clinical condition in 85.6% of coronary patients subjected to aortocoronary shunting has improved against their preoperative status, only 43.3% of them resume work. Invalidity in these patients increases two-fold mounting to 94.4%. The causes of the discrepancy between the expected and real performance are scrutinized with due consideration of clinical and social factors essential for the patients' decision to resume or give up work. PMID- 1865647 TI - [Work capacity of patients with heart aneurysm after surgical treatment]. PMID- 1865648 TI - [Thrombolytic therapy in acute myocardial infarction at the pre-hospital stage]. AB - Mobile teams of the Leningrad Emergency Station came to use prehospital thrombolytic therapy (TT) for acute myocardial infarction (AMI) in 1986. The trial reported includes three groups of AMI patients: group I of 67 patients received avelysin in a dose of 0.5 mln FU, group II of 35 patients received celyase in a dose of 1 mln FU, group III consisted of 47 control subjects. The analysis of the treatment results showed that intravenous infusion of avelysin enabled myocardial reperfusion in 49.3% of cases while that of celyase in 5.7% (noninvasive data). High effectiveness of avelysin is inferred as well as safety of systemic TT at prehospital stage of AMI. PMID- 1865649 TI - [Unstable stenocardia: prognostic significance of painless forms of myocardial ischemia during hospitalization and in the remote period]. AB - Variants of unstable angina pectoris were compared upon examination of 366 relevant patients. 24-h ECG monitoring registered painless ST shifts in 75 of them. Treatment at hospital produced results independent of ischemia form (painful or painless). However, the analysis of long-term response for 10 patients demonstrating episodes of ischemia at discharge suggests that in spite of numerous adjustments of treatment in 70% of the patients the risk of unfavorable outcome seems great. PMID- 1865650 TI - [Hyperproduction of immunoglobulin E in occlusive diseases of the peripheral arteries]. PMID- 1865651 TI - [Prevalence of cough as a predictor and symptom of chronic bronchitis among male population of Kharkov]. AB - A questionnaire survey using WHO-recommended unified questionnaires was performed in Kharkov to elucidate the role of short-term (less than 3 months yearly) and long-term (greater than 3 months, per 2 years) cough in prediction and diagnosis of chronic bronchitis. Cough prevalence was investigated in 5-year age groups (40 44, 45-49, 50-54, 55-59) and correlated to education level and risk of chronic noninfectious diseases. The study covered a population of 7901 males at the mean age of 49 +/- 2.3 years. A group of active prophylaxis and two reference groups comprised 2001 males from an open population. The trial revealed an increase in cough incidence for smokers, low-educated and aged examinees. It is suggested that social and economic status dependent on educational level may represent a risk of chronic bronchitis not less than occupation, smoking, etc. PMID- 1865652 TI - [Enterosorption and therapeutic fasting in the treatment of patients with bronchial asthma]. AB - To rise the effectiveness of the treatment and reduce its duration as well as to out acidosis, 18 patients with bronchial asthma and chronic obstructive bronchitis were treated by fasting diet and enterosorption. The scheme of the diet was conventional, with intake of SKNP-2 enterosorbent in daily dose 30-60 ml throughout the fasting. The combination of the two treatment methods appeared effective, fasting-related acidosis was not recorded. PMID- 1865653 TI - [Use of chlotazol as an immunomodulating agent in chronic bronchitis]. AB - A positive immunomodulatory effect was found in chronic bronchitis patients examined immunologically before and after treatment including chlotazol. T- and B cell immunity recovered, clinical condition of the patients improved. A combination of known antimicrobial and antiinflammatory effects with an uncovered immunomodulatory one made chlotazol a valuable modality in the treatment of chronic bronchitis associated with secondary immune deficiency. PMID- 1865654 TI - [Surface hepatitis B- and delta antigens in the liver of patients with chronic active hepatitis]. PMID- 1865655 TI - [Diagnostic and prognostic significance of anti-HBCAG IgM in hepatitis B and its outcomes]. AB - Enzyme immunoassay was employed to investigate HBV markers (HBsAg, HBeAg, IgM anti-HBc, anti-HBc, anti-HBs) in 126 patients suffering from viral hepatitis B. It was noted that IgM anti-HBc appeared in ++pre-jaundice period in 100% of the examinees. In case of hepatitis transformation into a chronic form the titers of IgM anti-HBc depended on the disease activity, their high concentration being typical for the stage of active virus replication. PMID- 1865656 TI - [Differential diagnosis of myocardiodystrophies of different etiologies]. PMID- 1865657 TI - [Immunoglobulin E level in acute Yersinia infection]. AB - IgG, IgE, IgA, IgM levels were measured in patients with yersiniosis (generalized or mixed variant). Acute period of the disease (week 1-2) was associated with elevated levels of IgE in 59.1% of the patients which returned to normal on week 4-6. Time course changes in IgA, IgG and IgM concentrations were related to the synthesis of specific antibodies. IgE level rise can be considered a defence mechanism contributing to elimination of yersinia antigens from the body. PMID- 1865658 TI - [Fibrinolysis as a cause of coagulopathy in patients with chronic diffuse diseases of the liver]. AB - Examination was performed of 74 patients with chronic diffuse diseases of the liver; chronic active hepatitis, compensated hepatitis, decompensated cirrhosis of the liver (26, 28, 20 patients, respectively). Fibrinolysis was evaluated in relation to its effect on hemocoagulation. It appeared the principal cause of coagulopathy in 3% of the examinees. It is stated that activated fibrinolysis in chronic diffuse diseases of the liver underlies coagulopathy in few patients with decompensated cirrhosis, in compensated hepatopathy the influence of fibrinolysis on overall coagulative capacity of peripheral blood is insignificant. PMID- 1865659 TI - [Examination of carriers of biological false positive results of serological reactions to syphilis]. PMID- 1865660 TI - [Accelerated erythrocyte sedimentation syndrome]. AB - Accelerated erythrocyte sedimentation rate detected in 59 patients was a cause of their hospitalization and close examination. It revealed tumors, soft tissue and vessel inflammation, hematologic disorders with M-gradient found at blood protein electrophoresis, disseminated atheromatosis. The cause of the syndrome was not identified in 3 cases. PMID- 1865661 TI - [Status of phosphorus-calcium metabolism and the bone system in diffuse-toxic goiter]. PMID- 1865662 TI - [Effect of pathogenetic treatment on vasopressin secretion in patients with hypothalamic syndrome]. AB - Blood vasopressin concentration, hypothalamic response to stress resultant from insulin hypoglycemia and to acute furosemide load were measured in 72 patients with neuro-endocrine-metabolic form of hypothalamic syndrome. Pathogenetic treatment was decided upon by sensitivity to dopaminergic drug parlodel and antiserotonin drug peritol. According to the sensitivity tests the patients received either parlodel (5 mg/day) or peritol (12 mg/day) for 3-6 months. There were also patients on symptomatic treatment aimed at reduction of body weight. Peritol treatment promoted a decline in basal blood level of vasopressin and better response to insulin hypoglycemia and furosemide test. Parlodel treatment normalized vasopressin blood concentration and hypothalamic response to stimulators. Routine symptomatic therapy did not induce differences in vasopressin level compared to active stage of the disease. PMID- 1865663 TI - [Laser therapy of stomach and duodenal ulcers]. PMID- 1865664 TI - [Gaucher's disease]. AB - Two cases of Gaucher's disease are described. The diagnosis was based on clinical appearance, observation of the typical cells in the sternal and splenic puncture biopsies. Leucocytic beta-glucocerebrosidase activity was found inhibited in contrast to normal activity of the other lysosomal glycosidases. A female of 51 developed significant changes in the bones, progressive enlargement of the liver, chronic calculous cholecystitis 36 years after splenectomy. Current aspects of pathogenesis, clinical symptoms, diagnosis and treatment of Gaucher's disease are reviewed. PMID- 1865665 TI - [Pathogenesis and treatment of abdominal pain spinal syndrome]. AB - Development of the abdominal pain spinal syndrome is due to alterations in motor segments of the low-thoracic spine which bring about compression and dyscirculatory shifts in the nervous roots and their vegetative branches. Manual therapy was successful in recovery of physiological coordination between elements of the spinal motor segment thus correcting abnormalities in the nervous roots related to compression and affected circulation in 30 out of 36 patients treated. PMID- 1865666 TI - [Peutz-Jeghers syndrome]. PMID- 1865667 TI - [A case of candidiasis in a patient with chronic fungal infection, secondary immunodeficiency and Cushing's syndrome]. PMID- 1865668 TI - [Splenic infarction as a cause of suppurative peritonitis and septicemia]. PMID- 1865669 TI - [Horton's disease]. PMID- 1865670 TI - [Hemochromatosis associated with polyserositis]. PMID- 1865671 TI - [Painless myocardial ischemia]. PMID- 1865672 TI - Changes in blood rheologic factors following coronary artery surgery. AB - Blood rheologic parameters were examined in 16 patients without multiple organ failure 2 weeks after coronary artery surgery. The whole blood viscosity (shear rate = 94.5 sec-1) was unchanged (4.59 +/- 0.53 to 4.56 +/- 0.58 mPa.s) despite a significant decrease in hematocrit (39.8 +/- 4.3 to 37.1 +/- 3.8%, P less than 0.05). The oxygen delivery index (the ratio of hematocrit to whole blood viscosity) was significantly decreased (8.67 +/- 0.35 to 8.18 +/- 0.59%/mPa.s, P less than 0.05). Plasma viscosity (shear rate = 94.5 sec-1) increased significantly (1.60 +/- 0.13 to 1.72 +/- 0.10 mPa.s, P less than 0.01), as did serum levels of globulin (2.8 +/- 0.4 to 3.0 +/- 0.4 g/dl, P less than 0.01), alpha 1-antitrypsin (232 +/- 41 to 308 +/- 60 mg/dl, P less than 0.001), and fibrinogen (381 +/- 81 to 479 +/- 117 mg/dl, P less than 0.001). Total protein and globulin levels showed a good correlation with plasma viscosity, but the fibrinogen concentration demonstrated no correlation. The passage time of a 40% red blood cell suspension (0.5 ml) was shortened significantly from 10.2 +/- 1.1 to 9.2 +/- 1.0 sec (P less than 0.05). These results indicate that an increase in plasma viscosity is important in determining blood rheologic properties 2 weeks after coronary artery surgery. PMID- 1865673 TI - Neonatal myocardium resists reperfusion injury. AB - The response of neonatal myocardium to ischemia and reperfusion was observed in an isolated working heart model using neonatal rabbits and compared to that of the adult rabbit heart. Lipid peroxidation occurring during ischemia and that occurring during reperfusion were evaluated separately. Malondialdehyde (MDA) in heart tissue was measured as an index of lipid peroxidation, and the occurrence of oxygen free radical damage was assessed by the effects of the scavengers, superoxide dismutase and catalase, on MDA production. Baseline MDA levels were similar in neonatal and adult hearts, were changed little by treatment with normoxic cardioplegia, and were elevated in both groups by treatment with hyperoxic cardioplegia. Thus, the degree of lipid peroxidation during ischemia is similar in neonatal and adult hearts. After 10 min of retrograde reperfusion subsequent to treatment with anoxic cardioplegia, the MDA content of adult hearts was significantly greater than that of similarly treated neonatal hearts. Addition of free radical scavengers to the reperfusion medium lowered the MDA content of adult hearts significantly, but not to the level of neonatal hearts. After 60 min of reperfusion subsequent to hyperoxic cardioplegia, adult hearts had higher MDA than neonates; addition of scavengers to the cardioplegia did not lower the MDA significantly in either group. Only 5 of 12 adult hearts recovered function after hyperoxic cardioplegia, while all 12 neonatal hearts recovered. Our results indicate that neonatal myocardium suffers less damage from oxygen centered free radicals during reperfusion than does adult myocardium. PMID- 1865674 TI - Depression of liver-specific gene expression in regenerating rat liver: a putative cause for liver dysfunction after hepatectomy. AB - We carried out studies on the expression of liver-specific genes during regeneration of the liver and searched for changes in the expression of oncogenes and housekeeping genes. Albumin and ornithine transcarbamylase genes were the liver-specific genes examined by Northern blot analysis, using total RNAs isolated from residual livers of Sprague-Dawley rats subjected to a 68% partial hepatectomy. The mRNA levels of both genes began to decrease 8 hr after hepatectomy, both reaching the lowest levels at 24 hr, and then recovered to some extent at 48 hr. In contrast, these levels in the housekeeping and growth-related genes were augmented during this period. This would suggest that there is a selective expression of growth-related and housekeeping genes, in preference to liver-specific genes during liver regeneration. The expression of these genes in the regenerating liver was simulated in primary cultured hepatocytes during the dedifferentiation processes. It would appear that the first step in regeneration of the residual liver is dedifferentiation, in which the depression of liver specific genes may be linked to liver dysfunction following hepatectomy. PMID- 1865675 TI - Metabolic and functional cardiac impairment after reperfusion with persantine. AB - The effect of dipyridamole (DYP) on postischemic myocardial function and metabolism was studied using the isolated rabbit heart model. Twenty-one isolated rabbit heart preparations were divided into two groups: KH (control N = 10) were reperfused after 24 min normothermic hyperkalemic arrest with modified Krebs Henseleit buffer (KH) while DYP (N = 11) were reperfused with KH and 5 X 10(-6) M DYP. Hearts were analyzed for myocardial function (DP, developed pressure, +dp/dt, -dp/dt) and metabolic function (ATP, CrP, ADP, AMP, purines, and lactate levels). Data analysis revealed significant reperfusion depression in DYP myocardial function compared with KH (P less than 0.05): DP (42 +/- 6 vs 89 +/- 7 mm Hg), +dp/dt (390 +/- 21.6 vs 1227 +/- 48.4), and -dp/dt (280 +/- 20.1 vs 677 +/- 19.8). Comparison of DYP to KH metabolic parameters was also significantly different (P less than 0.05): ATP (5.8 +/- 0.7 vs 9.5 +/- 1.4), ADP (2.1 +/- 0.2 vs 3.2 +/- 0.6), CrP (9.6 +/- 0.3 vs 17.2 +/- 1.3). Tissue purines (adenosine and inosine) were significantly elevated (P less than 0.01) in the DYP group, while coronary sinus purines and lactate loss were similar. Thus, the data suggest that DYP, present during postischemic reperfusion, depresses myocardial function by inhibiting adenosine phosphorylation, thereby decreasing the generation of high energy phosphates without increased substrate loss or ischemia. PMID- 1865676 TI - Immunosuppressive mechanism of 15-deoxyspergualin on sinusoidal lining cells in swine liver transplantation: suppression of MHC class II antigens and interleukin 1 production. AB - To elucidate the precise mechanism of action of 15-deoxyspergualin (DSG) in swine liver transplantation, the expression of MHC class II antigens (Ia) on hepatic sinusoidal lining cells (SLC) and their production of interleukin-1 (IL-1) were examined. In our previous study, we isolated sinusoidal endothelial cells (SEC) and Kupffer cells (KC) by enzymatic digestion and centrifugal elutriation, and demonstrated that both SEC and KC present alloantigens effectively and generated IL-1 in response to allogenic or lipopolysaccharide stimulation. Animals were divided into three groups: group 1, nontransplanted normal controls (n = 3); group 2, no immunosuppressive treatment following liver transplantation (n = 5); group 3, DSG (0.8 mg/kg/day) intravenously for 7 days following liver transplantation (n = 5). At 1 week after transplantation, the three liver grafts in groups 2 and 3 were processed for the study of Ia expression and IL-1 production on SEC and KC. The expression of Ia was detected in 21.5 +/- 4.7% of SEC and 24.3 +/- 11.1% of KC in group 1. In group 3, Ia expression was suppressed compared with group 2, being 3.6 +/- 2.8% versus 22.0 +/- 2.8% for SEC (P less than 0.02) and 15.5 +/- 11.3% versus 24.3 +/- 7.1% for KC. IL-1 production by SEC and KC was respectively 11,483 +/- 3311 cpm and 9077 +/- 2161 cpm in group 1. In group 3, IL-1 production was inhibited compared with that in group 2, being 7190 +/- 883 cpm versus 19,297 +/- 5182 cpm for SEC (P less than 0.05) and 16,130 +/- 3769 cpm versus 25,857 +/- 3963 cpm for KC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865677 TI - Cyclosporin A augments human platelet sensitivity to aggregating agents by increasing fibrinogen receptor availability. AB - Clinical use of cyclosporin A (CsA) has been associated with platelet hypersensitivity and an increased incidence of thrombotic and vasoactive events. The purpose of this study was (1) to confirm that CsA enhances platelet sensitivity to the soluble agonists, adenosine diphosphate (ADP) and epinephrine (EPI), and (2) to determine if this enhancement is mediated by alteration in the availability of platelet surface fibrinogen receptors, a final mediator of platelet activation. Mean log dose of ADP required to achieve complete second wave platelet aggregation in vitro decreased from 1.90 to 1.49 microM (n = 19, paired t test, P less than 0.05) and 2.86 to 2.11 microM (n = 16, P less than 0.05) following a 15-min and 3-hr incubation in the absence (saline) and presence of CsA (1000 ng/ml), respectively. At the threshold dose of ADP, concurrent thromboxane B2 levels at 15 min were 245 +/- 44 ng/ml (n = 12, saline) and 265 +/ 54 ng/ml (n = 9, CsA; P greater than 0.05). At 3 hr respective levels were 333 +/- 57 and 442 +/- 81 ng/ml (P greater than 0.05). Similar results were obtained with EPI. The number of fibrinogen binding sites in response to 50 microM ADP was determined in washed platelets in the absence and presence of CsA by radioligand binding. In 6 of 7 volunteers, CsA increased fibrinogen receptors from 26,635 +/- 4841 to 35,925 +/- 7290 sites/platelet (means +/- SEM; P less than 0.05). No change in receptor affinity was noted. In conclusion, cyclosporine does augment platelet reactivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865678 TI - Impact of exogenous growth hormone on host preservation and tumor cell-cycle distribution in a rat sarcoma model. AB - Growth hormone (hGH) has been reported to improve nitrogen balances and accrue lean mass tissue in stable subjects. However, the ability of hGH to positively influence host preservation in stressed catabolic states such as cancer-induced cachexia remains unproven. Thirty-seven sham or tumor implanted Fischer 344 rats were randomized to receive either 0.5 mg/kg/day hGH or saline (SAL) subcutaneously from Days 14 to 23 postimplantation. Plasma levels of hGh and somatomedin C/insulin-like growth factor I (IGF I) as well as IGF I bioactivity were determined at sacrifice. Gastrocnemius muscle protein content was used as a index of host lean tissue mass and the tumor response was evaluated via flow cytometry for analysis of cell-cycle distribution. Host cachexia was not attenuated by hGH as muscle protein content was similar in hGH and saline-treated groups. Despite elevated hGH levels (range, 77-222 ng/ml (GH) vs less than 2 ng/ml (SAL], IGF I levels and bioactivity were not elevated in GH-treated groups. In contrast, cancer-induced anorexia markedly decreased IGF I levels (4 U/ml vs 9 U/ml, NTB; P less than 0.01) and this response remained refractory to hGH administration. While final tumor weights were similar between GH- and SAL treated groups, hGH treatment caused a twofold increase in the proportion of aneuploid cells (P less than 0.05). In conclusion, hGH failed to attenuate lean mass dissolution in the tumor bearing host and this response may be related to the failure of IGF I induction. Conversely, the altered proportion of tumor aneuploid cells suggests a direct influence on tumor cell-cycling populations. PMID- 1865679 TI - Parasitic diseases reported in Memphis hospitals in 1984 and 1989. PMID- 1865680 TI - Pulsed dye laser therapy for port-wine stains in children. PMID- 1865681 TI - Pancreatic carcinoid with extensive osteolytic bone disease. PMID- 1865682 TI - Bronchial rupture. PMID- 1865683 TI - Postoperative fever, hypotension, and renal failure. PMID- 1865684 TI - Hemarthrosis and oral anticoagulants. PMID- 1865685 TI - Health risks from radon exposure. PMID- 1865686 TI - Stop, look, listen. PMID- 1865687 TI - A key to the most deadly lock. PMID- 1865688 TI - Counting the cost. PMID- 1865689 TI - Gripes, et. al. a lesson in loss prevention. PMID- 1865691 TI - A visit to the doctor. PMID- 1865690 TI - Loss prevention. PMID- 1865692 TI - The TMA Impaired Physician Peer Review Committee. A progress report. PMID- 1865693 TI - Pregnancy and childbearing in a population with biologic valvular prostheses. AB - Long-term performance of biological prostheses and course of pregnancy, labor, and delivery were evaluated in women less than 35 years of age. Between 1975 and 1987, 87 female patients received a porcine (n = 86) or pericardial valve (n = 1); the mean patient age was 26.8 years, with a range of 8 to 35 years. A total of 17 of these patients experienced 37 pregnancies. A total of 25 babies were delivered, of which 19 were babies of normal birth weight born at term and six were born prematurely (two of these were stillborn). There were six spontaneous abortions and five therapeutic abortions. The mean time from primary operation to first delivery was 29 months. Of the 17 pregnant patients, 14 were in normal sinus rhythm and three were in atrial fibrillation. One of those in fibrillation had a therapeutic abortion while receiving warfarin therapy, and another was successfully delivered of her neonate after 7 months of warfarin therapy. The remaining 15 patients were treated through 35 pregnancies without anticoagulants or antiplatelet agents. Of the total population of 87 patients, 32 (36.8%) were treated for valve-related complications. Structural valve deterioration occurred in eight patients (47.1%) of the pregnancy group and 10 patients (14.3%) of the nonpregnancy group (p less than 0.05). The freedom from structural valve deterioration at 10 years was 23.3% +/- 14% for the pregnancy group and 74.2% +/- 8.5% for the nonpregnancy group (p less than 0.05, age as a determinant, p not significant). There were eight valve-related deaths (1.5%/patient-year). Reoperation was performed in 59% of the pregnancy group and 19% of the nonpregnancy group, primarily for structural valve deterioration manifested as valvular obstruction from aggressive calcification (p less than 0.05). The freedom from reoperation at 10 years parallels freedom from structural valve deterioration (20.3% +/- 12.4% and 64.3 +/- 9.1% for the pregnancy and nonpregnancy groups, respectively, with p less than 0.05; with age added as a determinant, p not significant). The overall reoperative mortality was 8.7% (two patients). The biologic prostheses afforded successful pregnancy without fetal wastage or congenital anomalies and without significant maternal morbidity or mortality. PMID- 1865694 TI - Patterns of failure in Hancock pericardial bioprostheses. AB - A series of Hancock pericardial valve bioprostheses was reviewed for cases of primary valve failure. Thirteen mitral and 10 aortic valve explants were recovered from 21 adult patients. Mitral valves had been in place for a mean of 56.4 months, and aortic valves for 53.8 months. All valves failed with cusp tears from stents (with a mean of 1.7 for mitral valves and 2.6 for aortic valves) in a predictable pattern, suggesting that wear and stress at cusp stitch sites are important in their pathogenesis. The topography of these tears is illustrated as are the less common associates of primary failure, such as calcification, fibrosis, and thrombosis. Similarities and differences of this valve's failure compared with that of the Ionescu-Shiley pericardial valve are discussed. PMID- 1865695 TI - Bilateral enlargement of the aortic valve ring for valve replacement in children. New operative technique. AB - We report a new technique for the bilateral enlargement of a small aortic anulus in two children by the insertion of a bifurcated teardrop-shaped Dacron fabric lined with a porcine pericardium. Our experience in two children indicates that this technique will permit the insertion of a prosthetic valve that is four sizes larger than that measured with the native anulus intact in children weighing around 15 kg. It entails no risk of distorting the mitral valve, damaging the conduction system, the main coronary arteries or their important trunks, or of leading to left ventricular dysfunction. PMID- 1865696 TI - Monitoring of mononuclear cell subsets isolated from the coronary sinus and the right atrium in patients after heart allograft transplantation. AB - The rejection of a transplanted heart leads to an accumulation of mononuclear cells in the cardiac tissue and to reactions of the antigen-recognizing cells with the foreign tissue. Consequently, during rejections immunologic changes, such as the number of mononuclear cells and the patterns of mononuclear cell subpopulations, should be detectable by analysis of mononuclear cells from the coronary sinus of transplanted hearts. Seventy-nine endomyocardial biopsies were performed in 37 patients. Severity of graft rejection was classified by the Billingham scheme. Thirty-two biopsy specimens showed no rejection, 33 mild, and 14 moderate rejection. After endomyocardial biopsy the coronary sinus was catheterized under x-ray guidance. Heparinized blood samples were obtained from the coronary sinus and the right atrium, and mononuclear cell counts and subpopulation pattern were compared. Patients without rejection and patients with mild rejection showed no significant differences in the patterns of mononuclear cell subpopulation identified in right atrium blood. However, a significant (1.56 fold) increase of mononuclear cells was assessed in the CS blood (p less than 0.01). Moderate rejections showed a 4.2-fold augmentation of mononuclear cells in the coronary sinus (p less than 0.005) compared with nonrejections. In addition, the T-helper/inducer (CD4) percentage increased from 27.1% in the right atrium to 41.2% in the coronary sinus (p less than 0.005), natural killer cells (CD16) from 17.7% to 31.8% (p less than 0.005), and the interleukin 2 receptor-bearing cells from 6.6% to 15.3% (p less than 0.005). Percentage of pan-T cells (CD3), T cytotoxic/suppressor cells (CD8), and monocytes (CD14) showed no statistically significant changes. These findings correlated with grading according to endomyocardial biopsy. Using the ratio of values obtained from cells of the coronary sinus and the right atrium rendered the coronary sinus immunologic monitoring independent of changes in the administered immunosuppressive regimen. The specificity of the described method was as good as that of endomyocardial biopsy. It is concluded that the discrimination of the patterns of mononuclear cell subpopulations from right atrium versus coronary sinus blood samples is highly sensitive and allows the correct diagnosis of graft rejection within 1 to 2 hours. PMID- 1865697 TI - Two-day preservation of major organs with autoperfusion multiorgan preparation and hibernation induction trigger. A preliminary report. AB - A new autoperfusion multiorgan preparation was studied in which the heart and lungs were removed with the liver, pancreas, duodenum, and both kidneys en bloc while being perfused by the heart and oxygenated by the lungs. A respirator with 50% oxygen was used for ventilation. Fresh blood, glucose, electrolytes, mannitol, and antibiotics were given through the portal vein. Fifteen mongrel dogs were used. In the study group (seven dogs), 10 ml of plasma containing hibernation induction trigger, obtained from deeply hibernating woodchucks, was given intravenously 2 hours before the operation, and 4 ml was given every 4 hours during the preservation period. In the control group (eight dogs), no hibernation induction trigger was used. Survival time in the study group ranged from 33 to 56 hours (mean 43.4 +/- 4.1 hours), longer than that of the control group, which was 9 to 31 hours (mean 16.2 +/- 2.6 hours, p less than 0.001). In the study group aortic systolic pressure ranged from 64 +/- 5 to 92 +/- 7 mm Hg, arterial oxygen tension from 180 +/- 35 to 285 +/- 66 mm Hg. Urine output ranged from 15 to 70 ml/hour. Blood urea nitrogen declined from 15.6 +/- 2.5 to 6.6 +/- 1.3 mg/dl (p less than 0.01); creatinine declined from 0.8 +/- 0.03 to 0.3 +/- 0.01 mg/dl (p less than 0.01). Severe liver congestion and premature renal failure occurred in the control group but did not occur in the study group. In the study group one lung was transplanted after 33 hours of preservation with simultaneous contralateral pulmonary artery ligation. Good lung function was maintained after transplantation. Although the exact mechanism by which hibernation induction trigger extends tissue survival time is still not clear, its effect on organ preservation is profound. This study also produced one of the longest average survival times for organ preservation. PMID- 1865698 TI - Long-term preservation of the mammalian myocardium. Effect of storage medium and temperature on the vulnerability to tissue injury. AB - Human heart preservation for transplantation commonly involves infusion of cold cardioplegic solutions and subsequent immersion in the same solution. The objectives of the present study were (1) to establish the temporal relationship between storage time (at 10 degrees C) and the postischemic recovery of function in the isolated rat heart, (2) to assess, by metabolic and functional measurements, whether storing the heart in fluid as opposed to moist air had any effect on the viability of the preparation, and (3) to ascertain the optimal storage temperature. Isolated rat hearts (at least 6 in each group) were infused for 3 minutes with St. Thomas' Hospital cardioplegic solution No. 2 at 10 degrees C, stored at 10 degrees C for 6, 12, 18, or 24 hours, and then reperfused at 37 degrees C. Mechanical function, assessed by construction of pressure-volume curves (balloon volumes: 20, 40, 60, 80, 100, and 120 microliters), was measured before ischemia and storage and after 60 minutes of reperfusion. Function deteriorated in a time-dependent manner; thus at a balloon volume of 60 microliters the recovery of left ventricular developed pressure was 84.2% +/- 5.3% after 6 hours (p = not significant when compared with preischemic control); 69.1 +/- 3.3% after 12 hours (p less than 0.05); 55.6% +/- 4.4% after 18 hours (p less than 0.05), and 53.0% +/- 6.8% (p less than 0.05) after 24 hours of storage. Other indices of cardiac function, together with creatine kinase leakage and high energy phosphate content, supported these observations. Since the recovery of the left ventricular developed pressure balloon volume curves were essentially flat after 18 and 24 hours of storage, either 6 or 12 hours of storage were therefore used in subsequent studies. Comparison of storage environment (hearts either immersed in St. Thomas Hospital cardioplegic solution No. 2 or suspended in moist air at 10 degrees C for 6 or 12 hours) revealed no significant differences in functional recovery between the groups. Thus hearts recovered 94.9% +/- 3.5% and 113.7% +/- 12.4%, respectively, after 6 hours of storage and 71.6% +/- 2.4% and 54.2% +/- 7.9%, respectively, after 12 hours of storage. Enzyme leakage and tissue water gain were also similar in both groups of hearts. Finally, hearts (n = 6 per group) were subjected to 12 hours' storage at 1.0 degree, 5.0 degrees, 7.5 degrees, 10.0 degrees, 12.5 degrees, 15.0 degrees, and 20.0 degrees C.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1865699 TI - Long-term follow-up after prosthetic replacement of the superior vena cava combined with resection of mediastinal-pulmonary malignant tumors. AB - The contraindication to curative excision of mediastinal and pulmonary cancers because of invasion of the superior vena cava is now challenged by the existence of vascular prostheses that are suitable for venous replacement. Between 1979 and 1990 22 patients underwent resection of lung cancer (n = 6) or malignant mediastinal tumors (n = 16) involving the superior vena cava. Resection was done with concomitant venous reconstruction, and polytetrafluorethylene grafts were used. All bronchogenic carcinomas necessitated right pneumonectomy, whereas the excision of mediastinal tumors had to include pulmonary resections in nine patients (five lobectomies and four sublobar resections) and the right phrenic nerve in 12 patients. Venous reconstruction was performed by interposition of a large polytetrafluoroethylene graft between the proximal and cardiac ends of the superior vena cava (n = 8), or between one (n = 10) or both brachiocephalic veins (n = 4) and the right atrium. One patient died postoperatively (4.5%), and another had mediastinitis that was successfully treated by omentopexy. Chemotherapy was administered preoperatively to five patients and postoperatively to seven patients; radiotherapy was administered to two and 10 patients, respectively. The overall actuarial survival rate is 48% at 5 years, with 11 patients presently alive. The survival rate of patients with mediastinal tumors is 60% at 5 years. Among the patients with lung cancer, two with N1 disease are alive at 16 and 51 months, and one died at 38 months; the two patients with N2 disease died at 6 and 8 months. Only one graft occlusion occurred in the postoperative period; another occurred 14 months after operation and was precipitated by insertion of a central venous catheter. The patency of all remaining grafts was demonstrated after an average time of 23 (1 to 98) months. On the basis of these results, polytetrafluoroethylene graft replacement of the superior vena cava should be part of the planning and execution of radical excision with curative intent of mediastinal and right pulmonary malignant tumors that are not present with other contraindications, such as pleural or distant metastasis and severe systemic disease. PMID- 1865700 TI - Routine computed tomographic scans, selective mediastinoscopy, and other factors in evaluation of lung cancer. AB - Routine computed tomographic scan is advocated as the best noninvasive method of evaluating mediastinal nodes for cancer spread. Positive studies should be confirmed histologically. Large size, central location, unfavorable cell type, poor cellular differentiation of the primary cancer, and weight loss also correlate with increased likelihood of mediastinal involvement. PMID- 1865701 TI - Results of total cavopulmonary connection in the treatment of patients with a functional single ventricle. AB - Total cavopulmonary connection was proposed as a modification of the Fontan procedure that might have greater benefits than previous methods. To assess this procedure we reviewed case histories of 38 patients (aged 17 months to 30 years) who underwent Fontan procedures with cavopulmonary anastomoses between January 1987 and December 1989. The group included 32 patients with univentricular heart, 2 with pulmonary atresia and intact ventricular septum, 3 with tricuspid atresia, and 1 with hypoplastic left heart syndrome. One or more previous palliative procedures were performed in 34 patients, including 19 systemic-pulmonary shunts, 16 pulmonary artery bandings, 7 atrial septectomies/septostomies, 7 Glenn shunts, and 1 patent ductus arteriosus ligation. Preoperative hemodynamics showed a pulmonary artery pressure of 12 mm Hg (range 6 to 22 mm Hg), pulmonary-systemic flow ratio of 1.6 (range 0.37 to 3.0), left ventricular end-diastolic pressure 9 mm Hg (range 3 to 15 mm Hg), and systemic arterial oxygen saturation of 82% (range 67% to 94%). Concomitant with cavopulmonary connection, 13 patients underwent additional procedures, including 9 atrioventricular valve annuloplasties, 4 Damus-Stansel-Kaye procedures, and 2 resections of subaortic membranes. Modifying the Fontan procedure in this fashion was particularly useful in the management of 2 patients with pulmonary atresia and intact ventricular septum who had right ventricular-dependent coronary blood flow. Cavopulmonary anastomosis and atrial septectomy were performed in both patients, with resultant inflow of oxygenated blood to the right ventricle and coronary arteries. Excellent postoperative results were noted in each. Postextubation hemodynamics for the entire group included a mean right atrial pressure of 13 mm Hg (range 11 to 17 mm Hg), a mean left atrial pressure of 6 mm Hg (range 3 to 12 mm Hg), and a room air oxygen saturation of 96% (range 92% to 98%). Seven patients had pleural effusions, 3 required postoperative pacemaker placement, and 2 required reoperation for tamponade. A venous assist device was required in one patient on the second postoperative day, but the patient was weaned successfully within 24 hours. One early death (2.6%) occurred in a patient who had intractable ventricular fibrillation 2 days after operation. There was one late cardiac death (2.7%) caused by ventricular failure and one late noncardiac death. These results demonstrate that total cavopulmonary connection provides excellent early definitive treatment, with low morbidity and mortality, for a variety of complex congenital heart lesions. PMID- 1865702 TI - Surgical management of the conal (supracristal) ventricular septal defect. AB - Surgical management of the conal (supracristal) ventricular septal defect differs significantly from the management of the perimembranous (infracristal) ventricular septal defect. The absence of a portion of the conal septum can lead to prolapse of the right cusp of the aortic valve, which predisposes these patients to aortic insufficiency. Between January 1980 and December 1989, 36 children with conal ventricular septal defect underwent intracardiac repair. Diagnosis was by echocardiography, cardiac catheterization, and intraoperative exploration. Preoperative evaluation showed that 26 patients (72%) had aortic valve prolapse and 16 (44%) had aortic insufficiency. Pulmonary-to-systemic flow ratios ranged from 1:1 to 3.5:1 (mean 2.0:1.0). Ten patients (27%) were believed to have clinical congestive heart failure. Age at the time of operation ranged from 2 weeks to 18 years (mean 5.5 years). Operative exposure was through the pulmonary artery (26), aorta (4), right ventricle (3), or right atrium (3). Simultaneous aortic valve suspension for aortic insufficiency was performed in four patients. Operative survival was 100%. Follow-up is complete in all patients and ranges from 0.5 to 9 years (mean 4.3 years). All patients are in normal sinus rhythm. No residual ventricular septal defects have been identified. Twenty-three of 36 patients (64%) have no evidence of aortic insufficiency; 12 of 36 (33%) have trivial or mild aortic insufficiency. One patient with initial severe aortic insufficiency underwent repeat aortic valvuloplasty 3 years after ventricular septal defect closure and aortic valve suspension. No patients have required aortic valve replacement. Surgical management of the conal ventricular septal defect differs from that of the perimembranous ventricular septal defect in two critical aspects. The operative approach should be through the pulmonary artery. This allows the best exposure of the remaining conal septum and the pulmonary and aortic valve leaflets, facilitating closure of the defect without injury to the valves or conduction system. Conal ventricular septal defects should undergo early closure, regardless of shunt volume, to prevent progressive aortic insufficiency. PMID- 1865703 TI - Myocardial reperfusion injury. Platelet-activating factor stimulates polymorphonuclear leukocyte hydrogen peroxide production during myocardial reperfusion. AB - To study the roles of platelet-activating factor, polymorphonuclear leukocytes, and oxygen free radicals in myocardial reperfusion injury, we subjected 10 sheep to 90 minutes of mid-left anterior descending coronary artery followed by 6 hours of reperfusion. Stainings with gentian violet and tetratriphenyl ammonium chloride demonstrated 20% +/- 3% of the left ventricular mass at risk for ischemia, of which 75% +/- 10% underwent infarction. Coronary sinus blood was assayed for platelet-activating factor and neutrophil hydrogen peroxide production before and during coronary occlusion and during reperfusion. Platelet activating factor was isolated by column chromatography and lipid extraction and quantified by radioimmunoassay. Neutrophil hydrogen peroxide production was measured by a 2',7'-dichlorofluorescein flow-cytometric assay. Platelet activating factor was elevated to 899 +/- 210 pg/ml at 15 minutes of reperfusion, compared with the preocclusion level of 271 +/- 55 pg/ml and coronary occlusion level of 359 +/- 64 pg/ml (p less than 0.05; analysis of variance). Neutrophil hydrogen peroxide production, measured on a relative fluorescence scale, was also elevated to a level of 141 +/- 27 at 1 hour of reperfusion, compared with the preocclusion level of 103 +/- 6 and the coronary occlusion level of 114 +/- 13 (p less than 0.01; analysis of variance). Both of these parameters returned toward baselines at the end of 6 hours of reperfusion. Histologic examination revealed infiltration of polymorphonuclear leukocytes into the interstitium of the reperfused myocardium. Neutrophils isolated from unoperated and healthy sheep demonstrated a graded dose response in hydrogen peroxide production when stimulated by purified platelet-activating factor in vitro. These findings suggest that platelet-activating factor is released in the coronary circulation and is a mediator of oxygen free radical production in polymorphonuclear leukocytes during myocardial reperfusion. PMID- 1865704 TI - Invited letter concerning: neutrophil activation during cardiopulmonary bypass. PMID- 1865705 TI - Modification of De Vega tricuspid annuloplasty. PMID- 1865706 TI - Exit block in pediatric cardiac pacing. PMID- 1865707 TI - Coronary artery bypass graft in the elderly. PMID- 1865708 TI - Reply to invited letter concerning: neonatal aortic stenosis. The balloon deflated? (J Thorac Cardiovasc Surg 1990;100:927-89) PMID- 1865709 TI - Median sternotomy for high-risk patients with bilateral pulmonary disease: a case report. PMID- 1865710 TI - Wife abuse during pregnancy: a nursing research study. PMID- 1865711 TI - [Treatment of basalioma]. PMID- 1865712 TI - [Foreign models can help us to estimate the costs of health care services]. PMID- 1865713 TI - [Create a central unit to support abused children]. PMID- 1865714 TI - [Why increase the indications for Zovirax?]. PMID- 1865715 TI - [Free interpretations of facts on the HIV epidemic among drug addicts]. PMID- 1865716 TI - [Is vaccination against pregnancy a way to stop overpopulation in the world?]. PMID- 1865717 TI - [Clozapine treatment in schizophrenia. A safety system is needed to prevent side effects]. PMID- 1865718 TI - [Mutation diagnosis is a possibility for the half of the families with acute intermittent porphyria]. PMID- 1865719 TI - [Congenital heart defects among children are surveyed in a Swedish registry]. PMID- 1865720 TI - [It is possible to discover tendencies through registry studies: the most difficult injuries are strongly increasing according to the Patient Insurance Registry]. PMID- 1865721 TI - [Curettage and cryosurgery as a safe method for treatment of non-melanoma skin cancer of the nose and ear]. AB - Treatment of non-melanoma skin cancer of the nose and ear is often complicated. In the article is described combination treatment with thorough curettage and cryosurgery of 125 tumours, 98 of the nose and 27 of the ear, with no recurrence during a mean follow-up of 25 months. PMID- 1865722 TI - [Lobac caused a life-threatening burn-like skin injury]. PMID- 1865723 TI - [Guidelines on nursing ethics, more knowledge, increased consciousness as results of a project on ethics in a primary health care district]. PMID- 1865724 TI - [Compulsory isolation of HIV-positive persons--why is it so difficult to agree?]. PMID- 1865725 TI - [Antibiotics containing pivalic acid and carnitine deficiency. A report of the present status--therapeutic recommendations]. PMID- 1865726 TI - Laser midline glossectomy as a treatment for obstructive sleep apnea. AB - Multiple site specific procedures have been proposed to treat obstructive sleep apnea syndrome (OSAS). Midline glossectomy (MLG) is a procedure that directly enlarges the hypopharyngeal airspace using the carbon dioxide laser. The initial experience of 12 patients is presented. Midline glossectomy as the sole procedure was performed on 11 patients who had failed uvulopalatopharyngoplasty (UPPP) and who were felt to have significant hypopharyngeal collapse on physical examination and Muller's maneuver. One patient with primary hypopharyngeal narrowing underwent MLG. Five (42%) were considered responders with Respiratory Disturbance Index (RDI) decreasing from 60.6 per hour to 14.5 per hour. In seven nonresponders, there was no significant change in the RDI (62.6 events per hour to 48.4 events per hour). Cephalometric analysis showed that responders tended to be more retrognathic (sella-nasion-supramentale (S-N-B = 74.4 degrees)) than nonresponders (S-N-B = 79.3 degrees). Responders were significantly less obese (body mass index (BMI = 30.6)) than nonresponders (BMI = 37.9). There were five minor complications including minor bleeding (n = 3), prolonged odynophagia (n = 1), and minor change in taste (n = 1). There were no major complications, and no persistent difficulties with speech or swallowing. These results demonstrate that direct surgical modification of the tongue base and associated structures can significantly impact obstructive apnea. Midline glossectomy or similar procedures may be useful in a subset of patients with OSAS. PMID- 1865727 TI - Stapedectomy: long-term hearing results. AB - The initial improvement in hearing following stapedectomy usually deteriorates with the passage of time. We studied the long-term results of stapedectomies performed on 42 patients (49 ears) between 1959 and 1969 who had a minimum follow up of 18 years. Both air conduction (AC) and bone conduction (BC) thresholds progressively deteriorated over the long term. The degree of BC loss paralleled that expected from presbycusis alone. A greater deterioration was noted in the AC levels, producing a recurrent conductive hearing loss in the speech frequencies. Age at the time of surgery had no effect on the long-term outcome. Comparison of the average preoperative speech discrimination scores (SDS) to the 1-year postoperative SDS and the long-term SDS revealed a 1.1% and 16.7% drop, respectively. The improvement in the average speech reception threshold (SRT) obtained 1 year postoperatively deteriorated by less than 1 dB per year over the long term. Patients with a higher SDS (more than 95%) preoperatively fared better in the maintenance of speech discrimination than those with a lower SDS (less than 95%). The preoperative SRT level was predictive of the timing for the requirement of hearing amplification. The postoperative SRT level was predictive of the timing for the requirement of hearing amplification. The caused by presbycusis, combined with a recurrent conductive loss in the speech frequencies rather than cochlear otosclerosis. Although the decline in hearing following stapedectomy exceeds the rate of hearing loss due to presbycusis, many individuals, after successful stapes surgery, are able to delay the need for hearing amplification for longer periods than had been previously reported. PMID- 1865728 TI - Allergic fungal sinusitis: problems in diagnosis and treatment. AB - Although first described in 1983, allergic Aspergillus sinusitis (AAS) has yet to gain wide recognition among otolaryngologists and pathologists. We have treated three patients with a history of asthma, nasal polyposis, and recurrent pansinusitis who fit the description of allergic Aspergillus sinusitis. Histopathologically, mucinous material with abundant eosinophils and Charcot Leyden crystals ("allergic mucin") is interspersed with fungal hyphae. Immunologic characteristics include serum total immunoglobulin E (IgE) elevation, increased RAST classes, and cutaneous reactivity to molds. A retrospective analysis of the histopathology of 82 patients with chronic sinusitis was also undertaken. Eleven additional patients with classic allergic mucin were identified, but were found to be without evidence of fungal elements. The clinical features of all 14 patients are reviewed revealing the spectrum of disease. The difficulties of diagnosis and a therapeutic protocol which includes wide local debridement and postoperative use of systemic steroids are discussed. PMID- 1865729 TI - Ciprofloxacin: drug of choice in the treatment of malignant external otitis (MEO). AB - Ciprofloxacin, a fluorinated quinolone with high efficacy against Pseudomonas aeruginosa, was used in the treatment of 10 consecutive patients with malignant external otitis. All patients had skull base osteomyelitis documented by nuclear and computed tomography (CT) scans. Dosages of 1.5 g of ciprofloxacin daily were used for a mean average of 10 weeks. All patients were considered cured with a minimum follow-up of 18 months after completion of therapy. A new classification of malignant external otitis (MEO) is presented. PMID- 1865730 TI - A new approach to serial monitoring of ultra-high frequency hearing. AB - Early detection of drug-induced hearing loss is best accomplished by monitoring hearing at the ultra-high frequencies. Unfortunately, at these frequencies, sound pressure at the tympanic membrane (TM) critically depends on the placement of the sound source and on the size and shape of each individual external ear. Thus, presentation of the same sound may yield substantially different sound pressures in different ears. Moreover, only a slight change in the position of an earphone may yield large changes in sound pressure at the tympanic membrane. As a consequence of these characteristics, the reliability of ultra-high-frequency audiometry is poorer than at conventional audiometric frequencies. However, for the early detection of ototoxicity, it is necessary only to monitor for increases in thresholds. Accordingly, a sound-delivery system was developed which fixes the relative position of the sound source and the ear. This system ensures that sounds at the same level may be presented during different test sessions. To assess the stability of ultra-high-frequency thresholds, normal hearing subjects were tested in sessions separated by several weeks. Thresholds were obtained between 1 and 16 kHz and were found to be reliable. It is concluded that this type of system can be used for monitoring the ototoxic effects of drug therapy. PMID- 1865731 TI - Lightning and its effects on the auditory system. AB - Patients struck by lightning can present with a wide variety of unusual otologic problems including burns to the external auditory canal, tympanic membrane rupture, middle ear injury, and sensorineural hearing loss. Four patients who incurred various otologic problems, including one patient with previously unreported bilateral oval window fistulas following lightning injury, are presented. Audiologic, otologic, and surgical findings are reviewed as well as patient follow-up and outcome. PMID- 1865732 TI - Facial nerve trauma: optimal timing for repair. AB - Due to the uncertainty of optimal timing for facial nerve repair after severe trauma, a study was designed to investigate facial nerve repair in micro-pigs by grafting at intervals after nerve transection ranging from 0 to 90 days. Following adequate time for regeneration, it was possible to electrically stimulate across the nerve graft in all animals. No significant difference existed between operative groups for electrophysiologic testing. Axon counts demonstrated a trend toward a lower regeneration rate in more delayed grafts. This trend and the ease of grafting with less scar and nerve stump resection suggest that the best results may be obtained with grafting as early as possible. Grafting at 21 days, the peak of neuron cell-body metabolic activity, did not produce better results. Since statistically significant differences do not exist between individual groups, grafting several months after trauma can be successful, if medically necessary. PMID- 1865733 TI - The role of the posterior cricoarytenoid muscle in phonation: an electromyographic investigation in dogs. AB - The activity of the posterior cricoarytenoid muscle during respiration has been well investigated electromyographically. Its activity during phonation, however, has not been studied systematically. We, therefore, focused our attention on the phonatory activity of the posterior cricoarytenoid muscle to confirm whether it also contracts during phonation, as has been reported by some researchers. In our series of 12 adult dogs, the posterior cricoarytenoid was active in 11 dogs and inactive in one dog during phonation. Our present study also showed that the posterior cricoarytenoid activity was stronger for phonation than for inspiration in 6, stronger for inspiration than for phonation in 3, and the same for phonation and inspiration in 2 dogs. The results obtained from the present electromyographic evaluation demonstrated that the posterior cricoarytenoid is activated during phonation. The authors believe that the posterior cricoarytenoid muscle has phonatory function and that the phonatory effect of this muscle on the vocal cord may play an important role in precise glottis control. PMID- 1865734 TI - Singular neurectomy update. II. Review of 102 cases. AB - During the past 18 years, 102 singular neurectomies (SN) were performed on 95 patients with chronic cupulolithiasis of the posterior canal sense organ. Bilateral sequential singular neurectomies were performed in 7 patients and unilateral singular neurectomies in 88 patients. Ninety-nine (97%) of the 102 singular neurectomies completely eliminated the positional nystagmus and vertigo produced by the involved (undermost) ear in the Hallpike maneuver. Following three singular neurectomies (3%), there was improvement but incomplete relief from the positional nystagmus. A sensorineural hearing loss caused by the singular neurectomies occurred in four patients (4%). A thorough knowledge of the surgical and histologic anatomy of the round window niche and singular canal, together with the use of local anesthesia to allow monitoring of a vestibular response to singular neurectomy are essential for effectiveness and safety. PMID- 1865735 TI - The nasal septum in relation to the development of the nasomaxillary complex: a study in identical twins. AB - The influence of the nasal septum and respiration, evaluated by the total nasal resistance (TR) on the development of the nasomaxillary complex, was studied in 42 identical twins. An understanding of this influence is important for a determination of whether surgery involving the nose should be performed in children. Comparison within and between twins with different septal deformities indicated that the cartilaginous nasal septum influences the development of the nose and the anteroposterior dimensions of the maxilla. Anterior septal deformities resulted in underdeveloped cartilaginous noses and a shorter anteroposterior dimension for the maxilla. No relation was found with regard to posterior septal deformities, which may be considered as part of the development of the midface. Vertical dimensions of the face were related to TR. Increased values of TR were significantly related to a shorter maxillary height. This may not express a causal relationship but rather genetically determined shorter facial dimensions. PMID- 1865736 TI - Wide vertical hemipharyngolaryngectomy with immediate glottic and pharyngeal reconstruction using a radial forearm free flap: preliminary results. AB - We propose a new technique of wide vertical hemipharyngolaryngectomy which combines resection of laterally localized extended pharyngolaryngeal tumors with immediate microsurgical reconstruction using a radial forearm free flap, including the tendon of the palmaris longus. It eliminates the limitations of resections, which are usually performed to avoid closure difficulties of the resulting defect. In addition, the new technique avoids the use of tumor neighboring structures for closure, fulfilling the oncological principles of surgery performed in this region. Our preliminary results show good restored deglutition and phonation. Postoperative irradiation does not seem to affect these results. PMID- 1865737 TI - Otologic sequelae after pneumococcal meningitis: a survey of 164 consecutive cases with a follow-up of 94 survivors. AB - As part of a comprehensive study on sequelae after pneumococcal meningitis, 94 of 111 consecutive survivors were re-examined 4 to 16 years after discharge. Twenty three patients had otological sequelae after pneumococcal meningitis. In these patients, 17 had hearing losses, 7 had tinnitus, 9 had vertigo, 13 had vestibular areflexia, 4 had loss of smell, and 3 had loss of taste. Among the patients with hearing loss, 4 were bilaterally deaf, 6 were unilaterally deaf, and 2 had mild and 5 had slight hearing losses. From correlations with extensive data from the medical records, preadmission antibiotic treatment appeared to protect from acousticovestibular damage. Purulent otitis media and otosurgical intervention did not correlate to the fatality rate or the development of sequelae. Acute purulent otitis media appeared as a concomitant manifestation, rather than the focus of pneumococcal meningitis. PMID- 1865738 TI - Otoplasty: critical review of clinical results. AB - Although it is generally believed that otoplasty provides uniformly gratifying results, thorough patient follow-up reviews are quite rare. Otoplasty surgery performed on 119 ears was retrospectively reviewed to assess the results of our cartilage-sparing technique. This method of otoplasty relies on a conchal set back and suture transfixation technique to improve the antihelical contour. Auricular medialization averaged 10.3 mm. Over-correction is required, particularly in the superior pole, as loss of correction with healing was approximately 40% of the initial medialization. Revision surgery due to loss of correction was necessary for 6.6% of the ears initially operated on by the senior author. Patients who presented following cartilage-cutting procedures tended to have a higher rate of revision and persistent postoperative stigmata. Complications in general were few; however, mersilene suture extrusion occurred in 8% of ears. Only one of these required revision surgery for associated loss of correction. Despite these drawbacks, over 95% of patients achieved satisfactory results using cartilage-sparing otoplasty techniques. PMID- 1865739 TI - Facial reanimation after acoustic neuroma excision: the patient's perspective. AB - Facial reanimation after acoustic neuroma excision is currently accomplished using a variety of surgical techniques. A multi-institutional survey of patient perceptions of facial reanimation success was accomplished by mailing a questionnaire to 809 randomly selected members of the Acoustic Neuroma Association. Four hundred sixty patients who underwent 296 reanimation procedures responded. Facial to hypoglossal nerve anastomosis, tarsorrhaphy, and upper eyelid implants were most frequently performed. The patient's estimations of initial deficit, spontaneous recovery, and overall satisfaction with the reanimation procedures are discussed. PMID- 1865740 TI - The lymphocyte transformation test with type II collagen as a diagnostic tool of autoimmune sensorineural hearing loss. AB - Immunological disorders of the cellular type can be diagnosed by the lymphocyte transformation test (LTT). An autoimmune mechanism of certain cases of sensorineural hearing loss (SNHL) can be evaluated by using human inner ear tissue as an antigen. Recent studies have shown that type II collagen plays an important role, not only in some autoimmune mediated rheumatoid diseases, but also as an antigenic substrate of inner ear tissue in autoimmune sensorineural hearing loss. This paper deals with results of the lymphocyte transformation test using type II collagen as antigen in 68 patients with progressive sensorineural hearing loss (PSNHL) and 68 healthy volunteers. Thirty-four patients showed a strong stimulation in the lymphocyte transformation test, in contrast to only four volunteers in the control group, two of whom had a history of rheumatoid arthritis. PMID- 1865741 TI - Surgical treatment of chronic otitis media and Meniere's syndrome. AB - Meniere's symptom-complex in conjunction with chronic otitis media (COM) has occasionally been encountered in otologic practice. This study compares the effects of various surgical techniques on patients with COM and Meniere's syndrome, primarily on incapacitating vertigo. One group of patients with incapacitating vertigo received endolymphatic system drainage procedures, either endolymphatic sac surgery (83 patients) or cochleosacculotomy (12 patients) simultaneously with surgery for COM. Another group (14 patients) had surgery for COM only. A comparison of the results for vertigo control between the two approaches indicates a significant difference in success rate in favor of endolymphatic system drainage procedures (80% versus 20%). COM is regarded as one of the causes of endolymphatic hydrops (EH). The results of this study seem to indicate both 1. the likelihood of the cause-and-effect relationship between COM and EH, and 2. the effectiveness of endolymphatic shunting procedures on control of incapacitating vertigo, thus supporting the contentions of other authors with regard to pathogenesis and sac enhancement in patients with COM and Meniere's syndrome. PMID- 1865742 TI - P300 response to tones and speech sounds after cochlear implant: a case report. AB - P300 potentials evoked by tones and spoken words were recorded from a 20-year-old man with a House-3M single-channel cochlear implant. Three months after cochlear implantation, there was a slight appearance of P300 response to both pure-tone stimuli and spoken-word stimuli; 6 months later, clearly identifiable P300 response to both pure-tone stimuli and spoken-word stimuli were obtained. These results are consistent with an encoding improvement for re-establishment of information processing after auditory rehabilitation. PMID- 1865743 TI - A safe technique for frontal sinus osteoplastic flap. PMID- 1865744 TI - A method for the treatment of abductor spasmodic dysphonia with botulinum toxin injections: a preliminary report. AB - A preliminary technical report of the effective treatment of abductor spasmodic dysphonia with botulinum toxin is presented. Our technique attempts to place the toxin close to the posterior cricoarytenoid muscle to allow diffusion of the material to the PCA. Our pilot study demonstrates that botulinum toxin is an effective approach for reducing or eliminating the abductor glottal spasms during phonation and, thereby, providing functional speech communication. PMID- 1865745 TI - Meniere's disease. PMID- 1865746 TI - Nicotinic action of anatoxin-a on guinea pig ileum antagonized by thymopentin. AB - (+)-Anatoxin-a (ANTX) stimulated guinea pig ileum contraction with a potency similar to that of acetylcholine (ACh); the stimulation was blocked by tubocurarine, hexamethonium, or atropine. Although the contraction stimulated by ANTX was blocked by atropine, no specific inhibition of the binding of [3H]N methylscopolamine to ileum membranes was observed in the presence of ANTX. Furthermore, ANTX failed to stimulate the secretion of alpha-amylase from pancreatic acinar cells, a process that is activated by cholinergic agonists at the muscarinic receptors. When the ileum itself was stimulated by ACh, the contraction was not blocked by either hexamethonium or tubocurarine. Preincubation of the ileum with hemicholinium caused a 50% reduction in the ability of ANTX to stimulate contraction. Based upon these data, it was inferred that ANTX binds to postganglionic synaptic nicotinic receptors in the ileum, thus releasing endogenous ACh, which in turn causes ileum contraction by interacting with the postsynaptic muscarinic receptors. It was also observed that thymopentin (TP-5), a pentapeptide corresponding to positions 32-36 of thymopoietin, blocked the stimulation of ileum contraction by ANTX. PMID- 1865747 TI - The effects of race on norepinephrine clearance. AB - Eighteen normotensive and 19 unmedicated hypertensive black and white male subjects were studied twice, during a 10 meq sodium diet for 5 days and a 200 meq sodium diet for 4 days. The subjects received an infusion of 3H-norepinephrine (3H-NE) during both low and high sodium diets to measure NE clearance. Dietary sodium and blood pressure classification had no effect on 3H-NE clearance. Infusion of pressor doses of NE also failed to alter 3H-NE clearance. Both normotensive and hypertensive blacks had increased 3H-NE clearance rates (p less than .001). The increased rate of 3H-NE clearance among blacks was not affected by alterations in dietary sodium or by pressor doses of NE. Increased NE clearance by blacks may help explain observations that white hypertensives in the age range we studied (25-46 years) have elevated plasma NE levels, while blacks have normal NE levels. PMID- 1865748 TI - Diurnal variations of serum beta 2-microglobulin in multiple myeloma. AB - The chronobiological circadian behaviour in serum levels of beta 2-microglobulin has been investigated in three groups of subjects: (A) 6 healthy controls; (B) 6 patients with untreated multiple myeloma; (C) 6 patients with multiple myeloma in complete remission after polychemotherapy. From all subjects, under the same standard life conditions, venous blood samples were drawn at 4-hour intervals starting from midnight during the span of a whole day. Circulating serum beta 2 microglobulin levels were determined by RIA method. The time-related data were analyzed by chronograms and the "mean-group cosinor" method. A significant circadian rhythm for serum beta 2-microglobulin was detected in the control group, with a peak in the morning hours, and in untreated patients, with a peak in the afternoon hours. No significant rhythm was found in treated patients with multiple myeloma. A significant mesor reduction was noted in patients with complete remission, correlated with the absence of circadian rhythm, in respect to untreated patients. These data suggest that serum levels of beta 2 microglobulin could be related to the neoplastic plasma cell proliferation and to the effect of therapy, and that the circadian evaluation could be used as a guide in monitoring myeloma patients. PMID- 1865749 TI - Metabolic effects of cyanate on mice at sea level and in chronic hypobaric hypoxia. AB - In order to evaluate the toxic effects of Sodium Cyanate (NaOCN), it was orally administered to growing mice at sea level (SL-CN) and to mice chronically exposed to intermittent hypobaric hypoxia (IHH-CN). The effects on body weight, in-vivo O2 consumption (VO2) and the respiratory function of liver mitochondria were evaluated. At sea level, the animals on cyanate lost weight in contrast with the controls that gained weight. When exposed to IHH, the controls lost weight and the animals on cyanate regained weight. After 2 months observation the weights of the IHH-CN and IHH-C were similar. The VO2 after one month of treatment was similar in the SL-C and in the SL-CN but it was lower in the IHH-CN when compared with IHH-C. The substrate-stimulated respiration of isolated liver mitochondria (ST4) was not affected by NaOCN, but the ADP-stimulated respiration (ST3) was reduced. The ratio ST3/ST4 (RCR) was also lower. These changes were present in both SL and in IHH and were much larger after three months of treatment. The toxic effects of chronic administration of NaOCN are discussed. PMID- 1865750 TI - Low pH medium induces calcium dependent release of CGRP from sensory nerves of guinea-pig dural venous sinuses. AB - Low pH medium has been shown to activate the 'efferent' function of capsaicin sensitive primary sensory neurons. Calcitonin gene-related peptide (CGRP) is released from capsaicin-sensitive afferents of guinea-pig superior sagittal and transverse sinuses (SSTS), by capsaicin or bradykinin. Here, we report that low pH medium produces a remarkable release of CGRP from SSTS, which was dependent on the concentration of hydrogen ions of the medium (pH 7-5). Moreover, the pH 5 evoked release of CGRP-LI was markedly reduced (by about 70%) in a calcium-free medium containing 1 mM EDTA or abolished in samples pre-exposed to 10 microM capsaicin. The present observation that lowering of the pH promotes release of a powerful vasoactive peptide from perivascular capsaicin-sensitive sensory nerves may have some relevance in the pathophysiology of brain injury and migraine headaches. PMID- 1865751 TI - Long term effects of prenatal cocaine exposure on bone in rats. AB - Prenatal exposure to cocaine has been shown to produce a variety of effects on skeletal development and mineralization in humans, mice, and rats. The effects of cocaine on bone cell function and mineral metabolism pre- and postnatally are poorly understood. The present study examined the long term effects of prenatal cocaine exposure on femoral growth and mineralization in male rats. Pregnant rats were given 80 or 100 mg cocaine hydrochloride/kg during days 7-20 of gestation. At birth, body weights of pups born to these females were significantly decreased compared to normal and pair-fed controls. At the termination of the study (32 weeks), body weights of offspring from C100-treated females were still lower than normal. Long term effects of prenatal exposure to cocaine on femoral growth were most pronounced in offspring of C80-treated females. Femur dry weight, ash weight, organic matrix weight and density were significantly reduced in these animals compared to normal or pair-fed controls. The apparent osteopenic effects of prenatal exposure to cocaine suggests some long term postnatal impact on bone cell or mineral metabolism. Previous studies of cocaine use during pregnancy in humans and animals have focused primarily on physical and behavioral defects in offspring. The present findings indicate that prenatal exposure to cocaine may also have long term consequences to the skeleton. PMID- 1865752 TI - Diazepam administered prior to coronary artery occlusion increases latency to ventricular fibrillation. AB - Few studies have addressed the antiarrhythmic potential of pretreatment with diazepam in acute myocardial infarction. Thus, the effect of diazepam pretreatment prior to coronary artery occlusion was examined in conscious pigs. Animals were instrumented with aortic catheters to measure arterial pressure, a pulmonary artery catheter for drug administration, and a snare around the left anterior descending coronary artery for permanent occlusion one week later. Diazepam (1 mg/kg iv bolus) or vehicle was administered 10 minutes prior to occlusion. Eight of 14 animals receiving diazepam (57%) and 13 of 22 receiving vehicle animals (59%) developed ventricular fibrillation following coronary occlusion. However, the latency to ventricular fibrillation was significantly shorter (7 +/- 1 min) in animals receiving vehicle compared to animals receiving diazepam (11 +/- 1 min). Significant increases in heart rate were seen up to 5 hours after coronary occlusion only in animals receiving vehicle. The results indicate that diazepam pretreatment can increase ventricular fibrillation latency and prevent heart rate increases following acute myocardial infarction. PMID- 1865753 TI - D1 agonist SKF 38393 antagonizes pentobarbital-induced narcosis and depression of hippocampal and cortical cholinergic activity in rats. AB - SKF 38393 (5 mg/kg), but not quinpirole, shortened the duration of loss of righting reflex produced in pentobarbital-narcotized rats. This effect was blocked by atropine (2 mg/kg), but not by atropine methylbromide, suggesting involvement of central cholinergic mechanisms. The analeptic effect was also blocked by SCH 23390 (0.2 mg/kg) or raclopride (2 mg/kg). SKF 38393 also increased sodium dependent high affinity choline uptake (HACU) in cortical and hippocampal synaptosomes that had been depressed by pentobarbital. SCH 23390 or raclopride prevented the SKF 38393 reversal of the depressed HACU, indicating that both D1 and D2 mechanisms were involved mediating the analeptic effect. These results provide neurochemical evidence that cortical and hippocampal D1 mediated cholinergic activation results in a behavioral arousal (analeptic) response. They also suggest that DA mechanisms may be involved in regulation of cortical and hippocampal cholinergic neurons. PMID- 1865754 TI - Human serum stimulates endothelin-1 synthesis more potently than prostacyclin production by cultured vascular endothelial cells. AB - Human serum stimulated the synthesis of a vasoconstrictive peptide, endothelin-1 (ET-1), and a vasodilatory prostanoid, prostacyclin (PGI2), by cultured human umbilical vein endothelial cells in a concentration- and time-dependent manner. Incubation in 20% concentration of the serum for 24 h stimulated ET-1 synthesis almost six-fold while PGI2 production increased two-fold. In addition, a tumor promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), inhibited the serum-induced ET-1 production and stimulated PGI2 synthesis in a concentration- and time-dependent manner. Our results suggest that human serum derived factor(s) stimulate the production of vasoconstrictive ET-1 more potently than the synthesis of vasodilatory PGI2 by human vascular endothelial cells and that the production of these agents is differentially regulated by PMA. PMID- 1865755 TI - Urinary excretion of digoxin-like immunoreactive factor and arginine-vasopressin in rats after several osmotic loads. AB - Urinary digoxin-like immunoreactive factor (DLIF), arginine-vasopressin (AVP) and other urinary parameters were investigated under normal conditions and after the i.p. injection of the following solutions: distilled water, isotonic and hypertonic NaCl, NaHCO3, KCl and urea, at a rate of 3 ml/100 g body weight. The measurement of digoxin-like immunoreactivity by two different radioimmunoassays showed that DLIF was stimulated by all volume loads regardless of the presence or absence of osmolar compounds. This dissociation between DLIF and urinary sodium excretion suggests that DLIF may not constitute the natriuretic hormone. Moreover, a dissociation between DLIF and AVP excretion also were found, which speaks against the hypothesis of a common mechanism of stimulation for both substances. PMID- 1865756 TI - Assay of circulating hyaluronic acid in the rat: study of diurnal variation and effect of anesthesia. AB - Serum hyaluronic acid (HA) may provide a good marker for the severity of joint disease in the rat since a positive correlation was observed in experimental models of arthritis. However, little is known about its physiological variation in rats. In the present work, we do not find any circadian rhythm of HA in healthy Sprague-Dawley rats in contrast to that observed in humans, whose serum levels vary during daytime. Furthermore, the influence of blood sampling conditions on HA concentrations was evaluated in conscious animals and by using different anesthetics. The greater reproducibility for the assay of HA is observed with the intracardiac puncture under ether inhalation. Blood sample collection in the absence of anesthesia leads to a significant increase in serum levels of HA, which could be attributed partly to enhanced joint movements generated by psychological stress. PMID- 1865757 TI - Incorporation of xenobiotic carboxylic acids into lipids. AB - Over thirty-six different xenobiotic carboxylic acids have been reported to form xenobiotic lipids. The majority form triacylglycerol analogs or cholesterol esters with fewer reports of polar lipids being formed. As yet there is insufficient information to deduce a relationship between the structure of the xenobiotic acid and its activity as a substrate for lipid biosynthesis, although the ability to form a CoA ester appears to be important. The action of monoacylglycerol acyltransferase, diacylglycerol acyltransferase, lecithin cholesterol acyltransferase and a carboxylesterase in synthesizing xenobiotic lipids has been demonstrated. One xenobiotic lipid has been shown to be the cause of granulomatous changes and there are some indications that others may prove to be of toxicological or pharmacological significance. Detailed investigations into several aspects of xenobiotic lipid biochemistry are still required. PMID- 1865758 TI - 1,25 (OH)2 vitamin D3-induced 45CA uptake in vascular myocytes cultured from spontaneously hypertensive and normotensive rats. AB - The effect of 1,25 (OH)2 vitamin D3 on basal 45Ca uptake was examined in vascular smooth muscle cells cultured from mesenteric arteries of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) normotensive rats. Basal uptake of 45Ca was significantly greater in myocytes of WKY than SHR at 5, 10, 30 and 60 min incubation with the isotope. Incubation with 1 ng/ml 1,25 (OH)2 vitamin D3 for 48 hr increased basal 45Ca uptake between 1-10 min in SHR and between 5-10 min in WKY. The dose-response relationship indicated that cells from both strains are equally sensitive to the calciotropic effects of 1,25 (OH)2 vitamin D3 with half maximal stimulation occurring at approximately 0.3-0.4 ng/ml. In cells of both strains maximal stimulation of 45Ca uptake was achieved only after a 12-24 hr period of incubation with hormone and pretreatment with cycloheximide inhibited 1,25 (OH)2 vitamin D3-enhanced 45Ca uptake. Although 45Ca binding by extracellular matrix material was significantly greater in WKY than SHR, 1,25 (OH)2 vitamin D3 had no effect on the amount of matrix 45Ca binding in either strain. These results suggest that 1,25 (OH)2 vitamin D3 induces an increase in intracellular protein synthesis that results in enhanced 45Ca uptake. The similar responses of the two strains indicate that hypertensive smooth muscle is not more sensitive to 1,25 (OH)2 vitamin D3 and the Ca2+ response is a general property of vascular muscle. PMID- 1865759 TI - Serum interleukin-6 in schizophrenic patients. AB - We examined serum interleukin-6 (IL-6) in 90 schizophrenic patients in remission and 90 normal controls using enzyme-linked immuno-sorbent assay (ELISA). We found a significant difference in variation between the schizophrenic and the control groups (F = 10.9, P less than .002). The difference in distribution was also statistically significant by Kolmogorov-Smirnov (chi-square = 45.0, P less than .001). Eight patients had aberrantly high serum levels of interleukin-6. Since the higher levels of IL-6 are characteristically found in several autoimmune disorders, our finding suggests a link between schizophrenia and immune response, which could be either autoimmune or a process induced by reactivation of viruses. PMID- 1865760 TI - Chronic prenatal nicotine exposure sensitizes rat brain to acute postnatal nicotine challenge as assessed with ornithine decarboxylase. AB - Prenatal exposure to nicotine has been shown to produce postnatal up-regulation of central nervous system nicotinic receptors and to alter subsequent differentiation of neural tissues. In the current study, pregnant rats received nicotine infusions of 6 mg/kg/day throughout gestation, administered by osmotic minipump implants; the postnatal development of cholinergic receptor reactivity was examined through measurements of the ability of acute nicotine administration to stimulate midbrain + brainstem ornithine decarboxylase (ODC) activity, a key regulatory enzyme in neural cell differentiation and growth. In control rats, the ODC response to nicotine was absent at birth and developed during the second postnatal week in parallel with the known ontogenetic rise of nicotinic receptors. Offspring of the nicotine-infused dams exhibited hyper-reactivity of ODC to postnatal acute nicotine challenge: the response developed earlier than in controls and subsequently the magnitude of the effect was 2-3 times greater. Since the development of cholinergic transmission influences differentiation of target cells, alterations in cholinergic nicotinic receptor mediated responses likely explain the delayed appearance of abnormal cell differentiation associated with prenatal nicotine. PMID- 1865761 TI - Stress modulates calcium mobilization in immune cells. AB - Both acute and chronic restraint stress modulated mitogen-induced increases in cytoplasmic free-calcium concentrations ([Ca2+]i) in mouse spleen cells. Dual color analysis of lymphocyte subpopulations demonstrated that acute (2 hour) restraint stress suppressed mitogen-stimulated increases in [Ca2+]i in CD4+ T cells, but enhanced [Ca2+]i in CD8+ T cells. Chronic restraint stress (2 hours daily for up to 21 days) resulted in a significant suppression of mitogen stimulated increases in [Ca2+]i in CD4+ T cells at 3 and 7 days, but not at 21 days. CD8+ T cells were unaffected by chronic stress. Chronic stress (for 7 days) had a modest suppressive effect on mitogen-induced Ca2+ responses in B cells. Within T lymphocyte subpopulations, both acute and chronic stress predominantly affected CD4+ T cells, which may induce a functional reversal of the CD4/CD8 ratios in vivo. Such a reversal could result in suppression of a variety of immune responses such as lymphocyte proliferation and antigen-specific antibody production. These findings indicate that the inhibitory effects of stress on calcium mobilization in lymphocytes may be an early event mediating stress induced immunosuppression. PMID- 1865762 TI - Rat liver outer mitochondrial carnitine palmitoyltransferase activity towards long-chain polyunsaturated fatty acids and their CoA esters. AB - The activity of the overt form of rat liver mitochondrial carnitine palmitoyltransferase or CPT0 (EC 2.3.1.21) towards different fatty acid substrates was studied. The following non-esterified fatty acids (NEFA) and their CoA esters in the presence of 1% bovine serum albumin (BSA) were tested: 16:0, 18:0, 18:1, 18:2, 18:3 omega 3, 20:4, 20:5 omega 3 and 22:6 omega 3. The data fit a square hyperbolic model for enzyme catalysis (p less than 0.001, non-linear regression). Asymptotic Vmax and K0.5, substrate concentration at one-half Vmax, were calculated using total concentrations of acyl-CoA, or unbound concentrations of NEFA. BSA was found to act as a true substrate reservoir for NEFA in that the dissociation of the NEFA-BSA complex was 10-330 times faster than the CPT0 reaction. Regardless of form (NEFA or CoA ester), 18:3 omega 3 gave the highest, while 22:6 omega 3 and 18:0 gave the lowest rates of acylcarnitine synthesis. Except for 18:3 omega 3 and 18:2, Vmax for NEFA was generally lower than for acyl CoA, with the greatest differences observed for 20:4, 20:5 omega 3 and 22:6 omega 3, suggesting that acyl-CoA synthesis may also be important in the control of the entry of these fatty acids into the mitochondria. The data provide an enzymatic rationale for the relatively low content of 18:3 omega 3 in esterified lipid. PMID- 1865763 TI - Thermal adaptation in biological membranes: functional significance of changes in phospholipid molecular species composition. AB - Quantities of 1-palmitoyl 2-docosahexaenoyl phosphatidylcholine (16:0/22:6-PC or PDPC) increase from 24 to 40 weight percent as a consequence of cold acclimation in mitochondrial membranes of rainbow trout liver (J. Comp. Physiol. 156, 665 674, 1986). The present study was undertaken to assess the impact of such a large change in the proportions of a single molecular species on the fluidity, lateral packing (as sensed by phospholipase A2), and permeability of biological membranes. These properties were examined in multilamellar liposomes prepared from binary mixtures of dipalmitoyl phosphatidylcholine (DPPC) and PDPC in proportions increasing from 10 to 40 mole% PDPC. Glucose permeability was positively correlated with both assay temperature and PDPC content. The temperature dependence of Na+ permeability declined steadily as the mole fraction of PDPC increased; consequently, sodium permeability was positively correlated with PDPC content at 5 degrees C, but inversely correlated at 20 degrees C. Phospholipase A2 activity was independent of both assay temperature and vesicle composition. Vesicles of all compositions displayed a single transition in the temperature dependence of 1,6 diphenyl-1,3,5-hexatriene (DPH) fluorescence polarization, which shifted to lower temperature and broadened as proportions of PDPC increased. At temperatures below the transition, fluidity was positively correlated with the mole fraction of PDPC, but interfacial and deeper regions of the bilayer were affected differently by variations in PDPC content. Nonelectrolyte permeability was the only index of membrane structure or function to be significantly correlated with the fluidity of the bilayer interior. The tendencies of PDPC to both fluidize the membrane and to reduce the temperature sensitivity of electrolyte permeation may promote the adaptation of membrane function to low temperature. PMID- 1865764 TI - Hydrolysis of neutral lipid substrates by rat hepatic lipase. AB - Rat hepatic lipase, an enzyme whose involvement in the catabolism of lipoproteins remains poorly defined, has both neutral lipid and phospholipid hydrolyzing activity. We determined the substrate specificity of hepatic lipase for 1-oleoyl sn-glycerol, 1,2-dioleoyl-sn-glycerol, and 1,3-dioleoyl-sn-glycerol in the Triton X-100 mixed micellar state, and compared these results to those obtained previously in our laboratory for the phospholipid substrates phosphatidic acid (PA), phosphatidylethanolamine (PE), and phosphatidylcholine (PC). Vmax values were determined by diluting the substrate concentration in the surface of the micelle by Triton X-100. The Vmax values obtained were 144 mumol/min/mg for 1 oleoyl-sn-glycerol, 163 mumol/min/mg for 1,2-dioleoyl-sn-glycerol, and 145 mumol/min/mg for 1,3-dioleoyl-sn-glycerol. These values were higher than those obtained earlier for phospholipids which were 67 mumol/min/mg for PA, 50 mumol/min/mg for PE and 4 mumol/min/mg for PC. In addition, the mole fraction of lipid substrate at half maximal velocity (K) in the surface dilution plot was lower for the neutral lipid substrates as compared to those obtained for the phospholipid substrates. When the hydrolysis of 1,3-dioleoyl-sn-glycerol mixed micelles was studied as a function of time, cleavage at the sn-1 and sn-3 positions occurred at the same rate, suggesting that hepatic lipase is not stereoselective with respect to 1,3-diacyl-sn-glycerol substrates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865766 TI - Reactions of dinitrogen pentoxide and nitrogen dioxide with 1-palmitoyl-2-oleoyl sn-glycero-3-phosphocholine. AB - The reactions of gaseous dinitrogen pentoxide (N2O5) and nitrogen dioxide (NO2) with 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC) coated on the inside surface of a glass reaction cell were studied at 298 K. Unsaturated phosphatidylcholines are significant components of pulmonary surfactant in the alveolar region of the lung and hence serve as a simple model to examine reactions of pulmonary surfactant with these oxidant air pollutants. Using high performance liquid chromatography (HPLC), Fourier transform infrared and fast atom bombardment mass spectroscopy, the major products of reactions of POPC with N2O5 and NO2 were separated and identified. In the POPC-N2O5 reaction using either air or helium as a buffer gas, the nitronitrate, vinyl nitro and allylic nitro derivatives, as well as a small amount of the trans-isomer of the starting material, were obtained. The nature of the products obtained from the POPC-NO2 reaction depends on the concentration of NO2 as well as whether air is present. At low NO2 concentrations (PNO2/N2O4 less than or equal to 3.8 Torr) in air or in helium, the trans-isomer of POPC was formed almost exclusively. At higher NO2 concentrations (PNO2/N2O4 greater than or equal to 20 Torr) in helium, the dinitro, vinyl nitro and nitro alcohol derivatives were formed. In the presence of air (or 24% 18O2 in helium), a nitronitrate and a dinitronitrate were additional products. Mechanisms for the formation of the observed products and implications for the inhalation of oxides of nitrogen are discussed. PMID- 1865765 TI - Lipoprotein lipase in rats fed fish oil: apparent relationship to plasma insulin levels. AB - To investigate the role of lipoprotein lipase (LPL) and hepatic lipase in the triacylglycerol lowering effects of fish oil, rats were fed lard (L), corn oil (CO) or menhaden oil (MO) as the primary fat source in otherwise identical diets. After 2 weeks, soleus muscle LPL differed between groups (MO greater than CO greater than L). Hepatic lipase did not differ between CO- and MO-fed rats but was elevated in L-fed rats. Adipose LPL did not differ between diet groups. Total epididymal fat weight was reduced in MO-fed rats. There was a significant positive correlation between adipose tissue weight and plasma free fatty acids. MO-fed rats had lower plasma insulin levels. Insulin was directly correlated with plasma triacylglycerol and glucose, consistent with a hyperinsulinemic, insulin resistant state in CO- and L-fed rats, and a protective effect with MO feeding. In addition, insulin was directly correlated with adipose LPL. A negative relationship between soleus muscle LPL and insulin approached significance. Soleus muscle LPL was significantly inversely correlated with triacylglycerol. The data indicate that increased skeletal muscle LPL, in response to MO or a MO induced decrease in insulin, may contribute to the triacylglycerol-lowering effects of fish oil. Decreased fat weight and adipose LPL and increased soleus muscle LPL and decreased plasma triacylglycerol suggest a shift from fat deposition to oxidation with MO feeding. The lack of response of hepatic lipase to MO feeding suggests that this enzyme does not contribute to the fish oil stimulated lowering of plasma triacylglycerol via hepatic reuptake of very low density lipoproteins or other triacylglycerol-rich lipoproteins. PMID- 1865767 TI - Determination of phospholipase D-mediated hydrolysis of phosphatidylethanolamine. AB - While phospholipase D-mediated hydrolysis of phosphatidylcholine is well documented, we have recently shown that phospholipase D-mediated hydrolysis of phosphatidylethanolamine (PtdEtn) [Kiss, Z., and Anderson, W.B., J. Biol. Chem. 264, 1483-1487 (1989); J. Biol. Chem. 265, 7345-7350 (1990)] is equally prominent. This made it necessary to define in detail the conditions required for the detection of agonist-stimulated PtdEtn hydrolysis. Using the [14C]ethanolamine-prelabeled rat-1 fibroblast model and 12-O-tetradecanoylphorbol 13-acetate (TPA) as a model compound with the known ability to stimulate phospholipase D, we demonstrated that optimal detection of TPA-induced ethanolamine release requires i) fractionation of water-soluble ethanolamine products; ii) addition of unlabeled ethanolamine to quench the phosphorylation of newly formed [14C]ethanolamine; and/or iii) prolonged preincubation of prelabeled cells in an isotope-free medium before the addition of TPA. This preincubation step reduced the cellular content of unincorporated 14C-labeled ethanolamine metabolites and improves the signal-to-noise ratio. PMID- 1865768 TI - Two novel phospholipid fatty acids from the Caribbean sponge Geodia gibberosa. AB - The novel fatty acids (Z)-6-nonadecenoic acid (1) and (Z)-17-pentacosenoic acid (2) were characterized in the sponge Geodia gibberosa. These fatty acids were mainly found in phosphatidylethanolamine and phosphatidylcholine. PMID- 1865769 TI - Psychiatric expert testimony: are the criticisms justified? (Part 1). AB - What weight is given psychiatric testimony when it is allowed in evidence? How much influence has the psychiatrist over the court process? These questions are examined in detail. PMID- 1865770 TI - The so-called 'therapeutic privilege' or 'contra-indication': its nature and role in non-disclosure cases. AB - This article critically examines the nature, scope and application of the so called 'therapeutic privilege' or 'contra-indication' as a defence to a failure to procure an informed consent to medical interventions. This is done within the context of the doctor's legal-ethical duty to inform his patient of the diagnosis and treatment on the hand and his sometimes conflicting medico-ethical duty to heal on the other, with special reference to the application of the defence in cases of solicited information and lie-telling. PMID- 1865771 TI - The breaching of medical confidentiality by reason of an order of court. AB - The ethical rule of medical confidentiality is not sacrosanct, for a doctor may be ordered by a court of law to make disclosures against his patients wishes. While this may assist in justice being done, it also raises the question of whether sufficient regard is paid to a patient's right to privacy. PMID- 1865772 TI - The impact of genetics on society: the law's response. AB - Technology has provided man with the ability to manipulate the genetic structure of the human race. The knowledge which geneticists have gained and will gain in future will raise numerous legal and ethical problems which will have to be debated and resolved within the parameters of the prevailing boni mores. PMID- 1865773 TI - On patient's rights. AB - A committee appointed by the World Health Organization was given the task of formulating a Declaration on the Rights of Patients. A member of this committee outlines the main guidelines formulated in the Declaration and discusses its utility in the struggle for patients' rights in general. PMID- 1865774 TI - AIDS: a right to be informed. AB - Individuals have to assume some responsibility for their own health. Governments do, however, have a duty to ensure that their citizens are armed with the necessary information and education. At present there appears to be a serious degree of ignorance about sexually transmitted disease in general and AIDS in particular. The importance of disseminating information on this topic is discussed. PMID- 1865775 TI - Alcohol on the television and in viewers' experience. AB - This study explores television viewers' perceptions of the portrayal of alcohol use in prime-time television programmes, and viewers' attitude toward alcohol use in real life. The actual incidence of the portrayal of alcohol use on television during the same period of the survey was also taken into consideration. These perceptions and attitudes were scrutinized for factors of risk in terms of the development of alcohol-related problems in South Africa with a view to assisting preventive agents in devising rational and timeous preventive programmes. PMID- 1865776 TI - Signal detectability: the use of ROC curves and their analyses. AB - Issues related to ROC curves are addressed. The original article on the subject by Lee Lusted, describing the "state of the art" 20 years ago, is reviewed. The concepts that Lusted addressed are then expanded, suggesting the current state of the art. New issues that have arisen with regard to ROC curves and their use in medicine are addressed. Finally, potential areas for future investigation are suggested. PMID- 1865777 TI - Bayesian reasoning in medicine: the contributions of Lee B. Lusted, MD. AB - The role of Bayesian reasoning in medicine is explored from the perspective of the writings of Dr. Lee B. Lusted. Starting with the influential article by Ledley and Lusted published in Science in 1959, the contributions of Dr. Lusted and his coauthors to medical education and clinical medicine are chronicled. An explication of Bayes' theorem and its reliance on the conditional independence assumption is followed by a summary of some applications to the interpretation of diagnostic tests. Opportunities for and challenges to the widespread application of Bayesian reasoning in daily clinical medicine are described. PMID- 1865778 TI - Decision-making studies in patient management: twenty years later. AB - This article surveys the contribution of decision analysis to diagnosis and treatment in medicine, beginning with a review of Dr. Lee B. Lusted's 1971 paper, "Decision-making studies in patient management." From this beginning methods of decision analysis were developed that were particularly appropriate to medical problems. The author reviews the effects of Dr. Lusted's interests in the field on subsequent research and publications, and critiques prophetic statements found in the early paper. PMID- 1865779 TI - A citation analysis of the work of Lee B. Lusted, MD. PMID- 1865780 TI - The impact of a rapid screen for streptococcal pharyngitis on clinical decision making in the emergency department. AB - The impact of a rapid streptococcal screening test (RSS) on clinical decision making in the management of patients with acute pharyngitis was evaluated. Physicians managing 95 ambulatory patients with the complaint of sore throat were asked to estimate the probability of group A beta-hemolytic streptococcal pharyngitis (GRABS) in each patient and whether they intended to treat with antibiotics both before and after the results of the RSS were known. Simultaneous throat cultures were obtained for 80 patients at the discretion of the treating physicians. Regression analysis revealed that the RSS result was an important independent predictor for the posttest decision to treat with antibiotics and for the estimated probability of disease. The mean absolute log-likelihood ratio was used to quantify the effect of the RSS on diagnostic certainty; a greater contribution to diagnostic certainty occurred when the RSS was positive. Physicians would have prescribed an antibiotic 49 times without the benefit of the RSS and prescribed an antibiotic 48 times given the RSS result. Without the RSS, the treatment decision contradicted the throat culture result in 25 cases. With the RSS, this occurred in 26 cases. The RSS, while influencing decision making, especially when positive, did not decrease the use of antibiotics. PMID- 1865781 TI - Physicians' risk attitudes, laboratory usage, and referral decisions: the case of an academic family practice center. AB - Individual differences in physicians' laboratory use and referral rates are important aspects of practice variation that have real financial and health consequences. A way to explain these differences is needed. In this empirical study, physicians' risk attitudes (measured on a multidimensional scale) are shown to be good predictors of use rates for certain specific laboratory procedures, but not good predictors of physicians' referral rates. A 15-item survey form that measured risk-taking attitudes in the financial, health, social, and ethical domains was administered to all clinical faculty at an academic family practice center (n = 14). Each physician's utilization rates for the 17 most frequently ordered laboratory procedures were calculated for all patient visits for one calendar year. Overall referral rates were calculated for the same period. Physicians' risk attitudes (12 completed the survey) accounted for over 50% of the variance for several of the laboratory procedures. For example, the rank-order correlation between the complete blood count utilization rate and a Likert-scale item measuring physicians' propensity to take physical risks was 0.91 (p less than 0.001). The details of these findings help to explain an important component of practice variation. PMID- 1865783 TI - Festschrift: In honor of Lee Lusted. PMID- 1865782 TI - The healthy-years equivalents: how to measure them using the standard gamble approach. AB - The healthy-years equivalent (HYE) is a measure of outcome of health care programs that combines two outcomes of interest: quality of life and quantity of life. Unlike QALYs (quality-adjusted life years) HYEs fully represent patients' (or other individuals') preferences, as a result of the way they are calculated from each individual's utility function. The authors suggest an algorithm to measure the HYE of any given lifetime health profile. The algorithm is based on the classic standard gamble method to measure individuals' preferences under uncertainty, and consists of two lottery questions. Algorithms for the general case (any given lifetime health profile) and a simpler case--the chronic health state case--are provided, as is a modification of the algorithm aimed at shortening the length of the interview when an individual is faced with many possible lifetime health profiles. In addition, two questions are addressed. The first is theoretical and deals with the existence of HYE: do all lifetime health profiles, which are preferred to death, have hypothetical equivalents that can be measured in healthy years? The second is empirical and deals with the reproducibility of the measures obtained by using the measurement technique suggested. This is needed because the technique employs a combination of lottery questions that had not previously been used together. The results of an experiment performed to test the reproducibility of the measures were satisfactory. PMID- 1865784 TI - The clearing "haze": a view from my window. PMID- 1865785 TI - The area under the ROC curve and its competitors. AB - The area under the receiver operating characteristic (ROC) curve is a popular measure of the power of a (two-disease) diagnostic test, but it is shown here to be an inconsistent criterion: tests of indistinguishable clinical impacts may have different areas. A class of diagnosticity measures (DMs) of proven optimality is proposed instead. Once a regret(-like) measure of diagnostic uncertainty is agreed upon, the associated DM is uniquely defined and, indeed, calculable from the ROC curve configuration. Two scaled variants of the ROC are introduced and used to advantage in the analysis. They may also be helpful to students of medical decision making. PMID- 1865786 TI - Research commentary: research critique and utilization. PMID- 1865787 TI - Prenatal drug exposure: a growing problem for families. PMID- 1865788 TI - From the Psych/Mental Health Council. New domestic violence legislation; new hope for victims of domestic violence. PMID- 1865789 TI - What are subjects of bargaining? PMID- 1865790 TI - From the Psych/Mental Health Council. Home sweet home. PMID- 1865791 TI - Research commentary: from concept to reality research critique and utilization. PMID- 1865792 TI - Self-evaluation of skills as a method of assessing learning needs for continuing education. AB - Identification of self-perceived learner needs is important in continuing education programmes for health professionals. This paper describes the use of a self-evaluation skill inventory as a method of determining priorities for continuing education of a category of middle-level health professionals. PMID- 1865793 TI - Do you know? An opportunity to assess how up-to-date you are with the medical education literature. PMID- 1865794 TI - How to share control with workshop participants. AB - The authors discuss the five steps they have used to share control with participants over the planning, implementation and evaluation of a workshop: (1) establish a co-operative learning climate; (2) provide resources for participants to identify their individual learning needs; (3) assist participants in organizing learning groups and defining objectives for each workshop session; (4) provide support for participants to manage the workshop sessions themselves; and (5) encourage participants to reflect on and evaluate their learning. PMID- 1865795 TI - Practical reform of preclinical education: core curriculum and science projects. AB - This essay proposes reform of the preclinical curriculum which is seen as deficient in both content and method. The period of preclinical study should have a dual purpose: to provide a vocational training in basic scientific knowledge essential to good clinical practice, and to educate medical students in the methods and skills of science. These purposes are best separated. The vocational element constitutes a core curriculum which could be constructed from a consideration of the basic scientific knowledge used by clinicians in their medical practice. A core curriculum could be prepared and examined on a national basis, and would provide a means for quality control of medical education. The timetable space thus liberated would be used for project work in medical sciences, using the teaching methods of science degrees. The proposed curriculum combines the discipline of vocational relevance with the educative potential of an honours BSc, but with no requirement for increased resources or alterations in manpower. It may be seen as a shift from theory towards practice during preclinical study. Strategies for introducing such a system are discussed. PMID- 1865796 TI - Achievement of objectives: internal medicine fourth year clinical clerkship. AB - The clinical clerkship in Canadian Medical Schools is intended to provide senior medical students with opportunities to gain practical knowledge of clinical medicine, develop technical skills, learn to use judgement and experience first hand clinical decision making. Assessment of rotations in internal medicine were undertaken in order to understand more fully the nature of medical clerkship experiences. We found that medical clerks in our programme were exposed to a high proportion of undifferentiated problems and an adequate case mix. They performed a wide range of technical procedures. There were, however, certain gaps in the clerks' experiences both in the specialty areas, and in therapeutic and technical procedures. Recognition of these gaps in the clerkship experiences suggest that further deliberation of goals and objectives is required and issues of achievement of competencies need to be addressed. PMID- 1865797 TI - Student contact with patients in hospital: frequency, duration and effects. AB - Student-patient contacts on the wards were monitored by having students keep daily logs of patient contacts during a 5-week period of routine clinical attachments in a teaching hospital. After being discharged patients were followed up by postal questionnaire. Results indicated that on average students spend substantially less time with patients than is allowed for in the curriculum. Variability in contact time was high both within and between attachments to different wards. Patient satisfaction with student contact was high. The duration of student-patient contact was not significantly related to patient satisfaction. There was a significant relationship between patient satisfaction and the number of different topics patients recalled discussing with students. PMID- 1865798 TI - The use of role-play in teaching medical students obstetrics and gynaecology. AB - There is a great need to review and critically assess medical education. Role play has seen increasing use as an educational tool. We investigated its role in a 'conventional speciality', Obstetrics and Gynaecology. This is a part of the medical curriculum where communication skills are particularly important, but difficult to learn in practice. Twenty-one medical students took part in three role-play case studies. An innovation we implemented was the use of 'time outs' which could be called at any time through a session. After the exercise students were required to complete a questionnaire designed to probe their attitudes towards the experience. The results indicate that this technique can be successfully used in teaching a conventional speciality. Unlike some previous studies we also found this to be a satisfactory tool in teaching the factual part of the course. We found the 'time out' innovation to be an important aid. We argue that there is an important niche for role-play in medical education. PMID- 1865799 TI - Using role-play to teach consultation skills--the Singapore experience. AB - Role-play by students has been adopted as a teaching method for learning consultational skills during a primary health care posting for fourth year medical students in the National University of Singapore. This article describes the construction of the framework used, and reports on its evaluation by both the students and their teachers. The overall response to the session by the students was positive. Suggestions were then solicited to make refinements to enhance its efficacy as a teaching tool. PMID- 1865800 TI - The way we teach otolaryngology in an integrated problem-based curriculum. AB - The University Science Malaysia, Penang, the third medical school in Malaysia, is following an integrated curriculum. In this curriculum, the students are taught the subject of otolaryngology from the second year of their course unlike the traditional schools where they are taught in the fourth or fifth year. This paper describes how otolaryngology is introduced in this integrated, problem-based curriculum. PMID- 1865801 TI - How we teach ... practical skills in an undergraduate medical curriculum: 5 years of experience at Gezira Medical School (Sudan). AB - An outline of an undergraduate course to teach medical students practical medical procedures early in their curriculum is described. Introduction of those skill as early as the second year has given the student ample time to practice those skills before graduation. Feedback has shown that the course has been successful in helping the students to master simple procedures by the time they graduate. Early demonstration of complicated skills has also facilitated the ability and confidence of the student to perform those skills during the internship. PMID- 1865802 TI - Twelve tips on providing handouts. PMID- 1865803 TI - Preceptors for an introduction to clinical medicine course: needs of volunteer and full-time faculty. AB - Recruiting clinicians to teach bedside skills is often a challenge for Introduction to Clinical Medicine (ICM) course co-ordinations. Little data is available concerning what motivates a faculty to participate in these programmes. Better understanding of these factors might allow enhanced faculty involvement. We surveyed full-time and volunteer faculty as to what forces promote and hinder participation as preceptors for an ICM course. Results documented that both faculty groups found student interactions and teacher fulfillment their major reward, with little perceived academic or patient recognition. Personal time limitations was the greatest deterrent to participation. Assessing faculty needs has allowed focused course changes and new activities to facilitate involvement. PMID- 1865804 TI - The evaluation of teaching in undergraduate psychiatric education: students' attitudes to psychiatry and the evaluation of clinical competency. AB - There is an increasing demand for improved skills by medical graduates in the psychosocial aspects of medical care. Psychiatrists as educators need to play an important role in the development and evaluation of education in many areas of the undergraduate curriculum in addition to the continuing education of graduates. In this review approaches to the evaluation of undergraduate psychiatric education are discussed with particular emphasis on students' attitudes to psychiatry. Key issues that remain to be addressed include the clarification of the most appropriate goals for undergraduate education in psychiatry, the most valid means of evaluating such educational programmes, particularly clinical competency and, finally, the many tasks in improving the status of the psychosocial aspects of medical care for students and their clinical teachers. PMID- 1865805 TI - Investigating stress levels of residents: a pilot study. AB - A pilot study of the levels of stress among residents was conducted in three departments in a university hospital prior to initiating a programme in stress management for residents. The Beck Depression Inventory, which is a brief, standardized self-report measure of depression, was given to residents in anaesthesiology, paediatrics and psychiatry. Six additional questions were asked about the functioning of peers and services residents would like to have available. Of the 113 residents surveyed, 16% were experiencing a mild mood disturbance. The researchers feel this is probably under-reported. Residents felt that about 15% of their colleagues were emotionally impaired; 10% may have a drug and/or alcohol problem; 12% were having marital problems. Eighty per cent of all residents studied said that they would attend support groups if they existed. Approximately 60% thought coping skills/stress management seminars would be useful, and 30% of the paediatric and anaesthesiology residents (60% of the psychiatry residents) said they would use confidential individual psychotherapy if it were available. PMID- 1865806 TI - How we teach ... key aspects of general practice using weekly seminars for GP trainees. AB - This article reports the author's experience of designing, teaching and evaluating a weekly lunchtime seminar series for Family Medicine Programme trainees in Gippsland. After reviewing the objectives of the seminar series and characteristics of the participants, the article outlines the process and content of the course. Particular emphasis is given to seven seminars on key aspects of general practice/family medicine, which highlight the differences between the models, concepts and attitudes of specialists and teaching hospitals, and those of general practice. Results of evaluations of seminar series from the beginning of 1986 to the present time are reported and discussed. Overall, the seminar series has been found to be effective in helping trainees to develop an appropriate understanding of key aspects of general practice/family medicine; facilitating the transition for trainees from hospital practice to general practice; and in encouraging active participatory learning. PMID- 1865807 TI - Pedicled radial forearm flaps for recalcitrant defects about the elbow. AB - Chronic, open wounds about the elbow frequently require flap coverage. Skin grafts, local transposition flaps, muscle transposition flaps, and two-staged pedicled flaps from the chest and abdomen as well as free tissue transfers have all been reported. Recalcitrant elbow defects in patients in whom these previous flaps have failed are especially challenging to the upper extremity reconstructive surgeon. We have successfully employed pedicled radial forearm flaps in three patients in whom one or more previous flaps have failed. PMID- 1865808 TI - Experience with calcium antagonists nitrendipine, diltiazem, and verapamil and beta 2-agonist salbutamol in salvaging ischemic skin flaps in rabbits. AB - This study investigated the efficacy of selected agents in the salvage of experimental skin flaps in rabbits after 21 hours of 25 degrees C ischemia. Calcium channel antagonists nitrendipine, diltiazem, and verapamil increased ischemic skin flap survival in rabbits from 33.3% for buffered saline infused controls to 71.4% (P less than 0.05), 71.4% (P less than 0.05), and 50.0% (not significant) respectively. The beta 2-adrenoceptor agonist salbutamol produced an increase in survival to 64.3%, which narrowly missed statistical significance. All four test agents invoked a vasodilatory response (greatest for nitrendipine, diltiazem, and salbutamol), a slight fall in blood pressure, and a small increase in heart rate. It is concluded that the vasodilatory response in the microcirculation of the ischemic flap helped to minimize the risk of occlusion due to thrombosis or cell sludging during reperfusion, thus leading to improved flap survival. PMID- 1865809 TI - Failure to obtain long-term patency after implantation of fibrous polyurethane prostheses in the carotid arteries of rabbits. AB - Fibrous polyurethane prostheses were implanted in the carotid arteries and aortae of New Zealand white (NZW) and Chinchilla (CHIN) rabbits. No immediate post implantation patency was obtained after implantation in the carotid arteries in NZW rabbits. In CHIN rabbits patency up to 1 week was obtained after carotid implantation. Attempts to increase patency rates by administration of 20 mg/kg body weight/day of both dipyridamol (DIP) and acetyl-salicylic acid (ASA) p.o., starting the week before implantation, had an adverse effect; prostheses became occluded within a few hours after implantation. Coagulation tests (Lee and White, Am J Med Sci 145:495-503, 1913) carried out with blood drawn from CHIN rabbits revealed hypercoaguability after administration of either 10 or 20 mg/kg body weight/day of both DIP and ASA compared to pre-medication values. Prostheses implanted in the aortae of both strains remained patent without anti-platelet aggregation therapy for a 3-month observation period. It is concluded that in the NZW rabbit carotid implantation was not successful due to severe spasmic reactions and that in CHIN rabbits only very short-term patency could be obtained both with and without administration of 10 or 20 mg/kg body weight/day medication DIP and ASA. PMID- 1865810 TI - Free vascularized fibula transfer in the management of congenital pseudarthrosis of the tibia. PMID- 1865811 TI - Brachial plexus microsurgery in children. AB - From this review, the following points have emerged: 1. The typical obstetrical palsy is a traumatic lesion caused by forced lowering of the shoulder during delivery. 2. While the lesion may affect all the roots, the upper roots are usually ruptured, whereas the lower roots (if involved) are always avulsed. 3. Spontaneous recovery is possible, but its quality depends on how early recovery of previously paralyzed muscles begins. If the biceps have not started to recover by 3 months, the final result will be poor. It is at this time interval that a surgical decision should be made. 4. Surgical repair is always possible, usually by grafting, though repair can be difficult if significant numbers of avulsions have occurred. 5. The results of surgical reconstruction are better than are the results of spontaneous evolution, at least in those patients who reach the age of 3 months without evidence of recovery of the biceps. For example, more than half of the patients recover a nearly normal shoulder after grafting C5, C6 lesions in Gilbert's series, whereas in the same control population of patients, none achieved this result spontaneously. 6. Palliative treatment of the sequelae of birth palsies is difficult, and the results obtained are rarely totally satisfactory. It is for these reasons that the initial surgical intervention should be on the plexus itself in those instances meeting the criteria established above. It is important to make this decision as quickly as possible before neuroplasticity is diminished and joint contractions have occurred. PMID- 1865812 TI - Toe transfer for congenital hand defects. AB - Toe-to-hand transfer is a well-established reconstructive option for certain congenital hand anomalies. It is the only technique which can add growth potential to the immature skeleton. Toe transfer is best suited for constriction ring amputations, which have relatively normal proximal anatomy. Transfers should be performed early in life to avoid lack of cortical integration of the new part. Anatomic variations of both hand and foot are often encountered, which influence both operative approach and functional prognosis. Indications, techniques, and complications are reviewed. PMID- 1865813 TI - Free vascularized whole joint transfer in children. AB - Reconstruction of the traumatized finger joint with epiphyseal destruction has long been problematic. Since free vascularized whole joint transfer was introduced as a treatment for joint and epiphyseal destruction, this procedure has been selected as an alternative treatment because it may provide a growing epiphysis. We have reviewed our series of 19 joint transfers. Mean age at operation was 6.2 years (range 3 to 12). Average active range of motion was 31 degrees/61 degrees for the group with posttraumatic reconstruction (n = 12) and 21 degrees/43 degrees for the group with reconstruction of a congenital deformity (n = 7), with an overall average of 27 degrees/54 degrees. Average range of motion following transfer of an metatarsophalangeal (MTP) or metacarpophalangeal (MCP) joint to an MCP joint position was 39 degrees/75 degrees (n = 4); proximal interphalangeal (PIP) to PIP transfer was 22 degrees/39 degrees (n = 13); and PIP to MCP transfer was 38 degrees/51 degrees (n = 2). The proximal phalanges in MCP joints transferred to the MCP position grew an average of 7.0 mm, and the middle phalanges of joints transferred to the PIP position grew 4.3 mm. Almost normal growth was observed in all transferred joints except two that showed premature epiphyseal closure. Indications for this procedure and techniques to improve range of motion are described. PMID- 1865814 TI - Free tissue transfer for reconstruction of traumatic limb injuries in children. AB - Free tissue transfer was used for the reconstruction of soft tissue defects in 94 children. Of the 127 procedures performed, the latissimus dorsi, scapular skin, lateral arm skin, rectus abdominis, and gracilis were used with the greatest frequency. The microsurgical success rate was 96%. Microsurgical failures were repeated, successfully, and in all cases the limbs were salvaged. Other than having to deal with decreased vessel size and avoiding continuous suture lines, there appears to be little difference in technique or outcome of free tissue transfer when compared to adults. PMID- 1865815 TI - Replantation in children. AB - The authors have replanted 162 parts in 120 children over the past 15 years. The youngest patient, undergoing successful replantation, was aged 7 months, 3 weeks. Unlike an adult, any child suffering a traumatic amputation should be considered for a possible replantation. Replantation should consist of minimal bone shortening to preserve epiphyseal plates, with repair of all severed structures. Longitudinal K-wires usually provide adequate fixation. Our survival rate for complete replantation in children under the age of 16 years is 77%. Long-term study showed that continued skeletal growth occurred and the digit attained 81% of normal longitudinal length at maturity. Recovery of sensibility in the replanted digit is nearly as good as for isolated digital nerve repair. Patient and parent satisfaction is high when replantation is successful, with uniform approval of the extensive effort required. PMID- 1865816 TI - Major limb replantation in children. AB - This retrospective study evaluated patients under 18 years of age who underwent major limb replantation between 1976 and 1989 at Louisville Hand Surgery. The age of the 15 patients followed for between 1 and 8.5 years (mean 4.2 years) ranged from 2 to 17 years (mean 9.8). Of amputations, 40% were guillotine, 40% were limited crush-avulsions, 7% were extended crushing, and eight were of an upper extremity and seven of a lower extremity. Average warm/total ischemia times were 4.8/14.8 hr in failures and 1.1/7.5 hours in successful replantation. Overall limb survival was 87%. Among the patients, 93% felt that their replanted limb functioned and looked better than a prosthesis; 87% of patients had a sensory recovery of more than S2+ in the lower extremity or S3 in the upper extremity; and 38% of upper extremity replantation patients had two-point discrimination of less than 15 mm. PMID- 1865817 TI - Rat vein graft diameters. PMID- 1865818 TI - Isotopic determination of fibronectin synthesis in humans. AB - Fibronectin is an opsonic protein that, among other functions, activates the reticuloendothelial system. Accurate measurement of its rate of synthesis is necessary to more fully understand its physiological role in normal and pathological conditions. We have determined the rate of fibronectin synthesis in three normal volunteers using a primed-constant infusion of 15N-glycine and 1,2 13C-leucine, and measuring the incorporation of the isotopes into the protein over 5 days of infusion. In nine additional subjects, the fractional synthetic rate (FSR) of fibronectin was calculated during a 24-hour infusion using urinary hippurate and plasma alpha-ketoisocaproic acid enrichment to represent the precursors for incorporation of labeled glycine and leucine, respectively, into fibronectin. The FSR using glycine and leucine was 1.56 +/- 0.14 and 1.29 +/- 0.04 (%/h), respectively, in the 5-day infusion study, and 1.56 +/- 0.10 versus 1.83 +/- 0.09 (%/h), respectively, in the 24-hour study. The results of the 5-day infusion of 15N-glycine justify the use of urinary hippurate to reflect the precursor enrichment for the determination of the FSR of fibronectin during a shorter (less than 24 hour) infusion period. PMID- 1865819 TI - Ethanol inhibits human bone cell proliferation and function in vitro. AB - The direct effects of ethanol on human bone cell proliferation and function were studied in vitro. Normal human osteoblasts from trabecular bone chips were prepared by collagenase digestion. Exposure of these osteoblasts to ethanol in concentrations of 0.05% to 1% for 22 hours induced a dose-dependent reduction in bone cell DNA synthesis as assessed by incorporation of 3H-thymidine. After 72 hours of ethanol exposure in concentrations of 0.01% to 1%, protein synthesis as measured by 3H-proline incorporation into trichbroacetic acid (TCA)-precipitable material was reduced in a dose-dependent manner. Human bone cell protein concentrations and alkaline phosphatase total activity were significantly reduced after exposure to 1% ethanol for 72 hours, but not with lower concentrations of ethanol. This reduction in osteoblast proliferation and activity may partially explain the development of osteopenia in humans consuming excessive amounts of ethanol. PMID- 1865820 TI - Dose-response effects of glucose, insulin, and glucagon on mouse pre-embryo development. AB - The diabetic state, as well as elevated culture media glucose level (950 mg D glucose/dL) per se, significantly retards in vitro development of mouse pre implantation embryos from a two-cell stage to blastocyst stage; maternal insulin therapy to diabetic mice reverses this impairment. This study was undertaken to assess (1) whether less extreme elevation of the media glucose concentration would also impair development, and (2) whether elevated culture media insulin or glucagon levels would alter development. Two-cell pre-embryos were recovered from B6C3F1 mice that had been stimulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hGG), mated, and killed 48 hours later. Pre embryos were observed in culture at 24-hour intervals for a total of 72 hours at four glucose levels: 110 (n = 108), 220 (n = 101), 440 (n = 65), and 950 (n = 106) mg D-glucose/dL. Impairment in progression of development was noted at each time period; compared with development in 110 mg glucose/dL, the distribution of development was significantly different at 24 hours (chi 2 = 60.1, P less than .001), at 48 hours (chi 2 = 36.7, P less than .001), and at 72 hours (chi 2 = 45.1, P less than .001). Rate of development as assessed by ANOVA was also significantly reduced at increasing glucose levels (P less than .0001), with Duncan Multiple Range test demonstrating differences between development at higher glucose levels in the comparison of development in 110 mg/dL versus 440 mg/dL and 950 mg/dL, and at 220 mg/dL versus 950 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865821 TI - The association of lipid abnormalities with tissue pathology in human osteoarthritic articular cartilage. AB - Articular cartilage is one of very few body tissues uniquely characterized as having substantial stores of lipid deposits. Lipid droplets are naturally accumulated by chondrocytes and individual fatty acids have been shown to have protective as well as deleterious effects on cartilage degradation in animal models of degenerative joint disease. As a means to better assess the role of lipids in human joint pathology, a comparative analysis of fatty acids was undertaken in small segments of osteoarthritic articular cartilage. The data were assessed in terms of chondrocyte synthetic activity and histological determination of disease severity. The distribution profile of individual fatty acids in normal and osteoarthritic specimens remained constant, with palmitic, oleic, and linoleic acids representing 85% of the total fatty acids. In contrast, levels of total fatty acids were markedly increased in association with increasing degree of lesion severity. Compared with tissue from normal-aged joints, grade 0 to 1 mild lesions had elevated levels of total fatty acids, essential fatty acids, and chondrocyte synthetic activity of 80%, 312%, and 393%, respectively. More severe tissue involvement (grade 6 to 9), was associated with even greater increases of 440%, 1,100%, and 1,150%, respectively. No change was noted in cholesterol content in any tissue. The accumulation of arachidonic acid was greater than the proportional increase in total fatty acid content and was primarily distributed into the neutral lipid fraction, where it constituted almost 62% of the fatty acid level in tissues of moderate lesion severity. There was an association of lipid accumulation in general and arachidonic acid in particular with histological severity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865822 TI - Dihydroergotamine as a pharmacologic euglycemic clamp in the surgically traumatized rabbit. AB - We assessed the utility of a pharmacologic euglycemic clamp technique by examining the metabolic and hemodynamic changes brought about by administration of dihydroergotamine (DHE) prior to anesthesia and operative trauma in the rabbit. New Zealand white rabbits received an intramuscular injection of 0.15 mg DHE/kg body weight 20 minutes before general anesthesia and minor surgical trauma, which consisted of carotid artery and jugular vein catheterizations followed by femoral artery and vein cannulations. Arterial blood was sampled every 20 minutes and assayed for glucose, lactate, nonesterified fatty acids (NEFA), and insulin. Rates of hindlimb skeletal muscle glucose uptake (Rg) and blood flow were determined 2 hours after the initial administration of DHE. DHE did not produce any effects on heart rate, blood pressure, blood flow, and Rg when compared with control animals. Liver glycogen levels were significantly higher after DHE treatment (140 +/- 31.4 v 34 +/- 9.6 mumol/g dry weight, P less than .01). Those animals receiving DHE had significantly lower and more stable plasma glucose levels than untreated animals (ranges, 5 to 9 v 7 to 22 mumol/mL plasma) and circulating NEFA were also lower and less variable (ranges, 0.1 to 1.0 v 0.1 to 2.0 muEq/mL plasma). The results show that DHE prevents stress induced hyperglycemia in vivo in the rabbit without altering glucose uptake by skeletal muscle. The technique provides control over circulating glucose levels during the study of skeletal muscle glucose uptake without apparent negative physiologic effects. PMID- 1865823 TI - Intra-abdominal fat is associated with decreased insulin sensitivity in healthy young men. AB - To distinguish the relative role of intra-abdominal and subcutaneous abdominal fat in metabolic aberrations in upper body fat localization, we measured the relationship between regional fat distribution and insulin sensitivity in nine young men (28.6 +/- 0.7 years; body mass index [BMI], 24.7 +/- 1.3 kg/m2). Regional fat distribution was measured by anthropometric measurement and computed tomography (CT). Insulin sensitivity was measured by euglycemic hyperinsulinemic glucose clamp. Insulin sensitivity, expressed as the ratio of rate of glucose utilization to the mean plasma insulin concentration during the second hour of glucose clamp (M/I) was negatively correlated with BMI (r = -.91, P less than .001), waist to hip girth ratio (WHR) (r = -.80, P less than .01), subcutaneous abdominal fat area (r = -.90, P less than .001), and intra-abdominal fat area (r = -.88, P less than .01). Stepwise forward regression analysis showed that in addition to BMI, intra-abdominal fat area was a significant correlate of decrease in insulin sensitivity. These findings suggest that intra-abdominal fat play an important role in decreasing insulin sensitivity, even in healthy young men. PMID- 1865824 TI - Plasma levels of lathosterol and phytosterols in relation to age, sex, anthropometric parameters, plasma lipids, and apolipoprotein E phenotype, in 160 Dutch families. AB - In this study, the relation of plasma levels of lathosterol (an indicator of whole body cholesterol synthesis) and plant sterols (indicator of cholesterol absorption) with age, sex, weight, height, plasma lipids, and lipoproteins, and with apolipoprotein (apo) E phenotype, was investigated in a group of 160 nuclear families consisting of twins living with their parents. Lathosterol was higher in fathers than in mothers, but not different between boys and girls. In each of these four groups, there was a strong correlation with plasma and low-density lipoprotein (LDL)-cholesterol and -triglyceride, as well as with body weight, but not with height or high-density lipoprotein (HDL)-cholesterol. In adults, lathosterol was inversely correlated with plant sterols. Lathosterol was higher in children with E4/3 phenotype than in those with E3/3 or E3/2; in adults, lathosterol did not differ among the various E phenotypes. The plasma levels of the two plant sterols, campesterol and beta-sitosterol, were highly correlated with each other, and also with plasma or LDL-cholesterol, in each of the four groups. Plant sterols were higher in adults or children with E4/3 phenotype as compared with those with other phenotypes. In multivariate analysis (performed separately for two groups of adults and children) plasma cholesterol, plasma plant sterols, plasma triglycerides, and weight were found to make significant contributions to the variation of lathosterol in all groups, and E phenotype and sex only in one group, while age did not contribute in any group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865825 TI - Metabolism of aspartame and its L-phenylalanine methyl ester decomposition product by the porcine gut. AB - The intestinal metabolism of aspartame (N-L-alpha-aspartyl-L-phenylalanine methyl ester; APM) and its L-phenylalanine methyl ester (PME) decomposition product was evaluated in six young pigs. Equimolar doses (2.5 mmol/kg body weight) of APM, PME, and L-phenylalanine (PHE) administered to the proximal jejunum produced similar increases in portal blood PHE concentrations. Methanol, nondetectable in portal blood after PHE ingestion, increased markedly after administration of either APM or PME. Portal blood aspartate concentrations were unchanged after PME and PHE administration, but increased significantly after APM administration. Increases in portal blood PHE concentrations were significantly greater than were increases in aspartate concentrations following APM administration. Neither APM, PME, nor aspartyl-phenylalanine (AspPhe) were detected in portal or vena caval blood following administration of any test compound. Steady-state perfusion of the small intestine with APM showed a net intraluminal appearance rate of AspPhe at 36% of the disappearance rate of APM. During steady-state PME perfusion, PHE had a significantly greater net appearance rate than during APM perfusion. Methanol appearance rates were slightly, but not significantly, higher during PME than during APM perfusions. The data suggest that (1) APM is hydrolyzed to AspPhe and both APM and PME are hydrolyzed to their constituent amino acids and and methanol prior to entering the portal circulation; (2) AspPhe is an important intraluminal intermediate in aspartame metabolism; and (3) aspartate is rapidly metabolized by the enterocyte. PMID- 1865826 TI - The effect of lovastatin treatment on low-density lipoprotein hydrated density distribution and composition in patients with intermittent claudication and primary hypercholesterolemia. AB - The effects of lovastatin treatment on density distribution and composition of low-density lipoproteins (LDL) were studied using a density gradient ultracentrifugation method in 35 hypercholesterolemic patients with severe peripheral vascular disease. Lovastatin caused a 32% mean reduction in LDL particle mass and a 36% reduction in LDL cholesterol. The cholesteryl ester to apolipoprotein (apo) B, free cholesterol to apo B, and phospholipid to apo B weight ratios in LDL decreased significantly during treatment (P less than .01, P less than .01, and P less than .001, respectively). The effect on plasma triglycerides (Tg) was not uniform. Plasma Tg levels decreased in 25 patients, but increased in 10 patients. Since plasma Tg level influences the LDL density distribution and composition, the patients were also subgrouped and analyzed according to change in plasma Tg. In those with increased plasma Tg, the light LDL particles were reduced more and the dense particles less compared with patients with decreased Tg. The mean Tg content of LDL increased (from 7.7% to 9.3%; P less than .05) and the weight ratio of core lipids (cholesteryl ester/Tg) in LDL decreased (from 4.57 to 3.44; P less than .01) in patients with increased plasma Tg during treatment. The results indicate that the change in plasma Tg (decrease or increase) determined the qualitative changes in LDL observed during lovastatin treatment. PMID- 1865827 TI - Bromocriptine inhibits the seasonally occurring obesity, hyperinsulinemia, insulin resistance, and impaired glucose tolerance in the Syrian hamster, Mesocricetus auratus. AB - Seasonally obese-hyperinsulinemic female Syrian hamsters were injected daily with bromocriptine or saline for a period of 34 days to test for effects of bromocriptine on body fat store levels, hepatic triglyceride secretion, glucose tolerance, and plasma insulin and glucose concentrations. The effects of bromocriptine on body fat store levels, as well as on plasma insulin and glucose concentrations, in seasonally obese hamsters were compared with the levels of body fat, plasma insulin, and plasma glucose observed in seasonally lean hamsters. Bromocriptine treatment substantially improved glucose intolerance and reduced the total and stimulated areas under the glucose tolerance curve by 33% after 14 days of treatment. After 34 days of treatment, bromocriptine reduced body fat store levels by 36% and hepatic triglyceride secretion by 40% without any concurrent change in food consumption. Furthermore, bromocriptine reduced the plasma insulin level by 70%, while slightly reducing plasma glucose concentration (ie, 68% reduction in the insulin to glucose ratio). The reductions of body fat, plasma insulin, and plasma insulin to glucose ratio produced by bromocriptine in seasonally obese hamsters are equivalent to those observed in seasonally lean hamsters. Shifts in phase relationships of circadian neuroendocrine rhythms have been demonstrated to regulate annual cycles of metabolism in vertebrates, including the Syrian hamster. The effects of bromocriptine can also be explained as an alteration of such a circadian mechanism. PMID- 1865828 TI - The hepatocellular thyroid status of uremic rats estimated from the abundances of thyroid hormone-dependent nucleoplasmic proteins. AB - Although the serum thyroxine (T4) and triiodothyronine (T3) concentrations of uremic rats are commensurate with moderate hypothyroidism, their thyroid status at the tissue level remains controversial. To help establish the hepatocellular thyroid status of uremic rats, a novel tissue marker (nuclear protein abundances) was evaluated in uremic rats (U), hypothyroid rats (H), and hypothyroid uremic rats (HU). Uremia was established by five-sixths nephrectomy. Moderate hypothyroidism was established by partial thyroidectomy or by provision of drinking water supplemented with propylthiouracil and T4. Normal rats (N) and pair-fed, sham-operated rats (1 to 3 weeks after surgery) served as controls. Animals were killed 1 to 5 weeks postoperatively. The following values were obtained 5 weeks after surgery, at which time the total and free serum T4 and T3 levels of the hypothyroid rats (H) were equivalent to those of the uremic rats (U). Total T4 (micrograms/dL +/- 1 SD): N, 5.4 +/- 1.7; H, 2.2 +/- 0.5; U, 1.9 +/ 1.5; HU, 0.5 +/- 0.0. Free T4 (ng/dL +/- 1 SD): N, 535 +/- 165; H, 126 +/- 37; U, 135 +/- 89; HU, 26 +/- 1. Total T3 (ng/dL +/- 1 SD): N, 63 +/- 20; H, 39 +/- 14; U, 38 +/- 18; HU, 13 +/- 4. Free T3 (ng/dL +/- 1 SD): N, 7.83 +/- 3.00; H, 3.87 +/- 1.05; U, 3.47 +/- 1.73; HU, 0.94 +/- 0.47. Hepatocellular thyroid status was estimated from the relative abundances of two nucleoplasmic proteins on polyacrylamide gel electrophoregrams.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865829 TI - Insulin sensitivity and insulin clearance in human immunodeficiency virus infected men. AB - To test whether clinically stable human immunodeficiency virus (HIV) infection, like other infections, is associated with insulin resistance and increased insulin clearance, we measured the sensitivity to insulin and insulin clearance using the euglycemic insulin clamp technique in 10 clinically stable outpatients with symptomatic HIV infection (Centers for Disease Control [CDC] group IV) and 10 healthy controls. During administration of 0.8 and 4 mU insulin.kg-1.min-1, HIV-infected men had 40% (P less than .02) and 83% (P less than .01) higher rates of insulin clearance when compared with healthy controls. Despite significantly lower steady-state insulin concentrations (42 +/- 2 v 52 +/- 4 microU/mL, P less than .05, and 255 +/- 17 v 392 +/- 14 microU/mL, P less than .001, patients v controls), patients and controls had similar total glucose uptake (7.99 +/- 0.81 v 7.92 +/- 0.44 mg.kg-1.min-1 and 14.00 +/- 0.81 v 13.65 +/- 0.65 mg.kg-1.min-1, patients v controls). In the postabsorptive state, no differences were found between patients and controls in insulin levels (7 +/- 1 microU/mL in both) and endogenous glucose production (2.52 +/- 0.07 and 2.24 +/- 0.17 mg.kg-1.min-1, respectively), but plasma glucose levels in the patients (5.02 +/- 0.15 mmol/L) were significantly lower when compared with controls (5.46 +/- 0.14 mmol/L, P less than .05). The results indicate that HIV-infected men have increased rates of insulin clearance and increased sensitivity of peripheral tissues to insulin, which makes HIV infection unique with regard to glucose and insulin metabolism. PMID- 1865830 TI - Effect of Aeromonas proteases on the binding of Aeromonas hydrophila strains to connective tissue proteins. AB - 125I-labelled connective tissue protein binding to cells of Aeromonas hydrophila, A. caviae, and A. sobria strains isolated from diseased fish, was correlated with the Aeromonas protease degradation of 125I-labelled collagen types I and IV, fibronectin and laminin, immobilized on tissue culture microtitre plates. An inverse relation between 125I-labelled connective tissue protein binding to cells of Aeromonas strains and proteolytic degradation of immobilized connective tissue proteins by Aeromonas proteases was established. Inhibition of the Aeromonas proteolytic activity by protease inhibitors enhances the 125I-labelled connective tissue protein binding to cells of Aeromonas hydrophila strains. Culture conditions were found to influence both expression of proteolytic activity and binding properties. PMID- 1865831 TI - Changes in hydrolytic enzyme activities in armadillos infected with Mycobacterium leprae. AB - The activities of hydrolytic enzymes in various organs of armadillos infected with Mycobacterium leprae were compared with those in normal armadillos. Except for aspartate aminopeptidase and esterase, the levels of the other enzymes in liver, spleen and inguinal lymph nodes were significantly higher in armadillos infected with M. leprae compared with those in non-infected ones. These enzymes levels were at a maximum when the animals were sacrificed 22 to 30 months post inoculation, a period when the bacterial load in the animals had also reached a maximum. Animals infected with M. leprae but not showing any signs of disseminated infection behaved similar to those in the non-infected group. The observed changes in enzymatic activities were not due to bacterial enzymes and so can be related to tissue damage caused by M. leprae. PMID- 1865832 TI - Purification, characterization and antimicrobial properties of an antibiotic (wassumycin) from Streptomyces species 215. AB - A yellow amorphous compound, wassumycin, was isolated from an unidentified strain of Streptomyces. Wassumycin inhibited the growth of several species of human and animal pathogenic bacteria especially Clostridia. Wassumycin also inhibited the growth of HeLa cells, and showed good antitumour activity against experimental mouse tumours such as L1210, P388 leukaemias, and B16 melanoma. On the basis of the chemical and antimicrobial properties, the antibiotic appeared similar to the chromomycins and olivomycins, but its ultraviolet, infrared, and proton magnetic resonance spectra differed from theirs significantly. PMID- 1865833 TI - Altered lipid metabolism in parvovirus-infected cells. AB - A broad spectrum of cell lipid alterations are known to occur as a consequence of various viral infections. These changes include inhibition of lipid synthesis, stimulation of lipid synthesis and changes in the proportions of various lipids. The current study examined the effects of two parvoviruses on lipids of rat kidney (NRK) cells. Cells were infected with H-1 or Kilham rat virus (KRV) and the effects on 14C-acetate incorporation determined. Results showed that H-1 virus rapidly inhibited lipid formation (in 1 h) while KRV produced a similar effect beginning around 8 h. Pretreatment of the cells with cycloheximide did not alter this response. Fatty acid analysis by gas chromatography did not reveal major alterations in this component of total cell lipids although some fatty acids became undetectable by 18 h post-infection. The data suggest that these parvoviruses, especially H-1 virus, are able to rapidly alter lipid formation following infection and that this effect may be mediated by a virion component. PMID- 1865834 TI - Flow microcalorimetry investigation of the influence of glucose and maltose on the growth of Streptococcus agalactiae and the production of CAMP factor (protein B). AB - Microcalorimetric investigations of the growth of Streptococcus agalactiae and production of CAMP factor were performed in combination with the photometric estimation of bacterial mass and the bioluminescent measurement of extracellular ATP in trypticase peptone-yeast extract broth supplemented with either 2% maltose or glucose. Maltose was found to be a more efficient energy substrate than glucose, providing more energy and C-atoms to the growing cells. In the presence of maltose, the metabolic activity of S. agalactiae was more efficient and better balanced than in that of glucose. Bacterial cells growing in maltose-containing medium used more substrate energy for their anabolic activities, while cells growing in the presence of glucose lost more substrate energy in the form of heat. The addition of 0.2% NaHCO3 to the carbohydrate-supplemented medium enhanced the efficiency of the anabolic activity of growing cells, but did not promote bacterial growth. Microcalorimetry should be considered as a useful alternative as well as a complementary method for the optimization of the growth media or growth conditions. PMID- 1865835 TI - Everyday diagnostics--a critique of the Bayesian model. AB - In recent years Bayesian probability calculus and Bayesian decision procedures have been recommended for use in clinical medicine. The author investigate everyday diagnostics asking if it takes place in a reality that meets the conditions of the method. He finds it does not. Above all we lack that strict randomness essential for probability calculus and, further, evaluation of utility easily becomes disputable, not to say unethical. The measures constructed for neutralizing these discrepancies between model and reality demand great resources. Yet, they are not enough to permit the clinician to refrain from supervising the consequences of his decisions as carefully as he has always done. A different method, a different model is wanted. PMID- 1865836 TI - Melatonin: a chronobiotic with anti-aging properties? AB - Recently, it has been reported that melatonin administration extends the lifespan of mice, a finding which supports previous research on the effects of pinealectomy and pineal extract administration. The prolongation of lifespan by melatonin has been interpreted in favour of an upregulation of the immune system as well as due to anti-stress properties of melatonin acting via the brain opioid system. In this paper we offer an alternative explanation of melatonin's anti aging effect: the circadian pacemaker system has a diminished amplitude with age as indexed by a decrease in circulating melatonin levels. Stability of the circadian system correlates with its amplitude and loss of circadian amplitude produces lability which, in turn, leads to internal temporal disorder. Internal temporal disorder may be a precursor of disease states. Exogenous melatonin increases the amplitude of the circadian pacemaker system by feedback onto that system. The hypothalamic suprachiasmatic nuclei are thought to be the mammalian biological clock in the brain and have high concentrations of melatonin receptors. Therefore, melatonin administration in pharmacological doses may prevent aging symptoms by acting at the level of the circadian pacemaker's amplitude. PMID- 1865837 TI - Dissipative structure and the mind-body problem. AB - A theory explaining the link between mind and body is presented which depends upon viewing personal awareness as a figure against the ground of infinity. It is proposed that a tendency toward dissipation, in tension with an opposite tendency toward structural integrity, determines both the 'illumination' and specificity of awareness. Mind, as an aspect of the awareness bubble, is envisioned as influencing the body via a regressive discrepancy in relation to the current organization of the body mass - a conclusion derived from the fact that the origin of the tension between structure and its dissipation extends regressively back to the time when self was infinite or boundless, i.e., non-existent. This regressive discrepancy drives behavior in an expectable and therefore visible direction [corrected]. The entire thesis rests upon viewing reality as fundamentally personal, such that the linkage between a sensory field and neural activity can be explained on the basis of a simple gap between structure and its dissipation. The significance of this viewpoint for understanding the brain is briefly discussed. PMID- 1865838 TI - Scaling concepts in cellular and subcellular dynamics. AB - After developing a map for certain states typical of hemopoietic stem cells (SCs), we identify a number of parameters (e.g. fractal dimensions, oscillatory behavior in a multistable landscape, etc.) that scale down to subcellular structures such as interphase genome, chromatids, chromatin entanglements and DNA segmental motions. A curious aspect is the continuous reappearance of recursive processes even at very small biologic scales. These iterations are relevant not only for the normal behavior of (hemopoietic) cells but also for amplifying hidden genomic singularities above some critical threshold. When that happens, there are sudden quali-quantitative and often clonal changes in the cell behavior. As illustrated by specific leukemic cases, many paradoxes of malignant growth seem best explained by the peculiar sensitivity to initial condition of (hemopoietic) cells. Interpreted as chaotic oscillators, these cells display a spectrum of disorders that, in spite of appearing as random, are in fact triggered by amplification of subtle preconditions with statistico-deterministic outcomes, that are predictable within certain time limits. PMID- 1865839 TI - The role of the saphenous nerve in insomnia: a proposed etiology of restless legs syndrome. AB - Entrapment of the saphenous nerve after emergence from its lumbar roots and before its distribution to the medial surface of the leg is suggested as a cause of Restless Legs Syndrome (other anomalies of the saphenous nerve, especially those where the nerve is part of a general neuropathy, are not considered here). This finding is supported by evidence which: 1) identifies Restless Legs Syndrome as a nerve entrapment syndrome from: the dysesthesia in Meralgia Paresthetica, the paraesthesiae of Carpal Tunnel Syndrome and the poorly localized pain in pronator syndrome and suprascapular nerve entrapment; 2) isolates the saphenous nerve as the entrapped nerve from the patient's difficulty in identifying the precise area of sensation in saphenous nerve entrapment at Hunter's Canal; 3) localizes the pelvic region as the site of entrapment from rates of Restless Legs Syndrome of 11 and 19% in pregnant women, a correlation between chronic nonspecific prostatitis and Restless Legs Syndrome. PMID- 1865840 TI - Kaposi's sarcoma among AIDS patients: transmissible venereal tumour by cell engraftment? AB - The epidemiologic findings of Kaposi's sarcoma (KS) among patients with the acquired immunodeficiency syndrome (AIDS) suggest that human immunodeficiency virus (HIV) infection is insufficient for the development of KS. It was speculated that another sexually transmitted infection is responsible for the markedly increased incidence of KS among patients who acquired HIV infection through sexual intercourse. However, no such contributing infectious agent was consistently identified. The canine transmissible venereal tumour (TVT) is a malignant tumour that can be transplanted by viable cells across major histocompatibility complex (MHC) barriers. Recent findings suggest that all canine TVTs originated from the same tumour and were transferred from one animal to the other during sexual intercourse. It is suggested that, in analogy with the canine TVT model, the characteristics of KS epidemic among AIDS patients may be explained by transmission and engraftment of viable malignant cells during intercourse. PMID- 1865841 TI - [The forensic medical assessment of occupational hypoacusis in the penal field]. AB - The authors discuss the difference between otopathy intended as anatomic and functional damage occurring in the Corti cells, and hearing loss intended purely as the functional aspect of otopathy. The different juridical interpretations of the "appreciability" concept are described, both case by case interpretation and interpretation on the basis of a minimal threshold limit (10-15%). In Italian penal law and jurisprudence, an extremely rigorous approach is generally used based on the minimum technically detectable impairment. A recent sentence of the Penal Court (No. 4049/89) is illustrated. Other juridical problems posed by Italian law and jurisprudence are reviewed and discussed. Practical operational problems are described and guidelines for intervention are proposed. The authors strongly support the need for a multidisciplinary approach to the problems of occupational hearing loss or impairment which is one of the chief aims of the Italian National Study Group for Forensic Audiology, which consists of members of the Italian scientific societies of Audiology, Occupational Medicine, and Forensic and Insurance Medicine. PMID- 1865842 TI - Mortality among male farmers licensed to use pesticides. AB - The mortality experience of 4,580 male farmers licensed to buy and use pesticides in Northern Italy was examined from 1974 to 1987. The historical cohort was determined from the registers of the agricultural inspectorate offices. The vital status at the end of the study period was ascertained by municipality records and only 4 subjects were lost to follow-up. Death certificates were obtained for 100% of the 565 identified deaths. External comparison on to the Italian male population was supplemented by regional comparison. Mortality deficits were observed for all causes, all neoplasms and most specific malignancies. A non significant mortality excess due to brain cancer, compared both to national and regional populations, was found (11 cases, Standardized Mortality Ratio 169 and 139, respectively). The excess of brain cancer became statistically significant in the age group 65-75 years. Caution must be used in the interpretation of our findings. Nevertheless, it seems reasonable to hypothesize an association of the observed excess of brain cancer with the occupational and/or environmental exposure of the cohort. PMID- 1865843 TI - [Impairment of the osteoarticular and musculoligamentous components in bill posters: an example of the thoracic outlet syndrome]. AB - The authors analysed the risks and associated damage in bill posters on the basis of a case history description. Biomechanical analysis of the job revealed in particular the involvement of the musculoligamentous structure of the cervical spine and shoulder, mostly during the actual posting of bills. The authors propose a clinical-functional definition of the pain and paresthetic symptoms of the upper limbs which are frequently encountered in this category of workers. PMID- 1865844 TI - Vibration effects on fatty acid composition of organ and cell membrane lipids. AB - The influence of middle and high frequency vibrations (50 and 150 Hz) on the fatty acid pattern of structural lipids in white rat liver, kidney, heart, aorta and muscular tissue was studied in a 3-month experiment. The study also examined the fatty acid composition of phospholipids in erythrocyte cell membranes of workers occupationally exposed to vibrations and of patients suffering from vibration disease. Statistically significant changes in the per cent distribution of fatty acids were observed, which were more evident in the liver and kidney of experimental animals, and also after high frequency (150 Hz) vibration exposure. Changes in human subjects were greater in workers exposed to hand-arm vibrations and in patients suffering from vibration disease. Routine and more precise methods are needed to assess occupational risk via determination of the lipid metabolism state in workers exposed to vibrations and in patients suffering from vibration disease. PMID- 1865845 TI - [Asbestosis in a truck driver: a clinical case and analysis of the exposure]. AB - The paper reports a case of asbestosis in a truck driver whose anamnesis, at first, revealed no evidence of previous exposure to asbestos, whether occupational or extra occupational. A pleuro-pulmonary fibrosis was discovered in 1987, following an episode of exudative pleurisy on the right side. The thickened pleura was then surgically removed. In the samples of pleuro-pulmonary fibroid tissue taken during the operation, typical asbestos bodies were demonstrated in optical microscopy. The analysis of possible exposure to asbestos that might not have been referred in the anamnesis revealed that in at least six widely used truck models (of which three were driven by the worker from 1958 to 1984), the presence of an asbestos winding around a manifold found on the bottom or on the side of the engine. In such trucks, the engine is inside the driver's cab, covered by a cowling set on the floor. Asbestos fibers could enter the driver's cab through a little window in the cowling or through outlets in the dashboard, carried by the airflow generated by the big fan at the back of the radiator and by the truck motion itself. The window or the outlets remained open during cold periods of the year to allow the air, warmed by the motor, to enter the driver's cab. PMID- 1865846 TI - [The use of 1,1,1-trichloroethane (methylchloroform) in industrial operations: the neurotoxicity risk]. AB - 1,1,1-Trichloroethane (1,1,1-TE) is a widely used organic solvent which is thought to be relatively safe. The present review is mainly focused on the neurotoxic effects of 1,1,1-TE. Concentrations above 350 ppm are considered capable of negatively conditioning the performance of the exposed person, in particular reaction time and manual abilities. Peripheral neuropathies have also been described. More recently the potential neurotoxicity of 1,1,1-TE has been underscored by animal studies investigating the effects of this substance in neurobehavioral tests and on neurochemical parameters. 1,1,1-TE alters the motor activity in small laboratory rodents. In fixed interval responding in mice, the effects of 1,1,1-TE are qualitatively similar to those of other volatile (ethanol) and non volatile (benzodiazepines and barbiturates) CNS depressants. In addition, in drug discrimination procedures 1,1,1-TE shares discriminative stimulus properties with barbiturates, toluene, halotane, and oxazepam indicating that this solvent has behavioral effects in common with central nervous system depressant drugs. From a neurochemical point of view long-term exposure to 1,1,1 TE induces astrogliosis in the cerebral cortex of gerbils as indicated by an increased concentration of glial fibrillary acidic protein. In addition low dose inhalation of 1,1,1-TE for 3 months decreases DNA concentrations in several brain regions of the gerbil. 1,1,1-TE affects also brain concentrations of cAMP and cGMP as well as calcium ion control, possibly through an action on voltage dependent calcium channels. It has been also suggested that intermediate metabolites of 1,1,1-TE may give origin to condensation products with dopamine, ultimately impairing dopaminergic transmission. Some of the neurochemical effects of 1,1,1-TE are shared by other chlorinated organic solvents as well as by CNS depressants. The literature analyzed indicates that 1,1,1-TE may exert significant neurotoxic effects suggesting that more caution in its use is needed and that attention should be paid to the possibility of an additive effect of 1,1,1-TE and CNS depressants (ethanol, barbiturates, benzodiazepines and other volatile solvents) giving origin to severe neurotoxicity. PMID- 1865847 TI - [Operator exposure levels in nuclear medicine studies]. AB - In diagnostic examinations performed in nuclear medicine, radio-isotopes with a relatively short half-life are used, the quantity varying according to the type of examination. After administration of the labelled substance, the patient becomes a large source of ionizing radiations. During the course of a scintigraphic examination, the operator is obliged to go near the couch to assist the patient in the positions and will therefore inevitably be in this radiation field. The paper reports the radio-activity levels recorded at gonad and eye levels of the operator in positions most frequently held during the course of the most commonly performed scintigraphic examinations using a G.E. STARCAM 500 A gamma-camera. PMID- 1865848 TI - [Bicycle ergometry exercise tests: a comparison between 3 protocols with an increasing load]. AB - A group of 26 male long-distance runners performed 3 cycle ergometer tests of progressively increasing intensity up to exhaustion. The tests were performed on 3 different days. The workload increased as follows: 30 Watts every 3 min (test I), 10 Watts every min (test II), and 30 Watts every min (test III). Ventilatory and gas exchange measurements were averaged every 30 sec during each test. The heart rate (HR) was monitored continuously by ECG. In each test the anaerobic threshold (AT) was determined using ventilatory and gas exchange indices (VE, VCO2, VE/VO2). The work load on exhaustion and power at AT were the same comparing test I with test II, but these values were significantly higher in the 30 Watts/1 minute test. Conversely, maximal oxygen uptake (VO2 max) and the VO2 observed at anaerobic threshold were comparable in the 3 protocols. The slopes of VO2, VCO2, VE and HR against the work load (Watts) were identical in test I and II, but were slower in test III. However, no differences in the ventilatory and heart rate patterns versus oxygen uptake were observed comparing the three exercise tests. These results suggest a good comparability between the 30 Watts/3 min test and the 10 Watt/1 min protocol. Furthermore, for workloads below AT, a steady state was attained at the 3rd minute of each phase during test I, while oxygen uptake and other cardio-respiratory variables were underestimated during the protocol in which phases of 30 Watts were maintained only for 1 minute.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865849 TI - [The admissibility into Italian regulations of the TLV. The paragraph on occupational carcinogens]. PMID- 1865850 TI - [A program for hearing preservation]. PMID- 1865851 TI - Topical drugs for vaginal candidiasis. PMID- 1865852 TI - Alglucerase for Gaucher's disease. PMID- 1865853 TI - Irritable bowel syndrome complaints following the uprising of December 1989 in Romania. AB - Irritable bowel syndrome has a strong psychogenic component. One of its features is the influence of stress on the clinical state. An increased amount of irritable-bowel-like symptoms within the first month following the uprising in Romania in December 1989 is reported. These symptoms seem to be related to the impressive amount of stress developed by dramatic events presented live on television and watched by the population. Several new cases as compared to the previous year were also reported by our group for the study of psychogenic factors in irritable bowel syndrome. PMID- 1865855 TI - Human and health rights of Palestinians in the Occupied Territories. Essay review. PMID- 1865854 TI - Doctors and human rights. AB - This article describes the roles of Amnesty International's Medical Groups and the Medical Foundation for the Care of Victims of Torture in campaigning for and treating those suffering the physical and psychological effects of human rights abuse in peace and war. PMID- 1865856 TI - 'Low intensity' war and mental trauma in Nicaragua: a study in a rural community. AB - 'Low intensity' warfare, with its key psychological element, aimed to terrorize the rural population of Nicaragua during the 1980s. A survey of ex-refugees still living in the war zone revealed 62% of men and 91% of women as 'cases' of psychological disturbance on the General Health Questionnaire. Somatization was central to the subjective experience and communication of the distress caused by the Contra war. Sustained sleep disturbance, hyperalertness and other anxiety based symptomatology and poor concentration were very common and were exacerbated by war-related cues. 25% of men and 50% of women merited a diagnosis of posttraumatic stress disorder. Some distress reflected unresolved grief states. The longer term mental and social costs of terrorization have been insufficiently documented in the Third World. PMID- 1865857 TI - Diagnosis: the Achilles' heel of biological psychiatry. PMID- 1865858 TI - Biomedical ethics: confronting dilemmas of modern medicine. PMID- 1865859 TI - Adolescent occupational injuries in Minnesota. A descriptive study. AB - A descriptive study of adolescent work injuries was undertaken using information from Minnesota Department of Labor and Industry workers' compensation files. During the two-year period, 1986-1987, 1,607 work-related injuries were reported in adolescents ages 12 through 17. The largest proportions of injuries occurred in wholesale and retail trade (61.2%), services (24.1%), and manufacturing (5.8%). Injuries most commonly reported were sprains (27.1%), lacerations (26.5%), heat burns (11.4%), and contusions (8.8%). Average annual injury rates were estimated at 14.0/1,000 full-time equivalents for adolescents compared with 24.5/1,000 for adults. The extent of disability or severity of injury could not be determined except that there were no deaths reported during this period. PMID- 1865860 TI - Diagnosis of meniscal and cruciate ligament tears using MRI. Evaluation of two scanning techniques. AB - The accurate diagnosis of meniscal and cruciate ligament tears is essential for proper management of knee injuries. In recent years, magnetic resonance imaging has been increasingly used to diagnose knee pathology. Several articles have documented the accuracy of MRI, but conflicting results have been reported. We present a series of 50 consecutive patients who underwent both MRI and complete arthroscopy. We tested two different scanning protocols and found the higher resolution scanning protocol to be more accurate, resulting in fewer discrepancies between the results of MRI and arthroscopy, which we used as the standard for comparing the MRI interpretations. Magnetic resonance imaging is an important diagnostic tool in orthopedic practice. It is available, accurate, and well-accepted by patients. However, as demonstrated by the results of this study, the accuracy of MRI is highly dependent upon the scanning protocol used. PMID- 1865861 TI - Communicating DNR orders to ambulance personnel. AB - To summarize, the MMA will provide a standard DNR form and guidelines for implementation in local communities. Local physicians, nursing home administrators, and ambulance service operators need to agree on an established set of guidelines that long-term care facilities, hospices, and private homes will follow to inform ambulance personnel of DNR orders. Ambulance medical directors should instruct ambulance staff on the proper implementation and use of DNR orders. The decision to write a DNR order rests with the attending physician, based on disclosure and consent of the patient, family, or proxies. Full implementation of a prehospital DNR system will reduce the suffering that patients and family members endure when inappropriate and unnecessary cardiopulmonary resuscitation is given by ambulance personnel. A similar program, administered by the county health department, has been successful in the west metropolitan Twin Cities area for the past five years. The model offered by the MMA to individual physicians and their medical societies may be modified to meet local needs. This community emergency medical services DNR program helps ensure the provision of appropriate ambulance service based on patients' individual needs and requests. PMID- 1865862 TI - Futures in your future. PMID- 1865863 TI - Judge favors patient notification. PMID- 1865864 TI - Oregon sets AIDS policy. PMID- 1865865 TI - In the aftermath: health care in Kuwait city. PMID- 1865866 TI - Sisters share their lives. Interview by Sharon White. PMID- 1865867 TI - Nursing management information system development. PMID- 1865868 TI - Mississippi becoming a leader in advancing work place advocacy. PMID- 1865869 TI - Workplace advocacy new watchword. PMID- 1865870 TI - A survey of Mississippi nurses' knowledge of AIDS. PMID- 1865871 TI - Childhood cancers--New Jersey, 1979-1985. AB - In New Jersey, cancers among children aged 0-14 years account for fewer than 1% of all cancers diagnosed annually; however, childhood cancers account for the greatest number of years of potential life lost from cancer. This report summarizes a study by the New Jersey State Department of Health (NJSDH) that determined the incidence and death rates for the most frequent cancers among children aged 0-14 years in New Jersey during 1979-1985; these rates are compared with those for the United States for a comparable period. PMID- 1865872 TI - Comparative mortality of two college groups, 1945-1983. AB - Patterns of morbidity and mortality vary substantially among some religious groups in the United States. These variations may be associated with a wide range of factors, including lifestyle, acceptance of prevention measures (e.g., vaccination), and risks for injury (1-12). This report summarizes a study of mortality in cohorts of graduates from two colleges whose students are from different religious backgrounds. PMID- 1865873 TI - Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures. Recommendations of the Immunization Practices Advisory committee (ACIP). AB - This revision of the Immunization Practices Advisory Committee (ACIP) statement on diphtheria, tetanus, and pertussis updates the statement issued in 1985, and incorporates the 1987 supplementary statement, which addressed two issues: a) the risks and benefits of pertussis vaccine for infants and children with family histories of convulsions; and b) antipyretic use in conjunction with diphtheria and tetanus toxoids and pertussis vaccine absorbed (DTP) vaccination among children with personal or family histories of convulsions (1,2). This document presents new recommendations for epidemiologic investigation and management of contacts of diphtheria patients. The updated recommendations include a review of the epidemiology of the three diseases and descriptions of the available immunobiologic preparations with appropriate vaccination schedules. Also included are a) new information on and reassessment of the possible relation between receipt of DTP and the occurrence of serious acute neurologic illness and permanent brain damage, b) revisions in the recommendations on precautions for and contraindications to pertussis vaccine use, and c) revisions on recommendations for chemoprophylaxis for household and other close contacts of pertussis patients. The Committee has reviewed and taken into consideration the recent report by the Institute of Medicine entitled, "Adverse Effects of Pertussis and Rubella Vaccines" in making these recommendations. PMID- 1865874 TI - Transcription of the Petunia mitochondrial CMS-associated Pcf locus in male sterile and fertility-restored lines. AB - Transcripts of the Petunia mitochondrial cytoplasmic male sterility (CMS) associated S-Pcf locus, which consists of three co-transcribed genes (pcf, NADH dehydrogenase subunit 3, and ribosomal protein S12), have been characterized in reproductive tissues of CMS and fertility restored (Rf) Petunia lines by nuclease protection experiments and by RNA blot hybridization. Three 5' transcript termini have been previously described. Two 3' transcript termini and an additional S-Pcf locus transcript have now been identified. The relative abundance of the three 5' transcript termini is influenced by the presence of the nuclear Rf gene. A decrease in the abundance of the -121 5' transcript terminus relative to the -266 and -522 termini is consistently seen in Petunia lines which are restored to fertility by the Rf gene, compared to CMS Petunia lines. An additional transcript with a 5' terminus within the urf-s region of pcf is much more abundant in immature bud and anther tissue than in leaf or suspension cells. The total abundance of pcf transcripts varies greatly between plants of different nuclear backgrounds which lack the nuclear Rf allele, indicating that other nuclear genes also influence expression of the S-Pcf locus. PMID- 1865875 TI - Correlation of biochemical blocks and genetic lesions in leucine auxotrophic strains of the imperfect yeast Candida maltosa. AB - The four enzymatic steps in the conversion of alpha-ketoisovaleriate to leucine were examined in the wild type and in 13 leucine auxotrophic strains of Candida maltosa. The genetic lesions in the auxotrophs, involve at least five different loci and are correlated with three enzymatic steps. This was confirmed by gene cloning, protoplast fusion, and enzyme assays. The pathway for leucine biosynthesis in C. maltosa shows general similarity to that of other lower eukaryotes but there are individual differences in the numbers of genes responsible for single enzymatic steps. A disomic state of the chromosomes carrying genes coding for alpha-isopropylmalate synthase and beta-isopropyl malate dehydrogenase was elucidated. PMID- 1865876 TI - An auxin-auxotrophic mutant of Nicotiana plumbaginifolia. AB - Auxin (indole-3-acetic acid) is considered to be an important signalling molecule in the regulation of plant growth and development but neither auxin synthesis nor its mode of action is clearly understood. To identify genes involved in these processes, mutations were sought that altered the auxin requirement of plant tissues for growth. For the first time mutant plants were obtained that carry a recessive mutation at a single nuclear locus (aux1) which results in an absolute requirement for exogenous auxin for normal growth. In the absence of auxin treatment, mutant plants undergo premature senescence and die. PMID- 1865877 TI - The use of subtractive hybridization to obtain a DNA probe specific for Pseudomonas solanacearum race 3. AB - Pseudomonas solanacearum, the causal agent of bacterial wilt, has been classified into three races based on host range and into five biovars based on physiological properties. Strains of race 3 belong exclusively to biovar 2 and primarily affect potatoes. Although this race is thought to have originated in the Andean highlands, it has unusual physiological properties that make it a potential threat to potatoes grown at the cooler latitudes worldwide. Consequently, there is need for a rapid and sensitive method for detection of race 3 strains. We have used subtractive hybridization to enrich for race 3-specific DNA sequences in total race 3 genomic DNA, and thereby obtained a 2 kb clone homologous to DNA from all 28 race 3 strains tested, but with only five of 90 non-race 3 strains. In addition, two larger regions of the genome, containing a minimum of 23 kb of DNA, are also specific for race 3. Deletion of this DNA did not affect virulence. This race 3-specific DNA is a potentially useful diagnostic tool for the detection of race 3 strains. PMID- 1865878 TI - Analysis of barley nitrate reductase cDNA and genomic clones. AB - Barley nitrate reductase cDNA and genomic clones were isolated by homology with the barley nitrate reductase cDNA clone bNRp10 and sequenced. This is the first reported analysis of a full-length nitrate reductase gene and its corresponding cDNA in the same species. The longest cDNA clone extends to within 9 bp of the ATG start codon and the sequence is similar to that reported for the higher plant NR sequences. As expected, the amino acid sequence of barley nitrate reductase is more related closely to the rice (84% homology) than to the Arabidopsis (62%) sequence. Four different polyA addition sites were identified from sequence analysis of nine barley NR cDNA clones. A 7.3 kb region of a genomic recombinant lambda clone was subcloned as two contiguous BamHI fragments into p Bluescript, designated pMJ7 and pMJ8, and sequenced. These clones include the entire nitrate reductase coding region, one large intron, 2.7 kb of untranslated sequence 5' to the translation start codon and 0.25 kb 3' to the translation termination codon. The mRNA cap site was identified as a cytosine, 111 bases upstream of the ATG translation start codon. The putative CAAT and TATA boxes were identified at -115 and -33 bp, respectively, with the mRNA cap site designated as +1. The barley nitrate reductase gene coding region strongly favors G or C in the third codon position. PMID- 1865879 TI - Analysis of yeast prp20 mutations and functional complementation by the human homologue RCC1, a protein involved in the control of chromosome condensation. AB - Mutations in the PRP20 gene of yeast show a pleiotropic phenotype, in which both mRNA metabolism and nuclear structure are affected. srm1 mutants, defective in the same gene, influence the signal transduction pathway for the pheromone response. The yeast PRP20/SRM1 protein is highly homologous to the RCC1 protein of man, hamster and frog. In mammalian cells, this protein is a negative regulator for initiation of chromosome condensation. We report the analysis of two, independently isolated, recessive temperature-sensitive prp20 mutants. They have identical G to A transitions, leading to the alteration of a highly conserved glycine residue to glutamic acid. By immunofluorescence microscopy the PRP20 protein was localized in the nucleus. Expression of the RCC1 protein can complement the temperature-sensitive phenotype of prp20 mutants, demonstrating the functional similarity of the yeast and mammalian proteins. PMID- 1865882 TI - Determination and occurrence of benzo[a]pyrene in smoked meat products. PMID- 1865881 TI - The Escherichia coli recA gene increases resistance of the yeast Saccharomyces cerevisiae to ionizing and ultraviolet radiation. AB - The Escherichia coli recA protein coding region was ligated into an extrachromosomally replicating yeast expression vector downstream of the yeast alcohol dehydrogenase promoter region to produce plasmid pADHrecA. Transformation of the wild-type yeast strains YNN-27 and 7799-4B, as well as the recombination deficient rad52-1 C5-6 mutant, with this shuttle plasmid resulted in the expression of the bacterial 38 kDa RecA protein in exponential phase cells. The wild-type YNN27 and 7799-4B transformants expressing the bacterial recA gene showed increased resistance to the toxic effects of both ionizing and ultraviolet radiation. RecA moderately stimulated the UV-induced mutagenic response of 7799 4B cells. Transformation of the rad52-1 mutant with plasmid pADHrecA did not result in the complementation of sensitivity to ionizing radiation. Thus, the RecA protein endows the yeast cells with additional activities, which were shown to be error-prone and dependent on the RAD52 gene. PMID- 1865883 TI - [The determination of thiazafluron in drinking water]. PMID- 1865880 TI - CDC7 protein kinase activity is required for mitosis and meiosis in Saccharomyces cerevisiae. AB - The product of the CDC7 gene of Saccharomyces cerevisiae has multiple cellular functions, being needed for the initiation of DNA synthesis during mitosis as well as for synaptonemal complex formation and commitment to recombination during meiosis. The CDC7 protein has protein kinase activity and contains the conserved residues characteristic of the protein kinase catalytic domain. To determine which of the cellular functions of CDC7 require this protein kinase activity, we have mutated some of the conserved residues within the CDC7 catalytic domain and have examined the ability of the mutant proteins to support mitosis and meiosis. The results indicate that the protein kinase activity of the CDC7 gene product is essential for its function in both mitosis and meiosis and that this activity is potentially regulated by phosphorylation of the CDC7 protein. PMID- 1865884 TI - [Diaplacental transition of selected fatty acids in the rat]. PMID- 1865885 TI - Determination of antimony in drinking waters by an inexpensive, reproducible hydride generator for atomic spectroscopy. AB - A method for determining antimony in drinking waters is described. In order to prevent a substantial error caused by the different oxidation states of antimony, Sb(V) is reduced to Sb(III) with potassium iodide-ascorbic acid. Covalent hydride is generated with a home made device by adding NaBH4. The hydride is then atomized in a flame-heated silica tube and atomic absorption is measured spectrophotometrically. The optimal conditions for this determination are discussed and interference effects are described. Results obtained by determining linearity range (0-200 ng), detection (LOD) and quantitation (LOQ) limits (LOD = 0.347 ng/ml, LOQ = 1.158 ng/ml), precision (instrumental CV 4.08% and method CV 7.74%) and accuracy performed by recovery assays (96.1%) show that the method is useful for antimony determination at the concentration usually present in drinking water. PMID- 1865886 TI - Effect of fat and retinol loading on serum triglyceride and retinol levels in patients with ulcerative colitis. AB - Serum copper, zinc, selenium, magnesium, calcium, cholesterol, triglyceride and retinol contents were determined in 11 patients with ulcerative colitis and in 20 healthy volunteers. Lipid and retinol loadings were performed as well. No differences were found in serum copper, zinc, calcium and selenium levels between the groups. Serum magnesium levels were somewhat lower in the patients than in the volunteers. During the period of loading, cholesterol levels did not differ between the two groups at any time. Triglyceride levels except for two persons, were higher in patients. Triglyceride curves showed pathological courses in each case. Retinol concentrations in patients remained below the values observed in volunteers. Data suggest a disturbed utilization of fat and retinol in patients with ulcerative colitis. PMID- 1865887 TI - Accumulation of diflubenzuron in bolti fish Orechromis niloticus. AB - Orechromis niloticus fingerlings were exposed to the insect growth inhibitor diflubenzuron 1-(2,6-Difluorobenzoyl)3-(4-chlorophenyl)urea for 21 days. Diflubenzuron was introduced to the aquariums where fish were maintained at the beginning of the experiment, then its level in water, gills and liver was detected after 1, 7, 14 and 21 days. The fish accumulated diflubenzuron 76 and 99 times greater than the water content when kept in an ambient concentration of 2.5 and 5 mg/l, respectively, indicating a low bioaccumulation potential. Some degradation products of diflubenzuron were found mainly in liver and water. PMID- 1865888 TI - Microbiological status of Egyptian prawn. AB - A total of 110 prawn individuals were collected from different markets at Cairo and Giza Governorates. The average counts of Aerobes, Psychrophiles, Enterobacteriaceae, Coliforms and Staphylococci were 5 x 10(3), 3 x 10(2), less than 2 x 10(2), less than 3 and 2 x 10(2) organisms per gram newly caught prawn sample, respectively. Such counts were significantly increased in samples collected from markets including raw prawn in shell, raw peeled samples and frozen samples either peeled or in shell. Arizona group, Escherichia coli, Enterobacter group, Proteus group, Providencia group A & B, Shigella group and Staphylococcus aureus could be isolated from examined samples with variable percentages. The public health significance of isolated organisms is discussed. PMID- 1865889 TI - Effect of temperature on initial bacteria of prawn. AB - This study was carried out to evaluate the effect of heat and cold on the microorganisms existing in prawn. Roasting for 5 min, boiling for 10 min and storage at -18 degrees C for 10, 20 and 30 days were applied on raw prawn to study the effect of each treatment on the bacterial load. The average counts of APC (aerobic plate count) at 25 degrees C and 0 degree C, Enterobacteriaceae, Coliforms and Staphylococci were 1.3 x 10(7), 6 x 10(4), 2 x 10(2) and 3 x 10(3) organisms per gram raw prawn sample, respectively, then reduced to 10(4), 8 x 10(2), 3 x 10(3), less than 3 and 3 x 10(2) organisms per gram roasted prawn in shell, respectively. Such counts were more reduced in roasted peeled samples. Boiling reduced the average counts of APC at 25 degrees C and 0 degrees C, Enterobacteriaceae, Coliforms and Staphylococci from 8 x 10(8), 2 x 10(5) 2 x 10(7), 3 x 10 and 3 x 10(4) organisms per gram raw prawn sample to 2 x 10(5), 3 x 10(3), 2 x 10(2), less than 3 and 4 x 10(2) organisms, respectively. Concerning freezing storage, it could be observed that the average counts of APC at 25 degrees C and 0 degree C, Enterobacteriaceae, Coliforms and Staphylococci were reduced from 4 x 10(7), 5 x 10(5), 3 x 10(5), 10(3) and 3 x 10(2) organisms per gram raw sample to 5 x 10(4), 10(3), 3 x 10(2), 10 and less than 2 x 10(2) organisms per gram after freezing storage for 30 days. PMID- 1865890 TI - Effect of cumin, cinnamon, ginger, mustard and tamarind in induced hypercholesterolemic rats. AB - The effect of a few common spices--cumin (Cuminum cyminum, cinnamon (Cinnamomum zeylanicum), ginger (Zingiber officinale), mustard (Brassica nigra) and tamarind (Tamarindus indica)--added to normal and hypercholesterolemia inducing diet on serum and liver cholesterol levels in rats was studied. These spices did not show any cholesterol lowering effect when included in the diet at about 5-fold the normal human intake level. PMID- 1865891 TI - [The characterization of microbial lipases. 2. The determination of lipase specificity]. AB - Types of lipase specificity are as follows: Positional specificity; fatty acid specificity; stereospecificity; substrate specificity (different rates of lipolysis of different glyceride classes. The acylglycerol used for determination of lipase specificity must be so structured, that specificities are not confused and unambiguous results are obtained. Different substrates and methods for detection of specificity are reviewed and advantages and disadvantages are discussed. Positional specificity can be determined with synthetic dialkylacylglycerols and 2,3-dioleoyl butanediol. Stereospecificity can be detected with enantiomeric dialkylacylglycerols or diacylalkylglycerols. PMID- 1865892 TI - Some pathological and biochemical studies on experimental ascaridiasis in chickens. AB - During studying the pathogenicity of Ascaridia galli for young Ross-Broiler chickens fed with single doses of 100, 200 and 500 infective eggs, it was found that the infected chickens showed variable decreases in body weight gain and increases in the ratio of liver weight relative to body weight when compared with the control. Both decrease and increase was proportionally related with the number of infective eggs given to the chickens. Biochemical analysis of muscle and liver tissue of the previous groups of chickens showed a decrease in both glycogen and protein content and an increase in fat content of muscle and liver of infected chickens when compared with those of normal tissues. The decrease in the glycogen content due to ascaridiasis was mostly apparent in case of 500 egg dose and that of the protein content was noted with the egg doses of 200 and 500. Each of the three egg doses showed a significant increase in the fat content of the muscle and liver of infected chickens when compared with the control. After the sixth week of infection chickens fed with 500 eggs showed emaciation, loss of colour of combs and legs and of brightness of plumage, diarrhoea, drooping wings, ruffled feathers and a gradual loss of strength manifested by leg weakness. At autopsy, the small intestine showed external macroscopic lesions of haemorrhage and congestion. Intestinal obstruction with adult Ascaridia galli was also found in the infected birds. PMID- 1865893 TI - Dr Healy, Dr Kennedy and Mr Dingell. PMID- 1865894 TI - Stanford counts cost of overhead scandal. PMID- 1865895 TI - National Institutes of Health. Healy and Dingell lock horns. PMID- 1865896 TI - US National Laboratories. California's record attacked. PMID- 1865897 TI - Animal rights. A leap into controversy. PMID- 1865898 TI - Biomedical research. New institute snares prize team. PMID- 1865899 TI - Animal rights. PMID- 1865900 TI - Bad taste. PMID- 1865901 TI - Towards the brain-computer's code? PMID- 1865902 TI - Cell biology. ABG of microtubule assembly. PMID- 1865903 TI - Structural biology. Complex behaviour. PMID- 1865904 TI - Whaling in the dark. PMID- 1865905 TI - Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. AB - Two crystal structures of the glucocorticoid receptor DNA-binding domain complexed with DNA are reported. The domain has a globular fold which contains two Zn-nucleated substructures of distinct conformation and function. When it binds DNA, the domain dimerizes, placing the subunits in adjacent major grooves. In one complex, the DNA has the symmetrical consensus target sequence; in the second, the central spacing between the target's half-sites is larger by one base pair. This results in one subunit interacting specifically with the consensus target half-site and the other nonspecifically with a noncognate element. The DNA induced dimer fixes the separation of the subunits' recognition surfaces so that the spacing between the half-sites becomes a critical feature of the target sequence's identity. PMID- 1865906 TI - Effects of a change in the level of inbreeding on the genetic load. AB - "The effects of inbreeding may not be as noticeable in the first generation as the invigoration immediately apparent after crossing". This statement, published in 1919, has received little attention, and has apparently never been tested empirically, although the reduction of the genetic load of populations by inbreeding is well known in theoretical terms. Because inbreeding increases homozygosity, and hence the effectiveness of selection against recessive or partially recessive detrimental alleles, changes in levels of inbreeding can lead to a reduction in the frequencies of such mutant alleles. This results in equilibration at higher population mean fitness and is referred to as 'purging' populations of their genetic load. Severe inbreeding can also reduce genetic load due to overdominant alleles, provided selection coefficients are not symmetrical at all loci, because alleles giving lower fitness will be reduced in frequency at equilibrium. With either fitness model, however, reduction in genetic load takes time, and the initial effect of an increase in inbreeding is reduced fitness due to homozygosity. There are few data relating to the extent to which fitness is reduced during inbreeding in a set of lines and to how long the reduction lasts before increasing again to the initial level, or higher. Inbreeding experiments involving sib mating in mice and Drosophila subobscura, and successive bottlenecks in house flies have yielded some evidence consistent with the purging hypothesis. Here, we report results of an experiment demonstrating a prolonged time-course of recovery of mean fitness under self-fertilization of a naturally outcrossing plant, and also compare our results with expectations derived by computer calculations. Our results show that the genetic load present in an outcrossing population can be explained only with a high mutation rate to partially recessive deleterious alleles, and that inbreeding purges the population of mutant alleles. PMID- 1865907 TI - Transgenic plant aequorin reports the effects of touch and cold-shock and elicitors on cytoplasmic calcium. AB - Methods for measuring plant cytoplasmic calcium using microelectrodes or microinjected fluorescent dyes are associated with extensive technical problems, so measurements have been limited to single or small groups of cells in tissue strips or protoplasts. Aequorin is a calcium-sensitive luminescent protein from the coelenterate Aequorea victoria (A. forskalea) which is formed from apoaequorin, a polypeptide of relative molecular mass approximately 22,000, and coelenterazine, a hydrophobic luminophore. Microinjected aequorin has been widely used for intracellular calcium measurement in animal cells, but its use in plants has been limited to exceptionally large cells. We show here that aequorin can be reconstituted in transformed plants and that it reports calcium changes induced by touch, cold-shock and fungal elicitors. Reconstituted aequorin is cytoplasmic and nonperturbing; measurements can be made on whole plants and a calcium indicator can be constituted in every viable cell. Now that apoaequorin can be targeted to specific organelles, cells and tissues, with the range of coelenterazines with differing calcium sensitivities and properties available, this new method could be valuable for determining the role of calcium in intracellular signalling processes in plants. PMID- 1865908 TI - The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy. AB - Although murine X-linked muscular dystrophy (mdx) and Duchenne muscular dystrophy (DMD) are genetically homologous and both characterized by a complete absence of dystrophin, the limb muscles of adult mdx mice suffer neither the detectable weakness nor the progressive degeneration that are features of DMD. Here we show that the mdx mouse diaphragm exhibits a pattern of degeneration, fibrosis and severe functional deficit comparable to that of DMD limb muscle, although adult mice show no overt respiratory impairment. Progressive functional changes include reductions in strength (to 13.5% of control by two years of age), elasticity, twitch speed and fibre length. The collagen density rises to at least seven times that of control diaphragm and ten times that of mdx hind-limb muscle. By 1.5 years of age, similar but less severe histological changes emerge in the accessory muscles of respiration. On the basis of these findings, we propose that dystrophin deficiency alters the threshold for work-induced injury. Our data provide a quantitative framework for studying the pathogenesis of dystrophy and extend the application of the mdx mouse as an animal model. PMID- 1865909 TI - Amino-terminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product. AB - The proteins encoded by the myc gene family are involved in the control of cell proliferation and differentiation, and aberrant expression of myc proteins has been implicated in the genesis of a variety of neoplasms. In the carboxyl terminus, myc proteins have two domains that encode a basic domain/helix-loop helix and a leucine zipper motif, respectively. These motifs are involved both in DNA binding and in protein dimerization. In addition, myc protein family members share several regions of highly conserved amino acids in their amino termini that are essential for transformation. We report here that an N-terminal domain present in both the c-myc and N-myc proteins mediates binding to the retinoblastoma gene product, pRb. We show that the human papilloma virus E7 protein competes with c-myc for binding to pRb, indicating that these proteins share overlapping binding sites on pRb. Furthermore, a mutant Rb protein from a human tumour cell line that carried a 35-amino-acid deletion in its C terminus failed to bind to c-myc. Our results suggest that c-myc and pRb cooperate through direct binding to control cell proliferation. PMID- 1865910 TI - Preferential DNA secondary structure mutagenesis in the lagging strand of replication in E. coli. AB - When present in single-stranded DNA, palindromic or quasi-palindromic sequences have the potential to form complex secondary structures, including hairpins, which may facilitate interstrand misalignment of direct repeats and be responsible for diverse types of replication-based mutations, including deletions, additions, frameshifts and duplications. In regions of palindromic symmetry, specific deletion events may involve the formation of a hairpin or other DNA secondary structures which can stabilize the misalignment of direct repeats. One model suggests that these deletions occur during DNA replication by slippage of the template strand and misalignment with the progeny strand. The concurrent DNA replication model, involving an asymmetric dimeric DNA polymerase III complex which replicates the leading and lagging strands, has significant implications for mutagenesis. The intermittent looping of the lagging strand template, and the fact that the lagging strand template may contain a region of single-stranded DNA the length of an Okazaki fragment, provides an opportunity for DNA secondary-structure formation and misalignment. Here we report our design of a palindromic fragment to create an 'asymmetric palindromic insert' in the chloramphenicol acetyltransferase gene of plasmid pBR325. The frequency with which the insert was deleted in Escherichia coli depends on the orientation of the gene in the plasmid. Our results suggest that replication-dependent deletion between direct repeats may occur preferentially in the lagging strand. PMID- 1865911 TI - Solid-phase gene assembly. AB - New technologies for multiple chemical synthesis of oligonucleotides and stepwise hybridization on a solid-phase support enable the rapid and cost-effective preparation of long duplex DNA regions. Will these new technologies usher in a new era in protein engineering? PMID- 1865912 TI - Final Exit: euthanasia guide sells out. PMID- 1865913 TI - AIDS. Leaked report queries Gallo patent. PMID- 1865915 TI - US biomedical research. Exploring the limits to continued growth. PMID- 1865914 TI - French scientists rebel against review system. PMID- 1865916 TI - Less animal testing. PMID- 1865917 TI - Imanishi-Kari (continued). PMID- 1865918 TI - NIH need clear definition of fraud. PMID- 1865919 TI - Immunology. Disease and evolution. PMID- 1865920 TI - Population genetics. A way to world knowledge. PMID- 1865921 TI - Riddle of the giant panda. PMID- 1865922 TI - The spread of HIV-1 in Africa: sexual contact patterns and the predicted demographic impact of AIDS. AB - The spread of HIV-1 in Africa is examined here in the light of recent information on the main epidemiological and behavioural determinants of transmission. Mathematical models incorporating demographic, epidemiological and behavioural processes are used to assess the potential demographic impact of the disease AIDS. These analyses highlight the significance of patterns of sexual behaviour, and in particular networks of sexual contact, on the predicted spread of infection. Current data reveal substantial variations in the degree of spread between and in countries, but new analyses support earlier predictions that in the worst-afflicted areas AIDS is likely to change population growth rates from positive to negative values in a few decades. PMID- 1865923 TI - Common west African HLA antigens are associated with protection from severe malaria. AB - A large case-control study of malaria in West African children shows that a human leucocyte class I antigen (HLA-Bw53) and an HLA class II haplotype (DRB1*1302 DQB1*0501), common in West Africans but rare in other racial groups, are independently associated with protection from severe malaria. In this population they account for as great a reduction in disease incidence as the sickle-cell haemoglobin variant. These data support the hypothesis that the extraordinary polymorphism of major histocompatibility complex genes has evolved primarily through natural selection by infectious pathogens. PMID- 1865924 TI - Mating patterns in seminatural populations of mice influenced by MHC genotype. AB - Because of the central role of major histocompatibility complex (MHC) genes in immune recognition, it is often assumed that parasite-driven selection maintains the unprecendented genetic diversity of these genes. But associations between MHC genotype and specific infectious diseases have been difficult to identify with a few exceptions such as Marek's disease and malaria. Alternatively, MHC-related reproductive mechanisms such as selective abortion and mating preferences could be responsible for the diversity. To determine both the nature and strength of selection operating on MHC genes by we have studied components of selection in seminatural populations of mice (Mus musculus domesticus). Here we assess MHC related patterns of reproduction and early (preweaning) mortality by analysing 1,139 progeny born in nine populations, and 662 progeny from laboratory matings. Reproductive mechanisms, primarily mating preferences, result in 27% fewer MHC homozygous offspring than expected from random mating. MHC genotype had no detectable influence on neonatal (preweaning) mortality. These mating preferences are strong enough to account for most of the MHC genetic diversity found in natural populations of Mus. PMID- 1865925 TI - 'Pseudo' domains in phage-encoded DNA methyltransferases. AB - 5-Cytosine-DNA-methyltransferases, which are found in many organisms ranging from bacteriophages to mammals, transfer a methyl group from S-adenosylmethionine to the carbon-5 of a cytosine residue in specific DNA target sequences. Some phage encoded methyltransferases methylate more than one sequence: these enzymes contain several independent target-recognizing domains each responsible for recognizing a different site. The amino-acid sequences of these multispecific methyltransferases reveal that some enzymes in addition carry domains that do not contribute to the enzymes' methylation potential, but strongly resemble previously identified target-recognizing domains. Here we show that introducing defined amino-acid alterations into these inactive domains endows these enzymes with additional methylation specificities. Gel retardation analysis demonstrates that these novel methylation specificities correlate with the acquisition of additional DNA-binding potential of the proteins. PMID- 1865926 TI - Bioaccumulation, elimination and metabolism of triphenyltin chloride by early life stages of minnows Phoxinus phoxinus. PMID- 1865927 TI - Neurodepressing effect of brassinosteroids in the cockroach Periplaneta americana. PMID- 1865928 TI - Positive cooperative interaction of quaternary anticholinergics with functional muscarinic receptors in bovine tracheal smooth muscle. AB - The interaction of quaternary anticholinergics with muscarinic receptors in bovine tracheal smooth muscle strips was investigated because some of these compounds have shown anomalous (biphasic) behaviour in radioligand displacement studies, in contrast to their tertiary analogues. It was found that ipratropium, N-methylscopolamine, oxyphenonium and N-methyldeptropine give Schild plots with slopes significantly greater than unity (up to 2.0) in contrast to 4-DAMP methobromide and thiazinamium, and the tertiary analogues atropine and scopolamine. However, in guinea pig tracheal smooth muscle, ipratropium and N methyldeptropine behaved as classic antagonists with Schild slopes of unity. The high Schild plot slopes in bovine tracheal smooth muscle could not be solely explained by inadequate equilibration of the antagonists, since increased incubation times (3 or 5 h instead of 30 min) still brought about slopes significantly greater than unity, or by the presence of an atropinesterase in the tissue. However, by using combinations of atropine with ipratropium or oxyphenonium it could be demonstrated that these quaternary antagonists interact with muscarinic M3 receptors in bovine but not in guinea pig tracheal smooth muscle in a positive cooperative fashion. PMID- 1865929 TI - Does brain histamine contribute to the development of hypertension in spontaneously hypertensive rats? AB - Histaminergic neurons of the brain have been implicated in genetic hypertension. We investigated the effect of inhibition of histamine synthesis by alpha fluoromethylhistidine (alpha-FMH), the irreversible inhibitor of histidine decarboxylase, on the development and maintenance of hypertension in spontaneously hypertensive rats. Young (3-week-old) and adult (7-week-old) rats were treated with alpha-fluoromethylhistidine for 29 and 13 days, respectively. Treatment of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats with alpha-fluoromethylhistidine led to a pronounced decrease in the histidine decarboxylase activity and in the histamine concentration in the brain (hypothalamus, brainstem, cortex-midbrain). In adult spontaneously hypertensive rats, the development of hypertension was not influenced by alpha fluoromethylhistidine. In young spontaneously hypertensive rats, alpha fluoromethylhistidine led to a transient delay in the development of hypertension which was followed by a transient tendency to increased blood pressure. It is concluded that histaminergic neurons of the brain play only a subordinate role, if any at all, in the development of hypertension in spontaneously hypertensive rats. PMID- 1865930 TI - Flow-dependent extraction of 1-naphthol by the rat isolated perfused kidney. AB - The influence of variation of perfusion flow rate on the renal clearance of p aminohippuric acid and 1-naphthol was studied with an isolated perfused rat kidney preparation. Kidney functions were well maintained at low perfusion flow rates by the use of a fluorocarbon emulsion to increase the oxygen capacity of the perfusion buffer. Renal extraction of p-aminohippuric acid decreased with increasing perfusion flow. Our data show that at high perfusion flow rates maximal extractable perfusion flow forms only a small part of the total perfusion flow. 1-Naphthol is rapidly metabolized to its glucuronide and sulfate conjugate in the isolated perfused rat kidney. Using PAH as a marker for the maximal extractable perfusion flow, 1-naphthol could be regarded as a high-extraction compound even at high perfusion flow rates. Our results suggest that p aminohippuric acid clearance, rather than total perfusion flow rate, should be used as the measure of maximal extractable blood flow for the estimation of extraction ratio in the isolated perfused kidney of compounds excreted or metabolized by the proximal tubules. PMID- 1865931 TI - [Diagnosis of neoformations in the colon; radiography or illumination?]. PMID- 1865932 TI - [Emergency situations in patients in psychiatric hospitals; confusing and ambiguous statement of the Medical Inspection for Public Mental Health]. PMID- 1865933 TI - [Human T-cell lymphotropic virus Type I (HTLV-I) as a cause of progressive myelopathy]. PMID- 1865934 TI - [Voice rehabilitation following larynx extirpation using the Groningen button]. AB - The long term results of implantation of the 'Groningen button' after total laryngectomy were determined retrospectively in the ENT Department of the University Hospital Groningen, after follow-up periods of 6 months to 5 years. The study group consisted of 86 patients who received a Groningen button between 1981 and 1985, 79 men and 7 women with an average age of 60.5 years at the time of the total laryngectomy. The Groningen button is a silicon valve, which is introduced into a tracheo-oesophageal shunt, thus preventing aspiration of oesophageal contents and keeping the shunt open. The valve can be placed primarily during the laryngectomy or secondarily after the laryngectomy. The results of the voice restoration with the Groningen button were better than the results achieved with the injection oesophageal speech only. The results of a primarily constructed shunt with placement of the button were better than those of a button placed secondarily more than one year after the laryngectomy. The average lifetime of a button was about 3 months. The buttons of one-third of all patients were removed permanently after some time. In our study the complications were few. In our opinion a Groningen button can be placed during a laryngectomy to achieve a better voice restoration. PMID- 1865935 TI - [Balloon embolization of a large carotid-cavernous fistula]. AB - A 58-year-old male patient with a giant carotid-cavernous fistula was treated by means of endovascular balloon embolisation. The fistula was closed, and good antegrade flow in the carotid artery and intracranial vessels was obtained. Based on this case history, the pathophysiology, ultrasonographic and angiographic evaluation and treatment options are reviewed. PMID- 1865936 TI - [Immunotoxicology; current developments and perspectives]. PMID- 1865937 TI - [Classification and treatment of severe constipation]. PMID- 1865938 TI - [Differences an health care delivery among 11 KNO partnerships in 2 catchment areas]. PMID- 1865939 TI - [A psychiatric disorder in an intensive care unit]. PMID- 1865940 TI - [Fluid accumulation in the pericardium in children]. PMID- 1865941 TI - [DNA studies in proximal spinal muscular atrophy]. PMID- 1865942 TI - [Lidocaine-prilocaine ointment; a welcome addition in local anesthesia]. PMID- 1865943 TI - [Effect of zinc oxide tape on plantar ulcers in leprosy patients in Indonesia]. AB - In this investigation the effectiveness was studied of adhesive zinc oxide tape, as additional therapy to the usual application of povidone iodine (10%), for leprosy patients with plantar ulcers in Sulawesi Tengah, Indonesia. The effectiveness (degree of wound healing measured as surface reduction) of this experimental therapy was compared with that of the usual therapy alone. At the same time the influence of the physical activity level on the effectiveness of both therapies was studied. During six weeks 38 leprosy patients with simple ulcers were treated with either one of the therapies. The average wound healing of the experimental group and the control group was 388 mm2 (SD 498) and 260 mm2 (SD 260) respectively. Using the t-test, there was no statistically significant difference in wound healing between the two therapies (p = 1.7). The average wound healing of the experimental group with a high and a low activity level was 342 mm2 (SD 226) and 405 mm2 (SD 571) respectively. The average wound healing of the control group with a high and low activity level was 246 mm2 (SD 289) and 275 mm2 (SD 232) respectively. Using analyses of variance, there was no statistically significant influence on the effectiveness of the therapies (p greater than 0.1). Methodological problems possibly influenced on the results. Different problems which may be encountered during research in third world countries are mentioned. PMID- 1865944 TI - [(Procto)colectomy with permanent ileostomy versus restorative proctocolectomy in ulcerative colitis; the past as background for the present]. AB - In the University Hospital of Utrecht, in order to assess the value of 'restorative' proctocolectomy, the early and late complications after 'classical' (procto)colectomy with establishment of a permanent ileal stoma were evaluated retrospectively over the period 1969-1988. The inclusion criteria were: having undergone a (procto)colectomy with establishment of an ileal stoma because of pathologico-anatomically confirmed ulcerative colitis, with follow-up in the clinic mentioned. Data on the preoperative period, on the operation and on the early and late complications were collected of 101 patients. Immediately postoperative complications were encountered in 50% of the patients. Mortality was 2% in the group as a whole and 5% after emergency surgery. Late complications occurred in 62% of the patients, and in 45% of the patients they necessitated one or several reoperations. Sources of late complications included: the rectal stump left in situ, the perineal wound area, the stoma and the formation of abdominal adhesions. Classical (procto)colectomy with establishment of a permanent ileal stoma entails a large proportion of early and late postoperative complications. It is asserted that the complications at present observed after restorative proctocolectomy must not prompt a return to classical proctocolectomy as the standard surgical treatment of ulcerative colitis. PMID- 1865945 TI - [Chronic atrophic acrodermatitis; a deceptive form of Lyme borreliosis]. AB - Acrodermatitis chronica atrophicans (ACA) was diagnosed in 15 patients from the southern and eastern part of Friesland (the Netherlands). Twelve patients had one leg affected; three had more than one extremity involved. Frequent complaints were fatigue, paraesthesia, swelling and blue discoloration. The symptoms persisted for many years in most cases. The inflammatory stage was observed most frequently (13/15): violet-blue erythema, oedema, firm swelling and nodules. Atrophy (4/15) was observed once in the form of a scleroderma-like lesion. Neuropathy was found in five patients. Histological investigation showed infiltration with lymphocytes and plasma cells (13/15) and atrophy (2/15). Spirochaetes were demonstrated in biopsies of 13 patients. Specific antibodies against Borrelia burgdorferi were found in all patients. ACA appears to be not infrequent and must be distinguished from other inflammatory and vascular diseases, such as chronic venous insufficiency. PMID- 1865946 TI - [Breast-preserving therapy: shorter treatment period with peroperative placement of iridium guide-needles]. PMID- 1865948 TI - [The treatment of surgical patients in an intensive care unit in a peripheral hospital]. PMID- 1865947 TI - [Unnecessary delay in vulvar carcinoma]. PMID- 1865949 TI - [Brain infarct; current developments]. PMID- 1865950 TI - [Review of the reference model for family practitioner information systems of the Work Group Coordination Information Automation]. PMID- 1865951 TI - [Reported patients with infectious diseases in 1990]. AB - The number of cases of infectious diseases notified in 1990 in accordance with the Infectious Diseases Control and Disease Cause Act are given. Of each A, B and C disease the figures are given separately. The most significant changes as compared with the previous years are discussed. PMID- 1865952 TI - [Measurement of the quality of care for surgical patients in an intensive care unit in a peripheral hospital]. AB - OBJECTIVE: To determine the quality of care in an intensive care unit. DESIGN: Prospective investigation for one year. Comparison with results from the literature. SETTING: Surgical intensive care unit of a community hospital. PATIENTS: Measurement of the APACHE-II-score was performed on days 1, 3 and 7 in all surgical intensive care unit patients admitted during a one-year period. The predicted mortality from the literature was compared with the actual mortality in our hospital. RESULTS: A total of 301 patients were admitted to the intensive care unit. Overall mortality was 9%. All the patients with an APACHE II score above 25 on admission died. The actual mortality was comparable with the predicted mortality from the literature. CONCLUSION: The APACHE II score can be used to determine the quality of care in an intensive care unit. Early prediction of a bad prognosis makes transportation to a more specialized hospital possible, before irreversible organ damage develops. PMID- 1865954 TI - [Validity of the cognitive screening test and the mini-mental status examination in a group of elderly health insurance patients]. PMID- 1865953 TI - [Anaphylaxis induced by exertion]. AB - A 44-year-old man with a two-year history of episodes of exercise-related urticaria and facial angioedema was admitted to our department because of vascular collapse during an athletic activity. The diagnosis of exercise-induced anaphylaxis was established after excluding other causes of shock. This clinical syndrome was described recently; it consists of urticaria, local angioedema and/or cardiorespiratory failure following exercise. Factors possibly associated with or predisposing to attacks include personal and family histories of atopy, food ingestion and weather conditions. Not every effort evokes these reactions, indicating the presence of other, still unknown variables and therefore complicating the diagnosis because provocation tests often have false-negative results. With reference to this case, the clinical syndrome, its pathophysiology and its treatment are discussed. PMID- 1865955 TI - [Intolerance of ambiguity in affective and schizophrenic disorders]. AB - In a study of determine the relationship between intolerance of ambiguity and different psychiatric disorder classified according to DSM-III and DSM-III-R criteria, 68 inpatients, 46 outpatients at the Psychiatric Clinic of the University of Heidelberg und 25 normal subjects completed the Kischkel Intolerance of Ambiguity Scale as well as other psychometric instruments. The group of unipolar depressive inpatients showed significantly higher scores than the control group and the schizophrenic group. Among the outpatients without clinical symptoms the group of unipolar depressives also showed significantly higher scores than the control group and the schizoaffective group. No differences were found between unipolar and bipolar individuals. Intolerance of ambiguity did not show no significant correlations with age, depressivity or anxiety scores. The meaning of this 'intolerance of ambiguity' among unipolar depressive patients is discussed. PMID- 1865956 TI - [Paraphrenia in the elderly. Psychopathologic and computer tomography indications of two subtypes]. AB - Psychopathological and cranial computed tomography findings in 48 patients with late paraphrenia were compared with the findings in 40 normal controls. 19 patients with late paraphrenia and first rank symptoms showed significantly less cortical atrophy than 29 patients without first rank symptoms (p less than 0.01). There were no significant differences of ventricular enlargement, cerebellar atrophy, the presence of leukoaraiosis or basal ganglia mineralisation between the late paraphrenic and control groups. In contrast to the controls, cortical atrophy, ventricular enlargement and the presence of leukoaraiosis were not age related. These results may indicate different origins of late paraphrenia with or without first rank symptoms. PMID- 1865957 TI - [Manifestations of Alzheimer's disease in daily living]. AB - From the perspective offered by diagnostic criteria, cognitive rating scales and psychometric tests, Alzheimer's disease appears to be primarily a continuous decline of memory and intelligence. Changes in other areas of behaviour often go unrecognized at examination or are considered insignificant. A completely different view is offered by the reports of care-givers. Here, impairment of everyday activities, abnormal emotional and social behaviours are the most important features. To examine the everyday manifestation of Alzheimer's disease at greater detail, a questionnaire for care-givers was developed. Observations of patients' behaviours as recorded on this instrument demonstrate the presence of significant changes of affect and drive even in mild stages of the disorder. They show only weak associations with cognitive symptoms and cannot be explained as psychological reactions. The non-cognitive aspects of Alzheimer's disease deserve particular diagnostic and therapeutic interest. PMID- 1865958 TI - [The effectiveness of therapeutic horseback-riding in the treatment of chronic schizophrenic patients. Experimental results and clinical experiences]. AB - After describing horse-riding as a facility in managing mentally ill patients, a program for chronic schizophrenic in-patients is presented. Clinical experience with this program and also results of a controlled study are reported. The therapeutic value and slope for horse-riding are discussed in relation to different diagnoses. PMID- 1865959 TI - [Onset of the antidepressive effect of rolipram, an antidepressant with a new mechanism of action, in comparison with imipramine]. PMID- 1865960 TI - [Sleep polygraphic studies as an objective method for assessing the therapeutic result in a case of periodic hypersomnia (Kleine-Levin syndrome)]. PMID- 1865961 TI - [Cardiovascular irregularities in schizophrenia--more than an epiphenomenon?]. PMID- 1865962 TI - [Compulsory patient admission--a psychiatric risk group]. PMID- 1865963 TI - [Time perspective in the treatment of elderly depressed patients]. AB - Coping with depressive illness in old age is impeded by particular strains: an increasing incidence of loss events, physical constraints, lack of social support and narrowing prospects for the future may lead to relapse as well as retarded recovery or chronification. Treatment directed toward long-term rehabilitation therefore requires, in addition to medical measures, psychotherapeutic and social interventions which help the patient cope with past loss, solve current problems and open up new perspectives for the future. This integration would overcome a dichotomy, still prevalent in psychotherapy for the elderly, between retrospection and life review on the one hand, activation and extension of competence on the other--or "involution" versus "evolution". A therapeutic approach which thus integrates personal aspects of the past, present and future may also combine various methods such as reminiscence therapy, interpersonal therapy, behavioral and social interventions. PMID- 1865964 TI - [Drug treatment of compulsive disorder]. PMID- 1865965 TI - [Magnesium in neurology]. PMID- 1865966 TI - Improved physical performance after treatment of renal anemia with recombinant human erythropoietin. AB - The physical performance of 12 anemic patients on renal dialysis was investigated following treatment of renal anemia with recombinant human erythropoietin (rhEPO; 40-120 U/kg, 3 times a week). Exercise intensity at a heart rate of 130 beats/min (PWC130) on a bicycle ergometer was assessed before rhEPO treatment, after reaching the target hematocrit (73 +/- 18 days), and in the maintenance phase (211 +/- 53 days). Hemoglobin concentrations measured at these time points were 7.3 +/- 1.2, 11.9 +/- 1.5, and 12.1 +/- 1.4 g/dl, respectively. PWC130 rose from 77 +/- 27 to 104 +/- 37 and 104 +/- 51 W, respectively. Aerobic threshold (i.e. blood lactic acid concentration of 2 mmol/l) shifted to higher workloads indicating improved muscle oxygen supply. PMID- 1865967 TI - Hemodynamic changes in hemodialyzed patients during treatment with recombinant human erythropoietin. AB - Evolution of cardiac index in 12 patients with severe renal anemia on regular hemodialysis (hematocrit 19.9 +/- 2.8%) was studied during the first 4 months of treatment with recombinant human erythropoietin (rhEPO). At the end of the study period, hematocrit rose to 31.1 +/- 3.5% (p less than 0.001) and cardiac index significantly decreased (5.34 +/- 1.25 vs. 3.81 +/- 0.84 liters/min/m2, p less than 0.001). Cardiac index fell mainly because of reduction of stroke volume (108 +/- 27 vs. 81 +/- 25 ml, p less than 0.001), while heart rate did not change during the study period. Before starting rhEPO cardiac index was elevated in 11 out of the 12 patients, whereas after 4 months of treatment this was only maintained in 4 of them. We conclude that substitution with rhEPO in hemodialysis patients significantly decreases cardiac index, confirming anemia as the main factor for hyperdynamic circulatory state in these patients. Whether this reduction in cardiac index will ameliorate cardiac morbidity or not and hematocrit levels for achieving the major benefits require further studies. PMID- 1865968 TI - Immunoreactive serum calcitonin and skeletal histology in chronic renal failure. AB - Serum calcitonin and serum parathyroid hormone (PTH) were measured in 50 patients undergoing regular haemodialysis for end-stage chronic renal failure, and an analysis of osteoclast and osteoblast activities was made in bone biopsies obtained by iliac crest trephine. Osteoclast and osteoblast activities were studied in a multivariate analysis in relation to factors which might reasonably be thought to influence activity, namely serum calcitonin, serum PTH, serum calcium, serum inorganic phosphate, and bone aluminium. Only serum PTH correlated strongly with osteoclast activity (p = 0.0047). Serum PTH correlated also with osteoblast activity (p = 0.0024). Serum inorganic phosphate correlated negatively with osteoblast activity (p = 0.0082). Serum calcitonin did not correlate with osteoclast or osteoblast activities but did correlate strongly with bone aluminium in a multivariate analysis (p = 0.0078). Bone aluminium did not correlate independently with osteoclast or osteoblast activities. This study affirms the implied powerful role of PTH in influencing osteoclast and osteoblast activities in end-stage chronic renal failure. PMID- 1865969 TI - Lack of relationship between parathyroid hormone and 1,25-dihydroxyvitamin D in chronic renal failure. AB - In the present study, concentrations of parathyroid hormone (PTH), determined by an intact PTH assay and a midregion/C-terminal PTH assay, 1,25-dihydroxyvitamin D [1,25(OH)2D3], ionized calcium and phosphate were measured in 15 patients with a stable creatinine clearance (Ccr) of 21.2 +/- 14.4 ml/min (mean +/- SD; group 1) and in 10 patients with a Ccr regularly undergoing hemodialysis (group 2, Ccr not measured). In group 1, the mean concentration of 1,25(OH)2D3 was significantly increased compared with the level in group 2, whereas no differences were found concerning the concentrations of intact PTH, midregion/C-terminal PTH, ionized calcium and phosphate. In group 1, the PTH concentration correlated inversely with ionized calcium concentration and Ccr, which in turn, was directly correlated. The concentration of 1,25(OH)2D3 correlated inversely with phosphate concentration, but did not correlate with either PTH or ionized calcium concentrations. In group 2 no correlation was found between any of the biochemical variables. The data demonstrate that in patients with stable renal failure, the concentration of ionized calcium still regulates PTH secretion but other variables such as parathyroid cell mass and setpoint may interfere with the interrelation. The elevated concentration of phosphate in renal failure may override PTH as a regulator of the renal 1,25(OH)2D3 formation. The lack of correlation in the hemodialyzed patients may be attributed to extrarenal production of 1,25(OH)2D3, reduced binding of 1,25(OH)2D3 to parathyroid tissue or the major changes in calcium homeostasis caused by the hemodialysis. PMID- 1865970 TI - Effects of rhubarb tannins on uremic toxins. AB - The effects of each of several tannins purified from Rhei Rhizoma on serum constituents were investigated in rats with adenine-induced renal failure. Blood levels of urea nitrogen, methylguanidine (MG), and guanidinosuccinic acid (GSA) were significantly decreased in rats given (-)-epicatechin 3-O-gallate at a dose of 2.5, 5 or 10 mg/kg body weight/day for 24 days. The creatinine (Cr) level was also significantly decreased in rats given 5 and 10 mg of this compound. A significant decrease in urea nitrogen, MG, and GSA was found in rats given 6.25 mg of procyanidin B-2 3,3'-di-O-gallate. However, unlike the former two components the administration of 12.5 mg of procyanidin C-1 3,3',3''-tri-O gallate produced a considerable or significant increase in bLood levels of urea nitrogen, Cr, MG, and GSA. RG-tannin had a weaker overall effect on serum constituents except for GSA in comparison with the corresponding effect of (-) epicatechin 3-O-gallate and 6.25 mg of procyanidin B-2 3,3'-di-O-gallate. Rhatannin tended to increase the serum nitrogen constituents. PMID- 1865971 TI - Microalbuminuria is acutely increased during anesthesia and surgery. AB - Microalbuminuria is known to increase in various diseases with potential repercussion on the kidneys and indicates an increase in glomerular intracapillary pressure or changes in permeability characteristics. In this study, we measured whether albumin excretion is affected in patients undergoing anesthesia and surgery, which are both known to induce dramatic changes in renal function and in the release of vasoactive substances such as catecholamines, vasopressin, angiotensin, and prostaglandins. Seven patients with normal renal function and physiological microalbuminuria prior to surgery were studied. Urine samples were collected before anesthesia, just before the beginning of surgery, and thereafter 30 min following incision, and 30 min after the end of surgery. Anesthesia induced a significant increase in microalbuminuria, which further increased during surgery. After the end of surgical procedure, microalbuminuria decreased but remained significantly higher than control. This phenomenon may be due to an increase in intracapillary glomerular pressure and/or an alteration in glomerular permeability induced by a direct effect of drugs, or to the action of vasoactive substances on the glomerular structure. PMID- 1865972 TI - Elevated dietary protein intake impairs the renal hemodynamic response to hyperaminoacidemia in patients with primary glomerular diseases. AB - We have evaluated the renal hemodynamic response to a mixed amino acid infusion in 7 control subjects and in 8 patients with primary glomerulonephritis (GN). In order to evaluate the role of dietary protein intake in this response, GN patients were maintained for 3 weeks on two separate dietary regimens providing 130 +/- 5 g of protein/day (study 1) and 60 +/- 3 g of protein/day (study 2), respectively. Normal subjects were studied while consuming a free diet. In GN patients, following the reduction in dietary protein intake basal RPF and GFR decreased from 589 +/- 109 to 422 +/- 81 ml/1.73 m2/min (p less than 0.01, vs. study 1) and from 75 +/- 7 to 70 +/- 8 ml/1.73 m2/min (p = NS). Filtration fraction rose from 0.14 +/- 0.02 to 0.19 +/- 0.03 (p less than 0.05). In study 1, during amino acid infusion GFR and RPF did not change significantly from baseline (75 +/- 7 vs. 66 +/- 8 ml/1.73 m2/min at 180 min and 589 +/- 109 vs. 567 +/- 102 ml/1.73 m2/min, respectively). These results are at variance with data obtained in normal controls in whom both GFR and RPF rose significantly following hyperaminoacidemia. In contrast, when dietary protein intake was reduced, a normal renal hemodynamic response to amino acid infusion was restored (GFR went from 70 +/- 8 to 90 +/- 18 ml/1.73 m2/min and RPF from 422 +/- 81 to 517 +/- 90 ml/1.73 m2/min, both p less than 0.05 vs. basal), both absolute and percentage increases were similar to what was observed in controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865973 TI - Aluminium determination in the skin of patients with and without end-stage renal failure. AB - Aluminium (Al) concentration in the skin was determined by inductively coupled plasma optical emission spectrometry to look for a correlation between Al exposure and skin content in patients with end-stage renal failure. Skin Al concentrations were higher in dialyzed patients than in the nondialyzed group (1.02 +/- 0.30 vs. 0.26 +/- 0.10 micrograms/g; p less than 0.001). Moreover, in the dialyzed group, the patients treated for more than 100 months had a higher concentration of Al in the skin than the others (1.20 +/- 0.26 vs. 0.80 +/- 0.18 micrograms/g; p less than 0.05). Al skin content correlated better with the deferoxamine infusion test (DIT) than with Al blood plasma concentration. In conclusion, our data confirm that the DIT is a valuable tool for the evaluation of body Al content. PMID- 1865974 TI - Bicarbonate and calcium kinetics in postdilutional hemodiafiltration. AB - Hemodiafiltration (HDF) is a very effective blood treatment resulting from the coupling of dialysis and hemofiltration and leading to reduction of dialysis time. The aim of this study was to evaluate the balance of bicarbonate and calcium through the filter during postdilutional HDF (with an ultrafiltration flow rate of 70 ml/min) and to verify the effect of ultrafiltration on the kinetics of these two solutes. The study was performed by simultaneously collecting three blood samples (at filter inlet and outlet and after reinfusion) at different ultrafiltration flow rates (12.5-90 ml/min), to measure blood pH, pCO2, plasma total CO2(TCO2), total calcium, ionized calcium and plasma protein concentration. Plasma bicarbonate concentration was calculated by measuring plasma TCO2. The results showed an inverse linear relationship between bicarbonate (r: -0.7938; p less than 0.001) and calcium (r: -0.8731; p less than 0.001) balance and ultrafiltration flow rate. In particular, in postdilutional HDF both bicarbonate and calcium balances through the filter were negative at ultrafiltration flow rates greater than 40 and 55 ml/min, respectively. The negative bicarbonate balance, however, was corrected by reinfusing a substituting solution containing bicarbonate (40 mmol/l). By contrast, the negative calcium balance cannot be corrected by reinfusion and requires a greater calcium concentration in the dialysate and oral calcium supplements. PMID- 1865975 TI - Evaluation of a region-wide hepatitis B vaccination program in dialysis patients: experience in an Italian region. The Latium Hepatitis Prevention Group. AB - In 1985-1986, 634 adult dialysis patients were tested prior to hepatitis B vaccination, representing 40% of the total patients in Latium, an Italian region. HBsAg and anti-HBs prevalences were 7.1 and 36.0%, respectively. Merck, Sharp & Dohme (MSD) and Pasteur plasma-derived vaccines were randomly allocated to the 44 dialysis units. An anti-HBs response greater than or equal to 10 IU/l was elicited in 58.5% of 236 subjects tested at 6 months, 63.4% MSD and 52.4% Pasteur (p n.s.). The relatively low response to the vaccine in this high-risk group stresses the need to improve the efficacy of the vaccination and to maintain policies of environmental control. PMID- 1865976 TI - Glycosaminoglycans, albuminuria and hydrocarbon exposure. AB - The value of the glycosaminoglycans (GAG) determination in urine was examined in a population of hydrocarbon-exposed workers and compared to the usefulness of the fractional albumin clearance (FAC). Blood pressure and hydrocarbon exposure interact to increase the FAC but the GAG concentration seems less useful because too many other variables influence it as well. PMID- 1865977 TI - Experience with vascular access for acute renal failure: using Buselmeier shunt and femoral vessel catheter. AB - Three types of vascular access were evaluated over a period of 2 years, January 1987-December 1989, in 76 critically ill acute renal failure (ARF) patients. The Buselmeier shunt comprised 75% of the acute vascular access which were utilized, the cannulation of the femoral vessel 23% and the Scribner shunt 2%. The Buselmeier shunt was successfully used alone (mainly in the forearm) in 58 patients for continuous arteriovenous hemofiltration, continuous arteriovenous hemodialysis and intermittent hemofiltration. Thrombosis was noted in 7% of the shunts, where the majority needed a new shunt either on the same or the contralateral arm. Blood leakage was noted in 2%, hematoma in 1%, and accidental bleeding in 1% of the shunts. This study showed that the Buselmeier shunt is more used in our center, most likely because it is easy to bypass the hemodialysis filter by the staff nurse in case of clotting. No major complications were noted even if kept in place for a longer period of time. It offers adequate blood flow for continuous renal replacement therapy and intermittent hemofiltration in ARF. PMID- 1865978 TI - Hemodialysis-associated cardiac arrhythmias: a lower risk with bicarbonate? AB - The role of hemodialysis (HD) as an arrhythmogenic event has recently been emphasized. We studied 18 patients by Holter monitoring, comparing the arrhythmogenic effect of acetate dialysis (AHD) and bicarbonate dialysis (BHD). The frequency of ventricular arrhythmias was 93 +/- 66/h in AHD and 32 +/- 26/h in BHD (p less than 0.005). According to the classification of Lown and Graboys, classes III and IV were more often to be found in AHD than in BHD and no patient on BHD was in class IVB and class V. Five patients affected with ischemic heart disease had more frequent and dangerous ventricular arrhythmias than the others; a significant difference between buffers was recorded in all cases but 1. Intradialytic changes in body weight, hematocrit, osmolarity, ionized calcium and potassium during AHD and BHD were similar. The two methods only differed in the quickness and degree of correction of acidosis, and this was related to a significant difference in intraerythrocytic potassium at the end of the session. The quicker and more regular correction of acidosis with BHD and the consequent difference in ionic flows between the intra- and extracellular spaces, as demonstrated by changes in intraerythrocytic potassium at the end of the session, could account for the seemingly less arrhythmogenic effect of BHD. PMID- 1865979 TI - Examination of aggravating factors of urinary excretion of N-acetyl-beta-D glucosaminidase after extracorporeal shock wave lithotripsy. AB - We measured urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion before and after extracorporeal shock wave lithotripsy (ESWL) with a view to study the underlying factors which aggravate renal impairment immediately after ESWL. The factors associated with the significant elevation of urinary NAG after ESWL included female sex, a previous history of ESWL, and urinary tract infection (UTI). By studying the backgrounds of these factors, we found that both the female group and the group with a previous history of ESWL contained significantly more patients with UTI. These findings indicate that UTI may be one of the risk factors which aggravate renal damage immediately after ESWL, and that careful management is necessary in the ESWL treatment of urinary tract stones with UTI. PMID- 1865980 TI - Unique glomerular lesion with spontaneous lipid deposition in glomerular capillary lumina in the NON strain of mice. AB - We found a strain of nonobese, nondiabetic (NON) mice which has spontaneous lipid deposition in glomerular capillary lumina. This strain was developed together with a diabetic strain of nonobese diabetic (NOD) mice for the generation of mouse models of diabetes mellitus. In the NON strain, contrary to the name, impaired glucose tolerance (IGT) was observed in about half of the mice. Meanwhile, peculiar glomerular abnormalities which remotely resemble those of diabetic nephropathy were observed in the NON strain. The lesions were characterized by massive lipid accumulation with proteinaceous material within the glomerular capillary lumina. In addition, positive staining for immunoglobulins, especially IgM, was observed by immunofluorescence microscopy. The overall frequency of this lesion was 91%. Mesangiolysis, capillary ballooning with many small lipid vesicles were the striking features by electron microscopy. Histochemical analysis revealed the presence of various lipids in these lesions. However, as far as we examined, these lesions did not correlate with hyperlipidemia or IGT. Lymphoid follicle-like structures were seen around the renal arterioles. The cellular components of these lymphoid follicles reacted with monoclonal antibodies to L3T4. High levels of serum immunoglobulins were observed in this strain. We suppose that the immunological disorders may have some bearing in the evolution of this lesion in NON mice. We believe that this model may be of use in studying the role of lipid derangements in renal diseases. PMID- 1865981 TI - Insulin-like growth factor 1 and renal growth following ureteral obstruction in the rat. AB - The role of insulin-like growth factor 1 (IGF-1) in renal growth of obstructed and contralateral kidneys was investigated for 10 days following unilateral ureteric obstruction in male Wistar rats. The weight of the obstructed kidney increased rapidly, rising from 671 +/- 10 to 1,378 +/- 42 mg on day 10, an increase of 105%. IGF-1 content of the obstructed kidney was significantly less than in control kidneys from day 2 onwards, reaching a nadir of 70 ng/mg, a fall of 64%. The protein concentration, expressed as milligrams per gram kidney weight, also fell rapidly from 141 +/- 11 to 88 +/- 3 mg/g on day 6. The weight of the contralateral kidney increased by 32%, from 671 +/- 10 to 887 +/- 48 mg on day 10. The IGF-1 content of this kidney was increased by 48% from baseline on day 1 (268 +/- 23 vs. 191 +/- 13 ng/g) and remained increased compared to sham operated animals on days 6 and 8. The protein content, expressed as milligrams per gram kidney weight, remained constant throughout the study. We conclude that in the acutely obstructed left kidney increasing kidney weight is associated with falling concentration of IGF-1 and protein and may be due to oedematous and reactive change. Growth of the contralateral kidney is preceded by a rise in the concentration of IGF-1 and may represent true renal compensatory growth. PMID- 1865982 TI - Lead stores in patients with renal insufficiency. PMID- 1865983 TI - Effect of carbamazepine on cyclosporin blood level. PMID- 1865984 TI - Anti-glomerular basement membrane nephritis due to hydralazine. PMID- 1865985 TI - Absence of mesangial IgA in AIDS: a postmortem study. PMID- 1865986 TI - Mechanism of kidney stone formation in chronic hemodialysis patients. PMID- 1865987 TI - Detection of circulating immune complexes in patients on hemodialysis by a new immunoassay. PMID- 1865988 TI - Decreased need for blood transfusion during one year after discontinued erythropoietin treatment in haemodialyzed patients. PMID- 1865989 TI - Extremely prolonged half-life of prostacyclin in plasma causative for bleeding in an uremic patient? PMID- 1865990 TI - Low-protein diet and renal osteodystrophy. PMID- 1865991 TI - Follow-up of lipid and apoprotein levels in renal transplant recipients. PMID- 1865992 TI - Galanthamine: pharmacokinetics, tissue distribution and cholinesterase inhibition in brain of mice. AB - Galanthamine was determined in plasma and tissue extracts of mice, after the application of 4, 6 and 8 mg/kg (i.v.), by reverse phase HPLC, with fluorescence detection. A biexponential decline of concentrations in plasma, with a terminal half-life of 43.3 min, was observed after the dose of 4 mg/kg. The volume of distribution (Vss) of 2.17 l/kg was similar to that found in other species, including man. Metabolism to the inactive diastereomer, epigalanthamine, was very limited. There was a rapid accumulation of galanthamine in tissues, which was most pronounced in the kidney (10-fold compared to plasma) and liver (5-fold). In brain, accumulation was similar to other parenchymatous organs (diaphragm, lung) and amounted to 2.10-fold. Red blood cells showed a concentration 1.34-fold greater than plasma. The accumulation of galanthamine in tissue, with the exception of liver and kidney, can be explained by passive distribution according to differences in pH, between intra- and extracellular compartments. Extraction of galanthamine from blood to brain tissue was complete, indicated by a clearance in the range of cerebral blood flow (1.05 ml min-1 g-1). The concentration-time course of galanthamine in brain tissue was parallel to that in plasma during the terminal elimination phase. Measurement of inhibition of acetylcholinesterase (AChE) in the same samples from brain revealed a maximum apparent inhibition of 43% in the homogenate of brain (1:4 w/v in phosphate buffer, 4 mg/kg, 5 min after injection).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1865993 TI - The effect of theophylline and immobilization stress on haloperidol-induced catalepsy and on metabolism in the striatum and hippocampus, studied with lactography. AB - Whether inducing catalepsy in the rat by an intraperitoneal injection of haloperidol (0.5 mg/kg) had an effect on metabolism in the striatum and in the hippocampus, as determined by lactography, and whether reducing the cataleptic state with stress or theophylline (8 mg/kg i.v.) had any impact on metabolism in these two regions of the brain was investigated. Furthermore, whether theophylline reduced catalepsy in rats through the adrenals was investigated. Haloperidol caused a significant increase in the metabolism of lactate, both in the striatum and in the hippocampus. Reducing haloperidol-induced catalepsy with short-term immobilisation stress did not affect the metabolism of lactate, neither in the striatum nor in the hippocampus. Reducing haloperidol-induced catalepsy with theophylline caused a significant rise in the metabolism of lactate in the striatum, while no effect was seen in the hippocampus. Adrenalectomy did not compromise the anti-cataleptic property of theophylline. It is concluded theophylline is a potent antagonist of haloperidol-induced catalepsy, and that this effect is not mediated by the adrenals. Furthermore, it is reported that haloperidol influenced metabolism in regions of the brain not considered to be its primary target. Lactography is considered to be a very useful tool in the study of metabolism during activity. PMID- 1865994 TI - Involvement of the dorsal hippocampus in mediation of the antianxiety action of tandospirone, a 5-hydroxytryptamine1A agonistic anxiolytic. AB - The effect of tandospirone, a 5-hydroxytryptamine (5-HT)1A agonist/anxiolytic, injected directly into dorsal hippocampus, on Vogel-type conflict behavior in rats was investigated and the findings were compared with the effects of diazepam and zopiclone. Tandospirone (30 micrograms/2 microliters and 60 micrograms/2 microliters) and diazepam (40 micrograms/2 microliters) but not zopiclone (20 micrograms/2 microliters), produced a potent anticonflict action in rats. The anticonflict action of tandospirone (30 micrograms/2 microliters), injected into the dorsal hippocampus, was significantly blocked by (-)-propranolol (5 mg/kg i.p.). The present findings provide evidence that suggests that tandospirone has an antianxiety action, presumably by stimulating 5-HT1A receptors in the dorsal hippocampus. PMID- 1865995 TI - Neonatal exposure to therapeutic caffeine alters the ontogeny of adenosine A1 receptors in brain of rats. AB - Caffeine is a methylxanthine, commonly used in the premature neonate to treat apnea of prematurity. It is efficacious and appears to have few short-term side effects. An animal model, designed to mimic the developmental period in brain and level and duration of exposure in humans, was used to investigate possible long term effects of early developmental exposure to caffeine on the ontogeny of the adenosine receptor to which caffeine binds. Specific binding at the adenosine A1 receptor, in five distinct regions of the brain was determined in rats, 14-90 days old, as a function of early postnatal exposure to caffeine, over days 2-6. In cortex, cerebellum and hippocampus but not in the brain stem or hypothalamus, there was an increase in specific binding, following neonatal exposure to caffeine, compared to specific binding in control animals. Kinetic analysis of binding to the A1 site in cortical tissue suggests that this increase was due to an increased maximum binding density (Bmax); binding affinity (Kd) did not change. Thus, limited exposure to caffeine, in the early neonatal period, may result in up-regulation of the adenosine A1 receptor that persists to young adulthood in the rat. PMID- 1865996 TI - Nifedipine has paradoxical effects on the development of kindling but not on kindled seizures in amygdala-kindled rats. AB - The effects of nifedipine, an antagonist of voltage-operated calcium channels, on the development of amygdala kindling and on the production of fully kindled seizures, stimulated from the amygdala, were investigated. Rats were treated daily with two doses (5 and 50 mg/kg, i.p.) of nifedipine during the development of kindling. Both doses of nifedipine retarded the development of kindled seizures and 50 mg/kg of nifedipine prolonged the latency to the occurrence of bilateral forelimb clonus. In contrast to these antiepileptogenic effects, however, both doses also increased the duration of afterdischarge. This resulted in a striking increase in the cumulative duration of afterdischarge, required to reach stage 4 and 5 seizures. Contrary to the results of a previous study, 50 mg/kg of nifedipine did not produce any significant effect on fully kindled seizures, regardless of the interval (5 min-24 hr) between injection and stimulation of kindling. These results suggested that although nifedipine inhibited the propagation processes of seizures during development of kindling, it appeared to increase the duration of epileptic activity at the kindling focus. PMID- 1865997 TI - 2-propyl-1-aminopentane, its deamination by monoamine oxidase and semicarbazide sensitive amine oxidase, conversion to valproic acid and behavioral effects. AB - 2-Propyl-1-aminopentane (2-PAPN), a branched aliphatic amine, was found to be readily deaminated by monoamine oxidase B in the liver of the rat and semicarbazide-sensitive amine oxidase in the aorta of the rat. The deaminated product, 2-propyl-1-pentaldehyde, could be subsequently converted to valproic acid in the presence of aldehyde dehydrogenase and beta-NAD cofactor in vitro as well as in vivo. Valproic acid was identified after derivatization with 4 bromomethyl-6,7-dimethoxycoumarin, followed by HPLC-fluorometric assessment. Absorption and biotransformation of a single intraperitoneal dose of 2-PAPN resulted in the rapid appearance of the drug and its metabolite in the blood and in the brain. The formation of valproic acid from 2-PAPN in vivo, however, was insufficient to facilitate anticonvulsant action. In fact, 2-PAPN itself, at relatively small doses, exhibited distinct tremor effects. Such tremor effects could be prevented by valproic acid. However, 2-PAPN was also found to potentiate the convulsant effect induced by mercaptopropionic acid (MPA) and, in addition, the 2-PAPN-induced tremor could be potentiated by MPA in mice. PMID- 1865998 TI - Geriatric neurology. PMID- 1865999 TI - Added qualification in clinical neurophysiology. PMID- 1866001 TI - Botulinum toxin treatment of tremors. AB - We report the results of an open trial of botulinum toxin (Botox) in the treatment of 51 patients with disabling tremors, classified as dystonic (14), essential (12), combination of dystonic and essential (22), parkinsonian (1), peripherally induced (1), and midbrain (1). The average age of the patients was 55.8 years, and duration of symptoms was 13.9 years. During a total of 160 treatment visits, an average of 242 +/- 75 units of Botox was injected per visit in cervical muscles of 42 patients with head tremor and 95 +/- 38 in forearm muscles of 10 patients with hand tremor; one patient was injected in both. The average peak effect for all patients was rated as 3.0 (0 to 4 scale). Thirty-five (67%) patients improved (peak effect greater than or equal to 1). The average latency from injection to response was 6.8 days, and the average duration of maximum improvement was 10.5 weeks. Local complications, lasting an average of 20.6 days, were noted in 17 (40%) patients injected for head tremor, consisting chiefly of dysphagia in 12 (29%), transient neck weakness in four (10%), and local pain in two (5%). Six (60%) patients with hand tremor had transient focal weakness. EMG recordings showed decreased amplitude of EMG bursts after Botox treatment. The results of this pilot study indicate that Botox injections can be used to control tremor in patients in whom other forms of therapy have failed. PMID- 1866000 TI - A comparative study of the cerebrovascular complications of cocaine: alkaloidal versus hydrochloride--a review. AB - Cocaine, especially in its alkaloidal or "crack" form, has been increasingly associated with cerebrovascular disease. Before the crack epidemic, cocaine hydrochloride (HCl) was also implicated as a cause of stroke. However, less is known about the differences in stroke subtypes, age at stroke onset, or presence of underlying structural cerebrovascular disease with different forms of cocaine use. We compared 26 patients (previously reported) from our four institutions plus 16 cases reported in the literature of stroke associated with alkaloidal cocaine to 63 (57 reported in the literature and six not previously reported from our four institutions) cases of stroke associated with cocaine HCl. Ischemic and hemorrhagic strokes are equally likely after alkaloidal cocaine use, whereas cocaine HCl is more likely (approximately 80% of the time) to cause hemorrhagic stroke, with approximately half the intracranial hemorrhages occurring from ruptured cerebral saccular aneurysms or vascular malformations. The presence of an underlying cerebral aneurysm was more common among patients with cocaine HCl associated strokes than alkaloidal cocaine-associated strokes. Cerebral infarction was significantly more common among the alkaloidal cocaine users than in all the cocaine HCl users, and this was also true when alkaloidal cocaine users were compared with parenteral cocaine HCl (intravenous and intramuscular) users. Only hemorrhagic stroke has been reported with intravenous cocaine HCl use. We conclude that the pathogenesis of cocaine-related stroke is heterogeneous, and depends, in part, on the form of cocaine used. PMID- 1866002 TI - The European Stroke Prevention Study: results according to sex. AB - The European Stroke Prevention Study was a multicenter trial comparing the effect of a combination of 75 mg dipyridamole and 330 mg acetylsalicylic acid tid with placebo in the prevention of stroke or death after one or more attacks of recent transient ischemic attacks or stroke of atherothrombotic origin. From the 2,500 patients in the intention-to-treat analysis, the proportion of women was 42%, and from the 1,861 patients in the explanatory analysis it was 44%. The endpoint incidence was significantly higher in men than in women. The endpoint reduction was statistically significant only in the intention-to-treat analysis with total endpoints. However, there was a marked percentage reduction of endpoints in both men and women in explanatory analysis. The risk reduction of strokes was 49% for men and 41% for women, and the reduction of total endpoints was 39% in men and 30% in women. Thus, antiplatelet therapy is effective in the prevention of stroke or death in both sexes. PMID- 1866003 TI - Cause of death in patients attending multiple sclerosis clinics. AB - Between 1972 and 1988, 145 deaths occurred among 3,126 patients attending the Multiple Sclerosis (MS) Clinics in Vancouver, British Columbia (N = 1,583), and London, Ontario (N = 1,543). We could determine the exact cause of death in 82.1% of cases (119 of 145). Of the 119 patients for whom the cause of death was known, 56 deaths (47.1%) were directly attributed to complications of MS. Of the remaining 63 deaths, 18 (28.6%) were suicides, 19 (30.2%) were due to malignancy, 13 (20.6%) to an acute myocardial infarction, seven (11.1%) to stroke, and the remainder (9.5%) to miscellaneous causes, of which two may have been suicides. The proportion of suicides among MS deaths was 7.5 times that for the age-matched general population, and the proportion of MS deaths from malignancy was 0.67 times that for the age-matched general population. The proportion of deaths due to malignancy and stroke was the same for the MS patients and the age-matched general population. PMID- 1866004 TI - Seizures caused by nontraumatic parenchymal brain hemorrhages. AB - Seizures occurred in 15% of patients with parenchymal brain hemorrhage (early in 12% and delayed in 3%). Seizures were most frequent with lobar hemorrhages and uncommon with deep subcortical hemorrhages. Lobar hemorrhages in the frontal, parietal, or temporal region were more commonly associated with seizures, whereas occipital hemorrhages were not. Seizures were most common if the hemorrhage was due to an aneurysm, angioma, or neoplasm and less common if hypertensive or spontaneous. If the patient had recurrent seizures or developed delayed seizures, CT showed that the hemorrhage evolved to a hypodense appearance; if the seizure did not recur, CT showed that the hemorrhage evolved to an isodense appearance. PMID- 1866005 TI - Spatial contrast sensitivity is reduced in bilateral Parkinson's disease. AB - We studied the contrast sensitivity functions of 41 patients with idiopathic Parkinson's disease (PD) with a wide range of parkinsonian symptomatology (Hoehn and Yahr stages 1 to 4) and 22 age-matched control subjects in a parametric design. Results demonstrated reduced contrast sensitivity in PD patients but only in those patients who had progressed beyond Hoehn and Yahr stage 1. Furthermore, there were deficits in contrast sensitivity related to the severity of PD. PMID- 1866006 TI - Optic chiasmal neuritis. AB - In four of six patients with clinical optic chiasmal neuritis, MRI demonstrated abnormalities of the chiasm. Optic chiasmal neuritis may be the initial manifestation of multiple sclerosis, a reflection of established CNS demyelination, or an isolated clinical finding. PMID- 1866007 TI - Leber's hereditary optic neuropathy: genetic, biochemical, and phosphorus magnetic resonance spectroscopy study in an Italian family. AB - Three siblings of a family affected with Leber's hereditary optic neuropathy (LHON) showed a mitochondrial DNA mutation at position 11778. The lactate response to a standardized effort was increased in only one case. Muscle biopsies and biochemistry of muscle and platelet mitochondrial enzymes were normal. All patients showed an altered energy metabolism during exercise and during recovery after exercise on phosphorus 31-magnetic resonance spectroscopy (31P-MRS) of muscle. Brain 31P-MRS showed a decreased energy reserve (decreased PCr/Pi ratio) in all patients. 31P-MRS noninvasively demonstrated an altered mitochondrial energy metabolism in muscle and, for the first time, in the brains of LHON patients. PMID- 1866008 TI - Preherpetic neuralgia. AB - We have encountered six zoster patients whose pain preceded rash by 7 to more than 100 days. Pain was severe, burning, and radicular, and located both in dermatomes different from, as well as in, the area of eventual rash. Two patients ultimately developed disseminated zoster with neurologic complications, one of zoster paresis, and the other, a fatal zoster encephalitis; both had been taking long-term, low-dose steroids. A third case of preherpetic neuralgia developed in a patient with prior metastatic carcinoma, and another case in a patient with an earlier episode of brachial neuritis. The final two cases of preherpetic neuralgia developed in individuals with no underlying disease. An extended period of pain before the onset of zoster rash has gone largely unrecognized. PMID- 1866009 TI - Quantitative MRI changes in gadolinium-DTPA enhancement after high-dose intravenous methylprednisolone in multiple sclerosis. AB - In 12 patients with definite multiple sclerosis who received a total of 21 courses of high-dose (1 gram daily for 10 consecutive days) intravenous methylprednisolone, we performed MRI of the brain with and without gadolinium DTPA before and after treatment. On the initial MRI, there was a total of 98 enhancing lesions, 93 of which were also represented on the unenhanced images. After treatment, 13 patients improved clinically, and 78 of the lesions lost enhancement but remained visible on the unenhanced images. There were six new enhancing lesions on the second MRI. Thus, the blood-brain-barrier integrity improved after high-dose IV methylprednisolone, which correlated well with the clinical improvement. The lesions remaining visible on the unenhanced images indicate an incomplete histologic recovery at the time of the second scan, and also demonstrate that unenhanced MRI alone is not sufficient to monitor disease activity in the short term in multiple sclerosis. PMID- 1866010 TI - Multifocal independent epileptiform discharges in children: ictal correlates and surgical therapy. AB - We obtained continuous EEG/video recordings on four children who had the interictal EEG pattern of multifocal independent epileptiform discharges (MIED). The prominent feature of their evaluation was the evidence that their clinical seizures appeared to be of focal origin; 42/44 seizures were manifested by "fencing postures." Three patients subsequently underwent epilepsy surgery: one focal resection of superior frontal-parietal cortex and two hemidecorticectomies. Seizure control improved in all three patients, and one patient is now seizure free. Our patients differ from those previously reported in that they had a predominance of tonic seizures and had no history of infantile spasms or Lennox Gastaut syndrome. Some patients, such as ours, with MIED may have clinical seizures of more focal origin than might be expected from their interictal EEG and, therefore, may benefit from resective epilepsy surgery. PMID- 1866011 TI - The spectrum of vertical gaze palsy following unilateral brainstem stroke. AB - A single unilateral lesion, near the midline, may interrupt the pathways involved in vertical gaze just before and after they decussate, inducing an anatomically unilateral, but functionally bilateral, lesion. We report 11 patients with supranuclear vertical gaze palsies (two with conjugate upgaze palsy, four with combined up- and downgaze palsies, two with monocular elevation palsy, and three with vertical "one-and-a-half" syndrome) due to unilateral midbrain strokes. PMID- 1866012 TI - Steroid-induced weakness in patients with primary brain tumors. AB - Clinically significant steroid myopathy (SM) occurred in 23 (10.6%) of 216 adult patients with primary brain tumors who received 2 or more continuous weeks of daily dexamethasone therapy. SM occurred over a wide range of peak and cumulative doses of dexamethasone as well as a wide range of periods of continuous treatment. This was not an entirely random event, however, as two-thirds of the patients developed their weakness during the 9th through the 12th week of continuous dexamethasone treatment. The risk of developing SM was significantly lower in patients taking phenytoin than in patients who were not taking anticonvulsants. The only other patient or treatment factor associated with SM was a possible direct correlation with the appearance of a cushingoid body habitus. In this retrospective review, the occurrence of SM had a significant negative impact on the quality of life of all affected individuals. As expected, patients who tolerated a reduction in their steroid dose improved, while other patients suffered the combined effects of tumor progression and worsening myopathy. Substituting a nonfluorinated glucocorticoid for dexamethasone is probably advisable if neuro-oncology patients affected by SM cannot be weaned from the steroids. PMID- 1866013 TI - Are demented patients with Parkinson's disease accurately reflected in prevalence surveys? A survival analysis. AB - We re-reviewed 257 patient records previously reviewed for an incidence study of dementia in Parkinson's disease (PD) to determine the frequency, date of death, and cause of death. We posited that if disease duration is shortened when dementia occurs, then dementia may be far more common than reflected in prevalence studies. There were 17 deaths among 65 demented patients and 28 deaths among 168 nondemented patients. When we matched a subset of the nondemented patients to the demented patients by age and disease duration distributions, the demented subjects had significantly more deaths (p less than 0.02), and survival among demented subjects was decreased (p less than 0.05). Dementia was a significant predictor of death in this sample. We conclude that dementia reduces survival in patients with PD. Incidence is a much better measure of dementia in PD than prevalence because shortened duration makes it less likely to detect dementia in prevalence surveys. PMID- 1866014 TI - Gaze-dependent hemianopia without hemispatial neglect. AB - A hemispheric field is the space defined by the midsagittal plane of the body. Hemianopia, in the absence of hemispheric spatial neglect, has been thought to be purely retinotopic. Confrontation testing of visual fields in eccentric positions of gaze in hemianopic patients permits the discrimination of hemispheric from retinotopic deficits. In the primary position of gaze, a patient with an ischemic lesion of the right occipital and temporal lobes, who was without unilateral spatial neglect, was unable to detect finger movement, name objects, or identify shapes or colors in the left retinotopic hemifield, but when gazing 30 degrees to the right (so that the left retinotopic field was in the right hemispheric field), he performed nearly as well in the left retinotopic field as in the right. The mechanism of this gaze-dependent hemifield visual impairment is unknown, but we discuss four possibilities: (1) eccentric gaze enhances an alternative visual system; (2) the lesion led to modality-specific hemispheric inattention that was corrected by directing intention (plan to act) and gazing to the right; (3) the lesion led to modality specific inattention that was corrected by compensatory mechanisms that may normally enhance attentive vigilance in central space during eccentric gaze; and (4) the neuronal substrate for hemispheric vision was destroyed, whereas that for retinotopic vision was preserved. PMID- 1866015 TI - Progressive supranuclear palsy: altered sensory processing leads to degraded cognition. AB - We studied the latencies, amplitudes, and scalp distributions of the early and late components of the event-related brain potential (ERP) in patients with progressive supranuclear palsy (PSP) and matched normal controls. In separate choice reaction time (RT) tasks, the subjects pressed buttons to visual stimuli presented randomly at probabilities of either 20/80 or 50/50. Compared with normal controls, PSP patients had significantly reduced amplitudes and increased latencies for both the visual P2 and P300 components at all levels of probability. RTs and percent errors were significantly greater in the patients compared with controls. Neither the amplitude nor latency of the visual N1 component was significantly altered in these patients. There were no significant group differences in the distribution of electrical activity over the scalp for any of these ERP components, a finding which suggests that the neural structures responsible for generating these potentials were intact in these patients. The decreased ERP component amplitudes and increased ERP component latencies, combined with intact scalp distributions and increased RTs and error rates, present a pattern of results suggesting that the stimulus identification or categorization processes in these patients are significantly degraded. PMID- 1866016 TI - Non-Menkes-type copper deficiency with regression, lactic acidosis, and granulocytopenia. AB - A 2-year-old girl with granulocytopenia developed fever followed by truncal ataxia and progressive neurologic regression. CT demonstrated symmetric low density areas in the cerebral white matter. Sural nerve biopsy revealed axonal degeneration. Blood lactate levels were high, and serum levels of copper and ceruloplasmin and urinary excretion of copper were low. Cultured skin fibroblasts showed normal copper uptake. Treatment with oral copper administration normalized serum copper and ceruloplasmin levels, blood lactate levels, and granulocyte count. However, copper levels in the CSF were still low, and the patient showed no clinical improvement. We speculated that copper transport across the intestinal wall and across the blood-brain barrier was impaired. PMID- 1866017 TI - The effects of L-dopa on excessive daytime sleepiness in narcolepsy. AB - We examined the effects of L-dopa on the excessive daytime sleepiness of six narcoleptic patients while using a double-blind design and objective measurements of vigilance. The two treatment periods, L-dopa or placebo, lasted for 2 weeks each, separated by a 1-week washout period. In addition to the standard Multiple Sleep Latency Test (MSLT), two different tests assessed the daytime vigilance: the Analogue Vigilance Scale (AVS) and the Four Choice Reaction Time Test (FCRTT). L-dopa improved vigilance and performance as evaluated by the AVS and the FCRTT, while the capacity to fall asleep rapidly remained unchanged as evaluated by the MSLT. Results of the present study suggest that L-dopa is effective in improving the vigilance level of narcoleptic patients and raises the hypothesis that dopamine may play a role in the physiopathology of excessive daytime sleepiness of this condition. PMID- 1866018 TI - Reorganization of corticospinal pathways following spinal cord injury. AB - To assess changes in the relationship between cortical motor representation areas and their target muscles following spinal cord lesions, we studied motor evoked potentials (MEPs) to transcranial magnetic stimulation in six patients with complete spinal cord injuries at low thoracic levels and eight healthy subjects. Magnetic stimulation at rest activated a larger fraction of the motoneuron pool and evoked MEPs with shorter latencies from a larger number of scalp positions in muscles immediately rostral to the level of a spinal cord injury than in corresponding muscles in controls. The MEPs associated with maximal voluntary activation were not significantly different in the two groups. These results suggest enhanced excitability of motor pathways targeting muscles rostral to the level of a spinal transection, reflecting reorganization of motor pathways either within cortical motor representation areas or at the level of the spinal cord. The data do not allow the determination of the contribution of spinal or cortical mechanisms. However, they support the notion of a limited flexible relationship between primary motor cortex and its target muscles following alterations of normal input-output patterns. PMID- 1866019 TI - Leg paresthesias induced by magnetic brain stimulation in patients with thoracic spinal cord injury. AB - We studied the induction of leg paresthesias by magnetic stimulation of the brain in seven patients with thoracic T9-12 spinal cord injury and in four normal volunteers by delivering transcranial magnetic stimulation over scalp positions 1 cm apart with a Cadwell MES-10 magnetic stimulator and an 8-shaped magnetic coil at 100% stimulus intensity. We asked subjects to report sensations felt after each stimulus. In all normal subjects, magnetic stimulation evoked sensations described as tingling or a wave descending along the leg, usually accompanied by EMG responses in leg muscles. In three of the seven patients, stimulation evoked sensations of tingling, numbness, touch, or a wave descending along the leg, lasting up to 10 seconds and referred to different parts of the legs and toes. In the patients, sensations were felt more distally the closer the site of stimulation was to the midline. Patients with leg paresthesias had less motor reorganization in abdominal muscles than those without paresthesias. These findings suggest that portions of the cortical representation areas for body parts deafferented by a complete spinal cord injury can remain related to those body parts for up to several years. A central origin of these paresthesias is probable. PMID- 1866020 TI - Parental sex effect in familial amyotrophic lateral sclerosis. AB - Since a parental sex effect has been reported in Huntington's disease, we looked to see whether a similar effect is apparent in adult (autosomal dominant) familial ALS. We analyzed the data for 145 patients, with an onset age range of 20 to 68 years and a known affected parent (AP), from 52 families described in the literature. There was a significant increase in the percentage of patients inheriting the gene from an affected mother as a function of the age at onset. There was also a significant correlation between AP and offspring age at onset only when the AP was the mother. PMID- 1866021 TI - A balanced carbohydrate: protein diet in the management of Parkinson's disease. AB - Although restricting dietary protein is a proposed adjunct to treating Parkinson's disease (PD), the effect of carbohydrate consumption is unknown. We measured plasma levodopa and large neutral amino acid (LNAA) levels in nine PD patients treated with carbidopa/levodopa and different isocaloric meals containing high protein-low carbohydrate, low protein-high carbohydrate, and balanced 5:1 carbohydrate:protein mixtures. We found that levodopa levels increased significantly regardless of the type of diet, but that plasma LNAA levels varied less and motor performance was superior after the balanced diet than after the other two meals. We conclude that PD patients can consume nutritionally adequate meals and still maintain a stable plasma levodopa:LNAA ratio. PMID- 1866022 TI - Occurrence of resting tremor in Parkinson's disease. AB - Several previous studies have noted that resting tremor (RT) is absent in 10% to 30% of idiopathic Parkinson's disease (IPD) patients. We report our 22-year observations in 47 pathologically verified parkinsonian patients. In all the IPD cases with median follow-up of 3.7 years, RT was noted on at least one evaluation. Among other parkinsonian syndrome variants characterized by widespread subcortical pathology with median follow-up of 2.86 years, RT was seen in 31% of the cases. Our data indicate that the sites typically involved in IPD are sufficient to produce RT. PMID- 1866023 TI - MRI reveals multiple reversible cerebral lesions in an attack of acute intermittent porphyria. AB - A 20-year-old woman had an attack of acute intermittent porphyria (AIP) with seizures and hallucinations. MRI revealed multiple lesions in both hemispheres. Both the cerebral clinical abnormalities and the MRI lesions resolved following treatment. These findings suggest that a vascular mechanism may underlie the pathogenesis of cerebral dysfunction in AIP. PMID- 1866024 TI - Clinical correlation with serum-soluble interleukin-2 receptor levels in Guillain Barre syndrome. AB - In patients with Guillain-Barre syndrome (GBS) soluble interleukin-2 receptor (sIL-2R) levels were elevated compared with those of patients with other neurologic diseases (OND), and of healthy controls. Smaller increases in sIL-2R levels occurred in OND patients compared to healthy subjects. Monitoring of GBS patients clearly demonstrated that decreases in sIL-2R levels correlated with clinical recovery. Thus, T-cell activation may be relevant in the pathogenesis of GBS. PMID- 1866025 TI - Serotonin uptake in the blood platelets of Alzheimer's disease patients. AB - We determined serotonin (5-HT) uptake in the blood platelets of Alzheimer's disease (AD) patients and comparable age-matched normal controls. The maximum number of 5-HT uptake sites (Vmax) was significantly increased in mild and moderate AD patients, and a trend toward decreased V max was observed in severe AD patients as compared with normal controls. The Km of 5-HT uptake was negatively correlated with the Face-Hand Test (FHT) score of severely ill AD patients, whereas Vmax was correlated with the FHT score and the Mental Status Questionnaire score in the entire AD sample. PMID- 1866026 TI - Theophylline-associated seizures with "therapeutic" or low toxic serum concentrations: risk factors for serious outcome in adults. AB - We report 12 adults with seizures associated with serum theophylline levels between 14 and 35 mg/l. The seizures were frequently prolonged, and outcome was generally poor with eight deaths. Although we did not identify comparable control groups, possible risk factors for serious outcome in theophylline-associated seizures were age, previous brain injury or disease, severe pulmonary disease, and possibly low serum albumin level. In patients with these risk factors, serum theophylline levels should be maintained below 10 to 15 mg/l. PMID- 1866027 TI - Homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency revealed by stroke in adult siblings. AB - Three patients from a single family of six siblings had homocystinemia and homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency and had severe recurrent strokes in adult life. Two of the patients died 1 year after clinical onset. PMID- 1866028 TI - Evidence against the transmissibility of Alzheimer's disease. PMID- 1866029 TI - Conjugal multiple sclerosis: a clinical and laboratory study. PMID- 1866030 TI - Hemifacial spasm associated with Paget's disease of bone: good response to calcitonin. PMID- 1866031 TI - Persistent lumbar aglycorrhachia of unknown cause. PMID- 1866032 TI - Cognitive effects of anticonvulsants. PMID- 1866033 TI - Campylobacter neuropathy. PMID- 1866034 TI - [Heller's extramucosal cardiomyotomy under endoscopic control. The long-term results]. AB - Twenty-five patients underwent Heller cardiomyotomy with Nissen fundoplication, made through an abdominal incision under endoscopic control. Long term results were evaluated according to clinical, radiological, manometric and 24-hour esophageal pH-metric studies. Clinical results were excellent in 44% of the patients, good in 40%, fair in 4% and bad in 12%. The four unsatisfactory results are due to recurrence of dysphagia in one case and to appearance of GER in the others. Postoperative X-ray controls and manometric tests showed a significative decrease in the esophageal diameter, in resting and post swallowing LES and esophageal body pressure. The 24-hour pH test showed an abnormal percentage of time with pH less than 4 in two patients, and a direct connection with clinical and endoscopic results. Endoscopic control of myotomy allows us to define precisely the extension of the functional stenosis and to eliminate completely the dysphagia. In the postoperative evaluation the 24-hour pH monitoring allows an early identification of GER, and the prevention of possible complications even in the absence of any clinical sign. PMID- 1866035 TI - [The surgical treatment of gastric cancer. A review of the results and a comparison with Japanese experience]. AB - The authors synthetize the principal trends about surgical treatment of gastric cancer underlining the actual way. Then, is considered the Japanese experience whose results are compared with those in the west to try an explanation of surgical data amply in favour of resected in Japan. PMID- 1866036 TI - [Pancreatic pseudocysts. An important surgical problem]. AB - The pancreatic pseudocyst is a serious complication of acute or chronic pancreatitis. Surgical internal anastomosis can be an adequate solution to this problem. Sixty patients with pancreatic pseudocyst have been referred to our institution in the last 15 years; 47 of them were operated upon. Different techniques were employed according to differences in the pseudocyst wall status and the presence or absence of infection. PMID- 1866037 TI - [Internal pancreatic fistulae. The authors' experience]. AB - The paper describes the authors' personal experience of internal pancreatic fistulas. This is an uncommon pathology which should however be taken into account in the presence of ascites or pleural effusion without a clear cause. Essential diagnostic tests are chemical and physical examination and the assay of amylase in ascitic or pleural fluids. Medical treatment is sometimes efficient leading to the disappearance of the fistula. If medical therapy fails, surgery is necessary, based on pancreatic resection or the drainage of the cyst or interrupted pancreatic duct. PMID- 1866038 TI - [The diagnosis and therapy of recurrent tumor of the rectum]. AB - The authors review the pathogenesis of locoregional recurrences of rectal cancer, pointing out clues for the diagnosis and staging of the disease which are valuable for the definition of a treatment strategy. Surgery is the mainstay of any attempt to cure those recurrences that are amenable to radical resection; over and above the diagnostic role of second-look laparotomy in suspected cases, surgery must include those measures able to reduce actinic damage whenever postoperative radiotherapy is required. On the other hand, palliative surgery is necessary to resolve the presence of intestinal obstruction, fistulous tract, or the removal of abscess and necrotic tissue. In these cases, the quality of life seems to be the prime factor in the choice of therapy (radiotherapy, loco regional or systemic chemotherapy, hyperthermia). PMID- 1866039 TI - [The management of head trauma in a general surgery department. a contribution to an epidemiological analysis]. AB - Personal experience in the management of head injury in a General Surgery Department is reported and a series of 352 patients analysed with a view to identifying variations in the epidemiological profile of this pathology over the last decade and in order to establish indications for admission and the transfer of the patient to specialist departments. PMID- 1866040 TI - [A mucinous cystadenocarcinoma of the pancreas. A clinical and histopathological contribution]. AB - Two cases of pancreatic cystadenocarcinoma, a very rare pathology, are reported. The authors treat the anatomopathological classification and they underline the diagnosis especially with reference to the new methods of cytologic study. Finally they consider the surgical approach that must be radical because of the potential malignancy of this kind of tumor whose prognosis is quite good with a lasting long-term survival. PMID- 1866041 TI - [Submucosal lipomas of the cecum. A case report]. AB - The paper reports a case of submucous lipoma of the cecum. The difficulty of clinical diagnosis is underlined on account of aspecific symptoms, and in fact it is uncommon for diagnosis to be made on the basis of X-rays. Colonoscopy, in particular using bioptic techniques, allows the nature of the lipoma to be diagnosed, and in addition may act as an excellent therapeutic instrument. PMID- 1866042 TI - Minimal change nephrotic syndrome associated with Hodgkin's lymphoma. AB - This report documents the occurrence of minimal-change nephropathy in four patients with Hodgkin's disease. In two cases the onset of the nephrotic syndrome antedated the recognition of lymphoma by 4 and 7 years respectively, while in the other two the nephrotic syndrome manifested 5.5 years and 13 months respectively after lymphoma. In all cases, the nephrotic syndrome resolved when therapy was effective in treating active Hodgkin's disease. The significance of minimal change nephropathy in association with Hodgkin's disease is discussed. It may be that abnormalities in T-cell function lead to minimal-change nephropathy in some patients with certain forms of Hodgkin's disease. PMID- 1866043 TI - Flexible urethrocystoscopy in nephrological investigation. AB - Flexible urethrocystoscopy under local anaesthetic was performed on 100 patients as part of their nephrological investigations. This was carried out by a nephrologist, obviating the previous practice of referral to a surgical colleague for rigid instrumentation under general anaesthetic. A pathological diagnosis was made in 69 patients with flexible urethrocystoscopy alone; 17 patients required subsequent rigid cystoscopy to obtain or confirm a diagnosis. Thirty-four patients had normal examinations and of these 13 underwent renal biopsy for diagnosis. Considerable savings in theatre time, man-hours and anaesthetic risk to the patients were made without compromising diagnostic accuracy or patient wellbeing. PMID- 1866044 TI - Calcium metabolism in early chronic renal failure: implications for the pathogenesis of hyperparathyroidism. AB - Studies in the past showed elevated immunoreactive parathyroid hormone (PTH) serum values in early renal failure, but the assays used in these studies could not discriminate between bioinactive fragments of the PTH peptide and biologically active hormone. The availability of a sensitive PTH assay, which quantitates intact hormone, now allows the analysis of biologically active PTH in renal failure. To characterise more precisely the point of onset of hyperparathyroidism in the course of chronic renal failure and its relation to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], we measured plasma intact PTH and vitamin D metabolite serum values in 63 non-nephrotic uraemic patients (male n = 35, female n = 28, age 31-78 years) with incipient (GFR 60-90 ml/min per 1.73 m3, n = 19) mild (GFR 40-60, n = 22) and moderate (GFR 20-40, n = 22) renal failure, and in 22 age-matched healthy control subjects. Intact PTH concentrations were negatively correlated with GFR (r = -0.57, P less than 0.001). Median plasma intact PTH values (normal range 1.2-6 pmol/l) were 5.6 (range 2.2-13.0) in incipient, 8.1 (2.9-24.0) in mild, and 13.0 (5.4-59.0) in moderate renal failure. Intact PTH values in incipient renal failure were significantly greater than in 22 age-matched control subjects (P less than 0.01). The decline of GFR was paralleled by a progressive decrease in 1,25(OH)2D3 serum values (r = 0.44, P = 0.001). Median values of the hormone (normal range 35-90 pg/ml) were 32 (range 20 66) in incipient (P less than 0.01 vs. age-matched control subjects), 34 (22-74) in mild, and 26 (17-39) in moderate renal failure. In all three groups, mean serum phosphate and total calcium concentrations (corrected for serum protein) were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866045 TI - The treatment of uraemic hyperphosphataemia with calcium acetate and calcium carbonate: a comparative study. AB - A comparative study of long-term haemodialysis patients investigated the effects of calcium acetate and calcium carbonate on concentrations of serum phosphate, calcium, and parathyroid hormone. It was demonstrated that both substances led to a significant decrease in phosphate and serum parathyroid hormone. Administration of calcium acetate reduced the serum phosphate concentration in 7 weeks from an initial value of 2.08 +/- 0.53 mmol/l to 1.51 +/- 0.39 mmol/l (P less than 0.01). Following a 1-week wash-out period, calcium carbonate reduced the serum phosphate concentration in the same patients from 1.99 +/- 0.62 mmol/l to 1.34 +/- 0.40 mmol/l (P less than 0.01). Of particular significance, however, is the fact that in relation to daily elementary calcium intake, calcium acetate was a considerably more effective binder of intestinal phosphate than calcium carbonate. During administration of calcium acetate only 1.02 g of elementary calcium were required daily in order to reduce the serum phosphate concentration. The same patients, however, required 1.88 g of elementary calcium during calcium carbonate therapy. Complementary studies investigated the influence of an accompanying calcitriol medication. In this instance, too, calcium acetate was shown to be more effective; although the patients developed hypercalcaemia with calcium acetate, this happened more often with calcium carbonate. In summary it can be said that daily calcium loading of the uraemic organism under calcium acetate therapy is reduced by nearly half as compared to calcium carbonate therapy, and that this can be achieved with the same effective decrease of the serum phosphate concentration. PMID- 1866046 TI - Reoperation for secondary hyperparathyroidism in chronic renal failure. AB - From 1972 to 1987, 112 parathyroidectomy (PTX) operations were carried out in 105 haemodialysis or transplant patients by the same surgeon. Twelve had to be reoperated on (19 operations in all) for persistent (9 cases) or recurrent (3 cases) hyperparathyroidism. In six patients morphological tests (echography and technetium-thallium scintigraphy) contributed usefully by detecting parathyroid masses. Repeated surgery was finally effective in nine cases. PMID- 1866047 TI - Theoretical approach and clinical application of kinetic modelling in dialysis. AB - Using kinetic modelling for shaping profile dialysis, we present a promising approach to improve the cardiovascular stability of patients during dialysis treatment. In order to obtain an insight into the physiological mechanisms of increased stability, a model considering alterations of electrolytes and water distribution and of acid-base status was developed. This algorithm was used for the evaluation of 114 dialysis sessions, which were performed with highly individualised profiles. Each profile was developed for one patient by trying empirically to prevent episodes of hypotension as well as other clinical problems throughout dialysis. The main advantage of profile dialysis compared to standard bicarbonate dialysis, for example, is a reduced water influx into the cell during the treatment. According to our clinical and theoretical results a correlation between water influx into the cell and time of occurrence of hypotensive episodes in individuals can be assumed. Hypotension usually starts after 0.5 litres of water have entered the intracellular space, regardless of the time necessary for this fluid shift. PMID- 1866048 TI - Effect of intraperitoneal administration of two different batches of albumin solutions on peritoneal solute transport in CAPD patients. AB - The effects of intraperitoneal administration of two different batches of human albumin (batch A and batch B) on peritoneal solute transport and dialysate white cell count were studied in 16 CAPD patients. The studies were done on two separate days during a 4-h dwell, one day without and one day with the intraperitoneal administration of 10 g/l human albumin. Marked differences were found between the two batches. The transport of all measured solutes increased during administration of batch A compared to the control experiments: urea 78% +/ 62%, lactate 51% +/- 38%, creatinine 96% +/- 54%, glucose 67% +/- 55%, inulin 27% +/- 33% IgG 126% +/- 80%, mean +/- SD; P less than 0.02). In the experiments with batch A the white cell count of the test bag was greater than that of the effluent ('night bag') before the test (13 +/- 5 vs 194 +/- 61 mm3/l; P less than 0.02). These effects were also observed when the dialysate was buffered to pH = 7.4 before inflow. Albumin batch B showed no effect on solute transport and white cell count. The effects of solute transport and white cell count are probably caused by the greater concentration of prekallikrein activator in batch A when compared to batch B (30.1 vs 0 U/l). Caution is warranted when human albumin is used for simultaneous measurement of peritoneal fluid and solute kinetics. PMID- 1866049 TI - Streptokinase in the treatment of innominate-vein thrombosis in association with haemodialysis catheter. Preservation of a precious arteriovenous fistula. PMID- 1866050 TI - Disseminated infection of the central nervous system caused by Nocardia farcinica. PMID- 1866051 TI - Is chronic peritoneal dialysis safe in patients with intra-abdominal prosthetic vascular grafts? PMID- 1866052 TI - Nephrotic syndrome in ulcerative colitis. PMID- 1866053 TI - Wegener's granulomatosis presenting as granular gingivitis. PMID- 1866054 TI - Biocompatibility of haemodialysis systems: present and future. Vienna, 9 September 1990. PMID- 1866055 TI - Introducing the biology of bioincompatibility in dialysis. PMID- 1866056 TI - Recent advances in the biocompatibility of haemodialysis membranes. PMID- 1866057 TI - Ionised calcium changes and parathyroid hormone secretion in haemodiafiltration in relation to substitution fluid calcium content. AB - This study was carried out to evaluate the acute effect of either 1.75 mmol/l calcium (A-HDF) or bicarbonate-containing and calcium-free (B-HDF) substitution fluid on calcium balance, serum ionised calcium, and intact parathyroid hormone (PTH) during haemodiafiltration (HDF: 1.3 m2 polysulphone dialyser; blood flow rate, 400 ml/min; treatment time 210 min; substitution fluid volume, 10 litres; dialysate calcium, 1.75 mmol/l). During A-HDF calcium balance was slightly positive (1.47 +/- 2.95 mmol), serum ionised calcium increased from 1.24 +/- 0.08 mmol/l to a final 1.46 +/- 0.05 mmol/l at the end of the treatment (P less than 0.001), and PTH decreased from 227 +/- 231 pg/ml to 150 +/- 123 pg/ml (P less than 0.01), during B-HDF calcium balance was negative (-3.06 +/- 1.3 mmol), ionised calcium decreased from 1.29 +/- 0.05 to 1.24 +/- 0.05 mmol/l (P less than 0.05) without inducing a statistically significant increase in PTH. However, in some patients the increase in PTH after treatment was greater than 50%. When the ultrafiltration rate was increased to 75-100 ml/min and bicarbonate-containing and calcium-free replacement fluid was used (B2-HDF), calcium balance became more negative (-9.75 +/- 4.55 mmol) and the decrease of ionised calcium was greater (from 1.3 +/- 0.06 to 1.14 +/- 0.04 mmol/l, P less than 0.01) inducing a significant increase of PTH (from 297 +/- 366 to 443 +/- 518 pg/ml, P less than 0.01). PTH changes were negatively correlated (r = -0.85) to ionised calcium changes during the treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866058 TI - Phosphate kinetics in dialysis patients. AB - During extrarenal therapy, plasma phosphate concentrations have specific kinetics: plasma values reach a steady-state nadir 90-120 min after the beginning of the session (from 0.6 to 1.1 mmol/l) with a subsequent high rebound in the 3-4 h following the session. These kinetics are found during haemofiltration (HF) with high ultrafiltration (UF) rates (greater than 270 ml/min) and UF volumes (greater than 30 1). Other HF studies with different UF rates (100 or 200 ml/min) show that delayed mass transfer cannot explain kinetics which result from a phosphate transfer from cellular to extracellular space. Acetate or bicarbonate reinjection fluid does not modify phosphate kinetics. Immediate decrease of ionised calcium after the session argues against a mobilisation from the exchangeable phosphate pool of bone. Only potassium shows a similar pattern to phosphate, so the hypothesis of a relation between cellular phosphate and potassium fluxes is postulated. 31P-NMR study during and after HF does not allow us to specify phosphate transfer from the cell, but various potassium concentrations in the reinjection fluid (0, 2, 3.5, or 4 mmol/l) confirm the influence of potassium removal on phosphate transfer, and a significant linear relationship can be established between cellular potassium and phosphate fluxes. The influence of phosphate removal on phosphataemia has also been investigated using 0, 2, or 3 mmol/l phosphate in the reinjection fluid. Whatever the phosphate modification achieved by the session, the patient's phosphate concentrations are not significantly different 2 days later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866059 TI - Phosphate removal rate: a comparative study of five high-flux dialysers. PMID- 1866060 TI - Anaemia in high-efficiency dialysis. PMID- 1866061 TI - Recombinant human erythropoietin expressed in C-127 mouse cells: efficacy, side effects and cardiovascular actions. PMID- 1866062 TI - Cytokine production by monocytes during haemodialysis. AB - In order to follow the effect of haemodialysis on monocyte function, we measured the release of interleukin-1 beta (Il-1), interleukin-6 (Il-6), and tumour necrosis factor alpha (TNF alpha) from cultured monocytes isolated before and after dialysis. Monocytes obtained from patients before dialysis released smaller amounts of cytokines than cells from healthy controls. The choice of the dialysis membrane had no effect on predialytic monocyte activity. Basal cytokine release after dialysis remained virtually unchanged, irrespective of the membrane material used. When stimulated with LPS, cells significantly produced more cytokines than under basal conditions. Stimulated monocytes isolated before dialysis produced considerably more cytokines than cells obtained at the end of the dialysis. Taken together, uraemia by itself seemed to depress monocyte activity. Haemodialysis either with cuprophan or PMMA dialysers had no influence on basal cytokine release during a 24-h period following dialysis. Uraemic monocytes, however, appeared to be primed, since stimulation with LPS in vitro caused a more pronounced release of cytokines than in healthy volunteers. PMID- 1866064 TI - Leukocyte-derived mediators and biocompatibility. PMID- 1866063 TI - Involvement of peripheral blood monocytes in haemodialysis: in vivo induction of tumour necrosis factor alpha, interleukin 6 and beta 2-microglobulin. AB - Our aim was to evaluate the role of three different variables in the activation of the monocyte system: dialysis membrane (cuprophane or polyacrylonitrile), dialysate (acetate or bicarbonate), and procedure (standard or high-flux haemodialysis). By ELISA test we measured the 'in vivo' intracellular (monocyte associated) production and extracellular release of tumour necrosis factor alpha (TNF alpha), interleukin-6 (Il-6) and beta 2-microglobulin (beta 2-M) by monocytes from 20 uraemic patients before and after the dialysis session. At the beginning of the dialysis session, uraemic patients' cultured monocytes spontaneously released a greater amount of TNF alpha, Il-6 and beta 2-M compared to normal controls. However, no differences in cytokine and beta 2-M were observed in monocyte lysate between the two groups. At the end of the dialysis session, cultured monocytes from patients treated with cellulosic membranes and acetate dialysate showed greater TNF alpha values than normal controls (P less than 0.001 and P less than 0.05 respectively). Moreover, TNF alpha and Il-6 values were strictly correlated (P less than 0.05). These results clearly show an activation of the monocyte system in uraemic patients undergoing periodic haemodialysis. The implicated factors may be multiple, such as complement activating cellulosic membranes or acetate dialysate. The production of TNF alpha, Il-6 and beta 2-M may explain some of the pathological findings observed in long-term haemodialysis patients. PMID- 1866065 TI - Flow cytometric analysis of leukocytes eluted from haemodialysers. AB - The cellular immune system is impaired in uraemic and haemodialysed patients. We describe a method of studying leukocytes eluted from dialysers at the end of the dialysis session, and we have studied five haemodialysers: cuprophane (CU), cellulose acetate (CA), polymethylemethacrylate (PMMA), polyacrylonitrile (PN), and polysulphone (PS). The analysis was performed by flow cytofluorimetry using monoclonal antibodies. The absolute number of eluted leukocytes was rather elevated, ranging from 88 (CU) to 9 (PS) millions of cells. When compared to peripheral blood values, the percentage analysis revealed an increase of PMN and monocytes and a decrease of lymphocytes. A relative increase of B lymphocytes was observed in all filters studied. A trapping of T lymphocytes (PAN) and a minor increase of NK cells (PMMA, PS, CA) were also observed. The elution of leukocytes from dialysers may be helpful in evaluating the biocompatibility of membranes for haemodialysis. PMID- 1866066 TI - In vitro platelet adhesion to dialysis membranes. AB - This work describes an in vitro system developed to quantitate platelet deposition on different dialysis membranes. The system is based on the use of small dialysis filters and reproduces the haemodynamic pattern of blood flowing through hollow fibres during in vivo dialysis. We have determined the in vitro platelet adhesion to cuprophan and to a non-cellulosic membrane, polymethylmethacrylate. When albumin concentration in the platelet suspension was low (0.35%) platelet deposition to cuprophan and to polymethylmethacrylate was comparable. When albumin concentration was increased to a physiological value (3.5%) platelet adhesion to both cuprophan and to polymethylmethacrylate membranes significantly decreased. This effect of albumin was greatest for the high-permeable polymethylmethacrylate membrane (BK). These data suggest that platelet membrane interaction is significantly influenced by circulating albumin. PMID- 1866067 TI - Cellular immunology in regular dialysis: a biological model for biocompatibility evaluation. AB - Cellular immunity represents an interesting biological model for biocompatibility evaluation of artificial materials owing to its sensitivity to contact with the external environment and its capability of modulating response reactions to foreign agents. Advanced methodologies such as flow cytometry and the immunoenzyme techniques in particular have given new insights into lymphocyte structure and functions, enabling analysis of the in vivo modification of these cells. By means of these sophisticated techniques we investigated lymphocyte activation and proliferation during one single haemodialysis session. Findings clearly show that increases in HLA antigen density (class I and II), DNA synthesis, and interleukin-2 receptor serum concentration (Il-2R) take place during the dialysis procedure, and reach their maximum during the first hour of extracorporeal circulation. The relationship between dialysis procedure and cellular immunity appears noticeable and is of potential value in the evaluation and quantification of the biocompatibility of different dialysis membranes. PMID- 1866068 TI - Development of a new antithrombogenic continuous ultrafiltration system (ACUS) and its clinical evaluation. AB - A new totally antithrombogenic continuous ultrafiltration system (ACUS), consisting of polyacrylonitrile-polyethyleneoxide (PAN-PEO) membrane and ionically heparin-bound catheter, tubing, and module header was designed and its performance was confirmed through animal experiments and clinical evaluation. Animal experiments revealed that persistent antithrombogenicity and maintained ultrafiltration without systemic heparinisation were observed only when the three major parts--i.e. (1) the catheter and tubing, (2) the header part of a haemofilter module, and (3) the fibre membrane--were all antithrombogenic and connected to each other without uneven structures. ACUS was clinically applied to 15 oliguric patients with various severe conditions. We found that one filter could function for approximately 26 h without systemic anticoagulation, even in the presence of low blood pressure, and that ACUS did not change platelet function. Thus, ACUS seems to be very suitable for the management of volume overload, especially in patients with severe circulatory problems or bleeding tendencies. PMID- 1866069 TI - Biocompatibility of dialysis membranes: a comparative study. AB - White blood cell counts and plasma C5a anaphylatoxin values were studied during haemodialysis with cuprophane, ethylenevinylalcohol, polycarbonate, polymethylmethacrylate, acrylonitrile, polysulphone and polyacrylonitrile membrane dialysers. Cuprophane induced marked leukopenia with striking plasma generation of C5a. Ethylenevinylalcohol, polycarbonate, polymethylmethacrylate and acrylonitrile promoted an intermediate degree of leukopenia with mild but significant complement activation; however, leukopenia and C5a generation were not time-related with some of these membranes. In contrast, polysulphone and polyacrylonitrile showed neither leukopenia nor C5a increase. These data suggest that although there must be further factors involved, complement-derived anaphylatoxin C5a generation may have a relevant role in the mechanism of haemodialysis-induced leukopenia. At the present time evaluation of the leukopenic effect and the C5a generation capability of a membrane seem worthwhile for estimating its degree of biocompatibility. PMID- 1866070 TI - Biocompatibility of dialyser membranes: roles of membranes and of patients. PMID- 1866071 TI - Long-term influence of dialysis treatment on beta 2-microglobulin, interleukin-2 R and tumour necrosis factor. AB - Recently much interest has been focused on the phenomena produced by the interaction between blood and dialytic membranes. The aim of this study was to evaluate beta 2-M, Il-2 and TNF changes in relation to the long-term use of different membranes (CU, PAN-AN69, PMMA, PS) and different dialytic treatments (HD, HDF, AFB). Plasma beta 2-M was significantly increased in patients dialysed with CU compared to synthetic membranes, and decreased in AFB compared to HD and HDF. Intradialytic changes of beta 2-M, corrected for haemoconcentration, resulted in a significant increase with CU and PMMA, while a decrease was found with PAN-AN69 and PS and during convective treatments, more evident during haemofiltration performed with sterile dialysate without acetate. I1-2R was increased in all patients compared to normal subjects, without any intradialytic change, regardless of the type of membrane used. TNF was in the normal range. The different decrease of beta 2-M observed with synthetic membranes, the stable intradialysis I1-2 R values during HD performed with membranes non-permeable to endotoxins and during AFB, and the absence of detectable TNF support the hypothesis that dialysate plays an important role in activating beta 2-M and cytokines, together with other factors. PMID- 1866072 TI - The role of adsorption in beta 2-microglobulin removal. AB - BK-PMMA 2.1 m2 surface dialysers were used in vivo and in vitro for evaluation of their capacity for beta 2-M removal by both adsorption and elimination through the membrane. As expected, in vivo, beta 2-M plasma concentrations were more effectively reduced when the dialyser was used in haemofiltration, rather than in haemodialysis. However, the mass recovered in the ultrafiltrate could not account for the observed difference in beta 2-M removal. In vitro tests demonstrated that membrane adsorption of beta 2-M is greater when the dialyser is used in convection than in diffusion. Therefore, the greater beta 2-M removal during haemofiltration depends on both increased adsorption and membrane elimination by convection. Thanks to adsorption, beta 2-M removal by haemodialysis was greater than for other synthetic membranes, but was insufficient to obtain beta 2-M removal corresponding to the estimated generation. PMID- 1866073 TI - Long-term multicentre study on beta 2-microglobulin removal by PMMA BK membrane. AB - A long-term multi-centre clinical study was performed, based upon our first identification of beta 2-microglobulin (beta 2-M) amyloid fibrils and optimisation of the pore-size of the polymethylmethacrylate (PMMA) membrane for its removal. To clarify the clinical significance of the newly designed PMMA membrane, BK membrane, having an average pore radius of 70-80 Angstroms (7-8 nm), a total of 73 chronic haemodialysis patients from 28 centres, classified into four groups, were studied. Although the plasma beta 2-M decreased in all groups through the continued use of BK membrane, the early introduction of haemodialysis with BK membrane reduced the plasma concentration of this substance more than in the case of the later introduction. Pain index, defined as the total pain score divided by the number of painful joints, decreased significantly over the period of haemodialysis duration with BK membrane. This suggests that the continued use of BK membrane from the early phase of haemodialysis treatment results in the amelioration and/or prevention of joint pains of haemodialysis patients as well as preventing the increase in plasma beta 2-M. PMID- 1866074 TI - High-flux acetate haemodialysis: a single-centre experience. AB - One hundred haemodialysed patients have been treated for 4 h thrice weekly by acetate haemodialysis with high-flux dialysers (HAHD) 1.4-1.8 m2 and automated ultrafiltration control for 18.9 +/- 8.3 months. The aim of the study was to evaluate the efficacy of treatment as regards urea and beta 2-microglobulin removal, cardiovascular stability, acid-base balance and plasma Il-1 variations. Moreover medium-term observation of both lipid profile and basal beta 2 microglobulin concentrations were performed. With our current adequacy criteria (urea clearance greater than or equal to 120 l/week; KT/V greater than or equal to 1.2; beta 2-microglobulin removal greater than or equal to 150 mg/treatment), the occurrence of hypotension was 6% during 24,500 treatments. Cardiovascular stability was preserved by the increase of total peripheral resistances in response to cardiac output decrease. No disturbances of acid-base parameters were observed in spite of plasma acetate concentrations greater than 6 mmol/l. No variations of plasma Il-1 occurred during the session or 2 h later. PMID- 1866075 TI - Haemodiafiltration versus paired filtration dialysis: evaluation of in vivo solute removal. PMID- 1866076 TI - Biocompatibility of PMMA membranes used in haemofiltration and haemodiafiltration: beta 2-microglobulin removal and release of granulocyte elastase. PMID- 1866077 TI - Biocompatibility and capability of haemopurification systems: review and future development. AB - Past, present, and future developments of haemopurification systems are reviewed with respect to their biocompatibility and functional capability. The history of the polymethylmethacrylate (PMMA) membrane is introduced, along with the modifications aimed at removing beta 2-microglobulin (beta 2-M). A highly permeable PMMA membrane (BK) has the capability to adsorb beta 2-M. We have succeeded in finding material, thought to be beta 2-M, in transmission electron microscopy of the membrane perfused with plasma from haemodialysis patients. As examples of the future development of haemopurification systems to remove targeted substances more specifically and efficiently, we consider hybridised bioartificial kidney containing proximal renal tubular cells fixed on collagen hollow fibre for degradation of beta 2-M to aminoacids, and an artificial reticuloendothelial system with polymyxin B immobilised fibre for removing endotoxin in blood. Targeting and specific removal with prepared biocompatible materials will open the way to the development of the second generation systems and close collaboration between medicine and industry is essential for realising these goals. PMID- 1866078 TI - Beta 2 microglobulin-related amyloidosis causing atlantoaxial spondylarthropathy with spinal-cord compression in haemodialysis patients: detection by MRI. AB - Bone destruction due to beta-2 microglobulin (beta 2-M)-related amyloid deposition is becoming more frequently observed in long-term haemodialysis patients. We report five cases in an unusual site, the upper cervical spine. All patients had been on haemodialysis for more than 13 years and presented with progressive spinal-cord involvement in the region of the first and second cervical nerves. While conventional X-rays and CT scans showed only minor vertebral destruction, MRI disclosed a tumour-like mass within the upper spinal canal, best seen with long TR gradient recalled images. One patient required urgent surgical intervention because of severe spinal-cord compression, and the material was shown to be typically beta 2-M-related amyloid. PMID- 1866079 TI - Interleukin-6 production of uraemic haemodialysed patients: effects of different membranes. AB - Interleukin-6 (Il-6) has a complex spectrum of biological activities (growth and differentiation of B cells and synthesis of acute-phase proteins by liver). To evaluate the role of this cytokine in the inflammatory response induced by blood interaction with haemodialysis membranes, we have investigated Il-6 synthesis and release in supernatant of 24-h cultured peripheral blood mononuclear cells (PBMC) isolated from ten haemodialysed patients and eight healthy control subjects. In haemodialysed patients, blood samples were drawn before and after their usual dialytic treatment with cuprophane membranes and following 1 and 2 months with polymethylmethacrylate (PMMA) membranes. Il-6 was determined by 72-h incubation of serial dilutions of PBMC supernatant with Il-6-dependent cell line 7TD1; dilutions of rIl-6 were included as standard. Compared to Il-6 synthesis in control subjects (3.3 +/- 2.8 U/ml) the patients usually haemodialysed with cuprophane membranes showed significantly greater values (9.8 +/- 4.5 U/ml, P less than 0.02 before the treatment, and 10.4 +/- 6.1 U/ml, P less than 0.05 after the treatment). A significant reduction, in comparison with the values obtained with cuprophane membranes, was obtained after 1 month (5.3 +/- 2 U/ml, P less than 0.02 before the treatment, and 7.5 +/- 6 U/ml after the treatment) and especially after 2 months (3.4 +/- 3.2 U/ml, P less than 0.02 before the treatment, and 4.4 +/- 3.4 U/ml, P less than 0.05 after the treatment) of dialysis with PMMA membranes. In conclusion, our results show increased Il-6 production in haemodialysed patients usually treated with cuprophane membranes, suggesting a chronic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866080 TI - Long-term observation on renal-osteodystrophy-related parameters in dialysis patients. AB - Among chronic haemodialysis patients, renal osteodystrophy is one of the most serious long-term complications which should be solved for substantially improving the quality of their lives. However, due to its multifactorial mechanism and the difficulty of its diagnosis, a final protocol to ameliorate and/or prevent renal osteodystrophy is difficult to establish. To discover any clues to a solution, we performed long-term observations on renal osteodystrophy related parameters in chronic haemodialysis patients over 9 years, starting in 1980, focusing mainly on X-ray photodensitometry. Taking into consideration changes of treatments prescribed and/or tried during this period, changes of renal osteodystrophy-related parameters including metacarpal index, bone mineral content, and bone index were periodically monitored. While bone mineral content and bone index deteriorated for patients who were commenced on haemodialysis in 1980, during the consecutive 4 years, bone mineral content was significantly improved, with maintained bone index during the last 4 years for patients started on haemodialysis in 1985. Thirty-one male and thirteen female patients, monitored throughout the 9 years, showed a significant increase in bone mineral content during the past 4 years. The combined effects of current modality such as bicarbonate dialysate, active vitamin D3 and removal of accumulated aluminium, are suggested explanations. PMID- 1866081 TI - Postischemic spontaneous hyperthermia is not a major aggravating factor for neuronal damage following repeated brief cerebral ischemia in the gerbil. AB - Brief and non-lethal cerebral ischemia produces most severe neuronal damage when such ischemia is induced repeatedly at 1-h intervals. We examined whether spontaneous postischemic hyperthermia is an aggravating factor for the cumulative damage following repeated ischemia in the gerbil. We maintained body and cranial temperature at normothermia throughout the initial reperfusion period, but could not observe an amelioration of histopathological brain damage following two 2-min bilateral carotid artery occlusions at a 1-h interval as compared to hyperthermic conditions. The results suggest that postischemic hyperthermia is not a major aggravating factor for the cumulative damage following repeated ischemic insults. PMID- 1866082 TI - Refining the temporal definition of an association at the neuronal level using long-term potentiation and long-term depression in the dentate gyrus. AB - This study sharpens the temporal definition of an association in the context of long-term synaptic modification of the monosynaptic projections from entorhinal cortex to dentate gyrus in the anesthetized rat. The ipsilateral projection produces a powerful postsynaptic excitation and shows synaptic potentiation following 7.5 ms trains. On the other hand, brief, high-frequency contralateral stimulation just after this powerful postsynaptic excitation is followed by long term depression (LTD) at the synapses of this pathway. Therefore, based on the differential induction of long-term potentiation (LTP) or LTD, a cell can distinguish associated pre- and postsynaptic activation at a temporal resolution at least as small as 7.5 ms. PMID- 1866083 TI - Glutamate exocytosis evoked by 4-aminopyridine is inhibited by free fatty acids released from rat cerebrocortical synaptosomes. AB - The Ca(2+)-dependent release of glutamate induced by 4-aminopyridine (4-AP) in rat cerebral cortical synaptosomes was reduced by removal of bovine serum albumin (BSA) from the incubation medium. The decrease in the glutamate release in the absence of BSA was consistent with a reduction in the rise in cytosolic free [Ca2+] after depolarization with 4-AP. Contrarily, neither the glutamate release nor the elevation in cytosolic free [Ca2+] after depolarization with 30 mM KCl was altered by the removal of BSA. The inhibitory action of the free fatty acids released during the incubation of synaptosomes was also observed when exogenous free fatty acids were added to the medium in the presence of BSA. The highest inhibition of 4-AP-induced release of glutamate was observed in the presence of arachidonic acid. The results strongly suggest an inhibitory action of free fatty acids by decreasing Ca2+ entry and glutamate release in rat cerebrocortical synaptosomes. PMID- 1866084 TI - Neonatal striatal NADPH-diaphorase neurons are vulnerable to quisqualate and its analogue alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA). AB - A small population of neurons in the mammalian striatum and cerebral cortex contain NADPH-diaphorase. Recently, this class of neurons has been found in vitro to be selectively vulnerable to low concentrations of non-N-methyl-D-aspartate (NMDA) glutamate agonists. To determine if this pattern exists in vivo, we injected either quisqualate (QA) or its inotropic site analogue alpha-amino-3 hydroxy-5-methyl-4-isoxazole proprionate (AMPA) into the striatum of neonatal rat pups and found a dose-dependent loss of NADPH-diaphorase reactive neurons. These data suggest that the QA receptor may be present and functional at postnatal day 7 when other glutamate receptor subtypes have not yet fully developed and that QA is working through its inotropic site since AMPA causes the same dose-dependent cell death. PMID- 1866085 TI - Generation of developmental patterns in the neuroepithelium of the developing mammalian eye: the pigment epithelium of the eye. AB - Culture experiments with eye anlages of mouse embryos were performed to study developmental traits of the neuroepithelial cells of the prospective pigment epithelium in the eye anlage of pigmented mice. Between the neural plate stage on embryonic day 8 (ED 8, developmental stage 12) and the neural tube stage on embryonic day 9 1/2 (stage 15), the cultured neuroepithelium of the eye generated neurons and glia, identified by morphological and immunocytochemical evidence, but no pigmented cells. In contrast, eye anlages did produce pigment epithelium when cultured in their natural position in a head tissue fragment. A minority of developing neurons displayed tyrosine hydroxylase immunoreactivity, whereas GABAergic, serotoninergic and substance P-ergic neurons, which are common in the mature neuroretina, were not observed. When neuroepithelial cells from embryonic eyes older than stage 15 (ED 9 1/2) were cultured, they differentiated into pigment cells but not into nerve cells or glia. This developmental sequence indicates that the pigment cells derive from the neural lineage. Pigment cell fate dominates over the neural fate beginning at about stage 15 (ED 9 1/2-10). That is at least 2 days before the pigment cell phenotype becomes apparent in vivo (ED 11 1/2-12). PMID- 1866086 TI - Analgesic effects of centrally administered aminoglycoside antibiotics in mice. AB - The possible analgesic effects of i.c.v. administration of several aminoglycoside antibiotics were evaluated in mice using hot plate and tail flick tests. Neomycin (10-80 micrograms/mouse), gentamicin (40-160 micrograms/mouse) and kanamycin (80 320 micrograms/mouse) produced dose-dependent increases in the latencies to forepaw licking and jumping in hot plate test. These drugs also produced dose dependent increases in the percentage of animals showing analgesia in tail flick test. The order of potency of these aminoglycoside antibiotics in both tests was neomycin greater than gentamicin greater than kanamycin, which is exactly the same order that these drugs show as N-type calcium channel blockers. Bearing in mind this fact and the well known analgesic activity of several drugs which decrease neuronal calcium availability, we suggest that the mechanism of aminoglycoside-induced antinociception may be related to the capacity of these antibiotics to block N-type calcium channels and decrease neuronal calcium availability. PMID- 1866087 TI - Compensation of human stance perturbations: selection of the appropriate electromyographic pattern. AB - Perturbations of stance evoke purposive EMG patterns which are directed to hold the body's centre of gravity over the feet. Dorsiflexing rotation of the feet is followed by a monosynaptic stretch reflex response in the gastrocnemius muscle, succeeded by a late compensatory tibialis anterior activation. Backward translation of the feet elicits only a compensatory polysynaptic EMG response in the gastrocnemius muscle, while an early gastrocnemius response is absent. The amplitude modulation of the gastrocnemius H-reflex has been investigated during the early part of the two modes of perturbation. Only during translational perturbation a progressive decrease in gastrocnemius H-reflex amplitude started within 5 ms after onset of displacement. The degree of the reduction in amplitude in the former perturbation was dependent on the displacement velocity. Only the contact forces (torques) differed between the two modes of perturbations within the first 10 ms after onset of perturbations. It is suggested that signals from pressure receptors within the body are responsible for the early change in H reflex amplitude during translational perturbations and it is concluded that the simplest spinal reflex is under very rapid and powerful moment-to-moment control by changes in peripheral feedback. In view of a strong reciprocal modulation of monosynaptic and polysynaptic reflex responses, the later purposive EMG responses may be determined by early changes in presynaptic inhibition of group I afferents. PMID- 1866088 TI - The severity of excitotoxic brain injury is dependent on brain temperature in immature rat. AB - The effect of brain temperature on the severity of excitotoxic brain injury was evaluated in perinatal rats. Postnatal day (PND) 7 rats received unilateral intrastriatal injections of 25 nmol N-methyl-D-aspartate (NMDA) and then were exposed for 2 h to one of six different ambient temperatures. Animals were sacrificed 5 days later and the severity of brain injury was assessed quantitatively by comparison of the weights of the injected and contralateral cerebral hemispheres. Injection of NMDA consistently produced extensive unilateral brain injury in rats maintained at normothermia (36 degrees C ambient temperature; 29 +/- 1.8% reduction in the weight of the injected hemisphere). In the range of ambient temperatures between 25 degrees C and 40 degrees C, there was a linear relationship between temperature and the severity of NMDA-induced injury (r2 = 0.95, P less than 0.001, linear regression). In a separate analysis, in PND 7 rats, a positive linear relationship between ambient temperature (28 degrees C and 40 degrees C) and brain temperature was observed (r2 = 0.96, P less than 0.001). These data suggest that the severity of excitotoxic brain injury is dependent upon brain temperature. PMID- 1866089 TI - A capstone experience in the baccalaureate curriculum. AB - Nurse educators focus on the competencies of graduates and the outcomes of undergraduate education. A capstone, the integrative end-of-program experience in the major, allows students to synthesize their learning with a focus toward their future practices and shows achievement of curriculum goals. The authors describe a capstone experience for the nursing major, proposing mechanisms for developing and evaluating a capstone in the baccalaureate nursing curriculum. PMID- 1866090 TI - Through the eyes of a nurse: a summer program for kids. AB - The author describes a summer program that is designed to stimulate an interest in nursing in grade school children. The 2-week calendar is described. PMID- 1866091 TI - Public health nursing partnership: agencies and academe. AB - The authors describe an approach to bridging the education-practice gap in nursing through a joint venture between a nursing center in a college of nursing and a public health department. The purposes of the cooperative efforts are defined and the services described. Administrative problems and solutions in such a venture are explored and evaluation methods explained. Finally, opportunities for expansion of the venture are considered. PMID- 1866092 TI - Ethical case analysis using a hospital bill. AB - When nursing ethics is integrated into the curriculum, it may be difficult to discern the best way to offer essential content to students. Faculty members who are charged with the responsibility of integrating ethics content will find the use of ethical case analysis helpful and effective. The author offers a unique application of ethical case analysis that incorporated the use of a patient bill to help students to learn about the complex issues of justice and the allocation of scarce critical care resources. PMID- 1866093 TI - Creatively teaching the interrelationships of a nursing model. AB - Nursing students find that the abstract description of nursing models is difficult to understand and apply. On the other hand, strategies that operationalize these concepts through concrete applications within everyday experiences help to promote the students' understanding. The author describes an exercise for teaching nursing students the central concepts of a nursing model. PMID- 1866094 TI - Reliability and validity of the productivity environmental preference survey (PEPS). AB - This study was conducted to establish the reliability and validity of the Dunn, Dunn, and Price Productivity Environmental Preferences Survey (PEPS) with baccalaureate nursing students and to identify differences between subpopulations (age, class level, sex, type of student (RN versus generic] and students at risk. The findings have implications for nurse educators who choose teaching-learning experiences for a diverse student population. PMID- 1866095 TI - Fundraising: developing and using the advisory board. AB - Fundraising is an essential yet undeveloped activity for administrators of schools of nursing. Advisory boards, longstanding adjuncts to schools of nursing, are an untapped resource for fundraising. Strategies to develop financial support are presented using knowledge, human behavior, and motivation. PMID- 1866096 TI - Secondary analysis: expanding survey research by faculty members. AB - Secondary analysis is a valid, efficient, and effective method of research that is under-used by nurse researchers. It can be used effectively by beginning and advanced researchers among the nursing faculty members to expand survey research, and thus increase their research productivity. The benefits of secondary analysis, particularly in survey research, are many, but the researcher must be cognizant of the risks as well so that their effect can be minimized. PMID- 1866097 TI - Helping students use research in the clinical setting. AB - This series of articles, Managing Your Academic Career, presents ways to intentionally improve your teaching. This first article explains the concept of becoming an intention teacher. Subsequent articles will deal with strategies that are useful in clinical teaching, such as preparing students to value and use research in practice, and providing feedback to students in the clinical setting. PMID- 1866098 TI - Self-concept among senior students in four types of nursing education programs. PMID- 1866099 TI - Teaching basic sciences to nursing students: the effects of an accelerated lecture schedule. PMID- 1866100 TI - ADN-MD partners. PMID- 1866101 TI - Comparison between exercise myocardial perfusion and wall motion using 201Tl and 191Irm simultaneously. AB - By exploiting the ultrashort half-life 191Irm as tracer for left ventricular first-pass angiocardiography and 201Tl as myocardial perfusion agent, direct comparison between myocardial perfusion and regional wall motion was obtained during the same exercise stress test in patients with non-significant coronary artery disease, in patients with recent myocardial infarction, and in patients six weeks after successful percutaneous transluminal coronary angioplasty (PTCA). A good agreement between regional myocardial perfusion and regional wall motion was observed in patients with non-significant coronary artery disease and in most patients with recent myocardial infarction. In contrast, discrepancies occurred at maximal exercise in patients studied six weeks after successful PTCA: only 38% of the patients with no evidence of restenosis and with a completely normal myocardial perfusion scintigraphy had a normal regional wall motion at maximal exercise stress. According to these results, a normal uptake of 201Tl six weeks after PTCA would mean that the circulation has been successfully reestablished but without predicting the functional capacities of the myocardial cells which remain altered at least six weeks after the revascularization procedure in about two-thirds of the patients. We conclude that 191Irm in combination with 201Tl offers the opportunity of performing myocardial perfusion and wall motion studies simultaneously both at rest and during exercise. PMID- 1866102 TI - Radiological protection guidance for radioactive patients--new data for therapeutic 131I. AB - Patients leaving hospital after 131I treatment for thyrotoxicosis face restrictions on their contact with other members of the public. These restrictions depend on the level of residual body radioactivity which for practical purposes can be taken to be almost entirely in the thyroid gland. This study provides an appropriate data base from which to draw advice to patients consistent with current radiological protection requirements in terms of the duration of these restrictions. Thyroidal retention of 131I was measured in 77 thyrotoxic patients over a period of 1-50 days after a first therapeutic administration of the radionuclide. Mean 131I activity in the gland (+/- S.D.) at 1 day was 56.1 +/- 11.1% of the administered dose activity and thereafter retention followed a single exponential decay pattern with a mean effective half life (+/- S.E.M.) of 6.35 +/- 0.14 days. In patients who required further 131I therapy, there was evidence that retention could be markedly reduced if there was virtual ablation of thyroid tissue. It is proposed that these retention data can be used to determine body radioactivity at any interval after the administration of 131I for treatment of thyrotoxicosis, thus obviating the need for serial measurements in every individual patient. PMID- 1866103 TI - The use of induction in the design of an expert system for thyroid function studies. AB - In this study, the role of induction in the design of an expert system for diagnosing thyroid disorders is evaluated. An expert system was first designed conventionally, based on interaction between a knowledge engineer and a thyroid specialist. This involved weighting three tests (T3, free T4 and TSH) according to the reliability of the test and the presence or otherwise of influencing factors. Compatibility was then tested with known ranges for the parameter values, and a diagnosis made of one of three possible outcomes (euthyroid; hypothyroid; hyperthyroid). Two expert systems were then induced using, firstly, a set of rules and, secondly, a sample set chosen from a database. These systems were then tested against the expert designed system. Both induced systems produced results which were superior to the expert designed system and, in addition, provided insight into the decision-making process. It is concluded that induction is very useful in the design of expert systems of this nature. PMID- 1866105 TI - Effects of extra-renal background subtraction and kidney depth correction in the measurement of GFR by gamma camera renography. AB - 99Tcm-DTPA gamma camera renography was performed in 83 patients with a wide range of renal function. An uptake index (UI) proportional to the single kidney glomerular filtration rate (GFR) was calculated from the renograms according to two different algorithms, one based on a blood background taken from a region of interest (ROI) over the heart (method I), and the other a modification of that procedure including an extra-renal background subtraction (method II). The extra renal background was defined by a ROI closely surrounding the kidney, making the separation between the extra-renal background and intra-renal blood background possible. Method II was further evaluated by comparing the results without and with correction for kidney depth (method III), the skin-kidney distance being measured by sonography. Calculated UI from the renograms was compared with measured 51Cr-EDTA plasma clearance as the reference method. Method I overestimated GFR at low kidney function. Addition of the extra-renal background subtraction (method II) eliminated that error and correction for kidney depth improved the accuracy (the standard error of the estimate was reduced from 18.2 min-1 to 12.3 min-1). It is concluded that the measurement of GFR by gamma camera renography is improved by these additional operations. PMID- 1866104 TI - Functional liver imaging with 99Tcm-galactosyl-neoglycoalbumin (NGA) in alcoholic liver cirrhosis and liver fibrosis. AB - Synthesis of 99Tcm-galactosyl-neoglycoalbumin (99Tcm-NGA), a recently described new radioligand with high specificity for hepatic binding protein (HBP), a galactose-residue specific receptor on hepatocytes, was carried out by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside to the primary amino groups of human serum albumin. NGA was purified by ultrafiltration and size exclusion high-pressure liquid chromatography (HPLC). Using a computer-based simulation program, time-activity data for the liver and precordium, blood radioactivity 2 min after i.v. injection of the radioligand, the association constant of 99Tcm-NGA-binding to HBP measured on human liver biopsies in vitro, and other patient-related parameters were put into a five-state non-linear model describing the pharmacokinetics of 99Tcm-NGA. By fitting the parameters of the model iteratively to the experimental data, an estimate of HBP concentration in the liver and of total liver blood flow was obtained. Using this model we studied 32 patients (53 +/- 11 years) with different clinical stages of alcoholic liver cirrhosis. Child B and Child C stage cirrhotic patients had a lower HBP concentration in the liver compared to control individuals (0.96 +/- 0.21 mumol l 1). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP concentration (0.27 +/- 0.15 mumol l-1) than Child A patients (0.66 +/- 0.21 mumol l-1; P less than 0.01) and Child B patients (0.53 +/- 0.18 mumol l-1; P less than 0.05). In four patients with biopsy-proven liver fibrosis (0.84 +/- 0.20 mumol l-1) no difference in receptor concentration from normal individuals was estimated. Changes in liver blood flow were not significant between the groups. A direct comparison of HBP concentration estimated in vivo by 99Tcm-NGA functional imaging and HBP concentration measured in vitro on a surgically removed liver biopsy specimen from the same patient with a normal liver and liver cirrhosis showed good matching of these two values. The results suggest that in vivo estimation of HBP concentration in the liver by 99Tcm-NGA functional imaging might be a suitable method for determining liver cell mass. PMID- 1866106 TI - Functional assessment of human gastrointestinal tract using 99Tcm-latex particles. AB - 99Tcm-latex particles (LP) is a newly developed radiopharmaceutical for the evaluation of the gastrointestinal (GI) tract. Following oral ingestion, it passes through the entire GI tract undissolved. The purpose of the present investigation was to introduce the clinical application of 99Tcm-LP. A group of 11 healthy volunteers was studied. Following a 12 h fast, the subjects were given 150 ml of water containing 37 MBq of 99Tcm-LP orally. Dynamic images up to 2 h were recorded to document temporal progression of radioactivity. Static images of the abdomen and whole body were taken at intervals. In normal subjects the tracer arrival times at the caecum and sigmoid colon were 3.2 +/- 0.9 and 11.2 +/- 3.2 h, respectively. The average t1/2 value for gastric emptying, 50% colonic filling and small bowel transit time were found to be 21.6 +/- 5.6, 233 +/- 72 and 211 +/ 66.4 min, respectively. In conclusion, 99Tcm-LP has the potential of providing functional information of the GI tract. PMID- 1866107 TI - Validation to eliminate vascular activity on 99Tcm-HMPAO brain SPECT for regional cerebral blood flow (rCBF) determination. AB - Since more than 15% of the injected dose of 99Tcm-HMPAO 10 min after injection labels plasma or red blood cells (RBC), the elimination of vascular activity from actual brain activity is mandatory to evaluate accurately regional cerebral blood flow (rCBF) with 99Tcm-HMPAO brain SPECT. The late image (4 h post-injection) will show a reduced vascular activity of approximately 30% compared to the initial image (30 min post-injection), due principally to a plasma fraction reduction of 54%, and an insignificant reduction of activity in the RBC fraction. The circulating RBC count can then be normalized for both the injected dose and total blood volume, because the entrapment mechanism of 99Tcm-HMPAO with RBC is the same as that with brain retention. After elimination of the vascular contribution using the RBC activity the mean counts in the 14 middle cerebral artery areas from seven cases on 99Tcm-HMPAO SPECT showed a good correlation (r = 0.85) with the initial slope index of 133Xe cerebrography. It was concluded that the elimination of the vascular activity on 99Tcm-HMPAO brain SPECT is needed to quantify rCBF accurately. PMID- 1866108 TI - Quantitative 99Tcm-HMPAO white blood cells and 67Ga scanning in rheumatoid arthritis. AB - This investigation assessed 99Tcm-HMPAO white blood cell (Tc-WBC) and 67Ga knee uptake indices before and after 90Y treatment in patients with intractable rheumatoid arthritis (RA) and correlated the uptake indices with the clinical score. Sixteen knee joints with RA were treated with intra-articular injection of 185 MBq of 90Y-silicate colloid (Amersham) flushed with 50 mg of hydrocortisone. Clinical score, quantitative 67Ga and Tc-WBC knee uptake indices were obtained before and three weeks after treatment. Our results showed that 9/16 (56%) had a good response and 7/16 (44%) had a poor response to 90Y injection. There was poor correlation between clinical improvement and changes in 67Ga and Tc-WBC knee uptake indices (r = 0.46 and 0.14, respectively). The correlation coefficient between changes in 67Ga and Tc-WBC knee uptake indices was 0.29. PMID- 1866109 TI - Letter from America. PMID- 1866110 TI - The fatty meal in 99Tcm-MIBI myocardial imaging. PMID- 1866111 TI - Robotics. Safety developments and applications in the 1990s. PMID- 1866112 TI - Hazardous-waste operation training: the University of Wisconsin approach. PMID- 1866113 TI - Safety engineers have obligation to control hazards through design. PMID- 1866114 TI - Engineers, safety professionals work on total ergonomic quality. PMID- 1866115 TI - Hazardous-waste storage program sends positive message to workers. PMID- 1866116 TI - Chemical process safety needs effort from industry, government and public. PMID- 1866117 TI - Standards, codes, regulations help keep indoor air quality acceptable. PMID- 1866118 TI - Electronic claims filing not without cost. PMID- 1866119 TI - Health care's future. PMID- 1866120 TI - The risks of quality assurance. PMID- 1866121 TI - Cincinnati lags in AIDS cases. PMID- 1866122 TI - AIDS and your office staff. PMID- 1866123 TI - Developmental changes in the ferret ileum during the postnatal period. AB - The development of the ferret ileum was studied in order to determine the pattern of morphological maturation during the postnatal period. In the newborn, intestinal villi were short, and lined by simple columnar enterocytes with striated borders and small vacuoles. At one week old, the equivalent cell had large vacuoles that were shown on TEM to be related to a tubulovesicular system in the apical region of the cytoplasm. At two and three weeks old, the epithelial cells at the same site showed a more extensive tubulovesicular system, and vacuoles occupied major areas of both the supra- and subnuclear cytoplasm. At six weeks old (weaning), although the enterocytes contained a few small intracellular vesicles, they appeared histologically more mature than in previous stages. At nine weeks and in the adult, the villi were longer and the enterocytes no longer contained vacuoles. In TEM, the epithelial cells had long microvilli, and the apical tubulovesicular system and vacuoles had completely disappeared from the cytoplasm. PMID- 1866124 TI - Synaptic connections of extrinsic nerve fibers in the myenteric plexus of the rat duodenum. AB - In the present study the degeneration of extrinsic nerve fibers was first investigated in the duodenal myenteric plexus after their transection, and subsequently synaptic connections of the extrinsic nerve fibers were observed with their degenerative changes to examine the relationship of the extrinsic nerve fibers with the neuronal circuits in the myenteric plexus. Adult rats were anesthetized with pentobarbital, and the extrinsic nerve fibers running with the coeliac and superior mesenteric arteries were cut at about 2 mm distance from the coeliac ganglia to duodenum. Their duodena were fixed at 6 and 12 hours, and 1, 2, 4, 7 and 11 days after the extrinsic denervation, and their myenteric plexuses were observed with the electron microscope. Then, montages on 22 fields of the myenteric plexuses of 7 days after the denervation were made, and the number of all synapses and degenerated synapses in them was counted in each montage. 1. The degenerated changes of the extrinsic nerve fibers Three types of the degenerated axons were found in stages ranging from 12 hours to 11 days after the extrinsic denervation as follows: 1) Type I appeared mainly at 1 and 2 days. The electron density in the axoplasm decreased, and the synaptic vesicles accumulated in the central area of the axoplasm. 2) Type II appeared, also, at 1 and 2 days. The electron dense material occupied the axoplasm or the myelin-like structure appeared in the slightly swollen axons. 3) Type III appeared in stages from 1 to 11 days. Electron dense bodies appeared in the axoplasm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866125 TI - Histological examination of chick embryos with bilateral microphthalmus with reference to laterality in the visual apparatuses. AB - The histological abnormalities of chick embryos with bilateral microphthalmus were examined in serial paraffin sections with special reference to laterality in the visual apparatuses, including the cornea, lens, neural retina and pigment epithelium. There was marked laterality in the above structures; some eyeballs had individual, if incomplete, sublayers of the cornea and the neural retina, and others not. The sublayers of the neural retina were occasionally observed even in eyeballs at the stage of optic vesicle formation, in contrast to the previous notion that the pigment epithelium induces the maturation of the primordial neural retina after optic vesicle differentiation into the optic cup. There was also a case where developmental differences between the right and left eyeballs were absent except in the lens. These findings suggest that chick embryos with bilateral microphthalmus exhibit a more complex histological profile or diversity than previously considered, possibly as a result of the differential actions of various mutagens and endogenous trophic factors on the developing visual system. PMID- 1866126 TI - Immunoelectron microscopical demonstration of egg-yolk plasma precursor vitellogenin in the hepatocyte of oestradiol-treated cockerels. AB - Vitellogenin has been localized at the electron microscopical level in the liver of the cockerel using a colloidal gold technique. White leghorn cockerels were treated with 17 beta-oestradiol to induce vitellogenesis. Pieces of liver were removed from control and experimental birds on the 4th and 8th days following hormone treatment, and embedded in Lowicryl K4M. Vitellogenin was isolated from the plasma of oestradiol-treated cockerels, and the antibody to it elicited in rabbits and made vitellogenin-specific by affinity chromatography on lipovitellin Sepharose columns. At the light microscopical level, the intensity of immunohistochemical staining was considerably above background levels in oestradiol-treated cockerels. At the electron microscopical level, gold particles indicating antigenic sites of vitellogenin were largely confined to the rough endoplasmic reticulum, Golgi apparatus, immature and lysosomes and phagosomes within hepatocytes and sinusoidal cells respectively. These observations strongly suggest that the intracellular pathway of vitellogenin secretion in chicken hepatocytes under the experimental conditions studied involves external stimuli and secretory vacuoles. The labelling of lysosomes may reflect catabolic turnover (crinophagy). PMID- 1866127 TI - Atrioventricular and ventriculo-atrial branches of the human coronary arteries supplying the walls of heterolateral cardiac chambers. AB - In 20% of 40 human hearts, AV and VA branches of the coronary arteries supplied the wall of cardiac chambers on the opposite side of the heart. VA branches were more frequent than AV branches and both were observed at the level of the crux cordis (in the diaphragmatic aspect of the heart). PMID- 1866128 TI - A tongue-like projection of the left lobe in human liver, accompanied with lienorenal venous shunt and intrahepatic arterial anastomosis. AB - The characteristic features of a tongue-like projection of the left lobe of the liver in a female adult, accompanied with a large lienorenal venous shunt and an intrahepatic anastomosis of the hepatic arteries, are described. By dissecting the liver parenchyma, this projection is supplied by a set of the lateral segmental branches of the portal vein, hepatic artery and hepatic ducts and by the branch of the left hepatic vein. The boundary between the abnormal and the proper left lobes can not be confirmed accurately, because the tongue-like projection is overlapped with the paraumbilical lobe on the visceral surface. However, the position is estimated a transverse line superior to the attachment to the proper left lobe. The anomaly is derived from a medial and inferior portion of the left lobe of the liver and may be regarded as a left half of the central lobe in the ape etiologically. No evidences to justify the co-existence of the tongue-like projection with the lienorenal shunt are confirmed. PMID- 1866129 TI - Effect of denervation on the neuron-specific enolase immunoreactivity of Merkel cells in the taste organs of the frog. AB - The changes in neuron-specific enolase (NSE) immunoreactivity of Merkel cells in the frog taste organ were investigated up to 5 months after resection of the glossopharyngeal nerve. Even at 5 months after denervation, the denervated Merkel cells exhibited an immunoreaction with NSE antiserum. PMID- 1866130 TI - A macroscopic study of the internal thoracic artery of the rat. AB - The internal thoracic artery (ATI) of rats was macroscopically studied. In this study, the overall features of the artery were virtually elucidated in entirety. The artery was found to arise from the subclavian artery in the thoracic cavity and to immediately break up into the following branches: (1) the pericardiacophrenic artery, (2) the superior epigastric artery, (3) the thymic branch, (4) the comitans branch to the brachiocephalic veins, and finally (5) the bronchoesophageal trunk. As is well known, rats are devoid of the superior caval veins, retaining instead a pair of brachiocephalic veins into adulthood; this is a greatly beneficial condition as it enables us to consider the essential relationships of the ATI to relevant structures which are thought to be directly involved in the development of the ATI. In fact, the rat ATI revealed topographically a remarkable intimacy with the phrenic nerve, the brachiocephalic and inferior caval veins, the heart and lungs and also with the diaphragm; in their development all are in close relationship with the pleuropericardial fold. This fact leads us to the opinion that, for a better understanding of the morphological meanings of the ATI, an understanding of the relationship of this artery to the pleuropericardial fold seems to be a prerequisite. PMID- 1866131 TI - Glaucoma laser trial. PMID- 1866132 TI - Pseudo-loss of fixation. PMID- 1866133 TI - Retrograde retinal degeneration. PMID- 1866134 TI - Corticosteroids: an unresolved debate. PMID- 1866135 TI - Use of corticosteroids in combination with antimicrobial drugs in the treatment of infectious corneal disease. AB - The use of corticosteroids in the management of infectious eye disease is controversial. In this study, the authors attempt to analyze the goals and risks of the use of corticosteroids in the treatment of various forms of infectious keratitis with reference to generally recognized principles for the treatment of infectious diseases. Existing clinical and research data are reviewed in this context to make appropriate recommendations for the use of corticosteroids in the treatment of bacterial, fungal, and acanthamoeba keratitis. The authors conclude that corticosteroids are definitely contraindicated in the treatment of fungal keratitis, and relatively contraindicated in the treatment of Acanthamoeba keratitis. Topical corticosteroid therapy may have a role in the treatment of bacterial keratitis if appropriate guidelines are followed. PMID- 1866136 TI - Effect of contact lens preservatives on Acanthamoeba. AB - Single preservatives used in contact lens solutions were evaluated for their effectiveness in killing Acanthamoeba castellanii and Acanthamoeba polyphaga trophozoites and cysts. Preservatives were tested against amoebae at intervals varying from 30 minutes to 24 hours. The preservatives were tested with axenically and nonaxenically grown organisms. Chlorhexidine (0.001% and 0.005%), polyaminopropyl biguanide (0.0015%), benzalkonium chloride (0.001% and 0.004%), and hydrogen peroxide (3%) were very effective preservatives. Lower concentrations of these same preservatives were less effective. Thimerosal (0.001% and 0.004%), sorbic acid (0.1%), potassium sorbate (0.13%), EDTA (0.1%), polyaminopropyl biguanide (0.00005%), and polyquaternium-1 (0.001%) were not effective as tested. However, thimerosal 0.004% when combined in solution with EDTA was effective. Preservatives were more effective when tested against axenically prepared organisms than when tested against co-cultured organisms. PMID- 1866137 TI - Remission and recurrence after withdrawal of therapy for ocular cicatricial pemphigoid. AB - Ocular cicatricial pemphigoid (OCP) is a chronic, progressive, autoimmune disease that scars mucus membranes and may lead to blindness. The authors studied the long-term effects of OCP in 104 consecutive patients (average follow-up, 4 years) to determine whether complete remission could be achieved after a course of treatment with immunosuppressive drugs. Prolonged periods of remission while not undergoing therapy were maintained in approximately one third of patients with OCP. Follow-up must be continued for life, as relapse occurred in 22% of those who were in remission and not undergoing therapy. Those who relapsed regained disease control readily upon reinstitution of therapy and did not deteriorate to more advanced cicatrization. Sex, age, initial degree of inflammation, and the incidence of extraocular involvement did not have a prognostic significance on outcome. Mechanisms that underlie the differing responses to therapy are not yet known. PMID- 1866138 TI - Antimicrobial efficacy and corneal endothelial toxicity of DexSol corneal storage medium supplemented with vancomycin. AB - Despite the presence of gentamicin in corneal storage medium, postoperative endophthalmitis may result from the transmission of bacteria via contaminated corneal tissue. The authors evaluated the antimicrobial activity and endothelial toxicity of vancomycin (10 micrograms/ml) in combination with gentamicin (100 micrograms/ml) in DexSol corneal storage medium. When tested against a panel of common ocular pathogens, vancomycin combined with gentamicin proved more effective than gentamicin alone for inhibiting the growth of Streptococcus pneumoniae at 4 degrees C after 1- and 5-day incubation periods. Ultrastructural and morphometric analyses of paired human corneas stored for 5 days in either DexSol supplemented with vancomycin combined with gentamicin or DexSol with gentamicin alone did not show a significant difference in endothelial toxicity between the two groups. These results suggest that vancomycin combined with gentamicin has superior antimicrobial effect and similar corneal toxicity when compared with media supplemented with gentamicin alone. PMID- 1866139 TI - Dissolution of intraocular fibrinous exudate by streptokinase. AB - In a prospective, open, pilot study, the authors evaluated the effects of intraocular injection of streptokinase on intraocular fibrin. The study was composed of nine patients in whom fibrinous exudate developed after pars plana vitrectomy. There were seven male and two female patients with a mean age of 44 years (range, 27 to 65 years). Fibrinous exudates were seen 1 to 22 days after surgery with obstruction of the view of the posterior segment. Each patient received a single intraocular injection of 1000 IU of purified streptokinase. Four hours after the streptokinase injection, complete dissolution of the fibrin was noted in each patient. There were no clinically detectable adverse effects from the intraocular administration of streptokinase. Streptokinase may be considered in the dissolution of intractable intraocular fibrinous exudates after vitrectomy. PMID- 1866140 TI - Implantation of Kelman-style, open-loop anterior chamber lenses during keratoplasty for aphakic and pseudophakic bullous keratopathy. A comparison with iris-sutured posterior chamber lenses. AB - The clinical and specular microscopic results of 40 cases (39 patients) of penetrating keratoplasty during which a Kelman-style anterior chamber intraocular lens was implanted were reviewed retrospectively. Thirty-one pseudophakic eyes received an intraocular lens exchange and nine aphakic eyes received a secondary intraocular lens. Postoperative follow-up averaged 24.5 months (range, 3 to 51 months). At 1, 2, and 3 years after keratoplasty, 39.3%, 63.2%, and 63.6% of eyes, respectively, had visual acuities of 20/40 or better. Ninety-five percent of the grafts remained clear. Causes of poor postoperative visual acuity included cystoid macular edema (32.5%), new glaucoma (22.5%), and age-related macular degeneration (10.0%). Other causes were endothelial rejection leading to graft failure, corneal ulceration, and retinal detachment. Corneal endothelial cell loss by specular microscopy was 11.5% at 1 years, 21.3% at 2 years, and 25.0% at 3 years. These results were compared with cell loss associated with iris-sutured posterior chamber lenses in penetrating keratoplasty. Visual outcomes and complication rates were similar between these two methods; however, the endothelial attrition at 1 and 2 years for the sutured posterior chamber lens was greater than that of the Kelman anterior chamber lens. PMID- 1866141 TI - Visual and refractive results of multifocal intraocular lenses. AB - One hundred forty-nine selected patients with bilateral multifocal intraocular lenses (IOLs) were evaluated and compared retrospectively with 131 patients with bilateral monofocal IOLs. Seventy-eight percent of multifocal cases and 74.8% of monofocal cases had uncorrected visual acuity of 20/40 or better. Fifty-four percent of multifocal cases had near uncorrected visions of J1 to J3. Eighteen percent had best-corrected near vision of J4 or worse. Sixty-three percent of multifocal cases versus 4% of monofocal cases needed no spectacle correction. Multifocal cases reported significantly more visual side effects (flare, glare, and halos). The 10% of cases with poor satisfaction (rating vision as fair-to poor) had significantly (P = 0.03) more postoperative astigmatism (1.1 prism diopters [D] versus 0.74 D) compared with satisfied (good-to-excellent) cases. Patients who were dissatisfied reported more need for corrective lenses but not more side effects. A greater decrease in contrast sensitivity at low contrast levels was detected among multifocal cases. Both groups had similar contrast sensitivity at 96% and 50% contrast, but at 11% contrast, multifocal cases averaged a loss of 3.45 Snellen lines (to 20/48.2) compared with 2.65 lines (to 20/36) for monofocal cases. PMID- 1866142 TI - Management of dislocated posterior chamber intraocular lenses. AB - Management options for posteriorly dislocated posterior chamber intraocular lenses include observation, removal, exchange, and repositioning. Many microsurgical techniques have been developed for repositioning posterior chamber implants. These include repositioning into the ciliary sulcus without suturing if adequate posterior capsule support remains, iris fixation suturing techniques, and scleral fixation suturing techniques. The indications, timing, and techniques for intervention are reviewed in a series of 32 cases with posteriorly dislocated posterior chamber implants. A final visual acuity of 20/40 or better was achieved in 15 (79%) of 19 IOL repositioned cases, in 6 (75%) of 8 IOL exchanged cases, and in 1 (33%) of 3 IOL removed cases. In two patients observed without surgery, final visual acuity was 20/25 and 20/300, respectively. PMID- 1866143 TI - National outcomes of cataract extraction. I. Retinal detachment after inpatient surgery. AB - Rehospitalization for retinal detachment (RD) was studied in 338,141 Medicare beneficiaries older than 65 years of age who were undergoing inpatient cataract extraction in 1984. Extracapsular cataract extraction (ECCE) was performed in 60% of patients, intracapsular cataract extraction (ICCE) in 31%, and phacoemulsification in 9%. The risk of rehospitalization for RD within 4 years of ICCE was 1.55% over 1.5 times the risk associated with ECCE (0.9%). The risk of RD after phacoemulsification was 1.17%. Cataract surgery accompanied by anterior vitrectomy was associated with a 5.0%, likelihood of RD at 4 years, which is 4.5 times greater than that for cataract surgery alone (1.12%). White patients were 1.7 times more likely to be rehospitalized for RD than were black patients (1.15% versus 0.67%; P less than 0.001). In both races, younger patients were more likely to be rehospitalized for RD than were older patients (P less than 0.001). While the increased rate of RD after ICCE versus ECCE confirms previously held clinical beliefs, the increase in the risk following phacoemulsification (P less than 0.0001) has not been reported previously. PMID- 1866144 TI - Visual results after early surgical treatment of unilateral congenital cataracts. AB - The authors reviewed the records of 25 consecutive patients who had been operated on for unilateral congenital cataracts at 1 year of age or younger and who had been followed for a period of 5 years or longer. Excluded were patients who demonstrated retinal and optic nerve anomalies. Five eyes achieved 20/40 or better Snellen visual acuity, 5 eyes achieved 20/50 to 20/100 visual acuity, and 15 eyes had 20/200 or less visual acuity. All patients with visual acuity of 20/40 or better had cataract surgery performed before 17 weeks of age, the critical period, and surgery was scattered within this time frame. For surgery performed between 17 weeks and 1 year of age, the best achieved visual acuity in children with surgically significant unilateral congenital cataracts was between 20/50 and 20/100. There was no correlation between the age at the time of surgery and the attainment of these visual levels in this patient subset. PMID- 1866145 TI - Incomitant dissociated vertical deviation and superior oblique overaction. AB - When superior oblique overaction coexists with dissociated vertical deviation, it may produce a pattern of disparity in the amount of dissociated vertical deviation in different horizontal gaze fields, which the authors have termed incomitance. Seven patients with the constellation of esotropia, bilateral superior oblique overaction, "A"-pattern, and incomitant dissociated vertical deviation are presented. In each case, a distinctive incomitant pattern of dissociated vertical deviation was noted in which dissociated vertical deviation was least in adduction, moderate in primary position, and greatest in abduction. Four patients underwent asymmetric superior rectus recessions and partial tenotomy of the superior oblique tendons at their insertions as the initial treatment for their incomitant dissociated vertical deviation. Recognition of such a pattern of incomitant dissociated vertical deviation is important in choosing appropriate surgical management. PMID- 1866146 TI - Hemangiopericytoma of the lacrimal sac. AB - Hemangiopericytomas of the orbit are rare tumors with low malignancy potential. To the authors' knowledge, only three previous cases of these tumors occurring in the lacrimal sac have been reported. The authors report a fourth case. Follow-up was obtained on the first reported case, and the patient in that case had a recurrence after 15 years. These tumors should be totally excised and followed for long periods of time. PMID- 1866147 TI - Tissue eosinophilia and eosinophil degranulation in orbital pseudotumor. AB - To investigate the participation of the eosinophil in orbital pseudotumor, the authors studied surgical biopsy specimens from nine patients with pseudotumor. Surgical biopsy specimens of orbital tissue from four patients with Graves' ophthalmopathy and autopsy specimens of orbital tissue from six patients without orbital diseases served as controls. Eosinophil infiltration and degranulation were assessed by immunofluorescence staining of formalin-fixed, paraffin-embedded tissues for the cytotoxic eosinophil granule major basic protein. Eosinophil infiltration and extracellular major basic protein deposition were evident in all orbital pseudotumor specimens. In contrast, no eosinophil infiltration or extracellular major basic protein deposition was present in any of the ten control specimens. These findings indicate that eosinophil degranulation is found in orbital pseudotumor, and they also identify yet another clinical entity where eosinophil infiltration and degranulation are associated with fibrosis. PMID- 1866148 TI - Biofilm and scleral buckle-associated infections. A mechanism for persistence. AB - Scleral buckle infections tend to be persistent as well as resistant to antimicrobial treatment. Often, scleral buckle infections require removal of the buckling elements for resolution. To determine if bacteria are able to persist on scleral buckles by elaborating a glycocalyx matrix or biofilm that offers protection against host defenses and antimicrobial treatment, the authors cultured 28 scleral buckle elements removed for infection and extrusion. Bacteria were isolated from 18 elements (64%). The most frequently isolated bacteria were Staphylococcus epidermidis and other coagulase-negative staphylococci (8), Staphylococcus aureus (3), corynebacteria (3), Mycobacterium chelonei (3), and Proteus mirabilis (3). Eleven (65%) of 17 buckles evaluated with scanning electron microscopy demonstrated the presence of bacteria encased in biofilm. Biofilm was demonstrated on the surfaces and ends of solid silicon elements. In the silicon sponges, biofilm also extended into the matrix of the sponges. The authors believe that bacterial production of biofilm offers an explanation for the persistence of scleral buckle infections and their ability to withstand antimicrobial treatment. PMID- 1866149 TI - Triple agent immunosuppression in serpiginous choroiditis. AB - Serpiginous choroidopathy is a progressive choroidal inflammatory disorder that typically has a variable saltatory course. Response to steroids is uncertain. By using azathioprine, cyclosporine, and prednisone in combination, the authors have observed rapid remission of active disease in five patients. Remissions have been maintained for periods up to 18 months. Because of the synergistic effects of this combination, doses could rapidly be reduced to maintenance levels without reactivation. Disease in two patients recurred immediately after discontinuation of low-dose therapy but was arrested when therapy resumed. Triple agent immunosuppressive therapy is well tolerated and appears to be effective. PMID- 1866150 TI - Histopathology of incipient fundus flavimaculatus. AB - A 9-year-old boy was diagnosed with fundus flavimaculatus in his left eye. The boy's fellow eye was enucleated at 16 months of age for retinoblastoma. The authors reviewed the material submitted for histopathologic examination and found that the retinal pigment epithelial cells demonstrated increased autofluorescence and increased reactivity to periodic acid-Schiff staining. Many cells had their melanin granules displaced toward the cell apex. The retinal pigment epithelial changes are consistent with previous histopathologic findings in fundus flavimaculatus and imply that the structural changes are seen in early life. PMID- 1866151 TI - Delayed rod dark adaptation in patients with Stargardt's disease. AB - Twelve patients with Stargardt's dystrophy were each found to have a prolongation in rod dark adaptation. All had a normal rate of recovery during the early portion of rod dark adaptation but a selective prolongation of the later segment of rod recovery. This observation was apparent in patients with limited fundus flecks and those with extensive fundus flecks, whether or not a dark choroid was observed and independent of the presence or absence of an atrophic-appearing macular lesion. A defect within retinal pigment epithelial cells of an enzyme or intracellular transport mechanism involved in the visual pigment regeneration cycle could account for these findings. PMID- 1866152 TI - Choroidal detachment associated with malignant choroidal tumors. AB - The association of choroidal detachment with malignant choroidal tumors is not well recognized. The authors' experience with six cases suggests that choroidal detachment may be associated with both metastatic tumors and choroidal melanoma. In two of these cases, the choroidal or retinal detachment was so massive that echography was necessary to detect the underlying tumor. Three patients presented with painful visual loss, and three patients presented with painless visual loss or a visual field defect. In one patient, the correct diagnosis and appropriate treatment of the choroidal metastasis with external radiation relieved the patient's pain and improved visual acuity from 1/200 to 20/35. Metastatic and primary uveal malignant tumors should be added to the list of causes of choroidal detachment and can be excluded only after thorough clinical, and often echographic, examination. PMID- 1866153 TI - Partial lamellar sclerouvectomy for ciliary body and choroidal tumors. AB - The authors reviewed the postoperative course, visual results, histopathologic findings, and mortality data on 95 consecutive patients with tumors of the ciliary body and/or choroid who were managed by a partial lamellar sclerouvectomy. This surgical procedure is designed to remove the uveal tumor and leave intact the outer sclera and sensory retina. In this group of 95 patients, vitreous hemorrhage occurred in 79 (83%) cases, intraretinal or subretinal hemorrhage in 33 (35%), retinal detachment in 26 (28%), and cataract in 32 (34%). Most of the vitreous and retinal hemorrhages resolved spontaneously, sometimes leaving subretinal or preretinal fibrosis. A number of the postoperative retinal detachments resolved spontaneously, but retinal detachment surgery was necessary in 16 patients (17%), mostly in the earlier years of the survey. Most of the cataracts were mild and did not require surgery. The eventual postoperative visual acuity was equal to or better than the preoperative visual acuity in 23 cases (24%) over a mean follow-up period of 5 years. Enucleation was eventually necessary in 15 cases (16%), usually because of residual or recurrent tumor. Histopathologic diagnosis was uveal melanoma in 81 cases (85%) and other tumors in 14 cases (15%). There were no orbital recurrences, but distant metastases developed in five patients (5%), all of whom had undergone enucleation for recurrence of the intraocular melanoma. Although the surgical technique is difficult, partial lamellar sclerouvectomy appears to be a reasonable therapeutic option in selected cases of posterior uveal tumors. PMID- 1866155 TI - Retinal capillary blood flow measurement with a scanning laser ophthalmoscope. Preliminary results. AB - The scanning laser technique in combination with digital image analysis allows direct objective measurement of flow velocities in perimacular capillaries. In addition, the complete macular network of capillaries can be observed. By means of digital frame-to-frame picture analysis of digital recordings, blood flow velocities and morphologic data have been measured. The mean flow velocity in perimacular capillaries observed with the scanning laser ophthalmoscope in healthy subjects (n = 21) amounted to 3.28 +/- 0.45 mm/second. In patients (n = 13) with diabetes mellitus (no or background retinopathy), the mean flow velocity was significantly reduced (2.89 +/- 0.57 mm/seconds) compared with healthy subjects. Morphologic data of the perifoveal capillary bed showed a significant reduction of capillaries in patients with diabetes mellitus when compared with healthy subjects. PMID- 1866154 TI - Impact of local tumor relapse on patient survival after cobalt 60 plaque radiotherapy. AB - The authors investigated the impact of local intraocular tumor relapse on survival in a matched-group comparison study of patients with primary choroidal or ciliary body melanoma managed with cobalt 60 plaque radiotherapy. Sixty-two patients with local relapse were matched with an equal number of relapse-free patients in terms of known clinical prognostic factors for both melanoma-specific mortality (largest linear tumor dimension, location of anterior tumor margin, age) and local tumor relapse (location of posterior tumor margin). The follow-up of every relapse-free patient equaled or exceeded the interval to relapse for each matched patient with local relapse. The estimated 5-year survival (Kaplan Meier) in the relapse-free patients was 87% (standard error = 4%), while that in the local relapse group was 58% (standard error = 6%). This difference is statistically significant (P less than 0.0001, log rank test). These results support the hypothesis that local tumor relapse after cobalt 60 plaque radiotherapy is an important post-treatment clinical indicator of the tumor's greater malignant potential and the patient's increased risk of melanoma-specific mortality. PMID- 1866156 TI - [Plasma prostacyclin and thromboxane concentration in healthy children and in offspring of parents suffering from myocardial infarct]. AB - 6-keto-prostaglandin F1a and thromboxane B2 were determined by radioimmunoassay in 135 healthy children, as a control group, and in 125 offsprings of parents suffering from premature coronary artery disease. Plasma prostacyclin concentration had decreased in children with a positive family history of coronary artery disease. It was demonstrated a strong reduction of thromboxane level in boys from age 11 in endangered group while the thromboxane/prostacyclin ratio did not differ from the control. It was supposed that in adolescent sons of parents who have had an acute myocardial infarction before the age of 45, a compensatory mechanism exists to protect them from disturbances in regulation of the balance between prostacyclin and thromboxane. PMID- 1866157 TI - [Effect of somatostatin analogue on experimental pancreatic lesions and their sequelae]. AB - The authors examined the effect of long acting somatostatin analogue (Sandostatin, Sandoz) on acute experimental pancreatitis and on the subsequent regeneration. Acute injury to the pancreas was produced by an intraductal intervention (ligature of the bile duct and intraductal injection of taurocholic acid) and by a metabolic route (supramaximal dose of caerulein by repeated subcutaneous injections). The effect of the drug on the acute injury was examined at 6 and 24 hours following the intervention and the effect on regeneration was examined on day 3 and 5 in all cases by determination of plasma enzyme levels and examination of the pancreatic tissue. Long acting somatostatin analogue did not prove to be effective in the serious acute pancreatitis produced by the intraductal intervention. However, in the acute phase of the caerulein induced pancreatitis, it had a beneficial effect as seen by it's ability to moderate the serum enzyme levels. During the examination of pancreatic regeneration was found that in caerulein induced pancreatitis the weight of the pancreas decreases due to atrophy and that this was not affected by long acting somatostatin analogue. As a matter of fact, the somatostatin counteracted the caerulein induced DNA increase, and therefore acted against the reactive hyperplasia. Therefore, the favorable effect of long acting somatostatin analogue is witnessed only in the caerulein induced acute injury but it does not accelerate the rate of pancreatic regeneration following injury. Due to this fact, protracted administration of this agent can not be rationalized. PMID- 1866158 TI - [Split hand/foot abnormalities: classification, pathogenesis, epidemiology]. AB - Authors report on the genetic epidemiologic investigation of one of the sentinel anomalies made on purpose to define the birth prevalence of the different types of it, to calculate the mutation rate of autosomal dominant forms as well as to recognize the clinical features of Hungarian cases. 58% of all cases registered in the Hungarian Congenital Abnormality Registry in 1975-1984 proved to be atypical. The birth prevalence of autosomal dominant forms was 1.33/100.000 total birth. 71% of dominant forms was sporadic since 29% was familial. Thus the mutation rate was estimated 4.7 x 10(-6) +/- 1.22 x 10(-6). PMID- 1866159 TI - [Experience with chorionic villi sampling]. AB - The authors discuss their experiences from 412 chorion villus samplings, (CVS), which they have done under four and a half years since 1985. They used eight types of instruments in performing their examinations and each instrument proved to be satisfactory in the gaining of chorion villus samples, suitable for further tests. They also discuss the bacteria found most frequently in the vagina on the basis of the examination and culturing of both vaginal and cervical fluid done prior to 151 CVS examinations and the effective method with which ascending infection can be prevented. They discuss a distributional pattern of their results based on the different indications for the CVS examinations, and the outcome of each of the pregnancies after CVS. In 377 cases they did direct karyotyping, in 30 cases DNA examination and in five cases enzyme determination also occurred. PMID- 1866160 TI - [When is surgical correction of the terminal ileum during appendectomy indicated?]. AB - During 1416 appendectomy operations we examined the ileum and found 42 cases of terminal ileum infraction (ileum terminale duplex) caused by the cicatrisation of the mesenterium. Nine of the forty-two had characteristic symptoms of terminal ileum infraction syndrome (stomachodynia and pain in the right lower part of the abdomen 4 or 5 hours after meals, distensions). Deliberation was performed in this cases at the time of the appendectomy operations. Following the operations they had no symptoms. When the infraction is severe or the patient has typical complaints of terminal ileum infraction syndrome necessitates the deliberation of the terminal ileum in our opinion. PMID- 1866161 TI - [Typhlitis as a complication of acute leukemia]. AB - The authors describe the clinical history of two adult patients with acute myeloid leukemia, who had severe neutropenia and thrombocytopenia. After chemotherapy in both patients had developed typhlitis with fatal outcome caused by sepsis. They discuss the etiopathogenesis and clinical features of necrotizing typhlitis as a complication of treated acute leukemia and point out the difficulty of the differential diagnosis and management. PMID- 1866162 TI - [The importance of Paracelsus (1493-1541) in the history of medicine]. PMID- 1866163 TI - [Judging the severity of regurgitation in acquired heart defects using color coded Doppler echocardiography]. AB - In the study, 139 valvular regurgitations of 120 patients (55 mitral and 84 aortic regurgitations) were investigated and compared by means of colour flow mapping and heart catheterization. During the echocardiographic examination, the length and width of the regurgitant jets were measured and the jet area was planimetered besides the subjective grades. The above parameters were correlated with the angiographic grades. Good agreement was found between the results of the two methods. As concerns the different parameters of the regurgitant jets in mitral regurgitation, the most severe (grade IV) category was easily distinguished from the others, while in aortic regurgitation all four categories were differentiated by colour flow mapping. These measurements indicated that colour-coded Doppler echocardiography is a suitable tool for detection of the severity of valvular regurgitations in a noninvasive way. PMID- 1866165 TI - [Diagnostic findings and decision making in the establishing of diagnosis]. AB - Instead of collecting data by far-reaching and unlimited investigations it is recommended to restrict our activity to rationalized and by thought selected examinations. To well appreciate the value of data we must well know the sensitivity and specificity of different examinations. These principles are in practice often not realized and that causes easily diagnostical polypragmasy, even false diagnosis. The author illustrates the mentioned method by examples taken from the process of raising diagnosis in different respiratory diseases (localized infiltrations of the lung, nodular pulmonary disseminations, pulmonary embolism, chronic persistent cough). PMID- 1866164 TI - [Experience with cytostatic therapy of stomach cancer]. AB - The authors have been working on the cytostatic treatment of gastric cancer since 1982. The patients were divided into two groups. Group 1.: Patients who had been operated radically on gastric cancer. Group 2.: Patients who had advanced gastric cancer. The following cytostatic drugs were administrated: Cyclophosphamide, Vincristine, Ftorafur. The patients who had been operated on radically were given adjuvant cytostatic treatment for 3 months according to their own protocol. The patients advanced gastric cancer got life long systemic cytostatic treatment. Between 1982 and 1989, 36 histologically proven gastric carcinoma patients were treated. The effectiveness of the therapy was measured by the survival time from the beginning of the cytostatic treatment. The control group 67 patients consisted of radically or palliative operated patients of the surgical department of those who had not got chemotherapeutic treatment. According to the experiences of the authors, the survival time was prolonged considerably by cytostatic treatment in the group of palliative operated or inoperable patients. PMID- 1866166 TI - [Relationship between histological prognostic indices and clinical course in prostatic carcinoma]. AB - The authors have summarized the relationship between histological differentiation indices and survival rate, hormonal sensitivity time, hormonal resistance time for the past 10 years. The classifications have been made according to Dhom and Gleason. 130 patients have been followed from the time of diagnosis to the time of their death. 95 patients died because of tumour. They found that there is a relationship between the survival rate and indices in those cases who were early diagnosed and they had no metastasis. There was no relationship between hormonal sensitivity time, hormonal resistance time and histological prognostic differentiation indices. PMID- 1866167 TI - [Conservative management of lymphedema of the limbs]. AB - Etiology and stadium of 63 lymphoedema patients are shown. The method of lymph drainage therapy is discussed. Important part of this treatment is bandaging. Lymphamat pump (Bosl) was successfully used as a part of the therapy. According to the good experiences it seems to be adviceable to use this method for treatment of limb lymphoedema. This method was successful in diuretics, Venoruton, Doxium and Lymph-compress resistant cases. PMID- 1866168 TI - [Primary adenocarcinoma at a colostomy site]. AB - The colostomy opening is a very rare site of the large bowel cancer. There is only one case report in the world literature and none in the Hungarian one. The authors report a case of a 51 year old man, who presented a typical malignant growth in his colostomy opening, created 24 years before due to a rectal lesion considered as an inoperable cancer, though not proved histologically. Later the patient was treated by telecobalt irradiation, and the growth perfectly disappeared. Now the second, metachron malignancy arising from the colostomy has been removed and the patient is symptom free four years after the operation. Emphasizing the importance of postoperative follow-up in cases of gastrointestinal malignancies the authors considered this case as an unique but instructive one. PMID- 1866170 TI - [Hungarian journal publishing endangered]. PMID- 1866169 TI - [Fatal hospital cases from the viewpoint of the forensic medical expert]. AB - The number of lethal cases in hospitals keeps decreasing from year to year, whereas the rate of omitted post-mortem examinations increases. The "control" role of autopsy decreases consequently. Autopsy is omitted even in cases that have been considered as possibly "extraordinary" at the beginning of the procedure and this may mean danger also from the viewpoint of criminology. According to the observations of the authors there are still uncertainties (irregularities?) concerning the tasks connected with the autopsy of those who died in hospitals, as legal injunctions are lacking. On the basis of their experiences the authors interpret the related legal measures and describe the essentials of the procedural practice considered by them correct. PMID- 1866171 TI - [Effectiveness of medical activities]. PMID- 1866172 TI - [Glucose content of blood preparations]. PMID- 1866173 TI - PNA's relationship with Nursing Foundation examined. PMID- 1866174 TI - Unlicensed nursing practice: giving our profession away. PMID- 1866175 TI - New nursing regs to impact foreign RNs. PMID- 1866176 TI - ANA releases statement on mobilization of nurses. PMID- 1866177 TI - The Cruzan decision and the right to die. PMID- 1866178 TI - The values history: an innovation in surrogate medical decision-making. PMID- 1866179 TI - Leadership--and followership. PMID- 1866180 TI - Cytoadherence of knobby and knobless Plasmodium falciparum-infected erythrocytes. AB - Cytoadherence of Plasmodium falciparum-infected erythrocytes to melanoma cells was analysed using strains or isolates of parasites expressing or not expressing knobs (K+ or K- phenotype) on the erythrocyte surface. Both K+ and K- parasites had the capacity to cytoadhere to melanoma cells. Using a panel of melanoma cell lines with different surface expression of the cytoadherence receptors CD36, thrombospondin and ICAM-1 indicated that CD36 was the major receptor for parasites of both K+ and K- phenotypes. Binding competition experiments between K+ and K- -infected erythrocytes suggested that K+ cytoadherence is of higher affinity than that of K- parasites. However, some K- cytoadherence was also found in isolates containing mixed populations of K+ and K- parasites. The interaction of the two types of infected erythrocytes with melanoma cells also differed ultrastructurally, erythrocytes of K+ phenotype showing intimate interdigitations with microvilli on the melanoma cells, while erythrocytes of K- phenotype displayed more separated interactions with fewer sites of contact and involving only a few melanoma cell microvilli. One and the same infected erythrocyte may co express the ligand for CD36-mediated cytoadherence and the structures mediating binding of uninfected erythrocytes to form rosettes. PMID- 1866181 TI - DNA probes for the detection of Babesia caballi. AB - A genomic library of Babesia caballi DNA was constructed in the plasmid vector pUC13. The specificity of the clones for B. caballi was established by the lack of hybridization to Babesia equi, Babesia bovis, Babesia bigemina and equine DNA. Two probes, pBC11 and pBC191, were isolated that could detect 0.25 ng and 0.125 ng of B. caballi DNA, corresponding to a parasitaemia of 0.12% and 0.06% respectively. pBC191 could detect B. caballi parasites in the blood of an experimentally infected horse as well as in naturally infected horses. PMID- 1866182 TI - Characterization of the lipid content of Toxoplasma gondii rhoptries. AB - Quantitative and qualitative analysis of lipids has been performed on a rhoptry fraction purified from Toxoplasma gondii tachyzoites. The lipid to protein ratio was estimated to be 0.26. The cholesterol to phospholipid ratio was unusually high at 1.48. Phosphatidylcholine was the major phospholipid; phosphatidylserine, phosphatidylinositol and sphingomyelin were absent whereas significant amounts of phosphatidic acid and lysophospholipids were found. This pelicular composition could be related to functional involvement of the organelle in host-cell invasion. PMID- 1866183 TI - An analysis of survey measurements of tsetse challenge to trypanotolerant cattle in relation to aspects of analytical models of trypanosomiasis. AB - The recent development of analytical models of trypanosomiasis has increased the general applicability of models to the strategic control of the disease. An analysis of detailed data on tsetse abundance and infection rates and trypanosome prevalence in village-based trypanotolerant cattle over 4 years in The Gambia showed that seasonal patterns of abundance in Glossina morsitans-infested areas were consistent, and that the rates of trypanosome infection remained relatively unchanging. However, there were two distinct seasonal trypanosome prevalence patterns in cattle, with peaks occurring either in May/June/July or November/December. The peaks of trypanosome prevalence therefore occurred either 4 months before or after the times of peak challenge from G. morsitans, not 1 or 2 months after as predicted by analytical models. In G. palpalis-infested areas there was little seasonal variation in abundance or trypanosome infections, but peak trypanosome prevalence still occurred mostly in June/July. Despite the incongruity between the months of peak prevalence and challenge, the overall annual prevalence rates and tsetse challenge indices showed a significant linear relationship. It is concluded that existing analytical models need to be refined to take into account trypanotolerance and the various influences on the expression of this trait. PMID- 1866184 TI - Negative effect on early post-implantation pregnancy and progesterone levels in mice infected with the intestinal trematode Echinostoma caproni. AB - Infection in mice (BALB/cABom) with the intestinal trematode Echinostoma caproni had a negative influence on pregnancy. The effect of the infection set in immediately following implantation (day 5 of pregnancy) resulting in fewer foetuses being present in infected mice on day 9 than in the controls. Ovulation, fertilization of eggs, and implantation itself were obviously not impaired. The infected mice had significantly lower serum progesterone levels on day 5 of pregnancy than the non-infected controls. It is speculated that the progesterone levels in the infected female mice were too low to secure early post-implantation gestation. PMID- 1866185 TI - Effects of temperature and host density on the snail-finding capacity of cercariae of Echinostoma caproni (Digenea: Echinostomatidae). AB - The effect of temperature (19-36 degrees C) and snail host density (0.014-10 snails/l) on the snail-finding capacity of Echinostoma caproni cercariae is described. The initial swimming speed increased whereas the length of the infective period decreased with increasing temperature. The combined effect resulted in the E. caproni cercarial snail-finding capacity being temperature independent in the range 19 to 36 degrees C at a snail density of 0.014 snails/l. A moderate temperature dependency was, however, seen at a lower snail density. The cercarial snail-finding capacity was snail-host density dependent in the density range 0.014 to 1 snail/l. The findings from this study show that a relatively low and biologically realistic snail host density must be used in experimental studies if realistic estimates of the dynamics of cercarial transmission are to be obtained. PMID- 1866186 TI - Existence of host-related DNA sequences in the schistosome genome. AB - DNA sequences homologous to the mouse intracisternal A particle and endogenous type C retrovirus were detected in the DNAs of Schistosoma japonicum adults and S. mansoni eggs. Furthermore, other kinds of repetitive sequences in the host genome such as mouse type 1 Alu sequence (B1), mouse type 2 Alu sequence (B2) and mo-2 sequence, a mouse mini-satellite, were also detected in the DNAs from adults and eggs of S. japonicum and eggs of S. mansoni. Almost all of the sequences described above were absent in the DNAs of S. mansoni adults. The DNA fingerprints of schistosomes, using the mo-2 sequence, were indistinguishable from each other and resembled those of their murine hosts. Moreover, the mo-2 sequence was hypermethylated in the DNAs of schistosomes and its amount was variable in them. These facts indicate that host-related sequences are actually present in schistosomes and that the mo-2 repetitive sequence exists probably in extra-chromosome. PMID- 1866187 TI - Site availability and density-dependent constraints on the acanthocephalan Pomphorhynchus laevis in rainbow trout, Oncorhynchus mykiss (Walbaum). AB - Threshold density levels were investigated experimentally in rainbow trout, Oncorhynchus mykiss, for the acanthocephalan Pomphorhynchus laevis. Fifty small fish 120-150 mm long were infected with 50 cystacanths each every 4 weeks for 16 weeks, and samples of up to 10 fish examined at 1, 5, 9, 13 and 17 weeks after the original infection. The mean intestinal length was found to have increased significantly over this period, from a mean of 125 to 173 mm and the mean number of parasites recovered increased after each interval of 4 weeks, and significantly from 19.30 to 86.40 per fish over the 17 weeks. The distribution of the parasites in the alimentary tract of O. mykiss was unaltered, indicating that the favourable region for establishment had remained unchanged. The failure to detect any manifestations of competition is discussed, and the relevance of conventional approaches to experimental investigations of both intra- and interspecific competition in fish was queried, and contrasted to the situation in birds and mammals. PMID- 1866188 TI - Specific immunosuppression by Trichinella: fine specificity and effect on lymphocyte function in vivo. AB - Muscle-phase Trichinella larvae depress the immune response of mice to the phosphorylcholine (PC)-bearing Trichinella antigen FCp without affecting responses to other PC-bearing or non-PC antigens. The depressive activity is independent of antigen dose and Trichinella species and, in adoptive cell transfer experiments with lethally irradiated recipient mice, depended on the state of the recipient (infected recipients had a depressed response even a month after their encysted larvae had been killed and regardless of whether the donor had been exposed to FCp) but not on the state of the transferred cells. We conclude that lymphocytes are not permanently altered by the depressive action, that the agent responsible persists in the host at least a month after the death of the encysted Trichinella larvae, and that the alteration does not eliminate lymphocyte immunological memory. PMID- 1866189 TI - Host specificity of and cross-immunity between two strains of Heligmosomoides polygyrus. AB - The infectivity of wild and laboratory strains of Heligmosomoides polygyrus (Nematospiroides dubius) in laboratory mice and in three species of wild British rodent was compared. Wild strains, of the subspecies H. p. polygyrus, were isolated from wild caught Apodemus sylvaticus. Only very low-level infections of the wild strains became established in laboratory mice. Similar worm burdens of the laboratory strain became established in laboratory mice and A. sylvaticus, although infections in A. sylvaticus were more short lived. Cortisone treatment of hosts increased the establishment and survival of the heterologous worm strain to that of the homologous strain. In contrast, neither strain of parasite established in Clethrionomys glareolus or Microtus agrestis, and cortisone treatment of C. glareolus did not increase establishment. Infection of laboratory mice with the wild-strain parasite induced significant immunity to a challenge infection with the laboratory strain. PMID- 1866190 TI - The ultrastructure and immunogold labelling of pancreatic polypeptide immunoreactive cells associated with the egg-forming apparatus of a monogenean parasite, Diclidophora merlangi. AB - An electron microscopical examination has been made of the fine structure and disposition of pancreatic polypeptide immunoreactive cells associated with the egg-forming apparatus in Diclidophora merlangi. The cell bodies are positioned in the parenchyma surrounding the ootype and taper to axon-like processes that extend to the ootype wall. The terminal regions of these processes branch and anastomose and, in places, the swollen endings or varicosities form synaptic appositions with the muscle fibres in the ootype wall. The cells are characterized by an extensive GER-Golgi system that is involved in the assembly and packaging of dense-cored vesicles. The vesicles accumulate in the axons and terminal varicosities, and their contents were found to be immunoreactive with antisera raised to the C-terminal hexapeptide amide of pancreatic polypeptide. It is concluded that the cells are neurosecretory in appearance and that, functionally, their secretions may serve to regulate ootype motility and thereby help co-ordinate egg production in the worm. PMID- 1866191 TI - Partial characterization of 2-beta-mercaptoethanol-soluble surface-associated antigens of Onchocerca volvulus. AB - Antigens were extracted from the epicuticle/cuticle of intact female Onchocerca volvulus using 2% 2-beta-mercaptoethanol and 1% SDS. In Western blot analysis a human infection serum selected for its high antibody titre against whole worm homogenates did not recognize any component solubilized by 1% SDS. However, the same serum did bind at least 7 antigens among the material extracted with 2-beta mercaptoethanol. These antigens have apparent molecular weights (Mr) of: 15,000, 18,000, 28,000, 78,000, 98,000, 120,000 and 200,000. In ELISA using this preparation as target antigen, 151 out of 153 human infection sera gave positive results. An Onchocerca-specific IgG1 monoclonal antibody, designated Cam1, recognized the 28,000 Mr antigen, which is the most prominent antigen detected by Western blot analysis using human infection sera. In ELISA, using material affinity-purified with Cam1 as target antigen, 149 out of 153 human infection sera gave a positive IgG response. From a cDNA library three expressing clones were isolated with a rabbit serum raised against 2-beta-mercaptoethanol solubilized material. One of these clones was recognized by the monoclonal antibody Cam1. PMID- 1866192 TI - N-acetylation of biogenic amines in Ascaridia galli. PMID- 1866193 TI - Five years survival of 1112 patients with cancer of the breast: prognostic value of clinico-morphological parameters including the histochemically evaluated receptor status. An Italian cooperative study. AB - In 1112 patients operated for carcinoma of the breast in 13 different Italian Institutions between 1980 and 1984, and then coded according to several traditional parameters and to the histofluorescent evaluation of the estrogen receptor status (Rf test), by the end of 1988 there were 245 deaths related to cancer and 52 deaths for unspecified cause. Mortality increased from 13 to 83% from stage 1 to stage 4. Within stage 1 and 2 survival was related to the tumor size and the extent of lymph-node involvement. The prognosis was significantly worsened on the whole series (but not on N--patients) when the tumor had irregular borders, more than one nodule and it was angioinvasive. The Rf test had a long lasting prognostic value only if positive in more than 50% of the neoplastic cells, especially in stages 1 and 2, in patients younger than 35 and in the perimenopausal age, in tumors smaller than one cm. and larger than two cm. even with lymph-node involvement. PMID- 1866194 TI - [Tumor grading in urinary cytology. A study of the cytohistological relationship with evaluation of the kappa statistic for concordance]. AB - In order to verify both usefulness and reliability of cytologic grading evaluated on urinary sediment, we designed a study to test the ability to distinguish consistently between different degrees of neoplastic abnormalities of urothelial cells from voided urine, in relation to the histologic findings of bladder biopsies performed after cytologic reading. Kappa measures were calculated in 112 cytohistologic pairs representative of first disease detection (A) and in 35 pairs representative of disease recurrence (B). Cytology was able to correctly identify a cancer in 70.5% and 80.0% of group A and group B lesions, respectively. Unweighted kappa values of both groups A and B were poor (0.298 and 0.324 respectively). When we considered the weighted kappa, values suggesting fair agreement were obtained (0.576 and 0.500). Our data confirm that urinary cytology shows a good sensitivity in detecting bladder cancer, but it does not seem to give reliable results for the assessment of the tumor grading. PMID- 1866195 TI - [Identification of mucin-secretion characteristics in cells from serous effusions: consideration of histochemical and immunohistochemical aspects]. AB - Fourty-two cell-blocks of serous effusions (thirty malignant and twelve reactive) were tested by anti Secretory Component Ab (policlonal) using the s.-Ab method, and by histochemical tests: PAS, PAS Diastase and Alcian blue pH 2.5. Immunohistochemical and histochemical features were compared to identify their meaning and correlation in epithelial mucin detection. This study suggests the evident correlation between SC and PAS diastase (better than between SC and Alcian blue) and possibility to replace the old traditional test of PAS diastase with anti SC antibody (much more sensible than PAS diastase) in routine mucin detection histochemical tests. PMID- 1866196 TI - [Human pulmonary dirofilariasis. A third case in Italy]. AB - A new case of Human Pulmonary Dirofilariasis, the third in Italy, is described. It occurred in August 1990 in a 66 years old man, living in San Dona di Piave (province of Venice). The pulmonary infarctual lesion caused few symptoms and was discovered by chance during a chest X-ray examination as a coin lesion and suspected to be of a neoplastic origin. The histological findings allowed the exact diagnosis, identifying the causal agent as Dirofilaria probably repens, a nematode common parasite of dogs in the Old World and recognised agent of over 90 human cases of Subcutaneous Dirofilariasis reported in Italy. The parasite was an immature male in advanced regressive conditions. It was inside the lumen of a small artery, surrounded by necrotic-phlogistic tissue with granulomatous giantcellular aspects of the foreign body type. Some questions are raised by the authors in relation to the presence of human cases by D. repens and not by D. immitis (dog heartworm) in areas of Italy where this last species is much more prevalent than the former in canine populations; to the fact that the 3 Italian pulmonary cases (which are the only ones reported in Europe) happened in the same restricted geographic area (Veneto and Emilia-Romagna regions); and finally to the fact that all the 3 cases occurred in elderly people. PMID- 1866197 TI - [Melanoma of the lower female urogenital tract (gynecological melanoma)]. AB - Eight cases of melanoma of the lower female urogenital tract are presented. The lesions were located 5 in the vulva, 2 in the vagina and 1 in the urethra. Patients had a mean age of 58.3 (range 43-80). Most of vulvar melanomas were polypoid and black, 3 of them arose in the major labium, 2 in clitoris area; histologically, four tumors were superficial spreading melanomas and one unclassifiable. Grossly, one vaginal melanoma was nodular, one polypoid, both were black and arose in the lower vagina. Urethral melanoma arose in the distal part of the organ. Prognosis of gynecological melanoma is severe, as 5 out of 8 patients died in 5-52 months. PMID- 1866198 TI - [A quantitative analysis of nucleolar organizer regions (NORs) in renal adenocarcinoma]. AB - A quantitative analysis of nucleolar organizer regions (NORs) in renal adenocarcinoma is proposed. The NORs have been evaluated on paraffin sections by a silver staining methods. A series of 19 renal adenocarcinoma is tested. A significant statistical difference (P less than 0.001) is found between normal and neoplastic tubules and between different stages of neoplasia. The authors suggest that this method if supported by authors date, may be a new prognostic index. PMID- 1866199 TI - [Receptor assessment of primary breast carcinoma and synchronous metastatic lymph nodes: histochemical study]. AB - Several AA, utilizing the biochemical method (DCC) showed the presence or absence of hormonal receptor in either synchronous or metachronous metastatic nodes (N) can reproduce the receptor assessment (AR) of the primary breast tumor (T). We evaluated the AR in T and in synchronous N, by using two morphological methods, immunocytochemical and histofluorescent, to detect the nuclear Estrogen Receptor (ER1) and cytoplasmic sites of the II type (ER2 and PgR2). We studied 50 patients who underwent radical mastectomy for breast cancer N+. In this series we founded a high correlation between AR in T and in N: 82% for ER1, 94% for ER2, and 92% for PgR2. Also we observed 4 cases (2 ER1 and 2 PgR2) which presented the receptor in N only. These data are comparable to results obtained with the DCC method and confirm the opportunity to perform also morphological techniques to evaluate AR in breast cancer to take into consideration also cellularity and tumor heterogeneity informations. PMID- 1866200 TI - [Evolution of acute leukemia in myelodysplastic syndromes: prognostic histopathological factors in a series of bone marrow biopsies]. AB - Out of 9,324 bone marrow biopsies, 250 cases of myelodysplastic syndromes (MDS) and 514 of acute non-lymphoid leukemia (AL) were collected. Twenty AL represented an evolution of MDS: the marrow had a mean cellularity of 58.5%, a mean percentage of blasts of 19% (55% of the cases had more than 10% of blasts in the marrow); only in one case (5%) benign lymphoid nodules (LN) were present. In 42 cases of MDS deceased without an evolution to overt AL, the bone marrow showed a cellularity of 60%, a mean percentage of blasts of 14% (only 29% had more than 10% of blasts); in 13 cases (31%) LN were present. Our data indicate that the percentage of bone marrow blasts is the most significant criterion for predicting an evolution to AL, although in the single case such evolution is not foreseeable. The presence of LN mostly in MDS without a leukemic progression could indicate a protective effect of NL, perhaps by means of an immunologic mechanism. PMID- 1866201 TI - Splenic morphological changes in acute peritonitis: experimental observations in rats. AB - In course of acute bacterial peritonitis in rats, the authors observed an active role of the macrophages of the spleen, well explaining the important defensive function of this organ against infection. PMID- 1866202 TI - [Cystic adventitial disease (histopathological contribution of a case in the ilio femoral region)]. AB - Cystic adventitial disease is a rare vascular pathology mostly affecting the popliteal artery in disease is a rare vascular pathology mostly affecting the popliteal artery in men. An unusual case, located in the ilio-femoral region of a young woman, is reported. The authors claim that the cystic adventitial formations are similar to the ganglia that originate from tendon-sheaths, as structure, configuration and, probably, histogenesis are concerned. Moreover the authors suggest that cystic adventitial disease can be located among "histogenic dystrophic arteriopathies" in the pathokinetic classification of angiopathies. PMID- 1866203 TI - [Embryonal rhabdomyosarcoma of the eye: cytological diagnosis by fine needle aspiration]. PMID- 1866204 TI - [Primary isolated lymphoma of the liver: rapid cytological diagnosis by fine needle aspiration biopsy]. AB - A case of primary hepatic lymphoma diagnosed with rapid staining of smears of material collected with echo-guided FNAB is described. The primary isolated lymphoma of the liver is a rare disease and forty reported cases since 1989 have been reviewed in the literature; many of which were first diagnosed at autopsy or shortly before death. Due to the rarity of the primary hepatic lymphoma, a large list of differential diagnosis has to be considered and they all fall into the category of malignant small cell tumors: moreover a definitive diagnosis may be sometimes impossible in a small needle biopsy. In the reported case the importance of a unique morphological feature (lymphoglandular bodies) is discussed in order to stress the easier diagnosis of lymphoproliferative disease allowed on cytological preparations vs. histological ones. PMID- 1866205 TI - [Utility of morphometry and nucleolar organizer regions count in the differentiation of reactive and malignant mesothelial cells in pleural effusions]. AB - The authors have evaluated in eight reactive and eight malignant pleural effusions the number of intranucleolar dots representing the nucleolar associated proteins stained with silver colloid technique (interphase nucleolar organizer regions-AgNOR). The mean number per nucleus in benign reactive mesothelium was significantly lower than in mesothelioma effusions. Other morphometric measurements of nuclear diameters and areas were effected. The authors evaluate the variability of the AgNOR counts and morphology in reactive and mesothelioma cells of pleural fluids. PMID- 1866206 TI - Use of monoclonal antibody B72.3 as a marker of metastatic carcinoma cells in neoplastic effusions. AB - The value of monoclonal antibody B72.3 as a diagnostic discriminator between mesothelioma and carcinoma cells in malignant effusions was assessed using the ABC method in a series of cell blocks prepared from centrifuged fluids. These were obtained from either pleural or peritoneal neoplastic effusions in patients with histologically verified malignant mesothelioma (n:10) or carcinoma (n:20). Reactivity with MAb B72.3 in at least 10% or more of tumour cells was found in 16 (80%) out of 20 metastatic carcinoma, whereas 2 mesotheliomas displayed positive immunostaining in less than 5% and approximately 20% of the malignant cells respectively. Reactive mesothelial cells were consistently non-immunostained. These results suggest that B72.3 positivity in greater than 10% of tumour cells is certainly indicative, but not absolutely diagnostic, of a metastatic origin of malignant effusions. PMID- 1866207 TI - Enhanced lung maturation in cocaine-exposed rabbit fetuses. AB - Because of cocaine's possible effect on the incidence of respiratory distress syndrome in offspring of cocaine-addicted mothers, we have studied the effects of maternal exposure to cocaine on the functional anatomy of fetal rabbit lungs. Pregnant dams were injected s.c. daily with either cocaine (18 mg/kg) or an equal volume of 0.9% NaCl at 24, 25, and 26 d gestation. Cocaine metabolites were confirmed both in urine of treated dams and in fetal amniotic fluid. Serum cortisol levels were higher in treated dams than in controls. Fetuses were delivered through hysterotomy at 27 d. Tracheas were cannulated and a volume pressure diagram was obtained during initial lung inflation-deflation. Volume was measured for 2 min at each pressure (P) increment of 5 cm H2O. Body weights and dry lung weights were comparable between the two groups. In contrast, cocaine exposed lungs differed from controls as follows: 1) wet lung weights were lower (0.79 versus 0.89 g, p less than 0.02); 2) opening pressure was lower (P25 versus P35); 3) volume (mL/kg) was higher in treated animals at each pressure step (p less than 0.05); 4) end-deflation volume at P0 was higher (30.4 versus 0.8 mL/kg, p less than 0.001); and 5) bubbles released from saccules by micropuncture, which were stable by Pattle's criteria, had estimated surface tension near zero (controls produced no stable bubbles). Light micrographs of cocaine-exposed fetuses revealed more secondary septa and thinner septal walls than controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866208 TI - Endothelium-derived relaxing factor: evidence that it regulates pulmonary vascular resistance in the isolated neonatal guinea pig lung. AB - Endothelium-derived relaxing factor (EDRF), believed to be nitric oxide or a compound that releases nitric oxide, has been previously identified in the pulmonary and systemic vasculature of the newborn guinea pig using isolated arterial rings. The aim of our study was to determine if EDRF regulates vasomotor tone at the level of resistance vessels in the neonatal pulmonary circulation. Isolated lungs from guinea pigs (1-3 d old, n = 4-8/protocol) were ventilated with room air and perfused with a Krebs-Henseleit solution containing albumin at a constant flow. Angiotensin II (AII, 6 nM) was added to the perfusate to give a stable elevation in mean pulmonary artery pressure (PAP) from 7.0 +/- 1.1 to 19.7 +/- 1.5 torr, a 182 +/- 32% (mean +/- SEM) increase above baseline. Addition of bradykinin (BK, 10 nM) or L-arginine (2 mM) markedly reduced the AII-induced elevation in PAP. At the steady state response to BK (33% above baseline), addition of Hb (10 microM, binds EDRF), NG-monomethyl-L-arginine (NMA, 100 microM, blocks EDRF production), NMA (200 microM), or NMA + Hb, reversed the effect of BK to the following levels of PAP above baseline: 77 +/- 5, 94 +/- 24, 163 +/- 20, or 246 +/- 25%, respectively (p less than 0.05). Indomethacin had no effect on BK-induced vasodilation. In separate studies, NMA (200 microM) increased baseline PAP by 46 +/- 13% and NMA pretreatment raised the AII-pressor response (AII 6 nM) from 133 +/- 49 to 306 +/- 65% above baseline PAP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866209 TI - Reactive oxygen metabolites produce pulmonary vasoconstriction in young pigs. AB - Reactive oxygen metabolites appear to modulate pulmonary vascular changes. To study the effects of free radical formation in vivo, we investigated five groups of young pigs by recording hemodynamic changes after xanthine oxidase infusion alone and after pretreatment with hypoxanthine or possible blocking agents. The pulmonary vascular pressure increased rapidly in the groups without inhibition reaching maximum levels 25 min after the start of the experiment. The pulmonary artery blood flow declined toward minimum values at the same time. Compared to baseline levels, the calculated vascular lung resistance increased by 300% when the pigs were pretreated with hypoxanthine, and by 150% when xanthine oxidase was given alone. These findings suggest enhanced pulmonary vasoconstriction as a result of high initial hypoxanthine levels probably capable of forming larger quantities of oxygen radicals. The vascular reaction was attenuated when the pigs were pretreated with indomethacin (cyclo-oxygenase inhibitor) or allopurinol (xanthine oxidase inhibitor). Furthermore, the presence of catalase (hydrogen peroxide scavenger) reduced the pulmonary vasoconstriction significantly. We observed less decline in arterial oxygen tension and oxygen saturation when the animals had been pretreated with inhibitory agents, compared to the blood gas changes found in the xanthine oxidase group. The systemic pressure recordings in the carotid artery remained at baseline levels in all groups. We conclude that oxygen radicals formed by the hypoxanthine-xanthine oxidase system produce severe pulmonary vascular constriction in young pigs. PMID- 1866210 TI - Respiratory effects of lactic acid injected into the jugular vein of newborn rabbits. AB - To define respiratory effects of peripheral acidemia during early development, we injected lactic acid (LA) into the jugular vein of 32 1- to 7-d-old rabbit pups and four adult rabbits. The body weight of newborns varied between 67 +/- 17 g in 1-d-old and 119.8 +/- 33.7 g in 7-d-old animals versus 4 +/- 0.1 kg in adults. Animals were anesthetized with ketamine (30 mg/kg) and urethane (0.6-1.2 g/kg), tracheotomized, and breathed spontaneously. Diaphragmatic electromyogram, tidal volume, esophageal pressure, and arterial pressure were recorded. In adult rabbits, a LA dose of 0.25 mM/kg elicited an increase in the rate of breathing with no change or a decrease in tidal volume (early response), followed by a deep and fast respiration (late response). The same LA dose had no effect or provoked only the late response in 1- and 2-d-old rabbits and led to the early and late responses in older newborns. The early response was abolished and the late response was diminished after vagotomy. Our results suggest that the early response is mediated by vagal afferents and the late response, although modified by vagal input, is of an extravagal origin. It is suggested that acidemia may be involved in the transient tachypnea syndrome in newborn infants. Possible contribution of vagal nonmyelinated endings in triggering the early response to LA is discussed. PMID- 1866211 TI - Dexamethasone prevents hypoxic-ischemic brain damage in the neonatal rat. AB - Glucocorticoid therapy is frequently used in perinatology and neonatology for its beneficial pulmonary effects. We investigated the influence of neonatal glucocorticoid administration on brain damage caused by a concurrent episode of cerebral hypoxia-ischemia. Various doses of dexamethasone in several treatment schedules were administered to 7-d-old rats that were also subjected to unilateral cerebral hypoxia-ischemia. In 79% of control rats, a large unilateral cerebral infarction occurred, whereas all rats pretreated with dexamethasone in doses of 0.01 to 0.5 mg/kg/d for 3 d had no infarction (p less than 0.001). The neuroprotective effect of dexamethasone pretreatment was dose- and time dependent. Treatment with dexamethasone after the insult or with lower doses before the insult did not prevent infarction. The neuroprotective effect was not immediate: single doses 0 to 3 h prehypoxia were not effective but a single dose 24 h before hypoxia-ischemia prevented cerebral infarction. The results demonstrate that glucocorticoid administration in the neonatal period, even in low doses, protects the brain during subsequent periods of hypoxia-ischemia. PMID- 1866212 TI - Nondeformable red blood cells do not interfere with uteroplacental blood flow in the awake, late-pregnant guinea pig. AB - The fractional entrapment of rigidified [relative to control (labeled)] red cells after the intravascular bolus injection of a cocktail of these cells, and the concomitantly induced changes in cardiac output and its distribution (microspheres) were studied in 14 awake, late-pregnant guinea pigs. In a preceding validation study in eight nonpregnant guinea pigs, it was demonstrated that with this technique reproducible data could be generated on the fractional entrapment of rigidified red cells in all organs in this species except for lungs, liver, and spleen. In response to a bolus injection with rigidified and control red cells, only the brain showed preferential entrapment of rigidified red cells, together with a small but consistent increase in blood flow. In other organs (lungs, liver, and spleen excluded), neither preferential entrapment of rigidified red blood cells nor a consistent change in blood flow could be demonstrated. The results of our study suggest that circulating nondeformable red cells have no measurable adverse effect on the perfusion of the nondiseased hemochorial placenta in the awake, late-pregnant guinea pig. This does not exclude the possibility that rigidified red cells may increase the resistance to flow in a microcirculation that has been pathologically changed by some underlying disease. PMID- 1866213 TI - Patent ductus arteriosus, indomethacin, and intestinal distension: effects on intestinal blood flow and oxygen consumption. AB - To determine the relative importance of patent ductus arteriosus, indomethacin, and intestinal distension as factors that promote terminal ileum ischemia, eight near-term fetal lambs were surgically prepared by in situ cannulation of the proximal and distal ends of a loop of terminal ileum, formalin infiltration of the ductus arteriosus, and placement of a snare around the ductus arteriosus to control its patency. The incisions were closed; the lambs were delivered and mechanically ventilated. Terminal ileum blood flow and oxygen consumption were measured after the loop of ileum had been distended with 0.9% NaCl to luminal pressures of 1-2, 7, and 18 mm Hg (0.13-0.26, 0.93, and 2.38 kPa) (pressures observed in the intestinal lumen after feeding and during pathologic conditions). The effect of these pressures on terminal ileum blood flow and oxygen consumption was examined: 1) with ductus closed, 2) with ductus open, and 3) 1 h after administration of indomethacin (0.3 mg/kg; 0.8 mumol/kg) with ductus closed. Both open ductus and indomethacin produced a significant decrease in intestinal blood flow. This occurred over the entire range of luminal pressures examined. In all three study conditions, terminal ileum blood flow fell commensurate with a fall in perfusion pressure. Despite this absence of pressure-flow autoregulation, oxygen consumption was maintained when the ductus was closed or open. In contrast, indomethacin inhibited the ability of the terminal ileum to autoregulate its oxygen consumption. These findings suggest that both open ductus and indomethacin present an increased risk of intestinal ischemia. We hypothesize that indomethacin's beneficial effect on ductus closure may be counterbalanced by its negative effect on intestinal perfusion and metabolism. PMID- 1866214 TI - Heart rate recovery from 1 minute of exercise in children and adults. AB - Previous studies demonstrated that the time required for oxygen uptake, CO2 production, and minute ventilation to return to baseline levels after 1-min bursts of exercise is different in children compared with adults. To test the hypothesis that the heart rate (HR) recovery time after exercise is also different in children compared with adults, we examined HR in 10 children (range 7-11 y old) and 12 adults (26-42 y old) for 10 min after 1 min of cycle ergometer exercise. Each subject exercised at work rates corresponding to 80% of the lactate or anaerobic threshold (AT), 50% of the difference between AT and maximal O2 uptake (delta), 100% of maximal uptake, and 125% of maximal uptake. Gas exchange was measured breath by breath. In adults, the HR recovery time increased significantly with work intensity as judged by the time constant of a single exponential curve fit to postburst-exercise HR [23 +/- 8 (SD) s at 80% AT, 55 +/- 16 at 50% delta, 74 +/- 13 at 100% of maximal uptake, and 83 +/- 20 at 125% of maximal uptake]. HR recovery time tended to increase with work intensity in children (16 +/- 7, 20 +/- 4, 23 +/- 7, and 27 +/- 9; for 80% AT, 50% delta, 100% of maximal uptake, and 125% of maximal uptake respectively), but to a much smaller extent, and the HR recovery time was significantly smaller in children in the high-intensity (above AT) range of exercise (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866215 TI - Troponin T expression in normal and pressure-loaded fetal sheep heart. AB - The effects of cardiac hypertrophy in adult animals on the expression of a number of genes are well established. There is, however, a paucity of information about the effect of pressure overload on the expression of genes coding for the contractile proteins in the prenatal developing heart. The prenatal cardiac muscle can increase cell number in response to stress, whereas the adult heart increases cell mass. Thus, the response of the fetal heart to pressure overload cannot be assumed to be identical to that of adult myocardium. We studied the effect of banding the great vessels of fetal sheep hearts on the expression of troponin T (TNT). In other vertebrates, TNT mRNA is generated by alternative splicing of a primary transcript. Thus, both the levels and patterns of TNT isoforms generated by alternative splicing in the heart could be influenced by pressure overload. The techniques of cDNA library screening and polymerase chain reaction were used to define the influence of in utero banding of the great vessels on TNT expression. The data indicate that there is a single dominant isoform of TNT expressed from mid-gestation to adult life in sheep. The pattern of TNT isoform expression in the sheep heart proved to be unique among all animals studied to date. PMID- 1866216 TI - The incorporation of n-3 and n-6 essential fatty acids into the chick embryo from egg yolks having vastly different fatty acid compositions. AB - The effect of egg yolk fatty acid composition on essential fatty acid utilization by the developing chick embryo was studied by feeding laying hens a fat-free diet supplemented with oils containing widely divergent contents of the essential n-6 and n-3 fatty acids. A control hen was fed a commercial feed for laying hens. The diets contained 20 to 4370 mg/100 g n-3 fatty acids and 360 to 8020 mg/100 g n-6 fatty acids. Fertile eggs were collected in pairs: one was incubated and the other served as an unincubated control. The fatty acid content of the unincubated egg and the newly hatched chick from each pair was compared. Some 50% of the total fatty acids in the egg yolk were incorporated into the tissues of the newly hatched chick. Regardless of diet, more yolk n-6 fatty acids were incorporated into the chick compared to saturated or monounsaturated fatty acids. The percentage of incorporation especially increased from the eggs containing relatively low amounts of n-6 fatty acid. The percentage of incorporation of n-3 fatty acids was similar to that of saturated and monounsaturated fatty acids when n-3 fatty acids were plentiful in the egg yolk, but increased significantly when n-3 fatty acids were low in the eggs. There was a generally linear relationship between essential fatty acids in the egg and in the chick, although levels of docosahexaenoic acid [DHA; 22:6(n-3)] in the brain did not respond proportionally.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866217 TI - The cross-generation effect of neonatal macrosomia in rat pups of streptozotocin induced diabetes. AB - To study the cross-generation effect of enhanced growth in macrosomic newborn rats, we induced mild hyperglycemia in 15 pregnant Sprague Dawley rats by intraperitoneal injection of streptozotocin, 35 mg/kg body weight, on the 5th d of gestation. As reported previously, we produced hyperinsulinemia and accelerated growth in the fetuses of hyperglycemic dams. We also showed that the macrosomic female pups (second generation) continued to have a higher growth rate through the first 12 wk of life. In this study, the second-generation female rats were mated with macrosomic second-generation males; they demonstrated glucose intolerance during late pregnancy and delivered pups (third generation) with higher birth weight and plasma insulin levels than the pups from control second generation rats. When the macrosomic third-generation pups were raised under identical nutritional and environmental conditions as controls, the macrosomic rats showed accelerated growth and higher fat tissue weight during the first 12 wk of life. Furthermore, the macrosomia was associated with glucose intolerance and higher insulin to glucose ratios compared to controls. We also mated the offspring of second-generation streptozotocin-injected nonmacrosomic as well as the offspring of macrosomic pups of buffer-injected dams; none of the pups from these matings were significantly macrosomic. Therefore, we conclude that the perpetuation of obesity and possibly glucose intolerance across generations in this rat model is predominantly a result of abnormal intrauterine metabolic environment rather than genetic factor driven. PMID- 1866218 TI - Insulin receptor number and binding affinity in newborn dogs. AB - The insulin resistance in newborn mammals may be caused by a receptor or postreceptor defect. Although liver and umbilical cord blood monocytes have increased numbers of insulin receptors, there is a paucity of information about other neonatal tissues. Glucose disposal takes place primarily in the skeletal muscle; therefore, it is important to evaluate this tissue for an insulin receptor defect. To determine the role of insulin receptors in neonatal insulin resistance, neonatal and adult canine skeletal muscle, heart, and liver were compared for numbers of insulin receptors and their affinity for insulin. Partially purified receptors from four animals in each group were obtained by wheat germ lectin affinity chromatography and used in competition binding studies. Specific binding (mean +/- SE) in the absence of cold insulin was increased in newborn skeletal muscle (9.7 +/- 0.8 versus 4.8 +/- 0.5%, p less than 0.001) and heart (8.1 +/- 1.2 versus 5.5 +/- 0.6%, p less than 0.05). High affinity insulin receptor number (mean +/- SEM) was increased in newborn skeletal muscle (183 +/- 40 versus 120 +/- 29 pM, p less than 0.002) and heart (264 +/- 94 versus 157 +/- 51 pM, p less than 0.05) as estimated from the X intercept of the Scatchard plot. Using half-maximal binding to estimate affinity, there were no differences between adults and newborns among all tissues studied. High-affinity receptor number and percentage of specific binding were similar for newborn and adult liver tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866219 TI - Dual tracer stable isotopic assessment of calcium absorption and endogenous fecal excretion in low birth weight infants. AB - Using a dual tracer (44Ca orally and 46Ca i.v.) stable isotope technique, true dietary Ca absorption, endogenous fecal Ca excretion, and net Ca retention were measured in 12 low birth weight (1426 +/- 260 g) infants fed a high Ca-containing formula. Endogenous fecal Ca excretion averaged 7.2 +/- 4.1% of intake, and exceeded 10% of intake in three infants. Net Ca retention, 103 +/- 38 mg/kg/d, was consistent with previous studies of Ca retention obtained using mass balance techniques and correlated closely (r = 0.98, p less than 0.001) with true Ca absorption but not with endogenous fecal excretion (r = -0.40, p = 0.19). Although endogenous fecal excretion may represent a significant source of Ca loss for some low birth weight infants, these data suggest that net Ca retention in low birth weight infants fed a high Ca-containing formula is primarily determined by the total dietary Ca absorbed. PMID- 1866220 TI - Diagnostic significance of urinary growth hormone measurements in children with growth failure: correlation between serum and urine growth hormone. AB - Twelve-h overnight urine and serum samples obtained simultaneously at 20-min intervals were assayed for growth hormone (GH). Ninety-one children, 5 to 16 y (Tanner stage 1 to 3) participated; group 1 were healthy children, group 2 were children with organic GH deficiency, and group 3 had idiopathic growth failure and normal GH stimulation tests. Serum pool GH concentrations in group 1 were similar to those in group 3 (3.3 +/- 0.3 versus 3.4 +/- 0.2 micrograms/L); group 2 had significantly lower GH concentrations (1.6 +/- 0.2 micrograms/L). Plasma IGF-I levels were significantly greater in groups 1 (14.2 +/- 2.6 nmol/L, p less than 0.001) than in groups 2 and 3 (2.6 +/- 0.5 and 5.5 +/- 0.7 nmol/L, respectively). Urinary GH (mean +/- SEM) standardized for body weight (micrograms/kg) in group 1 (0.31 +/- 0.02) was significantly greater than in group 2 (0.14 +/- 0.01) and group 3 (0.20 +/- 0.01). However, when expressed as microgram/mol creatinine, the output of GH was similar in group 1 (4.0 +/- 0.3) and group 3 (3.4 +/- 0.3); both groups had significantly greater output compared to group 2 (1.3 +/- 0.2). Urinary IGF-I (nmol/kg) in group 1 (0.22 +/- 0.02) was significantly greater than in group 2 (0.12 +/- 0.01) or group 3 (0.07 +/- 0.01). Urinary GH correlated with serum pool GH concentration (r = 0.64, p less than 0.001). Although urinary GH output reflects endogenous GH secretion, the overlap between groups 1 and 3 precludes using urinary GH measurements as a diagnostic test for GH deficiency in children with idiopathic growth failure. PMID- 1866221 TI - Reduction in plasma protein does not affect body water content in fetal sheep. AB - We performed this study to determine if isolated hypoproteinemia and low colloid osmotic pressure cause formation of fetal edema. We successfully operated on six sets of twin fetal sheep at 114 d gestation to insert catheters into arteries and veins of both fetuses, allowing us to chronically perform partial exchange transfusions. One twin underwent protein reduction by repeated partial exchange transfusion over 3 d, and the other twin underwent simultaneous sham procedures. We removed an average of 18 g of protein, causing a 41% decrease in plasma protein concentration and a 44% decrease in colloid osmotic pressure. Vascular pressures, heart rate, hematocrit, plasma osmolarity, arterial pH, and arterial PO2 were not affected by protein reduction or by sham procedure, whereas PCO2 increased by a small amount in both groups. At autopsy, none of the fetuses in either group were edematous. Measurements of total body water by the wet to dry method, chloride space, and amniotic and allantoic fluid volumes were similar in both groups. We conclude that hypoproteinemia of a short duration does not affect the body water content of fetal sheep. PMID- 1866222 TI - [Health status in young institutionalized children]. PMID- 1866223 TI - [Involvement of blood vessels and hemodynamics in children with rheumatoid arthritis and systemic lupus erythematosus]. PMID- 1866224 TI - [Characteristic of endocrinopathies in children and adolescents with socio psychological deprivation]. PMID- 1866225 TI - [Physical development and psychoemotional status of Soviet children, temporary living in Mongolia]. PMID- 1866226 TI - [Lipids peroxidation in children with atopic dermatitis]. PMID- 1866227 TI - [Effectiveness of antioxidant inhalation in children with bronchial asthma]. PMID- 1866228 TI - [Effect of initial autonomic tonicity on the results of reflexotherapy in children with chronic gastritis]. PMID- 1866229 TI - [Evaluation of the effect of vitamin E on the fetus and newborn baby]. AB - The authors studied the effect of vitamin E administered antenatally in view of miscarriage on the body of the fetus and newborn. Experiments made on albino rats, their fetuses and newborn rats demonstrated an increase of the mass of the newborn and their organs together with a greater morphofunctional maturity and higher content of vitamin E in the body. Administration of vitamin E to pregnant women also provided a beneficial effect: a favourable course of the neonatal period, a milder course of diseases that occurred, and a high level of natural antioxidants in the children's body. PMID- 1866230 TI - [Hormonal diagnosis of endocrinopathies in the early neonatal period]. AB - Based on the summarization of the results of hormonal examination of the newborn during the early neonatal period it has been revealed that early diagnosis of endocrinopathies can only be made with the use of the laboratory measurements of the concentrations of the appropriate hormones. For early diagnosis of congenital endocrine diseases the screening made according to the specific hormonal test is the most effective approach. It is necessary to differentiate between alterations associated with congenital endocrine diseases and transitory hormonal reactions due to the derangement of the child's status in the ante-, intra- or postnatal periods. PMID- 1866232 TI - [Microbial biocenosis in normal newborn babies and in septic diseases]. AB - A study was made of the symbion microflora of different biotopes in 185 neonates with sepsis and 200 healthy neonates on natural feeding. Appreciable differences were revealed in the formation of the microbial ecosystems in children with sepsis as compared to the healthy neonates. In the septic process the microbiological profile for different biotopes is poorly differentiated and is characterized by the similarity of opportunistic bacteria isolated. The children who suffered pyoseptic pathology need additional bacterial therapy aimed at the recovery of the normal microflora. PMID- 1866231 TI - [Hormonal regulation of glycemia and metabolic adaptation of newborn babies with intrauterine hypotrophy]. AB - The content of hormones that regulate carbohydrate metabolism was studied during the early neonatal period in 80 full-term neonates with intrauterine hypotrophy. Early application to the breast (2 to 6 hours after the birth) was shown to promote the normalization of the hormonal content. The levels of blood serum C peptide in the newborn depend on the degree of the rise of the mother's body weight during pregnancy and the presence of toxicosis. The levels of cortisol, somatotropic hormone, immunoreactive insulin and C-peptide were determined by the degree of morphological immaturity of the tissues whereas the content of STH and cortisol by the intensity of hypotrophy as well. The moment of the birth and the early neonatal period of children with intrauterine hypotrophy is characterized by a decrease of the activity of lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, creatine kinase and aspartate aminotransferase. PMID- 1866233 TI - [Enzyme status of blood cells in premature children during the treatment of omphalitis by helium-neon laser radiation]. AB - Helium-neon laser radiation was employed in the treatment of 27 premature children suffering from omphalitis. It has been established that helium-neon laser radiation produces a favourable effect on the healing and epithelization of the umbilical wound, activates lymphocyte succinate dehydrogenase in premature children. The rate of wound healing correlates with the initial enzymic status, with the number of sessions of laser therapy and the general estimation of the previous development of the child in accordance with the prognostic coefficient of sepsis development. PMID- 1866234 TI - [Medium-weight molecules in the determination of the level of endogeneous intoxication in newborn babies]. AB - Criteria for the diagnosis of the syndrome of endogenous intoxication were specified in neonates in a critical condition because of pathology of the early neonatal period. It has been established that early diagnosis of toxicosis is promoted by the determination of the pool of medium-weight molecules, the growth of which precedes the clinical picture manifestation. The totality of the indicators of the content of medium-weight molecules and the leukocytic index of intoxication determine the type of toxicosis (infectious, hypoxic, traumatic), predict its course and outcome, being an alternative in the choice of methods for body detoxifying. PMID- 1866235 TI - [Clinico-hemostatic features in premature infants with hypertensive hydrocephalic syndrome]. AB - The authors relate the results of studying certain indicators of hemostasis in 42 premature children of the first year of life seen for the hypertensive hydrocephalic syndrome at the Neonatality Center. A relationship has been discovered between the coagulogram and the degree of the child's maturity at birth, the age, and initial disease. PMID- 1866236 TI - [Children morbidity in the first 3 years of life in the family]. AB - The purpose of the study was to explore in detail the health status of children of the first three years of life. As many as 450 children born in 1977-1981 were examined. It has been established that the children's morbidity in the following life periods is influenced by the time of the first disease onset and social and hygienic conditions of the child's life. PMID- 1866237 TI - [Persistence of opportunistic Staphylococcus and disorders of immune homeostasis in frequently sick children]. AB - Clinical, microbiological and immunological examinations were made of ailing children with localized (fauces) and spread (fauces, skin, intestine) staphylococcal lesions. The clinicogenealogical analysis revealed considerable hereditary aggravation as regards immune pathology, the presence of immunopathological diatheses, and a high level of dysembryogenesis stigmas in the given children's group. S. aureus and S. epidermidis were identified. In ailing children, the authors proved the persistence of ubiquitary staphylococcus, giving rise to the deficiency of immune factors consumption as related to the characteristics of antigenic adaptation of such children. Immunologic tolerance was found to fail at one of the crucial periods of immunity, with the opsonocytophagic component appearing to be the site of application of the suppressant action of Staphylococcus. PMID- 1866238 TI - [Today's problems of medical care for low birth weight infants]. PMID- 1866239 TI - [Incidence of immune deficiency in children population from industrial city]. AB - The authors relate the data on the incidence of different forms of immune deficiency (ID). The studies were carried out within the framework of the All Union program of mass immunoepidemiological screenings, among the childhood population of industrial city numbering 59,178 persons. The primary group at ID risk amounting to 2.2% was distinguished. Based on the clinico-anamnestic data a group at higher ID risk was made up (n-421). 450 children were examined by the level I tests. The children were characterized clinicoimmunologically according to different immunopathological syndromes. All the children with the identified forms of ID and those without well-defined forms of immunodeficiency conditions but with steady alterations of the immunologic parameters and the clinical signs need prophylactic medical examinations. PMID- 1866240 TI - [Neuropeptides in atopic dermatitis in children]. AB - Radioimmunoassay was used to measure the blood plasma content of endogenous opioid peptides (beta-andorphine, methionin- and leucine-enkephalins), R substance, calcium-regulating hormones (parathyroid hormone and carcitonin), ionized calcium and cortisol in 152 children aged 6 months to 12 years with atopic dermatitis. The data obtained were compared to those obtained in healthy children. The stress-activating and stress-limiting systems were established to be activated in all the patients. It is concluded that the intensity of the adaptation compensatory process depends on the clinical form, disease standing, and spreading of skin impairment. PMID- 1866241 TI - [Various indices of collagen metabolism in children with rheumatoid arthritis]. AB - To study collagen metabolism, 113 children aged 3 to 14 years afflicted with rheumatoid arthritis and 43 conventionally normal children were examined. The patients were examined for free and protein-bound hydroxyproline in the blood serum and synovial fluid and for total hydroxyproline in diurnal urine. The blood serum and synovial fluid showed a decline of free and a rise of protein-bound hydroxyproline, more marked in severe rheumatoid arthritis, its higher activity and damage to numerous joints. Excretion of free and total hydroxyproline with urine was significantly lower than in the normal children whatever the form of rheumatoid arthritis, its activity or number of the joints involved into the process. In view of the lack of hydroxyprolinuria in the sick children, the authors discuss a hypothesis of a potential initial decrease of collagen formation in children afflicted with rheumatoid arthritis, suggesting its relationship to the "ligand pathology". PMID- 1866242 TI - [Adrenocortical function in children with connective tissue syndromes and funnel chest deformation]. AB - Measurement of the content of C-21-corticosteroids in the diurnal urine by thin layer chromatography has demonstrated that in children with isolated and syndromal forms of funnel-like chest deformation, grades II and III, adrenocortical function is decreased. In preschool children, such a decrease is accompanied by proneness to the tense biosynthesis of glucocorticoids. Children with congenital hereditary connective syndromes manifest adrenocortical dysfunction, most characteristic of Marfan's syndrome, and, to a less degree, of Ehlers-Danlos syndrome and unclassified complex of developmental defects with the Marfan-like phenotype. In view of this fact, the children with Marfan's, Ehlers Danlos syndromes and with the unclassified complex of developmental defects with the Marfan-like phenotype and children with funnel-like chest deformation, grades II and III, should be given glucocorticoid hormones in stressful conditions (severe diseases, traumas, operations). PMID- 1866243 TI - [Clinical importance of determination of lipid peroxidation of erythrocyte membrane in children with mucoviscidosis]. AB - The intensity of membranous red blood cell metabolism (lipid peroxidation /LPO/ and malonic dialdehyde /MDA/ metabolism) was examined in children suffering from mucoviscidosis depending on the gravity of the clinical manifestations of the disease. The membranopathological processes accompanied by different disorders of membranous metabolism, depending on the patient's status gravity and the intensity of inflammation in the respiratory organs were revealed. Based on the disagreement between different parameters that characterize LPO of red blood cells and MDA metabolism the conclusion is drawn that in children with mucoviscidosis, the metabolic processes occurring at the level of cellular membranes are not balanced. The data obtained point to the necessity of an individual approach to the use of membranoprotectors in multimodality treatment of children with mucoviscidosis together with the control over the treatment efficacy on the basis of a dynamic follow-up of membranous LPO with the aid of the method employed in the work. PMID- 1866244 TI - [Clinico-morphological comparison in children with infectious endocarditis]. AB - As many as 21 children suffering from infectious endocarditis (IE) were examined for the clinical and morphological picture of the disease. The patients' age ranged from 2 to 15 years. In 15 children, IE developed in association with different congenital diseases; in one patient, in the presence of rheumatic heart disease, and in 5 patients, in unaffected heart valves. The sectional material was examined in 19 cases whereas the operational material in 2 cases. Analysis of the data obtained has shown that early diagnosis of IE (primary and secondary) may not infrequently be fairly difficult, which is likely to result in the late administration of antibacterial therapy. In addition to the involvement of the valvular apparatus of the heart, the majority of the patients demonstrated the signs of focal myocarditis and postmyocarditic cardiosclerosis, which is one of the causes of the development of refractory heart insufficiency. IE children mostly die from heart insufficiency and thromboembolism. PMID- 1866245 TI - [Arterial bed of myocardium in congenital heart defects]. AB - Structural reconstruction of the myocardial arteries seen in congenital heart disease was analyzed and its importance for cardiac activity was defined on the basis of studying case reports, postmortem examinations and morphological data on 127 abnormally formed hearts. It has been established that developmental abnormalities of the heart may be accompanied by myocardial hypertrophy and lesions of the coronary arteries, having an adaptation and pathological character. The former ones lie in hypertrophy and hyperplasia of vascular wall muscles, whereas the latter ones in sclerosis and thrombosis of the arteries, thus creating prerequisites for heart decompensation. PMID- 1866246 TI - [Diagnosis of allergy to mold fungi in children with bronchial asthma]. AB - As many as 360 children with bronchial asthma were examined for fungal sensitization. In addition to intracutaneous tests, use was made of the natural leukocyte migration inhibition test and leukocyte lysis test under the action of a specific allergen. The data obtained attest to a high portion (23.3%) of fungal sensitization among children suffering from bronchial asthma in the BSSR, high specificity of the leukocyte migration inhibition test and leukocyte lysis in the diagnosis of fungal sensitization. PMID- 1866247 TI - [Ultrasonic methods in diagnosis of urinary tract defects in children during mass screening]. AB - Materials on urinary diseases collected by maternity hospitals and children's outpatient clinics and pertaining to 145,979 children of different ages including neonates were compared to the ultrasound data on 10,396 children of the same age. According to the ultrasound data, the incidence of urinary system abnormalities in children is 1.83 +/- 0.196%. The highest rate of the diseases was recorded in neonates. Later it was found to decrease. The method of ultrasound diagnosis can be used as a screening stage in mass prophylactic examinations of the childhood population of all ages including the earliest one. It is advisable that the method be introduced in medical practice of the city (regional) and interregional outpatient clinics. PMID- 1866248 TI - [Blood aggregation in duodenal ulcer]. AB - Thirty-six children with duodenal ulcer were examined for the coagulation and thrombocytic components of hemostasis. Use was made of the new coagulologic research methods based on administration of the synthetic tri- and tetrapeptides containing a chromoform group. The high sensitivity of the synthetic peptides enables the use of plasma in high dilutions, owing to which the effect of inhibitors is decreased and a small amount of blood is only required, being of paramount importance in carrying out serial tests. In acute ulcer 1/3 of the children show the signs of the DIC syndrome compensated at the expense of the high content of anticoagulants. At the same time 4 patients were discovered to have coagulologic disorders characteristic of Willebrand's disease (3 cases) and thrombasthenia (1 case). The coagulologic alterations should be taken into consideration in treatment administration, since the compensated DIC syndrome untreated by anticoagulant therapy aggravates the course of the ulcerous process and gives rise to hemorrhagic diathesis. Meanwhile in children with hemorrhagic diathesis, peptic ulcer may cause severe, life-threatening hemorrhages. PMID- 1866249 TI - [The importance of congenital enterovirus infection in perinatal pathology]. PMID- 1866250 TI - [Chronopharmacological approach to the treatment of children with bronchial asthma]. PMID- 1866251 TI - [Results of antirecurrence treatment of pyelonephritis in children]. PMID- 1866252 TI - Dignified in death. PMID- 1866254 TI - Blood rights. PMID- 1866253 TI - Hard-fought battle. PMID- 1866255 TI - Short-changed. PMID- 1866256 TI - Pay and conditions. The wages of trusts. PMID- 1866257 TI - Pay and conditions--divided states. PMID- 1866258 TI - Victorian values. PMID- 1866259 TI - Death of a hospital. PMID- 1866260 TI - Reducing hospital respiratory infections. PMID- 1866261 TI - Vibroacoustic stimuli and fetal behavior. PMID- 1866262 TI - Predictors of outcome for abstinent alcoholics. PMID- 1866263 TI - Education--devolving responsibility. PMID- 1866265 TI - Computing in practice. Information management and technology. Unfamiliar language? PMID- 1866264 TI - Midwifery--team labour. PMID- 1866266 TI - Medication education. PMID- 1866267 TI - Arts in action. Reviving memories. PMID- 1866268 TI - Diabetes. Agreeing on advice. PMID- 1866269 TI - Diabetes. Care of a gangrenous foot. PMID- 1866270 TI - Home help for people with HIV. PMID- 1866271 TI - HIV test no longer pre-empts life insurance automatically. PMID- 1866272 TI - The right to keep mum. PMID- 1866273 TI - Conduct unbecoming? PMID- 1866274 TI - Forgotten few. PMID- 1866275 TI - No easy option. PMID- 1866276 TI - Skin deep concern. PMID- 1866277 TI - Still crazy after all these years? PMID- 1866278 TI - Change in the ward. Making things happen. PMID- 1866279 TI - Change in the ward. A structured approach. PMID- 1866280 TI - Increasing knowledge. PMID- 1866281 TI - The view from the ward. PMID- 1866282 TI - Unstable lodgings. PMID- 1866283 TI - Sight restored. Care study. PMID- 1866284 TI - Return to nursing. Back to school. PMID- 1866285 TI - Return to nursing. Back to work. PMID- 1866286 TI - Placebo response in mild depression. PMID- 1866287 TI - Primary nursing. Philosophy for change. PMID- 1866288 TI - Primary nursing. A waste of energy? PMID- 1866289 TI - Primary nursing. North of the border. PMID- 1866291 TI - Someone to watch over me. PMID- 1866290 TI - Primary nursing. The Ulster experience. PMID- 1866292 TI - Under the spotlight. PMID- 1866293 TI - Exchanging ideas. PMID- 1866294 TI - Over the counter. PMID- 1866295 TI - Body politic--smoke-buster. PMID- 1866296 TI - Career patterns. The collapse of the conventional career. PMID- 1866297 TI - Career patterns. Equal to the task. PMID- 1866298 TI - Individual nurses must resolve to keep up their own personal campaign to ensure that patients with AIDS/HIV receive non-judgmental care and compassion. PMID- 1866299 TI - Career patterns. Different paths. PMID- 1866300 TI - Nursing overseas. After the killing fields. PMID- 1866301 TI - Self-care in the community. PMID- 1866302 TI - Transplanting fetal tissue. PMID- 1866303 TI - Plans for a better future. PMID- 1866304 TI - A fruitful collaboration. PMID- 1866305 TI - The impact of 12-hour nursing shifts. PMID- 1866306 TI - Nurses and the law. Making the law. PMID- 1866307 TI - Accountability: just between you and me. PMID- 1866309 TI - Child health--a taste of things to come. PMID- 1866308 TI - Child health--prepare for the best. PMID- 1866310 TI - Ignorant views on HIV revealed. PMID- 1866312 TI - Accuracy of self-measurement of body fat distribution by waist, hip, and thigh circumferences. AB - There are indications that body fat distribution, independent of obesity, may be a disease risk factor. The accuracy of self-measurement of waist, hip, and thigh circumferences, indicators of fat distribution, were examined for 227 women (aged 19-45) who were sent either a calibrated or uncalibrated tape measure and subsequently remeasured by a trained technician. Subjects tended to underestimate all circumferences somewhat. Spearman correlations between self-measurement and technician measurement were 0.88, 0.89, and 0.86 for the waist, hip, and thigh, respectively, and 0.65 and 0.77 for the waist-to-hip waist-to-thigh ratios. Correlations for waist, but not other measures, were better with the uncalibrated than with the calibrated tape. Accuracy did not vary within strata of education, body mass index, or waist-to-hip ratio. Subjects were able to measure their circumferences with reasonable accuracy. Circumference measures were more accurate than were computed ratios of circumferences; waist-to-thigh ratios were more accurate than were waist-to-hip ratios. PMID- 1866311 TI - Quantitative review of studies of dietary fat and rat colon carcinoma. AB - A quantitative overview of 14 studies of rat colon carcinogenesis was undertaken to examine the relationship between fat intake, and fat intake by degree of saturation, on the incidence of colon carcinoma while controlling for calorie consumption. Calorie consumption was not recorded in 11 of the 14 studies. Hence, two types of analyses were conducted. The first examines carcinoma incidence as a function of percent fat (by weight), with calories controlled for by including weight gain per week in the analysis. The second estimates calories per day, for studies not providing such information, using weight gain per week and age at death, followed by a joint analysis of estimated fat calories and estimated total calories. With either approach, a rather strong positive relationship between colon carcinoma incidence and fat intake is indicated for Fischer 344 rats, but no association is apparent for Sprague-Dawley rats. This situation is somewhat clarified when the degree of saturation is taken into account: both strains gave results that suggest a negative relationship between colon cancer incidence and omega-3 fatty acids intake and a positive relationship with non-omega-3 polyunsaturated fat intake among Fischer 344 rats. These analyses suggest an important and specific role for dietary fat in the promotion of rat colon carcinoma. PMID- 1866313 TI - Endogenous nitrosation of L-proline by dietary-derived nitrate. AB - Two studies were conducted to assess the availability of normal dietary sources of nitrate for endogenous nitrosation of an amino acid substrate, L-proline, and to investigate the potential for dietary ascorbic acid to inhibit such nitrosation. In the first study, 16 subjects consumed a salad meal (containing about 172 mg nitrate) with and without a loading dose of proline. A significant increase (10.8 compared with 2.7 micrograms/24 hrs, p less than 0.0001) in mean urinary N-nitrosoproline (NPRO) excretion following meal plus substrate ingestion was indicative of intragastric proline nitrosation by meal-derived nitrate. In the second study (19 different subjects), the mean urinary NPRO level was significantly decreased (15.8 micrograms compared with 28.4, p = 0.022) by inclusion of ascorbic acid sources in the meal. This demonstrated inhibition of proline nitrosation by dietary sources of the vitamin. Large interindividual variation in nitrosating ability was apparent that was associated with variation in meal nitrate to salivary nitrite conversion. Although meals containing fresh vegetables, as tested here, could provide sufficient nitrate to result in endogenous formation of N-nitroso compounds, there will be considerable inter- and intraindividual variation in the extent of this process. PMID- 1866315 TI - Effect of long-term treatment of two tobacco-specific N-nitrosamines on the vitamin A status of mice. AB - The effect of long-term treatment of two important tobacco-specific N nitrosamines, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl) 1-butanone (NNK), on the depot or circulating levels of vitamin A of Swiss and BALB/c male mice was studied. It was observed that treatment of both NNN and NNK in Swiss and BALB/c mice decreased liver vitamin A levels significantly. NNK treatment also caused a decrease in the levels of vitamin A in plasma. PMID- 1866314 TI - Associations between breast cancer, plasma triglycerides, and cholesterol. AB - A case-control study investigating the association between plasma lipids and breast cancer was conducted among women aged 30-80 in Buffalo, NY. All eligible women from a large breast clinic and two area physicians' offices were requested to participate over a one-year period. Subjects completed a health questionnaire and donated a fasting blood sample prior to diagnostic breast biopsies. The 83 women found to have breast cancer (cases) had significantly higher plasma triglyceride values than did the 113 women found not to have breast cancer (controls). Lower plasma beta-carotene values were associated with breast cancer, but only in those women with elevated triglyceride or cholesterol. Plasma cholesterol values were lower in those breast cancer cases presenting with more advanced stages of cancer, suggesting that metabolic effects of clinical and preclinical breast cancer may lower cholesterol levels. Although the limitations of case-control studies are well-recognized, these data suggest an etiologic role for plasma triglycerides and beta-carotene or for related dietary factors. PMID- 1866316 TI - Enhancing effect of ethanol or sake on methylazoxymethanol acetate-initiated large bowel carcinogenesis in ACI/N rats. AB - Effects of ethanol or sake on intestinal carcinogenesis by methylazoxymethanol (MAM) acetate were examined in two experiments. In the first experiment, 39 male ACI/N rats were given two weekly intraperitoneal injections of MAM acetate (25 mg/kg body wt) and divided into two groups, with Group 1 being given 10% ethanol and Group 2 being given distilled water. The incidence of colonic cancer in Group 1 (15/17, 88%) was higher than in Group 2 (9/16, 56%, p = 0.040). Differences in the incidences of rectosigmoidal colonic neoplasms were even more marked (59% vs. 19%, p = 0.019) and their proportion of the total number of large intestinal neoplasms was greater in Group 1 (36%) than in Group 2 (15%, p = 0.046). In the second experiment, 97 female ACI/N rats were divided into 6 groups, with the animals of Groups 1-5 being given MAM acetate (2 times, 25 mg/kg body wt). Rats in Group 6 received saline. The rats received isocaloric drinks: Group 1, sake; Group 2, 50% sake; Groups 3 and 6, 15% ethanol; Group 4, 7.5% ethanol; and Group 5, nonalcoholic water. Incidences of rectosigmoidal colonic neoplasms in Groups 1, 2, and 3 (53%, 46%, and 50%) tended to be higher than in Group 5 (38%). Their proportions of the total number of large intestinal neoplasms in Groups 1 (68%) and 2 (67%) were slightly greater than in Group 5 (45%). The results suggest an enhancing effect of ethanol or sake on rectosigmoidal colonic carcinogenesis. PMID- 1866318 TI - Vitamin C: biologic functions and relation to cancer. September 10-12, 1990, Bethesda, Maryland. Abstracts. PMID- 1866317 TI - Nutritional risk factors and ovarian cancer. AB - In a hospital-based case-control study, consumption of lactose-containing (dairy) foods and foods containing beta-carotene by 71 women with epithelial cancer of the ovary and 141 matched controls was investigated. No significant differences were found between cases and controls in the frequency of consumption of dairy foods or in the amount of lactose consumed. Consumption of carrots was found to decrease risk. Logistic regression analyses indicated a protective effect of high beta-carotene intake (odds ratio = 0.3, 95% confidence interval = 0.1-0.8), after adjusting for body mass, smoking, and lactose consumption. PMID- 1866319 TI - [Emergency endoscopic sphincterotomy in acute obstructive cholangitis]. AB - In 45 patients with acute obstructive cholangitis (AOC) endoscopic sphincterotomy (ES) was performed within 24 hours after admission. Criteria for the diagnosis of AOC were as follows: clinical symptoms consisting of fever and chills, right upper abdominal pain, and jaundice (Charcot's triad) with coexisting laboratory data as elevated WBC, ERS, bilirubin level and evidence of obstructive biliary disease confirmed by endoscopic retrograde cholangiopancreatography. The causes of AOC were: in 38 patients (84.5%)--common bile duct stones, in 2 patients (4.5%)--carcinoma of the papilla of Vater, and in 5 patients (11%)--benign stenosis of the papilla of Vater. A rapid clinical improvement was observed in 40 patients after ES. Within 24 hours after ES patients had relief of pain, fever subsided and white blood cell count returned from 11.7 +/- 6.9 G/l to 7.0 +/- 3.0 G/l. Bilirubin level decreased from 101 +/- 86 mumol/l to 77 +/- 68 mumol/l. Endoscopic drainage failed only in 4 patients (9%) who required surgery. One patient (2%)--died. In the treatment of acute obstructive cholangitis urgent endoscopic sphincterotomy should be a method of choice. Surgery should be reserved only for patients in whom ES failed. PMID- 1866320 TI - [Value of two-dimensional echocardiography in predicting the clinical course and fates of patients 2 years after myocardial infarction]. AB - 133 patients with acute myocardial infarction, admitted to hospital 24 hours or less from the beginning of chest pain were investigated. Two-dimensional echocardiography (ECHO 2D) was performed 1-2, 3-5, 7-10, 21-28 days and 3, 6, 9, 12, 18 and 24 months after myocardial infarction. Relations between ECHO parameters, clinical course and prognosis. 2 years after myocardial infarction were analysed. Worse clinical course and prognosis during 2 years after myocardial infarction predict high values of 1) asynergy index (greater than or equal to 1), 2) percentage of asynergy segments (greater than or equal to 50) and 3) percentage of left ventricular (LV) akinetic and (or) dyskinetic segments (greater than or equal to 37.5). Right ventricular asynergy and maintenance or increase of LV asynergy degree aggravate clinical course and prognosis too. PMID- 1866321 TI - [Dynamics of disorders of ventricular contraction studied by two-dimensional echocardiography 2 years after myocardial infarction]. AB - Two-dimensional echocardiography (ECHO 2D) was performed in 133 patients 1-2, 3 5, 7-10, 21-28 days and 3, 6, 9, 12, 18 and 24 months after myocardial infarction. During 2-years observation after myocardial infarction a gradually diminishing occurrence of left ventricular (LV) systolic wall motion abnormalities, is seen mostly--akinesia. Dyskinesia is the most persistent form of asynergy appearing with similar frequency during the whole study period. Improvement, worsening or no changes of LV asynergy are found with similar frequency in hospital phase. Favourable asynergy changes predominantly++ in the ambulatory phase. Right ventricular (RV) asynergy is found rarely (5%) in transmural inferior infarction only. It coexists with enlargement of RV. RV asynergy is always associated with LV asynergy, mostly of its inferior or posterior wall. PMID- 1866322 TI - [Megakaryocytopoiesis in different blood diseases. II]. PMID- 1866323 TI - [Transplantation of the kidney with preoperatively undetected clear cell carcinoma]. PMID- 1866324 TI - [Iatrogenic disease and inappropriate physician-patient relations as the causes of rejecting scientific medicine]. PMID- 1866325 TI - [Diagnostic effectiveness of Rtg-TV, echocardiography and computerized tomography in mitral valve calcinosis]. AB - The aim of the study was a comparative evaluation of the three diagnostic procedures: fluoroscopy (Rtg-TV), echocardiography (ECHO) and computer assisted tomography (CT) in detection of mitral valve calcifications. These methods were applied to the 46 patients with mitral valve disease (24 males and 22 females which age was 24-56 years). The results were compared with radiograms of isolated valves after surgery. We found that the most efficient diagnostic method is CT which provided following results: sensitivity--100%, specificity-- 89% efficiency -95%, false positives and false negatives rates 11% and 0% respectively. The same diagnostic indices in the other methods were: ECHO--92%, 77%, 85%, 22%, 7%; Rtg TV--50%, 100%, 75%, 0%, 50%. The last method can not be used as a routine examination in detecting of the mitral valve calcifications because of its low sensitivity+ and high grade of false-negatives rate. PMID- 1866326 TI - Multiple coronary stenoses of unknown etiology. AB - The case of a 13-year-old girl with multiple coronary stenoses and abundant collaterals, but no risk factors, is described. She was not suspected of having ischemic heart disease until an abnormal electrocardiographic pattern was detected during a routine examination in school. All children with electrocardiographic abnormality should be carefully examined, even though they have neither symptoms nor coronary risk factors. PMID- 1866327 TI - Bull-worker syncope: congenital subclavian steal syndrome following isometric exercise. AB - A patient with congenital great artery abnormality facilitating subclavian steal is presented. Sustained isometric upper body exercise, using a "Bull-Worker," resulted in vertebrobasilar steal symptoms (subclavian steal syndrome) shortly after exercise. A mechanism for the timing of symptoms following isometric exercise is suggested. PMID- 1866328 TI - Cerebral arteriovenous malformation diagnosis by two-dimensional color-coded Doppler ultrasonography of the head. AB - Two-dimensional color-coded Doppler examination revealed a cranial arteriovenous (AV) malformation in a critically ill newborn with intractable congestive heart failure. This case emphasizes the value of color-coded Doppler in the diagnosis of this rare malformation. PMID- 1866329 TI - Multiple floppy valves with all cardiac valves prolapsing: clinical course and treatment. AB - Two cases with prolapse of all four cardiac valves are described and compared with two similar ones previously reported. The severity and progression of regurgitation of each of the valves differed by case, despite having similar echocardiographic findings consistent with the diagnosis of multiple floppy valves. Two of the four patients had their aortic valve replaced because of severe regurgitation: the excised valves revealed myxomatous degeneration. None of the patients had any stigmata of Marfan or Ehlers-Danlos syndrome, except for the presence of hyperextensive joints. There may be an unknown collagen disorder that caused floppiness in all the valves. PMID- 1866330 TI - Aplasia of semilunar valve leaflets: two case reports and developmental aspects. AB - Two fetuses of approximately 11 weeks development with aplasia of the pulmonary as well as the aortic valve leaflets are reported. Both cases showed additional cardiac malformations. Case 1, with all leaflets missing, also had double-outlet right ventricle, hypoplastic left ventricle, large ventricular septal defect, straddling tricuspid valve, and atretic mitral valve. Case 2, with only one hypoplastic aortic valve leaflet, showed hypoplasia of the mitral valve and the left ventricle, and a subaortic ventricular septal defect. The observations made and data in the literature suggest that aplasia of semilunar valve leaflets reflects an underdevelopment of the endocardial cushion swellings at the ventriculoarterial junction, rather than resulting primarily from a malseptation of the cardiac outflow tract. PMID- 1866331 TI - Cardiac fibroma presenting with clinically significant arrhythmias in infancy. AB - Supraventricular or ventricular ectopy has been reported in association with cardiac fibroma. We report two patients, one with acquired complete heart block and one with mixed ventricular and supraventricular arrhythmias associated with this rare tumor of the heart. PMID- 1866332 TI - Hypoplastic left heart syndrome with rhabdomyoma of the left ventricle. AB - A case of primary cardiac tumor with hypoplastic left heart syndrome (HLH) is presented. Sonographic examination at 32 weeks' gestation revealed a large tumor in the left ventricle of the fetal heart. The newborn died of congestive heart failure at 11 days of age. Autopsy demonstrated a large tumor in the left ventricle obliterating most of the left ventricular cavity, aortic atresia, and hypoplastic ascending aorta. Microscopically, the cardiac tumor showed "spider cells" characteristics of rhabdomyoma. PMID- 1866333 TI - Unique variant of Taussig-Bing heart: double-outlet right ventricle with double ventricular septal defects and double overriding of great arteries. AB - A cyanotic, tachypneic newborn was diagnosed to have double-outlet right ventricle of the Taussig-Bing type. Cardiac failure did not respond to medical treatment or surgical palliation. Postmortem examination revealed two ventricular septal defects (VSDs), one a malalignment VSD in the membranous septum and adjacent tissue and the other in the anterosuperior part of the muscular septum. The D-malposed aortic root emerged mainly from the right ventricle, with aortic mitral continuity. The larger posterolateral pulmonary root arose almost entirely from the right ventricle, confluent with the muscular VSD, and unrelated to the mitral valve. Its right ventricular aspect was obstructed by hypertrophied infundibulum. This unique malformation of the heart functioned as a double-outlet right ventricle of Taussig-Bing type. In addition, however, the malformation had elements of tetralogy of Fallot because of the malaligned VSD and hypertrophied conal musculature (although pulmonary flow was excessive), and also of complete transposition of the great arteries because of the arrangements of the two VSDs, which favored aortic flow from right ventricle and pulmonary blood flow from the left ventricle. Thus, a single heart presented similarities to three anatomic and functional entities. PMID- 1866334 TI - Discordant atrioventricular connection and concordant ventriculoarterial connection in situs inversus: isolated ventricular noninversion. AB - A case of discordant atrioventricular (AV) connection and concordant ventriculoarterial (VA) connection (with aortomitral fibrous continuity and tricuspid pulmonary discontinuity) in situs inversus (I, D, I) is reported because of its rarity. This segmental combination with abnormally related great arteries in the absence of anomalies of venous connections and/or splenic anomalies is extremely rare. PMID- 1866335 TI - Truncus arteriosus associated with mitral atresia and a hypoplastic left ventricle. AB - The association of truncus arteriosus with congenital left heart abnormalities is rare. We describe a case of truncus arteriosus associated with mitral atresia and a hypoplastic left ventricle. In 11 other patients diagnosed with truncus arteriosus, none had left heart hypoplasia. Despite the truncal root being primarily or entirely committed to the right ventricle, more right than left heart abnormalities have been found. This is in contrast to double-outlet right ventricle in which left heart abnormalities are more often associated. PMID- 1866336 TI - Fetal atrial flutter and necrotizing enterocolitis in a term neonate. PMID- 1866337 TI - An alternative approach to difficult mitral valve problems. PMID- 1866338 TI - Atrioventricular block in the neonate. PMID- 1866339 TI - 18p monosomy syndrome. PMID- 1866340 TI - Reduced left ventricular afterload and increased contractility in children with insulin-dependent diabetes mellitus: an M-mode and Doppler-echocardiographic evaluation of left ventricular diastolic and systolic function. AB - Twenty-three children with diabetes mellitus, their ages ranging from 0.2-9.8 years, but with no sign of diabetic microvascular disease were investigated by M mode and Doppler echocardiography, along with a comparable group of control subjects. In the diabetics, the fractional shortening and the mean velocity of fractional shortening were 14 and 18% higher, respectively, whereas the left ventricular end-systolic wall stress, an indicator of left ventricular afterload, was markedly reduced (22%). Assuming an unchanged preload in the two groups, this indicates a reduced afterload in these children. Systolic and diastolic time intervals, heart rate, and blood pressure were similar in diabetics and controls. Doppler-derived transmitral left ventricular filling indices were also similar. Thus, in these diabetic children no signs of left ventricular diastolic abnormality were detected. The state of hypercontractility of the left ventricle is considered to be due to a reduced afterload in early insulin-dependent diabetes. PMID- 1866341 TI - Variations in local PGE levels: a potential factor in therapeutic responsiveness? AB - It was hypothesized that it is the concentration of PGE in the plasma which actually reaches the ductus arteriosus which determines ductal response to PGE administration. Therefore, site specific PGE levels were studied in two infants with ductus dependent congenital heart lesions who were receiving PGE1 infusions. PGE levels were found to vary in a fashion related to the infusion site and the specific cardiac anatomy and hemodynamics of each patient. One of our patients, for instance, had a double outlet right ventricle with high pulmonary vascular resistance and right to left ductal shunting. This infant was given an intraarterial infusion of PGE. The plasma concentrations of PGE in the ductal blood of the infant were negligible. Assuming that ductal site specific PGE levels are critical in mediating the therapeutic response, hemodynamics and infusion site are factors that should be considered when initiating a PGE infusion, or in evaluating a therapeutic failure of PGE. PMID- 1866342 TI - Asymptomatic myocardial infarction in Kawasaki disease: long-term prognosis. AB - Eight patients with Kawasaki disease who had sustained asymptomatic myocardial infarction 8-15 years ago (mean, 13.1 years) were reexamined by various noninvasive cardiac function tests to assess long-term prognosis. At present, electrocardiograms (ECGs) are normal in six patients. However, all eight patients had a prolonged preejection period (PEP) to left ventricular ejection time (LVET) ratio 30 s after amylnitrate (AN) inhalation. Six patients had perfusion defects by exercise thallium-201 myocardial scintigraphy, and two patients developed ST segment depression in treadmill exercise testing. These patients are symptom-free even though their physical activity has not been restricted. Yet they proved to have serious abnormalities suggesting sequelae of myocardial infarction or existing myocardial ischemia. Judging from the results of noninvasive cardiac function tests and recently performed coronary angiography, five of the eight patients require coronary bypass surgery. PMID- 1866343 TI - Cardiac arrhythmias after surgical correction of total anomalous pulmonary venous connection: late follow-up. AB - Sixteen patients (10 males and six females) aged 7 months to 20 years, who had undergone surgical repair in the first year of life for total anomalous pulmonary venous connection (TAPVC), underwent assessment of cardiac rhythm by 24-h electrocardiogram (ECG) monitoring, nine of them also had maximal exercise treadmill tests, 3 months to 19.5 years after surgical repair. No patient had symptoms of an arrhythmia and the resting ECG was normal in all except one who had occasional single supraventricular ectopic beats. But on 24-h ECG monitoring significant arrhythmias were recorded in six of the 16 patients, including supraventricular tachycardia (three patients), bradyarrhythmia (two patients), sick sinus syndrome (two patients), and multiform supraventricular and ventricular ectopic beats (two patients). Five of these six patients were assessed more than 6 years after surgery. An inappropriate chronotropic response was seen on maximal exercise treadmill testing in four patients; three of them had arrhythmias previously recorded by 24-h ECG monitoring. Our observations show that significant arrhythmias may occur in asymptomatic patients long after TAPVC correction, and we therefore recommend long-term follow-up of these patients, even if they are asymptomatic. PMID- 1866345 TI - Preparing general orthopedists for foot and ankle care. PMID- 1866344 TI - Cardiac output by Doppler echocardiography in the premature baboon: comparison with radiolabeled microspheres. AB - Pulsed-Doppler echocardiography (PDE) is a useful noninvasive method for determining left ventricular output (LVO). However, despite increasingly widespread use in neonatal intensive care units, validation studies in prematures with cardiopulmonary disease are lacking. The purpose of this study was to compare radiolabeled microsphere (RLM) and PDE measurements of LVO, using the critically ill premature baboon as a model of the human neonate. Twenty-two paired RLM and PDE measurements of LVO were obtained in 14 animals between 3 and 24 h of age. Average PDE LVO was 152 ml/min/kg (range, 40-258 ml/min/kg) compared to 158 ml/min/kg (range, 67-278 ml/min/kg) measured by RLM. Linear regression analysis of the paired measurements showed good correlation with a slope near unity (gamma = 0.94x + 4.20, r = 0.91, SEE = 25.7 ml). We conclude that PDE determinations of LVO compare well with those measured by RLM in the premature baboon. PDE appears to provide a valid estimate of LVO and should be useful in human prematures with cardiopulmonary distress. PMID- 1866346 TI - Lower extremity torsional deformities in children: a prospective comparison of two treatment modalities. AB - A prospective randomized analysis was conducted on children with lower extremity torsional deformities. Its purpose was to define the natural history of these anomalies and to determine the efficacy of treatment with a Denis-Browne splint. The natural history of pediatric lower extremity torsional deformities is to correct toward the mean of the population. The Denis-Browne splint did not alter the natural history of lower extremity torsional deformities as defined by the foot progression angle. PMID- 1866347 TI - Girdlestone's modified resection arthroplasty. AB - Thirty-three patients were operated for septic (n = 20) and aseptic (n = 13) loosening of their hip prostheses using Girdlestone's operation over 10 years. An average of 46.6 months later, 22 of these patients were given a follow-up examination. Clinical evaluation according to Harris showed an improvement in mean values from 25 to 53 points, which can be attributed mainly to a marked reduction in pain, as function remained poor and the patients still depended on walking aids. The infection ceased in 92% of the patients with septic prosthesis loosening. PMID- 1866348 TI - Surgical treatment for primary interdigital neuroma. AB - We studied 366 feet in 313 patients who underwent surgical treatment for a primary interdigital neuroma through a dorsal web-splitting incision. Three hundred five feet in 259 patients were available for follow up, which averaged 5.9 years (range: 2.8 to 13); 45.2% of these patients were completely satisfied, 33.8% were satisfied with minor reservations, 9.2% were satisfied with major reservations, and 11.8% were dissatisfied after the surgical procedure. Patient satisfaction was directly related to the size of the neuroma found at the time of operation. Bilateral procedures were associated with a higher rate of dissatisfaction. The third web space accounted for 91% of the neuromas. PMID- 1866349 TI - Anatomic variations of the blood supply of the soleus muscle. AB - A total of 36 cadaver and fresh amputation specimens were studied by dissection. Two vascular patterns were identified--a segmental posterior tibial artery (Type 1) and a proximally dominant posterior tibial artery (Type 2). Type 1 was seen in 77.8% of cases, and Type 2 in 22.2%. Injection studies in five fresh specimens demonstrated numerous cross-connections between the two halves of the muscle. A distally based hemisoleus flap should not be performed when a Type 2 vascular pattern is encountered. Also, vascular cross-connections between the two halves of the soleus muscle should be preserved, when possible. PMID- 1866350 TI - Operative management of acute PCL injuries with associated pathology: long-term results. AB - Eighteen consecutive patients with posterior cruciate ligament injury and associated pathology were reviewed. All were re-examined with an average follow up of 5.4 years (range: 3.5 to 7.5). Six posterior cruciate ligaments were repaired to the femur with multiple #2 nonabsorbable suture, and one "mop end" mid-substance tear was repaired with sutures in each stump. Seven mid-substance tears were repaired and augmented with the semitendinosus tendon, while four additional mid-substance tears were repaired and augmented with the semitendinosus tendon and a Dacron stent (Meadox). One medial meniscus was repaired and one was partially excised, and one lateral meniscus tear was partially excised. The anterior cruciate ligament was repaired to the tibia in two knees, left alone (interstitial tear) in two, and excised with extraarticular iliotibial band tenodesis augmentation in five. At follow up, arthrometer readings (Stryker) correlated well with clinical examination. The four knees with Dacron stent had a 0 to 1 mm difference at 90 degrees, while the failures had greater than 5 to 6 mm. Six of these were in the repair alone group and two were in the repair with semitendinosus augmentation group. Eight knees (44.5%) had radiographic changes primarily in the medial compartment. Using Hughston's perimeters to evaluate the results, objective 55.5% were rated good, 27.8% were rated fair, and 16.7% were rated poor or failures. Using Clancy's criteria, 22.2% were excellent, 22.2% were good, 44.5% were fair, and 11.1% were rated failures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866351 TI - Displaced fractures of the head and neck of the radius in children: open reduction and temporary transarticular internal fixation. AB - This report reviews the results of 36 children surgically treated for fractures of the head and neck of the radius. Indications for operation were: displacement over 2 mm and/or angulation over 45 degrees. Treatment included open reduction and temporary internal fixation with a K-wire transfixing the joint. Eighteen children had a good result, 8 had a fair result, and 10 had a poor result. It appears that when radial head fractures are associated with severe displacement, a high rate of fair and poor results can be expected, despite treatment by open reduction and temporary internal fixation. PMID- 1866352 TI - Osteonecrosis of the knee detected only by magnetic resonance imaging. PMID- 1866353 TI - Acute hematogenous epiphyseal osteomyelitis. PMID- 1866354 TI - Recurrent elbow dislocations in a patient with Ehlers-Danlos syndrome. PMID- 1866355 TI - Seal finger. PMID- 1866356 TI - Ipsilateral proximal metaphyseal and flexion supracondylar humerus fractures with an associated olecranon avulsion fracture. AB - An ipsilateral proximal humerus fracture, "flexion" supracondylar humerus fracture, and olecranon fracture found together is a rare event. The supracondylar fracture should be reduced and percutaneously pinned before the ipsilateral upper extremity fractures are reduced. Displaced supracondylar fractures should be pinned with crossed smooth pins. Most pediatric proximal humerus and olecranon fractures can be treated closed. PMID- 1866357 TI - Meniscal salvage: maintenance of function. PMID- 1866358 TI - Radiologic case study. Blastomycotic osteomyelitis. PMID- 1866360 TI - Foreign-body pulmonary embolism. AB - The minimal incidence of pulmonary foreign-body embolism in a general pediatric pathology experience was ascertained by reviewing autopsy records, and the true incidence of pulmonary foreign-body embolism was determined by studying lung sections from 64 autopsies of patients who had undergone cardiac procedures. Seventeen cases of embolism were reported from 370 autopsies, an incidence of 4.6%. The true incidence of pulmonary foreign-body embolism was found to be 21.9% in the cardiac surgical autopsies and the minimal incidence was 5.1% in patients who had other types of surgery. No patients other than those having surgical procedures had embolism. Hair was found to be the embolic material in 35% of cases. Embolic lesions were characterized, staged, and correlated with clinical data. The pathogenesis of this condition is unclear, but it probably involves contamination of surgical materials with particulate matter. PMID- 1866359 TI - Postmortem recognition of fatty acid oxidation disorders. AB - With an appropriate protocol for collection, storage, and sample analysis, it should be possible to ensure correct diagnosis of disorders of fatty acid oxidation presenting to the pathologist. Appropriate counseling of affected families will lead to presymptomatic sibling diagnosis of these frequently treatable disorders, which, in turn, can prevent the catastrophic metabolic consequences of the disorders. PMID- 1866361 TI - Exogenous iron overload in perinatal hemochromatosis: a case report. AB - We report an infant with fatal neonatal liver disease in whom efforts to correct an associated unremitting anemia resulted in massive exogenous iron overload that was expressed as perinatal hemochromatosis (PH). Levels of iron and copper were elevated in multiple tissues. Echovirus subtype 9, recovered from the urine at age 3 weeks, may have been etiologic in the liver failure. PH is best viewed as a definable phenotype with an undefined genetic and/or environmental basis that emerges only in the context of severe perinatal liver disease. The absence of hemosiderin in splenic and bone marrow reticuloendothelial (RE) cells of our patient suggests an important role for RE cell dysfunction. PMID- 1866362 TI - Apoptosis: a basic pathological reaction of injured neonatal muscle. AB - A light and electron microscopic study of immature muscle cell degeneration induced by bupivacaine (BPVC) was performed. The pattern of muscle cell death is related to muscle maturity; in newborn rats, cell death has the morphology of apoptosis, whereas in the older animals muscle cell death resembles cell necrosis and the ultrastructural feature of these changes are essentially the same as those described in adult muscle. The ability to undergo apoptosis in response to a pathological stimulus is a common effector mechanism of immature muscle. PMID- 1866363 TI - Thymic involution with loss of Hassall's corpuscles mimicking thymic dysplasia in a child with transfusion-associated graft-versus-host disease. AB - A 7-year-old leukemic girl developed pancytopenia following chemotherapy and was given several transfusions of nonirradiated blood. Within 2 weeks she developed a maculopapular rash, fever, abnormal liver function, diarrhea, and wasting. She became septic and died 6 weeks later. Transfusion-associated graft-versus-host disease (GVHD) was suspected clinically. At autopsy, changes diagnostic of GVHD were present in the skin and liver. The remarkable feature of the case was the histopathology of the thymus, which was morphologically "dysplastic," i.e., minute, lymphoid depleted, devoid of a corticomedullary demarcation, and completely lacking in Hassall's corpuscles. These changes were virtually identical to those seen in the thymus of children with severe combined immunodeficiency disease (SCID). There was no evidence of preexisting immune deficiency. There is compelling experimental evidence that GVHD can produce changes in the thymus that are identical to those of "thymic dysplasia." These observations have led to the hypothesis that immunodeficiency associated with GVHD may stem, in part, from injury to thymic epithelium resulting in defective T cell maturation. As a corollary of this hypothesis, it has been suggested that the pathogenesis of some forms of SCID may involve GVHD-associated injury to the thymus by a maternal allograft acquired in utero. This report further documents thymic pathology in human GVHD and discusses these changes in the light of these ideas. PMID- 1866364 TI - Intraoral plexiform (multinodular) neurilemoma. AB - An intraoral (buccal) mass in a 6-year-old child was found to be a benign plexiform (multinodular) neurilemoma by fine-needle aspiration (FNA) biopsy cytology and histologic examination of the excised specimen. Clinical and pathological features of these rare tumors are reviewed, and the capacity of FNA to guide surgical planning in the pediatric population is emphasized. PMID- 1866365 TI - Two cases of fetal akinesia/hypokinesia sequence. AB - Two cases of fetal akinesia sequence are described. Both showed facial anomalies, arthrogryposis multiplex, bilateral camptodactyly, and pulmonary hypoplasia. One child had degeneration of large motor neurons of the thoracolumbosacral spinal cord and irregular atrophy of diaphragm; the other had left microphthalmia, hemiatrophy of the left temporal lobe with calcification of degenerated neurons, and hypoplasia of the cervothoracic spinal cord with decrease and degeneration of neurons. The iliopsoas and intercostal muscles showed focal myofiber atrophy. These findings suggested that some instances of this fetal akinesia syndrome might be due to neuromuscular dysfunction that occurred in utero and may have various causes. PMID- 1866366 TI - Nodular regenerative hyperplasia of fetal liver: a report of two cases. AB - Nodular regenerative hyperplasia in the liver is characterized by diffuse nodularity of the organ secondary to regenerative hepatocellular activity. This alteration is rare in infants and children. We present two cases of nodular regenerative hyperplasia found in fetuses that exhibited several other malformations, sirenomelia and features of schisis association in one and Poland's sequence in the other. PMID- 1866367 TI - Stereoselectivity in pharmacokinetics: a general theory. AB - Stereoselectivity in pharmacokinetics may be characterized by a measurable difference between enantiomers in a pharmacokinetic parameter. We propose that pharmacokinetic parameters may be classified according to three levels of organization in the body and that the hybrid character of parameters increases with the level of organization that they represent. At the molecular level are intrinsic metabolite formation clearances and fraction of drug unbound in plasma, reflecting the selectivity of an endogenous macromolecule for the enantiomers of a chiral drug molecule. At the organ level, pharmacokinetic parameters represent the combined effects of stereoselectivity in each of their component parameters within an organ. As a result, these parameters are of intermediate hybrid character. Parameters with the highest degree of hybrid character describe the pharmacokinetic behavior of a drug in the whole body. The stereoselectivity associated with each of the component parameters could either amplify or dampen the resultant stereoselectivity in hybrid parameters. The hypothesis that kinetic differences between enantiomers are inversely correlated with the degree of hybrid character was examined for four drugs: warfarin, verapamil, mephenytoin, and propranolol. By classifying pharmacokinetic parameters according to both the level of organization that they characterize and their hybrid nature, it becomes possible to account for stereoselectivity in drug distribution and elimination. PMID- 1866368 TI - Comparison of the methods for determining cell-surface and intracellular receptors for epidermal growth factor in the rat liver. AB - We compared methods for determining the distribution of epidermal growth factor (EGF) receptors between the cell surface and the cell interior in the rat liver. Incubation of isolated hepatocytes with 100 nM EGF for 20 min at 37 degrees C remarkably decreased the cell-surface EGF receptor density (internalization of receptors). The detergent Brij 35 was previously reported to permit assay of the intracellular latent EGF receptors in liver homogenates, but in the present investigation, Brij 35 lowered the affinity of EGF for the receptor depending on the detergent concentration, and the appearance of latent receptors was not observed. In contrast, permeabilization of the cells with digitonin, followed by an acid-washing procedure, increased the EGF binding capacity to close to the control level. Hence, the EGF receptors, internalized together with EGF molecules, were not degraded for at least 20 min, and the digitonin method is suitable for quantifying the intracellular EGF receptors. The binding capacities of the digitonin-treated and untreated control cells showed no difference upon digitonin treatment, suggesting that the bulk of EGF receptors exists on the cell surface. Further, cell-surface EGF receptor density was determined after the i.v. administration of EGF (300 micrograms/kg) to rats. Isolated hepatocytes prepared 30 min after the administration of EGF showed little binding for EGF on the cell surface, while the cell-surface EGF receptor density recovered to close to control values in cells prepared after 3 hr. PMID- 1866370 TI - Nonisothermal stability assessment of stable pharmaceuticals: testing of a clindamycin phosphate formulation. AB - The stability of an antibiotic formulation (clindamycin phosphate in dextrose), which is stable at room temperature, was assessed by nonisothermal kinetic analysis at elevated temperatures. A preliminary study, conducted to establish apparent rate order, verified the appropriateness of a first-order kinetic model. The test formulation was then heated linearly from 70 to 90 degrees C over 12 hr. Data (drug concentration, temperature, and time) were fitted to the first-order model using nonlinear least-squares regression. Arrhenius parameter estimates obtained from three nonisothermal trials, and rate constants at 25 degrees C derived by extrapolation, demonstrated acceptable reproducibility and were in agreement with values derived from isothermal experiments at 30, 45, 55, 65, and 75 degrees C. First-order rate constants obtained from studies conducted for 20 months at 25 degrees C were in accord with isothermal and nonisothermal results. PMID- 1866369 TI - Effect of receptor up-regulation on insulin pharmacokinetics in streptozotocin treated diabetic rats. AB - The present study investigated the mechanism by which the disposition of insulin is altered in streptozotocin (STZ)-treated diabetic rats as compared with 48-hr fasted normal (control) rats. It was shown by an indocyanine green infusion method that the hepatic plasma flow rate (QH) in diabetic rats (1.64 ml/min/g liver) is significantly higher than that in control rats (0.982 ml/min/g liver). The portal injection technique revealed that the unidirectional clearance (CLon), which represents the binding of A14-125I-insulin to surface receptors in the liver, is significantly elevated in diabetic rats, suggesting an increase in the surface receptor number (RT), i.e., up-regulation in the liver. In both control and diabetic rats, the total-body clearance (CLtot) and steady-state volume of distribution (Vdss) of labeled insulin decreased significantly with a simultaneous injection of unlabeled insulin (8 U/kg), confirming that the disposition of insulin is affected largely by specific, saturable receptor mediated processes. The CLtot and Vdss increased significantly in diabetic rats, while nonspecific portions of these parameters were not changed. From the increases in CLtot (80%) and QH (67%) in diabetic rats, a pharmacokinetic analysis has revealed a 40% increase in the hepatic intrinsic clearance (CLint,sp) of A14-125I-insulin via a specific mechanism in diabetic rats. In conclusion, we have provided in vivo evidence for a small increase in CLint,sp of insulin in STZ-diabetic rats compared with control rats, which may be caused by an increase in the surface receptor number in the livers of diabetic rats. PMID- 1866371 TI - A novel, self-correcting membrane coating technique. AB - A novel coating process, leading to formation of uniform, defect-free coating on solid dosage forms, is proposed. The coating process, termed "diffusion controlled interfacial complexation," involves a chemical reaction between a reactant incorporated in the solid unit to be coated and a polymer solution, forming the coating medium. The reaction results in the formation of an insoluble reactant-polymer film around the solid. The rate of film/membrane formation is controlled by the rate of diffusion of reactant through the reactant-polymer film. In the model system, calcium acetate was selected as the reactant and algin as the polymer. The coating process was mathematically characterized in terms of rate of increase in film thickness, film weight, and depletion of reactant. Compressed tablets coated using the above process provided zero-order release in distilled water. PMID- 1866372 TI - Absorption enhancing effect of cyclodextrins on intranasally administered insulin in rats. AB - The absorption enhancing effect of alpha-, beta-, and gamma-cyclodextrin (CD), dimethyl-beta-cyclodextrin (DM beta CD), and hydroxypropyl-beta-cyclodextrin (HP beta CD) on intranasally administered insulin was investigated in rats. Coadministration of 5% (w/v) DM beta CD to the insulin solution resulted in a high bioavailability, 108.9 +/- 36.4% (mean +/- SD, n = 6), compared to i.v. administration, and a strong decrease in blood glucose levels, to 25% of their initial values. Coadministration of 5% alpha-CD gave rise to an insulin bioavailability of 27.7 +/- 11.5% (mean +/- SD, n = 6) and a decrease in blood glucose to 50% of its initial value. The rate of insulin absorption and the concomitant hypoglycemic response were delayed for the alpha-CD-containing solution as compared to the DM beta CD preparation. The other CDs, HP beta CD (5%), beta-CD (1.8%), and gamma-CD (5%), did not have significant effects on nasal insulin absorption. DM beta CD at a concentration of 5% (w/v) induces ciliostasis as measured on chicken embryo tracheal tissue in vitro, but this effect is reversible. In conclusion, DM beta CD is a potent enhancer of nasal insulin absorption in rats. PMID- 1866373 TI - Structural requirements for the intestinal mucosal-cell peptide transporter: the need for N-terminal alpha-amino group. AB - The requirement for a free alpha-amino group for the intestinal peptide carrier mediated transport was investigated. A series of dipeptide analogues without the N-terminal alpha-amino group [including phenylpropionylproline, phenylacetylproline, N-benzoylproline, phenylacetyl-alpha-methyldopa, and hippuric acid (N-benzoylglycine)] were studied in the perfused rat intestinal segment. The absorption of phenylpropionylproline, phenylacetyl-alpha-methyldopa, and N-benzoylproline was concentration dependent. The transport parameters (mean +/- SD) of phenylpropionylproline and N-benzoylproline were as follows: Jmax*, 0.037 (+/- 0.019) mM; Km, 0.045 (+/- 0.027) mM; Pc*, 0.830 (+/- 0.130); and Pm*, 0.673 +/- 0.049; and Jmax*, 1.34 (+/- 0.24) mM; Km, 1.31 (+/- 0.30) mM; Pc*, 1.02 (+/- 0.11); and Pm*, 0; respectively. The intestinal permeabilities of phenylpropionylproline, phenylacetylproline, N-benzoylproline, and hippuric acid (N-benzoylglycine) were significantly reduced by dipeptides and cephradine. These results strongly suggest that these dipeptide analogues, without an alpha-amino group, are transported by the peptide carrier and provide more direct evidence that a free alpha-amino group is not absolutely essential for the mucosal-cell peptide carrier-mediated transport. PMID- 1866374 TI - Use of modified ethylcellulose lattices for microporous coating of osmotic tablets. AB - Commercially available lattices are often used to coat nonpareils or beads. Drug release occurs via diffusion through the polymer coating. Adequate release rates may be achieved with small particles because the surface area is large. However, tablets coated with unmodified lattices have exceedingly slow release rates. Therefore, a pore-forming agent, urea, was added to a commercially available ethyl cellulose latex, Aquacoat, to increase the release rate of drugs from coated osmotic tablets. Modified lattices were used to coat KCl and diltiazem.HCl tablets. Release of KCl and diltiazem into water or buffer solutions was determined in a standard U.S.P. dissolution apparatus. Rates varying from 1 to 100% release in 12 hr were obtained by varying the coating thickness, pore-former level, and plasticizer type and concentration. Scanning electron microscopy (SEM) showed that the urea was eluted from the coat in aqueous solution leaving a porous coating. Coat burst strengths were dependent on the coat thickness and the concentrations of pore former and plasticizer. Hence, modified lattices hold potential for use as coatings for controlled release osmotic formulations. PMID- 1866375 TI - Bioavailability of flurbiprofen following buccal administration. AB - The buccal absorption of flurbiprofen was evaluated in nine normal volunteers. Twenty milliliters of 2.5 mg/ml flurbiprofen solution (pH 8.03) was administered as a 1-min mouthwash or a 5-min mouthwash or swallowed. Serum was harvested from blood samples taken at specified times over a 12-hr period. Serum flurbiprofen concentration data indicate that the extent, but not the rate, of drug absorption was dependent upon the time of exposure of the flurbiprofen solution to the buccal membrane. Following the 1- and 5-min mouthwash treatments, 5.2 and 9.4% of the administered doses were absorbed, respectively. PMID- 1866376 TI - Dose-dependent pharmacokinetics of MK-417, a potent carbonic anhydrase inhibitor, in experimental polycythemic and anemic rats. AB - MK-417 is a potent carbonic anhydrase inhibitor currently under clinical investigation as a topical ocular hypotensive agent. While present in most of the tissues, carbonic anhydrase predominates in red blood cells. Earlier studies from our laboratory have demonstrated that carbonic anhydrase plays an important role in the elimination kinetics of MK-417 and that the enzyme can be saturated when MK-417 exceeds the stoichiometric concentration of the enzyme. Since carbonic anhydrase is an intracellular enzyme in erythrocytes, conditions which may change the hematocrit can alter the load of MK-417 needed to saturate carbonic anhydrase. It is, therefore, important to determine the effects of anemic and polycythemic states on the pharmacokinetics of MK-417. The anemic state in rats was obtained by replacing whole blood with donor plasma (12-15 ml), while polycythemia was induced by infusion of 12 to 15 ml of whole blood. At low doses (0.05 and 0.1 mg/kg), the pharmacokinetic parameters for MK-417 remained unchanged and there were no significant differences in the pharmacokinetic parameters among the anemic, polycythemic, and normal rats. The total blood clearance and apparent volume of distribution were increased markedly when the dose exceeded 0.2 mg/kg in anemic rats and 0.5 and 1 mg/kg in normal and polycythemic rats, respectively. Clearly, the dose of MK-417 required to saturate the enzyme was different among the three groups of animals. However, the terminal half-life was dose independent and not influenced by hematocrit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866377 TI - "On-off" thermocontrol of solute transport. II. Solute release from thermosensitive hydrogels. AB - Poly(N-isopropylacrylamide) (NIPAAm)/polytetramethylene ether glycol (PTMEG) interpenetrating polymer networks (IPNs) were synthesized and their feasibility as thermosensitive hydrogels for drug release was investigated. The release of indomethacin incorporated into these matrices showed pulsatile patterns in response to temperature changes and was sensitive to a few degrees of temperature fluctuation. The temperature inducing on-off release deviated from the gel collapse temperature of unloaded gel, possibly because of solute effects on network properties. The lag time and release profile of indomethacin in the low temperature region (on process) of each temperature cycle were affected by the gel composition and applied temperature. The results of this study demonstrate that solute release can be regulated by rapid deswelling of the surface of the gels in response to temperature. PMID- 1866378 TI - Formulation and in vitro evaluation of pressurized inhalation aerosols containing isotropic systems of lecithin and water. AB - Reverse micellization of nonionic surfactants in apolar media was applied to the formation of solution phase, pressurized inhalation aerosols, employing soya lecithin (SPC) and water in chlorofluorocarbon (CFC) blends. The use of a 30/70 mixture of trichlorofluoromethane (P11) and dichlorodifluoromethane (P12) resulted in the formation of stable, isotropic systems containing 0.5-2.0% (w/v) SPC and solubilized water; R (moles water/moles SPC), 0.9 to 4.28. In systems containing less than 30% P11, phase separation became apparent, particularly at higher water and surfactant concentrations. Dramatic changes in solution viscosity were noted on increasing R values and were attributed to an increase in asymmetry of SPC micelles. Dynamic fractionation of the output from pressurized aerosols using a four-stage liquid impinger showed that the respirable fraction (as measured by the percentage of emitted droplets with aerodynamic diameters less than 5.5 microns) was highly dependent on SPC concentration and R. A significant correlation between RF and actuator score, based on orifice diameter and length, was also found and confirmed that the highest RF values were achieved with the systems of lowest SPC and water concentrations sprayed through an actuator with the smallest and shortest orifice dimensions. This novel mechanism for the formulation of hydrophilic drugs as solutions within CFC-based pressurized aerosols may offer advantages over the traditional suspension approach to pulmonary drug delivery. PMID- 1866379 TI - Significance of partial and total cohesion parameters of pharmaceutical solids determined from dissolution calorimetric measurements. AB - The total and partial adhesion-derived cohesion parameters of three solid pharmaceutical substances (caffeine, theophylline, and phenylbutazone) were determined from dissolution calorimetric measurements, a new technique devised for this purpose. Calorimetry has the advantage of leading directly to enthalpies, from which the solute cohesion parameter(s) is(are) deduced. An equation was developed that relates partial molar enthalpies of mixing (obtained by subtracting enthalpies of fusion from enthalpies of dissolution) to the cohesion parameters of the solute and of the solvents. Solvents were selected on the basis of their known cohesion parameters by applying the experimental research methodology. PMID- 1866380 TI - Crystal growth kinetics of theophylline monohydrate. AB - The crystal growth kinetics of theophylline monohydrate from aqueous buffered supersaturated solutions were investigated at 10, 20, 30, and 40 degrees C. Crystallization experiments were carried out isothermally at pH 6. During growth the crystal count and size distributions were monitored in situ. The growth rate was evaluated from the rate of change of the size with time at a constant value of the size distribution. The growth rate is independent of the stirring rate and the activation energy for growth is higher than the value for simple diffusion, 14.3 and 4.4 kcal/mol, respectively. This indicates that crystal growth of theophylline monohydrate is controlled by a surface reaction mechanism rather than by solute diffusion in the bulk. The growth-rate dependence on the supersaturation was compared with crystal growth theories. The data are described by the screw dislocation model and by the parabolic law, suggesting a defect mediated growth mechanism rather than a surface nucleation mechanism. PMID- 1866382 TI - Determination of allopurinol and oxypurinol in rat plasma, intestinal wash, and bile by high-performance liquid chromatography with electrochemical detection (HPLC/EC) following automated solid phase extraction. PMID- 1866381 TI - Lipophilic peptides: synthesis of lauroyl thyrotropin-releasing hormone and its biological activity. AB - Thyrotropin-releasing hormone (TRH) was derivatized by chemical attachment of lauric acid to the N-terminal pyroglutamyl group. The product was confirmed to be more lipophilic than TRH by high-performance liquid chromatography and measurement of partition coefficients. The central nervous system activity and endocrine activity of the lauroyl derivative were only slightly reduced, to 81 and 64% of the parent TRH, respectively. Lipophilic derivatization may be generally applicable to transmembrane delivery of peptides. PMID- 1866383 TI - The cytotoxicity of p-chloro-m-xylenol in primary culture of rat hepatocytes. PMID- 1866384 TI - Low first-spray drug content in albuterol metered-dose inhalers. PMID- 1866385 TI - Influence of temperature and hydrophobic group-associated icebergs on the activation energy of drug decomposition and its implication in drug shelf-life prediction. PMID- 1866386 TI - Relationship between red blood cell potassium and plasma digitoxin concentrations in intoxicated patients. AB - After severe acute self-poisoning by cardiac glycosides, significant and persistent depletion of red blood cell K+ due to inhibition of Na+K+ ATPase is seen. Because of a delay between the time course of plasma digitalis concentrations and that of red blood cell K+ depletion, no direct relation exists between the two, and RBC K+ has hitherto not been considered useful as prognostic indicators of clinical outcome. In an effort to solve this problem, red blood cell K+ was measured by atomic absorption spectrophotometry and plasma digitoxin concentration assayed in six patients admitted to an intensive care unit after digitoxin self-poisoning. Using the effect compartment model of Sheiner, a relationship based on a sigmoid Emax model was able to relate the digitoxin concentration at the action site to red blood cell K+ depletion. Thus the duration of red blood cell K+ depletion could be predicted from two relative simple in vitro assays. Since RBC K+ is a marker of the inhibition of Na+K+ ATPase by digitoxin, this method could be of use for the management of patients self-poisoned with digitalis. PMID- 1866387 TI - Modulation of ouabain binding in beating ventricular myocardium from guinea-pigs: effects of lidocaine and monensin. AB - To further elucidate the interdependence between digitalis sensitivity and the cellular Na+ load, the influence of two Na+ load modifying drugs, monensin and lidocaine, on the concentration-dependence of ouabain binding and ouabain effects was studied in beating ventricular strips from guinea-pig heart. Monensin (3 x 10(-6)M), a Na+ ionophore known to elevate Na+ influx, enhanced 3H-ouabain binding (by approximately 40%) as well as the ouabain effect at non-toxic ouabain concentrations, and it shifted the threshold for toxicity towards threefold lower ouabain concentrations. Lidocaine (2 x 10(-4)M), a Na+ channel blocker, lowered ouabain binding by about one third, and it extended the ouabain concentration range tolerated without toxicity by a factor of three. In the concentrations used, neither compound exerted any direct effect on ouabain binding studied in isolated cardiac membranes. The binding data obtained in the muscle strips were well fitted by a mathematical model which quantifies the dependence of ouabain binding on the underlying (Na+ +K+)-ATPase activity. These findings provide evidence for an indirect drug-induced modulation of ouabain binding via the interference with the cellular Na+ load. PMID- 1866388 TI - Improvement of glucose homeostasis by oral vanadyl or vanadate treatment in diabetic rats is accompanied by negative side effects. AB - Vanadate and vanadyl, two forms of vanadium, have been reported to exert insulin like effects in vivo and in vitro. In the present study we compared the effectiveness of oral sodium metavanadate (NaVO3), sodium orthovanadate (Na3VO4) and vanadyl sulphate pentahydrate (VOSO4.5H2O) treatment in alleviating some signs of diabetes in streptozotocin-induced diabetic rats. Vanadium compounds were administered in aqueous solutions of NaCl (80 mM) at concentrations of 0.20 mg/ml (NaVO3), 0.50 mg/ml (Na3VO4), and 1.1 mg/ml (VOSO4.5H2O) for two weeks. Control rats, either diabetic or non-diabetic, drank solutions of NaCl (80 mM). Although some signs of diabetes (hyperglycaemia, hyperphagia, polydipsia) were significantly ameliorated by the vanadium treatment, negative side effects were also observed in all of the vanadium-treated diabetic rats. Those effects included some deaths, decreased weight gain, and tissue vanadium accumulation, which are consistent with the reported toxicity of vanadium in non-diabetic rats. Vanadyl sulphate was the most effective compound of those tested in normalizing blood glucose levels. However, the results here reported suggest that chronic administration of vanadyl or vanadate in the drinking water is not a viable alternative treatment to insulin in human diabetes. PMID- 1866389 TI - Increased urinary calcium and magnesium excretion in rats injected with mercuric chloride. AB - Mercuric chloride (HgCl2) is a classic nephrotoxic agent. While it is well established that HgCl2 can induce metallothionein synthesis in the kidney and also cause damage to the pars recta region of the renal tubule, the urinary losses of essential elements like calcium (Ca) and magnesium (Mg) probably related to this process, have not been described. In this study, calcium, magnesium, metallothionein (MT), as well as sodium (Na) and potassium (K) in urine, kidney cortex and liver were measured in male Wistar rats after two daily injections of HgCl2 (0.5 or 1.0 mg Hg/kg body weight intraperitoneally). As compared with controls, there was a significant 3-4-fold increase in calcium excretion which reached its maximum at 8-12 and 32-36 hr after treatment with 1.0 mg Hg/kg. Urinary magnesium excretion was also increased in a similar way as the calcium excretion. At 12-16 hr, urinary magnesium in the 1.0 mg Hg/kg dose group was 3.4 times higher than that of the controls. Urinary MT level in HgCl2 treated rats was much higher than that in the controls, the maximum excretion was between 24-28 and 32-36 hrs preceeded by the peak of Hg in urine. Na and K concentrations in urine decreased significantly in rats treated with HgCl2. The present study thus demonstrates that increases of urinary calcium and magnesium excretion are early toxic effects of HgCl2 on the kidney. It gives support to the hypotheses implying these ion imbalances in the mechanism of elicitation of renal toxicity by mercury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866391 TI - Acute haemodynamic effects of felodipine, verapamil and hydralazine in the anaesthetized dog. AB - Felodipine, a potent dihydropyridine calcium antagonist with a pronounced vascular selectivity, was given intravenously (0.006-0.025 mumol kg-1) to anaesthetized, open-chest dogs with denervated hearts. The result was a dose dependent decrease in mean arterial pressure (MAP) and total peripheral resistance (TPR), while heart rate (HR), stroke volume (SV) and left ventricular end-diastolic pressure remained relatively unchanged. Cardiac tension work (TTI) and oxygen consumption (MVO2) were reduced, probably due to the decrease in afterload. The relative reduction of the coronary vascular resistance (CVR) was greater than that of TPR. The hypotensive effect of verapamil (0.05-0.20 mumol kg 1) was small and MAP decreased mainly via a decrease in HR and SV. Higher doses of verapamil which induced vasodilatation could not be given without the development of complete atrio-ventricular dissociation. Hydralazine (11-45 mumol kg-1) decreased TPR and CVR in parallel but the decrease in MAP was partly counteracted by a powerful increase in HR, SV and cardiac inotropy which was associated with elevated catecholamine levels in plasma. When MAP and HR were maintained constant by means of aortic balloon inflation and atrial pacing, felodipine markedly increased coronary blood flow and coronary sinus oxygen saturation while SV, TTI, inotropy and MVO2 remained relatively unchanged. It is concluded that felodipine markedly dilates peripheral resistance vessels, and in particular those in the coronary vascular bed, without any cardiodepressant effects. PMID- 1866390 TI - Theophylline effects on phasic tension and slow inward current of isolated frog atrial fibres: influence on the action of isoprenaline. AB - The action of theophylline on phasic tension and slow inward current (Isi) was investigated on isolated voltaged-clamped frog atrial fibres. The action of theophylline was both dose- and time-dependent; the most effective dose was 2.10( 3)M. Theophylline induced a rapid positive inotropic effect which cannot be attributed to a beta-adrenoceptor stimulation or to an adenosine antagonism; this effect was closely related to an increase in slow inward current (Isi), probably due to an inhibition of phosphodiesterase activity and a subsequent increase in cAMP content. The decline of the positive inotropic effect of theophylline was discussed in terms of additional effects of the drug. Theophylline, consistently with its phosphodiesterase inhibitory action, was shown to potentiate the effects of isoprenaline on phasic tension and Isi; however no potentiation was observed after reserpine-induced depletion of endogenous catecholamines. It might be thought that non-specific effects of reserpine on some steps of cardiac excitation-contraction coupling counteract the effects of theophylline. PMID- 1866392 TI - [Nocturnal respiratory and circulatory disturbances. Meeting of the work group of the German Society for Pneumology. Berlin, 11-12 May 1990]. PMID- 1866393 TI - [Relationship between insomnia and arterial hypotension]. AB - The relations between insomnia and blood pressure were investigated in 151 patients (56 men and 95 women). It was found that 37.1% of the patients were normotensive, whereas 31.8% suffered from arterial hypertension and 31.1% from arterial hypotension. There was practically no difference between normotensives and hypertensives in respect of disturbed behavioral patterns of sleep, but an entirely different picture was presented by the arterial hypotensives. Characteristic features of hypotonic insomnias were (mostly in women) prolonged time before falling asleep, frequent awakening at night associated with tachycardia and long-lasting increased excitability, starting difficulties in the morning, depressive conditions, compulsive yawning and falling asleep during daytime, tiredness, lack of "drive" and reduced physical and mental efficiency. This pattern of signs and symptoms was enhanced by hypnotics and tranquilisers. During sleep blood pressures down to 50/35 Torr were measured. It is assumed that the low blood pressure results in hypoxic and hypoglycaemic conditions in the brain. Spontaneous awakening is considered to be an emergency reaction triggered by the deficient cerebral blood flow. PMID- 1866394 TI - [Evaluation of an anamnesis questionnaire for the diagnosis of sleep apnea in patients with chronic diseases of the respiratory organs]. AB - In a Rehabilitation Clinic for Diseases of the Respiratory Organs we examined 497 male patients aged 45.9 +/- 11.1 years with a relative weight of 109 +/- 16.7% who were suffering from chronic diseases of the respiratory tract (66.2% chronic bronchitis, 33.8% asthma bronchiale, 49.6% obstruction of the respiratory tract). They were subjected to a detailed physical examination and were given an anamnestic questionnaire for the purpose of diagnosing sleep-related respiratory disturbances (Siegrist et al., 1987). In addition, whole body plethysmography was performed in all patients as well as a pulse-oximetric examination during night sleep. Using factor analysis, it was possible to extract 5 factors from the 23 items of the anamnesis questionnaire. With these 5 factors, 60.5% of the total variance could be explained. These factors describe: 1. Dyspnoea (35.3%); 2. Vigilance (8.5%); 3. Sleep disturbances (6.3%); 4. Headache (5.8%) and 5. Snoring (4.7%). Different factor patterns are seen for different groups of patients. In patients suspected of an obstructive sleep apnoea syndrome, however, it will always be necessary to perform further stage-wise diagnosis to safeguard the diagnosis. PMID- 1866395 TI - [Ambulatory monitoring of frequency of apnea in patients with suspected sleep apnea syndrome. Comparative studies using a thermistor sensor]. AB - To record and evaluate the number and duration of nocturnal apneas, and easy method is needed in an outpatient setting. New methods such as recording the tracheal sounds, heart frequency, and O2 saturation, are now available. Recording of thermal convection by Thermistor has not been performed on an outpatient basis so far. Hence, we developed a method by which a thermistor was placed on a mask to record the nasal and oral flow. A specially developed computer hardware evaluates date, time, period, number and mean values of the apneas. The parameters were compared with the conventional methods of recording apneas (thoracic and abdominal movement. O2 saturation, heart frequency and 3 thermistors at mouth and nose). 20 patients, mean age 53.1 +/- 1.6 years, were examined. In 12 patients the apnea frequency was between 0 and 50 apneas per night, in 8 between 50 and 550. Patients with an apnea frequency of more than 50 per night (polygraphy) could be identified with the thermistor method. Our results show that the method is sensitive in respect of the oral and nasal flow. The method seems valid to differentiate between normal persons and patients with increased risk of apnea syndrome. PMID- 1866396 TI - [Computer analysis of disturbed respiration in patients with sleep apnea]. AB - In patients with sleep related breathing disorders parallel evaluation of respiration, blood gases and the EEG are indispensible. Computerized methods can provide a detailed analysis of the interrelation of these parameters to enlighten the disturbed central regulation of respiration in these patients. These methods also can help to achieve a better differential diagnosis in routine clinical work. A new method is presented here which evaluates the signals of nasal airflow, thoracic and abdominal movements together with oxygen saturation and heart rate in parallel. The new method is validated using a detailed visual analysis. Results prove the usefulness of the new method. To apply the method the relationship between length of apnea and oxygen desaturation is evaluated for different sleep stages separately. PMID- 1866397 TI - [Assessment of the MESAM and Biox 3700 early warning methods for the diagnosis of sleep-related respiratory disorders in young men]. AB - We can use pulse oximetry as a method for diagnosis of the sleep apnoea syndrome, as well as L-EKG, MESAM II and the actigraph. In this study MESAM II and pulse oximetry were combined for finding out discrete sleep-related breathing disorders. The results were compared with polysomnography. 5 (15.1%) of 32 patients had an index of apnoea (AI) greater than 10, whereas 4 (12.1%) patients showed an AI greater than 5. All of the patients with positive signs in MESAM II/pulse oximetry had an AI greater than 5 in polysomnography, whereas non of the patients with negative signs in MESAM II/pulse oximetry had an AI greater than 5 in polysomnography. PMID- 1866398 TI - [SIDAS 2010: mobile 10-channel unit for the diagnosis of sleep-related respiratory disorders]. AB - At the moment diagnosis of sleep related breathing disorders (SRBD) is carried out in specialised clinical centres with well-equipped sleep laboratories. Since there are only few of these in Germany, medical care in this field is not sufficient at all even if applied only to high-risk patients. To cope with the large number of patients with severe SRBD we developed a mobile 10-channel unit (SIDAS 2010) designed for diagnosing SRBD even outside the conventional sleep laboratories. In this study we investigated 108 patients who after using the 4 channel recorder presented signs and symptoms suggesting SRBD. After evaluating the tracings in 53 patients a distinct obstructive sleep apnoea (OSA) (AI 10) could be diagnosed; in 55 patients the signs remained indistinguishable. In 2 recordings with SIDAS in 74 patients, a distinct OSA was diagnosed, 34 patients had an AI less than 10; these patients underwent renewed polysomnographic recordings with EEG in addition. The polysomnographic recordings revealed 5 patients with an AI between 5 and 10.3 with primary and secondary alveolar obstructive hypoventilation due to excessive snoring. The comparison of SIDAS recordings with recordings made by polysomnography proved SIDAS to be valuable in respect of diagnosing type of SRBD (obstructive/central) and amount of respiratory events (apneas/hypopnoeas). In this study only 13 patients with SRBD (14.9%) need further diagnostic procedures. We conclude that with SIDAS most of the SRBD can be diagnosed sufficiently even outside conventional sleep laboratories. PMID- 1866399 TI - [Assessment of cyclic and phasic oxygen saturation using pulse oximetry in the diagnosis of nocturnal respiratory disorders]. AB - Nocturnal pulse oximetry is frequently used in screening studies when diagnosing nocturnal respiratory disorders. Short-term cyclic desaturations of oxygen can serve to indicate recurring apnoeas, whereas long-lasting phasic reductions of oxygen saturation are predominantly seen in hypoventilation. However, there are no uniform assessment criteria. We developed a computer programme for the differentiated assessment of cyclic and phasic oxygen desaturations. With this programme it is possible to characterise the individual phases in respect of gradient and duration of the decrease in oxygen saturation, of the starting, minimal and final values and the total duration of the desaturation phase. This enables determination of the rate of incidence of various forms of desaturation during nocturnal recording. The results of this differentiated analysis of nocturnal pulse oximetry in patients with sleep apnoea syndrome (n = 6) and with chronic obstructive airways disease with respiratory insufficiency (n = 6) and without respiratory insufficiency (n = 6) are demonstrated as model examples. PMID- 1866400 TI - [Pulmonary artery blood pressure and snoring]. AB - Snoring is an extrathoracic inspiratory airway obstruction during sleep, accompanied by more or less intense noise. The inspiration volume being limited at the same time, this can produce additional blood gas changes. Epidemiological studies have shown an increased risk of myocardial infarction or cerebral ischaemia during night for snorers. Little is known, however, about acute effects of snoring on the haemodynamics of heart and circulation. The present study presents data of the pulmonary artery blood pressure during sleep-related upper airway obstruction. Pulmonary arterial pressure during sleep was examined with five patients via Swan-Ganz catheter. When an upper airway obstruction occurred, the inspiratory pulmonary arterial pressures rose in all the five patients. Two patients showed a clinically significant decrease in arterial oxygen saturation during snoring so that in these cases, a hypoxic vasoconstriction can be discussed as a possible cause. The other three patients did not produce significant decreases in oxygen saturation, so that in these cases mechanical factors (negative inspiratory intrathoracic pressure oscillations) should be regarded as the most probable cause for increases in the pulmonary arterial blood pressure. PMID- 1866401 TI - [Which factors promote chronic alveolar hypoventilation in patients with obstructive sleep apnea?]. AB - The pathogenesis of obesity hypoventilation is incompletely understood. We investigated 505 patients with sleep apnoea in respect of determinants that correlate with chronic hypercapnia. 14 patients (2.8 per cent) exhibited daytime hypercapnia (PCO2 greater than or equal to 45 mmHg). Compared with the entire group of patients, these patients showed heavier overweight (p less than 0.001) and their nightly respiratory dysregulation defined by the apnoea index was more severe (p less than 0.001). If these patients were compared with 14 normocapnic controls matched for apnoea index, weight and age, there was no difference in respect of lung function data. We conclude that overweight and the severity of sleep apnoea are determinants that predispose to chronic alveolar hypoventilation. PMID- 1866402 TI - [Sleep-related respiratory disorders and coronary heart disease]. AB - A review of the literature shows that more than 50% of examined patients suffering from coronary heart disease were also suffering from sleep-related apnea. We were able to diagnose a pathological sleep apnea in 9 out of 25 patients (36%) suffering from an angiographically confirmed coronary 2-vessel and 3-vessel disorder. Patients with this combination--this is the hypothesis derived from our study--are at risk due to nocturnal apnea-induced myocardial ischaemia and rhythmic disorders. In 15 patients with sleep apnea and coronary heart disease or small vessel disease, nocturnal polysomnography was conducted, in parallel a 6-channel ECG was recorded. The apnea index (second night) was on the average 33 phases/h, the maximal duration of an apnea phases being 120 seconds. The minimal blood gas saturation recorded during sleep was between 46 and 89% (median 76.0%). In 4 of the 15 patients it was possible to confirm myocardial ischaemia (correlated via REM and also via NREM) with a maximum duration of 60 seconds, mainly during the phases of maximal apnea activity and blood gas desaturation. On comparing the ventricular arrhythmias waking/sleep, the Lown class did not change in 12 patients; there was deterioration in 2 patients and in one patient a qualitative improvement during the sleep phase. Patients suffering from sleep-related respiratory disorders and coronary heart disease are at cardiac risk, the more so since long-lasting apneas can lead to conditions of hypoxia at the heart in pre-existing changes in the coronary arteries, restricted coronary reserves and reduced tolerance to hypoxia. Such hypoxia can in turn induce enhanced electrical instability and a disturbance of the contractile function. PMID- 1866403 TI - [Oxygen saturation and sleep structure in patients with dilated cardiomyopathy]. AB - It is known that patients suffering from severe cardiomyopathy may develop cyclic changes in breathing (Cheyne-Stokes-breathing) (2, 3). Coughing and dyspnea may be linked to periodic breathing. Specific detailed polysomnographic studies of sleep architecture and oxygen saturation have not been published. Eight patients suffering from dilatative cardiomyopathy (NYHA III-IV) were studied by pulse oximetry and polysomnography. Six of eight patients had severe breathing irregularities. These disturbances became manifest partially as Cheyne-Stokes breathing, partially as central sleep apnea. During these periods, oxygen saturation dropped as far as to 65 per cent of the original level. PMID- 1866404 TI - [Nocturnal oxygen saturation in patients with coronary heart disease--dependent on degree of left ventricular functional impairment]. AB - It is assumed, that patients with coronary heart disease (CHD) more often suffer from sleep related disorders of breathing than healthy subjects. A relation to an impaired left ventricular performance is discussed. In 40 CHD-patients and 30 cardio-respiratory healthy controls we therefore measured arterial oxygenation during sleep by means of pulse-oximetry. Our results show a marked increase in the frequency of nocturnal oxygen-desaturations along with the degree of impaired left ventricular function independent of a special sleep apnea risk. In case of cardiac insufficiency at rest cyclical oxygen-desaturations were observed ten times as often as in the healthy controls. A central disturbance of the respiratory control, which leads to periodic breathing (type Cheyne-Stokes) has to be discussed. Because of the general high risk of CHD-patients concerning the development of nocturnal complications of their disease, sleep-related disturbances of ventilation have to be detected early by means of routinely applied screening-methods. PMID- 1866405 TI - [Cardiopulmonary risk factors in patients with sleep apnea]. AB - Since the interaction between disorders of the respiratory coordination and cardiovascular or cardiopulmonary regulation is still largely unknown the intention of the present investigation is to point out the coincidence of cardiac arrhythmias, such as premature ventricular capture (PVC) beats and conduction blocks, with obstructive sleep apnea (OSA). For the first time a group of more than 300 patients with suspected OSA is examined concerning risk factors and frequent diagnoses as obesity, hypertension, coronary heart disease (CHD), heart insufficiency, chronic obstructive pulmonary disease (COPD), and daytime hypoxaemia. Summarizing the results of lung function test, blood gas analysis, strain-ECG, Holter-ECG and inductive plethysmography with oxygen partial pressure measurement by ambulatory work-up the following statements can be made: PVC beats occurring markedly during sleep give hints for OSA being the underlying cause, especially if the patients are young and overweight. Hypoxaemia increasing during the apnea episodes should be considered as one possible pathogenetic mechanism. Second- and third degree conduction blocks and sinus arrest coincident very often with OSA. They suggest to be life-limiting factors the more so since they often go along with CHD or heart insufficiency. Systemic arterial hypertension and overweight have the highest prevalence in OSA, signs for heart insufficiency and daytime hypoxaemia are also significantly more frequent than in non-OSA patients. We could find no hints for direct pathogenetic coherence between CHD and OSA or between COPD and OSA, nevertheless pronounced nocturnal changes in blood gases and intrathoracic hemodynamics have important influence on the cardiopulmonary and cardiovascular system, as partly illuminated in other more pathogenetic oriented studies by the present time. PMID- 1866406 TI - [Risk of accidents in patients with nocturnal respiration disorders]. AB - Excessive daytime sleepiness is one of the main symptoms of sleep apnoea, which can, especially in monotonous situations, lead to real nodding off. Since driving a motor vehicle can also be monotonous, patients suffering from untreated sleep apnoea may be a possible traffic risk. Before undergoing a polysomnographic examination, 123 patients filled in a questionnaire inquiring about fatigue and sleepiness while driving a vehicle as well as accidents during the past three years. Five groups were formed according to severity of sleep apnoea. Right through these groups, the increase in heavy fatigue during driving (median) was significant: from "seldom" (AI less than 5) via "sometimes" to "often" (AI greater than or equal to 35). Occurrences of short periods of falling asleep (means) were practically not reported (0.02) by the group without sleep apnoea but increased considerably to 3.37 times per 1000 km for the group with an AI greater than or equal to 35. The frequency of accidents due to sleepiness rises significantly in concurrence with the seriousness of sleep apnoea. Besides, patients with an AI greater than or equal to 5 attribute 23 out of 28 accidents to sleepiness, whereas patients without sleep apnoea attribute all four accidents to other reasons (p = .0035). These findings emphasise the importance of an early diagnosis and effective therapy of sleep apnoea - which is available as nasal continuous positive airway pressure ventilation (nCPAP). Sleep medicine can thus not only help patients suffering from sleep apnoea but may also reduce the health risk of other traffic participants and be cost-saving. PMID- 1866407 TI - [Drug therapy of sleep-related respiration disorders]. PMID- 1866408 TI - [Comparative studies on the effect of nasal CPAP, theophylline and oxygen in patients with sleep apnea syndrome]. AB - In patients with sleep apnea-syndrome nasal CPAP-therapy is the method of choice. The apnea phases are practically completely eliminated. However some patients with SAS don't accept CPAP-therapy. In this group Theophylline or O2-therapy respectively is discussed. We examined therefore 21 patients (55.8 +/- 9 years) with sleep-apnea syndrome and an apnea-index of 39 +/- 19.9 during 4 consecutive nights (diagnosis, nCPAP-therapy, O2-therapy by 21/min, by nasal prongs and Theophylline 375-400 mg in the evening and calculated apnea-index, the longest apnea and the lowest O2-saturation. On CPAP the number of apneas was practically reduced to 0. On Theophylline there was a relevant reduction of the apnea frequency. On O2-therapy only few patients with non-compliance Theophylline therapy can be of some benefit in patients with moderate sleep-apnea syndrome. However the apnea-index cannot be normalized. PMID- 1866409 TI - [Surgical therapy of obstructive sleep apnea syndromes: results of the Ulm treatment program]. AB - The article reports on the results obtained by uvulopalatopharyngoplastic surgery (= UPPPS) in 31 patients suffering from obstructive sleep apnoea syndrome (= OSAS) and in 9 patients with habitual or obstructive snoring. All patients were subjected to thorough preoperative examination including rhinometry, nasopharyngeal video-endoscopy, radiocephalometry and polysomnography. In 8 out of 9 (89%) of the habitually snoring patients and in 17 of 31 (55%) of OSAS patients, surgery was successful. In these patients, a postoperative respiratory disturbance index (RDI) of less than 10 was recorded, whereas in 4 patients (13%) the postoperative RDI was between 10 and 15. Ten patients did not respond satisfactorily to UPPPS (32%). RDI was postoperatively still above 15. Analysis of patient data shows that almost all habitually snoring patients and the OSAS patients with slight overweight and low to medium apnoea index were successfully treated with UPPPS. In accordance with these results a treatment concept has been drawn up for OSAS patients that takes stock of all the possibilities and limitations of available conservative and surgical treatment methods. PMID- 1866410 TI - [Therapy of sleep apnea with theophylline (Uniphylline) administration every evening]. AB - Sleep apnoea (SA) has a prevalence of 1-10% in men. The physiological sleep is disturbed. SA is associated with cardiopulmonary disease (systemic arterial hypertension, cardiac arrhythmics, cor pulmonale) and the quality of the patient's life is reduced. Thirty male patients participated in a study to investigate the influence of an oral dose of theophylline on sleep apnoea. Under theophylline a significant reduction of apnoea events and of the apnoea index was seen. PMID- 1866411 TI - [Long-term follow-up of sleep apnea therapy with sustained-release theophylline administered every evening]. AB - Sleep apnoea increases mortality and morbidity. The physiological sleep profile is disturbed and functional capacity is decreased. At present nasal CPAP breathing (continuous positive airway pressure) seems to be the best treatment method in obstructive sleep apnoea. However, this therapy is expensive, imposing a strain on the patient, and hence some patients will not tolerate it. Medical treatment of sleep apnoea with theophylline has proved effective. In 40 patients suffering from sleep apnoea, long-term treatment with sustained-release theophylline was investigated. Responders show a significant reduction of apnoeic phases and of apnoea index at the beginning and after long-term treatment. Using an individual theophylline dosage with morning theophylline concentration between 5 and 8 micrograms/ml, only few side-effects occurred. Positive effects on cardiopulmonary capacity could be detected. The Broca index does not change significantly. Sustained-release theophylline applied in the evening showed a positive effect on sleep apnoea in responders. PMID- 1866412 TI - [Hemodynamic changes with and without CPAP-ventilation in patients with sleep apnea]. AB - In 21 patients suffering from severe sleep-apnoea syndrome we measured continuously haemodynamic parameters, blood gases, ECG, EEG, respiratory rate and ultrasonic cardiogram before and under treatment with nasal CPAP-breathing. All patients (male, age 29 to 58 yrs) had normal blood gases, heart-minute-volumes pulmonary artery pressures and left ventricular end-diastolic wedge pressures, when they were awake. During sleep all developed a decrease of pO2 and severe pulmonary artery hypertension with mean pulmonary artery pressures of 64 mmHg. In 10 patients an enlargement of the right ventricular diameter up to 13 mm difference could be seen. Treatment with nasal CPAP-breathing could reduce or even prevent changes in blood gases and in the haemodynamic system. The pulmonary artery pressures normalised in all patients. No right ventricular enlargement could be seen during nasal CPAP-breathing. Treatment with CPAP-breathing could normalise haemodynamic disorders in patients with severe SAS and may perhaps prevent development of cor pulmonale. PMID- 1866413 TI - [Treatment of primary and secondary therapy failure in patients with sleep apnea treated with nasal CPAP]. AB - Two forms of treatment failure of nCPAP therapy should be distinguished: 1. Primary treatment failure: the reversal of apnoeas and hypopnoeas cannot be achieved due to central SA or a combination of MSA and central hypoventilation. In 10 patients who did not respond to nCPAP (7 patients with purely central SA and 3 patients with MSA who still demonstrated long phases of central hypoventilation during nCPAP) we performed a nasal intermittent positive pressure ventilation (nIPPV) during at least 3 treatment nights. In all patients a reversal of apnoeas and hypopnoeas could be achieved, despite a few phases of mask leakage. Due to possibly life threatening side effects continuous monitoring is required during the initial treatment phase. 8 patients who reported a reduction of symptoms have been successfully using the treatment at home for up to 22 months. 2. Secondary treatment failure: nCPAP leads to a normalisation of breathing pattern but patients refuse nCPAP or discontinue treatment. Besides patients who are poorly motivated there are four major side effects of nCPAP as a reason for non-compliance: a) drying out of the nasopharyngeal mucosa or rhinitis; b) pressure marks caused by the nose mask; c) intolerance to the high expiratory pressure; d) noise. Drying out of the mucosa and rhinitis are the most important side effects. If an increase of room temperature and humidity, nasal cream and small amounts of mint-oil as well as a heat-moisture exchanger (HME) prove inadequate, we use a heated humidifier (Drager, Aquapor).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866414 TI - [Increase in blood pressure due to continuous obstructive snoring]. AB - Sleep-related breathing disorders can strain the cardiovascular system. Link-ups with arterial hypertension have been confirmed in obstructive or mixed sleep apnoea which is characterised by discontinuous nocturnal snoring. On the other hand, it is known that arterial hypertension is very frequently seen in snorers. The present study deals with short-term, breathing-related blood pressure patterns and blood pressure changes during the snoring phase. 18 obstructive snoring phases were identified in 4 male patients aged 50 years (42-65), Broca index 136 (119-171). Polysomnographic measurements were carried out in the sleep laboratory and the blood pressure was continuously recorded via the a. brachialis. The short-term breathing-dependent blood pressure changes were systolic 10.8 (10-30) mmHg at the beginning and 17.5 (10-30) mmHg at the end of the snoring phase (P less than 0.01). Diastolically there was a difference of 9.4 (5-15) mmHg versus 13.9 (5-25) mmHg (P less than 0.01). During the snoring phases the systolic blood pressure increased from 140.3 (120-190) mmHg to 170.0 (145 235) mmHg and the diastolic pressure from 69.7 (50-110) mmHg to 93.1 (70-120) mmHg. The study proves that blood pressure increases occur not only in apnoeic snoring but also in continuous obstructive snoring. It is suspected that these changes are responsible for the high frequency of arterial hypertension among continuous snorers. PMID- 1866415 TI - Peripheral chemoreceptor reflex in obstructive sleep apnea patients; a relationship between ventilatory response to hypoxia and nocturnal bradycardia during apnea events. AB - 15 patients with obstructive sleep apnea syndrome and arterial hypertension (H OSAS), 25 normotensive patients with sleep apnea syndrome (N-OSAS) and 20 healthy age-matched controls (C) were included in this study. Ventilatory responses to activation (hypoxia) and inactivation (hyperoxia) of carotid chemoreceptors were studied in all subjects. Relationship between hypoxic ventilatory reactivity and nocturnal bradycardia during apnea-phases was analysed in both groups of patients. Results and conclusions. 1. We found an impairment of ventilatory response to hypoxia in H-OSAS and N-OSAS patients. However, the increase in ventilation in response to hypoxia was significantly greater in H-OSAS as compared to N-OSAS patients. 2. An augmented ventilatory response to inactivation of carotid chemoreceptors (the decrease in ventilation), observed in H-OSAS patients, indicates an increase in resting peripheral chemoreceptors drive in this group of patients. 3. The relationship between ventilatory response to hypoxia and nocturnal bradycaria in obstructive sleep apnea patients suggests, that hypoxic reactivity of arterial chemoreceptors might be involved in the origin of bradycardia during apnea events. PMID- 1866416 TI - Structure and possible function of Plasmodium falciparum proteins exported to the erythrocyte membrane. AB - On infecting the red blood cell, the malaria parasite Plasmodium falciparum induces alterations in the erythrocyte membrane. The parasite appears to synthesize proteins that are exported across the parasitophorous vacuole membrane and through a system of membraneous structures within the cytoplasm of the host cell to the surface membrane of the erythrocyte. There, these proteins are either released or remain associated with the membrane. In this review we describe the structure and discuss the possible functions of some of the exported proteins. PMID- 1866417 TI - Ultrastructural observations and radiometric assay on cercarial penetration and migration of the digenean Diplostomum spathaceum in the rainbow trout Oncorhynchus mykiss. AB - The entrance into host tissues by the cercaria of the digenean Diplostomum spathaceum and the parasite's migration to the eyes of the fish host (post penetration larvae) were studied by scanning and transmission electron microscopy at the ultrastructural level and by a radiometric assay in experimentally infected rainbow trout (Oncorhynchus mykiss). It was demonstrated that cercariae penetrated the host surface at several sites, although the major site involved the gill region. This observation was verified by the measurement of radioactivity in different regions of fish at intervals following their exposure to cercariae that had been radiolabeled with selenium in vivo. The migratory routes of the post-penetration-labeled cercariae (diplostomulum) were followed along with the distribution of radioactivity, which was altered with increasing time after exposure in the different regions of the host. A marked increase in radioactivity was noted, particularly in the eyes of the host, whereas the radiolabel decreased elsewhere. The results support the view that the cercariae of D. spathaceum contact the host by chance. The finding that the parasite mainly penetrates the host through the gills may be connected with fish ventilation hydrodynamics. The total amount of radioactivity retained in the fish gradually decreased with time, which may suggest that only a portion of the primarily attached cercariae actually penetrated the fish. The majority of the penetrating parasites reached the eyes of the host, where they became established as metacercariae within 24 h, thus indicating migration directed to the eye region. This is facilitated by the functional morphology of the migrating stage of D. spathaceum. PMID- 1866418 TI - Improvement of liver resectional therapy by adjuvant chemotherapy in alveolar hydatid disease. Swiss Echinococcosis Study Group (SESG). AB - In human alveolar echinococcosis radical surgery is the only curative therapy. Local recurrences after "radical" surgery have been observed rather frequently in former years. Postoperative "prophylactic" chemotherapy with benzimidazole derivatives over two years appears to prevent local recurrences according to our experience. In addition five patients of our series who suffered from primarily non-resectable alveolar echinococcosis became radically operable after an average of 2 years of chemotherapy. Our experience suggests that chemotherapy improves resectability and curability of surgery in alveolar echinococcosis. PMID- 1866420 TI - Diplectanidae (Monogenea) infestations of sea bass, Dicentrarchus labrax (L.), from the Spanish Mediterranean area. Histopathology and population dynamics under culture conditions. AB - In the present study, Diplectanum laubieri was redescribed from material obtained from wild and cultured fish. The population dynamics of D. aequans and D. laubieri under culture conditions was studied. The prevalence and mean intensity (average number of worms per parasitized fish) were 80.64% and 112 for D. aequans and 67.74% and 59.61 for D. laubieri, respectively. Both Diplectanidae exhibited seasonal variations, with maximal infection levels occurring in winter, suggesting continuous parasites recruitment, and infection levels tended to increase with host age. Male hosts were more heavily infested than females. The apparent positive association between D. aequans and D. laubieri was not confirmed statistically. The Diplectanidae showed definite and different patterns of gill distribution. Histopathological gill damage mainly consisted of hyperplasia of the epithelium, fusion of branchial lamellae and the presence of hemorrhagic and inflammatory foci with leucocytic infiltration. The results demonstrated the pathological importance of both Diplectanidae for the cultivation of sea bass. PMID- 1866419 TI - Thin-layer and liquid column chromatographic analyses of the lipids of adult Onchocerca gibsoni. AB - Lipids were extracted from adult Onchocerca gibsoni with chloroform/methanol and the total lipid content was characterized. Glycolipids were isolated from other lipid classes by Florisil column chromatography and were then fractionated by DEAE-Sephadex ion-exchange chromatography. HPTLC revealed the presence of 9 neutral glycolipid bands and of 15 acidic glycolipid bands that stained for sialic acid with resorcinol. Lipids that contained no carbohydrates were analyzed by a combination of TLC and amino column chromatography. Triacylglycerols, cholesterol, cholesterol esters, and free fatty acids were found to be major components of the neutral lipid fraction, and diacylglycerols and monoacylglycerols were minor components. Phosphatidylethanolamine and phosphatidylcholine were the predominant phospholipids. Phosphatidylserine, phosphatidylinositol, sphingomyelin, lysophosphatidylcholine, and lysophosphatidylethanolamine were also present in significant amounts, whereas only traces of cardiolipin and phosphatidic acid were detected. Several minor lipids and phospholipids remained unidentified. These results indicate that adult O. gibsoni have a nonglycosylated lipid composition resembling that of other parasitic nematodes as well as a substantial repertoire of glycolipids, including many with the characteristics of gangliosides. PMID- 1866421 TI - In vivo efficacy of albendazole against Giardia duodenalis in mice. AB - The antigiardial effects of albendazole were demonstrated in vivo using experimental infections of Giardia duodenalis in mice. These results complement previous in vivo studies in which albendazole was shown to have more potent antigiardial action than the currently applied antigiardial drugs. In mice, 2-4 doses (greater than 100 mg/kg twice daily) were required for complete inhibition of cyst excretion and full elimination of trophozoites from the small intestine. The high doses necessary in mice were not unexpected and are discussed in light of the possible pharmacokinetics of albendazole in the animal model used in this study. PMID- 1866422 TI - In vitro drug sensitivity of Trypanosoma congolense isolates. AB - The sensitivity of Trypanosoma congolense isolates to diminazene and isometamidium was determined using an incorporation assay based on the uptake of [3H]-hypoxanthine in the presence of serial drug dilutions. The bloodstream forms of the different isolates exhibited variation in their sensitivity to the drugs that correlated well with the in vivo drug response. For diminazene, the sensitivity of the most sensitive population was 40 times that of the least sensitive population. For isometamidium, the IC50 values (the drug concentrations that decreased radiolabel incorporation by 50%) lay in a similar range, except for those found for two isolates from lions, which were 10(3)-10(4) times more sensitive than the isolates from cattle. The sensitivity of procyclic forms differed markedly from that of the bloodstream stages. Therefore, it must be concluded that the procyclic stage does not reflect the sensitivity of the bloodstream forms of T. congolense and that the former should not be used for determinations of in vitro drug sensitivity. PMID- 1866424 TI - On the reaction of adult Rhipicephalus evertsi mimeticus and Hyalomma truncatum to horizontally incidenting optical radiation of various wavelengths ranges and different irradiances and to optical radiation of a sun-simulating wavelength spectrum. AB - The valence of horizontally incidenting light/optical radiation for host-seeking inclined ixodid ticks was investigated by exposing male and female adults of Rhipicephalus evertsi mimeticus and Hyalomma truncatum to narrow-band monochromatic radiation in the wavelength range of 300-801 nm at irradiances corresponding to an overcast to clear sunny day, a cloudy day and a full-moon night as well as to optical radiation of a sun-simulating wavelength spectrum of 190-2600 nm within a test chamber from which other stimuli were excluded. It was demonstrated that independent of sex, adult ticks of R. e. mimeticus and H. truncatum responded to a wide wavelength spectrum in the visible and UV range, even at irradiances corresponding to a full-moon night. Interspecific differences existed in the degree and extent of the response as well as in the spectral sensitivity. Ticks of H. truncatum consistently showed a faster and stronger response and reacted phototactically positively in higher percentages than adults of R. e. mimeticus. Independent of wavelength range and irradiance, predominantly only few R. e. mimeticus ticks were stimulated to positive phototaxis, whereas at least 33.3% (in most cases, 50%) and maximally greater than 80% of H. truncatum adults reacted phototactically positively. Spectral sensitivity maxima were demonstrated at the yellow and red light and at the UV-A waveband width for R. e. mimeticus and at the violet, blue, green and yellow light wavelength for H. truncatum. With decreasing irradiance, the spectral sensitivity shifted to the blue wavelength range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866423 TI - Pyrimethamin-resistant Plasmodium falciparum lack cross-resistance to methotrexate and 2,4-diamino-5-(substituted benzyl) pyrimidines. AB - Methotrexate resistance induced in cultured Plasmodium falciparum depends on an altered dihydrofolate reductase with decreased affinity for methotrexate as well as for pyrimethamine. In contrast, pyrimethamine-resistant field isolates of P. falciparum lack cross-resistance to methotrexate and 2,4-diamino-5-(substituted benzyl) pyrimidines. The structure of the latter class was optimized by the use of trimethoprim as a lead and the substitution of methoxy groups at the benzyl ring by 3-(4'-aminophenyl-4-sulfonylphenylamino)propoxy or by (4'-aminophenyl-4 sulfonylphenyl)methoxy, which resulted in antimalarials of high potency. The efficiency of these newly designed 2,4-diamino-5-(substituted benzyl) pyrimidines was confirmed by their strong inhibitory effect on plasmodial dihydrofolate reductase as well as by in vitro screening against drug-sensitive and -resistant strains of P. falciparum. PMID- 1866425 TI - Echinococcus multilocularis: antigenic variance between different parasite isolates. PMID- 1866426 TI - Effects of anti-IgE monoclonal antibody on a primary infection of Strongyloides ratti in mice. PMID- 1866427 TI - Prevalence and distribution of Dicrocoelium dendriticum and Fasciola hepatica infections in cattle in Switzerland. PMID- 1866428 TI - Effects of Eimeria separata on eosinophilia induced by Nippostrongylus brasiliensis. PMID- 1866429 TI - Phospholipase A2 at the bilayer interface. AB - Interfacial catalysis is a necessary consequence for all enzymes that act on amphipathic substrates with a strong tendency to form aggregates in aqueous dispersions. In such cases the catalytic event occurs at the interface of the aggregated substrate, the overall turnover at the interface is processive, and it is influenced the molecular organization and dynamics of the interface. Such enzymes can access the substrate only at the interface because the concentration of solitary monomers of the substrate in the aqueous phase is very low. Moreover, the microinterface between the bound enzyme and the organized substrate not only facilitates formation of the enzyme-substrate complex, but a longer residence time of the enzyme at the substrate interface also promotes high catalytic processivity. Binding of the enzyme to the substrate interface as an additional step in the overall catalytic turnover permits adaptation of the Michaelis-Menten formalism as a basis to account for the kinetics of interfacial catalysis. As shown for the action of phospholipase A2 on bilayer vesicles, binding equilibrium has two extreme kinetic consequences. During catalysis in the scooting mode the enzyme does not leave the surface of the vesicle to which it is bound. On the other hand, in the hopping mode the absorption and desorption steps are a part of the catalytic turnover. In this minireview we elaborate on the factors that control binding of pig pancreatic phospholipase A2 to the bilayer interface. Binding of PLA2 to the interface occurs through ionic interactions and is further promoted by hydrophobic interactions which probably occur along a face of the enzyme, with a hydrophobic collar and a ring of cationic residues, through which the catalytic site is accessible to substrate molecules in the bilayer. An enzyme molecule binds to the surface occupied by about 35 lipid molecules with an apparent dissociation constant of less than 0.1 pM for the enzyme on anionic vesicles compared to 10 mM on zwitterionic vesicles. Results at hand also show that aggregation or acylation of the protein is not required for the high affinity binding or catalytic interaction at the interface. PMID- 1866430 TI - Hexamers of subunit II from Limulus hemocyanin (a 48-mer) have the same quaternary structure as whole Panulirus hemocyanin molecules. AB - Hemocyanins are copper-containing proteins that transport oxygen in a variety of invertebrates. Considerable evidence has accumulated that arthropodan hemocyanins are multimers of a fundamental hexameric unit. X-Ray crystallographic structure determination has revealed that the hemocyanin molecule from the spiny lobster Panulirus interruptus is a single hexamer having 32 point group symmetry. Using crystals of subunit II, one of 8 polypeptide types comprising the octahexameric hemocyanin of the horseshoe crab Limulus polyphemus, and the molecular replacement method for crystallographic phase determination we show that subunit II forms assemblies with the same hexameric quaternary structure as the whole Panulirus hemocyanin molecule. Observation of the same hexameric motif in two widely separated species provides strong additional evidence that this quaternary structural unit is a universal building block of arthropodan hemocyanins. PMID- 1866432 TI - Energetic approach to the folding of alpha/beta barrels. AB - The folding of a polypeptide into a parallel (alpha/beta)8 barrel (which is also called a circularly permuted beta 8 alpha 8 barrel) has been investigated in terms of energy minimization. According to the arrangement of hydrogen bonds between two neighboring beta-strands of the central barrel therein, such an alpha/beta barrel structure can be folded into six different types: (1) left tilted, left-handed crossover; (2) left-tilted, right-handed crossover; (3) nontilted, left-handed crossover; (4) nontilted, right-handed crossover; (5) right-tilted, left-handed crossover; and (6) right-tilted, right-handed crossover. Here "tilt" refers to the orientational relation of the beta-strands to the axis of the central beta-barrel, and "crossover" to the beta alpha beta folding connection feature of the parallel beta-barrel. It has been found that the right-tilted, right-handed crossover alpha/beta barrel possesses much lower energy than the other five types of alpha/beta barrels, elucidating why the observed alpha/beta barrels in proteins always assume the form of right tilt and right-handed crossover connection. As observed, the beta-strands in the energy minimized right-tilted, right-handed crossover (alpha/beta)8-barrel are of strong right-handed twist. The value of root-mean-square fits also indicates that the central barrel contained in the lowest energy (alpha/beta)8 structure thus found coincides very well with the observed 8-stranded parallel beta-barrel in triose phosphate isomerase (TIM). Furthermore, an energetic analysis has been made demonstrating why the right-tilt, right-handed crossover barrel is the most stable structure. Our calculations and analysis support the principle that it is possible to account for the main features of frequently occurring folding patterns in proteins by means of conformational energy calculations even for very complicated structures such as (alpha/beta)8 barrels. PMID- 1866431 TI - Thiol protease-like active site found in the enzyme dienelactone hydrolase: localization using biochemical, genetic, and structural tools. AB - The active site of dienelactone hydrolase (DLH), a microbial enzyme of the beta ketoadipate pathway, has been conclusively located using a combination of crystallographic, biochemical, and genetic techniques. DLH hydrolyzes a dienelactone to maleylacetate and has esterase activity on p-nitrophenyl acetate and trans-cinnamoyl imidazole. The identification of Cys-123 as containing the essential thiol confirms the localization of the active site as suggested by the crystal structure of DLH, and disproves an earlier hypothesis regarding its location. Two mutant proteins have been engineered in which Cys-123 has been converted to a serine (C123S DLH) and an alanine (C123A DLH), respectively. C123S DLH (Km = 9900 +/- 2300 microM; Vmax = 4.4 +/- 0.8 mumol/min-mg) displays burst kinetics with p-nitrophenyl acetate and is 10% as active as DLH (Km = 170 +/- 7 microM; Vmax = 21.1 +/- 0.4 mumol/min-mg). C123A DLH is inactive. The structures of DLH, C123S DLH, and C123A DLH have been refined at 1.8, 2.2, and 2.0 A, respectively. Comparison of the structures of these proteins demonstrates that the only differences between them are centered at residue 123. The structures of the active sites of DLH, papain, and subtilisin are similar and are suggestive of the three enzymes having evolved convergently to similar active sites with similar enzymic mechanisms. PMID- 1866433 TI - [On schizophrenic cases which present neurosis-like symptoms from early childhood -in relation to the prodromal signs and childhood schizophrenia]. AB - The concept of "childhood schizophrenia" is ambiguous because of problems on the diagnostic level, especially in regard to symptomatology and prognosis. After studies which produced the description of "early infantile autism", childhood schizophrenia studies were even more confused. One reason for this was that there were not sufficient follow-up studies about the schizophrenia-like psychoses during occurring childhood, on the one hand, and the retrospective-anamnestic research was limited in the field of adult psychiatry, on the other hand. The author has focused on two points of view in order to discuss the problem of childhood schizophrenia. One is the non outbreak of childhood psychoses in children from 6 to 8 years old which was demonstrated by a couple of epidemiological research studies. The other is the concept of "Knick" (in Germany) which usually accompanies classical German theories of schizophrenia. "Knick" means that, at some point in the patient's history, there is an incident that is the indication of the onset of schizophrenia. The subjects were selected from the author's own cases. They continuously and insidiously developed schizophrenic symptoms during pre-puberty and puberty, presenting behavioral abnormalities or neurosis-like signs from early childhood. The diagnostic criteria for schizophrenia corresponds to DSM-III and with the German theory of Bleuler and Schneider. All cases have been treated for more than ten years. The acute onset cases, the mentally retarded cases (DSM-III .318) and the cases with suspected organic brain disorders were excluded because of the diagnostic problems. The author could differentiate these subjects into three groups based on the development in the infantile stage. The first was autistic group and the second mentally subnormal (DSM-III .317) or borderline group. Psychiatric problems of these two groups were already obvious in early childhood. The third group developed normally until they were 3-5 years old. After that they presented neurotic symptoms having some kind of intra-familiar problems. The author could confirm that these three groups manifested various kinds of neurosis-like symptoms, mainly obsessive-compulsive ones, from 3-5 years old. The so-called latent time, which is thought to be a non-outbreak time of childhood psychoses, may correspond to the prodromal stage of schizophrenia in these cases. This research is based on study of 31 children. An in-depth study has been done by the author of 6 of these children, 2 in each of the 3 categories described above. The "Knick"-points were not identifiable in these cases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1866434 TI - [Short-term and long-term prognosis of alcohol dependence: a follow-up study of Danshu-Kai (Alcohol Abstinence Club) members]. AB - 595 alcohol dependent cases had been enrolled in the Mie Danshu-Shinsei-Kai (The Alcohol Abstinence Club in Mie) since its establishment in Jan. 1972 by Oct. 1984 when this study started. 163 cases of them, who had been practising abstinence at least for 6 months when the first observation was made in Oct. 1984, were selected for the follow-up study. Relapses in these cases were checked twice, 2.5 years later in 1987 and 5 years later in 1989. The results obtained were summarized as follows: It was observed that 64% of those who had practised abstinence for 2 years sustained abstinence successfully at least for the next 5 years, and 74% of those who had kept non-drinking for 3 years continued abstinence for the next 5 years. Those who had practised abstinence for shorter than 2 years just before the first observation showed that the closer the term of abstinence approached to 2 years, the more sharply the following 5 year abstinence rate increased. It was noticed among those who had kept abstinence for longer than 3 years that the longer the abstinence period became, the more slowly the next 5 year abstinence rate increased, eventually reaching to as high as 81%. A turning point from sharp increase to slow increase was found in between 2 and 3 years of abstinence. From the observation mentioned above, the period of abstinence can be classified into three categories in view of prognosis: shorter than 2 years, 2 to 3 years, and longer than 3 years, which stand for "unstable," "intermediate," and "stable" period respectively. The intermediate period is considered to be critically important in terms of prognosis and treatment of alcohol dependence. It would be reasonable therefore to prospect prognosis in the short term or in the long term basis according to the period of abstinence. The object and contents of treatment might become different before and after the intermediate period. The major factors which affect the prognosis can be classified into 5 categories; 1) the degree of insight into his or her drinking, 2) biological condition, 3) financial problems like "debt," 4) tendency toward multiple addiction, and 5) problems of "co-dependency." It was noticed that although all of these factors remained unresolved in most cases of unstable period, factors 1), 2) and 3) were mostly successfully resolved in a stable period. Factors 4) and 5) are found in not rarely even in a stable period.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1866435 TI - [A case of premenstrual syndrome with anovulatory menstruation after parturition which responded favorably to clomiphene-HCG therapy]. PMID- 1866436 TI - Emotional profiles of families with a heart-operated patient: a pilot study. AB - Family interaction is a basic factor in determining the quality of life of patients undergoing heart surgery. The present study investigates the emotional attitudes in the relatives of 10 heart-operated patients. The results indicate that a high amount of relatives' emotional overinvolvement and warmth tends toward a correlation with lower anxiety and depression scores, and with a better 12-month outcome of the illness. PMID- 1866437 TI - Depression and allergies: survey of a nonclinical population. AB - The possible association between depression and type I allergies (i.e. immunoglobulin E-mediated hay fever, asthma, eczema, hives) was examined in a nonclinical sample of 379 college students. Measures included self-reports of depression, tiredness, fearfulness, allergic disorders, and environmental allergens and irritants. Seventy-one percent of the subjects who had ever received a professional diagnosis of depression also indicated a history of allergy: those with greater self-rated current depression overall reported a significantly higher prevalence of asthma (p less than 0.05). Type I allergic (43%) and nonallergic subjects did not differ in self-rated frequency of depression, fatigue, or anxiety. However, type I subjects reported significantly worse mood after the flu than did nonallergic subjects (p less than 0.001). The data support the hypothesis that individuals prone to clinical depression have more allergies than nondepressives. Allergics may experience more postflu mood worsening but not current depression in comparison with nonallergics. PMID- 1866438 TI - Comparative neurobiological and neuropsychological deficits in adolescent and adult schizophrenic and nonschizophrenic patients. AB - A group of 24 adolescents and young adults were classified according to four measures using Research Diagnostic Criteria on the dimension of the severity of their schizophrenic syndrome. Independent assessments by the Gottschalk-Gleser Social Alienation-Personal Disorganization Scale and the Abrams-Taylor Emotional Blunting Scale corroborated that the definite schizophrenic group (n = 7) was significantly more schizophrenic than the not schizophrenic group (n = 12), but not more so than the probably schizophrenic group (n = 5). The Halstead-Reitan Category Test and Rhythm Test significantly differentiated the definite schizophrenic group from the not schizophrenic group with respect to cognitive impairment. The Gottschalk-Gleser Cognitive Impairment Scale did not indicate a significant difference in cognitive function between these patient groups. The computerized EEG revealed a significantly higher percent of EEG abnormalities among the definite and probably schizophrenic groups than the not schizophrenic group of patients. These findings are analyzed and discussed. PMID- 1866439 TI - Specificity revisited and updated. AB - Typicality is probably a better representation of Alexander, Dunbar and others' conclusions than specificity, which was always too absolute a term. As such it became a valid cause of objection by opponents. No genuine attempts to repeat the original studies have been made and most of the original opposition to the concept is now acknowledged as invalid. Typicality (specificity) in psychosomatic disorders appears to be conferred by coping mechanisms acquired through interaction with mother and early surrogates in infancy and childhood as a means of reducing tensions and restoration of homeostatic emotional equilibrium. Psychosomatic medicine patients share one such mechanism, notably superstability/alexythymia, but contained within it are coping mechanisms typical for differing disorders. Examples are listed, and also mention of typicality of recurrently provocative life events/situations. Until typicality is appreciated, taught, learned and practised, success in management of psychosomatic disorders will be limited. The current bio-psycho-social approach is too imprecise. PMID- 1866440 TI - Patterns of self-definition of asthma patients and normal persons in the Freiburg Personality Inventory. AB - The concept of the specificity of psychosomatic diseases (Alexander) is being differentiated at the time. In order to clarify some aspects of this problem, we want to investigate whether types of self-rating of normal persons differ from those of patients with bronchial asthma. In a second step we shall examine whether those types of self-rating can be found also in expert rating and third the differences between the two groups concerning their help-seeking behavior. For the purpose of this investigation the data of 135 patients with bronchial asthma (who had been investigated at the Heidelberg University Medical Department between 1979 and 1982) and of 330 persons of the Mannheim Cohort Study (who are a representative sample of the average urban population) have been reanalyzed. By means of the Freiburg Personality Inventory (FPI) data cluster analyses have been done. Evaluated by a group of 5 (5-cluster solution) the patterns of self-rating of patients with bronchial asthma do not differ significantly from those of normal persons. They had a high correlation to the expert rating and to other social-medically important outer criteria. The results indicate that the specificity of psychosomatic patients in relation to normal persons is not very convincing in a pattern of self-rating on the level of the FPI. Therefore, further research in this field seems to be necessary. PMID- 1866441 TI - Psychotherapeutic treatments evaluated with two instruments: clinical questionnaire and semantic differential. AB - We evaluated about 100 psychotherapeutic treatments on the Freudian model with two independent instruments: a clinical questionnaire (assessed globally and intuitively) and a semantic differential (processed through various mathematic analyses). The results obtained with the two instruments were compared, and we also compared the semantic evolution of patients with that of normal subjects. Both instruments show an undeniable average improvement among patients. The semantic differential also shows that the various 'zones' tested by the inducive words are neither equally affected by neurosis nor equally modified by treatment. PMID- 1866442 TI - Role of the forebrain in nociception. PMID- 1866443 TI - Role of the forebrain in sensation and behavior. Proceedings of a symposium. Moffett Field, California, May 26-27, 1989. PMID- 1866444 TI - "Perestroika" in the basal forebrain: opening the border between neurology and psychiatry. PMID- 1866445 TI - Local circuitry of the somatosensory thalamus in the processing of sensory information. PMID- 1866446 TI - Contributions of the amygdalar complex to behavior in macaque monkeys. PMID- 1866447 TI - Biochemical switching in hypothalamic circuits mediating responses to stress. PMID- 1866448 TI - Neural mechanisms underlying corticospinal and rubrospinal control of limb movements. PMID- 1866449 TI - Forebrain nuclei involved in autonomic control. AB - Several key regions of the forebrain are involved in regulation of autonomic functions. These areas include the several areas within the hypothalamus (viz., paraventricular hypothalamic nucleus, lateral hypothalamic area, posterior periventricular area, and zona incerta), the basal forebrain (viz., central nucleus of the amygdala and bed nucleus of the stria terminalis), and the cerebral cortex (viz., insular and medial prefrontal cortex). All these areas have been implicated on anatomical grounds to be part of a central autonomic network involving multiple interconnecting circuits. Apart from these complex interconnections, most of these areas project to the lower brain stem where they are capable of influencing the cell groups which innervate the vagal and sympathetic preganglionic neurons or in some cases, like the paraventricular hypothalamic nucleus and the lateral hypothalamic area, provide direct projections to these neurons. PMID- 1866450 TI - [Properties of intracellular Ca store and its Ca release mechanisms in smooth muscle cells]. PMID- 1866451 TI - [Cytokines as inflammatory mediator]. PMID- 1866452 TI - [Determination of the primary structures of proteins by mass spectrometry]. PMID- 1866454 TI - [Progress on the plan for human genome project in Japan]. PMID- 1866453 TI - [Molecular organization of photosystem I reaction center]. PMID- 1866455 TI - [Function of ets proteins: gene regulation coupled with signal transduction]. PMID- 1866456 TI - A unified account of the effects of distinctiveness, inversion, and race in face recognition. AB - A framework is outlined in which individual faces are assumed to be encoded as a point in a multidimensional space, defined by dimensions that serve to discriminate faces. It is proposed that such a framework can account for the effects of distinctiveness, inversion, and race on recognition of faces. Two specific models within this framework are identified: a norm-based coding model, in which faces are encoded as vectors from a population norm or prototype, and a purely exemplar-based model. Both models make similar predictions, albeit in different ways, concerning the interactions between the effects of distinctiveness, inversion and race. These predictions were supported in five experiments in which photographs of faces served as stimuli. The norm-based coding version and the exemplar-based version of the framework cannot be distinguished on the basis of the experiments reported, but it is argued that a multidimensional space provides a useful heuristic framework to investigate recognition of faces. Finally, the relationship between the specific models is considered and an implementation in terms of parallel distributed processing is briefly discussed. PMID- 1866457 TI - The coordination of bimanual aiming movements: evidence for progressive desynchronization. AB - It is known that when simultaneous bimanual aiming movements are made to targets with different IDs (Index of Difficulty), Fitts' Law is violated. There is massive slowing of the easy target hand, but a debate has arisen over the degree of synchronization between the hands and whether this effect represents a coordinative structure or interference due to neural cross-talk. This issue was investigated in an experiment with 12 subjects who moved styli forward in the sagittal plane to pairs of targets that differed in difficulty (0.77/3.73 ID and 0.77/5.17 ID). Reaction time, movement time, and kinematic measures of resultant velocity and acceleration were analysed. The results showed clear-cut timing differences between the hands that depended on both the ID difference between target pairs and elapsed time of the movement. The violation of Fitts' Law was confined to the easy target hand. Pronounced individual differences in both timing differences and left-right asymmetry were also noted. Neither the coordinative structure nor the neural cross-talk models can fully account for these data, and it is possible that the initial constraints on movement are moderated by visually driven corrective movements. PMID- 1866458 TI - A study of the effect of structural information and familiarity in form perception. AB - Two experiments were carried out to investigate the influence of structural information and familiarity on the processing of visual forms. Pairs of "well" structured and nameable and "poorly" structured and non-nameable fragmented forms were employed as stimuli. The effects of structure and familiarity were assessed by manipulating the visual hemifield of presentation and the task. In Experiment 1 stimuli were judged as being either in the same orientation or mirror-reversed, a task that does not require high-level semantic information to be processed. Experiment 2 required physically identical forms to be matched, which may use either physical or name information. In Experiment 1 "same" judgements were equivalent for both types of stimuli, and "different" judgements were longer for the "poorly" structured (non-nameable) forms. In Experiment 2 there was little overall difference between "well" and "poorly" structured forms, though response times to "well" structured (nameable) forms were slowed for right-visual-field presentations. It is suggested that familiarity may not be sufficient to provide a perceptual advantage for nameable forms, as the advantage for nameable stimuli was confined to "same" judgements in Experiment 1 and response times were shorter for non-nameable stimuli in Experiment 2. Rather, performance depends upon factors such as the computation of global shape (due to structural properties of collinearity and closure) and on the use of different kinds or representations (physical versus name) in matching. PMID- 1866460 TI - Prosopagnosia: a reclassification. AB - We report a quantitative investigation of three patients who presented with a profound prosopagnosia. They were tested on a series of tests of face perception, face recognition, and paired associate learning using faces. A patient with marked perceptual difficulties but no difficulty whatever in recognizing faces was tested as a control. The control patient's performance was as bad or worse on the tests of perception of faces, and it is concluded that impaired performance on tests of face perception does not contribute to difficulties in recognizing familiar faces. The major difference between the three prosopagnosic patients was the evidence of covert recognition in two of these cases but not in the third. We use this evidence to argue that the perceptual/mnestic distinction is an inappropriate classification and would suggest instead that the two types may be described in terms either of a disconnection of the face recognition units or of damage to the units themselves. PMID- 1866459 TI - Distinguishing representation deficits and processing deficits in a case of acquired dysgraphia. AB - The same acquired disorder of spelling may be due to deficits affecting lexical representations of word spelling or deficits affecting the mechanisms that process those representations. This study sought to distinguish these possibilities in a dysgraphic patient. The integrity of the patient's lexical orthographic representations was assessed by having him decide whether or not pairs of words presented auditorily rhymed. Although the patient was impaired on a variety of spelling tasks and with all types of stimulus material, he showed a normal effect of spelling on the rhyme task. Like normal subjects, he was faster at deciding that words rhymed when they were spelled similarly (e.g. tool-cool) than when they were spelled dissimilarly (e.g. rule-cool) and slower at deciding that words did not rhyme when they were spelled similarly (e.g. toad-broad) than when they were spelled dissimilarly (e.g. code-broad). Therefore, as the patient's lexical representations of word spelling seemed to be generally intact, his spelling problems were probably due to difficulty in processing those representations. PMID- 1866461 TI - Object-centred inhibition of return of visual attention. AB - Our response to visual events can be delayed at positions we have recently examined attentively. Such inhibition could organize visual search through static scenes by suppressing those loci already searched, but this mechanism would fail in moving scenes as objects' locations then change during search. We cued attention to a moving object and found subsequent inhibition at the locus the object later occupied. This implies that previously examined objects are suppressed. Such object-centred inhibition would be highly adaptive, but would require a sophisticated neural implementation for a mechanism held to be sub cortical. PMID- 1866462 TI - Stage I-II squamous cell carcinoma of the oral cavity treated by iridium-192: is elective neck dissection indicated? AB - This is a retrospective analysis of 233 evaluable patients with stage I-II squamous cell carcinoma of the oral cavity treated by definitive branchytherapy. Minimum follow-up is 3 years. Treatment of neck was chosen by a multidisciplinary team, according to age, medical status and availability for regular follow-up. One hundred and ten patients (47%) underwent elective neck dissection (END); 28 (25%) had positive nodes and received neck irradiation post-operatively. One hundred and twenty three patients (53%) were regularly followed up only, with therapeutic neck dissection (TND) reserved for cases of node relapses. In the END group, there were 19 neck relapses (17%): 12/60 (20%) in patients with mobile tongue carcinoma and 7/50 (14%) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 9/19 (47%) cases. In the TND group, there were 21 neck relapses (17%): 16/82 (20%) in patients with mobile tongue carcinoma and 5/41 (10%) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 13/21 (62%) cases. Ten-year survival is 37% for the END group and 31% for the TND group. Tumour stage and infiltration into underlying tissues increased the probability of neck relapse and death. Furthermore, a multivariate analysis showed that patients treated in the TND group had a higher probability of death than patients treated in the END group (p less than 0.04). PMID- 1866463 TI - Radiation therapy in extrahepatic bile duct carcinoma. AB - Fifty-one patients with carcinoma of the extrahepatic bile ducts (EHBD) received radiation therapy between January 1980 and December 1988. The location of the tumors was: proximal third, 20 patients; middle third, 23 patients; distal third, 3; diffuse, 5 patients. Thirty-six patients underwent surgery with complete gross resection in 14 (10/14 with positive margins), incomplete gross resection in 12 and only biopsy in 10. Fifteen patients had only biliary drainage without laparotomy after cytologic diagnosis of malignancy in 11/15. Radiation therapy was done with curative intent after complete or incomplete resection (n = 26) and it was palliative in patients who had no resection or only biliary drainage (n = 25). Twenty-five patients received external radiation-therapy (ERT) alone to the tumor and lymph nodes (mean dose 45 Gy/2 Gy per fraction for cure, 35 Gy/10 fractions for palliation), 8 patients had only iridium-192 (192Ir) implant (50-60 Gy at a 1 cm radius for cure, 30 Gy for palliation), 17 patients had both ERT + 192Ir (ERT 42.5 Gy + 192Ir 10-15 Gy for cure; ERT 20 Gy/5 fractions + 192Ir 20-30 Gy for palliation) and one intra-operative irradiation + ERT. The overall survival for the entire group was 55, 28.5 and 15% at 12, 24, 36 months and median survival 12 months. Median survival was 22 months in patients treated with curative intent and only 10 months after palliative treatment (p 0.03). Among patients who had curative treatment, median survival was 27.5 months after complete gross resection and 13 months after incomplete gross resection (p 0.045).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866464 TI - Total perturbation correction factor for PTW and NACP plane parallel chambers in electron beams. AB - The international protocols of electron dosimetry published by the Nordic Association of Clinical Physics and the Sociedad Espanola de Fisica Medica recommend the use of a total perturbation correction factor pu, pp which is constant for all plane parallel chambers. In this work we have compared the dose measured with the PTW-Markus and NACP plane parallel chambers in respect to a cylindrical one. The obtained results indicate that for the ionization chamber NACP the value of pu, pp = 1.000 +/- 0.005 is adequate while for the ionization chamber PTW the observed difference is explained by considering an individual total perturbation correction factor variable with the mean energy at depth z, Ez, as the fluence perturbation correction factor pf is usually given for cylindrical chambers. PMID- 1866465 TI - Preoperative irradiation for tethered rectal carcinoma. AB - Twenty-eight patients with resectable but tethered rectal carcinomas were treated with preoperative irradiation (EBRT) and surgical resection. The 5-year actuarial disease-free survival and local control rates of these 28 patients were 66 and 76%, respectively. Two patients have developed local failure only, 2 patients concurrent local failures and distant metastases, and 4 patients distant metastases only. All local failures occurred in areas of tumor adherence to unresectable structures (sacrum, pelvic side wall). Patients with tethered rectal tumors are at risk for local failure despite preoperative irradiation and surgical resection. To improve local control in this subset of patients, an intraoperative radiation therapy (IORT) boost is given to areas of tumor adherence at resection following EBRT. PMID- 1866467 TI - The need for prospective clinical studies in thymomas. PMID- 1866466 TI - LQ and time model. PMID- 1866468 TI - Post-operative radiotherapy in invasive thymoma. AB - The experience of a large Cancer Institute in treating invasive thymoma has been reviewed. Twenty-eight patients received radiotherapy following biopsy or incomplete resection of a thymoma. The overall survival was 53% at 5 years and 44% at 10 years. Treatment was generally well tolerated but three patients (11%) developed significant side effects from the radiotherapy and two of these died. Radiotherapy appeared to be more effective in patients who had a small volume of residual disease after surgery. An attempt was made to identify prognostic factors but none reached statistical significance. The radiation dose, field size and the use of systemic treatment are discussed. PMID- 1866469 TI - A radiotherapeutic experience for localized extranodal non-Hodgkin's lymphoma: prognostic factors and re-evaluation of treatment modality. AB - Between 1966 and 1988, 149 patients were treated with radiotherapy for localized extranodal lymphoma. The average total dose given was 39.8 Gy for low grade disease and 48.7 Gy for all other disease. Of the 149 patients, 60 also received adjuvant chemotherapy. Twenty-four had low grade lymphoma, 109 had intermediate grade disease, and 16 had high grade disease, histologically. The distribution of histological grade and T/B phenotype varied with the primary site. Low grade lymphomas were found mainly in the orbit, and T-cell lymphomas were found in the nasal cavity and nasopharynx. The 5-year survival rates according to tumor location were 89% for oral cavity, 86% for paranasal sinus, 83% for thyroid, 69% for orbit, 47% for Waldeyer's ring (WAR), 44% for testis, 23% for CNS, 21% for nasal cavity and 60% for other sites. Histological grade and T/B phenotype both had prognostic importance. Combined chemotherapy significantly improved the survival rate only for disease with intermediate or high grade histology. Other prognostic factors according to the primary site were the bulk of lymph node for WAR disease, the radiation dose for CNS disease, bone erosion for orbital disease, stridor for disease of the thyroid, and the tumor stage for disease of both the testis and the thyroid. PMID- 1866470 TI - The curability of tumours of differing size by targeted radiotherapy using 131I or 90Y. AB - A mathematical model has been used to investigate the relationship of curability to tumour size and cell number for spherical tumours treated with targeted 131I or 90Y, assuming uniform uptake of radionuclide throughout the tumour. The analysis shows that, for any given cumulated activity per unit mass of tumour, cure probability is greatest for tumours whose diameter is close to an optimum value which depends on the path length of the emitted beta-particle. Smaller tumours are less curable because of inefficient absorption of radiation energy, and larger tumours are less curable because of greater clonogenic cell number. The lesser curability of very small tumours is a feature of targeted radiotherapy using long-range beta-emitters which does not occur with external beam irradiation. The predicted inefficiency of sterilisation of microscopic tumours poses a problem for targeted radiotherapy which is analogous to "geographic miss" in conventional radiotherapy. The implication is that small micro-metastases could escape sterilisation by radionuclides administered at activity levels sufficient to eradicate larger tumours. It is suggested that single agent targeted radiotherapy should not be used for treatment of disseminated malignancy when multiple tumours of differing size, including micrometastases, may be present. The analysis implies that an advantage might result from the use of a panel of several radionuclides (including short-range emitters) or from combining targeted radiotherapy using long-range beta-emitters with external beam irradiation or some other modality to which microscopic tumours are preferentially vulnerable. PMID- 1866471 TI - Endothelin as a putative sensory neuropeptide in the guinea-pig: different properties in comparison with calcitonin gene-related peptide. AB - Both endothelin-(ET) and calcitonin gene-related peptide- (CGRP) like immunoreactivity (-LI) were present in a variety of organs and neuronal tissue of the guinea-pig as determined by radioimmunoassay (RIA). Neuronal tissues like dorsal root ganglia (DRG) contained by far the highest levels of both ET- (65 +/- 11 pmol/g) and CGRP-LI (34 +/- 5 pmol/g). The tissue levels of ET-LI remained unchanged after 6-hydroxydopamine and capsaicin-pretreatment, while CGRP-LI was markedly reduced after capsaicin. Chromatographic characterization revealed that the main portion of ET-LI in the DRG, right atrium and lung corresponded to synthetic ET-1. Immunohistochemical studies showed the presence of ET-LI in a few neurons of intact DRG and many neurons in DRG cell-cultures, partly co-existing with CGRP-LI. In the neuronal cells of DRG cultures the ratio between the ET- and CGRP-LI was 1:27 compared to 2:1 in intact DRG. 24 h after ligation of the sciatic or vagal nerves no accumulation of ET-LI was observed above the ligation, while CGRP-LI was increased 4-5-fold. Transection (10 days) of the sciatic nerve caused a 85-95% depletion of CGRP-LI in the distal skin, gastrocnemius muscle and trunk below the transection site, while in the proximal portion of the nerve CGRP LI increased. No effects on ET-LI in these tissues were observed after sciatic nerve transfection. In release experiments on DRG cell cultures. Langendorff heart preparations or perfused guinea-pig lungs, potassium (60 mM), capsaicin or antidromic nerve stimulation evoked a clear-cut increase in the supernatant levels of CGRP-LI, suggesting release, while no effect on the ET-LI concentration was observed in the effluent. Furthermore, anoxia failed to influence the outflow of ET-LI from the heart and lung. It is concluded that ET-1-LI is present in high levels in spinal ganglia and ET-LI occurs in afferent cell-bodies, but in comparison with CGRP, ET shows remarkable inertness upon various experimental conditions including no evidence for axonal transport, loss after denervation or release. The neuronal ET-LI seems to increase under culture conditions, however. The possible function for the high content of ET-LI in the intact guinea-pig peripheral nervous system remains to be elucidated and may mainly be related to a non-neuronal pool considering the relatively low content of ET-LI compared to CGRP in cultured DRG cells. PMID- 1866472 TI - Increased plasma levels of neuropeptide Y-like immunoreactivity and catecholamines in severe hypertension remain after treatment to normotension in man. AB - Circulating levels of neuropeptide Y (NPY)-like immunoreactivity (-LI), adrenaline and noradrenaline (NA) were analysed in 17 patients admitted to the emergency ward due to severe hypertension; blood pressure mean 204/127 mmHg. The levels of NPY-LI and NA were significantly higher (P less than 0.001) in the hypertensives as compared to a normotensive control group. HPLC analysis revealed that the plasma contained besides NPY-LI also several NPY-LI fragments of low hydrophobicity. Following 2 to 3 weeks treatment the blood pressure had decreased to a mean of 150/89 mmHg. However, circulating levels of NPY-LI (P less than 0.001) and NA (P less than 0.01) were still significantly higher than in controls in spite of the marked reduction in blood pressure. Simultaneous measurements of adrenaline did not reveal any significant changes and these values did not differ compared with those in the normotensive subjects. The findings suggest that peripheral markers of the sympathetic system (NPY-LI and NA) in severe hypertension is not directly related to the blood pressure level. PMID- 1866473 TI - Diagnostic relevance of the amino-terminal cleavage peptide of procalcitonin (PAS 57), calcitonin and calcitonin gene-related peptide in medullary thyroid carcinoma patients. AB - We have identified the amino-terminal cleavage peptide of procalcitonin (PAS-57) in the plasma of normal human subjects and of medullary thyroid carcinoma (MTC) patients together with calcitonin (CT) and CT gene-related peptide (CGRP). Major components on reversed-phase high-pressure liquid chromatography had the retention times of synthetic PAS-57, CT and CGRP as well as of precursor proteins. Plasma levels of PAS-57 (290 +/- 50 pgeq/ml; mean +/- S.E.M.), CT (27 +/- 8 pgeq/ml) and CGRP (8.4 +/- 0.8 pgeq/ml) were respectively 2.3-, 1.6- and 1.5-fold higher in normal men (n = 10) than in women (n = 8). In response to 1 min intravenous calcium infusions (2 mg per kilogram body weight) PAS-57 and CT were increased 3.5- and 2.7-fold (P less than 0.001), respectively, but CGRP remained unchanged. In MTC patients (n = 57) with raised levels of PAS-57 and CT, the molar ratio between PAS-57 and CT was 1.7-times higher than in normal subjects (P less than 0.01). We have found that PAS-57 is a predominant CT/CGRP gene derived product in the circulation of normal subjects and of MTC patients and a potential new MTC tumor marker. PMID- 1866474 TI - CCK stimulates growth of six human pancreatic cancer cell lines in serum-free medium. AB - The growth responses of six human pancreatic cancer cell lines (SW-1990, PANC-1, MIA PaCa-2, BxPC-3, RWP-2 and CAPAN-2) to cholecystokinin (CCK) were evaluated in serum-free medium (SFM). In each experiment cells were initially plated in media containing fetal calf serum (FCS) grown for 48-72 h, and then washed with saline. Cells were incubated for an additional 72 to 96 h in medium devoid of FCS in the absence (control) or presence of synthetic CCK analogue (Thr4,Nle7)CCK9 (10(-13) to 10(-9) M), or CCK8 (10(-12) to 10(-9) M), or CCK39 (10(-12) to 10(-9) M). Viable cell counts were performed with a hemocytometer. Growth of each cell line was stimulated in the presence of CCK in serum-free medium, although the magnitude of responses differed. The concentrations of (Thr4,Nle7)CCK9 which stimulated the greatest increase in cell counts as compared to controls for each cell line were: SW-1990, 39% (10(-12) M, P less than 0.05); PANC-1, 45% (10(-9) M, P less than 0.005); MIA PaCa-2, 42% (10(-12) M, P less than 0.005); BxPC-3, 32% (10(-13) M, P less than 0.05); RWP-2, 37% (10(-11) M, P less than 0.005). Maximal response to CCK8 occurred at the 10(-9) M dose for each cell line: MIA PaCa-2, 40% (P less than 0.025); PANC-1, 85% (P less than 0.001); RWP-2, 68% (P less than 0.001) and CAPAN-2, 52% (P less than 0.001). The maximal increase in cell count with CCK39 ranged from 44-74% and occurred with either 10(-11) or 10( 10) M. CCK8 in SFM also stimulated cell growth as well as or better than FCS alone in three out of four pancreatic cell lines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866475 TI - [Intrathecal opiate-spinal anesthesia. Clinical results of a 1-year study using 0.0375-0.15 mg morphine]. AB - In a prospective study, 184 patients were studied after orthopedic operations with regard to analgesic requirements, analgesic effectiveness, and appearance of postoperative complications. In four groups, 0.0375, 0.075, 0.1 or 0.15 mg morphine was given in combination with 0.5% hyperbaric bupivacaine for perioperative analgesia. The patients' ages ranged between 13 and 90 years (means = 62.97). One hundred sixteen patients did not need any analgesics in the first 24 h. The effect of the spinal opiate was found to be pleasant, especially by patients who received a total hip prosthesis: in this group the average duration of analgesia was more than 24 h in 77.9% and 14.5 h in 22.1% of patients. The need for additional postoperative analgesia was seen earliest in the patients who received a knee prosthesis of the sledge type (P less than 0.05). The overall consumption of the analgesic piritramid was clearly reduced and amounted to 7.7 mg on the day of operation, 8.4 mg on the 1st day, 6.0 mg on the 2nd day, and 3.6 mg on the 3rd day after surgery. The degree of postoperative analgesia was the same in all four groups (P greater than 0.05). Blood gas analyses, respiratory rate, blood pressure, heart rate, oxygen saturation, and laboratory parameters were also examined. The application of small doses of opiate close to the spinal cord produced a good and long-lasting reduction of pain with few opiate side effects. In the spinal anesthetics with larger doses of morphine, side effects were rare and hardly different from those accompanying spinal anesthesia without morphine addition. There were no serious complications noted during the opiate anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866476 TI - [Pharmacokinetics of articaine in mandibular nerve block]. AB - Up to now, mandibular nerve blocks have been carried out without knowing the exact blood concentrations resulting from the use of the local anesthetics. Due to the high vascularity a rapid increase in serum local anesthetic levels is to be expected. Due to analytical problems, the literature provides controversial statements about the pharmacokinetics of articaine which is generally used for this block. The given half-life periods following intramuscular application range from 39 min [8] to 31 h [6]. For this reason, mandibular nerve blocks with 2 ml 4% articaine with 1:200,000 epinephrine were carried out in 10 awake patients and 10 patients during intubation anesthesia. RESULTS. Blood samples from peripheral veins showed an average maximum concentration of 2.1 +/- 1.3 mg/l after 12.5 +/- 2.5 min. After 8 h the value had fallen below the minimum detection limit of 0.05 mg/l. In the present study, a half-life of approximately 20 min was determined for articaine after conduction anesthesia. This local anesthetic holds an exceptional position because as an amide-type local anesthetic it contains an additional ester group that is hydrolytically metabolized in the blood. The concentration of the resulting metabolite reaches a maximum value of 2.6 +/- 1.6 mg/l after 40 to 50 min. CONCLUSIONS. Compared to other amide-type local anesthetics, whose terminal plasma half-life varies between 1 and 3.6 h [5], the value of 20 min found for articaine is very low. This is in part due to its structure, as the ester group is rapidly metabolized by plasma esterases. Because of its rapid breakdown articaine is very suitable for use in oral surgery. The HPLC method represents an uncomplicated analytical technique for the determination of local anesthetics levels in blood and other body fluids. PMID- 1866477 TI - [Subarachnoid placement of a peridural catheter with high spinal anesthesia. The advantage of 0.25 % bupivacaine]. AB - A 72-year-old female patient was scheduled for abdominal surgery with epidural block in combination with general anesthesia. An 18 G epidural catheter was inserted through an 18 G Tuohy needle between T12 and L1 using the midline approach and the 'loss of resistance' technique. A test dose of 13 ml bupivacaine 0.25% showed no effect and a bolus of 12 ml bupivacaine 0.25% was added 8 min later. Bilateral analgesia between S5 and C4 developed over the following 17 min but was not accompanied by any cardiovascular or respiratory depression. The patient became sleepy and was finally intubated after the administration of thiopentone 175 mg and pancuronium 6 mg. There were no objections to surgery, so the hemicolectomy was continued as planned. Intraoperatively the systolic blood pressure dropped twice, to a minimum of 105 mm Hg, coinciding with eventration of the intestine, but this was reversed immediately on administration of a vasoconstrictor. Extubation of the patient was possible 90 min later on the termination of surgery, when the level of anesthesia had reached T2. A spinal X ray with radiopaque dye showed a typical intrathecal distribution. Most remarkable in this case is the stability of the cardiovascular function which in our opinion is related to the 0.25% solution. Serious complications of an inadvertent dural puncture can be avoided or alleviated with this concentration if the epidural block is to be combined with general anesthesia. PMID- 1866478 TI - [Adequacy of homemaker services in Gironde according to the PAQUID program]. AB - Allocation of home-help for the elderly is often unsatisfactory, because of the lack of objective assessment of the potential needs. The PAQUID project, a prospective study of 2,792 residents of the Gironde, aged 65 and over, can be used for the determination of the potential need for home-help, and its level of satisfaction in the area. The need is defined by two conditions: living alone and beeing dependent for at least one of 5 Instrumental Activities of Daily Living of the Lawton's scale. The coverage rate is 48.7% and the targetting rate is 45.2%. These rates show a high level of potential needs which are not satisfied especially in rural areas. This approach can be helpful in the planning of home services for the aged. PMID- 1866479 TI - [Evaluation of the socioeconomic costs of cutaneous leishmaniasis in French Guiana]. AB - The socio-economic cost of leishmaniasis in French Guiana was estimated using a retrospective survey spreading over a period of one year: 1979-80. The financial cost elements taken into account were the following: dermatological consultations, biological tests, treatments and hospitalisation days. Other elements were not evaluated, such as days of military hospital stays, work days suspended and unavailability of service. The cost of leishmaniasis represented 0.13% of the general budget of French Guiana and 0.43% of the global budget of the French Guiana Social Security. PMID- 1866480 TI - [Seroepidemiological study of human leptospirosis at Reunion Island]. AB - In order to evaluate the prevalence of human leptospirosis in Reunion island and to identify possible risk factors, a study was realised on a representative population sample of 3.338 persons. The prevalence of leptospirosis, diagnosed by ELISA and confirmed by Micro Agglutination Test, was 1.1%. Male predominance and higher prevalence in rainy parts of the island, were confirmed. It has not been possible to display risk factors such as housing conditions or professional exercise. The serological repartition showed not only icterohaemorrhagiae serovar, but also canicola, panama and sejroe, especially in women. These results, compared with clinical studies (showing nearly exclusive male repartition, in agricultural workers, due to icterohaemorrhagiae serovar), confirm the double look of human leptospirosis in Reunion island: clinical leptospirosis, severe, concerning males, often countrymen, due to icterohaemorrhagiae serovar, and infraclinical leptospirosis, concerning principally females, which is a domestic illness, due to other serovars. PMID- 1866481 TI - Alcohol and breast cancer in an area with high alcohol consumption. AB - The association between alcohol drinking and breast cancer risk was investigated in 132 breast cancer cases and 499 controls with acute conditions unrelated to alcohol or any of the suspected risk factors for breast cancer, in an area which shows among the highest levels of alcohol consumption and prevalence of alcohol related diseases in Europe (i.e. Pordenone Province, Northeastern part of Italy). Compared with non-drinkers, the multivariate odds ratio (OR) for ever drinkers was 1.5 (95% confidence interval, CI: 0.8-2.6). The risks for wine (the almost exclusive source of alcohol in the present investigation) were 1.2 for up to 1 drink, 1.4 for up to two drinks, 1.9 for up to 3 and 1.6 for over 3 drinks per day. Time-related factors (i.e. drinking habit duration and age at start of drinking) did not seem to be risk indicators. PMID- 1866482 TI - [Consumption of tobacco, alcohol, psychotropic drugs and illegal drugs in high school students of the department in the Upper Pyrenees]. AB - A study was conducted on a representative sample of high school students in Hautes-Pyrenees, to measure their consumption of toxics (tobacco, alcohol, psychotropic and illicit drugs) and to explore the role of selected explanatory factors. Consumption levels were high, particularly for tobacco: 45% were smoker and 4% smoked more than 15 cigarettes each day. Less than 5% were alcohol daily consumers. Technical school students are a high risk population when they are 16 years old or less. Evening out represents a risk indicator: use of toxics is more frequent for students having twice evenings out each month or more. Prevention should be global, including the adolescents concerned and adults. PMID- 1866483 TI - [The value of erythrocytic protoporphyrin measurement for screening blood donors for iron deficiency: a decision analysis]. AB - Blood donors are considered as a group with increased risk of iron deficiency. Therefore it seems particularly useful to have a simple screening test at one's disposal in blood centers to detect easily early iron deficiency. Erythrocyte protoporphyrin assay on an hematofluorometer is very easy and of a low cost. So we studied its diagnostic value on a sample of 285 blood donors (131 men and 154 women). Prevalence of iron deficiency, defined by the coexistence of, at least, two abnormal indicators (serum ferritin, transferrin saturation, erythrocyte protoporphyrin, mean corpuscular volume), was 5.6% in this sample; sensitivity of erythrocyte protoporphyrin used alone was 75% and its specificity was 91.5%. We used a decision analysis to evaluate the opportunity of screening with this test, accompanied where indicated by iron supplements. The results, though preliminary, suggest that erythrocyte protoporphyrin measurement could be of interest in screening blood donors for iron deficiency. PMID- 1866484 TI - [Logistics regression in epidemiology. II]. AB - The logistic regression is used in epidemiology to study the relationships between a disease in two modalities (diseased or disease free) and risk factors Xi which may be qualitative as quantitative variables. According to this model, the probability of disease knowing Xi's values is written: [formula: see text]. The coefficients satisfy to the equation: ORi = exp(beta i) where ORi is the odds ratio linked to the variable Xi adjusted on the other variables of the model. The second part of this paper is devoted to the tests of hypothesis in the logistic model and to the choice of the variables to be included in the model. The way of using tests to decide how to code variables is explained. Analysis strategy (choice and selection of variables) is discussed. The rational of goodness of fit tests is shown. At least, we indicate how to use the logistic model in case controls studies and in studies with matched samples. PMID- 1866485 TI - [Which controls should be chosen in a case-control study? Survey of bladder cancer in Herault]. AB - A case-control investigation about bladder cancer was carried out in Herault department with 219 incident cases from January 1987 to May 1989 and two control groups: 196 hospital controls randomized from hospital admission lists and 794 population controls randomized from census data. According to the comparison for those two groups, there are few socio-demographic differences; but hospital controls are more exposed to smoking, coffee, alcohol, artificial sweetners. So, the odds ratios with those hospital controls are under-estimated. We can evaluate the resulting biais. PMID- 1866486 TI - [AIDS: projections to the year 2000]. PMID- 1866487 TI - Translocation of alkaline phosphatase during the activation of B cells. AB - The association of alkaline phosphatase (ALPase) with the cytoskeleton in lymphoid cells was investigated. Extracting cells with non-ionic detergents such as Triton, we determined that ALPase is present in the cytoskeletal fraction in fully differentiated B lymphocytes, X63 myeloma cells and Sp2/O hybridoma cells. During the course of B-lymphocyte activation, the ALPase shifted from a soluble to a Triton-insoluble form. Changes in the phosphorylation of Triton-insoluble proteins with molecular weights of 120, 100, 90, 75, 34 and 31 kDa were detected, coinciding with the appearance of the ALPase in this fraction. The possible role of ALPase in the differentiation of B cells is discussed. PMID- 1866488 TI - [Therapeutic effectiveness of anticoagulation in acute myocardial infarction: a case-control study]. AB - The main aim was to assess the role of anticoagulant therapy (AT) in reducing the mortality for patients with acute myocardial infarction (AMI). A pair-matched case-control study was designed according to three confounding factors: gender, age (+/- 5 years), and hospitalization date (+/- 13 months). Cases were defined as patients with AMI who died during hospitalization and controls were those patients with AMI who survived. Excluded from the study were patients with strong indications or contraindications for use of AT, and also those with early death (less than 12 hr). The study undertaken at the National Institute of Cardiology "Ignacio Chavez" of Mexico City and all necessary information was obtained from clinical charts of patients discharged between the period from January 1, 1975 to December 31, 1985. Complete information was accomplished for 212 pairs of cases and controls. A protective odds ratio (favoring use of AT) = 12.1 (p less than 0.0001, 95% CI 4.2-34.9) was obtained by means of a multiple logistic regression analysis by conditional method. Other variables that entered into the logistic model were: antithrombotic therapy, severity measured by Killip scale and by Norris index. Such findings support the favorable therapeutic role of AT in patients with AMI. PMID- 1866489 TI - [A 51-year-old female with chylous ascites, membranous glomerulonephritis and fever]. PMID- 1866490 TI - [Mycosis fungoides associated with human T-cell lymphotropic virus in Yucatan]. PMID- 1866491 TI - [Splenectomy in thrombocytopenic purpura]. PMID- 1866492 TI - [Effects of malnutrition on infective morbidity in the surgical treatment of portal hypertension (prospective evaluation)]. AB - With the aim of investigating the preoperative frequency of undernutrition and its impact on the infectious morbidity in patients without malignant disease, we studied prospectively 41 patients operated because of portal hypertension between 1987 and 1989 at the Instituto Nacional de la Nutricion. All patients were evaluated through anthropometric analysis and biochemical markers one week before the surgical procedure. A standard scheme of antibiotic profilaxis was used during surgery and the preoperative complications were registered up to discharge from the hospital. Undernutrition was considered when the serum albumin was less than 3 mg/dL or the total lymphocyte count was under 900, associated with a 10% weight loss in six months and reduction of one or more anthropometric parameters below the 30th percentile of the normal value. The group consisted of 17 males and 24 females with a mean age of 48 +/- 14 years old. 35 were Child A, four Child B and two Child C. Ten patients had a distal splenorenal shunt, seven esophageal devascularization and 24 gastric desvascularization with splenectomy. Twenty eight patients were well nourished and 13 undernourished. The two groups were comparable in all parameters except for the nutritional status. In the first group seven patients developed 10 complications and in the undernourished group eight patients had 14 complications (p less than 0.05 chi 2). There was no significant difference in the mortality rate. Infections occurred more frequently in: urinary tract, surgical wound, lung and pleura, and esophageal fistulae was an additional complication. The univariate analysis of the anthropometric parameters did not show significant differences between both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866493 TI - Diagnostic laparotomy in fever of unknown origin. AB - Twenty five consecutive patients with fever of unknown origin (FUO) who underwent diagnostic laparatomy (DL) are reviewed. There were 14 females and 11 males, with a mean age of 34 years. The main symptoms and signs besides fever were malaise, weight loss, varied abdominal complaints, peripheral lymph nodes enlargement, hepatomegaly and splenomegaly. The main laboratory abnormalities were: anemia, leukocytosis, and mild alterations in liver function tests. CT scan was performed in 14 patients: hepatomegaly, splenomegaly and or retroperitoneal nodes were found in 10 of them. During laparotomy, an extensive exploration of intra abdominal organs was performed, taking multiple biopsies for histopathologic and microbiologic analysis. Splenectomy was performed in 17 patients, prophylactic appendectomy in four, and cholecistectomy in one. Laparotomy was useful to establish a diagnosis in 64 percent of cases. The most frequently diagnosed pathologies were lymphoma and tuberculosis. Postoperative morbidity was 12% and mortality was 4%. Mean follow-up was 29 months. When preoperative data were analyzed, no predictive factors were found for a laparotomy with diagnostic success. It is concluded that DL is a useful last-step procedure in the diagnostic work-up for patients with FUO. PMID- 1866494 TI - [Risk factors of the complications of diabetes mellitus]. AB - A total of 1,030 diabetic patients were studied in order to identify factors associated with various complications. A higher proportion of women was found (64.1%). Using regression analysis of prevalence versus the logarithm of the duration of diabetes, a half-life of 5.14 years was calculated. In the study of complications, peripheral neuropathy, amputations, renal impairment, albuminuria, myocardial infarction, cataract and amaurosis were strongly associated with duration of diabetes rather than with the age of the patient or the age at diagnosis; in contrast, blood pressure and impotence correlated better with the age of the patient. A discriminant function analysis permitted to identify several factors as predictors of diverse complication mainly: the duration of the disease, and previous use of insulin (negative correlation). Other predictors were glycemia, alcoholism, smoking habit and intake of legumes (beans). Albuminuria was assessed with a radioimmunoassay procedure and found to be associated with: duration of diabetes, urinary tract infection, systolic blood pressure and amaurosis. Some alimentary habits were also included as predictors of complications. PMID- 1866495 TI - [Capillary hemoglobin as a predictor of the response to the oral intake of iron in children with iron deficiency]. AB - A study was made to determine the prevalence of anemia in apparently healthy children of both sexes aged 6 to 24 months attending the preventive medicine service in a general hospital of the Mexican Social Security Institute in the city of Tapachula, State of Chiapas. One hundred children were studied with a capillary hemoglobin (Hb) determination: 91 had anemia (Hb less than or equal to 11 g/dL). Sixty eight of the anemic children received oral iron for 3 months (3 mg/kg/day): their Hb before and after iron therapy were compared. Considering as responders those with an increment in Hb greater than 1 g/dL, sixty four children (94%) showed a mean increment of 2.6 g/dL. Four were considered as non responders: in 3 the iron supplementation was stopped due to infectious diseases; the fourth case had a Hb increment below 1 g/dL. The use of capillary Hb as a criterium for treating anemic children proved to be a good predictor of response in a population where the prevalence of iron deficiency is high. PMID- 1866496 TI - [Levels of carboxyhemoglobin in smokers and non-smokers from 2 cities of the Mexican high plateaux]. AB - Carboxyhemoglobin levels (COHb) were determined in residents of two Mexican cities (Mexico City and Toluca) at altitudes of 2200 and 2600 meters above sea level. The figures in non-smokers of both cities were slightly higher than those seen at sea level by others: 1.63% in Mexico City and 1.54% in Toluca versus 0.5 1% at sea level. There were no intercity differences in smokers and non-smokers, but there were intergroup differences in both cities (p less than 0.01 in Mexico City, and p less than 0.05 in Toluca). Our findings suggest that the most important source of carbon monoxide in smokers is tobacco smoking, and that the COHb level may be reliable index to establish active smoking. PMID- 1866498 TI - Abscence of changes in the protein profile of erythrocyte membranes in Duchenne patients. AB - Numerous authors have suggested an impairement in protein synthesis as a possible cause for the failure in growth with degeneration of the skeletal muscles protein content present in Duchenne muscular dystrophy (DMD). Others have supported the use of in vitro erythrocyte membranes as a model of the sarcolemmal changes in DMD. Very recently, in vitro decrease in protein synthesis of ribosomal proteins of skeletal muscle cells, fibroblasts and erythrocytes of DMD patients have been reported. We studied the protein profile of erythrocytic membranes of 5 patients with confirmed DMD by means of SDS-polyacrylamide discontinuous gels electrophoresis (method with which we detected changes in the electrophoretic profile of erythrocyte membrane proteins induced by myotonizing drugs) and compared it with the profile of 5 healthy subjects of a similar age range. No differences between the two groups were apparent, rising doubts about the appropriatness of the erythrocyte membrane as an in vivo model of molecular changes in DMD and about the limitations of unidimensional electrophoresis as a suitable method for the detection of such changes. PMID- 1866497 TI - [Prevalence of human immunodeficiency virus (HIV) infection and its relationship with other sexually transmitted diseases in a group of prostitutes from Huixtla, Chiapas]. AB - We investigated the HIV prevalence rate in 106 female prostitutes residing in Huixtla, State of Chiapas, which is a small town in the southeastern part of Mexico, from February of 1989 to January of 1990. We used an immunoenzymatic method (Serodia). The mean age was 35 years ranging from 17 to 43. Sixty six women (62%) were from Central America, and the remainder had been born in Mexico. The HIV antibody was not detected in the women, but 39 (37%) had a sexually transmitted disease: the more frequent were condolomatosis, candidiasis, trichomoniasis, gonorrhea, and syphilis. PMID- 1866499 TI - [Radiographic measurement of the total pulmonary capacity: comparison of 2 planimetric methods]. AB - We analyzed accuracy and reproducibility of a radiographic method for calculation of total lung capacity (TLC) from the sum of pulmonary area. Pulmonary area from a routine postero-anterior and lateral chest radiography was measured by two methods: using a planimeter (standard) and with a virgin radiographic plaque with lines separating squares of 1cm per side. Plethismographic TLC was obtained adding the functional residual capacity to inspiratory capacity. We studied 13 healthy subjects (mean age of 30 years, eight males), 13 with interstitial lung disease (mean age of 45 years, two males) and 12 with chronic bronchitis or emphysema (mean age of 63 years, three males). Measured TLC varied from 1.9 to 7.2 liters. The linear regression equation found was: TLC = 0.007 total lung area (cm2) 0.572, R = 0.906, P less than 0.001 which is very similar to that reported by Harris et al.8 Interobserver variability in the measurement was very small taking into account that no efforts were made to uniformize the observers. Main interobserver differences were in the tracing of the lung limits, and not in the actual measurement of the lung area. We found no differences between the two methods for measuring lung area except that the planimeter is faster and more reproducible. Radiographic method for measuring TLC is accurate and available in most places. PMID- 1866500 TI - [Primary non-Hodgkin's lymphoma of the lung]. AB - A case of small and large cells non Hodgkin lymphoma with an unusual involvement of the lung is presented. The tumor was located in the inferior lower lobe of the right lung and coincided with hemorrhagic pleural effusion. The cytopathological study of the fluid was negative for neoplastic cells, so were the aspiration biopsy of the lung and the pleural biopsy. The transmission and scanning electron microscopic study of the pleural fluid demonstrated lymphoid atypical cells. The patient was treated by resection of the lower right lobe and pleurectomy. The difficulties in the differential diagnosis of this type on non Hodgkin lymphoma are discussed. The importance of scanning and transmission electron microscopy is stressed when the light cytologic studies are negative in processes suggestive of being neoplasms. After one year of the lobectomy and treatment with vincristine epirubicin-cyclophosphamide and methyl-prednisolone, the patient is in good condition without evidence of neoplastic activity. PMID- 1866501 TI - [Reticulocytopenia and neutropenia in 3 patients with idiopathic autoimmune hemolytic anemia]. AB - Retyculocytopenia and neutropenia or both abnormalities are very infrequent findings during the evolution of patients with acquired autoimmune hemolytic anemia (AIHA). In this paper we describe the clinical cases of three patients with AIHA in whom six different periods of reticulocytopenia were identified; the first two patients also had neutropenia. At the moment of the diagnosis of the cytopenias, the patients did not have a systemic disease, a viral infection or received immunosuppression able to produce them. In every patient the bone marrow cellularity was increased mostly at the expense of normal and macroerythroblasts, containing significant amounts of the other hematopoietic cells. After the diagnosis of AIHA, the patients received supplementary treatment with folic acid which did not produce a remission. The remissions were related to steroids: the neutrophil counts increased importantly one to ten days after starting the steroid administration, whereas reticulocytes reappeared more slowly from 7 to 30 days post-initiation. In patients with AIHA the occurrence of reticulocytopenia and neutropenia have been related to several causes. The favorable responses to steroids in our cases suggests a relationship of steroid with the immunological changes in AHA. It should be pointed out that it is necessary to prolong the followup as done in our three cases. Although these cytopenias may be independent from the hemolytic anemia, we feel our cases suggest that they could be manifestations of a pathologic state not yet characterized. PMID- 1866502 TI - [Severe pseudoachondroplasia. Presentation of a case]. AB - A male child who has the clinic and radiologic characteristics of type IV pseudoachondroplasia an autosomal recessive inherited disease, is described. For genetic counselling purposes, the clinic features and differential diagnosis and its classification are discussed. PMID- 1866503 TI - [Idiopathic portal hypertension]. AB - Patients with portal hypertension without a demonstrable cause have been reported in the literature under several different terms, such as tropical splenomegaly, phlebosclerosis, obliterative portal venopathy of the liver, hepatoportal sclerosis, noncirrhotic portal fibrosis and idiopathic portal hypertension (IPH). Such patients have been described worldwide, with a greater frequency in India and Japan. The etiology of IPH is still unknown, although some of the theories that have been proposed are: exposure to toxic substances or drugs, relationship with the hepatitis-B virus, immunologic abnormalities, systemic or intra abdominal infections and clotting abnormalities. The main histopathologic findings are periportal fibrosis, obliteration of small portal veins and sclerosis of the interhepatic portal system. Although these abnormalities could be secondary to portal hypertension, it has been proposed that the vascular changes are the primary event that leads to portal hypertension. The site of increased resistance in IPH is found at the presinusoidal level with some component at the sinusoidal and postsinusoidal level. The main symptoms and signs in IPH are upper gastrointestinal tract bleeding secondary to esophago-gastric varices, symptoms related to anemia, and splenomegaly. The long-term prognosis for patients with IPH is better than for cirrhotic patients, with a 77% survival at ten years. Variceal bleeding is the main cause of death, and some treatment to prevent bleeding or its recurrence is warranted. Although no comparative trial has been performed in IPH patients, the surgical management could be the first choice for elective treatment in these patient without liver failure, because of the high re-bleeding rates with chronic sclerotherapy. Pharmacologic management could be considered for prophylactic treatment of these patients. PMID- 1866504 TI - [The challenge of evaluating clinical competence]. AB - The study is divided in two parts. The first one deals with theoretical aspects of evaluation. In the second part, the development of an instrument intended to explore clinical competence is presented. The importance of considering evaluation as part of a research process is emphasized in the first part. The diverse theoretical and action trends in the field of education are synthetized in two main tendencies: the active-participating and the passive-receptive. The influence of these two tendencies in the selection the objects for evaluation is also discussed. An evaluation instrument developed by us to explore clinical competence is placed within the active-participating tendency of education; the present state of this instrument is given in the second part. The instrument consists of multiple choice options of the true, false, don't know type. The instrument in its present version is the result of a long validation process. It explores particularly iatrogenic behaviors by omission or commission. The sample studied were 457 applicants for specialization courses in medicine. Of these, 127 were foreign applicants. The instrument was applied to the whole sample in one single session. The results showed a low general clinical competence, with similar results in mexican and foreign applicants. A clear difference was found in commission iatrogenia which was significantly more frequent than omission iatrogenia. The theoretical superiority of our test in relation the others is discussed. PMID- 1866505 TI - [Ethical conflicts associated with investigation in patients with HIV infection with or without AIDS]. PMID- 1866506 TI - [Ethics and research in neurosurgery]. AB - Ethical issues related to neural grafting are numerous. Experimental research on animals give much hope to get in next future a treatment in favour of numerous neurological disorders which are incurable at present. We must follow ethical recommendations of the NIH human fetal tissue transplantation research panel. According to the rapidity of knowledge growing in this field, so as in others, it would not be adequate to favour any law project on this subject, which does not mean that we could have something to hide. On the contrary, we would like to favour the diffusion of the works made by all ethical committees in our country. This could be one of the aims of the future National Bioethical Committee. PMID- 1866507 TI - [Chronic asymptomatic hypereosinophilia. Apropos of a case of occupational toxocariasis]. AB - The authors observed a case of asymptomatic toxocariasis in a lady aged 60, engaged in dog-breeding since twenty years. The various causes of hypereosinophilia are discussed. The epidemiology of Toxocariasis and the essential role of serologic tests--in particular ELISA detection of a larval antigen--are recalled. In this particular case, therapeutic abstention is justified. PMID- 1866508 TI - [Pain and cancer]. AB - Pain is one of the most frequent symptoms encountered in oncology which, regarding its complexity and its effects on quality of life, will be better treated with a multidisciplinary approach, for in and out-patients. The knowledge of the pain syndromes associated with an accurate use of pain medicine provide a rapid control of the symptomatology. A coherent use of opioids, the introduction of new drug delivery systems, and the use of new molecules offer new horizons in the control of cancer pain. PMID- 1866509 TI - [Medical studies at the Free University of Brussels at the approach of the year 2000]. PMID- 1866510 TI - [What is your diagnosis? Attendant myocarditis in viral infection]. PMID- 1866511 TI - [Long-term trans-tracheal oxygen therapy. Simple management for the patient- improved compliance]. AB - Long-term oxygen therapy is an established treatment of severe hypoxemia in patients with chronic obstructive or other pulmonary diseases. Quality of life and survival time can be improved significantly. Objective patient evaluation and compliance are most important. The transtracheal oxygen therapy is an alternative method to nasal cannulas for oxygen supply. Cosmetic problems and nasal discomfort are avoided. The oxygen flow-rate can be reduced by up to 50%. If an on demand-system is used, the oxygen flow-rate can be adapted to exercise. The change and cleaning of the catheter is easy and is performed twice daily by the patient himself. PMID- 1866512 TI - [The clinical diagnosis of lung embolism]. AB - The clinical classification, pathophysiology and often difficult diagnosis of acute pulmonary embolism are reviewed. The diagnostic power of subjective and objective clinical symptoms and the diagnostic procedures (electrocardiogram, chest X-ray, echocardiography, pulmonary arteriography, pulmonary scintigraphy, determination of arterial blood gases) are evaluated and an actual investigative plan outlined. Diagnostic problems and frequent pitfalls are discussed. The often non characteristic and masked course in acute and chronically recurrent pulmonary embolism is emphasized. PMID- 1866513 TI - [The drug therapy of chronic cor pulmonale]. AB - Chronic cor pulmonale is defined as right heart hypertrophy or right ventricular dilatation and/or chronic right heart failure. There are many etiologies which largely determine mortality and drug therapy, but the common cause is increased right ventricular work from primary or secondary pulmonary hypertension assuming two prototypes, the asphyxial and the vascular obliterative type. The main focus of this review concentrates on the various drugs to reduce pulmonary vascular pressure and resistance. The value to correct hypoxaemia is mentioned with regard to its demonstrated important effect of asthmatic patients with cor pulmonale. Continuous oxygen therapy and a potential therapy by almitrine, a respiratory stimulant, have been suggested. Phosphodiesterase inhibitors and dopaminergic drugs have been used successfully to improve right cardiac function in a small number of patients. The use of prostacyclin has a large potential to effectively correct pulmonary vascular haemodynamics but its use is fairly limited by the need of continuous intravenous application. New oral drugs under investigation which stimulate endogenous prostacyclin as well as thromboxane synthetase inhibitors still need further evaluation but might be of potential benefit. The comparison of the side-effects due to vasodilators and calcium antagonists argues for the use of calcium channel blockade for patients with pulmonary hypertension. To define the role of angiotensin converting enzyme inhibitors or the more recently introduced potassium channel openers for treatment of chronic cor pulmonale still await detailed, controlled studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866514 TI - [The therapy of chronic respiratory insufficiency]. AB - The treatment of chronic respiratory failure aims to influence the underlying disease and to alleviate the pathophysiologic consequences. Respiratory stimulants, long-term oxygen-therapy as well as mechanical stabilization of the upper airways and ventilation at home are discussed. PMID- 1866515 TI - [The significance of proteinuria]. PMID- 1866516 TI - [What should be done in case of elevated serum creatinine?]. PMID- 1866517 TI - [Glomerulonephritis with mesangial IgA deposits--Berger's disease]. PMID- 1866518 TI - [Approach to isolated hematuria]. PMID- 1866519 TI - [What should be done with a patient with calculi?]. PMID- 1866520 TI - [Intradermal tuberculin reaction]. PMID- 1866521 TI - [Oxalosis (type 1 primary hyperoxaluria)]. PMID- 1866522 TI - [The child and the campaign against cancer]. PMID- 1866523 TI - [A psychiatrist among the surgeons]. PMID- 1866524 TI - [Epidemiological approach to anxiety disorders in children]. PMID- 1866525 TI - Sleep deprivation in the rat: XII. Effect on ambient temperature choice. AB - Previous studies of total sleep deprivation in the rat by the disk-over-water method had shown an initial rise in body temperature (Tb), a later decline to below baseline levels, and a progressive rise in energy expenditure (EE). To evaluate the role of changes in temperature setpoint in these results, the ambient temperature choices (Tc) of six totally sleep-deprived (TSD) rats and their yoked control (TSC) rats were determined by the position in a thermally graded alley at which they chose to fall asleep. (Rats were removed from the alley and returned to the deprivation apparatus 1 min after sleep onset). Sleep deprivation was continued until TSD rats were near death. Tb and EE results were like those of the earlier studies. Tc rose progressively from 26.8 degrees C during baseline to 49.9 degrees C near the end of the deprivation period in TSD rats, whereas TSC rats showed only modest, nonsignificant increases. The attempt by TSD rats to get warmer, in spite of an elevated Tb, indicates a raised setpoint for behavioral thermoregulation and suggests that the increase in EE was also, at least in part, an attempt to reach an elevated setpoint. The progressively raised Tc also indicates that the late decline in Tb was a decline below setpoint rather than a response to a lower setpoint. Because EE increased, Tb decline must have resulted from excessive heat loss. Thus, TSD in the rat produced two thermoregulatory deficits-increased setpoint and excessive heat loss.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866526 TI - Pupillometric assessment of excessive daytime sleepiness in narcolepsy-cataplexy. AB - Ten untreated patients with narcolepsy-cataplexy and age- and sex-matched normals between the ages of 20 and 71 years underwent pupillometric analyses immediately prior to each of five multiple sleep latency test sessions. Although narcoleptics were sleepier as indicated both by their Stanford Sleepiness Scale ratings and by their latencies to sleep onset, the baseline pupil diameter, pupillary light reflex, and pupillary orienting response did not differentiate between groups. Narcoleptics did, however, exhibit a significantly greater frequency of spontaneous oscillations in the dark-adapted state than did controls. These findings indicate that pupillary stability may serve as a supplementary diagnostic tool for narcolepsy-cataplexy. The results are discussed with the view that psychosensory restoration of alertness, among other extraneous variables, must be controlled when utilizing pupillometric techniques. A review of the literature indicates a variety of methodological and statistical shortcomings that must be amended. Suggestions are made for improving the reliability and validity of the pupillometric approach. PMID- 1866527 TI - Sleepiness/alertness on a simulated night shift following sleep at home with triazolam. AB - Physiological sleep tendency during a simulated night shift schedule was examined in 15 middle-aged subjects following daytime sleep after administration of triazolam or placebo. A double-blind, counterbalanced, crossover design involving two tours of five laboratory nights and four daytime home sleep periods was used. Triazolam lengthened daytime sleep as measured by wrist actigraph and improved nighttime alertness as measured by the MSLT. Sleepiness was most profound during the early morning hours (0430 to 0630) but improved significantly across nights for both conditions. Repeated test of sustained wakefulness latencies and simulated assembly line task performance decreased slightly across the night, but there were no significant condition effects. Subjective data tended to support objective measures, although Stanford Sleepiness Scale ratings indicated that subjects did not perceive improved alertness at night after triazolam-aided daytime sleep. PMID- 1866528 TI - The dynamics of the first sleep cycle. AB - Eight subjects participated in an experiment in which sleep stages and electroencephalographic (EEG) power density during the first sleep cycles (and where such appeared, also second cycles) were studied in a design involving 8, 4, 2 or 0 hr of progressively postponed night-time sleep. Each of these four manipulations was followed by a day-time sleep beginning at 1100 hr. No significant changes in the duration of the first sleep cycle appeared. As the prior sleep loss increased both SWE (slow-wave energy; accumulated EEG delta power density) and SWA (slow-wave activity; EEG delta power per minute) increased during the 1100-hr sleeps. This was observed for the entire cycles, the nonrapid eye movement (NREM) periods, and the SWS periods, respectively. SWS latency decreased and SWS duration increased, respectively, markedly with prior waking. Also, for the progressively postponed sleeps (started at 2300 hr, 0300 hr, 0500 hr and 1100 hr) there were changes, but not as clear. After 28 hr of continuous waking there was a marked increase of SWA during SWS. Also, at this level there was a spill over of SWA to the second cycle. It is suggested that there might be a limit to the amount and intensity of SWS that can be accommodated in the first sleep cycle and that this limit is reached before the appearance of REM sleep. PMID- 1866529 TI - The effect of sleep deprivation on cerebral glucose metabolic rate in normal humans assessed with positron emission tomography. AB - This study is the first report on the effects of total sleep deprivation (about 32 h) on regional cerebral glucose metabolism during wakefulness in man, using positron emission tomography (PET) with F-18 deoxyglucose (FDG). Sleep deprivation leads to a significant reorganization of regional cerebral metabolic activity, with relative decreases in the temporal lobes and increases in visual cortex. Absolute glucose metabolic measurements indicate a decrease in thalamus, basal ganglia, white matter, and cerebellum. No overall decrease in whole brain metabolism was noted after sleep deprivation. As expected, sleep deprivation significantly reduced visual vigilance as assessed by the continuous performance test and this decrease was correlated significantly with reduced metabolic rate in thalamic, basal ganglia, and limbic regions. PMID- 1866530 TI - Periodic movements of the legs during sleep associated with rises in systemic blood pressure. AB - We report the relationship between periodic leg movements during sleep and recurrent rises in systemic blood pressure in a patient with narcolepsy. The mean increase in systolic blood pressure following leg movements was 23%, which is of the same order as the rises seen in patients with obstructive sleep apnea. Following treatment with temazepam, the swings in blood pressure were unchanged despite considerably less electroencephalographic evidence of cortical arousal. PMID- 1866531 TI - Hygroscopic condenser humidifier as a solution to nasal dryness due to nasal CPAP treatment for obstructive sleep apnea syndrome. AB - We report an apparent solution to nasal dryness for patients with obstructive sleep apnea syndrome treated with nasal continuous positive airway pressure (CPAP) when a hygroscopic condenser humidifier is introduced into the CPAP circuit. Six patients underwent a 5-h test period of nasal CPAP therapy with a mask containing a hygroscopic humidifier. The water vapor showed a statistically significant increase in both inspired and expired gases. The relative humidity of the inspired gases increased significantly. The levels of O2 and CO2 in the respired gases did not change. When patients were asked about nasal dryness at the end of the test, all of them reported marked improvement. PMID- 1866532 TI - National Institutes of Health Consensus Development Conference Statement: the treatment of sleep disorders of older people March 26-28, 1990. PMID- 1866534 TI - Bibliography of recent literature in sleep research. PMID- 1866533 TI - Trends in the sleep literature: 1968-1988. PMID- 1866535 TI - Changing pattern of bone and joint infections due to Staphylococcus aureus: study of cases of bacteremia in Denmark, 1959-1988. AB - Of the 15,170 cases of bacteremia due to Staphylococcus aureus that occurred in Denmark between 1959 and 1988, we review 525 cases of acute hematogenous osteomyelitis and 185 cases of septic arthritis that developed subsequent to the bacteremia and 134 cases of contiguous osteomyelitis in which the bacteremia developed secondarily. The pattern of acute infections of bones and joints has changed over the three decades studied. The frequency of secondary bone or joint infections due to S. aureus bacteremia has changed, as have the phage-type pattern and antibiotic resistance of the infective strains. The prevalence of hospital-acquired cases has increased and the age distribution of patients has changed, as is reflected in an increasing number of older patients. The localization of hematogenous osteomyelitis has shifted, and the vertebral column is now the most common site of infection. The rate of chronic cases of osteomyelitis that occur following acute hematogenous osteomyelitis has been reduced from 34% to 6%. The mortality associated with S. aureus bacteremic infections of bones or joints is low compared to that associated with other cases of S. aureus bacteremia. PMID- 1866536 TI - Serologic diagnosis of human brucellosis: analysis of 214 cases by agglutination tests and review of the literature. AB - The serum agglutination test (SAT) and 2-mercaptoethanol (2ME) agglutination were used in studies of the sera of 214 patients in whom brucellosis was suspected. On the basis of historical, epidemiologic, clinical, and serologic data, four groups were identified: group I (108 cases) had negative agglutination reactions, and brucellosis was considered unlikely; group II (57 cases) had positive agglutination reactions, and active brucellosis was diagnosed; group III (37 cases) had positive agglutination reactions, but other factors--notably, a history of prior infection--made inactive brucellosis likely; and group IV (12 cases) had positive agglutination reactions, but insufficient data were available for further classification. Most patients with active brucellosis had agglutinin titers of greater than or equal to 160; however, no single titer was always diagnostic. Although more sensitive tests are available, agglutination reactions provide data sufficient to differentiate active from inactive disease when other factors are considered and follow-up sera are tested. This article discusses individual cases and reviews the literature on the diagnosis of brucellosis. PMID- 1866537 TI - Splenic abscesses due to Mycobacterium tuberculosis in patients with AIDS. AB - Among 60 patients with AIDS seen at our institution, two had splenic abscesses due to Mycobacterium tuberculosis without pulmonary tuberculosis. In both cases splenic abscess was the first manifestation of AIDS; the patients had prolonged fever and had lost weight and experienced malaise; slight hepatomegaly was noted in both instances and peripheral lymphadenopathy in one. Chest radiography gave normal results in one case and showed hilar lymphadenopathy in the other. Ultrasonographic findings were characteristic: homogeneous hepatomegaly and splenomegaly, with multiple filling defects of variable size. Diagnosis required splenectomy in one case and biopsy of cervical lymph nodes in the other. In both cases Ziehl-Neelsen staining gave positive results; M. tuberculosis grew from a culture of splenic tissue of one patient and from a culture of lymph nodal tissue of the other. There was a rapid response to antituberculous therapy. Splenic tuberculosis seems to be a distinct extrapulmonary entity in patients with AIDS. Ultrasonographic images are useful for diagnosis and follow-up. PMID- 1866538 TI - Peritonitis due to Prototheca wickerhamii in a patient undergoing chronic ambulatory peritoneal dialysis. AB - A 72-year-old man who was undergoing chronic ambulatory peritoneal dialysis developed peritonitis due to Prototheca wickerhamii. Results of in vitro sensitivity testing revealed that the organism was sensitive to amphotericin B (MIC, 0.4 micrograms/mL) but resistant to fluconazole (MIC, greater than 80 micrograms/mL). The patient was successfully treated medically with a combination of intravenous amphotericin B and oral doxycycline. PMID- 1866539 TI - Human infection caused by Exophiala pisciphila: case report and review. AB - One year after receiving a liver transplant and 2 months after treatment with high doses of steroids and monoclonal anti-CD3 for an episode of rejection, a 38 year-old woman developed a skin papule above the left medial malleolus. The papule, which at first had an annular shape, evolved into a pustule, ulcerated, drained, and assumed a crusted verrucous appearance. Multiple satellite papules appeared around the lesion, which was incompletely excised and thought to represent squamous cell carcinoma. Review of the histologic slides revealed pseudoepitheliomatous hyperplasia with multiple epidermal and dermal abscesses, pigmented hyphae, and yeast-like forms. Culture of material obtained at reexcision yielded a dematiaceous fungus that was identified as Exophiala pisciphila. No evidence of dissemination was found. This represents a unique report of human infection with this fungus, a well-recognized pathogen of fish. Except for the absence of sclerotic bodies, the clinicopathologic features resembled those of chromoblastomycosis rather than those of the subcutaneous cystic form of phaeohyphomycosis often associated with species of Exophiala. PMID- 1866540 TI - Endocarditis due to Trichosporon beigelii: in vitro susceptibility of isolates and review. AB - Infection with Trichosporon beigelii is an uncommon cause of endocarditis. Of the eight cases of T. beigelii endocarditis that have been reported (one herein and seven previously), six involved prosthetic heart valves and two involved native heart valves. The clinical manifestations of this infection included embolization of the superficial femoral artery or of the bifurcation of the posterior tibial and peroneal arteries in three of these patients (two with prosthetic valve and one with native valve endocarditis). In seven of the eight reported cases, blood cultures were positive for the organism. Although clinical isolates of the organism are generally reported to be susceptible to amphotericin B, isolates can vary in their sensitivities to antifungal agents in vitro depending on the methodology used, and clinical response to therapy with antifungal agents in a regimen that includes amphotericin B is generally poor. Only two of six patients who were treated with antifungal agents survived endocarditis caused by T. beigelii and were apparently cured; one of these patients was also managed surgically with valve replacement. Infection with T. beigelii should be considered in the differential diagnosis of endocarditis in immunocompetent patients, particularly those who have a prosthetic heart valve. Rapid, aggressive therapy may be necessary to eradicate this organism. PMID- 1866541 TI - Bacterial infection as a complication of liver transplantation: epidemiology and risk factors. AB - A retrospective survey was undertaken to characterize the epidemiology of bacterial infection in 79 patients who underwent 103 operations for orthotopic liver transplantation. Fifty-four patients (68%) developed 115 bacterial infections (1.46 episodes per patient), and seven patients died as a result of these infections. Fifty-three percent of bacterial infections occurred within 2 weeks after transplantation and were designated as early infections. The most common sites of infection were the abdomen (35 cases), the bloodstream (31 cases), and the surgical wound (19 cases). Aerobic enteric gram-negative bacilli were the predominant pathogens, and other pathogenic organisms were enterococci, staphylococci, and Pseudomonas bacteria. Logistic regression analysis identified prolonged duration of surgery (greater than or equal to 8 hours) and an elevated bilirubin level (greater than or equal to 12 mg/dL) as risk factors for early bacterial infection at any site; risk factors for abdominal or wound infection were prolonged duration of surgery, increased operative transfusion requirement (greater than or equal to 2 blood volumes), and prior hepatobiliary surgery. Awareness of the sites, pathogens, and time of onset of bacterial infection provides a basis for improved prophylaxis and empiric therapy. PMID- 1866542 TI - Ceftazidime plus amikacin versus ceftazidime plus vancomycin as empiric therapy in febrile neutropenic children with cancer. AB - Two antibiotic regimens, ceftazidime plus amikacin and ceftazidime plus vancomycin, were compared in a prospective, randomized clinical trial as empiric therapy in febrile granulocytopenic children with cancer. The rate of response was similar in the two groups (66% vs. 77%). The prevalence of secondary gram negative bacteremia was higher--but not significantly higher--in the group receiving vancomycin. Adverse reactions also occurred more often in the latter group (35% vs. 4%). Mortality did not differ significantly in the two groups. Adjustment for independent predictors of response to treatment by means of multivariate analysis confirmed the lack of any remarkable difference between the responses to the two regimens. We conclude that the use of vancomycin instead of amikacin in combination with ceftazidime does not significantly improve the outcome of treatment of fever and infection in granulocytopenic children with cancer and that the use of vancomycin is associated with an increased frequency of both secondary infections due to gram-negative bacteria and adverse reactions. PMID- 1866543 TI - Antibiotic misuse in two clinical situations: positive blood culture and administration of aminoglycosides. AB - Antibiotic use was examined among randomly and prospectively selected cohorts of 79 patients with a positive blood culture and 88 patients given aminoglycosides for a variety of reasons. Appropriateness of antibiotic use was judged daily for each agent according to specific criteria of misuse. For patients with a positive blood culture, 14.3% of antibiotic-days were judged inappropriate in some regard, while for patients given aminoglycosides, 10.2% of antibiotic-days were thought to be inappropriate. The patterns of misuse were similar for the two groups despite disparate selection criteria. The unnecessary use of antibiotics was the single most common type of misuse in both groups, but errors in dosing collectively accounted for nearly one-half of antibiotic misuse. These results suggest that a variety of factors are responsible for misuse of antibiotics. Although the data presented do not allow conclusions about the optimal methods for control of antibiotic misuse, they imply that a multifaceted approach is probably required. PMID- 1866544 TI - Listeria monocytogenes infections in patients with AIDS: report of five cases and review. AB - Five patients with AIDS and Listeria monocytogenes infection (three cases of bacteremia and two of meningitis) are reviewed. Four patients had prior or concurrent gastrointestinal illness. Two patients received corticosteroids. A 7- to 21-day course of ampicillin was administered with or without a 7- to 14-day course of gentamicin. This regimen was effective, with no evidence of relapse 7-8 months after therapy was discontinued. The relative infrequency of infection with L. monocytogenes in AIDS patients is unexpected. Tumor necrosis factor (TNF) appears to be essential in the inhibition of Listeria in vivo. Elevated levels of TNF in AIDS patients may be protective against listeriosis and thus help explain the low prevalence of listerial infection in this population. Nonetheless, although L. monocytogenes is an uncommon cause of illness in patients infected with the human immunodeficiency virus, it cannot be dismissed as a cause of undefined meningitis or sepsis. PMID- 1866545 TI - Abdominal abscess due to Cardiobacterium hominis and Clostridium bifermentans. AB - A case of abdominal abscess and bacteremia due to Cardiobacterium hominis and Clostridium bifermentans was successfully treated with surgical drainage and ampicillin-penicillin. This case represents the rare occurrence of C. hominis infection without apparent endocarditis. PMID- 1866546 TI - Choleriform syndrome and production of labile enterotoxin (CT/LT1)-like antigen by species of Salmonella infantis and Salmonella haardt isolated from the same patient. AB - Isolates of Salmonella infantis from the stool and blood and an isolate of Salmonella haardt from the stool of a patient with choleriform diarrhea produced labile enterotoxin (CT/LT1)-like antigen. Genetic and molecular experiments indicated that the production of CT/LT1-like antigen was chromosomally encoded. PMID- 1866547 TI - Fatal varicella in an adult: case report and review of the gastrointestinal complications of chickenpox. AB - An unusual and fatal case of primary varicella in an adult is presented. Involvement of the small intestine first manifested as abdominal pain and later progressed to gastrointestinal bleeding with subsequent dissemination of the infection. Although it has previously been speculated that gastrointestinal bleeding can result from infection with the varicella-zoster virus, the data from this case include histologic and cultural evidence that supports the clinical observations. The literature has been reviewed, and the management of this patient has been critically evaluated. PMID- 1866548 TI - Survival and disinfectant inactivation of the human immunodeficiency virus: a critical review. AB - The possibility of contracting acquired immunodeficiency syndrome (AIDS) through accidental or inapparent parenteral exposure to human immunodeficiency virus (HIV) has raised concerns among recipients of blood products, health-care professionals, and others who have contact either with HIV or with AIDS patients. Along with these concerns has come an increasing interest in the physical and chemical methods that may be used to inactivate HIV in blood products and other contaminated fluids as well as on contaminated objects and surfaces. This review critically examines the available information on the survival of HIV and the methods used for its inactivation, particularly those that rely on chemical disinfection. Although the risk of acquiring HIV from contaminated materials may be slight compared with that of acquiring other blood-borne pathogens, such as hepatitis B virus, the effectiveness of disinfectants used under clinical conditions may have been overestimated. PMID- 1866549 TI - Survival and vehicular spread of human rotaviruses: possible relation to seasonality of outbreaks. AB - In developing countries rotavirus infections account for nearly 6% of all diarrheal episodes and for 20% of diarrhea-associated deaths of young children. Even in industrialized countries rotavirus diarrhea in the young is among the leading causes of hospitalization. In temperate regions institutional outbreaks of the disease occur mainly in cold dry weather, whereas in tropical settings the seasonality is less well defined. Waterborne outbreaks of rotavirus gastroenteritis have been recorded; air, hands, fomities, and food may also act as vehicles for this infection. Rotaviruses can survive for weeks in potable and recreational waters and for at least 4 hours on human hands. In air and on nonporous inanimate surfaces, the survival of rotaviruses is favored by a relative humidity of less than or equal to 50% and viral infectivity can be retained for several days. Rotaviruses are relatively resistant to commonly used hard-surface disinfectants and hygienic hand-wash agents. PMID- 1866551 TI - Management of the immunocompromised patient: impact of fungal infections. Introduction. PMID- 1866550 TI - Impact of temperature elevation on immunologic defenses. AB - Fever is a common response to infection and to other challenges to host defense. Temperature elevation has been associated with effects on the recognition, recruitment, and effector phases of the immune response. Specific immunologic responses are generally enhanced in the setting of temperature elevation within the physiologic range but not the supraphysiologic range. In contrast, natural immune responses may be unchanged or adversely affected. Temperature elevation appears to affect primarily the phase of recognition and sensitization or activation of mononuclear leukocytes. T lymphocyte responses (and/or the interactions of T lymphocytes with monocytes-macrophages) are enhanced for generation of effector cells. The activities of the effector cells, once generated, are usually not enhanced--or may even be depressed--by temperature elevation, but decreases are more than offset by increased T helper function. Overall, the data suggest that temperature elevations of the febrile response constitute a beneficial component of effective host defense. PMID- 1866552 TI - The use of amphotericin B in nosocomial fungal infection. AB - The use of potent broad-spectrum antibacterial agents, the increasing number of immunocompromised hosts, and the use of invasive treatment modalities have exacerbated the problems involved in the management of nosocomial fungal infection. The hospital records at a tertiary-care medical center were retrospectively reviewed in an effort to determine the magnitude of these problems. A plethora of fungal species were isolated from patients. Hospital infection surveillance revealed between 30 and 40 nosocomial yeast infections per month, with 20% of nosocomial urinary tract infections caused by yeasts rather than by bacterial pathogens and one or two cases of fungemia per week. Although these figures represent a large number of nosocomial fungal infections, a significant increase in the number of such infections over the last several years could not be documented. The use of amphotericin B was found to have increased each year. The patterns of use of amphotericin B changed little between 1983 and 1987, but the number of patients treated with this agent increased dramatically. PMID- 1866553 TI - The growing problem of mycoses in patients infected with the human immunodeficiency virus. AB - With the rapid increase in cases of AIDS over the past 10 years, certain mycoses have dramatically risen in frequency, particularly those contained by T cell mediated mechanisms of host defense. In this clinical setting mucocutaneous candidiasis as well as systemic cryptococcosis, histoplasmosis, and coccidioidomycosis pose special diagnostic and/or therapeutic challenges. Compared with fungal infections in general, AIDS-associated mycoses are more likely to have nonspecific clinical manifestations; moreover, treatments effective in other settings seldom are curative. These problems have led to new vigilance regarding mycoses in the differential diagnosis of complications of infection due to the human immunodeficiency virus (HIV) and have necessitated a redefinition of goals: the aim is now to suppress rather than cure infection in most cases. This change has stimulated trials of new antifungal agents and regimens particularly designed to facilitate long-term outpatient management of mycoses without interfering with treatment of either HIV infection itself or other concomitant complications. PMID- 1866554 TI - Candida and Aspergillus infections in immunocompromised patients: an overview. AB - Infection is a major cause of morbidity and mortality in granulocytopenic patients. With the increasing use of aggressive chemotherapy causing prolonged granulocytopenia in patients with cancer, the risk of disseminated fungal infection has increased. Although Candida and Aspergillus species are known to be the most common fungal pathogens responsible for disseminated infection, diagnosis of such infection may be difficult. The use of empiric amphotericin B for presumed disseminated candida infection may reduce morbidity caused by this fungal pathogen; moreover, amphotericin B remains the agent of choice for established candida infection, although fluconazole shows promise. The addition of flucytosine may enhance the efficacy of amphotericin B against Candida. Aspergillus infection is more difficult to treat. Early recognition of invasive aspergillosis and use of high-dose amphotericin B (1.0-1.5 mg/[kg.d]) alone or in combination with flucytosine may reduce associated mortality. More active, less toxic antifungal agents are needed to improve the efficacy of treatment and prophylaxis of disseminated fungal infection. PMID- 1866555 TI - Problems in the diagnosis of invasive fungal diseases. AB - Invasive mycoses are escalating in frequency in contemporary medicine; most dramatic is the rise in the prevalence of opportunistic fungal infections among immunocompromised hosts. Despite increased awareness among physicians and greater mycologic acumen, morbidity and mortality remain substantial. In part, this situation is due to the difficulties encountered in the diagnosis of fungal infections by both the clinician and the laboratorian. Some of the factors contributing to these difficulties include the abrogation of the immune response associated with improved medical technology, the impact of AIDS, the invasion of the immunocompromised host by fungi previously considered to be saprobic, and the minimal mycologic training of medical personnel. Research efforts are under way that may be expected to improve the diagnosis and treatment of invasive mycotic diseases in the near future. For the present, it is recommended that mycologic training be encouraged and improved for all health care professionals. PMID- 1866556 TI - Empiric therapy with amphotericin B in febrile granulocytopenic patients. AB - The early diagnosis of invasive fungal infection in granulocytopenic patients remains unreliable. Granulocytopenic patients who are persistently or recurrently febrile despite therapy with appropriate antibacterial agents are at high risk for the development of such infection. Two randomized clinical trials demonstrated that the empiric administration of amphotericin B to persistently or recurrently febrile granulocytopenic patients decreased the frequency, morbidity, and mortality of invasive fungal infection; these effects were especially marked in profoundly granulocytopenic patients who were not receiving antifungal prophylaxis. Current studies continue to indicate that prompt empiric administration of amphotericin B to persistently or recurrently febrile granulocytopenic patients ensures earlier treatment of deep mycoses. The roles of newer antifungal triazole compounds and of liposomal and lipid complexes of amphotericin B in empiric antifungal therapy must be investigated further in thoughtfully designed, randomized clinical trials. PMID- 1866557 TI - Relapsing systemic infection due to Rhodococcus equi in a drug abuser seropositive for human immunodeficiency virus. AB - A case of recurrent multisystemic infection due to Rhodococcus equi in a patient with antibody to the human immunodeficiency virus (HIV) but without AIDS is reported. This case, which occurred in a woman with a history of alcohol and drug abuse, is, to our knowledge, the first such case described. The infection involved the lungs, kidneys, brain, and bloodstream. Despite several courses of therapy with antibiotics to which her isolates of R. equi were susceptible in vitro, the patient experienced multiple relapses before her death. On the basis of this case and a few others reported in HIV-infected patients, we recommend an initial antibiotic course at least 6-8 weeks in duration, and we suggest that combination antibiotic treatment be considered. We also suggest that infection with R. equi be included in the diagnostic criteria for AIDS. PMID- 1866558 TI - Severe hypomagnesemia associated with pentamidine therapy. AB - A case of severe hypomagnesemia in a patient with AIDS that manifested as changes in mental status is presented. The hypomagnesemia was due to renal wasting of magnesium, most probably caused by pentamidine-induced renal tubular injury. This entity has been reported once before and should be considered in the differential diagnosis of altered mental status in patients with AIDS. PMID- 1866559 TI - An orthotopic heart transplant recipient with subacute meningitis. PMID- 1866560 TI - A morphogenetic study on host-pathogen interactions is needed for success in genetic analysis of microbial pathogenicity and the pathogenesis of infections. PMID- 1866561 TI - Clinical aspects of miliary tuberculosis in adults. PMID- 1866562 TI - Hypoprothrombinemia during therapy with cefotiam. PMID- 1866563 TI - Use of granulocyte-macrophage colony stimulating factor for treatment of drug induced agranulocytosis. PMID- 1866564 TI - Therapy for human brucellosis. PMID- 1866565 TI - Extrapulmonary infection with Pneumocystis carinii in patients receiving aerosolized pentamidine. PMID- 1866566 TI - Clostridium septicum bacteremia and diffuse spreading cellulitis of the head and neck in a leukemic patient. PMID- 1866567 TI - Rates of infectious disease consultations in hospitals of different sizes and types, 1986-1987. PMID- 1866568 TI - In memoriam: Vera La Verne Sutter. PMID- 1866570 TI - Binding of antibodies raised against tumour necrosis factor alpha (TNF alpha) to blood vessels and macrophages in inflamed synovial tissue. AB - The distribution of tumour necrosis factor alpha (TNF alpha) in rheumatoid synovium has been investigated. Ten rheumatoid synovia were compared with seven normal synovia and a range of other tissues, using one polyclonal and six monoclonal antibodies. A common staining pattern was obtained with five reagents. Absence of staining of tissue with the other reagents may relate to binding to different epitopes. Excluding cross-reactivity with smooth muscle seen with two reagents, results with the first five reagents were as follows. Normal tissues showed either no staining or faint staining of venular endothelium. In addition skin keratinocytes and colonic mucus showed staining. Rheumatoid synovium showed staining of venules and weaker staining of mononuclear cells, both as individual cells in the deep tissue and more uniformly in areas of the lining layer. The majority of cells that stained for TNF alpha double-stained for CD68 (macrophages). These represented less than 10% of CD68-positive cells. Isolated cells staining for TNF alpha stained for CD3 (T-cells), forming less than 1% of the total T-cells. The presence of staining of venular endothelium suggests that the cytokine may be synthesised by endothelial cells or may be taken up after production by macrophages. PMID- 1866571 TI - Serum IgE anti-cartilage collagen antibodies in rheumatoid patients. AB - The presence of circulating IgG, IgA and IgM antibodies to native cartilage collagens in some patients with rheumatoid arthritis (RA) suggests that an autoimmune response to cartilage collagens may be involved in the pathogenesis of RA. However, the relevance of such antibodies to the pathological process remains unclear, and it is likely that many humoral and cellular derived factors combined to trigger events leading to the chronicity of the rheumatoid lesion. Since histological and biochemical studies have suggested the involvement of mast cells in the rheumatoid joint, we have studied the frequency of IgE antibodies directed against the cartilage collagens type II, IX and XI in patients with active rheumatoid disease. Of the 91 patients' sera tested, 32 had significant levels of IgE anti-cartilage collagen antibodies when compared with non-arthritic controls. Total serum IgE levels did not correlate with the presence of IgE anti-collagen antibodies, nor were any patients positive for IgE antibodies to fibronectin, a widely distributed extracellular matrix component. These results are consistent with an allergic type I hypersensitivity reaction to cartilage antigens in RA involving mast cell and basophil degranulation. PMID- 1866569 TI - Diagnosis and pathogenesis of CNS lupus. AB - The central nervous system (CNS) is clinically involved in approximately 40% of all systemic lupus erythematosis (SLE) patients. Minor psychiatric symptoms and abnormalities on neuropsychological testing are being detected with increasing frequency. This review summarizes current thinking concerning the diagnosis and pathogenesis of CNS lupus. The main symptoms of CNS lupus can be diffuse (generalized seizures, psychosis) or focal (stroke, peripheral neuropathies). Neuropsychiatric symptoms often occur in the first year of SLE, but are rarely the presenting symptoms of the disease. In studies on the pathology of CNS lupus, vasculopathy, infarcts and haemorrhages are often observed, whereas vasculitis is rare. Endocardial lesions and mural thrombi have also been reported in 33-50% of CNS lupus patients. In diagnostic imaging of the CNS, magnetic resonance imaging (MRI) scans often provide evidence for edema or small infarcts, both in focal and diffuse CNS lupus, whereas computerized tomography (CT) scans only show gross abnormalities. The first reports on position emission tomography (PET) scans in CNS lupus patients show decreased glucose uptake in the brain. The cerebral blood flow decreases during active diffuse and focal CNS lupus. The blood-brain barrier is somewhat more frequently impaired in diffuse CNS lupus. Intrathecal IgG and IgM production is observed in 25-66% of all CNS lupus patient. Various specificities of autoantibodies have been observed in CNS lupus. Of these, anticardiolipin (ACA) antibodies show a well-documented association with focal involvement of the CNS in SLE. These antibodies could cause thrombosis by interfering with the protein C pathway of fibrinolysis. In addition, they are associated with endocardial and valvular heart disease, which is often observed in SLE and which could cause embolism. The relation between ACA and diffuse CNS lupus is not yet clear. Low-avidity anti-DNA antibodies are also found in CNS lupus, possibly because of their cross-reaction with cardiolipin. Antineuronal antibodies and lymphocytotoxic antibodies have been associated with diffuse CNS lupus and abnormalities on neuropsychological testing. However, the population of these antibodies is rather heterogeneous and it has not been possible to assess a common target antigen. Therefore, it is still obscure whether there is also a second immune-mediated mechanism responsible for the development of the diffuse form of CNS lupus. PMID- 1866572 TI - Bone loss in patients with rheumatoid arthritis--effect of steroids measured by low dose quantitative computed tomography. AB - For 2 years bone density changes in patients with rheumatoid arthritis were monitored to determine the effect of low dose corticosteroid treatment. Sixteen perimenopausal females were studied. Of these nine were treated with 5 to 20 mg prednisone per day and seven had no steroids. The differential effects on trabecular bone density and on cortical bone in the radius and the tibia were examined with high precision peripheral quantitative computed tomography (QCT). Steroid therapy did not influence cortical bone loss and had only a minor influence on trabecular bone density. Of greater importance was the influence of estrogen depletion. Corticosteroids and estrogen depletion, however, cannot explain fully the yearly loss of 5.7% in the trabecular and 4% in the cortical bone of the radius. PMID- 1866573 TI - Time sequence of coagulation data in patients with decompensated liver cirrhosis and suspected disseminated intravascular coagulation. AB - In patients with liver cirrhosis, especially in the advanced stage, the coexistence of low clotting factor levels, hypofibrinogenemia, thrombocytopenia and elevated fibrin(ogen) degradation product (FDP) and D-dimer levels may suggest the presence of disseminated intravascular coagulation (DIC). In this study we evaluated, in 21 patients with decompensated liver cirrhosis and elevated FDP and D-dimer levels, the time sequence of their coagulation data during a follow-up period of 15 days after the first observation; our aim was to clarify if these patients tend to develop during this time interval a severe consumption coagulopathy as an expression of overt DIC. We evaluated serum fibrinogen, platelet count, prothrombin activity, serum FDP and plasma D-dimer levels at days 1, 3, 6, 10 and 15. The coagulation data were fairly stable during the study period in all patients, even in the two patients who had upper digestive tract bleeding during the study time. Only two patients affected by infectious diseases showed a decrease of D-dimer and FDP levels after healing. Our data suggest that in decompensated liver cirrhosis the detection of elevated FDP and D-dimer levels is seldom related to the occurrence of an overt DIC, at least during a short time interval; in this condition heparin therapy seems therefore not advisable and even potentially dangerous. PMID- 1866574 TI - Alloantibodies in congenital von Willebrand's disease. AB - In a review of the literature published in 1984 we identified (from 13 kindreds) 15 patients with severe von Willebrand's disease (vWD) reported to have developed alloantibodies. In order to reexamine the problem, a questionnaire was sent in 1989 to 141 hemophilia centers in America and Europe; 101 answers were received. These dealt with a total number of 1,720 patients with vWD (all types) and 231 patients with severe (type III) vWD. Besides the 15 cases reported in 1984, 6 additional cases of anti-vWF alloantibodies were reported, i.e., one from Spain (a relative of a previously reported case), two from Venezuela (brother and sister) and three from North Carolina (unrelated patients). All these cases and those previously reported share the following features: occurrence of alloantibodies in multitransfused patients with severe vWD, poor clinical and laboratory response to replacement therapy with cryoprecipitate, inhibition of ristocetin-induced platelet aggregation. During the survey, an unusual antibody to FVIII:C with no reactivity towards vWF was reported in a multitransfused girl (from Tennessee) with type III vWD. It seems therefore that although the development of alloantibodies is a rare complication of severe vWD, due to its negative effect on the response to treatment it needs a prompt identification. PMID- 1866575 TI - Liver system. IV. More on the liver micro-unit: physics and geometry of its action. AB - The geometry of liver functional micro-units is described in the light of the immunohistologic features of human hepatocytes stained with a retinol-binding protein antibody. The stained cells were distributed into two ordered sets which provided a provisional representation of the law regulating both the motion and the alternation of the rest-work phases (homopoiesis and homorhesis configurations, respectively) which reflect bistable liver micro-unit equilibrium (auto-isodiasostasis). Oscillations between the HP and HR states generate a relaxation cycle that can be assumed to be shared by all micro-units and to be regulated by feedback mechanisms. A model illustrating the compactness of the liver's global action as a result of the activity of each micro-unit is also proposed. PMID- 1866576 TI - Liver system. V. Activation-extinction line of cyclic hepatocyte activities. AB - The excitation-extintion line of hepatocytes from an inert state towards the stabilization of a given activity is described. Within the cell, the switching on of any given activity is a competitive process among different activities. The process is driven by the influence field created in the environment of the Rappaport acinus by sinusoidal blood which changes its characteristics during its passage from the portal zone to the central vein. Every step of the excitation extintion pathway follows the so-called law of autoisodiasostasis (AIS), i.e. it is characterized by an oscillatory motion between restoring (homopoiesis or HP) and working (homeorhesis or HR) states. Since the cyclical bistable equilibrium of AIS characterizes all conditions of hepatocyte activities, the AIS cycle can be defined a limit cycle. PMID- 1866578 TI - TV nurses: sexy, deferential--and phony. PMID- 1866577 TI - The functioning liver mass. AB - The liver function results from the interaction of anatomical, histological and biochemical aspects. Thus the concept of functioning liver mass must be related to the many biological aspects involved in the process under evaluation, and its measure can be viewed as a virtual parameter averaging the liver function. In the present review the functioning liver mass has been categorized with respect to the many aspects involved (biochemical transformations, membrane transports and passive intraluminal transports) and their interactions (intracellular, transcellular, transacinar and flow-dependent). Parameters reflecting the functioning liver mass (whether static or dynamic) have been considered with respect to the experimental conditions and characterized according to the type of estimate they provide (capacity or activity). Methods for evaluating the functioning liver mass have been presented and discussed, and a protocol has been proposed for clinical applications, based on the association of the galactose elimination capacity measuring the metabolic mass with the hepatic clearance of D sorbitol evaluating the functional hepatic plasma flow. PMID- 1866579 TI - Treating AIDS patients and their loved ones with understanding. PMID- 1866580 TI - Volunteers help nurses tend boarder babies. PMID- 1866581 TI - How to make care plans work for you. PMID- 1866582 TI - When to suspect ectopic pregnancy. PMID- 1866583 TI - Elevated cholesterol. A nurse's guide to drug therapy. PMID- 1866584 TI - Pediatric trauma. When kids get hurt. PMID- 1866585 TI - Relaxation therapy works. PMID- 1866586 TI - Helping your patients dress for success. PMID- 1866587 TI - Your role in informed consent. PMID- 1866588 TI - Surgery, stress, and metabolism. PMID- 1866589 TI - Gastritis associated with infection by Helicobacter pylori in humans: geographical differences. AB - Previous studies have indicated that infection rates of Helicobacter pylori are influenced by geographical factors. The present studies evaluate the characteristics of gastritis, associated with infection by H. pyrlori, and demonstrate relationships between different geographical locations and the extent of inflammatory cell accumulation in the gastric mucosa. Gastric biopsy specimens were obtained from patients infected with H. pylori at three clinical sites (two from North America and one from South America). Gastric inflammation was evaluated by quantitative histomorphometric techniques. Patients from South America had a more severe gastritis than did those from North America. Additionally, in South American patients the neutrophil was the predominant inflammatory cell type in the gastric mucosa. In contrast, the lymphocyte was the primary cell composing the mucosal infiltrate of infected North American subjects. Eosinophil infiltration into the mucosa correlated with the extent of mucosal atrophy; however, there were no differences between the North and South American patient populations in the extent of mucosal atrophy present in the specimens. We conclude that the characteristics (severity and cell type) of gastritis associated with infection by H. pylori are influenced by geographical factors that may be similar to those that modify infection rates for different geographical locations. PMID- 1866590 TI - Clinical trials as etiologic research tools in Helicobacter-associated gastritis. AB - The role of clinical trials as tools to elucidate the etiology of chronic gastritis is discussed. Three areas are briefly explored. The first one concerns the classification of chronic gastritis, a constellation of interconnected nosologic entities. The second refers to the histopathologic factors of chronic gastritis; preliminary results show that clearance of Helicobacter pylori decreases the inflammatory infiltrate and suggest that H. pylori alters cell ploidy. The third area refers to the multifactorial etiology of chronic gastritis and the role that clinical trials could play in its elucidation. PMID- 1866591 TI - Molecular techniques for studying the epidemiology of infection by Helicobacter pylori. AB - The efficacy of one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of whole-cell protein patterns for fingerprinting isolates of Helicobacter pylori was assessed by means of computerized numerical analysis. Virtually all strains were found to have unique, stable, and reproducible protein profiles. The application of this technique to a collection of isolates from eight patients showed clearly that each harboured a distinct strain that was present before treatment and persisted after treatment. This suggests that relapse was due to recrudescence of the same strain rather than re infection with a different strain. Minor differences in protein banding profiles within sets of isolates from the same patient were evident, and this was confirmed by means of both two-dimensional PAGE protein patterns and restriction endonuclease analysis of DNA on the same strains. PMID- 1866592 TI - Relationship between gastric inflammatory response and symptoms in patients infected with Helicobacter pylori. AB - The relationship between the histologic severity of gastritis and associated symptoms was examined in 19 adult patients infected with Helicobacter pylori. At the time of gastrointestinal endoscopy, symptoms of dyspepsia were assessed by means of a linear analog scale. Gastric inflammation was quantitated with histomorphometric techniques. Symptoms such as epigastric pain, burping/belching, and nausea correlated with the degree of inflammation. These positive correlations suggest that the severity of the histologic gastritis contributes to the severity of symptoms. Therefore, utilization of a linear analog scale to assess symptoms may be a useful technique in evaluating the outcome of therapeutic trials of patients with symptomatic H. pylori infection. PMID- 1866593 TI - Gastric spiral bacilli in captive cheetahs. AB - Two kinds of gastric spiral bacilli were identified in the stomachs of captive cheetahs with naturally occurring gastritis. One type was morphologically similar to 'Gastrospirillum hominis'. This organism could not be cultured in vitro. Some of these bacteria had superficial helical filaments, and others did not. The other type was morphologically, biochemically, and bacteriologically similar to Helicobacter pylori. This organism is most likely a new species of Helicobacter. One or both of these bacteria may have been responsible for the gastritis seen in these cheetahs. PMID- 1866594 TI - Genomic variation in Helicobacter pylori: application to identification of strains. AB - DNA digest analysis, ribopatterns, and plasmid profiling were used to determine genomic variation in 55 strains of Helicobacter pylori from patients with gastritis in the USA, Peru, Australia, and the U.K. HaeIII-ribopatterns and total DNA digest patterns showed a high degree of heterogeneity, with at least 33 different genomic types among strains, including some sequential isolates. Plasmids, present in 51% of strains, were less useful as epidemiologic markers. Investigation of 14 multiple isolate sets showed that genotypic variants were present in pre- and post-treatment gastric mucosa, that relapse in some patients was due to reinfection by a genotypically different strain, and that the same strain persisted in most treatment failures. We conclude that molecular methods were excellent for precise identification of H. pylori, but ribopatterns had the advantages of reproducibility, high discrimination, and visual simplicity. PMID- 1866595 TI - Helicobacter pylori and progressive gastric pathology that predisposes to gastric cancer. AB - Evidence is presented suggesting that infection by Helicobacter pylori triggers and continuously contributes to the pathophysiology of progressive gastric changes that can ultimately lead to gastric cancer. In Peru, especially in population groups of low socioeconomic status, infection by H. pylori begins earlier in life and is more prevalent and persistent than in developed countries. The infection produces a destructive lesion of the mucinous surface epithelium which probably enables other aggressive luminal factors to cause further mucosal damage. As a consequence, active chronic gastritis appears. The gastritis is of the superficial type at the beginning but may progressively change to atrophic. Chronic atrophic gastritis is found more frequently and at a younger age in dyspeptic patients with low socioeconomic status--that is, in patients having higher prevalence of persistent infection by H. pylori since earlier in life. When chronic atrophic gastritis becomes severe and extensive, hypochlorhydria ensues. Hypochlorhydria favors the appearance of bacterial overgrowth, nitrites, and N-nitroso compounds in the gastric lumen. N-nitroso compounds, because of their mutagenic-carcinogenic properties, probably induce gastric premalignant lesions like intestinal metaplasia and dysplasia of the gastric mucosa. Oral bismuth therapy apparently reverses H. pylori-associated gastric dysplasia. It is proposed that future programs designed for the control of gastric cancer would be incomplete if they do not include further evaluation of the many effects of infection by H. pylori on the gastric mucosa and of cost-effective methods to eradicate the infection. PMID- 1866596 TI - Characterization of the morphologic conversion of Helicobacter pylori from bacillary to coccoid forms. AB - Growth studies of Helicobacter pylori were performed involving analysis of the bacterium and its microenvironment, to lend insight into the factors responsible for the morphologic conversion phenomenon. H. pylori converted from bacillary to coccoid forms in broth culture after incubation for 5 days under microaerobic conditions with agitation. This morphologic conversion was paralleled by a dramatic decrease in colony-forming units per milliliter (CFU/ml) and a significant endogenous increase in the pH of the broth culture. In addition, removal of broth cultures from microaerobic conditions after 3 days of incubation resulted in a rapid increase in culture pH, a morphologic conversion, and a concomitant decrease of CFU/ml. These observations suggest an inhibitory effect of basic pH, endogenously produced, on the growth of H. pylori in vitro. Experiments designed to identify the reason for the endogenous increase in culture pH demonstrated that the urease enzyme of H. pylori is not primarily responsible for this phenomenon. Rather, H. pylori appears to produce a deaminase enzyme that is likely responsible for the generation of ammonia, which results in the increase in culture pH, the morphologic conversion, and the loss of culturability observed in vitro. Also indicated is the need for a buffering component (for example, bicarbonate) to maintain pH conditions favorable to the growth of H. pylori. PMID- 1866597 TI - Factors affecting gastric mucosal hydrophobicity in man. AB - Contact angle measurements in animal studies have demonstrated that gastric mucosa has a relatively hydrophobic surface. We have developed and validated a technique for the measurement of this property on human endoscopic biopsy specimens. Mean contact angle of the gastric body (70 degrees) and antrum (70 degrees) was higher than the duodenal bulb (62 degrees; p less than 0.01) and distal duodenum (50 degrees; p less than 0.001). Subjects with duodenal ulcer and gastric ulcer had a lower contact angle than controls without ulcer (57 degrees, n = 49, and 59 degrees, n = 17 versus 66 degrees, n = 124, respectively). Helicobacter pylori infection was associated with reduced contact angle in subjects with gastritis (59 degrees versus 68 degrees). The contact angle was unchanged after treatment with ranitidine but increased to control values after clearance and eradication of H. pylori with bismuth and antibiotics. In postgastrectomy patients, the contact angle was reduced and correlated negatively with the bile acid content of gastric juice (r = 0.51, p less than 0.0001). We conclude that in man gastric mucosal hydrophobicity can be validly measured on endoscopic biopsy specimens and that it is high in health and reduced in bile reflux and in peptic ulcer disease, largely as a result of H. pylori infection. PMID- 1866598 TI - Helicobacter pylori stimulates pepsin secretion from isolated rabbit gastric glands. AB - In man, type-B gastritis caused by Helicobacter pylori has been associated with both increased serum pepsinogen in the presence of hypochlorhydria and increased levels of gastric pepsin. We investigated the effect of H. pylori on pepsinogen secretion in vitro and found that a sonicated preparation of H. pylori increased pepsinogen secretion from isolated rabbit gastric glands. This increase was significant after 5 min (p = 0.001), and maximum secretion was obtained after 30 min of incubation. The effect was additive to the secretion achieved by stimulation with carbachol at 10(-4) M plus 10(-4) isobutylmethylxanthine or 10( 8) M cholecystokinin. There was no detectable stimulation of pepsinogen synthesis by 2 h. Lactate dehydrogenase (LDH) release was assayed as an index of cell damage, and no significant LDH release was noted. The secretory factor in the H. pylori sonicate is inhibited by boiling, unaffected by heating at 60 degrees C for 30 min, dialysable, and inactivated by pronase. These data suggest that H. pylori stimulates pepsinogen secretion by a mechanism different from that of other tested stimulants. H. pylori-stimulated pepsinogen release may be a factor in the etiology of type-B gastritis and peptic ulcers. PMID- 1866599 TI - Loss of HLA heavy chain and beta 2-microglobulin in HLA negative tumours. AB - Expression of HLA class I antigens on the cell surface requires the association of heavy chain, endogenous peptide and beta 2-microglobulin (beta 2m). We have studied the expression of free class I heavy chain and beta 2m in cryostatic sections of 51 HLA class I negative human tumours of different origin. Selective low expression of beta 2m was observed only on the 9 colorectal adenocarcinomas. In contrast, simultaneous under-expression of heavy chain and beta 2m was detected in the rest of the tumours studied. Our results suggest that the accumulation in the cytoplasm of HLA heavy chain in HLA negative colorectal carcinomas is a particular mechanism that cannot be applied to all HLA negative tumours. PMID- 1866600 TI - Antigen processing and presentation by small and large B cells. AB - We have investigated the ability of different cells from non-immunized mice of the BALB/c strain to present antigen to two ovalbumin-specific I-Ad-restricted T hybridomas. Lipopolysaccharide-activated B-cell blasts were found to be the most efficient antigen-presenting cells. Purified small and dense splenic B cells also stimulated the hybridomas, although not to the same extent as the activated blasts, but comparable to non-fractionated spleen cells. Glutaraldehyde-treated B cells failed to present antigen, whereas F(ab')2 anti-mouse IgM-treated B cells exhibited markedly increased ability to present antigen. Using flow cytometry, we further purified the resting B cells by sorting the small lymphocytes to ensure that the ability of these cells to activate the hybridomas was not due to contamination with large non-resting B cells. The sorted small B cells retained the ability of antigen presentation. Their resting state was confirmed by the fact that they did not incorporate [3H]-thymidine as shown by autoradiographic analysis. PMID- 1866601 TI - Human MHC class I antigens are associated with a 90-kDa cell surface protein. AB - Human MHC class I proteins are expressed on almost all nucleated cells as a heavy chain (about 45 kDa) non-covalently associated with beta 2-microglobulin (12 kDa). In this report we show that MHC class I (MHC-I) proteins can also be associated with a 90-kDa protein in the cell membrane. Surface-radiolabelled cells were treated with dithiobis succinimidyl propionate (DSP) in order to preserve multimer protein complexes during cell lysis. The lysates were immunoprecipitated and analysed by SDS-PAGE and autoradiography. Immunoprecipitation of human MHC-I proteins co-precipitated another protein of about 90 kDa in molecular weight-p90. p90 was coprecipitated from all the MHC-I expressing cells tested: U937, Raji, Molt-4 and IFN-gamma treated K562, but not from untreated, MHC-I negative K562. A 90-kDa protein was also co-precipitated with MHC-I from fresh peripheral blood mononuclear cells (PBMC). Furthermore, p90 was coprecipitated by different MoAbs to the MHC-I heavy chain or beta 2 microglobulin, but not by control antibodies. Two additional co-precipitating proteins at 34 kDa and 28 kDa were seen in MHC-I precipitates from Raji cells. Our results suggest that MHC-I proteins and the 90-kDa protein are associated in the cell membrane, probably by a close but weak, non-covalent interaction. Two additional cell surface proteins at 34 kDa and 28 kDa seem to be MHC-I associated on Raji Burkitt's lymphoma cells. PMID- 1866602 TI - Lymphoproliferative responses to Plasmodium falciparum antigens in children with and without the sickle cell trait. AB - Blood mononuclear cells (BMNC) were isolated from sickle cell trait (HbAS) healthy donors and normal haemoglobin (HbAA) healthy donors resident in a P. falciparum endemic area of eastern Sudan. Blood samples were collected during the malaria season. BMNC were tested for their proliferative responses to phytohaemagglutinin (PHA), purified protein derivative of tuberculin (PPD) and to soluble P. falciparum antigens (SPAg). Higher responses to SPAg and PPD were observed in the HbAS children compared with the HbAA children, whereas no differences were observed among adults of the two phenotypes. Proliferative responses to PHA were comparable in all individuals tested. The significance of these findings in relation to haemoglobin phenotype, age and the possible immunoregulatory mechanisms operating in HbAS and HbAA children during the malaria season is discussed. PMID- 1866604 TI - [HIV transmission in hospitals and office practice. Protection of patients and medical personnel]. AB - Research has brought full knowledge of the identity of the human immunodeficiency virus (HIV) and its infective pathways. There are not enough diagnostic tools, however, to detect all HIV carriers in the first weeks and months after infection. This fact emphasizes that all patients should be assumed to be infectious for HIV and other bloodborne pathogens. A slight but certainly existent risk for all health-care workers is a reality. Information and recommendations concerning the protection of surgical personnel against acquisition of HIV while performing their duties, and protection of HIV carriers, were published in 1988 by the Union of Swiss Surgical Societies, Practicability and compliance with these infection-control precautions were checked in 1990 after two years' operation with the aid of a questionnaire. 89 valid answers from 110 Swiss hospitals (yielding a response rate of 81%), together with overall experience, allow us to evaluate the recommendations of 1988. We conclude that the risk of HIV infection after occupational exposure to blood and other body fluids, and the potential threat to the HIV carrier, can be minimized to a very high degree by acceptance of the recommended infection-control precautions. This is especially true in surgical units, emergencies and first aid. PMID- 1866603 TI - A novel form of CD4 (L3T4) mRNA in the murine fetal liver results in cell-surface expression of the L3T4 antigen. AB - The expression of the L3T4 antigen during ontogeny in the murine fetal liver has been investigated in parallel by northern blot analysis and cytofluorometry. The L3T4 gene is transcribed in the murine fetal liver in two polyadenylated mRNA species with the size of 3.5 kb and 3.7 kb. Whereas the 3.5-kb mRNA is expressed from days 13 to 18 of gestation, expression of the 3.7-kb mRNA is found only from days 16 to 18 of gestation and thus appears to be developmentally regulated. Immunofluorescent staining of fractionated fetal liver cells from days 12 to 18 of gestation with the anti-L3T4 antibody (GK1.5) provides evidence that cell surface expression of the L3T4 antigen on a subset of lympho-haematopoietic cells in the murine fetal liver is the product of a novel form of L3T4 mRNA with the size of 3.5 kb. PMID- 1866605 TI - [Vascular complications associated with aortic dissection]. AB - Aortic branch occlusion may constitute the mode of presentation or become an important focus of treatment in patients sustaining acute aortic dissection. The optimal therapeutic approach in patients with acute aortic dissection complicated by cerebral, visceral and peripheral vascular problems, and the implications of such complications, are not well established. We review the outcome in 187 consecutive patients (149 males and 38 females, mean age 58 years) with acute dissection of the thoracic aorta who were admitted and operated on in our department over a 13-year period. We assess the incidence, consequences and specific management of significant stenotic and obstructive lesions of the aorta and its branches. Noncardiac vascular complications occurred in 59 patients (32%); of these complications, 38 were associated with type A dissection (incidence 28%) and 21 with type B dissection (incidence 48%). A trend towards decreasing overall surgical mortality was observed in the second part of the study (1983-1989) compared with the first part (1977-1982) i.e. 28% versus 12%. Although aortic rupture and cardiac tamponade were the strongest correlate of morbidity and mortality, death specifically related to vascular complication was more common when such malperfusion occurred in the carotid, celio-mesenteric and renal circulation. Proximal aortic repair at the site of the intimal tear with obliteration of the false lumen may have restored adequate distal circulation in 27 patients in whom improvement of the visceral or peripheral ischemia was observed after the thoracic aortic repair. Additional procedures (immediately after the thoracic repair or later) were necessary in 15 patients to restore adequate perfusion in the compromised area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866606 TI - [Early mortality in surgery of rectal carcinoma]. AB - In a retrospective study (1984-1989) we analyzed 281 consecutive patients undergoing surgery for rectal cancer. We were interested in the relationship between operative mortality rate and type of operation as well as age and sex of the patient. We stress that "death within 30 days of the last operation" best reflects the true operative deaths. The mortality rate after different types of operation shows no significant differences. With increasing age and the associated increasing risk factors the mortality rate increases. In men a trend towards a higher mortality rate can be shown, but not to a significant degree. In our series the 30-day operative mortality was 1.4%, and the in-hospital mortality rate 3.9%. We recommended that death within 30 days of surgery should be the standard definition for operative mortality rate, since it offers the best yardstick for peri- and postoperative management. PMID- 1866607 TI - [Rhodococcus erythropolis infection in HIV-associated immunodeficiency]. AB - We report the first case in the literature of human infection with Rhodococcus erythropolis in an HIV-positive patient. A 24-year-old bisexual flight attendant had severe HIV-associated immunodeficiency with a CD4 cell count of 0.02 G/l. He complained of multiple subcutaneous nodules at different sites on the extremities. Biopsy of one node at his left knee revealed granulomatous inflammation filled with acid-fast rods. These bacteria were identified as Rhodococcus erythropolis. The disseminated infection was restricted to the skin and showed a slow response to long-term therapy with amoxicillin/clavulanic acid. No relapse has been observed more than 6 months after discontinuation of antibiotic therapy. The etiology of a concomitant polyarthritis remains unknown; a relationship with the rhodococcus infection is possible as the arthritis responded well to the antibiotic therapy and did not reactivate after discontinuation of antibiotics. Due to the difficult isolation technic, this pathogen may be overlooked in routine diagnostic procedures. The implications in clinical practice are discussed. PMID- 1866608 TI - [The etiopathogenesis of periodontal diseases: the role of microorganisms. A review]. AB - The microbiology of periodontal diseases as well as associations between certain microorganisms and types/stages of periodontal diseases are discussed and the ecology and the composition of the subgingival plaque are included in this discussion, too. Furthermore, the possible role of microorganisms associated with periodontal diseases, their pathogenic mechanisms and their virulence factors are treated in the present article. Periodic upsets of the host-parasite equilibrium seem to be responsible for the bursts of disease progression. Several plaque hypotheses (specific, non-specific, opportunistic) have been proposed as likely models to explain the nature of periodontal infections and diseases. However, none of these theories is widely accepted at the moment. Therefore, we suggest that further investigations concerning the complex bacterial interactions and the manner in which the host responds to the mass and the composition of the dental plaque must be carried out in the future. PMID- 1866609 TI - [The marginal adaptation of Cerec-Dicor-MGC restorations with dentin adhesives]. AB - Dicor MGC Cerec inlays were placed in 53 teeth clinically and in 24 extracted teeth. Both main groups were subdivided into the following four test subgroups: 1. monofunctional dentin adhesive without linings. 2. bifunctional dentin adhesive without linings. 3. monofunctional dentin adhesive with linings. 4. bifunctional dentin adhesive with linings. The marginal adaptation of the occlusal surfaces of the restorations placed clinically was evaluated from replicas using the scanning electron microscope at x 200 magnification. In contrast, the marginal adaptation of all the restored enamel surfaces and the disto-cervical dentinal margins of the restorations placed in the extracted teeth were similarly evaluated. These margins were examined before and after thermomechanical stressing. The restorations were stressed 120,000 times at 300 cycles of 5-55-5 degrees C, chemically degraded by immersion in ethanol of 75% for 20 h and brushed for 30 min with a toothbrush at 1,96 N load. The in-vitro restorations were also subjected to dye penetration tests. The percent "excellent margin" recorded along the enamel-composite interface of the occlusal surfaces of the clinically placed restorations varied between 83.6 and 88.2%. The corresponding scores for the in-vitro specimens were at least 95% before and 90% after the thermomechanical and chemical stressing. The bifunctional dentin adhesive "Prisma Universal Bond 2" had a 93.6% "excellent margin" along the dentin-composite margin before stressing which decreased to 84.4% after stress. These scores were not significantly different. PMID- 1866610 TI - [Experimental research on the finishing and polishing of amalgam fillings]. AB - In an in-vitro study occlusal amalgam restorations were finished and polished with four different methods. The quality of the restorations were evaluated according to the surface homogeneity and marginal adaptation. Additionally, the loss of substance due to the finishing and polishing process was determined. The results can be summarized as follows: The use of carbide finishing burs in combination with silicon polishing instruments (method A) results in rather smooth surfaces with numerous defects in the marginal area. The maximum loss of substance was about 160 microns in the filling material and about 110 microns in the adjacent enamel. Diamond finishing burs (grain size 30 microns = method B; grain size 15 microns = method C) in combination with silicon polishing instruments lead to rougher surfaces. The marginal areas, however, showed less deficiencies compared with method A. The maximum loss of substance in the adjacent enamel was about 220 microns (method B) and about 200 microns (method C), respectively, and in the amalgam area about 200 microns (method B) and 90 microns (method C), respectively. When finishing and polishing was done with a brush and a polishing paste (method D), the surface homogeneity and marginal adaptation of the restorations showed poor results. However, the maximum loss of substance was strongly decreased compared with methods A, B and C to an average of about 40 microns in the adjacent enamel and to about 75 microns in the amalgam. In conclusion, the application of the finishing and polishing methods A, B and C leads to a higher quality of the amalgam restoration than that, which can be achieved by applying method D.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866611 TI - [The finishing of adhesive tooth-colored inlays made of composite and ceramic]. AB - The destruction potential of 4 different finishing and polishing systems was evaluated using 104 occlusal direct inlays made from composite and ceramic, respectively. An inhomogeneous microfilled composite, a fine particle hybrid composite, a glass ceramic and a fine porcelain were utilized as filling materials. Finishing diamonds, white stones, flexible discs and silicon rubber polishing cups were examined as finishing and polishing instruments. Replicas were examined using a scanning electron microscope (SEM) to reveal enamel, composite and inlay margin fractures. Results were described as percentages of perfect margin. The surface roughness of composite and ceramic blocks was measured by means of a profile meter after surface finishing and polishing with the instruments mentioned above. Except for the fine porcelain, the flexible disc finishing and polishing system provides constantly the best results with greater than or equal to 95% of excellent margin. Similar results were achieved by fine finishing diamonds only. The surface roughness was reduced significantly by the flexible discs and by silicon rubber polishers only. Finishing diamonds and flexible discs are the most suitable instruments for finishing and polishing of tooth-colored adhesive inlays. They are nondestructive against enamel, the inlay and the cement surfaces. PMID- 1866612 TI - [Modifications of coated anchorages. Repairs and modifications of the coated anchorages of partial and hybrid dentures]. PMID- 1866613 TI - [Light-cured denture resins. A description and assessment of the Triad System from the prosthetic viewpoint]. PMID- 1866614 TI - [Denture stomatitis]. PMID- 1866615 TI - [The teaching of periodontics: difficulties and expectations]. PMID- 1866616 TI - [The SSO--sense and purpose. Societe Suisse d'Odonto-Stomatologie]. PMID- 1866618 TI - [Implants: the technical aspects. Crown and bridge prostheses with 2-part ITI implants: the impression technic, models and stump preparation. Internationales Team fur Implantologie]. PMID- 1866617 TI - Episodic probing attachment loss versus pocket depth: bacterial morphotype associations. AB - Marginal periodontitis in humans is characterized by phases of clinical disease progression, which are interspersed between periods of quiescence. The purpose of the present study was to compare subgingival bacterial populations from periodontal sites undergoing episodic probing attachment loss with bacterial populations from non-progressing lesions. Probing depth and attachment levels were measured in 10 adult patients at baseline, and every 30 days thereafter for 10 months. Pairs of corresponding contralateral sites were identified where one site had lost probing attachment within the previous month (P) and the other site had not (C). Subgingival bacterial samples were obtained from these sites and analyzed using darkfield microscopy. Motile forms, spirochetes, curved and straight rods, filaments, coccoid cells, fusiforms, and the total number of bacteria were assessed. The results showed that median pocket depth and attachment change were statistically significantly greater in P-sites as compared to C-sites. There was no significant difference in bacterial populations between P- and C-sites (p greater than 0.15). Motile forms, spirochetes, and total number of bacteria were positively correlated with pocket depth in P-sites, while in C sites the same was true only for curved rods. These results suggest that darkfield microscopy of subgingival bacteria in humans represents primarily pocket depth. PMID- 1866619 TI - [Individualized coloring of the denture base. A virtually practice-ready method for the staining of the external denture surface]. PMID- 1866621 TI - ["We must be concerned for solidarity". Interview by Kurt Venner]. PMID- 1866620 TI - [Synoptic treatment planning for implant solutions (II)]. PMID- 1866623 TI - [The radiation protection law--dentists should and can help shape the performance requirements]. PMID- 1866622 TI - [The disposal of amalgam wastes via Cendres et Metaux in Biel is on the right path]. PMID- 1866624 TI - [Dentistry in Sweden. Interview by Staffan Olsson]. PMID- 1866625 TI - ["We should pause at the point of progress" (the Eastman Dental Center). Interview by Michel Perrier]. PMID- 1866627 TI - Proteinase-mediated cartilage degradation in osteoarthritis. AB - Osteoarthritis (OA) is a disease of complex etiology that results in articular cartilage breakdown. Current experimental evidence strongly suggests that proteinases may be involved in this loss of cartilage matrix. The present review summarizes the evidence for implicating proteinases in the etiopathogenesis of OA and suggests that blockade of proteinase activity may provide a rational basis for new therapeutic agents. PMID- 1866626 TI - Are cytokines involved in osteoarthritic pathophysiology? AB - The putative role and mechanism of action of cytokines in the progression of arthritic diseases such as osteoarthritis (OA) has received particular attention because of the important interaction between articular cartilage and synovium in the pathophysiology of the diseased state. Maintaining matrix homeostasis in the normal adult cartilage phenotype requires normal turnover of matrix components, principally collagen and proteoglycan. Chondrocytes and synovial fibroblasts are targeted, via specific cell-surface receptors, by cytokines like interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) to produce matrix proteases and to suppress the synthesis of collagen and proteoglycan. Thus, cytokines not only favor tissue destruction, but also inhibit tissue repair. A structurally heterogeneous group of factors capable of directly antagonizing cytokine action is described, which acts either by blocking cytokine-receptor binding, inhibiting local cytokine synthesis, or complexing the cytokine into an inactive form. Furthermore, many growth factors, such as transforming growth factor-beta (TGF beta), can counteract the net effect of cytokines by stimulating the synthesis of matrix components or natural inhibitors of cartilage degrading enzymes. PMID- 1866629 TI - Classification of disease: osteoarthritis. AB - Criteria for the classification of osteoarthritis (OA) have been developed to establish uniformity in the reporting of this disease. Different criteria sets were developed for OA of the knee, hand, and hip that can serve different investigative purposes. The use of checklists facilitates the use of the criteria sets. PMID- 1866628 TI - Quantitative imaging of osteoarthritis. AB - Plain-film radiography currently remains the mainstay of imaging for diagnosis and follow-up in osteoarthritis (OA). However, recent studies have questioned some aspects of its use, particularly the correlation between radiographically evident joint-space narrowing and articular cartilage loss. The results with imaging modalities such as magnetic resonance imaging and ultrasound suggest that these methods will allow accurate noninvasive definition of the structure of articular cartilage and other soft tissues of joints. Other modalities, including microfocal radiography and high-resolution computed tomography, can produce detailed images of trabecular structure and bony alterations in osteoarthritis. Improvements in image analysis and data manipulation, including three-dimensional reconstruction and digitized storage and measurement of images, will likely enable improved quantitative assessment of the abnormalities demonstrated by these techniques. One can hope that such developments will facilitate not only improved detection and definition of OA, but also better evaluation of the effectiveness of pharmacological and physical therapy in practice and in clinical trials. PMID- 1866630 TI - Indices of severity and disease activity for osteoarthritis. AB - Several indices have recently been constructed by rheumatologists for the assessment of clinical status in osteoarthritis of the extremities. These include the algofunctional indices for the hip and knee (Lequesne), the Western Ontario and McMasters Universities (WOMAC) index (Bellamy), patients and investigator's overall opinion (results of drug trials), global evaluation of change in handicap (self-assessment), and articular index of physical examination in nature (Doyle et al). Each of the above indices have been validated by their respective authors. Presently, we propose to further validate the disease-activity indices. PMID- 1866631 TI - [Compartment syndrome]. PMID- 1866632 TI - [Compartment syndrome. Definition, etiology, pathophysiology]. AB - A compartment syndrome is a condition in which increased pressure a confined fascial space causes decreased capillary blood flow and tissue function below a level necessary for viability. There are a variety of possible etiologies, such as increased compartment content (hematoma, edema, exertion, intoxication) and decreased compartment size (constrictive dressings and casts, closure of fascial defects). The pathophysiology of compartment syndrome is based on the arteriovenous gradient theory. The high pressure within the compartment leads to a decrease in the arteriovenous gradient, to a lowering of tissue PO2 and finally to a metabolic deficit. The tolerance of increased pressure by nerve and muscle is defined by the relationship of mean arterial pressure to tissue pressure and not by absolute tissue pressure. PMID- 1866633 TI - [Diagnosis of compartment syndrome]. AB - Clinical diagnosis remains the most important factor in the diagnosis of compartment syndrome. Parameters such as swelling, pain result from passive stretching, sensory disturbances, motor weakness and pulse rate should be carefully analysed and recorded using a checklist. As a compartment syndrome can already occur after 2 h but often not until 6 days later, monitoring at short intervals is necessary during this time period. If the clinical diagnosis is not clear-cut and the possibilities of differential diagnosis have been exhausted, or if there is doubt concerning the extent of the increase in pressure, pressure should be measured to help establish the diagnosis. PMID- 1866634 TI - [Pathophysiology and pressure measurement in compartment syndrome]. AB - Traumatic or ischemic damage of the musculature and soft tissue may cause compartment syndrome. In trauma, mechanical influences provoke humeral disorders and liberation of vasoactive substances with early onset of compartment syndrome, but isolated total ischemia of more than 6 h is commonly followed after revascularization by compartment syndrome caused by post-ischemic dilation of vessels. An understanding of the pathophysiology in compartment syndrome provides a better possibility of predicting this severe complication in trauma and vascular surgery patients. Several techniques are described for intracompartmental pressure monitoring. In normotensive patients, an intracompartmental pressure of more than 40 mmHg indicates "apparent" compartment syndrome, while pressures between 30 mmHg and 40 mmHg are interpreted as "imminent" compartment syndrome. In these cases therapeutic/prophylactic dermatofasciotomy is necessary. In hypotensive patients the lower limit for conducting a dermatofasciotomy must be reduced. According to the pathophysiology, an intracompartmental pressure of about 30 mmHg for more than 6 h duration must be treated by dermatofasciotomy. PMID- 1866635 TI - [Compartment syndrome. Principles of therapy]. AB - Compartment syndrome can be classed as imminent, with moderate disturbances of muscular perfusion, no neurological symptoms and increasing tissue pressure, and manifest, with compromised circulation and loss of tissue function in the space and pathologic tissue pressure. When compartment syndrome is suspected, the most important immediate measure is wide splitting of any constricting dressings that have been applied. For decompression, the only adequate therapy, in imminent compartment syndrome, subcutaneous fasciotomy is required. The skin incision can be closed. Manifest compartment syndrome necessitates therapeutic fasciotomy, which means long incisions of skin and fascia, splitting of retinacula, excision of necrotic tissues, evacuation of hematoma and, if possible, rigid fixation of fractures. Skin closure is not permitted because of postoperative swelling, which can produce a rebound compartment syndrome. After 4-8 days edema decreases and the wound is closed by delayed sutures or a mesh graft. In the same session a second look operation for re-debridement of the tissues is done. Special problems arise in complex lesions of the foot, because of the thin layer of soft tissue coverage and the diminished blood supply to the bones of the foot. In the foot, decompression requires not only that the compartments of the short pedal muscles be opened, but also that the skin be adequately released. PMID- 1866636 TI - [Results of treatment of compartment syndrome of the upper arm]. AB - Only a small number of cases of compartment syndrome in the upper arm has been reported in the literature. The authors have reviewed 14 patients with 14 cases of compartment syndrome treated at their institution from 1980 to 1988. In the majority of cases in this series, compartment syndrome was caused by blunt, high energy trauma. There were 9 patients with multiple trauma, 7 of whom were motor cyclists, and fracture of the upper arm was present in most of these. In 5 patients scapulothoracic dissociation with disruption of the neurovascular bundle of the upper extremity concerned was present. In this series, 2 patients died of their injuries and three arms had to be amputated. At final follow-up after an average of 45 months (range 11-91 months) the functional result was dependent mainly on the severity of the associated injuries. Patients with isolated compartment syndrome had full recovery of upper limb function. PMID- 1866637 TI - [Compartment syndrome of the forearm]. AB - This paper reviews the etiology, clinical picture, treatment and follow-up in 25 patients treated for a forearm compartment syndrome at the medical school in Hanover. A volar-ulnar and, when indicated, a straight dorsal incision gave adequate decompression in all operatively treated patients. Follow-up examination revealed no damage or deficit that could be related to fasciotomy. Therefore, these results support the concept that operative treatment is widely indicated for forearm compartment syndrome. PMID- 1866638 TI - [Compartment syndrome of the hand. Diagnosis, therapy, results, late sequelae]. AB - Ischemic necrosis of the intrinsic muscles of the hand has been known about for decades, as has the resulting local ischemic contracture in the hand. As isolated compartment syndrome of the hand is a rare condition, this term has not yet become established. The etiopathology, diagnosis, therapy and results of treatment in 13 patients treated for compartment syndrome of the hand are presented. At the time of our follow-up study, 3 patients had died and 2 did not attend. In 1 patient the upper limb had meanwhile had to be amputated. Thus, late results were examined in 7 patients, but 2 of these had not recovered any hand function, as they had suffered a brachial plexus lesion on the affected side. In 5 patients the range of motion was unimpaired, but a slight loss of strength persisted in 4 patients and 1 patient complained of moderate paresthesia at the palmar scar. Despite the small number of patients, we feel that these results emphasize the need for early and adequate decompression in the case of compartment syndrome of the hand. PMID- 1866639 TI - [Compartment syndrome of the pelvis]. AB - In the pelvic region three major compartments (gluteus medius-minimus, gluteus maximus and iliopsoas) can be distinguished from the smaller compartment of the tensor fasciae latae muscle. Pelvic compartment syndromes are rare. A clear history of trauma is often lacking. Association with drug and alcohol abuse is common as well as an association with the widespread use of anticoagulant therapy. From 1982 to 1988 six acute buttock compartment syndromes were treated in the Trauma Department of Hannover Medical School. In five patients fasciotomy of the gluteal compartment was performed. Two patients with a compartment syndrome secondary to necrotising fasciitis died of septic multiple organ failure. The mean follow-up of the four other patients was 29 months (7-48 months). Three of these four patients revealed a decrease of gluteal muscle volume. Ergometric tests showed a decrease in gluteal muscle strength in all patients. PMID- 1866640 TI - [Compartment syndrome of the thigh]. AB - Compartment syndrome in the thigh is an uncommon condition. Most of the patients have multiple injuries. The main etiological factors are ipsilateral fractures of the femur and isolated severe soft-tissue injuries following blunt trauma. If the diagnosis is made clinically, compartment syndrome is treated by lateral incision of the thigh with incision of the fascia lata and the lateral intermuscular septum. Dermatofasciotomy does not lead to severe complications. In the follow-up there is no functional loss or neurological deficit. The indications for decompressive fasciotomy should be broad. PMID- 1866641 TI - [Compartment syndrome in popliteal artery injury]. AB - Between 1973 and 1988 50 patients with injuries of the popliteal artery were treated at the Medical School of Hannover University. While 26 patients with dislocations of the knee joint had mild soft tissue injuries, most of the 24 patients with periarticular fractures of the tibia and/or femur showed excessive soft tissue damage. In both groups 11 patients who were admitted with prolonged ischemia had to undergo amputations. Primary amputations were performed according to the recommendations of. The mean duration of ischemia was 5.5 h (range 2.2-9 h) in patients with knee dislocations (n = 21); fasciotomy was performed in 14 patients (67%). In patients with popliteal artery injuries combined with fractures (n = 18) the average duration of ischemia was 6.5 h (3-13.5 h); in 16 cases in this group (89%) fasciotomy had to be performed. Fasciotomy was always necessary in patients with combined injuries of the popliteal vein and artery. Moreover, all patients with ischemia of more than 6 h duration required fasciotomy. It can be concluded that fasciotomy will probably be necessary in patients with injuries of the popliteal artery and (a) severe soft tissue damage of the thigh and/or lower leg with compartment pressure of more than 30 mmHg; (b) ischemia of more than 6 h duration; (c) combined injuries of the popliteal vein and artery; (d) reconstruction of severely injured extremities. In general, fasciotomy should always be considered after reconstruction of the popliteal artery. PMID- 1866642 TI - [Compartment syndrome of the lower leg. Long-term results]. AB - An analysis of 134 surgically treated compartment syndromes of the lower leg was combined with a long-term follow-up concerning late sequelae. Direct trauma including simple closed as well as severely comminuted open fractures of the tibia and fibula were predisposing factors for the development of a compartment syndrome. Clinical symptoms led to the correct diagnosis, supported by intracompartmental pressure measurements. A unilateral parafibular dermatofasciotomy involving opening all four compartments was the therapy of choice. Fifty-nine per cent of the patients had no late sequelae at the 4.2 year follow-up. 12% poor results were characterized by loss of function and neurological deficits. This group included 8 amputations above the knee due to ischemic/infectious muscle necrosis. The time interval between trauma and operation was found to be the main contributing factor to the poor results, with a delay of 23 h due to secondary referral of the patients. Fasciotomy per se showed only minimal morbidity and is strongly recommended as an emergency procedure. PMID- 1866643 TI - [Functional rehabilitation of the upper extremity after compartment syndrome]. AB - In established compartment syndrome discrimination between the different forms of flexion contracture, i.e., manifest Volkmann's contracture and intrinsic contracture is necessary. A combination of both is also possible. Classification is essential for determination of whether reconstruction is indicated and what procedure should be selected. Shortening osteotomies of the ulna and radius are now of historical interest only, as is carpalectomy. Lengthening of the flexor tendons is indicated only in mild and localized limited contracture of only some of the long fingers, but there is a danger of possible further adhesions limiting the range of motion. Thus, cases of stage I and II according to Tsuge with persisting partial flexor motor function are treated mainly by muscle sliding operation (Scaglietti) combined with microsurgery for internal neurolysis of the median and ulnar nerves. The latter is anteriorly transposed. In cases of solitary intrinsic contracture we prefer the Littler release procedure. The most useful repair in advanced compartment syndrome, however, consists in free microsurgical tissue transfer. The non-contractile, degenerated scarred flexor muscle remnants are excised and substituted orthotopic by transfer of free, neurovascular muscle, with salvage of flexor motor function in the forearm. PMID- 1866644 TI - [The use of imaging techniques in the diagnosis of deep venous thrombosis of the legs]. PMID- 1866645 TI - [Current status of embolization materials]. PMID- 1866646 TI - [Methods relevant to the determination of bone mineral content]. PMID- 1866647 TI - [Current status of knowledge of the effects of uniform magnetic fields on biological systems during MRI studies]. PMID- 1866648 TI - [Joy and a fulfilled existence--also for people with and after cancer? Reflections on the role of the therapist and helper]. PMID- 1866649 TI - [Iron deficiency dyserythropoiesis in patients with chronic gastrointestinal and gynecologic hemorrhages. Study of 39 cases]. AB - A defect of haemoglobin synthesis is the classically recognized mechanism affecting the erythron functionalism in chronic iron deficiency. The poor erythroblastic bone-marrow response, plus a number of dyserythropoietic nuclear features, have led to think of an impairment of the cell cycle of erythroblasts in iron-lack anaemia. The aim of the present work was to study such hypothesis, not proven so far. Ten subjects with normal haemopoiesis and 39 patients with iron-lack anaemia of different aetiologies (namely, 19 with digestive tract bleeding, 16 with gynaecological bleeding, and 4 with haemorrhages on other locations) were included in a previously reported protocol. The scheme of such protocol consisted of: 1) bone-marrow erythroblast quantification; 2) analysis of their maturation gradient; 3) erythroblast mitotic index; 4) measure of the mitotic time in bone-marrow culture; 5) tritiated-thymidine incorporation to short-term bone-marrow culture and quantification of the erythroblastic labelling index. To these were added the degree of nuclear dyserythropoiesis according to Hill and Lewis, and the reticulocyte production index. The following mean values were found in the control group: erythroblasts, 25.5 (+/- 3.63) %; E1-E4, 47.66 (+/- 3.09) %; IDN, 0.67 (+/- 0.27); MI, 2.82 (+/- 0.66) %; MT, 1.05 (+/- 0.15 hr); LI, 34.88 (+/- 5.82) %. The mean values found in iron-lack anaemias were as follows: erythroblasts 39.42 (+/- 9.1) %; E1-E4, 42.25 (+/- 4.11) %; IDN, 7.77 (+/- 4.69); MT, 1.81 (+/- 0.95) hr; LI, 13.08 (+/- 6.51) %. The statistical analysis (Student's t) showed highly significant differences (p less than 0.001) in the increased IDN and decreased MI and LI in iron deficiency patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866650 TI - [Molecular analysis in 23 patients with T-lymphomas]. AB - Gene rearrangement analysis has been performed in 23 patients with T-cell lymphoproliferative diseases: 4 cases with T-gamma lymphocytosis, one case of a Sezary's syndrome, one case of T-cell angioimmunoblastic lymphoma, two cases of T cell lymphoepitheloid lymphoma, 11 patients with T-cell pleomorphic lymphoma, 3 cases of large anaplastic T-cell lymphoma and one case of T-cell lymphoblastic lymphoma. Rearranged banding patterns have been observed for at least one of the T-cell receptors (TCR) in 19 of the cases, and germ line configuration of the TCR and Ig genes in the other four. Likewise, both Ig and TCR rearrangements have been observed in three cases (one case of T-cell pleomorphic lymphoma, one case of large anaplastic T-cell lymphoma and one case of T-cell lymphoblastic lymphoma). Molecular genetic techniques have been used in order to direct monoclonal proliferations of T cell in the tumoral tissues, to determine the T- or B-cell lineage of the neoplasia and also to outline the molecular characteristics of each group that constitutes the complex classification of T cell malignancies. PMID- 1866651 TI - [Plasma and erythrocyte changes produced after running a marathon]. PMID- 1866652 TI - [Variant hairy-cell leukemia: immunophenotypic and ultrastructural study of a case]. AB - The recent introduction of new methods to identify different lymphocytic subsets has made it possible to recognise a rare variant of the classic hairy cell leukaemia, showing intermediate features between prolymphocytic leukaemia and hairy cell leukaemia. A 37-year-old patient is reported who followed a mildly aggressive clinical course and had massive splenomegaly without lymph node enlargement. Moderate leucopenia with lymphocytosis was present, with frequent hairy cells carrying one prominent nucleole. The cytochemical pattern include tartrate-sensitive acid phosphatase positivity, and the immunophenotype of such cells was CD22++, CD11++, CD24-, CD25-, CD2-, CD5-, CD19++. No lamellar ribosomal complex was seen in the ultrastructural study of the hairy cells. The patient was diagnosed as having variant hairy cell leukaemia and achieved partial response after splenectomy. The clinical, diagnostic and therapeutic aspects of this rare variant are discussed. PMID- 1866653 TI - [Rhino-cerebral mucormycosis and hematological neoplasia]. AB - Mucormycosis is a rare infection that occurs in immunocompromised patients. The rhinocerebral form presents in diabetics as a severe necrotizing sinusitis and is not frequent in patients with haematologic malignancies. Diagnosis requires direct examination and culture of biopsy specimens. Two patients with rhinocerebral mucormycosis and haematologic neoplasms (Non-Hodgkin's lymphoma and acute myeloblastic leukaemia) are described. Both patients had severe drug induced neutropenia when the infection appeared. One patient died in spite of aggressive treatment with surgery and amphotericin. PMID- 1866654 TI - [Importance of the determination of thrombin-antithrombin-III complexes in hypercoagulability states]. PMID- 1866655 TI - [Late recurrences in Hodgkin's disease: description of a case after 14 yr of continuous remission]. PMID- 1866656 TI - [IgM cryoagglutinin with biphasic hemolysin activity in a patient with AIDS]. PMID- 1866657 TI - [Bioethics and bio-rights in specialty programs]. PMID- 1866658 TI - [Serum ferritin as a possible indicator of regeneration in bone marrow transplantation]. PMID- 1866659 TI - [Pathological rupture of the spleen in a case of chronic myelomonocytic leukemia]. PMID- 1866660 TI - [Extra-osseous plasmacytoma in the breast]. PMID- 1866661 TI - [Relationship between surface HLA-DR expression and NBT reduction in monocytes in patients with colorectal cancer]. AB - The expression of HLA-DR antigens and their capacity to reduce nitroblue tetrazolium (NBT) have been evaluated in monocytes (Mo) from 28 patients with colorectal carcinoma (CCa) before antineoplastic treatment as well as in 29 normal control (NC). Simultaneously, circulating immune complexes (CIC) levels were studied in both groups. The results were expressed as the media of percentages. They show a decrease of Mo bearing HLA-DR (p less than 0.001 vs NC) and increase of MO with capacity to reduce NBT (p less than 0.001 vs NC). An increase of CIC levels in CCa compared to the NC (p less than 0.001) was also observed. We can postulate that the decrease in HLA-DR expression could be caused by the increase of toxic oxygen intermediates whose production was induced by CIC or tumoral antigens adherence. PMID- 1866662 TI - Comparison of mastectomy and lumpectomy for medial carcinoma of the breast. AB - The recurrence and five year disease-free survival rates of 86 patients with carcinoma of the breast located in the medial quadrants who had either lumpectomy and radiotherapy or mastectomy were compared. Patients who had lumpectomy and mastectomy were comparable with respect to variables reflecting extent of the disease. One of 54 patients who had lumpectomy had a local recurrence and five had a recurrence regionally or at distant sites. In the group of 32 patients who had a mastectomy, one patient had a local recurrence and an additional four patients had a recurrence at other sites. The five year study disease-free survival rate was 83 per cent for the lumpectomy group and 78 per cent for the mastectomy group. These data suggest that, for medial quadrant lesions, there may be a disease-free survival advantage associated with lumpectomy and radiotherapy over mastectomy. Further study of this treatment modality for this subset of patients seems indicated. PMID- 1866663 TI - Early surgical management of extensive gynecologic ureteral injuries. AB - Early ureteral reconstruction was performed during the immediate postoperative period upon 12 patients who sustained ureteral injuries secondary to gynecologic surgical procedures. The injuries occurred postoperatively for benign disease: endometriosis in one patient, fibrosis in eight patients and tubo-ovarian abscess in one patient. In three instances, portions of the ureter were noted in the pathologic specimen. After unsuccessful attempts at retrograde catheterization or stenting, all ureteral injuries were explored within three weeks of the primary gynecologic operation. Ureteral reconstruction was successful in all. The advantages of early operative intervention versus endoscopic or delayed operative intervention, or both, are discussed. PMID- 1866664 TI - Intestinal injury after lumbar discectomy. AB - In a review of 5,200 lumbar discectomies performed from 1974 to 1989, two patients sustained a ventral perforation of the disc space followed by isolated small intestinal injury. Both patients underwent lumbar discectomy at the lumbosacral junction and presented with signs and symptoms of acute abdominal distress within three days after the operation. At surgical laparotomy, small tears were noted in the ileum, which were closed primarily. The patients had an uneventful recovery. The results of a review of 11 instances reported in the literature suggest that isolated intestinal injuries usually occur postoperatively at the lumbosacral junction and involve the small intestine. Factors, such as body habitus, surgical experience, patient positioning and types of instruments, as well as the use of a surgical microscope, do not appear to modify the risk of intestinal injury. After discectomy, patients may present with acute abdominal signs and symptoms or chronic wound infections. Work-up studies include evaluation of vascular structures and ureters either roentgenographically or at abdominal exploration. A high index of suspicion and adequate disc space visualization during discectomy may reduce the incidence of this complication. PMID- 1866665 TI - Selective antibiotic prophylaxis in biliary tract operations. AB - A prospective study of 397 patients with primary biliary operations performed for benign disease included a perioperative culture of the bile. Two main groups of patients in whom bacteria in the bile and, thus, probably increased risk postoperative infection was common, are patients undergoing emergency operation (60 per cent bacteria in the bile, as compared with 22 per cent in those with elective operations) and patients with a history of acute cholecystitis or pancreatitis, or both, or jaundice (49 per cent bacteria in the bile with a positive history as compared with 11 per cent without). The rate of infection was 2.8 per cent in high-risk groups, as compared with 0.6 per cent in patients undergoing elective operative procedures with no history of acute cholecystitis, pancreatitis or jaundice. Thus, antibiotics can probably be reserved for those patients who had emergency surgical treatment and for those with elective operations and a history of acute cholecystitis, pancreatitis or jaundice. In addition, antibiotic prophylaxis might be indicated for all patients who are 75 years of age or older, as bacteria in the bile seems to be common in this age group even without a history of the aforementioned complications. PMID- 1866666 TI - The use of absorbable staples for construction of a bladder tube. AB - Stapling instruments have been widely used in general surgery but not in the surgical treatment of the urinary tract. The stapler Poly CS-57 (Auto Suture, U. S. S. C.) with absorbable staples has been evaluated in the construction of ten bladder tubes for ureteral substitution in three dogs and six pigs. The dogs and pigs were sacrificed at two, three and six months. There was no mortality rate, no infections, no suture leakages and no crystal or stone formation. There were three instances of ureterovesical anastomotic stenosis. It appears that the absorbable staple can be safely used in urologic operations and that the use of the Poly CS 57 stapler for the construction of a bladder tube makes the procedure safer, simpler and faster. PMID- 1866667 TI - The risk of ligation of the left renal vein in resection of the abdominal aortic aneurysm. AB - The left renal vein can be ligated during aortic operation to attain better access to the perirenal aorta. This maneuver has been considered safe, with a low incidence of postoperative renal complications. This study was done to evaluate the risk of left renal vein ligation and its influence on renal function in patients with elective resection of abdominal aortic aneurysms. The records of 332 patients undergoing elective repair of abdominal aortic aneurysms during a five year period were reviewed. The clinical and operative data of patients who had left renal vein ligation and those who did not were similar. Left renal vein ligation was not associated with an increased mortality rate but was strongly associated with an increase in serum creatinine level and a clinical diagnosis of postoperative azotemia. Nine of 13 patients who had left renal vein ligation had postoperative azotemia compared with 21 of 319 patients without left renal vein ligation (p less than 0.001). The mean change of preoperative and postoperative creatinine value was an increase of 1.92 milligrams per deciliter in patients with left renal vein ligation in contrast with 0.26 milligram per deciliter in patients without ligation (p less than 0.00075). Thus, ligation of the left renal vein increases the risk of postoperative renal complications and its use should be selective. PMID- 1866668 TI - An evaluation of multiple clinical variables for hypoxia during colonoscopy. AB - One hundred consecutive patients undergoing routine colonoscopy were evaluated for changes in arterial oxygen saturation levels. All of the patients were monitored with the Nellcor N-200 pulse oximeter (Nellcor Incorporated) by finger probe and received supplemental oxygen when SaO2 levels decreased below 90 per cent. Forty patients demonstrated a decrease in SaO2 to less than 90 per cent after intravenous sedation but prior to colonoscopy, 14 patients demonstrated a decrease in SaO2 to less than 90 per cent during colonoscopy, and 46 patients maintained SaO2 levels greater than 90 per cent at all times. No statistical differences were found when these three groups were compared for age, body surface area, drug dosage, smoking history and a history of pre-existing hypertension, diabetes, arrhythmias, angina or myocardial infarction and pulmonary disease. These data indicate that all patients undergoing colonoscopy should be placed on supplemental oxygen. We further recommend continuous cardiac and pulse oximetry monitoring when available. PMID- 1866669 TI - Intrathecal phenol rhizotomy for management of pain in recurrent unresectable carcinoma of the rectum. AB - The medical records of 11 patients with recurrent unresectable adenocarcinoma of the rectum who had intrathecal phenol block for the management of intractable pain were reviewed. There were seven patients with pelvic and four with combined pelvic and perineal recurrences. Five patients had sacral involvement by tumor. Six patients had received prior irradiation. Three patients had good, three had fair and five patients had poor results after phenol rhizotomy. Patients with good results had relief for a median of three months. The over-all survival rate after phenol injection was three months. Phenol rhizotomy is indicated for the relief of intractable pain secondary to recurrent unresectable carcinoma of the rectum in carefully selected patients. PMID- 1866670 TI - The Sugiura procedure for patients with hemorrhagic portal hypertension secondary to extrahepatic portal vein thrombosis. AB - The Sugiura procedure (SP) was performed upon 27 patients with hemorrhagic portal hypertension secondary to extrahepatic portal vein thrombosis (EPVT) without associated hepatic disease. There were 14 female and 13 male patients. The mean age was 28 +/- 14 years. The causes of EPVT were protein C deficiency in two; antithrombin III deficiency in one patient, a history of omphalitis in two patients, a history of pancreatitis in one patient and idiopathy in 21 patients. The SP was completed in two surgical stages in 14 patients and in one stage in nine. There was one operative death. One patient had mild postoperative encephalopathy, and two patients rebled at long term follow-up study. Actuarial survival rate was 82 per cent at five and ten years. It is concluded that the SP is a good alternative for the management of hemorrhagic portal hypertension secondary to EPVT. PMID- 1866671 TI - Transduodenal exploration of the common bile duct in patients with nondilated ducts. AB - Exploration of the small common bile duct can be technically difficult and is associated with a significant risk of ductal injury or late stricture, or both. Transduodenal common duct exploration after sphincteroplasty (TCDE/S) is an alternative method of duct exploration that avoids choledochotomy. Cholecystectomy followed by TCDE/S was performed upon 28 patients with nondilated ducts and suspected choledocholithiasis. Common duct stones were retrieved in 17 patients. Failure to retrieve stones in the remaining 11 patients was attributed to either false-positive results of cholangiography, forceful passage of stones into the duodenum during the initial insertion of a Fogarty catheter through the cystic duct or a false-negative finding at duct exploration. There was no perioperative mortality. Two patients had asymptomatic postoperative hyperamylasemia. One patient had postoperative pancreatitis, hyperbilirubinemia and cholangitis that resolved with antibiotic therapy by the eighth postoperative day. Other complications included wound infection, delayed gastric emptying, pneumonia and otitis media. The over-all morbidity rate was 28.6 per cent. Long term follow-up was obtained in all 28 patients. All patients in the follow-up group are free of recurrent biliary tract disease. TCDE/S appears to be a safe and effective method of exploring the nondilated common bile duct. PMID- 1866672 TI - Hamartomas of the breast. AB - The clinical and pathologic findings of 17 hamartomas of the breast were studied. All neoplasms were evident as clinically and mammographically discrete masses. The pathologic findings were varied and included circumscribed fibrocystic disease, adenolipoma, fibroadenoma with fat and fibroadenoma with lobules. The heterologous elements identified were cartilage and smooth muscle. All lesions were treated by simple excision. In this study, four different microscopic patterns of hamartoma are described and the necessity for a close clinicopathologic correlation is pointed out in the diagnosis of this lesion. PMID- 1866673 TI - Ultrasound-guided pancreatotomy for opening the pancreatic duct. PMID- 1866674 TI - Reperitonealization of the lesser curve in proximal gastric vagotomy for duodenal ulcer. AB - Ninety-six consecutive patients were operated upon with proximal gastric vagotomy for duodenal ulcer at our department during the two year period 1976 to 1978. These patients were prospectively randomized into two groups, one of which (45 patients) had reperitonealization of the lesser curve. These two groups are compared herein. Reperitonealization of the lesser curve was without benefit on long term clinical results, ulcer recurrence rate and gastric acid secretion. None of the patients had perforation of the lesser curve. PMID- 1866675 TI - Yet another use for chest tubes. AB - A chest tube can be used to change a tracheostomy tube just as a Seldinger wire is used to change a central line. A good match for size is important. The flange should be cut off of the chest tube and the inspired oxygen should be increased. Positive pressure ventilation can be performed through the chest tube by the addition of an endotracheal tube adaptor at the cut off end. PMID- 1866676 TI - Migratory failed percutaneous endoscopic gastrostomy. PMID- 1866677 TI - A newer surgical approach for patent vitello-intestinal duct anomalies. AB - A newer, relatively quicker approach has been described for the treatment of patent VID. Its superior advantages over other approaches include better cosmetic results, is technically simpler and can be done using local anesthesia without an appreciable amount of blood loss. PMID- 1866678 TI - Bacterial translocation. AB - The phenomenon of bacterial translocation, the movement of viable indigenous microorganisms across the intestinal epithelial barrier, has been recognized for almost 100 years. At the present time, the precise mechanism of microbial transport is unknown. Active epithelial uptake and phagocyte-mediated transport have been proposed as likely explanations for the extraintestinal movement of bacteria to mesenteric lymph nodes and distant organ sites. Translocation has been proposed as the pivotal process associated with intestinal origin portal sepsis in seriously ill and immunocompromised patients. While several etiologic factors can be implicated in the pathogenesis of bacterial translocation, the present clinical implications are based almost solely on studies of dogs, rats and mice. Present investigations continue to suggest a causal relationship between intestinal mucosal integrity and infection by indigenous gastrointestinal bacteria. PMID- 1866679 TI - Entrapment of the popliteal artery. AB - Although entrapment of the popliteal artery is uncommon, it is an important cause of arterial insufficiency in younger patients. Accurate diagnosis depends on a high index of suspicion combined with dynamic noninvasive testing and "stress angiography." Although angiographic demonstration of medial deviation of the artery is diagnostic, absence of this finding does not exclude the diagnosis of entrapment of the popliteal artery. Positional angiography may be necessary in these instances. Surgical exploration should be performed by a posterior approach, since this facilitates identification of the precise anatomic variant while allowing easy arterial repair, if necessary. The condition of the popliteal popliteal artery must dictate the extent of the surgical procedure. If the popliteal artery is normal, then relief of the constricting lesion alone will suffice. If the artery appears diseased or is thrombosed, then myotomy and arterial reconstruction must be performed. This is best accomplished by bypass grafting using autogenous vein or artery. If thromboendarterectomy is used, the clinician can expect a higher percentage of acute postoperative thromboses. PMID- 1866680 TI - Compatibility of packed erythrocytes and Ringer's lactate solution. AB - Packed erythrocytes are frequently reconstituted with crystalloid during rapid infusion. Dilution of whole blood with calcium containing solutions, such as Ringer's lactate has been cautioned against, citing possible clot formation because of chelation of the citrate anticoagulant. We studied the compatibility of Ringer's lactate solution and citrate phosphate dextrose (CPD)-preserved packed erythrocytes to evaluate the safety of using Ringer's lactate solution as a diluent in the emergency setting. Aliquots of CPD-preserved packed erythrocytes were diluted with either Ringer's lactate or normal saline solutions in ratios between 5:1 to 1:20 (packed erythrocyte to crystalloid), incubated at room temperature or 37 degrees centigrade and examined for clot formation at intervals up to two hours. Although clotting occurred at dilutions of 1:1 (packed erythrocytes to Ringer's lactate solution) and beyond, no clot formation occurred in the clinically relevant dilutions between 5:1 and 2:1. Thirty-two additional units of CPD-preserved packed erythrocytes were diluted to hematocrit values of 35, 45, 55 or 65 per cent and passed through a 170 micron filter. Flow rates of packed erythrocytes diluted with Ringer's lactate and normal saline solutions were compared. There was no difference in flow rates between packed erythrocytes diluted with Ringer's lactate compared with normal saline solutions. Ringer's lactate solution can be safely used as a packed erythrocyte diluent in patients requiring rapid blood transfusions. PMID- 1866681 TI - Misconduct and fraud in research: social and legislative issues symposium of the Society of University Surgeons. AB - The symposium was concluded with a question and answer period, which served to clarify and further emphasize the aforementioned issues. Many concerns of coauthorship responsibilities, due process, and potential sanctions were discussed. Moral and ethical issues reflecting the extent of punishment, reporting of misconduct to hospitals and specialty boards, and the almost assured litigation and counter-litigation were approached with considerable apprehension and concern. Misconduct in science will clearly be monitored more closely than in the past. Increasing coauthorship responsibility, conscientious senior investigator supervision, and institutional cooperation will provide the framework to discourage dishonesty in science and encourage proper educational development of both young and established investigators in a milieu of scientific integrity. PMID- 1866682 TI - Descending thoracic aorta-splenic artery graft for occlusive disease of the celiac axis. AB - A new procedure is presented for the restoration of normal blood flow to the celiac axis in cases of orifice lesions of the celiac artery. The operation consists of inserting a graft between the descending thoracic aorta end-to-side and the divided splenic artery end-to-end. PMID- 1866683 TI - Antiperistaltic and isoperistaltic intussusception associated with abnormal motility after Roux-en-Y gastric bypass: a case report. AB - Antiperistaltic and recurrent intussusceptions are extremely rare in the adult. We report a patient with both. The patient developed an antiperistaltic intussusception distal to her Roux enteroenterostomy years after a Roux-en-Y gastric bypass for morbid obesity. The diagnosis was made preoperatively with gastrointestinal contrast radiography and ultrasonography. At surgery, the intussusception was reduced, and 12 inches of nonviable bowel was resected, with a functional end-to-end anastomosis. An isoperistaltic intussusception occurred in the early postoperative period just distal to the anastomosis. Manometric evaluation of the Roux limb after the second operation showed altered gastrointestinal motility, consisting of orad-propagated and aboard-propagated migrating motor complexes, minimal phase 2 activity, and lack of conversion to the fed pattern with a liquid meal. Although manometry was not performed before the development of the intussusception, our findings are consistent with the hypothesis that altered intestinal motility may contribute to the development of intussusception. PMID- 1866684 TI - Transplantation of the right kidney: surgical technique revisited. AB - Transplantation of the right kidney with a short renal vein in a narrow pelvis with deep iliac vessels can be difficult and time-consuming. This technique requires minimal dissection, is fast and safe, and is now the author's preferred technique for transplantation of the right kidney. PMID- 1866685 TI - Vertical-banded gastroplasty in obesity. PMID- 1866686 TI - Endolymphatic antibiotic therapy. PMID- 1866687 TI - Cyclosporine and liver regeneration. PMID- 1866688 TI - Small-bowel obstruction by bladder catheter. PMID- 1866689 TI - Early burn excision and systemic response to endotoxin. PMID- 1866690 TI - Indicators of prognosis after hepatic resection for colorectal secondaries. AB - From 1960 to 1988, 266 patients underwent resection of colorectal secondaries to the liver with curative intent. All patients were followed until April 1, 1990, or death, with a median follow-up time of 52 months. Nine patients with minimal macroscopic residual disease and 38 patients with all gross tumor removed but positive margins showed a poor prognosis with a median survival time of 13.3 months, the longest being 42 months. Of the 219 patients having potentially curative resection, 12 patients died postoperatively (5.5%). Actuarial 5, 10 and 20-year survival for the remaining 207 patients was 39%, 28%, and 18%, respectively. At April 1, 1990, 77 patients were alive with no evidence of disease for up to 24 years, and 12 patients had died without recurrence. The following factors were associated with less favorable crude survival: presence and extent of mesenteric lymph node involvement (p = 0.0003), grade III/IV primary tumor (p = 0.035), synchronous diagnosis of metastases (p = 0.017), satellite metastases (p = 0.0003), limited resection margins (p = 0.019), and nonanatomic procedures (p = 0.013). With respect to disease-free survival, grading of the primary (p = 0.055) and the extent of clear margins (p = 0.019) failed to achieve statistical significance. Two other criteria are commonly recommended as absolute contraindications to hepatic resection: extrahepatic disease and the presence of four or more independent metastases. A radical excision of all detectable disease may rarely be possible in these circumstances. Nevertheless, within the curative settings, no significant predictive value regarding either overall or disease-free survival was found in this series. Three corresponding "high risk" patients are alive without disease at 5 to 11 years from hepatic resection. These patients with more advanced intrahepatic or concomitant limited extrahepatic disease require a particularly thorough diagnostic work up. As no superior therapeutic alternative is currently available, an aggressive surgical approach may occasionally be justified, and may, in a small portion, result in definite tumor control. PMID- 1866691 TI - Can infected prosthetic grafts be salvaged with rotational muscle flaps? AB - The conventional approach to prosthetic graft infection, including graft removal and extraanatomic reconstruction, conveys a substantial risk of limb loss and death and mandates more innovative solutions. From January 1985 to January 1989 eight rotational muscle flaps were performed on four men and three women with prosthetic graft infection who ranged in age from 42 to 79 years (mean, 67 years). The grafts involved included aortofemoral (three patients), femoropopliteal (two patients), femorofemoral (one patient), and subclavian carotid-carotid (one patient) and were composed of Dacron (five grafts) or polytetrafluorethylene (two grafts). Infections were in the groin in six patients and in the neck in the other patient; all patients had anastomotic exposure. Clinical presentations included abscess/purulent drainage (four patients), anastomotic hemorrhage (two patients), and anastomotic false aneurysm (one patient) and was associated with fever and/or leukocytosis in all patients. Positive bacterial cultures were obtained from all patients. Rotational muscle flaps performed included rectus abdominis (five grafts), pectoralis major (one graft), gracilis (one graft), tensor fascia lata (one graft); in two patients, rotational muscle flaps were performed after failed local sartorius muscle transfer. No major complications of the RMF procedures were encountered. One patient died 4 months after the operation of complications of ischemic colitis/perforation. The other six patients were discharged with completely healed wounds. One patient developed recurrent infection 12 months after the rotational muscle flap procedure; five (83%) patients have been followed for 12 to 51 months (mean, 27 months) without evidence of recurrent infection. These preliminary results suggest that rotational muscle flaps are a safe and effective treatment for prosthetic graft infection, even when local sartorius muscle coverage has failed. PMID- 1866692 TI - Superior vena cava and central venous reconstruction. AB - Partial or complete obstruction of the superior vena cava and its major tributaries occassionally results in incapacitating venous hypertension of the upper extremities and/or head and neck. Factors intrinsic and extrinsic to the central veins play a role in the pathogenesis. The more common causes include mechanically and chemically induced intimal injury with resultant fibrosis, sclerosis, or thrombosis and neoplastic masses with external compression or direct extension in the central venous structures. Medical therapy is indicated in the acute situation and generally allows the time necessary for development of collateral drainage routes. Persistent or progressive symptomatic venous hypertension develops in 5% to 40% of these patients, and approximately 10% of the patients will remain incapacitated. Presented here is a series of 10 patients who underwent reconstruction of the superior vena cava or central veins for incapacitating venous hypertension of the upper extremities and/or head and neck. Reconstruction was accomplished by venous transposition (three patients), externally reinforced ePTFE (six patients), and reversed saphenous vein graft (one patient). No perioperative deaths occurred; however, two late deaths occurred at 3 and 9 months after reconstruction from causes unrelated to the operative procedure. One patient experienced early postoperative graft thrombosis requiring thrombectomy, after which the graft remained patent. All patients had patent grafts and were asymptomatic with respect to their venous disease at the time of preparation of this manuscript, with a mean follow-up period of 30 months. Specific details concerning these 10 cases are discussed and integrated with a focused review of the literature and the historic development of the intraoperative techniques and postoperative care that facilitate the successful management of patients with symptomatic central venous occlusion. PMID- 1866693 TI - Superficial thrombophlebitis diagnosed by duplex scanning. AB - Since July 1982, this noninvasive vascular laboratory has performed 12,856 lower extermity venous duplex examinations. All cases of acute venous thrombosis have been categorized and entered into a computer data base. One thousand four hundred twelve examinations were positive for acute venous thrombosis. This report analyzes the laboratory's entire experience with superficial thrombophlebitis (SVT). One hundred eighty-six patients were diagnosed by duplex scanning to have SVT. Women outnumbered men 99 to 87. They were slightly older (average age 58.4 +/- 16.2 years) compared with the men (53.8 +/- 14.2 years). Men were more likely to have a complicated course of SVT (40% vs 22%; p less than 0.01). Complications included either radiographically documented pulmonary embolism or deep venous involvement. Fifty-seven (31%) patients had at least one complication of SVT. A series of predisposing factors was analyzed and six factors were associated with an increased risk of complications. They are bilateral SVT (p less than 0.01), age greater than 60 years (p less than 0.01), male sex (p less than 0.01), history of deep venous thrombosis (p less than 0.01), bed rest (p less than 0.02), and presence of infection (p less than 0.02). Location of thrombus within the greater saphenous vein (35%) was most likely to be associated with complications. Isolated varicosities (8%) were least likely to be associated with complications. Duplex scanning identifies a significant number of complications of patients with SVT and should be obtained in cases of saphenous vein involvement or in the presence of associated risk factors. PMID- 1866694 TI - Isotopic evaluation of the metabolism of pyruvate and related substrates in normal adult volunteers and severely burned children: effect of dichloroacetate and glucose infusion. AB - In this study we have assessed the hypothesis that there is a postreceptor defect in glucose metabolism that makes the severely burned patient unable to oxidize glucose efficiently as an energy source. The intracellular pyruvate pool was labeled by the infusion of 3-13C-lactate, and expired CO2 production and isotopic enrichment of both pyruvate and CO2 were determined to calculate the rate of pyruvate production and oxidation. 6,6-d2-Glucose and 15N-alanine were infused simultaneously to relate pyruvate kinetics and oxidation to glucose and alanine kinetics. Five normal volunteers and 10 severely burned patients (mean of 80% +/- 5% body surface burned) were studied in the basal state and during continuous (unlabeled) glucose infusion. Also, the effect of dichloroacetate, which normally stimulates pyruvate dehydrogenase activity, was assessed in both volunteers and patients. The burned patients had many of the classic metabolic responses to severe injury, including significant increases in resting energy expenditure, glucose production, and alanine release from protein breakdown. However, rather than being inhibited, the rate of pyruvate oxidation was increased approximately 300% in burned patients. Although the patients had an elevated mean concentration of lactate, stemming from increased lactate production, no deficit in pyruvate dehydrogenase activity was evident. Rather, the high rate of lactate production was apparently a consequence of the high rate of glycolysis. On the other hand, the direct pathway for synthesis of glycogen from infused glucose appeared to be impaired in burned patients. In both volunteers and patients, dichloroacetate stimulated the percent of pyruvate directed to oxidation, thereby reducing the conversion of pyruvate to other fates, including lactate. However, because there was no deficit in pyruvate dehydrogenase activity in the patients compared with normal volunteers before dichloroacetate treatment, no unique effect of dichloroacetate on glucose or protein kinetics was observed in burned patients. From these results we conclude that if there is a postreceptor defect in glucose metabolism in burned patients, it involves the pathway of direct glycogen synthesis and not the pathway of oxidation. PMID- 1866695 TI - Carcinoid tumors: the relationship between clinical presentation and the extent of disease. AB - In this study the relationship between the initial clinical presentation and the extent of tumor progression was determined in a group of 31 patients with carcinoid tumors. The proportion of patients with symptomatic tumors was similar to those patients with carcinoid tumors that were incidentally found (55% versus 45%; SE = 0.089). Symptoms were caused by metastatic tumor in nine (30%) of the patients and by local effects of the primary tumor in eight (26%) of the patients. The patients with symptoms had a significantly increased frequency of metastatic disease, even when the symptoms were due to the primary tumor, compared to patients with no symptoms (76% versus 7%; p less than 0.001). Tumor size was related to the presence of symptoms and metastases. Symptoms were most common when the size of the primary tumor was greater than 1.0 cm (p less than 0.005), although the rate of metastases increased when primary tumors were 2.0 cm and larger (p less than 0.01). These results indicate that the presence of symptoms or a primary tumor 2.0 cm or larger are associated with an increased risk of metastatic disease in patients with carcinoid tumors. These patients should be treated with wide resection of the primary tumor and its lymphatic drainage. PMID- 1866697 TI - Treatment of bilateral intrahepatic stones with high duct strictures through selective central hepatic resection. AB - Bilateral intrahepatic duct stones with strictures, more common in the Orient than elsewhere, are difficult to access surgically. The results of surgical procedures have not been generally successful and are attended by a high postoperative complication and recurrence rate. We report the treatment of 30 patients with intrahepatic calculi and high duct strictures by means of selective central hepatic resection without dissection of the major vessels at the hilum. Central hepatic resection provided satisfactory access to the primary and secondary confluences of the intrahepatic ducts, allowed removal of residual stones and ascariasis, and permitted correction of multiple strictures. Twenty nine patients so treated were followed for a mean of 32 months after operation. No patients developed recurrent fever, biliary colic, or jaundice after the operation. The technique is therefore recommended as an effective alternative to extensive hepatic lobectomy in the treatment of the intrahepatic calculi with multiple strictures. PMID- 1866696 TI - Hemodynamic effects of varied graft diameters in the venous system. AB - Both in vivo and mathematical models of venous hypertension were used to evaluate the hemodynamic effects of 4, 6, 8, and 10 mm diameter cross-femoral venous bypass grafts (CFBs). Eighteen grafts (length 138 +/- 3.4 mm) were tested in paired sequential fashion (four grafts, 4 and 8 mm; five grafts, 6 and 10 mm) in nine greyhounds (femoral vein diameter, 7.7 +/- 0.09 mm). Bilateral hindlimb venous pressures and flows were measured before and after unilateral iliofemoral venous ligation, 30 minutes after CFB insertion, and for 5 minutes after venous flow augmentation induced by stimulated muscle contraction. CFBs of all sizes were equally effective at relieving the occlusive venous hypertension at rest. Muscle contraction elevated venous pressure in all ligated hindlimbs (p less than 0.0001); however, the pressure returned to baseline by 3 minutes in dogs with 6, 8, and 10 mm grafts but remained elevated (p less than 0.05) with the 4 mm grafts even after 5 minutes. Peak graft flow (first 90 seconds after contraction) was significantly greater through the 8 mm grafts than through the 4 mm grafts (p less than 0.01), although no difference was noted in flow rates between 6 and 10 mm grafts. The pressure gradient across the graft as predicted by the mathematic model for 6 to 10 mm conduits was less than 5 mm Hg for flows up to 1000 ml/min, although the pressure gradient of the 4 mm graft exceeded 5 mm Hg at 200 ml/min and approached 30 mm Hg at 1000 ml/min. Therefore, data from both canine and mathematical models agreed that, at rates approximating human resting flow (1000 ml/min), no adverse short-term hemodynamic consequences result from CFB conduits of 6 to 10 mm diameter. PMID- 1866698 TI - Successful 20-hour rat liver preservation with chlorpromazine in sodium lactobionate sucrose solution. AB - We investigated the effect of the addition of chlorpromazine to a new, simplified organ preservation solution, sodium lactobionate sucrose (SLS), for 20-hour hypothermic rat liver preservation. Survival beyond 7 days after orthotopic transplantation of the stored liver was eight of eight rats in control groups (immediate transplantation, less than 1-hour preservation), one of 14 rats with the University of Wisconsin (UW) solution, four of 14 rats with SLS, seven of eight rats with SLS + chlorpromazine, 1 mg/L, and seven of eight rats with SLS + chlorpromazine, 10 mg/L. The differences is survival between UW and SLS and between SLS and SLS + chlorpromazine were significant (p less than 0.05). Lactic dehydrogenase levels in the effluent after reflushing through the portal vein at the time of transplantation were 145 +/- 20 IU/L (mean +/- SEM) in the controls, 525 +/- 78 IU/L in UW, 492 +/- 44 IU/L in SLS, 290 +/- 39 IU/L in SLS + chlorpromazine, 1 mg/L, 290 +/- 11 IU/L in SLS + chlorpromazine, 10 mg/L. The values for the SLS + chlorpromazine were significantly lower than for SLS and UW (p less than 0.05). The pH of the effluent was 7.10 +/- 0.10 in controls, 6.42 +/ 0.12 in UW, 6.64 +/- 0.18 in SLS, and 7.07 +/- 0.02 in SLS + chlorpromazine, 1 mg/L and 10 mg/L. The pH drop was significantly greater in the groups without chlorpromazine (p less than 0.01). This study shows that superior rat liver preservation was achieved with a simplified lactobionate solution containing sodium as the principal cation, sucrose in place of raffinose, and omitting the colloid and several of the other UW components. The addition of low concentrations of chlorpromazine further enhanced the effectiveness of this solution, without the need for donor pretreatment. PMID- 1866699 TI - The surgical management of superficial infections caused by atypical mycobacteria. AB - We have recently treated four patients with atypical mycobacterial skin infections. Two patients were infected with Mycobacterium smegmatis after self injection with a veterinary-grade anabolic steroid. To our knowledge, this complication has not been previously described. The other patients had steroid dependent asthma and lower extremity infections involving M. kansasii and M. chelonei after minor household trauma developed. Atypical mycobacterial skin infections may be seen as chronic ulcerations with violaceous edges, rolled margins, and significant subcutaneous necrosis. An indolent course and the clinical appearance may aid in diagnosis. In our experience, limited incision and drainage or dressing changes fail to eradicate these infections, even when accompanied by appropriate antibiotic therapy. Successful treatment requires aggressive debridement of all infected subcutaneous tissues and skin. Split thickness skin grafting was successfully used to cover large wounds. Grafting did not appear to foster recurrent infection. PMID- 1866700 TI - Hand-foot-and-mouth disease: report of a case in Texas. AB - Coxsackie virus infections are highly contagious and can occur at epidemic levels within low socioeconomic populations. Since these diseases spread by contact, summer and fall occurrences increase significantly. A low grade fever and malaise are often related to non-specific viral infections. Hand-foot-and mouth disease (HFMD) is specifically caused by coxsackie virus. PMID- 1866701 TI - Have you given a table clinic ... lately? AB - This short paper will give the reader the basic understanding of what a table clinic is and how to present one. The material is presented in a generalized format that is quick and easy to read. The intent is to stimulate interest among members of organized dentistry to present table clinics at the local, state and national levels. PMID- 1866702 TI - Associateships: trends and opportunities. AB - Interest in associateship dental practice arrangements has increased rapidly in recent years. Surveys by the American Association of Dental School indicate most new graduates who go directly into private practice are now doing so as associates. Although the percentage of Texas graduates planning to immediately enter solo private practice is higher than the national average, the trend toward associateship preference for the Texas graduate follows the same curve as the national average. Associateships can be rewarding, stimulating experiences and dentists who already own established practices should be aware that there are many well-educated young graduates seeking associateships. The Texas Dental Association has a well organized, systematized placement service (TDA Placement Service). Students review the Placement Service computer printout regularly, and practitioners seeking an associate should consider utilizing this same free listing service. PMID- 1866703 TI - Oral hygiene for dental implant patients. AB - Effective home care cleaning techniques are described for patients with dental implants. Specific methods are described for the fixed prosthesis, the fixed detachable prosthesis and the removable prosthesis. While dental caries is no longer a problem, peri-implant gingivitis and peri-implant osteitis are concerns for patients who have dental implants. Techniques and the tools available enable dental implant patients to keep their dental implants plaque-free and consequently, free of peri-implant infection. This report will discuss home care for the fixed detachable prosthesis, the removable prosthesis, and the fixed prosthesis. PMID- 1866704 TI - Amalgam and mercury toxicity: an update. PMID- 1866706 TI - If you don't have an office policy manual, you don't have a policy. PMID- 1866705 TI - The 1990 C.T. Rowland Award. Case report. PMID- 1866707 TI - Improvising care for conjoined twins in India. PMID- 1866708 TI - The effects of warfarin on HepG2 cells suggest that prothrombin and factor X interact differently with the vitamin K-dependent carboxylase in the secretory pathway. AB - HepG2 cells have been shown to respond to warfarin by 1) enhanced vitamin K dependent carboxylase activity; 2) enhanced intracellular concentration of the factor X clotting factor precursor and 3) enhanced vitamin K-dependent 14C labelling of a 74 kDa microsomal protein which has been identified as the factor X precursor. There was no difference in any of these measured parameters whether the cells had been treated for 4 or 24 hours with warfarin. In contrast to the intracellular factor X concentration, the intracellular prothrombin precursor concentration was not affected by the drug which suggests there is a difference in the mechanism of processing of these two clotting factors by HepG2 cells. The data are consistent with the view that warfarin maintains its effect on the vitamin K-dependent carboxylation system in HepG2 cells for 24 hours and support the hypothesis that clotting factor X and prothrombin precursors interact differently with the vitamin K-dependent carboxylase. PMID- 1866709 TI - Thromboxane and cysteinyl-leukotriene formation are differentially activated in spontaneously clotting whole human blood in vitro. AB - We have previously demonstrated that clotting of whole human blood in vitro not only triggers the production of thromboxane (TX) B2 but is also accompanied by formation of 5-lipoxygenase-derived cysteinyl-leukotrienes (LT). In order to further characterize the mechanisms leading to activation of the cysteinyl-LT production, we have now investigated the effects of thrombin on cysteinyl-LT as well as TXB2 formation in whole human blood. Addition of exogenous human alpha thrombin (0.1 - 3.0 U/ml) to whole human blood incubated in vitro led to a concentration- and time-dependently increased release of TXB2 into the serum samples. The serum contents of cysteinyl-LT were, however, not significantly affected. Inactivation of endogenously generated thrombin by inhibitors such as recombinant hirudin (HBW 023, 0.43 - 1.43 microM) or the peptidyl chloromethyl ketone, D-Phe-Pro-Arg-CH2Cl (1.0 - 100 microM) concentration- and time dependently inhibited the release of TXB2 into the serum or plasma samples. In contrast, however, serum contents of cysteinyl-LT remained unchanged. The identity of immunoreactive material was confirmed by thin-layer chromatography of immunoreactive TXB2 and by reversed phase HPLC of immunoreactive cysteinyl-LT. As expected, washed human platelets stimulated with alpha-thrombin were identified as the major source of TXB2 generation but purified monocytes were also found to release some TXB2 upon alpha-thrombin stimulation. Release of TXB2 by isolated human polymorphonuclear leukocytes (PMN) was negligible in the presence of this stimulus. None of the cells which are known to possess 5-lipoxygenase activity such as PMN or monocytes did release neither cysteinyl-LT nor LTB4 upon stimulation with human alpha-thrombin up to 10 U/ml. These data demonstrate that TXB2 production and cysteinyl-LT formation are differentially activated in spontaneously clotting whole human blood in vitro, the former being dependent on endogenously generated thrombin the latter being dependent on a stimulus yet to be identified. PMID- 1866710 TI - Acute carotid artery occlusive thrombosis and its pharmacological prevention in the rabbit. AB - A simple and reproducible method to induce an occlusive thrombus in rabbit carotid artery is reported. Rabbits were anesthetized and prepared to record arterial pressure, heart rate, and carotid blood flow. A critical stenosis of a damaged carotid artery was obtained using an external plastic cylinder. Complete occlusion occurred within 6 to 12 minutes, as measured by the decrease in blood flow. Both stenosis of the vessel and deliberate damage (clamping by surgical forceps) were found essential to occlusion. Occlusion was prevented by administration of heparin (200 IU/kg), tissue plasminogen activator (300 micrograms/kg), iloprost (10 micrograms/kg) or the synthetic thrombin inhibitor, FPRCH2Cl (0.5 mg/kg), while ASA (100 mg/kg) was uneffective. The procedure permits an easy and rapid evaluation of thrombus formation and of anti-thrombotic drugs affecting the hemostatic process. PMID- 1866711 TI - Malignant cell attachment to endothelium of ex vivo perfused human umbilical vein. Modulation by platelets, plasma and fibronectin. AB - The success of blood-born metastatic spread depends upon a key event: the tumor cell arrest and attachment to the host organ vasculature. In the present study, we have investigated interactions between several normal and cancer cell lines and vascular endothelium in a model of ex vivo perfusion of human umbilical vein. In this system, hydrodynamic parameters are monitored and endothelial cells are kept in their original environment known to modulate their phenotype. Metastatic tumor cell adhesion to the perfused endothelium was found to be significantly higher than that of normal cells tested. Platelets and soluble plasma factors including fibronectin promoted tumor cell arrest and adhesion to endothelium. Altogether our results indicate that the ex vivo perfusion of human umbilical vein allows the study of the interactions between malignant tumor cells, circulating plasma or blood cells and the endothelium during blood-born metastatic spread. PMID- 1866712 TI - Interaction between prostaglandin E1 and nitric oxide (NO). AB - A synergistic antiplatelet effect between prostaglandin I2 (PGI2), a cAMP stimulator, and nitric oxide (NO), a cGMP-stimulator, has been described. Data on a PGE1-NO interaction, however, are lacking so far. We therefore examined the question in healthy volunteers, whether a similar synergism exist between PGE1 and NO on human platelets in vitro. Each of the substances alone caused a dose dependent inhibition of ADP-induced platelet aggregation, PGE1 (1ng/mlPRP) reduced platelet aggregation by 27.8 +/- 14.6%, NO (0.3%) by 26.7 +/- 25.5%. The combination of these compounds caused an additive effect resulting in a reduction of 40.6 +/- 23.5%. The findings indicate that PGE1 (like PGI2) and NO have a synergistic antiplatelet action. The concomitant treatment with both compounds offers an interesting concept for clinical therapy. PMID- 1866713 TI - Effect of 13-hydroxyoctadeca-9,11-dienoic acid (13-HODE) on thrombin induced platelet adherence to endothelial cells in vitro. AB - The effect of exogenous 13-HODE on alpha-thrombin induced adherence of platelets to monolayers of cultured pulmonary artery endothelial cells was determined using homologous sheep cells. In a separate series of experiments, endogenous 13-HODE was demonstrated in sheep endothelial cells by reverse phase high pressure liquid chromatography. Levels of endogenous 13-HODE were decreased by alpha-thrombin preincubation. Exogenous 13-HODE (10 microM) reduced the augmented platelet adherence produced by coincubation of alpha-thrombin with platelets and endothelial monolayers, and eliminated the enhancement of platelet adherence produced by preincubation of alpha-thrombin with endothelial monolayers. 13-HODE also reduced the alpha-thrombin induced adherence of platelets to monolayers pretreated with aspirin and to fixed monolayers indicating a direct effect of 13 HODE as opposed to secondary effects mediated by the release of prostacyclin (PGI2) or endothelial derived relaxing factor (EDRF). Platelet adherence to subendothelial matrix was also reduced by 13-HODE. 13-HODE inhibited platelet aggregation initiated by 0.2 U/ml alpha-thrombin but did not affect aggregation initiated by 2.0 U/ml alpha-thrombin. These data provide evidence for the ability of exogenous 13-HODE to attenuate the interaction of thrombin activated platelets with endothelial cells as well as with other platelets. PMID- 1866715 TI - Phospholipase C mediated inhibition of factor VII requires triglyceride-rich lipoproteins. AB - The reduction of plasma factor VII (FVII) activity by phospholipase C (PLC), in vitro, has been proposed as a possible indication of a risk of cardiovascular disease. The ability of PLC to reduce FVII activity was found to require calcium ions and the presence of triglyceride-rich lipoproteins (e.g. chylomicra and very low density lipoproteins) rather than high or low density lipoproteins. The PLC mediated reduction of FVII activity was prevented by pre-incubation of PLC with chylomicra, before adding FVII, and this suggests that PLC may act on triglyceride-rich lipoproteins already bound to FVII in order to reduce FVII activity. At optimal PLC concentration, the extent of the reduction in FVII activity was proportional to the concentration of chylomicra. The detergent, Tween, prevented any loss of FVII activity, in both plasma and purified systems, if it was present at the beginning of the incubation with PLC. Addition of Tween, but not EDTA, after inhibition of FVII activity had occurred, caused a partial restoration of FVII activity. It is concluded that PLC reduces FVII activity by modifying triglyceride-rich lipoproteins to a form which binds to FVII, independently of calcium ions, and which inhibits procoagulant activity. The detection of PLC-sensitive procoagulant activity. The detection of PLC-sensitive FVII activity may therefore have no greater significance than the measurement of plasma triglyceride levels in predicting a risk of cardiovascular disease. PMID- 1866714 TI - Influence of thrombolytic agents on human platelet function. AB - In this study, we have evaluated the effects of four different thrombolytic agents, including Streptokinase from Hoechst and from Kabivitrum, Urokinase from Abbott and tissue plasminogen activator (t-PA) from Genetech, on platelet-rich plasma clots and platelet aggregation. At concentrations lower than 50 ugs/ml, t PA had no inhibitory effect on clot retraction or platelet aggregation induced by weak or potent agonist. At a higher concentration (greater than 100 ugs/ml), t-PA specifically antagonized the action of thrombin on clot formation and platelet aggregation. Streptokinase (Kabivitrum) potentiated the action of weak agonists on platelet aggregation, but the same agent from Hoechst had no negative or positive influence. None of the drugs tested had an adverse effect on platelet function at suggested therapeutic levels. None of the thrombolytic agents were capable of dissociating preformed clots made from platelet-rich plasma. However, all of them caused lysis of whole blood clots. Also, prior incubation of plasma alone or platelet-rich plasma with any of the agents prevented subsequent clot formation. The studies demonstrate that thrombolytic drugs at therapeutic concentrations do not affect platelet function adversely. They have a potent effect on whole blood clots, but not on clots from platelet-rich plasma. Therefore, platelets may play a critical role in determining the degree of reperfusion and the frequency of reocclusion following treatment with thrombolytic agents in vivo. PMID- 1866716 TI - Reference values of hemostasis related factors of healthy Japanese adults. II. Protein C. PMID- 1866717 TI - Antithrombotic activity of an unsaturated fatty acid preparation--comments. PMID- 1866718 TI - [What will the social service do with twice the current number of physicians?]. PMID- 1866719 TI - [Surgery--a domain to be reshaped]. PMID- 1866720 TI - [Nursing homes or homes for patients with senile dementia]. PMID- 1866721 TI - [Permanent admissions to nursing homes. Admission pattern changes between 1979 1989]. AB - Patients admitted permanently to a somatic nursing home between 1979 and 1989 were retrospectively studied to find out the mode of, and reasons for, admission. A total of 589 patients were admitted. The percentage of demented patients increased from 38 to 66%. The proportion of patients admitted from their own homes or from a hospital decreased, whereas the proportion transferred from a short admission to a permanent stay increased. It is concluded that, in many cases, the public services for elderly people living in their own homes are unable to cope with the problems that arise, especially in demented persons. The problem of "bed blockers" is no longer restricted to hospitals, but also affects nursing home beds allocated for short time purposes. It is necessary to develop a holistic approach to the tasks of caring for the elderly population, across existing administrative levels. PMID- 1866722 TI - [Endoscopic bile duct drainage--technique]. AB - The authors describe the technique of endoscopic implantation of endoprosthesis in the bile duct. From 1978 to 1989 implantation of endoprosthesis was successful in 88.7% of 212 patients. One to three procedures per patient were required for primary implantation. 407 procedures were performed; primary implantation, replacement of endoprosthesis and implantation of additional endoprosthesis. The success rate increased from 55% in the first third of the period to 82.4% in the last third. Ten patients had been previously operated with Billroth II gastrectomy and one with Whipple's operation. Implantation was successful in seven of these patients. PMID- 1866723 TI - [Endoscopic bile duct drainage--results]. AB - 212 patients were treated with endoscopic endoprosthetic drainage for bile duct obstruction. 137 patients had inoperable malignant obstruction, ten operable malignant tumor, 35 bile duct stones and 30 various benign strictures. Endoprosthetic stenting was successful in 188 patients (88.7%). The remaining 24 patients were treated with percutaneous transhepatic drainage or biliaryintestinal anastomosis, or received no treatment. In patients with successful implantation of endoprostheses, jaundice was relieved in 81% of the cases and pain in 89.6%. Cholangitis was treated with good results in 93.5%. Biliocutanous fistulas closed in two patients. Patency of the endoprostheses was 87 days on average. Replacement of endoprostheses or insertion of additional endoprostheses was performed 130 times. Complications occurred in 52 of 407 procedures (12.6%). Mortality related to the endoscopic endoprosthetic treatment was 4.2%. PMID- 1866724 TI - [Patellofemoral pain. Diagnosis and treatment]. AB - Patellofemoral pain is a frequent complaint among recreational and competitive athletes. Studies from Sweden and Norway among junior and senior high school students showed that every third to fourth student currently suffers, or has previously suffered, from patellofemoral pain. This paper presents current trends in diagnosis and treatment of patellofemoral pain. It describes the clinical examination, and discusses the additional information obtained from tests like radiography, CT and MT. Arthroscopy can establish the degree of cartilage damage and joint articulation, but should not be used as a general diagnostic tool. Treatment of patellofemoral pain should consist of patient education and a carefully designed rehabilitation programme emphasizing eccentric quadriceps exercises, primarily in close chain modes. A knee sleeve with a lateral cushion seems to alleviate symptoms in some patients. If the problems are not reduced by a well executed exercise programme over six months, surgical intervention should be discussed on the basis of a specific diagnosis. The article includes a review of recent studies on patellar shaving, spongialization, lateral release, proximal/distal realignment, tibial tubercle elevation and medialization, and patellectomy. PMID- 1866725 TI - [THARIES (Total Hip Articular Replacement by Internal Eccentric Shells) double cup prosthesis. A 10-year follow-up study]. AB - The concept of surface replacement or cup arthroplasty has been studied clinically for two decades, but few long-term studies have been published as yet. At the county hospital of Bodo the THARIES (Total Hip Articular Replacement by Internal Eccentric Shells) system was employed as a routine from 1979-86. 109 consecutively operated hips were followed up by clinical examination and radiological studies after three months, and after one, five and ten years. A loosening frequency of 21% was found after five years and 68% after ten years. At other centres the technique has been reserved mainly for younger patients with potentially solid bone stock. In this study we found 85% failures in the group of patients younger than 60 years at the time of arthroplasty, and 84% in males after ten years of observation. The results indicate that this conserving system is not strong enough to resume bearing weight, and does not have adequate resistance to fatigue to withstand years of cyclic loading, especially with a high level of activity. PMID- 1866726 TI - [Crohn disease found incidentally during cholecystectomy. Report of 3 cases with pronounced biliary tract problems]. AB - Gallstones are usually present in patients with Crohn's disease involving the distal ileum. This may be due to disturbances of the enterohepatic circulation, with bile salt malabsorption and secondary precipitation of cholesterol in the gallbladder. The article describes three patients who were cholecystectomized for cholelithiasis, and where Crohn's disease was found incidentally during laparotomy. PMID- 1866727 TI - [Study and treatment of urinary incontinence in women. A case load based study by general practitioners and gynecologists]. AB - 139 general practitioners and 190 gynaecologists responded to a case-history questionnaire about female urinary incontinence. More gynaecologists than general practitioners reported more frequent use of leakage provocation test, neurological examination, frequency-volume chart, and measurement of residual urine. Among the less relevant procedures, use of blood tests was reported more frequently by general practitioners, and use of x-rays and ultrasonography by gynaecologists. General practitioners preferred urine microscopy to urine culture. The opposite was true for the gynaecologists. 50% of the gynaecologists would prescribe oestrogens for the postmenopausal women, as against 25% of the general practitioners. Young women were instructed in pelvic floor exercises, incontinence pads were prescribed for elderly women. PMID- 1866729 TI - [Primary health care in developing countries]. AB - The Alma-Ata declaration and global strategy of Health for All by the year 2000 have given political and practical momentum to the delivery of primary health care in developing countries. WHO has provided leadership for this process, with support from other UN agencies and international donor organizations. Primary health care is based on the concept of a District Health System which provides comprehensive services. Community participation and intersectoral collaboration are the cornerstones of primary health care. Using Malawi, Uganda, India and Indonesia as examples, the article explores experiences of health problems and of health care delivery to underprivileged populations in African and Asian countries. PMID- 1866728 TI - [Drugs in developing countries. Current status, problems and possible solutions]. AB - Based mainly on economic, administrative and drug logistics indicators, the article critically reviews the use of drugs in less developed countries in the context of the global drug scene. The lack of balance in less developed countries (LDCs) between indicators of need and determinants of political, economic, professional, educational and sociocultural nature, including product marketing efforts is highlighted. Special emphasis is given to the global WHO Action Programme on Essential Drugs, its background, strategies, implementation and tentative impacts. Country case examples from Sri Lanka, Bangladesh, Kenya, Zimbabwe and the Gambia are used for illustration. Varying progress is made in about half the 110 LDCs which have formally adopted the WHO concepts. Delayed implementation, setbacks and failures are prevalent. These reflect financial and other resource constraints, political ambiguity, qualitative and quantitative deficiencies related to manpower and insufficient back-up measures of an educational and informative character. An orientation towards operational research based on competence-building according to needs and strategies is highly desirable. Accordingly a plea is made for multidisciplinary collaboration in North-South networks at university level. PMID- 1866730 TI - [Medical anthropology]. AB - This article presents medical anthropology as an inter-disciplinary and multi disciplinary field, in which anthropologists and biomedically trained professionals may find fruitful cooperation. Some aspects of international health care are discussed with special reference to anthropological contributions in this area. The author also touches on various problems encountered during the meeting between Norwegian clinicians and immigrant patients. PMID- 1866731 TI - [Abbot Vision. An interesting laboratory instrument for small hospitals]. AB - Abbott Vision is a technologically advanced chemistry analyzer developed for decentralized testing. About 30 different tests can be performed using disposable test packs containing wet reagents. The instrument was evaluated in a smaller hospital and (except for potassium) good results were obtained with respect to precision and conformity with results from a referral laboratory. The analyzer is considered to be of special advantage in cases of emergency and when there is no laboratory technician on duty. The cost per analysis is much higher, however, than with conventional techniques. PMID- 1866732 TI - [Infusor--an aid in cytostatic therapy]. AB - Infusor is a pump controlled by an elastomeric balloon. It has been used for continuous infusion of morphine, heparin, antiemetics and different kinds of cytostatics. The article presents our experience of Infusor when used for intravenous infusion of fluorouracil to patients with head and neck cancer. Infusor had many practical advantages. It provides a new possibility for continuous administration of cytostatics at home. A disadvantage was a slightly unstable infusion velocity. PMID- 1866733 TI - [Treatment of insulin-dependent diabetes]. PMID- 1866735 TI - [Administration procedures in the treatment with cytostatics]. PMID- 1866734 TI - [Reflux esophagitis--a therapeutic problem]. PMID- 1866736 TI - [The physician's role in dealing with patients unemployed for a long time]. AB - When medical practitioners examine unemployed persons, important considerations are medical and social diagnoses, risk factors and a possible need for counselling. Certification of illness and applications for rehabilitation or a disability pension are ambiguous and difficult tasks in the Norwegian health insurance system. Important measures are better unemployment benefits, more activation of unemployed persons, better educational opportunities, more information on health and unemployment, and a special health maintenance programme for long-term unemployed. PMID- 1866737 TI - [A health survey of persons unemployed for a long time in Greenland]. AB - In 1988 a random sample of 310 unemployed aged 16 to 63 years who had been registered for more than 12 weeks and lived in the four municipalities of Greenland was examined by a doctor and a nurse. Self-reported health and psychometric tests produced higher prevalences of disease than in a reference population of employed persons. On the basis of both clinical examination and the testing, 22% of the unemployed, were judged to be depressed, as against 2% in the reference group. 17% of the unemployed were scored as "morbidly anxious" and 17% as psychosomatically sick, as against 2% and 4% of the references. The health and social services which the group had received were regarded as unsatisfactory, both by the doctor and by the unemployed themselves. A special health maintenance programme is proposed for long-term unemployed. PMID- 1866738 TI - [The role of a drug and therapeutics committee in primary health care. Experiences from the 16/Furuset District, Oslo]. AB - In 1984 a Committee on Drugs was established in the primary health care district of Furuset. The committee members represented pharmacists at the local pharmacy, nurses and general practitioners in this sector. The committee has arranged 1-3 meetings yearly for all primary health care personnel at Furuset. A well-prepared topic was discussed at each meeting. Additional joint meetings have taken place regularly between physicians, pharmacists and representatives of the pharmaceutical industry. Simple equipment has been developed for communication between general practitioners and the pharmacy. Inquiries have been carried out on prescription practices and drug use. PMID- 1866739 TI - [Mammography--remember the false negative]. PMID- 1866740 TI - [High and low use of social and health services]. PMID- 1866741 TI - [Quality assurance of medical technical equipment]. PMID- 1866742 TI - [Perinatal HIV infection]. PMID- 1866743 TI - [An epidemic among yachtmen]. PMID- 1866744 TI - [On reproducibility and per cents]. PMID- 1866746 TI - Microinfarction in classic migraine? A study with magnetic resonance imaging findings. AB - By means of magnetic resonance imaging we investigated a total of 45 patients suffering from classic migraine; 25 patients had been treated in our department for classic migraine over the past 2 years (group A), and 20 other patients investigated between 1976 and 1984 were reexamined for this study (group B). Thirty-two age- and roughly sex-matched healthy volunteers underwent magnetic resonance imaging and served as controls (group C). There was a trend for patients with classic migraine to have more subcortical patchy lesions on T2 weighted magnetic resonance imaging. In a comparison of our control subjects and patients with a history of greater than 20 attacks of classic migraine taken from groups A and B, this difference in number of lesions was significant (p = 0.02). The results suggest that patchy lesions in patients with classic migraine should be interpreted with particular caution before diagnosing a demyelinating disease since the lesions could be ischemic in origin. PMID- 1866745 TI - Immunohematologic characteristics of infection-associated cerebral infarction. AB - We evaluated 50 consecutive patients with acute ischemic stroke to assess the prevalence of systemic infection preceding the neurological event. We analyzed the immunohematologic characteristics of patients with and without signs and/or symptoms of a preceding infectious process. Patients were examined less than or equal to 7 days after cerebral infarction and evaluated for fibrinogen, anticardiolipin antibodies, fibrin D-dimer (a fragment of cross-linked fibrin), plasminogen activator inhibitor-1, and protein S. Of the 50 patients, 17 had symptoms of infection beginning less than or equal to 1 month before the stroke (11 had upper respiratory tract infections, three urinary tract infections, two subacute bacterial endocarditis, and one pneumonia). Compared with patients without infection, patients with infection had significant increases in fibrin D dimer concentration (5.3 +/- 1.1 versus 4.7 +/- 0.9 log-transformed ng/ml, p less than 0.05) and cardiolipin immunoreactivity, IgG isotype (1.8 +/- 1.3 versus 1.1 +/- 0.9 log-transformed phospholipid units, p less than 0.04), and, when studied less than or equal to 2 days after the stroke, increased fibrinogen levels (459 +/- 126 versus 360 +/- 94 mg/dl, p less than 0.05). In conclusion, infection associated cerebral infarction is common and is associated with substantial immunohematologic abnormalities. PMID- 1866747 TI - Remote cortical dysfunction in aphasic stroke patients. AB - We studied the effect of deep-seated left hemispheric lesions on cortical blood flow in 18 right-handed aphasic stroke patients. Regional cerebral blood flow was measured at rest and during the performance of a functional naming test using the two-dimensional xenon-133 inhalation method. Compared with 10 controls, at rest the patients showed regional cortical hypoperfusion in the left frontoparietal region. In the controls, activation patterns from the rest to the test condition involved mainly the left hemisphere areas. In the patients, a lack of blood flow change was observed in several areas that were usually hypoperfused at rest. However, in patients with slight verbal expression disorders there were obvious blood flow increases in other brain regions in both hemispheres. Such cortical functional reorganization and the presence of a remote cortical dysfunction could play a role in the pathophysiology of language disorders. PMID- 1866748 TI - Snoring and the risk of ischemic brain infarction. AB - To determine if a history of snoring is a risk factor for brain infarction, I conducted a case-control study of risk factors for ischemic stroke using 177 consecutive male patients aged 16-60 (mean 49) years with acute brain infarction. For each patient I chose an age-matched (+/- 6 years) male control. Arterial hypertension, coronary heart disease, snoring (habitually or often), and heavy drinking (greater than 300 g/wk) were risk factors in the stepwise multiple logistic regression analysis. The odds ratio of snoring for brain infarction was 2.13. By McNemar's test this association increased strongly if a history of sleep apnea, excessive daytime sleepiness, and obesity were all present with snoring (odds ratio 8.00). My study indicates that snoring may be a risk factor for ischemic stroke, possibly because of the higher prevalence of an obstructive sleep apnea syndrome among snorers than nonsnorers. PMID- 1866749 TI - Benefit of a stroke unit: a randomized controlled trial. AB - In a randomized controlled trial we compared the clinical outcome of acute stroke patients, 110 of whom were allocated to treatment in a stroke unit and 110 to treatment in general medical wards. No significant difference existed between these groups with regard to sex, age, marital status, medical history, or functional impairment on admission. Outcome was measured at 6 and 52 weeks after the stroke by the proportion of patients at home, the proportion of patients in an institution, the mortality, and the functional state. After 6 weeks 56.4% of the patients randomized to the stroke unit and 32.7% of the patients randomized to the general medical wards were at home (p = 0.0004), and after 52 weeks 62.7% and 44.6%, respectively, were at home (p = 0.002). After 6 weeks 36.3% of the patients from the stroke unit and 50.0% from the general medical wards were in an institution (p = 0.02); after 52 weeks 12.7% and 22.7%, respectively, were institutionalized (p = 0.016). After 6 weeks mortality was 7.3% for the stroke unit group and 17.3% for the general medical wards group (p = 0.027). After 52 weeks mortality was 24.6% for the stroke unit group and 32.7% for the general medical wards group (difference not significant). Functional state was significantly better for patients treated in the stroke unit after both 6 and 52 weeks. We conclude that care of patients with acute stroke in a stroke unit improves clinical outcome compared with treatment in general medical wards. PMID- 1866750 TI - Temporal thresholds for neocortical infarction in rats subjected to reversible focal cerebral ischemia. AB - We investigated the temporal threshold for focal cerebral infarction in the spontaneously hypertensive rat. The right middle cerebral artery and common carotid artery were occluded for 0, 1, 2, 3, 4, or 24 hours, and all the animals were sacrificed 24 hours after the onset of ischemia. Cortical infarct volumes and edema volumes were quantified in serial frozen sections of hematoxylin and eosin-stained tissue using image analysis. Upon occlusion, blood flow in the core of the ischemic zone, measured with laser-Doppler flowmetry, fell to a mean +/- standard deviation of 21 +/- 7% of the preocclusion baseline value (n = 26). During the first hour of ischemia, blood flow in the densely ischemic zone rose to 27 +/- 8% of baseline (n = 25). Release of the middle cerebral artery and common carotid artery occlusions rapidly restored cortical blood flow to 213 +/- 83% of baseline (n = 21). Focal ischemia of 1 hour's duration caused little or no infarction, while ischemic intervals of 2 and 3 hours produced successively larger volumes of infarcted cortex. Ischemic intervals of 3-4 hours' duration followed by approximately 20 hours of recirculation yielded infarct volumes that were not significantly different from those after 24 hours of permanent focal ischemia. The results indicate that 3-4 hours of focal cerebral ischemia in this rat model is sufficient to attain maximal infarction and suggest that recirculation or pharmacological interventions after this time will provide little benefit. PMID- 1866751 TI - Forebrain ischemia induces selective behavioral impairments associated with hippocampal injury in rats. AB - Two groups of rats were tested on a variety of motor and cognitive tasks after either 10 minutes of two-vessel occlusion forebrain ischemia (n = 8) or sham operative procedures (n = 6). Histological injury was absent in the sham-operated group. In the ischemic group, hippocampal injury was restricted to field CA1, while damage in the neocortex and caudoputamen was sparse. Motor tests performed on postoperative days 18 and 28 revealed no significant differences between the ischemic and sham-operated groups. Retention performance of a radial maze discrimination task was impaired, with a significant but transient increase in both working and reference memory errors. Passive avoidance acquisition and retention were not significantly affected, although conclusions concerning the utility of this task must be reserved because of variability in the behavior of the sham-operated rats. Morris maze spatial navigation (place learning) and open field activity were insensitive to treatment group. These functional results are consistent with the observed histological injury and what is known about hippocampal injury and behavior, and they provide further guidance for the development of neurological assays appropriate for discriminating outcome from forebrain ischemia in rats. PMID- 1866752 TI - LY178002 reduces rat brain damage after transient global forebrain ischemia. AB - Several feasible mechanisms have been proposed as sources of neuronal damage from ischemia and subsequent reperfusion. Included among these are oxidative damage caused by free radical production and lipid peroxidation and products derived from phospholipid breakdown. A series of 4-thiazolidinone compounds represented by LY178002 (5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene-4 thiazolidinon e) have been described as inhibitors of multiple enzymes in the arachidonic acid cascade, including fatty acid cyclooxygenase, 5-lipoxygenase, and phospholipase A2. Accordingly, we evaluated LY178002 in a four-vessel occlusion model of global forebrain ischemia with reperfusion. A 2-hour pretreatment of 11 male Wistar rats with 150 mg/kg LY178002 significantly protected against striatal (p = 0.0007) and hippocampal CA1 (p = 0.006) damage after 30 minutes of global ischemia. Similar protection was observed for the striatum (p = 0.005) and hippocampal CA1 layer (p = 0.025) after pretreatment of 13 rats with 50 mg/kg LY178002. We further evaluated LY178002 as a possible inhibitor of lipid peroxidation because part of its chemical structure incorporates the aromatic backbone of the known antioxidant butylated hydroxytoluene. We found LY178002 to be a potent inhibitor of iron-dependent lipid peroxidation. Few substances possessing a single pharmacological activity have been found to be of significant therapeutic benefit in global ischemia of 30 minutes' duration because the mechanisms that lead to cell death in response to ischemia are likely to be multifactorial. Thus, the efficacy of LY178002 in this model may be due to its ability to inhibit multiple sources of damage. PMID- 1866753 TI - Platelet emboli in rat brain cross when the contralateral carotid artery is occluded. AB - The pathogenesis of embolic events ipsilateral to an occluded carotid artery is uncertain. To examine this question we combined occlusion of the left common carotid artery with embolism from the right common carotid artery in rats. Following ligation of the left carotid artery in 20 experimental rats, we irradiated the right carotid artery with a laser (632 nm, 200 mW/cm2, 12-15 minutes) following the intravenous injection of 12.5 mg/kg of the photosensitizing agent Photofrin II. Controls had left carotid artery occlusion with (n = 13) or without (n = 6) Photofrin II. Fifteen of the 20 experimental rats survived to be perfused at 24 hours; cerebral infarcts were identified in 12 rats, with bilateral infarcts in 10. There were 112 infarcts (101 small [less than 2.5 mm] and 11 large [greater than 2.5 mm] on the right and 103 (93 small and 10 large) on the left. Emboli were seen in association with some infarcts and were evenly distributed in the two hemispheres (37 emboli on the right and 40 on the left, with the midline azygous artery occluded in four animals). Left carotid artery occlusion did not produce infarcts or emboli in the controls. We conclude that cerebral infarcts in the distribution of an occluded common carotid artery may be caused by emboli from the contralateral carotid artery in rats. PMID- 1866754 TI - Stroke from other etiologies masquerading as migraine-stroke. AB - There has been a recent increase in the number of studies dealing with migraine stroke. I describe five patients in whom migraine-stroke was the clinical diagnosis but in whom the subsequent clinical events or autopsy showed a different mechanism for the cerebral infarction. Three patients had arterial dissection (one proven at autopsy), one had marantic endocarditis that had been missed on two echocardiograms (proven at autopsy), and one had generalized atherosclerosis and diabetes. These patients demonstrate that important and different etiologies may produce what seems to be the migraine-stroke syndrome. The result may be failure to recognize specific therapeutic measures that could have vitally important benefit to the patient. PMID- 1866755 TI - Safety and tolerance of oral dextromethorphan in patients at risk for brain ischemia. AB - Experimental ischemia models have shown the antitussive dextromethorphan to be an N-methyl-D-aspartate antagonist with neuroprotective properties. We treated 10 patients with a history of recent stroke or transient ischemic attack with oral dextromethorphan (60 mg q.i.d.) for 3 weeks in a placebo-controlled, double blind, crossover tolerance study. We documented no clinical evidence of toxicity attributable to dextromethorphan in this preliminary study. PMID- 1866756 TI - Review of the variability of the territories of the major cerebral arteries. AB - The results of recent model studies indicate that the variability in territorial distribution of the major cerebral arteries may be much greater than has been previously recognized. We review the literature on the cortical and intracerebral territories of the anterior, middle, and posterior cerebral arteries. Although most authors claim that these territories are relatively consistent, the results of their studies show many and considerable discrepancies. The variability described by Beevor has been neither excluded nor completely confirmed, yet somehow the concept of a relatively unchanging pattern of the peripheral cerebral vascularization has gradually settled into the literature. We discuss the considerable variability of the cerebral territories, as well as the discrepancies in investigation techniques, injection materials, and specimen conditions that could be factors producing these dissimilar results. Our study shows that there are no arguments in the literature to negate the variability of the cerebral territories. PMID- 1866757 TI - Defining "progressive stroke". PMID- 1866758 TI - Stroke and atrial fibrillation. PMID- 1866759 TI - Procoagulant states and stroke. PMID- 1866760 TI - Stroke in relapsing thrombotic thrombocytopenic purpura. PMID- 1866761 TI - Correlation between plasma fibrinogen levels and white blood cell count after cerebral infarction. PMID- 1866762 TI - Sex difference in effect of aspirin on blood platelet aggregation may be artifact. PMID- 1866763 TI - Congenital antithrombin III abnormality and cerebral arterial thrombosis. PMID- 1866764 TI - A review of hemoglobin and the pathogenesis of cerebral vasospasm. AB - We believe that current experimental and clinical evidence can be most satisfactorily interpreted by assuming that oxyhemoglobin is the cause of cerebral vasospasm that follows subarachnoid hemorrhage. We review the pathogenetic mechanisms by which oxyhemoglobin affects cerebral arteries. The relative importance of each of these mechanisms in the genesis of vasospasm, the biochemical pathways of oxyhemoglobin-induced smooth muscle contraction, and the intracellular actions of oxyhemoglobin on smooth muscle and on other cells in arteries are still not definitely established. PMID- 1866765 TI - Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. AB - The impact of nonrheumatic atrial fibrillation, hypertension, coronary heart disease, and cardiac failure on stroke incidence was examined in 5,070 participants in the Framingham Study after 34 years of follow-up. Compared with subjects free of these conditions, the age-adjusted incidence of stroke was more than doubled in the presence of coronary heart disease (p less than 0.001) and more than trebled in the presence of hypertension (p less than 0.001). There was a more than fourfold excess of stroke in subjects with cardiac failure (p less than 0.001) and a near fivefold excess when atrial fibrillation was present (p less than 0.001). In persons with coronary heart disease or cardiac failure, atrial fibrillation doubled the stroke risk in men and trebled the risk in women. With increasing age the effects of hypertension, coronary heart disease, and cardiac failure on the risk of stroke became progressively weaker (p less than 0.05). Advancing age, however, did not reduce the significant impact of atrial fibrillation. For persons aged 80-89 years, atrial fibrillation was the sole cardiovascular condition to exert an independent effect on stroke incidence (p less than 0.001). The attributable risk of stroke for all cardiovascular contributors decreased with age except for atrial fibrillation, for which the attributable risk increased significantly (p less than 0.01), rising from 1.5% for those aged 50-59 years to 23.5% for those aged 80-89 years. While these findings highlight the impact of each cardiovascular condition on the risk of stroke, the data suggest that the elderly are particularly vulnerable to stroke when atrial fibrillation is present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866767 TI - An autopsy study of the incidence of lacunes in relation to age, hypertension, and arteriosclerosis. AB - We investigated selected features of lacunes in 1,086 necropsy cases. Lacunes were found in brains from patients above the age of 40 years and were most common in brains from persons in their sixties but decreased in number in brains from older persons. The most common site of lacunes was the frontal lobe white matter, followed by the putamen, pons, parietal lobe white matter, thalamus, and caudate nucleus in descending order of frequency. By dividing the 1,086 cases into three groups according to blood pressure, we found more lacunes in the hypertensive and borderline hypertensive groups than in the normotensive group; the average number of lacunes per brain in each group was 3.61, 2.77, and 1.15, respectively. Diastolic hypertension was more closely related to the number of lacunes than was systolic hypertension. The extent of arteriolosclerosis of the medullary arteries in the frontal lobe white matter was measured and compared with the number of lacunes. There was a close correlation between lacunes and arterioloslerosis in all age groups. PMID- 1866766 TI - Regression of carotid plaques during low density lipoprotein cholesterol elimination. AB - We performed serial prospective ultrasound examinations of four flat and 17 soft carotid plaques during an average of 17 months in seven patients with heterozygous hypercholesterolemia during heparin-induced extracorporeal low density lipoprotein elimination on precipitation from plasma. By means of a specially designed quantitative three-dimensional ultrasound analysis, significant plaque volume reduction could be evaluated in all subjects, along with a marked reduction of total and low density lipoprotein cholesterol and fibrinogen serum levels. PMID- 1866768 TI - Risk factors for stroke as predictors of platelet membrane fluidity in Alzheimer's disease. AB - We have previously reported that increased platelet membrane fluidity identifies a subgroup of patients with Alzheimer's disease who have distinct clinical features including an earlier age of symptomatic onset, a more rapidly progressive cognitive decline, and a decreased prevalence of focal electroencephalographic findings. In the current study, these patients also exhibited a decreased prevalence of risk factors for stroke compared with patients who had normal platelet membrane fluidity. Our findings suggest that the platelet membrane abnormality describes a clinical subgroup of patients with Alzheimer's disease who are less likely to have coexisting cerebrovascular disease than the remaining patients who meet clinical consensus criteria for probable Alzheimer's disease. PMID- 1866769 TI - Differentiation and maturation of macrophages into interdigitating cells and their multicellular complex formation in the fetal and postnatal rat thymus. AB - Three mouse anti-rat macrophage monoclonal antibodies, TRPM-1, TRPM-2, and TRPM 3, as well as anti-rat Ia monoclonal antibody, were used to study the emergence, differentiation, and maturation of macrophages in the fetal and postnatal rat thymus immunohistochemically and immunoelectron microscopically. At 14 days of gestation, primitive/fetal macrophages entered the thymic primordium and showed Ia expression, where afterwards the epithelial cells also expressed Ia antigens prominently at 15 days of gestation. After 16 days of gestation, differentiation of a subpopulation of primitive/fetal macrophages into interdigitating cells (IDCs) is suggested. From 19 days of gestation, TRPM-1-positive dendritic cells including IDCs started forming multicellular complexes with thymocytes and the epithelial cells also formed similar complexes with thymocytes. One day after birth, TRPM-1 positive IDC-thymocyte complexes distributed throughout the thymic medulla. The number of TRPM-1- and Ia-positive IDCs increased by day, and Langerhans cells (LCs) appeared in the thymic medulla within a few days after birth. By two weeks after birth, the distribution pattern of Ia- and TRPM-1 positive cells became similar to that of adult rats. In ontogeny, intimate cell membrane appositions were frequently observed between thymocytes and Ia-positive epithelial cells or IDCs in the thymic multicellular complexes. These complexes were discriminated into two types; epithelial cell-thymocyte complexes and IDC- or LC-thymocyte ones. In vitro, two types of the thymic nurse cells (TNCs) were identified: epithelial cells and IDCs or LCs. Besides epithelial cells, IDCs or macrophages formed rosettes with thymocytes. These TNCs and rosettes in vitro seem to correspond to the thymic multicellular complexes in vivo. PMID- 1866770 TI - In vitro thymopentin modulation of mitogen responsive T-cell precursor frequency. PMID- 1866771 TI - Effect of hydrocortisone on the axial organ of the sea star Asterias rubens. AB - Sea stars Asterias rubens were inoculated daily with hydrocortisone. After 3 days a plaque of lysis was formed in the center of the axial organ and increased in size if the injections were continued for 2 more days. This result is reminiscent of the effect of cortisone on the thymus of vertebrates and supports the hypothesis that the axial organ is an ancestral lymphoid tissue. PMID- 1866772 TI - [Mental health care and independence of the elderly--notes by a psychiatrist]. PMID- 1866773 TI - [Problems of the elderly and themes in science]. PMID- 1866774 TI - [A differentiated approach to aging--contribution to a discussion]. PMID- 1866775 TI - [Future scenario's Dementia 1990-2010--various major points from the scenario report 'Care for mental health in the future']. AB - This paper describes major points of a study on the future of dementia in the period 1990-2010. By means of a literature review and consultation of experts in a Delphi-study exploratory scenarios and a target-setting scenario were constructed. The paper delineates the exploratory reference-scenario, which includes the most probable processes and developments according to the majority of the experts. Furthermore necessary measures and strategies are described to increase the quality of care to demented elderly in the next twenty years. PMID- 1866776 TI - [The gerontological 21st century or the 21st-century gerontology]. PMID- 1866777 TI - [The elderly from the viewpoint of the family practitioner]. PMID- 1866778 TI - [A meta-theoretical and meta-disciplinary viewpoint?--On geriatrics and gerontology in the next century]. PMID- 1866779 TI - [Potential developments in gerontology and geriatrics from a cognitive point of view]. PMID- 1866780 TI - [Do the rules of the game for research remain the same? Yes!]. PMID- 1866781 TI - [Quality of research and interaction between disciplines. Contribution to a discussion]. PMID- 1866782 TI - [Determination of sex in 7-day bovine embryos after microsurgical division]. AB - A possibility of the cytogenetic sexing of 7-day microsurgically bisected bovine embryos by one of 2-4 parts with the aim of their selection by sex and peculiarities of the karyotype before their transplantation has been studied. Metaphase plates of chromosomes from halves and quarters of late morulae and early blastocysts for the cytogenetic analysis have been obtained. PMID- 1866783 TI - [Lengths of the rearranged chromosome fragments and reproductive-compensatory ability in families with carriers of reciprocal translocations with habitually unfavorable pregnancy outcomes]. PMID- 1866784 TI - [Features of the femur periosteum and endosteum structure in rodents and hares]. AB - General and some special histologic methods have been used to study the structure of periosteum and endosteum, as well as the morphological peculiarities of their cells in rodents and hares in the early and late postnatal ontogenesis. It is established that the periosteum of animals under study is represented by a two layer structure: the outer (protective) layer and the inner (osteogenic) one. The outer layer consists of fibroblast-like cells, the inner one of osteogenic cells (pre-osteoblasts and osteoblasts). Endosteum is represented only by osteogenic cells and, unlike the periosteum, possesses no independent fibrillar structure; therefore, it appears to be more labile than the periosteum. PMID- 1866785 TI - [Analysis of morphometric indices in mice for registration of induced mutations in germ cells]. AB - The new-born mice of the first generation have been examined for changes in morphometric indices after the influence of fopurine, cyclophosphamide and cadmium chloride on their fathers. It is shown that fopurine and cyclophosphamide, the mutagens for mammals, increase the variability of morphometric indices. The method to calculate the morphometric indices of mice may be used for evaluating genetic risk of the compounds for man. PMID- 1866786 TI - [Effect of mutant genes db(diabetes) and m(misty) on the severity of high-dose streptozotocin diabetes in C57bl/KsJY mice]. AB - It is stated that high-dose streptozotocin diabetes is more serious in gene db homozygous mice of mutant line C57BL/KsJY than in heterozygotes db +/+ m and mice M+/+m. Manifestation of spontaneous insulin-independent diabetes mellitus in homozygotes db decreases the level of hyperglycemic streptozotocin-induced reactions. PMID- 1866787 TI - [C-polymorphism of chromosomes in men with azoospermia]. AB - Comparative evaluation of absolute C-segment lengths of chromosomes 1, 9, 16 and Y in 50 azoospermic males has revealed significant differences in chromosome 9 between 50 normal males. These results are considered as nonrandom in pathology of male gametogenesis. PMID- 1866788 TI - [Characteristics of digital and palmar dermatoglyphics in people of different ages living in the territory of the Ukrainian Polesie]. AB - Examination of dermatoglyphs in people aged 50-103 living in the territory of the Ukrainian Polesie has revealed age differences in some indices of dermatoglyphics: total crest count, palmar angle, character of the cutaneous pattern of fingers. It assumed that these differences have arisen as a consequence of selection of persons characterized by high reliability of the genotype functioning. The data obtained permit supposing that it is possible to use dermatoglyphics for determining hereditary predisposition of people to longevity. PMID- 1866789 TI - [The clinal variability of the B-chromosome system in the East Asian mouse Apodemus peninsulae from Buryatia and Mongolia]. AB - Karyological investigation of 22 East-Asiatic mice from different points of the North Mongolia showed the availability in all the mice from 1 to 13 B chromosomes, including from 1 to 5 middle-sized and small two-shoulder chromosomes, from 0 to 11 dot-like B chromosomes, and, seldom, 1 small acrocentric B chromosome. Nearly every mouse is characterized by its variant of B chromosome system. Most frequent mice with 3, 4 and 8 B chromosomes were met. The comparison of the B-chromosome system variants in mice from Buryatia, Chita Province (USSR) and the North Mongolia, showed an increase in the number of B chromosomes, mainly at the expense of the number of dot-like B chromosomes, in the direction from Ulan-Ude to the south and to the east. PMID- 1866790 TI - [The dynamics of postmortem cellular changes. Ultrastructural-histochemical research]. AB - Lactate dehydrogenase (LDG), glucose-6-phosphate dehydrogenase (G-6-PDG), isocitrate dehydrogenase (ICDG) as well as acid phosphatase (AcPase) activities were assessed in the rat tracheal ciliated epithelial cells using cytophotometry, combined with ultrastructural AcPase demonstration within 1 to 5 hours after animal death. A moderate gradual reduction of LDG, G-6-PDG and AcPase, but not ICDG activities has been detected in the groups of initially unaffected and hypertensive rats. The activities of all dehydrogenases progressively decreased compared to the stable AcPase values in rats which died from acute renal failure. AcPase reaction products were found to be released from the Golgi apparatus and lysosomes into the adjacent cytoplasm and across the plasma membrane. Occasionally AcPase activity emerged in the cis- and intermediate lamellae of the Golgi apparatus. The perturbations in the membrane permeability evidenced by AcPase leakage can be considered as the most likely mechanism for the observed postmortem reduction of some enzymatic activities tested. PMID- 1866791 TI - [Electron microscopic research on cryptosporidia. III. Parasite-host relations]. AB - A study was made of the host-parasite relationship with Cryptosporidium parvum (Apicomplexa, Sporozoa), which parasitizes the intestine of newborn rats experimentally infected with oocysts isolated from C. parvum-infected calves. The endogenous development of the parasite occurs extracytoplasmically in the microvillar compartment of the enterocytes. The formation of the extracytoplasmic parasitophorous vacuole (PV), like that surrounding the endogenous stages of C. parvum, is regarded as one of the possible and evolutionary established ways for the intracellular parasite to escape from the host cell lysosomal digestion. Special attention is paid to the attachment zone of C. parvum, where a multimembranous organelle is formed serving eventually as a feeder organelle. No other specialized cytostome, similar to the micropore of other coccidia, has been so far revealed in the growing stages of Cryptosporidium. The characteristic ultrastructural organization of the endogenous stages of C. parvum and of other Cryptosporidium species so far investigated, along with the peculiar structure of the cryptosporidia-surrounding PV, to say nothing of some other distinctive features--all this makes it possible to distinguish between the genus Cryptosporidium and other coccidian genera, and warrants the separation of the former into a separate family Cryptosporidiidae Leger, 1911. Unlike, the addition to this family, besides Cryptosporidium Tyzzer, 1910, of another genus, Epieimeria Dykova, 1981, on the ground of the "epicellular" localization of both the genera claimed by Levine (1984), seems hardly correct, due to the totally different patterns of ultrastructural organization and host-parasite relationship recently reported for Epieimeria anguillae by Molnar and Baska (1986). PMID- 1866792 TI - [The structural organization of the cytoskeleton of the mammary secretory cells]. AB - A study was made of the arrangement and specialties of distribution in the mammary secretory cells of albino mice of the following cytoskeleton ultrastructures: microtubules (MT), organization centres (MTOC), microfilaments (MF) and intermediate filaments (IF). During the last period of pregnancy and at different stages of lactation, for the alveolar epithelium the presence of a single material centrioles (CN) was shown in the region of the apical surface near dense intercellular contact. During pregnancy and especially at the beginning of lactation (1-2 days) the relatively large density of the MT was observed in both the cytoplasm of the secretory cells and the region near the CN. On the most hard days of lactation (10 day) the lowering of the number of all the observed structures was held in the majority of the cells. The MT was not observed near the CN. It appeared that the elimination of the MTOC activity during the most hard time of lactation is related to the decrease in the numbers of MT, MF and IF. The pattern of cytoskeleton reorganization, associated with the development of the functional activity of the observed cells, enables us to suggest a cooperative contribution of its base components in the formation of the secretory surface and in the carrying out of exocytosis. PMID- 1866793 TI - [Cytoplasmic RNA in neocortical neurons in vitro]. AB - The investigation of the ratio of neuronal cytoplasmic RNA mono- and two-chain sections was performed in thin neocortical slices by means of fluorescent probing. Changes of the relative intensity of Acridine Orange red luminescence indicated a decrease in the quota of monochain sections in the common neuronal RNA pool. In eight hours of superfusion it was authentically less than in the control slices and in the slices which were incubated during four hours. Deep profiles of red fluorescence became plane in the process of incubation. It was suggested that the essential decrease in the red luminescence intensity of cytoplasmic RNA in vitro, observed between four and eight hours, may be conditioned by disintegration of polysomes to monosomes, and this, in its turn, may cause the decrease in ribosomal synthetic activity. PMID- 1866794 TI - [The inhibition of mitosis in tissue culture cells by blue light]. AB - Blue light (wavelength 350-480 nm) irradiation of the early mitotic (prophase and prometaphase) tissue culture cells at the dose of 50-3000 J/cm2 delay mitosis or completely block it at the metaphase. Cell sensitivity to the near UV light (wavelength 360 nm) was few times more as compared with the sensitivity to the visible light (wavelength 400-480 nm). Mitotic cells irradiated with the green light (wavelength more than 500 nm; dose up to 7500 J/cm2) completed division normally. The effect of the blue light did not depend on the presence of phenol red in tissue culture medium. Rhodamin 123 staining did not show any changes in the mitochondrial system in the irradiated mitotic cells. Blue light irradiation with the dose enough for the induction of mitotic delay appears to be insufficient to affect the proliferation of interphase cells. PMID- 1866795 TI - [The relationship of the saturation density of multilayer cell cultures to their mass exchange with the medium]. AB - Chinese hamster fibroblasts (CHF) and NIH 3T3 cells were cultured on a glass substrate at different distances from the porous membrane separating the cells from the perfusing medium. It is shown that with perfusion of medium above the membrane there is no movement of the medium near the cells. In both the types of culture, the cells grow in multilayers, however the multilayer character of growth in CHF is more pronounced than in NIH 3T3 cells. The saturation density of the cultures depends on the cell-membrane separation, and at separations of no more than 0.2 mm exceeds the saturation density in the monolayer by 8-10 fold. The dependences of the saturation density on separation are different for CHE and NIH 3T3 cells, indicating qualitative differences in the inhibition of cell growth in monolayers between these cultures. The results obtained indicate that the inhibition of cell growth in monolayer is due to mass exchange limitations, rather than to intercellular contact interactions. PMID- 1866796 TI - [The proliferative characteristics of cells in culture during perfusion of the medium]. AB - The proliferation of Chinese hamster fibroblasts (CHF) and NIH 3T3 cells was studied at different flow rates immediately above the cells. It is shown that there is a limiting density of saturation of the perfused culture that accounts for 1.7 x 10(6) - 2.0 x 10(6) cells/cm2 for NIH 3T3 cells, and for 6 x 10(6) - 7 x 10(6) cells/cm2 for CHF. The growth curves and the distribution of cells with respect to the phases of the cell cycle during cultivation with and without perfusion are presented. Based on the results obtained it is assumed that the limit of saturation density of perfused CHF culture is due to the mass transfer of the growth-inhibiting metabolites inside the multilayer structures. The assumption seems to hold true for NIH 3T3 cells, too, even though the multilayer character of growth of this culture is less pronounced than in CHF. PMID- 1866797 TI - [The ultrastructure of the hepatocyte contacts in inbred mice at different ages]. AB - Correlation was revealed between the ultrastructure of hepatocyte contacts and force F, essential for the rupture of the junction between the cell, seized with a microneedle, and the tissue specimen, in mice of the highly cancerous CBA line and of the low cancerous C57BL line at the age of 1.7 and 15 months. The most considerable ultrastructural differences in the cell contacts were found in the above mice at the age of 1 month, when the signs of carcinogenic process cannot yet been seen. It is shown that the differences in force F of these mice are not associated with the structural changes in hepatocyte contacts which may be due to the differences in durability properties of the cytoskeleton. PMID- 1866798 TI - [A method for determining double-stranded DNA breaks in eukaryotic cells]. PMID- 1866799 TI - [Hydatid cyst of the lung. Reflections on the importance of scanning in 47 diagnostic errors]. PMID- 1866800 TI - [Outcome of aortic valve diseases neglected during mitral surgery]. PMID- 1866801 TI - [Zinc]. PMID- 1866802 TI - [Myocardial infarction without Q wave. Clinical course characteristics and therapy]. PMID- 1866803 TI - [Urinary infection at a urology service]. PMID- 1866804 TI - [Occupational handicap and psychiatry]. PMID- 1866805 TI - [The conditioned reflex of Pavlov or the conditioned reflex of El Jahiz]. PMID- 1866806 TI - [Hydatid cyst in the thyroid in children. 3 cases]. PMID- 1866807 TI - [Pituitary apoplexy. 3 cases]. PMID- 1866808 TI - [Methemoglobinemia in infants. An acquired toxic form and a congenital recessive form]. PMID- 1866809 TI - [Diagnosis and treatment of patients with minor head injuries]. PMID- 1866810 TI - [Nosocomial virus infections in pediatric departments. Rotavirus and respiratory syncytial virus]. AB - Rotavirus and Respiratory Syncytial virus are common causes of acute gastroenteritis and upper and lower respiratory diseases among infants and toddlers. Both viruses occur as epidemics during the winter season. The symptoms may be quite severe and often lead to hospitalisation in paediatric wards i.e. about 2,000 children per year. The viruses frequently give rise to nosocomial infections in the infant/toddler wards about one third of the cases being nosocomial. Recent studies have revealed that both viruses are spread via contaminated hands. The density of virus in faeces and upper respiratory secretions is very high less than one microgram being sufficient for spread of the disease. The traditional precautions (i.e. handwashing and isolation) have failed to reduce the numbers of nosocomial infections to an acceptable level. However, the routine use of gloves have been shown to reduce the spread of RS virus effectively. This method is suggested in paediatric wards during the winter since it presumably will also reduce the spread of Rotavirus. PMID- 1866811 TI - [Atrial fibrillation--thromboembolism and prevention]. AB - Chronic non-rheumatic atrial fibrillation is associated with a risk of thromboembolic complications of about 5% per year. Previous myocardial infarction seems to be a significant risk factor for development of thromboembolic complications in chronic atrial fibrillation, whereas paroxysmal atrial fibrillation and isolated atrial fibrillation in younger patients may be associated with a lower risk of emboli. Silent cerebral infarction occurs more often in chronic atrial fibrillation than among controls in sinus rhythm. Three prospective trials of patients with atrial fibrillation found effect of warfarin on the occurrence of thromboembolic complications. In one study aspirin 325 mg daily was effective in patients below 75 years of age, but not in patients above this age. The other trials revealed no effect of aspirin. PMID- 1866812 TI - [Magnesium deficiency and development of late diabetic complications]. AB - Diabetics have a higher prevalence of recurrent angina, myocardial infarction and hypertension compared with healthy individuals. This is partly due to the metabolic control, and partly to the development of nephropathy, but inherited factors also seem to contribute to their development. Another factor, to some extent inherited, could be magnesium-deficiency. Up to 30% of all diabetics suffer from magnesiumdepletion, which in other disease entities has been related to angina pectoris, myocardial infarction, and changes in blood lipids. Furthermore, magnesium-deficiency might be related to the development of hypertension. In diabetes, magnesium-depletion has been linked with the development of retinopathy, and an increase in abortions and malformations in diabetic pregnancies. No intervention trials with magnesium, to elucidate the question of magnesium depletion and diabetic late complications have hitherto been made. No methods for assessing magnesium-status in diabetes are available as yet, to select patients for this type of trial. PMID- 1866813 TI - [Minor head injuries in a Copenhagen district. 1. Epidemiology]. AB - The records of 1,218 males and 743 females admitted to Copenhagen County Hospital in Glostrup between January 1 1985 and December 31 1986 were studied. The mean age was 28.2 years (SD = 20.3 years). The incidence rate was 360 per 100,000 inhabitants per year and was between 30 and 130% larger for males than females (p less than 0.001), the incidence rate was 26% higher in this study as compared to the rate in Denmark as a whole. Patients between 0 and 14 years were most frequently admitted between noon and the early evening hours and those between 15 and 64 years most frequently from late in the afternoon until the early night. The distribution was uniform throughout the week. There was a tendency towards more frequent admissions in the April and July trimesters. 74% of the patients were admitted at hours when the staff was minimal. This category comprised 4.9% of all patients admitted as emergencies to the hospital. The mean hospitalization was 1.6 days (range 1-14 days). Females were hospitalized longer than males (p less than 0.001). Furthermore, hospitalization was significantly longer, the older the patients were (p = 0.005). Patients with minor head trauma constitute a considerable work load in the hospital, especially outside normal working-hours. PMID- 1866815 TI - [Occurrence of athletic injuries among female elite athletic gymnasts]. AB - A questionnaire investigation was undertaken among 18 female Nordic athletic gymnasts in the teams from their respective countries. The median occurrence of injury was three injuries per 1,000 hours (variation 0-7) with uniform distribution between acute and overexertion injuries. The percentage regional localization were: Upper limbs 24%, lower limbs 65% and trunk 11%. In the age group 18-21 years, the frequency of injury was 46% higher than that in the 14-17 year age group and gymnasts with the greatest duration of training had relatively low incidence of injuries (2.7 as compared with 5.2 injuries per 1,000 hours). Treatment consisted of visits to the general practitioner, casualty department and sport specialist or other specialist comprized 16%, 13% and 16% of all the therapeutic contacts. 5% of the injuries involved hospitalization and 50% were not treated by doctors. PMID- 1866814 TI - [Minor head injuries in a Copenhagen district. 2. Causes, simultaneous lesions, alcohol and economic aspects]. AB - In order to elucidate causes, simultaneous lesions, alcohol intoxication and economic aspects of admission of patients with minor head traumas, the records of 1,961 patients admitted in 1985 and 1986 were reviewed. 35% were admitted after traffic accidents, 18% after assaults and 17% because of home accidents. In the age group 30-39 years, 40% of the males were admitted after assaults. 7% sustained fractures of the extremities, 4% facial fractures and 3% and 1% thoracic and abdominal lesions respectively. At least 28% of all patients, more than 50% of the patients admitted during evening- and night hours and 51% of the males between 14 and 65 years were clinically alcohol intoxicated. 1,876 patients were admitted solely for observation, nine developed an intracranial complication, three were operated upon and one died. The bed day expenditure was 2.7 mill. Dkr. (pounds 225,000), and for the entire nation 64.8 mill. Dkr (pounds 5,400,000). The costs for diagnosing one case of intracranial lesion in Denmark were 925.000 Dkr. (approximately pounds 80,000) and 2.1 mill. Dkr. (pounds 180,000) to find the cases requiring treatment (1985 level). PMID- 1866816 TI - [Routine check-ups of patients with breast cancer. Significance of the referral pattern for survival after recurrence]. AB - The clinical course of recurrent breast cancer was compared in 117 patients with recurrence diagnosed at routine follow-up visits and 100 patients with recurrence detected in the interval between two scheduled follow-up visits. The interval recurrences were diagnosed after self-appointments (37 cases), after referral by general practitioners (31 cases) or other departments (32 cases). The two groups of patients were comparable with respect to age, menopausal status, initial stage of disease, and the type of adjuvant systemic therapy. The interval group of patients had a longer recurrence-free interval and also more symptoms than the routine group. The anatomical distribution of metastases was comparable in the two groups. The interval group of patients had a shorter survival after recurrence compared to the routine group (median 16 versus 25 months, p = 0.07). The survival from initial diagnosis was comparable in the two groups (48 versus 58 months, p = 0.67). Using multivariate Cox regression analysis, the influence of interval as compared with routine recurrences was evaluated in relationship to other prognostic variables (initial stage, recurrence-free interval, presence of visceral metastases, number of metastatic sites). In this model, the stage of disease, the recurrence-free interval, and presence of visceral metastases were the only significant independent prognostic factors. PMID- 1866817 TI - [Treatment of corneal abrasion]. AB - Forty patients with corneal epithelial defects were randomized into two groups. Group 1 (twenty patients) were treated with chloramphenicol ointment and an eye patch for six hours followed by chloramphenicol eyedrops six time a day for six days. Group 2 (twenty patients) were treated with chloramphenicol ointment and double eye patches for twenty-four hours as the only treatment. The patients were examined the next day, and again after a week. Two patients defected in group 1 and two patients from group 1 were excluded from the experiment because they failed to improve after three and four days, respectively. Five patients from group 2 defected. Corneal epithelial wound healing was found to be significantly faster in the group treated with double eye patches and the patients' subjective problems in this group were significantly less. (Significant with a probability less than 1%). PMID- 1866818 TI - [Itching in the external ear--a side effect of ear plugs]. AB - The object of this investigation was to assess the frequency of itching in the external auditory meatus in individuals who use hearing aid ear plugs (OP) and, simultaneously, to assess the cause of the itching. Seventy-six of the patients examined consecutively in the audiological department (ages 34-89 years) were questioned about itching and were submitted to an objective ear, nose and throat examination, audiometry and culturing from the external meatus for bacterial and fungal growth. In 20 patients, patch tests were made for allergic reactions from which the ear plugs were made (heat polymerized methyl methacrylate). None of the 20 patients had become sensitized. Itching in the external auditory meatus was found to be a side effect of employment of ear plugs with an incidence of 39% as opposed to only seven in ears without ear plugs (p less than 0.05). The incidence of itching was not reduced in ears with a ventilation channel in the ear plug. In 38% of the itching ears no objective changes were observed and, in the remaining cases, the changes were frequently limited. Potentially pathological bacterial growth was found to be significantly more in ears with ear plugs (1- greater than 16%, p less than 0.05) and in itching ears (4- greater than 24%, p less than 0.05). In ears with potentially pathogenic bacteria, objective changes were nearly always found. In the vast majority of cases, the potentially pathogenic bacteria were Gram-negative, corresponding to the findings in external otitis in the tropics and mixed infections with fungi were frequently present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1866819 TI - [Pericarditis with pericardial tumor-like manifestations in echocardiographic and magnetic resonance examinations]. AB - A case of acute cardiac insufficiency in a 26 year old woman is described. Ultrasound examination of the pericardium was suspect for an pericardial tumor with pericardial effusion and solid masses of tumor in the fluid. Magnetic resonance imaging (MRI) gave the impression of tumor in the pericardium. Pericardiocentesis showed neither malignant cells nor growth of microorganisms. The patient recovered completely on steroid therapy and control MRI showed anatomic normalisation of the cardiac region. It is concluded that idiopatic peracarditis can mimic pericardial tumor on ultrasound and MRI investigation. PMID- 1866821 TI - [A proposal on the structuring of thyroid surgery and patient examination in Denmark]. PMID- 1866820 TI - [Factitious disorder--an iatrogenic disease?]. AB - The case of a woman aged 31 years with numerous contacts with the health care system is reported. The patient presented an extremely varied pattern of complaints with pain as one of the most frequently recurring reasons for admission. During the past 12 to 13 years, the patient was admitted to inpatient units on numerous occasions and was submitted to numerous examinations, most of which revealed normal findings. This article lists a number of possible background causes which might permit a career like this to develop. Measures for prevention of similar "case-stories" in future are discussed. PMID- 1866822 TI - [Iron status and iron supplementation]. PMID- 1866823 TI - [Education in gynecologic and obstetric ultrasound diagnostics]. PMID- 1866824 TI - [Generic prescription]. AB - On the basis of increased interest by the Danish public, not only popularly but also professionally, for generic prescription, a review of the subject is presented. In USA, in particular, pronounced opposition to generic prescription exists from the medical profession and from the drug industry. It is considered that the incitement to develop an original product is weakened. It is feared that marketed "synonymous" product are not always synonymous. Investigation have been carried out to show that generic prescription can function to the satisfaction of everyone and parcticularly the consumers' satisfaction (up to 83% of the patients express satisfaction with arrangement in a Danish investigation). In addition, the system results in an immediate saving (approximately 7%), if it functions. However, at its best, the system functions in only half of the cases in the majority of places, in USA most frequently only in 10% and in England in 36%. The professional groups constitute the greatest obstacle. Doctors, in particular, show great doubts about the advisability of the system. If the system is to function at all, pharmacologists and doctors must be motivated to employ the system correctly. Education is necessary in order to avoid generic prescription involving considerable unpaid extra work for the pharmacist and the doctor. It is essential that the Danish Board of Health can guarantee that synonymous preparations on the market are, in fact, synonymous. Finally, decisions about the extent to which synonymous preparations may be dispensed must lie in the hands of the prescribing doctor who is responsible for the prescription. PMID- 1866825 TI - [Generic prescription/substitution. A 6-month project in a general practice concerning prescription of synonymous preparations]. AB - During a period of six months, two general practitioners with a total of approximately 2,800 Danish National Health Service patients investigated the advantages and disadvantages of generic prescription. Only preparations from Group C (heart and vascular disease) and Group M (bones, joints and muscles) were included. A total of 1,421 prescriptions were issued and synonym preparations were issued for 280 of these. A total of 135 out of 140 possible patients received synonym preparations and 98 (72.6%) out of 135 possible patients replied to a questionnaire sent to them. Out of these 82 (83.7%) were so satisfied with the arrangement that they considered that it should continue. Out of the total of 1,421 prescribed preparations, the savings involved were 6.4% from the Danish National Health Insurance, 4.5% for the communities and 8.4% for the patients. This corresponds to a total saving for Groups M and C of 18,628 Danish crowns (approximately 1,555 pounds) out of the original sum of 278,296 Danish crowns (approximately 23,200 pounds) which corresponds to 6.7%. In Denmark, Groups M and C constitute approximately 25% of all the prescriptions issued. More extensive investigations are recommended to illustrate this subject and before any definite conclusion are drawn. PMID- 1866826 TI - [Schonlein-Henoch syndrome]. AB - Schonlein-Henoch's syndrome is particularly seen between the ages of two and eight years and is twice as frequent in boys as in girls. In up to 80%, symptoms in the form of skin rash, arthritis and abdominalia are observed. The pathognomonic symptom is the skin lesion which most often is confined to the region below the waist and is the first symptom in more than 50%. Incorrect diagnosis particularly of abdominal symptoms may result in unnecessary laparotomy. The etiology and pathogenesis are not yet completely elucidated but it is believed that SHS is caused by an IgA-mediated immune response to a variety of foreign antigens. The treatment and the prophylaxis, particularly concerning the nephropathy, of SHS is still very deficient today. Depending on the nature and the degree of difficulty the treatment is: salicylates, NSAID, prednisone, cytotoxica, plasmapheresis, substitution with factor 13-concentrate and, in terminal renal failure, allotransplantation renis. The course and the prognosis is usually good in cases without nephropathy. In mild cases, the disease lasts a few days, in more serious cases 4-6 weeks with subsequent exacerbations and remissions. Patients who have had SHS-nephritis ought to be followed for at least five years with an annual examination of the blood pressure and urine test for protein and blood. SHS ought to be considered as differential diagnosis in acute cases of abdominal pains, arthralgia, hematuria and CNS-symptoms even if the characteristic skin symptoms are missing. PMID- 1866827 TI - [Surfactant to premature neonates]. AB - Surfactant is a lipoprotein complex which reduces alveolar surface tension, thus reducing the work of respiration. Defective secretion of surfactant in the premature newborn infant gives rise to the respiratory distress syndrome (RDS). Several surfactant preparations, natural (purified) and synthetic, have been evolved. They have been used for prophylaxis and also therapy. Several controlled studies have shown decreased mortality, while the effect on neonatal complications and late results are still uncertain. PMID- 1866828 TI - [Morbidity among mothers and infants after ambulatory deliveries]. AB - Postpartum early discharge programs are reviewed. Few programs were mandatory and both primi- and multiparae were included. Discharge varied from two to 72 hours after delivery. Nearly all programs had prenatal preparation and all patients had postpartum follow-up at home. Approximately one per cent of the infants were readmitted mostly on account of hyperbilirubinemia and infections, and half as many mothers were readmitted mostly for hemorrhage and endometritis. Infants discharged very early were readmitted more frequently than others. There were no statistical significant difference in mortality or morbidity between mothers or infants in early discharge groups and control groups. PMID- 1866829 TI - [Coagulation disorders in traumatic brain injuries]. AB - Exposure of subendothelial collagen and release of tissue thromboplastin render possible activation of both the internal and external coagulation cascades in traumatic lesions of the brain. Disseminated intravascular coagulation (DIC) is well described in brain lesions and may contribute to the haemorrhagic tendency in brain-injured patients. DIC is also suggested as a contributory factor for the degree of secondary brain damage and the development of pulmonary complications and tardive intracranial haematomata. The literature concerning DIC and traumatic brain damage is, however, difficult to assess as many of the materials include multitraumatized patients and the diagnostic criteria for DIC vary. In addition, it is difficult to differentiate between normal physiological phenomena and genuine pathological processes. No controlled and randomized investigations concerning the effects of specific antithrombotic treatment of DIC in traumatic lesions of the brain are available. It is recommended that patients with brain injuries should be examined for the development of disturbances of coagulation and that the relevant laboratory investigations should be included in assessment of this patient group. PMID- 1866830 TI - [Diabetes screening among women who gave birth to heavy infants. The result of 128 glucose tolerance tests during puerperium in women who gave birth to infants weighing 4,500 gram or more, and establishing the screening procedures in Danish maternity clinics]. AB - Experience gained from glucose tolerance tests during the puerperium carried out during a period of two years on 129 non-diabetic mothers who had given birth to infants with birth weights of over 4,500 g is presented. Out of 128 completed investigations, only one new case of diabetes was diagnosed. Seven glucose tolerance tests revealed intolerance and six of these were normal on control. No fasting blood sugar levels were over 6.0 mmol/l. These findings correspond to the frequencies of reduced glucose tolerance in a previously published Danish article. In Denmark as a whole, approximately 60% of these women undergo glucose tolerance tests and further 20% are submitted to fasting blood sugar determinations. Glucose tolerance tests during the puerperium based on postprandial blood sugar measurements for two hours is not considered to be suitable as a screening method for diabetes mellitus. PMID- 1866831 TI - [Consumption of milk among pregnant women and its significance for the intake of calcium and fats]. AB - Out of a total of 158 pregnant women, 55 accepted participation in a dietary investigation for seven days with the object of assessing the consumption of milk by pregnant women and the significance of this for the intake of energy-providing dietary constituents and certain minerals. The diet in pregnant women contained more fat (43.2%) and the relationship between polyunsaturated and saturated fatty acids (P/S-relationship) (0.25) was less than that recommended. The daily dietary content of fibre of 20.7 g/day was lower than the recommended intake. Calcium, phosphate and magnesium intakes constituted 180%, 131% and 64% respectively, of the recommended daily intake. The average intake of milk (buttermilk, skim milk, low fat milk and whole milk) was 482 g/day. The calcium content of the milk constituted, on an average, one third of the total calcium intake. The content of fat and saturated fatty acids in the milk constituted 7% and 10%, respectively, of the total intake. Four of the pregnant women had a daily calcium consumption of less than the recommended intake (1,000 mg/day). The same women had the lowest consumption of milk and energy in the group investigated. The results suggest that the dietary consumption is adequate to cover the calcium requirements. Extra calcium supplements should only be recommended for pregnant women with limited consumption of milk and other milk products. Pregnant women should be advised to take increased quantities of magnesium and to reduce the fat intake. PMID- 1866832 TI - [Vaccination granuloma in the breast region--differential diagnosis]. AB - Vaccination granulomas (VG) caused by injection of aluminum adsorbed vaccines have not been described previously in the breast region. We therefore present eight cases, all in women. None of the small tumors were diagnosed as VG before the operation. PMID- 1866833 TI - [Prognosis of patients with rectal cancer treated in a department of general surgery]. AB - The results of treatment of 355 patients with adenocarcinoma of the rectum treated during the period 1973-1982 in a department for general surgery were compared with the results obtained in other more specialized departments. The 5 year survival rate, corrected for deaths from other causes than cancer of the rectum, was calculated retrospectively to be 35% which was comparable with certain departments. Some highly specialized departments had, however, better results. The postoperative mortality was high (14%). Highly differentiated tumours resulted in better prognoses than poorly differentiated tumours (p less than 0.001). The median age was relatively high (67 years) and relatively many of the patients were men (62%). Patients in whom haemorrhage was the first symptom had better prognoses than patients with other symptoms (p = 0.018). The prognoses were similar regardless of the durations of symptoms. PMID- 1866834 TI - [Emergency prehospitalization treatment of cardiac arrest in the municipality of Copenhagen]. AB - A retrospective study was performed concerning prehospital cardiac arrest. This revealed that 177 consecutive patients received advanced medical resuscitation by an anaesthesiologist at the site of the accident during the period 01.01.1988 31.12.1988. A total of 61 (35%) were admitted to hospital and 24 of these (14%) survived for more than 30 days. All 24 were discharged to their homes without major cerebral sequelae. After one year, 21 were still alive. Compared with the results of previous studies in Copenhagen, this study reveals that the overall survival rate may have improved and that cerebral function after cardiac arrest seems to have been improved by the introduction of prehospital medically staffed ambulances. PMID- 1866835 TI - [Unskilled ultrasound scanning in gynecology and obstetrics can lead to serious risks]. AB - Four cases of ectopic pregnancy were incorrectly diagnosed by ultrasound examination as intrauterine pregnancies. The clinicians involved were biased by the misinterpretation and did not react to the clinical symptoms of ectopic pregnancy. One patient died because of intraperitoneal haemorrhage and some of the other patients were in serious danger. In a fifth case, a midwife examined a pregnant woman with a gestational age of 31 weeks and suspected twin pregnancy. A senior registrar with limited training in ultrasound methods performed an examination and found one foetus. After this examination, the patient was examined clinically on six occasions by midwives and obstetricians but none of these questioned the ultrasound diagnosis. Unfortunately, a twin pregnancy was present. This became apparent when the first twin was delivered and the second twin was in a transverse lie and delivery by Caesarean section was required. The second twin has since developed spastic palsy. These case reports illustrate that young doctors require improved training in ultrasonic diagnostic methods. In addition, clinicians should not rely too much on the results of ultrasound examinations but should also employ their clinical judgement. PMID- 1866837 TI - [Surgical treatment of lung cancer in Denmark]. PMID- 1866836 TI - [Explosion accidents during work with tires and wheel rims]. AB - The object of this work is to draw attention to injuries resulting from explosions caused by work with wheel rims and tyres, the extent of the problem and the safety rules which already exist. Seven illustrative cases are presented. A not inconsiderable but frequently disregarded risk for accidental explosions is present in connection with pumping tyres and repairs of tyres and wheel rims. During the explosions, pressure waves of enormous violence may frequently be released. In connection with four accidental explosions of this type, a total of seven persons were injured. Four of these sustained life-threatening injuries. On the basis of the serious accidents, the authors consider it important to draw attention to the fact that the rules, which exist already and which are aimed primarily at avoiding and possibly limiting the extent of the violent explosive energy, should be brought to the notice of all who work with tyres and wheel rims. PMID- 1866838 TI - [Risk of silicosis caused by building site dust]. PMID- 1866839 TI - Spot-scan imaging of microcrystals of an influenza neuraminidase-antibody fragment complex. AB - Electron micrographs of two-dimensional microcrystals of a complex of an avian influenza virus neuraminidase and an antibody Fab fragment, termed 32/3, have been recorded using the spot-scan method of imaging. The crystals have a large unit cell (159.5 A x 159.5 A x 130.5 A) and a high solvent content (approximately 71% by volume) and are a challenging specimen for testing the spot-scan methodology. Crystalline order was preserved to beyond 4 A resolution as demonstrated by electron diffraction, using an embedding medium of a mixture of glucose and neutral potassium phosphotungstate. Using a Philips C400 computer control system interfaced to an EM420 electron microscope, and with the inclusion of additional software in the system, we have been able to record micrographs at low temperature with a relatively narrow (1500 A diameter) moving beam. There is evidence that the use of such a spot-scan beam reduces the effects of beam induced specimen motion on the quality of micrographs. Conventional low-dose "flood-beam" images showed good isotropic optical diffraction in only 15% of cases whereas 30% of spot-scan images showed good diffraction. The best flood beam images gave phases to only 15 A resolution after computer processing, whereas the best spot-scan images gave phases to 7 A resolution. Electron diffraction patterns were also recorded at low temperature, and the resulting diffraction amplitudes combined with phases from spot-scan images to yield a projection map of the structure. A 7 A resolution projection map of the complex is presented, and is compared with the projection map of the same avian influenza neuraminidase complexed with a different monoclonal Fab fragment, NC41, which has been solved to high resolution by X-ray diffraction. PMID- 1866840 TI - [Medical marketing in the media]. AB - The mass-media monopolize an important part of the lay public attention and intellectual energy and yet physicians do not seem very convinced that they must implicate themselves socially and participate in the education of the general public. Two reasons explain the lack of physicians' participation in the media. These are: the lack of interest and the lack of experience. Yet more and more studies underline the importance for health professionals to make more use of the mass-media in educating, supporting and informing the population on all aspects related to health matters. Thus the medical profession must collaborate more closely with the mass-media. Accordingly, physicians must jump at the opportunity to make every positive action known to the population instead of showing off in the media only their corporative or financial interests. They must also intervene each time that matters related to either health or illness are criticized or denounced in the media. As long as the medical profession is not conscious of the importance of judicious use of the media and of assuring its professional and social credibility, surveys will continue to put physicians in the public eye primarily on an individual basis and only in the last instance as a group. PMID- 1866841 TI - [Transitory loss of memory in middle-aged women: distinguishing between functional and organic disorders. An interview with Dr. Gilbert Fournier]. PMID- 1866843 TI - [Shortage: the heart of the question. An interview with Dr. Denis Hamel, president of the Association of Cardiologists of Quebec]. PMID- 1866842 TI - [Lyme Borreliosis: should we prepare for an epidemic?]. AB - Lyme Borreliosis results from the persistent infection with a spirochete, Borrelia burgdorferi, transmitted by ticks of the Ixodes ricinus complex. The geographic distribution of these ticks depends on specific climatic and ecologic conditions. Lyme borreliosis is a disease with protean manifestations whose distribution is world-wide. In North America, the disease usually begins between May and August with a characteristic rash, erythema chronicum migrans, accompanied by non specific or meningitis-like symptoms. Weeks or months after the rash, the patient may develop transient cardiac, neurologic or musculo skeletal manifestations, and usually more than a year later, some patients have chronic skin, joint, or neurologic manifestations. Antibody titers rise after four to eight weeks in most patients that did not receive antibiotics, and serologic testing then represents the most useful aid in diagnosis. Due to large numbers of false positives, serologic testing should be limited to those patients with strong clinical or epidemiological evidence of the disease. Treatment with appropriate antibiotics, and for adequate time, is usually curative but in later stages patients may need to be retreated and some may not respond. PMID- 1866845 TI - [Antithrombotic agents and coronary disease]. PMID- 1866844 TI - [Role of hyperlipidemia and its treatment]. PMID- 1866847 TI - [Heart rhythms: indications of electrophysiological studies and studies of delayed potentials]. PMID- 1866846 TI - [Intervention cardiology and coronary dilatation]. PMID- 1866848 TI - [Structure and composition of LDL in pathological obesity and diabetes]. PMID- 1866849 TI - [Case report. A 35 year-old-man admitted for fever and diarrhea]. PMID- 1866850 TI - Renal cell carcinoma in young and old patients. Comparison of prognostic pathologic variables (cell type, tumor grade and stage, and DNA ploidy pattern) and their impact on disease outcome. AB - A group of 41 young patients (age less than or equal to 40 years; mean, 35.7 years) and a group of 34 old patients (age greater than or equal to 80 years; mean, 82.4 years) who underwent operation for renal cell carcinoma between 1970 and 1986 were compared. Sex, grade, and DNA ploidy pattern distributions were similar between the groups. Granular cell and papillary cancers with lower stages at presentation were more common among the young. In patients with high-stage disease, 73 percent of the older group but none of the younger had DNA diploid tumors. Low-stage clear cell carcinoma caused cancer death only in the young. Stage I nondiploid clear cell carcinomas were associated with death (33%) only in the young. Overall, death rates seem similar for both groups but among the young most (63%) occurred with low-stage disease and a nondiploid pattern only; among the old, 88 percent occurred with high-stage disease and independent of DNA ploidy pattern. PMID- 1866851 TI - Comprehensive evaluation and treatment of 75 men referred to chronic prostatitis clinic. AB - We investigated the role of genitourinary tract infections, structural and psychologic abnormalities in 75 men referred to a "chronic prostatitis" clinic. Patients had had symptoms for an average of eighty-three months and had received an average of ten weeks of antimicrobial treatment during the three months prior to evaluation. Specific infectious diseases, structural or functional causes were identified in 34 (45%) of the 75 patients. Genitourinary tract pathogens were isolated from 26 patients and inflammation was documented in urethral or prostatic secretions of 24 patients. Structural or functional abnormalities that merited treatment were identified in 8 cases. In addition, major criteria for depression were documented in 9 of 17 patients who agreed to this evaluation. Overall, a comprehensive approach to diagnosis led to specific treatment for 37 (49%) of the 75 men with chronic prostatitis, despite longstanding symptoms and failure of multiple prior courses of therapy. PMID- 1866853 TI - Effects of prostatectomy on sexual function. AB - We evaluated the effects of prostatectomy on sexual function in 210 patients, 49.6 percent of whom underwent transurethral resection of the prostate (TURP), and the remainder had suprapubic transvesical prostatectomy (SPP). Pre- and postoperative interviews with detailed questionnaires were utilized. Postoperative sexual dysfunction was reported by 18 of 152 patients (11.8%) who were functioning normally prior to surgery. The incidence of postoperative impotence was evenly distributed between the TURP and SPP groups and was age related; it was highest among older patients. We further observed a strong correlation between the presence of a permanent sexual partner and the preservation of potency. We conclude that the risk of postoperative impotence is dependent on both the patient's age and the presence of a partner, and should be discussed with the patient preoperatively. PMID- 1866852 TI - Prostate balloon dilatation monitored by transrectal ultrasound. AB - Transrectal prostate ultrasound is helpful as an adjunct in monitoring prostate balloon dilatation using the ASI system. This is a review of the important features of this technique. PMID- 1866854 TI - Mechanical complications associated with mentor inflatable penile prosthesis. AB - The Mentor inflatable penile prosthesis was developed in an attempt to decrease the mechanical failure rate of the various prostheses' components. We herein report on the reliability of the device in 46 men implanted with the Mentor device from December 1982 to June 1987. Prior to manufacturer device modification in 1985, mechanical failure mainly attributable to input tubing cracks occurred in 10 of 30 implantations. Since device improvement in April 1985, the mechanical failure rate has decreased to 4 percent. The Mentor inflatable penile prosthesis has been a mechanically reliable device since design improvement in 1985. PMID- 1866855 TI - Identifying risk factors in development of clinically significant post-shock-wave lithotripsy subcapsular hematomas. AB - A retrospective study of 1,012 shock-wave lithotripsy treatments was performed to identify and analyze the risk factors for the development of six clinically significant post-extracorporeal shock-wave lithotripsy (ESWL) subcapsular hematomas. The patients studied had clinical signs and symptoms that on evaluation were confirmed as originating from a subcapsular hematoma. Common factors identified which we believe may put patients at increased risk for the development of subcapsular hematoma included hypertension, diabetes mellitus, coronary artery disease, and obesity. PMID- 1866857 TI - Correlation of radionuclide urodynamometric and clinical data in 20 men with urinary symptoms. AB - Radionuclide uroflowmetry was performed in 20 patients. These data were correlated with other urologic data, the treatment decision, and the patient's clinical status five to twelve months after testing. In 19 patients the follow-up period confirmed the expectations of the therapeutic plan. We conclude that the radionuclide uroflowmetry technique provides the urologist with objective data which can assist in the decision to perform surgery. PMID- 1866856 TI - Relationship between use of diuretics and continence status in the elderly. AB - Although diuretics have been implicated as a cause of urinary incontinence, no evidence has been presented prior to this report to confirm such a relationship. Our epidemiologic survey of 1,956 respondents sixty years of age and older in Washtenaw County, Michigan, revealed 24.6 percent of men and 36.9 percent of women were current users of a diuretic medication. Comparisons between users and non-users of diuretics and continence and incontinence status revealed no significant difference in the prevalence of incontinence in either gender. However, when male respondents who had cystometric examinations were analyzed, it was found that diuretic users who have uninhibited detrusor contractions (UDC) had a significantly higher prevalence of urinary incontinence (85.7%) when compared with non-users with UDC (25%) (p = 0.009). Among men who did not have UDC, use or non-use of diuretics showed a similar relationship but did not reach statistical significance (p = 0.085). There were too few female respondents with UDC to make meaningful analysis in this group. PMID- 1866858 TI - Extracorporeal shock-wave lithotripsy: capital investment decision. PMID- 1866859 TI - ESWL treatment with ventral shock-wave application: therapy of iliac and distal ureteral calculi. AB - Because of the interposition of bony structures, extracorporeal shock-wave lithotripsy (ESWL) of middle or iliac ureteral calculi is not feasible in the conventional supine position. By a slight modification of the patient's couch allowing the prone positioning of the patient, 22 patients with calculi covered by bony structures were thus treated. The success rate of 95 percent without complications is promising and renders ESWL therapy as an alternative to ureteroscopic extraction of mid and iliac ureteral calculi. PMID- 1866860 TI - Posterior urethral valves presenting as venous obstruction. AB - A patient with posterior urethral valves presented with unilateral lower leg ecchymosis and edema. He initially had significant renal function impairment. The ecchymosis and edema resolved after appropriate therapy, and his renal function returned to normal. PMID- 1866861 TI - Recombinant alpha interferon in metastatic renal cell carcinoma. A cooperative phase II study. AB - A total of 61 evaluable patients with advanced renal cell carcinoma have been treated with 3 x 10(6) IU per square meter of body surface with recombinant alpha 2b interferon three times a week within a Cooperative Phase II Study. Toxic death for terminal renal failure occurred in 1 patient (1.63%), and toxicities greater than WHO grade 2 were present in 10 cases (16%). The overall response rate after six months of treatment was 13.1% (partial response 4, minor response 4). Two complete responses were obtained at nine and fifteen months (3.3%). Long-lasting stabilization of disease was 13.1 percent. PMID- 1866862 TI - Birch-Miller electrotest needle: aid to local anesthetic endoscopic surgery. PMID- 1866863 TI - Self-retaining follower for urethral strictures. PMID- 1866864 TI - Perirenal lipoma versus renal cell carcinoma. AB - Pure renal and perirenal lipomas are rare. They arise from renal cortex, capsule, or perirenal tissue, and may be difficult to distinguish from renal adenocarcinomas. We report on a patient who presented with a renal mass that had the radiologic findings suggestive of a renal cell carcinoma, but proved to be a simple lipoma. PMID- 1866865 TI - Squamous metaplasia in hormonally treated prostatic cancer. Significance during follow-up. AB - A prospective study of 59 hormonally treated prostatic cancer cases was undertaken during follow-up with sequential transrectal palpation and fine-needle aspiration. At initiation of therapy patients' ages ranged from forty-eight to eighty-two years (median, 68 years). The usual follow-up interval was 6 +/- 3 months, and follow-up periods ranged from six months to one hundred twenty months (median 48 months). The cytologic findings were categorized under four cytologic response types and palpation findings under five response grades. Four different degrees of squamous metaplasia (1+, 2+, 3+, 4+) were observed in smears, depending on semiquantitative determination of squamous metaplastic cells in relation to the total amount of benign and malignant epithelial cells in the smear. There were 341 follow-up observations in which both transrectal fine needle aspiration cytology and palpation were done. In 306 of these, cytologic findings were found to be adequate. Comparison of squamous metaplasia with cytologic response types revealed a highly significant difference between the benign state and recurrence/frank malignancy. This was also true when frequency of squamous metaplasia was compared with palpatory response grades. It was found that squamous metaplasia can be a valuable adjunct to other cytomorphologic changes such as shrinkage of tumor cell size and decrease in size of nucleoli or its disappearance, in determining response to hormonal therapy. PMID- 1866866 TI - Paraganglioma of urethra. AB - Paraganglioma of the urethra is a rare tumor; only 4 cases have been reported previously. We report a fifth case of urethral paraganglioma and review the literature. PMID- 1866867 TI - Extravaginal torsion of spermatic cord in adult. AB - A twenty-six-year-old man with no history of testicular trauma presented with both extra- and intravaginal torsion of the spermatic cord. This phenomenon is extremely rare in the adult, having been reported only twice before. PMID- 1866868 TI - Intrarenal pancreatic cyst. AB - A case report of intrarenal true cyst of the pancreas is presented. The patient presented with flank pain. Her diabetes and hypertension were well-controlled. The cause of the pain was presumed to be a cystic renal mass, which proved to be of pancreatic origin only after the pathologic confirmation from the nephrectomy specimen. PMID- 1866869 TI - Ciprofloxacin versus gentamicin in prophylaxis against bacteremia in transrectal prostate needle biopsy. AB - Consecutive patients with abnormal rectal examinations underwent transrectal needle prostate biopsy at VA Medical Center, New Orleans. Each patient was randomized to receive either gentamicin 1.5 mg/kg intravenously (IV) or 500 mg ciprofloxacin (Cipro-Miles) p.o., before and after the biopsy. Serum and prostate tissue levels of ciprofloxacin and gentamicin were measured by high-pressure liquid chromatography and by competitive binding immunoassay, respectively. Blood cultures were obtained, and the patients were observed for twenty-four hours after biopsy. After discharge the patients were followed up by telephone. The incidence of bacteremia and postbiopsy symptoms were less with ciprofloxacin. Prostate tissue levels of this drug were higher than gentamicin, while serum levels were roughly equivalent. Ciprofloxacin is less nephrotoxic, can be given orally, and has a better antimicrobial spectrum. We, therefore, recommend it as prophylaxis against bacteremia in transrectal prostate needle biopsy. Furthermore, it appears that prostatic drug levels are more important than serum levels in preventing bacteremia. PMID- 1866870 TI - Effect of radiation combined with hyperthermia on human prostatic carcinoma cell lines in culture. AB - The effect of radiation combined with heat on three human prostatic carcinoma cell lines growing in vitro was investigated. Cells were exposed to different radiation doses followed by heat treatment at 43 degrees C for one hour. Heat treatment, given ten minutes after radiation, significantly enhanced the radiation response of all the cell lines studied. The combined effect of radiation and heat produced greater cytotoxicity than predicted from the additive effects of the two individual treatment modalities alone. These results indicate that a combined treatment regimen of radiation plus hyperthermia (43 degrees, 1 hr) might be an important tool in maintaining a better local control of prostatic cancer. PMID- 1866871 TI - Hormonally refractory prostate cancer. PMID- 1866872 TI - Absent communication between cavernous bodies: a real possibility. PMID- 1866874 TI - International disease surveillance. Quarterly report January to March 1991. PMID- 1866875 TI - B-mode real time ultrasonographic imaging of the testis and epididymis of sheep and goats. AB - Ten male goats and five rams were examined from 11 and 15 weeks of age, respectively, for six months to study the ultrasonic appearance of normal testes and epididymides before and after puberty. Five adult rams with lesions of these organs were also examined. A portable, B-mode, real time scanner fitted with a 7.5 MHz, linear array transducer was used. The testis appeared as a homogeneous and moderately echogenic structure with a centrally located mediastinum testis represented by an hyperechogenic line in images taken in the longitudinal plane and by an almost circular spot in transverse images. The testicular capsule and skin were evident as a distinct hyperechogenic line encircling the testicular parenchyma. A thin non-echogenic layer of fluid, presumably between two layers of tunica vaginalis, was observed. The tail of the epididymis was more heterogeneous and less echogenic than the testis. The epididymal head was also less echogenic but homogeneous in texture, and the body of the epididymis was difficult to image. The pampiniform plexus was easily identified as numerous convoluted sonolucent tubular structures. The ultrasonic images of possible cases of epididymitis, spermatocele, testicular cyst and abscess and scrotal hernia are described. PMID- 1866873 TI - Appendiceal abscess and urinary retention. PMID- 1866877 TI - 'Clearview' rapid test compared with other methods to diagnose chlamydial infection. PMID- 1866876 TI - Development of LYNX: a computer application for disease diagnosis and health monitoring in wild mammals, birds and reptiles. AB - IBM-compatible software has been developed so that quantitative and qualitative haematological and biochemical reference data for over 500 species of mammals, birds and reptiles can be made readily accessible to veterinary surgeons. The LYNX software makes it possible to retrieve these data at different taxonomic levels (species, genera, families, orders and classes) and to select data by age and sex. The data for each variable may be presented in the form of a reference range or as a frequency histogram. Notes describing the variations in blood cell morphology observed in healthy individuals of each species are included in the database. The user's own haematological and biochemical data can also be entered, stored and used. PMID- 1866878 TI - Closure of veterinary investigation centres. PMID- 1866879 TI - Companion animal medicines and EC legislation. PMID- 1866880 TI - Identification of subclinical mastitis with a hand-held electrical conductivity meter. AB - A hand-held, commercially available instrument for measuring the electrical conductivity of milk (the Milk Checker) has been examined for its usefulness and accuracy in detecting subclinical and clinical mastitis. Foremilk from uninfected quarters had an electrical conductivity of 5.4 to 5.6 millisiemens (mS)/cm. Milk from cows with subclinical Staphylococcus aureus infections had a higher milk conductivity (7.1 to 7.5 mS/cm) but milk from cows with subclinical S uberis infections showed no increase in conductivity (5.3 to 5.6 mS/cm). However, experimental S uberis infections could be detected by a 50 per cent increase in the electrical conductivity of foremilk two milkings before visible signs of mastitis were apparent. The equipment could be a useful advisory/veterinary tool but is unlikely to be used routinely in the milking parlour. PMID- 1866881 TI - Head trauma in two horses. AB - The initial clinical signs displayed by two horses with head trauma are described and related to the pathology and management of the condition, to illustrate the diversity of signs that may result from similar events. It is suggested that careful repeated neurological investigations are more reliable prognostic indicators in cases of equine head trauma than a reliance on the initial assessment. PMID- 1866882 TI - Premature expulsion of the placenta and bovine perinatal mortality. AB - In one study two cases of premature expulsion of the placenta were recorded among 60 supervised calvings (3.3 per cent); both calves died. In a second study, 47 cases were recorded among 332 cases of perinatal mortality (14.2 per cent). The condition was associated with fetal malpresentation and malposture, and mortality either before or during parturition. There was no significant relationship between the occurrence of premature expulsion of the placenta and parity, calving difficulty, previous calving history or the sex of the calf. The condition in cattle is compared with placenta praevia in women. PMID- 1866883 TI - Canine dysautonomia: a case report. PMID- 1866885 TI - Control of fighting dogs. PMID- 1866884 TI - Serum fructosamine in ovine pregnancy toxaemia: a possible prognostic index. PMID- 1866886 TI - Use of animals in research. PMID- 1866887 TI - Euthanasia of chickens. PMID- 1866888 TI - Feline spongiform encephalopathy. PMID- 1866890 TI - Vets, cats and pain. PMID- 1866889 TI - Unilateral inguinal scrotal hernia in a castrated dog. PMID- 1866891 TI - Antibodies to iron-regulated outer membrane proteins of coliform bacteria isolated from bovine intramammary infections. AB - Expression of iron-regulated outer membrane proteins (OMP) by Escherichia coli and Klebsiella pneumoniae initially isolated from bovine intramammary infections (IMI) was investigated. Additionally, the presence of antibodies in bovine serum and mammary secretion directed against the iron-regulated OMP was examined. Outer membrane proteins were separated by sodium-dodecyl polyacrylamide electrophoresis. Detection of immunoglobulin G directed against OMP was by immunoblotting. All Gram-negative bacteria expressed iron-regulated OMP when grown in skim milk or trypticase soy broth plus iron chelator, alpha-alpha' dipyridyl. Immunoglobulin G directed against the iron-regulated OMP, as well as the major OMP and several other proteins, was detected in serum and milk of lactating cows with or without Gram-negative bacterial IMI. Antibody against the iron-regulated OMP was detected also in colostrum, secretion from the involuted gland, and in newborn calf serum 4 days after ingesting colostrum. PMID- 1866892 TI - In vitro effects of prepartum concentrations of oestradiol-17 beta on cell mediated immunity and phagocytosis by porcine leukocytes. AB - The in vitro effect of oestradiol-17 beta (Oe2) on cell-mediated immunity (CMI) and phagocytosis by leukocytes obtained from ten and eight sows, respectively, was studied. The concentrations of Oe2 used were 300 pmol/l and 3000 pmol/l, to reflect a low and a high prepartum concentration of the hormone. The CMI was measured by lymphocyte proliferation (LP) tests performed on whole blood and purified mononuclear cells (MNC) and by estimation of the production of interleukin-2 (IL-2) in the latter type of culture. In the whole blood LP test, the mitotic response to concanavalin A (Con A) was increased by 29% (P less than or equal to 0.05) when the Oe2 concentration was 300 pmol/l. The higher concentration of Oe2 (3000 pmol/l) increased the amount of IL-2 in supernatants from Con A-stimulated MNC by 17% (P less than or equal to 0.05). The phagocytic function of polymorphonuclear leukocytes was determined in a chemiluminescence assay. In this assay, the maximal rate of phagocytosis was reduced by 12% (P less than or equal to 0.01) and the area under the curve by 10% (P less than or equal to 0.05) at an Oe2 concentration of 3000 pmol/l. The results show that prepartum concentrations of Oe2 can promote CMI in vitro, but weaken phagocytosis by porcine leukocytes. PMID- 1866893 TI - Pasteurella haemolytica A1 purified capsular polysaccharide does not stimulate interleukin-1 and tumor necrosis factor release by bovine monocytes and alveolar macrophages. AB - Purified capsular polysaccharide (CPS) stimulated significant release of interleukin-1 (IL-1) activity from bovine blood monocytes but not alveolar macrophages in vitro. The ability of CPS to induce IL-1 release was resistant to boiling and inhibited by the addition of polymyxin beta. Thus, it is likely that the IL-1 release stimulated by CPS resulted from the small amount of contaminating lipopolysaccharide (LPS) that was present (an estimated 5 pg LPS per microgram CPS) rather than to a direct effect of CPS. Tumor necrosis factor activity was not detected in the culture supernatants of bovine monocytes incubated with purified CPS for 1-18 h in vitro. PMID- 1866894 TI - Testosterone induces lymphopenia in turtles. AB - Owing to the possible role of sex steroids in the immune-neuroendocrine interactions found in lower vertebrates, we attempted to delineate the effect of testosterone propionate on peripheral blood (PB) and the lymphoid organs of the turtle Mauremys caspica. A single intraperitoneal injection of 200 micrograms/g body weight produced thymic involution and intense lymphopenia in the spleen and, less severely, in the PB compartment. It is suggested that lymphocyte redistribution may occur among the various compartments of the body as the main effect of hormone-induced lymphocyte redistribution, although the mechanism in reptiles and mammals is not yet understood. PMID- 1866896 TI - [The clinical manifestations in karakurt spider bites]. PMID- 1866895 TI - Abnormal cutaneous response to mitogens and a contact allergen in dogs with atopic dermatitis. AB - Antigen specific and nonspecific T-lymphocyte activity was evaluated in normal dogs and in dogs with atopic dermatitis by measuring the increase in skin thickness after application of the contact allergen dinitrochlorobenzene and after intradermal injection of the mitogens phytohemagglutinin and concanavalin A. The atopic dogs had a significantly reduced response to the contact allergen (P less than or equal to 0.001) but a significantly increased response to the mitogens (P less than or equal to 0.001). The atopic and normal dogs responded similarly to intradermally injected histamine. The response of dogs with non atopic skin conditions to the cutaneous mitogen test was like that of normal dogs. Pre-existing dermatitis does not apparently influence cutaneous response to mitogens in dogs. The cutaneous response of atopics during treatment with corticosteroids is not different from normal controls. These results suggest a role for altered cell-mediated immunity in the pathogenesis of canine atopy and that the cutaneous mitogen test may have value as a rapid screening test for the disease. PMID- 1866897 TI - [The Stevens-Johnson syndrome]. PMID- 1866898 TI - [Percutaneous nephrostomy as a method for the temporary supravesical diversion of the urine]. PMID- 1866899 TI - [Biliary ileus]. PMID- 1866900 TI - [The teaching of the "Vascular Diseases of the Nervous System" unit for medical institute students]. PMID- 1866901 TI - [The dispensary care of cardiology patients in a rural locality based on selective sampling data]. PMID- 1866902 TI - [The therapeutic problems of the heart transplant]. PMID- 1866904 TI - [The scientific and pedagogic activities of Academician F. G. Ianovskii]. PMID- 1866903 TI - [The organization of epidemiological surveillance over measles in Rovno Province]. PMID- 1866905 TI - [The School Chronicle of prof. V. P. Krylov--a scientific literary memorial to pathological anatomy]. PMID- 1866906 TI - [The pharmacodynamics of hepatic protectors from the lady's-thistle (Silybum marianum)]. PMID- 1866907 TI - [The use of helium-oxygen mixtures]. PMID- 1866908 TI - [Oxalic acid metabolic disorder in kidney diseases]. PMID- 1866909 TI - [Diseases of the heart muscle]. PMID- 1866910 TI - [Erythrocyte acid resistance in the drug treatment of heart failure in patients with ischemic heart disease]. PMID- 1866912 TI - [Hemosorption in the combined treatment of acute 1,2-dichloroethane poisonings]. AB - Carbon hemosorption was carried out in 41 patients suffering of 1,2-dichlorethane intoxication (acute). Complex methods of therapy included also methods of potentiation of natural processes of detoxication, enterosorption, specific antidote treatment with acetylcysteine and vitamin E. Use of hemosorption favoured essential reduction of lethality, decrease of the number of severe complications (exotoxic shock, hepatopathy). PMID- 1866911 TI - [Dynamic anti-Proteus immunity in plasma donors during plasmapheresis]. AB - A study is presented of homeostasis in 18 volunteer donors after immunisation with Proteus vaccine and in the dynamics of subsequent plasmapheresis for 12 months. It was shown that as a result of anti-Proteus immunisation there occurs an increase of the titer of anti-Proteus antibodies in the blood serum which was maintained at a high level in the course of plasmapheresis for three months. Indices of the peripheral blood, urine, liver function, humoral unspecific and cellular immunity were within normal levels. The blood of donors immunized with Proteus vaccine is a source of obtaining anti-Proteus plasma--an immune allogenous preparation for complex treatment of patients with severe forms of diseases of Proteus etiology. PMID- 1866913 TI - [The dynamics of the arterial pressure in patients with aortic coarctation before and after surgery]. AB - The arterial pressure was evaluated in 841 patients before surgery and for 3-23 years after operative correction of coarctation of the aorta. It was established that the level of preoperative arterial pressure depended on the degree of congenital aortal stenosis and secondary changes of the cardiovascular system which deteriorate during the adult years. It was found that in the postoperative period even in the absence of aortal recoarctation a certain part of patients develops again the hypertensive syndrome. The number of these patients increases with increase of observation time. The efficacy of the operation depended on the age of the patient and level of hypertension by the time of surgery. PMID- 1866914 TI - [Glucose-6-phosphate dehydrogenase activity in patients with chronic inflammatory lung diseases]. AB - The activity of the key enzyme of the pentoso-phosphate cycle--glucoso-6 phosphatedehydrogenase was examined in patients with chronic inflammatory pulmonary diseases. Results indicate that with exacerbation of the process in the bronchopulmonary system there occurs an increase of the activity of the mentioned enzyme. Examination of the activity of this enzyme may be of value for optimization of treatment measures in patients with inflammatory pulmonary diseases. PMID- 1866915 TI - [The results of pneumothermometry and mucociliary clearance study in pulmonary tuberculosis patients]. AB - Pneumothermometry was carried out in 136 patients with different forms of pulmonary tuberculosis. It was found that the temperature of the alveolar air in pulmonary tuberculosis patients depended on the character of the specific process on a lesser degree than on the spread of the process. The temperature of the exhaled alveolar air was most reduced in patients suffering of spread pulmonary tuberculosis with marked fibrosis of the pulmonary tissue. Disorders of the drainage function of the bronchi reflected mostly the character of the specific lesion of the pulmonary tissue and was most pronounced in patients with fibrous cavernous cirrhotic tuberculosis. PMID- 1866916 TI - [The validation of the use of thymic preparations in tuberculous infection by experimental data]. PMID- 1866917 TI - [The status of general and local humoral immunity in patients with peptic ulcer and chronic gastroduodenitis]. AB - The content of secretory immunoglobulins A and serum immunoglobulins A, M, G, D in the blood serum and biological. fluids (saliva, gastric juice and duodenal contents) was examined in 108 patients with gastric and duodenal ulcer and in 68 patients with chronic gastroduodenitis. The obtained data evidence tense states of the general and local humoral immunity in all patients with gastric and duodenal ulcer and chronic gastroduodenitis. Monotypical changes in patients with diseases of the gastroduodenal zone, apparently, reflect the participation of the immunological component of the ulcerogenic situation already at the stage of preulcer condition. PMID- 1866918 TI - [The effect of hypnotic suggestion and millimeter-range electromagnetic radiation on the clinical and endoscopic indices in peptic ulcer patients]. AB - The authors studied the effect of microwave resonance therapy, hypnosuggestion and their combinations on the dynamics of clinico-endoscopic indices in 182 patients with duodenal ulcer. It was established that these methods were highly effective allowing to control rapidly the pain syndrome, to achieve complete healing of the ulcer in 70-95% of cases within 14.8-16.7 days. The results were best when the two methods were combined. PMID- 1866919 TI - [Gastric and duodenal functions in patients who have undergone cholecystectomy]. AB - The authors examined 105 patients with postcholecystectomy syndrome. It was established that with increase of time following cholecystectomy manifestations of chronic duodenal obstruction show an advance. This results in an increase of the incidence of patients with gastroduodenal reflux and reduced acid-forming function of the stomach. PMID- 1866920 TI - [The level of beta-endorphins in patients with chronic active hepatitis]. PMID- 1866921 TI - [The characteristics of the clinical course of hereditary hemochromatosis]. AB - The authors describe 32 patients with hemochromatosis observed from 1965 through 1990 (28 men and 4 women). The diagnostic role of serum iron determination and liver biopsy is emphasized. The therapeutic results of bloodletting (500 ml weekly for several years) dyspheral (1-1.2 g intramuscularly daily for 1-2 years and longer). This treatment did not essentially influence the course of diabetes mellitus, liver cirrhosis as well as the articular and endocrine syndromes. The clinical effect of this treatment lasted for 6-8 years. PMID- 1866922 TI - [The fibrinolysis system in diabetic glomerulosclerosis]. AB - It was found that patients with diabetic glomerulosclerosis showed an increased intensity of blood coagulation as well as essential diverse changes in the system of fibrinolysis. These changes were more pronounced in patients suffering of diabetes mellitus than in the diabetic patients without glomerulosclerosis. It is recommended to introduce into clinical practice the Lejen method with the purpose of determining indications to heparin therapy and dynamic control of patients during treatment with anticoagulants. PMID- 1866923 TI - [Birefringent fat bodies in the urine of patients with primary and secondary glomerulonephritis]. AB - Results are presented of an investigation of birefracting fatty bodies in the urine of patients with primary chronic lupoid and Henoch glomerulonephritis. There was a close correlation between the presence of birefracting fatty bodies and severity of glomerulonephritis independent of the morphological picture of the disease and state of renal function. Reduction of the activity of the disease in the course of pathogenetic treatment characterized by a decrease or disappearance of proteinuria was accompanied by a distinct reduction of the level of birefracting fatty bodies or their disappearance. PMID- 1866924 TI - [The anatomy of human kidneys in ultrasonic study]. AB - Ultrasonic examination of the kidneys was carried out in 1026 persons without renal disease. The authors describe the approaches, methods used for examination of the kidneys, convenient for studying the renal parenchyma, kidney pelvis, renal vessels. Data are reported on the possibilities of echography in studying the position, displacement of the kidneys, their sizes, structure and sizes of the renal pyramids, renal columns, calyces, kidney pelvis, renal veins and arteries. PMID- 1866926 TI - [Nonspecific active immunotherapy in the combined treatment of malignant neoplasms]. PMID- 1866925 TI - [The clinical significance of the morphofunctional status of the neutrophilic granulocytes in the palatine tonsils of angina patients]. AB - The morphofunctional state of neutrophils of the palatine tonsils and peripheral blood was studied by means of the lysosomal-cationic test (LCT) in 73 patients with primary streptococcal angina. It is concluded that the LCT test may be used for objective evaluation of the severity of angina and its treatment efficacy. PMID- 1866927 TI - [Circulating immune complexes and neutrophilic phagocytic function in patients with idiopathic autoimmune thrombocytopenic purpura]. AB - The concentration of circulating immune complexes, serum immunoglobulins and state of phagocytic function of neutrophils was studied in patients with autoimmune thrombocytopenic purpura. The patients showed a significant increase of the levels of circulating immune complexes, content of Ig M and Ig G, an increase of the phagocytic activity of neutrophils at the stage of migration, adhesion and absorption of the heterogeneous. The revealed disorders of phagocytic function and destruction of granulocytes at the stage of digestion may be explained by increased load on the phagocytic neutrophils due to the main pathologic process. PMID- 1866928 TI - [The toxicity of the "C", "M" and "P" brands of polyvinyl chloride plastisols used for making medical articles]. AB - It is concluded that polyvinyl plastisols of the mentioned brands should not be used for manufacturing medical products. Only the P brand may be employed for manufacturing balloons for measurement of the blood pressure and for inhalers. PMID- 1866930 TI - [Phototherapy and sleep deprivation as additional methods of treating bronchial asthma patients]. AB - Correction of internal desynchronosis in bronchial asthma by means of phototherapy and partial sleep deprivation was instituted in 4 hormone-dependent patients with bronchial asthma for 13 months. The results were positive: the frequency and severity of night attacks reduced, the condition of the patients improved. PMID- 1866929 TI - [The effect of tobacco smoking on tissue oxygen balance]. AB - Oxygen tension (pO2) in the muscles was studied in 90 healthy young males: 60 were tobacco (cigarette) smokers and 30 were non-smokers. In the smokers pO2 in the muscles was higher than in the non-smokers. Functional tests revealed worsening of O2 to the tissues and reduced tissue metabolism intensity. The latter occurred against the background of quantitative and qualitative compensatory reactions of pO2 regulation mechanisms directed for improvement of O2 transport and tissue aeration indicating a negative effect of smoking on the capacity of tissue cells to utilize O2 in aerobic breathing. PMID- 1866931 TI - [The principles of phytotherapy]. PMID- 1866932 TI - [The use of the sauna for disease prevention in the workers of enterprises with chemical and physical occupational hazards]. AB - It was found that being a hygienic procedure sauna essentially improves well being of the workers, activates the cardiovascular system and mechanism of general adaptation of the body. Sauna increased excretion with sweat fluid of toxic substances (lead, thiuram, captax, sulphenamide C) that penetrated the body during work. Sauna is recommended as an effective procedure in conditions where chemical and physical factors are the leading professional noxae. PMID- 1866933 TI - [Variants in the manifestations of the generalized form of yersiniosis]. AB - The clinical manifestations of generalized yersiniosis were studied in 61 patients. Primary generalized form was observed in 18 patients. Predecessors were gastroenteritis, appendicular syndrome. Clinical manifestations were polymorphous. All patients revealed fever and exanthema, 5%--catarrhal phenomena, 63.3%--lymphadenitis, 86%--arthralgia, 39.2%--gastrointestinal disorders, 114%- icteric syndrome. In 7.6% the course was protracted with recurrences of fever, exanthema, jaundice, diarrhea, formation of arthritis, Reiter's syndrome. Antibacterial treatment was carried out by aminoglycosides, cephalosporins. PMID- 1866934 TI - [The effect of acupuncture on the psychosomatic status of peptic ulcer patients]. AB - A study of the psychosomatic effects of acupuncture treatment of ulcer diseases indicates that a course of acupuncture procedures provides psychological rehabilitation of these patients and results in significant improvement of the functional indices of the gastroduodenal system. It is supposed that acupuncture influences the general mechanisms of ulcer disease pathogenesis, normalizes the cortico-hypothalamo-visceral relations. PMID- 1866935 TI - Health access report. Single payor systems. PMID- 1866936 TI - Bringing politics to the bedside. PMID- 1866937 TI - Health access report. Universal access and health care rationing. PMID- 1866938 TI - JCAHO issues new nursing care standards for hospitals. PMID- 1866940 TI - Health access report. Managed care. PMID- 1866939 TI - Nursing at its best. PMID- 1866941 TI - [Two biotin-labeled probes of gentamicin resistance genes]. AB - A 2.0 kb BamHI-HindIII fragment of pDG0103 from Australia containing gentamicin 2"-o-adenylytransferase [ANT(2")] gene and a 4.9 kb PstI-EcoRI fragment of pBY102 were recovered from low-temperature-melting agarose by the slot method. Both fragments were labeled with biotin-7-dATP by nick translation with a commercial kit. The result of colony and Southern hybridization was that: the 2.0 kb probe from Australia hybridized with that containing ANT(2") from America, while no hybridization occurred between the 2.0 kb probe and the 4.9 kb probe constructed in our lab. Furthermore, the above two fragments were used as probes for detection of 106 strains of gentamicin resistant Enterobacteriaceae. It revealed that there were more than one gentamicin resistance gene in the tested strains. PMID- 1866942 TI - [Isolation and characteristics of Borrelia burgdorferi from Ixodes persulcatus]. AB - We reported the detailed characteristics of Lyme disease spirochetes (Borrelia burgdorferi), strain H7, isolated from Ixodes persulcatus in Heilongjiang. Cells of strain H7 were 9.8--26.5 microns long and 0.13--0.35 microns wide. There were 1--11 waves with a wavelength of 1.2--3.0 microns and an amplitude of 0.59--1.13 microns. Direction of spires was left. Seven flagella were inserted subterminally at each end of the cell and ends were pointed. 31 degrees C was the optimum cultural temperature in vitro. The major constitutional and antigenic proteins were 21k, 32k and 34k proteins. H7 could react on the patient sera of Xinjiang and Heilongjiang with IFA and western blot. These findings demonstrated that strain H7 belonged to species Borrelia burgdorferi, but was a new "subtype" which differed from the strains isolated from other areas and vectors. PMID- 1866944 TI - Rehabilitation medicine--adding life to years. PMID- 1866943 TI - [Isolation of bilirubin oxidase from Myrothecium verrucaria and the optimum conditions of enzyme production]. AB - A bilirubin oxidase (EC 1.3.3.5) producing strain, Mv 2.1089, was isolated from several strains of Myrothecium verrucaria by dilution method. The optimum conditions of enzyme production were investigated and the results were as follows: the suitable medium was cultured at 25 degrees C on a rotating shaker glucose and peptone, at pH 6.0. The strain was cultured at 25 degrees C on a rotating shaker (150 r/min) for 96 h. Bilirubin oxidase with 0.5-1.5 u/ml was obtained in the culture medium. PMID- 1866945 TI - Pain centers--organization and outcome. AB - Pain treatment centers have evolved at a rapid rate, but they differ in their complexity and services provided. Patients, as well as primary care physicians, have difficulty in identifying the appropriate center for a specific problem. Guidelines for pain centers have recently been proposed by the International Association for the Study of Pain, along with an attempt at their accreditation. Outcome studies from pain centers have proliferated, with a wide range of treatment programs being reported. Comprehensive multidisciplinary pain centers using the rehabilitation medicine approach are effective in decreasing disability and increasing the productivity of patients with chronic, disabling pain. PMID- 1866946 TI - Use it or lose it--the hazards of bed rest and inactivity. AB - Professional experience and lay wisdom teach us the benefits of exercise and the hazards of idleness. Yet the myth persists that "bed rest is good for you" when ill or convalescing. Abundant scientific evidence in the past 50 years has demonstrated the specific damage done to each of the body's organ systems by inactivity. Both aging and inactivity lead to strikingly similar kinds of deterioration. I summarize the data from military and veterans' hospitals, rehabilitation experience, aerospace research, and gerontology and review the physiologic and metabolic changes of aging and inactivity, along with strategies to help prevent the iatrogenic complications of bed rest. PMID- 1866947 TI - Rehabilitation in rheumatic diseases. What's new. AB - In the past decade, considerable change has occurred in concepts of rehabilitation in patients with rheumatic diseases. This includes approaches to functional assessment and outcome, new concepts in exercise, and new orthotics. PMID- 1866948 TI - Human immunodeficiency virus infection and diffuse polyneuropathy. Implications for rehabilitation medicine. AB - Patients at various stages of human immunodeficiency virus (HIV) infection require rehabilitation services. These patients present problems for each of the disciplines in a rehabilitation team, and all team members must confront the psychosocial and ethical issues involved with the disease. Patients with HIV infection may have polyneuropathy with multisystem involvement, including dysphagia, autonomic dysfunction, respiratory failure, bowel and bladder dysfunction, generalized weakness, a painful sensory neuropathy, and depression. Guidelines are presented for determining if inpatient rehabilitation or other settings are appropriate. Case management is a valuable strategy for the rehabilitation of patients with this complicated disorder. PMID- 1866949 TI - Low vision rehabilitation. Finding capable people behind damaged eyeballs. AB - Loss of vision is a common physical impairment in America today. Comprehensive low vision rehabilitation programs can have dramatic results in increasing the independence and productivity of affected persons. Rehabilitation efforts must be tailored to the type of vision loss and to specific functional implications. Every effort should be made to enhance the residual vision. Activities of daily living, orientation and mobility, and psychological concerns must be addressed. PMID- 1866950 TI - Postpolio syndrome and cardiopulmonary conditioning. AB - Postpolio syndrome is a group of related signs and symptoms occurring in people who had paralytic poliomyelitis years earlier. New weakness, fatigue, poor endurance, pain, reduced mobility, increased breathing difficulty, intolerance to cold, and sleep disturbance in various degrees and expressions make up the syndrome. The reported incidence is between 25% and 80%. The origins are multifactorial and can be associated with underexertion, overexertion, inactivity due to intercurrent illness or injury, hypo-oxygenation, sleep apnea, deconditioning, and the failure of sprouted, compensatory large motor units. The exercise question in postpolio syndrome is related to the experience of new weakness or loss of muscle function due to overuse, which is often associated with injudicious repeated challenges to weakened musculature. Carefully prescribed exercise can be used for increasing strength and endurance and improving cardiopulmonary conditioning. PMID- 1866951 TI - Rehabilitation of severely injured children. AB - Injury is the leading cause of death and disability in childhood. Ideal systems of care integrate comprehensive management of acutely injured children with rehabilitation. We review the nature of childhood injury, its disabling consequences, and the best ways to manage the care of children with serious injuries. PMID- 1866952 TI - Rehabilitation in cerebral palsy. AB - Cerebral palsy is the most frequent physical disability of childhood onset. Over the past four decades, prevalence has remained remarkably constant at 2 to 3 per 1,000 live births in industrialized countries. In this article I concentrate on the rehabilitation and outcome of patients with cerebral palsy. The epidemiologic, pathogenetic, and diagnostic aspects are highlighted briefly as they pertain to the planning and implementation of the rehabilitation process. PMID- 1866953 TI - Rehabilitating elderly cardiac patients. AB - The aging cardiovascular system undergoes many anatomic and physiologic changes. Increased vascular resistance, myocardial "stiffness," abnormalities of rhythmicity of the sinoatrial node, irregular cardiac rhythms, and alterations in heart rate and blood pressure responses are all seen more frequently in older patients. These changes are likely to impair these patients' ability to make the rapid adjustments necessary to maintain cardiac output during exercise and activity. When cardiovascular disease processes are superimposed on the "normal" concomitants of aging, greater alterations in hemodynamic response to exercise activity are noted than usually occur in younger cardiac patients. Exercise testing of older cardiac patients is safe and is usually needed to prescribe an appropriate intensity of exercise activity. The choice of the exercise protocol, the timing of the exercise test in relation to taking prescribed cardiac medication, the choice of exercise equipment, and special considerations for devices such as pacemakers and automatic implantable cardiodefibrillators must be considered before the exercise test is done. Many of these factors and the presence of either silent or overt cardiac symptoms or untoward hemodynamic events will also affect the exercise prescription. Elderly patients usually show substantial functional improvement when participating in a cardiac rehabilitation program and comply well with prescribed exercise. Early educational intervention may be crucial to reducing disability in these patients. PMID- 1866954 TI - Effect of exercise on muscle function decline with aging. AB - As people age, changes in muscle occur that are associated with a decrease in strength and endurance. These changes result in decreased functional capacity and quality of life. A substantial portion of this decrease is the result not of aging but of the sedentary life-style so frequently associated with aging. In "healthy old" persons and in older animals in experiments, an appropriate exercise program can result in increased strength and endurance. This is true both in longitudinal and short-term studies. As physical impairment increases, the exercise program must be individualized, and results are not as readily predictable. Much work remains before we may be certain how much exercise can be tolerated in these more impaired persons and what the effects may be. PMID- 1866955 TI - Bilateral lower limb amputee rehabilitation. A retrospective review. AB - We retrospectively reviewed 61 cases of bilateral lower limb amputations in patients admitted to a regional amputee rehabilitation program. Of the 61 cases, 41 were analyzed as to functional outcome on discharge, at 1 month, and at 3 months; 20 were not included owing to transfers to acute care or loss to follow up. There were 41 men and 20 women, the average age was 61.5 years, and 47 patients (77%) were discharged to home. There were 25 bilateral below-knee, 14 above-knee and below-knee, 12 bilateral above-knee, 5 below-knee and partial foot, 3 above-knee and partial-foot, and 2 bilateral partial-foot amputations. The average length of stay for all levels was 24.2 days. Most of the patients at the time of discharge achieved a level of limited household walking with the exception of those with bilateral above-knee amputations. A significant improvement in function was noted for all patients at 3-month follow-up, with most patients achieving household ambulation level, but 10 remained independent at wheelchair level for mobility. PMID- 1866956 TI - Stroke rehabilitation: a model predicting return home. AB - We undertook this study to describe the changes in functional status for patients in a rehabilitation program for acute stroke and to identify the variables that best predict discharge home. Of 282 patients, 75% were discharged home. Increases in functional status were found for all 18 activities of the Functional Independence Measure from admission to discharge. Significant predictors of discharge disposition in a logistic regression model were the admission and discharge functional status scores, length of stay, and living arrangement before the stroke. The functional status at discharge was the most important predictor. Knowledge of these predictors can contribute to more appropriate treatment and discharge planning. PMID- 1866957 TI - Reversing disability of irreversible lung disease. AB - Pulmonary rehabilitation is a comprehensive multifaceted team approach for integrating medical management, coping skills, self-management techniques, and exercise reconditioning. It provides patients with chronic lung disease the ability to adapt and live full and nearly normal lives. These changes are possible because the overall disability includes significant reversible components: Patients have bronchospasm, infection, and cor pulmonale; they respond to progressively impaired lungs by progressive inactivity, leading to physical deconditioning. Both factors contribute to dyspnea. Because patients naturally fear dyspnea, they panic easily. During panic, their work of breathing may increase and respiratory failure may result. Pulmonary rehabilitation provides good medical management; provides exercises to increase strength, endurance, and tolerance to dyspnea; and trains patients in panic control. These programs have not been shown to lengthen life span or improve static lung function. They increase exercise performance and render patients functional, independent, and subject to fewer hospital admissions. Pulmonary rehabilitation is the only approach to chronic lung disease short of lung transplantation that improves the long-term outlook for these patients. PMID- 1866958 TI - Exercise testing and training in patients with peripheral vascular disease and lower extremity amputation. AB - Patients with peripheral vascular disease have a high risk of coronary artery disease. The risk is even greater when the peripheral vascular disease leads to lower extremity amputation. Exercise testing using lower extremity exercise has been the "gold standard" for screening for coronary artery disease, but many patients with peripheral vascular disease and those with amputations have difficulty doing this type of exercise. Arm exercise ergometry has been shown to be a safe and effective alternative for the detection of coronary artery disease in patients who cannot do leg exercise. This test has also been used to determine safe exercise levels and may be able to predict the ultimate level of prosthetic use in amputees. Exercise training with arm ergometry also improves cardiovascular efficiency and upper body strength in poorly conditioned patients. Studies are needed to appreciate fully the role of exercise testing and training in the recovery of these patients after amputation. PMID- 1866959 TI - Spinal cord injury. Rehabilitation adds life to years. AB - The National Spinal Cord Injury Statistical Center data base contains information collected prospectively on 13,763 persons injured since 1973 and treated at model systems of care throughout the United States. These data clearly demonstrate improved neurologic status and independent function in activities of daily living following acute care and rehabilitation for most persons with spinal cord injuries. Decreased lengths of initial and subsequent hospital stays and increased survival rates are also documented. Most persons are discharged to a private residence in the community and remain there. Many complete their educations and return to gainful employment after injury. Spinal cord injury has only a short-term effect on marriage and divorce rates, which appears to dissipate within a few years after injury. Overall, these figures demonstrate the dramatic improvements in length and quality of life achieved by most persons with spinal cord injuries during the past two decades. PMID- 1866960 TI - Pregnancy following spinal cord injury. AB - Each year about 2,000 women of childbearing age in the United States have a spinal cord injury. Only a few mostly anecdotal reports describe pregnancy after such an injury. In a retrospective study of 16 women with a spinal cord injury, half of whom have a complete injury and about half quadriplegia, 25 pregnancies occurred, with 21 carried to full term. The women delayed pregnancy an average of 6.5 years after their injury, with an average age at first pregnancy of 26.8 years. Cesarean section was necessary in 4 patients because of inadequate progress of labor. In 5 deliveries an episiotomy and local anesthesia were required, 7 required epidural anesthesia, including all cesarean sections, and 10 did not require anesthesia. Several complications have been identified in the antepartum, intrapartum, and postpartum periods including autonomic hyperreflexia, premature labor, pressure sores, urinary tract infections, abnormal presentation, and failure to progress. Ultrasonography and amniocentesis were used selectively. Women with spinal cord injuries can have healthy children, although there are significant risks and these women have special needs. PMID- 1866961 TI - Walking after spinal cord injury. Goal or wish? AB - Less than a third of patients walk again after a spinal cord injury, whereas every one of them wants to try. Residual function, energy expenditure, the extent of orthotic support needed, and patient motivation will determine the outcome. Functional electrical stimulation and other new orthotic designs have not notably increased the number of persons able to walk after a spinal injury. Rehabilitation professionals can use patient education, illustrating relearning to walk with examples of infants' and toddlers' progress, to assist patients in understanding their abilities and limitations. The final decision on ambulation and orthotic prescriptions can be made in stages after a patient adjusts to a wheelchair-independent level. PMID- 1866962 TI - The strange death of David Rivlin. PMID- 1866965 TI - Taking rehab home. PMID- 1866963 TI - Responding to requests for ventilator removal from patients with quadriplegia. PMID- 1866966 TI - Rehabilitation in the Philippines. AB - The international community has perspective and experience that will freshen our approaches to rehabilitation. Martin Grabois, MD(*), editor of this special section, has gathered articles written by experts from other countries. The intention is to stimulate thought, discussion, and action-and to broaden horizons. PMID- 1866968 TI - Rehabilitation in Mexico. PMID- 1866964 TI - Refusing treatment during rehabilitation. A model for conflict resolution. PMID- 1866967 TI - Rehabilitation in China. PMID- 1866969 TI - Rehabilitation in Great Britain. PMID- 1866971 TI - [Percutaneous drainage of liver and splenic abscess]. AB - 42 patients with solitary (n = 34) and multiple (n = 8) abscesses of the liver (n = 36) and the spleen (n = 6) were treated with ultrasound guided percutaneous interventions. 38 patients (90%) underwent a total of 97 closed abscess aspirations using needles of 0.9 and 1.3 mm in diameter. In 4 cases (10%) percutaneous catheter drainage was performed. Intravenous antibiotics were used in all cases. Those patients with closed abscess aspiration additionally received local injection of aminoglycosides into the cavity. 40 out of the 42 patients could be treated successfully by percutaneous methods for a cure rate of 95.2%. Percutaneous drainage failure occurred in 2.4%. One patient with multiple liver abscesses and catheter drainage died from myocardial infarction (hospital mortality 2.4%). Complications of ultrasound-guided interventions included two minor bleedings, requiring no therapy, and one pleural empyema (complication rate 7.1%). There were no treatment related lethal complications. These results indicate that abscesses of the liver and the spleen up to 10 cm in diameter can be effectively treated by closed (repetitive) needle aspiration and antibiotic therapy with a relatively low rate of complications. About half of our patients with abscesses of more than 10 cm received percutaneous catheter drainage. On the basis of our experience surgical drainage of liver abscesses and splenectomy in splenic abscesses should be restricted to those cases with percutaneous drainage failure. PMID- 1866970 TI - [Ciprofloxacin-omeprazole combination therapy for eradication of Helicobacter pylori]. AB - 20 H. pylori-positive patients with gastric or duodenal ulcer disease (n = 16, one with proof of gastric cancer obtained by histology) or severe non-ulcer dyspepsia (n = 4) were entered in a pilot study to examine the effect of a combination of omeprazole (40 mg) before breakfast and ciprofloxacin (2 x 500 mg) 1 hour after meals for 1 week to treat Helicobacter pylori (Hp). The eradication rate was 15% (3 out of 20 patients) 4 weeks after therapy. Ulcer healing occurred in 2 of 3 patients having eradication and 9 of 11 control patients with positive H. pylori urease test and/or culture 4 weeks after treatment. Despite some good theoretical background, this drug combination is inefficient to eradicate H. pylori and cannot be recommended for routine clinical practice. No major side effects of the therapy-regimen were observed. PMID- 1866972 TI - [Arterial embolization of an arteriovenous fistula with hemobilia after blind liver puncture]. AB - Five days after percutaneous liver biopsy we observed in a 42-year-old man with alcoholic liver cirrhosis severe hemobilia requiring transfusions of packed red cells. By means of super-selective arterial embolization, using gelfoam, the bleeding source, an av-fistula, was successfully occluded. Iatrogenic hemobilia, although seen after percutaneous liver biopsy only in app. 0.005% of the cases, is today the most important cause of biliary bleeding, mainly as a complication (app. 3% of the cases) of the widespread use of interventional procedures of the biliary tree (e.g. PTCD). Therapeutically arterial embolization should be considered first if possible. PMID- 1866973 TI - [Extracorporeal piezoelectric and intracorporeal electrohydraulic lithotripsy in problematic bile duct calculi]. AB - More than 90% of all common bile duct stones are today extracted endoscopically after papillotomy with the Dormia basket in combination with the mechanical lithotripter. For patients with endoscopically unremovable stones, there are now new therapies as an alternative to surgical intervention. Ductal stones can either be fragmented by extracorporeal shock wave lithotripsy or by peroral cholangioscopic guided electrohydraulic lithotripsy. The remaining fragments can then be easily extracted endoscopically. If the stone cannot be removed by using these new techniques, a palliative endoprosthesis can by implanted. We report on our experiences and results with the extracorporeal piezoelectric shock wave lithotripsy and the intracorporeal electrohydraulic therapy in 44 patients with complicated bile duct stones. Applying extracorporeal shock wave therapy, treatment was successful in 75% of the patients with common bile duct stones, intracorporeal electrohydraulic lithotripsy was successful in 71%. By combination of both techniques, the calculi could be removed in 84% of those patients where before one of both therapies had failed. Finally, the rate of success in the above mentioned 44 patients was 93%. It could be shown by this investigation that both therapeutic methods complete each other in the treatment of the complicated common bile duct stones. PMID- 1866974 TI - [Calculating the costs of the most frequent applications of flexible gastroenterologic endoscopy in ambulatory care]. PMID- 1866975 TI - [Peritoneal lavage in acute pancreatitis: the longer, the better?]. PMID- 1866976 TI - [Comment on the contribution: "Effect of omeprazole on serum gastrin levels: influence of age and sex" by Koop et al]. PMID- 1866977 TI - 33rd annual meeting of the Hungarian Society of Gastroenterology. Balatonaliga, 14-18 May 1991. Selected abstracts of lectures and posters. PMID- 1866978 TI - [Characteristics of mathematical interpretation of experimental data during analysis of affinity distribution of serum IgG specific for influenza virus]. AB - The paper depicts the methods of statistic processing of the data and mathematical simulation for the analysis of interactions in the system of antigen antibody. The conditions of various models application are defined. The results of experimental binding curves procession enable obtaining the evidence of affinity-related distribution of serum antibodies which is believed to be an important characteristic feature of their functional activity and to make a quantitative description of maturation of specific immune response. PMID- 1866979 TI - [Immunochemical characteristics of the population structure of antibody-producing cells in experimental influenza]. AB - The authors presented the results of population study of specific IgG-antibody forming cells (AFC) in the pool of mice splenocytes performed in the time-course of simulated influenza with the help of experimental mathematical approach which permitted making a detailed observation of the functional structure of the population and analysing the changes in the spectrum of the AFC subpopulations in the time-course of viral disease. Mathematical simulation of the main stage of immunopointed identification of AFC on +nitrocellulose filters (NCF) permitted the verification of the ratio between the characteristic features of the spots on the NCF and the number and affinity of cell-secreting IgG antibodies. New data are obtained on the formation of the population of +virus-specific IgG-AFC which are featured by discreteness of the AFC +affinity ++ spectrum, cyclic changes in their activity and shifts in the stages of the AFC subpopulation activity. The authors substantiated the necessity to revise the existing theoretical models of the formation of humoral immune response to viral infections. PMID- 1866980 TI - [Humoral cycle as a mechanism providing autoregulation of the processes of the immune system (theoretical model)]. AB - The author presents a hypothesis on a possible mechanism of autoregulation of the immune response maturation in simulated influenza. A theoretical model describing a cyclic process of so-called "humoral cycle" which provides a directed selection of immunocompetent cells' clones and physiologic limitation of cytotoxic reactions. Possible features of humoral cycle function are considered in the concrete experimental examples. The author demonstrated possible mechanisms of immunological barrier violation in synthesis of big amounts of high affinity + antibodies to antigens of causative agent. Possible application of the theoretical model suggested in immunological studies is considered. PMID- 1866982 TI - [Natural killer cells and their protective role in viral infections]. PMID- 1866981 TI - [Formation of target cells in the immunocompetent organ (spleen) of mice with experimental infection caused by influenza A viruses with various properties]. AB - The article presents the data on the time-course of formation of ++virus-pecific target-cells in spleens of mice infected with various types of influenza caused by a virulent viral strain and its avirulent ts-mutation. It was demonstrated that these target-cells occurred in all studied patterns of infection. Their formation turned to be of cyclic character, dose-dependent and closely related with the formation of all known mechanisms of specific and nonspecific cellular defense. The presentation pattern of viral antigens on the surface of these target-cells turned to be variable in the course of the infections evidenced their different recognition in the reactions with the participation of +virus specific antibodies of effectual cells. PMID- 1866983 TI - [General and specific factors of protective reactions in viral infection (facts and hypotheses)]. AB - The authors substantiated the assumptions of virus-induced modification of membranes as the central link in the pathogenesis of viral diseases. The defensive response of the body to viral inoculation was based on the basis of rapid mobilization of all existing factors of nonspecific stability and the following engagement of defense mechanisms which formulated de novo. The results obtained could be a methodological basis for the choice of strategy of viral diseases control. PMID- 1866984 TI - [Changes in the intracellular localization of viral antigens in influenza]. AB - The authors studied intracellular location of the viral structures in the lung tissue in the acute period of infection (on the 3rd-6th after inoculation) and on the 28th day when the infectious virus failed to be detected. It was stated that on the 3rd and 6th day after the inoculation viral antigens were equally distributed between cytoplasmic and membraneous fractions. The 28th day demonstrated the presence of the antigens in cytoplasma and their absence in the cellular membranes of the lung. The results obtained could be used for specification of mechanisms of influenza virus persistence in the body. PMID- 1866986 TI - [The thioldisulfide system as one of the elements of compensatory mechanisms in influenza]. AB - The paper presents the results of a comparative study of changes in a thioldisulfide component of the antioxidation system in cases of sublethal and lethal patterns of influenza. The both patterns were featured with a correlation between individual values of thioldisulfide equilibrium and the severity of virus induced pathological process. Characteristic features of SH/SS coefficient in the lethal pattern of the infection were evidently linked with a specific adaptation of the body under the effect of strong irritants. The possibility to use the parameters of the thioldisulfide system performance for the prognosis of the influenza course was discussed. PMID- 1866985 TI - [Study of biological equilibrium in the body in viral infection of different degree of severity (on the model of influenza)]. AB - The authors made a comparative analysis of the contribution to the outcome of the disease by realization of information of viral genome and host responses in the time-course of simulated lethal and nonlethal mice influenza. They studied the effect of ionol, pathogenetic antioxidant, prevention and depicted absolutely new features of the diseases severity and outlined possible points of effective drug application. The suggested scheme of the time-course measurement of viral involvement of the host body and the formation of its responses could be recommended in the study of mechanisms of the viral infection development and the activity of antiviral agents. PMID- 1866987 TI - [Analysis of interactions between influenza virus and murine serum proteins in non-infected and infected mice]. AB - The presence of proteins in the blood of intact mice of various lines which could form complexes of various stability with influenza virus and have antigen determinants common with mouse IgG was demonstrated. These proteins were different from mouse IgG and their molecular weight was 100-200 and 40-80 kD. The authors described quantitative changes in the studied proteins during simulated influenza as well as under the effect of ionol (antioxidant) administration. The study permitted the assumption that blood serum proteins of intact mice participate in the infection progression and are significant for its prognosis. PMID- 1866988 TI - [Post-stress disorders of resistance of mice to recurrent infection by homologous influenza virus]. AB - A decrease in the mouse resistance to reinfection by influenza virus under the effect of immobilization stress was depicted. Violation in the formation of a long-term resistance to a repeated disease ran in the presence of the high levels of circulating anti-influenza antibodies and not ++always correlated with a post stress impairment of the formation of antigen-reactive clones of cells in the spleen of primarily infected mice. Prophylactic administration of ionol which prevented a post-stress aggravation of the primary influenza infection failed to produce a favourable effect on the immunity in case of reinfection. PMID- 1866989 TI - [Pathogenetic mechanisms of stress-induced aggravation of experimental influenza and its prevention]. AB - It was stated that in stress-induced aggravation of infection realized in transformation of nonlethal patterns of infection into a lethal one there occurred a manifest dysfunction of hypothalamo-hypophyseal-neurosecretory performance (HHNS) featured by a 2-fold decrease in the blood vasopressin and an essential elevation of the hypothalamic one. The phenomenon is being suggestive of a possible blockage in the hormonal discharge into circulation and the limitation of its participation in the development of defensive and compensatory reactions. Identical HHNS dysfunction was noted in the lethal pattern of the infection. The authors formulated the concept of the main pathogenetic points underlying the damage of vegetative regulation centres. Mechanisms of viral and tissue metabolic damage of CNS were revealed. The authors substantiated the advisability and prospective use+ of antioxidants as applied to the prevention of severe course of influenza and its complications in extremely aggravated patterns. PMID- 1866990 TI - [The role of lipid peroxidation in post-stress aggravation of influenza and the corrective effect od ionol]. AB - Activation of lipid peroxidation in the tissues of the lungs, brain and liver which was followed by a compensatory increment in the activity of antioxidative enzymes was demonstrated in experimental mice with isolated or combined effect of immobilizing stress or influenza infection. The usage of antioxidative drug, ionol, decreased the levels of lipid peroxidation, alleviated the aggravated course of the infection which occurred after the preliminary immobilization. The authors substantiated the role of activation of lipid peroxidation as a significant link in the disease progression in case of isolated or combined effect of stress or infection and considered the prospective ways of chemotherapeutic management of viral infections. PMID- 1866991 TI - [Use of various bibliometric methods in operative evaluation of research activities of the research institutions of medico- biological profile]. AB - Based on the analysis of the indices accepted for the evaluation of scientific work in research institutes, a suggestion was proposed that the putative instead of realized value of the scientific product should be evaluated. This implies employment of such bibliometric techniques of analysis of the volume and quality of the used information as: total number of references in scientific works, reference to the most recent publications and foreign sources, and the interdisciplinary index rated according to the subject-relation of the cited works. Studies of selected indices based on the analysis of one-year scientific journal publications and of manuscripts sent for print, as well as of reports made by the Kiev Research Institute of Otorhinolaryngology of UkrSSR Ministry of Health and by the Research Institute of Hematology of BSSR Ministry of Health, paralleled with a comprehensive consideration of the reference peculiarities and expert evaluation of the scientific material proper, allowed for making a conclusion on the importance of the role played by the bibliometric data in making the expert formal and objective and in operative evaluation of the activity of scientific communities and/or trends. This is of special significance for information and scientific policy making. Such investigations may be carried out by expert information workers. PMID- 1866992 TI - [Functional activity of antibody-producing cells in mice with experimental influenza]. AB - The paper presents the findings on the functional activity of specific antibody forming cells (AFC) in the time-course of the primary influenza infection in mice. The concept of AFC functional activity is validated. Studying of the AFC population in the pool of splenocytes based on the analysis of functional activity permitted one to make a detailed description of specific AFC, and make a series of conclusions of the technique of AFC identification, reveal the changes in the structure of the virus-specific AFC population under the influenza infection which are not related to their quantity. Principle difference was revealed in the time-course of AFC functional activity in various patterns of influenza. Continuous changes in the AFC structure were observed during the whole period of observation. PMID- 1866993 TI - [The contribution of genetic factors to perinatal pathology and infant mortality]. AB - The authors consider the contribution made by genetic factors to perinatal and infant mortality on the basis of many-year studies performed in the Minsk Teratology Center and analysis of the data available in the literature. In 1972 1984 there was an increase in the incidence of congenital malformations among deceased children. Genetic factors predispose to at least 7-8% postimplantation embryonal and fetal elimination. Perinatal and neonatal mortality is caused by congenital malformations in 19.1 and 37% of cases, respectively. A genetic analysis has indicated that 23.2% of them are induced by genic, chromosomal, and genomic mutations and 51.0% are caused multifactorially. The prevention of genetically determined perinatal mortality is most effective in implementing the screening programs for detection of heterozygous carriage along with subsequent prospective examination and prenatal diagnosis. PMID- 1866994 TI - [A program to lower perinatal morbidity and mortality in women with multiple pregnancies]. AB - A total of 511 females with multiple pregnancy (486 with twins and 25 with triplets) were examined for the nature of fetal development, and management of pregnancy, labor and postpartum period. An early diagnosis was found to play a decisive role in the implementation of therapeutical and preventive measures. A classification of the prenatal development of monozygotic twins was presented. It was shown that the optimal management of pregnancy in multiple-pregnant females was effective in relation to the time of employing the basic components of the program. It was demonstrated that the active management of labour was important in multiple pregnancy; the results of clinical trials of this procedure were also provided. In terms of the risk for perinatal morbidity and mortality, three groups were identified, these may include females with multiple pregnancy. Implementing the proposed treatment-and-prevention measures showed that perinatal morbidity and mortality rates in multiple pregnancy might be substantially reduced. PMID- 1866996 TI - [Pathology of the spiral arteries of the uterus and its significance in the pathogenesis of disorders of the uteroplacental circulation]. AB - The literature survey concerning the morphological aspects in the uteroplacental blood flow is presented. The methodological approaches applied in the investigation of spiral arteries are classified. Changes in uterine structures in normal pregnancy are characterized. A great emphasis is laid on gestational alterations in spiral arteries. The types of pathological processes occurring in the spiral arteries are described. The data available in the literature are given on the incidence of various types of pathology and its association with nephropathy, intrauterine fetal hypertrophy, and other abnormalities. PMID- 1866995 TI - [The immune system of the human fetus in the perinatal period of development in maternal health and disease]. PMID- 1866997 TI - [Possibilities of the prenatal diagnosis of congenital developmental disorders in the second trimester of pregnancy using ultrasound]. AB - Ultrasonography was used in the second pregnancy trimester as a noninvasive method of prenatal diagnosis of congenital malformations (CM) in 1071 pregnant women. These were found in 1.2% of the examinees, were local and multiple with predominance of CNS anomalies. Key ultrasonic signs of CM are specified. It was noted that a fertilized egg presents valuable specific and nonspecific information. Ultrasonography is shown to be of high informative value in prenatal diagnosis of CM in the second trimester. PMID- 1866998 TI - [Current problems of ante- and perinatal pathology]. AB - The paper provides strong evidence for further postmortem investigations in the ante- and perinatal periods, in the combination of those of the afterbirth. The very early antenatal abnormalities (gametopathy and blastopathy) have been less studied. There are predominant congenital malformations of the organs concurrent with placental incompetence among embryopathies. In the fetal period, the authors identify an abnormality in the early fetal phase when placental insufficiency, fetal hypoxia and intrauterine death prevail; that in the mid fetal phase concomitant with infectious fetal injuries and acute and chronic placental failures due to maternal diseases; and that in the late fetal phase that covers perinatal death. The time course of reasons for stillbirth and neonatal death was analyzed in Moscow in 1986-1989. Etiological causes of early and late abortions have been identified, which is a real reserve of reduction in ante- and perinatal mortality rates in this country. PMID- 1867000 TI - [Birth trauma as a problem of obstetrics, pediatrics and pathological anatomy]. AB - Birth injury as a nosological entity involves 2 groups of pathological processes: 1) traumatic injuries and 2) dyscirculatory disorders. Either bleeding cannot be classified as cranial injury without specifying its genesis and in the absence of traumatic injuries. Brain compression is one of the traumatic injuries, underestimation of its signs leads to the hyperdiagnosis of fetal asphyxia. The correlations found between the arrangement of periosteal congestion and tentorial injuries and the pattern of calvarial osteectopy help clarify the pathogenesis of a birth injury, but taking into account the biomechanics of labour, which is essential for obstetricians and pathologists. PMID- 1866999 TI - [Means of lowering the perinatal mortality in pregnant women with diabetes mellitus]. AB - The paper gives some current approaches to the management of pregnant women with diabetes mellitus, in terms of perinatal medicine. These are based on a comprehensive detailed clinical examination of 104 patients, which involves the hormonal fetoplacental complex function, hypophyseo-thyroidal system, hemocoagulation system by using ultrasonic tools (fetal biometry and echocardiography, Doppler echometric studies of the fetoplacental blood flow in the umbilical vein, umbilical artery, and fetal aorta). A differential approach was proposed to the management of pregnancy and delivery of patients with diabetes mellitus, which allows perinatal mortality to be reduced. PMID- 1867001 TI - [Reserves for lowering the neonatal mortality of premature children]. AB - A tendency for a decrease in the rate of neonatal mortality among preterm babies could be followed up in industrialized countries for the current decade. This tendency is less pronounced in the USSR. Therefore newer diagnostic and therapeutic approaches developed in the clinical department of the Scientific and Research Institute of Pediatrics, the USSR Academy of Medical Sciences, could be regarded as reserves for the reduction of neonatal mortality in preterm children. They include the analysis of etiological structure of present-day pyo-septic diseases (monitoring of intrahospital flora, target-oriented treatment-the use of anti-klebsiella plasma); consideration of new aspects of pathogenesis (population structure and the receptor function of the blood defensive cells); metabolite therapy; individualization of antibacterial treatment on the basis of pharmacokinetic assessment; optimized breeding techniques (prolonged probe nutrition); background correction (perinatal encephalopathy, the syndrome of respiratory distress); newer socio-medical approaches (psychotherapy of nursing mothers, "kangaroo" method). PMID- 1867002 TI - [Scientific and practical tasks of medical embryology in the prevention of perinatal pathology]. AB - The paper analyzes the clinical aspects of medical embryology, emphasizes the topical problems of progenesis, fertilization, cleavage, gastrulation, implantation, and histo-, organo-, and systemogenesis. The current status of the studies into the mother-fetus system is explored. The new organizational patterns of the connection between theory and practice, which enables medical embryology to substantially affect the health care system are also discussed. PMID- 1867003 TI - [Homeopathy as a therapeutic system]. AB - A brief account of the major homeopathic principles making up a therapeutic system is presented. The opinions of different authors on the methodology of research into the area of homeopathy are also discussed. In addition, recommendations on the clinical trials of homeopathic methodologies are offered. PMID- 1867004 TI - [Scientific prediction in the management system of gerontological studies in the USSR]. AB - The paper characterizes the current status of gerontological studies in the USSR, defines the directions in which the USSR is in the lead or behind other foreign countries, provides long-term predictions for developing the studies in gerontology in this country, outlines the measures needed for their implementation, and emphasizes the significance of the goal-oriented financing of priority research developments. PMID- 1867005 TI - [The role of viral agents in the induction of atherosclerosis from the point of view of the etiopathogenetic aspects of slow infections and the association of atherosclerosis with viruses]. PMID- 1867006 TI - [Ways of reducing perinatal morbidity and mortality due to hereditary pathology]. AB - The paper presents different ways of preventing the perinatal morbidity and mortality due to genetically predisposed abnormalities, such as environmental protection; definition of the factors having a mutagenic influence on the female; family planning, medico-genetic advisory. It also outlines the methods of perinatal diagnosis, which is now the most effective tool for birth prophylaxis of a baby with a hereditary abnormality. PMID- 1867007 TI - Correlation of amino acid residues in the M1 and M2 proteins of influenza virus with high yielding properties. AB - The ability of influenza A viruses to replicate to high titer in the allantoic sac of the chicken embryo has been mapped to the matrix protein gene (RNA 7). Because influenza A/WSN/33 (H1N1) virus grows poorly in this host but contains a matrix protein gene with a sequence similar to sequences from viruses that grow well in eggs, we derived a single gene reassortant containing only the M gene from A/WSN/33 (H1N1) in a background of the other 7 RNA segments from A/Philippines/2/82 (H3N2) (a low yielding virus, hy-). This reassortant replicated 10 times better than the A/WSN parent itself, indicating that the high yielding (hy+) phenotype of the A/WSN/33 M gene may be suppressed by one of the other genes of A/WSN/33. Comparison of M gene sequences between hy+ (including A/WSN/33) and hy- strains allowed us to correlate specific amino acid positions in M1 and M2 proteins with the growth properties of influenza viruses. PMID- 1867008 TI - Heterogeneous forms of polymerase proteins exist in influenza A virus-infected cells. AB - In influenza virus-infected cells a virus coded polymerase that consists of three polypeptide subunits, namely PB1, PB2 and PA, mediates both transcription and replication. Radioimmunoprecipitation with monospecific antisera to each of the polymerase proteins revealed additional forms of PB1 and PA proteins in infected cells. PA antiserum detected two additional proteins of 62k and 60k and PB1 antiserum recognized two additional proteins of 85k and 70k. Further investigation was carried out on the 62k PA and 85k PB1 related proteins. Limited proteolysis peptide mapping showed that these proteins are subsets of their normal counter-parts. These new forms of polymerase proteins are designated as "b" forms (PAb and PB1b) to distinguish them from the previously recognized forms designated as "a" forms (PAa and PB1a). Both PAb and PB1b proteins were found in cells infected with all the influenza type A viruses tested indicating that they are evolutionarily conserved. Pulse chase experiments showed that the "b" forms are not derived from "a" forms. This suggested that "b" forms are translated independently. The "b" forms were not detected in purified virus but were found to be associated with intracellular RNP templates, suggesting a role for these proteins in intracellular virus replication events. PMID- 1867010 TI - Construction and characterization of expression systems for the env gene of ts1, a mutant of Moloney murine leukemia virus-TB. AB - A temperature-sensitive mutant of the Moloney murine leukemia virus-TB, ts1, causes hindlimb paralysis and immunodeficiency in mice. At the restrictive temperature, the envelope precursor polyprotein, gPr80env, is inefficiently processed intracellularly, and this is associated with the neurovirulence of ts1. To test the hypothesis that expression of the envelope proteins of ts1 alone without infectious virus production can induce paralysis, it is necessary to use either transmissible retroviral expression vectors or microinjection of eukaryotic gene expression plasmid to introduce the env gene of ts1 into germlines of mice. In this study, we have constructed three retrovirus vectors and three gene expression plasmids, all of which contain the env gene of ts1. By comparing the different expression systems, we found that one construct, pts1 env(F) can express the envelope proteins at a level comparable to the level expressed in ts1-infected cells. Furthermore, the expressed envelope proteins of pts1-env(F)-transfected cells possess the phenotypes of the proteins expressed by the env gene of ts1. PMID- 1867009 TI - Molecular characterization of the M genomic segment of the Seoul 80-39 virus; nucleotide and amino acid sequence comparisons with other hantaviruses reveal the evolutionary pathway. AB - The genomic M segment of Seoul 80-39 virus was characterized by cloning and nucleotide sequence analysis. The virion M RNA segment is 3651 nucleotides long with the 3' and 5' terminal sequences inversely complementary for 20 bases. A single open reading frame was detected in the viral complementary-sense RNA which can encode a polypeptide of 1133 amino acids. The Seoul 80-39 virus M segment was compared with the M segments of related viruses, Hantaan 76-118, Hallnas B1 and Sapporo Rat (SR-11) virus. Our results demonstrate a significant similarity between M RNA segments of the Seoul 80-39, Hantaan 76-118, Hallnas B1 and SR-11 viruses. The degree of conservation of both nucleic acid and protein sequences between these viruses reveals a close evolutionary relationship. Furthermore, it is evident that the serotypic profile of hantaviruses is determined by the rodent host species from which the virus was isolated and not by the geographical area. PMID- 1867011 TI - Cancer mortality in Switzerland, 1985-89. PMID- 1867013 TI - [Socially selective degree of achievement in community-oriented intervention- analysis of participation in health actions of the German Cardiovascular Prevention Study]. AB - The subject of this article is an analysis of participation in campaigns of the German Cardio-Vascular-Prevention Study (GCP). In 1988 two representative surveys were carried out in the City of Bremen. Altogether, 2360 persons were questioned. Of these, 149 stated that they had participated in campaigns of the GCP. A multivariate analysis shows that the probability of participation was highest for people with an interest in health-related issues and for members of higher social classes. The discussion of these result emphasizes some problem areas in the use of such community-based intervention concepts. PMID- 1867012 TI - [Air pollutant burden and bronchial asthma in school children]. AB - To examine the possibility of an effect of indoor and outdoor exposures on the prevalence of asthma in childhood we conducted a cross-sectional study in the area of Freiburg city and two communities in the Black Forest. The study group consists of 704 children aged 7 to 16 years. The children and their mothers took part in a standardized interview and a medical examination. Indoor exposures were assessed from information gathered in the interview by two different indices: (a) heating system and single room heating, and (b) the amount of indoor ventilation. The measurement of outdoor pollutants took into account weekly estimations of NO2 and combustion particles. The presence of asthma was recorded according to a previous medical diagnosis. Confounders were assessed during the interview (passive smoking, genetic predisposition to asthma etc.) or during the medical examination (cutaneous sensitization with a skin prick test). For the analysis of the data we applied logistic regression models and estimated odds-ratios. Only one of the four hypothesis variables displays a significant effect on the prevalence of asthma: Stoves as heating device carry a 4.8-fold relative risk for asthma compared to other types of heating. Among the confounding variables controlled for in the explanatory model, cutaneous reactions showed a relative risk of eight. PMID- 1867014 TI - [Education level and participation in early cancer diagnostic studies in the Federal Republic of Germany]. AB - In Germany only a few persons take part in cancer screening programs. In order to raise participation rates one needs to ask which subgroups of the population these efforts should focus on. Studies from other countries unanimously show that participation rates decrease with decreasing education and income. Based on this results it was hypothesized that in Germany participation rates also decrease with decreasing education. In a secondary analysis of data from a population survey conducted in Germany in 1987, the hypothesis could be supported only for employed women, whereas for men a non-significant and for not employed women a significant, association was found in the opposite direction. PMID- 1867015 TI - [Do cancer patients survive longer today than before? Survival analysis of cancer patients in the Saar region from 1972 to 1986]. AB - In the Saarland there is a population-based cancer registry, which has collected information about cancer cases over a long period. An important task of population-based cancer registries is the analysis of its data in respect to incidence, mortality and survival of cancer patients. Not all patients who have been diagnosed with cancer die of that disease. In order to evaluate the survival of cancer patients in respect of their particular disease, survival rates are calculated after the determination of the influence of other causes of death. The so-called relative survival rates (calculated for the first five years after diagnosis) are also used in order to evaluate simultaneously the prognostic importance of variables such as sex, age and year of diagnosis. This analysis with data from the cancer registry of the Saarland deals with 9 tumor localizations: stomach, colon, rectum; breast, cervix uteri and corpus uteri; prostate, lung, malignant skin melanoma. In general the 5-year relative survival rates slightly increased when the time period 1972-1976 was compared with 1982 1986. Cancer of the corpus uteri was one exception, in that the relative survival rate was constant over time, and cancer of the cervix uteri was another, in that a decrease of relative survival rate was found, which together with the decreasing incidence might be ascribed to a successful early detection program. There was no significant improvement in the relative survival time for lung or breast cancer patients. PMID- 1867016 TI - [Myocardial infarct and occupational reintegration in insured patients of a regional sickness fund]. AB - For a region in the Federal Republic of Germany, some important indicators for procedures and outcomes of the care of myocardial infarction patients have been demonstrated. The study was restricted to patients under 65 years of age and was based on routine data from the health insurance fund. Length of stay in the hospital was more than five weeks. Half of the patients who underwent coronary angiography coronary bypass surgery had to wait longer than three or five months, respectively, for the procedure. Half of the patients who were treated in a rehabilitation clinic had to wait more than two weeks elapsed after discharge from the acute care hospital. Utilization of this type of service was about 75% for patients who were employed before the infarction compared to only about 15% for patients who had already been retired from work. Only about half of the men under 60 years returned to work after their infarction. Half of the patients were still disabled after nine months after onset of disease. The study was part of a project for the development of care for patients with myocardial infarction in that region. It turned out that routine data are effective for the description of the situation. Studies of this type can be repeated in other regions with comparable little effort. PMID- 1867017 TI - [Intra-operative complications in arthroscopic operations. Results of a re arthroscopy study]. AB - The overall complication rate of arthroscopy and arthroscopic procedure is very low. Iatrogenic arthroscopic joint lesions, especially the alteration of articular cartilage does occur, but there is no idea of proportions and importance of these lesions. Persistent pain and swelling after arthroscopic procedure lead to repeat arthroscopy and therefore to a check of diagnosis and treatment. From 1. 1. 1987-30. 6. 1990 we carried out 239 second-look arthroscopies of knee joint, 121 after diagnostic arthroscopy and arthroscopic procedure. In 34% we had to revise the first diagnosis. After arthroscopic procedure we saw in more than 50% unsatisfactory results. The most important reason for persistent symptoms after arthroscopic meniscectomy were cartilage lesions. PMID- 1867018 TI - [Surgical therapy of medial femoral neck fracture]. AB - During 1986 to 1988 64 patients with the diagnosis acute medial hip fracture have been operated in the University Hospital (Charite) by hip endoprosthesis. Patients up to the age of 75 years have been treated by total hip endoprosthesis. Patients older than 75 years got a femoral head prosthesis. In 92.3% of the patients with femoral head prosthesis no complications were observed. In our hospital we prefer the implantation of the femoral head prosthesis in patients older than 75 years. PMID- 1867019 TI - [Management of femoral neck fracture with an intermediate (dual head) prosthesis in geriatric surgery]. AB - Between 1980 and 1989 in 195 elderly patients with fractures of the femoral neck a duo-cup endoprosthesis was inserted. The average age was 78 years, most of them were high risk patients with sometimes more than 2 preexisting diseases. The hospital mortality after hip replacement was 9.7%, specific complications like protrusio acetabuli and shaft fractures were not observed. In 2 cases immediate postoperative luxation required reintervention. The incidence of infection was significantly reduced to 2.4% after antibiotic therapy. When discharged from hospital, 86% had a good functional result. We regard hemiarthroplasty with duo cup endoprosthesis as an acceptable alternative to total hip replacement in elderly patients with fractures of the femoral neck. PMID- 1867020 TI - [Monteggia injuries. Therapy and late results in 204 cases]. AB - A follow-up check of 204 Monteggia fracture-dislocation in two clinics showed that in 84% of the cases an operative treatment led to good functional late results. In 65% of the patients treated conservatively, the mobility of the elbow was evidently limited. Plate fixation has been proved to stabilize ulna fractures, a suture of the anular ligament was in the majority of cases not required. PMID- 1867021 TI - [Functional conservative treatment of humerus shaft fracture with the plaster brace]. AB - The functional-conservative treatment of fractures of the humerus shaft is the most efficient method today. It is an uncomplicated and reliable method for outpatient therapy. In our opinion only second degree open fractures and vessel injuries are a contraindication. A few guidelines taken into consideration enable everybody to learn the handling of plaster brace in a short time period. All fractures we treated in this way showed an osseous fracture healing. PMID- 1867022 TI - ["Ledderhose" disease. Plantar fibromatosis--clinical aspects]. AB - The Ledderhose's diseases is a relatively rare and not well known clinical picture. Even there are tight pathomorphological and clinical relations to the Dupuytren's contracture, the genesis is also here quite unknown. Because of inefficiency of conventional therapy the surgical treatment is the only alternative. On the sample of 12 operations in 7 patients from 1979 to 1989 surgical procedure and long-term results are discussed. PMID- 1867023 TI - [Evaluation and objective assessment of the treatment course of burn injured children]. AB - Between 1984 and 1989 70 out of 76 children, who underwent a primary inpatient treatment for thermal injury, had predominant second degree burns affecting 3 to 25% of body surface. Data of them, concerning epidemiology, first aid, run of inpatient and following outpatient therapy, were documented and summarised. All patients were physical examined and we judged functional and cosmetic results at least half a year after the injury. A uniform score allowed us a comparison of two different concepts of local therapy: closed treatment with impregnated gauze dressings vs. application of ointment (Flammacerium). Kind of documentation and score are proved to be of advantage in estimating run and results of treatment. PMID- 1867024 TI - [Intra-tendinous ganglion]. PMID- 1867025 TI - [The ultrastructure of plasmid-containing and plasmid-free Salmonella derby cells]. AB - The comparative electron-microscopic study of S. derby plasmid-containing and plasmid-free cells has revealed certain differences in their structures: These structural differences are always accompanied by changes in the form and size of the cells, the form of the cell wall with the appearance of fimbria-like processes, depending on the presence or absence of S. derby R-plasmid in the cells. These differences in the morphology and ultrastructure of S. derby cells, associated with the R-plasmid, are of interest in the study of molecular mechanisms of plasmid action on the development of various forms of whole cells and individual bacterial structures, which play an important role in the cell function. PMID- 1867026 TI - [The isolation of Vibrio fluvialis on the territory of the USSR]. AB - For the first time V. fluvialis strains were detected on the territory of the USSR. The taxonomic position of these vibrios was determined by their nucleotide DNA composition (the content of guanine + cytosine was 49.3-51.0 mole%) and the characteristic features of their phenotype. The individual features of the strains consisted in their capacity for agglutination with cholera antisera, groups 01 and Inaba, in diagnostic dilutions in the presence of differences in genomes and phenotypes with cholera vibrios. Molecular hybridization DNA-DNA also gave no confirmation of their relationship to cholera vibrios (23-26% homology). The comparative study of V. fluvialis strains from the USSR and other countries by a broader set of their phenotypical signs confirmed their identity. PMID- 1867027 TI - [Cellular immunity function in HIV-1-infected persons]. AB - The data on the state of cell-mediated immunity in patients with AIDS-related complex are presented. The synthetic peptide of membrane protein gp120 of HIV-1 was shown to inhibit leukocyte adhesion in persons under examination, as well as to have the tendency towards inhibiting the chemotaxis of migratory cells. The maximum effect was achieved at a peptide concentration of 10(-6) M. The data obtained in this investigation suggest the presence of specific cell-mediated sensitization to the fragment of protein gp120, detected by the adhesion inhibition test with the use of spectrophotometric techniques and the capillary evaluation of the chemotaxis of migrating cells, in patients with AIDS-related complex. PMID- 1867028 TI - [Inhibitor factors in the serum of patients with the AIDS-related complex]. AB - The data on the presence of factors blocking the reaction of E-rosette formation and leukocyte chemotaxis in the blood sera of patients with AIDS-related complex (ARC) and HIV-positive donors are presented. Most frequently the blocking of E rosette formation coincided with the presence of a inhibiting effect on the migration capacity of leukocytes. This blocking activity was not linked with the presence of C-reactive protein in the circulation stream. The treatment of ARC patients with plasmapheresis and/or travolol was accompanied either by the disappearance of blocking activity or by the appearance of activity stimulating E rosette formation. PMID- 1867029 TI - [A mathematical simulation model of the AIDS pandemic]. AB - In this work the mathematical model of the spread of AIDS pandemic over 5 regions of the world are presented. With the values of all parameters corresponding to the initial dynamics of the process the prognosis obtained with the use of this model is highly unfavorable. The program of mathematical modeling, developed in this investigation, may help in the evaluation of the effectiveness of different measures aimed at the liquidation of the epidemic process and in their correction, as well as in the choice of the optimum strategy of AIDS control. PMID- 1867030 TI - [Experience with the selective decontamination of the intestines]. PMID- 1867031 TI - [The use of immunoenzyme analysis and the vibriocidal antibody reaction in the serological examination of persons who have had cholera and of those in contact with them]. AB - The preparation of cholera toxin obtained from Vibrio cholerae strain 1310 has been used for producing solid-phase immunosorbent intended for the enzyme immunoassay (EIA). The use of EIA and the vibriocidal antibody test (VAT) in the serological study of former cholera patients and persons having contacts with them has made it possible to show the excess of the antitoxic activity of sera over their vibriocidal activity in all subjects covered by the dynamic study (from 5-14 days to 8-10 months). EIA and VAT can be used as auxiliary methods in epidemiological survey and analysis. PMID- 1867032 TI - [The determination of the dates of seasonal upsurges in morbidity by a computational method]. PMID- 1867033 TI - [The modification of the cell wall proteins in group A streptococci type M 29 under the influence of spermidine contained in the culture medium]. AB - The addition of spermidine into growth medium used for the cultivation of group A streptococci, type M 29, leads to changes in the amino acid composition of cell walls and surface proteins isolated by the method of E. H. Beachey et al. The separation of surface proteins into fibrinogen-binding proteins and fibrinogen receptors by affinity chromatography techniques on cellulose with covalently bound fibrinogen indicates that the proportion of these proteins in pepsin extracts obtained from different strains varies. Both spermidine and avirulent strains have similar content of fibrinogen-binding proteins, although these proteins are absent in virulent strains. Different amounts of fibrinogen receptors are extracted from all strains. As shown in the enzyme immunoassay, fibrinogen receptors contain no group-specific polysaccharide A, Fc-receptors and interact with total antiserum to group A streptococci, type M 29 [correction of 28]. Fibrinogen receptors isolated from the strains under study have been found to have similar amino acid composition. On the basis of these results we believe that neither receptor capacity to fibrinogen nor amino acid composition is indicative of the protective properties of protein M. PMID- 1867035 TI - [The isolation of tetanolysin and study of its protective activity]. PMID- 1867034 TI - [The cytochemical marking of lymphocyte subpopulations in determining the immunoreactivity status of children vaccinated with a live measles vaccine]. AB - In 54 children aged 1.5-2 years, immunized with the same batch of live measles vaccine prepared from strain, the relative and absolute numbers of different lymphocyte subpopulations were determined in parallel by means of two cytochemical reactions: for acid alpha-naphthyl acetate esterase and acid phosphatase in their dynamics. According to the data obtained in these reactions, the determination of lymphocyte subpopulations by two cytochemical methods in the same blood sample yielded similar results indicating that immunization with attenuated measles virus strain induced a rise in the number or zero lymphocytes and was accompanied by the decrease of the immunoregulatory index (T-helper/T suppressor ratio), most pronounced in children with a high level of antibody formation. PMID- 1867036 TI - [An immunoenzyme method for demonstrating Coxiella burnetii antigens]. AB - Materials on the development of an enzyme immunoassay (EIA) system for the detection of the antigens of C. burnetii, the causative agent of Q rickettsiosis, are presented. The system is highly specific and effective with respect to both corpuscular antigens of phases 1 and 2 and soluble antigen (lipopolysaccharide). The sensitivity of this method varies within the range 5-100 ng/ml. The effectiveness of EIA as a quantitative (semiquantitative) control test used in the process of the production of Coxiella preparations has been demonstrated. PMID- 1867037 TI - [The effect of cytostatics and corticosteroids on the phagocytic and fungicidal activity of the neutrophilic granulocytes]. AB - In vitro tests have revealed that cytostatic agents and corticosteroids, introduced in vivo, produce an inhibitory effect on the phagocytic activity of mouse neutrophil granulocytes and on their capacity for the destruction of Candida albicans blastospores. The action of the above-mentioned preparations may be an important pathogenetic factor which when introduced into the animals, contributes to the development of candidiasis. PMID- 1867038 TI - [The ultrastructure of the interaction of Rickettsia sibirica and R. slovaca with the cells of ixodid ticks]. AB - The ultrastructural aspects of the interaction of R. sibirica and R. slovaca with cells of mites of the species Dermacentor reticulatus, D. marginatus and Ixodes ricinus after their parenteral infection, as well as in the organs of D. marginatus infected naturally in the environment, have been studied. Both rickettsial species have similar morphology in different organs of the vector. These rickettsiae not only multiply, their populations are also partly destroyed in phagolysosomes. The natural mixed infection of R. sibirica and orbivirus in cells of D. reticulatus is described. As shown in this study, both associates pass through the complete ontogenetic cycle of development on the level of the host body and also on the level of an individual cell. PMID- 1867039 TI - [Contacts between the cells in bacterial colonies]. AB - The interaction of cells in microbial colonies has been studied by electron microscopic techniques. Two types of contacts between cells have been found to exist in the colonies of Gram-negative bacteria of the genera Escherichia, Shigella and Salmonella: close cell adhesion due to the fusion of cell-wall outer membranes and the formation of intersections consisting of membranous tubules. At the sites of close adhesion the fusion of cytoplasmic and outer membranes have been found to occur in Bayer's zones. In the colonies of Gram-positive bacteria of the genera Staphylococcus and Brevibacterium only one type of contacts has been revealed: the fusion of the peptidoglycan layers of the cell walls. The results of this study indicate that in colonies bacteria are not completely isolated; their interaction leads to the formation of a three-dimensional structure denoted as a cooperative cell system. PMID- 1867041 TI - [The modern interpretation of the basic categories of epidemiology]. PMID- 1867040 TI - [The absence of differences between El Tor cholera and classical cholera]. PMID- 1867042 TI - [Vaccines in the public health of the USSR. Their general characteristics]. PMID- 1867043 TI - [The differentiation of intestinal Escherichia coli infections]. PMID- 1867044 TI - [The humoral immune response of different strains of mice after intragastrointestinal immunization with human sperm antigens]. AB - The inbred Balb/c and C57 mice, and the outbred Swiss Webster mice were intragastrointestinally immunized with human sperm antigens. The lymphocytes from the spleen, mesenteric lymph node (MLN), Peyer's patch (PP) and uterus or epididymis were isolated and cultured. The lymphocyte-secreting antisperm IgG and IgA and the antisperm antibodies in the gut wash and serum were determined with enzyme-linked immunosorbent assay (ELISA). In the Balb/c and Swiss Webster mice, the immune responses to sperm have shown to be stronger than that in C57, stronger in female than in male. The antigenicity of sperm membrane extracts seems to be higher than that of whole sperm. Antisperm antibodies secreted by lymphocytes from the epididymis and uterus have demonstrated to be detectable. For stimulation of the local immune response, the intra-PP and intralumina immunizations are more effective than others. PMID- 1867045 TI - [The in vitro induction of antibody responses of human lymphocytes and its application to hybridoma production]. AB - Sources of immunized lymphocytes constitute one of the main obstacles in the production of human monoclonal antibodies. We tried to get them through in vitro immunization. Cells from excised tonsils or trauma spleens were used for the induction of antibody responses in vitro. Antibodies to different antigens including sheep red blood cells, ovalbumin, tetanus toxoid, and hepatitis B surface antigens were induced in 7-14 days' cultures. Taking tetanus toxoid as antigen, we analysed the various factors required for antibody induction with statistics analysis, which included cell separation method, T cell conditioned medium, antigen dosage, serum content, and concentration of mitogen PWM and LPS. The results showed: (1) The cell separation method influenced the antibody production significantly in comparison with other factors. It signified that immune cells' combination was the most influential factor. (2) Serum also constituted quite important influencing factor especially in the later period of culture. However, it did not make much differences if it attended 10% or so. The antigens and mitogens tended to be used at low concentration. (3) Due to the significant variation among individuals and among different antigens, it is suggested to set up the culture system with some flexibility so as to adapt to the variation in cells and antigens from different sources. The present culture system we use includes nylon wall column separation of cells, suitable range of antigens (three doses instead of one), and either 10% T cell conditioned medium or a mixture of 1 microgram PWM/ ml + 0.1 microgram LPS/ml. The human B lymphocytes stimulated in vitro with tetanus toxoid were used for the construction of human hybridomas. PMID- 1867046 TI - [The effect of hypocrellin A on the lipid bilayer of erythrocyte membrane]. AB - In this paper, using human erythrocyte membrane, the effect of Hypocrellin A on the lipid bilayer of the membrane was studied by measuring the change of the fluidity of the membrane, the energy transfer of the fluorescent probes, the shift of the fluorescent emission peaks, and the split of band-a of Hypocrellin A. The results showed that in the presence of HA, the fluidity of erythrocyte membrane was increased, the fluorescence intensity of the probes was decreased, and the fluorescence peaks shifted blue. These phenomena took place more seriously with the increment of HA concentration. Meanwhile, the band-a of HA excitation spectra was splitted. It was suggested from all of the results that HA could significantly perturb the lipid bilayer of erythrocyte membrane, there were interactions existing between the Hypocrellin A and the membrane. The HA was mainly located in the middle range of the membrane lipid bilayer when in high concentration (mainly to the 12-16 positions of the long chain fatty acid). PMID- 1867047 TI - [A distinct centro-peripheral gradient of development in dopaminergic amacrine cells of cat retina]. AB - The centro-peripheral gradient of development in dopaminergic (DA) amacrine cells of cat retina has been studied by TH immunocytochemical method. Type I of TH immunoreactive neurons is typical DA cell. They reveal a clear centro-peripheral gradient of differentiation and maturation in space and time course during postnatal development. (1) At P1 stage, the TH I cells vary in TH immunoreactivity, soma sizes and dendritic maturation. Responding to degree of development, they can be divided into I1, I2 and I3. The more differentiated I1 cells, larger and darkly immuno-stained stellate cells mostly concentrates at central retina, while the less differentiated I3 cells, smaller and lightly immunostained irregular cells concentrate at peripheral retina. I2 cells of moderate differentiation distribute over all the retina. (2) During the postnatal development, from P1 to P13, the dense area of the TH I1 cells spreads peripherally in company with the increase of the total number of TH I1 cells, comprising the central 30% of the retina at P1, 65% at P6 and almost the whole of the retina by P13. After eye opening, as the TH I cells have spread at far peripheral region, the differences in soma diameters and dendritic maturation of TH I cells between central and peripheral retina decrease gradually and the centro-peripheral gradient of maturity of TH I cells becomes less distinct. At P23, no significant difference is visible in either soma diameter or dendritic maturation in these two areas: thus, the centro-peripheral gradient is no longer apparent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867048 TI - Straining urethral reflex: description of a reflex and its clinical significance. Preliminary report. AB - The present communication describes a reflex, which I call 'straining urethral reflex', and discusses its clinical significance. The study was performed on 17 healthy volunteers with a mean age of 39.6 years. The intrarectal pressure (representative of the intra-abdominal pressure) was measured by means of a balloon-tipped catheter introduced into the rectum and connected to a pressure transducer. A concentric needle electrode was introduced into the external urethral sphincter. The subject was asked to strain, and the urethral sphincter electromyographic activity and the intrarectal pressure were recorded. Two types of straining were investigated: sudden and slow. The procedure was repeated in 10 subjects after urethral sphincter infiltration with xylocaine or saline. On sudden straining, the external urethral sphincter contracted. The anesthetized sphincter did not respond, while the saline-infiltrated sphincter responded to sudden straining. Slow sustained straining did not evoke the reflex response. The latency of the reflex was calculated. The external urethral sphincter contraction on sudden straining guards against the involuntary opening of the vesical neck and urinary leak under stress conditions of a sudden increase in the intra abdominal pressure. The reflex may prove significant in the diagnosis of micturition control disorders. It can thus be included as an investigative tool in urologic practice. PMID- 1867049 TI - Utilization of computerized tomography for the determination of the volume of the cranial cavity of the galgo hound. AB - The volumetry of the cranial cavity of 30 galgo hounds (15 males and 15 females) has been studied by computerized axial scanning tomography and biostatistical methods. The serial tomodensitometric sections of heads were 5 mm thick and 5 mm distant, taken in sagittal and transverse planes. Results demonstrate a sexual differentiation, with a security of 99.99%. The discussion turns to zootechnical and osteoarcheological applications. PMID- 1867050 TI - Ultrastructure of the rat mesencephalic trigeminal nucleus. AB - The subcellular morphology of the mesencephalic trigeminal (Me5) nucleus in the rat was studied by transmission electron microscopy. Most neurons in the thin rostral as well as in the major caudal part of Me5 appeared as large (40-50 microns), round- to ovoid-shaped unipolar cells. A few neurons (estimated 5%) appeared to be multipolar, usually bipolar. The Me5 neurons had a large, round, centrally located nucleus, and their cytoplasm was characterized by a dense network of lamellar granular endoplasmic reticulum, an abundant Golgi apparatus, many mitochondria and neurofilaments suggesting very active cells with a high rate of synthesis and axoplasmatic transport. Numerous small spinous processes covered the surface of the Me5 neurons. Clustering of 2 or 3 cells was accomplished by maculae, i.e. zones of gap junctions and close cell appositions. Boutons contacting the soma of Me5 neurons and boutons contacting large and small dendrites were defined as axosomatic and axodendritic synapses, respectively. Four types of synaptic boutons were distinguished: (1) S boutons, with round vesicles and asymmetrical as well as symmetrical synapses, (2) F boutons, with pleomorphic admixture of flattened and spherical vesicles and asymmetrical synapses, (3) P boutons, which resembled the F-type boutons but contained predominantly spherical vesicles and symmetrical synapses, and (4) G boutons, characterized by a heterogeneous population of vesicles. This description of the Me5 nucleus is particularly useful for future studies that attempt to correlate the structure of a particular synapse with its function. PMID- 1867051 TI - Neuropeptide-Y-immunoreactive chief cells in the carotid body of young rats. AB - The immunolight- and electron-microscopic study revealed neuropeptide Y (NPY) immunoreactivity in the chief cells and a few nerve fibers of the carotid body of young rats. NPY-immunoreactive chief cells were often seen as a single cell or a group of a few chief cells in the carotid body of young rats. The immunoreaction deposits were mainly seen in the dense-cored vesicles and diffusely in the cytoplasm of the chief cells. These findings suggest that NPY may be stored in the core of granules of the chief cells of the carotid body in young rats. PMID- 1867052 TI - Expression of cholinesterase in the Schwann cells of peripheral nerves during development. AB - In peripheral nerves of mouse embryos Schwann cells exhibit a high activity of unspecific cholinesterase. At first (day 12 of embryonic development) this enzyme occurs in the nuclear envelope and in the granular endoplasmic reticulum. Thus, it is possible to differentiate between Schwann cells and fibroblasts which lack cholinesterase. Later on (day 16) the cholinesterase has shifted to the cell membrane of the Schwann cells. However, only that part of the plasmalemma which encircles single axons and the mesaxons exhibits an irregular deposition of the reaction end product. In newborns the first loops of the just formed myelin sheath are still stained. With maturation of the myelin sheath the enzyme activity disappears. The functional role of cholinesterase is unclear. Possible roles are discussed. The expression of cholinesterase in Schwann cells depends on the integrity of the axons. After a few hours, the cultivation of amputated limbs results in a reduction of the enzyme activity. After 1 day in culture cholinesterase disappears totally. PMID- 1867053 TI - Monoclonal antibodies against a human juxtaglomerular epithelioid granular cell tumour. AB - With the exception of the renin-angiotensin system, the molecular composition of juxtaglomerular epithelioid granular cells (JEG cells) is unknown. We demonstrate the molecular peculiarities of these modified smooth muscle cells using monoclonal antibodies produced against a benign human JEG-cell tumour. Six out of 29 different clones produced antibodies that label JEG cells nearly exclusively. Antibodies from the other clones recognize JEG cells but also granularly or homogeneously distributed antigens of proximal tubule cells. This suggests antigenic similarity between granules of JEG cells and lysosomes of proximal tubule cells. Other clones produce antibodies which tag different cytoplasmic membranes or even mast cells. The antibodies directed exclusively against JEG cells promise to be useful tools to study their physiology and pathology. PMID- 1867054 TI - Ontogeny of cholinergic ganglionic cells which take up L-3,4 dihydroxyphenylalanine and contain vasoactive intestinal polypeptide in the mouse tongue. AB - During the prenatal development of the mouse tongue, the intralingual ganglion was investigated histochemically and immunohistochemically for acetylcholinesterase (AChE) activity, the capacity to take up L-3,4 dihydroxyphenylalanine (L-DOPA) and vasoactive intestinal polypeptide (VIP)-like immunoreactivity. AChE-positive cells were first observed at gestational day 12, and AChE-positive neurons which take up L-DOPA were found at gestational day 14, while VIP-like immunoreactive neurons were not seen until gestational day 16. The present results suggested that the cholinergic neurons within the mouse tongue can take up L-DOPA from gestational day 14 and synthesize VIP from gestational day 16. PMID- 1867055 TI - A model to predict canine pelvic limb musculoskeletal geometry. AB - We developed a model to predict the three-dimensional canine pelvic limb muscular geometry (i.e., all muscle moment arms during any instant in gait). Forty-one muscle origins and insertions, as well as external landmarks (to obtain anthropometric dimensions) were marked on both pelvic limbs of five dogs and digitized on biplanar radiographs. Reference frames in the pelvis, femur, and tibia established the three-dimensional coordinates of each origin, insertion, and landmark. A set of dimensionless 'scaled coordinates' was created by dividing the actual origin and insertion coordinates by selected anthropometric dimensions of each animal. Combining scaled coordinates from all ten limbs produced an averaged 'template' of scaled coordinates. To provide limited validation of the scaling procedure, we measured the anthropometric dimensions between externally palpable landmarks of two additional pelvic limbs. The anthropometric dimensions were multiplied by the averaged template coordinates to calculate two new sets of hindlimb muscle coordinates within the three bony reference frames. The two limbs then were dissected, muscle endpoints were marked, and biplanar radiographs of each of the limb segments were digitized. The actual coordinates so obtained were similar to those predicted by the template and anthropometric measures. PMID- 1867056 TI - Microcirculation of the rat omentum studied by means of corrosion casts. AB - A study of the microvasculature of the omentum using corrosion casts was undertaken. The object was to supply information regarding the morphology of the three-dimensional structure of the microvasculature, information which may be valuable in understanding the functions of the omentum. Corrosion casts of rat omenta were prepared and studied. Characteristic glomerular-like capillary beds were identified. Some of these beds were densely and others loosely arranged. Two types of capillaries made up these beds, tortuous and straight capillaries. These beds also showed a planate surface giving the impression that they lie directly under the mesothelium. PMID- 1867057 TI - Effects of low-power gallium aluminium arsenide diode laser irradiation on the development of synapses in the neonatal rat hippocampus. AB - The effect of low-power gallium aluminium arsenide diode laser irradiation on the development of synapses was studied in the radiatum layer and the lacunosum molecular layer of field CA3 of the neonatal rat hippocampus. Neonatal rats were irradiated with a low-power diode laser (830 nm, 60 mW) at two points located above the hippocampi, for 15 s, respectively, twice per day from birth (day 1) to day 5. The mean body weights of the laser-irradiated animals were found to be lower than those of the control animals, the deficit at day 20 being 22.6%. Moreover, the density of synaptic junctions stained by ethanolic phosphotungstic acid per unit area of the radiatum layer and the lacunosum-molecular layer of the neonatal rat hippocampus was significantly reduced at day 20. It was suggested that the low-power diode laser irradiation affected the development of synapses in the neonatal rat brain. PMID- 1867058 TI - Unusual membrane-bound bodies in the basal lamina of the uriniferous tubules of the camel Camelus dromedarius. Freeze-fracture and ultrathin-section study. AB - Kidney samples of the camel Camelus dromedarius were aldehyde fixed and glycerol impregnated for ultrathin-section and freeze-fracture studies of the basal lamina. Results obtained show the presence of extracellular membrane-bound bodies within the thick basal lamina of the tubular portion of the nephron. The 10- to 500-nm bodies appear isolated and are found at various levels along the width of a highly structural lattice basal lamina. The bodies are observed either in small groups or as single structures which are invariably surrounded by a clear halo of the basal lamina. In ultrathin sections they appear limited by a typical unit membrane structure, and their interior may appear empty or may exhibit material of variable electron opacity. Freeze-fracture replicas reveal the limiting membrane of the bodies which appear either as concave or convex structures. Intramembrane particles (IMPs) measuring between 5 and 15 nm are present in some of the bodies, whilst others appear devoid of IMPs. The IMPs are present in both concave and convex surfaces and are usually aggregated into clumps. The region of the basal lamina which contains the membrane-bound bodies is usually granular except in the area immediately surrounding the bodies which corresponds to the clear halo observed in thin sections. Although these basal lamina membrane-bound bodies appear to be similar to matrix vesicles previously described in mineralizing tissues, it seems unlikely that they are involved in calcification. It is possible that the membrane-bound bodies and the highly configurated basal lamina may be related to ionic transport mechanisms which are associated with the high osmolarity of the camel urine. PMID- 1867059 TI - [CCL-tensulae in the skeleton as part of a hydrodynamic skeletal system]. AB - Previous morphological studies on human bone have demonstrated that veil-like structures ('tensulae') occur in highly stressed regions, i.e. the interface between cartilage and bone. In the present report we describe the distribution of tensulae within various types of human bone by means of scanning electron microscopy and light microscopy. Tensulae were predominately located within bone tissue adjacent to mineralized cartilage. The surface diameter of tensulae ranged from minimal 50 to maximal 400 microns. Occasionally, collagen fibers extended from the interface between cartilage and bone to tensulae. Frequently, the latter were attached to fat cells as well as bone marrow cells. An elemental analysis of tensula revealed high levels of calcium and phosphorus of equal concentrations. However, bone tissue contained higher levels of calcium compared to phosphorus. Additionally, a monoclonal antibody was generated by immunizing rats with bone marrow of mice. Within bone tissue this monoclonal antibody selectively stained membrane-like structures which were clearly identified as tensulae. From our investigations we conclude that the function of tensulae in bone may be to absorb stress in regions where large forces are applied. PMID- 1867060 TI - Morphometric evaluation of chondrocyte cavities in normal and prearthrotic human femoral heads. AB - In 25 human femoral heads, the structural changes in the chondrocyte cavities of prearthrotic cartilage were determined in three different layers by detailed morphometric evaluation. As examination parameters, the area, perimeter, diameter, and the form deviation from a circle (form PE) were chosen. In addition, we calculated the numeric cell density and the mean distance between two chondrocyte cavities. For intraindividual comparison, the same data were obtained from nondegeneratively changed cartilage areas of each femoral head. The main arthrotic regions were located in the weight-bearing area of the femoral head, particularly in the dorso- and ventrolateral quadrants. The number of chondrocyte cavities as well as the numeric cell density were decreasing from superficial to basal layers, whereas the mean distance between two chondrocyte cavities was increasing. Concerning these parameters, no significant differences were seen between the prearthrotic and control groups. We found that the chondrocyte cavities in the superficial layer in prearthrotic areas show a tendency to smaller volumes in comparison with nondegeneratively changed areas, whereas in the basal layer, no difference could be seen. We presume that the changes in the articular cartilage are not related to an insufficient supply of the cartilage with nutriments, but probably to the high mechanical strain applied to its surface. PMID- 1867062 TI - Muscle architecture and intramuscular distribution of nerves in the human soleus muscle. AB - On the deep anterior surface of the human soleus muscle a bipenniform part is found, the portio anterior, which is innervated by the ramus anterior. This part and the innervation pattern are morphological characteristics peculiar to man. In six human soleus muscles plus three anomalies, the intramuscular distribution of the nerves supplying these muscles was macroscopically examined. In the normal soleus muscles, the R. anterior supplied not only the portio anterior but also the portio posterior through several anastomoses with twigs of the R. posterior. In the soleus without the portio anterior, the R. anterior entered the muscle at the anterior surface and joined directly with the branches of the R. posterior. In the soleus with two bipenniform parts, one bipenniform part was supplied by the R. anterior, and the other by the R. posterior. The cross-sectional area of the total nerves supplying the muscle was 0.72 +/- 0.036 mm2 (n = 8). The areas of the R. posterior and the R. anterior were in inverse relation to each other. These findings suggest that the R. anterior became separated from the R. posterior. However, the endoperineurium fiber composition of the R. anterior appeared to consist of a few nerve fiber components different from those of the R. posterior. PMID- 1867061 TI - Effects of castration and sex steroids on sexually dimorphic development of the mouse submandibular gland. AB - The aims of this study were to characterize sexual dimorphism in the submandibular glands of young adult mice and to determine how sex differences arise during postnatal development. In the mouse submandibular glands, prominent sexual dimorphism was observed at 30 days of age, when the male gland was superior in both the relative occupied area (ROA) and the mitotic rate of the granular convoluted tubules (GCT) to those of the female. By neonatal castration, this sexual dimorphism was abolished, and the intraglandular structures of castrated males were similar to those of normal females. In castrated mice of both sexes, daily treatment with testosterone and 5 alpha-dihydrotestosterone for 10 days from 20 days induced only the ROA of the GCT to increase to the normal male levels but not those of the other three regions of the glands, the acini, intercalated ducts and excretory striated ducts. Testosterone responsiveness of the glands, considering both the glandular weight gain and the mitotic rate of the GCT, was significantly higher in castrated males than in castrated females. On the other hand, 17 beta-estradiol had no effect on the glands of castrated mice. Therefore, the present study suggests that the testicular hormones are responsible for the masculine development of GCT of the glands, but not the ovarian hormones, and that there is a sex difference in the responsiveness of the glands to testosterone, which is more effective in males than in females. PMID- 1867063 TI - Comparative mapping of acetylcholinesterase and reduced nicotinamide adenine dinucleotide diaphorase in the rabbit dorsal thalamus. AB - The distribution of acetylcholinesterase and reduced nicotinamide adenine dinucleotide (NADH) diaphorase enzymatic activities was mapped histochemically in the dorsal thalamus of the rabbit. A comparison of the resulting patterns helped in the histochemical delimitation of a number of nuclei, as well as in the detection of some subdivisions, that showed differential expression of these enzymes. It was observed that AChE and NADH diaphorase tend to appear in a complementary fashion in many dorsal thalamic neuropiles, so that intense activity of the one was accompanied by low activity of the other. However, coincident expression of both enzymes was also obtained in a small number of areas. The correlation of these patterns with other chemo-architectonic and hodologic data does not yet disclose an explanation of these regularities, which however suggest some functional significance. PMID- 1867064 TI - Differential patterns of incorporation and remodeling among various types of bone grafts. AB - The early (3 months) and later (6 months) patterns of incorporation and bone formation have been evaluated histomorphometrically for different types of bone grafts; that is, vascularized and nonvascularized autografts with and without ciclosporin, and vascularized and nonvascularized dog leukocyte antigen (DLA) mismatched allografts with and without ciclosporin. The vascularized bones were superior to the nonvascularized ones in healing and remodeling their grafted segments. In the autograft bones, ciclosporin did not alter the incorporation process 3 months after transplantation but delayed and increased the remodeling activities in the long run (6 months). Nonvascularized allografts underwent vigorous resorption, and were markedly porotic. Ciclosporin administration significantly reduced resorption and enhanced remodeling in nonvascularized allografts. The remodeling of allografts was similar to that of autografts in the presence of ciclosporin, but stopped soon after the administration of ciclosporin ceased. PMID- 1867066 TI - Microglial cells in the central nervous system of the rabbit and rat: cytochemical identification using two different lectins. AB - Microglial cells were selectively demonstrated in the central nervous system of adult rabbits and rats using lectin histochemistry. Biotinylated Ricinus communis agglutinin-120 (RCA-1) and biotinylated Griffonia simplicifolia B4 isolectin (GSA I-B4) were used as histochemical markers on sections of Bouin-fixed paraffin embedded cerebrum and cerebellum. Results were quite similar using both lectins and both species. GSA I-B4 resulted in a better staining in the rat, while RCA-1 labelling was superior in the rabbit. Neither neurons nor glial cells other than microglia were stained with our technique. Lectin histochemistry applied for the detection of microglial cells appears to be of sufficient selectivity and may be considered as an important tool in the morphological and neurobiological study of these cells. PMID- 1867065 TI - Orientation of adhering junctions between bovine pulmonary fibroblasts. AB - The ultrastructure and orientation of microfilament-attaching junctions between pulmonary fibroblasts (also known as myofibroblasts or contractile interstitial cells) of bovine lung septa were investigated by transmission electron microscopy. Adhering junctions similar to the fascia adherens of the intercalated disc, but of a macular design, link microfilament bundles of adjacent fibroblasts. The bundles of microfilaments joined by junctions were usually aligned perpendicularly to the axis of the alveolar wall. Gap junctions were located in close proximity to the adhering junctions, presumably to co-ordinate the contraction of the cells. The data indicate that fibroblasts are able to form multicellular contractile units within healthy, mature lung parenchyma. PMID- 1867067 TI - Protein-secretory patterns of normal and abnormal human placentas with special reference to human chorionic gonadotropin. AB - [35S]Methionine-labeled protein-secretory patterns resolved by two-dimensional polyacrylamide gel electrophoresis in abnormal hydatidiform-mole placentas were compared with those in normal full-term placentas with special reference to human chorionic gonadotropin (hCG) by means of immunoblotting and immunoelectron microscopic techniques. Although basic protein-secretory patterns of both placentas were similar to each other, four polypeptide spots appeared and one spot disappeared in the hydatidiform-mole samples. Among four newly synthesized and secreted spots, three were immunoreacted with anti-hCG serum by an immunoblotting experiment. Ultrastructural localization of hCG showed that the labeling intensity of anti-hCG serum in hydatidiform-mole placentas was much heavier than that in full-terms ones. Particularly, the Golgi apparatus, middle sized granules and large bodies were highly immunoreactive. The present study reveals that hydatidiform-mole placentas have different protein-secretory functions especially in hCG synthesis and secretion from those of normal pregnancy. PMID- 1867068 TI - Optimal replacement of the cruciate ligaments from the functional-anatomical point of view. AB - By means of a combined technique of dissection and radiography, the function of cruciate ligament fibers was analyzed for motions in the sagittal plane, and different functional fiber bundles were reconstructed in cadaver knees. In order to grant permanent stability, crucial replacement must be concentrated on the reconstruction of the constantly taut 'guiding bundle' of each cruciate ligament. The femoral attachment point of each guiding bundle was found to be in a constant position within the femoral attachment of the respective cruciate ligament. The femoral attachment areas of different functional fibers are also defined geometrically, and the consequences of improper guiding bundle replacement are discussed. PMID- 1867070 TI - Branches of the left pulmonary artery supplying the basal segments of the lung. AB - The studies were carried out on 100 left lungs taken from dead human bodies of both sexes whose age varied from 16 to 80 years. The pulmonary artery and the bronchus were injected with a 65% solution of duracryl and then digested in sulfuric acid. The specimens obtained were then examined to determine the number and dimensions of the branches of the basal portion of the left pulmonary artery penetrating into the basal segments of the left lower pulmonary lobe. Their length was 60 mm at the most, and their diameter 9.8 mm. Three types of ramification of the basal portion of the left pulmonary artery were distinguished on the basis of the trunks, segmental and subsegmental branches present. In 70% of the cases the branches penetrating into the basal segments showed tree-like type, in 3% of the cases showed bushy-like type, and in 27% of the cases middle type. PMID- 1867069 TI - Postnatal effects of nicotine on first molar development in the CD-1 mouse. AB - Young CD-1 mice, 4 days old, exposed to 0.1% nicotine sulfate on gestational days 6-20 were compared with untreated pups of the same age to determine its effect on the development of mandibular first molars. Pregnant mice were given intraperitoneal injections of nicotine at a dose of 1.67 mg/kg/day. Pups were then decapitated, their entire mandibles were excised, routinely prepared and embedded in paraffin, sectioned in the frontal plane and stained with hematoxylin and eosin for histological examination of developing lower first molars. The results demonstrated that the process of odontogenesis appears retarded in nicotine-treated animals while the molars of the control group revealed dentin and enamel formation. It was concluded that nicotine has a detrimental effect on molar development. Nicotine may interfere with cellular maturation of the tooth germ indicating that this effect is prenatal and extends postnatally. PMID- 1867071 TI - Atrioventricular and ventriculoatrial branches of the coronary arteries in human hearts. AB - Atrioventricular (AV) and ventriculoatrial (VA) branches of the coronary arteries are vessels which supply simultaneously atrial and ventricular walls by means of recurrent rami. The terminology indicates the name of the main vessel followed by the name of the recurrent vessel both combined in an adjective. These branches establish a vascular 'suture' across the coronary sulcus in front (superficially to) or behind (deeply to) the trunks of the right coronary artery and of the left coronary artery (circumflex artery). The AV and VA branches, found in 95% of 40 human hearts, should be considered a normal characteristic of the coronary circulation and an important anatomical factor for the clinical interpretation of pathological cardiac phenomena. PMID- 1867072 TI - Epidemiological studies of childhood insulin dependent diabetes. PMID- 1867073 TI - A discordant movement in urine calcium excretion in relation to serum calcium and parathyroid function occurring immediately after birth. AB - We studied the relationship between serum calcium and urinary calcium excretion in association with the parathyroid function in 28 neonates at birth and at five days of age. At birth, the urine calcium was low in spite of high cord serum calcium and a low parathyroid hormone level. On the fifth day of birth, urinary calcium excretion increased despite the reduction in serum calcium and an increase in the parathyroid hormone. These results suggest that the large increase in renal blood flow and the consequent increase in calcium load on the immature renal tubule occurring after birth may be the main cause for the change in this serum calcium-urinary calcium relationship. This finding can in part explain the temporary hypocalcemia during this period. PMID- 1867074 TI - Neonatal sepsis in Pakistan. Presentation and pathogens. AB - The case records of all neonates admitted to the neonatal unit at Aga Khan University Hospital (Karachi) in a 30 month period (Nov. 86-April 89) were analysed. Of 60 neonates with confirmed sepsis, 33 (55%) had non-nosocomial infection (NNC) whereas 27 (45%) had nosocomial sepsis (NC). The most common organisms causing early-onset NNC sepsis were Klebsiella species (53%) and Escherichia coli (10%), whereas the organisms causing late-onset NNC sepsis included Salmonella parathypi (21%), Group A Streptococcus (21%), Escherichia coli (14%) and Pseudomonas species (14%). Klebsiella was the most common organism causing NC sepsis, others being Staphylococcus aureus (15%) and Serratia species (15%). The mortality in NC sepsis, early-onset and late onset NNC sepsis was 44%, 26% and 43%, respectively. Risk factors associated with NNC sepsis included low birthweight, prematurity and prolonged and complicated deliveries. There was a high incidence of drug resistance to ampicillin and gentamicin among gram negative organisms causing sepsis (mean 67%). PMID- 1867076 TI - Effects of indomethacin on cerebral hemodynamics at rest and during endotracheal suctioning in preterm neonates. AB - The effect of therapeutic doses of indomethacin versus placebo (saline) on cerebral hemodynamics was studied in nine mechanically ventilated preterm infants. Recordings were made at rest and during endotracheal suctioning. Indomethacin at a dose of 0.2 mg/kg body weight was infused over 5 min. Compared to placebo, there was a significant decrease in Doppler mean frequency in the anterior cerebral artery within minutes of starting the indomethacin infusion during the resting period after the first (p less than 0.01), second (p less than 0.001) and third (p less than 0.025) doses. This effect has persisted during endotracheal suctioning. Thus, indomethacin alters cerebral hemodynamics by decreasing Doppler mean frequency. In view of these findings, and particularly because of the alteration in the resting cerebral hemodynamics, the recommendation of prophylactic treatment with indomethacin remains questionable. PMID- 1867075 TI - Intestinal colonization with Enterobacteriaceae in Pakistani and Swedish hospital delivered infants. AB - Rectal cultures from Swedish and Pakistani hospital-delivered newborn infants were analysed regarding the early acquisition of enterobacteria. Swedish infants were delivered vaginally, Pakistani infants were delivered either vaginally or by caesarean section. The Swedish infants were all breast-fed, whereas breastfeeding was incomplete and often started late among the Pakistani infants. Both groups of Pakistani infants were more rapidly colonized with enterobacteria than were the Swedish infants. Cultures from Swedish infants seldom yielded more than one kind of enterobacteria; E. coli and Klebsiella were most frequently isolated. E. coli dominated in both Pakistani groups, but especially caesarean section delivered infants were in addition often colonized with Proteus, Klebsiella, Enterobacter or Citrobacter species. Breastfeeding from the first day of life reduced colonization with Klebsiella/Enterobacter/Citrobacter. The results suggest that environmental exposure, delivery mode and early feeding habits all influence the early intestinal colonization with enterobacteria. PMID- 1867077 TI - Subcapsular hemorrhage of the liver in the very low birthweight neonate. AB - Between 1974 and 1989, 15 neonates were found, at autopsy, to have subcapsular hematoma of the liver in a retrospective clinicopathologic study of 644 neonates. The majority (75%) of the neonates were less than 28 weeks gestation, male gender, and were delivered by the vaginal route following a complicated pregnancy and labor including malpresentation. The clinical course included resuscitation at birth, ventilatory support and hypovolemic shock with death occurring within 24 hours in 11 neonates. Other clinical events included air leak (n = 4 infants) and infection (n = 4). Intracranial hemorrhage was suspected in all but was found at autopsy in 8 neonates. The subcapsular hematoma was intact in 7 and ruptured in 8 neonates. Hence, subcapsular hemorrhage of the liver should be considered in the differential diagnosis of hypovolemic shock in very low birthweight infants. PMID- 1867078 TI - Circulating blood volume in appropriate and small for gestational age full term and preterm polycythaemic infants. AB - Relative circulating volume (CV) was determined in 31 polycythaemic newborn infants who underwent a partial plasma exchange transfusion (PPET). The infants were divided in four sub-groups: appropriate for gestational age (AGA) term and preterm infants, and small for gestational age (SGA) term and preterm infants. CV was calculated using a regression line between the number of exchange steps and central venous haematocrit values obtained before the procedure and after every exchange step. The median relative CV in all polycythaemic newborn infants was 94.0 (range 69-143) ml/kg. Irrespective of gestational age and birthweight the median relative CV in AGA infants was 86.5 (range 69-107) ml/kg, which differed significantly from the value of 106 (range 85-143) ml/kg found in SGA infants. If a PPET is indicated we recommend to calculate the exchange volume in AGA infants using a relative CV of 86 ml/kg and in SGA infants using a relative CV of 106 ml/kg. PMID- 1867079 TI - Hyaline membrane disease and early neonatal aldosterone metabolism in infants of less than 33 weeks gestation. AB - We studied urine excretion of free and conjugated aldosterone by 12 control infants and 14 infants with hyaline membrane disease (HMD) on the first and seventh days after birth. Both groups had a mean gestational age of 29 weeks. Total urine aldosterone excretion (UAE) and percent excreted as conjugate were similar for both groups on both study days, and did not relate to the severity of respiratory failure in infants with HMD. Sodium intake was higher for infants with HMD on both study days (p less than 0.02), but their urine sodium excretion was only significantly (p less than 0.01) higher on day 7. For total UAE values greater than 3 nmol/kg/d, there was no significant difference between estimated sodium-potassium exchange by control (22 +/- 5%, n = 8) and HMD (31 +/- 5%, n = 10) groups. These data suggest that neither the magnitude of excretion of aldosterone in the urine, the ability to conjugate aldosterone nor the degree of relative distal tubular unresponsiveness to aldosterone are related to the severity of pulmonary immaturity in preterm infants. PMID- 1867080 TI - Vitamin D metabolism in pre-operative extrahepatic biliary atresia. AB - In order to clarify the pathogenesis of rickets in preoperative patients with extrahepatic biliary atresia, we evaluated baseline serum 25-OHD and 1,25(OH)2D levels and correlated serum 25-OHD levels with increase in age and season of birth in 16 preoperative patients. Further, parenteral vitamin D2 tolerance tests were performed in 5 cases. Serum 25-OHD and 1,25(OH)2D levels were significantly lower than those in 15 normal controls. There was a negative correlation between the serum 25-OHD levels and increase in age. The patients born during the winter had lower serum 25-OHD concentrations than those born in summer. The mean value of increased 25-OHD levels after the parenteral vitamin D2 tolerance tests did not differ from that of 6 controls. Since there was no impairment of vitamin D 25 hydroxylation, the reduction in serum 25-OHD may therefore be mainly due to disturbed intestinal vitamin D absorption. It was also concluded that season of birth and increase in age are pathogenic factors in the etiology of rickets in preoperative patients with extrahepatic biliary atresia. PMID- 1867081 TI - Inflammatory bowel disease in children and adolescents: a somatic and psychiatric investigation. AB - Twenty consecutive patients between 9 and 18 years of age with inflammatory bowel disease (IBD) [ulcerative colitis (UC) or Crohn's disease (CD)] were assessed for the presence of psychiatric disorder. The prevalence of psychiatric disorder using the DSM-III-R criteria (Diagnostic and Statistical Manual 3rd ed., revised), was 60% in the IBD group compared to 15% in a matched control group (p = 0.009). The psychiatric disturbances were mainly depressive or anxiety disorders. The IBD children also scored significantly higher (p = 0.0028) on the Child Behaviour Checklist (CBCL) which was completed by the mothers. This indicates more behavioural problems in the IBD group than in the control group. The present study suggests that children and adolescents with IBD comprise a population at high risk for developing a psychiatric disorder that may not be overt but nevertheless plays an important interactive role in the course of the disease. PMID- 1867082 TI - Single dose treatment of cystitis in children. AB - The efficacy of single dose treatment with trimethoprim compared to a 5-day course with the same drug was investigated in 100 children, 3-12 years, with isolated episodes of symptomatic non-febrile urinary tract infection. Cure, defined as sterile urine during the first week after treatment, was achieved in 74% (37/50) in the single dose group compared to 86% (43/50) in the 5-day treatment group. The difference was not statistically significant (chi 2 = 2.25, p = 0.134 two-tailed). The cure rates in relation to P-fimbriation of the infecting E. coli strains were similar in the two groups. During the 6 month follow-up, six children in each treatment group had one or more reinfections. Extended studies are needed to conclude if single dose and conventional treatment courses are equally effective. PMID- 1867083 TI - Deficiency of IgG subclasses and IgA, and elevation of IgE in children with a past history of bacterial meningitis. AB - Of 44 children who recovered from an attack of bacterial meningitis, 3 (7%) were found to have IgG subclass deficiency, 5 (11%) had IgA deficiency and 22 (50%) had raised IgE levels. These results suggest that immunoglobulin abnormalities may be an important predisposing factor in some cases of bacterial meningitis. PMID- 1867084 TI - Immunological markers in the cerebrospinal fluid of HIV-1-infected children. AB - Several immunological abnormalities were detected in the cerebrospinal fluid (CSF) of human immunodeficiency virus type 1 (HIV-1)-infected children. Intrathecal synthesis of immunoglobulins, free light chains (FLC), IL-1 beta, IL 6, and M-CSF were demonstrated both in asymptomatic children and children with subacute encephalopathy. Our findings further support the hypothesis that an immunopathological subclinical process within the central nervous system (CNS) may be an early manifestation of acquired immunodeficiency syndrome (AIDS). Cytokine detection in the CSF may represent a useful diagnostic tool in evaluating the outcome of HIV-1-infected patients. PMID- 1867085 TI - Blood lipids and diet in Swedish adolescents living in Norsjo, an area with high incidence of cardiovascular diseases and diabetes. AB - In Norsjo in Northern Sweden a cardiovascular intervention programme, for adults is presently tested. The aim of the present study was to investigate the presence of factors related to cardiovascular disease in all 15-year-old adolescents living in Norsjo in 1987 and 1988. The total cholesterol concentration in serum, as an average for the test period, was 4.2 mmol/l and 4.7 mmol/l for boys and girls, respectively. Fourteen per cent of the boys and 32% of the girls had a total cholesterol concentration exceeding 5 mmol/l. Twenty-seven per cent of the adolescents had high values for two or more variables related to risk of developing cardiovascular disease. The evaluation of the dietary registrations showed unsatisfactory values for fibre, P/S ratio and total fat. The dietary habits were better in the 15-year-olds in 1988 than in 1987 as judged by significantly higher average daily intake of fibre as well as a higher content of fibre per megajoule in the food. PMID- 1867086 TI - Lipoprotein alterations and plasma lipoprotein lipase reduction in familial hemophagocytic lymphohistiocytosis. AB - Serum lipid abnormalities are common in familial hemophagocytic lymphohistocytosis (FHL), a disorder also characterized by fever, hepatosplenomegaly, pancytopenia and a prominent lymphohistiocytic accumulation in the mononuclear phagocyte system. The lipoprotein pattern in nine children with FHL was studied with a quantitative method measuring cholesterol and triglycerides in each major class of lipoproteins. Triglycerides were markedly elevated during active FHL in serum, very low density lipoproteins, and low density lipoproteins. Cholesterol was increased in very low density lipoproteins whereas both triglycerides and cholesterol were extremely low in high density lipoproteins. These lipoprotein abnormalities, reversible on successful therapy, are compatible with a depressed lipolytic activity. Post-heparin levels of lipoprotein lipase and hepatic lipase in plasma were studied in four children and found to be markedly low during active FHL. We suggest that inflammatory cytokines, which may strongly suppress lipoprotein lipase activity, can be important mediators in the pathophysiology of FHL and that they may participate in the development of the lipid abnormalities. PMID- 1867087 TI - Quantitation of muscles and fat by ultrasonography: a useful method in the assessment of malnutrition in children. AB - We used ultrasonography to measure muscles in the arms and thighs of 16 children with malignant diseases. Thicknesses of transverse sections of the brachial biceps muscle and the femoral quadriceps muscle were measured by ultrasound at the midpoint of the right arm and thigh. These two measures had a linear correlation (r = 0.76). The ultrasound measurements did not differ from those obtained by the CT scan which was used as a reference standard. The reproducibility of the measurements was good; the coefficient of variation was 2.4% for the midarm muscles and 2.8% for the midthigh muscles. We conclude that the ultrasound method combined with simple anthropometric measurements is helpful in the assessment of nutritional status of children with potential malnutrition. PMID- 1867088 TI - Respiratory tract infections in children with recurrent episodes as preschoolers. AB - The occurrence of respiratory tract infections (RTI) in 41 school-age children, who had recurrent RTIs treated with antibiotics as preschoolers, was followed prospectively for two years through diary reports by parents and medical consultations, and compared with that in 29 children of the same age and socio economic background, who had few or no such infections as preschoolers. During the two-year follow-up, a greater number of episodes of RTI and a longer mean duration of such episodes were reported in the diaries concerning the children with recurrent bacterial RTIs as preschoolers compared with the controls (p less than 0.01). The annual incidence of bacterial RTI from birth onwards decreased with age among the children with recurrent episodes as preschoolers, unlike in the control group, where the incidence remained consistently low, the difference in incidence being significant up to the age of eight years (p less than 0.01). Acute otitis media was the predominant bacterial RTI in preschoolers, and acute tonsillitis in school-age children. There was a tendency toward a greater incidence of other types of disease and complications/sequelae of infections among the RTI-afflicted group than among the controls, both as preschoolers and as school children. Our findings suggest that certain children constitute a group with high morbidity, susceptible to RTIs and other illnesses over a rather long period of years. PMID- 1867089 TI - Children with recurrent respiratory tract infections tend to belong to families with health problems. AB - Children (7-11 years of age) who had recurrent respiratory tract infections (RTI) treated with antibiotics as preschoolers (n = 41), and their families were compared with regard to medical and social factors to families with children of comparable age who had had no such infections as preschoolers, or only isolated episodes (controls; n = 29). All the children studied had attended day-care centres as preschoolers. The two groups of children did not differ with regard to socio-economic conditions or age at admission to day-care centres. There was a difference in the two groups with regard to signs noted at physical examination (p less than 0.05), eardrum changes being observed in 34% of the children with recurrent episodes of RTI as preschoolers and in none of the controls (p less than 0.001). Questionnaires answered by parents indicated diseases, particularly cardiovascular diseases, to be significantly more frequent in the families of the children with recurrent RTIs as preschoolers than in those of the controls (p less than 0.01). Parents of the controls were more often satisfied with their own health (p less than 0.05) and reported fewer symptoms of minor illness (p less than 0.05), as compared with parents of the children with recurrent RTIs as preschoolers. Thus, the results of the present study support the idea that children with recurrent bacterial RTIs as preschoolers tend to belong to families with health problems. PMID- 1867090 TI - Respiratory illness in children: do deprived children have worse coughs? AB - Parents of a stratified random sample of 234 children from 21 general practices in North East England were interviewed at home. All these children had been reported in a postal questionnaire as having had a cough between six and ten weeks before the interview. Interviews covered social characteristics of the family, the severity of the child's cough and the reactions of the parents to hypothetical sets of symptoms. The parents of children in materially deprived circumstances appeared to report worse coughs than other parents. We confirmed this finding by constructing a scale of perceived cough severity. However, we found no evidence that the inequality was due to exaggeration of the severity of the cough by materially deprived parents. Our conclusion that materially deprived children suffer worse respiratory illness is the more important because previous evidence suggests that the after-effects persist into adulthood. PMID- 1867091 TI - Oestrogen treatment of tall girls: effect decreases with age. AB - Fifty-nine tall girls were treated with oestrogen to reduce final height, starting at the ages of 9.1 to 16.2 years. We assessed the result of this treatment by comparison with matched controls. The epiphyseal bone age at the start of therapy, the final height, the Bayley-Pinneau (BP) and Roche-Wainer Thissen (RWT) predictions of final height, and the errors in both predictions were evaluated. The matched pairs were divided into three groups according to bone age at the start of treatment; I less than 10.5 (n = 16), II 10.5-12.0 (n = 22) and III greater than 12.0 years (n = 21). The mean (SD) intrapair reduction of height for these groups was 9.7 (4.0) cm, 4.3 (4.3) cm and 3.5 (3.2) cm, respectively, according to BP predictions and 6.3 (4.3) cm, 3.4 (3.0) cm and 1.2 (3.3) cm according to RWT predictions. No method of predicting height is accurate for tall girls and simultaneous predictions may differ greatly. Close agreement between the BP and RWT predictions does not indicate greater accuracy. The earlier therapy is started, the greater is the effect. Young girls need psychosocial support with therapy. PMID- 1867092 TI - Incidence of childhood insulin-dependent diabetes mellitus in Lithuania 1983 1988. PMID- 1867093 TI - Home-made oral rehydration solutions: variations in composition. PMID- 1867094 TI - Asthma as the first presenting symptom of complex glycerol kinase deficiency. AB - Two patients presenting with asthma as the first clinical symptom of a mild form of Addison crisis were found to have complex glycerol kinase deficiency (CGKD). They had been treated with bronchodilators prior to the exact diagnosis. Asthma may appear in a mild form of Addison crisis in a patient with CGKD. Pediatricians should be aware of this unusual presentation of CGKD. PMID- 1867095 TI - Congenital agammaglobulinemia presenting with ecthyma gangrenosum. AB - Two males with presumed X-linked agammaglobulinemia (X-LA) presented with ecthyma gangrenosum. This is an unusual presentation of this syndrome. Possible causes are discussed. PMID- 1867096 TI - Radiocontrast-induced nephropathy in a pair of xiphaomphalopagus conjoined twins during the neonatal period. AB - One of the babies in a pair of xiphaomphalopagus conjoined twins developed oliguria, transient rise in serum creatinine and persistent nephrogram on the sixth day of life following injection of radiocontrast medium for computerised axial tomography scanning of the urinary system. The other twin was spared but developed hypertension and "dialysed" the oliguric twin. The renal profiles of both neonates subsequently remained normal until they reached adequate weight for surgical separation at a later date. PMID- 1867097 TI - Enzyme-induced aggregation and disaggregation of tumor cells via the cell surface glycocalyx in association with deoxyribonucleic acid. AB - Serine proteases cause aggregation of the rat ascites tumor cell lines AH-130, AH 109A and YS in vitro, and the tumor cell aggregates are dissolved by treatment with DNase I. We previously demonstrated that these events played a critical role in the augmentation or reduction of experimental blood-borne metastasis of these cell lines. In the present study, the ultrastructural features of this protease dependent aggregation were analysed. Transmission and scanning electron microscopy revealed that after the protease treatment each tumor cell was surrounded by a thin membranous (sleeve-like) structure. This sleeve-like structure was stained with ruthenium red to an intensity similar to the cell surface of the control. Adjacent cells became attached to each other with microvilli via this fine structure. Immuno-electron microscopy revealed DNA antigen as dense patches on the sleeve-like structure or as faint and diffuse deposits on the outer surface of the cells by indirect immunoperoxidase staining using an anti-DNA monoclonal antibody. Both the sleeve-like structure and immunopositive deposits disappeared after treatment with DNase I. Neither cell viability nor the normal ultrastructure of their organelles was influenced by the enzyme treatment. These results indicate that serine protease-induced tumor cell aggregation is due to cellular contact via the sleeve-like structure, which probably originates from the cell surface glycocalyx in association with DNA molecules of unknown origin. PMID- 1867098 TI - Immunohistochemical demonstration of epidermal growth factor receptor and ceruloplasmin in thyroid diseases. AB - The expression of epidermal growth factor receptors (EGFR) and ceruloplasmin (CP) in thyroid diseases was investigated by immunohistochemical methods, and the results were compared with the expression of thyroglobulin (TG). Eighty-eight surgical specimens of thyroid diseases, including follicular carcinoma (7 cases), papillary carcinoma (20 cases), follicular adenoma (29 cases), adenomatous goiter (10 cases), diffuse hyperplasia (20 cases) and chronic thyroiditis (2 cases), were studied. All cases of follicular carcinoma and 18 cases (90%) of papillary carcinoma expressed the EGFR immunoreaction in the cytoplasm with a moderate to strong staining intensity. A weak immunoreaction for EGFR was noted in some benign thyroid diseases. CP showed various degrees of positivity in all cases of follicular carcinoma and 19 cases (95%) of papillary carcinoma. The benign thyroid lesions were consistently negative for this antigen, not counting one case of Hurthle cell adenoma. There was a positive correlation between EGFR and CP immunostaining intensity in thyroid carcinomas, representing higher expression of EGFR accompanied by a stronger staining intensity of CP. Except for two cases of papillary carcinoma, all cases showed immunoreaction for TG. The results indicate the enhanced expression of EGFR and CP in thyroid carcinomas. EGFR and CP thus appear to be valuable tools for differential diagnosis between benign and malignant thyroid neoplasms. PMID- 1867099 TI - Paraffin-immunohistochemical analysis of 226 non-Hodgkin's malignant lymphomas in the endemic area of human T-cell leukemia virus type 1. AB - A study was conducted to evaluate the usefulness of paraffin-immunohistochemistry for histopathological classification of non-Hodgkin's malignant lymphomas (NHML). the phenotypes of lymphoma cells and other cells were examined using 11 monoclonal and 3 polyclonal antibodies by the ABC method on paraffin-embedded tissue sections of 226 cases of NHML, comprising 94 B-cell lymphomas (B-ML) and 132 T-cell lymphomas (T-ML). In 219 NHML cases (96.8%), lymphoma cells reacted with more than one of these antibodies. A set of MB-1, Mx-pan B, L26, LN-1, LN-2 and anti-immunoglobulin light chain antibodies characterized each subtype of B MLs, categorized according to the Kiel classification. Mantle-zone lymphoma (MzML) was added as one subtype. L26 stained the largest number of B-MLs (82.8%). B-cell chronic lymphocytic leukemia (B-CLL) was labeled most frequently by MB-1. MzML was characterized by reactivity of lymphoma cells with LN-2 and by the appearance of monoclonal immunoglobulin light chain along the cell membrane. Follicle center cell lymphomas were stained by LN-1 and LN-2, although a small number of proliferating cells were labeled by LN-1 in B-CLL, MzML and the immunocytoma lymphoplasmacytic/cytoid variant. MT-1 and/or UCHL-1 showed various degrees of reactivity with the cell membranes of lymphoma cells in 94.8% of T MLs. Among the T-cell pleomorphic lymphomas of Suchi and Lennert, the adult T cell leukemia/lymphoma type, defined by stippled heterochromatin distribution and peculiar huge cells, reacted selectively (p less than 0.05) with anti phosphokinase C antibody. Anaplastic large cell T-ML reacted with a set of Ber H2, LN-2 and Leu M1. In T-zone lymphomas without hyperplastic follicles, angioimmunoblastic lymphadenopathy with dysproteinemia-type T-ML, lymphoepithelioid cell lymphomas and some pleomorphic lymphomas comprising clear large lymphoma cells, there were many intermingling B cells, and their constitution varied. In some lymphoblastic lymphomas of both the T cell and B cell type, phenotypes of T cells and B cells were expressed. Consequently, it was shown that paraffin immunohistochemistry was useful for the practical histopathological diagnosis of NHML even in the area where human T-cell leukemia virus type 1 is endemic. PMID- 1867101 TI - The heart under normal and pathological conditions: comparative and experimental studies. PMID- 1867100 TI - Peptide tyrosine tyrosine-positive ovarian carcinoid tumor arising from a dermoid cyst. AB - A case of ovarian carcinoid tumor of the trabecular type is presented. The small carcinoid tumor was found incidentally in a resected dermoid cyst. Histologically, the tumor was surrounded by a smooth muscle layer with focal stromal invasion. Non-carcinoid papillary mucosa and a few small glands, simulating the mucosa of the fallopian tube and remnant mullerian glands, respectively, were also present adjacent to the carcinoid tumor and enclosed by the same smooth muscle layer. The tumor cells revealed argyrophilia, and were positive for peptide tyrosine tyrosine (PYY) in the cytoplasm and for CEA in part of the luminal surface. This case was considered to be a rare ovarian carcinoid tumor arising from a dermoid cyst, without association of struma ovarii. PYY may be a potential marker for determining the histogenesis of ovarian carcinoid tumors. PMID- 1867102 TI - Ultrastructural changes at the border of the ischaemic zone within one hour of coronary artery occlusion. AB - The ultrastructure was studied by electron microscopy in myocytes obtained from the periphery of the ischaemic zone 10, 20, 40, and 60 min after occlusion of the left anterior descending coronary artery (LAD) in open chest anaesthetized cats. The morphology of this zone was compared to that of the normally perfused myocardium in the same hearts. Samples were collected from the border of the ischaemic tissue as defined by in vivo injection of fluorescein and verified by regional blood flow measurements with radiolabelled microspheres. After 10 min of LAD-occlusion, we observed swelling of the mitochondria in the border zone. The mitochondrial swelling remained stable for the first hour after LAD-occlusion. There was no difference in the fractional volume of lipid droplets between the normal and border zones after 10 min of ischaemia. The fractional volume of lipid droplets, however, was significantly reduced in the normal zone after 20 min of coronary artery occlusion, whereas it remained unchanged in the border zone. Up to 60 min after LAD-occlusion the fractional volumes of cytoplasm in the border zone were not different from the corresponding values in the normal zone, indicating that there was no cytoplasmic oedema in the border zone. However, a reduced fractional volume of myofibrils in the border zone after 20 min of LAD occlusion, may indicate a slight cell swelling, probably due to the mitochondrial swelling. In the border zone there was a slight increase in the number of cells with sarcolemmal injuries after 10 min of LAD-occlusion. Cells with chromatin clumping and margination were found after 20 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867103 TI - Early restoration of cardiac function in hearts with acute regional ischaemia. The importance of beta-adrenergic stimulation. AB - The effects of acute coronary artery occlusion in anaesthetized cats has been studied with regard to changes in cardiac function and regional myocardial blood flow. Occlusion of the left anterior decending coronary artery (LAD) is followed by a rapid reduction of peak systolic blood pressure (LVSP) and contractility (dP/dt) and increased left ventricular end-diastolic pressure (LVEDP). Five minutes after coronary occlusion heart rate, LVSP, and (dP/dt) was reduced and LVEDP increased. Global cardiac function measured by these variables was gradually restored to preocclusion values; LVSP after 10 min., heart rate and dP/dt after 20 min. After 40 and 60 min these variables were stable at preocclusion levels. LVEDP remained permanently elevated. In hearts with regional ischaemia and paced heart rate global cardiac function was mainly restored 20 min after coronary occlusion except for increased LVEDP, both in cats pretreated with non-selective beta-adrenergic blockade (propranolol) and in unblocked cats. In general, blood flow in non-ischaemic myocardium adjacent to the ischaemic region increased following coronary occlusion, although not significantly in the endocardium. The endocardial/epicardial blood flow ratio was stable in unblocked hearts and was reduced in beta-blocked hearts. In normally perfused myocardium remote from the ischaemic region, blood flow increased following occlusion both in beta-blocked and unblocked cats, most pronounced in the epicardium; the endo/epicardial blood flow ratio decreased. PMID- 1867104 TI - The angina pectoris controversy during the 1920s. AB - This paper examines the evidence for and against the various rival theories for the explanation of pain in angina pectoris. It is shown that the counterarguments used during the 1920s against the coronary theory had not been answered a decade later when the coronary theory was generally accepted by the research and clinical community. PMID- 1867106 TI - Organization of connexons and gap junctions in human heart cells. PMID- 1867105 TI - Effects of low osmolar contrast media on cardiac function: optimal sodium concentration for contractility. AB - The effects of adding NaCl to the non-ionic contrast medium iohexol (Omnipaque) were investigated in the isolated rat heart. Iohexol (150 mgI/ml) with 0, 10, 20, 30, 50, 145 mM NaCl added and the ionic dimeric compound ioxaglate (Hexabrix 160 mgI/ml) containing approximately 75 mM NaCl were examined. Coronary flow rate (CFR), heart rate (HR), left ventricular developed pressure (LVDP) and myocardial high energy phosphate compounds at the end of the experiments were measured. In all groups examined the physiological changes following contrast media injection were only transient and the recovery to normal values of HR and LVDP occurred within 30 seconds. The contractile changes after contrast media exposure were dependent on the concentration of sodium added. The addition of 20 mM sodium to iohexol induced the least changes in LVDP. It is concluded from the present study that addition of sodium in the range of 20-40 mM to non-ionic contrast media, may reduce the immediate cardiac disturbances during coronary angiography. PMID- 1867107 TI - Lipid peroxidation and membrane damage of the heart. AB - Biological membranes separate the cells from the environment and control flow of molecules and information between the cell and its surroundings. In addition, the cellular energy supply is dependent on membrane functions. The present chapter deals with membrane lipid peroxidation and how this process might influence the physiology and pathophysiology of the myocardium. PMID- 1867108 TI - Lipid accumulation in the perfused rat heart after isoproterenol administration. AB - Isoproterenol is a potent lipolytic agent. It has also been shown to induce accumulation of lipid droplets in the myocardium in vivo. The isolated working rat heart model was applied to evaluate the effect in vitro. Twenty-four rats were randomly separated into four experimental groups of six rats, all receiving Krebs-Hensleit buffer with 11mM glucose. The control group had no supplement, the other groups received either 10(-5) M isoproterenol, 1.2 mM palmitate, or a combination of the two. Tissue levels of triglycerides and phospholipids, and the fractional volume of lipid droplets were determined at the end of the 30 min perfusion in the working heart mode. Ventricular function was monitored continuously and showed a marked increase in the isoproterenol treated groups. The level of tissue phospholipids remained unchanged in all groups. Whereas tissue triglycerides were significantly increased in the group receiving only palmitate as compared to the other groups. A corresponding increase was, however, not found to be significant for lipid droplet quantitation. The results are discussed in terms of possible mechanisms for isoproterenol-induced accumulation of neutral lipids in the myocardium. PMID- 1867109 TI - Myocardial contractile performance during acute coronary occlusion with special emphasis on nonoccluded regions. AB - Ischaemia of the left ventricle caused by coronary artery occlusion generally leads to less changes in overall ventricular performance than would be expected from the amount of ischaemic, noncontracting tissue. Ischaemic myocardium shows elongation of segment lengths and paradoxial movement during contraction of the left ventricle. Compensation for the loss of contractile tissue is most likely related to increased performance of the nonischaemic myocardium and the most likely mechanisms involved are discussed. The effect of increased preload, brought about by increased left ventricular end-diastolic pressure following coronary occlusion, on nonischaemic parts appear to be the most important mechanism of compensation. PMID- 1867110 TI - The national mental health programme in the United Republic of Tanzania. A report from WHO and DANIDA. AB - This is the terminal report on the pilot implementation phase of the national mental health programme in the United Republic of Tanzania which was carried out as a cooperative venture between the Government of Tanzania, the Danish International Development Agency (DANIDA), and the World Health Organization (WHO). Although Tanzania had already achieved wide coverage of its population through a decentralized and easily accessible system of primary health care facilities providing the most essential services, its mental health services were poorly staffed and concentrated in a few custodial-type institutions and out patient departments hardly capable of ensuring even one contact per year to about one-fifth of the estimated 100,000 severely mentally ill adults and 37,000 children in need of care at any given point in time. The programme design, developed jointly by the three parties involved, aimed to take full advantage of Tanzania's existing primary health care infrastructure by integrating mental health into the general health services of the country, including the 'grassroot' level of the services in the village and the district. The objectives guiding the new programme were: (i) to create an infrastructure for mental health care provision which should meet the requirements of both adequate population coverage and quality of service; (ii) to raise the community's awareness of mental health issues (including informing the community on the availability of effective means to deal with specific problems) and thus enlist its support and participation. The essential features of the adopted strategy were as follows. 1. Mental health care provision was conceived as a sub-system within the health care system, extending from rural health posts and dispensaries through rural health centres to district and regional hospitals. While full integration of mental health care within the general functions of the health workers was sought at the village and dispensary level (first echelon of care), relative differentiation and identity of mental health services were considered necessary at the district and regional levels (the second echelon). Tasks appropriate to each level of care were defined in operational terms and referral pathways were designated to enable the unobstructed access of the patient to more specialized diagnostic or therapeutic services if the problem was not within the competence of the more peripheral level. These pathways were also used in reverse when, following assessment or treatment, a patient was discharged back to the rural service with appropriate instructions about maintenance treatment and aftercare.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1867111 TI - Tryptophan and its metabolite concentrations in human plasma and breast milk during the perinatal period. AB - Concentrations of tryptophan (free and protein bound) and its metabolites in plasma of maternal vein at delivery, umbilical vein, umbilical artery, neonatal vein and breast milk were determined by high performance liquid chromatography. The plasma levels of tryptophan and most of its metabolites in umbilical vein and artery were significantly higher than those in maternal vein. The concentration of total tryptophan in plasma of neonatal vein showed marked decrease at 24 h after birth in comparison with that at birth, but the total kynurenine concentration was not decreased in plasma of neonatal vein. The colostrum contained a high level of total tryptophan. There were high ratios of free to total tryptophan in colostrum, transitional and mature milk. In the blood, ratios of free to total of tryptophan and kynurenine were kept at constant level throughout the perinatal period. PMID- 1867113 TI - Clonazepam serum levels in epileptic patients determined simply and rapidly by high-performance liquid chromatography using a solid-phase extraction column. AB - We studied the use of high-performance liquid chromatography (HPLC), using a solid phase extraction column (Bond Elut cartridge column), for the simple, rapid and sensitive determination of serum clonazepam levels in epileptic patients. Extracted aliquots were analyzed by HPLC, using a reverse phase ODS column (mu Bondapak C18). The analytical mean recovery of clonazepam added to the blank serum averaged 99.9%. The detection limit was as high as approximately 2 ng/ml in the serum. The reproducibilities were 2.3-8.6 CV % in the within-day assay and 6.5 CV % in the between-day assay, indicating that the analysis method was effective in the determination of clonazepam serum levels. Accordingly, we suggest that the present method, using a solid phase extraction column, may be useful for the routine monitoring of clonazepam serum levels in epileptic patients. PMID- 1867112 TI - Effect of a long-acting somatostatin analogue (SMS 201-995) on a growth hormone and thyroid stimulating hormone-producing pituitary tumor. AB - A 46-year-old woman with acromegaly and hyperthyroidism due to a pituitary adenoma. She had high serum thyroid-stimulating hormone (TSH) levels and very high serum growth hormone (GH) levels. Transsphenoidal removal of the tumor, post operative irradiation, frontal craniotomy for removal of residual tumor and large dose bromocriptine therapy were carried out consecutively. After therapy, serum GH levels gradually decreased, but not to the normal range, and serum TSH levels remained at inappropriately normal levels. Using immunoperoxidase techniques, GH , TSH- and follicle-stimulating hormone (FSH)-containing cells were demonstrated in the adenoma. A long-acting somatostatin analogue (SMS 201-995, 600 micrograms/day) suppressed the serum GH level to the normal range with a concomitant suppression of TSH. Furthermore, the paradoxical serum GH responses to TRH and LH-RH were slightly improved. No important subjective side-effects were noted. Therefore, SMS 201-995 appeared to be a very effective drug in this patient with a GH- and TSH-producing pituitary tumor. PMID- 1867114 TI - Examination of microvascular structures of midcortical region in sheep kidneys: a three dimensional approach. AB - Polyester-crystic cast was observed to reach the peritubular capillary plexus following injection in sheep kidneys. Microvascular structures in this region are also reported in this study. Glomeruli were found to vary in size and shape. Diameters of afferent arterioles were larger than those of efferent arterioles. The glomerulus is supplied by more than one afferent arteriole, and in some regions, the blood in afferent arterioles joins collateral circulation via the intercapillary plexus. Morphological properties at the end of the peritubular capillary plexus were found to be remarkably significant. PMID- 1867115 TI - Automated direct assay system for RU38486, an antiprogesterone-antiglucocorticoid agent, and its metabolites using high performance liquid chromatography. AB - An automated direct assay system using high performance liquid chromatography was developed for the measurement of RU38486 and its three metabolites (RU42698, RU42848, RU42633) in human serum. Serum concentrations of these compounds were measured up to 144 h following single oral administration of 200 (200 mg group, n = 3) or 400 mg (400 mg group, n = 3) of RU38486 to healthy female volunteers. The serum half-lives (200 mg group-400 mg group) of RU38486, RU42698, RU42848 and RU42633 were 31.8-33.1 h, 41.2-39.3 h, 33.9-36.6 h and 29.2-36.6 h, respectively. Our system could quantify them easily and simultaneously, and was considered to be valuable in studies on the relationship between the pharmacokinetics and the clinical effects of RU38486. PMID- 1867116 TI - [The clash of new information technologies]. PMID- 1867117 TI - [The terminal patient and psychotherapeutic approach]. AB - The end stage situation, namely AIDS and malignant diseases, patients are analysed by the authors from the psychiatric and psychologic standpoint. A multidisciplinary clinical approach is pointed out and psychotherapeutic attitude and action parameters are referred to achieve both the understanding of persons in those situations, and the correct clinical praxis towards them. PMID- 1867118 TI - [Prevalence of HIV1 and HIV2 infection in women living in an area of Lisboa City]. AB - A seroprevalence study of HIV1 and HIV2 infection in women attending a Family Planning and an Antenatal Clinic was done in an area of the city of Lisbon where 7% of the population is of African origin. The protocol of study was of non linked type although with the possibility of collecting a second sample of blood for confirmation of results. Epidemiological, social and clinical data were collected from 1390 women and this was followed by the collection of a blood sample for the seroepidemiological study of HIV1 and HIV2. The population that was submitted to blood tests (75%) was compared to the one that missed the test and it was found that no important differences were present between the two. The criteria for HIV1 or HIV2 positive results were the presence of a positive ELISA test confirmed by an Western Blot revealing antibodies against the three proteins env, core and gag. For a test to be considered positive results by both methods had to be found in a second sample collected later. The prevalences of infection were of 0.29% for HIV1 and 0.29% for HIV2 although the prevalence of HIV2 in the population of African origin was higher (1.45%). The six seropositive cases detected included a drug addict, one prostitute, one case of African origin and two cases with multiple sexual partners. The clinical, epidemiological and immunological features of the seropositive cases are presented and the prevalence found is discussed in the context of other portuguese data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867119 TI - [Application of aspiration cytology in the diagnosis of tumor lesions in children]. AB - Fine needle aspiration cytology (FNAC) became increasingly popular for evaluating of both superficial and deep seated lesions, but its use in children has been limited. We report our recent experience with FNAC in the pediatric group. The study population included 34 males and 12 females and the age ranged between 11 months to 16 years. The aspirated sites were: testis (n = 14), lymph node (n = 12), bone (n = 9), pelvis (n = 2), retroperitoneum (n = 1), soft tissue (n = 6), lung (n = 1) and orbit (n = 1). The aims of FNAC were to diagnose a primary lesion (25 cases) and to document relapse of neoplastic disease (21 cases). Of the 46 aspirates, 28 were diagnosed as malignant, 4 as benign, 2 were inconclusive; in the remaining case the material was considered inadequate. Eleven out of 14 testicular cases were normal. FNAC diagnosis was confirmed either by histology (25 cases) or by the clinical evolution (18 cases). We conclude that FNAC can be considered a major diagnostic tool for the characterization of the tumoral lesions in childhood, both for diagnostic purposes and for evaluation of the progression of neoplasia. It may also provide useful information for guiding the therapeutical strategy. PMID- 1867121 TI - Behcet's disease in Portugal. AB - During the last decades 156 patients with Behcet's disease were diagnosed and studied in Portugal. Until 1966 only two cases were referred in Portugal. In 1978 we reported 23 cases (18 males and 5 females) with multisystemic involvement, not different from that reported in other publications elsewhere. In 1987, 17 cases were reported from the Oporto region, diagnosed during a period of 5 years. In the region of Coimbra 15 cases were diagnosed (6 males and 9 females). In the Lisbon area from 1969 until 1990, 123 cases were studied altogether, 76 during the last decade (35 males and 41 females). All the cases studied had oral ulcerations and a high incidence of ocular involvement (clinical and sub clinical, 87%). HLA-B5 was detected in 50% of the patients. At least four cases were fatal, three died with neuro-Behcet. Steroids, colchicine and thalidomide were the main form of treatment, for the patients in the Lisbon area, but in some cases chlorambucil, cyclophosphamide, azathioprine, cyclosporine-A, fibrinolytic therapy, plasmapheresis and isovolemic hemodilution were also used. PMID- 1867120 TI - [Beneficial effects of added glicazide in patients with type II diabetes mellitus treated with insulin]. AB - The aim of the study was to assess, in patients with non insulin dependent diabetes mellitus (NIDDM), either with previous failure to sulphonylureas or insulin treated since the disease started, if the combination of gliclazide to insulin therapy might induce a reduction of daily insulin requirement. 30 caucasian type II patients used to self-monitoring (11 female, 19 male, mean age 55.78 +/- 8.07) with residual pancreatic function (glucagon induced C-peptide release = 1.01 +/- 0.70 microgram/ml) entered the study. 8 were excluded for non compliance or for high antiinsulin antibodies levels and 4 are still under study. Each patients was given, for 3 months, 240 mg of gliclazide in addition to usual daily dose of insulin. Data presented as mean +/- s.e.m. were analysed with analysis of variance (p less than 0.05). Mean initial values of main parameters were as follows: glycaemia 192.7 +/- 33.1 mg/100 ml, insulinaemia 9.5 +/- 4.5 microUI/ml, daily insulin requirements 33.11 +/- 10.47 U/d, HbA1 C 7.5 +/- 1.7%. Total cholesterol 240.1 +/- 52.2 mg/10 ml, triglycerides 120.6 +/- 60.3 mg/100 ml. After 3 months treatment significant reduction in mean daily insulin requirements (20.78 +/- 16.15 U/d) was observed. In 13 patients (72.2%) while keeping good metabolic control (HbA1 C 7.46 +/- 1.63), insulin therapy was reduced (9 patients) or even stopped (4 patients). In the other 5, insulin was maintained or slightly increased. The increase in glucagon induced C-peptide release (1.41 +/- 0.99 micrograms/ml) did not reach significance, while glycaemia and insulinaemia were not changed (196.0 +/- 34.1 mg/100 ml, 11.02 +/- 5.05 microUI/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867122 TI - [Chronic hypoparathyroidism: review of 5 clinical cases]. AB - In 5 patients with a long clinical evolution of tetany and/or convulsions and with documented hypocalcaemia and hyperphosphatemia, low or inappropriate values of parathormone were detected. Only two of the patients had a history of subtotal thyroidectomy and all presented with basal ganglia calcification, bilateral subcapsular cataracts and prolonged QTc interval in the ECG. After one month of oral therapy with calcium and calcitriol, the values of calcaemia and phosphatemia were in a near-normal range with the exception of a patient in which that normalization was much slower and only occurred after correction of magnesaemia. In this last patient statistical correlation between QTc interval in the ECG and the calcaemia was statistically significant (P less than 0.001). We conclude that the QTc interval can be a useful and accessible index in acute situations of symptomatic hypocalcaemia. PMID- 1867124 TI - [Epidermolysis bullosa and dermo-epidermic junction. Clinico-pathologic correlation]. AB - Epidermolysis bullosa encompasses a group of hereditary diseases clinically and pathologically characteristic. In this review the grouping criteria commonly accepted for their classification are described. The cleavage phenomena observed in these diseases are analysed in accordance with the concept of a skin area including dermal and epidermal interrelated structures--the dermo-epidermal junction zone. Finally in the most expressive forms the clinical manifestations, diagnosis and treatment are reviewed. PMID- 1867123 TI - Herpes zoster and controlateral hemiplegia in an African patient infected with HIV-1. AB - One of the neurologic complications of human immunodeficiency virus infection are cerebrovascular accidents. In HIV infected patients, ischemic strokes have been reported secondary to nonbacterial thrombotic endocarditis and cerebral arteritis. We describe an unusual cause of stroke in HIV-1 infection: Herpes Zoster ophtalmicus with contralateral hemiplegia. PMID- 1867126 TI - Pyridoxine neuropathy. A four-year electrophysiological and clinical follow-up of a severe case. AB - In a 54-year-old male a severe sensory neuropathy was observed during treatment for pulmonary tuberculosis with isoniazid (400 mg/day) and pyridoxine (600 mg/day). Eight months after withdrawal from isoniazid the sensory symptomatology was still progressing, although muscle strength was never reduced. A sural nerve biopsy revealed marked loss of large myelinated fibres. Only when pyridoxine treatment was interrupted did a slow improvement begin. A clinical and electrophysiologic follow-up showed a very slow and still incomplete recovery after four years. The possibility of an unusual individual susceptibility to toxic effects of pyridoxine is considered. PMID- 1867125 TI - A clinical and neurophysiological trial on nootropic drugs in patients with mental decline. AB - The different expressions of mental decline in elderly people, from simple senile benign forgetfulness to SDAT, can be evaluated by psychometric and neurophysiological tests. In the present study, the effects of oxiracetam, piracetam and placebo were compared in a group of elderly subjects. The results of the trial, structured as single blind, clearly showed that nootropics positively effect both clinical and neurophysiological performances and that oxiracetam produces a more pronounced effect when compared to piracetam. In fact, oxiracetam was found more effective in improving psychometric scales such as GDS (clinical performances) as well as the amplitude and the latency of the P300 (neurophysiological performances), which reflect a functional recovery of the cerebral pathways related to attention and memory. PMID- 1867127 TI - Archaic reflexes in normal elderly people. AB - The AA. have considered the incidence of some primitive reflexes in the "normal" old people. 120 subjects have been examined (60 M and 60 F) between the 70 to 90 age-group. The patients have been selected on the basis of the absence of neurologic disorders, psychiatric and systematic or dysmetabolic diseases. All the subjects undergo a standard neurologic examination. Results show that the examined reflexes can be present in normal old people. These signs seem to be related to the physiological ageing of the nervous system. PMID- 1867128 TI - MRI findings in a patient with a familial form of motor neuron disease. AB - The authors report the case of a 32-year-old woman who developed symptoms and signs possible manifestations of a familial motor neuron disease with left sided pyramidal signs and marked wasting and weakness in the ipsilateral upper girdle, progressively extended to the contralateral upper limb. The CT-scan showed only frontal cortical atrophy. MRI disclosed a restricted area of increased signal intensity in the centrum semiovale of the subcortical white matter of the right prefrontal cortex. This young woman did not disclose any risk factors for cerebrovascular diseases nor other disorders of the CNS; therefore the authors are of the opinion that the white matter changes observed on MRI are not occasional findings, but are related to the pathologic process occurring in consequence of her neurodegenerative disorder (possible ALS). PMID- 1867130 TI - [Memory. Cognitive, anatomic and pathologic models]. AB - This overview deals with the neuropsychology of memory. First cognitive models proposed for primary and secondary memory are reported, particularly the working memory theory and episodic/semantic distinction are discussed. Briefly the modern point of view about the anatomical bases of memory functions are reported with stressing above all the role of limbic structures. Lastly the pathology of both primary and secondary memory is dealt with, trying to abstract the clinical features of different syndromes. PMID- 1867129 TI - Different biological properties of paired HIV-1 isolates from peripheral blood mononuclear cells and cerebrospinal fluid. AB - Seven paired HIV-1 isolates from peripheral blood mononuclear cells (PMCs) and cerebrospinal fluid (CSF) of infected subjects at various stages of the disease were studied for their capacity to replicate in continuous cell lines (Molt-3 and U-937 cells) and to induce cytopathic effects "in vitro". Obtained results indicate that paired HIV-1 isolates from PMCs and CSF of the same patient can differ in their replicative activity "in vitro", suggesting that, at least in some cases, CSF isolates may represent a distinct subtype of HIV-1. PMID- 1867131 TI - [Predictive value of the Zung scale in geriatric depression]. PMID- 1867132 TI - [The "Sickness Impact Profile" questionnaire (SIP): Spanish version of a measure of health status]. AB - The objective of this paper is to present the results of the translation and adaptation into Spanish of a questionnaire (The Sickness Impact Profile --SIP--) for measuring the physical and psychosocial dysfunctions generated by a disease. For this the SIP, together with some clinical measures of physical and psychosocial status were administered to a series of 50 patients afflicted by multiple sclerosis. We found not only that the SIP could be considered a good instrument for measuring the physical and psychosocial impact of illness, but also that it is adequate to differentiate in it a physical and a psychosocial dimensions. PMID- 1867133 TI - [Co-morbidity of affective disorders and personality disorders]. AB - The present study intends to investigate selected factors related to comorbidity of affective and personality disorders. The authors studied a group of in patients from the Psychiatric Unit of the Hospital de Clinicas de Porto Alegre, who were hospitalized during 1985 to 1989. The factors selected were: age, gender, level of education, marital status, age at the beginning of the affective disorder, number of previous hospitalizations, suicide attempts, drug abuse and length of hospitalization. A non-paired case-control study was performed. The results of this study revealed that patients with comorbidity tended to be companionless, to have more suicide attempts and to show unipolar affective disorder. These factors yielded statistical significance. The remainder of the factors that were studied did not convey any statistical significance. PMID- 1867134 TI - [Treatment of affective disorders with clonazepam]. AB - On the basis of the hypothetical utility of clonazepam (CLN) for the treatment of affective disorders, by means of previous references and etiopathogenic hypothesis like the Kindling phenomenon we have been developing a study in order to evaluate that usefulness and efficacy which, includes 32 patients with affective disorders; 23 of them with a diagnosis of bipolar disorder (manic) the greatest part of the subjects had been previously treated with lithium antidepressants or neuroleptics, and clonazepam was introduced because of an inadequate response, treatment intolerance or searching for a specific effect. Our results suggest a prevalence of partial and good responses (85%) The same in the objective evaluations as in the subjective ones being the levels of response higher than in previous treatments. The study supports the use of CLN in the treatment of patients who suffer from affective disorders, particularly in hypomanic episodes. PMID- 1867136 TI - [Kinesio therapy in maxillofacial practice]. AB - The importance taken on by Maxillo-Facial kinesitherapy and the constant increase of its application possibilities have led to increased mention of this new treatment. Its efficacy is obvious, it should no longer be ignored by physicians, surgeons and specialists in the oro-cervico-facial field. Hardly explored twenty years ago, this field today constitutes a new discipline. The patients should now to benefit from this therapy, in order to ensure a total recovery of their functions following a traumatising pathology or the onset of a TMJ syndrome. PMID- 1867135 TI - [Comparative analysis of a population hospitalized for alcohol "dependence" and "abuse" with other similar alcoholic populations: a study of 1,300 patients]. AB - The authors refer on introduction to a former research where they describe results from 150 inpatients diagnosed of "Alcohol Dependence" and "Alcohol Abuse Syndromes" admitted during 1980-1984 at the Psychiatry Department of University Hospital of Valladolid. A comparison of epidemiologic, clinic, diagnostic and care patients patterns is made versus three other studies , where similar groups of alcoholic patients are studied through 47 variables. The first investigation reports findings from 613 alcoholic out patients demanding psychiatric care at University Hospital in Valladolid. The second one study 134 alcoholic patients (70% outpatients and 30% inpatients) at the Hospital General in Burgos. The last one reports finding from 403 alcoholic inpatients at the Psychiatric Service of "Ramon y Cajal" Hospital of Madrid. A group of 130 patients are studied as a whole, 1,127 males (86.89%) and 173 females (13.3%). Fifty per cent of the sample (n = 653) were inpatients and the remainder were outpatients; 28.30% (n = 368) were diagnosed by means of CIE-8a; 61.38% (n = 798) by means of CIE-9a; and 10.30 by DSM-III diagnostic criteria. The variables evaluated were population, age, sex, civil state, place of birth, place of living, level of education, profession, work capability, economical status and current social class, working and marriage adaptation, place composition, first work age, emigration, family psychiatric problems, affective deprivation, personal background, former treatment for drinking problems, start of drinking average age, abuse average time, kind of drinking, drinking day average amount, motive of abuse increments, consultation motive, somatic and psychiatric diagnoses, others drugs consultations, TAC and EEG results, first pharmacologic treatment, inpatient average time, and later hospitalizations. A table, a graphic and 83 bibliographic quotations, part of which belong to a former work, are included. PMID- 1867137 TI - [Localization of the mandibular canal: experimental comparison of four types of radiological examination]. AB - This investigation, involves eight dry mandibles, and compares four of radiological examinations to allow the measurement of the depth of the mandibular canal in relation to the alveolar crest. It showed that their (ability to detect the mandibular canal) differed significantly: coronal tomography: 64% retro alveolar X-ray: 83% orthopantomography: 85% coronal tomodensitometry: 100% The retro-alveolar X-ray appears to have the best cost/information ratio, while the coronal tomography must be left aside. PMID- 1867138 TI - [Prosthetic rehabilitation of a case of total amelogenesis imperfecta]. AB - A young adolescent girl suffering from Amelogenesis imperfecta was examined. The treatment plan: teeth kept vital, preparation of provisional resin crowns and their replacement by definitive single crowns. Thus re-establishing aesthetics and function, and furthermore the possibility of giving this young patient the pleasure of finally being able to smile, no longer hiding her teeth. PMID- 1867139 TI - [Malignant melanoma of the oral mucosa]. AB - The oral cavity is a mave "localisation" for the malignant melanoma's development. Surgical excision with a wide margin is the treatment of choice for localized oral melanoma. The prognosis is particularly poor when metastasis occurs. One case is reported, in a alveolar site. PMID- 1867140 TI - [Arsenical necrosis still exists... I have seen it]. AB - Arsenic necroses occur after the use of arsenic anhydride for pulp removal. This technique was widely used until relatively recently. It is interesting to compare, in this regard, the evolution of concepts in this field. PMID- 1867142 TI - [Removable dentures for children in daily practice: for whom and why?]. PMID- 1867141 TI - [Cranio-maxillo-facial fibrous dysplasia]. AB - The fibrous dysplasia of the bones is a big disease, but it has to be considered as an expansive process with local malignancy in the cranio-maxillo-facial localizations. After a review of the literature, 7 cases of fibrous dysplasia are presented. The only curative treatment is surgical, generally mutilating, it has to be completed by a restoring intervention in same time. The abstention and the modeling surgery can be indicated exceptionally, it requires a regular X ray examination, and a clinical follow-up. PMID- 1867143 TI - Facilitating friendship formation in late life: puzzles and challenges. AB - Considerable evidence indicates that friendships contribute to the psychological well-being of older adults. Seeking ways to help lonely older adults form new friendships thus makes a good deal of sense, but as the disappointing results reported by Heller et al. (1991) indicate, translating this conceptually sound goal into a practical reality presents many challenges. This commentary seeks to build upon the authors' analysis of factors that may have undermined the success of their intervention by discussing the social contexts that may be most conducive to friendship formation in late life and by considering whether kin ties represent a more viable focus of intervention efforts than do peer ties. PMID- 1867144 TI - Conservation of resources in community intervention. AB - Evaluated the applications of principles of resource conservation and management in community interventions and compared these to a more individual, perception based psychological perspective. Conservation of resource theory suggests that promotion of well-being and prevention of disease depend on the availability and successful management of resources. When resources are lacking, lost, or when invested without consequent gain, people become vulnerable to psychological and physical disorder and debilitated functioning. Resources, in this context, are defined as those things people value or those things that may help people obtain that which they value. Conservation of resource theory further suggests that resources are to a large extent common to all people, more common within a given culture and time in the developmental cycle, and only to a small extent idiographic. Further, conservation of resource theory posits that resources operate within an ecological context where feedback, sharing, and exchange operate between the individual, social context, and environment. Given these principles, it is reasoned that community interventions must acknowledge the solid base of most problems and accept that interventions must target resources and be intensive enough to change the ecology in which resources operate. PMID- 1867145 TI - Peer telephone dyads: putting conclusions on hold. AB - Commentary on Heller et al.'s (1991) peer telephone intervention for elderly women addresses three issues: (a) the sources and kinds of information needed to inform decisions about the choice of intervention; (b) the criteria used to evaluate the process and outcomes of support interventions; (c) the social psychological dynamics stimulated by the intervention protocol and by the particular form of the intervention. The latter two issues complicate interpretation of the study's findings and raise additional questions about whether and why the intervention was unsuccessful. PMID- 1867146 TI - Social support interventions and the third law of ecology. AB - Most of what we know about the effectiveness of social support is based on field studies of naturalistic relationships and transactions. Social support interventions, particularly those that attempt to create new support providers, stretch the limits of our knowledge base. The article by Heller et al. (1991) highlights gaps in our knowledge, suggests the importance of intimacy in support exchanges, and identifies possible limitations in trying to compensate for deficiencies in family support with new friendships. PMID- 1867147 TI - Support interventions for older adults: confidante relationships, perceived family support, and meaningful role activity. AB - The rationale and problems encountered in implementing a peer-support telephone intervention are described. The research conducted by Heller, Thompson, Trueba, Hogg, and Vlachos-Weber (1991) was based on epidemiological literature documenting the moral enhancing value of confidante relationships. However, that literature may be insufficiently precise to form the basis for an intervention without prior ethnographic study of the local target population. Furthermore, the positive effects of peer friendships may refer to long established relationships rather than to newly formed social ties. It is concluded that future support intervention research with older adults should concentrate on reinforcing meaningful role activities, and that greater attention should be given to strengthening indigenous ties before attempting to create new ones. While prior process research and formative evaluation are of value, we also emphasize the importance of well-controlled field studies in the ultimate test of intervention hypotheses. PMID- 1867148 TI - Setting phenotypes in a mutual help organization: expanding behavior setting theory. AB - Expands Barker's theory of behavior settings by proposing an additional method of classifying settings based on their functional/behavioral aspects--the setting phenotype. Although behavior setting theory has been widely hailed as a revolutionary contribution to behavioral science, it has had limited impact on general psychology. This may be due in part to a reliance on a purely structural method of classifying behavior settings--the setting genotype. Behavioral data were collected from 510 meetings of 13 self-help groups from a mutual help organization for persons with problems in living. A cluster analysis was performed to uncover meaningful behavioral patterns among the groups. Four phenotypes were identified: personal, impersonal, small talk, and advising. Mutual help group phenotype was found to be related to a set of setting characteristics as well as to overall rated change of group members. The results are discussed in light of the significance of the phenotype construct for making behavior setting theory more relevant for social scientists. PMID- 1867149 TI - Community Intervention Trial for Smoking Cessation (COMMIT): opportunities for community psychologists in chronic disease prevention. AB - Opportunities for participation in chronic disease prevention programs are discussed in the context of a description and analysis of the National Cancer Institute's Community Intervention Trial for Smoking Cessation (COMMIT). COMMIT involves 11 matched pairs of communities with random assignment to the intervention condition within each pair. The 4-year intervention is guided by a partly standardized protocol and embodies a number of community psychology principles. The relative congruence of COMMIT with community psychology principles and methods is discussed with particular emphasis on Kelly's (1988) model of community research. Community psychology's participation in chronic disease prevention trials requires understanding of the programmatic framework of National Institutes of Health prevention research and recognition of the constraints imposed by the framework on community psychology practices. PMID- 1867150 TI - Assertive community treatment: correcting some misconceptions. AB - Discusses historical, policy, and research perspectives on assertive community treatment (ACT) and their relationship to 5 commentaries accompanying our recent article (Bond et al., 1990). Collectively, the commentaries focused on self-help groups, missing the point of the study. Further, the commentaries contained several misconceptions centering on a confusion between deliberate sampling based on policy-driven considerations and self-selection into voluntary organizations. In the time since the Stein and Test (1980) demonstration, programs based on ACT principles have become one of the dominant approaches to community mental health services, especially for consumers who do not readily use office-based treatment. The research foundation is robust and is rapidly evolving. Some community psychologists may be responding to outdated and inaccurate stereotypes of mental health services. PMID- 1867152 TI - Comments on Heller, Thompson, Trueba, Hogg, and Vlachos-Weber, "peer support telephone dyads for elderly women". AB - Comments on the support intervention study with elderly women by Heller et al. (1991). The study highlights the need to determine what aspects of social support are most effective for particular populations. I discuss what basic research on supportive functions suggests for this population, and what kinds of knowledge are needed to best translate epidemiologic findings into intervention research designs. Related research on the effects of family vs. peer support is discussed, and processes that may help or hinder family support are proposed. Finally, I note some implications for further research on social networks of elderly persons, and approaches to increasing social companionship and social integration. PMID- 1867151 TI - Peer support telephone dyads for elderly women: was this the wrong intervention? AB - Tested a preventive intervention in which peer telephone dyads were developed for low-income, community-living, elderly women with low perceived social support. After an initial assessment, respondents were randomly assigned to either an assessment-only control or received 10 weeks of friendly staff telephone contact. After a second assessment, participants receiving the staff contact were randomly assigned to continue that contact or were paired in dyads to continue phone contact with one another. Dependent variables were measures of perceived social support, morale, depression, and loneliness. All groups, particularly the staff contact group, showed some improvement in mental health scores over time, but there were no significant differences between intervention groups, or between intervention and assessment-only control groups. The results suggest that participation in the study and in personal assessment interviews at home were probably morale enhancing, and that additional telephone contact did not significantly add to that effect. Evidence also indicates that, in this sample, low perceived family support was significantly related to poor mental health, so it is possible that a program designed to increase friend support may have been the wrong intervention. PMID- 1867153 TI - Let's hang up and try again: lessons learned from a social support intervention. AB - A support intervention by Heller et al. (1991) sought to improve the well-being of elderly women by providing friendly telephone contact with staff or peers. The failure of this thoughtful and carefully implemented intervention serves to highlight the difficulty of designing support interventions. Several lessons are discussed regarding the complexity of the support process, the utility of different research strategies, the importance of specifying the targeted focal point in the support process, the need to state models explicitly, the choice of measures, and the implications of select participant samples. PMID- 1867154 TI - Peer support telephone dyads for elderly women: the wrong intervention or the wrong research? AB - Reaction to the intervention paper by Heller et al. (1990) places their work into a larger framework of social support interventions to make explicit the assumptions underlying the project. It is suggested that the intervention was constrained by the experimental design of the evaluation research and overlooked important features in the process of relationship development among dyads. In developing interventions designed to impact personal relationships, it is recommended that community psychologists (a) consider the context in which personal relationships are formed, maintained, and terminated; (b) use the power of their scientific inquiry to create, strengthen, or legitimize new social roles for people who are disenfranchised; (c) promote the use and legitimacy of research methods that compliment rather than dictate the nature of interventions. PMID- 1867155 TI - Fine-tuning theory to the needs of the world: responding to Heller et al. AB - Comments on the Heller et al. telephone intervention with isolated elderly women are presented. The importance of addressing contextual factors involved in assessments of social support in community samples is discussed. Comparisons are drawn between the assessment of social support among an elderly sample and an assessment of social support among a sample of chronic illness patients. Three key issues are discussed: (a) Is a little support better than no support and is a little all we really need? (b) Is family support more important than friend support, at least to this population? (c) Can long-term relationships be replaced? PMID- 1867156 TI - The 1990 Society for Community Research and Action Award for Distinguished Contributions to Community Psychology and Community Mental Health: Edward Seidman. PMID- 1867157 TI - Growing up the hard way: pathways of urban adolescents. AB - Presented a description and initial findings from the Adolescent Pathways Project (APP). There is a dearth of developmentally and ecologically anchored knowledge concerning adolescents, particularly poor and ethnically diverse urban adolescents, other than that they are at greater risk for behavioral, emotional, and educational problems. As a result, our ability to develop and implement grounded prevention programs is severely limited. The APP was intended to fill this knowledge gap. Using an accelerated longitudinal design, the APP examines the developmental trajectories of an ethnically diverse sample of 1,333 black, Latino, and white youth from inner-city public schools in Baltimore, Washington, DC, and New York. It involves four interrelated studies: Youth, Parent, School, and Neighborhood. The project's major aim is to identify the critical psychological, developmental, and ecological factors that facilitate positive as well as negative outcomes. This initial description of the APP presents the overarching ecological-developmental framework and guiding questions, as well as initial findings central to the tenets of community psychology. PMID- 1867158 TI - Means-ends problem-solving skills, life stress, and social support as mediators of adjustment in the normative transition to high school. AB - Examined the transition of adolescents from middle school to high school through a longitudinal research design. Consistent with other studies, results indicate that the transition is associated with declines in grade point average and attendance, and that these changes persist or worsen over the course of the freshman year. Life stress and social support from family, friends, and school personnel each showed expected relationships with some outcome variables, though these varied in pattern and magnitude. Furthermore, there was some indication that these sources could be used in multivariate analyses in assessing their relationship to outcomes. Finally, means-ends problem-solving skills did not predict levels of posttransition support. Results are seen as supporting a differential model of the role of individual and environmental resources in the high school transition, especially with regard to the negative changes in grades and attendance and the pattern of correlations between social support sources and outcomes. PMID- 1867159 TI - Expansion strategies of a mutual help organization. AB - Described a study of the expansion strategies of a successful self- and mutual help organization for persons with mental illness. Resource mobilization and behavior-setting theories were used as conceptual frameworks to guide the investigation. Collaborative methods and a grounded theory approach were used. Archives, reports of contacts outside of the organization, and naturalistic observations were data sources. Of particular interest are the processes used by the organization to mobilize internal and external resources and to start new mutual help groups. Results suggest that the organization mobilizes resources from a variety of sources, displays flexibility in securing resources and defining organizational roles, and creates underpopulated settings to encourage individual involvement. The strategies appear to avoid overtaxing resource pools, reduce role ambiguity, and encourage pluralistic participation. Discussion includes several potential explanations for the successful growth of the organization. PMID- 1867160 TI - Psychological frailness and strength in an AIDS-affected community: a study of seropositive gay men and voluntary caregivers. AB - Addressed both the psychological frailness and strength in an AIDS-affected community. The gay community in Sydney, Australia, was represented by men who were seropositive (n = 60) and voluntary caregivers (n = 60). They were compared with two samples of men outside the gay community, who were ill with non-AIDS related medical conditions (n = 30), and well (n = 30). Their psychological frailness and strength were measured by content analysis scales. Both the seropositive men and the caregivers showed the frailness of anxiety, indirectly expressed anger and helplessness, but also the compensating strength of greater personal competence and good feeling relative to the other men. The men who were seropositive or had other illnesses showed the predicted frailness of anxiety and depression but neither indirectly expressed anger nor helplessness. The seropositive men and caregivers of the gay community differed from each other only in the high levels of depression of the former. PMID- 1867161 TI - An evaluation of temporomandibular joints and jaw muscles after orthodontic treatment involving premolar extractions. AB - Experimental subjects (n = 29) were patients who had undergone orthodontic treatment in combination with extraction of maxillary or mandibular premolar teeth, or both. Control subjects (n = 29) were healthy dental students with no orthodontic or extraction experience. Sagittal (corrected axis) tomograms of the TMJs were used to determine the narrowest linear distances between the anterior and posterior outlines of the TMJ condyle and the TMJ fossa, expressed as the joint space ratio. There were no significant (p greater than 0.05) differences between the control and experimental ratios. Bipolar surface electromyograms of the masseter and anterior temporalis muscles were used to determine the isometric contraction velocities of these muscles until 50% and 100% voluntary isometric contraction effort (teeth clenching) was achieved. There were no significant (p greater than 0.05) differences between the control and experimental subjects. Electromyograms were also used to determine the relative contribution of the masseter and anterior temporalis muscles to the bite force developed during brief maximum voluntary tooth clenching, expressed as the activity index. There were no significant (p greater than 0.05) differences between the control and experimental subjects. PMID- 1867162 TI - A radiographic study of condyle position at various depths of cut in dry skulls with axially corrected lateral tomograms. AB - Fifty dry skulls were evaluated by means of submental vertex radiographs and axially corrected tomograms. The condyles were classified into four groups according to anterior surface and shape as viewed on the submentovertex radiograph. Thirty condyles were classified as having a flat anterior surface, 27 as convex, 19 as concave, and 24 as triangular. The analysis of variance for the depth of cut demonstrated (1) no statistically significant difference between the condyle/fossa relationship at the various depths of cut for the convex, flat, and triangular condyles and (2) a statistically significant difference between the condyle/fossa relationship of the concave condyles. The difference was significant at the p = 0.107 level for the anterior joint space (A), and at the p = 0.0671 level for the posterior joint space (B). The analysis of variance, in regard to the subject variable, demonstrated a statistically significant difference at the p = 0.0001 level for all condyles. PMID- 1867163 TI - Remodeling of canines to the shape of lateral incisors by grinding: a long-term clinical and radiographic evaluation. AB - A long-term clinical and radiographic follow-up study was performed after extensive remodeling of the permanent teeth of 26 adolescent patients. The canines were ground to the shape of lateral incisors as part of the orthodontic treatment, and the patients were recalled after 10 to 15 years for clinical examinations. Grinding had been performed either unilaterally or bilaterally on 37 teeth. Unground canines or adjacent teeth served as control or reference teeth. Standardized intraoral radiographs were taken with a paralleling technique. Enamel surface replicas produced by epoxy resin in silicone impressions of the ground teeth were studied by stereomicroscopy. The long-term results were favorable. No significant color differences were observed in 36 of the 37 ground canines. Only one tooth displayed a generalized yellowish discoloration, probably the result of extensive pulp obliteration. There were no significant differences between ground and unground teeth with regard to mobility, reaction to percussion, or temperature sensitivity. Electric pulp testing revealed no statistically significant differences between test and control teeth. Radiographic changes were evident in two of the 37 ground canines. One tooth showed marked obliteration of the crown pulp, and in another tooth the pulp obliteration was almost complete. In the remaining 35 teeth no apparent differences were noted between the ground and unground teeth. In the stereomicroscope two of the ground labial surfaces showed evidence of scratches and grooves produced by the diamond instrument after more than 10 years' observation, but in all other instances the ground surfaces were indistinguishable from normal adult enamel surfaces. In conclusion, the present study has demonstrated that extensive cuspal, labial, lingual, and interproximal recontouring by the grinding of young teeth associated with orthodontic treatment can be performed without discomfort to the patients and with only minor or no long-term clinical and radiographic reactions. PMID- 1867164 TI - Landmarks in three dimensions: reconstruction from cephalograms versus direct observation. AB - A method for generating three-dimensional landmark locations from routine biplane pairs of cephalograms was previously introduced. In this article we compare the locations thus reconstructed to the same configurations as directly recorded through a redundant network of interpoint distances measured with calipers. Six mandibular landmarks were located by both methods on each of 10 dry skulls. With the caliper distances is associated a standard error that can be estimated without explicit remeasurement by the method of "adjustment of networks" familiar from surveying. These standard errors are consistent with the remeasurement error both of the caliper measurements and of the stereolocation from cephalograms; the methods appear to have the same precision, about 0.4 mm per distance. The bias (systematic shift) of the biplane reconstructions with respect to the points used for laying down the calipers may be estimated by regressions of distance discrepancies on the direction cosines of the separations between pairs of landmarks. The caliper tips placed condylion approximately 10 mm medially and a bit forward of where we chose to reconstruct it from biplane cephalograms. The caliper locations of gonion average about 1.6 mm back of their cephalometric position, while those at menton and lower incisal edge are forward by some 1.4 mm. We conclude that the biplane reconstruction (the "three-dimensional cephalogram") is sufficiently accurate for routine clinical and surgical application. PMID- 1867165 TI - A comparative study of stability after mandibular advancement surgery. AB - The postsurgical stability of two groups of patients treated with different fixation techniques after mandibular advancement was evaluated retrospectively. Sixteen patients (group 1) underwent rigid osseous fixation, and another group of 16 patients (group 2) underwent intraosseous wiring fixation. Our findings suggested that skeletal and dental changes occurred in both groups as a result of adaptation to the altered functional equilibrium. Relapse resulting in a percentage loss of the initial advancement occurred primarily 6 to 8 weeks postsurgically. No statistically significant difference was found to exist in the short-term and long-term rates between the two groups. For the population studied, relative stability after mandibular advancement surgery was affected more by individual variability than by the fixation technique. PMID- 1867166 TI - A clinical evaluation of temporomandibular joint disk plication surgery. AB - Clinical and radiographic examinations were performed preoperatively and an average of 18 1/2 months postoperatively on 33 patients who had undergone TMJ disk plication surgery because of significant TMJ dysfunction symptoms that had not been resolved by previous conservative therapy. The results indicated that the disk plication procedure reduced the overall frequency of symptoms by 75%. The frequency of TMJ intracapsular, otologic, and head and shoulder symptoms was reduced by more than 80% after surgery whereas dental symptoms such as bruxing and clenching showed only a 28% reduction in incidence. Of the sample 77% were either free of pain or experiencing only mild symptoms at their postoperative recall, with only nine joints still experiencing moderate or severe symptoms, compared with the 31 joints that were in this category before surgery. PMID- 1867167 TI - Effect of a fluoridated etching gel on enamel morphology and shear bond strength of orthodontic brackets. AB - The purpose of this study was to compare the enamel morphology and shear bond strengths of orthodontic brackets bonded to enamel etched with a fluoridated or a nonfluoridated phosphoric acid gel. Ten extracted third molars were used for the enamel morphology evaluation. The buccal surfaces were divided in two sections separated by an occlusogingival groove. One side was etched for 60 seconds with a 38% phosphoric acid gel, and the other side was etched with a 60% phosphoric acid gel containing 0.5% sodium fluoride. The specimens were then examined with a scanning electron microscope. For the shear bond strength tests, 30 extracted third molars were used. The buccal enamel surfaces of the mesial cusp were used, and the teeth were randomly divided into two groups of 15 teeth each--group 1, 38% phosphoric acid gel for 60 seconds; group 2, 60% phosphoric acid gel with 0.5% sodium fluoride for 60 seconds. Orthodontic lingual buttons were bonded to the etched surfaces with a composite resin. The results showed that the overall morphologic etching effect was similar in both groups. The mean shear bond strength for group 1 was 11.8 MPa +/- 4.2, and for group 2 it was 16.5 MPa +/- 5.1. This difference was statistically significant (p less than 0.01). PMID- 1867168 TI - Rapid maxillary expansion in the primary and mixed dentitions: a cephalometric evaluation. AB - The present study evaluated the skeletal alterations induced by rapid maxillary expansion procedures in 30 patients in the primary and mixed dentitions. The results were obtained with the use of lateral cephalometrics before and immediately after the active phase of expansion. The time span between these two cephalometric films ranged from 14 to 21 days; therefore the "growth factor" was not considered. Based on the differences in the cephalometric measurements studied on the first and second tracings, it seems that anterior displacement of the maxilla with significant changes in the SNA angle should not be expected, although point B was repositioned more posteriorly (SNB) because of the mandibular downward and backward rotation, with subsequent increase of the inclination of the mandibular plane. The alterations in the A-P position of the mandible was reflected in the increase of ANB and NAP angles. The maxilla always dislocates downward, displaying a downward and backward rotation in the palatine plane, significantly altering the following measurements: N-ANS, PNS-PNS', A-A', SN.PP. The anchoring molars also follow the downward maxillary displacement (M M') and, as a direct consequence of the vertical displacement of the maxilla and upper molars (N-ANS, A-A', ANS-Me, N-Me, PNS-PNS'), the facial heights increase. PMID- 1867169 TI - Adolescent suicide in orthodontics: results of a survey. AB - Suicide among adolescents is a psychosocial problem that confronts today's teenagers and society in alarming proportions. The wounds from this tragedy scar adolescents and their families both physically and emotionally. By virtue of a tradition for early treatment and the periodic nature of orthodontic care during critical psychologic development, the orthodontist is in a position to recognize early warning signs of adolescent suicide. A survey of 1000 practicing orthodontists and 54 department chairpersons of orthodontic postgraduate programs assessed the relevance of this issue to the profession, the nature of educational information previously and currently available in orthodontic curricula, and the frequency with which suicidal behavior is noted in orthodontic practice. Guidelines for recognition and intervention are provided. The results indicate that (1) adolescent suicide is of concern to orthodontists, (2) academic information has focused on the general aspects of psychology but not on the recognition and intervention, and (3) 50% of those surveyed have had at least one patient attempt suicide, whereas 25% have had a young patient actually commit suicide. PMID- 1867170 TI - American Board of Orthodontics case report. AB - A case of a Class I malocclusion with a bimaxillary protrusion and an anterior crossbite is presented. [This case was presented to the American Board of Orthodontics in partial fulfillment of the requirements for the certification process conducted by the Board.] PMID- 1867171 TI - The Third International Workshop on Antineutrophil Cytoplasmic Autoantibodies. Introduction. PMID- 1867172 TI - How are antineutrophil cytoplasmic autoantibodies detected? AB - Antineutrophil cytoplasmic autoantibodies (ANCA) are present in patients with systemic vasculitis with or without renal involvement. These antibodies were first seen using indirect immunofluorescence (IIF). Two types of patterns are seen on ethanol-fixed neutrophils: the cytoplasmic and the perinuclear pattern. The cytoplasmic pattern is called C-ANCA (classical or cytoplasmic ANCA) and the perinuclear, P-ANCA. Antibodies to a serine proteinase, called proteinase 3 or myeloblastin, give rise to the C-ANCA pattern, while antibodies to myeloperoxidase give rise to the P-ANCA pattern. Proteinase 3, as well as myeloperoxidase, is present in the primary granules of neutrophils, and the P ANCA pattern is thus an artifactual staining pattern. Myeloperoxidase, which is a basic protein, redistributes during ethanol fixation from the primary granules to the negatively charged nucleus. As an alternative to the IF technique, several solid-phase assays have been developed using either 125I or enzyme-labeled secondary antibodies. Depending on the degree of purification of the antigens used, such assays may be used for screening or as a complement to the IF method. Today it is possible to directly screen for both types of ANCA using enzyme linked immunosorbent assay (ELISA). Simultaneous screening for antiglomerular basement membrane (GBM) antibodies (Goodpasture antibodies) increases the diagnostic yield, especially in patients with renopulmonary syndromes. PMID- 1867173 TI - Antineutrophil cytoplasmic autoantibody-associated diseases: a pathologist's perspective. AB - Antineutrophil cytoplasmic autoantibodies (ANCA) are a useful diagnostic serologic marker for the most common forms of necrotizing vasculitis, provide a means of categorizing vasculitides so that diagnostically useful shared pathologic and clinical characteristics can be recognized, and offer insight into the pathogenesis of previously idiopathic diseases. ANCA-associated vasculitides can be categorized into a number of distinctive clinicopathologic categories, eg, Wegener's granulomatosis, Churg-Strauss syndrome, pulmonary renal syndrome, microscopic polyarteritis nodosa, leukocytoclastic angiitis, and necrotizing and crescentic glomerulonephritis. At least the latter four syndromes can also be caused by other ANCA-negative immunopathogenic mechanisms, eg, immune complex deposition. Therefore, thorough diagnostic classification requires both an assessment of clinicopathologic category, as well as an assessment of immunopathologic category. Although different ANCA-associated vasculitic syndromes have distinctive clinical and pathologic features, all ANCA-associated vasculitides share a number of common pathologic features, ie, focal distribution, necrosis, and neutrophil infiltration. ANCA assays have very good sensitivity and specificity for ANCA-associated diseases, but the prevalence of these diseases in the patient population being analyzed must be taken into consideration when determining the predictive value of a test result. As with all serologic tests, ANCA results must be integrated with other clinical and pathologic data in order to reach the most accurate diagnostic conclusion. PMID- 1867174 TI - Antineutrophil cytoplasmic autoantibodies: the nephrologist's perspective. AB - Serologic tests for antineutrophil cytoplasmic autoantibodies (ANCA) provide diagnostic and prognostic information in patients with nephritis and systemic vasculitis. Four case histories are discussed that illustrate ANCA positivity in patients with renal impairment caused by interstitial, rather than glomerular, nephritis. Renal biopsy should continue to be used to diagnose the cause of renal impairment in ANCA-positive patients. PMID- 1867175 TI - Antineutrophil cytoplasmic autoantibody-associated diseases: a rheumatologist's perspective. AB - Autoantibodies against neutrophil cytoplasmic antigens (ANCA) produce two major immunofluorescence (IF) patterns on ethanol-fixed granulocytes: the "classical" (centrally accentuated) C-ANCA, associated with Wegener's granulomatosis (WG), and P-ANCA (perinuclear), which mainly occur in renal vasculitis. Rheumatic manifestations are an important clinical finding in systemic vasculitis, often preceding a fulminant course and sometimes imitating various rheumatic disorders. We analyzed the incidence of ANCA in rheumatic patients and looked for the frequency of rheumatic symptoms in systemic vasculitis. In WG (n = 186), we found rheumatic symptoms in 55% (myalgia, 45%; arthritis, 21%); in 90%, rheumatic complaints were associated with active vasculitis. In 730 patients with various rheumatic conditions (eg, 268 rheumatoid arthritis, 130 systemic lupus erythematosis [SLE], 32 sharp-S, 50 ankylosing spondylitis, 43 systemic sclerosis) no C-ANCA were found. On the contrary, the P-ANCA pattern was seen in seven of 62 giant cell arteritis, five of 27 Felty's/Still's syndrome, and four of 130 SLE patients in addition to renal vasculitis (21/74). We demonstrated that 95% of C-ANCA-positive sera react with proteinase 3 (PR3 or myeloblastin). Using monoclonal antibodies, we showed that PR3 is expressed on the plasma membrane of neutrophil granulocytes and monocytes; thus, PR3 autoantigens are accessible for circulating antibodies. The detection of ANCA in sera from vasculitis and other rheumatic diseases is of immunodiagnostic value and provides new insight in the pathogenesis of systemic vasculitides. PMID- 1867176 TI - Antineutrophil cytoplasmic autoantibody-associated diseases: a pulmonologist's perspective. AB - The development of the antineutrophil cytoplasmic autoantibody (ANCA) test has lent support to the concept of Wegener's granulomatosis as a spectrum that may affect one or more of the major anatomic sites: upper respiratory tract (E), lung (L), or kidney (K). It is C-ANCA that has high specificity for Wegener's granulomatosis (WG). The sensitivity is highest in the fully expressed Wegener's triad, or ELK, and less in local regional disease. It is possible that isolated manifestations such as episcleritis, subglottic stricture, or diffuse alveolar hemorrhage associated with C-ANCA may be considered in the Wegener's spectrum, although traditional histopathologic criteria are lacking. Until specific etiologic agents are uncovered for the various ANCA-associated entities, classification schemes should continue to employ previously established clinicopathologic syndromes such as WG using the ANCA test to better define their clinical spectrums. PMID- 1867177 TI - Diagnostic classification of antineutrophil cytoplasmic autoantibody-associated vasculitides. AB - Antineutrophil cytoplasmic autoantibodies (ANCA) are in the circulation of patients with a variety of clinically and pathologically distinctive forms of necrotizing vasculitis. Some patients have classic manifestations of well recognized clinicopathologic syndromes, such as Wegener's granulomatosis, microscopic polyarteritis nodosa, and Churg-Strauss syndrome, but many patients are difficult to assign to a diagnostic category. The Ad Hoc Nomenclature Committee of The Third International Workshop on ANCA is attempting to identify a working classification system for ANCA-associated vasculitides. This system takes into account the many shared clinical and pathologic features, and relies on prerequisite positive and negative findings for diagnostic categorization. PMID- 1867178 TI - Calcium and phosphorus fluxes during hemodialysis with low calcium dialysate. AB - We evaluated the acute effects of varying dialysate calcium concentration on plasma concentrations and dialyzer fluxes of calcium and phosphorus in adult hemodialysis patients. Seven individuals with stable end-stage renal failure were dialyzed 4 hours, three times weekly. The effects of dialysates containing 1.75, 1.25, or 0.75 mmol/L (70.1, 50.1, or 30.1 mg/L) of calcium were compared. Each patient was studied once at each bath calcium concentration. Compared with the predialysis mean value of 2.27 mmol/L (9.1 mg/dL), plasma total calcium concentration increased, remained constant, or decreased with the 1.75-, 1.25-, or 0.75-mmol/L calcium dialysates, respectively. The 0.75-mmol/L calcium dialysate did not cause signs or symptoms of hypocalcemia (and the plasma calcium concentration did not fall below 1.80 mmol/L [7.2 mg/dL]). Plasma phosphorus concentrations decreased equally from a predialysis mean value of 2.16 mmol/L (6.7 mg/dL), regardless of the dialysate calcium concentration. After 4 hours of treatment with the three different dialysates, the cumulative calcium fluxes were significantly different. With 1.75 mmol/L calcium, mean bodily calcium accumulation was 21.9 mmol (879 mg). With 1.25 mmol/L, there was no net calcium flux. With 0.75 mmol/L, mean patient calcium loss was 5.8 mmol (231 mg). Mean phosphorus removal after 4 hours was 32.5 mmol (1,006 mg) and was unaffected by dialysate calcium concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867179 TI - Randomized controlled trial of prophylactic rifampin for peritoneal dialysis related infections. AB - Staphylococcal infections are a major cause of catheter infections and peritonitis in peritoneal dialysis patients. Since catheter-related infections are associated with nasal carriage of Staphylococcus aureus in this population, we studied the effect of intermittent rifampin, an antibiotic known to decrease S aureus nasal carriage, on catheter-related infections and peritonitis. We randomly assigned 64 patients to receive either rifampin 300 mg twice daily for 5 days every 3 months or no treatment. The rifampin-treated patients had a significant delay in time to first catheter-related infection (P less than 0.015) and significantly fewer catheter-related infections overall (P less than 0.001). The catheter-related infection rate in rifampin-treated patients was .26 per patient-year versus .93 per patient-year in untreated patients. Multivariate analysis defined baseline colonization of nares or catheter exit-site and prior renal transplant as risk factors for catheter-related infections. There was no significant difference in peritonitis rates between groups, although the trend was for a delayed time to first episodes and fewer episodes in rifampin-treated patients. Adverse effects necessitated withdrawal of rifampin in four patients. We conclude that intermittent rifampin administration is effective in decreasing catheter-related infections in a peritoneal dialysis population. PMID- 1867180 TI - Anti-DNA idiotypes deposited in renal glomeruli of patients with lupus nephritis. AB - Idiotypes (Id) of human anti-DNA antibodies, designated as O-81 Id, were specifically detected on the immune deposits of renal glomeruli in 46% of patients with lupus nephritis. Id-binding to anti-Id antibodies was blocked by free O-81 Id and to some extent by free DNA. DNase or acid buffer treatment failed to reveal new Id determinants on the deposits. O-81 Id and NE-1 Id activity were also detected on the renal eluate-derived IgG, but not IgM from the autopsy cases with lupus nephritis. The incidences of O-81 Id were not associated with histological features in the glomeruli, but the distribution patterns were similar to those of IgG deposits. Our study also showed that 65% to 70% of patients with IgG deposits either in the subendothelium or in the subepithelial area of the glomerular basement membrane (GBM) showed positive tests for O-81 Id. It was also noted that most patients with massive proteinuria had O-81 Id in their glomeruli. It is concluded that O-81 Id deposits are relatively specific for active lupus nephritis and that immunofluorescence studies using anti-Id antibodies may be clinically useful for specifying the renal lesions of systemic lupus erythematosus (SLE). PMID- 1867181 TI - Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). AB - The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the "Gruppo Italiano per lo Studio della Nefrite Lupica" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867182 TI - Effectiveness of renal fellowship training for subsequent clinical practice. AB - To assess whether nephrologists perceive disparities between the skills learned during fellowship training and those necessary for clinical subspecialty practice, we surveyed the perception of board-certified American nephrologists regarding the effectiveness of their clinical training. A questionnaire was sent to all Diplomates of the American Board of Internal Medicine in the subspecialty of Nephrology who successfully passed the qualifying examination in 1974, 1980, and 1986, regarding the effectiveness of academic instruction within the clinical fellowship program as regards traditional academic subject matter, patient management, performance of procedures, and interpretation of laboratory data. Questionnaires were returned by 42.1%. Although respondents were generally satisfied with training in academic nephrologic subject matter, dissatisfaction with training in pediatric nephrology, transplant immunology, nephrolithiasis, nutrition, and renal function and disease in pregnancy was evident. Training was thought to be ineffective in theoretical and practical aspects of management of end-stage renal disease. In addition, respondents were dissatisfied with the effectiveness of their training in interpretation of radiologic tests and procedures such as gaining access to the circulation. More recently trained nephrologists were dissatisfied with training in outpatient management and interpretation of radiographic tests. Differences between perceptions of older and younger nephrologists were most marked regarding their preparation for gaining access to the circulation, interpretation of intravenous pyelography, and training for continuous ambulatory peritoneal dialysis (CAPD). To prepare fellows in training for the exigencies of clinical practice. Nephrology training programs will have to emphasize the teaching of the cognitive and manual bases of performing procedures, and provide more outpatient experience for trainees.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867183 TI - Pulmonary hemorrhage and necrotizing glomerulonephritis without glomerular immune deposits: report of two cases. AB - Two children with a syndrome of pulmonary hemorrhage and necrotizing, nonimmune glomerulonephritis are reported. A boy and girl, both of East Indian descent, developed recurrent lung infiltrates from the age of 3 months and 2 years, respectively. Both subsequently presented with pulmonary hemorrhage, fever, arthritis, hematuria, and nephrotic range proteinuria at 1.5 and 6 years of age, respectively. Renal biopsy in each case showed acute, severe, focal and segmental, necrotizing and crescentic glomerulonephritis without immune deposits. Subsequent renal biopsies revealed severe glomerular and tubulointerstitial scarring. No vasculitis or granulomas were seen on renal, skin, or lung biopsies. Antineutrophil cytoplasmic antibodies (ANCA) were not detected in sera taken 1.5 years in the boy and 3.5 years in the girl after the onset of renal disease. The boy was treated with prednisone, azathioprine, and plasmapheresis, but developed progressive renal impairment and commenced dialysis within 4 years. Subsequent to renal transplantation, he developed an immunoblastic lymphoma and died. The girl was treated initially with prednisone and later with cyclophosphamide. After 4 years, she had a normal glomerular filtration rate (GFR). While necrotizing nonimmune glomerulonephritis associated with pulmonary hemorrhage is rare, and cases are characteristically difficult to classify because of many overlapping features, it is possible that these children had a unique illness. PMID- 1867184 TI - Should intravenous immunoglobulin G be first-line treatment for acute thrombotic thrombocytopenic purpura? Case report and review of the literature. AB - Acute thrombotic thrombocytopenic purpura (TTP) is a rare and serious disease. Treatment with prednisone, anticoagulation, antiplatelet drugs, splenectomy, exchange transfusions, vincristine, and plasmapheresis may be effective in some patients, but the response to these therapies is inconsistent and all carry the potential for serious side effects. We, and others, have recently seen dramatic responses to intravenous (IV) immunoglobulin G (IgG) when other treatments have failed. Although IV IgG is expensive, its costs are low compared with those extended plasmapheresis regimens. Since the response to treatment can usually be evaluated within a few days and the side effects appear less than with other treatments, we believe a strong case can be made for the use of IV IgG as first line therapy for acute TTP. Continued multicenter studies are necessary to finally solve the problem of competing and confusing treatment attempts and synergism of treatment in acute TTP. PMID- 1867185 TI - Reversible changes in osmoregulation of vasopressin release due to impaired water excretion. AB - Studies of renal water handling and the effects of altered hydration and posture on the osmoregulation of vasopressin release were performed on a chronically hyponatremic patient with complete cervical spinal cord transection at the C-5 level. Acute oral water loading studies showed marked reduction in free water clearance and urine diluting ability, despite appropriate suppression of plasma vasopressin concentrations. Orthostatic reductions in arterial blood pressure during head-up tilting and following the assumption of sitting posture were also demonstrable, and may have contributed to, but could not fully account for, the defect in renal water excretion, which persisted in supine posture. Hypertonic sodium chloride infusion studies performed before fluid restriction showed that low preinfusion plasma osmolality was associated with a reduced osmotic threshold for vasopressin release, which was subsequently corrected by a period of fluid restriction that restored the patient's plasma osmolality to a normal level. This shift in osmotic threshold can be inferred from both linear regression and log linear regression analysis of the data. These studies show that marked impairment of renal water excretion coupled with unrestricted water intake can result in altered osmoregulation of vasopressin release in association with persistent plasma hypo-osmolality, which can be corrected by fluid restriction. PMID- 1867186 TI - Pheochromocytoma in a long-term hemodialysis patient. AB - A right adrenal tumor was found incidentally by renal echography in a 25-year-old man, who had been on hemodialysis for 4 years. Inquiry and clinical examination suggested pheochromocytoma, which was confirmed by plasma catecholamine measurements. Subsequent adrenalectomy was uneventful. Although hypertension, headache, and diaphoresis are common symptoms in a dialyzed patient, pheochromocytoma has to be eliminated in the presence of this clinical triad. PMID- 1867187 TI - Acute renal failure in a case of IgA nephropathy. PMID- 1867188 TI - Angiotensin-converting enzyme (ACE) inhibitors have been reported to induce or worsen anemia in patients on hemodialysis. PMID- 1867189 TI - XY chromosome nondisjunction in man is associated with diminished recombination in the pseudoautosomal region. AB - To assess the possible association between aberrant recombination and XY chromosome nondisjunction, we compared pseudoautosomal region recombination rates in male meiosis resulting in 47,XXY offspring with those resulting in 46,XY and 46,XX offspring. Forty-one paternally derived 47,XXYs and their parents were tested at six polymorphic loci spanning the pseudoautosomal region. We were able to detect crossing-over in only six of 39 cases informative for the telomeric DXYS14/DXYS20 locus. Subsequently, we used the data to generate a genetic linkage map of the pseudoautosomal region and found it to be significantly shorter than the normal male map of the region. From these analyses we conclude that most paternally derived 47,XXYs result from meiosis in which the X and Y chromosomes did not recombine. PMID- 1867190 TI - A multipoint linkage map of the distal short arm of the human X chromosome. AB - The distal portion of the short arm of the human X chromosome (Xp) exhibits many unique and interesting features. Distal Xp contains the pseudoautosomal region, a number of disease loci, and several cell-surface markers. Several genes in this area have also been observed to escape X-chromosomal inactivation. The characterization of new polymorphic loci in this region has permitted the construction of a refined multipoint linkage map extending 15 cM from the Xp telomere. This interval is known to contain the loci for the diseases X-linked ichthyosis, chondrodysplasia punctata, and Kallmann syndrome, as well as the cell surface markers Xg and 12E7. This region also contains the junction between the pseudoautosomal region and strictly X-linked sequences. The locus MIC2 has been demonstrated by linkage analysis to be indistinguishable from the pseudoautosomal junction. The steroid sulfatase locus has been mapped to an interval adjacent to the DXS278 locus and 6 cM from the pseudoautosomal junction. The polymorphic locus (STS) DXS278 was shown to be informative in all families studied, and linkage analysis reveals that the locus represents a low-copy repeat with at least one copy distal to the STS gene. The generation of a multipoint linkage map of distal Xp will be useful in the genetic dissection of many of the unique features of this region. PMID- 1867191 TI - Neuroanatomy in fragile X females: the posterior fossa. AB - The relative homogeneity of the neuropsychiatric phenotype in individuals with fragile (fra) X syndrome suggests that there are consistent central nervous system (CNS) abnormalities underlying the observed cognitive and behavioral abnormalities. In this study, the neuroanatomy of the posterior fossa and other selected CNS regions in 12 young fra X females were compared with those of a group of 12 age-, sex-, and IQ-matched females without evidence of the fra X syndrome. Fra X females were shown to have decreased size of the posterior cerebellar vermis and increased size of the fourth ventricle, findings that are identical to those previously reported for fra X males. When compared with fra X male and nonfra X control groups, the distribution of the posterior-vermis and fourth-ventricle variables for the fra X female group was intermediate. These results support the hypothesis that the fra X genetic abnormality leads to hypoplasia of the posterior cerebellar vermis, a neuroanatomical variation of potential importance to both developmental and neuropsychiatric syndromes. PMID- 1867192 TI - Direct detection of dystrophin gene rearrangements by analysis of dystrophin mRNA in peripheral blood lymphocytes. AB - Using 10 overlapping nested sets of primers and using peripheral blood lymphocyte (PBL) total RNA as template, we have developed a system, based on PCR, which allows the rapid production of double-stranded cDNA corresponding to the entire coding sequence of the dystrophin gene. The product can be visualized on native minigels by ethidium staining and directly sequenced after gel purification. We have used this system to analyze the structures of PBL dystrophin mRNA in 26 Duchenne, Becker, or intermediate muscular dystrophy patients who have gross rearrangements of the dystrophin gene. In each case, the effect that the genomic rearrangement has on the structure of the transcript--and, by inference, on the dystrophin protein--has been determined, and the results confirm the frameshift hypothesis. The study also identifies a series of alternatively spliced transcripts which are specific to the rearranged genotypes and which seem therefore to arise following the alteration in the context of the splice signal. The system has been used for unambiguous identification of carrier females. Furthermore, the rapid production of microgram quantities of dystrophin cDNA from a readily accessible tissue makes point-mutation screening a practical proposition. PMID- 1867193 TI - Nonradioactive assay for new microsatellite polymorphisms at the 5' end of the dystrophin gene, and estimation of intragenic recombination. AB - Indirect tracking of mutation by DNA polymorphisms is still essential for carrier and prenatal diagnosis of Duchenne/Becker muscular dystrophy, at least in the families where no deletion can be detected. Because of the relatively high level of intragenic recombination, informative and easily testable markers at both ends of the gene are necessary for efficient and accurate diagnosis. We report the characterization of two polymorphic microsatellite sequences (TG repeats) at the 5' end of the dystrophin gene, within 40 kb of the muscle-specific promoter. The most useful one (5' DYS MSA) has 10 alleles with a 57% heterozygosity and can be tested on small polyacrylamide gels in a nonradioactive PCR-based assay. Despite its large number of alleles, this microsatellite shows strong linkage disequilibrium with a two-allele polymorphism reported by Roberts et al., an indication of the stability of this type of sequences. We have used the new microsatellites at the 5' end, along with one we reported previously for the 3' end, to type the families in the CEPH (Centre d'Etude du Polymorphisme Humain) panel. While the number of informative families has increased by a factor of about two with respect to the study of Abbs et al., the estimates of the recombination fractions are in good agreement with this previous report, suggesting a 11% recombination across the gene (3% between the 5' end and the pERT87 region, 8% between pERT87 and the 3' end), which is about fivefold more than expected. However, these estimates still have wide confidence limits. PMID- 1867194 TI - The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations. AB - Application of uniform methods for measuring the apolipoprotein (apo) E polymorphism and plasma cholesterol levels in nine populations (Tyrolean, Sudanese, Indian, Chinese, Japanese, Hungarian, Icelandic, Finnish, and Malay) revealed significant heterogeneity among them in apo E type frequencies and mean cholesterol levels. The major apo E types in all populations were E3/2 (frequency range from 7.0% in Indians to 16.9% in Malays), E3/3 (frequency range from 39.8% in Sudanese to 72.1% in Japanese), and E3/4 (frequency range from 11.3% in Japanese to 35.9% in Sudanese). Mean cholesterol levels ranged from 144.2 mg/dl in the Sudanese to 228.5 mg/dl in the Icelandics. Two-way analysis of variance of the effect of population and apo E type on cholesterol levels showed no significantly interaction effect, indicating that the effects of apo E type on cholesterol levels do not differ significantly among the populations. The overall average excess for the epsilon 2 allele was -14.12 mg/dl (range -31.63 to -8.82 mg/dl); for the epsilon 3 allele, 0.04 mg/dl (range -1.87 to 1.58 mg/dl; and for the epsilon 4 allele, 8.14 mg/dl (range -1.71 to 13.31 mg/dl). Despite the apparent heterogeneity in these values, especially for the epsilon 4 allele, comparison of the average excesses by a method of repeated sampling with random permutations revealed no significant difference in effects among populations. These data indicate that a given apo E allele acts in a relatively uniform manner in different populations despite differences in genetic background and environmental factors. PMID- 1867195 TI - Torsion dystonia genes in two populations confined to a small region on chromosome 9q32-34. AB - Idiopathic torsion dystonia (ITD) is characterized by sustained, involuntary muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Most familial forms of ITD display autosomal dominant inheritance with reduced penetrance. Linkage analysis has been previously used to localize a dystonia gene to the 9q32-34 region in a large non-Jewish family and in a group of Ashkenazi Jewish families. Utilizing GT repeat polymorphisms from this region, here we demonstrate that the gene causing dystonia in Ashkenazi Jews can be localized to the 11-cM interval between AK1 and D9S10. Linkage analysis in the non-Jewish family is also consistent with occurrence of the gene in this region, although positive lod scores extend over a greater than 20-cM interval in that family. These results set the stage for positional cloning of the dystonia gene. Currently there are no known candidate genes in this region. PMID- 1867196 TI - A genetic study of platelet adenylate cyclase activity: evidence for a single major locus effect in fluoride-stimulated activity. AB - The activity of membrane-bound platelet adenylate cyclase, when stimulated in vitro by several compounds (including fluoride), is significantly reduced in alcoholics compared with control subjects. We have begun a study of the genetics of this enzyme activity. Complex segregation analysis of basal (unstimulated) platelet adenylate cyclase activity in families reveals a mode of inheritance that cannot be accounted for by a simple mixed model of transmission. By contrast, adenylate cyclase activity stimulated by fluoride ion reveals a single major locus effect with a modest multifactorial background. These results suggest that a single factor in the second-messenger pathway may (a) account for the majority of individual differences in stimulation of adenylate cyclase of fluoride and (b) help explain the reduced activities previously observed in alcoholics. PMID- 1867197 TI - Compound heterozygosity in nonphenylketonuria hyperphenylalanemia: the contribution of mutations for classical phenylketonuria. AB - Hyperphenylalaninemia (HPA) results from defective hydroxylation of phenylalanine in the liver, in most cases because of defective phenylalanine hydroxylase. HPA is highly variable, ranging from moderate elevation of plasma phenylalanine with no clinical consequences to a severe disease, classical phenylketonuria (PKU). Non-PKU HPA was found in excess of PKU in Israel, while the opposite is true in Europe. To study the genetic basis of non-PKU HPA, we performed haplotype analysis at the phenylalanine hydroxylase locus in 27 families with non-PKU HPA. All individuals with this condition were compound heterozygotes. In six of these families, in which both PKU and non-PKU HPA were segregating, haplotype analysis showed that non-PKU HPA resulted from compound heterozygosity for a PKU mutation and a second mutation, with milder effect, which is probably expressed only when it interacts with the severe mutation. The involvement of PKU mutations in non PKU HPA was further demonstrated in Jewish Yemenite families with non-PKU HPA, in which the individuals with this condition were carriers of the single PKU allele which exists in this community. In addition, two previously known PKU point mutations (R261Q and R408W) were found in individuals with non-PKU HPA. These mutations are associated, in our population, with the same haplotypes as those with which it is associated in Europe. Based on the above-mentioned genetic model for non-PKU HPA, successful prenatal diagnosis of this condition was performed in one family.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867198 TI - Characterization of a COL1A1 splicing defect in a case of Ehlers-Danlos syndrome type VII: further evidence of molecular homogeneity. AB - A child affected by the type VII form of Ehlers-Danlos syndrome (EDS VII) was shown to have a heterozygous structural defect in the amino-terminus of pro-alpha 1(I) collagen. As a result, type I procollagen trimers containing defective subunits are not converted to mature collagen molecules. To identify the cause of the protein abnormality, specifically primed cDNAs and genomic DNA were PCR amplified and sequenced. This analysis disclosed that the protein structural defect is caused by a single base substitution (A for G) at position -1 of the splice donor site of intron 6 of the pro-alpha 1(I) collagen gene (COL1A1). The affected allele produces (a) transcripts lacking exon 6 sequences and (b), in lesser amount, normally spliced transcripts. Furthermore, the rate of exon 6 skipping is temperature dependent, for it appears to decrease substantially when the patient's fibroblasts are incubated at 31 degrees C. These findings are similar to those we previously reported for other unrelated EDS VII cases and, therefore, reemphasize the molecular homogeneity of this rare connective tissue disorder. PMID- 1867199 TI - Occurrence of a Tyr393----Asn (Y393N) mutation in the E1 alpha gene of the branched-chain alpha-keto acid dehydrogenase complex in maple syrup urine disease patients from a Mennonite population. AB - Maple syrup urine disease (MSUD) is caused by a deficiency in the mitochondrial branched-chain alpha-keto acid dehydrogenase complex. The incidence of MSUD in the Philadelphia Mennonites is 1/176 births resulting from consanguinity. In this study, we amplified cDNAs for the decarboxylase E1 alpha subunit of the branched chain alpha-keto acid dehydrogenase complex from a classical MSUD patient and from an obligatory heterozygote of a Mennonite family by the PCR. Sequencing of the amplified cDNAs disclosed at codon 393 of the mature E1 alpha polypeptide a base substitution changing a tyrosine (encoded by TAC) to an asparagine residue (encoded by AAC), which is designated Y393N. A segment of the E1 alpha gene containing the 5' portion of exon 9 was amplified. Probing of the amplified genomic DNA with allele-specific oligonucleotide probes showed that the mutation in the E1 alpha gene was homozygous in six Mennonites affected with classical MSUD and was present in heterozygous carriers. The identification of the MSUD mutation in the Philadelphia Mennonites will facilitate diagnosis and carrier detection for this population. PMID- 1867200 TI - A common Lithuanian mutation causing familial hypercholesterolemia in Ashkenazi Jews. AB - Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low-density-lipoprotein (LDL) receptor. Here we characterize an LDL-receptor founder mutation that is associated with a distinct LDL-receptor haplotype and is responsible for FH in 35% of 71 Jewish-Ashkenazi FH families in Israel. Sixty four percent (16/25) of the Ashkenazi patients who carry this mutant allele were of Lithuanian origin. The mutation was not found in 47 non Ashkenazi FH families. This mutation was prevalent (8/10 FH cases) in the Jewish community in South Africa, which originated mainly from Lithuania. The mutation, a 3-bp in-frame deletion that would result in the elimination of Gly197, has been previously designated FH-Piscataway. PCR amplification of a DNA fragment that includes the mutation in heterozygous individuals results in the formation of a heteroduplex that can be demonstrated by PAGE and used for molecular diagnosis. PMID- 1867202 TI - Chromosome 15 uniparental disomy is not frequent in Angelman syndrome. PMID- 1867203 TI - The use of a new multiplex PCR assay significantly improves the rapid detection of deletions in the dystrophin gene. PMID- 1867201 TI - Are the Basques a single and a unique population? AB - Different analyses of genetic polymorphisms performed on the Basque population have suggested a possible heterogeneity of the Basques and a singularity of their genetic characteristics. In this paper, both aspects are analyzed by means of the genetic study of seven polymorphic systems--ACP, ADA, AK, ESD, PGD, GC, and HP- in 854 autochthonous individuals from the province of Vizcaya. The individuals were classified as being from the regions of Arratia, Guernica, Durango, Uribe, Marquina, Lea, and Bilbao, on the basis of the birthplaces of their four grandparents. Analyses for heterogeneity of the gene frequencies distribution suggest that there is a moderate genetic heterogeneity, probably produced by centuries of geographical and administrative isolation of these regions. The comparison with caucasoid populations, performed using the principal components analysis and Cavalli-Sforza and Edwards arc distance, indicates that the subpopulations of the province of Vizcaya have experienced little genetic exchange with other caucasoids and that the distribution of their genetic frequencies differentiates them from other populations. PMID- 1867204 TI - Estimation of an approximate confidence interval for FRAXA location by using linkage data from many pedigrees. PMID- 1867206 TI - Prenatal screening for hemoglobinopathies. PMID- 1867205 TI - Diabetic pregnancy: is there intrauterine selection of ADA polymorphism? PMID- 1867207 TI - Historical perspectives. PMID- 1867208 TI - Defining the gene: an evolving concept. PMID- 1867209 TI - ASHG/NSGC activities related to education. The doctoral degree in genetic counseling: attitudes of genetic counselors. AB - All 565 full members of the National Society of Genetic Counselors were surveyed in September 1989 to assess their attitudes toward a potential doctoral degree in genetic counseling. The usable return rate was 59.6% (337/565) of the full membership. One hundred eighty (54.4%) respondents indicated a need for a doctoral degree in genetic counseling, 101 (30.5%) were undecided as to the need, and 50 (15.1%) did not see a need for such a degree. One hundred forty-seven (44.3%) respondents indicated their individual interest in pursuing a doctorate in genetic counseling, 109 (32.8%) would not pursue such a degree, and 76 (22.9%) were undecided. Beyond the generally accepted feeling that genetic counseling should expand as a professional field, the reasons cited most often for seeking the Ph.D. in genetic counseling were professional recognition, a desire to specialize in a particular area, and greater depth of knowledge. The study revealed a strongly positive attitude, among full members of the NSGC, toward establishment of a doctoral degree in genetic counseling. PMID- 1867210 TI - Innovations in human genetics education. Medical student elective in clinical genetics. AB - The fourth-year medical student elective in clinical genetics has been enhanced by the addition of a problem-solving project. The assignment requires students to pose and answer a practical question about a professionally relevant genetic problem. Exemplary questions and the details of the exercise are given. Six of 10 students choosing an elective in clinical genetics have undertaken the project. Their feedback suggests that the requirements of decision making, library research, discussion with consultants, and medical writing in a limited time period are beneficial additions to the standard elective. PMID- 1867211 TI - Teaching about the human genome project. PMID- 1867212 TI - Radiographic abnormalities in asbestos insulators: effects of duration from onset of exposure and smoking. Relationships of dyspnea with parenchymal and pleural fibrosis. AB - Chest radiographs and spirometry were evaluated in 2,907 active and retired asbestos insulators; most (86.8%) had greater than or equal to 30 years from onset of asbestos exposure. Testing was performed in 19 cities in the United States during 1981-1983. Complete demographic, smoking, clinical, and radiologic data were obtained for 2,790 workers. This is the largest single group of insulators that has been studied. Five hundred forty-eight (19.7%) had never smoked cigarettes, 942 (33.9%) were current cigarette smokers, and 1,300 (46.6%) were ex-smokers. Only 439 (15.7%) workers had no radiographic evidence of asbestos-related disease (normal chest X-ray); 668 (23.9%) had pleural fibrosis only, 325 (11.6%) had parenchymal fibrosis alone, and 1,358 (48.7%) had both parenchymal and pleural fibrosis. The prevalence of radiographic parenchymal changes increased significantly (p less than .001) from 38.6% (DURONSET less than 30 years) to 70% (greater than or equal to 40 years). For pleural changes the comparative prevalences were 55% and 82%. Those with no history of cigarette smoking were more likely to have normal films than those with a history of smoking (19.2% versus 14.4% for current smokers and 15.2% among ex-smokers), and were less likely to have parenchymal fibrosis (44.5% versus 69.7% for current smokers and 60.2% of ex-smokers). Dyspnea, MRC grade 3 and higher, was more prevalent when pleural fibrosis was associated with interstitial pulmonary fibrosis (at all profusion levels of small opacities) than when pleural fibrosis was absent. Logistic regression analysis of factors contributing to such dyspnea showed that the presence of combined parenchymal and pleural abnormalities was a significant explanatory variable, in addition to age, smoking, and body mass (Quetelet index); the presence of parenchymal changes only or of pleural changes only, as factors contributing to dyspnea, did not reach the level of statistical significance in the regression analysis. The results of these examinations show that pleural fibrosis is a frequent finding in asbestos-exposed groups with long term follow-up and that its functional significance is not negligible. The contribution of cigarette smoking to prevalence and severity of interstitial fibrosis is an additional reason for smoking cessation among asbestos-exposed individuals. PMID- 1867213 TI - Biological monitoring of the occupational exposure to halothane (fluothane) in operating room personnel. AB - The concentration of halothane (fluothane) in the ambient atmosphere was determined in five operating theaters of two hospitals in Italy. The concentrations of halothane in the ambient air exceeded the NIOSH recommended time-weighted average exposure levels (median value: 10.38 mg/m3). Halothane was detected in the urine of 58 exposed subjects (anesthetists, surgeons, and nurses). A significant correlation was found between the halothane concentration in urine produced during the shift (Cu, micrograms/L) and halothane environmental concentration (CI, mg/m3) (Cu = 0.242 x CI + 3.51) (N = 58; r = 0.92; p less than 0.0001). The results show that the urinary halothane concentration can be used as an appropriate biological exposure index. The biological values proposed are: 92 micrograms/L, corresponding to a 50 ppm of environmental exposure; 6.5 micrograms/L, corresponding to 2 ppm of environmental exposure and 3.9 micrograms/L, corresponding to a 0.5 ppm of environmental exposure. PMID- 1867214 TI - Renal cell carcinoma among architects. AB - Data from a population-based cancer registry were analyzed according to occupation and industry at the time of diagnosis as part of a routine surveillance of the data for associations between occupation and cancer risk. A total of 119 cases of cancer of all sites were reported among architects between 1972-1986. From a total of 2,059 renal cell carcinomas in the registry, the 13 cases were observed among male architects, aged up to 64, 3.1 were expected. Significant elevations were not observed among other professional groups. Architects are exposed to several toxic and potentially carcinogenic chemicals. We suggest that investigators with cancer registry data coded according to occupation evaluate whether an association between employment as an architect and renal carcinoma exists in their data. PMID- 1867215 TI - Parental occupational exposures and risk of childhood cancer: a review. AB - We reviewed the literature in order to summarize the present knowledge on the association between parental occupational exposures to chemicals and the risk of childhood malignancy. The 32 studies pertaining to this topic were evaluated by considering various study qualities such as sample size, specificity of outcome, confounding, exposure specificity, and control selection. When evaluating the findings from any epidemiologic study, the potential sources of bias have to be considered. The selection of subjects, misclassification of exposure or outcome, and confounding from extraneous factors can contribute to a biased estimate of effect. Studies done to minimize these potential biases will be more valid, and these studies should be given the most weight when parental occupational exposures are evaluated as risk factors for childhood malignancy. We conclude that the preponderance of evidence supports the hypothesis that occupational exposure of parents to chemicals increases the risk of childhood malignancy. The parental occupational exposures implicated in childhood malignancy risk are exposure to chemicals including paints, petroleum products, solvents (especially chlorinated hydrocarbons) and pesticides, and exposure to metals. The available data do not allow the identification of specific etiologic agents within these categories of compounds. Future epidemiologic and toxicologic studies should be designed to pursue these leads. PMID- 1867216 TI - Silicon carbide pneumoconiosis: a radiographic assessment. AB - Interstitial lung disease and airflow limitation have been reported in silicon carbide workers but it is uncertain whether these recent observations reflect past working conditions alone (30 years ago) or both past and present conditions even if the latter have improved. To investigate this, we analyzed pairs of chest radiographs obtained in 1977 and 1984 in 128 silicon carbide plant workers. Three indices, related to density of small opacities, profusion of opacities, and presence of pleural plaques, were obtained. Student t-tests on results obtained in each time period showed the mean density (1.02 in 1977 and 0.56 in 1984) and profusion (4.27 in 1977 and 2.13 in 1984) indices to be significantly different. However, the pleural plaque index was not different in 1984 (0.34) as compared with 1977 (0.32). There was no deterioration of the radiographic image even in groups with density ratios equal or greater than 1/1. We concluded that the actual environmental working conditions did not influence the integrity of the lung radiographic image in these workers within a time span of 6 or 7 years. PMID- 1867217 TI - Inflammation of the visceral pleura, a nonspecific asbestos-related pleural reaction: chest radiograph and computed tomograph correlation. AB - Nonspecific pleuritis, i.e., inflammation of the visceral pleura, is recognized by the presence of pleural strands on the routine posteroanterior chest radiograph. The computed tomograph counterparts of these strands are seen as interlobular septal intrusions and lenticular or wedge-shaped subpleural opacities. The pleural reaction is nonspecific and may be found with asbestos exposure, traumatic hemorrhagic effusions, pulmonary embolism, viral pleurisy, malignant pleural effusions, and lupus or rheumatoid effusions. The asbestos related pleural changes may be found alone or in association with parietal pleural plaque formation or with asbestotic lung fibrosis. PMID- 1867218 TI - Silicosis and lung cancer in North Carolina dusty trades workers. AB - Since 1940, 760 cases of silicosis have been diagnosed as part of the State of North Carolina's (NC) pneumoconiosis surveillance program for dusty trades workers. Vital status was ascertained through 1983 for 714 cases that had been diagnosed since 1940 and death certificates were obtained for 546 of the 550 deceased. Mortality from tuberculosis, cancer of the intestine and lung, pneumonia, bronchitis, emphysema, asthma, pneumoconiosis, and kidney disease was significantly increased in whites. Mortality from tuberculosis, ischemic heart disease, and pneumoconiosis was significantly increased in non-whites. The standardized mortality ratio (95% CI) for lung cancer based on U.S. rates was 2.6 (1.8-3.6) in whites, 2.3 (1.5-3.4) in those who had no exposure to other known occupational carcinogens, and 2.4 (1.5-3.6) in those who had no other exposure and who had been diagnosed for silicosis while employed in the NC dusty trades. Age-adjusted lung cancer rates in silicotics who had no exposure to other known occupational carcinogens were 1.5 (.8-2.9) times higher than that in a referent group of coal miners with coalworkers' pneumoconiosis (CWP) and 2.4 (1.5-3.9) times higher than that in a referent group of non-silicotic metal miners. Age- and smoking-adjusted rates in silicotics were 3.9 (2.4-6.4) times higher than that in metal miners. This analysis effectively controls for confounding by age, cigarette smoking, and exposure to other known occupational carcinogens, and it is unlikely that other correlates of silica exposure could explain the excess lung cancer mortality in the silicotics. PMID- 1867219 TI - First-aid reports of acute chlorine gassing among pulpmill workers as predictors of lung health consequences. AB - Workers in pulpmills can be exposed to a multitude of gases hazardous to respiratory function, the most common of which is chlorine gas. First-aid reports of acute gas overexposure incidents ("gassings") over an 8 year period were used to generate exposure data on a group of pulpmill workers whose respiratory function had been studied cross-sectionally in 1981 and 1988. Three hundred forty eight incidents representing 174 workers were identified, 78% of these being treated solely by the first-aid attendant with the administration of O2 and cough suppression medication. Among 316 workers tested during a 1988 respiratory health survey, 78 had at least one chlorine or chlorine dioxide "gassing" incident. There was a significant decrease in the FEV1/FVC ratio (p less than .05) as well as increased risk for workplace associated chest symptoms in this group with at least one "gassing" incident. In an age- and smoking-matched analysis, among workers tested both in 1981 and 1988, there was a greater decline in FEV2/FVC ratio and MMF (p less than .05) in the "gassed" group than in the nonexposed group over the 7 year period of observation. These results emphasize the need for worker protection against accidental chlorine gas exposures. PMID- 1867221 TI - Brain damage caused by hydrogen sulfide: a follow-up study of six patients. AB - Hydrogen sulfide (H2S) poisoning involves a risk of hypoxic brain damage. Six patients who lost consciousness due to H2S poisoning are described. The symptoms varied from anosmia in the patient with the shortest but highest exposure to delayed neurological deterioration in the patient with the longest exposure. The two patients with the most serious symptoms developed pulmonary edema, which may have prolonged the hypoxia. The patients were reexaminated 5 years or more after the poisoning. The five patients who had been unconscious in H2S atmosphere for from 5 to 15-20 min showed persisting impairment at neurological and neuropsychological re-examination. Memory and motor function were most affected. One patient was seriously demented. Recent reports of large groups of H2S poisoned workers probably underestimate the risk of sequelae, due to the inclusion of cases with exposure of short duration and lack of follow-up. PMID- 1867220 TI - Mortality study of British pathologists. AB - Pathologists eligible for inclusion in the study were identified from the membership lists of the Royal College of Pathologists from 1974 to 1987, establishing a population of 4,512 members. Overall mortality was lower among the study group compared with the general population of England and Wales, although there were significantly more deaths due to suicide (observed 13, expected 4.9, SMR 265, 95% CI 141-454). Excess deaths due to cancer of the lymphatic and hemopoietic system were noted but they were not significantly increased. An excess of brain cancer death was marginally significant for male pathologists (observed 6, expected 2.5, SMR 240, 95% CI 88-522). Six of the 9 (66.7%) cases of all types of brain tumors reported in total were among hematologists, although this sub-specialty comprises approximately 16% of all pathologists. PMID- 1867222 TI - Hypertension: meeting therapeutic challenges, providing effective management. PMID- 1867223 TI - Hypertension: meeting therapeutic challenges, providing effective management. Proceedings of a symposium. October 19-21, 1990, Laguna Niguel, California. PMID- 1867224 TI - Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia. AB - Epidemiologic studies have shown that insulin is a risk factor for coronary heart disease (CHD). Clinical studies have also demonstrated positive correlations between insulin and blood pressure, triglycerides, total cholesterol, fibrinogen, and plasminogen activator inhibitor. Moreover, there is an inverse correlation between insulin and high-density lipoprotein (HDL). These studies have provided evidence in support of the biologic plausibility of epidemiologic observations, but they have not clearly established insulin's role in the pathogenesis of human cardiovascular diseases (CVD) such as hypertension. In fact, there is considerable evidence that insulin resistance (abnormal nonoxidative glucose disposal), not hyperinsulinemia, is the primary insulin-related abnormality in human hypertension, and that hyperinsulinemia occurs as a response to insulin resistance. Skeletal muscle appears to be the primary site of insulin resistance in essential hypertension, although other organs, such as the kidneys and liver- key sites for cell and water homeostasis and lipoprotein regulation, respectively -may respond normally to insulin. Adipocytes also appear to be a site of insulin resistance. Thus, the putative interrelationship between hyperinsulinemia and insulin resistance, on the one hand, and with blood pressure and lipoproteins, on the other, is a complex one and may involve organ-specific insulin resistance. Altered cation transport is one of several mechanisms by which insulin resistance might raise blood pressure. The Na+, K(+)-ATPase and Ca(2+)-ATPase pumps are insulin sensitive. Thus, when insulin resistance is present, the activity of these pumps in the smooth muscle of the arterial wall might be reduced. This would lead to an intracellular accumulation of sodium and calcium, thereby sensitizing the vascular wall to pressor substances. Moreover, secondary hyperinsulinemia will occur, and insulin has been shown to stimulate sympathetic nervous system activity and to increase renal tubular absorption of sodium. Insulin is also a growth factor and therefore might have a trophic effect on the vessel wall, one that could initiate and/or sustain hypertension as well as atherosclerosis. Abnormal lipoprotein metabolism is yet another possible explanation for the accelerated atherosclerosis that has been observed in persons with abnormal carbohydrate tolerance and insulin resistance. Hyperinsulinemia and insulin resistance both play a role in the expression of elevated very-low density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels as well as in the depression of HDL levels. Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers. Thiazides and some beta blockers may further impair tissue insulin sensitivity and often cause blood lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1867225 TI - Therapeutic adherence in the elderly: transdermal clonidine compared to oral verapamil for hypertension. AB - This double-blind, double-dummy, randomized clinical trial, conducted in elderly patients with mild hypertension, compared adherence to treatment, efficacy, side effects, and quality of life during treatment with transdermal clonidine versus oral sustained-release verapamil (verapamil-SR). Blood pressure declined significantly--from 148/95 mm Hg at baseline to 139/84 after titration and 135/86 after maintenance--with transdermal clonidine (n = 29), and from 156/96 to 144/85 and 148/88, respectively, with verapamil-SR (n = 29). Adverse event rates and quality-of-life questionnaire responses were similar in the two treatment groups. Transdermal clonidine was worn as directed during more than 96% of patient-weeks of treatment. Compliance with the oral verapamil regimen was less consistent: Verapamil-SR was taken as directed during approximately 50% of patient-weeks of therapy, and individual compliance, assessed by tablet counts, varied from 50 120%. In all, 86% of subjects were satisfied or highly satisfied with the convenience of transdermal therapy; 87% reported that side effects were slightly or not bothersome; 65% indicated that transdermal patches were more convenient than oral therapy; and almost 60% preferred transdermal to oral therapy. In this study transdermal clonidine and oral verapamil were equally safe and effective. A substantial majority of patients preferred transdermal to oral therapy, and adherence to treatment was greater with transdermal therapy. PMID- 1867226 TI - Hypertension, cardiac disease, and compliance in minority patients. AB - In minorities, as in the general population, hypertension is taken seriously because it is a risk factor for cardiovascular disease. Until recently, our understanding of the role that hypertension plays in the heart disease seen in minorities has been limited by a paucity of prospective data regarding the prevalence, natural history, and pathophysiology of the disease process in minority populations. In the last few years large-scale epidemiologic studies and well-controlled clinical studies alike have confirmed usually high rates of hypertension-related morbidity and mortality in minorities, particularly blacks and Hispanics. The severity of end-organ damage, both cardiac and renal, that is seen in these patients--especially when coupled with the severe cerebrovascular damage that is also more common in black and Hispanic hypertensives--mandate that more effective public health measures be taken to reduce the incidence of hypertension in these patient populations. Because hypertension is usually without significant clinical symptoms, noncompliance with drug therapy and high dropout rates are common in all patient populations. They are strikingly higher in inner-city populations, however, where illiteracy, poverty, homelessness, and high rates of chemical dependency combine to exacerbate an already serious problem in treating hypertensive patients. Inner-city patients are, increasingly, black and Hispanic patients, and these patients are more likely to be underinsured or uninsured, to be functionally illiterate in English, to be disinclined to seek health care, and to be less capable of following a prescribed regimen than the populace as a whole. The nature of the therapeutic regimen itself is probably the most important determinant of compliance, and compliance with drug therapy will be improved if the clinic chooses a simplified drug regimen and avoids drugs that produce intolerable side effects. Once-a-day--or, with transdermal clonidine, one-a-week--single-drug therapy may not be possible in all patients, but multiple drug therapy and multiple daily dosing schedules should be avoided wherever possible. PMID- 1867227 TI - Improving compliance in an inner-city hypertensive patient population. AB - Because hypertension is a "silent" disease process, compliance with therapy is always a problem. In the inner city, where socioeconomic factors such as poverty, illiteracy, and substance abuse raise additional barriers to effective health care, poor compliance with antihypertensive regimens can reach epidemic proportions--as it did in our clinic in the early 1970s. After identifying the major causes of poor compliance in our patients, we instituted measures that led directly to greatly improved compliance and control, among them the expansion of clinic hours, the expediting of laboratory services, and the training of nurse therapists to assume many of the responsibilities of running the clinic. In recent years a number of new antihypertensive agents have been introduced, and these new drugs have afforded patients better blood pressure control through less complex drug regimens with fewer serious side effects. Indeed, we observed a strong correlation between patient compliance and the administration of agents with longer dosing intervals and improved side effects profiles. This observation led us to consider whether transdermal clonidine--which requires weekly, rather than daily, administration--might not be an especially effective means of controlling blood pressure in inner-city patients. To test this hypothesis, we enrolled 20 patients, all of them blacks, in a pilot study of this unique delivery system. Blood pressure was adequately controlled in all 18 patients who completed the study, and patients were uniformly enthusiastic about this alternative to daily dosing. As a result, compliance with this mode of therapy was excellent. PMID- 1867228 TI - Cardiovascular and metabolic characteristics of hypertension. AB - Hypertension is now seen as a broader condition than high blood pressure alone. Large-scale epidemiologic studies have established that high blood pressure is associated with an increased risk of cardiovascular events, but clinical trials of antihypertensive therapy have shown an inconsistent reduction in major cardiovascular endpoints. Importantly, the incidence of coronary disease has been reduced to only a small extent, suggesting that factors beyond high blood pressure are important in the genesis of atherosclerotic disease in hypertensive patients. It is evident, for example, that patients with hypertension have an exaggerated vulnerability to the consequences of lipid abnormalities. Moreover, it has recently been established that hypertension is characterized by insulin resistance and altered glucose tolerance. As a result, high plasma concentrations of insulin produce proliferative effects on vascular smooth muscle and connective tissue, and they may adversely affect the lipid profile. The left ventricle is also involved in hypertension--independent of blood pressure. There is growing evidence that there are increases in the muscle mass of the left ventricle and changes in its diastolic filling characteristics at the very early stages of hypertension. The arterial circulation is similarly involved, for alterations in structure or function, reflected by diminished arterial compliance, can be demonstrated prior to the appearance of clinical hypertension. Treatment designed to protect hypertensive patients from cardiovascular events must not only be based on blood pressure, but must take into account all the components of the hypertension syndrome. PMID- 1867229 TI - Hypercholesterolemia: new findings and clinical applications. Introduction. PMID- 1867230 TI - Hypercholesterolemia: new findings and clinical applications. Proceedings of a symposium. April 25, 1990, Chicago, Illinois. PMID- 1867231 TI - Regression of coronary atherosclerosis: an achievable goal? Review of results from recent clinical trials. AB - During the past decade, large, placebo-controlled, randomized trials have demonstrated that the incidence of coronary events can be reduced by treating hyperlipidemia. In studies with angiographic end points, marked lowering of total and low-density-lipoprotein cholesterol with comparable increases in high-density lipoprotein cholesterol retards the progression of coronary atherosclerosis and favors regression. In the Cholesterol-Lowering Atherosclerosis Study (CLAS), such therapy also prevented the appearance and worsening of atherosclerotic lesions in coronary bypass grafts. In the recently reported Familial Atherosclerosis Treatment Study (FATS), in which coronary lesions were measured quantitatively, treatment induced clear regression of coronary atherosclerosis and also markedly decreased coronary events. The beneficial effect on coronary lesions in these studies appears to be proportional to the degree of lipid lowering. In addition, new evidence suggests that aspirin and calcium antagonists might prevent the development of early coronary lesions. The identification and aggressive treatment of patients with high serum cholesterol levels can have a major impact on the development and evolution of coronary atherosclerosis. PMID- 1867232 TI - Expanded clinical evaluation of lovastatin (EXCEL) study results: III. Efficacy in modifying lipoproteins and implications for managing patients with moderate hypercholesterolemia. AB - In the multicenter, double-blind EXCEL (Expanded Clinical Evaluation of Lovastatin) study the efficacy of lovastatin in modifying plasma lipids and lipoproteins in 8,245 participants with moderate primary hypercholesterolemia was evaluated. Patients were randomly assigned to 48 weeks of treatment with diet and placebo or diet and lovastatin 20 or 40 mg once a day, or 20 or 40 mg twice a day. At all of these dosages, lovastatin produced substantial dose-dependent reductions in low-density-lipoprotein (LDL)-cholesterol levels, averaging 24% (20 mg/day) to 40% (80 mg/day). The magnitude of the effect of this lipoprotein was further reflected by the percentage of patients who achieved National Cholesterol Education Program (NCEP) goals. In the absence of coronary artery disease (CAD) or two other CAD risk factors, the LDL-cholesterol goal of 4.14 mmol/L (160 mg/dL) was attained by 22% of patients in the placebo group and between 81% (20 mg/day) and 96% (80 mg/day) of those treated with lovastatin. For those with CAD or at least two other CAD risk factors, the LDL-cholesterol goal of 3.36 mmol/L (130 mg/dL) was attained by 4% of placebo patients and between 38% (20 mg/day) and 83% (80 mg/day) of those treated with lovastatin. Lovastatin also increased high-density-lipoprotein cholesterol (7-10%) and decreased triglycerides (10-19%) in a dose-dependent manner. Thus, when used as an adjunct to a prudent diet, lovastatin produces favorable changes in the entire lipoprotein profile and is a highly effective agent for managing patients with primary hypercholesterolemia. PMID- 1867233 TI - Update on the pathogenesis of atherosclerosis. AB - The major components of atherosclerotic plaque, ultimately responsible for clinical effects, are deposited lipids--mostly cholesteryl esters and cholesterol, derived largely from the lower-density lipoproteins of the blood- and proliferated, modified arterial smooth muscle cells with their synthesized connective tissue products. Advanced plaques vary widely in the proportion of the two components, but evidence indicates that lipid deposition--especially of lipoprotein elements--often occurs in the lesion-prone intimal areas of the artery prior to the buildup of smooth muscle cells. The 1980s were remarkably productive for investigators who study the pathogenesis of atherosclerosis. We now know of the many forms of lower-density lipoproteins, i.e., low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), some of which are more likely to be associated with accelerated atherosclerosis and some of which are more likely to be influenced by diet. Among these forms of LDL and VLDL are LDL 1, beta-VLDL, and Lp(a). Work has been reported implicating various alterations of endothelial function in the permeability of the arterial endothelial barrier in the transport of these low-density, cholesterol-rich macromolecules. Of possibly greater interest is the developing evidence that such proliferation stimulating molecules as platelet-derived growth factor (PDGF) can be produced by a number of cells likely to be involved in the progression of atherosclerotic plaque. In addition to platelets, these include activated monocytes and monocyte derived macrophages, injured endothelial cells, and smooth muscle cells, which can undergo an autocrine conversion to PDGF synthesis--possibly stimulated by LDL from hyperlipidemic serum. Leukotrienes and other endothelium-associated regulatory molecules may also take part in the paracrine and autocrine mechanisms of stimulating smooth-muscle-cell proliferation. Additional recent developments that have led to a better understanding of atherosclerotic pathogenesis have occurred. The first is evidence of the involvement of oxidized LDL and its apolipoprotein B in atherogenesis. Research indicates that antioxidants have a suppressive effect on atherogenesis when oxidized LDL has been involved in lesion development. The data linking the development of autoimmune reactions to these oxidatively altered lipoproteins are also impressive. Further, there is increasing evidence that atherogenesis in nonhuman primates and in people in whom chronic sustained circulating immune complexes are involved is likely to be accelerated, even when few or no classic risk factors are present. These lesions appear to represent a distinct microarchitectural form of concentric and transmural atherosclerosis that is better classified as "atheroarteritis." PMID- 1867234 TI - Rationale for treatment. AB - Based on substantial evidence, the 1984 NIH Consensus Development Conference concluded that the treatment of total and low-density lipoprotein (LDL) cholesterol elevations with diet and, when necessary, with drugs, can reduce the risk of coronary artery disease (CAD). Accordingly, in 1988 the National Cholesterol Education Program (NCEP) published guidelines for defining moderate-, borderline-high-, and high-risk categories for CAD. Many clinical trials have supported the benefits of antihyperlipidemic therapy. Evidence from the Coronary Primary Prevention Trial gave rise to the "2:1 ratio," i.e., that a 1% reduction in total cholesterol level is associated with a 2% decrease in CAD events. The Helsinki Heart Study results indicated that additional benefit may be obtained by raising high-density lipoprotein (HDL)-cholesterol levels. Dramatic reductions in LDL and total cholesterol were achieved by the Program on the Surgical Control of the Hyperlipidemias, which also achieved a 35% reduction in CAD events and a two thirds reduction in both coronary bypass operations and angioplasties. Long-term benefits of cholesterol lowering in terms of cardiovascular and all-cause mortality have been shown in the Coronary Drug Project and the Multiple Risk Factor Intervention Trial. Two major studies that have documented angiographic changes as a result of cholesterol lowering are the Cholesterol-Lowering Atherosclerosis Study (CLAS) and the Familial Atherosclerosis Treatment Study (FATS). In both CLAS and FATS, there was a decrease in the development of new lesions and a lowering of the rate of progression of existing lesions. In FATS, there was also evidence that aggressive antihyperlipidemic therapy will decrease existing lesions in some CAD patients. PMID- 1867235 TI - Alcoholism: the disease and the diagnosis. PMID- 1867236 TI - Alcohol abuse: comparison of two methods for assessing its prevalence and associated morbidity in hospitalized patients. AB - PURPOSE: To evaluate two methods for assessing the prevalence of alcohol abuse in hospitalized patients based upon scores on standardized alcoholism screening instruments compared with diagnostic discharge data, and to determine the risk for comorbid conditions in patients who abuse alcohol. PATIENTS AND METHODS: Of 2,534 consecutive patients admitted to five adult inpatient services of an academic center, 1,964 were screened for alcohol abuse using the CAGE and the SMAST. Their discharge diagnoses were obtained and analyzed for the presence of alcohol-related diagnoses and other comorbid conditions. RESULTS: A total of 1.4% of patients had a principal alcohol-related diagnosis (ARD), 6% had a secondary but no principal ARD, and 15% screened positive for alcohol abuse but had no ARD. The overall prevalence of alcohol abuse was 22.4%. Patients with a principal ARD had a higher risk for dementia, chronic obstructive pulmonary disease (COPD), pancreatitis, sequelae of liver disease, and illegal drug abuse. Patients with a secondary ARD were at risk for 19 comorbid conditions, including pancreatitis, injury, pneumonia, COPD, and poly-drug abuse. Patients who screened positive for alcohol abuse but had no ARD were significantly more likely to have a diagnosis of hypertension, arrhythmia, breast cancer, or pelvic inflammatory disease. CONCLUSION: Discharge diagnoses alone markedly underestimate the prevalence of alcohol abuse in hospitalized patients. Patients from the three groups are at higher risk for comorbid conditions, and secondary prevention of alcohol abuse can be achieved by routinely screening every patient using recognized alcoholism screening instruments. PMID- 1867237 TI - The syndrome of alcoholic ketoacidosis. AB - PURPOSE: To further elucidate the clinical spectrum of alcoholic ketoacidosis (AKA). PATIENTS AND METHODS: A case series of 74 patients with AKA defined as a wide anion gap metabolic acidosis unexplained by any other disorder or toxin, including any patient with a history of chronic alcohol abuse. The setting was the Medical Emergency Department at Grady Memorial Hospital in Atlanta, Georgia, a university-affiliated inner-city hospital. RESULTS: AKA is a common disorder in the emergency department, more common than previously thought. The acid-base abnormalities are more diverse than just a wide-gap metabolic acidosis and often include a concomitant metabolic alkalosis, hyperchloremic acidosis, or respiratory alkalosis. Lactic acidosis is also common. Semiquantitative serum acetoacetate levels were positive in 96% of patients. Elevated blood alcohol levels were present in two thirds of patients in whom alcohol levels were determined, and levels consistent with intoxication were seen in 40% of these patients. Electrolyte disorders including hyponatremia, hypokalemia, hypophosphatemia, hyperglycemia, hypocalcemia, and hypomagnesemia were common on presentation. The most common symptoms were nausea, vomiting, and abdominal pain. The most common physical findings were tachycardia, tachypnea, and abdominal tenderness. Altered mental status, fever, hypothermia, or other abnormal findings were uncommon and reflected other underlying processes. CONCLUSIONS: AKA is a common disorder in chronic malnourished alcoholic persons. The acid-base abnormalities reflect not only the ketoacidosis, but also associated extracellular fluid volume depletion, alcohol withdrawal, pain, sepsis, or severe liver disease. Although the pathophysiology is complex, the syndrome is rapidly reversible and has a low mortality. PMID- 1867238 TI - Pyomyositis in patients with the human immunodeficiency virus: an unusual form of disseminated bacterial infection. AB - PURPOSE AND PATIENTS: Pyomyositis, a common disease in the tropics, is rare in the continental United States, with approximately 83 cases described in the literature in the past two decades. The occurrence of pyomyositis complicating human immunodeficiency virus (HIV) infection has been reported in 10 patients since 1986. We report six cases of this entity in patients with advanced HIV disease seen in our institution over a 20-month period. A common denominator in all of our patients was muscle injury, induced by either exercise or trauma. Unlike most previous reports of HIV-associated pyomyositis, the clinical picture in our cases was complicated by the development of abscesses in multiple muscle groups, requiring prolonged antimicrobial therapy and repeated drainage procedures for successful management. Interestingly, one patient developed concomitant rhabdomyolysis--an otherwise rare event in classical pyomyositis. Staphylococcus aureus was the predominant infecting organism in this as well as all other series. Of note, we also observed and report the first case, to our knowledge, of gram-negative pyomyositis in an HIV-infected individual. The pathogenic implications of this catalase-producing gram-negative isolate are discussed in the context of neutrophil abnormalities in HIV disease. CONCLUSION: Like tropical pyomyositis, its HIV-associated counterpart appears to be multifactorial in origin. Its recent recognition suggests that, in addition to underlying abnormalities of host defense, factors relating to the prolonged survival of patients with late-stage disease, including myopathy, might play an important contributory role. PMID- 1867239 TI - Hepatosplenic candidiasis: successful treatment with fluconazole. AB - PURPOSE: To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment. PATIENTS AND METHODS: Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole. RESULTS: All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis. CONCLUSION: Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy. PMID- 1867240 TI - Fluconazole therapy for chronic disseminated candidiasis in patients with leukemia and prior amphotericin B therapy. AB - OBJECTIVE: To study the efficacy of fluconazole against chronic disseminated candidiasis (hepatosplenic candidiasis) in patients with leukemia in whom amphotericin B treatment had failed. DESIGN: Retrospective analysis of patients with chronic disseminated candidiasis treated with fluconazole on a compassionate investigational new drug protocol. SETTING: Multi-institutional. PATIENTS AND METHODS: Twenty consecutive patients received 100 to 400 mg of fluconazole per day for a median of 30 weeks. All had either failed to respond to treatment with more than 2 g of amphotericin B or had serious amphotericin B-related toxicities. RESULTS: Fourteen of 16 evaluable patients (88%) responded. Responses were observed in seven of nine patients in whom adequate doses of amphotericin B had failed and in all seven patients who had amphotericin B-related toxicities. In 12 patients, cytotoxic chemotherapy was continued without flare of the infection. Fluconazole was well tolerated with rare side effects. Aspergillus superinfection developed in three patients and contributed to the death of two of them. CONCLUSION: Fluconazole is a safe and effective agent with significant activity against chronic disseminated candidiasis. PMID- 1867241 TI - Thiamine deficiency in patients with congestive heart failure receiving long-term furosemide therapy: a pilot study. AB - PURPOSE: To test the hypothesis that long-term furosemide therapy in patients with congestive heart failure (CHF) is associated with clinically significant thiamine deficiency via urinary loss. DESIGN: (1) Biochemical evaluation of thiamine status in hospitalized patients with CHF treated with long-term furosemide and in age-matched control patients. (2) Uncontrolled trial of the effect of intravenous thiamine on cardiac performance in a subset of six patients with CHF. SETTING: General medical ward of a teaching community hospital. PATIENTS: Twenty-three patients with chronic CHF receiving furosemide, and 16 age matched control patients without heart failure and not taking diuretics. Daily furosemide doses were 80 to 240 mg, and duration of furosemide therapy was 3 to 14 months. Patients with identifiable causes of inadequate thiamine intake, absorption, or utilization or increased metabolic requirements were excluded. INTERVENTION: A 7-day course of intravenous thiamine, 100 mg twice daily, in six consenting patients with CHF. RESULTS: A high thiamine pyrophosphate effect (TPPE), indicating thiamine deficiency, was found in 21 of 23 furosemide-treated patients and in two of 16 controls (p less than 0.001). The mean (+/- SE) TPPE (normal: 0% to 15%) in furosemide-treated and control patients was 27.7 +/- 2.5% and 7.1 +/- 1.6%, respectively (p less than 0.001). Despite the high TPPE, the mean (+/- SE) urinary thiamine excretion in the furosemide-treated patients (n = 18) was inappropriately high (defined as greater than 130 micrograms/g creatinine), 410 +/- 95 micrograms/g creatinine, even in comparison with that in the controls (n = 14): 236 +/- 69 micrograms/g creatinine. In six patients treated with intravenous thiamine, the elevated TPPE decreased to normal, from a mean (+/- SE) of 27.0 +/- 3.8% to 4.5 +/- 1.3% (p less than 0.001), indicating normal thiamine utilization capacity. Left ventricular ejection fraction increased in four of five of these patients studied by echocardiography. CONCLUSIONS: These preliminary findings suggest that long-term furosemide therapy may be associated with clinically significant thiamine deficiency due to urinary loss and contribute to impaired cardiac performance in patients with CHF. This deficit may be prevented or corrected by appropriate thiamine supplements. PMID- 1867242 TI - Risk factors for stroke in patients with nonrheumatic atrial fibrillation: a case control study. AB - PURPOSE: Randomized controlled trials have demonstrated that anticoagulant therapy is very effective at preventing stroke among patients with nonrheumatic atrial fibrillation. However, these trials have reported too few strokes for powerful risk factor analysis. Observational studies may provide additional information. The purpose of this study was to identify risk factors in a larger number of patients with stroke and nonrheumatic atrial fibrillation, using case control methodology. PATIENTS AND METHODS: We identified all patients discharged from one hospital over an 8-year period who met our case definition of nonrheumatic atrial fibrillation and ischemic stroke (n = 134), and compared them with contemporaneous control subjects who were discharged with nonrheumatic atrial fibrillation without stroke (n = 131). RESULTS: Cases and controls were similar in terms of duration of atrial fibrillation; proportion with paroxysmal atrial fibrillation; percentage with a past medical history of angina, myocardial infarction, congestive heart failure, diabetes, or smoking; and mean left atrial size. In contrast, cases were significantly older than controls (78.5 versus 74.8 years, p = 0.002) and more likely to have a history of hypertension (55% versus 38%, p = 0.0093). The relative odds for stroke was 1.91 for patients with hypertension, 1.73 for patients older than 75 years, and 3.26 for patients with both factors. CONCLUSIONS: Our analysis suggests that age and hypertension should be considered when deciding upon long-term anticoagulant therapy to prevent stroke in patients with nonrheumatic atrial fibrillation. PMID- 1867243 TI - Syncope and orthostatic hypotension. AB - PURPOSE: The purpose of this study was to determine the postural blood pressure response over time, the prevalence of orthostatic hypotension in patients with syncope, and the relationship of orthostatic hypotension to recurrence of symptoms. PATIENTS AND METHODS: We prospectively evaluated 223 patients with syncope in a standardized manner. Orthostatic responses were measured in a standardized fashion at 0, 1, 2, 3, 5, and 10 minutes or until symptoms occurred. Follow-up was obtained at 3-month intervals. Causes of syncope were assigned by predetermined criteria. RESULTS: Orthostatic hypotension (20 mm Hg or greater systolic blood pressure decline) was found in 69 patients (31%). The median time to reach minimal standing systolic blood pressure was 1 minute for all subjects. In patients with orthostatic hypotension (20 mm Hg or greater), mean time to reach minimum blood pressure was 2.4 minutes. The vast majority of patients with significant orthostatic hypotension had this finding within 2 minutes of standing. Orthostatic hypotension was common in patients for whom other probable causes of syncope were assigned. The recurrence of syncope was not related to the degree of orthostatic hypotension; however, the recurrence of dizziness and syncope as end-points was lower in patients with 20 mm Hg or greater systolic blood pressure reductions as compared with patients with lesser degrees of orthostatic blood pressure declines. CONCLUSION: Orthostatic hypotension is common in patients with syncope and is detected in the vast majority of patients by 2 minutes. Although symptom recurrence on follow-up was lower in patients with more severe orthostatic hypotension, the clinical significance of this finding needs to be further defined by future studies. PMID- 1867244 TI - Eosinophiluria in atheroembolic renal disease. AB - PURPOSE AND PATIENTS: Eosinophiluria has been reported in acute interstitial nephritis and other renal diseases, but its presence in atheroembolic renal disease (AERD) has not been previously established. AERD has been identified as a cause of acute and chronic renal failure, particularly in elderly patients with advanced atherosclerosis and in those patients who have undergone manipulation or intervention of the abdominal aorta, renal artery, or coronary artery. The definitive diagnosis is made by renal biopsy. However, many patients are too acutely ill to tolerate renal biopsy and, in recent years, peripheral eosinophilia, hypocomplementemia, and thrombocytopenia have been recognized in association with AERD. Previous studies have reported that AERD is associated with an inactive renal sediment and an absence of urine eosinophils. We reviewed our experience over a 4-year period with 24 patients with renal biopsy-proven AERD. RESULTS: Urine eosinophils were evaluated in nine patients to help determine the cause of their renal deterioration. Seven of these patients presented with evidence of vascular disease. Three patients had procedures involving manipulation of the abdominal aorta. Physical examination revealed findings of atheroembolism in three of nine patients. Overall, eight of nine patients had a positive Hansel's stain for eosinophiluria. Six of eight patients had more than 5% of their urinary white cell count as eosinophils. The reason for failure of previous studies to detect eosinophiluria in AERD is unclear but may have been related to the use of Wright's stain instead of Hansel's stain. CONCLUSION: In the evaluation of acute renal insufficiency, eosinophiluria may indicate AERD in addition to the other known causes for this finding. PMID- 1867245 TI - Sleep apnea and systemic hypertension: a causal association review. AB - OBJECTIVE: To critically examine the causal association between sleep apnea syndrome and hypertension. METHODS: A retrospective systematic critique of five epidemiologic studies published in the English literature during 1978 to 1989 identified on Medline and manual literature searches. The evidence was evaluated using the standard observational criteria for causation: strength of association, consistency, dose-response relationship, temporal sequence, specificity, and biologic plausibility. RESULTS: We found evidence to support a causal association between sleep apnea syndrome and hypertension in consistency and specificity and some evidence to suggest a dose-response relationship. Review of the data dealing with the mechanisms important in the pathogenesis of sleep apnea and hypertension allowed us to advance several theories to provide support for biologic plausibility. CONCLUSION: We concluded that there is a positive association- relative risk estimate between 1.3 and 40--for sleep apnea syndrome and hypertension, but the risk association is unstable. Thus, we believe that there is insufficient data to justify doing polysomnography as part of the routine diagnostic work-up for patients with hypertension. PMID- 1867246 TI - Congenital bronchiectasis in an adult. PMID- 1867247 TI - Excessive salivation as an anginal equivalent: a sequela to Ramsay Hunt syndrome. PMID- 1867248 TI - Pasteurella multocida: zoonotic cause of peritonitis in a patient undergoing peritoneal dialysis. PMID- 1867249 TI - Psittacosis-associated hemophagocytic syndrome. PMID- 1867250 TI - Effects of sulindac on renal prostaglandins and glomerular filtration rate. PMID- 1867251 TI - High-risk etiology as a predictor of a complicated course in community-acquired pneumonia. PMID- 1867252 TI - Unique phenotype associated with a pericentric inversion of chromosome 6 in three generations. AB - We observed a pericentric inversion of chromosome 6 in three generations of one family. Carriers had several phenotypic alterations including congenital cataracts, hearing loss, dental anomalies, ear anomalies, premature graying, unilateral strabismus, coloboma, and mild mental retardation. These manifestations may all be explained by a failure or delay in development of tissues derived from neural crest cells and are similar to these seen in the Rieger syndrome. The description of this family extends the known phenotypic abnormalities associated with alterations of chromosome 6. PMID- 1867253 TI - Holoprosencephaly in a newborn girl with 46,XX,i(18q). AB - We report on a newborn girl with holoprosencephaly, microcephaly, absent right radius, and other anomalies with an 46,XX,i(18q) chromosome constitution. This is the first report of an i(18q) in syndromal alobar holoprosencephaly. PMID- 1867254 TI - Macrostomia, ectropion, atrophic skin, hypertrichosis: another observation. AB - We report on a boy with bilateral ectropion, ocular hypertelorism, bulbous nose, macrostomia with thin lips, abnormal ears, hypertrichosis of the forehead, neck and back, atrophic skin with hypoplastic nipples. Cause and inheritance are unknown. PMID- 1867255 TI - Treacher Collins-Franceschetti syndrome with tracheoesophageal fistula, rectovaginal fistula, and anal atresia: variant, or new syndrome? PMID- 1867256 TI - Prenatal diagnosis of hereditary amyloidosis in a Portuguese family. AB - Portuguese-type amyloidosis is an autosomal dominant condition caused by a point mutation of the prealbumin (transthyretin) gene. The mutation can be detected directly by the presence of a restriction site for Nsil. We report the first prenatal diagnosis for this condition, performed in the first trimester by chorionic villus sampling, polymerase chain reaction, and restriction enzyme digestion. PMID- 1867257 TI - Maternal muscle biopsy in X-linked recessive centronuclear (myotubular) myopathy. AB - Muscle biopsy was used to attempt determination of carrier status in mothers and maternal relatives of patients with severe neonatal centronuclear (myotubular) myopathy, an X-linked recessive disorder. We report findings from muscle biopsies of 3 mothers, one an obligate carrier. All biopsies showed abnormalities of nonspecific character. Whether such abnormalities assist in defining carrier status is uncertain. A more specific tissue marker for this disorder is required before muscle biopsy will facilitate carrier identification. PMID- 1867258 TI - Lethal congenital muscular dystrophy with cataracts and a minor brain anomaly: new entity or variant of Walker-Warburg syndrome? AB - A term newborn male with severe hypotonia and contractures was found to have dense bilateral cataracts. He died at age 3 days of respiratory failure. Amino acidopathies and disorders of peroxisome function were excluded, and results of serologic studies and placental histopathology, specifically seeking evidence of intrauterine infection, were normal. Autopsy showed changes in the skeletal muscles consistent with congenital muscular dystrophy and a small focal anomaly of the cerebral cortex. These findings either represent a new syndrome or raise further questions about broadening the spectrum of known congenital muscular dystrophy syndromes with associated eye and brain anomalies. PMID- 1867259 TI - Sirenomelia and anencephaly. AB - We report on a monozygotic twin with sirenomelia and anencephaly. This association seems to have been observed only twice before. In addition to these anomalies the patient had cleft palate, rachischisis, and segmentation vertebral anomalies affecting the cervical and the upper thoracic spine. The second twin was a liveborn female infant with a large cystic paraovarian teratoma, and duplication of internal genitalia. PMID- 1867260 TI - Characterization of the calcitonin/CGRP gene in Williams syndrome. AB - We have investigated the possibility of mutations in the calcitonin/calcitonin gene related peptide (CGRP) gene in children with Williams syndrome. Involvement of the calcitonin/CGRP gene in Williams syndrome is postulated on the basis that Williams syndrome children often have infantile hypercalcemia and deficient expression of calcitonin, a hormone that lowers serum calcium levels. To test the hypothesis that mutations in the calcitonin/CGRP gene might be responsible for the reduced calcitonin levels, we examined the calcitonin/CGRP gene structure in Williams syndrome children. Analysis of white blood cell DNA by Southern blot hybridizations in 5 individuals did not show any detectable large deletions or rearrangements in the calcitonin/CGRP gene locus. The possibility of small deletions or point mutations within the exon encoding the mature calcitonin hormone is unlikely based on ribonuclease protection assays with patient DNA amplified by the polymerase chain reaction (PCR) technique. These findings suggest that the calcitonin deficiency might be due either to mutations elsewhere in the gene or to defects in the cellular machinery needed for calcitonin synthesis and/or secretion. PMID- 1867261 TI - Bartsocas-Papas syndrome: three familial cases from Spain. AB - We report on 3 Spanish sibs with the Bartsocas-Papas syndrome. This appears to be the seventh reported family; all but one of them are of Mediterranean origin. We propose that a generalized vascular disruption is the most likely pathogenetic mechanism for the anomalies found in this syndrome. PMID- 1867263 TI - Metaphyseal anadysplasia: a metaphyseal dysplasia of early onset with radiological regression and benign course. AB - We report on 4 boys (including 2 maternally related first cousins) with a metaphyseal dysplasia of early onset and regressive evolution. Diagnosis is possible in the first months. Distal metaphyses of long bones are very irregular. Femoral necks seem hypoplastic and the edges of the metaphyses are almost vertical; femoral shaft is bowed. Those anomalies disappear after 2 years. The main manifestations are slight shortness and a light varus deformity of the lower limbs. Stature is not affected. The upper tibial growth cartilage, studied in one case, showed wide proliferative and hypertrophic zones with an unusual appearance of the last hypertrophic cells and an abnormal zone of cartilage calcification and resorption. The name "metaphyseal anadysplasia" is suggested for this early and regressive disorder. We are aware of other forms of regressive metaphyseal dysplasia which deserve further delineation. Therefore infants whose radiological changes of metaphyseal dysplasia do not fall into one of the well-defined types should be followed and prediction of the adult height should not be made on the basis of the findings on the initial examination. PMID- 1867262 TI - Screening of male patients with autosomal recessive Duchenne dystrophy through dystrophin and DNA studies. AB - Previously we estimated that about 2.5-4% of isolated male patients diagnosed as Duchenne dystrophy (DMD) may have the autosomal recessive form (AR-DMD). Such cases can be distinguished from X-linked DMD through the analysis of dystrophin. Fifty DMD patients from 47 families were investigated for dystrophin and DNA deletions. Based on our results, we estimate that the frequency of AR-DMD may be about 8-12% among male patients diagnosed as DMD in whom X-linked inheritance could not be confirmed through pedigree data, serum enzymes in female relatives or DNA studies. Such an estimate must be confirmed in a larger sample; however, it shows the importance of assessing dystrophin in all patients diagnosed as DMD in whom X-linked inheritance cannot be proved, since the distinction between these 2 forms has implications for genetic counseling. PMID- 1867264 TI - 45,X/47,XYY mosaicism: clinical discrepancy between prenatally and postnatally diagnosed cases. AB - 45,X/47,XYY mosaicism is a rare chromosomal disorder with clinical information limited to 11 postnatal cases in the literature and with uncertainty regarding prenatal prediction of phenotype and prognosis. We report on 7 new cases of 45,X/47,XYY mosaicism, three detected prenatally and 4 diagnosed postnatally. A clinical comparison of the cases of 45,X/47,XYY mosaicism is presented together with a literature review. PMID- 1867265 TI - CHARGE association: clinical manifestations and developmental outcome. AB - Mental retardation and growth failure are considered integral manifestations in the CHARGE association, reported to be present in as many as 90% of cases. Recent studies have reported a better than expected outcome in some patients; however, the conclusions of these studies have been confounded to some extent by their inclusion criteria. We report follow-up of 17 patients with CHARGE association in whom the diagnosis was based on clinical findings present in early infancy, before developmental patterns were established. Of the 7 survivors, all had motor delay, and 6 had feeding difficulties during infancy. Psychometric assessment at follow-up (age range 2 years, 10 months, to 15 years) showed that 2 were functioning in the normal range, 3 had specific language delay, one had moderate mental retardation, and one had severe mental retardation. Feeding problems persisted in only the 2 youngest patients. After initial failure to thrive, normal height was reached in 4 of 5 children older than age 3 years. The effects of visual and hearing deficits, their management, and the effects of physical illness are discussed with respect to developmental outcome. Our results suggest that some infants with CHARGE association who survive early infancy have a better prognosis for feeding difficulties, growth, and mental development than may be expected from early performance and better than that generally predicted from the current literature. The prompt management of sensory deficits is emphasized. PMID- 1867266 TI - Deletion of 20p 11.23----pter with normal growth hormone-releasing hormone genes. AB - Using a molecular analysis of the DNA from a patient with a deletion of chromosome 20 [46,XX,del(20)(p 11.23)], we have excluded the growth hormone releasing hormone (GHRH) gene from the region 20p11.23----pter. The patient had minor facial anomalies. Rieger eye anomaly, a congenital heart defect, severe failure to thrive, and a neurosecretory problem in growth hormone (GH) secretion. Since the GHRH gene was previously mapped to chromosome 20, we used molecular genetic methods to determine whether the growth abnormalities were due to the deletion of this gene. DNAs of the patient and 2 normal control subjects were analyzed by quantitative Southern blotting using a DNA probe for the GHRH gene and 2 reference DNA probes mapping to chromosome 21. The GHRH gene was found to be present in 2 copies in the patient. This indicates that the gene for GHRH maps to the region outside the patient's deletion, in 20p11.23----qter. Furthermore, our results suggest that genes other than GHRH on 20p are important for developmental steps leading to normal neurosecretory function of GH and may also be involved in generating Rieger eye anomaly. Finally, GH deficiency and Rieger eye anomaly should be sought in other patients with deletions of 20p. PMID- 1867267 TI - Three years' experience with neonatal screening for Duchenne/Becker muscular dystrophy: gene analysis, gene expression, and phenotype prediction. AB - Neonatal screening for Duchenne/Becker Muscular dystrophy (DMD/BMD) was begun as a pilot program on January 1, 1986. The aim of this program was to reduce the incidence of this X-linked recessive degenerative neuromuscular disease. The neonatal detection of a boy with DMD allows early identification of carriers and genetic counselling. This may avert the birth of other affected males born prior to clinical diagnosis of DMD in the propositus at about age 5 years. Between January 1, 1986, and December 31, 1988, we identified and characterized a cohort of 8 asymptomatic infant boys with grossly elevated levels of creatine kinase, an active primary dystrophic process of muscle and complete dystrophin deficiency. Five of 8 males have detectable DNA alterations involving the DMD/BMD locus. Based on current hypotheses, characterization of dystrophin expression of this cohort allows us to predict a DMD phenotype in all 8 boys. To date, no additional males with DMD have been born in these families. Prospective follow-up will allow us to test the validity of dystrophin testing in predicting the clinical course and impact of this program on reproductive decision making in these families. PMID- 1867268 TI - Teebi hypertelorism syndrome (brachycephalofrontonasal dysplasia) in a U.S. family. AB - Teebi (Am J Med Genet 28:581-591, 1987) described a pattern of anomalies in an Arab kindred involving 16 individuals in 4 generations. Although some findings were similar to those in craniofrontonasal dysplasia, absence of craniosynostosis, normal to slightly broad nasal tip, normal nails, and male to male transmission distinguished this as a separate entity. This paper describes a U.S. family with similar findings, involving 6 individuals (2 male and 4 female) in 4 generations, with male to male transmission. PMID- 1867269 TI - Biochemical and genetic analysis of a child with cystic fibrosis and cystinosis. AB - We have studied a child with cystic fibrosis (CF), nephropathic cystinosis, and manifestations of Bartter syndrome, a finding reported previously in both of these diseases (CF and cystinosis). The chance of an individual inheriting a mutant allele for both CF and cystinosis from each of his parents by independent segregation is very small. Therefore, other mechanisms of inheritance were investigated, including whether his diseases were caused by a chromosome deletion or rearrangement that caused defects in both genes, whether his phenotype was caused by a new mutation or variant of either disease, or whether both diseases were inherited together due to inheritance of 2 copies of the same chromosome from one of the parents (uniparental disomy). An investigation was made of whether having mutations for both CF and cystinosis resulted in a different phenotype for either disease and whether the child was a heterozygote rather than a homozygote for one of the mutations. The results suggest that neither disease influenced the expression of the defect in the other and that this child inherited a mutant allele for both diseases independently from each parent. PMID- 1867270 TI - Familial congenital micromelic dysplasia with dislocation of radius and distinct face: a new skeletal dysplasia syndrome. AB - Recently Maroteaux et al. [Am J Med Genet 32:371-375] described omodysplasia as a new distinct congenital bone disorder in 3 cases; autosomal dominant inheritance was suggested. In this same report, 2 other cases (patients 4 and 5) presented with the same facial and upper limb anomalies, but were also noted to have severe shortness of lower limbs. The authors considered all 5 cases to represent variable expressivity of the same disorder, namely, omodysplasia. Here we report 4 patients (3 survivors), offspring of consanguineous Arabic-Moslem couples. All presented at birth with severe short limb dwarfism and facial and radiologic appearance quite distinct from the first 3 patients of Maroteaux et al. [1989] with so-called omodysplasia. Thus, we suggest that our 4 cases and patients 4 and 5 of Maroteaux et al. [1989] represent a distinct, previously unpublished bone dysplasia. PMID- 1867271 TI - Sex chromosome marker: clinical significance and DNA characterization. AB - Two patients are described with a virtually identical marker sex chromosome that was so small as to defy classification by conventional cytogenetic studies. DNA hybridization with Y probes allows classification into Y or non-Y, and in situ hybridization with X centromere specific sequences, into X or non-X. One patient was proven to have a Y fragment, and the second, an X fragment. DNA characterization is important since prognosis and clinical management depends on proper identification of the small marker sex chromosome. PMID- 1867272 TI - Short rib syndrome Beemer-Langer type with polydactyly: a multiple congenital anomalies syndrome. AB - A male fetus with short rib (polydactyly) syndrome, Beemer-Langer type was aborted at 30 weeks' gestation because of abnormalities visualized on sonography. This is the first documented case with polydactyly in this recently defined entity. The clinical, radiological, and pathological findings, especially of the bones, are described. The differential diagnosis of this entity is discussed. PMID- 1867273 TI - Beemer-Langer syndrome with manifestations of an orofaciodigital syndrome. AB - We report on an infant girl with hydrops, macrocephaly, high forehead, flat face, hypertelorism, broad nasal bridge, median cleft lip and alveolar ridge, grooved palate, accessory frenula, small tongue, milia, severe rib and limb shortness, brachydactyly, talipes equinovarus, Dandy-Walker malformation, accessory spleen, unfixed mesentery, ectopic pancreas, and renal cysts. This patient resembles seven previously reported patients with the Beemer-Langer syndrome, a distinct lethal short rib syndrome characterized by hydrops, markedly short ribs and limbs, median cleft lip with or without cleft palate, flat face, and macrocephaly. Polydactyly is usually absent. Our patient's oral anomalies suggest an orofaciodigital syndrome, but the severe rib and limb shortness distinguish it from those disorders. PMID- 1867274 TI - Renal dysgenesis in a monozygotic twin: association with in utero exposure to indomethacin. AB - We report oligohydramnios and renal dysgenesis in one of identical twins, which might have resulted from in utero exposure to early, prolonged high-dose indomethacin. The proposita was the second of twin girls born at 36 weeks of gestation. Pregnancy was complicated initially by polyhydramnios in both amniotic sacs and premature uterine contractions. After administration of indomethacin and terbutaline from 16 to 30 weeks' gestation, serial prenatal ultrasound examinations ultimately showed oligohydramnios in twin B and resolution of polyhydramnios in twin A. On day 5 twin B developed hematuria, hypertension, renal failure, hyponatremia, hyperkalemia, metabolic acidosis, sodium wasting and severe, transient inability to excrete potassium. Renal sonography showed enlarged, hyperechoic kidneys with almost no corticomedullary differentiation. Renal biopsy revealed immature glomeruli, dilated Bowman's spaces, dilated tubules, and interstitial fibrosis. The liver was histologically normal. Indomethacin may induce oligohydramnios and transient renal insufficiency in humans and renal dysgenesis in fetal monkeys; it might have induced the abnormalities in this patient. PMID- 1867275 TI - Duplication of the distal part of the long arm of chromosome 1. AB - A case of dup(1)(q42----qter) is reported. A literature review of duplication of the distal third of chromosome 1 with breakpoints at various sites, 1q23, 1q25, 1q32, and 1q42, was undertaken. Clinical similarities and differences based on the size of the duplicated segment and other associated deficiencies are summarized. PMID- 1867276 TI - Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Stanford Lipid Research Clinics Family Study. AB - We examined the familial aggregation of lipids [total cholesterol (CH) and triglyceride (TG)] and lipoproteins [high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL)] in families ascertained through random and nonrandom probands in the Stanford Lipid Research Clinics Family Study. Nonrandom probands were selected because their lipid levels at a prior screening visit exceeded a certain prespecified threshold. The statistical method is based on selection through indirect truncation on a correlated trait (in which the likelihood function is conditioned on the actual event that the proband's value is beyond the threshold). This method allows for estimation of the path model parameters in randomly and nonrandomly ascertained families jointly and separately, thus enabling tests of heterogeneity between the two types of samples. The results suggest that the multifactorial transmission is homogeneous in the random and hyperlipidemic samples for CH. However, the evidence for heterogeneity is moderate for LDL, marked HDL, and mixed for TG. The general pattern of observed results is for somewhat higher genetic heritabilities in the random than nonrandom samples, which is compatible with a higher prevalence in the random sample of certain dyslipoproteinemias associated with nonelevated lipids. Substantial genetic heritability is found for CH, HDL, and LDL, with somewhat lower estimates for TG. Cultural heritability is low but significant for all four traits. Little or no spouse resemblance or nontransmitted shared sibship effects are seen. In contrast to the findings from previous studies, little or no parental cultural transmission is seen. PMID- 1867277 TI - Using OMIM (On-line Mendelian Inheritance in Man) as an expert system in medical genetics. AB - Expert systems have been used in Medicine for many years, but they are usually highly sophisticated and not well integrated into day-to-day practice. On the other hand, bibliographic databases such as Medline and others are easily accessible and are widely used. We report here the use of OMIM (On-line Mendelian Inheritance in Man), one of these bibliographic databases, as an expert system in Medical Genetics. The description of 93 syndromes was used as search-key and the diagnoses proposed by OMIM were analyzed to determine whether the correct diagnosis was among them. The proposed diagnoses were automatically ranked by OMIM from the most probable (weight = 100) to the least probable (weight = 1). OMIM suggested a total of 1538 +/- 692.2 diagnoses per search. In order to deal with a reasonable number of proposed diagnoses, we only considered the diagnoses with a weight of 50 or more. With this limit, OMIM proposed a mean of 37.0 +/- 24.6 diagnoses per case. The overall accuracy was 76%. A correct answer with a perfect weight of 100 was proposed in 29% of the case. The diagnostic accuracy of OMIM increased linearly when weights lower than 100 were considered. When the rank alone was analyzed, the accuracy of OMIM increased very rapidly from position 1 to 5 with a subsequent almost linear increase. If one only considered the first five proposed diagnoses, the accuracy of OMIM was just above 50%. This study shows that bibliographic databases are not only restricted to the provision of references but could also be used as expert systems and are therefore of great value to medical geneticists. PMID- 1867278 TI - Two forms of ring 13 in a child with rhabdomyosarcoma. AB - Mosaicism for two forms of ring 13 was found in a child with embryonal rhabdomyosarcoma of the bladder, minor anomalies, and developmental delay. Her chromosome constitution was 46,XX,r(13)(p11q34)/46,XX,r del(13)(p11q14). Both cell lines were present in lymphocytes and fibroblasts. The cell line with the smaller ring chromosome predominated in both tissues. The child's manifestations reflect the presence of both cell lines. PMID- 1867280 TI - Dandy-Walker malformation (variant), cystic dysplastic kidneys, and hepatic fibrosis: a distinct entity or Meckel syndrome? AB - Dandy-Walker malformation is an unusual finding in Meckel syndrome, which characteristically presents with encephalocele, polydactyly, and cystic renal disease. We report on a family in which three nonviable brothers had Dandy-Walker malformations (variant) with associated enlarged cystic dysplastic kidneys and hepatic fibrosis. The consistent segregation of these abnormalities in all three sibs in the absence of polydactyly and encephalocele suggested the possibility of a distinct syndrome. The clinicopathological findings of the disorder are described and discussed in the context of the phenotypic spectrum of Meckel syndrome. PMID- 1867279 TI - Deletion mapping of a retinal cone-rod dystrophy: assignment to 18q211. AB - Deletion of 18q211 was observed in a mentally retarded young man with electrophysiologically demonstrated cone-rod dystrophy, present since childhood. He had hypogonadism and a central postsynaptic hearing impairment. This is the first case of a chromosome deletion in a patient with a cone-rod dystrophy. Three patients with more distal deletions on chromosome 18 did not present retinal dystrophies. We suggest that one of the loci for cone-rod dystrophy may be located on chromosome 18 at q211-213. Reports of similar findings will be necessary for confirmation of this assumption. PMID- 1867281 TI - Using log-linear models to test for associations among congenital malformations. AB - Log-linear models can be used to test for pairwise associations and higher order interactions among anatomically distinct birth defects or congenital malformations. A log-linear model, including terms for every possible pairwise association among seven severe and easily detectable congenital malformations, was examined using data on 16,217 infants registered in the Metropolitan Atlanta Congenital Defects Program between 1968 and 1986. The resulting model showed clear patterns of strong association between some congenital malformations and not others, and the presence of 3-way interaction terms where the association between two malformations depended on the presence of a third. Examining a more parsimonious log-linear model showed overlapping patterns of pairwise association involving anal-rectal atresia and omphalocele, anal-rectal atresia and limb deficiency, and anal-rectal atresia and tracheaesophageal fistula. A second common pattern involved a triangular cluster with a hierarchical relationship among the three malformations (where there was a strong association between the first and second malformations and between the first and third malformations, but the association between the second and third was only seen in the absence of the first). Three such overlapping triangular clusters were identified from these data: neural tube defects, oral clefts, and omphalocele; neural tube defects, oral clefts, and limb deficiency; and limb deficiency, diaphragmatic hernia, and neural tube defects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867283 TI - Postmortem chorionic villus sampling: correlation of cytogenetic and ultrasound findings. AB - We performed chorionic villus samplings (CVS) in 795 cases in the first trimester during a 13-month period. Of these 35 were found to have a blighted ovum or missed abortion prior to the procedure. Nineteen women consented to have CVS. Ultrasonographic and cytogenetic findings in these 19 pregnancies were correlated. Expected gestational age was determined by last menstrual period. Observed gestational age was determined by crown rump length (CRL) (12 pregnancies) or gestational sac (GS) (7 pregnancies without fetal pole). The differences in days between the estimated and observed gestational ages was determined for each pregnancy. In all 19 CVS samples cytogenetic diagnosis documented aneuploidy. Ten cases had chromosome abnormalities virtually always lethal in the embryonic period (group I). Nine pregnancies had defects with moderate potential for fetal viability (group II). Gestations with low viability potential (group I) had estimated minus observed gestational age discrepancies (23.4 +/- 8.3 days) significantly greater than gestations with moderate viability potential (group II) (8.9 +/- 4.3 days) (P less than .001). The absence of a fetal pole was more common in group I. CVS in pregnancies with missed abortion or blighted ovum is feasible and has a high likelihood of documenting aneuploidy. Furthermore, the more severe the anomaly the more likely there will be very early fetal demise or intrauterine growth retardation. PMID- 1867282 TI - Family with 22-derived marker chromosome and late-onset dementia of the Alzheimer type: I. Application of a new model for estimation of the risk of disease associated with the marker. AB - We have identified 2 sisters with probable dementia of the Alzheimer type who have an unusual 22-derived marker chromosome with a greatly elongated short arm containing 2 well-separated nucleolus organizer regions. A marker chromosome similar in appearance is uncommon in the general population. Eleven of 24 of their biological relatives were also found to have the marker. The known pedigree of this family encompasses 6 generations in 2 of which there is evidence of 10 cases of dementia of the Alzheimer type. The average age-at-onset of dementia is 65.8 +/- 5.5 years; the average age-at-death among those apparently affected is 74.9 +/- 8.3 years. A new model for the estimation of risk was applied to the family data. Persons in this family with the marker were found to be 4 times more likely to develop dementia than those without the marker, the 95% confidence interval for this risk being 1-50. The probability that the association of dementia and the marker is due to chance alone is .05 (1 in 20). PMID- 1867284 TI - Molecular characterization of severe alpha-thalassemias causing hydrops fetalis in Taiwan. AB - alpha-Thalassemia hydrops fetalis is a common disorder in Taiwan. The condition causes perinatal death and many maternal obstetrical complications. In order to determine the molecular defects of this condition in Chinese, 87 unrelated families with this disorder were collected in the past 4 years. The molecular defects were studied by Southern blotting and DNA hybridization with phi zeta 1 globin gene and LO (a 0.4 kb BamHI/EcoRI fragment in the 5' flanking region of the zeta 2-globin gene) probes. Eighty-one (93.1%) fetuses had homozygous Southeast Asian deletion (- -SEA/- -SEA). Five (5.7%) fetuses were compound heterozygotes for the Southeast Asian deletion and Thailand deletion (- -SEA/- THAI). The remaining fetus was a compound heterozygote for the Southeast Asian deletion and an uncharacterized nondeletional defect (- -SEA/(alpha alpha)Th). The molecular defects of alpha-thalassemia hydrops fetalis in Chinese are heterogeneous. This fact has important implications for genetic counseling and prenatal diagnosis. PMID- 1867285 TI - Distribution of aneuploidy in human gametes: comparison between human sperm and oocytes. AB - The frequency and distribution of aneuploidy was compared in 11,615 karyotyped human sperm and 772 karyotyped human oocytes to determine if all chromosomes are equally likely to be involved in aneuploid events or if some chromosomes are particularly susceptible to nondisjunction. The frequency of hypohaploidy and hyperhaploidy was compared among different chromosome groups and individual chromosomes for human sperm and oocytes. In general, hypohaploid chromosome complements were more frequent than hyperhaploid complements, in sperm and oocytes. The distribution of chromosome loss in the hypohaploid complements indicated that significantly fewer of the large chromosomes and significantly more of the small chromosomes were lost, suggesting that technical loss predominantly affects small chromosomes. A conservative estimate of aneuploidy (2 X hyperhaploidy) was approximately 3-4% in the human sperm and 18-19% in human oocytes. All chromosome groups were represented among hyperhaploid human sperm and oocytes. For human sperm, the observed frequency of hyperhaploidy equaled the expected frequency based on the assumption that the frequency of nondisjunction is equal for all chromosome groups, with two exceptions: group G and the sex chromosomes. Among individual chromosomes in human sperm, chromosomes 1 and 21 and the sex chromosomes had a significant excess of hyperhaploidy. For human oocytes, there were fewer hyperhaploid oocytes than expected for chromosome groups C and F and more than expected for chromosome groups D and G. Among individual chromosomes there was a significant excess for chromosome 21. These results indicate that all chromosomes are susceptible to nondisjunction but that chromosome 21 is particularly prone to aneuploidy in both human sperm and oocytes. They also demonstrate that sex chromosome aneuploidy is common in human sperm but not in human oocytes. PMID- 1867286 TI - Pseudo-trisomy 13 syndrome. AB - We have coined the term "pseudo-trisomy 13 syndrome" to designate cases of holoprosencephaly, severe facial anomalies, postaxial polydactyly, various other congenital defects, and normal chromosomes. Eleven instances are summarized. Two pairs of sibs and two other cases with consanguinity suggest autosomal recessive inheritance. Autosomal recessive inheritance is possible. Alternately, an undetected microdeletion and etiologic heterogeneity (some cases possibly representing dominant new mutations) must be considered. Further delineation is necessary. It is hoped that this paper will serve as a focus for further discussion of the problem. PMID- 1867287 TI - New clinical aspects of hereditary mucoepithelial dysplasia. AB - Hereditary mucoepithelial dysplasia (HMD) is a multiepithelial disorder. It is transmitted as an autosomal dominant trait (McKusick: Mendelian Inheritance in Man-Catalogs of Autosomal Dominant, Autosomal Recessive, and X-Linked Phenotypes, 8th edition. Baltimore: The Johns Hopkins University Press, pp 499, 1988). HMD is characterized by variable combinations of lesions of skin, hair, orificial mucosa, gingiva, eyes, and lungs. In some previously described patients, the corneal and pulmonary lesions were progressive and led to blindness, recurrent pneumonia, and/or premature death. On light microscopy, the lesion is characterized by dyskeratosis, and, on electron microscopy, by a paucity of gap junctions and desmosomes. Here, we describe a new 5-generation kindred in which affected individuals had the same histologic characteristics but a somewhat different clinical spectrum and a more benign course. HMD should be considered in the differential diagnosis of childhood alopecia, follicular hyperkeratosis, keratoconjunctivitis, juvenile cataracts, gingival hyperemia, restrictive lung disease, and esophageal stenosis or webs. PMID- 1867288 TI - Syndrome: le mot de jour. AB - Syndrome is one of the oldest terms in the medical vocabulary. It has been used as a designation for those disorders that were marked by etiologically nonspecific similar groups of manifestations up to the time of Syndenham. His contention that the terms syndrome and disease were in fact synonymous explains in part infrequent use of syndrome in the literature until the latter part of the 19th century. Redefinition of syndrome early in the 20th century as a disorder characterized by the concurrence of symptoms which are causally related, and further refinement of the definition as a condition marked by a cluster of symptoms occurring together coincidentally, gradually restored the popularity of the term to where syndrome is now one of the most frequently used designations of morbid states in the literature. There are numerous definitions of syndrome currently in use. One which is accepted by most dysmorphologists, geneticists, and some clinicians states that syndrome is an etiologically defined entity of unknown pathogenesis. However, most writers use the term randomly to denote any abnormal condition, whether medical, social, or behavioral, when a more satisfactory designation cannot be found or created, or to emphasize special complexity (syndromic qualities?) of already named diseases, or merely to be amusing. The post-Sydenham custom of naming of syndromes after physicians gave way in the mid-20th century to methods wherein syndrome names incorporate clinical, etiological, genetic, and other significant characteristics. Other methods used in designating syndromes include using the names of the first patient known to be affected, acronyms and abbreviations, personal names of all kinds, and the like.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867289 TI - Duty to disclose in medical genetics: a legal perspective. AB - As technical knowledge and public information in medical genetics continue to expand, the geneticist may expect to be held responsible for informing patients and clients about new developments in research and diagnosis. The long legal evolution of the physician's duty to disclose, and more recent findings of a physician's duty to recall former patients to inform them about newly discovered risks of treatment, indicate that medical geneticists may have a duty to disclose both current and future information about conditions that are or could be inherited. Recent case law supports findings of professional liability for both present and future disclosure, even in the absence of an active physician-patient relationship. The requirement of candid and complete disclosure will affect the counseling approach in testing for deleterious genes and in providing medical treatment for minors with hereditary diseases. Finding a duty to recall may impose further professional burdens on the geneticist to reach beyond the immediate counseling arena and to recontact patients, perhaps years after their initial visit to genetics clinic. PMID- 1867290 TI - Molecular detection of constitutional deletions in patients with retinoblastoma. AB - The recent cloning of the retinoblastoma (RB) gene as well as the identification of intragenic polymorphisms afford the necessary tools for the analysis of rearrangements using molecular hybridization. We searched for constitutional deletions by Southern blotting in 67 independent patients with normal karyotype comprising 15 familial and 52 sporadic cases. Among the latter, 33 were bilaterally and 19 unilaterally affected. We detected 6 deletions using cDNA probes covering almost all of the RB gene, as well as a genomic probe of the 5' part of the gene. With this approach, the incidence of detectable deletions was around 10%. No hot spots for deletion breakpoints were found. Asymptomatic carriers were detected in 2 families. The effectiveness of genetic counselling was largely improved by this approach. PMID- 1867291 TI - Familial translocation 5;14 resulting in an unbalanced offspring. AB - We report on an infant with multiple congenital anomalies possessing a derivative 14 chromosome in excess of the normal complement, resulting from transmission of a familial t(5;14)(p13;q22). The proposita's phenotypically normal mother, mentally retarded half-brother, and fetal sib are carriers of the apparently balanced translocation. Previous cases of similar familial t(5;14) are reviewed. The proposita's phenotype is characterized by failure to thrive, developmental retardation, cleft palate, congenital heart anomaly, abnormal hands and feet, unusual face with abnormal ears, and recurrent respiratory infections. The proposita died at age 9 months and postmortem examination showed multiple central nervous system, cardiopulmonary, gastrointestinal, and genital malformations. Our proposita's phenotype is attributable to contributions from both chromosomes and is consistent with the consequences of both the dup(5p) and dup(14q). PMID- 1867292 TI - The Noonan-CFC controversy. AB - The Noonan syndrome and the cardio-faciocutaneous (CFC) syndrome have been described as phenotypically and genetically distinct entities. However, the resemblance between them led some authors to question the validity of this separation. We review available clinical evidence to support the opposite view, namely, that the Noonan and CFC syndromes are indeed distinct and separate conditions, both falling within the broad and causally heterogeneous spectrum of the Noonan/congenital lymphedema phenotype. PMID- 1867293 TI - Journal policies concerning free access to scientific materials. PMID- 1867295 TI - Pituitary-gonadal axis in prepubertal boys with the fragile X syndrome. PMID- 1867294 TI - Type II collagen and noncollagenous protein screening in the human chondrodysplasias. PMID- 1867296 TI - Antibody indications of secondary and superimposed retinal hypersensitivity in retinitis pigmentosa. AB - Antibody reactions with recognized retinopathy-inducing retinal antigens may be interpreted to reflect ongoing autoimmune events responsible for some forms of vision loss. We sought evidence of secondary and superimposed retinal hypersensitivity indicated by such antibody reactivity in a random group of patients with retinitis pigmentosa. We identified patterns of immunologic reactivity within members of a group of 52 patients with retinitis pigmentosa, which suggests some patients with retinitis pigmentosa may experience consequential superimposed retinal hypersensitivity. Identifying subgroups of patients with retinitis pigmentosa who exhibit indications of retinal hypersensitivity to known uveitopathogenic retinal proteins may permit the reduction of their rate of retinal degradation by immunomodulation. PMID- 1867297 TI - Randomized, double-masked study of cyclosporine compared to prednisolone in the treatment of endogenous uveitis. AB - Fifty-six patients with bilateral sight-threatening noninfectious intermediate or posterior uveitis participated in a randomized double-masked study of the use of cyclosporine vs prednisolone in their treatment. Applying the end-point definitions, visual acuity or vitreal haze improved in only 13 of 28 (46%) patients in each group. The macular edema resolved in seven of 15 patients of the cyclosporine-treated group, and in ten of 16 patients of the prednisolone-treated group (P = .376). Patients whose therapies failed both cyclosporine and prednisolone trials were treated with both drugs, which resulted in additional patient improvements. Secondary effects were observed in both therapeutic alternatives, the most notable being alterations in serum creatinine concentration and hypertension with the dosage of cyclosporine used. PMID- 1867298 TI - Clinical patterns and associated conditions in chronic uveitis. AB - We determined the relative frequencies of the different types of chronic uveitis, and the possible associated conditions, among 400 consecutive patients with chronic uveitis examined during the years 1982 through 1988. Of the 400 patients, 183 (45.75%) had anterior uveitis, 98 (24.5%) ahd panuveitis, 61 (15.3%) had intermediate uveitis, and 58 (14.5%) had isolated posterior uveitis. Only four of the 98 patients with panuveitis (4.1%) were considered idiopathic after a comprehensive examination, whereas 94 of the 183 patients with anterior uveitis (51.4%) were similarly classified. We found an associated condition in 242 of the 400 patients of the study group (60.5%). Of these 242 patients, 61 had Behcet's disease, which constituted the most frequently encountered associated condition in this study. Of the 61 patients with Behcet's disease, 58 had panuveitis and constituted 59.2% of the panuveitis group. Of the 61 patients with intermediate uveitis, 17 (27.9%) had a concurrent disease. An associated condition was found in 95% and 96.2% of patients with unilateral and bilateral panuveitis, respectively, but in none of the patients with unilateral intermediate uveitis. Environmental, cultural, or genetic factors may be accountable for the differences discovered between our findings and those of previously published studies from the United States and England with respect to relative frequencies of some of the associated diseases in patients with chronic uveitis. PMID- 1867299 TI - An updated classification of retinal detachment with proliferative vitreoretinopathy. AB - The Retinal Society classification on proliferative vitreoretinopathy of 1983 has been updated to accommodate major progress in understanding of this disease. There are three grades describing increasing severity of the disease. Posterior and anterior location of the proliferations have been emphasized. A more detailed description of posterior and anterior contractions has been made possible by adding contraction types such as focal, diffuse, subretinal, circumferential contraction, and anterior displacement. The extent of the abnormality has been detailed by using clock hours instead of quadrants. PMID- 1867300 TI - Disk drusen and angioid streaks in pseudoxanthoma elasticum. AB - Visual field loss secondary to optic disk drusen became evident before the development of angioid streaks in a patient with pseudoxanthoma elasticum. The incidence of optic disk drusen in cases of pseudoxanthoma elasticum is 20 to 50 times greater than that in the healthy population. We postulate that the abnormal aggregation of macromolecules with a high affinity for calcium (resulting in abnormalities in elastin in cases of pseudoxanthoma elasticum) also develops at the cribriform plate, disrupting axonal flow and leading to disk drusen formation. Pseudoxanthoma elasticum is associated with marked cardiovascular and gastrointestinal morbidity. Moreover, macular hemorrhage and precipitation of angioid streaks have frequently been noted after trauma. Prompt diagnosis of pseudoxanthoma elasticum will allow necessary prophylaxis and must be considered in patients with optic disk drusen. PMID- 1867301 TI - Regional and long-term variability of fundus measurements made with computer image analysis. AB - We studied the variability of optic disk and peripapillary nerve fiber layer surface contour measurements made by use of computer-image analysis. Six hundred twenty-five measurements of surface contour were made on each eye by use of simultaneous stereoscopic videography. Regional differences in short-term measurement variability were studied in 12 eyes (six normal and six glaucomatous), each imaged nine times over several days. The widths of the 95% confidence interval for the measurements averaged 82 microns for the juxta papillary surface and 132 microns for the disk surface. Measurements of peripapillary surface contour were significantly less variable than were measurements of the disk surface (P = .000). The greatest variability was detected along large blood vessels and at steep contours. Long-term variability was studied in a separate group of 30 clinically stable patients with glaucoma, each imaged three to six times over a period of more than one year. The widths of the 95% confidence intervals were 132 microns for the peripapillary surface and 217 microns for the disk surface. The long-term variability was significantly greater than the short-term variability (P = .000). The peripapillary nerve fiber layer surface, located away from the margins of large vessels, may provide the most dependable measurements of contour. These estimates of long-term variability of optic disk and peripapillary contour measurements provide clinically relevant confidence intervals with which to detect progressive glaucomatous nerve fiber damage. PMID- 1867302 TI - Treatment of pseudotumor cerebri by primary and secondary optic nerve sheath decompression. AB - We performed optic nerve sheath decompression in 53 patients (101 eyes) with pseudotumor cerebri and visual loss. Sixty-nine eyes (85 patients) with acute papilledema uniformly had improved visual function after optic nerve sheath decompression. Of 32 eyes with chronic papilledema (18 patients), only ten had improved visual function after optic nerve sheath decompression. This difference was significant (P = .0001). Thirteen eyes required secondary or tertiary optic nerve sheath decompression after an initial successful result. Eleven of 13 eyes had improved visual function after repeat optic nerve sheath decompression. We believe that patients with acute papilledema and visual loss should be offered optic nerve sheath decompression, and if symptoms recur, repeat optic nerve sheath decompression is a safe and effective treatment option. PMID- 1867303 TI - The effect of topical administration of indomethacin on symptoms in corneal scars and edema. AB - We conducted a masked randomized study of 50 patients to evaluate the effect of administration of topical indomethacin 1% suspension on symptoms in corneal scars, edema, infiltrates, and erosions. Patients with symptoms (photophobia, pain, itching, burning sensation, foreign-body sensation, and tearing) were treated with topically administered indomethacin 1% or placebo and monitored for eight weeks. The severity of the complaints was rated and the scores were evaluated (Wilcoxon rank-sum test). Of the 25 patients treated with indomethacin, 21 (84%) had improvement in symptoms and the severity of each of the symptoms was significantly decreased. Of the 25 patients treated with placebo, one (4%) had improvement in symptoms without statistical change of the severity of the symptoms. However, when the placebo-treated patients received indomethacin drops, the symptoms were significantly decreased (P less than .002). This study suggests that topical administration of indomethacin 1% may reduce ocular symptoms in patients with corneal scars, edema, or erosions. PMID- 1867304 TI - Fitting of aspheric high gas-permeable rigid contact lenses to scarred corneas. AB - Scarring of the cornea often results in an irregular corneal surface, which causes scattering in light perception. Therefore, the impaired visual acuity cannot be adequately corrected by spectacles in most cases. In this study, high oxygen-transmissible aspheric rigid lenses were fitted, with computer assistance, in 26 scarred eyes of 23 consecutive patients. In 15 of 26 eyes (57.7%), a successful fitting with good vision, no complications, and a sufficiently long wearing time was accomplished. The main lens-related complications included fluorescein-staining epithelial defects in five of 26 eyes (19.2%) and epithelial edema in two of 26 eyes (7.7%). Computer-aided fitting was of limited value because keratometer readings were not measurable in 50% of the cases. The results of this study indicate that the application of high oxygen-transmissible aspheric rigid contact lenses may obviate corneal surgery. PMID- 1867305 TI - The effect of light intensity and dose of dilute pilocarpine eyedrops on pupillary constriction in healthy subjects. AB - The aim of this study was to investigate variables that influence the degree of pupillary constriction to dilute pilocarpine eyedrops in healthy control subjects. The pupillary response to 50 microliter of pilocarpine 0.0625% in darkness, dim light, and bright light was measured photographically in 15 healthy adults. Constriction to pilocarpine was greater in darkness and in dim light than in bright light, indicating that the pupillary-light reflex masked the constrictive effect of pilocarpine. In ten other subjects pupillary constriction to 50 microliters of pilocarpine 0.04%, and to 50 and 100 microliters of pilocarpine 0.0625%, was measured on separate occasions. Pupillary constriction increased in proportion to the volume and concentration of pilocarpine. Data for pupillary constriction to 50 microliters of pilocarpine 0.0625% in dim light were determined in all 25 subjects. PMID- 1867306 TI - Concomitant lymphangioma and arteriovenous malformation of the orbit. AB - An 8-year-old girl had an orbital-adnexal lymphangioma and ipsilateral orbital and middle cranial fossa arteriovenous malformations. High-resolution magnetic resonance image scanning, orbital ultrasonography, and digital subtraction angiography were used for diagnosis and preoperative assessment. Complications related to this vascular neoplasm included amblyopia, acute hemorrhage with proptosis, exposure keratitis, cosmetic deformity, and recurrent preseptal cellulitis. The girl was treated with both embolization and orbital surgery for recurrent hemorrhage and proptosis. We postulated that the coexistence of a lymphangioma and arteriovenous malformation represents an unusual and extensive maldevelopment of vascular embryogenesis. PMID- 1867307 TI - Human immunodeficiency virus, herpes zoster, and the retina. PMID- 1867308 TI - Penicillin: 1929-1991. PMID- 1867309 TI - Inferior rectus muscle palsy after retrobulbar anesthesia for cataract surgery. PMID- 1867310 TI - Measurement of the radius of corneal curvature with the Maloney surgical keratometer. PMID- 1867311 TI - A comparison of the size of the burn produced by Rodenstock and Goldmann contact lenses. PMID- 1867312 TI - Bone erosion in nasolacrimal duct obstruction. PMID- 1867313 TI - Stiles-Crawford effect and color matching in Stargardt's disease. PMID- 1867314 TI - A physical analysis of the factors that determine the contour of the iris. PMID- 1867315 TI - Delayed-onset pseudophakic endophthalmitis. PMID- 1867316 TI - Analysis of TNF alpha-induced DNA strand breaks at the single cell level. AB - Treatment of L929 cells with TNF alpha initiates apoptosis and subsequent cell death. The authors have visualized sites of DNA damage in situ by using DNA polymerase to synthesize new strands from the DNA strands breaks as starting point. Biotin-dUTP was incorporated into the newly synthesized strand and visualized by immunocytochemistry. DNA strand breaks were first observed 3 to 4 hours after contact with TNF alpha and preceded cell death. Limiting doses of TNF alpha caused DNA strand breaks only in a subpopulation of L929 cells. At a low dose, TNF alpha led to DNA damage without any subsequent loss of cell viability. The new assay also detects DNase-induced single strand breaks and thus is able to visualize apoptotic as well as non-apoptotic types of DNA damage. PMID- 1867317 TI - Increased macrophage colony-stimulating factor in neonatal and adult autoimmune MRL-lpr mice. AB - Abnormal macrophages in MRL-lpr mice are implicated in the pathogenesis of autoimmune disease. These mice die of lupus nephritis by 5 to 6 months of age. This study reports that MRL-lpr mice have an increased level of circulating macrophage colony-stimulating factor (M-CSF) detectable as early as 1 week of age. Macrophage colony-stimulating factor decreased between 2 and 4 months and then steadily increased beginning at 4 months of age. In contrast, M-CSF was not detected in sera from congenic MRL-++ mice, normal C3H/FeJ mice, two other mouse strains with the lpr gene (B6-lpr and C3H-lpr), or another lupus model, the NZB/W mouse. These observations indicate that the lpr gene alone is not responsible for inducing this growth factor, and elevated M-CSF is not required for all forms of murine lupus. The entire source of serum M-CSF is not clear. The unique T cells regulated by the lpr gene are not responsible for the increased serum M-CSF levels, as no M-CSFs could be detected in supernatants from cultured lymph nodes from MRL-lpr mice, and the steady-state levels of M-CSF mRNA in lymph nodes and spleens in MRL-lpr, C3H-lpr mice and in their respective congenic strains were similar. The steady-state M-CSF mRNA transcripts in liver, lung, and bone marrow in MRL-lpr, MRL-++, and C3H/FeJ mice were also similar. Macrophage colony stimulating factor transcripts were clearly elevated in the kidneys of MRL-lpr mice, suggesting a renal source of circulating M-CSF. The increase of M-CSF might be responsible for the increased numbers and enhanced functions of macrophages, which in turn cause tissue destruction in MRL-lpr mice. PMID- 1867318 TI - Kinetics of Borrelia burgdorferi dissemination and evolution of disease after intradermal inoculation of mice. AB - Borrelia burgdorferi dissemination to selected target organs was examined on days 1, 2, 3, 4, 7, 10, 15, 21, and 30 after intradermal inoculation of 4-week-old C3H mice. Infection was determined by culture (blood, spleen, kidney, ear punch); polymerase chain reaction (PCR) for outer surface protein A (OSP A) DNA (ear punch); histology and spirochete histochemistry (spleen, kidney, skin, heart, joints); and OSP A DNA in situ hybridization (joints, heart). Blood or spleen of most mice were culture positive by day 3 and ear punch by day 10. Polymerase chain reaction performed on ear punches was also positive by day 10. Inflammation of joints and tendons began on days 4 through 7 and heart on days 7 through 10, which coincided with colonization of tissues with spirochetes. Spirochetes were multifocal in distribution, with a predilection for collagenous connective tissue of joints, heart, arteries, nerves, muscle, skin, and other tissues. Relative numbers of spirochetes peaked at 15 days, then decreased by 21 days. Gamma M immunoglobulin (IgM) antibody was detectable on immunoblots as early as day 4, with subsequent declining reactivity, and IgG antibody was detectable by day 7, with expanding reactivity to multiple antigens through day 30. PMID- 1867319 TI - Immunohistochemical analysis of neural cell adhesion molecules. Differential expression in small round cell tumors of childhood and adolescence. AB - The neural cell adhesion molecule (NCAM) was discovered in a search for cell surface antigens of chicken neurons that contribute to cell adhesion and pattern formation during development. Homologous adhesion molecules have been identified in several species, including humans. In this immunohistochemical study, the authors examine the role of human NCAM in tumor diagnosis. The authors used a monoclonal antibody (MAb), 5.1H11, to examine NCAM immunoreactivity in frozen sections of more than 450 tumors, including more than 80 small round cell tumors (SRCT) of childhood and adolescence (neuroblastomas, Ewing's sarcomas [ES], peripheral neuroepitheliomas [PN], primitive neuroectodermal tumors [PNET], esthesioneuroblastomas, malignant ectomesenchymoma, medulloblastomas, small cell osteosarcomas, mesenchymal chondrosarcomas, embryonal rhabdomyosarcomas, and lymphomas). The authors show that 1) neuroblastomas and primary brain tumors are NCAM+; 2) ES, most PN/PNETs, and melanomas are NCAM-; 3) embryonal rhabdomyosarcomas and various other sarcomas are NCAM+; 4) neuroendocrine tumors are NCAM+; 5) subsets of carcinomas of kidney, ovary, lung and other organs are NCAM+; and 6) lymphoid tumors are NCAM-. Tests with normal fetal and adult tissues indicate that these findings reflect only in part the NCAM phenotypes of corresponding normal tissues. Notably the NCAM- phenotype of ES and PN/PNET is not explained by current histogenetic models for these tumors, which suggest a primitive neuroectodermal origin. Finally the authors show that NCAM expression among SRCT has an inverse relationship with the expression of p30/32MIC2, a cell surface antigen of ES and PN/PNET detected with MAb HBA71. These results suggest that immunohistochemical assays for NCAM and p30/32MIC2 expression may aid in the further characterization of SRCT of childhood and adolescence. PMID- 1867320 TI - Immunohistochemical analysis of Ewing's sarcoma cell surface antigen p30/32MIC2. AB - Monoclonal antibody (MAb) HBA71, which was raised against Ewing's sarcoma cells, recognizes a cell-surface glycoprotein, p30/32MIC2, that is encoded by the MIC2 gene in the pseudoautosomal region of human chromosomes X and Y. This immunohistochemical study evaluates the specificity and sensitivity of MAb HBA71 for tumor diagnosis. Frozen and paraffin-embedded tissues of more than 300 tumors of diverse histologic type, including more than 100 small round cell tumors of childhood and adolescence, were tested with this MAb by the avidin-biotin immunoperoxidase procedure. The authors found HBA71 immunoreactivity in 61 of 63 Ewing's sarcomas studied and 9 of 11 primitive neuroectodermal tumors and peripheral neuroepitheliomas. HBA71-negative tumors included neuroblastomas (0 of 24), melanomas (0 of 13), an esthesioneuroblastoma, small cell osteosarcomas (0 of 2), a malignant ectomesenchymoma, desmoplastic SRCT (0 of 5), and medulloblastomas (0 of 5). Heterogeneous expression of HBA71 immunostaining was found in some embryonal rhabdomyosarcomas (3 of 14) and astrocytomas (4 of 7), and in a few neuroendocrine tumors (4 of 26), carcinomas (3 of 94), and lymphomas (6 of 30). Because Ewing's sarcomas are consistently HBA71 positive, the authors searched for antigen-positive normal cells that may represent precursors for these tumors; however, no obvious candidate for the elusive cell of origin for Ewing's sarcoma was identified in the normal fetal tissues tested. Their findings indicate that HBA71 is a highly restricted cell-surface antigen of Ewing's sarcomas and primitive neuroectodermal tumors, and immunohistochemistry employing this antibody may be of value in the differential diagnosis of selected small round cell tumors in childhood and adolescence. PMID- 1867321 TI - Tumor necrosis factor alpha mRNA and protein are present in human placental and uterine cells at early and late stages of gestation. AB - Tumor necrosis factor alpha (TNF-alpha), a polypeptide that regulates cellular growth and modulates the synthesis of various cell surface and secreted molecules, has been identified in the pregnant uterus. To determine which specific cells transcribed and translated this gene, extraembryonic fetal tissues (placenta and membranes) and uterine tissue from early and late stages of gestation were analyzed for TNF-alpha mRNA by in situ hybridization using biotinylated antisense and sense TNF-alpha probes, and for immunoreactive TNF alpha using two monoclonal antibodies. Tumor necrosis factor-alpha transcripts and protein were identified in both extraembryonic and maternal cells. In first trimester placental villi, TNF-alpha mRNA was present in syncytiotrophoblast but was low to absent in cytotrophoblast and villous stromal cells. Decidual and epithelial cells in maternal tissues contained TNF-alpha transcripts. In term placentas, both syncytiotrophoblast and villous stromal cells contained TNF-alpha mRNA, and transcripts were present in maternal cells in the decidua adjacent to the extraplacental membranes. In both first-trimester and term tissues, coincident expression of TNF-alpha mRNA and immunoreactive TNF-alpha was demonstrated. The results of this study show that TNF-alpha is synthesized by cells in both extraembryonic membranes and maternal tissues during human gestation and that transcription in specific types of cells is influenced by gestational age. These observations are consistent with a major role for TNF alpha in the dynamic developmental events of human pregnancy. PMID- 1867323 TI - Mesangial cell activation by bacterial endotoxin. Induction of rapid cytoskeletal reorganization and gene expression. AB - Cultured glomerular mesangial cells (MC) respond to low concentrations of bacterial endotoxin (ET) by secreting prostaglandins and interleukin-1. To evaluate further the nature of ET-induced mesangial cell activation, the authors evaluated the effects of this agent on MC morphology and cytoskeletal organization. Bacterial ET, in concentrations as low as I ng/ml, induced reversible membrane ruffling, cellular rounding, and extension of many filopodia and lamellopodia. Augmented fluid-phase pinocytosis occurred in parallel, as determined by transmission electron microscopy and tritiated sucrose uptake. These cellular morphologic and functional changes were associated with an extensive, but reversible, depolymerization of actin microfilaments. Actin gene expression was also modified by ET. At 4 to 6 hours after ET exposure, Northern blot analysis showed a twofold to fourfold increase in actin mRNA levels. In situ hybridizations of ET-stimulated cells at the light and electron microscopic levels demonstrated a markedly asymmetric distribution of actin mRNA, which was localized in the cellular periphery at filopodial and lamellopodial extensions, presumably sites of new actin protein synthesis. It is concluded that ET effects on MC are distinct from the nonspecific lytic or 'toxic' actions described for other cell types. Endotoxin induces a global activation of this cell type associated with major changes in membrane structure, cytoskeletal organization, and gene expression, which resemble in many respects the responses to peptide mitogens. PMID- 1867322 TI - Abnormal expression of histocompatibility and mitochondrial antigens by cardiac tissue from patients with myocarditis and dilated cardiomyopathy. AB - Autoantibodies against the adenine nucleotide translocator (ANT), the branched chain alpha-ketoacid dehydrogenase (BCKD) complex proteins, and myosin have been implicated in the pathogenesis of human dilated cardiomyopathy (DCM). Cardiac tissue from patients with DCM and, for control purposes, cardiac tissue from patients with other forms of cardiomyopathy and from patients with no history of cardiac disease were stained with heterologous and ANT-, BCKD-, and myosin specific affinity-purified sera from DCM patients. Data demonstrate that although anti-myosin stains tissues from both patients and normal controls, the ANT- and BCKD-specific heterologous and affinity-purified sera from DCM patients stain only cardiac tissues from DCM patients. Intense staining in patchy areas of cardiac tissue suggests that abnormal increased expression of these putative autoantigens occurs in discrete areas of cardiac myocytes. The reactivity of the antisera was organ specific and only seen in tissues from DCM patients. The organ and disease specificity of these findings suggests that such expression may play an important role in the pathogenesis of human DCM. PMID- 1867324 TI - Pigeon monocyte/macrophage lysosomes during beta VLDL uptake. Induction of acid phosphatase activity. A model for complex arterial lysosomes. AB - Lysosomes have long been implicated as a factor contributing to the progression and complication of atherosclerosis. The authors' laboratory previously has shown that lysosomal ultrastructure in arterial macrophage foam cells is altered as primary lysosomes give rise to large pleiomorphic organelles on lipid accumulation during lesion progression. To further explore the subcellular alterations in lysosomes and associated organelles during foam cell formation, three-dimensional (3D) intermediate voltage electron microscopy was used to examine monocyte-derived macrophages (monocyte/macrophages) during early in vitro uptake of beta migrating very-low-density lipoproteins (beta VLDL). Lysosomes were identified using acid phosphatase cytochemistry, and in control cells these organelles constituted 3.5% of the total cytoplasmic volume. Both primary and secondary lysosomes were observed. Upon beta VLDL uptake, the total volume of acid-phosphatase-positive organelles increased threefold over 30 minutes, and the reaction product was found in three additional morphologically distinct structures: tubular lysosomes, membrane stacks, and endoplasmic reticulum with widened cisternae. The proportion of the cell occupied by each of the five acid phosphatase-positive organelles was quantitated at 10 minutes, 30 minutes, 1 hour, and 4 hours of beta VLDL incubation, and their relative abundance was compared with controls that were processed either with no lipoprotein challenge or albumin incubation for 1 hour. Secondary lysosomes compartment volume peaked at 30 minutes; over the ensuing 3.5 hours, however, the reaction progressively shifted to three new membrane-limited locations. Our observations document the complex 3D organization and spacial relationships among the acid-phosphatase positive structures induced by lipoprotein uptake. The 3D organization patterns for acid-phosphatase-positive lysosomes in lipoprotein-stimulated pigeon monocyte/macrophages were similar in several aspects to the complex lysosomes previously observed in the macrophages of pigeon arterial lesions. PMID- 1867326 TI - Cell migration and actin organization in cultured human primary, recurrent cutaneous and metastatic melanoma. Time-lapse and image analysis. AB - Random cell migration and actin organization in seven human primary, recurrent cutaneous, and metastatic melanoma cell lines were studied by time-lapse video recording and image analysis. The migration of over 800 randomly selected cells from the cell lines were recorded using an inverted microscope with an attached incubator housing. The fraction of cells with random migration rates greater than 10 microns/hour was 8% in an established primary melanoma cell line, 2% and 34% in two recurrent cutaneous melanoma cell lines, and 5%, 30%, 31%, and 60% in four metastatic cell lines. The three metastatic cell lines with significantly higher mean migration rates (P less than 0.001) were derived from lymph node metastases, whereas the fourth metastatic cell line was derived from a visceral metastasis. The cellular morphology and presence of cell nests in the original tissue correlated with in vitro cell morphology and the formation of colonies. The ability of cells to organize actin into stress fibers directly correlated with significantly higher random migration rates and lack of colony formation. Characterization of random migration rates and actin organization of human melanoma cells that are isolated from different stages of tumor progression may lend insight into metastasis. PMID- 1867325 TI - Freshly isolated and cultured human monocytes obtained by plasmapheresis kill schistosomula of Schistosoma mansoni. AB - The efficacy of human peripheral blood monocytes (PBM) in killing of schistosomula is controversial. The purpose of this study was to determine the schistosomulacidal activity of human monocytes isolated by two different techniques. Peripheral blood monocytes were obtained either by venipuncture (PBMv) or plasmapheresis (PBMp), purified on Ficoll-Paque, and cultured briefly. The cells then were incubated with schistosomula (cell parasite ratio of 10(4):1) for 16 to 18 hours with or without interferon-gamma IFN-gamma (600 U/ml) or sera from patients with schistosomiasis as a source of antischistosomal antibodies (HASA). Freshly isolated PBMv treated with IFN-gamma or HASA did not kill schistosomula. Freshly isolated PBMp alone killed 22 +/- 13% (mean +/- standard deviation [SD]; n = 9) of worms over background and after incubation with IFN gamma and HASA, 30 +/- 17%. PBMp cultured in vitro for 7 days killed 50 +/- 15% (mean +/- SD; n = 12) of the schistosomula. Pretreatment of the cells with IFN gamma and incubation with HASA did not significantly enhance the parasite killing beyond this level. Electron microscopy showed that freshly isolated PBMp attached to the worms and fused occasionally with the outer tegumental membrane. Granules constituted 1.4% of the cytoplasmic volume. Degranulation onto the parasite surface was not observed. Peripheral blood monocytes obtained by plasmapheresis accumulated glycogen during in vitro culture with the parasite and released threefold more H2O2 than PBMv after exposure to phorbol myristate acetate. Thus plasmapheresis increases the schistosomulacidal activity of PBM, enhances the generation of H2O2 and promotes the accumulation of glycogen. PMID- 1867328 TI - Distribution patterns of type VII collagen in normal and malignant human tissues. AB - The distribution of basement membrane type VII collagen was detected immunohistochemically and compared in normal human organs and their neoplastic derivatives using monoclonal antibody LH7.2. In normal tissues, type VII collagen was found to be restricted to the basement membrane surrounding or underlying combined epithelia, such as those lining breast, prostate, and bronchus, which are composed of a basal and luminal cell layer, and stratified epithelia, such as larynx, esophagus, trachea, vagina, ectocervix, and epidermis. No type VII collagen was found in the "simple' epithelia lining the major part of the gastrointestinal tract (GI) tract, such as liver, stomach, and intestine, or around blood vessels, muscle, and nerve fibers, which are surrounded, however, by a basement membrane containing type IV collagen and laminin. When tested in benign and malignant local tumors, antibody LH7.2 showed staining patterns partly similar to those observed in the corresponding normal tissues. This resulted in a well-circumscribed positive reaction around ducts in carcinomas in situ of the breast, in benign prostate tumors, in pleomorphic adenomas, and in a negative reaction in tumors of the GI tract. Furthermore type VII collagen was predominantly seen in carcinomas with a squamous differentiation, such as squamous carcinomas of the lung, head and neck, vulva, and vagina. These results indicate that the presence of type VII collagen in malignant tumors is correlated with (squamous) differentiation rather than with the origin of the tumor. With tumor progression, an increased presence of type VII collagen, as compared with normal urinary bladder, was found in infiltrating transitional cell carcinomas. Thus, although in general invasive and metastatic tumors do not express extensively type VII collagen, exceptions to this rule exist in bladder cancer, squamous carcinomas of the lung, tumors of the head and neck region, female genital tract tumors, and in some adenocarcinomas of the breast. PMID- 1867327 TI - Increased steady-state levels of mRNA coding for extracellular matrix components in kidneys of NZB/W F1 mice. AB - The present study was carried out to determine how mRNA levels of extracellular matrix (ECM) components including alpha 1(IV) chain, laminin A, B1 and B2 chains, heparan sulfate proteoglycan (HSPG), alpha 1(I) chain, and alpha 1(III) chain are regulated in the kidney of NZB/W F1 mice. Messenger RNA levels for ECM genes except for laminin A chain increased significantly with the progression of nephritis in NZB/W F1 mice. In the NZW kidneys, however, the mRNA levels for alpha 1(IV) chain, laminin B1 and B2 chains, and HSPG declined markedly with age, whereas those for alpha 1(I) and alpha 1(III) chains showed little difference throughout the experimental period. Messenger RNA levels of beta-actin remained constant, and those of laminin A chain could not be detected in either control or diseased kidneys. Immunofluorescent microscopy showed that the intensity and distribution of staining of collagen IV, laminin, and HSPG in the glomeruli of NZB/W F1 mice increased markedly with the progression of disease. Types I and III collagen were not detected in the glomeruli of NZB/W F1 mice by immunofluorescence until 24 weeks of age, after which increased amounts of these collagens were found in the glomeruli and interstitium with progression of disease. These results suggest that increased levels of mRNA coding for ECM components and increased accumulation of these proteins may contribute to a cascade of events, leading to chronic renal injury in lupus nephritis. PMID- 1867329 TI - Tibial meniscal dynamics using three-dimensional reconstruction of magnetic resonance images. AB - The human knee joint represents a complex biomechanical system of which the menisci are an integral component. At present, little data exists describing the meniscal kinematics of the intact knee. Accordingly, a three-dimensional reconstruction magnetic resonance image model was used to explore this issue. Five fresh cadaveric knees were examined by magnetic resonance imaging throughout a full range of motion at 10 degrees intervals. Computer three-dimensional images of the menisci were generated and evaluated for anteroposterior excursion and deformation. During flexion, the posterior excursion of the medial meniscus was 5.1 mm, while that of the lateral meniscus was 11.2 mm. The anterior horn segments were shown to be more mobile than the posterior horn segments bilaterally. Prior limitations of meniscal kinematic assessment may be overcome with advanced imaging techniques such as magnetic resonance imaging and three dimensional reconstruction. The menisci are highly mobile and easily deformed structures within the intact, cadaveric knee. This imaging technique may prove useful in the elucidation of meniscal dynamics. In the future, similar techniques may be applied clinically to aid in the diagnosis of joint dysfunction. PMID- 1867330 TI - Tensile properties of the human femur-anterior cruciate ligament-tibia complex. The effects of specimen age and orientation. AB - The structural properties of 27 pairs of human cadaver knees were evaluated. Specimens were equally divided into three groups of nine pairs each based on age: younger (22 to 35 years), middle (40 to 50 years), and older (60 to 97 years). Anterior-posterior displacement tests with the intact knee at 30 degrees and 90 degrees of flexion revealed a significant effect of knee flexion angle, but not of specimen age. Tensile tests of the femur-ACL-tibia complex were performed at 30 degrees of knee flexion with the ACL aligned vertically along the direction of applied tensile load. One knee from each pair was oriented anatomically (anatomical orientation), and the contralateral knee was oriented with the tibia aligned vertically (tibial orientation). Structural properties of the femur-ACL tibia complex, as represented by the linear stiffness, ultimate load, and energy absorbed, were found to decrease significantly with specimen age and were also found to have higher values in specimens tested in the anatomical orientation. In the younger specimens, linear stiffness (242 +/- 28 N/mm) and ultimate load (2160 +/- 157 N) values found when the femur-ACL-tibia complex was tested in the anatomical orientation were higher than those reported previously in the literature. These values provide new baseline data for the design and selection of grafts for ACL replacement in an attempt to reproduce normal knee kinematics. PMID- 1867331 TI - The current state of functional knee bracing research. A review of the literature. AB - This paper reviews recent research on functional knee bracing. Research is categorized by subject, approach, or technique. The authors conclude that, while there is a good deal of excellent research available, there is little data to assist the clinician in selecting an orthosis for a specific application. The authors recommend that future investigations address the physiologic aspects of functional knee bracing and that brace manufacturers assume more responsibility in the validation of both existing and future brace designs. PMID- 1867332 TI - Acute Grade III ulnar collateral ligament ruptures. A new surgical and rehabilitation protocol. AB - A review is presented here of 36 cases, seen since 1980, of acute Grade III (unstable) sports-related sprains of the thumb metacarpophalangeal joint. In all cases, the injury involved the ulnar collateral ligament. A Stener lesion was present in 97% of cases. Followup was from 2.0 to 8.5 years, the average being 3.9 years. All of the patients underwent repeat examination and radiography at followup. The first seven patients were treated by "traditional" pull-out suture and K-wire fixation, put into a cast for 4 weeks, and then gradually mobilized over 4 additional weeks. Thereafter, a "new method" was used. Avulsed ulnar collateral ligament stumps were sutured to the tendinous insertion of the adductor pollicis or to a soft tissue remnant using strong suture material. Large bony avulsions were pinned; small fragments were excised and the ligament was repaired. This latter method of repair was quite strong and allowed rapid mobilization: only 2 weeks in a cast, then a hand-mounted thumb spica orthosis was used while therapy progressed. Of the patients treated with the new method, 84% had excellent results and, overall, were able to return to sports sooner than patients treated with the traditional method. Pain, stability, and strength were corrected equally between groups; however, strength was restored more rapidly in the new method group. Range of motion was reduced equally in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867333 TI - The long-term followup of primary anterior cruciate ligament repair. Defining a rationale for augmentation. AB - Fifty primary ACL repairs using the Marshall multiple suture technique were analyzed. The average age at surgery was 23 years (range, 15 to 56), with 76% under the age of 30. The average followup was 61.3 months (range, 48 to 86). The average time from injury to surgery was 7 days (range, 1 to 18). Eighty percent of the injuries were sports-related with football and skiing predominating. Thirty-eight percent were "isolated" ACL tears, and 62% had associated injuries. There was a 46% incidence of meniscal tear with 59% of the meniscal tears being repaired. The postoperative evaluation included a multifactorial analysis correlating 43 variables including subjective, objective, radiographic, and KT 1000 data. The Hospital for Special Surgery Knee Diagnostic Score, a clinical objective score based on the postoperative Lachman and pivot shift examination, a KT-1000 arthrometer data score, and an overall combined assessment score were determined. The results showed 59% excellent, 18% good, 14% fair, and 8% poor. The Lachman test was diagnostic in all cases. The quality of ACL tissue at repair was rated excellent or good in 62% of the cases. Four patterns of ACL tears were distinguished by the location of the tear. Football injury, younger age, increased peroperative pivot shift, midsubstance Type IV tear, and return of full motion correlated with poor postoperative results. Increasing age, tight jointedness, Type I tears, and a 5 degrees flexion contracture correlated with good postoperative results. PMID- 1867334 TI - Electromyographic analysis of the glenohumeral muscles during a baseball rehabilitation program. AB - Many exercises are used to strengthen the glenohumeral muscles, but there have been limited studies to evaluate the exercises. Thus, the purpose of this study was to decide how the muscles responsible for humeral motion can best be exercised in a rehabilitation program for the throwing athlete. Dynamic, fine wire, intramuscular electromyography was carried out in 15 normal male volunteers performing 17 shoulder exercises derived from a shoulder rehabilitation program used by professional baseball clubs. The four rotator cuff muscles were studied, as well as other positioners of the humerus, including the pectoralis major, latissimus dorsi, and three portions of the deltoid. The electromyographic activity was synchronized with cinematography and averaged over 30 degrees arcs of motion. An exercise was considered to be a significant challenge for a muscle if it generated at least 50% of its predetermined maximum contraction over three consecutive arcs (i.e., a 90 degrees range). Four exercises were consistently found to be among the most challenging exercises for every muscle. These shoulder exercises consisted of 1) elevation in the scapular plane with thumbs down, 2) flexion, 3) horizontal abduction with arms externally rotated, and 4) press-up. This study documents that the minimum for an effective and succinct rehabilitation protocol for the glenohumeral muscles would include these exercises. PMID- 1867335 TI - A rationale for predicting anterior cruciate graft impingement by the intercondylar roof. A magnetic resonance imaging study. AB - This study was designed to analyze how anterior tibial tunnel placement can result in graft impingement by the intercondylar roof. The relationship of the ACL to the intercondylar roof was studied using magnetic resonance scans. An attempt was made to predict the amount of bone that may need to be removed from the intercondylar roof to prevent impingement on a 10 mm thick ACL graft. Magnetic resonance scans of 19 normal ACLs were analyzed. The amount of bone removal required to correct roof impingement was determined for a graft placed either eccentrically or centrally within the ACL insertion, and within the bulk of the normal ACL fibers. An eccentric tibial tunnel placement required approximately 5 to 6 mm and a central placement required 2 to 3 mm of bone removal from the intercondylar roof to prevent impingement. Placing the graft within the bulk of the ACL fibers, just 3 mm posterior to the center of the ACL insertion, required little bone resection to prevent impingement. To prevent ACL graft impingement, roofplasties need to be performed in both acute and chronic ACL reconstructions if the presently accepted locations for positioning the tibial tunnel are used. A more anteriorly placed tibial tunnel requires more bone removal to prevent roof impingement than a more posteriorly positioned tibial tunnel. PMID- 1867336 TI - Results of knee manipulations after anterior cruciate ligament reconstructions. AB - We analyzed the results of knee manipulations in 42 knees that had persistent flexion or extension deficits after intraarticular ACL reconstructions. All manipulations were done under a spinal or general anesthetic and, in 10 cases, arthroscopic debridement of adhesions also was performed. The average time from reconstruction to manipulation was 7 months (range, 3 to 14 months) and the average followup was 26 months (range, 6 to 56 months). At manipulation, average flexion was increased from 95 degrees to 136 degrees and average extension from 11 degrees to 3 degrees. In no case was motion gained at the expense of joint stability and, at final followup, average flexion and extension were 127 degrees and 4 degrees, respectively. The final range of motion achieved was not affected by the time to manipulation, severity of premanipulation flexion deficit, or concomitant arthroscopic debridement of adhesions. However, knees with premanipulation extension deficits of greater than or equal to 15 degrees achieved significantly less final extension than knees with lesser premanipulation deficits. Overall, manipulations were a safe and effective method for improving both flexion and extension in 86% of the knees that had restricted motion after ACL reconstructions. PMID- 1867337 TI - Biomechanics of the golf swing in players with pathologic conditions of the forearm, wrist, and hand. AB - Golf is an activity generally stressful to the hands and wrists and particularly can produce increasing symptoms in players with underlying problems such as hand and wrist arthritis or tendinitis. The purpose of this study was to quantitate wrist motion and club head/ball impact force in subjects with pathologic conditions of the hand, wrist, or forearm, within a laboratory environment. A regular straight-handled golf club was compared to a new BioCurve handle design that has a 19 degrees ulnar bend. We measured and compared the effect of the two grips on wrist motion, club head velocity, ball impact force, ball impact location, and isometric torsional strength in 20 subjects who had a variety of upper extremity disorders. This data was then compared to data collected in an identical fashion from golfers without such conditions. The results of our study show that there were no differences related to club handle design on impact force or impact location, club head velocity, or club head path and face angle. Wrist kinematic differences were minimal between handle designs. The differences that were significant (P less than 0.05) centered around the decreased ulnar deviation of the left hand that resulted when subjects used the BioCurve handle design, which also allowed greater resistance to torque than the straight grip club. In addition to collecting objective data, we asked subjects for their opinions of the two grips. As a whole, the normal group and the group with pathologic conditions noted more comfort, improved grip, and less shock transmission with the BioCurve handle. PMID- 1867338 TI - Quadriceps contusions. West Point update. AB - A 3 year study of 117 quadriceps contusions in West Point cadets was undertaken to document the effectiveness of a three-phased therapy program to return these young athletes to full activity with a normal knee range of motion and without recurrence of injury. The treatment protocol of this study was modeled after the 1973 West Point study of Jackson and Feagin with two major changes: 1) resting the injured leg in flexion (versus extension) and 2) emphasizing early flexion exercises (versus extension). Classification of contusions was based on knee range of motion at 12 to 24 hours after the injury (mild, greater than 90 degrees; moderate, 45 degrees to 90 degrees; severe, less than 45 degrees). The average disability time was 13 days for mild, 19 days for moderate, and 21 days for severe contusions. Myositis ossificans developed in 9% of cadets and was associated with five risk factors (knee motion less than 120 degrees, injury occurring during football, previous quadriceps injury, delay in treatment greater than 3 days, and ipsilateral knee effusion. PMID- 1867339 TI - Dynamic joint forces during knee isokinetic exercise. AB - This study analyzed forces in the tibiofemoral and patellofemoral joints during isokinetic exercise using an analytical biomechanical model. The results show that isokinetic exercise can produce large loads on these joints, especially during extension exercises. The tibiofemoral compressive force (4.0 body weight) is approximately equal to that obtained during walking but it occurs at 55 degrees of knee flexion. Anterior shear forces (resisting force to anterior drawer) exist during extension exercise at less than 40 degrees of knee flexion, with a maximum of 0.3 body weight. Posterior shear forces (resisting force to posterior drawer) exist during extension exercise at knee joint angles greater than 40 degrees and during the flexion portion of isokinetic exercise. The maximum posterior shear force is 1.7 body weight. The patellofemoral joint can encounter loads as high as 5.1 body weight which are 10 times higher than during straight leg raises. These results suggest that isokinetic exercise should be used cautiously in patients with knee lesions. PMID- 1867340 TI - Fatigue fracture of the ulna occurring in pitchers of fast-pitch softball. AB - We have reported three cases of fatigue fracture of the ulna in male pitchers of fast-pitch softball. To elucidate the etiology of injury, we first selected three healthy male and three healthy female pitchers from a well-trained college team and analyzed their forearm movement by high-speed cinematography. This showed slight flexion of the elbow joints during wind-up motion, dorsal flexion of the hand joints upon releasing the ball, and extreme pronation of the forearms during the follow-through. We then took 8 mm CT scanning sections of the forearms. Using these images, we investigated shapes and areas of cross-sections of the ulna and its cortical and cancellous bones from the elbow to the hand joints. Our results reveal that the shapes of the sections are significantly different from circles at around the center of the ulna, and the cross-sectional areas are smaller in the middle one-third of the ulna than in other parts. These observations imply that fatigue fractures of the ulna in pitchers of fast-pitch softball must be torsionally induced, tending to occur at the middle one-third of the bone. PMID- 1867341 TI - Traumatic subluxation of the hip resulting in aseptic necrosis and chondrolysis in a professional football player. PMID- 1867342 TI - Bilateral simultaneous rupture of the infrapatellar tendon in a recreational athlete. A case report. AB - Bilateral rupture of the infrapatellar tendons is a rare event in an otherwise healthy athletic individual. The event is usually quite severe and diagnosis can be readily made on a clinical examination. In the case presented here, predisposing factors consisted of an underlying patella alta and a long history of repetitive trauma to the knee. Prompt diagnosis and surgical repair will lead to a good functional result. PMID- 1867343 TI - Yellow fever: Victor, Victoria? Conqueror, conquest? Epidemics and research in the last forty years and prospects for the future. PMID- 1867344 TI - Ultrastructural localization of a protective 68,000 molecular weight antigen in Schistosoma mansoni. AB - Vaccination with SMW 68, an Mr 68,000 glycoprotein of Schistosoma mansoni, induces significant protection in mice against challenge schistosome infection. This resistance occurs without the use of adjuvants and without sensitizing animals to granuloma formation. Likewise, passive transfer of monoclonal antibody (MAb) 31-3B6 against SMW 68 confers partial protection against challenge infection. As a first step in understanding how the immune response to this molecule leads to resistance, SMW 68 was localized in three developmental stages of the parasite by immunoelectron microscopy using MAb 31-3B6 and polyclonal antisera raised against purified SMW 68. In cercariae and schistosomula, MAb 31 3B6 bound electron-dense granules within the head gland and similar granules in the preacetabular glands. In adult worms, SMW 68 or related antigens were found to be widely distributed in tissues. Binding of specific antisera was most pronounced in the gut and tegument of male worms, but less so in subtegumental muscles. We conclude that SMW 68 is presented to the immune system in various ways during parasite development. The protective protein or epitope is excreted, and presented on the surface and in the cytoplasm at various stages of the life cycle. The relationship of the location of this protein to its role in protective immunity is discussed. PMID- 1867345 TI - Comparison of the effects of a single dose and of four six-monthly doses of ivermectin on adult Onchocerca volvulus. AB - Adult Onchocerca volvulus worms, extracted from nodules of Guatemalans by collagenase digestion, were examined whole and by histological techniques. One group of persons received a single 150 micrograms/kg dose of ivermectin; two other groups (one with older and one with younger nodules) received four similar doses of ivermectin at 6-month intervals. For each group, there were comparable untreated controls. All nodules were removed six months after the last dose. After a single dose, the only significant difference from the controls was in the decreased proportion of female worms producing live microfilariae. After four doses, there were significant increases in the proportions of moribund/dead female worms and of live uninseminated females, when compared with the corresponding controls. There were also fewer male worms present, but this difference was not significant. Six months after the conclusion of the 4-dose regimen, the proportion of female worms producing live microfilariae was significantly lower than in the groups that had received a single dose. PMID- 1867346 TI - Cellular immune response analysis of patients with leptospirosis. AB - Peripheral blood mononuclear cells (PBMC) from acute leptospirosis patients with and without acute renal failure were studied in order to investigate the status of cellular immunity in this disease. We analyzed the lymphocyte subsets of leptospirosis patients by immunofluorescence and their responsiveness to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM). Additionally, we investigated the effect of the patients' sera on normal PBMC proliferative response. We observed a decrease in the CD3+ and CD4+ cell subsets in patients with and without acute renal failure, or in percentage values alone in those who had recovered from renal failure. An increase in the number of B lymphocytes was observed in all patients, compared with controls. This increase in B lymphocytes was seen even in patients who had recovered from renal failure, when the number of CD3+ and CD4+ lymphocytes had already returned to normal levels. The low PHA response observed only with lymphocytes from patients with acute renal failure suggests a suppressive effect. The proliferative response to PWM was comparable to controls, even in the patients with acute renal failure. This latter result and the expansion of the B cell number could be related to leptospiral-derived factor(s). We also showed that sera from patients with and without acute renal failure exerted some inhibitory activity on normal PBMC responses to PHA and PWM. Although the redistribution of lymphocyte subsets and the serum suppressor activity were related to acute renal failure and leptospiral factor(s), we suggest that the cellular immune system was not irreversibly affected, which is compatible with the good prognosis seen in the patients studied. PMID- 1867347 TI - Dissemination, replication, and trans-stadial persistence of Dugbe virus (Nairovirus, Bunyaviridae) in the tick vector Amblyomma variegatum. AB - The dissemination and replication of Dugbe (DUG) virus and its tissue tropisms in the tick vector Amblyomma variegatum were examined by immunohistochemical analysis using specific antibody, in situ hybridization with a viral complementary riboprobe, and infectivity assays of dissected tissues. Dugbe virus was localized in both unfed and feeding adults inoculated as nymphs or orally infected by capillary feeding, and in nymphs infected by capillary feeding. In non-feeding ticks, the main sites of DUG virus replication were the epidermis, hemocytes associated with loose connective tissue, and a small number of phagocytic digestive cells in the gut lumen. Virus infectivity in the hemolymph was associated entirely with hemocytes. Dugbe viral antigen or infectivity was not detected in the salivary glands until after the start of feeding. Viral titers in the salivary glands of feeding ticks were about ten-fold higher than in gut, ovary, or loose connective tissue. The level of infection decreased during molting and increased during feeding. Viral particles and pathologic effects were not detected in infected ticks. The primary site of trans-stadial persistence of DUG virus is the hemocytes. Tick hemocytes and other motile cells may be important in the transmission of persistent virus infection from one cell or organ to another by diapedesis. PMID- 1867348 TI - Significance of circumsporozoite-specific antibody in the natural transmission of Plasmodium falciparum, Plasmodium vivax, and Plasmodium malariae in an aboriginal (Orang Asli) population of central peninsula Malaysia. AB - Two hundred and seventy-five Orang Asli volunteers living in nine villages in the Pos Legap Valley of Perak State, peninsular Malaysia, participated in a prospective study designed to characterize the epidemiological, parasitological, and entomological characteristics of Plasmodium falciparum, P. vivax, and P. malariae malaria transmission. Prevalence rates for the three plasmodial species at initiation of the study ranged from 56% in the 0-4-year-old age group to 0% in individuals over the age of 40. Entomological surveys were conducted, enabling us to determine mosquito salivary gland-positive rates and entomological inoculation rates of 1.2 infectious mosquito bites per person per month for P. falciparum, 2.4 for P. vivax, and 0.3 for P. malariae. Cumulative incidence rates over the 16 weeks of the study, following radical cure of all volunteers, were 22.5% for P. falciparum, 12.7% for P. vivax, and 1.5% for P. malariae. The median baseline antibody titer against the immunodominant repetitive B cell epitope of P. falciparum or P. vivax circumsporozoite protein was significantly higher for volunteers who did not become parasitemic. Volunteers were selected for further study if they had evidence of being challenged with P. falciparum sporozoites during the study, based on a two-fold or greater increase in antibody titer against the immunodominant repetitive B cell epitope of the circumsporozoite protein. Resistance to infection was seen in six of 10 individuals who had high (greater than 25 OD units) baseline ELISA titers, compared with only three of 24 individuals who had low baseline ELISA titers (chi 2 P less than 0.02). A similar analysis for P. vivax did not show a significant correlation. PMID- 1867349 TI - Age-dependent acquired protection against Plasmodium falciparum in people having two years exposure to hyperendemic malaria. AB - An epidemiologic study of susceptibility to frequent and high-grade parasitemia by Plasmodium falciparum revealed that age-dependent acquired protection developed within a two-year period of exposure to hyperendemic infection pressure. The study was conducted in a single village in northeastern Irian Jaya, Indonesia, where half the residents were native to the province and the other half were transmigrants from areas of Java, where there is little or no malaria transmission. Five separate measures of susceptibility to the asexual parasitemia of falciparum malaria were derived from results of four months of biweekly surveillance of 240 volunteers. Increasing protection as a function of age among the Javanese was a consistent pattern among the five estimates of susceptibility. These age-dependent functions of protection were quantitatively parallel to those among life-long residents of Irian Jaya. When humoral immune responsiveness to ring-infected erythrocyte surface antigen (RESA) was measured by ELISA, a similar pattern emerged; the relative level of antibody to RESA increased as parallel functions of age among the two subpopulations. Acquired protective immunity against P. falciparum was not the cumulative product of many years of heavy exposure to antigen. Instead, the full benefit of protection appeared to develop quickly. The degree of protection was governed by recent exposure and age, independent of history of chronic heavy exposure. PMID- 1867350 TI - Clustering of malaria infections within an endemic population: risk of malaria associated with the type of housing construction. AB - The occurrence of malaria infections due to Plasmodium vivax and P. falciparum was monitored in a population of 3,023 people living in six contiguous villages in Kataragama, an area of endemic malaria in southern Sri Lanka, over a period of 17 months. The annual incidence of malaria in this population during the study period was 25.8%. Malaria attacks were clustered, occurring more frequently than expected in certain individuals and housing groups and less frequently than expected in others. In one of these villages, the distribution of cases was examined in relation to locality and to the type of house construction. There was a strong association between the malaria incidence and house construction, independent of location. The risk of getting malaria was greater for inhabitants of the poorest type of house construction (incomplete, mud, or cadjan (palm) walls, and cadjan thatched roofs) compared to houses with complete brick and plaster walls and tiled roofs. Houses that were better constructed had a significantly lower malaria incidence rate (10.5%) than those that were poorly constructed (21.2%; P less than 0.01, by Student's t-test). There was also a significantly higher number of indoor resting mosquitoes collected from the poorly constructed houses than from those better constructed; the average (geometric mean) of mosquito densities found in houses of better versus poor construction were 0.97 and 1.89 per collection in the dry season, and 1.95 and 3.42 per collection in the wet season, respectively (P less than 0.05 in both seasons). This indicated that the higher malaria risk associated with poorly constructed houses was at least partly due to higher human-mosquito contact among their inhabitants. PMID- 1867351 TI - Neuropsychiatric side effects after the use of mefloquine. AB - This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended. PMID- 1867352 TI - Folliculosebaceous cystic hamartoma. A distinctive malformation of the skin. AB - Five examples of a distinctive sebaceous malformation, designated "folliculosebaceous cystic hamartoma," form the basis of this study. Criteria are proposed for specific diagnosis of this hamartoma and for differentiation of it from sebaceous gland hyperplasia, steatocystoma, dermoid cyst of skin, and sebaceous trichofolliculoma. PMID- 1867353 TI - The development of a reproducible immunocytochemical technique for demonstrating colocalized cutaneous antigens. AB - A number of double immunocytochemical labeling techniques are available that allow simultaneous identification of two antigens in one tissue section. Those most commonly used are (a) the acid elution method, which uses acid buffer to remove one set of antibodies, thus allowing a second set to be applied; (b) the use of noncross-reacting combinations of immunoglobulin subclass and subclass specific antibodies; and (c) application of the diaminobenzidine (DAB) reaction product as an antibody-blocking reagent, preventing cross-reaction of one set of antibodies with those of a second labeling method. We assessed each technique, using a variety of immunoenzyme methods, for the ability to label antigens that are anatomically separate in one tissue section and those that are colocalized on the same cell surface. Acid elution methods increased antibody cross-reaction. The use of immunoglobulin subclass antibodies resulted in inferior staining. The DAB blocking method, using peroxidase antiperoxidase (DAB substrate) and alkaline phosphatase antialkaline phosphatase (APAAP) (fast red substrate) optimally labeled non colocalized antigens. The substitution of fast blue as the APAAP substrate proved optimal for colocalized antigens, producing brown and blue single-labeled and black double-labeled cells. PMID- 1867354 TI - Histologic evolution of basal cell carcinoma recurrence. AB - The biological behavior and appropriate therapy of recurrent basal cell carcinoma (BCCA) is controversial, with some studies suggesting that this tumor becomes more aggressive with each recurrence, and other studies indicating that the majority are aggressive from the onset. The authors studied the histologic evolution of BCCA by comparing 29 original tumors with their subsequent recurrences to determine if there were any predictable histologic changes. There were borderline statistically significant changes only in degree of fibrosis, prominence of nucleoli, and mitotic frequency. There were no statistically significant changes in any of the other parameters, including those that were shown previously to be predictive of recurrence or aggressive behavior. The results of this study clearly indicate that the majority of recurrent BCCAs are aggressive from the onset, and that in many cases this can be predicted from the histomorphology of the original tumor. PMID- 1867355 TI - Cell degeneration in alopecia areata. An ultrastructural study. AB - The morphology and prevalence of different forms of cell degeneration in hair follicles in acute alopecia areata were investigated. In addition to apoptosis and necrosis, a third morphological pattern of cell degeneration, dark-cell transformation, was evident. Fifteen patients with untreated acute alopecia areata and three normal adults without hair loss were studied. Electron microscopy revealed that although apoptosis of outer root sheath keratinocytes produces normal hair follicle involution (catagen), increased levels of apoptosis, necrosis, and dark-cell formation appear to be related to the pathology of alopecia areata. Although cell degeneration was generally restricted to keratinocytes of the lower follicle, melanocytes, Langerhans' and dermal papilla cells were also affected. Keratinocytic degeneration may affect layers of matrix cells in alopecia areata, unlike the apoptosis of scattered outer root sheath cells in normal catagen. The extent of cell death suggests a pathological rather than a physiological event in alopecia areata. PMID- 1867356 TI - Scanning electron microscopic features of Kaposi's sarcoma. AB - In order to clarify the three-dimensional structure of Kaposi's sarcoma (KS) five cases of KS of the skin were observed with a scanning electron microscope (SEM). KS lesions were investigated both in vascular and spindle cell areas and were compared with similar areas observed by light microscopy. KS appears as a spongelike neoplasm consisting of irregular vascular channels lacking endothelial cells and well-developed basement membranes. Vascular spaces and vascular slits are packed with numerous red blood cells (RBCs). SEM features of KS share some similarities with those of hemangiopericytoma, a vascular tumor composed of mature endothelial cells surrounded by pericytes. These findings are consistent with the hypothesis according to which the proliferating cells of KS are viewed as immature endothelial cells with partial differentiation into pericytes. PMID- 1867357 TI - Morsicatio buccarum et labiorum (excessive cheek and lip biting). AB - In some individuals habitual cheek and lip biting becomes a fixed neurosis. Pieces of oral mucosa are actually torn free from the surface, producing a distinctive clinical appearance termed morsicatio buccarum et labiorum. Sometimes it may be confused with other dermatological disorders involving the oral mucosa, and can lead to misdiagnosis. Most patients with this condition are unaware of their habit and will not aid in the diagnosis. We suggest that the histopathological features of this condition are distinctive, if not pathognomonic, and that an accurate diagnosis should be rendered if a biopsy sample is taken. Two cases are reported herein that were originally misdiagnosed as pemphigus, one of which resulted in complications of improper oral corticosteroid use. PMID- 1867358 TI - Malignant hair matrix tumor ("malignant trichoepithelioma") arising in the setting of multiple hereditary trichoepithelioma. AB - An unusual adnexal tumor on the scalp of a 59-year-old woman with hereditary trichoepithelioma is reported. After the initial removal, the tumor recurred twice during a 4-year period. Mohs micrographic surgery resulted in full excision of the lesion. Two years later there was no evidence of recurrence. Histologic examination of the tumor showed it to merge with adjacent areas of classic trichoepithelioma. The tumor showed cytologic atypia, mitotic figures, necrosis, deep infiltration, and features of pilar differentiation including clear cells, reminiscent of cells of the follicular outer root sheath, and focal shadow-cell formation. The differential diagnosis of this malignant follicular neoplasm included pilomatrix carcinoma and basal-cell carcinoma with matrical differentiation. The unique clinicopathologic features, however, raised consideration of a "malignant trichoepithelioma." PMID- 1867359 TI - Systematized progradient multiple combined melanocytic and blue nevus. AB - A 44-year-old woman was diagnosed as having unilateral multiple progradient pigmented macules and papules of the upper extremity and adjacent part of the back. Microscopically increased amounts of melanin and melanocytes in the basal layer of the epidermis in the early developmental stage of macules were seen. Combinations of blue nevus with junctional or compound nevus or with a simple proliferation of melanocytes in the epidermis were present in the papules. The question of prognosis is discussed. PMID- 1867361 TI - Is dermatology a trivial specialty? PMID- 1867360 TI - Malignant mesothelioma presenting as Sister Joseph's nodule. AB - We report a rare case of malignant peritoneal mesothelioma in which the patient presented with umbilical tumor involvement. This case is also compared with other cases of umbilical neoplasm. PMID- 1867362 TI - Dermatology is a profound specialty that must not be trivialized. PMID- 1867364 TI - The death of Heracles. An inquest. PMID- 1867363 TI - The prohibition of tattooing in New York City. PMID- 1867365 TI - Atypical melanocytic proliferations. PMID- 1867366 TI - [Infectious complications due to central venous polymeric catheters]. AB - Due to the multitude of invasive procedures of today's intensive care medicine, infections from central venous catheters have gained increasing attention. The incidence of bacteremias arising from such devices ranges from less than 0.1 to 0.6 cases per 100 catheter-days. Factors influencing the incidence of catheter associated infections are related to patient characteristics as well as the purpose and material of the catheter. Silicone catheters seem to carry a lower risk of infection than common polytetrafluorethylene catheters. The most frequently isolated bacteria in catheter-associated infections are coagulase negative and coagulase-positive staphylococci, enterococci, and pseudomonas species. Septicemias due to Candida albicans frequently complicate the course of immune-compromised patients receiving total parenteral nutrition (TPE). Catheter associated bacteremias (CAB) can arise from the contaminated hub, from which pathogens migrate intraluminally to the blood stream. When the catheter entry site is infected, bacteria may reach the blood via the extraluminal route and cause septicemia. Endemic outbreaks of CAB often originate from contaminated infusion fluids. As the clinical presentation of "catheter infections" is often uncharacteristic and insidious, a definite diagnosis depends on bacteriological examination of the catheter. Quantitative and semiquantitative culture techniques of the catheter tip help to distinguish colonization from contamination by numbers of colony-forming units per milliliter culture medium. Preliminary results can be obtained by simple Gram or acridine-orange staining of the catheter tip. The most important prophylactic measures to prevent CAB are strictly aseptic conditions when catheters are placed and meticulous care thereafter, preferably by specially trained nurses or "TPE teams".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867367 TI - [The effect of flumazenil on alfentanyl-induced respiratory depression]. AB - Use of the benzodiazepine antagonist flumazenil may inhibit the effects of benzodiazepines in a competitive manner. The only known partially agonistic effect of flumazenil is a weak anticonvulsive action at high doses. However, reports have claimed that flumazenil reduces the MAC of isoflurane in animal studies. Other reports have found that antagonizing midazolam-induced sedation or anesthesia by flumazenil led to an increase in respiratory depression. The aim of this study was to examine whether flumazenil i.v. increases fentanyl-induced respiratory depression. METHODS. In two separate sessions, ten healthy young volunteers were given either 0.0027 mg/kg fentanyl alone or 0.0027 mg/kg and 1 mg flumazenil i.v. over 4 min each time. The CO2 rebreathing method was used to determine the ventilatory response. RESULTS. Fentanyl alone brought about a significant reduction in CO2 response, characterized by a shift to the right and a decrease in the slope of the rebreathing curve (from 1.95 +/- 0.76 l.min-1.mmHg 1 to 0.86 +/- 0.53 l.min-1.mmHg-1). The infusion of additional flumazenil caused similarly significant respiratory depression (from 2.21 +/- 1.0 l.min-1.mmHg-1 to 0.77 +/- 0.38 l.min-1.mmHg-1). In both groups changes persisted for at least 120 min. No statistically significant differences between the two groups could be detected. CONCLUSION. Flumazenil does not enhance fentanyl-induced respiratory depression. Flumazenil's weak, partially agonistic action is therefore of no clinical importance. PMID- 1867368 TI - [The prognostic value of the delayed cutaneous immune reaction following multiple trauma in comparison with other clinical parameters]. AB - Infection is a frequent cause of morbidity and mortality after multiple trauma. Although impaired immune function has been assumed to be associated with the development of infection and sepsis in trauma victims, its predictive role is still controversial. In a prospective study, the predictive value of the immunological in vivo response to intradermally applied recall antigens was compared with serial determinations of routine parameters. PATIENTS AND METHODS. Using the commercially available Multitest device, the cutaneous delayed-type hypersensitivity (DTH) response to seven standardized recall antigens was sequentially tested at defined time intervals in 35 mechanically ventilated multiple-trauma patients (4 females, 31 males). Routine clinical and laboratory parameters (FiO2, lactate, creatinine, platelet count, absolute and differential white blood cell (WBC) count) were determined every day. Injury severity scores (ISS), infections, and intensive care unit (ICU) mortality were prospectively documented by the same investigator. RESULTS AND DISCUSSION. The overall ICU mortality was 23%. In survivors, the mean ISS was 29.5, in nonsurvivors 38.9 (P less than 0.05). Mortality significantly increased in association with sepsis. Interestingly, the DTH response and severity of the trauma did not show any interdependence. Immediately after ICU admission, DTH testing failed to correlate with either infection or mortality: most of the multiply traumatized patients were anergic on initial skin testing. In the early posttraumatic stage, the serum levels of creatinine or lactate, lymphocyte and promyelocyte counts, and FiO2 proved to be more reliable predictors. In the later course, however, a good correlation was found between sequential skin test results and the development of infection. Beginning on the 4th day after trauma, DTH scores below 5 mm defined a population with a high incidence of developing a clinically important septic episode. In conclusion, lactate, FiO2, and WBC counts are early indicators of an impending poor outcome, whereas the skin test response is not. In the later course, however, the sequentially determined DTH response may substantially contribute to the identification of multiple-trauma patients at increased risk of infection. PMID- 1867369 TI - [Postoperative urinary retention]. AB - In 359 patients 371 operations were performed under general or regional anesthesia, and these were followed up with regard to anesthesiological technique, postoperative course and voiding of the bladder. Patients under 15 years of age, with severe incontinence or with a bladder catheter were excluded from the study. The surgical specialties were general surgery, orthopaedics, gynecology, ENT and ophthalmology. If any patient had not urinated by 6-10 h postoperatively and was found to have a full bladder on palpation, urinary retention was diagnosed. There were 75 patients (20%) who had urinary retention, significantly fewer women than men (p less than 0.025), and men under 35 years old had significantly less retention than older men (p less than 0.0025). The anesthesiological technique is an important factor in postoperative urinary retention: spinal anesthesia with tetracaine and adrenaline caused significantly more retention than spinal anesthesia with lidocaine 5% (p less than 0.005), and more than epidural or general anesthesia (p less than 0.005). No significant difference concerning urinary retention was found regarding surgical specialty, emergency operations, morphine or adrenaline added to tetracaine for spinal anesthesia, amount of local anesthetics used for epidural anesthesia or between spinal anesthesia with lidocaine 5% and epidural anesthesia with mepivacaine. Once urinary retention is diagnosed, conservative (privacy, relaxation exercises, getting up) or medical treatment (propyphenazone + hexahydroadiphenine (Spasmocibalgin), carbamoyl choline chloride) should be given. Catheterization should be performed only as a last resort. PMID- 1867371 TI - [An unnoticed dislocation of the dens axis in a patient with primary chronic polyarthritis undergoing intensive therapy]. AB - Involvement of the cervical spine is seen in 40%-60% of all patients with rheumatoid arthritis. Consequences are instability of the upper cervical column with pain and neurological deficits, in some cases tetraplegia, and sudden death. From this reason special care has to be taken in the management of those patients, even when they are comatose or anesthetized, to avoid sudden spinal cord compression with irreversible neurological deficits. We report a 49-year-old female with a history of rheumatoid arthritis for more than 10 years. Because of an adhesive ileus complicated by septicemia, she underwent abdominal surgery twice followed by prolonged mechanical ventilation under high doses of sedative drugs. After reduction of the tranquilizer doses tetraplegia with respiratory insufficiency was found. Neurophysiological and X-ray examinations showed spinal cord compression due to dislocation of the odontoid process, a rare but typical complication in patients with rheumatoid arthritis. It was not possible to determine the date of the dislocation, but it might have been caused by intubation or respositioning. Although the patient underwent immobilization and surgical fusion of the upper cervical spine, there was no improvement in the neurological status and she died 5 months later. In patients with advanced rheumatoid arthritis a detailed medical history, clinical examination, and radiography are necessary before general anesthesia or intensive care with intubation is considered. If an unstable cervical spine is suspected, intubation should be performed by fiberoptic technique under light sedation. Regional anesthesia should be preferred over general anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867370 TI - [Bronchial rupture. Diagnosis and therapy of a rare complication of the use of double-lumen tubes]. AB - For anesthesia during thoracic surgery, it is common to use a double-lumen endotracheal tube for one-lung ventilation. Double-lumen tubes protect the bronchial system of the healthy lung from being occluded by blood or pus coming from the operated lung. Therefore, in cases of lung abscess, bronchial hemorrhage, lung cyst, or localized lung infection the use of a double-lumen tube is advisable. Facilitating operation and reduced operating time are further advantages of intubation with a double-lumen tube for independent ventilation of both lungs. Due to the rigidity of these tubes, however, there are disadvantages such as injuries to the trachea and bronchial system. We report a case of rupture of the left main bronchus after insertion of a Carlens tube. The intraoperative symptoms of airway leakage are demonstrated, the process of locating and repairing the injury is described. In our case the postoperative course was not complicated; the patient left the hospital 10 days after operation. Causes of bronchial rupture, its therapy, and prophylactic measures are also discussed. PMID- 1867372 TI - [Malignant hyperthermia in a child with acute lymphatic leukemia]. AB - A 5-year-old boy with acute lymphatic leukemia in remission developed signs of malignant hyperthermia (MH) during general anesthesia for removal of a central venous access port. The anesthetic procedure for implantation of the port 17 months before had been uneventful despite use of the same triggering agents, halothane and succinylcholine. Meanwhile, the patient had received chemotherapy (COALL-03-85). The first sign of MH was masseter spasm following succinylcholine; then tachycardia, acidosis, myoglobinuria, and CPK elevation (8953 IU) appeared. There was only moderate temperature elevation to 37.8 degree C. Rapid improvement and complete recovery occurred after dantrolene i.v. The patient's father was found to have undiagnosed muscle pain and an elevated CPK level. An in vitro contracture test with halothane and caffeine revealed susceptibility to MH and supported the patient's diagnosis and genetic predisposition. Referring to several other cases in the literature concerning MH in patients with lymphomas and leukemias, a possible correlation between the two diseases is discussed. As the MH crisis in our patient was most probably genetic in origin, a common acquired cause such as a viral infection seems less probable. We do not believe the chemotherapy our patient received between the two anesthetics was the cause since about one-half of the patients in the literature had not had chemotherapeutic pretreatment at the time of the MH crisis. We believe that a common genetic predisposition is the most likely link between the two diseases. In any case, patients with leukemias and lymphomas should be monitored very carefully for symptoms of MH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867373 TI - [Intraoperative anaphylactic shock due to a latex allergy]. AB - Delayed hypersensitivity to rubber chemicals is well known, but there has been an increasing number of reports of immediate-type hypersensitivity due to latex causing contact urticaria, angioedema, bronchial asthma, and anaphylactic shock in adults. We report a 10-year-old boy who developed anaphylactic shock during surgery due to surgical gloves containing latex. The patient was atopic and had a history of neurodermatitis and localized angioedema on exposure to rubber. There had been two previous uneventful surgical procedures. Thirty-five minutes after induction of anesthesia and 5 min after laparotomy for appendectomy there was an acute onset of increased airway pressure, oxygen desaturation, and profound hypotension. The circulation and gas exchange stabilized after treatment with oxygen, intravenous fluids, epinephrine, H1 and H2 blockers, aminophylline, and methylprednisolone. A positive skin test and RAST revealed a latex allergy. Latex can cause life-threatening allergic reactions in patients with a history of rubber allergy or frequent exposure to latex products. PMID- 1867374 TI - Purification and characterization of three toxins and two agglutinins from Abrus precatorius seed by using lactamyl-Sepharose affinity chromatography. AB - Three toxins, abrin-I, -II, and -III, and two agglutinins, APA-I and -II, were purified from the seeds of Abrus precatorius by lactamyl-Sepharose affinity chromatography followed by gel filtration and DEAE-Sephacel column chromatography. Abrin-I did not bind on DEAE-Sephacel column chromatography and the bound abrin-II, abrin-III, APA-I, and APA-II were eluted with a sodium acetate gradient. The identity of each protein was established by sodium dodecylsulfate-polyacrylamide gel electrophoresis and isoelectric focusing. The relative molecular weights are abrin-I, 64,000; abrin-II and abrin-III, 63,000 each: APA-I, 130,000; and APA-II, 128,000. Isoelectric focusing revealed microheterogeneity due to the presence of isoforms in each protein. Toxicity and binding studies further confirmed the differences among the lectins. The time course of inhibition of protein synthesis in thymocytes by the toxins showed lag times of 78, 61, and 72 min with Ki's of 0.55, 0.99, and 0.74 ms-1 at a 0.63 nM concentration of each of abrin-I, -II, and -III, respectively. A Scatchard plot obtained from the equilibrium measurement for the lectins binding to lactamyl Sepharose beads showed nonlinearity, indicating a cooperative mode of binding which was not observed for APA-I binding to Sepharose 4B beads. Further, by the criterion of the isoelectric focusing profile, it was shown that the least toxic abrin-I and the highly toxic abrin-II isolated by lactamyl-Sepharose chromatography were not retained on a low-affinity Sepharose 4B matrix, which signifies the necessity of using a high-affinity matrix for the purification of the lectins. PMID- 1867375 TI - Functionalized membrane supports for covalent protein microsequence analysis. AB - Methods were developed for high yield covalent attachment of peptides and proteins to isothiocyanate and arylamine-derivatized poly(vinylidene difluoride) membranes for solid-phase sequence analysis. Solutions of protein or peptide were dried onto 8-mm membrane disks such that the functional groups on the surface and the polypeptide were brought into close proximity. In the case of the isothiocyanate membrane, reaction between polypeptide amino groups and the surface isothiocyanate moieties was promoted by application of aqueous N methylmorpholine. Attachment of proteins and peptides to the arylamine surface was achieved by application of water-soluble carbodiimide in a pH 5.0 buffer. Edman degradation of covalently bound polypeptides was accomplished with initial and repetitive sequence yields ranging from 33 to 75% and 88.5 to 98.5%, respectively. The yields were independent of the sample load (20 pmol to greater than 1 nmol) for either surface. Significant loss of material was not observed when attachment residues were encountered during sequence runs. Application of bovine beta-lactoglobulin A chain, staphylococcus protein A, or the peptide melittin to the isothiocyanate membrane allowed for extended N-terminal sequence identification (35 residues from 20 pmol of beta-lactoglobulin). A number of synthetic and naturally occurring peptides were sequenced to the C-terminal residue following attachment to the arylamine surface. In one example, 10 micrograms of bovine alpha-casein was digested with staphylococcal protease V8 and the peptides were separated by reverse-phase chromatography. Peptide fractions were then directly applied to arylamine membrane disks for covalent sequence analysis. From as little as 2 pmol of initial signal it was possible to determine substantial sequence information (greater than 10 residues). PMID- 1867376 TI - Stabilized procedure for the determination of urokinase fibrinolytic potency. AB - A stabilized procedure for the determination of urokinase (UK) fibrinolytic potency is described in which method response is dependent on urokinase concentration and independent of normal variation in assay parameters. The method is a selective stability-indicating procedure for UK active enzyme. It is suitable for evaluation of both high molecular weight as well as low molecular weight urokinase fractions and is calibrated against the World Health Organization International Reference Preparation for UK code 66/46 using a biological six-point parallel line log-log dose-response approach where sample and standard are compared under essentially identical conditions. High method stability and sensitivity are achieved through the use of appropriate levels of purified human plasminogen and human plasma (source of fibrinogen) as primary and secondary substrates, respectively. Method precision versus house reference standard (%RSD less than or equal to 2%) is suitable for research and pharmaceutical purposes. The absolute UK potency reference plane established in the calibrated procedure is equivalent to that established by other investigators in the fibrinolytic field. PMID- 1867377 TI - Trypsin inhibitor paradoxically stabilizes trypsin activity in sodium dodecyl sulfate, facilitating proteolytic fingerprinting. AB - Normally trypsin has negligible activity after being dissolved in sodium dodecyl sulfate (SDS), and so it has had little utility for proteolytic fingerprinting during gel electrophoresis. Here it is demonstrated that trypsin retained activity in SDS if it was first complexed to either of two soybean-derived protease inhibitors: trypsin inhibitor (Kunitz) or trypsin-chymotrypsin inhibitor (Bowman-Birk). The inhibitors alone did not cause proteolysis. Heating or acidification in SDS inactivated the inhibitor-dependent tryptic activity, as did prior treatment with tosyl lysine chloromethyl ketone, a covalent affinity reagent for trypsin. Quenching of samples with acid at intervals prior to gel electrophoresis revealed that proteolysis did not occur in sample buffer (pH 6.8), but only at higher pH and during gel electrophoresis. Exposure of trypsin to SDS prior to addition of trypsin inhibitor resulted in an irreversible loss of activity with a half-life of about 10 s. It is proposed that the trypsin inhibitors stabilize trypsin by retarding its denaturation in SDS. The substrate for these experiments was the alpha subunit of the Na,K-ATPase. The same pattern of Na,K-ATPase fragments was obtained with bovine and porcine trypsin and with rat and porcine Na,K-ATPases. Different fragments resulted when chymotrypsin or elastase were substituted for trypsin; these proteases were active in the absence of an inhibitor, and were not markedly stabilized by interaction with soybean trypsin-chymotrypsin inhibitor (Bowman-Birk). PMID- 1867378 TI - Determination of copper in urine and serum by gas chromatography-mass spectrometry. AB - A stable isotope dilution gas chromatography-mass spectrometry method using enriched 65Cu as an internal standard is described for the determination of Cu in urine and serum. Chelating agents N,N'-ethylenebis-(trifluoroacetylacetoneimine) [H2(enTFA2)] and lithium bis(trifluoroethyl)dithiocarbamate [Li(FDEDTC)] were used and evaluated for memory effect. H2(enTFA2) did not show any appreciable memory effect, whereas Li(FDEDTC) was found to have a strong memory effect. Overall precision of 1.6% was obtained for determining Cu isotope ratios at a 10 ng level using H2(enTFA2). Cu concentrations in the National Institute of Standards and Technology (NIST) reference materials, freeze-dried urine SRM 2670, and human serum SRM 909 determined using the H2(enTFA2) chelating agent were in good agreement with the NIST-certified values. Isotope ratios determined by gas chromatography-mass spectrometry on samples with altered isotopic composition were in good agreement with the inductively coupled plasma-mass spectrometry data. PMID- 1867380 TI - Resolution of 16 to 20 chlorophyll-protein complexes using a low ionic strength native green gel system. AB - Conventional native "green gel" systems resolve at most 10 chlorophyll-protein complexes from thylakoid membranes of higher plants and green algae. Such analyses suggest a simplicity of the thylakoid membrane that is not supported by a growing body of evidence on the heterogeneity of photosystems I and II (PSI and PSII) and their associated antennae (LHCI and LHCII). We report here the development and characterization of a low ionic strength native "green gel" system that resolves from 16 to 20, mostly large chlorophyll-protein complexes from a variety of higher plant and green algal species with very little release of free pigment. In Chlamydomonas, this system resolves multiple PSI-LHCI complexes, multiple PSII-LHCII complexes, four oligomeric LHCII complexes, as well as several low electrophoretic mobility reaction center complexes, and a number of small complexes. We have obtained similar resolution with a large number of higher plant and green algal species. We also demonstrate how this system can be used as a sort of "fingerprinting" technique to distinguish thylakoids of different species, and for the analysis of photosynthetic mutants, using the chlorophyll b-less chlorina f2 mutant of barley as an example. PMID- 1867381 TI - Synthesis of methyl 5-O-trans-feruloyl-alpha-L-arabinofuranoside and its use as a substrate to assess feruloyl esterase activity. AB - A synthetic scheme was developed for the production of methyl 5-O-trans-feruloyl alpha-L-arabinofuranoside (FA-Ara) in gram quantities. This molecule accurately models the chemical attachment of ferulic acid to polysaccharides found in cell walls of plants in the Gramineae family. It is therefore a realistic substrate that can be used to monitor feruloyl esterase activity. Ultraviolet spectral analysis indicated that FA-Ara has an absorption maximum distinct from the hydrolytic product, ferulic acid (FA), over a wide range of solution pH values. The log molar extinction coefficient ranges from 4.16 to 4.36 for FA-Ara and 4.16 to 4.33 for FA depending upon the pH of the buffered solution. Consequently a convenient spectrophotometric assay can be utilized to monitor esterase activity. Three different methods were developed for using this model substrate to assess esterase activity, including thin-layer chromatography, a spectrophotometric assay, and the use of high-performance liquid chromatography. PMID- 1867379 TI - A carbohydrate-directed heterobifunctional cross-linking reagent for the synthesis of immunoconjugates. AB - A novel, highly water-soluble, heterobifunctional cross-linking reagent, S-(2 thiopyridyl)-L-cysteine hydrazide (TPCH), was synthesized which contains a hydrazide moiety for coupling to aldehyde groups generated in the carbohydrate residues of antibodies by mild periodate oxidation, and a pyridyl disulfide moiety for coupling to molecules with a free sulfhydryl group. Since the carbohydrate moieties are distal to the antigen binding region of antibodies, derivatization with this cross-linker minimizes impairment of the antigen binding function. Derivatization of the human monoclonal IgM antibody 16-88 against human colon carcinoma cells with as many as 16 TPCH cross-linker molecules did not impair its antigen binding capability. Using mild oxidation conditions for antibody derivatization, sialic acid residues were identified as attachment sites for the cross-linker molecules, since after desialylation of antibody 16-88 by neuraminidase virtually no cross-linker molecules could be incorporated. Comparison of TPCH with S-(2-thiopyridyl)mercaptopropionic acid hydrazide and S (2-thiopyridyl)-L-cysteine, two related cross-linking reagents, revealed that TPCH is most efficiently incorporated into periodate-treated antibody. Based on the structural differences of the cross-linkers, the more efficient incorporation of TPCH appears to be a function of the presence of a hydrazide moiety with an adjacent amino group. When three to four molecules of pyridyl disulfide derivatized barley toxin were coupled to TPCH-derivatized antibody 16-88, the antigen binding capability remained uncompromised. In addition, no significant impairment of toxin activity upon coupling to the antibody was observed. Based on these data, TPCH may be very useful for the synthesis of immuno-conjugates with no or only minimal impairment of the antigen binding function. PMID- 1867382 TI - Photochemical cis-trans isomerization of furylacryloylpeptides and their different kinetic behavior as substrates for carboxypeptidase Y. AB - Furylacryloyl substrates used in kinetic measurements of proteolytic enzymes are shown to cis-trans photoisomerize quickly in plain daylight. The enzymatic transformation of the two forms is sufficiently different to cause problems for such measurements without careful protection against light. PMID- 1867383 TI - Synthesis of a reagent for fluorescence-labeling of vitamin D and its use in assaying vitamin D metabolites. AB - The fluorogenic dienophile 1,2,4-triazoline-3,5-dione with a highly fluorescent quinoxalinone group at the 4-position (DMEQ-TAD) was synthesized and exploited as a reagent to assay vitamin D metabolites. 25-Hydroxyvitamin D3, 1 alpha,25 dihydroxyvitamin D3, and 24(R),25-dihydroxyvitamin D3 reacted quantitatively with DMEQ-TAD when the two substrates were mixed in dichloromethane at room temperature to yield the corresponding 6,19-cycloadduct. The reaction was very fast so that 1 alpha,25-dihydroxyvitamin D3 at a concentration as low as 10(-8) M could be quantitatively labeled with the fluorescent reagent within 30 min at room temperature. With this reagent, down to 10 fmol of vitamin D metabolites could be quantified linearly. The detection limit of the labeled vitamin D using high-performance liquid chromatography was usually about 1 fmol. Thus, it was shown in a model system that the fluorometric method using the new reagent (DMEQ TAD) can be applied to the assay of the three major vitamin D metabolites in 1 ml of plasma. This is the first practical fluorometric method for assaying the active vitamin D metabolite. PMID- 1867384 TI - Protein secondary structure from Fourier transform infrared spectroscopy: a data base analysis. AB - An infrared (ir) method to determine the secondary structure of proteins in solution using the amide I region of the spectrum has been devised. The method is based on the circular dichroism (CD) matrix method for secondary structure analysis given by Compton and Johnson (L. A. Compton and W. C. Johnson, 1986, Anal. Biochem. 155, 155-167). The infrared data matrix was constructed from the normalized Fourier transform infrared spectra from 1700 to 1600 cm-1 of 17 commercially available proteins. The secondary structure matrix was constructed from the X-ray data of the seventeen proteins with secondary structure elements of helix, beta-sheet, beta-turn, and other (random). The CD and ir methods were compared by analyzing the proteins of the CD and ir databases as unknowns. Both methods produce similar results compared to structures obtained by X-ray crystallographic means with the CD slightly better for helix conformation, and the ir slightly better for beta-sheet. The relatively good ir analysis for concanavalin A and alpha-chymotrypsin indicate that the ir method is less affected by the presence of aromatic groups. The concentration of the protein and the cell path length need not be known for the ir analysis since the spectra can be normalized to the total ir intensity in the amide I region. The ir spectra for helix, beta-sheet, beta-turn, and other, as extracted from the data-base, agree with the literature band assignments. The ir data matrix and the inverse matrix necessary to analyze unknown proteins are presented. PMID- 1867385 TI - Development of the nuclei and cell migration in the medulla oblongata. Application of the quail-chick chimera system. AB - We have tried to obtain new insight into the development of the medulla oblongata by using the quail-to-chick chimera system. Five types of isotopic and isochronic grafts were carried out, between quail and chick embryos, at the 10- to 12-somite stage: exchanges of (I) the entire myelencephalon, (II) the dorsal half of the myelencephalon, (III) the ventral half of the myelencephalon, (IV) the right half of the myelencephalon and (V) the dorsal quarter of the myelencephalon. Before analyzing the chimeric embryos, we studied the ontogeny of the various nuclei in the medulla oblongata of normal birds. The first appearance of nuclei in quail embryos preceded in many cases that of their chick counterpart by 12 to 24 h. The adult pattern of the nuclei was established by E8 in quail and E9 in chick. Similarly, during early development of chimeras, the migration of quail cells began earlier than that of chick cells. This shows that the species specific temporal sequence of proliferation and migration is not significantly altered by transplantation into the host. The possibility of grafting selectively the ventral or dorsal half of the neural tube allowed us to distinguish the fate of the cells belonging respectively to the alar and the basal plate. The nuclei with a total or partial motor function, such as the nucleus nervi abducentis, the nucleus nervi facialis, the nucleus nervi glossopharyngei and the nucleus motorius dorsalis nervi vagi, have either an exclusive or predominant origin from the basal plate. In contrast, the nuclei with essentially or exclusively sensory components (i.e., nucleus angularis, nucleus laminaris, nucleus magnocellularis) arise from the alar plate. The reticular formation such as the nucleus reticularis gigantocellularis and the nucleus reticularis subtrigeminalis was strikingly mixed, with both alar and basal plate origin of neurons. Active dorsoventral migrations of cells originating migrations from the dorsal neural tube, the "rhombic lip", contribute the ventral nuclei (i.e., nuclei pontis medialis, lateralis and olivaris inferior), whose functions are essentially associative. This study shows different types of cell migration. Dorsoventral and ventrodorsal movements are essentially active from E5 to E8. In the medulla oblongata, the dorsoventral stream is highly predominant. From E8 to E9, cells belonging to the marginal stream cross the midline laterally in both directions. Beyond E12, longitudinal migrations occur ventrally in both rostrocaudal and caudorostral directions. The immunohistochemical analyses carried out on chimeras generated in experiment V revealed the existence of fibers in marginal zones prior to the onset of the migration of cell bodies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1867386 TI - Transforming growth factor-beta 1 localized within the heart of the chick embryo. AB - Transforming growth factor-beta 1 is a pleiotropic peptide mediator of growth, differentiation, and extracellular matrix synthesis. In the embryonic chick heart prior to the formation of the endocardial cushions, evidence from in vitro experiments suggests that transforming growth factor-beta 1 may be an inducer of the differentiation of atrioventricular endothelial cells into endocardial cushion mesenchyme. Further in vitro evidence suggests that the factor stimulates mesenchymal cell proliferation, and, thus, growth of the cushions. Using an antibody made against a peptide duplicating the aminoterminal 30 amino acid sequence of transforming growth factor-beta 1, we stained sections of stage 11, 18, 23, 26, and 36 chick hearts by an in situ immunofluorescence technique. Transforming growth factor-beta 1 staining localized to the endocardial surface and epicardial surface of the stage 11 heart, but it decreased from these locations in later stages. The cardiac jelly (stage 11), endocardial cushions (stage 18, 23, and 26), and, subsequently, the heart valve leaflets (stage 36) stained intensely for the growth factor. PMID- 1867387 TI - Differentiation of renal intercalated cells in fetal and postnatal rats. AB - An ultrastructural study was conducted on the kidneys from rat fetuses and pups from ages ranging from birth to 8 weeks to identify the time of appearance of each of the two intercalated cell types. With transmission electron microscopy. A intercalated cells were recognized by their large apical microvilli and microplicae as well as by the numerous subapical vesicles. Their identification was confirmed by the presence of typical studs at the cytoplasmic face of the apical plasma membrane. By scanning electron microscopy the cells were recognized by their typical microplicae at the apical surface. In 19-day-old fetuses and newborns. A-intercalated cells were numerous in the epithelium lining the renal pelvis and inner medullary intercalated ducts. Two weeks after birth they disappeared from these regions but became numerous at the outer medullary collecting ducts and also at the cortical collecting ducts although to a lesser degree. B-intercalated cells were recognized by the scarcity of microvilli, the absence of microplicae, and the large number of basal infoldings. Their identification was confirmed by the presence of studs at the cytoplasmic face of the basolateral membrane. B-cells started to appear 3 weeks after birth and increased thereafter. We speculate that the particular stages at which the two cell types differentiate might be related to changes in acid-base status. PMID- 1867388 TI - Distribution and migration of angiogenic cells from grafted avascular intraembryonic mesoderm. AB - The hemangiogenic potencies of initially avascular intra-embryonic mesoderm were studied in chick and quail embryos and in chick-quail chimeras. The prechordal mesoderm, primitive streak and primitive node of quail embryos were heterospecifically grafted into limb buds of chick embryos. Hemangiopoietic quail cells in the host limb were detected by immunohistological staining with the monoclonal anti-MB-1 antibody after 3-6 days of re-incubation. The antibody is specifically directed against quail hemangiopoietic cells and their derivatives. Quail endothelial cells were found in pure quail and in chimeric vessels, inside as well as outside the graft. The main artery of the limb and the vessels inside the graft were connected by chimeric arteries. Proximal to the graft, quail endothelial cells were located predominantly within the lining of the main artery, while distally they were found mainly in the veins and the marginal sinus. The results show that, as early as stage 3 (according to Hamburger and Hamilton 1951, HH) all parts of the avascular intraembryonic mesoderm tested, give rise to endothelial cells. Both mechanisms, angiogenesis and vasculogenesis, contribute to the vascularization of the limb. Immunocytological and scanning electron microscopic studies indicate that centrifugal and centripetal migration of angiogenic cells occurs outside the vessels as well as on the inner surface of the endothelium. PMID- 1867389 TI - A scanning electron microscope study of vascular development in the dental papilla of prenatal rat molars. AB - Prenatal development of the vascular supply to the dental papilla was studied in the maxillary first molar teeth of rats from 18.5 to 22.0 days gestation, using the vascular casting/scanning electron microscope method. Five pulp horns developed in order, central, distal, mesial, disto-lingual and mesio-lingual with the development of the dental papilla. The first vessels that invaded each pulp horn were slightly depressed and formed an irregular network. The newly developed blood vessels were found to grow by sprouting and loop formation. After the invasion, blood vessels at the top of the horn became wider and then diminished in size to form a dense vascular network. The growth of the blood vessels in the latter stages is thought to take place mainly at the tops of the horns, and it is suggested that narrower capillaries arise from wide vessels. A dense and flattened vascular network consisting of thin blood vessels was formed when mesenchymal cells were beginning to differentiate into odontoblasts. The increase in density is thought to correlate with the differentiation of odontoblasts. PMID- 1867391 TI - Distribution and regulation of progesterone receptor in the urogenital tract of the chick embryo. An immunohistochemical study. AB - The early appearance, cellular distribution, and hormonal regulation of the progesterone receptor was studied in the urogenital tract of the chick embryo using antibodies to the receptor molecule. In embryos at day 5 of incubation the receptor is revealed in cell nuclei of the mesenchyme and the coelomic epithelium near the primordium of the urogenital sinus. In embryos at days 6 to 10 immunostained cells are found in the mesenchyme surrounding the urodeal and proctodeal epithelia. The first difference between male and female embryos appears at day 8, with a higher density of progesterone receptor-containing cells along the urogenital sinus epithelium in females. The female type of receptor positive cell distribution can be induced in males by oestradiol treatment. Anti oestrogens applied from day 0 of incubation do not prevent or delay the appearance of PR, but induce a male-type distribution in female embryos. In the gonads, immunostained cells appear unambiguously at day 6 in the medulla. At later stages, the receptor is revealed mostly in the medulla, although there are also positive cells in the cortex of the left ovary. The immunoreactivity is not significantly modified by oestradiol or anti-oestrogens. The mesonephros is devoid of immunoreactivity, whereas most cells of the metanephric mesenchyme are receptor-positive. In the Mullerian ducts progesterone receptor is not detected in control embryos of either sex until after day 10. Between days 6 and 7 Mullerian ducts become responsive to oestradiol, which induces progesterone receptor in luminal epithelial cells. In the spinal cord, receptor is detected in neurones of the ventral horn and the meninges, starting at day 6. The progesterone receptor is up-regulated by oestradiol in the mesenchymal cells. Mullerian ducts, and mesothelium, but not in the gonads or the spinal cord. In none of the tissues or organs where the receptor appears naturally during development could an anti-oestrogen treatment with Tamoxifen or RU39411 block or delay its constitutive appearance. The widespread and specific distribution of the progesterone receptor, its programmed appearance in various organs, and its precise hormonal regulation, are in favour of a morphogenetic role of progesterone in tissue differentiation, related or not to sexual differentiation of the urogenital tract. PMID- 1867393 TI - Rapid determination of cancellous bone mineral loss in ovariectomized rats by a subtraction technique. AB - We present a rapid technique for determining cancellous bone mineral changes in small experimental animals. We used the distal centimeter of the right femur from ovariectomized (OX) (N = 30) and shamovariectomized (ShOX) (N = 28) rats, aged 90 days at surgery and killed at times from 125-540 days postsurgery. We used dual photon absorptiometry to scan the segment three times: intact, after parasagittal splitting, and after removing all cancellous bone. We equated the difference between the second and third scans to cancellous bone mineral content (Cn.BMC). To validate this, we compared it with histomorphometrically determined bone volume (BV/TV) of the proximal tibial metaphysis of the same rat. Parasagittally splitting the segment removed no detectable mineral. OX rats had 40% less Cn.BMC than ShOX rats. However, OX rats had 80% lower BV/TV than ShOX rats. The subtraction technique not only makes a rapid, reasonable assessment of cancellous bone loss in OX rats but permits a smaller sample size than histomorphometry. The histomorphometric technique finds a greater difference between OX and ShOX rats because it examines a region where cancellous bone loss is more marked than does the scanning technique. The current technique measures bone of not only the central secondary spongiosa but also the juxtacortical region and the primary spongiosa, where OX-related differences are less prominent. The principles of this subtraction technique proved workable. However, for the future, we recommend a two-scan technique using a dual energy X-ray scanner. It is likely to take only 20-30 min per specimen to assess cancellous bone mineral. PMID- 1867392 TI - Differential expression of calbindin-D 28 kDa in rat incisor ameloblasts throughout enamel development. AB - Calbindin-D 28 kDa (CaBP 28 kDa), a vitamin D-dependent calcium-binding protein, has been associated with calcium handling by cells. We have investigated the expression of this protein in the rat incisor enamel organ, an epithelium interposed between a mineralizing matrix and connective tissue rich in blood vessels, by radioimmunoassay (RIA), Western blotting, and quantitative protein A gold immunocytochemistry with antibodies to rat kidney CaBP 28 kDa. RIA of cytosolic extracts showed that enamel organs contained relatively high concentrations of CaBP 28 kDa (compared to kidney; see review by Christakos S., C. Gabrielides, and W.B. Rhoten 1989 Endocr. Rev., 10:3-25). Immunoblotting of proteins extracted from enamel organ strips revealed an intensely-stained band near 28 kDa throughout amelogenesis following ameloblast differentiation. Immunocytochemically, CaBP 28 kDa was localized exclusively within ameloblasts. The density of labelling increased from the presecretory stage to the secretory stage and fluctuated across the maturation stage in relation to ameloblast modulation. Ruffle-ended ameloblasts consistently showed the most intense immunoreaction. Gold particles were present throughout the cytoplasm and nuclei of ameloblasts but regions rich in rough endoplasmic reticulum or cell webs showed a higher immunolabelling. Some gold particles were also associated with the external face of the rough endoplasmic reticulum. Multivesicular bodies in maturation stage ameloblasts were occasionally immunoreactive. These data suggest that the intracellular concentration of CaBP 28 kDa is regulated throughout amelogenesis reflecting a stage-specific control of calcium homeostasis in ameloblasts. PMID- 1867390 TI - The role of fibronectin and laminin in development and migration of the avian Wolffian duct with reference to somitogenesis. AB - It has been suggested that matrix molecules like fibronectin and laminin influence the differentiation and migration of embryonic cells. We investigated the role of these two glycoproteins in somitogenesis as well as in the differentiation and migration of the avian Wolffian (pronephric and mesonephric) duct. At first, we described essential steps in the development of these two organ anlagen by light microscopy, SEM and TEM. To localize fibronectin and laminin more exactly in the actual stages, we used the indirect immunoperoxidase reaction at the light microscopic level and the peroxidase-antiperoxidase technique at the ultrastructural level. Fibronectin was found at the surface of the unsegmented paraxial mesoderm, increasing in the cranial direction, and in the basal laminae of somites and Wolffian duct. The mesenchymal tip of the duct contains a moderate amount of fibronectin. In the two investigated organ anlagen, laminin was found mainly in the basal laminae. The role of fibronectin and laminin was investigated further by using synthetic peptides that mimic the main cell binding domain of either fibronectin or laminin, and that competitively inhibit their cell surface receptors. Thus, the pentapeptides GRGDS, YIGSR, and for control, SHLVE were micro-injected under the ectoderm of 2-day-old embryos. After treatment with GRDS, the Wolffian duct and the segmental plate are more compact. The rounded cells exhibit only short processes and narrow intercellular spaces. At the side of injection the duct shows a delay in migration. After treatment with YIGSR the Wolffian duct migrated laterally over the somatopleure. The basal laminae seem to be incomplete. SHLVE had no effect. Our results suggest that fibronectin is a prerequisite for the migration of the Wolffian duct, and that laminin probably plays a role in guiding the duct. The epithelialization during somitogenesis and differentiation of the duct is a more complex process involving also fibronectin and laminin. PMID- 1867394 TI - Fibronectin filaments and actin microfilaments are organized into a fibronexus in Dupuytren's diseased tissue. AB - The fibronexus is a close transmembrane association between fibronectin filaments and actin microfilaments. It has been found at the surfaces of fibroblasts in tissue culture, as well as within contracting granulation tissue. This specialized connection has been proposed to play an important role in the adhesive properties of fibroblasts. The purpose of this study is to determine whether the fibronexus is present in other contracting tissues besides granulation tissue, specifically in Dupuytren's diseased tissue. Dupuytren's disease is a pathologic condition in which the palmar aponeurosis becomes shortened leading to irreversible flexion of the digits. Shortening of the aponeurosis is believed to be an active cellular process. Extracellular filaments and actin microfilaments form close transmembrane associations at the surfaces of actin-rich fibroblasts in Dupuytren's disease. Extracellular filaments extend from the cell surface into the surrounding tissue connecting fibroblasts with collagen fibrils and adjacent cells. In this study we have used immunoelectron microscopy to demonstrate that the extracellular filaments that participate in these close transmembrane associations contain fibronectin. High voltage electron microscopy has been used to examine the three-dimensional relationships between the cytoskeleton and fibronectin filaments in Dupuytren's diseased tissue. We propose that the fibronexus is a dominant adhesive structure at the surface of fibroblasts in Dupuytren's diseased tissue. The fibronexus, by mediating cell-to cell and cell-to-matrix attachments, may serve to transmit contractile forces generated by actin microfilaments in these cells throughout the diseased tissue. PMID- 1867395 TI - Muscle spindle ultrastructure revealed by conventional and high-resolution scanning electron microscopy. AB - Muscle spindles in the tenuissimus muscle of mature golden Syrian hamsters were examined by conventional and high-resolution scanning electron microscopy (HRSEM). For conventional SEM, entire muscles were first fixed in 2.5% buffered glutaraldehyde. Spindles were then isolated with a dissecting microscope under darkfield illumination and postfixed in 1.0% OsO4. Some spindles were treated with 8 N HCl at 60 degrees C to clearly expose intrafusal fiber surfaces once the outer capsular sheath was mechanically disrupted. Preparation for HRSEM included aldehyde/osmium fixation and freeze-cleavage in liquid N2. The cytosol and certain cellular elements were also selectively extracted by immersion in 0.1% OsO4 for varying time intervals. In these preparations, the capsular sleeve showed a multilayered pattern of vesicle-laden cells with variant surface topography in different regions, including filopodia and small bristle-like surface-projections. An interlacing three-dimensional network of collagen fibrils intervened between the capsular lamellae. Within the spindles, sensory and fusimotor nerve endings closely adhered to the outer surfaces of intrafusal fibers. Sensory nerve terminals were enveloped by a prominent external lamina, and those that were cleaved open contained a plethora of elongated mitochondria that ran parallel with the longitudinal axis, along with vesicles, axoplasmic filaments, and lysosomes. Multiple adhesion sites between the sensory nerve membrane and the underlying sarcolemma of the intrafusal fiber were also observed in select regions. Fusimotor nerve endings were covered externally by processes of Schwann cells and their axoplasm was filled with a multitude of cellular organelles and synaptic vesicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867396 TI - Effect of tunicamycin, an inhibitor of protein glycosylation, on testicular cord organization in fetal mouse gonadal explants in vitro. AB - The effect of tunicamycin (TM) on testicular cord organization in the fetal mouse was examined in vitro at light and electron microscopic levels, with special reference to the glycoprotein functions during Sertoli cell differentiation. In testicular explants treated with TM, testicular cord organization was inhibited. TM treatment affected basal lamina formation by Sertoli cells, resulting in a discontinuous basal lamina or none at all in certain areas. The disorganized Sertoli cells were amorphous in shape, exhibited poor epithelial polarity, and were irregularly arranged in the testicular parenchyma. Extracellular matrix and collagen fibers were often observed in the intercellular spaces between the disorganized Sertoli cells. Lectin histochemical observation revealed that the number of wheat germ agglutinin binding sites on the plasma membrane and basal lamina of disorganized Sertoli cells was significantly decreased by TM treatment. However, junctions were normally observed in the plasma membrane between disorganized Sertoli cells. Leydig cells showed a normal differentiation in the testicular parenchyma in the presence of TM. These observations suggest that basal lamina formation of Sertoli cells and/or the expression of their cell surface glycoconjugates may be crucial for the establishment of Sertoli cell polarity and/or the Sertoli-Sertoli cell interactions required for proper testicular cord formation. Sertoli cell organization into testicular cords and Leydig cell differentiation may be controlled by different regulatory mechanisms. PMID- 1867397 TI - Changes in actin distribution during sperm development in the opossum, Monodelphis domestica. AB - The distribution of actin in spermatogenic cells and epididymal spermatozoa of the opossum, Monodelphis domestica, was examined by immunofluorescence microscopy to identify its potential function in the major structural events of sperm development. In spermatogenic cells actin was located at the site of initial interaction between the nucleus and acrosome and remained present through subsequent acrosome morphogenesis. Actin was also associated both with the posterior pole of the nucleus, at the site of flagellar attachment, and with the manchette. Thus actin may play a role in establishing the specific associations of spermatid organelles and in the streamlining of the cells' architecture. In epididymal spermatozoa two sites of actin localization are present. The first site is surrounding the connecting piece where it may participate in the characteristic 90 degrees rotation of the head. The second site was a ring of actin surrounding the lateral boundary of the acrosome where it may play a role in the sperm pairing process which also occurs in the epididymis. PMID- 1867398 TI - Development of esophageal epithelium in the fetal and neonatal mouse. AB - Development of the fetal mouse esophageal epithelium was followed using light microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and radioautography. At 15 days of gestation in the cervical (C), mediastinal (M), and abdominal (A) segments of the esophagus, the epithelium was two or three cells thick, and only cells located in the basal (germinal) layer incorporated tritiated thymidine. Ciliated cells were sparse in all three segments. At 17 days of gestation, longitudinal mesenchymal ridges became more differentiated in the distal segment. Labeling indices were lower than at preceding stages in each segment. Ciliated cells had increased in number and appeared to be evenly distributed along the whole esophagus. In periodic acid Schiff (PAS)-stained sections, an increasing proximodistal distribution of glycogen stores was observed, with greatest concentrations found in segment A. At 18 days of gestation, labeling indices were comparable in segments C and M (11.7% +/- 2.9% and 12.8% +/- 1.9%, respectively) but remained higher in segment A (17.9% +/- 2.0%). Ciliated cells were still present. At this stage, transverse circular furrows and ridges started to appear. They increased in number at 4 days after birth and were very closely distributed in the adult. In longitudinal sections, these ridges corresponded to projections of stratum granulosum and of the overlying stratum corneum. After birth, ciliated cells desquamated rapidly but some patches were still present at 4 days. At 8 days, the esophageal epithelium was not yet keratinized. PMID- 1867399 TI - Colloidal gold localization of type IV collagen in the extracellular matrix of rat gastric mucosa: influence of alcohol and prostaglandin. AB - The effect of acute alcohol exposure on the gastric mucosal basal lamina, and its major structural protein type IV collagen, was assessed by transmission electron microscopy (TEM) and immunogold (IG) labeling of this collagenous material. Fasted rats orally received either 50% or 100% ethanol. Five or 60 minutes later animals were sacrificed and mucosal samples were obtained from the glandular epithelium for TEM or IG localization of type IV collagen. For IG studies, the number of gold particles/area lamina densa was quantified in interfoveolar, pit, and gland regions as an index of the molecular integrity of type IV collagen. Both ethanol concentrations induced epithelial exfoliation with pleating of the denuded lamina densa. Absolute ethanol, and to a lesser extent 50% ethanol, caused frequent rupture of a thickened, precipitated lamina densa. Immunolabeling of type IV collagen varied with the experimental protocol. In control tissues exposed to oral saline, binding was greatest in the interfoveolar zone. Low binding occurred with 100% ethanol in all regions when compared with controls, but 50% ethanol evoked significantly higher binding in interfoveolar regions, in a similar fashion to controls. In additional studies in which 16,16 dimethyl prostaglandin E2 (PGE2) (10 micrograms/kg) was injected subcutaneously prior to oral ethanol exposure, PGE2 pretreatment prevented the large decrease in IG binding induced by absolute ethanol, but the level still remained significantly less than with corresponding controls. In contrast, pretreatment with PGE2 prior to 50% ethanol exposure restored type IV collagen immunolabeling to control levels. These results indicate that ethanol induces a concentration-dependent lowering of IG binding to type IV collagen which also effects its reversibility by PGE2. PMID- 1867400 TI - Immunohistochemical comparison of T-cell and macrophage populations in mammary tissue of control and Trichinella spiralis-infected rats. AB - We have shown that antigen-specific T lymphocytes can mediate maternal-to neonatal immunity during lactation. Present studies address the dynamics of lymphocyte accumulation in the mammary gland during normal and disease stimulated conditions. Monoclonal antibodies specific for total T cells, suppressor/cytotoxic and helper subsets, and macrophages were used in conjunction with immunohistochemistry to identify and count the individual cell types. In unstimulated mammary tissue, following a rise in T cells to maximal numbers in late pregnancy, the total number of T cells/high power field (HPF) was significantly diminished in early lactation and continued to decline to the late lactation period. Both the numbers of T cells/HPF located in the mammary alveolar epithelium and surrounding connective tissue were significantly reduced in early lactation as compared to late pregnancy. This indicates the possible passage of cells into the milk during lactation. Prior infection of the mother with Trichinella spiralis and a secondary challenge 48 h. before sacrifice caused a significant reduction in the number of T cells in the mammary tissue in early lactation as compared with unstimulated controls, indicating the possibility of an even greater outflow of T cells into milk. In controls, the T suppressor/cytotoxic subtype showed a reduction in early lactation versus late pregnancy but showed no shifts in total cells/HPF during infection. The T-helper subtype in controls remained unchanged from late pregnancy to early lactation with a considerable decline in late lactation. However, the T-helper cells were significantly decreased in T. spiralis-treated animals as compared with noninfected controls in early lactation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867401 TI - Freeze-fracture observations on human fetal kidney in serum-free organ culture. AB - The current study was undertaken to examine and characterize junctional complexes, through freeze-fracture, in developing human fetal kidney and in cultured renal explants maturing in vitro. Tissue specimens were cultured for 7 days in Leibovitz's L-15 medium in the absence of serum or hormones. In uncultured explants, cells in the different nephron segments were joined by zonulae occludentes which consisted of ridges on the P-face and grooves on the E face of lateral membranes. Tight junction composition was heterogeneous and complexity increased from proximal to collecting tubules. Proximal tubule cells were also characterized by the presence of gap junctions and a brush border. Podocytes were joined by macular junctions, while zipper-like junctions were observed between collecting duct cells. Intercalated cells were decorated with rod-shaped intramembrane particles on lateral and apical membranes, instead of the usual spherical particles present in other cells. All these structures could be observed at various intervals during tissue culture, indicating the preservation of ultrastructural integrity of the explants. These observations extend and support previous studies made at the light and electron microscopic levels. Thence, the present culture model constitutes a valuable tool to study the direct effect of growth factors on nephrogenesis. PMID- 1867402 TI - Prenatal and postnatal development of the large intestine in the insectivore Suncus murinus, the laboratory shrew. AB - Development of the large intestine in the insectivore Suncus murinus (the laboratory shrew) was investigated from day 21 to 30 of gestation and from birth to 20 days of age. Two days before birth, the stratified epithelium in the large intestine changed into a single layer. Although neither villi nor villus-like structures were ever present, fissures, corresponding to openings of the crypts, appeared on the mucosal surface before birth. These increased in number as well as in width and depth, connected with each other, and gave the mucosal surface a ridge-like appearance by 20 days of age. An elevation containing submucosae appeared shortly after birth and formed a large circular fold during the neonatal period. Goblet cells were the predominant epithelial cell type. Individual epithelial cells were mature-looking a few days before birth; goblet cells contained numerous mucous globules and absorptive cells possessed well-developed organelles. However, although goblet cells increased in number and exhibited active mucous-releasing forms after birth, absorptive cells never showed morphologic evidence of active endocytosis, such as apical endocytotic complexes and large supranuclear vacuoles. Each epithelial cell was similar in ultrastructure to that of the adult shortly after birth. PMID- 1867403 TI - Effects of maternal bilateral ureteral ligation on the differentiation of glomerular anionic sites in fetal rat kidney. AB - Effects of maternal bilateral ureteral ligation on the differentiation of glomerular anionic sites in fetal kidney were studied with the colloidal iron method. The ligation was performed on days 17, 19, and 21 of pregnancy, and the animal were euthanized 1 day after each ligation. On fetal day 20, in the fetuses from ligated mothers, colloidal iron was concentrated in laminae rarae interna and externa of the glomerular basement membrane. In the fetuses from sham-ligated mothers, however, a different pattern of iron distribution was noted. In most areas of the glomerular basement membrane, colloidal iron was randomly distributed as in both fetuses of fetal day 18. In the remaining areas, the same pattern of colloidal iron distribution as was noted in the fetuses from ligated mothers of fetal day 20 was observed. On fetal day 22, colloidal iron was densely accumulated in laminae rarae interna and externa of the glomerular basement membrane in both groups. However, the iron-free zone was slightly thicker in the fetuses from the ligated mothers. These findings suggest that maternal bilateral ureteral ligation accelerates the differentiation of glomerular anionic sites in the kidney of fetal rats. PMID- 1867404 TI - Characteristics of end-plates formed in mouse skeletal muscles reinnervated by their own or by foreign nerves. AB - Morphological and electrophysiological techniques were used to study the neuromuscular junctions of soleus and extensor digitorum longus muscles in normal mice and 6 months after reinnervation by either their original or foreign nerves. In muscles reinnervated by foreign nerves, there were increased incidences of morphological abnormalities, including ultra-terminal axonal sprouting, multiaxonal innervation of end-plates, and ectopic synapse formation, as compared with both normal muscles and muscles reinnervated by their correct nerves. In spite of the morphological abnormalities, however, there was no evidence that the effectiveness of synapses (as estimated from the mean quantal content, m, of end plate potentials) formed between nerves and inappropriate muscles was impaired. As had also been found in normally innervated muscles, the value of m was again higher in extensor digitorum longus than in soleus following reinnervation by inappropriate nerves. These results suggest that in mammals, when muscles are reinnervated by foreign nerves, mechanisms exist to maintain the efficacy of neuromuscular transmission, in contrast to the situation in amphibians (Sayers and Tonge, 1982: J. Physiol. (Lond.), 330:57-68). The abnormalities observed in this study following reinnervation may be a morphological manifestation of these corrective mechanisms. PMID- 1867405 TI - The restraining function of the cruciate ligaments on hyperextension and hyperflexion of the human knee joint. AB - Each of the cruciate ligaments contains functionally different fiber groups; one fiber bundle is always taut; numerous others are taut in intermediate or extreme positions. The bulk of the fibers of the anterior cruciate ligament (ACL) is taut in maximal extension, while that of the posterior cruciate ligament (PCL) is taut in the intermediate positions and in maximal flexion. Fibers taut in extreme positions serve as restraints: during hyperextension, the ACL restrains forward migration of its tibial attachment, while the PCL interacts with other structures to prevent posterior opening of the joint. The inverse situation occurs in hyperflexion. Cruciate fibers are dissimilar in length and angular arrangement so that, when movements are restrained, they lengthen to different extents. To define this phenomenon in quantitative terms, the term isokolyons was coined for lines from which fibers showing identical elongation in percentage on exposure to a force take their origin. PMID- 1867407 TI - Influence of age on nuclear bodies and nuclear volume in pituicytes of the rat neurohypophysis. AB - This study has analyzed age-related changes in the nuclear organization of pituicytes of the rat. The cytological study of the cell nucleus and the quantitative analysis of nuclear bodies (NBs) were performed on ultrathin sections. Nuclear diameter, perimeter, and area were measured on semithin sections, and nuclear volume was estimated from these data. The nucleolus was mainly composed of a few large fibrillar centers with their associated dense fibrillar component, whereas the granular component tended to form large masses at the nucleolar periphery. The most frequent configuration of NBs was a globular inclusion composed of a fibrillar capsule with a core that contained a few electron-dense granules. Intranuclear glycogen was detected on rare occasions and only in old rats. The proportion of nuclear sections containing NBs increased significantly from 1.5% in 3-month-old rats to 8.6% in 18-month-old rats. A significant increase in the nuclear volume was detected in older rats with respect to the younger ones (157 +/- 69 vs. 98 +/- 43 microns 3, mean +/- S.D.). Our results suggest an age-related activation of nuclear metabolism in pituicytes resulting in a nuclear expansion and an increase in the frequency of appearance of NBs. This activation might be a reactive cellular event induced by the degenerative changes in neurosecretory nerve endings naturally occurring in older animals. PMID- 1867406 TI - Heterogeneity among ovarian blood vessels: endogenous hepatic lipase is concentrated in blood vessels of rat corpora lutea. AB - We used indirect immunofluorescence and immunogold light microscopy to examine the distribution of hepatic lipase, an enzyme involved in lipoprotein metabolism, in ovaries of gonadotropin-treated immature rats. Antibodies utilized were rabbit anti-rat hepatic lipase IgG, anti-rat von Willebrand factor (VWF, an endothelial cell marker), and goat anti-rabbit IgG conjugated to gold particles or rhodamine. Immunoreagents were applied to fresh frozen sections of unfixed ovary or liver (positive control) or were delivered to ovaries by vascular perfusion before fixation in situ and silver-enhancement of sections. Appropriate controls verified that the immunolocalizations were specific. Immunofluorescence implied that luteal but not stromal blood vessels of ovaries were positive for hepatic lipase, whereas luteal and stromal blood vessels bore VWF. The improved morphology gained by perfusing ovaries with antibodies allowed precise localization of the enzyme. Hepatic lipase was concentrated within thin-walled vessels of corpora lutea but not those of stroma in ovaries at the time of peak steroidogenic activity. Quantification of hepatic lipase-labeled vessels in stromal and luteal compartments confirmed our visual impression. Many images suggested that stromal vessels lacking hepatic lipase gained this enzyme upon contact with luteal tissue. Perfusion of ovaries with cationized ferritin labeled all ovarian vessels equally well, ruling out the possibility that the observed distribution of hepatic lipase was artifactual. These findings demonstrate that ovarian blood vessels are heterogeneous for hepatic lipase. Moreover, they imply that luteal tissue, perhaps luteal cells, may influence expression of hepatic lipase binding sites by endothelial cells. PMID- 1867408 TI - Adaptation of diaphyseal structure with aging and increased mechanical usage in the adult rat: a histomorphometrical and biomechanical study. AB - The experimental increase in mechanical usage or overloading of the left hindlimb was produced by immobilization of the contralateral hindlimb. The right hindlimb was placed in a flexed position against the body and was immobilized using an elastic bandage. Some control animals were sacrificed initially at time zero and increased mechanical usage and age-matched control animals were sacrificed after 2, 10, 18, and 26 weeks of treatment. All animals received double bone fluorochrome labeling prior to sacrifice. Cortical bone histomorphometry and cross-sectional moments of inertia were determined. Marrow cavity enlargement and total cross-sectional area expansion represented the age-related cortical bone changes. Increased mechanical usage enhanced periosteal bone modeling in the formation mode and dampened endocortical bone remodeling and bone modeling in the resorption mode (resorption drift) to create a slight positive bone balance. These observations are in general agreement with Frost's postulate for mechanical effects on bone modeling and remodeling (Frost, H.M. 1987b. Bone "mass" and the "mechanostat." A proposal. Anat. Rec. 219: 1-9). The maximum moment of inertia did not change significantly in either control or overloaded tibial shafts. The minimum and polar moment of inertias in overloaded bones increases over those of controls at 18 and 26 weeks of the experiment. PMID- 1867409 TI - Changes of glycoconjugate contents of the zona pellucida during oocyte growth and development in the golden hamster: a quantitative cytochemical study. AB - We demonstrated here with the high resolution lectin-gold approach and quantitative analysis, changes of glycoconjugates in the hamster zona pellucida (ZP) during oocyte growth and development in the ovary and the oviduct. Glycoconjugates which contain N-acetyl-D-galactosamine as terminal sugar residues are absent in the ovary but are secreted by secretory cells in the oviduct and are added to the ZP of superovulated oocytes during oviductal transit. Glycoconjugates which carry sialic acid as terminal sugar residues appear to be acquired mainly from the ovary. The oviduct contributes little of this particular component to the ZP during the transit of oocytes in the oviduct. On the contrary D-galactose and N-acetylglucosamine associated glycoconjugates, added to the ZP in ovarian follicles, are also secreted by non-ciliated oviductal epithelial cells and these secretory products are transferred to the ZP in significant amount during passage of the oocyte through the oviduct. Lectin-gold labeling of the ZP of superovulated oocytes reveals homogeneous distribution of gold particles throughout the zona matrix. Thus, we conclude that the ZP of hamster superovulated oocytes consists of glycoconjugates that may derive from different origins. Deposition of ZP glycocomponents begins in the ovary. Similar and new glycoconjugates, secreted by oviductal non-ciliated secretory cells, are added to the ZP of oocytes during oviductal transit. At this stage the ZP is made up of a homogeneous matrix of glycoconjugates. PMID- 1867411 TI - The structural organization and adrenergic innervation of the carotid arterial system of the giraffe (Giraffa camelopardalis). AB - The sympathetic innervation of the giraffe (Giraffa camelopardalis) carotid arterial system is described in this study using the sucrose-potassium phosphate glyoxylic acid (SPG) method. The brachiocephalic and bicarotid trunks showed a paucity of sympathetic innervation. Smooth muscle nests observed in the outer layers of the tunica media in these arteries revealed a rich network of sympathetic nerve fibres. The common carotid artery showed numerous sympathetic nerve fibres particularly in the outer muscular zone of the tunica media. The internal maxillary, ramus anastomoticus, and arteria anastomotica also revealed a rich sympathetic innervation and a deep penetration of the nerve fibres into the tunica media. It is suggested that the rich sympathetic innervation of the giraffe carotid arteries maintains a basal tonic state in the smooth muscle in the tunica media. This, in turn, may enable the animal to maintain a relatively high rate of blood flow in the carotid arteries in diastole despite the pressure run-off. It is further suggested that the muscular structure and dense sympathetic innervation of the internal maxillary and its branches to the carotid rete mirabile provide the animal with an array of mechanisms to modulate its cranial circulation particularly when it bends its head to drink. PMID- 1867410 TI - Correlation between blood-testis barrier development and onset of the first spermatogenic wave in normal and in busulfan-treated rats: a lanthanum and freeze fracture study. AB - Pregnant rats (day 13) received 10 mg/kg of Busulfan i.p. The seminiferous tubules of their offspring from post-natal age 1 day up to day 35 were examined with TEM after fixation plus intercellular tracers, and with freeze-fracture techniques. During this period, the inter-Sertoli tight junctions of controls increase both in number and in length. Between days 10 and 13 the seminiferous cords have numerous preleptotene and leptotene spermatocytes surrounded by tracer. The inter-Sertoli junctions are tortuous and predominantly perpendicular to the basal lamina. Between ages 13 and 20 days the seminiferous epithelium reaches zygotene-pachytene stages. The tracer is stopped at the inter-Sertoli junctions at this stage, whereas it still permeates tubules displaying preleptotene and leptotene spermatocytes. Freeze-fracture shows that the orientation of inter-Sertoli junctions has changed to parallel, both to each other and to the basal lamina. In the Busulfan-treated rats, the tubules continue having, up to post-natal day 30, only Sertoli cells and scanty spermatogonia. In these, lanthanum penetration goes as far as the apical Sertoli cell region; the inter-Sertoli junctions still show tortuous strands, and most are oriented perpendicular to the basal lamina. This indicates that formation of the first competent inter-Sertoli junctions is temporo-spatially simultaneous with the appearance of zygotene-pachytene spermatocytes. PMID- 1867412 TI - A fine morphological study of germ cells in asymmetrically developing right and left ovaries of the chick. AB - Germ cells of the chick ovary which develop asymmetrically on the right and left sides of the embryo were observed by electron microscopy from 7 to 17 days of incubation. Germ cells showed different patterns in the right and left ovaries, and also differences in the cortex and in the medulla. At 7 to 9 days, germ cells were individually present in both the right and left ovaries. They proliferated from 10 days onward and formed many cell aggregates. In each aggregate, germ cells were joined by intercellular bridges, and their cell cycles were synchronized. Although meiotic features of the germ cells were frequently found in the cortex of the left ovaries at 16 days, some germ cells exhibited these features at earlier days. In the meiotic germ cells, the "Balbiani body," which was composed of a concentration of cell organelles shifted to one pole of the cell, was always seen. The appearance of a meiotic nucleus and Balbiani body was characteristic of germ cells located in the left ovarian cortex, whereas those were never seen in the left medulla and in the right ovary. At 16 and 17 days, some germ cells were released into the lacunae of the medulla of both the right and left ovaries. The meaning of this phenomenon is discussed. Degenerating germ cells were frequently observed in the right ovary, but rarely in the left. PMID- 1867413 TI - Extracellular matrix of the developing heart in normal and cardiac lethal mutant axolotls, Ambystoma mexicanum. AB - As part of an ongoing study of heart development in normal and cardiac lethal mutant axolotls (Mexican salamanders) we examined the extracellular matrix (ECM) by microscopical methods. With scanning electron microscopy we are unable to detect ECM on the apical surface of cells of the early cardiogenic mesoderm. During the period of lateral plate migration, which coincides with the period of cardiogenic induction of mesoderm by anterior endoderm, there is little ECM, aside from some microfibrils, on the basal surface of the endoderm or mesoderm of the pharyngeal region. Later, a basal lamina (BL) is found on the endoderm and along portions of the developing endocardial and myocardial tubes. By the time of heartbeat initiation the BLs are complete and invested with striated collagen like fibrils that are sparsely distributed in the "cardiac jelly" of normal and mutant hearts. Striated fibril deposition, which increases with time, is generally random in orientation, with the exception of some regions where there is a preferred directionality. During the post-hatching period striated fibrils appear in the subepicardial space. In addition, branching fibers that are probably elastin appear in the bulbus arteriosus. In these later stages the density of fibrils in the cardiac lethal mutant heart is much less than normal. Indirect immunofluorescent microscopy reveals laminin and fibronectin in the basal laminae of the endocardial and myocardial tubes of both normal and cardiac lethal mutant hearts. In addition, punctate and fibrillar staining for fibronectin, and punctate staining for laminin are found in the cardiac jelly. These matrix proteins are not abundant at the apical (exterior) surface of the myocardium until the epicardium appears.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867414 TI - Biomechanical changes in the rabbit masticatory system during postnatal development. AB - Using dissection, biometry, and two three-dimensional mechanical models, the postnatal changes of the rabbit masticatory muscles were studied by analyzing their three-dimensional orientation, their strength and fiber lengths, and certain functional consequences of these changes. The first mechanical model uses length-tension relationships of the muscles and predicts the maximum bite force as a function of mandibular position. It shows that young rabbits are able to generate large bite forces at a wider gape than adult animals and that the forces are directed more vertically. In spite of the postnatal changes the mechanical advantage of the system remains about equal. However, the muscles are reoriented so that they exert a larger degree of parallel action, suggesting a larger bite force magnitude but a smaller range of bite force directions. The second model predicts this range. It shows that during postnatal development a relative gain occurs in the possibilities for the system to exert forces directed rostrodorsally. In all other directions the capability to exert force decreases. The results suggest that during development the possibility of the system to generate large bite forces is increased at the cost of a restriction in the range of jaw excursion and that a restriction takes place in the range of possible force directions that can be exerted at the molars. PMID- 1867415 TI - Equine myenteric plexus with special reference to the pelvic flexure pacemaker. AB - Sellers et al. (1979, Am. J. Phys., 237: E457-E464) proposed a pelvic flexure pacemaker mechanism to account for the bidirectional contraction waves needed to both retain ingesta within the right ventral colon for cellulose digestion and terminal fermentation and to transport the digesta distad once the process has been completed. To corroborate the presence of a pelvic flexure pacemaker, we prepared whole mount samples of the tunica muscularis from 23 horses at ten sites along the large colon, cecum and jejunum. Following smooth muscle enzymatic digestion, somata of the myenteric plexus were stained with an RNA-specific agent, Cuprolinic blue. These somata were quantified at each site to establish any regional variations in neuronal density. Results indicated an increased neuronal density at the level of the pelvic flexure, especially in the region of the left dorsal colon. The increased neuronal density at the left dorsal colon compared to the other sampling sites was statistically significant (Wilcoxon signed rank test, P less than .01 at each sampling site). There was remarkable size variation (from 10-60 microns) among neurons at the individual sampling sites. However, no statistically significant size discrepancy existed between sampling sites (Friedman's rank test, P = .10). The 23 horses ranged from 6 months to 15 years of age. No age-related differences in neuronal density was discovered (Kruskal-Wallis ANOVA test, P greater than .05). Neuronal densities did not vary on the basis of sex (Wilcoxon signed pairs test, P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867416 TI - Endocytotic activity of the free floating cells and epithelial cells in the endolymphatic sac: an electron microscopic study. AB - The fine structure and its functional properties of both free floating cells and epithelial cells in the endolymphatic sac after injections of India ink particles or polystyrene latex beads, 0.24 micron in diameter, into the endolymphatic space, were studied using light and electron microscopy. Twenty-four to 48 hours after injections, these foreign materials had accumulated in the lumen of the endolymphatic sac and a large number of them were ingested into free floating cells, most of which appear to be macrophages. Granular leucocytes taking up the foreign materials into the cytoplasm were also recognized in the sac lumen. A few of these leucocytes passed through the epithelium and migrated to the subepithelial connective tissue, while the others were degenerated and phagocytosed by the free floating cells in the lumen of the sac. In addition to the free floating cells, ink particles, latex beads, and degenerated leucocytes were endocytosed into some of the epithelial cells. As we reported previously, the epithelial cells were clearly classified into two types; type-1 epithelial cells (cytoorganelle-rich cells) and type-2 epithelial cells (filament-rich cells). The foreign materials and degenerated cells were taken up mainly into the type-1 epithelial cells, while the type-2 epithelial cells did not show so marked endocytotic activity in comparison with the type-1 epithelial cells. Thus, it becomes clear that the endolymphatic sac plays an important role in the endocytotic activity for foreign materials and waste products, and both the free floating cells and the type-1 epithelial cells of the sac have strong endocytotic activity. PMID- 1867417 TI - Psychomotor performance after desflurane anesthesia: a comparison with isoflurane. AB - Recovery and psychomotor performance were studied in 80 ASA physical status I-III adult patients undergoing outpatient surgery. Patients were divided into four equal groups: thiopental induction of anesthesia followed by desflurane in nitrous oxide and oxygen (Th-DES-N2O/O2), thiopental induction of anesthesia followed by isoflurane in nitrous oxide and oxygen (Th-ISO-N2O/O2), thiopental induction of anesthesia followed by desflurane in oxygen (Th-DES-O2), and desflurane inhaled induction followed by desflurane in oxygen (DES-DES-O2). Patients were excluded from analysis if they required opioids or antiemetics postoperatively. The use of desflurane was associated with more rapid awakening compared with isoflurane (time to eye opening 9.45 +/- 0.67 min [Th-DES-N2O/O2] and 13.8 +/- 1.59 min [Th-ISO-N2O/O2], P less than 0.05). Psychomotor performance was measured using the choice reaction time and critical flicker fusion threshold. At 30 min after discontinuing anesthesia, five patients in the Th-ISO N2O/O2 group and one patient in the Th-DES-N2O/O2 group were too sleepy to perform psychomotor tests. In addition, five patients who received Th-DES-O2 and one patient who received the inhaled induction and maintenance of anesthesia with desflurane in oxygen were too sleepy to perform tests at 30 min. Patients receiving Th-DES-N2O/O2 showed less impairment of choice reaction time than those receiving Th-ISO-N2O/O2. Critical flicker fusion threshold, however, showed no difference between groups. The use of thiopental was associated with delayed recovery. Compared with isoflurane, desflurane anesthesia is associated with more rapid initial awakening and less impairment of choice reaction time. PMID- 1867418 TI - Emergence airway complications in children: a comparison of tracheal extubation in awake and deeply anesthetized patients. AB - We compared the differences in oxygen saturation and airway-related complications after tracheal extubation in pediatric patients undergoing elective strabismus surgery or adenoidectomy and/or tonsillectomy who were awake versus anesthetized. Seventy otherwise healthy patients between 2 and 8 yr of age were studied. Anesthesia was induced with halothane or thiamylal and maintained with nitrous oxide and halothane. After induction of anesthesia, the patients were randomly assigned to group 1 (awake extubation) or group 2 (anesthetized extubation). Oxygen saturation was measured continuously and recorded 10 min before extubation and at 1, 2, 3, 5, 7, 10, 15, 20, 25, and 30 min after tracheal extubation. Supplemental oxygen was administered when oxygen saturation values were less than 90% while breathing room air. Oxygen saturation levels were higher in group 2 than in group 1 at 1, 2, 3, and 5 min after extubation. There were no differences between the two groups in the number of patients requiring supplemental oxygen. The incidence of airway-related complications such as laryngospasm, croup, sore throat, excessive coughing, and arrhythmias was not different between the two groups. We conclude that the anesthesiologist's preference or surgical requirements may dictate the choice of extubation technique in otherwise healthy children undergoing elective surgery. PMID- 1867419 TI - Is premedication with oral glycopyrrolate as effective as oral atropine in attenuating cardiovascular depression in infants receiving halothane for induction of anesthesia? AB - The authors conducted a double-blind study to compare premedication with oral glycopyrrolate and oral atropine in prevention of bradycardia and hypotension during induction of anesthesia with halothane-N2O in 90 outpatient infants and children aged 1-18 mo who were randomized into three groups to receive either an oral placebo, oral atropine (0.02 mg/kg), or oral glycopyrrolate (0.05 mg/kg) approximately 1 h before induction of anesthesia. Heart rate and mean arterial pressure were measured before drug administration, just before induction of anesthesia, and every minute until surgical stimulation occurred. Glycopyrrolate, at the dose used, was significantly less effective than atropine in attenuating bradycardia during induction; neither glycopyrrolate nor atropine altered the incidence or degree of hypotension. Antisialagogic activity and side effects were comparable, except for significantly more flushing with atropine. PMID- 1867420 TI - Neuromuscular effects of succinylcholine on the vocal cords and adductor pollicis muscles. AB - To quantify the effects of succinylcholine at the laryngeal adductor muscles and the adductor pollicis, 17 adult patients were studied during propofol-fentanyl anesthesia. Train-of-four stimulation was applied to the ulnar nerve at the wrist and the recurrent laryngeal nerve at the notch of the thyroid cartilage. Laryngeal response was measured as pressure changes in the cuff of the tracheal tube positioned between the vocal cords. The force of contraction of the laryngeal adductor muscles and of the adductor pollicis were compared after administration of 0.25 or 0.5 mg/kg of succinylcholine. With 0.25 mg/kg, maximum blockade of first twitch (T1) was 66% +/- 10% (mean +/- SEM) and 45% +/- 13% at the vocal cords and the adductor pollicis, respectively (P less than 0.01). After 0.5 mg/kg, maximum blockade at the vocal cords (93% +/- 2%) and the adductor pollicis (84% +/- 6%) did not differ significantly. For both doses, time to maximal blockade was shorter for the vocal cords (0.9 +/- 0.1 min) than for the adductor pollicis (1.7 +/- 0.2 min; P less than 0.01). Time to 90% recovery of T1 after a bolus of 0.5 mg/kg was similar at the vocal cords (4.3 +/- 0.5 min) and the adductor pollicis (5.2 +/- 0.8 min) (NS). The ED50 was less at the laryngeal adductors (0.170 mg/kg) than at the adductor pollicis (0.278 mg/kg). It is concluded that, in adults, succinylcholine-induced blockade is more rapid and more intense at the laryngeal muscles than at the adductor pollicis. PMID- 1867421 TI - Myocardial oxygen supply/demand relations during phenylephrine infusions in dogs. AB - Experiments were performed on 14 fentanyl-pentobarbital-anesthetized dogs to assess changes in myocardial oxygen supply/demand relations during intravenous infusions of phenylephrine (2.8 micrograms.kg-1.min-1). Myocardial blood flow was measured with radioactive microspheres. Myocardial oxygen and lactate extraction were determined. Myocardial oxygen consumption was calculated with the Fick equation. In series 1, measurements were obtained during phenylephrine-induced pressor responses. In series 2, measurements were obtained with aortic pressure maintained constant with an extracorporeal reservoir during phenylephrine infusion, so that coronary vasomotor responses could be assessed in the absence of increases in ventricular afterload and perfusion pressure. In series 1, the phenylephrine-induced increase in mean aortic pressure (+42%) was accompanied by proportional (60%) increases in myocardial blood flow and myocardial oxygen consumption and with no change in the endocardium-to-epicardium flow ratio, oxygen extraction, coronary sinus oxygen tension and oxygen saturation, or myocardial lactate extraction. In series 2, phenylephrine infusion caused a transmurally uniform 15% decrease in myocardial blood flow combined with a 10% decrease in myocardial oxygen consumption. The coronary arteriovenous oxygen difference increased modestly (+5%), resulting in small decreases in coronary sinus oxygen tension and oxygen saturation, whereas lactate extraction was unaffected. The present findings suggest that phenylephrine has a direct vasoconstrictor effect in the coronary circulation that is weak and completely overridden by metabolic autoregulatory mechanisms in response to pressure-induced augmentations in cardiac workload. The authors conclude that the myocardium is not at risk when phenylephrine is used to treat hypotension in patients with adequate cardiac function and coronary vasodilator reserve. PMID- 1867422 TI - Is dantrolene safe to administer in sepsis? The effect of dantrolene after endotoxin administration in dogs and rats. AB - Hyperthermia from septic shock may be indistinguishable from malignant hyperthermia. Dantrolene may be given in septicemia if the diagnosis is unclear. To determine if dantrolene is safe to use in sepsis, two studies were performed. In study 1, 18 anesthetized dogs in which profound septic shock was induced with 5 mg/kg of intravenous Escherichia coli endotoxin were randomized to receive (30 min later) intravenous injections of 10 mg/kg of dantrolene solution, the diluent of dantrolene, or maintenance intravenous fluids alone. The use of dantrolene solution and the diluent of dantrolene resulted in similar but transient statistically significant increases in the cardiac filling pressures and cardiac outputs and decreases in the vascular resistances compared with the control dogs. In a second study, 185 rats were randomized into five equal groups. Groups 1, 2, and 3 received 15 mg/kg of intraperitoneal Escherichia coli endotoxin followed 30 min later by 10 mg/kg of dantrolene solution, the diluent of dantrolene, or normal saline. Groups 4 and 5 received normal saline followed by dantrolene or normal saline. The survival of groups 1, 2, and 3 was less at 24 h (P less than 0.0001) than that of either control group, but was not significantly different from one another. The results suggest dantrolene can be administered safely under clinical conditions where the cause of hyperthermia and shock cannot clearly be ascribed to malignant hyperthermia or septicemia. PMID- 1867423 TI - Subanesthetic concentrations of volatile anesthetics may enhance acquired avoidance training in ddN mice. AB - The effects of halothane, enflurane, and isoflurane on avoidance training were assessed in male ddN mice. Animals were trained to escape an aversive unconditioned stimulus (electric foot shock) within 3 s after being exposed to a conditioned stimulus (light and buzzer). Immediately after training (first session), the animals were exposed to halothane, enflurane, or isoflurane for 120 min and were then tested again on the avoidance task (second session) 30 min after cessation of the exposure. The performance ratios [B/A] (i.e., A is the score in the first session, and B the score in the second) were compared between the anesthetic groups and their respective control groups. Performance ratios in the control animals ([B/A]c) did not reach 100% except for those corresponding to the 0.5 and 1.0 MAC (minimal alveolar anesthetic concentration) halothane groups. Four of the nine performance ratios in the anesthetic groups ([B/A]a) exceeded 1.0. [B/A]a exceeded [B/A]c by 18.7% in the 0.25 MAC halothane group (P less than 0.05), by 13.5% in the 0.31 MAC enflurane group (i.e., not significant), and by 17.3% in the 0.29 MAC isoflurane group (P less than 0.01). [B/A]a/[B/A]c decreased dose-dependently for each anesthetic group. These results suggest that low concentrations of halothane, enflurane, and isoflurane may enhance the performance of ddN mice in acquired avoidance training performed 30 min after anesthetic exposure. PMID- 1867424 TI - Sweating threshold during isoflurane anesthesia in humans. AB - Isoflurane anesthesia in humans markedly decreases the threshold temperature triggering peripheral thermoregulatory vasoconstriction (i.e., central temperature triggering vasoconstriction). However, it is not known whether the sweating threshold remains unchanged (e.g., near 37 degrees C), decreases along with the vasoconstriction threshold, or increases during anesthetic administration. Accordingly, the hypothesis that isoflurane anesthesia increases the thermoregulatory threshold for sweating was tested. Forehead sweating was evaluated in five healthy patients given isoflurane anesthesia. The sweating threshold was prospectively defined as the distal esophageal temperature at which significant sweating was first observed. Sweating was observed in each patient at a mean central temperature of 38.3 +/- 0.3 degrees C and an end-tidal isoflurane concentration of 1.1% +/- 0.2%. The interthreshold range (difference between vasoconstriction and sweating thresholds) without anesthesia is approximately 0.5 degrees C; isoflurane anesthesia increases this range to approximately 4 degrees C. PMID- 1867425 TI - Effects of volatile anesthetics on response to norepinephrine and acetylcholine in guinea pig atria. AB - The in vitro chronotropic and inotropic effects of norepinephrine and acetylcholine in isolated right and left guinea pig atria were examined in the absence and presence of halothane, isoflurane, and enflurane (0.6 and 1.2 MAC). All three anesthetics elicited dose-dependent reductions in contractile force and spontaneous pacemaker activity. The maximal developed tension observed in the presence of norepinephrine was not altered by the anesthetics and corresponding ED50 values increased only in the presence of 1.2 MAC halothane and 1.2 MAC isoflurane. The anesthetics did not affect (a) the maximal positive chronotropic effect of norepinephrine, (b) the ED50 values for its positive chronotropic effect, and (c) acetylcholine-induced negative inotropic and chronotropic actions and did not induce arrhythmic activity even in the presence of the maximally effective neurotransmitter concentrations. These findings indicate that in isolated guinea pig atria volatile anesthetics, in concentrations up to 1.2 MAC, do not alter the inotropic and chronotropic effects of norepinephrine or acetylcholine and do not induce arrhythmogenic action in the presence of the neurotransmitters. These data suggest that altered atrial responsiveness to adrenergic or muscarinic stimulation does not contribute to the development of anesthetic-induced cardiac arrhythmias. PMID- 1867426 TI - Age affects the pharmacokinetics of inhaled anesthetics in humans. AB - To define the effect of aging on the pharmacokinetics of volatile anesthetics, we determined the end-tidal and mixed expired anesthetic concentrations of isoflurane, enflurane, halothane, and methoxyflurane during 30 min of simultaneous administration and for 5-12 days of elimination in seven healthy young patients (31 +/- 1.8 yr [mean +/- SEM]) and in 11 healthy aged patients (73.2 +/- 3.1 yr [mean +/- SEM]). A five-compartment mammillary function was fit to the end-tidal and mixed expired anesthetic elimination data simultaneously using ordinary least-squares analysis. We assumed the compartments to represent the following tissue groups: lungs and pulmonary capillary blood (V1), vessel rich tissues (i.e., liver, heart, kidneys, and brain) muscle, an unidentified fourth compartment, perhaps fat adjacent to well-perfused tissues, and fat tissues. The tissue volumes and perfusions estimated for these compartments approximated values from the literature. In general, the volume of the fourth and fifth compartments increased with age, and perfusion to the second and fifth compartments decreased with age. Aging delayed anesthetic elimination and increased the apparent volume of distribution at steady state. These observations are compatible with decreased tissue perfusion and an increase in the ratio of fat/lean body weight in the elderly. Our mammillary analysis described the behavior of less soluble anesthetics such as isoflurane well, but that of highly soluble anesthetics such as methoxyflurane less well. PMID- 1867427 TI - Breathing pattern and occlusion pressure waveform in humans anesthetized with halothane or sevoflurane. AB - To examine the ventilatory effects of sevoflurane, breathing pattern, airway occlusion pressure waveform, and the mechanical variables of the respiratory system were determined in seven subjects anesthetized with sevoflurane and in an additional seven subjects anesthetized with halothane. All patients breathed 1 MAC of anesthetic using oxygen as the carrier gas, and the measurements were performed in the absence of surgical stimulation. The durations of inspiration and expiration were significantly longer during sevoflurane than during halothane administration. Tidal volumes were larger in the sevoflurane group than in the halothane group. Occlusion pressure waveforms were also markedly different between the two groups. Occlusion pressure during the initial 300-400 ms tended to be less in the sevoflurane-anesthetized than in the halothane-anesthetized subjects. There was no evidence of an active Hering-Breuer reflex with either anesthetic. Mechanical variables of the respiratory system were essentially identical between the two anesthetics. We conclude that (a) the ventilatory effects of halothane and sevoflurane are different, (b) the difference in the respiratory timing and depth of breathing originates from the action of the anesthetics on the central respiratory neural network, and (c) the different shape of the tracheal occlusion pressure may be largely due to the different effects of halothane and sevoflurane on the muscles of the rib cage. PMID- 1867428 TI - Deliberate hypotension with nicardipine or nitroprusside during total hip arthroplasty. AB - To induce deliberate hypotension during anesthesia, nicardipine was administered to patients undergoing total hip arthroplasty and was randomly compared with nitroprusside. Hemodynamic measurements were performed before and 10, 20, 30, and 60 min after starting to administer either nicardipine (n = 12) or nitroprusside (n = 12) (B, T1, T2, T3, and T4, respectively); at the end of drug infusion (T5); and 10, 20, and 60 min later (T6, T7, and T8, respectively). Plasma renin activity and catecholamine levels were measured at B, T1, T5, T6, and T7. In addition, plasma nicardipine concentration was measured in five patients at T1, T2, T5, T7, and T8. As with nitroprusside, nicardipine administration (1-3 micrograms.kg-1.min-1, after a titration dose of 4.7 +/- 1.5 mg) resulted in hypotension (up to -34% +/- 3%), a decrease in systemic vascular resistances (up to -49% +/- 4%), and increases in heart rate (up to +17% +/- 6%), cardiac index (up to +37% +/- 8%), plasma norepinephrine (up to +63% +/- 17%) and epinephrine (up to +232% +/- 68%) levels, and plasma renin activity (up to +336% +/- 207%). Ten and 20 minutes after discontinuation of the hypotensive drug, nicardipine led to persistent vasodilation and hypotension, which differed significantly from the hypertensive rebound observed after nitroprusside discontinuation, despite a similar increase in plasma renin activity and catecholamine levels. Our results indicate that after the infusion was terminated, the nicardipine-induced vasodilation was opposed to the vasoconstrictive effects of angiotensin II and catecholamines, thus avoiding hypertensive rebound.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867429 TI - Venous air embolism during lumbar laminectomy in the prone position: report of three cases. PMID- 1867430 TI - Lung laceration after tracheal extubation over a plastic tube changer. PMID- 1867431 TI - Hematoma after epidural anesthesia: relationship of skin and spinal angiomas. PMID- 1867432 TI - Electrical shock by dislodged spark gap in bipolar electrosurgical device. PMID- 1867433 TI - Is hypoxic pulmonary vasoconstriction exaggerated during one-lung ventilation in patients with patent ductus arteriosus? PMID- 1867434 TI - Buzz 'em or burn 'em. PMID- 1867436 TI - Foreign body from a Patil-Syracuse mask. PMID- 1867435 TI - Propofol and malignant hyperthermia. PMID- 1867437 TI - Do you think you could make yourself vomit? PMID- 1867438 TI - A method for withholding sedatives from patients before obtaining surgical consent. PMID- 1867439 TI - Triggering agents continued after masseter spasm: there is proof in this pudding! PMID- 1867440 TI - Pressure monitoring hose causes leak in anesthesia breathing circuit. PMID- 1867441 TI - Analgesic synergy between intrathecal opioids and local anesthetics. PMID- 1867442 TI - Addition of low-dose bupivacaine to epidural fentanyl infusion. PMID- 1867443 TI - Catheter spinal anesthesia and cauda equina syndrome: an alternative view. PMID- 1867444 TI - C1 esterase inhibitor deficiency: three presentations. AB - We have presented three patients representing three of the four reported forms of C1 esterase inhibitor deficiency. The C1INH deficiencies are in general distinguishable from each other and from other forms of angioedema by their complement patterns. The acquired C1INH deficiency must be part of the differential in patients without a family history of angioedema since it may precede the diagnosis of more serious medical conditions such as lymphoproliferative disorders. PMID- 1867445 TI - Pharmacists' substitution of slow release theophylline products. Committee on Drugs, American College of Allergy and Immunology. PMID- 1867446 TI - Effect of inhaled corticosteroid on bone density in asthmatic patients: a pilot study. AB - We investigated the effect of long-term inhaled (ICS) and oral corticosteroid (OCS) therapy on bone density by using single and dual photon absorptiometry. We studied a group of five asthmatic patients who inhaled an average of 326 micrograms/day of beclomethasone dipropionate equivalents for 50 months (range 36 to 62 months) and a control group of five asthmatic patients on OCS, who used 12.5 mg of prednisone equivalents daily for an average of 57 months (range 22 to 120 months). The ICS group's average bone densities relative to age and sex matched controls were 99.7%, 99.2%, and 90.0% for the radius, spine, and hip, respectively. The OCS group's average bone densities relative to age-matched and sex-matched controls were 94.4%, 85.4%, and 84.5% for the identical sites. A dose response relationship between the cumulative dose of ICS and the relative bone density was absent in the study group but demonstrable in the control group of asthmatics on long-term OCS therapy. These results suggest that ICS therapy, unlike OCS, may not induce bone loss at the doses used by our subjects. Further research is required to determine whether a single user of ICS with unusually low bone density measurements represents a biologic variant, or a subgroup of patients who are especially sensitive to the systemic effects of ICS. PMID- 1867447 TI - Lack of graft rejection in a renal transplant recipient with AIDS. AB - A renal transplant recipient developed evidence of human immunodeficiency virus (HIV) infection and severe opportunistic infection 44 months after transplantation. A strikingly reduced dosage of pharmacologic immunosuppression was required to maintain renal graft function. This may be the result of impaired helper T-cell function associated with the acquired immunodeficiency syndrome (AIDS). PMID- 1867448 TI - Late asthma caused by inhalation of Lepidoglyphus destructor. AB - We report the case of a grain worker who had immediate nasal and conjunctival symptoms and late-phase asthmatic reactions after handling stored grain. Allergy to one storage mite, Lepidoglyphus destructor, was demonstrated by skin testing, specific IgE, and bronchial provocation tests. Bronchial challenge with L. destructor provoked only a late phase asthmatic reaction without an immediate reaction despite the fact that immediate skin tests and specific IgE had been positive. Pretreatment with cromolyn sodium prevented any asthmatic reaction after bronchial challenge. An IgE immunologic mechanism could explain the clinical findings. PMID- 1867450 TI - Skin testing compared with in vitro testing for screening allergic patients. AB - A new FDA-cleared product has been introduced for screening suspected allergic patients using a small blood sample. The QUIDEL Allergen Screens (AS) are simple to use dipstick tests that measure allergen-specific IgE to ten of the most important regional allergens. We compared the results obtained by prick-puncture skin testing (ST) to those obtained with the AS on 103 patients with allergic symptoms. Of the 103 patients studied, there were 67 with positive skin tests, and 57 of those were positive by AS and ten were AS negative. Of the 36 with negative skin tests, 2 were positive by AS and 34 were AS negative. Compared with ST, the AS results gave a sensitivity of 85% and a specificity of 94% for identifying the allergic patient. Of the ten patients positive by ST but negative by AS, five were ST positive at the 1+ level; the other five were repeatedly negative by AS and confirmed negative by RAST. On an allergen basis, the ST and AS methods showed an 85% agreement. A subset of 24 patients from the foregoing group was studied for total IgE and allergen-specific IgE with products from both Pharmacia (P) and QUIDEL (Q). In this group of patients, skin test results gave seven patients negative and 18 patients positive to one or more allergens. While the overall Total IgE results were higher for ST patients, the Total IgE results alone did not effectively discriminate between ST-positive and ST-negative patients. The allergen-specific, however, results by both methods showed excellent agreement with the ST results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867449 TI - Cumulative incidence of atopic disorders in high risk infants fed whey hydrolysate, soy, and conventional cow milk formulas. AB - A recent increase in the prevalence of atopic disorders and the enormous costs of management of atopic patients have prompted attempts at prevention. We have examined the effect of exclusive breast feeding and of feeding different infant formulas on incidence of atopic disease in a prospective randomized controlled study. Seventy-two infants were recruited into each of the following groups: cow milk whey hydrolysate formula (NAN/HA) conventional cow milk formula (Similac), soy-based formula (Isomil), and exclusive breast feeding for greater than 4 months. The cumulative incidence of atopic eczema, recurrent wheezing, rhinitis, gastrointestinal symptoms, and colic were noted. Skin prick tests and radioallergosorbent tests for IgE antibodies to milk and soy were performed. At 12 and 18 months of age, the incidence of atopic eczema as also that of all atopic symptoms was significantly lower and similar in the breast-fed and whey hydrolysate groups, compared with the cow milk and soy formula groups. IgE antibodies were detected more often in the cow milk and soy formula groups, especially the former. Among symptomatic infants, fewer skin positive prick tests were seen in the soy group compared with the cow milk group. Our observations show that among infants at high risk of developing atopic disease because of positive family history, exclusive breast feeding or whey hydrolysate formula is associated with a lower incidence and thus a delay in the occurrence of allergic disorders compared with groups fed conventional cow milk or soy formulas. PMID- 1867451 TI - Potentially fatal asthma: the problem of noncompliance. AB - In spite of available pharmacologic therapy that controls even the most severe cases of asthma, the mortality rate from asthma continues to rise. Patients with potentially fatal asthma (PFA) must be identified and then treated in a manner that will prevent potentially fatal episodes of asthma. Such management will not result in control of patients with PFA when the patient is not compliant with the medical regimen. We report and classify ten PFA patients according to the apparent psychologic abnormality that resulted in, or contributed to the noncompliance. Some of these psychologic abnormalities in patients with PFA such as adolescent noncompliance, prednisonephobia or bipolar affective disorders may be responsive to a combination of medical and psychiatric management. Other psychiatric diseases that may occur in patients with PFA, such as antisocial personality disorders or schizophrenia, may have a poor prognosis even with combined medical and psychiatric care. The managing physician should be aware of the grave prognosis in such cases. PMID- 1867452 TI - Systemic cold urticaria in a five-year-old boy. AB - A 5-year-old white boy had a history of generalized urticaria on total body exposure to a cold environment. Standard ice cube testing was negative. Plasma analysis revealed the presence of cryofibrinogen. Systemic cold challenge with serial plasma assays for complement, histamine, and prostaglandin D2 disclosed an elevation and peak of plasma histamine and prostaglandin D2 levels after the onset of generalized urticaria with no change in serum complement levels. PMID- 1867453 TI - Prevalence of upper and lower respiratory conditions in the US population by social and environmental factors: data from the second National Health and Nutrition Examination Survey, 1976 to 1980 (NHANES II). AB - Data on respiratory conditions reported by sample persons 12 to 74 years of age in NHANES II were examined. The prevalence of upper respiratory conditions varied little between whites (N = 11,260) and blacks (N = 1,482): allergic rhinitis 9.8% versus 8.1%; chronic rhinitis 20.4% versus 19.2%. Except for "allergic rhinitis only," which was increased in whites, no racial differences were found for any upper respiratory condition, singly or in combination. The prevalence of lower respiratory conditions in whites and blacks were: asthma (A) 6.9% versus 9.2% P less than .05, chronic bronchitis (CB) 1.3% versus 0.8% P less than .05, and chronic cough (CC) 1.1% versus 0.7% P greater than .05. There was no racial difference in the prevalence of overall lower respiratory conditions (A + CC + CB). All upper and lower respiratory conditions peaked in 50 to 74-year-olds except for allergic rhinitis only (without asthma) which peaked in 25 to 49-year olds. Smokers reported all upper and lower respiratory conditions more often than nonsmokers, except for allergic rhinitis only (without asthma), which was reported less often by smokers. Females reported more allergic rhinitis in any combination, while males reported more asthma only (without allergic rhinitis). Sample persons living below poverty reported increased prevalence of chronic rhinitis, asthma, asthma only (without allergic rhinitis), and either allergic rhinitis or asthma. Residents of urban areas reported increased prevalence of allergic rhinitis and allergic rhinitis only (without asthma) while residents of rural areas reported increased prevalence of asthma only (without allergic rhinitis).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867454 TI - Dose tolerance study of fluticasone propionate aqueous nasal spray in patients with seasonal allergic rhinitis. AB - A multicenter, double-blind, parallel-group, dose-tolerance study was conducted to evaluate the safety of fluticasone propionate aqueous nasal spray, a potent new corticosteroid preparation. Ninety-seven adult patients with moderate to severe seasonal allergic rhinitis during the fall weed season received either placebo or fluticasone propionate in doses of 50, 200, or 800 micrograms twice daily for 4 weeks. Safety evaluations included adrenal function evaluation by morning plasma cortisol concentration, response to ACTH stimulation, and 24-hour urinary free cortisol excretion. There was no evidence of effects on adrenal function at any dose. The severity, nature, and frequency of adverse events were similar across all treatment groups, including placebo. Drug-related adverse events were consistent with local nasal irritation. The groups receiving fluticasone propionate showed greater improvement in nasal symptoms (obstruction, rhinorrhea, sneezing, and itching) than did the placebo group. The results demonstrate that fluticasone propionate aqueous nasal spray is safe in doses up to 1600 micrograms per day and effective in the treatment of seasonal allergic rhinitis. PMID- 1867455 TI - Effects of inhaled and oral corticosteroids on bone. PMID- 1867456 TI - Anaphylactoid reactions to radiocontrast material. PMID- 1867457 TI - [Current data on atmospheric pollutions]. AB - Atmospheric pollutions (AP) are very important for human health and ecological equilibrium. They may be natural or anthropogenic and in this later case they can appear outdoor or indoor. Urban air pollution is the most known form of AP. Its main sources are industries, individual and collective heating and now mainly automobile traffic in most cities. Classical AP indicators are SO2, particles, NOx, CO and Pb measured in networks. Important factors of AP are amounts of pollutants emitted and local climatic and meteorological characteristics. Health effects of AP peaks and of AP background levels are not well known. But generally, mean AP levels of SO2 and particles decreased in the last years in most towns as the consequence of collective actions on the three main sources of AP and on fuels, emission and immission levels; but more is wanted about motor cars. Progress are necessary for limitation of three major ecological risks: "acid-rain" (SO2 and NOx derivatives, ozone,...) which participates in lake and forest attacks; "green house" effects whose air CO2 concentration increase is the main responsible, and stratospheric ozone depletion mainly due to freons (CFC); the consequences of these two last phenomena are not well known but ecological and health risk exist. Besides, indoor air pollution (IAP) is very important because we live more than 20 h a day indoor. IAP may be occupational (a lot of chemical or biological agents) or not. In the later case air pollutants are very various: CO, NOx and particles from heating or cooking, formaldehyde from wood glue, plywood or urea-formol foams, radon and derivatives in some granitic countries, odd jobs products, cosmetics, aero-allergens of chemical or biological origins, microbes,... Environmental tobacco smoke (ETS) is also an important pollutant complex. Risks of IAP are real or potential: acute risk is obvious for CO, aero-allergens, formaldehyde, NOx,...); irritations are produced by ETS, formaldehyde, solvants,...; long term or potential risks are of concern for asbest, radon,... A complex and bad known pathology is described in a lot of modern buildings as the "Sick Building Syndrom". Indoor air quality is very dependant of the quality of ventilation and possible air treatment. It may be considered in all urban epidemiological studies about air pollution. PMID- 1867458 TI - [Consequences for public hospital of the law of December 20th 1988 (Huriet law), concerning the protection of persons used for biomedical researches]. AB - Does the public hospital have the capability of harbouring this research? In any case, it is an important mission entrusted to it by the Huriet law. But even before the law has come into effect (the date of applicability was initially set for January 1st 1990, postponed until June 1st 1990, and then further pushed back to December 31st 1990 due to the lack of publication of corresponding application decrees), its text has prompted many questions and much debate among numerous health sectors. We are limited in the extent to which we may estimate, within the context of the public hospital, the sphere of application and the ramifications of the Huriet law, particularly in the matters of expenses, the responsibility assumed by the hospitals' pharmacy, and the arrangement for the hospitals' management. In effect, while waiting for the expected creation of local committees for the protection of public health, the ethics committees which already exist in many hospitals carry on with their works in the spirit of this new law. The result is an accelerated awareness of the difficulties foreseen in putting this law into effect. It is these difficulties of application that we have tried to analyze. PMID- 1867459 TI - [Analytical study of the reciprocal influence of amino acids in mixtures on their determination]. AB - The behaviour of divers mixtures of amino acids in alkaline solution with copper II ions, determined with the help of the potential measurement taken by a copper electrode, was compared with that of a solution of isolated amino acids. The influence of the simultaneous presence of several of these compounds on the stoichiometry of the complexation was studied and discussed. PMID- 1867460 TI - [Preparation of oxime, hydrazone and dichloroacetamide derivatives. Researches of antiparasitic activity]. AB - Several oximes, hydrazones and dichloroacetamides were synthesized. The antiparasitic properties of these compounds were evaluated in vitro against two Protozoaires Entamoeba histolytica and Trichomonas vaginalis. PMID- 1867461 TI - [Combination of ethylene oxide with gums]. AB - Concerning combinaisons of ethylene oxide with any gums. The combinaisons of ethylene oxide are determined with any gums: tragacanthe, arabic, ceratonia, guar and sterculia. Among the stable compounds obtained with the gums sterculia, the author make mention of chloro-2 ethanol and ethyleneglycol. PMID- 1867462 TI - [Xanthogranulomatous pyelonephritis. Apropos of 42 cases]. AB - The authors report their experience of forty-two cases of xanthogranulomatous pyelonephritis. They point out the various difficulties of preoperative identification of such diseases by the imaging modalities. They also discuss the main pathogenic hypotheses proposed in the literature. PMID- 1867463 TI - [Genital prognosis of boys with bladder exstrophy or epispadias with incontinence. Apropos of 14 cases]. AB - Bladder exstrophy and epispadias with incontinence are associated with urinary tract and genital anomalies. The genital and sexual aspects were studied in 14 adolescent or adult males (12 exstrophies and 2 epispadias). The appearance of the penis was satisfactory in fifty percent of cases. Erections were always preserved but normal ejaculations were present in only one half of cases. Fertility potential was reduced. The improvement of surgical technique, and especially penile lengthening, has greatly improved sexual intercourse for these patients. PMID- 1867464 TI - [Genital prognosis of girls with bladder exstrophy or epispadias]. AB - The authors report ten cases of women with previous exstrophy of the bladder or epispadias with incontinence followed up to child-bearing age. Six of the ten females had urinary diversion and four retained their bladder and were continent. Three key aspects are considered: physical appearance of the external genitalia which was satisfactory in all cases; preservation of sexual function, known in only four of the ten cases and which was reported by these patients to be satisfactory, and finally, the ability to bear children. Three patients became pregnant resulting in four normal births (one patient had twins). Cesarean sections were recommended in patients with pregnancies at term. Cesarean should be performed systematically in patients with bladder reconstruction. PMID- 1867465 TI - [Pain and extracorporeal lithotripsy for calculi of the upper urinary tract]. AB - This study evaluates, 1) the pain induced by extracorporeal shock wave lithotripsy for renal stones using a piezo-electric shock wave lithotriptor (EDAP LT 01) and 2) the predictive factors for severe pain leading to an indication for analgesia. The relationship between extracorporeal shock wave lithotripsy intensity and pain intensity is evaluated by a numerical scale at the beginning of the session (T0), after 15 min (T15) and after 30 min (T30). At the end of the session, patients are categorized by one of us using a three-point scale which integrates the pain and the maximum tolerable intensity. These two types of evaluation are well correlated. Successive levels of stimulation are well discriminated by patients. Habituation is observed during the session for patients with low-level pain. In 28% of the patients, the intensity of pain required analgesia. Pain cannot be predicted by age, anxiety state, side of the stones and size, diameter of the contact between patient and convergence dome. In contrast, three parameters are correlated with the pain level: The L1 distance of renal parenchyma and the L2 distance skin-stone crossed by the piezoelectric waves, the size of the stone. The superior caliceal, middle caliceal and pelvic stones are significantly the most painful. These predictive variables can be easily measured before extracorporeal shock wave lithotripsy. PMID- 1867467 TI - [Pseudo-tumoral xanthogranulomatous pyelonephritis. Apropos of a case]. AB - The authors report the case of a 20 year old patient in whom the clinical findings combined with the radiological signs, suggested the diagnosis of renal cancer. The histological findings after nephrectomy established the diagnosis of xanthogranulomatous pyelonephritis. This disease may rarely give the appearance of a renal tumor. This points out the importance of identifying this lesion in preoperative staging to avoid carcinologic surgery and all of its difficulties. PMID- 1867466 TI - [Urological surgical effect of the repair of inguinal hernia using bilateral subperitoneal prosthetic mesh]. AB - In view of the increasing frequency of using subperitoneal bilateral prosthesis for inguinal hernia repairs, urologists should be aware of the genitourinary implications of this procedure: risk of infection due to potentially septic procedures on bladder or prostate, postoperative genitourinary complications, interval before subsequent trans-prosthetic surgical incision, operative tactical outcomes of subperitoneal pelvic fibrosis. PMID- 1867469 TI - [Prostatic cancer, a disease full of contrasts. Conference of 5 December 1990, Paris. Abstracts]. PMID- 1867468 TI - [Multiple condylomata of the urethra and bladder disclosing HIV infection]. AB - The authors report the case of a 26 year old man, in whom recurrent hematuria revealed the diagnosis of urethral condylomata with bladder extension, and HIV serology positive. This case reminds us that it is essential to search for immunodeficiency in every case of extensive or recurrent condylomata. The analysis of such cases in the literature allows discussion of the various clinical courses according to the Human Papilloma Virus types found in condylomatous tissues. PMID- 1867470 TI - Filament formation in Thermus species in the presence of some D-amino acids or glycine. AB - A number of strains of Thermus spp. changed morphology from rods of about 6 to 8 microns long to multicellular filaments (unsheathed trichomes) up to many hundreds of micrometres long with the addition of glycine or certain D-amino acids to the growth medium. Associated with this change was the formation of braided trichomes and occasionally true knots. Filament formation was reversible by the removal of the causal agent, but only if growth was possible. Electron microscopy suggested that the wall structure was not changed, but only that cells did not separate due to the continuous nature of the outer membrane layer. The filaments were thus multicellular. The constituent cells were similar in length to the normal rod-shaped cells. Filament formation by Thermus spp. may have applications in industrial scale culture of these extracellular enzyme-producing thermophilic bacteria. PMID- 1867471 TI - Ultrastructure and cell wall composition in cell division cycle mutants of Schizosaccharomyces pombe deficient in septum formation. AB - A number of temperature-sensitive cdc- mutants of Schizosaccharomyces pombe that are affected in septum formation were analyzed with respect to their ultrastructure and the composition of their cell wall polymers. One mutant strain, cdc 16-116, has a cell wall composition similar to the wild type (strain 972 h-). However two other mutants, cdc 4 and cdc 7, show a higher galactomannan content and a lower alpha-glucan content. In all the mutants tested, total glucose incorporation, protein, RNA and DNA synthesis increased similarly to wild type over 3 1/2 h. After 2-3 h of incubation at the non permissive temperature 35 degrees C-, cell numbers remained constant although, increases in optical densities at 600 nm were observed. According to scanning electron microscopy, the mutants had aberrant shapes after 5 h of incubation at 35 degrees C. Transmission electron microscopy showed that cdc 3 is unable to complete septum formation. cdc 4 showed the most varied morphological shapes and aberrant depositions of cell wall material. cdc 8 exhibited a deranged plasma membrane and cell wall regions near of cell poles; an abnormal septum and several nuclei. cdc 7 showed elongated cells with several nuclei and with an apparently normal cell wall completely lacking in septum and septal material. cdc 16 showed more than one septum per cell. PMID- 1867473 TI - Cryptococcus yarrowii sp. nov., a novel yeast species from Portugal. AB - A novel species of the basidiomycetous genus Cryptococcus is described as Cr. yarrowii based on the study of an isolate from a decayed mushroom collected in Portugal. DNA-DNA homology with the type strain of the phenotypically similar species Cr. albidus was 10 +/- 2%. PMID- 1867472 TI - Occurrence and significance of precipitating antibodies against thermophilic actinomycetes in the sera of dairy herd workers, Nangali, Delhi. AB - The study was prompted by the lack of information on the role of thermophilic actinomycetes in hypersensitivity pneumonitis in India. It reports the occurrence of precipitating antibodies against clinically important thermophilic actinomycetes in the sera of a population sample of dairy herd workers, Nangali, Delhi. Of 112 workers investigated, 28 (25%) showed precipitins against Faenia rectivirgula, 4 (3.2%) against Saccharomonospora viridis, 2 against Thermoactinomyces thalpophilus and one each against T. vulgaris and T. sacchari. The results of enzyme-linked immunosorbent assay (ELISA) indicated that IgG antibody activity against F. rectivirgula was significantly higher in the symptomatic group than in the asymptomatic group (p less than 0.05) of workers and the controls (p less than 0.01). Significant difference in F. rectivirgula IgG activity was also obtained between the precipitin-positive symptomatic group and the precipitin-positive asymptomatic group (p less than 0.05). In strong contrast, the IgG antibody activity against T. thalpophilus was found to be uniformly low. A limited aeromicrobiological sampling of the dairy farm revealed S. viridis (55.8%) to be the commonest species followed by T. vulgaris (19.2%), T. thalpophilus (18.5%), F. rectivirgula (5%) and T. sacchari (1.5%). On the basis of suggestive clinical and laboratory findings, farmer's lung disease was suspected in four dairy herd workers. A comprehensive clinical evaluation including pulmonary function studies on the dairy herd workers and their long term follow-up is indicated to determine the extent of respiratory morbidity caused by F. rectivirgula, S. viridis, T. thalpophilus, T. sacchari and T. vulgaris in India. PMID- 1867474 TI - Chitinase activity in germinating cells of Mucor rouxii. AB - Chitinase activity in germinating cells (4 h cultures) of Mucor rouxii was studied. The enzyme activity was recovered in a high speed supernatant of cell homogenates. No activity was detected in the mixed membrane fraction or in the cell walls. Maximum activity was observed at pH 7.6 and at 30-35 degrees C using the chromogenic assay with chitin azure. The latter was digested by GS-chitinase in a manner dependent on substrate concentration and time of incubation. As with other chitinases, GS-chitinase was much more effective against nascent than against preformed chitin. The main product of nascent chitin digestion was diacetylchitobiose, although significant amounts of the trimer were also detected in the hydrolyzates. Allosamidin, an insect and fungal chitinase inhibitor, strongly inhibited hydrolysis of nascent chitin but not of chitin azure by GS chitinase. The drug failed to inhibit the germination and the ensuing growth of the fungus. Results are discussed in terms of the possible role of GS-chitinase in germination. PMID- 1867475 TI - Fermentation of L-tartrate by a newly isolated gram-negative glycolytic bacterium. AB - Enrichments on L-tartrate from a freshwater lake sediment yielded a pure culture of anaerobic bacterium designated strain 16Lt1. The rod-shaped organism was motile, did not form spores, and had a gram-negative wall structure. No cytochromes were detected. The mol % G + C of the DNA was 58. The new strain was microaerotolerant, and grew optimally at 30 degrees C and neutral pH in freshwater medium. A wide range of carbohydrates was fermented, with formate, acetate, ethanol, lactate and succinate being the end-products detected. L tartrate and citrate were fermented to formate, acetate and CO2. L-tartrate was fermented by the dehydratase pathway, and glucose by the Embden-Meyerhof-Parnas pathway. Fumarate was reduced, but nitrate, sulfate, sulfur and thiosulfate were not used as terminal electron acceptors. Glucose metabolism was constitutive, whereas L-tartrate-degrading activity was inducible. When glucose and L-tartrate were both present as substrates, growth was diauxic with glucose being metabolized first. The growth rate and growth yield were higher on glucose than on L-tartrate. Strain 16Lt1 has been deposited with the Deutsche Sammlung von Mikroorganismen as 'Bacteroides' sp. DSM6268. PMID- 1867476 TI - Mortality of marine bacterial strains in seawater. AB - As an approach for assessing the dynamics of bacterial population in seawater, the survival of five isolated marine bacteria strains was assessed by the disappearance of radioactivity in the cold trichloroacetic acid (TCA)-insoluble fraction from a previously 3H-labeled culture. Metabolic activity during survival experiments was assessed by the measurement of electron transport system (ETS) activity. Fractionated filtration was used to assess the grazing mortality. The particulate fraction that passed 2.0 microns and was retained in 0.2 microns was the main cause of mortality. PMID- 1867477 TI - Ultrastructural study of the skin in Sjogren-Larsson syndrome. AB - The ichthyosiform skin and the uninvolved skin of a 5-year-old Japanese female with Sjogren-Larsson syndrome were examined by light and electron microscopy to elucidate the keratinization disorder. Light microscopically, the epidermis of the ichthyosiform skin showed acanthosis, papillomatosis and hyperkeratosis. The horny cells had a basket-weave appearance. The granular cell layer was slightly thickened. Slight round cell infiltration and vascular dilatation were seen in the upper dermis. The uninvolved skin was histologically normal. Electron microscopically, in both ichthyosiform and uninvolved skin, abnormal lamellar or membranous inclusions were present in the cytoplasm of horny cells of the epidermis. These inclusions appeared to be derived from some of the lamellar bodies and/or abnormal membranous structures found in the cytoplasm of spinous and granular cells. Mitochondria in the epidermal basal cells were more numerous in the ichthyosiform skin than in the uninvolved skin. These findings indicate that, whether the skin is involved or not, the epidermis of the patient with this disorder may always have a structural abnormality, which may be genetically determined. Local environmental factors may play a role in inducing the acanthosis and papillomatosis of the epidermis. PMID- 1867478 TI - Inhibitory effect of azelaic acid on neutrophil functions: a possible cause for its efficacy in treating pathogenetically unrelated diseases. AB - It has been shown that acne, hyperpigmentation and lentigo malignant are more or less related pathogenetically to reactive oxygen species (ROS). It has recently been reported that azelaic acid is effective in treating these conditions and that it possesses anti-enzymatic and antimitochondrial activity, including cytochrome-P450 reductase and 5 alpha-reductase in microsomal preparations with nicotinamide adenine dinucleotide phosphate (NADPH). We therefore investigated the effects of azelaic acid on human neutrophil functions, such as chemotaxis, phagocytosis and ROS generation. ROS generation in a cell-free system was also assessed. The results revealed that neutrophil chemotaxis and phagocytosis as well as ROS generated in a xanthine-xanthine-oxidase system were not significantly changed in the presence of azelaic acid. However, azelaic acid markedly decreased O2- and OH. generated by neutrophils. It may be concluded that the reported clinical effectiveness of azelaic acid is partly due to its inhibitory action on neutrophil-generated ROS, leading to a reduction both in oxidative tissue injury at sites of inflammation and in melanin formation. PMID- 1867479 TI - Lipids, proteins and corneocyte adhesion. AB - Three factors were examined for their relative contribution to corneocyte cohesion in normal adult pig ear: (1) extracellular lipids derived from membrane coating granules (MCG); (2) corneosomes (modified stratum corneum desmosomes); and (3) corneocyte covalently bound lipid envelopes. Cohesion strength of the outer stratum corneum was measured directly by cohesometry, then altered by removing MCG lipids with solvents of varying potency. Cohesion changes were related to degree of lipid removal and ultrastructural alterations. Trypsin was also used to see if proteolysis of corneosomes promoted squame shedding. Potent solvents increased cohesion in relation to the amount of MCG lipid extracted. Tighter cohesion was due to fusion of the outer leaflets from covalently bound lipid envelopes on adjacent corneocytes. However, lipid envelopes are unlikely to mediate normal stratum corneum cohesion since MCG lipids play a significant anti cohesive role preventing their apposition. Mild solvents partially removed MCG lipids causing a slight decrease in cohesion compared with untreated samples. This suggests a minor cohesive role for MCG lipids, consistent with maintaining their barrier function. We believe that corneosomes are the major determinant of stratum corneum cohesiveness because, in untreated skin, both cohesion and the number of corneosomes increased from the surface towards the granular layer. Furthermore, corneosome digestion with trypsin induced superficial squame shedding. PMID- 1867481 TI - Differential analysis of the human anagen hair apparatus using lectin binding histochemistry. AB - Cell differentiation in the human anagen hair apparatus was examined by lectin binding histochemistry using seven different lectins: Con A, WGA, RCA-I, PNA, SBA, DBA and UEA-I. Con A and WGA positively stained almost all the cells in the hair apparatus. RCA-I and PNA positively stained the outer cells of the outer root sheath (ORS), but they did not stain the innermost cells (IMCs) of the ORS in the suprabulbar region. However, in the isthmus region, the IMCs showed positive staining with RCA-I, and more intense staining with PNA than that of the outer ORS cells. The ORS cells, including the IMCs, were negative with SBA and DBA below the suprabulbar region, whereas the IMCs became more strongly positive with these two lectins than the other ORS cells in the isthmus region. UEA-I strongly stained the IMCs, but not the outer ORS cells in the hair bulb. The latter cells became positive for UEA-I above the suprabulbar region. These findings indicate that the surface glycoconjugate distribution of the IMCs differs from that of the outer ORS cells. It is concluded that the IMCs of the ORS may undergo an independent cell differentiation process. PMID- 1867480 TI - Sugars protect desmosome and corneosome glycoproteins from proteolysis. AB - Adhesional glycoproteins of desmosomes possess asparagine-linked, complex oligosaccharide side chains. We investigated the potential of these sugars to protect the core proteins of desmosomes and corneosomes (modified stratum corneum desmosomes) against proteolysis. Isolated pig ear epidermis was exposed sequentially to individual hydrolases, and their effect monitored ultrastructurally. Two major steps were employed: (1) glycosidases, to remove stepwise the sugars in a typical complex oligosaccharide chain; and (2) proteolysis using both endopeptidases and an exopeptidase. Controls were exposed to the same sequence of buffers, but without enzymes. Proteases alone induced no major changes in desmosomes or corneosomes compared with controls. Glycosidases alone, or proteases followed by glycosidases, caused mild fragmentation of the desmosomal interspace, but no widening. However, dramatic changes occurred when glycosidase treatment was followed by proteolysis. The interspace of both desmosomes and corneosomes was extensively digested, and consequently widened, causing loose packing of the epidermis. These findings indicate that sugars are potentially anti-proteolytic in both desmosomes and corneosomes. Sugars may, therefore, be a factor in preventing premature desquamation, by protecting desmosomes and corneosomes against extracellular proteases derived from membrane coating granules. PMID- 1867483 TI - Lack of demonstrable effect of cyclosporin A on human epidermal Langerhans cell function. AB - There is controversy about whether Cyclosporin A (CsA) affects antigen-presenting cell function. Within the skin, Langerhans cells (LC) are very potent antigen presenting cells. We investigated the effect of CsA on alloantigen presentation by human LC using the in vitro mixed skin-cell lymphocyte reaction (MSLR). MSLR (6 day cultures) were performed in round-bottomed microplates and lymphocyte proliferation was assessed by 3H-thymidine incorporation during the final 18 h of culture. When CsA was added into the wells a dose-dependent inhibition of T-cell proliferation occurred. Similar results were obtained when crude or LC-enriched epidermal cells (EC) were incubated for 2 h in the presence of CsA and extensively washed. The inhibition caused by CsA treatment of EC was not overcome by the addition of indomethacin. However, when CsA-treated EC were added to a fresh MSLR, T-cell proliferation was impaired. Furthermore, supernatants from CsA treated EC, that had been kept for 6 days in culture medium, were able to inhibit the T-cell proliferative assay. These supernatants were found to contain CsA by a radioimmunoassay. From these results, it is clear that inhibition of MSLR obtained after CsA pulsing of EC suspensions can be explained by a release of the drug into the supernatant and thus by a direct effect on T cells. These findings contrast with recent reports showing a direct effect of CsA on human LC function. PMID- 1867482 TI - Role of skin surface lipids in UV-induced epidermal cell changes. AB - Ultraviolet irradiation is capable of affecting skin surface lipids, especially squalene and cholesterol, both in vitro and in vivo, with generation of active lipoperoxides. The photodecomposition of the skin lipid component was carefully evaluated by capillary gas-chromatography. The effects of UV-induced lipoperoxides on human keratinocytes in culture and on guinea pig ear slices were compared with those of synthetic lipoperoxides, i.e. cumene hydroperoxide and 13 hydroperoxylinoleate. A time- and dose-dependent effect on protein synthesis and mitotic activity was observed. In cell culture low concentrations (0.05-5 micrograms/ml) of peroxidated squalene and synthetic lipoperoxides stimulated the incorporation of radiolabelled thymidine and phenylalanine, while higher concentrations (greater than 10 micrograms/ml), or longer periods of treatment, induced cellular damage. In guinea pig ear slices, the lipoperoxides (5-50 micrograms/ml) increased aminoacid incorporation and the number of epidermal pigment cells; higher concentrations (greater than 100 micrograms/ml) caused a derangement of epidermal structure. The results suggest that UV irradiation of skin generates lipoperoxides from the surface lipids which, in vitro, are capable of producing a number of changes in epidermal cells. PMID- 1867484 TI - [Telesugery and its teaching and health care implications]. PMID- 1867486 TI - [Psoas fixation of the bladder. An efficient aid in cases of repeat surgery of the uretero-vesical junction]. AB - We reviewed our experience with 6 patients (5 males, 1 female) aged 3 to 10 years in whom psoas hitch of the bladder was performed in the course of repeated surgery of the vesicoureteral junction. All patients had previously undergone an operation on the distal ureter and presented an evident shortening of its length. After ureteral reimplantation in 4 patients (3 were Hendren's procedure and 1 Cohen's reimplantation), the reflux either persisted or became worse and the remaining 2 patients (posterior urethral valves) underwent cutaneous distal ureterostomy. In all cases the psoas hitch procedure successfully resolved the ureteral defect, provided the bladder with a new surface for a submucosal tunnel of suitable length and diameter, and permitted reimplantation of the ureter without traction or possibility of bending. The psoas hitch procedure is a simple and effective alternative in the management of distal ureter length defects. Although it has precise indications, it can have broad applications when combined with other techniques (TUU). However, the approach should be one of caution in those cases that also require surgery of the contralateral distal ureter. PMID- 1867485 TI - [Closed renal trauma: 287 cases. Evaluation of treatment and long-term follow up]. AB - We evaluated 287 cases of blunt renal trauma that had been treated at the Urology Department of the Valle de Hebron Hospital from 1974 to 1987. Data gleaned from patient work up, diagnosis and treatment during the acute phase are presented, highlighting the early and long-term results. Patient follow-up ranging from 1 to 10 years and data from statistical analyses show that conservative treatment achieved better early and late results than surgical treatment of the compromised renal unit. Hypertension was an uncommon secuela in our series (1% incidence). Evaluation with radioisotopes has proved to be the most reliable diagnostic method in the long-term assessment of secuelae in the renal unit. PMID- 1867487 TI - [Primary bladder adenocarcinoma: retrospective study of 11 cases and general review]. AB - Eleven cases of primary adenocarcinoma of the bladder are described herein. Eight had a glandular pattern, 1 was papillary and 2 were comprised of signet ring cells (one had areas of colloid carcinoma). One of the cases, originating from the urachus, also showed colloid areas and a glandular pattern. Forty-five percent of the cases were moderately differentiated and the remaining 55% were poorly differentiated. In all cases the tumor had areas of adenocarcinoma in more than 2/3 of its extent. All but two cases revealed muscle layer infiltration at the time of diagnosis. Two patients were submitted to radical cystectomy, lymphadenectomy and Wallace II cutaneous ureteroileostomy, 1 patient underwent partial cystectomy and lymphadenectomy, and 6 were submitted to transurethral resection. Excision of the urachal tumor was by en bloc partial cystectomy. The 5 year survival of patients with infiltrating tumors, excluding the urachal tumor, was 33%, 67% died within the first year of follow-up. The only evaluable case of superficial adenocarcinoma is alive and tumor-free at 94 months. Primary adenocarcinoma of the bladder is an aggressive tumor. Although it may be superficial at the time of diagnosis, it soon develops into an infiltrating tumor if untreated. Treatment and survival depend on tumor stage. Superficial or minimally infiltrating tumors warrant treatment by deep transurethral resection up to the pericystium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867488 TI - [Bladder adenocarcinoma. Presentation of 3 new cases]. AB - Three additional cases of primary adenocarcinoma of the bladder, an uncommon tumor type, seen at our department during the past years are described. These may arise from urachal remnants or metaplastic changes occurring in bladders with cystitis cystica or glandularis. Clinically, their behaviour is not unlike the rest of the infiltrating urothelial tumors. Treatment is by partial cystectomy for urachal adenocarcinoma and radical cystectomy for those arising from other sites of the bladder. Radio- and chemotherapy have a very limited efficacy in this tumor type. PMID- 1867489 TI - [Leydig cell tumor: presentation of 3 new cases with a benign course]. AB - Three cases of Leydig cell tumor are described. Patient ages were 27, 44 and 55 years, respectively. The first two patients consulted for a testicular mass and the third patient presented with gynecomastia, an incidental finding during the ultrasound work up of a hydrocele. Hormonal evaluation revealed a marked serum testosterone level in one case, whereas in another case it fell within the lower limits of normal ranges. No evidence of dissemination was observed in all patients. Treatment was by radical inguinal orchiectomy in all patients. The pathological analysis of the surgical specimens revealed Leydig cell tumor with no histologic evidence of malignancy. A follow-up of 32, 14 and 10 months, respectively, revealed no evidence of tumor recurrence in all patients. The clinical and histologic features and treatment of this disease process are described. PMID- 1867490 TI - [Prognostic factors in 243 transitional carcinomas of the bladder (I): clinical and macroscopic parameters of the tumor]. AB - A retrospective study was undertaken in 243 cases of transitional cell carcinoma of the bladder to determine the correlation of clinical parameters (sex, age, symptoms and duration of the disease) and tumor gross anatomic features (cystoscopic aspects, tumor number, size and site) with survival. The study comprised 148 superficial carcinomas and 95 infiltrating carcinomas of the bladder. The following clinical parameters were observed to influence survival of patients with superficial or deep tumors: patient age (worse prognosis for those over 60 years) and initial symptoms (better prognosis for those whose presenting symptom was hematuria). With regard to tumor gross anatomic features, a correlation was observed between the cystoscopic aspects of the tumor and type of infiltration in 80% of our series (1 error out of 5 cystoscopies). A worse prognosis was observed for multiple lesions only in those with superficial tumors. Tumor site and size did not influence survival in this series of 243 transitional cell carcinoma of the bladder. PMID- 1867492 TI - [Treatment of bladder endometriosis using the Nd-Yag laser]. AB - The good results achieved in the treatment of gynecological endometriosis via laser laparoscopy prompted us to perform endoscopic Nd:Yag laser photocoagulation in the present case of symptomatic vesical endometriosis described herein. To our knowledge, this is the first reported case in the world literature. PMID- 1867491 TI - [Prognostic factors in 243 transitional carcinomas of the bladder (II): microscopic parameters of the tumor and staging]. AB - A retrospective study was undertaken in 243 cases of transitional cell carcinoma of the bladder to determine the correlation of tumor microscopic features (mitotic index, histologic grade, internal border of tumor growth, lymphocyte infiltration, necrotic and vascularized areas) and stage with survival. The study comprised 148 superficial tumors (131 papillary, and 17 non-papillary) and 95 deep infiltrating tumors (34 papillary and 61 non-papillary or solid tumors). With regard to the superficial tumors, survival was influenced by the mitotic index (a greater number of mitoses correlated with a worse prognosis), histologic grade (a higher histologic grading correlated with a worse prognosis), internal border of tumor growth (the expansive tumor type showed a better prognosis), and necrosis (wide areas of necrosis correlated with a lower survival rate). Furthermore, a worse prognosis was observed for the non-papillary or solid tumors. Lymphocyte infiltration, however, was not observed to influence survival. As for the deep infiltrating tumors, survival was influenced by the histologic grade, internal border of tumor growth, lymphocyte infiltration (a greater lymphocyte infiltration correlated with a better prognosis), necrosis, and tumor type (papillary or non-papillary). The mitotic index or vascularization showed no influence on survival. A higher tumor stage correlated with a worse prognosis. The prognosis for non-papillary (solid) superficial tumors overlaps that of infiltrating tumors. For this reason, special attention should be focused to these tumors. PMID- 1867493 TI - [Prolonged erections after diagnostic injection of papaverine chlorhydrate]. AB - We analyzed the incidence of prolonged erection (PE) in 495 impotent subjects following intracavernous papaverine chlorhydrate injection to evaluate sexual dysfunction. Patient course was individually assessed. The overall the incidence of PE was 5.05%. The etiology of sexual dysfunction was psychogenic in all cases. No evidence of dose- or age-related PE was observed. Fibrosis of the corpus cavernosum, although more prevalent in PEs greater than 6 hours, was also observed in PEs of a shorter duration. This suggests that a probable predisposing factor might previously be present in some patients. None of the different methods utilized to achieve penile detumescence appears to afford any significant advantage. PMID- 1867494 TI - [Cavernotomy]. AB - Corpus cavernosal dilatation in patients undergoing implantation of a penile prosthesis may occasionally be impossible to achieve with the Edgart dilator owing to sclerosis. For this reason, we have developed the cavernotome, a specially designed dilator that allows for easy dilatation of the corpus cavernosum. Its salient edges and grooves permit cutting through the sclerotic areas without difficulty. It is indispensable for placement of an anatomic penile prosthesis in these cases. PMID- 1867495 TI - [The rigidometer]. AB - Fifty patients with erectile dysfunction were evaluated with the Rigidometro (CUASBA) penile rigidity monitor and the data were compared with those obtained with the erectometer device for nocturnal monitoring with the Ambulatory Rigidity Tumescence Monitor (ART 1000, Surgitex) penile rigidity monitoring following intracavernal injection of vasoactive agents. Similar results were observed. In our view, the Rigidometro (CUASBA) provides reliable information comparable with those provided by other monitoring devices. It gives very precise data on the quality of erection achieved. It is inexpensive and easy to-use. All the foregoing make it a useful tool in the diagnosis and evaluation of erectile dysfunction. PMID- 1867496 TI - [Leydig cell tumor associated with gynecomastia]. AB - We report a case of interstitial cell or Leydig cell tumor, an uncommon tumor type, that presented with evident feminizing features and acute testicular inflammatory process which warranted hospitalization. The literature is reviewed highlighting the most important aspects of this condition. PMID- 1867497 TI - [Rupture of the excretory tract to renal cyst, its sequestration and later infection, as a complication of ureteral lithiasis]. AB - We report on a case of infected solitary renal cyst following rupture and communication of the excretory tract from a ureteral calculus. The etiopathogenic mechanisms, the diagnostic difficulties encountered in this uncommon disease process, and the usefulness of radiologic and ultrasound assessment are discussed. PMID- 1867498 TI - [Hypernephroma and bladder leiomyosarcoma. Report of a case]. AB - We report on a patient with two primary and synchronous urological tumors (hypernephroma and leiomyosarcoma of the bladder). Patient follow-up of 14 months revealed no evidence of tumor recurrence. The clinical, diagnostic and therapeutic aspects of this rare tumor of the bladder are highlighted. We consider surgical treatment mandatory and radio- and chemotherapy adjunctive treatment modalities. PMID- 1867499 TI - [Acquired ichthyosis caused by bladder neoplasia. Presentation of the 1st case in Cuba]. AB - Ichthyosiform dermatoses comprise a heterogeneous group of cutaneous disease characterized by keratin disorder that clinically manifests as dry, rough and scaly skin. The acquired form of ichthyosis has principally been associated with neoplastic disease. It has also been described in association with other disorders and as drug-induced cutaneous manifestations. We report on a patient with a bladder tumor who developed acquired ichthyosis, a complication and presenting feature of the underlying neoplastic condition. The clinical manifestations and associated conditions are described. To our knowledge, this is the first case of acquired ichthyosis from a bladder tumor reported in Cuba. PMID- 1867500 TI - The use of the Dornier MPL-9000 lithotripter in the treatment of gallbladder and renal stones. Early experience. AB - The experience of two units (Gastroenterology and Urology) of Clinica La Luz, Madrid, in the treatment of gallbladder and renal lithiasis using the Dornier MPL 9000 lithotripter is reported herein. This lithotriptor has been utilized in the treatment of all cases of gallbladder calculi for which it is indicated and renal calculi localized high up (kidney), and in those cases that are difficult to treat with other lithotriptors such as patients with kyphoscoliosis, radiolucent calculi, elderly patients, children, etc.). During the first year the gallstone lithotripsy unit was utilized, 401 patients were referred for treatment. Of these, 180 met the criteria for patient selection. (Over 360 have been treated to date.) Sixty of these 180 patients had a single gallstone of up to 2.5 cm. These 60 patients were selected for the study since they comprised a group where the best results could be expected. The aim of studying this patient group was to evaluate the results achieved by lithotripsy and the short and medium-term outcome in this ideal group of patients. Concerning renal lithiasis, these are the first 100 cases treated with the MPL-9000 (currently over 420 have been treated). Eighty cases had a single calculus (60 caliceal and 20 pyelic), 15 had multiple calculi, and 5 had a staghorn stone. Treatment for gallbladder and renal lithiasis was exclusively by shock waves; i.e., as monotherapy with no other auxiliary procedure. The average number of shock waves used was 2,350 with a mean kV of 18 for gallbladder lithiasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867501 TI - [The professional future of Spanish urologists]. PMID- 1867502 TI - [English and Spanish nomenclature of catheters and other urological instruments]. AB - We analyze names given to urologic devices that are apparently similar in English and Spanish but with different meanings. The translation of the commonest terms for instruments and some problematic words are reviewed. Although some of the equivalents are a convention, it is interesting to know the more widely used nowadays. PMID- 1867503 TI - [Intermittent aspiration in the treatment of urinary fistulas following cutaneous ureteroileostomy]. AB - Two patients who had developed a urinary fistula following cutaneous ureteroileostomy are described herein. The foregoing condition was successfully treated conservatively with intermittent aspiration via the stoma. This treatment modality was generally performed using regular periods of application and aspiration pressure. The common complications of cutaneous ureteroileostomy are briefly described. Attention is focussed on urinary fistula, an uncommon complication, and the possibility of resolving the foregoing condition in a short period of time by aspiration via the cutaneous stoma before resorting to endourologic or surgical alternatives. PMID- 1867504 TI - [Morphometric study of transitional carcinoma of the bladder (I): analysis of 148 superficial tumors]. AB - A morphometric study of the tumor cell nucleus was performed in 148 cases of superficial transitional cell carcinoma of the bladder. Of these, 131 were papillary and 17 were nonpapillary tumors. Our methodology is compared with those described elsewhere. With regard to papillary tumors, the nuclear size of the internal papilla near the stroma was found to be greater than that of the external papilla near the bladder lumen. Tumor cells with internal papillary nuclear size less than or equal to 28 microns 2 appeared to have a better prognosis. Thus, nuclear measurements in this area must be performed in future studies. No conclusive data could be obtained relative to the nonpapillary tumors. For both papillary and nonpapillary tumors, the higher the histologic grade, the greater the nuclear size, the differences being statistically significant. PMID- 1867505 TI - [Morphometric study of transitional carcinoma of the bladder (II): analysis of 95 infiltrating tumors]. AB - The nuclear size of 95 infiltrating carcinomas of the bladder were studied morphometrically. There were 34 of the infiltrating papillary type and 61 pure infiltrating tumors. The nuclear size was found to be greater deeper into the tumor. Similarly, the higher the histologic grade, the larger the nuclear size. Grade IV tumors, however, were not greater than grade III. The foregoing finding prompted us to classify grade IV tumors as undifferentiated rather than as transitional cell tumors. A better prognosis was observed for stage T2 and T3A tumors with a nuclear size less than or equal to 30 microns 2. PMID- 1867506 TI - [Bladder tumors in patients under 40 yr of age. Our experience and review of the literature]. AB - During a period spanning 11 years, 392 patients diagnosed as having tumor of the bladder were treated at our department. Of these, 9 were patients under age 40. We compared the anatomopathological features and course of the disease. The foregoing condition was suspected on the basis of the urographic findings. We emphasize the need to perform endoscopic inspection and urinary cytology before discarding the presence of a bladder tumor. The anatomopathologic conditions of anaplasia and infiltration are frequently more favourable in this younger patient group, indicating a better prognosis. However, the natural history of tumors with histopathologically similar features is not influenced by age. PMID- 1867507 TI - [Urinary incontinence in the elderly: clinical and urodynamic review of 195 cases]. AB - One hundred ninety-five male and female patients over 65 years old presenting with urinary incontinence were evaluated by clinical and urodynamics. Urinary incontinence was in the form of urgency-incontinence in 68% of the cases, incontinence at cough in 26%, and urinary incontinence which the patient referred to no specific situation in 6%. Among the different urodynamics data, bladder instability was the most common (73%). Urinary stress incontinence was observed in 35% of the cases. Bladder instability was demonstrated in 77% of the cases with urgency-incontinence and in 69% of the cases with incontinence not referred to a specific situation. All the male patients with lower urinary tract obstruction had urgency-incontinence. Stress incontinence was demonstrated in 60% of the cases with incontinence at cough. Stress incontinence was not observed in male patients without associated diseases. The associated neurological disorder was accompanied by bladder hyperreflexia in 90% of the cases. A prior adenomectomy or hysterectomy was associated with a greater number of cases with stress urinary incontinence, accounting for 62% in both males and females. PMID- 1867508 TI - [Long-term results of endourological treatment with and without ESWL in cystine lithiasis]. AB - From 1984 to 1989, 15 patients with cystine calculi were treated by endourologic procedures and/or extracorporeal shock wave lithotripsy (ESWL). During this period the patients required 38 hospitalizations, a total of 74 calculi were treated localized to 61 sites: pelvic 21, caliceal 13 and 27 were multiple. The diagnosis was confirmed by a 24 hour cystinuria (3.595 muMol/24 h. average) and analysis of the stone fragments. Stone disruption was achieved in 17 of 38 cases (44.7%). ESWL as monotherapy was utilized in calculi less than 15-20 mm. in diameter; complete removal was achieved in of 18 cases. Percutaneous surgery (PC) was used alone or in combination with ESWL for large calculi or when ESWL failed to achieve stone fragmentation. Complete stones removal was achieved in 5 of 9 cases using PC as monotherapy and in 5 of 10 in combination with ESWL. There were 23 recurrences during this period; 13 patients with residual stone fragments and 10 patients that were stone-free. The present study reports our experience in the treatment of cystine calculi by PC and/or ESWL and the long-term results achieved with the respective treatment modalities. PMID- 1867509 TI - [Priapism secondary to phenothiazines]. AB - We report two cases of priapism in patients previously treated with neuroleptic agents. None of these patients had a previous history of urological or hematological disorders. These two patients warranted emergency treatment by punction-aspiration of the corpora cavernosa and posterior cavernospongiosa shunt. The foregoing approach achieved penile detumescence in both cases. Excellent results were achieved relative to erectile function in one patient. Although the mechanism responsible for phenothiazine-induce priapism has as yet not been elucidated, it has been suggested that this might be due to adrenergic block which directly inhibits the sympathetic impulse of detumescence. PMID- 1867511 TI - [Renal abscess. Medical treatment]. AB - We report a case of renal abscess caused by gram negative pathogens, possibly Proteus mirabilis, that resolved with medical treatment. The infection was secondary to a purulent infection in the patient's left knee. PMID- 1867510 TI - [Polyorchism: a case report]. AB - A case of polyorchism is described and the literature reviewed, highlighting the rarity of this pathological condition. To our knowledge, only 70 cases have been reported in the world literature. Similarly, Nocks' embryological development theory is discussed herein. The present case was diagnosed intraoperatively. No further studies were warranted since the intraoperative findings were compatible with a more common pathological condition. Furthermore, the malformation was asymptomatic and was not associated with any other scrotal conditions, unlike most of the cases described in the literature. We discuss the therapeutic approach and underscore the need to remove the supernumerary testis encountered intraoperatively when the continuity of the seminal duct is uncompromised. PMID- 1867512 TI - [Spontaneous perirenal hematoma. Report of 2 cases]. AB - We report on two cases of spontaneous perirenal hematoma secondary to ruptured angiomyolipoma in a patient with tuberous sclerosis and another patient with a simple renal cyst. The diagnostic and therapeutic aspects of this rare disease entity are discussed. PMID- 1867513 TI - [Chilaiditi syndrome in the differential diagnosis of renal colic]. AB - We report on a case of hepatodiaphragmatic interposition of the colon in a 45 year-old patient who presented at the emergency department with a clinical picture of renal colic. When making the differential diagnosis, we should take into account that the clinical picture known as Chilaiditi syndrome may mimic renal colic. PMID- 1867514 TI - [Hematoma of the iliac psoas secondary to anticoagulant treatment. Urological implications]. AB - We describe the urological manifestations arising from hematoma of the left iliac psoas that developed in the course of anticoagulant therapy in a 54-year-old patient with a mitral prosthesis. The onset of the clinical picture was acute and mimicked left reno-ureteral colic. Ultrasound and CT were decisive in making the diagnosis, revealing a left retroperitoneal mass in the anterolateral aspect of the left psoas muscle. Intravenous urography evidenced the urological repercussions of the disease process consisting of medialization of the left ureter, ureterohydronephrosis, and anterior and lateral displacement of the kidney. Although this condition is considered by most to be a surgical emergency, we opted for conservative treatment because the patient had no hemodynamic instability, severe obstructive uropathy or signs or crural paralysis. The literature on the urological repercussions of psoas hematomas due to anticoagulant therapy is briefly reviewed. PMID- 1867515 TI - [Fever and leukemoid reaction in bladder cancer: report of a case]. AB - The authors present a unique case of bladder cancer that presented as paraneoplastic syndrome of fever and leukemoid reaction. Furthermore, the patient had a left renal tumor histologically similar to the bladder tumor. We discuss whether the foregoing was a metastatic or a primary tumor coexisting with a bladder tumor. The neoplastic syndromes affecting patients with bladder neoplasms are briefly discussed. PMID- 1867516 TI - Free fibrous pseudotumor: an exceptional appearance. AB - We present a case of free fibrous pseudotumor in left hydrocele in a 42-year-old man. The patient was submitted to a scrotomy exploration and the course of the disease was benign. PMID- 1867518 TI - Radiolabeled antibody imaging in the management of colorectal cancer. Results of a multicenter clinical study. AB - Presurgical colorectal cancer patients (n = 116) received single intravenous infusions of 1 mg of CYT-103 (OncoScint CR103), an immunoconjugate of monoclonal antibody B72.3, radiolabeled with 111In. Following gamma camera imaging, 103 patients underwent an operative procedure: 92 had primary or recurrent colorectal carcinoma, 1 patient evaluated for recurrence of colorectal cancer had a second primary malignancy (small cell lung), and 10 patients had no demonstrable evidence of malignancy. 111In-CYT-103 immunoscintigraphic findings were consistent with the pathologic diagnoses for 70% of patients with colorectal cancer and 90% of disease-free patients. Antibody imaging contributed to surgical decision making through the detection of occult disease (12% of patients) and the confirmation of localized, potentially resectable disease without regional or metastatic spread. Seven patients (6%) experienced adverse effects, primarily fevers and itching, and 33% of patients developed antibodies to murine immunoglobulin after administration of 111In-CYT-103. The results of this study suggest that 111In-CYT-103 is a useful diagnostic tool for the presurgical evaluation of colorectal cancer patients. PMID- 1867517 TI - The influence of intraoperative hypotension and perioperative blood transfusion on disease-free survival in patients with complete resection of colorectal liver metastases. AB - An increased interest in surgical treatment of liver metastases from colorectal origin has evolved recently. However not all patients benefit from this approach, with early recurrence and death still being encountered. To evaluate clinical as well as perioperative factors that might significantly affect the outcome of patients with completely resected colorectal liver metastases, we examined 116 patients who underwent resection between September 1987 and August 1989. Median follow-up time was 13.2 months (0.6 to 31.4 months). The overall survival rate was 91% at 1 year and 75% at 2 years. Median survival was not reached. Median disease-free survival time was 11.5 months, with 49.4% and 21.2% of the patients being free of disease at 1 and 2 years, respectively. By univariate analysis, site of primary colorectal cancer, preoperative carcinoembryonic antigen (CEA) level, size of metastases, number of metastases, length of operation time, percentage mean arterial pressure, number of hypotensive episodes, duration of hypotensive episodes, and whole blood transfusion significantly affected recurrence rate following resection. However only site of primary tumor, CEA, number of metastases, and number of hypotensive episodes remained significant in the multivariate analysis. The most significant single factor that affected recurrence rate was the number of hypotensive episodes during the operative procedure. It is concluded that hypotensive episodes, even when well controlled, should be avoided during operation to maximize the chances of cure and prolong disease-free survival of patients with colorectal liver metastases. PMID- 1867519 TI - The prognosis of melanoma patients with metastases to two or more lymph node areas. AB - The prognosis of melanoma patients who present with metastatic involvement of two or more noncontiguous lymph node regions before the detection of extranodal metastases has not been previously reported. We identified 21 patients with metastatic melanoma in at least two nodal basins in a review of 175 patients with melanoma undergoing lymphadenectomy at the National Cancer Institute. The median survival time of these patients was 46 months, with 55%, 27%, and 17% of the patients alive 2, 5, and 10 years, respectively, after the second lymphadenectomy. Because the prognosis of melanoma patients with metastases to two or more regional nodal areas appears equivalent to that of patients with metastatic involvement of only one regional node site, lymphadenectomy of the involved groups should be performed with therapeutically curative intent. PMID- 1867520 TI - Metabolic consequences of (regional) total pancreatectomy. AB - Little information has been reported on the metabolic characteristics of the totally pancreatectomized patient or the efficacy of medical management after radical pancreatic surgery. The prospective evaluation of 49 such patients, with 31% followed for 48 or more months, forms the basis of this report. The major immediate postoperative challenge is control of diarrhea and weight stabilization. Chronically patients have an increased daily caloric requirement (mean +/- SE, 56 +/- 1 kcal/kg), not wholly explained by moderate steatorrhea (fecal fat excretion, 16% +/- 2% of unrestricted fat intake). Despite persistent malabsorption, deficiencies in fat-soluble vitamin, magnesium, and trace element serum levels can be prevented in most patients. Pancreatogenic diabetes is characterized by (1) absence of the major glucoregulatory hormones insulin and glucagon, (2) instability, and (3) frequent hypoglycemia, with the latter parameters improving with rigorous home glucose monitoring. No patient has developed clinically overt diabetic micro- or macrovascular disease. Performance status in long-term survivors has been reasonable. However adverse chronic sequelae of the operation occur and include an unusual frequency of liver disease, characterized by accelerated fatty infiltration, and osteopenia, with an 18% reduction in radial bone mineral content noted in pancreatectomized patients studied more than 5 years after surgery. PMID- 1867521 TI - The complex pattern of cytokines in sepsis. Association between prostaglandins, cachectin, and interleukins. AB - Although the cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) are important mediators of hemodynamic, metabolic, and immunologic alterations in the host during sepsis, it is not known whether there is any association between the release of these cytokines and prostanoids during sepsis. Sepsis induced by cecal ligation and puncture in rats led to a persistent elevation (p less than 0.05) of plasma TNF until 10 hours, steadily increasing (p less than 0.05) IL-1 plasma levels, and enhanced (p less than 0.05) IL-6 plasma levels at all time points compared to the sham group. Prostaglandin E2 plasma levels were elevated (p less than 0.05) at 5 hours (153 +/- 29 pg/mL; control: 47 +/- 11 pg/mL) and 10 hours (96 +/- 16 pg/mL; control: 21 +/- 5 pg/mL). Prostaglandin E2 production by splenic macrophages (sM phi) from septic animals was increased (p less than 0.05) at 5 hours (9.1 +/- 2.2 ng/mL) and 10 hours (5.6 +/- 1.5 ng/mL) compared to controls (3.3 +/- 0.3 ng/mL at 5 hours; 1.3 +/- 1.3 ng/mL at 10 hours). Incubation of sM phi from septic animals with ibuprofen enhanced (p less than 0.05) IL-1 and TNF synthesis, while IL-6 production was reduced (p less than 0.05). These results indicate that the alterations in prostanoid release and elevated plasma prostanoids may regulate the release and consequently the circulating levels of cytokines during sepsis. PMID- 1867522 TI - Lovastatin inhibits gallstone formation in the cholesterol-fed prairie dog. AB - The efficacy of lovastatin, an inhibitor of hepatic cholesterol synthesis in the prevention of cholesterol gallstone formation, was evaluated in the prairie dog model. Two groups of animals were maintained on either nonlithogenic or 1.2% cholesterol-enriched chow for 21 days. Seven of the animals in each group received lovastatin, and the remaining six received only distilled water. All of the cholesterol-fed/water-treated animals had crystals and 83% had gallstones, but none of the cholesterol-fed/lovastatin-treated animals had gallstones and only three had microscopic crystals. These data indicate that lovastatin inhibits cholesterol gallstone formation in a diet-induced model of gallstone disease. PMID- 1867523 TI - Dose response of fish oil versus safflower oil on graft arteriosclerosis in rabbit heterotopic cardiac allografts. AB - With the advent of cyclosporin A, accelerated coronary arteriosclerosis has become the major impediment to the long-term survival of heart transplant recipients. Due to epidemiologic reports suggesting a salutary effect of fish oil, the dose response of fish oil on graft coronary arteriosclerosis in a rabbit heterotopic cardiac allograft model was assessed using safflower oil as a caloric control. Seven groups of New Zealand White rabbits (n = 10/group) received heterotropic heart transplants from Dutch-Belted donors and were immunosuppressed with low-dose cyclosporin A (7.5 mg/kg/day). Group 1 animals were fed a normal diet and served as control. Group 2, 3, and 4 animals received a daily supplement of low- (0.25 mL/kg/day), medium- (0.75 mL/kg/day), and high- (1.5 mL/kg/day) dose fish oil (116 mg n-3 polyunsaturated fatty acid/mL), respectively. Group 5, 6, and 7 animals were supplemented with equivalent dose of safflower oil (i.e., 0.25, 0.75, and 1.5 mL/kg/day). Oil-supplemented rabbits were pretreated for 3 weeks before transplantation and maintained on the same diet for 6 weeks after operation. The extent of graft coronary arteriosclerosis was quantified using computer-assisted, morphometric planimetry. When the animals were killed, cyclosporin A was associated with elevated plasma total cholesterol and triglyceride levels in the control group. While safflower oil prevented the increase in plasma lipids at all dosages, fish oil ameliorated the cyclosporin induced increase in total cholesterol only with high doses. Compared to control animals, there was a trend for more graft vessel disease with increasing fish oil dose, as assessed by mean luminal occlusion and intimal thickness. A steeper trend was observed for increasing doses of safflower oil; compared to the high dose safflower oil group, animals supplemented with low-dose safflower oil had less mean luminal occlusion (16.3% +/- 5.9% versus 41.4% +/- 7.6%, p less than 0.017) and intimal thickness (7.9 +/- 1.9 microns versus 34.0 +/- 13.0 microns, analysis of variance: p = 0.054). Low-dose safflower oil also had a slight, but nonsignificant, beneficial effect on graft vessel disease when compared to control rabbits. The same trends were observed in the degree of histologic rejection (0 = none to 3 = severe) in fish oil- and safflower oil-treated animals. Rejection score correlated weakly but significantly (p = 0.0001) with mean luminal occlusion (r = 0.52) and intimal thickness (r = 0.46). Therefore allograft coronary disease in this model appeared to exhibit an unfavorable, direct-dose response to fish oil and safflower oil, independent of effects on plasma lipids.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1867526 TI - Intrathoracic cardiac prosthesis: is it really not clinically acceptable? PMID- 1867525 TI - The biology of acute transplant rejection. AB - An intriguing and increasingly understood facet of immune responses is the ability of a recipient to destroy a foreign tissue or organ graft. The phenomenon of acute rejection of an allograft involves a series of complex and inter-related cellular and humoral events, culminating in graft death. Some of the current thinking surrounding this phenomenon is reviewed. PMID- 1867527 TI - Development of a new antithrombogenic continuous ultrafiltration system. AB - By interfacing a polyacrylonitrile (PAN)-polyethyleneoxide (PEO) membrane with an ionically heparin-bound catheter, tubing, and module header, a totally antithrombogenic continuous ultrafiltration system (ACUS) was developed and its performance, persistent antithrombogenicity, and well-maintained ultrafiltration level were confirmed through animal experiments. Although the amount of heparin released and accumulated in vitro from those heparinized parts was very low and stable (on the order of 1 x 10(-2) U/cm2/min), partial thromboplastin time evaluated in vivo was not elongated during passage through the ACUS. Extracorporeal circulation time with the ACUS in unheparinized dog model was 458 +/- 302 min (n = 24), whereas those of partially modified (antithrombogenic) system did not exceed 100 min. As compared with that in a conventional continuous arteriovenous hemofiltration system, an extracorporeal circulation with the ACUS in an unheparinized dog model revealed significantly less fluctuation of platelet count, and no adherent platelets were observed on the surface of the PAN-PEO membrane. An ACUS consisting of a PAN-PEO membrane and heparinized parts was thus demonstrated to have good platelet compatibility. An ACUS with a surface area of 0.25 m2 was applied to two patients with acute renal failure. Hemofiltration without systemic heparinization lasted for 44 h per hemofilter, and a stable level of ultrafiltration was maintained. This system seems to be applicable for the clinical management of volume overload, especially in patients with bleeding tendencies or postoperative bleeding. PMID- 1867524 TI - Interleukin-2 induces early multisystem organ edema mediated by neutrophils. AB - Interleukin-2 (IL-2), an agent known to activate neutrophils (PMN) with thromboxane (Tx)B2 release, produces pulmonary edema within 6 hours of intravenous infusion. This study tests the role of PMN in mediating the edema. Anesthetized rats received 10(6)U recombinant human IL-2 (n = 15) or vehicle (n = 14) as a constant intravenous infusion during a period of 1 hour. At this time there was leukopenia 3.63 +/- 0.43 (x10(3)/mm3) relative to vehicle-infused control rats 6.12 +/- 0.86 and a decline in PMN, 2.19 +/- 0.14 relative to control value of 3.33 +/- 0.05 (both p less than 0.05). After 6 hours edema, as measured by increase in the wet to dry weight (W/d) ratio, was present in the lungs (4.93 +/- 0.20 relative to control 4.06 +/- 0.10), heart (4.09 +/- 0.11 versus 3.76 +/- 0.08), liver (3.50 +/- 0.10 versus 3.18 +/- 0.10), and kidney (4.25 +/- 0.07 versus 4.00 +/- 0.07) (all p less than 0.05). There was increased lung permeability demonstrated by bronchoalveolar lavage fluid protein concentration of 1970 +/- 210 micrograms/mL relative to control 460 +/- 90 micrograms/mL (p less than 0.05). Interleukin-2 resulted in lung PMN sequestration of 53 +/- 7 PMN/10 high-power fields (HPF) relative to 23 +/- 2 PMN/10 HPF in controls (p less than 0.05) and increased plasma TxB2 levels to 1290 +/- 245 pg/mL relative to control 481 +/- 93 pg/mL (p less than 0.05). Pretreatment of other rats (n = 8) with selective anti-rat neutrophil antiserum 18 hours before the experiment led to a peripheral PMN count 10% of baseline and prevented edema in the lungs (W/d ratio 4.20 +/- 0.16) and heart (3.67 +/- 0.07) (both p less than 0.05) but not liver or kidney. Protein in lung lavage was reduced to 760 +/- 220 micrograms/mL (p less than 0.05). The protection afforded by leukopenia was associated with lack of PMN sequestration and prevention of the increase in plasma Tx levels (484 +/- 120 pg/mL, p less than 0.05). These data indicate that the rapid induction of lung and heart edema with a 1-hour infusion of IL-2 in the rat is mediated, in large part, by activated PMNs. PMID- 1867528 TI - Evaluation of a filtration lymphocytapheresis (LCP) device for use in the treatment of patients with rheumatoid arthritis. AB - A practical on-line lymphocytapheresis (LCP) system using a leukapheresis filter (Cellsorba, Asahi Medical Co.) was evaluated in six patients with refractory rheumatoid arthritis. This filter consists of nonwoven fine polyester fiber wound around a porous cylinder. The blood was passed through the polyester fiber at a flow rate of 50 ml/min for 60 min. LCP was carried out once a week in the first month and biweekly in the next 2 months. An average of 98% of the leukocytes that entered the filter (1.27 x 10(10) cells) and 100% of the lymphocytes that entered the filter (3.66 x 10(9) cells) were removed in the first LCP. A total of 96.6% of the platelets and 2.7% of the erythrocytes that entered the filter were also removed. All of the patients showed clinical improvement in morning stiffness, Lansbury articular index, and functional capacity, with no adverse reaction. The number of circulating erythrocytes and platelets and the concentration of various serum components showed no significant change during the treatments. This LCP system required no fresh frozen plasma, albumin, or other blood transfusion. The number of circulating lymphocytes decreased to 65-70% of the pretreatment circulating lymphocyte count at the last procedure, with a decrease in the ratio of Leu3a positive cells to Leu2a positive cells. The proliferative response to phytohemagglutinin and concanavalin A was improved. These data suggest that LCP to remove approximately 3 x 10(9) lymphocytes once a week or biweekly has an immunomodulatory effect. PMID- 1867529 TI - Bioartificial liver using hepatocytes on biosilon microcarriers: treatment of chemically induced acute hepatic failure in rats. AB - An artificial liver support procedure based on hemoperfusion via hepatocytes cultured on microcarriers is described. The efficiency of the system was assessed by the survival rate of rats treated with either lethal dosage of 7% CCl4 [30 ml/kg body weight (b.w.)] or D-galactosamine (2.5 g/kg b.w.). In CCl4-treated rats, hemoperfusion via empty microcarriers (n = 16) revealed no surviving animals, whereas the use of the bioartificial liver (n = 11) resulted in 80% (p less than 0.01) and 60% (p less than 0.05) survival 48 and 168 h after hepatotoxin, respectively. For the same time periods, the survival rate in D galactosamine-intoxicated rats after hemoperfusion with hepatocytes (n = 20) was approximately 60% (p less than 0.05) and was only 5% in those of rats treated with empty microcarriers (n = 20). Sublethal dosage of 7% CCl4 (15 ml/kg b.w.) caused 25% mortality and prolonged (48 h) increase of activity of the liver enzymes and bilirubin levels in the serum of surviving animals. In these rats (n = 8) at the end of 3 h of hemoperfusion via hepatocytes, the bilirubin concentration decreased by 45% as compared with the control group (n = 6) treated with empty microcarriers. Moreover, by 48 h after intoxication, the use of the bioartificial liver resulted in more than a three-fold decrease in glutamate oxaloacetate transaminase and a 10-fold decrease in glutamate-pyruvate transaminase serum activity as well as a fivefold decline in total and a ninefold decline in conjugated bilirubin levels as compared with the control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867530 TI - Influence of antihypertensive drugs and steroid hormones on protein adsorption/desorption on polycarbonate. AB - To develop artificial materials for prolonged use in the vascular system, the complicated process of surface-induced thrombosis needs to be better understood. It is documented that certain antihypertensive drugs can inhibit platelet adhesion to an artificial surface; on the other hand, steroid drugs increase platelet surface attachment to variable degrees. This study demonstrates the changes in protein-surface binding with certain antihypertensive and antianginal drugs--namely, digoxin, sorbitrate, thyroxine, sembrina and hydralazine--and five steroid hormones--estrone, progesterone, beta-estradiol, 7(OH) progesterone, and testosterone--using trace labelling methods. It seems that the addition of these antihypertensive drugs to the polymer-protein system has increased the level of surface-bound albumin and reduced the fibrinogen surface concentration to variable degrees. A reversed pattern of protein-surface attachment has been evident with steroid hormones. Thus, it appears that the changes in platelet attachment due to various drugs may be dependent on the availability of fibrinogen receptors at the polymer interface, along with other possible biological factors. Prolonged use of antihypertensive drugs may not have any significant side effect for patients having an implant. However, the use of steroids or steroid-containing oral contraceptive agents may not be advisable for patients having an artificial implant in contact with blood. A better understanding of the mechanism of these drugs under in vivo conditions is needed to correlate these findings. PMID- 1867531 TI - Long-term respiratory assistance using a right ventricular assist device system and a membrane oxygenator. AB - A new method for long-term respiratory assistance using a right ventricular assist device (RVAD) system and a membrane oxygenator (MO) was designed and evaluated. An air-driven RVAD was implanted between the right atrium and the pulmonary artery in five goats and an MO was set on the outlet conduit of the RVAD 2 weeks postoperatively. Two types of MOs [the SciMed (Life Systems) silicone sheet MO and a prototype MO using a novel multilayered composite membrane] were used in this study. Respiratory support with this system under systemic heparinization could be conducted for 4-8 days without major problems accompanied with conventional extracorporeal membrane oxygenation (ECMO) such as surgical bleeding, destruction of the blood components, serum leakage, insufficient bypass flow, and fatal systemic thrombosis. This method opened the possibility for ECMO to be used as a bridge before lung or heart-lung transplantation. PMID- 1867532 TI - Local blood residence times in the Penn State artificial heart. AB - Thrombus formation associated with cardiac assist devices is a major concern in their application. Thrombogenesis is thought to be a function of, among other things, fluid shear stress and blood residence time. In the current study, a fiber-optic probe was developed and employed in conjunction with indicator dilution techniques to evaluate the local near-wall fluid residence times at a number of locations inside the Penn State 70 cc parallel port and 100 cc angle port left ventricular assist devices (LVADs). In this in vitro study, both 50% and 30% systolic duration regimes were investigated for each chamber. Using a relatively inexpensive optical arrangement, two decades of dye concentration (10( 6)-10(-4) M of fluorescein sodium) were easily discernible. The washout process was characterized by an exponential decay with a time constant tau. For all positions and operating conditions tested, tau values were between 1-2 beats. In all cases tested, values of tau in the valve regions were significantly longer (8.9-31.6%; p less than or equal to 0.0075) than in the chamber proper. At every position tau was substantially lower in the 70 cc chamber than in the larger pump (17.8-27.4%). Systolic duration appeared to have no significant effect on tau at the majority of investigated sites. The results indicate that the valve regions, which are known to have greater shear stresses, are also in contact with a volume element of blood for a longer time than is the rest of the chamber. This combination may be detrimental to fragile blood components. PMID- 1867534 TI - Changes of serum bilirubin fraction in postoperative liver failure cases treated by plasmapheresis: an effective marker for evaluation of bilirubin removal. AB - Utility of a new method of bilirubin fractionation was evaluated in monitoring the effectiveness of plasma exchange (PE) performed in 10 postoperative cases with liver failure. Fractionation of serum bilirubin by high-performance liquid chromatography demonstrated a higher delta bilirubin (B delta) peak against lower conjugated bilirubin peaks [monoconjugated bilirubin (MCB) and diconjugated bilirubin (DCB)] in the three recovered cases. The calculated ratio of MCB/B delta and the ratio of B delta/(MCB + DCB + B delta) in the recovered cases showed statistically significant different against seven unrecovered cases (p less than 0.01). These results suggest that the recovered cases had a different quality hyperbilirubinemia and a different disease entity before PE as well as a different response to PE, and this novel method for serum bilirubin subfraction is considered a useful marker in selecting a patient responsive to PE. PMID- 1867533 TI - The soft-shell mushroom heart remembered. PMID- 1867535 TI - Quality control of hemoglobin solutions. I. The purity of hemoglobin before modification. AB - It is not yet clear whether the toxicity of hemoglobin solutions is due to hemoglobin per se, contaminants, or both. To elucidate the problem, it is first necessary to prepare "pure hemoglobin," i.e., hemoglobin completely free of (a) bacterial endotoxins, (b) phospholipids of the red cell membrane, and (c) other proteins and/or peptides. The methods found most sensitive in the determination of such purity are here presented. Consensus on the adoption of these methods and on the meaning of the term "purity" would help to achieve (a) a better understanding of the toxicity problem, (b) a more meaningful exchange of information among investigators and (c) the ultimate development of nontoxic solutions. PMID- 1867537 TI - Risk to the treating ophthalmologist when using the laser. PMID- 1867536 TI - Hepatic venous oxygen saturation monitoring in patients with assisted circulation for severe cardiac failure. AB - In order to assess the adequacy of hepatic perfusion, hepatic venous oxygen saturation (ShvO2) was monitored in five patients undergoing mechanical circulatory support. Two patients were with intra-aortic balloon pumping (IABP), one was with a left ventricular assist device (LVAD), and two were with biventricular assist devices (BVAD). The mean ShvO2 values during assistance in each patient ranged from 27 to 84%. One patient with IABP showed persistently low ShvO2 (less than 30%) in spite of higher mixed venous oxygen saturation (SvO2) and subsequently developed hepatic dysfunction and multiple organ failure. In another patient, ShvO2 was 22% on average during LVAD, but increased to greater than 50% after adding a right ventricular assist device (RVAD). Of 3 patients with persistently high ShvO2 (44-80%, on average), only one developed hepatic failure--probably from prior severe shock--and the other two did not develop hepatic failure. There was a significant negative correlation between ShvO2 and splanchnic excess lactate, the parameter of anaerobic metabolism in the splanchnic area. In contrast, there was no correlation between simultaneously measured ShvO2 and SvO2 values when analyzed in a range of SvO2 below 70%. ShvO2 monitoring may be useful for evaluation of hepatic perfusion status in the management of critical patients, requiring assisted circulation. PMID- 1867538 TI - Posterior precortical vitreous pocket. PMID- 1867539 TI - Endophthalmitis vitrectomy study. PMID- 1867540 TI - Persistent hyperplastic primary vitreous with glaucoma presenting in infancy. PMID- 1867542 TI - Retinal and optic nerve manifestations of autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy. PMID- 1867541 TI - Mycobacterium gordonae keratitis after penetrating keratoplasty. PMID- 1867543 TI - Choroidal folds and dural cavernous sinus fistula. PMID- 1867544 TI - RBRVS cuts ophthalmologists' Medicare fees by 35%. PMID- 1867545 TI - Calcific band keratopathy. PMID- 1867546 TI - The 75th anniversary of the American Board of Ophthalmology. PMID- 1867547 TI - Outcomes of eye care from Medicare data. PMID- 1867548 TI - Endogenous Candida endophthalmitis after intravenous anesthesia with propofol. AB - Propofol is an intravenous anesthetic agent that was approved by the US Food and Drug Administration in October 1989. It has gained rapid acceptance and is in widespread use. In June 1990, the Centers for Disease Control reported four clusters of postsurgical infections associated with the use of propofol. We describe one of those clusters, consisting of four cases of endogenous Candida albicans endophthalmitis. These infections occurred in nonimmunocompromised patients after they had undergone nonophthalmologic surgery in which propofol had been used as anesthesia. An investigation by the Centers for Disease Control concluded that the infections in these patients were due to extrinsic contamination of propofol during preparation for use at the hospital. Ophthalmologists should be aware of this new potential source of endogenous endophthalmitis. PMID- 1867550 TI - Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey. AB - A detailed ocular examination, including perimetry, was conducted on 5308 black and white subjects aged 40 years and older in a population-based prevalence survey in east Baltimore, Md. Repeated, detailed examinations were carried out on selected subjects. Roughly half of all subjects with optic nerve damage from primary open angle glaucoma, regardless of race, were unaware that they had the condition. The average intraocular pressure (IOP) among black patients with glaucoma who were receiving treatment was virtually identical to that in those black patients who were not receiving treatment (median IOP, 20 mm Hg); treated eyes of white patients had a lower IOP than those eyes of white patients who were not receiving treatment (mean [+/- SD] IOP, 18.69 +/- 3.23 mm Hg vs 24.15 +/- 5.23 mm Hg; P less than .001). The risk of glaucomatous optic nerve damage increased with the height of the screening IOP, particularly at levels of 22 to 29 and 30 mm Hg and above (relative rate compared with IOP of 15 mm Hg or lower, 12.8 and 40.1 mm Hg, respectively). More than half of all glaucomatous eyes had a screening IOP below 21 mm Hg, whether these eyes were receiving treatment or not. The IOP in glaucomatous eyes tended to rise on follow-up, in contrast with nonglaucomatous eyes in which the IOP was as likely to rise as to fall. Results confirmed that IOP is an important factor in glaucoma, but did not support the traditional distinction between "normal" and "elevated" pressure, nor its corollaries, "low-tension" glaucoma and "high-tension" glaucoma. PMID- 1867549 TI - National outcomes of cataract extraction. Endophthalmitis following inpatient surgery. AB - We analyzed the likelihood of rehospitalization for endophthalmitis in 338,141 Medicare beneficiaries over age 65 years who were admitted to US hospitals for cataract extraction in 1984. This cohort represents approximately one half of all persons who underwent cataract extraction under the Medicare program in 1984. Extracapsular extraction was performed in 195,587 (58%) of cases, intracapsular cataract extraction in 99,971 (30%), and phacoemulsification in 28,474 (8%). The risk of rehospitalization for endophthalmitis in the year following surgery was 0.17% for intracapsular cataract extraction compared with 0.12% for extracapsular extraction or phacoemulsification (P less than .002). The risk of endophthalmitis at 1 month was higher for intracapsular cataract extraction than for extracapsular extraction or phacoemulsification (0.11% vs 0.085%), although the difference did not reach statistical significance. Cataract surgery accompanied by anterior vitrectomy increased the 1-month risk of rehospitalization for endophthalmitis to 0.41%, more than a four-fold increase over that for cataract surgery alone (0.09%; P less than .05). The rates of endophthalmitis at 1 year were 0.58% and 0.13%, respectively, for cataract surgery with anterior vitrectomy and cataract surgery alone (P less than .0001). No significant differences in the rate of rehospitalization for endophthalmitis were observed based on the use of an intraocular lens, age, or race. Endophthalmitis within 1 year of surgery was 1.2 times more frequent in men than in women (0.16% vs 0.13%; P = .03). Overall, the likelihood of postoperative endophthalmitis from a national sample is consistent with case series previously reported. PMID- 1867551 TI - Exercise training reduces intraocular pressure among subjects suspected of having glaucoma. AB - The effect of exercise conditioning on elevated intraocular pressure has not been previously described among sedentary individuals. We prospectively observed intraocular pressure for nine sedentary subjects suspected of having glaucoma before and after 3 months of aerobic exercise training. Mean (+/- SEM) aerobic capacity, as assessed by maximal oxygen uptake, increased 6.3 +/- 1.6 mL.kg-1.min 1 (30%) (P less than .02). Mean intraocular pressure decreased 4.6 +/- 0.4 mmHg (20%) (P less than .001) at the end of the conditioning period. With cessation of exercise and subsequent detraining, intraocular pressure returned to elevated preconditioning levels by 3 weeks. Regular aerobic exercise is associated with a reduction in elevated intraocular pressure and may represent an effective nonpharmacologic intervention for patients suspected of having glaucoma. PMID- 1867552 TI - A simple method of determining the time course of timolol's effects on aqueous flow in humans. AB - We have devised a simple method of determining the time course of the effects of timolol maleate on aqueous flow using changes in aqueous protein concentrations. Aqueous protein concentrations were measured with a laser flare-cell meter. First, the value of the coefficient of protein entry into the anterior chamber (kin) was determined in both eyes of 10 normal subjects. One week later, aqueous protein concentration changes were measured in both eyes of the same subjects before and after instillation of timolol in one eye. From these changes and the value of kin, changes in the aqueous flow rate were calculated using an equation formulating protein kinetics in the anterior chamber. Results of a separate experiment showed that instillation of topical timolol did not change the kin, justifying use of the kin as determined without considering timolol in the calculation. The calculated flow rate had a maximum decrease of 30% +/- 10% (mean +/- SEM, n = 10) 4 hours after instillation in treated eyes and of 10% +/- 6% 3 hours after instillation in fellow, untreated eyes. PMID- 1867553 TI - Mizuo phenomenon in X-linked retinoschisis. Pathogenesis of the Mizuo phenomenon. AB - Four unrelated males with X-linked retinoschisis and a golden fundus reflex had Mizuo-Nakamura phenomenon, which, to our knowledge, has been described only in Oguchi's disease and X-linked cone dystrophy. These findings, together with experimental observations and data from the literature, led us to hypothesize that the Mizuo-Nakamura phenomenon is caused by an excess of extracellular potassium in the retina as a result of a decreased potassium scavenging capacity of retinal Muller cells. PMID- 1867554 TI - Retinal thickness analysis for quantitative assessment of diabetic macular edema. AB - Diabetic macular edema is a major cause of vision loss and is evaluated with qualitative or semiquantitative techniques. A new quantitative method for assessment of macular edema using retinal thickness analysis was applied to 19 patients with diabetic macular edema. Foveal thickening was frequently coupled with poor visual acuity. Slit-lamp biomicroscopy and stereophotography detected 80% and 78% of local areas of thickening, respectively, but failed to detect locations with average thicknesses of 1.5 and 1.6 times normal, respectively. Fluorescein leakage on angiography was generally associated with retinal thickening, but locations with similar degrees of leakage had widely varying retinal thickening. Fluorescein leakage in the posterior vitreous correlated poorly with the degree of foveal thickening. These results indicate that quantitative measurement of retinal thickness may become useful in the management of diabetic patients with macular edema. PMID- 1867555 TI - Congenital optic tract syndrome. AB - We describe two patients with complete homonymous hemianopia who were unaware of their visual field defects. The clinical impression of an optic tract syndrome was confirmed by magnetic resonance imaging, which showed absence of the corresponding tract in each case. The pathogenesis of congenital absence of the optic tract is unclear but it could represent either a primary failure of development or secondary atrophy due to focal injury during the perinatal period. PMID- 1867556 TI - Electroretinographic monitoring of retinal function during eye surgery. AB - We performed a pilot study of electroretinographic monitoring of retinal function during eye surgery performed with local anesthesia. A contact lens with a built in light-emitting diode was sterilized and used as both a stimulus source and a recording electrode for 30-Hz flicker electroretinograms. Each recording required 7 seconds, during which the operating light (but not the room light) was switched off. Electroretinograms recorded during surgery on 10 patients with minimal retinal abnormality were evaluated for the effects of light adaptation caused by regular exposure to an operating light source or operating microscope. The fluctuations of the amplitude and peak time were small, indicating that this technique can be used to monitor retinal function during eye surgery. Some results during retinal and vitreous surgeries are shown. PMID- 1867557 TI - Effect of temperature on electroretinograph readings during closed vitrectomy in humans. AB - To determine whether intraocular cooling using room-temperature irrigating solution can cause abnormal electroretinograph readings, we operated on six patients with premacular fibrosis and minimal retinal detachment, measuring the temperature in the vitreous cavity and using an electroretinographic monitor. The temperature in the vitreous cavity dropped to 27 degrees C to 28 degrees C after vitrectomies during which room-temperature solutions were used. This resulted in abnormal electroretinograph readings (markedly delayed peak times and reduced amplitudes). These results suggest that the routinely used room-temperature solution affects retinal function during vitrectomy; however, this functional change was reversible in patients having only minimal retinal abnormality. PMID- 1867558 TI - Corneal choristoma with microphthalmos. AB - We report two rare cases of corneal choristoma with microphthalmos. In both cases, the whole thickness of the cornea, as well as the anterior chamber and iris, was replaced by cutaneous and subcutaneous tissue. In case 1, diagnosed as dermoid choristoma, the cutaneous tissue contained skin appendages and subcutaneous fibrofatty tissue extended into the vitreous cavity. The fibrous mass in the cavity contained fragments of retina. In case 2, diagnosed as a dermislike choristoma, the cutaneous tissue lacked skin appendages. These choristomatous cutaneous tissues hindered normal growth of ocular structures, resulting in microphthalmos. Use of computed tomography was helpful in evaluating the extent of ocular tissue involvement and accompanying intraocular malformations. PMID- 1867560 TI - Superior oblique adjustable suture surgery. A rabbit model. AB - Adjustable suture techniques have played a limited role in superior oblique muscle surgery. In this study, one of two different adjustable suture techniques was performed on the superior oblique muscle of 12 rabbit eyes. One day after surgery, each muscle was advanced using the adjustable suture and was permanently secured to the eye. No significant difference was noted in the amount of force (P = .4603) necessary to advance the muscle with either of the procedures. Postmortem examinations performed several weeks after both procedures demonstrated that the superior oblique muscle was firmly attached to the globe in the same position where it was left following the adjustment. Adjustable suture techniques may be useful alternatives to traditional superior oblique muscle surgery. PMID- 1867559 TI - Retinal artery obstruction and atheromas associated with non-Hodgkin's large cell lymphoma (reticulum cell sarcoma). AB - A 71-year-old woman developed branch retinal artery obstruction as the presenting manifestation of a large cell non-Hodgkin's lymphoma. Multifocal chorioretinal scars were present in the same eye. She experienced progressive visual loss accompanied by development of multiple yellow retinal arterial wall plaques, extension of retinal opacification into other quadrants, and increasing vitreous cellular infiltration. Clinical diagnoses included branch retinal arterial obstruction caused by toxoplasmosis retinitis, multifocal choroiditis and panuveitis simulating the presumed ocular histoplasmosis syndrome, vitiliginous chorioretinitis, and the acute retinal necrosis syndrome. Four months after onset, the right eye was blind and was enucleated. Histopathologic examination revealed extensive lymphomatous infiltration and necrosis of the retina and optic nerve. The retinal arteries were partly obstructed by lymphomatous infiltration and atheromas. Subsequently, the left eye and central nervous system were involved by lymphoma. PMID- 1867561 TI - Comparative efficacies of soft contact lens disinfectant solutions against microbial films in lens cases. AB - Biofilms of Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus epidermidis, Streptococcus pyogenes, and Candida albicans, established in the wells of a polyethylene contact lens case, retained viability to certain soft contact lens disinfectant solutions after exposure for the manufacturer's minimum recommended disinfection times. The relative order of resistance of bacterial biofilms was as follows: S marcescens was greater than P aeruginosa, which was greater than S epidermidis, which was greater than S pyogenes. Air drying of biofilms for 10 hours increased the efficacy of the disinfectant solutions, but drying was not enough to decrease the incidence of recovery to 0% for all solutions. Hydrogen peroxide was more effective against biofilms than disinfectant solutions formulated with chlorhexidine gluconate or polyquaternium 1 or polyaminopropyl biguanide. We recommend that determination of efficacy of contact lens disinfectant solutions should include challenges against biofilms. PMID- 1867562 TI - Amelanotic malignant melanoma of the eyelid. PMID- 1867563 TI - A simple method of conjunctival dissection for Gunderson flaps. AB - In this study we describe a method for simplifying the often frustrating and time consuming task of dissecting conjunctiva from underlying Tenon's capsule during Gunderson flap procedures. Using gentian violet marks as a guide, a needle and two pairs of scissors are used in series to separate superior bulbar conjunctiva from the superficial layers of Tenon's capsule along a series of semimeridians. The techniques provides the surgeon with important landmarks, reduces the risk of inadvertent buttonholing, and minimizes conjunctival retraction caused by uneven dissection of Tenon's capsule. PMID- 1867564 TI - Instrumentation for superior cortex removal. AB - A recently developed aspiration tip and suction distributor for use in cataract surgery allow two-handed aspiration of the residual cortex lentis through the two incisions used in two-handed phacoemulsification. The instruments also facilitate removal of the cortex lentis at the 12 o'clock position, which is sometimes difficult to aspirate with an irrigation-aspiration tip only. PMID- 1867565 TI - [Proceedings report 1991 of the German Society for Otorhinolaryngology,Head and Neck Surgery. Part I. Partial resection of the larynx in neoplasms and otorhinolaryngologic diseases in children]. PMID- 1867566 TI - [Allergic manifestations in the ENT area in childhood]. PMID- 1867567 TI - [Laryngeal dissection with chordectomy and vertical laryngeal resection]. PMID- 1867568 TI - [Conservative surgical treatment of supraglottic cancer and lymph node metastases]. PMID- 1867569 TI - [Larynx and hypopharynx cancers--endoscopic surgery with laser: possibilities and limits]. PMID- 1867570 TI - [The three-quarters laryngectomy--personal experience, indications, surgical technique, results]. PMID- 1867571 TI - [Subtotal functional laryngectomy with cricohyoidopexy]. PMID- 1867572 TI - [Partial surgery in treatment of cancers of the piriform sinus and lateral epilarynx]. PMID- 1867574 TI - [Sinusitis in childhood]. PMID- 1867573 TI - [Secretory otitis media]. PMID- 1867575 TI - [Snoring and sleep-related respiratory disorders in children--clinical aspects, differential diagnoses and indications for adenotonsillectomy]. PMID- 1867576 TI - Uterine activity in dysfunctional labour and target uterine activity to be aimed with oxytocin titration. AB - Uterine activity was quantified using a transducer tipped intrauterine catheter in 75 nulliparous women with dysfunctional labour. The active contraction area profiles in these women were below the median levels reported for those who had normal progress of labour from our institution. When uterine activity was augmented with oxytocin, 90.7% progressed in labour and delivered vaginally. Six patients (8%) showed poor progress despite good uterine activity and had to be delivered by caesarean section (CS) for failure to progress and signs of cephalopelvic disproportion. The pre- and post-augmentation uterine activity were similar in those who delivered vaginally or by CS and was not helpful in identifying those who had cephalopelvic disproportion. Of the 75 women who had slow progress of labour, 50 had a contraction frequency of less than 1 in 3 min whilst 25 had a minimum frequency of 1 in 3 min or more. All except one in the latter group delivered vaginally when oxytocin was titrated to achieve a contraction frequency of 1 in 2 to 2 1/2 min which were clinically judged to be adequate based on a duration greater than 40 sec. Oxytocin should be titrated to achieve a target contraction frequency of 1 in 2 to 2 1/2 min lasting greater than 40 sec to achieve good obstetric outcome in those with dysfunctional labour. PMID- 1867577 TI - Clinicostatistical study of low potential malignancy ovarian cystadenoma (borderline cases). AB - The number of ovarian cystadenoma of low potential malignancy (abbreviation: LPM) was 31 (5.7%) among common epithelial tumors [benign cystadenoma = 400 (74.0%), carcinoma = 110 (20.3%)]. Their mean ages, bilaterlity, frequency of ascites and nulligravidity were situated intermediately between those of benign cystadenoma and carcinoma. Abdominal tumor, distention, pain and metromenorrhagia were the main symptoms, although gastrointestinal complaints were rare in LPM cystadenoma. With LPM cystadenoma, 19 (61.3%) patients were at stage I, 7 (22.6%) at stage II and 5 (16.1%) at stage III, but with carcinoma, 44 (40.0%) were at stage III-IV [33 (30.0%) at stage I, and 31 (28.2%) at stage II]. The 5-year actuarial survival rate was 90% for LPM cystadenoma, but 43% for carcinoma. These results suggest that the clinical and biological features as well as the histological definition of LPM cystadenoma are situated intermediately between those of benign cystadenoma and carcinoma. PMID- 1867578 TI - Prenatal diagnosis of rubella infection by fetal blood sampling. AB - Prenatal diagnosis of rubella infection was attempted at 21 to 23 weeks of gestation by measuring rubella-specific IgM by ELISA in blood obtained from 16 fetuses whose mothers had been confirmed rubella infection during pregnancy. Specific IgM was detected in 9 fetuses. In 1 case, the time of the appearance of the rash was 20 weeks of gestation and this pregnancy went to term resulting in a healthy baby without clinical evidence of congenital rubella. The remaining 8 patients had their pregnancies terminated, and fetal infection was confirmed by blood tests after the abortion. No specific IgM was detected in the 7 other fetuses. However, in 2 IgM fetal blood negative cases whose mothers had had the rash at 17 and 20 weeks of gestation, the neonates showed positive IgM findings, but were apparently healthy. The reasons for the false-negative findings are discussed. PMID- 1867579 TI - Puerperal haematomas. AB - Forty-seven out of 31,628 patients delivered in our hospital over the past 5 years developed puerperal genital tract haematomas. Four cases, representing different types of haematoma which required different managements, were presented to illustrate this problem. A literature review was also made. PMID- 1867580 TI - Immediate postoperative oral hydration after caesarean section. AB - A study was carried out to assess the effects of immediate postoperative oral rehydration in 51 unpremedicated women undergoing caesarean section under epidural anesthesia. The patients were randomly assigned to 2 groups: group 1 (n = 22)--fasting at least until 24 hours after the end of the operation, and group 2 (n = 29)--receiving immediate oral intake of fluids (water, tea or coffee with sugar) without limitation of quantity. The 2 groups were compared for the occurrence of postoperative nausea and vomiting, onset of peristalsis, rectal gas emission, first bowel movement, and possible complications. The results demonstrate no significant differences between the parturients who drank immediately postoperatively as compared to those in whom oral fluid intake was delayed for 24 hours or more. It is concluded that immediate postoperative oral rehydration had no harmful effect upon peristalsis post-caesarean section. PMID- 1867581 TI - The comparison of the efficacy among three different nimorazole regimens in the treatment of bacterial vaginosis. AB - The efficacy of 3 different nimorazole regimens in treating bacterial vaginosis in women was evaluated. The regimens consisted of: Nimorazole 2 g single dose (Group I), 1 g per day for 3 days (Group II), and 1 g per day for 7 days (Group III) orally. In a simple randomized trial of 90 cases (30 cases in each group) with demonstrated clinical bacterial vaginosis on the presence of 3 of 5 of the following signs: (1) Characteristic thin homogenous discharge; (2) vaginal pH greater than 4.5; (3) release of a fishy amine odor from vaginal fluid mixed with 10% KOH; (4) presence of clue cells (usually representing at least 20% of vaginal epithelial cells); and (5) vaginal fluid contains few or no lactobacilli. Cure rates for bacterial vaginosis by nimorazole were 70.0% (21/30), 83.3% (25/30), and 90.0% (27/30) in Group I, II, and III, respectively. Thus nimorazole is another effective drug for the treatment of bacterial vaginosis. PMID- 1867582 TI - Low birth weight in Kuala Lumpur. AB - Low birth weight babies are defined as those weighing under 2,500 g. They make 13.5% of all births at the Maternity Hospital, Kuala Lumpur but contribute to 74.8% of all deaths. They are most likely to be Indian babies and least likely to be Chinese. Among all 3 communities, the primigravidae tend to produce smaller babies than multiparae but this is also true for the Indian of parity more than 3. The Malay teenager is more likely to produce small babies than their older counterparts but not so with the Indian and Chinese. There are definite clinical factors associated with or causing the births of small babies and the lighter the baby, the more influential are these factors. Maternal hypertension, antepartum haemorrhage, multiple pregnancy and unexplained intrauterine death are the 4 outstanding associations with both low birth weight and perinatal death. Although the spontaneous (often premature) onset of labour was the commonest preceding factor, it was much less important in the lowest birth weight groups of babies and was a less important contributor to perinatal death. PMID- 1867583 TI - Postmenopausal sexuality in Thai women. AB - We evaluate sexuality in 100 natural menopausal women as pertains to hormones, symptoms related to intercourse, and marital relationship with sexual desire, orgasm and coital frequency. The mean age was 56.8 years while menopausal age was 50.3 years. The postmenopausal syndrome presented 55.0% occurring 1 to 7 years after menopause (mean 3.4 years). The common sexual problems after menopause were loss of libido, orgasmic dysfunction, and dyspareunia. Both sexual desire and activity decreased when compared with premenopausal period. Ninety percent of the subjects had sexual desire less than once a month. Only 14% of the subjects occasionally reached orgasm while the other 86% never had orgasm after menopause. The levels of FSH, LH, estradiol and testosterone were also reported. There was no correlation of hormone estradiol and testosterone, symptoms related to intercourse and marital relationship with sexual desire, orgasm, or coital frequency. PMID- 1867584 TI - Effect of estrogen and progesterone on the growth of human ovarian dysgerminoma heterotransplanted to athymic nude mice. AB - The effects of estrogen and progesterone on the growth of dysgerminoma of ovary heterotransplanted to ovariectomized athymic nude mice (OVX-NUs) were examined. OVX-NUs were divided into 6 groups and a subcutaneous injection of either 1 micrograms or 10 micrograms of estradiol (E1 or E10), 0.1 mg or 1 mg of progesterone (P0.1 or P1), or a combination treatment of E1 and P1 (E1 + P1), or sesame oil as a vehicle control (oil) was given every other day for 2 weeks. Tumor size was recorded every day and the volume doubling time (VDT) was calculated. Tumor bearing OVX-NUs were killed on day 21 and tumor tissue was excised for retransplantation, histological examination and cytosol receptor assay. E10 treatment accelerated tumor growth and shortened VDT to 25 hours compared to 44 hours for the control group. P1 treatment delayed the tumor growth (VDT: 71 hrs) and E1 + P1 treatment further inhibited it (VDT: 197 hrs). E1 or P0.1 did not have any effect on the tumor growth. The levels of both the estrogen receptor (ER) and progesterone receptor (PR) of the original tumor were 5 fmol/mg protein, respectively. Hormone treatment had no remarkable effect, except for a significant increase in PR after estrogen treatment and this result seems to be responsible for the enhanced inhibitory effect of E + P on tumor growth. These effects were also observed histologically. In conclusion, the dysgerminoma used in this study was sex steroid hormone dependent and P alone or in combination with E could be a choice for the treatment of such ovarian dysgerminoma. PMID- 1867586 TI - Time series analysis of biologically active luteinizing hormone concentrations during different stages of the menstrual cycle. AB - The biologically active luteinizing hormone concentrations (as measured by testosterone production by mouse Leydig cells in response to LH) were measured in integrated hourly blood samples collected over 24-hour study periods during different stages of the menstrual cycle from a group of regularly cyclic women. Time series analyses were used to analyse the ultradian rhythms in each individual 24-hour LH profile. Fast Fourier transform (FFT) showed the presence of several ultradian rhythms with different periodicities (varying from 4.4 to 22 hours) in most of the LH profiles. In some of the LH profiles several ultradian rhythms appeared to co-exist. The commonest significant rhythm as detected by the FFT had a periodicity of 7-9 hours during both the follicular phase (40% of the subjects) and the mid cycle (50% of the subjects) and a periodicity of 5-7 hours during the luteal phase (44% of the subjects). PMID- 1867585 TI - Plasma vitamin A and carotene in maternal and cord blood. AB - Mean plasma vitamin A and carotene levels in 200 pregnant women at term were 30.3 mcg% and 43.6 mcg%. Sixty-four percent of women had vitamin A in lower limit of normal (less than 33 mcg%) and 26% had deficient and low levels of carotene. Mean values of plasma vitamin A and carotene in cord blood was 13.7 mcg% and 16.5 mcg%, respectively, and lower than that of maternal blood at term. Women who had adequate levels of vitamin A (greater than 33 mcg%) in blood had significantly higher intake of vitamin A. Similarly the newborn babies of those mothers who had adequate levels of vitamin A had significantly higher levels of vitamin A than those of mothers who had inadequate levels (less than 33 mcg%). PMID- 1867587 TI - Risk determination in cases with an extra minute chromosome: prenatal diagnosis. AB - The interpretation of an extra minute chromosome (EMC) detected in utero presents both diagnostic and prognostic problems. Two EMC cases are presented and a flow chart guideline is proposed for the determination of developmental risk. A prenatally detected EMC was familially inherited through a normal phenotype father. The pregnancy was continued and a normal baby boy was delivered. At one year his development was within normal ranges. The second EMC case was a mentally retarded girl examined at 4 years and 7 months of age. The EMC was identified with a combination of various staining techniques to be an inversion duplication (15). The importance of differential diagnosis of EMCs by DA/DAPI staining is emphasized. PMID- 1867588 TI - Flow cytometric DNA analysis with use of normal lymph node cells as an internal reference standard in ovarian cancer. AB - Fresh frozen and paraffin-embedded tumor specimens of 21 patients with ovarian cancer were investigated by means of flow cytometry. In 4 patients, the fresh frozen tumor specimens (fresh tumor specimens) of ovarian tumors were measured for the DNA ploidy and index. We used the paraffin-embedded normal lymph node tissue specimens which were acquired from retroperitoneal lymphadenectomy as the internal reference standard (IS). In all 21 patients, the paraffin-embedded tumor specimens mixed with a lymph node specimen as an IS (tumor specimen with IS) were measured. In addition, all 21 paraffin-embedded tumor specimens without a lymph node tissue specimen (tumor specimens without IS) were measured. In 4 cases which were measured with the fresh tumor specimens, all 4 tumor specimens with IS had the same patterns of DNA ploidy as the fresh tumor specimens. Of 21 patients, 6 patients showed different DNA ploidy patterns between the tumor specimens with and without IS. Furthermore, all of these 6 patients showed diploidy in the tumor specimens without IS while showing aneuploidy in the tumor specimens with IS. Fourteen (66.7%) of 21 tumor specimens with IS were aneuploidy despite aneuploidy of only 8 (38.1%) tumor specimens without IS. All 4 patients with stage I had diploidy in the tumor specimens with IS, and 13 (81.3%) of 16 patients with stage III or IV had aneuploidy. All 8 patients with diploidy in the tumor specimens with IS had survived for 1-2 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867589 TI - Measles immunisation in Australian children. PMID- 1867590 TI - Life threatening infections. AB - The importance of the rare infections discussed in this article lies in their potential for causing illness and death and the need for prompt and often specific management. Some are associated with characteristic features; others, however, are non specific in presentation. Only a high index of suspicion will ensure correct diagnosis and treatment. PMID- 1867592 TI - Notification of disease. Worthwhile or not? AB - Disease notification is part of the community surveillance system for control of infectious diseases, but it has fallen into disuse. Understanding the goals and mechanisms of surveillance allows us to respond most appropriately to the needs of both our patients and the community. PMID- 1867591 TI - Update on HIV infection. AB - With more effective therapies and prophylaxis for HIV infection and its sequelae, survival is steadily improving. This article outlines some of these recent advances in therapy as well as the epidemiology, transmission and natural history of the infection. Prolonged survival and the trend towards earlier intervention have resulted in an increasing role for the primary physician. Clinical and laboratory monitoring of the 'asymptomatic' patient are discussed, with emphasis on selection of the most appropriate times for various medical interventions. PMID- 1867593 TI - Common skin infections. AB - A variety of skin infections is seen in general practice. Because the diagnosis can often be made clinically, therapy can be initiated before laboratory results are obtained. Some of the common skin infections are discussed in this article. PMID- 1867594 TI - Conjunctivitis. AB - Most cases of conjunctivitis are either viral in origin, which makes them extremely contagious and usually self-limited, or bacterial, which usually requires topical antibiotic therapy. Prolonged follicular conjunctivitis should be considered chlamydial in origin and requires systematic antibiotic therapy. PMID- 1867595 TI - Cholesteatomatous otitis media. AB - Cholesteatomas are cysts or sacs of keratinising squamous epithelium found in the middle ear cleft. The presentation of these lesions may be similar to that of chronic otitis media, but because of their predisposition towards major complications, surgery is the treatment of choice. PMID- 1867596 TI - Journal clubs for general practitioners. AB - Journal clubs are one of the principal means by which hospital-based specialists keep up-to-date and engage in clinical discussion. General practitioners often feel isolated in their surgeries, and have limited opportunities to participate in discussion of journal articles, peer review or case presentation. A journal club run by general practitioners in their homes is described and recommended to all family physicians as an excellent learning experience. PMID- 1867597 TI - Bicipital tendinitis. PMID- 1867598 TI - Mastalgia. AB - Mastalgia (breast pain) is the commonest breast problem women present with in general practice. Mastalgia can be apparent, when due to referred pain or costochondritis, for instance; or real, when it can be localised or diffused. Diffused pain can be cyclical or non cyclical. An important association of cyclical mastalgia is benign mammary dysplasia (fibroadenosis). It is important to exclude malignancy and to reassure patients. PMID- 1867599 TI - Nerve blocks for the face. PMID- 1867600 TI - Patient education. Mastitis. PMID- 1867601 TI - Withdrawal wobblies. PMID- 1867602 TI - Functional status measures in general practice. WONCA Classification Committee. AB - The International Classification Committee of WONCA met in Sydney in July 1990 to further develop functional status measures for use in general practice and to plan revision of the International Classification of Primary Care (ICPC) and other classifications for primary care (Further reading). This paper is the first in a series on functional status measures and classification arising from the meeting. It presents an overview of the discussions and outcomes. PMID- 1867604 TI - The false negative mammogram. PMID- 1867603 TI - Some 'sort of vascular phenomenon'. PMID- 1867605 TI - Another headache. PMID- 1867606 TI - Australian Rational Recovery--a new approach to chemical dependency. PMID- 1867607 TI - Incidence of Q fever. PMID- 1867608 TI - Towards effective surgical audit. PMID- 1867609 TI - Developing a system for surgical audit. AB - A system for surgical audit, which has been developed during a 6 year period in an active surgical unit of a teaching hospital, is described. Following a review of the first 3 years of our computerized audit, major modifications to the audit processes and computer program were made. The key lessons for systematic practical surgical audit include the collection of essential data only, establishing audit processes within current department practices, verification of data by consultants, and the provision of incentives for all users. The current system is proving a valuable resource for quality assurance, surgical training and departmental management. PMID- 1867611 TI - General surgical manpower, Victoria, Australia. AB - To provide information for the planning of general surgical manpower in Victoria for the next 2 decades, an attempt was made to establish a statewide profile of surgical practices and an analysis of surgical activity to determine whether surgeons' and the community's needs were being met. Of 343 practising general surgeons, 280 furnished returns to a questionnaire--a return rate of 81.6%. Responses to the questionnaire reveal that the current surgeon-to-population ratio is optimal, although certain imbalances and concerns exist. Surgeons are fully occupied regardless of age, location of practice or type of practice, and they work long hours. Most surgeons regard themselves as not overworked and most are satisfied, although not all do the type of work they would prefer. Current surgical training programmes, however, appear inadequate for future needs. PMID- 1867610 TI - Experience with biliary audit. AB - Experience with an audit of surgery for gallstones is discussed. Three hundred and forty-six patients were treated in a three and a half year period. There was no mortality. There was a duct exploration rate of 17%, an infection rate of 8.6%, and a re-operation rate for retained bile duct stone of 1.6%. Bile was cultured from 278 gall-bladders and culture was positive in 66 cases (23.7%). The most common organisms grown were coliforms and streptococci. Our antibiotic policy has changed as a result of this study. Audit is becoming increasingly necessary in surgical practice, not only for research purposes, but also to monitor performance. The design can be broad, to identify groups of patients for further study, or narrow, to concentrate on a particular problem. Someone must be responsible for checking the completed forms for accuracy before the data are entered into the computer. It is important that the form be as simple as possible. Forms which are too detailed will be filled in inaccurately or not at all. PMID- 1867612 TI - Regionalization of trauma services in western Sydney: predicted effect on ambulance and hospital utilization rates. AB - A previous study has demonstrated the effectiveness of ambulance staff in identifying the majority of trauma victims who warrant admission to a Level 3 Hospital. This paper applied the results of that study in order to estimate the likely effect of a system of bypass whereby these identified patients are transported to a Level 3 hospital rather than the nearest Level 1 or 2 Hospital. Under the proposed plan whereby both Westmead and Liverpool Hospitals would be granted Level 3 status, the effect of Westmead would be negligible. However, Liverpool's caseload would increase (25% for total admissions, 136% for serious admissions) and, consequently, its level of resources would need to be upgraded before this plan can be put into action. Meanwhile, Level 1 and 2 hospitals would see little change to total patient admissions, although there would be a substantial drop in serious admissions (-63%). Under the proposed system, the effects on the Ambulance Service would also be negligible in terms of both the number of transports and total transport hours. However, the nature of these transports would change. More time would be required in bypass cases, although this would be compensated for by a corresponding fall off in interhospital transfers (28% decline in time spent on transfers). Ultimately, this means that patients would be getting to the hospital of definitive care much sooner. These results have implications for the development of trauma services in other sectors. PMID- 1867613 TI - Basal skull fractures. A prospective study of 100 consecutive admissions. AB - A prospective study of 100 consecutive patients with basal skull fracture admitted to the University Hospital, Kuala Lumpur between July 1986 and October 1988 was carried out to study its epidemiological pattern, clinical and radiological presentations, mechanisms of injury, time interval between accidents and neurosurgical referrals, complications and outcomes. Two-thirds of the patients were between 20 and 50 years old and 79% were male. Half of the injured were motorcyclists and 22% were pedestrians. Three-quarters of the patients were seen within an hour after injury. Thirty-two patients had intracranial haematomas: 14 subdural, 9 extradural and 9 intracerebral. Three patients developed meningitis (two after operations) and six developed epilepsy. Eighteen patients died, but good recovery resulted in 70 patients at follow-up of 1 to 28 months. A small subgroup of 15 patients with severe ear and nose bleeding as a result of basal venous sinus tear died within a few hours despite aggressive resuscitation, probably due to underlying severe brain stem injury. The implication of the high incidence of basal skull fractures in motorcyclists, despite the enforcement of crash helmets is discussed, with possible mechanisms proposed. PMID- 1867614 TI - Intussusception in Newcastle in a 25 year period. AB - The history of intussusception in Newcastle in a quarter of a century is presented by analysis of patient presentation and the results of management. The figures for the early years are incomplete, retrieved from one hospital in the area. For the years 1976-1988, all cases were managed by two paediatric surgeons who kept individual disease indices. One hundred and sixty-five episodes of intussusception in 153 patients were reviewed in this study. There was one death in the series, whereas there had been several in the years preceding it. There has been an improvement in the success of hydrostatic and later pneumatic reduction. These changes are attributed to the development of appropriate skills resulting from concentration of the management of this problem in the hands of paediatric surgeons and radiologists with special training and interest in paediatrics. Enema reduction has been used more aggressively in recent years and has widened criteria. In the series there were 8 patients with causal lead points, none associated with recurrence. The overall recurrence rate within the series was estimated at 8%. There seems to be a high incidence of intussusception in doctors' families. PMID- 1867615 TI - Comparison of the performance of visual and verbal multiple-choice questions. AB - A study was carried out to determine whether multiple-choice questions based on visual trigger material, such as micrographs, photographs or radiographs, were more difficult and more discriminating than corresponding verbal questions testing: (i) the same information; (ii) different information in the same content area. Seventy-seven question triplets, each of which contained a visual (X) question, a verbal (Y) question testing the same information and a verbal (Z) question testing different information in the same content area were set in twelve Part 1 FRACS examinations. The questions were arranged in such a way that the X and Z questions in a triplet were set in the same examination, while the Y question was set in the corresponding examination of the previous or the following year. The specific outcomes studied were those on facility index and r biserial discriminating index. An analysis of variance on the data pertaining to each index did not indicate significant differences among the groups. None of the differences between pairs of mean facility indices among question groups X, Y and Z was found to be significant at P less than 0.05, nor were any of the differences between pairs of r biserial discriminating indices found to be significant at P less than 0.05. It was concluded that visual questions set in the Part 1 FRACS examination were not demonstrably more difficult or more discriminating than the corresponding verbal questions. The findings do not detract, however, from the obvious importance of visual recognition for future surgeons. PMID- 1867617 TI - Wound infiltration with 0.25% bupivacaine not effective for postoperative analgesia after cholecystectomy. AB - The instillation of local anaesthetic agents into surgical wounds has been reported to be an effective method of reducing pain and narcotic requirements, using both local injection and topical application techniques. We performed a double-blind trial to test the value of the long-acting local anaesthetic, bupivacaine, in this role. Eighty patients undergoing elective cholecystectomy were entered into the study. They were divided into 2 groups of 40 patients to compare a local injection technique with a topical application technique. For each route of application, 20 patients received a test solution containing 0.25% plain bupivacaine, and 20 received 0.9% NaCl as a control. Postoperative analgesia in the form of intramuscular pethidine (1-1.5 mg/kg) was made available to all patients on request. The degree of postoperative pain was assessed using three criteria: the time from operation to the first request for analgesia, the total dose of postoperative pethidine required during the first 3 postoperative days and the patient's rating of pain on a 10 cm linear analogue scale at 24 h and 72 h. There was no statistically significant difference between the degree of postoperative pain experienced by patients receiving bupivacaine and those receiving NaCl, when assessed by any criterion. There was also no significant difference found between patients receiving bupivacaine by local infiltration and those receiving the drug topically. It is concluded that the local application of bupivacaine to the wound is not an effective analgesic technique following laparotomy for cholecystectomy. PMID- 1867618 TI - Brachiobasilic fistula with autogenous basilic vein: surgical technique and pilot study. AB - This pilot study examined the efficacy of the brachiobasilic fistula formed by a loop of autogenous basilic vein in 15 consecutive patients requiring secondary access. The technique of its construction is also described. The fistula survival at 1 year was 70% and at 2 years was 50%. The major complications were late fistula thrombosis and stenosis. No patient developed an infected fistula or chronic forearm oedema. Fistula assessment monitoring was used to verify the patency of the fistula. This study provides preliminary evidence that this fistula is useful as a secondary access. A randomized prospective study of saphenous vein, basilic vein and polytetrafluoroethylene for secondary access construction would establish the relative merits of these three conduits. PMID- 1867616 TI - Effects of Furegrelate (Upjohn 63557A) on patency and platelet deposition after canine carotid endarterectomy. AB - Platelet deposition upon endarterectomy sites is a likely cause for early postoperative thrombosis, embolism and restenosis. Platelets aggregate by the thromboxane-prostacycline mechanism. Thromboxane synthetase inhibitors which have been safely administered to humans should reduce platelet deposition after surgical therapy and therefore reduce peri-operative mortality and the prevalence of stroke. A randomized prospective controlled trial was designed to determine vessel patency and platelet deposition associated with the use of 3 mg/kg and 30 mg/kg of Furegrelate (Upjohn U63557A) daily in dogs, who were to have carotid endarterectomy. The 46 treated and 46 control dogs had total carotid patency of 96% and 76% respectively (P less than 0.01). Fourteen dogs treated with 30 mg/kg Furegrelate had no occlusions, compared with a 19% prevalence in 13 controls (P less than 0.02). Furegrelate 10 mg/kg significantly lowered platelet aggregation. Platelet deposition was not significantly changed, however. The reason for this disparity was a probable persistence of vessel wall factors which promoted platelet deposition. This approach might therefore lower rates of peri-operative thrombosis but it would be very unlikely to alter the incidence of restenosis or embolism. Further research could be directed towards modifying the stimuli for platelet deposition upon the endarterectomy site. PMID- 1867619 TI - Mid-ileal stricture and spinal injury sustained by a 7 year old child restrained by a lap seat belt involved in a motor vehicle accident. AB - Lap belts are a feature of the middle seat occupant in the rear seat of most Australian family cars. Without the provision of a child harness, they are inadequate to restrain children under eight years of age. We report a motor vehicle accident involving a seven year old child wearing an adult lap belt which resulted in an ileal stricture and a potentially unstable distraction injury of the lumbar spine. PMID- 1867620 TI - An example of unusual distal venous spread in rectal cancer. AB - A patient with a distal venous metastasis of a carcinoma of the rectum is reported. This is an unusual finding and a suggested mechanism for its occurrence is discussed. PMID- 1867621 TI - Primary carcinoid tumour of the ileum associated with massive gastrointestinal haemorrhage. AB - A case of massive gastrointestinal haemorrhage due to a 3 mm primary carcinoid tumour of the ileum is described. Previously described instances of this problem have been due to larger tumours. The site of the haemorrhage was suggested by a technetium-labelled RBC isotope scan. The lesion was visualized by 'on-table' endoscopy via the colon and ileo-caecal valve. The patient did well after segmental resection of the lesion. This case highlights the diagnosis and current approach to massive lower gastrointestinal haemorrhage. PMID- 1867622 TI - Cortical neuroanatomical correlates of behavioral deficits produced by lesion of the basal forebrain in rats. AB - Morphological changes in the frontoparietal cortex were assessed in rats that exhibited deficits in a go/no go alternation task due to electrolytic lesion of the basal forebrain. Cortical area, laminar thickness, neuronal density, and soma area were examined in frontal, hindlimb, forelimb, and parietal areas of the cortex. Quantitative morphological analysis of the frontoparietal cortex in lesioned rats revealed a decrease in laminar thickness due to reduced soma size in particular cortical laminae. Neuronal density was not affected. These effects were present in all cortical areas examined and most pronounced in laminae II III. Similar morphological changes were observed in the same cortical areas following lesions of the basal forebrain made with ibotenic acid, allowing a discrimination of lesion effects from those induced by damage to fibers of passage or differential behavioral testing. Lesions of the basal forebrain have previously been shown to produce both behavioral deficits and changes in cortical cholinergic activity. The cortical morphological changes observed in the present study following basal forebrain lesion provide further evidence for the importance of ascending cholinergic inputs to the cortex and their role in learning and memory. PMID- 1867623 TI - Mere exposure to telereceptive cues facilitates intake of a novel flavor in chickens (Gallus domesticus). AB - This experiment investigated whether mere exposure to visual cues of a distinctively colored solution (water) would facilitate intake of a novel flavor (vinegar) of the same distinctive color. Eighty-four chicks received access to clear water, clear vinegar, red water, or red vinegar under conditions which permitted drinking or they received access to clear water or red water under conditions (mere exposure) which prevented drinking. All chicks were then tested on intake of red vinegar. Chicks which had received mere exposure or ingestional experience with red-colored water drank reliably more red vinegar than did chicks which had received prior ingestional experience with the novel taste, vinegar, but not with the visual cues of red. However, intake of red vinegar was reliably greater following ingestional experience with red water than following visual exposure without ingestion. Results supported the mere exposure hypothesis. PMID- 1867624 TI - Learning and memory of a water T-maze by rats selectively bred for low or high plasma catecholamine stress responses. PMID- 1867625 TI - Effects of post-training ethanol and group housing upon memory of an appetitive task in mice. AB - It has been shown that post-training ethanol's facilitating effects upon memory disappeared if the mice were kept isolated after training. Since ethanol-treated mice were attacked by their cagemates, it has been hypothesized that the improved retention induced by ethanol resulted from an interaction between ethanol and group housing which added aversive information to training. To investigate the correctness of this interpretation, ethanol effects upon memory of an appetitive task were studied. C57BL/6J mice (isolated the day before training) were individually trained to find a cheese pellet placed in a corner of an open-field. Mice were injected intraperitoneally immediately after training with saline, 0.5, 1.5, or 2.0 g/kg of ethanol. They were then returned to their home cage and left alone, with another mouse, or with five other mice for 2 h after training. All mice were tested 24 h later for retention. Reductions in the number of pellet approaches or in the latency to eat the pellet were taken as measures of learning. Post-training ethanol disrupted retention of the appetitive task in a dose-related manner. Moreover disruption was greater in mice group housed after training. The results support the hypothesis that ethanol's post-training facilitating effects upon aversive memory may be due to added aversive information to the stimulus complex, rather than, or in addition, to enhanced storage of memory traces. PMID- 1867626 TI - Time-dependent sequential increases in [14C]2-deoxyglucose uptake in subcortical and cortical structures during memory consolidation of an operant training in mice. AB - Previous results have suggested that memory processing may involve the sequential activation of subcortical and cortical structures. To study this phenomenon, we have examined the immediate (15 min) and delayed (220 min) metabolic changes produced in BALB/c mice by a partial training session in a bar-pressing appetitive task, using the [14C]-2-deoxyglucose (2-DG) relative glucose uptake method. These relative metabolic changes were compared to the ones produced in several control groups: untrained animals, sham-conditioned animals, overtrained animals, and animals forced to walk on a moving belt (immediate and delayed condition). Animals were given a single intrajugular injection (5 microCi) of 2 DG either 5 min before or 3 h (delayed condition) after the second training session. Forty minutes after the 2-DG injection, the animals were sacrificed and their brains processed for autoradiography. At the 15-min delay, a large 2-DG labeling increase was found in partially trained animals for various subcortical areas (septum, diagonal band, hippocampus, thalamus, and mammillary bodies) while a much smaller increase was found in four cortical areas (frontal, cingulate, parietal, and sensory motor cortices). At the 220-min delay, we observed a large 2-DG labeling increase in cortical (frontal, pyriform, and cingulate cortices) and subicular areas while a moderate 2-DG labeling increase was observed in entorhinal cortex and the diagonal band. These results show that, shortly after training, subcortical structures are preferentially activated while cortical structures are much less activated. Three hours later, at a time when retention performances have been shown to improve spontaneously in the same strain of mice and in the same task, cortical structures are highly activated. PMID- 1867627 TI - Time-dependent effects of post-trial amphetamine treatment in rats: evidence for enhanced storage of representational memory. AB - Two studies were conducted to test the ability of post-trial amphetamine treatment to improve later recall in a nonaversively motivated task. These studies utilized 8- and 12-arm radial mazes, respectively, with an 11-h retention interval imposed after the rat traversed half the arms of the maze (termed, the to-be-remembered-event, or TBRE). In Experiment 1, the rats were injected with amphetamine (0, .25, and .50 mg/kg) immediately after the TBRE. Because the drug treatment improved retention, a time dependency study was conducted in which the drug (0 and .33 mg/kg) was administered 0, 3, and 6 h after the TBRE. The finding that amphetamine injection at 0, but not 3, h post-trial improved later recall indicates that the benefit derived from the former treatment is not due to proactive influences at the time of the retention test. Drug treatment 6 h post trial produced a borderline improvement of recall; possible mechanisms are discussed. Two conclusions can be drawn from these results: (1) amphetamine administration can improve recall under conditions in which this effect cannot be attributed to alterations in information processing during either the learning or the retention sessions, indicating that the drug modulates memory storage processes; and (2) amphetamine treatment can improve working memory, thus excluding an alternative interpretation for the previous reports of impaired short-term memory in animals, all of which entailed assessments of working memory. The possibility remains, however, that the impairment seen in these tasks reflects the requirement for erasure of information from previous trials within each daily session, rather than the duration of the retention interval. PMID- 1867629 TI - Simplifying environmental cues in a Morris-type water maze improves place learning in old NMRI mice. AB - Old virgin female NMRI mice aged 17 months were compared with mice aged 3 months for their spatial learning abilities in two versions of the Morris water maze. The first one was a simplified version with a salient configuration of cues comparable to a black/white discrimination and the second one was the classical version of the Morris test with many distal cues surrounding the maze. In the simplified version, old mice presented a slower rate of acquisition and a transient poorer retention compared to young mice. However, old mice achieved a final level of performance statistically comparable to their young counterparts as assessed by latencies to escape onto the concealed platform and by the spatial bias measured in probe trials at intervals during testing. When subsequently subjected to classical Morris maze learning, the same old animals showed marked learning deficits and were persistently impaired in their latencies to escape onto the platform. They presented no spatial bias for the location of the platform in the different probe trials. When the goal was cued at the end of the experiment, the performances of old mice rapidly improved, showing that motivation, motor disabilities, or fatigue and ability to use proximal cues cannot explain the place learning deficit. Our results were discussed in terms of cognitive versus sensory/perceptual disabilities in aged rats and mice. PMID- 1867628 TI - Amnesia induced by 2-deoxygalactose in the day-old chick: lateralization of effects in two different one-trial learning tasks. AB - 2-Deoxy-D-galactose, an inhibitor of brain glycoprotein fucosylation, was injected intracranially (10 mumole dose in 10 microliters) into either the left or the right forebrain hemisphere of day-old chicks (Gallus domesticus). Bilateral injection of this dose of 2-deoxy-D-galactose is known to induce amnesia for several learning tasks including one-trial passive avoidance and sickness-induced learning. When a tritiated form of the drug was injected into one forebrain hemisphere only, a significantly large proportion of the dose remained in that hemisphere. Chicks were trained in two different one-trial learning tasks. The first was a passive avoidance task in which the chicks were allowed to peck at a green training stimulus (a small light-emitting diode, LED) coated in the bitter liquid, methylanthranilate, giving rise to a strong disgust response and consequent avoidance of the green stimulus. In the second paradigm the chicks were allowed to peck at a similarly colored dry stimulus but, 30 min later, were injected intraperitoneally with lithium chloride (0.1 ml of 1 M solution), causing a sickness-induced aversion for the green LED. 2-Deoxy-D galactose caused amnesia for the passive avoidance task when injected before training into the right hemisphere but not the left. However, unilateral injection of the drug before training on the sickness-induced learning task did not cause amnesia. The results indicate that fucosylation of brain glycoproteins is required in the right hemisphere for learning the passive avoidance task but that memory for sickness-induced learning can be retained by either hemisphere. PMID- 1867630 TI - Role of angiotensin II in the processes leading to ovulation. PMID- 1867631 TI - Antitumor activity and biochemical effects of topsentin. AB - Topsentin, a bis(indolyl)imidazole marine natural product, inhibited the proliferation of cultured human and murine tumor cells at micromolar concentrations (IC50 values ranged from 4 to 40 microM) and was active against in vivo P388 leukemia (%T/C = 137, 150 mg/kg, QD1-5) and B16 melanoma (%T/C = 144, 37.5 mg/kg, QD1-9) tumors. Effects of 30 microM topsentin (1-hr exposures) on incorporation of radiolabeled precursors by P388 cells indicated inhibition of DNA synthesis (91%) and to a lesser extent RNA synthesis (57%), whereas synthesis of protein was unaffected (0%). Fluorescence spectral changes and competitive binding experiments with ethidium bromide indicated that topsentin interacted with DNA. No evidence for intercalation was observed in DNA unwinding studies, but competitive binding experiments with Hoechst 33342 and CC-1065 indicated that topsentin bound to DNA in the minor groove. PMID- 1867633 TI - Human ribonucleotide reductase. Activation and inhibition by analogs of ATP. AB - Sixteen ATP analogs were studied as activators of CDP reduction catalyzed by human ribonucleotide reductase. Activation constants were determined. Three analogs, 3-deazaATP, 5'-adenylimidodiphosphate, and 3'-dATP, activated approximately as efficiently as ATP. Four analogs were partial activators. These seven activators were also accessory activators of GDP reduction. Furthermore, two other analogs, adenosine-5'-O-(1-thiotriphosphate) and 8-bromoATP, selectively stimulated GDP reduction. Ten analogs, at equal molar concentrations with ATP, inhibited ATP-dependent activation of CDP reduction and/or accessory activation of GDP reduction by greater than 45%. No analog inhibited as potently as 2'-dATP, which had an IC50 of 30-50 microM versus the stimulation of CDP and GDP reduction by 2.0 mM ATP. PMID- 1867632 TI - The expression of human cytochrome P450IA1 in the yeast Saccharomyces cerevisiae. AB - Data from animal studies suggest that cytochrome P450IA1 catalyses the metabolic activation of several procarcinogenic compounds. In the present study, we have expressed human cytochrome P450IA1 in yeast cells. A 1.70 kb BclI/BamHI fragment containing a full-length human cytochrome P450IA1 cDNA was inserted into the BglII expression site of the yeast expression plasmid pMA91 thereby allowing the ATG initiation codon to be located adjacent to the PGK (phosphoglycerate kinase) promoter. The resulting recombinant plasmid, pCK-1, was introduced into Saccharomyces cerevisiae strains ATCC 44773 and AH22. Microsomes prepared from yeast transformatants of strain ATCC 44773 contained undetectable levels of cytochrome P450. In contrast, microsomes from strain AH22 contained cytochrome P450 with a specific content of 33.3 +/- 10.8 pmol/mg of microsomal protein and showed a reduced carbon monoxide difference spectrum with a peak at 448 nm. Control yeast cells transformed with pMA91 showed no cytochrome P450. Western blots were carried out using an antibody that reacts against rat cytochrome P450IA1 and an antibody that reacts against a synthetic peptide representing a short sequence of human cytochrome P450IA1. A band with a molecular weight of 54 kD was observed in microsomes of yeast transformed with pCK-1, but not with pMA91. When microsomes from yeast transformed with pCK-1 were incubated with benzo(a)pyrene (10 min, 10-160 microM), an estimated Km value of 7 microM was obtained. The availability of yeast cells with functionally active human cytochrome P450IA1 will facilitate molecular structure-activity studies of procarcinogen and drug metabolism by this enzyme in man. PMID- 1867634 TI - Induction of a 31,000-dalton stress protein by prostaglandins D2 and J2 in porcine aortic endothelial cells. AB - Prostaglandin (PG) D2 and PGJ2 stimulated porcine aortic endothelial cells to synthesize a 31,000-dalton protein (termed p31) in a time- and concentration dependent manner. The induction of p31 synthesis was specific for PGD2, PGJ2 and PGA1 among the various PGs tested. p31 was also synthesized in response to the thiol-reactive agent diethylmaleate and heavy metal sodium arsenite but not to high temperature treatment, platelet-derived growth factor, and 12-O tetradecanoylphorbol 13-acetate. Using two-dimensional polyacrylamide gel electrophoresis, p31 induced by PGJ2 had an isoelectric point of 5.4, which overlapped exactly with that induced by by arsenite. These results taken together indicate that p31 represents one of the stress proteins whose expression is regulated primarily by thio-active compounds but not by hyperthermia. Furthermore, it was induced by PGD2 and PGJ2 in rat capillary endothelial cells, rat skin fibroblasts, and rat hepatocytes. The data obtained from this study suggest that p31 induced by PGD2 and PGJ2 may play a role in the metabolic regulation of many mammalian cells. PMID- 1867636 TI - Mitochondrial effects of the guanidino group-containing cytostatic drugs, m iodobenzylguanidine and methylglyoxal bis (guanylhydrazone). AB - The involvement of mitochondrial damage in the antiproliferative effects of m iodobenzylguanidine [MIBG] and methylglyoxal bis (guanylhydrazone) [methylGAG] was studied in human neuroblastoma SK-N-SH, mouse neuroblastoma N1E115 and mouse lymphosarcoma S49 cells. Proliferation of SK-N-SH cells was insensitive to MIBG (100 microM gave 15% inhibition), but sensitive to methylGAG (IC50 = 50 microM). MIBG and methylGAG were approximately equitoxic to N1E115 cells (IC50 of 92 and 87 microM, respectively). S49 cells were most sensitive to both MIBG (IC50 = 11 microM) and methylGAG (IC50 = 5 microM). In isolated sonicated mitochondria, MIBG inhibited respiration a complex I of the respiratory chain (EC50 = 0.5 mM), whereas methylGAG was much less effective (EC50 greater than 15 mM). In intact cells, MIBG at 31 microM impaired mitochondrial respiration and stimulated the glycolytic flux. In contrast, equimolar concentrations of methylGAG had no effect on oxygen consumption, ATP content, glucose consumption and lactate production. MethylGAG significantly increased putrescine levels in N1E115 and S49 cells within 12 hr via inhibition of S-adenosylmethionine decarboxylase. No such effects were seen in SK-N-SH cells for up to 48 hr. Equimolar concentrations of MIBG had no effect on the putrescine levels in the various cell lines, suggesting that MIBG did not inhibit S-adenosylmethionine decarboxylase. It is concluded that the antiproliferative mechanisms of the guanidino compounds are essentially different. MIBG inhibited mitochondrial respiration at complex I with concomitant stimulation of the glycolytic flux but was essentially without effect on polyamine levels. On the other hand, cytotoxicity of methylGAG was not associated with mitochondrial dysfunction. PMID- 1867635 TI - Comparative effects of LN 5330 and diazoxide on insulin release and 86Rb+ permeability in perifused rat islets of Langerhans. AB - The benzothiadiazine derivative LN 5330 (chloro-7 trifluoromethyl-6 benzothiadiazine-1,2,4-dioxide-1,1) has been shown to inhibit insulin secretion and calcium uptake. The present study was carried out to investigate the effects of LN 5330 on insulin release and 86Rb- efflux from perifused rat pancreatic islets; a comparison was made with the structural analogue diazoxide. In the presence of 8.3 mM glucose, LN 5330 (100 microM) accelerated 86Rb+ efflux while reducing insulin output from the islets. LN 5330 induced a dose-dependent acceleration of 86Rb+ efflux and appeared to be a more potent activator of 86Rb+ efflux than diazoxide. The stimulatory effect of LN 5330 on 86Rb+ efflux persisted in the absence of extracellular calcium. In the absence of glucose, 86Rb+ permeability also increased, LN 5330 being again significantly more efficient than diazoxide at an equimolar concentration. These data indicate that the benzothiadiazine derivative LN 5330 inhibits insulin secretion by increasing the potassium permeability of the plasma membrane. It is suggested that, like diazoxide, this drug could activate the ATP-sensitive K+ channel. PMID- 1867637 TI - Protein binding of indomethacin in human cerebrospinal fluid. AB - The binding of the non-steroidal anti-inflammatory drug indomethacin to proteins in human cerebrospinal fluid (CSF), drawn during lumbar puncture from 10 patients affected by lumbosciatica, was measured by equilibrium dialysis and spectrofluorimetry. Similar binding studies on human serum albumin solutions (0.5 and 1 g/L) were performed using the same techniques. The mean binding percentage of indomethacin determined by equilibrium dialysis was 40%. The results obtained by both techniques allowed us to conclude that the binding of indomethacin in CSF was essentially due to albumin. PMID- 1867638 TI - Effects of toluene on platelet membrane glycoprotein Ib and actin-binding protein. AB - Effects of the organic solvent toluene on the platelet membrane receptor glycoprotein Ib (GP Ib) and the cytoskeletal protein, actin-binding protein (ABP), were studied and related to the effects of the local anesthetic dibucaine. The glycocalicin-region of GP Ib contains the binding site for von Willebrand factor; intracellularly GP Ib is linked to the cytoskeleton via ABP. Both GP Ib and ABP are substrates for a calcium-dependent protease, calpain. Washed platelets were incubated with toluene or dibucaine. The toluene concentration in the platelet suspension was analysed by gas chromatography. Using 1.5-2.8 mmol/L toluene, calpain was activated, leading to degradation of ABP and release of glycocalicin from GP Ib. The latter phenomenon was paralleled by a reduced von Willebrand factor-induced platelet agglutination. At lower toluene concentrations (0.3-1.4 mmol/L), degradation of ABP was not detected but an initial increased agglutination that declined to the control level with time was observed. These effects of toluene on the GP Ib-ABP complex are similar to those observed with 1 mmol/L dibucaine. The lowest toluene concentrations used correspond to those that have been found in blood from toluene abusers ("sniffers"). PMID- 1867639 TI - In vitro metabolism of 5,8-dideazafolates and 5,8-dideazaisofolates by mammalian folylpoly-gamma-glutamate synthetase. AB - The in vitro metabolism of a variety of 5,8-dideazafolate and 5,8 dideazaisofolate analogues by pig liver folylpolyglutamate synthetase and the specificity of the enzyme for some polyglutamate derivatives of these analogues have been investigated. All 4-oxo-quinazoline analogues were metabolized to long chain polyglutamate derivatives, primarily the pentaglutamate, whereas 4-amino quinazolines were metabolized to a lesser extent, with the accumulation of di- and triglutamate derivatives. This pattern of metabolism was consistent with the large drop in Vmax/Km and Vmax values for folylpolyglutamate synthetase observed with diglutamate derivatives of 4-aminofolate analogues. The extent of metabolism of the various analogues did not correlate with the relative substrate effectiveness of their parent monoglutamate derivatives. The 5-chloro and 5 methyl substitutions of quinazolines enhanced the addition of glutamate residues to 4-amino derivatives but markedly impaired the metabolism of 4-oxo derivatives. PMID- 1867640 TI - The effects of bucillamine on glutathione and glutathione-related enzymes in the mouse. AB - The effect of bucillamine (BA) on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of high doses of BA (150-400 mg/kg) produced a dose-dependent depletion (20-44%) of hepatic GSH, which was similar in magnitude to that produced by equimolar doses of other sulphydryl drugs studied previously. GSH depletion after acute BA administration correlated well with the elevation of serum glutamic-pyruvic transaminase (SGPT) (6-9-fold increase above control). The increase in SGPT after chronic administration (7 days), although significantly higher than the controls, was however much less than after acute administration. The hepatic GSH concentrations of mice given 7 days of BA were similar to the controls, again correlating well with SGPT activity. Administration of BA (150-400 mg/kg) caused also a significant dose-dependent increase in the oxidized glutathione (GSSG) in blood by 2-7-fold, as well as a dose-dependent increase in blood glutathione S-transferase (GST) activity (2-13 fold). In an in vitro experiment, hepatic GST activity was activated by various concentrations of BA (1 microM-1mM). There was little or no effect on GSSG reductase and on glutathione peroxidase (GSH-Px) after acute administration of BA. Chronic administration of BA had no effect on hepatic GSSG reductase and GSH Px, but GSSG reductase activity in blood was increased significantly by 4-fold. It is possible that BA may affect the redox status through auto-oxidation and oxidation with endogenous thiols such as glutathione, affecting GSH concentrations and the GSH/GSSG ratio in tissues and, thus, having both metabolic and toxicological consequences. Whether or not the induction of GST activity in vivo in blood and in vitro in liver enzyme preparations shared the same underlying mechanism(s) requires further investigation. PMID- 1867641 TI - In vitro effects of bryostatin 1 on the metabolism and cytotoxicity of 1-beta-D arabinofuranosylcytosine in human leukemia cells. AB - Bryostatin 1 is a macrocyclic lactone protein kinase C (PK-C) activator which has demonstrated promising antileukemic activity in preclinical studies. We have examined the effect of this agent on the metabolism and cytotoxicity of 1-beta-D arabinofuranosylcytosine (ara-C) in both log phase and high-density human promyelocytic leukemia cells (HL-60). Exposure of low-density cells to 12.5 nM bryostatin 1 for 24 hr prior to a 4-hr incubation with 1 or 10 microM ara-C resulted in nearly a 2-fold increase in ara-CTP formation. When cells were maintained under high-cell density conditions (e.g. 5 x 10(6) cells/mL) for 24 hr prior to ara-C exposure, a 90% reduction in ara-CTP formation and ara-C DNA incorporation was observed. However, coincubation of high-density cells with bryostatin 1 for 24 hr increased ara-CTP formation 6- to 8-fold, yielding levels essentially equivalent to those achieved in low-density cells. Smaller (but still significant) increases in ara-C DNA incorporation were also noted. Enhancement of ara-CTP formation by bryostatin 1 occurred over a broad ara-C concentration range (0.1 to 100 microM), involved a temperature-dependent process, could not be mimicked by addition of hematopoietic growth factors, and was not related to neutralization of toxic or inhibitory substances in high-density medium. Exposure of cells to bryostatin 1 did not lead to morphologic or functional evidence of HL 60 cell maturation or an increase in cell viability, but did produce a decline in cellular proliferative activity as determined by thymidine and bromodeoxyuridine incorporation and cytofluorometric analysis. Bryostatin 1 did not exert its effects in high-density cells by inhibiting ara-C deamination or by interfering with ara-CTP dephosphorylation, but instead appeared to act by enhancing ara-C phosphorylation. Although cell-free extracts obtained from high-density cells exposed to bryostatin 1 exhibited levels of deoxycytidine kinase activity compared to controls, treated cells did display a significant decline in intracellular dCTP levels (e.g. 0.7 vs 1.3 pmol/10(6)), and nearly a 2-fold increase in ATP and UTP concentrations. Ara-CTP formation was also increased substantially by other PK-C activators including phorbol dibutyrate and mezerein (10-100 nM); this process was inhibited more than 70% by the PK-C inhibitor H-7 (50 microM), but not by the PK-C inhibitors staurosporine, tamoxifen, and HA1004. Finally, coadministration of ara-C and bryostatin 1 resulted in greater than expected inhibitory effects toward HL-60 cell clonogenic growth.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1867642 TI - Effects of toluene and its metabolites on cerebral reactive oxygen species generation. AB - The effects of toluene on lipid peroxidation and rates of reactive oxygen species (ROS) formation have been studied in isolated systems and in vivo. The induction of reactive oxygen species was assayed using the probe 2',7'-dichlorofluorescin diacetate (DCFH-DA). Toluene exposure (1 g/kg, 1 hr, i.p.) did not stimulate cortical lipid peroxidation as evaluated by measurement of conjugated dienes. Exposure to toluene, however, both in vivo and in vitro, caused a significant elevation of ROS formation within cortical crude synaptosomal fractions (P2) and microsomal fractions (P3). The ROS-inducing properties of toluene were blocked in vivo in the presence of a mixed-function oxidase inhibitor, metyrapone. This suggested that a metabolite of toluene may catalyze reactive oxygen formation. Both benzyl alcohol and benzoic acid, in vitro, were found to have free radical quenching properties, while benzaldehyde exhibited significant induction of ROS generation. It appears that benzaldehyde is the metabolite responsible for the effect of toluene in accelerating reactive oxygen production within the nervous system. Benzaldehyde may also contribute to the overall neurotoxicity of toluene. PMID- 1867643 TI - Relationships between ascorbic acid and alpha-tocopherol during diquat-induced redox cycling in isolated rat hepatocytes. AB - The effects of diquat-induced redox cycling on the levels of cellular ascorbic acid and alpha-tocopherol were investigated in isolated rat hepatocytes. In untreated hepatocytes, the metabolism of 1 or 2 mM diquat resulted in the depletion of cellular ascorbic acid and glutathione, but not of alpha-tocopherol, in association with the induction of cell death during the experimental period. In 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) pretreated cells, 1 mM diquat induced cell death accompanied by glutathione was rapid (to 9% of controls by 15 min) and cell ascorbate was completely consumed by 2 hr of incubation. In contrast, cellular alpha-tocopherol levels were stable for the first 30 min, but were depleted in association with the onset of lipid peroxidation. Supplementation of 0.1 or 1.0 mM ascorbic acid in the incubation medium delayed the onset of diquat-induced alpha-tocopherol loss, lipid peroxidation and cytotoxicity. When the concentration of exogenous cellular ascorbic acid was consumed to below that of endogenous ascorbic acid, alpha-tocopherol loss and lipid peroxidation were initiated. The results indicate that untreated hepatocytes have an effective multicomponent antioxidant system against diquat induced oxidative stress. However, when glutathione is depleted from hepatocytes by treatment with BCNU and diquat, ascorbic acid plays a vital role in maintaining cellular alpha-tocopherol levels and survival of the cell. PMID- 1867644 TI - Mechanism of deiodination of 125I-human growth hormone in vivo. Relevance to the study of protein disposition. AB - Examination of the disposition of proteins employing 125I-labeled tracers can be complicated by the in vivo deiodination of the tracer. The purpose of this study was to characterize the mechanism by which 125I-labeled proteins are deiodinated in vivo using 125I-human growth hormone (hGH) as a model compound. Intravenous (i.v.) administration of 125I-hGH resulted in a biphasic plasma kinetic pattern, with the majority of radioactivity removed from the plasma during the first 15 min. The level of circulating radioactivity at 2 hr was similar to that 15 min after administration. Radioactivity was eliminated from the animals almost exclusively in the urine. The chemical form of radioactivity in the plasma and urine was analyzed by HPLC, and precipitation of radioactivity with silver nitrate or trichloroacetic acid. Fifteen minutes after administration of 125I hGH, 30% of the circulating radioactivity was present in the form of iodide (125I ). By 2 hr, the majority of radioactivity in the plasma was in the form of 125I-. The radioactivity in the urine was present exclusively in the form of 125I-. In vivo deiodination of 125I-hGH was reflected by the accumulation of radioactivity in the thyroid glands. There was no evidence for the presence of 125I-peptide intermediates in the plasma or urine of treated animals. In vitro, 125I-hGH was degraded to 125I-peptide intermediates by thyroid gland but not liver or kidney homogenates. In the absence of cofactors, 125I- was not observed as an in vitro metabolic product. However, in the presence of dithiothreitol and NADPH as cofactors, the predominant metabolic product formed by thyroid gland homogenates was 125I-. The deiodination of 125I-hGH by thyroid gland homogenates was inhibited by the serine protease inhibitor phenylmethylsulfonyl fluoride (PMSF), indicating that proteolysis of 125I-hGH was required for deiodination to occur. This was supported by the observation that 125I-labeled proteolytic fragments of 125I-hGH, but not 125I-hGH, were deiodinated by liver or kidney homogenates in the presence of these cofactors. Deiodination by thyroid gland homogenates was inhibited by the sulfhydryl-group blocking reagent, iodoacetate, in a concentration-dependent manner. The characteristics of the in vitro deiodination reaction suggest that a form of thyronine 5'-monodeiodinase may be involved in the in vivo deiodination of 125I-hGH and possibly other 125I-proteins. These data suggest that the disposition of proteins may be determined more accurately with 3H-, 14C- or 35S-labeled molecules which better represent the characteristics of the native protein. PMID- 1867645 TI - Thymidine and zidovudine metabolism in chronically zidovudine-exposed cells in vitro. AB - Chronic exposure of H9 cells to 25 microM zidovudine (H9-AZT cells) causes a 2- to 3-fold increase in thymidine kinase (TK) activity (Agarwal RP, Int J Purines Pyrimidine Res, in press). The present study compared thymidine (TdR) and AZT anabolism in H9 and H9-AZT cells. After a 3.5-hr incubation with 10 microM TdR or AZT, the total intracellular accumulations of AZT (48.7 microM in H9 cells and 32.8 microM in H9-AZT cells) were 46.4% of TdR accumulation. Other major differences between TdR and AZT anabolism were: (i) the majority of TdR (84-87%) was incorporated into DNA compared to less than 1% of AZT; and (ii) whereas distribution of TdR in the nucleotides was TTP greater than TMP greater than TDP, zidovudine distributed was AZT-MP much greater than AZT-TP much greater than AZT DP. Because of the poor substrate activity of AZT-MP for thymidylate kinase (TMP kinase), most of the AZT (95-98%) remained as AZT-MP. TMP-kinase activities with TMP as substrate were 47.6 +/- 20.3 and 91.4 +/- 28.8 pmol/mg protein/min in H9 and H9-AZT cells, respectively. 5'-Nucleotidase activities with TMP as substrate were 428.9 +/- 37.8 and 255.9 +/- 28.7 pmol/mg protein/min in H9 and H9-AZT cells, respectively. Activities of these enzymes with AZT-MP as a substrate were very low. Despite an increase in TK and TMP-kinase, and a decrease in 5' nucleotidase activities, the total intracellular accumulations of TdR and AZT were reduced significantly (P less than 0.05) to 67.5% in H9-AZT cells. Thymidine transport (0.66 to 0.68 pmol/sec/10(6) cells) was similar in both the cell lines. The severe reductions of TdR salvage caused by chronic exposure of cells to AZT, if it occurs in AIDS patients on AZT chemotherapy, may explain some of the long term clinical toxicities of the drug. PMID- 1867646 TI - The effects of lofepramine and desmethylimipramine on tryptophan metabolism and disposition in the rat. AB - Acute and chronic administration of lofepramine and its major metabolite desmethylimipramine (DMI) to rats elevates brain tryptophan concentration, thereby enhancing cerebral 5-hydroxytryptamine (5-HT) synthesis, by increasing the availability of circulating tryptophan to the brain, secondarily to inhibition of liver tryptophan pyrrolase (tryptophan 2,3-dioxygenase, L tryptophan:O2 oxidoreductase, decyclizing; EC 1.13.11.11) activity. The pyrrolase inhibition by lofepramine occurs independently of metabolism to DMI, because it can be demonstrated directly in vitro. Lofepramine also differs from DMI in its action profile on the above and related aspects of tryptophan metabolism and disposition. These results demonstrate that lofepramine influences tryptophan and 5-HT metabolism and disposition independently of its major metabolite DMI, and are discussed briefly in relation to the mechanism of action of antidepressants. PMID- 1867648 TI - Assessment of the mouse as an experimental model for studying polymorphic oxidation of the sparteine/debrisoquine type. PMID- 1867647 TI - Effect of paracetamol on mitochondrial membrane function in rat liver slices. AB - The effect of paracetamol on mitochondrial function was studied using rat liver slices. Changes in the potential of the mitochondrial and plasma membrane were monitored using [3H]-triphenylmethylphosphonium (TPMP+) and [14C]thiocyanate (SCN ) probes, respectively. Liver slices were exposed to 10 mM paracetamol for various time periods (0-360 min) after loading with TPMP+. The release of TPMP+ which correlates with a decrease in the mitochondrial membrane potential became significant after 30 min incubation with 10 mM paracetamol. The change in the mitochondrial membrane potential was shown to be independent of cytochrome P450 activity. No significant change in plasma membrane potential was observed, until the release of lactate dehydrogenase (LDH) had begun, 4 hr after exposure, reflecting the ultimate stages of cell injury by paracetamol. These results suggest that paracetamol elicits a direct effect on the mitochondrial function before cell injury develops and adds further evidence to the role of mitochondria in paracetamol toxicity. PMID- 1867650 TI - Idebenone, an agent improving cerebral metabolism, stimulates [14C]tyrosine uptake and [14C]catecholamine formation by cultured bovine adrenal chromaffin cells. PMID- 1867649 TI - Metabolism of T-2 toxin by rat brain homogenate. AB - HT-2 toxin was the sole metabolite formed when T-2 toxin was treated with homogenate from brain without its blood content. Homogenate from brain with its full blood content produced--besides HT-2 toxin--T-2 triol, neosolaniol, 4 deacetylneosolaniol and T-2 tetraol, i.e. the same metabolites formed by incubation of T-2 toxin with whole rat blood. PMID- 1867652 TI - Comparison of the chromatographic characteristics of metabolites of tacrine hydrochloride in human serum and urine with those of in vitro metabolic products from hepatic microsomes. AB - There may be as many as five metabolites of THA in man, four corresponding to products in the rat. The study provides some evidence that one of major metabolites is 1-hydroxy-THA but lends no support to the putative oxidative deamination pathway. PMID- 1867651 TI - Effects of chloroquine and primaquine on rat liver cytosolic N-acetyltransferase activity. AB - Chloroquine caused only slight reductions in NAT activity when added in vitro, and had no detectable influence when animals were pretreated with it for 4 days. This would suggest that the previously reported reduced excretion of acetylated metabolites of INH and SDD following chloroquine pretreatment is not the result of inhibition of NAT. In contrast, we found that primaquine significantly (P less than 0.05) reduced NAT activity when added in vitro, suggesting the need for further study with this agent. PMID- 1867654 TI - Pharmacological evaluation of certain novel prolonged-acting local anaesthetics. In vivo rat sciatic nerve block. AB - Some new 2-phenoxyethyldialkylamines in previous studies had proved to be superior to other standard drugs in respect of local anaesthetic activity. To confirm their intensity and duration of action, the two outstanding compounds were selected for further pharmacological studies on the rat sciatic nerve preparation in vivo. Their activity and duration of action were determined by a double-blind controlled trial (at the later stage) and in two stages. The test compounds showed comparable rates of onset of motor analgesia (5-10 min). They also displayed quick recovery from complete analgesia, typically being around 10 min after the first sign of a recovery of motor function was observed. In addition, no systemic or local untoward effects were noticed. Bupivacaine produced drowsiness in the rats. PMID- 1867653 TI - General pharmacology of a new potent 5-hydroxytryptamine antagonist. AB - The potential of the investigational 5-hydroxytryptamine (5HT3) antagonist, LY277359, to alter cardiovascular, central nervous system (CNS), smooth muscle, and gastrointestinal functions at multiples of pharmacologically active doses, was examined to provide a profile of possible secondary pharmacological effects. In the anesthetized dog, significant cardiovascular effects were observed at doses 100-1000 and 4-15 times those found to be pharmacologically active at 5HT3 receptors in vivo in rats and dogs, respectively. These effects were limited to decreased heart rate (approximately 20%) at intravenous doses of 1.75 and 3.5 mg/kg and prolonged Q-Tc intervals (approximately 20 to 50%) at doses of 0.438 to 3.5 mg/kg. At an oral dose of 135 mg/kg (representing 1500-4500 times the pharmacologically active dose in rats), LY277359 induced hypoactive behavior and reduced body temperature in mice. Seizure activity was potentiated at high oral doses of LY277359 (45 and 135 mg/kg). A single oral dose of 135 mg/kg increased hexobarbital-induced sleep time. In smooth and cardiac muscle tissue studies in vitro, LY277359 was essentially inactive: it did not alter contractile activity or receptor function of the guinea pig ileum, rat vas deferens, rat uterus, or guinea pig atria at concentrations of 10(-5) to 10(-10) mol/l. At a concentration 50,000 times the 5HT3 antagonistic level in vitro (10(-4) mol/l), LY277359 inhibited the response of the ileum to field stimulation, acetylcholine and angiotensin I, and suppressed the rate of the spontaneously beating guinea pig atria in a noncompetitive manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867655 TI - Inhibitory effects of nisoldipine on serotonin and potassium induced contractions of porcine coronary and femoral arteries. AB - The inhibitory effect of nisoldipine (Baymycard, Syscor; CAS 63675-72-9) and nifedipine on the serotonin and potassium induced contractions of porcine coronary and femoral arteries in vitro has been investigated. Both nisoldipine and nifedipine inhibited preferentially the serotonin induced contraction in the coronary artery being less effective in the inhibition of the femoral artery. The coronary selectivity of nisoldipine is at least 10 times more pronounced than that of nifedipine. The serotonin antagonist ketanserin inhibited contractions on both vessels with the same potency. The potassium induced contraction was inhibited by the dihydropyridines in both coronary and femoral artery. Nisoldipine again, was more potent than nifedipine in the inhibition of coronary artery spasm but not in the contraction of femoral artery. Ketanserin did not inhibit contractions of any vessels. PMID- 1867656 TI - In vitro/in vivo evaluation of hydrochlorothiazide in experimental hydrochlorothiazide/triamterene combination tablets in beagle dogs. AB - The purpose of this study was to compare experimental formulations containing hydrochlorothiazide (CAS 58-93-5)/triamterene (HCT/TRI) in vitro and in vivo to a commercial tablet formulation (standard). The beagle dog was verified as a good model and was used for the in vivo studies. The commercial tablet and the experimental fast release formulation (FR) resulted in 100% release of HCT within 30 min in dissolution tests, whereas, the slow release formulation (SR) released only 54% HCT after 4 h. Relative bioavailability of the FR and SR formulations were 82 and 41%, respectively, compared to the commercial tablet. The experimental results indicate that HCT absorption occurs throughout the small intestine. PMID- 1867657 TI - [Bioavailability and bioequivalence of organic nitrates. Isosorbide dinitrate--a study of sustained-release preparations]. AB - Assessment of Bioavailability of Organic Nitrates/Comparative bioavailability study of sustained-release isosorbide dinitrate preparations. Relative bioavailabilities of isosorbide dinitrate (ISDN, CAS 87-33-2) and the metabolite isosorbide-5-mononitrate (IS-5-MN, CAS 16051-77-7) were studied after application of Maycor retard 40 (sustained-release capsules, multiple unit formulation, test preparation) in comparison to sustained-release tablets (single unit formulation, reference preparation) with 16 healthy male volunteers in a two-way crossover design. Test and reference formulations were previously characterised in vitro by dissolution tests. ISDN, IS-5-MN (IS-2-MN) plasma concentrations were determined using a selective and sensitive GLC-method with ECD-detection. As pharmacokinetic parameters AUC, Cmax and half value duration (HVD) were evaluated. Bioequivalence was assessed by calculating 90%-confidence intervals (ANOVA, ANOVAlog, Mann Whitney-test) for ISDN and IS-5-MN. Bioequivalence was accepted if due to the inclusion rule one of the calculated intervals fulfill the requirements of 80 and 120% (AUC) or 70 and 130% (Cmax, HVD), respectively. Relative bioavailability of the test formulation was calculated as 94% (ISDN) and 96% (IS-5-MN). Maximum plasma concentrations of ISDN (IS-5-MN) were determined for the test preparation as 14.3 +/- 3.1 ng/ml (265 +/- 45 45 ng/ml) and as 22.8 +/- 12.6 ng/ml (287 +/- 59 ng/ml) for the reference product. HVD-values were for the test preparation 4.5 +/- 1.3 h (ISDN) and 8.5 +/- 1.3 h (IS-5-MN) and for the reference formulation 3.1 +/- 1.2 h (ISDN) and 8.1 +/- 1.4 (IS-5-MN).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867658 TI - Activity of a novel thienodiazepine derivative as a platelet-activating factor antagonist in guinea pig lungs. Effects on platelet-activating factor and allergen induced eosinophil accumulation. AB - Platelet-activating factor (PAF) inhalation in guinea pigs caused a significant increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). Oral administration of (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl 8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123), a novel PAF antagonist, at the dose of 100 micrograms/kg completely inhibited the PAF-induced eosinophil accumulation. Antigen inhalation in passively sensitized guinea pigs caused a significant increase in lung contents of PAF at 5 min, and accumulation of eosinophils in the bronchi 1 and 2 days thereafter, E-6123 inhibited the antigen induced eosinophil accumulation and the maximum inhibition was approximately 65%. On the other hand, methylprednisolone completely inhibited the antigen-induced eosinophil accumulation. The results suggest that PAF is a potent attractant of eosinophils and is involved in antigen-induced eosinophil infiltration into bronchi. The results also suggest that E-6123 may be of therapeutic value in the treatment of asthma exhibiting eosinophil recruitment in airways. PMID- 1867660 TI - Bioequivalence of two formulations of piroxicam. AB - Two separate studies were performed with 12 volunteers in order to demonstrate the bioequivalence of 2 piroxicam (CAS 36322-90-4) tablet and 2 piroxicam suppository formulations after single dose administration. A validated reversed phase HPLC method with UV-detection is described. Bioequivalence assessment was done by using the posterior probability of a mean ratio between 0.8 and 1.2, and by using the Two One-Sided Tests Procedure (i.e. the 90% confidence interval). The probability approach and the confidence interval approach were compared. PMID- 1867659 TI - Studies on the anti-phospholipase A2 and anti-inflammatory activities of a synthetic nonapeptide from uteroglobin. AB - The nonapeptide H-Met-Gln-Met-Lys-Lys-Val-Leu-Asp-Ser-OH (antiflammin), corresponding to a high amino acid similarity region of uteroglobin was prepared by solution and solid phase synthesis. The peptide do not inhibit pancreatic phospholipase A2 in vitro and the carrageenin-induced oedema in vivo. PMID- 1867661 TI - Possible mechanism of the gastroprotective activity elicited by some copper(II) complexes. AB - The gastroprotective activity of some copper(II) complexes has been previously described. Since mucus secretion may be a factor responsible for their gastroprotective activity, this study was designed to determine the influence of these compounds on mucous secretion in rat. The copper complexes assayed at a dose of 25 mg/kg significantly increased mucous secretion. Pre-treatment with indometacin, a cyclooxygenase inhibitor, does not influence the mucostimulant properties of these compounds. However, the effect on mucus secretion was significantly decreased by pre-treatment with a depletor of endogenous thiols, n ethylmaleimide. These results suggest the additional role of sulfhydryl groups in the mucosal gastroprotective effect of copper(II) complexes. PMID- 1867662 TI - [Comparison of the bioequivalence of two allopurinol preparations]. AB - Allopurinol generally is considered to be a problematic substance as to its bioavailability. To prove the quality, the in-vivo bioequivalence of an allopurinol (CAS 315-30-0) preparation (Cellidrin 300) in comparison to the standard preparation has been investigated. Both products were bioequivalent with regard to all relevant parameters such as AUC, tmax and Cmax. PMID- 1867663 TI - In vitro and in vivo effects of N-methyl-3,5-dichloro-benzylamine hydrochloride on Mycobacterium leprae. AB - The antimicrobial effects of a new benzylamine, ME-93 (N-methyl-3,5-dichloro benzylamine hydrochloride), alone and in combination with dapsone and rifampicin, have been evaluated in vitro in cell-free culture system and in vivo in mouse foot pad system. Even at 50 micrograms/ml, ME-93 did not completely inhibit the in vitro growth of M. leprae, and the effects were bacteriostatic. However, there was a synergism when ME-93 was combined with rifampicin, and the effects were bactericidal. Similar findings were also obtained in the mouse foot pad system. Thus, there is a new drug that needs further attention in the chemotherapy of leprosy. PMID- 1867664 TI - Pharmacokinetics of cefotiam in plasma, parotid saliva and mixed saliva in healthy adults. AB - Cefotiam (Spizef; CAS 61622-34-2) at a dose of 2 g was administered intravenously to 10 young, healthy, male volunteers. Multiple simultaneous blood, parotid saliva, and mixed saliva samples were collected for 7 h. The antibiotic assay was carried out by high-pressure liquid chromatography. Significant salivary cefotiam concentrations were found for 2 to 4 h, potentially inhibitory to a wide array of pathogens commonly isolated from the upper aerodigestive tract. Salivary cefotiam concentrations were correlated to plasma levels (p less than 0.01), but saliva/plasma ratios varied considerably. It is unlikely that passive diffusion is the applicable transfer mechanism for cefotiam secretion into saliva. PMID- 1867665 TI - Synthesis and biological screening of aminothiadiazine dioxides related to trimethoprim. AB - New derivatives of 3-amino-1,2,6-thiadiazine 1,1-dioxide have been synthesized and their antibacterial, antifungal and DHFR inhibitory activities evaluated. Their chemical structures have been established by means of analytical and NMR spectroscopic data. Among the compounds studied, the 4,4-dibromo derivative 11 showed fungistatic activity against C. albicans. PMID- 1867666 TI - Biological activity of bacterial surface components. Immunogenicity and immunomodulatory properties of a bacterial extract from Escherichia coli. AB - The immunogenic and immunomodulatory properties of a lysed fraction from selected E. coli strains (OM-89, Uro-Vaxom) were determined in vivo and in vitro. It could be demonstrated that OM-89 constitutes an active immunogen in mice. Maximum OM-89 specific antibody titers were obtained after 4-5 i.p. immunizations; the titers could be further enhanced by the simultaneous injection of lipopeptide adjuvants. It was shown by ELISA that the antibodies obtained bound to the bacterial strains used for the preparation of the OM-89 extract. Immunogenicity was observed both after intraperitoneal and oral application of the extract. Besides being active as an immunogen. OM-89 was able to act in vitro as a polyclonal lymphocyte activator, as determined in splenocyte cultures of different inbred murine strains, and in cultures of human peripheral blood lymphocytes. Our results show that the B lymphocyte stimulating activity of the bacterial extract OM-89 was comparable to that of lipopeptide adjuvants. In conclusion, the bacterial extract both an active immunogen in vivo, and a polyclonal B cell activator in vitro. These findings may be of importance for the understanding of the therapeutic effect of OM-89. PMID- 1867667 TI - An outbreak of designer drug--related deaths in Pennsylvania. AB - 3-Methylfentanyl ("China White") is a "designer" opiate that has caused more than 100 overdose deaths in California since 1979, but that has not been associated previously with deaths east of the Rocky Mountains. During 1988, 3-methylfentanyl was identified in 16 fatal overdose cases in Allegheny County, Pennsylvania, contributing to a fourfold rise in overdose mortality during October of that year. Morphine was detected in the blood of five persons (31%) and cocaine in the blood of three persons (19%) dying of 3-methylfentanyl overdoses; these were demographically similar to 99 other fatal overdose cases investigated by the county coroner from 1986 through 1988. This documents the contribution of 3 methylfentanyl to overdose mortality in an eastern city and the use of 3 methylfentanyl with other illegal drugs. Drug abusers in the northeastern United States should be considered at risk for more "designer drug" overdose outbreaks in the future. PMID- 1867668 TI - AIDS in Thailand. PMID- 1867669 TI - NIH Technology Assessment Conference statement on bovine somatotropin. PMID- 1867670 TI - EMF--cancer link still murky. PMID- 1867671 TI - A New Zealand code of ethics. PMID- 1867672 TI - The probability of obtaining compatible blood from related directed donors. PMID- 1867674 TI - We cannot afford an AIDS epidemic. PMID- 1867673 TI - Global warming and health. PMID- 1867675 TI - Heparin-induced thrombocytopenia. PMID- 1867676 TI - Aneurysms of the sinus of Valsalva in Chinese patients. PMID- 1867677 TI - A requiem for vagotomy. PMID- 1867678 TI - Jarman index. PMID- 1867679 TI - Naevoid hypertrichosis. PMID- 1867680 TI - Aneurysm formation in experimental atherosclerosis: relationship to plaque evolution. PMID- 1867681 TI - Clearing up "infection". PMID- 1867682 TI - Serodiagnosis of Lyme disease. PMID- 1867683 TI - The relationship between maternal hematocrit and pregnancy outcome. PMID- 1867684 TI - At the water's edge: where obstetrics and anesthesia meet. PMID- 1867685 TI - Draping the claustrophobic patient. PMID- 1867686 TI - Oxygen cylinders on anaesthesia machines. PMID- 1867687 TI - Changing disease patterns in AIDS. PMID- 1867688 TI - Health check ups in middle age. PMID- 1867689 TI - Postviral fatigue syndrome. PMID- 1867690 TI - Irreducible inguinal hernia. PMID- 1867691 TI - Imprecision of the stratus immunoassay system for free thyroxin. PMID- 1867692 TI - Seven-point checklist for melanoma. PMID- 1867693 TI - Antibiotic treatment for pregnant victims of Lyme disease. PMID- 1867694 TI - Competency based training. PMID- 1867695 TI - Ethics in preventive medicine. PMID- 1867696 TI - The NFL's drug testing policy. PMID- 1867697 TI - Glucose-6-phosphate dehydrogenase deficiency. PMID- 1867698 TI - Comments on commentary by D. Billen. PMID- 1867699 TI - Closure of veterinary investigation centres. PMID- 1867700 TI - Progression of coronary stenosis. PMID- 1867701 TI - Hypoprothrombinemia and cephalosporins. PMID- 1867702 TI - PTCA-induced coronary-left ventricular fistula. PMID- 1867703 TI - Comments on life after residency. PMID- 1867704 TI - Anesthesia and funic acid-base values. PMID- 1867705 TI - Panty hose-pants disease. PMID- 1867707 TI - T-cell-rich B-cell lymphomas. PMID- 1867706 TI - Borderline personality diagnosis in children and adolescents. PMID- 1867708 TI - 'Finger-painting' and the pulse oximeter. PMID- 1867709 TI - Aspirin concurrently administered with ranitidine does not delay healing of duodenal ulcer. PMID- 1867710 TI - The white pulmonary resuscitator. PMID- 1867711 TI - Optical method. AB - I have traced the development of the optical method from Millikan's colorimetry of cat muscle myoglobin to today's high-frequency laser diode time-resolved phase modulation system study of hemoglobin and myoglobin in muscle and brain in adult humans. The path length as well as specific absorption information is obtained in terms of the rate of photon decay or by equivalent measurements using phase modulation. Localization of inhomogeneities of deoxyhemoglobin concentrations in stroke and head injury appears possible. PMID- 1867712 TI - Bacterial chemotaxis and the molecular logic of intracellular signal transduction networks. PMID- 1867713 TI - The zipper-like folding of collagen triple helices and the effects of mutations that disrupt the zipper. PMID- 1867714 TI - Calcium spiking. PMID- 1867715 TI - Statistical methods and insights for protein and DNA sequences. PMID- 1867716 TI - Beyond gene sequencing: analysis of protein structure with mass spectrometry. PMID- 1867717 TI - Structure and function of a lipoprotein: lipovitellin. PMID- 1867718 TI - High-resolution structures of photosynthetic reaction centers. PMID- 1867719 TI - Ultrasonic velocimetry of biological compounds. PMID- 1867720 TI - Time-resolved photoacoustic calorimetry: a study of myoglobin and rhodopsin. PMID- 1867721 TI - Chloramphenicol acetyltransferase. PMID- 1867722 TI - Direct observation and manipulation of single DNA molecules using fluorescence microscopy. PMID- 1867723 TI - Polymer principles in protein structure and stability. PMID- 1867724 TI - From femtoseconds to biology: mechanism of bacteriorhodopsin's light-driven proton pump. PMID- 1867725 TI - Defining solution conformations of small linear peptides. PMID- 1867726 TI - Water-protein interactions: theory and experiment. PMID- 1867727 TI - Biological applications of scanning probe microscopes. PMID- 1867728 TI - [Etiological factors in oral cancer]. PMID- 1867729 TI - [Effectiveness and tolerance of Diclofenac vs. Nefopam in treatment of postoperative pain]. PMID- 1867730 TI - [Effectiveness of chemical products as antiplaque agents]. AB - We review the antiplaque effectiveness of distinct chemical products. We considered two types, depends on the "in vitro" or "in vivo" demonstrable effect. PMID- 1867731 TI - [Irreversible pulp pathology in young permanent teeth. A treatment approach]. AB - Is made a remember for the two biological elements which audit on the root physiological formation: the dental pulp and the Hertwig's epithelial root sheath. Is discussed like on the practice clinic, we can find undamaged both elements, or we have only with the Hertwig's epithelial root sheath. We indicate a treatment when we have a vioble dental pulp, like different treatment if only we have the Hertwig's epithelial sheath. Is remembered rules which help to keep the health of the periodontal tissues, preventing to the same initiation and preventing too the immunologic reactions. PMID- 1867732 TI - [Nifedipine induced gingival hyperplasia]. AB - Nowadays we have a whole of drugs, Calcium antagonists (AC), like Verapamil (VE), Nifedipine (NI), Diltiazem (DI), used in cardiovascular therapy. One of them, Nifedipine, has several side effects, out of which is gingival overgrowth. In the present article we present four cases, in which have been analyzed this effect and its resolution in one of them, after drug suppression and patient's hygienic habits correction. PMID- 1867733 TI - [Behavior patterns in the dental office]. PMID- 1867734 TI - [Relationship between malocclusion and TMJ dysfunction. Literature review]. AB - The purpose of this paper is to discuss some current concepts of maloclusion and TMJ Syndrome by reviewing the most significative literature. This analysis the great differences between well-knowing authors about very important subjects in occlusion, as the condylar position in centric relation and in TMJ Syndrome, or what kind of malocclusion (morphologic and functional, skeletal or dental) was the cause of TMJ Syndrome. The theory of emotional stress would be useful to explain some of the discrepancies, by reducing the occlusal disharmony to predisposal factors depending on the personal adaptation to stress. PMID- 1867735 TI - Improvement of phase III psychotropic drug trials by intensive phase II work. AB - Phase III drug trials are expensive, time-consuming procedures that too often are a disappointment, since the evidence for drug efficacy proves marginal and unconvincing. We believe that this can be remedied by attention to numerous correctable flaws during Phase II. These multiple problems require a structural solution. The development of expert, psychopharmacologic facilities that focus on deficient areas of Phase II studies so as to develop an adequate Phase III design should prove helpful. PMID- 1867737 TI - Prescribing privileges for non-physicians in the military. Accepted as a Consensus Statement by the ACNP Council, March 22, 1991. PMID- 1867736 TI - Baseline corrections in experimental and quasi-experimental clinical trials. AB - Three methods of correcting for baseline differences are evaluated for use with randomized experimental designs and nonrandomized quasi-experimental designs. Cases where baseline means differ significantly in spite of random assignment and cases where observed baseline means do not differ significantly in quasi experimental designs are given special attention. For comparison of treatment induced change in randomly constituted treatment groups, analysis of covariance (ANCOVA) provides appropriate type I error protection and superior power regardless of the apparent significance of chance baseline differences. Correcting for baseline differences by expressing outcome scores as percentage of the baseline value for each individual produces results that closely approximate ANCOVA under specified conditions. Tests on simple pre-post difference scores are nonconservative when baseline means differ significantly in spite of randomization. In quasi-experimental research where treatment groups represent samples from different predefined populations, ANCOVA and percentage change provide inadequate baseline corrections even when the observed baseline means do not differ significantly. Although no method of baseline correction is entirely satisfactory in the absence of random assignment, tests on simple pre-post difference scores are generally superior for quasi-experimental designs in which treatment groups represent samples from different populations. PMID- 1867738 TI - A simple method for determining breast and chest wall thickness. AB - When planning radiotherapy for primary breast cancer, it is essential to determine the thickness of the chest wall in mastectomized patients and of the intact breast in patients undergoing conservation therapy. A simple method, based on the use of the simulator, to determine breast and chest wall thickness is described. PMID- 1867739 TI - Surface topography for patient repositioning. AB - For many years, this group has been interested in the measurement of patient surface contours in order to prepare radiotherapy compensators. Recently, these surface measurements have been made using optical ranging techniques (Medical Physics 16:425; 1989). A laser line is projected onto the patient surface and the video image of the line is digitized and used to calculate the coordinates of each point on the line. This surface information can be used not only for the calculation of compensators but can also be used to verify patient position from simulation to treatment and from one treatment to another. Because the calculation of surface coordinates takes approximately 30 seconds, the technique has been modified to allow the comparison of setup position in real time. In the new system, a series of narrow fan beams is projected to intersect the patient surface. At simulation, the reference video image of the lines is digitized and stored. At treatment setup, repeat video images are digitized and compared with the reference in real time. Operator adjustments to patient position are immediately shown on the composite image, and a congruency value is calculated to help in this process of alignment. Uses and accuracy of the technique will be discussed. PMID- 1867740 TI - Border separation for adjacent orthogonal fields. AB - Field border separations for adjacent orthogonal fields can be calculated geometrically, given the validity of some important assumptions such as beam alignment and field uniformity. Thermoluminescent dosimetry (TLD) measurements were used to investigate dose uniformity across field junctions as a function of field separation and, in particular, to review the CCSG recommendation for the treatment of medulloblastoma with separate head and spine fields. PMID- 1867741 TI - [Does a cholera risk exist in Mexico?]. PMID- 1867742 TI - [The quantitative analysis of thyroid hormones and thyrotropin in children critically ill with septicemia]. AB - The function of the hypothalamus, hypophysis, and thyroid glands was studied in 23 critically-ill septicemic children and 15 other healthy children used as controls. A comparison in the quantification of 3,3'5-triiodothyronine (T3), 3,3',5'triiodothyronine (T3r), thyroxine (T4) and thyrotropin (TSH) from those in the control group with the initial values from the patients showed a notable decrease of T3 and T4 and a rise in T3r and TSH in the septicemic children, with a statistical significant difference (P less than 0.001). These biochemical changes which translate into a homeostatic command to avoid catabolism through the conservation of energy, spontaneously returned to normal in 18 of the surviving septicemic children once they recuperated. PMID- 1867743 TI - [The use of beverages and food at home during acute infantile diarrhea: an ethnographic study in a rural Mexican area]. AB - A structured interview was applied through a personal interview to 142 peasant mothers aimed at exploring some beliefs about childhood diarrheal disease and the use of home-made beverages and feeding habits during the illness. The majority answered they used to give a herbal tea (90%) or a rice-based beverage (77%) to their child with diarrhea. Only 18% mentioned the use of oral rehydration packages. Sixty-three percent avoid certain foods while 25% withhold all food, usually for more than 24 hours, to a sick child. It is justified to assess the clinical efficacy of a rice-powder solution in the prevention of severe dehydration, as well as to promote an uninterrupted diet based on locally accepted and available foods, in the home management of a child with acute diarrhea. PMID- 1867744 TI - [Congenital hip dislocation and the seasons]. AB - This report deals with the data gathered for a year concerning the incidence of luxation coxae congenita at the Hospital de Gineco-Obstetricia (Gynecology Obstetrics Hospital) of the Unidad Medica Oblatos (Oblatos Medical Unit) of the Instituto Mexicano del Seguro Social (Mexican Institute of Social Security) in the city of Guadalajara, Jalisco, Mexico. The results show an inverse correlation between the temperature and the number of cases, both statistically significant, demonstrating seasonality for luxation coxae congenita. PMID- 1867745 TI - [A comparative study of technics for intestinal anastomosis]. AB - Two different intestinal anastomosis techniques were compared in 10 mongrel dogs. The first was classical enteral anastomosis (CEA) and the second was "U" suture enteral anastomosis (UEA) performed with "U" separated suture and inverted intestinal edges in one layer. The follow-up was over 21 days average. Once the follow-up was finished, animals were reoperated to obtain gut with CEA and UEA for macroscopic measures and microscopic studies with hematoxilin-eosin stains. UEA was easier and faster than CEA and lesser fibrotic and inflammatory tissue reaction were showed as well as lesser stenosis in UEA group. Both techniques had similar seal in anastomosis suture line as mean similar security. We think that UEA gives enough trust and security to be performed for good training surgeons. PMID- 1867746 TI - [The Fanconi-Bickel syndrome]. AB - This is a case of a 15-month-old child suffering from Fanconi-Bickel syndrome, characterized with Fanconi syndrome manifestations (glycosuria, amino aciduria and phosphaturia), and the build-up of glycogen in the liver in a similar manner as seen in cases of glycogenesis type Ia. Due to the presence of liver glycogenosis, the patient also has a tendency towards hypoglycemia, ketonuria, hypercholesterolemia and hypertriglyceridemia. The glycogenosis seen in the patients with the Fanconi-Bickel syndrome, does not depend on a defect in the activity of the glucose-6-phosphatase enzyme, but in fact is due to a defect in the transporter which mobilizes glucose and galactose in the liver and in the basolateral membrane of the proximal tubule of the kidney. PMID- 1867747 TI - [The Pelger-Huet anomaly. A clinical and ultrastructural study of a family from northeastern Mexico]. AB - The Pelger-Huet anomaly is a benign disorder which affects the morphology of the granulocytes and is namely inherited as an autosomic dominant trait. The frequency of this anomaly varies from country to country and in Mexico this constitutes the sixth family reported. This is a case of a 21-month-old boy whose anomaly was detected during the study of his ferropenic anemia with which he arrived at the hospital. During the study of his nine family members, the anomaly was found to have also been present in his father. An electron microscopy study of the subject, his father's and a normal control's neutrophils was conducted. The patient's and his father's leucocyte granules were found to be normal but decreased in number. This work includes some discussion on inherited traits, their presentation, morphology, differential diagnosis and emphasizes the importance in recognizing this anomaly and the promotion of genetic counselling. PMID- 1867748 TI - [Cystic lymphangioma of the ileum. A case report]. AB - Cystic lymphangioma is an uncommon tumor of the small bowel. A case in the ileum in a 3 years old boy is described. The clinical picture was with 10 months of progression with constipation, abdominal pain associated with meals and finally an acute abdomen suggestive of appendicitis. A conservative surgical treatment with segmental intestinal resection and termino-terminal anastomosis was curative. The anatomopathological findings are described and a revision of the literature is done. PMID- 1867749 TI - [Periodontal disease in Noonan's syndrome]. AB - Two cases of non-related patients suffering from Noonan syndrome with characteristic data of the syndrome, had clinical and radiological evidence of very advanced periodontal disease. This disease seems to be unjustified because of the patients age and the lack of irritating local factors or systemic illnesses. A review of the literature showed no evidence of the periodontal disease as part of the syndrome. PMID- 1867750 TI - [Valproic acid in the management of Sydenham's chorea]. PMID- 1867751 TI - [A kidney from a friend: a transplant of greater acceptance]. PMID- 1867752 TI - Deficiencies in human neonates' color vision: photoreceptoral and neural explanations. AB - Several photoreceptoral and neural models have been proposed to account for the development of human vision. To further evaluate those applicable to color vision, the present study examined 40 neonates' (mean age = 3.2 days) chromatic achromatic discriminations in the mid-spectral region by using an habituation procedure and measures to minimize achromatic cues. Results indicated that newborns showed evidence of discriminating broad-band orange (lambda peak = 595 nm) but not yellow-green (lambda peak = 565 nm) lights from achromatic lights of varying luminance. Collectively, these and previous results imply that although newborns have at least dichromatic color vision, they possess relatively poor chromatic-achromatic discrimination in two spectral regions - in the short wavelengths (including stimuli of 470-480 nm) and in the mid-wavelengths (including 565 nm). Although several hypotheses were considered, newborns' chromatic 'neutral zones' are best accounted for by models proposing that early color vision is limited by a general inefficiency of preneural (photoreceptoral and optical) mechanisms and/or by a selective immaturity of the SWS cones or the B/Y opponent channel. PMID- 1867753 TI - Physical activity effects on hippocampal and parietal cortical cholinergic function and spatial learning in F344 rats. AB - In the present investigation, the effects of physical activity on hippocampal cholinergic function, parietal cortical cholinergic function, and spatial memory were examined in F344 rats. Single bouts of physical activity elevated hippocampal and cortical high affinity choline uptake, whereas chronic physical activity significantly reduced only hippocampal high affinity choline uptake (HACU) and elevated muscarinic (QNB) receptor density. Three weeks prior to the end of the 14-week chronic treadmill running protocol, a group of chronic-run rats and their non-run controls were tested on a stringent version of Whishaw's place learning-set task. Chronic-run rats exhibited enhanced performance on the spatial task by significantly reduced second trial latencies and elevated first and second trial proximity ratio scores. Chronic-run spatial memory tested rats also showed enhanced hippocampal HACU and muscarinic receptor binding. These data indicate that chronic physical activity improves spatial learning performance. This improvement may be due, in part, to a chronic running-induced enhancement of hippocampal cholinergic functioning. PMID- 1867754 TI - Short light-dark cycles influence sleep stages and EEG power spectra in the rat. AB - To investigate the influence of light on sleep and the electroencephalogram (EEG), chronically implanted rats were continuously recorded during a baseline day under 12-h light-12-h dark (LD 12:12) conditions, and an experimental day with short LD (LD 1:1) cycles. The percentage of non-REM sleep (NREMS) was higher and the percentage of REM sleep (REMS) lower in the 1-h light [corrected] intervals than in the 1-h dark intervals. The maximum of NREMS induction by 1-h light occurred in the habitual 12-h dark period (activity period), while the largest enhancement of REMS by 1-h darkness occurred in the second half of the habitual 12-h light period (rest period). The EEG of waking, NREMS and REMS was subjected to spectral analysis to determine the power density of the frequency components in the range of 0.25-25.0 Hz. The overall 24-h time course of the EEG spectra in NREMS was similar under baseline and experimental conditions. Nevertheless, the spectra were modified by the short LD-cycle. In NREMS, the values in the middle and high frequencies (greater than 6 Hz in the rest period; greater than 11 Hz in the activity period) were lower in the 1-h light intervals than in the 1-h dark intervals. In contrast, activity in some frequency bands during waking and REMS was higher in the light than in the dark intervals. It is concluded that the short LD-cycle modulates the vigilance states and induces state-specific changes in the EEG, whereas circadian aspects of sleep are little affected. PMID- 1867755 TI - Telencephalic but not diencephalic noradrenaline depletion enhances behavioural but not endocrine measures of fear conditioning to contextual stimuli. AB - Three experiments investigated the effects of primarily cortical or hypothalamic noradrenaline depletion on aversive conditioning of explicit and contextual stimuli in rats. In Expt. 1, two groups of rats were trained to respond under a variable interval schedule for food reward. One group of rats subsequently received injections of 6-hydroxydopamine into the dorsal noradrenergic bundle, resulting in profound depletion of cortical noradrenaline; the second group received vehicle injections. All rats were exposed to 5 pairings of an auditory stimulus (CS) and footshock (UCS) in a distinctive environment (the dark chamber of a place preference apparatus). During testing in a separate, neutral environment, DNAB-lesioned rats suppressed responding for food reward, in the presence of the aversive CS, to a greater degree than controls. Lesioned rats also showed a greater aversion to the distinctive environment in which they were shocked. In contrast, plasma corticosterone concentrations, measured immediately following each of these behavioural tests, revealed no differences between DNAB lesioned and control rats. Expt. 2 showed that the DNAB lesion did not affect habituation to the light chamber of the place preference apparatus used in Expt. 1. Expt. 3 showed that 6-OHDA injection into the ventral noradrenergic bundle component of the central tegmental tract, which damages primarily the noradrenergic innervation of hypothalamus, had no effect on either behavioural or endocrine responses to conditioned aversive, explicit or contextual cues. The results are discussed in relation to other reports of the effects of DNAB lesions on simple associative learning in an aversive context. PMID- 1867756 TI - Chronic oral treatment with diltiazem or verapamil decreases isolation-induced activity impairment in elevated plus maze. AB - Adult male Wistar rats were either socially isolated or group-housed for 6 weeks and then tested in an elevated plus maze. During isolation the rats received either water or two concentrations of the calcium channel inhibitors, diltiazem or verapamil, in drinking solutions (approximately 5 and 10 mg/kg daily). Isolated rats showed a significantly lower total number of arm entries, a lower percentage of open arm entries and negligible time spent therein than did group housed animals. Verapamil, in the higher dose, prevented that effect of isolation. Treatment with diltiazem brought about a similar tendency, though the effect did not reach statistical significance. Chronic treatment of group-housed rats with either drug failed to influence their behavior in the plus maze. We conclude that certain calcium channel inhibitors may decrease the behavioral deficit in the elevated plus maze that follows chronic social isolation. PMID- 1867757 TI - Sex-dependent effects of aversive stimulation on holeboard and elevated plus-maze behavior. AB - The behavioral effects of exposure to inescapable shocks (IS) were studied in both the holeboard and the elevated plus-maze, 24 and 72 h after IS in male and female Wistar rats. The following effects were observed at the 24-h interval. In both sexes, head-dipping in the holeboard was reduced by IS, whereas general activity (ambulation and rearing) was reduced in males and not in females. Furthermore, the results of a correlation analysis indicate that previous exposure to IS disrupts the dissociation observed in control groups between exploratory activity directed at the holes (head-dipping) and general activity in the holeboard (ambulation and rearing). Effects of IS on plus-maze behavior could be observed in a clear suppression of rearing in males and not in females. IS did not affect time spent on the open arms. At the 72-h interval, IS affected head dipping in the holeboard only in males and not in females. The present findings show that the effect of IS on specified behavioral elements is sex-dependent, with stronger and longer-lasting effects in males than in females. PMID- 1867758 TI - The acquisition of self-stimulation of the medical prefrontal cortex following exposure to escapable or inescapable footshock. AB - The effect of acute stress on the acquisition of an instrumental action reinforced by electrical stimulation of the medial prefrontal cortex (MPC) was investigated by exposing rats to either escapable, inescapable or no footshock prior to daily self-stimulation training sessions. Treatment with inescapable footshock did not affect the number of sessions required for acquisition of MPC self-stimulation but did increase the rate of responding over acquisition sessions compared with the no-shock group. When the treatment footshock was escapable, however, both a facilitation in acquisition, as indexed by a reduction in the number of sessions to criterion, and an increase in the rate of MPC self stimulation was found. These data were interpreted as offering evidence for the operation of a dopaminergic mechanism in the acquisition of MPC self-stimulation. Further, they indicate, contrary to the reported effects of footshock on self stimulation of other brain areas, that exposure to acute stress has a facilitatory effect on the rate of self stimulation of the MPC. PMID- 1867759 TI - Subcutaneous injection of carbachol enhances brain graft-induced recovery of memory-function by circumventing the blood-brain barrier. AB - After bilateral neurotoxic hippocampectomy adult rats received bilateral fetal suspension grafts at the lesion sites. Functional efficacy of fetal grafted tissue was substantially improved by subcutaneous administration of carbachol at a dose of 0.01 mg/kg s.c. The drug caused an almost complete restitution of performance in grafted animals in a Morris water-maze test. The progress of behavioral recovery was studied over 3 months postoperatively. Grafts of fetal hippocampal neurons alone improved lesion-induced spatial learning deficits to a limited degree. These results suggest that peripheral administration of carbachol may be of use in the treatment of central lesions associated with cognitive impairments, allowing or enhancing the development of graft-induced amelioration of behavioral deficits. The data also support the view that grafts of embryonic neural tissue may produce a local opening of the blood-brain barrier allowing drugs which normally act only peripherally to exert central effects. These central effects are probably limited to the graft site because the rest of the brain has a blood-brain barrier which is still intact. PMID- 1867760 TI - Completing the split in the split-brain rat: transection of the optic chiasm. AB - We describe a stereotaxic technique to transect the optic chiasm in the rat and present illustrative data on the interocular transfer of visual discrimination in chiasm-sectioned and chiasm-plus-forebrain commissure-sectioned animals. Applications of the technique are discussed. PMID- 1867761 TI - Brown (BAT) and white (WAT) adipose tissue in high-fat junk food (HFJF) and chow fed rats with dorsomedial hypothalamic lesions (DMNL rats). AB - Male weanling rats received dorsomedial hypothalamic nucleus lesions (DMNL) or sham operations and were fed for 173 postoperative days a high-fat diet and given a 32% sucrose solution as drinking fluid. This was supplemented with chocolate chip cookies, potato chips and marshmallows. Other DMNL and sham-operated controls were fed lab chow instead of the above high-fat junk food diet (HFJF) and given tap water instead of 32% sucrose solution. All animals were killed on postoperative day 174. Caloric intake per 100 g body weight was similar in all groups; however, the HFJF fed control and DMNL rats had significantly elevated carcass fat. Since HFJF-DMNL rats were not nearly as obese as the HFJF control animals, it appears that the DMNL offered some protection against the HFJF-diet produced obesity. When their smaller body size is considered. DMN lesions had no effect on brown adipose tissue (BAT) mass in chow-fed or HFJF fed rats, whereas BAT size was significantly enlarged in HFJF-fed control animals. This suggests but does not prove that HFJF-fed controls, but not DMNL rats, may be using dietary-induced thermogenesis (DIT) to attenuate their obesity. We hypothesize that the HFJF-fed DMNL may not be enhancing DIT as reflected in normal BAT size, because they had not attained a degree of fatness to activate this system, or the DMN lesions impaired its activation. Both HFJF-fed groups showed reduced linear growth compared to their counterparts. The reason for stunting is uncertain, but may be related to their low plasma insulin concentrations. PMID- 1867762 TI - Spatial and non-spatial spontaneous alternation and hippocampal mossy fibre distribution in nine inbred mouse strains. AB - Ten male mice from each one of nine inbred strains were tested for spontaneous alternation in a T-maze, which was placed in a spatially richly structured room. Each test consisted of two trials, the first choice to be made was forced, the second one free. By turning the maze 180 degrees between choices during 8 of the 16 tests, 3 variables could be measured: total alternation, spatial alternation, and non-spatial alternation. After Timm's staining, the sizes of the intra- and infrapyramidal mossy fibre terminal fields (iip-MF) were measured. Significant strain differences were found for all variables, but none of the behavioural variables correlated with hippocampal variation. These results disagree with earlier experiments, where large correlations between the iip-MF and spatial working memory were found. Some hypotheses to explain this discrepancy are presented. PMID- 1867763 TI - Behavioural differences between artificially selected aggressive and non aggressive mice: response to apomorphine. AB - The present study reports a first attempt to unravel the neurochemical background that underlies the difference in behavioural profiles between aggressive and non aggressive male mice. For this purpose two bidirectionally selected lines for attack latency (SAL and LAL) were used. In pursuit of Cools'9 approach, the susceptibility of individuals of both selection lines to the dopamine agonist apomorphine was measured. The apomorphine was injected subcutaneously at dose levels of 2.5 and 5.0 mg/kg. Apomorphine is considered to stimulate the dopamine receptors in the telencephalon and induces stereotyped behaviour. The responsivity to apomorphine can be rated as a total stereotypy-score. SAL (aggressive) mice showed a significantly greater enhancement of stereotyped behaviour in response to apomorphine than LAL (non-aggressive) mice. In addition, it was demonstrated that this difference is of a quantitative rather than qualitative character. Pharmacokinetic variation between the two lines could be ruled out as cause of the difference. Hence, it was concluded that SAL mice are more sensitive to apomorphine than LAL males, which provides evidence for a difference in the dopaminergic system between the two selection lines. It was suggested that this difference underlies the difference in flexibility in behaviour between aggressive and non-aggressive male mice. PMID- 1867764 TI - The chlamydial pneumonias. PMID- 1867765 TI - Intraocular infections: current therapeutic approach. PMID- 1867766 TI - Bronchiectasis: a current view. PMID- 1867767 TI - Human immunodeficiency virus (HIV)-associated pneumocystosis. PMID- 1867768 TI - Infection of burn wounds: evaluation and management. PMID- 1867769 TI - Colonic diverticulitis: microbiologic, diagnostic, and therapeutic considerations. PMID- 1867770 TI - Echocardiography in the management of patients with suspected or proven endocarditis. PMID- 1867771 TI - Echinococcal disease. PMID- 1867772 TI - The epidemiology of AIDS: a decade of experience. PMID- 1867773 TI - Genes directly involved in the biosynthesis of beta-lactam antibiotics. AB - Several genes encoding enzymatic activities involved in penicillin and cephalosporin biosynthesis have been identified. The first two steps in the biosynthesis of both antibiotics are common in penicillin, cephalosporin and cephamycin producers: condensation of the three precursor amino acids to form the tripeptide delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine, and oxidative cyclization of the tripeptide to form isopenicillin N. The genes involved in the two steps are pcbAB and pcbC respectively. The conversion of isopenicillin N to penicillin G is carried out by the enzyme isopenicillin N:6-APA acyltransferase encoded by the gene penDE. The biosynthesis of cephalosporin diverges from that of penicillin G at the isopenicillin N level. The isopenicillin N is first isomerized to penicillin N by an epimerase that is encoded by the gene cefD. The penicillin N is converted in deacetoxycephalosporin C by an expansion of the five membered thiazolidine ring to the six-membered dihydrothiazine ring. The deacetoxycephalosporin C is finally converted into cephalosporin C by a hydroxylation and O-acetylation. The enzymes which catalyze these last three steps are encoded by the genes cefE, cefF and cefG. The penicillin, cephalosporin and cephamycin biosynthetic genes are organized in clusters (and subclusters) of genes. PMID- 1867774 TI - Isolation and characterization of Rhizobium meliloti mutants affected in exopolysaccharide production. AB - Rhizobium meliloti mutants affected in the production of exopolysaccharide (EPS) were isolated after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. The mutants were classified into three phenotypic classes: (I) Exo-, rough mutants lacking exopolysaccharide; (II) Exos (for "small") which form tiny, compact colonies and synthesize reduced amounts of EPS; and (III) Exoc (for "constitutive"), hypermucoid mutants which overproduce EPS. Hypermucoid strains showed increased resistance to desiccation. All the mutants were able to nodulate, although a significant decrease in infectivity degree and/or competitiveness was found in rough and compact strains. Two mutants proved to be deficient in nitrogen fixation. Complementation analysis with cloned R. meliloti exo genes could not be applied to the study of these Fix- mutants because introduction of plasmids derived from cosmid vector pLAFR1 caused loss of nodulating ability. However, complementation of calcofluor staining and EPS production was observed. Complementation with certain exo genes also caused a marked increase in motility. PMID- 1867775 TI - [Serotypes of Salmonella enterica in sewage effluent from Zaragoza. Comparison with clinical isolates. 1982-1989]. AB - Between 1982 and 1989, 560 Salmonella enterica strains belonging to 63 serovars, were isolated from Zaragoza urban sewage. During the same period of time there were 45 different serovars isolated from faeces of patients from a hospital (in the same city). Only a reduced number of serovars comprised the majority of the human and environmental isolates. An approximately rectilinear relationship is shown between the isolated strains number and the number of different serovars, in non human Salmonella strains. In clinical isolates, we have not found this relation. We have compared the local results with those reported in other different Spanish regions. PMID- 1867776 TI - Numerical taxonomy of moderately halophilic gram-positive cocci isolated from the Salar de Atacama (Chile). AB - A taxonomic study has been carried out on 22 strains of moderately halophilic motile cocci isolated from the Salar de Atacama (Chile). The 112 phenotypic tests were analyzed by numerical taxonomy using SSM coefficient and the unweighted pair group method of association (UPGMA). At the 67% similarity level, two phenons were obtained: phenon A included 11 strains and phenon B, 11 strains too, whereas the six reference strains did not cluster within these two phenons. These results suggest that moderately halophilic cocci with different phenotypic characteristics from previously described species can be isolated from the hypersaline habitat Salar de Atacama. PMID- 1867777 TI - On the role of trehalose in yeast cells subjected to hypersomotic shock. AB - Plate counts on both high and low water activity (aw) media were performed during the growth of Candida utilis in batch culture. The results revealed a marked discrepancy between the counts on the two media in the logarithmic phase. The discrepancy almost disappeared in stationary phase revealing a higher resistance of these cells, as compared to growing cells, to the severe dehydration imposed by the hyperosmotic shock upon transfer to low aw medium. Since the two types of cells differ in the level of endogenous trehalose the relation between plating discrepancy and trehalose content of the cells was investigated. Treatments that changed the intracellular trehalose concentration did not modify the plate counts on low aw medium. It was therefore concluded that the amount of trehalose into the cells is not the only factor conferring resistance against the hyperosmotic shock. Glycerol content did not correlate with resistance to the water stress either. Congruent with the former conclusion, other yeast species (Sporobolomyces salmonicolor, Schizosaccharomyces pombe) showed no correlation between changes in the trehalose content and susceptibility or resistance to the osmotic stress in low aw medium. PMID- 1867778 TI - [Evaluation of the Autoscan-4 System for the identification of strains of the genus Salmonella]. AB - A study was performed to compare the Autoscan-4 with conventional biochemical methods to identify isolates of the Salmonella genus. The Autoscan-4 yielded correct identification of the 99% Salmonella isolates at the genus and species level, but failed to identify 74% Salmonella isolates of the "Arizona" group, making necessary to perform subspecies biochemical reactions. PMID- 1867779 TI - Comparison of quantitative analytical methods in evaluating acidophilic iron- and sulphur-oxidizing microorganisms liquid cultures. AB - Different quantitative methods to evaluate cell concentrations in acidophilic iron- and sulphur-oxidizing microorganisms liquid cultures have been compared with the "most probable number of viable germs" procedure. Plating and colony counting on recently developed solid media give good results when used with pure bacterial cultures, but plating efficiency decreases with natural mixed cultures. PMID- 1867780 TI - Pharmacotherapy in dentistry: macrolide antibiotics. PMID- 1867781 TI - Controlled drug release in periodontal therapy. PMID- 1867782 TI - Care and maintenance of dental curing lights. PMID- 1867783 TI - Smile designer's workshop. 3. Design theory of maxillary cuspids. PMID- 1867784 TI - The benefit-risk of dental implants: informed consent. PMID- 1867785 TI - The American dental laser: initial patient response. PMID- 1867786 TI - Hidden clasp partial denture. PMID- 1867788 TI - When to increase staff. PMID- 1867787 TI - Focusing on the big picture. PMID- 1867789 TI - Pharmacotherapy in dentistry: tetracyclines. PMID- 1867790 TI - The insurance game. PMID- 1867791 TI - Tooth-colored bonded posterior restorations: aesthetic alternatives to amalgam and gold. PMID- 1867792 TI - A new laser for endodontic and hard tissue applications. PMID- 1867793 TI - Devices ease endodontics. PMID- 1867794 TI - Comprehensive cosmetics: bridging the gap between traditional and cosmetic procedures. PMID- 1867795 TI - The twin block technique. PMID- 1867796 TI - The new periodontal diagnostics: commercial applications. PMID- 1867797 TI - Developing a comprehensive soft tissue management program. PMID- 1867799 TI - The major financial weaknesses of a dental practice: practical solutions. PMID- 1867798 TI - Marketing laser dentistry. PMID- 1867800 TI - Maximize your market share through effective case presentation. PMID- 1867801 TI - Expert systems: computers in dentistry. PMID- 1867802 TI - FDA panel says amalgam is safe; urges more studies to ease public fear. PMID- 1867803 TI - Anatomical considerations for mandibular implant surgery. 1. Specific anatomy introduction. PMID- 1867804 TI - A lingual medi-quiz. PMID- 1867805 TI - Broken posts: frustration or fulfillment. A new technique for removal. PMID- 1867806 TI - What is comprehensive soft tissue management? 2. Clinical aspects. PMID- 1867807 TI - Interceptive preprosthetic oral surgery envisioned for the perceptive dentist. PMID- 1867808 TI - Pharmacotherapy in dentistry: cephalosporin antibiotics. PMID- 1867809 TI - A clinical case illustrating a new implant abutment. PMID- 1867811 TI - OSHA update: what you need to know about an OSHA inspection. PMID- 1867810 TI - The future of amalgam; what can take its place? PMID- 1867812 TI - Smile designer's workshop. 4. Design theory of maxillary premolars. PMID- 1867813 TI - Indirect resin inlays: all the benefits without the disadvantages. PMID- 1867814 TI - Thirteen steps to a perfect impression. PMID- 1867815 TI - Pharmacotherapy in dentistry: quinolones. PMID- 1867817 TI - Anatomical considerations for mandibular implant surgery. 2. Two common post operative problems. PMID- 1867816 TI - Uses and features of intraoral video camera systems. PMID- 1867818 TI - Endodontic diagnosis. PMID- 1867819 TI - The insurance game: periodontics. PMID- 1867820 TI - Implants and cosmetic dentistry. PMID- 1867821 TI - Become more efficient with a light communication system. PMID- 1867822 TI - Dental team members: why they act the way they do! PMID- 1867823 TI - Instilling behavior management in children and parents. PMID- 1867824 TI - How to maintain the endosseous implant. PMID- 1867825 TI - The "Spider from Mars" resilient resin-bonded bridge. PMID- 1867826 TI - Smile designer's workshop. 5. The role of gender in smile design. PMID- 1867827 TI - The insurance game: removable prosthodontics. PMID- 1867828 TI - "Alpha" gutta-percha--is it just another phase? PMID- 1867829 TI - Reviewing auxiliary performance and salary. PMID- 1867830 TI - Applying today's technology. Monitoring and detecting progressive periodontitis. PMID- 1867832 TI - Hidden clasp partial is a viable option. PMID- 1867831 TI - Partial dentures: they still have a place in dentistry. PMID- 1867833 TI - Treating the emergency dental trauma patient. PMID- 1867834 TI - Establishing a sound financial policy: how to ask for money, collect it, and still feel comfortable. PMID- 1867835 TI - Central action of benserazide after COMT inhibition demonstrated in vivo by PET. AB - Positron emission tomography (PET) following intravenous administration of beta [11C]-L-DOPA provides a method of assessing regional cerebral uptake and utilization of levodopa. Cerebral levodopa kinetics in the rhesus monkey were investigated after the inhibition of catechol-O-methyltransferase (COMT) with RO 40-7592, and after coadministration of the peripheral aromatic L-amino acid decarboxylase (AADC) inhibitors benserazide and carbidopa. Pretreatment with RO 40-7592 (10 mg/kg), benserazide (10 mg/kg) or carbidopa (3.5 mg/kg) did not change striatal k3, which mainly reflects the ability for the brain tissue to convert [11C]-L-DOPA to [11 C]-dopamine, although the brain's uptake of radioactivity increased substantially after pretreatment with the AADC inhibitors. When benserazide was coadministered with RO 40-7592 (10 mg/kg) a dose dependent decrease in striatal k3 was measured with an apparent ED50 of 3 mg/kg. No such effect was indicated after pretreatment with the combination of RO 40 7592 (10 mg/kg) and carbidopa (3.5 mg/kg). The possible negative interactions of coadministration with COMT inhibitors and predominantly peripherally acting AADC inhibitors must be considered when used in the therapy of Parkinson's disease. PMID- 1867836 TI - Changes in cholinergic and opioid receptors in the rat spinal cord, dorsal root and sciatic nerve after ventral and dorsal root lesion. AB - Changes in the distribution of 3H-quinuclidinylbenzilate (3H-QNB), 3H acetylcholine (3H-ACh) and 3H-alpha-bungarotoxin (alpha-BTx) binding sites were studied with the use of quantitative in vitro autoradiography in the L4-L6 segments of rats 7 days after ventral L4-L6-rhizotomies and 24 hours after ligation of the dorsal roots L4-L6. The changes in the binding sites of these ligands and of 3H-etorphine binding sites were also studied in the dorsal roots of the rats operated with dorsal root ligation and in the sciatic nerves (around a ligature) in the rats operated with ventral rhizotomy. After ventral rhizotomy 3H-QNB binding sites in the ipsilateral motor neuron area were decreased by about 25% from 100 +/- 5 to 73 +/- 5 fmol/mg wet weight. After dorsal root ligation 3H QNB binding sites in the ipsilateral posterior horn were reduced by about 30% from 91 +/- 5 to 64 +/- 7 fmol/mg wet weight. No significant changes in the binding of the other cholinergic ligands in the spinal cords were observed after the operations. In the dorsal root 3H-alpha-Btx and 3H-etorphine binding sites were higher on the distal side of the ligation (3.5 +/- 0.8 and 14 +/- 4 fmol/mg wet weight, respectively) than on the proximal side (0.7 +/- 0.5 and 2.4 +/- 1.2 fmol/mg wet weight, respectively). The same level of 3H-ACh (total, muscarinic and nicotinic) binding was observed on both sides of the ligation. In the sciatic nerve 3H-QNB and total, muscarinic and nicotinic ACh binding sites were higher on the proximal side of the ligation than on the distal side.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867837 TI - Hypothalamic luteinizing hormone-releasing hormone content and serum luteinizing hormone levels in male rats during wallerian degeneration of sympathetic nerve terminals after superior cervical ganglionectomy. AB - The main hypothesis of this study was that sympathetic neurons located at the superior cervical ganglia (SCG) control luteinizing hormone (LH) releasing mechanisms by acting at a hypothalamic site. To test this, medial basal hypothalamus (MBH) luteinizing hormone-releasing hormone (LHRH) content and serum LH levels were measured in male rats subjected to superior cervical ganglionectomy (SCGx) or sham-operation 14 or 38 h earlier, at the time of degeneration of nerve endings post-SCGx. Significantly augmented MBH LHRH levels and decreased circulating LH were found in SCGx rats. In animals subjected to SCGx 14 h earlier and receiving a single injection of the alpha 1-adrenergic blocker prazosin, the beta-adrenergic blocker propranolol or a mixture of both drugs 45 min before sacrifice, only the injection of prazosin prevented the decrease of plasma LH levels. Neither treatment prevented the increase in MBH LHRH content. When prazosin was given every hour starting from the 10th to the 13th h after surgery, it was effective to prevent both the increase of MBH LHRH content and the decrease of serum LH found during sympathetic nerve degeneration. Similar repetitive injections of propranolol resulted in the greatest depression of serum LH, and in the greatest increase of MBH LHRH observed. Serum LH response to LHRH injection was similar in SCGx and sham-operated rats. The data indicate that SCG neurons exert, through inhibitory alpha 1-, and weaker, stimulatory beta adrenoceptors, a significant influence on LHRH release at a supra-hypophysial site. PMID- 1867838 TI - Urinary elimination of salsolinol enantiomers in alcoholics. AB - The analysis of the urine from 6 chronic alcoholics showed that (R)- and (S) salsolinol were detectable in 4 subjects, the R enantiomer was only found in one and that both enantiomers were under the limit of detection in another one. 1,2 Dehydrosalsolinol was present in the urine of all of them. There was no correlation between the presence of alcohol in blood upon admission to the hospital and that of either salsolinol enantiomer in urine In a previous study (Strolin Benedetti et al., 1989 b), both salsolinol enantiomers were found in the urine of 3 out of 6 healthy subjects, possibly in relation with regular intake of alcoholic beverages. The content in (R)- and (S)-salsolinol was determined in the same 3 subjects after deprivation of alcohol for 24 h. Under these conditions, only (R)-salsolinol was detected in urine and this also after ingestion of 50 g of alcohol (500 ml Chianti). The possible involvement of the non-physiological enantiomer of salsolinol in alcohol addiction deserves further study. PMID- 1867839 TI - The effects of shifting sleep two hours within a fixed photoperiod. AB - This study examined the effects of shifting the time of sleep within a constant photoperiod on the circadian rhythms of body temperature and melatonin secretion. Subjects lived under conditions of a long scotoperiod (dim light of less than 10 lux from 6 p.m. until 8 a.m.) for three weeks. In order to delineate dawn and dusk, subjects received one hour of bright light (2500 lux) before and after the scotoperiod (i.e., from 8 to 9 a.m. and from 5 to 6 p.m.). For the first week of the experiment they slept from 10 p.m. until 6 a.m. In the second week, sleep was advanced two hours; that is, subjects retired at 8 p.m. and arose at 4 a.m. The third week was a repeat of the first, resulting in a two-hour delay of sleep from week two to three. The six subjects who successfully completed this protocol had no significant changes in the timing of the body temperature minima and onset of secretion of melatonin. This indicates that the timing of allowed sleep has less of an immediate effect on circadian rhythms than the timing of the external light dark cycle. The circadian effects of the timing of sleep may be due more to the light-dark cycle that is imposed by the sleep-wake cycle than from the timing of sleep itself. PMID- 1867840 TI - Synergistic interactions between the NMDA antagonist dizocilpine and the preferential dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 with regard to locomotor stimulation in monoamine-depleted mice. AB - When administered to mice pretreated with the monoamine-depleter reserpine and the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine, the preferential autoreceptor antagonists (+)-AJ76 and (+)-UH 232 induced weak locomotor stimulation. When either (+)-AJ 76 or (+)-UH 232 was combined with a subthreshold dose of the selective NMDA antagonist dizocilpine (MK-801), a marked locomotor stimulation was produced in monoamine-depleted mice. The mechanism of this stimulation, although reduced by dopamine antagonists, remains to be clarified. PMID- 1867841 TI - [Blood alcohol concentration and effect, traffic medicine characteristics and legal traffic relevance of alcohol limit values in road traffic]. AB - Since the expert report of the Federal Health Office (FHO) in 1966 (also compare FHO expert report 1977) numerous papers about the influence of small doses of alcohol on driving ability have been published (see Blood Alcohol, Alcohol, Drugs and Behavior). These papers emphasise the possibility to prove an acute influence on the central nervous system of man with characteristic consequences for his readiness to perform and his general effectiveness with regard to the safe conduct of a vehicle above a concentration of blood alcohol from 0.2 to 0.3% upwards. This experimentally observed increase in knowledge which conforms with jurisdiction i.e. assuming the possibility of alcohol-effected reduced driving ability above 0.3% in individual cases, -however, does not include a regular capability to detect a reduced driving ability for a range in blood alcohol concentration of 0.3% to 1.0% (see opinion of the directors and boards in the German Society for Legal Medicin, 1984). From All presentations the following conclusions may be drawn regarding the level and traffic medicals als well as psychophysical relevance and the forensic importance of alcohol threshold values in road traffic: 1. The 0.0% would be consistent. Each trace of blood alcohol can influence driving ability. Such a limit would, however, be linked to an intolerable cover-up-level. 2. The threshold level to prove the effect of alcohol lies at 0.3% to 0.4% as a basic value (jurisdiction = 0.3%). This level must definitely be regarded as preventing traffic accidents. FREUDENBERG, 1966: At 0.4% the relative probability to become involved a lethal traffic accident is 2.1 times higher than the sober value. BORKENSTEIN, 1964/74: At 0.4% the relative probability to cause an accident is not significantly higher than the sober value. A blood alcohol concentration of 0.4% may be proven by an analytical average value of 0.5% (safety margin: 0.1%). From legal and traffic medical viewpoint nothing contradicts the intention to establish an abstract danger ceiling at 0.4 + 0.1% = 0.5% linked to unlawful behaviour and the prohibition to drive. 3. The danger ceiling presently in operation contains a basic value of 0.6 to 0.7% and a safety margin of 0.15% = 0.8%. At 0.6 to 0.7% the majority of drivers are unable to participate in the traffic. FREUDENBERG, 1966: At 0.7% the relative possibility to become involved in an traffic accident is 3.7 times higher als compared to the sober value. BORKENSTEIN: At 0.7% the relative probability to cause an accident in increased 2.7 times.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1867842 TI - [Critical questions regarding standard deviation as a precision parameter of blood alcohol determination]. AB - The relative absolute standard deviation, which was introduced for the control of the precision of blood alcohol-determinations by the BGH reveals, that according to technical rules the admissible standard deviation in the range of higher blood alcohol concentrations is exceeded despite the fact, that the width of the variation is still in the acceptable range. The standard deviation of 0.05% should therefore only be applied to the blood alcohol range up to 1.5%. As an alternative the coefficient of variation can be chosen for the precision control. PMID- 1867843 TI - [Incorrect blood specimen collection for forensic blood alcohol determination]. AB - Blood to measure the level of bloodalcohol will be taken usually by tapping veins. Sometimes vessels are brought with blood diluted by other solvents. It is possible to determine bloodalcohol levels also in these cases. PMID- 1867844 TI - [Criteria for the validation of forensic breath alcohol tests (results of a specialty meeting of the Society against Alcohol in Road Traffic e.V.)]. AB - According to the conception developed in the Federal Health Office a forensic breath-alcohol determination requires two independent measurements of ethanol concentration received by two measuring systems of different analytical specify in order to detect interfering substances. In addition to the two values of the breath-alcohol concentration two values of the exhaled volume, the duration of exhalation and the final breath temperature were obtained. According to the recommendations of the Organisation Internationale de Metrologie Legale (OIML) valid measurements require two breath alcohol values. The difference between the two values must not exceed prescribed limits. Furthermore the other pairs of measured values can be used for a judgement of the measuring procedure. Criteria were derived from the results of tests in practice. By application of these criteria the reliability of breath-alcohol determination is increased and an influence intentioned by the subject on measured values can be avoided. PMID- 1867845 TI - [Blood alcohol in relation to the presence of n-butyl acetate]. AB - Adult female SPF rats (strain: Sprague-Dawley) were treated with 790 mg ethanol/kg body weight by intraperitoneal injection 30 minutes after the beginning of a 5-hr-inhalation of about 1,000 ppm n-butyl acetate in air via a tracheotomy tube (under urethane anesthesia). The elimination of the ethanol from blood which was increased to about 24 mmol/l (1.1%, g/v) was not delayed during the initial linear phase as compared to control (ethanol treatment without inhalation of n-butyl acetate). During inhalation approximately 24 mumol n-butyl acetate/l were measured in blood without ethanol treatment and approximately 52 mumol n-butanol/l as a metabolite of n-butyl acetate. The n-butanol content in blood was doubled under ethanol treatment. This increase is explained by substrate competition of both alcohols at the alcohol dehydrogenase with ethanol excess. PMID- 1867846 TI - [Offenses in alcoholic intoxication with reference to American research]. PMID- 1867847 TI - Oligonucleotide purification in milligram quantities. AB - An inexpensive and simple procedure for the purification of synthetic oligonucleotides is described. Hands-on time is only 30 to 40 minutes and multiple samples can be prepared simultaneously. One- to two-milligram quantities can easily be handled by a single column with no further purification required for the DNA to be used in a wide variety of molecular biological uses. PMID- 1867848 TI - Reduced chloramphenicol acetyltransferase activity observed with vectors containing an upstream SphI recognition sequence. AB - Chloramphenicol acetyltransferase (CAT) is the most commonly used reporter gene for studying the regulation of mammalian gene transcription. Some of the currently available CAT vectors contain the recognition sequence for the restriction endonuclease SphI within the multiple cloning site. This sequence introduces an ATG triplet that is out of frame with the initiation codon of the CAT gene. Transient expression of CAT fusion genes, constructed using three different cellular promoters, demonstrates that the presence of the upstream AUG triplet in the CAT transcript reduces CAT activity, presumably by interfering with the translation of the coding sequence. Deletion of the SphI site from each of the plasmids increased CAT activity between 4-fold and 5-fold. From these results, we conclude that upstream, out-of-frame ATG triplets must be avoided in order to achieve maximum expression of the reporter gene. PMID- 1867849 TI - S1 nuclease transcript mapping using sequenase-derived single-stranded probes. AB - We report here a simple method for the production of high specific activity single-stranded DNA probes for S1 nuclease transcript mapping. Plasmid DNA is used as in vitro DNA templates for probe production by primer extension using Sequenase. This allows the production of long single-stranded probes without the need to subclone restriction fragments into M13 vectors. The mapping of the 5' ends of the phage P1 mod gene transcripts is shown as an example. PMID- 1867850 TI - Temperature recording from thermocyclers used for PCR. AB - Using a simple electronic circuit, a thermocouple can be connected to a chart recorder to measure the actual temperature inside a PCR tube. This allows accurate inspection of the thermocycle program and comparison between thermoprofiles from different thermocyclers. We found that the recording of temperature cycling enabled us to obtain more reliable and reproducible results. PMID- 1867851 TI - Use of UV irradiation to reduce false positivity in polymerase chain reaction. AB - UV irradiation provides a simple and efficient way to minimize contamination or false positivity which often occurs in laboratories performing routine PCR tests. Here, we characterize several parameters of the effect of UV irradiation on DNA template, primers, deoxynucleoside triphosphate and Taq polymerase. UV irradiation of DNA results in the formation of pyrimidine dimers and thus prevents them from being effective templates in subsequent PCR. Reduction of the HIV DNA templates in polypropylene microcentrifuge tubes by more than 1000-fold can be achieved by UV irradiation. The sensitivity of the primers is sequence- and concentration-dependent. Oligonucleotides with neighboring thymine bases are more susceptible to UV than those without. Taq polymerase is highly UV sensitive, whereas deoxynucleotide triphosphate is relatively UV resistant. PMID- 1867852 TI - Subnanomole detection and quantitation of high specific activity 32P-nucleotides. AB - Microbore liquid chromatography utilizes conventional HPLC and ultraviolet detection principles to determine subnanomole mass quantities of biologically significant molecules. This system takes advantage of specifically designed microflow equipment to analyze ultraviolet absorbing species at the picomole range. 32P-labeled nucleotides are examples of compounds routinely used at picomole quantities that are extremely difficult to accurately quantify using standard mass measurement techniques. The procedure described in this paper has the capability of measuring nucleotides down to 10 pmol using commercially available microbore ultraviolet detection equipment. The technique can be used to accurately measure the specific activity of as little as 10 microCi of an aqueous 32P-nucleotide solution. PMID- 1867853 TI - A centrifugation method for the isolation of plasmid DNA without the use of an ultracentrifuge. AB - This paper describes the use of a high-performance high-speed centrifuge, a Sorvall RC-28S, for the preparation of plasmid DNA using standard CsCl-ethidium bromide gradients. If the sample is layered into the bottom of the gradient, the plasmid DNA can be banded in 24 hours; this is comparable with the time required for ultracentrifuge separations. Alternatively, plasmids can be banded in a fixed angle rotor in 36 hours when the sample is mixed throughout the gradient solution. PMID- 1867854 TI - Subcloning with new ampicillin- and kanamycin-resistant analogs of pUC19. PMID- 1867855 TI - Rapid identification of specific genes in E. coli by hybridization to membranes containing the ordered set of phage clones. AB - A simplified protocol for the hybridization of labeled oligonucleotides and other radiolabeled DNAs to membranes is described and used for the detection of specific recombinant phage in the ordered miniset collection representing virtually the entire E. coli genome. PMID- 1867856 TI - Generation of high efficiency, single-stranded DNA hybridization probes by PCR. PMID- 1867857 TI - Rapid identification of transfected plasmid expression vectors in cells by PCR. PMID- 1867858 TI - "Megaprimer" method of PCR: increased template concentration improves yield. PMID- 1867859 TI - Non-isotopical labeling of murine heterochromatin in situ by hybridization with in vitro-synthesized biotinylated gamma (major) satellite DNA. AB - Degenerate probe DNA, homologous to part of the 234-bp repeated mouse gamma (major) satellite DNA, was generated by primer-directed in vitro DNA amplification using the polymerase chain reaction with oligonucleotide primers that anneal in the most conserved parts of the repeat. Probe labeling with biotin was performed during DNA polymerization. In situ hybridization of probe DNA with metaphase chromosome preparations showed exclusive binding of probe molecules to the centromeric region of mouse chromosomes. We applied the probe DNA for labeling of mouse heterochromatin in metaphase chromosomes, as well as interphase cell nuclei, and compared results of probe visualization using avidin tagged with either fluorescein or alkaline phosphatase in combination with a chromogenic substrate. PMID- 1867860 TI - Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material. AB - Procedures utilizing Chelex 100 chelating resin have been developed for extracting DNA from forensic-type samples for use with the PCR. The procedures are simple, rapid, involve no organic solvents and do not require multiple tube transfers for most types of samples. The extraction of DNA from semen and very small bloodstains using Chelex 100 is as efficient or more efficient than using proteinase K and phenol-chloroform extraction. DNA extracted from bloodstains seems less prone to contain PCR inhibitors when prepared by this method. The Chelex method has been used with amplification and typing at the HLA DQ alpha locus to obtain the DQ alpha genotypes of many different types of samples, including whole blood, bloodstains, seminal stains, buccal swabs, hair and post coital samples. The results of a concordance study are presented in which the DQ alpha genotypes of 84 samples prepared using Chelex or using conventional phenol chloroform extraction are compared. The genotypes obtained using the two different extraction methods were identical for all samples tested. PMID- 1867861 TI - Automated image-based cytometry with fluorescence-stained specimens. AB - The combination of digitized microscopy, algorithms for object recognition and fluorescent labeling is a promising approach for reliable, quick, automated and cost-effective screening of clinical specimens. We describe two conceptually different algorithms for detecting objects in fluorescence microscopic images. One, which is partially automated, compares a mask that represents a typical object with every position in the image; the other, which is fully automated, calculates threshold intensities to segment the image into regions of objects and background. Applications of the algorithms in conjunction with a prototype image based cytometer are demonstrated for determining the DNA ploidy distribution of cultured human endometrial cells and determining the DNA ploidy distribution and the fraction of cells expressing the E6 antigen of human papilloma virus serotypes 16 and 18 in a PAP smear. The encouraging results from this study suggest that automated image-based cytometry utilizing fluorescent stains will be a valuable asset for clinical screening. PMID- 1867862 TI - A new cationic liposome reagent mediating nearly quantitative transfection of animal cells. AB - One of the most efficient systems for the expression of genes in the cytoplasm of animal cells utilizes a recombinant vaccinia virus encoding the bacteriophage T7 RNA polymerase. Cells infected with this virus are transfected with plasmid DNAs containing the gene to be expressed under T7 promoter control. The major limitation of this system is the efficiency with which DNA is introduced into the cell. Recently, a cationic liposome-mediated transfection reagent has yielded transfection frequencies of greater than 80%. To determine if commercially available cationic lipids could form liposomes that would yield similar transfection efficiencies, we tested liposomes prepared with five different cationic lipids. When used at appropriate concentrations in liposomes that also contained a neutral lipid, four of the five cationic lipids were effective in the transfection of HeLa cells. However, liposomes formed with the neutral lipid and one of the cationic lipids, dimethyldioctadecylammonium bromide (DDAB), gave transfection frequencies of greater than 95% and had a broad spectrum of effectiveness on a variety of cell lines. Liposomes containing DDAB are an inexpensive, highly efficient and reproducible alternative for the transfection of animal cells and are well suited for use with the vaccinia virus/T7 expression system. PMID- 1867863 TI - Temperature cycler evaluation: what do you need to know? AB - Which of the 20 different, commercially available, temperature cyclers adequately fulfill all functional requirements? How can an investigator analyze instrument function? This report describes in detail, for the first time, the characteristics of Ericomp temperature cyclers. The data show that the temperature uniformity, accuracy and maximum overshoot is +/- 0.34 degree C, less than 0.5 degree C and 0.17 degree C, respectively. Cycling temperature reproducibility is 0.1%, and cycling time reproducibility is 0.4%. These data compare very favourably to published data describing other temperature cyclers. The techniques used to obtain these data serve as a model for evaluating instruments for well-to-well uniformity, temperature accuracy and within-run reproducibility. PMID- 1867864 TI - An ectopic rim sign in hepatobiliary scintigraphy. AB - A 59-year-old man with gangrenous cholecystitis is presented along with an hepatobiliary scan that demonstrated nonvisualization of the gallbladder and a curvilinear area of increased activity in the region of the fissure for the ligamentum teres or common hepatic duct. There was no "rim sign" in the gallbladder fossa. We propose that perforation of the gallbladder and resultant pockets of pus may, through edematous compression of liver parenchyma, produce an ectopic rim sign if inflammation comes in contact with another portion of the liver. PMID- 1867865 TI - In vivo sodium-23 MRI in brain tumors: evaluation of preliminary clinical experience. AB - In vivo sodium-23 magnetic resonance (MR) imaging in the head was performed in ten normal volunteers and six patients with brain tumors on a commercially available 1.5 Tesla whole-body MR system. Although sodium MR signal from the brain parenchyma could hardly be detected on routine spin echo (SE) pulse sequence, free induction decay (FID) image with echo time of 1.9 msec demonstrated MR signal in the normal brain tissue. On the other hand, extracellular sodium of cerebrospinal fluid, large venous sinus, and vitreous humor offered high sodium MR signal intensity due to the quantity of sodium and the relatively longer transverse relaxation time (50-60 msec) compared to that of intracellular sodium (less than a few msec). Strong signal was obtained in gliomas with superior contrast, though the delineation of the tumor tissue from edema was as difficult as when seen on proton T2 weighted SE image. Meningioma itself gave much less of a sodium MR signal compared to glioma. Peritumoral edema associated with meningioma showed a markedly high sodium MR signal which was more prominent adjacent to the tumor, although proton SE image revealed the peritumoral edema as homogeneous. Pathological tissues such as brain tumors and edema could be readily depicted as significantly high sodium-23 MR signal, apparently different from normal brain tissues. The current status of in vivo sodium MR imaging is discussed. The authors concluded that early clinical experience of in vivo sodium-23 MR imaging brought promising results in the evaluation of brain tumors and edema; otherwise, discrimination and quantification of multiple T2 components and the improvement of spatial resolution are desperately needed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867866 TI - In vivo assessment of regional microvascular albumin leakage during E. coli septic shock in the baboon model. AB - Changes in regional microvascular albumin flux during septic shock were studied noninvasively by scintigraphy in the baboon model. Use was made of an i.v. injection of 99mTc-labelled baboon serum albumin. Count ratios of lung to cardiac, liver to cardiac, and abdominal to cardiac regions were measured every 2 hr for 6 hr in control and septic shock baboons, and compared. Increased ratios obtained during shock pointed to an increase in extravascular albumin. Linear regression lines fitted to these count ratios provided regional albumin leak indices. These indices demonstrated statistically significant increases (P less than 0.05) during septic shock for the abdominal region during the 6-hr study, and for all regions, but especially the abdomen, when data were calculated over 4 hr. Increasing ratios and leak indices correlated with postmortem data and changes in neutrophil and platelet behaviour previously established during shock. PMID- 1867867 TI - Use of indium-111-labeled transferrin to study plasma extravasation during endotoxin shock and the effects of the beta-2 agonist terbutaline. AB - Endotoxemia and sepsis are common causes of respiratory distress (ARDS), which is characterized by increased pulmonary vascular permeability to plasma proteins resulting in "noncardiac pulmonary edema." The aim of this series was to study the effects of the beta-2 receptor agonist, terbutaline, on plasma extravasation in multiple organs, in sheep exposed to endotoxin shock. A double isotope technique was used and the radioactivity was recorded in different organs (lungs, liver, spleen, kidneys, intestine) by a computerized gamma camera. Tc-99m-labeled erythrocytes were used as a marker for intravascular volume and In-111m-labeled transferrin for tracing extravascular plasma leakage. An organ-transferrin index (organ-TI) was calculated for each organ which corrects for changes in blood distribution. Fourteen sheep were anesthetized and ventilated. After stabilization (t = 0) all animals received E. coli endotoxin 10 micrograms/kg by IV infusion during 30 min. At t = 30, seven animals (group T) received IV infusion of terbutaline, 20 micrograms/kg/hr, during 4 h, while the other seven received normal saline and served as controls (group E). The endotoxin infusion caused an immediate and significant increase in the transferrin index in the lungs and in the liver in both groups. The transferrin index continued to rise in the control group towards the end of the experiment (t = 240), while in group T it reached a maximum 60 min after endotoxin. Four hours after endotoxin the transferrin index was significantly higher in the controls than in the terbutaline treated group, both in the lungs and in the liver (P less than 0.01). No significant changes were recorded in the kidneys or over the intestine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867868 TI - Physiological considerations in imaging of lower extremity venous thrombosis. AB - Lower extremity venous thrombosis is a major clinical problem because of its potential for pulmonary embolism and local vascular compromise. We present an anatomical and physiological overview followed by a review of current diagnostic methods and their underlying rationale. PMID- 1867869 TI - Effect of parental smoking on wheezy bronchitis and bronchial hyperreactivity. AB - In the course of the follow-up of 206 previously obstructive bronchitis children, the effect of parental smoking upon the occurrence of respiratory diseases, the yearly frequency of wheezing episodes and the age until the obstructive episodes used to return have been investigated. Familial and maternal smoking was more frequent in this group compared to the control group. In spite of this, however, no correlation could be detected between familial smoking and frequency of respiratory diseases, as well as the above mentioned characteristics of obstructive bronchitis. The familial smoking did not seem to influence the bronchial hyperreactivity challenged with acetylcholine, although the prevalence was higher. PMID- 1867870 TI - Prostacyclin and thromboxane levels of children of parents suffering from early ischemic heart disease. AB - Offsprings of parents who had acute myocardial infarction before age of 45 years were investigated. The aim of this examination was to obtain information whether the variation in the balance of prostacyclin/thromboxane ratio is a common cardiovascular risk factor in children. In children whose parents have had early myocardial infarction, a significant decrease was shown in 6-keto-prostaglandin F1 alpha level while the thromboxane B2/6-keto-prostaglandin F1 alpha ratio increased in these children. Plasma tromboxane B2 levels hardly differed from those of the control in that group of children whose one parent and at least one of the grandparents or uncles or aunts suffered from coronary heart disease. Plasma thromboxane concentration was lower in another group of children whose "only" one parent had myocardial infarction. It may be supposed that this is a compensatory mechanism in the offspring of parents suffering from early coronary heart disease. PMID- 1867871 TI - Physical health and behavioral problems in two high schools in Holon, Israel. AB - 1320 students of two high schools were examined in Holon. Their physical and behavioral problems are summarized. These data serve to build the model of the medical profile of the adolescent in Israel, as a background to medical screening in school, which should be done at least every two years. PMID- 1867872 TI - Familial occurrence of bilateral renal agenesis. AB - The 58 cases of bilateral renal agenesis (Potter syndrome) registered in the Genetic Counselling unit of our institute in the last 12 years are reviewed. The only familial recurrent case which has been prenatally diagnosed is described in detail. A urinary bladder anomaly like that of the subsequent third child has not been previously reported. The authors analyze the possible inheritance patterns. They suggest the malformation is a genetically heterogeneous entity. They emphasize that nowadays the birth of a newborn with bilateral renal agenesis can be prevented in all cases. PMID- 1867873 TI - Influence of some social and maternal factors on birth weight in Hungary. AB - In this study, we have examined the impact of some social and maternal factors on birth weight in the two regions Hungary, in the capital and in one county. Although many of the variables were analyzed in both regions, significant relationships were found between LBW and smoking habits, birth order and mother's age. The incidence of low birth weight was higher in Budapest than in Vas. Smoking habits were found as a common factor of higher significance in both regions. Birth order and mother's age were found as other factors of higher significance in the Budapest sample as compared to Vas. PMID- 1867874 TI - Burkitt's lymphoma with 3;14 and 2;8 translocations simultaneously. AB - Burkitt's lymphoma of a ten-year-old boy with specific 8;14 and variant 2;8 translocations is reported. The post mortem diagnosis of Burkitt's lymphoma was based on histological picture and the cytogenetic findings of the tumor biopsy. The child died four days after clinical admission. Because of the rapid progression of the disease immunological and serological investigations could not be performed. Therefore several questions remained unclarified. It is supposed that in the patient's B-lymphocytes multiple transformation events occurred leading to the development of the polyclonal lymphoma, similarly to that described in transplant-associated lymphoproliferations. PMID- 1867875 TI - Myelodysplasia in childhood. AB - Two simple statements can be given which reflect our helplessness with respect to myelodysplasia. MDS are rare in childhood, but features and course of disease resemble those in adults. JCMML should be considered as a pediatric subtype of MDS, but with a worse prognosis than CMML in adult patients. PMID- 1867876 TI - Postnatal development of urea- and ammonia-excretion in urine of very-low-birth weight infants small for gestational age. AB - In 12 very-low-birth-weight (VLBW) infants with intrauterine growth retardation and in 14 VLBW-infants appropriate for gestational age (AGA) fed a human milk (HM) formula (HM enriched with 6 g freeze dried HM per 100 ml) the renal excretion of urea and ammonia was studied on the 10th, 21st and 42nd days of life. The lowest excretion of urea was found in both groups on the 10th day of life. Up to the 42nd day of life the excretion raised significantly more in the AGA- than in the small for gestational age (SGA)-infants. In contrast to the urea excretion the excretion of ammonia was highest on the 10th day of life in both groups, but the excretion was significantly higher in the SGA-infants if compared to the AGA-infants. In the AGA-infants excretion of ammonia decreased with postnatal age whereas in the SGA-infants the high excretion remained up to the 42nd day of life. The data suggest that in VLBW-infants the urea synthesizing capacity is decreased and develops within the first weeks of postnatal life. The postnatal development is delayed in SGA-infants when compared to AGA-infants. The differences are more pronounced with increasing degree of intrauterine growth retardation. PMID- 1867877 TI - Transient hyperinsulinism in asphyxiated newborn infants. AB - Hypoglycemia in birth asphyxiated infants is attributed to glycogen depletion. We observed three term AGA (Appropriate for Gestational Age) infants with birth asphyxia, who developed hyperinsulinemic hypoglycemia postnatally. All had inappropriately high serum insulin concentrations for their blood glucose levels, and needed glucose infusion rates of greater than 8 mg/kg/min for several days to maintain normoglycemia. All infants recovered spontaneously. PMID- 1867878 TI - Neonatal effects of methyldopa therapy in pregnancy hypertension. AB - This study has been performed to assess the effect of methyldopa (MD) therapy in pregnancy hypertension on the neonatal adaptation. Infants born to mothers on MD for several weeks prior to delivery and presenting with excessive tremor and irritability were evaluated according to the dose of maternal MD. Pregnancy hypertension and high dose MD was associated with impaired placental perfusion, compromised function of fetoplacental unit and more frequent surgical delivery. Infants of mothers on high (1.25-2.0 g/day) or low (less than 1 g/day) MD had gestational age, head circumference, acid-base balance, Apgar score and blood pressure similar to those born to healthy control mothers. The birth weight of infants of the high MD group, however, were significantly lower than in the low dose or control groups. MD therapy resulted in a dose-dependent increase in plasma levels of prolactin, thyrotropin and triiodthyronine indicating decreased dopaminergic inhibition of pituitary hormone release. Plasma thyroxine concentration, however, decreased significantly. Cerebrospinal fluid noradrenaline was found to be markedly depressed after maternal MD showing disturbed central nervous system monoamine metabolism. It is suggested that MD administration to mothers presenting with pregnancy hypertension interferes with cerebral monoamine metabolism of the neonate and induces alterations in some endocrine functions under dopaminergic control. The possible role of chronic fetal distress frequently associated with pregnancy hypertension should also be considered. PMID- 1867879 TI - Euthyroid sick syndrome in type I diabetes mellitus in children and adolescents. AB - We studied concentrations of thyroid hormones (T3, T4, FT4, rT3, TBG and TSH) in 62 type I diabetic children and adolescents. The patients were classified into group A (n = 27, good control, HbA1c less than 10%), group B (n = 19, poor control, HbA1c greater than 10%) and group C (n = 16, diabetic ketoacidosis, pH less than 7.1 and HCO3 less than 15 mmol/L. All patients were treated with two daily injections of purified monocomponent insulins. Thirty healthy subjects of the same age served as control group. Patients in group B and C had significantly lower T3 and higher rT3 levels (p less than 0.001) compared to the matched controls (1.5 vs 2.2; 0.9 vs 2.2; 0.58 vs 0.3 and 0.6 vs 0.3 nmol/L). Serum TBG levels were significantly lower (p less than 0.01) in the group A (19.5 +/- 4.3 mg/L), group B (20.3 +/- 3.3) and group C (18.0 +/- 3.4) compared with control group (24.2 +/- 3.1). There was significantly negative correlation between T3 and HbA1c in group B (r = 0.546; p less than 0.02). The results of this study confirm that euthyroid sick syndrome does exist in type I diabetic children and adolescents with poor metabolic control and ketoacidosis. The inverse relationship between T3 and HbA1c percentage (low T3 and high HbA1c) points to the poor diabetic control. PMID- 1867880 TI - Postoperative echocardiographic study of patients following valvulotomy for critical valvular aortic stenosis. AB - Authors report on long term follow up of 12 patients operated with critical valvular aortic stenosis. They could perform control echocardiography in 11 patients 4-83 (mean 29) months after valvulotomy. The size and function of the left ventricle was found to be satisfactory, with elevated ejection fraction. The cause of the significant pressure gradient between the left ventricle and the aorta is discussed emphasizing the importance of echocardiography in determining the optimal time for valve replacement or homograft implantation. PMID- 1867881 TI - Value of brainstem acoustic evoked potentials in posterior fossa tumours in childhood. AB - Brainstem acoustic evoked potentials (BAEPs) were measured in 14 children with different type of posterior fossa tumours several times during the clinical course, in order to assess the value of this simple and non-invasive method in the diagnosis and follow-up of posterior fossa tumours in childhood. Eight children had midline medulloblastoma, three children had lateral astrocytoma, three had intrinsic brainstem glioma. Different BAEP patterns could be detected in different tumour's type: bilateral symmetrical or slightly asymmetrical I-V. IPL prolongation in midline medulloblastomas, unilateral or markedly asymmetrical I.-V. IPL prolongation or wave V. depression on the contralateral side in lateral astrocytomas, and severely distorted asymmetrical waveform in intrinsic brainstem gliomas. The BAEPs were abnormal earlier than CT scan in a case of craniospinal astrocytoma. BAEPs were useful in the follow-up: the effect of the preoperative chemotherapy or the progression of the inoperable tumours could be as well documented by this method, as by the CT scan. BAEPs proved effective in the assessment of postoperative neurological complications: bilateral symmetrical IPL prolongation and wave V. depression with clinical signs of increased intracranial pressure occurred in a case of postoperative occlusive hydrocephalus, unilateral IPL prolongation occurred during irradiation or chemotherapy after medulloblastoma removal as signs of cerebral oedema. PMID- 1867882 TI - [Pediatrics and pediatricians]. PMID- 1867883 TI - The care of infants and children. AB - The growth and development of pediatrics took place principally in the twentieth century. One result has been the reduction in deaths in the first year of life 165/1000 live births to 10/1000 live births in 1987. The birth rate was reduced by one-half during the same period. The challenges of the future are to consider the needs of American children in the context of the world's children, since isolation from global problems associated with logarithmic population growth in the developing countries and maldistribution of food is no longer possible. The time has come to consider the limits to application of our ever more sophisticated technology to support life at both ends of the spectrum of human life, the most immature and the most debilitated elderly. Human behavior continues to be unnecessarily destructive for children. Congenital AIDS and drug abusing parents are catastrophic for the infant. Accidents remain the leading cause of death of children in America. Deaths from diarrheal diseases and malnutrition are the main causes of death of children in developing countries. Nearly all of these problems are preventable with the application of current knowledge. How could we have let the best interests of children slip so far down on our national list of priorities in health care? PMID- 1867884 TI - Neonatal abdominal cystic masses: spontaneous regression demonstrated with ultrasound. AB - Abdominal cyst was diagnosed in 14 babies by ultrasound examination (9 multicystic dysplastic kidneys, 4 ovarian cysts, 1 bowel duplication). The cysts were followed in 6 patients by ultrasound and marked reduction of multicystic dysplastic kidneys was observed in 2 patients, and 1 ovarian cyst fully disappeared. Their experience in agreement with the literature data suggest that conservative management with sonographic reevaluation is an acceptable alternative to surgical therapy in uncomplicated cases. PMID- 1867885 TI - The diagnosis and treatment of the nonimmune hydrops fetalis. AB - Fetal hydrops is associated with two distinct pathophysiologic situations. The isoimmune hydrops fetalis is a well understood disorder, and as the result of medical advances and prophylactic therapy its frequency is diminishing. The nonimmune hydrops fetalis is a poorly understood disease with a bad prognosis. The two disorders can be differentiated with the indirect Coombs test. In both cases the ultrasound examination plays an important role in the diagnosis, prognosis and management. Examination of the fetal blood sample gives recently a possibility to approach the disease. In NIHF the examination of fetal blood sample would give a relatively quick and effective diagnosis but its value for the treatment is limited. Although with the present technology it is impossible to diagnose all cases of NIHF, the early recognizing, the careful and step by step investigation, the active perinatologic management mostly can show the etiology and can help the perinatal team at the treatment of the disease. PMID- 1867886 TI - Examination of the fetal heart with two-dimensional echocardiography. AB - The methodology of the two-dimensional fetal echocardiography is described by the basic of the accepted international nomenclature. By their opinion it is necessary that on the 18-20th weeks of gestation the high risk pregnants in aspect congenital heart disease examined by well-trained specialists. The indications of the echocardiography are listed, too. PMID- 1867887 TI - Urinary N-acetyl-beta-D-glucosaminidase activity in healthy, polycythemic and hypoxic neonates. AB - The authors investigated the urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in the case of 101 normal healthy and 20 polycythemic newborns and prematures, and 50 prematures suffering from hypoxia on the 1st, 2nd, 4th, 14th, and 28th day after birth. The obtained activities were referred to the creatinine concentrations of the urine samples and given as NAG index. There were no significant differences in the NAG indices either between fullterm and preterm babies or between appropriate for gestational age (AGA) and small for gestational age (SGA) neonates of the normal group. The NAG indices on the first day of life were significantly higher in the case of polycythemic newborn in comparison with the normal group (p less than 0.01). On the 14th day, after the partial plasma exchange, the NAG indices returned to the normal range. The premature babies suffering from IRDS received an average 10.1 days oxygen supplementation. Their NAG indices were significantly (p less than 0.01) higher on the 1st, 2nd, 4th days than those of the healthy prematures of the normal group and decreased considerably up to the 14th day. Finally the NAG indices reached the normal value on the 28th day. These results support the assumption that the urinary NAG index is a suitable indicator of the renal tubular damage during the newborn period. PMID- 1867888 TI - The effect of socio-economic conditions on the time of diagnosis and compliance during treatment in growth hormone deficiency. AB - In 78 patients with idiopathic growth hormone (GH) deficiency the effect of the fathers' educational level on the age and the extent of growth retardation at diagnosis was studied. There was a tendency for an increase of the age and the degree of growth retardation with the decrease of the fathers' completed grades. The occurrence of height SD scores less than -4.5 was conversely related to the number of grades completed by the father (chi 2 = 19.2 p less than 0.001). Eighteen of the 70 patients treated with growth hormone discontinued treatment after 0.3 to 6 years. Compliance was closely related to the grades completed by the father (chi 2 = 24.7 p less than 0.001). Six out of 7 patients with a height SDS less than -4.5 at diagnosis and with a father of low level of education (less than 8 grades) became non compliant. It is concluded that the degree of growth retardation at diagnosis and compliance at treatment in GH deficiency is related to the educational level of the father. PMID- 1867889 TI - Decreased sensitivity of cytostatic drugs in glucocorticoid receptor-free acute myeloid leukaemia cells. Clinical and experimental observations. AB - Preliminary clinical observations have suggested that low cellular glucocorticoid receptor (GR) levels might have been connected with multidrug resistance in children with acute myeloblastic leukaemia (AML). To test this possibility, we have developed glucocorticoid resistant subclones of two recently established human myeloid leukaemic cell lines. The cause of glucocorticoid resistance was GR negativity in these subclones. GR positive parent cell lines or GR negative subclones were incubated for 1 h in the presence of Adriamycin, Cytosine arabinosid, Etoposide or Vincristine, respectively. After short-term (1 h) incubation in suspension cultures cells were washed and plated in clonogenic agar cultures. Each anticancer drug was more potent against both GR positive parent cell lines than against the GR negative subclones. The results of this study suggest that the absence of GRs is a useful marker of multidrug resistance in childhood AML. PMID- 1867890 TI - Euthyroid sick syndrome in children with acute viral hepatitis A. AB - According to the clinical findings, the activity of serum asparate aminotransferase (EC 2.6.1.1), alanine aminotransferase (EC 2.6.1.2) and the level of total bilirubin, 45 children with acute viral hepatitis A were divided into two groups: with mild and moderately severe degree of disease. By determining the products of the peripheral thyroxine metabolism-T3 and rT3, as well as the other thyroid parameters (T4, FT4, TSH and TBG) we have found significantly lower T3 level and significantly higher T4 and TBG levels in both groups of patients in comparison with control group. At the same time, the level of biologically less active rT3 was increased in patients with moderately severe form of disease, while no differences were found in the values of TSH between the ill and control patients. TRH induced TSH release was normal in all patients. The results of this study point to the development of euthyroid sick syndrome or low T3 syndrome in children with viral hepatitis A. PMID- 1867891 TI - Pulmonary hydatidosis in childhood. Review of 21 cases. AB - Spain is one of the countries with a very high incidence of hydatidosis in the childhood. It represents 16.8% of all cases intervened for thoracic surgery for hydatidosis cysts in our department during the last ten years with a total of 21 children (inferior to 14 years) operated due to hydatidosis. Cough and pain were the symptoms more frequently encountered. The ratio unruptured/ruptured cysts was 3/1, higher than in the adults, with an average of 2.62 cysts per patient. Specific immunoglobulin E and histamine liberation test were the most useful tests in the laboratory. The usual surgical technique was a cystopericystectomy with total extirpation of the parasite of its rests. No recurrence was found in the follow-up of our patients. PMID- 1867892 TI - Carnitine content of red blood cells of human subjects treated with pivampicillin and carnitine. AB - Total- and free carnitine content of washed pooled red blood cells collected from five children prior to and on the last day of combined pivampicillin and equal molar carnitine treatment were measured. On the last day of treatment (day 7) the level of total carnitine decreased from 47.5 +/- 3.39 to 37.5 +/- 2.48 nmol/ml, mean +/- SEM (p less than 0.05) with a concomitant decrease of free carnitine (from 19.2 +/- 0.97 to 15.5 +/- 0.99 nmol/ml, p less than 0.05) as compared with the pretreatment control day (day 0). The calculated amount of acid soluble carnitine esters also fell (from 28.2 +/- 3.38 to 21.9 +/- 1.78 nmol/ml). The same effects were found when the carnitine levels were referred to haemoglobin or water content of samples. These results demonstrate that in pivampicillin treatment the carnitine pool of erythrocytes also alters. In agreement with previous findings the data presented here suggest, that the administered carnitine was not sufficient to meet the enhanced needs of the organism caused by the pivalate load and that the organism utilized some of its stores for pivaloylcarnitine production. The decreased carnitine ester level of erythrocytes suggest, that the red blood cells do not participate in significant extent in pivaloylcarnitine transport or production. PMID- 1867893 TI - Prenatal diagnosis of cystic fibrosis by microvillar membrane enzyme analysis in amniotic fluid. AB - Prenatal diagnosis was performed in 92 pregnancies high-risk for cystic fibrosis during six years. Amniotic fluid samples obtained by amniocentesis were examined with regard to their microvillar membrane enzyme activity. Though trehalase, alkaline phosphatase isoenzymes and L-gamma-glutamyltransferase in the amniotic fluid are not specific markers of cystic fibrosis, their activity is significantly lower than in normal pregnancies. By measuring the three enzymes simultaneously, sensitivity, specificity and reliability of the method were found to be over 92%. It is concluded that mid-trimester amniotic fluid diagnosis is indispensable for some heterozygotic couples for cystic fibrosis even in the possession of DNA (desoxyrobonucleic acid) methods. PMID- 1867894 TI - Improving physicians' and nurses' clinical breast examination: a randomized controlled trial. AB - Health professionals' clinical breast examination accuracy and skills are not optimal. We conducted a randomized trial to evaluate changes in physicians' and nurses' lump detection accuracy and examination skills after a training program emphasizing development of tactile skills and using silicone breast models containing lumps of varying sizes, degrees of hardness, and depth of placement. Sensitivity, specificity, and examination technique were measured before and four months after training in 43 experimental group and 46 control group participants. Mean sensitivity increased from 57% to 63% in the experimental group but decreased from 57% to 56% in the control group (P less than or equal to .05). The experimental group's posttest sensitivity was better for each lump characteristic, with statistically significant improvement for the very small (0.3 cm) and medium hard lumps. Duration of examination independently predicted sensitivity. Specificity decreased from 56% to 41% in the experimental group while it increased from 56% to 68% in the control group (P less than or equal to .05). Physicians had significantly higher mean sensitivity than nurses overall, as well as for the larger (1.0 cm), very small (0.3 cm), and softer lumps, but significantly lower mean specificity (33% versus 57%, P = .03). The experimental group improved significantly in five of six technique components while the control group improved in only one. To determine the effect of training on specificity in the clinical setting, we examined medical records of women seen by a subset of experimental and control physicians during the six months following training. There were no significant differences in the proportion of abnormal breast examinations reported or the number of mammograms ordered by experimental and control physicians. Our results show health professionals can be taught successfully to improve their clinical breast examination accuracy and skills. PMID- 1867895 TI - Psychosocial factors in the natural history of physical activity. AB - We studied the association between demographic, socioeconomic, and psychosocial factors and change in level of physical activity in 4,025 persons who were interviewed in 1965 and 1974 as part of the Alameda County study. Relative declines in physical activity were found to be associated with education level (less than a college education), race (being black or non-white [women]), low income, blue-collar occupation, unmarried status, group non-membership, social isolation, depression, personal uncertainty (women), low life satisfaction, and health perceived less than "excellent." These results demonstrate the multifactorial determination of level of physical activity. PMID- 1867896 TI - Survey of smoking patterns, attitudes, and interest in quitting. AB - We conducted a survey of 875 smokers in a Minnesota Heart Health Program community who were nonparticipants in screening and intervention. We found particular levels of interest in quitting and in formal cessation topics and programs among these smokers. Also, we collected information on smoking history, social environment, and anticipated barriers to quitting. Most noteworthy was the finding that more than half of the respondents indicated a desire to be contacted by telephone to receive information on materials on, classes on and ways of quitting smoking. Topics of particular interest to smokers included physical addiction, stress reduction, and (for women) methods of avoiding weight gain after quitting. Only 7% of respondents reported that they definitely did not want to quit, and approximately one-third of those interested in quitting indicated that they would seek outside help in doing so. The findings support the viability of "reverse" helpline procedures in which smokers are contacted directly and offered assistance in quitting. PMID- 1867897 TI - Patients' expectations of the family physician in health promotion. AB - This study evaluated patients' perceptions of the family practice physician's role in providing health promotion services. We distributed a questionnaire to a convenience sample of 450 patients (mean age = 40.4 years, SD = 15.8); 382 responded, yielding an 85% response rate. At least 70% of the respondents believed physicians should counsel all patients concerning yearly Pap smears, breast self-exams, and smoking cessation. A sizeable minority believed physicians should teach sex education to teens (41%), discuss social support systems with patients (41%), and discuss home-safety issues with patients (42%). The topics patients least wanted physicians to discuss were financial problems (32%) and seat-belt usage (31%). These patients thought physicians should refer them to other professionals for dental care (33%), marital problems (21%), and financial problems (20%). At least half of the respondents thought physicians should help in the following areas only if requested to do so by the patient: sexual problems (58%), sleeping difficulties (54%), and marital problems (53%). Chi-square analyses were conducted to examine differences in beliefs based on age, sex, educational level, and preventive health orientation of the respondent. We found significant differences based upon these demographic variables; however, interaction effects among the demographic variables also exist. PMID- 1867898 TI - Headache characteristics associated with physician consultation: a population based survey. AB - In a population-based telephone interview survey of 9,380 Washington County, Maryland, residents 12-29 years of age who reported a headache in the prior year, only 26.7% of women and 13.6% of men had ever sought a physician's advice for a headache problem. Women (13.9%) were more than twice as likely as men (5.6%) to have consulted a doctor for this condition within the previous 12 months. The likelihood of seeking medical care for headache increased with age among women but not men. Married women were more likely to have consulted with a physician for a headache problem than single or divorced women. Men and women consulting a doctor for this disorder within the previous 12 months described recent headaches (within the prior week) that were more severe, of longer duration (women only), and more likely to have migraine characteristics than recent headaches of persons not seeking medical attention. Compared with persons never consulting a physician for a headache problem, men and women who sought medical care had elevated attack rates of certain, probable, and possible migraine and mixed migraine-tension type headaches within the preceding week. Differences in attack rates for migraine and mixed migraine-tension headaches between those who recently and those who more than 12 months ago sought a physician's advice were more striking for men than for women. PMID- 1867900 TI - Review articles and disclosure of methods. PMID- 1867899 TI - Adolescent pregnancy in the United States: a review and recommendations for clinicians and research needs. AB - Adolescent pregnancy, often unplanned and unwanted, has a negative impact on the physical, emotional, educational, and economic condition of the pregnant teenager. Forty percent of the one million adolescents who became pregnant in 1986 chose abortion, and, of the remainder, 61% were unmarried. Teenage mothers in greater numbers and at younger ages are opting to keep and raise their children. In 1987 over $19 billion in federal monies were expended on families begun when the mother was a teenager. The preferred approach to this problem is prevention of teenage pregnancy rather than abortion, with emphasis on sex education and access to family planning information and contraceptive devices for both females and males. Sex education in schools is presented in widely varying formats; in fact, prevention of pregnancy may not even be presented. Family planning clinics are subject to the whims and biases of the funding agencies. Clinicians have an important role in providing guidance for teenage patients and their parents, but can also influence school and community leadership to ensure that all teenagers receive sound sex education in school programs and that family planning agencies are permitted to counsel teenagers and provide contraceptive devices. PMID- 1867901 TI - Is routine mammography screening appropriate for women 40-49 years of age? AB - This article reviews the evidence about screening for breast cancer. Results are now available from four randomized trials--one quasi-experimental study and three case control studies. Only the oldest, the Health Insurance Plan (HIP) Trial, shows any evidence of mortality reduction in women from 40 to 49 years of age. However, the evidence from the HIP trial is weak and somewhat contradictory. Preliminary data from a further trial in Sweden and the National Breast Screening Study in Canada confirm my conclusion that the scientific evidence is insufficient at present to recommend mammography screening for women 40-49 years of age. This conclusion reinforces the decision of the U.S. Preventive Services Task Force, but contradicts the guidelines of the American Cancer Society and the National Cancer Institute. PMID- 1867902 TI - Health and culture in rural Garhwal. PMID- 1867903 TI - The effects of co-worker-delivered prompts on breast self-examination frequency. AB - In this study, we evaluated the efficacy of co-worker-delivered reminders to perform breast self-examination (BSE). Before participating in a BSE training workshop, subjects (n = 36) were randomly assigned in pairs (of co-workers who registered together) to one of two experimental conditions: contract or control. Subjects in the contract condition, after discussing specific prompting strategies as part of a "buddy system" in their workshop, contracted to prompt their designated peers at least once a month for six months following the workshop. In addition, subjects in both conditions received mailed prompts monthly. We assessed BSE adherence and prompting behaviors in retrospective interviews. Results indicated that subjects in both conditions significantly increased BSE frequency above pre-workshop levels. However, the magnitude of this increase did not differ between conditions. A process evaluation indicated that the control group pairs were similar to the contract group pairs in their prompting behavior. PMID- 1867904 TI - [The use of computed tomography in assessing parotid masses]. AB - Thirty-one patients with suspected parotid masses have been studied by computed tomography (CT) without and with contrast to demonstrate the existence of this and to value possible relation between degrees of malignancy and the morphological characteristics of the masses. PMID- 1867905 TI - [The radiotherapy control of cervical adenopathies in undifferentiated epithelial tumors of the head and neck. The prognostic factors]. AB - A total of 90 patients with undifferentiated carcinomas tumors the head and neck with clinical neck nodes who received intended radical irradiation, were studied by means of a multivariant analysis of 9 variables which defined cervical lymph node disease in oder to determine the prognostic factors for the control of the above mentioned adenopathy. The factors were as follows: lymph node response post irradiation (p = 0.0000), condition of the primary (controlled-non controlled) (p = 0.0208). PMID- 1867906 TI - [A pharyngolaryngeal cancer study in the Autonomous Community of La Rioja]. AB - It has been studied the pharyngolaryngeal cancer in La Rioja region, Spain, about a population of 300,000. It has been commented on its frequency, distribution according to age-sex, alcohol-tobacco and evolution-recovery. PMID- 1867907 TI - [The prognostic value of conventional pathological anatomy in laryngeal epidermoid carcinoma]. AB - The anatomopathologic study of epidermoid carcinoma of the larynx is a reason for many publications in the international scientific community in spite of the apparent histologic similarity of this type of tumor. After a careful review from wide material the authors make reference to the prognostic value of certain anatomopathologic finding. PMID- 1867908 TI - [Monopolar endoscopic coagulation in posterior epistaxis]. AB - Most cases of severe nasal bleeding are treated by anterior and posterior packing of the nose. The permanence of the packing makes necessary an antibiotic therapy and sedation of restless patients. Extraction of the packs may lead to new bleedings from original vessel, but also from granulation tissue which may grow onto the nasal pack. The present paper offers an alternative treatment of severe nasal bleeding with the monopolar coagulation under endoscopic control, avoiding anterior and posterior nasal packing. PMID- 1867909 TI - [An immunohistochemical study of chronic otitis media]. AB - We use immunohistochemical procedures (OKT6) to detect LCs. We have studied tissue samples from surgical operations in cases of chronic otitis media. The samples were from skin of external ear canal, both the superior wall (close to cholesteatoma) and the inferior wall; we took also samples from the cholesteatoma matrix (epidermal and subepidermal stratum). We found LCs in the skin of external ear canal in similar proportion if the samples were of superior or inferior wall. In cholesteatoma tissue (17 cases) we observed LCs in the epidermal stratum in greater proportion than in skin. Sometimes the LCs form aggregates or "clusters". PMID- 1867910 TI - [The clinical evolution of transtympanic ventilation tubes in serous otitis. A study of 123 cases]. AB - A study was made to evaluate the results of 123 tubes in the treatment of patients with serous otitis media. The advantages of this procedure are exposed. PMID- 1867911 TI - [Olfactory esthesioneuroblastoma (we present 4 cases from our service)]. PMID- 1867912 TI - [2 cases of laryngeal amyloidosis]. AB - Two cases of amyloidosis involving larynx in a fifty-five-year-old male and a seventy-nine-year-old female have been presented. It is confirmed the most implication of the supraglottic area in the laryngeal amyloidosis. It has been discarded the general kind of the disease. The treatment by endoscopic remove was successful to improve the disease. PMID- 1867913 TI - [The preservation of hearing in surgery for acoustic neurinoma]. AB - The surgical result in one patient with unilateral tumor of the cerebellopontine angle and internal auditory canal is presented. Total tumor removal and preservation of hearing was possible in spite of the size of the tumor. The authors make some considerations about the possibility to preserve a useful hearing in patients with this type of tumors. PMID- 1867914 TI - [Olfactory neuroblastoma. A clinical and morphological study]. AB - A clinical and morphological study about neuroblastoma with olfactory differentiation are made. This study includes: TAC, vanimil mandelic acid urine determination, optic microscope, immunohistochemical technique, neuropeptidal, in situ hybridization, DNA analysis by flow cytometry and electronic microscope. PMID- 1867915 TI - [Acoustic emissions from the ear]. AB - In this paper we study the phenomenon of the acoustic emissions. This study presents two cases with different auditif pathology and their clinics applications. PMID- 1867916 TI - [Chemodectomas of the carotid body. Apropos 2 cases]. AB - The chemodectoma a paragangliomas of the carotid body are infrequent tumors in the daily medical practice, but they must be taken into account in the differential diagnosis of any lateral neck mass. We present two new cases, reconsidering the existing literature. PMID- 1867917 TI - [Effectiveness of maintenance treatment with cimetidine in duodenal ulcer. Variations depending on the risk group]. AB - One hundred and twenty-two patients with confirmed duodenal ulcer were treated with cimetidine during 6 or 12 weeks. After gastroscopic confirmation of healing, treatment was suppressed during 3 months. Patients were randomized into two therapeutic regimens: intermittent according to recurrence of symptoms and maintenance with 400 mg cimetidine. In patients considered as having mild disease (healing at 6 weeks without recurrence) fared better with maintenance therapy than with intermittent dosage. All patients with moderate to severe disease on intermittent therapy had a recurrence (criterion: more than 6 weeks for healing the ulcer or recurrence before three months). Those on maintenance therapy had the following results: no recurrences 28%, one recurrence 56% and more than one 16%. Ninety three patients were followed during one entire year. There was also a statistical difference in the number of severe complications among patients on continuous maintenance (nil) and those on intermittent therapy (8%, p less than 0.05). PMID- 1867918 TI - [Effect of alloxan-induced diabetes on hepatic regeneration]. AB - Hepatic regeneration in alloxan-induced diabetic rats that underwent a 70% hepatectomy was compared to that of a series of non-treated rats. In diabetic rats, hepatic regeneration is lower and the liver reaches only 70% of the original weight ten days after hepatectomy. Analytical studies in these rats show a diminution of insulin and glucagon. Hepatic microcirculation as shown by measurements of CLV-CLV and CLV area undergoes changes which evolve at a different rate in the central and peripheral zones of the liver. These findings as well as the diminished hepatic regeneration may be attributed to the diminution of the insulin and glucagon values. Insulin and glucagon may be responsible for hepatic regeneration. PMID- 1867919 TI - [Sixteen-year experience with gallbladder cancer. Review of 120 cases]. AB - We reviewed retrospectively 120 patients with histologically diagnosed gallbladder carcinoma and collected during 16-years (1974-1989). Age and sex, annual distribution, predisposing factors, histological findings, clinical manifestations, complementary diagnostic methods, therapeutic measures and follow up of patients were analyzed. Our results suggest the following conclusions: a) the annual incidence of gallbladder carcinoma remains unchanged; b) there is a close association with gallstones; c) the late diagnosis is due to unspecificity of clinical manifestations and low diagnostic effectivity of complementary methods; d) computed tomography and laparoscopy are the more effective complementary diagnostic methods in advanced gallbladder carcinoma; e) early gallbladder carcinoma is only diagnosed casually in cholecystectomy pieces; f) only the early carcinoma (grade I or II) is curable. PMID- 1867920 TI - [Evaluation of transparietal hepatic cholangiography in the diagnosis of cholestatic syndrome]. AB - Three hundred and thirty-two percutaneous cholangiograms were done in 313 patients. The etiology was benign in 137 cases and malignant in 152 instances. The level of obstruction was correctly localized in 97.8% of cases. The total sensitivity was 88.5% and specificity 95.9%. Positive predictive value 95.4% and negative predictive value 89.6%. Major complications occurred in 3.3% of cases. Complications occurred more frequently when the bile ducts were dilated. They were not related to the number of attempts to puncture ther biliary tree or the experience of the physician. PMID- 1867921 TI - [Prospective study of the prognostic value of C reactive protein, alpha 1 antitrypsin and alpha 1-acid glycoprotein in acute pancreatitis]. AB - Early recognition of severity of acute pancreatitis is very uncertain. For this reason it is necessary to have objective criteria to predict with accuracy the course of the disease. The aim of this study was to examine the value of the determination of the acute phase reactants: C reactive protein (CRP), alpha 1 antitrypsin (alpha-AT) and alpha 1-glycoprotein acid (alpha-GA) as prognostic indicators of acute pancreatitis on admission and on the third day. We have studied 40 patients with acute pancreatitis and serum concentrations of CRP, alpha-AT and alpha-GP were related to the Ranson Index. On admission the median levels of CRP: 74 mg/L, alpha-AT: 208 mg% and alpha-GA: 303 mg% were significantly higher (p less than 0.001) in patients with Ranson Index greater than or equal to 3 than in those with Ranson Index less than or equal to 2 (CRP: 166 mg/L, alpha-AT: 303 mg% and alpha-GA: 121 mg%). The values which differentiated patients with better and worse prognosis were: CRP 100 mg/L (sensitivity 100% and specificity 86%); alpha--AT 275 mg% (sensitivity 71% and specificity 85%); and alpha-GA 90 mg% (sensitivity 87.5% and specificity 57.9%). CRP, and to a lesser degree the alpha-AT and alpha-GA, were related to the duration of the ileus, and to the severe complications of the acute pancreatitis. PMID- 1867922 TI - [Peptic ulcer in the United States]. AB - The present paper reviews the epidemiology of peptic ulcer in the United States based on national statistics available through the National Center for Health Statistics and other federal or private institutions. About 5 million people currently have a peptic ulcer disease. More than 95 percent ever saw a physician for their disease, 65 percent visited their physician during the past year and 65 percent were currently under treatment for peptic ulcer disease. On the average, the ulcer led to 2.5 weeks of restricted activity per patient. About one week per patient was spent in bed due to the ulcer disease. The total number of physician visits for peptic ulcer ranged between 2 and 5 million per year. About 600,000 persons were discharged annually from hospitals with the diagnosis of peptic ulcer. In half of these discharges peptic ulcer was listed as primary diagnoses leading to 2.2 million hospital days or one week per case. Peptic ulcer was the primary cause of death in 6,700 subjects per year corresponding to a death rate of 28 per million living population. It was mentioned as secondary diagnosis on the death certificate of additional 11,000 people. Almost all US statistics revealed a marked decline in the occurrence of peptic ulcer during the past three decades. The decline affected all ulcer types, both sexes, and all races. It did not appear to be markedly influenced by any major medical improvements achieved in treating peptic ulcer disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867923 TI - [Gastroesophageal reflux and esophagitis (I). Physiopathology, diagnosis, surgical implications]. PMID- 1867924 TI - [Anisakiasis as a cause of acute appendicitis and rheumatologic picture: the first case in medical literature]. AB - We report a case of acute abdomen due to appendicular lumen occlusion by anisakis larvae. This is the first case of human anisakiasis known in Spain, and the first case of acute appendicitis, in the medical World literature, produced by this nemathode. The association of myalgias and arthralgias stands out, being in this aspect the second case found the in medical litterature. PMID- 1867925 TI - [Intestinal obstruction caused by foreign body in a patient with colon neoplasm]. AB - A case of intestinal obstruction due to ingested "foreign body" (a patient's tooth) is described in an elderly man with cancer of the ascending colon, at that time, without clinical symptoms. PMID- 1867926 TI - [Gastrointestinal involvement as the first manifestation of Schoenlein-Henoch purpura]. AB - A patient with Schonlein-Henoch purpura presented with gastrointestinal complaints as the first manifestation of the syndrome. The nature of the disease could be diagnosed after the late appearance of haematuria and purpura. PMID- 1867927 TI - [Primary segmental sclerosing cholangitis associated with Sjogren's syndrome]. AB - We report the case of a patient with primary sclerosing cholangitis associated with Sjogren's syndrome and Raynaud's phenomenon, an uncommon association. The presence of periportal lymph nodes with features similar to those described in autoimmune diseases suggests an immune pathogenesis of the disease. The localized and segmentary involvement of the common duct is also an uncommon finding. The pathogenetic and therapeutic aspects are discussed. PMID- 1867928 TI - [Gangrenous pyoderma associated with Crohn disease]. PMID- 1867929 TI - [A new case of aortoduodenal fistula diagnosis with endoscopy]. PMID- 1867930 TI - [Gastrojejunocolic fistula caused by recurrent ulcer]. PMID- 1867931 TI - [Perforated jejunal diverticulitis. Diagnosis with CAT]. PMID- 1867932 TI - Dental manpower in Florida continues to increase. PMID- 1867933 TI - Legible, concise and accurate records: a must! PMID- 1867934 TI - General rule may help to determine employee status. PMID- 1867936 TI - [Smoking]. PMID- 1867935 TI - [Tramping through a large women's organization. Interview by Bjorn Arild Ostby]. PMID- 1867937 TI - [NSF's professional groups: cooperative agreement next?]. PMID- 1867938 TI - [Smoke-free health facilities: nicotine slaves' "environmental TERROR" soon over?!?. Interview by Kjell Arne Bakke]. PMID- 1867939 TI - [Shall we refuse patients a smoke?]. PMID- 1867940 TI - [What do I get in retirement, tell me?]. PMID- 1867941 TI - Fatal pneumococcal septicaemia associated with asplenia and isomerism of the right atrial appendages. AB - A 22 month old male infant with isomerism of the right atrial appendages (associated with a complete atrioventricular septal defect, double outlet right ventricle, and pulmonary valve stenosis) died from pneumococcal septicaemia after a 36 hour illness. He had not been given penicillin prophylaxis. Asplenia was confirmed at necropsy. In a survey of 50 paediatric cardiologists in the United Kingdom, 13 (33%) of the 40 (80%) who replied did not advise any prophylactic measures against pneumococcal infection in patients with isomerism of the right atrial appendages. PMID- 1867942 TI - Familial aneurysms of the interventricular septum. AB - Congenital aneurysms of the interventricular septum were found in a 29 year old man and his four year old son. Both were symptom free. In both, M mode and cross sectional echocardiography showed an aneurysm in the mid-muscular trabecular portion of the ventricular septum with considerable paradoxical motion of the aneurysmal segment. Otherwise the chamber dimensions, intracardiac structures, and cardiac function were normal for age. Congenital aneurysm of the interventricular septum is rare and these familial cases may be unique. PMID- 1867943 TI - Successful operation on a coronary arteriovenous fistula in a 74 year old woman. AB - Coronary arteriovenous fistulas are rare and are usually diagnosed in children or young adults. Most are believed to be congenital. A right coronary arteriovenous fistula was first diagnosed in a patient of 74. Despite her age the fistula was successfully operated on and her symptoms were relieved. PMID- 1867944 TI - Early complications of interventional balloon catheterisation in infants and children. AB - Interventional balloon catheterisation is now the recommended procedure for several congenital heart defects. The overall complication rate in the first 160 children (median age 3 years) to undergo balloon intervention (excluding balloon atrial septostomy) at the Brompton Hospital was 24% (14% excluding haemorrhage and including three deaths (1.9%]. Most complications were related to vascular problems at the site of cardiac catheterisation. Complications were more common in the younger patient, especially neonates, and also in procedures that were ultimately unsuccessful. Most complications were transient and usually had no long term effects. Improvements in equipment design and technical expertise may reduce morbidity from these procedures. PMID- 1867945 TI - Balloon dilatation of tricuspid stenosis caused by carcinoid heart disease. PMID- 1867946 TI - Diagnosis of a pseudoaneurysm of the right ventricular outflow tract. PMID- 1867947 TI - Biomagnetometry: imaging the heart's magnetic field. PMID- 1867948 TI - Mechanism of shock associated with right ventricular infarction. AB - Various mechanisms have been proposed to explain the shock sometimes associated with right ventricular infarction, but only small numbers of patients with clinical shock have been studied. The haemodynamic profiles of seven patients with clinical cardiogenic shock after right ventricular myocardial infarction were studied prospectively. They were selected because all had a stable cardiac rhythm and none had absolute hypovolaemia during the study period. In all of them the mean right atrial pressure exceeded the pulmonary artery occlusion pressure. After treatment with varying combinations of dopamine, dobutamine, and glyceryl trinitrate (titrated to achieve the optimum haemodynamic response) the mean systemic arterial pressure increased, as did the cardiac index. There was an associated increase in the left ventricular stroke work index but the right ventricular stroke work index was unchanged. There was no significant change in heart rate, mean right atrial pressure, or pulmonary artery occlusion pressure. This suggests that the probable mechanism of the shock associated with right ventricular infarction is concomitant severe left ventricular dysfunction. PMID- 1867949 TI - Desirability of immediate surgical standby for coronary angioplasty. AB - OBJECTIVE: To assess the value of emergency surgical standby for percutaneous transluminal coronary angioplasty. DESIGN: Retrospective review of the major complications of coronary angioplasty in a regional cardiac centre. SETTING: All angioplasties were performed in the cardiac catheterisation laboratory of Wythenshawe Hospital with surgical standby in an adjoining operating theatre. PATIENTS: 1262 vessels were dilated in 1032 patients (mean age 53 years) between 1984 and 1989. MAIN OUTCOME MEASURES: In-hospital mortality from emergency surgical revascularisation after angioplasty; the rate of myocardial infarction and overall morbidity. RESULTS: Coronary angioplasty achieved primary success in 90% of cases. Thirty eight (3.7%) patients (five women (mean age 55.8) and 33 men (mean age 53.0] were referred for urgent surgical revascularisation--36 direct to operation and two within 24 hours. All patients survived surgery. Five of the 38 had had a previous angioplasty to the same vessel and one had had previous coronary artery grafts. Four of the 38 had an angioplasty for unstable angina. Eighteen had single, 13 double, and seven triple vessel coronary artery disease. The target vessel was the left anterior descending in 25, right coronary artery in nine, circumflex in three, and the left anterior descending and circumflex coronary arteries in one. Five required external cardiac massage on the way to the operating theatre; two of them had a left main stem occlusion. Four internal mammary artery and 60 reversed saphenous vein grafts were implanted (1.6 per patient). Complete revascularisation was achieved in 36 (94.7%) patients. Q wave myocardial infarction occurred in six (15.8%). The final outcome was: none dead, three patients with angina, one late death, one cerebrovascular accident, one late operation for a new left anterior descending lesion, two patients on diuretics with or without an angiotensin converting enzyme inhibitor. One orthotopic transplant was performed in a patient in whom cardiogenic shock developed after the left anterior descending coronary artery became occluded 72 hours after angioplasty. CONCLUSION: There was no surgical mortality and low morbidity among patients for whom immediate surgical cover was requested. PMID- 1867950 TI - Gradation of unstable angina based on a sensitive immunoassay for serum creatine kinase MB. AB - A newly developed, highly sensitive immunoassay for creatine kinase MB isoenzyme was evaluated in 68 patients with or without different types of ischaemic heart disease. Patients were classified on the basis of clinical criteria in four groups: no ischaemic heart disease, stable angina, unstable angina, and acute myocardial infarction. Enzyme concentration in patients with stable angina was the same (even during exercise) as seen in the patients without ischaemic heart disease. Patients with unstable angina, however, could be divided into two groups. One group showed clear evidence of severe myocardial ischaemia by serial changes and higher mean values of creatine kinase MB up to 40 hours after the onset of symptoms, whereas in the remainder values were stable and resembled those seen in the patients without ischaemic heart disease. The changes in concentration correlated with signs of repetitive ischaemic episodes deduced from continuous ST segment monitoring during the first 24 hours after admission. These findings indicate that patients with unstable angina are a heterogenous group. In some, severe and prolonged ischaemia can be detected by a serological assay with high sensitivity. PMID- 1867951 TI - Heart rate variability and cardiac autonomic function in men with chronic alcohol dependence. AB - Cardiac autonomic function was studied in 23 alcohol dependent men by standard tests of autonomic function and measurement of 24 hour heart rate variability. In all there was peripheral or central nervous system damage or both. Standard tests of autonomic function showed vagal neuropathy in seven. The remainder had normal autonomic function tests. Twenty four hour heart rate variability was measured as the standard deviation of the successive differences between RR intervals from an ambulatory electrocardiogram recording. Twenty four hour heart rate variability was significantly lower in both alcohol dependent groups than in controls, but the results in the two alcohol dependent groups were not significantly different from each other. The results of standard tests of autonomic function did not distinguish between the alcohol dependent men with normal autonomic function and controls. The differences in heart rate variability between this group and the controls may have been the result of the ability of this method to detect small changes in autonomic integrity. Cardiomyopathy may also account for some of these differences and such abnormalities should be excluded before results are to be regarded as a reflection of vagal function. Twenty four hour measurement of heart rate variability may be a more useful index of cardiac vagal neuropathy than currently available tests of autonomic function. PMID- 1867952 TI - Pulmonary microvascular permeability in patients with severe mitral stenosis. AB - Patients with rheumatic mitral stenosis often have no pulmonary oedema despite considerably increased pulmonary venous pressure. Pulmonary microvascular permeability was measured non-invasively by a previously validated method of double isotope scintigraphy with indium-113m and technetium-99m. This permits calculation of an index reflecting transferrin efflux and thus, indirectly, the microvascular permeability. Fifteen patients with severe mitral stenosis (defined as valve area less than 1.0 cm2) were compared with a control group of 11 patients with mild coronary artery disease. The permeability index was significantly lower in patients with mitral stenosis than in the control group. Furthermore, the extent of reduction of the permeability index correlated with the severity of mitral stenosis as reflected by the Gorlin valve area. This finding may account for the relative resistance of these patients to pulmonary oedema despite chronic pulmonary venous hypertension. PMID- 1867953 TI - Doppler ultrasound and the silent ductus arteriosus. AB - A clinically undetectable, small ductus arteriosus was identified by Doppler ultrasonography in 21 individuals. Infants were excluded from the study and no patient had pulmonary hypertension. Persistence of the ductus arteriosus is likely to be more common than shown by less sensitive diagnostic methods. Some patients considered to have infective endocarditis with a normal heart may have a silent ductus arteriosus. Evidence of such an association would justify ligation or antibiotic cover as prophylactic measures. PMID- 1867954 TI - Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. AB - A new tetrazolium analog of 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) was evaluated as a substitute for MTT in the microculture screening assay for in vitro cell growth. This new tetrazolium compound, 3-(4,5 dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H tetrazolium, inner salt (MTS), in the presence of phenazine methosulfate (PMS), gave a water-soluble formazan product that had an absorbance maximum at 490-500 nm in phosphate-buffered saline. The amount of colored product formed was proportional to the number of cells and the time of incubation of the cells with MTS/PMS. MTS/PMS was reactive in all the cell lines tested which included mouse leukemia L1210 cells, mouse Ehrlich tumor cells, mouse 3T3 fibroblasts, and human colon tumor cells (HT-29). HT-29 and 3T3 fibroblasts reduced MTS/PMS more efficiently than they reduced MTT. Comparable to the amount of product formed from MTT, MTS/PMS gave excellent product formation. The IC50 value for pyrazoloimidazole obtained using MTS/PMS was 200 microM; for 5-fluoro-2' deoxyuridine, the IC50 value was 0.9 nM. These values compared very favorably with the IC50 values obtained by direct cell counts. Further, the same IC50 values were obtained when the absorbances of the formazan product in the 96-well plates were determined after different times of incubation. PMID- 1867955 TI - Interaction between 5-fluorouracil, [6RS]leucovorin, and recombinant human interferon-alpha 2a in cultured colon adenocarcinoma cells. AB - Recombinant human interferon-alpha 2a (rIFN-alpha 2a; 500 or 5,000 IU/mL) or [6RS] leucovorin ([6RS]LV; 1 microM) each potentiated the cytotoxic activity of 5 fluorouracil (FUra) by 2.6- to 3.2-fold during 72 hr exposures in two human colon adenocarcinoma cell lines (GC3/c1; VRC5/c1). When all three agents were combined, FUra cytotoxicity was further potentiated by 3.2- to 4.3-fold (total 10- to 14 fold). Potentiation of FUra cytotoxicity occurred at clinically achieveable concentrations of rIFN-alpha 2a and [6RS]LV. Effects were reversed by dThd (20 microM), although the activity of CB3717, a quinazoline-based, specific inhibitor of thymidylate synthase, was not potentiated by rIFN-alpha 2a. Data suggest the requirement of a 5-fluoropyrimidine for biochemical modulation and interaction at the level of thymidylate synthase or DNA. PMID- 1867956 TI - Clinical pharmacology through the looking glass: reflections on the racemate vs enantiomer debate. PMID- 1867957 TI - Pharmacokinetics of codeine and its metabolites in Caucasian healthy volunteers: comparisons between extensive and poor hydroxylators of debrisoquine. AB - 1. The kinetics of codeine and seven of its metabolites codeine-6-glucuronide (C6G), norcodeine (NC), NC-glucuronide (NCG), morphine (M), M-3 (M3G) and 6 glucuronides (M6G), and normorphine (NM) were investigated after a single oral dose of 50 mg codeine phosphate in 14 healthy Caucasian subjects including eight extensive (EM) and six poor (PM) hydroxylators of debrisoquine. The plasma and urine concentrations of codeine and the metabolites were measured by h.p.l.c. 2. The mean area under the curve (AUC), half-life and total plasma clearance of codeine were 1020 +/- 340 nmol l-1 h, 2.58 +/- 0.57 h and 2.02 +/- 0.73 l h-1 kg 1, respectively. There were no significant differences between EM and PM in these aspects. 3. PM had significantly lower AUC of M3G, the active metabolites M6G, NM and M (P less than 0.0001), and lower partial metabolic clearance by O demethylation (P less than 0.0001). In contrast, the PM had higher AUC of NC (P less than 0.05) than the EM. There was no difference between PM and EM in the AUC of C6G and NCG, nor in the partial clearances by N-demethylation and glucuronidation. 4. Among EM, the AUC of C6G was 15 times higher than that of codeine, which in turn was 50 times higher than that of M. The AUCs of M6G and NM were about 6 and 10 times higher than that of M, respectively. The partial clearance by glucuronidation was about 8 and 12 times higher than those by N- and O-demethylations, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1867958 TI - A comparison of the pharmacokinetics of codeine and its metabolites in healthy Chinese and Caucasian extensive hydroxylators of debrisoquine. AB - 1. The kinetics of codeine and metabolites were studied in eight unrelated healthy Chinese subjects following a single oral dose of 50 mg codeine phosphate. The data were compared with those from eight Caucasian subjects who were matched with the Chinese group according to their metabolic ratio (MR) of debrisoquine. 2. Mean values of Cmax (445 nmol l-1) and AUC (1660 nmol l-1 h) of codeine in the Chinese were significantly higher than those in the Caucasians (292 nmol l-1 and 1010 nmol l-1 h). Thus plasma clearance was significantly lower (P less than 0.02) and the plasma half-life was longer (P less than 0.05) in the Chinese. 3. Partial clearance by glucuronidation was significantly lower (0.79 +/- 0.14 s.d. vs 1.42 +/- 0.48 s.d. 1 h-1 kg-1) in Chinese than in Caucasians. 4. The total urinary recovery of drug-related material in 48 h urine was similar in Chinese (82.2%) and Caucasians (84.4%). The recovery of unchanged codeine was significantly higher in Chinese (5.7%) than in Caucasians (3.3%). 5. The AUC ratios of codeine relative to its 6-glucuronide, morphine and norcodeine were 1:9, 35:1 and 4:1, respectively in Chinese. The corresponding ratios in Caucasians were 1:15, 50:1 and 6:1. 6. There was no significant difference between Chinese and Caucasians in the renal clearances of codeine and its primary metabolites. 7. Large interethnic differences in the kinetics of codeine have been shown. The Chinese are less able to metabolise codeine mainly because of a lower efficiency in glucuronidation. PMID- 1867959 TI - A screening test for slow metabolisers of tolbutamide. AB - 1. Six subjects participated in a detailed pharmacokinetic study of tolbutamide (pilot study). Using parameters based on these data, sixty-three non-diabetic volunteers underwent a simple screening test designed to identify slow metabolisers of tolbutamide. 2. The screening test was an estimate of tolbutamide plasma elimination half-life from plasma concentrations at 8 and 24 h after 500 mg tolbutamide orally, and urinary recovery of the hydroxy- and carboxytolbutamide metabolites over the 4-8 h post-dose period. 3. The mean tolbutamide half-life for 61 of the screened subjects was 7.5 +/- 1.5 h (range 5.2-12.2 h). Two subjects had half-lives of 21.6 and 16.1 h. Their urinary metabolite recoveries were within the range of those in the screening test but lower than those in the pilot study. 4. The subject with the 21.6 h half-life was restudied with intensive serial sampling for 72 h post-dose. She was confirmed as a 'slow' metaboliser of tolbutamide since her terminal half-life was 25.9 h but plasma Cmax and tmax were within the range of those in the detailed study. This subject's 24 h urinary recoveries of both hydroxytolbutamide and carboxytolbutamide were clearly different from the mean values for the pilot study subjects implicating hydroxylation of tolbutamide as the metabolic defect. 5. The two point plasma half-life is therefore a discriminatory screening test but a 4-8 h urinary recovery is not. 6. A partial family study did not provide conclusive evidence of the inheritance of slow tolbutamide metabolism but the screening test should allow simple identification of slow metabolisers for further study. PMID- 1867960 TI - Oxidation of reduced haloperidol to haloperidol: involvement of human P450IID6 (sparteine/debrisoquine monooxygenase). AB - 1. The conversion of haloperidol (HAL) to reduced haloperidol (RHAL) and then back to HAL has been established in vivo and observed in psychiatric patients. The reduction of HAL to RHAL is known to be catalysed by a ketone reductase, while the nature of oxidation back to HAL is the subject of the present study. 2. We examined the in vitro oxidation of RHAL to HAL in human livers. The activity was microsomal and evidence is presented to suggest that the sparteine/debrisoquine metabolizing isoenzyme P450IID6 contributes to this oxidation. 3. Reciprocal inhibition studies between RHAL and sparteine, a specific substrate for cytochrome P450IID6, indicated that both compounds compete for the same binding site. Quinidine, the most specific inhibitor for this cytochrome P450 potently inhibited the oxidative conversion of reduced haloperidol to haloperidol. A significant correlation (rs = 0.62, P less than 0.01) was found between RHAL oxidation and sparteine oxidation in a study involving 17 human liver samples. PMID- 1867961 TI - Faster and more reliable absorption of adrenaline by aerosol inhalation than by subcutaneous injection. AB - 1. The aim of the present study was to compare absorption of adrenaline given by aerosol spray inhalation with absorption after subcutaneous injection. 2. Arterial plasma adrenaline was measured in nine healthy volunteers following adrenaline administration by both methods. 3. Following inhalation of 20 puffs of adrenaline aerosol, 0.15 mg/puff, a peak arterial adrenaline concentration after 1 min and a rapid fall to baseline from this peak occurred. 4. When given by subcutaneous injection absorption was slower with a peak arterial adrenaline concentration after 4 min. The fall in arterial adrenaline from this peak level was not statistically significant within 30 min after injection. 5. There was less intersubject variation of arterial adrenaline concentration following inhalation when compared with injection. 6. Heart rate, blood pressure and finger tremor followed the changes in arterial adrenaline concentrations. 7. These results indicate that absorption is more reliable when adrenaline is given by inhalation. The rapid fall in arterial adrenaline following inhalation, suggests that repeated inhalations are necessary when such adrenaline therapy is required. PMID- 1867962 TI - The effect of cisapride on gastro-oesophageal dysfunction in systemic sclerosis: a controlled manometric study. AB - 1. Cisapride is a novel prokinetic drug which facilitates or restores motility throughout the gastrointestinal tract. Its mechanism of action is thought to involve enhancement of acetylcholine release in the myenteric plexus of the gut. 2. The effect of intravenous cisapride 10 mg on gastro-oesophageal dysfunction was investigated in 20 patients with systemic sclerosis, using a double-blind, randomised, cross-over, placebo-controlled manometric study design. 3. The increase in lower oesophageal sphincter pressure was significantly higher after cisapride (mean +/- s.e. mean, 8.3 +/- 2.1 cm H2O) than after placebo (mean +/- s.e. mean. 0.1 +/- 0.3 cm H2O) (P less than 0.001). The increase in the number of fundic gastric contractions during the 30 min study period was significantly higher after cisapride (mean +/- s.e. mean, 7.7 +/- 2.3) than after placebo (mean +/- s.e. mean, 0.9 +/- 0.6) (P less than 0.01). 4. No serious clinical adverse effects were observed. 5. The study demonstrates that intravenous cisapride induces a significant increase in lower oesophageal sphincter pressure and in the number of fundic gastric contractions, which may be beneficial in the treatment of scleroderma gastro-oesophageal dysfunction. Further long-term studies of the effect of oral cisapride in patients with systemic sclerosis are warranted. PMID- 1867963 TI - The activation of the biguanide antimalarial proguanil co-segregates with the mephenytoin oxidation polymorphism--a panel study. AB - The activation of the antimalarial drug proguanil (PG) to the active metabolite cycloguanil (CG) has been evaluated in a panel of 18 subjects. These subjects had previously been screened and classified as mephenytoin poor (PMm) or extensive metabolisers (EMm) and sparteine poor (PMs) or extensive metabolisers (EMs). Five subjects had the phenotype PMm/EMs, one was PMm/PMs, six subjects were EMm/PMs and six were EMm/EMs. The PG/CG ratio in urine (8 h) was significantly higher in PMm than in EMm (P = 0.0013). This study shows that the P450-isozyme involved in the polymorphic oxidation of mephenytoin is of critical importance in the activation of PG to CG and this may explain the large intersubject variability in CG concentrations in man. PMm make up about 3% of Caucasians, but up to about 20% of Orientals. From the present study, it may be anticipated that the antimalarial effect of PG is absent or impaired in this phenotype. The sparteine polymorphism appeared not to influence the activation of PG to CG significantly. PMID- 1867964 TI - Metabolism of verapamil in a family pedigree with deficient N-oxidation of trimethylamine. AB - The oxidative N-dealkylation of verapamil has been studied in a family of five members with two propositi with an inherited deficiency of trimethylamine N oxidation (fish-odour syndrome). The results were assessed for possible co segregation of the trimethylamine N-oxidation phenotype and any observed deficiency in oxidative N-dealkylation. The general pattern of metabolism of verapamil in the five subjects studied was similar to that reported in earlier investigations. Moreover, there were no differences between the two affected subjects and other family members with respect to the metabolic pattern. It is concluded that there is no functional segregation with respect to the mechanisms controlling trimethylamine N-oxidation and verapamil N-dealkylation. PMID- 1867965 TI - Stereoselective pharmacokinetics of disopyramide and interaction with cimetidine. AB - The pharmacokinetics of each of the enantiomers of disopyramide were examined after i.v. bolus administration of 150 mg racemic drug in a randomized cross-over study before and after the administration of cimetidine 400 mg twice daily orally. Clearance and volume of distribution (Vz) of total drug were significantly (P less than 0.001) higher for the R-(-) enantiomer than the S-(+) enantiomer (7.9 vs 4.6 l h-1 and 89 vs 50 l, respectively), whereas no significant difference in half-life could be demonstrated. The clearance of free drug was significantly (P less than 0.05) higher for the S-(+) enantiomer than that of the R-(-) enantiomer (34.6 +/- 5.4 l h-1 vs 27.2 +/- 5.6 l h-1), whereas no significant enantioselective difference in unbound volumes of distribution (258 +/- 38 l vs 226 +/- 42 l) could be demonstrated. Coadministration of cimetidine did not alter the pharmacokinetics of disopyramide. A significant concentration- or time-related decrease in the renal clearance of each of the enantiomers measured with respect to total drug in serum was observed, whereas renal clearances of the free enantiomers were similar. PMID- 1867966 TI - Pentoxifylline stimulates human sperm motility both in vitro and after oral therapy. AB - Pentoxifylline is a haemorrheologic agent often used in the treatment of peripheral vascular disorders. In this study, we measured sperm motility with a trans-membrane migration method and investigated the effect of this drug in the treatment of male infertility. We found that pentoxifylline increased motility of ejaculated spermatozoa in vitro from both normal and asthenozoospermic samples. After giving pentoxifylline to patients with asthenozoospermia for 3 months, sperm motility significantly increased, but sperm concentration did not increase. From the above results, it can be concluded that pentoxifylline is a useful drug in the treatment of normogonadotropic asthenozoospermia. PMID- 1867967 TI - Single dose pharmacokinetics and pharmacodynamics of oral oxazepam in very elderly institutionalised subjects. AB - The effect of extreme old age on the pharmacokinetics and pharmacodynamics of orally administered oxazepam 15 mg was studied in 10 healthy elderly (age 80-94 years) institutionalised subjects and 10 healthy young controls (age 26-42 years). The total oxazepam clearance was 1.24 (0.91-1.80) ml min-1 kg-1 (median and range) and 1.44 (0.88-2.13) ml min-1 kg-1 in the elderly and young, respectively (NS), and the elimination half-lives were 8.1 (5.5-10.8) h and 5.7 (4.9-6.2) h. respectively (P less than 0.01). The percent of unbound oxazepam was greater in the elderly; 9.8 (8.1-13.3)% as opposed to 5.1 (3.7-5.9)% in the young (P less than 0.0001). Clearance of unbound oxazepam was lower in the elderly, median values being 13.8 (7.1-21.1) ml min-1 kg-1 compared with 30.3 (18.3-41.5) ml min-1 kg-1 in the young (P less than 0.0001). A single 15 mg dose oxazepam decreased the ability of the elderly to perform a finger tapping test at 3 h but not 8 h after drug administration, whereas placebo had no effect at either times. No effect was observed in the young subjects. PMID- 1867968 TI - [Primary gastric lymphoma: our experience]. AB - The authors report their experience with 10 cases of primary gastric lymphoma observed in 10 years. Nonspecific symptomatology and bioptic features often misleading to benign lesions (pseudolymphoma) explain why an early diagnosis is difficult to achieve. A correct surgical treatment, with careful pre- and intraoperative staging, associated to pre- and postoperative chemo- and radiotherapy, allows good results in terms of survival. PMID- 1867969 TI - [Bronchopulmonary carcinoids: neoplasms with attenuated malignancy or true and proper malignant tumors?]. AB - The authors, in reporting their series of 6 bronchopulmonary carcinoids, dwell upon the criteria used to classify such neoplasms pointing out the related diagnostic problems. The presence of metastases and/or local recurrences as well as the impossibility to define the aggressiveness of the tumor brought the authors to consider such tumors as malignant. They conclude for a surgical approach which should be conservative: segmentectomy and lobectomy in elective procedures, whereas pneumonectomy and endoscopic resection should be reserved to particular cases. PMID- 1867970 TI - [Endometriosis of the distal ileal loop. A clinical case report]. AB - Intestinal endometriosis is a rare lesion characterized by a difficult differential diagnosis with other intestinal diseases. The authors report the case of a woman suffering from endometriosis involving the distal ileal loop. PMID- 1867971 TI - [The correlation of bacteriobilia/wound infections in elective biliary surgery]. AB - The authors report their experience concerning the cultural study of bile samples taken during elective biliary surgery. All the operations were carried out after a randomized preoperative antibiotic prophylaxis. Among the 138 cases examined the presence of surgical infections (wound infection) was taken into account. A lack of correlation between the germs present in the bile and those isolated from samples of complicated cases, was registered. However, the Authors emphasize that, although antibiotic prophylaxis gives a reduced percentage of postoperative infections, it is unable to sterilize the bile. PMID- 1867972 TI - [Hurthle's tumors of the thyroid: a clinical case and review of the literature]. AB - Hurthle tumors of the thyroid gland are uncommon lesions, histologically related to the well differentiated types of thyroid malignancies. Lesions predominantly composed of Hurthle cells are difficult for pathologists to be diagnosed and, consequently, for surgeons to be properly treated. In this report a case of Hurthle cell carcinoma was firstly treated with hemithyroidectomy plus isthmectomy; once frozen section examination revealed signs of malignancy a total thyroidectomy was performed. PMID- 1867973 TI - [Adenocarcinoma of the distal ileal loop: a rare disease at the typical site for Crohn's disease]. AB - The authors report their recent experience in the treatment of two patients respectively affected by Crohn's disease and adenocarcinoma of the terminal ileum. Although with some differences, they presented with radiological, pathological and gross morphological findings quite similar so that the authors concluded for a different clinical stage of Crohn's disease in both cases. Frozen section examination carried out in one of the two cases, established the correct diagnosis and indicated a wide resection instead of a very limited one. An extremely rare case of primitive adenocarcinoma of the terminal ileum is presented and the literature is reviewed. Features which could help the differential diagnosis between malignant lesions and regional enteritis are therefore focused. PMID- 1867974 TI - [An unusual case of spontaneous idiopathic hemothorax]. AB - Spontaneous haemothorax is an extremely rare pathology. Up to date, only 3 cases have been described in literature. The authors report the fourth case personally observed. PMID- 1867975 TI - [Primary volvulus of the omentum: a report of 4 cases]. AB - The authors report their experience in the diagnosis and treatment of primary torsion of the omentum. They emphasize the clinical findings of the cases observed for a better understanding of this uncommon abdominal pathology. PMID- 1867976 TI - [The radiotherapy of colorectal cancer]. PMID- 1867977 TI - [Free microvascularized flaps in head and neck lesions: the technics of microsurgical reconstruction]. AB - The authors report their experience of microsurgical reconstructive techniques using musculo-cutaneous free flaps after radical operations for head and neck neoplasms. PMID- 1867978 TI - Frequency of elevated urinary beta 2-microglobulin levels in relatives of patients with asymptomatic low-molecular-weight proteinuria. AB - We studied urinary beta 2-microglobulin levels in a total of 29 apparently healthy relatives (aged 0.8-70 years) of 8 male patients with asymptomatic low molecular-weight proteinuria in six families. The frequency of levels above the age- and sex-associated 95% confidence limit was 7 of 29 (24%), 4 of 12 (33%) in first-degree relatives, 2 of 6 (33%) fathers, and 2 of 6 (33%) mothers. These frequencies were significantly above those in the general population (P less than 0.01, by a normal distribution test, a binomial distribution, and Poisson distribution test for the sample proportion). The increased frequency in fathers argues against an X-linked pattern of inheritance for this entity, suggesting that there is heterogeneity in the inheritance. PMID- 1867979 TI - Urinary protein excretion and renal function in children with IgA nephropathy. AB - Renal haemodynamics and the pattern of urinary protein excretion were studied in 38 children (21 boys, 17 girls) with biopsy-proven IgA nephropathy (IgAN), 0.4 16.8 (median 5.3) years after onset of the disease. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were evaluated by clearances of inulin and para-aminohippuric acid. Serum and urinary albumin, IgG and beta 2 microglobulin (beta 2 mu) were determined and the excretion rates, clearances, and fractional clearances were calculated. The patients were grouped according to the type and the amount of proteinuria. Mean GFR and ERPF were significantly decreased (107 +/- 3 and 580 +/- 17 ml/min per 1.73 m2, respectively) versus controls (119 +/- 2 and 627 +/- 14 ml/min per 1.73 m2, respectively). Grouped according to albumin excretion rates, non-albuminuric patients had normal GFR, while mean GFR was reduced in patients with micro-albuminuria (106 +/- 3 ml/min per 1.73 m2) and albuminuric patients (92 +/- 7 ml/min per 1.73 m2). IgG excretion increased with increasing albuminuria, but the selectivity index was lower in albuminuric patients than in patients with micro-albuminuria. Albuminuric patients had also higher blood pressure than those with micro albuminuria. beta 2 mu excretion did not discriminate between patients with impaired renal function. The results suggest that childhood IgAN is not a benign kidney disease. After a median duration of 5 years of the disease a number of children had impaired renal function. Mean GFR was reduced most in the albuminuric patients but was also decreased in micro-albuminuric patients, indicating that micro-albuminuria may be a predictor of more severe disease. PMID- 1867980 TI - Should children with nephrotic syndrome be immunised against pneumococcal infection? PMID- 1867981 TI - Hemolytic uremic syndrome in children in northern India. AB - We observed 73 patients with the hemolytic uremic syndrome (HUS) in 9 years (1980 1988), comprising 34% of patients with acute renal failure treated over the same period. There were 53 boys and 20 girls; 59% were below the age of 2 years and 33% between 2 and 5 years. Acute, usually severe dysentery, responding poorly to various antibiotics, was the prodromal illness in 80%, whereas 12% had watery diarrhea. Most patients had severe renal involvement with anuria in 56% and oliguria in 30%. A polymorphonuclear leukocytosis was present in 85% of cases, but had no correlation with the highest levels of blood urea. Coagulation abnormalities suggesting consumption coagulopathy were found in 24 of 30 cases. The results of stool culture showed Shigella species in 7 cases and nontyphoidal Salmonella in 9. Escherichia coli were isolated in 11 cases, but were not further characterized. Renal biopsy showed total or patchy cortical necrosis in 20 of 50 cases. The patients were managed with supportive care, including transfusion of fresh blood or plasma and dialysis as required. The mortality was 60%, being chiefly related to the duration of renal failure and presence of renal cortical necrosis, whereas persistent dysentery and infections were complicating factors. The presence of convulsions and coagulation defects had no relation to the outcome. Our observations indicate that HUS in children in northern India is mostly related to dysentery, likely to be shigellosis, and is usually associated with severe renal damage and a high death rate. PMID- 1867982 TI - Antenatal sonography revealed bilateral moderate hydronephrosis without dilatation of ureters or bladder in a fetus at 16 weeks' gestation. This was confirmed at 32 weeks. What advice should be given to the obstetrician regarding intra-uterine intervention, delivery, etc? PMID- 1867983 TI - Haemolytic-uraemic syndrome associated with Aeromonas hydrophila enterocolitis. AB - Haemolytic-uraemic syndrome (HUS) associated with Aeromonas hydrophila enterocolitis is reported in a 23-month-old female infant. The A. hydrophila strain isolated from the patient's stool sample produced cytotoxin against verocells; increasing levels of cytotoxin-neutralizing antibody in the patient's sera were demonstrated, suggesting a recent infection. This report indicates that A. hydrophila should be suspected as a possible cause of HUS, and that this pathogen should be looked for in cases of post-diarrhoeal HUS. PMID- 1867984 TI - Steroid-dependent nephrotic syndrome following renal transplantation for congenital nephrotic syndrome. AB - A boy developed recurrent steroid-responsive nephrotic syndrome following renal transplantation for congenital nephrotic syndrome. The first episode was associated with mild tubulointerstitial rejection on kidney biopsy. Subsequent episodes showed normal histology by light microscopy and epithelial foot process fusion on electron microscopy, consistent with minimal change nephrotic syndrome. Serum analysis for soluble immune response suppressor was negative pre nephrectomy, positive during each bout of nephrotic syndrome, and negative during each remission. This case represents de novo occurrence of steroid-sensitive minimal change nephrotic syndrome following renal transplantation for congenital nephrotic syndrome. We stress the need for histological examination of the renal allograft to diagnose rejection, recurrent disease, or de novo disease. PMID- 1867985 TI - Renovascular hypertension: a rare cause of neonatal salt loss. AB - We report a case of severe hypertension in the newborn period due to obstruction of the right renal artery. The baby presented with polyuria leading to dehydration and was found to have hyponatraemia and severe renal salt loss. When sudden malignant hypertension is induced in experimental conditions, a high pressure diuresis and increased angiotensin II production are found. These findings could explain the renal salt loss, notwithstanding the effects of secondary hyperaldosteronism and hyper-reninaemia. PMID- 1867986 TI - The effects of vitamin E on tissue oxidation in nephrotoxic (anti-glomerular basement membrane) nephritis. AB - The effects of vitamin E on tissue oxidation, kidney function and morphology were studied in rats with nephrotoxic nephritis (NTN). Thirty-six nephritic animals received no treatment (group 1), while 36 were treated with vitamin E (group 2). Twenty-four hours after the administration of anti-glomerular basement membrane antibody, sulfhydryl-containing renal protein was significantly lower in group 1 than in group 2 (0.70 +/- 0.16 and 1.08 +/- 0.06 mmol/100 g kidney tissue, respectively), suggesting a free oxygen radical scavenging effect of vitamin E in group 2. The difference was similar on day 14. The creatinine clearance was significantly lower in group 1 than in group 2 on day 1 (40 +/- 30 and 204 +/- 60 microliter/min per 100 g body weight, respectively). The protein excretion was initially high in both groups, but a significant decrease was detected in group 2 relative to group 1 on day 14 (25 +/- 18 and 92 +/- 38 mg/24 h, respectively). The morphological changes were less severe in group 2. Vitamin E treatment did not alter any of the above values significantly in healthy animals. The release of oxygen free radicals in NTN might play an important role in the pathogenesis, which can be influenced by free radical scavengers through changes in kidney function and morphology. PMID- 1867987 TI - Growth, free plasma and muscle amino-acids in uraemic rats fed various low protein diets. AB - The nutritional effects of low-protein diets are difficult to assess in humans. Normal and uraemic growing rats were therefore fed: a moderately low-protein (12%) reference diet (diet R), two 5% casein diets, one supplemented with essential amino acids (AA) (diet A) and the other with their keto acids (diet K), and a 7% casein diet isonitrogenous with diet K (diet L). Appetite and growth of both uraemic and control rats were identical on diets R and A and were reduced on diets K and L. Stunting was prominent in rats fed diet L and more severe than in those on diet K. Diet K induced marked anorexia in controls. This effect was smaller in uraemic rats, which were all anorectic, regardless of the diet. Plasma essential AA were similar in rats on diets R and A but low in control rats fed diets L and K. In particular, diet K did not improve the branched-chain AA levels although it produced better growth than diet L. Plasma and muscle threonine were surprisingly elevated in rats on the semi-synthetic diets A and K, despite identical or lower consumptions. Regardless of the diet, uraemia resulted in unchanged or increased plasma essential AA, despite reduced appetite and stunting. Uraemia caused a marked rise in some non-essential AA. Muscle essential AA, except for threonine, were essentially unaltered and did not correlate with growth or uraemia. PMID- 1867988 TI - Progressive renal insufficiency in methylmalonic acidemia. AB - Methylmalonic acidemia is a heterogeneous inborn error of propionate metabolism. Therapy frequently includes a low-protein diet to minimize precursors of methylmalonic acid (MMA) and reduce its concentration in body tissues. Renal dysfunction in these patients is increasingly recognized. Tubulointerstitial disease has been found in the small number of renal biopsy specimens from young children previously reported by others. We describe an 18-year-old patient with the mut- form of the disease who developed renal dysfunction despite the use of a low-protein diet. Tubulointerstitial injury was documented by renal biopsy. The patient had no risk factors associated with established causes of chronic tubulointerstitial nephropathy (CTIN). We postulate that methylmalonyl-CoA and/or its precursors (propionyl-CoA, odd-chain fatty acids), may be capable of producing CTIN. We speculate that prevention of renal injury may require lower tissue levels of MMA and its precursors than those required for prevention of ketoacidosis. PMID- 1867989 TI - Combined liver-kidney transplantation in a child with primary hyperoxaluria. AB - A 3.5-year-old boy presented with end-stage renal disease and bilateral nephrocalcinosis. Renal biopsy demonstrated marked parenchymal calcium oxalate deposition and a diagnosis of primary hyperoxaluria (PH) was made. Following 2 years of hemodialysis he received two renal allografts which were lost at 7 and 11 months, respectively, due to biopsy-proven recurrent oxalosis. Combined liver kidney transplantation was then performed, after which renal and hepatic function initially stabilized. The patient died on the 28th postoperative day, of infectious complications and progressive respiratory insufficiency. However, comparisons between the patterns of urinary oxalate excretion noted after the isolated renal and liver-kidney transplants indicated that, following the latter, successful biochemical correction of the enzyme defect responsible for type 1 PH had occurred. PMID- 1867990 TI - Prostaglandin inhibitors in the treatment of nephrotic syndrome. AB - The management of nephrotic syndrome resistant to corticosteroid and cytotoxic therapy is unclear. In such patients, prostaglandin inhibitors can reduce proteinuria. Mechanisms may include a reduction in transcapillary hydraulic pressure and a decrease in capillary wall permeability. The antiproteinuric effect of these agents is enhanced by volume depletion induced by sodium restriction and thiazide diuretics. Complications may include aggravation of edema, hemodynamic renal failure, hyperkalemia, and drug nephrotoxicity. Although a reduction in protein excretion may improve the clinical status of nephrotic patients, it is unclear whether such methods will improve renal survival. PMID- 1867991 TI - Surgical aspects of urolithiasis in children. AB - Operative management of renal calculi has changed radically in the last decade. New operative techniques, the use of intra-operative ultrasound and Doppler sonography have even made possible the removal of complete staghorn calculi in short and kidney-preserving procedures. The introduction of percutaneous nephrolithotomy and stone extraction using a specially designed ureteroscope and, above all, the clinical application of extracorporeal shock wave lithotripsy have made stone surgery less invasive and have provided a higher rate of preservation of kidney function. PMID- 1867992 TI - Trials and tribulations of multicenter studies. Lessons learned from the experiences of the Southwest Pediatric Nephrology Study Group (SPNSG). AB - Multicenter studies in Pediatric Nephrology have been acknowledged in recent years as an important mechanism for studying renal disease in children. The purpose of this review is to describe some of the experiences of the Southwest Pediatric Nephrology Study Group (SPNSG) in order to assist others in developing their own multicenter studies. The importance of protocol development, including adequate attention to study design, data management, and data analysis, is emphasized. Mechanisms for facilitating the frequency and productivity of study group meetings that are so essential for the success of multicenter studies, are described in some detail. The need and some of the methods for achieving ongoing collaboration within a climate of critical peer review are also discussed. Controversial issues such as authorship and the question of institutional credit for involvement in multicenter studies are discussed in brief. Finally, some of the features of the SPNSG that have permitted us to maintain a relatively high rate of productivity are described. The two most important of these, ongoing commitment to the group and willingness to collaborate across differences of opinion, are stressed throughout the review. PMID- 1867993 TI - Immunological mediators and glomerular cell function. PMID- 1867994 TI - The role of the pediatric nephrologist in the care of children with diabetes mellitus. AB - The pediatric nephrologist has traditionally not been involved in the care of the diabetic child since diabetic nephropathy presents in adulthood. Recent studies suggest that diabetic kidney disease develops silently during childhood. Measurement of urinary albumin excretion (UAE) allows earlier detection of patients at risk of nephropathy, often in adolescence. In addition to diabetic nephropathy, diabetic children are at risk of urinary tract infections, renal papillary necrosis, and various forms of glomerulonephritis. The role of the pediatric nephrologist in the care of the child with diabetes might include advising on the administration and interpretation of screening for UAE and the measurement and interpretation of glomerular filtration rate, and blood pressure. Children with evidence of renal dysfunction should be evaluated and treated by the pediatric nephrologist. Frequently, renal biopsy will be necessary in these patients. Future research may allow the detection of diabetic kidney disease earlier in childhood, further expanding the role of the pediatric nephrologist. In particular, early renal biopsy may eventually be used to select those patients at risk of diabetic nephropathy for specific treatment alterations. PMID- 1867995 TI - Clinical quiz. Primary hyperoxaluria (PH) type 1. PMID- 1867996 TI - Left renal vein entrapment. PMID- 1867997 TI - Congenital urinary anomalies associated with neural tube defects. PMID- 1867998 TI - Embryonic sex hormones in birds. AB - Hormone activity of embryonic gonads in birds was demonstrated by grafting and culture experiments. Anti-Mullerian hormone responsible for the regression of the Mullerian ducts in the male is most probably a glycoprotein. Whether the testis also secretes testosterone has long been disputed, but most arguments are against this possibility. From early stages of development, the ovary secretes estrome and estradiol. However, it could not be demonstrated unambiguously whether estrogen is identical with the sex inducing substance in the female. The hypophysis seems to control ovarian estrogen secretion at 10-13 days of incubation in the chick embryo. PMID- 1867999 TI - Histone H1c decreases markedly in postreplicative stages of chicken spermatogenesis. AB - The relative proportions of four major chicken histone H1 subtypes (referred to as H1a, H1b, H1c and H1d) change markedly in different chicken tissues. The relative amount of H1c is higher in nonreplicating somatic tissues, such as liver, than in replicating immature testis. The proportion of H1c sharply decreases as spermatogenesis proceeds, being much lower in mature than in immature testis. It has been proposed that the relative increment of H1c correlates with low rates of cell division in chicken tissues. It was assumed that the sharp decrease in H1c observed during maturation of chicken testis was a consequence of the intensification of proliferative activity in spermatogonia (Berdnikov et al., 1976). Our results, however, clearly show that the decrease of H1c during maturation is due to the low levels of this protein in postreplicative stages of spermatogenesis, where H1c is barely detectable. These results suggest that the presence of the arginine-rich H1c subtype would neither be compatible with the relaxed structure of acetylated chromatin present in active replicating cells nor with the hyperacetylated chromatin characteristic of postreplicative late spermatids undergoing the nucleohistone nucleoprotamine transition. PMID- 1868000 TI - The pachytene chromomere map of the oocyte of the Turkish hamster (Mesocricetus brandti). AB - A study of the chromomere maps of the sex and twenty autosomal bivalents of Turkish hamster pachytene oocytes was carried out. The average total number of chromomeres in early/mid pachytene autosomes was 280 with 91 on the p (short arm) and 189 on the q (long arm). The submetacentric X1 chromosome had 20 chromomeres and the metacentric X2 had 27. Comparisons of the number and location of oocyte chromomeres are made with the pachytene spermatocyte chromomere maps of this species. PMID- 1868001 TI - Evaluation of anionic histological dyes as co-injectable cell markers in pre implantation mouse embryos. AB - The enzyme horseradish peroxidase (HRP) is a widely used microinjectable cell marker for studying cell position, lineage, and migration in many kinds of animal embryos. Marked cells are easily identified because they darken when exposed to a chromophore and an HRP substrate such as hydrogen peroxide. This assay, however, requires cytochemical fixation. Thus, when HRP-marked cells need to be identified prior to fixation, visible co-injectants such as dyes and fluorescent substances have been used with HRP. Fluorescent substances have limitations because their excitation could be harmful to the marked cells. Visible but non-fluorescent co injectants, however, would permit visualization of HRP-marked cells without inflicting such damage. We tested the compatibility of several histological dyes and electrolytic carriers with HRP iontophoresed as a cell marker in 2-cell mouse embryos. The dyes tested were Evans Blue, Cibacron Blue F3GA, Fast Green FCF, and Patent Blue Violet; the electrolytic carriers were KCl, K2SO4, CH3CO2K, and KH2PO4. The combination found most useful was Patent Blue Violet in K2SO4. Survival of embryos incubated to the blastocyst stage following injection with HRP + Patent Blue Violet in K2SO4 at the 2-cell stage was significantly greater than that of embryos injected with any other dye. Although the proportion of embryos undergoing the 8-cell-to-morula transition was somewhat decreased by this treatment, the proportion of embryos reaching the blastocyst stage was comparable to that in the uninjected (control) group. Our results indicate that Patent Blue Violet is a useful, HRP-co-injectable dye for short-term cell marking in preimplantation mouse embryos. PMID- 1868002 TI - The role of the polarizing zone in the pattern of experimental chondrogenesis in the chick embryo interdigital space. AB - We have previously shown that removal of the apical ectodermal ridge of the third interdigital space of the chick leg bud at stages 28 and 29 is followed by the appearance of ectopic cartilage, which in the course of development gives rise to extra digits. These in vivo studies suggest that the pattern of skeletal morphogenesis in the limb depends on the inhibitory effect of the ectoderm. In the present study we tested whether zone polarizing activity (ZPA) exerted an effect on the pattern of experimental chondrogenesis in the interdigital space of the leg bud in stage 29 HH chick embryos. A small fragment of tissue from the ZPA in chick embryos in which ZPA activity was most intense was grafted onto the interdigital space in which chondrogenesis had previously been experimentally induced. No significant changes were observed in the course of differentiation of the recipient interdigital spaces with ZPA grafts, leading us to conclude that the graft failed to modify the morphogenetic fate of interdigital tissue. PMID- 1868003 TI - The hatching mechanism in Atlantic halibut (Hippoglossus hippoglossus). AB - In general fish larvae emerge from the protective egg after secreting a hatching enzyme (HE) from diffusely located hatching gland cells (HGCs). This proteolytic enzyme is distributed over the entire inner part of the eggshell (zona radiata). In a marine flatfish halibut, (Hippoglossus hippoglossus), we have found a more specialized hatching process. A strategic location of the HGCs in a narrow belt on the anterior part of the yolk sac leads to restricted degradation of the eggshell resulting in cleavage of the eggshell into two distinct rigid parts. This hatching process--termed "rim-hatching"--results in an empty eggshell with a lid approximately 1/4 the size of the bottom shell. During the hatching process the yolk sac is reshaped. The posterior part of the yolk sac contracts and the yolk mass is squeezed forward before hatching. This mechanism ensures close contact between the HGCs and the eggshell during the release of the hatching enzyme, which is a prerequisite for restricted degradation of the eggshell. PMID- 1868004 TI - New developments in diagnosing HIV infections. PMID- 1868005 TI - Tuberculosis and HIV disease. PMID- 1868006 TI - Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Pathophysiology and therapy. PMID- 1868007 TI - Biologic features of HIV-2. An update. PMID- 1868008 TI - AIDS-associated lymphomas. PMID- 1868009 TI - Risk of HIV infection in health care workers. PMID- 1868010 TI - The clinical significance of HTLV-I and HTLV-II infection in the AIDS epidemic. AB - Although early reports of an etiological role of HTLV-I in AIDS are not supported by subsequent epidemiologic and biologic data, all AIDS specialists should be aware of the possible infection of AIDS risk group members with the HTLV viruses. In the United States, HTLV-II and HIV co-exist in high prevalence among IVDU, and coinfected IVDU may progress more quickly to AIDS. The health effects of solitary HTLV-II infection are currently unknown. In Africa and the Caribbean, where HTLV I is endemic, the epidemic of HIV infection will likewise produce coinfection and possibly faster progression to AIDS. In addition, adult T-cell leukemia/lymphoma and HTLV-associated myelopathy (HAM/TSP) may occur in persons infected with HTLV I alone. Clinical care of HTLV infected patients is difficult because of societal confusion of these viruses with HIV. The full health effects of both HTLV-I and HTLV-II are not yet known, and even the two known disease outcomes of HTLV-I infection occur in only a few percent of those infected. Without prognostic indicators, and with the long latency from infection to disease, counseling and medical follow-up of patients is difficult. Further research into the clinical effects of HTLV-I and HTLV-II is urgently needed. PMID- 1868011 TI - Bacteremia in persons with HIV infection. PMID- 1868012 TI - Bacillary angiomatosis. PMID- 1868013 TI - Controversies regarding the natural history and treatment of syphilis in HIV disease. AB - Because of the immunologic dysfunction of HIV-infected patients, concomitant infection with T. pallidum requires that maximal doses of appropriate antibiotics be given, and the expected falls in nontreponemal antibody titer cannot be relied upon to certify a cure. Genital ulcer disease appears to increase the risk of acquiring HIV. Therefore, all HIV-infected persons and persons with syphilis should be tested for both syphilis and HIV. PMID- 1868014 TI - The amsacrine story: will it change the FDA policy? PMID- 1868015 TI - Perhaps not everyone knows that ... PMID- 1868016 TI - Timing of breast cancer surgery in the menstrual cycle and outcome. PMID- 1868017 TI - Speech is silver, silence is gold? PMID- 1868018 TI - Prognostic factors analysis in clinical oncology: handle with care. PMID- 1868019 TI - HIV-associated non-Hodgkin's lymphomas. PMID- 1868020 TI - Hematopoietins: biology, pathophysiology, and potential as therapeutic agents. PMID- 1868021 TI - Outdoor air pollution and lung cancer. PMID- 1868022 TI - Timing of breast cancer surgery within the menstrual cycle: influence on lymph node involvement, receptor status, postoperative metastatic spread and local recurrence. AB - Prompted by a report of Hrushesky et al. stating that women operated upon for breast cancer during their perimenstrual period showed a higher risk for developing future metastases than women operated upon during their mid-cycle, we examined the patients with breast carcinoma who were treated at the Gynaecological University Hospital Zurich between 1971 and 1988 with respect to the influence of menstrual cycle phase on certain factors. 104 patients underwent perimenstrual surgery, i.e., between days 1 and 6 or days 21 and 36 of the cycle. 120 women had mid-cycle surgery (i.e., days 7-20 of the cycle). In contrast to the experience of Hrushesky et al., we found no significant differences in the survival curves. The same was true when the proliferative phase (days 1-14; n = 109) was compared with the secretory phase (days 15-32; n = 108). We tested the different groups for homogeneity and found that 54% of the patients with perimenstrual surgery showed axillary lymph node involvement, whereas in the midcyclic group only 38% showed positive nodes. We have no plausible explanation for this difference. These findings indicate that there might be certain cycle related differences with respect to lymph node status but that they do not affect survival. Hence, timing surgery to the menstrual cycle is not mandatory for the time being. PMID- 1868023 TI - Disclosure of breast cancer diagnosis: patient and physician reports. GIVIO (Interdisciplinary Group for Cancer Care Evaluation, Italy) AB - Although there is considerable controversy about what information regarding the diagnosis of cancer is most helpful to patients in meeting their psychological and medical needs, little research exists on what patients who are treated in non specialized institutions are told about their diagnosis and treatment. We assessed the information that breast cancer patients received about their diagnosis from the perspective of both the patient and the physician, in order to determine whether they agree in their perceptions of communication, and whether the nature of patient-physician communication is associated with patient satisfaction. Questionnaires were completed by 1171 Italian breast cancer patients (representing a 81.5% response rate) and their physicians at the time of surgery for breast cancer. Only a minority of patients (47%) reported having been told that they had cancer. Satisfaction with information was highest among women who had been told the diagnosis. Patient and physician reports of what information was conveyed about the diagnosis differed for over half of patients, with highest satisfaction levels reported when both patient and physician stated that the diagnosis had been conveyed. While comparison of patient and physician reports should not be used to validate either source of information, the degree of patient-physician disagreement found in this research may alert physicians to potential difficulties that can arise in communicating with cancer patients. PMID- 1868024 TI - Prognostic factors for overall survival in patients with advanced ovarian carcinoma. AB - Twenty-one pretreatment variables were investigated for prognostic influence on survival in 301 previously untreated patients with ovarian carcinoma, stage IIB IV. Patients were randomized to sequential combination chemotherapy: cyclophosphamide, doxorubicin, 5-fluorouracil, followed by cisplatin and hexamethylmelamine, or to the 3-drug combination alternating with the 2-drug combination every other month. Median overall survivals were 25 and 22 months, respectively, P greater than 0.4. Based on the results from a Cox multivariate stepwise analysis a subset of independent significant prognostic factors was found to include: residual tumor size, performance status, alkaline phosphatase, number of metastases, histological differentiation grade and type. A prognostic index was calculated for each patient and three prognostic categories of patients were determined. The 3-yr survival rates for patients with low-, intermediate-, and high-risk scores were 62, 31, and 7%, respectively. Multivariate analysis thus contributes further information about the disease, and a knowledge of the distribution of such factors across different trials is important when comparing treatment outcome. PMID- 1868025 TI - HIV-associated non-Hodgkin's lymphomas: clinical characteristics and outcome. The experience of the French Registry of HIV-associated tumors. AB - From 1/87 to 12/89, the French Registry of HIV-associated tumors recorded 131 cases of intermediate- and high-grade non-Hodgkin's lymphomas (NHL). There were 47 small non-cleaved Burkitt-type lymphomas (SNCL), 32 immunoblastic lymphomas (IL) and 52 diffuse large-cell or predominantly large-cell lymphomas (LCL). There were differences in the clinical patterns of the histological subtypes. Isolated extranodal presentation was less frequent in SNCL (2/47) than in IL (13/32) and LCL (17/49) (p less than 0.0001). In the latter two groups, the central nervous system was the principal site of extranodal involvement (16/30), 87% of SNCL, patients had no previous manifestations of AIDS whereas 40% of IL and LCL patients presented full-blown AIDS (p less than 0.01). At the time of NHL diagnosis, the median blood CD4 lymphocyte count was higher in SNCL (266/microL) than in LCL (125/microL, p less than 0.05) and IL (80/microL, p less than 0.01), 69% of stages I/II patients, 31% of stages III/IV, and 33% of stage ie patients achieved complete remission (CR), p less than 0.05. Overall median survival time was 5 months. There was no statistical difference in CR and survival rates among histological types. The two-year actuarial survival rate was 25% (median 8 months) for initially asymptomatic patients or those with persistent generalized lymphadenopathy (PGL) and 9% (median 3 months) for those previously with AIDS related complex (ARC) and AIDS patients (p less than 0.001). Response to treatment was the other predictor factor. The two-year survival rate was 42% (median 16 months) for patients who achieved CR, and 5% (median 3 months) for those who did not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868026 TI - Phase II study of combining vinblastine and cyclosporin-A to circumvent multidrug resistance in renal cell cancer. PMID- 1868027 TI - High-dose DTIC in advanced soft-tissue sarcomas in the adult. A phase II study of the E.O.R.T.C. Soft Tissue and Bone Sarcoma Group. AB - Forty-four of 50 adult patients with advanced soft-tissue sarcoma who had received previous chemotherapy were evaluable for response after treatment with DTIC. The therapeutic schedule consisted of DTIC 1.2 g/m2 infused over 20 minutes, and repeated every 3 weeks. There were 1 complete and 7 partial remissions (objective activity 18%, 95% C.I. 7%-29%), with a median duration of 8 weeks (range 5-19), with the complete remission lasting 1 yr. Hematologic toxicity was dose-limiting; W.H.O. greater than or equal to 3 values were observed for WBC in 36%, and for platelets in 26% of patients. The non hematologic toxicity included nausea and vomiting (90%), a flu-like syndrome (49%), diarrhea (35%), pain in the infused vein (28%) and hypotensive episodes (4%). Intermittent high-dose DTIC is active in advanced soft-tissue sarcoma and should be considered for inclusion in combination regimens. PMID- 1868028 TI - Combination of etoposide, adriamycin and cisplatin (EAP) in gastric cancer: association with severe toxicity. PMID- 1868029 TI - Combination of etoposide, adriamycin and cisplatin (EAP) in gastric cancer: association with severe toxicity. PMID- 1868030 TI - A new growth-regulated complementary DNA with the sequence of a putative trans activating factor. AB - A new complementary DNA (cDNA) clone has been isolated by differential screening of a cDNA library. The cognate RNA of this clone, called SC1, is growth regulated in human, mouse, and hamster cell lines. Its kinetics of growth regulation (time of increase in mRNA levels, sensitivity to cycloheximide, behavior in G1-specific temperature-sensitive mutants) classify the SC1 gene as a late growth-regulated gene, like the histone genes and the genes coding for the proteins of the DNA synthesis apparatus. By run-on assay, there is a modest increase in transcriptional rates after serum stimulation, which is not sufficient to explain the sharp increase in mRNA levels. The SC1 gene localizes to human chromosome 6p21-22. In bacteria, the SC1 cDNA clone makes a protein of Mr 39,000, in agreement with the putative reading frame. The amino acid sequence derived from the cDNA sequence indicates a previously unknown gene with a domain strongly suggestive of a trans-activating domain. The SC1 gene can be considered as coding for a possible new trans-activating factor that could play an important role in the transcription of genes required for the later stages of cell cycle progression. PMID- 1868031 TI - 1 alpha,25-dihydroxyvitamin D3-induced regulation of protein kinase C gene expression during HL-60 cell differentiation. AB - The human promyelocytic leukemia cell line HL-60 differentiates in vitro when treated with various inducers. It has previously been shown that protein kinase C (PKC) isozymes are modulated during granulocytic differentiation of HL-60 cells induced by dimethyl sulfoxide or retinoic acid (M. Makowske, R. Ballester, Y. Cayre, and O.M. Rosen, J. Biol. Chem., 263: 3402-3410, 1988; K. Hashimoto, A. Kishimoto, H. Aihara, I. Yasuda, K. Mikawa, and Y. Nishizuka, FEBS Left., 263: 31 34, 1990). HL-60 responds to 1 alpha, 25-dihydroxyvitamin D3 (1,25-(OH)2D3) or to 12-O-tetradecanoylphorbol-13-acetate by giving rise to monocytic cells. In the present study, we demonstrate that treatment of HL-60 cells with 1,25-(OH)2D3 causes dramatic increases in PKC-alpha and PKC-beta protein levels detected by immunoblotting with PKC isoform-specific antibodies and in Ca(2+)- and phospholipid-dependent protein kinase activity. We also observed a transient increase in the steady-state levels of PKC-alpha and PKC-beta mRNA species in Northern blotting experiments, with maximal induction occurring 48 h after addition of 1,25-(OH)2D3. Analyses of 1,25-(OH)2D3-induced PKC mRNA expression by nuclear run-on transcription experiments suggest that the observed increases in PKC mRNA levels may occur by a posttranscriptional mechanism(s). In contrast to the transient increases in PKC mRNA levels, the increases in PKC Mr 80,000 protein species and in PKC enzyme activity were progressive in HL-60 cells treated with 1,25-(OH)2D3 between 1 and 5 days, thus implying the existence of a further up-regulation of PKC proteins occurring at the translational and/or posttranslational levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868032 TI - Molecular assignment of a translocation breakpoint in acute myeloid leukemia with t(8;21). AB - An 8;21 translocation is a common chromosome abnormality associated with acute myeloblastic leukemia with maturation (M2 of French-American-British (FAB) classification). We have isolated chromosome 21 Notl linking clones; pulsed field gel electrophoresis analysis with one clone (LL263) detected an altered fragment of Notl-digested leukemic cell DNA carrying t(8;21). The altered fragment was shown to be produced by the 8;21 translocation. The breakpoint in chromosome 21 was located about 13 kb to 100 kb proximal to the LL263 Notl site. Because the LL263 clone has a CpG island and is a short distance from the breakpoint, the clone itself may be considered as a candidate for part of the t(8;21) associated gene. PMID- 1868033 TI - Cytogenetic analysis of 434 consecutively ascertained specimens of non-Hodgkin's lymphoma: correlations between recurrent aberrations, histology, and exposure to cytotoxic treatment. AB - Cytogenetic abnormalities in non-Hodgkin's Lymphoma (NHL) provide a model system for the analysis of the role of multiple genomic aberrations in human malignancy. In order to define correlations with histology, tumor evolution, and the effects of genotoxic exposure, cytogenetic analysis was performed on 434 specimens of NHL derived from 423 patients consecutively ascertained over a 5-year period (1984 1989). Six recurring translocations (RT) were observed: t(14;18)(q32;q21), t(8;14)(q24;q32), t(11;14)(q13;q32), t(3;22)(q27;11), t(2;5)(p23;q35), and t(1;6)(q21;q25). No translocation was specific to a single histologic subtype. Other structural chromosome abnormalities were analyzed according to break site; groups of related breaks were considered together for statistical analysis. Recurring other structural and numerical aberrations (ROA) encountered in greater than 10% of specimens included rearrangements with breaks at bands 1p32-36, 1q21 23, 6q21-25, and trisomies of chromosomes 7 and 12. ROA with one of these breaks or numerical abnormalities were the sole abnormalities in at least two cases. Correlations were observed among ROA and between ROA and histologic subtypes. Trisomy 7, breaks at 1q21-23, 1p32-36, 6q21-25, and 7q32 were associated with t(14;18); trisomy 18 was associated with trisomy 3; and structural abnormalities of chromosome 17 were associated with breaks at 1p32-36 and 6q21-25. Trisomy 7 and trisomy 12 were more frequent in t(14;18)-bearing intermediate to high grade tumors compared to low grade tumors. Trisomy 12 and breaks at band 1p22 were associated with large cell diffuse lymphomas. Incidence rates of reciprocal translocations, ROA, and measures of karyotypic complexity, including number of breakpoints and marker chromosomes were compared in pretreatment and posttreatment samples. Karyotypic complexity was greater in the posttreatment samples, reflecting an increased frequency of nonrecurring and low incidence aberrations. These results better define the association of genomic aberrations and tumorigenesis, histologic transformation, and tumor progression. PMID- 1868034 TI - Chromosome abnormalities in breast fibroadenomas. AB - A cytogenetic study on 25 breast fibroadenomas from 17 women is reported. Seven tumors in five patients showed clonal structural chromosome changes. In three patients the breaks involved chromosome 12, occurring in two tumors in band 12p12 and in band 12q15 in all three tumors of one patient. The finding of an identical aberration, t(11;12)(q21;q15), in three adenomas from the same patient strongly suggests a clonal origin of multiple fibroadenomas of the breast. PMID- 1868035 TI - t(18;22)(q21;q11) with rearrangement of BCL2 as a possible secondary change in a lymphocytic lymphoma. AB - We report a lymphocytic lymphoma showing a combination of two characteristic neoplasia-associated chromosomal changes: trisomy 12, commonly observed in chronic lymphocytic leukemia and lymphocytic lymphoma, and t(18;22)(q21;q11), a variant form of the t(14;18)(q32;q21) found in most follicular lymphomas. Southern blot analysis was performed using probes for the 5' end of the BCL2 gene (18q21) and for the J lambda as well as C lambda immunoglobulin genes (22q11). With these two probes, a unique rearranged fragment was detected. Thus the t(18;22)(q21;q11) can be considered as a variant translocation of t(14;18)(q32;q21). The karyotypic analysis supports the assumption that in our case trisomy 12 occurred first, and t(18;22) appeared during tumor progression as part of the clonal evolution. This is at variance with the typical t(14;18), which has never been found to occur as a secondary change. PMID- 1868036 TI - Localization of the HST/FGFK gene with regard to 11q13 chromosomal breakpoint and fragile site. AB - The HST/FGFK gene, a member of the fibroblast growth factor gene family and a protooncogene, is localized on chromosomal band 11q13. Genes in this region are frequently involved in hematopoietic and solid tumors. Here we show that the HST gene lies telomeric to the BCL1 gene, the t(11;14)(q13;q32) breakpoint, and the FRA11A rare fragile site. PMID- 1868037 TI - Deletion mapping of chromosomes 8, 10, and 16 in human prostatic carcinoma. AB - In an allelotyping study prostatic carcinoma, we found the highest frequency of allelic deletions on chromosomes 8, 10, 16, and 18. In all cases with allelic deletions, at least one of the chromosomes 8, 10, and 16 were involved. A detailed deletion mapping of these chromosomes in 18 cases was carried out with probes that detect restriction fragment length polymorphisms (RFLP) on chromosomes 8 (6 probes), 10 (11 probes), and 16 (9 probes). The highest frequency of allelic deletions were found on 8p (65%), where the minimally deleted region was between the PLAT locus and pter. The long arm of chromosome 16 had allelic deletions in 56% of informative cases, with three different break points, the most distal being located between D16S4 and D16S7. Chromosome 10 exhibited a complex deletion pattern with terminal deletions of the p or the q arm (2 cases each), a deletion pattern that could be interpreted as nonreciprocal translocations of the q arm (2 cases), or allelic losses on all informative loci, suggesting monosomy (2 cases). Our data suggest that tumor suppressor genes involved in the oncogenesis of prostatic carcinoma may be localized between 8 pter and the PLAT locus and that additional/alternative tumor suppressor genes may be localized on chromosome 10 and on the long arm of chromosome 16 distal to the D16S4 locus. PMID- 1868038 TI - Specific chromosome change associated with acquisition in vivo of tumorigenicity in carcinogen-induced rat urinary bladder carcinoma cells. AB - The correlation between chromosomal changes and tumorigenic potential of rat bladder epithelial cells was investigated. Seven cell lines were established from neoplastic urothelial cells derived from heterotopically transplanted rat bladders treated with topical application of one of two carcinogens, N-methyl-N nitrosourea (MNU) or N-hydroxy-N-glucuronosyl-2-aminofluorene. Loss of the short arm of chromosome 3 was demonstrated in three of four lines tumorigenic in the nude mouse, but in none of three nontumorigenic lines. One of the three nontumorigenic cell lines (D44c) was treated further in vitro with MNU. All six tumorigenic, but none of the four nontumorigenic, morphologically altered cell lines derived from D44c demonstrated loss of the short arm of chromosome 3. These results suggest that chromosome 3 alterations may be associated with the tumorigenicity of carcinogen-induced rat bladder epithelial cells. PMID- 1868039 TI - Trisomy 8 as the only chromosome change in an epithelioid smooth muscle tumor. AB - Epithelioid smooth muscle tumor is a rare low grade malignancy that usually occurs in the gastrointestinal tract. No chromosome studies of this tumor have been reported so far. We found trisomy 8 as the sole chromosome anomaly in a large hepatic epithelioid smooth muscle tumor. PMID- 1868040 TI - Common expression of melanoma tumor-associated antigens recognized by human tumor infiltrating lymphocytes: analysis by human lymphocyte antigen restriction. AB - Major histocompatibility complex (MHC) class I antigens (Ag), particularly human lymphocyte antigen (HLA)-A2, have been shown to function as restriction elements in human cytotoxic T lymphocyte recognition of tumor. This study was undertaken to determine the function of non-A2 MHC class I Ag in tumor recognition by tumor infiltrating lymphocytes (TILs) cultured from six melanomas, and to find evidence for shared or unique tumor-associated Ag. Four predominantly CD8+ and two mixed CD4+, CD8+ population TIL cultures were tested for lysis in short-term 51Cr release assays against a panel of targets including 29 fresh melanomas, 2 fresh sarcomas, 11 cultured melanoma lines, and 14 nonmelanoma cell lines derived from HLA-typed patients. All six melanoma TILs lysed the autologous melanoma. Two of three TILs from HLA-A2+ patients lysed allogeneic melanomas matched for HLA-A2, giving evidence for shared tumor Ag; one of these TILs also used HLA-B44 as a restriction element. The third HLA-A2+ TIL lysed autologous melanoma but not autologous Epstein-Barr virus-transformed B cells nor 14 HLA-A2 matched allogeneic melanomas, suggesting the possibility of a unique tumor Ag in this system. The three HLA-A2- TILs each lysed multiple HLA-matched melanomas, using HLA-A24, HLA-A31, and HLA-Cw7 as restriction elements. Blocking of autologous and allogeneic melanoma lysis by TILs with mAb w6/32 (anti-MHC class I) and anti-CD3, as well as cold target inhibition assays, confirmed that specific interaction of the T-cell receptor with MHC class I Ag and the relevant tumor Ag on the target cell surface is required for tumor lysis. These data provide evidence for specific recognition of shared melanoma Ag by human TILs. PMID- 1868041 TI - A rapid in vitro cytotoxicity assay for the detection of tumor necrosis factor on human BT-20 cells. AB - This report describes a rapid, reproducible in vitro bioassay to quantitate the cytotoxic activity of human tumor necrosis factor-alpha using a human rather than murine cell line in the absence of metabolic inhibitors. The target cells are BT 20 (breast carcinoma) cultured at 39 degrees C in the presence of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) in 96-well microtiter plates for 2 days. Cytotoxicity is measured by the crystal violet dye uptake of the remaining viable cells. This bioassay is sensitive to 1.5 ng/ml of rHuTNF-alpha, with an assay range to 130 ng/ml. Samples spiked into human plasma are measurable from 0.5 to 150 ng/ml. The specificity of this cytotoxic effect on the BT-20 cell line was demonstrated using rHuTNF-alpha neutralizing antibodies. A panel of cytokines including interferons, interleukins, and tumor necrosis factors was also analyzed using this assay system. Of the cytokines assayed, only recombinant murine tumor necrosis factor-alpha and recombinant human tumor necrosis factor beta demonstrated measurable cytotoxic activity when assayed independently, while recombinant human interferon-gamma was the only cytokine to demonstrate greater than additive activity in combination with rHuTNF-alpha. The simplicity and reproducibility of this assay on a human cell line makes it useful for the routine determination of the biological activity of human tumor necrosis factor alpha. PMID- 1868042 TI - A naturally occurring 6-9-kilodalton interleukin-1 (IL-1) inhibitor prevents IL-1 mediated islet cytotoxicity but not IL-1-mediated suppression of insulin secretion. AB - Earlier studies have shown direct effects of interleukin-1 (IL-1) on isolated pancreatic islets. Coculture of isolated rat pancreatic islets with human rIL-1 beta for 6 days resulted in dose-dependent cytotoxicity (up to 100%) and suppression of insulin secretion (up to 88.5%). The cytotoxic effects of rIL-1 beta beta were blocked by the simultaneous presence of a naturally occurring 6-9 kilodalton (kDa) inhibitor of IL-1-induced T-cell proliferation. However, the ability of rIL-1 beta to suppress insulin secretion was not blocked by the 6-9 kDa inhibitor of IL-1 activity. This IL-1 inhibitor is produced by mononuclear cells and is resistant to pH 2, sensitive to heating at 56 degrees C for 30 min, has a pI of 4.5-5.6, and appears to be different from other recognized IL-1 inhibitors in both composition and mechanism of action. Unlike this IL-1 inhibitor, a monoclonal antibody specific for rIL-1 beta was able to neutralize both the islet cytotoxic and insulin modulatory effects of rIL-1 beta. These results demonstrate the use of an IL-1 inhibitor to prevent at least one mechanism of islet destruction, and suggest separate pathways for IL-1 mediated islet cytotoxicity and suppression of insulin secretion. PMID- 1868043 TI - In vitro and in vivo comparison of the activity of human lymphokine-activated killer (LAK) cells and adherent LAK cells. AB - The effectiveness of "standard" lymphokine-activated killer (LAK) cells, recovered after 6 days, and of "standard" adherent LAK (A-LAK) cells, recovered after 14 days of culture in the presence of recombinant interleukin-2 (rIL-2) from peripheral blood lymphocytes of 21 healthy donors, was assessed through comparison of their proliferation, surface markers, cytotoxic activity, lymphokine production, and antitumor activity. In the presence of rIL-2, plastic adherent precursors of A-LAK cells proliferated much better than those of "standard LAK" cells and expanded even more than 300-fold. However, the final cell recovery of A-LAK was always lower because of their very few precursors, and the total lytic units (LUs) generated in A-LAK cultures were always lower for the same reason. On the other hand, the lytic activity of each A-LAK cell was always higher than that of a LAK cell. This was particularly evident on day 6 of culture. Removal of nonadherent cells after the first 24 h culture resulted in a significant enrichment in CD3-CD56+ and CD8+CD56+ cells in A-LAK cells, with a marginal number of CD4+ cells. A significant direct correlation between LUs and A LAK CD3-CD56+ percentage was found. In the presence of rIL-2, A-LAK cells produced higher amounts of tumor necrosis factor-alpha and interferon-gamma than LAK cells, while only A-LAK cells produced IL-1 beta and small amounts of IL-4. Neither LAK nor A-LAK produced IL-2. In the absence of injections of IL-2, LAK and A-LAK cells were equally able to inhibit the growth of a human T-cell lymphoma in immunosuppressed nude mice. PMID- 1868044 TI - Maintenance of tumoricidal activity and susceptibility to reactivation of subpopulations of rat liver macrophages. AB - The liver macrophage population was fractionated according to cell size into three subpopulations by means of elutriation centrifugation. The total liver macrophage population and the three subpopulations were cultured and exposed to the immunomodulators muramyl dipeptide (MDP), in a free or liposome-encapsulated form, and/or lipopolysaccharide (LPS). The tumor cytotoxic activity thus induced in the populations, the preservation of this activity and the response to a second stimulus were studied. The in vitro induced cytolytic activity was determined by a radioactivity release assay, using C26 colon adenocarcinoma cells, labeled with [methyl-3H]thymidine, as target cells. MDP or LPS readily activated the total macrophage population in maintenance culture to a tumor cytotoxic state during the first 2 days after isolation. Four days after isolation, the activation induced with both MDP and LPS was strongly reduced. The small to intermediate-size macrophages could be activated to tumor cytotoxic activity with MDP for up to 3 days and with LPS for up to 4 days in culture. The large-size macrophages could only be activated up to day 2 in culture with MDP or LPS or both. The combination of MDP and LPS, however, induced all cell populations in a synergistic way to become cytolytic for up to 4 days in culture. With free MDP as an activator, the activated state decayed within 1 day to almost zero levels, but less rapidly in the small cells than in the large cells. With liposome-encapsulated MDP, the activated state was preserved considerably longer, except in the largest cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868045 TI - Phase II trial of high-dose interleukin-2 and lymphokine-activated killer cells in Hodgkin's disease and non-Hodgkin's lymphoma. AB - Interleukin-2 (IL-2) plus lymphokine-activated killer (LAK) cell therapy has antineoplastic activity in renal cancer and malignant melanoma. In order to explore the activity of this therapy in Hodgkin's disease and non-Hodgkin's lymphoma, the Extramural IL-2/LAK Working Group (ILWG) treated 27 patients on two protocols using high-dose IL-2 and autologous LAK cells. Two of 12 patients with Hodgkin's disease experienced partial responses lasting 6 and 12 weeks. No patient with non-Hodgkin's lymphoma responded (p = NS). The toxicities of therapy were similar to those reported by the ILWG from trials of IL-2/LAK in solid tumors, consisting of transient hemodynamic, cardiopulmonary, renal and hepatic dysfunction, skin rash, fever, and flu-like symptoms. In view of the low response rate and the brief duration of these responses, we do not recommend the regimens reported here for further investigation in Hodgkin's disease or non-Hodgkin's lymphomas. PMID- 1868046 TI - Unusual gastrointestinal complications of interleukin-2 therapy. AB - Minor and reversible gastrointestinal side effects are common when patients receive interleukin-2 (IL-2) with or without lymphokine-activated killer (LAK) cells. We treated 42 cancer patients with IL-2 therapy and 3 patients developed serious gastrointestinal problems during treatment. Complications included sigmoid colon perforation, ischemic necrosis of the small and large intestine, and diffuse bowel ulceration. These were not associated with tumor implants or hypotension. Two patients died as a direct result of these problems despite aggressive surgical and medical management. The incidence of major gastrointestinal complications with IL-2 therapy may be greater than previously reported and a heightened awareness of potential gastrointestinal problems may circumvent considerable morbidity and mortality. PMID- 1868047 TI - Biological thiols elicit prolactin proteolysis by glandular kallikrein and permit regulation by biochemical pathways linked to redox control. AB - Rat glandular kallikrein (GK), a trypsin-like serine protease, cleaves rat prolactin (PRL) in vitro to novel forms detectable in vivo and likely to be of physiological significance. PRL proteolysis by GK is thiol-dependent, with thiols acting upon PRL to refold the molecule into novel conformations that are GK substrates. This study compared several natural and synthetic thiols for their ability to elicit PRL proteolysis by GK. Rat PRL was incubated with rat GK in the presence of various thiols and 0.5% Triton X-100, which enhances thiol-elicited proteolysis. Cleavage was analyzed by gel electrophoresis under reducing and nonreducing conditions. In the presence of Triton X-100, all low molecular weight thiols elicited PRL cleavage by GK. The order of potency was dithiothreitol greater than mercaptoethanol greater than lipoic acid greater than cysteamine = glutathione (GSH) = coenzyme A greater than cysteine. In the absence of Triton, however, dithiothreitol, coenzyme A, and mercaptoethanol were most effective in eliciting GK proteolysis. Triton X-100 enhanced PRL cleavage by 4-19-fold, depending upon the thiol used. Folding isomers of processed PRL observed following cleavage included disulfide-liked homodimers, oxidized monomers, reduced monomers and mixed disulfides; the folding isomers generated varied depending upon the thiol used. GSH potency in eliciting PRL proteolysis increased 10-fold in the presence of biochemical pathways shuttling reducing equivalents to GSH disulfide (GSSG). PRL cleavage by GK could be controlled by substrates, enzymes, and cofactors making up the reducing shuttle when GSSG was used. Thioredoxin (a protein disulfide oxidoreductase) potently elicited PRL proteolysis by GK in the presence of a reducing shuttle and Triton X 100.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868048 TI - Conformational studies of a peptide corresponding to a region of the C-terminus of ribonuclease A: implications as a potential chain-folding initiation site. AB - Conformational properties of the OT-16 peptide, the C-terminal 20 amino acids of RNase A, were examined by nonradiative energy transfer. A modified OT-16 peptide was prepared by solid-phase synthesis with the inclusion of diaminobutyric acid (DABA) at the C-terminus. The OT-16-DABA peptide was labeled with a fluorescent 1,5-dimethylaminonaphthalene sulfonyl (dansyl, DNS) acceptor at the N-terminal amine and a fluorescent naphthoxyacetic acid (NAA) donor at the gamma-amine of the DABA located at the C-terminus of the peptide by using an orthogonal protection scheme. Energy transfer was monitored in DNS-OT-16-DABA-NAA by using both fluorescence intensity (sensitized emission) and lifetime (donor quenching) experiments. The lifetime data indicate that the peptide system is a dynamic, flexible one. A detailed analysis, based on a dynamic model that includes a skewed Gaussian function to model the equilibrium distribution of interprobe distances and a mutual diffusion coefficient between the two probes to model conformational dynamics in the peptide [Beechem & Haas (1989) Biophys. J. 55, 1225.], identified the existence of a partially ordered structure (relatively narrow distribution of interprobe distances) at temperatures greater than or equal to 20 degrees C in the absence of denaturant. The width and the position of the average of the distributions decrease with increasing temperature, in this range; this suggests that the structure is stabilized by hydrophobic interactions. In addition, the peptide undergoes cold denaturation at around 1.5 degrees C as indicated by broadening of the distance distribution. The addition of 6 M guanidine hydrochloride (Gdn-HCl) also broadens the distance distribution significantly, presumably by eliminating the hydrophobic interactions and unfolding the peptide. The results of the analysis of the distance distribution demonstrate that (1) nonradiative energy transfer can be used to study the conformational dynamics of peptides on the nanosecond time scale, (2) a partially ordered structure of OT-16-DABA exists in solution under typical refolding conditions, and (3) structural constraints (presumably hydrophobic interactions) necessary for the formation of a chain-folding initiation site in RNase A are also present in the OT-16-DABA peptide in the absence of denaturant and are disrupted by Gdn-HCl. PMID- 1868049 TI - Transient intermediates in the folding of dihydrofolate reductase as detected by far-ultraviolet circular dichroism spectroscopy. AB - The kinetics of the reversible folding and unfolding of Escherichia coli dihydrofolate reductase have been studied by stopped-flow circular dichroism in the peptide region at pH 7.8 and 15 degrees C. The reactions were induced by concentration jumps of a denaturant, urea. The method can detect various intermediates transiently populated in the reactions although the equilibrium unfolding of the protein is apparently approximated by a two-state reaction. The results can be summarized as follows. (1) From transient circular dichroism spectra measured as soon as the refolding is started, a substantial amount of secondary structure is formed in the burst phase, i.e., within the dead time of stopped-flow mixing (18 ms). (2) The kinetics from this burst-phase intermediate to the native state are multiphasic, consisting of five phases designated as tau 1, tau 2, tau 3, tau 4, and tau 5 in increasing order of the reaction rate. Measurements of the kinetics at various wavelengths have provided kinetic difference circular dichroism spectra for the individual phases. (3) The tau 5 phase shows a kinetic difference spectrum consistent with an exciton contribution of two aromatic residues in the peptide CD region. The absence of the tau 5 phase in a mutant protein, in which Trp 74 is replaced by leucine, suggests that Trp 74 is involved in the exciton pair and that the tau 5 phase reflects the formation of a hydrophobic cluster around Trp 74. From the similarity of the kinetic difference spectrum to the difference between the native spectra of the mutant and wild-type proteins, it appears that Trp 47 is the partner in the exciton pair and that the structure formed in the tau 5 phase persists during the later stages of folding. (4) The later stages of folding show kinetic difference spectra that can be interpreted by rearrangement of secondary structure, particularly the central beta sheet of the protein. The pairwise similarities in the spectrum between the tau 3 and tau 4 phases, and between the tau 1 and tau 2 phases, also suggest the presence of two parallel folding channels for refolding. (5) The unfolding kinetics show three to four phases and are interpreted in terms of the presence of multiple native species. The total ellipticity change in kinetic unfolding reaction, however, agrees with the ellipticity difference between the native and unfolding states, indicating the absence of the burst phase in unfolding.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1868050 TI - Self-association of human and porcine relaxin as assessed by analytical ultracentrifugation and circular dichroism. AB - The self-association properties of recombinant DNA derived human relaxin, and porcine relaxin isolated from porcine ovaries, have been studied by sedimentation equilibrium analytical ultracentrifugation and circular dichroism (CD). The human relaxin ultracentrifuge data were adequately defined by a monomer-dimer self association model with an association constant of approximately 6 x 10(5) M-1, whereas porcine relaxin was essentially monomeric in solution. An approximate 5 fold increase in weight fraction of human relaxin monomer elicited by dilution of the protein resulted in no change in the far-UV CD spectrum at 220 nm. In contrast, after the same increase in weight fraction of monomer, the near-UV circular dichroism spectra for human relaxin exhibited a significant decrease in the amplitude for the CD bands near 277 and 284 nm. These CD bands, which may be assigned to the lone tyrosine in human relaxin, are superimposed on a broad envelope that is probably due to the three disulfide chromophores. Although both the human and porcine proteins contain two tryptophan residues, the near-UV CD spectra exhibit only a broad shoulder near 295 nm rather than the strong CD bands often found for tryptophan. Moreover, there is little change in this broad band after dilution of human relaxin to concentrations that resulted in a 4-fold increase in monomer weight fraction. These data suggest that dissociation of the human relaxin dimer to monomer is not accompanied by large overall changes in secondary structure or alteration in the average tryptophan environment, whereas there is a significant change in the tyrosine environment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868051 TI - 1H and 15N NMR resonance assignments and preliminary structural characterization of Escherichia coli apocytochrome b562. AB - The 1H and 15N resonances of uniformly enriched apocytochrome b562 (106 residues) have been assigned. The assignment work began with the identification of the majority of HN-H alpha-H beta subspin systems in two-dimensional DQF-COSY and TOCSY spectra of unlabeled protein in D2O and in 95% H2O/5% D2O buffer. Intraresidue and interresidue NOE connectivities were then searched for in two dimensional homonuclear NOESY spectra recorded on unlabeled protein and in the three-dimensional NOESY-HMQC spectrum recorded on uniformly 15N-enriched protein. Those data, combined with the main-chain-directed assignment strategy (MCD), led to the assignment of the main-chain and many side-chain resonances of 103 of the 106 residues. Qualitatively, the helical conformation is found to be the dominant secondary structure in apocytochrome b562 as it is in holocytochrome b562. The helical segments in apocytochrome b562 overlap extensively with the helical regions defined in the crystal structure of ferricytochrome b562. In addition, a number of tertiary NOEs have been identified which indicate that the global fold of the apoprotein at least partially resembles the four-helix bundle of the holoprotein. The results presented here, together with the evidence obtained with other methods [Feng and Sligar (1991) Biochemistry (submitted)], support the notion that the interior of the protein is fluid and may correspond to a molten globule state. PMID- 1868052 TI - Bilayer/cytoskeleton interactions in lipid-symmetric erythrocytes assessed by a photoactivable phospholipid analogue. AB - Two mechanisms have been proposed for maintenance of transbilayer phospholipid asymmetry in the erythrocyte plasma membrane, one involving specific interactions between the aminophospholipids of the inner leaflet of the bilayer and the cytoskeleton, particularly spectrin, and the other involving the aminophospholipid translocase. If the former mechanism is correct, then erythrocytes which have lost their asymmetric distribution of phospholipids should display altered bilayer/cytoskeleton interactions. To test this possibility, normal erythrocytes, erythrocytes from patients with chronic myelogenous leukemia or sickle disease, and lipid-symmetric and -asymmetric erythrocyte ghosts were labeled with the radioactive photoactivable analogue of phosphatidylethanolamine, 2-(2-azido-4-nitrobenzoyl)-1-acyl-sn-glycero-3 phospho[14C]ethanolamine ([14C]AzPE), previously shown to label cytoskeletal proteins from the bilayer. The labeling pattern of cytoskeletal proteins in pathologic erythrocytes and lipid-asymmetric erythrocyte ghosts was indistinguishable from normal erythrocytes, indicating that the probe detects no differences in bilayer/cytoskeleton interactions in these cells. In contrast, in lipid-symmetric erythrocyte ghosts, labeling of bands 4.1 and 4.2 and actin, and to a lesser extent ankyrin, by [14C]AzPE was considerably reduced. Significantly, however, labeling of spectrin was unaltered in the lipid-symmetric ghosts, suggesting that its relationship with the bilayer is normal in these lipid symmetric cells. These results do not support a model in which spectrin is involved in the maintenance of an asymmetric distribution of phospholipids in erythrocytes. PMID- 1868053 TI - Interaction of cholesterol with sphingomyelin in bilayer membranes: evidence that the hydroxy group of sphingomyelin does not modulate the rate of cholesterol exchange between vesicles. AB - Cholesterol undergoes exchange between membranes containing sphingomyelin at a much slower rate than between membranes lacking sphingomyelin. To investigate the role of the hydroxy group at the 3-position of sphingomyelin in the interaction between sphingomyelin and cholesterol, we have measured the rates of [4 14C]cholesterol exchange between unilamellar vesicles prepared with N stearoylsphingomyelin or with synthetic analogues in which the hydroxy group is replaced with an O-alkyl group or with hydrogen. Vesicles prepared from 3-deoxy- and 3-O-methyl-N-stearoylsphingomyelin had the same rate of [14C]-cholesterol desorption. The half-times for exchange from vesicles prepared with 3-O-methyl- and 3-deoxy-N-stearoylsphingomyelins and 10 mol % of cholesterol were only slightly faster (a factor of only 1.5) than that found from vesicles prepared from N-stearoylsphingomyelin and 10 mol % cholesterol. The rate of cholesterol desorption from vesicles could be accelerated by preparing vesicles from bulky 3 O-alkyl analogues of sphingomyelin. Vesicles containing 3-O-ethyl-N stearoylsphingomyelin and 3-O-tetrahydropyranyl egg sphingomyelin gave rate enhancements of approximately 14 and 35, compared with the rates observed in vesicles made from N-stearoyl- and egg sphingomyelin, respectively. These data indicate that insertion of sterically bulky groups at the 3-position of sphingomyelin (such as ethoxy and tetrahydropyranyloxy) in place of hydroxy interferes markedly with the molecular packing of cholesterol and sphingomyelin in bilayer membranes; however, the hydroxy group of sphingomyelin is not critical for the strong interaction of cholesterol with sphingomyelin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868054 TI - Structural elucidation and antigenicity of a novel phenolic glycolipid antigen from Mycobacterium haemophilum. AB - The structure of a novel antigenic glycolipid that distinguishes the opportunistic pathogen Mycobacterium haemophilum from all other mycobacteria was established by a series of degradation reactions leading to products that were analyzed by gas/liquid chromatography-mass spectrometry. The complete structure of the oligosaccharide unit was determined as 2,3-di-O-CH3-alpha-L-Rhap(1----2)3 O-CH3-alpha-L-Rhap(1----4 )-2,3-di-O-CH3-alpha-L-Rhap(1----. The lipid portion of the phenolic glycolipid was composed of two component phenolphthiocerols differing by two methylene groups, as determined by analysis of their per-O trideuteriomethylated derivatives. The diol unit of the phenolphthiocerols has a threo relative configuration. The absolute stereochemistry of the asymmetric centers of the phenolphthiocerols is uncertain, but the centers are probably 3R, 4S, 9R, and 11R as found for phthiocerol A from Mycobacterium tuberculosis. The hydroxyl functions of the branched glycolic chain are esterified to a complex mixture of multi-methyl branched mycocerosic acids, C27, C30, C32, C34, and C37 with molecular weights (as methyl esters) of 424, 466, 494, 522, and 564, respectively. The stereochemistry of the methyl branches of the mycocerosates have R absolute configuration. The glycolipid is highly antigenic and appears to be specific for M. haemophilum. There are intriguing similarities between the product from M. haemophilum and the well-known phenolic glycolipid I of Mycobacterium leprae, a matter that is discussed. PMID- 1868055 TI - pH dependency of the reactions catalyzed by chorismate mutase-prephenate dehydrogenase from Escherichia coli. AB - The variation with pH of the kinetic parameters associated with the mutase and dehydrogenase reactions catalyzed by chorismate mutase-prephenate dehydrogenase has been determined with the aim of elucidating the role that ionizing amino acid residues play in binding and catalysis. The pH dependency of log V for the dehydrogenase reaction shows that the enzyme possesses a single ionizing group with a pK value of 6.5 that must be unprotonated for catalysis. This same group is observed in the V/Kprephenate, as well as in the V/KNAD, profile. The V/Kprephenate profile exhibits a second ionizing residue with a pK value of 8.4 that must be protonated for the binding of prephenate to the enzyme. For the mutase reaction, the V/Kchorismate profile indicates the presence of three ionizing residues at the active site. Two of these residues, with similar pK values of about 7, must be protonated, while the third, with a pK value of 6.3, must be unprotonated. It can be concluded that all three groups are concerned with the binding of chorismate to the enzyme since the maximum velocity of the mutase reaction is essentially independent of pH. This conclusion is confirmed by the finding that the Ki profile for the competitive inhibitor, (3-endo,8-exo)-8 hydroxy-2-oxabicyclo[3.3]non-6-ene-3,5-dicarboxylic acid, shows the same three ionizing groups as observed in the V/Kchorismate profile. By contrast, the Ki profile for carboxyethyldihydrobenzoate shows only one residue, with a pK value of 7.3, that must be protonated for binding of the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868056 TI - Kinetic studies on chorismate mutase-prephenate dehydrogenase from Escherichia coli: models for the feedback inhibition of prephenate dehydrogenase by L tyrosine. AB - Kinetic studies have been undertaken to elucidate the mechanism of the allosteric inhibition by tyrosine of the prephenate dehydrogenase activity of the bifunctional dimeric enzyme chorismate mutase-prephenate dehydrogenase. The effect of tyrosine on the initial velocity of the reactions in the presence of both prephenate and the alternative substrate, 1-carboxy-4-hydroxy-2-cyclohexene 1-propanoate, have been determined. In addition, investigations have been made of the effect of tyrosine on the inhibition of the reaction by the inhibitory analogues of prephenate, (4-hydroxyphenyl)pyruvate, and (carboxyethyl)-1,4 dihydrobenzoate. The results of the double inhibition experiments indicate clearly that the enzyme possesses a distinct allosteric site for the binding of tyrosine. The initial velocity data obtained with both substrates have been fitted to the rate equations that describe a wide range of models. From a comparison of the results obtained from studies with the two substrates, and with a knowledge of the value for the dissociation constant of the tyrosine-enzyme complex, definitive conclusions have been reached about the mechanism of the allosteric inhibition. It is concluded that tyrosine combines twice at allosteric sites and in an antisynergistic fashion, while prephenate reacts at both active sites of the dimeric enzyme as well as weakly at one of the allosteric sites. It appears that the latter is simple competition reaction that affects neither the binding of prephenate at the active site nor the rate of product formation. The model also predicts the formation of an active tyrosine-enzyme-prephenate complex that yields product at a much slower rate than does the enzyme-prephenate complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868057 TI - Site-directed mutagenesis of Escherichia coli aspartate aminotransferase: role of Tyr70 in the catalytic processes. AB - Site-directed mutagenesis of Tyr70 in the active site of Escherichia coli aspartate aminotransferase (AspAT) followed by kinetic studies has elucidated the roles of the hydroxyl group and benzene ring of Tyr70. X-ray crystallographic analysis showed that replacement of Tyr70 by Phe did not alter the active-site conformation of the enzyme. Comparison of the kinetic parameters of the four half transamination reactions (the pyridoxal 5'-phosphate form of the enzyme with L aspartate or L-glutamate and the pyridoxamine 5'-phosphate form with oxalacetate or 2-oxoglutarate) between the wild-type and [Tyr70----Phe]AspATs showed that the mutation increases the energy level of the transition state by 2 kcal.mol-1 for all the four substrates, suggesting some contribution of the hydroxyl group of Tyr70 to the transition state. When Phe70 was further replaced by Ser, the energy level of the transition state for L-glutamate or 2-oxoglutarate, but not for L aspartate or oxalacetate, was further increased by 2-3 kcal.mol-1, suggesting that the presence of a benzene ring at position 70 is essential for recognizing the L-glutamate-2-oxoglutarate pair as substrates. PMID- 1868058 TI - Effects of point mutations in a hinge region on the stability, folding, and enzymatic activity of Escherichia coli dihydrofolate reductase. AB - The role of a hinge region in the folding, stability, and activity of Escherichia coli dihydrofolate reductase was investigated with three site-directed mutants at valine-88, the central residue of the hinge. The three mutants, V88A and V88I and a valine-88 deletion, were created to perturb the packing of hydrophobic residues in the interior of a loose turn formed by residues 85-91. Deleting the valine-88 residue destabilized the protein by 2.93 +/- 0.6 kcal/mol as determined by equilibrium unfolding transitions in urea monitored by circular dichroism at 20 degrees C. Substitution of alanine for valine-88 stabilized the protein by -0.20 +/- 0.02 kcal/mol, and the isoleucine substitution was mildly destabilizing by 1.73 +/- 0.2 kcal/mol. Although there was no clear correlation between side-chain volume and stability, these results suggest that side-chain interactions in the interior of the turn influence the folding and stability of dihydrofolate reductase. The specific activity of the valine deletion mutant was approximately twice that of the wild-type protein while the specific activities of the V88A and V88I proteins were only slightly greater than the wild type. The full time courses of the reactions catalyzed by the mutants were almost identical with that for the wild type, indicating no major changes in the kinetic mechanism. Additionally, the rate constants associated with interconversion between various forms of the apoenzyme were identical for the mutant and wild-type enzymes. The rate constants for refolding transitions were examined by dilution of urea inactivated protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868059 TI - Secondary conformational polymorphism of nucleic acids as a possible functional link between cellular parameters and DNA packaging processes. AB - Circular dichroism and electron microscopy studies of various in vitro DNA packaging systems indicate that all the factors which induce and modulate the secondary conformation of DNA molecules are capable of eliciting nucleic acids condensation processes into tight, highly ordered tertiary structures as well as altering the extent of order and compactness within the resulting species. Specifically, such factors include the ionic strength, the presence of particular dehydrating agents and polyamines, as well as the pH values. It is proposed that slight alterations of these parameters induce the formation of short non-B-DNA segments that propagate as a perturbation along the B-DNA double helix. The structural fluctuations of the dsDNA molecules that result from the conformational discontinuities formed at the junction sites between the B motif and the conformationally altered segments alter the elastic response of the nucleic acids and facilitate cooperative condensation processes. Moreover, the type and frequency of the structurally modified clusters interspersed within the B conformation and determined by the environmental parameters are shown to provide a means for continuous regulation of the extent and mode of DNA packaging. The ionic strength and hydrophobic environment in the close vicinity of the DNA molecules are controlled and modulated in vivo by DNA-binding proteins such as histones and protamines; similarly, pH values and polyamine concentrations are constantly regulated in living systems. It is suggested, therefore, that the secondary structural polymorphism which characterizes the DNA molecules might display a regulatory role by acting as a functional link between cellular parameters and the extent, mode, and timing of nucleic acid packaging processes. PMID- 1868060 TI - Stimulation of transcript elongation requires both the zinc finger and RNA polymerase II binding domains of human TFIIS. AB - The eukaryotic transcriptional factor TFIIS enhances transcript elongation by RNA polymerase II. Here we describe two functional domains in the 280 amino acid human TFIIS protein: residues within positions 100-230 are required for binding to polymerase, and residues 230-280, which form a zinc finger, are required in conjunction with the polymerase binding region for transcriptional stimulation. Interestingly, a mutant TFIIS with only the polymerase binding domain actually inhibits transcription, whereas a mutant in which the polymerase binding and zinc finger domains are separated by an octapeptide is only weakly active. The zinc finger itself has no effect on transcription, but in contrast to the wild-type protein, it binds to oligonucleotides. These findings suggest that TFIIS may interact with RNA polymerase II such that the normally masked zinc finger can specifically contact nucleotides in the transcription elongation zone at a position juxtaposed to the polymerization site. PMID- 1868061 TI - Unusual low reactivity of the water oxidase in redox state S3 toward exogenous reductants. Analysis of the NH2OH- and NH2NH2-induced modifications of flash induced oxygen evolution in isolated spinach thylakoids. AB - The effect of redox-active amines NH2R (R = OH or NH2) on the period-four oscillation pattern of oxygen evolution has been analyzed in isolated spinach thylakoids as a function of the redox state Si (i = 0, ..., 3) of the water oxidase. The following results were obtained: (a) In dark-adapted samples with a highly populated S1 state, NH2R leads via a dark reaction sequence to the formal redox state "S-1"; (b) the reaction mechanism is different between the NH2R species; NH2OH acts as a one-electron donor, whereas NH2NH2 mainly functions as a two-electron donor, regardless of the interacting redox state Si (i = 0, ..., 3). For NH2NH2, the modified oxygen oscillation patterns strictly depend upon the initial ratio [S0(0)]/[S1(0)] before the addition of the reductant; while due to kinetic reasons, for NH2OH this dependence largely disappears after a short transient period. (c) The existence of the recently postulated formal redox state "S-2" is confirmed not only in the presence of NH2NH2 [Renger, G., Messinger, J., & Hanssum, B. (1990) in Current Research in Photosynthesis (Baltscheffsky, M., Ed.) Vol. 1, pp 845-848, Kluwer, Dordrecht] but also in the presence of NH2OH. (d) Activation energies, EA, of 50 kJ/mol were determined for the NH2R-induced reduction processes that alter the oxygen oscillation pattern from dark-adapted thylakoids. (e) Although marked differences exist between NH2OH and NH2NH2 in terms of the reduction mechanism and efficiency (which is about 20-fold in favor of NH2OH), both NH2R species exhibit the same order of rate constants as a function of the redox state Si in the nonperturbed water oxidase: kNH2R(S0) greater than kNH2R(S1) much less than kNH2R(S2) much greater than kNH2R(S3) The large difference between S2 and S3 in their reactivity toward NH2R is interpreted to indicate that a significant change in the electronic configuration and nuclear geometry occurs during the S2----S3 transition that makes the S3 state much less susceptible to NH2R. The implications of these findings are discussed with special emphasis on the possibility of complexed peroxide formation in redox state S3 postulated previously on the basis of theoretical considerations [Renger, G. (1978) in Photosynthetic Water Oxidation (Metzner, H., Ed.) pp 229 248, Academic Press, London]. PMID- 1868062 TI - Cell-permeable fluorescent indicator for cytosolic chloride. AB - A major limitation of quinolinium-based fluorescent indicators for cytosolic Cl- has been the necessity of invasive cell loading because the positively charged ring nitrogen confers high polarity and membrane impermeability. A novel approach to mask the positive nitrogen was developed and evaluated for rapid, noninvasive indicator loading into living cells and effective intracellular trapping. The nonpolar and lipophilic compound 6-methoxy-N-ethyl-1,2-dihydroquinoline (diH-MEQ) was Cl- insensitive but was readily oxidized to the membrane-impermeable and Cl( )-sensitive fluorescent indicator 6-methoxy-N-ethylquinolium chloride (MEQ), MEQ had 344-nm absorbance and 440-nm emission maxima, 0.70 quantum yield, and 4100 M 1 cm-1 molar extinction coefficient. In aqueous buffers, the fluorescence of MEQ was quenched by Cl- by a collisional mechanism with a Stern-Volmer constant (KCl) of 145 M-1. MEQ fluorescence was quenched by other anions (KBr = 275 M-1, KI = 360 M-1, KSCN = 300 M-1) but not by NO3-, SO4(2-), cations, and pH. Swiss 3T3 fibroblasts and colonic T84 cells were loaded with MEQ by incubation at 37 degrees C with 25-50 microM diH-MEQ for 5-10 min followed by diH-MEQ-free buffer for 15 min. MEQ stained cells brightly and uniformly and was nontoxic in studies of cell growth, cAMP and Ca2+ signaling, and electrophysiological properties. MEQ leaked out of cells by less than 10% in 60 min and was sensitive to cytosolic Cl- with KCl = 19 M-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868063 TI - Oxygenase side reactions of acetolactate synthase and other carbanion-forming enzymes. AB - Enzymes that mediate carbanion chemistry must protect their reactants from solvent and undesirable electrophiles, such as molecular oxygen. A number of enzymes that utilize carbanionic intermediates were surveyed for O2-consuming side reactions. Several of these enzymes, acetolactate synthase, pyruvate decarboxylase, class II aldolase, and glutamate decarboxylase, catalyze previously undetected oxygen-consuming reactions, while others such as class I aldolase, [(phosphoribosyl)amino]imidazole carboxylase, 6-phosphogluconate dehydrogenase, isocitrate dehydrogenase, and triosephosphate isomerase do not. Prior to this work, only ribulosebisphosphate carboxylase was known to catalyze an oxygenase side reaction. These new example indicate that while O2-consuming side reactions are a more general feature of enzyme-mediated carbanion chemistry than has been previously appreciated, they are not necessarily an inevitable consequence of this chemistry. Expression of an oxygenase activity not only depends on the accessibility of the carbanionic intermediate to molecular oxygen but also may depend on the ability of the enzyme to stabilize the initially formed peroxide anion either through protonation with an appropriate enzymic group or through metal coordination. PMID- 1868064 TI - Reactivity of medium-chain acyl-CoA dehydrogenase toward molecular oxygen. AB - The free two-electron-reduced form of medium-chain acyl-CoA dehydrogenase is reoxidized by 120 microM molecular oxygen (50 mM phosphate buffer, pH 7.6, 2 degrees C) with a half-time of approximately 7 s. Reoxidation yields hydrogen peroxide as a major product with only traces of the superoxide anion. In contrast, enzyme reduced with octanoyl-CoA is extremely slowly reoxidized oxygen, and so a series of 14 different substrate analogues have been tested to assess the structural factors responsible for this effect. Complexes with redox-inactive ligands such as 3-thia- and 2-azaoctanoyl-CoA lead to an approximately 3000-fold slowing of the rate of reoxidation of the free dihydroflavin form of the enzyme. Comparable ligands lacking the thioester carbonyl function are much less effective with rates some 1.3-4-fold slower than the free enzyme. The strong suppression of oxygen reactivity observed with certain ligands is probably not simply a steric effect but may reflect desolvation of the active site and consequent destabilization of the superoxide anion intermediate formed during reoxidation of the flavin. The profound differences in oxygen reactivity between acyl-CoA dehydrogenase and acyl-CoA oxidase and the unusual stability of certain flavoprotein semiquinones in air are discussed in terms of these thermodynamic and kinetic arguments. PMID- 1868065 TI - Role of the four conserved histidine residues in the amidotransferase domain of carbamoyl phosphate synthetase. AB - Carbamoyl phosphate synthetase from Escherichia coli catalyzes the formation of carbamoyl phosphate from ATP, bicarbonate, and glutamine. The amidotransferase activity of this enzyme is catalyzed by the smaller of the two subunits of the heterodimeric protein. The roles of four conserved histidine residues within this subunit were probed by site-directed mutagenesis to asparagine. The catalytic activities of the H272N and H341N mutants are not significantly different than that of the wild-type enzyme. The H353N mutant is unable to utilize glutamine as a nitrogen source in the synthetase reaction or the partial glutaminase reaction. However, binding to the glutamine active site is not impaired in the H353N enzyme since glutamine is found to activate the partial ATPase reaction by 40% with a Kd of 54 microM. The H312N mutant has a Michaelis constant for glutamine that is 2 orders of magnitude larger than the wild-type value, but the maximal rate of glutamine hydrolysis is unchanged. These results are consistent with His-353 functioning as a general acid/base catalyst for proton transfers while His-312 serves a critical role for the binding of glutamine to the active site. PMID- 1868066 TI - Lyase activity of nucleoside 2-deoxyribosyltransferase: transient generation of ribal and its use in the synthesis of 2'-deoxynucleosides. AB - In the absence of acceptors nucleoside 2-deoxyribosyltransferase catalyzes the slow hydrolysis of 2'-deoxynucleosides. During this hydrolytic reaction, D-ribal (1,4-anhydro-2-deoxy-D-erythro-pent-1-enitol), a glycal of ribose hitherto encountered only as a reagent in organic synthesis, is generated spontaneously, disappearing later as 2'-deoxynucleoside hydrolysis approaches completion. Nucleoside 2-deoxyribosyltransferase is found to catalyze the hydration of D ribal in the absence of nucleic acid bases and the synthesis of deoxyribonucleosides from ribal in their presence, affording a new method for the preparation of 2'-deoxyribonucleosides. The stereochemistry of nucleoside formation from ribal supports the intervention of deoxyribosyl-enzyme intermediate. The equilibrium constant for the covalent hydration of ribal is found to be approximately 65. PMID- 1868067 TI - Linkage between proton binding and amidase activity in human alpha-thrombin: effect of ions and temperature. AB - The amidase activity of human alpha-thrombin has been studied at steady state in the pH range 6-10, as a function of NaCl concentration from 1 mM to 1 M and temperature from 10 to 40 degrees C. The Michaelis-Menten constant, Km, shows a bell-shaped dependence over this pH range with a minimum around pH 7.5 in the presence of 0.1 M NaCl at 25 degrees C. The catalytic constant, kcat, also has a bell-shaped pH dependence with multiple inflection points that are more evident at low NaCl concentrations and a maximum around pH 8.2 in the presence of 0.1 M NaCl at 25 degrees C. A detailed analysis of the results in terms of a general linkage scheme has allowed a thorough characterization of the linkage between proton and substrate binding and its dependence on NaCl concentration, as well as the relevant entropic and enthalpic contributions to binding and catalytic events. Formulation of detailed partition functions for each enzyme intermediate involved in the catalytic cycle suggests that (at least) three groups are responsible for the control of thrombin amidase activity as a function of pH. One group is to be identified with the active site His, due to its pK values in the free enzyme and the adduct and its enthalpy of ionization. The effect of NaCl concentration on amidase activity seems to be extremely specific. Comparative steady-state measurements carried out in the presence of NaCl, NaBr, NaI, KCl, and MgCl2 show that human alpha-thrombin is capable of discriminating among different cations and anions. This suggests that small ions participate as allosteric effectors in the regulation of thrombin activity. The linkage with NaCl is strongly pH dependent and increases with decreasing pH. The present results provide information on the basic aspects of human alpha-thrombin activity and regulation and enable a rigorous thermodynamic approach to other important regulatory interactions in human alpha-thrombin and its structurally perturbed derivatives. PMID- 1868068 TI - Mouse protein kinase C-delta, the major isoform expressed in mouse hemopoietic cells: sequence of the cDNA, expression patterns, and characterization of the protein. AB - A complementary DNA (cDNA) of 2559 bp which encode all 674 amino acids of mouse protein kinase C-delta (PKC-delta) has been isolated from a cDNA library prepared from ABPL-2, a mouse myeloid tumor. The library was screened with a partial PKC delta cDNA clone that had been created by polymerase chain reaction (PCR) amplification of ABPL-2 RNA using primers that are conserved among all rat PKC isozymes. This approach proved to be a distinct improvement over screening with synthetic oligonucleotides. Similar sets of cDNAs prepared from other hemopoietic cell lines were screened with this PKC-delta cDNA and with probes for the other PKC isoforms. These experiments revealed that the major isoform of PKC expressed in hemopoietic cells is PKC-delta. PKC-delta protein was purified from ABPL-3, a mouse myeloid tumor which expressed principally the delta isoform of PKC. The protein eluted from a hydroxylapatite column in the same position as PKC-beta and -epsilon would elute, if present. The kinase activity of purified PKC-delta showed strict dependence on the presence of phospholipids, but showed no activation by Ca2+. PMID- 1868069 TI - Glycolipid changes in murine myelogenous leukemias: neutral glycolipids as markers for specific populations of leukemias. AB - We have studied the glycolipid composition of six different murine myelogenous leukemias as well as that of T-cell leukemias and normal spleen cells. Neutral and acidic lipid fractions were isolated by column chromatography on DEAE Sephadex and analyzed by high-performance thin-layer chromatography (HPTLC) and an HPTLC overlay method. Murine myelogenous leukemias were found to contain globo and ganglio-series neutral glycolipids, e.g., glucosylceramide (Glc-cer), lactosylceramide (Lac-cer), globotriaosylceramide (Gb3), globoside (Gb4), Forssman glycolipid (Gb5), and asialo-GM1 (GA1). Monoblastic leukemia cells contained increased proportions of Gb3, Gb4, Gb5, and GA1. Monocytic and myelomonocytic leukemia cells contained increased proportions of Glc-cer and Lac cer. Especially, Glc-cer accounted for approximately 60% of the total neutral glycolipids in monocytic leukemia cells. Gb3 was the major neutral glycolipid in reticulum cell neoplasm type A, and it accounted for approximately 75% of the neutral glycolipids. GA1 was the major neutral glycolipid in myeloblastic and granulocytic leukemia cells as well as T-cell leukemias. Especially, granulocytic leukemia cells contained predominantly GA1, and it accounted for approximately 80% of the total neutral glycolipids. The pattern of gangliosides in myelogenous leukemias was more complex when compared with that of the neutral glycolipids; murine myelogenous leukemias contained at least 13 gangliosides, including such major gangliosides as GM1, GM1b containing N-acetyl neuraminic acid and N glycolyl neuraminic acid, and Ga1NAc-GM1b. Alterations of glycolipid composition in murine myeloid leukemias may be associated with cellular differentiation and maturation, and therefore these characteristic glycolipid species may be regarded as markers for specific populations of leukemia cells. PMID- 1868070 TI - Extensive segregation of acidic phospholipids in membranes induced by protein kinase C and related proteins. AB - Protein kinase C and two other proteins with molecular masses of 64 and 32 kDa, purified from bovine brain, constitute a type of protein that binds a large number of calcium ions in a phospholipid-dependent manner. This study suggested that these proteins also induced extensive clustering of acidic phospholipids in the membranes. Clustering of acidic phospholipids was detected by the self quenching of a fluorescence probe that was attached to acidic phospholipids (phosphatidic acid or phosphatidylglycerol). Addition of these proteins to phospholipid vesicles containing 15% fluorescently labeled phosphatidic acid dispersed in neutral phosphatidylcholine resulted in extensive, rapid, and calcium-dependent quenching of the fluorescence signal. Fluorescence-quenching requirements coincided with protein-membrane binding characteristics. As expected, the addition of these proteins to phospholipid vesicles containing fluorescent phospholipids dispersed with large excess of acidic phospholipids produced only small fluorescence changes. In addition, association of these proteins with vesicles composed of 100% fluorescent phospholipids resulted in no fluorescence quenching. Protein binding to vesicles containing 5-50% fluorescent phospholipid showed different levels of fluorescence quenching that closely resemble the behavior expected for extensive segregation of the acidic phospholipids in the outer layer of the vesicles. Thus, the fluorescence quenching appeared to result from self-quenching of the fluorophores that become clustered upon protein-membrane binding. These results were consistent with protein-membrane binding that was maintained by calcium bridges between the proteins and acidic phospholipids in the membrane. Since each protein bound eight or more calcium ions in the presence of phospholipid, they may each induce clustering of a related number of acidic phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868071 TI - Highly sequential binding of protein kinase C and related proteins to membranes. AB - Protein kinase C belongs to a class of proteins that displays simultaneous interaction with calcium and phospholipids. Other members of this class include two proteins (Mr 64K and 32K) isolated from bovine brain. The association of these proteins with membranes exhibited highly unusual properties that were not consistent with a simple equilibrium. Titration of protein-phospholipid binding as a function of calcium showed an apparently normal curve with a low degree of cooperativity. The binding was rapid and quickly adjusted to changes in the calcium concentration. Calcium was readily exchanged from the protein phospholipid complex. However, at each calcium concentration, membrane-bound protein was not in rapid equilibrium with free protein in solution; the half-time for dissociation exceeded 24 h. Titration of phospholipid vesicles with proteins showed different saturation levels of bound protein at different calcium concentrations. The amount of protein bound was almost entirely determined by the concentration of calcium and was virtually unaffected by the free protein concentration. These properties suggested that protein-phospholipid binding involved a sequence of steps that were each irreversible upon completion. These binding properties were consistent with high-affinity interaction between protein and phospholipid, high cooperativity with respect to calcium (N greater than or equal to 10), clustering of acidic phospholipids, and negative cooperativity with respect to protein density on the membrane. A major apparent problem with the complete titration of PKC-membrane interaction was a requirement for calcium in excess of intracellular levels. However, a highly sequential binding process showed that a number of protein-binding sites on the membrane would be saturated with calcium at physiological levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868072 TI - Binding and fluorescence studies of the relationship between neurophysin-peptide interaction and neurophysin self-association: an allosteric system exhibiting minimal cooperativity. AB - The mechanism of peptide-enhanced neurophysin self-association was investigated to address questions raised by the crystal structure of a neurophysin-dipeptide complex. The dependence on protein concentration of the binding of a broad range of peptides to the principal hormone-binding site confirmed that occupancy of this site alone, and not a site that bridges the monomer-monomer interface, is the trigger for enhanced dimerization. For the binding of most peptides to the principal hormone-binding site on bovine neurophysin I, the affinity of each dimer site was at least 10 times that of monomer under the conditions used. No interactions between the two sites of the dimer were evident. Fluorescence polarization studies of pressure-induced dimer dissociation indicated that the volume change for this reaction was almost 4 times greater in the liganded than in the unliganded state, pointing to a significant alteration of the monomer monomer interface upon peptide binding. Novel conformational changes in the vicinity of the single neurophysin tyrosine, Tyr-49, induced by pressures lower than required for subunit dissociation, were also observed. The bovine neurophysin I dimer therefore appears to represent an allosteric system in which there is thermodynamic and functional communication between each binding site and the monomer-monomer interface, but no communication across the interface to the binding site of the other subunit. A model for the peptide-enhanced dimerization is proposed in which intersubunit contacts between monomers reduce the large unfavorable free energy associated with binding-induced intrasubunit conformational change. Structural origins of the lack of communication across the interface are suggested on the basis of the low volume change associated with dimerization in the unliganded state and monomer-monomer contacts in the crystal structure. Potential roles for the peptide alpha-amino group and position 2 phenyl ring in triggering conformational change are discussed. PMID- 1868073 TI - Neutron and X-ray scattering studies on the human complement protein properdin provide an analysis of the thrombospondin repeat. AB - Properdin is a regulatory glycoprotein of the alternative pathway of the complement system of immune defense. It is responsible for the stabilization of the C3 convertase complex formed between C3b and the Bb fragment of factor B. Neutron and X-ray solution scattering experiments were performed on the dimeric and trimeric forms of properdin. These have RG values of 9.1 and 10.7 nm, respectively. The scattering curves were compared with Debye sphere modeling simulations for properdin. Good agreements were obtained for models similar to published electron micrographs showing that the properdin trimer has a triangular structure with sides of 26 nm. Such a structure also accounted for sedimentation coefficient data on properdin. Primary structure analyses for mouse and human properdin have shown that this contains six homologous motifs known as the thrombospondin repeat (TSR), which is the second most abundant domain type found in the complement proteins. Sequences for these 12 TSRs were aligned with 19 others found in thrombospondin and the late complement components. Three distinct groups of TSRs were identified, namely, the TSRs found in thrombospondin and properdin, the TSRs mostly found at the N-terminus of the late complement components, and the TSRs found at the C-terminus of the late components. Averaged secondary structure predictions suggested that all three groups contain similar backbone structures with two amphipathic turn regions and one hydrophilic beta strand region. The mean dimensions of the TSRs of properdin in solution were determined to be approximately 4 nm X 1.7 nm X 1.7 nm, showing that these are elongated in structure. PMID- 1868074 TI - Solution structure of pardaxin P-2. AB - Pardaxin is a mucosal secretion of the Pacific sole Pardachirus pavoninus that exhibits unusual shark repellent and surfactant properties [Thompson, S. A., Tachibana, K., Nakanishi, K., & Kubota, I. (1986) Science 233, 341-343]. This 33 amino acid polypeptide folds into ordered structures in trifluoroethanol-water solution and in micelles but adopts a random-coiled structure in water solution. The complete proton NMR spectrum of pardaxin P-2 has been assigned in CF3CD2OD/H2O (1:1) solution, and the three-dimensional structure has been elucidated with distance restrained molecular dynamics calculations. It is demonstrated that peptide segments within the 7-11 and 14-26 residue stretches are helical while residues at the C- and N-terminus exist predominantly in extended conformations in solution. The dipeptide 12-13 segment connecting the two helices exists as a bend or a hinge allowing the two helices to be oriented in a L-shaped configuration. These studies establish that pardaxin P-2 adopts a novel amphiphilic helix (7-11)-bend (12-13)-helix (14-26) motif with Pro-13 forming the focal point of the turn or bend between the two helices. PMID- 1868075 TI - Differential hydration of dA.dT base pairing and dA and dT bulges in deoxyoligonucleotides. AB - The role of water in the formation of stable duplexes of nucleic acids is being studied by determining the concurrent volume change, heats, and counterion uptake that accompany the duplexation process. The variability of the volume contraction that we have observed in the formation of a variety of homoduplexes suggests that sequence and conformation acutely affect the degree of hydration. We have used a combination of densimetric and calorimetric techniques to measure the change in volume and enthalpy resulting from the mixing of two complementary strands to form (a) fully paired duplexes with 10 or 11 base pairs and (b) bulged decameric duplexes with an extra dA or dT unmatched residue. We also monitored absorbance vs temperature profiles as a function of strand and salt concentration for all four duplexes. Relative to the decamer duplex, insertion of an extra dA.dT base pair to form an undecamer duplex results in a favorable enthalpy of -5.6 kcal/mol that is nearly compensated by an unfavorable entropy term of -5.1 kcal/mol. This enthalpy difference correlates with a differential uptake of water molecules, corresponding to an additional hydration of 16 mol of water molecules/mol of base pair. Relative to the fully paired duplexes, both bulged duplexes are 12-16 degrees C less stable and exhibit marginally larger counterion uptake on forming the duplex. The enthalpy change is slightly lower for the T-bulge duplex and less still for the A-bulge duplex. The volume change results indicate that an unmatched residue increases the amount of coulombic and/or structural hydration. The combined results strongly suggest that the destabilizing forces in bulged duplexes are partially compensated by an increase in hydration levels. PMID- 1868076 TI - DNA unwinding produced by site-specific intrastrand cross-links of the antitumor drug cis-diamminedichloroplatinum(II). AB - The DNA unwinding produced by specific adducts of the antitumor drug cis diamminedichloroplatinum(II) has been quantitatively determined. Synthetic DNA duplex oligonucleotides of varying lengths with two base pair cohesive ends were synthesized and characterized that contained site-specific intrastrand N7 purine/N7-purine cross-links. Included are cis-[Pt(NH3)2[d(GpG)]], cis [Pt(NH3)2(d(ApG)]], and cis-[Pt(NH3)2[d(GpTpG)]] adducts, respectively referred to as cis-GG, cis-AG, and cis-GTG. Local DNA distortions at the site of platination were amplified by polymerization of these monomers and quantitatively evaluated by using polyacrylamide gel electrophoresis. The extent of DNA unwinding was determined by systematically varying the interplatinum distance, or phasing, in polymers containing the adducts. The multimer that migrates most slowly gives the optimal phasing for cooperative bending, from which the degree of unwinding can be obtained. We find that the cis-GG and cis-AG adducts both unwind DNA by 13 degrees, while the cis-GTG adduct unwinds DNA by 23 degrees. In addition, experiments are presented that support previous studies revealing that a hinge joint forms at the sites of platination in DNA molecules containing trans GTG adducts. On the basis of an analysis of the present and other published studies of site-specifically modified DNA, we propose that local duplex unwinding is a major determinant in the recognition of DNA damage by the Escherichia coli (A)BC excinuclease. In addition, local duplex unwinding of 13 degrees and bending by 35 degrees are shown to correlate well with the recognition of platinated DNA by a previously identified damage recognition protein (DRP) in human cells. PMID- 1868077 TI - In vitro transcription analysis of DNA alkylation by nitrogen mustard. AB - A synchronized in vitro transcription assay has been used to probe the sequence specificity of alkylation of DNA by nitrogen mustard. Transcriptional blockages were detected with use of a 497-base-pair PvuII/SalI restriction fragment of a modified pBR322 vector when initiation of transcription was commenced after the DNA had been alkylated but not if the initiated transcription complex was subjected to alkylation before the elongation phase. The intensity of transcriptional blockages increased with alkylation time and was maximal after 1.5 h at a mustard concentration of 200 microM. There was also evidence of alkylation of the promoter region with increasing mustard concentration. The transcriptional blockage pattern changed at some sites as elongation time was increased and three types of blockages were observed-partial transcription (one or two nucleotides) past an initial blockage site, delayed but normal transcription past some sites, and complete termination at most sites. Eight of the nine blockage sites detected were at G or GG sequences on the template strand, with an apparent specificity for 5'-CTGT sequences of the template strand. Seven of the nine sites were capable of inter- or intrastrand cross links, including three possible G-G interstrand cross-links spanning an intervening base-pair. In the 103-bp segment probed by this procedure, transcriptional blockages were detected (with one exception) only at sites corresponding to G on the template strand where inter- or intrastrand cross linking was possible but not for similar sequences on the non-template strand. PMID- 1868078 TI - Posttranscriptional regulation of coumarin 7-hydroxylase induction by xenobiotics in mouse liver: mRNA stabilization by pyrazole. AB - The induction mechanism by pyrazole or phenobarbital of coumarin 7-hydroxylase (cytochrome P450coh) was investigated in DBA/2J male mice. The P450coh mRNA in the pyrazole-induced mice was increased gradually to a 20-fold higher level within 48 h, yet transcription of the P450coh gene was not affected. The half life of P450coh mRNA, on the other hand, was at least 4-fold longer in the pyrazole-induced DBA/2J (approximately 6.0 h) than in control DBA/2J (approximately 1.5 h) male mice. The stabilization of P450coh mRNA, therefore, is the primary mechanism for the induction by pyrazole of coumarin 7-hydroxylase. Phenobarbital, on the other hand, regulates the induction either translationally or posttranslationally. This drug affected neither the P450coh mRNA nor the P450coh gene's transcription levels in the DBA/2J male mice, although Western blots showed approximately a 3-fold increase of the P450coh protein in the liver microsomes of the drug-treated mice. The results indicate, therefore, that both phenobarbital and pyrazole regulate the P450coh induction posttranscriptionally; the former inducer enhances the translational efficiency of P450coh mRNA or alters the degradation rate of P450coh aproprotein, while the latter stabilizes P450coh mRNA. PMID- 1868079 TI - Effect of cobalamin derivatives on in vitro enzymatic DNA methylation: methylcobalamin can act as a methyl donor. AB - 5-Methylcytosine synthesis in DNA involves the transfer of methyl groups from S adenosyl-methionine to the 5'-position of cytosine through the action of DNA (cytosine-5)-methyltransferase. The rate of this reaction has been found to be enhanced by cobalt ions. We therefore analyzed the influence of vitamin B12 and related compounds containing cobalt on DNA methylation. Vitamin B12, methylcobalamin, and coenzyme B12 were found to enhance significantly the de novo DNA methylation in the presence of S-adenosylmethionine for concentrations up to 1 microM, but at higher concentrations these compounds were found to inhibit DNA methylation. Methylcobalamin behaves as a competitive inhibitor of the enzymatic methylation reaction (Ki = 15 microM), the Km for S-adenosylmethionine being 8 microM. In addition, the use of radioactive methylcobalamin shows that it can be used as a methyl donor in the de novo and maintenance DNA methylation reactions. Thus, two DNA methylation pathways could exist: one involving methylation from S adenosylmethionine and a second one involving methylation from methylcobalamin. PMID- 1868080 TI - Oligonucleotide site directed mutagenesis of all histidine residues within the T4 endonuclease V gene: role in enzyme-nontarget DNA binding. AB - In order to evaluate the contributions that histidine residues might play both in the catalytic activities of endonuclease V and in binding to nontarget DNA, the technique of oligonucleotide site directed mutagenesis was used to create mutations at each of the four histidine residues in the endonuclease V gene. Although none of the histidines were shown to be absolutely required for the pyrimidine dimer specific DNA glycosylase activity or the apurinic lyase activity, conservative amino acid changes at His16 produced enzymes with little or no catalytic activity. In addition, the evaluation of conservative and radical amino acid substitutions at positions 34, 56, and 107 is consistent with the interpretation that each of these histidines may be involved in nontarget DNA binding. The data supporting this conclusion are that histidine changes to lysine at positions 34 and 107 enhance the nontarget DNA binding activity of the mutant enzymes while neutralization of charge at His56 reduces nontarget DNA binding. PMID- 1868081 TI - Refolded HIV-1 tat protein protects both bulge and loop nucleotides in TAR RNA from ribonucleolytic cleavage. AB - Substantial evidence indicates that HIV-1 trans-activation by tat protein is mediated through the TAR RNA element. This RNA forms a stem-loop structure containing a three-nucleotide bulge and a six-nucleotide loop. Previous mutagenic analysis of TAR indicates that the bulge residues and a 4 bp segment of the stem constitute, in part, the tat binding site. However, there appears to be no sequence-specific contribution of the six-base loop. We have employed a ribonuclease protection technique to explore the interaction of tat with single stranded regions of TAR. The results indicate that tat interacts with both the bulge and loop regions of TAR. Treatment of TAR RNA with RNase A results in cleavage at U23 and U31, located in the bulge and loop regions, respectively. High concentrations (approximately 2 microM) of Escherichia coli derived tat protein, prepared by standard procedures, gave complete protection of TAR RNA from RNase A cleavage. However, under these conditions, truncated TAR derivatives in which no stem-loop structure is expected to form were also protected, indicating nonspecific binding. In order to obtain a tat preparation with enhanced specificity toward TAR RNA, methods were developed for refolding the recombinant protein. This treatment enhanced the affinity of tat for TAR by approximately 30-fold [Kd(apparent) less than 25 nM] and markedly increased its specificity for the TAR. Again, tat protected TAR RNA from RNase A cleavage at both U23 and U31. Protection was also observed with RNase T1 which cleaves TAR RNA at three G residues in the six-base loop.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868082 TI - The isolated C-terminal (F2) fragment of the Escherichia coli tryptophan synthase beta 2-subunit folds into a stable, organized nonnative conformation. AB - Proteolysis of the beta 2-subunit of Escherichia coli tryptophan synthase by the endoproteinase Glu C from Staphylococcus aureus V8 yields a peptide, F2, corresponding to the C-terminal 101 residues of the beta-chain. The conformation and stability of isolated F2 in phosphate buffer at pH 7.8 (where native beta 2 is stable) have been investigated. Circular dichroism spectra in the far-UV showed the presence of large amounts of secondary structure (19% alpha-helices, 34% extended beta-structures). Circular dichroism spectra in the near-UV and sedimentation velocity studies indicated an open globular structure with the aromatic side chains in a symmetric (or disordered) environment. NMR spectra and rates of amide proton exchange showed that F2 fluctuates rapidly between several conformations. The thermal denaturation of F2 observed by the loss of far-UV circular dichroism with increasing temperature appeared noncooperative, and indicates a high thermal stability (Tm = 70 degrees C). Differential scanning microcalorimetry confirmed the absence of cooperativity and indicated a very low value for the calorimetric enthalpy of denaturation (delta H = 17 kJ/mol). All these properties were compatible with a molten globule. However, the low sedimentation coefficient of F2 suggested a very hydrated and/or expanded structure, and the secondary structure content of isolated F2 (see above) differed widely from that reported in the literature for F2 within the context of native beta 2 (49% alpha-helices and 13% extended beta-structures). Thus, neither the secondary nor the tertiary structure of isolated F2 resembled those of native F2. In this respect, isolated F2 is not a "molten globule".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868083 TI - Multiplicity of acidic subunit isoforms of crotoxin, the phospholipase A2 neurotoxin from Crotalus durissus terrificus venom, results from posttranslational modifications. AB - Crotoxin, the major toxin of the venom of the South American rattlesnake, Crotalus durissus terrificus, is made of two subunits: component B, a basic and weakly toxic phospholipase A2, and component A, an acidic and nontoxic protein that enhances the lethal potency of component B. Crotoxin is a mixture of isoforms that results from the association of several isoforms of its two subunits. In the present investigation, we have purified four component A isoforms that, when associated with the same purified component B isoform, produced different crotoxin isoforms, all having the same specific enzymatic activity and the same lethal potency. We further determined by Edman degradation the polypeptide sequences of these four component A isoforms. They are made of three disulfide-linked polypeptide chains (alpha, beta, and gamma) that correspond to three different regions of a phospholipase A2 precursor. We observed that the polypeptide sequences of the various component A isoforms all agree with the sequence of an unique precursor. The differences between the isoforms result first by differences in the length of the various chains alpha and beta, indicating that component A isoforms are generated from the proteolytic cleavage of the component A precursor at very close sites, possibly by the combined actions of endopeptidases and exopeptidases, and second by the possible cyclization of the alpha-NH2 of the N-terminal glutamine residue of chains beta and gamma. These observations indicate that the component A isoforms are the consequence of different posttranslational events occurring on an unique precursor, rather than the expression of different genes. PMID- 1868084 TI - C-terminal structure and mobility of rabbit skeletal muscle light meromyosin as studied by one- and two-dimensional 1H NMR spectroscopy and X-ray small-angle scattering. AB - Intact rabbit myosin and two different C-terminal fragments of rabbit muscle light meromyosin (LMM) expressed in Escherichia coli, LMM-30, and LMM-30C', were studied by 1H NMR spectroscopy. X-ray small-angle scattering shows that at high ionic strength two polypeptide chains of LMM-30 (which consists of the C-terminal 262 amino acids of myosin heavy chain) or LMM-30C' (which corresponds to LMM-30 but lacks the last 17 residues) assemble to form an alpha-helical coiled-coil as it is found also in myosin. The last 12 C-terminal residues of one polypeptide chain of LMM-30 and the last 9 C-terminal residues of the other chain are very mobile. The last 8 residues of the two strands are equivalent from the NMR point of view and unfolded; the valine residues in position 255 in the two strands are not equivalent, suggesting an interaction between the two strands, Ser-252, Arg 253, and Asp-254 are completely immobilized in one of the polypeptide strands and partly mobile in the other. Essentially the same pattern is observed in intact myosin. In spite of the large molecular weights of LMM-30 and LMM-30C', it is possible to resolve almost all aromatic residues and to determine the pK values of all the 4 tyrosine and of 9 (out of 10) histidine residues. The tyrosine residues in the two strands are equivalent in the two polypeptide chains and both have a pK of 10.5. The pK values of the histidine residues vary between 5.7 and 7.0. PMID- 1868085 TI - The N-terminal domain of tissue inhibitor of metalloproteinases retains metalloproteinase inhibitory activity. AB - Recombinant tissue inhibitor of metalloproteinases (TIMP-1) and a truncated version containing only the three N-terminal loops, delta 127-184TIMP, have been expressed in myeloma cells and purified by affinity chromatography and gel filtration. delta 127-184TIMP was found to exist as two main glycosylation variants of molecular mass 24 kD and 19.5 kDa and an unglycosylated form of 13 kDa. All forms of the truncated inhibitor were able to inhibit and form complexes with active forms of the matrix metalloproteinases, indicating that the major structural features for specific interaction with these enzymes resides in these three loops. Stable binding of delta 127-184TIMP to pro 95-kDa gelatinase was not demonstrable under the conditions for binding of full-length TIMP-1. PMID- 1868086 TI - Isolation and amino acid sequence analysis of bovine adrenal 3 beta hydroxysteroid dehydrogenase/steroid isomerase. AB - 3 beta-Hydroxysteroid dehydrogenase/steroid isomerase has been purified to homogeneity from bovine adrenal glands. A single protein of molecular weight 42,090 +/- 40 containing both enzyme activities has been isolated. Approximately 86% of the amino acid sequence of the bovine adrenal 3 beta-hydroxysteroid dehydrogenase/steroid isomerase has been obtained by sequencing peptides isolated from digests with trypsin and lysyl endopeptidase and by chemical cleavage with CNBr. The sequence obtained is identical with that of the deduced amino acid sequence of the bovine ovarian 3 beta-hydroxysteroid dehydrogenase/steroid isomerase [Zhao et al. (1989) FEBS Lett. 259, 153-157], with the exception that the N-terminal methionine residue found in the bovine ovarian sequence is not present in the mature bovine adrenal enzyme. On the basis of the primary structure and comparisons with other NAD+ binding proteins, we propose a structural model of the bovine adrenal 3 beta-hydroxysteroid dehydrogenase/steroid isomerase localizing the NAD+ binding site as well as the membrane-anchoring segment. PMID- 1868087 TI - Affinity labeling of bovine adrenal 3 beta-hydroxysteroid dehydrogenase/steroid isomerase by 5'-[p-(fluorosulfonyl)benzoyl]adenosine. AB - Incubation of bovine adrenal 3 beta-hydroxysteroid dehydrogenase/steroid isomerase with 5'-[p-(fluorosulfonyl)benzoyl]adenosine (5'-FSBA) results in the inactivation of the 3 beta-hydroxysteroid dehydrogenase enzyme activity following pseudo-first-order kinetics. A double-reciprocal plot of 1/kobs versus 1/[5' FSBA] yields a straight line with a positive y intercept, indicative of reversible binding of the inhibitor prior to an irreversible inactivation reaction. The dissociation constant (Kd) for the initial reversible enzyme inhibitor complex is estimated at 0.533 mM, with k2 = 0.22 min-1. The irreversible inactivation could be prevented by the presence of NAD+ during the incubation, indicating that 5'-FSBA inactivates the 3 beta-hydroxysteroid dehydrogenase activity by reacting at the NAD+ binding site. Although the enzyme was inactivated by incubation with 5'-FSBA, no incorporation of the inhibitor was found in labeling studies using 5'-[p-(fluorosulfonyl)benzoyl] [14C]adenosine. However, the inactivation of 3 beta-hydroxysteroid dehydrogenase activity caused by incubation with 5'-FSBA could be completely reversed by the addition of dithiothreitol. This indicates the presence of at least two cysteine residues at or in the vicinity of the NAD+ binding site, which may form a disulfide bond catalyzed by the presence of 5'-FSBA. The intramolecular cysteine disulfide bridge was found between the cysteine residues in the peptides 274EWGFCLDSR282 and 18IICLLVEEK26, by comparing the [14C]iodoacetic acid labeling before and after recovering the enzyme activity upon the addition of dithiothreitol. PMID- 1868088 TI - Minimum requirements for protease activation of flavin pyruvate oxidase. AB - Previous investigations have shown that the catalytic efficiency (kcat/KM) of pyruvate oxidase can be enhanced 450-fold by chymotryptic cleavage of a 23 residue peptide (alpha-peptide) from the carboxy terminus of the enzyme. The minimum requirement for proteolytic activation has been investigated by exposing pyruvate oxidase to a variety of carboxypeptidases, either singly or in combination. The extent of carboxypeptidase hydrolysis was followed by analyzing the release of amino acids and by mass spectral analysis of the truncated alpha peptides which were derived from the carboxypeptidase-treated preparations. The results indicate that the removal of 7 carboxy-terminal residues does not activate the enzyme whereas the removal of 10 or 11 residues produces activated pyruvate oxidase. Activation of pyruvate oxidase by endoproteinase Glu-C confirms the carboxypeptidase results. Endoproteinase Glu-C specificity predicts hydrolytic cleavage of the peptide bond between Glu-561 and Val-562 with the removal of 11 residues from the carboxy terminus of the enzyme. PMID- 1868089 TI - Mechanism of inhibition of dopamine beta-monooxygenase by quinol and phenol derivatives, as determined by solvent and substrate deuterium isotope effects. AB - The mechanism of interaction of quinols and phenols with dopamine beta monooxygenase (D beta M) has been investigated. The ratio of quinone formation (from catechol) to oxygen consumption rises from a value of 1 in the presence of phenethylamine substrate to 2 in the absence of substrate. These results implicate quinol oxidation at both the reductant- and substrate-binding sites of D beta M. In the presence of saturating ascorbate, catechol and p-hydroquinol behave as mechanism-based inhibitors of D beta M, with partitioning ratios of turnover to inactivation of 21:1 and 41:1, respectively. Phenol is found to inactivate the enzyme in a manner similar to p-cresol, suggesting that the methyl group of p-cresol is not an essential component of enzyme inhibition. Solvent isotope effects on inactivation and turnover have been measured for various inactivators. Although the majority of these inhibitors, including catechol, p hydroquinol, aniline, phenethylenediamine, and benzylhydrazine, are characterized by relatively small solvent isotope effects (1.5-2.5) on the inactivation rate constant (ki), solvent isotope effects on ki for phenol and p-cresol are 5.7 and 7.4, respectively. By contrast, solvent isotope effects on the turnover of p cresol are almost unity. Using p-cresol-d7 as substrate, we observe D(kcat) = 5.2 and D(kcat/Km) = 3.1, while isotope effects on inactivation are D(ki) = 0.95 and D(ki/Ki) = 0.59. These results lead us to propose that inhibitors fall into two mechanistic classes, involving either one-electron oxidation to form radical cation intermediates (quinols) or hydrogen atom abstraction (phenols).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868090 TI - Investigation of an octapeptide inhibitor of Escherichia coli ribonucleotide reductase by transferred nuclear Overhauser effect spectroscopy. AB - Several peptides contained within the C-terminal sequence of the B2 subunit of Escherichia coli ribonucleotide reductase (RNR) were investigated for their ability to inhibit the enzyme, presumably by interfering with association of the B1 and B2 subunits. AcYLVGQIDSE, corresponding by sequence homology to a nonapeptide that inhibits herpes simplex RNR [Gaudreau et al. (1987) J. Biol. Chem. 262, 12413] shows no inhibition of the E. coli enzyme (IC50 greater than 3 mM), whereas AcDDLSNFQL, the C-terminal octapeptide of the E. coli B2 subunit, is a noncompetitive inhibitor (Ki = 160 microM). Neither bradykinin (RPPGFSPFR) nor the pentapeptide AcSNFQL inhibits the E. coli enzyme. Transferred nuclear Overhauser enhancement spectroscopy was used to probe the conformation of AcDDLSNFQL when it is bound to the B1 subunit. These experiments suggest that the peptide adopts a turn in the region of Asn5 and Phe6 and that a hydrophobic cluster of the phenylalanine and leucine side chains is involved in the interaction surface. PMID- 1868091 TI - Synthesis and evaluation of an inhibitor of carboxypeptidase A with a Ki value in the femtomolar range. AB - Comparative studies among a series of tripeptide phosphonate inhibitors of the zinc peptidase carboxypeptidase A indicate that incorporation of the phosphonic acid analogue of valine at the P1 position results in significantly higher affinity than the glycine, alanine, or phenylalanine analogues. When applied to the tripeptide analogue Cbz-Phe-ValP-(O)Phe [ZFVP(O)F], determination of the inhibition constant Ki was complicated by the very slow rate of dissociation. The rate of exchange of [3H]ZFVP(O)F with enzyme-bound [14C]ZFVP(O)F was followed for periods of 3-4 months to measure dissociation rate constants in the range of (1.7 4.4) x 10(-9) s-1, corresponding to half-lives of 5-13 years. Although the on- and off-rate constants differ for different carboxypeptidase isozymes, their ratios, corresponding to the inhibition constants Ki, are consistently in the range of 10-27 fM. Both the inhibition constants and the dissociation rate constants appear to be the lowest values yet determined for an enzyme-small inhibitor interaction. PMID- 1868092 TI - Comparison of the structures of three carboxypeptidase A-phosphonate complexes determined by X-ray crystallography. AB - The structures of the complexes of carboxypeptidase A (CPA) with two tight binding phosphonate inhibitors have been determined by X-ray crystallography. The inhibitors, Cbz-Phe-ValP-(O)-Phe[ZFVP(O)F] and Cbz-Ala-GlyP-(O)-Phe[ZAGP(O)F], bind noncovalently to CPA with dissociation constants (Ki's) of 11 fM and 710 pM, respectively. The CPA-ZFVP(O)F complex crystallizes in the space group P2(1)2(1)2(1) with unit cell parameters a = 65.3 A, b = 63.4 A, and c = 76.0 A, and the CPA-ZAGP(O)F complex crystallizes in the space group P2(1)2(1)2(1) with unit cell parameters a = 63.4 A, b = 65.9 A, and c = 74.4 A. Both structures were determined by molecular replacement to a resolution of 2.0 A. The final crystallographic residuals are 0.189 for the CPA-ZFVP(O)F complex and 0.191 for the CPA-ZAGP(O)F complex. The CPA-ZFVP(O)F complex exhibits the lowest Ki yet determined for an enzyme-inhibitor interaction. Comparison of the CPA-ZFVP(O)F structure with that of the CPA-ZAAP(O)F complex [Kim, H., & Lipscomb, W.N. (1990) Biochemistry 29, 5546-5555] indicates the likely important contributions of hydrophobic and weakly polar enzyme-inhibitor interactions to the exceptional stability of the CPA-ZFVP(O)F complex. Among these interactions is a network of four aromatic rings of CPA and ZFVP(O)F in a configuration that allows stabilizing aromatic-aromatic edge-to-face interactions from one ring to the next. A comparison of the structures of the CPA-ZFVP(O)F, CPA-ZAAP(O)F and CPA ZAGP(O)F complexes shows that all three phosphonates assume a similar binding mode in the active-site binding groove of CPA. For ZAGP(O)F, the glycyl P1 residue does not lead to an anomalous or a partially disordered binding mode as seen in some previous complexes of CPA involving dipeptide analogue inhibitors with glycyl P1 residues. The additional enzyme-inhibitor interactions for these tripeptide phosphonates secure a binding mode in which a Pi portion of the inhibitor is clearly bound by the corresponding Si binding subsite. These three phosphonates have been implicated as transition-state analogues of the CPA catalyzed reaction. The phosphinyl groups of these phosphonates coordinate to the active-site zinc in a manner that has been proposed as a characteristic feature of the general-base (Zn-hydroxyl or Zn-water) mechanism for the CPA-catalyzed reaction. Further mechanistic proposals are made for Arg-127, whose probable role in binding substrates is apparent in these CPA-phosphonate complexes. PMID- 1868093 TI - Electrochemical properties of the diiron core of uteroferrin and its anion complexes. AB - The reduction potentials (Em) of the purple acid phosphatase from porcine uterus, uteroferrin (Uf), and its phosphate, arsenate, and molybdate complexes were determined by coulometric methods at various pH values. The midpoint potential of Uf at the pH value for optimal enzyme activity (pH 5) was found to be +367 mV versus a normal hydrogen electrode (NHE), while at pH 6.01 Uf exhibits a reduction potential of +306 mV. At pH 6.01 molybdate was found to shift the potential of Uf more positive by 192 mV, while phosphate and arsenate shift the potential of Uf more negative by 193 and 89 mV, respectively. These shifts are consistent with the different susceptibilities of Uf to aerobic oxidation in the presence of these anions. Comparison of the reduction potential of Uf at pH 7.0 with those reported for other dinuclear non-heme iron enzymes and various (mu oxo)diiron model complexes suggest that the potential of Uf is too positive to be consistent with a mu-oxo-bridge in Ufo. The pH dependence of the reduction potentials of Uf (60 mV/pH unit) and the fact that the electron transfer rate increases with decreasing pH indicate a concomitant participation of a proton during the oxidation-reduction process. This process was assigned to the protonation of a terminally bound hydroxide ligand at the Fe(II) center upon reduction of Ufo. Structural implications provided by the electrochemical data indicate that molybdate affects the dinuclear core in a manner that differs from that of phosphate and arsenate. This observation is consistent with previous spectroscopic and biochemical studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868094 TI - Structural dynamics and functional domains of the fur protein. AB - Proteolytic enzymes were used to detect metal-induced conformational changes in the ferric uptake regulation (Fur) protein of Escherichia coli K12. Metal binding results in enhanced cleavage of the N-terminal region of Fur by trypsin and chymotrypsin. Activation of both trypsinolysis sensitivity and DNA binding have similar metal ion specificity and concentration dependencies, suggesting that the conformational change detected is required for operator DNA binding. Isolation and characterization of biochemically generated fragments of Fur as well as other data indicate that the N-terminal region is necessary for the interaction of the repressor with DNA and that a C-terminal domain is sufficient for binding to metal ions. PMID- 1868095 TI - Disposition of the phenylalanine B25 side chain during insulin-receptor and insulin-insulin interactions. AB - By the semisynthesis of both full-length insulin analogues and their des pentapeptide-(B26-B30)-alpha-carboxamide counterparts, we have examined the importance of the electronic character and bulk of the position B25 side chain both in directing insulin interaction with its receptor on isolated canine hepatocytes and in determining the ability of insulin to self-associate in solution. Analogues include those in which PheB25 was replaced by cyclohexyl-Ala; Tyr; p-nitro-, p-fluoro-, p-iodo-, or p-amino-Phe; or p-amino-Phe in which the aromatic amino function had been acylated by the acetyl, hexanoyl, decanoyl, or 1 adamantanoyl group. Our findings identify that (a) the beta-aromatic side chain at position B25 is indeed critical for high-affinity ligand-receptor interactions, (b) neither electron withdrawal from nor electron donation to the beta-aromatic ring perturbs ligand-receptor interactions in major ways, (c) considerable latitude is allowed the placement of linear or polycyclic apolar mass at the para position in p-amino-PheB25-substituted analogues with respect both to receptor binding affinity and to biological activity in vivo, and (d) para apolar mass at position B25 is readily accommodated during the self association of insulin monomers, as assessed by analytical tyrosine radioiodination and spectroscopic analysis of analogue complexes with Co2+ and Co3+. These findings are discussed in terms of a model for insulin-receptor interactions at the cell membrane in which the position B25 side chain defines the edge of intermolecular contact. PMID- 1868096 TI - Site-specific 1,N6-ethenoadenylated single-stranded oligonucleotides as structural probes for the T4 gene 32 protein-ssDNA complex. AB - Bacteriophage T4 gene 32 protein (g32P) is a DNA replication accessory protein that binds single-stranded (ss) nucleic acids nonspecifically, independent of nucleotide sequence. G32P contains 1 mol of Zn(II)/mol of protein monomer, which can be substituted with Co(II), with maintenance of the structure and activity of the molecule. The Co(II) is coordinated via approximately tetrahedral ligand symmetry by three Cys sulfur atoms and therefore exhibits intense S(-)----Co(II) ligand to metal charge-transfer (LMCT) transitions in the near ultraviolet [Giedroc, D. P., et al. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8452-8456]. A series of fluorescent 1,N6-ethenoadenosine (epsilon A)-containing oligonucleotides conforming to the structure (5'----3') d[(Tp)m epsilon A(pT)l-m 1] where 0 less than or equal to m less than or equal to l - 1 and length (l) six or eight nucleotides have been evaluated as dynamics probes and potential fluorescence energy transfer donors to Co(II) in mapping the spatial proximity of the (fixed) intrinsic metal ion and a variably positioned epsilon A-base in a series of protein-nucleic acid complexes. We provide spectroscopic evidence that the epsilon A-oligonucleotides bind to g32P-(A + B) with a fixed polarity of the phosphodiester chain. A Trp side chain(s) makes close approach to a epsilon A base positioned toward the 3' end of a bound l = 8 oligonucleotide. Six oligonucleotides of l = 8 and m = 0, 1, 3, 5, 6, or 7 were investigated as energy transfer donors to Co(II) at 0.1 M NaCl, pH 8.1, 25 degrees C upon binding to Co(II)-substituted or Zn(II) g32P-(A + B), i.e., in the presence and absence of an energy acceptor, respectively. Detectable quenching of the epsilon A fluorescence by the Co(II)-LMCT acceptors was found to occur in all epsilon A oligonucleotide-protein complexes, yielding energy transfer efficiencies (E) of 0.43, 0.31, 0.26, 0.26, 0.28, and 0.41 for l = 8 and m = 0, 1, 3, 5, 6, and 7 epsilon A-oligonucleotides, respectively. The two-dimensional distances R (in A) were found to vary as follows: d[epsilon A(pT)7] (m = 0), 16.0 (15.5-16.9); d[Tp epsilon A(pT)6] (m = 1), 17.7 (16.9-19.1); d[(Tp)3 epsilon A(pT)4] (m = 3), 20.7 (19.5-22.1); d[(Tp)5 epsilon A(pT)2] (m = 5), 20.5 (19.5-21.9); d[(Tp)6 epsilon ApT] (m = 6), 19.0 (18.0-20.4); and d[(Tp)7 epsilon A] (m = 7), 18.6 (17.8 19.8).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1868097 TI - Cell adhesion promoting peptide GVKGDKGNPGWPGAP from the collagen type IV triple helix: cis/trans proline-induced multiple 1H NMR conformations and evidence for a KG/PG multiple turn repeat motif in the all-trans proline state. AB - Peptide GVKGDKGNPGWPGAPY (called peptide IV-H1), derived from the protein sequence of human collagen type IV, triple-helix domain residues 1263-1277, represents an RGD-independent, cell-specific, adhesion, spreading, and motility promoting domain in type IV collagen. In this study, peptide IV-H1 has been investigated by 1H NMR (500 MHz) spectroscopy. Cis-trans proline isomerization at each of the three proline residues gives rise to a number of slowly exchanging (500-MHz NMR time scale) conformation states. At least five such states are observed, for example, for the well-resolved A14 beta H3 group, and K3, which is six residues sequentially removed from the nearest proline, i.e., P9, shows two sets. The presence of more than two sets of resonances for residues sequentially proximal to a proline, e.g., A14-cis-P15 and A14-trans-P15, and more than one set for a residue sequentially well-removed from a proline, e.g., K3, indicates long range conformation interactions and the presence of preferred structure in this short linear peptide. Many resonances belonging to these multiple species have been assigned by using mono-proline-substituted analogues. Conformational (isomer) state-specific 2D 1H NMR assignments for the combination of cis and trans proline states have been made via analysis of COSY-type, HOHAHA, and NOESY spectra. Peptide IV-H1 in the all-trans proline state ttt exists in relatively well-defined conformation populations showing numerous short- and long-range NOEs and long-lived backbone amide protons and reduced backbone NH temperature coefficients, suggesting hydrogen-bonding, and structurally informative 3J alpha N coupling constants. The NMR data indicate significant beta-turn populations centered at K3-G4, K5-G6, P9-G10, and P12-G13, and a C-terminal gamma-turn within the A14-P15-Y16 sequence. These NMR data are supported by circular dichroic studies which indicate the presence of 52% beta-turn, 10% helix, and 38% random coil structural populations. Since equally spaced KG and PG residues are found on both sides of peptide IV-H1 in the native collagen type IV sequence, this multiple turn repeat motif may continue through a longer segment of the protein. Synthetic peptide IV-H1 overlapping sequence "walk throughs" indicate that the primary biological activity is localized in the GNPGWPGAP double beta-turn domain, which contains the backbone constraining proline residues. This proline domain conformation may suggest a collagen type IV receptor-specific, metastatic cell adhesion promoting binding domain. PMID- 1868098 TI - Interaction of lipid vesicles with monomolecular layers containing lung surfactant proteins SP-B or SP-C. AB - Pulmonary surfactant contains two families of hydrophobic proteins, SP-B and SP C. Both proteins are thought to promote the formation of the phospholipid monolayer at the air-fluid interface of the lung. The Wilhelmy plate method was used to study the involvement of SP-B and SP-C in the formation of phospholipid monolayers. The proteins were either present in the phospholipid vesicles which were injected into the subphase or included in a preformed phospholipid monolayer. In agreement with earlier investigators, we found that SP-B and SP-C, present in phospholipid vesicles, were able to induce the formation of a monolayer, as became apparent by an increase in surface pressure. However, when the proteins were present in a preformed phospholipid monolayer (20 mN/m) at similar lipid to protein ratios, the rate of surface pressure increase after injection of pure phospholipid vesicles into the subphase at similar vesicle concentrations was 10 times higher. The process of phospholipid insertion from phospholipid vesicles into the protein-containing monolayers was dependent on (1) the presence of (divalent) cations, (2) the phospholipid concentration in the subphase, (3) the size of the phospholipid vesicles, (4) the protein concentration in the preformed monolayer, and (5) the initial surface pressure at which the monolayers were formed. Both in vesicles and in preformed monolayers, SP-C was less active than SP-B in promoting the formation of a phospholipid monolayer. The use of preformed monolayers containing controlled protein concentrations may allow more detailed studies on the mechanism by which the proteins enhance phospholipid monolayer formation from vesicles. PMID- 1868099 TI - Localization of regions of the Torpedo californica nicotinic acetylcholine receptor labeled with an aryl azide derivative of phosphatidylserine. AB - A photoactivatable analog of phosphatidylserine, 125I-labeled 4-azidosalicylic acid-phosphatidylserine (125I-ASA-PS) (Blanton, M. and Wang, H.H. (1990) Biochemistry 29, 1186-1194) was used to label the nicotinic acetylcholine receptor. The photoactivatable group of 125I-ASA-PS is attached directly to the phospholipid head group making it an excellent probe of regions of the AchR structure in contact with the negatively-charged head group of phosphatidylserine. The 'binding domains' were localized by chemically cleaving the labeled receptor with cyanogen bromide (CNBr), separating the generated peptides by reverse-phase HPLC, and N-terminal sequence analysis of radiolabeled material. CNBr fragments containing flanking regions of the transmembrane spanning region M4 as well as within M3 were identified within HPLC separated radiolabeled material. The results suggest a topological arrangement of the transmembrane helices in which the hydrophobic faces of M3 and M4 form the boundary of the receptor complex in contact with the lipid bilayer. PMID- 1868100 TI - The influence of acyl chain-length asymmetry on the phase transition parameters of phosphatidylcholine dispersions. AB - The influence of acyl chain-length asymmetry on the thermodynamic parameters (Tm, delta H, and delta S) associated with the reversible main phase transition of aqueous dispersions prepared from saturated diacyl phosphatidylcholines was studied by high-resolution differential scanning calorimetry. Two series of saturated diacyl phosphatidylcholines, grouped according to their molecular weights of 678 and 706, with a total number of 25 molecular species were examined. The normalized acyl chain-length difference between the sn-1 and sn-2 acyl chains for a given phospholipid molecule in the gel-state bilayer is expressed quantitatively by the structural parameter delta C/CL, and the values of delta C/CL for the two series of lipids under study vary considerably from 0.04 to 0.67. When the value of delta C/CL is within the range of 0.09-0.40, it was shown that the thermodynamic parameters are, to a first approximation, a linear function of delta C/CL with a negative slope. In addition, the experimental Tm values and the predicted Tm values put forward by Huang (Biochemistry (1991) 30, 26-30) are in very good agreement. Beyond the point of delta C/CL = 0.41, the influence of acyl chain-length asymmetry on the thermodynamic parameters deviates significantly from a linear function. In fact, within the range of delta C/CL values of 0.42-0.67, the thermodynamic parameters in the Tm (or delta H) vs. delta C/CL plot were shown to be bell-shaped with the maximal Tm (or delta H) at delta C/CL = 0.57. These results are discussed in terms of changes in the acyl chain packing modes of various phosphatidylcholine molecules within the gel-state bilayer in excess water. PMID- 1868101 TI - Evidence for net uptake and efflux of mitochondrial coenzyme A. AB - Coenzyme A transport was studied by determining [14C]CoA associated with isolated rat heart mitochondria. HPLC analysis of a mitochondrial extract obtained following incubation with [14C] CoA revealed an increase in [14C] CoA. In the presence of pyruvate or alpha-ketoglutarate, [14C]CoA associated with mitochondria was converted to acetyl- or succinyl-[14C]CoA, respectively, demonstrating the intramitochondrial localization of transported CoA. Net uptake of CoA was demonstrated by the findings that the increase in mitochondrial content of CoA following incubation with CoA was equal to the values of CoA uptake obtained from experiments using [14C]CoA. Sequestration of intramitochondrial CoA as metabolically inert derivatives with maleate stimulated CoA uptake, supporting the concept of unidirectional CoA uptake rather than exchange. Altering the membrane electrochemical gradient with valinomycin, nigericin, calcium, phosphate or a combination of phosphate and calcium caused efflux of endogenous CoA. The largest efflux was observed with valinomycin or a combination of Ca2+ and Pi. The Ca2+ and Pi-induced CoA efflux was effectively prevented by succinate or pyruvate. The results suggest that the uptake process, which is dependent on the membrane electrical gradient can be reversed by dissipating the electrical gradient. The relevance of CoA efflux induced by Ca2+ and Pi is discussed with respect to reperfusion injury following ischemic damage. Other factors regulating the maintenance of CoA within the mitochondrial matrix include the matrix pH and the acylation state of CoA. PMID- 1868102 TI - Reconstitution and partial purification of an amiloride-sensitive, cation channel from rabbit kidney. AB - The aim of the present study was to reconstitute and purify an epithelial potassium channel from rabbit kidney. Renal brush border membrane vesicles (BBMV) were found to contain a potassium conductance which was inhibited by amiloride, 5 (N-methyl-N-isobutyl)amiloride (MIA) and by barium. Membrane vesicle proteins were solubilized and reconstituted in proteoliposomes. Channel activity was assayed using Acridine orange and the voltage sensitive dye, 3,3' diethylthiadicarbocyanine iodide (DiSC2(5)). Both methods yielded similar results which indicated the presence of an amiloride-sensitive, cation channel in the proteoliposomes. This channel was more permeable to K than to Na and its activity was increased in reconstituted proteoliposomes as compared to native brush border membranes. We conclude that rabbit BBMV possess an amiloride sensitive cation channel. Channel activity was successfully reconstituted in proteoliposomes and the protein was partially purified during reconstitution. PMID- 1868103 TI - The Hofmeister effect in relation to membrane lipid phase stability. AB - The phase behaviour of L-alpha-1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) was examined in aqueous dispersions containing a range of sodium salts. The phase properties of the lipid exhibited a graded response to the presence of simple anions analogous to that of the Hofmeister series encountered in the study of the solution properties of proteins. Salts early in the series (such as Na2SO4 and NaCl) gave rise to substantial decreases in the temperature (Th) of the transition from the lamellar liquid-crystal to inverted hexagonal phase (L alpha- --HII) and small increases in the temperature (Tm) of the transition from the lamellar gel to lamellar liquid-crystal phase (L beta----L alpha). Salts towards the end of this series (such as NaI and NaSCN) led to increases in Th and decreases in Tm. Similar effects were seen in lipid dispersions containing a series of non-ionic co-solutes. In both cases, the relative efficiency of perturbation of the lipid phase properties reflected the relative ability of the anion or co-solute to influence the structure of the bulk water. X-ray diffraction measurements indicated that these effects were probably mediated through the ability of the co-solutes to bring about changes in the extent of the lipid/water interface. PMID- 1868104 TI - Visualization of exocytotic secretory processes of mast cells by fluorescence techniques. AB - Secretory processes via exocytosis in rat peritoneal mast cells were visualized by two complementary fluorescence techniques; one staining pre-exocytotic granules with a basic probe and the other staining post-exocytotic granules with acidic probes. Granules within mast cells were selectively stained with acridine orange and emitted orange yellow fluorescence. Upon stimulation with compound 48/80, release of acridine orange from granules was observed both in population and single cell measurements. This release was seen in some localized area of mast cells. Opening of pores between plasma membranes and granule membranes was monitored using acidic fluorescence probes such as 6-carboxyfluorescein or lucifer yellow CH. Not only granules located at peripheral region, but also granules near the core region participated in exocytosis. The existence of junctions between these granules was suggested. TMA-DPH, a lipophilic membrane probe, which was localized at plasma membrane before stimulation, diffused into granule membranes after stimulation. This shows that after stimulation, some constituents of plasma and granule membranes were mixed. Even after extensive degranulation, mast cells extruded acidic probes, indicating the plasma membranes still play a role of barrier. Activation of lateral motion of granules preceding to exocytosis was not observed. It was concluded that the visualization of secretory processes by fluorescence and image processing techniques will be useful for the study of molecular mechanisms underlying exocytosis. PMID- 1868105 TI - Net phosphate transport in phosphate-starved Candida utilis: relationships with pH and K+. AB - Phosphate transport was studied in phosphate-starved Candida utilis using 31P-NMR and in situ pH and K(+)-specific electrodes. A transient efflux of K+ was associated with the initial net influx of orthophosphate across the plasma membrane and decrease of both the plasma membrane pH gradient and the cytosol pH. Recovery of cytosol pH, and the plasma membrane pH gradient after phosphate uptake, was slow when extracellular K+ was depleted, but rapid when K+ was added to the suspension either with orthophosphate or after phosphate uptake. Net phosphate transport into the vacuole occurs against its concentration gradient and is associated with an increase of the tonoplast pH gradient. It is proposed that transport of orthophosphate into the vacuole is mediated by an electrical uniport and driven by the tonoplast membrane potential. PMID- 1868106 TI - Affinity-chromatographic purification of sixteen cysteine-substituted maltoporin variants: thiol reactivity and cross-linking in an outer membrane protein of Escherichia coli. AB - Wild-type and 16 variant maltoporins with site-directed cysteine substitutions at 14 sites were purified by a novel one-step affinity-chromatographic procedure. The trimer stability of purified proteins with C22S, C38S and G103C substitutions was reduced compared to wild-type maltoporin. Quantitative labelling with N ethyl[14C]maleimide, cross-linking with bifunctional bismaleimides and disulphide formation was used to test the reactivity of cysteines in the folded protein. The maleimide reactivity of the residues was in the order: 152 approximately equal to 153 greater than 265 greater than 30 approximately equal to 103 approximately equal to 120 approximately equal to 154 approximately equal to 382 greater than 57 approximately equal to 146, with the other sites (22, 38, 97, 184) poorly labelled. Only cysteines at 152 or 153 permitted the formation of inter-subunit disulphide bonds suggesting these residues are located within 0.5-0.9 nm of each other in homotrimers of maltoporin. S152C and S153C as well as S154C permitted the formation of inter-subunit cross-links using bifunctional bismaleimides. The cross-linkability and the high reactivity to N-ethylmaleimide of the 150 region was consistent with the current model of the structure of maltoporin in the outer membrane; the reactivity of the other sites is also discussed within the context of this model. PMID- 1868107 TI - Studies on the anion binding selectivity of sarcoplasmic reticulum membranes by 35Cl-NMR. AB - Anion binding sites on the membranes of sarcoplasmic reticulum vesicles can be characterized with the aid of 35Cl-NMR. Titration experiments with a series of different anions reveal that multivalent, phosphate-like anions bind much stronger to SR vesicles than monovalent anions like halides whereas oxalate seems to have an intermediate position. The binding strength decreases with decreasing ionic radius according to the following sequence: vanadate greater than phosphate greater than sulfate much greater than iodide greater than oxalate greater than bromide greater than chloride much greater than fluoride. This is also reflected by increasing dissociation constants. Although vanadate in absolute terms replaces much more chloride than either, phosphate or sulfate, their dissociation constants are very similar. This implicates a special binding mechanism for vanadate. Phosphate analoguous compounds like pyridoxalphosphate-6-azophenyl-2' sulfonic acid and its 4'-nitroderivative show the strongest binding. PMID- 1868108 TI - Post-acute management of head injuries. AB - Many advances have been made in the last 15 years in the treatment of traumatic brain injuries. This paper reviews the advances not only in the acute management stage but also in the crucial rehabilitation phases, both acute and post-acute. Rehabilitation of the brain-injured patient has been shown to result from therapies rather than spontaneous improvement and take years to accomplish, emphasizing the need for a coordinated continuum of rehabilitation programs. There is now evidence that coma and vegetative states are sometimes reversible with a combination of treatments, among them neuropharmacology. PMID- 1868109 TI - First single lung transplant in Virginia. AB - Lung transplantation is now established as a clinical reality for patients with irreversible, lethal pulmonary conditions. We report the first successful application of this treatment modality in Virginia. PMID- 1868110 TI - Alcohol abuse among college freshmen in Greek societies. PMID- 1868111 TI - Role of colonoscopy in treatment of colorectal carcinoma. PMID- 1868112 TI - Conjugation of phenyl isothiocyanate derivatives of carborane to antitumor antibody and in vivo localization of conjugates in nude mice. AB - A systematic study of the conjugation of 1-(p-isothiocyanatophenyl)-1,2-dicarba closo-[2-3H]dodeca borane(12), 3H-1, and 7-(p-isothiocyanatophenyl)dodecahydro 7,8-dicarba-nido -[8-3H] undecaborate(1-)ion, 3H-2, to the murine monoclonal anti CSAp antibody, Mu-9, was carried out to compare charged and uncharged boron cages in their effect upon antibody loading. Approximately one neutral cage and four of the anionic cages were successfully linked to antibody in two separate conjugates which were subsequently radioiodinated and evaluated in vivo. No significant loss of the antibody or its immunoreactivity was observed in either case. In nude mice bearing GW-39 tumor xenografts the conjugate containing the anionic carborane derivative showed a reduced tumor uptake although the tumor:non-tumor ratio was similar to that of the native antibody. The carborane cage in 2 was radiolabeled with 125I followed by attempts to purify and conjugate product 4 to a model goat IgG protein. This exploratory conjugation study was undertaken as a prelude to linking new conjugation reagents, which contain multiple anionic boron cages, to antitumor antibodies. The latter conjugates are required to maximize boron loading for the purpose of neutron-capture therapy. PMID- 1868113 TI - Radioiodinated iodobenzoyl conjugates of a monoclonal antibody Fab fragment. In vivo comparisons with chloramine-T-labeled Fab. AB - A comparative investigation of the biodistributions of radioiodinated p- and m iodobenzoyl conjugates of a monoclonal antibody Fab fragment, NR-LU-10 Fab, and the same antibody Fab fragment radioiodinated by the chloramine-T (ChT) method has been carried out in mice. Coinjected, dual-isotope studies in athymic mice with tumor xenografts have demonstrated that there are only minor differences in the in vivo distributions of the iodobenzoyl-labeled Fabs, except in the excretory organs, kidneys, and intestines, where major differences were observed. Similarly, coinjection of either the p-iodobenzoyl or m-iodobenzoyl conjugate of NR-LU-10 Fab with the Fab radioiodinated with ChT/radioiodide into BALB/c mice provided additional data that indicated that the two iodobenzoyl conjugates distributed similar in a number of selected tissues. The tissue-distribution differences of the regioisomeric iodobenzoyl conjugates in relation to the ChT radioiodinated Fab were large for the stomach and neck, consistent with previous studies. The most notable difference between the two iodobenzoyl conjugates was the kidney activity, where the m-iodobenzoyl conjugate was similar to the directly labeled Fab, but the p-iodobenzoyl-conjugated Fab was higher by nearly a factor of 2. PMID- 1868114 TI - Synthesis and characterization of protein and polylysine conjugates of sulfamethoxazole and sulfanilic acid for investigation of sulfonamide drug allergy. AB - Conjugates of sulfamethoxazole (SMX) with human serum albumin (HSA), transferrin (TR), and poly(L-lysine) (PL, degrees of polymerization 16 and 430) have been prepared. As a model, succinylSMX-glycine methyl ester was synthesized by carbodiimide and active ester routes. The proteins and PL were acylated with succinylSMX succinimido ester, affording conjugates (succinylSMX)2-21-HSA, (succinylSMX)17,27-TR, (succinylSMX)11-Lys16, and (succinylSMX)71-Lys430 in which SMX was linked by a spacer chain of four carbons. This represents substitution of up to 35, 46, 65, and 17% of the amino groups of HSA, TR, PL16, and PL430, respectively. HSA was also acylated with the succinimido esters of succinylSMX glycine and succinylSMX-epsilon-aminohexanoic acid, affording conjugates (succinylSMX-Gly)53-HSA and (succinylSMX-epsilon-NH2hex)51-HSA. In these conjugates SMX was linked by a spacer chain of 7 and 11 carbons, respectively, and almost all the amino groups of HSA were substituted. Factors apparently influencing the extent of conjugation to HSA were the stability of the active ester and the solubility of the conjugation reaction mixture. A sulfanilic acid (SA) conjugate, containing 12 mol of ligand/mol of HSA, was also prepared. The route of synthesis involved acylation of HSA with sulfanilyl fluoride. N-epsilon Sulfanilyl-L-lysine dihydrochloride, required for quantitation of bound SA, was synthesized by a new route starting from alpha-Boc-L-lysine. Conjugates (sulfanilyl)12-HSA and (succinylSMX)13-HSA, differing in molecular weight from HSA by only 2.6 and 6.5%, were distinguishable from HSA by gel-filtration HPLC, as were the more highly substituted conjugates from their respective unsubstituted materials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868115 TI - A novel bifunctional metabolizable linker for the conjugation of antibodies with radionuclides. AB - A novel heterogeneous bifunctional reagent containing an ester bond, N-[[4-(2 maleimidoethoxy)-succinyl]oxy]succinimide (MESS), was designed and synthesized for the conjugation of antibodies with the gallium-67 (67Ga) chelate of succinyldeferoxamine (SDF) via the ester bond. MESS was synthesized by the acylation of N-(2-hydroxyethyl)maleimide with succinic anhydride, followed by the activation of the resulting carboxylic acid to a succinimido ester. MESS possesses a maleimide group for protein conjugation and an active ester group for deferoxamine (DFO) coupling, and the two functional groups are linked via ester bonding. Conjugation of 67Ga-SDF with nonspecific human IgG was performed by reacting freshly thiolated IgG with the reaction product of MESS and DFO, followed by 67Ga labeling of the resulting conjugate using GaCl3 (67Ga-DFO-MESS IgG). For comparison, 67Ga-DFO conjugated nonspecific human IgG with a nonmetabolizable linkage was synthesized under the same conjugation conditions as those for 67Ga-DFO-MESS-IgG, using a nonmetabolizable heterogenous bifunctional reagent [N-[(6-maleimidocaproyl)oxy]succinimide, EMCS] instead of MESS (67Ga-DFO EMCS-IgG). HPLC size-exclusion chromatography of both preparations showed a single radioactivity and UV peak corresponding to the intact IgG. Generation of 67Ga-SDF from the 67Ga-DFO-MESS-IgG was demonstrated by reverse-phase HPLC analysis and cellulose acetate electrophoresis after the incubation of 67Ga-DFO MESS-IgG in a buffered solution containing carboxyesterase. After injection of 67Ga-DFO-MESS-IgG into mice, faster radioactivity clearance from the blood and less radioactivity accumulation in the liver, kidney, and spleen was noted than when 67Ga-DFO-EMCS-IgG was injected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868117 TI - Analysis of an experimental cortical network: I). Architectonics of visual areas 17 and 18 after neonatal injections of ibotenic acid; similarities with human microgyria. AB - Lesions of cortical areas 17 and 18 have been produced in newborn kittens by local injections of the excitotoxin ibotenic acid (ibo). Twenty-four hours after an injection on postnatal days 2 or 3, the gray matter of areas 17 and 18 near the center of the injection appears completely destroyed, with the exception of a one-to-two cell-thick layer at the bottom of layer I. Intact migrating neurons and radial glia can be found light- and electron-microscopically in the region affected. During the following weeks a several hundred micron thick cortex reforms. In the adult, this cortex consists of superficial layers I, II and III as proven by cytoarchitectonics, continuity with the corresponding layers of the normal cortex and cellular composition. We believe that the recovery is due to completion of migration by neurons spared by the ibo injection. More severe destruction of cerebral cortex, i.e. complete loss of the neuronal layers or their reduction to a few cell-thick mantles can be obtained with ibo injections at the end of the second or, respectively, first postnatal week. Severity of lesion also depends on the dose of ibo injected. There are interesting similarities between the ibo-injured cortex and two human neocortical displasias: microgyria and ulegyria. PMID- 1868116 TI - Trifunctional agents as a design strategy for tailoring ligand properties: irreversible inhibitors of A1 adenosine receptors. AB - The 1,3-phenylene diisothiocyanate conjugate of XAC (8-[4-[[[[(2 aminoethyl)amino]carbonyl]methyl]- oxy]phenyl]-1,3-dipropylxanthine, a potent A1 selective adenosine antagonist) has been characterized as an irreversible inhibitor of A1 adenosine receptors. To further extend this work, a series of analogues were prepared containing a third substituent in the phenyl isothiocyanate ring, incorporated to modify the physiochemical or spectroscopic properties of the conjugate. Symmetrical trifunctional cross-linking reagents bearing two isothiocyanate groups were prepared as general intermediates for cross-linking functionalized congeners and receptors. Xanthine isothiocyanate derivatives containing hydrophilic, fluorescent, or reactive substituents, linked via an amide, thiourea, or methylene group in the 5-position, were synthesized and found to be irreversible inhibitors of A1 adenosine receptors. The effects of the 5-substituent on water solubility and on the A1/A2 selectivity ratio derived from binding assays in rat brain membranes were examined. Inhibition of binding of [3H]-N6-(2-phenylisopropyl)-adenosine and [3H] CGS21680 (2-[2-[4 carboxyethyl)phenyl]ethyl]amino] adenosine-5'-N-ethylcarboxamide) at central A1 and A2 adenosine receptors, respectively, was measured. A conjugate of XAC and 1,3,5-triisothiocyanatobenzene was 894-fold selective for A1 receptors. Reporter groups, such as fluorescent dyes and a spin-label, were included as chain substituents in the irreversible binding analogues, which were designed for spectroscopic assays, histochemical characterization, and biochemical characterization of the receptor protein. PMID- 1868118 TI - Photoreceptor cell rescue at early and late RPE-cell transplantation periods during retinal disease in RCS dystrophic rats. AB - Normal retinal pigment epithelial (RPE) cells were transplanted into retinas of Royal College of Surgeons (RCS) dystrophic rats at different stages of the retinal disease process. RPE-cell transplantation at 10, 17 and 26 days resulted in rescue of photoreceptor cells, such that at 4 months the outer nuclear layer (ONL) was 8-10 cells in thickness as shown in retinas of age-matched control rats. Of these transplantation times, day 17 appeared to affect the best rescue of photoreceptor cells. Nongrafted retinas of 4 month-old RCS dystrophic rats exhibited scattered PRC's, most prevalent in the peripheral retina. In addition, a small, but significant increase in the ONL thickness was detected in vehicle injected retinas (sham control) of 17 day-old RCS dystrophic rats at 2 months; however, at 3 months, the ONL thickness was reduced to control levels. A normal distribution of (Na+ + K+)-ATPase immunostain was demonstrated beneath grafted RPE cells in retinas of 4 month-old RCS dystrophic rats. Dense immunostaining was shown along rescued photoreceptor cell inner segments (IS), within the inner (IPL) and outer (OPL) plexiform layers and on plasmalemma of cell bodies in the inner nuclear layer (INL). In nongrafted retinas of age-matched RCS dystrophic rats, immunostaining for (Na+ + K+)-ATPase was observed only in the INL and IPL. Under RPE-cells transplants in retinas of 4 month-old RCS dystrophic rats, opsin immunostaining was detected along both rescued photoreceptor cell inner and outer (OS) segments and on plasmalemma of ONL cell bodies. However, immunostaining for opsin was restricted to a debris zone in nongrafted retinas of age-matched RCS dystrophic rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868119 TI - Fetal transplant-induced restoration of spatial memory in rats with lesions of the nucleus basalis of Meynert. AB - Bilateral lesions of the nucleus basalis of Meynert (nbM) in rats produced mnemonic deficits when subjects were tested on tests of spatial memory over a period of 3 to 7.5 months postoperatively. The transplantation of cholinergic rich, fetal ventral forebrain tissue to either two or four frontoparietal cortical sites normalized performance on the spatial memory tasks. However, which transplant condition yielded recovery depended upon the nature of the task and/or posttransplantation interval. When assessed 8 months following transplant surgery, cortical choline acetyltransferase and acetylcholinesterase activity levels in both transplant groups were comparable to those values found in sham operated animals. These data indicate that fetal transplants can reverse the mnemonic deficits and restore cortical cholinergic neurochemical activity to near normal levels in rats with nbM lesions. PMID- 1868120 TI - Continuing education. PMID- 1868121 TI - Enhancing self-care of the elderly client: practical teaching tips for ostomy care. PMID- 1868122 TI - A survey of patient perception of quality of care. PMID- 1868123 TI - Reflections upon the history and future of the IAET. PMID- 1868124 TI - A proposal for a new classification of skin barriers. PMID- 1868125 TI - Urinary incontinence. PMID- 1868126 TI - In vivo models in the study of osteopenias. AB - A better insight into bone pathophysiology is required for a full understanding of the mechanisms leading to bone loss in humans. Animal models of bone disease appear to be the most valuable for this purpose. Certain differences in bone metabolism exist between various species. Non-human primates are the most human compatible animal species, whereas dogs appear to be most appropriate among small laboratory animals. However, the high cost of studies on primates and dogs restricts the number of animals examined. The rat is the most frequently used animal. Many similarities have been observed in bone metabolism of humans and rats. Like humans, rats also lose bone with aging, and in some parts of the rat skeleton bone remodelling occurs. However, bone metabolism in rat is mainly characterized by growth and modelling, which makes the rat model completely appropriate for studies of juvenile osteopenias. Characteristics of animal models of osteopenias should be comprehensively investigated in order to render the study results completely, or with known exceptions, comparable to the corresponding processes in humans. PMID- 1868127 TI - Reference methods as a basis for accurate measuring systems. AB - Reference methods, as part of a reference system, are essential for improving the accuracy of routine methods. They can help to establish worldwide compatibility of clinical chemical measurements and they provide an objective basis for quality control measures. The subject of analytical errors is treated in detail, then the concept of reference methods is developed. This review emphasizes the fundamental metrological aspects of reference methods and reference measurement technology. An overview is given of the most important analytical principles used for reference methods in clinical chemistry. The particular problems of reference methods for the determination of the catalytic activity concentration of enzymes are outside the scope of this review. PMID- 1868128 TI - The development of reference methods in clinical chemistry. The contribution of the Community Bureau of Reference of the Commission of the European Communities. AB - The use of reference method procedures in clinical chemical analysis is advocated by many experts as the most reliable approach to obtaining accurate results. The performance of such procedures must, however, be rigorous. This contribution will emphasize the importance of interlaboratory studies for this purpose. Examples will be presented, taken from the work done under the BCR programme of the Commission of the European Communities. The determination of steroid hormones in serum by isotope dilution mass spectrometry and the measurement of enzyme catalytic activities, according to IFCC recommended methods, will be discussed. PMID- 1868129 TI - Reference materials--a main element in a coherent reference measurement system. AB - The analytical reliability of any measurement procedure requires a specifically designed, coherent reference measurement system, including interrelated measurement procedures and measurement standards such as reference materials. The latter may be characterized by three sets of characteristics. The general characteristics comprise origin, mode of production, physical state and phase, homogeneity, physical form, container, additives, storage conditions, stability, and dangerous properties. The specific characteristics describe molecular composition, analyte, purity, matrix, quantity of interest (including scale), assigned value, and uncertainty of measurement. The additional characteristics concern the way in which values for other characteristics were obtained, the hierarchical position of the material, certificate, instructions for use, and intended function. The problem areas of reference materials comprise definition of the appropriate analyte, purification, matrix, assignment of values, and nomenclature. The present ambiguous terminology is presented and a systematic structure of descriptive names is proposed (tab. 1). PMID- 1868130 TI - Reference materials. AB - This paper summarizes the practical experience gained in the Federal Republic of Germany in connection with the development and implementation of a national reference system. The National Reference System is set forth in: 1. the New Calibration Act 1986 (Neufassung des Eichgesetzes vom 22. Februar 1985. Bundesgesetzblatt 1985, Teil I, 410-422); 2. the New Weights and Measures Regulations 1988 (Eichordnung vom 12. August 1988. Bundesgesetzblatt 1988, Teil I, 1657-1674). 3. the Guidelines of the Federal Medical Association (1988) for Quality Assurance in Medical Laboratories (Richtlinien der Bundesarztekammer zur Qualitatssicherung in medizinischen Laboratorien vom 16. Januar und 16. Oktober 1987. Deutsches Arzteblatt 85 (11) (1988), A-699--A-712). PMID- 1868131 TI - IFCC reference methods for measurement of pH, gases and electrolytes in blood: reference materials. AB - The Scientific Division Committee on pH, Blood Gases and Electrolytes of the International Federation of Clinical Chemistry (IFCC) produced recommendations to attempt to make the results of pH, blood gas and electrolyte analysis from different clinical chemistry laboratories internationally compatible. The aim of this lecture is to discuss the essential aspects of 1. the IFCC approved (1986) reference method for pH measurement in blood, 2. the IFCC approved (1988) reference method for tonometry of blood, 3. the provisionally proposed recommendations on the expression of results obtained with ion-selective electrodes for measuring sodium, potassium and calcium in serum, plasma or blood and 4. the reference method for the determination of ionized calcium in serum, plasma or blood. Also reference materials for quality control of pH, blood gas and electrolyte measurements are reviewed. Failures of several types of currently available quality control materials are discussed. PMID- 1868132 TI - Reference methods for the determination of sodium, potassium, pH and blood gases with ion-selective electrodes. AB - The determination of sodium and potassium in serum will be performed in the near future mainly by ion-selective electrodes. When the samples are highly diluted before measurement, a demonstrably accurate value of the electrolyte concentration in serum can be obtained. Accuracy control by using the pertinent reference methods of the National Institute of Standards and Technology (NIST) is well established for this purpose. In undiluted samples a potential is measured by ion-selective electrodes, which is dependent on the relative molal activity of the electrolyte, from which free molal concentration can be estimated. Usually, the total molal concentration of e.g. sodium is about 1.5% higher than that of free sodium, as it includes portions bound to e.g. carbonate and proteins. Accuracy control is hampered, because reference methods for either relative molal activity or free molal concentration are not yet available. Reference method values for total molal concentration will differ systematically from an accurate value for free molal concentration. When ion-selective electrodes are calibrated by using "normal" sera, accuracy control can be based on the reference method of the NIST; but this is valid only for a very narrow, at best "normal", concentration range of proteins and lipids, assuming, of course, that binding is normal. The greater the variation of the concentration of macromolecules from normal (lower or higher), the greater the difference between the values obtained by the two methods. Calibration of ion-selective electrodes by using sera (this is the least desirable approach for calibration) requires the introduction of a new unit of measurement, which is not compatible with the rational system of quantities and units.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868133 TI - Reference methods for total cholesterol and total glycerol. AB - In internal and external quality assessment of clinical chemical analyses, the use of reference method values is prescribed in the Federal Republic of Germany as a measure of accuracy control. In the field of lipid analyses, reference methods are available for measuring total cholesterol and total glycerol in control sera. The reference measurement procedures are based on the highly accurate analytical principle of isotope dilution mass spectrometry. A very detailed protocol that ensures a high level of reliability must be followed when reference measurement procedures are carried out. The introduction of reference methods as a basis for accuracy control has greatly limited the unacceptable use of inaccurate routine methods. PMID- 1868134 TI - Sex difference in whole-body androgen content in rats on fetal days 18 and 19 without evidence that androgen passes from males to females. AB - The whole-body content of androgen (testosterone + 5 alpha-dihydrotestosterone) was significantly higher on Fetal Days 18 and 19 in male than in female rats; androgen content was equivalent in the two sexes at other fetal ages, including Days 16, 17, 20, and 21, and prior to parturition on Fetal Day 22. These results partially corroborate previous data of Weisz and Ward (Endocrinology 1980; 106:306-316), who measured testosterone in pooled plasma from rat fetuses and suggest that androgens contribute to masculine brain sexual differentiation only briefly during fetal life. No significant differences in whole-body androgen content were observed among groups of females situated in utero between 0, 1, or 2 males on each side (contiguous male model) or among groups of females with 0, 1, or 2 or more males located caudally (on the cervical side) in the same uterine horn, regardless of whether combined data from Fetal Days 17-22 or only Fetal Days 18 and 19 were considered. These results provide no evidence that androgens from males reach female fetuses in the same uterine horn. PMID- 1868135 TI - Postpubertal maturation of endogenous opioid regulation of luteinizing hormone secretion in the female sheep. AB - This study investigated whether the role of endogenous opioid peptides in the suppression of LH secretion during seasonal anestrus in the sheep changes with age. The experimental approach was to determine the effect of blockade of opioid receptors with naloxone on LH secretion at different times of year within the anestrous season, and to compare responses between seasonally anestrous sheep of different ages. Sheep, all past the normal age of puberty, were ovariectomized before the study and treated s.c. with estradiol implants to provide a fixed estradiol feedback signal. One-year-old females responded to naloxone with a rapid increase in LH pulse frequency in the early (April) and late (August) phases of their first anestrous season. This response was similar to that previously found in prepubertal female sheep. Only 5 of the 8 females responded to the same naloxone challenge in mid anestrus (June), suggesting that the contribution of opioid pathways to the inhibition of LH secretion at this time of year is not necessarily the same as that in early and late anestrus. None of the older anestrous sheep (greater than or equal to 2 yr) responded to naloxone in June, indicating age-related changes in the role of endogenous opioid mechanisms in the inhibition of LH secretion. Ovary-intact mature sheep did not respond to naloxone, in contrast to our previous observations in intact prepubertal females. We infer that the neural mechanisms underlying the superficially similar hypogonadotropic states that occur during the prepubertal period, first anestrous season, and later anestrous seasons are not identical.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868136 TI - Diurnal rhythmicity of norepinephrine activity associated with the estradiol stimulated luteinizing hormone surge: effect of age and long-term ovariectomy on hemispheric asymmetry. AB - The age-related decline in female reproductive capacity in rats is accompanied by an inability to respond positively to estradiol (E2) treatment. This age-related change is associated with a loss in diurnal rhythmicity of norepinephrine (NE) activity in brain areas important in the control of LH. Decreased exposure to ovarian secretions during adulthood delays certain aspects of neuroendocrine aging. We tested the hypothesis that long-term ovariectomy (OVX) would delay the age-related loss of diurnal rhythmicity in NE activity in microdissected hypothalamic nuclei. Intrigued by reports of lateralization of hypothalamic function, we also assayed NE activity in the left and right sides of the hypothalamus separately. Young (2-3 mo) and middle-aged (11-12 mo) rats that exhibited regular estrous cycles were OVX. One week later (Day 0) these short term OVX animals (Y-ST, MA-ST) plus a group of middle-aged (11-12 mo) rats that were OVX at 3 mo (MA-LT) were treated with E2. On Day 4, the rate constant of NE activity in microdissected hypothalamic nuclei was determined at 0900 h and 1500 h using the alpha-methyl-para-tyrosine method. Rate constants were compared by t test to determine diurnal rhythmicity. Y-ST rats exhibited a diurnal rhythm in NE activity in the median eminence, which was absent in MA-ST rats. Long-term OVX spared animals this "age-related" loss in rhythmicity since MA-LT rats demonstrated a significant increase in NE activity from morning to afternoon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868137 TI - Calcium-dependent and calcium-independent gelatinolytic proteinase activities of the rat ventral prostate and its secretion: characterization and effect of castration and testosterone treatment. AB - Calcium-dependent and calcium-independent proteinase activities were detected in extracts of rat ventral prostate and its secretion by use of gelatin-containing SDS-PAGE zymography. Ca(2+)-independent proteinase activities of 22, 26, and 73 79 kDa and Ca(2+)-dependent activities of 58, 63, and 66 kDa were found in the adult gland. The 26- (most intense activity of gland) and 22-kDa activities were present in secretion and were not expressed in the undifferentiated gland of the 10-day-old animal. The Ca(2+)-dependent activities were also present in the secretion, where the 63-kDa form was more prominently expressed than the 58- and 66-kDa bands. The Ca(2+)-dependent and Ca(2+)-independent proteinase activities both responded to a broad range of pH values in the incubation media. The 73-79 kDa Ca(2+)-independent activities were sensitive to benzamidine and the Ca(2+) dependent activities were inhibited by EDTA and EGTA. Both Ca(2+)-dependent and Ca(2+)-independent proteinase activities responded to androgenic manipulations. Castration was followed by the appearance of a 35-kDa Ca(2+)-independent proteinase (at 2 days) and a 43-kDa Ca(2+)-dependent proteinase (at 4 days). In the Ca(2+)-independent proteinase group, the 73-79-kDa activities were increased somewhat and the 22- and 26-kDa activities decreased after castration. The Ca(2+) dependent proteinases of 58, 63, and 66 kDa increased in activity with castration, but activity of the 58-kDa form decreased again at 7 days after castration. Treatment of animals upon castration for 4 days with hydrocortisone prevented these changes in proteinase activities whereas treatment with actinomycin D or tranexamic acid did not. Testosterone propionate replacement therapy of rats castrated for 16 days stimulated the activities of the 22- and 26 kDa and 73-79-kDa Ca(2+)-independent and the 58- and 63-kDa Ca(2+)-dependent proteinases with 4 days of therapy. The activities of the 35-kDa Ca(2+) independent and the 43-kDa Ca(2+)-dependent proteinases were repressed with 8 days of testosterone treatment. Thus, individual proteinases show differential changes in activity during development and in response to androgenic manipulation: this suggests that in addition to proteinases which are secreted, others may be involved in intracellular functions or in mediating tissue organization changes. PMID- 1868138 TI - Plasma patterns of prolactin, progesterone, and estradiol during early pregnancy in aging rats: relation to embryonic development. AB - Regularly cyclic, middle-aged female rats exhibit a decreased incidence of fertility, and those females that are fertile produce smaller litters. This decreased litter size is directly related to a reduced number of normal blastocysts available for implantation. Recent evidence indicates that embryonic abnormalities in middle-aged rats become apparent as early as Day 2 of pregnancy. Inasmuch as the semicircadian secretion of prolactin (PRL) is essential for the rescue of corpora lutea during early gestation and luteal production of progesterone (P) and estradiol (E2) in sufficient quantities is obligatory for embryonic development and implantation, the present study examined the profiles of plasma PRL, P, and E2 during the first 3 days of pregnancy in both young and middle-aged rats and assessed the embryonic development in these same animals. Regularly cyclic, middle-aged (9-11 mo) and young (4-5 mo) rats were cannulated via the right jugular vein on Diestrus Day 2 and mated with fertile males on proestrus. The next morning, sperm in the vaginal lavage confirmed mating, and that day was designated Day 1 of pregnancy. Beginning at 1400 h on Day 1 and continuing to 2400 h on Day 2, serial blood samples were taken at 2-h intervals for PRL assay. In the first experiment, samples were also collected at 8-h intervals during Days 1-3 for measurement of plasma P.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868139 TI - Leukocyte supplementation increases the luteinizing hormone-induced ovulation rate in the in vitro-perfused rat ovary. AB - Ovaries from eCG-primed (20 IU s.c. on Day 28) rats were perfused from the morning of Day 30 of age in a recirculating system initially containing a buffered blood cell-free medium (M199 + 4% BSA) for periods of up to 21 h. The addition of ovine LH (0.1 micrograms/ml) at 0 h of perfusion resulted in ovulations in all 6 ovaries perfused (3.2 +/- 0.7 ovulations per treated ovary; mean +/- SEM), whereas none of the 6 control ovaries ovulated. Rat leukocytes (50 x 10(6)), added at 7 h of perfusion significantly increased the number of LH induced ovulations (7.8 +/- 0.5; p less than 0.05). All ovulated oocytes showed resumption of meiosis as judged from the presence of germinal vesicle breakdown. Ovaries perfused with leukocytes but without LH did not ovulate. Histological examination of ovaries 14 h after leukocyte administration showed a considerable number of perifollicular extravasated white blood cells. These findings indicate that leukocytes participate in the normal ovulatory process as part of an inflammation-like reaction. PMID- 1868140 TI - Localization of sperm antigen SP-10 during the six stages of the cycle of the seminiferous epithelium in man. AB - The distribution of the sperm protein SP-10 was investigated in plastic-embedded samples of human testes by light and electron microscopy. An immunogold and silver enhancement technique, in conjunction with a monoclonal antibody (MHS-10) raised against SP-10, was used to localize the protein. SP-10 was detected in spermatids at each of the six stages of the cycle of the seminiferous epithelium. Light microscopy showed immunoreactive material at the circumference of developing acrosomes in the early steps of spermiogenesis. As differentiation proceeded and cell shape changed from round to elongated, immunoreactive material appeared in an arc, which gradually became a V shape bordering the spermatid nucleus. The area of the immunoreactive material and its shape corresponded to that of the developing acrosome. At the electron microscopic level, gold particles indicative of the presence of SP-10 were detected on electron-dense material found within the developing acrosomal vesicle in early steps of spermiogenesis. As the electron density of the acrosome increased, a high concentration of gold particles was seen in the vesicle matrix. The gold particles gradually became associated with the inner and outer acrosomal membranes of the most mature spermatids. PMID- 1868141 TI - Mouse granulated metrial gland cells originate by local activation of uterine natural killer lymphocytes. AB - Natural killer (NK) lymphocytes were identified in the mouse uterus by immunostaining their surface membrane marker, LGL-1. The cells were present in large numbers from before mating through Day 14 of pregnancy. Double immunostaining indicated that uterine NK cells began to contain the pore-forming protein, perforin, on Day 6 of pregnancy in mesometrial decidua. Perforin is a probable mediator of cellular cytotoxicity found in lymphokine-activated NK and cytotoxic T lymphocytes. Activation of NK cells to produce perforin continued in mesometrial decidua on Days 8 and 10 of pregnancy and in the peripheral portion of metrial glands (MGs) on Days 12 and 14 of pregnancy, where cells at 3 stages of activation were simultaneously present: small cells with bright surface membrane staining of LGL-1 but no perforin (nonactivated), larger cells with intermediate staining of both markers (partially activated), and large cells with bright staining of perforin but no LGL-1 (fully activated). These observations indicate that activation of uterine NK cells involves loss of membrane LGL-1 as perforin accumulates in the cytoplasm, that the zone of activation shifts from mesometrial decidua to the MG on about Day 11 of pregnancy, and that nonactivated NK cells probably enter activation zones continuously during this period. Resting NK cells may enter activation zones by proliferation and/or migration from other regions of the uterus, rather than from blood, because depletion of circulating NK cells during pregnancy by treatment with NK-1.1 or asialo GM1 antibodies had no effect or only a small effect on the numbers of LGL-1-or perforin-positive cells seen in the uterus later in pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868142 TI - Presence and role of c-myc proto-oncogene product in mammalian sperm cell function. AB - The presence and role of c-myc protein was investigated in mature sperm cells of the human, mouse, and rabbit. The monoclonal antibodies against c-myc protein (c myc) reacted with the acrosomal region of the sperm of these mammalian species in the indirect immunofluorescence technique. The c-myc monoclonal antibody (MCA) recognized c-myc protein of 62 and 64 kDa on Western blots of lithium diiodosalicylate-solubilized sperm preparations of these species. The c-myc MCA showed a dose-dependent inhibition of human sperm penetration of zona-free hamster eggs, inhibition of murine in vitro fertilization, and reduced in vivo fertilization in rabbits. There was no effect of the antibody on percent sperm motility, though the antibody significantly affected various motility characteristics such as mean and maximum amplitude of lateral head displacement and curvilinear velocity involved in hyperactivation phenomenon of human sperm cells. These results suggest that c-myc or c-myc-like protein is present in mature sperm cells and may have a role in sperm cell function especially in capacitation and/or acrosome reaction. PMID- 1868143 TI - In vitro DNA synthesis by isolated preantral to preovulatory follicles from the cyclic mouse. AB - In recent studies, we have shown that the smallest preantral follicles in the cyclic hamster increase DNA synthesis in the periovulatory period in response to surge levels of FSH. The current investigation was designed to determine whether the same phenomenon occurs in the cyclic mouse. Intact mouse follicles were isolated with watchmaker forceps (stages 4-6) or by enzymatic digestion (stages 1 4) at 0900 h and 1500 h on each day of the 5-day estrous cycle. The isolated follicles were classified into 6 stages: stages 1 and 2: follicles with 1 and 2 layers of granulosa cells; stage 3: follicles with 3 or more layers of granulosa cells and formation of theca; stages 4-6: incipient, small, and preovulatory antral follicles. The follicles at each stage were incubated for 3 h with [3H]thymidine. DNA content in stages 1-4 of follicles remained unchanged during the estrous cycle; for stages 5 and 6, DNA content was higher on the afternoon of proestrus than on other days of the cycle. Incorporation of [3H]thymidine for stages 1-3 (preantral follicles) started to increase at 1500 h of proestrus and peaked at 0900 h on estrus, whereas for stages 4-6, DNA synthesis peaked on proestrus (1500 h) and then fell by the morning of estrus. Thus, the rate of DNA replication in preantral and antral mouse follicles were different. Similarities and differences in folliculogenesis between mouse and hamster are discussed. These results suggest that DNA synthesis and the growth of all stages of follicles in the cyclic mouse may be associated with changing levels of periovulatory gonadotropins. PMID- 1868144 TI - The regulation of decidual prostaglandin biosynthesis by growth factors, phorbol esters, and calcium. AB - The production of prostaglandins by decidua may play a significant part in the mechanisms of human parturition. We have evaluated the regulation of prostaglandin production in human decidual cells in monolayer culture. Both epidermal growth factor and transforming growth factor-alpha induced concentration-related increases in decidual prostaglandin production with significant changes occurring at concentrations of 1 to 10 ng/ml. Two active phorbol esters elicited concentration-related increases in decidual prostaglandin production whereas an inactive phorbol analogue was without effect. The calcium ionophores, ionomycin and A-23187, also stimulated prostaglandin production by human decidual cell cultures. Hence prostaglandin production by human decidua is regulated by hormones and agents in a manner similar to that of other cells including amnion and may play a significant part in the mechanism of parturition. PMID- 1868145 TI - Melatonin suppression of mammary growth in heifers. AB - The objective of this study was to determine if melatonin fed in the middle of a long day (16L:8D) reduces mammary parenchymal growth and reduces serum prolactin in prepubertal heifers, thereby mimicking the effects of a short photoperiod. Sixteen prepubertal Holstein heifers were maintained under natural May to August environmental conditions of Michigan plus supplemental lighting to provide a photoperiod of 16L:8D (lights-on 0600-2200 h). At the midpoint of each day, 8 animals were individually fed melatonin (4 mg/100 kg body weight) and 8 were individually fed vehicle (95% ethanol) in 200 g of a grain concentrate mixture. Blood samples were collected at 1-h intervals for 25 h beginning on Day 67. On Day 70 or 72 heifers were slaughtered. No differences were found in body weight gain between melatonin- and vehicle-fed animals. Parenchyma of mammary glands from melatonin-fed heifers had a lower content (24%) and concentration (17%) of deoxyribonucleic acid but a greater concentration of triglyceride (24%) than that of controls. Mean serum prolactin concentration was 27% lower in melatonin-fed animals. In both groups, serum concentrations of prolactin varied throughout the day, with greatest values occurring between 1100 and 1800 h in positive association with changes in ambient temperature. We conclude that melatonin orally administered to prepubertal heifers reduced mammary parenchymal growth and concentration of prolactin in serum. The data support the hypothesis that melatonin mimics photoperiodic effects on mammary growth and prolactin secretion in cattle. PMID- 1868146 TI - Hormonal regulation of rat granulosa cell deoxyribonucleic acid synthesis: effects of estrogens. AB - Although it is widely accepted that estrogens exert a major trophic effect on follicular growth, their mechanism of action has not been established. We examined the effect of estrogen treatment in vivo or in vitro on DNA synthesis in rat granulosa cells cultured under defined conditions (DMEM:F12, collagen-coated plastic wells). Treatment with diethylstilbestrol (DES) in vivo (silastic implants containing 5 mg DES) for at least 2 days was required to observe a significant stimulation of 3H-thymidine incorporation by insulin (1 microgram/ml) in culture. Rat thecal/interstitial cells (TI) were isolated from DES-treated rats and cultured under the same conditions as granulosa cells. Conditioned media from TI cells stimulated DNA synthesis in granulosa cell cultures (as much as twofold). This effect was markedly amplified by estradiol treatment (1 microgram/ml) of the TI cell cultures. Addition of estradiol to granulosa cell cultures enhanced the effect of conditioned medium from nontreated TI cells. Conditioned medium from estradiol-treated TI cells stimulated DNA synthesis in granulosa cells from both DES-treated and nontreated rats. Estradiol had no effect when added directly to purified granulosa cell cultures but stimulated 3H thymidine incorporation in crude preparations of ovarian cells. The stimulatory effects of TI cell-conditioned medium and insulin were reflected in the final cell densities achieved after 9 days in culture. We conclude that the mitogenic actions of estrogens in the ovary involve sensitization of granulosa cells to locally present mitogens like insulin and a TI cell-derived growth factor. PMID- 1868147 TI - Colony-stimulating factor-1 blocks early pregnancy in mice. AB - To elucidate the mechanisms underlying the suspected immune-related pregnancy failures in humans, we established experimental systems to induce pregnancy blocking and abortion in mice. One system, based on the preimmunization of C57BL/6J females with a syngeneic regressor tumor, is described. Such females fail to develop normal gestations when mated to C57BL/6J x DBA/2 F-1 (B6D2F-1) males or DBA/2 males but sustain normal pregnancies when impregnated by CBA/J or C57BL/6 males. An investigation into the cause of these male-specific pregnancy failures led us to identify colony-stimulating factor-1 (CSF-1) as responsible for both pregnancy-block and resorption of embryos. Indeed, injection of very small amounts of CSF-1 into plugged females, for the first 5 days of pregnancy, was sufficient to block B6D2F-1-induced gestations but had no effect on CBA/J mated females. It also induced a high rate of fetal resorptions in the sensitive mating. These results suggest a novel mechanism underlying pregnancy failures: a mechanism based on cytokines and their effect on early embryonic development in certain mating combinations. PMID- 1868148 TI - Inhibition of the mouse sperm surface alpha-D-mannosidase inhibits sperm-egg binding in vitro. AB - In previous reports from this laboratory, we identified the presence of a novel alpha-D-mannosidase on the surface of rat, mouse, hamster, and human spermatozoa [J Cell Biol 1989; 109:1257-1267 and Biol Reprod 1990; 42:843-858]. Since it has been suggested that mannosyl residues on the egg zona pellucida may be important for sperm-egg binding, studies were undertaken to examine the potential role of the sperm alpha-D-mannosidase during fertilization. Incubation of mouse spermatozoa in the presence of increasing concentrations of the inhibitory sugars, alpha-methyl mannoside, alpha-methyl glucoside, D-mannose, or D-mannitol, resulted in a dose-dependent decrease in the number of spermatozoa bound per egg without a deleterious effect on sperm motility or on the sperm acrosome, and a dose-dependent inhibition of the sperm mannosidase activity. Galactose, however had no effect on sperm-egg binding or on sperm mannosidase activity. Two nucleotide sugars (UDP-GlcNAc and UDP-gal) were also tested and shown to reduce sperm-egg binding but with only a minimal effect on sperm mannosidase activity. In additional studies, spermatozoa incubated in the presence of a mannose containing oligosaccharide exhibited a dramatic reduction in sperm-egg binding that correlated with a similar inhibition of sperm mannosidase activity. The oligosaccharide substrate did not affect sperm motility or the sperm acrosome. These studies suggest that the sperm alpha-D-mannosidase may play an important role during fertilization. PMID- 1868149 TI - Production of progestin-stimulatory factor(s) by enriched populations of rat T and B lymphocytes. AB - We have previously demonstrated that a progestin-stimulatory factor(s) (PSF) is present in the supernate of concanavalin A-activated rat splenocytes. In the absence of FSH, PSF evokes dose-dependent increases in both progesterone and 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P) production by undifferentiated rat granulosa cells while basal estrogen production is unaffected. Because splenocytes are composed predominantly of T and B lymphocytes, we sought to determine if PSF production is restricted to one of these specific cell types. To accomplish this, dispersed splenocytes were prepared from the spleens of adult female rats. Macrophages were removed by standard adherence procedures, and highly enriched populations of T and B lymphocytes were obtained by negative selection panning utilizing monoclonal antibodies to T and B lymphocytes. Purity of the T- and B-cell populations (typically greater than 85-95%) was assessed by single-color flow cytometry. Enriched populations of T cells, B cells, or unseparated lymphocytes were then seeded into tissue culture flasks and stimulated with 2.5 micrograms/ml concanavalin A. Following a 48-h incubation at 37 degrees C, cytokine-rich fractions were prepared from the conditioned medium of these cultures by ammonium sulfate fractionation. The presence of PSF was assessed by the ability of the resulting fractions to specifically stimulate progestin production by undifferentiated rat granulosa cells in vitro. Granulosa cells were treated with increasing doses (ranging from 0-30% v/v) of supernatants from cultures of T cells, B cells, or unseparated splenocytes for 48 h. Media were removed and progesterone, 20 alpha-OH-P, and estrogen levels were quantified by RIA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868150 TI - Steroidogenesis-stimulating activity in the gonads: comparison of rat testicular fluid with bovine and human ovarian follicular fluids. AB - The steroidogenesis-stimulating activities of ovarian follicular fluid from bovine (bFF) and human (hFF) sources, were compared with those of adult rat testicular fluid (rTF) using an in vitro bioassay system based on stimulation of testosterone production by purified adult rat Leydig cells during a 20-h incubation. Rat TF and bFF were charcoal-treated to remove steroids prior to assay, and the major active fraction of hFF was collected after gel-permeation chromatography. All three fluid samples stimulated both basal and maximal hCG stimulated testosterone production, although the resulting log dose-response lines of bFF and the hFF extracts were not parallel with those of rTF. Both rTF and bFF were active over a similar dose range (5.2-150 microliters and 9.7-150 microliters, respectively) and both had a more than additive interaction with hCG on testosterone production. The stimulatory activity of the hFF extract was considerably greater than that of either rTF or bFF in the absence of hCG, but hFF extract had only an additive effect with hCG in stimulating testosterone production. Moreover, unlike rTF activity, which was inhibited by co-incubation with the protein synthesis inhibitor, cycloheximide, the activity of the hFF extract was not affected by cycloheximide. The factors responsible for activity in all three fluids were of a large molecular size (greater than 30 kDa), as determined by ultrafiltration or gel-permeation chromatography. However, in contrast to both rTF and bFF, hFF extract activity was removed by charcoal extraction. Human FF extract was inactivated by heat (100 degrees C, 30 min), whereas rTF activity was partially (70%) heat-labile and bFF was not affected by heart.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868151 TI - Tension and instantaneous stiffness of single muscle fibers immersed in Ringer solution of decreased tonicity. AB - Isometric tension and instantaneous stiffness were measured in frog semitendinosus single muscle fibers in both isotonic and hypotonic Ringer solution. In 0.7 and 0.5 x normal Ringer tension increased 17 and 20%, respectively. There was no corresponding increase in the measured stiffness. The increase in tension in hypotonic Ringer could be reversed by the addition of an osmotic equivalent of sucrose to the bathing solution. These findings suggest that the potentiated tension observed in hypotonic Ringer is due to an increased tension per cross-bridge and not to an increase in the number of attached cross bridges. PMID- 1868152 TI - Reversible condensation of mast cell secretory products in vitro. AB - We have investigated the mechanisms responsible for the condensation and decondensation of secretory products that occur in mast cell secretion. We show here that the hydrated matrix of an exocytosed secretory granule can be recondensed to its original volume by exposure to acidic solutions containing histamine at concentrations that mimic those found in vivo. Recondensation by acidic histamine began in the range of 1-10 mM with a dose response curve that was accurately predicted by a Hill type equation with four highly cooperative binding sites and a half maximum concentration of [Hi++] = 3.9 mM. Recondensation by histamine showed a sigmoidal dependency on pH (critical range pH 5.5-6.5) and was fully reversible. These experiments suggest that histamine, possibly by binding to anionic sites in the protein-heparin complex of the granule matrix, triggers a change in the polymeric structures of the granule matrix from an extended coil to a collapsed globular state. This may be a useful model for understanding the condensation of secretory products into dense core granules and their subsequent decondensation upon exocytosis. PMID- 1868153 TI - Domains and anomalous adsorption isotherms of dipalmitoylphosphatidylcholine membranes and lipophilic ions: pentachlorophenolate, tetraphenylborate, and dipicrylamine. AB - Dipalmitoylphosphatidylcholine (DPPC) vesicles acquire negative surface charge on adsorption of negatively charged pentachlorophenolate (PCP-), and lipophilic ions tetraphenylborate (TPhB-), and dipicrylamine (DPA-). We have obtained (a) zeta potential isotherms from the measurements of electrophoretic mobility of DPPC vesicles as a function of concentration of the adsorbing ions at different temperatures (25-42 degrees C), and (b) studied the effect of PCP- on gel-to fluid phase transition by measuring the temperature dependence of zeta-potential at different PCP- concentrations. The zeta-potential isotherms of PCP- at 25, 32, and 34 degrees C correspond to adsorption to membrane in its gel phase. At 42 degrees C the zeta-potential isotherm corresponds to membrane in its fluid phase. These isotherms are well described by a Langmuir-Stern-Grahame adsorption model proposed by McLaughlin and Harary (1977. Biochemistry. 15:1941-1948). The zeta potential isotherm at 37 degrees C does not follow the single-phase adsorption model. We have also observed anomalous adsorption isotherms for lipophilic ions TPhB- and DPA- at temperatures as low as 25 degrees C. These isotherms demonstrate a gel-to-fluid phase transition driven by ion adsorption to DPPC membrane during which the membrane changes from weakly to a strongly adsorbing state. The anomalous isotherm of PCP- and the temperature dependence of zeta potential can be described by a two-phase model based on the combination of (a) Langmuir-Stern-Grahame model for each phase, (b) the coexistence of gel and fluid domains, and (c) depression of gel-to-fluid phase transition temperature by PCP-. Within the anomalous region the magnitude of zeta-potential rapidly increases concentration of adsorbing species, which was characterized in terms of a Esin Markov coefficient. This effect can be exploited in membrane-based devices. Comments are also made on the possible effect of PCP, as an uncoupler, in energy transducing membranes. PMID- 1868154 TI - Dipole interactions in electrofusion. Contributions of membrane potential and effective dipole interaction pressures. AB - The contributions of pulse-induced dipole-dipole interaction to the total pressure acting normal to the membranes of closely positioned pronase treated human erythrocytes during electrofusion was calculated. The total pressure was modeled as the sum of pressures arising from membrane potential and dipole-dipole attraction opposed by interbilayer repulsion. The dipole-dipole interaction was derived from the experimentally obtained cell polarizability. The threshold electric field amplitude necessary for fusion of pronase-treated human erythrocytes was experimentally obtained at various combinations of pulse duration, frequency, and the conductivity of the external medium. The theoretical values of the critical electric field amplitude compared favorably to the experimentally obtained threshold field amplitudes. Fusion by dc pulses may be primarily attributed to attainment of sufficiently high membrane potentials. However, with decreasing external conductivity and increasing sinusoidal pulse frequency (100 kHz-2.5 MHz), the induced dipole-dipole interactions provide the principal driving force for membrane failure leading to fusion. PMID- 1868155 TI - Refinement of the main chain directed assignment strategy for the analysis of 1H NMR spectra of proteins. AB - The underlying basis of the main chain directed (MCD) resonance assignment strategy for the analysis of 1H NMR spectra of proteins is reexamined. The criteria used in the construction of the patterns used in the MCD method have been extended to increase the robustness of the approach to the presence of variable protein secondary structure and significant spectral degeneracy. These criteria have led to the development of several dozen patterns exclusively involving the short distance relationships between main chain amide NH-C alpha-H C beta H (NAB) J-coupled subspin systems of the amino acid residues. The MCD patterns have been examined for fidelity and frequency of occurrence in a database composed of the high resolution crystal structures of 39 proteins. The analysis has identified several extremely robust patterns, suitable for initiating a hierarchical construction of units of secondary structure based upon a systematic analysis of two-dimensional nuclear Overhauser effect spectra. A formal procedure, suitable for the computer assisted application of the MCD strategy, is developed. This procedure, termed MCDPAT, has been applied to the analysis of the crystal structures of human ubiquitin, T4 lysozyme, and ribonuclease A. It has been found that the MCDPAT procedure is conservative producing no significant errors and is globally successful in correctly identifying the appropriate units of secondary structure contained in these three proteins. PMID- 1868156 TI - Implementation of the main chain directed assignment strategy. Computer assisted approach. AB - A computer-assisted procedure has been developed to apply the main chain directed (MCD) assignment strategy to the analysis of 1H NMR spectra of proteins. The underlying mathematical foundation of this procedure, termed MCDPAT, is presented. MCDPAT is based upon the expanded library of MCD patterns defined previously (A.J. Wand and S.J. Nelson. 1991. Biophys. J. 59:1101-1112), and has been evaluated with both simulated and experimental data from the protein ubiquitin. The influence of the precision, spectral variation, and inherent degeneracy upon the design of the procedure is explored. Several approaches have been taken to overcome the uncertainty introduced by these variables. These include a hierarchical approach to both primary pattern recognition and subsequent construction of MCD-defined units of secondary structure. It is shown that the MCDPAT procedure, in conjunction with automated statistically based spectral analysis, leads to the successful MCD assignment of the protein ubiquitin. The implications and limitations of this approach are discussed. PMID- 1868158 TI - Effect of basic oligopeptides on the B-Z transition of poly(dG-dC). poly(dG-dC) in water-methanol solutions. AB - The effect of basic oligopeptides (Lys-Ala-Ala)n (n = 1-5, 10) and (Lys-Leu-Ala)n (n = 1-4) on the B-Z transition of poly(dG-dC).poly(dG-dC) in water-methanol solutions was investigated using CD and uv spectroscopy. In the absence of peptides, the concentration of methanol at the midpoint of the B-Z transition is 64% at 25 degrees C. The transition is temperature dependent and the B conformation is preferred at higher temperatures. All peptides tested shift the midpoint of the B-Z transition to lower concentrations of methanol. For shorter peptides this effect increases with an increasing number of monomeric units, showing the importance of the number of positive charges in the peptide molecule. Al conditions of low methanol content, the trimer and tetramer of the (Lys-Leu Ala)n series have a greater effect on the B-Z transition than the corresponding oligomers of the (Lys-Ala-Ala)n series. This indicates an important influence of the presence of hydrophobic groups in the peptide side chains on the binding. In the presence of peptides, the B-Z transition is also temperature dependent and the B conformation is preferred at higher temperatures. The addition of peptides results in an increase of the transition midpoint and of the transition width. These parameters were used for the calculation of the transition enthalpy delta HB-Z in 65% methanol, which is -1.15 +/- 0.25 kcal/base pair. Since the van't Hoff enthalpy delta HVH calculated from the temperature dependence of the B-Z transition in the absence of peptides is -130 kcal/mol, the length of the cooperative unit is about 110 base pairs. The results suggest that the mechanism of Z-DNA induction is similar but not identical with that involved in the action of metal cations in aqueous solution. PMID- 1868157 TI - Restoring forces in cardiac myocytes. Insight from relaxations induced by photolysis of caged ATP. AB - Concentration jumps of intracellular ATP were produced by photolysis of P3-1-(2 nitrophenyl)ethyl (NPE)-caged ATP and were used to investigate the passive relengthening properties in unloaded cardiac myocytes. Patch-clamp pipettes in the whole-cell mode were used to voltage-clamp the myocytes and to load the cells with caged ATP while optical methods were applied to record sarcomere length or cell length simultaneously. Cell length was varied using energy deprivation contractures while intracellular Ca2+ was controlled with EGTA. At sarcomere lengths between 1.8 and 1.4 microns cellular relengthening after photolysis of caged ATP was rapid (t1/2 approximately 100 ms) and could be well described by a simple mechanical model. However, ATP jumps made at sarcomere lengths approximately 1.1 microns led to slow relengthening (t1/2 approximately seconds), comparable to the slow reextensions observed in skinned myocytes after bulk solution changes. We attribute the slow and incomplete relengthening of intact and skinned myocytes after severe rigor shortening to deformation and alteration of structural elements inside the cell. Relengthening from intermediate sarcomere lengths in intact cells is elastic and provides information about the underlying relengthening forces inside the cell. The data do not support the presence of a significant discontinuity in elastic modulus at a sarcomere length of approximately 1.6 microns expected from ultrastructural features of the sarcomeres and from observations in skinned myocytes. Our results suggest that the cell length measurements usually performed in this preparation provide an adequate description of the force produced by the unloaded cell in the steady state. The results also provide a way to estimate the error arising from viscous forces during rapid shortening. PMID- 1868159 TI - Molecular dynamics simulations of small peptides: dependence on dielectric model and pH. AB - There has been much interest recently in the structure of small peptides in solution. A recent study by Bradley and co-workers [(1989) in Techniques of Protein Chemistry, Hugli, T.E., Ed., Academic Press, Orlando, FL, pp. 531-546; (1990) Journal of Molecular Biology, 215, pp. 607-622] describes a 17-residue peptide that is stable as a monomeric helix in aqueous solution at low pH, as determined by two-dimensional nmr and CD spectroscopy. They also have determined the helix content of the peptide as a function of pH using CD. We performed molecular dynamics simulations, with an empirical force field, of this peptide at low pH, with three different dielectric models: a linear distance-dependent dielectric function (epsilon = R); a modified form [J. Ramstein and R. Lavery (1988) Proceedings of the National Academy of Science, USA, Vol. 85, pp. 7231 7235] of the sigmoidal distance-dependent dielectric function of Hingerty and co workers [(1985) Biopolymers, Vol. 24, pp. 427-439]; and epsilon = 1 with the peptide immersed in a bath of water molecules. We found that simulations with the sigmoidal dielectric function and the model with explicit water molecules resulted in average distances for particular interactions that were consistent with the experimental nmr results, with the sigmoidal function best representing the data. However, these models exhibited very different helix-stabilizing interactions. We also performed simulations using the sigmoidal function at moderate and high pH to compare to experimental determinations of the pH dependence of helix content. Helix content did not decrease with increases in pH, as shown experimentally. We did, however, observe changes in a specific side chain-helix dipole interaction that was implicated in determining the pH dependent behavior of this peptide. Overall, the sigmoidal dielectric function was a reasonable alternative to adding explicit water molecules. In comparing 100 ps molecular dynamics simulations, the sigmoidal function was much less computer intensive and sampled more of conformational space than the treatment using explicit water molecules. Sampling is especially important for this system since the peptide has been shown experimentally to populate both helical and nonhelical conformations. PMID- 1868160 TI - The electrostatically driven Monte Carlo method: application to conformational analysis of decaglycine. AB - The Electrostatically Driven Monte Carlo (EDMC) method was applied in a study of a decamer of glycine whose conformational behavior is described by the Empirical Conformational Energy Program for Peptides (ECEPP/2) potential energy model. When free neutral end groups were used, it was found that conformations that were not alpha-helical had significantly lower potential energies than fully alpha-helical ones. However, when the N- and C-termini were blocked by acetyl and methyl amide groups, respectively, the number of unsatisfied hydrogen-bond donors and acceptors at the helix termini was diminished from 8 to 6; in this case, the possibility of forming two additional alpha-helical hydrogen bonds was an important enough factor in making the alpha-helical conformation the one with the lowest energy. The EDMC method was used as a global energy optimizer since it does not often become trapped in high-energy local minima. PMID- 1868161 TI - 1H- and 31P-NMR studies of ditercalinium binding to a d(GCGC)2 and d(CCTATAGG)2 minihelices: a sequence specificity study. AB - The structures of the complexes formed in aqueous solution between ditercalinium, a bis-intercalating drug, and both the self-complementary tetranucleotide d(GCGC)2 and octanucleotide d(CCTATAGG)2, have been investigated by 400-MHz 1H nmr and 162-MHz 31P-nmr. All the nonexchangeable protons, as well as the exchangeable imino protons and the phosphorus signals, have been assigned. Both oligonucleotides have been shown to adopt a right-handed B-DNA type structure. The addition of ditercalinium to the oligonucleotides lead to the formation of complexes in slow exchange at the nmr time scale with the free helices. At all drug-to-helix ratios studied, the ditercalinium was found in the bound form, whereas free and complexed oligonucleotides were in slow exchange, allowing resonance assignments through two-dimensional chemical exchange experiments. for d(GCGC)2 the strong upfield shifts induced on all aromatic protons of both the bases and the drug by complexation with ditercalinium suggest an interaction by intercalation of the two rings. However, the loss of twofold symmetry upon binding, as well as the chemical shift variation of the drug proton signals of one of the chromophores with temperature and concentration, favor a model in which the drug-nucleotide complexes have one ring of the drug intercalated and the other stacked on top of the external base pair. The intermolecular contacts between drug protons and nucleotide protons give a defined geometry for complexation that is consistent with the proposed model. In contrast, with d(CCTATAGG)2 several drug-nucleotide complexes were formed and a large increase in line broadening was observed at high drug-to-DNA ratios, precluding a detailed analysis of these complexes. However, the large upfield shift in the imino proton resonances together with the shielding of the ditercalinium ring protons favor a model with bis-intercalation of ditercalinium. This model is supported by the downfield shift of at least 4 out of 14 phosphorus signals. The results are compared with those obtained on ditercalinium binding to the homologous sequences d(CGCG)2 and d(TTCGCGAA)2, and discussed in terms of sequence specificity. PMID- 1868162 TI - Observation of preferred direction melting in a lattice model of poly(dA dC).poly(dG-dT). PMID- 1868163 TI - Differential scanning calorimetry studies of NaCl effect on the inverse temperature transition of some elastin-based polytetra-, polypenta-, and polynonapeptides. AB - Differential scanning calorimetry studies of the effect of NaCl on protein-based polymer self-assembly has been carried out on six elastin-based synthetic sequential polypeptides--i.e., the polypentapeptide (L-Val1-L-Pro2-Gly3-L-Val4 Gly5)n and its more hydrophobic analogues (L-Leu1-L-Pro2-Gly3-L-Val4-Gly5)n and (L-Val1-L-Pro2-L-Ala3-L-Val4-Gly5)n; the polytetrapeptide (L-Val1-L-Pro2-Gly3 Gly4)n and its more hydrophobic analogue (L-Ile1-L-Pro2-Gly3-Gly4)n; and the polynonapeptide (a pentatetra hybrid), (L-Val1-L-Pro2-Gly3-L-Val4-Gly5-L-Val6-L Pro7-Gly8-Gly9++ +)n. Previous physical characterizations of the polypentapeptides have demonstrated the occurrence of an inverse temperature transition since increase in order of the polypentapeptide, as the temperature is raised from below to above that of the transition, has been repeatedly observed using different physical characterizations. In the present experiments, it is observed that the transition temperatures of the polypeptides studied are linearly dependent on NaCl concentration. The molar effectiveness of NaCl in shifting the transition temperature delta Tm/[N], is about 14 degrees C/[N], with the dependence on peptide hydrophobicity being fairly small. Interestingly, however, the delta delta Q/[N] does depend on the hydrophobicity of a polypeptide. PMID- 1868164 TI - A scanning calorimetric study of the thermally induced unfolding of various forms of tropomyosin. AB - The reversible thermally induced unfolding of various forms of tropomyosin, a two chain alpha-helical coiled coil, has been studied by high-sensitivity differential scanning calorimetry (DSC). Included in the study are the reduced and oxidized (disulfide cross-linked) forms of alpha alpha- and beta beta tropomyosin, and the forms of alpha alpha-tropomyosin in which all sulfhydryl groups have been blocked by carboxymethylation or carboxyamidomethylation. Oxidation or blocking of the sulfhydryl groups of tropomyosin strongly affect the thermotropic behavior of the protein in unpredictable ways. The empirical results presented here are in qualitative agreement with those from an earlier DSC study of the oxidized and carboxymethylated forms of alpha alpha-tropomyosin [S.A. Potekhin and P.L. Privalov (1982) Journal of Molecular Biology, Vol. 159, pp. 519 535], but we find that a different decomposition into subtransitions is possible. Comparison of the alpha alpha and beta beta species indicates, in agreement with extant CD studies, that the noncross-linked beta beta species is somewhat less stable than its alpha alpha counterpart, but that cross-linking enhances the stability of the beta beta doubly cross-linked species by a greater amount and does not lead to the small low-temperature transition ("pretransition") seen in the singly cross-linked alpha alpha species. PMID- 1868165 TI - Local structures in unfolded lysozyme and correlation with secondary structures in the native conformation: helix-forming or -breaking propensity of peptide segments. AB - CD spectra of reduced and S-3-(trimethylated amino) propylated lysozyme (TMAP lysozyme) have been measured in various solutions containing guanidine hydrochloride or trifluoroethanol (TFE). The CD spectra indicate that there remain residual secondary structures in protein in aqueous solution. The addition of TFE further promotes the formation of secondary structures. In order to examine whether secondary structures are evenly induced over all the polypeptide chain, or locally at particular segments, the limited proteolysis of TMAP lysozyme by trypsin has been performed, and the CD spectra of all the final and intermediate products have been observed in solutions containing TFE. As a result, the fragments vary in a helix-forming propensity. The CD spectra of peptide fragments T5, T7, T9T10, T12T13, T14T15T16, and T17T18 are not significantly affected by the addition of TFE, where T refers to the nomenclature of R.E. Canfield [(1963), Journal of Biological Chemistry, Vol. 238, pp. 2691 2697]. They are fragments of a helix-breaking propensity. On the other hand, fragment I2 composed of T1-T4, and fragments T6T7, T8, and T11, attain secondary structures with the addition of TFE. They are fragments of a helix-forming propensity. Further, it is found that the fragments of a helix-forming propensity just correspond to the helical segments in native lysozyme. We examine the interactions between neighboring fragments, which contribute to the stabilization of local structures along the polypeptide chain. PMID- 1868166 TI - Oligopurine.oligopyrimidine tracts do not have the same conformation as analogous polypurine.polypyrimidines. AB - The ability of tracts of synthetic oligopurine.oligopyrimidines containing both adenosine and guanosine residues to approach the conformation of analogous polypurine.polypyrimidines has been examined as a function of tract length by CD spectroscopy. Tracts of up to 19 contiguous, alternating dA and dG residues yield CD spectra that are distinctly different from that of the analogous alternating polymer. Thus the structural changes reflected in the unusual CD spectrum of poly[d(AG)].poly[d(CT)] must require even longer tract lengths. Tracts of contiguous adenosines flanked by guanosine residues were seen to approach the CD spectrum of poly[dA].poly[dT] quite slowly as a function of tract length, requiring more than 24 contiguous adenosines to give CD spectra similar to the homopolymer. These results lead us to the conclusion that oligopurine tracts in vivo are not well modeled by synthetic polypurine.polypyrimidines with one or two base pair repeating units. PMID- 1868167 TI - Thermodynamics of drug-DNA interactions: entropy-driven intercalation and enthalpy-driven outside binding in the ellipticine series. AB - Viscosimetric and kinetic results allow one to characterize three modes of DNA binding in the ellipticine series: (1) Ellipticine and its 9 methoxy derivative, which present maximal DNA lengthening properties and bind DNA through a single step mechanism, can be considered as pure intercalators. (2) Ellipticinium derivatives and short-chain substituted oxazolopyridocarbazoles, which present intermediate DNA lengthening properties, bind DNA through a two-step mechanism, one being intercalation. (3) Long-chain substituted oxazolopyridocarbazole derivatives, which display the smallest DNA lengthening properties, bind DNA through a single-step mechanism, probably resulting from an outside binding mode. The viscosimetric and kinetic results are compared with the thermodynamic results obtained from the temperature dependence of the binding constants. It appears that drugs binding on the outside of the DNA double helix tend to have large enthalpy and small entropy contributions, whereas pure intercalating drugs have contributions from both enthalpy and entropy, with entropy dominating by about 2:1. Drugs showing two binding modes exhibit a continuum between the aforementioned extremes, with no breaks in behavior. From this comparison, a correlation between thermodynamic data and DNA binding modes is proposed. Possible molecular implications of both enthalpy and entropy to DNA binding free energy are discussed. PMID- 1868168 TI - Effects of proline ring conformation on theoretical pi-pi* absorption and CD spectra of helical poly(L-proline) forms I and II. AB - Absorption and CD spectra of the pi-pi* transition near 200 nm are calculated for helical (Pro)10 forms I and II with a variable proline ring conformation characterized by torsion angle chi 2 in the range -60 degrees to 60 degrees. The spectra for poly(Pro) I are not sufficiently sensitive to chi 2 to suggest a preferred ring conformation. The spectra for poly(Pro) II are more sensitive to chi 2, and suggest preferred ring conformations near either or both of the chi 2 regions -50 +/- 10 degrees and 50 +/- 10 degrees. PMID- 1868169 TI - Dynamic light scattering from weakly bending rods: estimation of the dynamic bending rigidity of the M13 virus. AB - A theory is presented for the dynamic structure factor [S(K,t]) of weakly bending rods. This treatment is based on a discrete bead model for the Brownian dynamics in which all bead motions associated with bending are constrained to occur in a plane perpendicular to the end-to-end vector, thus prohibiting extension or contraction along that axis. Preset hydrodynamic interactions are incorporated in a numerically exact manner. The predicted normalized dynamic structure factor S(K,t)/S(K,0) should be valid for short times t such that the rms rotation of the end-to-end vector around any transverse axis is much less than 1.0 radian. With geometrical parameters appropriate for the M13 virus, the intensity autocorrelation function G(2) (K,t) = 1 + magnitude of S(K,t)/S(K,0)2 is calculated over a range of times and scattering vectors K for selected values of the persistence length P. The calculated G(2) (K,t) are fitted to a single exponential with unit baseline over the same range of times as the experimental photon correlation functions, and the apparent diffusion coefficients Dapp (K) are obtained from the best-fit relaxation times. For the sake of completeness, an exact expression is derived for the apparent diffusion coefficient obtained from the initial slope of the dynamic structure factor. However, this does not reduce to the known correct result in the rigid rod limit. To obtain the correct result, the limit of infinite bending rigidity must be taken before the limit of zero time. For this and other reasons, the initial slope value of Dapp (K) is not useful for weakly bending rods. Photon correlation functions are measured for the M13 virus, which is virtually identical to the often-studied fd virus. The experimental photon correlation functions are fitted over 8 relaxation times to a single-exponential plus baseline, and the Dapp (K) are calculated from the best fit relaxation times. Theoretical curves of Dapp (K) vs K2 for selected values of P are compared with the experimental data, which are satisfactorily reproduced when P = 22000 +/- 2000 A. This dynamic value is close to the static value, P = 20000 +/- 2000 A, reported for the very similar fd virus. The most recent theories of Maeda and Fujime and their dynamic light scattering studies of fd virus are compared with the present results in some detail. Their optimum value of P is in surprisingly good agreement with the present value. PMID- 1868170 TI - Theoretical CD studies of polypeptide helices: examination of important electronic and geometric factors. AB - An improved model for calculating the CD of polypeptides has been developed. Excited state wavefunctions were derived from CNDO/S (complete neglect of differential overlap, spectroscopic) calculations on N-methylacetamide. Four discrete peptide-localized transitions were employed: pi 0 pi* (NV1), pi* + pi* (NV2), n pi*, and n' pi*. Inclusion of the pi + pi transition (lambda 0 = 140 nm) significantly improves the accuracy of the calculated CD spectra in the 180-250 nm region. Spectra were computed for various helical structures, including right handed alpha-, alpha II-, omega-, pi-, 3(10-), and poly (proline) I-helices, and the left-handed poly (proline) II-helix. Sensitivity to changes in the peptide backbone geometry and chain length are examined. Electronic factors such as ground-state charge distribution, hybridization effects, and basis set deorthogonalization have been investigated. The nonconservative nature of the poly (Pro) I and II CD spectra is reproduced, and the helix band present in earlier exciton calculations on the alpha-helix has been diminished. PMID- 1868171 TI - Nyctohemeral rhythmicity of type II thyroxine 5'-deiodinase activity in the pineal gland but not in the Harderian gland of the Swiss mouse. AB - Type II thyroxine 5'-deiodinase (5'-D) activity in both pineal and Harderian glands of the Swiss mouse was studied. Pineal 5'-D activity exhibited a nyctohemeral profile with a maximal peak value at 05.00 h, which coincides with that for pineal melatonin production. However, no rhythm of 5'-D activity in the Harderian gland could be found. In pineal gland, light at night inhibited the nocturnal increase in 5'-D activity, while isoproterenol, a beta-adrenergic agonist, could not stimulate the enzyme. In the Harderian gland, neither darkness, nor light or night, or isoproterenol were capable of modifying basal values of 5'-D activity. PMID- 1868172 TI - Identification of a mammalian growth factor as a ribofolate peptide. AB - Thymocyte growth peptide (TGP) promotes DNA synthesis of immature thymocytes. TGP has been purified from sheep, human and calf thymus and recently characterized as an N-terminally blocked nonapeptide. Evidence is presented here that the blocking moiety consists of a formylpteroyl group bound to the N-terminal glutamyl residue of the nonapeptide. The pterin part of the TGP molecule has a ribityl substituent in analogy with riboflavin, which explains the pronounced hydrophilic property of TGP in contrast to unsubstituted and unconjugated folates. The compound can be classified as a ribofolate peptide, a novel class of growth factor. Zn2+ counteracts degradation of the molecule and is required for full biological activity; mass spectrometric data confirm that native TGP contains zinc. PMID- 1868173 TI - L-alanine transport in isolated cells of interscapular brown adipose tissue in rat. AB - The pattern of L-alanine uptake in isolated cells of interscapular brown adipose tissue has been determined. The uptake can be divided into the diffusion component (Kd = 0.55 min-1) and a saturable Na(+)-dependent transport (KM = 0.87 mM and Vmax = 155 nmol/min/10(6) cells). The saturable component can be subdivided into MeAIB-sensitive (KM = 1.63 mM and Vmax = 162 nmol/min/10(6) cells) and MeAIB-insensitive (KM = 3.2 mM and Vmax = 39.5 nmol/min/10(6) cells). This kinetic pattern could indicate the presence of transport system (s) that resemble the commonly described transport systems for alanine uptake in several tissues. PMID- 1868174 TI - Starvation is associated with changes in the elemental composition of the pancreatic beta-cell. AB - By using the proton microprobe technique we have investigated the elemental composition of both pancreatic beta-cells and exocrine pancreas from fed and 24 h or 48 h starved obese hyperglycemic mice. Among the 15 elements measured in the beta-cells both Ca and Fe increased while Mg and S decreased significantly after 24 h of starvation, the effects being more pronounced after 48 h. When animals were starved for 48 h there was a decrease in the contents of Cl, Rb and Cu, whereas that of Al and Mn increased with 152 and 55%, respectively. There was an initial decrease in Na after 24 h of starvation, which was followed by an increase after 48 h. This is in contrast to Cd, which first increased and then decreased to a value lower than that obtained in the fed animal. The content of K showed a small decrease and that of Pb showed an increase only in the 24 h starved group. In the beta-cells the contents of Zn and P did not change subsequent to starvation. In the exocrine pancreas Na, Cl and P decreased after 24 h of starvation and except for Na, the decrease was maintained when the starvation period was increased to 48 h. After 24 h there was a significant, though transient, increase in K, Mg and Rb. With regard to the contents of Zn, Cu and S there was a progressive decrease as the starvation continued. In contrast to the endocrine pancreas the content of Al in the exocrine pancreas did not change after 48 h of starvation. There was no change in islet insulin content subsequent to starvation. The extent to which the observed changes in beta-cell elemental composition is involved in the impaired insulin release associated with starvation, merits further investigations. PMID- 1868175 TI - Differences in L-alanine uptake by livers of Wistar and lean Zucker rats. AB - The L-alanine uptake by livers of Wistar and lean Zucker rats has been studied. The hepatic uptake and fractional extraction rates of alanine were estimated in 50-55 day old rats. No significant differences in amino acid concentrations and blood flows in afferent and efferent liver vessels were seen in lean Zucker rats when compared with Wistar rats. However, the hepatic uptake (1.6 +/- 0.1 and 0.7 +/- 0.1 mumol/min/100 g bw, p less than 0.01) and the fractional extraction (26.8 +/- 2.1 and 15.2 +/- 3.1%, p less than 0.05) were much lower in Zucker than in Wistar rats. The hepatic active transport of L-alanine was determined in vitro using isolated plasma membrane vesicles. Vesicles isolated from livers of lean Zucker rats showed similar values of Km (2.5 +/- 0.7 vs. 2.0 +/- 0.5 mM for Wistar and Zucker respectively, N.S.), but lower values of Vmax when compared with Wistar rats (1.1 +/- 0.1 vs 0.6 +/- 0.005 nmol/mg prot 5 s, p less than 0.01, for Wistar and lean Zucker rats respectively). These results indicate that, the liver of lean Zucker rats concentrates alanine less efficiently than the liver of Wistar rats. This fact correlates well with a lower capacity of the Na(+)-dependent L-alanine transport in liver plasma membrane vesicles from lean Zucker rats. PMID- 1868176 TI - Amino acid composition of human liver mitochondrial membranes in normal and pathological conditions. AB - The amino acid composition of proteins from liver mitochondrial membranes has been studied in patients with normal liver, with biliary diseases and fatty liver, with obstructive jaundice or liver cirrhosis. A characteristic pattern of the amino acid composition in patients with normal liver has been found. In the mitochondrial membranes of patients with fatty liver tryptophan and lysine were decreased while [aspartic acid plus asparagine] and [glutamic acid plus glutamine] were increased compared to their counterpart in the normal liver. In patients with obstructive jaundice of short duration (less than two months) only a slight decrease in methionine content was found, while in the case of liver cirrhosis amino acid composition was markedly changed. PMID- 1868177 TI - Vascular anesthesia: recognized at last. PMID- 1868178 TI - Humoral factors and hemodynamics during cross-clamping of the thoracic aorta. AB - The present study was designed to test the hypothesis that vasoactive compounds produced in the ischemic part of the body below an occluded aorta are responsible for the hemodynamic changes observed during cross-clamping of the thoracic aorta. The experiments were performed on 32 rabbits anesthetized with halothane that underwent experiments with cross-circulation; the blood from the inferior caval veins of rabbits A was pumped into the inferior caval veins of rabbits B. Simultaneously, exactly the same amount of blood was pumped from the jugular vein of rabbits B into the jugular vein of rabbits A. The aorta and inferior vena cava were exposed and then simultaneously cross-clamped directly below the diaphragm. The cross-clamping of the aorta and inferior vena cava in rabbits A was associated with a 29% to 44% increase in mean arterial pressure in rabbits B. The experiments support the hypothesis and suggest that endogenously produced humoral factors are responsible for at least one third to one half of the arterial hypertension that usually develops during aortic cross-clamping. PMID- 1868179 TI - Accidental hyperperfusion of the left carotid artery during CPB. PMID- 1868180 TI - Intraoperative left endobronchial tube positioning. PMID- 1868181 TI - Hemodynamic alterations and regional myocardial blood flow during supraceliac aortic occlusion in dogs with a critical coronary stenosis. AB - The hemodynamic consequences and myocardial blood flow alterations associated with cross-clamping of the thoracic aorta were studied during pentobarbital (control), halothane (1 MAC), and isoflurane (1 MAC) anesthesia in dogs with a critical stenosis of the left circumflex coronary artery. Aortic clamping at the level of the diaphragm resulted in significant and equivalent increases in mean aortic pressure and left atrial pressure during the control clamp, halothane clamp, and isoflurane clamp periods. Likewise, aortic clamping resulted in a significant and equivalent decrease in cardiac output during control-clamp, halothane clamp, and isoflurane clamp. Myocardial contractility as assessed by dP/dt was depressed during halothane and isoflurane anesthesia when compared with control, but no further change in contractility was associated with aortic clamping. No significant alterations in regional or transmural myocardial blood flow were found with halothane or isoflurane anesthesia, or with aortic clamping during halothane or isoflurane anesthesia. It is concluded that there are significant hemodynamic consequences associated with aortic clamping, that neither halothane nor isoflurane anesthesia alters these consequences when compared with pentobarbital anesthesia alone, and that the deterioration in myocardial function observed during aortic clamping with halothane and isoflurane anesthesia cannot be attributed to any maldistribution of myocardial blood flow. PMID- 1868182 TI - New applications of two-dimensional transesophageal echocardiography in cardiac surgery. AB - This article describes new applications of two-dimensional transesophageal echocardiography (2D-TEE), including (1) detection of pleural fluid (PF) and atelectasis (AT), and (2) evaluation of various cannulation techniques. The left and right pleural spaces were visualized by rotating the probe counterclockwise and clockwise, respectively, from the four-chamber view. PF was depicted as a crescent-shaped echo-free space, enclosed by the lung and posterior chest wall on both sides. AT was often accompanied by PF and was depicted as a less echogenic area in the lung parenchyma. During removal of PF, the echo-free space gradually decreased in size to the point of disappearing completely, while the lung parenchyma expanded and became more echogenic. TEE was advantageous in detecting PF and AT located in the most dorsal parts of the pleural space and lung parenchyma. The aorta acted as an acoustic window on the left side. TEE was found useful in evaluating the cannulae position of the intraaortic balloon pump (IABP) and ventricular assist device (VAD), and femoral cannulae for cardiopulmonary bypass (CPB). During use of the IABP, the chamber and shaft were visualized clearly and both malposition of the catheter tip and malfunction of the balloon were easily detected. For VAD, TEE readily showed the collapse of the ventricular cavity due to excessive drainage of blood from the left ventricle, as well as the favorable result of immediate reduction of flow rate. For femorofemoral extracorporeal bypass, TEE detected improper position of the venous cannula. These new applications of TEE can be performed with minimal manipulation of the probe, enabling early detection of the problems and initiating timely and appropriate therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868183 TI - Left ventricular ejection fraction: single-plane and multiplanar transesophageal echocardiography versus equilibrium gated-pool scintigraphy. AB - The relative accuracy and precision of estimating left ventricular ejection fraction (EF) in dogs were assessed by two-dimensional transesophageal echocardiography (2D-TEE) and by three-dimensional transesophageal echocardiographic (3D-TEE) imaging and reconstruction. This assessment was accomplished by comparing each echocardiographic method to a gated equilibrium blood pool radionuclide (RN) standard. By using both correlation and regression analysis, 2D-TEE performed reasonably well in estimating RNEF (correlation coefficient [r] = 0.80, slope = 1.01, intercept = 6.37, standard error of the estimate [SEE], 8.98), but not as well as 3D-TEE (r = 0.86, slope = 0.83, intercept = 3.38, SEE, 5.74). Using Altman and Bland's methods of comparison analysis, it was found that 2D-TEE overestimated RNEF by 7% (standard deviation [SD], 8.8). This degree of overestimation was not consistent across the range of measurement. In contrast, 3D-TEE slightly underestimated RNEF by less than 3% and showed less variability (SD, 6.0). The accuracy of the 3D-TEE determinations was not dependent on the magnitude of EF. Additionally, a significantly higher proportion of the 2D-TEE measurements (0.30) compared with the 3D-TEE measurements (0.10) differed from RN values by more than 10% (P = 0.009, McNemar's test). At the clinically important low end of the EF range (RNEF less than or equal to 35%), 2D-TEE may be expected (with 95% confidence) to be within 15% to +28% EF of reference values, whereas 3D-TEE can be expected to be within 8% to +5% EF relative to RN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868184 TI - Transcutaneous pacing in patients undergoing coronary artery bypass grafting: effect of previous cardiac surgery. AB - Temporary transcutaneous pacing thresholds were measured in 10 patients undergoing primary coronary artery bypass grafting (CABG) operations and 10 patients having reoperative CABG operations 7 months to 14 years after their previous cardiac surgery. All surgeries were performed via median sternotomy. After anesthetic induction using either fentanyl or sufentanil in combination with enflurane, the pacing stimulation thresholds were determined. There was no significant difference (P less than 0.05) between the pacing thresholds of the reoperative group and the primary procedure group (78.2 +/- 6.2 v 79.2 +/- 4.8 mA, respectively). Transcutaneous pacing was successful in all 20 patients. Therefore, transcutaneous pacing thresholds appear unaffected by previous cardiac surgery. PMID- 1868185 TI - A complete regional anesthesia technique for cardiac pacemaker insertion. AB - Sixteen consecutive adult patients scheduled for permanent transvenous cardiac pacemaker insertion received as their total anesthetic the combination of a cervical plexus block and blocks of the second, third, and fourth intercostal nerves using a combination of 1% mepivacaine and 0.2% tetracaine with epinephrine, 1:200,000. This technique consistently provided complete surgical anesthesia of the third cervical (C3) through the fourth thoracic (T4) dermatomes, without anesthesia of the brachial plexus. Anesthesia was adequate for the surgical procedure without the need for supplemental analgesia or anesthesia in all cases. Because fluoroscopy was used routinely for the surgical procedure, it was possible to document that there were no instances of diaphragmatic paralysis or pneumothorax. In contrast to other reports, this technique provides surgical anesthesia that is adequate for all of the approaches used for transvenous pacemaker implantation, except for placement of a battery in an abdominal pouch. There were no serious complications and/or side effects in any of the patients studied. PMID- 1868186 TI - Anesthetic complications during emergency noncardiac surgery in patients with documented cardiac contusions. PMID- 1868187 TI - Diagnosis by transesophageal echocardiography of atrioventricular groove dissection after mitral valve replacement. PMID- 1868188 TI - Advantage of transesophageal over transthoracic echocardiography in the diagnosis of mitral valve endocarditis. PMID- 1868189 TI - Endothelium-derived relaxing factor: basic review and clinical implications. AB - EDRF is a potent, endogenous vasodilator that is produced and released from endothelial cells and subsequently causes the relaxation of VSM through the activation of soluble guanylate cyclase and an increase in VSM cyclic GMP. Structurally, EDRF is likely to be NO or a related nitrogen oxide-containing compound. It is synthesized in endothelial and other cell types from L-arginine by a calcium-calmodulin and NADPH-dependent enzyme. Its action is very similar to the nitrovasodilators that act directly on VSM. EDRF is present in all vascular beds, large and small vessels, and in a wide range of species. Its role in human vascular physiology and pathophysiology is just beginning to be understood. EDRF is a potent endogenous vasodilator and inhibitor of platelet aggregation and adhesion. Its activity is impaired in hypertension and atherosclerosis, and its absence due to endothelial damage may play a role in cerebral and coronary vasospasm. It is a mediator of flow-dependent vasodilation, and its inhibition by hypoxia may contribute to the hypoxic pulmonary vasoconstrictor response. Endothelial cell damage and impairment of EDRF production may also contribute to acute and chronic pulmonary hypertension. A further understanding of the chemical nature and synthetic pathways of EDRF should lead to the production of analogs and antagonists, which may play an important role in future treatments for atherosclerosis, myocardial infarction, angina, hypertension, and other vascular diseases. The recent realization that EDRF serves as the second messenger for guanylate cyclase activation and cyclic GMP production in a variety of cell types outside of the cardiovascular system, including renal and respiratory epithelium, cerebellar neurons, macrophages, and adrenocytes, suggests even broader implications. The importance of EDRF to the anesthesiologist may go beyond an understanding of its role in cardiovascular physiological and pathophysiological states. Initial studies have shown that the endothelium may play a role in mediating the vascular actions of anesthetics, and that anesthetics can inhibit the production, release, or action of EDRF. How are these interactions mediated? Are there significant differences between anesthetics with regard to their effects on EDRF? Is there a clinically significant effect of anesthetics on basal activity of EDRF, or only in response to exogenous stimulation? Conversely, it is important to determine if alterations in endothelial cell function by various disease states such as hypertension, atherosclerosis, adult respiratory distress syndrome, cerebral vasospasm, and others cause changes in the vascular actions of anesthetics. The potential interactions of anesthetics with EDRF production and action in cell types other than the endothelium have not yet been explored.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1868190 TI - Nitrous oxide is contraindicated in patients with coronary artery disease. Pro: nitrous oxide should not be used in patients with coronary artery disease. PMID- 1868191 TI - Nitrous oxide is contraindicated in patients with coronary artery disease. Con: nitrous oxide should be used in patients with coronary artery disease. PMID- 1868192 TI - Sepsis and angiotensin II. PMID- 1868193 TI - Simulation of cardiovascular oxygen balance. PMID- 1868194 TI - A practical setup for temporary pacemakers in cardiac surgery. PMID- 1868195 TI - A gene showing sequence similarity to pectin esterase is specifically expressed in developing pollen of Brassica napus. Sequences in its 5' flanking region are conserved in other pollen-specific promoters. AB - Differential screening of a Brassica napus genomic library led to the isolation of the clone named Bp 19 containing a gene which is highly expressed during microspore development. The accumulation of Bp19 mRNA starts in uninucleate microspores, increases during development reaching a peak in the late stages but declines considerably in mature pollen. The nucleotide sequence of the entire coding region and of extended portions of the 5' and 3' flanking regions was determined. Several homologous cDNA clones were also isolated and sequenced. The Bp 19 gene contains a single intron of 137 bp and gives origin to a mRNA of ca. 1.9 kb which codes for a polypeptide of 584 amino acids. Bp 19 protein has an estimated molecular weight of 63 kilodaltons and has a highly hydrophobic amino terminal region which shows features of a signal peptide. The carboxy half of the Bp 19 protein, starting at amino acid 269, has striking sequence similarity to the pectin esterases of tomato and of the plant pathogen Erwinia chrysanthemi. Four short domains are extremely well conserved in all the three proteins and therefore could represent catalytic sites responsible for enzyme activity. Comparison of the 5' flanking region of the Bp 19 gene with the sequence of other pollen-specific promoters revealed the presence of several conserved regions. These short promoter sequences could correspond to regulatory elements responsible for pollen-specific gene expression. PMID- 1868196 TI - nodT, a positively-acting cultivar specificity determinant controlling nodulation of Trifolium subterraneum by Rhizobium leguminosarum biovar trifolii. AB - Rhizobium leguminosarum biovar trifolii strain TA1 nodulates a range of Trifolium plants including red, white and subterranean clovers. Nitrogen-fixing nodules are promptly initiated on the tap roots of these plants at the site of inoculation. In contrast to these associations, strain TA1 has a 'Nod-' phenotype on a particular cultivar of subterranean clover called Woogenellup (A.H. Gibson, Aust J Agric Sci 19: (1968) 907-918) where it induces rare, poorly developed, slow-to appear and ineffective lateral root nodules. By comparing the nodulation gene region of strain TA1 with that of another R. leguminosarum bv. trifolii strain ANU843, which is capable of efficiently nodulating cv. Woogenellup, we have shown that the nodT gene (B.P. Surin et al., Mol Microbiol 4: (1990) 245-252) is essential for nodulation on cv. Woogenellup. The nodT gene is naturally absent in strain TA1. A cosmid clone spanning the entire nodulation gene region of strain TA1 was capable of conferring nodulation ability to R.l. bv. trifolii strains deleted for nodulation genes, but only on cultivars of subterranean clovers nodulated by strain TA1. This shows that cultivar recognition events are, in part, determined by genes in the nodulation region of strain TA1. Complementation studies also indicated that strain TA1 contains negatively-acting genes located on the Sym plasmid and elsewhere, which specifically block nodulation of cv. Woogenellup. PMID- 1868197 TI - Structural features of the plastid ribosomal RNA operons of two red algae: Antithamnion sp. and Cyanidium caldarium. AB - The nucleotide sequences of the plastid 16S rDNA of the multicellular red alga Antithamnion sp. and the 16S rDNA/23S rDNA intergenic spacers of the plastid DNAs of the unicellular red alga Cyanidium caldarium and of Antithamnion sp. were determined. Sequence comparisons support the idea of a polyphyletic origin of the red algal and the higher-plant chloroplasts. Both spacer regions include the unsplit tRNA(Ile)(GAU) and tRNA(Ala)(UGC) genes and so the plastids of both algae form a homogeneous group with those of chromophytic algae and Cyanophora paradoxa characterized by 'small-sized' rDNA spacers in contrast to green algae and higher plants. Nevertheless, remarkable sequence differences within the rRNA and the tRNA genes give the plastids of Cyanidium caldarium a rather isolated position. PMID- 1868198 TI - Isolation, physical map and gene map of mitochondrial DNA from the cryptomonad Pyrenomonas salina. AB - Mitochondrial DNA (mtDNA) from the cryptomonad Pyrenomonas salina was isolated by CsCl-buoyant density centrifugation of whole-cell DNA in the presence of Hoechst dye 33258. mtDNA consists of circular molecules about 47 kb in size as estimated from restriction enzyme analysis. A physical map for six restriction enzymes (Bam HI, Bge I, Eco RI, Pst I, Sac I and Sal I) has been constructed. Genes coding for the small subunit of rRNA, cytochrome oxidase subunits I and II, and apocytochrome b were localized on this map using Southern blot hybridization with heterologous gene probes from Oenothera. Genes for 5S rRNA and NADH dehydrogenase subunit 5 are absent from P. salina mtDNA. The mitochondrial genome, being the first analysed to this extent in chromophytic algae, should be valuable for taxonomic and phylogenetic studies. PMID- 1868200 TI - Primer extension studies on alpha-amylase mRNAs in barley aleurone. I. Characterization and quantification of the transcripts. AB - Primer extension was used to characterize alpha-amylase mRNAs from aleurone tissue of barley (Hordeum vulgare L. cv. Himalaya) grains. Two synthetic oligonucleotides, specific for the low-pI and high-pI alpha-amylase groups, were used as primers for synthesis of cDNA from total RNA preparations. Between them, these two oligonucleotides appear to account for all major alpha-amylase mRNAs as judged by hybrid-arrested translation of alpha-amylase mRNAs in a cell-free system. Reconstruction experiments indicated that the levels of extended primers (determined by scintillation counting) were directly proportional to the level of input mRNA over a wide range. This indicates that the technique is suitable for quantification of relative levels of individual alpha-amylase from approximately 2% to 100% of maximal levels. The nucleotide sequences of extended primers defined two different alpha-amylase mRNAs in each of the low-pI and high-pI groups, and possibly a third mRNA in the high-pI group. PMID- 1868199 TI - Sequence of the iaa and ipt region of different Agrobacterium tumefaciens biotype III octopine strains: reconstruction of octopine Ti plasmid evolution. AB - The TA regions of biotype III octopine/cucumopine (OC) Ti plasmids are closely related to the TL region of the biotype I octopine Ti plasmids pTiAch5 and pTi15955. Sequence analysis shows that the limited and wide host range biotype III OC TA regions are derived from a common ancestor structure which lacked the 6a gene found in the biotype I octopine TL region. The TA region of the wide host range OC Ti plasmids has conserved most of the original TL-like structure. In most wide host range OC isolates the TA-iaaH gene is inactivated by the insertion of an IS866 element. However, the TA region of the wide host range isolate Hm1 carries an intact TA-iaaH gene. This gene encodes a biologically active product, as shown by root induction tests and indole-3-acetic acid measurements. The limited host range OC Ti plasmids pTiAB3 and pTiAg57 have shorter TA regions which are derived from a wide host range TA region. The AB3 type arose by an IS868-mediated, internal TA region deletion which removed the iaa genes and part of the ipt gene and left a copy of IS868 at the position of the deleted fragment. The pTiAB3 iaa/ipt deletion was followed by insertion of a second IS element, IS869, immediately 3' of the ipt gene. pTiAg57 underwent the same iaa-ipt deletion as pTiAB3, but lacks the IS868 and IS869 elements. Analysis of the various TA region structures provides a detailed insight into the evolution of the biotype III OC strains. PMID- 1868201 TI - Primer extension studies on alpha-amylase mRNAs in barley aleurone. II. Hormonal regulation of expression. AB - Relative levels of different alpha-amylase mRNAs were assessed by primer extension experiments using RNA prepared from aleurone of barley (Hordeum vulgare L. cv. Himalaya). Three different aleurone systems were studied: protoplasts prepared from aleurone layers, isolated aleurone layers, and aleurone from germinated grain. Oligonucleotide primers specific for the low-pI and high-pI alpha-amylase groups allowed the levels of different alpha-amylase mRNAs to be assessed both within and between the two groups. In all aleurone systems the same set of alpha-amylase mRNAs was produced in response to either applied gibberellic acid (aleurone protoplasts, isolated aleurone layers) or, presumably, native gibberellin(s) (germinated grain). This result indicates that the same set of genes is being expressed in each case. Differences were observed between the different aleurone systems in regulation of levels of alpha-amylase mRNAs. In particular, the regulation of alpha-amylase mRNA levels in aleurone of germinated grain has unique features which are not adequately explained by the response of isolated aleurone layers to gibberellic acid. PMID- 1868202 TI - A protein in the oxygen-evolving complex in the chloroplast is associated with symptom expression on tobacco leaves infected with cucumber mosaic virus strain Y. AB - To elucidate the molecular basis of symptom expression in virus-infected plants, the changes in proteins between tobacco, Nicotiana tabacum cv. Ky57, leaves inoculated with cucumber mosaic virus strain Y [CMV(Y)] and strain O [CMV(O)], were compared by 2-dimensional (2-D) gel electrophoresis. The appearance of chlorotic spots in CMV(Y)-inoculated tobacco leaves accompanied an increase of 3 polypeptides and a decrease in 6 polypeptides, as compared with those in the CMV(O)-inoculated tobacco which showed no clear symptoms. The decrease in the amounts of two polypeptides of 22 and 23 kDa was particularly significant: these two polypeptides were compared with a 24 kDa polypeptide, which co-migrated with them in 2-D gel electrophoresis but did not clearly decrease at an early stage of infection, as well as major other proteins of CMV(Y)-inoculated tobacco leaves. However, the 22, 23 and 24 kDa polypeptides showed the same peptide mapping pattern. Furthermore, the 12 amino acid residues at N-termini of the three polypeptides match those of the extrinsic 23 kDa polypeptide of an oxygen evolving complex from spinach. A comparative analysis of the 22, 23 and 24 kDa polypeptides in N. tabacum and its ancestral parents, N. sylvestris and N. tomentosiformis, revealed that the 22 kDa polypeptide derives from N. sylvestris and the 23 kDa polypeptide from N. tomentosiformis; the 24 kDa polypeptide derives from both ancestral Nicotiana species. The results indicate that the polypeptides whose amounts differentially decrease with the progress of symptom expression in N. tabacum inoculated with CMV(Y) are one component of the oxygen evolving complex in photosystem II. PMID- 1868203 TI - Sequence of 18S rDNA of actinorhizal Alnus glutinosa (Betulaceae). AB - The small subunit ribosomal DNA for a woody actinorhizal, Alnus glutinosa, was isolated by the PCR method. Amplification products were cloned into the Bluescript SK- vector. Full sequence, 1698 bp, was obtained with NS1 to NS8 primers. Sequence alignments were made by UWGCG sequence data analysis computer programs. 18S rDNA sequence of A. glutinosa was compared to analogous segments of four other angiosperms, tomato, rice, maize and soybean. Sequence homologies are discussed and application for the technique is suggested. PMID- 1868204 TI - Sequence of Agrobacterium tumefaciens biotype III auxin genes. PMID- 1868205 TI - Molecular cloning of a cDNA from Lupinus polyphyllus cell cultures encoding a ribosomal protein (rps16). PMID- 1868206 TI - Isolation, structure and expression of a cDNA for acetolactate synthase from Brassica napus. PMID- 1868207 TI - Nucleotide sequence of the wheat chloroplast petB and petD genes encoding apocytochrome b-563 and subunit IV of the cytochrome bf complex. PMID- 1868208 TI - Nucleotide sequence of a cDNA clone encoding 23 kDa polypeptide of the oxygen evolving complex of photosystem II in tobacco, Nicotiana tabacum L. PMID- 1868209 TI - The nucleotide sequence of gene 1 of the soybean chalcone synthase multigene family. PMID- 1868210 TI - Fluorescent in situ hybridization to soybean metaphase chromosomes. AB - Repetitive DNA sequences were detected directly on somatic metaphase chromosome spreads from soybean root tips using fluorescent in situ hybridization. Methods to spread the forty small metaphase chromosomes substantially free of cellular material were developed using protoplasts. The specific DNA probe was a 1.05 kb internal fragment of a soybean gene encoding the 18S ribosomal RNA subunit. Two methods of incorporating biotin residues into the probe were compared and detection was accomplished with fluorescein-labeled avidin. The rDNA probe exhibits distinct yellow fluorescent signals on only two of the forty metaphase chromosomes that have been counterstained with propidium iodide. This result agrees with our previous analyses of soybean pachytene chromosomes showing that only chromosome 13 is closely associated with the nucleolus organizer region. Fluorescent in situ hybridization with the rDNA probe was detected on three of the forty-one metaphase chromosomes in plants that are trisomic for chromosome 13. PMID- 1868211 TI - Nucleotide sequence of the chloroplast 16S rRNA gene from pea (Pisum sativum L.). PMID- 1868212 TI - Cloning and nucleotide sequence of a cDNA encoding B-Peru, a regulatory protein of the anthocyanin pathway in maize. PMID- 1868213 TI - Nucleotide sequence of the petA (cytochrome f) gene from the green alga, Chlamydomonas reinhardtii. PMID- 1868214 TI - Nucleotide sequence of Cab-215, a type II gene encoding a photosystem II chlorophyll a/b-binding protein in Pisum. PMID- 1868215 TI - eth1, a gene involved in ethylene synthesis in tomato. PMID- 1868216 TI - Nucleotide sequence of a cDNA encoding a tobacco thioredoxin. PMID- 1868217 TI - Sequence coding for a novel proline-rich protein preferentially expressed in young tomato fruit. PMID- 1868218 TI - A quick method to estimate the T-DNA copy number in transgenic plants at an early stage after transformation, using inverse PCR. AB - Agrobacterium-mediated transformation of plants is known to result in transgenic plants with a variable number of integrated T-DNA copies. Our aim was to obtain transgenic tobacco plants containing one integrated T-DNA copy per genome. Therefore, a quick method was developed to estimate the T-DNA copy number of young transgenic plantlets within 10 weeks after transformation. Inverse polymerase chain reaction (IPCR) was used to amplify junction fragments, i.e. plant genomic DNA sequences flanking the known T-DNA sequences. PMID- 1868219 TI - Sequence of the 5S rRNA gene from Sinapis alba. PMID- 1868220 TI - Nucleotide sequence analysis of a cDNA clone encoding the coat protein gene of peanut stunt virus. PMID- 1868221 TI - Nucleotide sequence of cDNA encoding the precursor of the 23 kDa protein of the photosynthetic oxygen-evolving complex from wheat. PMID- 1868222 TI - Expression of inducible angiosperm promoters in a gymnosperm, Picea glauca (white spruce). AB - Electrical discharge particle acceleration was used to test the transient expression of numerous inducible angiosperm promoters in a gymnosperm Picea glauca (white spruce). Promoter expression was assayed in three different tissues capable of in vitro regeneration, zygotic embryos, seedlings and embryogenic callus. The promoters tested include the light-inducible Arabidopsis and soybean ribulose-1,5-bisphosphate small subunit promoters and a maize phosphoenolpyruvate carboxylase promoter; a soybean heat-shock-inducible promoter, a soybean auxin inducible promoter and a maize alcohol dehydrogenase promoter. Promoters were cloned into a promoter-less expression vector to form a promoter-beta glucuronidase-nopaline synthase 3' fusion. A similar construct was made using the cauliflower mosaic virus 35S (CaMV 35S) promoter as a control. All promoters were expressed in white spruce embryos, yet at levels lower than CaMV 35S. In addition, in the embryos the heat-shock and the alcohol dehydrogenase promoters showed inducible expression when given the proper induction stimulus. In seedlings, expression of all promoters was lower than in the embryos and expression was only inducible with the heat-shock promoter in the cotyledons. Of the tissues tested, the expression level of all promoters was lowest in embryogenic callus. Interestingly, the expression of the beta-glucuronidase gene in embryogenic callus was restricted to the proembryonal head cells regardless of the promoter used. These results clearly demonstrate the use of particle bombardment to test the transient expression of heterologous promoters in organized tissue and the expression of angiosperm promoters in a gymnosperm. PMID- 1868223 TI - Characterization of an ethylene-regulated flower senescence-related gene from carnation. AB - The programmed senescence of carnation (Dianthus caryophyllus L.) petals requires active gene expression and is associated with the expression of several senescence-related mRNAs. Expression of the mRNA represented by the cDNA clone pSR12 has previously been shown to be transcriptionally activated by ethylene specifically in senescing flowers. We report in this paper the structural analysis of this cDNA and its corresponding gene. One cloned genomic DNA fragment, SR12-B, contained the entire transcription unit in 17 exons, interrupted by 16 introns. A second gene, SR12-A, was highly homologous to SR12-B with several nucleotide substitutions and a 489 bp deletion in the 5' flanking DNA sequence. The SR12 transcript has an open reading frame of 2193 bp sufficient to encode a protein of 82.8 kDa. No significant homology at the DNA or protein levels was found with other known genes. We have identified a DNA-binding factor which specifically interacts with two upstream fragments (-149 to -337 and -688 to -1055) of SR12-B. Both fragments apparently compete for the same binding factor. The DNA-binding activity was present in nuclear extracts from both presenescent and senescing carnation petals. The upstream DNA fragments that bind this factor have sequence homology with promoter sequences of other ethylene regulated genes. PMID- 1868224 TI - Production in Escherichia coli of active Sorghum phosphoenolpyruvate carboxylase which can be phosphorylated. AB - Phosphoeolpyruvate carboxylase (PEPC)-deficient mutants of Escherichia coli have been complemented with a plasmid bearing a full-length cDNA encoding the C4-type form of Sorghum leaf PEPC. Transformed cells grew on minimal medium. Two clones were selected which produce a functional and full-sized enzyme protein as determined by activity assays, immunochemical behavior and SDS-PAGE. In addition, regulatory phosphorylation of immunopurified recombinant PEPC was observed when the enzyme was incubated with a partially purified plant PEPC kinase. These results establish that E. coli cells produce a genuine, phosphate-free, higher plant PEPC. Application of immunoadsorbtion chromatography to bacterial extracts makes it possible to prepare highly pure protein available for biochemical studies. PMID- 1868225 TI - Pea lectin is correctly processed, stable and active in leaves of transgenic potato plants. AB - A gene encoding the preproprotein of the pea (Pisum sativum) lectin was expressed in transgenic potato plants using a cauliflower mosaic virus (CaMV) 35S promoter or a tobacco ribulose bisphosphate carboxylase small subunit (ssRubisco) promoter. Presence of the pea lectin to levels greater than 1% of total soluble leaf protein was detected by radioimmunoassay (RIA). The pattern of expression derived from the two promoters was established using both RIA and a squash-blot immunolocalisation technique. Western blotting demonstrated that the preproprotein was correctly processed, generating alpha and beta subunits that assembled to give an isolectin form observed in pea seeds and roots. It was also found that the haemagglutination activity and specificity of pea lectin synthesised in transgenic potato leaves was comparable to purified lectin from pea cotyledons. PMID- 1868226 TI - Isolation of the spinach nitrite reductase gene promoter which confers nitrate inducibility on GUS gene expression in transgenic tobacco. AB - Nitrite reductase is the second enzyme in the nitrate assimilatory pathway. The transcription of this gene is regulated by nitrate as well as a variety of other environmental and developmental factors. Genomic clones containing the entire nitrite reductase gene have been isolated from a spinach genomic library and sequenced. The sequence is identical in the transcribed region to a previously isolated spinach NiR cDNA clone (Back et al., 1988) except for the presence of three introns. The analysis of the genomic clones and DNA blot hybridization demonstrates that there is a single NiR gene per haploid genome in spinach. This is in contrast to what has been found for other plant species. The transcription initiation site has been determined by S1 mapping and the 5' upstream region has been used to regulate the GUS reporter gene in transgenic tobacco plants. This gene was found to be regulated by the addition of nitrate in the transgenic plants. PMID- 1868227 TI - Nursing care of the adult client with infection due to Pneumocystis carinii. AB - Since the beginning of the AIDS epidemic, Pneumocystis carinii pneumonia (PCP) has been the most prevalent opportunistic infection diagnosed in people with AIDS. After a decade of care and research, significant progress has been achieved not only in treating PCP but also in preventing it. Concomitantly, new problems have surfaced, for example, nosocomial spread of mycobacterium tuberculosis and occupational hazards, both related to treating people living with AIDS (PWAs) with PCP. The author provides a comprehensive overview of infection due to Pneumocystis carinii, as seen in adults with HIV infection, and the related nursing issues. PMID- 1868228 TI - Clinical support groups that work. AB - A support group for nurses who care for patients with AIDS has been meeting at a major teaching hospital in New York City for the past year. The authors believe its success has been determined by three components: the group's ability to first, express feelings; second, do a needs assessment and plan programs to meet those needs; and third, participate in the organizational development system of the hospital. Management recognizes the importance of the group, endorses it, and supports it verbally and behaviorally. PMID- 1868229 TI - The view from here. PMID- 1868230 TI - Arguments against mandatory screening for HIV in low-prevalence areas. AB - With heightened awareness that healthcare professionals may be a potential source of infection for the human immunodeficiency virus, calls for serial, mandatory testing and reporting are increasing. Fear and hysteria are particularly noticeable in rural settings, which are only now experiencing marked increases in the incidence of AIDS cases. While arguments for and against the merits of serial mandatory testing programs can be constructed, this paper presents support to oppose mandatory testing. Evidence for this stance is drawn from several sources, including epidemiologic, economic, and clinical research; as well as medical ethics literature. PMID- 1868231 TI - Maximizing aesthetic restorations: the hygienist's role. PMID- 1868232 TI - Dental hygienists and dental implants. PMID- 1868233 TI - Use of the Nd:YAG laser for improved periodontal cosmetics. PMID- 1868234 TI - Combining vital and non-vital tooth whitening: a case sequence. PMID- 1868235 TI - The immediate placement of dental implants into fresh maxillary extraction sites. PMID- 1868236 TI - Aspects of aesthetic smile design. PMID- 1868237 TI - Recurrent deletion in the human antithrombin III gene. AB - Eight unrelated patients with recurrent thromboembolism, a family history of thrombosis, and plasma antithrombin III (ATIII) activity/antigen levels consistent with a diagnosis of heterozygous type I ATIII deficiency were studied by polymerase chain reaction/direct sequencing of ATIII gene exon-coding regions. Frameshift mutations of one base and two bases, respectively, were found to have occurred in two unrelated patients at the same GAG codon (Glu 245) within exon 4 of the ATIII gene. A literature search showed six further hitherto unrecognized deletion "hotspots" in four other human genes. These deletion-prone sites exhibited sufficient sequence homology with each other to derive a consensus sequence (T G A/G A/G G A/C), suggesting that deletion in human genes may not only be non-random but also sequence-directed. PMID- 1868238 TI - Inhibition of human platelet reactivity by endothelium-derived relaxing factor from human umbilical vein endothelial cells in suspension: blockade of aggregation and secretion by an aspirin-insensitive mechanism. AB - To determine a role for endothelium-derived relaxing factor/nitric oxide (EDRF/NO) in regulation of human platelet reactivity by human endothelial cells (EC), we studied combined suspensions of human umbilical vein endothelial cells (HU-VEC, passage 2 through 3) and washed human platelets. Confluent HUVEC monolayers were treated with aspirin (1 mmol/L) to prevent prostacyclin (PGI2) formation, washed, and harvested. Aspirin-treated platelets alone (58 x 10(6)) were fully aggregated by thrombin at 0.05 U/mL or more. In the presence of 10(6) HUVEC, however, platelet serotonin release and aggregation in response to thrombin at doses as high as 0.5 U/mL were blocked. We demonstrated for the first time that inhibition of aggregation and serotonin release, due to EDRF/NO, occurred in parallel. HUVEC-dependent inhibition of platelet responsiveness was enhanced by superoxide dismutase (SOD) and reversed by hemoglobin. The inhibitory effect was also reversed by preincubation of HUVEC with NG-monomethyl-L-arginine (NMA) or NG-nitro-L-arginine (NNA) through competitive blockade of arginine metabolism. Pretreatment of platelets with methylene blue indicated that EC dependent inhibition of platelet reactivity occurred through activation of platelet soluble guanylate cyclase. When platelets and HUVEC were separated by a permeable membrane and both cells were stimulated by thrombin, platelets remained unresponsive. This indicated that inhibition was induced by a fluid-phase mediator, independent of direct cell-cell contact. These data demonstrate that EDRF/NO formation from L-arginine by human EC plays an important role as an aspirin-insensitive fluid-phase inhibitor of human platelet reactivity. PMID- 1868239 TI - Defective lymphokine-activated killer cell generation and activity in acute leukemia patients with active disease. AB - In 26 myeloid and lymphoid acute leukemia patients at presentation the capacity to generate interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) cells effective against the natural killer (NK)-resistant Raji cell line, as well as the susceptibility of the blasts to normal peripheral blood (PB) LAK cells and to autologous LAK effectors was analyzed. The overall PB LAK activity against Raji cells was significantly lower in acute leukemia patients compared with normal controls (mean, 1,473 +/- 971 SD LU/10(8) LAK effectors v 3,340 +/- 1,862; P less than .001). The sensitivity of the blasts to autologous LAK cells was also significantly lower than to normal LAK effectors (517 +/- 593 LU/10(8) LAK effectors v 1,304 +/- 1,066; P less than .01). When the data were analyzed independently, four patterns of behavior could be recognized. The relatively largest group (9 of 26) included patients in whom effective LAK cells could be generated against the Raji line, but in whom the blasts were resistant to autologous PB-LAK effectors while being susceptible to normal LAK cells (defective specific LAK activity). In 5 of 26 cases, an incapacity to generate LAK activity against both allogeneic and autologous target cells was observed (defective LAK generation). In six further cases, the blasts were resistant to both allogeneic and autologous LAK populations, though the latter were effective against the Raji line (resistant blasts). The same defects could also be shown with bone marrow-derived LAK cells. Only in six cases did the leukemic blasts appear susceptible to autologous and allogeneic LAK cells. In four patients the analysis could be repeated at remission, and in three a restoration of the LAK function against the primary blasts was recorded. In the 10 cases studied at relapse, the blasts were resistant to autologous LAK effectors in nine and to normal LAK in seven. These data demonstrate that in most acute leukemia patients with active disease, a defect of the LAK machinery, either a deficient generation of LAK cells or the resistance of the blasts to LAK effectors, may be documented, pointing therefore to a possible contributory role of the LAK system in the control of leukemic cell growth. In view of the frequent normalization of the autologous LAK activity at the time of remission, immunotherapy with IL-2/LAK cells should be primarily aimed to patients with minimal residual disease. PMID- 1868240 TI - Immunolocalization of the Bcl-2 protein within hematopoietic neoplasms. AB - The Bcl-2 proto-oncogene was discovered at the t(14;18) breakpoint found in most follicular B-cell lymphomas and some diffuse large-cell lymphomas. Bcl-2 is unique among proto-oncogenes, being localized to mitochondria and extending cell survival by blocking programmed cell death. We examined Bcl-2 protein expression in 82 hematologic malignancies and reactive lymphoid processes. All lymphomas with Bcl-2 rearrangement demonstrated high levels of Bcl-2 protein. However, most follicular and diffuse lymphomas without Bcl-2 rearrangement also displayed intense Bcl-2 staining. In these cases, mechanisms other than classic translocation may be deregulation Bcl-2. The pattern of Bcl-2 staining in follicular lymphoma is the inverse of the pattern in reactive hyperplasia, confirming a role for Bcl-2 immunolocalization in routine diagnosis. Small lymphocytic malignancies, including small lymphocytic lymphoma, mantle zone lymphoma, and chronic lymphocytic leukemia, expressed intermediate levels of Bcl 2. Bcl-2 protein varied in plasma cell dyscrasias. Bcl-2 protein levels in T-cell lymphomas reflected their corresponding stage of development. No substantial Bcl 2 was present in the Reed-Sternberg cells of nodular sclerosing Hodgkin's disease. Chronic myelogenous leukemia was strongly positive for Bcl-2, consistent with the presence of Bcl-2 in normal myeloid progenitors. Immunohistochemistry identified an expanded spectrum of hematopoietic neoplasms in which Bcl-2 may provide a cell survival advantage. PMID- 1868241 TI - Entire ABL gene is joined with 5'-BCR in some patients with Philadelphia-positive leukemia. AB - In four patients, the chromosome 9 breakpoint of the t(9; 22)(q34;q11) had occurred at different sites within an 8.25-kilobase (kb) region situated 5' of ABL exon 1B. Chromosome in situ hybridization and field inversion gel electrophoresis (FIGE) studies showed that ABL exons 1A and 1B were present on the Ph chromosome. Yet this large fusion gene produced an mRNA conventional for chronic myelogenous leukemia (CML). Splicing from BCR exon 3 to ABL exon 2 crossed more than 200 kb and deleted exons 1A and 1B. This breakpoint site may occur in about 10% of all CML patients. Three of our patients have pronounced thrombocytosis, and two had been diagnosed as having Ph-positive essential thrombocythemia. The platelet count of the other patient was not available. PMID- 1868242 TI - Recombinant human MCP-1/JE induces chemotaxis, calcium flux, and the respiratory burst in human monocytes. AB - The JE gene was first described as a platelet-derived growth factor (PDGF) inducible gene in mouse 3T3 cells. The human homologue of JE encodes a protein whose predicted amino acid sequence is identical to that of the monocyte chemoattractant MCP-1 (also called MCAF and SMC-CF), which belongs to a recently identified family of small secretory proteins with cytokine properties. We purified recombinant human MCP-1/JE (hMCP-1/JE) produced in COS cells and demonstrated that it is chemotactic for human monocytes with a specific activity similar to natural MCP-1. In addition, pure recombinant hMCP-1/JE stimulates monocytes, inducing an increase in cytosolic free calcium and the respiratory burst, but is completely inactive on human neutrophils. These results help to define functionally a well-known growth factor-inducible gene and a member of a new family of cytokines. PMID- 1868243 TI - Sex, gestational age, and weight dependancy of adult hemoglobin concentration in normal newborns. AB - We have measured by cation exchange high pressure liquid chromatography adult hemoglobin (HbA) concentration at birth in 6,123 unselected single newborn individuals. Probably because of the high precision of the analytical method used, we could demonstrate clear a relationship between HbA concentration and, respectively, gestational age and birth weight. We also demonstrated a significant difference in the Hb switching process between male and female newborns. Reference percentile distribution curves are given that could be used to define more precisely those children having slow or fast Hb switching. PMID- 1868244 TI - Correlation of occult clonogenic leukemia drug sensitivity with relapse after autologous bone marrow transplantation. AB - Despite initial complete remission rates exceeding 70%, the majority of patients with acute myeloid leukemia (AML) and adults with acute lymphocytic leukemia (ALL) eventually relapse. Improving the therapeutic results in acute leukemia requires detecting, and understanding the biology of, the minimal residual leukemia remaining after therapy and responsible for relapse. To investigate the biologic relevance of an in vitro assay for clonogenic leukemia (leukemia colony forming units [CFU-L]) as a measure of minimal residual leukemia, we studied 58 consecutive patients with acute leukemia in complete remission undergoing autologous bone marrow transplantation (BMT) with cyclophosphamide-based therapy. CFU-L were cultured from the pretransplant remission marrows in 45 of 58 patients: 35 of 43 patients with AML and 10 of 15 with ALL. Clonal rearrangements, identical to the patients' overt leukemia when available, were detected in the occult CFU-L from four of the eight patients with ALL in whom adequate DNA for analysis could be obtained from the CFU-L. None of the uncultured pretransplant remission marrows from the 15 ALL patients showed clonal gene rearrangements. We also determined the in vitro sensitivity of the occult CFU-L to 4-hydroperoxycyclophosphamide (4HC), and correlated these results with the outcome of the patients. The sensitivity of the occult CFU-L to 4HC was the only factor that predicted relapse following BMT. The actuarial probability of relapse was 18% in the 23 patients whose CFU-L were sensitive to 4HC compared with 77% in the 22 patients whose CFU-L were resistant (P less than .001). The only factor that influenced the CFU-L sensitivity to 4HC was the type of leukemia. The CFU-L from the AML patients were more sensitive to 4HC than the CFU L from the ALL patients (P = .001). Occult CFU-L genetically and functionally represent occult leukemia. Therefore, the CFU-L assay should provide a means for studying the biology of minimal residual leukemia and improving the therapeutic results in patients with acute leukemia. PMID- 1868245 TI - Fetal liver hematopoietic stem cells as a target for in utero retroviral gene transfer. AB - Retroviral-mediated gene transfer into hematopoietic precursors often results in only short-term gene transduction in vivo. Loss of the transduced genetic material over time may be caused by the limited ability of retroviral infection to transduce genes into early, pluripotent hematopoietic stem cells. Because fetal liver contains actively proliferating multipotential stem cells that should be more susceptible to retroviral-mediated gene transfer than quiescent cells derived from adult bone marrow, these cells may be an ideal target for gene transduction. Furthermore, physiologic expansion of these cells during development obviates the need for marrow ablation during gene therapy in vivo. We performed in utero gene transfer by injecting high titer replication-defective retrovirus in vivo into the livers of 11, 14, 16, and 18 day gestation rats. After birth, the rats were analyzed for the presence of proviral integration and gene expression. The efficiency of gene transfer into bone marrow cells was greatest in rats infected at day 14 to 16 of gestation. In rats killed at 1 to 26 weeks of age, gene transfer was detected by Southern analysis in 48% and by polymerase chain reaction in 86% of bone marrow samples. The provirus was also detected in white blood cells, the granulocyte-macrophage colony-forming unit, thymus, spleen, liver, and lung. The presence of the transgene in bone marrow and other hematopoietic tissues at 26 weeks of age suggests that early hematopoietic precursors present in the fetal liver are susceptible targets for gene transfer and that these cells become resident in the bone marrow of the adult animal. This model is a new technique for gene transduction into proliferating hematopoietic cells in vivo that avoids bone marrow transplantation and has potential application in the correction of genetic defects in utero. PMID- 1868246 TI - Graft-versus-host disease prophylaxis with methotrexate/cyclosporine in children with severe aplastic anemia treated with cyclophosphamide and HLA-identical marrow grafts. PMID- 1868247 TI - Administration of erythropoietin to patients with beta-thalassemia intermedia: a preliminary trial. PMID- 1868248 TI - A stop codon in a patient with severe type III von Willebrand disease. PMID- 1868249 TI - The spectrum of genetic defects in a panel of 40 Dutch families with symptomatic protein C deficiency type I: heterogeneity and founder effects. AB - Heterozygosity for protein C deficiency is associated with thromboembolic episodes, but clinical symptoms are nonrandomly distributed among protein C deficient families. This finding has led to the provisional definition of clinically dominant and clinically recessive protein C deficiency. We report here the molecular basis of hereditary, clinically dominant protein C deficiency in a panel of 40 Dutch probands from apparently independent families. All but one subject was a heterozygote for a point mutation in the protein C gene. These 39 subjects shared 15 mutations, six of which occurred in more than one proband (between two and nine). The diversity in the 15 mutations, together with the observation that the most frequent Dutch mutation was also found in a Swedish family with clinically recessive protein C deficiency, makes it unlikely that the molecular basis of protein C deficiency will be different between the clinically dominant and recessive forms. The recurrence of one of the mutations is most likely due to a founder effect, which suggests that when an additional hereditary factor is involved in the clinical severity of protein C deficiency this factor may remain linked to the protein C gene over many generations. PMID- 1868250 TI - Progression and survival studies in early chronic lymphocytic leukemia. AB - To investigate the natural history of stage A chronic lymphocytic leukemia (CLL) we reviewed 84 such patients. Among 74 cases evaluable for disease progression, 22 (29.6%) progressed to more advanced clinical stages (9 to stage B, 13 to stage C); the actuarial estimation of such an event at 4 years was 30% (95% CI: 26.3% to 33.6%). Despite a linear trend toward an increasing risk (r = .92), the hazard function analysis showed a constant pattern of progression, suggesting a lack of correlation of such an event with time (r = .04). Furthermore, disease progression when analyzed as a time-dependent variable had a clear-cut impact on survival (P less than .001). With the aim of identifying a subgroup of patients with low probability of disease progression and death, we applied to our set of patients four different proposals for subclassifying stage A. All methods were similar in terms of sample size, 5-year survival rate, and disease progression risk, suggesting that the choice between different proposals is somewhat arbitrary. Whatever the criteria are for defining "smoldering" CLL, such patients (accounting in the present study for 20.5% of overall series and 46.7% of stage A patients) should not be treated until progression occurs. PMID- 1868251 TI - Phase I trial of recombinant human macrophage colony-stimulating factor in patients with invasive fungal infections. AB - A phase I dose escalation trial of recombinant human macrophage colony stimulating factor (rhM-CSF) in combination with conventional antifungal therapy was conducted in 24 marrow transplant recipients with invasive fungal infection. Daily doses ranged from 100 to 2,000 micrograms/m2/d. Toxicity, such as constitutional symptoms, directly ascribed to rhM-CSF was not observed; however, transient, dose-related thrombocytopenia was observed. Patients who received 2,000 micrograms/m2/d of rhM-CSF had a mean reduction in platelet count of 61,000/mm3 during the rhM-CSF infusion period, which was significant when compared with patients who received lower doses of rhM-CSF (P = .008). Fourteen of the 16 patients who received rhM-CSF after undergoing allogeneic bone marrow transplantation had no change in the severity of graft-versus-host disease (GVHD) while receiving rhM-CSF. One had an increase in the severity of GVHD and one had a decrease. There were no effects on neutrophil, monocyte, or lymphocyte counts. Six patients had resolution of their infections, 12 were not evaluable for response, and six did not respond. Ten patients survived 100 days after initiation of rhM-CSF and 14 died. Further trials with rhM-CSF to assess antifungal activity are indicated. PMID- 1868252 TI - Molecular cloning and in vivo evaluation of canine granulocyte-macrophage colony stimulating factor. AB - Canine granulocyte-macrophage colony-stimulating factor (caGM-CSF) was cloned and expressed to allow further investigation of GM-CSF in a large animal model. The cDNA is 850 base pairs (bp) long and encodes a peptide of 144 amino acids. The nucleotide and amino acid sequence homology between caGM-CSF and human GM-CSF (hGM-CSF) is 80% and 70%, respectively. A mammalian expression vector pCMV/CAGM was constructed and used to transfect COS cells for expression of caGM-CSF. Supernatant from transfected COS cells enriched with caGM-CSF was shown to have significant stimulating activity in granulocyte-macrophage colony forming unit (CFU-GM) assays of canine marrow. caGM-CSF, expressed from bacteria, was used to treat seven dogs at varying doses twice daily subcutaneously (sc) for 14 to 16 days. Circulating blood neutrophils and monocytes increased significantly. The increase in circulating eosinophils was variable. Thrombocytopenia developed during administration of caGM-CSF but corrected rapidly after cessation of treatment. Evaluation of survival times of 51Cr-labeled autologous platelets suggested increased consumption as the primary reason for thrombocytopenia. A species-specific GM-CSF will be a useful tool for hematologic or immunologic studies in dogs. PMID- 1868253 TI - Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha. AB - Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre-IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine. PMID- 1868254 TI - Barrier cells: stromal regulation of hematopoiesis and blood cell release in normal and stressed murine bone marrow. AB - Murine hematopoietic bone marrow is heterogenous in respect to bone-lining cells, hematopoiesis, and release of blood cells. In diaphyseal femoral marrow, bone lining cells are largely osteoblasts, indifferent endosteum, blood cells, and reticular cells. Hematopoiesis is sustained by rather differentiated progenitors, as myelocytes and polychromatophilic erythroblasts. But in sharply restricted loci within trabeculated bone in the distal medial femoral metaphysis, bone lining cells are dominated by newly discovered fibroblastic, contractile, stromal barrier cells; activated, multilaminar and branched, enveloping putative stem cells; and extending into the marrow, where they enclose hematopoietic clusters of rather early progenitors, as promyelocytes; and basophilic erythroblasts. Barrier cells may endocytize granules released individually by vicinal differentiating granulocytes, preventing tissue damage. Barrier cells envelope blood vessels and insinuate processes into their wall, augmenting blood-marrow barriers, preventing release of immature cells. Further, extensions of venous sinuses made of extraordinarily thin barrier cell processes receive released blood cells. With heightened hematopoiesis due to mutant hemolytic anemias or after administration of interleukin-1, barrier cells and their associated structures are greatly increased, spreading beyond normally restricted loci. But in microenvironment-deficient mutants, barrier cells are fewer, less activated, and less granulated. Barrier cells thus appear important in hematopoiesis and in the release of blood cells from bone marrow. PMID- 1868255 TI - Induction of hemoglobin synthesis by downregulation of MYB protein with an antisense oligodeoxynucleotide. AB - Reduced expression of the proto-oncogene c-myb appears necessary for erythroid differentiation induced by chemical agents and by the natural regulator, erythropoietin (Epo). Treatment of Epo-responsive Rauscher erythroleukemia cells with an anti-sense oligodeoxynucleotide to c-myb in the absence of other inducers downregulated myb protein markedly and caused hemoglobinization of the cells within 48 hours. Epo treatment, which downregulates c-myb in these cells, induced hemoglobinization to the same degree. Epo also induced the appearance of anion transport protein on the plasma membrane, consistent with terminal differentiation. In contrast, antisense c-myb did not induce this erythroid marker. The results are consistent with a role for myb protein in the regulation of hemoglobin synthesis. PMID- 1868256 TI - Functional characterization of an abnormal factor XII molecule (F XII Bern). AB - An 18-year-old healthy woman was found to have cross-reacting material (CRM) positive factor XII (F XII) deficiency, F XII clotting activity was less than 0.01 U/mL, whereas F XII antigen was 0.11 U/mL. An F XII inhibitor was excluded. To partially characterize the molecular defect of the abnormal F XII, immunologic and functional studies were performed on the proposita's plasma. The abnormal F XII was a single chain molecule with the same molecular weight (80 Kd) and the same isoelectric points (pl, 5.9 to 6.8) as normal F XII. Dextran sulfate activation of the proposita's plasma showed no proteolytic cleavage of F XII even after 120 minutes, whereas F XII in pooled normal plasma, diluted 1:10 with CRM negative F XII-deficient plasma, was completely cleaved after 40 minutes. Adsorption to kaolin was identical for both abnormal and normal F XII. In the presence of dextran sulfate and exogenous plasma kallikrein, the abnormal F XII was cleaved with the same rate as normal F XII. However, kallikrein-cleaved abnormal F XII was not able to cleave factor XI and plasma prekallikrein, in contrast to activated normal F XII. Thus, these studies show that the functional defect of this abnormal F XII, denoted as F XII Bern, is due to the lack of protease activity of the kallikrein-cleaved molecule. Therefore, the structural defect is likely to be located in the light chain region of F XII, containing the enzymatic active site. PMID- 1868257 TI - Identification of peroxyacetic acid uroporphyrin I in the urine of patients with congenital erythropoietic porphyria by liquid chromatography and mass spectrometry. AB - A new porphyrin, peroxyacetic acid uroporphyrin I, has been isolated from the urine of patients with congenital erythropoietic porphyria by reversed phase high performance liquid chromatography. The porphyrin was characterized by high resolution mass spectrometry and by typical chemical reactions of a peroxyacid. PMID- 1868258 TI - A new method for the determination of adenine phosphoribosyltransferase activity in human erythrocytes by reversed phase high performance liquid chromatography. AB - A new method for the determination of adenine phosphoribosyltransferase (APRT) activity in human erythrocytes is described. APRT activity was assayed by a non radiochemical method in which adenosine monophosphate (AMP) and AMP metabolites produced from a substrate adenine were converted to inosine by alkaline phosphatase and adenosine deaminase. The inosine thus produced was quantitated by reversed phase HPLC. This method was simple, precise, sensitive and free from interference with other co-existing erythrocyte enzymes. Four patients with 2,8 dihydroxyadenine urolithiasis and others with several disorders in purine metabolism have been studied, showing that the present method is clinically useful for the diagnosis and the evaluation of the severity of some human diseases. PMID- 1868259 TI - Characterization of human progesterone receptor by high performance hydrophobic interaction chromatography. AB - High performance hydrophobic interaction chromatography has been used to separate progestin receptors (PRs) from human uterus and from the T47D human breast cancer cell line. Reproducible separations of high resolution were achieved using a TSK Phenyl-5PW column and a reverse salt gradient of 400 mM to 0 mM sodium sulfate in phosphate buffer, pH 7.4. Peaks of radioactivity exhibiting hydrophobic behaviour were isolated, as well as a smaller proportion of specific bound receptors located in the void volume fraction. No differences in retention times were observed between uterine and breast cell line samples. When the technique was used in conjunction with rapid vertical tube sucrose density gradient centrifugation, the 8S sedimenting PR from fresh, low-salt cytosol always eluted with a retention time of 24 min. The natural 4S receptor chromatographed as a single peak at 29 min while the 4S receptor species from high-salt cytosol appeared as two distinct peaks of radioactivity with retention times of 29 and 33 min. While specific binding was shown to occur in the void volume of the column, the origin of these receptors were indeterminate. These results would suggest that under these conditions the 8S receptor occurs as a single hydrophobic class of protein, whereas the data provides evidence that transformed 4S receptor may be proportioned into two unequal entities as a function of exposure to salt. PMID- 1868260 TI - Simultaneous determination of gemfibrozil and its metabolites in plasma and urine by a fully automated high performance liquid chromatographic system. AB - Sensitive and specific methods for the simultaneous determination of gemfibrozil (Lopid), a lipid-lowering agent, and its metabolites in plasma and urine are described. The methods are based on a fully automated high performance liquid chromatographic (HPLC) system with fluorescence detection. Urine samples, diluted with acetonitrile, were directly analysed by HPLC using a flow and eluent programming method. In the case of plasma, gemfibrozil and its main metabolites were extracted from acidified samples and the resulting extracts injected into the chromatographic system. The sensitivity was approximately 100 ng/mL for gemfibrozil and its four metabolites using 0.5 mL plasma or urine. An acyl glucuronide of gemfibrozil excreted in human urine after oral administration of the drug was isolated and its structure and stability examined. PMID- 1868261 TI - Direct enantiomeric high performance liquid chromatographic separation of aminoglutethimide and its major metabolite on a series of Chiralcel OD and Chiralcel OJ columns and its application to biological fluids. AB - A direct, isocratic, sensitive and precise liquid chromatographic method is presented for the enantiomeric separation of aminoglutethimide (AG) and its acetylated metabolite (AcAG) using cellulose tris-3,5-dimethyl phenyl carbamate (Chiralcel OD) and cellulose tris(4-methylphenyl benzoate) ester (Chiralcel OJ) columns in series. The enantiomeric elution order is determined by separate chromatography of the racemate AG and racemate AcAG and of their separate enantiomers under similar conditions. This method has been used to determine and identify the enantiomers of AG and AcAG in the urine sample collected from a metastatic breast cancer patient after administration of AG for 24 h. Large amounts of (+)-R-AG are excreted unchanged in the urine together with smaller quantities of (+)-R-AcAG, while most of the (-)-S-AG is metabolically converted into (-)-S-AcAG. PMID- 1868262 TI - A reversed phase liquid chromatographic method for the simultaneous determination of several common penicillins in human serum. AB - A rapid and sensitive high performance liquid chromatographic method is described for the simultaneous determination of benzylpenicillin, ampicillin, phenoxymethylpenicillin, cloxacillin, dicloxacillin and nafcillin in small samples of human serum. The chromatographic system involves the use of a Spherisorb ODS reversed phase column and a gradient elution with 1 mM ammonium acetate buffer/acetonitrile (from 90:10 to 75:25 in 15 min). Detection and quantification are monitored by UV absorption at 208 nm. The compounds are extracted with dichloromethane, using tetrabutylammonium hydrogen sulfate neutralized with sodium hydroxide and buffered with borate as an ion pairing reagent; beta-hydroxyethyltheophylline is added as an internal standard. Our results show that the method is accurate and reproducible, allowing quantification of serum levels of assayed penicillins (0.5-50 micrograms/mL) without interference from other drugs commonly used in therapy. Recoveries were generally greater than 79.4%. PMID- 1868263 TI - Separation of beta- and gamma-tocopherols in serum by high performance liquid chromatography. AB - A simple and sensitive high performance liquid chromatographic method for the analysis of tocopherols (alpha, beta, gamma and delta) in serum with UV detection is described. In normal phase mode excellent separation of positional isomers (beta and gamma) was achieved by adjusting the proportion of isopropanol in the mobile phase. Detection limits for both beta and gamma were 0.62 mg/L and 0.42 and 1.2 mg/L for alpha and delta isomers, respectively. Measurement of all the tocopherol structural isomers (alpha, beta, gamma and delta) in a sample required only 400 microL of serum and each run was completed in less than 22 min. PMID- 1868264 TI - Separation of proteins by consecutive sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and reversed phase high performance liquid chromatography. AB - A procedure for the preparative separation of proteins was developed by using consecutively sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (SDS-PAGE) and reversed phase high performance liquid chromatography (HPLC). The proteins were separated by SDS-PAGE and afterwards extracted from the gel. The extracted proteins were separated from SDS and other small molecular weight contaminants on a Fractogel TSK HW-40 (F) column in acidic aqueous acetonitrile. The proteins eluted from the Fractogel column were fractionated by HPLC. The identity and purity of the recovered proteins was confirmed by SDS-PAGE analysis. PMID- 1868265 TI - Inorganic supports coated with N-substituted polyacrylamides: application to biospecific chromatography of proteins. AB - Wide porous glass (WPG) chemically coated with a poly-N-(2 hydroxyethyl)acrylamide layer is proposed as a carrier of biospecific ligands in affinity chromatography. The method of WPG chemical modification includes synthesis of the gamma-aminopropyl derivative followed by chemical adsorption of poly(p-nitrophenyl acrylate). Ester groups of the polyacrylate-coated WPG can be used for coupling the ligands bearing primary amino groups. Condensation of esters with ethanolamine yields a poly-N-(2-hydroxyethyl)acrylamide-coated support with non-specific adsorption properties resembling those of Sepharose 4B. Human IgG immobilized on the polyacrylate support was used for isolation of the first complement component from human serum and for its separation into subcomponents C1r, C1s and C1q by a one-step method. An unbound part of serum may be used as the R1 reagent for determining haemolytic C1 activity. The stepwise elution of C1r, C1s and C1q from the column reflects the course of C1 breakdown after its activation on immune complex formation. PMID- 1868266 TI - Rapid determination by high performance liquid chromatography of di-2-ethylhexyl phthalate in plasma stored in plastic bags. AB - A rapid sensitive technique was developed for the analysis of di-2-ethylhexyl phthalate (DEHP) in plasma stored in plastic bags by using high performance liquid chromatography (HPLC) with UV detection and a Hypersil ODS column. The compound was easily and efficiently extracted with a mixture of sodium hydroxide and acetonitrile, which allowed the deproteinization of plasma samples. The recovery was greater than 95% and the intra- and inter-assay coefficients of variation were better than 6.5%. The results obtained showed that the amount of DEHP accumulated in plasma varied according to different parameters and depended on the storage conditions (time, temperature and shaking) and also on the lipid content of the stored plasma and the sterilization process of the PVC bags. PMID- 1868267 TI - Initiation and progression of mineralization of bone nodules formed in vitro: the role of alkaline phosphatase and organic phosphate. AB - Osteoid nodules form but do not mineralize in fetal rat calvaria cell cultures grown in alpha-minimal essential medium with 10% fetal bovine serum in the absence of Na beta-glycerophosphate (beta-GP). To study factors involved in the initiation and progression of mineralization, cultures were treated with beta-GP and radiolabelled with 0.1-0.2 microCi/ml 45Ca after nodules had formed (17-19 days in medium without beta-GP). Concentrations of beta-GP from 1 to 14 mM induced a dose-dependent increase in 45Ca uptake. 45Ca uptake was restricted to nodule-containing cultures and did not occur in cultures without nodules. Continuous labelling over 72 h compared with 2 h pulses over the same time period showed that little mineralization occurred over the first 8-12 h and that the rate of mineralization was maximal and constant after 24 h exposure to beta-GP. Calcium uptake from medium was slow during the first 12 h of beta-GP exposure but increased rapidly thereafter until the medium calcium concentration reached a steady state of between 0.5 and 0.6 mM. Measurement of calcium concentration in the medium after mineralization had been initiated (24 h after beta-GP exposure) showed a linear calcium uptake into nodules (r = 0.990) over a 7 h period at a rate of 9.2 micrograms calcium/h/culture. Initiation of mineralization was prevented by 100 microM levamisole, but not by 100 microM dexamisole. When 100 microM levamisole was added 24 h after mineralization had been initiated by the addition of beta-GP, the progression of mineralization was unaffected. Similarly, after mineralization had been initiated for 24 h by 10 mM beta-GP, mineralization continued independent of the presence of beta-GP. The data show that the initiation and progression of mineralization are separate phenomena and that organic phosphate and alkaline phosphatase play a crucial role in the initiation of mineralization but are not required for the continuation of mineralization of bone nodules. PMID- 1868268 TI - Mineralized nodule formation in rat bone marrow stromal cell culture without beta glycerophosphate. AB - Rat bone marrow stromal cells were cultured in the presence of 10 nM dexamethasone and various concentrations of beta-glycerophosphate. At day 12-15, some nodules consisting of polygonal cells were formed in all culture conditions, and these nodules were mineralized 2-3 days later. beta-Glycerophosphate significantly enhanced nodule formation at concentrations of not less than 5 mM. The mineralized nodules formed in the absence of beta-glycerophosphate were examined using phase-contrast microscopy, undemineralized and demineralized tissue histology, histochemistry for alkaline phosphatase, immunohistochemistry for type I, II, and III collagen, energy dispersive X-ray microanalysis, electron diffraction, and Fourier transform infrared spectroscopy (FT-IR). Mineralized nodules had histological characteristic similar to bone. Cells associated with nodules exhibited high alkaline phosphatase activity, and extracellular matrix of the nodules predominantly consisted of type I collagen. X-Ray microanalysis showed the presence of Ca and P in the mineralized area, and electron diffraction pattern showed the mineral to have apatite crystal structure. Moreover FT-IR indicated that the mineral was a mixture of hydroxyapatite and carbonateapatite. From these observations, it is concluded that the mineralized nodules formed in our culture system are truly bone-like. PMID- 1868269 TI - Binding of serum osteocalcin to hydroxyapatite in Paget's disease of bone. AB - Serum osteocalcin (serum bone Gla protein, sBGP) is elevated in diseases characterized by an enhanced bone turnover. However, in Paget's disease of bone there is a discrepancy between the low increase of sBGP and the high increase of bone remodelling assessed by serum alkaline phosphatase and urinary hydroxyproline. It is possible that the relatively low levels of sBGP reflect an abnormal binding of the molecule to the bone due to an alteration of the BGP molecule and/or of the pagetic mineral phase of bone. Another possibility would be a disregulation of BGP synthesis. In the present work we studied the binding of pagetic sBGP to an experimental model of mineral phase of bone (HPLC hydroxyapatite column). Serum of 14 patients with Paget's disease of bone (sBGP = 7.8 +/- 3.5 ng/ml) and of 14 control subjects (sBGP = 3.3 +/- 0.9 ng/ml) was purified through a Sephadex G-50 medium column (2.6 x 100 cm, 5 mM NH4CO3H). The BGP peak was lyophilized and resuspended in 1 mM KH2PO4, 1 mM CaCl2, 0.02% NaN3, pH 8.4, and then injected into an HPLC gradient system (Waters 660), from 1 to 300 mM KH2PO4 through a hydroxyapatite column (BioGel HPHT, Bio-Rad, 0.78 x 10 cm). A single peak of sBGP was obtained with a retention time of 12 min in control and pagetic patients. From these results we conclude that BGP binding to hydroxyapatite is similar in pagetic patients and in control subjects, suggesting that an alteration in BGP molecule is not responsible for an abnormal binding to the bone. In order to validate our system, the binding of serum BGP from warfarin treated rats to the hydroxyapatite HPLC column was also studied and compared to binding of serum BGP from normal rats. PMID- 1868271 TI - [Register of the Royal Academy of Medicine and program of meetings]. PMID- 1868270 TI - Bone densitometric and histomorphometric responses to sequential human parathyroid hormone (1-38) and salmon calcitonin in osteoporotic patients. AB - Cyclical treatments of osteoporosis utilizing a skeletal Activator of bone remodelling, and sequential therapy with a Depressor to selectively block the resulting phase of osteoclastic resorption have been dubbed 'ADFR' therapy; there is usually a treatment Free interval while the activated bone multicellular units complete the remodelling cycle before the protocol is Repeated. In this report an ADFR protocol was developed in which all patients received synthetic hPTH (1-38) for the first 14 days of a 100 day cycle. Half the patients received no other therapy (Group 1), but were followed closely with repeated vertebral bone mineral measurements over two full cycles. The remaining patients (Group 2) were randomly allocated to receive salmon calcitonin, at an average dose of 79 units per day for a 56 day depressor period immediately following each phase of activation. Detailed bone histomorphometry was performed on iliac biopsies obtained before treatment and at the end of the second cycle (Day 200). In Group 1, the serum alkaline phosphatase (Alk. P'ase) increased by 23 +/- 12% (P less than 0.01) and by 18 +/- 16% (P less than 0.03) of the baseline values following PTH treatment during the first and second cycles, respectively. The overall changes in serum Alk. P'ase across time were significantly less (P less than 0.04) in Group 2; however this parameter also increased by 15 +/- 15% during the first cycle and 8 +/- 6% during the second cycle. Vertebral BMC increased by 13% in Group I (P less than 0.01), but forearm BMC decreased by 11% (P less than 0.05) over the two cycles of therapy. There were no significant changes in bone mineral measurements in Group 2, but the differences between the two groups were not significant. Eighteen paired biopsies were available for histomorphometric analysis. There were no significant changes in static parameters measuring total bone tissue, osteoclastic function or osteoid formation after two cycles of treatment. Individual bone formation rates (surface referent) were not significantly different between the two groups; the pooled data for all biopsies showed a small but insignificant increase from 0.030 +/- 0.018 to 0.035 +/- 0.028 mm3/mm2/day. However there was a significant increase in the activation frequency (the probability of a remodelling event occurring on queiscent cancellous surface) from 13 +/- 7 to 27 +/- 26/day x 10(-4) (P less than 0.05) when calculated for the pooled data from both groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1868272 TI - Tribute to Vivian Chang, M.D. PMID- 1868273 TI - Drug abuse: a national policy perspective. PMID- 1868275 TI - Scientific foundation of clinical practice: opiate use in pregnant women. PMID- 1868274 TI - Clinical implications of recent research on the fetal alcohol syndrome. PMID- 1868277 TI - Preventive strategies in education: history, current practices, and future trends regarding substance abuse and pregnancy prevention. PMID- 1868276 TI - Perinatal effects of cocaine and amphetamine use during pregnancy. PMID- 1868278 TI - Detoxification considerations in the medical management of substance abuse in pregnancy. PMID- 1868279 TI - Residential therapeutic communities for female substance abusers. AB - Therapeutic communities provide a unique model for the needs of chemically dependent mothers who are pregnant or of child bearing age. These programs have been treating female addicts, many of whom reflect the profile and needs of the current generation of addicted mothers in clinical problems, social disadvantages, and poor socialization. Specific issues of their recovery can be most efficiently addressed in a residential community that provides housing and a comprehensive approach including medical, social, psychological care, parental training, and child care. Most evident is that these women need a lifestyle change, an opportunity for maturation. In this regard, the therapeutic community offers the essential element of community as a setting for learning right living. PMID- 1868280 TI - Working with pregnant women at high risk for HIV infection: outreach and intervention. PMID- 1868281 TI - Planning for future actions. Workshop on public policy considerations. PMID- 1868282 TI - Planning for future actions. Workshop on education and outreach initiatives. PMID- 1868283 TI - Planning for future actions. Workshop on detoxification policies and directions. PMID- 1868284 TI - Planning for future actions. Workshop on residential and outpatient treatment modalities. PMID- 1868285 TI - Implications for New York State policy. PMID- 1868286 TI - Statement on preserving New York City's drinking water quality and protecting public health. Committee on Public Health. PMID- 1868287 TI - Regulation of residency training. PMID- 1868288 TI - The impact and practical aspects of the implementation of the new working conditions for residents in the Department of Obstetrics and Gynecology at the Albert Einstein College of Medicine. PMID- 1868289 TI - A surgical program. Director's view. AB - In summary, the two major facts that have emerged from a year and a half of experience with 405 regulations are shown in Table VI. The increased staffing with the monies made available has greatly enhanced patient care and decreased the resident workload. I want to again compliment Dr. Axelrod for the foresight to make these funds available despite adverse criticism. He clearly understood that the changes needed were quite expensive because the problems are primarily economic in origin. What type of paramedical personnel are needed is yet uncertain. I mentioned briefly earlier that the "data manager" combines an excellent administrative secretary and a nurse. The simple institution of electronic data processing can, surprisingly enough, worsen the problem rather than help. For example, institution of a beeper system, making it possible for anyone to "beep" a house officer at any time, resulted in an astonishing increase in "beeper frequency," a house officer receiving seven or eight such messages per hour, 24 hours a day, rather than communicating by other methods. Such "instant" communication can become a serious hazard rather than a help. Second, as repeatedly mentioned, the on-call time concept is crucial, permitting flexibility that avoids fatigue and yet maintains continuity of care. Otherwise there is a real danger with a rigid time-on/time-off schedule. PMID- 1868290 TI - The effects of residency regulation: a program director's view. PMID- 1868291 TI - State residency regulation: a view from out of state. PMID- 1868292 TI - Professional responsibility: a perspective on the Bell Commission reforms. PMID- 1868293 TI - The effects on residents' experience: the view of the surgical resident. PMID- 1868294 TI - Professionalism and residency reform. PMID- 1868295 TI - Institutional perspectives on residency regulation: a dean's view. PMID- 1868296 TI - Where do we go from here? PMID- 1868297 TI - Prospects for the future. PMID- 1868298 TI - Over my dead body: coroner's case. PMID- 1868299 TI - Ventouse or forceps? PMID- 1868300 TI - Overwhelming demand for breast screening. PMID- 1868301 TI - Running addiction. PMID- 1868302 TI - Unravelling the causes of Alzheimer's disease. PMID- 1868303 TI - Placental alkaline phosphatase in seminoma. PMID- 1868304 TI - POEMS syndrome: further investigations of an unusual case. PMID- 1868305 TI - Mitochondrial disease and mitochondrial DNA. AB - In the last decade there have been dramatic advances in the understanding of genetic, biochemical and clinical aspects of disorders of the mitochondrial respiratory chain. Neurological manifestations are prominent although involvement of other systems is increasingly recognized. This article reviews current understanding of mitochondrial disease and in particular its genetic basis. PMID- 1868306 TI - Prosthetic valve endocarditis. AB - Prosthetic valve endocarditis occurs in 2-4% of patients with prosthetic valves and carries a mortality of around 50%. A low index of suspicion should enable early diagnosis. The empirical use of antibiotics in patients with a prosthetic valve who develop an unexplained fever is inappropriate. Careful liaison between cardiologist, microbiologist and cardiac surgeon is essential for optimal management. PMID- 1868307 TI - Antenatal assessment of intrauterine growth retardation. AB - Intrauterine growth retardation is associated with considerable fetal mortality and morbidity. The condition often appears unexpectedly and the various clinical and ultrasound strategies used to screen for it in pregnancy have given disappointing results. Once intrauterine growth retardation is suspected, methods to evaluate the fetus are generally satisfactory provided they are applied systematically. PMID- 1868308 TI - Possible significance of familial aggregations of multiple sclerosis. AB - More than 150 years after multiple sclerosis (MS) was first described, its cause remains unknown. In defining the aetiology of MS the question of the relative importance of genetic and environmental factors in the development of the disease is crucial. Familial clustering of cases strongly supports the hypothesis that genetic factors are fundamental in determining disease susceptibility. PMID- 1868309 TI - Psoriasis and calcipotriol. PMID- 1868310 TI - Psychological treatment superior in bulimia nervosa. PMID- 1868312 TI - Why do GPs overprescribe antibiotics? PMID- 1868311 TI - Behavioural toxicity of antidepressants. PMID- 1868313 TI - Identification of the epidural space. PMID- 1868314 TI - Junior doctors and market forces. PMID- 1868315 TI - Resting behaviour of cattle in a slaughterhouse lairage. AB - One-hundred and thirty-five groups of cattle were observed in a slaughterhouse lairage. Groups of cattle that arrived direct from farms took longer to lie down and spent less time lying down than those that arrived from markets. In 72 groups, the majority of time was spent with no animals in the group lying down. In only 42 groups was the majority of the time spent with greater than one-half of the group lying down. In 97 groups, over three-quarters of the time in the lairage was spent with no cattle in the group moving. The proportion of time that cattle spent moving and lying down was also affected by the sexual composition of the group and also by group size. In cattle direct from farms, moving behaviour was greater in groups containing cattle with horns than in similar groups that did not contain cattle with horns. PMID- 1868316 TI - Some preslaughter factors affecting the occurrence of bruising in sheep. AB - The preslaughter handling and behaviour, and subsequent bruising was observed in 49 groups of sheep in a commercial slaughterhouse. A greater percentage of bruised carcases was found in lambs (71%) than in ewes (49%) (P less than 0.01). A greater percentage of severely bruised carcases was found in lambs from markets (20%) than in those direct from farms (12%) (P less than 0.05). Significant correlations were found between the occurrence of recent bruising and wool-pulls during unloading, riding by another sheep, and hits and squashes against structures at the slaughterhouse. However, even assuming that each potentially traumatic event observed in the slaughterhouse caused a bruise, only about one quarter of the bruising could have been attributed to handling problems at the slaughterhouse. Eight-eight per cent of all bruises were estimated to have been caused within about 24 h of death, indicating that most bruising probably was caused by handling problems during loading on the farm, during transit and particularly at markets. PMID- 1868317 TI - Pathogenicity of different species of staphylococci in caprine udder. AB - Aseptic foremilk samples were collected from Finnish landrace goats. Ten different species of staphylococci, causing subclinical infections were detected. Twelve goats with persistent subclinical staphylococcal infection were followed on a monthly basis and compared with foremilk samples of nine goats suffering from clinical mastitis. Parameters of inflammation based on the activity of the California Mastitis Test (CMT). N-acetyl-beta-D-glucosaminidase (NAGase) and antitrypsin were determined from the milk. Staphylococci were further classified using the API STAPH system. On the basis of elevations of activities of CMT, NAGase and antitrypsin, Staphylococcus aureus was the most pathogenic in clinical and subclinical mastitis, S. hyicus showed only marginal pathogenicity. Subclinical infections were persistent and the infective organism was not always detected from milk by culture. The biochemical reactions of subclinical staphylococci seemed to vary within the same gland by time. Antitrypsin was most effective in differentiating between subclinical and clinical infection. A teat cistern puncture technique was found to be suitable for the goat. PMID- 1868318 TI - Microscopic changes in infected bovine teats. AB - Two hundred and fifty-two teats from the udder quarters of 68 dairy cows were studied by bacteriological examination of quarter milk samples and microscopic examination of the teats. Of 252 quarters, 169 teats showed inflammatory changes, while 83 were of normal appearance. The inflammatory changes consisted of either neutrophil infiltrations, mononuclear cell infiltrations and fibrosis, or a combination of these changes. The reaction was restricted to the teat cisterns and/or Furstenberg's rosettes, but very rarely also in the teat canal. In 136 of 169 cases, the inflammatory reaction was associated with bacteria in the milk, while in 33 cases no bacteria could be recovered from milk, in spite of inflammatory changes in the teat structures. Only 36 of 83 of normal teats were bacteriologically positive. PMID- 1868319 TI - Scrapie in Cyprus. AB - Scrapie was first recorded in Cyprus in 1985 in two flocks of sheep and subsequently the disease was diagnosed in dairy goats kept in mixed flocks with affected sheep. By 1989 scrapie had been diagnosed in 23 flocks. Epidemiological data presented in the present study are essentially from clinicopathological investigations between 1985 and 1989. A total of 356 out of 957 sheep and 10 out of 30 goats examined from flocks in Nicosia, Larnaca and Limassol districts showed histopathological lesions consistent with a diagnosis of scrapie. PMID- 1868320 TI - Diminazene aceturate residues in the tissues of healthy, Trypanosoma congolense and Trypanosoma brucei brucei infected dogs. AB - The tissue distribution and residue profile of diminazene aceturate was investigated in healthy dogs and in dogs infected with Trypanosoma congolense and Trypanosoma brucei brucei. The drug was administered at 3.5 mg/kg i.m. and tissue samples were taken post mortem from the animals at 48, 72, 120, 168 and 240 h after injection. The drug was distributed to various organs and tissues of the body with the highest concentrations occurring in liver and kidney. Higher drug levels were obtained in the tissues of healthy dogs compared with trypanosome infected animals except in the brain. The levels of residues in the healthy animals were significantly different (P less than 0.05) from those of the infected dogs. The drug residues were still detectable in the tissues of the animals 10 days after drug administration. PMID- 1868321 TI - Osmotic fragility of erythrocytes of west African dwarf sheep and goats: effects of temperature and pH. AB - The osmotic fragility of erythrocytes of West African Dwarf (WAD) goats and of WAD sheep was determined at different temperatures and pH. Erythrocytes of the goats were more susceptible to osmotic haemolysis than those of the sheep. However, the osmotic fragility of erythrocytes of both species increased with a decrease in temperature or pH. PMID- 1868322 TI - The value of progesterone, oestradiol benzoate and cloprostenol in controlling the timing of oestrus and ovulation in dairy cows and allowing successful fixed time insemination. AB - The relative merits of three hormone treatments of dairy cows: (1) intravaginally administered progesterone and oestradiol benzoate; (2) intravaginally administered progesterone and injected cloprostenol; and (3) injected cloprostenol; begun 35-75 days after calving and designed to synchronize oestrus and ovulation and allow successful artificial insemination (AI) at fixed times, have been assessed utilizing information from progesterone concentrations in milk. From this it was concluded that 89% of the cows had ovulated one to three times between calving and the beginning of treatment. Treatment (2) was more effective than (1) in synchronizing ovulation. This was due to the fact that when treatments began early in the ovulation cycle, the requirement for a rapidly effective luteolytic agent was provided by cloprostenol but not by oestradiol benzoate. Treatment (2) was also more effective than (3) in synchronizing ovulation. This is interpreted as meaning that progesterone treatment for 12 days had a beneficial effect in restoring normal cyclic ovarian function in the cows after calving. Whilst cloprostenol administered alone did not have this beneficial effect, there is no evidence that it had a detrimental effect. Based on all cows in treatment groups, the proportion that became pregnant to the fixed time AI was significantly greater after treatment (2) than after (1), but when based on numbers of cows with synchronized ovulation, there were no significant differences among treatments in the proportions becoming pregnant. The progesterone/cloprostenol treatment had a disadvantage in that when begun during the 11-22 day period of the ovulation cycle, so resulting in a long, total period of suppression of ovulation (mean, 32.1 days), fertility to the fixed-time AI was poor despite effective synchronization of ovulation. Ovulation cycles immediately following the failed, fixed-time AI were normal, both in length and in maximum, luteal-phase progesterone concentration and indicated normal corpus luteum function. Thus the infertility could be ascribed neither to poor timing of AI nor to gross degeneration of follicles prior to their synchronized ovulation following the prolonged suppression of ovulation. The 12-day progesterone treatments when given to anovulatory cows gave, within 5.5 h of their beginning, a concentration of progesterone in milk that was not significantly different from the maximum reached. This concentration declined during the 12 days of the treatment but remained above pretreatment level until 5.5 h after treatment withdrawal; the maximum reached was about half that in normal ovulation cycles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1868323 TI - Two hundred years of veterinary education: lessons and reminiscences from the history of the Royal Veterinary College. PMID- 1868324 TI - Pharmacodynamics and pharmacokinetics of miloxicam in the horse. AB - The novel non-steroidal anti-inflammatory drug (NSAID) miloxicam was administered intravenously to six New Forest ponies at a dosage rate of 0.6 mg/kg in a two part cross-over study. In each part, three horses received miloxicam and three were given a placebo preparation. The actions of miloxicam, compared to placebo, were assessed in a carrageenan-sponge model of acute inflammation. The rise in skin temperature over the site of the acute inflammatory reaction was less in treated ponies, but differences were not statistically significant. Concentrations of the enzymes acid phosphatase (AP) and lysozyme in inflammatory exudates harvested at 4, 8, 12 and 24 h were not significantly different in drug treated animals compared with those receiving placebo. Concentrations of protein and lactate dehydrogenase (LDH) in exudate and exudate leucocyte numbers were significantly reduced in drug-treated horses when data for all sampling times were pooled. The differences were not significant, however, at each sampling time. Exudate concentrations of the eicosanoids, bicyclic-PGE2, 6-keto-PGF1 alpha and TXB2, were reduced significantly by miloxicam at most sampling times, and serum TXB2 was also significantly reduced at 4 and 8 h but not at 12 and 24 h after drug administration. These pharmacodynamic findings correlated with the pharmacokinetic properties of miloxicam. The plasma concentration-time curve was defined by a three-compartment open model in one pony and by a two-compartment model in five ponies. Mean values for pharmacokinetic parameters for the five ponies were: t1/2 alpha 0.40 h; t1/2 beta 2.70 h; Vd area 0.158 l/kg; ClB 41.87 ml/kg/h. Exudate concentrations of miloxicam were initially similar to and eventually greater than concentrations in plasma, and this may explain the more prolonged inhibition of eicosanoid synthesis in exudate than in serum. These findings demonstrate the value of relating, in a single experimental study, drug action on a range of variables to drug fate in the body. PMID- 1868325 TI - Sulfhydryl reducing agents distinguish two subtypes of angiotensin II receptors in the rat brain. AB - Two angiotensin II receptor subtypes were distinguished in the rat brain using in vitro receptor autoradiography based on the differential effects of sulfhydryl reducing agents on 125I-sarcosine1,isoleucine8 angiotensin II binding in various brain nuclei. At several nuclei, e.g. the hypothalamus, circumventricular organs and the dorsal medulla, 125I-sarcosine1,isoleucine8 angiotensin II binding was strongly inhibited by 30 mM beta-mercaptoethanol or 5 mM dithiothreitol, whereas at other nuclei, e.g. the lateral septum, colliculi, locus coeruleus and medial amygdala, sulfhydryl reducing agents had either little effect on radioligand binding or enhanced the binding. The distribution of the sulfhydryl reducing agent inactivated subtype corresponds exactly with the distribution of DuP 753 sensitive (designated as AII alpha) 125I-sarcosine1,isoleucine8 angiotensin II binding sites25. The subtype not inhibited by sulfhydryl reducing agents corresponds with the DuP 753 insensitive (designated as AII beta) sites in the brain25. The sulfhydryl reducing agent effect on brain angiotensin II receptor subtypes is similar to that seen in angiotensin II receptor subtypes in peripheral tissues. These observations indicate that many previous studies of brain angiotensin II receptor binding that included 5 mM dithiothreitol in the assay medium overlooked the sulfhydryl reducing agent inactivated (AII alpha) receptor subtype. PMID- 1868326 TI - Reversible, short-lasting, and dose-dependent effect of (+)-fenfluramine on neocortical serotonergic axons. AB - Dextrofenfluramine [+)-fenfluramine) is the dextro-optical isomer of the racemic compound (+/-)-fenfluramine. This compound stimulates the release of serotonin (5 HT) and blocks its re-uptake in serotonergic nerve terminals. (+)-Fenfluramine and its nor metabolite which have been localized in significant amounts in the rat brain are useful anorectic agents in animals. In humans, (+)-fenfluramine is used as an anti-obesity agent when administered orally in doses of 0.25 mg/kg/twice a day. Studies in some animal species (such as the rat and monkey, but not mice) using high doses of (+)-fenfluramine (administered subcutaneously) have shown long-term neurochemical and immunocytochemical effects in selected brain regions. In the present study we used the rat to determine the mechanism underlying the anorectic effect of orally administered (+)-fenfluramine. The rat was selected because long-term effects of (+)-fenfluramine have been previously described in this species. In addition, a variety of other aspects of orally administered (+)-fenfluramine have been addressed in this study. For example, how long does the depletion of 5-HT in the nerve terminals last following cessation of the drug treatment? i.e. is the effect reversible? Is this depletion of 5-HT and the resultant abnormal morphology of 5-HT-immunoreactive nerve terminals seen at high doses dose-dependent? Since some of these questions relate to morphological evaluation of this drug in brain 5-HT systems, we have examined this system as part of our ongoing effort to examine brain monoaminergic systems under perturbed conditions. We have used a morphological (immunocytochemical) approach to answer these questions. The primary function of this study was to evaluate the effects of short-term exposure (4 days) to varying doses of orally administered (+)-fenfluramine on 5-HT-immunoreactive nerve terminals in the frontal cortex of the rat. The frontal cortex was selected because it contains a homogeneous population of nerve fibers and terminals unlike other cortical regions, the hippocampus, striatum and the hypothalamus where a mixed population of coarse and fine fibers has been described. Since the previously reported effect of fenfluramine on 5-HT nerve terminals was the appearance of coarse fibers, the region of cortex selected for this study showed no coarse fibers in the pair-fed control. This essential feature of control regions has not been used in previous studies on this subject. The present study demonstrates that (+) fenfluramine produces a dose-dependent reduction in 5-HT immunoreactivity of 5-HT nerve terminals in the neocortex of adult rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1868327 TI - Modifications of tubulin heterogeneity during embryonic and postnatal stages in a specific region of mouse brain. AB - An auditory nucleus (the inferior colliculus of the mouse) was used to study the modifications of the heterogeneity of tubulin which occur at various stages of development and maturation. Both the cold-stable (CS) and cold-labile (CL) fractions of tubulin were analyzed by high-resolution isoelectric focusing. Our results suggest that tubulin heterogeneity is modified at critical stages of development and maturation, with specific variations of the two fractions. Stage E10 corresponding to the appearance of the first young neurons and axonal profiles is marked by the modification of the CS fraction with the emergence of isotypes alpha 5 to alpha 8 and beta 12 and beta 17. Stage E12 is characterized by the modifications of the CL fraction, particularly the beta-group; at this stage the first dendrites become visible. At birth, all isotypes increase in both the CL and CS fractions. At stages P7-P10 transient modifications of a group of both CS and CL fractions and of the beta group of CS fraction occur. These are associated with the emergence of isotypes beta 17 to beta 20 in the CL fraction. This period precludes the initial period of functional maturation of the auditory system which occurs from P10 to P20. During this period, the CL fraction (alpha and beta group) remains unmodified, whereas all isotypes of the CS fraction, except 3-4, display complex variations with an initial decrease until P12, an increase until P17, and a final decrease until P20.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868328 TI - Effects of lingual nerve and chewing cortex stimulation upon activity of the swallowing neurons located in the region of the hypoglossal motor nucleus. AB - This study focuses on motoneurons and interneurons in the region of the hypoglossal nucleus (XIIth) related to swallowing and chewing. In sheep anesthetized with halothane, we have used extracellular microelectrodes to study the effects of stimulation of the superior laryngeal nerve (SLN), the lingual nerve (LN) and the chewing cortex (CCx) upon activities of the swallowing neurons (SNs). Ipsilateral stimulation (1-5 pulses at 500 Hz) of the peripheral afferents or CCx did not generally induce a short latency activation of the hypoglossal swallowing motoneurons (Group I SNs) since only 4 motoneurons (69 tested) were activated by the SLN, 4 motoneurons (56 tested) by the LN and none by the CCx. In contrast, the same stimulations were more effective with swallowing interneurons (Group II SNs) located in the reticular formation close to the XIIth motor nucleus since 12 neurons (30 tested) were activated with short latencies (9 +/- 1.8 ms; mean latency +/- S.D.) by the SLN, 9 neurons (21 tested) by the LN (latency; 8 +/- 1.8 ms) and 5 neurons (18 tested) by the CCx (latency: 13 +/- 1.7 ms). Seven neurons were activated by two or three modes of stimulation indicating the existence of convergent inputs upon some Group II SNs. During chewing movements induced by a prolonged stimulation (20-40 Hz) of the CCx, 10 Group I SNs (16 tested) versus only one Group II SN (8 tested) were found to fire in association with the jaw opening. Moreover, 3 motoneurons and 4 interneurons inactive during swallowing discharged during chewing movements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868329 TI - Spatial and temporal variation of microstimulation thresholds for inhibiting the tail-flick reflex from the rat's rostral medial medulla. AB - Suppression of the tail-flick reflex by microstimulation of the rostral medial medulla in rats lightly anesthetized with barbiturates was studied with regard to spatial and temporal variations in electrical threshold. Trains of constant current pulses with linearly descending amplitudes (called 'ramps') were passed through the extracellular brain microelectrode during noxious heating of the tail. The pulse amplitude at the time of the reflex, after allowance for conduction and reaction latencies, was taken as the threshold reading. This new method revealed a range of vertical electrode positions corresponding roughly to the nucleus raphe magnus, where the thresholds tended to be lowest (a mean of 4.1 microA for 0.4-ms pulses delivered at 50 Hz). In confirmation of the technique's validity neither the duration of the ramp nor its starting amplitude, within their useful range, significantly affected the measured threshold. Pronounced temporal fluctuation was seen in thresholds measured every 2 min. Spatial variability within the low-threshold region and differences between preparations were statistically much smaller sources of variation. The temporal fluctuation appeared to have a stationary mean for at least 20 min under constant conditions of anesthesia. In some experiments, action potentials from single neurons were recorded through the stimulating electrode, and classified into those inhibited during the tail-flick (off-cells), those excited (on-cells), and those unaffected (neutral cells). The thresholds where off-cells exhibited their maximum action potential were on average significantly lower than corresponding thresholds for on-cells. Short-range (less than 0.2 mm) spatial variations in the threshold appeared however to be uncorrelated with the distance to an individual recorded off-cell or on-cell.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868330 TI - Evidence for motility and pinocytosis in ramified microglia in tissue culture. AB - Ramified microglial cells were investigated in primary cultures of dissociated cerebral cortical tissue from rats. The identification of these cells was confirmed through immunohistochemical staining with 7 monoclonal antibodies selective for microglia. While there was significant variation in staining intensity with different antibodies, all stained the identified ramified cells; the antibodies OX-42 and ED1 yielded the most intense immunoreactivity. Based on distinctive morphological features, the microglia could be identified in living cultures where they were monitored using time-lapse video recording. This technique revealed extremely dynamic features of cellular plasticity and motility. Ramified microglia exhibited constant and rapid alterations in the size and shape of their cell body with an associated extension and retraction of processes; concomitantly, the cells moved about in a circumscribed area. These features of plasticity and motility were unique to this cell type, and correlated with OX-42 immunostaining. The microglia also possessed a differentially high level of pinocytotic activity; this too was correlated with OX-42 staining. From the nature of their morphological plasticity and motility, high pinocytosis, and cellular distribution, it is hypothesized that the ramified microglia specifically function as a system of fluid cleansing in normal brain tissue. PMID- 1868331 TI - Modulation of human short latency reflexes between standing and walking. AB - Inhibition of the magnitude of soleus muscle homonymous (H) reflexes occurs in humans when walking, compared to standing. The current study asked, (1) was the task modulation of Ia reflexes limited to soleus muscle, (2) was there support for attributing a presynaptic source to the inhibition in humans and (3) did an oligosynaptic short latency reflex show similar task modulation? In 3 subjects, H reflexes were evoked in vastus medialis and soleus, at 4 levels of contraction in the target muscle, with constant stimulus intensity when walking and standing. The reflex magnitudes in both muscles were significantly inhibited during the contractions for walking, compared to standing. Such inhibition also occurred in H reflexes of tibialis anterior muscle. An excitatory oligosynaptic reflex was then evoked in vastus medialis, through low intensity stimulation of the common peroneal nerve during walking and standing. The mean amplitudes of this reflex were not significantly different (P less than 0.05) between the two conditions, at any contraction level. The depression of quadriceps H reflexes, compared to the oligosynaptic reflexes through the same quadriceps motoneuronal pool in the same task, strongly suggested that the inhibition of H reflexes arose at other sites besides the motoneuronal cell body and proximal dendrites. We conclude that Ia H reflexes of various leg muscles of humans are inhibited when walking but that this does not generalize to the oligosynaptic short latency reflex between the anterior shank and thigh. PMID- 1868332 TI - Distribution of muscarinic receptors in the developing rodent cerebellum. AB - The distribution of muscarinic receptors in the developing rodent cerebellum was studied by light microscopic autoradiography of [3H]quinuclidinyl benzilate binding sites. Muscarinic receptors were not detected in the mouse cerebellar plate until embryonic day 16, at which time they were clustered in the ventromedial region of the cerebellar anlagen. At postnatal day 1, additional areas of higher grain density became visible in the dorsolateral medullary zone, internal to the newly forming granular layer. Labeling increased throughout the entire cerebellum between postnatal days 5 and 10, becoming markedly higher in the lateral hemispheres than in the vermis. This elevated density of binding sites in the hemispheres became reduced to that of the vermis by postnatal day 13 in the mouse, and PD20 in the rat. In adult animals, the cortical grain density was highest in the granule and Purkinje cell layers, low in the molecular layer and absent from the white matter. Receptor labeling was, however, observed over many areas of white matter throughout early development; this became more restricted to specific tracts during the third postnatal week. At no time during development were binding sites observed in the external germinal layer. Microvessels and capillaries, structures which have been shown to contain [3H]quinuclidinyl benzilate binding sites, may partially account for the observed ontogenic pattern. PMID- 1868333 TI - Learning-specific differences in Purkinje-cell dendrites of lobule HVI (Lobulus simplex): intracellular recording in a rabbit cerebellar slice. AB - The cerebellum has been directly implicated in the associative learning exemplified by classical conditioning of the rabbit nictitating membrane response. Lesions of cerebellar lobule HVI (Lobulus simplex) can disrupt or even abolish classical conditioning. Electrical stimulation of inputs that converge at cerebellar lobule HVI and the deep cerebellar nuclei has been shown to support classical conditioning of the responses elicited by such stimulation. Here we report that intracellular recording in a slice of rabbit cerebellar lobule HVI revealed a conditioning-specific increase in the excitability of Purkinje-cell dendrites without significant changes in dendritic membrane potential or input resistance. The finding of a conditioning-specific change in lobule HVI lends support to the theory that associative learning involves local dendritic modification and provides further evidence for the involvement of the cerebellar cortex in classical conditioning of the rabbit's nictitating membrane response. PMID- 1868334 TI - Transplantation of ventral forebrain cholinergic neurons to the hippocampus ameliorates impairment of radial-arm maze learning in rats with AF64A treatment. AB - Two types of cholinergic neurons were transplanted into the hippoccampus of adult rats chemically damaged by lateral ventricular administration of AF64A, a cholinergic neurotoxin, and the effects were compared with respect to their ability to reinnervate the hippocampus and to repair behavioral deficit. Pieces of brain tissue containing the nucleus basalis magnocellularis (NBM) or the striatum were taken for grafting from 17-day rat fetuses. About 3 months after transplantation, the rats with bilateral NBM grafts showed significant amelioration in radial-arm maze performance and habituation to a novel environment in an open field box, although they had not recovered to the control level. In rats with NBM grafts that showed a good performance, there were surviving grafts and many ingrowths of AChE-positive fibers in the hippocampus. By contrast, rats with striatal grafts showed hardly any significant improvement in these behavioral measures. The AChE staining revealed poor outgrowth of the striatal grafts into the hippocampus. These results indicate that grafting of NBM cholinergic neurons, which are anatomically similar to septal neurons, into the hippocampus produces a partial restorative effect on the cognitive impairment associated with hypofunction of the septohippocampal system. PMID- 1868335 TI - Immunohistochemical and immunoelectron microscopical characterization of cerebrovascular and senile plaque amyloid in aged dogs' brains. AB - Immunohistochemical and immunoelectron microscopical studies were carried out on 28 aged dogs' brains. Amyloid deposits were seen in the arteries and capillaries in the leptomeninges and in superficial areas of the cortices in 19 (67.9%) of the 28 dogs (10-22 years of age). Immunohistochemically, these amyloid deposits were reactive for anti-beta/A4 antibody. Additionally, a variable number of parenchymal deposits with diffuse beta/A4-immunoreactivity (diffuse plaques) was also noted throughout the cerebral cortex in 24/28 dogs (85.7%). However, these plaque lesions were undetectable in Congo red staining. Electron microscopically, amyloid fibrils, measuring 10 nm in width, were located mainly in the tunica media of the arteries, and in less involved vessels they tended to be present among collagen fibres in the adventitia and smooth muscle cells in the outer layer of the media. The plaque lesions appeared to contain sparse aggregations of amyloid fibrils. In immunoelectron microscopical examinations, all amyloid fibrils in both blood vessels and plaques were selectively labelled by gold particles. These findings indicate that aged dogs can provide a useful experimental model for research into the beta/A4-type of cerebral amyloidosis commonly seen in Alzheimer's disease. PMID- 1868336 TI - Effects of circadian phase and duration of sleep deprivation on sleep and EEG power spectra in the cat. AB - The electroencephalogram (EEG) of cats was recorded under baseline conditions (LD 12:12) and after 4 and 8 h of sleep deprivation (SD). The EEG was analyzed by visual scoring and by spectral analysis. Under baseline conditions the 24-h distribution of sleep was bimodal: the smallest amounts of sleep occurred at the light-dark and dark-light transitions. EEG slow-wave activity (power density in the delta frequency range: 0.5-4.0 Hz) in non-rapid-eye-movement sleep (NREMS) showed a small variation over the 24-h period. When recovery sleep, following 4 h and 8 h of SD, started at the beginning of the dark period, no significant rebound of NREMS and REMS occurred during the 24-h recovery period. When recovery sleep, after 4 h of SD, started at the fifth hour of the light period, the amount of NREMS was increased. In all experiments the EEG power density in NREMS was enhanced after SD in the entire frequency range studied (0.5-31.5 Hz), but more prominently in the delta and theta (4.5-7.0 Hz) frequency bands. The effects dissipated in the course of the recovery period. The magnitude and duration of the enhancements of EEG power densities were dependent on the duration of SD and on the circadian phase at which SD was scheduled. It is concluded that in the cat sleep is a function of both circadian and homeostatic processes and that especially the EEG power density in NREMS is highly responsive to sleep loss. PMID- 1868337 TI - Diazepam enhances intrasynaptosomal free calcium concentrations. AB - Synaptosomes prepared from brains of rats were incubated in different concentrations of diazepam under conditions designed to reduce the action of a reversed Na+/Ca2+ exchanger. In synaptosomes depolarized in the presence of added Ca2+, doses of diazepam ranging from 0.1 to 100 microM were found to significantly enhance Ca2+ levels measured with the fluorescent dye fura-2, compared to control incubations without drug. Furthermore, doses of diazepam as low as 1 microM significantly increased the concentration of Ca2+ in non depolarized synaptosomes without added Ca2+ in the medium. The effects of depolarization and diazepam treatment were synergistic in increasing the levels of intrasynaptosomal Ca2+. PMID- 1868338 TI - Cutaneous afferent activity in the median nerve during grasping in the primate. AB - Neural activity was recorded from the median nerve of a monkey during grasping and lifting, using a chronically implanted cuff electrode. At the onset of lifting, there was an initial dynamic response during which the intensity of the neural signal increased rapidly. This neural response attained its peak value well before the displacement, the load force or the grip force. The time course and peak of the rectified, integrated neurogram were best correlated with the rate of change of grip force. The neural activity declined exponentially to a steady value following the initial peak. During steady holding the mean amplitude of the neurogram was best correlated with the mean grip force. At the end of the holding phase there was a short burst of neural activity as the monkey relaxed the grip force and released the object. During some blocks of trials pulse perturbations were applied to the object. When the monkey did not increase the grip force in advance of the perturbation, the perturbation produced a relatively large displacement of the object and a burst of neural activity whose onset coincided with the onset of displacement. When the monkey anticipated the perturbation by increasing the grip force during the holding period preceding the perturbation, the perturbation produced a relatively small displacement and relatively little increase in neural activity. PMID- 1868339 TI - Species differences in cerebral taurine concentrations correlate with brain water content. AB - The notion that taurine (Tau) has an osmoregulatory function in the mammalian brain has not been established, although it has been reported that the severity of hyponatremic edema is proportional to cerebral [Tau]. Tau pools are not easily altered in vivo, but the fact that there are large differences in cerebral taurine levels between mice, rats and guinea pigs offers an opportunity to determine whether endogenous Tau affects volume regulation of the brain in hyposmolal conditions. This issue was investigated by injecting saline or distilled water intraperitoneally at 150 ml/kg in anesthetized mice, rats and guinea pigs. The animals were decapitated 4 h later, and blood osmolality, cortical specific gravity, Na+, K+ and amino acid concentrations were determined. In controls, blood osmolality and specific gravity of the cortex were highest in the mouse (304 +/- 3 mmol/kg; 1.0488 +/- 0.0003 kg/l), followed by the rat (294 +/- 1; 1.0462 +/- 0.0002) and the guinea pig (285 +/- 2; 1.0445 +/- 0.0002). There was a correlation between these measures and cortical Tau levels which were 10.31 +/- 0.36 mmol/kg in mouse cortex, 6.31 +/- 0.18 in rat cortex and 1.37 +/- 0.06 in guinea pig cortex. Despite these differences, water-induced cerebrocortical swelling did not differ between the species studied. Interspecies variation in cortical osmolality did not relate to [Na+] and [K+], since the levels of these electrolytes were higher in the guinea pig cortex than in the rat and mouse cortex. After administration of water, the levels of Na+ and K+ were reduced in rat and guinea pig cortex, while only [Na+] was significantly decreased in mouse cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868340 TI - Hippocampal type I and type II corticosteroid receptor affinities are reduced in rats predisposed to develop amphetamine self-administration. AB - It has been suggested that individual predisposition to develop amphetamine self administration is associated with impairment in corticosteroid negative feedback mechanisms. Since corticosteroid receptors, particularly those in the hippocampus, are involved in corticosterone feedback sensitivity, we examined the relation between individual differences in amphetamine self-administration and characteristics of hippocampal corticosteroid receptors. Rats were selected on the basis of likelihood to self-administer amphetamine and designed as: (1) High Responding (HR) rats, who quickly acquire the response and (2) Low Responding (LR), who fail to self-administer amphetamine. We found lower affinities both for hippocampal type I and type II corticosteroid receptors in the HR animals. These data suggest that modification of hippocampal corticosteroid receptors may be responsible for the predisposition of some animals for amphetamine self administration. Because HR rats also show a greater behavioral and endocrinological response in a novel environment, these differences in affinities suggest a relation among amphetamine self-administration, control of the corticosterone feedback loop, serum levels of corticosterone and characteristics of hippocampal corticosteroid receptors. The implication is that pharmacological manipulations of corticosteroid receptors may reveal new therapeutic strategies for drug abuse. PMID- 1868341 TI - Acute cocaine administration: effects on local cerebral blood flow and metabolic demand in the rat. AB - Local cerebral blood flow and glucose utilisation were measured in both saline (n = 10) and cocaine (10 mg/kg; n = 10) treated rats using [14C]iodoantipyrine and [14C]2-deoxyglucose quantitative autoradiography respectively. In control animals, the ratio of flow to metabolism was 1.40 (r = 0.92) for the 40 brain regions examined. Cocaine treatment altered neither the correlation (r = 0.83) nor the ratio (1.49). Thus, the fundamental relationship between CBF and metabolism remains intact following acute cocaine exposure. PMID- 1868342 TI - 'Anxiolytic' effect of CCK-antagonists on plus-maze behavior in mice. AB - The effects of systemic treatment with the CCK-B receptor antagonist L-365,260, its 3S-(-) enantiomer and the CCK-A receptor antagonist devazepide were assessed in the plus-maze procedure in mice. L-365,260 (1-1000 micrograms.kg-1 i.p.) produced a dose-dependent increase in the percentage of entries into, and the percentage of time spent in the open arms. Total arm entry was not consistently modified. Neither the 3S-(-) enantiomer of L-365,260 nor devazepide (both administered at 100-10,000 micrograms.kg-1) enhanced the exploratory behavior of mice. These results suggest that CCK-B, rather than CCK-A antagonists may possess 'anxiolytic' properties in mice. PMID- 1868343 TI - Effects of intracerebroventricularly administered neostigmine on sympathetic neural activities of peripheral tissues in rats. AB - Sympathetic nervous activity (SNA) in the liver, heart, pancreas and interscapular brown adipose tissue was examined 60 min after the third cerebroventricular injection of neostigmine (5 x 10(-8) mol) in rats. We employed the technique of specific gas chromatography-mass spectrometry for simultaneous analysis of norepinephrine (NE) and its primary neuronal metabolite, 3,4 dihydroxyphenylethyleneglycol (DHPG) and used the ratio DHPG/NE as an index of SNA. Neostigmine produced significant increases in the DHPG/NE ratio in all tissues investigated. Co-administration of atropine with neostigmine completely inhibited this neostigmine-induced effect. These findings suggest that the central cholinergic-muscarinic activation with neostigmine stimulates SNA in the peripheral tissues examined. PMID- 1868344 TI - Calcium, magnesium, and long-term recovery from hypoxia in hippocampal tissue slices. AB - Ortho- and antidromic responses recovered and remained robust for 5 h in slices exposed to transient hypoxia in low calcium, while responses remained depressed in slices made hypoxic in normal calcium. Elevating magnesium in addition to reducing calcium did not improve recovery compared to reducing calcium alone. Spreading depression-like hypoxic depolarization occurred earlier in low calcium than in control fluid. We conclude that loss of function was triggered by calcium uptake by neurons and not by cell swelling, and that activation of NMDA receptors probably played no part. PMID- 1868345 TI - GDP beta S antagonizes whole-cell current responses to excitatory amino acids. AB - Guanine nucleotides have been predicted to be NMDA antagonists in tissue binding studies. Using the patch-clamp technique, we now show that the guanine nucleotide GDP beta S produces a rapidly reversible antagonism of NMDA, kainate, and, less potently, quisqualate whole-cell current responses. Furthermore, it does not appear that this antagonism is effected intracellularly. Our results suggest a novel extracellular role for guanine nucleotides apart from their traditional intracellular actions on G-proteins. PMID- 1868346 TI - Phospholipase C isozymes in neurons and glial cells in culture: an immunocytochemical and immunochemical study. AB - Expression of 3 brain isozymes of phospholipase (PLC-beta, PLC-gamma and PLC delta) was investigated in relation to cell types found in rat CNS cultures. Immunoreactivity of cultured neurons, astrocytes and oligodendrocytes was demonstrated for all of the 3 isozymes by immunocytochemical staining and immunoblotting, with some differences in reaction intensity. Immunoblotting revealed that the level of expression was neurons greater than oligodendrocytes greater than astrocytes for PLC-beta and PLC-gamma, and astrocytes greater than oligodendrocytes greater than neurons for PLC-delta. PMID- 1868347 TI - The effect of estrogen on the estrogen receptor-immunoreactive cells in the rat medial preoptic nucleus. AB - The localization of estrogen receptor-immunoreactive (ER-IR) cells in the medial preoptic nucleus (MPN) and the effect of estrogen upon these cells were quantitatively analyzed by immunohistochemistry using a monoclonal antibody to estrogen receptor (ER) protein in rat. ER was distributed in the nucleus of MPN neurons and was not detected in either cytoplasm or glial cells. There were more ER-IR cells with higher immunoreactivities in ovariectomized (OVX) rats than in estradiol (E2)-treated rats. The number of ER-IR cells in E2-treated compared with OVX rats was reduced by 43%. In particular, the number of ER-IR cells in the central part of the MPN was largely decreased. Our data indicate that the central part of the MPN is most sensitive to estrogen. PMID- 1868348 TI - Intrahippocampal transplants of septal cholinergic neurons: high-affinity choline uptake and spatial memory function. AB - Recent studies have demonstrated that intrahippocampal cholinergic septal grafts can ameliorate deficits in spatial memory function and hippocampal cholinergic neurochemical activity in animals with disruptions of the septohippocampal system. However, no study has determined if the restoration of spatial memory function is correlated to the restoration of cholinergic activity, as measured by high-affinity choline uptake (HACU). The present study was designed to determine if such a correlation between behavioral and neurochemical restoration exists. Male Sprague-Dawley rats received either sham lesions (SHAM), bilateral lesions of the septohippocampal pathway (LES), or bilateral lesions along with intrahippocampal septal grafts (SG). After 8 months, rats were tested for their ability to perform spatial reference, spatial navigation and working memory tasks. Upon completion of the behavioral testing, neurochemical activity of the hippocampus was measured by HACU. The results indicate that animals in the SG group had significantly higher behavioral scores and hippocampal HACU rates than animals in the LES group. Regression analysis indicates that a significant correlation exists between performance on each behavioral task and HACU rates. These results demonstrate that hippocampal cholinergic activity, as measured by HACU, correlates significantly with performance on tests of spatial memory function. PMID- 1868350 TI - Sensitivity of lateral hypothalamic neurons to glycemic level: possible involvement of an indirect adrenergic mechanism. AB - Most of the lateral hypothalamic neurons responding to moderate changes in blood glucose fail to be affected by direct glucose applications. Therefore their sensitivity to glycemic level must be mediated by an indirect mechanism. In order to test whether adrenergic afferents might be involved, the activity of lateral hypothalamic neurons was recorded during hyperglycemia and local glucose and epinephrine microiontophoresis. A majority of the recorded cells sensitive to local epinephrine responded to this substance with a decrease in activity. While no consistent correspondence was found between the responses of the same cells to local glucose and epinephrine ejections, almost all the neurons sensitive to glycemic alterations responded in the same direction to hyperglycemia and iontophorised epinephrine. These results support the view that the activity of lateral hypothalamic cells can be modulated in relation to changes in glycemic level through adrenergic signals released by some neurons which are sensitive to the blood glucose. The possible localization in the solitary tract area of such neurons projecting to the lateral hypothalamus is discussed. PMID- 1868349 TI - Quiescent astroglia in long-term primary cultures re-enter the cell cycle and require a non-sterol isoprenoid in late G1. AB - Astroglia proliferate during brain growth, and can divide again later, particularly during astrogliosis. We investigated whether astroglia in primary cultures of newborn rat brain similarly achieve a state of prolonged quiescence which enables re-entry into the cell division cycle. In cultures after 2 months, cell number plateaued and there were sharp decreases in [3H]thymidine incorporation (70 +/- 5 vs 4 +/- 0.5 cpm/micrograms protein/h at 30 and 60 days, respectively) and in percentages of cell nuclei incorporating bromodeoxyuridine (BrDU) (from 46 +/- 6% to less than 1%). Replating at 10(4) cells/cm2 yielded secondary cultures which synthesized DNA actively. Forty-eight hours of serum deprivation at 2-3 days from subculturing, followed by addition of 10% serum (time 0), resulted in a return to quiescence which persisted until 12 h (G0 + G1). By 20 h (S phase), there were abrupt increases in DNA synthesis (5-fold) and in BrDU-labeled nuclei (from 19 +/- 2 to 76 +/- 8%) and the percentage of glial fibrillary acidic protein (GFAP)-positive cells declined to 14 +/- 2%. Three days later, GFAP-positive cells numbered around 80%. Cell cycling after prolonged quiescence, in a manner similar to that in early astroglial cultures, required a non-sterol derivative of mevalonate in late G1. These data confirm that astroglia in primary cultures, like their counterparts in vivo, have a flexible capacity to enter and depart from quiescence, and most importantly, provide a system for examining regulation of this process. PMID- 1868351 TI - Stereotaxic atlas of the brainstem of the muskrat, Ondatra zibethicus. AB - The muskrat is an aquatic rodent of moderate size and possesses dramatic respiratory and cardiovascular behaviors in response to submersion, stimulation of the upper respiratory tract, or environmental cues. This report provides a stereotaxic atlas of the muskrat's brainstem in the transverse plane to facilitate studies requiring an accurate localization of discrete brain structures. Plates are presented of brainstem sections between the obex and superior colliculus separated by 450 microns. Each figure shows a Nissl stained hemisection complemented by a line drawing. Our data shows mature muskrats have relatively uniform craniometric dimensions promoting their use for stereotaxic placements in their brains. PMID- 1868352 TI - Noradrenaline-like terminals in the cat nucleus ventralis posterior of the thalamus. AB - Noradrenaline-like immunoreactivity in the cat nucleus ventralis posterior of the thalamus was investigated using an indirect immunocytochemical technique. Specific antinoradrenaline antibodies, raised in rabbits, were used. It was first verified that these antibodies recognize noradrenaline cells bodies of the locus coeruleus and their ascending axons in the ascending noradrenergic tract. In the nucleus ventralis posterior itself, noradrenaline-like fibers were observed. They were either randomly distributed or grouped around nonlabeled cell bodies. These neurons were generally oblong and measured 60-80 microns. With electron microscopy, preliminary results showed immunoreactive fibers in close apposition to unlabeled cell bodies or dendrites. The precise nature of these profiles was sometimes difficult to ascertain, since experiments were done in presence of detergent. In some cases symmetric synapses might be observed between immunoreactive axon terminals and unlabeled dendrites. The specificity of the reaction is discussed in the light of several control experiments. PMID- 1868353 TI - Reduction of exploratory behavior by intraperitoneal injection of interleukin-1 involves brain corticotropin-releasing factor. AB - The behavior of mice was scored in a multicompartment chamber one hour following intraperitoneal injection of recombinant human interleukin-1 (IL-1). Both IL-1 alpha and IL-1 beta dose-dependently reduced the mean duration for which mice were in contact with novel stimuli without altering measures of locomotor activity, such as movements between the compartments or rears. These behavioral changes resemble those previously observed with prior restraint or intracerebroventricular (ICV) injection of corticotropin-releasing factor (CRF). Effective doses were in the range 0.1-10 ng for IL-1 alpha, and 1-10 ng for IL-1 beta. The reduction in stimulus-contact times induced by 1 ng of IL-1 beta was reversed by prior ICV injection of the CRF antagonist, alpha-helical CRF9-41, suggesting that IL-1 causes secretion of brain CRF which in turn elicits the behavioral changes. These results indicate that peripheral administration of IL-1 alpha or IL-1 beta in low doses can alter behavior. They provide additional evidence that IL-1 administration stimulates brain CRF secretion, and that brain CRF can modulate exploratory behavior, and thus reinforces the concept that IL-1 administration can induce stress. PMID- 1868355 TI - Time dependent loss of tissue GABA content and immunoreactivity in hippocampal slices. AB - Immunohistochemical detection of GABA was used to evaluate changes of the GABA innervation in hippocampal slices maintained in vitro. In parallel experiments the amount of GABA, glutamate and aspartate was measured with high performance liquid chromatography. The results showed that while glutamate and aspartate levels remained fairly constant, GABAergic neurons suffered remarkable alterations. During 8 hours' incubation the GABA content of the tissue and the number of GABA containing neuronal cell bodies decreased by 79.7% and 84.6%, respectively. The qualitative features of the immunoreactivity of the neuropil did not change. In conclusion, while in hippocampal slices tissue glutamate and aspartate levels are only slightly affected by the in vitro maintenance, more than half of the tissue GABA content is lost during prolonged in vitro incubation. As a consequence of the GABA loss, the ratio of endogenous inhibitory and excitatory amino acid transmitters has been altered, which could influence the viability of adult hippocampal tissue in vitro conditions. PMID- 1868356 TI - Cholinergic actions of diazepam and atropine sulfate in soman poisoning. AB - The effectiveness of diazepam alone or in the presence of atropine sulfate in reversing soman-induced convulsions, inhibition of blood and brain cholinesterase (ChE) activity, and elevation of brain acetylcholine (ACh) and choline (Ch) concentrations in rats was studied. Diazepam (5 mg/kg, IM) blocked the convulsive activity of soman (100 micrograms/kg, SC) whereas atropine sulfate (12 mg/kg, IM) did not. Inclusion of atropine sulfate enhanced the anticonvulsant effects of diazepam. Neither diazepam nor atropine sulfate alone affected ChE activity in the blood and brain of rats, nor did they alone, or in combination, reverse the ChE inhibition induced by soman. Diazepam by itself caused an increase in ACh concentrations in the striatum and a decrease in Ch concentrations in the cortex and striatum. On the other hand, atropine sulfate produced a decrease in ACh and an increase in Ch concentrations in these two brain regions. With combined treatment, diazepam reversed the effect of atropine sulfate on brain ACh and Ch concentrations. Diazepam attenuated the soman-induced elevation of ACh and Ch concentrations in most of the brain regions studied, while atropine sulfate did not. Only when diazepam was given concurrently with atropine sulfate did the elevated brain ACh or Ch concentrations induced by soman return to normal. These results suggest that the anticonvulsant activity of diazepam in soman poisoning may be partially related to its action on presynaptic cholinergic mechanism. PMID- 1868354 TI - Cholecystokinin-like immunoreactivity in the rat spinal cord: effects of thoracic transection. AB - A study of cholecystokinin-like immunoreactivity in the lumbar (L1-L5) spinal cord segments of rats was realised 24-48 hours after complete thoracic transection (T6-T8). A comparison was made with corresponding spinal cord segments from control and sham-operated animals. The immunocytochemical study with light microscopy showed cholecystokinin-like immunoreactive cell bodies in laminae VII and X at L1-L5, caudal to the transection. In addition, the immunoreactivity was greatly enhanced in bundles of the dorsolateral funiculus compared to sham-operated animals. Our results suggest that part of cholecystokinin-like cell bodies of laminae VII and X send projections to supraspinal sites. Some of these supraspinal projections would go through the dorsolateral funiculus. In the lumbar dorsal horn of operated animals, the immunoreactivity was greatly enhanced in lamina I, while it was slightly decreased in lamina II, compared to control animals. Using electron microscopy, in lamina I, the immunoreactivity localized in different neurites was generally very intense. Moreover, axon terminals showed swelling: their mean size was 0.8 1.8 microns (0.5-1.2 in control animals). This result suggests that some cholecystokinin-like neurons also project to lamina I of rostral cervical segments. In lamina II, numerous degenerating axons were observed (24 hours after thoracic spinal transection). This would suggest that part of descending cholecystokinin-like projections terminate in lamina II. PMID- 1868357 TI - Neuronal activity in visual, auditory and polysensory areas in the monkey temporal cortex during visual fixation task. AB - The activity of 252 neurons in the inferotemporal visual area TEO, the superior temporal auditory area (AA), and the superior temporal polysensory area (STP) during the performance of a visual spot-fixation task and two variations, blink and tone tests, was examined in two behaving monkeys. A considerable number of not only TEO cells (45%) but also AA (29%) and STP (34%) cells were activated during the spot-fixation task, but unresponsive to the blanking of the spot during the fixation stage in the blink test. In addition, it was found that the activity of a third of the TEO, AA and STP cells which fired during the task start stage in the spot-fixation task was modulated by cross-interaction between spot and tone simultaneously presented in the tone test: among these, the spot induced activity of all TEO cells was enhanced by the tone, whereas the spot induced activity of all AA and STP cells was suppressed by the tone. These findings are discussed in relation to the process of attending selectively to a fixation-spot. PMID- 1868358 TI - The innervation of the levator veli palatini muscle by the glossopharyngeal nerve. AB - We developed a novel method which enables bloodless exposure of the levator veli palatini muscle in rat in order to investigate the physiological properties of this muscle. The levator veli palatini muscle which is innervated by a branch of the glossopharyngeal nerve showed rhythmic spontaneous movement in rats. Cutting the branch supplying LVP of the glossopharyngeal nerve caused cessation of the spontaneous movement of the levator veli palatini muscle. The spontaneous discharges of the glossopharyngeal nerve were synchronized with those of the phrenic nerve. A mixture of 95% oxygen and 5% room air influenced the efferent discharges from the branch of the glossopharyngeal nerve supplying the levator veli palatini muscle. These findings indicate that the motor nerve supply to the levator veli palatini muscle is the glossopharyngeal nerve, and the levator veli palatini muscle is related to the respiratory system, in particular with inspiration in rats. PMID- 1868359 TI - Quisqualate lesions of rat NBM: selective effects on working memory in a double Y maze. AB - Some authors have reported that quisqualic acid lesions of the nucleus basalis magnocellularis (NBM), although producing large cortical cholinergic losses, have little effect on memory. The purpose of the present study was to investigate the effects of quisqualic acid lesions of the NBM on working and reference memory in a double Y-maze. Each trial started with placement into one of the two end arms of the first Y-maze, and the correct response was to go down the stem (reference memory). Access was then given to the second Y-maze, the correct response being conditional upon the side of the first Y-maze from which that trial had begun (working memory). Rats were trained to an 88% correct criterion and were then given either bilateral quisqualic acid (60 nM, 0.5 microliters) or sham lesions (0.9% saline, 0.5 microliters) of the NBM. One week postsurgery, rats were tested on the double Y-maze task with delays of 0, 5 or 30 seconds being introduced prior to both the working and reference memory choice. NBM lesions produced a 63.2 +/- 6.2% decrease of cortical choline acetyltransferase (ChAT) compared to unoperated controls. Delays affected only the working memory of the sham group. Rats with lesions showed a significant impairment of working memory at all delays, but no change in reference memory. Results indicate that quisqualic acid lesions of the NBM that produce significant reductions in cortical ChAT selectively impair working memory. PMID- 1868360 TI - Effects of the novel compound Hoe 065, a central enhancer of cholinergic activity, on voluntary alcohol consumption in rats. AB - Hoe 065 is a compound structurally related to the angiotensin converting enzyme inhibitors and capable of increasing central cholinergic activity. The effects of this compound were studied on alcohol intake and on the reduction in alcohol intake produced by abutapril, an angiotensin converting enzyme inhibitor. Hoe 065 failed to alter alcohol intake or to modify the reduction in alcohol intake produced by abutapril. These findings suggest that enhanced cholinergic activity may not play a role in the control of alcohol consumption and may not be part of the mechanism by which the angiotensin converting enzyme inhibitors reduce alcohol intake. PMID- 1868361 TI - Decreased hyperthermic effect of MK-801 in selectively bred hypercholinergic rats. AB - The Flinders Sensitive Line (FSL) of rats has been selectively bred to have increased sensitivity to cholinergic agonists. However, these rats exhibit altered responsiveness to a number of noncholinergic agents, such as apomorphine, buspirone and ethanol. This study compared the FSL and control Flinders Resistant Line (FRL) rats in terms of their hyperthermic response to the phencyclidine (PCP) receptor agonist, MK-801 (0.2 mg/kg SC) and their MK-801 binding characteristics. We have found that FSL rats react with a delayed hyperthermia, having a significantly lower hyperthermia for the first 120 min of observation. Thereafter the response does not differ in FSL and FRL rats. Both groups had similar affinities and numbers of [3H]MK-801 binding sites in the hippocampus/cerebral cortex. Pretreatment with scopolamine (1 mg/kg SC) failed to affect MK-801-induced hyperthermia in either line of rats. These findings suggest that selective breeding of FSL rats attenuated the secondary mechanisms involved in the PCP receptor-mediated hyperthermic response. However, by itself cholinergic supersensitivity does not appear to be a major factor in the blunted responsiveness of FSL rats to MK-801. PMID- 1868362 TI - The effects of THA on scopolamine and nucleus basalis lesion-induced EEG slowing. AB - The effectiveness of THA (an anticholinesterae) on scopolamine (0.4 mg/kg) and nucleus basalis (NB) lesion-induced change in neocortical spectral electroencephalography (EEG) were investigated. Scopolamine increased the amplitudes of all the spectral components in waking-immobility. In the movement related EEG spectral values, only the alpha power was increased. THA 7.5 mg/kg, but not THA 3 mg/kg, could reverse scopolamine-induced amplitude change. NB lesioning increased delta and theta amplitudes, but decreased beta amplitude. Delta amplitude was increased during movement recordings in NB-lesioned rats. THA 7.5 mg/kg and pilocarpine 10 mg/kg, but not THA 3 mg/kg, could partially reverse the increase of delta and theta amplitudes induced by NB lesions. However, the beta power decrease could not be restored with cholinomimetics. This study demonstrates that quantitative EEG activity analysis may reflect the THA-induced restoration of the function of the cholinergic nucleus basalis. PMID- 1868363 TI - Effects of mercury and lead on rubidium uptake and efflux in cultured rat astrocytes. AB - Astrocytes readily sequester lead and mercury (8, 10, 19, 22). Accordingly, studies were undertaken to assess the effects of lead and mercury on homeostatic functions in neonatal rat brain primary astrocyte cultures. Both inorganic and organic mercury, but not lead, significantly inhibited the initial rate (5 min) of uptake of 86RbCl, used as a tracer for K+, at concentrations of 10-100 microM. Mercury and to a lesser extent lead also stimulated the efflux of intracellular 86Rb+ at 10-500 microM. These observations suggest that the astrocyte plasma membrane may be an important target for lead and mercury, and that relatively low concentrations of these heavy metals should inhibit the ability of astrocytes to maintain a transmembrane K+ gradient. PMID- 1868364 TI - Photochemically induced thrombosis of the precentral cortex impairs operant variable-interval spatial delayed alternation performance by rats. AB - A variable-interval spatial delayed alternation memory task was used to quantify the behavioral effects of photochemically induced thrombic infarction of the precentral (frontal) cortex. Upon achieving criterion on the behavioral task, rats received thrombicischemic lesions, predominantly limited to the medial precentral cortex, induced by injection of the fluorescein dye Rose Bengal and illumination of the skull above the target area. Beginning six days after surgery, rats were retested on the memory task. Compared to Sham-operated controls (n = 5), rats with precentral cortex lesions (n = 5) demonstrated a retention interval-dependent accuracy deficit (impaired at the longest retention interval only) and slower reaction time (increased response latency). These effects were significant only during the first week of postoperative testing. Rats with lesions also demonstrated a greater probability of a choice response throughout the three postoperative test weeks. The results suggest that photochemical thrombosis in the precentral cortex produces functional, behavioral consequences in rats which can be reliably and objectively measured. PMID- 1868365 TI - Regional effects of iminodipropionitrile (IDPN) on free radical scavengers in rat brain. AB - Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured in different regions of the brains of control and IDPN-treated rats. IDPN treatment resulted in significant increase of SOD activity in the cerebellum. Other regions, except frontal cortex, exhibited a slight decrease. While there was no significant difference in GSH-Px activity in all regions compared to controls, CAT activity was slightly increased in the cerebellum. These results give credence to the notion that free radical damage to certain areas of the brain such as isodendric core of the brainstem may play a role in the development of movement disorders. PMID- 1868366 TI - Aversiveness of motion and noise to broiler chickens. AB - 1. The aversiveness of motion and noise to broiler chickens was examined using a passive avoidance technique. Birds were initially trained to peck a key a fixed number of times to obtain food. After training, food could still be obtained by key pecking, but feeding was immediately followed by 1 min exposure to noise or motion. Birds could delay or avoid exposure by delaying or avoiding key pecking, hence foregoing food. Reduced pecking rate was therefore taken as a measure of aversion. 2. In experiment 1, simultaneous motion and noise, but not noise alone, resulted in a significant decrease in pecking rate in comparison with baseline rates obtained after training. 3. In experiment 2 there was no significant difference in the pecking rates of 4 groups of broilers during training. However, after exposure to 1 of 4 types of motion, strongly significant differences in pecking rates were found between the groups. The mean latency to peak 3 times was significantly greater for birds exposed to gentle vibration, with a single jolt after 55 s, than for birds exposed to simple harmonic motion in either the horizontal or vertical plane. Birds exposed to circular motion in the horizontal plane had a significantly greater mean pecking latency than birds exposed to simple harmonic motion in the vertical plane. 4. Baseline latencies to keypeck in experiments 1 and 2 were longer than expected. In experiment 3 a direct comparison of baseline pecking was made between broilers and laying hens. The hens had significantly shorter pecking latencies. PMID- 1868367 TI - Implantation of chicken embryonic tissue and cells into unfertilised eggs. AB - 1. Chick embryo cells and halved embryos were successfully implanted into unfertilised eggs. Yolks containing implants were placed in recipient eggshells, covered by transparent vacuum-formed plastic cones and incubated for 72 h. 2. Dispersed cells were obtained from eggs expelled from the uterus or from eggs that had been laid. Implantation of these cells often resulted in aggregation and epithelial growth, in several cases with axial development. 3. Growth of implanted halved embryos of different ages was often observed, including one 10 somite embryo. Non-axial epithelia, sometimes with a central hole, a central fluid-filled cellular vesicle or a vesicle only, were also observed. 4. In another culture system, whole and halved embryos obtained from laid eggs were cultured on a vitelline membrane stretched across semi-solid egg albumen. During the 72 h incubation, axial development was observed only in whole embryos, while halved embryos grew either into epithelia containing fluid-filled cellular vesicles or into vesicles only. 5. It was found that daily drainage of the accumulating fluid from the embryo compartment encouraged axial development in halved embryos, and almost abolished vesicle formation. Holes were formed in half the embryos cultured on a vitelline membrane. 6. It appeared that physical and biological conditions could inflict serious malformations on the implants. PMID- 1868368 TI - Comparative gait analysis of two strains of turkey, Meleagris gallopavo. AB - 1. Economic requirements have encouraged farmers to select broad-breasted strains of turkeys (Meleagris gallopavo). These birds are very heavy (more than 30 kg), have pectoral hypertrophy and are frequently lame. Traditional turkeys, closer to wild birds, weigh 9 kg on average. 2. Gaits, which are motor pattern expressions, seem to be linked to species morphology. However, no significant differences are evident between the gaits of traditional and broad-breasted strains. 3. Yet, posterior views of the walk of both strains show lateral oscillations, which are very slight in the traditional one but very marked in the broad-breasted one. 4. In the latter, modification of the centre of gravity path may increase the energetic cost of walking and be associated with problems of lameness. 5. Therefore, if the genetic pool permits an increase in weight of broad-breasted turkeys, then extrinsic factors, such as gravity constraints, may limit this evolution. PMID- 1868369 TI - Gastrointestinal emptying in the final days of incubation of the chick embryo. AB - 1. The gastrointestinal (GI) emptying of the chick embryo was studied in days 19 and 20 of incubation using radioactive (14C-PEG-4000) and coloured (Evans Blue dye) tracer markers. 2. Following administration by oral cannula, the percentages of tracer marker recovered in the yolk sac and the GI tract showed the existence of a GI motor pattern in both 19 d and 20 d chick embryos and suggested that the fluids drunk by the chick embryo during the final days of incubation could have reached the yolk sac from the GI tract via the vitelline diverticulum. PMID- 1868370 TI - Inheritance of plasma insulin-like growth factor-I and growth rate, food intake, food efficiency and abdominal fatness in chickens. AB - 1. The inheritance of, and genetic and phenotypic correlations between, plasma insulin-like growth factor-I (IGF-I) and 28-(28dW) and 56-d (56dW) body weight, 28- to 56-d body weight gain (BWG), food intake (FI), food conversion ratio (FCR) and abdominal fatness (AF) at 56 d were determined by sib analyses in a population of 327 pedigreed progeny produced by matings between 18 cockerels and 72 pullets from a broiler strain of chickens bred at random for 8 generations. 2. Plasma IGF-I was measured in fed (IGF-If) and fasted (IGF-I) birds at 42 d. 3. Heritability estimates (sire + dam) were: 28dW 0.35 +/- 0.11, 56dW 0.49 +/- 0.13, BWG 0.51 +/- 0.13, FI 0.55 +/- 0.13, FCR 0.73 +/- 0.14, AF 0.49 +/- 0.13, IGF-If 0.10 +/- 0.08, IGF-Is 0.08 +/- 0.08. 4. The low heritability estimates with their high standard errors for the IGF-I measures precluded the calculation of meaningful genetic correlations between these and the performance traits. There were moderate to strong positive genetic correlations between 28dW, 56dW, FI and AF. PMID- 1868371 TI - Body Weight increase of indigenous pearl guinea fowl in Nigeria through cross breeding. AB - 1. The performance of the crossbreds of local unimproved Pearl (RBC) and improved local Pearl (SLP) with improved exotic Pearl (EP) were compared with that of the 'purebreds' of the RBC, SLP and EP to 18 weeks of age. 2. The crossbreds of SLP and EP (SLEP) and RBC and EP (RBEP) had higher body weight and efficiency of food utilisation than the local parents. Heterosis was 5.3, 24.3, 1.6 and 1.6% at 0, 6, 12 and 18 weeks of age, respectively, for RBEP and 3.7, 30.8, 11.5 and 8.6% at 0, 6, 12 and 18 weeks of age, respectively, for SLEP. RBEP was 14.5, 98.8, 35.1, and 36.2% superior to RBC at 0, 6, 12 and 18 weeks of age, respectively. SLEP was also 22.0, 98.7, 41.7 and 41.1% superior to SLP at 0, 6, 12 and 18 weeks of age, respectively. Efficiency of food utilisation improved by 20.4% in RBEP and 24.2% in SLEP. The crossbreds were however inferior to EP in terms of weight gain and efficiency of food utilisation. 3. Evidence from this study indicated that crossing the local Pearl guinea fowl with the faster-growing exotic stock is capable of rapidly improving the body weight of the indigenous guinea fowl and hence its usefulness as a source of meat in Nigeria. PMID- 1868372 TI - Genetic variation in the time of oviposition in the laying hen. AB - 1. The distribution of oviposition times in modern layers is relatively narrow. Consequently, in management systems where hens have to compete for nestboxes, some eggs will be laid on the floor. 2. The purpose of this study was to investigate the possibility of using genetic methods to change oviposition time while maintaining a high production rate. 3. The mean oviposition times of 464 hens from three selection lines were calculated using time-of-lay records for every egg laid until the hens reached 51 weeks of age. 4. Heritability estimates for mean oviposition time were high for each of the three lines: 0.38, 0.68 and 0.78. 5. The three lines differed in terms of the genetic correlations between mean oviposition time and certain important production traits. It should, however, be possible to shift the mean oviposition time while maintaining a high production rate. 6. It is suggested that the spread in oviposition times be increased by performing divergent selection for mean oviposition time and by mixing the different genotypes in the same commercial flock, kept on the floor or in other non-cage systems. PMID- 1868373 TI - Response of broiler chickens and turkey poults to food restriction of varied severity during early life. AB - 1. Cobb male (7-d-old) and female (6-d-old) chicks and BUT male and female turkeys (7-d-old), were subjected to food restriction of varying severity for 7, 5, 10 and 7d, respectively. 2. The energy allowance was calculated to support from 0% to 75% of the growth rate typical of species, strain and sex. 3. In male and female broilers kept up to 56 and 50 d, respectively, a high rate of weight gain after the restriction period (refeeding period) overcame the growth retardation attributable to restriction, except in the birds which had been subjected to the most severe regimen. In the mildest regiments, body weights reached slightly higher values than those of the ad libitum-fed controls. Overall food conversion efficiency was significantly improved in males and abdominal fat content was reduced in both sexes, regardless of the severity of restriction. 4. Body weights of male and female turkeys, aged 147 and 112 d respectively, of the groups subjected to the milder (75% growth) restriction, significantly exceeded those of the controls. Food conversion efficiency and meat yield were improved by early-age food restriction but carcase fat was not affected. 5. The results for both species of either sex suggest that a mild food restriction applied at an age of about 1 week and allowing for 60 to 75% of normal growth, may offer an economic advantage over a continuous ad libitum feeding regimen. PMID- 1868374 TI - Muscle protein turnover in chickens selected for increased growth rate, food consumption or efficiency of food utilisation: effects of genotype and relationship to plasma IGF-I and growth hormone. AB - 1. Rates of muscle protein turnover, growth, and food consumption were determined in 4 lines of chickens selected for either weight gain (line W), food consumption (line F), efficiency of food conversion (line E), or at random (line C) and in two Australian commercial broiler strains (S and H). These measures were related to body composition and the circulating concentrations of plasma growth hormone (GH) and IGF-I. 2. N tau-methylhistidine excretion was 10-14% higher in line F and 7-13% lower in line E compared to line C, showing divergence in the rate of muscle protein breakdown with selection. 3. There were no differences between the 4 experimental lines (W, F, E and C) in muscle protein fractional synthesis rates, whether calculated from N tau-methylhistidine excretion or measured directly by 3H-phenylalanine incorporation. 4. No consistent differences were found between lines in circulating concentrations of either GH or IGF-I but plasma IGF-I concentrations were positively correlated over all lines with protein accretion rates. There was a strong inverse correlation over all lines between the rates of protein degradation and FCR. 5. The correlated responses in protein degradation rates are consistent with the notion of a positive genetic association between the overall efficiency of food utilisation for growth and the efficiency of protein metabolism. PMID- 1868375 TI - Supplementation of broiler drinking water with liquid ammonium polyphosphate. AB - 1. In each of two experiments lasting 21 days a commercially available ammonium polyphosphate solution was provided in the drinking water as the sole source of supplemental phosphorus for day-old chicks housed in batteries. 2. In both experiments, similar daily phosphorus intakes either from dicalcium phosphate in the food or from ammonium polyphosphate in the drinking water supported equivalent responses in body weight gains. The same was true for the tibia ash results in experiment 2. 3. Liquid ammonium polyphosphate, while marketed for addition to diets, appears to be also very effective as a waterborne source of phosphorus for broilers. PMID- 1868376 TI - Energy utilisation in germ-free and conventional chicks fed diets containing sorbose. AB - 1. In experiment 1, growing conventional (CV) chicks were fed on diets containing graded amounts (0, 100, 200 and 300 g/kg diet) of sorbose from 4 to 14 d. Protein, fat and energy deposition were determined after carcase analysis. The values for growth, food efficiency, metabolisable energy (ME) and fat and energy depositions declined as the dietary sorbose content increased. 2. In experiment 2, the performances of germ-free (GF) and CV chicks fed on diets with (100 g sorbose/kg diet) or without sorbose were investigated. On both diets, body weight gain, food consumption and protein accumulation in GF chicks were significantly higher than those in CV birds. No significant differences were observed between the dietary treatment except for ME values, which were significantly lower for the sorbose diet. 3. It is suggested that dietary sorbose decreased energy utilisation, and that the microbial contribution to the utilisation of dietary sorbose was negligible in the chicken. PMID- 1868377 TI - Influence of dietary alpha-tocopherol on tocopherol concentrations in chick tissues. AB - 1. The effect of feeding alpha-tocopherol (5 to 180 micrograms/g diet) for 24 days on the concentrations of alpha-tocopherol in various chicken tissues was investigated. 2. Tissue alpha-tocopherol concentrations responded to dietary intake in the order: heart congruent to lung greater than liver greater than thigh muscle greater than brain, and in all cases the relationship between the concentrations of dietary and tissue alpha-tocopherol was highly significant (0.997 less than or equal to r less than or equal to 1). 3. Plasma alpha tocopherol concentration appears to be a good index (r greater than or equal to 0.910, P less than 0.001) of alpha-tocopherol status of lung, liver and heart. PMID- 1868378 TI - Pharmacotoxicological aspects of nitrate and nitrite in domestic fowls. AB - 1. The effects of nitrates and nitrites on growth, erythrocytic count, liver and kidney functions, humoral and cell mediated immune responses in cockerels were investigated. 2. Sodium nitrate (4.2 g/kg diet) and sodium nitrite (1.7 g/kg) retarded growth, caused methaemoglobinaemia and changes in erythrocytic count, serum concentrations of glutamic-pyruvic transaminase, creatinine and urea. 3. Cockerels given nitrate or nitrite in the food had reduced haemagglutination responses after injection of sheep erythrocytes and a reduced delayed hypersensitivity reaction to purified protein derivative tuberculin following sensitisation to Bacille Calmette Guerin. 4. Nitrates and nitrites are environmental pollutants present in food and water and they may contribute to the aetiology of liver and kidney diseases and problems related to failure of immunity in domestic fowls. PMID- 1868379 TI - Influence of thyroidectomy on reproductive responses of male domestic turkeys (Meleagris gallopavo). AB - 1. The influence of age at thyroidectomy on reproductive activity of male turkeys was investigated. 2. Thyroidectomy of 53-week-old male domestic turkeys that had been reproductively active for 25 weeks resulted in undetectable plasma thyroxine concentrations, termination of semen production and testicular regression. Daily light-dark treatment was 14L:10D before and after thyroidectomy. 3. Thyroidectomy of 28-week-old, reproductively inactive, males maintained on a daily light-dark cycle of 8L:16D resulted in increased semen volumes following photostimulation with 14L:10D at 32 weeks of age. Semen quality was not affected, while plasma thyroid hormone concentrations were undetectable. The moult and termination of semen production that occurred in response to changing the daily light-dark cycle from 14L:10D to 8L:16D near the end of the study were inhibited by thyroidectomy. 4. The requirement for the thyroid glands in the reproductive processes of male turkeys changes either with age or after an extended period of reproductive activity. PMID- 1868380 TI - Compartment syndrome. PMID- 1868381 TI - Dormant metastases. PMID- 1868382 TI - Flow cytometry--implications for the surgeon. PMID- 1868383 TI - Protocol for banking bone from surgical donors. PMID- 1868384 TI - Nonoperative management for blunt splenic trauma. PMID- 1868385 TI - An unusual case of tear of spleen. PMID- 1868386 TI - Comparison of mild and deep hypothermia: do they provide similar protection in all neonatal hearts? AB - Despite various techniques of hypothermia it is still difficult to provide optimal myocardial preservation in neonatal cardiac surgery. The early effects of moderate and deep hypothermia were examined in neonatal pig hearts by studying metabolism over time and the tolerance of the hearts to global ischemia. The latter was measured by the time to onset of ischemic contracture, an indicator of irreversible ischemic damage. After control right ventricular biopsies were done, 56, 3-day-old neonatal hearts were excised and placed in one of four temperature regulated baths (37 degrees C, 25 degrees C, 19 degrees C, 12 degrees C). A compliant left ventricular balloon measured onset time to ischemic contracture (TIC) (2 mm Hg increase in pressure). Biopsies were also done at 15 and 30 minutes of ischemia. Progressive hypothermia significantly (p less than 0.001) prolonged TIC but resulted in an increased standard error of the mean (SEM). Lactate accumulation was the least in deep hypothermia (12 degrees C, 19 degrees C) (p less than 0.05) and intermediate with moderate hypothermia (25 degrees C), and all were less (p less than 0.01) than that at normothermia. The decline of adenosine triphosphate was slowed more by hypothermia than normothermia. These observations can be used to improve current methods of myocardial preservation in neonatal hearts. PMID- 1868387 TI - Tumour dormancy: initiation, maintenance and termination in animals and humans. AB - The authors review the natural occurrence of tumour dormancy in man and animal models, which show the importance of cellular defence mechanisms in inducing and maintaining the state of tumour dormancy. Six cases of non-small-cell lung cancer are described. The patients exhibited moderate to very strong delayed hypersensitivity reactions to soluble lung-cancer antigen after specific immunotherapy. Three patients had nonregional metastases at 11, 12 and 14 years. Two had regional recurrence after 9 years, and in one patient a small hilar-node metastasis was found at autopsy after 7.6 years. In each case an immunodepressive event or drug treatment preceded resurgent growth. The effect of renal transplantation in patients with a history of surgery for cancer supports the conclusion that cellular defence mechanisms are crucial for the maintenance of tumour dormancy in man. PMID- 1868388 TI - Cardiac transplantation: treatment for cardiogenic shock. AB - Eighty-six patients received orthotopic cardiac transplants at the Royal Victoria Hospital in Montreal between 1985 and 1989. Of these, 16 mortally ill, being sustained in hospital by the intravenous administration of inotropic agents (15 patients [94%]) or intra-aortic balloon counterpulsation (6 [38%]). There was one early death (at 7 days), for a death rate of 6.3% (versus 8.6% for the 70 "elective" transplants). Two others died of delayed infection: one of viral hepatitis at 6 weeks, and one of pneumonia due to Pneumocystis 4 months after transplantation. The other 13 patients are alive and well 12 to 66 months postoperatively. Nine have returned to their preoperative work, three have decreased activity levels but are functioning well, and one is retired. PMID- 1868389 TI - Small-bowel carcinoid presenting in association with a phytobezoar. AB - An unusual case of a recurrent, postoperative, small-bowel obstruction is presented. The obstruction was due to a phytobezoar proximal to the site of a primary carcinoid of the small bowel. The radiologic findings of a mobile, intraluminal filling defect and a more distal, fixed mural mass are reviewed. The cause of the recurrent obstruction was likely a "ball-valve" effect of the phytobezoar at the site of stenosis caused by the carcinoid. This case emphasizes the value of small-bowel imaging in repeated small-bowel obstruction. PMID- 1868390 TI - The natural history of suspected scaphoid fractures. AB - Clinically suspected scaphoid fractures are common injuries. The authors prospectively followed up, by serial radiography and bone scanning, 23 patients who had a history of trauma to the carpus and associated localized tenderness to the anatomic "snuff box": in 15 patients the radiographs and bone scans were negative; in 5 the radiograph was equivocal and the bone scan positive. The authors concluded that patients with clinically suspected scaphoid fractures and negative radiographs can be treated symptomatically without immobilization in a cast. Patients with equivocal radiographs should be assumed to have a fractured scaphoid and treated accordingly. PMID- 1868391 TI - DNA flow cytometry of large-bowel biopsies showing that adenoma tissue predicts the ultimate nature of the lesions. AB - Ploidy of neoplastic large-bowel cells in lesions from which biopsies showed only adenoma tissue by histopathologic examination was investigated retrospectively by DNA flow cytometry. Biopsy and resected-specimen blocks gave interpretable ploidy profiles from 83 lesions. The expectation that adenomas will show diploidy in biopsies and that adenocarcinomas will show aneuploidy in biopsies was fulfilled in 80% of the lesions. In addition, four lesions with diploid biopsies were polyps with minimal invasion. Thus, diploidy would have correctly predicted that local resection was adequate treatment for 62 lesions and conversely that cancer resection was the appropriate treatment for 8 lesions, for an overall predictive success rate of 87%. In conjunction with endoscopic, radiologic and other data, DNA flow cytometry of biopsies from apparently benign large-bowel lesions could become a useful addition to therapeutic decision-making. PMID- 1868392 TI - [Pathologic study of Morton's neuroma]. AB - The clinical syndrome of Morton's neuroma [correction of nephroma] was described over a century ago, but its etiopathology remains unknown. Recent studies suggest that it may be induced by compression neuropathy. Histologic changes in digital nerves resected for therapeutic purposes were compared with histologic findings of digital nerves sampled at autopsy of asymptomatic subjects. Results show that approximately one-third of resected "diseased" digital nerves were histologically normal. The authors question the therapeutic approach, which consists of resecting the nerves. PMID- 1868393 TI - Compartment syndrome after surgery in the lithotomy position. AB - Compartment syndrome developed in five patients after prolonged surgery in the lithotomy position. Four different surgeons performed the operations. Serious morbidity resulted from the syndrome and could have been prevented by consideration of the factors that predispose to its development: tight bindings; direct pressure on the calves; and prolonged time in the lithotomy position. The pathogenesis of compartment syndrome in this group of patients is discussed. PMID- 1868394 TI - Outpatient orthopedic surgery: a retrospective study of 1996 patients. AB - Outpatient surgical procedures performed at the Centre Hospitalier de l'Universite Laval on 1996 patients (1091 men, 905 women) were studied retrospectively. Lower-limb surgery accounted for 66.5% of the procedures. The mean age of the 1996 patients was 40.7 years. General anesthesia was used in 91.5% of the cases. After surgery, the patients were discharged according to the criteria described by Wetchler and Kortilla. The unanticipated hospital admission rate was 6.3% and the complication rate was 1.3% with no life-threatening conditions. Proper selection and preparation of the patient and strict criteria for safe discharge after day surgery are mandatory for the patient's safety and satisfaction. PMID- 1868395 TI - Is age an independent variable in the morbidity and mortality of patients with colorectal cancer? A prospective study. AB - The authors examine prospectively the results of a single surgeon (H.S.S.), using a computerized database to determine the effect of age on morbidity and mortality in the management of colorectal cancer. Computer input was performed by a nurse data manager (20 minutes per patient), and data retrieval required approximately 30 minutes of computer time. Between 1984 and 1989, 241 patients with primary colorectal cancer underwent operation. The average age was 67.9 years (range from 31 to 94 years). The authors compared 108 (44.8%) patients who were older than 70 years with 133 (55.2%) patients who were 70 years of age or younger. Rectal carcinoma was more common in the younger age group (41.3% v. 20.4%), but right sided carcinoma was more common in the older age group (36.1% v. 19.6%, p less than 0.001). Bleeding was more frequent in the younger patients than in the older ones (51.9% v. 35.2%, p less than 0.01). There was no difference between the two groups in tumour staging, using the modified Dukes' classification. The overall mortality was 2.5% and morbidity was 39.4%, with no significant differences between the groups. The authors conclude that age should not be a determinant in consideration of operation for colorectal cancer and that a personal computerized database facilitates simple prospective studies. PMID- 1868396 TI - Hepatic artery pseudoaneurysms in acute pancreatitis. AB - The authors present a case of multiple intrahepatic pseudoaneurysms complicating acute gallstone pancreatitis, and they review the relevant literature. The complementary roles of ultrasonography, computed tomography and arteriography are illustrated. Although necrotizing vasculitis with resultant aneurysmal changes in peripancreatic vessels is a recognized complication of chronic pancreatitis, similar pseudoaneurysms have rarely been described in association with acute pancreatitis. PMID- 1868397 TI - Appendicular abscess presenting as neoplastic ileocecal obstruction. AB - Most complications after appendectomy occur within weeks of the operation. The authors present a case in which an appendicular abscess presented more than 18 years after appendectomy for acute appendicitis. The abscess simulated a neoplastic obstructive process, and a communication was demonstrated between the cecum and the abscess cavity through the appendiceal stump. PMID- 1868398 TI - Neuroendocrine tumour of the inferior vena cava. AB - Malignant tumours of the inferior vena cava (IVC) are rare. Secondary involvement of the IVC by adjacent retroperitoneal tumours is more common than the occurrence of leiomyosarcomas of the IVC. The authors present a case of a secondary neuroendocrine tumour of the infrarenal vena cava that presented with pulmonary emboli. To their knowledge this presentation has not been reported previously. The tumour was technically resectable and reconstruction of the IVC was not required. No primary tumour was identified. As palliative treatment, an aggressive surgical approach is recommended when the primary tumour is controlled or is not readily identified. PMID- 1868400 TI - Cerebrovascular disorders in the 1990s. PMID- 1868399 TI - Epidemiology of and stroke-preventive strategies for atherothromboembolic brain infarction in the elderly. AB - Age is the most important risk factor for ischemic stroke. The most common cause of ischemic stroke in the elderly is atherosclerosis. Patients who have had a recent transient ischemic attack (TIA) are at high risk for subsequent stroke. Thus far only aspirin and ticlopidine have proven to be effective in preventing stroke. At present, all elderly patients who have had an atherothromboembolic TIA or stroke should receive therapy as well as either aspirin or ticlopidine for control of atherosclerotic risk factors. PMID- 1868401 TI - Asymptomatic carotid artery disease in the elderly. Diagnosis and management strategies. AB - Carotid atherosclerosis is commonly detected in the asymptomatic elderly and in patients with known vascular disease in other distributions. Although there has been considerable interest in carotid bruits, they are not a reliable indicator of asymptomatic stenosis. In patients with asymptomatic stenosis detected by carotid ultrasound or angiography, the annual risk of ipsilateral infarction is approximately 1% to 2%. If ischemic events occur, they are usually transient ischemic attacks. Stroke risk is higher when there is progressive stenosis, stenosis exceeding 75% to 80%, and, possibly, complicated plaque-morphologic characteristics. The treatment of asymptomatic carotid stenosis remains controversial. Antiplatelet agents are of unproven value in asymptomatic patients. The role of surgical management is disputed because of uncertainties regarding the natural history of asymptomatic stenosis and the efficacy and complication rates of endarterectomy. Pending results of several ongoing randomized clinical trials, it may be advisable to withhold endarterectomy from those asymptomatic patients with stenosis of less than 75% to 80%. Prophylactic carotid endarterectomy is not necessary in the patient with asymptomatic stenosis who will undergo another operative procedure such as coronary artery bypass. PMID- 1868402 TI - Cardiogenic stroke in the elderly. AB - Cardiogenic stroke accounts for 15-20% of all ischemic strokes and for more than double than number in the very elderly. In this article, available data regarding cardiogenic embolism, its prevention and management in the elderly are reviewed in addition to the epidemiology, diagnosis, and major sources of cardiac emboli, and nonrheumatic atrial fibrillation. PMID- 1868403 TI - The spectrum of lacunar infarction in the elderly. AB - Lacunar infarcts are small subcortical ischemic brain lesions caused by occlusion of a perforating arteriole. The occlusion results from thickening of the arteriolar wall (arteriolosclerosis), is related to aging, and is accelerated by arterial hypertension. The infarction is usually associated with one of several clinical lacunar syndromes, depending on the exact location of the lesion. Patient evaluation should include the documentation of infarct size and location with imaging studies and the search for uncommon hematologic derangements that predispose to thrombosis. Recovery from a single lacunar infarction is usually very good. Most important in prevention of lacunar infarction recurrence is control of hypertension. Aspirin therapy also appears to be beneficial. PMID- 1868404 TI - Medical management of acute cerebral ischemia in the elderly. AB - Stroke ranks third as a cause of death in much of the industrial world, surpassed only by heart disease and cancer. Thrombotic and embolic arterial occlusions are the leading causes of cerebral infarction. Once a major cerebral infarction has occurred, therapy is limited to the prevention of complications and rehabilitation. Identification and treatment of stroke-prone patients are now not a standard part of medical practice. However, the proper management of the patient with acute cerebral ischemic or progressing stroke is a subject of debate. Treatment of progressing or acute cerebral ischemia is aimed at prevention of infarction in areas of the brain that are still viable. A number of therapeutic strategies are currently being investigated in the management of ischemic stroke. PMID- 1868405 TI - Prevention and management of medical complications of the hospitalized elderly stroke patient. AB - Medical complications may account for 30% or more of the deaths resulting from acute ischemic stroke in the elderly. In descending order of frequency, the most deadly complications are bacterial pneumonia, pulmonary embolism, myocardial infarction, and sepsis without pneumonia (often in the setting of a urinary tract infection or a necrotic decubitus). Normal aging is associated with declining pulmonary and cardiovascular functions as well as declining immunocompetence and physical barriers to infection. The neurological effects of acute ischemic brain injury compound these susceptibilities. Accordingly, a high degree of vigilance is emphasized in the diagnostic and therapeutic guidelines provided for care of the lungs, the heart, the urinary tract, and the skin. Guidelines are also provided for management of blood pressure during the first hours and days following stroke onset. Treatment should be withheld unless specific medical indications are identified. When antihypertensive agents are administered, the appropriate dose may be lower than usually recommended (e.g. labetalol) in order to minimize abrupt drops in blood pressure that may result in further injury to potentially viable ischemic brain tissue. PMID- 1868406 TI - Poststroke seizures in the elderly. AB - Strokes are the most common cause of epilepsy in the elderly. Seizures after an acute stroke have been estimated to occur in 5% to 10% of cases. A distinction between early and late seizures should be made. Early seizures are more common, occur very early in the evolution of the stroke, and tend to be focal motor, brief, and isolated. They are likely to be the result of an acute local brain metabolic alteration induced by the cerebrovascular event, and once these derangements are reversed, seizures disappear. Epilepsy usually does not follow early seizures, but the risk is probably increased. Late seizures occur months to years after the stroke and are probably due to structural brain abnormalities leading to the development of an epileptic focus. The majority of these cases develop epilepsy. The risk of seizures is markedly increased when the cerebrovascular event involves the cerebral cortex. Deep-seated hemispheric or infratentorial lesions rarely produce seizures or epilepsy. It is possible that hemorrhagic stroke carries a higher incidence of seizures, but the issue remains controversial. It has also been suggested that embolic infarction has a higher incidence of seizures that does thrombotic infarction, but definitive evidence is lacking. The presence of seizures in an acute stroke does not seem to correlate with the size of the lesion, functional outcome, or mortality. Prophylactic treatment with antiepileptic drugs is probably not indicated in most types of strokes, except for subarachnoid hemorrhage after a ruptured intracranial aneurysm. When early seizures develop, treatment is indicated but may not be necessary for a prolonged period of time. If late seizures develop, chronic anticonvulsant therapy is recommended. PMID- 1868407 TI - Recognition and management of poststroke depression in the elderly. AB - Depression occurs in 30-50% of stroke survivors and is an important determinant of functional outcome in these patients. Depression after stroke has a biological basis and can be successfully treated. Tricyclic drugs are the first line of treatment therapy but their side effects need to be considered and patients undergoing this treatment need to be carefully monitored. PMID- 1868408 TI - The rehabilitation of elderly stroke patients. AB - Therapies for physical and cognitive impairments and functional disabilities can usually begin within several days of an acute stroke. The geriatric patient challenges the rehabilitation team's assessment and management skills because of the premorbid medical and psychosocial problems of many of the elderly. About 75% of 1-month survivors will walk and 60% will be able to care for themselves with supervision or independently within 3 months. We provide an overview for the common problems in mobility, activities of daily living, communication, nutrition and swallowing, behavior, continence, sexual function and social support that require careful analysis and specific measures to improve the quality of life of the disabled patient. As useful interventions are better defined through prospective, rigorous clinical trials, and as neuro-scientific discoveries about basic neural mechanisms after injury come to be applied, we will see a yet more complete and meaningful recovery of function following stroke. PMID- 1868410 TI - Diagnosis and management of intracerebral hemorrhage in elderly patients. AB - An analysis of the risk factors and clinical presentation of intracerebral hemorrhage in the elderly is provided. Specific pathogenic mechanisms that apply to the elderly, such as cerebral amyloid angiopathy, are discussed in detail. General management of intracerebral hemorrhage is discussed, along with specific issues related to the surgical indications of the various types of intracerebral hemorrhage. PMID- 1868409 TI - Neuro-ophthalmologic vascular emergencies in the elderly. AB - The significance, management and prognosis of several disorders affecting either vision or ocular motility are discussed. Transient and persistent visual loss are common problems in the elderly. Anterior ischemic optic neuropathy is extensively reviewed because of the importance of recognizing forms due to giant cell arteritis, which require urgent treatment with steroids to prevent further visual loss. The various pathologic conditions that can affect the ocular motor nerves in the cavernous sinus are mentioned. The problem of differentiating benign ischemic lesions causing a third nerve palsy from ominous compressive palsies due to aneurysms is addressed, with emphasis on the clues provided by the pupil. PMID- 1868411 TI - Diagnosis and management of nontraumatic subarachnoid hemorrhage in elderly patients. AB - Subarachnoid hemorrhage is a significant problem in the geriatric population. The most common causes of nontraumatic subarachnoid hemorrhage in elderly patients are ruptured aneurysms or arteriovenous malformations. Aggressive therapy for aneurysmal subarachnoid hemorrhage is warranted in many patients whereas conservative treatment of arteriovenous malformations is customarily warranted in this age group. Less common causes of subarachnoid hemorrhage in geriatric patients include tumor bleeding, bleeding diathesis, and systemic illnesses. A number of these considerations must be kept in the differential diagnosis of any subarachnoid hemorrhage in a geriatric patient. PMID- 1868412 TI - Chronic subdural hematoma in the elderly. AB - Elderly individuals may develop an asymptomatic subdural hematoma as a result of minor trauma, anticoagulant therapy, or other factors. A membrane forms around the initial clot, and this membrane becomes the source for many smaller hemorrhages. Because of these rehemorrhages, the hematoma slowly enlarges with time and ultimately becomes symptomatic. The most common symptoms are headache, changes in mentation, and hemiparesis. Chronic subdural hematomas are accurately diagnosed by either CT or MRI, and the treatment consists of surgical evacuation. After successful management, most patients return to their premorbid level of functioning. PMID- 1868413 TI - Vascular dementias in the elderly. AB - In this review, challenging and controversial aspects of vascular dementias in the elderly are examined. Topical discussions underscore diagnostic criteria, epidemiology, clinical syndromes and diagnosis, prognosis and treatment. The need for a reappraisal of dementias with a shift from broad categorization to identification of specific vascular mechanisms that contribute to cognitive impairment and the need for more basic epidemiological studies are highlighted. With this information, a substantial scientifically-based approach to prevention and treatment can be undertaken. PMID- 1868414 TI - Diagnosis and treatment of cerebral amyloid angiopathy. AB - CAA is the infiltration of leptomeningeal and penetrating cortical vessels with amyloid, sparing the subcortical regions and the systemic vasculature. It occurs with increasing frequency after the sixth decade. The major clinical manifestation of CAA is lobar intracerebral hemorrhage, which can be sporadic or hereditary. CAA has also been associated with normal aging, Alzheimer's disease, cerebral infarction, and periventricular demyelination. Biochemical studies have shown that the amyloid deposits in the brains of patients with normal aging, sporadic CAA-associated hemorrhage, hereditary cerebral hemorrhage, and Alzheimer's disease are identical. The exact mechanism by which CAA produces lobar hemorrhages and the role of CAA in the development of dementia are unclear. Biopsy of the involved cerebral cortex and leptomeninges is the only definitive way to diagnose CAA. Acute management of CAA-associated lobar hemorrhage consists of aggressive control of associated hypertension and supportive care. Surgical removal of the hemorrhage has not been shown to improve survival. Antiplatelet and anticoagulant therapy should be avoided in elderly patients with known CAA. PMID- 1868415 TI - Ethical issues in the management of cerebrovascular disease. AB - Medical ethics, as a scholarly and applied discipline, is concerned with the morality of behavior in medical matters. The field of cerebrovascular disease is a worthy paradigm of medical ethical issue. Victims, whether they be patients or their families, are vulnerable, and the ethical virtues of kindness, understanding, compassion, mercy, and justice are badly needed. A variety of hypothetical ethical scenarios faced by the physician are discussed in this article in addition to four actual patient studies with commentary. PMID- 1868416 TI - Mortality in a cohort of patients with schizophrenia: a record linkage study. AB - A retrospective study of mortality was conducted in which 3,623 patients with schizophrenia receiving treatment in Alberta between 1976 and 1985 were followed to the end of 1985. Vital status was determined by record linkage to the Statistics Canada Mortality Data Base. There were 301 deaths in the cohort, 97 of which were due to suicide. For all causes of death combined, the risk of mortality was approximately double that of the Alberta population; for suicide, risk was increased by a factor of 20. Mortality from circulatory, respiratory, digestive and genitourinary diseases was also greater than expected. It is estimated that those who suffer from schizophrenia have a life expectancy which is approximately 20% shorter than that of the general population. This study confirms earlier research demonstrating an increased risk of mortality associated with schizophrenia and extends those findings to specific causes of death. PMID- 1868417 TI - Studies of the effectiveness of day treatment programs for children. AB - Day treatment programs for children are based on the need for more intensive therapeutic treatments for children who do not respond to outpatient programs. Day treatment costs less than hospitalization, does not disrupt family, peer or community ties, and do not result in the child's dependence on them. The authors review studies on the effectiveness of day treatment programs. Findings are discussed and methodological questions are raised for future evaluative research. PMID- 1868418 TI - A cross-cultural study of major depression and family functioning. AB - Patterns of family functioning in families with a depressed member from two cultures (North America and Hungary) were compared. In both cultural settings, families with a depressed member reported poorer family functioning than the control families. Comparisons between the two depressed groups, however, showed that the response to family dysfunction by the two cultures differed. While depressed families in Hungary reported difficulties in setting family rules and boundaries, those in North America experienced impaired functioning in solving problems, communicating, being involved with each other, and in overall functioning. These results are discussed in terms of the interplay between culture, depression and family functioning. PMID- 1868419 TI - Spouse assault on mentally disordered wives. AB - To assess the prevalence and associated features of wife assault in psychiatric patients, 152 married women who had a psychiatric disorder and who were consecutively seen at or admitted to a psychiatric unit were assessed using a structured questionnaire. Forty-nine percent of the patients had been assaulted by their husbands. There was a significant relationship between hospital admission and recent assault. Parental violence and whether or not the husband had a criminal record were strongly related to wife assault. The wives' responses to the assaults were investigated. PMID- 1868421 TI - New uses of countertransference for the inpatient treatment of borderline personality disorder. AB - The author describes the uses of countertransference for the inpatient treatment of borderline personality disorder. Differences from usage in the dyadic outpatient situation are noted. In particular, the countertransference induced in staff may provide a crucial signal function reflecting the patient-ward system. Understanding these feelings provides information not only about the patient's inner world but also about general system features such as the staff's needs, therapeutic capacity and unresolved feelings from previous borderline patients. The signal function may also have diagnostic and treatment implications. A conceptualization of countertransference that encompasses the unique system aspects of inpatient psychiatry is helpful in the care of borderline patients. PMID- 1868420 TI - DSM-III: use of the multiaxial diagnostic system in clinical practice. AB - The authors report on the use of the DSM-III, several years after its introduction, in the clinical diagnosis of 154 subjects with first onset psychosis. Clinicians usually assigned Axis I diagnoses but used the remainder of the multiaxial system less than one time in three; if a standard recording form was in place, the multiaxial system was used more often. Trainees used the DSM III most, followed by psychiatrists affiliated with a university and community based clinicians. Agreement between researchers and clinicians on diagnoses was fair to poor. The authors discuss the implications of the acceptance of the complex diagnostic system in routine clinical practice. PMID- 1868422 TI - The dangerousness criterion for civil commitment: the problem and a possible solution. AB - The dangerousness criterion for civil commitment fails to specify which mental disorders justify commitment. This ambiguity is highlighted by the fact that there are patients with personality disorders or substance abuse who may be dangerous but for whom we have few effective treatments. A possible solution might be provided by adopting the American Psychiatric Association guidelines which consider severity of mental disorder and treatability in its criteria. PMID- 1868423 TI - Psychiatry in the Canadian Correctional Service. AB - This paper traces the development of psychiatric services for offenders suffering from mental disorders within the Correctional Service of Canada from the 19th century to the present day. The major milestone in the development of these services was the report to the Solicitor General of Canada in 1972 entitled "The General Programme for the Development of Psychiatric Services in Federal Correctional Services in Canada (Chalke Report). The report resulted in the development of the regional psychiatric centres, which remain the cornerstone of psychiatric services within the Canadian federal correctional system. Based on the authors' own experiences working at Corrections Canada, the paper endeavours to explore the psychiatric services now being offered and the difficulties remaining. PMID- 1868424 TI - Validation of the five minute speech sample in measuring expressed emotion. AB - The relationship of the Five Minute Speech Sample (FMSS) to the Camberwell Family Interview and its coding system were evaluated. The Camberwell Family Interview and the FMSS were administered to twenty-three relatives of patients diagnosed with schizophrenia. Overall, the results supported the utility of the FMSS and its coding system as a brief screening device for measuring expressed emotion. PMID- 1868426 TI - Loxapine and schizoaffective disorders. PMID- 1868425 TI - Low doses of clonazepam in the treatment of panic disorder. AB - In order to assess the efficacy of a high-potency benzodiazepine in the treatment of panic disorder, an open trial was conducted with clonazepam. Clonazepam was administered in relatively low doses and, after four weeks, was shown to be effective in reducing the number of panic attacks and associated features of the disorder. PMID- 1868427 TI - The public image of psychiatrists. PMID- 1868428 TI - Charles Bonnet syndrome. PMID- 1868429 TI - Parenteral clonazepam for catatonia. PMID- 1868430 TI - Controlling agitation in patients with cognitive impairment. PMID- 1868431 TI - The right to appoint a representative. PMID- 1868432 TI - Manic symptoms associated with the use of captopril. PMID- 1868433 TI - O6-methylguanine-DNA methyltransferase in human normal and tumor tissue from brain, lung, and ovary. AB - The resistance of human tumor strains in culture to cell killing by alkylating nitrosoureas is correlated with their levels of the DNA repair activity O6 methylguanine-DNA methyltransferase. Strains with the Mer- phenotype have no activity and are extremely sensitive. However, the relationship between the sensitivity of human tumors in vivo and transferase levels is not known, and even the existence of Mer- human tumors in vivo has been questioned. In this study 73 human tumor and normal tissue samples from brain, lung, and ovary were assayed for transferase levels and methylpurine glycosylase activity. For each organ, transferase levels varied over 100-fold, and Mer- tumors were detected in each group. There was no correlation between transferase and glycosylase levels, indicating that the absence of transferase in some tumor samples was not an artifact due to necrosis or inactivation of enzymes in the extract. PMID- 1868434 TI - Evidence supporting exclusion of the DCC gene and a portion of chromosome 18q as the locus for susceptibility to hereditary nonpolyposis colorectal carcinoma in five kindreds. AB - Hereditary non-polyposis colorectal carcinoma (HNPCC) syndrome is characterized by early onset and multiple cancers of predominantly the proximal colon and occasionally other organs. The mode of transmission is compatible with autosomal dominant inheritance but the location and characteristics of the putative susceptibility gene are unknown. We performed linkage analyses with the aim of proving or excluding the existence of a susceptibility locus on 18q. This hypothesis was based on the frequent involvement of the DCC gene in colorectal carcinoma and on the previously reported linkage between HNPCC and the Kidd blood group locus (JK) also on 18q. Seven HNPCC families were tested with eight polymorphisms, including three from within DCC. The DCC locus could be excluded as the HNPCC susceptibility locus in five families in which the two point logarithm-of-odds scores were -3.66, -3.63, -4.12, -7.90, and -3.74 at the recombination fraction of 0.00. In the remaining two families linkage could be neither excluded nor confirmed. The added pairwise logarithm-of-odds score for all seven families was -22.65 at the recombination fraction of 0.00. Multipoint analyses of linkage in the seven families suggested exclusion of some 60 cM in the region DCC-D18S18-D18S22-D18S7 as the site for HNPCC susceptibility locus. In addition to DCC, the excluded portion comprises JK. PMID- 1868435 TI - Plasma and cerebrospinal fluid pharmacokinetics of 1-beta-D arabinofuranosylcytosine and 1-beta-D-arabinofuranosyluracil following the repeated intravenous administration of high- and intermediate-dose 1-beta-D arabinofuranosylcytosine. AB - We examined the plasma and cerebrospinal fluid (CSF) pharmacokinetics of 1-beta-D arabinofuranosylcytosine (ara-C) and 1-beta-D-arabinofuranosyluracil (ara-U) in 19 patients with acute leukemia in order to determine whether ara-C or ara-U accumulate in these fluid compartments over time. Plasma and CSF samples were obtained just prior to the conclusion of the first and seventh, and immediately before the second and eighth, 2-h, twice-daily i.v. infusions of 3 g/m2/dose of ara-C (n = 10), 2 g/m2/dose of ara-C (n = 3), and 0.75 g/m2/dose of ara-C (n = 6). There was no accumulation of ara-C in the plasma or CSF, or of ara-U in the plasma following repeated ara-C infusions, ara-U did accumulate in the CSF; the end-dose 1/end-dose 7 CSF ara-U ratio was 0.35 +/- 0.12 and significantly different from this ratio for CSF ara-C (2.10 +/- 3.01; P = 0.004). The end-dose 7 CSF ara-U level was greater than the end-dose 1 CSF ara-U level in all paired specimens. There was a significant correlation between the dose of ara-C administered and the end-dose plasma ara-C and the end-dose CSF ara-U levels (P less than 0.02). One patient who received 3 g/m2/dose of ara-C developed neurotoxicity; his plasma and CSF ara-C and ara-U levels were not extraordinary during the period of ara-C administration, but he had persistent CSF ara-U demonstrable 75 h after his final ara-C dose. CSF ara-U accumulation might underlie the pathophysiology of ara-C-induced neurotoxicity. Intermediate doses of ara-C given i.v. (0.75 g/m2/dose over 2 h) appeared to generate therapeutic CSF ara-C levels and cleared CSF leukemia in one patient. PMID- 1868436 TI - Urinary excretion of degradation products of prostacyclin and thromboxane is increased in patients with gestational choriocarcinoma. AB - Gestational choriocarcinoma metastasizes rapidly, in which process the vasoactive prostanoids may be significant. We therefore compared the urinary excretion of prostacyclin and thromboxane A2 (TxA2) metabolites in 19 women with gestational choriocarcinoma and 20 healthy age-matched women by assessing spot urine samples for 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and 2,3-dinor-6-keto prostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha) (degradation products of prostacyclin) as well as for thromboxane B2 (TxB2) and 2,3-dinor-TxB2 (degradation products of TxA2) by high-pressure liquid chromatography, followed by radioimmunoassay; the data were related to urinary creatinine concentration. The urinary output of 6-keto-PGF1 alpha [29.56 +/- 7.0 versus 25.08 +/- 3.91 ng/mmol creatinine (SE)] in patients with choriocarcinoma was normal, but that of 2,3-dinor-6-keto-PGF1 alpha in cancer patients was higher than in controls (24.44 +/- 5.20 versus 14.84 +/- 1.94, P less than 0.02), as was that of TxB2 (22.72 +/- 4.69 versus 9.69 +/- 1.52, P less than 0.001) and 2,3-dinor-TxB2 (114.21 +/- 30.81 versus 51.81 +/- 10.40, P less than 0.01). The ratio of net prostacyclin output (6-keto-PGF1 alpha plus 2,3-dinor-6-keto-PGF1 alpha) to the net TxA2 output (TxB2 plus 2,3-dinor-TxB2) in cancer patients [0.52 +/- 0.1 (SE)] was lower (P less than 0.03) than in the controls (0.83 +/- 0.1), and in an inverse relation (r = -0.54, P less than 0.05) to the scoring index of poor prognosis for the disease. We conclude that the prostanoid excess in gestational trophoblastic disease, as evidenced for the first time in this study, may originate from choriocarcinoma cells, or may be a paraneoplastic phenomenon, and we conclude also that TxA2 excess may contribute to the tumor growth and/or formation of metastases. PMID- 1868437 TI - Elevated plasma platelet-derived growth factor B-chain levels in cancer patients. AB - Platelet-derived growth factor (PDGF) is produced by a variety of normal and tumor cells in vitro. We have developed an enzyme-linked immunosorbent assay for the detection of the B-chain of PDGF. This assay can reliably detect 0.1 ng/ml of homodimeric recombinant PDGF B-chain and does not cross-react with recombinant PDGF-AA, epidermal growth factor, basic fibroblast growth factor, or transforming growth factor-beta. Citrated plasma from 72 control individuals had a PDGF B chain (PDGF-B) level of 0.32 +/- 0.14 ng/ml (mean +/- SD) with a range of 0.10 0.69 ng/ml. The plasma platelet factor 4 (PF4) level was 97 +/- 70 ng/ml, with a range of 34-363 ng/ml. Citrated plasma was obtained from 131 cancer patients, and plasma PDGF-B was elevated in 19 (15%) of the patients. Both PDGF-B and PF4 were elevated in 14 (11%) of these patients, consistent with a platelet source of PDGF B. In 5 patients (4%), however, PDGF-B was elevated and PF4 was not elevated compared to the control group. This last group of patients may have a tumor derived source of PDGF-B which could be important in autocrine or paracrine growth stimulation of the tumor cells. PMID- 1868438 TI - Potentiation of the cytotoxic action of mafosfamide by N-isopropyl-p formylbenzamide, a metabolite of procarbazine. AB - Several mouse aldehyde dehydrogenases catalyze the detoxification of aldophosphamide, the pivotal metabolite of the prodrugs cyclophosphamide, mafosfamide, and other oxazaphosphorines. N-Isopropyl-p-formylbenzamide, a major metabolite of procarbazine, was found to be an excellent substrate (Km = 0.84 microM) for at least one of these enzymes, namely, mouse aldehyde dehydrogenase 2. The Km for mouse aldehyde dehydrogenase-2-catalyzed detoxification of aldophosphamide is 16 microM. Thus, competition between N-isopropyl-p formylbenzamide and aldophosphamide for the catalytic site on the enzyme should strongly favor the former, and the rate at which aldophosphamide is detoxified should be markedly retarded. Mouse L1210/OAP and P388/CLA leukemia cells are relatively insensitive to the oxazaphosphorines because they contain large amounts of mouse aldehyde dehydrogenase-2. As predicted, N-isopropyl-p formylbenzamide markedly potentiated the cytotoxic action of mafosfamide against these cells. Mouse L1210/0 and P388/0 lack the enzyme. Again as expected, N isopropyl-p-formylbenzamide essentially did not potentiate the cytotoxic action of mafosfamide against these cells. Certain mouse and human hematopoietic progenitor cells also contain an aldehyde dehydrogenase that catalyzes the detoxification of aldophosphamide, but the specific identity of this enzyme remains to be established. N-Isopropyl-p-formylbenzamide potentiated the cytotoxic action of mafosfamide against these cells as well. Clinically, procarbazine and the oxazaphosphorines are used to treat certain neoplastic diseases. Frequently, they are used in combination. Our findings demonstrate the potential for both desirable and undesirable drug interactions when these agents are used concurrently. Similar drug interactions can be expected when other substrates for, or inhibitors of, the relevant aldehyde dehydrogenases, e.g., chloramphenicol, chloral hydrate, and methyltetrazolethiol-containing cephalosporins, are co-administered with the oxazaphosphorines. PMID- 1868439 TI - Establishment and characterization of a mouse monoclonal anti-fucosylceramide antibody, PC47H. AB - A novel mouse monoclonal anti-fucosylceramide antibody was established by using neutral glycolipids from a human pancreas cancer tissue as the immunogen. Mice were immunized with the neutral glycolipids in the form of liposome-containing lipid A. Mouse monoclonal antibodies were screened with enzyme-linked immunosorbent assay and by thin layer chromatography-immunostaining. The latter technique showed that a mouse monoclonal antibody, designated PC47H, specifically reacts with a ceramide-monoglycoside fraction of the neutral glycolipids. The effects of various monosaccharides on the reactivity of PC47H with the neutral glycolipids were tested, and it was found that only fucose was able to inhibit the binding of PC47H to the neutral glycolipids. We also examined the direct binding activity of PC47H against galactosylceramide, glucosylceramide, fucosylceramide, and ceramide. This showed that the antigen specificity of PC47H was exclusively directed against fucosylceramide. In thin layer chromatography immunostaining experiments with neutral glycolipids prepared from various human tissues, we observed that fucosylceramide was highly expressed in human colon and gastric cancer tissues. PC47H recognized the human adenocarcinoma cell lines of colon, stomach, pancreas, and lung but did not react with other tumor cells or with several nontumorous human cells. PMID- 1868440 TI - Anthracycline immunoconjugates prepared by a site-specific linkage via an amino dextran intermediate carrier. AB - Anthracycline, either daunomycin or doxorubicin, was site specifically attached to the carbohydrate moiety of a monoclonal anticarcinoembryonic antigen antibody by using amino-dextran as the intermediate carrier. The reaction resulted in an immunoconjugate that contains approximately 20 to 25 molecules of drug per molecule of immunoglobulin G. Flow-cytometric studies revealed the retention of the antibody-binding activity. The immunoconjugate was cytotoxic to the target cells, as examined by the 75selenomethionine incorporation studies, and remained efficient for targeting a human colonic tumor (GW-39) in the nude mouse model. The conjugate possessed a greater antitumor activity against the subcutaneous tumor than either the free drug or an irrelevant antibody conjugate, and it was well tolerated by the animals at a much higher dose level than was the unconjugated drug. PMID- 1868441 TI - Clinical results and characterization of tumor-infiltrating lymphocytes with or without recombinant interleukin 2 in human metastatic renal cell carcinoma. AB - A Phase I trial of tumor-infiltrating lymphocytes (TIL) expanded in vitro and administered on Days 1 and 8, with or without continuous infusion recombinant interleukin 2 (rIL-2) in 25 patients with metastatic renal cell carcinoma, was conducted. Eighteen of the 25 eligible patients were treated with TIL and escalating doses of rIL-2 (0.0, 3.0, 4.5 x 10(6) units/m2) on Days 1 to 5 and 8 to 12. Dose-limiting toxicity was pulmonary, and the maximum tolerated dose of rIL-2 was 3.0 x 10(6) units/m2. No clinical responses were observed. Immunological monitoring of peripheral blood lymphocytes demonstrated significant increases in CD3+ and CD56+ cells, including the activated T-cell subsets. Phenotypic analysis of cultured TILs demonstrated significant heterogeneity and the presence of CD3+CD4+ and CD3+CD8+ T-cells, with CD3-CD56+ and CD3+CD56+ populations also present. The majority of cultured TILs expressed HLA-DR and CD45RO, with a variable number expressing CD25. The rIL-2-expanded TILs possessed cytotoxicity against allogeneic and autologous tumor, with cytolytic activity against only autologous tumor seen in one patient. Results demonstrate that in vitro expansion of TILs is possible, but further studies are needed to define the biology of TILs in renal cancer and to isolate and expand tumor-specific T-cells. PMID- 1868442 TI - Improved pharmacokinetics and tumor localization of immunotoxins constructed with the Mr 30,000 form of ricin A chain. AB - The two naturally occurring forms of ricin A chain, Mr 33,000 and Mr 30,000 (RTA33 and RTA30) have been purified, and their chemical compositions, toxicities, and tissue distributions have been determined. As reported previously, the in vitro and in vivo toxicities of RTA30 and RTA33 are similar. However, RTA30, which contains less carbohydrate with a lower mannose content than RTA33, accumulated less in the liver than did RTA33. Monoconjugate immunotoxins (i.e., containing one RTA per monoclonal antibody molecule) were constructed between RTA30 or RTA33 and the antitumor monoclonal antibody 791T/36, which recognizes a Mr 72,000 antigen on osteosarcoma and colon carcinoma cells. The two immunotoxins had similar cytoxicities in vitro but differed substantially in their pharmacokinetics and tissue distributions in vivo in nude mice bearing C170 human colorectal carcinoma xenografts. The immunotoxin derived from RTA30 (IT30) accumulated less in the liver than the immunotoxin derived from RTA33 (IT33) and cleared more slowly from the blood; the alpha and beta half-lives for IT30 and IT33 were 0.50 and 20.5 versus 0.17 and 14.6 h, respectively. As a probable consequence, IT30 accumulated to approximately 3-fold higher levels in the C170 xenografts than IT33. The reduced clearance of IT30 by the reticuloendothelial system thus resulted in prolonged survival in the blood and enhanced tumor localization relative to IT33. PMID- 1868443 TI - Preferential expression of the dbl protooncogene in some tumors of neuroectodermal origin. AB - We have investigated the expression of the dbl protooncogene in a wide variety of human tumors of different embryological derivation. We found that proto-dbl mRNA could be detected preferentially in a few neoplastic histiotypes of neuroectodermal origin. The common, normal 5-kilobase size of the proto-dbl transcript detected indicated that the proto-dbl in these tumors was not rearranged. These data, in agreement with our previous reports, suggest that the dbl protooncogene is expressed in a highly tissue-specific manner and indicate that this gene may be involved in the growth and differentiation of some cells of neuroectodermal origin. PMID- 1868444 TI - Effect of starch malabsorption on fecal bile acids and neutral sterols in humans: possible implications for colonic carcinogenesis. AB - Epidemiological and experimental studies indicate a strong association between an elevated colon cancer risk and increased fecal excretion of secondary bile acids, neutral sterols, and prolonged gastrointestinal transit time. Starch malabsorption, on the other hand, has been reported to be a possible protective factor in colon carcinogenesis. To study the impact of starch malabsorption on these parameters, 12 healthy volunteers consumed a diet rich in starch for two 4 week periods. During a double-blind crossover trial they received the alpha glucosidase inhibitor acarbose (BAY g 5421) in one of the study periods and placebo in the other. During acarbose treatment stool wet weight increased by 68%, stool dry weight by 57%, and gastrointestinal mean transit time by 30%. Fecal concentrations (mg/g dry weight) of the neutral sterols coprostanol, coprostanone, campesterol, 4-cholesten-3-one, and beta-sitosterol decreased by 36.8, 48.7, 42.1, 34.6, and 39.4%, respectively, under acarbose. Concentrations of the major secondary bile acids, deoxycholic and lithocholic acid, decreased by 59.9 and 52.2%, respectively. In spite of an increased stool weight, also daily excretion (mg/day) of these two bile acids was lower under acarbose (47.9 and 36.6%, respectively) compared to placebo, whereas excretion of the main primary bile acid, cholic acid, rose from 22.58 mg/day to 379.80 mg/day during the acarbose period. The changes in fecal bile acid and neutral sterol excretion found during acarbose treatment may explain a protective effect of starch malabsorption on colon cancer development. PMID- 1868445 TI - Natural killer target molecules associated with the transformation of the oncogene-transfected fibroblast. AB - Cell surface antigens, the expression of which is highly enhanced along with the transformation of cells, were analyzed. W14 and W31, EJ-ras oncogene-induced transformants of a WKA rat fetus-derived fibroblast WFB, strongly expressed several transformation-associated antigens as defined by monoclonal antibodies 109, 061, and 081. These monoclonal antibodies recognized Mr 86,000, 62,000, and 101,000 molecules, each composed of a single polypeptide chain. The expression of these transformation-associated antigens was negligible on parental WFB cells. Transforming growth factor-beta could enhance the expression of all of these transformation-associated antigens, but platelet-derived growth factor could only enhance the Mr 86,000 kd molecule expression. In the cytotoxicity assays, poly I:C-induced rat splenic NK cells were cytotoxic to W14 and W31, but not to WFB. The data also showed that the cytotoxicity by these NK cells against NK-sensitive YAC-1 cells was absorbed with the addition of W14, W31, platelet-derived growth factor, or transforming growth factor-beta-stimulated WFB cells. This indicates that NK cells may recognize common target antigens that are expressed among these target cells. It was also indicated that Mr 86,000 and 62,000 molecules were strongly involved in this cytotoxicity, possibly as the target antigens, since F(ab')2 fragments of monoclonal antibodies 109 and 061 strongly inhibited the cytotoxicity. The addition of monoclonal antibody 109, but not 061, inhibited the cytotoxicity even at 60 min after mixing with the effector and target cells, suggesting that the Mr 86,000 molecule may participate in the lethal hit phase of cytotoxicity by NK cells. These data may indicate that some, but not all, transformation-associated antigens are virtually important in the antitumor surveillance mechanisms by the host effector cells, such as NK cells. PMID- 1868446 TI - Tumor cytolysis by lymphocytes infiltrating ovarian malignant ascites. AB - Tumor-associated lymphocytes (TAL) were isolated from the ascitic fluid of patients with adenocarcinoma of the ovary. These cells proliferated and expanded by 100-600-fold as either CD3+ CD4+ or CD3+ CD8+ cultures in the presence of moderate concentrations (50-200 cetus units/ml) of recombinant interleukin 2 and reached high numbers (5 x 10(8)-1 x 10(9)). After expansion of 16 TAL samples from 15 patients, 5 of the 7 isolated ovarian cytotoxic T-lymphocyte cell lines of T-cell receptor (TCR) (alpha beta)+ CD3+ CD8+ CD4- phenotype exhibited preferential cytolytic activity against autologous tumor targets and significantly lower cytolytic activity against allogeneic tumor targets and the natural killer-sensitive cell line K562. The cytolytic activity of the CD8+ TAL was inhibited by operationally anti-TCR (alpha beta) monoclonal antibody and monoclonal antibody specific for the CD3 differentiation antigen, indicating that the TCR and CD3 are involved in the cytolytic process. The other TAL cultures demonstrated similar cytolytic activity against both autologous and allogeneic tumors. The phenotype of these TAL was predominantly TCR (alpha beta)+ CD3+ CD4+ CD8-. Certain CD3+ CD8+ T-cell clones isolated from representative TAL exhibited preferential autologous tumor-specific cytotoxicity that may be major histocompatibility complex restricted. Other CD3+ CD8+ and CD3+ CD4+ clones exhibited nonmajor histocompatibility complex restricted cytotoxicity. These results demonstrate that CD3+ CD4+ and CD3+ CD8+ T-cells present in the ovarian malignant ascites can be propagated in large numbers and for long time intervals as T-cell lines in vitro. This finding may be significant for further investigation of ovarian tumor-specific cytotoxic T-lymphocytes and future adoptive specific immunotherapy studies. PMID- 1868447 TI - Expression of three major protein kinase C isozymes in various types of human leukemic cells. AB - We examined the levels of protein kinase C (PKC) activity and the expressions of its three major isozymes, designated types I (gamma), II (beta), and III (alpha), in the cytosol and particulate fractions of cells from patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL), in an attempt to elucidate the cell type- or lineage specific expression of these isozymes. The levels of PKC activities in the cytosol and particulate fractions from AML cells were higher than those from ALL or CLL cells. The average PKC activities of AML cells, ALL cells, and CLL cells were 18.7, 12.2, and 11.3 pmol/min/10(8) cells, respectively, in the cytosol fractions and 4.4, 3.1, and 2.6 pmol/min/10(8) cells, respectively, in their particulate fractions. M1 cells (French-American-British classification) and AML cells with T-lymphocyte-associated surface antigens, such as CD2 and CD7, had significantly lower PKC activities among AML cells. Immunoblot analyses using monoclonal antibodies against each isozyme revealed that all three isozymes were broadly distributed on leukemic cells with considerable variability in the level of expression. All lymphoid leukemic cells expressed PKC-gamma in the cytosol fractions, albeit a minor component; however, this type was observed in cells from only half the number of AML patients. Those AML cells with cytosolic PKC gamma usually expressed lymphoid surface antigens, such as CD2, CD7, and CD19. On the other hand, cytosolic PKC-beta and PKC-alpha were commonly observed in all types of leukemic cells. AML cells expressed these two types at almost equal levels, but in lymphoid cells, expressions of PKC-beta were usually more abundant than those of PKC-alpha. These data suggest that AML cells with lymphoid antigens might have a lower PKC activity but more predominant expression of cytosolic PKC gamma than the usual AML cells. PMID- 1868448 TI - Levels of p53 protein increase with maturation in human hematopoietic cells. AB - Transfection of the wild-type p53 gene into malignant cell lines usually results in an inhibition of proliferation. However, the physiological function of the endogenous p53 gene product has been difficult to ascertain. In order to examine whether p53 is involved in the regulation of proliferation and/or differentiation of hematopoietic tissue, we modified a recently developed flow cytometric assay to assess p53 protein expression in normal human hematopoietic cells, primary leukemias, and selected leukemia cell lines. In normal human bone marrow, p53 protein was not detected in the proliferative, progenitor cell populations identified by the cell surface antigens CD34 (progenitor cells of multiple lineages) or glycophorin (erythroid precursors). In contrast, low but detectable levels of p53 protein were observed in the nonproliferative, mature lymphoid, granulocytic, and monocytic cell populations. Similarly, p53 levels increased and DNA synthesis decreased during 12-O-tetradecanoylphorbol-13-acetate-induced differentiation of ML-1 myeloblastic leukemia cells. Both of these results suggest that endogenous, wild-type p53 protein may play a role in hematopoietic cell maturation, possibly by contributing to the inhibition of proliferation that occurs during terminal differentiation. Leukemia cells deviated from this pattern of expression: (a) in contrast to the normal, proliferative bone marrow progenitor cells, a significant percentage of patient leukemia samples expressed detectable levels of p53 protein; and (b) leukemia cell lines exhibited lineage specific abnormalities in p53 expression, with overexpression in lymphoid cell lines and lack of expression in myeloid cell lines. PMID- 1868449 TI - Cellular glutathione and thiol measurements from surgically resected human lung tumor and normal lung tissue. AB - Cellular glutathione (GSH) levels were measured from 27 human lung tumor biopsies, enzymatically disaggregated, and compared with cells isolated from normal lung of the same patients. GSH levels from normal lung were similar among patients with a mean value of 11.20 +/- 0.58 (SEM) nmol GSH/mg protein (24 patients) with a range from 6.1 to 17.5 nmol GSH/mg protein. GSH levels varied considerably within and across histological tumor types with the following values: adenocarcinomas, 8.83 +/- 0.96 nmol/mg protein (8 patients); large cell carcinomas, 8.25 +/- 2.51 nmol/mg protein (3 patients); and squamous cell carcinomas, 23.25 +/- 5.99 nmol/mg protein (8 patients). The cyclic GSH reductase assay gave only average GSH values and could not distinguish possible GSH variation among subpopulations of cells isolated. Cell volume measurements and microscopic evaluation of cells isolated from both tumors and normal lung revealed heterogeneity with respect to cell types present. To determine the extent of thiol variation among tumor cell subpopulations, tumor cell suspensions were stained with the thiol-specific stain, monochlorobimane (MCB). The accuracy of MCB staining was tested by flow cytometric analysis of 12 in vitro human tumor cell lines and 3 rodent cell lines. A linear relationship was found between the bimane cellular fluorescence and the cyclic GSH reductase assay for cell lines having less than 80 nmol GSH/mg protein (R2 = 0.82). Above 80 nmol GSH/mg protein the rate of change of the bimane fluorescence intensity with respect to increasing GSH concentrations was much reduced. However, by labeling cells with MCB it was possible to distinguish between cell lines with low versus high GSH content. MCB staining of tumor samples revealed multiple populations of cells with respect to thiol levels. In particular, 2 of 8 squamous cell carcinomas had a proportion of cells with elevated fluorescence intensities (from 10 to 35% of the population) suggesting the presence of cells with greatly elevated thiol levels. These findings underscore the complexity of quantitating intracellular GSH levels from tumor biopsies. The combined use of MCB with flow cytometry and conventional GSH assays may help to delineate subpopulations of cells within tumors with different thiol levels. PMID- 1868450 TI - Structure and expression of the c-sis gene and its relationship to sporadic meningiomas. AB - A deletion in an Alu repetitive sequence in the fifth intron of the c-sis gene of meningioma patients was previously described (M. Smidt et al., J. Clin. Invest., 86:1151-1157, 1990). The authors analyzed the structure of this intron in DNA from peripheral blood leukocytes and tumor samples of 86 patients with sporadic meningiomas. After amplifying these DNA sequences by the polymerase chain amplification reaction, the authors failed to find any cases with deletions. They also analyzed the effects on the expression of c-sis of the fifth intron with or without the deletion. A c-sis expression clone with an SV40 promoter was modified by adding introns 4, 5, and 6, and the resulting clones were used to examine the expression of c-sis mRNA in A172, NIH3T3, and Cos-7 cells. Northern blots showed that the quantity of message was not changed when the introns were present and that the size of the message was not changed by the deletion in the fifth intron. The effect of the fifth intron Alu sequence on the c-sis promoter was also tested using clones with chloramphenicol acetyltransferase as a reporter gene in A172 and Cos-7 cells. The c-sis promoter was not affected by the fifth intron Alu sequence with or without the deletion and in either orientation. There were also no effects when cells were stimulated by phorbol 12-myristate 13-acetate or the regulatory gene Tax from human T-lymphotropic virus type 1. These data do not support a role for deletions in the fifth c-sis intron in the development of most sporadic meningiomas. PMID- 1868452 TI - K-ras mutations in 1,2-dimethylhydrazine-induced colonic tumors: effects of supplemental dietary calcium and vitamin D deficiency. AB - Recent studies from our laboratory have demonstrated that dietary supplemental calcium had no significant effect on the incidence of 1,2-dimethylhydrazine induced colonic tumors, but did decrease the number of rats with multiple tumors and reduced tumor size. Moreover, concomitant vitamin D deficiency appeared to abolish these protective effects of calcium on colonic tumors in this experimental model. To date, however, the mechanism(s) involved in these phenomena remain unclear. In order to address these important issues, 1,2 dimethylhydrazine-induced colonic tumors from animals on control, Ca(2+) supplemented, vitamin D-sufficient, and Ca(2+)-supplemented, vitamin D-deficient diets were examined for the presence of ras oncogene mutations. DNA was extracted from each of these tumors. Targeted areas of K-ras and H-ras genes were amplified by the polymerase chain reaction and analyzed for point mutations using allele specific oligonucleotide hybridization and subsequent DNA sequencing. The results of these studies demonstrated that: (a) approximately one-third of 1,2 dimethylhydrazine-induced colonic carcinomas in the control group had K-ras G to A mutations; (b) no mutations, however, were detected in the cancers of the calcium-supplemented group; (c) concomitant vitamin D deficiency abolished the antimutagenic effect of dietary calcium supplementation (e.g., approximately one third of cancers in this group again had detectable K-ras mutations); and (d) no H-ras point mutations were detected in colonic tumors from any group. These findings suggest that alterations in K-ras mutations may be one possible mechanism by which calcium and vitamin D status influence colonic carcinogenesis in this experimental model. PMID- 1868451 TI - Expression of the diphtheria toxin A-chain coding sequence under the control of promoters and enhancers from immunoglobulin genes as a means of directing toxicity to B-lymphoid cells. AB - Previous results have shown that cells can be killed by the expression of an introduced gene encoding diphtheria toxin A-fragment (DT-A) and that killing can be targeted using tissue-specific transcriptional regulatory elements. Here, we describe expression plasmids containing the DT-A gene linked with promoters and enhancers from immunoglobulin heavy chain or kappa-light chain genes. When these plasmids were transfected into cultured cells, DT-A was expressed in B-lymphoid cells but not detectably in HeLa cells or fibroblasts. A high specificity for B cells was confirmed by assaying for luciferase reporter gene expression from a plasmid containing an analogous combination of immunoglobulin heavy chain regulatory elements. A plasmid containing an immunoglobulin-kappa promoter and enhancer was substantially less active in expressing DT-A in a pre-B-cell line than in B-lymphoma cells, suggesting the possibility of targeting DT-A expression to mature, malignant B-cells while sparing normal B-cell progenitors. By means of viral delivery vehicles, the constructs described might be applied in gene therapy for B-cell leukemias or lymphomas. PMID- 1868453 TI - Chemical engineering of the monoclonal antibody A7 by polyethylene glycol for targeting cancer chemotherapy. AB - The murine monoclonal antibody A7 (Mab A7) against human colon cancer was chemically modified with methoxypolyethylene glycol (PEG) (Mr 5000). A high substitution of PEG molecules on Mab A7 produced a progressive reduction in antibody-binding activity. The pharmacokinetic and immunological properties of PEG-modified monoclonal antibody A7 (Mab A7) and the PEG-modified F(ab')2 fragment, which retained their antibody-binding activity, were assessed and compared with the parent Mab A7 and the parent F(ab')2 fragment. Blood clearance of PEG-modified antibodies appeared to be diminished by PEG modification and was fitted by a two-compartment model. Low PEG-substituted Mab A7 showed less organ uptake in the liver and spleen and similar uptake in the lung and kidney, compared with the parent Mab A7. PEG-F(ab')2 showed less uptake in the liver and kidney. Both preparations exhibited less tissue:blood ratios in all resected organs as compared with parent antibodies. Tumor localization was enhanced by PEG modification for the F(ab')2 fragment, but not by PEG modification for the whole Mab A7. Multiple i.v. administration of PEG-modified antibody to rabbit did not appear to elicit a measurable immune response to the antibody portion of the conjugate. In conclusion, PEG-modified antibodies are promising reagents as drug carriers to the target tumor. PMID- 1868454 TI - Monensin in lipid emulsion for the potentiation of ricin A chain immunotoxins. AB - The utilization of carboxylic ionophores such as monensin for immunotoxin potentiation may be hampered by the poor solubility and short in vivo half-life of these highly lipophilic compounds. Therefore, the use of monensin formulated in a lipid/water emulsion was investigated for the in vitro and in vivo potentiation of immunotoxins. Monensin in emulsion or in buffer was equally effective for the in vitro potentiation of the cytotoxicity of both anti-human transferrin receptor and anti-carcinoembryonic antigen immunotoxins against target cells. In mice, buffer and lipid emulsion were compared as vehicles for the i.p. administration of monensin. The half-life of monensin in the peritoneal cavity of BALB/c x DBA/2 F1 (CD2F1) mice was increased 20-fold by inclusion in lipid emulsion (13 min versus 0.75 min). Treatment i.p. with anti-human transferrin receptor immunotoxin or anti-carcinoembryonic antigen immunotoxin and monensin emulsion prolonged the survival of mice with macroscopic i.p. tumor xenografts of H-Meso-1 mesothelioma and LS174T colorectal carcinoma (200-250% increased length of median survival). The in vivo antitumor effect of the cell specific immunotoxin plus monensin emulsion was superior to immunotoxin alone or to immunotoxin plus monensin in buffer (P less than 0.03; Mann-Whitney U test). This indicates that delivery of monensin in preformed lipid emulsion may produce a reservoir effect of the ionophore in the peritoneal cavity of tumor-bearing mice. Nonspecific control immunotoxin plus monensin emulsion produced no increase in survival. Long-term tumor-free survival (greater than 150 days versus a median survival of 25 days for controls) of mice bearing microscopic LS174T xenografts was obtained by treatment with anti-human transferrin receptor immunotoxin plus monensin emulsion. Administration of either monensin in buffer or monensin in emulsion without immunotoxin had no significant effect on survival. Monensin in this pharmacologically available form significantly improved the in vivo efficacy of both anti-human transferrin receptor immunotoxin and anti-carcinoembryonic antigen immunotoxin when used as regional therapy. PMID- 1868455 TI - Effects of thyroid hormone on androgen- or basic fibroblast growth factor-induced proliferation of Shionogi carcinoma 115 mouse mammary carcinoma cells in serum free culture. AB - DNA synthesis of SC-3 cells cloned from mouse mammary carcinoma (Shionogi carcinoma 115) was remarkably enhanced by androgen as well as basic fibroblast growth factor (bFGF) at the early phase (days 1-3) of stimulation in serum-free culture condition. However, bFGF-induced DNA synthesis could not be observed at the late phase (days 4-6) of stimulation while androgen was able to continuously elicit DNA synthesis. When the effect of androgen on cell yield was examined, the cell number was increased while bFGF could not enhance cell growth. Androgen induced heparin-binding growth factor partially purified from conditioned medium behaved like bFGF in terms of DNA synthesis and replication in SC-3 cells. SC-3 cells were found to contain the high-affinity binding site toward triiodothyronine. The dissociation constant and the maximum number of the binding sites were 7 x 10(-10) M and 1800/cell, respectively. Triiodothyronine significantly blunted the testosterone-induced DNA synthesis. On the other hand, bFGF-enhanced DNA synthesis was not substantially inhibited by triiodothyronine. These results suggest that androgen, but not bFGF, has unique action site(s) which might be important for SC-3 cell replication and might be antagonized by thyroid hormone. PMID- 1868456 TI - A proposed common mechanism by which phorbol esters and epidermal growth factor delay the progression from G2 phase to mitosis of HeLa cells through phospholipid metabolites. AB - The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA; also called phorbol myristate acetate) and epidermal growth factor both rapidly inhibit the transition of HeLa cells from G2 phase to mitosis in a reversible fashion with characteristics of a receptor-mediated response. It was proposed that an intracellular mediator was responsible for this inhibition. In searching for a common mediator elicited by the action of both ligands, the time course of generation of phospholipid metabolites was compared with the cell cycle response of the G2 cohort monitored by time lapse analysis. The time course and the degree of mobilization of diacylglycerols (DG) effected by TPA and by epidermal growth factor and that of phosphatidic acid correlated to a great extent with the onset and the duration of the G2 inhibition caused by both agonists. Further evidence for the proposed role of DGs and/or phosphatidic acid was obtained by the observation that membrane-penetrating 1,2-DG inhibited HeLa cells in G2 phase directly. The concentration of DG required correlated with that elicited by TPA or epidermal growth factor metabolically. This cellular response to 1,2-DG was also seen in cells after down-regulation of protein kinase C using TPA. The data indicate that cellular DG and/or phosphatidic acid may contribute to a restriction of cells in G2 phase possibly by changing membrane properties. PMID- 1868457 TI - Stimulation of apolipoprotein D secretion by steroids coincides with inhibition of cell proliferation in human LNCaP prostate cancer cells. AB - Although steroid hormones are known to play a predominant role in the regulation of cell growth in hormone-sensitive cancers, their mechanisms of action, especially their interaction with growth factors and/or growth inhibitors, is poorly understood. We have recently observed that the effects of androgens and estrogens on the expression of the major protein found in human breast gross cystic disease fluid, protein-24, are opposite to their respective action on cell proliferation in human breast cancer cell lines. Somewhat surprisingly, the recent elucidation of the amino acid sequence of this progesterone binding protein reveals that this tumor marker is apolipoprotein D (apo D), a member of a superfamily of lipophilic ligand carrier proteins. The present study was designed to determine whether apo D is secreted by human prostate cancer cells and could thus be a new marker of steroid action in these cancer cells, and whether the sex steroid-induced stimulation of apo D secretion coincides with inhibition of cell proliferation. We took advantage of the biphasic pattern of the effect of steroids on the proliferation of the human prostate cancer LNCaP cell line, which offers the opportunity to discriminate between positive and negative steroid receptor-regulated cell growth processes. A 10-day exposure to low concentrations of dihydrotestosterone and testosterone caused a potent stimulation of LNCaP cell proliferation, whereas incubation with higher concentrations of these androgens led to a progressive decrease in cell proliferation towards basal levels. The biphasic action of androgens was also observed on apo D secretion, the effects on apo D secretion being inversely related to their action on LNCaP cell proliferation. Similar opposite biphasic effects were also observed with 9 other steroids, thus indicating that the stimulation of secretion of this new biochemical marker coincides with inhibition of cell proliferation in LNCaP human prostatic cancer cells. PMID- 1868458 TI - Accumulation of m-iodobenzylguanidine by neuroblastoma cells results from independent uptake and storage mechanisms. AB - The modalities of uptake and storage of iodine-labeled m-iodobenzylguanidine (MIBG) by four human neuroblastoma cell lines have been studied. SK-N-BE(2)C cell line has been shown to possess the specific (type 1) MIBG uptake, as well as an efficient extravesicular storage mechanism. Conversely, LAN-5 cells, which show a nonsaturation kinetic of MIBG incorporation, lack only the ability to efficiently store the MIBG taken up by a mechanism that can be pharmacologically defined as uptake 1. The two other neuroblastoma cell lines tested, GI-LI-N and GI-CA-N, lack both uptake and storage capacity. In view of the fact that the only detailed study on specific MIBG uptake by a human neuroblastoma cell line has been carried out on SK-N-SH, a highly heterogeneous cell line, our report provides new insights on the molecular and cellular pharmacology of radiolabeled MIBG. PMID- 1868459 TI - Inhibition of growth of mouse leukemic cell lines in vitro and in vivo by a monoclonal antibody that recognizes an interleukin 3 receptor-associated protein. AB - Myeloid cell lines that have achieved leukemic transformation may also have acquired the ability to produce hematopoietic growth factors. In certain instances, neutralizing antibodies directed against the growth factor have inhibited growth, supporting an autocrine mechanism in their transformation. The effect of anti-receptor antibodies on their growth and transformed phenotype has not been reported. We have developed a monoclonal antibody, 4G8, directed against a protein that is associated with the IL-3 receptor complex; 4G8 inhibits IL-3 binding and signal transduction in nonleukemic IL-3-dependent cell lines. In this study, we examined the effect of 4G8 on the growth in vitro and in vivo of leukemic cell lines, including WEHI-3B, which spontaneously produces IL-3, and NFS-60, an IL-3-dependent cell line. Our results demonstrate that the 4G8 antigen can be detected in both WEHI-3B and NFS-60 cells by flow cytometry and Western blotting; 4G8 inhibits the autonomous growth of WEHI-3B and the IL-3-dependent growth of both WEHI-3B and NFS-60. In addition, s.c. administration of 4G8 prolonged the survival of syngeneic mice given s.c. injections of WEHI-3B. These results support the conclusion that an autocrine mechanism involving IL-3 and its receptor plays a critical role in the growth and transformed phenotype of WEHI-3B and raises the possibility that anti-IL-3 receptor antibodies may be useful in the treatment of some leukemias. PMID- 1868460 TI - Frequency of urination and its effects on metabolism, pharmacokinetics, blood hemoglobin adduct formation, and liver and urinary bladder DNA adduct levels in beagle dogs given the carcinogen 4-aminobiphenyl. AB - The human urinary bladder carcinogen, 4-aminobiphenyl (ABP), is known to undergo hepatic metabolism to an N-hydroxy arylamine and its corresponding N-glucuronide. It has been proposed that these metabolites are both transported through the blood via renal filtration to the urinary bladder lumen where acidic pH can facilitate the hydrolysis of the N-glucuronide and enhance the conversion of N hydroxy-4-aminobiphenyl (N-OH-ABP) to a reactive electrophile that will form covalent adducts with urothelial DNA. Blood ABP-hemoglobin adducts, which have been used to monitor human exposure to ABP, are believed to be formed by reactions within the erythrocyte involving N-OH-ABP that has entered the circulation from the liver or from reabsorption across the urothelium. To test these hypotheses directly, experimental data were obtained from female beagles given [3H]ABP (p.o., i.v., or intraurethrally). [3H]N-OH-ABP (i.v. or intraurethrally), or [3H]N-OH-ABP N-glucuronide (i.v.). Analyses included determinations of total ABP in whole blood and plasma, ABP-hemoglobin adducts in blood erythrocytes, ABP and N-OH-ABP levels (free and N-glucuronide) in urine, urine pH, frequency of urination (controlled by urethral catheter), rates of reabsorption of ABP and N-OH-ABP across the urothelium, and apparent volumes of distribution in the blood/tissue compartment. The major ABP-DNA adduct, N-(guan-8 yl)-4-aminobiphenyl, was also measured in urothelial and liver DNA using a sensitive immunochemical method. An analog/digital hybrid computer was then utilized to construct a multicompartmental pharmacokinetic model for ABP and its metabolites that separates: (a) absorption; (b) hepatic metabolism and distribution in blood and tissues; (c) ABP-hemoglobin adduct formation; (d) hydrolysis and reabsorption in the urinary bladder lumen; and (e) excretion. Using this model, cumulative exposure of the urothelium to free N-OH-ABP was simulated from the experimental data and used to predict ABP-DNA adduct formation in the urothelium. The results indicated that exposure to N-OH-ABP and subsequent ABP-DNA adduct formation are directly dependent on voiding frequency and to a lesser extent on urine pH. This was primarily due to the finding that, after p.o. dosing of ABP to dogs, the major portion of the total N-OH-ABP entering the bladder lumen was free N-OH-ABP (0.7% of the dose), with much lower amounts as the acid-labile N-glucuronide (0.3% of the dose).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1868461 TI - Tumor subpopulation interactions affecting melphalan sensitivity in palpable mouse mammary tumors. AB - Paired mixtures of melphalan-sensitive and relatively insensitive tumor cell subpopulation lines, originally derived from the same mammary tumor, were injected s.c. into syngeneic mice. When tumors were palpable, the mice were treated with melphalan at doses shown to be effective against the melphalan sensitive subpopulations. Sensitivity was assessed by the loss of colony-forming ability of tumor cells harvested 1 to 14 days after treatment. When growing in tumors mixed with melphalan-sensitive line 4TO7 cells, line 66 (less sensitive) appeared much more sensitive than when it was grown alone. Line 66 tumors growing on the opposite sides of mice bearing line 4TO7 tumors were not more sensitive than when grown alone, indicating the lack of a systemic mechanism in the transfer of sensitivity from 4TO7 to 66. Furthermore, line 66 was not more sensitive when mixed with line 168TFAR (another melphalan-sensitive subpopulation) than when alone. The "transfer of sensitivity" from line 4TO7 to line 66 could be reproduced in collagen gel cultures but not in monolayer. Interestingly, line 4TO7, unlike line 168TFAR, is more sensitive to melphalan in collagen culture than in monolayer. This difference in sensitivity does not appear to be influenced by differences in cell density between the two culture systems. In collagen culture, the increased sensitivity of line 66 in the presence of line 4TO7 did not require cell contact and so appeared to act through diffusible factors(s). Collectively, these data suggest that the transfer of sensitivity is not dependent upon host factors or upon drug sensitivity per se but rather upon some mechanism requiring tumor cell-tumor cell interaction between specific subpopulation pairs. In additional studies, pH was ruled out as a factor in the transfer of sensitivity. PMID- 1868462 TI - Mechanism of photosensitization by microsphere-bound chlorin e6 in human bladder carcinoma cells. AB - Photodynamic therapy is an experimental method of cancer treatment in which a photosensitizer is administered and subsequently the tumor is irradiated with light. Due to problems of prolonged skin phototoxicity with hematoporphyrin derivative, new photosensitizers and methods of localization are being sought. The goal of this study was to compare the photosensitizer chlorin e6 (Ce6) free and bound to 1-micron-diameter microspheres (MS) for phototoxicity, uptake and efflux characteristics, phagocytosis rates in malignant and benign cells, and effects of NaN3, D2O, and buthionine sulfoximine on phototoxic efficacy. Incubation of MGH-U1 human bladder carcinoma cells with Ce6-MS (0.43 microM Ce6 equivalent; 18 h) and subsequent irradiation using an argon laser-pumped dye laser at a radiant exposure of 20 J/cm2 caused 100% cell death 24 h after irradiation. In contrast, MGH-U1 cells incubated with free Ce6 (0.43 microM; 18 h) remained 100% viable 24 h after irradiation at a radiant exposure of up to 50 J/cm2. The presence of D2O during irradiation increased the phototoxicity to MGH U1 cells, whereas the presence of NaN3 decreased it; these data support an important role for 1O2. Irradiation of MGH-U1 cells in the presence of the glutathione depleter buthionine sulfoximine also increased the phototoxicity, demonstrating a role for intracellular glutathione and possibly free radical intermediates. The cellular uptake of Ce6 was approximately 50 times lower than that of Ce6-MS at equivalent incubation concentrations. Efflux experiments showed that the phototoxicity of Ce6-MS was reduced by 40% for a 5-h washout time as compared to no washout time. In contrast, for free Ce6, the decrease was 95.3% under identical conditions. Because the total intracellular concentration of Ce6 MS after an efflux time of 5 h was only slightly changed, the decreased phototoxicity is attributed to an altered intracellular localization. Confocal laser scanning fluorescence microscopy data appear consistent with this hypothesis although they are not conclusive. The observed patterns were different at 0 and 5 h. Comparison of the phagocytosis rates of Ce6-MS by carcinoma and benign cells showed that on average 20 MS/cell were phagocytosed by MGH-U1 compared with 2.5 and 8.3 in the benign human fibroblasts and keratinocytes, respectively. After incubation with Ce6-MS (0.1 microM; 18 h) and irradiation at 10 J/cm2 the surviving fraction of MGH-U1 cells was 76.3 +/- 0.95% (mean +/- SE) and 40 +/- 3.49% for fibroblasts. In contrast, for keratinocytes the surviving fraction was 93.5 +/- 0.83%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1868463 TI - Hereditary renal cell carcinoma in the rat associated with nonrandom loss of chromosomes 5 and 6. AB - A spontaneous form of renal cell carcinoma occurs in rats that arises as the result of the inheritance of a mutation in a single autosomal gene. Cytogenetic analysis was performed on seven cell lines and four primary tumor cell preparations derived from this hereditary form of renal cell carcinoma. Banded karyotypes prepared from these seven lines exhibited loss and/or partial deletion of both chromosomes 5 and 6. Translocations involving chromosome 4, resulting in a net loss of genetic material located near the centromere (4q11), were observed in three of the cell lines. Monosomy, translocation, and breakage of chromosome 5 involving band 5q31 and monosomy and partial deletion of chromosome 6 involving band 6q22-q24 were independently observed in primary tumor cells from three of four tumors examined. Monosomy of chromosome 4 was observed in cells from a single tumor. The smallest region of deletion of chromosome 6 common to all the cell lines and tumor cells was 6q24, suggesting the presence of a tumor suppressor gene at this locus. These results indicate that loss of genes located on chromosomes 4, 5, and 6, possibly tumor suppressor gene(s), may be important for tumor development and/or progression in rat renal cell carcinoma and is consistent with the hypothesis that a gene locus on one of these chromosomes may be the site of the original predisposing mutation. PMID- 1868464 TI - Loss of heterozygosity of p53 gene and p53 protein expression in human colorectal carcinomas. AB - The p53 gene is a tumor suppressor gene located on chromosome 17p. Deletions of this chromosome and point mutations of p53 have been implicated in the development of colonic neoplasms. We have analyzed the loss of heterozygosity of the human p53 tumor suppressor gene in 40 cases of colorectal carcinoma using two restriction fragment length polymorphisms detected by BglII and AccII restriction enzymes. p53 gene product expression was studied immunohistochemically in 64 colorectal carcinomas, 18 adenomas, and 40 normal colonic mucosae using an anti human p53 monoclonal antibody (Pab 1801) and the avidin-biotin-peroxidase complex technique. Twelve of the 40 patients (30%) were polymorphic for the p53 gene. In ten of these informative patients (83%), the tumor samples showed the loss of one allele when compared with normal colorectal samples of the same patient. One of the homozygous patients showed a loss of both p53 alleles. p53 immunostaining was observed in 43 of 64 carcinomas (67%) but only in two adenomas (11%). These two positive adenomas showed areas of carcinoma in situ. The normal mucosa was always negative. No relation could be found between p53 immunostaining and the degree of differentiation, the extension of the tumor, or the Ki-67 proliferative index. Mucinous carcinomas and right-side carcinomas were less p53 immunoreactive (25% and 52%, respectively) than the usual adenocarcinomas (73%) and distal tumors (72%). These findings suggest that p53 may be a target of chromosome 17 deletions and that this gene may play a role in the malignant transformation of adenomas. BglII and AccII restriction fragment length polymorphism analysis of the p53 gene may be a useful and direct technique to detect allelic loss of this gene in tumors. PMID- 1868465 TI - In vivo formation of oxidized DNA bases in tumor promoter-treated mouse skin. AB - There has been a paucity of evidence showing that 12-O-tetradecanoyl-phorbol-13 acetate (TPA), a potent tumor promoter, causes DNA damage in vivo. We show that oxidized DNA bases are formed in the epidermis of TPA-treated SENCAR mice in a dose- and time-dependent manner. As measured by high-performance liquid chromatography and acetylation of nucleosides with [3H]acetic anhydride, these oxidized DNA derivatives include cis-thymidine glycol, 5-hydroxymethyl-2' deoxyuridine, and 8-hydroxyl-2'-deoxyguanosine. Their maximal formation induced by a single TPA dose occurred within 6-8 h (a 2-5-fold increase). The level of 8 hydroxyl-2'-deoxyguanosine was the lowest (3.2/10(5) bases) and remained almost unchanged for 18 h; thymidine glycol (29.1/10(4) bases) and 5-hydroxymethyl-2' deoxyuridine (17.3/10(4) bases) declined gradually but were still above controls at 24 h. Reapplication of TPA 20 h after the first dose (time of the maximal polymorphonuclear leukocyte infiltration) enhanced the net formation of 8 hydroxyl-2'-deoxyguanosine by 3.8-fold (P less than 0.05), of cis-thymidine glycol by 1.9-fold (P less than 0.001), and of 5-hydroxymethyl-2'-deoxyuridine by 2.0-fold (P less than 0.01), as compared to those maximally produced by a single TPA dose. Thus, the infiltration of polymorphonuclear leukocytes into TPA-treated mouse skin, which was corroborated by histological examination and the presence of polymorphonuclear leukocyte-specific myeloperoxidase, might play an important role in TPA-induced DNA oxidation in vivo. Our findings provide proof that tumor promoters can induce genetic modification in vivo that is oxidative in nature. Hence, formation of oxidized DNA bases may be responsible for the genetic effects of tumor promoters in carcinogenesis. PMID- 1868466 TI - Expression of the GLUT1 glucose transporter increases thymidine uptake in Chinese hamster ovary cells at low glucose concentrations. AB - An increase in expression of the GLUT1 glucose transporter gene has been observed to be associated with an increase in glucose transport activity upon oncogenic transformation of the cells. Increased expression of this glucose transporter isoform has been also observed in fetal tissues. To investigate the consequences of this phenomenon on cellular metabolism and cell growth, an expression vector containing the GLUT1 glucose transporter complementary DNA was transfected into Chinese hamster ovary cells. Overexpression of this glucose transporter isoform resulted in an increase in not only glucose uptake and utilization but also thymidine uptake when cells were exposed to glucose-deficient conditions. This increase in glucose metabolism and DNA synthesis may play an important role on the growth and/or survival of cancer cells and fetal tissues. PMID- 1868467 TI - Characterization of intestinal alkaline phosphatase expression and the tumorigenic potential of gamma-irradiated HeLa x fibroblast cell hybrids. AB - Fusion of tumorigenic HeLa cells with human skin fibroblasts results in genetically stable hybrids which are nontumorigenic and no longer express the HeLa tumor-associated antigen, intestinal alkaline phosphatase (IAP). Previous analysis of spontaneous segregants of the nontumorigenic hybrid have implicated the loss of one copy of human fibroblast chromosome 11 with reexpression of IAP and tumorigenicity. This observation suggests that a putative HeLa tumor suppressor gene(s) is located on chromosome 11 and that this gene may be a negative regulator of the IAP gene. We have isolated several gamma-ray-induced mutants (GIMs) of the nontumorigenic HeLa x skin fibroblast hybrid CGL1 that were specifically selected for reexpression of IAP to further investigate the potential linkage between IAP regulation and the putative tumor suppressor locus. The GIMs have a wide range of cell morphology and level of IAP expression (nearly a factor of 40). The tumorigenicity of the GIMs was examined by s.c. injection into nude mice and all were found to be tumorigenic. The tumor volume-doubling time is in the range of 4 to 8 days for all the cell lines; however, the lag time to reach 500 mm3 tumor volume was significantly longer when the GIM IAP activity was low (less than 20% relative activity), suggesting perhaps that there is a threshold level of IAP expression required for tumor formation and selection for high IAP expression in vivo. However, studies with tumor reconstitutes of the GIMs and transfection studies with an IAP complementary DNA expression vector indicate that high IAP expression alone is not sufficient to confer rapid tumor growth. Therefore, while the data lend strong support to the continued tight correlation between IAP reexpression and tumorigenicity and to our proposal that the tumor suppressor may negatively regulate the IAP gene, it suggests that selection for other gene activities may be responsible for aggressive tumor growth in this cell hybrid system. PMID- 1868468 TI - Progestin regulation of alkaline phosphatase in the human breast cancer cell line T47D. AB - In T47D breast cancer cell line, progestin (R5020) induces de novo synthesis of an alkaline phosphatase enzyme. Based on inhibitor profiles and antigenic specificity, it is apparent that this enzyme belongs to the class of membrane associated tissue-unspecific alkaline phosphatases. Enzyme induction was uniquely specific to progestins and not altered by other steroid hormones or synthetic analogues. The progestin induction of the tissue-unspecific alkaline phosphatase was time and dose dependent. The protein synthesis inhibitor cycloheximide blocks the enzyme synthesis and tunicamycin blocks the enzyme activity, showing that the induction was new synthesis of protein in its complete glycosylated form and not activation of a preexisting enzyme. To our knowledge this is the first report of progesterone-induced expression of a tissue-unspecific alkaline phosphatase gene of such magnitude (about 30- to 100-fold) in a progesterone-responsive tissue. PMID- 1868469 TI - Tumor necrosis factor expression by human ovarian carcinoma in vivo. AB - Tumor necrosis factor (TNF) is a cytokine produced by monocytes and other cells with selective cytolytic activity against some but not all tumor cells. Cellular resistance to the cytolytic effects of TNF has been reported to be associated with autocrine production of TNF by the target cells. The purpose of this study was to determine whether or not human tumors produce tumor necrosis factor in vivo. Ovarian carcinoma tissue from 25 patients with ovarian carcinoma was examined for the presence of TNF. Four of 5 ascites fluid specimens and tissue sections of 16 of 20 patients were positive for TNF by immunoperoxidase staining. The source of the immunoreactive protein was further examined by in situ hybridization studies. TNF mRNA was detectable in each of the ascites specimens and 7 of 16 tissue sections that were positive by immunoperoxidase staining. These findings suggest that TNF is produced by some human tumors in vivo and that the association between TNF production and resistance to TNF antitumor action may be clinically relevant. PMID- 1868470 TI - Intraocular tumor formation of RB reconstituted retinoblastoma cells. AB - It has been reported that replacement of a functional retinoblastoma (RB) gene in RB defective WERI-27 retinoblastoma cells results in complete loss of their tumorigenic potential in nude mice following s.c. injection. We have repeated the identical studies and found that although tumors did not develop s.c., the RB reconstituted cells, either soon after RB virus infection or after long term cultivation, consistently produced tumors when injected intraocularly. These tumor cells, when reestablished in culture, were found to retain a normal RB protein as determined by direct Western blotting and immunocytochemical staining. The tumors, however, occurred with a longer average latency period and with less frequency compared to those produced by the parental RB defective cells. Our results suggest that reintroduction of the RB gene into WERI-27 cells reduces but does not completely suppress their tumorigenic potential. Since retinoblastoma is an eye tumor it also provides further documentation that the use of an orthotopic injection site can be critical when determining the tumorigenicity of a given cell type. PMID- 1868471 TI - Ha-ras induction of the invasive phenotype results in up-regulation of epidermal growth factor receptors and altered responsiveness to epidermal growth factor in human papillary transitional cell carcinoma cells. AB - Recent studies have shown that orthotopic (transurethral) transplantation of human bladder cancer cell lines into nude mice permits tumor growth that more accurately reflects their clinical malignant status in the original host. We have previously demonstrated that transfection and overexpression of normal or mutated c-Ha-ras genes into a noninvasive human papillary transitional cell carcinoma cell line confer upon these cells an invasive phenotype in vivo with behavior remarkably similar to the clinical behavior of high grade bladder carcinomas. Since elevated expression levels of the epidermal growth factor receptor (EGF-R), in addition to that of c-Ha-ras, have been correlated with transitional cell carcinoma progression, we sought to determine whether up-regulation of the EGF-R had occurred in the invasive high ras expressors and if so, what functional significance this might have. Our results show that invasive cell lines which overexpress the c-Ha-ras gene also have increased epidermal EGF-R expression. This was found to occur at both the protein and mRNA levels, and analysis of the EGF-R promoter/enhancer sequences has revealed a putative AP-1 site which may possibly enhancer sequences has revealed a putative AP-1 site which may possibly serve as a ras response element. In addition, we found that the cells overexpressing the EGF-R had acquired a positive sensitivity to the stimulatory mitogenic effects of EGF. Hence, the results obtained suggest a role for either a normal or a mutated overexpressing Ha-ras in up-regulating the surface EGF-R, possibly through an AP-1 site during human bladder carcinoma progression; they also highlight the potential that EGF may have in cooperating with this EGF-R up regulation to help mediate enhanced tumor growth. PMID- 1868472 TI - Altered intracellular calcium regulation in human colorectal cancers and in "normal" adjacent mucosa. AB - Intracellular calcium [(Ca2+)i] was measured in human colonic epithelia derived from control mucosa from noncancer patients, from grossly "normal" mucosa taken 10-30 cm proximal to primary colorectal cancers, and from colorectal cancers. (Ca2+)i was measured first in cells bathed by calcium-free solution and again after adding 1 mM calcium. Compared to control mucosa, (Ca2+)i was 27% lower in cancer cells in the presence of 1 mM extracellular calcium, whereas (Ca2+)i was elevated more than 3-fold in the adjacent "normal" mucosa from cancer patients in both media. These results suggest altered (Ca2+)i levels in malignant cells and the presence of a "field defect" in (Ca2+)i regulation in "normal" colonic mucosa adjacent to colorectal cancers. PMID- 1868473 TI - p53 gene mutations in Barrett's epithelium and esophageal cancer. AB - Genomic DNA was extracted from archival pathology specimens comprising 10 squamous and 14 adenocarcinomas, including 7 with Barrett's epithelium adjacent to tumor, and corresponding normal esophagus from the resection margin. The polymerase chain reaction was used to amplify selected exons of p53 which were analyzed for mutations using single-strand conformation polymorphism analysis. Mutations were localized to exon 8 for 1 adenocarcinoma and to exon 5 for 1 squamous tumor and 4 of 7 Barrett's specimens. Sequencing confirmed mutations at codons 273 (CGT----CAT; adenocarcinoma) and 176 (TGC----TTC; squamous) and in Barrett's epithelium at codons 152 (CCG----CTG), 155 (ACC----GCC) and 175 (CGC--- CAC). Specimens of Barrett's epithelium from separate sites had identical p53 mutations suggesting a clonal origin. Cancers arising in mutant epithelium did not have mutations corresponding to those found in the Barrett's specimens suggesting that other events are required for tumorigenesis. PMID- 1868474 TI - Dietary-induced hyperlipidemia and renal function in the uremic rat. AB - Rats made uremic by 2-stage 5/6 nephrectomy and sham-operated control animals were fed either a normal laboratory chow, a high-sucrose (60%) or a high-fat (10% cholesterol; 20% olive oil) diet, all containing 21% protein and identical amounts of electrolytes, vitamins and trace elements. Serum creatinine levels remained unchanged in the control animals but rose in the 5/6 nephrectomised uremic animals by a factor of 2.7 from a mean of 0.44 +/- 0.05 mg/dl to 1.20 +/- 0.11 mg/dl at 8 weeks, without differences between the dietary groups. During 8 weeks of dietary regimen the high-sucrose and high-fat diets induced significant hypertriglyceridemia, generally similar in control and uremic rats. The uremic animals on a high-sucrose and high-fat diet had the most pronounced rise in serum triglycerides, 331.5 +/- 89.0 and 298.0 +/- 45.0 mg/dl, respectively (control: 159.9 +/- 14.0 mg/dl). After 4 and 8 weeks, only the animals on the high-fat diet had significant hypercholesterolemia, most pronounced in the uremic animals (356 +/- 56.3 mg/dl; control: 71.6 +/- 12.9 mg/dl). The animals in the latter group also had significant proteinuria and renal histologic abnormalities consisting of xanthoma-like glomerular lesions, infiltrates and fibrosis not seen in the other groups of animals. These data indicate that dietary-induced hyperlipidemia of short duration causes or aggravates renal damage in the rat with mild-moderate uremia, induced by ablation. PMID- 1868475 TI - Use of the captopril test to assess renin responsiveness in children with hypertension and renal disease. AB - The captopril test was performed on 49 children of whom 36 were hypertensive, and the remainder were normotensive but were at risk for developing hypertension because of scarred kidneys secondary to vesico-ureteral reflux. Blood pressure (BP) was monitored in fasting supine patients throughout the duration of the test. Blood was taken for measurement of plasma renin activity (PRA); then captopril (0.7 mg/kg of body weight) was administered orally. A second blood sample was taken for PRA at 90 min postcaptopril. The mean (SEM) PRA at 90 min was 11.90 (4.01) ng/l/s [42.84 (14.44) ng/ml/h] in 7 patients with renovascular disease. In 4 patients with essential hypertension corresponding values were 0.88 (0.38) ng/l/s [3.17 (1.37) ng/ml/h]. Patients with other renal diseases showed variable values. Some individuals had PRA values as high as those of patients with renovascular disease, but the etiology of their hypertension was usually clinically evident. Our preliminary data would suggest that the captopril test may help differentiate between patients with essential hypertension and those with renovascular disease, or may help select patients that should be followed up by more definitive diagnostic procedures. PMID- 1868476 TI - The prognostic significance of acute neonatal renal failure. AB - We evaluated 38 newborns with acute renal failure (plasma creatinine (Pcr) concentration greater than = 1.5 mg/dl), measured between the 2nd and 5th days. We used renal ultrasound to exclude the possibility of congenital renal anomalies, obstructive pathology or vascular disorders. We calculated the glomerular filtration rate (GFR) using Schwartz' formula and the maximal concentrating capacity using intranasal administration of desamino-cis-1-D arginine-8-vasopressin (DDAVP test). Two newborns were treated with peritoneal dialysis and died during the first month of life. Thirty-six had a follow-up blood sample drawn: 24 preterm babies between 1 and 12 months, and 12 full-term babies between 1 and 36 months of life. From this sampling 4 babies (11.1%) showed defective maximal concentrating ability. Our data reveal the persistence of altered concentrating ability in newborns affected by renal failure and shows that this problem needs a longitudinal study and further diagnostic investigations. PMID- 1868477 TI - Acquired cystic kidney disease in renal insufficiency. AB - The frequency of acquired cystic kidney disease (ACKD) in adult patients with end stage renal failure (ESRF) varies from 8 to 95%. Systematic data are available neither on children with chronic renal insufficiency (CRI) nor on the frequency of ACKD in children below 15 years undergoing dialysis. Twenty-one children with CRI and 28 patients with ESRF were investigated. The age of the children ranged from 1 month to 15.8 years. Ultrasonographic examination determined the incidence of ACKD; in some children computerized tomography was performed. ACKD was diagnosed in 2 children (9.8%) with CRI and in 6 (21.6%) with ESRF. Diagnostic criteria and evolution of ACKD within the observation period of 3-48 months (mean 23.4 +/- 12.6 months) are discussed. PMID- 1868478 TI - Postrenal-biopsy hematoma in infants and children: evaluation by ultrasonography. AB - Postbiopsy hematoma was assessed using ultrasonography in 106 infants and children (age 1 month to 15 years) who underwent a total of 122 percutaneous renal biopsies. Postbiopsy hematoma occurred in 22 (21%) of 105 successful biopsies. However, only 2 of these were symptomatic. Renal failure, mild and moderate hypertension and inexperience of the operator were not found to increase the incidence of postbiopsy hematoma in infants and children. PMID- 1868479 TI - Treatment of vesicoureteric reflux: results after 3 years in a prospective study. AB - Between 1982 and 1986, 96 children with nonobstructive vesicoureteric reflux were treated in a prospective study. There were 134 refluxing ureters. Results are reported after a follow-up period of 3 years in 94 children with 130 refluxing ureters. Initially all children with reflux grade III or less had antibiotic treatment only. Those with reflux grade IV were randomized for antibiotic treatment alone versus surgery plus antibiotic treatment, while the primary treatment of reflux grade V was reimplantation. In 84 ureters treated by antibiotics alone, reflux disappeared in 52 cases and in 18 ureters the reflux was reduced. In 49 ureters treated by reimplantation, reflux was cured in 39 cases and no severe ureteric obstruction was seen. Conservative management of reflux grade IV was less successful than surgery. The results of conservative, nonsurgical treatment of reflux grade I to III are satisfactory, but for grades IV and V reflux surgery should be the treatment of choice, provided that detrusor instability can be excluded. PMID- 1868480 TI - Age-related changes in renal reserve and renal tubular function in healthy humans. AB - To explore the age-related changes in tubular function and in the renal reserve (RR) a total of 98 healthy subjects were studied while on free living conditions. Enrolled people were divided into 3 groups: group A (n = 40, age range 5-18 years, Na intake 80 +/- 20 mM/day, protein intake 1.30 +/- 0.76 g/kg BW); group B (n = 34, age range 19-60 years, Na intake 110 +/- 12 mM/day, protein intake 1.32 +/- 0.75 g/kg BW), and group C (n = 24, age range 61-89 years, Na intake 159 +/- 12 mM/day (p less than 0.01 vs. A and B), protein intake 1.26 +/- 0.23). Glomerular filtration rate (GFR) (inulin), renal plasma flow (p-aminohippurate), the amount of filtrate and sodium delivered from the proximal tubule (lithium clearance), endogenous creatinine clearance, and predicted creatinine clearance were measured. The RR was evaluated after a meat meal (providing 2 g/kg BW of proteins) by subtracting baseline GFR from the peaking postprandial GFR. GFR was age-related and was identical in groups A and B and significantly lower in group C (p less than 0.0001). The drop in GFR averaged 7% per decade in the age range 61-89 years. The RR was not statistically different in groups A and B and increased significantly in group C (p less than 0.0001). In groups A and B the filtration fraction was constant after the meat meal and significantly increased over baseline GFR in group C (p less than 0.01), while the percentage of filtration capacity utilized at rest was lower in group C (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868481 TI - Seizures and transient blindness following intravenous pulse methylprednisolone in children with primary glomerulonephritis. AB - Two children, 1 with idiopathic nephrotic syndrome and 1 with endo-extracapillary glomerulonephritis, presented an episode of seizures and transient blindness at different times after i.v. pulse methylprednisolone (IVPMP) treatment. Neurological manifestations in patient 1 could be due to hypertension secondary to IVPMP, while the pathogenesis of such manifestations remained difficult to clarify in patient 2. The severity of uremia in patient 2 could be one of the conditions that, in association with the abrupt changes obtained with IVPMP, predispose to neurological manifestations. Careful clinical and biochemical monitoring seems necessary in children with primary glomerulonephritis, other than those transplanted, after IVPMP, and factors predisposing to neurologic sequelae should be further defined. PMID- 1868482 TI - Bladder transitional cell carcinoma. AB - We present a case of urinary bladder carcinoma in a child aged 13 that followed a benign course. This confirms the idea that epithelial bladder cancer in children pursues, a much less aggressive behaviour than in the adult, possibly on the basis of its well-differentiated nature. Despite the rarity of the lesion, it should not be overlooked in the differential diagnosis of haematuria in children. PMID- 1868483 TI - Pitfalls in the treatment of congenital urologic anomalies. AB - Specific diagnostic and therapeutic considerations regarding urologic problems in the very young have encouraged the awareness that the treatment of congenital malformations requires special qualifications. In this paper 3 cases are presented to illustrate and stress our opinion that the treatment of congenital urologic anomalies in young children should be left to urologists who have been trained and work in the field of paediatric urology. PMID- 1868484 TI - Familial nephrotic syndrome and HLA-DR5. AB - Two different types of familial nephrotic syndrome were observed in two unrelated families. In the first family, 2 siblings, both boys without hearing impairment, had proteinuria which was evident after 10 years of age and were resistant to steroid and immunosuppressant therapy. Their renal biopsy findings were compatible with focal-segmental glomerulosclerosis. In the second family, an elder sister and a boy had minimal-change nephrotic syndrome which responded well to steroid and immunosuppressant therapy. All 4 patients had HLA-DR5 in common, suggesting that this gene locus may play an important role in the pathogenesis of familial nephrotic syndrome. PMID- 1868485 TI - Relations between hypertension and glomerulosclerosis in first-generation hybrid rats of the Milan strains. AB - In the Milan hypertensive rats (MHS) glomerulosclerosis is less evident than in the normotensive strain (MNS). To clarify whether this pattern is due to a 'protective effect' of increased afferent arteriolar tone or to a different mechanism, we studied 12 first-generation hybrids (F1), 4 parental MHS and 4 parental MNS rats. Four-micrometer sections were stained with hematoxylin, Mallory's trichrome stain and periodic acid-Schiff reaction. The blood pressure of the F1 rats was only slightly higher than that of the MNS so that very probably renal vascular resistances were similar. The F1 rats had low proteinuria (23.3 +/- 2.7 mg/24 h) like the MHS (25.3 +/- 4.8), and few damaged glomeruli per section (18.5 +/- 1.2), again like the MHS (18.7 +/- 1.1). MNS had higher proteinuria (363.8 +/- 111.6; p less than 0.01 vs. MHS and F1) with a greater number of damaged glomeruli (51.4 +/- 4.5; p less than 0.01 vs. MHS and F1). The difference in afferent arteriolar resistance is not implicated in glomerulosclerosis. PMID- 1868486 TI - Comparative efficacy of liposomes containing synthetic bacterial cell wall analogues for tumoricidal activation of monocytes and macrophages. AB - We examined the activation to the tumoricidal state of normal mouse peritoneal exudate macrophages, bone marrow macrophages, and human blood monocytes by liposomes containing either lipophilic muramyl tripeptide (CGP 19,835) or a new synthetic analogue of lipoprotein from gram-negative bacteria outer wall, CGP 31,362, or combinations of the two. The superiority of liposomes containing the synthetic lipopeptide over liposomes containing lipophilic muramyl tripeptide for in vitro activation of monocytes and macrophages was demonstrated in several experiments. First, liposome-CGP-19,835 activated monocytes only in the presence of interferon-gamma, whereas activation with liposome-CGP 31,362 was interferon independent. Second, activation of both mouse macrophages and human blood monocytes by liposome-CGP 31,362 occurred at a lower liposomal concentration than that by liposome-CGP 19,835. Third, monocytes incubated with liposome-CGP 31,362 released both tumor necrosis factor (TNF) and interleukin-1 activities, whereas monocytes treated with liposome-CGP 19,835 (in the absence of interferon-gamma) released only TNF activity. These data suggest that liposomes containing the synthetic lipopeptide CGP 31,362 are superior to liposomes containing CGP 19,835 for systemic activation of macrophages. PMID- 1868487 TI - Dietary restriction reduces the incidence of 3-methylcholanthrene-induced tumors in mice: close correlation with its potentiating effect on host T cell functions. AB - All mice treated with 3-methylcholanthrene (MC) suffered with tumor 114 days after treatment. However, 40% dietary restriction caused a great inhibition of tumor incidence. In order to understand the mechanisms by which dietary restriction decreased the occurrence of tumor in mice, we investigated the correlation between tumor incidence and host T cell immune responses. At 114 days after MC administration, the mice were sacrificed and their T cell immune responses were assessed. Flow cytometry studies demonstrated that dietary restriction caused a marked increase of the proportion of Thy 1.2+, L3T4+ T cells in MC-treated diet-restricted mice. Consistent with this result, T cell responses against concanavalin A and interleukin-2 were also potentiated in spleen cells obtained from MC-treated diet-restricted mice, while spleen cells obtained from MC-treated unrestricted mice showed decreased T cell responses because of their tumor burden. Such potentiation of T cell functions by dietary restriction was also observed at earlier stages of MC-induced tumorigenesis. During the course of carcinogenesis, spleen cells obtained from diet-restricted mice showed decreased natural killer activity in vivo. However, in vitro induction of cytotoxic T cells was markedly augmented in MC-treated diet-restricted mice compared with unrestricted mice. These results strongly suggest that the increase of host T cell immune responses might be one of the major causes for the reduction of tumor occurrence by dietary restriction. PMID- 1868488 TI - In situ activation of syngeneic tumour-specific cytotoxic T lymphocytes: intra pinna immunization followed by restimulation in the peritoneal cavity. AB - Tumour-specific cytotoxic T lymphocytes (CTL) are usually obtained after immunization in vivo and restimulation of immune cells in vitro. We here describe the generation of syngeneic tumour-specific CTL within no more than 9 days by priming and restimulation in vivo. This is achieved only if the correct sites are used both for primary immunization (ear pinna) and for restimulation (peritoneal cavity). The kinetics of immune T cell induction and of the secondary response in vivo will be reported. While a secondary CTL response could be generated in the peritoneal cavity, this was not possible in the spleen, no matter which routes of antigen restimulation were used. Upon transfer of immune spleen cells into the peritoneal cavity but not into the spleen, a secondary response could be generated upon in situ restimulation, indicating the importance of the correct microenvironment for this type of response. The peritoneal effector cells were true T cells and recognized a tumour-associated antigen in association with the Kd major histocompatibility (MHC class I) antigen. Finally the activated tumour specific peritoneal exudate cells were able to transfer protective immunity without exogenous interleukin-2 into normal syngeneic mice. PMID- 1868489 TI - Inhibition of spontaneous pulmonary metastases of Lewis lung carcinoma by oral treatment with Respivax and Broncho-Vaxom. AB - The antimetastatic activity of orally administered polybacterial vaccines, Broncho-Vaxom (BV) and Respivax (RV) was examined in C57BL/6 mice, bearing implants of Lewis lung carcinoma (3LL) in the footpad. The oral administration of BV or RV for 10 consecutive days before or after surgery caused significant reduction of the number and volume of lung metastases. In addition, the therapeutic potential of BV and RV was examined in combination with chemotherapy to determine if there is additive activity. In animals bearing pulmonary micrometastases, treatment with a combination of cyclophosphamide at 50-150 mg/kg with BV or RV was found to be more effective than each of these treatments alone. In immune function studies it was established that the oral administration of BV and RV induced an increase in the number of cells, recovered by broncho-alveolar lavage, and alveolar macrophages were dominant in these cell populations. Furthermore, oral treatment of mice with these vaccines rendered their alveolar macrophages tumoricidal for syngeneic metastatic 3LL cells in vitro. These results show that pulmonary macrophages induced by oral administration of BV and RV played a key role in the inhibition of metastasis in 3LL-bearing mice. PMID- 1868490 TI - Monocyte tumoricidal activity and tumor necrosis factor production in patients with malignant brain tumors. AB - Monocyte-mediated tumoricidal activity, tumor necrosis factor alpha (TNF alpha) secretion and gene expression were examined in astrocytoma patients, patients with other types of brain tumors (primary or metastatic), and normal individuals. The spontaneous monocyte-mediated tumoricidal activity of either patient group against an astrocytoma cell line was significantly greater than normal. There was no difference between patient groups. When monocytes were stimulated with lipopolysaccharide in vitro, tumoricidal activity increased in all patient groups. Patient monocyte activity tested shortly (48 h) after surgery was not different from that before surgery. Both spontaneous and stimulated monocyte cytocidal activities were tumor-cell-restricted: melanoma and astrocytoma cells were equally susceptible but non-neoplastic glial cells were not affected. Examination of monocyte TNF alpha secretion and mRNA expression indicated that patient activity was comparable to or greater than normal. These results demonstrate that, despite steroid therapy, circulating monocytes in astrocytoma and other brain tumor patients retain intact functional activity. PMID- 1868492 TI - Localization of human sarcoma with radiolabeled monoclonal antibody--a follow-up report. AB - A group of 16 sarcoma patients with suspected advanced disease were studied with a radiolabeled anti-sarcoma monoclonal antibody (mAb 19-24) in an attempt to localize tumor deposits. All 16 patients received 125I-mAb 19-24 and then had external-probe analysis and imaging performed. Confirmation of tumor deposits was done at surgery or by autopsy. Tissues were studied in surgical patients when possible and analyzed for radioactivity, and tumor-to-blood ratios ranged from 0.6 to 36.8. In conjunction with the patients previously studied, probe results had an overall sensitivity of 83.3% and an overall specificity of 100%; scintigraphic results showed an overall sensitivity of 78.9% and an overall specificity of 100%. Radiolabeled mAb 19-24 may be developed into a useful tool for clinical immunodetection of sarcoma deposits. PMID- 1868491 TI - Immunopathological features of human pulmonary tumors following low-dose interleukin-2. AB - We administered preoperative low-dose interleukin-2 (IL-2) to 10 patients undergoing thoracotomy for pulmonary tumors. The in vivo effect of IL-2 on tumor associated lymphocyte activity was assessed in the resected specimens by immunohistochemistry and compared with observations in 45 patients who did not receive IL-2. H & E evaluation revealed an increase in intra- and peritumoral lymphocyte infiltration in the IL-2-treated patients. Immunopathological evaluation with monoclonal antibodies revealed that this lymphocyte infiltration was predominantly CD5-positive T cells. The amount of intra- and peritumoral lymphocyte activity correlated with the dose of IL-2 administered (6000-90,000 international units/kg every 8 h for 48 h. IL-2-treated patients showed increases in T-cell-associated activation markers (IL-2 alpha-receptor, transferrin receptor and HLA-DR) on peritumoral lymphocytes, but not on intratumoral lymphocytes. We previously reported that low-dose IL-2 increases the intrinsic natural killer cell cytotoxicity of intratumoral lymphocytes and suggest that this lymphocyte infiltration is further evidence that low-dose IL-2 can augment in vivo lymphocyte activity at the tumor site. PMID- 1868494 TI - Increased level of HLA-DR-expressing T lymphocytes in peripheral blood from patients with idiopathic dilated cardiomyopathy. AB - Peripheral blood leukocytes from 14 patients with idiopathic dilated cardiomyopathy (IDC), 13 patients with ischemic congestive heart failure, and 12 controls were characterized using different antibodies. The proportions of B lymphocytes, T lymphocytes, and the different T lymphocyte subsets were estimated. No difference between the three groups could be found in the various T and B cells subpopulations. Using a two-color direct immunofluorescence technique, the occurrence of circulating T helper/inducer (Leu-3a) and T cytotoxic/suppressor cells (Leu-2a) expressing HLA-DR antigens was examined. Only IDC patients demonstrated increased levels of HLA-DR-positive T helper/inducer cells (2.8 +/- 2.4%) and T cytotoxic/suppressor cells (2.8 +/- 2.3%) as compared with patients with ischemic congestive heart failure (0.8 +/- 0.7 and 1.0 +/- 1.0%, respectively) and controls (0.6 +/- 0.5 and 0.9 +/- 0.6%, respectively). When individual IDC patients were studied, 4 out of 12 patients had an increased level of HLA-DR-expressing T helper/inducer cells, and 7 out of 12 patients had elevated HLA-DR-positive T cytotoxic/suppressor cells. The findings suggest that activation of the T lymphocytes may be of importance in the pathogenesis of IDC. PMID- 1868493 TI - Treatment of chemically induced autochthonous rat mammary and colorectal carcinomas with interleukin-2. AB - The antineoplastic efficacy of human interleukin-2 (IL-2) in autochthonous methylnitrosourea-induced mammary carcinoma and in acetoxymethyl-methyl nitrosamine-induced colorectal carcinoma of Sprague Dawley rats has been investigated. Under the conditions applied, IL-2 was non-toxic. In the mammary carcinoma IL-2 was therapeutically inactive. In the colorectal carcinoma, 1200 U IL-2/day exhibited significant antitumour activity in established tumours as well as in tumours treated "prophylactically" before their manifestation (P less than 0.05). The effect of IL-2 seemed to be more pronounced when given before manifestation of colorectal tumours (T/C = 8.7% vs 17.8% in established tumours). The differential sensitivity of the autochthonous mammary and colorectal carcinoma may be explained by differences in their proliferation rates and differences in volumes at the beginning of IL-2 therapy. IL-2 seems to be preferentially active in small tumours with a low proliferation rate, a feature typical of colon tumours. PMID- 1868495 TI - Spontaneous late recanalization of occluded saphenous vein coronary artery grafts. PMID- 1868496 TI - Hemodynamic changes during retrograde left-heart catheterization in patients with aortic stenosis. AB - Pulmonary artery pressures in patients with aortic stenosis have been related to postoperative prognosis and surgical risk. However, while right- and left-heart pressures should be measured simultaneously, a catheter lying across the stenotic aortic valve might alter left- and right-heart pressures. To assess this phenomenon, right- and left-heart pressures were recorded before and after retrograde crossing of the aortic valve in 51 patients (30 patients with and 21 without aortic stenosis). In aortic stenosis, the mean pulmonary artery pressure increased (p less than 0.001) after transaortic valvular pressure catheter placement (average 4 mm Hg, peak 19 mm Hg); in the absence of aortic stenosis, the mean pulmonary artery pressure did not change (average 0 mm Hg; NS). A similar response was noted for the mean pulmonary capillary wedge pressure. Hemodynamic changes did not correlate with the severity of aortic stenosis or with left ventricular performance. Right-heart pressures should be determined without transaortic valvular catheter in place, if accurate interpretation of the hemodynamic effects of aortic stenosis is to be achieved. PMID- 1868497 TI - Triglyceride and glucose intolerance as a risk factor for coronary heart disease. AB - The electrophoresis of plasma lipoproteins frequently showed midbands between beta- and pre-beta-lipoproteins in survivors of myocardial infarction. There were increases in intermediate-density-lipoprotein (IDL) cholesterol and triglycerides with an increase in IDL cholesterol/triglycerides in the very-low-density lipoprotein fraction, even if the increase in cholesterol was not so significant. Impaired glucose tolerance (IGT) was also frequently found in these patients. Among the patients with an apparently normal glucose tolerance, the coronary atherosclerosis scores judged by the American Heart Association reporting system on coronary angiography increased as the total insulin area by 75 g oral glucose tolerance test increased. The correlation between the atherosclerosis score and the insulin area was still significant even after adjustment for body mass index and plasma triglyceride level. Our data suggest that hypertriglyceridemia, IGT, and hyperinsulinemia may become independent risk factors for atherosclerosis in addition to cholesterol. Another study showed that the morbidity of coronary heart disease increased with an elevation of plasma triglyceride levels among patients with familial hypercholesterolemia. PMID- 1868498 TI - Hyperlipoproteinemia in chronic renal failure: pathophysiological and therapeutic aspects. AB - Dyslipidemia of chronic renal failure is of multifactorial origin. Decreased activity of lipoprotein lipase and hepatic triglyceride lipase, peripheral insulin resistance, hyperparathyroidism and L-carnitine deficiency are the contributing factors. This results in a disturbed catabolism of chylomicron, accumulation of very-low-density (VLDL) and intermediate-density (IDL) lipoproteins as well as incompletely cleared remnant particles, whereas low density lipoprotein (LDL) levels are diminished. There is current debate as to whether cardiovascular disease is accelerated and whether hyperlipidemia should specifically be treated. In addition, there have been few means of influencing these metabolic alterations. Drug incompatibility and consequently side effects render treatment difficult. The drugs that have been most tested for lipid lowering in chronic renal failure are the fibric acids. By their mode of action, they are the logical choice. Dose reduction overcomes major side effects such as myopathy and rhabdomyolysis. The second generation of fibric acid derivatives (gemfibrozil and beclobrate) show several advantages over formerly used derivatives. Treatment with lovastatin and simvastatin appears to be safe and is recommended in a minority of patients with predominantly elevations of LDL. HMG CoA reductase inhibitors also lower remnant particles effectively in hemodialysis (HD) patients. L-Carnitine and low-molecular-weight heparin have been shown to influence VLDL rich in triglycerides in a subset of patients on HD. In posttransplant hyperlipidemia, diet remains the first course of action in all patients. When this approach fails, the new lipid-lowering agents, especially fibric acids, appear to be safe in short-term studies in azathioprine- and ciclosporin-treated patients. Lovastatin has been shown to be safe in stable renal transplant patients. Its toxicity seems to depend mainly on high ciclosporin whole blood through or plasma levels. PMID- 1868499 TI - Drugs affecting triglycerides. AB - Nicotinic acid and clofibrate derivatives are the main triglyceride-metabolism affecting drugs. Nicotinic acid and its derivatives block adipose tissue lipolysis thus reducing the FFA flux of free fatty acids to the liver and the synthesis of very-low-density lipoproteins (VLDL). VLDL removal rate is also enhanced. Disturbing side effects (mostly flushing) limit the use of this compound. Clofibrate and its derivatives decrease the synthesis of VLDL and increase their catabolism. Lipoprotein lipase activity as well as VLDL fractional catabolic rate are increased by fibrates. Triglyceride synthesis is also reduced. PMID- 1868500 TI - Mechanisms of lipid-lowering agents. AB - Lipid-lowering agents are used with the purpose of ameliorating hyperlipoproteinemias, in order to prevent arterial disease. Lipid-lowering drugs can be classified into absorbable agents and into nonabsorbable compounds, acting within the gastrointestinal lumen. Absorbable drugs (fibric acids, nicotinic acid, probucol, HMG-CoA reductase inhibitors) reduce plasma very-low-density lipoproteins (VLDL) and/or low-density lipoproteins (LDL) by a variety of mechanisms. Fibric acids, in particular, act by stimulating the catabolism of VLDL and also, as a consequence, improving LDL delipidation, thus favoring receptor uptake. Nicotinic acid and acipimox interfere with the biosynthesis of LDL and can also improve the clearance of VLDL/LDL. Probucol acts by a newly described mechanism, i.e. accelerating reverse transport of cholesteryl esters from high-density lipoproteins to lower-density lipoproteins. Finally, HMG-CoA reductase inhibitors, interfering with the biosynthesis of cholesterol, can induce an increased expression of liver high-affinity lipoprotein receptors. Nonabsorbable agents (anion-exchange resins, neomycin, beta-sitosterol) interrupt the recirculation of bile acids and/or reduce the absorption of cholesterol with the gut. They display a selective activity on hypercholesterolemia, again by increasing LDL receptor expression. The choice of one or more lipid-lowering agents will depend upon the patient's phenotype, determining responsiveness to the pharmacological treatment. PMID- 1868501 TI - Drugs affecting HDL cholesterol. PMID- 1868502 TI - Comparative effects of long-term therapy with captopril and ibopamine in chronic congestive heart failure in old patients. AB - Little is known concerning the long-term drug management of chronic heart failure (CHF) in old patients (greater than or equal to 75 years). Accordingly, this double-blind, placebo-controlled trial compared the long-term (over 6 months) effect of captopril (37.5-75 mg/day) and of ibopamine (150-300 mg/day) on exercise testing, symptoms and subjective feeling of well-being, in 150 CHF elderly patients (mean age 75 years) under treatment with digitalis and/or diuretics. During an additional open follow-up of approximately 1.5 years, morbid events and deaths were also recorded. Captopril and ibopamine performed better (p less than 0.01) than placebo, improving the 6-min walking distance (captopril from 300 to 404 m, ibopamine from 282 to 385 m; placebo from 283 to 299 m). NYHA status, symptom score and patients' global assessment. The difference between the active study drugs was not statistically significant (p greater than 0.05). Complicating events, including diuretic use, frequency of hospitalization, worsening of CHF and deaths, were grouped by patient-years. These events were significantly (p less than 0.01) lower (captopril: 28/75 patient-years; ibopamine 33/74 patient-years) in the active treatment groups with respect to placebo (58/96 patient-years). Captopril and ibopamine showed a different safety profile. Creatinine increase (2 patients), symptomatic hypotension (4 patients), hyperkalemia (2 patients) and upper respiratory symptoms were mostly associated with captopril treatment. Gastrointestinal adverse events were observed in 11 patients under ibopamine treatment. The study provides evidence of the clinical usefulness of both captopril or ibopamine in the long-term treatment of CHF in old patients. The safety profile of each drug will suggest the preferred therapeutic application. PMID- 1868503 TI - Seminars in thrombosis, thrombolysis, and vascular biology. Part 2: Coagulation and thrombosis. AB - The hemostatic mechanism is a critical component of a normally functioning circulatory system, preventing life-threatening hemorrhage and assisting in the maintenance of vascular integrity. For longer than half a century, however, nonphysiological intravascular coagulation and thrombosis have been recognized as playing central roles in cardiovascular morbidity and mortality. In order to provide a conceptual framework for the use of antithrombotic therapy, the pathogenetic mechanisms underlying thrombotic events must be clearly understood. The purpose of this review is to define these mechanisms, and discuss the use of anticoagulants in both the prevention and treatment of cardiovascular diseases. PMID- 1868504 TI - Usefulness of M-mode echocardiography in the diagnosis of heart failure. AB - The utility of M-mode echocardiography in the diagnosis of heart failure (HF) was evaluated in a study of 70 patients with suspected HF (26 men and 44 women) and 63 control persons (26 men and 37 women), all aged 45-74 years. The patients were classified according to the certainty of HF diagnosis using the Boston criteria: 27 patients were defined as 'unlikely' to have HF, 19 as having 'possible' HF, and 24 as having 'definite' HF. In calculations of the sensitivities and specificities for echocardiographic variables in detecting 'definite' HF, the 95% confidence limits in the control group were used as cut-off point values. Sensitivities thus attained were 91% for mitral valve E point-septal separation (EPSS), 73% for left ventricular (LV) fractional shortening (FS), and 64% for peak rate of increase of LV diameter (PLR), respectively, and the specificities were 73, 88, and 78%, respectively. When EPSS, FS and PLR were all normal, the likelihood of 'definite' HF was as low as 7%. We conclude that M-mode echocardiography is actually a useful method in the diagnostic evaluation of patients with suspected HF, and it is more reliable in excluding than confirming the presence of HF. PMID- 1868505 TI - Early hepatitis during intravenous amiodarone administration. AB - Two patients with acute changes suggesting acute hepatitis after parenteral amiodarone administration are described. No other explanation for liver damage was found in these patients. Normalization of liver function in spite of continuation of drug infusion was observed. PMID- 1868506 TI - Analysis of a selected group of patients with acute myocardial infarction. PMID- 1868508 TI - [Radioimmunoscintigraphy in experimental and clinical tumors]. AB - Radioimmunoscintigraphy is a diagnostic method which uses labelled monoclonal antibodies for the visualization of tumourous foci. It is a nuclear medical method which is developing rapidly. The author mentions basic investigations on the bio-distribution of antibodies in animal models as well as review of contemporary clinical studies with the diagnostic use of commercial monoclonal antibodies. PMID- 1868507 TI - Sodium inhibits hormone release and stimulates calcium efflux from isolated nerve endings of the rat neurohypophysis. AB - 1. We studied the effects of extracellular sodium on the secretion of vasopressin (VP) and oxytocin (OT) and the efflux of 45Ca from isolated, perfused nerve endings of the rat neurohypophysis (neurosecretosomes). 2. Upon removal of sodium from the perfusing medium, basal release of VP and OT increased by 3.95 +/- 0.23- and 3.71 +/- 0.22-fold, respectively, followed by a decline to about double the levels in normal (150 mM) sodium (P less than or equal to 0.1). 3. Compared to neurosecretosomes perfused in normal (150 mM) sodium, omission of sodium from the medium augmented ionomycin-induced VP and OT secretion by 66 +/- 5- and 20 +/- 3 fold, respectively, and A23187-induced secretion was increased 1.3 +/- 0.4- and 1.3 +/- 0.1-fold (P less than or equal to 0.01 for both ionophores). 4. The inhibition of ionomycin-induced secretion by sodium was concentration dependent (P less than or equal to 0.01 for sodium greater than or equal to 5 mM); the IC50 was about 10 mM sodium for both hormones, and the Hill slope was close to -1. 5. The rate of 45Ca efflux from neurosecretosomes showed 2.7 +/- 0.1-fold stimulation upon increasing sodium from 4.5 to 150 mM (P less than or equal to 0.01). 6. Our results suggest that sodium inhibits basal and stimulated secretion at the nerve terminal, possibly by reducing intraterminal calcium through sodium/calcium exchange. PMID- 1868509 TI - [Are there common risk factors for the development of ischemic heart disease and colorectal carcinoma?]. AB - The author evaluates accepted risks for the genesis and development of ischaemic heart disease in relation to their incidence in patients with confirmed colorectal adenoma. These risks were investigated in 194 patients with adenoma of the large intestine and their presence was compared with a group of 200 subjects not suffering from this disease. In the investigated group with colorectal adenoma an elevated blood pressure was recorded in 98 patients (50.5%), hypercholesterolaemia in 127 (65.5%), obesity in 113 (58.3%) and smoking in 104 patients (53.6%). In the control group of 200 subjects a high blood pressure was recorded in 54 patients (27%), hypercholesterolaemia in 72 (36%), obesity in 70 patients (35%) and smoking in 101 cases (50.5%). The results are discussed with regard to possible aimed secondary prevention, as the contemporary screening of colorectal cancer by means of occult haemorrhage tests is done only up to the age of 45 years. The risk of obesity, hypercholesterolaemia and high blood pressure is found in the group with colorectal adenoma significantly more frequently, as compared with the control group not suffering from oncological disease. PMID- 1868510 TI - [Psychiatric problems in the print media in the past]. AB - The author analyzed reports on the mentally sick and psychiatry in our daily newspapers in 1909, 1928 and 1960. He analyzed the number, type, terminology and general character of the informations. In 1909 and 1928 he found a large number of references; their number and subjects were not very dependent on the type of paper nor on the year of publication. Roughly one quarter of the mentioned reports was information on the heteroaggressiveness of the mentally sick which naturally evoked negative attitudes of the public. Reports evoking positive attitudes, e.g. sympathy, were very rare. From the psychopathological aspect most frequently accounts on psychoses were found. In descriptions of the symptomatology the author did not detect any attempts of professional or pseudoprofessional accounts. In 1960 no data were found. We assume that at present when there is an increased interest in the press in psychiatric problems the historical retrospective may prove useful for the under standing of some unfavourable attitudes of the public to psychiatry as well as for possible reflections on improvement of the unsatisfactory attitude of the public to the discipline of psychiatry. PMID- 1868511 TI - [Phalloplethysmographic findings in homosexual pedophile offenders]. AB - Using phalloplethysmographic tests comprising 20 coloured slides of four categories the authors examined 50 homosexual pedophil delinquents and a matched group of heterosexual men. The findings of the two compared groups differed significantly on exposure to three categories of erotic stimuli--adult heterosexual and homosexual objects and child homosexual objects. Only on projection of child heterosexual objects there were no statistically significant differences in the number and magnitude of positive vasomotor reactions recorded in the two groups. Men in the control group responded more frequently and more positively to adult heterosexual objects than homosexual pedophil delinquents. The latter responded more frequently positively to adult and child homosexual objects. In more than one quarter of the delinquents (13 men) a preference of child objects was found, i.e. a deviant pedophil orientation. In seven men the preference of child objects was without sexual differentiation, six men preferred homosexual child objects. PMID- 1868512 TI - [Prolipase in the treatment of dyspepsia in chronic liver diseases]. AB - In 12 patients with chronic liver disease without detectable pancreatic insufficiency the authors tested in clinical trials the pancreatic enzyme preparation Prolipase (Cilag AG, Switzerland) in an attempt to influence the marked dyspeptic complaints of patients. They administered three times per day two capsules before meals for a period of three weeks. Half the patients evaluated the therapeutic effect as excellent, one quarter as very good, only one quarter did not observe a marked favourable effect on dyspepsia. Treatment was well tolerated and no undesirable side-effects were observed. Prolipase can thus be used in dyspepsias associated with chronic hepatic lesions. PMID- 1868513 TI - [Fractures of the mandibular condyle in Charles IV, a Czech king]. PMID- 1868514 TI - [The healers Appolonia and Elizabeth in old Czech art]. PMID- 1868515 TI - [Uniform health insurance--the current most advantageous form of health care financing for the population]. PMID- 1868516 TI - [Knowledge of oncology and its importance in the physician's approach to neoplastic diseases]. PMID- 1868517 TI - The efferent connections of the lateral septal nucleus in the guinea pig: projections to the diencephalon and brainstem. AB - The anterograde Phaseolus vulgaris-leucoagglutinin (PHA-L) tracing technique was used to determine the distribution of efferent fibers originating in the lateral septal nucleus of the guinea pig. For complementary detection of the chemical identity of the target neurons, double-labeling immunocytochemistry was performed with antibodies to PHA-L and to vasopressin, oxytocin, vasoactive intestinal polypeptide, serotonin or dopamine beta-hydroxylase, respectively. The hypothalamus received the majority of the PHA-L-stained septofugal fibers. Here, a specific topography was observed. (1) The medial and lateral preoptic area, (2) the anterior, lateral, dorsal, posterior hypothalamic and retrochiasmatic area, (3) the supraoptic, paraventricular, suprachiasmatic, dorsomedial, caudal ventromedial and arcuate nuclei, and (4) the tuberomammillary, medial and lateral supramammillary, dorsal and ventral premammillary nuclei always contained PHA-L labeled fibers. The rostral portion of the ventromedial nucleus and the medial and lateral mammillary nucleus only occasionally showed weak terminal labeling. In other diencephalic areas, termination of PHA-L-labeled fibers was observed in the epithalamus and the nuclei of the midline region of the thalamus. In the mesencephalon, terminal varicosities occurred in the ventral tegmental area, interfascicular and interpeduncular nucleus, and periaqueductal gray. In addition, the dorsal and medial raphe nuclei of the metencephalon, together with the locus coeruleus and the dorsal tegmental nucleus, received lateral septal efferents. PMID- 1868518 TI - The efferent connections of the lateral septal nucleus in the guinea pig: intrinsic connectivity of the septum and projections to other telencephalic areas. AB - The distribution of efferent fibers originating in the lateral septal nucleus was investigated in guinea pigs by means of anterograde tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L). Special emphasis was placed on the intraseptal fiber systems. The fibers originating from the different subnuclei of the lateral septal nucleus formed massive horizontal connections in the rostrocaudal axis. Projections to the contralateral, congruent subnuclei were also detected. In the medial septum/diagonal band of Broca complex the largest number of PHA-L-stained fibers was found after application of the tracer into the dorsal subnucleus of the lateral septal nucleus; the density of the efferent fibers decreased progressively after injection into the intermediate or ventral subnuclei. In all cases the diagonal band contained a much higher number of efferent fibers from the lateral septal nucleus than from the medial septal nucleus. In the medial septal nucleus, terminal labeling was generally sparse. Other telencephalic areas (organum vasculosum of the lamina terminalis, nucleus accumbens, bed nucleus of the stria terminalis, amygdala, hippocampal complex, and other cortical areas) contained varying numbers of labeled projections. In double-labeling experiments, a close spatial relationship between PHA-L-stained fibers and vasoactive intestinal polypeptide-immunoreactive perikarya was observed in several of these target areas. PMID- 1868519 TI - Muller glia endfeet, a basal lamina and the polarity of retinal layers form properly in vitro only in the presence of marginal pigmented epithelium. AB - Dissociated embryonic chicken retinal cells regenerate in rotary culture into cellular spheres that consist of subareas expressing all three nuclear layers in an inside-out sequence (rosetted vitroretinae). However, when pigmented cells from the eye margin (peripheral retinal pigment epithelium) are added to the system, the sequence of layers is identical with that of an in-situ retina (laminar vitroretinae). In order to elucidate further the lamina-stabilizing effect exerted by the retinal pigment epithelium, we have compared both systems, laying particular emphasis on the ultrastructure of the basal lamina and of Muller glia processes. Ultrastructurally, in both systems, an outer limiting membrane, inner segments of photoreceptors and the segregation of cell bodies into three cell layers develop properly. Synapses are detectable in a premature state, although only in the inner plexiform layer of laminar vitroretinae. Although present in both systems, radial processes of juvenile Muller glia cells are properly fixed at their endfeet only in laminar vitroretinae, since a basal lamina is only expressed here. Large amounts of laminin are detected immunohistochemically within the retinal pigment epithelium and along a basal stalk that reaches inside the laminar vitroretinae. We conclude that the peripheral retinal pigment epithelium is essential for the expression of a basal lamina in vitro. Moreover, the basal lamina may be responsible both for stabilizing the correct polarity of retinal layers and for the final differentiation of the Muller cells. PMID- 1868520 TI - The distribution of gonadotropin-releasing hormone (GnRH) neurons and fibers throughout the chick brain (Gallus domesticus). AB - Nerve fibers and perikarya containing gonadotropin-releasing hormone (GnRH-like) immunoreactivity were investigated in the brain of the three-week-old chick. Gallus domesticus using the technique of immunocytochemistry. Six major groups of perikarya were found to include the olfactory bulb, olfactory tubercle/lobus parolfactorius, nucleus accumbens, septal preoptic hypothalamic region (three sub nuclei), lateral anterior thalamic nucleus and in and about the oculomotor complex. The immunostaining was unusual in the latter group, suggesting that the neurons may contain a GnRH-II like material. Immunoreactive fibers for GnRH were found throughout the entire brain extending from the olfactory bulbs to the caudal brainstem. Two anatomical areas, not emphasized in the past literature, which had distinct GnRH-like immunoreactivity, included the lateral anterior thalamic nucleus and the preoptic recess. The former included a group of GnRH perikarya that is also known to be a retino-recipient area while the latter contained neuronal terminals some of which appeared to be contacting the cerebrospinal fluid of the preoptic recess. An attempt was made to list all anatomical structures that contained or were juxta-positioned to sites that displayed immunoreactive perikarya and fibers including circumventricular organs. PMID- 1868521 TI - Ocular distribution of 70-kDa heat-shock protein in rats with normal and dystrophic retinas. AB - Stress proteins are thought to play an important role in cellular development and in survival mechanisms. We compared the immunolocalization of the 70-kDa stress protein (SP70) in the ocular tissue of the normal Sprague-Dawley (SD) rat with that in the Royal College of Surgeons (RCS) rat with retinal dystrophy. SP70 was present in the maturing ocular tissues of both rat strains. However, once retinal degeneration began in the RCS rat, the retinal pigment epithelium and photoreceptor cells showed increased immunostaining for SP70 over that observed in age-matched SD rats. In late stages of retinal degeneration, immunostaining for SP70 was considerably reduced in the RCS retina, whereas normal distribution of immunostaining for SP70 in the SD retina was preserved, albeit decreased, through postnatal day 180. The optic nerve, ciliary body, and corneal epithelium were also influenced by the dystrophic disease condition, although the pattern of changes in SP70 immunostaining differed for each tissue. These results suggest that the genetic defect in the RCS rat produces a state of metabolic stress in all ocular tissues as the degeneration progresses, but that the subsequent rise in ocular SP70 is insufficient to prevent progression of the disease. PMID- 1868522 TI - The distribution of corticotropin-releasing factor--immunoreactive neurons and nerve fibers in the brain of the snake, Natrix maura. Coexistence with arginine vasotocin and mesotocin. AB - The anatomical distribution of neurons and nerve fibers containing corticotropin releasing factor (CRF) has been studied in the brain of the snake, Natrix maura, by means of immunocytochemistry using an antiserum against rat CRF. To test the possible coexistence of CRF with the neurohypophysial peptides arginine vasotocin (AVT) and mesotocin (MST) adjacent sections were stained with antisera against the two latter peptides. CRF-immunoreactive (CRF-IR) neurons exist in the paraventricular nucleus (PVN). In some neurons of the PVN, coexistence of CRF with MST or of CRF with AVT has been shown. Numerous CRF-IR fibers run along the hypothalamo-hypophysial tract and end in the outer layer of the median eminence. In addition, some fibers reach the neural lobe of the hypophysis. CRF-IR perikarya have also been identified in the following locations: dorsal cortex, nucleus accumbens, amygdala, subfornical organ, lamina terminalis, nucleus of the paraventricular organ, nucleus of the oculomotor nerve, nucleus of the trigeminal nerve, and reticular formation. In addition to all these locations CRF-IR fibers were also observed in the lateral septum, supraoptic nucleus, habenula, lateral forebrain bundle, paraventricular organ, hypothalamic ventromedial nucleus, raphe and interpeduncular nuclei. PMID- 1868523 TI - Organoid reorganization of human tumors under in vitro conditions. AB - In the present study we describe a new method to cultivate human tumors, which allows organoid differentiation under in vitro conditions. Diverse tumors of different origin and various histopathology which had been heterotransplanted to athymic mice were dissociated into single cells and seeded at high cell density onto a membrane filter consisting of cellulose nitrate at the gas-medium interface. Within a few days, the tumor cells reorganized and differentiated into organoid structures which exhibited the typical histological characteristics of the original tissues. Due to the formation of organoid aggregates, which was also previously seen with normal fetal cells, this type of culture has been described as 'organoid culture'. In the case of adenocarcinomas of the lung and the colon including the rectum, glandular structures with central lumina, adjacent microvilli, and junctional complexes were formed. Numerous specific intercellular contacts such as desmosomes and tight junctions occurred as well as interdigitations of adjacent cell membranes. In a tumor of the rectum, a typical brush border differentiated at the surface of the reorganized tumor-tissue aggregate. Epidermoid carcinomas of the head and neck developed structures resembling the spinous layer of the epidermis, exhibiting numerous desmosomes and intracytoplasmic bundles of tonofilaments radiating into the desmosomes. Most tumors produced a fragmentary monolayered or multilayered basal lamina of similar morphological appearance as under in vivo conditions. These results illustrate the organoid reorganization and differentiation of human tumor cells under the experimentally rather simple conditions of the organoid culture systems and clearly demonstrate that this in vitro system comes close to the in vivo situation as far as certain differentiation phenomena are concerned. PMID- 1868524 TI - Cellular subsets of the milky spots in the human greater omentum. AB - The cellular composition of the human milky spots was investigated on surgically removed specimens of the greater omentum of three 8-month-old infants operated on for neuroblastoma. Monoclonal antibodies and immunohistochemical methods for recognition of macrophages. B-lymphocytes and T-lymphocytes and toluidine-blue staining for mast cells were used. The mean number of cells in one milky spot amounted to 570 +/- 33. This cell population was composed of 47.5% macrophages, 29.1% B-lymphocytes, 11.7% T-lymphocytes and 6.1% mast cells. Since inflammation was absent in the material investigated, the numerical data found in the present paper could be regarded as representative cell levels of normal milky spots. PMID- 1868525 TI - Clinical factors affecting the immediate outcome of PTCA in patients with unstable angina and poor candidates for surgery. AB - Percutaneous Transluminal Coronary Angioplasty (PTCA) has been successfully applied in unstable angina to carefully selected patients. In this study, PTCA was performed in 277 consecutive patients suffering from unstable angina and for whom bypass surgery was not a valid alternative because either of inoperable conditions or of emergency, or because surgery was not the best option. All patients were admitted first to the intensive care unit where an attempt was made to control unstable angina under conventional medical therapy using at least iv nitroderivative, heparin, and calcium blockers. After a standardized preparation PTCA was performed either as an emergency procedure in medically refractory unstable angina (107 cases) or as an elective procedure in controlled situations after a 7 to 10 days symptom-free period. Three hundred fifty-three coronary vessels were attempted. Results of this group are compared with those of a control group made of 670 consecutive stable patients recruited during the same period, and clinical characteristics are envisaged as potential predictive factors. Unstable angina is undoubtedly associated with a higher overall complication rate, but the immediate outcome is strongly affected by the clinical context. As an example, respective success and mortality rates are: 93% and 0% when a full revascularization is attempted; 91% and 0% in elective procedures in patients under 60; 87% and 1.2% in elective PTCA for multiple vessel disease; 80% and 6.5% in emergency PTCA; 80% and 11% in the overall triple vessel disease; 84% and 16% in patients with deeply altered ejection fraction; and 58% and 26% in triple vessel disease with 2 previously occluded coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868526 TI - Effects of rapid volume expansion on the right filling pressures after prosthetic valve surgery. AB - The effects of rapid intravascular volume expansion were studied in 12 patients, 4 to 14 years after single prosthetic heart valve replacement. The data observed showed a statistically significant mean difference before and after volume expansion of right atrial mean pressure and right ventricular end diastolic and pulmonary capillary pressures. However, right atrial and pulmonary capillary pressures equilibration was not detected. The right atrial pressure form showed abnormal variations during inspiration. Dip and plateau right ventricular diastolic pressure configuration was recorded in 6 patients after expansion, was absent in 2 and questionable in 4. A deep Y descent with an M-shaped right atrial pressure form was recorded in all 12 patients. The explanation for these phenomena is unclear. Thus, in the absence of pressure equilibration and clinical evidence of constriction, the abnormalities recorded during rapid volume expansion should be cautiously interpreted. PMID- 1868527 TI - Fluoroscopic guidance in transseptal catheterization for percutaneous mitral balloon valvotomy. AB - A percutaneous mitral balloon valvotomy (PMBV) was attempted on 190 patients with fluoroscopic guidance of atrial septal puncture for transseptal catheterization; in 3 cases, the procedure could not be performed. The left atrium was always reached on the first attempt, when the relationship of the Brockenbrough needle to the aortic catheter was previously observed in 3 fluoroscopic views: anteroposterior, 45 degrees right anterior oblique, and lateral. The atrial septal puncture site was located immediately below the aortic valve level, probably in the fossa ovalis, for the first 80 patients, and at mid distance between the aortic valve level and the diaphragm for the last 110. Hemodynamic data were similar in both groups. Fluoroscopic guidance for atrial septal puncture seemed capital for patients with scoliosis or in whom a vascular distortion (e.g., advanced pregnancy, right inferior vena cava absence) prevented a perfect parallelism between the needle curve and the needle outer index. PMID- 1868528 TI - Cardiac tamponade following coronary arterial rupture during coronary angioplasty. AB - We describe a patient in whom percutaneous transluminal coronary angioplasty (PTCA) was complicated by rupture of the left anterior descending coronary artery (LAD) with pericardial tamponade. The outcome was favorable with drastic intervention which included: occlusion of the bleeding vessel with the PTCA balloon, pericardiocentesis, and ligation of the vessel without the need of aortocoronary bypass graft. PMID- 1868529 TI - Dislodgement of a vein graft thrombus by angiographic injection of native coronary artery. AB - A case of retrograde dislodgement of thrombus in a saphenous vein graft during injection of the native right coronary artery is presented. Attention to this previously undescribed complication may allow for timely treatment with emergency surgery or thrombolysis. PMID- 1868530 TI - Cor triatriatum dexter: recognition and percutaneous transluminal correction. AB - Cor triatriatum dexter is a rare congenital anomaly in which an obstructive membrane is located in the right atrium. The detection usually occurs after the sequelae of systemic congestion, coagulopathy, and hepatic dysfunction have set in, leading up to a high surgical risk. A percutaneous balloon correction of cor triatriatum dexter in a patient with advanced right-sided congestive symptoms and hepatic dysfunction is presented. This efficacious method is an alternative to surgical correction and could be extended to the more common cor triatriatum sinistra. PMID- 1868531 TI - Holmium laser angioplasty after failed coronary balloon dilation: use of a new solid-state, infrared laser system. AB - A new solid-state laser system was used in a case of saphenous vein graft occlusion untreatable by standard very low-profile balloon angioplasty. The 2100 nm infrared pulsed thulium/holmium: YAG laser successfully recanalized an obtuse marginal bypass graft without complications. The holmium laser has several advantages over excimer systems and may prove an effective adjunct or alternative to coronary balloon angioplasty. PMID- 1868532 TI - Congenital atresia of left main coronary artery: proposed mechanism for severe disabling angina in a patient with non-atherosclerotic single right coronary artery--a case report. AB - A patient with progressive disabling angina was found to have a single right coronary artery with atresia of the left main coronary artery, and absence of any obstructive coronary disease. The patient required aortocoronary by-pass surgical reconstruction of a left main coronary artery to control her angina. Possible mechanisms for the development of her anginal pain are briefly discussed. PMID- 1868533 TI - Total occlusion of the circumflex artery with collateral supply from the conus artery. AB - The conus artery has long been recognized as an important source of collateral blood supply to a significantly diseased left anterior descending artery. This artery which arises 50% of the time from a separate orifice in the right sinus of Valsalva may also provide collateral circulation to a diseased right coronary artery. To date, there have been no reported instances of the conus artery supplying collateral flow to a totally occluded circumflex artery. In this report we describe such a case in a patient with severe three vessel disease. The implications of such a finding in patient management are also discussed. PMID- 1868534 TI - Unrecognized stenosis by angiography documented by intravascular ultrasound imaging. AB - This report documents how intravascular ultrasound imaging was used to diagnose a short "napkin-ring" stenosis that was missed by coronary angiography. Intravascular ultrasound revealed a lumen of 2.6 x 2.5 mm in diameter and 5.0 mm2 in cross-sectional area, with a residual atheroma that occluded 63% of available cross-sectional area at the stenosis. PMID- 1868535 TI - Anomalous origin of the sinus nodal artery from left main artery. PMID- 1868536 TI - Angioplasty of an oversized venous bypass graft using two fixed wire systems. AB - Oversized saphenous vein bypass grafts may be inadequately dilated using currently available coronary angioplasty catheters. The hugging balloon technique has been previously described for lesions in large saphenous vein grafts. We report the initial use of the hugging balloon technique using two fixed wire angioplasty catheters in an oversized saphenous vein graft. PMID- 1868537 TI - Long-term patency of arterialized cephalic vein used as a conduit for coronary artery bypass grafting. PMID- 1868538 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: the left-sided V wave. AB - The left-sided V wave is dependent on both left atrial and ventricular pressure/volume filling relationship. The cardiac rhythm and timing of atrial systole also influences the V wave. The morphology of the V wave can reflect the severity of mitral regurgitation with stenosis, but valve areas in this setting may be better assessed by a pressure half-time method. Finally, as queried in our first patient example, V wave alternans is a reflection of left ventricular pressure alternans in a failing heart. Other signs of poor left ventricular function in Figure 1 also included an elevated minimal diastolic pressure and markedly elevated left ventricular end diastolic pressure. Hemodynamic findings of poor left ventricular function will be addressed in detail in a later "Rounds." PMID- 1868539 TI - Evaluation of a theoretical Doppler index to noninvasively estimate peak dP/dt using continuous wave Doppler ultrasound of ascending aortic flow in man. AB - A theoretical formula for calculation of peak dP/dt was derived using parameters obtained from continuous wave Doppler echocardiography signals of aortic blood flow. The direct proportional relationship between the main variables of this formula and invasively measured peak dP/dt was validated in 20 patients undergoing routine diagnostic cardiac catheterization. Doppler signals of aortic flow were obtained simultaneously to invasive pressure recordings with a 2 MHz continuous wave transducer via the suprasternal echocardiographic window. The Doppler signals were recorded on magnetic tape and measurements were made with digital calipers by two independent, blinded observers. The following parameters were measured: peak velocity (V) and time from onset of ejection to peak velocity (T). V2/T, the variable of the derived formula, was calculated for each of the observer's measured parameters and showed a very high interobserver correlation. The two observers' measurements of each parameter were averaged for each patient and the resulting mean was used in calculating the V2/T and mean acceleration. 4. A good correlation of V2/T with invasively measured peak dP/dt was obtained. Our derived index of left ventricular function showed a higher correlation with peak dP/dt compared to other Doppler indices of ventricular function. V2/T may provide a noninvasive method for estimating peak dP/dt. PMID- 1868540 TI - Double balloon mitral valvuloplasty via a single transseptal puncture. PMID- 1868541 TI - Coronary angioplasty of septal perforator arteries. PMID- 1868542 TI - Anomalous origin of the left main coronary artery. PMID- 1868543 TI - Transcriptional control--lessons from an E. coli promoter data base. PMID- 1868544 TI - Correction: an inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers. PMID- 1868545 TI - Correction: the peptidyl-prolyl isomerase, FK506-binding protein, is not identical to protein kinase C inhibitor 2. PMID- 1868546 TI - Centromere-dependent binding of yeast minichromosomes to microtubules in vitro. AB - We present an in vitro assay for yeast centromere function; isolated yeast minichromosomes require a functional centromere to bind to bovine microtubules and sediment with them. Centromere-bovine microtubule complexes form at physiological microtubule concentrations. Two of the three centromere DNA elements, which are necessary for centromere function in vivo, are also necessary for centromeres to bind microtubules in vitro. However, purified centromere DNA alone does not bind to microtubules. These results suggest that microtubule binding must be mediated by the two centromere DNA elements and factors that associate with one or both of them. The percent of centromeres with microtubule binding activity is 7- to 10-fold higher in lysates made from nocodazole-arrested G2-M cells than from alpha factor G1 cells, suggesting that this centromere activity is regulated during the cell cycle. The potential of this assay for dissecting centromere assembly, function, and regulation is discussed. PMID- 1868547 TI - Evidence for a functional link between profilin and CAP in the yeast S. cerevisiae. AB - CAP is a component of the S. cerevisiae adenylyl cyclase complex. The N-terminal domain is required for cellular RAS responsiveness. Loss of the C-terminal domain is associated with morphological and nutritional defects. Here we report that cap cells bud randomly and are defective in actin distribution. The morphological and nutritional defects associated with loss of the CAP C-terminal domain are suppressed by over-expression of PFY, the gene encoding profilin, an actin- and polyphosphoinositide-binding protein. The phenotype of cells lacking PFY resembles that of cells lacking the CAP C-terminal domain. Study of mutated yeast profilins and profilins from Acanthamoeba suggests that the ability of profilin to suppress cap- cells is dependent upon a property other than, or in addition to, its ability to bind actin. This property may be its ability to bind polyphosphoinositides. We propose that CAP and profilin provide a link between growth signals and remodeling of the cellular cytoskeleton. PMID- 1868548 TI - Kinetics and efficacy of positive selection in the thymus of normal and T cell receptor transgenic mice. AB - DNA-labeling studies in alpha beta T cell receptor (TCR) transgenic mice show that the lifespan of immature CD4+8+ thymocytes is 3.5 days irrespective of whether they are selected for maturation or not. While nonselected cells die, the binding of the TCR to thymic major histocompatibility complex molecules rescues CD4+8+ cells from programmed cell death and induces first upregulation of the TCR level and then differentiation into CD4+8- or CD4-8+ cells in the absence of any cell division. When most CD4+8+ thymocytes express a selectable transgenic TCR the formation of mature cells with high TCR levels is 10-20 times as efficient as observed in normal mice, yet still only 20% of the CD4+8+ cells become mature. This is due to the limited availability of selecting 'niches': most CD4+8+ thymocytes with a selectable transgenic TCR will undergo maturation when they represent only 5% or less of all CD4+8+ cells. PMID- 1868549 TI - A novel endopeptidase from Xenopus that recognizes alpha-helical secondary structure. AB - The magainin peptides of Xenopus laevis are broad-spectrum antimicrobial agents. Upon discharge from the skin glands, these basic, amphipathic peptides are each further processed at a single Xaa-Lys bond into half-peptides by a cosecreted protease. We describe the characterization and purification to homogeneity of this endopeptidase from Xenopus skin. The enzyme is a metalloprotease 110 kd in size. Analyses of substrate specificity revealed that the endopeptidase recognizes peptides that share the ability to adopt an amphipathic, alpha-helical motif composed of at least 12 residues, with one face strongly hydrophobic. Cleavage occurs on the amino side of a specific lysine that must be precisely positioned relative to the hydrophobic face of the alpha helix. This enzyme, which we propose to call "magaininase," represents a novel class of endopeptidases that hydrolyzes peptides on the basis of specific secondary structure rather than primary amino acid sequence. PMID- 1868550 TI - Drug delivery to the brain using polymers. AB - The delivery of drugs to the brain has been a major challenge to the scientist developing drugs designed for central nervous system (CNS) activity. One of the obstacles to the progress is the transport of drug through the blood brain barrier (BBB). The criteria for effective drug delivery to the CNS include the following: (a) the drug must have access to the brain, (b) the effect of the drug should be localized, (c) the drug must be stable, and (d) the effective dose should be sustained and controlled. To meet some of the above criteria, two approaches have been used: systemic administration of drugs, and direct delivery of drugs into the brain. The systemic administration of drugs relies on passive diffusion of drug through the BBB, formation of lipid soluble prodrugs and the use of monoclonal antibodies for targeting the drug to the CNS. The other approach includes the use of implantable polymer systems and infusion pumps. Both of the approaches have some advantages and disadvantages. Because of the enormous amount of literature on drug delivery to the brain, the following review focuses on the use of polymer-based implantable systems. The review includes nondegradable and biodegradable polymer implants from the conceptual phase to the clinic. PMID- 1868551 TI - Chemoembolism in cancer chemotherapy. PMID- 1868553 TI - Arthroscopy update. PMID- 1868552 TI - Microencapsulation of drugs by pan and air suspension techniques. AB - This review examines recent advances in the commercial production of microencapsulated drug products. Factors influencing drug selection are considered with particular reference to the design of controlled drug delivery systems. The formulation of both aqueous and nonaqueous coating materials is discussed with examples of common problems encountered in applied coatings and ways to overcome same. Methods of core production are considered with emphasis on spheronization procedures. Pan and air suspension techniques, together with modification thereof, are discussed. Certain newer in vitro procedures such as scanning electron microscopy with energy dispersive analysis or topographical plots of dissolution data for complex microencapsulated systems are presented. Finally aspects of the stability and in vivo testing of microencapsulated products are considered in the context of requirements for regulatory approval. PMID- 1868554 TI - A technique for arthroscopic anterior cruciate ligament repair. AB - Treatment options for anterior cruciate ligament (ACL) tears include rehabilitation therapy, derotation therapy, and surgical repair or reconstruction. This article presents an arthroscopic technique for reattaching the ACL that offers some advantages over other procedures. Advantages include avoiding exposure of the knee joint, improved cosmetic results, and reduced recuperation time. PMID- 1868555 TI - Anterior cruciate ligament reconstruction with autografts. AB - Arthroscopically assisted ACL reconstruction has undergone rapid development in recent years. Although achievement of stability has been well-documented in open ACL reconstructive procedures, improved results may be obtained by reducing operative morbidity. Arthroscopically assisted ACL reconstruction appears to offer significantly diminished morbidity and thus offers more predictable rehabilitation, at least initially, after surgery. Improvements in instrumentation continue to refine the precision of this technique. Proper graft selection is an important issue that is paramount to the evolution of ligament reconstruction surgery. Although the central third patellar tendon is presently the operation by which all new techniques must be compared, the use of nonautogenous grafts may complement arthroscopic reconstruction by allowing further reduction in surgical morbidity. In this article we have expanded on some of the advantages of arthroscopic ACL reconstruction, given an overview of arthroscopic techniques, and described the techniques we prefer. PMID- 1868556 TI - Allograft reconstruction of the anterior cruciate ligament. AB - This article reviews the scientific basis for the use of allografts in reconstruction of the anterior cruciate ligament of the knee. The possibility and incidence of postsurgical rejection and disease transmission with allograft usage are discussed. The operative technique of the author and the rationale for his postoperative rehabilitation protocol is explained. PMID- 1868557 TI - Posterior cruciate ligament injuries. AB - PCL reconstruction is not often necessary. Arthroscopic techniques using autograft or allograft substitution for the PCL probably bear more physiologic and anatomic likeness to the normal ligament than to tissue transfers posteriorly. The arthroscopic procedure is exacting and technically demanding. It is advisable to supplement the PCL reconstruction with an appropriate capsulorrhaphy when the posterior capsule, arcuate complex, or oblique popliteal ligament are also injured. In combined cruciate injuries, PCL reconstruction is notably easier when staged before reconstruction of the ACL. PMID- 1868558 TI - Meniscal repair. AB - Over the past several decades, scientific evidence has mounted to substantiate the vital role of the meniscus in the function of the knee. Total meniscectomy is rarely indicated and the pendulum of orthopedic popular opinion has swung toward new ways to preserve the injured meniscus. This article reviews the anatomy, blood supply, and function of the meniscus and also discusses the supporting scientific evidence, decision-making processes, and techniques for meniscal repair. PMID- 1868560 TI - Osteochondritis dissecans. AB - Osteochondritis dissecans is a rare orthopaedic disorder of unknown etiology. Advances in CT and MRI scanning have increased our knowledge of the disorder, but arthroscopy remains the principle means of monitoring its progress. Arthroscopic surgery has displaced traditional arthrotomy in many instances and is useful in retrieval of loose bodies, drilling of osteochondral fragments, retrograde bone grafting, and abrasion arthroplasty. Arthrotomy continues to be the best method of pinning and bone grafting of detached lesions. Advances in transplant surgery now permit large craters to be patched with osteochondral allografts. PMID- 1868559 TI - Patellofemoral pain. An arthroscopic perspective. AB - Patellofemoral pain should be approached as thoroughly as any other musculoskeletal disease. A careful patient history and physical examination are mandatory. These are followed by appropriate imaging studies such as radiographs, bone scans, CT scans, CT arthrograms, and MRI, as each individual case demands. Finally, arthroscopy is employed in its proper sequence. This article has been developed as an attempt to define a classification scheme of anterior knee pain and then to narrow this down to pain localized to the patellofemoral joint. The authors have attempted to isolate further the clinical entities to those that can be diagnosed and treated arthroscopically. Arthroscopy and arthroscopic surgery allow recognition and treatment of these disorders with minimal invasiveness and patient morbidity. PMID- 1868561 TI - Rotator cuff lesions. Acute and chronic. AB - The complex anatomy of the shoulder often impedes the orthopedic surgeon's evaluation and understanding of injuries to the shoulder joint, particularly the rotator cuff muscle-tendon complex. Arthroscopy, MRI, and digital data analysis are several techniques now at the surgeon's disposal. This article reviews the application of these techniques in the evaluation of rotator cuff injuries. PMID- 1868562 TI - Weight lifting. Risks and injuries to the shoulder. AB - The weight lifter's desire to achieve higher limits of performance coupled with the rotator cuff's unfavorable position during lifting often leads to shoulder injury. Proper lifting techniques and training habits could reduce the risk of injury. When chronic symptoms occur, however, arthroscopy can help diagnose the injury, and arthroscopic procedures for injuries such as rotator cuff chronic tendinitis and incomplete tears, and biceps tenosynovitis can be performed. PMID- 1868563 TI - The prone position for elbow arthroscopy. AB - Using the prone position for diagnostic and therapeutic arthroscopy improves intraoperative stability of the arm and allows the surgeon to approach the joint in a more intuitive manner. With this position, indications for elbow arthroscopy are increased and risks to neurovascular structures are reduced. Access to the posterior chamber is facilitated when the patient is in a prone position. This article describes both this arthroscopic technique and portal anatomy. PMID- 1868564 TI - Arthroscopic treatment of Panner's disease. AB - Panner's disease, or osteochondrosis of the capitellum, may actually be a continuum of disorders. In the past, such lesions were treated conservatively with surgery as a final option. With the advent of arthroscopy, a diagnosis can be made, and treatment with limited invasiveness instituted. This article reviews the diagnostic and therapeutic advantages of arthroscopic techniques in the treatment of Panner's disease. PMID- 1868565 TI - Lesions of the posterior compartment of the elbow. AB - This article examines the diagnosis and treatment of lesions of the posterior compartment of the elbow, along with the anatomy and biomechanics of the elbow of the throwing athlete. An indepth evaluation of specific lesions and a detailed description of elbow arthroscopy are also presented. PMID- 1868566 TI - Chronic and recurrent ankle sprains. AB - Persistent symptoms such as pain, swelling, or giving way after lateral ligament injuries of the ankle are not uncommon. The treating orthopedist must first decide whether the symptoms are related to the ankle instability. Intra-articular or extra-articular injury may occur concomitantly with either a stable or unstable ankle, and careful diagnostic evaluation must be undertaken. Arthroscopy of the unstable ankle in which there is significant pain without demonstrable intra-articular injury by bone scans, CT scans, and MRI studies is indicated, as intra-articular lesions do occur that may result in chronic pain after the ankle has been rendered stable. An arthroscopic lateral ankle capsulodesis procedure has been described with promising early results. Arthroscopic management of an intra-articular pathologic condition in the stable ankle involves removal or excision of offending bone and/or soft tissue. Patients' symptoms can be improved significantly by these approaches, after which there can be a return to a more normal level of function. PMID- 1868567 TI - Meniscoid lesions of the ankle. AB - The frequent use of arthroscopy has increased the orthopedic community's awareness of meniscoid lesions of the ankle and its ability to treat these lesions. This article defines the pathologic lesion and reviews the literature and case reports. PMID- 1868568 TI - Arthroscopic management of transchondral talar-dome fractures (osteochondritis dissecans) and anterior impingement lesions of the ankle joint. AB - Transchondral talar-dome fractures can be disabling conditions requiring surgical management. Arthroscopic surgery of the ankle offers a means of correcting these problems with low morbidity. A technique for performing this surgery utilizing a new noninvasive distraction device is reviewed in this article. PMID- 1868569 TI - Plasmid functions involved in the stable propagation of the pKD1 circular plasmid in Kluyveromyces lactis. AB - Plasmid factors involved in the stable propagation of pKD1-derived vectors in Kluyveromyces lactis transformants have been identified. Three genes (A, B and C) have been found to be present in pKD1: the interruption of the B and C genes led to high plasmid instability. Stability could be restored in trans when host cells contained pKD1 as the resident plasmid (pKD1+ strains). The A gene, which codes for a site-specific recombinase, did not affect plasmid partitioning. Vectors bearing only the pKD1 replication origin (or a chromosomal ARS), and no other pKD1 sequence, were very unstable both in the presence and absence of the resident plasmid in host cells. These vectors could be stabilized in pKD1+ strains, but not in pKD1 degree strains, by the insertion of a 200 bp-long pKD1 sequence. This sequence, called the cis-acting stability locus (CSL), together with the products of the B and C genes, ensured plasmid partitioning at cell division. Possible hairpin structures and direct repeats were regularly spaced within the CSL. This region, and the corresponding cis-acting stabilizing elements of other yeast plasmids, did not have sequence homology but shared some structural regularities. PMID- 1868570 TI - Mitochondrial genome of Saccharomyces douglasii: genes coding for components of the protein synthetic apparatus. AB - Mitochondrial genes coding for some components of the protein synthetic apparatus in S. douglasii have been studies in detail. A region containing stretches of high homology to the S. cerevisiae tRNA synthesis locus (TSL) and the tRNA(fmet) gene has been identified and sequenced. The organization of this region was very similar to that present in S. cerevisiae, including the presence of a possible transcription starting signal. The S. douglasii TSL gene is shorter due to several deletions which, however, do not involve the regions coding for RNA domains know to be required for the catalytic activity of mitochondrial RNAse P. The S. douglasii LSU rRNA gene has been shown to contain a typical group I intron highly homologous to its S. cerevisiae counterpart, except for the absence of the open reading frame which in S. cerevisiae codes for I-SceI endonuclease. PMID- 1868571 TI - The Chlorella H+/hexose cotransporter gene. AB - The complete genomic sequence of the inducible Chlorella kessleri H+/hexose cotransporter (HUP1) has been obtained from two overlapping clones isolated from a lambda gt10 library. The HUP1 gene is interrupted by 14 introns with the first intron being located in the 5'-untranslated part of the gene. The average intron length is 220 bp, yielding a very regular intron/exon pattern in the gene. The codon usage in this gene is strongly biased with a clear preference for C and a strong suppression of A. A consensus sequence for a putative algal polyadenylation sequence is shown and compared with other algal cDNA sequences. PMID- 1868572 TI - Chromosome rearrangements in improved cephalosporin C-producing strains of Acremonium chrysogenum. AB - A number of A. chrysogenum strains from a lineage improved in cephalosporin C production were analysed by contoured-clamped homogeneous electric field gel electrophoresis (CHEF). Although antibiotic titre was increased across the lineage, chromosome rearrangements were only observed at two points in it. In one member of the lineage the chromosomal changes included those which altered the size of the chromosome on which the isopenicillin N synthetase gene (pcbC) was located. It is proposed that chromosome changes are a chance event in an industrial strain improvement programme. PMID- 1868573 TI - Interactions between chromosomal omnipotent suppressors and extrachromosomal effectors in Saccharomyces cerevisiae. AB - Chromosomal omnipotent suppressor mutations recovered in psi+ strains of Saccharomyces cerevisiae were brought into psi- cytoplasm. SUP46, SUP138 and SUP139 acted as dominant omnipotent suppressors in the psi- cytoplasm though their suppressor activity was substantially reduced. SUP46 and SUP138 conferred recessive thermosensitivity and antibiotic sensitivity in psi- cytoplasm as in psi+ cytoplasm. On the other hand, sup111 through sup115, which acted as recessive omnipotent suppressors in the psi+ cytoplasm, manifested no, or very low, suppressor activity in the psi- cytoplasm. They, however, still enhanced the efficiency of the SUP29 tRNA suppressor in psi- cytoplasm. A multicopy plasmid carrying the wild-type SUP35 gene enhanced the efficiency of sup111 in psi- cytoplasm. PMID- 1868574 TI - Thiamine in Schizosaccharomyces pombe: dephosphorylation, intracellular pool, biosynthesis and transport. AB - We have investigated the thiamine metabolism in Schizosaccharomyces pombe and shown that: (1) Thiamine-repressible acid phosphate, coded for by the gene pho4, dephosphorylates thiamine phosphates indicating that the enzyme acts as a thiamine phosphate phosphatase. (2) In vivo synthesized thiamine is present intracellularly mainly as thiamine diphosphate. Starving cells for glucose decreases the intracellular thiamine pool. (3) The genes thi2, thi3 and thi4 control thiamine biosynthesis and probably code for thiamine biosynthetic enzymes. Thi3, which is involved in the synthesis of the pyrimidine moiety of the thiamine molecule, is allelic to the thiamine repressible gene nmt1. (4) Thiamine uptake is a thiamine regulated process, probably occurs by active transport and is controlled by the gene ptr1. PMID- 1868576 TI - Genetic analysis of Aspergillus niger mutants defective in benzoate-4-hydroxylase function. AB - This study was prompted by the observation that an Aspergillus niger transformant with a multicopy bphA (benzoate-4-hydroxylase gene) insert did not grow on benzoate, whereas a transformant with only one extra copy could grow. Therefore, an extensive survey has been made for other genes involved in the conversion of benzoate into 4-hydroxy-benzoate. A transformant with two copies of the bphA gene was used in part of the mutation experiments in order to avoid the isolation of many bphA mutants. Filtration enrichment was used to isolate mutants defective in the conversion of benzoate. The Bph mutants that have been isolated belong to six complementation groups. Mutants with a defected structural gene (bphA) were again predominantly found but, in addition, five other groups of mutants that could not grow on benzoate were isolated. Genetic analysis of the mutants showed that the six genes were localized in different parts of the genome. This was used as an additional proof that some mutants involved different genes. Diploids with seven copies of the bphA gene and heterozygous for one of the other bph genes were constructed. No indication has been obtained that any one of the mutant classes is responsible for the growth-limiting factor in bphA multicopy transformants. This study shows that the p-hydroxylation of benzoate is very complex, although the metabolic pathway is straight forward. PMID- 1868575 TI - Sequence analysis of the ARG7 gene of Schizosaccharomyces pombe coding for argininosuccinate lyase. Expression of the gene in Saccharomyces cerevisiae. AB - The complete nucleotide sequence of the ARG7 gene, coding for argininosuccinate lyase (EC 4.3.2.1), in the fission yeast (Schizosaccharomyces pombe) has been determined. It consists of an open reading frame of 461 codons. The deduced protein has a molecular weight of 51,200 Da. The gene is devoid of introns which is confirmed by the fact that it is expressed in Escherichia coli after spontaneous insertion of a bacterial sequence probably bearing a prokaryotic promoter. A perfect "TATA" box is found at -72 and the major transcription initiation site in Saccharomyces cerevisiae is located at -11 as shown by primer extension experiments. Comparison of the S. pombe lyase with related proteins from other organisms reveals an important degree of conservation except in the carboxyterminal part of the polypeptide. Additionally, a deletion removing 66 amino acids of the carboxy terminus yields an enzyme exhibiting some biological activity. A unique 1,500 b transcript was found in S. cerevisiae when the intact gene was present, but the deleted version of the gene gave rise to at least three transcripts of 1,800, 2,800 and 3,900 b. PMID- 1868577 TI - Characterization of a cDNA encoding a PSII-associated chlorophyll a/b-binding protein (CAB) from Chlamydomonas moewusii fitting into neither type I nor type II. AB - A full-length 1010-bp cDNA clone from Chlamydomonas moewusii coding for the precursor of a chlorophyll a/b-binding protein (CAB) was characterized. Northern analysis shows hybridization to a single 1150-base light-stimulated mRNA. Complementary hybrid-selected mRNAs were translated in vitro; SDS-PAGE indicates the synthesis of three polypeptides of 25, 27 and 28 kDa. Comparison of the deduced polypeptide sequence with other published CABs reveals greater similarity with PSII-associated proteins but, as with other algal CABs, our sequence does not meet established criteria for inclusion into either type I or type II, so branching of CABs into two types seems to have occurred after the divergence between algae and land plants. PMID- 1868579 TI - Mismatch-stimulated plasmid integration in yeast. AB - A single base pair mismatch (G:T or A:C) in the CYC1 gene of the integrative plasmid pAB218 stimulates up to a five-fold integration into the yeast chromosome. Analysis of chromosomal sites of plasmid integration suggests that the mismatch-stimulated integration is not targeted as would be expected if crossovers, localised in the region of the mismatch, were a necessary step in mismatch repair. Instead, the observed mismatch-stimulated plasmid integration could be due to potentially recombinogenic structures formed during mismatch repair, such as single-stranded gaps or denatured DNA regions extending around the plasmid molecule. PMID- 1868578 TI - Unusual organization of a ribosomal protein operon in the plastid genome of Cryptomonas phi: evolutionary considerations. AB - The region of the plastid genome containing the genes for ribosomal proteins S12 and S7 and the elongation factor Tu (corresponding to three of the four str operon genes of Escherichia coli) was investigated in the unicellular marine alga Cryptomonas. Sequence analysis shows the gene organization to be rps12-60 bp spacer-rps7-68 bp spacer-tufA. No introns are present in any of the genes. Comparisons of the deduced amino acid sequence of these genes with homologues from other organisms show rps12 to be very highly conserved, except at the amino terminus, and rps7 and tufA to be less well-conserved. Transcript analysis suggests that these genes are co-transcribed along with several up and/or down stream genes. The evolutionary significance of this unique gene organization is discussed. PMID- 1868580 TI - Trends in gonorrhea in Canada: 1980-1989. PMID- 1868581 TI - Outbreak of gastroenteritis associated with drinking well water--British Columbia. PMID- 1868582 TI - Food and waterborne viral outbreaks in Canada and the United States. PMID- 1868583 TI - [Activity of the community general practice physician]. AB - The author investigated the primary therapeutic and preventive care of the population provided by the health community doctor, focused on subjects above 60 years of age. A time study of the basic activities during the patient's visit in the surgery of the health community doctor was made. It was found that most care is provided by the health community doctor to subjects under 44 years and those aged 60-74 years. Most time is needed for care of women of advanced age. PMID- 1868584 TI - [The character of Dr.Vilem Hons. Facts and thoughts on the occasion of a 100 year anniversary]. AB - In the history of the Medical Faculty of the Comenius University in Bratislava there are two personalities with great merits as regards the foundation and development of the Physiology department, both pupils of professor Mares--prof. MUDr. A. Hanak and prof. MUDr. V. Hons. Professor Hons to whom this article is devoted worked in Bratislava from 1930 to 1939. He influenced in an important way the development of the Institute of Physiology in the second decade of its existence and made significant advances in the field of teaching and research. As dean of the medical faculty in 1936-37 and assistant dean in 1937-38 he helped the Faculty to resolve some complicated problems; he opposed the pressure of the undemocratic forces and established and reinforced his relations with students in particular their most important organization--The Society of Czechoslovak Medical Students. PMID- 1868585 TI - [Long-term evaluation of the relation of demographic and health indicators to drug utilization]. AB - Indicators of demographic and medical statistics display different relationships at the level of drug consumption and from these relationships different potential influences may be derived. The relationship is expressed exactly and because it develops with time its developmental trends are analyzed on a nation-wide scale in the course of 17 years. The period of analysis permits to formulate some conclusions on the stability of this relationship with regard to individual essential factors. PMID- 1868586 TI - [Education in social medicine]. AB - During the elaboration and definition of new concepts of medicine and the health services at a time of decisive social changes attention is also paid to social medicine. Its contents reflected during the past 40 years the influence of political and ideological structures and this had an adverse effect on its development, activities and prestige. Because of its importance and greater impact at present it must find its firm place also in the sphere of training at medical faculties. The author uses as a basis the present position and seeks solution in a greater integration of its components which must include also social oecology. Its coordinating activity must be mentioned more systematically also in clinical subjects. All this is to serve its more marked identity in the teaching process at medical faculties. PMID- 1868587 TI - [The microcomputer in the office of the community pediatrician]. AB - The material submitted is a draft model system for the use of a microcomputer in the daily working activity of the community paediatrician. His work comprises preventive and therapeutic care of children and he has specific tasks and specific orientation on different age groups and the ensuing administrative work. The introduction of the information system in the surgery gives an idea of its asset for the user. PMID- 1868588 TI - [Realistic possibilities of utilization of a personal computer in the office of a general practitioner]. AB - In May 1990 work on the programme "Computer system of the health community doctor Mic DOKI was" completed which resolves more than 70 basic tasks pertaining to the keeping of health documentation by health community doctors; it resolves automatically the entire administrative work in the health community, makes it possible to evaluate the activity of doctors and nurses it will facilitate the work of control organs of future health insurance companies and contribute to investigations of the health status of the population. Despite some problems ensuing from the contemporary economic situation of the country, the validity of contemporary health regulations and minimal training of our health personnel in the use of personal computers computerization of the health community system can be considered an asset to the reform of the health services which is under way. PMID- 1868589 TI - [Do we need predictions for health care expenditures?]. AB - The unfavourable health status of our population is generally known, its improvement being one of the basic prerequisites for the further development of our society. To a certain extent improvement may be promoted by high standard health services. The standard of these services depends, in addition to effective use of available financial means, on the increase of the total volume of financial resources for the health services. For a qualified decision on the actual volume of financial resources it will be necessary to have a well elaborated prognosis of expenditure on health services which among others will justify the financial demands of the branch. The prognosis of expenditure on health services will be a socio-economic prognosis which may be started in the near future, if suitable conditions will be created. PMID- 1868590 TI - Motivation for developing optical sensors for blood electrolyte measurements. PMID- 1868591 TI - Amniotic fluid phospholipid "analysis"? PMID- 1868592 TI - Serum profiles of steroid hormones in patients with Cushing's syndrome determined by a new HPLC/RIA method. AB - We developed a method for simultaneously measuring steroid hormones in very small volumes of serum, using a combination of high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). By this method, aldosterone, cortisol, 11 deoxycortisol, estrone, estradiol, androstenedione, dehydroepiandrosterone, deoxycorticosterone, 17-hydroxyprogesterone, testosterone, pregnenolone, and progesterone could be determined in a single 100-microL aliquot of serum from normal adults and patients with Cushing's syndrome. The steroid profile associated with Cushing's syndrome caused by adrenal adenoma was quite distinct from that associated with the syndrome caused by adrenal hyperplasia. Serum concentrations of androstenedione, dehydroepiandrosterone, estrone, estradiol, 17 hydroxyprogesterone, pregnenolone, and testosterone were significantly higher in patients with adrenal hyperplasia than in those with an adenoma. We compared the results of this HPLC/RIA method with those of 125I RIAs. The use of a HPLC/RIA system to obtain an accurate and sensitive profile of a range of serum steroids, as described here, obviates the need for large volumes of blood. PMID- 1868593 TI - Predictive, error-compensating kinetic method for enzymatic quantification of creatinine in serum. AB - Here we describe an error-compensating kinetic-based method for the enzymatic quantification of creatinine in serum. The method, which has a large linear range and very low dependency on experimental variables that influence enzyme activity, is based on the use of creatinine amidohydrolase in a four-step coupled reaction sequence to generate a product that is monitored photometrically. We collected data for absorbance vs time during two to four half-lives of each reaction and fit a first-order model to the data to compute the total absorbance change that would be measured if the reaction were monitored to completion. Computed values of absorbance change agreed well with measured values and varied linearly with creatinine concentration in the sample throughout the range examined: 44 to 1326 mumol/L. A twofold change in enzyme activity in the final reaction mixture (3.3 to 6.6 kU/L) produced changes of only 12% and 4% for creatinine concentrations of 44 and 353 mumol/L, respectively. Results (y) for 39 serum samples that contained creatinine concentrations between 20 and 1800 mumol/L agreed well with liquid chromatographic results (x), yielding linear least-squares statistics of y = (1.03 +/- 0.01) x + (5 +/- 5) mumol/L (r = 0.995, Sy.x = 37 mumol/L). We conclude that the predictive kinetic approach is a robust method for the quantification of creatinine in serum. PMID- 1868594 TI - Characterization of sodium-selective optode membranes based on neutral ionophores and assay of sodium in plasma. AB - Plasticized poly(vinyl chloride) membranes that incorporate a highly lipophilic sodium-selective neutral ionophore (ETH 4120) and novel H(+)-selective chromo ionophores, lipophilic isologs of Nile Blue, are used in the competitive binding of Na+ and H+ for a reversible, optical determination of sodium activities in buffered solutions at different selected pH values. These optode membranes are used to assay total sodium concentrations in pH-buffered human blood plasma. PMID- 1868595 TI - Carboxyterminal propeptide of type I procollagen in cerebrospinal fluid in childhood and in children with leukemia undergoing intrathecal treatment. AB - We determined the reference interval for the carboxyterminal propeptide of type I procollagen (PICP), an indicator of the synthesis of type I collagen, in cerebrospinal fluid (CSF) by studying 32 infants and children, ages less than or equal to 15 years. The concentration of PICP is age dependent, with particularly high concentrations occurring in children younger than 1.5 years. In older children the concentration is stable (reference interval 20-92 micrograms/L). We also investigated the possibility that PICP in CSF could reflect local fibroproliferative changes in the arachnoid in a cohort of 42 children with acute lymphoblastic leukemia who were monitored by repeated sampling in connection with intrathecal therapy. Initially, there was no difference in PICP between the children with newly diagnosed leukemia and the controls. PICP concentrations were significantly higher (P less than 0.01) during intrathecal methotrexate therapy, with median values above the reference interval. Continuous corticosteroid treatment was associated with a significant decrease in PICP (P less than 0.02 and P less than 0.01, respectively, in two groups treated according to different protocols), close to the lower limit of the reference interval. Intrathecally administered methotrexate and systemic corticosteroid treatment are known to be associated with the development of arachnoiditis and with general repression of collagen synthesis, respectively. We conclude that PICP in CSF is a sensitive indicator of local fibroproliferation and ongoing collagen synthesis. PMID- 1868596 TI - Measurement of the ratio of lecithin to sphingomyelin in amniotic fluid by fast atom bombardment mass spectrometry. AB - We describe a fast atom bombardment mass spectrometric method to determine the ratio of lecithin to sphingomyelin in amniotic fluid. Between m/z 400 and 1000, amniotic fluid extracts showed clear peaks for only sphingomyelin and lecithin. The molecular species of fatty acid in the phospholipids were analyzed quantitatively and quickly in a small volume of the extracts. The dipalmitoyllecithin/palmitoylsphingomelin ratio, determined by the proposed method, showed a reasonable correlation to the lecithin/sphingomyelin ratio measured by thin-layer chromatography. This method allows rapid and sensitive measurement of these phospholipids. PMID- 1868597 TI - Analysis of ion behavior and potentials in a Na+ ion-selective membrane containing methyl monensin. AB - Ion-selective electrodes (ISEs) are widely used in clinical examinations. The mechanisms of ISEs have been studied to develop a disposable ISE for "dry chemistry" analyses. The behavior of Na+ and Ag+ in an ion-selective polymer liquid membrane (ISM) containing methyl monensin (MMO), which is selective for Na+, has been clarified by x-ray microanalysis and measurement of electrical potential. The results indicate that Na+ is not transported across the membrane because of a stability of the Na(+)-MMO complex, whereas Ag+ (from the Ag/AgCl electrode) is transported with Cl- across the membrane by diffusion. The difference in potential, which follows a Nernst gradient, is generated by the formation of a double layer of electrons at the interface between the ISM and the electrolyte solution. These results are explainable by the stability of the trap in the polymer liquid membrane. MMO acts as a stable trap of Na+ and as a metastable site of Ag+ for movement. PMID- 1868598 TI - Cancer antigen 125 in serum and ascitic fluid of patients with liver diseases. AB - Serum concentrations of cancer antigen 125 (CA 125) were determined for 373 patients with various liver diseases: 57 with acute hepatitis, 57 with chronic hepatitis, 244 with liver cirrhosis (86 compensated and 158 decompensated), and 15 with primary liver cancer. The antigen was measured simultaneously in the serum and ascitic fluid of 46 of the patients with liver cirrhosis and sequentially in the serum and ascitic fluid of another 25 cirrhotics treated with paracentesis and (or) diuretics. Abnormal results for CA 125 were detected in sera from 4% of the patients with acute or chronic hepatitis, 60% of the patients with liver cirrhosis, and 67% of the patients with primary liver cancer. The main factor associated with abnormal serum concentrations of this antigen was the presence of ascites, with pathological CA 125 values in 94% of patients with ascites without jaundice (mean 566 +/- 528 arb. units/mL), compared with only 40% of patients with jaundice and without ascites (mean 40.1 +/- 28.5 arb. units/mL) (P less than 0.001). High concentrations of CA 125 were mainly associated with spontaneous bacterial peritonitis. The serum concentration of CA 125 decreased after treatment with paracentesis, but increased in patients treated with diuretics rather than paracentesis. The release of this antigen in liver cirrhosis appears to be independent of the liver disorder and, rather, results from peritoneal synthesis of this antigen. PMID- 1868599 TI - Role of the clinical laboratory in evaluation of argininosuccinate lyase deficiency. PMID- 1868600 TI - Influence of intermediate-density lipoproteins on the accuracy of the Friedewald formula. AB - Values of low-density lipoprotein (LDL) cholesterol (C) according to the Friedewald formula (Clin Chem 1972;18:499-502) were compared with those obtained by lipoprotein fractionation in 98 healthy subjects (control group), 135 specimens from patients with peripheral vascular and cerebrovascular disease (atherosclerotic group), and 45 with chronic renal failure on hemodialysis (CRF group). All had concentrations of total cholesterol between 3.23 and 7.76 mmol/L (1.25-3.00 g/L) and triglycerides less than 3.39 mmol/L (less than 3.00 g/L). The percentage error of calculated LDL-C was 4% in controls with a cholesterol/triglycerides (C/TG) ratio for very-low-density lipoprotein (VLDL) of 0.20, but greater than 60% in those with a (C/TG)VLDL ratio of 0.40. The percentage of error in sera of patients with atherosclerosis and chronic renal failure was higher than in controls with a similar mean (C/TG)VLDL ratio. The percentage of error of calculated LDL-C increases progressively with the increase in the C/TG intermediate-density lipoprotein (IDL) ratio, both in controls and in the atherosclerotic and CRF groups. Similar findings are observed when the mean percentage of error of measured LDL-C is evaluated. The percentage of error from calculated LDL-C in the atherosclerotic and CRF groups is significantly lower than that obtained by comparison of LDL-C separated by ultracentrifugation when the "broad cut" LDL (IDL plus LDL, both by ultracentrifugation) was used. The high percentage of errors found in the groups of patients studied underlines the need for caution when assessing the reliability of the Friedewald formula, particularly in cases in which disturbances in IDL composition are suspected. PMID- 1868601 TI - Interference in thyroid-function tests in postpartum thyroiditis. AB - Three women are described from a study of patients with postpartum thyroiditis whose sera gave spuriously increased concentrations of free thyroid hormone because of antibody binding of radiolabeled thyroxin (T4) and triiodothyronine (T3) analogs. All of the women showed increased serum concentrations of thyroid autoantibodies. The antibody binding of radiolabeled analogs and its effect on free T4 and free T3 assays disappeared by 48 weeks postpartum. Postpartum women who develop thyroid autoantibodies have approximately 2% prevalence of increased binding of radiolabeled analogs, which can result in an interference in thyroid hormone assays involving T4 and T3 analogs. PMID- 1868602 TI - S-troponin T in suspected ischemic myocardial injury compared with mass and catalytic concentrations of S-creatine kinase isoenzyme MB. AB - In a multicenter study we compared three tests for ischemic myocardial injury (IMI): a new, automated enzyme immunoassay for S-troponin T (S-TNT; Boehringer Mannheim) and two S-creatine kinase (CK) isoenzyme MB assays (mass and catalytic concentrations). For critical evaluation of clinical sensitivity, we studied 243 cases with an IMI prevalence of 43% and an 18% prevalence of cases with unstable angina. Relative peak values of S-TNT and S-CK-MB (mass) after onset of pain were four- to fivefold higher than S-CK-MB (catalytic) results. Increases of S-TNT and S-CK-MB (mass), even though still within their reference ranges, indicated minor myocardial damage in about one-third of the cases primarily classified as unstable angina. The diagnostic window for S-TNT ranged from hours to weeks after the acute episode. The time courses were frequently biphasic, with the initial S TNT peak closely paralleling that of the mass concentrations of S-CK-MB. With a biological half-life for S-TNT of 2 h, the prolonged increases in S-TNT indicate a continuous release of S-TNT from necrotizing cells. Clinical specificities of S TNT and S-CK-MB (mass) were greater than that of S-CK-MB (catalytic), even in the presence of 30% to 40% severe skeletal muscle injuries. The combination of S-TNT and S-CK-MB (mass) is excellent for detection of acute IMI, including minor myocardial damage. PMID- 1868603 TI - Time-resolved immunofluorometric assay of 17 beta-hydroxysteroid dehydrogenase in plasma. AB - We describe a time-resolved immunofluorometric assay (TR-IFMA) for human 17 beta hydroxysteroid dehydrogenase (17HSD) in which antibody-coated microtiter strip wells and europium chelate-labeled polyclonal antibodies are used. In preparing the label, a polyclonal antibody is affinity-purified and derivatized with diethylenetriamine-pentaacetic acid. With this derivative, five to eight europium ions can be combined with one antibody molecule without decreasing the antibody's immunoreactivity. The minimum detectable concentration of 17HSD is 0.13 microgram/L; the intra- and interassay CVs are less than 8% and less than 15%, respectively, for concentrations between 0.3 and 100 micrograms/L. There is no difference between the concentrations of 17HSD in plasma specimens taken during the proliferative and luteal phases of the menstrual cycle, the measured mean concentration being 0.22 microgram/L. We found no correlation between plasma 17HSD and progesterone concentrations. The plasma concentrations of 17HSD increase during pregnancy, the mean concentrations being 1.5, 4.4, and 12.5 micrograms/L, during the first, second, and third trimesters of pregnancy, respectively. In the specimens from 18 men, the mean concentration was 0.18 microgram/L. In six plasma specimens from patients with endometrial adenocarcinoma, the mean concentration was 0.20 micrograms/L. Pre-analytical aspects are important in the assay of 17HSD because of the lability of the enzyme protein. Preferably, blood should be sampled into EDTA-containing tubes, plasma should be separated within 15 min, and glycerol must be added without delay to a final volume of 200 mL/L. PMID- 1868604 TI - Computerized approach to monitoring aminoglycosides. AB - Aminoglycosides are still used extensively in the treatment of nosocomial infections with Gram-negative bacteria. However, the treatment is associated with several adverse effects. Aminoglycosides monitoring is therefore essential to prevent toxic accumulations and to reach therapeutic concentrations. A computer program, PHARMONITOR, has been developed to optimize aminoglycosides monitoring, responding to the demands of most clinical daily situations. This program, based on a one-compartment open pharmacokinetics model, is developed for IBM PC compatible computers, using D-Base III+. It can calculate t1/2, Vd, Cldrug, Cpmax, and the theoretical optimal dose and interval and also evaluates the creatinine clearance. The program has been conceived to allow maximal speed, flexibility, and reliability by the use of (e.g.) a linear least-squares analysis, the possible reference to previous protocols, the extensive use of keywords to classify and recall patients according to their pathologies, the development of messages recommending maximal dose or minimal dosing interval, and increasing the safety of the analysis. We consider the program a valuable tool for adjusting aminoglycoside dosage in individuals. PMID- 1868606 TI - Prevalence of familial dysalbuminemic hyperthyroxinemia in serum samples received for thyroid testing. AB - The prevalence of familial dysalbuminemic hyperthyroxinemia (FDH), a condition sometimes mistaken for hyperthyroidism, has not been clearly established. I present a study of the prevalence of FDH in serum samples received for thyroid function tests in a reference laboratory. A prospective study of 15,674 serum samples was carried out over 24 months, of which 13,232 cases were from women (84.42%) and 2442 were from men (15.58%). FDH was diagnosed in 26 cases, 22 in women and four in men. Therefore, the prevalence of FDH in the total number of samples from both sexes was 0.17%, 0.17% in women, and 0.16% in men, which is consistent with a dominant autosomal type of familial transmission. These findings demonstrate that cases of FDH occur frequently; therefore, every laboratory must be prepared to recognize them and thus avoid an incorrect diagnosis of the patient's thyroid function. PMID- 1868605 TI - Free and bound malondialdehyde measured as thiobarbituric acid adduct by HPLC in serum and plasma. AB - Assay of free and total malondialdehyde (MDA) in human serum and plasma from healthy subjects and from patients with high risk of lipoperoxidation was performed as follows: (a) acidic (HClO4, pH 1, at 20 degrees C) or basic (NaOH, pH 13, at 60 degrees C) treatments for 30 min; (b) reaction of the protein-free extract (obtained by acid precipitation) with thiobarbituric acid (TBA); (c) HPLC separation on C18 columns with an eluting solution of methanol/phosphate buffer, 10 mmol/L, pH 5.8 (40/60, by vol), at a flow rate of 1.5 mL/min. Free MDA averaged 0.042 (SEM 0.008) and 0.043 (SEM 0.007) mumol/L, respectively, in serum and plasma from healthy subjects. Free (+/- SEM) MDA increased significantly in the plasma from cancer patients (0.270 +/- 0.047 mumol/L) and from hemodialyzed patients (0.214 +/- 0.035 mumol/L). In serum of hemodialyzed patients, analyses for total MDA were unsuitable because of interfering peaks. MDA bound to NH2 groups constituted 83.2% and 83.5% of total MDA in serum and plasma of healthy subjects, respectively, and only 58% in plasma of hemodialyzed patients. PMID- 1868607 TI - What can be achieved in an external quality-assessment scheme with a small number of participants: four years of experience with thyroid-related tests in Israel. AB - The Israel External Quality-Assessment scheme (EQAS) provided service from 1985 to 1989, primarily to laboratories in Israel. Participation was voluntary and confidential, and involved 30-35 laboratories performing thyroid-related function tests. Scheme design included 36 human serum specimens distributed to the participants at the beginning of each year. For 12 months, three specimens were analyzed each month and the results were reported to EQAS on pre-agreed dates. Monthly reports sent by EQAS to participants after analysis of the results included the overall consensus mean used as target value, between-laboratory agreement, individual laboratory bias, and recovery data. The overall consensus mean calculated as all-laboratory trimmed mean was validated by reproducibility and recovery studies. Samples with undetectable concentrations of thyrotropin (TSH), obtained from patients proven thyrotoxic, were used to validate measurement of very low TSH concentrations. During the scheme, liquid serum was found superior to lyophilized specimens for distribution to the participants. The scheme helped stimulate major improvements in between-laboratory agreement, especially for low TSH concentrations, with CVs decreasing from 180% in the first year to 20% in the fourth year. Each laboratory's performance also improved as judged by the median bias and variability of bias and by the considerable decrease in the number of laboratories with unacceptable performance for all tests. Method-related differences in performance were observed despite the small number of participants. Better methods, e.g., a radioimmunometric method for TSH, were detected and adopted by the participants, with concomitant improvement in performance. Transfer to analog procedures for free thyroxin, in addition to, but mostly instead of, thyroxin, was also documented, with no gain in analytical performance. Despite this being a small scheme, most of the goals achievable with a large scheme were realized. PMID- 1868608 TI - Simple, sensitive measurement of carbon monoxide in plasma. AB - A simple, sensitive method for estimating carbon monoxide in plasma is described. In this method, the carbon monoxide in plasma is trapped with hemoglobin and subsequently estimated by dithionite reduction. The method has an intra- and interassay precision (CV) of 10.7% and 12.8%, respectively, at a concentration of 1.12 mg of carbon monoxide per liter and has a detection limit of 0.1 mg/L. The reference interval for carbon monoxide in plasma from 17 men and eight women ranged from 0.14 to 0.60 mg/L (mean 0.36 mg/L). PMID- 1868610 TI - Benign inherited hyperphosphatasemia of intestinal origin: report of two cases and a brief review of the literature. AB - Two families with benign hyperphosphatasemia of intestinal origin were studied and compared with six other cases reported in the literature. No evidence of clinical abnormalities or explanations for the unusual enzyme concentrations were found. Agarose gel electrophoresis of alkaline phosphatase (ALP, EC 3.1.3.1) isoenzymes in serum demonstrated markedly increased intestinal isoforms (the "soluble" and the "hydrophobic" forms), which accounted for approximately 60% of total ALP activity. The description of these families demonstrated patterns suggesting autosomal-dominant inheritance, even if the precise genetic background of the abnormality affecting the enzyme production or the control mechanisms for its entry into the circulation could not be determined. Exact recognition of this benign biochemical abnormality should help to avoid unnecessary investigation. PMID- 1868609 TI - Above-normal urinary excretion of retinol-binding protein and albumin in Albustix negative hypertensive patients. PMID- 1868611 TI - 2,3-Butanediol in plasma from an alcoholic mistakenly identified as ethylene glycol by gas-chromatographic analysis. AB - 2,3-Butanediol was mistakenly identified as ethylene glycol in plasma specimens from two alcoholic patients. The cyclic phenylboronate ester derivatives of 2,3 butanediol and ethylene glycol had the same retention time when OV-17 was used as the stationary phase for gas chromatography. This led to incorrect diagnosis of ethylene glycol poisoning and unnecessary invasive therapy. Plasma from two chronic alcoholics contained 2,3-butanediol at 3.5 and 3.4 mmol/L. The elimination half-life of 2,3-butanediol was 3.9 days when ethanol was administered during therapy for suspected ethylene glycol poisoning. Low concentrations of 2,3-butanediol might be present in blood of chronic alcoholics as a result of a novel pathway of intermediary metabolism associated with some forms of alcoholism. However, a more likely explanation for fairly high concentrations of 2,3-butanediol is enzymatic production from 2-butanone. This ketone occurs in denatured alcohol preparations often consumed by alcoholics in Sweden. PMID- 1868612 TI - Detection of two abnormal hemoglobins, Hb Manitoba and Hb G-Coushatta, during analysis of glycohemoglobin (A1c) by high-performance liquid chromatography. AB - This report concerns the detection of two abnormal hemoglobins (Hb), Hb Manitoba and Hb G Coushatta, during analysis for glycohemoglobin (Hb A1c). Blood samples from two diabetic patients, analyzed for Hb A1c by HPLC, were found to contain additional Hb peaks. The presence of an abnormal Hb was confirmed in both instances by hemoglobinopathy studies. Structural studies determined the two Hb variants to be Hb Manitoba (alpha 2 102 Ser----Arg beta 2) and Hb G-Coushatta (alpha 2 beta 2 22 Glu----Ala). The significance of the presence of an abnormal Hb in Hb A1c analysis is discussed. PMID- 1868613 TI - Assay interference caused by powder from prepowdered latex gloves. PMID- 1868614 TI - More on interference of bilirubin in creatinine determination by Hitachi analyzers. PMID- 1868615 TI - Interdependence of non-sex-hormone-binding globulin-bound testosterone and cortisol. PMID- 1868616 TI - Influence of the enzymatic kinetic model on selection of reaction conditions for extending the linear range of kinetic methods. PMID- 1868617 TI - Use of chemical denaturation for centrifugal analyzer determination of lactate dehydrogenase 1. PMID- 1868618 TI - Pitfalls in measuring choriogonadotropin and its free subunits in decomplemented sera. PMID- 1868619 TI - Effect of polypropylene centrifuge tubes on extraction of desipramine from blood. PMID- 1868620 TI - Oxygen radicals: their role in selected gastrointestinal disorders. AB - In this article, the evidence for the involvement of free radicals in some of the gastrointestinal disorders is reviewed. Oxygen radicals are partially reduced oxygen species that include superoxide, and hydroxyl radicals, and hypophthalous acids. Most cells possess numerous antioxidant enzymes and scavengers to protect themselves from these injurious agents; the rate of production of reactive oxygen metabolites may exceed the capacity of the antioxidant defenses thus resulting in tissue damage. The gastrointestinal tract is particularly well endowed with the enzymatic machinery necessary to form large amounts of oxygen radicals. Sources of radicals in the gastrointestinal tract include mucosal xanthine oxidase and NADPH oxidase found in the resident phagocytotic leukocytes (macrophages, neutrophils, eosinophils) of the lamina propria. Other sources of oxygen radicals in the gastrointestinal tract involve ischemia and reperfusion, drug ingestion, diet and radiation therapy. Recent studies have demonstrated the involvement of oxygen radicals following active episodes of small-intestinal ischemia, ulcerative colitis, pancreatitis and gastric ulcer. In contrast to cell antioxidants, control of tissue free radical levels is now pharmacologically feasible and perhaps justified for specific diseases. However, carefully designed and controlled clinical trials are needed. PMID- 1868621 TI - Advances in the comprehension of the pathophysiology of bile secretion. PMID- 1868622 TI - APACHE II scoring in surgical upper gastrointestinal emergencies. PMID- 1868623 TI - Severe acute pancreatitis: newer insights in diagnosis and management. PMID- 1868624 TI - Kinase activity and genetic characterization of a growth related antigen of Drosophila. AB - The Drosophila developmental antigen recognized by the monoclonal antibody F7D6 is expressed in dividing embryonic and imaginal cells but is lost from all differentiating tissues except electrogenic cells of the nervous system and spontaneously contracting muscles. The 63 kDa antigen is associated with the inner surface of plasma membranes and is expressed in several classes of tumorous mutants of Drosophila. The monoclonal antibody was used for immunoprecipitating the antigen for biochemical characterization and for screening expression vector cDNA libraries. Here we report that this oncodevelopmental antigen is a phosphoprotein and a serine-threonine specific protein kinase. A 1.6 kb cDNA isolated by immunological screening of an ovarian library hybridized to a single band on polytene chromosomes, localizing the gene to 72F on the left arm of the third chromosome. Immunofluorescence assays of deficiency stocks in the region confirmed the location of the gene and identity of the cDNA clone, and mapped the gene between the left breakpoints of Df(3L) st100.62 and Df(3L) stj7, i.e., between 72F3-7 and 73A1-2. The biochemical and genetic properties indicate that this is a novel growth-related kinase of Drosophila. PMID- 1868625 TI - Regulatory elements near the Drosophila hsp 22 gene required for ecdysterone and heat shock induction. AB - A transient expression assay was used to localize cis-acting DNA regulatory elements near the Drosophila heat shock protein (hsp) 22 gene, that are involved in heat shock expression and in ecdysterone-induced expression. The results identify a region between positions -320 and -232 that is essential for ecdysterone control, but not for heat-induced expression, and a sequence between 199 and -156, which, when deleted, leads to the loss of heat shock induction. To investigate the function of these DNA sequences, transfection-competition experiments were carried out. The evidence suggests that the DNA regulatory sequences identified by transient expression studies contain binding sites for transacting transcription factors. PMID- 1868626 TI - Facilitation by partial hepatectomy of tumor growth within the rat liver following intraportal injection of syngeneic tumor cells. AB - The effects of both mechanical trauma and regeneration on the growth of intraportally injected tumor in the rat liver were investigated using two-thirds partial hepatectomy (PH). Tumor grew at the excision scar when PH was performed less than 2 days before tumor injection (34/34 animals). However, when the PH was performed 4-7 days before injection, tumor developed within the regenerating lobe, but not at the scar (50/51). Injecting the same cell dose into rats with intact livers caused few tumors to develop in 12/30 animals. Intraportally injected 51Cr-labelled tumor cells distributed uniformly in the liver irrespective of the time after PH. Patterns of tumor take seen at different times after PH were not due to selective trapping of the injected cells. Liver extracts showed that epidermal growth factor-like activity was unaltered by PH, while heparin-binding growth factor activity peaked at 2 days post-PH, before the incidence of tumor growth in the parenchyma increased. We observed two peaks of DNA synthesis at days 1 and 4 post-PH by pulse labeling with [125I]deoxyuridine and bromodeoxyuridine. Bromodeoxyuridine immunohistochemistry showed the first peak to be confined to hepatocytes. The second peak involved non-hepatocytes and coincided with the beginning of enhanced tumor take in the regenerating lobe. PMID- 1868627 TI - Colonization characteristics of a murine mammary tumor cell line that metastasizes frequently to the heart. AB - Metastasis by mouse mammary tumor cells is usually confined to lung. This paper describes the metastatic behavior of an established mouse mammary tumor cell line, 4526, that in addition to lung and liver metastasis, shows a high rate of heart metastases. The tumor cells were inoculated into the fourth mammary fat pad of syngeneic mice and their pattern of distant colonization was analysed qualitatively as well as quantitatively. We found that the cell line produced 100, 70 and 40% metastases to the lung, liver and heart, respectively. While the lung metastases appeared primarily as nodular masses, the liver metastases occurred both as nodular and diffuse masses. In addition, we observed that the metastatic load of each of the different lung lobes of individual mice was proportional directly to its relative size, and there seemed to be an inverse relationship between the occurrence of lung and liver metastases in individual mice. As compared to lung and liver metastases, heart metastases were found to be localized internally, usually in the cavity and wall of the ventricle. Furthermore, hearts with metastases revealed destruction of cardiac tissue and blockage of the cavity space. Our results show that 4526 cells are phenotypically stable, since the metastatic behavior of several clonal derivatives of the cell line obtained from lung, liver and heart colonies were found to be identical to that of the parental cell line. Thus this cell line, because of its unparalleled metastatic characteristics, offers a model for investigations into the biology of mammary tumor cell metastasis, especially heart metastasis. PMID- 1868628 TI - Development of lymph node and pulmonary metastases after local irradiation and hyperthermia of footpad melanomas. AB - C57BL/6 mice with syngeneic B16-F10 melanomas were treated 7 days after tumor inoculation into the footpad with local hyperthermia (HT) of 43.5 degrees C for 90 min. A combination of local 30 Gy X-irradiation (XRT) given 2, 4 or 12 h after HT cured the primary tumor in 34/35 mice, with irreversible damage to normal foot tissues in most of the animals. When 7.5, 10 or 15 Gy XRT were delivered 4, 18 or 24 h after HT, there were only a small number of cures and also a much smaller incidence of irreversible normal tissue damage. HT alone resulted in a significant (P less than 0.001) increase in metastases to regional lymph nodes (RLN) and the lungs. The 'curative' doses of combined XRT and HT resulted in a significant (P less than 0.001) decrease in metastasis to RLN and to the lungs. Conversely, subcurative doses of combined therapy resulted in an increase in RLN and lung metastasis (P less than 0.001). Abdominal lymph node metastasis, not usually seen in control mice, is markedly increased after HT alone or in combination with subcurative XRT (P less than 0.001). The overall survival of mice treated with HT alone is decreased (P less than 0.0028). The survival of mice treated with HT followed 4, 18 or 24 h later with 10 Gy XRT is further decreased (P less than 0.0025). These data show that subcurative HT, or XRT plus HT, increases the incidence of spontaneous metastasis in this syngeneic mouse melanoma model. Curative doses prevent this effect on metastasis, but there is an unacceptable incidence of irreversible damage to the tumor-bearing foot. The cause(s) of this phenomenon are not known. PMID- 1868629 TI - Drug sensitivity and metastatic ability in B16 melanoma cells. AB - We have previously reported that highly metastatic cell lines derived from KHT fibrosarcoma (KHT 35L1) and B16 melanoma (B16F10) are more resistant to N phosphonacetyl-L-aspartate (PALA) and methotrexate (MTX) than the parental cell lines. This correlation between drug resistance and metastatic ability suggested the possibility that both phenotypes might have arisen in parallel as a result of a similar mechanism. In this study, we examined this possibility by reproducing the selection procedure for B16F10 cells (by serial passage of B16F1 cells as lung nodules) and testing the cells at each passage for changes in resistance to PALA and MTX. The results confirm that serial passage of B16F1 cells as lung nodules (LP) selects for cells with increasing metastatic ability (100-fold after seven passages), but these cells did not develop increased resistance to PALA and became more sensitive to MTX. For comparison B16F1 cells were also serially passaged (six passages) as leg tumors (LT). These cells became slightly more metastatic (3-fold) than B16F1 cells maintained in tissue culture, and demonstrated a small increase in sensitivity to MTX, as in the LP lines. There was also an apparent increase in resistance to PALA. In no instance was there a parallel increase in drug resistance and metastatic ability indicating that these two phenotypes do not necessarily arise in parallel in this cell line. PMID- 1868630 TI - Resistance of the embryonic notochord to invasion by malignant neurogenic tumor cells in vitro. AB - Very few tissues in vivo are resistant to invasion by malignant cells. In this paper, confrontation cultures consisting of chick embryonic notochord fragments and cell aggregates from three malignant neurogenic cell lines showed a resistance of the embryonic organ to malignant invasion by tumor cells. The mechanism of resistance remains unclear. PMID- 1868631 TI - Attachment and invasion of high- and low-metastatic clones of RCT sarcoma in a three-dimensional culture system. AB - High- and low-metastatic clones established from poorly differentiated murine sarcoma (RCT sarcoma) spontaneously developed in C3H/He mice were used in this study. Attachment and invasion, which are factors likely related to metastatic ability, of these clones were investigated in a three-dimensional culture system using embryonic chick heart fragments and tumor cell aggregates. The effects of Nocodazole, which interferes with the function of microtubules, and cytochalasin B, which affects the actin assembly in cytoplasmic extensions, on these factors were also examined. Metastatic ability was correlated with attachment and invasiveness of RCT sarcoma. Invasiveness of tumor cells was suppressed by the addition of Nocodazole to the culture medium. Since the disappearance of cell polarity, resulting from the inhibition of tubulin assembly, was found to coincide with the suppression of invasion, directional migration is considered to be involved in the invasion of tumor cells. Cytochalasin B caused a marked decrease in the ratio of attachment of tumor aggregates to embryonic chick heart fragments. The increased ability of invasion and attachment of RCT(+) cells compared with RCT(-) cells seems to contribute to their propensity to metastasize. PMID- 1868632 TI - Fetal drug therapy: principles and issues. AB - The 1990s may revolutionize the care of the fetus and create new options in gene control, immunotherapy, and drug therapy not only to identify susceptible populations but to treat selectively that population without increasing the risk to the mother. Fetal therapy is a notable goal, even now somewhat within our grasp. No longer is the womb an isolated, forbidding environment, but it is accessible with such tools as magnetic resonance imaging, ultrasonography, CVS, Doppler, and sound clinical judgement. Current limitations in our understanding of the pharmacokinetics associated with these chemical temper our enthusiasm. The development of biomarkers for appropriate fetal drug therapy is to be encouraged, but also the development of fetal and maternal biomarkers that will assist the physician in actively avoiding inappropriate fetal drug therapy is necessary, whether dose or chemical dependent. PMID- 1868633 TI - Low-dose aspirin to improve perinatal outcome. AB - The list of clinical conditions for which aspirin may produce abatement or reversal of pathologic processes continues to be expanded. There are, however, definite risks reported from the use of aspirin during pregnancy, even though some of the findings have been contradictory. Some of the potential adverse effects on the infant also remain unclear. Potential benefits from the use of low doses of aspirin during pregnancy (although promising) are still experimental. Large clinical trials in the United States and overseas are currently assessing the effectiveness of low-dose aspirin in preventing preeclampsia and fetal growth retardation. A review of the world's literature to date describes over 300 pregnancies in which low-dose aspirin has been used with no evidence of major adverse effects. Until more conclusive evidence emerges, however, caution against the indiscriminate use of aspirin in any dose during pregnancy is urged. Clinicians who decide to manage complicated or potentially complicated patients with chronic administration of aspirin must continue to study these mothers, fetuses, and neonates intensively and to document their results. Because of the fear of teratogenic effects in the first trimester, initiation of aspirin therapy should be withheld until the 13th week of gestation. However, current data indicates it can be continued until delivery without complication. Monitoring of these patients should include: warning signs and symptoms of bleeding, serial ultrasonography for fetal growth and fluid, serial fetal echocardiography, and neonatal evaluation for bleeding complications. Such clinical experience will add immensely to our understanding of the safety and efficacy of aspirin during pregnancy. PMID- 1868634 TI - Calcium, magnesium, and zinc supplementation and perinatal outcome. AB - The overall importance of nutrition to favorable perinatal outcome is only beginning to be fully appreciated. Although nutritional status can be linked to such things as socioeconomic class and education, it is nutrition directly that exerts a biologic effect. This review has attempted to look at three elements and their relationship to maternal and fetal outcome. At the present time, there does not seem to be a role for routine magnesium supplementation during pregnancy. Magnesium deficiency, as an isolated nutritional deficiency, is rare, and the evidence is, at best, weak that magnesium supplementation reduces the risk of poor perinatal outcome. Zinc deficiency is also a very rare isolated nutritional finding. Our ability to measure zinc accurately, be it in leukocytes or serum, is improving, but the routine use of zinc supplements during pregnancy cannot be recommended at this time. It may be that zinc will be a useful diagnostic marker, rather than a therapeutic intervention. There is substantial evidence that the average American diet does not contain sufficient calcium. An expansive literature continues to grow in the areas of calcium and colon cancer, calcium and breast cancer, calcium and hypertension, and calcium and osteoporosis. Is it possible that our susceptibilities to these problems begin in utero? Obviously, the answer is unknown. What is known is that supplemental calcium to some degree is needed in the diets of most Americans and in about two thirds of pregnant women. Calcium supplementation seems to affect blood pressure favorably and, pending confirmation with larger trials, may significantly reduce prematurity and preeclampsia risk, thus improving perinatal outcome for a large number of our high-risk patients. PMID- 1868635 TI - In utero treatment of fetal metabolic disorders. PMID- 1868636 TI - Maternal insulin to lower the risk of fetal macrosomia in diabetic pregnancy. AB - Fetal macrosomia is a well-recognized adverse outcome associated with gestational diabetes. Weekly measurement of fasting and postprandial glucose should identify those with fasting (greater than or equal to 100 or 105 mg/dl) or postprandial (greater than or equal to 120 mg/dl 2 hours after a meal) hyperglycemia who are at increased risk for perinatal mortality. If the prevention of macrosomia is desired, the use of prophylactic insulin, initiated as early as possible, but at the latest before 36 weeks' gestation, without regard to glycemia is effective. Alternatively, glucose self-monitoring (four to six times daily with institution of insulin treatment when fasting glucose exceeds some arbitrary threshold such as 90 mg/dl or postprandial values exceed a threshold such as 100 mg/dl) is likely to be equally effective with fewer patients requiring insulin injections. PMID- 1868637 TI - Pharmacologic therapy for fetal arrhythmias. AB - Although great strides have been made in diagnosing fetal cardiac anatomic and functional abnormalities, in utero cardiac therapy is limited to the treatment of significant arrhythmias. The fetal prognosis may change if the dysrhythmia persists or if the condition results in intrauterine heart failure. When either complication is evident, intrauterine drug therapy may be indicated if the fetus is considered too immature for delivery. Information from case reports has shown several drugs to be useful to cardiovert the fetus, with digitalis being the pharmacologic agent used most often. At present, treatment consists mainly of transplacental administration of antiarrhythmic agents with the object of normalizing FHR and rhythm and abolishing, or preventing, fetal cardiac failure. Various agents have been used with variable success. More direct fetal therapy by intramuscular injection or umbilical vein infusion may replace unsuccessful indirect maternal therapy. It is unclear why some fetuses respond (or appear to respond) and others have hydrops and die in the absence of congenital heart disease or documented infection. With proper therapy, many fetuses survive and have a satisfactory prognosis, depending on the form of arrhythmia and the nature of any cardiac structural defects. PMID- 1868638 TI - Indomethacin therapy in the treatment of symptomatic polyhydramnios. AB - It appears that maternal indomethacin therapy may be a useful adjunct in selected cases of polyhydramnios. Initial evaluation should include glucose tolerance testing and a thorough search for fetal abnormalities by ultrasonography. In the patient with symptoms such as premature labor or respiratory compromise, an initial amniocentesis should be considered for decompression and fetal karotype. Oral indomethacin therapy can then be started. Although the optimal dose is unknown, a 25-mg oral dose every 6 hours appears adequate. Ultrasound assessment of amniotic fluid volume should be done once or twice weekly. If oligohydramnios develops, the indomethacin should be discontinued, and the amniotic fluid volume serially monitored. Fetal echocardiography should be considered in the first 24 hours after therapy has been initiated and weekly thereafter. Evidence of severe constriction of the ductus arteriosus or tricuspid regurgitation warrants discontinuation of the indomethacin; lesser degrees of ductal constriction can be treated by decreasing the dose of the medication. PMID- 1868640 TI - Antenatal therapy to minimize neonatal intraventricular hemorrhage. AB - Periventricular-intraventricular hemorrhage is an important problem, resulting in significant mortality and morbidity. Attempts to reduce this complication require an understanding of its pathogenesis. In this chapter a model was proposed, consisting of a series of events resulting in rapid changes of cerebral blood flow and intracranial pressure and leading to rupture of the unique fragile vessels of the germinal matrix and intraventricular regions. Understanding the beneficial physiologic changes induced by such agents such as phenobarbital and vitamin K and that such pharmacologic therapy must be started during the antenatal period has resulted in significant reductions of severe grades of IVH. Further prospective studies are needed to confirm these results using these two drugs alone and in combination. Other potentially beneficial drugs such as indomethacin should be investigated. Although the benefits of such therapy may improve perinatal outcome, the emphasis in our discipline should be the continued attempt to prevent the delivery of these VLBW infants. PMID- 1868639 TI - Pharmacologic induction of fetal lung maturity. AB - The consequences of a preterm birth are usually not secondary to a developmental abnormality but rather due to the immaturity of one or more organ systems. Because neonatal RDS is the most common and the most severe complication of a preterm delivery, a major emphasis has been placed on its prevention and/or treatment. Despite intensive research efforts directed at preventing or inhibiting preterm labor, to date there is no universally effective method that can be used in most patients. As a result, preterm birth will continue to occur and continue to challenge the health care provider. Several medications and hormones have been shown to stimulate endogenous surfactant production in the fetus. Their administration to women at risk of delivering preterm can decrease both the incidence and severity of neonatal RDS. The primary limiting factor with most agents is the need to delay birth for 48 to 72 hours to achieve maximum therapeutic effect. This mandates the obstetric health care provider not only identify parturients who will deliver preterm but also manage their intrapartum course to achieve maximum value from these pharmacologic agents. Lastly, in those patients in whom labor can be neither inhibited nor safely delayed, exogenous surfactant therapy offers real hope particularly to the very low birth weight baby. To obtain maximum benefit in the very premature infant, i.e., less than 30 weeks' gestation, therapy ideally should begin immediately after birth and before the first breath. However, to offer such therapy, patients need to be identified during the intrapartum period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868641 TI - Preventing fetal damage from sexually transmitted diseases. AB - The STDs threaten the reproductive health of women in many ways, ranging from premature births through congenital infections and death. An understanding of the natural history of these diseases permits timely interventions which can mitigate the perinatal damage caused by these infections substantially. Ideally, primary prevention or safer sex will be adopted by sexually active women, thereby reducing the morbidity not only for their offspring but for themselves as well. Antiviral therapy is not yet available for minimizing any hazard of fetal exposure to HPV, HSV, HIV, and hepatitis B viral infections. Early antibiotic therapy should reduce the risk of congenital syphilis and any perinatal hazards associated with chlamydial and gonococcal infections. PMID- 1868642 TI - Intrapartum antibiotic therapy for suspected intraamniotic infection: impact on the fetus and neonate. AB - Acute chorioamnionitis occurs relatively frequently in pregnancy and may result in significant fetal and neonatal morbidity. Although there is no unanimity of opinion regarding the most efficacious antibiotic regimen for the treatment of this complication, there is a consensus, at least among obstetricians, that maternal treatment may have an impact on neonatal outcome. It appears that the fetus and neonate benefit from "intrauterine" treatment. Virtually all antibiotics cross the placenta, and fortunately most are relatively safe for use during pregnancy. PMID- 1868643 TI - Research involving fetal drug therapy: ethical, legal, and practical considerations. AB - Fetal drug therapies have emerged as a promising avenue for the prevention or correction of disease during fetal or immediate postnatal life. Despite slow progress, several medications have been developed for in utero therapy of disorders which relate to fetal and neonatal pulmonary, cardiac, neurologic, and growth disorders. However, ethical and regulatory constraints require protection of the mother and fetus while causing no more than necessary additional risk. Appreciating these constraints will lead to the identification of pragmatic questions which should be answered before evaluating the efficacy and safety of a particular treatment or research proposal. PMID- 1868644 TI - Ovarian masses: serologic markers. PMID- 1868645 TI - Transabdominal and transvaginal sonography of ovarian masses. AB - This chapter outlined the sonographic appearances of most ovarian tumors using both transabdominal and transvaginal sonography. The use of transabdominal and transvaginal sonography for the early detection of ovarian carcinoma seems promising and should be pursued in several institutions as clinical trials. PMID- 1868646 TI - Imaging of ovarian masses: magnetic resonance imaging. PMID- 1868647 TI - Comparison of scintigraphic renal differentials using radiolabeled orthoiodohippurate and glucoheptonate. AB - Differential renal blood flow and parenchymal mass were compared in 50 pairs of scintigraphic studies performed on 44 patients. Background corrected total kidney counts were determined between 1 to 2 minutes following injection of I-123 or I 131 orthoiodohippurate (OIH), and at 1 to 2.5 hours after injection of Tc-99m glucoheptonate (GHA). The OIH and GHA differentials agreed within 5% in 36 studies (72%). When the OIH differentials were symmetric (45% to 55% in each kidney), agreement with the GHA results was complete (17 out of 17). By comparison, 42% (14 out of 33) of studies with asymmetric OIH differentials had a greater than 5% disparity from the GHA split function. Serum creatinine was elevated at the time of 9 out of 14 studies (64%) with OIH/GHA disagreement and 18 out of 36 studies (50%) with OIH/GHA agreement. Of the 14 studies with disparate OIH/GHA differentials, the GHA differential was more symmetric in 10 (71%). When different scinitigraphic measures of differential renal flow and parenchymal mass disagree, this is most likely due to the effects of asymmetric renal impairment rather than to those of global renal dysfunction. PMID- 1868648 TI - Assessment of renal allograft pathology by scintigraphic and ultrasound index markers. AB - The efficacies of two scintigraphic and two sonographic techniques and resultant index values, as markers of renal allograft pathology, were assessed. Index values of 183 combined scintigraphic and sonographic examinations in 47 graft recipients were compared to the pathological diagnosis of transplant biopsies and subsequent clinical outcome. All recipients were studied with baseline imaging techniques postoperatively, again when indicated by predefined clinical criteria, and prior to graft biopsy. The scintigraphic technique involved the calculation of indices of thrombotic activity and cortical graft perfusion. Ultrasound involved determination of the Doppler resistance index of Pourcelot and estimations of graft volume from real time images. A decreased cortical perfusion index was, overall, the most sensitive index of acute or chronic graft pathology, but it lacked specificity. Increased thrombotic and resistance indices were 96% and 86% sensitive for acute vascular rejection and were 82% and 76% specific. Jointly increased thrombotic and resistance indices improved the specificity for acute vascular rejection to 98%. An increase in graft volume of more than 50% over stable values was 100% sensitive and 92% specific for acute interstitial rejection, and 95% specific when paired with a normal thrombotic index. A marked increase in the thrombotic index was 100% sensitive for cyclosporine-induced thrombotic microangiopathy, but only 49% specific. The specificity of a markedly increased thrombotic index for thrombotic microangiopathy improved to 93% when the Doppler resistance index remained normal or was only marginally elevated. None of the scintigraphic or ultrasound indices were helpful for the diagnosis of acute tubular necrosis, chronic rejection, recurrent glomerulopathy, or graft infection. PMID- 1868649 TI - Inaccuracies in quantitative radionuclide renal imaging due to patient position or diverging collimation. AB - Radionuclide renal studies with quantitative measurements in patients confined to intensive care units usually require the use of a 10-inch field-of-view mobile gamma camera and a diverging collimator to image both kidneys simultaneously. The patient must frequently be in the lateral decubitus position so imaging can be performed in the posterior projection. Due to spatial distortion caused by the diverging collimator, variations in detector angulation and kidney depth produce different detection efficiencies for each kidney. Counts in regions of interest over the kidneys were compared as a function of detector angulation and patient position (prone and lateral decubitus). Substantial variations were observed comparing the diverging collimator data to 15-inch field-of view parallel hole acquisitions. Significant variation can also be obtained with parallel hole collimators when the patient's position is changed. PMID- 1868650 TI - Morphine-augmented cholescintigraphy in acute cholecystitis. A satisfactory alternative to delayed imaging. AB - The utility of morphine-augmented cholescintigraphy was reviewed in 32 patients with suspected acute cholecystitis. All patients were administered 2 mg morphine sulfate intravenously when the gallbladder failed to visualize 30 minutes into the study, and imaging continued for up to 60 minutes. Sensitivity for detection of acute cholecystitis was 93% (13 out of 14). Specificity was 78% (14 out of 18). Three of four false-positives occurred in the setting of prolonged fasting and chronic cholecystitis. Cumulative experience suggests that the technique is diagnostically equivalent to imaging for up to 4 hours and that specificity remains incomplete in the setting of prolonged fasting, chronic cholecystitis and other conditions known to affect conventional cholescintigraphy. PMID- 1868651 TI - Scintigraphic diagnosis of right ventricular ischemia. AB - We present a patient with exercise induced right ventricular ischemia demonstrated on stress TI-201 myocardial scintiscan. The patient underwent cardiac catheterization, and subtotal occlusion was found at the proximal right coronary artery. Repeat stress TI-201 scan became normal following the successful percutaneous transluminal coronary angioplasty. PMID- 1868652 TI - Use of Tc-99m MAA in determining the etiology of increasing cyanosis following SVC-PA anastomosis for the hypoplastic left heart syndrome. AB - The hypoplastic left heart syndrome, which characteristically presents in the first few hours of life with cardiovascular collapse, is treated by reconstructive surgery (Norwood's procedure) beginning in the neonatal period. If untreated, more than 95% of infants with this malformation die within the first month of life. The case described involves the development of increasing cyanosis 7 weeks following bilateral superior vena caval-pulmonary artery (SVC-PA) anastomosis in an infant born with a hypoplastic left heart (including aortic and mitral valve stenosis) and an anatomic variant of bilateral superior vena cavae. The use of Tc-99m MAA proved efficacious in quantitating the differential perfusion to each lung, establishing the site of a postoperative stenosis in an anastomotic channel, and documenting systemic perfusion, thus confirming the right-to-left shunt from the superior vena cava to the systemic circulation that resulted in increasing cyanosis. PMID- 1868653 TI - Normalization of left ventricular ejection fraction following resection of pheochromocytoma in a patient with dilated cardiomyopathy. AB - Catecholamine-induced cardiomyopathy associated with pheochromocytoma is a well recognized but rare entity. Both hypertrophic and dilated variants have been described. We report a case of dilated cardiomyopathy associated with a benign pheochromocytoma that showed complete normalization of left ventricular systolic function following removal of the tumor. Serum noradrenaline and dopamine were significantly elevated without elevation in serum adrenaline levels. This may be the first report in which radionuclide ventriculography was used to document the time course of normalization in LVEF following removal of a pheochromocytoma. PMID- 1868654 TI - Comparison of dipyridamole-echocardiography with dipyridamole-thallium scintigraphy for the diagnosis of myocardial ischemia. AB - After an intravenous infusion of dipyridamole (0.56 mg/kg), we performed both echocardiography and thallium scintigraphy in 63 patients who were referred for known or suspected coronary artery disease. Of those patients, 25 returned for coronary arteriography within 1 month after the tests, thus forming the study group for this report. Sensitivity for detection of coronary artery disease, when analyzed region-by-region, was 80% for thallium scintigraphy and 57% for echocardiography, whereas specificity was 85% and 98%, respectively. When evaluating individual patients for the presence or absence of ischemia, we found a sensitivity of 95% for scintigraphy and 58% for echocardiography; corresponding specificities were 50% and 100%. By using arteriography as the gold standard for comparison, it appears that thallium scintigraphy has a significantly higher sensitivity but lower specificity for the detection of coronary artery disease than does echocardiography. Echocardiography may, however, be a useful adjunct to thallium scintigraphy in the evaluation of patients with coronary artery disease. PMID- 1868655 TI - Intense muscle uptake of Ga-67 citrate and Tc-99m MDP in a patient with aplastic anemia. AB - An unusual distribution of Tc-99m MDP and Ga-67 citrate in several muscle groups is described in a 14-year-old boy with aplastic anemia and normal renal function at the time of imaging. Although the patient did not develop musculo-skeletal signs or symptoms, a subsequent autopsy revealed widespread muscle calcification. PMID- 1868656 TI - Tl-201 thyroid imaging in differentiating benign from malignant thyroid nodules. AB - To evaluate the value of Tl-201 thyroid imaging in differentiating benign from malignant thyroid nodules, 58 patients with histologically proven thyroid masses were studied. The nature of the thyroid tumor was initially assessed by Tc-99m scans. Early and delayed Tl-201 thyroid imaging were performed in all patients, and thallium uptake and clearance in the cold nodules were assessed visually. Of the 20 patients with histologically proven malignant nodules, 19 showed increased Tl-201 activity in both the early and delayed images, indicating a sensitivity of 95%. On the other hand, 35 out of the 38 patients with benign nodules showed no increased thallium activity in the nodules on the delayed images, indicating a specificity of 92%. When early thallium images were analyzed separately, the sensitivity was 100% but the specificity was only 37%. By combining early and delayed Tl-201 images, differentiation between benign and malignant cold nodules is feasible. False-positive and false-negative cases will be discussed. PMID- 1868657 TI - Intracranial extramedullary hematopoiesis. CT and bone marrow scan findings. AB - This case concerns a patient with intracranial extramedullary hematopoiesis (EH) suspected on a CT scan and subsequently confirmed with In-111 chloride and Tc-99m SC bone marrow scans. The bone marrow scans also provided additional information by demonstrating other sites of EH in the paravertebral tissues and bone marrow expansion into the distal extremities. PMID- 1868658 TI - Whole body retention of Tc-99m phosphate in Paget's disease of bone. AB - The effectiveness of the 24-hour whole body retention of Tc-99m MDP in monitoring disease activity was evaluated in 58 patients with Paget's disease of bone. Patients had baseline 24-hour retention studies, bone scans, radionuclide bone blood-flow studies, and alkaline phosphatase and OH-Proline level measurements. Increased retention of Tc-99m MDP was present in 88% (51/58) of individuals while alkaline phosphatase and OH-Proline were respectively elevated in 100% (58/58) and 64% (35/55) of patients. Forty-seven examinations were further obtained to evaluate changes in retention with therapy. Retention correctly reflected response to treatment in 89.3% of follow-ups versus 85.1% with alkaline phosphatase (n = 47). It was accurate in 90.9% of patients versus 75% for OH Proline (n = 44). We conclude that the retention study, while not absolutely correlative with Pagetic activity, still is useful in grading the condition. It is a simple additional step that monitors the global severity of lesions localized on bone scans. PMID- 1868659 TI - Incidental finding of crossed renal ectopia diagnosed on bone scan. PMID- 1868661 TI - The serendipitous diagnosis of a pseudoaneurysm by the three-phase bone scan. PMID- 1868660 TI - Bone marrow scintigraphy and MRI in a patient with osteopetrosis. PMID- 1868662 TI - Focal fatty infiltration of the liver. Evaluation by planar and SPECT images. PMID- 1868663 TI - Prominent cisterna magna. Tc-99m HMPAO and MRI correlation. PMID- 1868664 TI - Unusual pelvic activity found on bone scan. PMID- 1868665 TI - Tc-99m HMPAO leukocyte uptake in articular gout. PMID- 1868666 TI - Role of bone scanning in pulmonary alveolar microlithiasis. Report of two cases. PMID- 1868667 TI - Pathology of the temporo-mandibular joint and its treatment in the first half of the 19th century. 1. PMID- 1868668 TI - The birth of the specialty of orthodontics. 1. PMID- 1868669 TI - Queen Victoria and the dentists. PMID- 1868670 TI - Geographical variations in dental disease. PMID- 1868671 TI - The value and effects of implementing an essential drugs list in the Lagos University Teaching Hospital. PMID- 1868672 TI - An indicator-based program for improving medication use in acute care hospitals. PMID- 1868673 TI - Effect of the requirement for triplicate prescriptions for benzodiazepines in New York State. PMID- 1868674 TI - Age-related differences in hepatic drug clearance in children: studies with lorazepam and antipyrine. AB - The disposition of intravenous antipyrine and lorazepam, administered as model substrates for hepatic oxidative metabolism and conjugation, was evaluated in 50 children (mean age, 7.8 years; range, 2.3 to 17.8 years) with acute lymphocytic leukemia in complete remission and compared with a group of ten healthy adults. Antipyrine clearance normalized to body weight was significantly greater in children than in adults (0.91 versus 0.59 ml/min/kg; p = 0.012), but was not different when normalized to body surface area. In contrast, lorazepam total clearance (CL) and unbound clearance (CLu) normalized to body weight were not significantly different between children and adults but were smaller in children when normalized to body surface area (CL = 31.9 versus 40.6 ml/min/m2, p = 0.036; CLu = 352 versus 485 ml/min/m2, p = 0.010). The mean lorazepam fraction unbound in children was 0.087, which was not different from adult volunteers (0.084). This study has identified significant differences between children and adults in the disposition of these two compounds, with higher milliliter per minute per kilogram clearance for antipyrine but not lorazepam. PMID- 1868675 TI - Multiple-dose pharmacokinetics of ganglioside GM1 after intravenous and intramuscular administration to healthy volunteers. AB - Ganglioside GM1 multiple-dose pharmacokinetics were investigated in five healthy male volunteers. Doses of 100 mg were administered either intravenously or intramuscularly for 21 days, and the washout was followed-up for a further 21 days. The highly specific binding of the beta-subunit of cholera toxin was used to quantify ganglioside GM1 levels in plasma, urine, and feces. This dose regime increased the ganglioside GM1 steady-state plasma levels two to three orders of magnitude above the endogenous levels of 0.132 mg/L (coefficient of variation, 8.9%). Large and variable amounts of ganglioside GM1 were found in feces before and during treatment without relation to the dosage. No ganglioside GM1 could be detected in urine at any time. Plasma kinetics were linear with a biexponential disposition. Exogenously administered ganglioside GM1 was confined mainly to the blood volume as indicated by a steady-state volume of distribution of 6.98 +/- 3.57 L and appears to be excreted mainly in the form of metabolites. The total clearance was very slow at 1.61 +/- 0.37 ml/min. Absorption after intramuscular administration was slow (time to reach maximum concentration greater than 12 hours) and yielded steady-state concentrations somewhat lower compared with the intravenous infusion. PMID- 1868676 TI - Increased suppression of exercise-induced increase in renin by propranolol in Chinese subjects. AB - Sensitivity to the hypotensive effect of propranolol differs between Chinese subjects and white subjects. To explore the pharmacodynamic explanation for this difference, eight Chinese subjects (age range, 25 to 42 years) and eight white subjects (age range, 22 to 36 years) were given single doses of 10, 20, 40, and 80 mg propranolol on separate occasions at least 3 days apart. Heart rate, mean blood pressure, norepinephrine, epinephrine, and plasma renin activity were measured at the end of treadmill exercise 2 hours after medication was administered. Propranolol produced a concentration-dependent reduction in mean blood pressure and heart rate in both groups. Concentration-response curves were shifted significantly to the left in Chinese subjects, confirming the increased sensitivity to propranolol of the Chinese. The baseline exercise plasma renin activity was twofold higher (p less than 0.05) in Chinese than in white subjects. The sensitivity to beta-blockade-induced suppression of plasma renin activity was increased in the Chinese, which resulted in a sevenfold higher concentration being required in white subjects than in Chinese to produce the same 50% suppression of exercise plasma renin activity (84.8 +/- 23.2 versus 12.7 +/- 7.4 ng/ml, p less than 0.05). The reduction in exercise heart rate and mean blood pressure produced by propranolol were well correlated to the reduction in exercise plasma renin activity in both populations. There was no significant effect of either race or propranolol on plasma catecholamine concentration after exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868677 TI - Effects of caffeine on tobacco withdrawal. AB - Smoking cessation increases caffeine blood levels, and this has been hypothesized to cause some of the symptoms of tobacco withdrawal (e.g., anxiety and insomnia). To test this hypothesis, 10 coffee drinkers who smoked cigarettes were entered into a completely within-subjects experimental design in which the effects of caffeine dose (0, 50, and 100 mg/coffee serving) and smoking status (smoking versus abstinence) were examined over a 4-day period. Self-reported and observed measures of tobacco withdrawal, caffeine withdrawal, and intoxication, as well as psychomotor tasks and vital signs, were completed daily; blood was drawn at the end of each period. Temporary abstinence produced typical withdrawal symptoms but did not significantly increase caffeine blood levels. Caffeine did not increase the severity of symptoms but did decrease the severity of withdrawal-induced hunger. These findings suggest that, in the absence of increased blood levels, caffeine does not increase the severity of tobacco withdrawal. PMID- 1868678 TI - Comparison of the effect of temafloxacin, ciprofloxacin, or placebo on cerebral blood flow, glucose, and oxygen metabolism in healthy subjects by means of positron emission tomography. AB - STUDY OBJECTIVE: To determine the cause of the central nervous system effect of the fluorinated quinolones temafloxacin and ciprofloxacin by measuring cerebral blood flow and metabolism by use of positron emission tomography. DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study. PATIENTS: The patients were 13 healthy, nonsmoking volunteers whose ages ranged from 18 to 40 years. RESULTS: We measured brain blood flow and metabolism by use of positron emission tomography before and after a five-dose course of 750 mg ciprofloxacin, 600 mg temafloxacin, or placebo given every 12 hours. Quinolone administration produced no significant effect on visual (qualitative) reading of the positron emission tomography scans. CONCLUSIONS: We conclude that short-term administration of temafloxacin, ciprofloxacin, or placebo does not significantly alter cerebral glucose or oxygen metabolism. Subjects treated with ciprofloxacin demonstrated a significant decrease in brain blood flow compared with baseline and with temafloxacin- or placebo-treated subjects. PMID- 1868679 TI - A comparison of the sensitivities of adaptive tracking, eye movement analysis and visual analog lines to the effects of incremental doses of temazepam in healthy volunteers. AB - The effects of single oral doses of 5, 10, and 20 mg temazepam were evaluated with the adaptive tracking test, analysis of smooth-pursuit and saccadic eye movements, and visual analog lines in a placebo-controlled, double-blind, crossover experiment with 12 healthy volunteers. Pharmacodynamic testing was performed until 10 hours and pharmacokinetics were evaluated until 24 hours. Temazepam, 20 mg, caused effects in all tests, with peak effects occurring at 30 minutes. The 10 mg dose caused effects on saccadic eye movements and subjective scores of alertness, whereas 5 mg temazepam was detected only by analysis of saccadic eye movements. Linear relationships between plasma concentrations and effects were found in nine subjects for saccadic peak velocity and eight subjects for subjective scores of alertness. The results of this study demonstrate manifest differences in the sensitivities of performance tests and stress the importance of validation of methods when effects of drugs on human performance are studied. PMID- 1868680 TI - Measuring compliance in methadone maintenance patients: use of a pharmacologic indicator to "estimate" methadone plasma levels. AB - A quantitative indicator of compliance is not available for methadone--the drug of choice for the treatment of opioid addiction. We successfully used low-dose phenobarbital (a valid pharmacologic indicator) to measure compliance by incorporating the drug into the methadone medication of patients attending an addiction unit. Plasma phenobarbital and methadone concentrations were measured in 20 (11 clinic-based and 9 community-based) patients receiving long-term treatment with the phenobarbital level-to-dose ratio, together with interviews, to validate methadone measurements and to monitor compliance. Patients attending the unit on a daily basis and who consumed their medication in the clinic were substantially more compliant than community-based patients. Laboratory measurements of phenobarbital and methadone helped to identify the use of illicit methadone, as well as incorrect self-administration, such as the consumption of several days' dosage at one time. PMID- 1868682 TI - Evolution in molecular structure and adaptive variance in metabolism. AB - 1. A hypothesis is advanced to the effect that all metabolites, even minor ones, are expressed as a result of stimuli and are directed against or support actions on receptor systems. 2. In particular the hypothesis emphasizes the dynamic character of the secondary metabolite pattern as a function of physiological or environmental conditions and that the variations observed reflect the evolution of receptors. 3. Predictions based on this principle are experimentally verifiable. 4. The hypothesis has major implications in the entire area of life sciences. PMID- 1868681 TI - Antibiotic use after cefuroxime prophylaxis in hip and knee joint replacement. AB - The amount of additional antibiotics measured by defined daily dose (DDD) methods after 2651 hip and 362 knee replacements was assessed after prophylaxis with one or three doses (1502/1511 patients) of cefuroxime. No differences were observed between the two regimens with respect to total amount, type, indication, and duration of additional antibiotics. The incidence of joint sepsis did not differ significantly between the two trial arms, but the sample was too small for definite conclusions. There were 11.4 DDD/100 bed days of additional antibiotics used in 21% of patients after hip replacement and 15.7 DDD/100 bed days in 31% after knee replacement. For wound problems, 3.8 and 6.9 DDD/100 bed days were given in the hip- and knee-replacement groups. For distant infection, 6.5 DDD/100 bed days was administered in both groups. Duration of therapy varied only in relation to indication. Prescribed were penicillins (43% to 50%), sulfonamides (18%), cephalosporins (10% to 16%), and nitrofurantoin (8% to 13%); drug use was related to the type of infection. PMID- 1868683 TI - Malaria and Leishmania parasites share the knob-associated histidine-rich protein gene sequences. AB - 1. The main coding region of the knob-associated histidine-rich protein (KAHRP) gene of Plasmodium falciparum hydridized with genomic DNA of Leishmania donovani. 2. A total of five EcoRI fragments of various sizes (7.5, 5.5, 3.2, 0.75 and 0.56 Kb) were recognized by this probe, under lower stringent conditions. However, under a higher stringency of washing, two of the smallest fragments were washed away. 3. Out of these EcoRI fragments, the 5.5 Kb band showed a maximum homology with the probe which contains the histidine-rich coding sequences, whereas the 3.2 Kb band showed none. Thus there is a possibility that the Leishmania parasite also contains a KAHRP-like gene. PMID- 1868684 TI - Whey proteins of the common brushtail possum (Trichosurus vulpecula): isolation, characterization and changes in concentration in milk during lactation of transferrin, alpha-lactalbumin and serum albumin. AB - 1. Transferrin and serum albumin were purified from both whey and serum and alpha lactalbumin was purified from whey from the common brushtail possum (Trichosurus vulpecula). 2. The N-terminal amino acid sequences for transferrin and serum albumin were identical for the proteins from both whey and serum and showed homologies with transferrin or serum albumin from other species. 3. N- and C terminal regions of possum alpha-lactalbumin were also sequenced and have been compared with wallaby alpha-lactalbumin and several eutherian alpha-lactalbumins. 4. Antisera raised to each of the three proteins were species specific and Western blots further confirmed the identity of the serum and whey transferrins and serum and whey serum albumins. 5. The concentration of transferrin increased ten-fold between days 110 and 130 of lactation, whereas no significant changes in the concentration of alpha-lactalbumin could be detected after day 60. PMID- 1868685 TI - The isolation and characterization of the major glutathione S-transferase from the squid Loligo vulgaris. AB - 1. The major glutathione S-transferase (GST) from the common squid Loligo vulgaris has been purified and shown to be a homodimer of subunit molecular mass 24,000 and pI 6.8. 2. It has high activity towards 1-chloro-2,4-dinitrobenzene, p nitrobenzyl chloride, 4-hydroxynon-2-enal and linoleic acid hydroperoxide, low activity with 1,2-dichloro-4-nitrobenzene and no activity with ethacrynic acid, trans-4-phenyl-3-buten-2-one and 1,2-epoxy-3-(p-nitrophenoxy)propane. 3. The L. vulgaris GST did not cross-react with any of the available polyclonal antibodies raised against mammalian GSTs. 4. Forty amino acids of its N-terminal sequence have been determined. 5. Its activities and primary structure are compared with related proteins from other species. PMID- 1868686 TI - Donkey and horse alpha 1 B-glycoprotein: partial characterization and new alleles. AB - 1. The donkey postalbumin protein has been shown to be the equivalent of human alpha 1 B-glycoprotein by protein immunoblotting and N-terminal amino acid sequence. 2. The horse A1B system (already identified as the homologue of human alpha 1 B-glycoprotein) and the donkey alpha 1 B-glycoprotein were characterized further for terminal sialic acid content, isoelectric point, amino acid composition and affinity for the dye-ligand, Cibacron Blue F3GA (known to bind human alpha 1 B-glycoprotein). 3. Two new alleles in the horse A1B system were found, bringing the total number of alleles to five. No polymorphism was found in the donkey alpha 1 B system. 4. As expected the first 20 N-terminal residues of the donkey and horse proteins are highly conserved with only two differences being found. 5. The polymorphism of the horse alpha 1 B-glycoproteins may be due in part to differing numbers of terminal sialic acid residues and the higher electrophoretic mobility of the donkey alpha 1 B-glycoprotein may be due in part to increased sialylation. 6. The horse and donkey alpha 1 B-glycoproteins exhibited differences in affinity for the dye-ligand, Cibacron Blue F3GA, with the donkey alpha 1 B-glycoprotein not being bound. PMID- 1868687 TI - Hybrid formation of rabbit and rat hepatic glutathione S-transferases. AB - 1. A reconstitution experiment resulted in the formation of new proteins between limited combinations of rat and rabbit hepatic glutathione S-transferases: AA(subunit composition: YcYc) and R3b(Y3Y3), Lig(YaYa) and R3b(Y3Y3), and A(Yb1Yb1) and R2(Y2Y2). 2. It was demonstrated that the new protein formed between R2 and A had the subunit composition of Y2Yb1, suggesting a hybrid of rabbit (R2) and rat isozyme (A). 3. This hybrid protein showed intermediate spec. acts between those of R2 and A when either 1-chloro-2,4-dinitrobenzene (CDNB) or 1,2-dichloro-4-nitrobenzene (DCNB) was employed as the substrate. PMID- 1868688 TI - Serum high-density lipoproteins in the crab, Cancer antennarius--III. Density gradient profiles and lipid composition of subclasses. AB - 1. Prestaining the serum total lipoprotein (LP) fraction and density-gradient ultracentrifugation revealed up to five LPs, all in the high-density class (HDL; 1.187 greater than d greater than 1.080 g/ml). These are group-designated as HDL1, HDL2 and HDL3, lowest to highest buoyant density, respectively. The number and precise density of the LPs varied with individual crab and were not gender specific. 2. The percentage of total mass due to triacylglycerides was progressively higher from HDL1 and HDL3, whereas that of phospholipids, cholesterol and combined fat was progressively lower. The percentage mass of combined fat was higher in females than males. 3. As in hemolymph, the LP of eggs was entirely HDL; instances of each HDL subclass were seen, but HDL3 was predominant. Compared with serum HDL, egg HDL was strikingly low in triacyglyceride mass and relatively high in protein. 4. Hemolymph HDL titers of individual females varied independently with egg size through most of the year, but was positively correlated with the egg size in October to December when 2-3 fold increases in HDL titer occur in the female population. PMID- 1868689 TI - The effect of cold exposure on rat liver mitochondrial respiratory capacity. AB - 1. The effect of cold exposure on the respiratory capacity of rat liver mitochondria has been studied using succinate as the substrate. 2. The mitochondria obtained in this study were well coupled, as shown by the RCR and ADP/O ratios. 3. In addition, durohydroquinone was used to eliminate the regulation of substrate supply. Likewise, we measured uncoupled respiration to evaluate the maximal electron flow through the respiratory chain. 4. We found that oxygen consumption using succinate or durohydroquinone + FCCP as substrates, as well as ATP production were not affected by cold exposure. 5. Our results also show that, when succinate is used, the maximal capacity of the respiratory chain is measured. 6. The data obtained do not support a role of the electron transport chain as a target of cold action. PMID- 1868690 TI - Gastrin in fetal and neonatal pigs. AB - 1. The concentration and molecular profile of gastrin were examined in plasma and tissue extracts of fetal and neonatal pigs from 93 days gestation up to 12 weeks of age and also in the fetal gastric contents. 2. Gastrin was present in the gastrointestinal tract and plasma of fetal pigs at 93 days gestation. The concentration in both plasma and antral extracts increased progressively up to birth and continued to rise postnatally, reaching a peak at about 3 weeks of age in plasma and 6 weeks in the antrum. 3. In blood the major molecular form of gastrin was G34 (up to 80%), while in the antrum the major form was G17 (66-91%). The percentage of G34 in the antrum was highest in later gestation (21%), and reached adult proportion by 8 weeks of age (4%). 4. A considerable amount of gastrin, chiefly G17, was detected in the fetal gastric contents. Synthetic human G17 was stable in fetal gastric contents when incubated at 37 degrees C for 60 min, although, when incubated with gastric contents from a sow, it disappeared within 5 min. 5. It is suggested that the presence of gastrin in fetal gastric contents may be important in stimulation of fetal gut development. PMID- 1868691 TI - Kinetics of the multi-step catalytic degradation of a polymer to its constituent subunits. AB - The stepwise catalytic degradation of a polymer to its constituent subunits results in many molecules of polymers of shorter chain length. Using the Law of Mass Action, ordinary differential equations for each species can be obtained from the set of elementary reactions and these can be integrated to obtain species concentrations as a function of time. A special case of catalytic degradation of polymers, in which one subunit is released at each step, is examined. A mathematical dissertation on the kinetics of the series of reactions involved is presented. The solution of the set of differential equations involve tedious computations and cannot be easily adapted to the analysis of experimental data. Two additional methods of analysis are described. The first one makes use of the property that for any intermediary polymer whose initial and final concentrations are zero, the integral of its concentration with respect to time is inversely proportional to the degradation rate constant. Stepwise calculation of the rate constants can thus be obtained by determining the area under the concentration-time trajectories while the degradation rate constant of the first polymer is known. The second method makes use of the property that the maximum concentration attained by any individual intermediary polymer is inversely proportional to its degradation constant. These methods have the advantage of being simple since the degradation constants can be obtained stepwise from experimental data. PMID- 1868692 TI - A syntactic analysis method for sinusoidal tracking eye movements. AB - A syntactic method for the recognition of sinusoidal eye movements is presented. The method is based on a piecewise transformation of an eye movement signal to strings of a formal language and use of a formal grammar which generates the formal language. Gain and phase parameters of sinusoidal eye movements between a stimulus and its response are computed after the recognition of eye movements and after removing corrective saccades from the transformed signal. The method is used at an otoneurological laboratory. PMID- 1868693 TI - Parallelizing genetic linkage analysis: a case study for applying parallel computation in molecular biology. AB - Parallel computers offer a solution to improve the lengthy computation time of many conventional, sequential programs used in molecular biology. On a parallel computer, different pieces of the computation are performed simultaneously on different processors. LINKMAP is a sequential program widely used by scientists to perform genetic linkage analysis. We have converted LINKMAP to run on a parallel computer, using the machine-independent parallel programming language, Linda. Using the parallelization of LINKMAP as a case study, the paper outlines an approach to converting existing highly iterative programs to a parallel form. The paper describes the steps involved in converting the sequential program to a parallel program. It presents performance benchmarks comparing the sequential version of LINKMAP with the parallel version running on different parallel machines. The paper also discusses alternative approaches to the problem of "load balancing," making sure the computational load is shared as evenly as possible among the available processors. PMID- 1868694 TI - Methodology for generating continuous prediction equations for pulmonary function measures. AB - A mathematical procedure is described for fitting piecewise linear equations constrained to join at estimable multiple junctions or breakpoints. The model parameters, a combination of both linear and nonlinear, are estimated using a "Separable Least Squares" algorithm. In this algorithm the linear parameters, estimated using the General Linear Model, are nested within the iterations of a nonlinear optimization routine. This formulation allows additional covariates to be included in the model and can be easily expanded to include any number of line segments, both linear and nonlinear. The procedure is demonstrated by estimating continuous lung function reference equations for healthy normal subjects. Comparison of these reference equations with previously published equations derived for the same subjects, illustrates the advantages of having continuous equations throughout the age range of the data. PMID- 1868695 TI - Heuristic determination of quantitative data for knowledge acquisition in medicine. AB - Knowledge acquisition for medical knowledge bases can be aided by programs that suggest possible values for portions of the data. The paper presents an experiment which was used in designing a heuristic to help the process of knowledge acquisition. The heuristic helps to determine numerical data from stylized literature excerpts in the context of knowledge acquisition for the QMR medical knowledge base. Quantitative suggestions from the heuristics are shown to agree substantially with the data incorporated in the final version of the knowledge base. The experiment shows the potential of knowledge base specific heuristics in simplifying the task of knowledge base creation. PMID- 1868696 TI - Automated detection of breast tumors using the asymmetry approach. AB - A method for automated detection of breast tumors in mammograms is presented. The method uses the asymmetry principle: Strong structural asymmetries between corresponding regions in the left and right breast are taken as evidence for the possible presence of a tumor in that region. Asymmetry detection is achieved in two steps. First, mammograms are aligned, compensating for possible differences in size and shape between the two breasts. Second, asymmetry between corresponding positions is determined using a combination of several asymmetry measures, each responding to different types of asymmetries. Results obtained with a set of mammograms indicate that this method can improve the sensitivity and reliability of systems for automated detection of breast tumors. PMID- 1868697 TI - A new method for fetal ECG detection. AB - Presented in this work is the theoretical basis of a new method we propose for the analysis of fetal ECG (FECG). This method is intended to detect the fetal HR from a weak FECG signal, and to supply us with an average FECG complex. The FECG signals studied in this work were recorded from the maternal abdominal wall. The core of our method is the computation of a triple parametric transform, using analyzing functions which have a greater correlation with the ECG signal than the correlation of the standard sine and cosine functions used in a Fourier transform. The functions used are trains of square waves characterized by the width of the square wave, their periodicity, and some initial phase value. This method, applied here to a medical problem, can be more generally applied to handle weak quasiperiodic sharp signals of any origin. PMID- 1868698 TI - Lymphocyte transformation and thiuram sensitization. AB - The use of a lymphocyte transformation test (LTT) to confirm allergic contact dermatitis from thiurams has been investigated. The responses of peripheral blood mononuclear cells (PBMC) from thiuram-sensitive and non-sensitive individuals following culture with dimethylcarbamoyl-protein (human serum albumin; HSA) and dimethylthiocarbamoyl-HSA conjugates has been compared. Only PBMC from those patients who were patch-test-positive with thiuram-mix and sensitized to tetramethylthiuram monosulphide (TMTM) or TMTM and tetramethylthiuram disulphide (TMTD) exhibited significant proliferative responses to these conjugates. Thiuram patch-test-negative patients and control donors with no history of allergic contact dermatitis failed to mount a significant response to any concentration of either conjugate. Two of the thiuram-sensitive patients were also nickel-patch test-positive, and PBMC isolated from these donors, but not from nickel-patch test-negative patients, proved positive in a nickel LTT. The data reveal that relevant hapten-protein conjugates are capable of provoking specific human lymphocyte proliferative responses in vitro, and that, using this technique, the LTT can, in principle, be used for the investigation and/or diagnosis of skin sensitization to lipophilic contact allergens. PMID- 1868699 TI - Quantification of allergic and irritant patch test reactions using laser-Doppler flowmetry and erythema index. AB - The laser-Doppler blood flow and erythema index were assessed in 16 patch test reactions caused by irritants (1% aq. sodium lauryl sulphate and 1% aq. benzalkonium chloride) and in 13 varied allergic reactions, at 2 or 4 days. Both irritant and allergic responses produced statistically significant increases in laser-Doppler flow index and erythema index compared to control sites (p less than 0.05 or less, using the Wilcoxon rank-sum test). A disproportionately greater increase in erythema index than in laser-Doppler flow was seen in mild irritant reactions, compared to allergic, though the two could not be reliably distinguished by these tests. 2 non-allergic nickel sulphate sites produced an increase in both blood flow and erythema without any clinical change. Petrolatum alone produced no significant change in either measurement. The laser-Doppler flow showed an overall correlation with the erythema index (product moment method; r = 0.55, p less than 0.001), but there was little correlation between these indices and patch test reactivity as judged clinically by conventional scoring. Generally, allergic and irritant patch test reactions could not be differentiated on the basis of laser-Doppler flow or erythema index. However, the disproportionate increase in erythema index over laser-Doppler flow index for mild irritant responses warrants further study in other irritant models. PMID- 1868700 TI - A probable role for vaccines containing thimerosal in thimerosal hypersensitivity. AB - We patch tested 141 patients with 0.05% aq. thimerosal and 222 patients with 0.05% aq. mercuric chloride, including 63 children. The frequency of positive patch test reactions to thimerosal was 16.3%. There was a marked preponderance in the young age groups after vaccination, while none of 36 infants (aged 3-48 months) reacted to thimerosal. Positive reactions to mercuric chloride were found in 23 (10.4%) of 222 patients. We also sensitized guinea pigs with diphtheria pertussis-tetanus (DPT) vaccine containing 0.01% thimerosal and succeeded in inducing hypersensitivity to thimerosal. From patch testing in humans and animal experiments, it is suggested that 0.01% thimerosal in vaccines can sensitize children, and that hypersensitivity to thimerosal is due to the thiosalicylic part of the molecule and correlates with photosensitivity to piroxicam. PMID- 1868701 TI - The loss of contact sensitization in man. AB - Little is yet known about the duration of contact sensitivity, but frequent exposure of a target to allergen seems to reduce skin reactivity. The aim of this study was to study the persistence of a specific contact sensitivity in 66 patients with alopecia areata, previously sensitized to DNCB (31 patients) and SADBE (35 patients) between 1978-1985. Patch tests were performed with 0.020 ml of different concentrations of DNCB or SADBE in acetone (0.05%, 0.10%, 0.20%, 1%). The results were read in a standardized manner. Of 66 patients, 47 (71%) had positive reactions and 19 (29%) negative. 8 of the 19 negative patients had been treated with DNCB, 11 with SADBE. Approximately 1/3 of the patients previously sensitized had lost their original sensitivity, and this did not seem to be time dependent. This phenomenon seemed to be clinically correlated because the majority of the patients were from the "low responders" group. We think that acquired unresponsiveness to topical antigen in man is a possible phenomenon, but that it occurs more rarely than in mice and guinea pigs. PMID- 1868702 TI - Sensitivity to thimerosal and photosensitivity to piroxicam. AB - 17 patients allergic to thimerosal, with no previous history of photosensitivity or piroxicam ingestion, 2 patients with piroxicam-induced photosensitivity, and 10 controls were patch or photopatch tested, with 1 or more of the following: thimerosal, thiosalicylic acid, irradiated and non-irradiated solutions of piroxicam alone, L-cysteine alone and piroxicam plus L-cysteine, and piroxicam in petrolatum., The results of the tests supported the hypothesis that there are cross-reactions between thiosalicylic acid and prioxicam, a photosensitizer. The mechanism of the cross-reactions may involve photoproducts of piroxicam and L cysteine, as patients allergic to thiosalicylic acid, who have positive photopatch tests to piroxicam, also had positive patch tests to the irradiated solution of piroxicam plus L-cysteine. PMID- 1868703 TI - Tussockosis: an outbreak of dermatitis caused by tussock moths in Singapore. AB - An outbreak of acute pruritic rash occurred in March 1990 among 141 residents of a high-rise public housing estate in Bukit Panjang, Singapore. The typical rash consisted of urticarial lesions distributed over the limbs and trunk. The outbreak was associated with a transient increase in tussock moths in the residential estate following an unusual, short dry spell. The aetiology was established when patch tests with crude moth material produced similar eruptions in 5 out of 7 adult volunteers between 40 min and 12 h. Pharmacological experiments with an aqueous extract of moth hairs in isolated guinea pig ileum elicited a response similar to that induced by histamine. PMID- 1868704 TI - Contact sensitivity (allergic contact dermatitis) to bis(tri-n-butyltin) oxide in mice. AB - Contact sensitivity (allergic contact dermatitis) to bis(tri-n-butyltin) oxide (TBTO) was demonstrated in the mouse. TBTO (in an acetone:olive olive oil vehicle) or acetone:olive oil alone (as a control) were applied to the shaved flank under an occlusive patch and animals were challenged on the dorsum of the ear 6 days later. Ear swelling was then measured using an engineer's micrometer, 2, 24, 48 or 72 h thereafter. Significant differences in ear swelling between control and TBTO-sensitized animals were found 24 h after challenge: thereafter the elicitation reaction declined rapidly whilst irritant swelling in control animals increased. Maximal elicitation of TBTO sensitivity could only be elicited by concentrations of TBTO that caused irritation. In a separate experiment, a single application of TBTO to the ears of naive animals provoked increase in auricular lymph node weight, cell yield and proliferation of lymph node cells during overnight culture. These data support the conclusion that TBTO is a contact sensitizer and illustrate the potential usefulness of the quantitative methods of contact sensitivity assessment which have been developed in the mouse. PMID- 1868705 TI - Ultrasound B scanning with image analysis for assessment of allergic patch test reactions. AB - Assessment of patch test results has been performed visually and using ultrasound in the B mode. A positive test site has a typical ultrasonographic appearance, presenting a uniform hypoechogenic area in the dermis. In this zone, the mean amplitude of ultrasound reflection peaks decreases, and the extension of this area increases, together with the intensity of the eczematous reaction. A close correlation has been shown between visual scoring, amplitude decrease and surface increase of the hypoechogenic area. This technique seems to provide a reproducible system for the evaluation of patch tests. PMID- 1868706 TI - Contact dermatitis from eugenol in mouthwash. PMID- 1868707 TI - Contact dermatitis from oak moss. PMID- 1868708 TI - Allergic contact conjunctivitis without eyelid involvement. PMID- 1868709 TI - Pigmented photoallergic contact dermatitis from musk ambrette. PMID- 1868710 TI - Allergic contact dermatitis from Codivilla's spring. PMID- 1868711 TI - Contact dermatitis from nickel and cobalt in a contact lens cleaning solution. PMID- 1868712 TI - Hydrangenol, a strong contact sensitizer found in hydrangea (Hydrangea sp.; Hydrangeaceae). PMID- 1868713 TI - Quantification of irritant contact dermatitis in vivo: comparison of the Dermatest system with the evaporimeter. PMID- 1868714 TI - Patch testing with fragrance-mix and its constituents: discrepancies are largely due to the presence or absence of sorbitan sesquioleate. PMID- 1868715 TI - Patch testing with amalgam at various concentrations. AB - 27 patients with positive D3 reactions on patch testing to 3 mercury screening allergens were patch tested with 13 mercury patch test preparations, 6 inorganic and 7 organic, and amalgam 20% pet. The 13 patients (all women) showing positive reactions to 20% amalgam were then patch tested to reducing concentrations. 2 patients reacted down to 1%, 4 down to 2%, 4 down to 5%, 2 down to 10% and 1 only to 20%, a total of 10 of the 13 patients therefore reacting to the 5% concentration of amalgam. The appropriate patch test concentration of amalgam is discussed and the clinical significance and female preponderance of amalgam reactivity suggested as being worthy of further investigation. PMID- 1868716 TI - Patch test responses to rockwool of different diameters evaluated by cutaneous blood flow measurement. AB - Rockwool is a man-made mineral fiber used mainly for insulation, which can cause mechanical skin irritation. This study was performed to evaluate the irritant potential of rockwools of different diameters and to compare the change of blood flow, measured by laser Doppler flowmetry, at different patch test occlusion times with rockwools. Rockwool A (mean diameter 4.20 +/- 1.96 mu) was more irritating than rockwool B (mean diameter 3.20 +/- 1.5 mu). The difference was more clearly observed in a 48-h patch test than in an 8-h or 24-h test. We concluded that laser Doppler blood flow measurement was a useful experimental tool for the evaluation of irritant patch test responses to mechanical irritants like rockwool, and that 48 h or more of occlusion time was necessary to produce irritant patch test responses to certain types of rockwool. PMID- 1868717 TI - alpha-Peroxyachifolid and other new sensitizing sesquiterpene lactones from yarrow (Achillea millefolium L., Compositae). AB - Yarrow, Achillea millefolium L., is one of the commonest weeds of the Compositae family. Cases of allergic contact dermatitis have been described since 1899. Although 10 sesquiterpene lactones (SL) and 3 polyines have previously been identified, the sensitizers of yarrow have escaped detection. A reinvestigation of short ether extracts of yarrow revealed the presence of 5 unsaturated hitherto unknown guaianolides of peroxide character. The main SL, identified as a strong sensitizer in guinea pig sensitization experiments, was named alpha peroxyachifolid. The minor SL also contribute marginally to the sensitizing capacity, while other known yarrow constituents like dehydromatricaria ester and pontica epoxide appear to play no role. A 5-year follow-up (1985-1990) of Compositae-sensitive patients showed that more than 50% reacted when tested with a short ether extract of yarrow. Exacerbation of the patch test sites by irradiation with UV light was never observed. PMID- 1868719 TI - Allergic contact dermatitis from non-diglycidyl-ether-of-bisphenol-A epoxy resins. AB - In addition to previously presented patients with allergic contact dermatitis from cycloaliphatic epoxy resins (ERs), during 1974-1990, we have seen 4 patients with allergic contact dermatitis (ACD) caused by products containing uncured non diglycidyl-ether-of-bisphenol-A ER. The patients were negative on patch testing with the standard ER based on diglycidyl ether of bisphenol A (DGEBA-ER). The following non-DGEBA-ERs were included in the causative agents: heterocyclic dimethylhydantoin ER, phenol novolak ER, and brominated ER. We were unable to specify the type of ER in an epoxy primer used by the 4th patient. Apart from the ACD caused by the brominated ER, 1 of the patients also had IgE-mediated occupational rhinitis caused by methyl hexahydrophthalic anhydride (MHHPA), an epoxy hardener. The diagnosis was verified by positive prick tests and specific IgE determinations with MHHPA. Intense rhinitis evoked by a bronchial challenge with MHHPA confirmed the diagnosis. We stress the importance of performing patch testing with the relevant epoxy resins to which the patient has been exposed, in addition to patch testing with the standard ER. PMID- 1868718 TI - Allergic contact dermatitis from para-tertiary-butylphenol-formaldehyde resin (PTBP-FR) in athletic tape and leather adhesive. AB - 4 girls with severe allergic contact dermatitis from a brand of athletic tape and a cobbler with allergic contact dermatitis from leather adhesive are presented. Alkylphenol resin with unknown chemical structure had been compounded in both products. One of the girls developed foot dermatitis later from the adhesive used on the inside of new sneakers. By patch testing and chemical analysis of alkylphenol resin and the products, the 5 patients were given a specific diagnosis of allergic contact dermatitis from PTBP-FR. PMID- 1868720 TI - Contact dermatitis from geraniol in Bulgarian rose oil. PMID- 1868721 TI - Imidazolidinyl urea (Germall 115) should be patch tested in water. PMID- 1868722 TI - Bone-setter's herbs dermatitis in Hong Kong. PMID- 1868723 TI - Formaldehyde-induced anaphylaxis after dental treatment? PMID- 1868724 TI - Generalized dermatitis due to an osteosynthesis screw. PMID- 1868725 TI - Contact depigmentation by adhesive material of bindi. PMID- 1868726 TI - Allergic contact cheilitis from toothpastes. PMID- 1868727 TI - Contact dermatitis due to incense. PMID- 1868728 TI - Allergic reaction of the oral mucosa in a patient with a synthetic denture. PMID- 1868729 TI - Contact allergy to oil of turpentine: a 10-year retrospective view. Contact Dermatitis Research Group in Comecon Countries. PMID- 1868730 TI - Compositae dermatitis aggravated by eating lettuce. PMID- 1868731 TI - Oral contraceptives and neoplasia: an introduction. PMID- 1868732 TI - Oral contraceptives and neoplasia of the ovary. AB - Epidemiologic literature on oral contraceptives in relation to primary ovarian cancer is reviewed. Compared to women who have never used oral contraceptives, women who have ever taken oral contraceptives have about a 30% reduction in risk for epithelial ovarian cancer, and five or more years of use is associated with a 50% reduction in risk. The protective effect of oral contraceptives persists for ten or more years after use is discontinued, and becomes apparent several years after beginning use. Effects of oral contraceptives are similar for malignant and borderline malignant epithelial ovarian cancer. Reduced risks among oral contraceptive users have been observed for all major histologic subtypes of epithelial ovarian cancer, and for women from developed and developing countries. Risk estimates for epithelial ovarian cancer in relation to oral contraceptive use stratified by age at diagnosis or parity are not uniform across studies. No consistent protective effect is apparent for non-epithelial ovarian tumors or benign ovarian tumors, including teratomas and cystadenomas, although limited data are available on the relationship between oral contraceptives and these neoplasms. Several areas for future research are described. PMID- 1868733 TI - Oral contraceptives and neoplasia of the uterine corpus. AB - Effects of oral contraception on neoplasia of the uterine corpus are reviewed on the basis of epidemiologic studies reported to date. A duration-related protective effect against endometrial cancer occurs from use of combined oral contraceptives, those in which each active pill contains both estrogen and progestogen. The risk before age 60 years is reduced by about 38% with two years of use; use of combined OCs for 4, 8, and 12 years, respectively, confers an estimated 51%, 64%, and 70% reduction in endometrial cancer risk. The protective effect appears not to be diminished by discontinued use, even 15 or more years after stopping. Whether protection continues throughout the entire postmenopausal period, even in the presence of long-term hormone replacement therapy, remains to be seen. Use of combined OCs may protect against uterine leiomyomas ("fibroids"), but the evidence is not conclusive. The few findings about effects of oral contraception on the risk of adenomatous hyperplasia are of uncertain validity. Only one study, with few patients, has considered oral contraception in relation to uterine sarcomas. PMID- 1868734 TI - Oral contraceptives and cervical neoplasia. AB - Although initial studies examining the relationship of oral contraceptives to risk of cervical neoplasia were reassuring, more recent studies provide some evidence of a positive relationship, particularly for long-term usage. Results, however, are difficult to interpret, because of a variety of methodologic complexities, including potential sources of confounding and bias. Sexual behavior and Pap smear screening have been identified as important confounders, but in several well-controlled studies residual excess risks of nearly 2-fold persist for users of 5 or more years. A possible promotional effect of oral contraceptives is suggested by higher risks associated with recent usage. There also is some suggestion of a stronger effect for adenocarcinomas than for squamous cell tumors. A relationship is biologically possible, given findings of hormone receptors in cervical tissue and the fact that oral contraceptives have been found to induce cervical hyperplasia. In addition, oral contraceptives may induce proliferation of the human papillomaviruses, the leading suspect agent for cervical cancer. Although a number of lines of evidence support a relationship of oral contraceptives to cervical cancer risk, firm conclusions await the results of additional studies that specifically address some of the methodologic shortcomings of previous investigations. In particular, additional follow-up studies are needed to define the effect of oral contraceptives on the natural history of cervical lesions. PMID- 1868735 TI - Oral contraceptives and breast cancer: review of the epidemiologic literature. AB - Oral contraceptives have caused little or no overall increase in risk of breast cancer in women in developed countries, even in long-term users or after more than two decades since initial exposure. Limited evidence suggests a possible small increase in risk in users of oral contraceptives in developing countries, and further studies of breast cancer and oral contraceptives in low risk populations are warranted. Oral contraceptives may enhance risk of breast cancer in young women with a history of benign breast disease, and this possibility should also be investigated further. Multiple investigations have fairly consistently shown risk of breast cancer in women under age 45 years to be increased slightly in long-term users of oral contraceptives. Further studies should be conducted to elucidate the mechanism of this apparent phenomenon. PMID- 1868736 TI - Oral contraceptives and skin neoplasia. AB - A possible association between oral contraception and the development of cutaneous melanoma has been raised largely because of the hyperpigmentation of pregnancy and the effect pregnancy may have on the outcome of established disease. Present evidence suggests there is no causal link between oral contraceptive (OC) use and melanoma (or with benign melanocytic nevi), nor has a specific subgroup of women or subtype of melanoma been consistently implicated as being at increased risk of this disease due to use of OCs. PMID- 1868737 TI - The association of oral contraception with kidney cancer, colon cancer, gallbladder cancer (including extrahepatic bile duct cancer) and pituitary tumours. AB - This paper reviews the evidence for a relationship between oral contraceptive use and certain neoplasms: cancers of the kidney, colon and gallbladder (including the extrahepatic bile ducts) and tumours (benign or malignant) of the pituitary. Special reference is made to controlled epidemiological studies, both case control and cohort. There is no convincing evidence that oral contraceptive use is causally related, either negatively or positively, to any of the tumours studied. PMID- 1868738 TI - The WHO Collaborative Study of Neoplasia and Steroid Contraceptives: the influence of combined oral contraceptives on risk of neoplasms in developing and developed countries. AB - A hospital-based case-control study was conducted in eight developing and three developed countries to determine whether use of combined oral contraceptives alters risks of various cancers. An observed trend of increasing risk of invasive cervical cancer with duration of use may not represent a causal relationship and is the subject of further study. Decreased risks of ovarian and endometrial carcinomas in users likely indicate a protective effect of oral contraceptives, the degree of which was similar in developing and developed countries. A small increase in risk of breast cancer in recent and current users was found to be somewhat greater in developing than developed countries. Both causal and non causal interpretations of this finding have been offered. No associations were found between oral contraceptives and in situ cervical, hepatocellular, cholangio, or gallbladder carcinomas, or uterine sarcomas; but the power of this study to detect alterations in risks of these neoplasms in long-term users was low. PMID- 1868739 TI - Stress erosive gastritis. AB - Bleeding from stress erosive gastritis continues to be a potential problem in critically ill and injured patients, but fortunately its incidence has decreased dramatically over the last decade. The explanation for this circumstance is probably multifactorial, but clearly relates to our increased knowledge of its pathophysiology. This understanding has led to the routine use of measures to reduce intragastric acidity (luminal acid being a prerequisite for stress ulcer to occur), coupled with improved techniques for the treatment of shock and the accompanying gastric mucosal hypoperfusion (another prerequisite for the formation of stress ulcers). A number of measures have been used to lower intragastric acidity with H2 receptor blockers emerging as the agents of choice to accomplish this goal. In the unlikely event that bleeding occurs despite these prophylactic measures, aggressive medical management will result in cessation of hemorrhage in over 80% of patients. In those few individuals requiring surgery to control bleeding, no operation has emerged as the recognized procedure of choice. Thus, we believe that a conservative operative approach is indicated in this setting and recommend vagotomy and pyloroplasty with oversewing of the bleeding erosions as appropriate therapy for most patients requiring surgical intervention. PMID- 1868740 TI - Safety of epichlorhydrin-treated cornstarch powder for surgical gloves: relevance to epoxy-resin-sensitized persons. PMID- 1868741 TI - A dermatologic diary. Portrait of a practice. PMID- 1868742 TI - Lice infestation. PMID- 1868743 TI - Oral acyclovir for chickenpox. AB - We report on our experience with acyclovir (Zovirax) capsules for the symptomatic treatment of chickenpox in two children and an adult. PMID- 1868744 TI - Proliferating trichilemmal cyst in an organoid nevus. AB - An unusual tumor mass of the scalp found in an elderly woman is presented. This lesion had many features simulating a verrucous squamous cell carcinoma of the scalp. Pathologic findings eventually revealed the tumor mass to be a proliferating trichilemmal cyst. Differentiation between a benign and malignant process in these lesions can sometimes be difficult. Clinical as well as histopathologic evaluation is necessary to make an accurate diagnosis. PMID- 1868745 TI - Congenital giant pigmented nevus presenting in one identical twin. AB - A case of congenital giant pigmented nevus in only one of identical twins confirmed by results of DNA print marker testing is discussed. The benign lesion was removed by serial excision over a five-year period, with excellent results. Current concepts in pathogenesis and genetics are reviewed. We conclude that there is evidence for both genetic and nongenetic causes of congenital giant pigmented nevi. PMID- 1868746 TI - Intravascular papillary endothelial hyperplasia: a case report. AB - A case of intravascular papillary endothelial hyperplasia occurring in a thirty nine-year-old woman is described. Examination of an excisional biopsy specimen showed typical changes of intravascular papillary endothelial hyperplasia. Dermatologists should be aware of this benign vascular disorder, since it resembles a low-grade angiosarcoma. PMID- 1868747 TI - White forelock in Marfan's syndrome: an unusual association, with review of the literature. AB - The cutaneous expression of Marfan's syndrome is generally limited to striae distensae and a number of uncommon associations with other dermatologic disorders. To date, there have been no reported cases of hair or nail abnormalities accompanying this disorder. We describe a patient with Marfan's syndrome who presented with an acquired white forelock and we review the literature on the association of poliosis with various entities. PMID- 1868748 TI - Naftifine gel in the treatment of tinea pedis: two double-blind, multicenter studies. Naftifine Gel Study Group. AB - Three hundred and sixteen patients with a diagnosis of tinea pedis were evaluated in two multicenter, double-blind randomized studies. One hundred and fifty-nine patients applied naftifine gel 1 percent and 157 applied gel vehicle to affected areas twice daily for four weeks. At the end of treatment, the naftifine-treated groups had higher mycologic cure rates (66 percent and 63 percent) than the respective vehicle-treated groups (34 percent and 27 percent, p is less than 0.01 and p is less than 0.001). The rate of global improvement in patients' conditions and the reduction in the incidence and severity of most signs and symptoms was greater for naftifine-treated patients in both studies. The results of these studies indicate that twice-daily use of naftifine gel 1 percent is safe and significantly more effective than vehicle in the treatment of tinea pedis. PMID- 1868749 TI - Effects of aluminium salts on bone marrow chromosomes in rats in vivo. AB - Oral administration of aluminium sulphate to laboratory bred Rattus norvegicus for prolonged period induced dose dependent inhibition of dividing cells and an increase in chromosomal aberrations. The effect was not influenced by the duration of exposure. The toxicity of the two salts, aluminium sulphate and potassium aluminium sulphate, did not differ significantly at doses in which the metal contents were kept constant. PMID- 1868750 TI - Alpha/beta inversion of the Euplotes and Oxytricha tubulins. AB - Immunoblotting studies, using a polyclonal antibody specific for the alpha tubulin of ciliates and an anti-beta-tubulin monoclonal antibody, demonstrated that the tubulins of the ciliates Euplotes and Oxytricha show alpha/beta inversion although less accentuated than that observed in Paramecium and Tetrahymena. Results suggest that (a) the alpha/beta inversion may be a common characteristic within the Phylum Ciliophora; and (b) the electrophoretic behaviour of the alpha-tubulin may be useful for establishing evolutionary relatedness between the ciliates. PMID- 1868751 TI - Pulmonary clearance of 99mTc-DTPA. An index of alveolar epithelial permeability. PMID- 1868752 TI - Prophylaxis of postoperative thromboembolism. PMID- 1868753 TI - Prostaglandins in adipose tissue--with special reference to triglyceride metabolism. PMID- 1868754 TI - Insulin receptor binding and action in human adipocytes. A critical approach to methods, correlations with receptor binding to other cell types, and relations between insulin binding and action. AB - Since the beginning of the seventies, studies of the cellular mechanisms behind insulin resistance in man have included studies of insulin receptor binding and insulin action in isolated cells. In the first studies, only measurements of insulin binding to circulating blood cells (mononuclear cells and erythrocytes) were possible. In these studies it was thus necessary to anticipate that insulin binding to these cells was representative for binding to target cells for insulin (adipocytes, hepatocytes, muscle cells). Later, studies of the human adipocyte became available. In the isolated human adipocyte it was possible to measure both insulin binding and the action of insulin on glucose transport and on the intracellular glucose processing. Immediately, it was observed that receptor binding to the different cell types was not always comparable. Moreover, the relationship between fat cell insulin binding and action was not always straightforward. Because fat tissue is only responsible for a small fraction of total glucose uptake, it is not possible to know whether changes in insulin binding and action in this tissue is representative for changes in the total organism. In the present review these problems have been elucidated by studies of patients with insulin-dependent and non-insulin-dependent diabetes mellitus. In chapter one, the methods used in the clinical studies are reviewed. The precision (intraassay variability) and reproducibility (intraperson variability) has been measured for all insulin receptor assays. It was found that the earlier used assay for mononuclear cells was improved by using a pure monocyte assay, because precision as well as reproducibility was improved. On the other hand, these values were considerably poorer than those found for the other cell types. The precision was 0.09, 0.04, and 0.04 for monocytes, erythrocytes and adipocytes, respectively. The reproducibility was 0.19, 0.06 and 0.11. In order to be able to measure comparability between insulin binding to the above mentioned cell types and hepatocytes, methods for measurement of insulin binding to these cell types from swine have been developed. These studies showed that insulin binding to swine cells have many similarities to that of human cells whereas several dissimilarities were seen between insulin binding to rat and human cells. Thus, it is surmised that swine cells are more suitable than rat cells concerning insulin receptor binding and action studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1868755 TI - Calbindin-D of human small intestine and kidney. Purification, molecular properties and clinical significance. PMID- 1868756 TI - Ankylosing spondylitis--education, employment and invalidity. AB - Two hundred forty-eight patients suffering from ankylosing spondylitis (AS) completed a questionnaire about the social impact of the disease. Of the 84% who replied to the questions about employment status, 118 patients were employed full time. The ability to manage full-time employment was reduced in 41 patients. Eighty-five patients indicated that they had changed occupation or educational status as a cause of AS; 46 of these later experienced a more progressive course, which reduced their working capacity, and 31 retired as invalids. Despite the long-term morbidity with gradual loss of functional capacity, 85% were still able to work after more than 20 years of illness. If we pay more attention to initial symptoms related to AS, delay in the diagnosis of AS could be decreased and social instability avoided by guidance in education and light occupations. PMID- 1868757 TI - Fusidic acid for Behcet's colitis: a novel approach to T-cell specific immunosuppressive therapy. AB - A 33-year-old patient suffered from recurring Beh,cet's colitis despite treatment with corticosteroids and later cyclosporin. The patient was then successfully shifted from cyclosporin, a T-cell specific immunosuppressant, to fusidic acid treatment (500 mg t.i.d.). During fusidic acid treatment, he went into complete remission, and his prednisolone dose could be reduced from 30 to 5 mg/day. The case report substantiates recent in vitro data indicating that fusidic acid has a similar effect on T-cell function as cyclosporin. It is suggested that the effect of fusidic acid in other chronic immunoinflammatory diseases should be examined. PMID- 1868758 TI - Anxiety in voluntary HIV-antibody testing in pregnancy and its implications for preventive strategies. AB - During a three-month period in 1989, 820 pregnant women attending the antenatal clinic of the Aarhus University Hospital, Denmark, were offered a HIV-antibody test and asked to fill out an anonymous questionnaire about attitudes to HIV antibody testing; 779 (95.0%) agreed to do so. One hundred and fifty-six women (20.0% of the participants) had been tested on a previous occasion, and 629 (80.7%) accepted the present offer to be tested. The most prevalent reasons to decline testing were indifference to the epidemic (45.3% of those declining), refusal of (further) blood testing (34.7%) and fear of being infected (16.7%). Women who consented to be tested most often expressed fear of being infected (21.8%). Fear of registration worried less than 5% of study group members; only 1% declined to be tested because of such worry. The pattern of worries expressed by the pregnant women is interpreted as one of anxiety and, in part at least, perplexity as concerns how to take rational consequences of public messages about the HIV epidemic. It is suggested that future surveillance be based primarily on voluntary testing and, whenever needed and possible, supplied with anonymous unlinked testing of existing blood samples from groups and persons declining to be tested. Such surveillance strategies should be supported in individual patient contacts and public health educational campaigns underscoring the risk of heterosexual transmission of HIV and the need for repeated HIV-antibody testing of selected groups and individuals. PMID- 1868759 TI - [Altered monoamine metabolism in children with epilepsy]. AB - Tryptophan (Trp), 5-HTP, 5-HT, 5-HIAA, HVA, and MHPG in CSF and total Trp(T-Trp), free Trp(F-Trp) and serotonin in serum were determined in 80 children with epilepsy and also in a control group. It was found that Trp, 5-HT, 5-HIAA in CSF and F-Trp in blood decreased in children with epilepsy. But the decrease of F-Trp was not the main cause of decreased 5-HT metabolism, because the no positive correlations among the four substances were found. Each of them returned to normal levels after the treatment with phenytoin or valproate. 5-HT concentration was negatively correlated with the frequency of the epilepsy episodes. 5-HIAA and HVA levels were relatively higher in the epileptics with brain damage as with compared with those who had no brain damage. The MHPG level was higher in the patients simple partial seizures. Complex partial epileptics and those patients receiving antiepileptic drugs had a lower serum T-Trp level. T-Trp was negatively correlated with the serum valproate concentration. Both T-Trp and F-Trp levels decreased in the patients treated with phenytoin. PMID- 1868760 TI - [Appropriate dosage for maintaining effective serum level at night after taking one dose of magnesium valproate with separate measurements of serum Mg++ concentration]. AB - Gas chromatography was used for monitoring the serum valproate (VPA) levels in 33 epileptic adults. They were divided into 3 groups treated with Mg-VPA in dosage of 800 mg, 600 mg and 400mg respectively at 7 pm in an attempt to find out an appropriate dosage with which the effective serum level could be maintained in the night time for those patients with only nocturnal seizures. It was shown that from the beginning of the treatment with a dosing regimen of 800 mg as well as one week after the treatment with a dosing regimen of 600 mg at 7 pm each day, the serum VPA levels of more than 50 micrograms/ml throughout the night could be procurred. The serum Mg++ concentrations of 20 normal and 24 epileptic adults were measured with an atomic absorption spectrophotometer. The serum Mg++ concentrations were found to be within normal values (2.0-3.0 mg%). The differences of the data obtained from these measurements between the normal and epileptic adults as well as those before and after the treatment were statistically insignificant. PMID- 1868761 TI - [Comparison of three kinds of diagnostic criteria for neurosis]. AB - In order to compare utilizable value of three kinds of neurotic criteria, we made of diagnosis study of 139 neurotics by criteria of neurotic epidemiological investigation. The diagnostic criteria of Chinese expert Xu Youxin' for several types of neurosis and diagnosis criteria of the Chinese medical association for neurosis respectively. The result showed that consistent rate of diagnosis used three kinds of diagnostic criteria was 73.38 per cent. It suggested that criteria studied was acceptive, especially for neurosis diagnosis of the Chinese medical association. A further study is needed which is useful to improve its sensitivity and specifity for diagnosis of neurosis. PMID- 1868763 TI - [Clinical features and imaging findings of posterior cerebral artery infarction]. AB - The clinical features and imaging findings of posterior cerebral artery infarction (PCAI) in 18 cases verified by CT scan and/or MRI, DSA, SPECT were reported, and their interrelation were analyzed. It was found that the main clinical feature of PCAI was visual defect with amnesia syndrome, the lesion was predominant in the right hemisphere. In examining the structure and function of brain and vessels, each of CT, MRI, ECT and DSA had its own advantage and might complement the others, CT and MRI were better in displaying the structure of cerebral parenchyma than ECT and DSA, whereas, MRI was superior in distinguishing the lesions in deep white matter and subtentorial region. DSA was better than MRI and CT in displaying vascular structure, but was inferior in disclosing the occlusion of deep perforating branches or cortical arterioles. ECT, besides its ability to show the morphological changes of brain, was mainly used to disclose the functional changes of cerebral parenchyma, being a method to make early diagnosis for CVD. However, ECT was inferior than MRI and CT, in displaying lacunar infarction and lesions of brain-stem. PMID- 1868762 TI - [Effect of chronic antiplatelet treatment on platelet activating factor-induced platelet activity in stroke]. AB - The effect of chronic antiplatelet treatment on PAF--induced platelet aggregation, ATP--release, and cytoplasmic ionized calcium was studied in 20 acute ischemic stroke patients. Chronic antiplatelet treatment failed to suppress these PAF--induced platelet responses. We speculate that selective PAF antagonists may be useful in suppressing PAF--induced platelet activation, and thereby possibly improve the treatment of stroke. PMID- 1868764 TI - [Deleterious effects of calcium on the pathogenesis of ischemic brain damage]. AB - Using atomic absorption spectroscopy, we measured the regional distribution of tissue Ca++ contents of 24 rabbit brains sampled at 2,4,24 and 48 hours after the occlusion of Middle Cerebral Artery (MCAo) with accompanying histopathological examinations with 10 controls. At 2 hours after MCAo, brain tissue Ca++ concentration increased significantly (P less than 0.005) in the ischemic territory and increased further with times, far preceding the detectable pathological findings termed necrosis, which appeared at 12 hours after MCAo. It seems most probable that the deleterious effects of calcium play an important role in the pathogenesis of ischemic brain damage. PMID- 1868765 TI - [An analysis of regional cerebral blood flows (rCBF) in 120 patients with cerebrovascular disease]. AB - The rCBF in a group of 120 patients with cerebrovascular disease (CVD) diagnosed clinically as well as with CT scans and a group of 120 healthy subjects as controls was measured with the 133Xenon inhalation method. The result showed that the rCBF of the CVD group was significantly lower than that of the control group (P less than 0.01). The tally rate between the rCBF reduction areas and the lesion sites was 85 per cent. The areas of rCBF reduction measured with 133Xenon inhalation were larger than the extents of the lesions shown by CT scans in 47 cases of cerebral infarction. The rCBF reductions of bilateral cerebral hemispheres were found in 16 cases of cerebral infarction. The average hemispheric rCBF obviously decreased in 12 cases of multiple cerebral infarction with dementia, but showed no decrease of rCBF in 18 cases of small focal cerebral infarction. PMID- 1868766 TI - [Genetic factor in arteriosclerotic cerebral infarction]. AB - The family information from a group of patients with arteriosclerotic cerebral infarction and their matched controls is reported. The prevalence rate for arteriosclerotic cerebral infarction in the first-degree relatives of the cases was higher than that in the first-degree relatives of the controls. The heritability was estimated as 41 +/- 7%. No significant difference of heritability between males and females was found. The subgroup of less than 65 years of age was most closely associated with genetic factor in the three subgroups. These results suggest that genetic factor plays an important role in the etiology of arteriosclerotic cerebral infarction, especially in those with middle ages of onset. PMID- 1868767 TI - [Clinical significance of the changes in interpeak latency of brainstem auditory evoked potentials in patients with cerebellopontine angle tumors]. AB - Brainstem auditory evoked potentials (BAEP) were recorded and studied in 21 cases of cerebellopontine angle tumors (CPATs) identified with CT/operations. 111 healthy volunteers with 207 normal hearing ears served as controls. In the main the results indicated that there was an average significant increase of the III-V IPL in comparison with the III-V/I-III IPL on contralateral side. This finding suggested that as a result of its displacement of the brainstem to the opposite side, stem from the contralateral bony structure, when CPAT was suspected. Since individual variations exist especially in aged persons, interpretation in clinical practice had still to be individualized. PMID- 1868768 TI - [Crow-Fukase syndrome. A report of 2 cases]. AB - Two cases of crow-fukase syndrome were reported. Both cases showed the characteristic polyneuropathy, organomegaly, endocrinologic disturbances and skin involvement. There was no evident response to cortico--steroid therapy. PMID- 1868769 TI - [Topographic electroencephalography and its clinical application]. PMID- 1868770 TI - [Brain SPECT, CT and EEG in 45 cases of epilepsy during the intermission]. AB - The regional cerebral blood flows (rCBF) in 45 cases of epilepsy during the interictal period were determined with brain SPECT. The results were compared those obtained with CT scans and EEG. 48.89% of the SPECT were found to be abnormal while 8.98% were suspected to be abnormal; the 35.71% of the CT scans were found to be abnormal; 16 cases (39.02%) were found to show focal abnormalities in the EEG while 9 cases (21.95%) had epileptic form discharge. SPECT seemed to show more significance in discovering the abnormalities in the epileptics during the interictal period than CT or EEG. However, the combined use of these three methods of examinations would be of greater help for identifying the focal abnormalities in epilepsy. Two of the 22 cases with abnormal SPECT had increased rCBF, whereas the other 20 cases had decreased rCBF. Among the 22 cases of abnormal SPECT and 4 cases of suspected abnormalities, the locations of the lesions as indicated with SPECT in 3 cases were not consistent with those as with CT. There were 5 cases in which the SPECT findings were not consistent with those in EEG. PMID- 1868771 TI - Hypersensitivity pneumonitis. AB - Hypersensitivity pneumonitis or extrinsic allergic alveolitis is an immunologically mediated lung disease caused by repeated inhalations of organic antigens. The basic histologic lesion consists of a diffuse mononuclear cell infiltration of alveolar wall, alveoli, terminal bronchioles, and neighboring interstitium. The inflammation is often followed by granulomas, which then may progress to fibrosis. Although there is no single radiologic, physiologic, or immunologic test specific for hypersensitivity pneumonitis, the diagnosis can often be suspected on the basis of a compatible temporal relationship of pulmonary symptoms to the history of environmental or occupational exposure. Once the diagnosis is suspected, the presence of serum precipitating antibodies (IgG), suppressor cytotoxic lymphocytosis in bronchoalveolar lavage fluid, and granulomatous alveolitis in lung biopsy specimens are extremely helpful in confirming the diagnosis. In patients where the diagnosis is confirmed, avoidance of the causative antigen is the best therapy, although corticosteroids are used to suppress inflammation. Once the fibrosis is set in, the patient may gradually slide into respiratory failure, cor pulmonale, and death. PMID- 1868772 TI - [The possible participation of brain peptidases in regulating the memory function during aging]. PMID- 1868773 TI - [Reactive changes in the dendrites of cortical neurons]. PMID- 1868774 TI - [The specific effect of subthreshold concentrations of the smell of a cardiotropic substance]. PMID- 1868775 TI - Drug disposition in the mammalian eye and brain: a comparison of mechanisms. PMID- 1868776 TI - Metabolism of nicotine. PMID- 1868777 TI - Effect of microcirculatory heterogeneity on the determination of pharmacokinetic parameters: implications for risk assessment. PMID- 1868778 TI - Drug metabolism and liver disease in India. PMID- 1868779 TI - Mechanisms of metal transport across liver cell plasma membranes. AB - The liver's pivotal role in the homeostasis of essential trace metals and detoxification of exogenous metals is attributed to its ability to efficiently extract metals from plasma, metabolize, store, and redistribute them in various forms either into bile or back into the bloodstream. Bidirectional transport across the sinusoidal plasma membrane allows the liver to control plasma concentrations and therefore availability to other tissues. In contrast, transport across the canalicular membrane is largely, but not exclusively, unidirectional and is a major excretory pathway. Although each metal has relatively distinct hepatic transport characteristics, some generalizations can be made. First, movement of metals from plasma to bile follows primarily a transcellular route. The roles of the paracellular pathway and of ductular secretion appear minimal. Second, intracellular binding proteins and in particular metallothionein play only indirect roles in transmembrane flux. The amounts of metallothionein normally secreted into plasma and bile are quite small and cannot account for total metal efflux. Third, metals traverse liver cell plasma membranes largely by facilitated diffusion, and by fluid-phase, adsorptive, and receptor-mediated endocytosis/exocytosis. There is currently no evidence for primary active transport. Because of the high rate of hepatocellular membrane turnover, metal transport via endocytic vesicles probably makes a larger contribution than previously recognized. Finally, there is significant overlap in substrate specificity on the putative membrane carriers for the essential trace metals. For example, zinc and copper share many transport characteristics and apparently compete for at least one common transport pathway. Similarly, canalicular transport of five of the metals discussed in this overview (Cu, Zn, Cd, Hg, and Pb) is linked to biliary GSH excretion. These metals may be transported as GSH complexes by the canalicular glutathione transport system(s). Unfortunately, none of the putative membrane carrier proteins have been studied at the subcellular or molecular level. Our knowledge of their biochemical properties is rudimentary and rests almost entirely on indirect evidence obtained in vivo or in intact cell systems. The challenge for the future is to isolate and characterize these putative metal carriers, and to determine how they are functionally regulated. PMID- 1868780 TI - Analysis of organotin uptake in Escherichia coli K-12. AB - The effect of tributyltin chloride (TBT) was potentiated by the presence of Tris ions in the growth medium compared with phosphate ions. The growth of Escherichia coli in the presence of Tris ions was inhibited completely at a concentration of 25 microM TBT whereas 79% growth was recorded in the presence of phosphate ions. Tris ions caused more protein to be released into the medium than phosphate ions. However, apart from protein release the rate of organotin uptake was less in Tris than in phosphate ions. Phosphate ions may play a positive role in the active accumulation of organotin into E. coli cells by providing cellular energy. PMID- 1868781 TI - Laboratory toxicity of potential blackfly larvicides on some African fish species in the Onchocerciasis Control Programme area. AB - The Onchocerciasis Control Programme of the World Health Organization uses larvicides to fight against the aquatic stages of the vector Simulium damnosum s.l., and thereby interrupt transmission of the disease. Since the appearance of resistance to Abate and chlorphoxim in certain cytotypes of the vector, the efficacy of many possible replacement insecticides has been tested and the impact of the best of them (permethrin, cyphenothrin, pyraclofos, and carbosulfan) on the aquatic fauna evaluated. PMID- 1868782 TI - A comparative study of genotype sensitivity to acute toxic stress using clones of Daphnia magna straus. AB - The genetic typing of laboratory strains of Daphnia magna revealed that although there are genetic differences between different testing laboratory strains, most laboratories culture single genotypes as clones. A comparative study was made of the performance of five of the more common clones in terms of neonate mortality under acute exposure to nine toxic chemicals. The range in clonal EC50 response was from less than one to more than two orders of magnitude in terms of concentration. Surprisingly, there was little pattern in rank order of response of clones exposed to different toxicants, thus suggesting that genotype environment interactions were predominating. Nevertheless, it was suggested that specifying the genotype used in D. magna toxicity tests will result in increased test repeatability. Evidence indicating that culture environment may also significantly affect the performance of neonates in acute toxicity tests was also presented. PMID- 1868783 TI - Piperonyl butoxide as a tool in aquatic toxicological research with organophosphate insecticides. AB - Experiments were conducted to determine the effects of piperonyl butoxide, a synthetic methylenedioxyphenyl inhibitor of cytochrome(s) P450, on the toxicity of organophosphate insecticides to three cladoceran test species: Ceriodaphnia dubia. Daphnia magna, and Daphnia pulex. Coadministration of piperonyl butoxide effectively reduced the acute toxicity of four metabolically activated organophosphates (parathion, methyl parathion, diazinon, and malathion) and did not affect the toxicity of three organophosphates not requiring metabolic activation (dichlorvos, chlorfenvinphos, and mevinphos). These results indicate that piperonyl butoxide may be an effective tool in toxicological research focused upon identifying specific compounds responsible for toxicity in complex aqueous mixtures. PMID- 1868784 TI - Stress protein synthesis, a potential toxicity marker in Escherichia coli. AB - Various chemicals were tested in Escherichia coli for the ability to modify the cellular growth rate and to induce the synthesis of heat shock and stress proteins. The toxicity of chemicals as observed by modification of the growth rate depended on concentration and duration of treatment, except for thiram. In this last case, no modification was observed up to a concentration of 10 micrograms.ml-1. In contrast, all toxicants tested enhanced the synthesis of heat shock and stress proteins. The stress response was similar but not identical. Heat shock proteins and stress proteins appear to be a more sensitive toxicity marker than growth inhibition. Suggestions for the use of stress proteins as a practical bioassay are made. PMID- 1868785 TI - A comparative study of blood changes and brain acetylcholinesterase inhibition by monocrotophos and its analogues in rats. AB - The effects of monocrotophos and its newly synthesized analogues, RPR-II and RPR V, on hematology and blood chemistry 24 hr post-treatment were studied in rats given doses of 0.96, 1.23, and 3.0 mg/kg po, respectively. It was found that monocrotophos caused a significant increase in the mean WBC count. RPR-V, a significant decrease in hematocrit and RBC count, whereas RPR-II did not alter any hematological parameter. The activities of membrane-bound enzymes in serum were not significantly changed by all three compounds except for a statistically significant increase of 38% in SGOT activity by RPR-II. Only monocrotophos caused a significant inhibition of the brain acetylcholinesterase activity. In vitro studies with partially purified preparations of rat brain cholinesterase revealed that monocrotophos was the most potent anticholinesterase agent, followed by RPR II and RPR-V. All three compounds caused inhibition of rat brain cholinesterase by decreasing the Vmax and increasing the Km values, indicating a mixed type of inhibition. The two analogues appeared to be less neurotoxic than monocrotophos. PMID- 1868786 TI - Biodegradation potential of some micromycetes for pentachlorophenol. AB - A first screening was performed upon 100 strains of micromycetes cultivated on solid media (malt extract medium and mineral medium) with pentachlorophenol (PCP) (0.5 g/liter). Under these conditions, 50 strains gave a light blurring around the inoculation spot, indicating some PCP degradation. Later, 50 selected strains were cultivated in liquid synthetic medium with PCP (1 g/liter). After 6 days of cultivation, photodegradation occurred for 25%. On the whole, the consumption of PCP was 25% for Zygomycetes, 3% for yeasts, and 10-15% for Deuteromycetes, except 7% for Tuberculariales. It was shown that glucose repressed the PCP consumption. Among degrading fungi, some could grow with PCP when cultures were initiated with spores, others could not. A more detailed study was done with Phoma glomerata cultivated in liquid synthetic medium (PCP 100 mg/liter) in darkness or with light. Photodegradation increased up to 25% but abiotic degradation occurred also in darkness (8%). Consumption of PCP by Ph. glomerata was 27% after 2 days with light and was lower in darkness (19%). PMID- 1868787 TI - Acute toxicity tests using rotifers. IV. Effects of cyst age, temperature, and salinity on the sensitivity of Brachionus calyciflorus. AB - Several aspects of the response to toxicants using a standardized toxicity test with the freshwater rotifer Brachionus calyciflorus are described. Test animals are obtained by hatching cysts which produce animals of similar age and physiological condition. The acute toxicity of 28 compounds is described with 24 hr LC50's. The LC50's span five orders of magnitude, from silver at 0.008 mg.liter-1 to benzene at more than 1000 mg.liter-1. Control mortality in 84 tests averaged 2% with a standard deviation of 3%, indicating very consistent test sensitivity. Only once in 84 trials did a test fail because of excessive control mortality, yielding a failure rate of 1.2%. Cyst age from 0 to 18 months had no effect on the sensitivity of neonates to reference toxicants. Both high and low temperatures increased rotifer sensitivity to reference toxicants. Copper sensitivity was greater at 10, 25, and 30 degrees C compared with results at 20 degrees C. Likewise, sodium pentachlorophenol toxicity was greater at 10 and 30 degrees C compared with results at 20 degrees C. Survivorship curves at 25 degrees C of neonates under control conditions indicated that mortality begins at about 30 hr. This places a practical limit on toxicant exposure for the assay of 24 hr. B. calyciflorus cysts hatch at salinities up to 5 ppt and acute toxicity tests using pentachlorophenol at this salinity yielded LC50's about one-half those of standard freshwater. B. calyciflorus is preferred over Brachionus plicatilis for toxicity tests in salinities up to 5 ppt because it is consistently more sensitive. PMID- 1868788 TI - Altered performance of white sucker populations in the Manitouwadge chain of lakes is associated with changes in benthic macroinvertebrate communities as a result of copper and zinc contamination. AB - White sucker (Catostomus commersoni) collected from the Manitouwadge chain of lakes show a lower growth rate and fecundity in lakes contaminated with copper and zinc from a mixed metal mine. This study evaluated whether the changes in performance of the fish were related to direct impacts of the metals or indirect impacts associated with changes in food availability. Concentrations of metals in the water and sediment of lakes in the Manitouwadge chain were elevated, relative to reference sites. The concentrations of Cu and Zn in the digesta of white sucker were significantly higher, as were the levels of both Cu and Zn in liver, kidney, and gill tissue. Muscle and spleen levels of Cu and Zn were significantly lower or not different from controls. Tissue levels were within the homeostatic range for Cu and Zn. However, the total density of invertebrates varied from greater than 25,000 m-2 at control sites to less than 13,000 m-2 at contaminated sites, and the number of genera recorded was more than 50% lower in shallow water samples. There was almost a complete absence of several invertebrate taxa at contaminated sites, including Plecoptera, Ephemeroptera, Odonata, Trichoptera, Amphipoda, and Unionidae. Diptera accounted for 78 to 96% of the total numbers of individuals at metal-contaminated sites as compared with 40 to 75% at the control sites. An analysis of white sucker stomach contents showed that the contents closely reflected the benthic composition observed in the natural substrate. Changes in food availability and feeding activity were correlated with previous changes documented in the growth, fecundity, and lipid levels of white sucker. PMID- 1868789 TI - In vitro cytotoxicity studies with the fish hepatoma cell line, PLHC-1 (Poeciliopsis lucida). AB - The PLHC-1 fish hepatoma cell line (Poeciliopsis lucida) was used in the neutral red assay to evaluate the acute cytotoxicities of direct-acting (alkylbenzenes, phthalate diesters, and pesticides) and metabolism-mediated (benzo[a]pyrene) toxicants. The sequence of cytotoxic potencies for the alkylbenzenes and phthalate diesters appeared to be a direct function of their hydrophobicity (as described by logarithmic octanol/water partition coefficients). The organochlorine pesticides (alachlor and p,p'-methoxychlor) were more cytotoxic than the organophosphorus pesticides (EPN, diazinon, and malathion). The PLHC-1 cell line apparently maintained sufficient xenobiotic-metabolizing capacity, as the hepatoma cells were able to metabolize benzo[a]pyrene to cytotoxic intermediates. Xenobiotic-metabolizing capacity was temperature dependent, with enzymatic activity increasing as the temperature was increased from 28 to 34 to 37 degrees C, was inducible by Aroclor 1254 (a chemical inducer of cytochrome P450-dependent monooxygenase activity), and was reduced by EPN (an inhibitor of P450 activity). PMID- 1868790 TI - Flow cytometric DNA analysis of ducks accumulating 137Cs on a reactor reservoir. AB - The objective of this study was to detect red blood cell (rbc) DNA abnormalities in male, game-farm mallard ducks as they ranged freely and accumulated 137Cs (radiocesium) from an abandoned nuclear reactor cooling reservoir. Prior to release, the ducks were tamed to enable recapture at will. Flow cytometric measurements conducted at intervals during the first year of exposure yielded cell cycle percentages of DNA (G0/G1, S, G2 + M phases) of rbc, as well as coefficients of variation (CV) in the G0/G1 phase. DNA histograms of exposed ducks were compared with two sets of controls which were maintained 30 and 150 miles from the study site. 137Cs live wholebody burdens were also measured in these animals in a parallel kinetics study, and an approximate steady-state equilibrium was attained after about 8 months. DNA histograms from 2 of the 14 contaminated ducks revealed DNA aneuploid-like patterns after 9 months exposure. These two ducks were removed from the experiment at this time, and when sampled again 1 month later, one continued to exhibit DNA aneuploidy. None of the control DNA histograms demonstrated DNA aneuploid-like patterns. There were no significant differences in cell cycle percentages at any time point between control and exposed animals. A significant increase in CV was observed at 9 months exposure, but after removal of the two ducks with DNA aneuploidy, no significant difference was detected in the group monitored after 12 months exposure. An increased variation in the DNA and DNA aneuploidy could, therefore, be detected in duck rbc using flow cytometric analysis, with the onset of these effects being related to the attainment of maximal levels of 137Cs body burdens in the exposed animals. PMID- 1868791 TI - Mercury and selenium interaction: a review. AB - This paper reviews studies on mercury and selenium interaction. It includes the effects of selenium on mercury toxicity on the organism, organ/tissue, and subcellular levels. The paper also touches on possible mechanisms for the "protective action" of selenium against mercury toxicity and deals briefly with the synergism between the two elements. PMID- 1868792 TI - [The job market in health care: theoretical, conceptual and methodological aspects]. PMID- 1868793 TI - [The process of producing health services]. PMID- 1868794 TI - [The sociology of professions: a new approach]. PMID- 1868795 TI - [The work force in the health sector: theoretical elements and empirical findings]. PMID- 1868796 TI - [Medical education in the 1990's: optimism is not enough]. PMID- 1868797 TI - [The medical profession: representation, work and change]. PMID- 1868798 TI - [Education in public health in Brazil]. PMID- 1868799 TI - [Exchange and interinstitutional cooperation in the development of education and research in collective health: account of the Brazilian experience]. PMID- 1868800 TI - [Center for training and methodological development in the area of health (CEFYDEM)]. PMID- 1868801 TI - Prevalence of epilepsy in Rochester, Minnesota: 1940-1980. AB - The prevalence of epilepsy in Rochester, Minnesota has been determined for a specific date in each of 5 decennial census years. Individuals with a diagnosis of epilepsy (recurrent unprovoked seizures) who were known to have experienced a seizure or who had received antiepileptic medication in the preceding 5 years were considered active prevalence cases. By this definition, the age-adjusted prevalence per 1,000 population, increased steadily from 2.7 in 1940 to 6.8 in 1980. At each of five prevalence dates, for all prevalence cases, 60% had epilepsy manifest by partial seizures, and 75% had no known etiology. Prevalence was higher for males than females for all except the last prevalence day. After 1950, prevalence tended to increase with advancing age and was highest in the oldest age groups. On the average, the 1980 prevalence cases had epilepsy less than 10 years and greater than 50% had their first diagnosis in the first 20 years of life. PMID- 1868803 TI - Magnetic resonance imaging of intractable complex partial seizures: pathologic and electroencephalographic correlation. AB - Prior studies indicate variable usefulness of magnetic resonance imaging (MRI) in the evaluation of patients with complex partial seizures (CPS), but sensitivities as low as 12% have been reported. We analyzed the MRI examinations of 20 patients with medically refractory CPS who later underwent resection of the seizure focus proven by electroencephalography (EEG). MRI studies were correlated with surgical pathology in all patients. Eleven of the 20 CPS patients had mesial temporal sclerosis (MTS). Seven of the 11 (64%) exhibited an MRI abnormality at the site of the EEG-demonstrated histopathologic focus. MRI abnormalities included temporal lobe hypoplasia or atrophy (four patients), and increased signal intensity on long repetition time (TR) sequences (three patients). Four patients had no MRI abnormalities corresponding to the histopathologic focus. Nine of the 20 CPS patients had other abnormalities responsible for the seizures, including astrocytoma, cryptic vascular malformation, hamartoma, polymicrogyria, tuberous sclerosis (forme fruste), arachnoid cyst, and congenital hemiatrophy. No patient had normal MRI studies. Our single most useful MRI sequence was the coronal long TR/dual echo sequence, using cardiac gating and first-order gradient moment nulling to diminish flow-related artifacts that could hinder evaluation of medial temporal lobe structures. PMID- 1868802 TI - Magnetic resonance imaging and 31P spectroscopy of an interictal cortical spike focus in the rat. AB - Magnetic resonance imaging (MRI) has proven to be an effective noninvasive technique for identifying lesions in patients with temporal lobe epilepsy. It has also been suggested that MRI may be sensitive to transient functional or metabolic changes in brain tissue. Increased brain electrical activity as monitored by electroencephalography causes changes in cerebral metabolism that may be responsible for focal or regional alterations in signal in the MRI of some patients. To test this hypotheses, experimental interictal cortical foci were produced in rats by topical application of penicillin to one hemisphere of the brain. In vivo MRI and phosphorous-31 (31P) spectroscopy of the focal and contralateral hemifield were performed in a 30-cm bore 1.89-T Bruker MSL system. 31P spectroscopy revealed no quantifiable differences in pH or in phosphocreatinine and ATP levels between the focal area and the contralateral hemisphere or between experimental and saline-treated control animals. There were also no differences in proton MRI. Similar areas of prolonged T2 were found near the cortex and in the deeper parenchyma in 55% of the experimental animals and 50% of the controls. These results suggest that the electrical activity from an interictal cortical spike focus is not severe enough to perturb cerebral metabolism sufficiently to be detectable by 31P spectroscopy or proton imaging techniques. PMID- 1868804 TI - Magnetic resonance imaging evaluation of focal computed tomography abnormality in epilepsy. AB - Sixty-seven patients with epilepsy and isolated enhancing computed tomography (CT) scan lesion were studied with magnetic resonance imaging (MRI). Fifty-six patients (83.5%) had partial seizures and 11 (16.4%) had generalized seizures. Four distinct groups were identified by MRI: nonspecific 16 cases (23.8%), tuberculoma 38 cases (56.7%), cysticercosis 12 cases (17.9%), and abscess 1 case (1.4%). Patients in the non-specific group had lesions that were hyperintense on T2 images and hypointense or isointense on T1 images. Such lesions resolved completely in 5 months with serial MRIs while the patients were receiving antiepileptic drugs (AEDs). Virologic studies, including cerebrospinal fluid (CSF) serology, are suggested for patients with such MRI lesions. PMID- 1868805 TI - Seizures of fronto-orbital origin: a proven case. AB - Distinguishing characteristics of seizures of frontal origin have not been clearly delineated. We describe a case of seizures of proven fronto-orbital origin to provide further definition of characteristics of seizures arising in that lobe. A 36-year-old man had medically intractable seizures since age 8 years. Clinically the seizures were stereotyped, with cessation of activity followed by turning of head and body to the right and then by struggling, kicking, and vocalizations indicating fear. Total seizure duration was approximately 30 s, with an apparent abrupt return of consciousness. The interictal scalp EEGs were similar to those of primary generalized epilepsy, with bisynchronous though asymmetric epileptiform activity anteriorly. Ictal scalp recordings were not localizing. Recordings from bilateral frontal and temporal subdural electrodes showed an electrical focus in the right fronto-orbital region which was confirmed by electrocorticography (ECoG) at the time of craniotomy. The right fronto-orbital cortex was resected and on pathologic examination showed gliotic tissue and intracytoplasmic neuronal inclusions of periodic acid-Schiff (PAS)-positive granules consistent with lipofuscinosis. The patient has remained seizure-free for 6 years after operation. PMID- 1868806 TI - Paroxysmal kinesigenic choreoathetosis with abnormal electroencephalogram during attacks. AB - An 18-year-old man with paroxysmal kinesigenic choreoathetosis (PKC) showed rhythmic electroencephalographic (EEG) discharges of 5-Hz spikes over the entire scalp during episodes. The EEG findings in this case suggest that PKC may have an epileptogenic basis. PMID- 1868807 TI - Seizures in series: similarities between seizures of the west and Lennox-Gastaut syndromes. AB - We observed seizures resembling infantile spasms in patients with Lennox-Gastaut syndrome (LGS). Infantile spasms, the type of seizures that occurs in patients who have West syndrome, have been well characterized by video-EEG studies and typically occur as a series of sudden generalized flexor or extensor jerks. The seizure types that occur in LGS have not been as clearly delineated. Some patients with West syndrome (WS) in early infancy later develop LGS. Using intensive video-EEG monitoring, we evaluated 14 LGS patients who had seizures that occurred in series. Clinically, the seizures greatly resembled infantile spasms, and the ictal EEG changes were identical to those that occur with infantile spasms. These findings expand the number of features known to be shared by these two syndromes and strengthen the hypothesis that the two syndromes represent age-related manifestations of similar epileptogenic processes. PMID- 1868808 TI - Risk factors for febrile seizures in the People's Republic of China: a case control study. AB - A case control study was conducted to investigate the association of family history of febrile seizures (FS) and history of maternal, pregnancy and delivery, and postnatal factors with FS. Information was gathered by door-to-door survey in six major cities in the People's Republic of China. Factors present before the date of onset of FS were assessed in 182 subjects and in an equal number of controls matched for age, sex, and geographic area. The odds ratio for risk of FS in children with a family history of FS in a first-degree relative was 10.0 (confidence interval 2.7-58.6), confirming other observations that familial factors are an important predisposing characteristic for FS. Maternal acute respiratory infection during the first trimester of pregnancy was slightly more frequent in children with FS (odds ratio, 1.9 confidence interval 1.0-3.9). None of the other examined pregnancy or delivery factors was associated with an increased risk, suggesting that birth history is not an important factor predisposing to FS. PMID- 1868809 TI - A contribution to the genetics of febrile seizures: waking and sleep EEG in siblings. AB - Waking and sleep EEGs were recorded in 67 siblings of 52 patients with febrile seizures (FS). Epileptic activity was noted in at least 1 sibling for 28 of the 52 patients (53.8%). Epileptic discharges were noted in 33 (49.2%) of the 67 siblings. Thirty-two siblings had 3-4 Hz spike wave complexes, and 1 sibling had independent centrotemporal spike foci (rolandic foci). Epileptic activity was noted exclusively in the waking state in only 3%, in waking and sleep in 31.3%, and only in sleep in 14.9%. The greatest number of epileptic discharges occurred in waking during hyperventatilation (32.8%) and during stage C sleep (38.8%). In 5 photosensitive siblings, additional epileptic discharges were noted in sleep in 1 and in waking and sleep in 4. At least 1 sibling in 5 (55.6%) of 9 patients with complicated febrile seizures, in 23 (53.5%) of 43 patients with simple FS, and in 4 of 9 patients (44.4%) with later onset epileptic seizures had seizure discharges. At least 1 sibling in 24 of 43 patients (55.8%) with exclusively FS in 13 of 30 (43.3%) male patients and in 15 of 22 (68.2%) female patients had seizure discharges. Siblings aged 6-10 years had (66.7%) the highest rates of activation. Epileptic discharges were noted in 83.3% of siblings with seizures, but in only 45.9% of siblings without seizures. Seizure activity was recorded in 68.2% of siblings who had occipital 3-4-Hz theta-delta-activity but in only 13.0% of siblings without this pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868810 TI - Familial aggregation and severity of epilepsy. AB - Genetic models for complex diseases frequently assume that genetic factors play a greater role in severe forms than in mild forms of disease. This study examined familial aggregation of epilepsy in relation to two measures of severity: duration and remission. The study population comprised 358 offspring born in Rochester, MN, U.S.A., to parents with epilepsy who were diagnosed in Rochester between 1935 and 1979 and followed for greater than or equal to 5 years after the first seizure. Cox proportional hazards analysis was used to examine the effects of duration of the parent's epilepsy (less than 5 vs. greater than or equal to 5 years) and remission of the parent's epilepsy (greater than or equal to 5 years seizure-free) on risk of unprovoked seizures in offspring. The univariate rate ratio (RR) for parent's duration (long vs. short) was 1.1 (95% confidence interval 0.32-3.57). The RR for parent's remission was 2.5 (0.55-11.41), reflecting a higher risk for offspring of remitting parents, which was not statistically significant. Multivariate analysis was used to control for three other parental attributes associated with offspring seizure risk: sex, age at onset of seizures (less than 20 vs. greater than or equal to 20 years), and seizure type (absence vs. other). The RR for duration was not substantially changed in this analysis (1.2; 0.37-4.16). However, the RR for remission dropped to 1.2 (0.25-5.97), suggesting that the higher risk in offspring of remitting parents was largely explained by confounding with other factors that influence offspring seizure risk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868811 TI - Open, double-blind and long-term study of vigabatrin in chronic epilepsy. AB - We performed an open, double-blind, and long-term study of vigabatrin (gamma vinyl-GABA, GVG) in patients with treatment-resistant epilepsy who were receiving only one or at most two standard antiepileptic drugs (AEDs). The novel design included a parallel, double-blind, placebo-controlled phase that minimized the number of patients receiving placebo and allowed determination of the optimum dose of GVG for each patient before initiation of the double-blind phase. The study was divided into four phases. The first phase was a 6-week period of baseline observation. In the second phase, GVG was added openly to previous AEDs for 8 weeks. During the first 2 weeks of this phase, the dose of GVG was increased weekly and then, in the absence of adverse effects, was held constant for the next 6 weeks. At the end of this open phase, seizure frequency during the 6 weeks of constant treatment was compared with the baseline seizure frequency for each patient. Patients who experienced reduction greater than 50% in the frequency of any seizure type during the open phase were defined as responders. These responders were then entered into the third and double-blind phase, in which they were randomly allocated wither to continue active GVG treatment or placebo for 8 weeks. Thirty-three patients entered the study; 31 of 33 patients completed the initial open phase. Twenty patients achieved a reduction greater than or equal to 50% in the frequency of one or more seizure types and were eligible for the double-blind phase; 10 were randomized to continue GVG and 10 were randomized to placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868812 TI - Phenytoin-induced elevation of serum estradiol and reproductive dysfunction in men with epilepsy. AB - Reproductive and sexual dysfunction in men with epilepsy has been attributed to androgen deficiency. Low serum free testosterone (FT) levels occur in both hypogonadotropic and hypergonadotropic hypogonadism. Antiepileptic drugs (AEDs) have been implicated. Proposed mechanisms include induction of increased sex hormone binding globulin (SHBG) resulting in decreased FT, as well as dysfunction or premature aging of the hypothalamopituitary-gonadal axis. In an investigation comparing serum reproductive steroid levels among 20 men receiving phenytoin (PHT) monotherapy for complex partial seizures, 21 untreated men with complex partial seizures, and 20 age-matched normal controls, total estradiol levels were significantly higher in the PHT group (56.3 +/- 29.4 pg/ml, mean +/- SD) than in the untreated (32.4 +/- 27.4 pg/ml, p less than 0.01) and normal control (34.3 +/ 12.7 pg/ml, p less than 0.05) groups. The physiologically active non-SHBG-bound serum estradiol levels were also significantly higher in the medicated group (45.1 +/- 21.7 pg/ml) than in the untreated (29.9 +/- 17.2 pg/ml, p less than 0.01) and normal control (31.1 +/- 11.4 pg/ml, p = 0.05) groups. These findings suggest that PHT may lower FT by induction of aromatase, enhancing FT conversion to estradiol, as well as SHBG synthetase. Estradiol exerts a potent inhibitory influence on luteinizing hormone secretion and has been suggested to play a major role in negative feedback in men as well as women. Suppression of LH secretion results in hypogonadotropic hypogonadism. Chronically low FT leads to testicular failure and hypergonadotropic hypogonadism. Finally, estradiol has been shown to produce premature aging of the hypothalamic arcuate nucleus, which secretes gonadotropin-releasing hormone. PMID- 1868813 TI - Ralitoline: a reevaluation of anticonvulsant profile and determination of "active" plasma concentrations in comparison with prototype antiepileptic drugs in mice. AB - Ralitoline (RLT) is a new thiazolidinone derivative with potent anticonvulsant activity in different seizure models. During Phase I studies, RLT was well tolerated in human volunteers and showed linear pharmacokinetics in the dose range tested (up to 150 mg). Since RLT will soon be entering clinical Phase II studies, we were interested in obtaining predictive data for effective plasma concentrations in patients. For this purpose, the anticonvulsant potency of RLT was determined in four seizure models in mice, and plasma levels were measured at time of peak drug effect. The four models were the threshold for maximal (tonic extension) electroshock seizures (MES), the threshold for clonic seizures determined by i.v. infusion of pentylenetetrazol (PTZ), the traditional MES test with supramaximal (50 mA) stimulation, and generalized clonic seizures induced by s.c. administration of PTZ. Furthermore, median minimal "neurotoxic" doses (TD50s) were determined by the rotorod and chimney test for calculation of protective indices. All data obtained for RLT were compared with data obtained with standard antiepileptic drugs: phenobarbital, phenytoin, valproate, and diazepam. The onset of anticonvulsant action after i.p. injection of RLT was very rapid, and the peak drug effect was already obtained after 2 min. In the MES models, RLT was the most potent compound. "Active" plasma levels ranged from approximately 300 ng/ml in the MES threshold test to approximately 1,300 ng/ml in the MES test. RLT was also capable of increasing the PTZ threshold, whereas, possibly because of its short duration of action in mice, it was not very active in the s.c. PTZ seizure test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868814 TI - Effects of single- and multiday ozone exposures on respiratory function in active normal children. AB - Ventilatory function was measured twice daily on 46 healthy children aged 8-14 years on at least 7 days for each child during a 4-week period at a northwestern New Jersey residential summer camp in 1988. The highest 1-hr O3 concentration was 150 ppb, while the highest 12-hr H+ concentration (as H2SO4) was 18.6 micrograms/m3. The highest temperature-humidity index was 81 degrees F. The regressions of FVC, FEV1, FEF25-75, and PEFR on O3 in the hour preceding the afternoon function measurements yielded slopes essentially the same as those measured on other children at the same camp in 1984. Regressions of the changes in function between the late morning and late afternoon function measurements on average O3 concentration between them produced significant, but somewhat smaller effects, while regressions of morning function on O3 during the previous day indicated small but still significant effects. There were no significant correlations with other measured environmental variables including H+. Based on the results of this study and similar previous studies, we conclude that O3 exposures in ambient air produce greater lung function deficits in active young people in natural settings then does pure O3 in controlled chamber exposure studies because of: (1) longer exposures; (2) potentiation by other factors in the ambient exposures; (3) the persistence of effects from prior day's exposures; and (4) the persistence of a transient response associated with the daily peak of exposure. It follows that projections of likely effects in the real world from controlled chamber exposure studies should either have a large margin of safety, or the judgment of the extent of effects likely to occur among populations should be based directly on the effects observed in field studies. PMID- 1868815 TI - Reproductive performance in population exposed to pesticides in cotton fields in India. AB - Data on reproductive histories were collected from 1016 couples in which the males were directly exposed to pesticides. For comparison data were collected from 1020 couples who were not exposed to pesticides and belong to the same socioeconomic group and age range. Statistical analysis revealed a significant decrease in fertile males and a significant increase in abortions among the wives of these exposed males when compared to the control group. The frequency of live births decreased significantly and still births, neonatal deaths, and congenital defects showed a significant increase in the offspring of exposed males when compared to the offspring of control group. Smokers exposed to pesticides showed a higher effect than nonsmokers exposed to pesticides. Eighty percent males in the exposed group showed ill health effects such as severe giddiness, nervous, skin, and eye disorders. PMID- 1868816 TI - Lead and cadmium at very low doses affect in vitro immune response of human lymphocytes. AB - The effect of lead chloride and cadmium chloride on in vitro immunoglobulin (Ig) production by human lymphocytes was investigated. After 7 days in culture, lead added in the range of human exposure (207-1035 micrograms/liter) significantly enhanced Ig production either when cells were activated by pokeweed mitogen (PWM) or not. The effect was dose-dependent and was related to the Pb we measured in the extracellular medium and in the cells. Independently of the mitogen addition, about 2% of the Pb added was accumulated in the cells, most being associated with the nuclear fraction. Those findings suggest that the Pb effects could depend on its uptake and distribution in the cells. Cadmium added in the 50-500 nM range exhibited a dose-independent mitogenic activity in unstimulated cells, whereas the Ig secretion was not significantly affected by Cd when cells were PWM activated. A considerable intraindividual variability, however, was observed when blood donors were separately examined, with both an increase, a decrease, or no variation on Ig production. Furthermore, higher percentages of Cd were accumulated in the nuclear fraction, and lower in the cytosol and precipitate, in PWM-activated compared to resting lymphocytes. Genetic factors could be of importance for the observed variability of the immune response to cadmium, and we support the hypothesis that differences in the metallothionein (MT) inducibility could play a role. PMID- 1868817 TI - Mutagenic activity of photoreaction products formed from chlorinated ethenes and nitrogen dioxide. AB - The mutagenicity in Salmonella, strain TA 100, of photoreaction products from chlorinated alkenes and nitrogen dioxide, was studied after a mean reaction time of 40 min with UV-irradiation and an exposure time of 20 hr. Only vinyl chloride (monochloroethene) gave rise to significantly mutagenic photoreaction products. Of the other chloroethenes, 1,1-dichloroethene and tetrachloroethene, but not 1,2 dichloro- or trichloroethene, formed slightly mutagenic products. Bacteriotoxic effects occurred at low doses, especially with tri- and tetrachloroethene. PMID- 1868818 TI - An evaluation of experimental practices for abatement of residential lead-based paint: report on a pilot project. AB - In this pilot study, we prospectively evaluated experimental practices for abating lead-based paint in six dwellings. These experimental abatements were based upon a new approach to abatement which reflects current understanding of low-level lead toxicity in children and the role of lead-contaminated dust as an important contributor to children's total body burden. Our previous study of traditional abatement practices in Baltimore showed them to be inadequate for reducing lead in both house dust and children's blood. Our experimental abatements resulted in significant reductions in house dust-lead levels (PbD) which persisted during 6-9 months of followup. Geometric mean PbD at floors, window sills, and window wells were respectively 5.6, 49.6, and 316.7 mg/m2 at preabatement, and respectively 0.6, 4.4, and 10.8 mg/m2 at 6-9 months. Experimental abatements involved (1) treatment of lead-painted surfaces above and below 4 ft from the floor, including interior and exterior components of windows; (2) sealing or covering of wooden floors; (3) procedures for containment of dust during abatement; and (4) a final cleanup using a high-efficiency particle air (HEPA) vacuum. We recommend that more research be done to further evaluate and compare the long-term efficacy of these and other abatement methodologies. PMID- 1868819 TI - Monoamine turnover in the brain of mice during development of tolerance to the anticonvulsant effect of clonazepam. AB - Mice were treated for 14 days with clonazepam, 0.5 mg/kg i.p. twice daily, during which time partial tolerance to the anticonvulsant effect against pentetrazole developed. The development of tolerance was paralleled by a reduced turnover of noradrenaline in the whole brain, and of dopamine in the midbrain. The turnover of 5-HT was increased during the first week of treatment, but decreased thereafter. These changes in monoamine turnover, which are thought to be GABA mediated, are consistent with an increased seizure susceptibility, and may contribute to the development of tolerance to the anticonvulsant effect of benzodiazepines. PMID- 1868820 TI - Effects of seizures and carbamazepine on interictal spiking in amygdala kindled cats. AB - We examined the influence of seizures and carbamazepine (CBZ) on spiking rates in kindled cats. In the first experiment, spiking rates were measured before and after seizures, with and without CBZ. CBZ was administered immediately after seizures in order not to affect them. Spiking rates were measured over 9 h during the different sleep stages. In a second experiment, CBZ was administered before and after seizures so as to affect seizure strength and thus measure its effect on spiking. Results confirmed earlier findings of a large increase in spiking following a stage 6 seizure in fully kindled animals. We also established that: (1) repeated daily seizures caused a further increase in spiking until a ceiling was reached; (2) increased spiking was not a direct effect of postictal alterations in sleep stages; (3) CBZ, despite its effectiveness as an anticonvulsant, did not reduce spiking but rather increased it; (4) postictal increases in spiking were related to seizure 'strength'. These findings support the hypothesis that spiking rates are primarily influenced by seizure occurrence, as was found in patients with temporal lobe seizures, and that anticonvulsants act differently on seizures and spikes. This emphasizes the possibility of distinct pathophysiological mechanisms for interictal spikes and seizures. PMID- 1868821 TI - Effects of chronic treatment with haloperidol and methamphetamine on hippocampal kindled seizures in the cat. AB - We assessed the effects of chronic treatment with haloperidol (0.5-2 mg/kg/day, p.o., 17 days) and methamphetamine (1-2 mg/kg/day, p.o., 17 days; 4 mg/kg/day, p.o. 9 days) on hippocampal kindled seizures using a kindling procedure with low frequency (about 3 Hz) electrical stimulation in cats. The number of stimulating pulses required to trigger epileptic afterdischarge (pulse-number threshold, PNT) was considered an indicator of seizure threshold. Haloperidol, 0.5 and 1.0 mg/kg, reduced the duration of epileptic afterdischarge (afterdischarge duration, ADD) without affecting PNT, and 2.0 mg/kg strongly reduced PNT and ADD. Methamphetamine, 2.0 mg/kg, reduced PNT and ADD, and 4.0 mg/kg preferentially reduced PNT. The effects of the two drugs on hippocampal kindled seizures were found to be partially opposite to those on amygdala kindled seizures, suggesting the different response of these limbic structures to dopamine receptor manipulation. PMID- 1868822 TI - Comparison of gabapentin with other antiepileptic and GABAergic drugs. AB - The effect of the experimental antiepileptic drug gabapentin (1-(aminomethyl) cyclohexane acetic acid; GPT) on the feline trigeminal complex was compared with the effect of established antiepileptic drugs and with the effect of GABAA and GABAB agonists and antagonists. Intravenous injection of 10-60 mg/kg GPT depressed the descending periventricular facilitation of trigeminal nucleus neurons, as well as segmental excitatory mechanisms. On the other hand, GPT usually facilitated, but sometimes depressed, both segmental and periventricular inhibitory mechanisms. GPT thus resembled carbamazepine and phenytoin in its action on excitatory mechanisms and on segmental inhibition, but differed in its effect on inhibitory pathways descending from the reticular formation. In agreement with our observations, GPT has been found to be effective against partial and generalized tonic-clonic seizures, similar to the spectrum of activity of carbamazepine and phenytoin. The action of GPT in our model also resembled that of the GABAB agonist baclofen in its facilitation of reticular and segmental inhibitory mechanisms and its depression of segmental excitatory mechanisms, but differed in its effect on excitatory mechanisms descending from the reticular formation. GPT has also been reported to mimic GABAB receptor activation in other experiments but appeared to act by a GABA-receptor independent mechanism. PMID- 1868823 TI - Plasma uric acid in patients receiving anticonvulsant monotherapy. AB - In newly diagnosed adult patients with epilepsy followed prospectively on monotherapy, carbamazepine and phenytoin were associated with a fall in plasma uric acid, but sodium valproate and phenobarbitone were associated with a rise in plasma uric acid. The mechanisms and significance of these findings are discussed. PMID- 1868824 TI - The development of a seizure severity scale as an outcome measure in epilepsy. AB - In controlled trials of antiepileptic drugs (AEDs) seizure frequency is often the only variable considered. With little prospect of improving assessment of AEDs, using seizure counts as the only end-point, there is a need for the development of new outcome measures. Clinical experience indicates that seizure severity is equally important to the patient and, by preventing seizure spread, AEDs can influence seizure severity without necessarily reducing seizure frequency. A scale capable of measuring seizure severity and change of severity attributable to treatment could be a useful additional outcome measure. Such a scale should exhibit the basic properties of validity and reliability. An easily administrable 16-point scale, containing 2 subscales--perception of control and ictal/post ictal effects--has been developed. This scale has been tested on a patient population (n = 159) representative of that seen in trials of novel AEDs. Using standardised statistical methods, the scale has been shown to be both reliable and valid. PMID- 1868825 TI - A comprehensive community epilepsy programme: the Nakuru project. AB - The methodology of a programme of investigation of epilepsy carried out at a community health level in Nakuru district, Kenya, East Africa, and the characteristics of patients with tonic-clonic epilepsy in this community, are presented. The study identified a group of 302 patients with untreated generalised tonic-clonic seizures (with or without other seizure types) from the general population. Case finding was carried out using the key informant method over a 12-month period. The clinical characteristics of this cohort of patients, the majority of whom had never had previous contact with a formal medical system, is described. Most were young, living in a rural area, with a mean age of seizure onset of 14 years and a mean duration of seizures of 7 years. Thirty-eight per cent had a clinically evident focal disturbance associated with the tonic-clonic seizures. In 77% of the cases, no aetiology was established. Most cases had had a substantial number of seizures during the course of their condition and only about a third of the patients had less than 1 seizure a month in the previous year. Only 26% had ever had previous anti-epileptic drug treatment. In addition to the medical inquiry, psychological and sociological studies were also conducted and a prospective treatment programme was carried out. Throughout the study, strict definitions and standardised instruments were used, and the study was the result of a collaboration between local investigators, an international neurological team, the Kenyan Government agencies and the pharmaceutical industry. We consider this a model for community-based investigations for the management of epilepsy in developing countries. PMID- 1868826 TI - The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. AB - From the lysosomal cysteine proteinase cathepsin B, isolated from human liver in its two-chain form, monoclinic crystals were obtained which contain two molecules per asymmetric unit. The molecular structure was solved by a combination of Patterson search and heavy atom replacement methods (simultaneously with rat cathepsin B) and refined to a crystallographic R value of 0.164 using X-ray data to 2.15 A resolution. The overall folding pattern of cathepsin B and the arrangement of the active site residues are similar to the related cysteine proteinases papain, actinidin and calotropin DI. 166 alpha-carbon atoms out of 248 defined cathepsin B residues are topologically equivalent (with an r.m.s. deviation of 1.04 A) with alpha-carbon atoms of papain. However, several large insertion loops are accommodated on the molecular surface and modify its properties. The disulphide connectivities recently determined for bovine cathepsin B by chemical means were shown to be correct. Some of the primed subsites are occluded by a novel insertion loop, which seems to favour binding of peptide substrates with two residues carboxy-terminal to the scissile peptide bond; two histidine residues (His110 and His111) in this "occluding loop' provide positively charged anchors for the C-terminal carboxylate group of such polypeptide substrates. These structural features explain the well-known dipeptidyl carboxypeptidase activity of cathepsin B. The other subsites adjacent to the reactive site Cys29 are relatively similar to papain; Glu245 in the S2 subsite favours basic P2-side chains. The above mentioned histidine residues, but also the buried Glu171 might represent the group with a pKa of approximately 5.5 near the active site, which governs endo- and exopeptidase activity. The "occluding loop' does not allow cystatin-like protein inhibitors to bind to cathepsin B as they do to papain, consistent with the reduced affinity of these protein inhibitors for cathepsin B compared with the related plant enzymes. PMID- 1868827 TI - Chromophore motion during the bacteriorhodopsin photocycle: polarized absorption spectroscopy of bacteriorhodopsin and its M-state in bacteriorhodopsin crystals. AB - The three-dimensional crystallization of bacteriorhodopsin was systematically investigated and the needle-shaped crystal form analysed. In these crystals the M intermediate forms 10 times faster and decays 15 times more slowly than in purple membranes. Polarized absorption spectra of the crystals were measured in the dark and light adapted states. A slight decrease in the angle between the transition moment and the membrane plane was detected during dark adaptation. The crystallization of a mutated bacteriorhodopsin, in which the aspartic acid at residue 96 was replaced by asparagine, provided crystals with a long lived M intermediate. This allowed polarized absorption measurements of the M chromophore. The change in the polarization ratio upon formation of the M intermediate indicates an increase in the angle between the main transition dipole and the membrane plane by 2.2 degrees +/- 0.5, corresponding to a 0.5 A displacement of one end of the chromophore out of the membrane plane of the bacteriorhodopsin molecule. PMID- 1868828 TI - Two conserved domains in the NGF propeptide are necessary and sufficient for the biosynthesis of correctly processed and biologically active NGF. AB - The three members of the neurotrophin family (NGF, BDNF and NT-3) are synthesized as large precursor proteins which undergo proteolytic processing to yield biologically active, mature neurotrophic factors. We have used in vitro mutagenesis to examine the pro-region in the NGF precursor protein as a first step towards a general understanding of the role of propeptides in the biosynthesis of neurotrophins. Our results demonstrate that only two small domains within the NGF propeptide are required for the expression and secretion of properly processed and biologically active, recombinant mouse NGF in COS-7 cells. Domain I plays an important role in the expression of active NGF while domain II is involved in proteolytic processing. Both domains are partially conserved between the propeptides of NGF proteins isolated from different species as well as BDNF and NT-3. PMID- 1868829 TI - Functional adult acetylcholine receptor develops independently of motor innervation in Sol 8 mouse muscle cell line. AB - We have defined culture conditions, using a feeder layer of cells from the embryonic mesenchymal cell line, 10T1/2 and a serum-free medium, which allow cells from the mouse myogenic cell line Sol 8 to form contracting myotubes for two weeks. Under these culture conditions, Sol 8 myotubes undergo a maturation process characterized by a sequential expression of two phenotypes. An early phenotype is typified by the expression of the nicotinic acetylcholine receptor (AChR) gamma-subunit transcripts and the presence of low conductance ACh activated channels, typical of embryonic AChR. A late phenotype is characterized by the expression of AChR epsilon-subunit transcripts, the decreased accumulation of gamma-subunit transcripts and the appearance of high conductance ACh-activated channels, typical of adult AChR. These results indicate that the expression of functional adult type AChR does not require the presence of the motor nerve and therefore represents an intrinsic feature of the Sol 8 muscle cells. Chronic exposure of the cells to the voltage-sensitive Na+ channel blocking agent tetrodotoxin does not affect the appearance of the AChR epsilon-subunit transcripts but prevents the reduction of the steady-state level of the AChR gamma-subunit transcripts and yields a reduced proportion of the adult type channels. Thus, activity seems to facilitate the switch from the embryonic to the adult phenotype of the AChR protein. The Sol 8 cell system might be useful to analyse further the genetic and epigenetic regulation of muscle fibre maturation in mammals. PMID- 1868830 TI - Axonal transport of neuropeptide encoding mRNAs within the hypothalamo hypophyseal tract of rats. AB - Hypothalamic vasopressin and oxytocin transcripts have been detected in the posterior pituitary suggesting either transcription of the respective genes in pituicytes or axonal mRNA transport from the hypothalamus to the nerve terminals of the posterior pituitary. The concept of axonal mRNA transport is supported firstly, by Northern blot and in situ hybridization analysis indicating that vasopressin and oxytocin mRNAs are also present in the neural stalk; secondly, by intron analysis and transcription run on experiments demonstrating the absence of primary vasopressin and oxytocin transcripts in non-neuronal cells of the posterior pituitary; thirdly, by embryonic developmental studies showing that appearance of vasopressin transcripts in the hypothalamus and the pituitary anlage is correlated. Furthermore, during axonal transport the respective mRNAs are subject to specific modification at the poly(A) tails. PMID- 1868831 TI - Mechanisms of tandem duplication in the Duchenne muscular dystrophy gene include both homologous and nonhomologous intrachromosomal recombination. AB - Three tandem duplications were previously identified in patients with Duchenne muscular dystrophy and were shown in each case to have a subset of dystrophin gene exons duplicated. The origin of these duplications was traced to the single X chromosome of the maternal grandfathers, suggesting that an intrachromosomal event (unequal sister chromatid exchange) was involved in the formation of these duplications. In the present study, a DNA segment containing the duplication junction and the normal DNA that corresponds to both ends of the duplicated region have been cloned. Subsequent mapping studies confirmed the tandem arrangement (head to tail) of these duplications and revealed their sizes to be 130 kb, approximately 300 kb, and 35-80 kb, respectively. Sequence analysis of the duplication junctions showed that one duplication was due to homologous recombination between two repetitive elements (Alu sequences) and the other two were due to recombination between unrelated nonhomologous sequences. In the latter cases, the preferred cleavage sites of the eukaryotic type I and II DNA topoisomerases were found at the junctions of these duplications, suggesting a possible role of these enzymes in the chromatid exchange events. This study provides the first insight into the molecular basis of gene duplications formed through unequal sister chromatid exchange in humans. PMID- 1868833 TI - Genomic targets of the serendipity beta and delta zinc finger proteins and their respective DNA recognition sites. AB - The closely related Drosophila serendipity (sry) beta (beta) and delta (delta) Cys2-His2 zinc finger proteins show partly overlapping in vitro DNA binding specificities and distinct patterns of binding sites on polytene chromosomes. Using a newly developed procedure, we identified genomic DNA targets for these two proteins. Both the sry beta and delta proteins protect an 18-22 base region from DNase I digestion within each analysed genomic binding site, that includes a 13 bp consensus sequence. The consensus recognition sites sry beta 5' YCAGAGATGCGCA-3' and sry delta 5'-YTAGAGATGGRAA-3' thus differ by nucleotides at four out of 13 positions. They are determinant for specific binding of the sry beta and delta proteins, respectively, produced in Escherichia coli or present in Drosophila embryos. We further show that sry beta is the major (if not exclusive) Drosophila nuclear protein that specifically binds the 5'-CAGAGTGCGC-3' sequence. The identified sry beta genomic targets are all contained within single-copy DNA in euchromatic regions of the genome. Two out of the five characterized in detail map at cytological positions coincident with binding sites of the native sry beta protein on polytene chromosomes. PMID- 1868832 TI - Protein kinase C activation potently down-regulates the expression of its major substrate, 80K, in Swiss 3T3 cells. AB - The amino acid sequence of 80K, the major acidic protein kinase C (PKC) substrate of Swiss 3T3 fibroblasts, was deduced from a cDNA nucleotide sequence. Overall, 25% of the predicted amino acid sequence is supported by direct protein sequence data. Southern blot analysis suggests that the mouse genome contains a single copy of this gene. Two 80K mRNA species, a major band of 2.25 kb and a minor band of 3.9 kb, were detected by Northern blot analysis. Stimulation of PKC by biologically active phorbol esters, including phorbol-12, 13-dibutyrate (PDB), reduced the steady state level of 80K mRNA to 8.8% of control within 5-7 h. This effect was dose-dependent, and was abolished by prior depletion of PKC. The PDB induced down-regulation of 80K mRNA levels was transient, and recovery coincided with the disappearance of PKC activity. A similar transient decrease in 80K mRNA levels was also demonstrated in tertiary cultures of mouse embryo fibroblasts. The down-regulation of 80K mRNA levels was completely abolished by actinomycin D, cycloheximide or anisomycin if added up to 30 min after PDB addition. Since the rate of transcription of the 80K gene was unaltered by PDB treatment, we concluded that the PKC-induced down-regulation of 80K mRNA is mediated by a post transcriptional mechanism. In addition, PDB transiently decreased the level of 80K protein within 14-18 h, thus reflecting the effects of this phorbol ester on mRNA expression. PMID- 1868834 TI - Flexibility of the DNA enhances promoter affinity of Escherichia coli RNA polymerase. AB - Two types of mechanisms are discussed for the formation of active protein-DNA complexes: contacts with specific bases and interaction via specific DNA structures within the cognate DNA. We have studied the effect of a single nucleoside deletion on the interaction of Escherichia coli RNA polymerase with a strong promoter. This study reveals three patterns of interaction which can be attributed to different sites of the promoter, (i) direct base contact with the template strand in the '-35 region' (the 'recognition domain'), (ii) a DNA structure dependent interaction in the '-10 region' (the 'melting domain'), and (iii) an interaction which is based on a defined spatial relationship between the two domains of a promoter, namely the 'recognition domain' and the 'melting domain'. PMID- 1868835 TI - Identification of transcription factors required for the expression of mammalian U6 genes in vitro. AB - Transcription factors, required for the basal expression of the mouse U6 gene were identified in extracts from HeLa cells. This gene is transcribed at least four times more efficiently than its human counterpart in extracts from mouse or HeLa cells and hence provides an excellent in vitro system for the identification of transcription factors involved in the basal expression of mammalian U6 genes. At least four separate protein components were found to be required in addition to RNA polymerase III for correct synthesis of U6 RNA in vitro. These correspond to: (i) TFIIIB; (ii) a heat labile activity contained in a protein fraction enriched in TFIID; (iii) an, as yet, uncharacterized component contained in the flow-through upon rechromatography on phosphocellulose, and finally; (iv) a protein specifically binding to the mouse U6 gene promoter and transactivating its expression. Transcription factors IIIA and IIIC are not involved in mammalian U6 transcription in vitro. The U6-specific transcription factor has a molecular mass of approximately 90 +/- 10 kDa. It specifically binds to the U6 gene from bp -42 to -78 on the coding and from bp -37 to -79 on the non-coding strand thereby centrally encompassing the PSE motif of the mouse U6 promoter. The binding activity of this protein is correlated with the efficiency with which the U6 gene is transcribed in vitro, thereby indicating a crucial role of the PSE-binding protein for U6 transcription. PMID- 1868836 TI - Short leader sequences may be transferred from small RNAs to pre-mature mRNAs by trans-splicing in Euglena. AB - Very closely related short sequences are present at the 5' end of cytoplasmic mRNAs in Euglena as evidenced by comparison of cDNA sequences and hybrid-arrested translation experiments. By cloning Euglena gracilis nuclear DNA and isolating the rbcS gene (encoding the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase), we have shown that the short leader sequence does not flank the nuclear gene sequence. The leader sequences were found to constitute the 5' extremities of a family of small RNAs. Sequencing six members of this family revealed a striking similarity to vertebrate U snRNAs. We propose that a trans-splicing mechanism transfers the spliced leader (SL) sequence from these small RNAs (SL RNAs) to pre-mature mRNAs. Transfer of leader sequences to mRNAs by trans-splicing has been shown only in trypanosomes where cis-splicing is unknown, and in nematodes where not more than 10% of the mRNAs have leader sequences. Our results strongly suggest that Euglena is a unique organism in which both a widespread trans-splicing and a cis-splicing mechanism co-exist. PMID- 1868837 TI - Different effects of intron nucleotide composition and secondary structure on pre mRNA splicing in monocot and dicot plants. AB - We have found previously that the sequences important for recognition of pre-mRNA introns in dicot plants differ from those in the introns of vertebrates and yeast. Neither a conserved branch point nor a polypyrimidine tract, found in yeast and vertebrate introns respectively, are required. Instead, AU-rich sequences, a characteristic feature of dicot plant introns, are essential. Here we show that splicing in protoplasts of maize, a monocot, differs significantly from splicing in a dicot, Nicotiana plumbaginifolia. As in the case of dicots, a conserved branch point and a polypyrimidine tract are not required for intron processing in maize. However, unlike in dicots, AU-rich sequences are not essential, although their presence facilitates splicing if the splice site sequences are not optimal. The lack of an absolute requirement for AU-rich stretches in monocot introns in reflected in the occurrence of GC-rich introns in monocots but not in dicots. We also show that maize protoplasts are able to process a mammalian intron and short introns containing stem--loops, neither of which are spliced in N.plumbaginifolia protoplasts. The ability of maize, but not of N.plumbaginifolia to process stem--loop-containing or GC-rich introns suggests that one of the functions of AU-rich sequences during splicing of dicot plant pre mRNAs may be to minimize secondary structure within the intron. PMID- 1868838 TI - Activation of the nimA protein kinase plays a unique role during mitosis that cannot be bypassed by absence of the bimE checkpoint. AB - Mutation of nimA reversibly arrests cells in late G2 and nimA overexpression promotes premature mitosis. Here we demonstrate that the product of nimA (designated NIMA) has protein kinase activity that can phosphorylate beta-casein but not histone proteins. NIMA kinase activity is cell cycle regulated being 20 fold higher at mitosis when compared to S-phase arrested cells. NIMA activation is normally required in G2 to initiate chromosome condensation, to nucleate spindle pole body microtubules, and to allow an MPM-2 specific mitotic phosphorylation. All three of these mitotic events can occur in the absence of activated NIMA when the bimE gene is mutated (bimE7). However, the bimE7 mutation cannot completely bypass the requirement for nimA during mitosis as entry into mitosis in the absence of NIMA activation results in major mitotic defects that affect both the organization of the nuclear envelope and mitotic spindle. Thus, although nimA plays an essential but limited role during mitosis, mutation of nimA arrests all of mitosis. We therefore propose that mutation of nimA prevents mitotic initiation due to a checkpoint arrest that is negatively mediated by bimE. The checkpoint ensures that mitosis is not initiated until NIMA is mitotically activated. PMID- 1868839 TI - Activation of recA protein: the pitch of the helical complex with single-stranded DNA. AB - The complex of recA protein with single-stranded DNA in the presence of ATP is the active species in the three enzymatic activities of recA: the initiation of strand exchange, the hydrolysis of ATP and the cleavage of repressors. Here we find by cryo-electron microscopy of unstained and unfixed samples that the helical structure of the protein coat in this complex differs slightly but significantly from the structure in the complex with double-stranded DNA. We discuss how the larger pitch of the complex with single strands (100 +/- 2 A compared with 95 +/- 2 A with double strands) could contribute to its higher enzymatic activity. PMID- 1868840 TI - The replication termination signal terB of the Escherichia coli chromosome is a deletion hot spot. AB - Hybrids composed of phage M13, plasmid pBR322 and the termination signal of Escherichia coli chromosome replication terB were used to show that arrest of DNA synthesis creates a very efficient deletion hot spot. Up to 80% of deletions occurring in these hybrids had one deletion end-point at terB provided that (i) terB was oriented to arrest M13 and pBR322 leading strand synthesis; and (ii) the host cells contained the Tus protein necessary for arresting DNA synthesis at terB. The position of terB and the flanking sequences had little effect on deletion hot spot activity. About 90% of the deletions at terB ended 5-6 nucleotides in front of the major replication arrest site. We propose two models to account for deletion formation and speculate that many genome rearrangements may be due to the pausing of DNA replication. PMID- 1868841 TI - Molecular aspects of plastid envelope biochemistry. PMID- 1868842 TI - Glucose repression in Saccharomyces cerevisiae is directly associated with hexose phosphorylation by hexokinases PI and PII. AB - Genetic and biochemical analyses showed that hexokinase PII is mainly responsible for glucose repression in Saccharomyces cerevisiae, indicating a regulatory domain mediating glucose repression. Hexokinase PI/PII hybrids were constructed to identify the supposed regulatory domain and the repression behavior was observed in the respective transformants. The hybrid constructs allowed the identification of a domain (amino acid residues 102-246) associated with the fructose/glucose phosphorylation ratio. This ratio is characteristic of each isoenzyme, therefore this domain probably corresponds to the catalytic domain of hexokinases PI and PII. Glucose repression was associated with the C-terminal part of hexokinase PII, but only these constructs had high catalytic activity whereas opposite constructs were less active. Reduction of hexokinase PII activity by promoter deletion was inversely followed by a decrease in the glucose repression of invertase and maltase. These results did not support the hypothesis that a specific regulatory domain of hexokinase PII exists which is independent of the hexokinase PII catalytic domain. Gene disruptions of hexokinases further decreased repression when hexokinase PI was removed in addition to hexokinase PII. This proved that hexokinase PI also has some function in glucose repression. Stable hexokinase PI overproducers were nearly as effective for glucose repression as hexokinase PII. This showed that hexokinase PI is also capable of mediating glucose repression. All these results demonstrated that catalytically active hexokinases are indispensable for glucose repression. To rule out any further glycolytic reactions necessary for glucose repression, phosphoglucoisomerase activity was gradually reduced. Cells with residual phosphoglucoisomerase activities of less than 10% showed reduced growth on glucose. Even 1% residual activity was sufficient for normal glucose repression, which proved that additional glycolytic reactions are not necessary for glucose repression. To verify the role of hexokinases in glucose repression, the third glucose-phosphorylating enzyme, glucokinase, was stably overexpressed in a hexokinase PI/PII double-null mutant. No strong effect on glucose repression was observed, even in strains with 2.6 U/mg glucose-phosphorylating activity, which is threefold increased compared to wild-type cells. This result indicated that glucose repression is only associated with the activity of hexokinases PI and PII and not with that of glucokinase. PMID- 1868843 TI - Action of trypsin on glycinin. Mixed-type proteolysis and its kinetics; molecular mass of glycinin-T. AB - The formation of a relatively stable high-molecular-mass product on trypsin hydrolysis of glycinin (glycinin-T) is interpreted to be a result of 'zipper' proteolysis. Evidence of parallel one-by-one degradation of glycinin occurring after the formation of glycinin-T is presented. At a relatively low concentration of the substrate, the one-by-one proteolysis proceeds as a first-order reaction. A method of determination of the changes in the molecular mass of a protein during the mixed-type proteolysis and some other parameters of this process is developed on the basis of the analysis of the proteolysis kinetics. The value of the molecular mass of glycinin-T calculated by means of this method makes up 70% of the initial molecular mass and coincides with the result of direct determination by gradient gel electrophoresis. PMID- 1868844 TI - Differential interactions of estrogens and antiestrogens at the 17 beta-hydroxy or counterpart function with the estrogen receptor. AB - The action of diethylpyrocarbonate on lamb uterine estrogen receptor produced an homogeneous population of the receptor (approximately 55%) which still bound triarylethylene antiestrogens such as 4-hydroxytamoxifen with a high affinity but bound classical potent estrogens such as estradiol or diethylstilbestrol with a very low affinity. To specify the structural features of the ligands involved in the decrease of ligand affinity upon modification of the estrogen receptor, we determined the relative affinity constants of 17 steroidal estrogens or antiestrogens (deriving from estradiol by a 7 alpha- or 11 beta-substitution) and 14 nonsteroidal estrogens or antiestrogens (all including the 1,2-trans diphenylethylene structure of diethylstilbestrol) for native and diethylpyrocarbonate-modified estrogen receptors. Then the ratio of the relative affinity constant for the native receptor to that for the modified receptor (rho) was calculated for each ligand, to compare the variation in the affinity of the ligand upon modification of the receptor to that of 4-hydroxytamoxifen (rho = 1). The results showed that the strong decrease of ligand affinity upon modification of the receptor displayed by classical estrogens (rho greater than or equal to 200) is strictly dependent on the presence of the 17 beta-hydroxyl group in steroidal compounds or its alpha-4- and beta-4-counterparts in diethylstilbestrol related compounds. However, for the 7 alpha- or 11 beta-derivatives of estradiol displaying potent antiestrogenic properties, the relative decrease in affinity was much more limited (rho less than or equal to 19). For 11 beta-derivatives displaying a relative estrogenic activity weaker than that of estradiol itself, an average decrease in affinity was observed (23 less than or equal to rho less than or equal to 62). With the diethylstilbestrol-related compounds, bearing or not the alpha-4-hydroxyl and/or the beta-4-hydroxy functions and showing either weak relative estrogenic or antiestrogenic properties, the relative variation in affinity was weak (0.6 less than or equal to rho less than or equal to 24). These results indicate that the interaction of 7 alpha- or 11 beta-substituted steroidal antiestrogens and of 1,2-trans-diphenylethylene or triphenylethylene derivatives, displaying either weak relative estrogenic or antiestrogenic properties with the receptor, differs at the 17 beta-hydroxy or at the alpha-4 /beta-4-hydroxy functions from that of potent estrogens. They suggest that the strong decrease in the relative affinity of ligands upon receptor modification may reflect the high efficiency of the ligands to activate the receptor properly.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1868845 TI - Assignment of the five disulfide bridges in an alpha-amylase inhibitor from wheat kernel by fast-atom-bombardment mass spectrometry and Edman degradation. AB - The assignment of the five disulfide bridges in an alpha-amylase monomeric inhibitor from wheat kernel (coded 0.28) was achieved by combining fast-atom bombardment mass spectrometry (FAB-MS) and automatic sequencing based on Edman degradation. Direct FAB-MS analysis of the native and reduced enzymatic digests of the protein allowed the assignment of three disulfide bridges out of five, including those involving two adjacent cysteine residues. The remaining two disulfide bridges were assigned by sequencing automatically the peptide clusters purified from the tryptic digest of the native protein. PMID- 1868846 TI - Two-dimensional 1H-NMR studies of phospholipase-A2-inhibitor complexes bound to a micellar lipid-water interface. AB - One- and two-dimensional NMR studies were performed on the complexes of porcine pancreatic phospholipase A2 with substrate analogs bound to a micellar lipid water interface of fully deuterated dodecylphosphocholine. The interactions between the inhibitor and the enzyme were localized by comparison of the two dimensional NOE spectra recorded for the enzyme-inhibitor complex using both protonated and selectively deuterated inhibitors. These experiments led us to the following conclusions for the phospholipase-A2-micelle complex: (i) the 38-kDa phospholipase A2 complex gives NMR spectra with relatively narrow lines, which is indicative of high mobility of the enzyme; (ii) the residues Ala1, Trp3, Phe63 and Tyr69 located in the interface recognition site, as well as Phe22, Tyr75, Phe106 and Tyr111 are involved in the micelle-binding process; (iii) when present on the micelle, phospholipase A2 is stereospecific for the inhibitor binding; (iv) the inhibitor, (R)-dodecyl-2-aminohexanol-1-phosphoglycol, binds stoichiometrically to phospholipase A2 with high affinity (Kd less than or equal to 10 microM); (v) the inhibitor binds in the active site of the enzyme, which is evidenced by large chemical-shift differences for Phe5, Ile9, Phe22, His48, Tyr52 and Phe106; (vi) the acyl chain of the inhibitor makes hydrophobic contacts (less than 0.4 nm) near Phe5, Ile9, Phe22 and Phe106. Comparison of our results on the enzyme-inhibitor-micelle ternary complex with the crystal structure of the enzyme inhibitor complex [Thunnissen, M. M. G. M., AB, E., Kalk, K. H., Drenth, J., Dijkstra, B. W., Kuipers, O. P., Dijkman, R., de Haas, G. H. & Verheij, H. M. (1990) Nature 347, 689-691] shows that the mode of inhibitor binding is similar. PMID- 1868847 TI - On the importance of the support material for enzymatic synthesis in organic media. Support effects at controlled water activity. AB - Enzymes were deposited on different porous support materials and these preparations were used to catalyze reactions in organic media. Reactions were carried out at specific water activities, achieved by equilibrating both the enzyme preparation and the substrate solution at the desired water activity before mixing them and thereby starting the reactions. The reaction rates obtained at the same water activity with different supports differed greatly, indicating a direct influence of the support on the enzyme. For horse liver alcohol dehydrogenase, Celite was the best support, and the reaction rate increased with increasing water activity. In the alpha-chymotrypsin-catalyzed alcoholysis of N-acetyl-L-phenylalanine ethyl ester with 1-butanol, high rates were again obtained with Celite, but with this support only about one third of the ethyl ester was converted to butyl ester, the rest was hydrolyzed. With the polyamide support, Accurel PA6, alcoholysis was the dominating reaction, and by using a low water activity (0.33), hydrolysis was completely suppressed while still maintaining a high alcoholysis activity. Controlled pore glass (CPG), derivatized with either hexyl or glucosyl groups, had quite different properties as enzyme supports. For horse liver alcohol dehydrogenase, glucose-CPG was a much better support than hexyl-CPG, and in the alpha-chymotrypsin-catalyzed reactions, glucose-CPG favored hydrolysis, and hexyl-CPG alcoholysis, at water activities exceeding 0.8. The results are discussed considering the absorption of water on the enzymes, on the supports and the solubility of water in the reaction media; all these parameters were measured separately. PMID- 1868849 TI - Peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F cannot release glycans with fucose attached alpha 1----3 to the asparagine-linked N acetylglucosamine residue. AB - The ability of peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F (PNGase F) from Flavobacterium meningosepticum and PNGase A from sweet almonds to deglycosylate N-glycopeptides and N-glycoproteins from plants was compared. Bromelain glycopeptide and horseradish peroxidase-C glycoprotein, which contain xylose linked beta 1----2 to beta-mannose and fucose linked alpha 1----3 to the innermost N-acetylglucosamine, were used as substrates. In contrast to PNGase A, the enzyme from F. meningosepticum did not act upon these substrates even at concentrations 100-fold higher than required for complete deglycosylation of commonly used standard substrates. After removal of alpha 1----3-linked fucose from the plant glycopeptide and glycoprotein by mild acid hydrolysis, they were readily degraded by PNGase F at moderate enzyme concentrations. Hence we conclude that alpha 1----3 fucosylation of the inner N-acetylglucosamine impedes the enzymatic action of PNGase F. Knowledge of this limitation of the deglycosylation potential of PNGase F may turn it from a pitfall into a useful experimental tool. PMID- 1868848 TI - The specificity of chymotrypsin. A statistical analysis of hydrolysis data. AB - From the literature we collected all available quantitative data on the chymotrypsin-catalyzed hydrolysis of series of amino acid and peptide substrates. Utilizing this data base, we performed calculations on their quantitative structure/activity relationship (QSAR). The substrates were considered to be composed of fragments; log(kcat/Km) values for the substrates resulted from additive contributions of their fragments. Despite the fact that the kinetic constants in the data base were determined by different authors under various reaction conditions, the data are well described by the simple additivity model. Obviously, the intrinsic specificity of chymotrypsin dominates the influence of varying reaction conditions. PMID- 1868850 TI - Selective 13C-labelling of cyclosporin A. AB - Cyclosporin A is biosynthetically labelled with 13C by growing an overproducing strain of Tolypocladium inflatum on minimal media containing either [1-13C]-, [2 13C]-, [3-13C]- or [6-13C]glucose as the only carbon source. NMR analysis of the 13C-labelled peptide showed a labelling pattern in which 13C occurs at specific sites. These can be predicted by consideration of the relevant biosynthetic pathways. Quantitation of the site-specific enrichments revealed that the 13C label incorporation is efficient and selective. Metabolic fluxes through alternative pathways can also be estimated from these results. Isotopically labelled peptides will be a very useful tool for the study of molecular interactions with their receptors. PMID- 1868851 TI - Acid-base properties of nucleosides and nucleotides as a function of concentration. Comparison of the proton affinity of the nucleic base residues in the monomeric and self-associated, oligomeric 5'-triphosphates of inosine (ITP), guanosine (GTP), and adenosine (ATP). AB - The acid-base properties of the nucleic base residues of ITP, GTP, and ATP, and for comparison also as far as possible of the corresponding nucleosides, were studied in dependence on their concentration, i.e. on the effect of self association. From the dependence between the 1H-NMR chemical shifts of H-2 (where applicable), H-8, and H-1', and the pD of the solutions, the acidity constants for the deprotonation of the D+(N-7) site in D2(ITP)2-, D2(GTP)2-, D(Ino)+, and D(Guo)+, and of the D+(N-1) site in D2(ATP)2- and D(Ado)+ were calculated. Chemical shift/pD profiles for a whole series of varying concentrations of the nucleic base derivatives (= N) were constructed, including those for infinite dilution (delta o), which give the acidity constant for the monomeric N, and for infinitely concentrated solutions (delta infinity), which give the acidity constant of an N in an infinitely long stack. The acidity constants determined from the delta o/pD plots are in excellent agreement with the pKa values measured by potentiometric pH titrations of highly diluted solutions of N. The effects of self-association are striking; e.g. the pKa value of the D+(N-7) site in D2(GTP)2 is lowered by about 1 (as calculated from the delta o/pD and delta infinity/pD profiles), while the pKa value of the D+(N-1) site in D2(ATP)2- is increased by approximately 0.3; i.e. in the first case deprotonation is facilitated and in the second it is inhibited. The increasing inhibition of the H+(N-1) deprotonation with an increasing ATP concentration is due to the high stability of the dimeric [H2(ATP)]2(4-) stack for which the intermolecular H+(N-1)/gamma-P(OH)(O)2- ion pairs between the two ATP molecules are crucial. In those cases where no other significant interaction but aromatic-ring stacking in the self-association process occurs, the release of protons from protonated nitrogen-ring sites is facilitated with increasing stacking; this holds not only for D2(GTP)2- as indicated above, but also for D2(ITP)2-, D(Ino)+, and D(Ado)+. The latter example especially suggests that the situation for the D2(ATP)2- system is exceptional. Some consequences of the considered acid-base properties for biological systems are indicated. PMID- 1868852 TI - Characterization and purification of the fusicoccin-binding complex from plasma membranes of Commelina communis. AB - The fungal phytotoxin fusicoccin binds with high affinity to plasma membranes of the monocotyledonous plant, Commelina communis L. The sites bind the toxin with an apparent Kd of 5.2 nM and a pH optimum of 6.0. They occur at a level of approximately 6-8 pmol/mg plasma membrane protein. Photoaffinity labeling with the biologically active fusicoccin derivative 9'-nor-8'-(4-azido[3,5-3H]benzoyl) diaminoethylfusicoccin identified a polypeptide of 31.5 kDa on SDS/PAGE which was strongly labeled. A second 32.5-kDa band was also consistently labeled, although not to the same extent. The binding sites were solubilized in functional form and a purification scheme was developed based on affinity and ion-exchange procedures. The purified fraction contains two polypeptides of apparent molecular masses of 30.5 kDa and 31.6 kDa. A detailed molecular analysis of the fusicoccin binding complex is now possible. PMID- 1868853 TI - Characterization of a cDNA clone encoding molluscan insulin-related peptide II of Lymnaea stagnalis. AB - A cDNA clone encoding molluscan insulin-related peptide (MIP) II was isolated from a cDNA library of the central nervous system (CNS) of the freshwater snail, Lymnaea stagnalis, using a heterologous screening with a previously identified MIP cDNA (renamed MIP-I cDNA). The MIP-II cDNA encodes a preprohormone resembling the organization of preproinsulin, with a putative signal sequence, and A and B chains; however, in this case connected by two distinct C peptides, C alpha and C beta, instead of a single C peptide, a phenomenon which represents a new development in the prohormone organization of peptides belonging to the insulin superfamily. The A and B chains of MIP II and I differ remarkably in primary structure; in contrast, the C alpha peptide domains are fully identical. MIP II has only limited sequence similarity with insulins and related peptides. Both MIP II and I exhibit structural features, which make them a unique class of the insulin superfamily. The MIP I and II genes are expressed in a single type of neuron: the growth-controlling neuroendocrine light green cells of the Lymnaea CNS. PMID- 1868854 TI - On the role of polysialoglycosphingolipids as tetanus toxin receptors. A study with lipid monolayers. AB - Lipid monolayers of different compositions were used to study the interaction of tetanus toxin with membrane lipids and to evaluate the role of polysialoglycosphingolipids as membrane receptors. At neutral pH, the toxin binds to dioleoylglycerophosphocholine monolayers and inserts into the phospholipid layer. This effect is potentiated by acidic phospholipids without an apparent preference for a single class of phospholipids. Polysialoglycosphingolipids further increase the fixation and penetration of tetanus toxin in lipid monolayers, but no specific requirement for a particular ganglioside was identified. The ganglioside effect is abolished in the presence of other nervous tissue lipids: cerebrosides and glycosphingolipid sulfates are partially responsible for this effect. The penetration of tetanus toxin in the lipid monolayer is pH dependent. It increases with lowering pH, it is facilitated by acidic phospholipids and by glycosphingolipid sulfates and it is mediated both by hydrophobic and electrostatic interactions as deduced from an analysis of the effect of ionic strength. Fragment B of tetanus toxin the low-pH-driven lipid interaction of the toxin. On the basis of the present findings, the possible role of polysialoglycosphingolipids in the neurospecific binding of tetanus toxin is discussed. PMID- 1868855 TI - Regulation of smooth-muscle myosin-light-chain kinase. Steady-state kinetic studies of the reaction mechanism. AB - The kinetic mechanism of turkey gizzard smooth muscle myosin-light-chain kinase was investigated using the isolated 20-kDa light chain of myosin as substrate. The kinetic and product inhibition patterns of the forward reaction indicated an ordered sequential mechanism in which MgATP bound first, ADP was released last. The order of substrate binding and product release was confirmed independently by competitive, dead-end inhibition patterns obtained using the non-hydrolizable ATP analog adenosine 5'-[beta,gamma-imido]triphosphate. The mechanism was also characterized by a relatively strong product inhibition by ADP and a weak one by phosphorylated 20-kDa light-chain myosin, in addition to a significant inhibition by the latter product via a formation of a dead-end complex. [gamma-32P]ATP in equilibrium with [32P]phosphorylated light chain isotope-exchange data were consistent with the deduced mechanism and with the presence of the latter dead end complex. PMID- 1868856 TI - GDP-fucose: beta-N-acetylglucosamine (Fuc to (Fuc alpha 1----6GlcNAc)-Asn peptide)alpha 1----3-fucosyltransferase activity in honeybee (Apis mellifica) venom glands. The difucosylation of asparagine-bound N-acetylglucosamine. AB - Incubation of honeybee (Apis mellifica) venom-gland extracts with GDP-[14C]fucose and GlcNAc beta 1----2Man alpha 1----6(GlcNAc beta 1----2Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAc beta 1----N-Asn peptide(NAc) gave a labeled product in 40% yield. Analysis by 500-MHz 1H-NMR spectroscopy indicated the transferred fucose-(Fuc) residue to be alpha 1----3 linked to the Asn-bound GlcNAc. Further proof was provided by one-dimensional and two-dimensional 1H-NMR analysis of the incubation mixture, after incubation with beta-N-acetylhexosaminidase. The established carbohydrate structure (formula; see text) proves the existence of a novel alpha 1----3-fucosyltransferase with the ability to effect difucosylation of the Asn-bound GlcNAc in N-glycans. PMID- 1868857 TI - Beta-2-microglobulin levels in the cerebrospinal fluid: their value as a disease marker. A review of the recent literature. AB - The usefulness of measuring beta 2-microglobulin levels in the cerebrospinal fluid (CSF) in neurological diseases is discussed and the relevant literature is reviewed in this article. An elevation of this protein in the CSF is particularly indicative of disease activity in multiple sclerosis, neuro-Behcet's disease, sarcoidosis, acquired immunodeficiency syndrome-dementia complex and meningeal metastasis of malignant tumors, especially the meningeal dissemination of acute leukemia and malignant lymphoma. PMID- 1868858 TI - Isolated oculomotor nerve palsy due to dural cavernous sinus fistula. AB - Two patients with a dural carotid-cavernous sinus fistula presented with unilateral oculomotor nerve palsies without signs of ocular congestion or proptosis. According to this, dural carotid-cavernous sinus fistula should be included in the differential diagnosis of any case of painful ophthalmoplegia, even in the absence of other ocular signs. PMID- 1868859 TI - Long-term EEG monitoring in uremic children on chronic dialysis treatment. AB - Even in the absence of clinically apparent seizures, patients undergoing chronic dialysis often exhibit abnormal EEG activity, which is usually attributed to the type of dialysis or to the dysequilibrium syndrome. To find out whether these abnormalities occurred only during dialysis sessions, 10 children with end-stage renal failure undergoing chronic dialysis were continuously monitored for 52 h during dialysis and between two sessions. The EEG tracing was abnormal in 5 children. Two had paroxysmal aspecific slow waves towards the end of the sessions, with a fall in blood pressure, malaise and fainting. In 3 children EEG abnormalities - also present in the interdialytic period - were not clinically apparent. Long-term EEG monitoring in these cases distinguished between the electrical events that were related to dialysis and those that were not. It also suggested that, rather than being dialysis-dependent, these events frequently reflect a basic neurological disorder. PMID- 1868860 TI - Low doses of insulin as a treatment of tardive dyskinesia: conjuncture or conjecture? AB - Tardive dyskinesia (TD) induced by antipsychotic drugs represents a great concern for patients and psychiatrists. Considering its pathophysiological mechanisms, there exists a convergence towards the development of postsynaptic dopaminergic hypersensitivity as a possible cause of TD. Hypersensitivity following receptor blockade is the consequence of an increased number of receptors and such a synthesis is energy-dependent. In the brain, under normal conditions, energy is almost exclusively provided by glucose utilization. We thus hypothesized that, if glucose availability were reduced, the metabolically hyperactive structures should represent the best functional target of a reduction in fuel availability. Twenty chronic schizophrenic outpatients (13 males, 7 females), aged 20-67 (mean: 38.3), accepted to participate in this double-blind, placebo-controlled study. They were randomly assigned to either the insulin treatment group (10 patients) or to the insulin-placebo group (10 patients). They received a subcutaneous injection of 10 units of standard insulin or placebo at 10 a.m. From day 1 to day 15, injections were performed daily and, thereafter, every other week for 5 weeks totalizing 20 injections in 90 days. At day 7, the insulin treatment group showed a sharp decrease in the intensity of TD symptoms which persisted throughout the duration of the study. By contrast, no change in TD symptomatology was observed in the insulin-placebo-treated group. Although a direct effect on DA neurones, or at least the participation of such an effect, cannot be excluded, our data favor a role of decreased glucose availability in reversing receptor hypersensitivity. PMID- 1868861 TI - Mixed transcortical aphasia: clinical features and neuroanatomical correlates. A possible role of the right hemisphere. AB - This paper reports the clinical features of 2 patients affected by mixed transcortical aphasia. Both of them had extensive damage of the left hemisphere. Cerebral blood flow measurement showed a marked decrease in left-hemisphere flow. In particular, speech areas were found to be morphologically and functionally damaged. The present findings, together with a critical review of the literature, served as a starting point for a discussion of linguistic features, diagnostic criteria and classical neuroanatomical interpretation of mixed transcortical aphasia. The possible contribution of the right hemisphere in determining this aphasic syndrome is suggested. PMID- 1868862 TI - Partial complex epileptic seizures with ictal urogenital manifestation in a child. AB - Ictal sexual manifestations, like somatosensory genital phenomena, sexual emotions or sexual automatisms during a partial complex seizure, are very rare. So far the literature has above all described cases in adulthood. We report on a 6-year-old boy with partial complex epileptic seizures which led to confusion, oral and genital automatisms and the urge to urinate. During one epileptic seizure with these urogenital manifestations the EEG showed an epileptic rhythmic discharge over the left temporal region. PMID- 1868864 TI - Mapping of event-related potentials to auditory and visual odd-ball paradigms in controls. AB - The paper reports the results of recordings and maps of event-related potentials (ERPs) obtained in normal subjects. ERPs were recorded from 19 scalp electrode derivations using both visual and acoustic paradigms. In normal subjects, topographical distribution of all ERP components is described in detail. Our findings in normals suggest that the early modulation of stimulus-related potentials could be located in primary associative areas, and that N2, P3a, P3b, and SW have different distributions. PMID- 1868863 TI - Slow progressive bilateral posterior artery infarction presenting as agitated delirium, complicated with Anton's syndrome. AB - Three patients presented with an acute agitated delirium as the earliest sign of bilateral posterior cerebral artery infarction. All patients showed a unique slow progressive deterioration with a remarkably long interval between the first neuropsychological and subsequent visual and neurological symptoms, ranging from 3 to 30 days. Repeated CT scans demonstrated hypodensities in the posterior artery territory only after a long interval of 9-12 days, in case 3, and between 33 and 48 days in case 2. In the latter case MRI was still negative 33 days after onset. In 2 patients the cortical blindness was complicated with anosognosia for blindness. Clinical condition worsened progressively in all patients, leading to death, probably due to brainstem infarction. In all 3, the combination of clinical and radiological findings indicated a 'top of the basilar' distribution, which could be confirmed in two by autopsy. PMID- 1868865 TI - Neurocysticercosis: neurologic, pathogenic, diagnostic and therapeutic aspects. AB - Worldwide neurocysticercosis is the most common parasitic infection of the human brain and meninges. Clinical features of the illness vary with the stage of ova infection, but most problems arise when the mature cyst degenerates. Seizures, increased intracranial pressure, and focal neurologic signs then often develop. Computed tomography and magnetic resonance usually demonstrate Cysticercus cellulosae cysts in the brain. A new immunoblot test for antibodies to the cysticercus seems both sensitive and specific. Treatment with praziquantel or albendazole has hastened the disappearance of the cysts on computed tomography and improved clinical symptoms. PMID- 1868866 TI - Risks and benefits of therapy with flumazenil (Anexate) in mixed drug intoxications. AB - Flumazenil, the first specific benzodiazepine (BZD) antagonist, is one of the most innovative drugs to become available within the last few years. Flumazenil is indicated for the reversal of the centrally depressant effects of BZDs, in BZD induced anaesthesia, in BZD sedation in intensive care and in patients comatose after drug overdoses including BZDs. A conference of experts experienced in the treatment of mixed drug overdoses by various means, including flumazenil, was held in order to try to reach a consensus regarding the safe use of flumazenil in this indication. From the knowledge and experience gained to date, it was concluded that flumazenil may be useful and safe in the treatment of suspected BZD and mixed drug overdoses, provided that the appropriate precautions are observed. PMID- 1868867 TI - Stroke in a tertiary hospital in Saudi Arabia: a study of 372 cases. AB - Epidemiological studies have shown a consistent downward trend in the incidence and mortality of stroke in industrialized communities. There are however no reports on the pattern of stroke in Saudi nationals and expatriates in Saudi Arabia. The types and etiologies in 372 subjects (262 Saudis, 110 non-Saudis) are described. Males outnumbered females in the ratios of 2.2:1 and 8.2:1 for Saudis and non-Saudis, respectively. The frequency of stroke increased steadily with age until the 7th decade in Saudis but dropped sharply after the 6th in expatriates. The frequency of stroke types in Saudis was ischemic (61%), hemorrhagic (17%) and unspecified (22%) as against 46, 47, and 7% respectively in non-Saudis. Intracerebral hemorrhage was more frequent than subarachnoid hemorrhage (SAH) and was encountered more often in Saudis than in non-Saudis; SAH was 3 times more common in expatriates than in Saudis. The major predisposing factors for stroke were hypertension, diabetes mellitus, and cardiac disorders. Abnormal hemoglobinopathies, especially sickle cell anemia, were rare. The differences observed in the age and sex distribution and in the stroke pattern between Saudi nationals and expatriates most likely reflect the demographic structure existing in Saudi Arabia. PMID- 1868868 TI - Monochorea caused by a striatal lesion. AB - A 76-year-old man developed choreic movement restricted to the arm. Computed tomography suggested an old infarction mainly involving the head of the right caudate nucleus. Monochorea may indicate a striatal lesion and suggests the somatotopic localization. PMID- 1868869 TI - Mapping of event-related potentials to auditory and visual odd-ball paradigms in patients affected by different forms of dementia. AB - The paper reports the results of recordings and maps of event-related potentials (ERPs) in patients with Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and in subjects affected by dementia in multiple sclerosis (MS). ERPs were recorded from 19 scalp electrode derivations using both visual and acoustic paradigms. In 43% of AD patients, ERPs were normal; in 20%, although present, ERP components were delayed, while in the other 37% none of the N2 and P3 peaks could be recorded, because of abnormal topography of potentials on the scalp. In patients with PSP, the normal ERP sequence was not identified. In patients with MS delayed ERPs (50%), abnormal topography of ERPs (30%) and absence of ERPs (20%) were observed. The follow-up of AD patients showed a progressive alteration of ERPs. ERP topography alterations were observed in AD, PSP and MS patients with poorest cognitive performances. PMID- 1868870 TI - Recurrent Fisher's syndrome with immunological abnormalities and replicated laterality. AB - A case of Fisher's syndrome which recurred 10 years apart was reported. Laterality of cranial nerve findings in the initial episode was replicated in the recurrence. Some kind of localized immune sensitization is supposed to play a role in replicating such a laterality. Increased CD4/CD8 ratio and elevated IgE were noted, which suggests immunological behavior in Fisher's syndrome similar to that in Guillain-Barre syndrome. PMID- 1868871 TI - A monoclonal antibody blocking the Schistosoma mansoni 28-kDa glutathione S transferase activity reduces female worm fecundity and egg viability. AB - The protective effects of two different monoclonal antibodies (mAb) raised against the Schistosoma mansoni 28-kDa glutathione S-transferase (Sm 28 GST) were investigated. Two mAb of the same isotype (IgM) have been selected according to the blocking effect on Sm 28 GST enzymatic activity (S13) or the lack of blockade (H12). When passively transferred into Fischer rats, both S13 and H12 significantly reduced the worm burden. In BALB/c mice clear effects on female worm fecundity and egg viability were observed when the S13 mAb was transferred; these effects included significantly reduced loads of intestinal eggs, reduced egg hatching rates and an increased proportion of non-living eggs. No effect on egg production and egg hatching was observed in H12-treated mice. In addition, worm pairs recovered from S13-but not H12-treated mice laid significantly fewer eggs in vitro, and normal worm pairs incubated in vitro with the S13 mAb produced significantly fewer eggs than those incubated with H12 mAb. The impairment of egg hatching ability was also reproduced in vitro by the S13 mAb. These data suggest the existence of two different effector mechanisms induced by immunization with Sm 28 GST. The effect on the schistosome worm burden appears to be independent of GST activity whereas the effect on S. mansoni female fecundity and egg viability seems to be significantly linked to the inactivation of the enzymatic site. PMID- 1868872 TI - Preferential development of pre-B lymphomas with drastically down-regulated N-myc in the E mu-ret transgenic mice. AB - We established one transgenic mouse line which developed pre-B leukemic lymphomas by introducing ret cDNA driven by the SV40 promoter and the mouse immunoglobulin (Ig) enhancer. Lymphomas developed not only in the lymph nodes and the spleen but also in the thymus between the ages of 7 and 21 weeks. Analyses of cell surface phenotypes and Ig gene rearrangement revealed that these tumors were surface IgM B220+ pre-B lymphomas. The rearrangement pattern of the Ig heavy chain locus indicated that the tumor cells were mono- or oligoclonal. Northern blot analysis showed that the ret transgene was expressed at a high level not only in the tumors but also in the prelymphomatous lymphoid tissues. We found that the expression of N-myc was dramatically down-regulated in the tumor cells, while the expression of c-myc was rather stable. Further experiments demonstrated that ret gene product did not directly down-regulate the expression of N-myc in transformed pre-B cell lines by in vitro transfection assay. From these results, we conclude that under the control of Ig enhancer, the ret transgene affected B lymphocytes at the early maturation stage as a prerequisite for transformation, preferentially generating a unique maturation stage of pre-B lymphomas whose N myc expression was developmentally down-regulated. PMID- 1868873 TI - Isolation of normal human follicular dendritic cells and CD4-independent in vitro infection by human immunodeficiency virus (HIV-1). AB - Immunohistological and electron microscopy studies of lymph nodes from patients infected with the human immunodeficiency virus 1 (HIV-1) demonstrated that follicular dendritic cells (FDC), the antigen-presenting cells of the B cell system, contain and may produce the virus. To elucidate the mode of infection of FDC with HIV-1 in vitro we developed an improved method for the preparation of single-cell suspensions of viable FDC with high purity (greater than 90% FDC). These isolated FDC were subjected to human T cell leukemia virus IIIB infection, which was monitored after 4 days in culture using the polymerase chain reaction. We were able to demonstrate that normal human FDC are highly susceptible to infection by HIV-1. Inhibition experiments with the monoclonal antibody OKT4a demonstrate that this infection is independent of the CD4 molecule. PMID- 1868874 TI - Isolation and molecular characterization of the B cells producing the paraprotein in a case of benign monoclonal gammapathy in C57BL mice. AB - Benign monoclonal gammapathy (BMG) is defined as a benign monoclonal B cell proliferative disorder characterized by the presence of a persisting component of homogenous immunoglobulins (H-Ig) in the serum. A possible role of antigenic stimulation in the development of BMG has been suggested. From a C57BL mouse, a murine model for BMG, we have isolated clonally related B cells in order to investigate the occurrence of somatic mutations in the variable heavy chain (VH) region of the genes of H-Ig-producing B cell clones. Therefore, B cells were immortalized by hybridoma technology. The hybridomas were screened for resemblance of the serum H-Ig component by Wieme agar electrophoresis, followed by immunoblotting and isoelectrofocusing. Clonal relationship was investigated by Southern blot analysis using a JH probe. In this way we isolated five hybridomas producing an IgG2a, kappa that was identical to the original serum H-Ig component according to testing with anti-idiotypic antisera. mRNA sequencing of four hybridomas showed only one base pair difference in the VH genes. This particular gene belonged to the J558 VH gene family. When compared to the most closely related known VH sequence, three base pair differences were found. The almost complete absence of base pair differences in the VH genes of the four sequenced hybridomas, compared with an independently derived hybridoma, suggests that the same germ-line VH gene has been used and that somatic mutations were infrequent in our BMG clone. PMID- 1868875 TI - Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis. AB - B cells undergo selection within germinal centers on the basis of their capacity to be activated by antigen held on follicular dendritic cells. Isolated germinal center B cells in culture kill themselves by apoptosis but this is prevented if their receptors for antigen are cross-linked. In this study it is confirmed that almost all germinal center B cells, unlike other B cells, do not express the 25 kDa protein encoded by the bcl-2 oncogene. Cross-linking the surface Ig of isolated germinal center cells causes them to express bcl-2 protein. Two other stimuli which inhibit the entry of germinal center cells to apoptosis result in the expression of bcl-2 protein. These stimuli are: (a) CD40 antibody and (b) recombinant 25-kDa fragment of the CD23 protein plus recombinant interleukin 1 alpha. Respectively, these induce germinal center cells to differentiate to resting B cells or plasmablasts. Dual-fluorescence studies on small lymphocytes confirm the presence of bcl-2 protein in mitochondria but show that this is also present in other extra-nuclear areas. Burkitt lymphoma cells have a phenotype which indicates that they are neoplastic cells of germinal center origin. The expression of bcl-2 protein by Burkitt lymphoma lines was also studied. Burkitt lines which retain the phenotype of fresh Burkitt lymphoma cells can be induced to enter apoptosis on culture with the Ca2+ ionophore ionomycin. These cells were found not to express bcl-2 protein. By contrast, Burkitt lines which have drifted towards a lymphoblastoid cell line phenotype and are resistant to the induction of apoptosis express high levels of the bcl-2 protein. The findings support the concept that the susceptibility of germinal center cells to entering apoptosis is associated with their lack of expression of bcl-2 protein. Aberrant expression of bcl-2 protein by some neoplastic germinal center cells may allow survival in situations where their normal counterparts die. PMID- 1868876 TI - Regulation of interleukin 2 production, interleukin 2 mRNA expression and intracellular glutathione levels in ex vivo derived T lymphocytes by lactate. AB - The concentration of L-lactate in the blood plasma of higher vertebrates is about 1 mM but can be as high as 30 mM under certain physiological and pathological conditions or in the vicinity of glycolytically active cells including macrophages. Here we report that high but physiologically relevant concentrations of lactate increase the expression of interleukin 2 (IL 2)-specific mRNA and the production of IL 2 activity in cultures of mitogenically stimulated T cells. Lactate supports IL 2 production most effectively if added 0-8 h after T cell stimulation and only in cultures of CD4+ but not of CD8+ T cells. In contrast to the DNA synthesis activity in these cell cultures, IL 2 production is not augmented but rather inhibited by exogenous glutathione (GSH). Lactate causes a reduction of intracellular GSH levels, and lactate-containing cultures require accordingly higher extracellular cysteine concentrations than control cultures to achieve similar intracellular GSH levels. In view of the strong variations of extracellular lactate concentrations in vivo, our experiments suggest that lactate may be part of a previously unknown mechanism by which the metabolic microenvironment modulates gene expression in T cells. PMID- 1868877 TI - Apoptosis is associated with the extensive B cell death in the sheep ileal Peyer's patch and the chicken bursa of Fabricius: a possible role in B cell selection. AB - The ileal Peyer's patch (PP) and the bursa of Fabricius have major roles in populating the B cell system in sheep and chickens, respectively. These tissues contain greater than 90% B cells and possess a massive proliferation index with greater than 5% of B cells entering mitosis per hour. Paradoxically, almost all of the B cells produced in these sites rapidly die in situ. Here we show that the extensive B cell death occurring in the ileal PP and bursa is associated with apoptosis. Gel electrophoresis of ileal PP cell DNA from 7-14 week-old lambs and bursal cell DNA from 4-week-old chickens demonstrated a laddering of DNA in multiples of approximately 200 bp, a pattern indicative of apoptosis. In sheep, the intensity of the laddering pattern seen after agarose gel electrophoresis was always greater with ileal PP cell DNA compared with thymocyte DNA, and usually greater than jejunal PP cell DNA. Likewise, DNA isolated from chicken bursal cells and mouse PP cells always exhibited a more intense laddering pattern than chicken or mouse thymocytes, respectively. When placed in culture ileal PP cells died rapidly less than 40% viable cells were recovered after 24 h. Within 6 h of culture many ileal PP cells exhibited an apoptotic appearance in that they contained condensed chromatin and fragmented nuclei. Moreover, greater than 55% of total cellular DNA was fragmented. Compared with thymocytes, ileal PP cells underwent DNA fragmentation to a much greater extent and with a faster time course in short-term culture. We propose that cell death by apoptosis may make an important contribution to B cell development in the lamb ileal PP and the chicken bursa. Apoptosis may provide a mechanism for the diversification of the B cell immune repertoire and/or the selection of non-self reactive B cells. PMID- 1868878 TI - Effects of trimebutine on cytosolic Ca2+ and force transitions in intestinal smooth muscle. AB - The effects of trimebutine maleate on cytosolic free Ca2+ and force transitions in the guinea-pig taenia cecum were studied by fura-2 fluorometry and tension recording. The addition of 80 mM K+ induced a transient increase in cytosolic free Ca2+ concentration ([Ca2+]i) and tension, followed by a sustained increase. Trimebutine (10 microM) suppressed both [Ca2+]i elevation and tension development. The tonic responses were more potently inhibited than the phasic responses. Phasic components gradually increased as the added K+ increased (10-40 mM). The relationship between the peak increases in [Ca2+]i and tension was not affected by trimebutine (10 microM). This means that trimebutine does not affect the Ca2+ sensitivity of contractile elements. In a high K+ and Ca(2+)-free medium, carbachol (10 microM) or caffeine (30 mM) caused transient [Ca2+]i elevation and tension development in the smooth muscle. Trimebutine (10 microM) decreased the amplitude of both responses. Trimebutine (10 microM) inhibited the spontaneous fluctuations in [Ca2+]i and motility of taenia cecum in the presence of tetrodotoxin (TTX; 0.3 microM). These results suggest that trimebutine has two types of inhibitory actions on intestinal smooth muscle; one, the inhibition of Ca2+ influx through voltage-dependent calcium channels, and the other, the inhibition of Ca2+ release from intracellular storage sites. PMID- 1868879 TI - Neuropharmacology of the muscarinic antagonist telenzepine in myenteric ganglia of the guinea-pig small intestine. AB - Intracellular recording methods were used to investigate the actions of the putative M1 muscarinic receptor antagonist telenzepine on the electrical and synaptic behavior of myenteric neurons. Telenzepine had no effect on resting membrane potential, input resistance, excitability and antidromic potentials in both AH/type 2 and S/type 1 neurons, when applied in concentrations of 0.1-2000 nM, although higher concentrations (10-100 microM) did have a significant non specific effect on the postsynaptic membrane. Micromolar concentrations of telenpzepine (1-2 microM) had no effect on excitatory responses to substance P, vasoactive intestinal peptide, the nicotinic agonist 1,1-dimethyl-4 phenylpiperazinium or the nicotinic action of acetylcholine. Nicotinic fast excitatory postsynaptic potentials were also unaffected by 2 microM telenzepine. In contrast, at submicromolar concentrations (100 nM), telenzepine abolished responses to either muscarine or the muscarinic component of the acetylcholine response. The excitatory effect of muscarine at postsynaptic M1 receptors was dose dependently inhibited by telenzepine (0.1-1000 nM) at concentrations which had no effect on the electrical properties of the cells. This effect was slowly reversible, usually requiring more than 60 min for significant recovery. The threshold dose of telenzepine as an antagonist of the muscarinic depolarization in AH/type 2 neurons was in the range of 0.1-1 nM. The IC50 concentration of telenzepine needed to abolish the response was 8.5 nM. A small proportion of stimulus-evoked slow excitatory postsynaptic potentials in both AH/type 2 and S/type 1 cells were abolished by 1 microM telenzepine, while the majority of them remained unaffected, indicating that some slow excitatory postsynaptic potentials are mediated by the muscarinic action of released acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868880 TI - Effects and aftereffects of ibogaine on morphine self-administration in rats. AB - Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addition to opiate and stimulant drugs. As a preclinical test of this claim, the present study sought to determine if ibogaine would reduce the intravenous self-administration of morphine in rats. Ibogaine dose dependently (2.5-80 mg/kg) decreased morphine intake in the hour after ibogaine treatment (acute effect) and, to a lesser extent, a day later (aftereffect); while the acute effect could be attributed to abnormal motor behavior (whole body tremors), the aftereffect occurred at a time when ibogaine should have been entirely eliminated from the body and when there was no obvious indication of ibogaine exposure. In some rats, there was a persistent decrease in morphine intake for several days or weeks after a single injection of ibogaine; other rats began to show such persistent changes only after two or three weekly injections whereas a few rats were apparently resistant to prolonged aftereffects. Aftereffects could not be attributed to a conditioned aversion. Although ibogaine also depressed responding acutely in rats trained to bar-press for water, there was no evidence of any aftereffect a day or more later; the interaction between ibogaine and morphine reinforcement was therefore somewhat specific. Further studies are needed to characterize the nature of the ibogaine-morphine interaction as well as to determine if ibogaine also affects the self-administration of other drugs. PMID- 1868881 TI - Nocloprost, a unique prostaglandin E2 analog with local gastroprotective and ulcer-healing activity. AB - Nocloprost (9 beta-chloro-16,16-dimethyl prostaglandin E2 (PGE2)) was examined for gastroprotective and ulcer-healing activity and compared to 16,16-dimethyl PGE2 (dmPGE) in rats. Nocloprost given intragastrically (i.g.) at various doses (0.01-10 micrograms/kg) 30 min before 100% ethanol, acidified aspirin (ASA), acidified taurocholate, water immersion, or restraint stress dose dependently prevented the formation of gastric lesions, the ID50 values being 0.25, 0.58, 0.06 and 0.12 micrograms/kg, respectively. The gastroprotection provided by nocloprost given i.g. was somewhat enhanced by the presence of acid in the stomach and was reduced by inhibition of gastric acid secretion. Nocloprost given s.c. also showed protective activity against ethanol damage but was ineffective when applied intraduodenally. The protective effect of nocloprost lasted about 8 h whereas that induced by dmPGE lasted 6 h. Nocloprost (0.01-100 micrograms/kg) given i.g. failed to affect gastric acid secretion or intestinal secretion (enteropooling) but prevented the increased gastroduodenal alkaline secretion. Nocloprost alone caused only a transient increase in the mucosal blood flow but prevented the fall in blood flow caused by 100% ethanol. [3H]Nocloprost was absorbed from the small intestine but was then taken up and metabolized by the liver and excreted into the bile so that very little reached the systemic circulation in an unchanged form. Nocloprost, unlike dmPGE, accelerated the healing of chronic gastric ulcerations and enhanced mucosal growth. We conclude that nocloprost is a locally active PGE2 analog with high cytoprotective and ulcer-healing efficacy. PMID- 1868882 TI - Differential effects of neuropeptide Y and opioids on neurogenic responses of the perfused rat mesentery. AB - In perfused rat mesentery transmural nerve stimulation activates both adrenergic and capsaicin-sensitive sensory nerves. When adrenergic nerves were blocked with guanethidine and smooth muscle tone was increased, transmural nerve stimulation caused a dilator response which was attenuated by tetrodotoxin and abolished by capsaicin. Indomethacin increased the vasodilator response to transmural nerve stimulation, but did not affect the dilation to calcitonin gene-related peptide. Neuropeptide Y (NPY) potentiated vasoconstrictor responses to transmural nerve stimulation, but suppressed capsaicin-sensitive vasodilation, an effect which was unaltered by indomethacin. Opioid agonists selective for mu, delta or kappa receptors, DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin), DPDPE ([D-Pen2,D Pen5]enkephalin) and ethylketocyclazocine, had no effect on the vasoconstrictor response to transmural nerve stimulation. DAMGO and DPDPE significantly inhibited vasodilator responses to transmural nerve stimulation, but ethylketocyclazocine was without effect. After treatment with indomethacin, DAMGO still inhibited the vasodilator response, but DPDPE was no longer effective. Prejunctional control of transmitter release by NPY or opioids is dependent on the specific nerve type as well as, in some cases, the participation of endogenous prostaglandins. PMID- 1868884 TI - Analysis of carbohydrates in human lens epithelium by high performance liquid chromatography of nitrobenzoate derivatives. PMID- 1868883 TI - Effects of cyproheptadine and pizotifen on central muscarinic receptors. AB - The affinities of cyproheptadine, pizotifen and (+/-)-quinuclidinyl xanthane-9 carboxylate hemioxylate (QNX) were determined at muscarinic autoreceptors and postsynaptic (IP1 formation) receptors in rat hippocampal slices. The affinity values for QNX were 8.2 and 8.5 respectively. Cyproheptadine and pizotifen were less potent than QNX. Pizotifen was slightly (2-fold) less active at antagonizing IP1 formation than blocking the autoreceptors whereas cyproheptadine was equally active at antagonizing the two hippocampal muscarinic receptors. PMID- 1868885 TI - Characterization of the major matrix degrading metalloproteinase of human corneal stroma. Evidence for an enzyme/inhibitor complex. AB - The human cornea is an avascular, highly organized tissue with the unique property of transparency. While the extracellular matrices of this tissue are composed of a variety of collagen types, proteoglycans and glycoproteins, little is known of the normal degradation and remodeling of these components. We examined the capacity of organ cultured human ocular tissues to produce and secrete metalloproteinases, a family of related enzymes capable of digesting a variety of extracellular matrices. We demonstrated that while enzymatic activities similar to type I collagenase and stromelysin are produced, the predominant activities of the corneal stroma and keratocyte cultures are a 68-kDa gelatinase. In our hands, this enzyme does not appear to be induced significantly by phorbol esters in vitro. In addition, this enzyme appears to be secreted as a complex with a 21-kDa protein that functions as an enzymatic inhibitor. Moreover, the keratocytes also produce a 28-kDa inhibitor which has similar properties to tissue inhibitor of metalloproteinase (TIMP). PMID- 1868886 TI - Requirement of insulin or IGF-1 for the maintenance of retinyl ester synthetase activity by cultured retinal pigment epithelial cells. AB - Previous work from these laboratories showed that the retention of retinyl ester synthetase activity by cultured human retinal pigment epithelium is up to tenfold greater with PM medium (Medium 199 plus insulin, other added defined components, 1% serum and 1% retina extract) than with conventional culture media. The present work shows that insulin is the component of PM medium required for maintenance of ester synthetase activity and that insulin-like growth factor type 1 (IGF-1) also is effective at maintaining ester synthesis. In addition, insulin can maintain ester synthetase activity in cultured rat RPE. Preliminary dose-response measurements provide additional support for these findings and strongly suggest that both insulin and IGF-1 are maximally effective at physiological concentrations (1-10 ng ml-1). PMID- 1868887 TI - Proteoglycans in the mouse interphotoreceptor matrix. IV. Retinal synthesis of chondroitin sulfate proteoglycan. AB - To determine whether the mouse retina contributes chondroitin sulfate proteoglycan (CS-PG) to the interphotoreceptor matrix (IPM), 35SO4(2-) was used as a tracer for newly synthesized proteoglycan by retinas maintained in vitro in the absence of pigment epithelium. Following incubation with the tracer for 3 hr, the 35S-labeled proteoglycans present in the incubation medium and associated with isolated photoreceptor outer segments were analyzed separately. Proteoglycan was extracted with 4 M guanidine, and then separated on a G-25 column followed by DEAE ion exchange chromatography in the presence of 8 M urea. The proteoglycan fraction was eluted with a linear NaCl gradient of 0.15-1.0 M. Eluted 35S-labeled macromolecules were susceptible to chondroitinase AC and ABC degradation, indicating that virtually all the 35S-labeled proteoglycan synthesized by the mouse retina and secreted into the incubation media is of the chondroitin sulfate type. In parallel autoradiographic analysis of retinas following 35SO4(2-) incubation, silver grains were present over all retinal compartments, with 41-48% associated with the photoreceptor layer. Quantitative autoradiography of retinas following chondroitinase AC digestion of fixed retinas revealed significant (P less than 0.025) reduction in silver grains associated with the photoreceptor outer segment layer as compared to controls. These combined biochemical and autoradiographic studies indicate that the retina, possibly the photoreceptors, synthesize at least a portion of the CS-PG present in the IPM of the mouse. PMID- 1868888 TI - Mannose-sensitive HRP endocytosis by the retinal pigment epithelium. AB - Mannose-sensitive endocytosis by rat retinal pigment epithelium (RPE) explants was characterized using the mannose-rich glycoprotein horseradish peroxidase (HRP). The number of HRP-containing endosomes in the RPE was morphologically quantitated by light microscopy while the amount of HRP ingested was biochemically quantitated by enzyme assay. HRP internalized via a mannose sensitive receptor was differentiated from fluid-phase uptake in competitive inhibition studies using D-mannose. Morphological results showed that most HRP containing endosomes formed within the first 15 min of incubation and showed little increase in number during 4 hr of continued incubation with HRP. In contrast, the biochemical assay showed a steady increase in the amount of HRP in RPE endosomes measured over time. The addition of 10 mM D-mannose to the incubation medium was associated with a significant decrease in both the number of HRP-containing endosomes and the amount of HRP ingested by RPE explants. Values indicate that half of the total uptake of HRP is mediated by a mannose sensitive receptor while the balance is ingested via non-specific fluid-phase endocytosis. PMID- 1868890 TI - The blueness of stem cells. PMID- 1868889 TI - Diamide induces reversible changes in morphology, cytoskeleton and cell-cell coupling in lens epithelial cells. AB - The isolated frog lens epithelium can be maintained with its cell shape, cytoskeletal organization and membrane electrophysiological characteristics intact for more than 24 hr. Perifusion with the permeant oxidant diamide (1 mM) led to drastic, but reversible, changes in all the above parameters. After a 20 min exposure to diamide, the regular polygonal arrangement of the epithelial cells become increasingly disrupted as the cells reorganized and a 'rosette' pattern formed. The cells at the edges of the rosette pulled apart from one another while those in the centre maintained a relatively normal appearance. Blebs formed on the apical surface of all of the cells on prolonged exposure and the internal structure was also found to be severely disrupted. The cytoplasm became granular, vacuolated and the nucleus had a banded, non-homogeneous appearance. Phalloidin staining of F-actin microfilaments revealed that there was a general disruption of organization, with actin losing its association with the membrane. The microtubule array, organized around the centrosome, was also severely disrupted although microtubules were still discernible in most cells. During exposure to diamide the membrane potential depolarized and both electrical and dye coupling, which are normally extremely efficient in these cells, were disturbed. If the epithelium was exposed to 1 mM diamide for more than 45 min then all of the above changes were irreversible and cell death followed. If exposure was restricted to less than 30 min, then all of the above changes occurred and, in fact, progressed for over 1 hr; but if the epithelium was perifused for a further 20 hr in control medium, then most of the changes were reversible. PMID- 1868891 TI - In vitro studies on the radiosensitivity of multipotent hemopoietic progenitors in canine bone marrow. AB - The in vitro radiation response to 280-kV x-rays (does rate 72 cGy/min) of multipotent hemopoietic progenitor cells, mixed colony-forming units (CFU-mix), from canine bone marrow was assayed and compared to the radiation response characteristics of early erythroid progenitors, erythroid burst-forming units (BFU-E). To improve the colony-forming efficiency, the effect of various bone marrow cell separation techniques on colony formation of both progenitors was examined. The separation of bone marrow aspirates by discontinuous buoyant gradient centrifugation using the lymphocyte separation medium Lymphoprep with a density of 1.070 g/ml allowed the establishment of reproducible survival curves. The survival curves for both progenitors were strictly exponential, and CFU-mix were found to be more radiosensitive (D0 = 12 +/- 2 cGy) than BFU-E (D0 = 16 +/- 2 cGy). PMID- 1868892 TI - Platelet factor 4 mRNA expression in human erythroleukemic cells: regulation by phorbol esters and certain cytokines. AB - Developing megakaryocytes are distinguished from progenitor cells by the appearance of platelet proteins such as platelet factor 4 (PF 4). The human erythroleukemic cell line HEL can also be induced to produce PF 4 by incubation in phorbol esters. HEL cells were used here as a model system in which to study the phenomenon of inducible PF 4 production at both the mRNA and protein levels. The cytokines interleukin 1 beta (IL-1 beta), interleukin 3 (IL-3), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (EPO), and transforming growth factor-beta (TGF-beta) were also evaluated for their effects on PF 4 mRNA induction in HEL cells. PMID- 1868893 TI - Plasma membrane properties regulating the sensitivity of leukemia, lymphoma, and solid tumor cells to merocyanine 540-sensitized photoirradiation. AB - Merocyanine 540 (MC 540) is a photosensitizing dye that has been used in a phase I clinical trial for the purging of leukemia and lymphoma cells from autologous bone marrow grafts. In this paper we examine the role of plasma membrane negative charge, plasma membrane fluidity, and plasma membrane hydrophobicity in the regulation of a cell's susceptibility to MC 540-sensitized photoirradiation. Among solid tumor cells, we found an inverse correlation between surface electronegativity, affinity for dye molecules, and susceptibility to MC 540 sensitized photoinactivation. That is, the least electronegative cells bound the highest amount of dye and were the most susceptible to dye-sensitized photoirradiation. By contrast, no such correlations were found among leukemia/lymphoma cells. This suggested that dye binding and susceptibility to MC 540-mediated photodynamic damages are regulated differently in hematopoietic/lymphopoietic and solid tumor cells. PMID- 1868894 TI - Erythroid progenitors in tumor-bearing mice: erythroid inhibitory factors produced by adenocarcinoma-755. AB - Adenocarcinoma-755-bearing C57BL/6 mice developed anemia with the growth of the tumors. The numbers of granuloid and monocytoid progenitors (colony-forming unit in culture, CFU-C) of the bone marrow and spleen and the peripheral blood WBC counts increased in tumor-bearing mice. The erythroid progenitors (erythroid colony-forming units, CFU-E; erythroid burst-forming units, BFU-E) of the bone marrow showed a marked decrease, overcoming their increase in the spleen in tumor bearing mice. Fractionation of conditioned medium of tumor cells led to the isolation of a protein of 80-kd molecular weight that stimulated murine CFU-C growth and inhibited the CFU-E and BFU-E growth in a dose-dependent manner. These results indicate that erythroid inhibitory factors produced by tumors exist in tumor-bearing mice. Erythroid inhibitory factors might also exist in non hematological malignancies of humans, and they might be one of the mechanisms of anemia. PMID- 1868895 TI - Recombinant human granulocyte-macrophage colony-stimulating factor promotes megakaryocyte maturation in nonhuman primates. AB - Megakaryocytes are responsive to several nonlineage-specific cytokines in vitro. In this study, we examined the in vivo effects of recombinant human granulocyte macrophage colony-stimulating factor (rh GM-CSF) on late stages of megakaryocytopoiesis in the rhesus monkey. Four rhesus monkeys were given 10 micrograms/kg body weight/day of rh GM-CSF s.c. in two divided doses daily for 8 days. Megakaryocyte maturation was evaluated serially by measuring nuclear ploidy and cytoplasmic size. GM-CSF-treated monkeys developed significant shifts in ploidy distribution from days 3 through 15 (p less than or equal to 0.001), with increased frequencies of 64N and 128N megakaryocytes. Mean megakaryocyte size increased 92.5% on day 9, paralleling the increase in DNA content, although megakaryocyte size within ploidy groups did not increase. Megakaryocyte number remained unchanged following rh GM-CSF treatment. The platelet count responses were variable, and mean platelet volume did not change. The present study demonstrates that therapeutic doses of rh GM-CSF stimulate megakaryocyte endomitosis and increase mean size. The data indicate that GM-CSF is effective in promoting the maturation stage of megakaryocyte development but does not result in a consistent thrombopoietic response. PMID- 1868896 TI - Quantitation of human erythroid-specific porphobilinogen deaminase mRNA by the polymerase chain reaction. AB - Porphobilinogen deaminase (PBG-D), the third enzyme in the heme synthetic pathway, possesses two isoforms encoded by distinct mRNAs that are the result of transcription of a single gene from two promoters through differential splicing. During erythroid differentiation, only the expression of the erythroid-specific isoform (E-PBGD) was increased. A system was developed to evaluate genetic expression of E-PBGD in samples limited in cell number and/or mRNA copy. Total RNA from human cells was reverse-transcribed and amplified by the polymerase chain reaction in the same tube with an internal standard that is an in vitro transcript of a cDNA differing from its sample counterpart by a few restriction sites and 24 bp (10%) in the target region. The primers spanned through regions where sample and standard templates were identical in sequence. Amplified templates were resolved by restriction enzyme digestion and gel electrophoresis and quantified by densitometer tracing of corresponding bands on autoradiograms. When an appropriate amount of internal standard is present in the reaction mixture, the ratio of amplified sample versus standard template is proportional to the amount of sample RNA and it is therefore possible to calculate the number of specific mRNA molecules in the original sample. PMID- 1868897 TI - Response of CFU-GM to increasing doses of rhGM-CSF in patients with aplastic anemia. AB - The aim of this study was to test whether large amounts of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) are capable of promoting the growth of hemopoietic progenitors from patients with marrow failure. For this purpose 0.1, 100, 1000, 10,000 and 20,000 ng/ml of rhGM-CSF were added to 10(5) light-density (adherent cell-depleted) bone marrow cells from 9 normal controls and from 52 patients with aplastic anemia, 25 cases of which were transfusion-dependent (Tx-D) aplastic anemia (AA) and 27 of which were transfusion-independent (Tx-I) aplastic anemia (AA). A dose-dependent increase of granulocyte-macrophage colony-forming units (CFU-GM) was observed in healthy donors, from 81 to 247 colonies at 0.1 and 1000 ng/ml of rhGM-CSF, with a plateau thereafter. Tx-I AA patients showed the best increase of CFU-GM in response to colony-stimulating factor, from 0.1 to 32.7 mean colonies at 0.1 and 20,000 ng/ml of rhGM-CSF, and the increment was greater when compared to controls. The ratio of CFU-GM grown from these patients and controls was 1:810 at 0.1 ng/ml of rhGM CSF and 1:7.9 at 20,000 ng/ml. Eleven patients were studied at diagnosis; there was no in vitro response to rhGM-CSF (0 and 1.8 mean colonies/10(5) cells at 0.1 and 10,000 ng/ml). Overall, Tx-D AA patients showed minimal increments of CFU-GM growth at very high doses of rhGM-CSF. Two suggestions come from this study: 1) maturation of CFU-GM from recovering AA patients appears to require larger doses of GM-CSF than normal controls, and 2) very high doses of rhGM-CSF have little or no effect on CFU-GM growth in AA patients. This may be relevant for clinical studies designed to improve hemopoiesis in patients with marrow failure. PMID- 1868898 TI - Hemotoxic effects on mice of combined administration of azidothymidine and acyclovir. AB - This study reports the effects of a combination of azidothymidine (AZT) plus acyclovir (ACV) on both pluripotent (spleen colony-forming units, CFU-S) and committed (granulocyte-macrophage colony-forming units, CFU-GM; erythroid burst forming units, BFU-E) murine hemopoietic progenitors. Administration of AZT alone was associated with severe hemotoxicity, as shown by the marked decrease of all the hemopoietic progenitor populations tested, that is, CFU-S, CFU-GM, and BFU-E. This, however, was followed by a prompt recovery of hemopoiesis. Administration of ACV alone did not modify the hematological parameters studied, whereas the combined administration of AZT and ACV led to changes in peripheral blood cells and bone marrow hemopoietic progenitors that were, on the whole, not significantly different from those observed with AZT alone. Only the decrease in CFU-S was significantly more severe, but their recovery was as rapid as that of the committed progenitors. Thus, in this experimental setting, the addition of ACV to AZT does not appear to increase the hemotoxicity of the latter. PMID- 1868899 TI - Erythropoietin: evolving clinical applications. PMID- 1868900 TI - What we can say from in vitro culture work: limitation of interpretation. PMID- 1868902 TI - Effect of video feedback on the performance of a weight shifting controlled tracking task in subjects with parkinsonism and neurologically intact individuals. AB - This study compared the performance of a visual motor task, accomplished by standing weight shifting, of 34 people with Parkinson's disease (P.D.) and 34 neurologically intact (N.I.) subjects. Twenty of the P.D. subjects were in Stage 1 and 14 were in Stage 2. The performance of ten, 10-s trials was each examined under two feedback (FB) conditions: continuous video display of performance and end of trial position. Visual FB was composed of displaying a target and cursor on a video monitor, with the cursor controlled by the subject through weight shifting on a platform interfaced with a microprocessor. Once the cursor was centered, the computer then transferred the target to the upper right quadrant of the monitor, and the subject was required, through weight shifting, to relocate the cursor inside the target. ANOVA with repeated measures was used for data analysis. The visual motor performance of P.D. subjects was significantly worse than that of N.I. (P less than 0.01), as well as between FB conditions (P less than 0.01). The interaction of the FB condition by trial segment was significant (P less than 0.01), as was the interaction of group membership by the trial segment (P less than 0.01). FB condition and group membership did not significantly interact, confirming that performance was worse under end of trial position FB, regardless of group membership (P less than 0.01). Post hoc analysis yielded significant differences (P less than 0.05) in task performance between N.I. and P.D. subjects after the first second of the trials regardless of FB condition. In either group, significant differences between continuous visual FB and end of trial position FB (P less than 0.05) were verified after the fourth second. Performance between N.I., Stage 1, and Stage 2 P.D. subjects revealed significant differences (P less than 0.01) among all three groups, regardless of FB condition. One of the revealing aspects of this investigation was the establishment of significant differences in visual motor performance of individuals in the early stages of the disease compared to previous reports of extremity deficits in the later stages. PMID- 1868901 TI - Beta-nerve growth factor (beta-NGF) mRNA expression in the parkinsonian adrenal gland. AB - The adrenal gland is a well-demonstrated source for different neurotrophic factors. The presence of the beta-nerve growth factor (beta-NGF) mRNA in the adrenal tissue used for grafting in a Parkinsonian patient is reported here. Adrenal samples were obtained on the day of implantation, and a specific cDNA was synthesized after the extraction of total RNA using a synthetic oligonucleotide as a reverse transcription primer. A 168-bp portion of the cDNA was amplified using two other oligonucleotides as Taq polymerase primers in a polymerase chain reaction. Thirty-two cycles of amplification were performed. The amplification products were identified by agarose gel electrophoresis and Southern blot analysis as a single DNA band hybridizing with a third beta-NGF specific oligonucleotide. The identity of the fragment was confirmed by DNA sequencing. Quantitative analysis demonstrated a beta-NGF mRNA concentration exceeding 5 fg/micrograms of total adrenal RNA. These findings add NGF to the other neurotrophic factors produced by the gland (i.e., basic fibroblast growth factor) and demonstrate the retained functional capacity of the Parkinsonian adrenal to express the beta-NGF mRNA. All these data may assume relevant meaning for neurotransplantation research. PMID- 1868903 TI - Vergence control of central and peripheral disparities. AB - The results of previous studies using either small or large target configurations suggest that open-loop (OL) vergence response dynamics may depend on the peripheral extent of the target. To investigate systemically the effect of peripheral target extent on dynamic vergence control, OL vergence responses to central, peripheral, and central-plus-peripheral targets were recorded. Open-loop disparity stimuli included steps, ramps, and sinusoids. It was found that the OL step and ramp responses to the central target were more rapid and exhibited significantly more step and multiple-step movements than those for either the peripheral or the central-plus-peripheral targets. During OL ramp stimulation, the maximum disparity for which tracking could be maintained was largest for the peripheral target. Sinusoidal responses showed the greatest gain for the central target. For all three types of stimuli, responses to the central-plus-peripheral target showed characteristics that were somewhat between those for the central and the peripheral targets. These results resolve some previously conflicting findings about open-loop vergence dynamics and suggest that large peripheral disparity stimulation initiates slow fusion of a visual scene, whereas small central disparity stimulation produces more rapid movements for precise binocular tracking of targets moving in depth. PMID- 1868904 TI - Branching patterns of the rat phrenic nerve during development and reinnervation. AB - Previous studies have shown that the phrenic motor nucleus in the rat projects onto the diaphragm muscle, forming an orderly topographic map. Moreover, this topography is partially restored upon reinnervation. This orderly map is expressed prior to birth, suggesting that early contacts between nerve and muscle are topographically appropriate. The phrenic divides during embryonic development into rostral and caudal branches, and motor axons preferentially enter the appropriate branch. In an effort to understand the mechanisms that underlie the choices growing phrenic neurons make in selecting their appropriate muscle targets, we examined the patterns of branching displayed by the phrenic nerve during development and reinnervation. In all muscles studied the phrenic nerve splits into three primary branches, rostral, caudal, and crural. At a coarse level the pattern of branching of the phrenic is remarkably consistent from animal to animal and at all ages of development. At a finer level of resolution, however, there is an asymmetry between right and left hemidiaphragms. Moreover, the precise emergence of any particular branch is unpredictable, resulting in an overall incongruence in branching architecture from animal to animal. The hemidiaphragm muscle grows unevenly, particularly on the right side, resulting in greater muscle fiber elongation medially. Upon reinnervation, the same coarse pattern of branching is reestablished, but the higher order pattern is much simpler and muscle growth is slower than in controls. These results suggest that very early in development primary branches of the phrenic funnel axons into three well-defined zones in the muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868905 TI - Induction of demyelination by intraneural injection of antibodies against sulfoglucuronyl paragloboside. AB - Sulfoglucuronyl glycolipids (SGGLs) carry the glucuronyl 3-sulfate (HNK-1) epitope which is recognized by monoclonal IgM paraproteins from patients with demyelinating polyneuropathy. We report that intraneural injections of rat anti SGGL antibodies induce demyelination in rat sciatic nerve, along with mild to moderate clinical symptoms. Morphologically, vesiculation and loosening of the myelin sheath were observed 3 h postinjection, followed by extensive demyelination and macrophage infiltration after 4 days. Since the anti-SGGL antibodies showed no cross-reactivity with other components in rat sciatic nerve, these results indicate that SGGLs alone can serve as the target antigens in demyelinating neuropathy. PMID- 1868906 TI - Differential and sex-specific effects of kainic acid and domoic acid lesions in the lateral septal area of rats on immune function and body weight regulation. AB - The lateral septal area (LSA) has been implicated in the control of various psychoneuroendocrine processes in the rat. Interactions between the endocrine and immune systems and sex differences in immunity reflect the interdependence of the immune and neuroendocrine systems. Kainic acid (KA) lesions in the lateral septal area not only modify neuroendocrine processes, but also produce a suppression of humoral immunity in female rats. Presently, we have evaluated the effects of neurotoxic lesions in the LSA on the humoral immune response and body weight regulation of male and female rats. Bilateral lesions in the LSA of adult male and female rats were produced by stereotaxically infusing either 0.25 microliters of kainic acid (1.5 micrograms/microliters) or 0.5 microliters of domoic acid (DA; 0.3 micrograms/microliters) into the LSA. In an additional study, LSA lesions using 0.25 microliters of DA (0.6 micrograms/microliters) were produced in female rats only. Sham operations consisted of bilateral injections of 0.9% saline into the LSA. The effects of these lesions on antibody production, following immunization with 100 micrograms ovalbumin in complete Freund's adjuvant, were examined. Blood samples were collected on Days 7 and 14 following immunization. The anti-ovalbumin IgM and IgG antibody titers were measured by an enzyme amplified ELISA assay. As found previously, KA-induced LSA lesions in adult female rats produced an increase in body weight and a suppression of the humoral immune response. However, LSA lesions produced with the neurotoxin DA had a similar effect on body weight but had no effect on humoral immunity. In male rats, neither body weight regulation nor the humoral immune response was affected by KA or DA lesions in the LSA. These results indicate that the effects of neurotoxic LSA lesions on body weight regulation and the humoral immune response are sex specific and further demonstrate that two closely related kainate neurotoxins have differential effects on the humoral immune response, but have similar effects on body weight regulation. Thus, neurons in the LSA of female rats that are involved in the inhibitory control of body weight are susceptible to both KA and DA, whereas neurons in the LSA associated with immunoregulation are differentially affected by KA and DA. Of further interest, a sex difference in DA susceptibility was noted, with male rats showing greater cell loss in the LSA following DA infusions, as compared to female rats. PMID- 1868907 TI - Adult rat barrel cortex plasticity occurs at 1 week but not at 1 day after vibrissectomy as demonstrated by the 2-deoxyglucose method. AB - Stimulation of a single facial vibrissa in rats receiving [14C]2-deoxyglucose leads to increased local cerebral glucose utilization in the corresponding contralateral barrel of lamina IV of the first somatosensory cortex (SmI). In the adult rat, the metabolic representation of such a barrel enlarges 2 months after removal of all other vibrissal follicles but enlargement is prevented by prior removal of SmI norepinephrine. Here, the early time course of such enlargement and how this was affected by cortical norepinephrine manipulations were examined in adult rats. One day after total vibrissal follicle removal with sparing of the central (C3) vibrissa, neither the areal extent nor absolute glucose utilization in the stimulated, spared C3 cortical barrel were changed. However, 7 days after follicle removal, the spared C3 barrel was enlarged by 41%, although absolute glucose utilization remained constant. This delayed onset of enlargement is compatible with either a structural or neurochemical change in barrel circuitry following vibrissal deafferentation. With ipsilateral locus coeruleus lesions but intact vibrissae, there was progressive enlargement of stimulated C3 barrel areas with increasing cortical norepinephrine depletion (r = 0.864) suggesting a suppressive effect of norepinephrine on activity spread in barrels with intact vibrissal afferents. Previously shown blockade of chronic (2 month) vibrissectomy induced barrel enlargement by norephinephrine depletion suggested an additional effect on plasticity. Even though acute (1 day) follicle removal here produced no change in spared C3 barrel area, addition of norepinephrine depletion produced a surprising 40% decrease in barrel area. Thus, barrel plasticity assessed by 2 deoxyglucose reflects a complex interaction between barrel metabolic activity and the extent of vibrissal and noradrenergic afferent input. PMID- 1868908 TI - Effects of applied currents on epileptiform bursts in vitro. AB - In this study, results show that applied electric currents can be effective to control the neuronal bursting that characterizes epileptic activity. Recordings from the CA1 region of rat hippocampus treated with penicillin show that local inhibition of epileptiform bursts is possible by short anodic current pulses (50 ms duration) applied extracellularly. Inhibition was evidenced by a large reduction (greater than 90%) in the amplitude of field potential. Data collected from 20 slices with moderate field potentials (50-80% of maximum) showed that current needed for complete inhibition was on the order of 42 +/- 3 microA. Intracellular recordings in CA1 cells (n = 13) showed that the decrease in field potential amplitude was accompanied by suppression of intracellular neuronal firing caused by somatic hyperpolarization as measured by transmembrane potentials. The resulting hyperpolarization was on the order of 13 mv below resting potential for weakly epileptiform responses (less than 50% of maximum response), and 50 mv below resting potential for strongly epileptiform activity (greater than 50% of maximum response). These results reveal the existence of a stimulation window within which inhibition of neuronal elements can be achieved without simultaneous excitation. PMID- 1868909 TI - Loss of AChE- and NGFr-labeling precedes neuronal death of axotomized septal diagonal band neurons: reversal by intraventricular NGF infusion. AB - The time course of cellular changes in the medial septum (MS) and vertical limb of the diagonal band area (VDB) after a complete unilateral fimbria-fornix (FF) transection has been studied using prelabeling of the septohippocampal neurons by bilateral hippocampal injections of the fluorescent retrograde tracer Fluoro-Gold (FG), in combination with acetylcholine esterase (AChE) histochemistry and nerve growth factor receptor (NGFr) immunocytochemistry. The results show that the long term disappearance of AChE-positive and NGFr-positive cells represents a combination of down-regulation of the marker proteins, cell shrinkage, and an actual cell loss. By 4 weeks after lesion the loss of FG-prelabeled cells amounted to 50% in MS and 30% in VDB. A further 25-30% of the MS neurons survived (as indicated by the presence of FG label), but were undetectable by the AChE and NGFr markers. Down-regulation of the marker proteins and cell shrinkage preceded the cell loss by more than a week: while shrinkage and reduced numbers of AChE/NGFr positive cells was evident already by 4-7 days, an actual cell loss (i.e., loss of FG-prelabeled cells) became evident only at 4 weeks after lesion. Continuous intraventricular NGF infusion (0.15 micrograms/day) was capable of counteracting all three types of changes. Infusion over 2 weeks reversed both atrophy and loss of AChE/NGFr staining, whereas infusion over 4 weeks completely prevented the later occurring cell loss. In addition, the NGF infusions induced significant hypertrophy in the undamaged cholinergic neurons in both nucleus basalis and striatum. It is concluded that down-regulation of marker proteins, such as AChE and NGFr, and cellular atrophy precede cell death in the axotomized septohippocampal system and that about 1/3 of the axotomized septal cholinergic neurons may survive for a long time in a down-regulated atrophic state. Exogenous NGF can prevent both the atrophic and the degenerative processes. PMID- 1868910 TI - Congenital haemolytic anaemia in a low birth weight infant due to congenital stomatocytosis. AB - A baby girl born at 31 weeks gestation showed severe haemolytic anaemia and hyperbilirubinaemia which led to exchange transfusion within the first 12 hours of life. There was no blood group incompatibility between mother and child but there was a marked stomatocytosis of the baby's red blood cells. Family history revealed a congenital stomatocytosis in the mother. Biochemical characterization of the defect was performed. Phospholipid analysis of the erythrocyte membrane of mother and child showed an increase in phosphatidylserine with a compensatory decrease in phosphatidylcholine and phosphatidylethanolamine. SDS-electrophoresis showed multiple modifications of the protein pattern with a decrease in band 6, an increased content of band 4.1b, a slight decrease in band 7 and a clear change in the shape of the protein band 3 pattern. The results suggest that the basis of the observed abnormalities is a common defect in protein posttranslational modification, rather than multiple genetic defects in the synthesis of several proteins. Haematologic, biochemical and clinical course of the disease in this preterm infant are discussed. PMID- 1868911 TI - Serum cobalamins in the elderly: a longitudinal study of a representative population sample from age 70 to 81. AB - In a representative population sample (n = 973) born 1901-1902 and examined at the ages of 70, 75, 79, and 81, the change in serum cobalamins with increasing age was studied by trend analysis using values obtained in single individuals at all four examinations. In subsamples without definable disorders, the mean annual decline was: among men 3.4 pmol/l (p less than 0.05), among women 3.2 pmol/l (n.s.). The decline was possibly more pronounced among individuals with low and intermediate concentrations. The health-related lower reference limits (the 2.5 percentile values of subsamples without definable disorders) did not differ significantly between sexes and age groups, but low concentrations or ongoing cobalamin medication became more common with advancing age. The results indicate a slight fall in serum cobalamins between age 70 and 81 but do not call for age related lower reference limits. PMID- 1868912 TI - Cytogenetics of secondary myelodysplasia (sMDS) and acute nonlymphocytic leukemia (sANLL). AB - 76 cases of secondary myelodysplasia (sMDS) and acute non-lymphocytic leukemia (sANLL) were cytogenetically analyzed. Among the 36 sMDS patients, 13 (36%) had only normal karyotypes whereas 23 (64%) displayed clonal chromosomal abnormalities. The most common aberrations were -7, 5q-, -5, and +8. In 10 patients (43% of the cytogenetically aberrant cases), clones with only one anomaly, mostly 5q- or -7, were found. Of the 40 sANLL patients, normal karyotypes were detected in 10 (25%). Among the 30 (75%) abnormal cases, the most frequent aberrations were -7, -5, +8, 7q-, -17, and +21. 12 patients (40%) had clones with single abnormalities, most often -7. In 4 sANLL patients cytogenetically unrelated clones were detected. A survey of all previously published secondary hematologic neoplasias reveals that the most frequent abnormalities in sMDS are -7 (41%), 5q- (28%), and -5 (11%), followed by der(21q), +8, 7q-, der(12p), t(1;7), -12, -17, der(17p), der(3p), der(6p), and 18. Clones with single aberrations have been found in 45% of the cases and cytogenetically unrelated clones have been described in 6%. The most common abnormalities in sANLL are -7 (38%), 5q- (17%), -5 (15%), +8 (13%), and -17 (11%), followed by der(3q), der(11q), der(12p), -21, 7q-, -18, der(3p), der(17p), +21, der(21q), der(6p), and -16. 38% of the sANLL patients have had clones with only one aberration and 3% have had unrelated clones. The frequencies of these nonrandom abnormalities in sMDS and sANLL are thus remarkably similar - the only exception appears to be 5q-, which is more common in sMDS. Also the mean number of abnormalities per case is similar - 5.3 in sMDS and 5.6 in sANLL. When the incidences of characteristic cytogenetic abnormalities were correlated with the type of previous therapy, -7 was found to be more frequent in sMDS and sANLL patients who had been exposed to chemotherapy whereas 5q- was associated with previous exposure to ionizing radiation in sMDS patients. PMID- 1868913 TI - Occurrence and characteristics of hereditary spherocytosis in Algeria. AB - In a survey of more than 12,000 persons referred to a hematological outpatient clinic in Algiers, we estimated that the incidence of hereditary spherocytosis (HS) is 1/1000. Another 9 cases were found in nine of the corresponding families. Anemia was present in a total of 44 subjects (81%). The transmission was dominant in five of eight informative families (63%). No firm conclusion could be reached concerning the amount of spectrin and ankyrin in nine families; however two dimensional peptide maps ruled out any alphaII domain abnormality in these families. We estimate that HS has roughly the same incidence and features among Algerians as in Europeans or people of European descent. PMID- 1868915 TI - Vitamin B-12 abnormalities in HIV-infected patients. AB - A prospective study of 60 consecutively admitted patients with HIV infection was performed to document the prevalence, etiology and manifestations of low serum vitamin B-12 in such patients. Low serum B-12 levels were found in 10 patients (16.7%). In 6, vitamin B-12 absorption was impaired and hog intrinsic factor addition did not improve it. Patients with low vitamin B-12 levels showed lower hemoglobin, leukocytes, lymphocytes, CD4 lymphocytes and CD4/CD8 lymphocyte ratio than HIV patients with physiological serum vitamin B-12 levels. However, bone marrow megaloblastosis was found in only 3 low vitamin B-12 patients and the deoxyuridine suppression test was pathological in only 1 case. In 7 patients, parenteral treatment was begun with variable response despite serum vitamin B-12 correction. In conclusion, low serum vitamin B-12 is often found in HIV-infected patients and it could be related to malabsorption, but clear megaloblastic abnormalities and treatment response could not be demonstrated. A decreased concentration of the serum binders due to disturbances in the leukocytes and related immunocompetent cell may play an additional role. PMID- 1868914 TI - Inhibition of hexose monophosphate shunt in young erythrocytes by pyrimidine nucleotides in hereditary pyrimidine 5' nucleotidase deficiency. AB - Recent reports have suggested that haemolytic anaemia in pyrimidine 5' nucleotidase (P5'N) deficiency might be due to impaired erythrocyte hexose monophosphate shunt (HMS). To investigate the relationship between pyrimidine accumulation, HMS impairment and shortened red-cell survival, we tested glucose 6 phosphate dehydrogenase (G-6PD), HMS, P5'N activities and the UV spectrum in whole red cells and in red cells of different age from 2 P5'N-deficient patients with different degrees of haemolytic anaemia. In whole red cells we found a reduction of both G-6PD and stimulated HMS activity in the presence of a variable amount of pyrimidine nucleotides (37.79 and 17.88 mumol/gHb respectively). A drastic inhibition of stimulated HMS activity was already present in the lightest red-cell fractions from patient 1, who presented a more severe haemolytic anaemia. The variable degree of pyrimidines found among red cell fractions, with a minor accumulation in the older red cells, supports the hypothesis that pyrimidine accumulation and HMS impairment occur in the younger erythrocytes of P5'N-deficient patients. PMID- 1868916 TI - Growth response to cytokines of circulating myeloid progenitors from myelodysplastic patients at diagnosis and more than 600 days after diagnosis. AB - Myeloid colony growth from the peripheral blood of myelodysplastic (MDS) patients was assessed for abnormal in vitro response to haemopoietic growth factors (granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1), interleukin-3 (IL-3)). Abnormal colony growth, increased or reduced, was observed with each of the factors. No specific growth pattern was related to any of the French-American-British classification (FAB) types of disease. MDS patients who had survived greater than 600 days after diagnosis (n = 34) showed significantly fewer abnormalities than patients assayed at the time of diagnosis (n = 37), the major difference being less frequent stimulation of colony growth. These findings indicate that the time of sampling relative to diagnosis needs to be considered when interpreting the in vitro response to growth factors of myeloid colonies from MDS patients. PMID- 1868917 TI - Human neutrophil migration into skin chambers is associated with production of NAP-1/IL8 and C5a. AB - Respiratory burst activity initiated by the chemoattractants fMLP, rC5a and rNAP 1/IL8 was investigated in human exudated and peripheral blood neutrophils. Exudated cells were isolated after migration into a skin chamber and the respiratory burst activity was measured as chemiluminescence amplified by luminol and horseradish peroxidase. The response to fMLP (5 x 10(-8) mol/l) was significantly enhanced (p less than 0.01) in the exudated cells but was significantly decreased after stimulation (5 x 10(-8) mol/l) with rC5a and rNAP 1/IL8 (p less than 0.05 and p less than 0.01, respectively). Analysis revealed that, in the chamber fluid, the activated complement C5a was generated during exudation (p less than 0.01). Determinations of NAP-1/IL8 showed that this substance was also produced and released into the chamber fluid (p less than 0.01). No correlation was found between the number of exudated cells and the amount of C5a or NAP-1/IL8 in the exudation fluid, thus indicating that, in vivo, the exudation process is controlled by multiple factors and not by the quantity of a single chemoattractant. The present study shows that NAP-1/IL8 and C5a are produced in humans during an aseptic inflammation, and that this occurs in parallel to the migration of neutrophils into the skin chambers. The significant desensitization of the exudated cells to NAP-1/IL8 and C5a reflects a previous exposure to these attractants. These results suggest that the novel tissue derived cytokine NAP-1/IL8 plays a role in human neutrophil exudation in vivo. PMID- 1868918 TI - Effect of tranexamic acid on platelet function in normal volunteers. PMID- 1868919 TI - [Measurement of urinary epidermal growth factor by radioimmunoassay and its application]. AB - Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. Herein, radioimmunoassay (RIA) for human EGF (hEGF) has been developed, using human recombinant EGF as reference standard and radioiodinated tracer and antibodies raised against hEGF. Its sensitivity was somewhat higher than that of RIAs reported formerly. This method had no cross reactivity with high molecular weight EGF. Urinary concentrations of hEGF in normal males and females were 30.2 +/- 13.0 ng/mg creatinine and 46.4 +/- 17.4 ng/mg creatinine, respectively. Urinary concentration of hEGF in patients with renal cancer was somewhat low. The patients with bladder cancer had lower urinary excretion of hEGF than normal adults (p less than 0.05). However, the role of hEGF in health and disease remains to be determined. PMID- 1868920 TI - [GH-secretion capacity in Turner syndrome and its relations to clinical characteristics and effect of GH treatment--a comparison with pituitary dwarfism. The Committee for hGH treatment in Turner syndrome]. AB - The relations of GH secretion capacity by stimulation tests to clinical characteristics and the effect of GH treatment were studied in 151 girls with Turner syndrome and were compared with those in 128 patients with pituitary dwarfism. GH secretion capacity expressed by mean peak GH was not associated with clinical characteristics related to growth such as height SDS and growth velocity SDS in Turner syndrome and was influenced by % overweight, whereas it was associated with growth-related clinical characteristics in pituitary dwarfism. Because GH secretion capacity does not affect growth in Turner syndrome, it is not reasonable to diagnose low peak GH in stimulation tests as GH deficiency in Turner syndrome. GH treatment increased the growth velocity and growth velocity SD score in Turner syndrome in a dose-dependent manner. In pituitary dwarfism, the effect of GH treatment expressed by the increase in growth velocity SD score had a negative correlation with growth velocity SD score before GH treatment and GH secretion capacity, which indicated that GH treatment was replacement therapy. In Turner syndrome, the effect of GH treatment had a negative correlation with growth velocity and growth velocity SD score before GH treatment, but had no relation to GH secretion capacity, which suggested that GH treatment did not provide replacement GH but had another pharmacological effect. PMID- 1868921 TI - [Studies on the renal handling of urea nitrogen, creatinine, water and electrolytes in hyperthyroid patients with Graves' disease]. AB - To delineate the pathophysiological basis for increased blood urea nitrogen (BUN), decreased serum creatinine (SCr) and increased BUN/SCr ratio in patients with hyperthyroidism due to Graves' disease, systematic evaluation on renal handling of solutes and water was carried out before and during treatment of the disease. First, BUN, SCr, serum sodium (Na), serum potassium (K), serum chloride (Cl), creatine kinase (CK), serum triiodothyronine (T3) and serum thyroxine (T4) were consecutively measured in 16 patients (aged 18-62 yrs, 4 males and 12 females) with Graves' disease before and during antithyroid drug therapy, and 16 healthy subjects (aged 22-64 yrs, 4 males and 12 females) served as controls. BUN (14.8 +/- 2.9 mg/100ml) was significantly higher (p less than 0.01), and SCr (0.62 +/- 0.16 mg/100ml) and CK (41.7 +/- 23.6 U/l) were significantly lower (p less than 0.01) in untreated patients compared to respective values in the control group (BUN, 13.2 +/- 2.9 mg/100ml; SCr, 0.87 +/- 0.16 mg/100ml; CK, 99.3 +/- 49.5 U/l). Consequently, BUN/SCr ratio was significantly elevated (p less than 0.01) in the patients. As T4 and T3 returned to normal, BUN, SCr, BUN/SCr ratio and CK of the patients also normalized. Serum electrolytes were not significantly different in the patients compared to the controls. Second, renal clearance of para-aminohippurate (CPAH), inulin (CIn), creatinine (CCr), free water (CH2O) and chloride (CCl) was evaluated in 7 untreated patients (aged 17-44 yrs, 4 males and 3 females) and in 7 controls (aged 24-39 yrs, 5 males and 2 females). In patients with untreated Graves' disease, CPAH, CCr and Curea were significantly greater than in the controls (847 +/- 367 vs 442 +/- 124 ml/min, p less than 0.05, 132.7 +/- 14.7 vs 76.6 +/- 14.4 ml/min, p less than 0.01, and 86.9 +/- 16.0 ml/min vs 52.1 +/- 12.6 ml/min, p less than 0.05, respectively). CIn was slightly but insignificantly increased in the patients (95.3 +/- 20.8 ml/min) compared to the controls (76.7 +/- 13.3 ml/min). As a result, CCr/CIn and Curea/CIn were significantly greater in the patients than in the controls (142.7 +/- 32.0 vs 100.7 +/- 7.1%, p less than 0.01, 92.4 +/- 18.7 vs 68.4 +/- 14.4%, p less than 0.05, respectively). The difference between CCr and CIn indicates that 40% of urinary creatinine is of tubular origin. Renal excretion of urea and creatinine was increased by 117% and decreased by 77%, respectively in the patients, but the differences were not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1868922 TI - [The effects on the thyroid gland of soybeans administered experimentally in healthy subjects]. AB - To elucidate whether soybeans would suppress the thyroid function in healthy adults, we selected 37 subjects who had never had goiters or serum antithyroid antibodies. They were given 30g of soybeans everyday and were divided into 3 groups subject to age and duration of soybean administration. In group 1, 20 subjects were given soybeans for 1 month. Groups 2 and 3 were composed of 7 younger subjects (mean 29 y.o.) and 10 elder subjects (mean 61 y.o.) respectively, and the subjects belonging to these groups received soybeans for 3 months. The Wilcoxon-test and t-test were used in the statistical analyses. In all groups, the various parameters of serum thyroid hormones remained unchanged by taking soybeans, however TSH levels rose significantly although they stayed within normal ranges. The TSH response after TRH stimulation in group 3 revealed a more significant increase than that in group 2, although inorganic iodide levels were lowered during the administration of the soybeans. We have not obtained any significant correlation between serum inorganic iodide and TSH. Hypometabolic symptoms (malaise, constipation, sleepiness) and goiters appeared in half the subjects in groups 2 and 3 after taking soybeans for 3 months, but they disappeared 1 month after the cessation of soybean ingestion. These findings suggested that excessive soybean ingestion for a certain duration might suppress thyroid function and cause goiters in healthy people, especially elderly subjects. PMID- 1868924 TI - [Dependency of estramustine binding protein (EMBP) from rat prostate to endogenous androgen]. AB - In this study, we investigated the dependency of estramustine binding protein (EMBP) from rat prostate on endogenous androgen. The EMBP content of the dorsolateral prostate markedly decreased 14 days after castration and increased again after the cessation of the weekly subcutaneous administration of 2 mg of Estradiol-17 beta valerate, in accordance with the recovery of prostate weight and serum testosterone concentration. This result clearly demonstrated that EMBP, which was present in very small quantities in the dorsolateral prostate, had a dependency on endogenous androgen as well as on the ventral prostate EMBP. We investigated the changes in prostate weights, EMBP concentration and serum testosterone level throughout life. The ventral prostate weight began to increase rapidly at 7 weeks of age and showed a broad peak from 11 to 14 weeks of age and then gradually decreased. On the other hand, the dorsolateral prostate weight began to increase rapidly at 7 weeks of age and continued to increase very gradually even after 10 weeks of age. There was a remarkable difference in the changes in EMBP concentration between the ventral prostate and the dorsolateral prostate. In the ventral prostate, EMBP concentration increased markedly from 4 to 9 week of age. Thereafter it continued to increase very gradually. On the other hand, in the case of the dorsolateral prostate, EMBP demonstrated higher and fluctuating concentration from 4 to 15 weeks of age. After 16 weeks of age, EMBP showed lower and stable concentration, although the weight of dorsolateral prostate showed gradual increase. These results suggested that there exist, beside androgens, some factors that participated in the regulation of growth and functional metabolism in the dorsolateral prostate after 16 weeks of age. PMID- 1868923 TI - [The effect of maternal IGF-I on fetal and placental growth in mice]. AB - Insulin-like growth factor-I (IGF-I) is a polypeptide that mediates growth promoting actions of GH and has insulin-like activity. Increase in the levels of IGF-I in the maternal and fetal circulation during pregnancy and the identification of the specific receptors for IGF-I in a variety of fetal tissues suggest that IGF-I may play a significant role in the regulation of fetal growth. The present study was undertaken to determine the significance of maternal IGF-I on fetal and placental growth by administering the specific antiserum for IGF-I to pregnant mice. The antiserum was produced by repeatedly injecting recombinant IGF-I into rabbits. The antiserum obtained showed 30% binding to 125I-IGF-I at a dilution of 1:240,000, and crossreactivity with IGF-II was 0.012%. In the first set of experiments, pregnant mice were given a daily dose of 50 microliters of the original antiserum (E-1) or normal rabbit serum (C-1) into the peritoneal cavity between Day 3 and 10. In the second set of experiments, antiserum (E-2) or normal rabbit serum (C-2) was administered between Day 11 and 18. On Day 18, all mice were killed, blood was collected for measurement of levels of IGF-I by RIA, and the weights of fetuses and placentas in individual mice were recorded. The maternal levels of IGF-I in group E-1 and E-2 were extremely low compared to those in group C-1 and C-2. The number of fetuses and rate of abortion among each group were not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868925 TI - Safety evaluation of substances consumed as technical ingredients (food additives). AB - The different types of acceptable daily intakes (ADIs) are described as used by the FAO/WHO Expert Committee on Food Additives (JECFA) and the EEC Scientific Committee for Food (SCF). The allocation is discussed of a full ADI or a temporary ADI, and examples are given for the establishment (or withdrawal) of these ADIs. The flavours cinnamyl anthranillate and the solvent 2-nitropropane (both withdrawn), the sweeteners cyclamate and saccharin and the antioxidant BHA (all three changed) but not abolished. For BHA and saccharin the ADI was retained by both committees in spite of some evidence of carcinogenicity to experimental animals. ADI--'not specified' is specially discussed and it is recommended that numerical ADIs are used whenever possible. With an ADI--'not specified' it should be stated which use (and intake) levels are toxicologically acceptable. Some compounds evaluated by the two committees are discussed, e.g. the colours: Allura red AC, erythrosine, canthaxanthin and the caramels; three anti-oxidants: BHA, BHT and the gallates; the sweeteners: polyols, aspartame, saccharin and cyclamates. Four recommendations are made: (1) a numerical basis be given for the levels allocated an ADI--'not specified' or 'acceptable'; (2) lowering of the conventional safety factor be considered when the effects found are trivial- higher safety factors be considered when the toxic effects are serious or even irreversible; (3) ADIs should, whenever possible, be based on a combination of human and animal data; (4) ADIs might be allocated to compounds indicating animal carcinogenicity, if the compound is non-genotoxic, the mechanism clearly secondary and/or species-specific. PMID- 1868926 TI - Safety factors and establishment of acceptable daily intakes. AB - The acceptable daily intake (ADI) of food additives and other foreign compounds is derived usually by the application of a 100-fold safety factor to the 'no observable adverse effect' level in animal experiments. This safety factor is recognized as comprising two 10-fold factors to allow for possible differences between animals and humans, and for possible differences between individual humans. This paper reviews the adequacy of these safety factors in relation to published data on inter-species and inter-individual differences in both the kinetics and dynamics of foreign compounds. Although the 100-fold factor is reasonable, situations can be envisaged where the scientific data base indicates that considerably higher or lower factors would be more appropriate. A scheme is proposed that would allow structured flexibility to be available in the choice of safety factor to be used in the regulation of foreign compounds. PMID- 1868927 TI - The concept of the acceptable daily intake: an historical review. AB - In the first section the sequence of events is outlined which leads to the author's proposal to consider the concept of acceptable daily intake (ADI) for pesticide residues. He developed his theory referring to specific aspects during meetings with experts on the toxicological evaluation of chemical agents which become introduced into foodstuffs intentionally or unintentionally. These meetings were organized periodically by the European Council or Joint FAO/WHO Expert Committees on food additives (JECFA) or pesticide residues (JMPR). The general principles of the ADI evaluation are briefly described as being based on the determination (after extended absorption) of a no-effect dose level in an appropriate animal species; followed by the application, for the extrapolation of the results in animals to humans, of safety factors taking into account the interspecies sensitivity variations and individual sensitivity variations in the groups of essentially heterogeneous human consumers. It is pointed out that the ADI value, which depends on a series of factors, is not a constant, but a guide serving to calculate the admissible limits of diverse chemical agents incorporated in foodstuffs. It must take into account the usual normalities between medium terms of consumption varying a lot with the countries and the various consumer groups. It is clearly noted that, because of the fluctuations in the type and the quantities of absorbed diets, the ADI is in reality an integrated value with regard to the time, a notion that is often forgotten. Other ideas are developed, in particular on the adoption of a temporary ADI and on the concept of a non-specified ADI. PMID- 1868928 TI - Contents of Fusarium toxins in Finnish and imported grains and feeds. AB - The aim of the present study was to investigate the levels of trichothecenes in representative samples of Finnish and imported cereals and feeds from the 1987 and 1988 crops. Trichothecene concentrations were determined in samples as trimethylsilylether derivatives by a gas chromatograph equipped with a mass selective detector (GC-MSD) using selected ion monitoring (SIM) which proved to be a reliable and sufficiently sensitive technique. Representative samples of Finnish and imported oats, wheat, barley, rye, maize gluten, soy granules, rapeseed, turnip rapeseed, fish meal, poultry feed and pig feed were analysed employing 19-nortestosterone as an internal standard. Almost all grain and feed samples contained deoxynivalenol (DON) from 7 to 300 micrograms/kg and smaller amounts (13-120 micrograms/kg) of 3-acetyldeoxynivalenol (3-AcDON). The most toxic trichothecenes, T-2, HT-2 toxins and nivalenol (NIV) and also zeralenone (ZEN) were found at low concentrations in some samples. Six lots of oats containing 1.3-2.6 mg/kg of DON and 0.2-0.6 mg/kg of 3-AcDON were found in the Finnish grain samples. Silo samples of almost all imported grains contained DON but at levels below 50 micrograms/kg. Imported grains contained no other trichothecenes. DON, 3-AcDON and ZEN were found in imported feedstuffs at low concentrations. PMID- 1868929 TI - Plasma ochratoxin A levels in three Swedish populations surveyed using an ion pair HPLC technique. AB - A new HPLC method for the analysis of ochratoxin A in plasma samples is described. The analysis is performed at an alkaline pH using an ion-pair technique, fluorescence detection at an excitation wavelength 380 nm, and an emission wavelength 420 nm. The detection and quantification limits are 0.02 ng and 0.05 ng ochratoxin A/ml plasma, respectively. The method was used to determine the ochratoxin A content of human plasma samples, collected in three districts of Sweden. The Visby district had a significantly higher proportion of ochratoxin A positive samples and higher levels than the other two districts- Uppsala and Ostersund. The calculated daily intake of ochratoxin A in the Visby district (0.35 ng/kg body weight), exceeds the lower tolerable daily intake (TDI) value suggested by Kuiper-Goodman and Scott (1989). The calculated daily intake by the population on the mainland of Sweden (0.04 ng/kg body weight) is below the proposed TDIs. PMID- 1868930 TI - Preliminary studies on the bioavailability and disposition of bioincurred carrot residues of [14C] linuron and [14C]3,4-dichloroaniline in rats. AB - Carrots grown from seed in soils spiked with [14C = O]linuron or [14C-ring]3,4 dichloroaniline (DCA), were found to contain radioactivity equivalent to 0.73 ppm linuron or 0.60 ppm DCA. After exhaustive extraction with methanol these tubers still retained 35% and 67% of the original 14C-bioincurred residues, for linuron and DCA respectively. To examine the bioavailability of these residues, rats were dosed by gavage (water vehicle) with unextracted tubers and extracted tubers. For comparison purposes 14C-spiked carrot tubers and [14C] standards were also administered. Animals were maintained for 3 days in metabolism cages; urine, faeces, expired gases and several tissues were collected for radioassay. The following relative amounts of radioactivity (expressed as a percentage of the applied dose) were excreted (faeces/urine) for linuron or DCA dosing respectively: unextracted carrots, 28/31, 51/10; extracted carrots, 51/0, 73/3; spiked carrots, 11/43, 63/20; and linuron and DCA standards, 11/46, 26/81. The data demonstrated that approximately 31% and 10% of bioincurred 14C-residues (from linuron and DCA respectively) in unextracted carrot tubers were bioavailable to rats. 14C-Bound residues (extracted tubers) were much less bioavailable (0% and 3% respectively). The disposition of radioactivity in tissues, blood and expired gases was very low (less than or equal to 1.3% per sample) for any dose studied. PMID- 1868931 TI - Lead, cadmium, arsenic and mercury in meat, liver and kidney of Swedish pigs and cattle in 1984-88. AB - During the period 1984-88 several hundred samples of meat, liver and kidney from Swedish pigs and cattle were analysed for lead, cadmium, arsenic and mercury. Analysis was performed by AAS and extensive quality assurance was carried out. The mean lead levels in pig meat, liver and kidney were less than 0.005, 0.019 and 0.016 mg/kg, respectively: the mean levels in the corresponding bovine tissues were less than 0.005, 0.047 and 0.097 mg/kg. The mean cadmium levels in pig meat, liver and kidney were 0.001, 0.019 and 0.11 mg/kg, whilst those in the corresponding bovine tissues were 0.001, 0.070 and 0.39 mg/kg. The mean arsenic levels in pig meat, liver and kidney were 0.024, 0.023 and 0.019, respectively and those in the corresponding bovine tissues were lower, none exceeding 0.015 mg/kg. The mean mercury levels in pig meat, liver and kidney were 0.009, 0.015 and 0.019 mg/kg respectively, while those in the corresponding bovine tissues were 0.005, 0.006 and 0.010 mg/kg. A decrease in the levels of both arsenic and mercury in pig tissues was found during the period studied, which may be due to a decrease in the use of fish meal in pig feed. PMID- 1868933 TI - Introduction of methods in epidemiologic studies with reference of cataract. PMID- 1868932 TI - Rationales for the establishment of limits and regulations for mycotoxins. AB - Although 50 countries have enacted or proposed regulations for control of alfatoxins in food or feed, and 15 of these countries also have regulations for permitted levels of contamination by other mycotoxins, very few countries have formally presented the rationale for the need to regulate, or for the selection of a particular maximum tolerated level. After several successive inquiries, information concerning the rationale for regulation was obtained from 21 countries. Most of the responses concerned limits for aflatoxin in food, and most of these were based on a vague, unsupported statement of the carcinogenic risk for humans. There was a general consensus that exposure to a potential human carcinogen that could not be totally avoided should be limited to the lowest practical level; the definition of practicality depended on whether the country was an importer or producer of the potentially contaminated commodity. A claim to a hazard evaluation was made by six countries (Canada, Belgium, India, United Kingdom, United States, Switzerland) without providing specifics; and one country, South Africa, referred to a risk determination. The most comprehensive rationale for any mycotoxin regulation was provided by the United States in support of limits for aflatoxin in specific animal feedstuffs. The responses provided no rationale for setting limits for other mycotoxins; but scholarly risk assessments for zearalenone and ochratoxin A have been published by Canadian government scientists, and a symposium presentation provides the information that in Norway patulin is regulated for quality control purposes only. It is apparent that, in most countries, either the scientific basis for regulation of mycotoxins is nonexistent, or the science has not been fully utilized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868934 TI - Practical cataract classification for epidemiological studies. PMID- 1868935 TI - Interview form applied to a cataract epidemiologic study. Japanese Cooperative Cataract Epidemiology Study Group. PMID- 1868936 TI - Contribution to the improvement of epidemiological cataract classification. PMID- 1868937 TI - Evaluation of risk factors in human cataractogenesis. PMID- 1868938 TI - Discrepancy between onset of early lens changes and onset of senile cataract: the case for cellular defense systems in the human eye lens. PMID- 1868939 TI - Lipid analysis in defined bovine lens slices. PMID- 1868940 TI - Protein profiles after UV-B irradiation and bendazac lysine (bendalina) treatment. PMID- 1868942 TI - Oxygen and light as risk factors in senile cataract development: experimental studies. PMID- 1868941 TI - Singlet oxygen chemiluminescence quenching in the NaClO + H2O2 reaction in the presence of anticataract drugs. PMID- 1868943 TI - Current cataract epidemiology studies in Japan. PMID- 1868944 TI - Epidemiology of cataract in outpatient clinics. PMID- 1868945 TI - Epidemiological study on cataract in Bulgaria. PMID- 1868946 TI - Prevalence of age-related cataract in Ganzi and in Qinpu. The Epidemiological Study Group. PMID- 1868947 TI - Epidemiological study for cataract in a northern area of Japan. Cataract and its subjective symptom. PMID- 1868948 TI - A retrospective study of cataract among Arabs residing in Kuwait. PMID- 1868949 TI - Prevalence of lens opacities in a population-based survey in Sofia District: a preliminary report. PMID- 1868951 TI - Risk factors in cataract development: a review. PMID- 1868950 TI - The control and prevention of cataract in West Sumatra, Indonesia: the pattern of some types of cataract in coastal and suburban areas. PMID- 1868952 TI - Common risk factors in the development of cataract among Arabs residing in Kuwait. PMID- 1868953 TI - Risk factor diabetes: long-term follow-up Scheimpflug slit image analysis of lens transparency of diabetic patients. PMID- 1868954 TI - Risk factor analysis in a cataract epidemiological survey in West Sumatra, Indonesia. PMID- 1868955 TI - The risk factors of developing cataract in patients with uveitis. PMID- 1868956 TI - Investigation of cataract risk factors with retro-illumination photography II. PMID- 1868957 TI - Cataract classification systems in epidemiological studies. PMID- 1868958 TI - [A multifactorial etiologic approach to diabetic dyschromatopsia. Study of 100 diabetics]. AB - Diabetic dyschromatopsia is frequent and is a true complication of diabetes mellitus. Causative factors other than retinopathy have been suggested, but they remain unclear. We have explored the color vision of 100 diabetics aged 16 to 65 (88 insulin-dependent, 12 non-insulin dependent) with Lanthony's D15 desatured panel. Degenerative complications were looked for, especially by fundoscopy and electrophysiological exploration of peripheral nerves using specific scoring. 73% of the diabetics had dyschromatopsia. Dyschromatopsia was significatively more frequent when retinopathy was present (26 out of 30 diabetics with retinopathy versus 47/70 without). We explain the absence of a strict parallelism between dyschromatopsia and retinopathy by the intervention of other factors. Whereas the equilibration of the diabetes was not different between the groups with or without dyschromatopsia, patient age, microalbuminuria, blood pressure and alcohol intake were higher in patients with dyschromatopsia. The greater prevalence of peripheral neuropathy in patients with dyschromatopsia, confirmed by electrophysiology, and independently from the existence of retinopathy, is an indicator of the existence of neuronal disease, whose level remains to be determined. Our results are the indispensible preliminary step to a study of the respective importance of these pathogenic factors. PMID- 1868959 TI - Lipoprotein lipase in experimental diabetic rats: beneficial effect of vanadate treatment. AB - Elevated values of circulating triglycerides were observed in streptozotocin hyperglycemic rat while cholesterol concentrations did not differ from controls. Daily oral administration of sodium metavanadate to these diabetic animals normalized blood glucose values without raising the reduced levels of insulin. Concomitant with the normalization of the glycemia, the elevated triglyceride values found in diabetic rats were also corrected. Lipoprotein lipase activity in adipose and cardiac tissues was significantly decreased in the streptozotocin diabetic animals. Similarly, the hepatic lipase activity was also depressed. After vanadate treatment, lipoprotein lipase as well as hepatic lipase activities were corrected towards normal values. Thus, vanadate treatment of streptozotocin diabetic animals induces normalization of blood glucose and triglycerides levels, while maintaining low amounts of circulating insulin. It also restores the depressed activities of adipose and cardiac lipoprotein lipase and hepatic lipase. PMID- 1868960 TI - Premixed insulin at ratio 3/7 and regular + isophane insulins at mixing ratios from 2/8 to 4/6 achieve the same metabolic control. AB - The insulin regimen with two daily injections is still that more frequently used. Often regular and NPH insulins are mixed at different ratios according to the patient's need; however, the mixture preparation can involve several errors. Efficacy, safety and compliance were evaluated comparing a premixture 3/7 (Actraphane HM) with extemporary mixtures of regular + NPH at mixing ratios ranging from 2/8 to 4/6, in a cross-over study of 8 weeks involving 20 insulin dependent diabetics. Metabolic control, hypoglycaemic episodes, insulin dose and proportions were similar with both treatments while a higher compliance was achieved with the premixture. In conclusion, premixture 3/7 and extemporary mixture (from 2/8 to 4/6) obtain the same efficacy and safety but the former shows a higher acceptability. PMID- 1868961 TI - Effects of counterregulatory hormones on insulin-induced glucose utilization by individual tissues in rats. AB - The effect of counterregulatory hormones (epinephrine, norepinephrine and glucocorticoids) on insulin-induced glucose utilization in individual tissues of normal rats was investigated in vivo. This was done in normoglycaemic conditions, using the euglycaemic hyperinsulinaemic clamp combined with an injection of 2-[1 3H]-deoxyglucose. The main effect of these hormones was to reduce insulin-induced glucose utilization in skeletal muscles and particularly in the oxidative one. No changes were observed in heart diaphragm and adipose tissues. These results emphazise the role of counterregulatory hormones on glucose utilization and demonstrate that muscles are their major site of action. They support the notion that the increase in plasma concentrations of these hormones could play a role in states of insulin resistance like obesity and diabetes. PMID- 1868962 TI - [Impact of diabetes mellitus on driving safety]. AB - Driving ability is controlled by specific regulations. Therefore disabled individuals or those with certain chronic diseases may be affected by these regulations. These latter are based on assumption that the existence and the nature of certain diseases may cause particular hazard; and this could be prevented by introducing certain driving regulations. This hypothesis has not been tested properly, considering the proposed and suspected risk factors. Diabetes mellitus is a good example of the interested medical condition in this field. Review of the literature do not provide adequate information to allow us to conclude whether the insulin treated diabetic person is at higher risk to develop traffic accident, compared with non diabetic individual; and there is no definite explanation whether hypoglycaemia play a causative role in the etiology of traffic accident among insulin treated diabetics. Perhaps the lack of knowledge in this field is due to use of non-standardized methodologies and small sample size studies which make the comparisons difficult. The existing regulations in different countries are based on empirical knowledge and common sense. This often leads to conflictual situations and apparently discriminatory decisions regarding diabetics. Further comparative and prospective studies are needed. PMID- 1868963 TI - Decreased insulin response to glucose in sickle cell trait. PMID- 1868964 TI - Sialic acid content in the erythrocyte membrane of diabetics. PMID- 1868965 TI - Relaxant effects of oxytocin and 8-l-lysine-vasopressin on guinea pig and human gallbladder strips in vitro contracted by histamine. AB - Both human and guinea pig gallbladder strips were tonically contracted by supramaximal concentrations of histamine in vitro. Guinea pig gallbladder strips were also tonically contracted by potassium, with no spontaneous relaxation after 5 min. The amplitude of the contractions caused by histamine decreased spontaneously only by 34 +/- (SD) 10% after 5 min in guinea pig strips and by 25 +/- 7% after 5 min in human strips. Both oxytocin and 8-l-lysine-vasopressin dose dependently relaxed almost completely contractions caused by histamine and potassium in guinea pigs. In humans, only 8-l-lysine-vasopressin decreased the amplitude of histamine contractions. In both species, neither oxytocin nor 8-l lysine-vasopressin affected the basal tone of strips. PMID- 1868966 TI - Changes in gastric mucosal content of adenosine, xanthine and hypoxanthine induced by restrained water immersion stress: antiulcer effects of tetraprenylacetone. AB - The purpose of this study was to clarify the involvement of adenine nucleotide metabolism and substrates of the xanthine-xanthine oxidase system as the source of oxygen free radicals in a rat model of restrained water immersion stress ulceration. The gastric mucosal concentrations of adenine-5'-triphosphate (ATP), adenine-5'-diphosphate (ADP), adenine-5'-monophosphate (AMP) and thiobarbituric acid (TBA)-reactant substances were measured after 4, 8 and 12 h restrained water immersion stress. The gastric mucosal concentrations of the nucleoside adenosine, the purine bases xanthine and hypoxanthine, and the final metabolic product uric acid, were measured after 4 h of restrained water immersion stress. The concentrations of ATP diminished significantly after 4, 8 and 12 h of restrained water immersion stress. However, the observed stress-induced changes in ADP were not significant. AMP concentrations increased significantly after 4, 8 and 12 h of stress. The adenylate pool (ATP + ADP + AMP) dropped significantly from the prestress value after 4, 8 and 12 h of stress, and the concomitant energy charge (EC = ATP + 0.5 ADP/ATP + ADP + AMP) decreased significantly after 4 and 8 h of stress compared with the prestress value. Gastric mucosal concentrations of TBA reactant substances displayed a significant increase after 4 h of stress, and remained unchanged after 8 and 12 h of stress from the level after 4 h. Four hours of restrained water immersion stress induced an increase in adenosine and uric acid concentrations and a decrease in the hypoxanthine concentration of the gastric mucosa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1868967 TI - Influence of the M1-receptor antagonists telenzepine and pirenzepine on pancreatic secretory response to intraduodenal tryptophan in dogs. AB - In conscious dogs with gastric and pancreatic fistulas, we compared the action of different doses of telenzepine (ranging from 9 to 243 nmol kg-1 h-1 i.v.) and pirenzepine (ranging from 43 to 1,170 nmol kg-1 h-1 i.v.) on the pancreatic secretory response to graded loads of intraduodenal infusions of tryptophan, given with a secretin background. Both, telenzepine and pirenzepine caused an overall significant inhibition of the cumulative incremental pancreatic protein output by 65.8 and 66.8%, respectively. The pancreatic bicarbonate output was also reduced by 38.3 and 40.5%, respectively, but the effect did not reach statistical significance. The inhibitory potency of the effective doses of telenzepine or pirenzepine did not differ significantly. Only the highest doses of telenzepine (243 nmol kg-1 h-1 i.v.) and of pirenzepine (1,170 nmol kg-1 h-1 i.v.) significantly increased heart rate from 59.9 +/- 3.4 to 63.1 +/- 4.5 bpm, respectively. These findings indicate that (1) in the intact animal, the M1 receptor antagonists telenzepine and pirenzepine are capable of inhibiting pancreatic bicarbonate and protein output in response to intraduodenal tryptophan with secretin background, and (2) telenzepine is 4.7 times more potent than pirenzepine. PMID- 1868968 TI - Idiopathic oligofecorrhea: a clinicopathologic entity--pathogenesis and treatment. AB - Oligofecorrhea is the term applied for infrequent defecation (2 or less stools per week). 146 patients with oligofecorrhea were studied. Investigations comprised radiologic, endoscopic, intestinal transit and rectal pressure studies. EMG for levator and sphincteric muscles as well as internal sphincter biopsy were done. The 146 patients could be categorized into 3 stages according to clinical and investigative results. However, the 3 stages share major abnormal findings which comprise high resting rectal neck pressure, reduced or absent recto inhibitory reflex, internal sphincter hypertrophy and degeneration of the nerve plexus of the internal sphincter. A new theory of pathogenesis of oligofecorrhea is put forward. It is believed that innervation abnormalities of the internal sphincter interferes with the recto-inhibitory reflex action with a resulting failure of the internal sphincter to relax upon rectal distension. It seems that the degenerative changes of the nerve plexus affect mainly the parasympathetic supply leading to sympathetic overactivity. The latter leads to abnormal internal sphincter contraction which eventually results in muscle hypertrophy. Internal sphincter myotomy showed a mean improvement of 90.4% in all the cases. The stool frequency and rectal neck pressure were normalized. PMID- 1868969 TI - Intravenous omeprazole in upper gastrointestinal haemorrhage in critically ill patients. PMID- 1868971 TI - Measurement of anal cross-sectional area and pressure during anal distension in healthy volunteers. AB - A probe for simultaneous measurement of cross-sectional area and pressure was used to elucidate biomechanical wall properties during anal distension. Measurements in distal sphincter regions demonstrated a high resistance to stretch and a large hysteresis compared to proximal sphincter regions. Resistance to stretch decreased during anal distension indicating an active relaxation mechanism at all recording levels. The zone with high resistance to stretch was located more distal than the high-pressure zone measured by anal-pressure profilometry. In conclusion, biomechanical wall properties of the anal canal cannot be described by classic viscoelastic theories but rather by a loss of sphincter tone caused by reflex mechanism during anal distension. PMID- 1868970 TI - Neutrophil motility in Crohn's disease. AB - Neutrophil motility in normal subjects and Crohn's disease patients was assessed using both double and single filter assay systems with n formylmethionylleucylphenylalanine (FMLP) as the attractant, and in a single filter assay with Candida albicans in 10% serum as the attractant. Assays were performed in triplicate and included controls to eliminate the effect of random (non-stimulated) locomotion. After incubation at 37 degrees C, filters were fixed and stained and the numbers of neutrophils per filter field counted under the microscope. Stimulated migration was calculated by subtracting random from total migration. Compared to normal neutrophils, 56% more Crohn's disease neutrophils migrated towards FMLP in the double filter system (p = 0.01). With the single filter technique using FMLP as the attractant 58% more Crohn's disease neutrophils migrated (p = 0.002). With the single filter technique using C. albicans as the attractant 47% more Crohn's disease neutrophils migrated (p = 0.02). Neutrophil motility in patients with Crohn's disease is enhanced and results were not related to disease activity. PMID- 1868972 TI - Effect of hyperventilation on distal colonic motility and rectal sensitivity in irritable bowel syndrome. AB - Hyperventilation is associated with some symptoms suggestive of irritable bowel syndrome and has been implicated in provoking excessive oesophageal contractility. Sixteen patients with irritable bowel syndrome were therefore studied in order to assess the effect of hyperventilation on distal colonic motility and rectal sensitivity. No significant change in either the amplitude or frequency of colonic contractile activity was noted following hyperventilation, nor was any alteration in rectal sensitivity observed. This study shows that acute hyperventilation does not affect colonic motor activity or visceral sensitivity and suggests that hyperventilation and irritable bowel syndrome are not causally related. PMID- 1868973 TI - Effect of intravenous omeprazole on twenty-four-hour intragastric pH in patients with a history of peptic ulcer. Comparison of two four-dosage regimens. AB - To study the effect of intravenously given omeprazole on the 24-hour gastric secretion, 9 male patients with previously endoscopic proven duodenal ulcer disease were studied. Two four-dose regimens only differing in loading doses were compared. The study showed that 40 mg omeprazole, administered intravenously 4 times a day, is able to keep the gastric pH above 4 in 85% of the 24-hour study period and in 65% of the time pH was above 6. The corresponding values from the baseline period were 10 and 6%. There was no additional effect by a larger loading dose. PMID- 1868974 TI - Concordance of indirect methods for the detection of lactose malabsorption in diabetic and nondiabetic subjects. AB - In order to collect data on (1) the prevalence of lactose malabsorption and (2) the value of indirect diagnostic methods for hypolactasia in diabetics, we compared lactose tolerance tests using serum glucose, serum galactose (after oral ethanol intake) and breath hydrogen excretion as diagnostic cutoff in 144 nondiabetic and 46 diabetic subjects. A good rate of concordance was found for the hydrogen breath test and galactose-dependent lactose tolerance test. The glucose-dependent lactose tolerance test was found to be of satisfactory diagnostic value in nondiabetic subjects and was useless for diagnostic purposes in diabetics. Lactose malabsorption was no more frequent in diabetics than in controls and lactose intolerance was found to be less frequent in the diabetic group. A distinction between hypolactasia and other gastrointestinal disorders in diabetics is possible by ambulatory indirect tests. PMID- 1868976 TI - Scientific fraud and the Public Health Service Act: a critical analysis. PMID- 1868975 TI - CCK receptor antagonist loxiglumide alters uptake of CCK in perfused liver and pancreatic acini of the rat. AB - The aim of the present study was to analyze the effect of the specific cholecystokinin (CCK) receptor antagonist loxiglumide on hepatic and pancreatic processing of CCK-8 and the CCK analogue cerulein. Rat liver perfusion was performed in a non-recirculating system. CCK concentrations were measured by radioimmunoassay in perfusates from the inflow cannula (portal vein) and the outflow cannula (hepatic vein). In rat pancreatic acini, the effect of loxiglumide on internalization and surface-binding of radiolabelled CCK-8 was determined. Cerulein (20 nM, 2 nM) was extracted in a single pass through the liver by 29.7 and 25.4%, respectively. The hepatic uptake of CCK-8 (50 pM, 2 nM) was more than 90 and 89.9%, respectively. Loxiglumide drastically inhibited hepatic extraction of both peptides and reduced internalization of 125I-CCK-8 in pancreatic acini dose dependently by 39-93%. These results demonstrate that the potent CCK receptor antagonist loxiglumide significantly decreased CCK uptake by the liver and pancreas. PMID- 1868977 TI - Molecular manipulations of the multidrug transporter: a new role for transgenic mice. AB - Multidrug resistance in human cancer is associated with overexpression of the MDR1 gene which encodes a 170,000 molecular weight membrane glycoprotein that transports cytotoxic drugs out of cancer cells. The MDR1 gene is normally expressed in intestine, kidney, liver, and adrenal glands, and in tumors derived from these tissues, but it is not expressed in normal bone marrow. Transgenic mice that express the MDR1 gene in their bone marrow have been developed, and because of this expression these mice are resistant to the bone marrow suppressive effects of daunomycin, doxorubicin, taxol, and several other anticancer drugs. These mice can be used in several different ways to develop new types of drugs to treat human cancer.--Pastan, I.; Willingham, M. C.; Gottesman, M. Molecular manipulations of the multidrug transporter: a new role for transgenic mice. PMID- 1868978 TI - Inflammation in the course of early myocardial ischemia. AB - Experimental models of acute ischemic myocardial injury indicate that the inflammatory response after the ischemic event contributes to tissue damage. This is especially apparent with reperfusion of the ischemic tissue. In such models some therapeutic strategies designed to reduce neutrophil accumulation or function have resulted in apparently beneficial effects. Although such findings are encouraging, interventions into these pathological processes using specific molecular targets will require greater understanding of specific mechanisms. Current evidence indicates that potential sites of therapeutic intervention will be found in pathways leading to complement activation, generation of lipid derived mediators, adhesion of neutrophils to endothelial cells and cardiac myocytes, and activation of neutrophil secretory processes releasing, for example, proteolytic enzymes and reactive oxygen. Understanding the dynamic interplay between the mediators, adhesion pathways, and secretory processes that results in myocardial damage will allow a rational approach to controlling the detrimental inflammatory consequences of ischemia and reperfusion. PMID- 1868979 TI - Electron transfer in proteins: in search of preferential pathways. AB - Electron migration between and within proteins is one of the most prevalent forms of biological energy conversion processes. Electron transfer reactions take place between active centers such as transition metal ions or organic cofactors over considerable distances at fast rates and with remarkable specificity. The electron transfer is attained through weak electronic interaction between the active sites, so that considerable research efforts are centered on resolving the factors that control the rates of long-distance electron transfer reactions in proteins. These factors include (in addition to the distance and nature of the microenvironment separating the reactants) thermodynamic driving force and the configurational changes required upon reaction. Several of these aspects are addressed in this review, which is based primarily on recent work performed by the authors on model systems of blue copper-containing proteins. These proteins serve almost exclusively in electron transfer reactions, and as it turns out, their metal coordination sites are endowed with properties uniquely optimized for their function. PMID- 1868980 TI - Tolerance and suppressor mechanisms in experimental autoimmune encephalomyelitis: implications for immunotherapy of human autoimmune diseases. AB - Recent advances in understanding antigen recognition at the level of the trimolecular complex have provided new approaches for selective immunotherapy. Many of these approaches have been applied successfully to the animal model experimental autoimmune encephalomyelitis, and some are being tested in the human disease multiple sclerosis. In addition, new approaches utilizing nonspecific modulation of immune function are being explored in animals and humans. Immunospecific therapy in autoimmune diseases will ultimately be based on understanding how the normal immune system maintains unresponsiveness to self and how this state of self-tolerance is broken. Strategies for specific immune intervention in human diseases based on components of the trimolecular complex will have to take into account the polymorphism of the major histocompatibility complex in humans and the degree of heterogeneity among autoimmune T cells that react with an autoantigen. PMID- 1868981 TI - Soluble cytokine receptors: their role in immunoregulation. AB - A number of cytokine receptors exist in soluble form in the biological fluids of both animals and humans, a phenomenon that might have immunoregulatory implications in vivo. Although these soluble receptors specifically inhibit binding and activity of their respective cytokines in vitro, their actual function in vivo as cytokine inhibitors or as carrier proteins is unclear. Abnormalities in the production of these substances might contribute to the pathophysiology of immune and neoplastic diseases. Besides their role in regulating cytokine activity in vivo, soluble cytokine receptors hold significant potential for therapeutic use as very specific anticytokine agents and as indicators in diagnosis and assessment of immune parameters, prognosis, disease progression, response to treatment, etc., in a variety of autoimmune and malignant diseases. PMID- 1868982 TI - Pathologic concentrations of interleukin 6 inhibit T cell responses via induction of activation of TGF-beta. AB - Interleukin 6 levels are increased in a variety of clinical conditions including bacterial and viral infections, HIV infection, autoimmune diseases, certain neoplasias, and traumatic injury. In general, all these conditions are characterized by suppression of one or more manifestations of the immune response. Concentrations of IL 6 comparable to those found in the sera of immunosuppressed, thermally injured patients selectively inhibit T cell proliferative responses. This suppression is independent of IL 2-mediated responses, is dependent on macrophage activity, and is reversed by antisera specific for transforming growth factor-beta (TGF-beta). PMID- 1868983 TI - Depolarization decreases the [Ca2+]i sensitivity of myosin light-chain kinase in arterial smooth muscle: comparison of aequorin and fura 2 [Ca2+]i estimates. AB - Histamine stimulation of swine arterial smooth muscle is associated with a high [Ca2+]i sensitivity for increases in myosin light-chain phosphorylation. In contrast, KCl depolarization produces a relatively lower [Ca2+]i sensitivity (i.e., similar increases in [Ca2+]i induce less myosin phosphorylation). We evaluated whether 1) artifacts in the methodology for measuring [Ca2+]i or 2) true alterations in the [Ca2+]i sensitivity of myosin light-chain kinase were responsible for these apparent changes in the [Ca2+]i sensitivity of phosphorylation. The [Ca2+]i sensitivity of phosphorylation was higher with histamine stimulation regardless of whether the [Ca2+]i indicator was aequorin (which was loaded intracellularly by reversible hyperpermeabilization) or Fura 2 (which was loaded intracellularly by incubation of the tissues in Fura 2 AM). Aequorin and Fura 2 appeared to detect qualitatively similar stimulus-induced changes in [Ca2+]i with the exception that the initial response to histamine stimulation was different (histamine initially induced a large aequorin light transient and a relatively smaller increase in Fura 2 fluorescence). The [Ca2+]i sensitivity of myosin light-chain kinase extracted from KCl depolarized tissues was lower than the [Ca2+]i sensitivity of myosin light-chain kinase extracted from unstimulated or histamine stimulated tissues. These results suggest that depolarization specifically modifies myosin light-chain kinase to decrease its [Ca2+]i sensitivity. Changes in the [Ca2+]i sensitivity of myosin light-chain phosphorylation are not an artifact of the [Ca2+]i measurement technique. PMID- 1868984 TI - Mechanism of peroxide-induced cellular injury in cultured adult cardiac myocytes. AB - Reactive oxygen species contribute to the tissue injury seen after reperfusion of ischemic myocardium. We propose that toxicity originates from the effect that mitochondrial peroxide metabolism has on substrate entry into oxidative pathways. To support our contention, cultured adult rat cardiomyocytes were incubated with physiological concentrations of peroxide. The cellular extract and incubation medium were analyzed for adenine nucleotides and purines by reverse-phase high pressure liquid chromatography. Cellular glutathione efflux was determined by enzymatic analysis of the incubation medium. Pyruvate dehydrogenase (PDH) activity was determined in the cultured myocytes as well as in freshly isolated cardiac mitochondria using [1-C14]pyruvate. Extracellular glutathione rose 3.3 fold in response to small doses of peroxide (approximately 108 nmol/mg protein). Likewise, small quantities of peroxide reduced total cellular adenine nucleotides to 50-60% of control values with only a modest (0.95-0.91) reduction in energy charge [ATP + 1/2 ADP)/(ATP + ADP + AMP]. Peroxide-treated myocytes selectively release inosine and adenosine, as only these two purine degradation products were detected in the incubation medium. The most dramatic response was a peroxide dose dependent inhibition of PDH activity in cultured myocytes as well as freshly isolated mitochondria; just 65 and 30 nmol peroxide/mg protein induced a 50% reduction in cellular and mitochondrial PDH activity, respectively. In conclusion, physiological quantities of peroxide potently inhibit PDH in cultured cardiomyocytes and isolated cardiac mitochondria. PDH inhibition blocks the aerobic oxidation of glucose and inhibits the oxidative phosphorylation of ADP, which in turn leads to cellular adenine nucleotide degradation. PMID- 1868987 TI - The choline-deficient diet. PMID- 1868986 TI - Interpreting citations. PMID- 1868985 TI - A rational approach in the search for potent inhibitors against HIV proteinase. AB - Synthetic peptides described as dog renin inhibitors were found to effectively inhibit the aspartyl protease of human immunodeficiency virus (HIV). The selection of oligopeptides for the HIV protease inhibition study was based on 1) the current strategy of inhibiting aspartyl proteases with transition state analogs, and 2) our previous observations regarding optimal structural differentiation at the P2 position among human, dog, and rat renin inhibitors. In an in vitro assay system consisting of recombinant HIV protease and a synthetic decapeptide substrate (at pH 5.5), results show that HIV protease was unaffected by statine-containing analogs carrying histidine at the P2 position whereas analogs containing valine at the same position yielded anti-protease IC50 values ranging from 50 to 500 nM. As anticipated, some analogs were also shown to inhibit processing of recombinant polyprotein substrate by HIV protease in vitro. The anti-viral activity of three inhibitors was studied in HIV-infected CEM and MT-2 cells. Results showed that one compound, Ac-Naphthylalanyl-Pro-Phe-Val Statine-Leu-Phe-NH2 (antiprotease IC50 value = 0.4 microM), protected the infected cells effectively with IC50 values (0.73 microM for CEM cells and 0.88 microM for MT-2 cells). This antiviral effect is comparable to those obtained with AZT and ddC in parallel studies of MT-2 cells. PMID- 1868988 TI - [The aging of the heart: weight and structural changes in the left ventricle with age]. AB - Structural alterations of the cardiovascular system with aging are difficult to differentiate from superimposed pathologic processes. To determine whether aging "per se" affects the dimension of the heart, the weight of the heart, and the left ventricle and their rations to body weight, left ventricle wall thickness, the number of myocyte nuclei in the ventricle and the myocyte cell volume per nucleus were measured in 67 autopsies of subjects, 45 males and 22 females, who died from causes independent of cardiovascular diseases, from 17 to 90 years old. With aging, total heart weight increased slightly, while left ventricular and interventricular septum weights after dissection of the subepicardial fat decreased significantly (r = 0.44; p less than 0.001). Although left ventricular wall thickness remained constant with time, left ventricular weight to body weight ratio decreased progressively. At the structural level the number of myocyte nuclei within the left ventricle decreased (r = 0.45; p less than 0.001), whereas myocyte cell volume per nucleus increased (r = 0.30; p greater than 0.05) with age. Thus, the aging process of the heart is associated with a reduction in volume of the myocardial mass resulting from myocyte cell loss and reactive hypertrophy of the spared myocytes. PMID- 1868989 TI - [The mobile coronary unit of Florence: an evaluation of 10 years of prehospital cardiac care]. AB - In order to reduce the high mortality from ischemic heart disease, a mobile coronary care unit manned by a cardiologist has been operating in Florence since 1979. From 1980 to 1989 there were 13,029 interventions, 8,718 (66.9%) of which were cardiac emergencies. 1,718 (19.7%) patients showed acute myocardial infarction while in 2,274 angina was diagnosed (26.1%). Acute pulmonary edema and paroxysmal supraventricular tachyarrhythmias accounted, respectively, for 6.2% and 18.3% of total cardiac emergencies; moreover there were 753 (5.8%) attempted resuscitations in sudden cardiorespiratory arrest from cardiac causes. In acute myocardial infarction, the median time between the onset of symptoms and mobile coronary care unit arrival was 85 minutes, and 69.9% of patients were reached within 3 hours from the onset of symptoms. Ventricular fibrillation, ventricular tachycardia and asystole were observed respectively in 80 (4.6%), 42 (2.4%) and 50 (2.9%) patients. Success rate of emergency treatment was 81.3% for ventricular fibrillation, 88.1% for ventricular tachycardia and 18% for asystole. Prehospital mortality was 4.06%. The ECG picture of the 753 patients found in cardiac arrest showed sustained ventricular tachycardia in 12 (1.6%), ventricular fibrillation in 198 (26.3%), bradyarrhythmia in 28 (3.7%), and asystole in 431 (57.2%). Cardiopulmonary resuscitation was successfully performed in 230 patients (30.5%). Finally, more than 50% of the patients with angina, 20% of the patients with acute pulmonary edema, and 70% of the patients with paroxysmal supraventricular tachyarrhythmia were adequately treated at home and needed no hospitalization. The ten years experience of Florence Mobile Coronary Care Unit suggests that a community wide emergency cardiac care system can significantly reduce the pre hospital mortality and the time delays preceding thrombolysis and intensive care in acute myocardial infarction. Moreover, the cardiac "sudden death" can often be successfully treated. Most other cardiac emergencies may be adequately treated at home and unnecessary hospitalizations can be avoided. PMID- 1868990 TI - [Left ventricular filling studied by echo-Doppler in hypertensive and normotensive subjects]. AB - Purpose of the study was to evaluate the influence of different clinical and echocardiographic parameters on left ventricular diastolic filling in a group of 66 mild to moderate hypertensive subjects (mean age = 45.9 +/- 13.9 yrs) and in 49 normotensive controls (mean age = 44.2 +/- 15.9 yrs). All subjects underwent an echocardiographic study with pulsed Doppler evaluation of left ventricular filling. In the hypertensives, a noninvasive 24-hour blood pressure monitoring was performed. The ratio of early to atrial peak diastolic filling velocity (VmaxE/VmaxA) and the ratio between the respective velocity flow integral (Earea/Aarea) were significantly lower in the hypertensives compared to the normotensives (p less than 0.001). As within the hypertensives, office systolic blood pressure, average 24-hour mean blood pressure (24MBP), left atrial dimensions, and left ventricular mass index (MAXIND) were related both to age and diastolic filling. To study the relation between these parameters and diastolic filling a partial correlation test was used. The only variable related to diastolic filling, independently of age, was 24MBP (VmaxE/VmaxA vs 24MBP: r = 0.307, p less than 0.05, Earea/Aarea vs 24MBP: r = -0.261, p less than 0.05). Linear multivariate analysis using the method of stepwise regression established that age, 24MBP and heart rate were responsible for 75% of the VmaxE/VmaxA variance in the hypertensive group. To evaluate if the difference between the indexes of diastolic filling in the normotensives and the hypertensives varied according to age, we divided each group into two classes of subjects older and younger than 40 yrs. Under the age of 40 only VmaxE/VmaxA was significantly different in the two groups (p less than 0.05), while in the subjects older than 40 yrs both VmaxE/VmaxA and Earea/Aarea differed to a great level of statistical significance (p less than 0.001). The results of the present study allow the following conclusions: 1) age has the greatest influence on diastolic filling in both hypertensive and normotensive individuals. Diastolic filling is impaired in mild to moderate hypertension, when systolic function is still normal; 2) the worsening of diastolic filling determined by hypertension is more evident in the subjects greater than 40 yrs; 3) the only clinical variable that influences diastolic filling, independently of age, is 24MBP, while office blood pressure, MAXIND and left ventricular ejection fraction do not seem to be related to this clinical entity. PMID- 1868991 TI - [Standard contraction curves of the left ventricle for the objective quantification of segmental kinetics]. AB - Two left ventricle angiographically-standard contraction curves are proposed: one for the 30-degree right anterior oblique (RAO) projection, and the other for the 60-degree left anterior oblique (LAO) projection. These curves are obtained by a calculation which uses the end-diastolic and end-systolic silhouettes along with the longitudinal axes. The best calculation method, which is different in the two projections, has been identified by computer testing of a number of hypothesis over a "normal" population of 18 pairs of RAO and 7 pairs of LAO silhouettes. The working hypothesis was selected by minimizing the standard deviation. In both projections the percent reduction of 20 areas is performed. The 20 RAO areas are defined by 10 equidistant orthogonal coordinates which intersect the longitudinal axis; moreover, the longitudinal axis "angiographic shortening", becomes divided into "cavity real shortening" and "apical parietal effacement'. The 20 LAO areas are defined by radial axes spaced by 15 degree intervals. The proposed standard curves show a low standard deviation of the calculated points: mean 7.8% +/- 3.68 (SD) for the RAO curve, and mean 9.8% +/- 3.68 for the LAO curve. These curves achieve the goal of a standard reference for the objective evaluation of the left ventricle segmentary contraction analysis. PMID- 1868992 TI - [The bicuspid aortic valve: a "minor" congenital cardiopathy at risk of serious complications]. PMID- 1868993 TI - [The prevention of sudden death: lights and shadows]. PMID- 1868994 TI - [Informed consent: a utopia?]. PMID- 1868995 TI - [Late potentials: promises not kept or excessive expectations?]. PMID- 1868996 TI - [The classification of unstable angina]. PMID- 1868997 TI - [Unstable angina again]. PMID- 1868998 TI - [Three-dimensional ultrasonic diagnosis in gynecology and obstetrics]. AB - Three-dimensional reconstruction of an organ requires a coordinated sequence of cross-sectional scans. In ultrasound this can be solved by rotating the scan plane horizontally or vertically. Two scan heads have been built, one to rotate the plane around a horizontal, the second around a vertical axis. There are two ways to reconstruct the scans taken by ultrasound into a three-dimensional image: --to contour the surface of the organ in each scan and to reconstruct these contours to a ring-shaped structure. This procedure needs a lot of time; moreover, contouring must be performed via cursor on the screen. --calculate a transparent image of the organ. To obtain the best spatial image by the "transparent method", the image must be moved on the screen. Both methods of reconstruction are shown and compared in this paper. First experiences show that they can be applied in tumour diagnostic and in the diagnosis of malformations in early pregnancy. Further clinical studies will have to prove this. PMID- 1868999 TI - [Semiquantitative determination of the amniotic fluid volume in normal pregnancies]. AB - The amount of amniotic fluid was determined semiquantitatively in 600 pregnancies between the 12th and 41st week of gestation. Pregnancies at risk were excluded. The largest amniotic fluid area was measured sonographically in two dimensions. The mean plus/minus standard deviations are correlated with gestational age. A diagram has been prepared. Our results show good correlation with values from invasive quantitative examinations of amniotic fluid amount. However, our procedure is easy to perform and without hazard for the pregnancy, since it is non-invasive. PMID- 1869000 TI - [Effect of pregnancy and perinatal parameters--including mode of delivery--on survival rate of "low birth weight premature infants" (less than 1,500 g)]. AB - A retrospective analysis of 225 very low birth weight infants (less than 1500 g) was made, to assess the influence of the mode of delivery on the survival rate. In 186 preterm deliveries which could not be prevented by therapeutic measures, we included additionally certain gestational and perinatological parameters. Generally, an average survival rate of 72% was found in this study. In addition to the well-known negative influence of birth weight less than 1000 g and gestational age of less than 28 weeks, such parameters as antenatal pre pathological CTG findings, haemorrhages at the time of hospitalisation, and ineffectuousness of tocolytic drugs, were associated with a reduced survival rate. In contrast, the presence of anamnestic risk factors of preterm delivery and prolongation of gestation by one day and more improved the survival rate. Additional consideration of foetal presentation showed, that abdominal delivery was fundamentally safer in cases with breech and transverse presentation. Whether a higher survival rate can be achieved by vaginal delivery in cases of breech presentation with premature rupture of membranes or a gestational age greater or equal to 28 weeks, remains to be proved. A gestational age of less than 28 weeks or antenatal prepathological cardiotocographic findings will facilitate in future the decision to perform Cesarean section in cases of inevitable premature deliveries with cephalic presentation. PMID- 1869001 TI - [Intrauterine fetal death--analysis of incidence and causes in an unselected group of 199 twin pregnancies 1985-1989]. AB - Intrauterine death of one twin is an important factor, apart from prematurity in the high perinatal mortality rate in twin pregnancy. In 8 cases (4%) of a total of 199 twin pregnancies (2%), one foetus died antenatally. We examined retrospectively by single-case analysis the clinical and pathologico-anatomical features, which probably caused the intrauterine death of one twin. Placental insufficiency, associated with consecutive intrauterine growth retardation of either twin, was the leading reason in the relevant cases. In 23.3% of all twin pregnancies birth weight differences between both twins were 400 g and plus; in 5.1%, the differences were 700 g and plus. These data suggests, that in the monitoring or care of multiple pregnancies, intrauterine growth retardation of one foetus needs close observation as well as regular ultrasound examinations and cardiotocography. PMID- 1869002 TI - [Obstetric and ethical-legal problems in a twin pregnancy with anencephalus and polyhydramnios of the leading twin beyond the 28th week of pregnancy]. AB - Malformations are found twice as often in twins than in singletons. In the following case, we report on a twin pregnancy with anencephaly and polyhydramnion of the leading twin I, which was first diagnosed after 28 weeks of pregnancy. The foetal disease of twin I led to an appreciable dyspnoea of the mother that exacerbated to an incipient respiratory failure by the thirty-second week of pregnancy. The projected termination of pregnancy by Caesarean section based on a maternal indication was not performed, but instead a selective foetocide of the diseased twin. The live twin was delivered spontaneously without complications after thirty-eight weeks of pregnancy. The obstetric and legal ethical problems are discussed. PMID- 1869003 TI - [Comparison of perineal sonography and abdominal ultrasound examination in placenta praevia]. AB - This study describes a comparison between two different ultrasound methods used to localize a low-lying placenta or a placenta previa. The methods implemented were the abdominal ultrasound and the so-called "perineal scan", an ultrasound examination of the female urogenital tract, which is performed by using the perineum as an acoustic window. Between 1985 and 1988, 84 patients, suspected of having a low-lying placenta, were examined by perineal scanning. In all these cases it was possible to compare the results with those of abdominal ultrasound examinations documented in the patient's records. The "perineal scan" examinations were performed "blind", i.e., without knowledge of the results of prior abdominal ultrasound. Abdominal sonography was performed by a different examiner using the full-bladder-technique. Perineal scanning was done a short time after voiding. The results showed considerable and significant (p less than 0.001) discrepancies between the two methods; perineal scanning more often demonstrated higher grade diagnoses (27 patients, 32%) than vice versa (9 patients, 11%). These differences may be at least partially explained by the influence of bladder distension. Probably a full bladder produces false negative results more often than previously suspected. An analysis of pregnancy outcome yielded positive predictive values of 78% (abdominal ultrasound) and 86% (perineal scanning). Perineal scanning therefore seems to provide an uncomplicated and reliable means to verify an abdominal placenta localisation. PMID- 1869004 TI - [Pethidine or nalbuphine for obstetric analgesia?]. AB - Because of the risk of ventilatory depression, agonistic and partially agonistic/antagonistic opiates are well suited for providing pain relief in obstetrics. We compared two groups of 20 women each with pregnancy on term who received equipotent doses of nalbuphin (0.1 mg/kg) and pethidin (0.8 mg/kg) intramuscularly. We found a significantly longer (6h) and better analgesic effect in the nalbuphin group but also a significantly more pronounced sedation. Other side effects were fewer in this last-named group. There were no differences in the behaviour of the babies between both groups. We consider that because of the "ceiling effect" of ventilatory depression, nalbuphin may allow better analgesia without the risk of ventilatory depression of both mother and newborn. PMID- 1869005 TI - [Ferritin level in newborn infants after prepartal iron medication]. AB - Aim of the study was to find out the influence of iron medication of pregnant women on the iron levels of their newborn. In a prospective randomised study the iron-substituted group (n = 57) was treated with 2 x 1 Aktiferrin comp. Kps. (Merckle) during pregnancy, starting from the 22nd week. The control group (n = 46) had no medication during pregnancy. The substituted group had statistically significantly higher serum ferritin levels in the 30th week of pregnancy (p less than 0.048), higher levels measured in the cord blood at birth (p less than 0.001), and also the newborn of this group had statistically significant higher serum ferritin levels than the newborn of the control group (p less than 0.001). Our conclusion is that prepartal iron medication leads to increased iron stores in the newborn. PMID- 1869006 TI - [Cytogenetic analysis of sperm chromosomes in couples with habitual abortion]. AB - Genetic factors, especially numerical chromosome anomalies, play an important role in embryonic loss. Since somatic cell analysis cannot assess the risk of errors arising de novo during germ cell maturation, we investigated, whether the male gametes from couples with habitual abortion (group HA) carry a higher rate of anomalies, than those from donors without reproductive dysfunction (group K). Chromosomes were demonstrated after fusion of sperm with zona-free golden hamster ova. Our results indicate no significant difference between the two groups for the total rates of aneuploidy (HA: 3.6%, K: 2.0%) and structural anomalies (HA: 15.3%, K: 7.0%). However, the levels of chromosome breaks and acentric fragments were significantly higher in the abortion group (5.8% and 8.1%, respectively, vs. 2.4% each in group K). The implications of this fact remain to be investigated. PMID- 1869007 TI - [Melanoma of the vulva. Report of 12 cases]. AB - The present retrospective study includes 12 patients with melanoma of the vulva who underwent vulvectomy between 1977 and 1987. Six patients were less than 55 and 6 other patients more than 69 years old. Three women of the younger age group survived (31, 44 and 116 months, respectively), whereas three of them died of the tumour. In the patient group of over 69 years of age 4 patients died of the tumour, one patient did not appear for follow-up and one further patient died in the meantime. Nine patients suffered from deeply infiltrating tumours (Clark levels IV and V), 2 patients had a Clark level II tumour, and in one case the Clark level was unknown. Depth of infiltration correlated with the prognosis of disease, i.e. only one patient with deep tumour infiltration, but both patients with Clark level II tumours survived. Therefore, the importance of early diagnosis of melanoma of the vulva should be emphasized, and accurate inspection of the vulva should be indispensable in the course of routine gynaecological examination also in younger women. PMID- 1869008 TI - [Therapeutic results and toxic side effects of the cytostasan, adriamycin and vincristine combination as second line therapy in metastatic breast cancer]. AB - Remission rates of 30-50% can be obtained using different cytostatic combinations in second line therapy of metastatic breast cancer. The combination of adriamycin and vincristin with cytostasan revealed a remission rate of 50% in 62 CMF pretreated patients. Considerable toxic side effects led to a dose reduction of cytostasan and adriamycine in 43 patients without clinical efficacy loss. The long remission periods of the total responders (8-23 months) were remarkable. Both, 3 patients with bone +/- soft tissue metastasis and 4 patients with visceral metastasis benefited from a clinical total remission. The remission rates indicated no significant differences between the group of patients with soft tissue +/- bone metastasis (47.3%) and that with a predominantly visceral metastasis (50%). The CyAV-combination with a low dosage provides an effective therapeutical scheme with acceptable side effects for CMF-pretreated patients with breast cancer. PMID- 1869009 TI - [Effect of various factors on survival after recurrent and/or metastatic breast cancer]. AB - 145 women (22.2%) out of 652 patients with primary breast cancer, who were operated on between January 1980 and September 1988, developed tumour relapse until May 1990. The aim of our retrospective analysis in these 145 patients with local and/or distant tumour relapse was to evaluate the prognostic importance for further survival of the following factors: menopausal status, stage of disease, number of involved axillary lymph nodes, tumour grading, ER and PgR content, postoperative irradiation, adjuvant treatment, localisation of tumor relapse and relapse-free interval. Multivariate stepwise regression analysis of all these factors identified the number of positive axillary lymph nodes (0-3 versus 4+) with a relative risk (RR) of 2.49 and localisation of tumour relapse (local versus visceral metastasis RR = 2.08 and local versus bone metastases RR = 2.08) as the only two significant prognostic factors for further survival. Therefore, these two factors should be stratification criterias for prospectively randomized phase III studies in patients with tumour relapse after primary breast cancer. PMID- 1869010 TI - [Slit drainage versus Redon drainage in a clinical comparison--initial experiences with a new kind of wound drainage system]. AB - In a prospective, randomised study we compared the clinical properties of the established Redon drain with a new type of drain called "slit drain". Both types of drains were examined regarding the amount of drained fluid, the time elapsing until removal of the drain, the frequency of occlusion of the lumen as well as the patient's pain and the required force at extraction of the drain. The statistical analysis showed both drains to have equal abilities in draining of fluid if they were used under vacuum conditions. If used as nonsuction drains, the new device was able to drain more fluid than the established type of drain (p less than 0.05). Statistically relevant advantages of the slit drain were seen in a lower rate of obstruction of the lumen, a higher amount of drained fluid (as non-suction device) as well as an easier and less painful extraction. PMID- 1869011 TI - [Adjuvant chemotherapy in dysgerminoma]. AB - This is a report on a young patient with dysgerminoma of the right ovary. Right side adnexectomy and hysterectomy were performed initially. Due to the clearly elevated tumour marker levels, indicating an involvement of other germ cell elements, we opted for postoperative chemotherapy instead of radiotherapy. The follow-up included regular monitoring of the tumour markers. To date, there has been no indication towards tumour recurrence. PMID- 1869012 TI - [Vascular malformations of the uterus]. AB - Arteriovenous fistulae of the uterus are rare. We report on a patient with a vascular malformation of the uterus complicated by hypermenorrhea. Symptoms, possible complications and therapy are discussed. PMID- 1869013 TI - [Twin pregnancy in uterus didelphys]. AB - A case of twin pregnancy in uterus didelphys is reported. This rare event is discussed from obstetric aspects as well as that of dizygotic twins. PMID- 1869014 TI - [Sharing aseptic surgical units with the gynecologist?]. PMID- 1869015 TI - [Comment on the contribution by B. Warkentin: "On the question of the relation between psycho-physical acceleration and modern obstetrics"]. PMID- 1869016 TI - [Can midwifery be integrated into clinics?]. PMID- 1869017 TI - Reserpine non-selectively inhibits rat uterus contraction in vitro. AB - 1. Reserpine produced a direct in vitro non-selective inhibitory effect on smooth muscle contraction of endometrium-free rat uterus. 2. Reserpine uptake into uterine muscle and its antagonistic effect on contraction had a similar time course. 3. Reserpine had a relaxing effect similar to that of trifluoperazine and different from that of verapamil or papaverine, and also failed to exert any inhibitory effect on 45Ca uptake rate. 4. Both reserpine and trifluoperazine but not verapamil inhibited the acetylcholine-induced contraction when present during the Ca-release from intracellular stores. 5. It is hypothesized that reserpine exerts its inhibitory action intracellularly on the activation of smooth muscle contraction by sarcoplasmic Ca2+. PMID- 1869018 TI - Effects of NA0344, a new smooth muscle relaxant, on the actin-myosin-ATP interaction and myosin light chain phosphorylation in vitro. AB - 1. Effects of antibiotic NA0344, a smooth muscle relaxant, on phosphorylation of myosin light chain (MLC, 20 kDa) were compared with those on actin-myosin-ATP interaction using native actomyosin preparation containing MLC kinase activity. 2. MLC kinase was shown to be the site of action of NA0344. 3. NA0344 inhibited the interaction and phosphorylation with IC50 = 7.5 x 10(-6) and 1.6 x 10(-5) M, respectively. 4. The discrepancy between the inhibitory effects is explained that myosin is in an active form when myosin is fully phosphorylated. 5. However, the inhibitory effects of NA0359 and NA0362, analogs of NA0344, on the phosphorylation were similar to or more effective than those on the interaction, which cannot be explained by the active form hypothesis. 6. Plausible explanations for the discrepancies are discussed. PMID- 1869019 TI - The effect of prazosin pretreatment on hyperthermia produced by noradrenaline in rabbits. AB - 1. Hyperthermia produced by noradrenaline (NA) was accompanied by increased metabolic rate and vasoconstriction of ear skin vessels and a fall in evaporation heat loss. 2. Prazosin (PRA), administered as a single injection, decreased of hyperthermia elicited by NA mainly of attenuation the processes concerned with the heat production and increased of heat loss from respiratory tract and ear skin surface. 3. PRA administered in a 3 hr infusion did not only produce an abolishment of NA-induced hyperthermia but also exerted a hypothermizing effect. 4. PRA introduced intracerebroventricularly also induced a decline in core temperature, inhibiting the metabolic rate stimulated by this amine. 5. These results seem to suggest that NA-caused hyperthermia may be controlled through central adrenergic structures, which are effectively blocked by PRA. Besides, we have presented one more proof concerning the antihyperthermizing activity of PRA and its central point of activity catch. PMID- 1869020 TI - D-Ala-2-Me-Phe-4-Met-(O)-ol-enkephalin in the nucleus tractus solitarius of the rat produces cardiorespiratory depression. AB - 1. The synthetic Met-enkephalin, D-Ala-2-Me-Phe-4-Met-(O)-ol-enkephalin (FK 33 824). 1 or 2 micrograms, after its injection into the nucleus tractus solitarius (NTS) of Wistar rats, anesthetized with pentobarbital and breathing spontaneously, produced a transient increase in blood pressure followed by sustained and significant (P less than 0.05) hypotension and bradycardia. This occurred in a dose dependent manner. 2. FK 33-824 in the NTS, 1 or 2 micrograms, also produced a marked respiratory depression. 3. In anesthetized rats, in which hypoventilation was prevented by mechanical ventilation, there was a definite reduction in blood pressure and heart rate that was considerably and significantly (P less than 0.05) less than that observed in spontaneously breathing rats. 4. Blood pressure fluctuations occurred after NTS injection that were more marked in spontaneously breathing animals but still occurred in animals that were ventilated mechanically. 5. FK 33-824, 1 and 2 micrograms in the NTS was fatal within 100 min for all animals but was prevented by mechanical ventilation. Higher doses of FK 33-824, 10 micrograms in the NTS, however, induced fatal ventricular arrhythmias even in the mechanically ventilated rat. 6. Thus, FK 33-824 in the NTS decreases blood pressure and heat rate in spontaneously breathing as well as mechanically ventilated rats, but much of the effect on blood pressure and heart rate is due to the profound respiratory depression in the spontaneously breathing rat. PMID- 1869021 TI - Human erythrocyte as a model for investigating muscarinic agonists and antagonists. AB - 1. Human erythrocyte muscarinic receptor is further classified as M1 subtype by its binding of [3H]pirenzepine (a specific M1 antagonist). Conversely, binding of [3H]piperidinyl AF-DX116 (a specific M2 antagonist) is not detected. 2. There are high correlations between the binding efficacies of 25 known or putative cholinergic agents using either human erythrocyte membrane or mouse caudate homogenate. Also the in vitro data corresponds satisfactorily with in vivo data measuring the protective effect of these compounds against organophosphate poisoning. 3. The human erythrocyte membrane is an efficient model for investigating cholinergic agonists and antagonists. PMID- 1869022 TI - Estriol binding in uterine corpus cancer and in normal uterine tissues. AB - 1. The specific bindings of estriol (E3) and estradiol-17 beta (E2) to their specific receptors were investigated in endometrial carcinoma from 7 patients and normal tissues from their respective organs or from other patients. 2. In both cytosolic and KCl-extracted fractions from them, specific binding sites for E3 and E2 were detected, demonstrating the presence of their separate receptors in human uterus-associated tissues. 3. In certain cases (6 cases) of well differentiated adenocarcinoma, the ratio of concentration of E3 receptor to that of E2 receptor was almost equal to or higher than in other normal tissues. 4. These findings of unique localization of E3 receptor distribution may offer new insight into identification of endometrial carcinoma more likely to respond to hormonal influence or therapy. PMID- 1869023 TI - Pharmacological modulation of the antioxidant enzymes activities and the concentration of peroxidation products in fibroblasts stimulated with elastin peptides. AB - 1. Elastin peptides (kappa-elastin) prepared by alcoholic potassium hydroxide degradation of insoluble elastin were shown to increase the activities of antioxidant enzymes (SOD, CAT, GSH-Px) and the lipid peroxide concentration within fibroblasts. 2. The preincubation of cells with nifedipine (calcium channel antagonist) and trifluoperazine (calmodulin antagonist) caused the decrease in the activities of studied enzymes and the concentration of TBA reactive products in fibroblasts stimulated with kappa-elastin. 3. The preincubation with ketotifen (antiallergic drug) has no effect on the activities of SOD, CAT, GSH-Px and the lipid peroxide concentration in stimulated cells. 4. These data suggest the possibilities of pharmacological modulation of the biological effects induced by elastin-derived peptides. PMID- 1869024 TI - Rationale for frequency and dose of administration in gestrinone therapy for pelvic endometriosis in the experimental model of rabbit uterus. AB - 1. Gestrinone has been used for treatment of pelvic endometriosis, in doses of 2.5 mg twice a week. This study is designed to clarify it from the dynamics of sex steroid receptors in rabbit uterus. 2. Four different regimens were scheduled, namely daily 1 microgram estradiol-17 beta (E2, consistent with endogenous level of women) for 3 days, and together with either 30, 60 (consistent with 2.5 microgram of clinical dose) or 120 microgram(s) gestrinone, in single dose or with 20 microgram(s) gestrinone daily (divided dose in single 60 microgram(s) gestrinone administration) for 3 days. Receptors for estrogen (ER, type I and II) or progestin (PR) were determined by charcoal adsorption in cytosol and KCl extract, or sedimentation in non-KCl extractable fraction, using [3H]E2 or [3H]promegestone respectively. 3. Gestrinone decreased total ER (type I and II) levels, dose-dependently, except the case of 20 micrograms gestrinone daily in ER type II. Total ER type I level did not return to the pre-level until 3 days only after 120 microgram(s) gestrinone administration. Total ER type II level was decreasing in 3 days after 30, 60 or 120 micrograms gestrinone therapy. Total PR level was decreased in the order of strength: 120 micrograms gestrinone greater than 60 micrograms gestrinone greater than 30 microgram gestrinone greater than 20 micrograms gestrinone in group, and the recovery was not obtained until 72 hr only after 120 micrograms gestrinone therapy. The uterine weight was decreasing with the same strength in 3 days of the therapy independently upon the regimen. 4. In conclusion, gestrinone dose of 60 micrograms (2.5 mg of clinical dose) every 3 days is considered to be effective for anti-steroid action in sex steroid receptor dynamics in the rabbit uterus, contributing to the rationale for gestrinone treatment of pelvic endometriosis. PMID- 1869025 TI - Effect of alpha-glucosidase inhibition on the nonenzymatic glycation of glomerular basement membrane. AB - 1. The effect of the alpha-glucosidase inhibitor Acarbose on integrated glycemic control and on nonenzymatic glycation of glomerular basement membrane was examined in streptozotocin diabetic rats. 2. Treatment with Acarbose for 8 weeks after induction of diabetes significantly reduced the level of HbA1c and of glomerular basement membrane glycation. 3. Acarbose exerts a significant antihyperglycemic effect and has a salutary influence on the nephropathic process in experimental diabetes. PMID- 1869026 TI - The effect of Panax ginseng on the development of tolerance to the pharmacological actions of morphine in the rat. AB - 1. The effect of intraperitoneal administration of Panax ginseng on the development of tolerance to the analgesic and hyperthermic actions of morphine was determined in male Sprague-Dawley rats. Rats were rendered tolerant to morphine to different degrees by the subcutaneous implantation of either four pellets of morphine over a 3-day period or six pellets over a 7-day period. Each pellet contained 75 mg of morphine free base. Rats serving as controls were implanted with placebo pellets. 2. Daily administration of ginseng extract (6.25 50.0 mg/kg) for 3 days inhibited the development of tolerance to the analgesic effect but not to the hyperthermic effect of morphine in the four pellet schedule. 3. In six pellet schedule, daily administration of ginseng extract (25 and 50 mg/kg) for 7 days also inhibited the development of tolerance to the analgesic effect of morphine, but the 100 mg/kg dose had no effect. On the other hand, in six pellet schedule, the administration of ginseng extract (50 and 100 mg/kg) once daily for 7 days inhibited the development of tolerance to the hyperthermic effect of morphine. 4. It is concluded that in appropriate doses, ginseng extract has inhibitory activity on the development of tolerance to the pharmacological actions of morphine. PMID- 1869027 TI - Stimulatory effect of angiotensin II on electrolyte transport in canine tracheal epithelium. AB - 1. The present study examines the effect of angiotensin11 (A11) on Cl- and Na+ transport in canine tracheal epithelium. 2. A concentration-dependent increase in the potential difference and in short-circuit current of the trachea was found. 3. Frusemide reduced values of Cl- dependent electrical parameters; net Cl- flux from serosa to mucosa accounted for 72% of total short-circuit current. 4. Frusemide, indomethacin and chlorpromazine blocked the stimulatory effect of A11. 5. These reactions show that A11 stimulates ion transport across the canine tracheal epithelium and suggest that two mechanisms may be proposed to explain the action of A11 on Cl- flux: (1) Ca(2+)-dependent increase in intracellular cAMP and (2) increase in Na(+)-2Cl2-K+ Cotransport activity. PMID- 1869028 TI - A model to check the arrhythmogenic activity of antiarrhythmic drugs. AB - 1. In order to evaluate a condition which allows to check arrhythmogenic properties of antiarrhythmic drugs first experiences with the following model are presented. 2. Papillary muscles of guinea pig hearts were exposed to subthreshold concentration of aconitine (8 x 10(-8) M) for 30 min. 3. During the last 10 min of this period a lack of oxygen and glucose was additionally imposed on the muscle. 4. After this priming period, reoxygenation with glucose containing Tyrode solution was introduced and aconitine removed from the organ bath. 5. Restoring the normal conditions, the contractile force and the membrane potential completely recovered. Also the amplitude of the action pontial regained the control value. 6. Only the action potential duration displayed a prolongation of the late repolarization phase which can be described as a hump at a potential of about -55 mV. 7. 30 Minutes after the end of the priming period the muscles were exposed to antiarrhythmic drugs. 8. Quinidine, propafenone and gallopamil (at concentrations reducing the contractile force by 50%) induced a further prolongation of the action potential duration and provoked early after depolarizations thus acting arrhythmogenic. 9. In contrast, lidocaine and phenytoin did not prolong the action potential duration under this condition and were devoid of any arrhythmogenic activity. 10. The proposed model might offer a possibility to differentiate antiarrhythmic drugs with respect to their unwanted arrhythmogenic activity. PMID- 1869029 TI - Oxygen consumption stimulated by increases in permeability of Na+ of mouse diaphragm muscle in vitro. AB - 1. The effects on oxygen consumption of agents that modify Na(+)-permeability were examined in mouse diaphragm muscle perfused with a bathing solution that contained (+)-tubocurarine in a flow-through mode. Twitch tension and levels of Na+ and K+ in the muscle were also measured. 2. Unstimulated preparations decreased the concentration of oxygen in the bathing solution, indicating a basal level of oxygen consumption. Electrical stimulation of the muscle further decreased the concentration of oxygen. Potassium cyanide eliminated both the basal and the stimulated consumption of oxygen. 3. Veratridine facilitated the effect of stimulation at 0.1 Hz on both the consumption of oxygen and the twitch tension. Ouabain antagonized those effects. 4. Twitch contractions were blocked in the presence of dantrolene sodium or by pretreatment with ethylene glycol. Electrical stimulation of such preparations still caused a residual but considerably decreased consumption of oxygen. Ouabain and tetrodotoxin reduced the residual consumption of oxygen. 5. Ouabain significantly increased the levels of Na+ in the tissue, while veratridine alone did not. The effect of ouabain was further potentiated by the simultaneous presence of veratridine. 6. These results indicate that the enhancement of the sarcolemmal permeability to Na+ increases the rate oxygen consumption. This concept supports the hypothesis that Na+ homeostasis depends on energy consumption. PMID- 1869030 TI - Effect of sex steroids on cocaine lethality in male and female mice. AB - 1. Endogenous sex steroid levels were altered in mice via gonadectomy, via physiological or supraphysiological doses of testosterone and/or estradiol, and via tamoxifen dosing to antagonize estrogens. 2. The role of sex hormones in susceptibility to cocaine lethality was examined via the response of mice after endocrine alterations to an intraperitoneal (i.p.) cocaine HCl (75 mg/kg). Incidence of deaths was significantly decreased only in sham-operated males receiving estradiol or tamoxifen and in ovariectomized or sham-operated females receiving doses of estradiol. 3. The levels of estradiol in both sexes appeared to be more influential than were levels of testosterone as a determinant of susceptibility to cocaine. PMID- 1869031 TI - Recognition and reporting of child abuse: a survey of dentists. PMID- 1869032 TI - Odontogenic keratocyst involving impacted mandibular third molars. PMID- 1869033 TI - Application of glass ionomer cement to cervical root lesions with a vacuum-formed template. PMID- 1869034 TI - Patient exposure reduction in panoramic radiography. PMID- 1869035 TI - Trigeminal neuralgia. PMID- 1869036 TI - Evaluation of the Cariescreen SM method for enumeration of salivary mutans streptococci. PMID- 1869037 TI - The Canadian health care systems: lessons for American dentists. PMID- 1869038 TI - Heat-softened gutta-percha: an update. PMID- 1869039 TI - Transitional immediate complete dentures. PMID- 1869040 TI - Custom denture impression trays from existing dentures. PMID- 1869041 TI - Respiration and heat in contracting and non-contracting dissipative muscle. AB - The oxygen consumption-heat relationship is analyzed using a scheme of reactions underlying muscle aerobic metabolism. The enzymatic chemical reactions of the scheme are considered near equilibrium during a contraction, and far from equilibrium during energy dissipation in a non-contracting state. Implications show that for two different metabolic rates, the proportionality between oxygen consumption and heat is a very specific case, because of restricting necessary conditions. PMID- 1869042 TI - Effect of ultrasound on the functional state of nicotinic acetylcholine receptors in molluscan neurons. AB - The effect of ultrasound (2.64 MHz, 0.5 W/cm2) on acetylcholine-induced (ACh induced) current and surface distribution of ACh receptors (AChRs) were studied in neurons of the mollusc Helix pomatia. Upon switching on the ultrasound a negligibly small transient two-phase transmembrane current appeared; prolonged (5 25 min) action of beamed ultrasound waves significantly depressed the ACh-induced chloride current and caused the disappearance of functional nicotinic AChRs on parts of the neuronal soma distant from the axon. Pharmacological studies showed that the disappeared AChRs were responsible for changes in membrane permeability for chloride ions (AChRsCl). The results obtained in the present study indicate that ultrasound may be used as a selective inhibitor of AChRsCl in molluscan neurons. PMID- 1869043 TI - Mutual backbone phosphate group interactions promote DNA double helix bending at high salt concentrations in solution. AB - Results of free energy calculations connected with the backbone phosphate group interactions upon local bending and helical twist modifications of A-, B- or Z DNA at high salt concentrations have been reported recently (Jursa and Kypr 1990). Here we calculate energies necessary for DNA bending, using three models based on experimentally determined persistence length values. A comparison of energies following from the two quite different approaches suggests that high salt concentrations induce A- and mainly B-DNA bending into the double helix minor groove at least up to 10 degrees. PMID- 1869044 TI - A novel effect of vanadium ions: inhibition of succinyl-CoA synthetase. AB - Effect of vanadate and vanadyl ions on the ATP-dependent succinyl-CoA synthetase (A-SCS) solubilized by Lubrol-PX from the rat brain mitochondria was tested. Vanadate added to the assay medium at 10(-5) mol.l-1 and 10(-4) mol.l-1 concentrations inhibited the enzyme activity by about 50% and 94%, respectively. When the enzyme was solubilized from the mitochondria preincubated with 10(-4) mol.l-1 and 10(-3) mol.l-1 vanadate, the residual inhibitions were 55% and 100% respectively. The vanadyl cation also induced inhibition of the A-SCS activity but the effect was less expressed. At 10(-4) mol.l-1 concentration only 20% inhibition was achieved. The A-SCS solubilized from the mitochondrial subfractions (perikaryal, light and heavy synaptosomal) differed neither in the activity of A-SCS nor in the susceptibility toward action of vanadium ions. A strong dependence of the vanadate inhibition on the concentration of succinate was observed. The above effect (50% inhibition) could be demonstrated only at saturating concentration of succinate (50 mmol.l-1). The mechanism of vanadium ions action as well as differences between vanadate and vanadyl ions effects are discussed. PMID- 1869045 TI - 31P NMR study of postmortem metabolism in porcine and bovine muscles. AB - 31P NMR spectroscopy was used to evaluate interspecies differences in muscle fibre types and related postmortem metabolism. M. longissimus thoracis (MLT) and m. pectoralis superficialis (MPS) of bulls and MLT of pigs were investigated. In perchloric acid extracts NMR resonances for sugar phosphates (SP), inorganic phosphate (Pi), glycerophosphorylcholine (GPC), phosphocreatine (PCr), adenosine triposphate (ATP), adenosine diphosphate (ADP) as well as for NAD+/NADH could be distinguished. Also, glycogen and lactate contents and pH were determined. The relative contents of phosphorus compounds in bovine muscles of similar participation of muscle fibre are similar. Bovine muscles contain a relatively large proportion of PCr (48% of all phosphates 15 minutes post-mortem in MPS) whereas porcine MLT show lower PCr content (11% 15 minutes post-mortem). On the other hand, the ATP content is relatively higher in porcine MLT when compared with bovine muscles in the early phases of the postmortem processes. No NMR detectable levels of GPC were measured in porcine MLT in contrast to bovine muscles. This suggests that the GPC content does not depend solely on the fibre participation but is also animal species determined. The 24 hour postmortem metabolism patterns of bovine and porcine muscles have many common traits. CP disappeared first followed by ATP. Simultaneously, the Pi concentrations increased. However, the content of SP remained relatively constant in porcine, but not in bovine muscles where it increased only gradually. The significantly higher concentrations of SP and lactate as well as the lower values of glycogen and pH measured for porcine as compared with bovine muscles suggest an enhanced glycolysis during the early phases of postmortem processes in porcine muscles. PMID- 1869046 TI - T-lymphocyte development in scid mice is arrested shortly after the initiation of T-cell receptor delta gene recombination. AB - Scid mice lack functional lymphocytes because they carry a mutation that impairs rearrangement of immunoglobulin and T-cell receptor (TCR) genes. Rearrangement of TCR delta, but not gamma and beta genes, was routinely observed in DNA of scid thymocytes and thymocyte hybridomas. TCR delta gene rearrangements appeared to involve D delta 1, D delta 2, and J delta 1 elements only; rearrangement of elements upstream of D delta 1 (e.g., V delta 1) was not observed, and transcripts corresponding to fully assembled TCR delta genes (VDJ delta or VDDJ delta) were not detected in RNA from scid thymocytes. These findings suggest that D delta 1, D delta 2, and J delta 1 may be among the first TCR gene elements to undergo recombination and that scid T-lineage cells are developmentally arrested during or shortly after this stage of differentiation. One class of TCR delta recombination fragments (D delta 2-J delta 1) was amplified by the polymerase chain reaction (PCR) and cloned, and the recombination junctions were sequenced. Most fragments showed normal coding joints. Interestingly, five of seven coding joints that lacked N insertions showed evidence of recombination between short stretches (2-3 bp) of homologous sequence. As discussed, the general absence of V delta-, J gamma-, and J beta-associated rearrangements, despite the occurrence of normal D delta 2-J delta 1 rearrangements, raises the possibility that the scid mutation may cause premature cessation of TCR gene recombination and thereby arrest early T-cell development. PMID- 1869047 TI - Multiple trans-splicing events are required to produce a mature nad1 transcript in a plant mitochondrion. AB - The mitochondrial gene encoding NADH dehydrogenase subunit 1 (nad1) in Petunia hybrida is split into five exons, a, b, c, d, and e. With the use of a complete restriction map of the 443-kb Petunia mitochondrial genome, we have cloned these exons and mapped their location. Exon a is located 130 kb away from and in the opposite orientation from exons b and c. Exon d maps 95 kb away and in the opposite orientation from exons b and c. Exons d and e are separated by 190 kb. By performing the polymerase chain reaction on Petunia cDNAs, we have shown that transcripts from these five exons are joined via a series of cis- and trans splicing events to create a mature nad1 transcript. In addition, we have found 23 C----U RNA edit sites in Petunia nad1. RNA editing changes 19 of the amino acids predicted by the genomic sequence. PMID- 1869048 TI - Alternative splicing in the neural cell adhesion molecule pre-mRNA: regulation of exon 18 skipping depends on the 5'-splice site. AB - Two isoforms of the neural cell adhesion molecule (NCAM), termed NCAM-180 and NCAM-140, derive from a single gene via inclusion or exclusion of the penultimate exon 18 (E18). This alternative splicing event is tissue-specific and regulated during differentiation. To explore its structural basis, we have analyzed the pattern of spliced mRNA generated from transiently transfected minigenes construct containing this exon and portions of the adjacent introns and exons faithfully reproduces the differentiation state-dependent alternative splicing of the endogenous pre-mRNA. By systematic deletion and replacement analysis, we scanned the minigene for the presence of functionally important cis-elements. We identified two sequences that affected differentiation state-dependent regulation. One, the central part of E18, does not seem to contain a specific cis element essential for proper splice site choice, because extending the deletion restored correctly regulated expression of the splicing products. In contrast, the 5'-splice site is an important element for regulation. Replacing it with a corresponding sequence from the alpha-globin gene resulted in constitutive use of the optional exon. When placed in the alpha-globin gene it did not promote alternative splicing. Instead, we observed a strongly decreased efficiency of splicing of the downstream intron in undifferentiated cells. This block of splicing was partially relieved after differentiation. The results are consistent with a model in which skipping of E18 is controlled in part at the associated 5' splice site by trans-acting factors that undergo quantitative or qualitative changes during differentiation of N2a cells. PMID- 1869049 TI - Cooperativity at a distance promoted by the combined action of two replication initiator proteins and a DNA bending protein at the replication origin of pSC101. AB - We have investigated the interaction of the host-encoded DNA bending protein IHF, the host-encoded initiator DnaA, and the plasmid-encoded initiator RepA with the replication origin of pSC101. We have discovered that DNA bending induced by IHF in vitro promoted the interaction of DnaA protein with two physically separated binding sites called dnaAs and dnaAw. This cooperative interaction at a distance, most probably, caused looping out of the ihf site. We have also discovered that RepA protein binding to its cognate sites promoted enhanced binding of DnaA protein to the physically distant dnaAs site, probably also by DNA looping. The addition of RepA to a binding reaction containing IHF and DnaA further enhanced the binding of DnaA protein to the dnaAs site. Thus, the three DNA-binding proteins interacted with the origin, generating a higher order structure in vitro. On the basis of the results of the known requirement of all three proteins for replication initiation, we have proposed a model for the structure of a preinitiation complex at the replication origin. PMID- 1869050 TI - The cloned RNA polymerase II transcription factor IID selects RNA polymerase III to transcribe the human U6 gene in vitro. AB - Although the human U2 and U6 snRNA genes are transcribed by different RNA polymerases (i.e., RNA polymerases II and III, respectively), their promoters are very similar in structure. Both contain a proximal sequence element (PSE) and an octamer motif-containing enhancer, and these elements are interchangeable between the two promoters. The RNA polymerase III specificity of the U6 promoter is conferred by a single A/T-rich element located around position -25. Mutation of the A/T-rich region converts the U6 promoter into an RNA polymerase II promoter, whereas insertion of the A/T-rich region into the U2 promoter converts that promoter into an RNA polymerase III promoter. We show that this A/T-rich element can be replaced by a number of TATA boxes derived from mRNA promoters transcribed by RNA polymerase II with little effect on RNA polymerase III transcription. Furthermore, the cloned RNA polymerase II transcription factor TFIID both binds to the U6 A/T-rich region and directs accurate RNA polymerase III transcription in vitro. Mutations in the U6 A/T-rich region that convert the U6 promoter into an RNA polymerase II promoter also abolish TFIID binding. Together, these observations suggest that in the human snRNA promoters, unlike in mRNA promoters, binding of TFIID directs the assembly of RNA polymerase III transcription complexes, whereas the lack of TFIID binding results in the assembly of RNA polymerase II snRNA transcription complexes. PMID- 1869051 TI - The pituitary-specific regulatory gene GHF1 contains a minimal cell type-specific promoter centered around its TATA box. AB - GHF-1 is a pituitary-specific transcription factor responsible for activation of the growth hormone (GH) gene. The GHF1 gene is expressed exclusively in cells of the somatotrophic lineage, and its transcription is extinguished in somatic cell hybrids. The minimal sequences required for differential transcription of GHF1 in GH-expressing and -nonexpressing cell lines and somatic cell hybrids were localized to a 15-bp region surrounding and including its TATA box. This 15-bp fragment acts as a cell type-specific promoter element and is recognized by a transcription factor present in GH-expressing cell lines. Hence, in addition to enhancers and upstream promoter elements, the TATA element (TATA box plus surrounding sequences) can be, in certain cases, an important determinant of cell type-specific transcription. PMID- 1869052 TI - A new anatomical representation of the human visual pathways. AB - A three-dimensional, computer-aided reconstruction of the intracranial parts of the visual system, optic nerve, optic chiasm, optic tract, lateral geniculate body, optic radiation and striate area on the basis of anatomical serial cuts is presented in this paper. The computer-graphic representation simulates the illumination of a three-dimensional reconstruction. This study depicts for the first time a detailed anatomical reconstruction and illustrative representation of the striate area. An interactive investigation of the structure on the screen as well as a demonstration of the intracranial relationships between different neuroanatomical structures and comparisons with magnetic resonance, computed tomographic, and positron emission tomographic images is possible, providing that the neuroimaging uses the identical Cartesian coordinate system [22]. PMID- 1869054 TI - Evaluation of Keeler Pulsair non-contact tonometry: reliability and reproducibility. AB - Intraocular pressure was evaluated in 414 eyes using Keeler Pulsair tonometry in comparison with values obtained by Goldmann tonometry. No statistically significant differences were found between the two techniques. Landis K statistical analysis was used to evaluate the measurements obtained by two operators in 125 eyes, with the results indicating good reproducibility. In 20 eyes, a statistically significant difference was found between values obtained with patients in the seated vs supine positions, whereas measurements made with subjects' heads in a supported or unsupported position yielded no statistically different values. PMID- 1869053 TI - Primary orbital malignant lymphoma: a clinicopathology study of 17 cases. AB - We investigated the clinicopathologic characteristics of 17 patients (13 men and 4 women) with primary orbital malignant lymphoma using the Working Formulation. Most of the cases belonged to the low-grade malignancy group, and more women than men were in the histologically high-grade malignancy group. The phenotype of the tumor cells was investigated immunohistochemically. All cases showed the monoclonal feature of a B-cell lineage. All patients received chemotherapy with or without radiotherapy. Of 16 subjects, 15 achieved a complete remission; none of these patients has had a recurrence since the completion of the initial therapy (range of follow-up from 16 months to 10 years). One patient died. PMID- 1869055 TI - Threshold Amsler grid testing in diabetic retinopathy. AB - The Amsler grid is a suprathreshold target used to assess the central 10 degrees of the visual field; thus, it may fail to detect relative central scotomas. Low luminance conditions can be created by viewing the white grid on a black background through two cross-polarizing filters that vary light transmission and change the procedure to a threshold Amsler grid (TAG) test, thereby increasing its sensitivity. A total of 26 patients with diabetic retinopathy were tested by standard Amsler grid, TAG, and tangent screen. Four scotomas were detected by Amsler grid testing; each of these scotomas expanded in size on retesting with the TAG. TAG testing revealed 22 scotomas more than five times the number seen with conventional Amsler grid testing; tangent-screen examination confirmed 9 of these defects. In many cases, fundus photography and fluorescein angiography revealed pathology that correlated with the scotomas detected only by TAG testing. It thus appears that the TAG test is a rapid, high-yield, and sensitive means of assessing the central visual field in patients with diabetic retinopathy. PMID- 1869056 TI - The effects of weighting the "mean defect" visual field index according to threshold variability in the central and midperipheral visual field. AB - Two visual field indices, the mean defect (MD) of Flammer and the mean deviation (MD) of Heijl, have found wide acceptance among perimetrists. We compared these indices in 169 visual fields from normal- and high-tension glaucomatous eyes. Visual field damage in these eyes varied from slight to severe. In computations of the mean deviation index, the threshold values are weighted by the threshold deviations obtained from normal eyes as a function of eccentricity. However, the present study shows that the differences between the two indices in the population studied are negligible. Thus, subsequent interpretation is not affected by the choice of index, and the two MD indices may be considered to be interchangeable for the types of visual fields used in this study and for program G1 examinations carried out using Octopus automated perimeters. Since we found smaller increases in local intersubjective fluctuations as a function of eccentricity in 274 normal visual fields as compared with results published by others, caution is indicated for interpretation of the visual field using probability weighting. PMID- 1869057 TI - Tuberculin skin-test-induced uveitis in the absence of tuberculosis. AB - A 16-year-old Caucasian girl who showed no evidence of tuberculosis or other systemic disease developed acute panuveitis progressing to bilateral serous retinal detachments following purified protein derivative (PPD) skin testing on two separate occasions separated by an interval of 8 years. Both episodes responded rapidly to steroid therapy. Uveal hypersensitivity to PPD skin testing has been described in the presence of ocular or systemic tuberculosis, Eales' disease, and the Vogt-Koyanagi-Harada syndrome (VKH). Our case, however, suggests that profound uveitis may be precipitated by routine PPD skin testing alone. PMID- 1869058 TI - Analysis of electro-oculographic artifact during vertical saccadic eye movements. AB - The analysis of vertical saccades by electrooculography (EOG) is limited by the presence of waveform artifacts that occur with both upward and downward saccades. The artifacts have been shown to increase the calculated velocities of upward saccades. For better evaluation of the nature of these artifacts, voluntary vertical saccades were recorded by EOG and magnetic search coil in five normal subjects and by EOG only in two patients who had previously undergone enucleation. All subjects demonstrated peaked EOG artifacts during vertical saccades. The amplitude of these artifacts was decreased but not completely eliminated by eyelid or eyeball fixation during the attempted saccade. Peak saccadic velocities were also decreased by eyelid fixation, but EOG measurements were generally less accurate than those obtained by search coil. There is evidence that these artifacts may be the result of a combination of eyelid electrical activity and resistance effects. PMID- 1869059 TI - Long-term follow-up of diabetic retinopathy for up to 71 months after combined renal and pancreatic transplantation. AB - This study reports the course of diabetic retinopathy in 25 patients (41 eyes, 9 one-eyed patients) who had undergone successful renal and pancreatic transplantation. The mean duration of follow-up was 38 months (range, 15-71 months). Visual acuity improved in 13 eyes (32%), remained stable in 19 (46%) and deteriorated in 9 (22%); only 2 of the latter 9 eyes (5%) sustained severe visual loss according to the definition of the Diabetic Retinopathy Study Group. The frequency and severity of vitreous hemorrhage improved in 19 eyes (46%), remained unchanged in 18 (44%) and worsened in 4 (10%). In comparison with other modes of treatment such as intensified conventional insulin therapy and artificial insulin delivery systems, the combined renal and pancreatic transplantation seems to have advantages concerning the course of proliferative diabetic retinopathy. PMID- 1869060 TI - Light-sense, flicker and resolution perimetry in glaucoma: a comparative study. AB - A total of 106 eyes of 106 patients with different types of glaucoma were examined by automated light-sense, flicker and resolution perimetry (Humphrey Field Analyzer, program 30-2; flicker perimeter as described by Lachenmayr [16, 18]; resolution perimeter as devised by Frisen [4, 6, 8-11]). The fields were classified in a masked fashion as being normal or as having purely diffuse loss, purely localized loss or diffuse as well as localized loss. As compared with light-sense perimetry, resolution perimetry had a markedly lower sensitivity in the detection of glaucomatous damage (77%) but a high specificity (93%); the comparison of resolution perimetry with flicker perimetry showed similar results (sensitivity, 75%; specificity, 85%). When flicker perimetry was compared with light-sense perimetry and vice versa, the sensitivity was high (95% and 94%, respectively), but the specificity was low (57% and 62%, respectively). The prevalence of detection of diffuse loss by both light-sense and resolution perimetry was related to visual acuity, whereas flicker perimetry did not show such a relationship. PMID- 1869061 TI - Intraocular pressure response to the replacement of pilocarpine or carbachol with echothiophate. AB - In 20 patients with open-angle glaucoma in aphakia or pseudophakia whose intraocular pressure had remained uncontrolled on their current medical therapy, the medication was changed from pilocarpine or carbachol to echothiophate iodide. In all, 12 patients (60%) showed a statistically significant improvement in pressure control, 7 (35%) showed no change, and 1 had higher pressure. One-third of the patients with improved intraocular-pressure control eventually required laser or incisional surgery after a mean of 23 months, whereas the remaining subjects were controlled for the duration of the follow-up, which averaged 26 months. Side effects encountered during echothiophate iodide treatment included ocular irritation, decreased vision, and one retinal detachment. PMID- 1869062 TI - Endothelial barrier function after phacoemulsification: a comparison between diabetic and non-diabetic patients. AB - In all, 21 diabetic and 23 non-diabetic patients underwent endothelial fluorophotometry before and at 4 days, 3 weeks and 6 weeks after phacoemulsification with posterior chamber intraocular lens (IOL: PMMA) implantation. After topical fluorescein instillation, fluorophotometry was performed using an automated computerized fluorophotometer. The aim of this study was to assess early postoperative endothelial damage quantitatively and to detect possible differences between diabetic and non-diabetic patients in that regard. Preoperatively, the endothelial permeability of diabetic patients did not differ from that of non-diabetic individuals (P = 0.5). At 4 days after phacoemulsification with posterior chamber IOL implantation, endothelial permeability was significantly increased in both groups (P less than 0.001), but significantly more so in diabetic patients (P less than 0.001). The endothelial barrier function had fully recovered 3 weeks after surgery in non-diabetic subjects and 6 weeks after surgery in diabetic patients as well. PMID- 1869063 TI - A 3-month comparison of 1% and 2% carteolol and 0.5% timolol in open-angle glaucoma. AB - Carteolol, a nonselective beta-adrenergic antagonist with intrinsic sympathomimetic activity, was compared in 1% and 2% topical solutions with 0.5% timolol in 105 patients with primary open-angle glaucoma. In this double-masked, randomized 3-month trial, all three preparations significantly lowered intraocular pressure throughout the study, with no significant differences being observed. There were also no significant differences among the three preparations with regard to ocular or systemic adverse reactions, including heart rate and blood pressure. PMID- 1869064 TI - Spatial-frequency-dependent changes in the human pattern electroretinogram after acute acetyl-L-carnitine administration. AB - Acetyl-L-carnitine (LAC) is a neuroactive compound that is thought to be involved in cholinergic transmission. The effects of acute intravenous LAC administration (30 mg/kg) on pattern-evoked electroretinograms (P-ERGs) were evaluated in nine healthy volunteers ranging in age between 21 and 27 years. Nine age-matched, normal subjects treated with a placebo served as controls. Steady-state (8 Hz) P ERGs recorded in response to counterphased sinusoidal gratings of variable spatial frequency (0.6-4.8 cycles/degree) were obtained before and at 20, 50 and 80 min after LAC or placebo administration. The amplitude and phase of the Fourier-analysed P-ERG second harmonic were measured. As compared with placebo treated controls, LAC-treated subjects showed a selective P-ERG amplitude increase (Mann-Whitney rank test: P less than 0.05), which was found 80 min posttreatment at a spatial frequency of 4.8 cycles/degree. For the same stimulus a significant (P less than 0.05) P-ERG phase shortening (at 50 min after drug administration) was also found. The spatial frequencies of other stimuli did not show a significant difference between the LAC- and placebo-treated groups. These results indicate that acute LAC administration induces a spatial-frequency dependent enhancement of the human P-ERG. This is compatible with a cholinergic excitatory effect and suggests a therapeutic role for this compound in retinal dysfunctions with selective vulnerability to medium-high spatial frequencies. PMID- 1869065 TI - Diffuse and localized glaucomatous field loss in light-sense, flicker and resolution perimetry. AB - A total of 75 eyes in 75 patients with different types of glaucoma (21 eyes with low-tension glaucoma, 49 with primary open-angle glaucoma and 5 with pigmentary glaucoma) were examined by automated light-sense, flicker and resolution perimetry. All fields were classified in a masked fashion as being "normal" (N) or as having "diffuse loss" (D), "localized loss" (L) or "diffuse plus localized loss" (DL). The frequency distributions for the various field loss categories were plotted against the highest intraocular pressure ever reported in the patients' records. The frequency distribution for the purely localized defects showed a peak at 20 mmHg and were markedly skewed to low pressure values, whereas those for both diffuse plus localized damage and purely diffuse loss peaked at about 30 mmHg. The data suggest that diffuse field loss may be an indicator of pressure-induced damage. PMID- 1869066 TI - The effect of trabeculectomy on the aqueous humor flow of the unoperated fellow eye. AB - Computerized anterior-chamber fluorophotometry was used to investigate the effect of unilateral antiglaucomatous trabeculectomy on the dynamics of aqueous humor in the unoperated fellow eye. In 14 patients with bilateral primary open-angle glaucoma, pigmentary glaucoma or exfoliation glaucoma, antiglaucomatous trabeculectomy was performed in one eye in which medical management of glaucoma had failed. The fellow eye in all patients had a well-defined history of glaucoma and had been treated with different sorts of medication. The medical management of the unoperated fellow eyes was continued throughout the study. Aqueous humor flow was measured in these eyes prior to surgery and on the 5th day after trabeculectomy. Systemic medication was discontinued from 48 h prior to surgery until second fluorophotometry. The average postoperative flow in the fellow eyes increased from 2.56 to 2.92 microliters/min (P less than 0.05%, paired t-test). The increase in flow in the fellow eyes was independent of topical antiglaucoma medication and of the diurnal rhythm of aqueous humor dynamics. The results of the study indicate that filtration surgery in one eye triggers a CNS-mediated, reflective increase in aqueous flow to maintain physiological stability in the anterior chamber of the surgically treated eye. Since this CNS reflex on aqueous humor dynamics affects both eyes, the clinical observation of intraocular pressure (IOP) dysregulation in the unoperated fellow eye following unilateral trabeculectomy is now understandable. PMID- 1869067 TI - Glaucoma and Peters' anomaly. A clinicopathologic case report. AB - A 26-year-old black woman with Peters' anomaly who had been followed since early childhood developed an open-angle form of glaucoma, which required filtering surgery. Light and electron microscope studies of the trabeculectomy specimen, which was obtained by en bloc resection of the trabecular meshwork and iridectomy specimen, revealed that the structures of the anterior-chamber angle were grossly normal aside from evidence of premature aging on the basis of abundant broad banded collagen fibers in the trabecular lamellae. PMID- 1869068 TI - Inhibitory effects of ovomacroglobulin on bacterial keratitis in rabbits. AB - We studied the inhibitory effects of chicken egg-white ovomacroglobulin (ovoM) on keratitis induced by 56,000-Da protease (56 KP) of Serratia marcescens and by elastase (PE) and alkaline protease (PAP) of Pseudomonas aeruginosa. The effects of ovoM on the serratial and pseudomonal keratitis in rabbits were also elucidated. In one model, four drops of 56 KP, PE, or PAP (1 mg/ml) were applied to wounded corneas of eight eyes. Thereafter, 80 microliters ovoM (10 mg/ml) was dropped into four eyes and 0.01 M phosphate-buffed 0.15 M saline (pH 7.4) into the other eyes as a control. The other in vivo test system involved intrastromal injection of S. marcescens or P. aeruginosa, by which each sample (10(5)-10(7) colony-forming units) mixed with ovoM was injected into one cornea and the other cornea received organisms without ovoM. OvoM completely inhibited the activity of these bacterial proteases in vitro and reduced corneal destruction in experimental keratitis in rabbits. In addition, greatly accelerated wound healing was observed. PMID- 1869069 TI - Responses to oxygen deprivation: variations among human corneas. AB - The cornea's interface with the atmosphere makes it uniquely accessible among avascular tissue for the study of local oxygen demand and proximal reservoir dynamics. Corneal oxygen-uptake rates obtained under normoxic vs hypoxic conditions are not predictive of each other. Proximal tissue reservoirs appear to play a role in moderating oxygen demands following periods of hypoxic stress: as the ratio of epithelia/stromal thickness rises, so does oxygen demand (r = +0.932, P = 0.01). The thickness of the stroma was most closely related to the oxygen uptake rates associated with the normal, open eye (r = +0.773, P = 0.07), whereas the thickness of the epithelium was more closely related to rates obtained after the cornea had been deprived of oxygen (r = +0.783, P = 0.07). PMID- 1869070 TI - The increasing sclerosis of the human lens with age and its relevance to accommodation and presbyopia. AB - By means of a fine conical probe and a miniature dynamometer, the resistance to penetration of different lens layers was measured. In clear human lenses the power of resistance of the lens nucleus increases with age, mostly due to the "hardening" of the nucleus. A distinct hardening of the nucleus as opposed to the cortex has been found to occur in lenses as young as 20 years of age. This "firmness" of the lens nucleus, occurring between the ages of 20 and 60 years, coincides with the decrease in accommodation range and the onset of presbyopia. PMID- 1869071 TI - Ultrastructure of persistent hyperplastic primary vitreous (PHPV) PMID- 1869072 TI - Vasoconstrictive effect of topical timolol on human retinal arteries. PMID- 1869073 TI - [Industrialization of the modern world and its impact on health]. PMID- 1869074 TI - [Vibration-acoustic characteristics of pneumatic portable perforators and prognosis of vibration pathology in mine workers in the Far North]. PMID- 1869075 TI - [Screening-diagnosis of occupational hearing disorders]. AB - Hypoacusis is of leading prevalence in the structure of occupational morbidity in the USSR. Preventive medical examinations are considered a major prophylaxis measure which can be further improved with automatized screening diagnostic systems. Supplementary devices to the "ASKORS" automatized system are proposed to diagnose the pronosological forms of noise-induced health disorders. PMID- 1869076 TI - [Comparative analysis of oncological morbidity in the population of an industrial city and workers of a metallurgical plant]. AB - Analytical epidemiology techniques were used to study the malignant neoplasms prevalence in the population of Magnitogorsk (400,000), and among the workers engaged in the Magnitogorsk metallurgical plant (64,000 workers). Revealed was that the malignant neoplasms related morbidity rate was 1.6 higher in men and 3.2 higher in women among the plant workers as compared with the city population in general. The cancer risk factors were predominantly occupational ones, e. i. the major industrial carcinogens--benzopyrene in tars and carbon-black; benzol, chromium and nickel in the dust; the carcinogenesis modifying substances- nitrogen oxide, sulfur dioxide, phenols, iron oxides, lead and its non-organic compounds, high temperatures. The data received can be used in further studies and elaboration of primary preventive measures. PMID- 1869077 TI - [Hygienic assessment of manual labor during vegetable growing in hot houses]. AB - The article provides an assessment of the physical load labour conditions among hot-house female workers in major agrotechnical operations. The study was based on the evaluation of physical power inputs by means of indirect calorimetry. The average physical power inputs indices were evaluated at 280 kcal/hour. The labour conditions were ascribed to Group 3, which necessitated mechanization of major agrotechnical operations and optimal labour and leisure regimen. PMID- 1869078 TI - [Assessment of the functional status of the engineering-technical staff at a machine-building plant]. AB - For early detection of functional disorders and risk-factors among the engineering staff at a machine-building plant, a set of highly informative, physiologically grounded and accessible techniques were used. To improve the patterns of out-patient screening of the staff, the contributors used physiologic and psychologic testing techniques, ECG monitoring registration in dynamics in the real occupational conditions, and riskometry, which facilitated the substantiation procedures for individual medical recommendations. PMID- 1869079 TI - [Substantiation and assessment of the effectiveness of hygienic recommendations for healthier work conditions of operators at seismic-acoustic stations]. AB - The labour conditions of seismic operators were studied as a sample of similar professions engaged in acoustic control services. Depending on the number of the sectors under control and the seismic activity in the area, the enthropy of the sounds controlled and the information volume were assessed within 2.2-2.62 and 1.29-1.81 bit/symbol, respectively. The physiological functions' analysis in dynamics for a shift and a week revealed the peculiar features of overstrain characteristic of the working hours in a shift, particularly towards the 3rd and 6th day of the week. The recommendations proposed were designed to reduce overstrain and improve the operators' functional state at work. PMID- 1869080 TI - [Significance of morphofunctional assessment of tissue basophil reactions in prognostication of harmful effects of chemical substances]. AB - The article contains a comparative analysis of experimental data on the assessment of the general toxicological, gonadotrophic effects and morphofunctional reactions of tissue basophils under the influence of 4-bromine-o xylene, carbon disulfide and pyracryl. Established was the gonadotrophic action of pyracryl against the growing activity of tissue basophils manifested through increased infiltration and high-level degranulation in female rats' reproductive organs. Demonstrated was that, under the influence of low-intensity chemical factors, tissue basophils morphofunctional reactions were those of organ-related nature. The quantitative assessment of tissue basophils was proposed as an informative model for studies of selective (gonadotrophic) actions of low intensity chemical substances. PMID- 1869081 TI - [Prognostication of physical work capacity under the effect of carbon monoxide and raised air temperature and decreased oxygen contents]. AB - Experimental studies performed on volunteers resulted in formulating an equation which characterized degrees of physical working capacity decrease depending on the carbon monoxide concentration levels and duration of its influence at high temperature levels (+50 degrees C) of the air and lowered barometric pressure (560 mm). A nomogram was charted to forecast degrees of physical working capacity decrease in man at the carbon monoxide concentration levels from 500 to 2000 mg/m3 at time intervals ranging from 0 to 30 min. PMID- 1869082 TI - [Integral-probability assessment of development of occupational diseases using Bayes' formula in building-land improvement and car repair industry]. AB - Integral probability technique used for the assessment of occupational diseases facilitated the evaluation of variability in the parameters of unfavorable industrial factors, as well as their complex action, the occupational pathologic developments "probability and risk groups identification. The technique proved valuable in charting the priority list of hygienic and health improvement measures to prevent the hazardous factors" influence depending on their probability indices. PMID- 1869083 TI - [Substantiation of maximum permissible concentration of nutrient yeasts obtained during utilization of waste products in cellulose-paper industry]. AB - The contributors used the sensibilization threshold to establish MACs for the dust of the fodder yeast produced as a result of pulp and paper waste products' recycling. The product belongs to the group of substances with low toxicity. It does not produce local irritation and exhibits sensibilization properties in case of both epi- and intracutaneous introduction. The sensibilization threshold in repeated introductions of protein-containing dusts was registered at 4.1 mg/m3. In industrial conditions, the fodder yeast concentrations at the level of about 4 mg/m3 caused increased morbidity with temporary disability. PMID- 1869084 TI - [Approaches to development of diagnostic allergens for observation of workers engaged in the production of microbial fodder biomass and population of development zones and regions of microbiological plants (review)]. PMID- 1869085 TI - [Syndrome of "unhealthy" accommodations as a hygienic problem (review of foreign literature)]. AB - The article provides an analysis of medical literature data referred to the epidemiology and hygienic value of 'the syndrome of unhealthy shelter' (SUS). Issues related to architectural and design properties, various industrial and non industrial factors, personal characteristics of the staff in relation to the SUS genesis are discussed in detail, as well as the SUS general and specific symptoms' dependence on the intensity of all these factors. Methodologies for hygienic analysis of SUS are also proposed. PMID- 1869086 TI - [Psychological characteristics of the personality of the sanitary service physician and his job satisfaction]. AB - The contributors propose the results of a psychological study in the personal peculiarities of sanitary service physicians depending on their qualification and duration of work. The study was based on testing 65 persons attending postgraduate courses on occupational, communal and radiation hygiene. Particular attention was focused on the communicative skills of high qualified physicians. The proposed technique provides valuable information which would facilitate physicians' professional skills, and provide guidance in teaching them. The technique can also be used in charting systems of professional incentives for this group of medical staff. PMID- 1869087 TI - [Effects of fiber bronchoscopy on partial pressure of oxygen in the skin of miners with diseases of respiratory organs]. AB - Influence of fiber bronchoscopy (FBS) on the partial tension of oxygen (pO2) in the skin was studied in 17 respiratory disorders affected miners, with no stable FBS-caused gas exchange disorders established. The patients affected with atrophic endobronchitis actually did not exhibit pO2 changes in response to FBS. In the catarrhal and hypertrophic endobronchitis cases, FBS-related pO2 content decrease was registered with subsequent increase to the initial level 24 hours later, which was explained by bronchial permeability improvements after the FBS procedures. PMID- 1869088 TI - [Occupational morbidity of miners engaged in the capital building of iron ore mines]. AB - The article contains data on the 1961-1985 occupational morbidity rates in the workers engaged in the Krivbass iron-ore mines, and narrates on the morbidity rates, structure and dynamics for different professions, age-groups and duration of work. An analysis is given of the concomitant somatic diseases, along with proposals for investigating ways and means of improving technologies in non blasting iron-ore mines. PMID- 1869089 TI - [Morbidity and prevention of allergic diseases in a tire plant]. PMID- 1869090 TI - [Labor hygiene and health status of operators engaged in irrigation using stock sewage]. PMID- 1869091 TI - [Triadimefon metabolism in the body of white rats]. PMID- 1869092 TI - [Assessment of probability of vibration disease caused by local vibration taking into consideration concomitant factors]. AB - The article sets forth a theoretical basis for the evaluation of the probability of vibration disease caused by local vibration, with due account of the concomitant factors and with recommendations with regard to the assessment of the aggravating and normalizing factors. Basing on the original data and medical literature information, the contributors provided formulae and charts for the assessment of vibration disease, risks caused by noise, cold microclimate, physical overload, and cigarette smoking as an individual factor. A concept was proposed with regard to the risk-free dosage. The concept was viewed as a new hygienic and occupational category, which facilitated evaluating the real occupational risk levels for any profession and their consequent minimizing. PMID- 1869093 TI - The accuracy of frozen section diagnosis of ovarian tumors. AB - We compared all frozen section examinations of ovarian tumors during a 6-year period in our institute with the final diagnosis from paraffin sections. In this period, 946 ovarian tumor specimens were removed for histologic assessment; 176 (18.6%) had frozen section examination. Final histological diagnosis was divided into benign (55.1%), borderline malignant (10.3%), and malignant (34.6%). Sensitivity of the frozen section method for malignant or borderline disease was 83.5% and specificity for a benign lesion, 92.8%. Predictive values and 95% confidence intervals were computed: 100% (93-100%) for malignancy, 62% (32-86%) for borderline malignancy, and 92% (85-96%) for a benign disease. Diagnostic problems occurred in large borderline tumors of mucinous cell type. Analysis of the 12 false negative diagnoses revealed that a sampling error was involved in 11 cases. A judgment error was made in the only false positive and in 1 out of 12 false negative frozen section diagnoses. It is concluded that when surgeons and pathologists are aware of the limitations of frozen section diagnosis of ovarian tumors, peroperative histologic examination can be worthwhile and prevent under- and overtreatment of gynecologic patients. PMID- 1869094 TI - Expression of carcinoembryonic antigen and ferritin in normal, hyperplastic, and neoplastic endometrium. AB - The distribution of carcinoembryonic antigen (CEA) and ferritin was demonstrated by immunohistochemical method in 95 patients with normal, hyperplastic, and neoplastic endometrium in order to distinguish among these conditions. Fifteen patients with normal endometrium (NE), 28 with hyperplasia (AH), 12 with atypical hyperplasia (AAH), and 40 with endometrial carcinoma (CA) were studied. Paraffin section tissues were subjected to immunostaining according to the avidin-biotin complex method. CEA was found in 33% of NE cases, 46% of AH, 75% of AAH, and 83% of CA (P less than 0.01). Ferritin was not detected in any case of NE; however, it was detected in one case (4%) of AH, in one case (8%) of AAH, and in 88% of CAs (P less than 0.001). Both tumor markers exhibited a heterogeneous staining pattern, and for a given histologic hyperplastic or malignant lesion, corresponded to several phenotypes. There was no significant correlation between clinical stage or tumor grade and CEA or ferritin expression. In conclusion, ferritin seems to be a better biological marker than CEA in distinguishing between hyperplastic and neoplastic endometrial lesions and it is also more reliable than CEA for endometrial malignancy since it was absent in normal and hyperplastic endometria. PMID- 1869095 TI - Early stage I adenocarcinoma of the uterine cervix: treatment results in patients with tumors less than or equal to 4 cm in diameter. AB - Between 1965 and 1985, 160 patients had initial treatment at the M. D. Anderson Cancer Center for Stage I adenocarcinoma of the uterine cervix less than or equal to 4 cm in diameter. Of these patients, 84 were treated with radiation therapy (RT) alone, 20 were treated with external and intracavitary radiation followed by total hysterectomy (R + S), and 56 were treated with radical hysterectomy (RH). Survival rate was strongly correlated with tumor volume (P = 0.0008), lymphangiogram findings (P = 0.01), and tumor grade (P = 0.0018). Patients with a normal-appearing cervix or a small visible or palpable tumor that did not expand the cervix more than 3 cm had survival and pelvic-control rates of more than 90% after treatment with RH or RT. However, after 5 years, 45% of patients treated with RH for tumors 3-4 cm in diameter had disease recurrence in the pelvis, compared with 11% of patients treated with either RT or R + S (P = 0.025). For patients treated with RH, recurrence was also strongly correlated with findings of lymph/vascular space invasion (P = 0.0004) and poorly differentiated tumor (P = 0.018). Major complication rates were comparable for the three treatment groups. The high rate of pelvic recurrence following treatment with radical hysterectomy alone for patients with tumors greater than 3 cm in diameter, particularly in the presence of lymph/vascular space invasion, poorly differentiated features, and/or positive nodes, should be considered in planning the primary management of patients with Stage I adenocarcinoma of the cervix. PMID- 1869096 TI - Whole abdomen radiation therapy after a short chemotherapy course and second-look laparotomy in advanced ovarian cancer. AB - From April 1983 through December 1989, 42 consecutive patients with diagnosis of epithelial ovarian carcinoma were initially managed by aggressive surgery and three courses of endoperitoneal cis-platinum-based chemotherapy followed by an alternating combination chemotherapy and second-look laparotomy. Patients with residual tumor less than or equal to 2 cm subsequently received whole abdominal radiation therapy (WAR). Twenty-eight patients (42% with no residual disease, 21% with microscopic disease, and 36% with residual disease less than 2 cm) were eligible for WAR. WAR was delivered using an open-field technique up to 22 Gy in 20 fractions followed by a pelvic boost of 18 Gy in 10 fractions. The kidneys were shielded posteriorly at 1100 cGy; hepatic shields were not added. One patient did not complete WAR for lung metastases after 5 radiotherapy fractions. The complete treatment program lasted 8 months (range, 6.8-11). The median follow up of the 28 patients entered into the study was 50 months. Eight patients are alive and disease-free at 5 years. The overall and disease-free survival rates at 5 years are 45 and 30%, respectively. All but 2 patients relapsed within the abdominopelvic cavity and 3 developed brain metastases. Toxic effects, during WAR, required treatment interruption in all but 4 patients: 3 developed a small bowel obstruction requiring surgery and 1 died of surgical complications in complete remission. The poor disease-free survival and the severe toxicity encountered have been valid indications that WAR should be discontinued as a treatment modality in advanced ovarian cancer at our department. PMID- 1869097 TI - Late effects of cisplatin-based chemotherapy on renal function in patients with ovarian carcinoma. AB - While the acute toxicity of cisplatin on renal function is well described, the long-term effects have received little attention in the medical literature. In an effort to examine this important issue, we evaluated the renal function of a group of 60 women with ovarian cancer who received a second-line cisplatin-based chemotherapy program at the Memorial Sloan-Kettering Cancer Center longer than 6 months following the completion of their initial cisplatin-based chemotherapeutic regimen. These patients had not received any cisplatin for a median of 19 months (range, 6-57 months) prior to beginning the second-line program. Only 4 patients (7%) had a serum creatinine value greater than 1.3 mg/dl (upper limit of normal in our laboratory) at the time of initiation of the second-line program. In each case, the serum creatinine was less than or equal to 1.6 mg/dl. An additional 6 patients (10%) had a greater than 50% increase in serum creatinine above the initial baseline value prior to any treatment, but were still within the normal range. Following second-line cisplatin therapy, only 1 of the 60 patients (2%) experienced a serum creatinine rise to greater than 2.0 mg/dl. We conclude that a limited number of patients with ovarian cancer who are long-term survivors following cisplatin-based chemotherapy exhibit evidence of a mild persistent compromise of renal function and, in general, second-line cisplatin can be administered to previously treated patients without the development of serious renal dysfunction. PMID- 1869098 TI - Cytoreduction of diaphragmatic metastases using the Cavitron Ultrasonic Surgical Aspirator. AB - The Cavitron Ultrasonic Surgical Aspirator was used to reduce the volume of diaphragmatic metastases in 33 patients. Thirty patients had epithelial carcinoma of the ovary and one each had tubal adenocarcinoma, papillary peritoneal tumor, and mesothelioma. Twenty-seven patients had Stage IIIC disease, and six had Stage IV. Initially, 13 patients had diaphragmatic disease greater than 15 mm diameter (of any single nodule), and 2 had disease 6-15 mm diameter. After cytoreduction using standard means, 11 patients had disease greater than 15 mm diameter and 2 patients had disease from 6 to 15 mm in greatest diameter. After using the Cavitron, 1 patient had no gross diaphragmatic residual disease, and 30 patients had disease 1-5 mm diameter. No complication resulted from the cytoreduction of diaphragm disease using the Cavitron. The Cavitron Ultrasonic Surgical Aspirator is invaluable to obtain minimal residual disease of diaphragmatic metastases. PMID- 1869099 TI - The accuracy of cervicovaginal cytology in the detection of recurrent cervical carcinoma following radiotherapy. AB - The accuracy of cervicovaginal cytology testing in the detection of recurrent cervical carcinoma was investigated by correlating clinical and histology records with cytology smear results for two groups of patients. All patients had been treated with radiotherapy, with or without pelvic surgery, for carcinoma of the uterine cervix. Abnormal cervicovaginal smear results were present for 45.7% (32/70) of patients with histologically diagnosed recurrent cervical carcinoma including a correct prediction of recurrent cervical carcinoma in 32.8% (23/70) of cases. A cytologic diagnosis of recurrent carcinoma was present for 48.9% (23/47) of cases with local recurrence. The positive predictive value for a histologic diagnosis of recurrent cervical carcinoma after a positive cytology report for a group of 61 patients was estimated to be 98.4%. A cytologic diagnosis of locally recurrent cervical carcinoma preceded clinical signs in 15/61 (24.6%) of cases. These results indicate that although cervicovaginal cytology after radiotherapy for cervical cancer does not have high sensitivity it is a reliable test for the diagnosis of local recurrence. Cytologic examination of the vaginal vault or cervix after treatment may thus provide an early diagnosis of tumor recurrence or persistence, in some cases prior to the onset of clinical signs. PMID- 1869100 TI - Stage III ovarian tumors of low malignant potential treated with cisplatin combination therapy (a Gynecologic Oncology Group study). AB - By serendipity we have had the opportunity to evaluate cis-platin-based chemotherapy in ovarian tumors of low malignant potential (LMP). Optimal (less than 1 cm residual disease) FIGO stage III ovarian carcinomas were randomly assigned to treatment with cisplatin plus cyclophosphamide with or without doxorubicin on a prospective Gynecologic Oncology Group Study. On review by the Gynecologic Oncology Group Pathology Committee, 32 of these cases were determined to represent low malignant potential tumors. Mean age of patients with these lesions was 48 years (range, 25-75 years). After initial cytoreduction, 19 patients had residual disease less than 1 cm and 13 had no residual. Twenty (62.5%) received cisplatin plus cyclophosphamide and 12 cisplatin, cyclophosphamide, and doxorubicin chemotherapy; 75% of patients received six or more courses. Second-look surgery was done in 15 cases; only six were negative. However, with a median follow-up of 31.7 months (range, 1-75), only 1 patient has died; no cancer was found at autopsy. The remaining patients are alive without clinical evidence of disease at a median of 30 months. The need for adjunctive therapy in patients with advanced LMP tumors remains speculative. PMID- 1869101 TI - Evidence for a spatiotemporal cluster of ovarian cancer cases. AB - Personal and lifestyle factors, rather than environmental factors, have been associated with the occurrence of ovarian cancer. An apparent spatiotemporal cluster of ovarian cancer cases was evaluated by comparing the observed and expected number of cases (1978-1988), examining morphologic data, reviewing medical records, and conducting an environmental survey of the study area. A statistically significant excess of ovarian cancer cases was noted (8 cases observed, 3.4 cases expected; P less than 0.025). Seven of the eight cases resided within 0.75 miles of each other at time of diagnosis; six cases were diagnosed within a 5-year interval. A morphologic review, medical record review, and environmental survey did not provide any possible reasons for this excess. It is hoped that this initial report will stimulate reports of similar observations by clinicians and health researchers in an effort to further elucidate etiologic factors in the development of ovarian cancer. PMID- 1869102 TI - The role of partial sigmoid colectomy for debulking epithelial ovarian carcinoma. AB - Forty women underwent partial sigmoid colectomy during cytoreductive surgery for advanced epithelial ovarian carcinoma. Twenty-one (53%) and nineteen (47%) received this as part of primary or secondary debulking procedures, respectively. Fifty-four percent had postoperative residual disease less than 1 cm in largest diameter. Even though multiple surgical procedures were performed in conjunction with sigmoid colectomy, 75% of the patients had no significant postoperative morbidity. Postoperative mortality was 2.5%. Seventy-eight percent avoided permanent colostomy. Despite the above morbidity rate and aggressive postoperative therapy, the median survival for the entire group was only 14.5 months, with no significant differences between groups of patients who were categorized by primary or secondary debulking, histologic grade, amount of preoperative disease, ascites, or extent of postoperative residual disease. Although a partial sigmoid colectomy can be performed with a reasonable morbidity rate as part of debulking for ovarian cancer, and probably provides significant palliation of symptoms from large pelvic tumors, it must be used judiciously in selected patients. PMID- 1869103 TI - Dermatofibrosarcoma protuberans of the vulva. AB - Dermatofibrosarcoma protuberans of the vulva is an uncommon low-grade sarcoma of dermal origin. Although wide local excision is the treatment of choice, microscopic tumor projections beyond the central tumor nodule explain the tumors' propensity for local recurrence. Frozen sections of margins may be useful to ensure complete resection. The following report contributes two additional patients with this uncommon neoplasm. Notably, one of these two had a fibrosarcomatous area within the dermatofibrosarcoma protuberans. This is the second reported case of a fibrosarcoma arising in a dermatofibrosarcoma protuberans of the vulva. PMID- 1869104 TI - Diffuse pulmonary carcinomatous embolization: a rare and fatal manifestation of ovarian cancer. AB - A 44-year-old female presented with dyspnea and lethal respiratory failure secondary to pulmonary embolic carcinomatosis as a manifestation of ovarian serous cystadenocarcinoma. Diffuse involvement of pulmonary arterioles and muscular arteries ranging from 30 to 950 microns in diameter was observed in conjunction with slight dilatation of pulmonary arteries. Vascular intraluminal changes included the presence of free clusters of malignant cells, superimposed thrombosis, varying degrees of eccentric fibromyxoid intimal proliferation with entrapped malignant cells, and luminal obliteration with neovascularization. The pathobiological aspects of this unique manifestation of ovarian neoplasia are discussed. PMID- 1869105 TI - Rapidly progressive squamous cell carcinoma of the cervix coexisting with human immunodeficiency virus infection: clinical opinion. AB - The acquired immune deficiency syndrome (AIDS) has been characterized by aggressive malignancies and infections with unusual presentations. There is a well-documented association between cervical dysplasia and the development of cervical carcinoma, and more recent evidence of an association between cervical dysplasia and HIV infection. The course of coexistent HIV infection and cervical cancer has not been well described. We report a patient with HIV infection and a stage IIIB squamous cell carcinoma of the cervix who, despite adequate treatment, had rapid disease progression as well as metastasis to an unusual iliopsoas muscle site in association with an abscess. As HIV becomes more prevalent in the female population, an increased frequency of rapidly progressive cervical carcinoma may be forthcoming. Improved life expectancy of HIV-infected patients due to modern medication is anticipated, causing a cervical neoplasm to have a more prominent effect on prognosis. Close surveillance with frequent Pap smears and colposcopies as well as aggressive management of cervical dysplasia and carcinoma in HIV-infected patients is suggested as is thorough patient counseling. PMID- 1869106 TI - Tamoxifen-associated endometrial carcinoma in postmenopausal breast cancer patients. PMID- 1869107 TI - [Polydactyly of the hands. Recommendation for expanded classification]. AB - The few anatomical findings summarized in the literature have now been expanded by our own anatomical dissections on four hands of still-born infants with postaxial polydactyly, and by intra-operative microsurgical investigations of 25 polydactylous hands. New experimentally-based knowledge of embryology helps interpret the morphogenesis and specific anatomy of polydactyly. It can be postulated that both the location and definite form of polydactyly are a function of the location and extent of initial excessive cell proliferation and disturbance of cell necrosis in the hand blastema. The conclusive discussion of special findings regarding anatomical structures shows regular pattern formations which lend themselves to a broader classification. The classification of malformations of the hand by Temtamy and McKusick was used as a framework for the classification of polydactyly, whether it was existing as an isolated form or as part of a syndrome. The osteological types I to VI found by Wassel in thumb duplication are confirmed by our anatomical findings. Special coding of anatomical findings enabled us to identify four variants and three forms, depending on the development of the digital palmar arteries and nerves. For the triphalangeal pre-axial fingers and the post-axial fifth finger, the five osteological types described by Muller and those described by Duhamel are increased to ten. Comparison with our anatomical findings shows four variants of these osteological types. For post-axial polydactyly, types XI through XIV, existing in three variants, have been defined. PMID- 1869108 TI - [Ischemic contracture of the forearm and hand. Staging and indications for surgical treatment]. AB - Results of long-term follow up of 66 patients with ischemic contracture of the forearm and hand, all surgically treated in the "Unfallkrankenhaus Hamburg)) between 1961 and 1982, are presented. Whereas ischemic contracture of the forearm flexors resulted mainly from fractures, ischemic contracture of the intrinsic muscles of the hand was most often seen after pressure injuries. All patients in this study presented to us with fully established ischemic contractures. Muscle and nerve damage was retrospectively evaluated according to operative notes, and the degree of damage could be classified into four groups. Most frequently, neurolysis, scar excision and muscle-sliding operations were performed; furthermore, tendon lengthening, tendon transpositions, wrist arthrodesis and nerve grafting were indicated. Results were judged according to twelve separately measured functions, each measurement giving a possible score of three to six points. Muscle-sliding operations result in an improved score regardless of ischemic contracture stage. For a stage 2 contracture, a 20 point improvement can be expected. In stage 1 contracture--presenting with extension deficiency of four or more points--, complete recovery can be expected following a muscle-sliding operation. For isolated muscle injuries, tendon lengthening is recommended. For stage 2 contracture, the transposition of superficial to deep flexor tendons results in the same score as a muscle-sliding operation; however, the transposition procedure should be reserved for special indications. In stage 3 contracture, the muscle-sliding operation is the treatment of choice, with secondary procedures such as tendon transpositions and nerve grafts often being necessary. In stage 4 ischemic contracture, muscle-sliding operations may improve extension deficiency; however, wrist arthrodesis, especially in combination with extensor tendon transpositions, may be beneficial. No experience with free muscle transplantation was made during the study period. PMID- 1869109 TI - [Frostbite in children]. PMID- 1869110 TI - [Vascularized periosteal transplant. A review of a new therapeutic possibility]. AB - The idea of using vascularized periosteal flaps in reconstructing bone defects is more than one hundred years old. Up to now, experimental and clinical results regarding their osteogenic capacity have been a subject of debate. Experimental and clinical studies over the last ten years were able to demonstrate osteogenic capability of such vascularized periosteal flaps, provided the periosteum is well vascularized. To insure intact microcirculation, vascularized periosteal flaps must be freed up by sharp dissection. Small pieces of bone may be removed with the periosteum, whereas the periosteum must remain uninjured. There are many known donor sites in man: the iliac crest, the distal femur, the distal humerus and the tenth rib. There are no reports concerning donor site morbidity. Besides its osteogenic capacity, the periosteal flaps have "shape giving" and "space limiting" functions. The given volume within a periosteal flap rolled into a tube is the basis for the "Concept of the Given Space": the space within the tube defines where bone formation will occur, there being no loss of bone into the surrounding soft tissue. Because of the vascularized periosteal flap's fragility and the good results of other reconstructive procedures for segmental bone defects, there are few indications for extremity reconstruction using periosteal flaps: pseudarthrosis in the upper extremity is one example. In the lower extremity, a combination of vascularized periosteum with conventional and mainly vascularized bone grafts offers interesting possibilities for reconstruction. PMID- 1869111 TI - [Rupture of the tendon of the m. flexor pollicis longus--a rare complication after surgery on the scaphoid bone]. AB - Tendon ruptures in the hand without previous direct trauma are rare. Two cases are reported on with attrition of the flexor pollicis longus tendon. The first tendon rupture was along a dislocated cortico-cancellous bone graft following a Matti-Russe procedure; the second was by attrition over the screw of an AO-plate following internal fixation in scaphoid nonunion. Immediate tendon repair by interposition of a short tendon graft or by transposition of the superficialis flexor tendon of the ring finger is the treatment of choice. Further tendon ruptures can arise if surgical intervention is delayed. PMID- 1869112 TI - Replantation after partial amputation of the hand--two case reports. AB - This is a report on two cases of replantation following partial hand amputation. In both cases, the ratio of anastomosed arteries to veins was 3:2. There were no postoperative complications, including thrombosis. Follow-up was two years ten months and two years. PMID- 1869113 TI - [CT-stereotactic determination of targets for thalamotomy for movement disorders]. AB - The methodology of determining an invisible target by CT-stereotaxy, such as the ventrolateral nucleus of the thalamus, is described. This approach obviates the need for traditional ventriculographic determination of the third ventricle commissures and allows accurate measurement of third ventricular width. Morbidity and length of hospitalization are thereby reduced. PMID- 1869114 TI - [Hospitalization survey of rural family practice]. AB - Data on hospital admissions were recorded in 3 village clinics in central Israel during the period 1977-1986. This period coincided with the introduction of regionalization of hospitals, as well as with the growth of board-certified family practice in Israel. The age-adjusted rate of admission from these 3 villages was 74/1000/year, considerably lower than the national rate of 124/1000/year. There was an abrupt decrease in admission rate in 1983, the year of the doctors' strike, followed by a compensatory rise the following year, mainly for surgical procedures. During the years of the survey hospital stay decreased progressively, but the average of the survey population for the whole period (8.3 days) was greater than that of the national population (5.8 days). Hospital stay was longer in the tertiary hospital center than in regional hospitals. Relatively low admission rates but with relatively long hospitalization may be characteristic of higher quality community care. There were marked demographic differences between the 3 villages. The different age structures and ethnic origins of the populations affected hospitalization trends. However, differences in economic status had no detectable effect. Community-based hospitalization surveys over long periods may be useful in demonstrating changes in morbidity patterns over the years, as well as the effects of changes in the health care system. PMID- 1869115 TI - [Treatment of hemoptysis by bronchial artery embolization]. AB - Major hemoptysis carries with it significant mortality, particularly if major surgery has to be performed during active bleeding. Some patients may not be surgical candidates due to chronic disability or may have diseases that, except for the bleeding, would not require surgical intervention. Bronchial artery embolization is becoming recognized as carrying a lower risk than surgery. It allows immediate hemostasis and long-term control of bleeding in a high proportion of cases. PMID- 1869116 TI - [Munchausen syndrome: need for centralized administrative health-care management]. AB - The clinical picture of Munchausen syndrome is that of feigned or self-induced illness with the aim of being hospitalized and/or receiving unnecessary medical interventions, peregrination from 1 hospital to another, and disruptive behavior when hospitalized. These patients are a danger to themselves and heavily burden inpatient facilities that care for them. We present a case that illustrates the problems of diagnosing and managing such patients. We stress the need for adequate centralization and distribution of the relevant information concerning these patients. PMID- 1869117 TI - [Black widow spider bite in the Negev]. AB - In the 4 years, 1985-88, 9 adults bitten by black widow spiders (Latrodectus inactopus) were hospitalized. The syndrome of lactrodectism, not as yet described from the Negev, was mainly characterized in these patients by restlessness, profuse perspiration, severe abdominal pain and rigidity, and muscular twitching. In addition, in 2 cases there was gastrointestinal involvement, with ileus and gastric dilatation. These unique findings, not as yet reported, may be attributed to the particular type of a venom of the black widow spider in the Negev. All victims recovered with symptomatic treatment. PMID- 1869119 TI - [Heterotopic pancreas and pyloric atresia]. AB - A 2.5 kg female neonate, born after a normal 39-week pregnancy to Arab parents (1st degree cousins), developed unremitting vomiting of gastric contents, not bile-stained. Barium study demonstrated a grossly distended stomach with complete obstruction of the outlet. At laparotomy, pyloric atresia and a heterotopic pancreas located subserosally on the antrum of the stomach were diagnosed. A 3-cm gap was measured between the occluded antrum and the duodenum. Transmesocolic gastrojejunostomy was performed, and oral feeding was started 5 days later. Pyloric atresia and heterotopic pancreas are both rare congenital malformations. To the best of our knowledge, the combination of pyloric atresia and heterotopic pancreas has not previously been reported. PMID- 1869118 TI - [Neurologic complications of primary Sjogren's syndrome]. AB - Primary Sjogren's syndrome has a wide clinical spectrum, ranging from an exocrinopathy to a systemic process and even extending to B-lymphocyte neoplasia. We describe a patient with this syndrome who developed central nervous system involvement manifested by involuntary dystonic movements of the mouth and larynx. We believe that the neurological involvement in this patient is part of his basic disease. Further studies are required to define more accurately the frequency, severity and spectrum of the neurological manifestations associated with primary Sjogren's syndrome. PMID- 1869120 TI - [Pneumothorax in cystic fibrosis: intrapleural instillation of Atabrine]. AB - Intrapleural instillation of quinacrine HC1 (Atabrine) was used to treat spontaneous pneumothorax in 2 young men, aged 26 and 36 years, respectively, with advanced pulmonary disease due to cystic fibrosis. Pneumothorax did not recur until 1 year later in 1 case and 2 years later in the other. This mode of therapy for pneumothorax provides a valuable alternative to surgery for the patient with cystic fibrosis, severe lung disease and marginal pulmonary reserve. Quinacrine sclerosis should be considered for management of pneumothorax in cystic fibrosis because of the high rate of recurrence. However, caution should be exercised since heart-lung transplantation cannot be performed after pleural sclerosis. PMID- 1869121 TI - [Appropriate diagnostic steps for proper clinical evaluation of breast lesions in the community]. PMID- 1869122 TI - [Rate-responsive pacemakers]. PMID- 1869123 TI - [Lymphoma of the colon]. PMID- 1869124 TI - [Indications for bone-mass measurements]. PMID- 1869125 TI - [Mustard gas injuries of the eyes]. PMID- 1869126 TI - [Influence of violence in television programs of viewers' violence--a critical review]. PMID- 1869127 TI - [The Jewish attitude towards the aged]. PMID- 1869128 TI - [Vincent Van Gogh--portrait of a disease]. PMID- 1869129 TI - [Palpitation]. PMID- 1869130 TI - [Violence, suicide and the media]. PMID- 1869131 TI - [Apgar score after delivery: is it adequate?]. PMID- 1869132 TI - [Evaluation of patients with syncope]. PMID- 1869133 TI - [Whither medicine?]. PMID- 1869134 TI - [Injuries of the middle face. Proceedings of the 40th annual meeting of the German Society for Mouth, Jaw and Facial Surgery. Innsbruck, 1990]. PMID- 1869136 TI - [Treatment concept and results of zygomatic impression fractures on the Cologne and Strassbourg hospitals from 1975-1988]. PMID- 1869135 TI - [Formal address on the 40th annual meeting of the German Society for Mouth, Jaw and Facial Surgery]. PMID- 1869137 TI - [Facial asymmetry following zygomatic fractures with special reference to various treatment methods]. PMID- 1869138 TI - [Methods and results of the surgical management of lateral midfacial fractures]. PMID- 1869139 TI - [Technique and results of the surgical treatment of 400 lateral midfacial fractures]. PMID- 1869140 TI - [Mechanism of injury in midfacial fractures in traffic]. PMID- 1869141 TI - [Therapy of isolated zygomatic fractures]. PMID- 1869142 TI - [Differential therapy considerations of the value of various repositioning and fixation methods in massive fractures of the cheek bone]. PMID- 1869143 TI - [Long-term results following use of tissue bank bone in the treatment of zygomatic comminuted fractures]. PMID- 1869144 TI - [Primary reconstruction of the nose in central midfacial comminuted fractures]. PMID- 1869146 TI - [Nasal bone repositioning in the framework of initial management of central midfacial fractures]. PMID- 1869145 TI - [Primary management of the traumatized telecanthus]. PMID- 1869147 TI - [Frontobasal involvement in midfacial fractures. Problems in diagnosis and therapy]. PMID- 1869148 TI - [Fronto-naso-orbital trauma as a joint neurosurgical and orofacial surgical challenge]. PMID- 1869149 TI - [Personal therapy concept in the treatment of craniomaxillary fractures]. PMID- 1869150 TI - [Frontobasal fractures--treatment concept and incidence of late complications]. PMID- 1869151 TI - [Diagnosis of cerebrospinal fluid fistula in frontobasal fractures using iotrolan CT-cisternography]. PMID- 1869152 TI - [Therapy of cerebrospinal fluid fistula in midfacial fractures]. PMID- 1869153 TI - [Changes in the maxillary sinus following midfacial fractures]. PMID- 1869154 TI - [Complications in the maxillary sinus area following midfacial fractures]. PMID- 1869155 TI - [Late radiological and clinical findings in the paranasal sinuses following midfacial fractures treated with osteosynthesis]. PMID- 1869156 TI - [Dento-alveolar injuries of the upper jaw]. PMID- 1869157 TI - [Complications in the treatment of midfacial fractures]. PMID- 1869158 TI - [Midfacial fractures in trauma patients of the Innsbruck Department for Mouth, Jaw and Facial Surgery from 1982-1988 with special reference to winter sports injuries]. PMID- 1869159 TI - [Amaurosis following surgical management of orbital floor fractures--an unforeseeable complication?]. PMID- 1869160 TI - [Blindness as a complication following surgical orbital floor revision. Consequences for the surgical procedures]. PMID- 1869161 TI - [Neurological and ophthalmological late sequelae following fractures of the zygoma-orbital area]. PMID- 1869162 TI - [Acuminate orbit syndrome--complications of upper midfacial fractures]. PMID- 1869163 TI - [Flash-evoked visual potentials in patients with craniofacial fractures]. PMID- 1869164 TI - [Therapy of optic nerve lesions in midfacial fractures]. PMID- 1869165 TI - [Results of surgical intervention in traumatic orbital syndromes]. PMID- 1869166 TI - [Somatosensory evoked potentials in the diagnosis and expert assessment of traumatically-induced lesions of the infraorbital nerve]. PMID- 1869167 TI - [Traumatic carotid artery-cavernous sinus fistula]. PMID- 1869168 TI - [Disarrangement of the profile following midfacial fractures. Cephalometric analysis and sequelae for therapy]. PMID- 1869169 TI - [Occlusal disorders as possible sequelae of midfacial plate osteosynthesis]. PMID- 1869170 TI - [Trauma-induced acute inflammation of the orbit]. PMID- 1869171 TI - [Conventional roentgen diagnosis in midfacial trauma]. PMID- 1869172 TI - [Mucocele formation as a late complication following trauma in the paranasal sinuses area]. PMID- 1869173 TI - [Therapy of orbital floor fractures]. PMID- 1869174 TI - [Ophthalmologists' contribution to fractures of the orbital walls]. PMID- 1869175 TI - [Orbital floor fracture. Diagnosis, differential indication and technique of surgical management]. PMID- 1869176 TI - [Localization and extent of orbital floor fracture and indication for covering of the defect]. PMID- 1869177 TI - [Orbital floor reconstruction using implants of compact hydroxyapatite ceramic in midfacial injuries]. PMID- 1869178 TI - [Salzburger maxillary sinus endoprosthesis]. PMID- 1869179 TI - [Temporary infra-orbital resection in the treatment of orbital floor fractures]. PMID- 1869180 TI - [Primary reconstruction of the orbital walls]. PMID- 1869182 TI - [Basic and graduated procedures in the roentgen diagnosis of midfacial trauma in relation to degree of severity and localization]. PMID- 1869181 TI - [Revision of the orbital floor in the framework of midfacial traumatology. Results of a prospective, interdisciplinary study]. PMID- 1869183 TI - [Long-term results following orbital floor reconstruction with homologous bone cartilage implants in midfacial fractures]. PMID- 1869184 TI - [Long-term results following management of comminuted and tissue defect fractures of the orbital floor using maxillary sinus tamponade]. PMID- 1869185 TI - [The surgical management of orbital roof lesions]. PMID- 1869186 TI - [Diagnostic and therapeutic aspects in medial orbital fractures]. PMID- 1869187 TI - [Eye movement disorders prior to and following orbital fractures]. PMID- 1869188 TI - [Blow-in fractures--comparison of surgical and conservative therapy]. PMID- 1869189 TI - [Blow-in fractures of the orbit--an indication for emergency surgery]. PMID- 1869190 TI - [In-vivo and in-vitro osteo-induction and cartilage formation by bone morphogenetic protein]. PMID- 1869191 TI - [Autologous tissue substitute from in-vitro cultivated fibroblasts]. PMID- 1869193 TI - [Growth disorders of the facial skeleton following blow-out fractures of the orbital floor and zygomatic fractures in childhood]. PMID- 1869192 TI - [Injuries of the midface in childhood]. PMID- 1869194 TI - [Diagnosis and therapy of lacrimal apparatus injuries in the framework of midfacial trauma]. PMID- 1869195 TI - [Modified intubation technique in the reconstruction of disarranged lacrimal ducts]. PMID- 1869196 TI - [Unusual indications for osteosynthesis plates in midfacial trauma]. PMID- 1869197 TI - [Midfacial osteosynthesis--pretapped screws versus self-tapping screws]. PMID- 1869198 TI - [Bridging-over of 2-walled orbital defects using biological absorbable plastic foil. An animal study]. PMID- 1869199 TI - [Lymphoscintigraphic studies in midfacial fractures]. PMID- 1869200 TI - [The effect of surgical fracture management on midfacial growth. A cephalometric and histological study in young rats]. PMID- 1869201 TI - [Endoscopic findings of the maxillary sinus in recent midfacial fractures]. PMID- 1869202 TI - [Plate osteosynthesis in traumatology of the midface--an improvement?]. PMID- 1869203 TI - [Reconstruction of form and function of the midface complex]. PMID- 1869204 TI - [Treatment of pan-facial fractures]. PMID- 1869205 TI - [Timing of definitive management of severe orbital and midfacial injuries]. PMID- 1869206 TI - [Timing of surgery and lowering of intracranial pressure in patients with severe craniomaxillofacial accidental injuries]. PMID- 1869207 TI - [Rescue and prehospital care of alpine emergency patients]. PMID- 1869208 TI - [Emergency measures in acute hemorrhages due to midfacial fractures]. PMID- 1869209 TI - [Blood loss and tracheotomy in complicated midfacial fractures]. PMID- 1869210 TI - [Therapeutic concept in midfacial fractures]. PMID- 1869211 TI - [Treatment concept of severe midfacial fractures in dentulous and edentulous patients]. PMID- 1869212 TI - [Results of combination neurosurgical and orofacial surgery of fronto-maxillary fractures]. PMID- 1869213 TI - [Anatomical and functional results in midfacial fractures following miniplate osteosynthesis. Prospective study with the aid of an electronic computer-assisted registration system]. PMID- 1869214 TI - [Treatment of midfacial fractures in changing times--a look back and in the future]. PMID- 1869215 TI - [Results of the treatment of midfacial fractures]. PMID- 1869216 TI - [Indications for the use of various osteosynthesis materials in the treatment of midfacial fractures]. PMID- 1869217 TI - [Studies on the therapy of central midfacial fractures with craniofacial wire suspension or miniplate osteosynthesis]. PMID- 1869218 TI - [Miniplate osteosynthesis versus lag screw osteosynthesis in the management of midfacial fractures]. PMID- 1869219 TI - [Management of midfacial comminuted fractures using the Wurzburg titanium miniplate system]. PMID- 1869220 TI - [Results following internal and external fixation of central and centrolateral midfacial fractures]. PMID- 1869221 TI - [Absorbable materials for osteosynthesis in craniofacial surgery]. PMID- 1869222 TI - [Delayed primary management of midfacial fractures]. PMID- 1869223 TI - [Significance of calvaria transplants for reconstructive traumatology of the midface]. PMID- 1869224 TI - [Reconstruction of partial and total midfacial defects following gunshot injuries]. PMID- 1869225 TI - [Timing of the surgical management of zygomatic fractures]. PMID- 1869226 TI - [The role of conservative-surgical therapy of fractures of the lateral midface]. PMID- 1869227 TI - [Positioning and stabilization of dislocated zygomatic fractures]. PMID- 1869228 TI - [Is there a change in the etiology of craniofacial fractures?]. PMID- 1869229 TI - [Intraoperative determination of the position of the zygoma in the surgical treatment of midfacial fractures]. PMID- 1869230 TI - [Miniplate fixation for the stabilization of zygomatic fractures. A report of 220 cases]. PMID- 1869231 TI - [Strohmeyer/Wassmund method of repositioning versus Gillies' elevation. Results of various fracture management concepts of the zygoma]. PMID- 1869232 TI - [Old age and illness--destroying the intolerable?]. AB - The spectacular criminal case of a nurse who because of killing seven old patients in an intensive care ward had been sentenced to jail for 11 years is shown as example of radical thinking in the face of intolerability of serious illness and age. The deficit model of age is on the one hand justly criticized and called invalid, on the other hand negative aspects of age may not be concealed in the face of hedonistic principles of the present epoch. There is no doubt about the monstrosity of the case of the guilty nurse but it may be exemplary for a frequent defensive behaviour against the phenomena of age. If this is right this singular case may be characteristic of common thinking on the unbearable presumption of age. Self defense turning into aggressivity because of foreseeing the own fate of hopeless illness in moribund aged would then have to be seen as a socially significant attitude. PMID- 1869234 TI - [Codeine and dihydrocodeine as substitute and alternative drugs]. AB - There has been an increasing tendency in West Germany since the beginning of the 60s to abuse codeine and dihydrocodeine-containing drugs as substitutes and alternative drugs. This paper will firstly look at this situation from an epidemiological point of view and summarize the chemical and pharmacological effects, the side effects and toxicology of both kinds of substances. On the basis of own case reports the importance of codeine and dihydrocodeine during the development of an addiction of polydrug addicts and opiate addicts has been revealed, analysed and discussed, also with a view to the legal aspects in connection with the issue of treatment by substitution of drug dependents. PMID- 1869233 TI - [Health and psychosocial effects of miscarriage]. AB - The importance of psychosocial consequences of spontaneous abortion is increasingly pointed out. Different studies showed grief responses in about 50 80% of the women and consequences on occupation, martial relation and family life. The most observed long-term consequences are chronical depressive disorders. Unresolved grief in connection with pregnancy loss is to be considered an important risk factor. Immunological studies demonstrated a reduction of T lymphocyte function in grief and depression as a probable cause of a higher disease risk. Further study is required for more precise definitions of long-term effects. Moreover psychosocial help and counseling for the couples after the pregnancy loss could help to prevent serious chronical disorders. PMID- 1869235 TI - ["If one knows the name, one still knows nothing". Comments on a conspicuous and unexplained psychopathologic manifestation]. AB - In this casuistic contribution a female patient is discussed for whom an adequate psychopathological and diagnostic assessment is very difficult to obtain. With the help of Freud's psychoanalysis, Janzarik's Strukturdynamik and the research into altered states of consciousness by Dittrich different interpretations of the cases are provided. PMID- 1869236 TI - [Immunotherapy of chronic Guillain-Barre syndrome with high dose IgG and cyclosporin A. Case report, review of the literature and perspectives]. AB - We report about the three-year treatment of a patient with chronic relapsing Guillain-Barre syndrome (GBS), who, simultaneously, suffered from benign gammopathy. A casual relationship between the two diseases could not be proven, since specific antimyeline antibodies could not be found. Five severe bouts of the disease occurred during the observation period, only the first two relapses, however, showed improvement with cortisone treatment, while the latter did not so. High dosages of 7S-immunoglobuline, by contrast, led to a rapid improvement during each of the subsequent relapses. The additional therapy with ciclosporine A kept the patient free from neurological deficits for more than six months now. The mechanisms of various immunological therapeutic approaches are discussed, particularly as an alternative to plasmapheresis. Our observation, as well as theoretical considerations, suggest the aforementioned immunological treatment being promising in chronic GBS. PMID- 1869238 TI - Prescriptive authority. PMID- 1869237 TI - [Kleine-Levin syndrome]. AB - The Kleine-Levin syndrome is generally considered to be a benign functional disorder of hypothalamic structures. Its onset is usually in adolescence. The most characteristic symptoms are periodic hypersomnia, excessive eating, hypersexuality, irritability and apathy. Associated features are depressive and schizophrenic symptoms. A biological relationship between the Klein-Levin syndrome and endogenous psychoses is discussed. PMID- 1869239 TI - Couriers work at the Safe House in Hazard. PMID- 1869240 TI - My experiences as a literacy tutor in Leslie County. PMID- 1869241 TI - Anti-BLA.36 monoclonal antibody shows reactivity with Hodgkin's cells and B lymphocytes in frozen and paraffin-embedded tissues. AB - A newly developed monoclonal antibody, anti-BLA.36, raised against a Hodgkin cell line, was shown to have reactivity with Reed-Sternberg cells and activated B lymphocytes and appears to be distinct from other antibodies which identify antigens of hematopoietic cells. Anti-BLA.36 was evaluated in B5-fixed paraffin embedded tissue from 16 cases of Hodgkin's disease of various types and 35 cases of non-Hodgkin's lymphomas representative of the different major subtypes. The specificity of anti-BLA.36 was compared with other antibodies that have been used to mark Hodgkin's cells and B lymphocytes: namely, L26, LN-1, Leu-M1 and Ber-H2, as well as UCHL-1, a pan-T lymphocyte marker. In addition, a subset of the cases was evaluated using frozen tissue in order to validate the staining characteristics of anti-BLA.36 as observed in fixed paraffin sections. Anti BLA.36 was found to react with Hodgkin's cells more consistently than the other antibodies used in this panel. The antibody reacted with an antigen on Reed Sternberg cells and their variants (Hodgkin's cells) in all four subtypes of Hodgkin's disease, and with a subset of reactive and malignant B lymphocytes, but not with T lymphocytes. It may, therefore, be useful in the evaluation of non Hodgkin's lymphomas. Finally, this is the first antibody raised to a Hodgkin's cell line which also consistently marks reactive and malignant B cells, but not T cells. The implications of this observation are discussed in relation to the cellular origin of the Reed-Sternberg cell and the overall nature of Hodgkin's disease. PMID- 1869242 TI - Prognostic value of serum beta 2 microglobulin in primary gastric lymphoma. AB - Sixty-eight previously untreated patients with primary gastric non-Hodgkin's lymphoma (NHL) available for analysis, were entered in a study in which the prognostic significance of serum beta 2 microglobulin levels were evaluated. The serum beta 2 microglobulin was the most significant prognostic factor. Patients with high levels (greater than 3.5 micrograms/mL) had a relapse-free survival (RFS) of 36 months, while the median RFS has not been reached in patients with normal levels (p less than 0.001). The 5-year survival was 80 per cent for patients with normal levels, statistically significant when compared to patients with high levels: 38 per cent (p less than 0.001). Serum beta 2 microglobulin should be included in the initial staging of patients with primary extranodal NHL and patients with high levels should be treated more aggressively. PMID- 1869243 TI - Chromosomal abnormalities in adult non-endemic Burkitt's lymphoma and leukemia: 22 new reports and a review of 148 cases from the literature. AB - Tumour cell karyotypes from patients with Burkitt lymphoma (BL) or Burkitt's type leukemia (ALL3) were studied for correlation with survival, bone marrow and cerebral spinal fluid involvement (CSF), human immunodeficiency virus (HIV) serology, and for recurrent cytogenetic abnormalities. The records of 22 patients with BL from our institution and of 148 cases of BL and ALL3 reported in the literature with karyotypes were evaluated for clinical and cytological features. Overall survival was only 28 per cent and 88 per cent of deaths occurred within the first nine months after diagnosis. Those who survived at least 18 months were unlikely to relapse. Age and gender did not significantly affect survival. Patients presenting with advanced Ann Arbor stage, bone marrow or CSF involvement had lower survival rates. The association of translocations involving chromosome band 8q24 with this disease is confirmed. Sixty-two per cent of karyotypes had t(8;14)(q24;q32) translocations; the recognized variant translocations t(8;22)(q24;q11) and t(2;8)(p12;q24) affected 12 per cent and 9 per cent respectively. Seventeen per cent had abnormal karyotypes but no classic translocation. Patients with variant translocations had the poorest survival rates, and those with the classic t(8;14)(q24;q32) did the best. Despite a small sample size, the variant translocation t(8;22)(q24;q11) appeared to occur at an increased frequency in the patients with AIDS. In the entire group, recurrent involvement of chromosome regions 1q2, 6q11-14 and 17p1 suggests that alteration of genes at these loci, B Cell Growth Factor (BCGF) at 1q2 and p53 on 17p, may contribute to the development and progression of this tumour. Similarly, the frequent trisomies of chromosomes 7, 8, 12 and 18 may indicate an effect on tumour cell growth due to increased gene dosage. Trisomy 12 was found in eight tumours, five from patients with AIDS, suggesting that chromosome 12 has a site or gene whose allelic dosage is selected for in AIDS related lymphoma cells. Cytogenetic studies of adult Burkitt lymphoma and leukemia suggest several likely loci for gene alterations that in conjunction with myc translocations can lead to tumorigenesis. PMID- 1869244 TI - In vitro synergistic activity of PDN-IFN alpha and NM + IFN alpha combinations on fresh bone-marrow samples from multiple myeloma patients. AB - The differential staining cytotoxicity (DiSC) assay was used to evaluate the in vitro sensitivity of tumour and normal bone-marrow cells from 21 multiple myeloma (MM) patients to antitumour agents methylprednisolone (PDN), nitrogen mustard (NM) and recombinant interferon alpha-2b (IFN alpha) tested singly and in the combinations PDN + IFN alpha and NM + IFN alpha. Both the PDN-IFN alpha and NM IFN alpha associations were more efficacious than any agents used singly in reducing the percentage of myeloma cell survival. However, whereas NM, alone and in combination with IFN alpha, provoked a severe reduction in normal bone-marrow population, PDN and PDN + IFN alpha induced an increase percentage survival of normal bone-marrow cells. These findings indicate that, at least in vitro, the PDN-IFN alpha combination exerts a great antitumor effect which is not associated with a relevant cytotoxic activity on normal myeloid cells. PMID- 1869245 TI - Etoposide, 6-thioguanine and idarubicin, an oral combination regimen (ETI) for the induction treatment of acute leukemia. AB - Twenty patients with advanced acute leukemia (16 acute myeloid leukemia (AML), three myeloid blast crisis (BC) of chronic myeloid leukemia (CML), one acute lymphatic leukemia) were treated with a peroral regimen consisting of etoposide 80 mg/m2 and 6-thioguanine 100 mg/m2 twice daily for 5 days, and idarubicin 15 mg/m2 once daily for 3 days (ETI). Two AML patients were in first relapse. All the other patients with acute leukemia had a later relapse or were refractory to primary or salvage treatment. One to six ETI cycles were given. Four AML patients achieved remission and one patient with BC of CML entered the second chronic phase. Clearing of the blood of leukemic cells was seen in seven additional patients. Infection was the most common complication, gastrointestinal toxicity was not a major problem. In conclusion, peroral ETI treatment has a marked antileukemic effect even in an advanced disease, and the toxicity is moderate and well acceptable. PMID- 1869246 TI - A commitment to leadership in a time of change. Interview by Mary A. Grayson. PMID- 1869247 TI - Has HCFA "broken faith" with its new physician fee schedule? AB - Physician groups are upset over the proposed new Medicare fee schedule. The RBRVS was to be budget-neutral and equitable; however, MD groups are charging that its implementation will be neither. PMID- 1869248 TI - Two strategies for preventing wrongful termination suits. PMID- 1869249 TI - CFOs: cost-shift pressures will spur health care policy reform. AB - Hospitals are "on the verge of self-destruction" because they are finding it more difficult to shift costs to those few payers who pay full charges, say CFOs. In fact, the inability to continue shifting costs will lead to national health care reform, say members of a panel of CFOs hosted by Hospitals. PMID- 1869250 TI - State managed care initiatives spur Medicaid policy debate. PMID- 1869251 TI - Contract management. Managing for teamwork in clinical contracting. PMID- 1869252 TI - Is regional incineration the answer for waste? PMID- 1869253 TI - Hospital HRIS: finding a system that works. PMID- 1869254 TI - Ten tips for working with retained search firms. PMID- 1869255 TI - Card format deals this annual report a winning hand. PMID- 1869256 TI - Hospitals devise ways to collect outpatient bills. PMID- 1869257 TI - House calls drive aging issues home for MD trainees. PMID- 1869258 TI - High-tech health care: how much can we afford? PMID- 1869259 TI - An appreciation of Robert E. Scully, MD, and an introduction to a symposium in his honor on recent advances in gynecologic pathology. PMID- 1869260 TI - Symposium in honor of Robert E. Scully, MD: Recent advances in gynecologic pathology--part 1. PMID- 1869261 TI - Robert E. Scully, MD: a pathologist's perspective. PMID- 1869262 TI - Robert E. Scully, MD: a clinician's perspective. PMID- 1869263 TI - Ovarian surface epithelial-stromal tumors. PMID- 1869264 TI - Synoptic surgical pathology reporting. PMID- 1869265 TI - Idiopathic myelopathies with white matter vacuolation in non-acquired immunodeficiency syndrome patients. AB - Postmortem examination of 21 patients showed a vacuolar myelopathy resembling that associated with the acquired immunodeficiency syndrome. Underlying diseases included six cases of leukemia or lymphoma, five of carcinoma, three of systemic lupus erythematosus, two of chronic lung disease, and one each of cadaveric renal transplant, cirrhosis, diabetes, hemophagocytic syndrome, and viral encephalitis. Fourteen patients were on long-term steroid therapy and 10 of these also had immunosuppressive chemotherapy. No patient had the acquired immunodeficiency syndrome, although one received blood transfusions in 1978. Signs and symptoms consistent with myelopathy included paraparesis in seven patients, ataxia in one, and bilateral extensor plantar reflexes in one. Microscopic examination showed vacuolation in spinal cord white matter primarily located in posterior and lateral columns. Lipid-laden macrophages and axonal changes were proportional to the severity of the vacuolation, which was severe in five patients, moderate in 10, and mild in six. Eight patients had coexistent viral diseases elsewhere in the central nervous system, but viral-associated antigens or genomic material was not found in regions of vacuolated spinal cord white matter. Although the etiology of these myelopathies is unknown, their association with immune suppression and coexistent viral infection of the central nervous system suggests that an opportunistic viral infection may be important. PMID- 1869266 TI - Familial lobular glomerulopathy. AB - A family with an unusual lobular glomerulopathy is described. Renal tissue from three males and one female in two successive generations was available for review. The glomerulopathy was characterized by a marked lobular accentuation with only a modest increase in mesangial cellularity. Immunofluorescence in two patients showed focal or diffuse staining with immunoglobulins G, A, M, and C3 in the mesangium and along the glomerular capillary basement membranes. Ultrastructural study showed amorphous granular subendothelial material distending capillary loops and mesangial regions. This material accounted for the pronounced lobular accentuation. The patients in this family presented with proteinuria, hematuria, and hypertension. Three of the four patients have sustained cerebral vascular accidents and two have died. This family is compared with a previously reported family that showed similar glomerular pathology. PMID- 1869267 TI - Nine Japanese patients with immotile-dyskinetic cilia syndrome: an ultrastructural study using tannic acid-containing fixation. AB - Respiratory cilia and sperm flagella of nine Japanese patients with immotile dyskinetic cilia syndrome were studied ultrastructurally by using a tannic acid containing fixative. Respiratory cilia from two female patients with Kartagener's syndrome and one male patient with situs inversus and sinobronchitis were completely immotile and lacked both dynein arms. However, approximately 30% of the spermatozoa from the male patient were weakly motile. In four patients with immotile cilia syndrome without Kartagener's triad, immotile respiratory cilia generally lacked the inner dynein arms. Two clinically unusual cases, an 11-year old boy and a 29-year-old woman with prolonged saccharin test, recurrent bronchitis, and bronchiectasia, possessed motile respiratory cilia. Ultrastructurally, both dynein arms were normal, but numerous defective central pairs (more than 50% and 70%, respectively) were seen, and the defect in the second case was similar to the transposition of microtubules reported by Sturgess et al (N Engl J Med 303:318-322, 1980). However, defects in the first case were unique and may be congenital. We propose a new type of dyskinetic cilia syndrome with defective central pairs. Additionally, nasal cilia from a 35-year-old man with immotile cilia syndrome contained excess large singlets within ciliary axonemes consisting of 17 protofilaments. PMID- 1869268 TI - Angiolymphoid hyperplasia with eosinophilia of the tongue: report of a case and review of the literature. AB - Angiolymphoid hyperplasia with eosinophilia has been described mainly in the dermis and subcutaneous tissues of the head and neck, and only occasionally in the oral cavity. A case of angiolymphoid hyperplasia with eosinophilia of the tongue in an 82-year-old man with typical morphologic features is presented. The diagnosis criteria and treatment of this lesion reported in the English literature are also reviewed. PMID- 1869270 TI - Postmortem examination of the brain in acquired immunodeficiency syndrome patients. PMID- 1869269 TI - Colon perforation due to cholesterol embolism. AB - Embolization to the gastrointestinal tract is a common complication of systemic atheroembolism, but is rarely catastrophic. This study describes perforation of the colon with fatal peritonitis in a 65-year-old patient following cholesterol embolization to the intestinal tract. PMID- 1869271 TI - Inguinal lymph node infection with paragonimiasis. PMID- 1869272 TI - Histopathologic and clinical criteria for definition of dysplastic nevi. PMID- 1869273 TI - Role of imaging in the evaluation of pelvic cancer. AB - The last 15 years have witnessed dramatic advances in the detection, assessment, and management of cancer. Progress is due to increased knowledge of the basic biology of cancer, oncogenes, and immunologic mechanisms controlling cancer; a better understanding of the disease and its diagnosis and management; and improved imaging technology. Diagnostic imaging has been revolutionized by the development of microcomputers and television instrumentation, and by technological advances producing better ultrasound transducers, x-ray detectors, and more homogeneous magnetic fields, as well as more precise magnetic coils and better software. At the time that we have come to understand more about cancer prognostic variables, imaging has developed to offer a unique display of a number of morphologic factors such as tumor size, location, depth of invasion, lymph node status, presence of metastases, and overall stage of disease. Just as accurate knowledge of prognostic variables is essential for designing optimal treatment protocols, it is fundamental in rendering a useful radiology report. Because "the first treatment should be the best possible since it has the greatest chance for curing the patient," an assessment of the full extent of cancer prior to the initiation of treatment is mandatory. Two elements in the clinical setting contribute to the ability to capitalize on these advances and breakthroughs: continuing education about progress in the field of oncology, and a motivated team of treatment specialists. This combination of application of new knowledge and technological advances and team work will promote the necessary environment for the conquest for cancer. PMID- 1869274 TI - High-dose chemotherapy and autologous bone marrow support for breast cancer. PMID- 1869275 TI - Three-dimensional conformal treatment: a new frontier in radiation therapy. PMID- 1869276 TI - Treatment of patients with cancer of unknown primary site. AB - Advances in the management and treatment of the large, heterogeneous population of patients with carcinoma of unknown primary site have been achieved by recognizing treatable subsets within this group. Each of these subsets has been thoroughly discussed; Table 10-9 summarizes the treatable subsets and the evaluations necessary for their identification. Even within treatable subsets, treatment data remain limited, and optimal therapy is still evolving. Despite these advances, a large group of patients with relatively insensitive tumors remains. Improved therapy for these patients will probably await therapy breakthroughs in the treatment of non-small cell lung cancer, pancreatic cancer, and the various other GI malignancies, since these tumors represent the majority of occult primary sites. PMID- 1869277 TI - Chemotherapy and the management of locally advanced squamous cell carcinoma of the head and neck: role in larynx preservation. PMID- 1869278 TI - Progress in decreasing cigarette smoking. PMID- 1869280 TI - Clinical Alert: a poor idea prematurely used. PMID- 1869279 TI - Is a mechanism such as the NCI's Clinical Alert ever an appropriate alternative to journal peer review? AB - Responsibly handled, a mechanism such as a Clinical Alert can provide physicians with enough information to deal with the early release of data to the public. The journal peer review system was established primarily as an academic tool to allow publication of scientific work for the purpose of communicating information among scientists and physicians. Since both the number of papers published by an investigator and the quality of the journal publishing them are important to academic advancement, bypassing this system naturally threatens many physicians and scientists. The Clinical Alert, however, served its purpose and was well received by the majority of practicing physicians and the public. In fact, a second Alert was issued by NCI in October 1989 when data became available on the effectiveness of a new adjuvant drug therapy for a common stage of colon cancer (Appendix B) and, at a workshop convened by the National Cancer Advisory Board, where the mechanism of the Clinical Alerts was discussed, it was apparent that most participants felt that maintaining this process was important. In light of the current revolution in biology, the public's interest in receiving the benefits of its financial support of the national research enterprise, and access by the press to both scientific literature and meetings, it seems appropriate for public officials, especially when mandated by Congress, to take the responsibility of releasing some types of data to the public before traditional peer review. Some visible public decision-making process must, however, be used where the pros and cons of early release of a particular data set can be discussed, as was done with the original NCI Clinical Alert.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869281 TI - Genetic predisposition to cancer. PMID- 1869282 TI - Potential innovations in scheduling of cancer chemotherapy. PMID- 1869283 TI - Cellular and molecular aspects of human tumor radioresistance. PMID- 1869284 TI - Metastasis suppressor genes. PMID- 1869285 TI - Active immunization with EPF suppresses the formation of immune ascites in BALB/c mice. AB - The production of early pregnancy factor (EPF) is not confined to pregnancy--EPF has been detected as a product of tumour and transformed cells in vivo and in vitro. In this study, EPF (or an EPF-like substance) was detected also in the serum of BALB/c mice, 7 days after intraperitoneal (i.p.) administration of the mineral oil pristane. Furthermore, EPF was present in serum from mineral oil induced plasmacytoma-susceptible mice throughout the latent period potentially leading to tumour development, peaking around the time neoplastic cells were identified in ascites. Since mineral oil-induced granuloma is essential to development of immune ascites, involvement of EPF in this process was investigated. Active immunization of BALB/c mice with EPF was shown to suppress the production of immune ascites, induced by multiple i.p. injections of antigen in complete Freund's adjuvant. Of the mice immunized with EPF (n = 19), only 47% produced ascites, compared with 94% of mice receiving saline or human chorionic gonadotrophin and 100% of mice receiving keyhole limpet haemocyanin. Further investigations revealed that ascites was only produced in mice that maintained free-circulating EPF. These mice displayed the classic mineral oil-induced granuloma covering the tissues of the peritoneum. In contrast, the serum of mice that did not produce ascites tested negative for EPF and the peritonea of these mice were devoid of the oil granuloma. These studies suggest that EPF is involved in the initiation and maintenance of the inflammatory response of the peritoneum to mineral oil. PMID- 1869287 TI - Effect of high ligand concentration on West Nile virus-specific T cell proliferation. AB - In this paper the phenomenon of suppression of proliferation in vitro of 14 day primed, West Nile Virus (WNV)-specific, murine CD4+ T cells by large numbers of antigen-presenting macrophages and B cells has been investigated. Suppression was apparently not mediated by prostaglandins, as the use of indomethacin in cultures at four times the usual concentration did not reverse suppression. Experiments were designed to evaluate the contribution of major histocompatibility complex (MHC) Class II and nominal WNV antigens in causing suppression of T cell proliferation. Listeria- or thioglycollate-induced macrophages from CBA/H (H-2k) mice, when treated with heat-killed Listeria in vitro for 1 h to maintain or increase, respectively, MHC Class II levels before the addition of alloreactive Iak-specific T cells caused inverse dose-responses; the highest T cell proliferation occurred at a stimulator to responder (S : R) ratio of 0.25 and profound suppression at a S : R ratio of 1 or 2. In contrast, untreated thioglycollate-induced macrophages, which express low MHC Class II levels, gave a direct dose-response with increasing T cell proliferation as antigen-presenting cell (APC) numbers increased. Addition of anti-Ia antibodies (or their Fab fragments) to cultures caused a significant reversal of suppression of anti-WNV T cells imposed by high numbers of Listeria-induced macrophages or 14 day WNV primed B cell APC. Suppression was also reversed by reducing the concentration of WNV antigen. These observations support the notion that the suppression of T cell proliferation observed at high S : R ratios was due to high concentrations of ligand (WNV-derived peptide complexed with Class II MHC) on APC. PMID- 1869286 TI - Serum factors affecting the specificity of anticardiolipin antibodies. AB - The effects were investigated of two pretreatments of human serum and plasma test samples on their subsequent reactivity in the anticardiolipin antibody enzyme linked immunosorbent assay (ACA-ELISA). The first treatment involved heat inactivation of test samples at 56 degrees C for 30 min, a process sometimes used to inactivate samples from suspected human immunodeficiency virus positive individuals. Such treatment significantly increased the IgG ACA unit/mL values of normal sera, but when this effect was examined further, it was found that the increase in binding occurred on both cardiolipin-coated and uncoated wells and was therefore non-specific. Heat inactivation of sera prior to ACA testing should therefore be avoided. The second treatment involved diluting immunoglobulin (Ig)G and IgM ACA-positive sera in normal human serum (NHS) or newborn calf serum (NCS); sera diluted in NHS showed a significant increase in titre, particularly IgM ACA-positive sera. This phenomenon was found to be due to a serum cardiolipin binding cofactor which enhances antibody recognition. The cofactor is heat stable and is present in normal sera (male and female) and also in IgG ACA-positive sera. The binding of a human IgM monoclonal antibody to cardiolipin was not affected by the cofactor. The cardiolipin/cofactor complex may represent the optimal autoantigen/autoimmunogen and a re-appraisal, therefore, of the clinical relevance of antibodies to cardiolipin and other negatively charged molecules is warranted. PMID- 1869288 TI - Arachidonic acid metabolites in normal and autoimmune mice do not influence lymphocyte-high endothelial venule interactions. AB - In peripheral lymphoid organs the number of lymphocytes and the proportion of functional lymphocyte subsets are regulated by multiple factors including the control of lymphocyte migration by selective lymphocyte-high endothelial venule (HEV) interactions. In this study, prostaglandin E2 (PGE2) levels from normal and autoimmune mouse lymph node cells were measured. The contribution of eicosanoids to lymphocyte-HEV interactions in normal (CBA/T6) and autoimmune (MRL/n) mice was examined. There was no association between PGE2 production in normal or autoimmune mice and the age of onset of disease activity in the latter strains. Arachidonic acid metabolites, in particular PGE2 and leukotriene B4 (LTB4), did not have any effects on lymphocyte-HEV binding. Likewise, lymphocytes treated in vivo and/or in vitro with arachidonic acid metabolite inhibitors (acetyl salicylic acid, indomethacin, BW755C) did not alter lymphocyte-HEV binding interactions in both normal and autoimmune mice. No clinical significance could be attributed to lymph node PGE2 production and the age of onset of autoimmune disease. In summary, these findings cast doubt on the role of arachidonic acid metabolites in lymphocyte-HEV binding interactions. PMID- 1869289 TI - Cloning and sequencing of the cDNA for ovine granulocyte-macrophage colony stimulating factor (GM-CSF). AB - Colony-stimulating factors (CSFs) are not only regulators of haemopoiesis but can also enhance the function of mature myeloid cells, and are therefore potential immune adjuvants. By use of the polymerase chain reaction (PCR) with primers based on the bovine granulocyte-macrophage CSF (GM-CSF) sequence, we have amplified the cDNA for ovine GM-CSF, produced from crude mRNA extracted from alveolar macrophages. The PCR product was cloned into pUC119, and electroporated into Escherichia coli. The complete nucleotide sequence of two clones, and the partial sequence of eight others, was determined. At the nucleotide and amino acid levels, the ovine and bovine GM-CSF sequences are 91% and 81% homologous, respectively. PMID- 1869290 TI - Comparative adjuvant action of gamma insulin and alum. PMID- 1869291 TI - In vitro maturation and fertilization of goat oocytes. AB - Goat oocytes were isolated from 3-5 mm diam. follicles. The oocytes with compact cumulus mass were matured and fertilized in vitro. Three different media, viz. modified Krebs-Ringer bicarbonate, Dulbecco's and Ham's F-12 with three different additives (bovine serum albumin, BSA; follicle stimulating hormone, FSH and fetal calf serum, FCS) were tested. The three basal media gave almost similar results with Ham's F-12 being slightly better. Addition of BSA (10 mg/ml) increased the rates of maturation and penetration. FSH + BSA (2.5 micrograms/ml + 10 mg/ml) further enhanced the rates while FCS (10%) proved to be even more effective. In modified Krebs-Ringer bicarbonate and Dulbecco media with additives FCS + BSA, around 60% oocytes matured to metaphase II of which 53% were penetrated by capacitated goat spermatozoa while in F-12 medium 70% reached metaphase II and 63% were penetrated. Ham's F-12 medium with additives FCS + BSA was slightly better for maturation and penetration of goat oocytes in comparison to two other media tested. PMID- 1869292 TI - Adjuvant activity of some nonpyrogenic hydrophobic analogues of muramyl dipeptide in enhancing the primary humoral and cell mediated immune responses in guinea pig model. AB - Five muramyl dipeptide analogues synthesized by derivatization of gamma-carboxyl of D-isoglutamine residue of MDP into alkyl amides or incorporation of lysine residue at the site via epsilon-NH2 function were evaluated for immuno-adjuvant activity. Derivatization of gamma-carboxyl of D-isoglutamine into butyl, octyl and dibutyl residues stimulated delayed type of hypersensitivity (DTH) response, the maximum stimulation being observed with octyl amide. Introduction of lauryl amide residue abolished DTH response. The antibody response was impaired with all the alkyl amide analogues except for the lysyl amide derivative with which the response was higher than MDP. Correlation was observed between DTH response and macrophage migration. PMID- 1869293 TI - Protein profile and stimulation potential of partially purified lectins from two varieties of Phaseolus vulgaris L. AB - Phytohaemagglutinin obtained from P. vulgaris is a commonly used mitogen in lymphocyte cultures. The mitogenic potential of different cultivars of P. vulgaris vary. The present investigation encompasses the characterization of partially purified lectins from two varieties of P. vulgaris on the basis of their protein profile, lymphocyte transformation test by light and scanning electron microscopy and incorporation of radioactive thymidine. PMID- 1869294 TI - A rapid method for evaluation of analgesic and anti-inflammatory activity in rats. AB - Carrageenin (2%) was used to produce edema and hyperalgesia; indomethacin, phenylbutazone, aspirin, ibuprofen, analgin, paracetamol and phenacetin were tested at different doses for anti-inflammatory and analgesic activity in the same rats as the peak for the edema reached at the end of 3rd hr and for the hyperalgesia at the end of 4th hr. Indomethacin, phenylbutazone and ibuprofen reduced edema and increased the pain threshold. Analgin and aspirin increased the pain threshold relatively at a low dose. Paracetamol and phenacetin were inactive in the doses tested. Carrageenin (2%) was observed to possess both phlogistic and allogenic properties. PMID- 1869295 TI - Effect of antiepileptic drugs valproic acid, carbamazepine and ethosuccimide on exploratory behaviour in mice. AB - Valproic acid in 100, 200 and 400 mg/kg doses produced a significant dose dependent decrease in exploratory behaviour, tested as number of head dips on the hole board. In the open field test, control mice entered less number of peripheral squares and more number of central squares on day 4 as compared to day 1 of the test. In the lower doses (100 and 200 mg/kg) valproic acid increased central square entries on day 1 with significant decrease by all doses on subsequent days indicating inhibition of exploratory behaviour. However, in peripheral square entry they followed the same pattern as control mice. Neither carbamazepine (10 and 20 mg/kg) nor ethosuccimide (100 and 200 mg/kg) affected exploratory behaviour in either the hole board or open field test. PMID- 1869296 TI - Thermic response of selective muscarinic agonists and antagonists in rat. AB - Effect of some selective agonists and antagonists of cholinergic M receptor subtypes on rectal temperature was investigated in rats at an ambient temperature of 25 degrees +/- 2 degrees C. Centrally administered acetylcholine (ACh) induced transient hypothermia, whereas the muscarinic M1 receptor agonists, arecholine (ip) and McN-A-343 (McN) (icv), induced sustained and dose-related hypothermia. However, the nonspecific muscarinic receptor agonist, oxotremorine, and physostigmine, induced hypothermia at a lower dose and hyperthermia, accompanied by tremors, at higher doses. The muscarinic M2 receptor agonist, carbachol (icv) also produced a dose-related dual effect, hyperthermia and hypothermia being induced by the lower and higher doses, respectively. The M1 receptor antagonists, scopolamine (ip) and pirenzepine (icv), induced hyperthermia, whereas the M2 receptor antagonists, gallamine (icv) and AF-DX 116 (AFDX) (ip), produced hypothermia. The hypothermic effects of ACh. arecholine, McN, physostigmine, oxotremorine and carbachol were attenuated by scopolamine and pirenzepine. However, although scopolamine also inhibited the hyperthermic and tremorogenic effects of the higher dose of oxotremorine, it had a synergistic effect with the hyperthermia-inducing higher dose of physostigmine. AFDX attenuated the hyperthermic effect of the lower dose of carbachol, indicating that it was M2 receptor-mediated. Hemicholinium, an ACh synthesis inhibitor, had a transient hypothermic effect followed by slight hyperthermia. However, it markedly antagonized the hypothermic effects of gallamine and AFDX, indicating that their effects were dependent upon the availability of neuronal ACh. The results indicate that cholinergic hypothermia is a function of central muscarinic M1 receptors, with the M2 receptors serving as automodulators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869297 TI - Effect of selective muscarinic receptor agonists and antagonists on active avoidance learning acquisition in rats. AB - Effect of some selective muscarinic receptor agonists and antagonists was investigated on learning acquisition in an active-avoidance paradigm in rats which records an anticipatory conditioned avoidance apart from the classical conditioned avoidance response. The muscarinic M1 agonists, arecholine, pilocarpine and McN-A-343, facilitated learning acquisition, which was attenuated by the selective M1 antagonist, pirenzepine. On the other hand, M2 receptor agonist, carbachol, and physostigmine, induced a dose-related dual response, with lower doses retarding and higher doses facilitating the learning acquisition. The former effect was attenuated by gallamine, a muscarinic M2 antagonist, while the latter response was inhibited by pirenzepine, indicating that these putative M2 receptor agonist lose their receptor specificity on dose increment. The selective M2 receptor antagonists, gallamine and AF-DX 116, facilitated learning acquisition, which was inhibited by pirenzepine and the acetylcholine synthesis inhibitor hemicholinium. The results support the cholinergic hypothesis of learning and memory and indicate that M1 receptor agonists and M2 receptor antagonists are likely to prove beneficial in memory deficits. The data also indicates that the clinical dose of some drugs, like physostigmine, needs to be carefully established for optimum therapeutic benefit. PMID- 1869298 TI - Individual and combined toxicity of common pesticides to teleost Puntius conchonius Hamilton. AB - Individual and combined toxicity of three pesticides, endosulfan, phosphamidon, and aldicarb was evaluated in P. conchonius. The 48 hr LC50 was 21.36 and 446.5 ppm respectively for endosulfan and phosphamidon. When tested jointly, 48 hr LC50 for different ratios of these pesticides were 0.332 (IE:3P), 0.224 (IE:1P), and 0.178 ppm (3E:1P). The cotoxicity coefficients for these combinations were 1793, 3986, and 10009, respectively. An equitoxic mixture of endosulfan, phosphamidon, and aldicarb yielded a 48 hr LC50 of 130.5 ppm. An enhanced toxic impact is indicated when the pesticides are present together rather than as individual compounds. PMID- 1869299 TI - A simple method to quantify maturation of wound collagen. AB - While investigating the effect of NSAIDs and Zn(II) (NSAIDs)2 complexes on healing of dead space wounds we found that both NSAIDs and Zn(II) (NSAIDs)2 reduced collagen content to a comparable extent yet only NSAIDs reduced breaking strength (BS) of wounds. Since collagen content and maturation are the two important determinants of BS it was obvious that only NSAIDs reduced maturation. A simple method to assess the extent of maturation in available collagen is being reported in the present study. While all NSAIDs significantly reduced the maturation of collagen, Zn(II) (NSAIDs)2 complexes per se did not affect the maturation of collagen of 10-day old. Though, chronologically, granulation tissues obtained from both the treated groups were 10-day old, maturation-wise the age of NSAIDs and Zn(II) (NSAIDs)2 treated granulation was 6 and 12 days respectively. PMID- 1869300 TI - Osteoinductive property of fluoride impregnated decalcified allogeneic bone matrix. AB - Present study was carried out in order to explore the ability of a bone graft decalcified as well as fluoridated to form new bone when put in the rectus abdominis muscle of rabbit. A total of 66 implants placed inside the pouches created in rectus abdominis muscle of rabbits were followed for 2 to 20 weeks. Radiologically decal implants formed bone in 74% cases and fluoridated implants in 68%; whereas histologically 86% of decalcified and 80% of fluoride impregnated decal bone matrix showed evidence of bone induction. It is concluded that fluoride impregnation does not enhance the osteogenic potential of a decal bone matrix. PMID- 1869301 TI - Effect of garlic supplementation to cholesterol-rich diet on development of atherosclerosis in rabbits. AB - Feeding of cholesterol-rich diet in male rabbits resulted in increased levels of cholesterol in plasma, aorta and liver and total lipids, phospholipids, free fatty acids in aorta and liver. Garlic supplementation to this diet suppressed these effects but their levels were still higher as compared to control rabbits. The plasma fibrinolytic activity which was decreased on cholesterol feeding was considerably increased when this diet was supplemented with garlic. There was increase in the activity of phospholipase in the cell-free supernatant of aorta and liver and decrease in the activity of cell-free supernatant NADH dehydrogenase of aorta when atherogenic diet was supplemented with garlic. Histopathological studies of aorta, liver and heart supported biochemical studies and indicated retardative effect of garlic on the development of atherosclerosis. PMID- 1869303 TI - Effect of fluvalinate, a synthetic pyrethroid on learning and memory traces in rats. PMID- 1869302 TI - Effect of dimethoate and fenvalerate on conditioned avoidance and passive avoidance responses. AB - Dimethoate at 24.75 and 49.5 mg/kg (i.e., 1/10 and 1/5th LD50 respectively) impaired the learning process and retrieval of memory in rats while it did not affect permanent memory. Fenvalerate / 10.12 and 20 mg/kg (i.e., 1/20 and 1/10th LD50 respectively) had no effect on learning process, retrieval of memory and permanent memory traces. PMID- 1869304 TI - Variations in the cytoplasmic region account for the heterogeneity of the chicken MHC class I (B-F) molecules. AB - Molecular variation among major histocompatibility complex (MHC) class I (B-F) proteins from B-homozygous chickens is apparently caused by C-terminal variation. Analysis of the total B-F protein pool revealed substantial heterogeneity with two or three molecular mass constituents, each being comprised by several isoelectric focusing variants. This heterogeneity could not be reduced by enzymatic deglycosylation. By contrast, proteolytic removal of a small (Mr 1000 4000) fragment from the alpha chain resulted in the generation of a Mr 36,000 fragment, common to all the molecular mass variants. Unlike the parent proteins, the Mr 36,000 fragment derived from isolated variants yielded identical, simple patterns in two-dimensional gel electrophoresis and identical finger prints in peptide mapping. This, together with N-terminal amino acid sequencing, as well as comparison of hydrophobicity properties of fragments obtained by gradual proteolytic digestion, indicated that the small peptide responsible for the major B-F heterogeneity was situated in the intracellular, C-terminal part. PMID- 1869306 TI - A distinctive change in odortype determined by H-2D/L mutation. PMID- 1869305 TI - Interaction of CD4 with HLA class II antigens and HIV gp120. AB - We have developed a cellular adhesion assay in which B lymphocytes expressing HLA class II antigens form rosettes with COS cells expressing high levels of cell surface CD4 upon transient transfection with a CDM8-CD4 plasmid construct. The assay is specific, quantitative, and overcomes the difficulties encountered with a previously described system using an SV40 viral vector. Rosette formation was inhibited by a series of CD4- and HLA-DR-specific antibodies, as well as by human immunodeficiency virus (HIV) gp 120, and a synthetic peptide derived from part of its binding site for CD4 (amino acid residues 414-434), but not by a variety of other effectors, including several soluble CD4 derivatives. The comparison of this pattern of inhibition with those observed in other systems further emphasizes the great similarity, but incomplete identity, in the CD4 binding sites for HLA class II antigens and HIV gp120, and supports a model in which CD4 is considered as an allosteric servomodulator of T-cell adhesion and function which probably is induced to interact with HLA class II antigens when associated with the Tcr/CD3 complex. PMID- 1869307 TI - Genetic mapping of a male germ cell-expressed gene Tpx-2 to mouse chromosome 17. PMID- 1869308 TI - Nucleotide sequence of a cDNA clone of the horse (Equus caballus) DRA gene. PMID- 1869310 TI - [Endodontic retreatment. Following a clinical case]. PMID- 1869311 TI - [Ethnic oro-labial mutilation]. PMID- 1869312 TI - [Pedodontics in Bouche-du-Rhone. Results of a study of dental care for an urban child population]. PMID- 1869309 TI - The nucleotide sequence and evolution of ovine MHC class II B genes: DQB and DRB. AB - The nucleotide sequences of one Ovar-DQB gene, excluding exon 1 and parts of the introns, and one Ovar-DRB pseudogene are presented. The structure of the Ovar-DQB gene is typical of a major histocompatibility complex (MHC) class II B gene and demonstrates considerable sequence similarity with that of humans including such characteristics as the less common polyadenylation signal, ATTAAA. The ovine sequence has a typical 5' acceptor splice signal for exon 5, thus potentially encoding a full length cytoplasmic tail. The Ovar-DRB gene identified in this study was found to be a pseudogene, lacking a defined exon 2 and containing premature termination codons in both exons 3 and 4. The 3' donor splice site of exon 3 is also atypical. A purine-pyrimidine microsatellite repeat, (dC.dA)15, in the 3' region of the pseudogene may be a hotspot for recombination within the ovine DR subregion. PMID- 1869313 TI - [Ligamentary laxity and intracapsular dysfunction of the TMJ. Early diagnosis after orthodontic treatment]. PMID- 1869314 TI - Male infertility due to asthenozoospermia and flagellar anomaly: detection in routine semen analysis. AB - Major monomorphous teratozoospermia, due to sperm tail structural anomalies, were detected in 42 out of 4231 infertile patients during routine semen analysis. The flagella were very short or absent in 16 cases, shortened with thickness irregularity in 18 cases, and of normal length with diameter anomalies in eight cases. These syndromes were always associated with poor forward motility, while mobility and penetration into human cervical mucus were sometimes impaired only partially. With good sperm smears and an experienced observer, the diagnosis could be made without the need for electron microscopic analysis. All the affected patients were sterile and several syndromes could have been transmitted genetically. PMID- 1869315 TI - The effect of A23187 concentration and exposure time on the outcome of the hamster egg penetration test. AB - We investigated the conditions required to enhance the performance of human sperm in the hamster egg penetration test with the free acid form of A23187. The best performance was observed after stimulation with 2 microM A23187 for 1 h when the median penetration rate with sperm from fertile donors was 100% of eggs with 5.8 decondensed sperm heads/egg. Extending the stimulation period with 2 microM A23187 to 2 or 3 h, resulted in a progressive decrease in the penetration rate. In the absence of A23187, the penetration rate was lower (0.7 decondensed sperm heads/egg after 1 h) but increased with stimulation time. A similar picture was observed with sperm from patients taken for an IVF programme. For a pool of cryopreserved semen, the coefficient of variation of the penetration rate after stimulation with 2 microM A23187 for 1 h, expressed as decondensed sperm heads/egg, was 11% within and 20% between assays. There was no correlation between the outcome of the hamster egg penetration test and the percentage motility, velocity or lateral head displacement of the sperm measured after the same stimulation regime. However, in IVF patients the initial velocity and lateral head displacement of the sperm (zero time) were correlated with the best result from the hamster egg penetration test (r = 0.62 and 0.57 respectively). No motility changes characteristic of capacitation were detected. We conclude that stimulation with 2 microM A23187 (free acid) for 1 h prior to the addition of the zona free hamster eggs can produce a high penetration rate with fertile samples and provides a convenient and robust protocol for the assay. However, when carried out in this way the test does not assess the ability of the sperm to capacitate. PMID- 1869317 TI - Sperm count and motility influence the results of human fertilization in vitro. AB - In order to select sperm characteristics that can predict the outcome of in-vitro fertilization-embryo transfer (IVF-ET), semen samples delivered in conjunction with this treatment were studied carefully. We have analysed these data retrospectively in relation to the outcome of treatment. Ninety-one couples were treated for tubal infertility by IVF-ET. Fifteen women became pregnant. Sperm were isolated from semen using a swim-up technique and in most cases 40-80 x 10(3) (range 20-120 x 10(3)) motile sperm per ovum were used for insemination. The couples were divided into three groups: group A who achieved pregnancies, group B who achieved cleaved ova but no pregnancies, and group C who achieved no ova that were cleaved 48 h after oocyte recovery. Comparisons between these groups showed that some characteristics of the native semen samples and the swim up preparations were significantly different: the sperm concentration (P = 0.001) and total sperm count (P = 0.003) in the native sample, the number of sperm recovered during 30 min of swim-up (P = 0.001), and the specific progressive motility of sperm in the swim-up preparation, both at the time of insemination and on each day, up to 5 days thereafter (P = 0.002-0.028). No pregnancy was achieved with a sperm concentration below 26 x 10(6) ml-1 in the native sample. Some of the sperm characteristics studied in this paper may be of value in the pretreatment evaluation for IVF treatment. PMID- 1869316 TI - Testicular steroidogenesis in X/X sex-reversed mice. AB - The sex-reversed X/X Sxr mouse is phenotypically male but lacks germ cells. This provides the opportunity to examine Leydig cell function in the absence of a normal germinal epithelium and without experimental manipulation of the testis. Serum testosterone was lower in Sxr males compared to normal (X/Y) males but there was no significant difference in intratesticular testosterone levels. Serum immunoactive and bioactive luteinizing hormone levels were not significantly different between the two groups. Injection of human chorionic gonadotrophin (hCG) increased intratesticular testosterone in Sxr males more than in normal males although there was no difference in serum testosterone levels. These differences in circulating and intratesticular testosterone levels may be related to reduced blood flow through the Sxr testis. Both basal and hCG-stimulated androgen production by whole testes in vitro were not significantly different between normal and Sxr males. Androgen production per Leydig cell, however, was significantly reduced in cells from Sxr males; this difference was apparent under basal conditions and following stimulation with hCG, dibutyryl cyclic AMP, 22R hydroxycholesterol or pregnenolone. Results show that in the absence of a normal germinal epithelium there is a decrease in the steroidogenic capacity of the Leydig cells although steroidogenesis by the whole testis is not impaired significantly. PMID- 1869318 TI - Successful treatment of infertility due to retrograde ejaculation by instillation of serum-containing medium into the bladder. A case report. AB - The treatment of infertility caused by retrograde ejaculation has often been ineffective. The unphysiological composition of the urine is the main reason complicating the recovery of motile sperm. We describe a case of retrograde ejaculation caused by a congenital defect of the internal sphinchter muscle of the urinary bladder. In this case, motile sperm were only recovered if the bladder had been filled previously with artificial culture medium (Ham's F-10) supplemented with the patient's own serum. Two pregnancies followed intrauterine insemination with sperm recovered in this way. PMID- 1869319 TI - Origin of the human seminal plasma motility inhibitor within the reproductive tract. AB - The origin of a human seminal-plasma sperm-motility inhibitor was investigated. Seminal vesicle and prostatic fluids, testes, epididymides, prostate and seminal vesicles were collected from young cadavers. The motility inhibitor, as measured by its capacity to block the motility of demembranated-reactivated sperm was present in significant amounts only in seminal vesicle fluid. The level of biological activity in this fluid was 13.6-fold higher than in seminal plasma. However, the concentration of motility inhibitor, as measured by ELISA, using an antibody generated against the motility inhibitor purified from human seminal plasma, was only 1.54-fold higher than in seminal plasma. The data suggest that the seminal plasma motility inhibitor originates from seminal vesicle fluid and that it is processed into a nine-fold less biologically active form when seminal vesicle fluid is mixed with other accessory gland secretions at ejaculation. PMID- 1869320 TI - Variation of semen quality in normal men. AB - To examine the amount of variability in semen analysis results and whether there is any effect of season, 673 specimens provided by seven normal, healthy men (61 205 specimens/subject) over 72-324 weeks were assessed for sperm concentration, ejaculate volume, motility and motility index. Noticeable sample to sample variations were found. The largest proportion of the overall variance was due to within-subject differences, e.g., sperm concentration (54%), ejaculate volume (59%), percentage motility (96%) and motility index (74%). Although changes in semen-analysis results occurred over the year, no consistent trend was seen. No evidence was found to suggest that the differences were due to modifications of the methods employed by the laboratory, or to the change of season. PMID- 1869321 TI - Consequences of restenosis after coronary angioplasty. AB - The consequences of restenosis after angioplasty were evaluated in 466 patients who had coronary angiography 3 to 12 months after successful coronary angioplasty and were followed long term. The 236 subjects with restenosis resembled the 230 without restenosis with respect to age, sex, presence of multivessel disease, mean ejection fraction, prior myocardial infarction, prior coronary artery bypass grafting, and completeness of revascularization. The 5-year relative risk of revascularization for patients with restenosis markedly exceeded that for patients without restenosis. The relative risk of repeat angioplasty in the former group was 4.26 times that in the latter group (95% confidence interval, 2.80 to 6.51), and the risk of coronary artery bypass grafting in patients with restenosis was 3.68 (95% confidence interval, 2.16 to 6.28). There was no difference between the 2 groups in the relative risk of myocardial infarction or death. When the completeness of revascularization was considered, patients with incomplete revascularization and restenosis had the worst outcomes, with 50% needing coronary artery bypass grafting within 5 years. Early restenosis markedly increases the probability of revascularization, but it has little effect on infarction or mortality. Even when early restenosis is absent, further revascularization procedures are still frequent. A solution to the problem of restenosis might reduce by half the need for revascularization during the subsequent 5 years. PMID- 1869322 TI - The continuity equation tested in a bileaflet aortic prosthesis. AB - The continuity equation is valid for a population of aortic valves, but its accuracy in individual valves is uncertain. In bileaflet prostheses, obstruction to forward flow is small and individual variability in opening behaviour is minimal. In these valves, the area of the effective orifice should be close to that measured by the manufacturer. A total of 57 patients aged 58 +/- 11 years were studied at a mean of 3.6 months after implantation with a CarboMedics aortic prosthesis. Nine had additional implants in the mitral position and all prostheses were clinically normal. Peak subaortic and transaortic velocities were averaged over 5 beats. The area of the effective orifice was significantly different between the four diameters (P less than 0.00001), and the correlation between the effective and measured area of the orifice was moderate (rs = 0.73, P less than 0.00003). The 95% range for the differences between individual pairs of values, however, was 0.16 +/- 0.61 cm2. Discrepancies probably arose in the estimation of subaortic cross-sectional area and subaortic velocity. Thus, the continuity equation may be inaccurate in an individual prosthetic valve when functioning normally. PMID- 1869323 TI - Profile of coronary arterial disease in diabetic patients undergoing coronary arterial bypass grafting. AB - Diabetics are believed to have more extensive and diffuse lesions of the coronary arteries in presence of coronary arterial disease. We studied prospectively 52 diabetics with coronary arterial disease who underwent coronary arterial bypass grafting and evaluated their pre-operative symptomatology, angiographic appearance of coronary arteries, coronary arterial dimensions as assessed at surgery, and the post-operative complications. These were compared to 52 age and sex matched non-diabetic controls undergoing surgery during the same period. There was no statistically significant difference in the incidence of pre operative symptomatology or frequency of myocardial infarction in the two groups. Left ventricular angiographic findings were also comparable, as was the observation on the extent and severity of coronary arterial disease as assessed by angiography and at surgery. Hence, we recommend coronary arterial bypass grafting to diabetics with the same criteria as are applied to non-diabetics, confident that there will be no added morbidity and mortality. PMID- 1869325 TI - Transoesophageal echocardiographic assessment of primum, secundum and sinus venosus atrial septal defects. AB - We compared the ability of transthoracic and transoesophageal echocardiography to determine the presence and site of an atrial septal defect and associated anomalous pulmonary venous connexions in 13 school age children (aged 5 to 15 years) and 12 adults (aged 25 to 68 years). Transthoracic echocardiography detected atrial septal defects in 12 children and 6 adults. Transoesophageal echocardiography confirmed the position of 16 (13 secundum, 3 primum) of these 18 defects but altered the diagnosis from a secundum defect to a sinus venosus defect in one and from a sinus venosus defect to a high secundum defect in another. In addition to these 18, transoesophageal echocardiography diagnosed a defect in 5 adults (3 secundum and 2 sinus venosus defects) and 1 child (secundum defect). In an adult with inconclusive transthoracic findings, transoesophageal echocardiography enabled clear visualisation of the atrial septum and excluded an atrial septal defect. Transoesophageal echocardiography showed anomalous attachment of a pulmonary vein into the region of a sinus venosus defect (n = 3) but did not show anomalous connexions to the superior caval vein (n = 3) or the inferior caval vein (n = 1). Transoesophageal echocardiography provides a reliable method of diagnosing or excluding an atrial septal defect in patients with inconclusive transthoracic findings and is of particular diagnostic value in sinus venosus defects. PMID- 1869324 TI - Long-term outcome for children with acute renal failure following cardiac surgery. AB - Acute renal failure requiring dialysis occurred in 34 children (2.9%) following cardiac surgery over a five year period. 17 children (50%) recovered renal function with 11 (32%) long-term survivors. The long-term outcome for the survivors, in terms of renal function, was studied from 1 to 5 years after their episodes of acute renal failure. Three children had significant abnormalities of renal function despite normal urinalysis. Detailed assessment of renal function is advocated for children who survive acute renal failure following cardiac surgery. PMID- 1869326 TI - Cerebral arteriovenous malformations in the neonate: clinical presentation, diagnosis and outcome. AB - We reviewed the diagnostic features and clinical outcome of 7 consecutive neonates who were diagnosed to have cerebral arteriovenous malformations. All presented with cardiac failure, and a cranial bruit was heard in 6/7 patients. There was electrocardiographic evidence of myocardial ischemia in 6 patients. The diagnosis was established at cardiac catheterization, or by cardiac and cranial ultrasound. Three patients died of heart failure before definitive treatment. Despite early intervention, three of the remaining four patients died either during or immediately after embolization or ligation of the fistula. A cerebral arteriovenous malformation is a rare cause of neonatal heart failure. Despite prompt recognition and aggressive treatment, the outlook for symptomatic neonates is poor. PMID- 1869327 TI - Paucity of risk factors in women with angina and normal coronary angiograms. AB - A significant proportion of women who undergo coronary arteriography for investigation of angina have normal coronary angiograms. We wanted to test the hypothesis that screening women with risk factors for coronary arterial disease would reduce the need for subjecting them to this invasive procedure. Comparisons were made between 100 women with normal coronary angiograms and 100 women with angiographic evidence of coronary arterial disease. Both groups had presented with angina and had undergone coronary angiography in 1985 or 1986. Women with angina and normal coronary angiograms had fewer risk factors than those with coronary arterial disease. They were younger (mean 49.0 and 55.9 years, respectively), had less severe angina on presentation (atypical or mild angina: 35% vs 16%), were less likely to have a family history of myocardial infarction (12% vs 53%), were more likely to have never smoked cigarettes (64% vs 13%), and fewer of them had a serum cholesterol in excess of 6 mmol/l (36% vs 64%). Five independent predictors of coronary arterial disease were identified; family history, myocardial infarction, age, hypertension and smoking habit. No women with angina and abnormal coronary angiograms were found to be free of risk factors, whereas 42% of women with angina and normal coronary angiogram were free of risk factors. The data suggests that coronary angiography will probably be normal in women with angina who are free of risk factors. PMID- 1869328 TI - The use of associated propafenone in patients with amiodarone-resistant ventricular tachycardia. AB - To clarify the risk-benefit ratio involved in association of antiarrhythmic drugs, a combined therapy of amiodarone and propafenone was tested by means of continuous electrocardiographic monitoring, analysis of levels of the drug in the plasma and programmed electrical stimulation in a selected group of 10 patients who had left ventricular dysfunction and spontaneous relapses of sustained ventricular tachycardia despite treatment with amiodarone. Induction of sustained ventricular tachycardia, possible in each case during treatment with amiodarone, was suppressed after addition of propafenone in 2 patients (responders), who had the best ejection fractions of the entire group (greater than 45%). Worsening of spontaneous tachycardias developed in 4 cases during the combined therapy. These ventricular arrhythmias, although generally at a low rate, sometimes had the potential to degenerate into ventricular fibrillation and disappeared after both discontinuation of propafenone or increase of its dosage (1 patient). Of the six cases undergoing chronic combined treatment, only the responders to premature electrical stimulation were completely protected from recurrences of arrhythmia. Three cases, on the other hand, needed permanent endocardial pacing for symptomatic bradyarrhythmias. The combination of treatment with amiodarone and propafenone, although potentially useful in limiting dosages of and toxicity from amiodarone, is frequently associated with undesirable, and occasionally has severe, side-effects. The best candidates for this pharmacological association seem to be patients without severely depressed left ventricular function who have a greater probability of not presenting the inducibility of ventricular tachycardia after the addition of propafenone to the regimen for treatment. PMID- 1869329 TI - Levels of IgE in the serum of patients with coronary arterial disease. AB - Because previous studies have shown that mast cells can be activated by IgE mediated mechanisms to release potent mediators which affect coronary blood flow, we measured serum IgE levels in 156 patients with coronary arterial disease and in 53 healthy controls (27 men, 26 women, mean 54 years). Patients were classified into 3 groups according to well established criteria as having stable angina pectoris (28 men, 15 women, mean 58 years), unstable angina pectoris (37 men, 15 women, mean 57 years), and acute myocardial infarction (52 men, 9 women, mean 58 years). In every subject, serum IgE measurement, eosinophil count, and stool examination for parasites were performed. Every subject was interviewed concerning history of allergy, smoking habits and the other risk factors for coronary arterial disease. In a model including the factors that may affect the serum levels of IgE (namely, age, sex, cigarette smoking, parasites, and family and personal history of allergy), IgE levels were found to be significantly higher in the patients with unstable angina and acute myocardial infarction compared to the patients with stable angina pectoris and controls. These data indicate that IgE may play a role in the pathogenesis of unstable angina pectoris and acute myocardial infarction. PMID- 1869330 TI - Prognostic significance of right ventricular ejection fraction following inferior myocardial infarction. AB - The prognostic significance of right ventricular ejection fraction, measured by radionuclide ventriculography, was assessed in 168 consecutive patients with inferior myocardial infarction. Right ventricular ejection fraction was 0.40 or less in 35 patients. Over a follow-up period of 40 months, there were 15 deaths in the total group of 168 patients, eight (23%) in the 35 with right ventricular ejection fraction of 0.40 or less, and seven (5%) in the remainder of the group. The one year survival of patients with right ventricular impairment (84 +/- 6%) was significantly worse (P less than 0.01) than those with a right ventricular ejection fraction over 0.40 (95 +/- 2%). A multivariate Cox model analysis showed age (P less than 0.001), left ventricular ejection fraction (P less than 0.01), and right ventricular ejection fraction (P less than 0.03) to be independent predictors of survival. Impaired right ventricular function is an adverse prognostic factor in patients with inferior infarction, particularly in those with impaired left ventricular function. PMID- 1869331 TI - Does Fourier phase shift correlate with conduction delay in bundle branch block? AB - Fourier analysis of radionuclide ventriculography is adept at qualitatively demonstrating interventricular conduction delay in bundle branch block. In this study of eighteen patients, there is a considerable individual variation when the phase delay is expressed as an absolute conduction delay (milliseconds). Much of this variability persists after curve representation by the Fourier function has been optimized. It is suggested that this variability is due to differences in the shape of the right and left ventricular time-activity curves, reflecting differences in contraction and relaxation in the two ventricles. Such differences may be more pronounced in some subjects than others. These results suggest that absolute conduction delay cannot be reliably achieved by this method. PMID- 1869332 TI - Value and limitations of transesophageal echocardiographic monitoring during percutaneous balloon mitral valvotomy. AB - To determine the utility of transesophageal echocardiographic monitoring during percutaneous balloon mitral valvotomy, we analyzed data from 40 consecutive patients who had been randomly assigned to undergo balloon mitral valvotomy under transesophageal echocardiographic guidance or without echo. All procedures were carried out under general anaesthesia. The completion rate (100% vs 73%), the procedure time (108 +/- 28 min vs 65 +/- 18 min), the X-ray exposure time (62 +/- 13 vs 33 +/- 12 min), resulted significantly (P less than 0.001) more favorable in the echo-monitored patients. Moreover, a lower rate of major complications (cardiac tamponade, large residual atrial shunting, and severe mitral regurgitation) was noted in the echo-monitored patients. The achieved final area of the mitral valve did not differ significantly between the two groups. From an evaluation of results as a whole, 96% of the echo-monitored procedures were successful, whereas only 40% of the procedures conducted without echocardiographic control achieved a satisfactory final result in absence of major complications. We conclude that transesophageal echocardiography is a safe, effective, and valuable tool to monitor each step of balloon mitral valvotomy in order to shorten the time of the procedure, and to improve the results of this complex interventional catheterization technique. PMID- 1869334 TI - Myocardial infarction with ventricular aneurysm in a newborn with normal coronary arteries. AB - Myocardial infarction is very rare in a neonate with structurally normal coronary arteries. We report a case in which myocardial infarction was complicated by a left ventricular aneurysm in the setting of normal coronary arteries. There was an associated muscular ventricular septal defect. All defects were diagnosed by cross-sectional echocardiography, angiography and myocardial scintigraphy. PMID- 1869333 TI - The effect of acute hypoxia on right ventricular function in healthy adults. AB - Right ventricular ejection fraction and right ventricular volumes were derived in 12 healthy male subjects using krypton-81m equilibrium radionuclide ventriculography whilst subjects breathed 30% (high inspired oxygen) and then 8 12% oxygen in nitrogen mixture (hypoxia). 'Physiological' tricuspid valve regurgitation was identified in 7 of the subjects by Doppler echocardiography, and right ventricular peak systolic pressure was estimated during high inspired oxygen and during hypoxia. Mean right ventricular peak systolic pressure was 24.1 +/- 3.3 mmHg during high inspired oxygen and increased to 41.3 +/- 8.4 mmHg during hypoxia (P less than 0.01). Mean right ventricular ejection fraction was 0.612 +/- 0.075 during high inspired oxygen and was unchanged at 0.590 +/- 0.073 during hypoxia. There was no significant change in right ventricular end diastolic volume or stroke volume in response to hypoxia. The systolic performance of the normal right ventricle is well-maintained during an acute rise in afterload induced by hypoxia. PMID- 1869335 TI - Aneurysm of the left sinus of Valsalva causing severe mitral regurgitation. AB - A 24-year-old male presented with exertional dyspnoea of one year's duration. Echocardiography revealed an unruptured aneurysm of the left sinus of Valsalva distorting the mitral valvar apparatus and producing severe regurgitation in the absence of myocardial ischemia or infarction. We propose an alternate mechanism for the mitral regurgitation. PMID- 1869336 TI - Mediastinal haematoma in Ehlers-Danlos syndrome. AB - A patient with Ehlers-Danlos syndrome presented acutely with clinical and radiological features suggestive of aortic dissection. Further investigations including computerised tomography and aortography showed mediastinal haematoma with no evidence of aortic dissection. He was treated conservatively with no complications. The typical clinical and radiological features are reviewed and an emphasis is made on accurate diagnosis to allow prompt, appropriate management. PMID- 1869337 TI - Aortopulmonary window with aortic origin of the right pulmonary artery. AB - Cross-sectional Doppler echocardiographic diagnosis of an aortopulmonary window with type B interrupted aortic arch, and anomalous origin of the right pulmonary artery from the ascending aorta was made in a 15-day-old neonate. This is the first known reported case of surgical repair for this rare association based on prospective echocardiographic diagnosis alone. PMID- 1869338 TI - Endocarditis due to Salmonella Dublinae. AB - We describe, to the best of our knowledge, the first reported case of endocarditis due to Salmonella Dublinae, which occurred in a patient with surgically corrected congenital heart disease. The diagnosis was established from positive blood cultures and echocardiography, and the patient was treated by intravenous antibiotic therapy with clinical success at six months follow up. The diagnosis and its implications for management are discussed, together with a review of previously reported cases of endocarditis caused by the Salmonella group of organisms. PMID- 1869339 TI - Simultaneous occurrence of the MB isoenzyme of creatine kinase and macro creatine kinase type 1 in a patient with acute myocardial infarction. AB - When the immunoinhibition method is used for differentiation of isoenzymes of creatine kinase, the simultaneous occurrence of the MB isoenzyme and variants of macro creatine kinase may lead to misinterpretation in the diagnosis of acute myocardial infarction. We describe the case of an elderly woman in whom the MB isoenzyme and the type 1 variant of macro creatine kinase were found simultaneously in her serum after acute myocardial infarction. It proved possible to identify the MB isoenzyme rapidly using a fast enzymeimmunoassay. PMID- 1869340 TI - Intra-myocardial haemorrhage following recanalisation of a venous coronary arterial bypass by balloon angioplasty. AB - We report the case of a patient presenting an intra-myocardial hematoma after recanalisation of a saphenous aorto-right coronary arterial bypass graft implanted 10 years previously after posterior myocardial infarction. The intra myocardial hematoma occurred immediately after recanalisation of the graft and was complicated by transient complete atrio-ventricular block. An acute increase of coronary capillary perfusion pressure may cause intramyocardial bleeding when capillary permeability is altered by prolonged ischemia or necrosis. In this case the resulting hematoma was limited to the segment of left ventricular wall affected by the previous necrosis and there was no further myocardial damage. PMID- 1869341 TI - An unusual form of horseshoe lung with hypoplasia of the right pulmonary artery. AB - The occurrence of horseshoe malformation of the lungs is very rare, especially in association with anomalies of the pulmonary arteries such as a pulmonary sling. We describe a case which, as far as we know, is the first example of this association. PMID- 1869342 TI - Pharmacokinetics of oral cefatrizine in patients with impaired renal function. AB - The pharmacokinetics of cefatrizine was studied in 15 patients with various degrees of renal impairment, after single oral administration of 500 mg. Cefatrizine elimination was reduced in parallel to renal function, as indicated by the significant correlations between apparent clearance (Cl/F) and creatinine clearance (Clcr), and between renal clearance (Clr) and creatinine clearance (Clcr). In patients with totally impaired renal function, the residual clearance (Cl/F) was 63 ml.min-1 per 1.73 m2. Comparisons with previously published data indicate that the apparent volume of distribution (V/F) of cefatrizine was lower in patients with impaired renal function than in young healthy volunteers, leading to increased peak concentrations (Cmax), but there was no relationship between V/F and Clcr. In patients with totally impaired renal function, the upper limit of cefatrizine elimination half-life was estimated to 5.5 h. The clinical significance of pharmacokinetic modifications observed in renal disease patients may only be realized through integration of pharmacodynamic characteristics of cefatrizine. The observed increase in Cmax and the lengthening of t1/2 could suggest a reduction of dosing frequency in patients with severe renal impairment. PMID- 1869343 TI - Antitussive effects of diphenhydramine on the citric acid aerosol-induced cough response in humans. AB - This controlled crossover study in twenty healthy volunteer subjects utilized the citric acid aerosol-induced cough response as a means to demonstrate the effectiveness of 25 mg of diphenhydramine as an antitussive. Entry was limited to only those subjects who manifested a consistent, quantitatively definable response to a 5% citric acid challenge. Subjects were initially dosed with either a placebo vehicle or 25 mg diphenhydramine in a 10 ml formulation. Following drug ingestion, subjects were challenged at 15, 30, 45, 60, 120, and 240 minutes. Three days later, subjects were administered the alternate treatment and rechallenged at the same time points. Diphenhydramine was effective at the earliest time point assessed, 15 minutes, and continued to be as effective over the entire 4-hour duration of the test period. For the placebo vehicle, the mean cough counts did not change significantly from baseline. Neither the putative soothing effect of a liquid formulation nor accommodation to the citric acid spray can account for all the early and consistently significant activity of diphenhydramine in suppressing the cough response. The early onset of activity of diphenhydramine may be due to its local anesthetic properties or may indicate that the dose of diphenhydramine required for effective antitussive activity is lower than that required for effective antihistaminic activity. These results require further corroboration in direct comparisons of various doses of diphenhydramine with positive controls in both this model and clinical cough counting models employing pathologic cough indices. A 25 mg dose of diphenhydramine appears to be effective as an antitussive agent. PMID- 1869344 TI - The influence of choline ascorbate on the blood levels of ascorbic acid in humans. AB - Our study has clearly shown that the oral administration of choline ascorbate, which contains approximately 500 mg of ascorbic acid to the volunteers causes an increase in the blood levels of ascorbic acid. This increase is statistically significant (p less than 0.01) compared with the basal level each time. In the control group, vitamin C tablet also causes an increase in the blood level of ascorbic acid. However, this increase is less than that of the test group. Our results indicate that ascorbic acid, as a part of choline ascorbate molecule, reaches the blood circulation without losing its activity. PMID- 1869345 TI - The importance of pharmacokinetic data on sulpiride: results of a bioequivalence study of two sulpiride 200 mg preparations following oral administration. AB - In a within-subject comparative trial in 16 healthy volunteers, the bioequivalence of two sulpiride 200 mg preparations was tested using a model-free method of calculation as well as assuming 2- and 3-compartment models. As to AUC act., AUC inf. and Cmax, the test preparation was shown to be significantly superior. Some other differences were found depending on which calculation method was used. The Cmax of the test preparation showed therapeutically relevant plasma concentrations of greater than 400 ng/ml, compared with about 300 ng/ml for the reference preparation. Based upon the raw data obtained, it was the aim of this study to gain further knowledge about other kinetic parameters on which only few data is available. T1/2 beta, clearance, volume of distribution and MRT were calculated using 2- and 3-compartment models. Comparisons with literature data were made and it resulted that a better description of the sulpiride kinetics was obtained when a 3-compartment model was used. Finally, the course of the plasma level was calculated by computer extrapolation assuming a thrice daily administration of sulpiride 200 mg. As a result, steady-state is reached after 3 4 days showing plasma concentrations around 650 ng (reference preparation) and 850 ng (test preparation). PMID- 1869346 TI - Blood binding of selezen (imidazole salicylate) in man. AB - The interactions of selezen (imidazole salicylate) with human blood components were studied by equilibrium dialysis. These interactions were limited to the binding of salicylate to human serum albumin (HSA). The binding was saturable and involved several classes of binding sites with different association constants. A competition study indicated that salicylic acid at high concentration was able to displace warfarin and digitoxin but not glibenclamide from their HSA sites. On the other hand, selezen serum binding was decreased in renal impaired patients and this result was probably linked to the decreases in HSA concentration. So the use of small dosage regimens of selezen to these patients can be proposed. The same recommendation may be done for cirrhotic patients, where the decrease of selezen binding percentage was observed and due to both hypoalbuminemia and hyperbilirubinemia. PMID- 1869348 TI - The Bancroft-Mackerras Medal of the Australian Society for Parasitology. PMID- 1869347 TI - Points in question. Genetic diversity in Echinococcus granulosus--a reply to McManus. PMID- 1869349 TI - Towards a synthetic Babesia vaccine. PMID- 1869350 TI - Parasitic zoonoses in perspective. PMID- 1869351 TI - Immunodiagnosis of angiostrongyliasis with monoclonal antibodies recognizing a circulating antigen of mol. wt 91,000 from Angiostrongylus cantonensis. AB - In the analysis of excretory-secretory (ES) antigens from infective third-stage larvae (L3) of Angiostrongylus cantonensis, one major component of mol.wt 91,000 was not precipitated by pooled sera of patients with eosinophilic meningoencephalitis. Monoclonal antibodies (Mc Ab) secreted from two hybridoma cell lines, established against somatic antigens of L3, recognized this molecule but with different epitope specificities indicated by an additivity index (A.I.) of 83%. The 2 Mc Ab (TD2 and 3A5) belonged to IgG2a and IgM classes, respectively. Combinations of TD2 and 3A5 were used in a sensitive enzyme-linked fluorescent assay (ELFA) for the immunodiagnosis of human angiostrongyliasis. The double-antibody sandwich ELFA method was applied firstly to sera from experimentally infected rats using either TD2 or 3A5 to coat the assay plates. Two fluorescence unit (F.U.) peaks appeared in sera from infected rats collected 18 and 44 days after infection. Specimens from 35 patients were tested, all cerebrospinal fluids (CSF) and most sera (88%) showed positive reactions and the average F.U. of CSF was greater than that of serum. PMID- 1869352 TI - The use of electroblotted antigens of Trichostrongylus colubriformis to induce proliferative responses in sensitized lymphocytes from sheep. AB - Merino sheep were immunized against the intestinal nematode, T. colubriformis, by repeated infections, and proliferative responses of their peripheral blood lymphocytes (PBL) against parasite extracts and excretory-secretory (ES) antigens were monitored over 130 days. Maximal responses occurred 7-14 days after challenge. The ability of soluble proteins and parasite antigens to induce proliferation was compared with that of antigen-bearing particles obtained after antigen was adsorbed onto nitrocellulose. Blank particles increased c.p.m. two- to three-fold above that obtained in medium alone, and to elicit proliferative responses of comparable magnitude between 10 and 100 times more antigen was required when antigen-bearing particles were used instead of soluble extracts or defined proteins. Blood leucocytes as well as T-cell lines established by stimulation with parasite antigens in vitro reacted to moieties of from 5000 to 38,000 mol. wt in ES antigens on nitrocellulose particles. Direct comparisons of T-lymphocyte responses with antibody responses as assessed by immunoblots revealed different profiles of immunogenicity among ES proteins within individual sheep, but the 10,000, 30,000 and 75,000-90,000 mol. wt proteins were immunodominant. These proteins were also those consistently recognized by T lymphocytes and sera from sheep immunized with ES proteins in adjuvant. Thus, this technique can be applied to identify parasite material which is immunogenic for T-lymphocytes, but the sensitivity of the procedure in sheep is less than reported in human studies. PMID- 1869353 TI - Host-parasite interface of the urinary bladder-inhabiting nematode Trichosomoides crassicauda: changes induced in the urothelium of infected rats. AB - The urinary bladders of rats infected with Trichosomoides crassicauda were studied by light, scanning and transmission electron microscopy. The bladder epithelium of infected rats showed a diffuse, mild, flat hyperplasia, four to six cells thick. The anterior parts of adult female worms were embedded in tunnels within the hyperplastic epithelium with the posterior portions of the parasites lying free in the bladder lumen. The hyperplastic epithelial cells forming the inner layer of the tunnel wall, adjacent to the parasite, showed degenerative changes. These cells contained single or multiple pycnotic nuclei. Their cytoplasm was fibro-granular in appearance, with few distinct organelles, and the luminal surfaces of the cells were not limited by plasma membranes. Small numbers of granular cells, similar in appearance to mast cells, were seen in, and possibly crossing, the epithelium. There was no infection-related increase in the number or type of inflammatory cells in the lamina propria. Questions of interest emerging from this study relate to the nutrition of an adult nematode occupying an intra-epithelial location, and the absence of a significant chronic inflammatory response to the mature worm. It is suggested that the avascular hyperplastic epithelium of the bladder is an immunologically 'protected site' for the mature female T. crassicauda. PMID- 1869354 TI - Genetic evidence for three species within Pseudoterranova decipiens (Nematoda, Ascaridida, Ascaridoidea) in the North Atlantic and Norwegian and Barents Seas. AB - Genetic variation of 1017 specimens of codworm, Pseudoterranova decipiens, collected from fish and seals at 23 sampling locations in the North Atlantic and Norwegian and Barents Seas, was analysed on the basis of 16 enzyme loci. Three reproductively isolated species, provisionally designated P. decipiens A, B and C, were detected, showing distinct alleles at the following loci: Mdh-1, 6Pgdh, Np, Pgm, Est-2 (between species A and B); Mdh-3, 6Pgdh, Np, Sod-1, Adk, Pgm, Est 2, Mpi (between A and C); Mdh-1, Mdh-3, Sod-1, Adk, Pgm, Est-2, Mpi (between B and C). One F1 hybrid was observed between P. decipiens A and B, but this apparently does not lead to any gene exchange between the two species, which do not show any evidence of introgression. No hybrids or introgressed individuals were observed between P. decipiens C and either A or B. Genetic distances among conspecific populations were low (average Nei's D 0.001-0.005), even though they were collected thousands of kilometres apart, indicating high levels of gene flow within each of the three species. The values of Nei's index D were 0.44 between P. decipiens A and B, 0.57 between B and C, and 0.79 between A and C. Estimated evolutionary divergence times, using Nei's formula, range from 2 to 4 million years. Differences between P. decipiens A, B and C were also found with respect to genetic variability, morphology, geographical distribution and hosts. Mean heterozygosity values of 0.08, 0.05 and 0.02 were obtained for P. decipiens A, B and C, respectively. Preliminary morphological examination of adult males, previously identified by multilocus electrophoresis, revealed differences in the relative size and pattern of caudal papillae. P. decipiens B is widespread in the study area, whereas P. decipiens A was found only in the North-East Atlantic and Norwegian Sea. In this area P. decipiens A is most common in the grey seal, Halichoerus grypus, while the common seal, Phoca vitulina, is the main host for P. decipiens B. In Canadian Atlantic waters, where P. decipiens A is apparently absent, P. decipiens B infects both grey and common seals; a few specimens were also found in the hooded seal, Cystophora cristata. The only definitive host so far identified for P. decipiens C is the bearded seal, Erignathus barbatus; P. decipiens C appears to be widespread, occurring in both the North-West Atlantic and Barents Sea. PMID- 1869355 TI - Lack of correlation between red cell invasion by merozoites and anti-heat shock protein-70 antibody levels in malaria patients' sera. AB - A total of 172 sera samples were collected from individuals who were living in Piyawli-Jaitwarpur village in Ghaziabad district (U.P.), India. They had suffered from falciparum malaria attack, and were cured with antimalarial drugs 1-2 weeks prior to sample collection. These samples were divided into nine groups according to their age. The pooled sera from each group were tested for the presence of anti-schizont and anti-heat shock protein (hsp)-70 antibodies, as well as for parasite growth inhibition in vitro. All sera samples showed significant levels of antibodies against schizont antigens and these levels increased with age. The sera also contained anti-hsp-70 antibodies but at lower levels and did not follow the same age-related pattern as seen with schizont antibodies. The sera from each group significantly inhibited merozoite invasion in vitro. However the same was not true for other blood stage parasites; the 2-15 years age group sera did not show significant growth inhibition of rings, trophozoites and schizonts. No correlation was observed between anti-hsp-70 antibody levels and inhibition of merozoite invasion. It is therefore concluded that the antibodies preventing the merozoite invasion could be other than anti-hsp-70 antibodies. The candidature of hsp-70 for P. falciparum malaria vaccine thus needs to be re-evaluated. PMID- 1869356 TI - Identification of a putative eggshell precursor protein of the female Schistosoma japonicum. AB - In adult worms of Schistosoma japonicum, a prominent radiolabelled female specific protein (34 kDa) was demonstrated on fluorography of SDS gels with the pulse incorporation of 14C-tyrosine in vitro, though it was difficult to detect major female-specific proteins by direct staining methods. This female-specific protein was demonstrated to localize exclusively in the vitelline cells by indirect immunofluorescence using the rabbit anti-34 kDa female protein antiserum. It was shown that 14C-tyrosine was selectively incorporated into the vitelline cells by the pulse labelled autoradiographs. Two days after the exposure of worms to radio-tyrosine, the shells of eggs in the uterus were demonstrated to have become radioactive, indicating that 14C-tyrosine-labelled protein was used as a material for the eggshell. In the fluorograph of proteins extracted from newly laid eggs in vitro, the prominent band was not found at the 34 kDa region, but a lot of radioactivity appeared at higher than 100 kDa. The results suggested that a 34 kDa female protein was a precursor of the eggshell and became a much larger protein molecule as a result of cross-linking during eggshell hardening. PMID- 1869357 TI - An established cell line of larval Echinococcus multilocularis. AB - A cell line of larval Echinococcus multilocularis has been established from an echinococcal cyst excised surgically from a patient with alveolar hydatid disease. A standardized procedure established for the preparation and continuation of primary cultures was applied to isolate the E. multilocularis cells from the tissue fragments. Trypsin was used for the enzymatic release of the monodispersed cells from the tissue fragments and for dispersing monolayers. The culture medium was RPMI 1640 with 10% fetal calf serum. Cell supports were collagen-coated plastic dishes and flasks. The morphological features of the cultured cells showed spindle-like cells during the first few subcultures, and then polygonal or star-like cells. Population doubling time at passage 34 was approximately 23 h and plating efficiency at the same passage was 15%. Chromosome numbers obtained from 70 metaphase plates at passage 40 ranged between 14 and 104 and cells with 91-100 chromosomes were clearly predominant. The chromosomes could be morphologically classified into telocentric, subtelocentric, and metacentric types. Over 90% of the chromosomes were of the telocentric type. Cells collected at passage 57 were intraperitoneally inoculated into two cotton rats (Sigmodon hispidus) at a cell concentration of 10(7) and the rats were sacrificed 100 days later. It was found that the two rats had echinococcal cyst masses in the peritoneal cavity. This result indicates that our isolated cells are germinal cells with ability to differentiate into cystic structures in vivo. PMID- 1869358 TI - Hymenolepis nana: immunity against oncosphere challenge in mice previously given viable or non-viable oncospheres of H. nana, H. diminuta, H. microstoma and Taenia taeniaeformis. AB - When mice, previously given oral inoculation with viable oncospheres of the heterologous cestode species (Hymenolepis diminuta, H. microstoma, Taenia taeniaeformis) and the homologous one (H. nana), were challenged with oncospheres of H. nana 4 days after the primary inoculation, they showed strong and complete resistance to H. nana challenge, respectively. However, the resistance was not evoked in mice given either infective eggs of Toxocara canis or non-viable oncospheres of all cestode species examined. Congenitally athymic nude mice given viable oncospheres did not show any resistance to H. nana either. Eosinophil infiltration around cysticercoids of H. nana in the intestinal villi appeared to be more prominent in mice previously given viable oncospheres of H. diminuta than in mice given non-viable oncospheres or PBS only. Some of the eosinophils in the villus harboring cysticercoid(s) of H. nana invaded the epithelia in the former, whereas all eosinophils remained in the lamina propria in the latter. There was almost no eosinophil infiltration in nude mice. Microscopic observations revealed that oncospheres of H. diminuta, which require beetles as the intermediate host like H. microstoma, could invade the mouse intestinal tissue. Therefore, it is strongly suggested that the strong cross resistance to H. nana in mice, induced by oncospheres of all heterologous cestode species, is thymus-dependent and due to oncospheral invasion into the intestinal tissue of mice. PMID- 1869359 TI - The distribution of lice (Phthiraptera) on poultry (Gallus domesticus). AB - The distribution of three amblyceran (Menacanthus stramineus, Menacanthus cornutus, Menopon gallinae) and five ischnoceran species (Lipeurus lawrensis tropicalis, Lipeurus caponis. Goniocotes gallinae, Goniodes gigas, Goniodes dissimilis) on poultry was determined. The preferred sites of these species on the host body were recorded. PMID- 1869360 TI - Antibody responses against natural Taenia hydatigena infection in dogs in Kenya. AB - Antibody responses (IgG) against Taenia hydatigena infection in dogs in Kenya were analysed in ELISA using excretory/secretory products of T. hydatigena scoleces derived from goat cysticercus cysts. Helminth infections of individual dogs were confirmed at autopsy. T. hydatigena worms were found in 89.5% of 143 dogs, and positive anti-T. hydatigena antibody levels were detected in 58.7% of infected dogs. Positive antiscolex antibody levels were detected in 40.0% of Turkana dogs uninfected with T. hydatigena, suggesting previous infection. Antibody was not detected in 34.4% of infected dogs. There was no relationship between individual T. hydatigena worm burdens and absorbance values for sera in ELISA. It was not possible to distinguish between sera from T. hydatigena infected and uninfected dogs. PMID- 1869361 TI - The expulsion of Echinostoma trivolvis and retention of Echinostoma caproni in the ICR mouse: pathological effects. AB - The infectivity and distribution of Echinostoma trivolvis were studied in female ICR mice each infected with 25 metacercarial cysts. At 7 and 10 days post exposure worm recoveries were 58.8 and 58.4%, respectively. Worm recovery declined to 38.2% by day 14, to 6.4% by day 21, and 0% by day 28. The distribution of the parasites demonstrated an anteriad shift over time. Comparative histopathological studies were carried out on E. trivolvis and Echinostoma caproni in the mouse. Compared to control and E. trivolvis-infected intestine, mouse intestine infected with E. caproni showed marked dilation and villous atrophy. E. trivolvis-infected intestine showed a nearly two-fold increase in goblet cells compared to control intestine, whereas the intestine of E. caproni-infected mice showed almost complete goblet cell loss. Additionally, there was a marked increase in collagen in the intestinal musculature of the mice infected with E. trivolvis compared to control and E. caproni-infected mice. PMID- 1869363 TI - Tick resistance in mast cell-deficient mice: histological studies. AB - Mast cell-deficient W/Wv mice and their mast cell-sufficient +/+ genetic controls were allowed to undergo three successive infestations with Dermacentor variabilis larvae. Histological examination of the skin of infected mice revealed large dermal accumulations of eosinophils and smaller numbers of neutrophils. The numbers of both eosinophils and neutrophils increased significantly in W/Wv and +/+ mice during secondary and tertiary infestations. Mast cell numbers were also found to increase in the skin of +/+ mice during tertiary infestations. Resistance, as measured by decreased larval engorged weights on day 5 of each infestation, was acquired by both strains of mice. PMID- 1869362 TI - The life cycle of Echinochasmus bagulai (Trematoda: Echinostomatidae). AB - The life history of Echinochasmus bagulai, an echinostomatid trematode in birds, is reported and stages in the life cycle are described. Natural infections with cercariae, which are of the gymnocephalous type, were found in the thiarid snail Thiara tuberculata. Metacercarial cysts were found in the gills of Aplocheilus panchax, Oryzias melastigma, Gambusia affinis and Channa punctata. Adults were obtained in the small intestine of Ardeola grayi. In laboratory experiements development of cercariae into infective metacercariae took 10 days in the gills of A. panchax. Mature flukes were recovered in 10 days in the small intestine of experimentally infected 1-day-old leghorn chicks. The eggs collected from the faeces of these infected chicks were incubated at 39 degrees C. The free-swimming miracidia were found on the fifth day of incubation. PMID- 1869364 TI - Poor efficacy of albendazole for the treatment of human taeniasis. AB - In order to evaluate the efficacy of albendazole for the treatment of taeniasis, regimens of 400 mg x 1 day, 800 mg x 2 days, 800 mg x 3 days, 1200 mg x 2 days, and 1200 mg x 3 days were compared. Of 66 cases treated and investigated 7-14 days after treatment, 52 were still expelling proglottids. Three months posttreatment, these cases were re-treated with atabrine at 1.2 g per case for males and 1.0 g per case for females. Fifty-seven patients expelled worms or parts of tapeworms. The nine negatives may represent the number cured by the treatment with albendazole. The cure rates with albendazole for various regimens were up to 50% for 800 mg x 3 days, 1200 mg x 2 days or 1200 mg x 3 days, 14.3% for 800 mg x 2 days, and 0% for 400 mg x 1 day or 800 mg x 1 day. This study shows that albendazole is not very effective in the treatment for taeniasis. PMID- 1869365 TI - Relationships between clinical protection and antibodies to Plasmodium falciparum RESA (ring-infected erythrocyte surface antigen) peptides. AB - A longitudinal study involving 76 individuals living in Dafinso and Vallee du Kou (near Bobo-Dioulasso, Burkina Faso, West Africa) was performed in June 1987 (beginning of the transmission period), August-September 1987 (during) and January 1988 (after). The serological antibody (Ab) responses against synthetic peptides representing repeat amino acid sequences of the P. falciparum Ring Infected Erythrocyte Surface Antigen (RESA): (EENV)5, (EENVEHDA)4, (DDEHVEEPTVA)2 were evaluated by ELISA. The clinical longitudinal study during the transmission period allowed us to define three different groups in terms of age and occurrence of clinical malarial attack (greater than 5000 parasites mm-3 of blood and axillary fever greater than 37.7 degrees C). Levels (A620) of Ab to (EENVEHDA)4 and (DDEHVEEPTVA)2 were correlated with age. The adult group (III) had the highest prevalences of Ab to RESA peptides. No significant difference was found between groups of children with or without malaria attack. Nevertheless, at the beginning of the transmission period, children who had at least one malaria attack during the study presented the lowest level of antibodies to RESA peptides. PMID- 1869366 TI - Characteristics of a leucine aminoacyl transfer RNA synthetase from Tritrichomonas augusta. AB - This study has investigated the characteristics of a leucine aminoacyl transfer RNA synthetase enzyme from Tritrichomonas augusta. Differential centrifugation and DEAE-cellulose column chromatography were used for partial enzyme purification. The column purification increased the synthetase activity 125-fold over the unfractionated cell extract. The conditions for maximum [3H] leucine charging were 37 degrees C for 20 min, with protein at 180 micrograms ml-1 using yeast leucine tRNA as an acceptor. The optimal reaction conditions were 14 mM-Mg acetate, 3 mM-ATP, 3 mM-spermidine and 5.5 mM-putrescine. Acceptor activity with T. augusta transfer RNA was 8-fold higher than with yeast transfer RNA and 25 fold higher than with Escherichia coli transfer RNA. The partially purified enzyme fraction had comparable changing activities for both leucine and valine. PMID- 1869367 TI - Glyco-tuftsin derivatives modulate interleukin-1 and tumor necrosis factor production. AB - Six Thr1 (O-glyco)-derivatives of the "phagocytosis stimulating peptide" tuftsin, H-Thr-Lys-Pro-Arg-OH and the N-glycosylated undecapeptide H-Thr-Lys-Pro-Arg-Glu Gln-Gln-Tyr-Asn(beta-D-GlcNAc)-Ser-Thr-OH, which correspond to the "tuftsin region" at the Fc-domain of immunoglobulin G (amino acid residues 289-299), were evaluated in comparison with tuftsin and rigin, H-Gly-Gln-Pro-Arg-OH, for their capacity to evoke the release of interleukin-1 and tumor necrosis factor from mouse peritoneal macrophages and from human monocytes. Several glycosylated tuftsin derivatives were found to modulate, in a rather dose-dependent manner, the release of the two cytokines from both cell types. PMID- 1869368 TI - Structure and conformation of peptides containing the sulphonamide junction. III. Synthesis, crystal and molecular structure of a taurine containing peptidic oxa cyclol. AB - The insertion of the (S)-lactyl residue into the cyclodipeptide cyclo (-Tau-Pro-) 3 leads in good yields to the first example of a stable tetrahedral adduct (oxa cyclol) 5 containing the sulphonamide junction. Compound 5 does not show a significant tendency towards tautomeric equilibria and possesses an unexpected syn-orientation involving the hydroxyl group and the Pro-H alpha. The crystal structure and molecular conformation of 5 has been determined. Crystals are orthorhombic, s.g. P2(1)2(1)2(1), with a = 6.607, b = 12.297, c = 16.622 A. The cisoidal conformation around the S-N bond is very similar to that found in the previously studied linear and cyclic peptides containing a sulphonamide junction. The taurine nitrogen is practically planar whereas the proline nitrogen, bound to the SO2 group, is highly pyramidal. In the tricyclic system of 5 the seven membered ring adopts a twist-chair conformation while the pyrrolidine and oxazolidinone rings show an envelope conformation. The crystal packing is characterized by three hydrogen bonds all formed by means of a water molecule. PMID- 1869369 TI - Solution conformation of endothelin-1 by 1H NMR, CD, and molecular modeling. AB - The solution conformation of Endothelin-1, a recently discovered bicyclic, 21 amino acid peptide, has been examined by 1H NMR in deuterated dimethylsulphoxide and circular dichroism in aqueous and organic solvents. A total of 158 NOEs were detected, which were used as distance constraints in the distance geometry program DISGEO. Two families of structures were obtained, both characterized by a helix-like region extending from Lys9 to Cys15, but with opposite "handedness". Circular dichroism studies of the peptide in both aqueous and trifluoroethanol solutions show a negative shoulder at 224 nm, characteristic of right-handed helices. Molecular dynamics and energy minimization yielded a solution structure for this new peptide compatible with all experimental observations. PMID- 1869370 TI - Conformational mimicry. II. An obligatory cis amide bond in a small linear peptide. AB - The structure of Z-Pro psi [CN4]-Ala-OBzl has been determined by X-ray crystallographic techniques. The structure crystallizes in space group P2(1) with cell constants a = 22.176(3) A, b = 6.141(1)A, c = 8.275(1) A, beta = 98.31(1), and Z = 2. The structure has been refined to a residual of 0.038 for 2538 independent data. The amide bond between the prolyl and alanyl residues is cis, a result of the presence of the tetrazole ring system, as is the urethane bond linking the benzyloxycarbonyl and the prolyl groups. A comparison of the structures in this study to other structures containing cis amide bonds shows that the tetrazole ring system, when incorporated into peptides, mimics a cis amide bond. Changes in the distance between the alpha-carbons adjacent to the tetrazole rings in the linear peptide as compared with the bicyclic diketopiperazine required a reassessment of the conformational mimicry with the cis amide bond. PMID- 1869371 TI - Biologically active conformations of thymopentin. Studies with conformationally restricted analogs. AB - Four cyclic analogs of thymopentin were synthesized and evaluated for biological activity on the human T cell line CEM. Three of these conformationally restricted analogs were biologically active. The one analog which most closely mimicked the conformation predicted from NMR and theoretical energy minimization calculations proved to be inactive. These studies establish that the biologically active conformations of thymopentin differ from the most probable conformation predicted from solution NMR and theoretical energy minimization studies. PMID- 1869372 TI - Conformational change that accompanies pepsinogen activation observed in real time by fluorescence energy transfer. AB - Pig pepsinogen has been reacted with N-carboxymethylisatoic anhydride to form N carboxymethyl-anthraniloyl-(CMA-) pepsinogen, derivatized at Lysp18, Lysp23, Lysp27, Lysp30, and Lys320. Conformational change associated with activation was detected by following energy transfer from tryptophan residues of the pepsin moiety, excited at 295 nm, to CMA groups, monitored by emission above 415 nm. Efficiency of this energy transfer is a measure of conformational change. For this zymogen derivative the change in efficiency occurs with a first order rate constant of 0.041 s-1 at pH 2.4, 22 degrees, which equals the rate at which, following acidification, alkali-stable potential activity becomes alkali-labile. For the native zymogen the rate of this conversion had been shown to be identical to the rate of cleavage of the scissile bond of pepsinogen. Therefore, the correspondence in this derivative of the rates of conversion to alkali lability and change in energy transfer demonstrates that a conformational change accompanies the peptide bond cleavage of activation. PMID- 1869373 TI - What is an 'otitis-prone' child? AB - The present report concerns a random sample of 2512 children monitored for acute otitis media up to the age of two years. The criteria given by previous surveys classified from 1.8 to 41.2% of the population as 'otitis-prone', at a mean age varying between 13.4 and 18.8 months. A criterion of at least 4 episodes of acute otitis media during the next 9 months with a 30-day borderline between two distinct episodes yielded 273 children (10.8% of the population) with an acceptable mean age of 15 months. Early onset of acute otitis media was only a weak predictor of susceptibility in either the individual child or the whole population, the sensitivity levels and predictive values being too low for accurate prediction. PMID- 1869374 TI - Radial versus circumferential incision in myringotomy and tube placement. AB - Pressure equalization tubes are a well-recognized treatment for persistent otitis media with effusion and recurrent acute otitis media. Ideally, the tube should remain in place until the Eustachian tube function returns. Efforts to improve the functional life expectancy of tubes have concentrated on tube design with little attention directed at modification of the surgical technique. Some authors have noted that a radial incision offers theoretical advantages over a circumferential incision. A randomized study comparing radial and circumferential incisions in myringotomy with tube placement was conducted. Two hundred and twenty-eight patients had a circumferential incision performed in one ear and a radial incision in the opposite ear. On follow-up examinations the tube position and time to extrusion were noted. Using the sign test, there was no statistical difference in extrusion rates between the two groups. This study does not support the theoretical advantages espoused in the literature. PMID- 1869375 TI - Surgery for congenital stapes ankylosis with an associated congenital ossicular chain anomaly. AB - The surgical findings and results are presented on 32 ears with congenital stapes ankylosis with an associated congenital anomaly of the ossicular chain. One third of the patients had a syndromal diagnosis. In 26 ears, stapedectomy could be performed. In 2 other ears, stapes ankylosis to the bony facial canal was mobilized successfully. In the 4 remaining ears, surgical intervention had to be limited to an exploratory tympanotomy for various reasons. The average hearing gain was 23 dB for the 28 ears on which stapes surgery had been performed. A substantial hearing gain of at least 15 dB was achieved in 19 of these 28 ears (68%). The end result was limited to a small extent by an average preoperative sensorineural component of 16 dB in the hearing loss. A review of the findings and results from other larger series in the literature are presented. PMID- 1869376 TI - Tympanoplasty surgery at the Red Cross War Memorial Children's Hospital 1986 1988. AB - Results of tympanoplasty surgery over a 3 year period in 96 children aged 2-12 years were analysed to better define indications for surgery and prognostic factors. Nineteen percent had a hearing loss associated with a dry perforation- grafts were successful in 84% and 71% improved hearing to less than 20 dB. Forty two percent had a hearing loss but also troublesome recurrent infection--grafts were successful in 88% but only 65% improved hearing to less than 20 dB. Thirteen percent had troublesome recurrent infection--grafts were successful in 79%. Twenty-two percent had uncontrolled infection, a cortical mastoidectomy together with myringoplasty produced a 75% take rate. Graft take was not affected by age, type of surgery, infection status or perforation size. Poor nutritional status and postoperative infection both had negative tendencies. In this small series there was a 10% re-perforation rate. PMID- 1869377 TI - Evoked otoacoustic emissions in infant hearing screening. AB - The main application of the ILO88 otodynamic otoacoustic analyser is clearly in detecting whether the peripheral auditory system is normal or pathological. The evoked otoacoustic emission technique in normal and hearing-impaired children for which audiometric data were known (n = 422 ears) was first performed. The correlation was excellent. The actual experimental group (n = 258 ears) consisted of children who are difficult to test with the conventional screening methods in school health services. The use of evoked otoacoustic emissions as screening instrument is new, and therefore several minimal practical criteria, advantages and limitations were defined. The evoked otoacoustic emission test tool is especially applicable in difficult to test children using conventional screening methods. PMID- 1869378 TI - Branchial anomaly in a newborn presenting as stridor. AB - A male patient presented at day 3 of life with a small anterior neck mass and mild intermittent upper airway obstruction. Despite intravenous antibiotics, the patient rapidly progressed to impending airway obstruction requiring surgical intervention. The clinical, radiographic, and histologic findings of this extremely rare case of a third branchial anomaly will be presented. The embryologic basis for the connection to the aerodigestive tract and the access provided to gram negative enteric organisms in newborns will be discussed. PMID- 1869379 TI - Acyclovir in the treatment of laryngeal papillomatosis. AB - We report the results obtained in a study of 3 young patients with laryngeal papillomatosis, who were treated with acyclovir after tumor excision using forceps was performed under microlaryngoscopy. No recurrence of the papillomatosis occurred between 18 and 42 months post-therapy. Laryngeal papillomatosis is the most common proliferative laryngeal lesion in children. Different non-surgical therapies have been used to prevent its recurrence but with poor results. Acyclovir is a drug with proved efficacy in DNA viral diseases. Since papillomata of the larynx is most likely a viral disease which is imputed to have a DNA virus etiology, acyclovir may be effective to control it. PMID- 1869380 TI - Airway compromise from nasal obstruction in neonates and infants. PMID- 1869381 TI - 10 cases of subperiosteal orbital abscess diagnosed by CT scan. PMID- 1869382 TI - Suction lipectomy preceding pregnancy and postpartum results. AB - A retrospective case-control study was undertaken to determine if women who have undergone suction lipectomy of the abdomen, flanks and lower extremities suffer any reversal of the beneficial results of the procedure as a result of a subsequent term pregnancy and parturition. Cases with two women subjects who became pregnant and experienced full-term pregnancies and healthy childbirth shortly following suction lipectomy of the torso and lower extremities are reviewed. Bodily measurements about significant planes were recorded prior to suction lipectomy, between suction lipectomy and pregnancy, and 32 weeks postpartum. Controls included three women patients who did not become pregnant following the surgery, for whom similar measurements were available pre-suction lipectomy and post-suction lipectomy at short-term and long-term follow-up. The hiatus between follow-ups allowed for a potential gestational period to match the two cases. Results showed insignificant, if any, change between measurements before and after pregnancy in cases; in controls, excellent agreement was also achieved between measurements taken post-surgically at short-term and at long term follow-up. Assuming normal gravid weight gain and maintenance of proper diet following pregnancy, measurements achieved by suction lipectomy are unaffected by pregnancy and parturition. PMID- 1869383 TI - Emergency obstetric hysterectomy in eastern Nigeria. AB - This study was undertaken to determine the incidence of morbidity and mortality of emergency obstetric hysterectomy at the University of Nigeria Teaching Hospital, Enugu, and also the modalities for reducing these complications. Of the 84 cases of emergency obstetric hysterectomy carried out at the Teaching Hospital between January 1979 and December 1988, 43 had antenatal care at the Teaching Hospital while the remaining 41 were referred cases. Sixty patients were operated upon for ruptured uterus while the remaining 24 were as a result of post partum causes such as uterine atony, adherent placenta, lacerated cervix and sepsis. The leading post-operative complications were fever, haemorrhagic shock and sepsis. A maternal mortality rate of 29.8% was recorded, with the referred patients contributing 68% of the mortality. Better supervision of antenatal care in the community studied, improved blood transfusion facilities in the Teaching Hospital and adequate prophylaxis with antibiotics are recommended to reduce morbidity and mortality in operated cases. PMID- 1869384 TI - Arterial microanastomosis technique by using only one stitch. AB - The starting point of this work is the description of a microsurgical technique designed to carry out termino-terminal arterial anastomosis in rats. The technique is based on the intussusception of the afferent vessel of the anastomosis in the efferent vessel, both of which are fixed by a horizontal U shaped stitch. Of the twelve cases which make up this series, haemorrhage appeared in two, and a postanastomotic aneurysm developed in one. The lack of complications both before and after operating, even in the long term, in the balance of the cases (75%), together with the simple and quick procedure of this kind of anastomosis, makes this technique a possible alternative to the classical techniques of vascular microanastomosis in experimental surgery. PMID- 1869385 TI - Management of abdominal contusion in polytraumatized children. AB - Management of abdominal contusion in polytraumatized children is based on the conservative treatment of spleen and liver lesions when it is possible. Ultrasonography and CTScan can give a good evaluation of splenic, liver, pancreas or kidney lesions. In some cases, if the haemodynamic conditions are good, a non operative treatment may be proposed. We report our experience of conservative management of intra abdominal lesions in children, about 91 cases in ten years. PMID- 1869386 TI - Colonic involvement in pancreatitis. Six cases more. AB - Lesions of the colon are generally considered to be sequelae of pancreatitis. They include: localized paralytic ileus (colon cutoff sign), necrosis, fistulae, stenosis and varices. On the basis of an extensive review of the literature (332 cases), it is suggested that the real incidence of these lesions is significant. The anatomic relationship of the large bowel to the pancreas is an important factor in the genesis and localization of the lesions. Enzymatic-inflammatory and ischemic processes are involved in the most highly supported theories. Each complication shows different diagnostic and clinical patterns. In this paper, six cases of such lesions are presented, including 2 cases of necrosis, 2 of stenosis, 1 of fistula and 1 case of localized paralytic ileus. PMID- 1869387 TI - Prophylactic use of a single dose of tobramycin in elective colorectal surgery. AB - The aim of this prospective study is to acquire clinical experience with a single high dose of tobramycin in prophylactic use. Sixty three patients undergoing elective colorectal surgery, were assigned to receive antibiotic prophylaxis (24 hours perioperatively) in the form of a single high dose of tobramycin and a classically recommended thrice-a-day (TID) administration of clindamycin. The planned dose for tobramycin was 3.3 mg/kg/day. Adjustment was made in case of impaired renal function. Serum levels of the drug were monitored. The results showed well predictable levels. Six out of fifty five evaluable patients (10.9%) presented postoperative infectious complications within the follow up period. No renal nor otovestibular toxicity was recorded. PMID- 1869389 TI - The fatal inevitability of groin hernias recurrences. PMID- 1869388 TI - Antibiotic prophylaxis for biliary tract surgery: selection of patient and agent. AB - One hundred and three patients undergoing biliary surgery have been entered in a randomized prospective trial for antibiotic prophylaxis. Fifty six received piperacillin (2 gr) and 47 tobramycin (100 mg). Cultures were taken from bile at operation and a clinical and microbiological assessment for infection was carried out postoperatively. Overall infection rate was significantly lower in the piperacillin group (P less than 0.05). The positive bile culture and wound infection rates were also lower in the piperacillin group, though this did not reach statistical significance. Anaerobic bacteria (three patients) and Streptococcus faecalis (one patient) were isolated in the tobramycin group. Overall postoperative infection rate was similar in patients with risk factors for infection and in those without. In conclusion, piperacillin did not significantly improve bile and wound infection rates compared to tobramycin. However piperacillin showed a more appropriate spectrum of activity. Antibiotic prophylaxis is suggested for all patients undergoing biliary surgery. PMID- 1869390 TI - Arterial reperfusion in human orthotopic liver transplantation by anastomosis of the celiac trunk to the right or left hepatic artery of the recipient. AB - Fifteen orthotopic liver transplants were performed from 23 April 1986 to June 1987 in 14 patients (age range 3-56 years). In 12 transplants, extracorporeal bypass was used. The installation was effected by suprahepatic and infrahepatic cava-caval and portaportal anastomoses. Arterial anastomosis was realized after reperfusing the graft through the vena porta. In 13 transplants the donor celiac trunk was anastomosed to the receptor's right hepatic artery. In one ten year-old girl, the donor celiac trunk was anastomosed to the left hepatic artery. In one patient who underwent retransplantation for rejection, the donor organ had two separate hepatic arteries and the right and left hepatic arteries were respectively anastomosed to the right and primitive hepatic arteries of the receptor. All patients were followed up periodically by Doppler echography and trimethyl-Br IDA 99 mTc scan, which, consistently confirmed the permeability of the anastomosis and dependent vessels, and the good perfusion and function of the grafts, which were free of infarcted areas. Three patients died at 30 and 31 days and postmortem studies demonstrated vascular permeability. Angiography was performed in one patient, evidencing a good vascular caliber in the hepatic arteriography. PMID- 1869391 TI - Endoscopic papillotomy under ultra-sonographic control. AB - A new endoscopic method for performing endoscopic sphincterotomy is described. Only after correct positioning of the papillotomy device has been ascertained can papillotomy be carried out. We have used ultra-sonographic examination to confirm the correct placement of the papillotomy device. This technique was first employed on a pregnant patient in 6-13-1988. After that we performed this procedure in another twelve patients. We believe it is an easy procedure and perhaps may be used for all patients with common bile duct stones of less than 1.2 cm of diameter without other bilio-pancreatic pathological condition. PMID- 1869393 TI - Amoebic liver abscess. Review of 220 cases. AB - Two hundred and twenty cases of amoebic liver abscess were seen between 1981 1986. The majority were young or middle aged males belonging to the lower socio economic group and 85% gave a history of drinking toddy (fermented palm juice). The highest incidence of the disease occurred during the peak toddy season (April to July). Toddy drinkers become susceptible perhaps because of the large dose of Entamoeba histolytica and bacteria ingested with the drink, associated malnutrition, poor hygiene, hepatic dysfunction and possible suppression of amoebistatic substance. Useful investigations consisted of skiagram and ultrasonography, the later being sometimes used to guide the aspiration needle to abscesses situated at unconventional sites. Over 88 per cent responded well to conservative treatment with aspiration(s). Laparotomy was required in slightly over 10% of cases and in these the mortality was 12% as compared to 2% with conservative treatment. Although a large amount of liver tissue appears to be destroyed, the residual liver damage is clinically, biochemically, macroscopically and microscopically minimal. PMID- 1869392 TI - Wound infection following biliary surgery. A prospective surgery. AB - Biliary surgery in general, with cholecystectomy in particular, is probably the commonest major elective abdominal operation worldwide. A prospective study has been completed on 141 biliary operations in which intra-operative bile swabs were taken, and other risk factors for wound infection sought. Patients' characteristics were: males 51, females 90 (1:1.8); mean age 42.4 +/- 16 years; mean Quetelet index for adults was 32 +/- 5. The operations were: emergencies 10, simple-cholecystectomies 112, and choledochotomies (including other concomitant procedures) 29. The observed wound infection rates were: overall 7.8%, simple cholecystectomy 3.6% and choledochotomies 24.1%, figures which agree closely with the national and international literature. The infected patients consumed, on average, 7 days more in hospital than the uninfected ones. We found three major risk factors for wound infection: patients aged 40 years or older (over 4-fold), choledochotomy (over 6-fold), and microbiologically proven wound co-ntamination (9-fold). We conclude that, given the consistently low (less than 4%), incidence of wound infection following simple cholecystectomy, routine antibiotic prophylaxis in this subset is probably unjustified. PMID- 1869394 TI - Subdiaphragmatic abscesses: myths and realities. A report on sixty-two cases. AB - The main cause (60.8%) of subdiaphragmatic abscesses in a series of 62 patients (of which 46 were males), was found to be hepatobiliary in nature. Radiology proved to be helpful in correct diagnosis (61%), as did ultrasonography (60%). Right sided subdiaphragmatic abscesses were (55/62) 88.7% of the total. Mean abscess volume was 500 ml while culturing efforts were in vain in 32% of the abscess cases (able to be cultured). The incidence of morbidity was (12/62) 19.4% and mortality (3/62) 4.8% in this series, where the treatment was solely through surgical drainage. Though closed drainage using ultrasonic guidance has been popular in the past decade, it has its drawbacks. Open surgical drainage therefore, as a well established mode of treatment, is recommended. PMID- 1869395 TI - Interposition of the first jejunal loop for reconstruction after total gastrectomy. AB - A new technique of reconstruction after total gastrectomy by interposing the first jejunal loop between the esophagus and the duodenum, is described. Vascular and neural integrity of the interposed intestinal segment is "guaranteed", resulting in acceptable muscular activity on intestinal contents and partial digestive function, with limited post-operative complications. The interposed jejunal loop assumes reservoir function and permits almost normal eating habits. Application of this technique to 18 patients undergoing total gastrectomy has resulted in a more than satisfactory post-operative functional and nutritional status over a one to 14 year follow-up period. PMID- 1869396 TI - Surgical treatment of bronchial carcinoid tumours. Radical surgery-prognosis. AB - 111 patients (59 male and 52 female) operated on for bronchial carcinoid are reviewed. Their average age was 48 years. 21 bronchoplastic procedures and 16 wedge-resections were performed. All of these patients are alive and no recurrences have been observed. In our experience the usual oncological criteria fail to give unanimous information for prognosis. Conservative resections such as bronchoplastic procedures and wedge- or segmental resections are to be encouraged under strict conditions because of excellent results. The 5-year survival of 52 resected patients amounted to 94.2%. PMID- 1869397 TI - [Hyperlipidemias]. PMID- 1869398 TI - [Active and passive prevention of viral hepatitis]. PMID- 1869399 TI - [Diagnosis and therapy of fulminant liver failure]. PMID- 1869400 TI - [Severe liver complications in protoporphyria]. PMID- 1869401 TI - [Gallbladder calculi: internal medicine and surgical alternatives of therapy]. PMID- 1869402 TI - Intraocular pressure-dependent and -independent phases of growth of the embryonic chick eye and cornea. AB - The pattern and relative rates of diametric growth of the avian eye and cornea are described throughout embryonic development. The effect of reduced intraocular pressure on eye and corneal diametric growth also was investigated. Between embryonic day 4 (E4) and 1 day posthatching, the eye undergoes two distinct phases of linear growth. The first phase (E4-10) is very rapid (1.193 mm/day). The second phase, after E10, is significantly slower (0.346 mm/day). By contrast, over the same developmental period, the cornea undergoes three distinct and sequential phases of linear growth. The second phase of corneal growth (E7-10) is the most rapid (0.429 mm/day) and separates two periods of slow growth (0.211 mm/day during E4-7 and 0.128 mm/day after E10). After the sustained release of intraocular pressure by intubation on E4, growth of both the eye and cornea is reduced significantly. Operated eyes grow at a rate of 0.356 mm/day (E4-10) and 0.155 mm/day (E10-16). Intubation reduces corneal growth to a single phase of 0.125 mm/day (E7-16). Thus, from E4-10 both the eye and cornea possess intrinsic growth potentials that are elevated significantly by intraocular pressure. After E10, the rate of growth of both the eye and the cornea is independent of intraocular pressure. Because both control and intubated eyes change their growth rate on E10, this transition also is independent of intraocular pressure. This contrasts with the cornea which, after intubation, shows no detectable variation in growth rate. Correlation of eye with corneal growth demonstrates an exponential relationship in the presence of intraocular pressure and an almost linear relationship after intubation. PMID- 1869403 TI - Infrared laser sclerostomies. AB - Four solid-state lasers with three fiberoptic delivery systems were used to perform laser sclerostomies in an acute-injury rabbit model and in fresh human globes. The lasers used were continuous-wave neodymium:yttrium aluminum garnet (YAG, 1.06 microns) and pulsed holmium:yttrium scandium galliam garnet (YSGG) (2.10 microns), erbium:YSGG (2.79 microns), and erbium:YAG (2.94 microns). Thermal damage to tissue and total laser energy required to produce sclerostomies decreased with increasing wavelength. In human tissue using a 600-microns fused silica fiberoptic, maximum thermal damage (greater than or equal to 100 microns) was noted at 1.06 microns with a total energy of 21 J at a power density of 2.5 kW/cm2. In addition, focal damage to the iris and ciliary body was noted at this wavelength. The least amount of thermal damage (15-20 microns) and lowest total energies needed were found at 2.94 microns. A 250-microseconds pulse length and pulse radiant exposures of 3.6 J/cm2 and 14.3 J/cm2 were used for the low hydroxyl-fused silica (500 microns) and zirconium fluoride (250 microns) fiberoptics, respectively. Although zirconium fluoride fibers have high through put efficiencies that facilitate study of laser tissue interactions at 2.94 microns, problems encountered with fragility and solubility of the bare tip in aqueous media limit its usefulness. A high attenuation rate with the low hydroxyl fused silica fiber limited its usable length to 35 cm at 2.94 microns. Tissue damage during sclerostomy formation was minimized at 2.94 microns, reaching a maximum at 1.06 microns. Minimizing tissue damage theoretically could decrease subconjunctival scarring and filtration failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869404 TI - The nocturnal suppression of aqueous humor flow in humans is not blocked by bright light. AB - Normal human subjects were studied hourly by fluorophotometry to measure the normal circadian rhythm of aqueous humor flow. On a separate day, the subjects slept for approximately 1 hr after lunch; this short nap was not found to have any effect on aqueous flow. On a separate night, the subjects slept under a bright light of 2500 lux; the light was not found to have any effect on flow in the sleeping subjects. Because bright light blocks melatonin release in humans, nocturnal suppression of aqueous flow in humans may not be driven by systemic melatonin release. PMID- 1869405 TI - Effect of chronic epinephrine on aqueous humor flow during the day and during sleep in normal healthy subjects. AB - Epinephrine 2% drops were administered to one eye and a placebo to the fellow eye twice a day for 2 weeks in 18 normal human volunteers. The circadian rhythm of aqueous humor flow was measured by fluorophotometry. Epinephrine (compared with placebo) had no measurable effect on the rate of aqueous flow or the circadian rhythm of aqueous humor flow. These results suggest either that topical application of epinephrine cannot achieve a sustained effect on the mechanism of aqueous formation compared with endogenous epinephrine or that circulating epinephrine is not the sole or principal hormonal messenger that mediates the circadian rhythm of aqueous flow in humans. An experiment in which epinephrine was administered systemically might clarify this ambiguity. PMID- 1869406 TI - Effects of hydrogen peroxide-induced oxidative damage on outflow facility and washout in pig eyes. AB - Previous studies show that hydrogen peroxide (H2O2) is present in the aqueous humor of many species and is capable of affecting outflow facility in animal model experiments. To study the hypothesis that oxidative damage to the outflow pathway may play a role in the pathogenesis of primary open-angle glaucoma, 3 mM H2O2 with 20 mM 3-aminotriazole and 1 mM carmustine (BCNU) in Dulbecco's phosphate-buffered saline (DPBS) was perfused into enucleated pig eyes at constant pressure. Baseline and experimental perfusions were done at two different pressures (7.5 and 30 mm Hg) to study the effect of pressure on the response to oxidative damage. Outflow facility in the baseline experiments (with DPBS only) was observed to increase nonlinearly with time during the perfusions, but could be linearized if plotted as a function of the volume perfused. Thus, a term "volumetric washout" (W) was introduced and defined as the fractional rate of change of outflow facility with respect to the volume perfused. This quantity was found to be independent of pressure in the baseline studies. Perfusion of H2O2 and inhibitors increased W at 7.5 mm Hg but decreased W at 30 mm Hg. These results indicate that oxidative damage increases outflow facility at normal pressure but decreases it at elevated pressure, suggesting that elevated pressure may increase the susceptibility of the outflow pathway to this form of insult. PMID- 1869407 TI - High-pass resolution perimetry in optic neuritis. AB - The topography of visual field defects resulting from optic neuritis as measured by spatial resolution perimetry is not known. Using high-pass resolution perimetry, the number and severity of visual field defects in the central visual field was determined in 18 patients with resolved optic neuritis and 18 age matched controls. Comparisons were made between three groups of eyes: (1) the involved eyes of the patients, (2) the uninvolved eyes of the patients, and (3) the eyes of the controls. Concentric zone analysis showed the involved eyes to have depression of the visual field in all zones with slightly more loss centrally. The "uninvolved" eyes showed a mild equal depression in all zones. Spatial resolution acuity measurements (which correlate directly with the spatial separation of retinal ganglion cell receptive field centers) indicated that the percentage of functioning retinocortical channels for normal eyes, uninvolved eyes, and involved eyes were 112%, 94%, and 58% of the reference normal values, respectively. These differences were all statistically significant. Resolution perimetry of the central visual field of eyes with resolved optic neuritis involves the cecocentral and Bjerrum areas. The loss was often patchy and a combination of cecocentral and arcuate defects. There was also a mild generalized depression of the uninvolved eye. PMID- 1869408 TI - Cone electroretinographic change during light adaptation in retinitis pigmentosa. AB - Cone electroretinograms (ERGs) to 30-Hz full-field white light were recorded after dark adaptation from 33 patients with retinitis pigmentosa and 8 normal subjects over a period averaging 8.5 min. Most patients and all normal subjects showed increases in amplitude that approached or reached maximum by the end of the recording. Regression analyses revealed that patients with smaller baseline amplitudes tended to show larger and faster increases in relative amplitude than patients with larger baseline amplitudes, whose amplitude changes over time were comparable to those seen in normal subjects. These findings suggest that both the magnitude and kinetics of cone ERG amplitude change to a light-adapting, flickering stimulus are related directly to the level of cone malfunction in retinitis pigmentosa. PMID- 1869409 TI - Taurine uptake in apical membrane vesicles from the bovine retinal pigment epithelium. AB - Characteristics of taurine uptake were investigated in apical membrane vesicles isolated from bovine retinal pigment epithelium. Uptake of taurine into these vesicles was stimulated markedly by the presence of an inwardly directed NaCl gradient across the membrane. The time course of the NaCl gradient-dependent uptake showed an overshoot, indicating a transient accumulation of taurine in the vesicles against a concentration gradient. Monovalent cations other than Na+ did not support taurine uptake. There was also an anion requirement for the uptake system, and Cl- was the most potent among several monovalent anions tested. The NaCl-dependent taurine uptake was stimulated by inside-negative, K+, and H+ diffusion potentials, demonstrating the electrogenic nature of the system. Stoichiometric analysis revealed that two Na+ and one Cl- ions were involved in the translocation of one taurine molecule. The system had an apparent dissociation constant (Kt) of 96 +/- 17 microM and a maximal velocity of 267 +/- 24 pmol/mg of protein over 15 sec. Uptake of radiolabeled taurine was inhibited by excess amounts of unlabeled taurine, hypotaurine, beta-alanine, and gamma aminobutyric acid. The relative potencies of the amino acids to inhibit taurine uptake were compared in three tissues, the bovine retinal pigment epithelium, the rat kidney, and the human placenta. In the apical membrane vesicles of the pigment epithelium, gamma-aminobutyric acid was many times more potent than taurine itself in inhibiting radiolabeled taurine uptake. However, in the brush border membrane vesicles of the kidney and the placenta, taurine was many times more potent than gamma-aminobutyric acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869410 TI - Analysis of normal flicker sensitivity and its variability in the visuogram test. AB - Flicker sensitivity was measured in groups of younger and older adult observers to assess its mean values and the test-retest variability both between sessions and in a single session. Test-retest sensitivities differed by less than 15% but tended to decrease slightly in a session and increase slightly between sessions. Optical blur had little effect on the measured sensitivities, implying that they were not mediated by the edge information in the display. There were no significant differences between eyes other than those attributable to testing order. Within eyes, inherent variations in human flicker sensitivity accounted for about half of the variance, and within-session variability accounted for most of the remainder. PMID- 1869411 TI - The lifetime cumulative incidence of acute anterior uveitis in a normal population and its relation to ankylosing spondylitis and histocompatibility antigen HLA-B27. AB - The lifetime cumulative incidence of acute anterior uveitis (AAU) was determined in a sample of a large population (n = 10,500). Nine hundred seventeen subjects, who answered the question "Have you ever had a red eye" in the affirmative in 1977, were asked to participate in a follow-up study 10 years later. From the 917 respondents, 539 were studied completely. A questionnaire was used to collect historic data, and confirmation of these data was obtained from the treating ophthalmologists and physicians. From these data, subjects were selected for an ophthalmologic examination. The respondents also underwent a rheumatologic examination. The results revealed that the lifetime cumulative incidence of definite AAU is approximately 0.2% in the general population and 1% in the histocompatibility antigen HLA-B27-positive population. In one third of the definite AAU patients, the cause of the disease was known. The lifetime cumulative incidence of definite AAU of unknown cause was 0.15% in the general population. When possible and probable AAU are included, the lifetime cumulative incidence of AAU in the general population is about 0.4%. The observed frequency of the concurrence of AAU and ankylosing spondylitis (AS) was 0.4% in the HLA-B27 positive population and 0.02% in the HLA-B27-negative population. Comparison with the expected frequency of the concurrence of AAU and AS revealed that AAU and AS probably are related diseases irrespective of the association of both diseases with HLA-B27. PMID- 1869412 TI - Relative contributions of epithelial cells and fibers to rabbit lens ATP content and glycolysis. AB - The adenosine triphosphate (ATP) content was measured independently in separated capsule-epithelium and fibers from whole rabbit lenses, both fresh and after incubation under various combinations of glucose and oxygen deprivation. Lactate production was also measured during aerobic and anaerobic incubations of whole lenses and of monolayers of cultured epithelial cells. The fresh capsule epithelium contained 3.3 nmoles ATP, whereas the decapsulated lens contained 410 nmoles ATP, a value that was indistinguishable from that of the whole, intact lens. In the presence of glucose, the fibers and epithelium each maintained their respective ATP content under aerobic and anaerobic conditions. In the absence of glucose, the ATP content in each fraction declined with time, but only in the epithelium was the rate of decline of ATP significantly faster in nitrogen than in oxygen. In whole lens, the rates of anaerobic and aerobic lactate production were similar, whereas in the cultured epithelial monolayers, the anaerobic rate was two-fold greater than in oxygen. From this it is concluded that approximately 50% of the ATP of the epithelial cells is derived from oxidative metabolism. A Pasteur response shown here for the first time with the cultured epithelium allows these cells to compensate for the loss of ATP production when mitochondrial oxidation is curtailed. The epithelium does not contribute to the ATP content of the lens fibers under aerobic or anaerobic conditions. PMID- 1869413 TI - Influence of culture conditions on the androgen control of secretory component production by acinar cells from the rat lacrimal gland. AB - Research has shown that androgens regulate the production of secretory component (SC), the IgA antibody receptor, by lacrimal gland acinar cells in vivo. This study was designed to establish an optimal culture system to permit analysis of this endocrine-acinar cell interrelationship in vitro. Acinar cells were isolated from male rat lacrimal glands and cultured on Matrigel (Collaborative Research, Bedford, MA) in serum-free Dulbecco's modified Eagle's medium (DMEM)/Ham's F12 media that contained a variety of supplements. Under these conditions, acinar cells responded to dihydrotestosterone (DHT) exposure with a significant increase in SC output. Replacement of the DMEM/Ham's F12 media base with either Modified Eagle's Medium (MEM) or low-calcium MEM inhibited this hormone response and dramatically reduced cell recovery after 4 days of culture. Similarly, decreased concentrations or deletions of selected media supplements, including insulin, which binds to acinar cells, and dexamethasone, led to a significant diminution in the extent of androgen action, as well as to a decline in cell maintenance. In contrast, removal of high-density lipoprotein from culture media or the addition of fetal bovine serum (FBS) or cholera toxin significantly enhanced basal and DHT associated SC production by acinar cells. With regard to extracellular matrices, Matrigel proved to be superior to collagen type I, laminin, fibronectin, or the Primaria (Falcon, Oxnard, CA) plastic surface in providing support for acinar cell association or hormone-related function. In summary, our results show that the media formulation, supplement profile, and extracellular matrix composition are important for maximal expression of androgen-induced effects by lacrimal gland acinar cells in vitro. PMID- 1869414 TI - The prenatal development of the optic fissure in colobomatous microphthalmia. AB - The coloboma in the cinnamon mouse homozygous for the microphthalmia gene is caused when optic fissure closure, which normally occurs between the 11th and the 13th gestational day, does not occur. This study sought to determine the cause of this fusion failure, and to identify any foci of fusion that occur later in gestation. Microphthalmic fetuses from the 11th-20th gestational day were obtained by datemating cinnamon mice heterozygous for the microphthalmia gene. Coronal serial sections of the eyes were examined at light and electron microscopy. Initially, the fissure margins became apposed only in the posterior aspects of the eye. A failure of basement membrane disintegration at the fissure margins prevented fusion at the 12th and 13th days. On the 14th day, small foci of basement membrane disintegration were identified in the area of the developing optic disc. Although the fusion zone enlarged later in gestation, it was limited to the area of the optic disc and showed that the two retinal layers did not separate. This study has shown that abnormal growth and invagination lead to delayed apposition of the optic fissure margins. These features together with a failure of basement membrane disintegration appear to be the main factors involved in coloboma formation. It is suggested that the excessive number of outer-layer cells that are inverted into the fissure, as well as abnormal or reduced numbers of phagocytic cells, may affect the persistence of the basement membrane. Alternatively, a primary defect of the pigment epithelial cell may lead to the development of the hypercellular and nonpigmented outer layer associated with the lack of basement membrane disintegration and nonfusion in this mutant. PMID- 1869415 TI - Tissue distribution of type VIII collagen in human adult and fetal eyes. AB - The type VIII collagen tissue distribution in human adult (32-78 yr of age) and fetal (16-27 weeks of gestation) eyes was studied immunohistochemically using a monoclonal antibody to type VIII collagen. Type VIII collagen was distributed in a linear or fibrous fashion in adult eyes in Descemet's membrane of the cornea, the trabecular meshwork, the walls of Schlemm's canal, Bruch's membrane, the choroidal stroma, the sclera, the cribriform plates of the optic nerve, and the intima of the central retinal artery. The staining in the central retinal artery was similar to that of type IV collagen. No distinct positive staining was seen in other blood vessels. When fetal eyes were examined, significant differences in positive staining were found between adults and fetuses in the sclera. In fetal eyes, the posterior sclera was strongly stained; however, the positive staining gradually decreased, and in the equatorial area it disappeared. The cribriform plates of the lamina cribrosa and the presumptive Bruch's membrane in fetal eyes did not react with the antibody. The trabecular meshwork and Descemet's membrane, but no other part of anterior section of fetal eyes, reacted with the antibody. PMID- 1869416 TI - The time course of interocular suppression in normal and amblyopic subjects. AB - The authors measured the time course of interocular suppression of five normal subjects and eleven patients with amblyopia (strabismic and/or anisometropic). Orthogonal gratings were presented dichoptically for durations that ranged from 10-6000 msec. All normal observers reported fusion or superimposition of the orthogonal gratings for short stimuli and reported binocular rivalry for stimuli longer than 150 msec. At long presentation times, all amblyopes constantly suppressed the pattern that was presented to their amblyopic eye. Six amblyopes showed superimposition of the two patterns at short presentation times. Of these, three had time courses similar to those of normal observers; the other three had a much shorter onset of suppression (about 80 msec). The remaining five amblyopes perceived only the pattern of the dominant eye at short stimulus durations; at intermediate durations, they reported partial superimposition of the stimuli, whereas at the longest stimulus durations, again only the stimulus of the dominant eye was perceived. The results suggest that binocular rivalry in normal observers and strabismic suppression in amblyopes are mediated by different mechanisms. The heterogeneity of the time courses of suppression in amblyopes might result from differences in the disturbances of early visual development (age at onset of strabismus and/or anisometropia, origin, and therapy). PMID- 1869417 TI - Analysis of eye lens-specific genes in congenital hereditary cataracts and microphthalmia of the miniature schnauzer dog. AB - The congenital hereditary cataracts and microphthalmia in the miniature schnauzer dog are inherited by an autosomal recessive mode. To understand the genetic basis of these diseases, the authors purified and analyzed leukocyte deoxyribonucleic acid (DNA) from affected and normal animals using a candidate gene approach. Because the genes that encode the lens-specific proteins, specifically, alpha, beta, and gamma crystallins and the membrane protein (MP26), are known to maintain the structure and function of the lens, the authors used complimentary DNA (cDNA) fragments that corresponded to the above genes to search for the mutations at their loci in the affected animals. They found no evidence of the gene deletion and rearrangement in any of the five loci. In addition, the hybridizable sequences of the dog DNA to the specific probes for the human chromosome 4 and 18 loci, which are reported to be involved in the abnormality of the human eye, seem to be unaffected. These data support the notion that the hereditary cataracts and microphthalmia in the dog may be associated with genes other than those reported for several animal systems. PMID- 1869418 TI - Radiographic interpretation of tonsiliths. PMID- 1869419 TI - What's new in dermatology? New topical agents. PMID- 1869420 TI - What's new in dermatology? Management of congenital melanocytic nevi. PMID- 1869421 TI - What's new in dermatology? Outpatient treatment of severe psoriasis. PMID- 1869422 TI - What's new in dermatology? Pulsed dye laser treatment for port wine stain birthmarks. PMID- 1869423 TI - What's new in dermatology? Sweating problems. PMID- 1869424 TI - What's new in dermatology? Cutaneous lymphoma. PMID- 1869425 TI - Skin cancer: diagnosis and management. AB - Patients should be encouraged to adopt sun protective habits and have new or changing skin lesions evaluated promptly. Physicians should thoroughly examine all of the skin and be prepared to assess individual risks for skin cancer. When the issue is in doubt, skin biopsy or a more detailed examination by a skin specialist is recommended. Educational campaigns directed toward prevention and early detection of skin cancer can greatly reduce the morbidity and mortality of this very common disease. PMID- 1869426 TI - Lyme disease: the picture in Iowa. AB - Lyme disease in Iowa increased sharply in 1989 and 1990, creating concern in Iowans who spend considerable time out-of-doors. The authors review the history of Lyme disease and its symptoms and present an update on the status of Lyme disease and its tick vector in Iowa. PMID- 1869428 TI - Screening and prevention of skin cancer. PMID- 1869427 TI - Infective endocarditis in Iowa. AB - This review of 43 cases of infective endocarditis (IE) treated at a large Iowa community hospital reveals an incidence of 9 cases per 22,000 annual admission. IE is most likely to occur in an elderly male with non-specific symptoms and signs and involvement of the mitral valve infected with streptococci. PMID- 1869429 TI - Uniformity of results reporting in head and neck cancer. PMID- 1869430 TI - Time to recurrence of squamous cell carcinoma of the head and neck. AB - A personal series of 3,215 patients with proven squamous cell carcinoma of the mucosal surfaces of the upper aerodigestive tract is presented. Of these patients, 515 suffered a recurrence of their primary tumor after a course of radiotherapy. The time from the end of radiotherapy to diagnosis of a primary recurrence was not related to any known host factors, nor to tumor factors except site. However, it was the most significant predictor of survival, both from initial presentation and from the date of recurrence. The time to recurrence did not relate to the size of the tumor at recurrence, suggesting that large recurrences are multicentric. The time to recurrence also predicted response and survival of 67 patients with end-stage disease treated by chemotherapy. The response and survival were better in tumors with a time to recurrence longer than the median; the increased survival was not significant, but the increased response was. PMID- 1869431 TI - Prognostic value of paranasopharyngeal extension of nasopharyngeal carcinoma on local control and short-term survival. AB - The local tumor control of 262 patients with nasopharyngeal carcinoma (NPC) at median follow-up of 27 months was studied with reference to the paranasopharyngeal and other aspects of extranasopharyngeal extension of tumor, as well as to other possible prognostic factors. Only cranial nerve palsy, oropharyngeal involvement, and paranasopharyngeal extension of tumor were found to be significant in a multivariate analysis using Cox model for factors influencing local tumor control. Other factors and other parameters of extranasopharyngeal extension of tumor, namely, erosion of the base of skull, intracranial extension, and involvement of nasal fossa, were found not be significant. The degree of paranasopharyngeal extension in each side was correlated with scales measuring extranasopharyngeal extension of tumor in other directions (p = 0.001). Although the T stage and the paranasopharyngeal extension were individually found to be well correlated with local tumor control, the prognostic value of paranasopharyngeal extension remained significant among subgroups of patients with T3 and T4 disease (p = 0.1044 and 0.0010, respectively). PMID- 1869432 TI - Antibiotic prophylaxis in cranial base surgery. AB - The role of perioperative antibiotic prophylaxis was investigated in 95 patients undergoing 100 clean-contaminated cranial base surgeries. A variety of antibiotic regimens were employed. Potential risk factors for local infection were analyzed. Seven patients (7%) developed infections at the surgical site (meningitis, intracranial abscess, cellulitis/abscess, and osteomyelitis). Antibiotic prophylaxis for 24 hours or less was associated with a significantly increased risk of infection (p less than 0.04). Prolonged antibiotic prophylaxis (greater than 48 hours) was not more efficacious than prophylaxis for 48 hours. The surgical approach, type of reconstruction, duration of surgery, and use of drains were not significantly correlated with wound infection. The risk of intracranial infection following cranial base surgery is low despite the presence of bacterial contamination intraoperatively. Broad-spectrum coverage of gram-positive and gram negative organisms for at least 48 hours is recommended. Attention to surgical technique is important in preventing infectious complications. PMID- 1869433 TI - Laryngeal flap for hypopharynx reconstruction. AB - Hypopharynx repair following resection of a pyriform sinus carcinoma may be accomplished primarily or involve a more extensive procedure, such as a free intestinal graft. Described herein is a laryngeal flap which may be used to repair a hypopharyngeal defect when a strip of mucosa, too narrow for a primary repair, is left. This method has been used successfully in 4 patients and has saved these patients from more extensive repairs. PMID- 1869434 TI - Esthesioneuroblastoma: is there a role for elective neck treatment? AB - A retrospective review of the Memorial Sloan Kettering Cancer Center experience (MSKCC) with esthesioneuroblastoma was performed. From 1975 to 1985 14 cases were identified. Overall 5- and 10-year survival was 86% and 70%, respectively. Four local failures were observed and 4 neck failures were observed. A review of the literature since 1966 revealed an unexpectedly high incidence of neck failure, and of the 21 of 110 patients with neck failures that were identified through the literature, there were 6 subsequent deaths. PMID- 1869435 TI - Fundamentals of expanded tissue. AB - The relatively recent advent of tissue expansion for medical purposes precludes the availability of extensive knowledge concerning the physiologic and histologic changes that occur during controlled expansion of the skin. This paper reviews the basic science and clinical research that has been conducted to investigate the changes and summarizes the findings. It can be concluded that flaps harvested from skin previously expanded have an improved survival rate compared to similar flaps developed in nonexpanded skin. Increased vascularity to either the skin, the capsule that forms around the expander, or both probably in some way accounts for the improved survival. Controlled expansion of the skin results in the creation of additional new skin at the expense of thinning the dermis and subcutis. This thinning is associated with an overall decrease in tensile strength of the expanded skin. The increase in surface area gained from skin expansion probably varies according to the type of skin expanded and the underlying tissues that serve as a foundation for the expander. PMID- 1869436 TI - Speech patterns following partial glossectomy for small tumors of the tongue. AB - To determine the type and extent of speech impairment to be expected following partial glossectomy, pre- and postoperative speech evaluations were performed on 10 patients undergoing surgery for carcinomas of the mobile tongue less than 3 cm in size. In addition, audiotapes of standardized speech samples were made at each evaluation. Preoperative speech evaluation revealed normal rates of verbal diadochokinesis without distortion in all 10 patients. Phonologic analysis was also normal in 9 of these patients. Postoperative evaluation revealed normal rates of verbal diadochokinesis in 6 patients and mild lingual distortion in 4. At 3 weeks postoperatively 1 patient had sibilant distortion and 1 patient overall slurring of speech. Evaluation of both of these patients at 6 months revealed that speech had returned to normal. Blinded comparison of the pre- and postoperative audiotapes revealed no change in 8 patients. In 2 patients the early postoperative tape was thought to "sound different" but the final postoperative tapes in all patients were judged to be normal. This study demonstrates that partial glossectomy for early carcinomas of the tongue can be performed with minimal, if any, permanent speech impairment. PMID- 1869437 TI - Labeling index in squamous cell carcinoma of the larynx. AB - Two cell kinetic parameters, the 3H-thymidine labeling index (TLI) and the mitotic index (MI), were studied in vitro on fragments of squamous cell carcinoma tissue of the larynx. They were evaluated to identify those elements able to characterize the growth of these solid tumors. The values of these parameters were analyzed as a function of the clinical stage and the involvement of the regional lymph nodes. Results showed a statistically significant increase in the TLI from stage T1 to T3. No statistically significant differences in the TLI values were observed between the patients with positive and negative lymph nodes. PMID- 1869438 TI - Temporal bone involvement by prostatic adenocarcinoma: report of two cases and review of the literature. AB - Although axial bone and cranial metastases are common in patients with prostatic carcinoma, temporal bone involvement is rare. We report 2 cases of prostatic adenocarcinoma with temporal bone metastasis and review the relevant literature. One case had a 3-year history of a prostatic carcinoma, whereas in the second case the temporal bone metastasis was the initial presentation. Awareness of the possibility of temporal bone involvement by prostate carcinoma and application of immunohistochemical studies will help to arrive at the correct diagnosis. PMID- 1869439 TI - Lymphoma of the maxillary sinus in a patient infected with human immunodeficiency virus type 1. AB - A 27-year-old woman with a history of intravenous drug abuse presented with a stage IE, diffuse, large cell lymphoma of the right maxillary sinus. A test for antibodies to the human immunodeficiency virus was positive. The patient was treated with systemic chemotherapy and local maxillary sinus irradiation which resulted in complete regression of the disease. Therapy was complicated by mucositis, neutropenia, and opportunistic infections. This is the first case report to discuss the presentation and treatment of acquired immunodeficiency syndrome (AIDS)-related lymphoma of the maxillary sinus. PMID- 1869440 TI - Increased intracranial pressure as a complication of unilateral radical neck dissection in a patient with congenital absence of the transverse sinus. AB - We report a patient with increased intracranial pressure occurring after unilateral neck dissection. Subsequent vascular studies reveal a hypoplastic contralateral transverse sinus drainage and occlusion of the ipsilateral jugular bulb. We review the literature on the etiology of this vascular malformation and conclude that vascular anomalies of the venous drainage of the head be considered whenever postoperative signs of increased intracranial pressure occur after unilateral radical neck dissection. PMID- 1869441 TI - Obstructing laryngeal carcinoma with a simultaneous lung lesion. AB - The consultants all agree to treat this patient who has a seemingly poor prognosis. However, they disagree as to the method and order of treatment. A patient's nutritional status is taken seriously by all 3 experts, although no one would delay surgery to correct a patient's weight loss. Drs. Komisar and Miller consider a weight loss of 10% significant and prefer to assess a patient with lymphocyte counts, serum albumin and transferrin levels, and creatinine/height index. Dr. Osguthorope follows serum hemoglobin, transferrin, prealbumin, and albumin levels. All the experts prefer an enteral route for weight gain. With regard to diagnosis, the experts agree that endoscopy plays an important role in tumor staging. Drs. Komisar and Osguthorpe believe that a tracheotomy should be performed prior to endoscopy. Dr. Miller would prefer intubation with an endotracheal tube but if there were any question of safety, he would proceed with a tracheotomy under local anesthesia. Confirming the histology of the pulmonary lesion is important. Dr. Komisar would proceed with flexible bronchoscopy and if tissue could not be obtained with this method he would obtain a fine-needle biopsy. He believes that if the histology matches that of the larynx, the pulmonary lesion is a metastasis. Dr. Osguthorpe would also obtain a needle biopsy of the lung lesion. If no other lesions are seen on the CT, he would consider this a second primary. Dr. Miller states that unless the histologies are different, the question of primary vs metastatic disease is unanswerable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869442 TI - Modeling organizational determinants of hospital mortality. AB - This study examines hospital characteristics that affect the differential in hospital mortality. Death rates for 1984 Medicare inpatients in acute care hospitals, released by the Health Care Financing Administration in 1986, were analyzed. A confirmatory statistical approach to organizational determinants of hospital mortality was formulated and validated through an empirical examination of 239 hospitals. The findings suggest that the effect of hospital size and specialization on mortality was a spurious one when the effects of other variables were simultaneously controlled. A positive association existed between service intensity and hospital mortality: the more hospital services consumed, the higher the mortality rate. Community attributes accounted for more variance in hospital mortality rates than did organizational attributes. The organizational and community factors studied explained 27 percent of the total variance in hospital mortality. PMID- 1869443 TI - The cesarean birth rate: influence of hospital teaching status. AB - Knowledge of how cesarean birth rates vary by hospital characteristics may aid in understanding and perhaps modifying some of the structural and process components of newborn delivery services to decrease the necessity of birth by cesarean procedure. To examine the influence of select hospital characteristics, data on hospital newborn deliveries in Illinois for 1986 among women 10-50 years of age inclusive (N = 130,249) were obtained from computerized hospital discharge abstract files. Characteristics of the hospitals were obtained from the annual American Hospital Association survey. Adjusting for mother's age at delivery; presence of pregnancy, labor, and delivery complications; expected primary payer; and size of hospital, women delivering in hospitals with teaching status were less likely (odds ratio = 0.76, p less than .001, 95 percent CL: 0.73, 0.79) to have a primary cesarean birth than women delivering in hospitals without this designation. A significantly lower cesarean birth rate in teaching hospitals was also observed in women of all age groups, in Medicaid and non-Medicaid women, and for most categories of delivery complications. These data suggest the need to identify the programmatic, technologic, and manpower functions associated with hospital teaching status that could decrease the likelihood of a primary cesarean delivery. The study also suggests that changes aimed at the manner of diagnosis, monitoring, and/or management of pregnancy/delivery complications may reduce the cesarean birth rate because of large differences in the primary cesarean birth rate found between teaching and other hospitals for most categories of newborn delivery complications. PMID- 1869444 TI - Waiting for placement: an exploratory analysis of determinants of delayed discharges of elderly hospital patients. AB - This article examines the causes of delayed hospital discharge for 3,111 patients waiting for alternative placement in 80 North Carolina acute care general hospitals during May 1989. Almost all of the patients were elderly: their average age was 77. Delay is defined as the period between the day a patient was judged medically ready for discharge by a discharge planner and the day the patient was discharged (or May 31 if unplaced). The average delay was 16.7 days. The policy relevant patient characteristics associated with delay are requirement for heavy care, race, source of reimbursement, and whether or not there was a financial problem in arranging discharge. The patient's age and whether or not a problem with behavior or family cooperativeness was noted also were predictors. Along with patient characteristics, hospital features such as bed size, occupancy rate, and total revenues were correlated with delay. Local nursing and rest home (domiciliary) bed supply were insignificant predictors, possibly because of their limited variance: the number of nursing home beds in all North Carolina counties is below the national mean; the number of rest home beds exceeds it. The conclusion reached is that the delay problem warrants more intensive analysis, particularly regarding financial problems encountered at discharge, and race. Guidelines for such an endeavor are provided. Further, there is a need to recognize the increasing preponderance of a new type of heavy care patient via more appropriate reimbursement levels and "transitional care" services. PMID- 1869445 TI - Physician participation in hospital strategic decision making: the effect of hospital strategy and decision content. AB - An exploratory study examined variation in the participation of physicians in hospital strategic decision making as a function of (1) strategic decision content or (2) hospital strategy, or both. The findings revealed that who participates is a function of decision content while how physicians participate is a function of decision content and the interaction of decision content and hospital strategy. PMID- 1869446 TI - A method for enzyme- and immunohistochemical staining of large frozen specimens. AB - A method for large specimen cryosectioning is described. Specimens of pig heart ventricles were lightly fixed by microwave irradiation, embedded in 10% gelatin, frozen in hexan chilled with dry ice, and sectioned using an LKB 2250 PMW cryomicrotome. The sections were collected on transparent film and transferred onto glass slides. Standard histological, enzyme- and immuno-histochemical staining techniques were used. The present method allowed cryosectioning with sections of good quality which could be used for enzyme- and immuno-staining. For studies of experimental myocardial infarction, staining for phosphorylase and Periodic Acid Schiff outlined the ischemic area and antibodies against plasma fibronectin and fibrinogen delineated the infarcted myocardium. PMID- 1869447 TI - Immunoreactive calbindin-D9K in bone matrix vesicle. AB - This electron microscope study describes the subcellular occurrence and distribution of immunoreactive calbindin-D9K in the trabecular metaphyseal and compact cortical bone of normal rats, rachitic vitamin-D-deficient rats, and rachitic rats given 1,25-(OH)2D3. Undecalcified bones were embedded in Lowicryl K4M and calbindin-D9K antigenicity was detected by the protein A-gold method. Immunoreactive calbindin-D9K was localized in the cytoplasm and cell processes of osteoblasts and osteocytes. Immunoreactive calbindin-D9K was also found within matrix vesicles and calcifying matrix vesicles, where it lay over the needle shaped crystallites, at the apparent site of initial crystal formation, but not along the whole crystallites. In fully mineralized bone it occurred at the same site, over the crystallites. Calibindin-D9K was vitamin-D-dependent in the osteoblasts and matrix vesicles, where its presence was correlated with the reappearance of crystallites in 1,25-(OH)2D3-treated vitamin-D-deficient rats. This suggests that immunoreactive calbindin-D9K is involved in mineral deposition in bone matrix vesicles. Abnormal intracellular calcification associated with calbindin-D9K antigenicity in the osteoblasts of 1,25-(OH)2D3-treated vitamin-D deficient rats indicates that immunoreactive calbindin-D9K may also play a part in abnormal intracellular mineral deposition. PMID- 1869448 TI - Epidermal growth factor in the rat lung. AB - Epidermal Growth Factor (EGF) in pharmacological doses is able to induce precoccious lung maturation in rabbits and sheeps. As EGF is probably acting in a para- or autocrine way, we have searched for EGF in the lungs. We report EGF immunoreactivity to be present in the type II pneumocytes of the rat from a couple of days prior to birth and throughout life. Further, we report EGF immunoreactivity to be present in cells in the bronchi and the bronchioles from day 20-21 of gestation and throughout life. G-200 gelchromatography of lung extracts indicates that the EGF-reactive material is a high molecular weight form of EGF. Since previous studies have shown that EGF in pharmacological doses is able to promote lung maturation, our results may imply a physiological role for EGF in the lungs. PMID- 1869449 TI - Ultrastructural detection of DNA-incorporated bromodeoxyuridine in resin embedded brain tissue. AB - We describe a protocol for the ultrastructural detection of DNA-incorporated bromodeoxyuridine (BUdR) in resin embedded tissue by means of post-embedding immunogold labeling. The paraventricular zone of rat embryos brains was dissected, fixed either in paraformaldehyde or glutaraldehyde, and embedded in LR White. BUdR gold labeling was only found when thin sections were pretreated with 4 N HCl. Other DNA denaturing agents, such as Na ethoxide, formamide, formic acid, heat or HCl at lower concentrations were ineffective. Very little difference in the degree of labeling was found depending on the fixation. This method can be applied to investigate the fine structure of replicating cells in other in vivo conditions, such as human tumors. PMID- 1869450 TI - A diurnal variation of vasoactive intestinal peptide (VIP) mRNA under a daily light-dark cycle in the rat suprachiasmatic nucleus. AB - We detected a diurnal change of vasoactive intestinal peptide (VIP) messenger RNA (mRNA) in the rat suprachiasmatic nucleus (SCN) using the in situ hybridization technique combined with computed image analysis. The amount of VIP mRNA was greatest at 02.00 h, the next largest level was seen at 20.00 h during the dark phase and smallest at 14.00 h during the light phase. We also confirmed that the onset of the fluctuation of mRNA occurred 2-6 h prior to the diurnal variation of the content of VIP-like immunoreactivity by semiquantitative immunocytochemistry. These findings suggest that light stimulus from the retina is a primarily influence on the transcription of VIP mRNA and induces a diurnal variation of VIP synthesis. PMID- 1869451 TI - Paneth cell degranulation and lysozyme secretion during acute equine alimentary laminitis. AB - The equine Paneth cell response to a shift in the microbial balance of the intestinal tract was studied by inducing an acute episode of alimentary laminitis in 6 mature ponies. The normal bacterial population of the gut was modified by administration of a carbohydrate-rich ration. During acute laminitis a dramatic degranulation of the Paneth cells occurred in the intestinal glands throughout the duodenum, jejunum, and ileum. Bacteriocidal lysozyme, which was immunohistochemically identified as a component of the Paneth cell secretory granule, was evident in the glandular lumina and in degranulated Paneth cells. These results indicate that lysozyme is secreted by the equine Paneth cell in an apparent attempt to regulate the changing microbial population induced by carbohydrate overload of the gut. From these observations, it is suggested that the Paneth cell plays a role in the mucosal defense system of the equine intestinal tract. PMID- 1869452 TI - The effect of local control on metastatic dissemination in carcinoma of the prostate: long-term results in patients treated with 125I implantation. AB - The study evaluates the effect of the locally recurring tumor on the incidence of metastatic disease in early stage carcinoma of the prostate. The probability of distant metastases was studied in 679 patients with Stage B-C/N0 carcinoma of the prostate treated at MSKCC between 1970 and 1985 (median follow-up of 97 months). Patients were staged with pelvic lymph node dissection and treated with retropubic 125I implantation. The actuarial distant metastases free survival (DMFS) for patients at risk at 15 years after initial therapy was 37%. Cox proportional hazard regression analysis of covariates affecting the metastatic outcome showed that local failure, used in the model as a time dependent variable, was the most significant covariate, although stage, grade, and implant volume were also found to be independent variables. The relative risk of metastatic spread subsequent to local failure was 4-fold increased compared to the risk without evidence of local relapse. The 15-year actuarial DMFS in 351 patients with local control was 77% compared to 24% in 328 patients who developed local relapses (p less than 0.00001). The relation of distant spread to the local outcome was observed regardless of stage, grade, or implant dose. Even stage B1/N0-Grade I patient with local control showed a 15-year actuarial DMFS of 82%, compared to 22% in patients with local relapse; p less than 0.00001). The median local relapse-free survival (LRFS) in the 268 patients with local recurrences who did not receive hormonal therapy before distant metastases were detected was 51 months, compared to a median of 71 months for DMFS in the same patients (p less than 0.001), consistent with the possibility that distant dissemination may develop secondary to local failure. Furthermore, distant metastases in patients with local control, apparently already existing as micrometastases before treatment, were detected earlier (median DMFS of 37 months) than in patients with local relapse (median DMFS of 54 months; p = 0.009). These data suggest that the existence and re-growth of local residual disease in localized prostatic carcinoma promotes an enhanced spread of metastatic disease, and that early and complete eradication of the primary tumor is required if a long term cure is to be achieved, although the clinical expression of secondary metastases may not become apparent for 6.5 years or more in one-half of the patients. PMID- 1869453 TI - The effect of local-regional control on distant metastatic dissemination in carcinoma of the head and neck: results of an analysis from the RTOG head and neck database. AB - A retrospective analysis of the effect of local control on the development of distant metastases was performed in 2648 patients with carcinoma of the head and neck selected from the RTOG database. The 5-year time-adjusted incidence of distant metastases was 21% for patients who were in local-regional control at 6 months after the start of treatment, compared to 38% for local-regional failure patients (p less than 0.001). The incidence of distant metastases detected between the interval of 6 months to 2.5 years after treatment was significantly increased in patients with tumors of the oral cavity, oropharynx, supraglottic larynx, and glottis who developed local-regional failure within this time period, compared to those who remained locally controlled (19% distant metastases for local-regional failure vs 7% for local-regional control (p less than 0.001)). In contrast, there as no difference in the incidence of distant metastases in patients with carcinoma of the nasopharynx or hypopharynx regardless of the local regional disease status. A Cox proportional hazards regression analysis demonstrated that local-regional control was the most significant variable affecting the development of distant metastases, followed by tumor site, N-stage, and T-stage. For all tumor sites, except for the hypopharynx and nasopharynx, improvements in local-regional control are likely to improve survival. Tumors of the hypopharynx and nasopharynx have a higher probability of micro-metastatic dissemination at the time of initial diagnosis, and until effective methods to treat disseminated disease are developed, the effect of local control on survival will not be readily discerned. PMID- 1869454 TI - Prospective randomized trial comparing hyperfractionated versus conventional radiotherapy in stages III and IV oropharyngeal carcinoma. AB - From April 1986 to May 1989, 112 patients seen at a single institution with previously untreated squamous cell oropharynx carcinoma, Stages III and IV, were randomly assigned to 66 Gy in 33 fractions of 2 Gy each (conventional RT) versus 70.4 Gy in 64 fractions of 1.1 Gy given twice a day with a minimal interfraction interval of 6 hours (hyperfractionated RT). The overall time for both arms was 6 1/2 weeks. Patients were stratified by site (base of the tongue vs others), T stage (T1/T2 vs T3 vs T4), N stage (N0/N1 vs N2 vs N3), and lymphnode size (less than 6 cm vs greater than 6 cm). As of January 1990, an analysis was performed in 98 patients (8 patients in the conventional arm and 6 in the hyperfractionation not included). The groups were balanced by age, performance status, stage, and site of the primary disease. The median follow-up time was 25 months. The probability of complete loco-regional response was 62% in the hyperfractionation arm and 52% for the conventional fractionation (p = 0.28). There was no difference in the control of lymphnodal disease (hyperfractionated = 55%, conventional = 57%; p = 0.92), but the disease control in the oropharynx only was significantly improved in the hyperfractionation arm (84% vs 64%, p = 0.02). Overall survival rate at 42 months was 27% for the hyperfractionation arm and 8% for the conventional (p = 0.03). Survival rates for hyperfractionated versus conventional RT were 40% versus 18% (p = 0.06), respectively, for Stage III patients and 16% versus 0% (p = 0.15), respectively, for Stage IV. There was significant improvement in survival in favor of the hyperfractionation arm in patients with lesions outside the base of the tongue (31% vs 15%, p = 0.02), for those with a 50-70% Karnofsky status (19% vs 0%, p = 0.006) and for patients with N0/N1 disease (38% vs 15%, p = 0.03). Acute toxicities were of similar magnitude, although both skin and mucosal reactions appeared earlier on the hyperfractionation scheme. To date, no differences in late toxicity have been observed. We conclude that in a subset group of patients with locally advanced carcinoma of the oropharynx, hyperfractionated radiotherapy appears to provide improved survival without adding to increased toxicity. PMID- 1869455 TI - Accelerated superfractionated irradiation for advanced carcinoma of the head and neck: concomitant boost technique. AB - Between 1980 and 1988, 94 patients with AJCC Stage III and IV squamous cell carcinoma of all sites of the upper aero-digestive tract were treated with radiotherapy. We report here on 62 patients who are followed for a minimum of 2 years. Of these, 30 patients were treated with conventional once-a-day radiotherapy and 32 patients were irradiated using an accelerated superfractionation regimen during part of the treatment course. The altered fractionation schedule employed a concomitant boost technique with clinically demonstrable disease being irradiated twice-a-day during the first or second half of the treatment course. Daily radiation fractions were 1.8 Gy and the boost field was treated with 1.6 Gy after a 4- to 6-hr interval. No significant differences in acute treatment toxicity were observed in the two treatment groups. Patients treated with conventional and accelerated fractionation regimens experienced 36 months actuarial local tumor control rates of 40% and 67% (p = 0.03), respectively, which translated into an actuarial disease-free survival of 40% and 64% (p = 0.04). The increased locoregional control rates in patients treated with accelerated fractionation were associated with an adjusted and overall survival advantage at the p = 0.05 level. We conclude that our regimen of accelerated superfractionated irradiation with shortening of the treatment course resulted in improved control and survival rates at conventional doses of 68.4 to 73.8 Gy. PMID- 1869456 TI - The influence of extent of neck treatment upon control of cervical lymphadenopathy in cancers of the oral tongue. AB - This is a retrospective analysis of the management of the neck in 84 patients with squamous cell carcinoma of the oral tongue treated with curative intent between 1968 and 1985. Patients with a clinically negative neck were treated to the neck only if the patient was thought to have a reasonable probability of occult neck metastases. This policy resulted in a 3-year adjusted neck control rate for N0 patients treated with limited (no, bilateral-partial, or ipsilateral) neck therapy of 38% compared with 95% for patients treated with bilateral, whole neck irradiation (p less than .001). None of the relapses in the patients with limited irradiation were in the treatment portal. Attempted salvage with a neck dissection resulted in cure in only 30%. The 3-year adjusted neck control rate for the N1 and N2 patients treated with total neck irradiation and surgery was 75% and 63%, respectively. The location of recurrence in these patients was in the field of irradiation, but contralateral to the side of the neck dissection. PMID- 1869457 TI - Second neoplasms in patients with carcinomas of the vocal cord: incidence and implications for survival. AB - A retrospective analysis was performed for 218 patients who were managed for carcinomas of the glottic larynx from 1975 to 1988. With a median follow-up of 51 months (range: 24 to 120 months), 41 patients developed a second malignant neoplasm. Six patients had synchronous and 35 had metachronous second malignant neoplasms. The median interval between the diagnosis of glottic carcinoma and a second malignant neoplasm was 31 months. This median interval increased to 43 months when only the metachronous tumors were analyzed. The average annual risk of developing a second malignant neoplasm (SMN) in a 10-year period was 3.1%. Seventy-one percent of them occurred in the upper aerodigestive tract or lungs. When analyzed according to the initial stage of the glottic carcinoma, 23 of 145 (16%) patients with T1 or T2 glottic carcinomas developed a second malignant neoplasm, whereas 18 of 73 (25%) patients T3 or T4 lesions did so. For the T1/T2 group, the average annual risk was 2.5%, as compared to 4.8% for the T3/T4 group (p = 0.023). The development of a second malignant neoplasm adversely affected survival. The 10-year actuarial survival for these patients who did not develop a second malignant neoplasm was 45%, as compared to 19% for those who did develop a second malignant neoplasm (p = 0.008). Although second malignant neoplasms occurred in only 19% of the total patient population, their impact on the survival rate of the overall population was equal to that of glottic carcinomas. The median survival after the diagnosis of a SMN was 6 months. The high incidence of second malignant neoplasms in patients with glottic carcinomas warrants careful follow-up and clinical investigation of the use of chemopreventive agents. PMID- 1869458 TI - Cobalt60 plaques in recurrent retinoblastoma. AB - Cobalt60 plaque irradiation is one treatment option for patients with recurrent retinoblastoma following conventional external beam irradiation (ERT). Tumorocidal doses can be delivered without excessive risk of normal tissue injury. In patients not considered candidates for xenon arc or cryotherapy, 60Co is an alternative to enucleation. Between 1968 and 1987, 85 patients were treated with 60Co plaques, 72 of whom had failed prior ERT. Age at diagnosis ranged from 1 week to 4 years. There are 37 males and 35 females. Seventy-one patients had bilateral disease and one had unilateral. Three patients had both eyes plaqued. Prior ERT ranged from 30 to 70 Gy (mean 4200 Gy). Time from initial therapy to failure ranged from 13 to 60 months. Cobalt plaques of 10 mm, 15 mm, or 10 x 15 mm were used depending on tumor size and location. Dose prescribed to the apex of the tumor ranged from 30 to 50 Gy (median 40 Gy) given over 3 to 8 days. Twelve patients had two plaque applications; three patients had three plaque applications. All patients were followed with routine ophthalmoscopic examinations. Follow-up ranged from 2 to 22 years (mean 8.7). Seven patients died of metastatic disease; 10 patients developed non-ocular second tumors. Thirty patients required enucleation. Twenty-two patients had clear tumor progression, two patients had radiation complications, and six patients had a combination of tumor growth and complications. Cobalt60 can salvage eyes in retinoblastoma patients failing ERT. Currently, we are using I125 in an attempt to spare normal ocular tissue and reduce subsequent complications. PMID- 1869459 TI - Pancoast tumor: radiation therapy alone versus preoperative radiation therapy and surgery. AB - This is a retrospective analysis of 73 patients with non-oat cell carcinoma of the lung presenting as a Pancoast tumor. All patients were treated with curative intent between October 1964 and September 1987 (minimum follow-up 2 years). The treatment plan consisted of preoperative radiation therapy (usually 3000 cGy in 2 weeks or 4500 cGy in 5 weeks) in 41 patients and radiation therapy alone (usually 6500-7000 cGy in 6.5-8.0 weeks) in 32 patients. In general, radiation therapy alone was reserved for poor-prognosis patients (extensive disease or medical inoperability). Although 41 patients were initially scheduled to receive preoperative radiation therapy and surgery, the surgery was not performed in 12 cases (29%) because of patient refusal (4 patients), poor response to radiation therapy (4 patients), distant metastasis (2 patients), or debilitation (2 patients). Separate calculations were carried out for the patients who completed the surgery as planned (preoperative radiation therapy and surgery) and the entire group originally scheduled for combined-modality therapy. There was no significant difference in the absolute or cause-specific survival rates between treatment groups, but severe complications were significantly more common in patients receiving combined therapy. PMID- 1869460 TI - Estimation of clonogenic cell fraction in primary cultures derived from human squamous cell carcinomas. AB - Tumor clonogenic cell content is believed to play an important role in the outcome of radiotherapy. However, there is no proven method to assess the number of clonogens in human tumors accurately. All currently available assays employ in vitro plating efficiency or in vivo TD50 (the average number of cells needed to induce tumors in 50% of injected mice) to estimate the tumor clonogenic ability. In this study, a monolayer mass primary culture system was used to estimate the clonogenic cell fraction in human tumors. For this purpose, 25 growth curves were performed for 25 tumor specimens derived from 21 head and neck and 4 cervical squamous cell carcinomas. The exponential portion of each growth curve was extrapolated through the ordinate (day 0) to estimate the clonogenic cell fraction; this method is only an estimate because it assumes no lag phase before exponential growth of clonogenic cells. The mean clonogenic cell fraction, expressed as clonogens/tumor cells inoculated, was relatively low (mean: 0.71%, range: 0.11-9.28), and the variation was wide (coefficient of variation = 148%). On the other hand, the doubling time of the growing population was 1.46 days and exhibited a very narrow range (0.98-2.24, coefficient of variation = 24%). The mean and range of clonogenic cell fraction were found to be in agreement with published values of soft agar colony forming efficiencies in both murine and human tumors. However, further investigation is necessary to determine how accurately this method measures the relative clonogenic cell content in human tumors. Clinical correlations between clonogenic cell fraction values and the response to radiotherapy are still too early to determine. PMID- 1869462 TI - Should tumors be clamped in radiobiological fractionation experiments? AB - In radiobiological fractionation experiments tumors are often clamped during irradiation. This is done not only to facilitate the interpretation of the data by eliminating the influence of reoxygenation but also to avoid uncontrolled changes in the hypoxic fraction that are caused by anesthesia or stress from physical restraint. In this study it is shown that clamping of tumors during irradiation also affects repair, repopulation, and redistribution. From these results it is concluded that clamping of tumors during fractionated irradiation treatment does not appear to be an adequate measure to elucidate the mechanisms that determine tumor response to radiotherapy. Even some of the fundamental concepts of tumor radiobiology might contain some uncertainties, since they are often based on data resulting from clamped tumors. PMID- 1869461 TI - Tumors growing in irradiated tissue: oxygenation, metabolic state, and pH. AB - Experimental tumors growing in irradiated tissue have been used to study the biological differences characteristic of locally recurrent tumors. Animal tumors were early generation isotransplants of a spontaneous fibrosarcoma in a C3Hf/Sed mouse, designated FSa-II. Since the hypoxic cell fraction of tumors growing in irradiated tissue is increased, these tumors are assumed to be metabolically deprived with hypoperfusion and acidosis. In this study we directly measured the oxygen partial pressure (pO2) distribution, metabolic state, and pH of tumors growing in an irradiated tumor bed using oxygen sensitive electrodes and 31P-NMR. The results confirmed a three-fold increase in the number of pO2 readings less than or equal to 2.5 mmHg and also showed increased acidosis with a 0.17 unit decrease in pHNMR. When tumors growing in pre-irradiated tissue reached approximately 100 mm3 in volume, a high frequency of gross and microscopic necrosis and hemorrhage was already observed. Consistent with these observations, the phosphocreatine/inorganic phosphate (PCr/Pi) and nucleoside triphosphate/inorganic phosphate (NTP/Pi) ratios were significantly lower in the tumors in a pre-irradiated bed compared to tumors in a non-irradiated bed (PCr/Pi: 0.51 vs 0.79, p less than 0.05; and NTP/Pi: 0.64 vs 0.93, p less than 0.05). The longitudinal relaxation time (T1) of Pi was numerically shorter in control tumors (consistent with the better tissue oxygenation), but this did not reach statistical significance (2.09 +/- .11 sec vs 2.25 +/- .16 sec). PMID- 1869463 TI - Dose in bone and tissue near bone-tissue interface from electron beam. AB - This work has quantitatively studied the variation of dose both within bone and in unit density tissue near bone-tissue interfaces. Dose upstream of a bone tissue interface is increased because of an increase in the backscattered electrons from the bone. The magnitude of this effect was measured using a thin parallel-plate ionization chamber upstream of a polymethyl methacrylate (PMMA) hard bone interface. The electron backscatter factor (EBF) increased rapidly with bone thickness until a full EBF was achieved. This occurred at approximately 3.5 mm at 2 MeV and 6 mm at 13.1 MeV. The full EBF at the interface ranged from approximately 1.018 at 13.1 MeV to 1.05 at 2 MeV. It was also observed that the EBF had a dependence on the energy spectrum at the interface. The penetration of the backscattered electrons in the upstream direction of PMMA was also measured. The dose penetration fell off rapidly in the upstream direction of the interface. Dose enhancement to unit density tissue in bone was measured for an electron beam by placing thermoluminescent dosimeters (TLDs) in a PMMA-bone-PMMA phantom. The maximum dose enhancement in bone was approximately 7% of the maximum dose in water. However, the pencil-beam algorithm of Hogstrom et al. predicted an increase of only 1%, primarily owing to the inverse-square correction. Film was also used to measure the dose enhancement in bone. The film plane was aligned either perpendicular or parallel to the central axis of the beam. The film data indicated that the maximum dose enhancement in bone was approximately 8% for the former film alignment (which was similarly predicted by the TLD measurements) and 13% for the latter film alignment. These results confirm that the X ray film is not suitable to be irritated "edge on" in an inhomogeneous phantom without making perturbation corrections resulting from the film acting as a long narrow inhomogeneous cavity within the bone. In addition, the results give the radiotherapist a basis for clinical judgment when electron beams are used to treat lesions behind bone or near bony structures. We feel these data enhance the ability to recognize the shortcomings of the current dose calculation algorithm used clinically. PMID- 1869464 TI - Concomitant chemotherapy-radiation therapy followed by hyperfractionated radiation therapy for advanced unresectable head and neck cancer. AB - In January 1988, we initiated a prospective study evaluating a new treatment approach with chemotherapy and radiotherapy for unresectable head and neck cancer. Weeks 1-4 were the initial debulking phase. Radiotherapy was delivered using 1.8 Gy/day to large portals including gross disease and all areas at risk. Cisplatinum, 100mg/m2, was given concomitant with radiotherapy on days 1 and 22. Weeks 5 and 6 were the boosting phase. This involved twice-a-day irradiation. The AM fraction of 1.8 Gy was given to the entire area at risk, whereas the PM dose of 1.6 Gy was limited to the gross disease alone. Thus a total of 70 Gy/6 weeks was delivered. A total of 24 patients were treated, 22 of whom have completed this protocol and are evaluable. All patients had massive disease, with 15 having gross involvement of brain, orbit, skull base, or carotid artery. Follow-up ranged from 3-22 months (median 12 months). Major responses were achieved in 96%, with 64% complete responses and 32% partial responses. Two patients with PR were able to undergo complete surgical resection, making the overall rate of complete response, including surgery, 73%. At 1 year, actuarial survival was 69%, and local progression-free survival was 56%. Distant metastases developed in 5 (23%). This approach appears both safe and effective in producing excellent regression and local control for far advanced head and neck cancer. More time is needed to see if these results are sustained. Efforts to build upon this experience appear warranted. PMID- 1869465 TI - Sensori-neural hearing loss in patients treated with irradiation for nasopharyngeal carcinoma. AB - The present investigation has been carried out to evaluate the sensitivity of the inner ear to irradiation. Cochlear function was tested in a cohort of 22 patients before and 7-84 months after receiving external irradiation for nasopharyngeal carcinoma. The pre-irradiation sensori-neural hearing threshold at 500, 1000, 2000, and 4000 Hz was used as a baseline for the individual patient, and the observed sensori-neural hearing loss (SNHL) was calculated as the difference between pre- and post-irradiation values. The pre-irradiation hearing level or patient age was not correlated with the actual SNHL. In contrast, there was a significant correlation between the total radiation dose to the inner ear and the observed hearing impairment. SNHL was most pronounced in the high frequencies, with values up to 35 dB (4000 Hz) and 25 dB (2000 Hz) in some patients. The latent period for the complication appeared to be 12 months or more. The deleterious effect of irradiation on the hearing should be kept in mind both in treatment planning and in the follow-up after radiotherapy. PMID- 1869466 TI - Radiotherapy for large symptomatic hemangiomas. AB - Between 1974 and 1988, 13 patients presented with large (3 to greater than 20 cm) symptomatic unresectable or partially resected hemangiomas. Tumor sites were extremities (five cases), vertebral bodies (three cases), face (two cases), pituitary fossa (one case), pelvic bones (one case), and bladder (one case). Symptoms included severe pain in eight patients, inability to use an extremity in five, vision problems in three, weakness in two, and hematuria with decreased urinary stream in one. Many patients had more than one symptom. Two of the cases were associated with life-threatening consumptive coagulopathies (Kasabach Merritt syndrome). Therapy was delivered with both orthovoltage and megavoltage photons. Doses ranged from 6.25 to 40.0 Gy in 1.6- to 2.5-Gy fractions. Follow-up ranged from 2 to 15 years (median, 13 years). Tumor shrinkage was noted in 9 (82%) of the 11 cases in which tumor size data were collected before and after therapy. Complete response of tumor mass occurred in 4 (36%) of 11, partial response occurred in 5 (45%), and no response occurred in 2 (18%). No tumor grew after radiotherapy. Some relief in symptoms occurred in all 13 patients; 10 (77%) had complete resolution of symptoms. In both patients with life-threatening cytopenias, hematologic values returned to normal after treatment. Because the majority of the patients responded to all dose levels administered, no firm dose response relationship was evident. However, objective (measurable) complete responses occurred in two (50%) of the four patients receiving doses of 30 Gy or greater compared with only two (29%) of the seven patients who received lesser doses. No long-term morbidity occurred. Radiotherapy of large unresectable and partially resected hemangiomas yields long-term relief of symptoms and tumor shrinkage in the majority of patients treated. PMID- 1869467 TI - Quality assurance in stereotactic radiosurgery using a standard linear accelerator. AB - Methods have recently been developed for using standard linear accelerators to perform stereotactic radiosurgery. The accuracy necessary to perform this procedure requires an intensive quality assurance program to encompass all aspects of dose calibration and mechanical integrity of the treatment unit, the treatment planning process, and treatment delivery. The programs developed at the Joint Center for Radiation Therapy (JCRT) include testing of the linear accelerator and the stereotactic system, cross checking of the treatment planning process, and a quality assurance check list of the treatment delivery procedure. This report outlines in detail the quality assurance program currently in use at the JCRT. PMID- 1869468 TI - Fractionated radiotherapy of small inoperable lesions of the brain using a non invasive stereotactic frame. AB - Arteriovenous malformations (AVMs) and benign or low grade, small malignant tumors can be treated by stereotactic radiotherapy in a single fraction. This report describes a technique for stereotactic treatment of small lesions using conventional, fractionated, photon beam irradiation. The Laitinen's stereoadapter, non-invasive head frame was used. This device was tested for accuracy by serial mountings and found to be accurate within 1 mm. The accuracy of the dose delivered was within 2%. Adaptation of this device to the linear accelerator required the design of secondary circular collimators which decreased the penumbra from 3-4 mm to 2-3 mm. The dose fall off outside the target volume is steep enough when using two non-coplanar arcs (90 to 10% within 1 cm). Thermoluminescent dosimetry (TLD) in a humanoid phantom showed good correlation with the calculated dose. This system permits delivery of fractionated radiation therapy to small volumes, easily and accurately, under stereotactic conditions. PMID- 1869470 TI - Prediction of Saturne II+ 10 MV and 23 MV photon beam output factors. AB - A two-variable, three-parameter formula for modified, virtual equivalent square sides has been worked out which, when incorporated into empirical output-square field size function, generates output values of rectangular fields taking into account the asymmetry of the collimating system of the Saturne II+ accelerator generating 10 MV and 23 MV photon beams. PMID- 1869469 TI - A comparison of postoperative techniques for carcinomas of the larynx and hypopharynx using 3-D dose distributions. AB - If a head and neck cancer originates low in the neck with a primary site below the shoulders, a technical challenge to the radiation oncologist exists in that the entire neck needs treatment while avoiding overlap of multiple fields on the spinal cord. No standard solution to this problem exists. We have developed a 3-D treatment planning tool that can be used to develop and compare 3-D treatment plans and dose distributions. Using this tool, we have studied the following techniques for the postoperative treatment of carcinomas of the larynx and hypopharynx, tumors that often embody the problems discussed above: (a) the mini mantle technique used at the Massachussetts General Hospital, (b) a 3-field technique used at the University of Florida at Gainesville (UF 3-field), (c) a 3 field technique used at our institution and at many others (standard 3-field), and (d) the kicked out lateral technique used at our institution and at others. The 3-D dose distributions from these plans are compared. With 100% delivered just anterior to the vertebral body at mid-neck, the mini-mantle technique results in large 120% hot spots laterally and anteriorly in the neck. Near the mastoid tips, however, the dose falls to 100%. The upper neck nodes may be underdosed since this is 20% cooler than the lateral-anterior neck dose (where a large 120% hot spot exists). The spinal cord is adequately blocked. The two 3 field techniques result in small hot spots at the junction of the lateral and anterior fields. Because different methods are used to prevent overlap at the spinal cord, these hot spots occur anteriorly in the standard 3-field technique and laterally in the UF 3-field technique. The spinal cord block results in untreated neck tissue which can be supplemented with electrons in the standard 3 field technique, but is left untreated in the UF 3-field technique. Both techniques result in a generous length of spinal cord which does not receive full dose. The kicked out lateral technique treats the entire neck and reconstructed pharynx without matching fields at midneck. The upper mid mediastinum is underdosed 10-20% despite being within the posterior inferior portion of the beam. This could be minimized by using a tissue compensator. Unless there is significant subglottic extension or significant risk of disease in the upper mediastinum, we favor treating these malignancies with the kicked out lateral technique, which avoids the problem of junctioning lateral and anterior fields and provides a fairly homogeneous dose distribution. PMID- 1869471 TI - The biological basis for conformal three-dimensional radiation therapy. AB - The recent introduction of new computer technology for treatment planning and computer-driven treatment delivery systems, such as multi-leaf collimators and on line verification systems, has accelerated the development of 3-dimensional (3-D) radiation therapy as a modality for curative cancer treatment. The goal of 3-D treatment planning is to conform the spatial distribution of the high radiation dose to the shape of the tumor contour while concomitantly decreasing the volume of the surrounding normal tissues receiving high radiation doses. The improved precision of tumor coverage and the exclusion of normal tissues should permit tumor dose escalation and may enhance local tumor control. It has been suggested that any survival gains derived from improvements in local control may be offset by the subsequent appearance of distant metastases arising from micrometastases already present at the time of initial diagnosis. However, clinical and laboratory studies indicate that failure to control the primary tumor at the time of initial treatment significantly increases the incidence of metastatic dissemination. This phenomenon is consistent with the hypothesis that the enhanced mitotic activity associated with the re-growth process of locally recurring primary tumors promotes the multi-step transformation of non-metastatic tumor cells into clonogens with metastatic potential, leading to increased overall rates of metastatic disease. These biologic considerations provide support for the need to focus attention on the identification of more effective therapeutic strategies designed to eradicate the primary local tumor completely at the time of initial therapy and serve as the rationale for clinical studies using 3-D conformal radiation therapy. PMID- 1869472 TI - Fractionated regimens for stereotactic radiotherapy of recurrent tumors in the brain. AB - Radiosurgery (single-fraction stereotactic radiotherapy) was initially developed to treat non-malignant arteriovenous malformations, but there is growing interest in its use for the treatment of recurrent brain tumors. We suggest that there are sound reasons to expect improved results for tumor radiotherapy, in terms of late effects, if a fractionated regimen is used. At present, no published guidelines are available for choosing appropriate doses for fractionated regimens. We present two sets of guidelines, based on experimentally derived radiobiological parameters: first, we estimate gamma-ray doses which, if delivered in various numbers of fractions, should produce equivalent early effects to 70 Gy of 125I X rays delivered at low dose rate; this latter regimen is currently used in RTOG interstitial brachytherapy trials. Second, we estimate doses for multi-fractioned stereotactic radiotherapy which may be advantageous alternatives to particular doses of single-fractioned radiosurgical therapy. As the appropriate hardware is available, the use of fractionated stereotactic radiotherapy deserves serious consideration for the treatment of recurrent tumors in the brain. PMID- 1869473 TI - Development of scanned focussed ultrasound hyperthermia: clinical response evaluation. AB - Selective heating of irregularly shaped tumors at depth can now be accomplished through focussing and controlled scanning of energy deposition patterns by ultrasound. A scanned focussed ultrasound (SFUS) hyperthermia system developed at the University of Arizona has been used to deliver 220 treatments to 87 tumors in 71 patients with extracranial malignancies between October 1986 and May 1990. Patients received an average of three SFUS hyperthermia treatments, spaced weekly, during ongoing fractionated radiotherapy. The most common anatomic sites treated were the pelvis (22 patients), chest wall or breast (14), neck (8), and axilla (7), while the most common histologies were adenocarcinoma (36), squamous cell carcinoma (11), and melanoma (10). Concurrent radiotherapy was delivered (range 1000-7640 cGy, mean 4320 cGy) to 67 SFUS hyperthermia patients; 4 received concomitant chemotherapy. Tumor volumes ranged from 1-2100 cubic centimeters (mean 325 cc), and 75% were located at depths greater than 3 cm from skin. A 62% overall response rate was observed, with 22% of treated tumors demonstrating a complete response (defined as complete disappearance of treated tumor), and 40% exhibiting a partial response (defined as greater than or equal to 50% reduction in tumor volume). Dramatic local pain reduction was achieved in 42% of the tumors treated. The acute tolerance of SFUS hyperthermia was quite good, and chronic toxicities (persistent skin blisters/burns) were identified in two patients. The versatility of the SFUS system is discussed, as well as its future potential for improving control of advanced loco-regional malignancies treated with curative intent. PMID- 1869474 TI - CNS imaging of neoplasms. PMID- 1869475 TI - Current applications of imaging procedures in the patient with lung cancer. AB - The primary role of imaging procedures in the patient with lung cancer should be focused on staging and follow-up challenges. The role of imaging procedures in the detection of the patient at risk for primary lung cancer remains limited and cannot be recommended at present. There is no significant difference between the yield of CT and MR in this patient group, with the possible exception of a more specific role for MR when questions are raised concerning hilar lymph node involvement and mediastinal compartmental invasion. The main role of cross sectional imaging techniques should be in the avoidance of unnecessary surgical procedures, identifying the unresectable patient prior to exploratory thoracotomy. It should be emphasized that all radiographic abnormalities are non specific and must be histologically verified before presuming that an abnormal lymph node or large adrenal gland contains metastatic lung cancer. PMID- 1869476 TI - Three-dimensional conformal radiation therapy: a testable hypothesis. PMID- 1869477 TI - Interstitial therapy in the management of early stage carcinomas of oral cavity. PMID- 1869478 TI - Choosing a maximum spinal cord dose. PMID- 1869479 TI - 192 iridium implantation of base of tongue carcinoma. PMID- 1869480 TI - Response to Goffinet, Harrison, Puthawala, and Syed. PMID- 1869482 TI - Bovine cell lines for collaborative gene mapping studies. PMID- 1869481 TI - Glucocorticoids increase myoblast proliferation rates by inhibiting death of cycling cells. PMID- 1869483 TI - Sequence of rat keratinocyte growth factor (heparin-binding growth factor type 7) PMID- 1869484 TI - Identification of bovine serum albumins that support salmonid cell proliferation in the absence of serum. PMID- 1869485 TI - Growth of neonatal rat uterine luminal epithelium on extracellular matrix. AB - We have developed a tissue culture system using an extract of basement membrane (extracellular matrix) which promotes the in vitro growth and development of uterine luminal epithelium from the 5-day-old rat. Uterine luminal epithelium, free of stroma, was obtained as short tubes by trypsinization of uterine segments followed by mechanical separation. Epithelial segments were grown in a serum-free medium on culture dishes coated with an extracellular matrix. After 2 days, rapid cell growth resulted in monolayer cultures, which subsequently formed organoid structures similar to differentiated uterine glands present in uterine tissue taken from older rats. Electron microscopy of cultures revealed columnar cells with basally located nuclei, apical microvilli, lateral membranes with interdigitations, desmosomes, and secretory Golgi complexes, all features found in functioning uterine epithelium in vivo. This model will allow the in vitro investigation of the development of uterine epithelium-specific functions free of the influence of stromal cell factors. PMID- 1869486 TI - Fibroblastlike primary cells from human colon adenocarcinoma explants: collagen biosynthesis. AB - Fibroblastlike primary cells have been obtained from human colon adenocarcinoma explants. Such cells disappear during cell culture and thus have not been previously studied. These cells have a number of altered phenotypic characteristics: a) morphology; b) growth behavior and adherence to culture substrate (they required 3 h for 90% attachment and only presented a flattened morphology 40 h after platting); and c) collagen metabolism. Increased protein biosynthesis (about double than control colon-derived fibroblasts) and maintained ability for collagen biosynthesis have been observed for the tumor-associated fibroblastlike cells. Thus, the collagen to noncollagenous proteins ratio was decreased for these cells. They exhibited an altered type I:type III collagen (5:1 instead of 3:1 in colon fibroblasts) and procollagen (2:1 against 5:1 in colon fibroblasts) ratios as well as a decreased secretion of collagen with an abnormal deposition of procollagens in the cell layer. These studies show a permanent phenotypic alteration in the tumor-associated fibroblast-like cells. PMID- 1869487 TI - Proliferation and differentiation of prepubertal mouse vaginal epithelial cells in vitro and the specificity of estrogen-induced growth retardation. AB - Mouse vaginal epithelial cells were isolated from intact 21-day-old BALB/cCrgl mice and cultured in a serum-free medium (SF20: basal medium supplemented with insulin, epidermal growth factor, transferrin, and bovine serum albumin--fraction V) to examine the proliferation, differentiation, and specificity of estrogen induced growth retardation in vitro. Histologic and ultrastructural studies showed that vaginal epithelial cells undergo differentiative changes in vitro in the absence of estrogen, and that these changes are similar to those induced in vivo by estrogen. Addition of 17 beta-estradiol inhibited cellular proliferation in a dose-dependent manner. Whereas other estrane derivatives (17 alpha-estradiol and estriol) also significantly retarded cellular proliferation, cholesterol, testosterone, and progesterone had no effect. Keoxifene, an antiestrogen, significantly reversed estrogen-induced growth inhibition, resulting in proliferation of estrogen-treated cells equivalent to that of the untreated control. The results suggest that both proliferation and differentiation of prepubertal mouse vaginal epithelial cells in vitro are estrogen-independent, and that the growth inhibition is a specific estrogen-induced response. PMID- 1869488 TI - Replacement of vertebrate serum with lipids and other factors in the culture of invertebrate cells, tissues, parasites, and pathogens. AB - Culture medium supplementation with vertebrate serum results in the selection of fibroblastoid insect cell lines and a general decline during continuous subculturing of both morphologic and functional differentiation of the surviving cells. Essential lipid mixtures can substitute for vertebrate serum in the culture of insect and some vertebrate cells, tissues, parasites, and pathogens. The provision of sterols and essential (with nonessential) polyunsaturated fatty acids as phospholipids in oxidation-protected peptoliposomes or proteoliposomes allows cells in culture to duplicate in vivo specific membranes more accurately. Such lipid-corrected membranes allow cultured cells to communicate with neighboring cells through the extracellular matrix, effectively transmit hormonal signals directly and via receptor control, and respond with various tissue specific functions and differentiation states as directed. PMID- 1869489 TI - Insect tissue culture systems: models for study of hormonal control of development. AB - The regulation of growth and development of insects is under endocrine control and involves both juvenile hormones and ecdysteroids. Neuropeptides are master regulators which control the secretion of these hormones. Most experiments in insect endocrinology have been conducted in vivo, but tissue culture methodology is playing an increasing role due to the great interest in simpler model systems for the study of complex processes that occur in vivo. The availability of appropriate media has allowed the culture of a variety of insect organs and cell lines of defined origin which have kept certain properties of the parent tissues. Tissue culture approaches have been useful for studying hormonal control of morphogenetic processes. Cell lines are particularly suited to the study of hormonally regulated mechanisms of macromolecular biosynthesis and gene expression. Thus, the value of in vitro analysis in studies of regulation of hormone production is now recognized. Results obtained from tissue culture allow more precise definition of the hormonal requirements of insect cells and tissues for growth and differentiation and might make possible the discovery of new growth regulators. PMID- 1869490 TI - Growth factors in invertebrate in vitro culture. AB - An increasing number of polypeptide growth factors have been identified that have proven essential in the development of defined cell culture media for mammalian cell culture. The development of defined mammalian cell culture media, in turn, has provided an environment for studying cell lines in an experimentally manageable unit for studying the action of cellular regulators and genes that determine the properties of cells. Evidence that vertebrate growth factors may be present in insects is based on DNA sequences that encode epidermal growth factor and transforming growth factor-beta. However, research on the influence of commercially available vertebrate growth factors is very limited. Although the majority of insect growth-promoting substances studied were isolated directly from insect hemolymph, few of these have been purified to the extent that they could be tested in insect cell, tissue, and endoparasite cultures. Research is needed in both of these areas to aid in developing defined insect culture systems, and to understand better the regulation of postembryonic growth and development in insects. PMID- 1869491 TI - Hormonal effects on insects and other endoparasites in vitro. AB - Metamorphic and reproductive events in vertebrates and invertebrates are under endocrine control and are often correlated with developmental, behavioral, or reproductive changes in the parasites living in or on these hosts. This paper reviews selected examples of a) host hormone mediated influences on endoparasites in vivo, b) host hormone effects in vitro on protozoan, helminth, and insect endoparasites, and c) identifies possible relationships in hormone effects across parasite taxa. The significance of studies on endoparasites in vitro in relation to the impact of host hormones, antihelminthic, and prophylactic drugs on parasite growth and proliferation will also be addressed. A review of the literature indicates only limited studies have been done in vitro in an attempt to elucidate the bases of reported host hormone influences on endoparasites in vivo. Steroid hormones of hosts seem to stimulate growth, molting or encystment or both of helminth, insect, and protozoan parasites. Vertebrate steroids such as estrogen, testosterone, and progesterone had primarily reproduction- or growth promoting effects or both on protozoan and nematode parasites. Insect ecdysteroids such as ecdysone, 20-hydroxyecdysone, and makisterone were the most widely studied steroids in vitro and induced growth or molting or both of cestode, nematode, and insect parasite larvae. Although juvenile hormone (JH III) stimulated growth in the protozoan and nematode parasites tested, the analogue methoprene and JH precursors, farnesal, farnesol, and farnesol methyl ether had various effects. Biogenic amines also varied in their effects on the nematode parasites tested, while the peptide hormone, insulin, stimulated growth in the protozoans tested. The evidence for in vitro effects of host hormones on their natural endoparasites is patchy at best. Additional studies are needed to identify the biochemical bases for the numerous host hormone mediated effects on parasites. PMID- 1869492 TI - Physiologic studies of snail-schistosome interactions and potential for improvement of in vitro culture of schistosomes. AB - Despite extensive efforts to develop suitable media for rearing the intramolluscan stages of schistosomes, successful in vitro culture of these parasites remains elusive. Recent 31P NMR studies demonstrated that the levels of free phospholipids, particularly phosphatidylcholine, in the digestive gland of the snail, Biomphalaria glabrata, were dramatically reduced when the host was infected with Schistosoma mansoni. It was speculated that absorption of host phosphatides may be an important source of membrane phospholipid precursors and fatty acids for developing sporocysts and cercariae. During the present investigations, B. glabrata was maintained on a high fat diet of egg yolk, and the lipid composition of control uninfected and infected snails examined by 31P and 13C NMR. In addition, the levels of host hemolymph metabolites, including glucose and urea, considered as indicators of parasite nutrient uptake, were monitored. The lipid level of snails fed egg yolk was greatly increased, and hosts developed patient infections in approximately half the time of infected snails maintained on lettuce. The composition of the free phospholipids accumulated in the tissues of B. glabrata fed egg yolk were the same as those previously reported in the cercarial stage of S. mansoni. Moreover, the fatty acids of S. mansoni and those reported here in the neutral lipids and free phosphatides in the host tissues were similar. Uninfected snails maintained on lettuce had higher hemolymph levels of glucose than those reared on egg yolk, and infected hosts on egg yolk had significantly lower levels of hemolymph urea. Beta hydroxybutyrate was the principal hemolymph metabolite in snails fed egg yolk, but was not detected in snails maintained on lettuce.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869493 TI - Perspectives on the in vitro culture of filariae. AB - A primary constraint in the culture of human filariae is in obtaining starting material--either microfilariae (mfs), which infect invertebrates, or third stage larvae (L3s), which are infective to humans. Cryopreservation methods which partially overcome this difficulty have been developed for both mfs and L3s. Complete development of mfs to L3s outside an intact host was obtained recently when mosquito thoraces infected by Brugia malayi (24 h after the bloodmeal) were maintained in vitro. In another recent study in which no host tissues were present, a semidefined culture medium was used to investigate the properties of reduced glutathione (GSH) that stimulate early development of Onchocerca lienalis mfs. An extended cysteinyl backbone and a free sulfhydryl were identified as the key structural elements provided by GSH. Stimulation also required the presence of low and high molecular weight components of serum as well as oxygen. Molting of Onchocerca spp. L3s to the fourth stage at the rate of 50 to 70% has been reported by several researchers. Key factors identified in those successes have been temperature and serum lot. Improved long-term viability occurred with cellular co-culture. Beneficial effects of co-culture were shown to be due both to cellular conditioning of the medium as well as to lowered dissolved oxygen levels as a result of cellular metabolism. With the use of cell-conditioned medium and decreased incubator oxygen levels, long-term viability of Onchocerca larvae in culture exceeded that previously reported. Recently, Brugia malayi adults of both sexes were cultured from L3s using a semidefined medium supplemented with human serum. Many of these sexually matured adults mated and produced viable microfilariae. PMID- 1869494 TI - Elimination of mycoplasmas from cell cultures by a novel soft agar technique. AB - Mycoplasmal infection of cell cultures remains a significant threat to diagnostic and research procedures. In certain defined situations, curing of mycoplasmal infected cultures is a reasonable exercise. Four methods of curing were compared: treatment with BM-cycline, 5 bromouracil, use of specific antisera and treatment of infected cells suspended in soft agar with antibiotics. Antisera treatments were of low efficiency of curing: 50%. None of nine infected cell lines treated with 5-bromouracil were consistently cured of mycoplasmas. The use of BM-cycline was effective for some, but not all lines and required long periods of treatment, 12-21 days. 35 naturally or deliberately infected cultures were treated in soft agar a total of 119 times. This procedure which consisted of suspending infected cultures in soft agar containing appropriate antibiotics resulted in successful mycoplasmal elimination 118/119 times. This soft agar technique took 1-3 days. In separate studies, it was shown that certain Mycoplasma fermentans strains were resisted to this and other curing methods. This may be due to their intracellular location. Such strains may be more amenable to antibiotics that penetrate mammalian cells. It is concluded that the soft agar technique is a rapid, efficient and reliable method to eliminate cell culture mycoplasmas. PMID- 1869495 TI - Bright light augmentation in antidepressant nonresponders. AB - BACKGROUND: This study was designed to examine the potential benefit of the addition of bright lights to antidepressant treatment in depressed subjects. METHOD: Ten patients who presented during the winter months with major depression and who had failed an adequate trial of antidepressants or who had relapsed following a successful course of antidepressants underwent a 2-week course of bright light therapy. RESULTS: Augmentation with bright lights resulted in substantial improvement in 7 of the 10 patients. CONCLUSION: Bright light augmentation may provide a useful treatment alternative for patients with treatment-resistant depression. PMID- 1869496 TI - Is doxepin a safer tricyclic for the heart? AB - BACKGROUND: Many clinicians believe that doxepin is the safest tricyclic with respect to cardiovascular effects. This belief has persisted for two decades despite the absence of rigorous prospective evaluation. METHOD: To address this issue, the authors studied the cardiovascular effects of doxepin in 32 depressed patients with preexisting left ventricular impairment, ventricular arrhythmias, and/or conduction disease. RESULTS: Doxepin (1) did not have a robust effect on heart rate, (2) did not adversely affect left ventricular function, (3) did have a significant antiarrhythmic effect, (4) slowed cardiac conduction, and (5) caused a significant increase in orthostatic hypotension. Five (16%) of the 32 patients dropped out due to cardiovascular side effects. The overall dropout rate was 41%. CONCLUSIONS: The cardiovascular effects of doxepin in depressed patients with heart disease are comparable to those documented for imipramine and nortriptyline. Doxepin afforded no greater margin of cardiovascular safety; in fact, the drug was poorly tolerated by this patient population. PMID- 1869498 TI - Phototherapeutic response variability in seasonal affective disorder. PMID- 1869497 TI - Comparison of withdrawal of typical and atypical antipsychotic drugs: a case study. AB - Haloperidol and clozapine were rapidly withdrawn from a schizophrenic patient on separate occasions several months apart. Mental status changes and fluctuations in involuntary movements were carefully observed under both conditions. Although little change in either mental status or involuntary movements was observed within the 3 weeks following the withdrawal of haloperidol, marked deterioration in mental status and involuntary movements occurred within 1 week of withdrawal of clozapine. Implications of this differential response to withdrawal of antipsychotic medications are discussed. PMID- 1869499 TI - Prolonged cocaine psychosis implies underlying major psychopathology. PMID- 1869500 TI - More on the effects of monosodium glutamate. PMID- 1869501 TI - Is the tendency to weep one of the most useful indicators for depressed mood? PMID- 1869502 TI - Cerebral infarct presenting as mania. PMID- 1869503 TI - 9-(Dicyanovinyl)julolidine binding to bovine brain calmodulin. AB - A molecular rotor, 9-(dicyanovinyl)julolidine (DCVJ), is a fluorescent dye whose intramolecular rotation determines its fluorescence yield [Kung, C.E. & Reed, J.K. (1989) Biochemistry 28, 6678-6686]. DCVJ binds to bovine brain calmodulin and emits strong fluorescence. In fluorescence titration experiments, the dissociation constant and the number of binding sites were determined to be 20 +/ 10 microM and 0.7 +/- 0.5 in the presence of Ca2+, and 22 +/- 10 microM and 0.6 +/- 0.5 in the absence of Ca2+, respectively. The fluorescence intensity of bound DCVJ increased 10-fold in the presence of Ca2+ compared to that in the absence of Ca2+. The fluorescence titration curve of DCVJ-calmodulin showed a transition at pCa 6.5. Over the same Ca2+ range, a decrease in molecular ellipticity at 222 nm and an increase in tyrosine fluorescence of calmodulin were observed. These results mean that the conformational change of calmodulin due to the Ca2+ binding induces the microenvironmental change of the DCVJ binding site from the flexible to the rigid state, resulting in inhibition of the intramolecular rotation of DCVJ and an increase in its fluorescence. PMID- 1869504 TI - A micro method involving micro high-performance liquid chromatography-mass spectrometry for the structural characterization of neutral glycosphingolipids and monosialogangliosides. AB - A micro method involving high-performance liquid chromatography-fast atom bombardment mass spectrometry (HPLC/FAB/MS) has been developed for the sensitive structural characterization of neutral glycosphingolipids and monosialogangliosides. The method involves a micro silica gel column (0.3 mm i.d. x 100 mm) and a micro HPLC apparatus working at a flow rate of 6 microliters/min. All injected materials can be structurally characterized by mass spectrometry without the splitting or wasting of materials, which was not possible with our previous method [M. Suzuki et al. (1990) J. Biochem. 108, 92-98]. A mixture containing 160 ng each of five neutral glycosphingolipids (GlcCer, LacCer, Gb3Cer, Gb4Cer, and IV3 alpha GalNAc-Gb4Cer) and a mixture containing 160 ng each of three monosialogangliosides [GM3(NeuAc), GM2(NeuAc), and GM1(NeuAc)] were injected into the micro HPLC with programmed elution with isopropanol-n-hexane water with or without ammonium hydroxide. Each glycosphingolipid was separated by mass chromatography and the obtained mass spectra were suitable for structural characterization. Thus, the characterization of glycosphingolipids was achieved with small amounts of materials, 160 ng each, and in mixtures. PMID- 1869505 TI - Characterization of beta-D-xyloside-induced glycosaminoglycans and oligosaccharides in cultured human skin fibroblasts. AB - Human skin fibroblasts were incubated in the presence of a fluorogenic xyloside, 4-methylumbelliferyl beta-D-xyloside. Three fluorogenic components were isolated and purified from the culture medium by gel permeation high-performance liquid chromatography. Their structures were then characterized by enzymatic digestion, fast-atom-bombardment mass spectrometry, gas-liquid chromatography, and electrophoresis on cellulose acetate membrane. The results showed that one of the components was a mixture of dermatan sulfate (70%) and chondroitin sulfate (30%), bearing the 4-methylumbelliferone at the reducing termini, and having an average molecular weight of 9,200. The others had the structures galactosyl-galactosyl xylosyl-4-methylumbelliferone and galactosyl-xylosyl-4-methylumbelliferone, respectively, representing the linkage region between the glycosaminoglycan chains and core protein, except that 4-methylumbelliferone replaced the amino acid. Moreover, it was demonstrated that these oligosaccharides were intermediates of glycosaminoglycan synthesis, not depolymerized products. PMID- 1869506 TI - Heavy meromyosin induces sliding movements between antiparallel actin filaments. AB - Suzuki et al. [Biochemistry 28, 6513-6518 (1989)] have shown that, when F-actin is mixed with inert high polymer, a large number of actin filaments closely align in parallel with overlaps to form a long and thick bundle. The bundle may be designated non-polar, as the constituent filaments are random in polarity (Suzuki et al. 1989). I prepared non-polar bundles of F-actin using methylcellulose (MC) as the high polymer, exposed them to heavy meromyosin (HMM) in the presence of ATP under a light microscope, and followed their morphological changes in the continuous presence of MC. It was found that bundles several tens of micrometers long contracted to about one-third the initial length, while becoming thicker, in half a minute after exposure to HMM. Subsequently, each bundle was split longitudinally into several bundles in a stepwise manner, while the newly formed ones remained associated together at one of the two ends. The product, an aster like assembly of actin bundles, was morphologically quiescent; that is, individual bundles never contracted upon second exposure to HMM and ATP, although they were still longer than the F-actin used. Bundles in this state consisted of filaments with parallel polarity as examined by electron microscopy. This implies that non-polar bundles were transformed into assemblies of polar bundles with ATP hydrolysis by HMM. Importantly, myosin subfragment-1 caused neither contraction nor transformation. These results are interpreted as follows. In the presence of ATP, the two-headed HMM molecule was able to cross-bridge antiparallel actin filaments, as well as parallel ones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869507 TI - Microtubule-disrupting drugs blocked delivery of endocytosed transferrin to the cytocenter, but did not affect return of transferrin to plasma membrane. AB - The fluorescence of FL cells after endocytosis of rhodamine-labeled transferrin initially appeared as a dispersed punctate pattern over the whole cell and then accumulated in the cytocenter on further incubation. In nocodazole-treated cells, the punctate fluorescence appeared along the cell edges, and stayed there on further incubation but did not accumulate in the cytocenter. The localization of transferrin was examined at the electron microscopic level with horseradish peroxidase (HRP)-labeled transferrin. Nocodazole did not affect endosome formation but affected the distribution of the endosomes. Several types of endosomes (tubular, small spherical, and microvesicular endosomes) were observed in nocodazole-treated cells, as in control cells. The endosomes were in the Golgi area of the cytocenter and also in peripheral cytoplasm in control cells. In contrast, the endosomes were only in the periplasm, along the cell edges, in nocodazole-treated cells. The uptake and release of HRP-transferrin and the release of ferric ion into the cytoplasm in nocodazole-treated cells followed in the same time-course as those in control cells. The release of transferrin was the exponential with a half-time of 12 min. The activation energy of a rate limiting step in the recycling was 5.5 kcal.mol-1 at around 37 degrees C and increased to 29 kcal.mol-1 below 25 degrees C. These results indicated that microtubule-dependent endosome transport was faster than the overall recycling process and was independent of the return event of transferrin to the plasma membrane. PMID- 1869508 TI - Dynamics of the bilayer-water interface of phospholipid vesicles and the effect of cholesterol: a picosecond fluorescence anisotropy study. AB - The motion of the head group of phospholipid molecules in the bilayer structure was investigated by a picosecond fluorescence anisotropy technique using a newly synthesized fluorescent phospholipid, dipalmitoyl-L-alpha-phosphatidyl-(3-p methoxyphenyl)umbelliferone (DPPU). In this phospholipid, a coumarin derivative is attached covalently to the phosphate moiety. The motion of the acyl chain of the phospholipid was also investigated by the same method using 1-palmitoyl-2-(3 diphenylhexatrienyl)-propanoyl-L-alpha-phospha tid ylcholine (DPHpPC). From fluorescence anisotropy decay the wobbling diffusion rate (Dw) of DPPU and DPHpPC in DPPC vesicles at 45 degrees C was calculated to be 2.7 x 10(9) s-1 and 5.1 x 10(7) s-1 using the wobbling-in-cone-model. The range of the motion was calculated as the cone angle (theta c), which is half of the angle of the cone in which the fluorophore can diffuse. The cone angle of the coumarin skeleton of DPPU in DPPC vesicles at 45 degrees C was 64 degrees, which was larger than that of the DPH skeleton of DPHpPC, 40 degrees. These results indicate that the motion of the head group is much faster and wider than that of the acyl chain. When cholesterol was added to the DPPC vesicles, the range of motion of the acyl chain decreased, but that of the head group increased. These facts show that cholesterol restricts the motion of the acyl chain but enhances that of the head group in the phospholipid bilayer. PMID- 1869509 TI - Subsite structure of Saccharomycopsis alpha-amylase secreted from Saccharomyces cerevisiae. AB - The kinetic parameters (kcat/Km) and the cleaved-bond distributions for the hydrolysis of linear maltooligosaccharides Gn (3 less than or equal to n less than or equal to 9) by Saccharomycopsis alpha-amylase (Sfamy) secreted from Saccharomyces cerevisiae were determined at pH 5.25 and 25 degrees C. The subsite affinities of Sfamy were also evaluated from these data. The subsite structure of Sfamy is characteristic of the active site of an endo-cleavage type enzyme, consisting of internal repulsive sites with the catalytic residues and external attractive sites. Moreover, the pKa values of the catalytic residues were calculated from the pH dependence plot of the kinetic parameter (kcat/Km). The amino acid residues which contribute to the subsite affinities and the catalytic activity of Sfamy are proposed and compared with those of Taka-amylase A. PMID- 1869510 TI - Tyr225 in aspartate aminotransferase: contribution of the hydrogen bond between Tyr225 and coenzyme to the catalytic reaction. AB - Tyr225 in the active site of Escherichia coli aspartate aminotransferase (AspAT) was replaced by phenylalanine or arginine by site-directed mutagenesis. X-ray crystallographic analysis of Y225F AspAT showed that the benzene ring of Phe225 was situated at the same position as the phenol ring of Tyr225 in wild-type AspAT. The mutations resulted in a great decrease in the rate of the transamination reaction, suggesting that Tyr225 is important for efficient catalysis. The kinetic analysis of half-transamination reactions of Y225F AspAT with four substrates (aspartate, glutamate, oxalacetate, and 2-oxoglutarate) and some analogues (2-methylaspartate, succinate, and glutarate) revealed a considerable increase in the affinities for all these compounds. In contrast, affinity for the amino acid substrates was decreased by mutation to arginine, but affinities for the keto acid substrates and the two dicarboxylates (succinate and glutarate) were increased. The electrostatic interaction between O(3') of the coenzyme [pyridoxal 5'-phosphate (PLP)] and the residue at position 225 affected the pKa value of the Schiff base, which is formed between the epsilon-amino group of Lys258 and the aldehyde group of PLP; based on the spectrophotometric titration the pKa values were determined to be 6.8 for wild-type AspAT, 8.5 for Y225F AspAT, and 6.1 for Y225R AspAT in the absence of substrate. The absorption spectra of the three AspATs were almost identical in the acidic pH region, but the spectrum of Y225F AspAT differed from that of wild-type or Y225R AspAT in the alkaline pH region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869511 TI - 3-keto-5 alpha-steroid-delta 4-dehydrogenase from Nocardia corallina: purification and characterization. AB - The inducible 3-keto-5 alpha-steroid-delta 4-dehydrogenase of Nocardia corallina was purified to homogeneity using affinity chromatography on 19-nortestosterone 17-acetoxyaminoethyl Sepharose 4B. SDS-polyacrylamide gel electrophoresis, gel filtration and spectral analysis of flavin suggest that the purified dehydrogenase is a monomeric protein of Mr 60,000 containing one flavin. It has a typical absorption spectrum of flavoprotein with maxima at 457, 375, and 277 nm. The values shifted to 470 and 395 nm on binding of 19-nortestosterone. The enzyme catalyzed the dehydrogenation of 3-keto-5 alpha-steroid at the 4- and 5-position, e.g. the conversion of 5 alpha-androst-1-ene-3,17-dione to 1,4-androstadiene-3,17 dione with the reduction of phenazine methosulfate. The substrate 3-ketosteroid has essentially the 5 alpha-configuration. The enzyme did not reduce potassium ferricyanide but did reduce cytochrome c at a moderate rate, and exhibited only a weak steroid oxidase activity. Stereochemical study demonstrated that the enzyme abstracts the 4 beta, 5 alpha-hydrogens of the substrate as a hydrogen ion through a protein-based reaction and as a hydride ion by transfer to FAD, respectively. The enzyme oxidizes a wide variety of 3-keto-5 alpha-steroids but not 3 beta-hydroxysteroid. The dehydrogenase also catalyzed steroid transhydrogenation between 3-keto-5 alpha-steroid and 3-keto-1,4-diene-steroid. The properties of this enzyme are compared with those of 3-keto-steroid-delta 1 dehydrogenase. PMID- 1869512 TI - Protein rotation study of cytochrome P-450 in submitochondrial particles: effect of KCl and intermolecular interactions with redox partners. AB - The rotational diffusion of cytochrome P-450 in submitochondrial particles (SMP) of bovine adrenocortical mitochondria was measured by detecting the decay of absorption anisotropy, r(t), after photolysis of the heme.CO complex by a vertically polarized laser flash. Analysis of r(t) was based on a "rotation-about membrane normal" model. The measurements were used to investigate the effect of KCl on intermolecular interactions involving cytochrome P-450 and to investigate the interactions of cytochrome P-450 with other redox partners. The rotational diffusion of cytochrome P-450 was significantly dependent on KCl concentration. When the KCl concentration was increased from 0 to 1,000 mM, the mobile population of cytochrome P-450 was increased from 33 to 82%. After removing the KCl, the mobile population of cytochrome P-450 returned to the original 33%. These results suggest that nonspecific protein aggregates are dissociated by the presence of KCl, possibly due to the change in electrostatic interactions, resulting in mobilization of cytochrome P-450. SMP were observed to be nearly free from adrenodoxin and adrenodoxin reductase. The addition of adrenodoxin to SMP increased the mobile population of cytochrome P-450 from 35 to 54%. Further addition of adrenodoxin reductase to SMP containing adrenodoxin immobilized cytochrome P-450 by 6%. The addition of only adrenodoxin reductase to SMP, however, did not immobilize cytochrome P-450. The present results are consistent with our previous observations [Ohta, Y., Mitani, F., Ishimura, Y., Yanagibashi, K., Kawamura, M., & Kawato, S. (1990) J. Biochem. 107, 97-104] that cholesterol bearing P-450SCC forms a transient ternary association with adrenodoxin and adrenodoxin reductase. PMID- 1869513 TI - Determination of lectin-sugar binding constants by microequilibrium dialysis coupled with high performance liquid chromatography. AB - We used high performance liquid chromatography to determine the concentrations of free ligands after equilibrium dialysis to examine lectin-sugar interactions. The binding of p-nitrophenyl 1-thio-alpha-mannoside, p-nitrophenyl N-acetyl-1-thio beta-glucosaminide, and the pyridylamino derivative of Man6GlcNAc2 to concanavalin A and Triticum vulgaris lectin was examined. The binding constant, Ka, and the concentration of total binding sites, [L]t, were calculated from the trace amounts of sugars and lectins using the equation, [S]/[LS] = 1/Ka[L]t + [S]/[L]t, where [S] is the concentration of free ligand and [LS] the concentration of bound ligand. PMID- 1869514 TI - Conformational change of the foot protein of sarcoplasmic reticulum as an initial event of calcium release. AB - Heavy sarcoplasmic reticulum vesicles were labeled with the thiol-reacting fluorescent probe N-(7-dimethylamino-4-methyl-4-coumarinyl)maleimide (DACM), and the DACM-labeled foot protein moiety was purified. The fluorescence intensity of the DACM attached to the foot protein decreased by the addition of low (activating) concentrations of ryanodine, while it increased at higher (inhibitory) concentrations, suggesting that the lower fluorescence represents the active state of the foot protein, while the higher fluorescence, its inactive state. Under conditions that induce Ca2+ release from SR (Ca2+ jump, addition of Ca2+ release inducing reagents such as caffeine and polylysine), the fluorescence intensity of the protein-attached DACM decreased rapidly (e.g. k congruent to 70 s-1 under optimum conditions). The initial rate of Ca2+ release from the DACM labeled SR showed a close correlation with the amplitude of the fluorescence change of the foot protein-attached DACM under variety of conditions; e.g. in the presence of Ca2+, polylysine, ATP, and ruthenium red, etc. The fluorescence change of the foot protein was much faster than Ca2+ release from SR under a variety of conditions of Ca2+ release. We propose that the binding of release triggering reagents to the foot protein induces a rapid conformational change, which in turn regulates Ca2+ release. PMID- 1869515 TI - Evidence for the presence of a specific ganglioside GM1/valinomycin complex in mixed monolayers. AB - The effect of a negatively charged mono-sialoglyco-sphingolipid (GM1-ganglioside) on the molecular organization and on physiochemical properties of lipid/peptide (valinomycin) systems was investigated in monolayers at the air/water interface. At a high molar fraction of GM1, the surface pressure/area isotherms of the two component films of the system GM1/valinomycin and the isotherm of the pure ganglioside monolayer are identical concerning the space requirement of the molecules and thereby the packing of the monolayer. Using space-filling molecular models, a simple calculation gives the theoretical amount of 4.5 ganglioside molecules associated with one molecule of the depsipeptide valinomycin. The average surface potential indicates, that valinomycin, interacting with the polar head group of GM1, becomes partly embedded within the lipid interface. For GM1/eicosanol and valinomycin/eicosanol mixtures, the agreement between theory and experimental data strongly supports the model of ideal mixing without any molecular interactions between the different components. The results suggest the formation of a ganglioside/valinomycin complex with simultaneous alteration of the surface potential and molecular structure of the single components. PMID- 1869516 TI - Effect of acetylpolyamines on in vitro protein synthesis and on the growth of a polyamine-requiring mutant of Escherichia coli. AB - The functions of acetylpolyamines were examined with respect to stimulation of protein synthesis and cell growth. Unlike polyamines, acetylpolyamines could not lower the optimal Mg2+ concentration of protein synthesis, and the degree of stimulation of protein synthesis by acetylpolyamines was small. The addition of N1-acetylspermine did not stimulate cell growth of a polyamine-requiring mutant of Escherichia coli MA261, although acetylspermine was accumulated in the cells. Acetylspermine did not interfere with polyamine stimulation of protein synthesis and cell growth of E. coli MA261. The binding of acetylpolyamines to RNA was very weak, and the binding of polyamines to RNA was not disturbed significantly by the presence of acetylpolyamines. When the growth of E. coli MA261 was stimulated by addition of polyamines, significant amounts of acetylpolyamines were also formed in the cells. These results suggest that acetylation of polyamines, together with polyamine excretion, may regulate the intracellular level of the parent polyamines when excess amounts of polyamines accumulate intracellularly. PMID- 1869517 TI - Expression of cDNA for batroxobin, a thrombin-like snake venom enzyme. AB - The cloned cDNA for batroxobin has been expressed in E. coli. Batroxobin could only be obtained as intracellular aggregates of fusion proteins, fused with a small peptide. To obtain the mature batroxobin, the recognition sequence for thrombin was inserted between the peptide and the mature batroxobin. This fusion protein accumulated in an insoluble form and could easily be purified. After site specific cleavage of the fusion protein with thrombin, recombinant batroxobin was isolated by preparative electrophoresis. Batroxobin with enzymatic activity was obtained by the refolding of recombinant batroxobin. PMID- 1869518 TI - Effects of individual mutations in the P-450(C21) pseudogene on the P-450(C21) activity and their distribution in the patient genomes of congenital steroid 21 hydroxylase deficiency. AB - Recent observations have suggested that the pathological mutations in human P 450(C21) deficiency are generated through gene conversion-like events between the functional gene [P-450(21)B] and the pseudogene [P-450(C21)A]. To address this point more extensively, we investigated the effects of the base changes in the A pseudogene on the P-450(21) activity by using the COS cell expression system. In addition to the defective mutations found previously in the pseudogene, four single base changes with amino acid substitutions of Pro(30), Ile(172), Val(282), or Arg(356) were further identified as causing complete [Arg(356)] or partial [Pro(30), Ile(172), and Val(282)] inactivation of P-450(C21). Blot hybridization analysis of patient DNAs using oligonucleotide probes specific for these mutations revealed that the splicing mutation in the 2nd intron was distributed most frequently in both simple-virilizing and salt-wasting forms. The mutation Ile(172) seemed to be frequent in patients with the less severe simple-virilizing form, whereas the mutation Arg(356), together with other most serious mutations reported previously, was preferentially associated with salt-wasting, the most severe form of the disease. In combination with the present results of the effects of various mutations on the P-50(C21) activity, a survey of the distribution of the various mutations in the patient genomes so far reported suggests that the heterogeneous clinical symptoms of this genetic disease are somehow related to the degree of attenuation of the activities of the mutated gene products. PMID- 1869519 TI - Degradation of L-djenkolate catalyzed by S-alkylcysteine alpha,beta-lyase from Pseudomonas putida. AB - S-Alkylcysteine alpha, beta-lyase [EC 4.4.1.6] of Pseudomonas putida catalyzes alpha,beta-elimination of L-djenkolate [3,3'-methylenedithiobis(2-aminopropionic acid)] to produce pyruvate, ammonia, and S-(mercaptomethyl)cysteine initially. Secondly, S-(mercaptomethyl)-cysteine, which was identified in the form of S (mercaptomethyl)cysteine thiolactone and S-(2-thia-3-carboxypropyl)cysteine in the absence and presence of iodoacetic acid, respectively, is decomposed enzymatically to pyruvate, ammonia, and bis(mercapto)methane, or spontaneously to cysteine, formaldehyde, and hydrogen sulfide. Balance studies showed that 1.3 mol each of pyruvate and ammonia and 0.2 mol each of formaldehyde and cysteine were produced with consumption of 1 mol of L-djenkolate. 1,2,4,5-Tetrathiane, 1,2,4 trithiolane, 1,2,4,6-tetrathiepane, and 1,2,3,5,6-pentathiepane, which are derivatives of bis(mercapto)methane, were also produced during the alpha,beta elimination of L-djenkolate. In addition, a polymer with the general formula of (CH2S)n- was produced as a white precipitate. When the alpha,beta-elimination of L-djenkolate was carried out in the presence of 20 mM iodoacetic acid, neither formaldehyde, cysteine, hydrogen sulfide, or the polymer were formed. Instead, the S-carboxymethyl derivatives of bis(mercapto)methane and S (mercaptomethyl)cysteine were produced in addition to pyruvate and ammonia. PMID- 1869520 TI - The primary structures of two types of the Ulex europeus seed lectin. AB - The complete amino acid sequences of the Ulex europeus anti-H(O) lectins I and II were determined by using a protein sequencer. After digestion with endoproteinases Lys-C and Asp-N of the lectins reduced with 2-mercaptoethanol and modified with iodoacetamide, the resulting peptides were purified by reversed phase high-performance liquid chromatography and subjected to sequence analysis. The complete primary structures of these two Ulex lectins I and II were compared with those of nine lectins already determined, including that of Lotus tetragonolobus anti-H(O) lectin which we have determined. Extensive homologies were found among them. PMID- 1869521 TI - B lymphocyte activation is accompanied by phosphorylation of a 72-kDa protein tyrosine kinase. AB - The cross-linking of membrane IgM on the surface of splenic B lymphocytes or WEHI 231 cells leads to the rapid phosphorylation on tyrosine of a 72-kDa protein as detected in Western blotting experiments using anti-phosphotyrosine antibodies. The 72-kDa phosphoprotein detected in this manner comigrates, in both one- and two-dimensional polyacrylamide gel electrophoresis systems, with PTK72, a 72-kDa protein-tyrosine kinase characterized previously in this laboratory (Zioncheck, T. F., Harrison, M. L., Isaacson, C. C., and Geahlen, R. L. (1988) J. Biol. Chem. 263, 19195-19202). Anti-phosphotyrosine antibodies and anti-PTK72 antibodies immunoprecipitate the same protein-tyrosine kinase from extracts of anti-IgM activated cells as determined by immune complex kinase assays and one-dimensional phosphopeptide mapping. These results indicate that the tyrosine phosphorylation of a 72-kDa protein-tyrosine kinase is an early event in the activation of B lymphocytes via the antigen receptor. PMID- 1869522 TI - Molecular cloning and expression of human Ca(2+)-sensitive cytosolic phospholipase A2. AB - Phospholipases A2 (PLA2s) play a key role in inflammatory processes through production of precursors of eicosanoids and platelet-activating factor. Recently, we described the purification of a novel approximately 100-kDa cytosolic PLA2 (cPLA2) from human monoblast U937 cells that is activated by physiological (intracellular) concentrations of Ca2+ (Kramer, R. M., Roberts, E. F., Manetta, J., and Putnam, J. E. (1991) J. Biol. Chem. 266, 5268-5272). Here we report the isolation of the complementary DNA encoding human cPLA2 and confirm its identity by expression in bacteria and in hamster cells. The predicted 749-amino acid cPLA2 protein has no similarity to the well known secretory PLA2s, but contains a structural element homologous to the C2 region of protein kinase C. The molecular cloning of cPLA2 will allow further studies defining the structure, function, and regulation of this novel PLA2. PMID- 1869524 TI - Biotin derivatives of methotrexate and folate. Synthesis and utilization for affinity purification of two membrane-associated folate transporters from L1210 cells. AB - Biotin derivatives of methotrexate and folate (2-(biotinamido)ethyl-1,3' dithiopropionyldiaminopentyl methotrexate and/or folate), in which carboxyl groups of the functional components are joined by a disulfide-containing spacer, have been synthesized, purified by DEAE-Trisacryl chromatography, and characterized by high pressure liquid chromatography and mass spectrometry. These bifunctional, dissociable probes were utilized for the single-step purification to homogeneity of two folate transport proteins (43 and 39 kDa) from L1210 cells. Treatment of the 39-kDa protein with peptide N-glycosidase F produced a smaller component (32 kDa); the 43-kDa protein, conversely, was unchanged by this procedure. When the 39-kDa transporter in intact cells was labeled with a fluorescein derivative of folate and then treated with phosphoinositol-specific phospholipase C, complete loss of fluorescence was observed. Alternatively, there was no change in fluorescence when the 43-kDa transporter was labeled with a fluorescein derivative of methotrexate and treated with the enzyme. These results indicate that the 43-kDa transporter is a nonglycosylated, integral membrane protein, whereas the 39-kDa counterpart is heavily glycosylated and anchored exofacially to the membrane by a glycosylphosphatidylinositol component. PMID- 1869523 TI - Feedback regulation of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity by dietary cholesterol is not due to altered mRNA levels. AB - Feeding rats diets containing 2% cholesterol markedly reduced hepatic 3-hydroxy-3 methylglutaryl (HMG)-CoA reductase activity but had little effect on mRNA levels. Addition of mevalonolactone to the diet further decreased reductase activity independent of a change in mRNA levels. In contrast, farnesyl pyrophosphate synthetase mRNA levels and enzyme activity were decreased to similar degrees in response to dietary cholesterol. Addition of mevalonolactone to the diet did not further decrease farnesyl pyrophosphate synthetase activity. Dietary cholesterol and mevalonolactone had no effect on mRNA levels for "cellular nucleic acid binding protein" which has been demonstrated to bind the sterol regulatory elements in the HMG-CoA reductase and farnesyl pyrophosphate synthetase promoters. Dietary cholesterol increased cholesterol 7 alpha-hydroxylase mRNA levels as expected. These results suggest that cholesterol-mediated feed-back regulation of hepatic HMG-CoA reductase gene expression does not occur at the level of transcription. PMID- 1869525 TI - Identification of transferrin as a progression factor for ML-1 human myeloblastic leukemia cell differentiation. AB - We have previously demonstrated (Guan X.-P., Hromchak, R. A., and Bloch, A. (1989) Cancer Commun. 1, 111-115) that ML-1 human myeloblastic leukemia cells differentiate to monocyte/macrophage-like cells by the sequential action of competence and progression factors. Tumor necrosis factor-alpha, transforming growth factor-beta, and the phorbol ester tetradecanoylphorbol acetate were found to induce competence, whereas a 77-kDa glycoprotein (DF77) isolated from mitogen stimulated human leukocyte-conditioned medium initiated progression. In this communication we show DF77 to be an isoform of human transferrin. Hemin or soluble iron complexes did not induce differentiation progression, suggesting that the participation of transferrin in ML-1 cell differentiation may not be related to its iron-carrying capacity. PMID- 1869526 TI - Existence of cytosolic phospholipase D. Identification and comparison with membrane-bound enzyme. AB - In a wide variety of cells, phosphatidylcholine hydrolysis in response to diverse agents is catalyzed by phospholipase D (PLD) activities that are believed to be membrane-bound. Indeed, PLD has been detected in membrane fractions of several tissues and cells. We now demonstrate in various bovine tissue including lung, brain, spleen, heart, kidney, thymus, and liver as well as rat lung that a great majority of the detectable PLD activity is cytosolic. This cytosolic PLD activity differs from a less abundant membrane-bound isozyme by chromatographic mobilities on anion exchange and gel filtration columns, by substrate specificity, by substrate concentration dependence, and by divalent cation and detergent effects. Fractionation of the cytosol by anion exchange chromatography enhances PLD activity up to 20-fold, suggesting the presence in the cytosol of PLD inhibitory factor(s). We conclude that mammalian PLD exists in multiple forms and that appropriate selection of assay conditions is critical for observing PLD activity in the cytosol. PMID- 1869527 TI - Function of the N-terminal calcium-binding sites in cardiac/slow troponin C assessed in fast skeletal muscle fibers. AB - Fast skeletal troponin C (sTnC) has two low affinity Ca(2+)-binding sites (sites I and II), whereas in cardiac troponin C (cTnC) site I is inactive. By modifying the Ca2+ binding properties of sites I and II in cTnC it was demonstrated that binding of Ca2+ to an activated site I alone is not sufficient for triggering contraction in slow skeletal muscle fibers (Sweeney, H.L., Brito, R. M.M., Rosevear, P.R., and Putkey, J.A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 9538 9542). However, a similar study using sTnC showed that Ca2+ binding to site I alone could partially activate force production in fast skeletal muscle fibers (Sheng, Z., Strauss, W.L., Francois, J.M., and Potter, J.D. (1990) J. Biol. Chem. 265, 21554-21560). The purpose of the current study was to examine the functional characteristics of modified cTnC derivatives in fast skeletal muscle fibers to assess whether or not either low affinity site can mediate force production when coupled to fast skeletal isoforms of troponin (Tn) I and TnT. Normal cTnC and sTnC were compared with engineered derivatives of cTnC having either both sites I and II active, or only site I active. In contrast to what is seen in slow muscle, binding of Ca2+ to site I alone recovered about 15-20% of the normal calcium activated force and ATPase activity in skinned fast skeletal muscle fibers and myofibrils, respectively. This is most likely due to structural differences between TnI and/or TnT isoforms that allow for partial recognition and translation of the signal represented by binding Ca2+ to site I of TnC when associated with fast skeletal but not slow skeletal muscle. PMID- 1869528 TI - A major substrate of maturation promoting factor identified as elongation factor 1 beta gamma delta in Xenopus laevis. AB - Protein synthesis is believed to be under control of the cell cycle during meiosis and mitosis. Any relationship between substrates for cdc2 kinase and components of the protein synthetic apparatus would therefore be of prime importance. During meiosis of Xenopus laevis oocytes one of the substrates for this kinase is a p47 protein, which is complexed to two other proteins, P36 and P30. Judged from partial amino acid sequence data on P47 and P30, the P30 and P47 proteins were reported to resemble the protein synthetic elongation factors (EF) 1 beta and 1 gamma from Artemia salina (Belle, R., Derancourt, J., Poulhe, R., Capony, J.P., Ozon, R., and Mulner-Lorillon, O. (1989) FEBS Lett. 255, 101-104). This paper shows that the complex composed of P30, P47, and P36 from Xenopus is identical to the complex of EF-1 beta, EF-1 gamma, and EF-1 delta from Artemia according to two criteria. 1) Both stimulate elongation factor 1 alpha-mediated transfer RNA binding to ribosomes and exchange of guanine nucleotides on elongation factor 1 alpha to a comparable degree. 2) Each of the three subunits of the protein complex P30.P47.P36 from Xenopus shows a structural homology with one of the corresponding subunits of EF-1 beta gamma delta from Artemia. Presumably the phosphorylation of EF-1 gamma, which associates with tubulin at least in vitro, is important in processes following the onset of meiosis which is accompanied by a rise of protein synthesis. PMID- 1869529 TI - Platelet-activating factor- and thrombin-induced stimulation of p34cdc2-cyclin histone H1 kinase activity in platelets. AB - Numerous studies of cell cycle control in dividing cells have pointed to the central role of a 34-kDa histone H1 kinase (p34cdc2) complexed with regulatory subunits known as cyclins. We now report that p34cdc2-cyclin may also participate in signal transduction in nonproliferating, terminally differentiated cells, in this instance during sheep platelet activation. Immunological evidence for the presence of a p34cdc2 cognant in sheep platelet cytosol was obtained with antipeptide antibodies raised against peptide sequences in the conserved PSTAIRE and C-terminus regions of murine cdc2. The immunoreactive 32-kDa protein was adsorbed onto p13suc1-Sepharose, which selectively binds p34cdc2. A 58-kDa protein that also bound to p13suc1-Sepharose was identified as cyclin A on the basis of its size and immunoreactivity with two different anticyclin peptide antibodies. The p34cdc2-cyclin A complex was regulated during platelet activation. Its histone H1 phosphorylating activity was stimulated 2-fold in p13suc1-Sepharose extracts from platelets that had been exposed to platelet activating factor or thrombin for 1 min prior to harvesting. Our findings imply that the p34cdc2-cyclin complex may serve alternative functions besides control of cell division. PMID- 1869530 TI - Ca(2+)-insensitive modulation of a K+ conductance by inositol polyphosphates. AB - Macrophages derived from phorbol ester-induced human leukemic (HL-60) cells exhibit a voltage-activated inward rectifying potassium conductance which was modulated by macrophage colony-stimulating factor (Wieland, S. J., Chou, R. H., and Gong, Q. H. (1990) J. Cell. Physiol. 142, 643-651). Roles of intracellular messengers in this regulatory mechanism were investigated. Intracellular dialysis with inositol 1,3,4,5-tetrakisphosphate (IP4) or inositol 1,4,5-trisphosphate during tight-seal whole cell recording produced a rapid increase in the inward rectifying conductance. Changes in intracellular Ca2+ levels alone did not reproduce the stimulatory effect of these modulators. Intracellular dialysis with guanosine 5'-O-(thiotriphosphate) (GTP gamma S) resulted in profound inhibition of this conductance. These data suggest a novel cellular function for inositol polyphosphates, particularly IP4, and show antagonistic modulation with GTP gamma S on a human macrophage inward rectifier. PMID- 1869531 TI - Cysteinyl peptides of pig heart NADP-dependent isocitrate dehydrogenase that are modified upon inactivation by N-ethylmaleimide. AB - Pig heart NADP-specific isocitrate dehydrogenase is inactivated by N ethylmaleimide (NEM) (Colman, R. F., and Chu, R. (1970) J. Biol. Chem. 245, 601 607), and is completely protected against inactivation, but not against the incorporation of NEM, by isocitrate plus Mn2+. We have now treated the enzyme with [3H]NEM in the absence and presence of isocitrate plus Mn2+, digested it with trypsin, and isolated and sequenced the labeled Cys peptides. In the inactive enzyme, two major peptides, SSGGFVWACK and DLAGCIHGLSNVK, and two minor peptides, CATITPDEAR and EPIICK, were labeled at Cys. Upon reaction with [3H]NEM in the presence of isocitrate plus Mn2+, full catalytic activity was retained and only DLAGCIHGLSNVK was labeled; the Cys of this peptide is therefore not essential for catalysis. The modification of SSGGFVWACK appears to be the major cause of inactivation by NEM. The Cys in SSGGFVWACK may have a catalytic role, most likely in the strengthened binding of Mn2+ in the presence of isocitrate. Isocitrate dehydrogenase was carboxymethylated under denaturing conditions with [14C]iodoacetate and digested with trypsin; 6 unique labeled Cys peptides, containing 6 unique Cys residues, were purified and sequenced. Six corresponding peptides were isolated from enzyme treated under denaturing conditions with [3H]NEM. These results eliminate the previous uncertainty regarding the number of Cys residues in the enzyme. A comparison of the sequences of the NH2-terminal 30 residues and the 6 Cys peptides of the pig heart NADP-dependent isocitrate dehydrogenase with the Escherichia coli NADP enzyme provides evidence for great dissimilarity between the two enzymes. PMID- 1869532 TI - Ribosomes pause at specific sites during synthesis of membrane-bound chloroplast reaction center protein D1. AB - Photosynthetic reaction center protein D1 contains five membrane-spanning alpha helices which form binding sites for pheophytin, chlorophyll, carotenoids, quinone, Fe2+, and probably Mn2+. D1 translation intermediates of 15 to 28 kD were detected when isolated chloroplasts were pulse-labeled with [35S]methionine. The D1 translation intermediates were associated with membrane polysomes and can be chased into full length D1. The sites of translation pausing were determined by mapping the distribution of ribosomes on D1 mRNA using toeprint analysis. Clusters of toeprint signals were generated by D1 mRNA associated with membranes but not by D1 mRNA in nonpolysomal fractions of the soluble phase or phenol extracted mRNA. The distribution of ribosomes on D1 mRNA determined by toeprint analysis was consistent with D1 translation intermediates observed with pulse labeling. Ribosome pausing may facilitate co-translational binding of co-factors such as chlorophyll to D1 and aid the integration of D1 into thylakoid membranes. PMID- 1869533 TI - Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family. AB - The beta-adrenergic receptor kinase (beta ARK) specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors. Structural features of this enzyme have been elucidated recently by the isolation of a cDNA that encodes bovine beta ARK. Utilizing a catalytic domain fragment of the beta ARK cDNA to screen a bovine brain cDNA library we have isolated a clone encoding a beta ARK-related enzyme which we have termed beta ARK2. Overall, this enzyme has 85% amino acid identity with beta ARK, with the protein kinase catalytic domain having 95% identity. The ability of beta ARK2 to phosphorylate various substrates was studied after expression in COS 7 cells. Although beta ARK2 is essentially equiactive with beta ARK in phosphorylating an acid-rich synthetic model peptide it was only approximately 50% as active when the substrate was the agonist-occupied beta 2-adrenergic receptor and only approximately 20% as active toward light-bleached rhodopsin. As with beta ARK, phosphorylation of the receptor substrates by beta ARK2 was completely stimulus dependent. RNA blot analysis with selected bovine tissues reveals an mRNA of 8 kilobases with a distribution similar to that of beta ARK. More detailed RNA analysis using a ribonuclease protection assay in various rat tissues suggests that the beta ARK2 message is present at much lower levels (typically 10-20%) than the beta ARK message. In the rat the beta ARK2 mRNA is localized predominantly in neuronal tissues although low levels are also observed in various peripheral tissues. The beta ARK2 gene has been localized to a region of mouse chromosome 5 whereas the beta ARK gene is localized on mouse chromosome 19. These data suggest the existence of a "family" of receptor kinases which may serve broadly to regulate receptor function. PMID- 1869534 TI - Erythropoietin induces Raf-1 activation and Raf-1 is required for erythropoietin mediated proliferation. AB - Erythropoietin mediates the rapid phosphorylation of Raf-1 in the murine cell lines HCD-57 and FDC-P1/ER, which proliferate in response to this cytokine. Phosphorylation occurs at both serine and tyrosine residues and as such is similar to the Raf-1 phosphorylation seen after interleukin-3 (IL-3), granulocyte macrophage colony-stimulating factor, and interleukin-2 stimulation in other murine cell lines. Such data suggest that these growth factors may share a common mechanism(s) of Raf-1 phosphorylation. Furthermore, in association with Raf-1 phosphorylation, erythropoietin induces a 2-3-fold increase in Raf-1 kinase activity as measured in immune complex kinase assays in vitro. Finally, a c-raf antisense oligodeoxyribonucleotide, which specifically decreases intracellular Raf-1 levels, also substantially inhibits both erythropoietin and IL-3-directed DNA synthesis. Together, these results provide evidence that activated Raf-1 is a necessary component of erythropoietin and IL-3 growth signaling pathways. PMID- 1869535 TI - Ca(2+)-dependent structural transitions of the platelet glycoprotein IIb-IIIa complex. Preparation of stable glycoprotein IIb and IIIa monomers. AB - The platelet membrane glycoprotein (GP) IIb-IIIa complex is the receptor for adhesive proteins on activated platelets that mediates platelet aggregation. In the present study, factors affecting the structural stability of the purified GP IIb-IIIa complex and the dissociated subunits were investigated. Purified GP IIb IIIa was incubated in various Ca2+ concentrations, and the percentage of dissociated subunits was quantitated by sucrose gradient sedimentation. Two Ca(2+)-dependent transitions were observed, one at about 60 microM Ca2+, where half of the complexes became dissociated, and the other at 0.1 microM Ca2+, where half of the dissociated subunits became incapable of reforming heterodimer complexes when higher Ca2+ concentrations were readded. This loss in ability to reform heterodimer complexes was caused primarily by a Ca(2+)-dependent transition in GP IIIa, leading to an apparent unfolding of this subunit, followed by the formation of high molecular weight aggregates. The formation of these aggregates was time- and temperature-dependent and could not be reversed by added Ca2+. Although Mg2+ prevented dissociation of GP IIb-IIIa, it failed to promote reassociation of the dissociated subunits. Based on these findings, conditions were developed for the preparation of dissociated GP IIb and GP IIIa such that 70% of the subunits remained functional in that they retained the ability to reform heterodimer complexes. PMID- 1869536 TI - Biosynthesis of the trichothecene 3-acetyldeoxynivalenol. Identification of the oxygenation steps after isotrichodermin. AB - Upon feeding an excess of the substrate isotrichodermin, five tricyclic metabolites accumulated in Fusarium culmorum cultures. These compounds were also identified as transient intermediates of trichothecene biosynthesis by kinetic pulse labeling. Their structures were characterized by spectroscopic techniques (1H NMR, 13C NMR, 2H NMR, and nuclear Overhauser effect difference experiments) as: 1, 15-deacylcalonectrin; 2, calonectrin; 3, 7-hydroxyisotrichodermin; 4, 8 hydroxyisotrichodermin; and 5, 7, hydroxycalonectrin. Four of these metabolites (1-4) were rigorously proven to be biosynthetic precursors to 3 acetyldeoxynivalenol. Indeed, their deuteriated derivatives were shown to be incorporated very efficiently into 3-acetyldeoxynivalenol by 2H-NMR. In addition, our experimental data suggests that the first oxygenation step after isotrichodermin is at C-15, producing 15-deacylcalonectrin. PMID- 1869537 TI - NMR study of the active site of resting state and cyanide-inhibited lignin peroxidase from Phanerochaete chrysosporium. Comparison with horseradish peroxidase. AB - One- and two-dimensional 1H NMR spectroscopy has been used to probe the active site of the high spin ferric resting state and the low spin, cyanide-inhibited derivative of isozyme H2 of the lignin peroxidase, LiP, from Phanerochaete chrysosporium strain BKM 1767. One-dimensional NMR revealed a resting state LiP that is five coordinate at 25 degrees C with an electronic structure similar to that of horseradish peroxidase, HRP. Differential paramagnetic relaxivity was used to identify the C beta H signals of the axial His177. A combination of bond correlation spectroscopy and nuclear Overhauser effect spectroscopy of cyanide inhibited LiP (LiP-CN) has allowed the assignment of all resolved heme resonances without recourse to isotope labeling, as well as those of the proximal His177 and the distal His48. The surprising effectiveness of the two dimensional NMR methods on such a large and paramagnetic protein indicates that such two dimensional experiments can be expected to have major impact on solution structure determination of diverse classes of heme peroxidases. The two dimensional NMR data of LiP-CN reveal a heme contact shift pattern that reflects a close similarity to that of HRP-CN, including the unusual in-plane trans and cis orientation of the 2- and 4-vinyls. The axial His177 also exhibits the same orientation relative to the heme as in HRP-CN. The proximal His177 contact shifted resonances of both the low spin LiP-CN and high spin LiP are shown to reflect significantly reduced hydrogen bond donation by, or imidazolate character for, the axial histidine in LiP relative to HRP, which may explain the higher redox potential of LiP. The signals are identified for a distal residue that originates from the protonated His48 with disposition relative to the heme similar to that found for the distal His42 in HRP-CN. In contrast, the absence of any resolved signals attributable to an Arg44 in LiP-CN suggest that this distal residue has an altered orientation relative to the heme compared with that of the conserved Arg38 in HRP-CN (Thanabal, V., de Ropp, J. S., and La Mar, G. N. (1987) J. Am. Chem. Soc. 109, 7516-7525). PMID- 1869538 TI - Only multimers of a synthetic peptide of human apolipoprotein E are biologically active. AB - Plasma apolipoprotein E (apoE) is a ligand for the cellular uptake of cholesterol rich plasma lipoproteins. ApoE also inhibits mitogen-stimulated lymphocyte proliferation and gonadotropin-stimulated ovarian theca/interstitial cell androgen production. To address the mechanism(s) by which apoE is active and to understand its interaction with the target cells, we prepared and examined the inhibitory activity of a series of apoE synthetic peptides. ApoE peptides representing amino acid residues 93-112, 141-155, 161-171, 172-182, and 174-193 were not active in either bioassay. However, specific inhibition of both lymphocyte proliferation and ovarian androgen production was observed with a self conjugate of peptide-(141-155). Furthermore, a synthesized dimeric peptide representing two repeats of sequence-(141-155) (i.e. (141-155)-(141-155] was active as well. In both bioassays, the inhibition observed was not a result of direct cell killing. Furthermore, these apoE peptides exhibited activities with characteristics that were shared with those of native apoE. The results indicate that amino acid residues 141-155 of apoE are responsible for the biological activity of apoE. Furthermore, the results suggest that dimers or multimers of native apoE may be a biologically important species. PMID- 1869539 TI - Effects of a leucine analog on growth hormone processing and secretion by cultured cells. AB - Bovine and rat growth hormones (bGH and rGH, respectively) possess signal peptides that direct the hormone to the secretory pathway and are proteolytically cleaved prior to secretion. Previous in vitro translation studies indicated that incorporation of the polar leucine analog beta-hydroxyleucine into de novo synthesized polypeptides inhibits signal peptide function. To test the effects of this analog on GH secretion by cultured animal cells, transfections of mouse L cells with a bGH expression plasmid or metabolic labeling of endogenous rGH in anterior pituitary cells was performed in the absence or presence of beta hydroxyleucine. Transient expression of bGH in mouse L-cells or endogenous expression of rGH in anterior pituitary cells resulted in an accumulation of GH in the culture medium. Treatment with beta-hydroxyleucine resulted in a block in secretion as evidenced by an accumulation of GHs within these cells. Amino terminal sequencing of the intracellular form of the analog-substituted GHs demonstrated accurate signal peptide cleavage. In contrast, in vitro translations of bGH RNA performed in the presence of beta-hydroxyleucine and microsomal membranes resulted in the inhibition of signal peptide cleavage. The results suggest that beta-hydroxyleucine can uncouple signal peptide processing and protein secretion in cultured cells. PMID- 1869540 TI - Squid low molecular weight neurofilament proteins are a novel class of neurofilament protein. A nuclear lamin-like core and multiple distinct proteins formed by alternative RNA processing. AB - The primary structure of the major 60-kDa squid low molecular mass neurofilament protein (NF60) and a related 70-kDa neurofilament protein have been determined from cDNA clones isolated from a squid brain cDNA library. Structural analysis suggests that the squid NF60 and NF70 neurofilament genes and proteins are remarkably distinct from vertebrate neuronal intermediate filaments characterized previously. Both proteins are encoded on mRNAs generated by alternative RNA processing of the primary transcript of a single gene. Among the known intermediate filament proteins, NF60 and NF70 neurofilament proteins show highest similarity to an epithelial intermediate filament protein from Helix pomatia, a gastropod mollusk, and are less similar to vertebrate neurofilaments. The length of the alpha-helical rod domain in the NF60 and NF70 proteins was reminiscent of the vertebrate nuclear lamins, 6 heptads longer than is found in all known vertebrate cytoplasmic intermediate filaments, in particular the vertebrate neurofilaments. These distinct structural properties suggest that the vertebrate and invertebrate low molecular weight neurofilaments evolved independently from primordial intermediate filament proteins. PMID- 1869541 TI - Phosphatidylinositol-linked glycans and phosphatidylinositol-anchored proteins of Tetrahymena mimbres. AB - The insoluble residue from Tetrahymena mimbres cells that had been preincubated in vivo for 2 h with [3H]myristic acid and then exhaustively delipidated with organic solvents retained radioactivity, principally in material which migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular mass of 10-14 kDa. This material was extractable from the delipidated cell residue with organic solvents known to solubilize phosphatidylinositol glycans (PI glycans). The same material could also be labeled with [3H]inositol, [14C]glucosamine, and [3H] ethanolamine. When the delipidated residue of cells labeled for 2 h with [3H]myristate was treated with phosphatidylinositol-specific phospholipase C or nitrous acid, much of the associated radioactivity was released. A similar release was obtained using the putative PI glycan fraction extracted from the cell residue. After further purification by thin layer chromatography, this latter material was hydrolyzed with HCl and shown to contain fatty acids, alkylglyceryl ethers, phosphate, inositol, glucosamine, mannose, and ethanolamine. The findings indicate that T. mimbres contains PI glycans resembling in structure those recently characterized in trypanosomes and mammalian cells. As the time of incubation with the radiotracers enumerated above was increased to 6-24 h, increasing amounts of radioactivity appeared in the 22 27-kDa region of sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels. This higher molecular weight material is shown in the companion paper (Pak, Y., Ryals, P.E., and Thompson, G.A., Jr. (1991) J. Biol. Chem. 266, 15054-15059) to be released by in vivo phosphatidylinositol-specific phospholipase C treatment. Thus T. mimbres contains a pool of free PI glycans and at least one phosphatidylinositol-anchored protein. PMID- 1869542 TI - The minimal essential sequence for a major cell type-specific adhesion site (CS1) within the alternatively spliced type III connecting segment domain of fibronectin is leucine-aspartic acid-valine. AB - Fibronectin contains at least two major domains that support cell adhesion. One is the central cell-binding domain that is recognized by a variety of cell types via the integrin alpha 5 beta 1. The second, originally identified by its ability to support melanoma cell adhesion, is located in the alternatively spliced type III connecting segment (IIICS). A dominant cell type-specific adhesion site within the IIICS has been localized to a peptide designated as CS1 comprising its amino-terminal 25 residues. The receptor for CS1 is the integrin alpha 4 beta 1. We have synthesized a variety of peptides with overlapping sequences in order to identify the minimum active amino acid sequence of this major cell adhesion site. A peptide comprising the carboxyl-terminal 8 amino acids of CS1, EILDVPST, was found to support melanoma cell spreading, while all peptides without this sequence had little or no activity. Two smaller overlapping pentapeptides, EILDV and LDVPS, were also active, whereas EILEV, containing a conservative substitution of Glu for Asp, was inactive. These data suggested that the minimum sequence for cell adhesion activity is Leu-Asp-Val, the tripeptide sequence common to both active peptides. This prediction was confirmed by the observed ability of the Leu-Asp-Val peptide itself to block spreading on fibronectin, whereas Leu-Glu-Val was inactive. Interspecies amino acid sequence comparison also supports the importance of the LDV sequence, since it is completely conserved in the IIICS regions of human, rat, bovine, and avian fibronectins. PMID- 1869543 TI - Characterization of cDNA clones encoding a novel calcium-activated neutral proteinase from Schistosoma mansoni. AB - To identify and characterize Schistosoma mansoni proteins that are recognized by infected hosts, we have used a pool of sera from infected humans to screen cDNA libraries constructed from poly(A)+ mRNA of adult S. mansoni. The deduced amino acid sequences of the three isolated clones showed a high degree of similarity to the large subunit of calcium-activated neutral proteinase (CANP) from humans and chicken. These overlapping clones, which include a nearly full-length clone with an open reading frame of 758 amino acid residues, together encode the entire large subunit of CANP. The deduced sequence of this S. mansoni protein can be divided into four domains (I-IV) that include the two domains characteristic of other large subunits of CANP: a thiol-protease domain (II) and a calcium-binding domain (IV) containing EF hand motifs. However, the schistosome protein is unique in having only three EF hand motifs in the calcium-binding domain and in having an additional EF hand motif that is shared between domains II and III. We have shown that these EF hand motifs are capable of binding 45Ca2+. Furthermore, the large subunit is S. mansoni contains an NH2-terminal sequence of 28 residues that is absent from the mammalian CANPs and has a high degree of similarity to the presumed receptor binding sequence of colicin Ia and Ib. PMID- 1869544 TI - Perhydroxyl radical (HOO.) initiated lipid peroxidation. The role of fatty acid hydroperoxides. AB - It is demonstrated that the perhydroxyl radical (HOO., the conjugate acid of superoxide (O2-], initiates fatty acid peroxidation (a model for biological lipid peroxidation) by two parallel pathways: fatty acid hydroperoxide (LOOH) independent and LOOH-dependent. Previous workers (Gebicki, J. M., and Bielski, B. H. J. (1981) J. Am. Chem. Soc. 103, 7020-7025) demonstrated that HOO., generated by pulse radiolysis, initiates peroxidation in ethanol/water fatty acid dispersions by abstraction of the bis-allylic hydrogen atom from a polyunsaturated fatty acid. Addition of O2 to the fatty acid radicals forms peroxyl radicals (LOO.s), the chain-propagating species of lipid peroxidation. In this work it is demonstrated that HOO., generated either chemically (KO2) or enzymatically (xanthine oxidase), is a good initiator of fatty acid peroxidation in linoleic acid ethanol/water dispersions; O2- serves only as the source of HOO., and HOO. initiation can be observed at physiologically relevant pH values. In contrast to the previous results, the initiating effectiveness of HOO. is related directly to the initial concentrations of LOOHs in the lipids to be peroxidized. This defines a LOOH-dependent mechanism for fatty acid peroxidation initiation by HOO., which parallels the previously established LOOH-independent pathway. Since the LOOH-dependent pathway is much more facile than the LOOH independent pathway, LOOH is the kinetically preferred site of HOO. attack in these systems. Experiments comparing HOO./LOOH-dependent fatty acid peroxidation with transition metal- and peroxyl radical-initiated peroxidation rule out the participation of the latter two species as initiators, which defines the HOO./LOOH initiation system as mechanistically unique. LOOH product studies are consistent with either a direct or indirect hydrogen atom transfer between LOOH and HOO. to yield LOO.s, which propagate peroxidation. The LOOH-dependent pathway of HOO.-initiated fatty acid peroxidation may be relevant to mechanisms of lipid peroxidation initiation in vivo. PMID- 1869545 TI - Kinetics and compartmentation of energy metabolism in intact skeletal muscle determined from 18O labeling of metabolite phosphoryls. AB - Analyses of isolated intact diaphragm muscle show that at rest only about 30% of the total cellular Pi is metabolically reactive as indicated by 18O incorporation from [18O]water, whereas up to 90% becomes metabolically active incrementally with contractile frequency. Kinetics of [gamma-18O]ATP appearance show that about 90% of the cellular ATP is metabolically active and suggest slowly and rapidly metabolizing compartments of ATP in resting muscle and only rapidly metabolizing compartments in contracting muscle. Rates of [18O]creatine phosphate [( 18O]CrP) appearance are consistent with creatine kinase-catalyzed phosphoryl exchange functioning in an obligatory phosphoryl shuttle system. In noncontracting muscle, ATP turnover rate was 83 nmol.mg protein-1.min-1, and the P/O ratio was determined to be 3.2. ATP utilization increases in direct proportion to contractile frequency with each contracture consuming the equivalent of 0.96 nmol of ATP.mg protein-1 or 2.5-3.5 molecules of ATP/myosin active site. Basal concentrations of nucleotide polyphosphates are not altered when ATP utilization rates increase during contraction. At high contractile frequencies, decreases in CrP concentration occur, but this accounts for less than 4% of total high energy phosphoryls consumed. If metabolic intermediates are free in the aqueous cellular cytosol, each twitch contracture would result in a decrease in ATP concentration of no more than 2% and increases in ADP and AMP concentrations of less than 20 and 7%, respectively. Thus, changes in metabolite concentration must be highly localized or metabolic regulation can be accomplished by a nonallosteric mechanism. PMID- 1869546 TI - Effects of transformation with the v-src oncogene on inositol phosphate metabolism in rat-1 fibroblasts. D-myo-inositol 1,4,5,6-tetrakisphosphate is increased in v-src-transformed rat-1 fibroblasts and can be synthesized from D myo-inositol 1,3,4-trisphosphate in cytosolic extracts. AB - Rat-1 fibroblasts transformed with the v-src oncogene show a 6-fold increase in the apparent amount of an inositol polyphosphate which has a high performance liquid chromatography (HPLC) elution characteristic of the D/L-myo-inositol 1,4,5,6-tetrakisphosphate enantiomeric pair (Johnson, R.M., Wasilenko, W.J., Mattingly, R.R., Weber, M.J., and Garrison, J.C. (1989) Science 246, 121-124). By chemical and enzymatic analysis, the structure of this compound produced in both normal and v-src-transformed rat-1 fibroblasts has been determined to be principally D-myoinositol 1,4,5,6-tetrakisphosphate (D-Ins(1,4,5,6)P4). Chronic stimulation with endothelin-1 in the presence of Li+ significantly increased the amount of D/L-Ins(1,4,5,6)P4 only in the v-src-transformed rat-1 cells, suggesting that production of this compound may be remotely coupled to long term agonist-induced phosphatidylinositol turnover. Further evidence for such a link is provided by the progressive loss of D-Ins(1,4,5,6)P4 from the normal cells deprived of serum stimulation. To define a possible synthetic pathway for D Ins(1,4,5,6)P4, cytosolic extracts of normal and v-src-transformed cells were incubated with [3H]inositol polyphosphates, and the reaction products were identified by HPLC elution and chemical analysis. Although inositol 1,3,4 trisphosphate 6-kinase activity was prominent in extracts of both normal and transformed cells, only the cytosol from v-src-transformed cells ultimately formed measurable amounts of D-Ins(1,4,5,6)P4 from [3H]inositol 1,3,4 trisphosphate. Approximately 6% of 0.1 microM inositol 1,3,4-trisphosphate was converted to D-Ins(1,4,5,6)P4 during a 2-h incubation at 37 degrees C. Inositol pentakisphosphate was identified as a likely intermediate in this conversion, and extracts of both normal and transformed cells converted [3H]inositol 1,3,4,5,6 pentakisphosphate to D-Ins(1,4,5,6)P4. The synthetic pathway described is consistent with the long term regulation of D/L-Ins(1,4,5,6)P4 levels in rat-1 fibroblasts seen in response to src transformation, serum withdrawal, and chronic endothelin treatment, and identifies several new potential interactions between the pathways of inositol polyphosphate metabolism and those of src transformation. PMID- 1869547 TI - Stacking energies in DNA. AB - Variations in base mono- and dipoles result in variations in stacking energies for the 10 unique neighbor pairs in DNA. Stacking energies for pair M on N, expressed as TMN, were derived by matrix decomposition of a large set of linear algebraic expressions relating the measured Tm for subtransitions emanating from large polymeric DNAs, and the fractional neighbor frequencies, fMN, for the domains responsible for the transitions, Tm = sigma fMNTMN. Tm were determined for subtransitions that dissociate in approximately all-or-none fashion in high resolution melting profiles of partially deleted and recombinant forms of pBR322 DNA. Three different analytical maneuvers were undertaken to resolve subtransitions: site-specific cleavage of domains; deletion of domains; and addition of domains. Three dozen domains of widely divergent, quasi-random neighbor frequencies were identified and assigned, resulting in a unique set of values for TMN with standard deviation, sigma = +/- 0.23 degree C. The average difference between calculated and experimental Tm for domains is only +/- 0.17 degree C, indicating that the thermodynamic properties of these domains are not in any way unusual. Assuming delta S to be constant for all pairs, the corresponding delta HMN are found to have a precision of +/- 10 calories.mol-1 and an accuracy of +/- 606 calories.mol-1. TMN used to calculate melting curves by statistical mechanical analysis of sequences of the different plasmid specimens in this study were in quantitative agreement with observed curves for most sequences. These TMN differ significantly from those determined previously and also correlate poorly with values determined by quantum chemical analysis. Stabilities of neighbor pairs, expressed as the difference in free energy between that for a given pair (MN) and that for the average of like pairs (M, N), depend on the relationship of stacked purines and pyrimidines as follows. delta delta Gpu-py(-466 cal) greater than delta delta Gpu-pu(+52 cal) greater than delta delta Gpy-pu(+335 cal) Differences between experimental Tm and Tm calculated with TMN for the isolated neighbor pairs in the B-conformation are useful in the identification of altered structures and unusual modes of dissociation of helixes. A significantly higher Tm is observed for the highly biased repeated sequence synthetic helixes dA.dT, d(AGC).d(GCT), and d(GAT).d(ATC), reflecting auxiliary sources of stability such as bifurcated hydrogen bonds and/or altered structures for these helixes. PMID- 1869548 TI - Parinaric acids as probes of binding domains in neutrophil elastase. AB - Human neutrophil elastase has an extended hydrophobic substrate binding site which serves as a target for a number of hydrophobic inhibitors. We show here that the parinaric acids, fluorescent-conjugated tetraenoic fatty acids of plant origin, are inhibitors of neutrophil elastase. cis-Parinaric acid (cis-PA) interacts with the enzyme in two inhibitory modes. The high affinity interaction (Ki = 55 +/- 6 nM) results in partial noncompetitive inhibition of amidolytic activity, with 82% residual activity. A lower affinity interaction with cis-PA (Ki = 4 +/- 1 microM) results in competitive inhibition. trans-PA also acts as a high affinity partial noncompetitive inhibitor of elastase with a Ki equal to that for cis-PA but has no low affinity competitive inhibitory action. The endogenous fluorescence from the 3 tryptophan residues in elastase is partially quenched on binding cis- or trans-PA. Dependence of quenching of tryptophan fluorescence on PA concentration is consistent with binding to a single site with an apparent Kd of 26 +/- 3 nM, which may be equivalent to the high affinity partial noncompetitive inhibitory binding mode. Analysis of quenching according to the modified Forster theory of energy transfer developed by Snyder and Freire (Snyder, B., and Freire, E. (1982) Biophys. J. 40, 137-148) leads to an estimate of apparent closest indole-PA distance of 13 +/- 3 A. Fluorescence of either cis- or trans-PA is apparently unperturbed upon binding in the high affinity mode to elastase, but at micromolar cis-PA concentrations, binding to elastase results in a blue shift and 20% increase in intensity of PA emission, suggesting that the lower affinity competitive inhibitory binding mode of binding to elastase provides a hydrophobic environment for cis-PA. PMID- 1869549 TI - Expression of rat serum amyloid A1 gene involves both C/EBP-like and NF kappa B like transcription factors. AB - Serum amyloid A (SAA) is a major acute-phase protein synthesized and secreted mainly by the liver. During inflammation, its expression is increased by 1000 fold as the result of greatly increased gene transcription. In this study, we analyzed the cis-acting regulatory elements and trans-acting factors important for the expression of the rat SAA1 gene. A DNA fragment containing 304 base pairs (bp) of 5'-flanking sequences of the SAA1 gene was fused to a reporter gene, chloramphenicol acetyltransferase (CAT), and the resulting construct, pSAA1/CAT ( 304), was used to assess the function of the 5'-flanking sequences by transient transfection assay. pSAA1/CAT (-304) was not expressed or expressed at very low levels in both the liver- and nonliver-derived cells. However, when stimulated with conditioned medium prepared from mixed lymphocyte cultures, recombinant interleukin 1, or 12-O-tetradecanoylphorbol-13-acetate, expression of the pSAA1/CAT (-304) hybrid gene was induced 15-20-fold, but only in liver-derived cells. Further functional analysis demonstrated that a 66-bp DNA fragment conferred cytokine responsiveness onto a heterologous thymidine kinase promoter both in liver and nonliver cells. Footprint analysis with the Hep3B nuclear proteins revealed four protected regions in the 5'-flanking region of the SAA1 gene. The pattern of protection was identical with nuclear extracts prepared from either unstimulated or conditioned medium-treated Hep3B cells. Two of these footprint regions were identified as binding sites for C/EBP or C/EBP-related proteins, with the distal region having about 10-fold higher binding affinity than the proximal region. One additional cis-element formed a specific protein DNA complex only with the nuclear proteins from TPA- or conditioned medium treated Hep3B cells. This cis-element shares sequence identity with nuclear factor NF kappa B binding sites. The finding of a NF kappa B binding site within the 66-bp cytokine-responsive fragment further suggests its functional importance in the regulation of SAA1 gene expression. Our results suggest that C/EBP- and NF kappa B-related proteins may be important regulatory factors that contribute both to tissue specificity and to the high rate of SAA transcription in response to inflammatory mediators. PMID- 1869550 TI - Structural requirements for transformation of substrates by the (S)-adenosyl-L methionine:delta 24(25)-sterol methyl transferase. AB - The membrane-bound enzyme of microsomes obtained from sunflower embryos that catalyzes the bi-substrate transfer reaction whereby the methyl group of (S) adenosyl-L-methionine is transferred to C-24 of the sterol side chain has been investigated. Optimal incubation conditions for assay of the microsomal (S) adenosyl-L-methionine:sterol delta 24-methyl transferase (SMT) have been established for the first time. The microsomal preparation was found to catalyze the formation of a delta 24(28)-sterol and to be free of contaminating methyl transferase enzymes, e.g. those which form delta 23-24 methyl sterols (cyclosadol) and delta 25-24 beta-methyl sterols (cyclolaudenol) and other sterolic enzymes which might transform the acceptor molecule to metabolites which could compete in the assay with the test substrate. From a series of incubations with 27 sterol and sterol-like (triterpenoids) substrates of which 23 compounds possessed a 24,25-double bond, we observed a marked dependence on precise structural features and three-dimensional shape of the acceptor molecule in its ability to be transformed by the SMT. In contrast to the yeast SMT where cycloartenol fails to bind to the SMT and zymosterol is the best substrate for methylation, the sunflower SMT studied here utilizes cycloartenol preferentially to zymosterol and the other substrates. Of the chemical groups which distinguishes cycloartenol, a free 3 beta-OH,9 beta,19-cyclopropyl group, trimethylated saturated nucleus, and delta 24-double bond, only the nucleophilic centers at C-3 and C-24 were obligatory for substrate binding and methylation. Of the bent or flat conformations which cycloartenol may orient in the enzyme substrate complex, our results indicate a selection for acceptor molecules which possess the shape that closely resembles the crystal state and solution orientation of cycloartenol which is now known to be flat rather than bent (Nes, W. D., Benson, M., Lundin, R. E., and Le, P. H. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 5759-5763). PMID- 1869551 TI - Calcium influx in a rat mast cell (RBL-2H3) line. Use of multivalent metal ions to define its characteristics and role in exocytosis. AB - An increase in concentration of cytosolic Ca2+ ([Ca2+]i) is associated with an accelerated influx of 45Ca2+ when cultured RBL-2H3 cells are stimulated with either antigen or analogs of adenosine although these agents act via different receptors and coupling proteins (Ali, H., Cunha-Melo, J.R., Saul, W.F., and Beaven, M.A. (1990) J. Biol. Chem. 265, 745-753). The same mechanism probably operates for basal Ca2+ influx in unstimulated cells and for the accelerated influx in stimulated cells. This influx had the following characteristics. 1) It was decreased when cells were depolarized with high external K+; 2) it was blocked by other cations (La3+ greater than Zn2+ greater than Cd2+ greater than Mn2 = Co2+ greater than Ba2+ greater than Ni2+ greater than Sr2+) either by competing with Ca2+ at external sites (e.g. La3+ or Zn2+) or by co-passage into the cell (e.g. Mn2+ or Sr2+); and 3) the inhibition of influx by K+ and the metal ions had exactly the same characteristics whether cells were stimulated or unstimulated even though influx rates were different. The dependence of various cellular responses on influx of Ca2+ was demonstrated as follows. The stimulated influx of Ca2+, rise in [Ca2+]i, and secretion, could be blocked in a concentration-dependent manner by increasing the concentration of La3+, but concentrations of La3+ (greater than 20 microM) that suppressed influx to below basal rates of influx markedly suppressed the hydrolysis of inositol phospholipids (levels of inositol 1,4,5-trisphosphate were unaffected). Some metal ions, e.g. Mn2+ and Sr2+, however, supported the stimulated hydrolysis of inositol phospholipid and some secretion in the absence of Ca2+. Thus a basal rate of influx of Ca2+ was required for the full activation of inositol phospholipid hydrolysis, but in addition an accelerated influx was necessary for exocytosis. PMID- 1869552 TI - Identification of sequence segments forming the alpha-bungarotoxin binding sites on two nicotinic acetylcholine receptor alpha subunits from the avian brain. AB - The relationship between neuronal alpha-bungarotoxin binding proteins (alpha BGTBPs) and nicotinic acetylcholine receptor function in the brain of higher vertebrates has remained controversial for over a decade. Recently, the cDNAs for two homologous putative ligand binding subunits, designated alpha BGTBP alpha 1 and alpha BGTBP alpha 2, have been isolated on the basis of their homology to the N terminus of an alpha BGTBP purified from chick brain. In the present study, a panel of overlapping synthetic peptides corresponding to the complete chick brain alpha BGTBP alpha 1 subunit and residues 166-215 of the alpha BGTBP alpha 2 subunits were tested for their ability to bind 125I-alpha BGT. The sequence segments corresponding to alpha BGTBP alpha 1-(181-200) and alpha BGTBP alpha 2 (181-200) were found to consistently and specifically bind 125I-alpha BGT. The ability of these peptides to bind alpha BGT was significantly decreased by reduction and alkylation of the Cys residues at positions 190/191, whereas oxidation had little effect on alpha BGT binding activity. The relative affinities for alpha BGT of the peptide sequences alpha BGTBP alpha 1-(181-200) and alpha BGTBP alpha 2-(181-200) were compared with those of peptides corresponding to the sequence segments Torpedo alpha 1-(181-200) and chick muscle alpha 1-(179-198). In competition assays, the IC50 for alpha BGTBP alpha 1-(181 200) was 20-fold higher than that obtained for the other peptides (approximately 2 versus 40 microM). These results indicate that alpha BGTBP alpha 1 and alpha BGTBP alpha 2 are ligand binding subunits able to bind alpha BGT at sites homologous with nAChR alpha subunits and that these subunits may confer differential ligand binding properties on the two alpha BGTBP subtypes of which they are components. PMID- 1869553 TI - Structure of the tetragonal surface virulence array protein and gene of Aeromonas salmonicida. AB - The paracrystalline surface protein array of the pathogenic bacterium Aeromonas salmonicida is a primary virulence factor with novel binding capabilities. The species-specific structural gene (vapA) for this array protein (A-protein) was cloned into lambda gt11 but was unstable when expressed in Escherichia coli, undergoing an 816-base pair deletion due to a 21-base pair direct repeat within the gene. However, the gene was stable in cosmid pLA2917 as long as expression was poor. A-protein was located in the cytoplasmic, inner membrane and periplasmic fractions in E. coli. The DNA sequence revealed a 1,506-base pair open reading frame encoding a protein consisting of a 21-amino acid signal peptide, and a 481-residue 50,778 molecular weight protein containing considerable secondary structure. When assembled into a paracrystalline protein array on Aeromonas the cell surface A-protein was totally refractile to cleavage by trypsin, but became trypsin sensitive when disassembled. Trypsin cleavage of the isolated protein provided evidence that both the NH2- and COOH-terminal regions form distinct structural domains, consistent with three-dimensional ultrastructural evidence. The NH2-terminal 274-residue domain remained refractile to trypsin activity. This segment connects by a trypsin and CNBr-sensitive 78 residue linker region to a COOH-terminal 129-residue fragment which could apparently refold into a partially trypsin-resistant structure after cleavage at residue 323. PMID- 1869554 TI - RPC19, the gene for a subunit common to yeast RNA polymerases A (I) and C (III). AB - Yeast RNA polymerases A (I) and C (III) share a subunit called AC19. The gene encoding AC19 has been isolated from yeast genomic DNA using oligonucleotide probes deduced from peptide sequences of the isolated subunit. This gene (RPC19) contains an intron-free open reading frame of 143 amino acid residues. RPC19 is a single copy gene that maps on chromosome II and is essential for cell viability. The amino acid sequence contains a sequence motif common to the Escherichia coli RNA polymerase alpha subunit, the Saccharomyces cerevisiae AC40 and B44.5 subunits, the human hRPB33 product, and the CnjC conjugation-specific gene product of Tetrahymena. The 5'-upstream region contains a sequence element, the PAC box, that has been conserved in at least 10 genes encoding subunits of RNA polymerases A and C. PMID- 1869555 TI - Glomerular basement membrane. Identification of dimeric subunits of the noncollagenous domain (hexamer) of collagen IV and the Goodpasture antigen. AB - The noncollagenous (NC1) domain hexamer of glomerular basement membrane (GBM) collagen is composed of a multiplicity of monomeric and dimeric subunits, and specific subunits are the targets for anti-GBM autoantibodies of patients with Goodpasture (GP) syndrome. The identity of GBM monomers has been established and the alpha 3(IV)NC1 monomer identified as the one that binds GP antibodies (Gunwar, S., Saus, J., Noelken, M. E., and Hudson, B. G. (1990) J. Biol. Chem. 265, 5466-5469). In the present study, the chain origin of 25 dimeric components and the identity of those that bound the anti-GBM antibodies from two GP patients were determined. This was accomplished by NH2-terminal sequence analysis and immunoblotting analysis of dimeric components that were resolved by two dimensional electrophoresis in combination with high pressure liquid chromatography. The results revealed that (a) the components are mainly homodimers of the NC1 domains of alpha 1, alpha 2, alpha 3, alpha 4, and probably alpha 5 chains of collagen IV, reflecting a specificity of promoter-promoter association and (b) each homodimer had several size and charge isoforms. The GP antibodies bound exclusively to both alpha 3(IV)NC1 monomers and dimers and not to other basement membrane constituents. These findings provided new insights about the structure of GBM collagen and together with our previous findings firmly established the alpha 3(IV) chain as the target for the anti-GBM antibodies that mediate glomerulonephritis and pulmonary hemorrhage in patients with Goodpasture syndrome. PMID- 1869556 TI - Secretion of N-glycosylated interleukin-1 beta in Saccharomyces cerevisiae using a leader peptide from Candida albicans. Effect of N-linked glycosylation on biological activity. AB - Human interleukin-1 beta (IL-1 beta) is expressed in activated monocytes as a 31 kDa precursor protein which is processed and secreted as a mature, unglycosylated 17-kDa carboxyl-terminal fragment, despite the fact that it contains a potential N-linked glycosylation site near the NH2 terminus (-Asn7-Cys8-Thr9-). cDNA coding for authentic mature IL-1 beta was fused to the signal sequence from the Candida albicans glucoamylase gene, two amino acids downstream from the signal processing site. Upon expression in Saccharomyces cerevisiae, approximately equimolar amounts of N-glycosylated (22 kDa) and unglycosylated (17 kDa) IL-1 beta protein were secreted. The N-glycosylated yeast recombinant IL-1 beta exhibited a 5-7 fold lower specific activity compared to the unglycosylated species. The mechanism responsible for inefficient glycosylation was also studied. We found no differences in secretion kinetics or processing between the two extracellular forms of IL-1 beta. The 17-kDa protein, which was found to lack core sugars, does not result from deglycosylation of the 22-kDa protein in vivo and does not result from saturation of the glycosylation enzymatic machinery through overexpression. Alteration of the uncommon Cys8 residue in the -Asn-X-Ser/Thr-glycosylation site to Ser also had no effect. However, increasing the distance between Asn7 and the signal processing site increased the extent of core N-linked glycosylation, suggesting a reduction in glycosylation efficiency near the NH2 terminus. PMID- 1869557 TI - Heparin strongly decreases the rate of inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. AB - Heparin depresses the second-order rate constant ka for the inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. High molecular mass heparin decreases ka from 1.3 x 10(7) M-1 s-1 to a limit of 4.6 x 10(4) M-1 s-1. Low molecular mass heparin is about 7-fold less effective. Dermatan sulfate and chondroitin sulfate are less efficient. Heparin preparations used in clinical care also strongly depress ka when tested at concentrations corresponding to their clinical efficacy. Heparin also decreases the ka for the elastase/eglin c and the cathepsin G/alpha 1-proteinase inhibitor systems but not that for the alpha 1-proteinase inhibitor/pancreatic elastase or trypsin pairs. These results, together with Sepharose-heparin binding studies, indicate that the ka-depressing effect of the polymer is related to its ability to form a tight complex with elastase but not with alpha 1-proteinase inhibitor. One mol of high molecular mass heparin binds 3 mol of neutrophil elastase with a Kd of 3.3 nM. Low molecular mass heparin binds elastase with a 1:1 stoichiometry and a Kd of 89 nM. For both heparins ka is lowest when elastase is fully saturated with heparin. From this we conclude that heparin decreases ka, because the heparin-elastase complex is able to slowly react with alpha 1-proteinase inhibitor and not because the inhibitor slowly dissociates the heparin-elastase complex. These findings may have important pathophysiological bearing. PMID- 1869558 TI - A novel regulatory element of the human alpha-globin gene responsible for its constitutive expression. AB - The alpha-globin gene is expressed at a constitutively high level upon gene transfer into both erythroid and nonerythroid cells. The beta-globin gene, on the other hand, is dependent on the presence of a linked viral enhancer for its efficient expression upon transfer into heterologous cells. In this report, we describe a novel regulatory element within the structural alpha-globin gene which can activate its own promoter to result in a high level of expression in both erythroid and non-erythroid cells. This regulatory element does not appear to have the properties of a classical enhancer. While this element exerts a positive effect on its own promoter, we have demonstrated in a previous study that the same element exerts a negative effect on heterologous genes such as the beta- and gamma-globin genes. In this study, we localize this element to a 259 nucleotide fragment immediately downstream from the translation initiation codon which is partially overlapped by a DNase I hypersensitive domain only in erythroid cells. We propose that this element may activate the alpha-globin gene promoter in all cell types in vivo as it does in vitro. The specificity of erythroid expression of the alpha-globin gene in vivo is probably determined by a "permissive" chromatin configuration in erythroid cells and a "nonpermissive" configuration in non-erythroid cells. PMID- 1869559 TI - Direct effects of platelet-activating factor on isolated rat osteoclasts. Rapid elevation of intracellular free calcium and transient retraction of pseudopods. AB - Platelet-activating factor (PAF, 1-O-alkyl-(2R)-acetylglycero-3-phosphocholine) is a potent inflammatory mediator whose actions on bone cells have not been investigated previously. In this study, we examined effects of PAF on osteoclast morphology and intracellular free calcium. Osteoclasts, the large multinucleated cells responsible for bone resorption, were isolated from neonatal rat long bones, and the cytosolic free calcium concentration ([Ca2+]i) of individual fura 2-loaded cells was monitored by microspectrofluorimetry. In one series of experiments, PAF was applied focally to single, isolated osteoclasts (1 nM to 1 microM racemic mixture, in an application micropipette). Within 10 s of PAF application, [Ca2+]i increased from basal levels of 74 +/- 6 nM to peak levels of 209 +/- 28 nM (mean +/- S.E. of 24 cells responding). These results indicate that PAF acted directly on osteoclasts. In more than 75% of cells tested, PAF, at concentrations greater than or equal to 10 pM (final concentration, in the bath), induced biphasic elevation of [Ca2+]i. This response was highly specific for PAF, in that vehicle, lyso-PAF (the biologically inactive precursor/metabolite of PAF), and (S)-PAF (the inactive enantiomer of PAF) all failed to change [Ca2+]i. Moreover, [Ca2+]i elevation was blocked by the specific PAF antagonist CV-3988. To determine the source of Ca2+, cells were bathed in Ca(2+)-free medium, where PAF still caused an increase in [Ca2+]i, establishing that the response to PAF arose, at least in part, by release of Ca2+ from internal stores. In addition to changes in [Ca2+]i, PAF caused retraction followed by respreading of peripheral pseudopods. These findings indicate that rat osteoclasts respond to PAF by release of internal calcium and alterations in cell morphology and suggest that PAF may regulate resorption in inflammatory bone diseases. PMID- 1869560 TI - Sulfated glycolipids are the platelet autoantigens for human platelet-binding monoclonal anti-DNA autoantibodies. AB - The human monoclonal autoantibody HF2-1/17, produced by a human-human hybridoma derived from lymphocytes of a lupus patient with thrombocytopenia, reacts with single stranded DNA and platelets. To determine the chemical nature of the autoantigen against which this antibody is directed on platelets, this platelet antigen was purified by the lipid extraction of sonicated platelets, DEAE Sephadex chromatography, and high performance liquid chromatography. The purified glycolipids, a trace component in platelets, demonstrated high reactivity with the HF2-1/17 antibody using a competition enzyme-linked immunosorbent assay system or immunostaining of thin layer chromatograms. The purified glycolipids co migrated with bovine sulfatides by thin layer chromatography. The purified glycolipids contain sulfate and galactose but not sialic acid or phosphate. Fast atom bombardment-mass spectrometry revealed these sulfatides to be sulfated monohexyl ceramides. The dominant species has a molecular weight of 794 while a minor form has a molecular weight of 812 due to an extra hydroxyl group and loss of a double bond. These results indicate that the platelet autoantigen against which the human monoclonal anti-DNA antibody is directed represents a family of novel monogalactosyl sulfatides. PMID- 1869561 TI - The interfaces of actin and Acanthamoeba actobindin. Identification of a new actin-binding motif. AB - Actobindin is an 88-amino acid polypeptide, containing two almost identical repeated domains of 33 and 34 residues. Depending on the molar ratios in which they are mixed, actobindin binds either one or two actin molecules. We cross linked actobindin and actin in the 1:1 complex, using the zero-length cross linker 1-ethyl-3(3-dimethylaminopropyl)carbodiimide. The cross-linked peptides were purified after consecutive CNBr cleavage and trypsin and Staphylococcus protease V8 digestions, and the cross-linked side chains were identified by amino acid sequencing. Isopeptide linkages were formed between residues Glu-100 of actin and Lys-16 of actobindin. In addition, we found a connection between one or more of the acidic residues 1,2, or 3 of actin and Lys-16 and Lys-52 of actobindin. The cross-linked regions in actobindin contain Leu-Lys-His-Ala-Glu Thr motifs, similar to sequences observed in several other actin-binding proteins. PMID- 1869562 TI - A Dictyostelium discoideum cellulase is a member of a spore germination-specific gene family. AB - A member of the 270 spore germination-specific gene family in Dictyostelium discoideum is shown to encode a cellulase (endo-(1,4)-beta-D-glucanase, EC 3.2.1.4) activity. The 270-6 deduced protein shows 38% identity and 58% similarity to an avocado (Persea americana) cellulase. During spore germination in Dictyostelium extracellular cellulase activity starts to accumulate coincident with the appearance of the 270-6 gene transcript. Amoebae transformed by a vector containing the 270-6 mRNA sequence express an extracellular cellulase during vegetative growth when there would otherwise be no cellulase activity. In addition, the expression of a truncated 270-6 polypeptide lacking the 270 gene family-defining tetrapeptide repeat and the C-terminal region, in suitably transformed amoebae, also produces an extracellular cellulase activity. Several differently sized cellulase activities are shown to accumulate during spore germination, and it is possible that the 270 gene family represents a coordinately expressed family of cellulases. PMID- 1869563 TI - Procathepsins L and D are membrane-bound in acidic microsomal vesicles. AB - Procathepsins L and D, the proenzyme forms of two lysosomal proteases, are shown to bind to mouse fibroblast microsomal membranes at acidic pH. The propeptide of procathepsin L is necessary for membrane association because the mature forms of this lysosomal protein did not bind to the membranes. Both proenzymes were eluted from the membranes by increasing either the pH or the ionic strength of the buffer, so they are peripheral proteins that interact ionically with the membranes. The proenzymes were not eluted from the membranes with 50 mM mannose or 10 mM mannose 6-phosphate, which suggests that carbohydrate does not mediate membrane binding. Membrane binding is probably a specific, protein-mediated interaction since treatment of the microsomes with trypsin reduced by half the amount of procathepsin L which bound to the membranes, and binding of procathepsin L to the membranes was saturable. One or more "lysosomal proenzyme receptors" capable of binding to lysosomal proenzymes at acidic pH could complement the mannose 6-phosphate receptor system in prelysosomes and sort certain lysosomal proenzymes to lysosomes. PMID- 1869564 TI - Mitochondrial import and processing of rat liver carnitine palmitoyltransferase II defines the amino terminus of the mature protein. Possibility of differential modification of the rat and human isoforms. AB - [35S]Methionine-labeled porcine heart citrate synthase (used here as a positive control) and rat liver carnitine palmitoyltransferase II (CPT II) were generated by in vitro transcription and translation of their cDNA constructs in appropriate Bluescript plasmids. Each product was imported into rat liver mitochondria in an energy-dependent manner to yield an immunoprecipitable protein of smaller size that comigrated with the corresponding purified enzyme. The size shift occurring with citrate synthase was consistent with the removal of the postulated 27-amino acid leader peptide. To determine the amino terminus of mature CPT II, [35S]methionine- or [3H]leucine-labeled material (after import and processing) was subjected to Edman degradation, followed by counting of the radioactivity released on each cycle. The results established that the precursor targeting peptide was cleaved between leucine 25 and serine 26 in the previously deduced amino acid sequence. Taken in conjunction with the recent report of Finocchiaro et al. (Finocchiaro, G., Taroni, F., Rocchi, M., Martin, A. L., Colombo, I., Tarelli, G. T., and DiDonato, S. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 661 665), the present results establish three key points concerning the rat and human forms of CPT II. First, it appears that in both species the initial translation product contains 658 amino acids and, upon mitochondrial import, is reduced in length by 25 residues through cleavage at an identical site. Second, the difference in electrophoretic mobility between the two mature proteins (documented earlier) presumably reflects either anomalous behavior of one of them on polyacrylamide gels or differential covalent modification. Finally, the recent suggestion by Brady et al. (Brady, P. S., Liu, J. S., Park, E. A., Hanson, R. W., and Brady, L. J. (1991) FASEB J. 5, A817) that our CPT II cDNA construct is incomplete in the 5'-coding region is refuted. PMID- 1869565 TI - The upstream stimulatory factor binds to and activates the promoter of the rat class I alcohol dehydrogenase gene. AB - The gene encoding rat class I alcohol dehydrogenase (ADH) is expressed primarily in the liver. Recent studies in our laboratories indicate that multiple cellular factors present in the rat liver interact with various regions of the promoter of this gene. One of the regions contains the sequence 5'-CACATG-3' that has an "E box" homology to which a number of transcription factors containing the basic helix-loop-helix motif bind. We now demonstrate that the human transcription factor, upstream stimulatory factor (USF), a basic helix-loop-helix-containing protein, binds to and activates the promoter of the rat class I ADH gene. Electrophoretic mobility shift assays of labeled oligonucleotide containing the 5'-CACATG-3' sequence within the ADH promoter revealed the formation of multiple DNA-protein complexes when nuclear extracts obtained from adult rat liver were used. The binding of proteins to the DNA could be competed away with an oligonucleotide specifying a sequence within the adenovirus major late promoter (MLP) that had previously been shown to bind USF. Similar complexes were observed when electrophoretic mobility shift assays of labeled MLP oligonucleotide were performed with rat liver nuclear extracts. Conversely, nuclear extracts isolated from HeLa cells, cells known to have abundant USF, contain factors that interact with the sequence present in the ADH promoter. This interaction could be competed efficiently by the MLP oligonucleotide. USF synthesized in an in vitro transcription and translation system also binds to the ADH promoter as well as to the MLP. In addition, antiserum directed against USF recognizes factors present in the rat liver nuclear extracts that interact with the ADH promoter. Furthermore, transcription directed from both the ADH and the adenovirus major late promoters was inhibited by an oligonucleotide representing the USF-binding site within the ADH promoter in a cell-free in vitro transcription system. Lastly, an ADH promoter-reporter gene construct was transactivated by an eukaryotic expression vector containing USF in HepG2 cells co-transfected with the two constructs. These experiments demonstrate that USF is present in the rat liver and that it binds to and activates the promoter of the rat class I ADH gene in a sequence-specific manner. PMID- 1869566 TI - Proteoglycan synthesis and metabolism by mouse uterine stroma cultured in vitro. AB - Chondroitin sulfate proteoglycans (CSPGs) and hyaluronate have been identified as the predominant glycoconjugates synthesized and secreted by mouse uterine stromal cells (USC) cultured in vitro. CSPGs in both the cell-associated and secreted fractions have identical characteristics with regard to anion exchange chromatographic behavior, sensitivity of the intact molecules and constituent glycosaminoglycans to a variety of chemical and enzymatic digestions, lack of interaction with hydrophobic affinity resins, and density (greater than 1.46 g/ml). Chase labeling studies indicated a metabolic half-life of cell-associated, [35S]sulfate-labeled macromolecules of 5-6 h. Once secreted, CSPGs did not appear to be degraded or endocytosed to a significant extent. In contrast, a large fraction (50%) of the cell-associated CSPGs were degraded to low Mr (less than 3000) products via a chloroquine-sensitive pathway. Studies of the kinetics of intracellular transport indicated that approximately 30 min were required for CSPG core proteins to move from the rough endoplasmic reticulum to the Golgi apparatus and 15-20 min to move from the Golgi to the cell surface, i.e. protease accessible compartment. There was no significant lag period between the time CSPGs first arrived at the cell surface and the time at which they were first detectable in the medium. Examination of CSPG expression during USC differentiation in utero or in vitro demonstrated that these molecules were produced with similar efficiency by USC under both conditions. Collectively, these studies provide the first comprehensive description of proteoglycan production and metabolism in USC, a uterine cell type intimately involved with embryo implantation processes. Potential functions for CSPGs and hyaluronate as modulators of embryo invasive processes and uterine expansion are proposed. PMID- 1869567 TI - Purification and partial sequencing of saxiphilin, a saxitoxin-binding protein from the bullfrog, reveals homology to transferrin. AB - Plasma from the bullfrog, Rana catesbeiana, contains a soluble component of unknown function that specifically binds the neurotoxin, [3H]saxitoxin, with a Kd of approximately 0.2 nM. Saxiphilin, the protein responsible for this activity, was purified approximately 440-fold from bullfrog plasma by column chromatography on heparin-Sepharose followed by chromatofocusing. The purified saxiphilin preparation exhibits a binding capacity of 9.6 nmol/mg protein and a Kd of 0.32 nM for [3H]saxitoxin. Analysis of the preparation by sodium dodecyl sulfate polyacrylamide gel electrophoresis shows a predominant band migrating with an apparent Mr of approximately 89,000 which is similar to the expected size of saxiphilin previously estimated by nondenaturing size exclusion chromatography. Amino-terminal sequencing of the approximately 89-kDa protein and sequencing of four different tryptic peptide fragments revealed that each of the partial saxiphilin sequences can be aligned by homology with members of the transferrin protein family with sequence identity as high as 69%. The available sequence corresponding to conserved residues that comprise part of the two Fe3+ binding sites in lacto-transferrin show several substitutions in saxiphilin, suggesting that saxiphilin is not an Fe(3+)-binding protein. Saxiphilin appears to be a monomeric approximately 89-kDa protein that is evolutionarily related to transferrin but which binds saxitoxin instead of Fe3+. PMID- 1869568 TI - Crystal structure of Escherichia coli CheY refined at 1.7-A resolution. AB - The three-dimensional structure of wild-type CheY from Escherichia coli has been refined by stereochemically restrained least squares minimization to a crystallographic R-factor of 15.1% at 1.7-A resolution. The structure contains 1165 atoms, including all atoms of the protein, 147 water molecules, and three sulfate ions. The final model has root mean square deviations of 0.018 and 0.049 A from idealized bond lengths and angle distances, respectively. Seven amino acid side chains have been modeled in dual conformations. CheY folds as a compact (beta/alpha)5 globular protein, with the phosphorylation region contained in a cavity on one face of the molecule. This active site area is bordered by the carboxyl termini of the three central beta-strands, by alpha 1, and by the loop connecting beta 5 to alpha 5. The Lys-109 side chain of this loop extends into the active site by virtue of its cis peptide bond conformation preceding Pro-110. The epsilon-amino group of Lys-109 is in close bonding contact with the carboxyl group of Asp-57, the residue that is phosphorylated in the activation process of CheY. The details of the hydrogen bonding network in the phosphorylation region indicate that structural rearrangements must accompany the phosphorylation of Asp 57. PMID- 1869569 TI - Purification of retinol dehydrogenase from bovine retinal rod outer segments. AB - We purified retinol dehydrogenase from bovine rod outer segments using polyethylene glycol precipitation and hydroxylapatite, concanavalin A-Sepharose CL-4B, and Sepharose CL-6B column chromatography in the presence of NADP. We obtained 13-fold purification of retinol dehydrogenase with specific activity of 61.8 nmol/min/mg and 3.8% recovery. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that retinol dehydrogenase had a molecular mass of 37,000 daltons. The Km values of purified retinol dehydrogenase for all-trans retinol and all-trans retinal were 6.6 mM and 0.085 mM, respectively. The purified enzyme reacted with the all-trans retinal but not with 13-, 11-, and 9 cis compounds. In addition, we prepared antibody to retinol dehydrogenase using rat. The anti-retinol dehydrogenase antibody precipitated retinol dehydrogenase activity and was confirmed to bind to 37-kDa protein by Western blotting. We also found that anti-retinol dehydrogenase antibody bound to bovine rod outer segments specifically by immunohistochemical technique. The molar ratio of retinol dehydrogenase to opsin in rod outer segments estimated by enzyme-linked immunosorbent assay was 1:140. PMID- 1869570 TI - The transmembrane topology of the amino terminus of the alpha subunit of the nicotinic acetylcholine receptor. AB - We have investigated the transmembrane topology of the amino-terminal domain of the alpha subunit of the mouse muscle nicotinic acetylcholine receptor synthesized in vitro and in vivo. Using oligonucleotide-directed mutagenesis we introduced new glycosylation consensus sequences at alpha 154 and at alpha 200. For each novel site, additional constructs were made in which the original site at alpha N141 was eliminated. Glycosylation at the new sites, as exhibited in a rabbit reticulocyte cell-free translation system supplemented with canine pancreatic microsomes and in a transient transfection system with COS cells, was taken as evidence of the transmembrane translocation of the new site. Each of the new sites was glycosylated in both systems. In separate experiments we found that an alpha subunit fragment terminating at alpha M207 could be extracted from microsomal membranes with sodium carbonate after in vitro translation, indicating that this fragment is not an integral membrane protein. Our results, taken together with previous experiments, indicate that the amino terminus of the alpha subunit up to at least residue alpha 207 is translocated across the membrane of the endoplasmic reticulum. This topology probably represents the orientation of the amino terminus of the alpha subunit in the assembled receptor. PMID- 1869571 TI - Promoter DNA contacts made by the vaccinia virus early transcription factor. AB - Vaccinia virus RNA polymerase requires the heterodimeric protein, vaccinia early transcription factor (VETF), for transcription of early gene templates in vitro. We have analyzed the vaccinia growth factor promoter sequences interacting with VETF at the nucleotide level and provide evidence that the factor contacts the DNA at two separate sites. DNase I protection analysis showed that VETF was found to nucleotides -12 to -29 relative to the transcription initiation site, and also to nucleotides +8 to +10 downstream of the initiation site. The importance of both binding sites for stable complex formation was supported by methylation interference analysis. Using synthetic oligonucleotides encoding different parts of the vaccinia growth factor promoter, it was shown that nucleotides down-stream of the transcription initiation site are required for stable complex formation. Competition binding experiments demonstrated that only the upstream binding site contributes significantly to binding specificity. Binding to two separated DNA sequences results in a bend in the promoter DNA as demonstrated by electrophoretic mobility shift analysis of permuted DNA fragments. These findings suggest that VETF activates transcription by sequence specific binding and structural alteration of the promoter DNA helix. PMID- 1869572 TI - A role for ATP hydrolysis in vaccinia virus early gene transcription. Dissociation of the early transcription factor-promoter complex. AB - Vaccinia virus RNA polymerase requires the vaccinia early transcription factor, VETF, for the in vitro initiation of transcription at early gene promoters in a reaction requiring ATP hydrolysis. VETF binds specifically to early gene promoters and has an associated DNA-dependent ATPase activity. The effect of ATP on the interaction of VETF with the promoter for the vaccinia growth factor gene promoter has been examined. ATP had no marked effect on the steady-state level of promoter binding but dramatically affected the kinetics of dissociation of VETF from the promoter. The half-life of the VETF-promoter complex was greatly reduced in the presence of ATP. The destabilization of the complex was specific for ATP and dATP, consistent with the substrate specificity of the VETF-associated ATPase. ADP or the non-hydrolyzable ATP analog adenylyl-imidodiphosphate did not destabilize the complex suggesting that ATP hydrolysis is obligatory for dissociation. These findings provide a link between the promoter binding and ATPase activities associated with VETF and suggest that the ATP-dependent dissociation of the VETF-promoter complex is an important event in the transcription of vaccinia virus early genes. PMID- 1869573 TI - Cloning and characterization of a Saccharomyces cerevisiae gene encoding a new member of the ubiquitin-conjugating protein family. AB - Ubiquitin-conjugating enzymes (E2s), which participate in the post-translational conjugation of ubiquitin to proteins, are encoded by a multigene family in the yeast Saccharomyces cerevisiae. E2s function in a variety of cellular activities including intracellular proteolysis, DNA repair, sporulation, and cell cycle traverse. Here, we report the cloning and characterization of a new member of the yeast UBC gene family, UBC8. UBC8 encodes a 206-amino acid protein containing a highly acidic carboxyl terminus. The primary structure of the protein is similar to that of all other known E2s, with the highest homology being to the E2 (23 kDa) of wheat germ. Haploid strains in which the UBC8 gene is disrupted are viable, and the disruption does not produce any obvious phenotype. The UBC8 protein, produced in Escherichia coli, forms thiol ester adducts with ubiquitin and, apparently, diubiquitin, but does not transfer ubiquitin to histones. PMID- 1869575 TI - Preparation of thermo-responsive membranes. II. AB - Two types of liquid crystal (LC)-immobilized membranes were prepared by a soaking method and sandwich method to control the permeation of indomethacin, as a model drug, in response to local and systemic fever. Monooxyethylene trimethylolpropane tristearate (MTTS) was used as a model LC because it has a gel-liquid crystal phase transition temperature near the body temperature, 39-40 degrees C in phosphate buffered saline (pH 7.4). Two porous polypropylene (PP) membranes were soaked into 20% MTTS chloroform solution in the soaking method, and two PP membranes were poured with the melted MTTS and pressed in the sandwich method. Thermo-response efficacy of the soaked membrane was dependent upon the content of MTTS in MTTS membrane, and the MTTS content above the void volume of PP membrane (38%) was needed for high efficacy. On the other hand, the sandwich membrane exhibited higher thermo-response efficacy than the soaked membrane, because more LC was embedded in the pores of sandwich membrane than that of the soaked membrane. The sandwich membrane permeation of indomethacin was sharply controlled by temperature changes between 32 and 38 degrees C. PMID- 1869574 TI - Negative cilia concept for thromboresistance: synergistic effect of PEO and sulfonate groups grafted onto polyurethanes. AB - In order to investigate the interaction between various sulfonated polyurethanes (PUs) and blood, a commercial PU surface was chemically modified by poly(ethylene oxide) (PEO), dodecanediol(DDO), and propane sultone to give hydrophilic, hydrophobic, and negative sulfonated surfaces, respectively. The blood compatibility of modified PUs was evaluated by an in vitro platelet adhesion test, activated partial thromboplastin time (APTT), and prothrombin time (PT) measurements as well as an ex vivo rabbit A-A shunt method. In the platelet adhesion test, the hydrophilic PEO grafted PUs showed less platelet adhesion than untreated PU and hydrophobic DDO grafted PU. Sulfonated PU-PEO exhibited a lower degree of adhesion and shape change of platelet. The APTT and PT, especially APTT, of the sulfonated PUs were extended, whereas those of PU-PEO and PU-DDO did not show any significant change compared with untreated PU. Meanwhile, in the ex vivo experiment, hydrophilic PEO grafted PUs showed longer occlusion times than untreated PU or hydrophobic DDO grafted PU. In addition, the incorporation of SO3 groups at the end of PU-DDO and PU-PEO, particularly PU-PEO-SO3, exhibited an enormous prolongation in occlusion time, indicating a synergistic effect of the hydrophilic PEO and the negative SO3 groups on thromboresistance. These occlusion times corresponded well to in vitro evaluation results: the less adhesion and shape change of platelet and the longer APTT and PT, the more extended the ex vivo occlusion time. PMID- 1869576 TI - A study of the fatigue properties of small diameter wires used in intramuscular electrodes. AB - Single and multi-strand stainless steel and cobalt-nickel alloy wires, with strand diameters from 26 to 46 microns, were fatigue tested using a modified rotating bending test to determine what factors are most important in controlling fatigue life. The relation between cyclic strain and cyclic life was determined for each material by cyclically straining test specimens at various strain ranges and recording the number of cycles to failure. The results show that (a) the fatigue curves of the 316LVM, MP35N, DBS, and Syntacoben wires are very similar and have many of the same fatigue characteristics of specimens of large cross section. (b) Multi-stranded wires have the same average fatigue life as their individual constituent strands, but the variance of that life is smaller. (c) Deformities in the wire, which are created during the manufacturing, appear to have the effect of shortening the fatigue life of these small section wires. (d) Observation of wire fracture surfaces show a relatively small crack propagation zone and a large fast fracture zone suggesting that most of the fatigue life of these small wires is in the original crack formation, which creates a large stress concentration and quickly leads to wire failure. (e) The size of the wire cross sectional area is of secondary importance compared to the amplitude of the maximum cyclic strain of the individual strands in determining fatigue life of the cable. To maximize the fatigue life of electrodes in vivo, the highest fatigue life for a given bending radius of curvature is desired. This suggests wire strands should be manufactured at the smallest diameter possible (without introducing structural flaws) to maximize service life. PMID- 1869577 TI - Use of a phosphophoryn-Ca(+2)-collagen composition that mimics a mineralization front in unicortical defects in long bones. AB - The present study was designed to ascertain if dynamic ionic matrices that mimic the mineralization front could be used as active scaffolds for bone repair. Dentinal phosphophoryn calcium salts were extracted from unerupted bovine dentine using chatopic buffers and EDTA. The phosphophoryns were subsequently isolated following precipitation with CaCl2. The phosphophoryn-Ca+2 salts were then mixed with pepsin solubilized bovine skin collagen and lyophilized into hardened sponges. Three groups of 4 beagle dogs were employed such that one leg served as an experimental test site for a mechanical wound, while the contralateral leg served as a control. Animals were sacrificed at 1,3, and 6 month intervals. The test specimens were harvested, fixed, and processed for routine histology, examined with image histomorphometric analysis, and scored. Tabulation of these data indicated that phosphophoryn-Ca(+2)-collagen enhances the repair of mechanically formed osseous defects in the distal femur of beagle dogs. This enhanced rate of bone repair was manifest by earlier filling of bony voids with osteoid and trabecular bone. Eventually, this process was followed by recortification of the surface defects. These data suggest that components derived from a mineralization front may influence bone formation in unicortical defects within long bones. PMID- 1869578 TI - Immunomodulating effects of serum-material interactions. AB - The objective of this study is to evaluate an in vitro model to assess the effects of serum-material interactions on complement activation, macromolecular adsorption, and lymphocyte response. Minifilters of clinically available materials (PVA, EVAL-4A, and EVAL-D) used in extracorporeal therapies were evaluated. The test circuit consisted of a pump, sterile tubing, collection vessels, and the minifilter. A sham circuit similar to the test circuit was constructed, but without the filter. Serum flow rates and volumes processed were scaled down to those of clinical use. Post PVA serum showed the highest degree of complement activation, macromolecular solute adsorption, and lymphocyte suppressive response when incubated with Con-A, PHA, PWM, and Candida. Post EVAL 4A sera enhanced the response of lymphocytes to Con-A and PHA, while Post EVAL-D sera showed a slight suppression to these mitogens. Blood-material interactions have been shown to cause blood cellular changes. The in vitro model employed is simple to apply and does not require an animal or patient. The membrane modules used are a mini-type of clinically available extracorporeal filters, and there is a greater direct relevancy to clinical applications than there would be using specially formulated materials. This system would provide useful preclinical information in evaluating the effect of serum-material interactions. PMID- 1869579 TI - Macrophage activation induced by different carbon fiber-epoxy resin composites. AB - The activation of cells by interaction with solid surfaces is important in many settings, including the response of tissue to implanted materials. However, few comprehensive studies of both cell migration and activation have been performed so that the connection between these events and immunological activation against foreign material is not well understood. In the present study, synthesis and expression of Ia antigens by peritoneal exudate macrophages after implantation of different carbon fiber composites in the rat peritoneal cavity have been investigated in order to determine whether the type of material implanted affected the composition of Ia-bearing cells of the exudate. The results have confirmed the low level of expression of Ia on resident peritoneal macrophages; while we have found that macrophages, harvested after implantation, express a different amount of Ia related to the different cure cycles of the composite material used. PMID- 1869580 TI - In vitro tendon cell growth rates on a synthetic fiber scaffold material and on standard culture plates. AB - Growth rates of rat tendon fibroblasts cultured in a three-dimensional carbon fiber matrix were compared with those of cells cultured on standard flat culture plates. The carbon fiber has been used as a tissue scaffold for tendon and ligament repair in animal and clinical studies. While cell growth on the culture plates appears to follow a growth curve containing a lag phase, a log phase, and plateau phase of growth, cell growth in the fiber matrix was characterized by a suppressed log phase of growth. SEM and cytotoxicity studies indicated that this effect was not caused by growth-inhibiting or cytotoxic substances from the carbon fiber. While we cannot rule out the possibility that cell growth was influenced by the surface chemistry of the carbon substrate, evidence from this and other studies suggests that the observed effect was caused by a lack of readily available surface area for cell attachment and growth on the small fibers. Because cell colonies growing on individual fibers are limited (at least in theory) to growing in two directions only, they enjoy limited opportunities for cell migration and growth--in contrast with cell colonies on flat culture plates. These results suggest fundamental differences in the mechanisms controlling cell growth on planar vs. three-dimensional fiber substrates. PMID- 1869581 TI - A physicochemical study of the morphology of progesterone-loaded microspheres fabricated from poly(D,L-lactide-co-glycolide). AB - Progesterone-loaded microspheres are fabricated by a solvent evaporation process from a poly(D,L-lactide-co-glycolide) (85/15 PLG) and from alpha-progesterone. Methylene chloride is used as solvent and polyvinyl alcohol and methylcellulose are used as surfactants. The microspheres are characterized by scanning electron microscopy, differential scanning calorimetry, and x-ray powder diagrams. Our study shows that the morphology and the thermal behavior of PLG microspheres can vary significantly with progesterone loading and sample thermal history. Below and at 16.5% loading the microspheres exhibit a smooth outer surface. Above 23% loading, the surface becomes rough, embedded by copolymer particles or well defined crystals. Pores and cracks can also be observed. Below 35% the progesterone is molecularly dispersed. At 35% and above crystal domains of the steroid appear and two crystalline forms are found: alpha- and beta-progesterone. The physical state of progesterone and the nature of its crystal domains dispersed in the PLG matrix can change during storage. Also a progressive development of an endothermic peak at the Tg event of the copolymer is observed during storage. No well defined relationship of peak size to progesterone loading can be shown. PMID- 1869582 TI - Effects of fibroblasts and basic fibroblast growth factor on facilitation of dermal wound healing by type I collagen matrices. AB - Healing of large open dermal wounds is associated with decreased values of the tensile strength even up to 6 months post-wounding. Results of previous studies have shown that healing is facilitated in the presence of a type I collagen sponge by promoting deposition of newly synthesized large-diameter collagen fibers parallel to the fibers of the sponge. In this study healing is evaluated in dermal wounds treated with a collagen sponge seeded with fibroblasts or coated with basic fibroblast growth factor (bFGF). Experimental results indicate that the presence of a collagen sponge results in increased wound tensile strength and increased collagen fiber diameters in the upper dermis 15 days post-wounding in an excisional guinea pig dermal wound model. In comparison, dermal wounds treated with collagen sponges seeded with fibroblasts or coated with bFGF showed increased tensile strengths 15 days postimplantation and increased degree of reepithelialization. These results indicate that fibroblast seeding and bFGF coating in conjunction with a type I collagen sponge matrix facilitate early dermal and epidermal wound healing. PMID- 1869583 TI - Characterization of YDJ1: a yeast homologue of the bacterial dnaJ protein. AB - The YDJ1 (yeast dnaJ) gene was isolated from a yeast expression library using antisera made against a yeast nuclear sub-fraction termed the matrix lamina pore complex. The predicted open reading frame displays a 32% identity with the sequence of the Escherichia coli heat shock protein dnaJ. Localization of YDJ1 protein (YDJ1p) by indirect immunofluorescence reveals it to be concentrated in a perinuclear ring as well as in the cytoplasm. YDJ1p cofractionates with nuclei and also microsomes, suggesting that its perinuclear localization reflects association with the ER. YDJ1p is required for normal growth and disruption of its gene results in very slow growing cells that have pleiotropic morphological defects. Haploid cells carrying the disrupted YDJ1 gene are inviable for growth in liquid media. We further show that a related yeast protein, SIS1, is a multicopy suppressor of YDJ1. PMID- 1869584 TI - Ribosome binding to the endoplasmic reticulum: a 180-kD protein identified by crosslinking to membrane-bound ribosomes is not required for ribosome binding activity. AB - We have used the membrane-impermeable, thiol-cleavable, crosslinker 3,3'-dithio bis (sulfosuccinimidylpropionate) to identify proteins that are in the vicinity of membrane-bound ribosomes of the RER. A specific subset of RER proteins was reproducibly crosslinked to the ribosome. Immunoblot analysis of the crosslinked products with antibodies raised against signal recognition particle receptor, ribophorin I, and the 35-kD subunit of the signal sequence receptor demonstrated that these translocation components had been crosslinked to the ribosome, but each to a different extent. The most prominent polypeptide among the crosslinked products was a 180-kD protein that has recently been proposed to be a ribosome receptor (Savitz, A.J., and D.I. Meyer, 1990. Nature (Lond.). 346: 540-544). RER membrane proteins were reconstituted into liposomes and assayed with radiolabeled ribosomes to determine whether ribosome binding activity could be ascribed to the 180-kD protein. Differential detergent extraction was used to prepare soluble extracts of microsomal membrane vesicles that either contained or lacked the 180 kD protein. Liposomes reconstituted from both extracts bound ribosomes with essentially identical affinity. Additional fractionation experiments demonstrated that the bulk of the ribosome binding activity present in detergent extracts of microsomal membranes could be readily resolved from the 180-kD protein by size exclusion chromatography. Taken together, we conclude that the 180-kD protein is in the vicinity of membrane bound ribosomes, yet does not correspond to the ribosome receptor. PMID- 1869585 TI - Determinants for cleavage of the chlorophyll a/b binding protein precursor: a requirement for a basic residue that is not universal for chloroplast imported proteins. AB - We demonstrate that the precursor of the major light-harvesting chlorophyll a/b binding protein (LHCP of Photosystem II), encoded by a Type I gene, contains distinct determinants for processing at two sites during in vitro import into the chloroplast. Using precursors from both pea and wheat, it is shown that primary site processing, and release of a approximately 26-kD peptide, depends on an amino-proximal basic residue. Substitution of an arginine at position -4 resulted in an 80% reduction in processing, with the concomitant accumulation of a high molecular weight intermediate. Cleavage occurred normally when arginine was changed to lysine. The hypothesis that a basic residue is a general requirement for transit peptide removal was tested. We find that the precursors for the small subunit of Rubisco and Rubisco activase do not require a basic residue within seven amino acids of the cleavage site for maturation. In the wheat LHCP precursor, determinants for efficient cleavage at a secondary site were identified carboxy to the primary site, beyond what is traditionally called the transit peptide, within the sequence ala-lys-ala-lys (residues 38-41). Introduction of this sequence into the pea precursor, which has the residues thr thr-lys-lys in the corresponding position, converted it to a substrate with an efficiently recognized secondary site. Our results indicate that two different forms of LHCP can be produced with distinct NH2-termini by selective cleavage of a single precursor polypeptide. PMID- 1869587 TI - MPS1 and MPS2: novel yeast genes defining distinct steps of spindle pole body duplication. AB - It is crucial to the eucaryotic cell cycle that the centrosome undergo precise duplication to generate the two poles of the mitotic spindle. In the budding yeast Saccharomyces cerevisiae, centrosomal functions are provided by the spindle pole body (SPB), which is duplicated at the time of bud emergence in G1 of the cell cycle. Genetic control of this process has previously been revealed by the characterization of mutants in CDC31 and KAR1, which prevent SPB duplication and lead to formation of a monopolar spindle. Newly isolated mutations described here (mps1 and mps2, for monopolar spindle) similarly cause monopolar mitosis but their underlying effects on SPB duplication are unique. The MPS1 gene is found by electron microscopy to be essential for proper formation of the site at which the new SPB normally arises adjacent to the existing one. By contrast, a mutation in MPS2 permits duplication to proceed, but the newly formed SPB is structurally defective and unable to serve as a functional spindle pole. Distinct temporal requirements for the CDC31, MPS1, and MPS2 gene functions during the SPB duplication cycle further demonstrate the individual roles of these genes in the morphogenetic pathway. PMID- 1869586 TI - Three-dimensional structure of myosin subfragment-1 from electron microscopy of sectioned crystals. AB - Image analysis of electron micrographs of thin-sectioned myosin subfragment-1 (S1) crystals has been used to determine the structure of the myosin head at approximately 25-A resolution. Previous work established that the unit cell of type I crystals of myosin S1 contains eight molecules arranged with orthorhombic space group symmetry P212121 and provided preliminary information on the size and shape of the myosin head (Winkelmann, D. A., H. Mekeel, and I. Rayment. 1985. J. Mol. Biol. 181:487-501). We have applied a systematic method of data collection by electron microscopy to reconstruct the three-dimensional (3D) structure of the S1 crystal lattice. Electron micrographs of thin sections were recorded at angles of up to 50 degrees by tilting the sections about the two orthogonal unit cell axes in sections cut perpendicular to the three major crystallographic axes. The data from six separate tilt series were merged to form a complete data set for 3D reconstruction. This approach has yielded an electron density map of the unit cell of the S1 crystals of sufficient detail. to delineate the molecular envelope of the myosin head. Myosin S1 has a tadpole-shaped molecular envelope that is very similar in appearance to the pear-shaped myosin heads observed by electron microscopy of rotary-shadowed and negatively stained myosin. The molecule is divided into essentially three morphological domains: a large domain on one end of the molecule corresponding to approximately 60% of the total molecular volume, a smaller central domain of approximately 30% of the volume that is separated from the larger domain by a cleft on one side of the molecule, and the smallest domain corresponding to a thin tail-like region containing approximately 10% of the volume. This molecular organization supports models of force generation by myosin which invoke conformational mobility at interdomain junctions within the head. PMID- 1869588 TI - Assembly of the mammalian muscle acetylcholine receptor in transfected COS cells. AB - We have investigated the mechanisms of assembly and transport to the cell surface of the mouse muscle nicotinic acetylcholine receptor (AChR) in transiently transfected COS cells. In cells transfected with all four subunit cDNAs, AChR was expressed on the surface with properties resembling those seen in mouse muscle cells (Gu, Y., A. F. Franco, Jr., P.D. Gardner, J. B. Lansman, J. R. Forsayeth, and Z. W. Hall. 1990. Neuron. 5:147-157). When incomplete combinations of AChR subunits were expressed, surface binding of 125I-alpha-bungarotoxin was not detected except in the case of alpha beta gamma which expressed less than 15% of that seen with all four subunits. Immunoprecipitation and sucrose gradient sedimentation experiments showed that in cells expressing pairs of subunits, alpha delta and alpha gamma heterodimers were formed, but alpha beta was not. When three subunits were expressed, alpha delta beta and alpha gamma beta complexes were formed. Variation of the ratios of the four subunit cDNAs used in the transfection mixture showed that surface AChR expression was decreased by high concentrations of delta or gamma cDNAs in a mutually competitive manner. High expression of delta or gamma subunits also each inhibited formation of a heterodimer with alpha and the other subunit. These results are consistent with a defined pathway for AChR assembly in which alpha delta and alpha gamma heterodimers are formed first, followed by association with the beta subunit and with each other to form the complete AChR. PMID- 1869589 TI - Identification and analysis of discrete functional domains in the pro region of pre-pro-transforming growth factor beta 1. AB - A series of site-specific insertion and deletion mutants was prepared in the pro domain of transforming growth factor beta 1 (TGF beta 1) encoded by simian TGF beta 1 cDNA. These mutants were transiently expressed in COS-1 cells and the ability of each to be properly processed, folded correctly, and secreted was determined by immunoblot analysis of cells and culture supernatants. Insertions in regions corresponding to amino acid residues 50, 154, and 170 blocked secretion; culture supernatants from COS-1 cells showed no immunologically reactive proteins, whereas intact cells contained high levels of the mutant polypeptides. Insertions in the middle portion of the pro domain at residues 81, 85, and 144 affected disulfide maturation of the mature TGF beta 1. An insertion at residue 110, on the other hand, appeared to destabilize the mature TGF beta 1 polypeptide, resulting in degraded growth factor. Relatively small (10 amino acids) to large (125 amino acids) deletion mutations in the pro domain of TGF beta 1, when expressed as the full-length pre-pro-TGF beta 1, appeared to block secretion. By contrast, if the pro domain (designated beta 1-latency-associated peptide [beta 1-LAP]) was expressed independently, deletion mutants in the region 40-110 were readily secreted by the COS-1 cells, whereas deletions in residues 110-210 either destabilized the structure of the protein or blocked its intracellular transport. Cross-linking assays employing radioiodinated TGF beta 1 and biological assays indicate that residues 50-85 of beta 1-LAP are required for association with mature TGF beta 1. PMID- 1869590 TI - Substratum-growth factor collaborations are required for the mitogenic activities of activin and FGF on embryonal carcinoma cells. AB - When P19 mouse embryonal carcinoma cells are grown in a serum-free N2 medium on surfaces of tissue culture plastic, they die within two days. The death of these P19 cells is prevented by activin A and basic FGF (bFGF). The cells do not divide under these conditions. However, when P19 cells are cultured on substrata of extracellular matrix proteins such as laminin and fibronectin, activin A and bFGF are potent mitogens. These data show that the substratum to which cells are exposed can regulate their mitogenic response to growth factors. PMID- 1869592 TI - Clinical research by pharmacists. PMID- 1869593 TI - Economics applied to the art of prescription pricing. PMID- 1869591 TI - Differential distribution and modulation of expression of alpha 1/beta 1 integrin on human endothelial cells. AB - In this paper we report that the integrin complex alpha 1/beta 1, a laminin/collagen receptor, is expressed on cultured foreskin microvascular endothelium, but is absent on endothelial cells from large vessels such as the aorta and umbilical and femoral veins. The restricted expression of integrin alpha 1/beta 1 to microvascular endothelium was also demonstrated in vivo, by immunohistochemical staining of human tissue sections. Alpha 1 specific antibodies reacted strongly with endothelial cells of small blood vessels and capillaries in several tissues, but not with endothelium of vein and arteries of umbilical cord. Expression of integrin alpha 1 can be induced in cultured umbilical vein endothelial cells by treatment with 5 ng/ml tumor necrosis factor alpha (TNF alpha). Induction of alpha 1 subunit expression also occurred after treatment of umbilical vein endothelium with 10(-5) M retinoic acid or with 10 nM PMA; Maximal induction of alpha 1 integrin was reached after 48 h of treatment and costimulation with TNF alpha and PMA resulted in a synergistic effect. The induction of alpha 1 integrin changed the adhesive properties of umbilical vein endothelial cells, by increasing the adhesiveness to collagen, laminin, and laminin fragment P1, while adhesion to fibronectin and laminin fragment E8 remained constant. The alpha 1 integrin is thus a marker of a specific population of endothelial cells and its expression confers distinctive properties of interaction with the underlying basal membrane. PMID- 1869594 TI - Pathophysiology of hypertension in diabetes mellitus--implications for management. AB - A variety of mechanisms may lead to the initiation and progression of hypertension in patients with diabetes mellitus; an understanding of their nature may provide a rational basis for the choice of management. Nevertheless, a decision on the management of an individual patient remains a matter of clinical skill and judgement. PMID- 1869595 TI - A comparison of the metabolic effects of flosequinan and propranolol in patients with non-insulin-dependent diabetes mellitus. AB - The effects of steady-state flosequinan, a new peripheral vasodilator, and propranolol on glucose tolerance and plasma lipids in 22 non-insulin-dependent diabetics were investigated in a randomized double-blind placebo-controlled, three-way crossover trial. Flosequinan produced no impairment of glucose tolerance compared with placebo. Propranolol produced significant increases in fasting plasma glucose (P less than 0.01) and increases in the area under the glucose tolerance curve (P less than 0.05) compared to placebo. No significant effects on cholesterol levels were seen on either treatment but triglyceride levels were significantly elevated on propranolol compared with placebo (P less than 0.01). These data suggest that flosequinan, used in therapeutic dosage, has no adverse metabolic effects on the non-insulin-dependent diabetic and this may be an advantage for a drug used in the treatment of hypertension or congestive heart failure. PMID- 1869596 TI - Pharmacokinetics of tobramycin in pregnant women. Safety and efficacy of a once daily dose regimen. AB - The pharmacokinetics of tobramycin, an aminoglycoside antibiotic, was investigated after a short intravenous infusion and once-daily dose regimen in two groups of nine pregnant women during the second (Group 1) and the third (Group 2) trimester of pregnancy. During these periods, the risk of infectious diseases is increased. Plasma concentrations of tobramycin were measured by fluorescence polarization immunoassay. The decrease in clearance (21%), at 28 weeks and more of gestation leads to an increase in half-life and the mean residence time (MRT) in the second group (33 and 29% respectively). The volume of distribution was unchanged in the two groups. No accumulation of the drug was observed in pregnant women. Pharmacokinetic disorders are correlated with the term and moreover with the weight deviation of women, i.e. the growth of the fetus. These findings suggest accumulation of the aminoglycoside antibiotic in the fetus. Moreover, the efficacy and the safety of this therapeutic regimen were excellent. To limit the potential nephrotoxicity and ototoxicity of tobramycin for the mother and the fetus, a once-daily dose regimen seems to be acceptable for the treatment of non-neutropenic pregnant women. PMID- 1869597 TI - An assessment of population-based and Bayesian methods to individualize digoxin doses shortly after the start of therapy for atrial fibrillation. AB - The accuracy of population-based methods and of Bayesian analysis to predict individual digoxin pharmacokinetic variables have been evaluated by their ability to predict a measured peak and trough serum digoxin concentration. We studied 13 digitalized patients (three women) whose mean (range) age and weight was 65.8 (60 78) years and 76.6 (68-101.6) kg and who had stable renal function. The population-based methods (using a clearance of 48.87 + 0.87 x creatinine clearance in ml/h/kg and volume of distribution, in litres, of either 7.3 x weight (kg) or 269 + 3.12 x creatinine clearance) were more than adequate for clinical purposes. The mean prediction errors of a measured steady-state peak concentration from these two population methods were -0.074 and 0.013 microgram/l respectively, whilst those of a measured trough concentration were -0.058 and 0.005 microgram/l. Bayesian analysis, using a sample drawn 11 h after the dose on day five of therapy, gave overall the least biased and most precise of the revised estimates. The mean prediction errors of peak and trough values using this sample were 0.069 and -0.005 microgram/l respectively. As expected, the closer the sample was drawn to the time of the trough concentration the more precise were the Bayesian-derived predictions. The value of the Bayesian technique to individualize digoxin doses could not be validated because it was not possible to distinguish between this and the population methods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869598 TI - Plasma concentrations of morphine in children with chronic pain--comparison of controlled release and regular morphine sulphate tablets. AB - Comparative plasma concentrations of morphine in two children with chronic pain who received controlled-release and regular morphine sulphate tablets are described. The controlled-release tablets were given every 12 h and regular tablets every 4 h. At steady-state, the maximum morphine plasma concentration (Cmax) was 24.1 ng/ml at 45 mg and 18.7 ng/ml at 30 mg of controlled-release morphine sulphate tablets. The Cmax was 17.6 ng/ml at 15 mg and 31.4 ng/ml at 20 mg dose of the regular tablets. The maximum concentration occurred at 2.0 and 2.5 h after controlled-release and 0.25 and 1.5 h after regular tablets. The minimum morphine plasma concentrations and the area under the plasma concentration-time curve normalized for dose were comparable for the controlled-release and regular tablets. These data indicate that controlled-release morphine sulphate may be well absorbed in relation to the regular tablets. If these results are confirmed in a large group of patients, the controlled-release morphine sulphate tablets may offer a convenient (less frequent) dosing compared with regular tablets in children suffering from chronic pain due to malignancy. PMID- 1869599 TI - A high-performance liquid chromatographic assay for phenylmercuric nitrate in the presence of zinc ions and its application to an assessment of the stability of phenylmercuric nitrate in zinc sulphate and zinc sulphate and adrenaline eye drops. AB - A high-performance liquid chromatographic assay for phenylmercuric nitrate in the presence of zinc ions has been developed. Application of the assay to zinc sulphate and zinc sulphate and adrenaline drops before and after autoclaving demonstrates that the phenylmercuric nitrate is chemically degraded in the zinc sulphate and adrenaline drops. PMID- 1869600 TI - Pharmacokinetics of intravenous midazolam during epidural anaesthesia. AB - Midazolam concentration curves versus time were analysed in 10 otherwise healthy patients (ASA I-II) with inferior limb pathologies. The benzodiazepine was used as an adjuvant agent to epidural anaesthesia in view of its lower residual effect compared with other intravenous benzodiazepines. Midazolam pharmacokinetics in these patients fitted an open two-compartment model. The plasma levels versus time corresponded to a biexponential process with a very rapid distribution phase (t1/2a = 5.7 +/- 2.4 min) and an elimination phase (t1/2 beta = 66 +/- 37 min). Mean values for distribution volumes in the central compartment and extrapolated values were Vc = 0.12 +/- 0.04 l/kg and V beta = 1.28 +/- 0.92 l/kg. This kinetic behaviour explains the rapid but short duration of midazolam action. The induction time, estimated from the start of hypnosis (eye closure), was from 60 to 120 s with i.v. injection. The duration of action for the dose administered was from 15 to 60 min, with plasma levels below 90 ng/ml upon eye opening. PMID- 1869601 TI - Evaluation of a communications skills workshop for hospital pharmacists. AB - The ability to communicate is an essential requirement for effective practice. Until recently, however, pharmacy students received no training in this area. The resultant inadequacy was carried forward into practice. Only now has the omission been recognized and attempts made to improve the situation among practising pharmacists. We designed an 8-h workshop on communication skills. It covered the basic principles of communication (Workbook A--preparatory work before the workshop) and their application (Workbook B + case studies, exercises and role playing--during the workshop). The workshop was presented to a group of hospital pharmacists in the Western Cape. At the end of the workshop participants completed a questionnaire on its usefulness, applicability and presentation on a five-point scale. Responses were counted, averaged and analysed by sex and age. Although the ratings were uniformly high (average 4.3 out of a possible 5.0) there were differences between men and women and between older and younger pharmacists. The possible reasons for and implications of these differences are discussed. PMID- 1869602 TI - One child, two homes, two cultures. PMID- 1869603 TI - Erectile dysfunction in diabetes. PMID- 1869605 TI - Acute bacterial bronchitis--nonexistent. PMID- 1869604 TI - Tubes. PMID- 1869606 TI - Chronic sinusitis--"a fresh look". PMID- 1869607 TI - Incorrect treatment held common. PMID- 1869608 TI - Extremely rapid ventricular rate in atrial fibrillation. PMID- 1869609 TI - Cocaine exposure in a newborn. PMID- 1869610 TI - Botulinum toxin A therapy in dystonia. AB - Local injections can decrease posturing and pain in 70% to 90% of patients for up to eight months. Responses can be extended with further injections. PMID- 1869611 TI - Mitral valve surgery: replacement vs reconstruction. AB - In comparative series, valve repair has been effective, with few of the problems- notably, thromboemboli--associated with replacement procedures. Although many patients are elderly and have coronary artery disease, reparative surgery not only is low-risk but also allows earlier intervention, before irreversible left ventricular damage occurs. PMID- 1869612 TI - Energetics and the failing heart. AB - The likelihood of an imbalance between energy production and energy utilization in the failing heart has important implications for patient management. Vasodilators and negative inotropic agents might prolong survival by improving the balance. One vasodilator class--angiotensin converting enzyme inhibitors--has had a remarkable effect on prognosis. PMID- 1869613 TI - The long pause. The discovery and rediscovery of penicillin. PMID- 1869614 TI - An automated method for the determination of diclofenac sodium in human plasma. AB - An automated method utilizing laboratory robotics has been developed for quantifying diclofenac sodium concentrations in human plasma. The robotic system aliquots the biological sample, adds the internal standard (CGP 4287), extracts the compounds from the acidified biological matrix (pH less than 2) into an organic phase (hexane-isopropyl alcohol), and concentrates the extracts for reversed-phase, high-performance liquid chromatographic (HPLC) analysis. The laboratory robot is directly interfaced to the HPLC system, and the data are automatically collected and results calculated. Separation is achieved on a 3 microns ODS (6.2-mm x 8.0-cm) column with ultraviolet (UV) detection of the drug and internal standard at 280 nm. Recovery and reproducibility assessments indicate good accuracy (overall mean relative recovery of 99.8%) and precision (coefficient of variation from 0.5 to 11.1%) over the diclofenac sodium concentration range of 5.0-1000 ng/mL, with a quantification limit of 5.0 ng/mL. The method has been successfully applied to a pharmacokinetic study in which normal volunteers received 150 mg of a prototype controlled-release formulation of diclofenac sodium. PMID- 1869615 TI - Changes in cytosolic calcium, bleb formation, and cell death in neural crest cells treated with isotretinoin and 4-oxo-isotretinoin. AB - Information regarding the cytopathologic mechanism of action of the retinoids [isotretinoin (IR) and 4-oxo-isotretinoin (4-OIR)] on neural crest cells (NCCs) in culture was sought. Those pathophysiologic alterations in cell metabolism studied were: cell blebbing (xieosis), free radical formation, cell viability, and cellular calcium homeostasis. Cells were treated with IR or 4-OIR in the presence of high (1.4 mM) and low (5.0 microM) levels of extracellular calcium ions. Recently developed techniques utilizing fluorescent molecular probes for calcium analyses, i.e., Fura 2AM, were used to study the effects of these drugs on the cytosolic calcium concentration of NCCs. The effects of IR and 4-OIR on NCC viability, [Ca++]int, were contrasted with the effects of certain sulfhydryl drugs (HgCl2, NEM, PCMBS) and calcium ionophores (ionomycin, A23187), agents known to perturb cell membranes, increase cytosolic calcium loads, and induce cell injury and subsequent cell death. Both retinoids were shown to induce an increase in the generation of superoxide radicals (SO) and increase the influx of calcium ions by the NCCs, thus increasing [Ca++]int by several hundred percent within 5 to 10 min. The liberation of SO was calcium dependent. These early effects were accompanied by an increase in cell blebbing activity. Also, a significant decrease in NCC viability was seen as early as 10 min after the addition of IR or 4-OIR to the incubation medium. 4-OIR proved to be the more potent of the two retinoids tested. The severity of these effects on NCC metabolism was dependent on medium calcium concentration with all changes being increased in the presence of the higher extracellular calcium levels. From the data presented it appears as though the retinoids cause a rapid elevation in cytosolic [Ca++]int possibly by purturbing the integrity of the cell membrane, denaturing membrane Ca-ATPase activity, or both. Retinoid-induced changes in membrane activity are evidenced by increased surface blebbing and superoxide formation. The prolonged elevation of intracellular [Ca++] may be directly related to depressed NCC viability and thus explain the known teratogenic effects of these drugs and their relationship to ectomesenchymal cell hypoplasia and craniofacial dysmorphogenesis. PMID- 1869616 TI - Picasso and the art of distortion and dislocation: the artist as researcher and experimentalist. AB - This paper is divided into four parts. In the first part, some general ideas about Picasso are set forth including: his association with multiple artistic innovations; his use of many different media; his notions of beauty and the relationship between art and nature; his ideas about the placement of body parts, symmetry, and color; and his relish in producing paintings with shock value. Emphasis is placed on the relationship between art and science and on Picasso's role as a researcher and experimentalist. In the second part, works of art during the cubist and postcubist years are discussed with emphasis on the development of simultaneity--the coexistence of different views of an object in the same picture. Topics included are: facial grafting; facial accommodation; multifacialism; profile insertion; snout formation, elevation, and rotation; concurrent faces; and more comprehensive simultaneity. In the third part, other influences on Picasso are presented including: the effects of action, motion, and activity; Surrealism and sexual symbolism; and Picasso's artistic treatment of women. In the fourth part, a comparison is made between Picasso's experiments and nature's experiments. PMID- 1869617 TI - Inner enamel epithelia synthesize and secrete enamel proteins during mouse molar occlusal "enamel-free area" development. AB - Mesenchyme-derived instructions for odontogenic epithelial differentiation into ameloblasts and the production of enamel matrix has been well established. However, it is not known how position-specific differences within the enamel organ of rodent molar tooth organs regulate the enamel-forming vs. the enamel free areas in the developing cusp. Light microscopy, transmission electron microscopy, and immunocytochemistry using a rabbit anti-mouse amelogenin antibody, were used to map the position-specific patterns within the enamel organ. In the enamel-forming area, ameloblasts were associated with stratum intermedium. In the enamel-free area, another cell type was interposed between inner enamel epithelia (IEE) and stratum intermedium. IEE in the enamel-free area did not have Tomes' processes and secreted enamel matrix not only toward dentin but also between IEE cells. IEE became confluent with stellate reticulum; at this position stratum intermedium cells were no longer detected. The thickness and orientation of dentin matrix collagen fibers in the enamel-free area were different from the fibers in the enamel-forming area. These results suggest that the patterns of epithelial cell-cell and cell-matrix associations during position specific enamel organ epithelial differentiation may regulate ameloblast matrix synthesis and/or the matrix secretion pathway. PMID- 1869618 TI - Temperament and family characteristics as predictors of children's reactions to hospitalization. AB - Findings from a study of 47 children 4 to 12 years old who received tonsillectomies at a children's hospital indicated that adjustment before hospitalization was the strongest predictor of postsurgical adjustment. However, certain temperamental and mother-child relationship factors also were strongly related to and predictive of posthospitalization outcomes. Children who displayed the most positive reactions were temperamentally more rhythmical (i.e., had regular, predictable behavior), more approaching to new experiences and people, more adaptable to change and positive in mood, and more responsive. Although family adaptability and cohesion were not significantly associated with children's reactions to hospitalization, maternal trait anxiety and maternal overprotection, rejection, and overindulgence of the child were correlated with poorer adjustment. The findings have practical implications to helping children adjust more effectively to surgery and hospitalization, and they contribute to our understanding of resiliency and vulnerability in children. PMID- 1869619 TI - Physicians' prognoses about the quality of life for infants with intraventricular hemorrhage. AB - There is an absence of definitive information concerning the long-term outcome of children born with intraventricular hemorrhage (IVH). Physicians, however, are called on to prognosticate about the future quality of life of these children. Our study examined pediatricians' and neonatologists' prognoses for infants with grade I- and grade-IV IVH and the impact of those prognoses on recommendations for treatment. A national random survey of 289 pediatricians and 283 neonatologists found that both groups expected infants with grade-I IVH to have slight impairments to future development, whereas infants with grade-IV IVH were expected to have severe impairments. Physicians prognosticated that infants with grade-IV IVH would function at a moderate to severe level of mental retardation, incapable of any employment, and residing in an institution. Furthermore, physicians would encourage parents to seek medical treatment of respiratory distress for the infant with grade-I IVH but were neutral or would discourage parents from seeking treatment for the infant with grade-IV IVH. Lastly, physicians' prognoses were significantly related to their recommendations for treatment. Several differences in physicians' prognoses and recommendations were found to be related to their discipline and training. PMID- 1869620 TI - Apparent life-threatening events during infancy: a follow-up study of subsequent growth and development. AB - This research was an exploratory follow-up study of 51 infants who had experienced an "apparent life-threatening event" (ALTE) characterized by apnea and subsequent home cardiorespiratory monitoring. The purpose was to (1) describe relationships among perinatal characteristics, birth status, recurrent apnea, and ratings of the home environment, and (2) relate these measures to infant growth and developmental outcomes. The method included home visits and assessments of infant outcomes at 10 to 14 months, followed by retrospective review of obstetric and infant medical records. Perinatal characteristics, birth status, and recurrent apnea were interrelated correlates of both growth and developmental outcomes. The ratings of the home environment (HOME [Home Observation for Measurement of the Environment] Scale) were related to developmental outcomes and to a lesser extent to physical growth status. Hierarchical regression analysis entering gestational age, obstetric and postnatal complications, apnea, and HOME subscale 4 (provision of appropriate play materials) significantly enhanced the predictability of mental and psychomotor development. Future longitudinal research is necessary to explore whether the association between apnea and specific infant outcomes attenuates over time and whether the relationship is direct or mediated by parental perception of infant vulnerability and altered caregiving style. PMID- 1869622 TI - Prevalence of behavioral symptoms and the relationship of child, parent, and family variables in 4- and 5-year-olds: results from the Ontario Child Health Study. AB - This study presents the frequency of behavioral symptoms in 4- and 5-year-old children as reported by parents in the Ontario Child Health Study. It also examines the relationship of the presence of child, parent, and family variables with parent-reported total scale scores. Eight of the 135 items were reported to be present by the parents of 50% or more of the 437 children in the sample. For 18 items, the prevalence rates for boys were significantly higher than for girls. Multiple regression analysis resulted in slightly different child, parent, and family variables influencing scores when total scores and scores on severe items only were used as dependent variables. Two variables appeared in both models: general health of the child and family status. Some of the child, parent, and family variables found to be associated with behavior disorder in older children do not appear to have as strong an association with disorder in 4- and 5-year olds. PMID- 1869621 TI - Blood pressure reactivity to exercise: stability, determinants, family aggregation, and prediction. AB - Previous studies have shown blood pressure reactivity to exercise predicts future resting blood pressure. Subjects in this study were 206 healthy Mexican-American and Anglo-American families with fifth or sixth grade children. A total of 539 children (mean age = 12 years) and parents (mean age = 37 years) had complete data at baseline, and 79% were remeasured 48 months later. Blood pressure was measured during a submaximal cycle ergometer fitness test. Reactivity measures included systolic blood pressure at 70% of maximal heart rate (SBP70) and slope of the blood pressure-heart rate association during exercise (SLOPE). Stability of reactivity measures over 24 months varied from .22 to .63 (all p less than 0.001). Correlates of blood pressure reactivity in parents included resting heart rate, gender, age, and sodium intake. Correlates of reactivity in children included resting heart rate, body mass index, and age. Modest but significant levels of family aggregation of blood pressure reactivity were observed. In stepwise multiple regression analyses, SBP70 at baseline predicted resting blood pressure 48 months later in parents but not in children. The present results confirm previous studies indicating systolic blood pressure reactivity to exercise is a significant predictor of later resting blood pressure. PMID- 1869623 TI - The development of scales to measure knowledge and preference for diet and physical activity behavior in 4- to 8-year-old children. AB - Although there is a sizable literature on determinants of health-related habits in adults, relatively little attention has been paid to influences on health habits in children. The purpose of this study was to (a) develop practical, reliable, and valid measures of knowledge of and preference for cardiovascular disease-related diet and exercise behaviors in children, and (b) assess parental influences on children's knowledge and preference. Eighty-one 4- to 8-year-old children from diverse ethnic backgrounds and their parent or legal guardian participated. Children were presented with 15 attractive photo-pairs of foods. One photograph was of a "healthful" food or activity, and the other was "unhealthful." They were asked to identify which food/activity of the pair they preferred, and which one they thought was more healthy. Children were retested after 1 week to determine test-retest reliability. Validity of the preference tests was determined by giving the child actual choices of the same activity and food pairs. Validity of knowledge tests was determined by testing children after an educational intervention session. The alpha coefficients, test-retest reliabilities, and validity data generally indicated that food preference and knowledge tests had adequate psychometric properties, but the physical activity scales did not. Very few parental influences on health-related behavior were detected. PMID- 1869624 TI - Bulimia nervosa in adolescence. AB - Investigations of bulimia nervosa have focused primarily on adult samples, although bulimia nervosa commonly has its onset in adolescence. Pediatricians are often questioned about its etiology, course, and treatment. In an attempt to provide pediatricians with answers, we integrate findings from recent epidemiological and treatment studies with a clinical report of 18 women who developed bulimia nervosa during their teens and sought treatment at our eating disorders clinic. PMID- 1869625 TI - Who cares for the young adult with mental retardation? PMID- 1869626 TI - Educare: new product, new future. AB - On September 2, 1990, something very informative about the evolution of early childhood programs in the minds of people appeared in The New York Times. Perhaps only another historian of trivia would have noticed it, but it was significant. The Sunday crossword puzzle had the following cue for 4 down: "Places for day care" (spelled, with the purist's uncertainty, with a hyphen). Even such a cautious horizontal-vertical weaver as I am did not have to wait very long before filling in the correct 10 letters: "preschools." Preschools = day-cares; day cares = preschools. I am told that actors and authors and scientists know that they have it made when their names are required as solutions in a Times crossword puzzle. If so, perhaps we now have tangible proof that those of us have at last been heard who have urged acceptance of the concept that early childhood education (or preschool education) and child care (or day care) are really one and the same essential service operated for different lengths of time. Day care, the illegitimate child of the scientific field that gave birth to the early childhood movement, has turned out to be the only offspring sufficiently well endowed and robust to make it in the modern world. It is the only one possessing the characteristics that will enable it to take the family enterprise into the future. At this juncture, near the close of the century during which programs for young children multiplied to the point where they cannot be ignored as significant factors in family and public life, we are on the threshold of a new era.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869627 TI - Anxiety among hospitalized latency-age children. PMID- 1869628 TI - Issues and traits that influence dentists' professional satisfaction and economic success. PMID- 1869629 TI - The AIDS "epidemic" is ending and dentists have never really been at risk. PMID- 1869630 TI - Growth cones and axon trajectories of a sensory pathway in the amphibian spinal cord. AB - Central axons of sensory ganglion (SG) neurons of the Xenopus tail enter the spinal cord via the ventral roots and travel dorsally and rostrally following a diagonal course within the lateral marginal zone (LMZ) to reach the dorsolateral fasciculus (DLF) (Nordlander et al.: Brain Res., 440:391-395, 1988). Axons are dispersed as they cross the cord. At the DLF they turn and travel together rostrally, sharing the fascicle with axons of primary sensory neurons (Rohon Beard cells) already present in the tract. In this paper we analyze the growth patterns of the central projections of SG axons in the tail by using HRP applied to proximal branches of tail spinal nerves. Growth cones of the diagonal route are variable in configuration, often bearing processes that spread within the LMZ. Once the DLF, growth cones change shape, becoming distinctly linear. While growth cones navigating the diagonal part of the route never contact or fasciculate with other diagonal SG axons, SG growth cones and axons of the DLF are more closely associated with their fellows. Measurements of the slopes of SG axons in the diagonal route indicated a limited range with a mean of 23 degrees with respect to the cord axis. On the basis of these observations, we conclude that 1) navigational patterns for growth cones of this pathway differ for the diagonal versus the DLF part of its course, and 2) fasciculation is not a mechanism used by SG axons to reach the DLF, but that instead, each axon is able to find its way independently. PMID- 1869631 TI - Connectivity of glycine immunoreactive amacrine cells in the cat retina. AB - The synaptic relationships of glycine immunoreactive amacrine cells in the cat retina were studied through the use of postembedding immunogold techniques. Glycine immunoreactive amacrine cells were found to synapse extensively with other amacrines and ganglion cells, particularly in strata 1-3 of the inner plexiform layer. This contrasts with GABA immunoreactive amacrine cells which provide major input to bipolar cells in strata 3-5. Glycine containing amacrine terminals exhibited diversity with respect to the morphology of their synaptic vesicles. The three types of terminals which could be distinguished were characterized by small pleomorphic (32-35 nm), medium-sized flattened (38-45 nm), or larger rounded (48-55 nm) vesicles. Comparison of retinal sections processed for glycine immunoreactivity with adjacent sections stained for GABA reactivity revealed a colocalization of glycine and GABA in 3% of the cells in the amacrine layer and approximately 40% of the cells in the ganglion cell layer. The amacrine terminals in which glycine and GABA were colocalized typically contained the small pleomorphic type of vesicles. PMID- 1869632 TI - Primate supplementary eye field. II. Comparative aspects of connections with the thalamus, corpus striatum, and related forebrain nuclei. AB - The supplementary eye field (SEF) was defined electrophysiologically in behaving monkeys to study its connections with the diencephalon and corpus striatum. The specificity of SEF pathways was determined with horseradish peroxidase (HRP) histochemistry to compare its connections with those of the arcuate frontal eye field (FEF), contiguous dorsocaudal area 6 (6DC), and primary motor cortex (M1, arm/hand region). Results indicate that patterns of SEF connectivity were similar to the FEF and markedly different from areas 6DC and M1. Primary reciprocal thalamic pathways of the SEF were with the magnocellular ventral anterior (VA) nucleus, medial parvicellular VA, medial area X, and paralaminar medialis dorsalis (multiformis and parvicellularis). FEF showed similar connections but its most robust pathway was with MD rather than VA. In contrast, area 6DC showed the most extensive reciprocal connections with lateral VApc and lateral area X with only sparse connections with paralaminar MD. Area 6DC also exhibited reciprocal connections with the ventral lateral (VL) complex and the ventral posterior lateral nucleus, pars oralis (VPLo). M1 showed dense bidirectional connections with VPLo, and to a lesser extent, with VL. M1 pathways with the medial dorsal nucleus were negligible. All areas exhibited connections with the paracentral and central lateral nuclei and only M1 lacked connections with the central superior lateral nucleus. SEF and FEF exhibited similar efferent projections to the caudate and putamen. In the caudate, terminal fields were restricted to a central longitudinal core while those from area 6DC were more widely distributed. Eye field efferents were restricted to the putamen's face region while 6DC projections were more exuberant. The arm/hand region of M1 projected to the arm/hand region of the putamen. Pathways are discussed with respect to their significance in oculomotor control. PMID- 1869633 TI - GABA-immunoreactive neurons in the nematode Ascaris. AB - gamma-Aminobutyric acid (GABA) immunoreactive neurons in the cephalic, somatic, and caudal regions of the Ascaris nervous system were visualized with serial section and whole-mount GABA immunocytochemistry. In the ventral and dorsal nerve cords, GABA-like immunoreactivity (GLIR) is localized to the neurites and cell bodies of identified inhibitory motor neurons and to two fibers, one in each cord, that arise from neurons in the nerve ring. GLIR is absent from identified excitatory motor neurons and from ventral cord interneurons. In neurons containing GLIR, immunoreactivity was present throughout the cell, which argues against an exclusive localization of GABA at conventional synapses. In whole mounts, ten GABA-immunoreactive neurons were present in the cephalic region. These include four nerve ring-associated cells (the RME-like cells), two bilaterally symmetrical pairs of lateral ganglia neurons (the amphid-GABA and deirid-GABA cells) and one bilaterally symmetrical pair of ventral ganglion cells (the VG-GABA cells). In sections, the RME-like cells and the VG-GABA cells were consistently stained through the cephalic region. However, anti-GABA staining of the lateral ganglia cells in sections was light, thus suggesting that they contain less GLIR than the other more intensely stained GABA-immunoreactive neurons. In the caudal region, a single GABA-immunoreactive neuron was present in the dorsal rectal ganglion. Our data suggest that these ten cephalic neurons, and a single dorsal rectal ganglion neuron, use GABA as a neurotransmitter. PMID- 1869634 TI - Distribution of 3H-GABA uptake sites in the nematode Ascaris. AB - The distribution of uptake sites for the inhibitory neurotransmitter gamma aminobutyric acid (GABA) in the nematode Ascaris suum was examined by autoradiography of 3H-GABA uptake. Single neural processes in both the ventral and dorsal nerve cords were labeled with 3H-GABA. Serial section analysis identified the cells of origin of these processes as the RMEV-like and RMED-like neurons. These cells belong to a set of four neurons in the nerve ring, all of which are labeled by 3H-GABA. 3H-GABA labeling of at least two other sets of cephalic neurons was seen. One of these pairs consists of medium-sized lateral ganglia neurons, located at the level of the amphid commissure bundle. A second pair is located in the lateral ganglia at the level of the deirid commissure bundle. The position and size of these lateral ganglia cells suggest that they are the GABA-immunoreactive lateral ganglia cells frequently seen in whole-mount immunocytochemical preparations (Guastella et al., J Comp Neurol 307:584-597, 1991). Four neuronal cell bodies located in the retrovesicular ganglion were also labeled with 3H-GABA. These cells, which are probably cholinergic excitatory motor neurons, do not contain detectable GABA-like immunoreactivity. Heavy labeling of muscle cells was also observed. The ventral and dorsal nerve cord inhibitory motor neurons, which are known to contain GABA-like immunoreactivity, were not labeled above background with 3H-GABA. Together with the experiments reported previously (Guastella et al., J Comp Neurol 307:584-597, 1991), these results define three classes of GABA-associated neurons in Ascaris: 1) neurons that contain endogenous GABA and possess a GABA uptake system; 2) neurons that contain endogenous GABA, but that either lack a GABA uptake system or possess a GABA uptake system of low activity; 3) neurons that possess a GABA uptake system, but that lack endogenous GABA. PMID- 1869635 TI - Histamine-immunoreactive neurons in the midbrain and suboesophageal ganglion of sphinx moth Manduca sexta. AB - This paper describes the distribution of histamine-like immunoreactivity in the midbrain and suboesophageal ganglion of the sphinx moth Manduca sexta. Intense immunocytochemical staining was detected in ten bilateral pairs of neurons in the median protocerebrum and in one pair of neurons in the suboesophageal ganglion. Whereas most areas of the brain and suboesophageal ganglion are innervated by one or more of these neurons, typically no immunoreactive fibers were found in the mushroom bodies, the protocerebral bridge, and the lateral horn of the protocerebrum. The 11 histamine-immunoreactive neurons were reconstructed from serial sections. Ten neurons have bilateral arborizations, often with axonal projections in symmetric areas of both hemispheres. One neuron, whose soma resides in the lateral protocerebrum, has only unilateral projections. Of the 11 neurons, 6 occur in pairs with similar morphological features. In addition to these neurons, weak histamine-like immunoreactivity was detected in 7-13 interneurons that were not reconstructed individually. The central projections of the ocellar nerves from the intracranial ocelli also exhibit histamine-like immunoreactivity. The single-cell reconstructions reveal similarities between the organization of histamine- and serotonin-immunoreactive neurons in the brain and suboesophageal ganglion of this insect. PMID- 1869636 TI - Immunocytochemical localization of octopamine in the central nervous system of Limulus polyphemus: a light and electron microscopic study. AB - We have determined the distribution and localization of the monoamine octopamine in the prosomal central nervous system of the horseshoe crab, Limulus polyphemus, by light and electron microscopic immunocytochemistry. Sixteen discrete clusters of octopamine-like immunoreactive neurons are situated bilaterally in the tritocerebrum and circumesophageal ring of fused thoracic ganglia. Two pairs of anterior clusters are located laterally in the cheliceral and first pedal ganglia; the remaining six pairs of clusters are located ventromedially in the second through fifth pedal ganglia, chilarial ganglia, and opercular ganglia. The immunoreactive somata range from about 40 to 100 microns in diameter and occur in clusters of 12-24 cells. There is extensive distribution of octopamine immunoreactive nerve fibers in Limulus; dense fiber tracts course anteroposteriorly through the central nervous system, and most neuropil regions are innervated by immunoreactive processes and terminals. This wide distribution of octopamine-like immunoreactivity provides an anatomical basis for the several effects of octopamine in Limulus. We determined the subcellular localization of octopamine by postembedding immunoelectron microscopy. The immunogold-labelled terminals are morphologically unique; they contain large, distinctively shaped dense-core granules, typically cylindrical with a prominent indentation in one end. These large granules are 100-150 nm in diameter and range from 150-400 nm in length. The dense labelling of these unusual granules with immunogold particles indicates that octopamine is sequestered in or associated with the granules. PMID- 1869637 TI - Intracerebral grafting of cultured autologous skin fibroblasts into the rat striatum: an assessment of graft size and ultrastructure. AB - To identify a suitable donor cell population for gene therapy applications to the central nervous system, primary fibroblasts isolated from skin biopsies and maintained in culture are employed as autologous cells for intracerebral grafting within the adult rat striatum. Results from the present investigation reveal that cultured primary skin fibroblasts cease to proliferate once they reach confluence; these cells are thus contact inhibited in vitro. Following implantation within the striatum, the volume of the primary fibroblast grafts, stained immunohistochemically for fibronectin, does not differ significantly at 3 and 8 weeks. The graft size is dependent on the density of the cell suspension, but not dependent on either the number of passages the cells are taken through in culture prior to grafting or on the postoperative survival period. Ultrastructural evidence reveals that at 8 weeks the grafts are composed primarily of collagen and fibroblasts with rough endoplasmic reticulum and vesicles. Reactive astrocytic processes and phagocytic cells are also present in the grafts. The grafts are extensively vascularized with capillaries composed of nonfenestrated endothelium; intercellular junctions are evident at sites of apposition between endothelial cells. It is concluded that primary skin fibroblasts are able to survive for at least 8 weeks following intracerebral implantation and continue to synthesize collagen and fibronectin in vivo. Also, the grafts maintain a constant volume between 3 and 8 weeks, thereby indicating that primary skin fibroblasts do not produce tumors. Finally, dynamic host-to graft interactions--including phagocytic migration, astrocytic hypertrophy and infiltration within the grafts, and angiogenesis--are features that constitute the structural integration of primary skin fibroblasts grafted within the adult rat central nervous system. PMID- 1869638 TI - Tumor necrosis factor. AB - Tumor necrosis factor is important in systemic and cutaneous defense, homeostasis, and many disease states. The numerous and diverse effects of tumor necrosis factor are best understood when considered as concentration-dependent, with normal homeostasis progressing to defense followed by toxic effects. Understanding tumor necrosis factor is important for the dermatologist as more studies appear in our literature and potential clinical uses of tumor necrosis factor (and possible anti-tumor necrosis factor agents) are realized. PMID- 1869639 TI - Papular dermatitis in adults: subacute prurigo, American style? AB - Determining the best treatment for recurrent pruritic papular eruptions that do not fit well into a diagnosis (of either atopy or some other diagnosis) is sometimes frustrating. We have studied 12 patients with recurrent pruritic papular eruptions by obtaining extensive histories and by performing skin biopsies, immunofluorescence studies, and screening patch tests. The eruptions in this group are not atopic by strict criteria but have atopic features and are without a determinable exogenous cause. Histologic features resemble papular urticaria, but there is no history to suggest arthropod bites. Patients with this type of eruption have features similar to those with subacute prurigo, and they respond to variable combinations of topical or systemic corticosteroids, systemic antihistamines, and UVB or UVA. We suggest that the designation of subacute prurigo might be more appropriate for patients with these findings. PMID- 1869640 TI - Pityriasis rubra pilaris and HIV infection. AB - Many cutaneous diseases have been reported in patients with human immunodeficiency virus infection. We report two patients with pityriasis rubra pilaris and human immunodeficiency virus infection. In one patient, the onset of pityriasis rubra pilaris preceded the discovery of human immunodeficiency virus infection. In the second patient, the onset of pityriasis rubra pilaris occurred shortly after the patient tested positive for human immunodeficiency virus infection. Both patients had a severe form of pityriasis rubra pilaris, and both had a minimal therapeutic response to etretinate. PMID- 1869641 TI - Childhood epidermolysis bullosa acquisita. Report of three cases and review of literature. AB - Epidermolysis bullosa acquisita is an acquired subepidermal blistering disease with variable clinical, pathologic, and immunologic features. The disease has been reported infrequently in adults and only rarely in children. We describe three new cases of childhood epidermolysis bullosa acquisita, review three previously reported cases, and contrast the features of the disease in children with those in adults. The results suggest that both children and adults with epidermolysis bullosa acquisita have variable clinical and pathologic features that may mimic other bullous diseases. Epidermolysis bullosa acquisita is characterized by a chronic course, poor response to therapy, and occasional clinical remissions. PMID- 1869642 TI - Metastatic basal cell carcinoma: report of twelve cases with a review of the literature. AB - Metastatic basal cell carcinoma was found in 12 patients at the University of Wisconsin Mohs Surgery Clinic during the period 1936 to 1989. All patients were white men. The time of onset of the primary tumor ranged from childhood to 71 years. Eleven patients had previous treatment for basal cell carcinoma; two patients had received x-ray radiation to the face for teenage acne. The locations of the primary basal cell carcinomas were the face (n = 10), back (n = 1), and arm (n = 1). The primary tumors ranged from 3.6 x 3.0 to 20.0 x 7.0 cm. The interval from onset to the first sign of metastases ranged from 7 to 34 years. In all cases, the primary tumor was histologically identical to the metastatic lesion. Perineural extension of the basal cell carcinoma in the primary lesion was found in five cases. Regional lymph nodes were the most frequent site of metastasis. Treatment consisted of a combination of surgery, radiation, and chemotherapy. Only two patients survived more than 5 years after surgical treatment. One patient has survived 25 years and is still alive. PMID- 1869644 TI - Intralesional interferon alfa-2b in the treatment of basal cell carcinoma. Immunohistochemical study on cellular immune reaction leading to tumor regression. AB - Four patients with basal cell carcinomas were treated with intralesional injections of interferon alfa-2b (1.5 million IU per injection) three times a week for 2 weeks. Histopathologic examination of biopsy specimens of the lesions confirmed the absence of basal cell carcinoma in all cases 4 weeks after completion of therapy. A dense mononuclear cell infiltrate and numerous ectatic blood vessels were present in the dermis at the sites of previous basal cell carcinoma. Immunohistologic analysis of the dermal infiltrate revealed a marked increase of Leu-4+ T cells with a slight predominance of Leu-3+ helper/inducer T cells over Leu-2+ suppressor/cytotoxic T cells. Most of the dermal infiltrate expressed HLA-DR antigen. In addition, Leu-11+ natural killer cells were observed in the dermal infiltrate. Immunohistologic changes in the skin lesions at the sites of previous basal cell carcinoma suggest that intralesional interferon alfa 2b acts on tumor cells by enhancement of local T-cell-mediated immune responses. PMID- 1869643 TI - Controlled release of benzoyl peroxide from a porous microsphere polymeric system can reduce topical irritancy. AB - Skin absorption of benzoyl peroxide from a topical lotion containing freely dispersed drug was compared with that from the same lotion in which the drug was entrapped in a controlled-release styrene-divinylbenzene polymer system. In an in vitro diffusion system, statistically significant (p = 0.01) differences were found in the content of benzoyl peroxide in excised human skin and in percutaneous absorption. In vivo, significantly (p = 0.002) less benzoyl peroxide was absorbed through rhesus monkey skin from the polymeric system. This controlled release of benzoyl peroxide to skin can alter the dose relation that exists between efficacy and skin irritation. Corresponding studies showed reduced skin irritation in cumulative irritancy studies in rabbits and human beings, whereas in vivo human antimicrobial efficacy studies showed that application of the formulations containing entrapped benzoyl peroxide significantly reduced counts of Propionibacterium acnes (p less than 0.001) and aerobic bacteria (p less than 0.001) and the free fatty acid/triglyceride ratio in skin lipids. These findings support the hypothesis that, at least for this drug, controlled topical delivery can enhance safety without sacrificing efficacy. PMID- 1869645 TI - Response to tumor necrosis factor in two cases of psoriasis. AB - A 70-year-old woman was treated for renal cell carcinoma with recombinant human tumor necrosis factor, 450,000 U/m2 of body surface area, daily for 5 days, once a month. She had had psoriasis for 25 years. After two courses of recombinant human tumor necrosis factor her psoriasis resolved. A 40-year-old man with severe psoriasis was subsequently treated with a total of seven complete and incomplete 5-day courses of recombinant human tumor necrosis factor at doses of 50,000 to 300,000 U/m2/day. Significant toxicity (fever, chills, hypertension, and hypotension) was encountered. Partial resolution of the lesions was seen. Tumor necrosis factor is an active agent in psoriasis. PMID- 1869646 TI - A double-blind, vehicle-controlled study evaluating masoprocol cream in the treatment of actinic keratoses on the head and neck. AB - This double-blind, vehicle-controlled, multicenter study evaluated the efficacy and safety of a new topical antineoplastic agent, masoprocol, in the treatment of actinic keratoses of the head and neck. Of the 113 patients who applied topical masoprocol twice a day for 14 to 28 days, there was a mean decrease in actinic keratoses from 15.0 to 5.4 and a median percent reduction from baseline actinic keratosis count of 71.4% at the 1-month follow-up visit. Comparable numbers for the vehicle-treated group were 13.4 to 11.1 actinic keratoses and 4.3% median percent reduction. Irritation, as manifested by erythema or flaking, occurred in 61.5% of topical masoprocol-treated patients versus 26.7% of those treated with vehicle and did not correlate with clinical response. Topical masoprocol appears to be useful in the treatment of actinic keratoses. PMID- 1869647 TI - Topical photoprotection for hereditary polymorphic light eruption of American Indians. AB - We evaluated the photoprotective efficacy of a broad-spectrum sunscreen containing a UVA screen (butyl methoxydibenzoylmethane) and a UVB screen (octyl dimethyl p-aminobenzoic acid) in patients with hereditary polymorphic light eruption. At least 18 of the 30 patients who enrolled in the study were sensitive to sunlight through window glass, an indication of UVA sensitivity. Of the 21 patients who completed the clinical trial, the physician's evaluation was that 18 (86%) obtained good to excellent results. Self-evaluation by the patients revealed that 16 (76%) noted more photoprotection than from previous treatments. PMID- 1869648 TI - Neurocutaneous melanosis: definition and review of the literature. AB - Neurocutaneous melanosis is a rare congenital syndrome characterized by the presence of large or multiple congenital melanocytic nevi and benign or malignant pigment cell tumors of the leptomeninges. The syndrome is thought to represent an error in the morphogenesis of the embryonal neuroectoderm. We review 39 reported cases of neurocutaneous melanosis and propose revised criteria for diagnosis. Most patients with neurocutaneous melanosis presented in the first 2 years of life with neurologic manifestations of increased intracranial pressure, mass lesions, or spinal cord compression. Leptomeningeal melanoma was present in 62% of the cases, but even in the absence of melanoma, symptomatic neurocutaneous melanosis had an extremely poor prognosis. Useful diagnostic procedures include cerebrospinal fluid cytology and magnetic resonance imaging with gadolinium contrast. Patients may be aided by palliative measures such as shunt placement to reduce intracranial pressure. Dermatologists in their follow-up of patients with large or multiple congenital melanocytic nevi should be aware of this condition, to aid in prompt diagnosis and because the treatment of cutaneous lesions may be altered in the presence of symptomatic neurocutaneous melanosis. PMID- 1869649 TI - Percutaneous injury during dermatologic surgery. AB - An anonymous survey was conducted among 100 randomly selected fellows of the American Society for Dermatologic Surgery. Forty-one respondents provided information about their experience with percutaneous injury. Causes of injury during 6278 invasive procedures performed during a 1-month period included suture needlesticks (two injuries), injection needlestick (one), needle recapping (one), scalpel blade (one), skin hook (one), and an injury during the transport of an instrument (one). Dermatologic surgeons were more likely to injure their dominant fingers. Attitudes of dermatologic surgeons were surveyed regarding operating on patients while the physician or assistant was actively infected with human immunodeficiency virus, hepatitis B virus, herpetic whitlow, or paronychia caused by Staphylococcus aureus. Dermatologic surgeons believed that they should be allowed to operate while infected with human immunodeficiency virus (41.5%), hepatitis B virus (40%), herpetic whitlow (25%), and paronychia caused by S. aureus (20%). Few dermatologic surgeons would disclose preoperatively to patients infections present in themselves or in operating team members that were due to human immunodeficiency virus (29.4%), hepatitis B virus (27.8%), herpetic whitlow (28.6%), or paronychia caused by S. aureus (33.3%). PMID- 1869650 TI - Ultrastructural observations on 'foam cells' and the source of their lipid in verruciform xanthoma. AB - Verruciform xanthomas occur on mucocutaneous surfaces and are characterized by hyperkeratosis, acanthosis, and the occurrence of "foam cells" stuffed with lipid surrounding capillaries in the dermis between rete pegs. Ultrastructural examination of a lesion on the penis revealed the presence of melanocytes with many lipid droplets in the basal layer of the epidermis. We suggest that they are a major source of the lipid of the "foam cells." However, this study provides no information as to the nature or lineage of the "foam cells." PMID- 1869651 TI - A study of elastic tissue and actinic radiation in "aging," temporal arteritis, polymyalgia rheumatica, and atherosclerosis. The actinic storm in the modern world. AB - Solar radiation provokes a lifelong series of destructive changes in the supporting elastic tissues of "exposed" skin. Called actinic elastosis/lysis (or actinic "aging"), the sequence begins in early life as simple elastic hyperplasia, converts in middle life to progressive actinic elastotic degeneration, and, in late life, typically ends with a stage of resorption (elastolysis) and atrophy ("aged" skin). Superficial "exposed" arteries such as the temporal artery participate in the same sequence of degenerative elastotic changes, which, as in the skin, may provoke granulomatous responses in a few of the many subjects affected. In the case of the temporal artery, a contingent outcome may be giant cell (temporal) arteritis and its recognized systemic vascular expression, polymyalgia rheumatica. Actinic commotion at the surface of the body is often massive in degree and extent and may be expected to exert a deleterious autoimmune impact on the essential elastic tissues of the arterial system. For this reason, solar radiation should be recognized as a risk factor for other elastic-related vascular diseases, including atherosclerosis and aneurysms. Man-made radiations may be exacerbating the effects of predominant solar radiation. Of the many radiant bands that make up the actinic (electromagnetic) spectrum, little is known for certain about the identity of those that cause these prevalent disorders of elastic tissue. Until this void is filled, more care should be taken with solar and the other "safe" radiations. PMID- 1869652 TI - Treatment of mildly to moderately photoaged skin with topical tretinoin has a favorable psychosocial effect: a prospective study. PMID- 1869653 TI - Ten cases of chronic ulcerative stomatitis with stratified epithelium-specific antinuclear antibody. PMID- 1869654 TI - Pyoderma gangrenosum coexistent with the hemophagocytic syndrome. PMID- 1869655 TI - Group A streptococcus-induced bullous toxic shock-like syndrome. PMID- 1869656 TI - Pterygium inversum unguis. PMID- 1869657 TI - Earring-induced localized iron tattoo. PMID- 1869658 TI - Nonscalp hair infection caused by Microsporum canis in patient with acquired immunodeficiency syndrome. PMID- 1869659 TI - Angiosarcoma arising in Kaposi's sarcoma (pleomorphic Kaposi's sarcoma) in a patient with human immunodeficiency virus disease. Armed Forces Retroviral Research Group. PMID- 1869660 TI - Susceptibility of Staphylococcus aureus. PMID- 1869661 TI - The many faces and phases of borreliosis. I. Lyme disease. PMID- 1869662 TI - Cutaneous surgery and the pregnant patient. PMID- 1869663 TI - Eccrine sweat gland disorders. PMID- 1869664 TI - Erythema multiforme caused by lithium. PMID- 1869665 TI - Multiple pigmented nail bands during hydroxyurea therapy: an uncommon finding. PMID- 1869666 TI - Treatment of vitiligo with topical melagenine--a human placental extract. PMID- 1869667 TI - Digital exostosis arising on the second toe. PMID- 1869668 TI - Pruritus in HIV infection. PMID- 1869669 TI - Autoimmune bullous disease in a patient with HIV infection. PMID- 1869670 TI - Treatment of cytarabine acral erythema with corticosteroids. PMID- 1869671 TI - Cutaneous and subcutaneous neuroblastoma in children and adults: case reports and population study. PMID- 1869673 TI - The International Foundation for Dermatology. PMID- 1869672 TI - Kaposi's sarcoma in a patient with temporal arteritis treated with corticosteroid. PMID- 1869674 TI - Israel Zeligman. PMID- 1869675 TI - Clearing of epidermolysis bullosa acquisita with cyclosporine. PMID- 1869676 TI - Longitudinal melanonychia striata. PMID- 1869677 TI - Small malignant melanomas: clinicopathologic correlation and DNA ploidy analysis. PMID- 1869678 TI - Nuclear segmentation anomalies of neutrophils in neutrophilic dermatosis associated with myelodysplastic syndrome. PMID- 1869679 TI - A method for the determination of UVA protection for normal skin. PMID- 1869680 TI - Therapeutic use of cytokines in dermatology. AB - Cytokines are glycoproteins produced by many different cells. Via binding to specific receptors on target cells they regulate the activation, differentiation, and proliferation of immune and nonimmune cells. After injury keratinocytes synthesize and release cytokines such as interleukins, colony stimulating factors, and growth factors. In addition, a network of interacting cytokines appears to be crucial to maintain proper balance. Dysregulation may contribute to certain diseases, particularly those of infectious and autoimmune origin. Therefore many of these mediators appear to be promising candidates to treat infectious and malignant diseases. This article briefly discusses the most important cytokines. Newly developed regimens with cytokines to treat cutaneous disorders will be reviewed. PMID- 1869681 TI - Quantitative nailfold capillary microscopy in cutaneous and systemic lupus erythematosus and localized and systemic scleroderma. AB - Quantitative television microscopy of nailfold capillaries of the fingers was performed in 12 patients with cutaneous lupus erythematosus (six with discoid type and six with disseminated type), in six patients with localized scleroderma (two with circumscribed type, two with linear types, and two with atrophic type), in 10 patients with systemic lupus erythematosus, and in eight patients with systemic scleroderma. The following features were analyzed and compared with a control group (n = 15) of similar age: venous plexus visibility; density of capillaries; avascular fields; hemorrhages; giant capillaries; diameters of the transitional segment, the arterial, and the venous limbs; loop width; and flow stop caused by local cooling test. The patient groups with cutaneous lesions only showed no essential differences as compared with the controls. Patients with systemic scleroderma differed in almost every finding from the controls and from patients with localized scleroderma. Patients with systemic lupus erythematosus exhibited significant differences in several findings as compared with the controls and the cutaneous lupus erythematosus group, but there was overlap. PMID- 1869682 TI - Direct immunofluorescence microscopy of 1 mol/L sodium chloride-treated patient skin. AB - Patients with bullous pemphigoid and those with epidermolysis bullosa acquisita often demonstrate virtually identical clinical, histologic, and immunopathologic features. Although some patients can be distinguished by their pattern of circulating IgG anti-basement membrane zone antibody binding to 1 mol/L sodium chloride-split human skin, approximately 20% and 50% of bullous pemphigoid and epidermolysis bullosa acquisita patients, respectively, do not possess such antibodies. Hence this study sought to determine whether these patients can be distinguished by mapping the distribution of basement membrane zone immunoreactants in patient skin split in vitro by 1 mol/L sodium chloride. All sodium chloride-treated samples from patients with bullous pemphigoid (n = 8), epidermolysis bullosa acquisita (n = 4), or other bullous skin diseases (n = 6) contained a lamina lucida cleavage plane bounded by bullous pemphigoid antigen and laminin; moreover, treatment of patient samples was performed without loss of tissue substrate or in situ immunoreactants. Deposits of IgG were found on the epidermal side of sodium chloride-treated skin from 13 of 14 bullous pemphigoid samples; IgG deposits in bullous pemphigoid samples were exclusively epidermal in eight, epidermal and dermal in five, and solely dermal in one. In contrast, IgG was found exclusively on the dermal side of sodium chloride-treated samples from patients with epidermolysis bullosa acquisita. Although IgG mapping distinguished bullous pemphigoid and epidermolysis bullosa acquisita patients in 94% of these samples, the distribution of C3 in sodium chloride-treated patient skin was more variable and less predictive diagnostically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869684 TI - Amyopathic dermatomyositis (dermatomyositis sine myositis). Presentation of six new cases and review of the literature. AB - We report six patients with the classic cutaneous findings of dermatomyositis who did not develop clinical or laboratory evidence of muscle disease for at least 2 years after onset of their skin manifestations. Such patients represent 11% of our total experience with dermatomyositis patients during a 15 year period. All six patients had Gottron's paules, periungual erythema/telangiectasia, and violaceous discoloration of the face, neck, upper chest, and back at some time during the course of their disease. In addition, all complained of pruritus and photosensitivity. None of the patients had evidence of malignancy. Each of five patients treated with oral corticosteroids for their cutaneous disease had marked improvement and did not develop myositis. These cases further emphasize that the cutaneous manifestations of dermatomyositis are pathognomonic of this disease and challenge the commonly held notion that muscle disease always develops within 2 years of onset of skin disease. PMID- 1869683 TI - Salt-split human skin substrate for the immunofluorescent screening of serum from patients with cicatricial pemphigoid and a new method of immunoprecipitation with IgA antibodies. AB - In patients with cicatricial pemphigoid, immunoglobulins (usually IgG) and complement are deposited within the dermoepidermal junction and are detected by direct immunofluorescent staining of perilesional mucous membrane and/or skin with fluorescein-labeled antibodies to human immunoglobulins. Although rare, some patients also have circulating low-titer, anti-basement membrane zone autoantibodies. In this study, we report 11 patients with the clinical, histologic, and immunologic criteria for cicatricial pemphigoid who had circulating anti-BMZ autoantibodies as demonstrated by positive indirect staining of a normal human skin that had been fractured through the dermoepidermal junction by prolonged incubation in a cold, 1 mol/L sodium chloride solution. On this salt-split human skin substrate, 9 of the 11 patients (82%) had autoantibodies that bound to the epidermal roof, one serum stained only the dermal floor, and one serum stained both sides of the separation. The predominant class of immunoglobulin in the patients' sera that bound to the substrate was IgA; IgA was the single immunoglobulin in 55% and was associated with IgG in 18%. IgG was the only immunoglobulin detected in 27% of the cases. No specific protein was detected by either Western immunoblot or a new IgA immunoprecipitation procedure. PMID- 1869685 TI - Antibodies to neutrophil cytoplasmic antigens: serologic marker for Sweet's syndrome. AB - Seven patients with a clinical and histologic diagnosis of Sweet's syndrome were tested for the presence of circulating antibodies to neutrophil cytoplasmic antibodies. Six of the seven patients had detectable antibodies to neutrophil cytoplasmic antibodies at a serum dilution of at least 1:20. Antibodies to neutrophil cytoplasmic antibodies were not found in serum from patients with a range of cutaneous diseases, some known to cause clinical or histologic confusion with Sweet's syndrome. The detection of circulating antibodies to the neutrophil cytoplasm may be of possible diagnostic value in Sweet's syndrome. PMID- 1869686 TI - Staphylococcal sepsis in HIV antibody seropositive psoriasis patients. AB - The cases of three HIV-positive men with generalized psoriasis and staphylococcal sepsis are reported. In each case the skin appeared to be the source of infection. While the patients received antibiotic therapy, the psoriatic plaques resolved despite minimal or no topical treatment. PMID- 1869687 TI - Gypsy moth caterpillar dermatitis--revisited. AB - Gypsy moth caterpillar dermatitis is a pruritic, papular, urticarial eruption on exposed skin that occurs most commonly after direct contact with the first instar larva of the gypsy moth (Lymantria dispar). We present two case reports to illustrate its clinical and histopathologic features. Both cases occurred during the spring of 1990 and coincided with the greatest infestation of L. dispar in the Northeast to date. The pathogenesis of this distinctive gypsy moth dermatitis most likely involves histamine release by the caterpillar and a delayed hypersensitivity reaction in its host. PMID- 1869688 TI - Cicatricial pemphigoid. AB - Cicatricial pemphigoid is a subepidermal blistering disease that involves the mucous membranes and the skin. The oral cavity and the eye are most frequently involved. The clinical course is of long duration, and often there is significant scarring that can have devastating sequelae. The majority of the patients are elderly. The disease is characterized by the in vivo deposition of an anti basement membrane zone antibody. The anti-basement membrane zone antibody cannot be detected in the circulation by routine laboratory techniques. The pathogenesis is poorly understood, and the cause is not known. Cicatricial pemphigoid may remain localized to the oral cavity or the eye or the skin (Brunsting-Perry variety), or it may be generalized. It rarely occurs in children, and it may be drug induced. Efforts must be made to differentiate cicatricial pemphigoid from bullous pemphigoid, epidermolysis bullosa acquisita, linear IgA bullous disease, and other vesiculobullous disease. Early recognition and treatment can improve the prognosis and avoid surgical intervention. Topical therapy is beneficial and expedites healing. Intralesional corticosteroids are effective and can help reduce the dose of systemic steroids. Most patients require systemic corticosteroid therapy. Dapsone is also useful in treating cicatricial pemphigoid, especially in patients in whom systemic steroids are ineffective or in whom they have to be discontinued because of side effects. Immunosuppressive agents (azathioprine or cyclosphosphamide) are indicated in patients with progressive disease. Occasionally both drugs may be needed. PMID- 1869689 TI - Acute and chronic urticaria and angioedema. AB - Urticaria and angioedema are clinical manifestations of various immunologic and inflammatory mechanisms, or they may be idiopathic. The respiratory and gastrointestinal tracts as well as the cardiovascular system may be involved in any combination. Patients with urticaria and/or angioedema can be classified based on pathophysiologic mechanisms into those with IgE-dependent or complement mediated immunologic disorders, those with nonimmunologic disorders in which there is a direct effect on the mast cell or on arachidonic acid metabolism, and those whose condition is idiopathic. Evaluation of patients should focus on a thorough history. Laboratory tests provide minimal additional information. About one half of patients with urticaria alone and 25% with urticaria and angioedema or angioedema alone are free of lesions within 1 year. With urticaria, angioedema, or both, 20% of patients experience episodes for more than 20 years. PMID- 1869690 TI - Angioedema: manifestations and management. AB - Angioedema is characterized by localized swelling of sudden onset affecting the skin and/or mucous membranes. It can be classified into hereditary and acquired forms. Hereditary angioedema is a rare disease inherited as an autosomal dominant trait and caused by a deficiency of C1-esterase inhibitor. Acute attacks are life threatening and cannot be managed by antihistamines, corticosteroids, or adrenergic drugs. Prophylactic therapy is possible with danazol or stanozolol. Acquired angioedema includes nonhereditary C1-esterase inhibitor deficiency; idiopathic, allergic, and drug-induced forms; angioedema associated with lupus erythematosus and hypereosinophilia; and angioedema caused by physical stimuli. Treatment of these forms of angioedema depends on identifying and avoiding the cause, induction of tolerance, or symptomatic treatment with systemic antihistamines. PMID- 1869691 TI - Urticaria and angioedema: diagnosis and evaluation. AB - Because urticaria clears spontaneously in most patients, an extensive workup is not advised during the early weeks of an urticarial eruption. Whether and when to perform a screening workup or a more extensive workup depend on the degree of suspicion that the patient is ill, the urgency with which the patient presses for an answer, and the presence or absence of signs or symptoms that might lead the physician to pursue a diagnosis other than chronic idiopathic urticaria. Angioedema may occur with urticaria, and when it does, the prognosis is worse. Whereas urticaria manifests as circumscribed edema involving the superficial dermis, angioedema involves primarily the deep dermis or subcutaneous or deeper layers. Individual urticarial lesions usually disappear within 2 to 4 hours, whereas those of angioedema can persist for 72 hours. The workup for patients with chronic angioedema can be similar to that for patients with urticaria. However, several additional diagnostic possibilities should be pursued in patients with angioedema, such as hereditary angioedema caused by C1-esterase inhibitor deficiency, because anabolic steroids are effective in the treatment of these conditions. PMID- 1869692 TI - Mast cells and their role in urticaria. AB - Mast cells are the primary effector cell type in urticaria and angioedema. Recognition of different types of mast cells has increased the understanding of their cell biology and may help refine the therapy of human allergic diseases. Mast cells containing chymase and tryptase (MCTC) and tryptase alone (MCT) are two distinct types distinguished on the basis of the neutral protease composition of their granules. MCT cells are distributed primarily in the lung and gastrointestinal mucosa, whereas MCTC cells lie primarily in skin and gastrointestinal submucosa. The appearance of MCT cells in intestinal tissue is T lymphocyte dependent, whereas MCTC cells is not. The granules in unstimulated mature MCT cells typically contain complete scrolls, whereas those of MCTC cells often contain grating or lattice substructures. Major categories for the mediators of mast cells include performed mediators present in the secretory granule, newly generated lipid-derived mediators, and cytokines. PMID- 1869693 TI - Changes in lipid and carbohydrate metabolism during starvation in adult Manduca sexta. AB - Adult Manduca sexta feed very irregularly in the laboratory, and many adult males never feed. Feeding adults live longer and feeding females lay many more eggs; however, in both feeding (sugar water) and starving adults a decrease of metabolic reserves is observed. Carbohydrates disappear from hemolymph and from fat body. Fat body lipid also decreases, while hemolymph lipid concentration increases strongly in starving adults. The activity of fat body glycogen phosphorylase increases strongly in starving adult M. sexta. The activity of glycogen phosphorylase is correlated inversely with hemolymph sugar concentration. Injected trehalose inactivates glycogen phosphorylase within 2 h. and lowers the hemolymph lipid level within 6 h. In starving adult M. sexta, neither the activation of glycogen phosphorylase nor the increase of hemolymph lipid concentration depends on adipokinetic hormone, since cardiacectomy does not prevent the activation of glycogen phosphorylase nor the increase of hemolymph lipid level. PMID- 1869694 TI - Adaptation of homeostatic thermoregulation: comparison of incubating and non incubating bantam hens. AB - Incubating and non-incubating Bantam hens were exposed to identical thoracic skin cooling to study the difference between their physiological responses with regard to thermoregulatory adaptation to incubation. Under resting conditions thoracic skin temperature (Tths) and metabolic heat production (M) were significantly higher in broody than in non-broody hens, indicating a permanently increased conductance of the brood patch. Thoracic skin cooling from 35 to 25 degrees C decreased Tths less in broody than in non-broody hens. In broody hens, these coolings induced a large, immediate increase in M, no constriction of brood patch vasculature, and a decrease in colonic temperature (Tc). This decrease in Tc triggered no further increase in M, but induced vasoconstriction in the feet. The coolings induced a smaller increase in M in the non-broody hens, accompanied by pronounced vasoconstriction, and did not affect Tc and foot temperature, Tf. The effects of more severe thoracic skin cooling (between 25 and 15 degrees C) differed much less between non-broody and broody hens. Vasoconstriction of the brood patch also occurred in the latter. It is concluded that in adaptation to incubation the thoracic skin becomes more sensitive, and its input signal becomes stronger for the control of certain effector systems of thermoregulation, allowing a controlled heat transfer to the eggs. PMID- 1869695 TI - Absorption of bioactive human growth hormone after oral administration in the common carp (Cyprinus carpio) and its enhancement by deoxycholate. AB - Recombinant human growth hormone was administered orally to carp and serum levels of absorbed bioactive hormone were investigated using a highly sensitive Nb2 rat lymphoma cell bioassay and radioimmunoassay. Serum levels of bioactive hGH reached maximum values 30 min after oral intubation and then gradually decreased. Co-administration of the hormone with deoxycholate to fasted carp resulted in up to a 1000-fold increase in absorption compared to aqueous solutions of the hormone, but had no effect on the kinetics of the absorption process. Absorption of the hormone in starved fish was significantly greater than in fed fish. A linear dose-response relationship was observed for hGH in starved fish and the level of absorption in fed fish was influenced by the time interval from the last meal. The ratio of bioactive to immunoactive hGH in fasted fish indicated little loss of bioactivity and also that deoxycholate may be protective against hGH degradation. The present study demonstrates for the first time that biologically active hGH is absorbed in the common carp after oral intubation. Furthermore, the use of a biological detergent dramatically increased the extent of hGH absorption. Additional studies are required to establish the appropriate conditions (diet composition, feeding level, and frequency, etc.) in which polypeptide hormones could be introduced orally to fish. PMID- 1869696 TI - Gestational changes in electrolyte transport, electrical activity, and permeability of the porcine placenta. AB - 1. The electrolyte transport capacities of the porcine placenta and fetal membranes (amnion, chorion, and allantois) during gestation (47-112 days) were assessed in vitro and in the absence of electrochemical, osmotic, or hydrostatic driving forces. Net transmural transport of 22Na and 36Cl across sections of porcine allantochorion-endometrium (ALCE), amniochorion-endometrium (AMCE), and allantoamnion (AA) mounted in Ussing chambers could not be detected at any stage of gestation. 2. These tissues were characterised throughout gestation by low electrical potential difference (PD; less than 5 mV, fetal side positive with respect to maternal side) and short circuit current (SCC; less than 16 microA.cm 2) which were amiloride and iodoacetate sensitive. 3. A periparturitent reversal in the polarity of PD to fetal side negative and a change in the direction of the SCC was observed in tissues obtained from sows (n = 3) at 111-112 day gestation. These changes were accompanied by a 73% increase in electrical resistance (R) and a 2-10-fold decrease in the permeability of tissues to Na and Cl. 4. Morphological studies revealed a decrease in the thickness of allantoamnion and a decrease in the height of epithelia from ALCE, AMCE, and AA during gestation, indicating a decrease in activity. These morphological changes only partly explained the pre-term electrophysiological changes in these tissues. PMID- 1869698 TI - [True place of simple sugars in the cause of caries]. AB - A recent leaflet published for dental patients by the Canadian Association of Confectioners promotes the consumption of sweets, considering them on an equal basis, in regard to caries, as any other foods containing simple sugars, such as: fruits, vegetables, bread or pasta. This article intends to demistify such inference. While it is true that most foods containing simple sugars can lower plaque pH when considered alone, in the context of a total diet, the relationship between simple sugars and caries is much more complex. Also, in regard to total health, one can not equate all simple sugars since they differ considerably in terms of nutritional value. PMID- 1869697 TI - [Comparison of different types of cleft lip and palate in regards to dental anomalies and sexual incidence]. AB - The present study addresses two questions. Does the incidence of dental anomalies differ among the four following types of cleft lip and palate: the isolated cleft palate, the unilateral cleft lip and palate, (right or left), and the bilateral cleft lip and palate. Furthermore is the sexual incidence comparable among the four above mentioned types? Radiographic records and complete family history of clefting of 156 patients with a complete cleft lip and palate were obtained from the Cleft Lip and Palate Teams of Ste-Justine Hospital. Patients in which the cleft was part of a syndrome were excluded from the study. According to the analysis of the data, the incidence of dental anomalies was relatively high, specifically as high as 92% for the bilateral cleft lip and palate. The sexual incidence differed among the four types. PMID- 1869699 TI - Medical College of Georgia AIDS case. PMID- 1869700 TI - Funding, survival and growth of postdoctoral general dentistry programs after federal funding ends. PMID- 1869701 TI - The Advanced Education in General Dentistry program at the University of Maryland at Baltimore. PMID- 1869702 TI - University of California at San Francisco: a combined GPR/AEGD model. PMID- 1869703 TI - The San Antonio AEGD/GPR model: historical and financial perspectives. PMID- 1869704 TI - North Carolina AEGD model. AB - The financial resource and expense management experience of the University of North Carolina Advanced Education in General Dentistry program has been presented. The program relies heavily on clinic productivity and effective financial management to counter challenges imposed by a diminishing state budget appropriation to the School of Dentistry and the lack of financial flexibility within the state university system. The School of Dentistry is firmly established and highly regarded within the university; administrative support for the program from within the school has been substantial and is ongoing. The program continues to actively pursue external funding applications; nonetheless, resource augmentation to date has been a largely internal matter through maximal and efficient use of existing means. PMID- 1869705 TI - Summary analysis of financial strategies for postdoctoral general dentistry programs. PMID- 1869706 TI - A postdoctoral year for the practice of dentistry: rationale and progress. PMID- 1869707 TI - Navigating an educational program through the treacherous 90s: dynamics of the health-care system. PMID- 1869708 TI - General practice residency programs: benefits to residents and patients. PMID- 1869709 TI - Postdoctoral oral and maxillofacial radiology. PMID- 1869710 TI - Nurses with degrees in the United Kingdom: careers and contributions and challenges. PMID- 1869711 TI - Researching needs in district nursing. AB - This paper describes the first stage of a research project aimed at understanding the needs of clients (and their carers) of district nursing services. The project applies a pluralistic research design, combining qualitative and quantitative methods. Through the use of an ethnographic approach, concepts of needs are generated which are related to how clients and carers perceive themselves and the role of the district nurse. The study attempts to formulate needs within a contextual framework against which an activity analysis of district nurses' work (stage 2) can be evaluated. PMID- 1869712 TI - A symbolic awareness context identified through a grounded theory study of health visiting. AB - The purpose of the study, which is not yet complete, was one of theory building or conceptualization. This was needed because of a lack of information about how health visitors identify which approach to use within any particular situation. An overview of the method of grounded theory explains how data were collected and analysed. Then, one major aspect of the emerging theory--a symbolic awareness context which seems to surround and influence interactions between health visitors and their clients--is outlined. The analysis suggests that, when the interaction is examined in context, any one question, purpose or topic selected by health visitor or client as a specific focus, forms only a relatively small component part of the whole. Strategies which enhance openness and consonance within the context are detailed. The awareness context has implications for health visiting practice and organization. PMID- 1869713 TI - Caring versus empowerment: considerations for nursing practice. AB - The authors argue that there is a tension between the concepts of caring and empowerment. This tension appears in political and managerial debates over how best to run a health service, and it reappears in the clinical situation in nursing dilemmas over the presentation of information to patients. The authors review the major contributions to theory from health care literature, and use case studies to explore some of the clinical implications of these theories for nursing practice. PMID- 1869714 TI - The size of the pressure-sore problem in a teaching hospital. AB - A series of three prevalence surveys were undertaken in a teaching hospital (where medical students are taught) in the West Midlands of England to identify the numbers of patients at risk of developing pressure sores and the actual number of patients with pressure sores, prior to the purchase of pressure relieving equipment. All in-patients were assessed using the Waterlow score. Full details of all pressure sores and any pressure-relieving equipment in use was recorded. There was a mean pressure sore prevalence of 7.32%, the prevalence for each survey being 8.77%, 5.1% and 8.1% respectively. Grades 2 and 3 were the most commonly reported grades and the sacrum was the most frequent position. It was anticipated that there would be a difference in dependency between the patient populations in each of the three surveys. This was not so and, when using the Waterlow score, the numbers of patients found to be at no risk, at risk and at high risk remained remarkably stable. Only those in the very high risk category fluctuated. It is postulated that the difference between the prevalence in the three surveys is related to the difference in the numbers of patients seen to be at very high risk. These surveys have provided a basis for selecting pressure relieving equipment and baseline information for monitoring the efficacy of the prevention programme. PMID- 1869715 TI - Theories of self-care: their relevance to chemotherapy-induced nausea and vomiting. AB - Nausea and vomiting are reputed to be two of the most disruptive side-effects associated with chemotherapy. Pharmacological and behavioural interventions are well described in the literature, but sparse attention appears to have been focused upon the role of self-care. This paper outlines the problem of chemotherapy-induced nausea and vomiting. The concept of self-care is described, including possible motivations to perform self-care, and potential relationships between symptom perception and self-care are noted. It concludes with suggestions for theoretical work and future research studies concerning self-care behaviour for nausea and vomiting induced by chemotherapy. PMID- 1869716 TI - Factors which influence how nurses communicate with cancer patients. AB - Communication is one of the most important aspects of cancer nursing. Evidence suggests nurses experience communication difficulties and frequently block patients from divulging their worries or concerns. This paper focuses on a study which aimed to determine: (a) the extent to which nurses facilitate or block patients and awareness of their verbal behaviours; (b) whether there is a relationship between nurses' verbal behaviours and levels of anxiety, social support, work support and attitude to death; and (c) nurses' difficulties in caring for cancer patients. The study was conducted in a specialist and non specialist hospital. Fifty-four registered nurses completed three audio-taped histories (one with a new cancer patient, a patient with a recurrence and a patient for pallative care), a self-administered questionnaire and a semi structured audio-taped interview. The data were analysed using SPSSX. The findings indicate an overall poor level of facilitative communication, with a patient's recurrence causing most difficulties. There is evidence to suggest the way nurses communicate may depend on the environment created by the ward sister, the nurses' religious beliefs and attitude to death rather than specific education in communication skills. PMID- 1869717 TI - Symptom patterns in women with premenstrual syndrome complaints: a prospective assessment using a marker for ovulation and screening criteria for adequate ovarian function. AB - This study examined the symtom patterns of women seeking help for Premenstrual Syndrome (PMS) complaints. Seven women who were less than 35 yrs, within 10% of ideal body weight and who had experienced a full-term pregnancy, completed a daily health diary during an ovulatory menstrual cycle. In the luteal phase, symptom summary scores of the PMS group increased (P less than 0.05) and were markedly higher (P less than 0.5) from baseline acyclic scores of four ovulatory women who denied menstrual-related distress. To examine severity changes in individual symptoms, a total of 399 cases representing 57 symptoms from the seven 45-day diaries were evaluated for menstrual cycle entrainment. Of the 246 symptoms that met the criteria for a cycle phase change (62%), the classic PMS pattern of low/high severity was the most common (40%). Seven different subtypes of the PMS pattern were identified; four of these subtypes demonstrated a severity score elevation at ovulation as well as during the premenstruum. For individual women, the majority of symptoms (65%) displayed only two pattern types, suggesting a common rhythmic entrainment of symptom intensity. PMID- 1869718 TI - Relaxation: episiotomy incisional pain and overall discomfort. AB - The primary purpose of this study was to determine the effect of a simple relaxation technique on postpartum patients' episiotomy incisional pain and overall discomfort. This study was carried out through the use of a posttest-only experimental design. A total of 40 subjects (20 in the experimental group and 20 in the control group) participated in the study. Only the experimental group was taught the relaxation technique and told to use it whenever they had pain or discomfort in their episiotomy incision. Within 24 hours after delivery, all subjects rated their episiotomy pain and overall discomfort on the scales of pain and discomfort. Twenty-four hours after delivery, a chart review was done on each subject to further measure pain by amount and frequency of analgesic use. Paired t-tests were used to examine the differences between the means of the experimental and control groups for subjects' pain as measured by amount of pain and amount of analgesic use, and amount of overall discomfort. Chi-square analysis was utilized to examine the differences between the experimental and control groups for subjects' amount of pain as measured by frequency of analgesic use. Results of the analyses demonstrated that for the subjects who used the relaxation technique, there was a general trend for decreased pain and discomfort. PMID- 1869719 TI - Immigrant women speak of chronic illness: the social construction of the devalued self. AB - This inquiry into the existential experience of chronic illness by immigrant women begins from a phenomenological perspective, and proceeds to examine the context in which women's experiences are embedded. It is argued that multiple factors influence the ability to manage illness. Not least among them are the emotions that are an integral part of daily existence, and the sense of self that is constructed during the course of a chronic illness. These emotions, and the definitions of self embodied within the illness experience, are produced in ongoing social interactions. For the immigrant woman, the difficulties in living with a chronic illness are exacerbated by the experience of uprooting from her homeland and resettling in a new country. She must deal with her marginality, social isolation and alienation in a foreign culture. The feeling of being devalued arises not only from the chronic illness experience, but also from the definition of self that is constructed in dealing with the migration experience. The implications that this research study has for the profession of nursing are discussed. PMID- 1869720 TI - In search of more complete answers to research questions. Quantitative versus qualitative research methods: is there a way forward? AB - This paper presents an overview of research methods utilized in nursing to date and traces the origins of the schism in nursing research which has led to the development of the quantitative-qualitative research-methods dichotomy. The philosophical and technical characteristics which distinguish these apparently opposing methodologies are described and critically discussed. The use of triangulation of different methods and types of data is suggested as an alternative research strategy. A study which used triangulation as a research approach which examined newly registered nurses' attitudes and educational preparation to care for patients with cancer, and developed and evaluated an educational intervention for nurses on cancer care, is described. This illustrates how the use of different research methods within a single study can provide a richer and deeper understanding of the area under investigation than would otherwise be possible. This paper also discusses the notion that nursing research has arrived at a watershed in which competing methodologies serve to divide and separate nurse researchers on the grounds of philosophical approach, a division which a neophyte discipline such as nursing can ill afford. Nurse researchers need to gain skills and understanding of different approaches to capitalize on the strengths and benefits of each in order to develop a more complete understanding of nursing practice in all its complexity. PMID- 1869721 TI - A participant observation study of power relations between nurses and doctors in a general hospital. AB - The problem addressed in this paper is how nurse-doctor power relations are manifested in a hospital setting. A review of the literature identified four major ideal types of interaction between nurses and doctors in decision-making processes. These were unproblematic subordination, informal covert decision making, informal overt decision making and formal overt decision making on the part of nurses. Each of these types was tested against empirical data gained from participant observation of interactions between the nurses and doctors working in an intensive care unit and a general medical ward. It was concluded that while both the unproblematic subordination and the informal covert decision-making types of interaction appeared superficially to be used frequently, closer examination revealed that, with the exception of nurse-consultant interactions, nurses were less dependent on these subordinate modes of interaction than much of the literature suggested. Formal overt decision making, despite official encouragement, was also infrequently utilized. However, it was noticed that senior nurses especially used informal overt strategies to involve themselves in decision-making sequences. Use of such strategies had the effect of reducing though not eliminating the power differential between doctors and nurses. PMID- 1869722 TI - Role conflict in student nurses: towards a positive approach for the 1990s. AB - This review paper seeks to adopt a constructive approach towards the subject of the role conflict experienced by student nurses. The significance of role conflict is explored, as are its causes and its effects on the student. Role conflict is then discussed from the perspectives of social psychology in general and nursing in particular, and the paper concludes with an emphasis on the role of the nurse educator in helping the students deal actively and constructively with the role conflict that they will inevitably experience during their careers in nursing. PMID- 1869724 TI - Power: a concept analysis. AB - This paper follows the Walker & Avant approach to concept analysis of the concept of power. For the purposes of the paper, power was defined as the actual or potential ability or capacity to achieve objectives through an interpersonal process in which the goals and means to achieve the goals are mutually established and worked toward. The distinction between the views of power as 'power to' versus 'power over' are addressed in the literature review. King's conceptual framework was used as a guide. Defining attributes, antecedents and consequences of power, demonstration cases, and assumptions are presented. A theorem and testable hypothesis are proposed. The final product is a conceptual map which illustrates the contents of the concept analysis. PMID- 1869723 TI - What makes nursing satisfying: a comparison of college students' and registered nurses' views. AB - This paper reports a study of nurses' perceptions of the positive and negative features of the work environment and their contribution to satisfaction with nursing. The concept of a 'work space' was developed to describe nurses' mental images of the features of their work environment. Eighty-four final-year student nurses and 75 registered nurses rated questionnaire items designed to examine perceptions of opportunities for professional development, sources of satisfaction, difficulties, time constraints and problematic interactions with other hospital personnel. There was general agreement among nurses about the aspects of their work that they found satisfying, but student nurses were more pessimistic than registered nurses that nursing would give them opportunities for recognition of their worth. Students returning from practica in critical care wards reported more stressful interactions with other personnel than students returning from general ward practica. Structural equation modelling of the causal relations between sources of satisfaction with nursing revealed that recognition and self-perceptions of work as a nurse were the strongest predictors of overall satisfaction with nursing. Caring for patients contributed only indirectly through its influence on nurses' feelings about themselves. The data indicate the significance of personal and social implications of nursing careers. PMID- 1869725 TI - Restenosis after coronary angioplasty: a multivariate statistical model to relate lesion and procedure variables to restenosis. The M-HEART Investigators. AB - The Multi-Hospital Eastern Atlantic Restenosis Trial group obtained follow-up angiography in 510 patients with 598 successfully dilated coronary lesions who were enrolled in a controlled trial of the effects of a single dose of 1 g of methylprednisolone on restenosis after coronary angioplasty. The overall restenosis rate was 39.6%. The strongest univariate relations to the restenosis rate were found for lesion location (saphenous vein graft, 68%; left anterior descending artery, 45%; left circumflex artery and right coronary artery, 32%; p = 0.002); lesion length (less than or equal to 4.6 mm, 33%; greater than 4.6 mm, 45%; p = 0.001); percent stenosis before angioplasty (less than or equal to 73%, 25%; greater than 73%, 43%; p = 0.005), percent stenosis after angioplasty (less than or equal to 21%, 33%; greater than 21%, 46%; p = 0.017) and arterial diameter (less than 2.9 mm, 44%; greater than or equal to 2.9 mm, 34%; p = 0.036). Two multivariate models to predict restenosis probability were developed with use of stepwise logistic regression. The preprocedural model, which included only variables whose values were known before angioplasty, entered lesion length, vein graft location, left anterior descending artery location, percent stenosis before angioplasty, eccentric lesion and arterial diameter. The postprocedural model, which also included variables whose values were known after angioplasty was performed, was similar to the preangioplasty model except that it also entered postangioplasty percent stenosis and "optimal" balloon sizing but did not enter eccentric lesion. These data indicate that the probability of restenosis after angioplasty is determined predominantly by the characteristics of the lesion being dilated. They are consistent with the known intimal proliferative mechanism of restenosis, offer a means of identifying lesions at unusually high or low risk of restenosis, and of predicting the likelihood that a particular lesion will restenose after angioplasty and provide a rationale for stratification by restenosis probability in the design of future studies of restenosis. PMID- 1869726 TI - Effect of age on use of thrombolytic therapy and mortality in acute myocardial infarction. The MITI Project Group. AB - The findings in 3,256 consecutive patients hospitalized for acute myocardial infarction were tabulated to assess the history, treatments and outcome in the elderly; 1,848 patients (56%) were greater than 65 years of age, including 28% who were aged greater than or equal to 75 years. The incidence of prior angina, hypertension and heart failure (only 3% of patients less than 55 years of age had a history of heart failure compared with 24% greater than or equal to 75 years old) was found to increase with age. Twenty-nine percent of patients less than 75 years of age were treated with a systemic thrombolytic drug compared with only 5% of patients older than 75 years. Mortality rates increased strikingly with advanced age (less than 2% in patients less than or equal to 55, 4.6% in those 55 to 64, 12.3% in those 65 to 74 and 17.8% in those greater than or equal to 75 years). Both the incidence of complicating illness and a nondiagnostic electrocardiogram (ECG) increased with age. In a multivariate analysis of outcome in older patients (greater than or equal to 65 years), adverse events were related to both prior history of heart failure (odds ratio 3.9) and increasing age (odds ratio 1.4 per each decade of age). Outcome was not improved by treatment with thrombolytic drugs, but these agents were prescribed to only 12% of patients greater than 65 years of age, thereby reducing the power for detecting such an effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869727 TI - A case for early surgery in native left-sided endocarditis complicated by heart failure: results in 203 patients. AB - From January 1982 to December 1988, 203 consecutive patients were selected for early valve replacement (mean 10 days from time of admission) if they had clinical evidence of native valve endocarditis with 1) vegetations on echocardiography, 2) severe valvular lesions, and 3) heart failure. Surgery was performed within 7 days of admission in 56% of patients and was done urgently because of hemodynamic deterioration in 108 (53%). All vegetations were identified by echocardiography and confirmed macroscopically at surgery. One hundred ten patients had isolated aortic valve infection, 50 had isolated mitral valve infection (p less than 0.05 for aortic vs. mitral) and 43 had double-valve infection. Mean aortic cross-clamp time was 57, 38 and 67 min, respectively. Sixty-four patients (32%) had extensive infection involving the anulus or adjacent tissues, or both; such infection more frequently involved the aortic than the mitral valve (p less than 0.05). Thirty-eight patients (35%) with aortic valve infection had abscess formation compared with 1 patient (2%) with mitral valve infection (p less than 0.05). Only eight patients (4%) died in the hospital. There were seven patients (3%) with a periprosthetic leak and five patients (3%) with early prosthetic valve endocarditis. Long-term follow-up, available in 174 hospital survivors (89%), revealed 10 deaths and two new ring leaks at 38 +/- 22 months. In conclusion, among patients with endocarditis who need surgery for heart failure, aortic valve infection is more prevalent than mitral valve infection and is more often associated with extensive infection, including abscess formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869728 TI - Early surgery for native left-sided endocarditis. PMID- 1869729 TI - Irregular coronary lesion morphology after thrombolysis predicts early clinical instability. AB - After successful thrombolytic treatment for acute myocardial infarction, recurrent ischemia and infarction may occur with little warning. Coronary lesion morphology was analyzed from angiograms performed in 72 consecutive patients at 1 to 8 days after streptokinase treatment for acute myocardial infarction and the data were evaluated in relation to the subsequent clinical course. All patients were clinically stable at the time of angiography and continued to receive heparin infusion for greater than or equal to 4 days after thrombolysis. The infarct-related artery was patent in 55 patients (76%). In the 10 days after angiography, 15 patients developed prolonged episodes of angina at rest; the condition of 4 stabilized with medical treatment, but 11 required urgent medical intervention (coronary angioplasty in 8 and bypass surgery in 3). There were no differences in age, gender, left ventricular function or extent of coronary artery disease between those patients who developed unstable angina and those who had a stable in-hospital course. However, the median plaque ulceration index of the infarct-related lesion was 6.7 (95% confidence limits 6.3, 10) in the 15 patients with an unstable course versus 3.3 (2, 4.4) in those with a stable course (p less than 0.001). There were no differences between the two patient groups in the severity of stenosis, length of diseased segment, symmetry/eccentricity, presence of a shoulder, location at branch point or bend, presence of globular or linear filling defects, contrast staining or collateral supply. These data show that after thrombolysis, the degree of irregularity of the infarct-related artery is a critical determinant of early clinical instability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869730 TI - Prognostic implications of lesion irregularity on coronary angiography. PMID- 1869731 TI - Prognostic significance of a predischarge exercise test in risk stratification after unstable angina pectoris. AB - The prognostic significance of exercise testing was compared with clinical and electrocardiographic (ECG) variables in a prospective study of 107 patients with unstable angina discharged from the hospital on medical therapy. During a follow up period of 12.8 +/- 1.4 months, 10 patients (9%) had a nonfatal myocardial infarction (n = 8) or died (n = 2) and 22 (20%) were readmitted with recurrent unstable angina. The relation between 20 clinical, ECG and exercise test variables and the risk of adverse outcome (death, nonfatal myocardial infarction or recurrent unstable angina) was analyzed using both univariate and multivariate (logistic regression) analysis. Univariate predictors of adverse outcome included diabetes mellitus, evolutionary T wave changes, T wave changes on the preexercise ECG and low maximal rate-pressure product during exercise. Independent predictors of adverse outcome in multivariate analysis included diabetes mellitus, evolutionary T wave changes after admission, rest pain during hospitalization, ST depression during exercise and low maximal rate-pressure product. A predictive model constructed using the regression equation and all independent predictors stratified patients into high and low risk groups (41% and 5% risk of adverse outcome, respectively). The result of a predischarge exercise test adds independent prognostic information to clinical and ECG data in medically treated patients with unstable angina and could be used in combination with clinical and ECG data to identify patients at risk of adverse events. PMID- 1869732 TI - Vagaries of predischarge exercise stress testing in acute myocardial ischemic syndromes. PMID- 1869733 TI - Seminar on cardiovascular manifestations of the toxic oil syndrome and related conditions. PMID- 1869734 TI - Toxic oil syndrome: a current clinical and epidemiologic summary, including comparisons with the eosinophilia-myalgia syndrome. AB - In the spring and summer of 1981, an epidemic of a new illness now referred to as the toxic oil syndrome occurred in central and northwestern Spain, resulting in some 20,000 cases, 12,000 hospital admissions and greater than 300 deaths in the 1st year of the epidemic. The initial onset of illness was usually acute, and patients presented primarily with a respiratory syndrome involving cough, fever, dyspnea, hypoxemia, pulmonary infiltrates and pleural effusions. While approximately 50% of patients recovered from this acute phase of the illness without apparent sequelae, the remaining patients developed an intermediate or chronic phase, or both, of illness involving severe myalgia, eosinophilia, peripheral nerve damage, sclerodermiform skin lesions, sicca syndrome, alopecia and joint contractures, among other findings. Epidemiologic and analytic chemical studies have clearly linked the toxic oil syndrome to the ingestion of oil mixtures containing rapeseed oil denatured with aniline. However, the precise identity of the etiologic agent within this oil has never been determined. Aniline itself did not cause the illness, but the causal agent may be a reaction product of aniline with some oil component. Although many aspects of disease activity in the involved patients have lessened with time, the ultimate consequences of their disease are not clear and are the subject of ongoing study. The recently described eosinophilia-myalgia syndrome in the United States clinically resembles the toxic oil syndrome. PMID- 1869735 TI - Intravenous adenosine: continuous infusion and low dose bolus administration for determination of coronary vasodilator reserve in patients with and without coronary artery disease. AB - To assess the use of adenosine as an alternative agent for determination of coronary vasodilator reserve, hemodynamics and coronary blood flow velocity were measured at rest and during peak hyperemic responses to continuous intravenous adenosine infusion (50, 100 and 150 micrograms/kg per min for 3 min) and intracoronary papaverine (10 mg) in 34 patients (17 without [group 1] and 17 with [group 2] significant left coronary artery disease), and in 17 patients (11 without and 6 with left coronary artery disease) after low dose (2.5 mg) intravenous bolus injection of adenosine. The maximal adenosine dose did not change mean arterial pressure (-10 +/- 14% and -6 +/- 12% for groups 1 and 2, respectively) but increased the heart rate (15 +/- 18% and 13 +/- 16, respectively). For continuous adenosine infusions, mean coronary flow velocity increased 64 +/- 104%, 122 +/- 94% and 198 +/- 59% and 15 +/- 51%, 110 +/- 95% and 109 +/- 86% in groups 1 and 2, respectively for each of the three doses. Mean coronary flow velocity increased significantly after 100 and 150 micrograms/kg of adenosine and 10 mg of intracoronary papaverine (48 +/- 25, 52 +/- 19 and 54 +/- 21 cm/s, respectively; all p less than 0.05 vs. baseline) and was significantly higher than in group 2 (37 +/- 24, 32 +/- 16, 41 +/- 23 cm/s; all p less than 0.05 vs. group 1). The coronary vasodilator reserve ratio (calculated as the ratio of hyperemic to basal mean flow velocity) for adenosine and papaverine was 2.94 +/- 1.50 and 2.94 +/- 1.00, respectively, in group 1 and was significantly and similarly reduced in group 2 (2.16 +/- 0.81 and 2.38 +/- 0.78, respectively; both p less than 0.05 vs. group 1). Low dose bolus injection of adenosine increased mean velocity equivalently to that after continuous infusion of 100 micrograms/kg, but less than after papaverine. There was a strong correlation between adenosine infusion and papaverine for both mean coronary flow velocity and coronary vasodilator reserve ratio (r2 = 0.871 and 0.325; SEE = 0.068 and 0.189, respectively; both p less than 0.0005). No patient had significant arrhythmias or prolongation of the corrected QT (QTc) interval with adenosine, but papaverine increased the QT (QTc) interval from 445 +/- 44 to 501 +/- 43 ms (p less than 0.001 vs. both maximal adenosine and baseline) and produced nonsustained ventricular tachycardia in one patient.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1869736 TI - Tolerance and safety of pharmacologic coronary vasodilation with adenosine in association with thallium-201 scintigraphy in patients with suspected coronary artery disease. AB - Adenosine thallium-201 myocardial scintigraphy is a promising test for coronary artery disease detection, but its safety has not been reported in large patient cohorts. Accordingly, the tolerance and safety profile of adenosine infusion were analyzed in 607 patients (351 men, 256 women, mean age 63 +/- 11 years) undergoing this test either because of suspected coronary artery disease (Group I, n = 482) or for risk stratification early (5.2 +/- 2.8 days) after myocardial infarction (Group II, n = 125). Adenosine increased the heart rate from 74.5 +/- 14.0 to 91.8 +/- 15.9 beats/min (p less than 0.001) and decreased systolic blood pressure from 137.8 +/- 26.8 to 120.7 +/- 26.1 mm Hg (p less than 0.001). Side effects were frequent and similar in both groups. Flushing occurred in 35%, chest pain in 34%, headache in 21% and dyspnea in 19% of patients. Only 35.6% of Group I patients with chest pain during adenosine infusion had concomitant transient perfusion abnormalities, compared with 60.7% of Group II patients (p less than 0.05). First- and second-degree AV block occurred in 9.6% and 3.6% of patients, respectively, and ischemic ST changes in 12.5% of cases. Concomitance of chest pain and ischemic ST depression was uncommon (6%) but, when present, predicted perfusion abnormalities in 73% of patients. Most side effects ceased rapidly after stopping the adenosine infusion. The side effects were severe in only 1.6% of patients and in only six patients (1%) was it necessary to discontinue the infusion. No serious adverse reactions such as acute myocardial infarction or death occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869737 TI - Quantitative thallium-201 single-photon emission computed tomography during maximal pharmacologic coronary vasodilation with adenosine for assessing coronary artery disease. AB - The diagnostic value of maximal pharmacologic coronary vasodilation with intravenously administered adenosine in conjunction with thallium-201 single photon emission computed tomography (SPECT) for detection of coronary artery disease was investigated in 101 consecutive patients who had concomitant coronary arteriography. Tomographic images were assessed visually and from computer quantified polar maps of the thallium-201 distribution. Significant coronary artery disease, defined as greater than 50% luminal diameter stenosis, was present in 70 patients. The sensitivity for detecting patients with coronary artery disease using quantitative analysis was 87% in the total group, 82% in patients without myocardial infarction and 96% in those with prior myocardial infarction; the specificity was 90%. The sensitivity for diagnosing coronary artery disease in patients without infarction with single-, double-and triple vessel disease was 76%, 86% and 90%, respectively. All individual stenoses were identified in 68% of patients with double-vessel disease and in 65% of those with triple-vessel disease. The extent of the perfusion defects, as quantified by polar maps, was directly related to the extent of coronary artery disease. In conclusion, quantitative thallium-201 SPECT during adenosine infusion has high sensitivity and specificity for diagnosing the presence of coronary artery disease, localizing the anatomic site of coronary stenosis and identifying the majority of affected vascular regions in patients with multivessel involvement. PMID- 1869738 TI - Echocardiographic demonstration of decreased left ventricular dimensions and vigorous myocardial contraction during syncope induced by head-up tilt. AB - Two-dimensional echocardiography was performed during a head-up tilt test in 11 control subjects (group I) and 18 patients with recurrent unexplained syncope. In four patients (group II), the head-up tilt test was negative at baseline and after isoproterenol infusion. Syncope was induced during baseline head-up tilt in nine patients (group III) and after isoproterenol challenge in five (group IV). The echocardiographic variables assessed were left ventricular end-systolic and end-diastolic areas and percent fractional shortening. At the end of head-up tilt, end-systolic area decreased by 4.5 +/- 1.3 and 3.0 +/- 1.2 cm2 in groups III and IV, respectively, compared with 0.5 +/- 0.7 and 0.2 +/- 0.1 cm2 in groups I and II, respectively (p less than 0.04). Similarly, end-diastolic area decreased by 5.5 +/- 2.6 cm2 in group III compared with 2.7 +/- 1.9 and 1.75 +/- 0.4 cm2 in group I and II, respectively (p less than 0.04). Additionally, at the end of the baseline study, fractional shortening was significantly greater in group III and group IV (43 +/- 5%) than in groups I and II (p less than 0.01). In conclusion, syncope induced by head-up tilt is associated with vigorous myocardial contraction and a significant decrease in left ventricular end systolic dimensions. This left ventricular hypercontractility may play an important role in the pathogenesis of syncope induced by head-up tilt. PMID- 1869739 TI - Importance of left ventricular systolic function in the assessment of left ventricular diastolic function with Doppler transmitral flow velocity recording. AB - To study the effect of left ventricular systolic function on the Doppler transmitral flow velocity pattern, Doppler echocardiographic variables were correlated with hemodynamic indexes in 11 control subjects and 58 patients with heart disease. All underwent cardiac catheterization performed with use of a Millar micromanometer. The time constant of left ventricular isovolumetric pressure decrease and left ventricular end-diastolic myocardial stiffness was calculated. The 58 patients were classified into two groups according to ejection fraction: group I (n = 30; ejection fraction greater than 55%) and group II (n = 28; ejection fraction less than 50%). Compared with the control subjects, patients in group I had impairment only of left ventricular relaxation (time constant 47 +/- 9 vs. 38 +/- 3 ms; p less than 0.01), whereas patients in group II had, in addition to impaired left ventricular relaxation (time constant 52 +/- 11 vs. 38 +/- 3 ms; p less than 0.01), increased preload, increased pulmonary capillary pressure (12 +/- 8 vs. 5 +/- 3 mm Hg; p less than 0.01) and increased myocardial stiffness (2,018 +/- 980 vs. 1,050 +/- 218 g/cm2; p less than 0.01). In group I, there was a significant partial correlation coefficient between the time constant and deceleration half-time (r = 0.54). In group II, a strong correlation existed between myocardial stiffness and peak atrial filling velocity (r = -0.71) and between myocardial stiffness and the ratio of peak atrial to peak rapid filling velocity (r = -0.71).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869740 TI - Effective aortic regurgitant orifice area: description of a method based on the conservation of mass. AB - The natural history of aortic regurgitation is incompletely understood in part because of the lack of a simple method to estimate the defect size. A method of determining the effective regurgitant orifice area that combines Doppler catheter and Doppler echocardiographic techniques and is based on the principle of conservation of mass (the continuity equation) is described. To validate the application of the Doppler catheter system for measuring regurgitant supravalvular diastolic flow, an in vitro model of retrograde aortic flow was used. These studies indicated that measurements of supravalvular retrograde velocity with the Doppler catheter accurately reflect retrograde diastolic velocity when the aorta is less than 4.8 cm in diameter. Twenty-three patients undergoing cardiac catheterization were studied; 20 of these patients had aortic regurgitation. Retrograde supravalvular diastolic velocity was determined from a Doppler catheter positioned above the aortic valve. The effective regurgitant orifice area was calculated with use of the Doppler catheter-derived regurgitant volume and mean transvalvular diastolic velocity as determined by either catheterization or continuous wave Doppler echocardiography. The catheterization derived regurgitant orifice area increased with the angiographic grade of as follows: 1+ (0.04 to 0.10 cm2), 2+ (0.15 to 0.49 cm2), 3+ (0.29 to 1.11 cm2) and 4+ (1.24 to 1.33 cm2). By combining Doppler catheter, echocardiographic and cardiac catheterization techniques, the effective aortic regurgitant orifice area may be estimated; this hydrodynamic area correlates with grading by supravalvular aortography. Calculation of this area provides a quantitative alternative to aortography for estimating the severity of aortic regurgitation but should be used with caution in patients with a markedly dilated aorta. PMID- 1869741 TI - Errors in pressure gradient measurement by continuous wave Doppler ultrasound: type, size and age effects in bioprosthetic aortic valves. AB - The accuracy of continuous wave Doppler ultrasound in deriving pressure gradients across bioprosthetic heart valves was evaluated in an in vitro pulse duplicator. Simultaneous pressure transducer and Doppler measurements were made in new and explanted aortic bioprosthetic valves of several sizes and four types: Carpentier Edwards, Ionescu-Shiley, Hancock standard and Hancock modified. The mean and peak gradients calculated by the modified Bernoulli equation from Doppler velocity measurements were always greater than those measured manometrically, despite corrections for location dependence of the manometric gradient (or pressure recovery). The relation between manometric and ultrasonically determined gradient was found to be statistically dependent on the valve type (mean gradient p less than 0.0001; peak gradient p = 0.0003) and size (mean gradient p = 0.0089; peak gradient p = 0.0107). Effects of implantation were observed, but were not shown to be significant. It is concluded that the continuous wave Doppler velocity data overestimated prosthetic valve pressure gradient in all cases, even when pressure recovery was taken into account. Clinicians should be wary of Doppler data when making major diagnostic or therapeutic decisions. PMID- 1869742 TI - Electrophysiologic studies during acute myocardial infarction: do they prognosticate? PMID- 1869743 TI - Time-dependent variation in the cardiac conduction system assessed in young healthy individuals at weeks' interval: implications for clinical trials. AB - The time-dependent physiologic variations of the cardiac conduction system were evaluated at repeated invasive studies in 10 healthy individuals. Their mean age was 28 years (range 22 to 34) and they volunteered to undergo two electrophysiologic studies at intervals of 14 to 63 days (mean 25). The coefficients of variation, repeatability and reproducibility, which should be the preferred statistics when assessing the reproducibility of continuous variables, were calculated. The mean sinus cycle length had a high reproducibility, with coefficients of variation between 2% and 6%. The mean and maximal sinus node recovery times, however, varied considerably. The reproducibility was very high for ventricular depolarization and repolarization (QRS, JT, QT), with coefficients of variation between 2% and 6%. The coefficients of variation were below the acceptable 10% value for intraatrial conduction, atrioventricular (AV) node conduction, His-Purkinje conduction as well as the Wenckebach point; for the effective refractory period of the AV node, it was 12%. Repeat invasive electrophysiologic testing is a safe and reproducible method for evaluating and comparing cardioactive drug effects in healthy subjects. The same statistical analyses were applied to previously published studies on continuous electrophysiologic variables, which allowed comparisons among different groups of healthy and sick persons, as well as among different electrophysiologic variables and procedures. Furthermore, the minimal actual treatment differences that can be detected with a reasonable (80%) probability at a predetermined (5%) significance level using a crossover design were estimated for different electrophysiologic variables. These data will assist in the calculation of the necessary sample size for clinical trials and related purposes. PMID- 1869744 TI - Morphologic comparison of frequency and types of acute lesions in the major epicardial coronary arteries in unstable angina pectoris, sudden coronary death and acute myocardial infarction. AB - The frequency and type of acute lesions in the four major (right, left main, left anterior descending, left circumflex) epicardial coronary arteries were examined at necropsy in 14 patients with unstable angina pectoris, 21 patients with sudden coronary death and 32 patients with a fatal first acute myocardial infarction. None of the 67 patients had a grossly visible left ventricular scar (healed myocardial infarct) and only the group with acute myocardial infarction had left ventricular myocardial necrosis. Although the frequency of intraluminal thrombus was similar in patients with unstable angina (29%) and sudden death (29%) and significantly lower than in those with acute infarction (69%) (p = 0.02), the thrombus in the patients with unstable angina and sudden death consisted almost entirely of platelets and was nonocclusive, whereas the thrombus in the group with acute infarction consisted almost entirely of fibrin and was occlusive. The frequency of plaque rupture was insignificantly different in the groups with unstable angina (36%) and sudden death (19%), and was significantly lower than in the group with acute infarction (75%) (p = 0.02). The frequency of plaque hemorrhage was insignificantly different in the groups with unstable angina (64%) and sudden death (38%) and was significantly lower than in the group with acute infarction (90%) (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869745 TI - A new method for noninvasive estimation of ventricular septal defect shunt flow by Doppler color flow mapping: imaging of the laminar flow convergence region on the left septal surface. AB - An accurate but simple and noninvasive method for quantifying flow across a ventricular septal defect has yet to be implemented for routine clinical use. A region of flow convergence is commonly imaged by Doppler color flow mapping on the left septal surface of the ventricular septal defect, appearing as a narrowed region of laminar flow with aliased flow velocities entering the orifice. If the first aliasing region represents a hemispheric isovelocity boundary of a surface of flow convergence and all flow at this surface crosses the ventricular septal defect, the flow through the defect can be estimated by using the radius (R), measured from the first alias to the orifice, and the Nyquist limit (NL) velocity (the flow velocity at the first alias). Doppler color flow imaging was performed in 18 children with a single membranous ventricular septal defect undergoing cardiac catheterization at a mean age of 29.8 months (Group I). Indexes of maximal flow rate across the defect were developed from either the radius or the area, obtained by planimetry, of the first alias, based on Doppler color flow images. All indexes were corrected for body surface area and compared with shunt flow (Qp-Qs) and pulmonary to systemic flow ratio (Qp/Qs) determined at cardiac catheterization. Doppler color flow indexes derived from images of flow convergence in both the long-axis (n = 15) and oblique four-chamber (n = 10) views correlated closely with Qp/Qs (r = 0.71 to 0.92) and Qp - Qs (r = 0.69 to 0.97).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869746 TI - Doppler color mapping of the proximal flow convergence region: a new quantitative physiologic tool. PMID- 1869747 TI - A novel method to maintain ductus arteriosus patency. AB - Survival of patients with certain ductal-dependent congenital heart diseases depends on continued patency of the ductus arteriosus or the surgical creation of an aortopulmonary shunt. The latter may be difficult in the presence of hypoplastic pulmonary arteries. Long-term prostaglandin therapy may be used to maintain ductal patency but is not without limitation and side effects. This experimental study describes a novel approach to maintain ductal patency with a stainless steel stent. Six newborn lambs less than or equal to 48-h old had a ductal stent placed during right heart catheterization. Two lambs less than 36-h old had a stent delivered by the arterial route. The stent was delivered and released at the target with relative ease and no incidence of embolization. Continued ductal patency up to 3 months was demonstrated by repeat cardiac catheterization and angiography, two-dimensional color Doppler echocardiography and postmortem examination. The experimental model provides a left to right shunt model in which the size may be increased as the animal grows. More important, a ductal stent could be used to maintain ductal blood flow in neonates and infants with ductal-dependent cardiac malformations, thereby avoiding a thoracotomy. PMID- 1869748 TI - Diastolic mitral regurgitation with atrioventricular conduction abnormalities: relation of mitral flow velocity to transmitral pressure gradients in conscious dogs. AB - Diastolic mitral regurgitation is a common finding that can be detected with use of Doppler echocardiographic techniques in patients with atrioventricular (AV) conduction abnormalities. With use of simultaneous hemodynamic and Doppler techniques, mitral flow velocity, mitral valve motion and transmitral pressure gradient were studied during 50 cardiac cycles each of spontaneous or atrial paced first- and second-degree AV block in five lightly sedated dogs. Diastolic mitral regurgitation was detected during atrial relaxation on all beats in which ventricular contraction was delayed greater than 190 ms. In all dogs the diastolic regurgitation was associated with a reverse transmitral pressure gradient (3.7 +/- 1.1 mm Hg in first-degree AV block and 3.2 +/- 1.5 mm Hg in second-degree AV block) that occurred primarily as the result of a decrease in atrial pressure with atrial relaxation. These reverse pressure gradients were as large as the maximal forward transmitral gradients in early diastole (2.9 +/- 0.9 mm Hg in first-degree AV block and 3.1 +/- 0.7 mm Hg in second-degree AV block) and larger than the maximal forward pressure gradients at atrial contraction (1.7 +/- 0.5 and 1.4 +/- 0.6 mm Hg, respectively, p less than 0.05). The maximal reverse pressure gradient during atrial relaxation was also as large as the reverse pressure gradient in mid-diastole (2.7 +/- 0.9 and 2.8 +/- 1.0 mm Hg, respectively), associated with deceleration of early diastolic mitral flow. Peak diastolic mitral regurgitation velocity coincided with the maximal reverse transmitral gradient and was usually larger than anterograde mitral flow velocity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869749 TI - Dissociation of diastolic pressure-segment length and pressure-wall thickness relations during vasodilation in the conscious dog. AB - The effects of pharmacologic vasodilation and reductions in circumflex coronary artery pressure on the ventricular diastolic pressure-segment length and pressure wall thickness relations were studied in nine conscious dogs equipped with an inflatable cuff on the proximal circumflex artery, a micromanometer in the left ventricle and four sets of piezoelectric crystals to measure wall thickness and endocardial segment length in the left circumflex and left anterior descending artery territories. Adenosine infusion into the circumflex coronary artery increased endocardial and transmural blood flow to that territory (measured by microspheres) by 436% and 487%, respectively (both p less than 0.05), and shifted the left circumflex artery territory pressure-wall thickness curve upward (p less than 0.05) without affecting the circumflex pressure-segment length, the left anterior descending artery territory pressure-segment length or pressure-wall thickness curves significantly; papaverine also shifted the circumflex region pressure-wall thickness curve upward (p less than 0.05). Both with and without vasodilation, moderate reductions in circumflex artery perfusion pressure did not affect the position of the ventricular pressure-wall thickness or the pressure segment length curve (although during adenosine infusion endocardial blood flow decreased from 436% to approximately 100% of control values). More severe reductions in perfusion pressure (less than 45 mm Hg under control conditions and less than 30 mm Hg during adenosine infusion) decreased coronary blood flow below control values and caused a marked downward shift of the circumflex region pressure-segment length curve without affecting the position of the pressure-wall thickness curve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869750 TI - Effect of transient coronary occlusion on coronary blood flow autoregulation, vasodilator reserve and response to adenosine in the dog. AB - Myocardial ischemia of short duration (15 to 20 min) produces myocardial "stunning" during reperfusion. The vasoregulatory and contractile status of reperfused myocardium during normal and reduced perfusion pressures is of interest in the treatment of patients with unstable angina. In the present study the effects of 15 min of reversible ischemic injury on several aspects of coronary vasoregulation were assessed with use of pressure-flow curves in anesthetized open chest dogs. The left anterior descending coronary artery was cannulated and perfused with arterial blood with use of a servo-controlled roller pump. The autoregulatory gain and an adenosine dose-response curve for coronary flow before and after ischemia and reperfusion were obtained. The maximal autoregulatory gain values in the pressure range of 140 to 60 mm Hg were not significantly different before and after ischemia and reperfusion (0.41 +/- 0.08 vs. 0.5 +/- 0.06, p greater than 0.1). The adenosine dose-response curve was significantly shifted to the right after reperfusion; however, coronary blood flows during maximal adenosine vasodilation over a large range of perfusion pressures (140 to 60 mm Hg) were significantly greater after ischemia and reperfusion. The pressure-dependent decrease in segment shortening (sonomicrometry) over the coronary pressure range of 160 to 30 mm Hg was similar in myocardium before and after stunning. Contractile function in the stunned myocardium at normal (100 mm Hg) and low (40 mm Hg) coronary perfusion pressures was similarly and significantly enhanced by the administration of adenosine. It is concluded that 1) coronary autoregulation is unchanged after brief ischemia and reperfusion; 2) although maximal coronary vascular conductance assessed with adenosine is greater after ischemia, the coronary circulation shows a decreased coronary sensitivity to exogenous adenosine; 3) the relation of contractile function to coronary pressure before and after stunning is unchanged; and 4) enhancement of function in stunned myocardium by vasodilation with adenosine occurs at low and normal perfusion pressures. PMID- 1869752 TI - Experimental infarct size reduction with calcium channel blockers. PMID- 1869751 TI - Effect of intracoronary diltiazem on infarct size and regional myocardial function in the ischemic reperfused canine heart. AB - This study was designed to investigate whether intracoronary diltiazem given before reperfusion could enhance myocardial salvage in the canine heart. Twenty five dogs were subjected to 90 min of coronary occlusion followed by 4 h of reperfusion. The dogs were assigned to one of three experimental groups. The early diltiazem group received intracoronary diltiazem into the distal coronary bed at the onset of coronary occlusion and for 60 min after reperfusion. The late diltiazem group received the same amount of drug beginning 15 min before reperfusion and the control group received saline solution for 90 min of occlusion and 60 min of reperfusion. Infarct size expressed as a percent of the area at risk was significantly smaller in the early and late diltiazem groups (15.6 +/- 3.6% and 21.2 +/- 5.1%, respectively) than in the control group (49 +/- 4.6%) (p less than 0.05). Intracoronary diltiazem restored systolic function of the stunned, previously ischemic tissue to essentially normal preocclusion values. Segmental shortening after reperfusion averaged 21.6% in the early diltiazem group versus 0 +/- 1.7% and 7.3 +/- 4% for the control and late diltiazem groups, respectively (p less than 0.05). Low dose intracoronary diltiazem did not alter hemodynamic variables or myocardial blood flow but did improve segmental shortening 2 and 6 h after reperfusion. These data indicate that intracoronary diltiazem given during occlusion or just before reperfusion increases the salvage of myocardium compared with the salvage achieved by reperfusion alone. These results also suggest that intracoronary diltiazem given during the ischemic period enhances systolic contractile function of postischemic stunned myocardium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869753 TI - Effect of coronary reocclusion after initial reperfusion on ventricular function and infarct size. AB - Reocclusion of a coronary artery after thrombolytic therapy occurs in approximately 12% to 33% of patients; however, there are few experimental data concerning reocclusion. Accordingly, to compare the effects of reocclusion versus sustained occlusion on the myocardium, a canine model (n = 12) of 2 h of left circumflex artery occlusion, 1 h of reperfusion and 1 h of reocclusion was studied. In a control group (n = 11), 3 h of circumflex artery occlusion was followed by 1 h of reperfusion. As a result, both groups had the same total duration of ischemia (3 h) and reperfusion (1 h). Hemodynamic measurements, radioactive microsphere injections and two-dimensional echocardiography were performed at baseline, occlusion and reperfusion for both groups and at the end of reocclusion for the experimental group. In vivo risk area was determined with Evans blue dye and infarct size with triphenyltetrazolium staining methods. Similar decreases in myocardial blood flow after coronary occlusion and similar reperfusion blood flows occurred in both groups. Despite intervening reperfusion in the reocclusion group, no significant difference was found in the infarct size/risk area ratio between the reocclusion and control groups (54.5 +/- 6.9% vs. 48.4 +/- 5.1%, respectively, p = NS). Two-dimensional echocardiography demonstrated a similar degree and extent (159 +/- 9 degrees vs. 153 +/- 12 degrees, p = NS) of left ventricular dysfunction with both the occlusion and reocclusion. In addition, there were no significant differences in global or regional left ventricular function between the two groups. However, reocclusion after reperfusion did produce a further deterioration in ischemic zone wall thickening (9.5 +/- 2.0% to 0.7 +/- 1.8%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869754 TI - Functional longitudinal dissociation versus decremental conduction in accessory pathways. PMID- 1869755 TI - Women's changing work roles: implications for the progress of the dietetic profession. PMID- 1869756 TI - Selected body composition and growth measures of junior elite gymnasts. AB - Selected body composition measures of female junior elite gymnasts (n = 146) were evaluated cross-sectionally (ie, we observed a younger and an older group at one point in time, not the same individuals over time). For certain comparisons, the gymnasts were grouped into a younger group (7- to 10-year-olds) and an older group (11- to 14-year-olds). Gymnasts were in the 50th percentile for weight:height ratio, regardless of age. However, weight:age and height:age percentiles progressively dropped from the 48th to the 20th as age increased. Body fat percentage did not differ significantly between age groups. Triceps and subscapular skinfolds were 63% and 56%, respectively, of the age-related standard for the younger group and 52% and 39%, respectively, of the age-related standard for the older group. Arm muscle circumference and calculated arm muscle area of the gymnasts were in about the 75th percentile, regardless of age grouping. In general, as they grew older, gymnasts became progressively smaller in weight and height for age but were highly muscled for size. The steady age-related drop in height:age and weight:age percentile may be attributable to nutritional deficits, a sport-specific selection favoring retention of small but powerful gymnasts, or a combination of these factors. We recommend that young gymnasts be carefully observed longitudinally by trained nutrition professionals to ensure that inadequate nutrient intake is not a contributing factor to poor growth or health. PMID- 1869757 TI - Pica practices of pregnant women. AB - This report summarizes current knowledge about pica practices during pregnancy through a systematic review of the literature for the period 1950 through 1990. Pica behavior was considered in terms of its prevalence, risk factors, clinical profile, and effect on pregnancy outcome. Data on pica practices by pregnant women are limited and inconclusive but reveal several interesting relationships. The prevalence of pica among pregnant women in high-risk groups declined between the 1950s and the 1970s but now remains steady, affecting about one fifth of high risk women. Women at high risk of pica are more likely to be black, to live in rural areas, and to have a positive childhood and family history of pica. The clinical picture of the disorder during pregnancy is not well described. The evidence suggests that pica during pregnancy results in anemia, but it is not definitive. Pica also has been associated with maternal and perinatal mortality. We conclude that the behavior is more prevalent than commonly believed, shows no sign of further decline, and may have serious effects, particularly anemia, on mother and infant. Dietetic practitioners who counsel pregnant women should ask questions about pica when they conduct nutrition assessments of their clients. PMID- 1869758 TI - Correlates of breast-feeding in a low-income population of whites, blacks, and southeast Asians. AB - Infant feeding was examined in 492 children in a population-based survey conducted in a low-income, urban county of St Paul, Minn. Of 41 Southeast Asian infants who were foreign born, 93% (38) had been breast-fed compared with 10% (12) of Southeast Asian infants born in the United States (n = 116). Among non Southeast Asian infants, 73% (173) of whites (n = 237), 63% (27) of blacks (n = 43) and 65% (36) of other ethnic groups (n = 55) had been breast-fed. Among the non-Southeast Asian infants, the initiation of breast-feeding was associated with higher parental education and with being married. Ethnic group, level of poverty, and participation in the Supplemental Food Program for Women, Infants, and Children during pregnancy did not appear to influence the initiation of breast feeding. The findings indicate a higher incidence of breast-feeding than in previous surveys of low-income black and white women; however, this may reflect the higher educational level of the non-Southeast Asian study population. In contrast, the sharp decline in the incidence of breast-feeding among Southeast Asian infants who were born in the United States compared with those who were foreign born indicates the need for public health approaches to strengthen traditional breast-feeding practices. PMID- 1869759 TI - Use of modified diets in nursing homes. AB - Randomly chosen medical charts of 212 elderly subjects in 11 nursing homes were reviewed to determine which characteristics of the subjects were most closely associated with their diet prescriptions. The chart reviews indicated that 104 (49.0%) of the 212 subjects had some type of nutrient-modified diet prescription. Eight patients who were tube fed were not included in subsequent analyses. Sodium restriction was the most common modification (60 [29.4%] of the remaining 204 patients) and calorie-controlled diets were also common (52 [25.5%] of the patients). Of the 55 patients with hypertension, 31 (56.4%) had no sodium restriction. Only 10% of all low-sodium diets limited sodium to 2 g per day. Of the 38 patients with diabetes, 7 (18.4%) had no prescription for calorie control, and there was no indication that increased dietary fiber was encouraged for diabetic patients. Only one of the 121 subjects with a diagnosis of coronary heart disease or atherosclerosis had a prescription for a cholesterol-lowering diet. Characteristics of the subjects not specifically related to diet or diagnosis, such as age, sex, duration of stay, and level of care, had no significant relationship to diet prescription. These findings suggest that the practitioners in our sample were not convinced of the efficacy of modified diets to control disease for most nursing home residents. PMID- 1869760 TI - Time spent in state-recommended functions by consultant dietitians in Wisconsin skilled nursing facilities. AB - In this study we determined how consultant dietitians working in Wisconsin skilled nursing facilities distributed their time among contracted duties. At the time of the study, the 400 skilled nursing facilities in Wisconsin employed 160 consultant dietitians. Of these, 135 consultant dietitians were eligible to participate in the study. A mailed questionnaire was used to collect data on educational background, experience, and actual time spent in state-recommended functions, additional resident-care functions, and additional non-resident-care functions. Completed, usable questionnaires were returned by 65 (48%) of the 135 consultant dietitians. Data were analyzed statistically and presented as medians, means, and standard deviations. Mean time (minutes) consultant dietitians spent per resident admission activity was as follows: data collection, 31.3; care planning, 28.9; resident counseling, 18.5; medical record review, 17.7; discharge referral, 15.4. Mean time (minutes) consultant dietitians spent per month in other activities was as follows: facility evaluation, 75.3; student training, 120; allied staff training, 38.7; foodservice staff training, 46.8; technician training, 128; menu planning, 76.9; diet manual review, 21.6; quality assurance programs, 31.8; quality assurance audits, 34; report preparation for facility administrator, 33.4; and policy development, 32.8. Mean times reported in this study may be used as time guidelines by the state of Wisconsin for evaluating how skilled nursing facilities contract for services of consultant dietitians. Other state and federal regulatory agencies could use the time guidelines for comparison and verification until future studies provide more data on time standards for state-recommended functions, additional resident-care functions, and additional non-resident-care functions. PMID- 1869761 TI - Family-oriented nutrition intervention for a lipid clinic population. AB - We have developed a unique, family-oriented approach to lowering plasma cholesterol concentrations in persons with familial hyperlipidemias. The approach includes individual clinic visits and group nutrition classes and uses dietary goals outlined in The New American Diet. A series of 13 nutrition classes is presented to small groups, usually composed of relatives from pedigrees with familial hypercholesterolemia or other familial hyperlipidemias. Dietary action goals, cooking demonstrations, food tasting, and finger-stick plasma cholesterol determinations are important components of the classes. Problem-solving discussion is encouraged in the group. Over the past 4 years, 143 hyperlipidemic individuals, along with at least 94 unaffected family members, have participated in 31 groups, which have met for at least six classes. Many clinic participants lower plasma cholesterol by 20% or more. Keys to the success of this program include emphasizing dietary therapy, using the family setting for nutrition intervention, providing hands-on experience with food and recipes, promoting problem solving for dietary action goals, measuring blood cholesterol during classes, and encouraging long-term follow-up for participants with physicians and dietitians. PMID- 1869762 TI - Drug-mineral interactions: a new responsibility for the hospital dietitian. AB - Recent hospital accreditation guidelines encourage hospital dietitians to monitor patient drug therapy and provide education regarding drug-food interactions. However, information concerning these interactions is lacking, even though they can occur frequently. Minerals in foods can complex with drugs and/or alter the gastrointestinal environment to affect the normal absorption processes of drugs and minerals. There are three types of drug-mineral interactions: (a) malabsorption of the mineral and/or drug; (b) mineral depletion and retention; and (c) drug-mineral interactions induced by simultaneous antacid ingestion. It is recommended that oral drugs be administered on an empty stomach 1 hour before or 2 hours after a meal and at least 2 hours before or after antacid use. A small snack of refined carbohydrates with low nutrient density can be consumed with drugs that cause gastric upset when given on an empty stomach. PMID- 1869763 TI - Nutrition components and assessment procedures of a university employee wellness program: a case study. AB - This article describes the various nutrition components and data collection tools developed and implemented within the Montana State University Employee Wellness Program. Nutrition components included a variety of classes, seminars, follow-up support groups, and individual consultations. Tools included surveys and computerized data input cards. It is important for dietetic professionals to initiate the development and implementation of a quality nutrition component within university employee wellness programs. PMID- 1869764 TI - Children in foster care: are they at nutritional risk? PMID- 1869765 TI - A clinical nutrition incentive program for dietetic technicians. PMID- 1869766 TI - Perspectives on nutrition during pregnancy: Part I, Weight gain; Part II, Nutrient supplements. PMID- 1869767 TI - Capsaicin and primary afferent neurons: from basic science to human therapy? PMID- 1869768 TI - Reflex changes in thermogenesis in the interscapular brown adipose tissue in response to thermal stimulation of the skin via sympathetic efferent nerves in anesthetized rats. AB - Reflex responses of both temperature in the interscapular brown adipose tissue (IBAT) and activity of the sympathetic efferent nerves innervating the IBAT to cutaneous thermal stimulation were examined in anesthetized rats. Thermal stimulation of the ear at 4 degrees C for 20 s produced a transient decrease in the temperature of the IBAT during this period, followed by a prolonged increase (lasting 7 min). This response was completely abolished in animals whose IBAT sympathetic nerves were bilaterally sectioned. Direct recording of IBAT sympathetic efferent activity revealed that thermal stimulation of the ear at 4 degrees C for 20 s increased activity for 80 s after the onset of stimulation. The threshold temperature of the cold stimulation for eliciting increased nerve activity was around 22 degrees C. However, warm stimulation up to 49 degrees C had no significant effect on activity. In addition to stimulation of the ear, cold stimulation of the face and neck at 4 degrees C also increased nerve activity, while warm stimulation at 49 degrees C of any skin area had no influence. The present results demonstrate that excitation of cutaneous cold receptors, but not warm or heat receptors, reflexly increases thermogenesis in the IBAT via excitation of sympathetic nerve activity, and that cold receptor afferents to cranial and cervical segments effectively increase nerve activity in the IBAT. PMID- 1869770 TI - Distribution of splenic, mesenteric and renal neurons in sympathetic ganglia in rats. AB - The distribution of postganglionic neurons innervating the spleen, intestine and kidney in paravertebral and prevertebral sympathetic ganglia was studied in rats using retrograde transport of fluorescent dyes. Labelled cells were counted in the thoracolumbar chain ganglia T6-L4, splanchnic ganglia and the solar plexus (fusion of left and right coeliac ganglia and superior mesenteric ganglion). Most splenic neurons were located in the splanchnic ganglion (64%), mesenteric neurons in the solar plexus (96%) and renal neurons in the sympathetic chain ganglia (80%). These three groups of neurons were distributed in overlapping ganglia within the paravertebral chain. Innervation of the spleen and intestine from the chain ganglia was bilateral, whereas innervation of the kidney was almost entirely ipsilateral. In conclusion, the sympathetic postganglionic neurons controlling the spleen, intestine and kidney have their cell bodies in different ganglia. These three groups of neurons are candidates for innervation by different subgroups of preganglionic neurons. PMID- 1869769 TI - Sympathoadrenal excitation and inhibition by lower brainstem stimulation in cats. AB - Effects of stimulation of brainstem sites on hemodynamics and plasma catecholamine levels were assessed in cats under chloralose-urethane anesthesia. Pressor areas of the dorsal medulla (DM) and ventrolateral medulla (VLM) and the depressor area of the paramedian reticular nucleus (PRN) were stimulated electrically using a monopolar electrode, or chemically using sodium glutamate microinjection. Plasma levels of norepinephrine (NE) and epinephrine (EPI) were measured in caval blood above the adrenal veins. Electrical stimulation of the DM and VLM produced increases in blood pressure and in plasma NE and EPI levels that were enhanced after acute vagotomies. The NE and EPI responses were attenuated after acute, bilateral adrenalectomies, confirming augmented adrenomedullary secretion, whereas the pressor responses were intact. Injection of sodium glutamate into the same pressor regions of the DM or VLM also produced pressor responses and elevated plasma catecholamine levels, indicating that the responses resulted from activation of neuronal perikarya. Stimulation of the PRN attenuated pressor and catecholamine responses during stimulation of the DM and VLM. The results indicate that pressor responses during stimulation of the DM and VLM are due at least partly to activation of perikarya in these regions, are associated with but not dependent on adrenomedullary activation, and are enhanced after vagotomy; and that neurons of the PRN exert inhibitory modulation of the pressor and adrenomedullary responses during stimulation of VLM and DM. PMID- 1869772 TI - Responses of rostroventrolateral medulla spinal vasomotor neurones to chemoreceptor stimulation in rats. AB - The activity of spinal projecting 'vasomotor' neurones of the rostroventrolateral medulla (RVL) has been recorded in anaesthetised and paralysed rats. They responded to carotid body chemoreceptor stimulation (0.208 M NaH2PO4) with an increase in discharge that preceded an evoked increase in arterial blood pressure. This initial excitatory response was followed by a fall in discharge correlated to the rise in blood pressure. RVL neurones, which had equivalent sensitivity to baroreceptor inputs but no spinal projecting axons, failed to exhibit the initial excitatory response on chemoreceptor stimulation. These observations suggest that the pressor response to chemoreceptor stimulation is mediated, at least partially, by excitation of RVL-spinal 'vasomotor' neurones. PMID- 1869771 TI - Cardiovascular changes in response to uterine stimulation. AB - These experiments examined cardiovascular responses to uterine horn distension in anesthetized rats. Changes in blood pressure and heart rate following distension of the uterine horn were compared in estrous and diestrous rats. In the estrous rats, there was a significant decrease in both heart rate and blood pressure following uterine horn pressure of 150 mmHg or greater. This depressor and bradycardia response did not reliably occur in the diestrous rats. To determine the afferent limb of this uterine-cardiovascular reflex, the pelvic and hypogastric nerves were cut consecutively and the effect of uterine horn distension was tested after each nerve cut. Following hypogastric, but not pelvic nerve transection, the cardiovascular responses to uterine horn distension were eliminated or severely attenuated. The importance of hypogastric afferent nerve fibers was further demonstrated by recording single unit activity in these fibers to uterine horn distension. The units responded with a pressure-dependent increase in firing rate, at uterine pressure levels of 50 mmHg and higher. To determine the efferent limb of the reflex, the cardiovascular responses were measured before and after vagus nerve transection. Elimination of this parasympathetic neural activity did not affect the inhibitory cardiovascular responses to uterine horn distension, suggesting that these fibers may not be responsible for the decrease in heart rate and blood pressure. Recordings of multi-unit activity from sympathetic efferent fibers in the renal nerve, a vasoconstrictor nerve, showed a decrease to uterine horn distension. A decrease in renal nerve efferent activity was observed at uterine horn pressures of 150 mmHg or greater and the time course of the renal nerve response paralleled the cardiovascular response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869773 TI - Reticulospinal vasomotor neurones in decerebrate rats: effect of pentobarbitone. AB - The pattern of discharge of rostroventrolateral 'vasomotor' neurones has been studied in the decerebrate rat before and following the administration of pentobarbitone. Baroreflex inputs were effective in both situations, but the sensitivity of the reflex was heightened in the anaesthetised decerebrate condition even though the anaesthetic depressed neuronal discharge. The application of this anaesthetic failed to depress the inhibitory action of iontophoretically applied gamma-aminobutyric acid whose effectiveness was, if anything, enhanced. Arterial blood pressure was also reduced on the administration of the anaesthetic. These observations, taken together, suggest that the action of this, and potentially other anaesthetic agents, in lowering blood pressure may be mediated, in part, by the lowering of activity of these rostroventrolateral 'vasomotor' neurones. PMID- 1869774 TI - [Techniques, results and indications of embryonic reductions in multiple pregnancies. Review of the literature]. AB - The authors report, after a review of the literature, the evolution of ideas concerning first-trimester terminations in multiple pregnancies. Different techniques are performed including transabdominal approach or transvaginal approach at the mean gestational age of 9 or 11 weeks of amenorrhea. Analysis of obstetrical results obtained after these procedures (rates of early or late abortions, preterm labor or in utero growth retardation) shows a high rate of abortions and demonstrate also that reductions are unable to prevent premature births. Indications are discussed: concerning pregnancies of high order (four or more), most part of authors agree with the procedure and also when a triplet pregnancy occurs on a scarred or malformed uterus. Concerning triplet pregnancies, the procedure remains considered by some teams as an unethical approach of theses gestations, specially when considering the recent advances in perinatal medicine. In all cases, a clear and complete information about the risks of these procedures should be given to couples faced with multiple pregnancies. PMID- 1869775 TI - [Children of personalized anonymous oocyte donation. Psychologic aspects]. AB - The first children born as a result of oocyte donation are being subjected to a psychological study. Despite the small number of cases and the reservations required, it appears that the mother's denial of both infertility and filiation rupture is massive at the onset of pregnancy and subsequently persists. The harmonious psychological development of these children might be related to this denial. PMID- 1869776 TI - [Lipid composition of peritoneal and follicular ovulatory fluid from patients participating in an in vitro fertilization protocol]. AB - The aim of this work is to study and compare lipid composition of peritoneal and ovulatory follicular fluid of women. The studied patients are involved in a FIV protocol. We have studied 53 peritoneal fluids and 90 follicular fluids from 33 patients. On each sample the following parameters are estimated: cholesterol, triglycerides, phospholipids, non esterified fatty acids (A.G.N.E.), HDL and LDL cholesterol, HDL and LDL phospholipids. Lipid composition of follicular and peritoneal fluids differ from these of blood plasma. The two mediums studies show no differences with regard to their lipid composition. In both cholesterol is only found as HDL cholesterol. Cholesterol arising from spermatozoa membranes may be implicated in capacitation phenomenon. HDL Cholesterol, the only form found in the studied mediums, may act as a cholesterol acceptor. Theses two points partially explain the fact that follicular and peritoneal fluids are good mediums for capacitation and survival of spermatozoa. PMID- 1869777 TI - [Ultrasonic prenatal diagnosis of lip and palate cleft. Report of 10 cases]. AB - Hare-lips and cleft palates are the most frequent manifestations of facial malformations (approximately 1 in 1,000 deliveries). The authors point out their technique for ultrasound assessment of the normal and pathological fetal face in the antenatal period. The antenatal examination gives an excellent diagnostic approach of the site and the nature and the extent of the abnormality. The screening for facial defects can be carried out routinely when studying the morphology in the second trimester of pregnancy or when there are other indications for doing this. Although the malformation is usually an isolated one, the management of these cases really depends mainly on any associated malformations than on the normality of the karyotype. PMID- 1869778 TI - [Prenatal diagnosis of abdomino-pelvic cystic lymphangioma as part of proteus syndrome]. AB - Proteus syndrome is difficult to diagnose owing to its low incidence and to the late recognition of its identity, due to polymorphous border diseases and to the polymorphous lesions which characterize. The authors report a prenatal diagnosis of abdominal and pelvic cystic lymphangioma as part of proteus syndrome. PMID- 1869779 TI - [Autoimmune thrombocytopenic purpura and pregnancy: significance of fetal blood punction]. AB - The authors report three cases of percutaneous fetal blood sampling at 38 weeks of pregnancies complicated by immunologic thrombocytopenia. In each case, the purity was perfect which is essential for using the examination with a view to the obstetrical management. The birth is programmed 24 or 48 hours later. In two cases, the neonatal control is in agree with the fetal blood sampling. In the third observation, the fetal platelet count in 142,000/mm3 and the newborn control 55,000/mm3: the only explanation is a very active process as usually state with newborns. There was no accident, and these samplings led to natural births. This approach seems to be the more effective for the evaluation of fetal platelet count and allow the choice of birth management. A cesarean section is decided in case of fetal thrombopenia lower than 50,000/mm3. PMID- 1869781 TI - [Course of metrorrhagia after biopsy curettage of the endometrium in women in reproductive age ]. AB - Authors working in the department of gynaecology and obstetrics in the university hospital of Caen with non-pregnant, non-menopausal women who were followed-up for at least 2 years after curettage have been able to carry out a retrospective study of 102 curettage and biopsies carried out either for diagnosis or to lessen bleeding in cases of metrorrhagia, menorrhagia or menometrorrhagia. Histology of the endometrium showed 40 cases of hyperplasia, 17 cases of polyps in the cavity of the uterus, 19 cases of atrophy, 6 cases of endometritis, 3 cases of atypical hyperplasia and 17 cases of normal endometrium. Hysterectomy was carried out in 22 cases because of recurrence of metrorrhagia. Anatomopathological examination of the operation specimens had shown iatrogenic atrophy of the mucosa in 13 cases (59%). The authors believe that this hypoplasia can be responsible for some recurrences and suggest that the state of the endometrium should be reassessed when metrorrhagia reappears in spite of well controlled treatment with progestagens. In the case of atrophy a cycle of oestrogens and progestagens should be started as it should be immediately after the curettage. The authors hope in this way to lessen the number of hysterectomies that have to be carried out because of failure of medical treatment. PMID- 1869780 TI - [Uterine metastasis of breast cancer. Report of 8 cases]. AB - The authors report a retrospective clinicopathologic study of 8 cases of uterine metastases from breast cancer. This is the largest surgical series dealing with this subject to be published to date. Not autopsy case has been considered. Much information has come out of this analysis and out of the international literature review: secondary location in the uterus can occur many years after the diagnosis and treatment of primary cancer of the breast; infiltration of the endometrium appears as common as infiltration of the myometrium; the histological type is nearly always invasive lobular carcinoma. The later was found in seven out of eight cases; the evaluation of hormone receptor levels in the surgical specimens has shown that most breast cancers metastasizing to the uterus are hormone dependent. PMID- 1869782 TI - [Risk factors of ectopic pregnancy. A case-control study at 7 maternity units in the Paris area]. AB - A case-control study was conducted in seven maternity hospitals in the Paris area in 1988 to evaluate the role of several risk factors in ectopic pregnancy (EP). A total of 279 cases and 307 controls were compared for sociodemographic characteristics, cigarette smoking, sexual reproductive and surgical histories and for the conditions under which conception occurred. Many factors were found to be associated with an increased risk of EP: cigarette smoking related to the number smoked at the time of conception (Odds Radio (OR) 1.26 to 2.72), appendicectomy (OR 1.25, 95% CI = 1.02-1.56), prior tubal surgery (OR = 2.42, 95% CI = 1.37-4.22), prior use of intrauterine devices (OR = 1.34, 95% CI = 1.02 1.80), induced ovulation cycle (OR = 1.66, 95% CI = 1.01-2.74) and prior EP (OR = 3.90, 95% CI = 2.27-6.75). Chlamydia trachomatis seropositivity was associated with an increased risk of EP (OR = 1.50, 95% CI = 1.04-2.13), but clinically reported pelvic inflammatory disease was not. Maternal age, parity, previous induced abortion and previous spontaneous abortion were not associated with EP. Use of an intrauterine device, progestagen micro-pill or the combined oestrogen/progestagen pill at the time of conception were associated with a lower risk of intrauterine pregnancy than of EP. These findings confirm the importance of several of the previously reported risk factors for EP; STD's, previous EP and cigarette smoking. They also identify new risk factors: appendicectomy, induced ovulation cycle, and showed that the combined oestrogen/progestagen pill does not prevent ectopic pregnancy as effectively as it prevents intrauterine pregnancy. PMID- 1869783 TI - [Functioning of implantable catheters of intraperitoneal chemotherapy]. AB - Intraperitoneal chemotherapy with a totally implantable catheter was performed in 42 patients with advanced ovarian cancer who received 178 courses of chemotherapy administered in 2 l of solution. Major complication was inflow obstruction due to fibrosis around the catheter observed in 10 patients, 23.8% of the cases. Other complications were: leakage 3 (7.1%), pain 3 (7.2%), infection 3 (7.1%) and rectal perforation 1 (2.4%). Overall, these complications occurred in 15 patients (35.7%) and were the cause of treatment interruption in 7 (16.7%). Outflow obstruction which occurred in 23 patients (54.8%), did not create discomfort and could not be considered as a complication. Despite the problems, intraperitoneal chemotherapy with a totally implantable catheter appeared feasible in at least 80% of the patients. PMID- 1869784 TI - [Results of intraperitoneal chemotherapy of ovarian cancer]. AB - We studied a series of 42 patients with advanced ovarian cancer who received intraperitoneal chemotherapy post second-look laparotomy. High-dose cisplatin (200 mg/m2) alone or in combination with cytarabine (2 g) achieved 47% response rate. Median overall survival from second-look laparotomy was 44 months with cisplatin (36 cases), 15 months with carboplatin (600 mg/m2, 5 cases) and not reached at 3 yrs with mitoxantrone (25 mg/m2, 8 cases). Median overall and progression-free survival from second-look laparotomy were 44 and 39 months respectively in complete responders (15 cases), 20 months and 9 months where residual tumor less than 2 cm (21 cases), 22 and 12 months where tumor greater than 2 cm (6 cases). There was a significant difference in survival (P = 0.01) and progression-free survival (P = 0.002) between complete responders and patients whose tumor was less than 2 cm. Toxicity was acceptable except for carboplatin with constant grade 4 leukocytes or platelets toxicity. It was not demonstrated that high-dose intraperitoneal chemotherapy given post second-look laparotomy will improve survival in advanced ovarian cancer. Further studies of polychemotherapy or early administration are needed. PMID- 1869785 TI - [Ovarian abscess. Report of 2 cases]. AB - Ovarian abscess is very rare and is usually a complication of acute purulent salpingitis. It can however rarely be isolated. Wilson and Black found 28 cases of 75,262 women who were admitted to the Department of Gynaecology and Obstetrics in Philadelphia between 1948 and 1963. There are only 120 cases in the literature. We report here two cases of abscess of the ovary which were operated in our department at an interval of one month. PMID- 1869786 TI - [The initiative for a risk-free motherhood: which perspectives?]. AB - The "Safe Motherhood Initiative" started off with a first conference held in Nairobi in February 1987. In 1989, several conferences were organised throughout the world which led to a new current of opinion in favour of maternal health improvement. Governments, decision markers and aid agencies have been called upon to support such Initiative. In this paper, we review the main characteristics of the Safe Motherhood Initiative and analyse two main constraints which were insufficiently discussed during the conferences. The first one is the need to increase the efficiency of the existing health system. The second one is the problem which arises from poor acceptability by the populations of certain health activities promoted by the Initiative. By giving various examples, we describe how these factors may restrict its expected results. Proposals are made to increase the efficacy of the programmes and of activities promoted by the Initiative and to ensure its mid-range continuation. The authors suggest that specific attention and more resources have to be given to achieving specific operational researches, by taking into account the health behaviour of the populations, the characteristics of the existing health services and the resources available. Such research will lead to improved maternal health activities. PMID- 1869787 TI - [Simple locomotion and during load carrying in pregnant women]. AB - There have been few studies of the way women walk in pregnancy, though some of the causes of low back ache of which they complain have only been partially worked out. This is why this study has been carried out on ten women between the third and eighth month of pregnancy. The speed at which they walk and the parameters of the gait as well as the localization of the centre of gravity when keeping upright have been measured in these pregnant women as well as in twenty control women of the same age. The results show that the speed at which they walk whether with or without carrying a weight usually is identical at the beginning and the end of pregnancy. When walking normally the size of the steps taken are no larger in pregnant women than in the control patients (p less than 0.05). Though the results are not statistically significant the rhythm of the steps is faster as well as their being a reduction in the length of the steps between the third and eighth month of pregnancy. When carrying a weight the length of the steps does not change greatly with pregnancy (p less than 0.05) and it would seem therefore to be a good way of assessing the changes that locomotion undergoes in pregnancy. The fact that women do not walk faster or slower can give evidence that they adapt to the change in posture that happens in pregnancy and they make the best possible biomechanical use of the parameters of walking in order to economise total energy output of the organism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869788 TI - [Leg amputation as a result of attempted voluntary abortion]. AB - The authors looked at the clinical situation and the possible pathogenicity which in this case was almost certainly traumatic. It would explain the total absence of one leg at the delivery of a baby who had no other psychomotor changes. They used this very exceptional case history of the loss of the lower limb after an attempt at terminating a pregnancy to study the matter from the French and foreign bibliography on the subject, which anyhow is very short. There was an attempt to terminate a pregnancy at an undisclosed duration of amenorrhoea (between 9 and 13 weeks) by suction evacuation followed by curettage. On the medico-legal side the authors analysed the reasons why there was no penal indictment brought at the same time as the civil action was brought prosecution, and also points out that the Conseil d'Etat decided, contrary to the Administrative Tribunal who were petitioned as to the responsibility for the serious handicap this child suffered to be established publically. They analysed the evolution of judicial and administrative jurisprudence on the matter of failure to terminate a pregnancy. The authors list other possibilities for traumatising a fetus in utero when the inside of the uterus is explored either when the pregnancy is a spontaneous pregnancy or an assisted reproductive pregnancy. The cases of pregnancy requiring a reduction in the number of embryos who will be born or the destruction of handicapped children whose legal status seems not only to be recognised at birth, but even in utero by the judges of the supreme administrative court. PMID- 1869789 TI - [Fast determination of pulmonary surfactant in amniotic fluid using fluorescent polarization (FLM test Abbott)]. AB - A study of 60 amniotic fluids obtained by amniocentesis shows that the measurement of total surfactant phospholipids by the TDX Fetal Lung Maturity assay makes it possible to predict accurately fetal lung maturity. A sensitivity of 100% is similar to that of other tests currently used but with a higher specificity (93% instead of 65% for the L/S ratio and 55% for the phosphatidylglycerol). The phospholipid/albumin ratio is carried out automatically by means of a fluorescence polarization method with the TDX Abbott apparatus. A cut off value of 50 mg/g should be considered as a good fetal lung maturity indicator. The population studied was composed of women with an arterial hypertension (n = 6), diabetes (n = 9) preterm premature rupture of the membranes (n = 8), gemellary pregnancy (n = 5) or with a risk of premature outcome (n = 10). In all cases delivery occurred within 24 hours after the amniocentesis. The average gestational age was 36 weeks. Seven newborns (11%) presented hyaline membrane disease. In conclusion, this simple and rapid test seems to be adequate to evaluate with accuracy the fetal lung maturity in abnormal pregnancies. It must however, be associated with the determination of phosphatidylglycerol, when the fluid is contaminated by blood or meconium. PMID- 1869790 TI - [Nasopharyngeal cancer and pregnancy. Review of the literature. Report of a case]. AB - We present a case of a rare condition of nasopharyngeal cancer and pregnancy occurring together. We review the unusual epidemiological, clinical and prognostic features of this type of cancer. Because of the immunological changes that occur in pregnancy and because of the potential oncogenic role of Epstein Barr virus we consider that pregnancy worsens the prognosis for nasopharyngeal cancer. After having pointed out the risks of radiotherapy and particularly of chemotherapy in pregnancy, we discuss the need to carry out a therapeutic abortion because of the effect that pregnancy will have if it is allowed to go on to term. PMID- 1869791 TI - [Umbilical and cerebral Doppler velocimetry hypertension in pregnancy]. AB - The authors carried out a combined study using Doppler Flow Studies of the umbilical and fetal anterior cerebral arteries in 26 pregnancies which were complicated by maternal hypertension. Using the ratio between the cerebral and the umbilical blood flow it may be possible to diagnose intra-uterine growth retardation more accurately than using classical measurements. An inversion of the ratio between the cerebral and the umbilical flows has a great prognostic value with a sensibility of 91.6%, a specificity of 87.5% and a positive predictive value of 84.6% with a negative predictive value of 93.13%. There may however quite often be a lengthy interval of time between the appearance of change in the ratio and the appearance of fetal distress, so that this sign can only be one indication for delivery of the fetus. PMID- 1869793 TI - [Adverse effects of nalbuphine administered during labor]. PMID- 1869792 TI - [Newborn bacterial infection caused by materno-fetal contamination. Retrospective epidemiologic study at a maternity unit]. AB - A retrospective epidemiological study of neonatal bacterial infection due to contamination from the mother was carried out in maternity unit. We analysed the results of taking bacterial swabs from the skin and GI tract in newborn children when there was a possibility, or even probability, from the criteria given that there would be infection. These results compare with different criteria. In 19 months there were 2,622 live born children; 40.6% of those had swabs taken; the infection rate was 0.61% of newborns, but 16% of the newborns, had asymptomatic colonisation by bacteria. The high risks of finding positive swabs as shown by increased infection rates by colonisation occurred where the mothers had high temperatures. Our results led us to change the criteria for antibiotic treatment immediately after birth, in newborn babies. PMID- 1869794 TI - [Vitamin K and newborn hemorrhage]. PMID- 1869795 TI - Lymphocytes in the intestine: role and distribution. AB - Once a pathogen penetrates the surface epithelium, the process of immune activation begins. The pathogen is transported across the intestinal epithelium by M cells and presented to the underlying lymphocytes in Peyer's patches by MHCII positive enterocytes. At the same time, intraepithelial lymphocytes are activated and secrete interferon tau which increases the ability of enterocytes to present antigen. Simultaneously, intraepithelial lymphocytes may also cytolyse pathogens. In Peyer's patches, T-lymphocytes in parafollicular areas interact with antigen presenting cells and antigenic peptides to become activated. B lymphocytes in follicular areas are also initially activated by the interaction of antigen and their surface Ig. B-lymphocyte activation is enhanced by helper T lymphocytes so that B-lymphocytes begin to proliferate in germinal centres. Most B-lymphocytes at this stage are surface IgA positive whether induced by T-switch cells or by isotype specific T-lymphocytes. At the same time activated T suppressor cells and contrasuppressors regulate the immune response to maintain it at an optim level. All these lymphocytes then leave Peyer's patches via blood vessels to mesenteric lymph nodes and the spleen where further cellular activation occurs. Thereafter, activated lymphocytes return to the intestine either directly or via the peripheral circulation. Those that reach the intestine directly, differentiate into effector cells and enter the lamina propria. In the lamina propria, plasma cells and cytotoxic T-lymphocytes destroy pathogens by secreting specific Ig and by cytotoxicity respectively. Activated helper T lymphocytes in the lamina propria probably help in local responses by acting on the few resting B-lymphocytes present there. T-suppressor lymphocytes enter the epithelium to become intraepithelial lymphocytes and regulate responses by suppressor and contrasuppressor activities. Intraepithelial lymphocytes are also cytotoxic for luminal pathogens. Activated lymphocytes which do not return to the intestine directly enter the thoracic duct and thereby the general circulation. In this way a local gut response is converted into a systemic one and memory lymphocytes are disseminated throughout the body. In addition, suppressor and contrasuppressor T-lymphocytes also become available for peripheral effects. Large number of these lymphocytes remain in circulation, while others return to the intestine to provide local protection. A schematic representation of thetraffic of lymphocytes is shown in Fig. 3. PMID- 1869797 TI - Prevalence of Clostridium difficile in hospitalised patients with acute diarrhoea in Calcutta. AB - During a 12-month period, Clostridium difficile was isolated from 38 (11.1%) of 341 hospitalised patients suffering from acute diarrhoea and from five (3%) of 172 patients as control who were admitted with illnesses other than diarrhoea. It was the sole bacterial pathogen in 31 cases. 87% of the isolates obtained from patients with diarrhoea produced neutralisable cytotoxin. None of these patients had any history of previous treatment using antibiotics. No age or gender specific high incidence was observed. Clinical presentation in these patients revealed no distinctive pattern. Both dysenteric and diarrhoeal presentations were found, the latter being more frequent. The results suggest that Clostridium difficile by itself may be a causal agent of acute diarrhoea. PMID- 1869796 TI - Study of Entamoeba histolytica isolates from Calcutta with special reference to their zymodeme, animal pathogenicity and erythrophagocytosis. AB - Entamoeba histolytica isolates, obtained mainly from asymptomatic human cyst passers, were tested for their in vitro erythrophagocytic activity and lesion forming ability in hamster liver. Simultaneous zymodeme typing of the isolates showed that, along with the pathogenic zymodemes, a number of isolates having nonpathogenic zymodemes also produced liver lesions in hamsters and engulfed higher numbers of RBCs. The observed positive correlation between the rate of erythrophagocytosis of an E. histolytica trophozoite and its degree of lesion producing capacity in hamster liver suggest that the erythrophagocytosis assay in conjunction with the hamster liver inoculation test, can be useful in the identification of virulent E. histolytica isolates. PMID- 1869798 TI - Enterotoxigenicity of human and animal isolates of Campylobacter jejuni in ligated rat ileal loops. AB - Human and animal isolates of Campylobacter jejuni were tested for enterotoxigenicity in ligated loop of Charles-Foster rats. Of 21 isolates, 13 were proved to be toxin-positive in the initial experiments. However, the remaining 8 required one to three passages through the rat ileal loop before showing the capacity to produce enterotoxin. All isolates caused fluid accumulation comparable with the amount produced by the standard toxigenic strain of Vibrio cholerae 01 1naba 569B. The isolates of C. jejuni from human and animal sources did not show any quantitative difference in their capacity to produce enterotoxin. PMID- 1869799 TI - Aeromonas-associated diarrhoea in north India. AB - The incidence of Aeromonas-associated diarrhoea in patients attending the hospital attached to the Dayanand Medical College, Ludhiana, India was investigated during May 1984-May 1987. Microbiological examination of single faecal samples from 2,661 patients showed the presence of various enteropathogens of which details of only Aeromonas isolations are given and discussed in the present article. A small control sample of 105 age-matched healthy volunteers were also examined. Only 55 patients (2.1% of all patients) showed Aeromonas spp. in their stool samples on culture. Aeromonas as a single pathogen was isolated from 37 patients and, from 18 patients it was mixed with other enteropathogens. Stools of healthy controls did not contain any pathogen. Seven of 25 isolates of A. caviae, all 18 isolates of A. sobria and all 7 isolates of A. hydrophilla were shown to be enterotoxigenic by rabbit ileal loop test. There was no immunological cross-reaction between Aeromonas enterotoxin and Escherichia coli labile toxin antiserum. The Aeromonas isolates were susceptible to most of the commonly used antimicrobial agents except ampicillin and cephalothin. PMID- 1869800 TI - Failure of aspirin in symptomatic treatment of acute diarrhoea. AB - Aspirin-mediated prostaglandin inhibition has been suggested in symptomatic relief of diarrhoea. The aim of the study was to evaluate in a controlled double blind trial if a short-term treatment with aspirin could limit the clinical course of acute diarrhoea in adults. Seventy patients attending the Department of Infectious Diseases, General Hospital of Malmo, Sweden, with acute diarrhoea due to different causal agents, received either 1500 mg aspirin per day (n = 33) or placebo (n = 37) for two days. No difference was observed in the duration of diarrhoea, frequency and consistency of stools during treatment or subjective general discomfort. The previously reported effect of aspirin on acute diarrhoea could not be confirmed in this clinical study. PMID- 1869801 TI - A randomised, double-blind clinical trial of a maltodextrin containing oral rehydration solution in acute infantile diarrhoea. AB - We compared the efficacy of a maltodextrin containing oral rehydration salts (ORS) solution with that of the WHO recommended glucose-ORS solution in a double blind randomized study of treating 69 children (33 in experimental group; 36 in control group) aged 4-36 months with acute diarrhoea causing mild to moderate dehydration. Both the groups of children were similar in initial clinical characteristics and received only ORS solutions. No significant differences in stool output (median 88.0, range 34-320 g/kg body wt. in experiment vs 75.0, 25 410 g/kg in control), intake of ORS solution (125.0, 58-360 ml/kg body wt. vs 154, 130-250 ml/kg), and duration of recovery from diarrhoea (2.0 d, range 1-6 vs 2.0 d, 1-9) were found between the groups. The haematocrit and serum electrolyte values in the two groups 24 hours after starting treatment were also similar. The results suggest that the ORS containing maltodextrin (50 g/l) in place of glucose has no advantage over WHO-ORS in correcting mild to moderate dehydration of children with acute diarrhoea. PMID- 1869802 TI - Record of clinicopathological conference of the International Centre for Diarrhoeal Disease Research, Bangladesh. A 30-year-old woman with fever, diarrhoea, and wasting. Case 1--1991. PMID- 1869804 TI - International health. PMID- 1869803 TI - Bibliography on diarrhoeal diseases. PMID- 1869805 TI - A historical perspective on international health. AB - Between about 1875 and the early twentieth century, most major disease pathogens were identified and their epidemiology clarified. The technical and material developments of the nineteenth century led to a form of practical internationalism that was expressed also in the health sector. The Pan American Health Organization was established in 1902 to coordinate health issues in the Western Hemisphere. The Health Office of the League of Nations, now little known, played an important role in the 1920s and 1930s, particularly in the control of epidemic diseases in Eastern Europe and later in nutrition. The general framework of the League Health Office became the basis of the World Health Organization, founded in 1946. Certain international agencies play a special role in health; of these, United Nations Children's Fund (UNICEF) and the World Bank have a worldwide role. The Institute of Nutrition of Central America and Panama (INCAP) and the International Centre for Diarrhoeal Diseases Research, Bangladesh (ICDDR,B) are examples of essentially regional organizations with considerable influence. Private voluntary organizations, missions, and foundations have also had a substantial effect on health in certain circumstances. PMID- 1869806 TI - National and international health agencies. Profile of key players. AB - The major players in international health and health policy have a tremendous potential to contribute to the wellbeing of humankind. Multilateral organizations, such as WHO, have universal areas of concern. The financial multilateral agencies play a key role in influencing development through the leverage of financial resources. Bilateral agencies of donor countries influence health policy direction by the magnitude of their financial resources. Private organizations, including universities, foundations, professional associations, nongovernmental organizations, and US industry, play an important role in identifying important policy issues through research, designing and developing appropriate technology, and acquiring the knowledge base necessary to form sound international health policy decisions. PMID- 1869808 TI - The role of clinical epidemiology in establishing essential national health research capabilities in developing countries. AB - Health research directly relevant to the needs of the people of developing countries is essential for equity in development as well as for improving health planning and management. the international Commission on Health Research for Development has stressed the need to strengthen the capacity of developing countries, no matter how poor, to carry out essential national health research (ENHR). Clinical epidemiologists in developing countries can significantly contribute to the manpower available for ENHR. They play a major role in the provision and practice of appropriate health care by contributing to the critical assessment of priority health problems and by carrying out scientific evaluation of new and conventional intervention tools. In clinical epidemiology units in developing countries, transdisciplinary collaboration with social scientists and health economics has enhanced the capacity to do research that would influence decision-making and health policy, even as links with ministries of health and other ENHR-committed networks are being strengthened. The potential for carrying out ENHR will be multiplied as national and regional training centers for clinical epidemiology in selected developing countries are established. PMID- 1869809 TI - Applications and transfer of technology to the nations of the South. Biotechnology and the control of childhood enteric infections. AB - The optimal use of biotechnology to address the health care needs of developing countries entails the formation of interdisciplinary working groups linking basic biomedical scientists with public health workers, epidemiologists, physicians, and social scientists. Their mission should be congruent with and guided by the public health goals and primary care program of the country or region. Moreover, their research and development activities should lead to products that address a specific need and which are evaluable, cost-effective, and readily transferred to the public health sector. With respect to the enteric infections of childhood, the essential components of an integrated control effort are a field site where infections of this kind are common and readily studied; a local public health laboratory where the performance of new products can be tested and where technology transfer can occur; a basic science laboratory where molecular pathogenicity studies lead to new diagnostic tests, vaccines, and drugs; and a production laboratory where these products can be refined and prepared in sufficient amounts for field testing. This strategy is now being evaluated for the control of infantile diarrhea through the combined use of epidemiologic investigations, DNA probe and amplification techniques, and molecular fingerprinting. Together, these methods are yielding new information about microbial reservoirs and transmission systems; in turn, this information should lead to highly focused public health interventions. PMID- 1869807 TI - Public and private donor financing for health in developing countries. AB - Among the many variables that influence the outcome of national health status in both developed and developing countries, the availability and efficiency of financing is critical. For 148 developing countries, annual public and private expenditures from domestic sources (1983) were estimated to be approximately $100 billion. For the United States alone, annual public and private costs for medical care are almost five times larger ($478 billion, 1988). In contrast to domestic expenditures, the total flow of donor assistance for health in 1986 was estimated to be $4 billion, approximately 5% of total current domestic expenditures by developing countries. Direct donor assistance for development purposes by the United States Government approximates 0.5% of the US federal budget (1988). Approximately 10% of all United States development assistance is allocated for health, nutrition, and population planning purposes. While the total health sector contribution is on the order of $500 million annually, the US contribution represents about 13% of health contributions by all external donors. In sub Saharan Africa, all donor health allocations only reach 3.4% of total development assistance. While available data suggest that private and voluntary organizations contribute approximately 20% of total global health assistance, data reporting methods from private agencies are not sufficiently specific to provide accurate global estimates. Clearly, developing countries as a whole are dependent on the efficient use of their own resources because external financing remains a small fraction of total domestic financing. Nevertheless, improvement in health sector performance often depends on the sharing of western experience and technology, services available through external donor cooperation. In this effort, the available supply of donor financing for health is not restricted entirely by donor policy, but also by the official demand for external financing as submitted by developing countries. In perspective, the supply of financing for health greatly exceeds the receipt of well-articulated and officially approved proposals from developing countries. The major constraints that produce this imbalance are unfamiliarity of ministries of health with potential donor sources; passive approaches to external financing; unfamiliarity with proposal preparation; increasing competition within developing countries by competing sectors, such as industry and agriculture; limited numbers of trained personnel; and absence of an international system which is able to support developing countries in mobilizing external financing. Tested solutions to these issues have been applied in one geographic region.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1869810 TI - Population growth. Implications and problems. AB - Population growth in the twentieth century is at its highest level in history, with the world's population now doubling in approximately 40 years. An unprecedented 90 million people are being added worldwide each year, with most of the growth taking place in the developing world. The implications of this rate of growth are discussed, as are some of the program efforts underway to decrease the rate of increase. PMID- 1869811 TI - Nutritional problems of developing countries. AB - The nutritional problems of developing countries are conditioned by poverty, near exclusive reliance on plant sources of nutrients, and high rates of infections. Common deficiency diseases include protein-energy malnutrition, nutritional anemias, vitamin A deficiency, iodine deficiency, and possibly others. Population subgroups at particularly high risk are the children and women of poor families. Control of these nutritional diseases requires systematic diagnosis of the existing situation and appropriate intervention strategies such as targeted food and specific micronutrient supplementation, food fortification, nutrition education, and reductions in infections as well as general improvements in economic conditions and social equity. PMID- 1869812 TI - Acute respiratory infections. AB - During the past decade, recognition of the significance of pneumonia for childhood mortality has greatly increased. Etiologic studies have clarified the role of Streptococcus pneumoniae and H. influenzae as the pathogens most responsible for childhood pneumonia in developing countries. Case management intervention strategies using community health workers to identify cases of pneumonia by counting respiratory rate and observing chest indrawing have been shown to reduce ARI-related mortality. Although research is underway to develop more effective vaccines against Streptococcus pneumoniae and non-type b H. influenzae, effective case management will remain the most realistic method of reducing mortality in the next decade. Important gaps remain in our understanding of the pathogenesis, etiology, and epidemiology of acute respiratory infections. Our understanding is complicated by the multiplicity of viral and bacterial agents and their interrelationships, by an abundance of interacting host risk factors, and by diverse social, cultural, and environmental factors. However, sufficient knowledge is available to support the implementation of the WHO case management intervention strategies, which will save the lives of the many children now dying because of pneumonia. PMID- 1869813 TI - The Nairobi STD program. An international partnership. AB - Since 1980, Canadian, Belgian, and American scientists have been working together with colleagues in Kenya to understand the epidemiology and biology of sexually transmitted diseases (STDs) in Africa. The rapid spread of human immunodeficiency virus has dramatically increased the importance of this information. Interventions to slow the spread of all STDs and to reduce their consequences are now our major priority. However, this will require continuing research, ongoing training of scientists, epidemiologists, and technologists, and increasing financial support from industrialized societies. PMID- 1869814 TI - Chemicals and environmentally caused diseases in developing countries. AB - This chapter discusses international aspects of diseases resulting from exposure to chemical pollutants in the environment, with an emphasis on developing countries. These countries share many of the same problems of air, water, and pesticide pollution that face the more industrialized countries. In developing countries, however, the problems are compounded by a number of unique situations, viz., economic priorities, high burden of infectious diseases, impoverishment, and absence of a regulatory framework for the disposal of toxic chemicals. This discussion emphasizes the importance of interactions among toxicants, malnutrition, and infectious diseases for both urban and rural populations insofar as these interactions contribute to disease. Toxicants not only produce disease directly but also exacerbate diseases with other causes. Specific examples from developing countries demonstrate how human health effects from exposures to environmental chemicals can be assessed. While they do not strictly fall under the rubric of "developing countries," the public health consequences of inadequate control of environmental pollution in the East European countries should demonstrate the magnitude of the problem, except that in developing countries the public health consequence of environmental chemicals will be aggravated by the widespread malnutrition and high prevalence of infectious diseases. Much needs to be done before we can adequately quantify the contribution of environmental chemicals to morbidity and mortality in developing countries with the level of sophistication now evident in the charting of infectious diseases in these countries. PMID- 1869815 TI - Travel medicine and travel clinics. AB - In response to the vast number of American travelers to the developing world, the discipline of Travel Medicine has become an emerging specialty. There are presently no formal Board or other requirements to practice Travel Medicine, but bona fide practitioners of this field, who also usually direct travel clinics, should at the least be well-trained and experienced in tropical medicine and medical aspects of travel, and have had considerable overseas work experience. The concept of travel medicine and the need for travel clinics operated by well qualified physicians are discussed. The areas of involvement of travel clinics in protecting the health of the traveler are described. PMID- 1869816 TI - How to set up your program in international health. AB - The foregoing delineation on the rationale, structure, and process for development of a program or institute in international health is not meant to be prescriptive. Flexibility, relevance, and sensitivity to the local context-the academic health center setting--are crucial, just as these characteristics are the hallmark of successful international projects. The present era offers significant challenges in improving the health and well-being of the world's population. Fortunately, there is an enlightened climate for the development of innovative and collaborative approaches to meet these challenges within a framework of social justice and overall human development. It is the unique and unparalleled opportunity for US academic health centers to work with international colleagues toward this goal. PMID- 1869817 TI - Alma Ata and health for all by the year 2000. The roles of academic institutions. AB - The title of this article raises a complex set of questions. To begin, what happened at Alma Ata and the goal that emanated from it-Health for All by the Year 2000--are themselves controversial matters. At least there are some who are strongly critical of those events and ideas. Even without linking academic institutions with Alma Ata and HFA/2000, a controversy is spawned when one asks about the roles of such institutions in dealing with societal problems--which problems should a university address, and how deeply does a university become engaged in them, particularly if it carries the university out of the cloister into the trenches of societal conflict? Linking academic institutions with Alma Ata and HFA/2000 deepens the controversy but also provides a framework for examining the basic principles on which each is based, and for testing those principles against the realities of real world problems of health development. This article draws on recent critical assessments of both sides of the equation: a recent Consultative Committee to the Director General of WHO that analyzes the successes and failures of PHC development to date, and lays out conditions for greater effectiveness in the future; and the Technical Discussions of WHO on the Roles of Universities in the Strategy for Health for All that review traditional and progressive arguments about the roles of universities in their societies, and how HFA can be seen as fitting into that debate. The thinking contained in these documents provides ample opportunity to examine whether or not academic institutions should have a role that relates to Alma Ata and Health for All, and, in the end, takes the position that, indeed, this is an appropriate role for those universities prepared to make the commitment. The point is also made that such involvement cannot be effective if the scale of the institutional commitment is marginal--it must be substantial and institution-wide. An example is given of the Aga Khan University in Karachi, Pakistan, an institution avowedly committed to a community orientation and to health services development. The Network of Community-Oriented Educational Institutions for Health Sciences can be considered a movement of educational institutions in this direction. It is functioning with considerable creative initiative in addressing issues having to do with problem based teaching methods, community orientation, and partnerships with governmental health services.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1869818 TI - International health. Beyond the year 2000. AB - The Global Health Care Revolution of the Century, which began officially at Alma Ata in 1978, will help to achieve the Health for All goal by the year 2000. What will the next century usher in? Some of our achievements to date are highlighted, and lessons learned and yet to be learned are emphasized. Reorientation in the world's thinking to achieve health beyond the year 2000 is examined. PMID- 1869819 TI - In vitro effect of transforming growth factor-beta on progression of HIV-1 infection in primary mononuclear phagocytes. AB - In vitro-differentiated monocytes can be infected with the monocytotropic isolate of HIV-1/ADA. The infection is characterized by formation of giant cells and production of virus that can be found in cell supernatants or cell-associated. In this study, we demonstrate that the above described parameters of infection can be enhanced by a factor present in acidified M phi supernatants, suggesting that it might be transforming growth factor beta-1 (TGF-beta 1). When recombinant or purified TGF-beta were examined, similar activities were detected. This effect apparently is not because of changes in the cellular phenotype that could favor infection. The effect of TGF-beta is exerted on cells once infection is established or on cells with active virus production. The activity can be also demonstrated using U-937 cells. PMID- 1869820 TI - Development of diabetogenic T cells from NOD/Lt marrow is blocked when an allo-H 2 haplotype is expressed on cells of hemopoietic origin, but not on thymic epithelium. AB - Diabetes is a T cell-mediated process in NOD/Lt mice, with a major genetically recessive component of susceptibility linked to homozygous expression of the unique H-2g7 MHC haplotype. Heterozygous expression of the H-2nb1 haplotype derived from the NON/Lt strain confers diabetes resistance both in (NOD x NON)F1 hybrids and in NOD mice congenic for the H-2nb1 haplotype. However, diabetes resistance is abrogated in F1 hybrids by NOD/Lt bone marrow reconstitution. To establish whether the generation of beta cell autoreactive T cells from NOD/Lt bone marrow-derived precursors required at least heterozygous expression of the H 2g7 haplotype on thymic epithelium, adolescent thymectomized (NOD x NON)F1 mice were implanted with neonatal NON/Lt thymus grafts before lethal radiation and reconstitution with NOD/Lt bone marrow. Peripheral T cells maturing through this ectopic thymic implant exclusively expressed the NOD H-2g7 haplotype and were tolerant to H-2nb1 skin grafts. Nevertheless, diabetes developed in 32% of the NON/Lt thymus-grafted chimeras vs 38% of the sham-thymectomized NOD bone marrow chimeras. Thus, homozygous expression of the diabetes-resistant H-2nb1 haplotype on thymic epithelium failed to block development of a diabetogenic T cell repertoire. To examine if expression of H-2nb1 on hemopoietically derived APC could alter the diabetogenic potential of NOD/Lt marrow, diabetes-resistant NOD.NON-H-2nb1 congenic mice were mated with NOD/Lt mice to produce NOD-H-2g7/H 2nb1 heterozygous recipients. These were lethally irradiated and reconstituted with either NOD/Lt marrow alone, NOD.H-2nb1 homozygous congenic marrow alone, or a 1:1 mixture of the two marrow populations. By 25 wk of age, all of the MHC heterozygous recipients of NOD.NON-H-2nb1 marrow remained diabetes-free whereas 75% of the MHC heterozygous recipients of NOD/Lt marrow developed diabetes. A striking decrease in diabetes was observed when T cell precursors derived from NOD/Lt marrow interacted with H-2nb1 gene products on hemopoietically derived APC, inasmuch as only 7% of the MHC heterozygous recipients reconstituted with a 1:1 mixture of NOD/Lt and NOD.NON-H-2nb1 marrow developed diabetes. Peripheral leukocytes in all reconstitution classes expressed the MHC phenotype(s) of the marrow donor(s). Skin grafting confirmed that all reconstitution classes of MHC heterozygous recipients were tolerant to the H-2nb1 haplotype.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1869821 TI - A tyrosine kinase physically associates with the beta-subunit of the human IL-2 receptor. AB - Cell surface expression of the high affinity IL-2R regulates, in part, the proliferative response occurring in Ag- or mitogen-activated T cells. The functional high affinity IL-2R is composed of at least two distinct ligand binding components, IL-2R alpha (Tac, p55) and IL-2R beta (p70/75). The IL-2R beta polypeptide appears to be essential for growth signal transduction, whereas the IL-2R alpha protein participates in the regulation of receptor affinity. We have prepared and characterized two mAb, DU-1 and DU-2, that specifically react with IL-2R beta. In vitro kinase assays performed with DU-2 immunoprecipitates, but not anti-IL-2R alpha or control antibody immunoprecipitates, have revealed co precipitation of a tyrosine kinase enzymatic activity that mediates phosphorylation of IL-2R beta. Because both IL-2R alpha and IL-2R beta lack tyrosine kinase enzymatic domains, these findings strongly suggest that noncovalent association of a tyrosine kinase with the high affinity IL-2R complex. Deletion mutants of the intracellular region of IL-2R beta, lacking either a previously described "critical domain" between amino acids 267 and 322 or the carboxyl-terminal 198 residues (IL-2R beta 88), lacked the ability to co precipitate this tyrosine kinase activity, as measured by phosphorylation of IL 2R beta in vitro. Both of these mutants also failed to transduce growth-promoting signals in response to IL-2 in vivo. Analysis of the IL-2R beta 88 mutant receptor suggested that a second protein kinase mediating phosphorylation on serine and threonine residues physically interacts with the carboxyl terminus of IL-2R beta. This kinase may be necessary but, alone, appears to be insufficient to support a full IL-2-induced proliferative response. These studies highlight the physical association of protein kinases with the cytoplasmic domain of IL-2R beta and their likely role in IL-2-induced growth signaling mediated through the multimeric high affinity IL-2R complex. PMID- 1869822 TI - Granulocyte-macrophage colony-stimulating factor promotes the proliferation of human alveolar macrophages in vitro. AB - The effects of granulocyte-macrophage (GM-CSF) or macrophage-CSF on in vitro proliferation of human alveolar macrophages (AM) were evaluated. AM of healthy volunteers incubated with recombinant human GM-CSF revealed incorporation of [3H]thymidine in vitro. The maximum incorporation was observed at 20 U/ml of GM CSF on day 3. The proportion of proliferating cells incubated with 20 U/ml of GM CSF from day 3 to day 4 was 8 to 11% of the total, whereas 3 to 5% of cells proliferated without GM-CSF. The number of cell nuclei increased 1.30- to 1.68 fold in the initial 7 days during incubation with 20 U/ml of GM-CSF, whereas there was a 1.07- to 1.13-fold increase without GM-CSF. Conditioned media obtained by the incubation with human lung tissue exhibited similar effects as recombinant human GM-CSF on macrophages. The effects were completely abrogated by antibody against human GM-CSF. Immunohistochemically, GM-CSF was detected in lung cells including AM, alveolar epithelium, alveolar interstitial cells, and endothelial cells. In contrast, recombinant macrophage-CSF did not induce the proliferation of human AM, although it has been known to promote the proliferation of murine AM. These observations suggest that GM-CSF plays an important role among the regulatory factors that locally support the population of AM in human lungs. PMID- 1869823 TI - Regulation of murine mononuclear phagocyte inflammatory products by macrophage colony-stimulating factor. Lack of IL-1 and prostaglandin E2 production and generation of a specific IL-1 inhibitor. AB - The influence of macrophage (M)-CSF on the production of inflammatory mediators has been examined in murine peritoneal macrophages. Cultures of macrophages treated with up to 30,000 U/ml of human rM-CSF or with 10,000 U/ml of L929 derived M-CSF did not reveal either PGE2, IL-1, or IL-6 secretion. In contrast, LPS, which served as a positive control, stimulated production of significant levels of PGE2, IL-1, and IL-6. Furthermore, Northern blot analysis of macrophage RNA revealed a strong induction of IL-1 alpha and IL-6 mRNA by LPS but not by M CSF. Conditioned medium from macrophage cultures treated with purified L929 or human rM-CSF in combination with LPS exhibited a significant reduction of IL-1 bioactivity as compared with an LPS challenge alone. To investigate the mechanism involved in this M-CSF-dependent reduction of IL-1 bioactivity, we measured IL-1 alpha gene expression. The addition of M-CSF to LPS-treated macrophages did not affect IL-1 alpha mRNA levels suggesting that M-CSF may regulate production of an IL-1 inhibitor. This hypothesis was shown to be valid because removal of IL-1 alpha from conditioned medium of LPS plus M-CSF-treated cells allowed the detection of a nondialyzable factor that blocked IL-1-dependent thymocyte proliferation. The inhibitor appeared to be specific because it did not inhibit IL-2 and TNF bioactivities. Furthermore, this IL-1 inhibitor, which binds to cells and not to IL-1, competed with the binding of radioactive IL-1 alpha or beta to EL-4.6.1 cells. The results demonstrate that M-CSF alone does not induce proinflammatory mediators and PGE2 as was previously published. The data also suggest that M-CSF may play a role in the down-regulation of inflammatory responses. PMID- 1869824 TI - Effect of natural polymorphism at residue 86 of the HLA-DR beta chain on peptide binding. AB - Class I and class II MHC glycoproteins are highly polymorphic molecules that bind antigenic peptides and present them on cell surfaces for recognition by T lymphocytes. Even though MHC polymorphism has long been known to affect both peptide binding and recognition by the TCR, the role of individual amino acids of MHC proteins in these interactions is poorly understood. To examine the effect of a small number of amino acid residues on T cell stimulation, B lymphoblastoid cell lines homozygous for the closely related DR1 subtypes, Dw1 and Dw20, and the DR4 subtypes, Dw4 and Dw14, were compared for their ability to present an immunogenic influenza hemagglutinin peptide (HA307-319) to an Ag-specific, DR1,4 restricted T cell clone. B cell lines expressing DR1 Dw20 and DR4 Dw14 presented HA307-319 much less efficiently than DR1 Dw1 and DR4 Dw4 and bound a biotinylated analogue of the same peptide less well. Analysis of DRB1 gene sequences suggested that polymorphism at residue 86 had a major effect on peptide binding. Differences in binding of a set of HA307-319 analogues biotinylated at each residue to cells expressing DR1 Dw1 and DR1 Dw20 suggested that the polymorphism affected the interactions of many peptide residues with the class II molecule. In inhibition assays, DR1 Dw1 and DR4 Dw4 were shown to differ from DR1 Dw20 and DR4 Dw14 in their length requirements for peptide binding. Using a larger panel of homozygous B cell lines expressing many class II haplotypes, a Ser-309 substituted HA307-319 analogue was shown to bind to most B cell lines expressing Val-86 containing alleles (including DR1 Dw20 and DR4 Dw14) but failed to bind most B cell lines expressing Gly-86 alleles (including DR1 Dw1 and DR4 Dw4). The results indicated that polymorphism at residue 86 influenced the specificity and affinity of peptide binding and affected the conformation of peptide-DR protein complexes without completely eliminating T cell recognition. PMID- 1869825 TI - Biosynthesis and partial amino acid sequence of the human NDA4 antigen. An activation antigen common to B and T cell lineages. AB - NDA4, a cell surface protein of molecular mass 46 kDa common to activated peripheral blood B and T cells, plays a unique role in the control of B and T cell maturation. NDA4 inhibits B and T cell activation, as mitogen-stimulated B and T cell blastogenic responses are decreased in the presence of mAb NDA4, the antibody recognizing NDA4. After mitogen-activation, however, the regulatory function of NDA4 changes. Addition of mAb NDA4 to cultures of Staphylococcus aureus Cowan strain A-activated B cells or alloreactive T cell clones stimulates their proliferation. NDA4 epitopes are conserved across primate species lines and are present on transformed cells of neuroectodermal origin. NDA4 is synthesized as a molecular mass 50 kDa precursor and is processed to a mature 46 kDa form within 30 min. The NDA4 Ag also exists as soluble forms of 40 and 42 kDa. The membrane and soluble forms of NDA4 have been purified to homogeneity and sequenced by N-terminal Edman degradation. PMID- 1869826 TI - Purification, biochemical composition, and biosynthesis of the Mo3 activation antigen expressed on the plasma membrane of human mononuclear phagocytes. AB - Mo3 is an activation Ag expressed on the surface of human mononuclear phagocytes stimulated in vitro or in vivo by various activating factors. Mo3 is obtained by immunoprecipitation with anti-Mo3 mAb from lysates of PMA-stimulated U-937 cells. The Ag is a heterogeneous glycoprotein with a molecular mass range of 42 to 66 kDa (nonreducing conditions) containing N-linked carbohydrate chains. When the cells are treated with phosphatidylinositol-specific phospholipase C, greater than 60% of total precipitable gp42-66 Ag is released in the supernatant. This phosphatidylinositol-specific phospholipase C-sensitive linkage to the plasma membrane has provided a means for the one-step purification of Mo3 by immunoaffinity chromatography. The eluted soluble Mo3 (sMo3) was greater than 90% pure as documented by the appearance of a single major protein peak on reverse phase HPLC and SDS-PAGE. The average yield was 12.1 micrograms/10(8) cells. Sufficient quantities of sMo3 have been purified to permit the determination of amino acid and carbohydrate composition. Complex N-linked carbohydrates make up nearly 50% of the glycoprotein content and contribute to its heterogeneity. An anti-Mo3 polyclonal antiserum generated from sMo3 was used to immunoprecipitate Mo3 and its precursor from biosynthetically labeled, PMA-stimulated U-937 cells or LPS-stimulated monocytes. These 35S-methionine "pulse-chase" experiments demonstrated the existence of a 40- to 42-kDa endo-beta-N-acetylglucosaminidase sensitive precursor, which over a period of 4 to 5 h gave rise to an endo-beta-N acetylglucosaminidase-resistant, but N-glycanase-sensitive 42- to 66-kDa mature form. PMID- 1869827 TI - Association of activated properdin with complexes of properdin with C3. AB - An ELISA using antibody to properdin (P), followed by antibody to C3 to detect complexes of P with C3 (P-C3), detected low levels of P-C3 complexes in human serum and plasma samples. Incubating serum for 1 h at 37 degrees C increased the amount of P-C3 and diminished factor B hemolytic activity without altering total alternative pathway activity or C3 activity in serum. When P and C3 in incubated serum were analyzed by size exclusion HPLC, complexes of P-C3 were detected at retention times corresponding to molecular mass measuring in excess of 2 x 10(6) Da. Activation of serum with zymosan or cobra venom factor greatly increased the level of P-C3 and decreased alternative pathway hemolytic activity. Chromatography of proteins eluted from serum-treated zymosan detected a peak of P at 9.7 x 10(5) Da and a peak of P-C3 at 1.5 x 10(6) Da. Functional assays for activated properdin also revealed a peak of activity at 1.5 x 10(6) Da, congruent with the peak of P-C3. Native properdin was detected at 3.9 x 10(5) Da. When native properdin was added to properdin-depleted serum and incubated for 1 h at 37 degrees C, activated properdin was detected at the same position in the chromatograph as were P-C3 complexes. We conclude that incubation of serum at 37 degrees C produces complexes of P with C3, that exposure of serum to alternative pathway activators increases the amount of P-C3, and that generation of P-C3 complexes is associated with the presence of activated P. PMID- 1869828 TI - Reduced immunogenicity and improved pharmacokinetics of humanized anti-Tac in cynomolgus monkeys. AB - The anti-Tac mAb has been shown to bind to the p55 chain of the IL-2R, block IL-2 binding and inhibit T cell proliferation. A humanized form of anti-Tac (HAT) has been constructed that retains the binding properties of murine anti-Tac (MAT). These two mAb were evaluated in cynomolgus monkeys to compare relative immunogenicity and pharmacokinetic properties. Monkeys treated with HAT daily for 14 days exhibited anti-HAT antibody titers which were 5- to 10-fold lower than their MAT-treated counterparts and these antibodies developed later than in the MAT-treated monkeys. Two of four monkeys receiving a single injection of MAT developed anti-MAT antibodies, whereas none of four monkeys developed antibodies after a single treatment with HAT. In monkeys injected with either HAT or MAT daily for 14 days, the anti-antibody titers induced were inversely related to the amount of anti-Tac administered. Antibodies that developed against MAT were both anti-isotypic and anti-idiotypic, whereas those developed against HAT appeared to be predominantly anti-idiotypic. The pharmacokinetic properties, that is the half life and area under the curve values, of HAT were also significantly different from those of MAT. The area under the curve values for HAT in naive monkeys were approximately twofold more than those for MAT, and the mean serum half-life of HAT was 214 h, approximately four- to fivefold more than MAT. These pharmacokinetic values were reduced in monkeys previously sensitized with HAT or MAT suggesting that the presence of anti-antibodies altered these parameters. PMID- 1869829 TI - The function of lymphocyte proteases. Inhibition and restoration of granule mediated lysis with isocoumarin serine protease inhibitors. AB - To kill other cells, lymphocytes can exocytose granules that contain serine proteases and pore-forming proteins (perforins). We report that mechanism-based isocoumarin inhibitors inhibited the proteases and inactivated lysis. When inhibited proteases were restored, lysis was also restored, indicating that the proteases were essential for lysis. We found three new lymphocyte protease activities, "Asp-ase,""Met-ase," and "Ser-ase," which in addition to ly-tryptase and ly-chymase, comprise five different protease activities in rat RNK-16 granules. The general serine protease inhibitor 3,4-dichloroisocoumarin (DCI) inhibited all five protease activities. Essentially all protease molecules were inactivated by DCI before lysis was reduced, as determined from DCI's second order inhibition rate constants for the proteases, the DCI concentrations, and the times of pretreatment needed to block lysis. The pH favoring DCI inhibition of lysis was the pH optimum for protease activity. Isocoumarin reagents acylate, and may sometimes secondarily alkylate, serine protease active sites. Granule proteases, inhibited by DCI acylation, were deacylated with hydroxylamine, restoring both the protease and lytic activities. Hydroxylamine does not restore alkylated proteases and did not restore the lytic activities after inhibition with 4-chloro-7-guanidino-3-(2-phenylethoxy)-isocoumarin, a more alkylating mechanism-based inhibitor designed to react with tryptases. It is improbable that isocoumarin reagents directly inactivated pore-forming proteins because 1) these reagents require protease activation, 2) their nonspecific effects are alkylating, and 3) alkylated proteins are not restored by hydroxylamine. We conclude that serine proteases participate in lysis when lysis is mediated by the complete assembly of granule proteins. PMID- 1869830 TI - Aggregated bovine IgG inhibits mannose receptor expression of murine bone marrow derived macrophages via activation. AB - We previously described the presence of an inhibitory protein contained in the 20 to 40% (NH4)2SO4 precipitable fraction of FCS that down-regulates expression of mannose receptors on bone marrow-derived macrophages. We now identify aggregated bovine IgG as the main inhibitory component. Heat-aggregated bovine IgG was capable of down-regulating expression of the macrophage mannose receptor in a dose-dependent manner without inducing changes in ligand affinity whereas neither F(ab')2 fragments nor nonaggregated IgG displayed any inhibitory effect. Depleting of IgG from heat inactivated FCS by protein G affinity chromatography completely removes the inhibitory activity. Moreover, readdition of the Ig eluate from the protein G chromatography column restored inhibition in a dose-dependent manner. Macrophages were able to clear exogenously added aggregated bovine IgG, thus leading to loss of inhibitory activity in macrophage-conditioned media as compared to sham-conditioned media containing aggregated IgG. These results indicate that aggregated IgG down-regulates mannose receptor expression by macrophage activation via interaction with Fc-gamma R. PMID- 1869831 TI - Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis. AB - Rodents infected with the nematode parasite Nippostrongylus brasiliensis (Nb) develop intestinal mastocytosis, eosinophilia, and elevated serum IgE levels. Although IL-4 and IL-5 are necessary for stimulation of IgE synthesis and eosinophilia, respectively, the cytokines that regulate gut mast cell hyperplasia have not been identified. To address this question, 6- to 8-wk-old BALB/c mice were injected on day 0 and day 7 of Nb infection with a rat anti-mouse IL-4 mAb, and with polyclonal sheep (day 0) and rabbit (day 7) anti-mouse IL-3 IgG antibodies. Additional Nb-infected mice received equal doses of isotype- and species-matched control antibodies. Mice were sacrificed on days 12 or 13 post infection, and mucosal mast cells (MMC) in sections of the small intestine were enumerated. Nb infection induced a 25- to 40-fold increase in MMC over that observed in uninfected controls. Anti-IL-3 or anti-IL-4 alone suppressed the Nb induced MMC response by 40 to 50%, whereas both antibodies combined suppressed the MMC response by 85 to 90%. Anti-IL-3 alone had no effect on the serum IgE levels, which were essentially abrogated in the Nb-infected mice treated with anti-IL-4. Blood eosinophilia was not affected by treatment with anti-IL-3 and/or anti-IL-4. These studies demonstrate that IL-3 and IL-4 are physiologically important stimuli of mastocytosis in vivo, and suggest therapeutic interventions that may counteract adverse host responses to allergens as well as to parasites. PMID- 1869832 TI - Ly-49 multigene family. New members of a superfamily of type II membrane proteins with lectin-like domains. AB - Ly-49 (YE1/48, A1) is a dimer protein expressed on subpopulations of murine NK cells. It is a member of a superfamily of type II transmembrane proteins containing carbohydrate recognition domains (CRD). In the mouse genome, the detection of multiple restriction fragments that cross-hybridize with Ly-49 cDNA probes suggests the presence of related genes. In this study, we have isolated several genomic clones encoding portions of CRD sequences highly homologous to the CRD of Ly-49. By using primers based on the consensus sequences of the genomic clones, expression of Ly-49-related genes was detected by the polymerase chain reaction in various organs, including lung, kidney, liver, spleen, and thymus. Two full-length cDNA clones that are highly homologous to the Ly-49 gene were subsequently isolated from a lung cDNA library. At the nucleotide level, the two clones are 72% and 80% identical to Ly-49 in their translated regions, but their sequences are different from those of the genomic clones characterized to date. The two cDNA clones potentially encode type II transmembrane proteins containing CRD that are very similar to Ly-49. These amino acid sequences are also homologous to other members of the superfamily of CRD-containing type II transmembrane proteins, including hepatic lectins and the low affinity IgER (CD23). The homology is most evident in the CRD but is also significant in other domains. These results demonstrate the existence of several functional genes that are highly related to Ly-49. These genes comprise a subfamily within the superfamily of type II transmembrane proteins containing CRD. PMID- 1869833 TI - Lymphokine-activated killer cells are rejected in vivo by activated natural killer cells. AB - A 4-h in vivo cytotoxicity assay was used to study the fate of implanted IL-2 generated, lymphokine-activated killer (LAK) cells in mice undergoing an activated NK cell response. 125Iododeoxyuridine-labeled LAK cells were rejected from selected organs of C57BL/6 mice infected with lymphocytic choriomeningitis virus or treated with IL-2 or the IFN inducer poly I:C. This rejection was abrogated by the selective depletion of NK cells with antibodies to asialo-GM1 and NK1.1 Ag. Similar results were noted when LAK cells were generated from the spleens of B and T cell-deficient severe combined immunodeficiency mice and when LAK cells were implanted into severe combined immunodeficiency mice. These data indicate that NK cells activated by virus infections or by IL-2 infusions directly or indirectly eliminate implanted LAK cells. Because LAK cells are used in the treatment of certain human cancers, the strategy of accompanying this therapy with IL-2 infusions should be reassessed in light of these results. PMID- 1869834 TI - Comparison between strains of human T lymphotropic virus type I isolated from inhabitants of the Solomon Islands and Papua New Guinea. AB - Strains of human T lymphotropic virus type I (HTLV-I) isolated from T cell lines (SI-1, SI-3, and SI-5) from three individuals in separate regions of the Solomon Islands were compared with a variant (PNG-1) isolated from a healthy person in Papua New Guinea and a prototype strain from Japan (MT-2). The SI-1, SI-3, and SI 5 cell lines were predominantly CD8+. Expression of gag- and env-encoded virus specific proteins was detected in SI-1, SI-3, and SI-5 and in MT-2 cells by immunofluorescence and Western immunoblot; gag proteins p19 and p24 were absent in PNG-1 cells. HTLV-1 gag and pol gene sequences were detected in DNA extracted from SI-1, SI-3, and SI-5 cells by polymerase chain reaction; env sequences were not found in SI-5 cells. Genomic Southern analysis of PstI digests of SI-1, SI-3, and SI-5 DNA exhibited the three moderate-sized fragments typical of prototype HTLV-I. By contrast, PstI digests of PNG-1 DNA yielded two larger fragments. PMID- 1869835 TI - Seroconversion rate, mortality, and clinical manifestations associated with the receipt of a human immunodeficiency virus-infected blood transfusion in Kinshasa, Zaire. AB - To evaluate the consequences of receiving human immunodeficiency virus type 1 (HIV-1)-seropositive blood, 90 HIV-1-seronegative recipients of HIV-1 seropositive blood (case patients) and 90 HIV-1-seronegative recipients of HIV-1 seronegative blood, matched for age, sex, number of transfusions, diagnosis, and severity of illness (controls), were followed for 12 months after transfusion at Mama Yemo Hospital in Kinshasa, Zaire. Of case patients and controls, 72% were children transfused for anemia caused by malaria. Of the 46 case patients case patients alive 6 months after transfusion and for whom HIV-1 serologic results were obtained, 44 (96%) had seroconverted. Significantly more case patients (47%) than controls (16%) died within 1 year after transfusion (P less than .001). In the first 3 months after transfusion, fatigue, diarrhea, fever, cough, pruritus, pallor, oral candidiasis, polyadenopathy, hepatosplenomegaly, and rhinorrhea were observed more often among seroconverters than controls (P less than .04). Six percent of case patients and no controls had developed clinical AIDS after 12 months of follow-up. These findings underscore the urgent need for appropriate HIV screening facilities in transfusion centers worldwide. PMID- 1869836 TI - Sexually transmitted diseases in a population of intravenous drug users: association with seropositivity to the human immunodeficiency virus (HIV). AB - The association between human immunodeficiency virus (HIV) seropositivity and a history of sexually transmitted diseases (STDs), evidence of STDs on physical examination, and sexual and drug use practices was studied in a population of 2921 intravenous drug users (IVDUs) in Baltimore during 1988 and 1989. Overall, 24.1% were HIV-seropositive at baseline, and 60% reported a history of an STD. A significant association was found between HIV seropositivity and a history of syphilis (P = .04); both were more frequent among homosexual/bisexual men than among heterosexual IVDUs. In multivariate analysis, a history of syphilis was independently associated with HIV seroprevalence in homosexual/bisexual male IVDUs, of whom 90% reported a history of sexual intercourse with women. Cocaine injection was independently associated with HIV seropositivity but not a history of syphilis on multivariate analysis. STDs, indicative of unsafe sex practices, are common in this population; efforts are needed to prevent sexual transmission of HIV infection among IVDUs and their sex partners. PMID- 1869837 TI - Fertility parameters in men infected with human immunodeficiency virus. AB - The effect of human immunodeficiency virus type 1 (HIV) infection on semen parameters that assess fertility was investigated in 50 semen specimens from 21 asymptomatic or minimally symptomatic HIV-seropositive men and 3 specimens from 3 men with AIDS. HIV was isolated from 15 (30%) of 50 specimens from asymptomatic or minimally symptomatic persons and from 1 of 3 specimens from patients with AIDS. The men with AIDS all had pyosemia and grossly abnormal sperm. In contrast, semen specimens from other seropositive men did not differ significantly from semen specimens from healthy seronegative semen donors. No abnormality in sperm count, morphology, numbers or types of leukocytes in semen, or other seminal parameters was associated with HIV shedding in semen. Zidovudine therapy did not affect sperm morphology or seminal characteristics. Thus, although patients with AIDS had abnormal semen, the laboratory parameters that assess fertility were not affected by shedding of HIV in semen or concomitant therapy with zidovudine. PMID- 1869838 TI - Streptokinases produced by pathogenic group C streptococci demonstrate species specific plasminogen activation. AB - The species specificities of plasminogen activation and binding of plasmin by pathogenic group C streptococci isolated from humans, horses, and pigs were examined. Of 56 streptococcal isolates, 52 elaborated plasminogen activator activity and 49 of these had specificity for plasminogen of the homologous host. Analysis of supernatants from 13 isolates indicated that the plasminogen activator activity resulted from secreted streptokinases. These 13 streptokinases were antigenically related and bound all three plasminogens, indicating that the binding recognition sites were conserved despite the observed species-specific activation. In addition, all group C isolates tested demonstrated surface receptors that bound human, equine, and porcine plasmin. Species-specific plasminogen activation may be an early step in events resulting in infection and may account for the species preference of certain streptococci. PMID- 1869839 TI - A streptococcal erythrogenic toxin preparation augments natural killer activity of peripheral blood mononuclear cells. AB - Natural killer (NK) activity in peripheral blood mononuclear cells is augmented by products released by two different strains of streptococci. This property is due at least in part to an erythrogenic toxin (ET). A preparation of physiologically active ET from strain NY5 group A beta-hemolytic streptococci and streptococcal products (SP) derived from the culture supernatants of ATCC strain 19165 group A streptococci were both potent inducers of NK activity. An anti serum to ET reacted with two polypeptides in SP, one of which comigrated with ET when analyzed by SDS-PAGE. Using an affinity column with an antiserum to ET known to neutralize its mitogenic properties, the NK-enhancing activity of ET and SP was partly absorbed and was recovered upon elution. These findings suggest that immunologically related ETs in different streptococcal strains play a role in the activation of NK cells. This novel property of streptococci may feature in the pathogenesis of streptococcal infections and their protean manifestations. PMID- 1869841 TI - Diabetes mellitus--a newly described risk factor for infection from Salmonella enteritidis. AB - Infections due to Salmonella serotype enteritidis have increased markedly in the northeastern United States. Due to the potential severity of these infections, host risk factors for infection were determined in the largest nosocomial S. enteritidis outbreak to have occurred in the United States. In a case-control study, patients in a New York City hospital who developed infection after exposure to an S. enteritidis-contaminated meal were more likely to be medication dependent diabetics than were those who did not develop infection (17/75 vs. 7/80, Mantel-Haenszel adjusted odds ratio = 3.1, 95% confidence interval = 1.1, 8.6). Proposed mechanisms for diabetes as a risk factor for infection include decreased gastric acidity in diabetic patients and an autonomic neuropathy of the small bowel that reduces intestinal motility and prolongs gastrointestinal transit time. PMID- 1869840 TI - Effect of prior infection with virulent Shigella flexneri 2a on the resistance of monkeys to subsequent infection with Shigella sonnei. AB - All virulent shigellae have large plasmids. Plasmid-associated genes encode the expression of membrane-associated proteins (MAP), some of which correlate with the ability to invade susceptible epithelial cells. These MAP are serologically related in all of the shigella serotypes and evoke an antibody response after infection. To determine whether the MAP have a significant role in protection, 24 monkeys were infected with virulent Shigella flexneri 2a. After recovery, one group (with controls) was rechallenged with S. flexneri 2a; another group (with controls) was fed Shigella sonnei. The animals that were rechallenged with S. flexneri 2a were protected, while those that were fed S. sonnei experienced the same incidence of disease as controls. No differences in serum immune response to MAP after primary infection with S. flexneri were detected in immunoblots using lysates of S. flexneri or S. sonnei or in ELISA using water extracts of these strains. PMID- 1869842 TI - Absence of transplacental transmission of Lyme disease spirochetes from reservoir mice (Peromyscus leucopus) to their offspring. AB - Lyme disease spirochetes (Borrelia burgdorferi) are naturally maintained in an enzootic cycle mainly by vector ticks (Ixodes dammini) infesting white-footed mice (Peromyscus leucopus). Suggestions that mice may become infected without exposure to ticks prompted a study to evaluate whether mice could transmit spirochetes transplacentally to their offspring. Mice were live-captured in two Massachusetts sites where Lyme disease spirochetes are intensely enzootic. Pregnant females were housed separately in the laboratory through delivery, and mothers and their offspring were caged together until weaning. Each female and two offspring were then examined for evidence of infection serologically and by tick xenodiagnosis. All 14 mother mice examined produced infected ticks and exhibited serum antibodies to B. burgdorferi. However, none of 28 offspring tested produced infected ticks and only a few had evidence of circulating antibody. In a separate experiment, no young CD-1 mice, born of infected mothers, had IgM antibody to B. burgdorferi. It would appear that immature mice are not transplacentally infected with spirochetes and must be exposed to infected ticks before becoming infected and infective themselves. PMID- 1869843 TI - The role of fluconazole in the early treatment and prophylaxis of experimental invasive aspergillosis. AB - The efficacy of fluconazole against Aspergillus fumigatus was assessed in an immunosuppressed temporarily leukopenic rabbit model of invasive aspergillosis. Therapy with fluconazole at 60 or 120 mg/kg/day was begun 24 h after lethal challenge and compared to that with amphotericin B at 1.5 mg/kg/day. Fluconazole reduced mortality compared with that in untreated controls and at 120 mg/kg/day reduced the tissue burden of A. fumigatus 10- to 100-fold in liver, kidney, and lung. However, amphotericin B was more effective in sterilizing tissues. Both fluconazole and amphotericin B dramatically decreased or eliminated circulating aspergillus antigen. Prophylaxis with fluconazole, begun 48 h before sublethal challenge, sterilized liver and kidney tissues and significantly reduced the tissue burden in lung. Early treatment with fluconazole reduced mortality and reduced antigenemia but did not sterilize tissues. Fluconazole prophylaxis at these doses prevented dissemination of invasive aspergillosis. Fluconazole was shown to have activity in the early treatment and prophylaxis of experimental invasive aspergillosis. PMID- 1869844 TI - Association of cervical ectopy with heterosexual transmission of human immunodeficiency virus: results of a study of couples in Nairobi, Kenya. AB - To identify risk factors involved in heterosexual transmission of human immunodeficiency virus (HIV), a cross-sectional study of HIV-seropositive men and their spouses was conducted in Nairobi, Kenya. Of 70 spouses, 40 (57%) were seropositive and 30 (43%) were seronegative for HIV. In univariate analysis, the presence of cervical ectopy (odds ratio, 4.7; P = .006) was the only statistically significant variable associated with HIV infection in women. After controlling for possible confounding variables using multivariate logistic regression analysis, the presence of cervical ectopy (odds ratio, 5.0; P = .007) remained the only independent predictor of HIV seropositivity. These findings suggest that cervical ectopy may be a newly identified risk factor for heterosexual transmission of HIV. PMID- 1869845 TI - Outbreak of group A streptococcal bacteremia in Sweden: an epidemiologic and clinical study. AB - The nationwide incidence of group A streptococcal bacteremia in Sweden was 1.8 per 100,000 population in 1987. During the winter season 1988-1989, the reported cases rate doubled and then declined to the previous level. The peak was due to a type T1/M1 Streptococcus pyogenes strain associated with an increased case fatality rate (33% vs. 15% for other T types). The highest incidence rates were found in the age groups less than 12 months and greater than 70 years. Among a sample of 79 patients hospitalized in November or December 1988, a portal of entry, mainly cutaneous, was recognized in 89% of the patients and concomitant conditions in 67%. Among the clinical findings were signs of skin or soft tissue infection (41%), local or generalized pain (41%), vomiting or diarrhea (24%), cough (18%), and upper respiratory tract symptoms (12%). A fatal outcome was associated with high age, lower respiratory tract or unknown focus, leukopenia on admission, start of antibiotic therapy greater than 6 h after the patient's initial contact with a physician, and a rapid clinical course including multiple organ failure. Renewed awareness of the many facets of fulminant streptococcal infection represents one approach to minimize the case fatality rate. PMID- 1869846 TI - Comparison of the early dynamics of systemic prostacyclin release after administration of tumor necrosis factor and endotoxin to healthy humans. AB - Excessive production of prostaglandins may be of importance for the development of organ damage in generalized infection. To investigate the role of tumor necrosis factor (TNF) in systemic prostacyclin release in gram-negative septicemia, the plasma concentrations of its stable metabolite 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha) were sequentially measured after intravenous bolus injections of recombinant human TNF (50 micrograms/m2; n = 6) and Escherichia coli endotoxin (2 ng/kg; n = 3) in healthy men. TNF induced a rapid increase in plasma 6-keto-PGF1 alpha from 0.11 +/- 0.01 to 0.44 +/- 0.15 ng/ml after 30 min (P less than .001). Endotoxin also elicited a rise in plasma 6 keto-PGF1 alpha, but peak values were reached only after 90 min (from 0.07 +/- 0.01 to 0.19 +/- 0.04 ng/ml; P less than .002). These results indicate that TNF may serve as an intermediate factor in systemic elaboration of prostacyclin in endotoxemia and gram-negative septicemia. PMID- 1869847 TI - Ciprofloxacin treatment of drug-resistant falciparum malaria. AB - A randomized, open study of high-dose ciprofloxacin (750 mg every 12 h) in uncomplicated falciparum malaria was conducted in Thailand. No patient completed the planned 1-week treatment course. Because of rising parasitemia (threefold higher at 36 h than on admission) and deterioration of clinical status, three individuals required quinine treatment 36 h after commencing ciprofloxacin; a fourth was given quinine at 54 h. The study was terminated early for safety reasons after only four ciprofloxacin and four control patients had been enrolled. Ciprofloxacin was well absorbed and efficiently entered erythrocytes; median plasma and red cell concentrations 90 min after the first dose were 4.0 (range, 3.7-6.8) and 5.1 (3.8-6.0) micrograms/ml, respectively. However, 50% inhibition of parasite growth in vitro required 6.6 micrograms/ml, (5.6-9.6). Ciprofloxacin should not be used alone to treat chloroquine-resistant falciparum malaria. PMID- 1869848 TI - Pentoxifylline prevents murine cerebral malaria. AB - Pentoxifylline, a widely used methylxanthine, was tested for its capacity to prevent cerebral malaria (CM) in Plasmodium berghei ANKA-infected CBA/Ca mice. Nine of 12 control mice developed neurologic signs and died from CM approximately 2 weeks after infection. All 12 mice treated with daily intraperitoneal pentoxifylline (1 mg) for 10 days after infection did not develop CM. All surviving mice developed high parasitemia and severe anemia and died 2 weeks later without neurologic signs. In pentoxifylline-treated mice, serum tumor necrosis factor (TNF) bioactivity was nondetectable, whereas control mice had high TNF levels on day 6 after infection. These findings were supported by in vitro investigations of malaria antigen-induced TNF synthesis. Northern blot analysis of TNF mRNA from stimulated macrophages showed that pentoxifylline inhibited TNF expression at the transcription level, and TNF bioactivity in supernatants was strongly depressed. These findings make pentoxifylline a potential candidate for study as a supportive agent in human CM. PMID- 1869849 TI - Contribution of pyrazinamide to antituberculosis chemotherapy. PMID- 1869850 TI - Effect of pyocyanin and 1-hydroxyphenazine on the assay of lactate dehydrogenase activity. PMID- 1869851 TI - Entamoeba hartmanni: missing or misidentified? PMID- 1869852 TI - Salivary IgA antibody detection in invasive amebiasis and in asymptomatic infection. PMID- 1869853 TI - Primary human immunodeficiency virus infection mimicking syphilis. PMID- 1869854 TI - Unusually high level of a tumor-associated antigen in the serum of human immunodeficiency virus-seropositive individuals. PMID- 1869855 TI - Naturally acquired immunity: a means of resistance to Mediterranean spotted fever? PMID- 1869856 TI - Failure of intrathecal tetanus antitoxin in the treatment of tetanus neonatorum. PMID- 1869857 TI - Safety and efficacy of liposomal amphotericin B in treating AIDS-associated disseminated cryptococcosis. PMID- 1869858 TI - Development of histoplasmosis in a human immunodeficiency virus-infected patient receiving fluconazole. PMID- 1869859 TI - Sporobolomyces infection in an AIDS patient. PMID- 1869860 TI - Mefloquine-resistant malaria induced by inappropriate quinine regimens? PMID- 1869862 TI - [24th annual meeting of the JOA Musculoskeletal Tumor Society. Tokyo, July 19-20, 1991. Abstracts]. PMID- 1869861 TI - Expression of the genes of class I interferons and interleukin-6 in individual cells. AB - The use of a highly sensitive method of in situ hybridization capable of detecting one copy of interferon (IFN) mRNA per cell coupled with quantitative analysis of cytokine mRNA showed that the number of copies of mRNA per cell was directly proportional to the logarithm of the number of silver grains formed over that cell. More than 90% of both virus-induced human Namalwa and mouse C243 cells exhibited grain counts significantly greater than background values following in situ hybridization with riboprobes complementary to human IFN- alpha and mouse IFN- beta mRNA, respectively. Labeling was shown to be specific, as the labeled probe was displaced by a 200-fold excess of the specific unlabeled probe but not by a 200-fold excess of an unrelated probe. Although the large majority of cells within a population responded to induction, considerable variation was observed, however, in the content of IFN mRNA per cell: 24% of induced C243 cells contained more than 50 copies of IFN-beta mRNA per cell while 60% of the cells contained 10 copies or less. Low levels of IFN mRNA were also detected in both uninduced C243 cells and uninduced Namalwa cells. Five to 10% of peripheral blood mononuclear cells from normal donors expressed INF-alpha mRNA following induction in vitro. Approximately 1% of untreated peripheral blood mononuclear cells also exhibited low levels of IFN-alpha mRNA. Analysis of interleukin-6 (IL-6) mRNA showed that 97% of TNF-induced human MG63 cells contained IL-6 mRNA, although, again, the amount varied considerably from cell to cell. PMID- 1869863 TI - Plasma levels of glucose, ketone bodies, lactate, and alanine in the vascular supply to and from the brain of the adult American bullfrog (Rana catesbeiana). AB - Serial, paired blood samples were collected via cannulae chronically placed in the common carotid artery (A) to and the internal jugular vein (V) from the brain of the fasted adult American bullfrog (Rana catesbeiana). Plasma glucose, beta hydroxybutyrate, acetoacetate, lactate, and alanine levels were measured by standard enzymatic procedures. Cannula failure ended sampling after 1-2 days in most animals. The common carotid artery plasma metabolite levels were greatest at the time of surgery and subsequently declined to relatively stable levels. The summarized data indicated glucose uptake and alanine release by the brain, but no significant beta-hydroxybutyrate or lactate A-V percentage changes. Initially, acetoacetate levels also were measured, but were discontinued in favor of continued beta-hydroxybutyrate determinations when no significant A-V percentage changes occurred. Separate analysis of the metabolite levels during the surgery and recovery period (less than or equal to 24 hr) and the "normal" under the experimental conditions period (greater than 24 hr) revealed that summarizing the data masked important A-V percentage changes during the two different physiological conditions. Glucose was the only metabolite extracted by the brain during the less than or equal to 24 hr period of elevated and subsequently declining metabolite levels. In contrast, glucose uptake did not occur during the greater than 24 hr period of stable levels, but there was lactate release. If the bullfrog brain stores substantial glycogen as do the other ectothermic vertebrates studied, glucose uptake when plasma levels are elevated, for example after feeding, may serve both to fuel the brain and to replenish endogenous glycogen reserves that may be mobilized to provide glucose for the brain after plasma glucose levels return to normal. Assuming that mammalian and bullfrog metabolic pathways are the same, the release of lactate and alanine by the brain, possibly to remove excess pyruvate and to regenerate NAD+, is consistent with this hypothesis. It remains to be determined for how long endogenous energy sources alone can support the bullfrog brain, and if plasma glucose, ketones, and/or other energy sources are extracted as endogenous brain fuels become exhausted. PMID- 1869864 TI - Development and DNA polymerase activities in cultured preimplantation mouse embryos: comparison with embryos developed in vivo. AB - Embryos from superovulated female mice that developed in vitro from the two-cell stage were compared with in vivo embryos with respect to yield of blastocytes, number and types of cells, morphology in histologic section, and DNA polymerase activities. Significantly more embryos developed into blastocytes in vitro (93%) than in vivo (18%). Inner cell mass (ICM) cells comprised approximately 30% of total cells in late morula/early blastocyst stage embryos developed either in vitro or in vivo. However, the in vitro embryos developed approximately half the number of total cells as in vivo embryos, did not develop endoderm, and did not develop abembryonic trophoblast cells with morphologic characteristics of late preimplantation in vivo embryos. DNA-dependent DNA polymerase activities in in vitro embryos decreased in correspondence with the decrease in cell number resulting in per cell levels comparable to in vivo embryos. In contrast, the poly (A).oligo(dT)-dependent DNA polymerase activity was the same in embryos developing either in vitro or in vivo, indicating different regulatory mechanisms for the two enzyme activities. A variety of nutrients and growth factors in the culture medium did not increase cell numbers or DNA polymerase activities in embryos cultured for 3 days; extending the culture an additional 24 hours resulted in a loss of ICM cells and decreases in both DNA polymerase activities. These results show that the retarded growth of embryos in vitro is equally distributed between ICM and trophoblast, is not reversed by culture conditions that include serum growth factors, and is not due to decreased cellular levels of DNA polymerase activities. PMID- 1869865 TI - Effect of photoperiod on the rate of 3H-thymidine incorporation of epididymal principal cells in adult Syrian hamsters. AB - Photoperiod-induced cycles of gonadal regression and recrudescence in the Syrian hamster were used to determine if epididymal growth in adults involves mitotic activity of principal cells. In Experiment 1, the following groups of adult hamsters were examined: induced recrudescing (5L:19D [5 hr light and 19 hr dark] for 13 wk followed by 14L:10D for at least 3 wk), spontaneous recrudescing (5L:19D for 25 wk), and active gonadal state (14:10D). In Experiment 2, adult hamsters were divided into the following groups: induced recrudescing, active, and regressed (5L:19D for 16 wk). Hamsters received subcutaneous injections of 0.5 microCi 3H-thymidine/g body weight three times/wk for 3 wk. The epididymis was fixed in a glutaraldehyde followed by osmium, embedded in Epon 812, and sectioned at 1 micron. Slides were dipped in Kodak NTB-3 emulsion, exposed for 2 or 3 months, developed, and evaluated for isotopic labeling of principal and basal cell nuclei by scoring 500 to 1,000 nuclei. In Experiment 1, the percentages of labeled principal cell nuclei for the induced recrudescing, spontaneous recrudescing, and active groups were 26 +/- 2%, 23 +/- 5%, and 9 +/- 1%, respectively. Considering the intermittent availability of 3H-thymidine during 21 days, this represents daily recruitment of 6.3%, 5.6%, and 2.2%, respectively. In Experiment 2, the percentages of labeled principal cell nuclei for induced recrudescing, active, and regressed groups were 12 +/- 4%, 3 +/- 1%, and 4 +/- 1%, respectively. There was no effect of photoperiod on labeling pattern of basal cells (1.5 +/- 0.6%, 1.2 +/- 0.1%, 0.4 +/- 0.1% for the three photoperiod groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869866 TI - The present status of akathisia. AB - Akathisia is a common and distressing side effect of antipsychotic and some other psychotropic medications. This paper reviews the current state of knowledge of its clinical features, pathophysiology, and treatment. Restless legs syndrome and akathisia associated with Parkinson's disease are discussed in so far as they help understand drug-induced akathisia. The complexity of the disorder, and the difficulty in characterizing and quantifying it, may explain why researchers have relatively neglected akathisia for so long. The recent upsurge of research interest promises the hope of a better understanding of its pathophysiology so that effective therapy may result. PMID- 1869867 TI - Gender differences in the specificity of alcoholism transmission among the relatives of opioid addicts. AB - Gender differences in the specificity of drug versus alcohol transmission were examined among 201 opioid addicts and their 877 first-degree relatives using direct interviews and a structured family history method based on the Schedule for Affective Disorders and Schizophrenia Research Diagnostic Criteria. A strong association of parental alcoholism with alcoholism among the proband addicts was found, suggesting some specificity for drug versus alcohol abuse. We also found that among the 477 siblings, those with alcoholism alone did not have parents with drug abuse and those parents with drug abuse did not have children with alcoholism alone. Rates of parental alcoholism were higher in alcoholic female than in alcoholic male probands, suggesting greater female "loading" was needed in order to become alcoholic. This increased loading in women was also found among the siblings, but alcoholic parents appeared to transmit a nonspecific tendency for either drug or alcohol abuse to their female children. Thus, it may take a greater "dose" of parental transmission for a woman to become a substance abuser, and transmission of alcoholism may be specific in men, but not in women. PMID- 1869868 TI - The antisocial personality disorder diagnosis in substance abusers: problems and issues. AB - This paper examines the question of whether antisocial personality disorder (APD) can be considered a viable substance abuse typology. The data for APD substance abusers are first reviewed with respect to six properties that apply to establishing the validity of a clinical typology. This is followed by a brief description of the historical context and development of current conceptualizations of antisocial personality. Some possible sources of diagnostic unreliability and instability that could serve to limit the validity of the APD diagnosis are then discussed. Finally, evidence indicating considerable psychiatric heterogeneity within APD substance abusers is described. The findings indicate that although APD substance abusers satisfy many of the criteria for a clinical subtype, the fit is sufficiently imprecise to suggest the need for further refinement. We attempt to point out some of the critical questions, issues, and lines of research that could help to guide future efforts to clarify, refine, and revise the APD formulation, particularly as it applies to substance abusers. PMID- 1869869 TI - Subjective experiences related to alcohol use among schizophrenics. AB - Comorbid alcohol use disorders are common in schizophrenia. Although a variety of explanatory hypotheses involving self-medication have been proposed, few data available regarding schizophrenic patients' subjective experiences while using alcohol. We report interview data from 75 DSM-III-R schizophrenic outpatients regarding their subjective responses to alcohol. Over half of our sample reported that alcohol improved social anxiety, tension, dysphoria, apathy, anhedonia, and sleep difficulties. Other nonpsychotic experiences were frequently improved as well. In contrast, no more than 15% of subjects reported that alcohol relieved any specific psychotic symptom; similar proportions of subjects reported that alcohol aggravated psychotic symptoms. Reporting that alcohol had a positive effect on nonpsychotic experiences was associated with having lifetime alcohol use disorders. Reporting that alcohol relieved psychotic symptoms was associated both with having lifetime alcohol use disorders and with the number of psychotic symptoms reported. We discuss the implications of these findings for understanding alcohol abuse and dependence among schizophrenics. PMID- 1869870 TI - Dysphoria in male alcoholics with a history of hallucinations. AB - This paper examines severity of depressive symptoms, as measured by the Beck Depression Inventory, in chronic alcoholics with and without a history of hallucinations. We found a) alcoholics entering alcohol treatment who have experienced hallucinations during detoxification report higher levels of subjective depression than alcoholics who have never experienced hallucinations, b) the level of subjective depression in alcoholics with a history of hallucinations remains higher at the end of inpatient alcohol treatment than in alcoholics without hallucinations, and c) hallucination is the important variable; alcoholics with blackouts, seizures, and delirium tremens, do not experience higher levels of depression during detoxification. The reporting of a significantly higher level of depressive symptoms by alcoholics with a history of experiencing hallucinations during withdrawal suggests that in some alcoholics, there exists a vulnerability for mood abnormalities which includes a predisposition toward other abnormal mental phenomena such as perceptual distortions. PMID- 1869873 TI - Quality of object relations versus interpersonal functioning as predictors of therapeutic alliance and psychotherapy outcome. AB - The purpose of the study was to compare an interview measure of quality of object relations to questionnaire and interview measures of recent interpersonal functioning with respect to the prediction of therapeutic alliance and psychotherapy outcome. The sample consisted of 64 patients who had received approximately 20 sessions of short-term individual psychotherapy within a controlled, clinical-trial investigation. Ratings of therapeutic alliance were provided independently by the patient and the therapist after each session. Outcome measures, which were provided by three sources (patient, therapist, and independent assessor), covered the areas of interpersonal functioning, psychiatric symptomatology, self-esteem, and life satisfaction. Quality of object relations, which characterizes the patient's lifelong pattern of relationships, was the best predictor. It was significantly related to patient-rated and therapist-rated therapeutic alliance and to patient improvement of both general symptomatology and specific target problems. The study also replicated previous studies that have reported significant relationships between therapeutic alliance and therapy outcome. The advantages of pretherapy predictors of therapy outcome, such as quality of object relations, are discussed. PMID- 1869871 TI - Psychiatric disorders among poor victims following a major disaster: Armero, Colombia. AB - We evaluated 102 adult victims of low socioeconomic status living in tent camps 8 months following the Armero disaster in Colombia to ascertain the level of psychiatric morbidity. Ninety-one percent of the subjects identified by the screening instrument as being emotionally distressed met DSM-III criteria for a psychiatric disorder. The most frequent diagnoses were posttraumatic stress disorder and major depression. These findings indicate that a simple screening instrument can be reliably used for the detection of significant emotional problems among disaster victims. They also show that these victims are not merely distressed; rather, they present clear and treatable psychiatric disorders that center on anxiety and depression. Interventions for their adequate management need to be designed, implemented, and evaluated. In a developing country, however, the high prevalence of mental disorders among disaster victims far exceeds the specialized mental health resources. The general health sector, particularly the primary level of care, must participate actively in the delivery of mental health services to meet this need, particularly for a socioeconomically disadvantaged population. The narrow range of psychiatric disorders detected among the disaster victims makes it possible to circumscribe the training of the primary care worker in disaster mental health to these priority conditions. PMID- 1869874 TI - Carbamazepine for atypical psychosis with episodic hostility. PMID- 1869872 TI - Posttraumatic stress disorder among children clinically diagnosed as borderline personality disorder. AB - Using the Diagnostic Interview for Children and Adolescents, Revised Version (DICA-C-R), the authors evaluated 19 children ages 7 to 14 who had recently been clinically diagnosed as borderline personality disorder by DSM-III-R criteria. The results reveal that 78.9% of these children reported significant traumatic experiences, with 36.8% fitting DICA-C-R criteria for posttraumatic stress disorder. These findings raise the possibility that a diagnosis of borderline personality in childhood can often represent posttraumatic stress disorder. PMID- 1869875 TI - Drug-related alopecia in patients treated with tricyclic antidepressants. PMID- 1869876 TI - GABA-like immunoreactivity in the developing chick retina: differentiation of GABAergic horizontal cell and its possible contacts with photoreceptors. AB - The morphology of gamma-aminobutyric acid (GABA)-containing horizontal cells was examined in mature and developing chick retinas by GABA immunocytochemistry. In the outer plexiform layer of the mature retina, GABA-immunoreactive components were located in three different sublayers. In the inner (vitreal) layer most positively-stained fibres were laterally oriented processes from horizontal cells. Thick processes were found in the middle layer, and the relatively thin fibres in the outer (scleral) layer showed a concave curvature, suggesting their termination on photoreceptor terminals. By electron microscopy it was found that the principal cone pedicles were usually indented by immunoreactive lateral neurites of horizontal cells but that rod spherules faced only occasionally immunoreactive fibres. Accessory cones and single cones were also not usually indented by immunoreactive fibres. These observations may indicate that horizontal cells regulate the excitation of cone photoreceptors by several different inhibitory mechanisms. During retinal development, horizontal cells begin to extend lateral fibres by the ninth embryonic day, and some GABAergic horizontal cells also possess inwardly extending fibres until embryonic day 11. Between embryonic days 13 and 15, some immunoreactive cells were found among the bipolar cells, suggesting that they were still migrating to their final position. On embryonic day 17, the staining pattern was very similar to that of the mature retina. These results suggest that GABA immunohistochemistry may be an excellent tool for studying horizontal cell differentiation. PMID- 1869877 TI - Gracile nucleus of streptozotocin-induced diabetic rats. AB - This study reports ultrastructural changes in the gracile nucleus of male Wistar rats after streptozotocin-induced diabetes. During the acute phase (3-7 days) degenerating electron-dense dendrites and axon terminals were dispersed in the neuropil. Degenerating dendrites were characterized by an electron-dense cytoplasm, swollen mitochondria, dilated endoplasmic reticulum and scattered ribosomes. Degenerating axon terminals were characterized by an electron-dense cytoplasm and clustering of small spherical agranular vesicles. Degenerating axon terminals may form part of a synaptic glomerulus with a central electron-dense dendrite, or they may form the central element of a synaptic glomerulus. These degenerating profiles were absent in the gracile nucleus of the 3 and 7 days insulin-treated post-streptozotocin rats. Macrophages were present in the neuropil and were in the process of engulfing neuronal elements. During the medium phase (1-6 months), most of the degenerating dendrites and axon terminals had been engulfed or removed by macrophages. During the late phase (9-12 months) a second wave of degeneration occurred in the gracile nucleus, similar to the acute phase. During the medium and late phases, dystrophic axonal profiles were also significantly increased in the rats after streptozotocin treatment. It is concluded that the ultrastructural changes observed in the gracile nucleus in the present study were the result of streptozotocin-induced diabetes rather than a toxic effect of streptozotocin, even in the acute phase. PMID- 1869878 TI - Selectivity of kainic acid as a neurotoxin within the dorsal lateral geniculate nucleus of the cat: a model for transneuronal retrograde degeneration. AB - In situ injections of the cytotoxin kainic acid were used to make localized lesions of the dorsal lateral geniculate nucleus in the adult cat to produce a model for studying the effects of postsynaptic target loss. Kainic acid has been used extensively to produce lesions of neuronal cell bodies within the central nervous system. However, the selectivity of kainic acid has been questioned, as it may also affect afferent terminals or axons of passage. Retinal projections to degenerated geniculate nuclei were visualized 1 week after kainate injection using anterograde labelling with horseradish peroxidase and electron microscopy. The results demonstrate the presence of afferent terminals within regions of neuronal loss, and hence the selectivity of kainic acid for intrinsic geniculate neurons. PMID- 1869879 TI - Populations of rat spinal primary afferent neurons with choleragenoid binding compared with those labelled by markers for neurofilament and carbohydrate groups: a quantitative immunocytochemical study. AB - A quantitative comparison was made of the population of L5 dorsal root ganglion neurons that bind choleragenoid and the population of neurons labelled by RT97, an anti-neurofilament antibody, SSEA3, an antibody to a globoseries carbohydrate group and 1B2, an antibody to a lactoseries carbohydrate group. Neurons with choleragenoid binding formed a population of 37% of all the cells and 94% of these were also immunoreactive to RT97. The choleragenoid-and RT97-positive groups of cells showed the same size distribution. Two small populations of cells existed which were choleragenoid negative/RT97 positive and choleragenoid positive/RT97 negative. SSEA3 immunoreactivity was found in 8% of the dorsal root ganglion neurons which were of all sizes. The 1B2 immunoreactivity was found in 32% of the dorsal root ganglion cells, the majority of which were in the small size range. More than half of the SSEA3-positive cells but only a few of the 1B2 positive neurons were labelled for choleragenoid. These results demonstrate that choleragenoid labels the majority of the light (RT97-positive) cell population and that light cells unlabelled by choleragenoid are small in number and spread across a wide size range. PMID- 1869880 TI - Transplanted type-1 astrocytes facilitate repair of demyelinating lesions by host oligodendrocytes in adult rat spinal cord. AB - The ethidium bromide model of demyelination/remyelination provides a system for studying the interactions between demyelinated axons, host glia and transplanted glia. The injection of 0.1% ethidium bromide in isotonic saline into the white matter of the spinal cord produces a glia-free demyelinating lesion which is subsequently remyelinated by Schwann cells and, to a lesser extent, oligodendrocytes. the in vitro description of an oligodendrocyte progenitor isolated from the adult CNS, together with the recognized role of type-1 astroctyes in controlling the developmental programme of perinatal O-2A progenitors, suggested the possibility that transplanted type-1 astrocytes may potentiate oligodendrocyte remyelination of the ethidium bromide lesion. Purified type-1 astrocyte cultures were prepared by removing cells of the oligodendrocyte lineage using a combination of exposure to cytosine arabinoside and complement mediated immunocytolysis. Following transplantation of purified type-1 astrocyte cultures into ethidium bromide lesions, a significant increase in the extent of oligodendrocyte remyelination was achieved. Because the purified type-1 astrocyte cultures had no demonstrable oligodendrocyte-generating potential it was concluded that the additional oligodendrocytes appearing in the type-1 astrocytes transplanted lesion were of host origin. These results indicate that type-1 astrocytes can facilitate repair of demyelinating lesions by host oligodendrocytes. The possible mechanisms whereby this facilitation occurs are discussed. PMID- 1869881 TI - Clustering of dendrites in the cerebral cortex begins in the embryonic cortical plate. AB - In this study, we have asked what organizational features can be detected in the embryonic rat cerebral cortex. We have found evidence using light microscopy, and scanning and transmission electron microscopy, that soon after the first cortical neurons join the cortical plate, their apical dendrites form clusters. These clusters are characterized by the close apposition of dendritic membranes, and by intermediate-type junctions. Clustering occurs within 24 h of cortical plate formation, at a time when the cortical plate is about six cell diameters thick, and before the cortex has any afferent input or the cortical plate any synapses. Thus the clustering of apical dendrites in the cortical plate appears to be a very early organizational feature in the development of the cerebral cortex. PMID- 1869882 TI - Axonal cytoskeleton at the nodes of Ranvier. AB - The relationship between the degree of nodal narrowing and the changes in the structure of the axonal cytoskeleton was studied in 53 fibres of mouse sciatic nerve. Nodal narrowing increased with increasing fibre calibre to reach about 20% of the internodal area in the thicker fibres. The narrowing corresponded quantitatively to a decreased number of nodal neurofilaments. Nodal microtubule numbers varied greatly, and a majority of fibres had considerably (approximately 55%) more microtubules in their nodal profile than in the internode. Nodal profiles of different calibre showed an increase in the number of filaments and of microtubules with nodal calibre, although at rates different from those in the internode. The degree of observed axon non-circularities had no discernible effect on the restructuring of the axonal cytoskeleton at the node. A transnodal transport of the axonal cytoskeleton can occur with: (1) accelerated transnodal transport of filaments, (2) stationary internodal fraction of filaments, (3) depolymerization of filaments proximal to the node and repolymerization distally, or (4) different nodal and internodal polymerization equilibria. PMID- 1869883 TI - Perineurium of sciatic nerve in normal and diabetic rodents: freeze-fracture study of intercellular junctional complexes. AB - A comparative study has been carried out using the freeze-fracture technique on the perineurium of the sciatic nerve from normal and diabetic mice (C57Bl/Ks, BALB/c and CD1 strains) and rats of various ages. The replicas showed that tight junctions connected perineurial cells both within the same cell layer (zonulae occludentes) and between adjacent layers (maculae occludentes). In neonates, a number of zonulae occludentes were characterized by short, incomplete or fragmented ridges at various intervals from each other; in adults, tight junctions appeared as 'mature' networks of interconnected, branching and/or anastomosing strands. Zonulae occludentes of diabetic mice also exhibited frequent interruption of the strands and reduction in the branching of strands. Gap junctions occurred in both zonulae and maculae occludentes of normal and diabetic rats at all ages. In the C57Bl/Ks strain such junctions occurred more frequently in zonulae occludentes of diabetic animals. It is suggested that perineurial cells are coupled by gap junctions to allow fast transfer of ions and small-sized molecules across the layers; under pathological conditions, such as diabetes, the increase in cell-to-cell signalling may be important in controlling the abnormal metabolic situation. PMID- 1869884 TI - Assessment of ultrastructure in isolated cochlear hair cells using a procedure for rapid freezing before freeze-fracture and deep-etching. AB - Separated cochlear outer hair cells and isolated strips of organ of Corti containing hair cells and supporting cells have been rapidly frozen before freeze fracture and deep-etching by immersion of samples sandwiched between two copper plates into liquid nitrogen-cooled propane: isopentane. Assessment of this procedure has shown that no significant freezing damage occurs. The ultrastructure of the hair cells revealed by freeze-fracture of these non chemically fixed preparations was generally very similar to that seen in fixed material. This indicates that the processing of cochlear tissue normally used for electron microscopy produces few obvious structural artefacts. It also demonstrated that procedures for isolating cochlear hair cells generally do not affect cell structure significantly. However, some isolated hair cells did show abnormalities within the membranes of the lateral cisternae. Such membrane alterations, which would not be identified by light microscopy, occurred to a variable extent but were more commonly present after prolonged periods in maintenance medium. Deep-etching of the preparations to examine extracellular features around stereocilia revealed clearly lateral cross-links between stereocilia. However, tip-links could not be positively identified in either unfixed or prefixed preparations. PMID- 1869885 TI - Linear arrays of homogeneous mast cells in the dura mater of the rat. AB - Using fluorescence histochemistry, 5-HT, histamine and heparin were colocalized in a large population of cells in the dura mater thereby identifying them as mast cells. In addition, because these cells were highly sensitive to compound 48/80 and were densely packed with granules of a consistent density, they were identified specifically as 'connective tissue' mast cells. Other types of mast cells, i.e. 'mucosal' or 'neurolipomastocytes', were not present in the rat dura mater. 5-HT immunohistochemistry was the best technique for demonstrating that there were populations of mast cells, one associated with each of the two layers of dura. Although shaped differently the type of mast cell in each layer was the same. It was observed that mast cell shape is dependent on the contiguity, density and orientation of its surrounding elements, not its type. In general, mast cells in the outer layer were aligned parallel to the middle meningeal artery and those in the inner layer were parallel to trigeminal nerve branches that coursed obliquely across the middle meningeal artery. Examination of cross sections of dura revealed that most mast cells also were aligned at the interface between the two dural layers. The linear orientation of mast cells in two planes of each layer suggests a programmed lamellar seeding of these cells during development of the dura. This study also demonstrated that the majority of dural mast cells were more closely related to other connective tissue elements than to blood vessels and nerves. These results (1) are compatible with the suggestion that dural mast cells play a non-obligatory role in the neuroinflammatory response, (2) leave open to question the role of the dural mast cell in headache or the regulation of blood flow, and (3) support evidence that dural mast cells play an important role in connective tissue related functions, e.g. development, inflammatory response to injury and wound repair. PMID- 1869886 TI - Periaxonal ensheathment of lobster giant nerve fibres as revealed by freeze fracture and lanthanum penetration. AB - Sheath structure and permeability have been studied in the nerve fibres of lobster (Panulirus argus) walking limbs, in particular the individually ensheathed larger giant fibres, 100-150 microns in diameter, of which there are five or six in a peripheral bundle. They are easily distinguished and can be separated from neighbouring fibre bundles in which smaller giant axons (65-80 microns diameter) and many axons of much smaller diameter (5-15 microns) are ensheathed together. Each of the larger giant axons is enveloped by a Schwann cell layer outside of which is a multilayered sheath consisting of one-cell thick belts of flattened cells and interleaved zones of collagen fibrils and extracellular matrix. The cells in each belt lack basal lamina and, after freeze fracture, as well as in thin sections, exhibit intercellular gap junctions and incomplete, fascia type, tight junctions; their most striking aspect is an exceedingly large number of exo-endocytic profiles. Permeability to lanthanum chloride in the bathing medium studied before or during fixation both in intact nerves and in nerves with surgically breached (slit) epineurium showed penetration of lanthanum tracer between the cells around the giant fibres, but the electron-dense tracer was excluded from the Schwann cell layer and the periaxonal space unless the epineurium had been slit. The extent of lanthanum diffusion was evaluated by transmission electron microscopy of thin sections and confirmed by X-ray microanalysis (EDAX) of comparable selected areas in such sections. The results indicate structural similarities but distinct permeability differences between the multilayered sheath surrounding the lobster giant axons and the vertebrate nerve perineurium. Other ultrastructural details provided by the freeze-fracture replicas concern the distribution of intramembrane particles in the axolemma and the Schwann and sheath cell membranes. PMID- 1869887 TI - Large GABA cells of chick ectostriatum: anatomical evidence suggesting a double GABAergic disinhibitory mechanism. An electron microscopic immunocytochemical study. AB - In an extension of our previous light microscopic observations, a type of neuron which shows GABA-like immunoreactivity was identified and described in the ectostriatal core of young domestic chicks, using pre- and postembedding electron microscopic immunocytochemistry. Large GABA immunopositive (GABA+) cells are characterized by an ovoidal or polygonal soma of 12-16 micron diameter, uniformly distributed nuclear chromatin, a prominent Golgi apparatus and an abundance of rough endoplasmic reticulum. In addition to axodendritic terminals, large GABA neurons receive numerous axosomatic synapses of both symmetrical and asymmetrical types covering a substantial part of their perikaryal surface. Axosomatic terminals with symmetrical junctions are usually immunoreactive to GABA whereas the boutons with asymmetrical synaptic specialization are immunonegative. GABA+ boutons also synapse with dendritic spine necks presumably belonging to projection neurons. These terminals usually contain loosely packed synaptic vesicles without any marked accumulation near the synaptic cleft. Large GABA+ terminals with densely packed vesicles were found to synapse with axon hillocks. Based on known descriptions of ectostriatal cytoarchitecture and synaptology, it is suggested that the GABA+ cells of chick ectostriatum represent inhibitory interneurons which may be equivalent to GABAergic non-pyramidal neuronal types of mammalian visual cortex. GABA+ axosomatic synapses afferent to large GABA cells are likely to form the structural basis for a disinhibitory mechanism in the avian ectostriatum. PMID- 1869888 TI - Trends in the pathophysiology and pharmacotherapy of spasticity. AB - Spasticity develops after supraspinal or spinal lesions of descending motor systems, with obligate involvement of the corticospinal tract. Spasticity is characterized by an increase in muscle tone, which, in contrast to many other types of enhanced muscle tone, shows a marked velocity-dependent increase when the muscle is passively stretched. The pathophysiological mechanisms underlying this spastic muscle tone remain obscure. Three major causes are currently considered possible: (1) changes in the excitability of spinal interneurones; (2) receptor hypersensitivity; (3) formation of new synapses by sprouting. The latter mechanism could account for the long time course over which spastic muscle tone develops in hemiplegic or paraplegic patients, but there is no experimental evidence for this hypothesis. The electromyographic (EMG) gait analysis of patients with spasticity has thrown doubt on the common belief that the velocity dependent increase in spastic muscle tone is evoked by stretch reflex activity and has led to the idea that spastic muscle tone resides in the muscle fibres themselves. While such a mechanism may contribute to the slowness of active movements in spastic patients, recent experiments on patients with spastic arm paresis have confirmed the classical view that the spastic muscle tone is related to the EMG activity evoked in the passively stretched muscle. This pathological EMG activity is seen during the entire range of the dynamic phase of the stretch, during which a normal muscle exhibits only an early, phasic burst at the highest stretch velocities employed. For the pharmacological treatment of spasticity, substances with different central or peripheral actions are available. Their assumed receptor actions are described, together with their main indications and side-effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869889 TI - How to identify psychogenic disorders of stance and gait. A video study in 37 patients. AB - Thirty-seven patients with psychogenic disorders of stance and gait were clinically evaluated, recorded on video, and analysed with regard to clinical phenomenology. Characteristic, suggestive and unspecific features were identified. Six characteristic features proved most valuable for diagnosis of psychogenesis, as they occurred alone or in combination in 97% of patients: (1) momentary fluctuations of stance and gait, often in response to suggestion; (2) excessive slowness or hesitation of locomotion incompatible with neurological disease; (3) "psychogenic" Romberg test with a build-up of sway amplitudes after a silent latency or with improvement by distraction; (4) uneconomic postures with wastage of muscular energy; (5) the "walking on ice" gait pattern, which is characterized by small cautious steps with fixed ankle joints; (6) sudden buckling of the knees, usually without falls. Seventy-three percent of patients had additional suggestive features. Classification into characteristic subtypes was not found useful because predominant features varied from patient to patient and occurred in various combinations. Factitious impairment of stance and gait was studied in 13 healthy drama students. Simulated gait dysfunction appeared less conspicuous and more difficult to diagnose than the clinical psychogenic disorders. PMID- 1869890 TI - Intrafamilial phenotype variation in Friedreich's disease: possible exceptions to diagnostic criteria. AB - Three families are described which include members with "typical" Friedreich's disease (FD) and others who are ataxic but do not satisfy all the diagnostic criteria for that disease. In family A two patients have an early-onset, rapidly progressive FD, while two others have a late-onset, more benign form. In families B and C one member has "typical" FD, and another has a similar ataxic syndrome, except for preservation of knee jerks. Laboratory evaluation is consistent with the diagnosis of FD in all cases. FD diagnosis appears justified in secondary cases with late onset or preserved tendon reflexes, provided that the index case fulfils all diagnostic criteria. Whether the diagnosis of FD is tenable in sporadic "atypical" cases remains to be seen. Echocardiographic and neurophysiological examination may be valuable in classifying such cases. PMID- 1869891 TI - Striatopallidonigral degeneration in Pick's disease: a clinicopathological study of 41 cases. AB - The frequency and degree of stiatopallidonigral (SPN) degeneration were examined in 41 autopsy cases of Pick's disease. Based on the degree of SPN degeneration, these cases were arranged into four groups: 1) group I (severely degenerate; 19.5%), 2) group II (moderately degenerate; 22.0%), 3) group III (mildly degenerate; 36.5%), and 4) group IV (non-degenerate; 22.0%). 17 of the 41 cases had a definite (moderate to severe) SPN degeneration. The striatum, especially the caudate nucleus, was most frequently and most severely affected, while the internal segment of the globus pallidus was least frequently and least severely affected. In general, the oral portions of the SPN nuclei were more severely involved. In addition, in the putamen and globus pallidus the dorsomedial portions adjacent to the internal capsule were apt to be affected more markedly than the other portions. In the substantia nigra the degeneration tended to be more predominant in the pars reticulata than in the pars compacta, although both were usually involved. In addition, the medial to central portions of the substantia nigra were more vulnerable. In comparing the severely and moderately degenerate groups (groups I and II) with the mildly and non degenerate groups (groups III and IV), the former had more female cases, longer duration of illness, and more third-stage cases. In addition, the former contained more cases with lower brain weight and (predominant) frontal atrophy type, and more atypical cases without Pick bodies, or with symmetrical pyramidal tract degeneration or with combined traumatic lesions. It is notable that in all cases with definite SPN degeneration no extrapyramidal involuntary movements had been detected. PMID- 1869893 TI - Sarcoid neuropathy. AB - In a case of subacute sensory and motor polyneuropathy associated with sarcoidosis, multiple epineurial and endoneurial granulomas were demonstrated in a sural nerve. Neighbouring nerve fibres were displaced by the granulomas and some were undergoing axonal degeneration. Ultrastructural and teased fibre studies showed axonal atrophy and degeneration with secondary demyelination. Histochemical studies indicated the presence of HLA-DR antigen on epithelioid cells in the granulomas. A non-specific inflammatory process in the nerve does not cause significant primary demyelination. PMID- 1869892 TI - Somatosensory evoked potentials to median nerve stimulation after partial section of the corpus callosum. AB - Cortical somatosensory evoked potentials (SEPs) to electrical stimulation of the median nerve were studied in four patients with intractable epilepsy who had undergone callosotomy and in a patient with infarction in the corpus callosum in order to determine whether the corpus callosum was involved in the generation of ipsilateral frontal components. Both pre- and postoperative SEPs were recorded in three of four epileptic patients. There were no significant differences in the latencies and amplitudes of the bilateral frontal components (P20, N26) between pre- and postoperative recordings. Furthermore, irrespective of the extent of the section or lesion in the corpus callosum, the nature of the impairment and the existence of the disconnection syndrome, the SEP findings showed no significant differences compared with those of normal subjects. It thus appears unlikely that the ipsilateral SEP responses are transmitted from the contralateral hemisphere through at least the anterior portion of the corpus callosum. PMID- 1869894 TI - Immunohistology of temporal arteritis: phenotyping of infiltrating cells and deposits of complement components. AB - Deposition of complement factors, immunoglobulins and infiltrating cells was evaluated by immunohistochemical staining in 30 temporal artery biopsy specimens from patients suffering from temporal arteritis and/or polymyalgia rheumatica and in controls. In the temporal arteritis group infiltrating cells, classic complement, alternative complement and lytic complex activation were detected. In specimens from patients suffering from only polymyalgia rheumatica there was unexpected evidence of classic complement and lytic complex activation. We conclude that immuno-histochemistry provides support for the concept of temporal arteritis and polymyalgia being based on the same pathological process. PMID- 1869895 TI - The treatment of multiple intracranial tuberculous abscesses: a case report. AB - A Chinese female aged 2 years 8 months with tuberculous meningitis developed hydrocephalus requiring insertion of a ventriculoperitoneal shunt. After adequate anti-tuberculosis chemotherapy for 14 weeks, multiple intracranial tuberculous abscesses developed. The lesions increased in size and number accompanied by clinical deterioration. Repeated drainage operations were performed in view of the increased intracranial pressure. The child made a remarkable recovery after an initial stormy course. PMID- 1869896 TI - Molecular structure matching by simulated annealing. III. The incorporation of null correspondences into the matching problem. AB - This paper extends an application of the method of simulated annealing for molecular matching so that the best common subsets of atom positions can be identified. Null correspondences are introduced into the difference distance matrix to enable poorly matched positions to be ignored in minimizing the objective function. The efficiency of the algorithm in finding correct subsets is rigorously tested. PMID- 1869897 TI - Conformation of receptor-associated PGI2: an investigation by molecular modeling. AB - To elucidate the conformation of receptor-associated prostacyclin (PGI2), we first performed structure-activity correlation analysis of over 200 PGI2 analogues and derived from this analysis several crucial features pertaining to structural requirements for PGI2 activity [Ah-lim Tsai and Kenneth K. Wu, Eicosanoids, 2 (1989) 131-143]. These structural features proved to be useful guidelines for selecting 'model molecules' for further investigations by molecular mechanics. By properly selecting four analogues with either rigid or uniquely oriented alpha-side chain structure for geometric fitting, we succeeded in maximally minimizing the degree of freedom of the carboxylate terminus of PGI2. We were able to define the spatial relationship among the four critical functional groups, i.e., C1-COOH, C6a-O, C11-OH and C15-OH. More information is needed, however, to define the geometry of the omega-side chain, particularly for the moiety beyond C15. Nevertheless, results from structure-activity correlation analysis and molecular modeling provide useful information regarding the conformation of receptor-associated PGI2, which assumes an 'elongated' conformation instead of the traditional 'hairpin' structure. PMID- 1869899 TI - Do you believe in wavefunctions? PMID- 1869898 TI - Development of an automatic estimation system for both the partition coefficient and aqueous solubility. AB - A computer program has been developed for estimating both the partition coefficient between 1-octanol and water phases and the aqueous solubility from the structural formula. This system is an extended version of a previously described program entitled CHEMICALC for the automatic estimation of the partition coefficient. The aqueous solubility is estimated via two pathways. The first is based on the linear relationship between logarithms of the aqueous solubilities of 497 compounds and their estimated 1-octanol/water partition coefficients. In the second, combined handling of two available group contribution methods of Irmann [Chem. Ing. Tech., 37 (1965) 789] and Wakita et al. [Chem. Pharm. Bull., 34 (1986) 4663] is adopted according to compound type. Some revisions and extensions of the methods for estimating the aqueous solubility have been made in both pathways, and the accuracy of the estimated aqueous solubilities for 497 compounds is discussed. PMID- 1869901 TI - CICIAMS XIV World Congress New York. Perennial ethical and moral values in a changing society. PMID- 1869900 TI - A supermolecule study of the effect of hydration on the conformational behaviour of leucine-enkephalin. AB - A theoretical conformational study was performed on leu-enkephalin in its zwitterionic form, both in vacuo and in the presence of a number, n, of up to 13 water molecules saturating its first hydration shell. The intramolecular energy of enkephalin as well as the intermolecular enkephalin-water and water-water interaction energies were computed with the SIBFA procedure (Sum of Interactions Between Fragments Ab initio computed), which uses additive ab initio multipole systematics and analytical formulas grounded on ab initio SCF computations. Energy minimizations were performed with a polyvalent minimizer, Merlin, with which three distinct derivative and three distinct nonderivative minimizers can be activated in a sequential fashion. Eight different candidate conformations of enkephalin were used as starting points. These conformations are either those found in distinct X-ray structures, or those proposed on the basis of theoretical computations by other authors. In the absence of hydration, they converged towards distinct folded energy-minima, the best four ones being separated by an energy gap of 8.7 kcal/mol. In marked contrast, with up to n = 13, the energetical separation between the six best conformers narrowed down to congruent to 4 kcal/mol. They can be characterized by: (a) either a direct or a water mediated ammonium-carboxylate interaction; b) either a close proximity (as in morphine) or a large separation between the aromatic rings of Tyr and Phe (intercenter separations of congruent to 4.5 A and congruent to 10.5 A, respectively), with each of the four mutual combinations of (a) and (b) being represented. PMID- 1869902 TI - National Conference Walsingham October 1990. PMID- 1869903 TI - Electrophysiological evidence for a direct projection of direction-sensitive retinal ganglion cells to the turtle's accessory optic system. AB - 1. The direct retinal input pathway to the basal optic nucleus (BON), the primary nucleus of the turtle accessory optic system, was characterized physiologically. We tested the hypothesis that directional information encoded in retinal ganglion cells can influence the BON via a direct pathway. Using an in vitro whole-brain, eyes-attached preparation, we demonstrated the directness of this pathway by 1) antidromic activation of retinal ganglion cells from the contralateral BON and 2) orthodromic activation of the BON from the contralateral optic nerve. 2. Of 72 physiologically classified retinal ganglion cells, 9 could be antidromically activated from the contralateral BON with low current (less than 200 micro A). Eight of these cells were direction-sensitive (DS). The ninth cell did not respond to visual stimulus movement. The antidromic latencies ranged from 2.2 to 6.1 ms with a mean of 3.8 ms. These latencies were quite consistent for each cell, having an average SD of 0.08 ms. Moreover, consistent responses could always be recorded at stimulation rates up to 100 Hz. 3. With current stimulation of the contralateral optic nerve, the orthodromic conduction latency of 17 BON single units ranged from 2.5 to 6.6 ms with a mean of 4.6 ms. These latencies were more variable for an individual cell, having an average SD of 0.3 ms. Responses to individual current pulses could never be consistently evoked at stimulation rates greater than 40 Hz. 4. DS responses were recorded in BON single units after the removal of the dorsal midbrain, including the optic tectum and pretectum as well as the telencephalon. Three of these cells were activated orthodromically by current stimulation delivered to the contralateral optic nerve. Thus directional information reaches the BON via a direct projection from the contralateral retina. 5. Visual response properties of DS retinal ganglion cells were compared with those of BON cells to examine the transformations that take place in the brain stem. Applying a limacon model to the responses of both DS retinal ganglion cells and BON cells revealed that both types of cells have very similar direction tuning. However, the distribution of maximally responsive directions in the retina may differ from that of the BON. 6. Because DS retinal ganglion cells project directly to the BON, and because BON cells lose their direction sensitivity after retinal application of GABA antagonists, we conclude that the BON receives essential directional information directly from DS retinal ganglion cells. This directional information in the BON may represent a retinal slip error signal necessary for retinal image stabilization. PMID- 1869904 TI - Convergence of phrenic and cardiopulmonary spinal afferent information on cervical and thoracic spinothalamic tract neurons in the monkey: implications for referred pain from the diaphragm and heart. AB - 1. Spinothalamic tract (STT) neurons in the C3-T6 spinal segments were studied for their responses to stimulation of phrenic and cardiopulmonary spinal afferent fibers. A total of 142 STT neurons were studied in 44 anesthetized, paralyzed monkeys (Macaca fascicularis). All neurons were antidromically activated from the ventroposterolateral nucleus and/or medial thalamus. 2. Electrical stimulation of phrenic afferent fibers (PHR) excited 43/58 (74%), inhibited 2/58 (3%), and did not affect 13/58 (13%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of PHR than were neurons with somatic fields confined to the distal limb. Mechanical stimulation of PHR by probing the exposed diaphragm excited 11/22 (50%), inhibited 3/22 (14%), and did not affect 8/22 (36%) cervical STT neurons. 3. The technique of minimum afferent conduction velocity (MACV) was used to obtain information about the identity of the PHR that excited 35 cervical STT neurons. Evidence was obtained for excitation of these neurons by group II and III PHR. The mean +/- SE MACV for all neurons was 14 +/- 2 m/s. 4. Electrical stimulation of cardiopulmonary spinal afferent fibers excited 41/57 (72%), inhibited 8/57 (14%), and did not affect 8/57 (14%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of cardiopulmonary spinal afferents than were neurons with somatic fields confined to the distal limb. 5. Excitatory convergence of PHR and cardiopulmonary spinal afferent input was observed for 36/57 (63%) cervical STT neurons. 6. Electrical stimulation of PHR excited 36/84 (43%), inhibited 25/84 (30%), and did not affect 23/84 (27%) of thoracic STT neurons. All of these neurons received excitatory cardiopulmonary spinal afferent input. 7. Neurons were more likely to be excited by electrical stimulation of PHR if they were located in C3-C6 spinal segments. Furthermore, the net excitatory effect of PHR input decreased in more caudal segments, such that thoracic STT neurons were weakly excited relative to cervical STT neurons. 8. We conclude that cervical STT neurons with excitatory somatic fields that include or are restricted to proximal sites are excited by electrical or mechanical stimulation of PHR. Those effects demonstrate a physiological substrate for pain referred from the diaphragm to the shoulder in patients with pleural effusions or subphrenic abscesses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1869905 TI - Receptive properties of sacral primary afferent neurons supplying the colon. AB - 1. Conscious perception of noxious and innocuous distension of the colon as well as the reflex control of anal continence and defecation largely depend on an intact sacral primary afferent innervation. Here we have studied the functional properties of these visceral primary afferent neurons in the dorsal root S2 in 17 cats. Single fibers projecting into the pelvic nerve were identified electrically and studied with innocuous and noxious mechanical stimulation of colon and anal canal. 2. A total of 59 units responding to one of these stimuli were investigated and they could be separated into two subpopulations of afferents. Thirty-six fibers were reproducibly excited by distension of the colon, but not by mechanical stimulation of the anal canal. They were thin myelinated or unmyelinated fibers with a median conduction velocity of 3.2 m/s. The remaining 23 units had receptive fields in the mucosa of the anal canal and responded readily to an innocuous proximodistal shearing stimulus, but not to distension stimuli applied to the same area. All, but two of these afferents were thin myelinated with a median conduction velocity of 7.7 m/s, which was significantly different from the conduction velocity of afferent neurons responding to distension of the colon. 3. Units responding to distension of the colon had thresholds in the innocuous range of the intracolonic pressure. Receptors that were activated only by noxious intraluminal pressure were absent. On the basis of their response to supramaximal isotonic distension, colonic afferents could be subclassified as phasic (n = 17) or tonic (n = 19) units. Phasic afferents were only transiently excited during filling or emptying of the colon, whereas tonic afferents discharged throughout the distension. The two populations had also significantly different median conduction velocities of 8.0 (n = 16) and 1.7 (n = 15) m/s, respectively. 4. Stimulation response functions were evaluated for 12 tonic afferents. All units encoded an increase of intracolonic pressure by the intensity of their discharge frequency. Increases of intracolonic pressure produced significantly higher discharge frequencies from unmyelinated than from thin myelinated afferents. 5. In three animals the percentage of unmyelinated fibers responding to mechanical stimulation of colon and anal canal was determined. Out of 213 electrically identified unmyelinated units projecting into the pelvic nerve, only 11 (5.2%) were excited. Thus, acute innocuous and noxious mechanical stimuli of the large intestine do not appear to be the adequate stimulus for the large majority of unmyelinated pelvic afferents. 6. In conclusion, distension of the colon and mechanical stimulation of the anal canal activates distinct populations of primary afferent neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1869906 TI - Area 18 corticotectal cells: response properties and identification of sustaining geniculate inputs. AB - 1. We examined the response properties and geniculate inputs of 35 antidromically identified corticotectal (CT) cells within area 18 of the paralyzed, anesthetized cat. Twenty-three were either standard complex or hypercomplex, 11 were special complex, and 1 was simple. 2. The response properties of CT cells in area 18 were in general quite similar to those examined in a previous study of area 17 CT cells, including similar proportions of standard and special complex CT cells, virtually identical length-response functions, and similar orientation and direction tuning. 3. Area 18 CT cells are rapidly conducting. They are considerably faster than area 17 CT cells. 4. We investigated the composition of thalamic inputs to CT cells by reversibly inactivating a portion of layer A and/or the C layers of the dorsal lateral geniculate nucleus with injections of cobaltous chloride. Blocking layer A strongly attenuated the visual responsiveness of about half of the cells tested. Blocking the C layers alone generally had only moderate effects, but simultaneous blockade of layer A and the C layers demonstrated a substantial C-layer input to many cells. Unlike area 17 in which there is a strong correlation between CT cell class and dependence on layer A, no single receptive-field parameter nor set of parameters was correlated with dependence on layer A. However, cells least affected by simultaneous blockade of layer A and the C layers were special complex, suggesting that, as in area 17, area 18 special complex CT cells integrate more geniculate inputs than standard complex CT cells. 5. We propose that the similarities of response properties of area 17 and area 18 CT cells results from their participation in similar interlaminar columnar circuits and that differences in the patterns of geniculate control reflect differences in the global patterns of geniculate inputs to these two areas. PMID- 1869907 TI - Organization of gustatory sensitivities in hamster superior laryngeal nerve fibers. AB - 1. Mammalian taste receptors are distributed within several distinct subpopulations, innervated by branches of cranial nerves VII, IX, and X. Most gustatory electrophysiology has focused on input from the fungiform papillae on the anterior portion of the tongue, carried by the chorda tympani branch of the VIIth nerve. However, laryngeal taste buds in the hamster are as numerous as those in the fungiform papillae. Gustatory fibers in the hamster's chorda tympani and glossopharyngeal nerves have been well characterized. In comparison with these taste fibers, much less is known about the chemical sensitivities of fibers innervating laryngeal taste buds. 2. Action potentials were recorded from 65 individual fibers in the superior laryngeal nerve (SLN) of the hamster. Stimuli were distilled H2O and five concentrations each of sucrose, NaCl, HCl, and quinine hydrochloride (QHCl). All stimuli except the NaCl series were made in physiological saline (0.154 M NaCl) and were delivered from the laryngeal side of the epiglottis via a tracheal cannula. Responses were quantified as the number of impulses in 10 s minus the responses in the preceding 10 s of baseline activity during a rinse with physiological saline. 3. Distilled H2O, HCl, and NaCl were by far the most excitatory stimuli, with mean responses across all cells 5-10 times greater than those evoked by sucrose or QHCl. The order of effectiveness of the strongest concentrations of the stimuli was H2O greater than 0.03 M HCl greater than 1.0 M NaCl much greater than 0.03 M QHCl greater than 1.0 M sucrose. 4. The mean concentration-response function for NaCl was U shaped, with the greatest number of impulses to distilled H2O and 1.0 M NaCl. The responses diminished as the concentrations approached physiological levels (0.154 M NaCl), where there was no response, and increased as NaCl concentration rose above this level. Increasing concentrations of HCl above 0.0003 M elicited increasing responses in these fibers. 5. The mean time course of the responses to distilled H2O and to hypotonic NaCl solutions (0.01 and 0.03 M) peaked in the first few seconds and then declined slowly. This was distinct from the time course of the responses to hypertonic NaCl concentrations (0.3 and 1.0 M), which increased gradually throughout the 10-s response period. Responses to HCl peaked in the initial second and then decayed rapidly to a slowly declining plateau. These distinctively different time courses suggest different receptor mechanisms for water, salt, and acid stimuli. 6. The across-fiber pattern of the responses to hypotonic NaCl solutions correlated strongly to that elicited by distilled H2O.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1869908 TI - Selectivity for relative motion in the monkey superior colliculus. AB - 1. Cells in the superficial layers of the colliculus were studied in immobilized monkeys anesthetized with nitrous oxide. We examined sensitivity to the relative motion between two stimuli: a small target in a cell's receptive field and a large random-dot background pattern that filled most of the visual field outside the receptive field. 2. Most cells were nonselective for either target direction or speed when the background pattern was stationary but were selective for both direction and speed relative to a moving background. Selectivity for relative motion was independent of the absolute direction and speed of both target and background. When both moved at the same speed in the same direction, the response evoked by the target was strongly suppressed. Changing the background direction relative to the target reduced the suppression; suppression was minimal when the two moved in opposite directions. Selectivity for relative direction was broad: the average tuning width at half-amplitude was 136 degrees. When target and background moved in the same direction, increasing or decreasing background speed relative to the target likewise reduced suppression. Average tuning width for relative speed was 1.4 log units. 3. Selectivity for relative motion was a global phenomenon. Suppression was present even when the background pattern was excluded from a region 10 times the receptive-field diameter. However, suppression gradually diminished with increasing distance between the receptive field and the background pattern. 4. Relative motion selectivity was most common in the deeper part of the superficial layers. Ninety percent of the cells below the middle of the stratum griseum superficiale were selective for relative direction, whereas above this level only 45% of the cells were. 5. Cells in the magnocellular and parvocellular layers of the lateral geniculate nucleus did not show selectivity for relative direction. 6. We suggest that the lower one-half of the superficial grey layer and the stratum opticum together constitute a subdivision of the superior colliculus that is specialized to detect strong discontinuities in relative motion. Descending input by way of the corticotectal tract is probably essential for the detection process. the projections from this tectal motion zone to the pulvinar, and from there to prestriate cortex, may provide a feedback pathway through which motion discontinuities such as occur at dynamic occlusion boundaries can influence local feature detection by cortical neurons. PMID- 1869909 TI - Spatial distribution of recurrent inhibitory synapses on spinal motoneurons in the cat. AB - 1. Intracellular staining of Renshaw cells and alpha motoneurons was used to determine the spatial distribution of recurrent inhibitory synapses on spinal motoneurons in the cat. In each experiment, a Renshaw cell and one or more possible target motoneurons were labeled with horseradish peroxidase after physiological identification. 2. Paris of labeled neurons were reconstructed and measured at the light microscopic level. As defined by light microscopy, presumed synaptic contacts between nine Renshaw cells and 10 postsynaptic motoneurons were observed. On average, each Renshaw cell made three synaptic contacts (range 1-9) on each motoneuron. 3. Electron microscopic confirmation of several presumed contacts provided evidence that the appositions identified by light microscopic criteria are genuine contacts between Renshaw cell boutons and the labeled motoneuron. 4. All of the identified synapses observed in these experiments were located on motoneuron dendrites, between 65 and 706 microns from the soma. Use of a simplified cable model indicated that the synapses are electrotonically close to the soma, the average location being approximately 0.25 length constants from the soma (range 0.04-0.82 lambda). 5. These observations provide direct evidence to support the hypothesis that Renshaw cell synapses on motoneurons are located on the dendrites and not on the cell body (whereas reciprocal inhibitory synapses, from Ia inhibitory interneurons, are predominantly located on the soma). The functional significance of the observed distribution of Renshaw inhibitory synapses is discussed. One possibility is that the recurrent inhibitory pathway selectively inhibits particular dendritic inputs. PMID- 1869910 TI - Delayed excitatory connections in the flight system of the locust. AB - 1. Synaptic interactions between identified neurons in the flight system of the locust were investigated by the use of standard intracellular recording and staining techniques. The intent was to determine the distribution and functional significance of delayed excitatory connections, which have been previously described. 2. For one inhibitory connection it was demonstrated that subthreshold depolarization of the presynaptic neuron was sufficient to cause release of transmitter at the synapse. This established the existence of graded interactions between spiking flight neurons. 3. Three inhibitory interneurons were found to cause delayed excitatory responses in several other neurons. Often these were coupled with direct inhibitory connections between the same pre- and postsynaptic neurons, resulting in an inhibitory/excitatory (I/E) postsynaptic potential (PSP). The two phases of this PSP were variable. 4. Delayed excitatory connections appeared powerful while the flight system was inactive. However, these connections were disabled during flight rhythms at the phase when the presynaptic neuron was depolarized and firing action potentials. This was likely to be due to the nature of the disynaptic disinhibitory interaction being via (an) intervening neuron(s) with oscillating membrane potentials and thresholds for release of transmitter. 5. Thus connections demonstrated when flight rhythms were not expressed changed their character during flight rhythms. The delayed excitatory connections in this system probably reflect complex circuits of inhibition mediated by graded interactions and have little functional significance as phenomena in their own right. PMID- 1869911 TI - Eye movement responses to linear head motion in the squirrel monkey. I. Basic characteristics. AB - 1. The purpose of this study was to quantify the response characteristics of eye movements produced by linear head oscillations in the dark (the linear vestibuloocular reflex, or LVOR). Horizontal, vertical, and torsional eye movements were measured in adult squirrel monkeys by the use of a dual scleral search-coil technique during linear oscillations (0.5, 1.5, and 5.0 Hz, 0.36 g peak acceleration) along the animals' interaural (IA), dorsoventral (DV), and nasooccipital (NO) axes. 2. Two LVOR responses, horizontal eye movements during IA-axis translation and vertical eye movements during DV-axis motion, were in a compensatory direction for head translation. Response amplitudes increased as frequency increased, whereas phase typically showed a lead. 3. Two other LVORs, torsional responses during IA-axis translation (all frequencies) and vertical responses during NO-axis oscillations (0.5 Hz), behaved differently. These two LVORs cannot be functionally compensatory for head translation because they degrade fixation on targets, and therefore image stability, by rotating the eyes off target (NO-vertical) or torting the eyes relative to the visual world (IA torsional). Responses to NO-axis motion at frequencies greater than 0.5 Hz depended on initial eye position and fixation distance and are described in the companion paper. 4. The effect of head orientation on the LVOR was assessed by testing four head positions in 90 degrees steps around the axis of head motion for each of the three axes of translation. This was done, first, to determine whether the LVORs are responses to the "swinging vector" of gravitoinertial force during linear head motion or to head translation; and second, to quantify potential effects of static head (otolith) orientation on the LVORs. Results showed no systematic effects of head orientation on LVOR responses in the frequency bandwidth studied. This indicates that the LVORs are dependent on the direction of linear motion relative to the head (and otolith organs) but not on the swinging vector of gravitoinertial force, and that the LVORs are uninfluenced by static orientation of the head and reloading of the otoliths. PMID- 1869912 TI - Eye movement responses to linear head motion in the squirrel monkey. II. Visual vestibular interactions and kinematic considerations. AB - 1. Horizontal, vertical, and torsional eye movements were recorded (search coil technique) from five squirrel monkeys during horizontal linear oscillations at 0.5, 1.5, and 5.0 Hz, 0.36 g peak acceleration. Monkeys were positioned to produce linear motion in their nasooccipital (NO), interaural (IA), and dorsoventral (DV) axes. Responses of the linear vestibuloocular reflex (LVOR) were recorded in darkness and in the light with the subjects viewing a head-fixed field 22 or 9.2 cm from the eye. The latter condition provided a measure of "visual suppression" of the LVOR (VSLVOR). Responses were also recorded while monkeys viewed earth-fixed targets, which allowed visual enhancement of the LVOR (VLVOR). Vergence angle was recorded in two monkeys to assess directly the point of binocular fixation in space during linear motion. 2. Two LVOR response types, vertical responses during 0.5-Hz NO-axis translation (NO-vertical) and torsional responses at all frequencies during IA-axis oscillation (IA-torsional) could not be compensatory reflexes for head translation because they either move the eye off target (NO-vertical) or tort the eye relative to the visual world (IA torsional), thereby degrading visual image stability. 3. Other response types are considered compensatory because they help maintain ocular fixation in space during linear head translation. These include horizontal responses to IA-axis motion (IA-horizontal), vertical responses to DV-axis translation (DV-vertical), and both horizontal and vertical responses to NO-axis oscillation (1.5 and 5 Hz). Observations focus on responses to 5-Hz oscillations, in which visual inputs are essentially ineffective in modifying the LVOR. 4. The kinematics of perfect ocular compensation during head translation indicate that the ideal ocular response is governed by the motion of the eye relative to target position. Relevant variables include target distance, which is crucial for all axes of motion, and target eccentricity, which is important only for head motion roughly parallel to the target (NO-axis translation). Findings are compatible with predictions based on ideal kinematics. However, it is the point of binocular fixation in space, not actual target position, that governs LVOR behavior. 5. The IA-horizontal and DV-vertical LVOR is in response to head motion roughly orthogonal to the line of sight. Responses under all stimulus conditions (LVOR, VSLVOR, and VLVOR) behaved similarly at 5 Hz, and were modulated linearly with vergence [in meter angles (MA), the reciprocal of binocular fixation distance].(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1869913 TI - Physiology and topography of neurons with multipeaked tuning curves in cat primary auditory cortex. AB - 1. The physiology and topography of single neuron responses along the isofrequency domain of the middle- and high-frequency portions [characteristic frequencies (CFs) greater than 4 kHz] of the primary auditory cortex (AI) were investigated in the barbiturate-anesthetized cat. Single neurons were recorded at several locations along the extent of isofrequency contours, defined from initial multiple-unit mapping. For each neuron a high-resolution excitatory tuning curve was determined, and for some neurons high-resolution two-tone tuning curves were recorded to measure inhibitory/suppressive areas. 2. A physiologically distinct population of neurons was found in the dorsal part of cat AI. These neurons exhibited two or three distinct excitatory frequency ranges, whereas most neurons in AI responded with excitation to a single narrow frequency range. These were called multipeaked neurons because of the shape of their tuning curves. At frequencies between the excitatory regions, the multipeaked neurons were inhibited or unresponsive. 3. Multipeaked neurons exhibited several distinct threshold minima in their frequency tuning curves. Most of the multipeaked neurons (88%) displayed two frequency minima, whereas the rest exhibited three minima. 4. The frequency separation between threshold minima was less than 1 octave in 71% of the double-peaked neurons recorded. Occasionally, the frequency peaks of these neurons closely corresponded to a response to second and third harmonics without a response to the fundamental frequency. 5. Multipeaked neurons exhibited a wide range of total bandwidths (highest excitatory frequency minus lowest excitatory frequency expressed in octaves). Bandwidths of the isolated peaks within the same neuron were also quite variable. 6. Response latencies to tones with frequencies within each peak of a multipeaked neuron could vary considerably. In 71% (17) of the neurons, tones corresponding to the high frequency peak (CFh) elicited a longer response latency (greater than 4 ms) than those corresponding to the low-frequency peak (CF1). 7. Inhibitory/suppressive bands, as demonstrated with a two-tone paradigm, were often present between the peaks. Typically, neurons with excitatory peaks of similar response latencies showed an inhibitory band located between the peaks. 8. Ninety percent of the topographically localized multipeaked neurons were in the dorsal part of AI (greater than 1 mm dorsal to the maximum in the sharpness-of-tuning map). Although these neurons were restricted to dorsal AI, only 35% of neurons in this region were multipeaked. 9. Multipeaked neurons could show decreased response latencies and thresholds to two-tone combinations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1869914 TI - Cortical organization of language. AB - Recent data obtained by various methods of clinical investigations suggest an organization of language in the human brain involving compartmentalization into separate systems subserving different language functions. Each system includes multiple essential areas localized in the frontal and temporoparietal cortex of the dominant hemisphere, as well as widely dispersed neurons. All components of a system are activated in parallel, possibly by ascending thalamocortical circuits. The features peculiar to cerebral language organization include not only the lateralization of essential areas to one hemisphere, but also a substantial variance in the individual patterns of localization within that hemisphere, a variance that in part relates to individual differences in verbal skills. PMID- 1869915 TI - Mineralocorticoid hormones suppress serotonin-induced hyperpolarization of rat hippocampal CA1 neurons. AB - Pyramidal neurons in the rat CA1 hippocampal area contain intracellular mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) to which the adrenal hormone corticosterone can bind with differential affinity. The pyramidal neurons also have high amounts of 5-HT1a receptors, which mediate a membrane hyperpolarization. With intracellular recording in vitro, we found that selective occupation of MRs suppresses the 5-HT-induced hyperpolarization of CA1 pyramidal neurons. The suppression of 5-HT responses was observed 1-4 hr after a brief (20 min) application of the steroids. Binding properties of the 5-HT1a receptor were not significantly affected by in vitro steroid application. Furthermore, responses to the GABAB agonist baclofen were not changed after treatment with MR ligands, implying that the K+ conductance to which both GABAB and 5-HT1a receptors are linked is also no target for the steroid action. The MR-mediated effect on 5-HT responsiveness potentially enhances cellular activity. Because activation of GRs was previously found to suppress norepinephrine-induced excitability in the same neurons, the data support the concept that cellular homeostasis in the hippocampus is under control of corticosterone via coordinative, antagonistic MR- and GR-mediated events. PMID- 1869916 TI - The Lurcher cerebellar mutant phenotype is not expressed on a staggerer mutant background. AB - The hierarchy of the various processes responsible for the development of the complex, elaborated Purkinje cell can be examined by taking advantage of a series of spontaneous mutations that affect cerebellar development in the mouse. This study uses double mutants containing genes for two separate hereditary cerebellar mutations that have been shown to act intrinsically in Purkinje cells in order to investigate the time course and modes of action of these mutations. Lurcher mice show 100% degeneration of Purkinje cells, starting during the second postnatal week, while staggerer mice show reduced numbers of Purkinje cells in a distinctive mediolateral distribution from the time of birth, with the remainder grossly stunted. When these mutations are combined genetically, mice shown by progeny tests to harbor both staggerer and Lurcher genotypes exhibit staggerer like behavior and overall cerebellar morphology; they also do not lose 100% of their Purkinje cells, as Lurcher mutants would otherwise do. Instead, they show a characteristic staggerer cerebellar pathology. We conclude that the intrinsic action of the staggerer gene in Purkinje cells occurs earlier in development than do effects of the Lurcher gene, and that the action of the staggerer gene prevents Purkinje cells from acquiring the characteristics required for the cytotoxic action of the Lurcher gene. PMID- 1869917 TI - Cloning and characterization of Ca(2+)-dependent and Ca(2+)-independent PKCs expressed in Aplysia sensory cells. AB - We isolated cDNA clones from an Aplysia sensory-cell library encoding two isoforms of protein kinase C (PKC). Several isozyme-specific regions are conserved in the Aplysia kinases, notably the variable regions V5 in the Ca(2+) dependent PKC (Apl I) and V1 in the Ca(2+)-independent PKC (Apl II). Neuronal proteins with the properties expected of these two isoforms can be identified with antibodies raised against peptides synthesized from the amino acid sequences deduced from the clones. Sacktor and Schwartz (1990) measured the proportion of kinase activity that can be translocated to membrane in Aplysia sensory neurons and ganglia by stimuli that produce the presynaptic facilitation underlying behavioral sensitization. Much less Apl I and Apl II are translocated, suggesting that still other isoforms of PKC exist in these cells. PMID- 1869918 TI - Locus coeruleus involvement in the learning of classically conditioned bradycardia. AB - Opioid agonists are known to inhibit the activity of locus coeruleus (LC) neurons. In this study, microinjections of the mu-opioid agonist [D-Ala2, N-Me Phe4, Gly5-ol]-enkephalin (DAMGO; 1.6 microM) bilaterally into the LC caused a significant impairment in the development of a heart-rate (HR) conditioned response (CR). The adverse effect of DAMGO on the HR CR could be reversed with naltrexone pretreatment. Microinjections of DAMGO into the periaqueductal gray, parabrachial nucleus, or fourth ventricle structures 1-2 mm away from the LC had no effects on the development of an HR CR. We conclude that central noradrenergic activity as mediated by the LC is critically involved in the learning and retention of conditioned cardiovascular responses. PMID- 1869919 TI - Chronic androgen treatment increases action potential duration in the electric organ of Sternopygus. AB - The quasi-sinusoidal electric organ discharge (EOD) of the weakly electric fish Sternopygus is involved in communication and orientation. Each monophasic pulse of the low-intensity EOD is a compound action potential (AP) from the simultaneously firing electrocytes of the electric organ. EOD frequency is lower and EOD pulse duration longer in sexually mature males than in sexually mature females; exogenous androgen lowers EOD frequency and increases EOD pulse duration. In order to determine the contribution of single electrocyte spikes to the entire EOD pulse, APs were induced by intracellular current injection in single electrocytes of isolated pieces of electric organ. Each AP looks very similar to the externally recorded EOD pulses, and AP duration (APD) is significantly correlated with EOD pulse duration (r = 0.48; p less than 0.0005). The APD is slightly longer when compared to the EOD pulse duration, but this difference is likely due to the stimulation paradigm. Fish treated with dihydrotestosterone showed a decrease in EOD frequency, increase in EOD pulse duration, and corresponding increase in APD; control fish showed random, insignificant changes in EOD wave form and APD. Evidence presented here shows that changes in the passive membrane properties are unlikely to be responsible for the APD increase. The possibility is discussed that androgens act directly upon the electric organ, ultimately altering the ionic currents that produce the AP. PMID- 1869920 TI - Chronic testosterone treatment impairs vocal learning in male zebra finches during a restricted period of development. AB - To study the effects of chronic exposure to testosterone on song behavior development, we administered various amounts of testosterone to juvenile male zebra finches during different periods of song acquisition. We report that testosterone exposure during development profoundly impairs song learning in juvenile males. The effects of the hormone do not seem to be dose related but vary according to the period of life during which testosterone is administered. Exposure to testosterone starting before day 40 and lasting until adulthood decreases the number of syllables in the birds' repertoire and increases the number of phrases per bout of singing. In addition to these changes in the "syntactical" features of song, acoustic abnormalities are also present in the song syllables of males that begin to receive testosterone during the first month of life. Administration of testosterone during only the first 3 weeks of life produces acoustic abnormalities but has no effect on repertoire size or bout structure. Birds receiving the hormone between 20 and 40 d of age develop both acoustic abnormalities and a reduced repertoire size, but their song bouts contain a normal number of song phrases. Exposure to testosterone starting on day 40 produce no behavioral abnormalities. These results indicate that normal song development requires a period of low levels of circulating testosterone and also provide support for the idea that vocal learning entails a progressive sequence of events. PMID- 1869921 TI - Selective and divided attention during visual discriminations of shape, color, and speed: functional anatomy by positron emission tomography. AB - Positron emission tomography (PET) was used to identify the neural systems involved in discriminating the shape, color, and speed of a visual stimulus under conditions of selective and divided attention. Psychophysical evidence indicated that the sensitivity for discriminating subtle stimulus changes in a same different matching task was higher when subjects selectively attended to one attribute than when they divided attention among the attributes. PET measurements of brain activity indicated that modulations of extrastriate visual activity were primarily produced by task conditions of selective attention. Attention to speed activated a region in the left inferior parietal lobule. Attention to color activated a region in the collateral sulcus and dorsolateral occipital cortex, while attention to shape activated collateral sulcus (similarly to color), fusiform and parahippocampal gyri, and temporal cortex along the superior temporal sulcus. Outside the visual system, selective and divided attention activated nonoverlapping sets of brain regions. Selective conditions activated globus pallidus, caudate nucleus, lateral orbitofrontal cortex, posterior thalamus/colliculus, and insular-premotor regions, while the divided condition activated the anterior cingulate and dorsolateral prefrontal cortex. The results in the visual system demonstrate that selective attention to different features modulates activity in distinct regions of extrastriate cortex that appear to be specialized for processing the selected feature. The disjoint pattern of activations in extravisual brain regions during selective- and divided-attention conditions also suggests that preceptual judgements involve different neural systems, depending on attentional strategies. PMID- 1869922 TI - Relations between intracellular ions and energy metabolism: a study with monensin in synaptosomes, neurons, and C6 glioma cells. AB - Treatment of rat brain synaptosomes with 10 microM monensin stimulated activity of the Na/K pump, which enhanced oxygen consumption and lactate production. Glycolytic flux was also increased independently of the pump activation by a fall in [H+]i. Under such conditions, glycolysis provided 26% of ATP for the ouabain sensitive ATPase, a value substantially greater than the 4% obtained in veratridine-treated preparations (Erecinska and Dagani, 1990). In C6 glioma cells, a glia-derived line endowed with high rates of aerobic lactate synthesis, the cytosolic and mitochondrial ATP generation contributed 50% each for the support of the pump in the presence of 10 microM monensin. The fraction of energy utilized by the pump was greater in synaptosomes than in C6 cells. Enhancement of ion movements was accompanied by changes in the levels of high-energy phosphate compounds. Measurements with ion-sensitive microelectrodes in C6 cells and cultured neurons showed that monensin caused an increase in pHi by 0.4-0.5 unit and a parallel rise in [Na+]i. The increases in [Na+]i were about twofold in both types of cells, but the absolute values attained were much higher in neurons (40 50 mM) than in C6 cells (10-12 mM). Membrane potentials transiently declined by less than 10 mV and returned to their original values after 20 min of treatment. Rises in [Ca2+]i were small in neurons as well as in C6 cells. These changes could be explained by the known mechanism and/or consequences of monensin action. In contrast, in synaptosomes monensin caused an internal alkalinization of 0.1 0.15 pH unit, a large depolarization of the plasma membrane, and massive leakage of potassium into the external medium. The decrease in plasma membrane potential was accompanied by an increase in [Ca/+]i and release of the neurotransmitter amino acids GABA, aspartate, and glutamate. The depolarization and loss of K+ were unaffected by calcium withdrawal, replacement of chloride with gluconate, and addition of 1 mM 4-acetamido-4'-isothiocyanostilebene-2,2'-disulfonic acid (SITS), but was markedly attenuated by elimination of Na+. It is proposed that in synaptosomes monensin and/or the consequences of its action open a nonspecific cation channel that allows Na+ entry and K+ exit, with a consequent decrease in membrane potential. PMID- 1869923 TI - Isolation and functional characterization of Schwann cells derived from adult peripheral nerve. AB - To facilitate the development of autologous transplantation techniques with which to test the ability of Schwann cell (ScC) implantations to treat nervous system injury, we have developed a method for procuring large, essentially pure populations of ScCs from adult peripheral nerve. By allowing small explants of peripheral nerve trunk to undergo axonal and myelin breakdown in vitro, rather than dissociating the nerve immediately after harvest, we are able to (1) rid the explant of nearly all fibroblasts and (2) capitalize on the intrinsic ScC mitogenic response to peripheral nerve degeneration. Here, we describe a method that yields up to 98% pure ScC populations from adult rat sciatic nerve (based on cell soma and nuclear morphology, S100 staining, and behavior of dissociated cells on neurites) at cell yields of greater than 2 x 10(4) cells/mg of starting nerve weight. The purification technique was successfully applied to human tissue; human phrenic nerve yielded 98% pure ScC populations at cell yields of 2 x 10(4) cells/mg of initial nerve weight. Similar to neonatally derived ScCs, adult rat cells can be expanded in coculture with dorsal root ganglion (DRG) neurons or in isolation in the presence of glial growth factor and forskolin. Cells expanded indefinitely on DRG neurons, or up to 10 weeks on chemical mitogens, return to quiescence following removal of the mitogenic stimulus. Expanded adult-derived rat ScCs retain functional capacity, as evidenced by their ability to myelinate DRG neurites and to support regeneration of processes from embryonic rat retinal explants. PMID- 1869924 TI - A unique neuronal organization in the cat pretectum revealed by antibodies to the calcium-binding protein calbindin-D 28K. AB - The pretectum is an important center for visual reflexes. However, the location, boundaries, and connections of individual nuclei of the pretectum are incompletely understood. In cat, the traditionally defined nuclear boundaries have been placed in doubt by recent evidence showing that the retinal input to the pretectum forms four continuous projection zones that do not match the cytoarchitectural boundaries of individual pretectal nuclei defined by previous studies. We now show that antibodies to the calcium-binding protein calbindin-D 28K (CaBP) label clusters of neurons within the pretectum that match the zones of retinal termination. Four obvious cell clusters within the pretectum were labeled by CaBP antisera. Computer three-dimensional reconstruction of these cell clusters revealed that they form four distinct but continuous zones that run the rostrocaudal length of the pretectum in a medial-to-lateral direction. By combining anterograde HRP labeling of retinal terminals with CaBP immunocytochemistry, these CaBP-labeled cell clusters were found virtually to overlap the retinal projection zones. The CaBP-labeled neurons included both multipolar and fusiform morphologies, and most were medium- to large-sized cells. HRP retrograde transport studies showed that many CaBP-labeled neurons in the clusters projected to the LGN, while none projected to the inferior olive (IO). GABA-immunoreactive neurons were also found within the CaBP cell clusters, but these neurons were smaller than most CaBP-labeled neurons, and none were retrogradely labeled following HRP injections into the LGN or IO. Two-color antibody double-labeling experiments did not reveal any GABA neurons within the clusters that colocalized CaBP. In summary, calbindin is a precise marker of neuron clusters that overlap the retinal projection zones in the cat pretectum. Many of these CaBP neurons project to the LGN, and none contain GABA. PMID- 1869925 TI - Evidence for the ventral origin of oligodendrocyte precursors in the rat spinal cord. AB - The neuroepithelial cells of the mammalian neural tube are thought to give rise to all classes of differentiated neurons and macroglial cells in the adult CNS. In most cases, the regulation and timing of commitment of neuroepithelial cells to specific differentiative pathways are unknown. It has been proposed that in developing spinal cord, the macroglial cells--astrocytes and oligodendrocytes- arise either by the direct transformation of radial glial cells in the developing cord or, alternatively, by the differentiation of distinct precursor cells which migrate to presumptive white matter from the region of the central canal during development. In this study, the timing of oligodendrocyte differentiation in different levels of the spinal cord and the capacity of specific regions of the spinal cord to give rise to oligodendrocytes at various ages was tested in vitro. At embryonic day 14, all complete segments, as well as all ventral regions along the rostral-caudal axis of the spinal cord, have the capacity for oligodendrogenesis. By contrast, dorsal regions of the thoracic and lumbar spinal cord do not develop the capacity for oligodendrogenesis until later in development. The capacity of dorsal rat spinal cord to give rise to oligodendrocytes appears to be associated with the ventral-to-dorsal migration of oligodendrocyte precursors. These observations suggest that commitment to an oligodendrocyte differentiative pathway appears to occur in a distinct population of ventrally located glial precursors in the embryonic rat spinal cord. PMID- 1869927 TI - A cellular analysis of inhibition in the siphon withdrawal reflex of Aplysia. AB - Recent behavioral experiments examining the siphon withdrawal reflex of Aplysia have revealed inhibitory effects of strong tail shock, a stimulus commonly used as an unconditioned stimulus in studies of associative and nonassociative learning in Aplysia. We utilized a reduced preparation to perform a cellular analysis of tail shock-induced inhibition in the siphon withdrawal reflex. First, we carried out behavioral studies that showed that the reduced preparation exhibits a siphon withdrawal reflex to water jet stimuli, and that tail shock produces inhibitory behavioral effects comparable to those in the intact animal: (1) strong shock produces transient inhibition of nonhabituated responses, and (2) a habituated response is facilitated by weak shock, but not by strong shock, suggesting that increasing tail shock intensity recruits the inhibitory process that competes with facilitation of habituated reflexes. Next, we carried out cellular studies that showed that the amplitude of the complex EPSP in siphon motor neurons elicited by water jet stimuli to the siphon also exhibits the inhibitory patterns produced by tail shock: (1) the nondecremented complex EPSP (a neural correlate of a nonhabituated siphon withdrawal reflex) is significantly inhibited 90 sec after strong tail shock and recovers to preshock levels 10 min later, and (2) the decremented complex EPSP (a neural correlate of a habituated reflex) is significantly facilitated by weak shock, but is not facilitated by strong shock. In addition to the complex EPSP, we simultaneously examined the monosynaptic connection between siphon sensory neurons and siphon motor neurons. The monosynaptic EPSP does not show the pattern of inhibitory modulation by tail shock exhibited by the siphon withdrawal reflex and the complex EPSP: (1) the nondecremented monosynaptic EPSP is not inhibited 90 sec after strong shock, but tends to be above preshock levels; and (2) the decremented monosynaptic EPSP is facilitated by weak as well as strong tail shock. Our results suggest that an important component of the inhibitory process triggered by strong tail shock is mediated by neural elements presynaptic to the siphon motor neurons. Because modulation of the monosynaptic connection between identified siphon sensory and siphon motor neurons does not parallel the tail shock-induced inhibitory patterns observed in the siphon withdrawal reflex and in the complex EPSP, other synaptic connections are likely to play an important role in mediating tail shock-induced inhibition in the siphon withdrawal reflex. PMID- 1869926 TI - Acid-induced death in neurons and glia. AB - Lactic acidosis has been proposed to be one factor promoting cell death following cerebral ischemia. We have previously demonstrated that cultured neurons and glial are killed by relatively brief (10 min) exposure to acidic solutions of pH less than 5 (Goldman et al., 1989). In the present series of experiments, we investigated the relationship between changes in intracellular pH (pHi) and cellular viability. pHi was measured using fluorescent pH probes and was manipulated by changing extracellular pH (pHe). Homeostatic mechanisms regulating pHi in neurons and glia were quickly overwhelmed: neither neurons nor glial cells were able to maintain baseline pHi when incubated at pHe below 6.8. Neuronal and glial death was a function of both the degree and the duration of intracellular acidification, such that the LD50 following timed exposure to HCl increased from pH, 3.5 for 10-min acid incubations to pHi 5.9 for 2-hr exposures and pHi 6.5 for 6-hr exposures. Replacement of HCl with lactic acid raised the LD50 to pHi 4.5 for 10-min acid exposures, but did not change the LD50 for longer exposures: pHi measurements concurrent with extracellular acidification suggested that the greater cytotoxicity of lactic acid relative to that of HCl was caused by the more rapid intracellular acidification associated with lactic acid. The onset of death after exposure to moderately acidic solutions was delayed in some cells, such that death of the entire cell population became evident only 48 hr after acid exposure. During this latency period, cellular viability indices and ATP levels fell in parallel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869928 TI - Serotonin mimics tail shock in producing transient inhibition in the siphon withdrawal reflex of Aplysia. AB - Tail shock-induced modulation of the siphon withdrawal reflex of Aplysia has recently been shown to have a transient inhibitory component, as well as a facilitatory component. This transient behavioral inhibition is also seen in a reduced preparation in which a cellular reflection of the inhibitory process, tail shock-induced inhibition of complex EPSPs in siphon motor neurons, is observed. The biogenic amine serotonin (5-HT) is known to play a role in the facilitatory aspects of sensitization in Aplysia. The aim of this article was to examine whether 5-HT might also contribute to the inhibitory effects of tail shock in the siphon withdrawal reflex. To examine this question, we carried out two kinds of experiments. First, in the isolated abdominal ganglion, we recorded intracellularly from siphon motor neurons and examined the effects of 5-HT on (1) complex (polysynaptic) EPSPs, produced by siphon nerve stimulation, and, simultaneously, (2) monosynaptic EPSPs from siphon sensory neurons. We found that, paralleling the effects of tail shock in the reduced preparation, 5-HT produced transient inhibition of the complex EPSP; the monosynaptic EPSP was facilitated by 5-HT. Second, we examined the behavioral effects of 5-HT on siphon withdrawal in a reduced preparation. We found that 5-HT again paralleled tail shock by producing transient inhibition of the siphon withdrawal reflex. Our results suggest that, in addition to its well-established facilitatory role in reflex modulation in Aplysia, 5-HT might play an important inhibitory role, as well. PMID- 1869929 TI - Existence of different subtypes of nicotinic acetylcholine receptors in the rat habenulo-interpeduncular system. AB - Neuronal nicotinic ACh receptors (nAChRs) are present in the rat medial habenula (MHB) and interpeduncular nucleus (IPN), two brain regions connected through the fasciculus retroflexus (FR). The goal of the present study was to compare the electrophysiological and pharmacological characteristics of nAChRs located at pre and postsynaptic sites within the MHB-IPN system. nAChRs located on the soma of IPN neurons were studied using patch-clamp techniques and a preparation of acutely isolated neurons. Whole-cell currents evoked by Ach and nicotine showed an intense rectification at positive membrane potentials. nAChR channels were relatively nonselective for cations, had a unitary conductance of 35 pS, and were activated by several nicotinic agonists with the following rank order: cytisine greater than ACh greater than nicotine greater than dimethylphenylpiperazinium (DMPP). They were blocked by mecamylamine, hexamethonium, curare, and dihydro beta-erythroidine (DHBE), but were insensitive to alpha-bungarotoxin and neuronal bungarotoxin. In contrast, nAChRs recorded on the soma of MHB neurons under equivalent experimental conditions exhibited different characteristics for single channel conductance and agonist and antagonist sensitivity. The pharmacological properties of presynaptic nAChRs in the IPN were analyzed in a rat brain slice preparation. Stimulation of the FR produced a presynaptic afferent volley recorded in the rostral subnucleus of the IPN. Nicotinic agonists decreased the amplitude of the afferent volley with different efficacies: nicotine greater than cytisine greater than ACh greater than DMPP. The action of nicotine was insensitive to alpha-bungarotoxin and to neuronal bungarotoxin, but was blocked by mecamylamine, hexamethonium, curare, and DHBE, with IC50 values different from those reported for IPN postsynaptic nAChRs. This study thus demonstrates the functional diversity of nAChRs in the rat CNS. PMID- 1869930 TI - Genetic hypothyroid mice: normal cerebellar morphology but altered glycerol-3 phosphate dehydrogenase in Bergmann glia. AB - The present study was undertaken to investigate the effects of thyroid deficiency on cerebellar development with mouse endocrine genetic models. Four types of mutant mice, the growth hormone- and thyroid hormone-deficient Snell dwarf mouse (dw/dw), the growth hormone-deficient little mouse (lit/lit), the primary hypothyroid mouse (hyt/hyt), and the congenital genital goiter mouse (cog/cog) were analyzed for expression of the glial enzyme marker glycerol-3-phosphate dehydrogenase (GPDH) and several other marker proteins. GPDH expression, as determined by enzyme activity and Northern blot analysis, was reduced by about 50% in the cerebellum and brainstem of the three hypothyroid mutant mice. No reduced expression was found in any region of the brain of the growth hormone deficient lit/lit mutant. Visualization of GPDH by immunohistology showed that the immunoreactive enzyme was strikingly reduced in the Bergmann glial cells of dw/dw, hyt/hyt, and cog/cog mutant mice, particularly in the radial glial processes. To evaluate the specificity of the effect on GPDH expression, we also examined the expression of the glial cell-specific S-100 protein by immunohistology. In all mutant cerebella, both the intensity and pattern of staining of the Bergmann glial cells were indistinguishable from that of normal controls, suggesting that the Bergmann glial cells are morphologically normal in the hypothyroid mice. The morphology of the Purkinje cell neurons was similarly visualized by immunohistology using an antiserum specific for the microtubule associated proteins. Surprisingly, the morphology of the Purkinje cell dendritic arborization also appeared unaltered in the hypothyroid mice. The results suggest that the morphological development of the mouse cerebellum is relatively unaffected by hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1869931 TI - Frank H. Mayfield, M.D., 1908-1991. PMID- 1869932 TI - Lateral parascapular extrapleural approach to the upper thoracic spine. AB - The upper thoracic vertebrae are difficult to approach surgically because of the narrowing of the thoracic inlet, the proximity of the brachial plexus, and the parascapular shoulder musculature. A novel lateral parascapular extrapleural approach to the upper thoracic vertebrae is described. The parascapular shoulder musculature (trapezius, levator scapulae, and rhomboid muscles) is reflected off the spinous processes to the scapula as a musculocutaneous flap, preserving the neurovascular supply. The paraspinal musculature is mobilized and retracted, and the upper dorsal ribs are removed with caution to avoid injury to the C-8 and T-1 nerve roots. The rami communicantes are transected, and the sympathetic chain is displaced anterolaterally. The T2-4 vertebrae can be approached unobstructed. The T-1 nerve root obstructs posterolateral access to the T-1 vertebra, necessitating an inferolateral approach underneath the T-1 nerve root axilla. Four patients with compressive myelopathy from upper thoracic vertebral metastases underwent neural decompression, vertebral reconstruction, and posterior spinal fixation with this approach. Their postoperative neurological status was either unchanged or improved. Complications included radiographic pleural effusion and superficial wound dehiscence; one patient required posterior spinal reinstrumentation for progressive kyphosis. One patient developed pneumonia 7 days postoperatively which was unresponsive to appropriate treatment. It is believed that the anatomical limitations to this region have been overcome, and that excellent exposure of the T1-4 vertebrae for neural decompression and vertebral reconstruction can be performed safely. A major advantage is that posterior spinal fixation can be carried out simultaneously. PMID- 1869933 TI - Intracranial aneurysms in sickle-cell anemia: clinical features and pathogenesis. AB - Intracranial aneurysms are an unusual complication of sickle-cell anemia; only 15 patients have been described in the world literature. An additional 15 patients with sickle-cell anemia and subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms are presented. There was a high incidence of multiple aneurysms (60%); some of which were in unusual locations. The clinical and pathological features of this series of patients have provided a paradigm for acquired aneurysm formation that may be applicable to other intracranial aneurysms. Thirteen patients underwent craniotomy and clip ligation; the perioperative management of these patients is discussed. Of these 13, eight had a good recovery, three were left with moderate disability, one patient died of surgical complications, and one died of complications related to sickle-cell anemia. Two of the 15 patients died of SAH. The authors propose that endothelial injury from the abnormal adherence of sickle erythrocytes to the endothelium is the initiating event in arterial wall injury. Subsequently, there is fragmentation of the internal elastic lamina and degeneration of the smooth muscle layer. Hemodynamic stress at these loci of arterial wall damage results in aneurysm formation. This hypothesis also explains other cerebrovascular manifestations of sickle-cell anemia, namely vaso-occlusive disease and hemorrhage without aneurysm formation. Pathological material from this series and data from the literature are presented to support this hypothesis. PMID- 1869934 TI - Surgical treatment of limbic epilepsy associated with extrahippocampal lesions: the problem of dual pathology. AB - The authors present their review of 178 patients who underwent en bloc temporal lobectomies as surgical treatment for intractable epilepsy. Hippocampal cell density was quantitatively analyzed and the histology of the anterior temporal lobe was reviewed. Fifty-four patients (30.3%) had evidence of extrahippocampal lesions in addition to neuronal cell loss within the hippocampus (the dual pathology group). The pattern of cell loss was analyzed in the remaining 124 cases (69.7%) with no extrahippocampal pathology, and compared with that of the dual pathology group and a control group of four nonepileptic patients. Hippocampal cell loss was found in almost all epileptic patients compared to the control group. Severe cell loss greater than 30% of control values was found in 88.7% of patients without extrahippocampal lesions, but in only 51.8% of patients with dual pathology. The difference between these two groups was statistically significant (p less than 0.001). In the dual pathology group, lesions of different pathology had a significant relationship with the degree of hippocampal cell loss: all 12 patients with glioma had mild cell loss, whereas all 13 patients with heterotopia were associated with severe cell loss. Severity of hippocampal cell loss was also analyzed in relation to seizure history: a prior severe head injury was associated with severe cell loss. Other factors such as seizure duration, secondary generalization, or family history of seizures were not associated with hippocampal damage. Dual pathology may produce a combination of neocortical and temporolimbic epilepsies that warrants a precise definition of the true epileptogenic area prior to surgical treatment. PMID- 1869935 TI - Unruptured intracranial aneurysms: seizures and antiepileptic drug treatment following surgery. AB - Twenty-one patients operated on for unruptured intracranial aneurysms were studied retrospectively in order to identify the incidence of postoperative seizures, factors predictive of seizures, and the response to discontinuation of antiepileptic drugs. The overall risk of postoperative seizures in initially seizure-free patients was 15.7%. Although seizures were not uncommon, antiepileptic drugs were successfully tapered in most of the patients before 12 months. PMID- 1869936 TI - Retrospective long-term follow-up analysis in 21 patients with chordomas of various sites treated at a single institution. AB - Twenty-one patients with chordoma were treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, between 1949 and 1986. Thirteen patients had sacrococcygeal tumors, five had clival tumors, two had nasopharyngeal tumors, and one had a lumbar spine tumor. Nine patients were treated with surgery alone, eight patients with subtotal resection and postoperative irradiation, and four patients with radiotherapy alone after biopsy. The 5- and 10-year actuarial survival rates were 74% and 46%, respectively. The 10-year actuarial survival rate was significantly better in patients treated with surgery alone or surgery and irradiation than in those treated with radiotherapy alone (52%, 32%, and 0%, respectively, p = 0.02). Although all patients ultimately suffered a recurrence, those with lumbosacral tumors treated with surgery and irradiation had a longer mean disease-free survival period (6.6 years) than those treated with surgery alone (4.1 years) (p = 0.08). Disease-free survival times of patients with base of the skull tumors was not significantly different between the treatment groups. Irradiation after resection of chordomas appears to increase the time to first relapse in lumbosacral tumors and should be considered after subtotal resection. PMID- 1869937 TI - The relationship between intelligence and memory following minor or mild closed head injury: greater impairment in memory than intelligence. AB - This study investigated the performance of patients with minor or mild closed head injury and age/education-matched normal controls on the Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the Wechsler Memory Scale-Revised (WMS R). The results demonstrated that the control group had significantly higher scores than the patients with closed head injury on all WAIS-R and WMS-R index scores. Further analysis revealed that the patients with closed head injury showed a greater impairment in delayed memory when directly compared to intellectual performance that was not seen in the control group. These results are discussed in relation to findings in patients with more severe closed head injury, the construction of the WAIS-R and the WMS-R, and the performance patterns of the two groups. PMID- 1869938 TI - Texas Scottish Rite Hospital rod instrumentation for thoracic and lumbar spine trauma. AB - The authors present their experience with 28 patients who had incurred unstable thoracic or lumbar spine fractures and who were intraoperatively stabilized with the Texas Scottish Rite Hospital (TSRH) universal instrumentation system. These patients were treated over a 1-year period and reflect an evolving insight into the treatment of thoracic and lumbar spine trauma with universal instrumentation. The TSRH instrumentation system appears equivalent to the more established Cotrel Dubousset system in most respects. The construct design of the TSRH system facilitates the safe application of a rigid spinal implant. No cases of instability or pseudoarthrosis were observed during an average follow-up period of 9 months, (minimum 3 months). As the surgical treatment plan evolved, shorter and more compact constructs were increasingly utilized. There were no cases of instrumentation failure, regardless of the number of spinal levels fused or the number of levels instrumented. The value of using short rods when possible is emphasized: they may decrease the incidence of delayed instability and discomfort related to loosening at the hook/bone interface compared to that observed when long-rod systems are used in association with short spine fusions causing a fusion/instrumentation mismatch. PMID- 1869939 TI - Microvascular decompression for hemifacial spasm. Patterns of vascular compression in unsuccessfully operated patients. AB - To determine the causative factors of unsuccessful microvascular decompression for hemifacial spasm, the follow-up results in 53 patients were assessed retrospectively. The mean follow-up period was 36 months. There were 32 patients who had compression of the seventh cranial nerve ventrocaudally by an anterior inferior cerebellar artery (AICA) or a posterior inferior cerebellar artery. Of these 32 patients, 30 (94%) had excellent postoperative results. Of 14 patients with more severe compression by the vertebral artery, nine (64%) had excellent results, three (21%) had good results, and two (14%) had poor results; in this group, three patients with excellent results experienced transient spasm recurrence. There were seven patients in whom the meatal branch of the AICA coursed between the seventh and eighth cranial nerves and compressed the dorsal aspect of the seventh nerve; this was usually associated with another artery compressing the ventral aspect of the nerve ("sandwich-type" compression). Of these seven patients, five (71%) had poor results including operative failure in one and recurrence of spasm in four. The authors conclude that the clinical outcome was closely related to the patterns of vascular compression. PMID- 1869940 TI - Optochiasmal arachnoiditis following muslin wrapping of ruptured anterior communicating artery aneurysms. AB - Optochiasmal arachnoiditis has been reported following treatment of ruptured intracranial aneurysms, particularly arising from the anterior communicating artery. It has been suggested that the accompanying loss of vision is due to a muslin-induced optic neuropathy. This paper considers five cases of this condition; the response to steroid therapy was beneficial in three cases. A review of the literature is included. The arachnoiditis is considered to be due to an inflammatory response to muslin gauze placed close to the optic nerves and chiasm. PMID- 1869941 TI - Efficacy of dorsal longitudinal myelotomy in treating spinal spasticity: a review of 20 cases. AB - The authors report their experience using dorsal longitudinal myelotomy in treating spasticity in 20 patients with complete spinal cord injuries. These patients suffered from severe painful flexor/extensor spasms that prevented them from wheelchair ambulation and/or their decubitus ulcers healing. All were receiving large doses of various oral drugs, including baclofen, which had failed to control their spasticity, and all underwent a modification of a posterior T myelotomy as first described by Bischof. All 20 patients enjoyed immediate complete relief of their painful spasms, although two (10%) eventually experienced return of their spasms and are thus classified as long-term failures. Seventeen patients succeeded in markedly reducing, or being completely weaned from, their antispasmodic medications. In 11 of 14 patients, nonhealing decubitus ulcers subsequently healed with treatment. Bladder function was unchanged from the preoperative status in all patients. Chronic intrathecal baclofen infusion has recently been reported as an effective treatment of the spasticity of paraplegia. The results of this study, along with previous reports advocating dorsal longitudinal myelotomy, suggest that this approach is an efficacious alternative to chronic baclofen infusion in reducing spasticity for complete paraplegics. Considering the cost of the infusion pump, along with the fact that chronic intrathecal baclofen therapy necessitates long-term medical supervision, it appears that myelotomy is superior for this select group of patients who have no hope of regaining voluntary motor function. PMID- 1869942 TI - Treatment of chronic pain by epidural spinal cord stimulation: a 10-year experience. AB - Epidural spinal cord stimulation by means of chronically implanted electrodes was carried out on 121 patients with pain of varied benign organic etiology. In 116 patients, the pain was confined to the back and lower extremities and, of these, 56 exhibited the failed-back syndrome. Most patients were referred by a pain management service because of failure of conventional pain treatment modalities. Electrodes were implanted at varying sites, dictated by the location of pain. A total of 140 epidural implants were used: 76 unipolar, 46 Resume electrodes, 12 bipolar, and six quadripolar. Patients were followed for periods ranging from 6 months to 10 years, with a mean follow-up period of 40 months. Forty-eight patients (40%) were able to control their pain by neurostimulation alone. A further 14 patients (12%), in addition to following a regular stimulation program, needed occasional analgesic supplements to achieve 50% or more relief of the prestimulation pain. Pain secondary to arachnoiditis or perineural fibrosis following multiple intervertebral disc operations, when predominantly confined to one lower extremity, seemed to respond favorably to this treatment. Uniformly good results were also obtained in lower-extremity pain secondary to multiple sclerosis. Pain due to advanced peripheral vascular disease of the lower limbs was well controlled, and amputation below the knee was delayed for up to 2 years in some patients. Pain due to cauda equina injury, paraplegic pain, phantom-limb pain, pure midline back pain without radiculopathy, or pain due to primary bone or joint disease seemed to respond less well. Patients who responded to preliminary transcutaneous electrical nerve stimulation generally did well with electrode implants. Notable complications included wound infection, electrode displacement or fracturing, and fibrosis at the stimulating tip of the electrode. Three patients in this series died due to unrelated causes. Epidural spinal cord stimulation has proven to be an effective and safe means of controlling pain on a long-term basis in selected groups of patients. The mechanism of action of stimulation-produced analgesia remains unclear; further studies to elucidate it might allow spinal cord stimulation to be exploited more effectively in disorders that are currently refractory to this treatment modality. PMID- 1869943 TI - Etiology of cerebral vasospasm in primates. AB - A primate model was used to determine whether oxyhemoglobin (OxyHb), methemoglobin (MetHb), or bilirubin is likely to be responsible for cerebral vasospasm following subarachnoid hemorrhage (SAH). Forty cynomolgus monkeys were randomly assigned to one of five groups. On Day 0, each animal underwent angiography followed by right craniectomy and placement of an Ommaya reservoir with its catheter adjacent to the right middle cerebral artery (MCA). The animals received intrathecal injections twice a day for 6 days of one of the following solutions: mock cerebrospinal fluid (CSF); OxyHb; MetHb; bilirubin; or supernatant fluid from an incubated mixture of autologous blood and mock CSF. On Day 7, angiography was repeated and the animals were killed. Comparison of angiograms obtained on Day 0 and Day 7 of the experiment showed significant vasospasm of the right MCA and the right anterior cerebral and internal carotid arteries in the animal groups that had received OxyHb or supernatant fluid. There was a smaller reduction in diameter of the same vessels in the bilirubin group (not statistically significant), while no effects were observed in the groups receiving MetHb or mock CSF. Electron microscopy of the right MCA's gave results consistent with the angiographic findings. One monkey in the OxyHb group developed a delayed-onset right MCA infarction. These data suggest that OxyHb is the cause of cerebral vasospasm following SAH. PMID- 1869944 TI - Surgical manipulation of primate cerebral arteries in established vasospasm. AB - It is generally believed that surgery in the face of angiographic vasospasm is dangerous due to an increased incidence of postoperative cerebral ischemia. One theory is that arterial narrowing is exacerbated by surgical manipulation of vasospastic vessels during aneurysm dissection and clipping. This theory was tested in a primate model of cerebral vasospasm and the results reported. Six monkeys underwent baseline cerebral angiography, followed by induction of subarachnoid hemorrhage (SAH) on both sides of the circle of Willis. An equal amount of fresh autologous blood clot was placed around each internal carotid, anterior cerebral, and middle cerebral artery. Six days later, angiography was repeated and the right craniectomy was reopened for clot evacuation and surgical manipulation of the right cerebral arteries, including placement of a temporary aneurysm clip on the right middle cerebral artery. The left cerebral arteries were not exposed or manipulated, and served as controls. Twenty-four hours later angiography was repeated, then the animals were killed. Equal and significant vasospasm (greater than 40% reduction in vessel caliber compared to baseline, p less than 0.05) was seen in the middle cerebral arteries on both sides of the circle of Willis in all animals 6 and 7 days after SAH. There was no significant change in the severity of vasospasm on Day 7 compared with Day 6 in the right cerebral arteries. Increased risk of postoperative cerebral ischemia for surgery in the peak vasospasm period may be due to mechanisms other than increased arterial narrowing precipitated by surgical manipulation. PMID- 1869945 TI - Effects of hypothermia and hyperthermia on the reactivity of rat intracerebral arterioles in vitro. AB - The effects of hypothermia and hyperthermia on the cerebral microcirculation were studied using isolated perfused intracerebral (parenchymal) arterioles obtained from rats. In a temperature-dependent manner, hypothermia (20.0 degrees to 35.0 degrees C) dilated the spontaneous tone developed by the arterioles and also diminished their contractile response to potassium and prostaglandin F2 alpha. In contrast, hyperthermia (40.0 degrees to 45.0 degrees C) induced a biphasic response consisting of initial vasoconstriction and secondary vasodilation. Exposure of the vessels to 45.0 degrees C for 30 minutes irreversibly abolished the spontaneous tone and responsiveness of the arterioles when the temperature of the preparation was returned to 37.5 degrees C. In calcium-free solutions, however, the arteriolar diameter was not affected within a temperature range of 20.0 degrees to 45 degrees C. Furthermore, arterioles that had been in a calcium free solution during exposure to 45 degrees C temperature recovered their viability at 37.5 degrees C. These results suggest that changes in ambient temperature alter calcium-induced contraction in arteriolar smooth muscle, and that the irreversible effects of hyperthermia on the arterioles are dependent upon extracellular calcium. These studies indicate that alterations in brain temperature may affect the pathogenesis of cerebral ischemia by mechanisms that are in part independent of parenchymal metabolism. PMID- 1869946 TI - Electrophysiological studies of various graft lengths and lesion lengths in repair of nerve gaps in primates. AB - Electrophysiological studies were used to evaluate neurological recovery in 14 rhesus monkeys with different nerve lesion lengths and graft lengths. After exposure of both sciatic nerves in each animal, baseline evoked nerve action potentials, muscle action potentials, and muscle strength values were determined for the posterior tibial nerves. Each nerve was then crushed over a measured distance. Three weeks later, the crushed segments were resected and the defects repaired with sural nerve grafts. In seven animals, 20-mm resection sites were repaired by 4 x 20-mm grafts in one leg and by 4 x 40-mm grafts contralaterally. In the other seven animals, the lengths of resection sites were 10 mm in one leg and 30 mm contralaterally; both nerve defects in these animals were repaired by 4 x 30-mm grafts. Electrophysiological studies were repeated at one interval of either 4, 7, or 12 months after repair. Postoperative electrophysiological values were compared to baseline values and described by the mean values and by percent recovery. Muscle strength recovery was significantly better in limbs with short lesions. In animals with identical lesion lengths, lesions repaired with shorter grafts (the same length as the defect) did significantly worse than did lesions repaired with longer grafts. This may suggest that any degree of tension at the graft repair site has a deleterious effect on functional nerve regeneration. Nevertheless, it was generally found that nerve lesion length had the greatest negative effect on functional nerve regeneration. PMID- 1869947 TI - Induction of cytosolic free calcium elevation in rat vascular smooth-muscle cells by cerebrospinal fluid from patients after subarachnoid hemorrhage. AB - The purpose of this study was to determine the effects of cerebrospinal fluid (CSF) from patients with subarachnoid hemorrhage (SAH) on cytosolic free calcium in cultured rat vascular smooth-muscle cells using the fluorescent intracellular calcium indicator fura-2/AM. Samples of CSF were collected from 12 patients (seven with and five without vasospasm) on Days 2, 6, 11, and 16 after SAH. Control CSF samples were obtained from five patients 6 to 9 months after they had undergone successful aneurysm surgery following an SAH. All CSF samples in both the non-vasospasm and vasospasm groups, regardless of the day of sampling after the SAH, induced significantly higher transient intracellular calcium elevations when compared to levels induced by control CSF. Furthermore, the addition of 2 mM ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetra-acetic acid (EGTA) caused a slight reduction in the peak height in the CSF-induced intracellular calcium rise which declined more rapidly to basal levels than those studied without EGTA. In the non-vasospasm group, the intracellular calcium concentration remained stable after SAH throughout the study period. In contrast, in the vasospasm group, this concentration was highest on Day 2 post-SAH, but sharply decreased on Day 6 and rose again on Day 11. This result correlated with the clinical signs of vasospasm in these patients. These findings indicated that the intracellular calcium elevations induced by CSF obtained after SAH were due to the combination of the influx of extracellular calcium and the mobilization of intracellular calcium from storage sites. The changes in intracellular calcium concentrations in vascular smooth-muscle cells induced by CSF obtained from patients on successive days following SAH suggest that the substances that induce this repeat calcium elevation on Day 11 post-SAH may be the key spasmogens for vasospasm after SAH. PMID- 1869948 TI - Cerebral amyloid angiopathy presenting as multiple intracranial lesions on magnetic resonance imaging. Case report. AB - Cerebral amyloid angiopathy is recognized as an important cause of spontaneous intracerebral hemorrhage in the elderly normotensive patient. Magnetic resonance (MR) imaging characteristics of this disease entity are rarely mentioned in the literature. The MR imaging findings of an elderly normotensive patient presenting with an acute spontaneous intracerebral hemorrhage secondary to amyloid angiopathy are reported and a brief review of amyloidosis is presented. PMID- 1869949 TI - Excision of cavernous angioma with preservation of coexisting venous angioma. Case report. AB - The case of a patient presenting with dysphasic seizures due to a cavernous angioma coexisting with a venous malformation is reported. The cavernous angioma was resected with preservation of the venous malformation, as confirmed by postoperative studies. The patient was seizure-free following surgery. PMID- 1869950 TI - Anomalous rib presenting as cervical myelopathy: a previously unreported variant of Klippel-Feil syndrome. Case report. AB - A patient is reported with an anomalous rib that caused compression of the cervical spinal cord and presented with cervical myelopathy. This appears to be the first reported instance of this particular anomaly. The clinicoanatomical aspects of this case are discussed. PMID- 1869951 TI - Cerebral sparganosis caused by Spirometra mansonoides. Case report. AB - Cerebral sparganosis is an uncommon parasitic zoonosis caused by the migrating larva of the genus Spirometra mansonoides. The clinical and computerized tomography presentation, as well as the operative and histopathological findings, of the first known case in Mexico are detailed. The dead larva elicited intense acute inflammation resulting in focal encephalitis. Surgical removal of the larva yielded excellent results. PMID- 1869952 TI - Traumatic pericallosal aneurysm in a patient with no major trauma. Case report. AB - The case of a young woman who developed a traumatic distal anterior cerebral artery ("pericallosal") aneurysm from a roller-coaster ride is described. She presented with a subarachnoid hemorrhage (SAH) restricted to the interhemispheric fissure. The initial angiogram was normal but repeat angiography at 8 days revealed the aneurysm. After craniotomy and clipping the patient made a satisfactory recovery. This is the only reported case of a traumatic aneurysm arising under circumstances not usually considered as trauma. It raises questions about the pathophysiology of the formation of such aneurysms and suggests that traumatic pericallosal aneurysms should be considered in SAH of unknown etiology. This case provides further evidence that repeat angiography occasionally helps reveal an aneurysm when the initial study fails to do so. PMID- 1869953 TI - Stabilization of traumatic atlanto-occipital dislocation. Case report. AB - Traumatic atlanto-occipital dislocation is most often fatal. Consequently, there are only scattered case reports of patients surviving this injury, and treatment modalities are anecdotal and varied. The case of an 18-year-old woman who suffered an anterior atlanto-occipital dislocation as the result of a motor vehicle accident is presented. Rigid posterior fixation and complete reduction of the dislocation were achieved using an anatomically contoured steel loop secured to the occiput and cervical vertebrae. The addition of cancellous bone to the graft afforded long-term stability. This operative treatment provided anatomical realignment of the dislocation and allowed early mobilization of the patient with the use of aggressive rehabilitation. Previously reported cases of patients surviving anterior atlanto-occipital dislocation are reviewed. The use of cervical traction, halo bracing, and operative stabilization is discussed. PMID- 1869954 TI - Transoral transclival clipping of anterior inferior cerebellar artery aneurysm using new rotating applier. Technical note. AB - A large, partly calcified aneurysm buried in the pons and arising from the junction of the basilar artery and the anterior inferior cerebellar artery was successfully occluded using a variangle aneurysm clip with a new rotating pistol grip applier which allowed transoral access. The authors believe that the new applier, used in association with the current techniques for dural closure, allows for safe transoral surgery for basilar aneurysms. PMID- 1869955 TI - Stereotactic suboccipital transcerebellar biopsy under local anesthesia using the Cosman-Roberts-Wells frame. Technical note. AB - Previously reported suboccipital transcerebellar stereotactic biopsy methods, performed with the patient in the prone position, have required general endotracheal anesthesia. A technique is described for performing such biopsies with the patient in the lateral decubitus position, under local anesthesia. Phantom planning and routine computerized tomography graphics allow the selection of a safe entry point and intra-axial trajectory to the lesion. The time required for data acquisition and the operative procedure itself compares well with that of more routine biopsy techniques. PMID- 1869956 TI - The Sterling Hall of Medicine, Yale University School of Medicine. AB - A brief history of the Sterling Hall of Medicine at Yale University is presented; this building was erected and dedicated in 1925. This event signified the beginning of a new era for the Yale University School of Medicine, making it possible to attract a caliber of faculty that has enabled the School to attain its present place in medical education. PMID- 1869957 TI - Treatment for intraventricular hemorrhage. PMID- 1869958 TI - Interlaminar clamp for posterior fusions. PMID- 1869960 TI - Surgery for acoustic neurinomas. PMID- 1869959 TI - Valsalva maneuver: a misnomer? PMID- 1869961 TI - Accessory limbs and spinal dysraphism. PMID- 1869962 TI - Angiography following aneurysm surgery. PMID- 1869963 TI - Molecular medicine: from science to service. PMID- 1869964 TI - Single-photon emission computed tomography in human immunodeficiency virus encephalopathy: a preliminary report. AB - Depression or psychosis in a previously asymptomatic individual infected with the human immunodeficiency virus (HIV) may be psychogenic, related to brain involvement by the HIV or both. Although prognosis and treatment differ depending on etiology, computed tomography (CT) and magnetic resonance imaging (MRI) are usually unrevealing in early HIV encephalopathy and therefore cannot differentiate it from psychogenic conditions. Thirty of 32 patients (94%) with HIV encephalopathy had single-photon emission computed tomography (SPECT) findings that differed from the findings in 15 patients with non-HIV psychoses and 6 controls. SPECT showed multifocal cortical and subcortical areas of hypoperfusion. In 4 cases, cognitive improvement after 6-8 weeks of zidovudine (AZT) therapy was reflected in amelioration of SPECT findings. CT remained unchanged. SPECT may be a useful technique for the evaluation of HIV encephalopathy. PMID- 1869965 TI - HIV encephalopathy: on the road to a useful diagnostic test? PMID- 1869966 TI - Computer-assisted superimposition of magnetic resonance and high-resolution technetium-99m-HMPAO and thallium-201 SPECT images of the brain. AB - A method for registering three-dimensional CT, MR, and PET data sets that require no special patient immobilization or other precise positioning measures was adapted to high-resolution SPECT and MRI and was applied in 14 subjects (five normal volunteers, four patients with dementia (Alzheimer's disease), two patients with recurrent glioblastoma, and three patients with focal lesions (stroke, arachnoid cyst and head trauma]. T2-weighted axial magnetic resonance images and transaxial 99mTc-HMPAO and 201Tl images acquired with an annular gamma camera were merged using an objective registration (translation, rotation and rescaling) program. In the normal subjects and patients with dementia and focal lesions, focal areas of high uptake corresponded to gray matter structures. Focal lesions observed on MRI corresponded to perfusion defects on SPECT. In the patients who had undergone surgical resection of glioblastoma followed by interstitial brachytherapy, increased 201Tl corresponding to recurrent tumor could be localized from the superimposed images. The method was evaluated by measuring the residuals in all subjects and translational errors due to superimposition of deep structures in the 12 subjects with normal thalamic anatomy and 99mTc-HMPAO uptake. This method for superimposing magnetic resonance and high-resolution SPECT images of the brain is a useful technique for correlating regional function with brain anatomy. PMID- 1869967 TI - Assessment of systolic thickening with thallium-201 ECG-gated single-photon emission computed tomography: a parameter for local left ventricular function. AB - We measured left ventricular (LV) systolic thickening expressed as a systolic thickening ratio in 28 patients, using 201Tl ECG-gated SPECT. Five normals, 15 patients with prior myocardial infarction, 5 with hypertrophic cardiomyopathy, and 3 with dilated cardiomyopathy were studied. The systolic thickening ratio was calculated as [(end-systolic--end-diastolic pixel counts) divided by end diastolic pixel counts], using the circumferential profile technique of both end diastolic and end-systolic short axial images. Functional images of the systolic thickening ratio were also displayed with the "bull's-eye" method. The mean systolic thickening ratio thus calculated were as follows: normals, 0.53 +/- 0.05 (mean +/- 1 s.d.); non-transmural prior myocardial infarction, 0.33 +/- 0.09; transmural prior myocardial infarction, 0.14 +/- 0.05; hypertrophic cardiomyopathy in relatively nonhypertrophied areas, 0.56 +/- 0.11; hypertrophic cardiomyopathy in hypertrophied areas, 0.23 +/- 0.07; and dilated cardiomyopathy, 0.19 +/- 0.02. The systolic thickening ratio analysis by gated thallium SPECT offers a unique approach for assessing LV function. PMID- 1869968 TI - An analysis of the arterial input curve for technetium-99m-HMPAO: quantification of rCBF using single-photon emission computed tomography. AB - Arterial radioactivity content after the intravenous administration of HMPAO in seven human subjects was analyzed. Arterial sampling of 99mTc-HMPAO was performed on each subject over a 25-min period postinjection. The lipophilic fraction of the tracer present in the blood was rapidly extracted with octanol. An analysis of the time course of the extracted and nonextracted octanol fractions was performed in order to calculate the arterial input of the tracer available for brain extraction. HMPAO net regional brain clearances were then calculated and compared with rCBF values obtained in the same patients using 99mTc-microspheres injected into the left ventricle of the heart. HMPAO brain clearances were 0.41 +/- 0.01 and 0.27 +/- 0.01 ml/min/g for grey and white matter, respectively. Linear regression analysis was performed and the following result was obtained: clearance (HMPAO) = 0.07 + 0.43 . rCBF with a high significance (p less than 0.001). This equation can be used for the transformation of HMPAO clearances into rCBF values. Our study demonstrates that by using HMPAO and SPECT it is possible to obtain a quantitative estimate of rCBF in humans. PMID- 1869970 TI - Noninvasive grading of musculoskeletal tumors using PET. AB - Twenty-five patients with mass lesions involving the musculoskeletal system were studied with positron emission tomography (PET) in order to determine if a relationship exists between histologic grade and tumor uptake of [fluorine-18]2 deoxy-2-fluoro-D-glucose (FDG). There were 6 benign lesions and 19 malignant lesions of various grades. A high correlation (Rho = 0.83) was found between the normalized uptake of tracer and the NCl grade. The high-grade malignancies had significantly greater (p = 0.0091) uptake of FDG than the combination of benign lesions and low-grade malignancies. All lesions with a normalized uptake value of 1.6 or greater were high-grade, while all lesions less than 1.6 represented either benign tumors or low grade malignancies. This strong relationship between FDG uptake and grade among neoplasms from a wide variety of cell types within a single organ system suggests that the technique may be useful in predicting grade even when the cell type is unknown. PMID- 1869969 TI - Toward absolute quantitation of cerebral blood flow using technetium-99m-HMPAO and a single scan. PMID- 1869971 TI - Multigated blood-pool imaging using heart sounds. AB - A method to trigger multigated blood-pool (MGBP) acquisition using both the first and second heart sound has been developed. The heart sound gating (HSG) circuitry identifies, individually, both the first (S1) and second (S2) heart sounds from their timing relationship alone, and provides two trigger points during the cardiac cycle. First heart sound gating may be performed to assess the systolic ejection portion of the cardiac cycle, with S2 gating utilized for reproduction of the diastolic filling portion of the cycle. Heart sound gating has been applied to twenty patients who underwent analysis of left ventricular function, and compared to conventional ECG-gated MGBP. Left ventricular ejection fractions calculated from MGBP studies using a first and a second heart sound trigger correlated well with conventional ECG gated acquisitions in patients adequately gated by HSG and ECG. Heart sound gating may be utilized in patients with rapidly changing heart rates, as S1 and S2 precisely define end-diastole and end-systole, respectively, and in situations when the ECG is inadequate for gating purposes. PMID- 1869972 TI - The effect of metabolic milieu on cardiac PET imaging using fluorine-18 deoxyglucose and nitrogen-13-ammonia in normal volunteers. AB - Cardiac PET imaging using 13N-ammonia and 18FDG was performed on 17 normal volunteers in the glucose-loaded and fasted states. PET images (glucose-loaded and fasted) were subjected to qualitative visual analysis using the descriptors: image quality, FDG blood-pool activity, ammonia lung field activity, and clinical interpretability. Glucose-loaded studies had better image quality, diminished FDG blood-pool activity, and were more often clinically interpretable compared to fasted studies. Dietary state did not affect 13N-ammonia study parameters. Using a semi-quantitative region of interest method, 18FDG myocardial activity was homogeneous and significantly affected by dietary state (2.48 +/- 1.0 fold increase in myocardial-to-blood pool ratio in glucose-loaded versus fasted states). Serum glucose, insulin, and free-fatty acid concentrations responded physiologically to glucose loading and fasting but showed no correlation with myocardial 18FDG uptake. PET imaging using 13N-ammonia and 18FDG appears optimal in the glucose-loaded state. PMID- 1869973 TI - Positron tomographic assessment of 16 alpha-[18F] fluoro-17 beta-estradiol uptake in metastatic breast carcinoma. AB - The positron-emitting estrogenic steroid 16 alpha-[18F]fluoro-17 beta-estradiol (FES) has been shown to exhibit selective uptake in primary breast carcinomas; the uptake of tracer by positron emission tomography (PET) is strongly correlated with the tumor estrogen-receptor concentration. We have now extended the use of this radiopharmaceutical for imaging of metastases of breast carcinoma by PET in 16 patients with clinical or radiographic evidence of metastatic disease. Increased uptake of FES was identified on PET images in 53 of 57 metastatic lesions (93%); only two apparent false-positive foci of FES uptake were seen. In seven of the patients, evaluable PET studies were obtained both before and after initiation of antiestrogen therapy. In all cases, there was a decrease in FES uptake in the tumor deposits after initiation of antiestrogen therapy, and the mean (+/- standard deviation) uptake decreased from 2.22 (+/- 1.23) to 0.80 (+/- 0.42) x 10(3)+ dose/ml. These results indicate that PET with FES has high sensitivity and specificity for detecting metastatic breast carcinoma and provide additional confirmatory evidence that the tumor uptake of this ligand is a receptor-mediated process. PMID- 1869974 TI - Assessment of 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone as a positron emitting radiopharmaceutical for the detection of progestin receptors in human breast carcinomas. AB - We have used 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone (FENP) for imaging progestin receptors by PET in patients with primary carcinoma of the breast. In vitro binding and in vivo tissue distribution studies in rats have shown that FENP has high specific activity, high affinity for progestin receptors, and receptor-mediated uptake in target tissues. Eight patients with primary breast carcinoma were studied. Breast carcinoma was identified correctly in 50% of the patients with progestin-receptor-positive tumors; however, the FENP uptake was not correlated with progestin-receptor levels. We noted a low target-to background ratio in humans, with high relative activity in the spine, blood pool, and normal breast tissue. Our findings indicate that FENP is not a suitable agent for imaging progestin receptors in humans. PMID- 1869975 TI - False-negative dipyridamole-thallium-201 myocardial imaging after caffeine infusion. AB - The vasodilator effect of intravenously administered dipyridamole may be caused by an increase in endogenous plasma adenosine levels. We evaluated the effect of caffeine, an adenosine receptor antagonist, on the diagnostic results of dipyridamole-201Tl myocardial imaging in eight patients with coronary artery disease. Caffeine infusion significantly attenuated the dipyridamole-induced fall in blood pressure and the accompanied increase in heart rate. The infusion of dipyridamole alone resulted in chest pain and ST-segment depressions on the electrocardiogram in four patients, whereas none of these problems occurred when the tests were repeated after caffeine. In six of eight patients, caffeine was responsible for false-negative dipyridamole-201Tl tests. Semiquantitive scores of the dipyridamole-induced 201Tl perfusion defects were decreased by caffeine from 9.0 +/- 0.9 to 2.0 +/- 1.1 points (p less than 0.05). Computerized analysis revealed a caffeine-mediated reduction in the percent reversibility of the images from 46% +/- 16% to 6% +/- 10% (p less than 0.05). We conclude that the use of caffeinated products prior to dipyridamole-201Tl testing may be responsible for false-negative findings. PMID- 1869976 TI - Correlation of technetium-99m-DISIDA hepatobiliary studies with biopsies in liver transplant patients. AB - We compared 76 99mTc-DISIDA hepatobiliary studies with corresponding liver biopsies in 36 liver transplant patients to determine the histopathologic abnormalities that corresponded to scintigraphic abnormalities in uptake and excretion. Uptake was judged normal if the cardiac blood pool was barely visible or invisible on the ten minute image. Excretion was judged normal if images subsequent to the 15-min image showed a subjectively normal rate of decreasing parenchymal intensity. Biopsies were graded subjectively for hepatocyte damage and for findings of cholestasis. Uptake criteria were successful in differentiating high from low hepatocyte damage scores (p less than 0.0001), and excretion criteria were successful in differentiating high from low cholestasis scores (p = 0.002), while uptake criteria were not capable of differentiating high from low cholestasis scores, nor were excretion criteria capable of differentiating high from low hepatocyte damage scores (p's greater than 0.05). These results suggest that scintigraphy can distinguish intrahepatic cholestasis from pure hepatocyte damage. PMID- 1869977 TI - Glucose uptake, perfusion, and cell proliferation in head and neck tumors: relation of positron emission tomography to flow cytometry. AB - The uptake of 18F-Deoxyglucose (FDG) was studied in vivo in relation to the proliferation rate of human head and neck tumors. Forty-two patients with histologically proven squamous-cell carcinoma of the head and neck and four patients with metastases of head and neck tumors were examined with PET and FDG prior to surgery. In 35 of these patients, a flow cytometric analysis of the DNA content and the proliferation rate was done using one-dimensional flow cytometry rate was done using one-dimensional flow cytometry (DAPI staining). In 17 cases, perfusion studies with 15O-labeled water were performed. Twenty-seven specimens were evaluable by flow cytometry. The analysis of the distribution of the FDG uptake revealed two groups, showing a high and a lower uptake pattern. In both groups the FDG uptake and the proliferation rate were correlated with an r-value of 0.64 and 0.8 respectively. However, the slope of the regression function was flat. No correlation was found between the perfusion and the proliferation rate. It is suggested that these differences in uptake in histologically identical tumor populations may correspond to differences at the molecular level, e.g., differences in the amount of the glucose carrier, perhaps caused by oncogenic transformation. PMID- 1869978 TI - PET cancer evaluations with FDG. PMID- 1869979 TI - Effect of exercise supplementation on dipyridamole thallium-201 image quality. AB - To determine the effect of different types of exercise supplementation on dipyridamole thallium image quality, 78 patients were prospectively randomized to one of three protocols: dipyridamole infusion alone, dipyridamole supplemented with isometric handgrip, and dipyridamole with low-level treadmill exercise. Heart-to-lung, heart-to-liver, and heart-to-adjacent infradiaphragmatic activity ratios were generated from anterior images acquired immediately following the test. Additionally, heart-to-total infradiaphragmatic activity was graded semiquantitatively. Results showed a significantly higher ratio of heart to subdiaphragmatic activity in the treadmill group as compared with dipyridamole alone (p less than 0.001) and dipyridamole supplemented with isometric handgrip exercise (p less than 0.001). No significant difference was observed between patients receiving the dipyridamole infusion, and dipyridamole supplemented with isometric handgrip exercise. We conclude that low-level treadmill exercise supplementation of dipyridamole infusion is an effective means of improving image quality. Supplementation with isometric handgrip does not improve image quality over dipyridamole alone. PMID- 1869980 TI - Exercise supplementation of dipyridamole for myocardial perfusion imaging. AB - The substitution of intravenous dipyridamole for symptom-limited treadmill exercise has provided a non-invasive means to diagnose coronary artery disease with 201Tl scintigraphy in patients unable to adequately exercise. Limitations of dipyridamole/thallium imaging are primarily due to suboptimal image quality secondary to hepatic tracer concentration and decreased test sensitivity in patients who are dipyridamole "non-responders." Low-level treadmill exercise supplementation improves image quality, whereas handgrip has little, if any, benefit. The effect of low-level exercise in augmenting coronary blood flow is unknown and reports regarding the effect of handgrip are conflicting. The diagnostic benefit of these maneuvers in improving test sensitivity and decreasing the number of "non-responders" has not been documented. The combination of maximal, symptom-limited treadmill exercise and intravenous dipyridamole is a theoretically attractive option to improve overall test sensitivity, but the physiologic consequences and potential side effects should be more thoroughly investigated. PMID- 1869981 TI - Imaging of cocaine-induced global and regional myocardial ischemia. AB - Severe and often fatal cardiac complications have been reported in cocaine users with narrowed coronary arteries caused by atherosclerosis as well as in young adults with normal coronaries. We have found that in normal dogs cocaine induces severe temporary hypoperfusion of the left ventricle as indicated by a significantly lower 201Tl concentration compared to the baseline state. The most significant decrease in uptake occurred 5 min after injection and was more pronounced in the septal and apical segments. Following intravenous administration of cocaine, instead of gradual disappearance of 201Tl from the left ventricle, there was continuous increase in 201Tl concentration in the left ventricle. These imaging experiments indicate that the deleterious effects of cocaine on the heart are probably due to spasm of the coronaries and decreased myocardial perfusion. Since spasm of the large subpericardial vessels does not seem to explain the magnitude of the increased coronary resistance and decreased coronary flow after cocaine as described in the literature, it is suggested that microvascular spasm of smaller vessels plays a major role in the temporary decrease in perfusion. The data may also suggest that severe temporary myocardial ischemia is probably the initiating factor for the cardiac complications induced by cocaine. PMID- 1869982 TI - Synthesis and evaluation of new iodine-125 radiopharmaceuticals as potential tracers for malignant melanoma. AB - The synthesis, labeling, and biodistribution of four 125I radiopharmaceuticals designed to localize in melanoma were tested. Uptake in tumors was demonstrated by autoradiography of whole-body sections and quantitated by measurement of radioactivity of selected tissues and tumors using melanoma-bearing mice. N-(2 diethylaminoethyl)-4-iodobenzamide was selected for its highest melanoma uptake: 60 min after IV injection of 6.5% and 4% ID/g, respectively for murine B16 and human melanotic melanoma. Tumor uptake showed the highest values of all analyzed tissues from 6 to 24 hr after injection. High uptake in melanotic tumor tissue with relatively low uptake in blood, muscle, brain, lung, and liver tissue resulted in high tumor/nontumor ratios (at 24 hr for B16, tumor/blood = 37, tumor/brain = 147, tumor/muscle = 95). This agent was compared with iodoamphetamine. Scintigraphic images of the tumor confirmed that external detection of melanoma is possible with this new radiopharmaceutical. PMID- 1869983 TI - Quantitation of the critically ischemic zone at risk during acute coronary occlusion using PET. AB - Critical myocardial ischemia has been defined experimentally during acute coronary occlusion as flow reduction of 50% or more since cellular ATP depletion begins to occur beyond this flow reduction threshold, placing tissue at risk of cellular injury. To test the hypothesis that critically ischemic fractional left ventricular mass can be measured noninvasively with PET, nine dogs were imaged in a multi-slice positron camera using the perfusion tracer 13N-ammonia, while radiolabeled microspheres were injected into the left atrium during acute coronary occlusion. Images were processed using a 50% threshold and the size of the resulting perfusion defect was expressed as a fraction of total left ventricular image volume. The critically ischemic left ventricular fraction determined in vitro from the microsphere perfusion data, ranged from 5% to 30% of the total left ventricular weight and correlated closely with that determined noninvasively by PET with r = 0.94 (y = 1.05X - 2.0%). We conclude that the fraction of left ventricular myocardium rendered critically ischemic during acute coronary occlusion can be measured accurately and noninvasively in vivo using perfusion imaging with positron emission tomography. PMID- 1869984 TI - PET measurements of hyperthermia-induced suppression of protein synthesis in tumors in relation to effects on tumor growth. AB - Hyperthermia-induced metabolic changes in tumor tissue have been monitored by PET. Uptake of L-[1-11C]tyrosine in rhabdomyosarcoma tissue of Wag/Rij rats was dose-dependently reduced after local hyperthermia treatment at 42, 45, or 47 degrees C. Tumor blood flow, as measured by PET with 13NH3, appeared to be unchanged. The L-[1-11C]tyrosine uptake data were compared to uptake data of L-[1 14C]tyrosine and with data on the incorporation of L-[1-14C]tyrosine into tumor proteins. After intravenous injection, the 14C data were obtained from dissected tumor tissue. Heat-induced inhibition of the incorporation of L-[1-14C]tyrosine into tumor proteins tallied with the L-[1-11C]tyrosine uptake data. Heat-induced inhibition of amino acid uptake in the tumor correlated well with regression of tumor growth. It is concluded that PET using L-[1-11C]tyrosine is eligible for monitoring the effect of hyperthermia on tumor growth. PMID- 1869985 TI - Acute gastrointestinal hemorrhage detected by selective scintigraphic angiography. AB - Intra-arterial 99mTc colloid scintigraphy may have greater sensitivity than either standard intravenous scintigraphy or selective arteriography in detecting gastrointestinal bleeding. Ten millicuries of 99mTc colloid were administered directly into the superior and inferior mesenteric arteries (SMA and IMA) of patients who had undergone selective arterial catheterization for the evaluation of gastrointestinal bleeding. In one patient, 99mTc-albumin colloid was administered directly into the IMA and identified diverticular bleeding. The bleeding had been occult to prior contrast arteriography and refractory to selective intra-arterial Pitressin therapy. In a second patient who had undergone three negative provocative angiograms, selective SMA injection of 99mTc-sulfur colloid identified occult mesenteric varices secondary to portal hypertension. Selective intra-arterial scintigraphy should be valuable in detecting intestinal bleeding occult to conventional studies. This will help in directing further therapy and diagnostic evaluation. PMID- 1869986 TI - Diagnosis of segmental necrosis in a pancreas transplant by thallium-201 perfusion scintigraphy. AB - Thallium-201 was used to image a patient with a pancreatic transplant. Incomplete visualization of the graft on the 201Tl scan, compared to CT, led to the diagnosis of segmental necrosis of the tail of the graft. Due to the low background and favorable target-to-non-target ratio, 201Tl pancreas scintigraphy may be useful in the follow-up of pancreatic transplants. PMID- 1869987 TI - Thallium myocardial scintigraphy in congenitally-corrected transposition of the great arteries. AB - A case of congenitally-corrected transposition of the great arteries is presented with the correlation of thallium scintigraphic results with catheterization data. The essential features of the thallium scintigrams were marked counterclockwise rotation of the heart with perfusion abnormalities of the inferior wall and apex. Since patients with congenitally-corrected transposition of the great arteries may present with the symptom of chest pain, the diagnosis of transposition of the great arteries should be considered in patients with marked counterclockwise rotation of the heart and segmental perfusion abnormalities on thallium scintigraphy. PMID- 1869988 TI - Inflammatory pseudotumor: a gallium-avid mobile mesenteric mass. AB - An 8-yr-old boy with a 1-mo history of culture-negative fever and anemia underwent gallium, ultrasound, and computed tomography studies as part of the evaluation of a fever of unknown origin. These studies revealed a mobile gallium avid solid abdominal mass subsequently proven to be an inflammatory pseudotumor of the mesentery, a rare benign mass. This report documents the gallium-avid nature of this rare lesion and discusses associated characteristic clinical, pathologic, and radiographic features. PMID- 1869989 TI - Severe hypoxemia secondary to acute sternal infarction in sickle cell anemia. AB - This article describes a 28-yr-old black man with sickle cell anemia who presented with severe chest pain secondary to acute infarction of the body of the sternum, hypoventilation, and hypoxemia with no evidence of acute chest syndrome. A bone scan performed 5 days after admission revealed increased uptake in the sternum, suggesting sternal infarction. Repeat bone scan performed 2 mo later demonstrated normal concentration in the sternum. PMID- 1869990 TI - Evolution of technetium-99m-HMPAO SPECT and brain mapping in a patient presenting with echolalia and palilalia. AB - A 78-yr-old woman presented with transient echolalia and palilalia. She had suffered from Parkinson's disease for 2 yr. Routine laboratory examination showed hypotonic hyponatremia, but was otherwise unremarkable. Brain mapping revealed a bifrontal delta focus, more pronounced on the right. Single photon emission computed tomography (SPECT) of the brain with technetium-99m labeled d,l hexamethylpropylene-amine oxime (99mTc-HMPAO), performed during the acute episode showed relative frontoparietal hypoactivity. Brain mapping performed after disappearance of the echolalia and palilalia, which persisted only for 1 day, was normal. By contrast, SPECT findings persisted for more than 3 wk. Features of particular interest in the presented patient are the extensive defects seen on brain SPECT despite the absence of morphologic lesions, the congruent electrophysiologic changes and their temporal relationship with the clinical evolution. PMID- 1869991 TI - No-carrier-added carbon-11-labeled sn-1,2- and sn-1,3-diacylglycerols by [11C]propyl ketene method. AB - This article describes the preparation of sn-1,2-[11C]diacylglycerols and sn-1,3 [11C]diacylglycerols by a no-carrier-added reaction based on a labeling method using [1-11C]propyl ketene, which is one of the most potent acylating agents. [1 11C]Propyl ketene was produced by pyrolytic decomposition of [1-11C]butyric acid and was trapped in pyridine containing L-alpha-palmitoyl-lysophosphatidylcholine, producing L-alpha-palmitoyl-2-[1-11C]butyryl-sn-glycero-3-phosphorylcholine. We adopted an enzymatic reaction to remove the phosphorylcholine, in which L-alpha palmitoyl-2-[1-11C]butyryl-sn-glycero-3-phosphorylcholine was incubated with phospholipase C, hydrolyzing to produce 1-palmitoyl-sn-2-[1-11C]butyrylglycerol. Total synthesis time was about 50 minutes and the specific activity was estimated at 93 GBq/mumol (2.5 Ci/mumol) at end of synthesis. Radiochemical yield was 3.8% based on the trapped 11CO2. sn-1,3-[11C]Diacylglycerol was also synthesized by [1 11C]propyl ketene reaction with 1-palmitoyl-sn-glycerol in a single procedure. The regional brain tissue radioactivities obtained in sn-1,2-[11C]diacylglycerol were higher than those of sn-1,3-[11C]diacylglycerol, and the regional values varied widely. In autoradiography of brain slices from conscious rats, sn-1,2 [11C]diacylglycerol incorporation sites were discretely localized, especially in the amygdala, cerebral cortex, and hippocampus, suggesting that intensive neuronal processing occurred in these areas on the basis of phosphatidylinositol turnover. PMID- 1869992 TI - Endocrine imaging: parathyroid, adrenal cortex and medulla, and other endocrine tumors. Part II. PMID- 1869993 TI - Post-surgical follow-up of differentiated thyroid carcinoma. PMID- 1869994 TI - Ablation dose of iodine-131 for postoperative remnant. PMID- 1869995 TI - A source of toxic gas leakage in a nuclear medicine department. PMID- 1869996 TI - Prevention of metoclopramide-induced akathisia during gastric emptying imaging. PMID- 1869997 TI - Serum thyroglobulin and whole-body iodine-131 scan in the management of differentiated thyroid carcinoma. PMID- 1869998 TI - Constraints on the sensitivity and specificity of "logically" merged test results. PMID- 1869999 TI - A journal's duties: reporting or shaping the news. PMID- 1870000 TI - Administrative prosperity: principle I, Preserving health and vitality. PMID- 1870001 TI - What is important to graduating seniors in selecting their first nursing positions? PMID- 1870002 TI - Variance analysis. Part I, Extending flexible budget variance analysis to acuity. AB - The author reviews the concepts of flexible budget variance analysis, including the price, quantity, and volume variances generated by that technique. He also introduces the concept of acuity variance and provides direction on how such a variance measure can be calculated. Part II in this two-part series on variance analysis will look at how personal computers can be useful in the variance analysis process. PMID- 1870003 TI - The art of negotiation. An everyday experience. AB - The art of negotiation permeates every aspect of one's professional and personal life. Nurse administrators who use a scientific method of negotiation to augment professional judgment and decision making can create a climate conductive to success. The author reviews the definition and purpose of negotiation, examines concepts associated with negotiation and communication, analyzes the steps in the negotiation process, relates the negotiation process to the change process, and describes strategies for conducting effective negotiation. PMID- 1870004 TI - A nurse-managed special care unit. AB - The authors describe the first year of operation of a nurse-managed intensive care unit (ICU). Concerned with the problems, costs, and inadequacies of caring for long-term patients in traditional ICUs, nurse administrators designed a special care unit that incorporates a physical design facilitating family involvement and rehabilitative care, registered nurse case management, and a shared governance management philosophy. Compared with traditional ICUs, the effectiveness of the special care unit is tested in terms of patient and nurse outcomes. Implications of this innovation for health-care delivery systems and the nursing profession are discussed. PMID- 1870005 TI - Management compensation. A reward systems approach. AB - Across the nation, businesses are rethinking the way performance is rewarded. We are witnessing the emergence of newer, more innovative compensation systems. Today's nurse executive is challenged to design systems for management compensation that reward achievement, performance, and contribution. The author describes a reward systems approach to compensation based on contemporary concepts related to pay. PMID- 1870006 TI - Availability of scheduling options important. PMID- 1870007 TI - Improving organizational performance. Administrative nurse specialist. AB - The Executive Nurse Council was challenged to develop strategies designed to empower staff nurses and nurse managers and create opportunities for professional growth. Implementation of these strategies resulted in broad-sweeping changes in roles and functions of groups and individuals at all levels of the organization. The authors describe a support role, administrative nurse specialist, designed to support staff and managers striving to actualize changes in a shared governance framework. PMID- 1870008 TI - JONA'S directory of consultants to nursing administration. PMID- 1870009 TI - Nurses's death from AIDS. PMID- 1870010 TI - Intervertebral disc degeneration. PMID- 1870011 TI - Respiratory cancer among mineral wool workers. PMID- 1870012 TI - Pregnancy outcomes in women potentially exposed to occupational solvents and women working in the electronics industry. AB - Associations of occupational solvent exposure and/or work in electronics production with adverse pregnancy outcomes were examined in a large cross sectional community-based reproductive health study of 1038 California women pregnant between 1980 and 1985. Occupational solvent exposure was determined by two different methods: Bureau of Census codes judged by experts to probably include solvent exposure and self-reported exposure. First trimester solvent exposure classified by either method (n = 52) was significantly associated with spontaneous abortion, adjusted odds ratio 3.34 (95% confidence interval 1.42, 7.81). Among 29 women reporting regular and daily solvent exposure, the adjusted odds ratio increased to 4.44 (95% confidence interval 1.86, 10.58). Work in electronics assembly was significantly associated with delivering a low birth weight infant (adjusted odds ratio 5.38; 95% confidence interval 1.42, 20.46) but was not associated with spontaneous abortions. Further research using biologic monitoring and/or other objective measures of exposure is needed to validate these findings. PMID- 1870013 TI - Occupational physician staffing in large US corporations. AB - Increased provision of occupational health services outside the workplace has been accompanied by signs of change in the quantity and structure of in-house corporate services. The occupational physician:employee ratios of the 25 largest US corporations were compared with each other, with the probable level of hazard as suggested by Bureau of Labor Statistics reports, and with both gross and per capita measures of profitability. We infer that large corporations still employ a disproportionate share of available occupational health expertise. Oil and chemical companies employ the largest number of occupational physicians per capita; computer, electronics, and scientific equipment manufacturers employ the largest number of occupational physicians per capita relative to occupational illness/injury/lost workdays per capita. Tobacco companies employ the fewest occupational physicians by either measure. Corporate profitability explained more than half the variability for the one large within-sector comparison and appeared most related to employment practices for the most-successful and least-successful companies. PMID- 1870014 TI - A study of the hematologic effects of chronic low-level exposure to benzene. AB - A study of 200 persons working with benzene showed no differences in commonly measured hematologic outcomes when compared with 268 nonbenzene workers in the same plant. Exposures ranged from 0.01 ppm to a high of 1.40 ppm 8-hour time weighted average over a 10-year period. Several other factors (age, sex, race, and smoking), however, were associated with these outcomes, indicating the importance of considering confounding factors when comparing hematology results. Exposure to low levels of benzene does not appear to produce an increased level of abnormal hematology measures detectable in routine medical surveillance. PMID- 1870015 TI - Median nerve latencies in poultry processing workers: an approach to resolving the role of industrial "cumulative trauma" in the development of carpal tunnel syndrome. AB - Much attention has been paid recently to a claimed connection between stressful repetitive motion at the work site and the development of carpal tunnel syndrome. Little of this has made its way into the widely appreciated medical literature. To try to discover a reasonable basis for the presence or absence of such an association we measured median nerve motor and sensory latencies in a random sample of employees in a medium industry of the kind thought to be associated with the emergence of carpal tunnel syndrome. A control group made up of applicants for positions of this sort was used. No association between employment experience and the development of slowing of the median motor latency was encountered in any group. No association was discovered for sensory latencies for men or for the left hands of women. A small association was discovered for the sensory latency in right hands of long-term female employees. This was similar in magnitude to the increased risk of prolongation associated with aging. Our data provide very little evidence for the concept of cumulative trauma as a prominent cause of carpal tunnel syndrome in American industry. These results are discussed in light of the recent Australian false epidemic of repetition strain injury. PMID- 1870016 TI - Mortality among workers exposed to external ionizing radiation at a nuclear facility in Ohio. AB - In a cohort mortality study of white men employed by the Mound Facility (1947 through 1979), observed deaths did not exceed those expected based on US death rates for the overall cohort or for the subcohort monitored for external ionizing radiation. Among the radiation-monitored subcohort, mortality for workers with cumulative radiation doses of at least 10 mSv was not significantly increased when compared with mortality for coworkers with cumulative doses of less than 10 mSv. A significant dose-response based on a Mantel-Haenszel test of trend was observed for all leukemias. However, when a death from chronic lymphatic leukemia, a type of leukemia generally not regarded as radiogenic, was removed from the analyses, the strength of the dose-response was reduced. PMID- 1870017 TI - Pulmonary alveolar proteinosis: a possible sequel of NO2 exposure. AB - Pulmonary alveolar proteinosis was diagnosed via bronchoscopy in a patient. There was no previous history of inhalation dust exposure. NO2 has been implicated in pulmonary alveolar proteinosis development in animal models. In this case, the diffusion capacity was a sensitive indicator of the disease process. PMID- 1870018 TI - Cumulative trauma disorders of the upper extremity. A preventive strategy is needed. PMID- 1870019 TI - What are cumulative trauma disorders? PMID- 1870020 TI - Occupational eye injuries in soldiers. AB - Soldiers have occupational exposure to eye hazards that in many ways are comparable to those in civilian industry. We conducted a prospective, community based, case-control study at three large troop installations of an infantry division to characterize nonmilitary-unique, occupational eye injuries and associated risk factors and to assess current occupational health practice in eye injury prevention in the division. The findings indicate that the most important risk factors are youth, a history of an eye injury in the preceding two years, and, paradoxically, the perception that supervisors are concerned and well informed about eye injury prevention. Injury severities were mild resulting in an average of 1 day of lost employment per injury. The economic impact for the entire US Army Europe is estimated to approximate $1,100,000 per year. PMID- 1870021 TI - Drug screening in the workplace: ethical guidelines. PMID- 1870022 TI - Managing cholesterol in children and adolescents. AB - Reduction of elevated cholesterol in adults decreases risk of coronary heart disease. Despite evidence of atherosclerosis development at early ages and studies confirming cholesterol tracking from childhood into adulthood, many physicians are reluctant to screen for hypercholesterolemia in children and adolescents. Targeting screening only to children of high-risk families fails to identify as many as two-thirds of at-risk children. Dietary modification and medical therapy appears safe and effective in this age group. Recommendations for screening of all children by age 5 are made, with guidelines for managing elevated cholesterol. PMID- 1870023 TI - Lay midwives in Oklahoma. AB - Since the 1970s a trend towards home birth has sparked a strident debate among obstetric practices and lay midwives which concerns the most valuable member of our society: newborn infants. This paper focuses specifically on lay midwives. Their situation in the country as a whole and in Oklahoma in particular is discussed. The state has ignored the existence of these practitioners, forcing the medical establishment to deal with the consequences of unsafe deliveries. PMID- 1870024 TI - The new role of the nursing home medical director. PMID- 1870025 TI - On physicians and litigation. AB - Because litigation involving physicians has come to influence the practice of medicine in several ways, we describe many of the legal processes involved. We also offer specific advice in regard to steps which can be effectively taken, and those which should be avoided. We close with a plea for active participation by physicians in the judicial process and in the promulgation of appropriate legislation. PMID- 1870026 TI - Leaders in medicine. C.S. Lewis, Jr., MD. PMID- 1870027 TI - Telemeterized in vivo hip joint force data: a report on two patients after total hip surgery. AB - Two telemeterized femoral components were implanted in two patients as part of normal total hip replacement procedures. The two components were instrumented to measure the three force components directed along: (a) the neck axis, (b) transverse to the neck axis and in the plane of the prosthesis, and (c) transverse to the neck axis and perpendicular to the plane of the prosthesis. Data were collected at multiple sessions during the early postoperative period for a number of standard activities, including gait, stair climbing, rising from a chair, single leg stance, double leg stance, ipsilateral and contralateral straight leg lifts while supine, ipsilateral flexion and extension while standing, and ipsilateral abduction while standing and lying on the contralateral side. These data are summarized and compared with the published results from analytic studies and with the results from previous studies using instrumented femoral components. Peak loads for gait during the period of study were roughly 2.7 body weights (BW) when the patients walked at their normal pace. Contact forces at the hip during stationary single leg stance approximated the peak loads during gait with values ranging from 2.1 to 2.8 BW. The highest forces recorded reached values approaching 5.5 BW and occurred during periods of instability while the patient engaged in stationary single leg stance. Our in vivo data indicate that forces generated during the above activities increase in magnitude quite rapidly during the early postoperative period and that during this period the patients have the ability to perform the activities of daily living without generating the high amplitude joint contact forces suggested by the results of dynamic studies. Joint contact forces during gait were found to depend on speed, but the high absolute magnitudes predicted by model studies were not supported by the in vivo data. PMID- 1870028 TI - Pattern of bone loss of the proximal femur: a radiologic, densitometric, and histomorphometric study. AB - The pattern of bone loss in the proximal femur was studied in 141 cadaveric femora from 36 women and 39 men ranging from 27 to 89 years of age. Bone mineral density (BMD) of the femoral neck, greater trochanter, Ward's triangle, and tensile and compressive stress regions were measured by dual photon absorptiometry. Radiographs were graded by Singh's method. Histomorphometry of tensile and compressive trabecular areas was performed on ground midsection of the methylmethacrylate-embedded whole proximal femur. Although Singh index had some correlation with BMD of the femoral neck, the various BMD measurements showed that all regions lost bone to the same extent; in particular, no selective bone loss was found at low stress regions (tensile trabeculae or Ward's triangle). Histomorphometry revealed that most of the trabecular bone loss of the proximal femur is attributable to a decrease in thickness of individual trabeculae. PMID- 1870029 TI - Mesenchymal stem cells. AB - Bone and cartilage formation in the embryo and repair and turnover in the adult involve the progeny of a small number of cells called mesenchymal stem cells. These cells divide, and their progeny become committed to a specific and distinctive phenotypic pathway, a lineage with discrete steps and, finally, end stage cells involved with fabrication of a unique tissue type, e.g., cartilage or bone. Local cuing (extrinsic factors) and the genomic potential (intrinsic factors) interact at each lineage step to control the rate and characteristic phenotype of the cells in the emerging tissue. The study of these mesenchymal stem cells, whether isolated from embryos or adults, provides the basis for the emergence of a new therapeutic technology of self-cell repair. The isolation, mitotic expansion, and site-directed delivery of autologous stem cells can govern the rapid and specific repair of skeletal tissues. PMID- 1870030 TI - Proteoglycan alterations during developing experimental osteoarthritis in a novel hip joint model. AB - Degenerative hip joint disease was induced in dogs by extra-articular surgery that created a condition that mimics hip dysplasia. Decreased acetabular coverage of the femoral head gave altered mechanical load, with ensuing cartilage degeneration. For comparison, degenerative knee joint disease was induced in other dogs by transection of the anterior cruciate ligament of the knee. The femoral head articular cartilage showed macroscopic signs of degeneration within a month. No macroscopical changes of synovitis were present. Chemical analysis of cartilage samples showed loss of proteoglycans. Guanidine hydrochloride extracts of the cartilage contained proteoglycan fragments that could be separated by equilibrium density gradient centrifugation in cesium chloride. The data indicate that proteoglycans are fragmented by proteolytic cleavage and lost from the cartilage. The proteoglycans remaining in the tissue are smaller and have lost the ability to aggregate with hyaluronic acid. Similarly, in experimental knee joint osteoarthritis, the proteoglycan content of the cartilage decreased. The structural changes of those proteoglycans remaining were of a different nature, with no changes in proteoglycan size or aggregation properties, possibly indicating that both degradation and repair took place in the knee articular cartilage and/or that fragments were rapidly lost from the tissue. This may follow from different surgical procedures, only the one used for the hip joint being extra-articular, or from the different anatomy and physiology of the hip joint and the knee joint. PMID- 1870031 TI - Evaluation of orthogonal mechanical properties and density of human trabecular bone from the major metaphyseal regions with materials testing and computed tomography. AB - We evaluated the orthogonal mechanical properties of human trabecular bone from the major metaphyseal regions with materials testing and quantitative computed tomography (CT). The proximal tibia, distal femur, proximal femur, distal radius, and proximal humerus from fresh cadaver specimens between the ages of 55 and 70 years were excised and prepared for experimentation. The bones were embedded and scanned at 1 or 1.5 mm intervals on a Technicare HPS 1440 and GE 9800 CT scanner. After scanning, the bones were sectioned, producing 8-mm cubes of trabecular bone which were mechanically tested in uniaxial compression at a strain rate of 1%. The testing sequence consisted of preyield tests in two of the three orthogonal directions and failure in the third. After testing, the cubes were evaluated for apparent density and ash weight. The results of the study show that the strength and stiffness of trabecular bone varies significantly within metaphyseal regions and from metaphysis to metaphysis. The power and significance of relationships between density and modulus varied as a function of metaphyseal location. Both linear and nonlinear models were significant, suggesting that trabecular deformation occurs in response to both axial and bending loads. Finally, the need for architectural measures of trabecular bone to predict mechanical properties is emphasized. PMID- 1870032 TI - Electrokinetic behavior of intact wet bone: compartmental model. AB - Streaming potential experiments were performed on chemically-treated intact wet bone plugs equilibrated in potential-determining ion buffers. Comparison of calculated zeta (zeta) potentials from intact wet bone streaming potentials and bone particle electrophoresis indicates different values. Intact streaming potential experiments, where fluid is forced through the samples, represents flow, primarily through the vascular channel system, and contribution of the organically-lined channels to the electrokinetic zeta potential. Bone particle electrophoresis represents mainly the electrokinetic contribution of exposed mineralized matrix. The organic linings present in the vascular channel system limit potential-determining ions' access to the mineralized matrix. These linings may have an important role in mineral homeostasis and control of ion fluxes between bone compartments. PMID- 1870033 TI - Human carpal ligament recruitment and three-dimensional carpal motion. AB - In five fresh human cadaver wrist joints six carpal ligaments and seven carpal bones were marked with small, radio-opaque pellets. Using a roentgenstereophotogrammetric measuring system, the ligamentous length changes and the kinematics of carpal bones were determined in different flexion and deviation positions of the hand. The data generated by this method differ significantly from lengthening data predicted by current concepts on carpal ligament functioning. The motions of carpal bones and the lengthening of the carpal ligaments were related to each other. It appeared that most carpal ligaments lengthen only during one half of a full movement cycle. Hence, ligaments seem to constrain either a dorsal- or a palmar-directed motion of the hand, or an ulnar- or a radial-directed motion of the hand. When the hand is in maximal radial deviation or maximal palmar flexion, none of the ligaments has a greater length than in the neutral situation. The tested parts of the lunatotriquetrum palmar ligament do not lengthen during any movement of the hand. Significant lengthening relative to the neutral situation was found for the radiocapitate palmar ligament (6.5% in maximal ulnar deviation and 11.7% in maximal dorsal flexion of the hand), and for the distal string of the radiolunate palmar ligament (6.4% in maximal ulnar deviation). It was confirmed that the carpals, apart from moving in the plane in which the hand motion takes place, also execute considerable out-of-plane motions during hand motions. The combination of these experimentally and simultaneously determined data on length change and on the movements of carpal bones are found to be necessary in order to give suitable explanations for the observed separate kinematical phenomena. PMID- 1870034 TI - The effects of frequency and duration of controlled passive mobilization on tendon healing. AB - This study was designed to determine the effects of frequency and duration of controlled passive motion on the healing flexor tendon following primary repair. Adult mongrel dogs were divided into two groups based on frequency of controlled passive motion. In one group, motion was applied manually at a frequency of 12 cycles/min for 5 min/day; in the other group, a continuous passive motion machine was used to apply motion at a lower frequency of 1 cycle/min for 60 min/day, making the number of cycles each day for both groups identical. Gliding function and tensile properties of repaired tendons were evaluated biomechanically at 3 and 6 weeks postoperatively. Results showed that gliding function in both groups was similar, but tensile properties, as represented by linear slope, ultimate load, and energy absorption, were significantly improved in the higher frequency group. It was concluded that frequency of controlled passive motion rehabilitation is a significant factor in accelerating the healing response following tendon repair, and higher frequency-controlled passive motion has a beneficial effect. PMID- 1870035 TI - Ascorbic acid requirement for optimal flexor tendon repair in vitro. AB - Numerous studies from our laboratory have defined aspects of the repair process in a lacerated flexor tendon model, both in vivo and in vitro. Inherent in the development of a viable tissue or cell culture model system is the definition of the optimal media environment. Since our laboratory investigations of in vitro flexor tendon repair encompass the formation of numerous extracellular matrix proteins, we have defined the optimal level of ascorbic acid with which to study the tendon wound healing process. The ascorbic acid requirement for proline and lysine hydroxylase activity during collagen biosynthesis is well known, and the importance of this vitamin for matrix proteoglycan synthesis more recently has been appreciated. This report describes the effect of several levels of ascorbic acid on 3H-thymidine incorporation, collagen and noncollagen protein synthesis, and glucose utilization and lactate production. Profundus flexor tendon segments were obtained from young adult New Zealand white rabbits and maintained in organ culture for periods of 1, 2, or 3 weeks. Ascorbic acid concentrations ranged from 50 to 300 micrograms/ml and were added fresh at each 48-h media change. Tendon protein synthesis, glucose metabolism, and cell permeability/viability were significantly correlated with the level of ascorbic acid in the culture medium. The results suggest that ascorbic acid levels in excess of the traditional 50 micrograms/ml are necessary to optimally maintain flexor tendons from adult animals in organ culture with 48-h media and ascorbate changes. Additionally, it may be necessary to determine the precise ascorbic acid requirement for individual tissues, since the specific tissue/cell and species requirement for ascorbate may vary. PMID- 1870036 TI - Are leg electromyogram profiles symmetrical? AB - Electromyographic (EMG) patterns reflect function of the neuromuscular system. Abnormality of a given pattern may be established by comparison with that of the contralateral (presumably normal) limb if one ensures a difference beyond normal degrees of symmetry. We studied EMG patterns in six homologous knee muscles during freely selected, slow, and fast gaits in normal subjects. EMG signals were electronically conditioned to produce linear envelopes; envelopes from at least eight cycles from each subject at each speed were ensemble averaged. Grand ensemble averages for each muscle and speed were assembled from all subjects for right and left muscles. Transformed correlation coefficients (r') and variance ratios established the degree of similarity. All muscles exhibited a fair degree of symmetry (mean r' = 0.797-0.953), but we saw exceptions. On rare occasion, muscles repeatedly exhibited monophasic signals on one side and biphasic on the other. With increasing speed, signals generally became more repeatable, but we occasionally saw monophasic patterns becoming biphasic or vice versa. Considerable caution is essential before presuming any given pattern is abnormal. To ensure that a given pattern is abnormal one could establish that the pattern lies outside some statistical limits for normal population patterns controlled for speed and outside statistical limits for normal symmetry. Alternatively, one could determine the level of statistical differences in EMG patterns associated with distinct differences in level of functional performance between normal subjects and patients. PMID- 1870037 TI - Measurement reproducibility of two commercial knee test devices. AB - Objective evaluation of patients' knee motion using mechanical devices, whether for diagnostic purposes or for assessing rehabilitative procedures, requires that these devices be reproducible, in order to avoid errors independent of the patients' condition. This study prospectively evaluates the reproducibility of two commercial knee test systems, the KT 1000 Knee Ligament Arthrometer and the Genucom Knee Analysis System, by performing repeated measurements on twenty normal men. Average knee motion, between-subject variance, and within-subject variance were determined by performing repeat tests on the same day and one week later. No significant difference was found between measurements taken on the two different test days, but the within-subject variation was high. We found that larger applied forces or moments resulted in a larger variation in mean displacements. However, the percent variation about the mean (coefficient of variation) decreased with increasing applied loads. The coefficient of variation for the KT 1000 varied from 8 to 33% and for the Genucom, from 13 to 87%. On an individual basis, large variations were found in repeated measures for both devices. To minimize errors, we recommend that repeated tests be performed, higher forces and moments utilized, and specific flexion angles be used for each device and test. Even under these conditions, caution must be exercised when evaluating individual subjects. PMID- 1870038 TI - Alterations in femoral and acetabular bone strains immediately following cementless total hip arthroplasty: an in vitro canine study. AB - Alterations in strain patterns in both the femur and acetabulum of the dog, due to cementless total hip arthroplasty (THA), were evaluated by monitoring cortical bone strains before and immediately following implantation of components, using an accurate in vitro jig, simulating the loading of the canine hip in vivo. Femoral arthroplasty with straight stem, canal-filling, femoral components, made of titanium-based alloy, led to a statistically significant reduction of proximal femoral bone strains, with proximal medical compressive strains reduced, on average, to only 22% of intact strain magnitude (p less than 0.01), even though the prostheses contained collars and were not fixed with cement. Strain alterations on the acetabulum, following cementless THA, were more complex and variable. Laterally, a significant decrease (p less than 0.01) in periacetabular strains to between 20 and 60% of the intact state was observed, while medial wall strains varied inconsistently after arthroplasty. These strain alterations reflect major changes in mechanical loading of both the femur and acetabulum immediately following cementless THA, using components similar to those used clinically in humans. Major reductions in strains on the proximal femur occurred with cementless femoral components, while the change in strains on the acetabulum were variable, and could be a result of variations in fit and placement of components inherent even in well-controlled implantation techniques. The physiologic in vitro loading of the canine femur with the pelvis, used to obtain these data, can be applied to future investigations exploring stress transfer around uncemented components and the relationship of stress transfer to morphological changes of bone, in the canine model. PMID- 1870039 TI - An evaluation of three loading configurations for the in vitro testing of femoral strains in total hip arthroplasty. AB - Despite recent advances in total hip arthroplasty, proximal femoral resorption and osteopenia remain problems. To analyze the proximal strain effects of three different loading conditions, strains produced in intact and postarthroplasty femora have been compared. Ten adult cadaveric femora of similar size, shape, and rigidity were tested. Ten strain-gauge rosettes were positioned on each femur. To simulate the "single leg support" phase of gait, fixtures were developed to load the femora under three different configuration: the VS (vertical shaft) configuration, with a vertically orientated femur having rotational freedom proximally and distally; the ITB (iliotibial band) configuration of a femur with rotational freedom positioned 11 degrees from the vertical, with a strain-gauge adjustable metallic simulation of the lateral muscles of the thigh; and the ABD (abductor) configuration of a femur with rotational freedom positioned 11 degrees from the vertical, with a strain-gauge adjustable metallic simulation of the abductor muscles. Each femur was loaded less than or equal to 600 N through the medial point, located at one sixth of the transcondylar distance. Strain patterns and magnitudes produced by the three loading configurations were quite different in both the intact and postarthroplasty femora. Both the ITB and the ABD configurations resulted in greater proximal medial compression and lateral tension than did the VS configuration. The magnitudes of the proximal strains were significantly greater in the ABD configuration (p less than 0.05). Postarthroplasty femora showed similar proximal results. It is proposed that meaningful strain data for the physiologically loaded femur can be obtained only with simulations that include the forces produced by the iliotibial band. To overcome the indeterminate nature and biological variation in these forces, the studies have to consider a range of forces. PMID- 1870040 TI - The biologic effects of implant materials. AB - The interaction between implant materials and the surrounding biological environment continues to be an area of intense research and clinical interest. This article presents the information presented in a symposium, held during the 36th Annual Meeting of the Orthopaedic Research Society, in which several important issues concerning the biologic effects of implant materials were discussed. These issues included the mechanisms by which implant materials are released to the surrounding tissues and the ways in which these tissues respond to implant materials. The problem of bone loss around cementless implants was discussed as a specific example of a biologic effect resulting in both bone remodelling and endosteal erosion. PMID- 1870041 TI - Hypodermoclysis in dehydrated elderly patients: local effects with and without hyaluronidase. AB - Dehydration is frequently encountered in elderly patients and hypodermoclysis is an alternative method of parenteral rehydration. Hyaluronidase is classically added to the solution infused subcutaneously. The local effects of hypodermoclysis with or without hyaluronidase were investigated by using a randomized double-blind study in 12 dehydrated elderly patients. Five hundred millilitres of a 5% glucose saline solution was infused subcutaneously in 2 hours in each thigh, (A) with and (B) without 250 U of hyaluronidase. Circumference and temperature of each thigh were assessed before and after the infusion. Color was evaluated after the infusion. The gain in thigh circumference was less in the presence of hyaluronidase, but the other variables did not differ. The patients were thoroughly questioned about pain: no difference was noted between solutions A and B. We conclude that hyaluronidase adds no comfort that justifies its systematic use in the hypodermoclysis of glucose saline solutions. PMID- 1870042 TI - Common symptoms in patients with advanced cancer. AB - The goal of this study was to identify the symptoms of patients with advanced cancer. One hundred consecutive patients referred to the Palliative Care Service at the Cleveland Clinic Foundation were studied using a standard tool that included questions on 38 specific symptoms. The most common symptoms were pain, weight loss, and anorexia. Significant findings also included that women had more frequent and severe gastrointestinal complaints than men. These do not appear to be related to specific cancer primary sites. PMID- 1870043 TI - Death late in the 20th century. PMID- 1870044 TI - Who should be the medical director of a hospice program? PMID- 1870045 TI - Neuropathic cancer-related pain. PMID- 1870046 TI - When suffering is unbearable: physicians, assisted suicide, and euthanasia. PMID- 1870047 TI - A review of the etiology, diagnostic techniques and management of IUGR, and the clinical application of Doppler in the assessment of placental blood flow. PMID- 1870048 TI - Measurement of head compression during labor: preliminary results. AB - To study the pressure to which the fetal head is exposed during the second stage of labor, an instrument was designed to measure continuously the pressure between the presenting part and the birth canal on both sides of the fetal head. Pressure parameters during and between the uterine contractions were calculated from 42 spontaneous vertex deliveries presenting as occiput anterior. During the second stage the overall average of the mean maximum head pressure during uterine contraction was 31.8 +/- 11.0 kPa, that of the mean head pressure measured 13.3 +/- 4.8 kPa during uterine contraction and 5.5 +/- 3.7 kPa during the interval between contractions. The pressure on the fetal head was about twice as high as the amniotic pressure. It increased towards the end of labor. The objective measurement of fetal head pressure is the prerequisite in the study of the relationship between birth-related injuries and excessive head compression during parturition. PMID- 1870049 TI - The implication of upright posture on pregnancy. AB - Pregnant women spend more than half of the day in an upright position. The physiological effects of this posture on the mother and the fetus are evaluated. Changes in vascular autoregulation and anatomy lead to maternal fainting in about 8% of women during early pregnancy. The immediate effects of such episodes on the fetus are unknown. There is a positive correlation of orthostatic dysregulations and abortions. In late pregnancy we found a significant increase in functional residual capacity in the upright posture. Minute volume and oxygen consumption were also significantly increase (p less than 0.001). Regarding the cardiovascular changes we detected a rhythmic change of the maternal heart rate with the change to upright position, which had not been published before. Change from the left lateral position to unsupported standing increased maternal heart rate by a mean of 27 beats per minute and a mean duration of 105 seconds in two thirds of the women. This was accompanied by a decreased cardiac output, systolic blood pressure and an increased oxygen consumption. The gravid uterus is responsible for these changes. During the upright position, the venous flow to the right ventricle is inhibited by the relaxed uterus. Contractions, leaning forward and the muscle pump improve the venous return. The phenomenon reached its maximum during the 38th week, where 71% of pregnant women displayed a cyclic change in heart rate. The fetal heart rate baseline is significantly increased in the upright position with a significantly reduced acceleration frequency (p less than 0.001). Combined with the data from epidemiologic studies, prolonged standing during late pregnancy may signal potential risks for the fetus such as low birth weight, prematurity and stillbirths because of an 'uterovascular syndrome'. Maternal standing possibly may be used as a physiological fetal stress test. PMID- 1870050 TI - No difference between home and clinic blood pressure measurements in pregnancy: a computerized telemetric study. AB - Many decisions in pregnancy are based on one or two casual blood pressure estimations made in the antenatal clinic. No previous study has challenged the validity of this practice or attempted to discover whether there are significant differences between the blood pressures of pregnant women when they are measured in the clinic and when they are measured in their home environment. We measured the blood pressures of 35 healthy pregnant women both at the antenatal clinic and in their own homes. All the women were at between 28 and 32 weeks gestation. At both locations, ten consecutive blood pressure and pulse measurements were made at one minute intervals using a Dinamap 1846P automated blood pressure monitor. The readings taken in the clinic were supervised, whilst at home the patients used our blood pressure telemetry system without direct supervision, the results being transmitted automatically to the hospital computer via the public telephone network. The Dinamap results were analysed in detail. Each ten minute recording session was summarised in terms of the first, last, highest, lowest and mean of the systolic, diastolic and mean arterial blood pressure, and pulse measurements in that session. Also, two measures of the variability within a ten measurement series were considered, the average change in pressure or pulse from one reading to the next, and the difference between the highest and lowest readings of pressure and pulse in the series. All descriptors of the clinic and the home measurements were compared using the paired Student's t-test. Clinic and home blood pressure measurements were not significantly different from each other in any respect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870051 TI - Validity of umbilical artery blood velocimetry in the prediction of intrauterine growth retardation and fetal compromise. AB - In a prospective longitudinal investigation, the validity of umbilical artery velocimetry in the detection of IUGR and fetal compromise was calculated in a group of 105 patients. With the help of pulsed Doppler ultrasound, measurements were performed from a menstrual age of 15 weeks onwards till term. The pulsatility index was calculated. The sensitivity, specificity, likelihood ratio and post test probability were determined with regard to the ability to predict IUGR and fetal compromise. The sensitivity in the detection of IUGR was 44.4%, the post test probability was 32.4%. For the prediction of fetal distress a sensitivity of 77.8% and a post test probability of 40.1% was calculated. In a selected group of high-risk patients (IUGR or PIH) the post-test probability was 77.6%. It seems clear that umbilical artery velocimetry is not useful as a screening tool for IUGR, but it has some potential to predict fetal distress. PMID- 1870052 TI - Doppler investigation of the fetal circulation. AB - Doppler ultrasound provides a non-invasive method for the study of fetal haemodynamics. Animal studies on effects of hypoxia have provided evidence of a redistribution of cardiac output to favour perfusion of the fetal heart, adrenals and brain, at the expense of the carcass, gut and kidneys. This paper summarises the changes in fetal Doppler parameters with advancing gestation. Furthermore, it examines the alterations in fetal haemodynamics in relation to fetal blood oxygen tension in samples obtained by cordocentesis from small for gestational age (SGA) fetuses. In SGA fetuses increased downstream impedence to flow in the umbilical artery, as demonstrated by the absence of end-diastolic frequencies in the flow velocity waveforms (FVW), is associated with fetal hypoxia. This presumably reflects the underlying derangement of placental structure and function. The impedence to flow and mean blood velocity were also measured in FVWs from the descending thoracic aorta and common carotid artery, obtained by pulsed Doppler ultrasound, and from the middle cerebral and renal arteries obtained by colour flow imaging. There were significant correlations between the degree of fetal hypoxia and alterations in Doppler parameters, which were compatible with the brain sparing effect. Thus, in fetal hypoxia impedence to flow in the common carotid and middle cerebral arteries was decreased, whereas impedence in the aorta and renal artery was increased. There were simultaneous alterations in the mean blood velocity in the opposite direction to those in impedence. PMID- 1870053 TI - Color Doppler flow mapping of fetal heart. AB - Color Doppler flow mapping of fetal heart was performed in 582 fetuses between 16 and 38 weeks of gestation. Congenital heart diseases were excluded in 522 fetuses correctly. In 59 fetuses structural and/or functional cardiac abnormalities were diagnosed. In one fetus small multiple ventricular septal defects were missed. The most important additional information obtained by color Doppler flow mapping was: (1) Diagnosis of insufficiencies of atrioventricular valves; (2) Demonstration of turbulent high velocity jet in stenosis of semilunar valve; (3) Reverse flow in ascending aorta in atresia of aortic valves and on ductus arteriosus and main pulmonary artery in atresia of pulmonary valves; (4) Reverse perfusion of ductus arteriosus and main pulmonary artery as well as an antegrade turbulent high velocity jet in severe pulmonary stenosis as part of tetralogy of Fallot; (5) Bidirectional interventricular shunting of blood in ventricular septal defect. Color Doppler flow mapping allows rapid screening for flow abnormalities of the fetal heart. Exact localisation of sample volume by pulsed wave Doppler in area of abnormal flow pattern is possible, thus significantly reducing the Doppler examination time. The accuracy of prenatal diagnosis of congenital heart diseases is improved by application of color Doppler flow mapping, in particular in presence of complex cardiac defects. PMID- 1870054 TI - Critical analysis of the validity of electronic fetal monitoring. AB - The validity of the diagnosis fetal distress based on electronic fetal monitoring (EFM) is low. It can be argued that the prediction of fetal distress may be influenced by the obstetric intervention, and a number of false-positive (FP) decisions are in fact cases of successful prevention of acidosis. The false negative decisions (FN) may include cases in which an operative delivery was not performed, although the impaired fetal condition was correctly recognized. To estimated the magnitude of these effects, deliveries after 28 weeks of gestation, in which EFM was applied, were studied. The medical staff involved in these deliveries was asked to estimate the umbilical artery pH immediately before birth. After birth the pH was measured. Cases were classified as operative delivery for fetal distress or other. Fetal distress was supposes to be confirmed if the umbilical artery pH was less than or equal to 7.14. Pre-birth estimates of the pH were obtained in 393 cases. Of the 20 FP cases, 70% were real FP after considering the prebirth estimate; of the 35 FN cases, 89% were real FN. After correction for mistaken false results the sensitivity increased from 20.5% to 29.5% and the predictive value from 31.0% to 51.7%. Although validity and predictive values improve after correcting for the mistaken false results, their values are still unsatisfactorily low. PMID- 1870055 TI - The advantages of computerized fetal heart rate analysis. AB - A brief account is given of the advantages of computerized analysis of human fetal heart rate (FHR) traces antenatally, based on clinical use over 8 years. Accuracy is greater. Results are presented quantitatively and consistently. The numerical measures of the FHR pattern are related to other objective measures of fetal health, e.g. initial compensated hypoxaemia or terminal acidaemia. Computerized analysis has shown that changes in FHR variation are a better guide than the presence or absence of large decelerations. Recording time is used better. Synoptic displays of data over 4 weeks show significant trends in fetal heart rate variation and movements with time. And the problems generated by the limitations of fetal heart rate monitors are identified to exclude spurious information. PMID- 1870056 TI - System 8000: computerized antenatal FHR analysis. AB - SYSTEM 8000 is a computerized system for antenatal fetal heart rate (FHR) analysis, with interaction online to ensure good quality recording and to minimize the time required to obtain the necessary information (based on fetal movements and tocodynamometer readings as well as FHR). The equipment consists of a Personal Computer with hard disk, interfaced to a fetal monitor. Software is written in C. An extensive definition is given on most of the functions and parameters as calculated by the system, e.g. record quality, uterine contraction peaks, basal heart rate, variation, decelerations and accelerations. System 8000 is designed to take account of the episodic changes in FHR and fetal movements characteristic of sleep states. Their presence naturally affects the mean FHR variation calculated over, say 20-30 mins. But, as the amplitude of these episodes is attenuated in association with growth retardation and hypoxaemia, the measurements of variation decline. In practice inter- and intra-observer variation is greatest in assessing FHR variation. Yet a decrease in variation is the most reliable index of fetal deterioration. The system measures FHR variation accurately and reproducibly, as well as fetal movements. In the synoptic display these two equally important fetal variables are given their rightful prominence. It has been interesting to observe how rarely the basal FHR changes in fetuses suffering progressive respiratory insufficiency, and how extreme tachycardia (a basal rate greater than 170/min) tends to reflect other fetal problems such as infection or maternal pyrexia. PMID- 1870057 TI - Computer-assisted analysis of normal second trimester fetal heart rate patterns. AB - A software package for computer-assisted analysis of antenatal fetal heart rate (FHR) patterns has been commercially available from 1989. Reference ranges for the third trimester of pregnancy have been established. In order to obtain reference values for the second trimester, one hour FHR recordings were made between 20 and 29 weeks gestation in 77 women with uncomplicated pregnancies. There was a significant increase of (medium term) FHR variation and of the number of accelerations from 20 to 29 weeks (r = 0.48, p less than 0.01 and r = 0.34, p less than 0.01 respectively). The lower limit of normal FHR variation (mean--2 SD's) increased from 18 msec at 20 weeks to 28 msec at 28 weeks. Furthermore, a 30 minute recording appeared to be sufficient to obtain a reliable impression of FHR variation. Short term FHR variation, a measure of FHR variation that facilitates the identification of sinusoidal FHR patterns, also increased significantly between 20 and 29 weeks (r = 0.61, p less than 0.01). Delerations (greater than 20 beats/min and greater than or equal to 30 seconds) were present in 54% of the recordings and are a more or less common phenomenon at this age. It is concluded that during the second trimester FHR variation differs considerably from that in the third trimester. This should be taken into account in the interpretation of second trimester FHR records. PMID- 1870058 TI - The Porto system for automated cardiotocographic signal analysis. AB - Cardiotocography (CTG) lacks reliability and reproducibility and these problems are believed to be overcome by computer analysis. In this article we describe a system developed for routine clinical automated CTG analysis based on a low cost personal computer. Presently the system has processed 70 ten minute tracings. Fetal heart rate baseline, acceleration--deceleration detection, and long term variability estimation were performed in a satisfactory way. PMID- 1870059 TI - Longitudinal assessment of behavioural transitions in healthy human fetuses during the third trimester of pregnancy. AB - A longitudinal study was performed on 35 healthy fetuses in order to evaluate the developmental course of behavioural transitions during the last trimester of pregnancy. A progressive decrease in the duration of transitions as a function of gestational age was evidenced for both transitions from 1F to 2F and transitions from 2F to 1F. Concerning the sequence in change of behavioural variables (fetal heart rate, fetal eye movements and fetal gross body movements) a random distribution was found until 30 weeks for 1F to 2F transitions and until 34 weeks for 2F-1F transitions. After these gestational ages fetal heart rate and fetal gross body movements respectively become the first variable to change during 1F 2F and 2F-1F transitions. Reference values for these parameters are calculated in order to provide a basis for the diagnosis of behavioural abnormalities in high risk fetuses. PMID- 1870060 TI - Duration, amplitude and shape of accelerations in relation to fetal body movements in behavioral state 2F. AB - The relationship between fetal movements and fetal heart rate accelerations was analyzed in 34 healthy near term fetuses. Periods of coincidence 2F (C2F) with a mean duration of 34 +/- 6 minutes per fetus were selected, with a total of 463 accelerations. Nineteen percent of single body movements and 71% of compilations of movements were accompanied by an acceleration. The minimal duration of single movements associated with accelerations was 4-5 seconds. Movements with associated accelerations differed significantly in duration from movements without accelerations. The duration of accelerations was strongly correlated with the duration of movements. The amplitude of accelerations was not clearly correlated with the duration of movements, but depended on the type of movement. The shape of accelerations appeared to be dependent on the timing of the various fetal movements. In 77%, the number of notches in the accelerations was equal to the number of pauses in the movement complications. A discrepancy between notches in accelerations and pauses in movements could be explained in the majority of cases when the timing of the various movements in relation to one another was considered, or by the presence of fetal mouth movements. PMID- 1870061 TI - Continuous intrapartum transcutaneous carbon dioxide measurements during fetal arrhythmia. AB - In nine cases of fetal arrhythmias without cardiac anomalies or congestive heart failure a vaginal delivery was attempted. Due to these arrhythmias adequate fetal heart rate monitoring during labor was not possible. All cases were continuously monitored during labor with the transcutaneous measurement of fetal carbon dioxide tension (tcpCO2). Seven patients could be delivered spontaneously. In one of these cases the newborn was acidotic at birth (pH less than 7.20 in the umbilical artery) which was correctly identified (tcpCO2 greater than 60 mmHg). All newborns were vigorous (Apgar score after 1 minute greater than 7). In cases with uninterpretable fetal heart rate patterns tcpCO2 monitoring of the fetus during labor is an alternative method of fetal surveillance, which identifies fetal distress and can prevent unnecessary operative deliveries. PMID- 1870062 TI - The current status of intrapartum continuous fetal tissue pH measurements. AB - Continuous tissue pH monitoring during labor has now been possible for 15 years. Tissue pH is measured in the intercellular fluid, and the value differs in some cases from the blood pH value because of local capillary flow and local metabolism. The fetal scalp seems to be an area where tissue pH and capillary blood pH values are very close, but in acute acidosis there may be a time lag of 10-15 min before tissue pH is equilibrated. Normal values of scalp tissue pH are 7.38 in early labor declining by 0.016 per hour during the first stage of labor and by 0.12 per hour during the second stage of labor. Tissue pH values below 7.15 are defined as pathological. The correlation coefficient to umbilical artery blood pH (0.71), success rate (67%) and electrode drift (below 0.04) from the largest study of tissue pH monitoring using glass pH electrodes (n = 337) are described. PMID- 1870063 TI - Continuous intrapartum measurement of tissue pH of the human fetus using newly developed techniques. AB - Using a fiberoptic probe with a dye indicator, pH was studied in a group of 124 fetuses. Acidotic tissue pH was found to be a far more powerful indicator of fetal, neonatal and maternal problems than acidotic capillary blood pH. The tissue pH related more consistently to obstetric problems throughout labor. A comparison was made of the reliability of fetal acidotic tissue pH and acidotic capillary blood pH data in the identification and prediction of obstetric problems. PMID- 1870064 TI - Clinical evaluation of guided tissue regeneration in the treatment of maxillary class II molar furcation invasions. AB - This investigation assessed and compared the clinical efficacy of combined open flap debridement/occlusive membrane therapy versus open flap debridement therapy alone, in the treatment of maxillary periodontal furcation defects. Seventeen patients presenting with advanced adult periodontitis, including at least one pair of Class II maxillary furcal defects, comprised the study group. Following completion of a hygienic phase of treatment, measurements were made with calibrated periodontal probes to determine soft tissue recession, probing pocket depths, and attachment levels. Each pair of furcation defects was surgically exposed and hard tissue measurements obtained. Defects were treated with either open flap debridement and a polytetrafluoroethylene periodontal membrane or open flap debridement alone. Membranes were removed at 4 to 6 weeks. Six months postsurgery, soft tissue measurements were repeated and all sites were surgically re-entered to obtain hard tissue measurements. No statistically significant differences were found in recession, probing depth reductions, clinical attachment gains, or resorption of alveolar crest height between test and control groups. Results for these parameters were inconsistent and unpredictable. Statistically significant improvements were found, however, in horizontal open probing attachment (HOPA) and vertical open probing attachment (VOPA) between experimental and control sites. The GTR procedure as used in this study likely has limited application as a therapeutic modality for Class II furcations of maxillary molars. Modifications or improvements in the procedure may result in more predictable healing of these lesions. PMID- 1870065 TI - Treatment of periodontal furcation defects. Mandibular class III defects. AB - Twenty-seven mandibular class III furcation defects were treated in 27 subjects using a regenerative therapy that included citric acid root conditioning and coronally positioned flaps secured by crown-attached sutures. In addition to this therapy, 13 of the 27 defects received freeze-dried, decalcified allogenic bone grafts. The effect of these therapies was evaluated from soft tissue probing measurements, including furcation probings to determine soft tissue closure of the defects. At 6 months postsurgery, the mean vertical probing depth reduction and the mean probing attachment level gain in the furcation area were 2.6 mm and 2.2 mm for the non-grafted defects and 1.9 mm and 1.5 mm for the grafted defects. One of the 14 non-grafted defects and 3 of 13 grafted defects were judged to show soft tissue clinical closure by a panel of 3 independent examiners. No statistically significant differences were observed between defects treated with or without bone grafts. PMID- 1870066 TI - Changes in hemoglobin concentration and oxygen saturation in human gingiva with decreasing inflammation. AB - The purpose of this study was to determine if functional changes in the human gingival vasculature were reversible following the resolution of gingival inflammation. Ten patients with 40 inflamed gingival sites were evaluated before and 2 weeks after the completion of treatment. We determined the hemoglobin concentration and the oxygen saturation of hemoglobin at each site by tissue reflectance spectrophotometry. With the use of treatment including motivation, oral hygiene instruction, and scaling, clinical parameters such as the gingival and plaque indices, the Periotron score, and the probing depth were altered toward a healthier state. With the resolution of gingival inflammation, the increased hemoglobin concentration and decreased oxygen saturation in the inflamed gingiva were restored to normal levels. These findings suggest that reversible changes in the local hemoglobin concentration and oxygen saturation are associated with decreasing gingival inflammation in human subjects. PMID- 1870067 TI - Destructive forms of periodontal disease in adolescents. A 3-year longitudinal study. AB - We studied the periodontal disease progression and the relationship between some forms of destructive periodontitis in a group of Brazilian adolescents with high prevalence of periodontal destruction, and evaluated the adequacy of reducing data by limiting the measurement of disease to first molars and by aggregating and pooling site-scores into subject-level scores. Over a period of 3 years 222 adolescents were examined annually by bite-wing radiographs. Individuals displaying arc-shaped bone lesions adjacent to greater than or equal to 2 first molars were diagnosed as juvenile periodontitis (JP) patients, while those with greater than or equal to 1 first molars showing vertical lesions were regarded as periodontal risk subjects. Teenagers with greater than or equal to 2 first molars exhibiting longitudinal bone loss were defined as high-risk patients. At the ages of 13 and 16 years, 3 (1.3%) and 4 (1.8%) subjects had JP, while 12 (5.4%) and 28 (12.6%) were regarded as periodontal risks; 8 (3.6%) subjects were assigned to the high-risk group; 4 (1.8%) 13-year olds had greater than or equal to 1 first molars missing; hence, no loss of posterior teeth occurred over a period of 3 years. Analyzing the data at the site-level revealed progressive loss and little fluctuation in the alveolar bone height in the high-risk group, and a more pronounced bone loss at the mesial than at the distal surfaces. Simpler data sets were constructed by aggregating some of the site-scores or by pooling these into subject-level scores.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870068 TI - Incidence of periodontitis recurrence in treated patients with and without cultivable Actinobacillus actinomycetemcomitans, Prevotella intermedia, and Porphyromonas gingivalis: a prospective study. AB - A total of 98 adults previously treated for moderate to advanced periodontitis and on a trimonthly recall schedule were screened for the presence of critical levels of Actinobacillus actinomycetemcomitans, Prevotella (Bacteroides) intermedia, and Porphyromonas (Bacteroides) gingivalis. Patients with at least 2 positive sites were placed in a positive group and patients without or with low levels of these bacteria in a negative group. During the 30-month study the incidence of disease recurrence was greater in the positive group, but did not reach statistical significance. Positive patients with deeper pockets tended to be at greater risk of developing recurrent disease than those with shallower pockets. In the positive group only, both A. actinomycetemcomitans recovery and antibody levels to A. actinomycetemcomitans strain NCTC 9710 (serotype c) were inversely correlated with disease recurrence. The presence of A. actinomycetemcomitans and P. intermedia above critical levels did not reliably predict future episodes of disease recurrence in this population. The sparse recovery of P. gingivalis did not permit us to assess its diagnostic value. With the exception of P. gingivalis, for which insufficient data were available, the results indicate that the presence or absence of the above bacterial species cannot of itself serve as a reliable predictor of future episodes of recurrent disease in a population of treated patients on a regular trimonthly recall schedule. PMID- 1870069 TI - Odontogenic myxoma. Report of a periodontally-located case. AB - In this article, a case of odontogenic myxoma with deceptively bland radiographic findings and a clinical impression of periodontal abscess is presented. PMID- 1870070 TI - Plasma cell gingivitis of unusual origin. A case report. AB - Plasma cell gingivitis is a rare benign condition of the gingiva. It is marked by a dense infiltrate of normal plasma cells separated into aggregates by strands of collagen. It is a hypersensitivity reaction to some antigen, often flavorings or spices. The importance of this lesion is that it may cause severe gingival inflammation, discomfort, and bleeding and may mimic more serious conditions. Plaque control and conventional periodontal therapy alone will not cure this disease. The etiologic agent must be identified and the substance eliminated from use. This report outlines a case of plasma cell gingivitis which may have been brought on by the use of red peppers in cooking. PMID- 1870071 TI - Episodic factitious gingival injury secondary to topical anesthesia. A case report. AB - The contribution of topical anesthesia to the incidence of severe factitious gingival injury in an adult patient is reported. A brief review of the literature is also presented. PMID- 1870072 TI - Re: Allergic contact dermatitis and latex gloves. PMID- 1870073 TI - Proceedings of the 21st symposium on drug metabolism and action. October 31 November 2, 1990, Tokushima. PMID- 1870074 TI - Blood viscosity measurement for screening of affecting blood circulation. AB - An in vitro screening test for drugs that decrease blood viscosity was carried out on many pharmacologically active compounds such as Ca-antagonists, alpha antagonists, beta-antagonists, alpha, beta-antagonists, alpha-agonists, beta agonists, alpha, beta-agonists, autacoids and others. The results revealed that various types of microcirculatory-improving drugs, vasodilators, and antagonists decreased blood viscosity, while the agonists and autacoids had no significant effect. These findings suggest that this assay is useful for screening compounds related to hemorheology. PMID- 1870075 TI - Opposite effects of metoclopramide and propantheline on intestinal absorption of imipramine in rats. AB - Intraperitoneally administered metoclopramide (MCP) markedly increased the serum concentration of imipramine (IPM) soon after oral administration. In contrast, intraperitoneally administered propantheline (PPT) slightly decreased the serum concentration. The administration of these two drugs had no significant effect on the serum concentration of IPM after intravenous bolus administration. It was concluded from pharmacokinetic analyses and gastric emptying experiments that the administration of MCP markedly increased the rate of IPM absorption by counteracting the gastric emptying delayed by IPM, but that the administration of PPT slightly decreased the rate of IPM absorption by strengthening the gastric emptying also delayed by IPM. PMID- 1870076 TI - Local drug delivery systems for the treatment of periodontal disease. AB - Filmy local drug delivery systems (LDDSs) were administered to periodontal pockets in beagles with induced periodontitis, and the in vivo-in vitro correlation of drug release from the LDDS and changes in the clindamycin (CLDM) concentration in the periodontal pocket fluid were studied. The in vitro drug release rate from the LDDS was determined by the dissolution study, without agitation, using phosphate buffer as the dissolution medium at 37 degrees C, and the in vivo drug release rate was determined according to the decrease in the drug load remaining in the LDDS after administration in periodontal pockets. The in vivo drug release rate from LDDSs was lower than the in vitro rate determined by the dissolution study, but the two rates showed a correlation in LDDSs that released drugs by diffusion. Therefore, the in vivo drug release rate was considered to be estimated from the results of the in vitro dissolution study. Changes in the drug concentration in the periodontal pocket fluid after administration of LDDS were dependent on the drug release properties of the LDDS. Also, when CLDM was administered as an aqueous solution in periodontal pockets, its concentration in the periodontal pocket fluid decreased according to a pseudo first-order equation. Therefore, the concentration in the periodontal pocket fluid after administration of a LDDS is considered to be simulated by the one compartment model based on a pseudo first-order elimination process. PMID- 1870077 TI - Effect of carrier-mediated transport system on intestinal fosfomycin absorption in situ and in vivo. AB - Intestinal absorption mechanism of fosfomycin (FOM), a water-soluble and small molecular antibiotic, at the clinical dose level was examined by both in situ single-pass perfusion technique of rat small intestine and oral administration in rat in vivo. Analyzing the luminal concentration-dependence of FOM absorption rates in situ by the equation composed of two terms of carrier transport of Michaelis-Menten type and simple-diffusion, apparent Michaelis constant (Kt), maximal transport velocity (Jmax), and first-order diffusive absorption clearance (Kd) were 1.13 mM, 2.54 nmol/min/cm length, and 0.551 microliters/min/cm length, respectively. At the low FOM concentration in the lumen (0.1 mM), its absorption was reduced to about 60% of the control by inorganic phosphate ion at 1.0 mM in the same manner as the uptake in brush border membrane vesicles of rat small intestine (BBMVs) in vitro. Both the glycol form of FOM at 10 mM, the hydrolyzed metabolite of FOM in the stomach juice, and FOM itself at 10 mM reduced FOM absorption by about 50%, indicating the metabolite to be transported by the same carriers as those of FOM. At the higher FOM concentration (5 mM), its absorption was not reduced by any inhibitor described above. No inhibitory effect of 50 mM phosphate ion on FOM absorption following the oral dosing of 20 mg/kg FOM was found. It was concluded that FOM absorption at the clinical dose (10-20 mg/kg) is barely inhibited by the carrier-mediated system via phosphate transport system observed in the in vitro BBMVs. PMID- 1870078 TI - Effects of prolonged treatment with beta-adrenoceptor antagonist, carteolol on systemic and regional hemodynamics in stroke-prone spontaneously hypertensive rats. AB - The present study was designed to determine the regional hemodynamic effects of prolonged beta-adrenergic receptor inhibition in conscious stroke-prone spontaneously hypertensive rats (SHRSP) using a radioactive microsphere method. When the regional blood flow was compared between 10 and 30 weeks of age, the age related changes in organ blood flow were observed in several organs, i.e., the reduction of flow rate in kidney, adrenal gland and intestines. The reduction of flow rate in these organs contributes strongly to the age-related rise of total peripheral resistance. Carteolol, a beta-adrenoceptor antagonist, was given at a dose of 10 mg/kg/d from 10 to 30 weeks of age. These animals gained more weight than the untreated control SHRSPs, and heart rate was reduced significantly. Blood pressure was not affected. However, the prolonged treatment with carteolol prevented the age-related reduction of the blood flow rate in the kidney, adrenal gland and intestines. Thus, our findings indicate that carteolol had appreciable and beneficial effects on the maintenance of flow rates in the above organs of SHRSP without any change in blood pressure. PMID- 1870079 TI - [An olfactory memory of significance for reproductive endocrinology]. PMID- 1870080 TI - Clinical aspects of acute rheumatic fever. AB - We review the epidemiology and clinical features of recent outbreaks of acute rheumatic fever. The history of this disorder as well as current management practices are also discussed. PMID- 1870081 TI - Death in Denmark: a reply. AB - This reply to Martyn Evans's support for a cardiac-centered concept of death attempts to meet some objections to the brainstem definition of death. Evans's appeal to Wittgenstein's philosophy is also criticised. PMID- 1870082 TI - Ethics in preventive medicine. PMID- 1870083 TI - Human embryos and the argument from potential. PMID- 1870084 TI - Ethics and embryos. AB - In this paper we argue that the human form should be seen to exist, in a longitudinal way, throughout the continuum of human growth and development. This entails that the moral value of that form, which we link analytically to the adult, interacting, social and rational being, attaches to all phases of human life to some extent. Having established this we discuss the consequences it has for the moral status of the human embryo. We then apply this argument, and the resulting moral status, to the area of reproductive technology. In doing this we show that there are certain regulations and controls which ought to apply to the use of these infertility treatments. PMID- 1870085 TI - Fetal tissue transplantation: can it be morally insulated from abortion? AB - Ethical controversy over transplantation of human fetal tissue has arisen because the source of tissue is induced abortions. Opposition to such transplants has been based on various arguments, including the following: rightful informed consent cannot be obtained for use of fetal tissue from induced abortions, and fetal tissue transplantation might result in an increase in the number of abortions. These arguments were not accepted by the National Institutes of Health (NIH) Human Fetal Tissue Transplantation Research Panel. The majority opinion of the panel stated that abortion and fetal tissue use are entirely separate issues, and that tissue use is ethically acceptable because it can be morally insulated from the issue of abortion. In support of this view, panel members and others have replied to the arguments put forward by opponents of fetal tissue use. However, replies to the two arguments mentioned above have been unsatisfactory, and the shortcomings of those replies are identified herein. Examination of the arguments pro and con suggests that fetal tissue use cannot be completely insulated from the issue of abortion. Thus, in seeking an ethical justification for fetal tissue transplantation we must consider reasons other than those put forward by the NIH panel. In this paper it is argued that whatever wrong is involved in using fetal tissue from induced abortions must be balanced against the benefits for patients, and it is on this basis that fetal tissue transplantation can be ethically justified. PMID- 1870086 TI - Psychopathic disorder: a category mistake? AB - Although the concept of psychopathy retains its currency in British psychiatry, apparently being meaningful as well as useful to practitioners (1), it is often taken to refer to a purely legal category with social control functions rather than a medical diagnosis with treatment implications. I wish, in this brief article, to suggest that it is essentially, and most usefully, an ethical category which stands outside the diagnostic framework of present-day psychiatry. PMID- 1870087 TI - Psychopathic disorder: a category mistake? A legal response to Colin Holmes. AB - Holmes is concerned with a conflict between law and medicine about the problem of psychopathy, in particular as it relates to homicide. He looks for a consistent set of legal principles based on a variety of medical concepts and in doing so criticises the court for its commonsense approach, its disregard for medical evidence and for employing lay notions of responsibility and illness. This commentary explores how Holmes's notions fit into existing legal rules and explains how the court seeks the assistance of medical evidence when looking at the evidence as a whole to enable it to decide upon issues of defence, which involve legal and not medical concepts. PMID- 1870088 TI - The rules of insanity: commentary on: psychopathic disorder: a category mistake? AB - This paper addresses Colin Holmes's suggestion that the psychopathic disorder is best regarded not as a psychiatric concept, but as an ethical one. The paper argues that the concept of psychopathy, like many other concepts, can span both psychiatry and ethics, and that it is not clear what removing if from the realm of psychiatry would entail. Also, the question of whether the concept of psychopathy is useful for psychiatrists must be separated from the question of whether psychopaths should be exonerated from the moral and legal responsibility for their actions. PMID- 1870089 TI - A nation of people called patients. AB - The implications of the causal and ubiquitous use, by doctors health-workers and politicians, of the word 'patient' are here discussed. Given that the many implications of this noun do not include health or normality (rather the contrary), it is questionable who, if anyone, profits from its indiscriminate use -and its use, even, at all. PMID- 1870090 TI - Literature and medicine. AB - There are various ways in which medicine and literature interact, but this paper concentrates on the contribution which literature can make to 'whole person understanding'. Scientific understanding is concerned with seeing events and actions in terms of patterns or similarities. But 'whole person understanding' is concerned with uniqueness or with what it is for a given person to have an illness. Literature can in various ways develop this kind of understanding. PMID- 1870091 TI - Buying human kidneys: autonomy, commodity and power. AB - Buttle's reply to my objections to buying kidneys is helpful but unconvincing in two respects. Doing something freely leaves quite open the possibility that one is thereby making a commodity of a person; and the effects of institutionalising such a practice is itself a matter for concern. And while his emphasis on 'power' is important, the concept is hardly less problematic than 'commodification'. PMID- 1870093 TI - Localisation of the MRX3 gene for non-specific X linked mental retardation. AB - A family is described with five affected males segregating a new gene for non specific X linked mental retardation (MRX). Linkage analysis localised the gene at Xq28-qter. The maximum lod score was 2.89 with DXS52 (St14) at theta = 0.0. A recombinant was observed with DXS304 (U6.2) defining the proximal limit to the localisation. No evidence for linkage was determined using markers at several points along the remainder of the X chromosome, including the regions known to contain MRX1 and MRX2. This delineates the third gene for non-specific X linked mental retardation, MRX3. PMID- 1870092 TI - X linked mental retardation. PMID- 1870094 TI - Non-specific X linked mental retardation. AB - Non-specific X linked mental retardation (MRX) is mental retardation in persons of normal physical appearance who have no recognisable features apart from a characteristic pedigree. Review of published reports shows that there is clinical variability in the degree of mental retardation within families and genetic heterogeneity, based on gene localisation, between families. We propose a classification based on genetic localisation and a set of minimal clinical features that should be recorded in the hope of identifying possible specific phenotypes. PMID- 1870095 TI - Autosomal dominant inheritance of abnormalities of the hands and feet with short palpebral fissures, variable microcephaly with learning disability, and oesophageal/duodenal atresia. AB - We report two families with an autosomal dominant syndrome of abnormalities of the hands and feet, short palpebral fissures, and variable microcephaly with learning disability. Between a third and a quarter of cases are born with oesophageal atresia, duodenal atresia, or both. Individual patients have hypoplastic thumbs or congenital heart disease. The phenotype of the syndrome reported here is similar to that observed in 13q22-qter deletion patients. However, chromosome analysis has not detected any structural abnormality in our patients. PMID- 1870096 TI - On the incidence of fits and mental retardation in tuberous sclerosis. AB - OBJECTIVES: To establish the frequency of fits and mental retardation in an unbiased group of tuberous sclerosis patients. METHODS: Known tuberous sclerosis families with more than one affected person were ascertained for a genetic linkage study. A number of members were born after genetic counselling had been given after identification of the proband. These subjects were then carefully examined clinically and in many cases with cranial computerised tomography, renal ultrasound, and skeletal survey but not echocardiography. They provide an unbiased group of tuberous sclerosis patients and allow affected patients with normal intellect to be diagnosed. PATIENTS: Thirty-seven tuberous sclerosis families were ascertained and 26 patients born after the family proband were identified. RESULTS: Sixteen of these 26 patients suffered fits (62%) and 10 patients were mentally retarded (38%). CONCLUSIONS: A lower incidence of fits and mental retardation has been found in an unbiased sample of tuberous sclerosis patients. The lifetime risk for fits might be higher had we been able to follow the patients for longer. However, we believe these are more appropriate figures to use in genetic counselling for this disease. PMID- 1870097 TI - The Holt-Oram syndrome. PMID- 1870098 TI - Deletion of chromosome 13 in Moebius syndrome. AB - A girl aged 2 1/2 years with Moebius syndrome was found to have a deletion of band q12.2 in chromosome 13 (46,XX,del(13)(q12.2]. This is the second report concerning involvement of chromosome 13q and Moebius syndrome. The observation raises the possibility that a gene responsible for Moebius syndrome is located in this region of chromosome 13. PMID- 1870099 TI - Non-penetrance in tuberous sclerosis. AB - Non-penetrance has not been reported in tuberous sclerosis when modern non invasive investigations have been performed. We report a four generation family in which there was a subject with minimal expression and another with non penetrance between a great grandfather and his great grandson. This situation highlights the need for full investigation of children of tuberous sclerosis patients before counselling a low recurrence risk for the disease. PMID- 1870100 TI - A fertile male with cystic fibrosis: molecular genetic analysis. AB - A family study is presented in which the father of a girl with severe cystic fibrosis (CF) was also found to have CF but was mildly affected. He was diagnosed with three positive sweat tests including one after suppression with fludrocortisone. Genetic analysis showed that he is a compound heterozygote with the delta F508 CF mutation associated with haplotype B and a second CF mutation associated with haplotype C. In this unusual, fertile CF male, the late age of diagnosis (30 years) and the mild clinical picture suggest that the compound genotype (delta F508/other CF mutation) determines a much less severe form of the disease which might have gone unnoticed in the absence of a severely affected child. The implications of these findings for genetic counselling of families with CF are discussed. PMID- 1870101 TI - Unknown syndrome: proportionate short stature, mandibular prognathism, and short femoral necks. PMID- 1870102 TI - Cranioectodermal dysplasia in sibs. PMID- 1870103 TI - Partial trisomy 13q resulting from a paternal reciprocal Yq;13q translocation. PMID- 1870104 TI - Translocation 19;Y in a child with Bannayan-Zonana phenotype. PMID- 1870105 TI - Genes for intelligence on the X chromosome. PMID- 1870106 TI - X linked complicated spastic paraplegia, MASA syndrome, and X linked hydrocephalus owing to congenital stenosis of the aqueduct of Sylvius: variable expression of the same mutation at Xq28. PMID- 1870107 TI - Ultrastructural aluminium detection in amphibian tissues by electron spectroscopic imaging and electron energy-loss spectroscopy. AB - Aluminium causes a variety of toxic effects in living organisms but very little is known about its uptake, pathways and locations of deposition. We have applied electron spectroscopic imaging (ESI) and electron energy-loss spectroscopy (EELS) to locate aluminium at the ultrastructural level in amphibian larvae from acidic ponds. It is found diffusely bound or precipitated in cell organelles. The spatial resolution of aluminium detection is high. The elemental composition of small areas can be demonstrated by EELS. Three different fixation procedures give similar results. The two- and three-window methods at the K- and L-edges are compared. PMID- 1870108 TI - Progress in electron microscopic diagnostics: semi-quantitative determination of precipitable calcium in different cell types of the organ of Corti in the guinea pig. AB - Potassium antimonate was used to precipitate calcium in the cochlea of the guinea pig. The distribution of the calcium antimonate precipitates was analysed by electron microscopy. The precipitate density was determined in different cell types in the organ of Corti by counting the number of calcium binding sites in a 10-micron 2 area. The size of the precipitates varied considerably, and thus the relative amount of the precipitable calcium was estimated only semi quantitatively. As the prominent carbon signal is superimposed over the nearby small Ca(2+)-edge signals, the combined signal of the antimony M4,5-edge and the oxygen K-edge of the calcium antimonate salt formed was chosen for the semi quantitative estimation. Images of the inelastically scattered electrons of the precipitates at delta E = 570 eV were recorded by electron spectroscopic imaging. The area covered by the calcium precipitates within a given cell type was determined in different ultrathin sections of the same organ of Corti by an image processing system. PMID- 1870109 TI - Demonstration of calcium in dermal melanocytes of Xenopus laevis and Poecilia reticulata with electron energy-loss spectroscopy and electron spectroscopic imaging. AB - The subcellular distribution of calcium in dermal melanocytes of Xenopus laevis and Poecilia reticulata has been analysed. Using two cytochemical methods, phosphate precipitation and a combined oxalate-pyroantimonate technique, electron energy-loss spectroscopy and electron spectroscopic imaging have been applied for elemental analysis. Both precipitation techniques revealed a high calcium content in the melanosomes of both species. Calcium was also located in the vicinity of collagen fibrils and in the plasma membrane. PMID- 1870110 TI - Electron spectroscopic diffraction and imaging of the early and mature stages of calcium phosphate formation in the epiphyseal growth plate. AB - A review of different models of biomineralization in collagen-rich hard tissues shows that further investigations of crystal formation are necessary. The electron spectroscopic diffraction (ESD) mode of operation of an energy-filtering electron microscope offers the possibility of being able to avoid the background from inelastic scattering in selected-area electron diffraction patterns. First experiments on the different stages of mineralization in the epiphyseal growth plate have only indicated the presence of apatite. The ESD mode can be complemented by the electron spectroscopic imaging mode and by elemental mapping of calcium. PMID- 1870111 TI - Quantitative analysis of electron energy-loss spectra from ultrathin-sectioned biological material. I. Optimization of the background-fit with the use of Bio standards. AB - A computer program for quantitative spectral analysis is proposed for the elemental analysis of biological material by electron energy-loss spectroscopy in a conventional transmission electron microscope, the Zeiss EM902. Bio-standards are used to test the performance of this program. The application of a simplex optimization method for curve-fitting is proposed to separate the ionization edge from the background. Making use of Ce-, Ca- and Fe-bio-standards, this method is compared with Egerton's well-known two-area method. PMID- 1870112 TI - Contrast in the electron spectroscopic imaging mode of a TEM. IV. Thick specimens imaged by the most-probable energy loss. AB - When the zero-loss transmission falls below 10(-3) for biological sections of mass-thickness greater than 70 micrograms/cm2, the energy window in the electron spectroscopic imaging (ESI) mode of an energy-filtering electron microscope (EFEM) can be shifted to the most-probable energy loss of the electron energy loss spectrum. This enables mass-thicknesses up to 150 micrograms/cm2 or thicknesses of 1.5 microns to be examined. Electron energy-loss spectra of thick carbon films calculated by a Fourier method agree with experimental spectra. Measurements of the electron energy-loss spectroscopy and ESI image intensities with an additional platinum film confirm a scattering model for the calculation of the image intensity. This model considers the angular broadening at the most probable energy loss by introducing an effective illumination aperture of the order of the full-width at half-maximum of the angular distribution. PMID- 1870113 TI - Quantitative analysis of electron energy-loss spectra from ultrathin-sectioned biological material. II. The application of bio-standards for quantitative analysis. AB - Electron energy-loss spectroscopy (EELS) has been used to determine elemental concentrations in biological specimens, consisting of ultrathin-sectioned cells and tissues. Chelex100-based Ca- and Fe Bio-standards are used for elemental quantification to establish iron and calcium concentrations. These Bio-standards, as well as the biological materials, are treated in a standard EM procedure such that 'known' and 'unknown' sites are located in one cross-section. Uncertainties and variabilities present in the equations for calculating the concentration in the 'unknown' site (determined by comparing simplex-fitted EEL spectra from Bio standards with those from tissue) are outlined in two examples. Using an H+ Bio standard, the matrix composition of such biological cell material is analysed, leading to values which approach each other closely. Quantitative EELS, using Chelex100-based Bio-standards, is advocated. PMID- 1870114 TI - EELS data acquisition, processing and display for the Zeiss CEM 902 based on LOTUS 1-2-3: application examples from a biological system and inorganic transition metal compounds. AB - A personal computer combined with LOTUS 1-2-3 software, including the RS232 module of LOTUS MEASURE and a 12-bit ADC, has been used for data acquisition of electron energy-loss spectroscopy (EELS) spectra with the Zeiss CEM 902. The internal macro language of LOTUS 1-2-3 allows a menu-driven procedure. Macro programs partly combined with external FORTRAN programs can be chosen from the menu for background subtraction, removal of multiple scattering effects by deconvolution, elemental quantification and several utilities. For special applications or conditions the macro programs can easily be modified. Spectra from crystals of two inorganic transition metal compounds, ruthenium trichloride and vanadium disulphide, and from a biological sample are presented as examples of the application of this software. PMID- 1870115 TI - The glycosomes of trypanosomes: number and distribution as revealed by electron spectroscopic imaging and 3-D reconstruction. AB - Computer-aided 3-D reconstruction of trypanosomes from 0.35-micron-thick sections imaged on the Zeiss 902 electron microscope are being used to study the dynamics of cell organization. Segregation of glycolytic enzymes into glycosomes raises questions concerning the distribution and biogenesis of these organelles. Direct counts of glycosomes from Trypanosoma evansi indicate 30-40 per cell and for the closely related T. brucei, 65 per cell. These figures contrast with the estimates of others who have used model-based morphometric methods to obtain a value of 230 per cell. PMID- 1870116 TI - Bone marrow transplantation: a new treatment approach for Mississippians. AB - Bone marrow transplantation makes it possible to treat patients with malignancies using doses of systemic chemotherapy and/or radiotherapy that otherwise would result in fatal hematologic toxicity. This approach has found its widest application in the treatment of hematologic malignancies, but it is also being used for aplastic anemia, severe immunodeficiency diseases, and selected solid tumors. The University of Mississippi will soon (October, 1991) be able to offer this treatment approach to Mississippians; therefore the indications, the general technique, and results of transplantation for a variety of diseases are reviewed herein. PMID- 1870117 TI - Cocaine intoxication in a 12 month-old. PMID- 1870118 TI - Diagnosis and management of amenorrhea. PMID- 1870119 TI - Multiple crystal forms of lipases from Geotrichum candidum. AB - Multiple stable crystal forms of two lipases from the fungus Geotrichum candidum have been obtained. The diffraction pattern extends to beyond 2.0 A resolution. Similarity of the cell dimensions of various forms suggested similar packing of molecules in different crystals. This was confirmed by rotation function results. Four heavy-atoms derivatives have been identified. PMID- 1870120 TI - Crystallization and preliminary X-ray analysis of Gc, the vitamin D-binding protein in serum. AB - The vitamin D-binding protein, Gc, was purified from human serum and crystallized using the hanging-drop method. The best crystals were grown from 28% polyethylene glycol 400 in 50 mM-sodium acetate at pH 4.8. These crystals diffract to 3.4 A and the observed diffraction is consistent with orthorhombic space groups P4(1) and P4(3). The unit cell parameters were determined to be a = b = 135.5 A and c = 75.6 A. PMID- 1870121 TI - Crystals of protein S6 from the 30 S ribosomal subunit of Thermus thermophilus. AB - Crystals of protein S6 from the small ribosomal subunit of an extreme thermophile, Thermus thermophilus, have been obtained by the hanging-drop/vapor diffusion technique using methane pentanediol as a precipitant in the presence of potassium fluoride. The crystals belong to the space group C222 with cell parameters a = 106.7, b = 52.8, c = 41.0 A. They diffract to 2.0 A resolution. PMID- 1870122 TI - Purification and crystallization of recombinant Escherichia coli malate dehydrogenase. AB - Malate dehydrogenase from Escherichia coli has been crystallized with polyethylene glycol and citrate buffer at pH 5.7. The enzyme was obtained from an E. coli strain in which the chromosomal malate dehydrogenase gene was contained on a pBR322 vector. Two types of crystals have been observed; a monoclinic C2 form and an orthorhombic C222(1) form, which is found infrequently. Monoclinic crystals were used as seeds in several rounds of crystallization until large crystals suitable for diffraction analysis were available. A complete X-ray data set to 2.0 A has been collected. PMID- 1870123 TI - Factor-independent activation of Escherichia coli rRNA transcription. I. Kinetic analysis of the roles of the upstream activator region and supercoiling on transcription of the rrnB P1 promoter in vitro. AB - The region from position -154 to position -50 upstream from the start site of transcription of the Escherichia coli rrnB P1 promoter, the upstream activator region (UAR), is required for maximal promoter activity in vivo. Maximal activation (20 to 30-fold) requires the binding of Fis protein in vitro and in vivo. However, two- to fourfold activation remains in vivo even in the absence of Fis. Here, we demonstrate that the presence of the UAR increases the rate of formation of E sigma 70-promoter complexes in vitro in the absence of added protein factors (factor-independent activation). The UAR increases the rate of the RNA polymerase concentration-dependent step in the association pathway to a stable complex formed in the presence of the initiating nucleotides ATP and CTP (RPinit). The rate of dissociation from RPinit is not affected. In addition, a supercoiled template of native superhelical density increases both the association rate for the formation of RPinit and the lifetime of complexes formed in the absence of nucleotides (RPo or open complex), but does not affect factor independent activation. The data are consistent with a model whereby the UAR affects only the initial recognition event (closed complex formation) without affecting either the rate or extent of isomerization to the locally denatured open complex. In the accompanying paper, a variety of chemical and enzymatic probes are used to characterize RPinit and RPo both with and without the UAR. PMID- 1870124 TI - Regulatory elements mediating transcription of the human Ha-ras gene. AB - In order to identify transcriptional regulatory elements controlling the expression of the human Ha-ras gene and to quantitatively assess the role of each element, we made mutations of the transcriptional regulatory region, including 5' and internal deletions, linker scanning and replacement mutations, and combinations of these mutations all fused to the bacterial chloramphenicol acetyltransferase gene. The promoter activity of each of these mutants was determined by measuring the transient expression of chloramphenicol acetyltransferase activity after transfection into human epithelial HeLa cells. We found that the most important regulatory region consists of two closely linked but functionally independent elements, the non-consensus GC-II element, CGGGCGGGC, centered at position -153 from the major transcription start site cluster and a new element, CCGGAA, centered at position -161 directly upstream from GC-II. In addition, there are two functional regulatory elements which make minor contributions to the full promoter activity; a double CCAAT NF-I binding site at position -88 and an unidentified upstream element between positions -199 and -252. Aside from GC-II, the GC boxes, of which there are a total of six between positions -185 and +85, make little or no contribution to Ha-ras promoter activity when individual mutations are tested in growing HeLa cells. The three potential AP2 sites and a weak single NF-I binding site make no contribution. The basal promoter region extending to position -75 from the major start site cluster has no independent activity in this TATA-less gene. PMID- 1870125 TI - Transcriptional organization of the Escherichia coli dnaX gene. AB - We have determined the transcriptional organization of the Escherichia coli dnaX gene, the structural gene for both the gamma and tau subunits of DNA polymerase III holoenzyme. By S1 nuclease protection and primer extension mapping of transcripts encoding the dnaX products, one primary promoter of dnaX has been identified that initiates transcription 37 nucleotides upstream from the first codon. dnaX resides in an operon with two recently sequenced genes, orf12, encoding an unidentified product, and recR, the structural gene for a protein involved in the recF pathway of recombination. Under conditions of balanced growth, a very small amount of transcription from the upstream apt promoter (less than 5%) contributes to the expression of tau and gamma, too low for apt to be considered to be on an operon with dnaX, orf12, and recR are transcribed from an independent promoter as well as from the dnaX promoter, providing a mechanism for orf12 and recR to be regulated independent of dnaX. Transcription of the dnaX orf12-recR operon is terminated upstream from the previously characterized heat shock gene htpG. The dnaX and orf12-recR promoters, cloned into a promoter detection vector, efficiently direct the expression of the downstream reporter gene, lacZ. These results extend our knowledge of the genetic and transcriptional organization of this region of the E. coli chromosome. The transcriptional organization has been defined as follows: apt, dnaX-orf12-recR, htpG. All of these genes are transcribed in the clockwise direction and only dnaX, orf12 and recR are contained in the dnaX operon. PMID- 1870126 TI - Identifying potential tRNA genes in genomic DNA sequences. AB - We have developed an algorithm that automatically and reproducibly identifies potential tRNA genes in genomic DNA sequences, and we present a general strategy for testing the sensitivity of such algorithms. This algorithm is useful for the flagging and characterization of long genomic sequences that have not been experimentally analyzed for identification of functional regions, and for the scanning of nucleotide sequence databases for errors in the sequences and the functional assignments associated with them. In an exhaustive scan of the GenBank database, 97.5% of the 744 known tRNA genes were correctly identified (true positives), and 42 previously unidentified sequences were predicted to be tRNAs. A detailed analysis of these latter predictions reveals that 16 of the 42 are very similar to known tRNA genes, and we predict that they do, in fact, code for tRNA, yielding a false-positive rate for the algorithm of 0.003%. The new algorithm and testing strategy are a considerable improvement over any previously described strategies for recognizing tRNA genes, and they allow detections of genes (including introns) embedded in long genomic sequences. PMID- 1870127 TI - Three-dimensional structure of the complexes between bovine chymotrypsinogen A and two recombinant variants of human pancreatic secretory trypsin inhibitor (Kazal-type). AB - Variants of the human pancreatic secretory trypsin inhibitor (PSTI) have been created during a protein design project to generate a high-affinity inhibitor with respect to some serine proteases other than trypsin. Two modified versions of human PSTI with high affinity for chymotrypsin were crystallized as a complex with chymotrypsinogen. Both crystallize isomorphously in space group P4(1)2(1)2 with lattice constants a = 84.4 A, c = 86.7 A and diffract to 2.3 A resolution. The structure was solved by molecular replacement. The final R-value after refinement with 8.0 to 2.3 A resolution data was 19.5% for both complexes after inclusion of about 50 bound water molecules. The overall three-dimensional structure of PSTI is similar to the structure of porcine PSTI in the trypsinogen complex (1TGS). Small differences in the relative orientation of the binding loop and the core of the inhibitors indicate flexible adaptation to the proteases. The chymotrypsinogen part of the complex is similar to chymotrypsin. After refolding induced by binding of the inhibitor the root-mean-square difference of the active site residues A186 to A195 and A217 to A222 compared to chymotrypsin was 0.26 A. PMID- 1870128 TI - Structures of met and azidomet hemerythrin at 1.66 A resolution. AB - The crystallographic refinement of met and azidomet hemerythrin has been carried out at 1.66 A resolution in an attempt to characterize precisely the binuclear iron center in this protein. Restrained least-squares refinement has produced molecular models giving R-values of 18.9% for met (65,683 reflections from 10 A to 1.66 A) and 17.6% for azidomet hemerythrin (68,747 reflections from 10.0 A to 1.66 A). The protein structure in each derivative is very similar to that of myohemerythrin. The mu-oxo bridged iron center differs between the two forms. The complex in met hemerythrin is asymmetric with the bridging oxygen closer to one of the iron atoms while the complex in azidomet hemerythrin is symmetric. After investigations of the effects of correlation in the refinement, we believe this difference between the two complexes is associated with chemical differences and is not a refinement artefact. PMID- 1870129 TI - Refined X-ray crystal structures of the reactive site modified ovomucoid inhibitor third domains from silver pheasant (OMSVP3*) and from Japanese quail (OMJPQ3*). AB - Tetragonal and triclinic crystals of two ovomucoid inhibitor third domains from silver pheasant and Japanese quail, modified at their reactive site bonds Met18 Glu19 (OMSVP3*) and Lys18-Asp19 (OMJPQ3*), respectively, were obtained. Their molecular and crystal structures were solved using X-ray data to 2.5 A and 1.55 A by means of Patterson search methods using truncated models of the intact (virgin) inhibitors as search models. Both structures were crystallographically refined to R-values of 0.185 and 0.192, respectively, applying an energy restraint reciprocal space refinement procedure. Both modified inhibitors show large deviations from the intact derivatives only in the proteinase binding loops (Pro14 to Arg21) and in the amino-terminal segments (Leu1 to Val6). In the modified inhibitors the residues immediately adjacent to the cleavage site (in particular P2, P1, P1') are mobile and able to adapt to varying crystal environments. The charged end-groups, i.e. Met18 COO- and Glu19 NH3+ in OMSVP3*, and Lys18 COO- and Asp19 NH3+ in OMJPQ3*, do not form ion pairs with one another. The hydrogen bond connecting the side-chains of Thr17 and Glu19 (i.e. residues on either side of the scissile peptide bond) in OMSVP3 is broken in the modified form, and the hydrogen-bond interactions observed in the intact molecules between the Asn33 side-chain and the carbonyl groups of loop residues P2 and P1' are absent or weak in the modified inhibitors. The reactive site cleavage, however, has little effect on specific interactions within the protein scaffold such as the side-chain hydrogen bond between Asp27 and Tyr31 or the side-chain stacking of Tyr20 and Pro22. The conformational differences in the amino-terminal segment Leu1 to Val6 are explained by their ability to move freely, either to associate with segments of symmetry-related molecules under formation of a four-stranded beta-barrel (OMSVP3* and OMJPQ3) or to bind to surrounding molecules. Together with the results given in the accompanying paper, these findings probably explain why Khyd of small protein inhibitors of serine proteinases is generally found to be so small. PMID- 1870130 TI - Kinetic analysis of the acid and the alkaline unfolded states of staphylococcal nuclease. AB - Thermodynamic analysis by differential scanning calorimetry shows that the folding/unfolding transition of staphylococcal nuclease is consistent with the two-state process. Stopped-flow kinetic measurements, monitoring the Trp140 fluorescence and covering five decades in time (2 ms to 300 s), indicate that the unfolding from pH 7.0 to 3.1 is monophasic (time constant 1.15 s) and from pH 7.0 to 12.2 is biphasic (time constants: one less than 2 ms and the other 0.6 s). However, the folding, either from pH 3.1 to 7.0 or from pH 12.2 to 7.0, is triphasic (time constants 150 ms, 850 ms and 30 s from acid, 90 ms, 565 ms and 33 s from alkaline). A simple sequential model, which agrees with the above observations for acidic folding/unfolding is, D3 in equilibrium D2 in equilibrium D1 in equilibrium N. The three Ds denote three sub-states of the unfolded state and N denotes the native state. These sub-states of D have similar enthalpy and tryptophan fluorescence, and their equilibrium cannot be shifted by temperature changes. However, they are kinetically distinctive. Data do not favor alternative mechanisms assuming parallel transitions of the three Ds to N, or complexity of the N state, or parallel transitions of sub-states of N1, N2 and N3 to D. Other more complex, branched or cyclic, kinetics are not considered because of the lack of evidence, pH dependence of the unfolding kinetics suggests that the unfolding is triggered by protonation of 0.8(+/- 0.3) ionizable groups, with a pKa of 3.9 or by deprotonation of 1.6(+/- 0.4) ionizable groups with pKa values near 10.5. Circular dichroisms indicate that these three D states retain nonrandom chain conformation. Possible role of these "chain conformation" in the protein folding is discussed. PMID- 1870131 TI - Surface electrostatic interactions contribute little of stability of barnase. AB - Electrostatic interactions are believed to play an important role in stabilizing the native structure of proteins. We have quantified the contribution to stability of an interaction between two oppositely charged side-chains on the surface of barnase. Using site-directed mutagenesis, glutamate 28 and lysine 32 were introduced onto the solvent-accessible side of the second alpha-helix in barnase. These two residues are separated by one turn of the helix, and so are ideally situated for their opposite charges to interact. Double mutant cycle analysis reveals that the interaction between Glu28 and Lys32 contributes only approximately 0.2 kcal/mol to stability of the protein. All other interactions between exposed charged side-chains in barnase examined so far also contribute little to stability. We explain this low value by their location on the surface, rather than in the interior, of the protein. PMID- 1870133 TI - Program and abstracts of the 8th G.R.R.C. meeting. Paris, France, 4-5 April 1991. PMID- 1870132 TI - Heterotropic interactions in Escherichia coli aspartate transcarbamylase. Subunit interfaces involved in CTP inhibition and ATP activation. AB - In Escherichia coli aspartate transcarbamylase, each regulatory chain is involved in two kinds of interfaces with the catalytic chains, one with the neighbour catalytic chain which belongs to the same half of the molecule (R1-C1 type of interaction), the other one with a catalytic chain belonging to the other half of the molecule (R1-C4 type of interaction). In the present work, site-directed mutagenesis was used to investigate the involvement of the C-terminal region of the regulatory chain in the process of feed-back inhibition by CTP. Removal of the two last C-terminal residues of the regulatory chains is sufficient to abolish entirely the sensitivity of the enzyme to CTP. Thus, it appears that the contact between this region and the 240s loop of the catalytic chain (R1-C4 type of interaction) is essential for the transmission of the regulatory signal which results from CTP binding to the regulatory site. None of the modifications made in the R1-C4 interface altered the sensitivity of the enzyme to the activator ATP, suggesting that the effect of this nucleotide rather involves the R1-C1 type of interface. These results are in agreement with the previously proposed interpretation that CTP and ATP do not simply act in inverse ways on the same equilibrium. PMID- 1870134 TI - The effects of 4-aminopyridine on neurological deficits in chronic cases of traumatic spinal cord injury in dogs: a phase I clinical trial. AB - A Phase I trial of 4-aminopyridine (4-AP) was carried out in 39 dogs referred to the veterinary teaching hospital with naturally occurring traumatic paraplegia or paraparesis. The rationale for the study was provided by the observation that 4 AP restores conduction in demyelinated nerve fibers in experimental spinal cord injury. Most injuries (77%) resulted from degenerative disk disease, occurring at or near the thoracolumbar junction, and producing chronic, complete paraplegia. Neurological examination of each dog was recorded on videotape before and at intervals after administration of 4-AP. The drug was administered systemically in total doses between 0.5 and 1 mg/kg body weight. Three areas of neurological status changed significantly at 15-45 minutes following administration of 4-AP: (a) striking improvements in hindlimb placing occurred in 18 animals; (b) increased awareness of painful stimuli to the hindlimb in 10 animals; (c) partial recovery of the cutaneus trunci muscle reflex of the back skin in 9 animals. These effects reversed within a few hours of administration. Other animals (36%) showed no change in neurological signs except a slight enhancement of hindlimb reflex tone. Significant side effects were seen in 6 dogs receiving higher intravenous doses, with elevation of body temperature and apparent anxiety, leading to mild seizures in 3 of the animals. These seizures were controlled with diazepam. The results indicate that conduction block may contribute significantly to functional deficits in closed-cord injuries and that potassium channel blockade may prove to be a valid, if limited approach to therapeutic intervention in chronic paraplegia and paraparesis. PMID- 1870135 TI - Evidence for a neural source of acute accumulation of serotonin in platelets in the injured spinal cord of rats. An experimental study using 5,6 dihydroxytryptamine treatment. AB - It was found previously that large numbers of platelets showing high serotonin (5 hydroxytryptamine; 5-HT) immunoreactivity appeared in hemostatic plugs at the traumatized cord segment in the acute phase of a trauma. In order to determine the origin of 5-HT in the platelets, we investigated the 5-HT immunoreactivity of platelets accumulating in hemostatic plugs at the traumatized spinal cord segment at 5 minutes after injury. This investigation was carried out by light and electron microscopic immunohistochemistry in rat spinal cord pretreated with 5,6 dihydroxytryptamine (5,6-DHT). The hemorrhagic lesion formed at the neural 5-HT depleted spinal cord segment was completely 5-HT immunonegative, while platelets in lesions in cord segments of control animals or rostral to the injection site of 5,6-DHT in experimental animals where neural 5-HT was not depleted were 5-HT immunoreactive. The results strongly suggest that a significant amount of 5-HT is released from neural elements at the injury site and is transiently incorporated into the platelets in situ. PMID- 1870136 TI - Cerebrovascular changes in a rat model of moderate closed-head injury. AB - We have developed and tested a rat (Wistar) model of moderate concussion. Concussion is produced by controlled and repeatable mechanical fixed, closed-head injury. Moderate concussion in this model is characterized by 4 to 10 minutes of unconsciousness, absence of skull fractures or brain contusions, and few, if any, acute neurologic symptoms. By 2 hours postinjury, the subsequent trauma is further characterized by regional and global increases in cerebrovascular permeability and decreases in cerebral blood flow. Such changes are accompanied by brain swelling and two phases of elevated intracranial pressure; one lasting about 5 hours with a peak of about 10 mmHg, the other lasting more than 3 days postinjury with a peak of about 30 mmHg. Regional neurohistologic damage detected between 3 and 4 days postinjury correlates for the most part with earlier changes in regional permeability and blood flow. Significant morphologic changes which are characterized by patchy neuronal degeneration can be found in numerous forebrain locations, particularly in the frontal (coup) and entorhinal (contre coup) cortices. These observations have important parallels in human head trauma and suggest that this reliable physiological model may be a useful, relatively simple and inexpensive tool for investigating the mechanisms and therapeutics of head trauma. PMID- 1870137 TI - The fan-wise split preparation method for quantitation of peripheral nerve injuries. AB - The applicability of the fan-wise split preparation method to the analysis of peripheral nerve injuries was explored in an experimental compression injury of the mouse sciatic nerve. The preservation of myelin sheaths was sufficient to enumerate the damaged myelinated fibers. Because of the simplicity and relative ease of the technique, this method could be a useful adjunct for the assessment of therapeutic modalities using experimental animals. PMID- 1870138 TI - Naloxone and experimental spinal cord injury: effect of varying dose and intensity of injury. AB - We have reported previously that high-dose (10 mg/kg) and megadose naloxone (as high as 150 mg/kg) failed to promote recovery of motor function after spinal cord injury in rat. In view of these negative results, in comparison to some reports of benefit of naloxone in the literature, the present study was undertaken to assess lower doses, using a modified 3 x 4 factorial design, to evaluate a range of lower doses in relation to various intensities of cord injury. Sprague-Dawley rats were assigned randomly to 10 groups (n = 10) relating to two factors: intensity of injury and dosage of naloxone. A dynamic-load injury was induced with a 10-g weight dropped from a height of 2.5 cm, 5.0 cm, or 17.5 cm. Animals were treated with naloxone 1 mg/kg, 4 mg/kg, 10 mg/kg, or saline (control). Tests of motor recovery were carried out weekly for 4 weeks postinjury. Histopathological morphometric analysis of the spinal cords was carried out for measurement of residual gray and white matter at the epicenter of the cord injury. In general, the behavioral data showed no improvement in recovery of function, with the possible exception of naloxone at a dosage of 4 mg/kg (not statistically significant at 4 weeks). Independent of naloxone treatment, there was a significant difference among the three intensities of injury. Pathologically, a difference could not be demonstrated in relation to dosage of naloxone, but as in the case of the behavioral data, a graded response occurred as a function of intensity of injury. PMID- 1870139 TI - Three-dimensional computer-assisted analysis of graded contusion lesions in the spinal cord of the rat. AB - Histological analysis of spinal cord injury in experimental animals has focused primarily on the microanatomy of damaged tissue. The current study presents an analysis of the three-dimensional structure of lesion sites in the spinal cord of rats contused with an injury device which produces consistent lesions. Three levels of injury were produced by systematically varying the cord displacement and the duration of the displacement during impact. The resulting groups of subjects exhibited mild, moderate, and severe neurological deficits. Comparisons of equivalent mild impacts made at thoracic versus lumbar spinal cord levels were also made. The results indicate that the overall shape of the lesions is generally biconical, with extensions in the base of the dorsal funiculus, irrespective of the degree of damage or the spinal level of the injury. Lower displacement injuries yielded shorter lesions rostrocaudally with less spread into the white matter. Similar impacts in the lumbar versus thoracic spinal cord produced shorter, more truncated lesion sites at lumbar levels with less involvement of the white matter than in the thoracic lesions. Three-dimensional analyses can can provide additional information about the lesion beyond that available from conventional histopathological measures. Such information could be useful in assessing the results of posttraumatic manipulations which are directed at reducing tissue damage or tissue replacement via transplantation. PMID- 1870140 TI - Carcinogenicity of dioxins. PMID- 1870141 TI - Early detection for prostate cancer? PMID- 1870142 TI - 1971-1991: consumerism grew as cancer became a curable disease. PMID- 1870143 TI - Too many breast biopsies? Watching vs. cutting. PMID- 1870144 TI - Differentiation therapy forces cancer cells to mature. PMID- 1870145 TI - Breast cancer prevention: hold the hormones, please. PMID- 1870146 TI - Congress will face host of NIH issues after recess. PMID- 1870147 TI - Photodynamic killing of human squamous cell carcinoma cells using a monoclonal antibody-photosensitizer conjugate. AB - We have developed procedures in which the photosensitizer benzoporphyrin derivative monoacid ring A (BPD) can be covalently linked to carrier molecules of modified polyvinyl alcohol (PVA) to produce water-soluble PVA-BPD conjugates with a molecular mass in the range of 30 kd. These carriers can subsequently be covalently linked to monoclonal antibodies (MoAbs) using heterobifunctional linking agents. We describe here such a conjugate in which the MoAb (5E8) has specificity for a glycoprotein detected on human squamous cell carcinomas of the lung. We provide evidence that the conjugates produced were covalently linked and retained both their photosensitizing and antigen-binding activities. We show further that the MoAb-PVA-BPD conjugate, in the presence of 10% fetal calf serum, exhibited highly enhanced phototoxic killing of the target cell line (A549) over that exhibited by free BPD or a control MoAb-PVA-BPD conjugate. These results demonstrate, therefore, both the selectivity and specificity of this MoAb conjugate. PMID- 1870148 TI - Case-control study of canine malignant lymphoma: positive association with dog owner's use of 2,4-dichlorophenoxyacetic acid herbicides. AB - A hospital-based case-control study of companion dogs examined the risk of developing canine malignant lymphoma associated with the use of chemicals in and about the home. Information from a self-administered owner questionnaire and/or a telephone interview of about 491 cases, 466 nontumor controls, and 479 tumor controls indicated that owners in households with dogs that developed malignant lymphoma applied 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides to their lawn and/or employed commercial lawn care companies to treat their yard significantly more frequently than control owners (odds ratio = 1.3). In addition, the risk of canine malignant lymphoma rose to a twofold excess with four or more yearly owner applications of 2,4-D. The findings in this study are consistent with occupational studies in humans, which have reported modest associations between agricultural exposure to 2,4-D and increased risk of non-Hodgkin's lymphoma, the histology and epidemiology of which are similar to those of canine malignant lymphoma. The present study suggests that human health implications of 2,4-D exposure in the home environment should receive further investigation. PMID- 1870149 TI - Low-grade, latent prostate cancer volume: predictor of clinical cancer incidence? AB - We hypothesize that each cell in low-grade (Gleason grade 1-3) prostate cancer tissue is at risk of transformation into a cell which produces a high-grade (Gleason grade 4-5) clinical cancer after a short period of growth. As a consequence, the volume of low-grade, latent cancer tissue in the prostate glands of men at any age determines their incidence rate for high-grade, clinical cancer a few years later. Autopsy and incidence data for both white men and black men support this conclusion, with a tumor growth period of about 7 years. The transformation rate is similar for black men and for white men, about 0.024 high grade cancers per year per cm3 of low-grade, latent cancer volume. Our hypothesis explains the infrequent occurrence of clinical cancer despite the high prevalence of latent cancer, the steep rise of clinical cancer incidence with age despite the slow rise of latent cancer prevalence with age, and the disparities in clinical cancer incidence among some populations despite their similar latent cancer prevalence. This hypothesis suggests that low-grade cancer volume is a critical determinant of clinical cancer risk. PMID- 1870150 TI - Effect of cell wall skeleton and monophosphoryl lipid A adjuvant on the immunogenicity of a murine B16 melanoma vaccine. AB - We examined the effect of a new adjuvant consisting of purified mycobacterial cell wall skeleton (CWS) and monophosphoryl lipid A (MPL) on the immunogenicity of a murine melanoma vaccine. C57BL/6 mice were immunized to partially purified B16 melanoma vaccine given alone or together with different dose levels of adjuvant, or with saline or adjuvant alone. Humoral response, delayed-type hypersensitivity (DTH), in vitro cytotoxicity, and tumor-protective immunity to melanoma were measured following three biweekly immunizations. The adjuvant potentiated the antibody response to some, but not all, melanoma antigens in a dose-dependent fashion. The adjuvant also potentiated cellular immunity as measured by in vitro cytotoxicity assays. No potentiation of tumor-protective immunity was detected. In comparison to Freund's complete adjuvant, cell wall skeleton plus monophosphoryl lipid A (CWS:MPL) induced fewer cutaneous toxic effects and stronger antibody and DTH responses but resulted in no greater in vitro cytotoxicity or tumor-protective immunity. Thus, the adjuvant had a selective and dose-dependent effect on humoral responses to vaccine immunization but did not potentiate a tumor-protective immunity to B16 melanoma. PMID- 1870151 TI - Induction of delayed hypersensitivity to human tumor cells with a human monoclonal anti-idiotypic antibody. AB - There is considerable interest in the development of anti-idiotypic antibodies as vaccines in a number of diseases, including cancer. We have developed a human anti-idiotypic monoclonal antibody (105AD7) which binds at or very near to the binding site of mouse antitumor monoclonal antibody 791T/36. The 791T/36 antibody binds to a tumor-associated antigen (gp72) expressed on a number of human tumors, including colorectal and ovarian carcinomas and osteogenic sarcoma. This study shows that, in rats and mice, 105AD7 induces delayed-type hypersensitivity to human tumor cells bearing the gp72 antigen. Local transfer of delayed hypersensitivity was also demonstrated using lymphocytes from mice primed with 105AD7. These findings show that the human monoclonal anti-idiotypic antibody 105AD7 is likely to induce cellular immune responses to tumors in cancer patients. PMID- 1870152 TI - Phase II study of intravenous bolus recombinant interleukin-2 in advanced malignant melanoma: Southwest Oncology Group study. PMID- 1870153 TI - Cancer incidence in Seattle Women's Health Trial Participants by group and time since randomization. PMID- 1870154 TI - Evaluating the differential effect of diet on rat carcinogenesis. PMID- 1870155 TI - Fetal rat septal cells adhere to and extend processes on basement membrane, laminin, and a synthetic peptide from the laminin A chain sequence. AB - Responses of rat embryonic septal cells to reconstituted basement membrane, laminin, and laminin A chain-derived synthetic peptides were studied in culture. Dissociated fetal E16/17 septal cells were grown for three days on differently coated plastic substrata. Reconstituted basement membrane (Matrigel), laminin, and a 19-amino acid synthetic peptide CSRARKQAASIKVAVSADR-NH2 (PA22-2) from the laminin A chain sequence mediated cell-substratum adhesion and promoted neurite outgrowth. In contrast, cells did not attach to or form processes on uncoated plastic or on plastic substrata coated with synthetic, laminin-derived control peptides. Polyethylenimine (PEI) supported the adhesion and survival of fetal septal cells; however, when laminin was added to the medium during cell plating or 18 hr afterward, a dose-dependent increase was observed in neurite outgrowth of cells attached to this substratum. Cells grown for 6 days on PEI in the presence of laminin showed a determined increase in the number of cholinergic neurons as marked by acetylcholinesterase staining. These data suggest that the subpopulation of cholinergic septal neurons present in the septal cells studied here were also responding to laminin. The results of this in vitro study suggest potential uses for basement membrane, laminin, or synthetic peptides, such as PA22-2, in fetal septal grafts to enhance regeneration in the damaged septo hippocampal system. PMID- 1870156 TI - Cytochrome P-45011 beta in rat brain. AB - The presence of cytochrome P-45011 beta in rat brain was studied by immunohistochemistry using polyclonal rabbit antibodies raised against purified bovine adrenocortical P-45011 beta, which is involved in the steroid 11 beta hydroxylation and glucocorticoid formation. The results showed that cytochrome P 45011 beta immunoreactivity is selectively localized to the tracts of myelinated fibers throughout the brain. The specificity of immunohistochemical stainings with P-45011 beta antibodies was established by control tests including nonimmune rabbit immunoglobulin Gs and P-45011 beta antibodies absorbed with purified antigen. Western immunoblots of homogenates from different brain areas with P 45011 beta antibodies, together with biochemical enzymatic assays for cytochrome P-45011 beta monooxygenase activity in these homogenates, confirmed the selective localization of this enzyme observed with immunohistochemistry. Cytochrome P 45011 beta and 11 beta-hydroxylase activity were detected in a homogenate from the cortical white matter (brain area rich in myelinated fibers) as in that from the rat adrenal, but were not detectable in a homogenate from the cerebral cortex (brain area poor in myelinated fibers). Furthermore, quantitation of the P-45011 beta bands on the immunoblots by the areal density revealed that the cortical white matter contains approximately 1.4 pmol of cytochrome P-45011 beta/mg of tissue protein, the value of which was about one sixth of the corresponding value estimated in the rat adrenal. This relatively high content of cytochrome P-45011 beta was also reflected in a relatively high level of 11 beta-hydroxylase activity measured in a homogenate of this brain area by biochemical enzymatic assays using [4-14C]-11-deoxycorticosterone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870157 TI - Characteristics of excitatory amino acid uptake in cultures from neurons and glia from the retina. AB - 3H-D-Aspartate uptake was biochemically characterized in cultures from chick retina enriched in glial (Muller) cells or neurons during progressive days in vitro (DIV). In the neuronal cultures a high-affinity, Na(+)-dependent system was found with Km = 8-13 microM and pharmacological characteristics in agreement with those of reuptake systems in other regions of the CNS. The uptake system in glial cells showed a lower affinity, with Km = 100-135 microM. In both cases, uptake was temperature and energy dependent. A sharp increase in the Vmax of uptake was observed in both neuronal and glial cultures at 5 DIV, at which time morphologically mature synapses have been shown to be present in retinal cultures. A parallel increase in the pharmacological specificity of the uptake system in neuronal cultures was observed, with a rise in the efficiency of D-Asp, L-Asp, L-Glu, and DL-asp- beta-hydroxamate for inhibiting 3H-D-Aspartate uptake. Results suggest the possibility of reuptake participating in the regulation of extracellular glutamate concentration during development. PMID- 1870158 TI - O-2A glial progenitors from mature brain respond to CNS neuronal cell line derived growth factors. AB - During development, myelin-forming oligodendrocytes and type 2 astrocytes are believed to arise from bipotential (O-2A) glial progenitors. Previously we found that conditioned medium (CM) from the B104 rat CNS neuronal cell line promotes growth of neonatal rat O-2A progenitors in serum-free culture conditions with subsequent increases in differentiated progeny. We now report that O-2A progenitors are present in mature rat brains and that this CM promotes the growth, motility, and bipolar morphology of these cells from 30- and 65-day-old rat brains, as shown by quantitative studies using double immunostaining and [3H]thymidine-autoradiography. In addition, the growth-promoting action of B104 CM is not neutralized by antibodies to platelet-derived growth factor, a proposed progenitor mitogen. Subsequent to the proliferation of these O-2A progenitors, increases in oligodendrocytes and type 2 astrocytes occur. These data suggest a novel therapeutic strategy for some demyelinating diseases, e.g., multiple sclerosis, where there is a deficit in oligodendrocytes. Although it has been proposed by others that mature brain O-2A progenitors are less proliferative and thereby incapable of adequately replenishing lost oligodendrocytes in these diseases, we present in vitro evidence for continued response of mature brain O 2A progenitors to this neuronal cell line-derived mitogen. PMID- 1870159 TI - Alpha isoform of smooth muscle actin is expressed in astrocytes in vitro and in vivo. AB - We have previously reported that astroglial cell lines derived from spontaneously immortalized mouse cerebellar cultures as well as primary astrocyte cultures express the mRNA of the alpha isoform of smooth muscle actin. In this report, we have used an antiserum specific for the alpha smooth muscle actin protein to investigate the presence and the pattern of expression of alpha smooth muscle actin protein at the cellular level with immunocytochemical methods. The results show that an anti-smooth muscle vessels alpha actin antiserum labels a typical actin network in the D19 astroglial cell clone and in flat astrocytes of primary cultures derived from various CNS regions of embryonic and postnatal mice. Furthermore, this antiserum labels distinct populations of astrocytes in the adult mouse brain, in particular in the corpus callosum and the fornix. However, in the corpus callosum, astrocytic processes are strongly labeled by anti-SMV alpha actin antibodies only in parasagittal planes. Thus, alpha smooth muscle actin represents a new marker for subsets of astrocytes. PMID- 1870160 TI - Myelin/oligodendrocyte-specific protein: a novel surface membrane protein that associates with microtubules. AB - Only a few proteins are known to be exclusively expressed in central nervous system (CNS) myelin. A novel surface membrane protein expressed only in CNS myelin and oligodendrocytes of higher vertebrates has been identified by a monoclonal antibody. This CNS myelin/oligodendrocyte-specific protein, MOSP, has a molecular weight of 48 kDa and a pI of approximately 6.7. In the presence of the monoclonal antibody, MOSP remains on the surface of cultured oligodendrocytes but becomes associated with cytoplasmic microtubules. Our results suggest that MOSP plays an important role in membrane/cytoskeleton interactions during the formation and maintenance of CNS myelin. MOSP also may play a critical role in the pathogenesis of diseases of CNS myelin. PMID- 1870161 TI - Should otolaryngology be on the endangered species list? PMID- 1870162 TI - Pressure, flow and resistance characteristics of the pediatric Storz-Hopkins bronchoscopes. AB - Poiseuille's law describes the relationship between pressure and the flow of a gas or liquid of known viscosity through a conduit of known length and radius. In clinical bronchoscopy, resistance varies directly with changes in viscosity of the inspired gas and the length of the bronchoscope. According to Poiseuille's law, resistance varies inversely to the fourth power of the radius of the bronchoscope. Flow-pressure curves were generated for commonly used pediatric Storz-Hopkins bronchoscopes with and without telescopes and the resistance of each system was calculated. Extremely high resistance is encountered with the 2.5 x 20 cm bronchoscope with telescope in place, a fact that most pediatric endoscopists are well aware of. However, comparable resistance is encountered when the 3.5 x 30 cm bronchoscope is used with the telescope in place, a fact not well appreciated by most clinicians. PMID- 1870163 TI - Dose-dependent inner ear changes after i.v. administration of cisplatin. AB - The effect on the cochlear and vestibular surface structures in the inner ear of guinea pigs receiving different doses of cisplatin was studied in three groups of animals. A semi-quantitative analysis showed that cisplatin induced outer hair cell (OHC) damage which developed over days, was dose-dependent and that repeated intraperitoneal injections of a low dose of cisplatin caused OHC changes comparable to a single intravenous injection. The range of OHC damage varied generally between the three rows of OHCs, but in the most severely damaged cochleas the changes were equally distributed between the rows in the basal turn. The inner hair cells (IHCs) and sensory cells of the vestibular end organ were unaffected up to five days after an intravenous injection of cisplatin. PMID- 1870164 TI - Polyp of the external ear canal arising from the temporomandibular joint: a case report. AB - A polypoid mass of granulation tissue in the external auditory meatus was found to be arising from the ipsilateral temporomandibular joint (TMJ). The origin of the lesion was suspected clinically and was confirmed by a CT scan study. As the patient showed signs of psoriatic arthritis, it seems likely that this was the underlying pathological process in the joint. A patent foramen of Huschke allowed herniation of synovial tissue from the joint into the external auditory canal. PMID- 1870165 TI - Translabyrinthine identification of the cochlear aqueduct: a helpful landmark during inferomedial temporal bone dissection. AB - Translabyrinthine identification of the cochlear aqueduct (CA) in 20 cadaveric temporal bones allowed anatomical measurements to be made between its horizontal portion and other inferomedial structures. Its role as a landmark during temporal bone surgery is discussed. PMID- 1870166 TI - The effect of glycerol on short-term experimental endolymphatic hydrops. AB - The aim of this paper was to evaluate the effect of one month of treatment with different dosages of glycerol on experimental endolymphatic hydrops produced by obliteration of endolymphatic sac and duct through an extradural approach. Forty two guinea pigs were used. The animals, divided into six groups, received 0.5-2 gr/kg body weight of the drug per day for one month. The activity of glycerol was determined by statistical analysis of volumetric changes of scala media. Glycerol demonstrated the effect of reducing endolymphatic hydrops. The decrease in hydrops was influenced by the dosage suggesting a stria metabolic response. PMID- 1870167 TI - The safety and efficacy of Emla cream topical anesthesia for myringotomy and ventilation tube insertion. AB - Emla cream is a eutectic mixture of lignocaine and prilocaine which can be used to anesthetize the tympanic membrane for myringotomy and ventilation tube insertion. This paper describes the anesthetic method and considers the safety and efficacy of this technique in 37 tympanic membranes from 29 adult patients. All of the patients easily tolerated the procedure. Patients with experience of previous tympanic membrane anesthetic techniques stated a preference for the Emla cream technique. No patient complained postoperatively of vertigo or tinnitus. Pure tone audiometry was performed on all 29 patients in whom a ventilation tube was inserted, both before tube insertion and at review consultation (between one month and 12 months after tube insertion. There was no audiometric evidence of ototoxicity. PMID- 1870168 TI - Autoimmune inner ear disease: a review of basic mechanisms and clinical correlates. AB - Otolaryngologists have long sought to identify causes of sensorineural hearing loss that might be reversed by medical treatment. One such entity has become known as autoimmune inner ear disease. The potential improvement in auditory function in these patients subsequent to immunosuppressive therapy has created a desire in clinicians to better understand this disease. This paper begins by reviewing the basic concepts of autoimmunity. The experimental and clinical data concerning autoimmune inner ear disease are then described and analyzed. Finally, conclusions are drawn concerning our current state of understanding of this disease process. PMID- 1870169 TI - The cochlear implant: a comparison of single-channel and multichannel results. AB - We have performed 39 cochlear implants at St. Paul's Hospital since 1982. Fourteen patients received a House/3M implant and 23 patients received a total of 25 multichannel Nucleus implants. We present a comparison of subjective and objective results in seven patients who first received a single channel implant and were subsequently implanted with a multichannel device. We also report in detail results obtained by a 55-year-old man who received a House/3M implant and subsequently received bilateral Nucleus implants. Results in this patient demonstrate some factors that influence successful use of an implant. PMID- 1870170 TI - CSF otorrhea complicating osteoradionecrosis of the temporal bone. AB - Osteoradionecrosis of the temporal bone is a well-recognized complication of radiotherapy for head and neck malignancy. There are two mechanisms by which this condition can produce damage to nearby structures and even result in death. Osteoradionecrosis may (1) predispose the patient to an aggressive or chronic infectious process, or (2) cause destruction of tissue by direct necrosis. A review of the literature failed to disclose a cause of CSF otorrhea complicating osteoradionecrosis of the temporal bone. This paper describes a case of skull base osteoradionecrosis, including necrosis of the tympanic membrane, associated with CSF otorrhea. Successful control of this complication was achieved using a translabyrinthine approach to locate the fistula, which originated from the internal auditory canal and was discharging through the middle ear via the oval window. The leak was sealed, the resultant mastoid cavity was obliterated by rotation of a temporalis muscle flap, and the external auditory canal was closed by the Fisch technique. PMID- 1870171 TI - The organic composition of earwax. AB - Earwax is a mixture of desquamated keratinocytes and hair combined with the secretions of both the ceruminous and the sebaceous glands of the external ear canal. This study analyzed earwax using the combination analytical technique of gas chromatography and mass spectrometry. The major organic components of earwax identified were long chain fatty acids, both saturated and unsaturated, alcohols, squalene and cholesterol. This study demonstrated that it is not currently possible to quantify statistically the substances which constitute earwax with accuracy. The presence of foreign substances within earwax was identified as a complicating factor in the analysis of earwax. PMID- 1870172 TI - Ossicular erosion by cholesteatoma: investigation by scanning electron microscopy utilizing a new preparation technique. AB - A new technique for removing the soft tissues from middle ear ossicles to prepare them for scanning electron microscopy is described. The technique involved use of a solution of hypochlorite. The bony surface of normal ossicles was studied as a control group after preparation by the technique and no morphological distortion was observed. Ossicles eroded by cholesteatoma were then studied, and we propose that the erosion occurs in three stages; pumicing, pitting and cavitating. The mucoperiosteum of normal ossicles and otosclerotic foci were also studied. PMID- 1870173 TI - Osteoma of the mastoid bone. PMID- 1870174 TI - Schliemann, Schwartze, Virchow and the unusual Christmas present. PMID- 1870175 TI - New method of adult transcranial Doppler. AB - Prior to development of better resolution duplex Doppler systems, blood flow velocities of the middle cerebral artery, anterior cerebral artery, and posterior cerebral artery were obtained in a "blind" manner, ie, the vessels were not imaged. We performed duplex transcranial Doppler examinations on 13 healthy volunteers and obtained peak velocities as well as resistive indices on all three arteries. The vessels were identified by their anatomic locations with respect to the brainstem and by the echogenic pulsating structures. This duplex transcranial Doppler examination holds promise for improving reproducibility and for detecting pathologic vascular states. PMID- 1870176 TI - Towards a more colorful future. PMID- 1870177 TI - Sonographic recognition of intraparenchymal regenerating nodules using high frequency transducers in patients with cirrhosis. AB - In 38 patients with cirrhotic liver, an ultrasound examination was carried out by using 3/3.5-, 5-, and 7.5-MHz transducers sequentially in order to identify hypoechoic intraparenchymal regenerating nodules less than or equal to 20 mm. Twenty healthy subjects and 35 patients with noncirrhotic chronic liver disease were scanned as controls. Focal lesions were disclosed in five patients: one case turned out to be a small hepatocellular carcinoma; regenerating nodules were diagnosed as such in four cases by means of surgery, laparoscopy, and fine needle biopsy. At a follow-up needle biopsy one year later, one of these nodules proved to be malignant. Use of high-frequency transducers offered little aid to the diagnosis of small nodules. In only one case were multiple lesions revealed with a 7.5-MHz probe but not with 3- and 5-MHz probes. It seems that intraparenchymal regenerating nodules are rarely seen with the available technology, and their recognition cannot be recommended as a reliable ultrasound diagnostic marker of liver cirrhosis. PMID- 1870178 TI - Emphysematous pyelonephritis: complementary role of radionuclide scans with ultrasound and computed tomography. PMID- 1870179 TI - Arteriovenous malformations. Locations and evolution in the fetal brain. AB - Almost all cerebral arteriovenous malformations in the fetus involve the vein of Galen, although occasionally they may involve the frontal area of the brain instead. In all reported cases arteriovenous malformations have presented some time after 30 weeks as a sonolucent oval lesion located in the midline behind the third ventricle. Previous scans have been normal. Evidence of high output failure such as cardiomegaly, enlarged neck veins, or hydrops predicts a poor outcome. PMID- 1870180 TI - Embryonic heart rate in human pregnancy. AB - Seventy-two women with known gestational ages underwent serial human chorionic gonadotropin (hCG) measurements and transvaginal ultrasound studies with embryonic heart rate measurements. In 53 continuing singleton pregnancies, embryonic pulse appeared between days 26 and 32, was 80 beat per minute (bpm) on day 26, and increased linearly to plateau at 160-200 bpm by day 45 (r2 = 0.72). The pulse was always seen with hCG greater than 21,000 mIU/mL; pulse rate was correlated to embryonic crown-rump length. Of the remaining 19 pregnancies, 8 were anembryonic, 10 showed heart activity but subsequently aborted, and 1 was terminated. Absence of embryonic pulse by 32 days after conception or a serum hCG greater than 21,000 mIU/mL predicts spontaneous abortion; presence of a pulse may not guarantee successful continuation of the pregnancy since incidence of spontaneous abortion after visualization of embryonic pulse may be as high as 16%. PMID- 1870181 TI - Noninvasive evaluation of vertebrobasilar insufficiency. AB - The diagnosis of vertebrobasilar insufficiency (VBI) is a clinical challenge because its manifestations are subjective and difficult to quantify. We evaluate 61 patients with the clinical diagnosis of VBI and 30 control patients with other medical problems. We used duplex scanning to study the extracranial carotid, vertebral, and subclavian arteries, and a 2-MHz transcranial Doppler (TCD) to examine the intracranial vertebral and basilar arteries. Extracranial lesions were more common in VBI patients than among controls, including stenosis of the subclavian artery with and without subclavian-vertebral steal and stenosis of the vertebral artery. Intracranial abnormalities identified in the vertebrobasilar circulation included stenosis and occlusion of the intracranial vertebral artery and basilar artery steal. Overall, significant lesions were detected in 32.8% of VBI patients and 3.0% of controls (P less than 0.05). Systolic artery velocity (cm/sec) in the extracranial vertebral artery was higher in controls (65.9 +/- 23.3) than in VBI patients who had no evidence of vertebrobasilar steal (43.0 +/- 17.4, P less than 0.05). Patients with a steal mechanism had an intracranial vertebral artery systolic velocity of 90.0 +/- 38.9, compared with 53.0 +/- 15.0 in controls (2P less than 0.050). Intracranial vertebral artery systolic velocity was higher among VBI patients with significant carotid artery disease (greater than 50%, 76.7 +/- 28.8) than in those with less severe disease (less than 50%, 47.3 +/- 13.8, P less than 0.05). Evaluation and quantitation of the vertebrobasilar circulation using both intra- and extracranial noninvasive studies may afford further insight as to the pathophysiology of vertebrobasilar insufficiency and provide a readily available, direct, and simple method of initial and serial assessment of VBI patients. PMID- 1870182 TI - Automatic measurements of fetal long bones. A feasibility study. AB - We investigated whether it would be possible for a computer to propose values for measurements commonly obtained (femur and humerus) during obstetrical sonography. In this preliminary study, the images were scanned and analyzed off-line using morphological operators. The procedure described allowed us to measure the long bones and has a very high coefficient of correlation with measurements obtained by humans. Ideally, the whole procedure could probably be part of the computer instructions that are built into the machine. PMID- 1870183 TI - Detection of retained products of conception following spontaneous abortion in the first trimester. AB - A retrospective analysis was performed to determine whether ultrasound could reliably rule in or out retained products of conception (POC) in women after first-trimester spontaneous abortions (miscarriages). Ninety-seven first trimester pregnancies with pathologically proven results from dilatation and curettage (D&C) were studied within 7 days of ultrasound examination (60% within 2 days), either by the abdominal or a combination of abdominal and vaginal approaches. Cases were eliminated if there was clinical evidence of a spontaneous evacuation of POC during the interval between the ultrasound and the D&C. POC were diagnosed only if chorionic villi were evident pathologically. The pertinent ultrasound findings were related to the endometrium (thickness, echogenicity, a gestational saclike structure or a space-occupying collection). The results indicated that ultrasound could correctly diagnose POC in all of the cases by detecting a gestational sac or collection (77 cases), or a thickened endometrium of greater than 5 mm (6 cases). Ultrasound was less reliable in ruling out retained POC. When only a thin endometrial stripe of less than 2 mm was present, there was little likelihood of having POC (1 of 7 cases) with a moderately thick endometrium of 2 to 5 mm not diagnostic. Vaginal ultrasound added little new information and failed to change the ultrasound interpretation. PMID- 1870184 TI - Antenatal diagnosis of vasa previa by color-flow mapping. PMID- 1870185 TI - Ultrasound diagnosis of early renal papillary necrosis. PMID- 1870186 TI - Color-flow Doppler sonography of persistent hyperplastic primary vitreous. PMID- 1870187 TI - Comparison of transabdominal and endovaginal sonographic approaches in the diagnosis of a case of cervical pregnancy successfully treated with methotrexate. PMID- 1870188 TI - In vivo accumulation of a turnip crinkle virus defective interfering RNA is affected by alterations in size and sequence. AB - Turnip crinkle virus is one of several single-stranded RNA plant viruses associated with defective interfering (DI) RNAs. A complete cDNA copy of a 344 base DI RNA (DI RNA G) was cloned downstream from a T7 RNA polymerase promoter. Transcripts synthesized in vitro were infectious when inoculated with helper virus on turnip plants. Studies of the infectivity of DI transcripts containing deletions, insertions, and single-base changes suggest that (i) in general, only the 5' two-thirds of the molecule can tolerate mutations; (ii) between 52 and 67 bases of terminal 5' sequence are required for infectivity; (iii) nucleotides in positions 68 to 138 are not specifically involved in RNA infectivity; (iv) DI RNA G molecules smaller than 327 bases are not amplified efficiently in plants. PMID- 1870189 TI - Linker insertion mutations in the adenovirus preterminal protein that affect DNA replication activity in vivo and in vitro. AB - Eighteen linker insertion mutants with mutations in the adenovirus precursor to terminal protein (pTP), which were originally constructed and tested in virions by Freimuth and Ginsberg (Proc. Natl. Acad. Sci. USA 83:7816-7820, 1986), were transferred to expression plasmids for assay of the various functions of the isolated pTP. Function was measured by the ability of individual pTP mutant proteins to participate in the initiation of replication from an adenovirus DNA end, by their activity in assays of DNA elongation, and by the intracellular distribution of pTP demonstrated by indirect immunofluorescence. Ten of the 11 mutants that were active in virion formation were also functional in DNA replication reactions in extracts, while 1 had reduced function. Four mutants with mutations that were lethal to virus production were also inactive in DNA replication reactions. These four mutations are probably located at sites required for the function of pTP in DNA synthesis. Three pTP mutants with mutations that were lethal or partially defective with respect to virion formation were active in reactions requiring pTP for initiation and elongation in extracts. All three of these mutant pTPs targeted normally to the nucleus, suggesting a defect after this step in replication. Since pTP has been reported to bind the nuclear matrix, these pTP mutants may have mutations that define sites necessary for binding to this structure. Several mutants with mutations that lie outside the putative nuclear targeting region were aberrantly localized, suggesting either that additional domains are important in nuclear localization or that there are alterations in protein structure that affect nuclear transport for some pTP mutants. PMID- 1870190 TI - Sequence analysis, expression, and deletion of a vaccinia virus gene encoding a homolog of profilin, a eukaryotic actin-binding protein. AB - A 4,500-bp BamHI fragment, located within the HindIII A segment of the vaccinia virus genome, was found to contain eight potential coding regions for polypeptides of 78 to 346 amino acids. The open reading frames with 133, 346, and 125 codons were homologous to profilin (an actin-binding protein), 3-beta hydroxysteroid dehydrogenase, and Cu-Zn superoxide dismutase, respectively. Sequence alignments indicated that the vaccinia virus and mammalian profilins were more closely related to each other than to known profilins of other eukaryotes. The expression and possible role of the profilin homolog in the virus replicative cycle were therefore investigated. Antibody raised to Escherichia coli expressed vaccinia virus profilin was used to demonstrate the synthesis of the 15-kDa polypeptide at late times after vaccinia virus infection of mammalian cells. The protein accumulated in the cytoplasm, but only trace amounts remained associated with highly purified virions. The isolation of vaccinia virus mutants (in strains WR and IHD-J), with nearly the entire profilin gene replaced by the E. coli gpt gene, indicated that the protein is not essential for infectivity. The characteristic vaccinia virus-induced changes in actin fibers, seen by fluorescence microscopy, occurred in cells infected with the mutant. Moreover, the virus-encoded profilin homolog was not required for actin-associated events, including intracellular virus movement to the periphery of the cell, formation of specialized microvilli, or release of mature virions, as shown by electron microscopy and yields of infectious intra- and extracellular virus. PMID- 1870191 TI - Utilization of DNA recombination for the two-step replacement of growth factor sequences in the vaccinia virus genome. AB - An efficient procedure for the generation of sequence-specific alterations of the vaccinia virus genome was demonstrated. Homologous DNA recombination within cells infected with vaccinia virus was used for the deletion or replacement of promoter sequences of the viral growth factor gene by a procedure comparable to transplacement in Saccharomyces cerevisiae. This DNA replacement procedure can potentially be used to generate any sequence alteration within the vaccinia virus genome. Deletion of growth factor promoter sequences resulted in a dramatic reduction in growth factor gene transcription and protein synthesis. Replacement of growth factor promoter sequences with promoter sequences of the strong constitutive 40-kDa gene resulted in an increase in gene transcription and protein synthesis and an altered temporal pattern of expression. Virus containing mutations in the growth factor gene demonstrated different plaque morphologies on cell culture monolayers. PMID- 1870193 TI - The minute virus of mice capsid specifically recognizes the 3' hairpin structure of the viral replicative-form DNA: mapping of the binding site by hydroxyl radical footprinting. AB - The terminal hairpin structures of the DNA of minute virus of mice (MVM) are essential for viral replication. Here we show that the hairpin 3' terminus of MVM replicative-form DNA binds specifically to empty MVM capsids. Binding of the same terminal DNA sequence in its linear double-stranded (extended) conformation was not observed. After heat denaturation and quick cooling of 3'-terminal extended form fragments, not only the virion strand but also the complementary strand was found to bind to the capsid, presumably because each strand re-formed a similar hairpin structure. No binding affinity for the capsid was found to be associated with hairpin or extended 5' termini or with any other region of the viral DNA. Hydroxyl radical footprinting analyses revealed three protected nucleotide stretches forming a binding site at the branch point of the two 3'-terminal hairpin arms looping out from the DNA stem (T structure). Single base changes within this site did not affect the binding. In band shift experiments, specific binding to the T structure was demonstrated for VPI but not for VP2. PMID- 1870192 TI - Characterization of endogenous and recombinant proviral elements of a highly tumorigenic AKR cell line. AB - As an approach to evaluating the contribution of classes of endogenous viral sequences to leukemogenesis, a genomic library was prepared from the highly tumorigenic AKR SL12.3 cell line and screened for env-containing proviruses. An extensive battery of virus-derived probes and specific oligonucleotide probes were used to segregate 83 positive clones into related groups. The nonecotropic endogenous retroviruses were identified as members of the polytropic, modified polytropic, or xenotropic groups. At least three unique xenotropic proviruses were detected that differed from the published xenotropic sequence within a variable region of the 5' portion of env. Changes among the xenotropic proviruses included relative insertions and/or deletions that maintain an open reading frame and hence the potential to encode viable envelope gene products. Several recombinant viruses were also detected. Recombination was not random and primarily involved the formation of mink cell focus-inducing class I retroviruses via recombination between polytropic elements and ecotropic virus. One other recombinant was detected which contained ecotropic virus sequences in the 5' region encoding p15 of an otherwise xenotropic provirus. An interesting observation was the finding that certain clones contained more than one provirus within the average 20-kb cloned insert. This would not be expected if integration were totally random. The de novo recombinant proviruses identified here provide a series of potential candidates to be evaluated for their contribution to the tumorigencity of the SL12.3 cell line. PMID- 1870194 TI - Human immunodeficiency virus integrase protein requires a subterminal position of its viral DNA recognition sequence for efficient cleavage. AB - Retroviral integration requires cis-acting sequences at the termini of linear double-stranded viral DNA and a product of the retroviral pol gene, the integrase protein (IN). IN is required and sufficient for generation of recessed 3' termini of the viral DNA (the first step in proviral integration) and for integration of the recessed DNA species in vitro. Human immunodeficiency virus type 1 (HIV-1) IN, expressed in Escherichia coli, was purified to near homogeneity. The substrate sequence requirements for specific cleavage and integration of retroviral DNA were studied in a physical assay, using purified IN and short duplex oligonucleotides that correspond to the termini of HIV DNA. A few point mutations around the IN cleavage site substantially reduced cleavage; most other mutations did not have a drastic effect, suggesting that the sequence requirements are limited. The terminal 15 bp of the retroviral DNA were demonstrated to be sufficient for recognition by IN. Efficient specific cutting of the retroviral DNA by IN required that the cleavage site, the phosphodiester bond at the 3' side of a conserved CA-3' dinucleotide, be located two nucleotides away from the end of the viral DNA; however, low-efficiency cutting was observed when the cleavage site was located one, three, four, or five nucleotides away from the terminus of the double-stranded viral DNA. Increased cleavage by IN was detected when the nucleotides 3' of the CA-3' dinucleotide were present as single stranded DNA. IN was found to have a strong preference for promoting integration into double-stranded rather than single-stranded DNA. PMID- 1870195 TI - Genetic analysis of the DNA recognition sequence of the P2 Cox protein. AB - The Cox protein of temperate Escherichia coli phage P2 is involved in three important biological processes: (i) excision of the integrated prophage genome (G. Lindahl and M. Sunshine, Virology 49:180-187, 1972), (ii) transcriptional repression of the P2 Pc promoter, which controls the expression of the immunity repressor C and the integrase (S. Saha, E. Haggard-Ljungquist, and K. Nordstrom, EMBO J. 6:3191-3199, 1987), and (iii) transcriptional activation of the late PII promoter of the unrelated satellite phage P4 (S. Saha, E. Haggard-Ljungquist, and K. Nordstrom, Proc. Natl. Acad. Sci. USA 86:3973-3977, 1989). A comparison of the DNA regions protected by Cox from DNaseI degradation has revealed a presumptive Cox recognition sequence (Saha et al., Proc. Natl. Acad. Sci. USA). The binding region of Cox in the P2 Pc promoter contains three presumptive recognition sequences, "Cox boxes," located in tandem. P2 vir3 and P2 vir24 are virulent deletion mutants unable to plate on Cox-producing strains, most likely because the deletions locate the new early promoters too close to the Cox-binding region (Saha et al., EMBO J.). In this report, spontaneous P2 vir3 and vir24 mutants, no longer sensitive to repression by the Cox protein, have been isolated. These mutants plate with equal efficiency on strains with or without a Cox-producing plasmid, and they have been named cor for cox resistance. Three types are recognized; the four P2 vir3 cor mutants have a 1-base deletion in the first Cox box, while the P2 vir24 cor mutants were of two types; four have a base substitution in the first Cox box, and one has a base substitution in the second Cox box. The effect of the Cox protein on the mutated P2 vir3 and vir24 promoters was analyzed in vivo by using fusions to a promoterless cat (chloramphenicol acetyltransferase) gene. The activities of the P2 vir3 and vir24 early promoters, as opposed to the wild-type early Pe promoter, are drastically reduced by the Cox protein, and the cor mutation renders them as resistant to Cox as the wild-type Pe promoter. Thus, at least the first two Cox boxes are essential for binding of the Cox protein. PMID- 1870196 TI - A single point mutation activates the Moloney murine leukemia virus long terminal repeat in embryonal stem cells. AB - The expression of Moloney murine leukemia virus (Mo-MuLV) and Mo-MuLV-derived vectors is restricted in undifferentiated mouse embryonal carcinoma and embryonal stem (ES) cells. We have previously described the isolation of retroviral mutants with host range properties expanded to embryonal cell lines. One of these mutants, the murine embryonic stem cell virus (MESV), is expressed in ES cell lines. Expression of MESV in these cells relies on DNA sequence motifs within the enhancer region of the viral long terminal repeat (LTR). Here we show that replacement of the Mo-MuLV enhancer region by sequences derived from the MESV LTR results in the activation of the Mo-MuLV LTR in ES cells. The enhancer regions of MESV and Mo-MuLV differ by seven point mutations. Of these, a single point mutation at position -166 is sufficient to activate the Mo-MuLV LTR and to confer enhancer-dependent expression to Mo-MuLV-derived retroviral vectors in ES cells. This point mutation creates a recognition site for a sequence-specific DNA binding factor present in nuclear extracts of ES cells. This factor was found by functional assays to be the murine equivalent to human Sp1. PMID- 1870197 TI - Identification of the hepatitis B virus factor that inhibits expression of the beta interferon gene. AB - The identity of the trans-acting factor encoded by the 1,828-bp BamHI DNA fragment of hepatitis B virus (HBV) that suppresses the transcription of the human beta interferon gene was investigated. Each complete and partial open reading frame (ORF) present within the 1,828-bp BamHI HBV DNA fragment was cloned into a simian virus 40 expression vector, and the resulting gene products were assayed for their ability to inhibit the activity of the regulatory DNA region that governs the expression of the beta interferon gene. Only the proteins encoded by the C ORF inhibited the activity of the beta interferon regulatory DNA region; putative proteins encoded by the partial X, P, and S ORFs present in the 1,828-bp BamHI HBV DNA fragment had no effect. A plasmid encoding only the native HBV core antigen, but not one coding for a truncated core antigen, possessed this inhibitory activity. The inhibition by the core antigen was specific for the regulatory elements of the beta interferon gene; none of a variety of viral transcriptional elements was inhibited. PMID- 1870198 TI - Hog cholera virus: molecular composition of virions from a pestivirus. AB - Virions from hog cholera virus (HCV), a member of the genus Pestivirus, were analyzed by using specific antibodies. The nucleocapsid protein was found to be a 14-kDa molecule (HCV p14). An equivalent protein could also be demonstrated for virions from another pestivirus, bovine viral diarrhea virus. The HCV envelope is composed of three glycoproteins, HCV gp44/48, gp33, and gp55. All three exist in the form of disulfide-linked dimers in virus-infected cells and in virions; HCV gp44/48 and gp55 each form homodimers, whereas gp55 is also found dimerized with gp33. Such complex covalent interactions between structural glycoproteins have not been described so far for any RNA virus. PMID- 1870199 TI - RGD-dependent entry of coxsackievirus A9 into host cells and its bypass after cleavage of VP1 protein by intestinal proteases. AB - The recently reported nucleotide sequence of coxsackievirus A9 (CAV-9) showed that unlike other enteroviruses, CAV-9 has an insertion of about 17 amino acids at the C-terminal end of VP1 (K. H. Chang, P. Auvinen, T. Hyypia, and G. Stanway, J. Gen. Virol. 70:3269-3280, 1989). This sequence includes the RGD (arginine glycine-aspartic acid) motif which is known to be important in certain protein protein interactions. We studied the inhibitory effect of RGD-containing peptides in the attachment of CAV-9 to African green monkey kidney cells. A peptide corresponding to the RRGDM sequence derived from the inserted segment of CAV-9 was found to block virus attachment effectively, and the inhibition was dose dependent. Substitution of glutamic acid for the homologous aspartic acid completely abolished the inhibitory effect, indicating great specificity of the action. During replication in the gut, all enteroviruses are exposed to host proteolytic enzymes. Exposure of CAV-9 to purified trypsin or human intestinal fluid resulted in selective cleavage of the VP1 capsid protein. Intact and trypsin-cleaved VP1 proteins gave identical N-terminal sequences, indicating that cleavage of VP1 takes place near the C terminus. Attachment of proteolytically cleaved infectious CAV-9 to green monkey kidney cells was not prevented by RGD containing peptides, indicating that cleaved CAV-9 is able to bypass RGD dependent entry. The altered receptor specificity of proteolytically cleaved viruses may have important consequences in the pathogenesis of enteric infections. PMID- 1870200 TI - Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes. AB - With the rationale that the neuropathological similarities between scrapie and Alzheimer's disease reflect convergent pathological mechanisms involving altered gene expression, we set out to identify molecular events involved in both processes, using scrapie as a model to study the time course of these changes. We differentially screened a cDNA library constructed from scrapie-infected mice to identify mRNAs that increase or decrease during disease and discovered in this way two mRNAs that are increased in scrapie and Alzheimer's disease. These mRNAs were subsequently shown by sequence analysis to encode apolipoprotein E and cathepsin D (EC 3.4.23.5). Using in situ hybridization and immunocytochemistry to define the cellular and anatomic pathology of altered gene expression, we found that in both diseases the increase in apolipoprotein E and cathepsin D mRNAs and proteins occurred in activated astrocytes. In scrapie, the increase in gene expression occurred soon after the amyloid-forming abnormal isoform of the prion protein has been shown to accumulate in astrocytes. In Alzheimer's disease, the increased expression of cathepsin D also occurred in association with beta amyloid. These studies reveal some of the molecular antecedents of neuropathological changes in scrapie and Alzheimer's disease and accord new prominence to the role of astrocytes in neurodegenerative conditions. PMID- 1870201 TI - Spleen necrosis virus, an avian retrovirus, can infect primate cells. AB - Spleen necrosis virus (SNV) is an avian retrovirus that can infect some mammalian cells such as dog cells as well as all avian cells tested to date. We were interested in testing whether SNV could also infect primate cells. For these experiments, we used HeLa and COS-7 cells. Initially, we determined whether the SNV long terminal repeat promoter was functional in HeLa and COS-7 cells. In transient transfection assays, the SNV promoter efficiently directed chloramphenicol acetyltransferase gene expression in both HeLa and COS-7 cells. Using SNV- and murine leukemia virus-derived retroviral vectors containing the neomycin phosphotransferase gene, we found that SNV established a provirus in HeLa and COS-7 cells as efficiently as did an amphotropic murine leukemia virus, as judged by the number of G418-resistant HeLa and COS-7 cell colonies obtained after infection and selection. Although SNV formed a provirus in both HeLa and COS-7 cells, productive infection of these cells was not obtained with use of replication-competent SNV. These results suggest that SNV can infect, form a provirus, and stably express a transduced gene in primate cells, but there is a posttranscriptional block to its replication in these cells. PMID- 1870202 TI - Recombinant CD4-selected human immunodeficiency virus type 1 variants with reduced gp120 affinity for CD4 and increased cell fusion capacity. AB - Variants of molecularly cloned human immunodeficiency virus type 1 (HIV-1) were analyzed following selection for the ability to replicate after exposure to soluble, recombinant CD4 protein (rCD4). Two variants, 4/1 and 16/2, show 8-fold and 16-fold reduced sensitivity to rCD4 neutralization yet remain as sensitive as the parental wild-type (wt) virus to neutralization by rCD4-immunoglobulin G (IgG) chimeric molecules and to inhibition of cellular infection by anti-CD4 antibody. The 4/1 variant is more cytopathic, with faster cell fusion and replication kinetics than the wt virus. The gp120s derived from the 4/1 and 16/2 variants have 3-fold and 30-fold reduced binding affinities to rCD4, respectively. The 4/1 variant exhibits diminished shedding of virion gp120 induced by rCD4. The binding of and neutralization by V3 loop antibodies and other anti-gp120 antibodies is reduced for 4/1 but not for 16/2. Sequence analysis revealed a codon change at amino acid residue 435 in the C4 region of the gp120 of 16/2. This accounts for its rCD4 insensitivity, since the insertion of this mutation in the wt gp120 yields the same phenotype. The 4/1 variant has a codon change in the V3 region of gp120 (amino acid 311), which accounts for its reduced sensitivity to some neutralizing antibodies but not to rCD4. The ready selection of rCD4-resistant variants has obvious relevance for rCD4-based therapeutic stratagems. PMID- 1870203 TI - Synthesis and characterization of chimeric particles between epizootic hemorrhagic disease virus and bluetongue virus: functional domains are conserved on the VP3 protein. AB - A functional assay has been developed to determine the conservative nature of the interacting sites of various structural proteins of orbiviruses by using baculovirus expression vectors. For this investigation, proteins of two serologically related orbiviruses, bluetongue virus (BTV) and the less studied epizootic hemorrhagic disease virus (EHDV), were used to synthesize chimeric particles. The results demonstrate that the inner capsid protein VP3 of EHDV-1 can replace VP3 protein of BTV in formation of the single-shelled corelike particles and the double-shelled viruslike particles. Moreover, we have demonstrated that all three minor core proteins (VP1, VP4, and VP6) can be incorporated into the homologous and chimeric corelike and viruslike particles, indicating that the functional epitopes of the VP3 protein are conserved for the morphological events of the virus. This is the first evidence of assembly of seven structural proteins of the virus by a baculovirus expression system. Confirmation at the molecular level was obtained by determining the EHDV-1 L3 gene nucleic sequence and by comparing it with sequences available for BTV. The analysis revealed a high degree homology between the two proteins: 20% difference, 50% of which is conservative. The consequences for Orbivirus phylogeny and the possibility of gene reassortments are discussed. PMID- 1870204 TI - Reversible conformational changes and fusion activity of rabies virus glycoprotein. AB - In an attempt to understand the implication of the rabies virus glycoprotein (G) in the first steps of the viral cycle, we studied the pH dependence of virus induced fusion and hemagglutination, as well as modifications of the structure and properties of the viral glycoprotein following pH acidification. Our results suggest that the G protein adopts at least three distinct configurations, each associated with different properties. At neutral pH, G did not fuse membranes or hemagglutinate erythrocytes. It was insensitive to digestion with bromelain and trypsin. At pH 6.4, the glycoprotein became sensitive to proteases. Hemagglutination was at its maximum and then sharply decreased with the pH. No fusion was detected. Aggregation of virus was also observed. The third configuration, at below pH 6.1, was associated with the appearance of fusion. Some neutralizing monoclonal antibodies were able to differentiate these three configurations. Preincubation of the virus at below pH 6 inhibited fusion, but this inhibition, like the structural modifications of the glycoprotein, was reversible when G was reincubated at neutral pH. PMID- 1870205 TI - Replication of an acutely lethal simian immunodeficiency virus activates and induces proliferation of lymphocytes. AB - A variant of simian immunodeficiency virus from sooty mangabey monkeys (SIVsmm), termed SIVsmmPBj14, was previously identified and shown to induce acute disease and death within 1 to 2 weeks of inoculation of pig-tailed macaques and mangabey monkeys (P. N. Fultz, H. M. McClure, D. C. Anderson, and W. M. Switzer, AIDS Res. Hum. Retroviruses 5:397-409, 1989). SIVsmmPBj14 differed from its parent virus, SIVsmm9, not only in pathogenicity but also in multiple in vitro properties. As a first approach to understanding the biological and molecular mechanisms responsible for the acute disease and death induced by this variant, virus-host cell interactions of SIVsmmPBj14 and SIVsmm9 were studied. Initial rates of replication of the two viruses were identical in primary peripheral blood mononuclear cells (PBMC) from normal pig-tailed macaques and mangabey monkeys, but SIVsmmPBj14 infection always resulted in higher yields of virus than did SIVsmm9 infection, as assessed by levels of reverse transcriptase activity in culture supernatants. Surprisingly, despite its cytopathicity for macaque and mangabey CD4+ cells, replication of SIVsmmPBj14 was accompanied by up to 10-fold increases in number of viable cells compared with cell numbers in uninfected or SIVsmm9-infected cultures. Furthermore, SIVsmmPBj14 was shown to infect and replicate in resting PBMC just as efficiently as in mitogen-stimulated PBMC, irrespective of whether exogenous interleukin-2 (IL-2) or antibodies that neutralized IL-2 were added to culture media. Accumulation of virus in culture supernatants of resting PBMC preceded by several days the appearance of activated cells which expressed the IL-2 receptor alpha subunit (CD25), suggesting that activation of cells was not essential for replication. The ability to activate and to induce simian PBMC to proliferate appeared specific for the acutely lethal variant because incorporation of [3H]thymidine by PBMC from naive animals was observed only upon incubation with concentrated, heat-inactivated SIVsmmPBj14 and not with other viruses. Both CD4(+)- and CD8(+)-enriched cell populations proliferated in response to SIVsmmPBj14. These results are consistent with in vivo observations and suggest that the abilities both to replicate in resting cells and to induce lymphocytes to proliferate may contribute to the extreme virulence of SIVsmmPBj14. PMID- 1870206 TI - Transcriptional elongation by purified RNA polymerase II is blocked at the trans activation-responsive region of human immunodeficiency virus type 1 in vitro. AB - It has previously been shown that the human immunodeficiency virus type 1 (HIV-1) trans-activation-responsive region (TAR) is contained in a stem-loop RNA structure. Moreover, the interaction of the RNA secondary structure with Tat, the trans-activator protein, seems to play a role in activation of transcription initiation and in preventing transcription attenuation. In this work, we have studied the ability of the HIV-1 TAR stem-loop to act as a specific attenuation signal for highly purified RNA polymerase II. We developed an in vitro system using dC-tailed DNA fragments of HIV-1 to study transcriptional control in the HIV-1 LTR. We have found that transcription in this system yields an attenuator RNA whose 3' end maps to the end of the TAR stem-loop, approximately 60 to 65 nucleotides downstream of the in vivo initiation site. Furthermore, transcription attenuation occurs only under conditions which cause displacement of the nascent transcript from the template DNA strand, thus allowing the RNA to fold into secondary structure. Evidence is provided that the purified polymerase II indeed recognizes stable RNA secondary structure as an intrinsic attenuation signal. The existence of this signal in the TAR stem-loop suggests that in vivo an antiattenuation factor, probably Tat, alone or in combination with other factors, acts to relieve the elongation block at the HIV-1 attenuation site. PMID- 1870207 TI - Activation of the c-ski oncogene by overexpression. AB - The v-ski oncogene is a truncated version of the cellular proto-oncogene, c-ski, and lacks sequences coding for both the N- and C-terminal ends of the c-ski protein. In the region of overlap, v-ski and c-ski differ by only one amino acid. To determine whether these differences underlie v-ski's oncogenic activation, we have cloned cDNAs for several alternatively spliced c-ski mRNAs and introduced these cDNAs into replication-competent retroviral vectors. The biological activities of these c-ski constructs have been compared with those of v-ski. We found that all c-ski gene products, when expressed at high levels from the promoter in the retroviral long terminal repeat, can induce morphological transformation, anchorage independence, and muscle differentiation in avian cells. Cells that are susceptible to ski-induced transformation and myogenesis normally express endogenous c-ski at low levels. Thus, it appears that overexpression of ski is sufficient for oncogenic and myogenic activation. PMID- 1870208 TI - Purification and characterization of human papillomavirus type 16 E7 protein with preferential binding capacity to the underphosphorylated form of retinoblastoma gene product. AB - Human papillomavirus type 16 E7 is considered to be a major viral oncoprotein playing an important role(s) in cervical cancers. E7 protein was shown to bind to the protein product of the retinoblastoma gene (RB), while simian virus 40 large T and adenovirus E1A were also shown to possess binding activity to RB protein. The RB protein is a cell cycle regulator that is highly phosphorylated specifically in S, G2, and M, whereas it is underphosphorylated in G0 and G1. Recently, large T was demonstrated to bind preferentially to the underphosphorylated RB protein, which is considered to be an active form restricting cell proliferation. However, it is not known whether E7 can bind to phosphorylated RB protein. We successfully purified large quantities of unfused human papillomavirus type 16 E7 protein expressed in Escherichia coli by using a T7 promoter-T7 RNA polymerase system. The purified E7 protein was demonstrated to bind preferentially to the underphosphorylated RB protein. PMID- 1870209 TI - Effects of changes in gp120-CD4 binding affinity on human immunodeficiency virus type 1 envelope glycoprotein function and soluble CD4 sensitivity. AB - Mutant gp120 glycoproteins exhibiting a range of affinities for CD4 were tested for ability to form syncytia and to complement an env-defective provirus for replication. Surprisingly, gp120 mutants that efficiently induced syncytia and/or complemented virus replication were identified that exhibited marked (up to 50 fold) reductions in CD4-binding ability. Temperature-dependent changes in gp120, which result in a seven- to ninefold increase in affinity for CD4, were shown not to be necessary for subsequent membrane fusion or virus entry events. Mutant glycoproteins demonstrating even relatively small decreases in CD4-binding ability exhibited reduced sensitivity to soluble CD4. The considerable range of CD4-binding affinities tolerated by replication-competent HIV-1 variants has important implications for antiviral strategies directed at the gp120-CD4 interaction. PMID- 1870210 TI - Identification of two distinct regions within the adenovirus minimal origin of replication that are required for adenovirus type 4 DNA replication in vitro. AB - The adenovirus type 4 origins of replication are located at each end of the linear, protein-linked viral DNA molecule and consist of the terminal 18 bp of the viral genome. The sequence of the first 8 bp of the viral genome varies among different adenovirus serotypes, but the sequence from bp 9 to 18 is conserved in all human serotypes, suggesting that it may be of critical importance to origin function. Using an in vitro system in which purified fractions or crude extracts of adenovirus type 4-infected HeLa cells can support initiation and elongation on linearized plasmid templates containing cloned origin sequences, we examined the effect of single base changes in positions 9 to 18 of the adenovirus origin on DNA replication in vitro. Changes in positions 12 to 16 have little effect, whereas alterations at positions 9, 10, 11, 17, and 18 all reduce the efficiency of initiation of DNA replication by between 50 and 90%. Our results show that the region from bp 9 to 18 contains two sets of bases essential for DNA replication which are separated by 5 bp in which single base changes can be accommodated. The likely role of the region from bp 9 to 18 as containing the recognition sequence for a DNA-protein interaction essential for viral DNA replication is discussed. PMID- 1870211 TI - Antibody enhancement of respiratory syncytial virus stimulation of leukotriene production by a macrophagelike cell line. AB - The clinical and epidemiologic features of respiratory syncytial virus (RSV) infections suggest that RSV-specific antibody may sometimes contribute to the disease process. Recently, it has been demonstrated that virus-specific antibody can enhance RSV infection of macrophagelike cells in vitro. We evaluated the possibility that antibody might also enhance RSV stimulation of the bronchoactive mediator of inflammation leukotriene C-4 (LTC4)in a macrophagelike cell line, U937. The addition of RSV led to little increase in LTC4 production, but addition of RSV plus anti-RSV antibody increased production to a level similar to that achieved with calcium ionophore, a known stimulator of LTC4 production. The antibody-enhanced increase in LTC4 production occurred rapidly (within 15 min), peaked at 60 min, and achieved levels 1.5- to 3.0-fold above that for cells or cells plus virus. RSV plus anti-RSV antibodies in the form of polyclonal serum, monoclonal antibodies, or F(ab')2 fragments and parainfluenza virus types 1 and 3 plus their respective antibodies all increased LTC4 levels over that for the virus alone. These results demonstrate that antibody plus the corresponding virus or protein can increase leukotriene production. This phenomenon could contribute to diseases, such as RSV bronchiolitis, that appear to be caused by an interaction between the virus (or antigen) and host immunity. PMID- 1870212 TI - Proteolytic conversion of hepatitis B virus e antigen precursor to end product occurs in a postendoplasmic reticulum compartment. AB - At least two proteolytic events are involved in the biogenesis of hepatitis B virus e antigen. The first proteolytic event removes the signal peptide and results in the translocation of the precursor protein, P22, into the lumen of the endoplasmic reticulum (ER). The second proteolytic event removes the carboxy terminal arginine-rich sequence of P22 and converts it to the 16-kDa hepatitis B virus e antigen end product. In contrast to the first proteolytic event, the second proteolytic event is suppressed by brefeldin A, a chemical that inhibits the transport of protein from the ER to the Golgi apparatus. In subcellular fractionation experiments, P22 was detected in both the ER and the Golgi fractions, but P16 was detected only in the Golgi fraction. On the basis of these results, we conclude that the conversion of P22 to P16 occurs ina post-ER compartment, mostly likely the Golgi apparatus. PMID- 1870213 TI - Cytopathic variants of an attenuated isolate of human immunodeficiency virus type 2 exhibit increased affinity for CD4. AB - Naturally occurring isolates of human immunodeficiency virus (HIV) have been described which are deficient in their ability to fuse with and kill CD4+ target cells. Although the molecular basis for their attenuation has not yet been defined, several lines of evidence point toward the viral envelope gene as a key determinant of viral pathogenicity. In the present article, we report the biological characterization of two highly cytopathic variants derived by repeated cell-free passage of an attenuated isolate of HIV type 2 (HIV-2), termed HIV 2/ST. Unlike the parental virus, the cytopathic variants were found to infect Sup T1 cells with great efficiency and to induce both cell fusion and profound killing in these cultures. To determine whether changes in the viral envelope gene were responsible for the observed phenotypic differences, we examined the CD4 binding affinity of these viruses using a novel assay designed to quantitate the binding of fluoresceinated CD4 to viral envelope in its native configuration on the cell surface. The results demonstrated that the affinity of parental HIV 2/ST envelope for CD4 was 2 orders of magnitude reduced, while the cytopathic variants exhibited a high CD4 binding affinity, comparable to that of cytopathic HIV-1 and HIV-2 isolates. From these data, we conclude that the cytopathic potential of HIV depends, at least in part, on its receptor-binding affinity. In addition, our study documents strong selection pressures for viruses with increased CD4 affinity during propagation in immortalized T-cell lines, thus emphasizing the need to study HIV envelope biology in natural target cells. PMID- 1870214 TI - The Lang strain of reovirus serotype 1 and the Dearing strain of reovirus serotype 3 differ in their sensitivities to beta interferon. AB - Replication of the Dearing strain of reovirus serotype 3 in mouse L cells was decreased 17- to 100-fold when a saturating dose of beta interferon (1,000 IU/ml) was used. Replication of the Lang strain of reovirus serotype 1 was inhibited only two- to threefold under similar conditions. It therefore appears that closely related strains of reovirus differ in their sensitivities to beta interferon treatment of mouse L cells. PMID- 1870215 TI - Overexpression of the gag-pol precursor from human immunodeficiency virus type 1 proviral genomes results in efficient proteolytic processing in the absence of virion production. AB - The expression of the gag-pol polyprotein of human immunodeficiency virus type 1 (HIV-1) occurs via ribosomal frameshifting between the gag and pol genes. Because low levels of the gag-pol precursor are naturally produced in HIV-1-infected cells, a limited amount of information is available on the biology of this molecule. To further study this polyprotein, two mutant HIV-1 proviral genomes were created to position the gag and pol genes in the same translational reading frame. The mutations inserted a single thymidine nucleotide at the site of ribosomal frameshifting (nucleotide 1635), which results in the addition of a phenylalanine residue (frameshift 1 [FS1]), or a single adenine nucleotide, which results in the addition of a leucine residue (frameshift 2 [FS2]). Transfection of the mutant proviral genomes into COS-1 cells resulted in the expression of the p160gag-pol polyprotein precursor as well as the proteolytically processed gag and pol gene products. Metabolic labeling of the transfected cells with [3H]myristic acid revealed that the p160gag-pol and p17gag proteins expressed from the mutant genomes were myristylated. While the supernatants from COS-1 cells transfected with wild-type or mutant proviral genomes contained similar amounts of p24 antigen, the levels of reverse transcriptase were, on the average, 10 times greater in the supernatants from cells transfected with the FS1 and FS2 proviral genomes. The cells transfected with the wild-type proviral genome released infectious viral particles, while the mutant proviral genomes released p24 and reverse transcriptase in the absence of detectable particle formation. The mutant proviral genomes were completely noninfectious as determined by coculture of the transfected COS-1 cells with SupT1 cells. These results demonstrate that the gag-pol polyprotein of HIV-1 contains the appropriate signals for proteolytic processing and association with intracytoplasmic membranes in the absence of virion formation. PMID- 1870216 TI - A nested set of eight RNAs is formed in macrophages infected with lactate dehydrogenase-elevating virus. AB - Total RNA was extracted from primary cultures of mouse macrophages isolated from 10-day-old mice 6 to 12 h postinfection with lactate dehydrogenase-elevating virus (LDV). Poly(A)+ RNA was extracted from spleens of 18-h LDV-infected mice. The RNAs were analyzed by Northern (RNA) blot hybridization with a number of LDV specific cDNAs as probes. A cDNA representing the nucleocapsid protein (VP-1) gene located at the 3' terminus of the viral genome (E. K. Godeny, D. W. Speicher, and M. A. Brinton, Virology 177:768-771, 1990) hybridized to viral genomic RNA of about 13 kb plus seven subgenomic RNAs ranging in size from about 1 to about 3.6 kb. Two other cDNA clones hybridized only to the four or five largest subgenomic RNAs, respectively. In contrast, two cDNAs encoding continuous open reading frames with replicase and zinc finger motifs hybridized only to the genomic RNA. The replicase motif exhibited 75% amino acid identity to that of the 1b protein of equine arteritis virus (EAV) and 44% amino acid identity to those of the 1b proteins of coronaviruses and Berne virus. Combined, the results indicate that LDV replication involves formation of a 3'-coterminal-nested set of mRNAs as observed for coronaviruses and toroviruses as well as for EAV, with which LDV shares many other properties. Overall, LDV, like EAV, possesses a genome organization resembling that of the coronaviruses and toroviruses. However, EAV and LDV differ from the latter in the size of their genomes, virion size and structure, nature of the structural proteins, and symmetry of the nucleocapsids. PMID- 1870218 TI - Medical schools in Canada. PMID- 1870217 TI - Medical schools in the United States. PMID- 1870219 TI - E. Grey Dimond, MD--the 'counterculture' medical educator. PMID- 1870220 TI - A piece of my mind. Educational malpractice. PMID- 1870221 TI - Educational programs in US medical schools. AB - One noteworthy finding for the 1990-1991 academic year is the increasing number of applicants to medical school, coupled with stabilization in the credentials of accepted applicants. This increase appears to be reversing the downward trend of the 1980s. The percentages of women and total minority students in the entering class increased from the previous year. The prevalence of instructional formats such as problem-based learning and computer-assisted instruction illustrates that medical schools are willing to experiment with educational innovation. A number of schools are in the process of curriculum review, which may lead to important changes. The financial support offered by private foundations interested in curriculum innovation, for some, will be an added stimulus for change. While the majority of medical schools continue to require that students take the examinations and the subject tests of the NBME, evaluation formats that test clinical skills are receiving increased attention. The number of schools using multiple station examinations (often with standardized patients) is rising. The impact of the new US Medical Licensing Examination on medical school curricula should be analyzed in the future. Although steady increases have been reported in the number of medical school faculty members, especially clinical faculty, there is little information about how these faculty members apportion their time between teaching, research, and patient care. The assumption is that the increases are primarily driven by medical schools' need to provide clinical services, which are a source of income. Another explanation for faculty increases could relate to the need for more faculty involvement in educational innovations such as problem-based learning and new methods of clinical skills evaluation, which are relatively more faculty-intensive. Continued monitoring of the growth in clinical faculty will be necessary, as will more careful analysis of how medical school faculty spend their time. Since medical school faculty who have heavy involvements in teaching frequently do not receive appropriate recognition or reward, it will also be interesting to examine the effectiveness of diverse incentives used by the schools to reward teaching faculty. An appropriate reward system for teaching is important if undergraduate medical education is to command a high priority in institutions awarding the doctor of medicine degree. PMID- 1870222 TI - Selected characteristics of graduate medical education in the United States. AB - For the second year, the Department of Data Systems in the Medical Education Group of the American Medical Association gathered information on graduate medical education primarily by means of an electronic data collection system. Eighty-eight percent of 6622 programs surveyed responded, with 83% reporting detailed information on residents. Analysis of graduate medical education data shows that the number of residents increased by 34.9% from the academic years 1980-1981 to 1990-1991, while the number of graduate year 1 residents decreased by 2%. In the same decade, the proportion of women residents increased by 7.1%. The number of minorities in graduate medical education has grown, but their proportions within the total resident population have remained largely unchanged. The number of graduates from schools of osteopathic medicine has increased by 265% over the same 10-year period. Between 1989 and 1990, a 31.6% increase was recorded in the number of international medical graduates in graduate year 1 residency positions; most of this increase (63.4%) occurred among noncitizens of the United States. PMID- 1870223 TI - Refocusing support and direction. PMID- 1870224 TI - Licensure and international medical graduates. PMID- 1870225 TI - Student attrition. A challenge for allied health education programs. AB - The Committee on Allied Health Education and Accreditation (CAHEA) attrition data, collected annually by the American Medical Association (AMA), are nationally representative and constitute the largest source of information on attrition and retention in allied health education. These data provide a cornerstone for education and manpower planning. Consistent with previous years, men who were enrolled in CAHEA-accredited allied health education programs for the 1989-1990 academic year were significantly more likely to be lost to attrition than were women. When compared with all other categories of race and ethnic origin, black students not of Hispanic origin showed a significantly higher attrition rate (25.4%), while students designated as Asian or Pacific Islander showed a significantly lower rate (13%). Congruent with attrition data documented in the literature, CAHEA attrition data show wide variances across 26 allied health occupations and within the three disciplinary groupings that comprise approximately 75% of all CAHEA-accredited programs. Attrition rates measured by the type of sponsoring institution range from 7.1% (academic health centers and medical schools) to 24.3% (vocational and technical schools). Programs sponsored by for-profit institutions and federal government-owned institutions report substantially higher attrition rates, 25.1% and 21.1%, respectively. PMID- 1870226 TI - Committee on Allied Health Education and Accreditation. Assessing educational outcomes and assuring quality. PMID- 1870227 TI - Medical competence and performance assessment. A new era. PMID- 1870228 TI - A study in post-Flexner survival. The Medical College of the State of South Carolina, 1913. AB - The Flexner report of 1910 resulted in the closing of many marginal medical schools and opened a new era in medical education in the United States. Caught in Abraham Flexner's net were several old schools with long histories and, as he said, "traditions and a certain present dignity" that lacked the minimum resources needed to meet the standards of the Council on Medical Education of the American Medical Association. One example was the Medical College of the State of South Carolina. It was consigned to oblivion in Flexner's plan, but survived. Dean Robert Wilson, MD, in his efforts to save his school, turned politician, enlisted the aid of the state's highly controversial governor, and initiated an effective lobbying campaign in the state legislature. The Council on Medical Education became involved unofficially in the person of its secretary, Nathan P. Colwell, MD. His presence in South Carolina was turned to advantage by Wilson and others and contributed substantially to the success of their efforts. PMID- 1870229 TI - US medical school finances. PMID- 1870230 TI - Medical education and financial assistance programs sponsored by US government agencies. PMID- 1870231 TI - Partnerships in medical education. PMID- 1870232 TI - Hospital-wide program identifies battered women; offers assistance. PMID- 1870233 TI - Tools available for health care providers whose patients are at risk for domestic violence. PMID- 1870234 TI - Duluth takes firm stance against domestic violence; mandates abuser arrest, education. PMID- 1870235 TI - From the National Institutes of Health. PMID- 1870236 TI - From the Centers for Disease Control. Multistate outbreak of Salmonella poona infections--United States and Canada, 1991. PMID- 1870237 TI - From the Centers for Disease Control. Use of folic acid for prevention of spina bifida and other neural tube defects--1983-1991. PMID- 1870238 TI - A piece of my mind. Soliloquy. PMID- 1870239 TI - Do Dna: alcoholism in the Soviet Union. PMID- 1870240 TI - Hippocracy. PMID- 1870241 TI - Opinion leaders vs audit feedback to implement practice guidelines. PMID- 1870242 TI - The epidemiologic necropsy for abdominal aortic aneurysm. PMID- 1870243 TI - Pseudotumor cerebri associated with danazol withdrawal. PMID- 1870244 TI - Financial threats to hospital libraries. PMID- 1870245 TI - Measles in New York City. PMID- 1870246 TI - Purpura due to inhaled quinidine. PMID- 1870247 TI - Long-term mortality after 5-year multifactorial primary prevention of cardiovascular diseases in middle-aged men. AB - OBJECTIVE: To investigate the long-term effects of multifactorial primary prevention of cardiovascular diseases (CVD). DESIGN: The 5-year randomized, controlled trial was performed between 1974 and 1980. The subjects and their risk factors were reevaluated in 1985. Posttrial mortality follow-up was continued up to December 31, 1989. SETTING: Institute of Occupational Health, Helsinki, Finland, and Second Department of Medicine, University of Helsinki. PARTICIPANTS: In all, 3490 business executives born during 1919 through 1934 participated in health checkups in the late 1960s. In 1974, 1222 of these men who were clinically healthy, but with CVD risk factors, were entered into the primary prevention trial; 612 were randomized to an intervention and 610 to a control group. INTERVENTIONS: During the 5-year trial, the subjects of the intervention group visited the investigators every fourth month. They were treated with intensive dietetic-hygienic measures and frequently with hypolipidemic (mainly clofibrate and/or probucol) and antihypertensive (mainly beta-blockers and/or diuretics) drugs. The control group was not treated by the investigators. MAIN OUTCOME MEASURES: Total mortality, cardiac mortality, mortality due to other causes. RESULTS: Total coronary heart disease risk was reduced by 46% in the intervention group as compared with the control group at end-trial. During 5 posttrial years, the risk factor and medication differences were largely leveled off between the groups. Between 1974 and 1989 the total number of deaths was 67 in the intervention group and 46 in the control group (relative risk [RR], 1.45; 95% confidence interval [CI], 1.01 to 2.08; P = .048); there were 34 and 14 cardiac deaths (RR, 2.42; 95% CI, 1.31 to 4.46; P = .001), two and four deaths due to other CVD (not significant), 13 and 21 deaths due to cancer (RR, 0.62; 95% CI, 0.31 to 1.22; P = .15), and 13 and one deaths due to violence (RR, 13.0; 95% CI, 1.70 to 98.7; P = .002), respectively. Multiple logistic regression analysis of treatments in the intervention group did not explain the 15-year excess cardiac mortality. CONCLUSION: These unexpected results may not question multifactorial prevention as such but do support the need for research on the selection and interaction(s) of methods used in the primary prevention of cardiovascular diseases. PMID- 1870248 TI - The geographic spread and temporal increase of the Lyme disease epidemic. AB - OBJECTIVE: To describe the temporal and geographic progression of the Lyme disease epidemic in New York State from 1977 through 1989. DESIGN: Communicable disease surveillance system. SETTING: Statewide. MAIN OUTCOME MEASURES: The progression of the epidemic was examined by analyzing trends in Lyme disease cases reported to the state surveillance system, town and county Lyme disease incidence rates, Lyme disease hospital discharge rates, and the distribution of Ixodes dammini ticks obtained from surveillance efforts and submitted for identification. MAIN RESULTS: The number of confirmed Lyme disease cases in New York has increased with concurrent increases in the number of hospital discharges. The number of counties endemic for Lyme disease increased from four to eight between 1985 and 1989. The number of counties with documented I dammini ticks increased from four in 1985 to 22 in 1989. Incidence of the disease also increased within known endemic counties. CONCLUSIONS: Tick surveillance indicated that the range of I dammini has expanded annually into areas up to 384 km from the original known endemic areas of Long Island, NY, and Connecticut. Cumulative data from human surveillance resources document both temporal increases and geographic expansion of the Lyme disease epidemic in New York. PMID- 1870249 TI - Reducing HIV sexual risk behaviors among runaway adolescents. AB - OBJECTIVE: Reductions in runaways' sexual risk behaviors were evaluated in response to an intensive program to prevent human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). DESIGN: In a nonrandomized control trial, sexual risk behaviors among 78 runaways at one residential shelter who received up to 30 HIV/AIDS intervention sessions were compared with 67 runaways at a nonintervention shelter with sexual behaviors assessed at baseline and 3 and 6 months. SETTING: Runaways were recruited from the only two publicly funded shelters in New York, NY. PARTICIPANTS: The runaways were aged 11 to 18 years, 64% female, and predominantly black or Hispanic. INTERVENTION: The intervention addressed general knowledge about HIV/AIDS, coping skills, access to health care and other resources, and individual barriers to safer sex. MAIN OUTCOME MEASURES: Consistent condom use, a high-risk pattern of sexual behavior, and sexual abstinence over a 3-month time frame were assessed. MAIN RESULTS: As the number of intervention sessions increased, runaways' reports of consistent condom use increased significantly (at 3 months, unique R2 = .06, P less than .05; at 6 months, unique R2 = .09, P less than .05), and their reports of engaging in a high-risk pattern of sexual behavior decreased significantly (at 3 months, unique R2 = .03, P = .06; at 6 months, unique R2 = .04, P less than .05). Abstinence did not change. CONCLUSIONS: The demonstrated effectiveness of the intensive HIV/AIDS program highlights the importance of enlarging the scope of most current HIV/AIDS prevention programs. PMID- 1870250 TI - Role of early fluid resuscitation in pediatric septic shock. AB - OBJECTIVE: To examine the association of the volume of fluid administered at 1 and 6 hours after presentation, with survival and the occurrence of the adult respiratory distress syndrome, cardiogenic pulmonary edema, and persistent hypovolemia during the resuscitation of children with septic shock. SETTING AND PATIENTS: All pediatric patients with septic shock presenting to the emergency department over a 6-year period and having a pulmonary artery catheter inserted by 6 hours after presentation were identified. METHODS: Patients were analyzed together and in three groups based on fluid volume in the first hour: group 1, less than 20 mL/kg; group 2, 20 to 40 mL/kg; and group 3, more than 40 mL/kg. Adult respiratory distress syndrome was diagnosed by the presence of alveolar infiltrates, hypoxemia, and a pulmonary capillary wedge pressure of 15 mm Hg or less. Cardiogenic pulmonary edema was diagnosed similarly, except the pulmonary capillary wedge pressure was greater than 15 mm Hg. Hypovolemia was diagnosed by the presence of oliguria, hypotension, and a pulmonary capillary wedge pressure of 8 mm Hg or less 6 hours after presentation. RESULTS: We identified 34 patients (median age, 13.5 months). At 1 and 6 hours, respectively, group 1 (n = 14) received 11 +/- 6 and 71 +/- 29 mL/kg (mean +/- SD) of fluid; group 2 received 32 +/- 5 and 108 +/- 54 mL/kg of fluid; and group 3 received 69 +/- 19 and 117 +/- 29 mL/kg of fluid. Survival in group 3 (eight of nine patients) was significantly better than in group 1 (six of 14 patients) or group 2 (four of 11 patients). Adult respiratory distress syndrome developed in 11 patients (32%) and cardiogenic pulmonary edema developed in five patients (15%). Having adult respiratory distress syndrome was associated with increased mortality, but adult respiratory distress syndrome was not increased in any group. Similarly, cardiogenic pulmonary edema was not associated with the fluid volume received or with decreased survival. Hypovolemia occurred in six patients in group 1 and two patients in group 2; all eight subsequently died. CONCLUSION: Rapid fluid resuscitation in excess of 40 mL/kg in the first hour following emergency department presentation was associated with improved survival, decreased occurrence of persistent hypovolemia, and no increase in the risk of cardiogenic pulmonary edema or adult respiratory distress syndrome in this group of pediatric patients with septic shock. PMID- 1870251 TI - The National Library of Medicine. Evolution of a premier information center. AB - From a small collection of medical publications in the Surgeon General's Office in 1836, the National Library of Medicine has developed into the leading repository of medical information in the world. Despite strong opposition and impediments from certain quarters, involving considerable machinations and intrigue, the determination of interested medical leaders and sympathetic members of Congress triumphed in having this remarkable institution established on the campus of the National Institutes of Health, Bethesda, Md. As a participant in many of the negotiations preceding that decision, I have happily witnessed the transformation of the Library, long housed in cramped, makeshift quarters, to its present magnificent structures in the heart of our nation's foremost medical research center. Its prodigious collection of print, audiovisual, and electronic information; its imaginative research projects; its excellent outreach program; and its innovative services and products are indispensable to all practicing health professionals, scientists, and medical educators, as well as to journalists, government officials, and others. The ultimate beneficiary, of course, is the patient. PMID- 1870252 TI - National medical response to mass disasters in the United States. Are we prepared? AB - Preparing for a resuscitation response to mass disasters, such as major earthquakes or industrial disasters, requires revisions of present local, regional, and national disaster plans. These should include the following: (1) life-supporting first aid and basic rescue capability of the lay public; (2) advanced trauma life support and advanced (heavy) rescue capability brought quickly to the scene from local and surrounding (regional) emergency medical services systems; and (3) trauma hospitals sending medical resuscitation teams to, and receiving casualties from, the disaster scene for resuscitative surgery and definitive care. Local and regional everyday emergency medical services systems would respond first. The armed forces should help, at least for transport and security. We propose that the National Disaster Medical System replace its civil defense model with an emergency medical services model, designed to mobilize rapid support for local emergency medical services systems from regional, state, and national resources. Coordination should be by one federal agency, such as the Federal Emergency Management Agency, which, however, needs to focus more on resuscitation through physician input. PMID- 1870253 TI - Photocoagulation for diabetic retinopathy. Early Treatment Diabetic Retinopathy Study Research Group. PMID- 1870254 TI - Status of a national disaster medical response. PMID- 1870255 TI - The latest report from Finland. A lesson in expectations. PMID- 1870256 TI - Lyme disease. Tracking an epidemic. PMID- 1870257 TI - Research funding and the media. PMID- 1870258 TI - The irreplaceable gift. PMID- 1870259 TI - [Humoral regulation of stem cell proliferation]. AB - The central feature of hematopoiesis is life-long, stable cell renewal. This process is supported by hemopoietic stem cells which, in the steady state, appear to be dormant in cell cycling. The recruitment of the dormant stem cells into cell cycle may be promoted by such factors as interleukin (IL)-1, IL-6, granulocyte-colony stimulating factor (G-CSF), and newly discovered IL-11. The effects of IL-1 on stem cells may be indirect. Once the stem cells leave Go and begin proliferation, the subsequent process is characterized by continued proliferation and differentiation. Though several models of stem cell differentiation have been proposed, micromanipulation studies of individual progenitors suggest that the commitment of multipotential progenitors to single lineages is a stochastic process. The proliferation of early hemopoietic progenitors requires the presence of IL-3 and/or IL-4, and the intermediate process appears to be supported by granulocyte/macrophage-CSF (GM-CSF). Once the progenitors are committed to individual lineages, the subsequent maturation process appears to be supported by late-acting, lineage-specific factors such as erythropoietin (erythropoiesis), G-CSF (neutrophil production), and IL-5 (eosinophilopoiesis). Thus, hemopoietic proliferation appears to be regulated by a cascade of factors directed at different developmental stages. PMID- 1870260 TI - [Chromosome rearrangements in leukemia]. AB - Information on the presence of specific chromosomal structural abnormalities in certain tumors has been increasing. Although the tumor specific chromosomal abnormalities were deemed important, it was not until the chromosomal location of several oncogenes was determined that the real molecular significance became apparent. It now appears that many of the genes associated with animal tumors are located near specific translocations in human cancers. The specificity of chromosomal changes have not only been used diagnostically and prognostically, but also they present key information for the molecular analysis in determining the nature of the genes of human neoplasia. In recent years, great advances have been made in our understanding of the molecular structure of the specific chromosomal translocations in certain hematologic disorders. The present report will briefly describe chromosomal rearrangements and how oncogenes or cancer related genes involved can be affected. PMID- 1870261 TI - [Chemotherapy of malignant lymphoma, with special regard to non-Hodgkin's lymphomas]. AB - Non-Hodgkin's lymphomas was considered an incurable disease 20 years ago, but it is now possible to administered intensive combination chemotherapy thanks to the development of new anticancer agents and the sophistication of their administration, making it possible to increase both the complete response rate and the 2-year survival rate to more than 80%. The outcome is that more than 50% of cases are now curable. One significant feature of non-Hodgkin's lymphoma in Japan is the fact that the prevalence of T-cell lymphomas, which is unfavorable, is higher than in Western nations. A check of the survival time of non-Hodgkin's lymphomas between the five years ending in 1970 and those beginning in 1971 indicates that it was significantly extended. In cases to which BACOP, HOP and other agents were concurrently administered during the initial course of treatment, the complete response rate increased over 70%, and the median survival time at 45 months, making it possible to hopes on the future development of chemotherapy. PMID- 1870262 TI - [Intimal injury and thrombus formation]. AB - One of the most important factor of thrombosis is intimal injury. We examined the morphology of thrombogenesis in the large artery using the rabbit as an experimental animal. When the intima was injured by a balloon catheter, we observed the adhesion of platelets onto the denuded area of the intima with various degrees of aggregation. Fibrinogen, fibronectin and vWF were observed on the surface of the aggregated platelets. In the raised thrombi induced by a polyethylene tubing fibrin thread formation was observed among the aggregated platelets. In the injured site showing interruption of internal elastic lamina by polyethylene tubing or wire tubing prominent fibrin formation was observed. The intima showing fibrous thickening which was induced by polyethylene tubing 3 weeks before the second injury also revealed prominent fibrin formation after the second injury. These thickened intima is considered to have an availability of a large amount of tissue factor for the activation of coagulation system than the normal intima. PMID- 1870263 TI - [Domain structure of human von Willebrand factor, and its modulators involved in the platelet adhesion process in vitro]. AB - von Willebrand factor (vWF), a macromolecular glycoprotein synthesized in endothelial cells and megakaryocytes circulates in blood as heterogenous multimers and plays a critical role in the formation of platelet plugs. vWF is composed of an identical subunit with a molecular weight (MW) of 270 kDa, which is held together by disulfide bonds. Functional domains of vWF for factor VIII, heparin, platelet glycoprotein (GP) Ib, collagen, and GP IIb/IIIa locate in this order from the N-to C-terminus of subunit. The GP Ib binding domain is cryptic in normal circulation and only becomes expressed when vWF is associated with the subendothelial matrix or with fibrin. In vitro, an antibiotic ristocetin or the snake venom botrocetin isolated from Bothrops jararaca mimics the active component of subendothelial matrix and causes the binding of vWF to GP Ib. To elucidate the mechanism of in vitro process of vWF-GPIb binding, we describe here the isolation and characterization of two distinct forms of botrocetin. Since ristocetin is a heavily glycosylated proteoid, it is hard to characterize the structure on the basis of amino acid analysis. The apparent MW of the one-chain botrocetin was 28 kDa before and 32 kDa after reduction of disulfide bonds, while that of the two-chain botrocetin was 27 kDa before and 15/14.5 kDa after reduction. Amino acid composition of the two species revealed a similar high content of potentially acidic residues (greater that 60 Asx and Glx residues/molecules) but significant differences in the content of Cys and Phe residues. The N-terminal sequence of the one-chain was Ile-Ile/Val-Ser-Pro-Pro Val-Cys-Gly-Asn-Glu-.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870264 TI - [Clinical and genetic aspects of antithrombin III deficiency and abnormal antithrombin III]. AB - Antithrombin III (AT III) has been confirmed to play an important role as a serine protease inhibitor in the mechanism of blood coagulation, and its deficiency or abnormality is found to cause thromboembolic disorders by reducing the anticoagulant activity. In this paper AT III gene of patient with congenital AT III deficiency, which was suggested to have qualitative abnormality by isoelectric focusing, was investigated. Analysis of the genomic structure by Southern blot hybridization with a cDNA probe (pAT6) revealed no detectable changes indicating any deletions, rearrangements and translocations. Therefore, we focused to analyze the sequence of exon 6 of AT III gene by polymerase chain reaction (PCR) methods followed by direct sequencing analysis. Nucleotide sequencing of exon 6 of AT III gene showed a G to T transitional mutation resulting in the conversion of arginine-406 to methionine coexisted with normal allele which encodes arginine. The mutation is located near the reactive center of AT III molecule, which region has been proved to be highly conserved during the evolution of serine protease inhibitor (serpin) family. From these results, it is concluded that the new type of mutation at amino acid site 407, which is similar to AT III Utah, is important for maintaining the structural and biological function of this inhibitor. PMID- 1870265 TI - [Type 1 plasminogen activator inhibitor: its role in biological reactions]. AB - The endothelial cells (ECs) are antithrombotic in the physiological states and maintains the integrity of blood circulation. However, ECs turn to be thrombotic upon being stimulated by various physiological mediators. These functions are mainly achieved by changing specific protein synthesis in ECs. Type 1 plasminogen activator inhibitor (PAI-1) is a serine protease inhibitor synthesized by ECs and thought to play a crucial role in the regulation of fibrinolysis. Basic research as well as clinical studies support this hypothesis. PAI-1 is a physiological inhibitor of both tissue-type plasminogen activator and urokinase-type plasminogen activator, key enzymes in the initiation of fibrinolysis. Thus PAI-1 regulates not only blood clot lysis but also a wide variety of biological reactions occurring in extracellular matrices such as tumor metastasis, neovascularization, inflammation, and cell migration. PAI-1 is a glycoprotein, of which molecular weight is approximately 50,000. Molecular biological analyses indicate that PAI-1 is synthesized as a single polypeptide composed of 402 amino acids containing a signal peptide. After post-translational modification, PAI-1 is secreted from ECs as a polypeptide composed of 379 amino acids and three N linked carbohydrates. PAI-1 lacks Cys residues, indicating that PAI-1 may not be rigid and thus thermolabile. In fact, PAI-1 is unstable even at 37 degrees C decaying into an inactive form with a biological half life of 2-3 hours. PAI-1 binds to a cell adhesion molecule, vitronectin. The association of PAI-1 with vitronectin appears to stabilize PAI-1. PAI-1 in complex with vitronectin is still accessible to plasminogen activators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870266 TI - [Production and secretion of the plasminogen activator inhibitor type-2 in a leukemia cell line]. AB - Differentiation-linked expression of plasminogen activator inhibitor-2 (PAI-2) was investigated by adding cell-differentiation promoting agents [such as phorbol myristate acetate (PMA), retinoic acid, dexamethasone (Dex), and recombinant cytokines, including tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta, granulocyte-colony stimulating factor, and interleukin-6 (IL-6)] into the culture medium of a promyelocytic leukemia cell line PL-21. PAI activity both in the culture medium and in the cell lysate increased approximately 70-fold after exposure to PMA. Both PAI-1 and PAI-2 antigens increased, but the amounts of the latter in the culture medium and in the cell lysate were approximately 10 times and 2,500 times, as much, respectively, as those of the former. Dex also increased the intracellular PAI activity approximately 6-fold, parallel with PAI 2 antigen. PAI-1 antigen increased only slightly in the culture medium but not in the cell lysate after Dex-stimulation. As with the case of PMA, TNF-alpha and IL 6 induced PL-21 cells to macrophage-like cells, but did not affect the PAI activity. Thus, the increase of the PAI-2 production by PMA may not necessarily depend on differentiation into macrophages. Other cytokines examined did not increase the PAI activity. PAI-2 antigen was demonstrated in the cell lysates of various leukemia cells by Western blotting technique using a monoclonal antibody against the PAI-2 purified from PL-21 culture medium. PAI-2 antigen was frequently detected in the plasmas from the patients whose peripheral leukocytes were more than 10,000/microliters. PMID- 1870267 TI - [Functional domains of von Willebrand factor]. PMID- 1870268 TI - [Treatment of 61 patients with acute myelogenous leukemia at first relapse]. AB - Treatment results in the 61 adult patients with AML in first relapse were analyzed to establish a better strategy for this group of patients. These patients received reinduction chemotherapy during 1979-1988. Complete remission (CR) was obtained in 57.4% of the cases, and the probability of survival and remaining in CR at five years was 11.9% and 17.9%, respectively. The longer duration of initial remission was favorable factor for achieving second CR. Type of reinduction regimens which were different from those used in the initial induction phase did not influence the second CR rate. The use of different consolidation regimen appeared to favorably affect the survival and probability of remaining in CR. PMID- 1870269 TI - [Influence of healthy human bone marrow fibroblasts on differentiation and proliferation of human leukemic cell line HL-60]. AB - The influence of bone marrow fibroblasts from healthy subjects on differentiation and clonal proliferation of HL-60 cells was studied. Clonal proliferation of HL 60 cells was examined by using agar culture method, DNA synthesis was done by counting 3H-thymidine incorporation into the cells, and differentiation of the cells was checked by non-specific esterase staining. The bone marrow fibroblasts and their conditioned-medium significantly stimulated colony formation and DNA synthesis of HL-60 cells, but they inhibited differentiation of the HL-60 cells. From these results, it was suggested that the bone marrow fibroblasts stimulated clonal proliferation of HL-60 cells and inhibited differentiation of the cells through humoral factors secreted by the fibroblasts. PMID- 1870270 TI - [Abnormal blood coagulation and fibrinolysis in chronic myeloproliferative disorders]. AB - Thirty-six patients with chronic myeloproliferative disorders (CMPD) were studied as regards blood coagulation and fibrinolysis. These studies revealed various mild abnormalities: activated thromboplastin time (APTT) tended to prolong and the level of factor V decreased significantly. In several cases, the levels of D dimer, thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex were elevated compared to normal. These results suggest that abnormal coagulation system in the patients with CMPD is related to low grade disseminated intravascular coagulation. Many coagulation factors did not correlate with peripheral blood cell counts. Two patients with polycythemia vera were evaluated for several abnormalities of the coagulation system before and during treatment. Coagulation abnormalities persisted after hematologic control had been achieved. Our results suggest that patients with CMPD have a chronic state of abnormal blood coagulation system even after normalization of blood cell counts. PMID- 1870271 TI - [Adult T cell lymphoma/leukemia with alopecia, huge tumors of scalp and wide destruction of cerebral bone]. AB - We reported rare manifestations of adult T cell lymphoma/leukemia. Patient was 41 year-old woman who has had progressive alopecia from childhood and developed multiple huge tumors (largest 10 x 15 cm) of scalp and wide destruction of cerebral bone at age of 39. A few abnormal lymphocytes (10%) appeared in the peripheral smear. Surface markers of peripheral lymphocytes showed two populations of CD4+/CD8- and CD4+/CD8+. HTLV-1 proviral DNA was demonstrated in the peripheral lymphocytes. Serum anti-ATLA antibodies was positive (X80). Biopsy of tumor revealed diffuse and large cell type of malignant lymphoma. Magnetic resonance imaging of head showed that tumors lysed the bone and invaded into cerebral regions. She was treated with CHOP regimen and irradiation, resulting of decreased tumor size and population of CD4+/CD8+. PMID- 1870272 TI - [Successful treatment of non-Hodgkin's lymphoma with consciousness disturbance due to hypercalcemia by the calcium-free hemodialysis and combined chemotherapy]. AB - A 63 year-old male, who was first diagnosed as primary macroglobulinemia (IgM kappa type) developed non-Hodgkin's lymphoma after 10 month clinical course. He had huge, multiple intrahepatic nodular lesions and had consciousness disturbance due to marked hypercalcemia. Since the treatment with gluco-corticoid and calcitonin was not effective for the improvement of patient's general condition, calcium-free hemodialysis was performed. After 2-hour dialysis, serum-Ca level was decreased from 15. 2mg/dl to 10.0mg/dl. Histology of the aspiration biopsy specimen obtained from the liver showed malignant lymphoma, diffuse, large cell type (B cell origin). Combined chemotherapy (CHOP) was started and was quite effective not only for the regression of the primary lesions but also for the normalization of the serum-Ca level. The existence of PTH-like substance produced by the tumor cell was suspected and may be related to the hypercalcemia in this case. Finally, our results demonstrated that calcium-free hemodialysis is safe and highly effective for the management of hypercalcemia caused by malignancy. PMID- 1870273 TI - [Chronic lymphocytic leukemia with bilateral exophthalmos and visual disturbance]. AB - A 61-year-old male was admitted to our hospital because of progressive bilateral exophthalmos and visual disturbance. He was diagnosed as chronic lymphocytic leukemia (CLL) with stage I of Rai system. Ophthalmologic examinations suggested that CLL cells might have invaded diffusely to bilateral orbits. Radiation to orbital lesions might result in other ophthalmologic complications such as cataract, therefore we tried to treat him with chemotherapy alone. As a result, combination chemotherapy consisting of vincristine, cyclophosphamide, prednisolone and doxorubicin (VEPA) and additional daily oral administration of cyclophosphamide were effective enough for his ophthalmologic recovery. PMID- 1870274 TI - [Diagnosis and treatment of Parkinson's disease in the elderly]. AB - The 159 patients with Parkinson's disease with onset after the age of 50 (mean: 62.3 years) were studied with reference to diagnosis and treatment. The results were as follows: 1. Other than the characteristic features, the symptoms at onset were depression (6% of the patients), lumbago (4%), hemiplegia-like (4%) and dizziness (3%), causing misdiagnoses in some of the patients. Among 159 patients studied, the severity most frequent was Yahr stage 3 (63%) at first examination, indicating the necessity of earlier diagnosis. 2. Magnetic resonance imaging (MRI) of the substantia nigra and striatum was investigated using a 1.5 Tesla field and T2-weighted images, which gave no specific results concerning diagnosis and severity. However, it was useful in differential diagnosis between this disease and parkinsonism caused by multiple system atrophy and cerebrovascular diseases. 3. With 123I-IMP SPECT, decrease in blood flow in the frontal and temporal lobes correlated with the severity (Yahr stage) of the disease. Regarding cognitive functions the scores of Hasegawa's Dementia Scale and Mini Mental State showed a highly significant correlation with the amount of blood flow in frontal and parietal lobes, suggesting that dementia might be caused by dysfunction of these lobes. 4. In 98 patients treated with levodopa mixed with dopa-economizers for more than a year, the maximum improvement was small in severely disabled patients of Yahr stage 5 and 4 because none improved to stage 3A or below (3A is an arbitrary criterion meaning mild involvement in stage 3 with 3P meaning more severe cases).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870275 TI - [Aging and graves' disease]. PMID- 1870276 TI - [Aging and diabetes mellitus]. PMID- 1870277 TI - [Antithrombotic therapy in geriatrics]. PMID- 1870278 TI - [Clinical and pathological study of cerebrovascular disease in the 60-101 age group]. AB - The purpose of this study is to clarify the clinical and pathological characteristics of cerebrovascular disease in nonagenarians and centenarians. In all autopsied cases from 1981 to 1986 (60-101 years old, 138 men and 157 women), cerebrovascular disease was observed in 32 cases (90-101 years old, 8 men and 24 women) and 174 cases (60-89 years old, 95 men and 79 women) in our hospital. The incidence of cerebrovascular disease was 58.3%, 68.8%, 75.1% and 64%, pathologically, in their sixties (60's), seventies (70's), eighties (80's) and over nineties (90's) respectively. In those who had cerebrovascular disease, cerebral infarctions were found in 79.9% of the cases of the under-90 group and 81.2% of cases of the over-90 group. In both groups, infarction was mainly found in over 2 regions, in the putamen, caudate, thalamus and in the white matter and cortex of the frontal lobe. In the over-90 group, the medium-sized infarctions decreased and small-sized infarctions increased. Cerebral hemorrhages were found in 16.1% of cases in the under-90 group and 12.6% of cases in the over-90 group. In the over-90 group, large-sized hemorrhages were found in 75%, and the incidence of hemorrhages was 50%, 50% in the lentiform nucleus and the subcortex respectively. The frequency of mental symptoms, frontal signs and oral dyskinesia in the over-90 group was significantly higher than in the under-90 group. The onset of cerebrovascular attacks was unknown in 43.8% cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870279 TI - [Age-related changes in clinical and prognostic significance of exercise-induced angina]. AB - Exercise-induced angina (EA) is an important manifestation of myocardial ischemia in stress testing. However, whether or not the presence of EA indicates a greater severity and worse prognosis of coronary artery disease is uncertain. It is well known that the elderly have a greater prevalence of silent myocardial infarction. This suggests that the incidence and significance of EA in elderly patients may differ from those in the younger patients. Therefore, we, at first, studied the age-related change in the incidence of EA by reviewing 983 consecutive treadmill tests. Furthermore, to evaluate the age-related change of the clinical and prognostic significance of EA, exercise tests, angiographic findings and 29 months follow-up data were assessed in 142 patients without prior myocardial infarction who underwent treadmill test and coronary angiography (CAG) for the investigation of coronary artery disease. The rate of positive test results among 983 treadmill tests exceeded 30% only in patients 60 years old or older. Accordingly, we divided the patients into two different age groups: middle-aged patients (less than or equal to 59 yr, M-patients) and elderly patients (greater than or equal to 60 yr, O-patients). Among 983 treadmill tests, O-patients had a higher rate of positive results (presence of EA or positive ECG criteria) than M patients (36 vs. 24%, p less than 0.001). However, incidence of EA was similar in the 2 groups (17 vs. 14%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870280 TI - [Crossed cerebellar atrophy following cerebrovascular lesions]. AB - A neuroradiological study of crossed cerebellar atrophy (CCA) was performed using X-ray CT in 103 patients suffering from unilateral supratentorial cerebrovascular diseases. CCA was demonstrated in 9 (8.7%) of 103 patients. No difference between the occurrence of CCA in cerebral hemorrhage and that in cerebral infarction was found. CCA was seen in the chronic stage of cerebrovascular disease more than 3 years since stroke occurrence, and was found to be present more frequently and to a greater extent 7 years later. No correlation between the site of bleeding and the occurrence of CCA was found. Trans-synaptic degeneration of the corticopontocerebellar tract was considered in CCA following putaminal and combined hemorrhage involving an internal capsule lesion. However, in thalamic hemorrhage, retrograde degeneration within the cerebellorubrothalamic tract was presumed. CCA following cerebral infarction was seen in patients with massive lesions in the territory of the middle cerebral artery. Multivariate analysis showed that lesions of the parietal and frontal lobes appeared to greatly contribute to the development of CCA. As the degeneration and atrophy in the thalamus on the side of the lesion appeared early and frequently, it was suggested that retrograde degeneration of the cerebellorubrothalamic tract participated, in addition to anterograde corticopontocerebellar tract degeneration, in CCA following middle cerebral artery infarction. It is likely that CCA is caused by both transsynaptic degeneration of the corticopontocerebellar tract and the cerebellorubrothalamic tract. PMID- 1870281 TI - [Frequency of complications of mitral valve prolapse in the elderly]. AB - To evaluate the difference in the frequency of complication of mitral valve prolapse (MVP) according to sex in subjects aged 60 years and older, 543 patients (218 men and 325 women) who were diagnosed as having MVP by echocardiography at the Lahey Clinic Medical Center were studied. Three hundred and fourty eight patients had no complication of MVP (male vs female = 129:219). Infective endocarditis occurred in 20 patients (male vs female = 13:7). Rupture of chordae tendineae occurred spontaneously in 29 patients (male vs female = 20:9) and were associated with infective endocarditis in 8 other patients (male vs female = 6:2). Eighteen patients required mitral valve surgery for severe mitral regurgitation. The frequencies of these complications were higher in males than those in females. Cerebral ischemic events were encountered in 54 patients. There was no significant difference in the frequency between male and female. In conclusion, MVP in elderly men might be at for cardiac complication. PMID- 1870282 TI - [Daily activity evaluated from total energy consumption in the chronic stage of myocardial infarction and limiting factors in elder patients]. AB - In chronic case of myocardial infarction (OMI), alternation of a daily total energy consumption (DTEC) between in OMI and in the pre-infarction stage was investigated. The limiting factors of DTEC, including functional classification according to New York Heart Association (NYHA) subset, Forrester's hemodynamic subset (FS) in the stage of acute myocardial infarction (AMI), numbers of significant coronary arterial stenosis (NCAG), cardiac function at rest in OMI, for example; cardiac index (CI), pulmonary capillary wedge pressure (PCW), left ventricle end-diastolic pressure (EDP) and exercise tolerance in OMI, were considered. Subjects, consisting of 191 OMI cases, were classified into the younger group less than 59 years old (79 males and 10 females) and the older group greater than 60 years old (102 males and 23 females). Daily physical activity was examined by questionnaires from these patients and DTEC was calculated based on daily physical activity. Results in the younger group and older group were investigated separately. Reduction of DTEC after myocardial infarction was recognized in all ages and both sexes, however, reduction of DTEC in the older group was less than in the younger group, especially in males. Concerning the limiting factors of the older group, exercise tolerance in OMI was related to reduction of DTEC. NYHA category, FS in the AMI stage, NCAG, CI, PCW and EDP had no significant relation to DTEC. In addition, the effects of social limiting factors, for instance retirement, and mental limiting factors were considered to be important. PMID- 1870283 TI - [Computer-aided visuospatial cognitive-performance test]. AB - The validity of a newly developed computer-aided "Visuospatial Cognitive Performance Test" (VCP-Test) was examined in two populations, 68 normal elderly volunteers (mean age, 69.5% years) and 25 patients with dementia (mean age, 68.2 years). None of the cases in the two groups had either motor impairment or ataxia. The VCP-Test was a kind of vigilance task in which a subject is required to tap the key corresponding to the local change-over of the image on the computer display as quickly as possible. After 40 trials, consecutive data of performance efficiency were automatically displayed on the LCD display and printed out. A significant negative correlation between the VCP-Test and age in normal elderly population was recognized. Moreover, the relationship between the VCP-Test and the Hasegawa Dementia Scale (HDS), and the Mini-Mental State (MMS) was also significant in patients with dementia. In conclusion, the VCP-Test was considered to be useful for geriatric neurobehavioral functional assessment and for the detection of dementia. PMID- 1870284 TI - [Cholesterol, atherosclerosis and cerebro-cardiovascular complications in 3,236 elderly autopsy cases]. AB - The effect of serum cholesterol on aortic, cerebral, coronary and femoral atherosclerosis as well as on the incidence of cerebral and myocardial infarctions were analyzed in 3,236 consecutive autopsies in the elderly. Serum cholesterol levels declined over the age of 80 in both genders. The cholesterol levels of females were significantly higher than that of males in each age group from the sixties through the nineties. The increase in serum cholesterol was correlated with the progression of coronary atherosclerosis in both genders, but not with cerebral or femoral atherosclerosis. Slight progression of aortic atherosclerosis was observed when serum cholesterol was over 160 mg/dl. Cholesterol induced progression of coronary atherosclerosis was found in cases with hypertension, but not in the normotensive group. In accordance with the progression of coronary atherosclerosis, the incidence of myocardial infarction increased with an elevation of serum cholesterol levels, and this relationship between myocardial infarction and cholesterol levels was found only in patients with hypertension. No correlation was found between the incidence of cerebral infarction and serum cholesterol levels. It was concluded that hypercholesterolemia in the elderly is a risk factor of myocardial infarction in cases with hypertension, but is not a risk factor of cerebral infarction. PMID- 1870285 TI - [Noninvasive evaluation of arteriosclerotic changes in patients with diabetes mellitus]. AB - In order to evaluate atherosclerotic changes in diabetes mellitus (DM), pulse wave velocity (PWV), forearm blood flow (FBF: by venous occlusion strain gauge plethysmography), forearm vascular resistance (VR: mean arterial pressure/FBF) and radial artery blood velocity (RABV: by ultrasonic Doppler) were determined noninvasively in healthy controls (n = 15) as well as age-matched diabetic patients with (DMHT, n = 11) or without hypertension (DMNT, n = 21). Both in controls and diabetic subjects, PWV demonstrated a significant positive correlation with age. Diabetics tended to show higher, although not significantly higher, PWV in comparison with controls. In controls, but not in diabetics, FBF and VR respectively demonstrated a significant negative and positive relationship with age. Diabetics younger than 50 years had a lower FBF and a higher VR in comparison with age-matched controls. In the DMHT group, FBF was significantly attenuated. There was no difference in RABV between controls and diabetic group. PWV did not correlate with FBF or VR. However, FBF did show a significant negative correlation with VR. RABV negatively correlated with FBF in diabetics, indicating that FBF may reflect distensibility in forearm arteries and veins. These results suggest that FBF may be a better arteriosclerotic index for resistance vessels and DM or hypertension may accelerate arteriosclerotic changes. PMID- 1870286 TI - [The relationship between the aortic pulse wave velocity and osteoporosis in elderly women]. AB - The relationship between arteriosclerosis and osteoporosis (OP) was assessed in 20 elderly women. The aortic pulse wave velocity (PWV) was used as the index of arteriosclerosis and bone mineral content (BM) of the vertebral body, which was measured by quantitative computed tomography, was used as an index of OP. PWV and BM showed a significant correlation with aging (PWV and age: r = 0.466, p less than 0.05, BM and age: r = -0.487, p less than 0.05). In the group in which the serum alkaline phosphatase (ALP) was higher than 180 IU/l (n = 11), there was a significant inverse correlation between PWV and BM (r = -0.728, p less than 0.02). On the other hand, there was no correlation between PWV and BM in the group in which ALP was lower than 180 IU/l (n = 9). These results suggest that in cases with OP and high levels of ALP, calcium (Ca) seems to be released from the bone system and transferred to the wall of the aorta. The mechanism and pathogenesis of this Ca transference is unknown and should be investigated. PMID- 1870287 TI - [Morphological changes accompanying compensatory lung growth after pneumonectomy in rats]. AB - To elucidate morphological change of alveoli in compensatory lung growth, left pneumonectomy was performed on male 4 weeks-old rats (Fischer-344) and light microscopic morphometry, scanning electron microscopic study and histochemistry using anti-bromodeoxyuridine were made. The wet lung weight and lung volume of the residual lungs in the pneumonectomized rats reached the same as those of sham operated rats at one and two weeks after the operation, respectively. From the data concerning the mean linear intercept in the cardiac lobe of the pneumonectomized rats, alveoli of two different sizes were observed, suggesting that the compensatory lung growth in the alveoli may take two steps or at least two different sizes of alveoli may exist mixed together. The data of histochemistry suggest that in pneumonectomized rats the alveoli beneath the pleura (less than 2 mm) included an increased number of S phase cells compared with those of deeper areas. From these morphological changes in the lungs of the pneumonectomized rats it is possible to suggest a hypothesis that stretch stimulation is the first trigger in compensatory lung growth. PMID- 1870288 TI - [Changes of muscarinic cholinergic binding by human lymphocytes with normal aging and Alzheimer's disease]. AB - A potent, new muscarinic cholinergic antagonist, L-[N-methyl-3H] quinuclidinyl benzilate methyl chloride ([3H-]-NM-QNB) was used to detect functional changes of muscarinic acetylcholine receptors (mAChR) on human lymphocytes in relation to age. Using techniques developed for the study of mAChR in brain homogenate, direct binding to whole live lymphocytes was shown for [3H]-NM-QNB. We examined Group of healthy adult females (41-66 years old, N = 34) and patients with "probable" Alzheimer's disease (55-75 years old, N = 11). It was shown that mAChR on lymphocytes were divided into two subtypes; high affinity (Ms) and low affinity types (Mw) for a ligand, [3H]-NM-QNB. For the healthy controls (age range 41-66 years old, N = 31), a negative correlation (r = -0.172) was found between Kd (Ms) and age. Also the negative correlation between Bmax (Ms) and age was shown to be weak (r = -0.164). The regression equations are: Y = 11.9X + 1306.4 (Kd(Ms); N = 31) Y = -80.6X + 8296.1 (Bmax(Ms); N = 31) where, X and Y designate the age of individuals and Kd (or Bmax), respectively. Hence, for patients with Alzheimer's disease, no significant changes with age in Kd (Ms) or Bmax (Ms) were obtained. Furthermore, correlations between the stage of clinical dementia of patients and Kd (Ms), and between the staging and Bmax (Ms) were shown to be strong (p less than 0.05). Significant change (p less than 0.05) in Bmax (Ms) was recognized in lymphocytes from patients with Alzheimer's disease (N = 11), compared with age-matched controls (N = 20).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870289 TI - [An autopsy case of progressive supranuclear palsy with central pontine myelinolysis]. AB - An autopsy case of progressive supranuclear palsy (PSP) associated with central pontine myelinolysis (CPM) is reported. A 73-year-old male patient suffered from gait disturbance for about 5 years. The clinical features were characterized by gradual development of supranuclear ophthalmoplegia, tremor, bradykinesia, rigidity, neck dystonia, dementia and pseudobulbar palsy at the advanced stage of his illness. Treatment with levodopa did not improve his neurological signs and symptoms. PSP or multiple system atrophy was considered as a clinical diagnosis of the patient. He died of pneumonia, acute pancreatitis and liver dysfunction in November 1985. The main neuropathological findings were neuronal loss and gliosis with neurofibrillary tangles of globose type in the globus pallidus, subthalamic nucleus, substantia nigra and dentate nucleus, and at the base of the pons, bilateral and symmetrical demyelination was found. In addition, myelin staining revealed circumscribed pallor in the cerebral white matter. The histologic diagnosis was PSP associated with CPM. An association of PSP with CPM is rare in the elderly and possible etiologic factors of both diseases were discussed. PMID- 1870290 TI - [Gentamicin kinetics in the blood and aqueous humor of the rabbit eye after intramuscular and subconjunctival administration]. AB - Investigations were performed in rabbits which were given gentamycin intramuscularly and subconjunctivally. After subconjunctival application gentamycin passes quickly into the eye and its therapeutical level persists up to 1 hour. After intramuscular injection gentamycin is passing slower into the aqueous but persists there longer (the therapeutical level--up to 5.5 hours). PMID- 1870291 TI - [Optic nerve microcirculation. III. Lamina cribrosa]. AB - The architecture of the lamina cribrosa was investigated on the material of 160 optic nerves of people decreased at the age of 6 months to 80 years, free of pathological changes of circulation. The posterior segment of lamina cribrosa is supplied by arterial blood from: centripetal arterioles of the pia mater, ramifications from the secondary and tertiary posterior short ciliary arteries and from the longitudinal net of capillaries of the optic nerve. The central part of the lamina cribrosa is supplied by the twigs of the complete or incomplete vascular ring of Zinn-Haller or directly from secondary twigs of choroidal arteries. The anterior part of lamina cribrosa is vascularized by choroidal vessels and in a minor part by the vascular ring of Zinn-Haller. The circulation in the area of lamina cribrosa is integrally connected with the system of posterior short ciliary arteries and the arterioles of the internal vagina of the optic nerve. The central retinal artery does not give up any branches in this region. Similarly to other segments of the optic nerve there exists an individual variability in the system and course of the vessels in the lamina cribrosa. The vascular system of lamina cribrosa is connected anteriorly with the vessels of the paralaminar area of the optic disc which receive vascular branches from early ramifications of the central retinal artery (25 p.c. of cases). PMID- 1870292 TI - [Effect of noise on ocular accommodation]. AB - The goal of investigations was the determination of connection between the level of noise and the extra-auditory reaction of the organism--a change of the near point. Changes of accommodation determined by means of a black-and-white check board test were monitored in the course and after 1 hour exposition to noise of 90 dB-A, 93 dB-A, 96 dB-A or 99 dB-A of the sound level. The results show that the deterioration of vision is a complicated exponential function of the intensity and time of the exposition to noise. PMID- 1870293 TI - [Corneal endothelial proliferation in anterior synechiae: experimental and clinico-histopathological studies]. AB - Corneal endothelial proliferation over the iris was studied on experimental anterior synechiae in rabbits up to 6 months. Clinico-pathologic studies of 102 post-keratoplasty eyes revealed that only 4 out of 51 anterior synechiae were endothelialized. In contrast all 10 leukomatous+ adhesions found in a series of 132 eyes removed after perforating corneal trauma were endothelialized. The above studies suggest that the most important factor for endothelial proliferation is the availability of suitable substrate. The rate of growth depends on growth factors present in anterior chamber. PMID- 1870294 TI - [Pathogenesis of secondary glaucoma in epithelial invasion]. AB - Apart from meticulous wound closure certain amount of fibrin and fibroblastic activity are necessary to prevent epithelial ingrowth. Prostaglandin inhibitors and steroid may enhance such danger. The most frequent reason for glaucoma were peripheral anterior synechiae. Open angle glaucoma with stratified epithelium lining the trabeculum was less frequent. Glaucoma can be caused by goblet cells produced mucus blocking the trabeculum. Desquamated epithelial cells, pupillary block caused by epithelial invasion of anterior hyaloid and intense inflammatory reaction can also exceptionally induce secondary glaucoma. PMID- 1870296 TI - [Examination of the visual system in boxers]. AB - Ophthalmological examinations were performed in 139 boxers. They showed that the injuries concerned most frequently the ocular adnexa and not the eye globe itself. Only two contestants who practiced boxing for more than 10 years exhibited peripheral opacities of the lens and pale foci with shifting of the pigment at the fundus periphery connected with a deepening of the filtration angle; this could be caused by a contusion of the eye. It was demonstrated that the introduction of safety helmets distinctly reduced the number of eye injuries in boxing. PMID- 1870295 TI - [Eye tumors in children. Histopathological aspects of differential diagnosis]. AB - Ocular tumors in children, due to their biological characteristics, possess a special position in ophthalmology. Most of these tumors are today curable with early diagnosis and correct treatment. Therefore their differential diagnosis should be familiar to all pediatricians and ophthalmologists. Tumors were divided into three groups, concerning their localization (lid and orbit, epibulbar, intraocular). In each group histopathologic and clinical pictures of most important benign (hamartomas, choristomas and pseudotumors) and malignant (primary and metastatic) tumors were separately described and correlated, with special attention paid to differential diagnosis. PMID- 1870297 TI - [Problems of intraocular pressure and the early period of primary open-angle glaucoma]. AB - The author presents the up-to-date opinions on the problem of "normal" intraocular pressure connecting it with another hydro- and haemodynamic parameters of the eye. Subsequently he discusses the contradictory opinions whether one has to distinguish two clinical conditions: intraocular hypertension and the initial period of open angle glaucoma. According to the author the initiation of the ++anti-glaucoma treatment should be considered individually in each particular case but before the onset of changes at the fundus and before the impairment of the visual field. PMID- 1870298 TI - [Liposomes containing dexamethasone-- ophthalmic ointment]. AB - Presented is the method of production of the liposomal form of dexamethasone. The liposomes have been obtained by the method of manual shaking out. Dexamethasone contained in liposomes MLV was connected with a base forming a 0.05% ophthalmic ointment. The drug prepared in this manner was used in an experimental viral interstitial keratitis in rabbits. PMID- 1870299 TI - [10-year experience with the health resort treatment of eye diseases]. AB - Presented are the kinds of ocular diseases which can be qualified for a health resort therapy and the kinds of measures the most beneficial in particular cases. After the cure an improvement in the condition of the eyes was found in 68 p.c. of cases. On the basis of results one may conclude that the rehabilitating health resort treatment is worth to be suggested. PMID- 1870300 TI - [Observation or enucleation--a still unsolved problem in patients with uveal melanoma]. AB - The authors performed retrospective investigations and evaluated the influence of the period of time between the onset of the first symptoms of the disease and the enucleation on the life expectations; the groups of patients treated by enucleation and non-treated were compared. Various opinions on the influence of enucleation on the prognosis in patients with uveal melanoma were discussed. PMID- 1870302 TI - [Anterior chamber lenses--the Pannu and other models]. AB - Presented was the comparison of early and late complications arising after implantation of the anterior chamber lenses of the type Kelman Omnifit and Pannu. The period of postoperative observations amounted 1-3 years. It was demonstrated that the Pannu lenses are giving less complications; the authors are connecting this fact with an easier operative technique of their implantation and their greater ability of autoadaptation. PMID- 1870301 TI - [Effect of X-ray irradiation of the orbit after enucleation in patients with uveal melanoma]. AB - Retrospective investigations comprising 154 patients with an uveal melanoma treated in the period of 1945-1984 were performed. Evaluation of the methods applied showed a beneficial effect of combining enucleation with a postoperative irradiation of the orbit. PMID- 1870303 TI - [Simultaneous extracapsular cataract extraction with trabeculectomy after uveitis]. AB - Simultaneous cataract extraction and anti-glaucoma operation was performed in 11 patients (16 eyes) who suffered uveitis. In all the cases extracapsular extraction and double trabeculectomy were performed according to personal modifications. The cataract was extracted by extracapsular method and subsequently the trabeculectomy was executed at 11 and 1 o'clock. Normalization of the IOP was attained in 13 eyes, 3 eyes needed application of Timolol. The results encourage to further use of this procedure. PMID- 1870304 TI - [Anterior vitrectomy in the treatment of post-traumatic defects of the eye]. AB - The authors analyse the results of 116 operations in which they performed anterior vitrectomy using the Berkeley's and Opticon vitrectomes. Operations of this type have been performed in cases of traumatic cataract, subluxated and luxated lenses. One removed also post-inflammatory membranes and the vitreous from the anterior chamber and from the area of the wound. The functional and anatomical results have to be acknowledged as satisfactory. PMID- 1870306 TI - [Use of Nd-YAG laser in capsulotomy]. PMID- 1870305 TI - [Nd-YAG laser in the treatment of various forms of secondary cataract]. AB - Described is the method of secondary cataract extraction by means of a Nd-YAG laser; the results obtained in 34 patients (12 adults and 22 children) are presented. Intraoperative complications--anterior chamber haemorrhages and rise of the IOP among others--had a transitory character and did not influence the final result of treatment. PMID- 1870307 TI - [Pathological changes found in the lacrimal sac during nasolacrimal duct surgery]. AB - In the course of 489 external dacryocystorhinostomies one found: 19 pseudotumors (granulomas and inflammatory granulations), 6 true tumors (1 papilloma, 1 congenital cyst, 1 lymphoma), 6 cases of calcium deposits and stones and 1 case of epithelial metaplasia. The author points to a great number of pseudotumors which are the effect of a long-standing process of dacryocystitis treated conservatively without effect. She thinks that the surgical treatment should be undertaken as fast as possible. PMID- 1870308 TI - [Ultrastructure of the lacrimal film and the "dry eye" syndrome]. PMID- 1870309 TI - [Polish contribution to the electrophysiological studies in ophthalmology. I. Technology and animal studies]. AB - The methods of investigations by means of electroretinography, electrooculography, electronystagmography and electromyography and the use of visual evoked potentials are presented. Described are experimental investigations and the obtained results in animals (frogs, rabbits and vietnamese pigs) by several Polish research workers and contained in ca. 120 works published in the period 1960-1986. PMID- 1870310 TI - [Polish contribution to the electrophysiological studies in ophthalmology. II. Clinical studies--early detection of disorders of the visual system]. AB - Presented are the results of Polish investigations in various ocular diseases: in retinal detachment, glaucoma, cataract, in disturbances of function of the ocular nerves and muscles and in fundus changes in general pathological conditions. Investigations have been carried out at the university centres of Warsaw, Wroclaw, Gdansk and Szczecin. PMID- 1870312 TI - [Medical problems of the automated control of astronauts' health]. AB - A typical structure of an automatic complex for dynamic medical monitoring of the health status of crewmembers in space is described. Algorithms of medical data processing and data imaging are discussed. Approaches to automatic diagnosis of functional states are presented. Advanced automatic systems related to medical support of future flights to Mars are described. PMID- 1870311 TI - [Status of water-electrolyte homeostasis and the systems of hormonal regulation during 237-day space flight]. AB - On mission days 216-219 two crewmembers collected urine and recorded their food and water consumption during three days on end. The cosmonaut-physician withdrew blood samples from the vein and finger. In addition, he made venipuncture to himself and drew blood. Urine and blood samples were frozen and returned to the ground for analysis. In spite of individual variations of each cosmonaut, they all showed a trend for water and sodium retention which was provided by adequate hormonal rearrangement, i. e. increased production of ADH and aldosterone. No disorders in calcium and phosphorus metabolism were seen. Immediately postflight the cosmonauts displayed typical changes in fluid-electrolyte balance and renal function that suggested body dehydration and adjustment to Earth's gravity. PMID- 1870313 TI - [The main trends in the development of the equipment for physiological studies on the Earth and in space]. AB - Recent advances in electronics and computers are widely used in present-day physiological equipment. Microprocessors are part of hardware complexes and nonstandard equipment. This increases significantly experimenter's capabilities in terms of experimental control and data processing and storage. These trends acquire great significance for the production of space-oriented research equipment in which automation of experimental control and data processing is highly important. Examples of experimental equipment for space physiology studies designed and developed through cooperative efforts of the USSR, socialist countries, NASA, ESA, and CERMA are considered. PMID- 1870314 TI - [Anthropo-ecological aspects of occupational health and various biochemical approaches to the problem of its evaluation in workers in high risk occupations]. AB - This paper presents the concept of occupational health of man, interpreted as the process of maintenance and development of regulatory properties of the body and his physical, psychic and social well-being, which provide high reliability of his professional activities, professional longevity and maximal lifetime. The paper discusses the main areas of biochemical investigations to evaluate occupational health of the flying personnel, which include identification of correlates between biochemical or immune changes and pathological or premorbid states, that reduce tolerance to environmental effects, as well as study of functional specificities related to the reserves and mechanisms of implementation of adaptive capabilities of the human body. It gives detailed biochemical data derived from pilots with neurotic problems and biochemical indicators of stress tolerance measured during exposure to +Gz acceleration, angular acceleration, hyperthermia, hypoxia, and exercise. PMID- 1870315 TI - [The role of cholinergic regulation and stabilization of myocardial structures in the adaptive protection of the heart]. AB - It was found that rat immobilization in small-size cages leb to physiological changes. On day 1 it was a stress-reaction that resulted in decreases of the fibrillation threshold and arrhythmia resistance. On day 5 it was an increase in the vagal tone that caused noticeable atropine-relieved bradycardia. The fibrillation level returned to the baseline. Heart resistance to ischemic and reperfusion arrhythmias increased drastically as compared to the control level. On day 15 the vagal effect declined to reach the baseline; in spite of this heart tolerance to reperfusion arrhythmias further increased. This was followed by enhanced resistance of isolated hearts of the adapted animals to the reperfusion paradox and tonic concentrations of epinephrine and Ca2+, which indicated the formation of the phenomenon of adaptation stabilization of cardiac structures. After termination of the 5-day stressogenic exposure the cholinergic stress limiting protection of the heart disappeared rapidly, i. e. within 12 hours. The protective effect of the adaptation stabilization phenomenon, which developed during 15 days of the stressogenic exposure, proved to be more stable and persisted during 15 days after its cessation. It is concluded that, based on the coordination of short-term central and long-term cellular mechanisms, the animal body develops optimal adaptation that emerges rapidly and persists for an adequately long period of time. The step-by-step replacement of central mechanisms with cellular ones provides high reliability and efficiency of the protection of the heart and the entire body from extended environmental effects. PMID- 1870317 TI - [Reaction of various components of the erythrocyte system to periodic action of submaximal loads]. AB - During repeated exposures of rats to hypergravity two stages of catabolic and adaptive developments in red blood were distinguished. The first stage that lasted about a week was characterized by decrease of resistance and hemolysis of red blood cells, hemosiderosis in the spleen, circulation hypoxia in the liver. The second stage was characterized by the predominance of adaptive processes, viz. increased activity of red blood cells, enhanced erythropoiesis in the spleen pulp, and appearance of highly active hepatocytes. PMID- 1870316 TI - [Contractile properties of skeletal muscles of rats after flight on "Kosmos 1887"]. AB - Contractile properties of skeletal muscles of rats were investigated using glycerinated muscle preparations that were obtained from Cosmos-1887 animals flown for 13 days (plus 2 days on the ground) and from rats that remained hypokinetic for 13 days on the ground. In the flow rats, the absolute mass of postural muscles remained unchanged while their relative mass increased; this may be attributed to their enhanced hydration which developed during the first 2 days after landing. Strength losses of the postural muscles were less significant than after previous flights. Comparison of the Cosmos-1887 and hypokinesia control data has shown that even 2-day exposure to 1 G after 13-day flight can modify drastically flight-induced changes. PMID- 1870319 TI - [Changes in serotonin and histamine levels in human blood after 370-day anti orthostatic hypokinesia]. AB - Ten healthy men took part in a 360-day antiorthostatic hypokinesia study. They were subdivided into two equal groups that differed in terms of time when they started using counter-measures: Group A began exercising on the first day of exposure and Group B on bed rest day 120. As compared to the baseline, the test subjects showed a decrease of serotonin (Ser) and histamine (HA). The only exception was HA increase on bed rest day 50 in the Group A subjects. The difference in Ser and HA concentrations in Group A and B subjects was insignificant on bed rest days 110 through 350. On the 60th day after the study Ser and HA concentrations did not yet return to norm. These observations indicate that changes in the serotonin- and histaminergic systems cannot be compensated within the above period of time. PMID- 1870318 TI - [Carbohydrate and lipid metabolites and blood serum enzymes in humans during graded exercise test in long-term anti-orthostatic hypokinesia]. AB - Exercise tests were carried out before as well as on days 128 and 248 of a 370 day head-down tilt study. The test subjects, who took part in the study, were divided into two groups that used different regimens of countermeasures (drugs and exercise). During exercise tests the following serum parameters were measured: lactate, pyruvate, glucose, triglycerides, nonesterified fatty acids, lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, malate dehydrogenase, creatine phosphokinase. Decrease or delayed increase in the concentration of energy substrates (nonesterified fatty acids and triglycerides) after a standard exercise test is a metabolic manifestation of deconditioning changes induced by head-down tilting. Insufficient supply of a working human body with readily utilizable lipid substrates causes inadequate activation of energy forming enzymes and excessive buildup of metabolites, i. e. lactate and pyruvate. The efficacy of corrective and prophylactic measures was verified by biochemical data. PMID- 1870320 TI - [Experimental device for evaluation of physical endurance of animals]. PMID- 1870321 TI - [Dynamics of hematocrit values in humans during space flights of varying duration]. PMID- 1870324 TI - 30th annual scientific meeting of the Biological Engineering Society. Durham, 18 20 September 1990. PMID- 1870322 TI - [Effect of hypokinesia on food consumption and muscular atrophy of the extremities in rats: effect of insulin]. PMID- 1870323 TI - [Effectiveness of laser acupuncture in the preservation of the structure of the skeletal muscles during long-term hypokinesia]. PMID- 1870325 TI - Soft layered prostheses for arthritic hip joints: a study of materials degradation. AB - A great deal of interest is being shown in complaint bearing surfaces for artificial joints. These produce very low friction because of the fluid-film lubrication that they exhibit, and therefore should produce lower wear than current prosthetic materials as the two surfaces of the joint are completely separated by a film of synovial fluid. However, one problem with soft elastic materials in vivo is that the elastomers may degrade with time. Specimens of four polyurethanes were kept in Ringer's solution at 37 degrees C for about 4 months to investigate changes in mechanical properties and the mode of lubrication with time of immersion. The materials tested were a polyether-urethane (E57), a polyester-urethane (E58), an aromatic polyether-urethane (P1) and an aliphatic polyether-urethane (A1). Samples of E57 showed a decrease in hardness and elastic modulus of 21% and 28% respectively. This was much better than E58 which showed decreases of 32% and 42% respectively. Better results were achieved with A1 (hardness change 2%) and P1 (decrease in hardness of 14% and modulus 17%). When tested in a hip-function simulator, A1 showed virtually no change in its very low coefficient of friction (0.004), P1 showed an increase of 60%, while E57 and and E58 both showed a doubling in friction over the course of the study. The modes of in vitro degradation were considered and surface effects determined to be most damaging. Currently the best candidate for a compliant material in hip replacement is the aliphatic polyether-urethane which maintains fluid-film lubrication. PMID- 1870327 TI - A laser Doppler scanner for imaging blood flow in skin. AB - This paper describes a novel medical instrument that produces an image of blood flow in the capillaries under the skin surface. A laser beam is used to detect blood cell motion from the Doppler broadening of the laser light scattered from the skin. The image is generated by scanning the laser beam in a raster. The design of a practical clinical instrument is outlined and some preliminary results are presented. PMID- 1870326 TI - Glimpses into measurements of the microcirculation in skin. AB - There are instances when chronic disease states manifest as microvascular disturbances of the skin. Objective assessment of these disturbances would permit a better understanding of the causative factors and, in certain circumstances, influence decisions of clinical management. Recent advances in technology that permit such assessment non-invasively are evaluated in this review. PMID- 1870328 TI - Microwave imaging of tissue blood content changes. AB - Active microwave imaging gives information on the dielectric properties of of the body, allowing the collection of data that are distinct from, but complementary to, those available from other imaging methods based on different radiations. Two types of microwave imaging systems have been developed. The first is a planar system that irradiates the object with a plane wave and collects scattered phase and amplitude data at 1024 points on a parallel plane. The data can be reconstructed using a back propagation technique to give an image of the object. The second type of system is a tomographic scanner, consisting of a multiplexed 64-element circular array of waveguides. The waveguides are electronically scanned, alternately as sources and receivers, to give a complete scan of the object with no mechanical movement. A tomographic 'slice' of the object is reconstructed using spectral domain interpolation. Both systems work at 2.45 GHz with an incident power less than 1 mW cm-2 at the object and require a coupling medium (usually water) between the object and the source/receiver. Imaging parameters are appropriate for clinical use: a spatial resolution of 1 cm, measurement time of a few seconds and contrast resolution of around 1%. The effects of changes in perfusion on images of isolated animal organs are presented. Images have also been obtained, with both systems, of the internal dielectric structure of the forearm and of variations in dielectric properties due to changes of tissue blood content effected by application and release of tourniquets to the upper arm. Results show that these changes are well demonstrated by microwave imaging, and possible clinical applications are discussed. PMID- 1870329 TI - Quantitative measurement of sympathetic neuropathy in patients with diabetes mellitus. AB - Vasoconstriction occurs in the skin capillary blood flow of the healthy subject when posture changes from supine to standing. Using frequency analysis of the optical photoplethysmograph signal, a statistically significant difference (P less than 0.01) may be demonstrated between supine and standing positions in the lower frequency band (0.01-0.5 Hz) in the foot of normal subjects. This allowed us to develop a simple index: sympathetic power band change (SPBC). Patients with diabetes mellitus often suffer from degeneration in the sympathetic nervous system. This impairs the normal vasoconstrictor response to standing. We have applied the SPBC 'blind' to a group of diabetic patients. Such patients may be divided into three groups according to their SPBC indices: normals with SPBC greater than 2.6 (group A), intermediates with 2.6 greater than or equal to SPBC greater than or equal to 0.26 (group B) and poor with SPBC less than 0.26 (group C). All patients with retinopathy were in group C and five out of the six patients with electrophysiologically confirmed peripheral neuropathy were in group C. Frequency analysis of the photoplethysmograph signal has produced an index of sympathetic tone change when subjects move from supine to standing position. The application of this index to patients with diabetes mellitus shows some patients to have sympathetic vascular tone failure. PMID- 1870330 TI - Application of multilayer films to molecular sensors: some examples of bioengineering at the molecular level. AB - The Langmuir-Blodgett technique is now a well established method for producing ultra-thin organic films on solid surfaces. These layers could find wide ranging uses in electronic and optoelectronic devices, or even as the basis of artificial biological systems. In this paper the film deposition process is briefly reviewed. Examples of multilayers incorporating biological molecules are presented and possible applications for such films in sensing structures are briefly discussed. PMID- 1870331 TI - Current capabilities of rehabilitation robots. AB - Predictions are often made of intelligent and independently mobile robots for the disabled, and researchers are continually improving laboratory systems. Reductions in the cost of the technology involved may lead to affordable devices by the end of the decade. Less ambitious goals must be adopted by those projects wishing to distribute robotic aids to the disabled in the next few years. A modest selling price dictates the use of existing components. Even with the advent of more advanced robots, cost considerations may still make simpler devices on attractive alternative. Excessive optimism of future capabilities should be avoided, lest unrealistic expectations of current robotic aids hamper their development. Progress at all levels of rehabilitation robotics is complementary. PMID- 1870332 TI - Wear of cross-linked polyethylene against itself: a material suitable for surface replacement of the finger joint. AB - Cross-linking of polyethylene (XLPE) has dramatically improved its properties in industrial applications, and it may also have some application in the field of human joint replacement. Additionally it has the advantage of permitting a lower molecular weight base material to be used, so that components may be injection moulded rather than machined. This study therefore investigates the wear resistance of medical grade cross-linked polyethylene (XLPE), cross-linked by a silane-grafting process, with a molecular weight between cross links of 5430 g mol(-1). This first report investigates the wear resistance of XLPE against itself, because for certain joints, such as the metacarpo-phalangeal joint, the material may have a high enough wear resistance to allow both bearing surfaces to be made from it. Tests were carried out both on a reciprocating pin and plate machine with pins loaded at 10 and 40 N and also on a new finger joint simulator, which simulates the loads applied to and the movements of, the metacarpo phalangeal joint. An average wear rate of 1.8 x 10(-6) mm3 N-1 m-1 was found (range 0.9-2.75 x 10(-6) mm3 N-1 m-1). This is about six times greater than the wear rate of non-cross-linked ultra high molecular weight polyethylene (UHMWPE) against stainless steel, but for applications with low loading, such as the metacarpo-phalangeal joint, this material is shown to have adequate wear resistance. The coefficient of friction was 0.1, which is similar to that of UHMWPE on stainless steel. PMID- 1870333 TI - Isotope limb blood flow measurement in patients undergoing peripheral laser angioplasty. AB - A technique of isotope limb blood flow (ILBF) measurement employing Technetium labelled human albumin and a gamma camera, was used to assess limb perfusion in 19 patients undergoing percutaneous laser angioplasty, both before and one month after treatment. Twenty-three limbs with femoro-popliteal occlusions ranging in length from 3-35 cm (median 8 cm) were recanalized using an Nd-YAG laser and sapphire tipped optical fibre. Primary angiographic success was achieved in 19 lesions of which 6 re-occluded within the first month, and 13 remained patent with relief of symptoms. Clinically successful procedures were associated with a large increase in ILBF. However, normal blood flow was restored in only 54% of limbs. There was a slight decrease in limb perfusion after failed laser angioplasty but this was not statistically significant in this small series. Furthermore, there was no clinically apparent circulatory compromise, or need for urgent surgical bypass in failed cases. We conclude that ILBF is a useful means of assessing patients undergoing laser angioplasty, particularly for detecting small flow changes in patients who are unable to complete a standard exercise test. Its use can be recommended for assessing blood flow changes following other forms of limb revascularization. PMID- 1870334 TI - Validation of a quantitative radiographic technique to estimate pulsatile blood flow waveforms using digital subtraction angiographic data. AB - We have validated a new radiographic technique for determining pulsatile volume flow in arteries following an intraarterial injection of contrast material. Instantaneous blood velocities were estimated by generating a parametric image from dynamic angiographic images in which the image grey level represents contrast material concentration as a function of time and distance along a vessel segment. Adjacent concentration--distance profiles in the parametric image were shifted with respect to distance until a match occurred. A match was defined as the point where the sum of squares of the differences in the two profiles was a minimum. The distance translated per frame interval gives the instantaneous contrast material bolus velocity. We have validated the technique using an experimental phantom of blood circulation, consisting of a pump, flexible plastic tubing, the tubular probe of an electromagnetic flowmeter (EMF) and a solenoid, to simulate a pulsatile flow waveform, which includes reverse flow. Small boluses of contrast material can be injected at various positions in the circuit. Measurements of pulsatile velocity flow were taken at 40 ms intervals, using a tube of 6.6 mm internal diameter and an imaged tube length of 200 mm. The shape of the flow velocity waveform was faithfully reproduced but there was an overestimation of peak velocity of 40% at low velocities (peak velocity of 540 mm s-1), reducing to 19% at peak velocities of 964 mm s-1 with an underestimation of 16% at the peak velocities of 1899 mm s-1. The validation was repeated for distances ranging from 130 to 230 mm between injection and measurement sites and for imaged tube lengths varying from 200 to 20 mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870335 TI - Electro-rheological fluids: an introduction for biomedical applications. AB - The subject of electro-rheology is introduced to biological engineers in a concise manner to allow presentation of a procedure for effective quantitative evaluation of possible medical applications of this new technology. More detailed phenomena are included in the references. Characteristics of the current best available fluid are given in brief. PMID- 1870336 TI - Clinical experience in rehabilitation robotics. AB - A robotic workstation system for the disabled, based on a commercially available arm, was tested with six patients at the Spinal Injuries Unit, Odstock Hospital, Salisbury. A questionnaire was administered to those who used the system. Users evaluated the usefulness and performance of the system and commented on their reactions to the use of robots in rehabilitation. The users were generally favourable as regards the ease of use of the system using a two-switch input, operating a scanning menu. All users wanted the robot to be able to replay previously created routines, and the majority also wanted to be able to directly control the robot as well. The users were unsure about the potential usefulness of the system. Because a robot is by definition a flexible device, the context in which it is introduced will effect the way it is received by potential users. Tests in a hospital environment are useful because there is a high concentration of users in their own home situations will give a better idea of the usefulness of such devices. The system was not ideal from the point of visibility and layout, and was too large for use in a domestic environment. The layout was largely dictated by the geometry of the manipulator. Therefore a new workstation system has been constructed using a purpose built manipulator. This new system particularly aims to overcome the poor layout of the earlier workstation and benefits from feedback from users. PMID- 1870337 TI - Effect of postural change on common femoral artery volume flow, measured by duplex ultrasound, in normal subjects and patients with peripheral vascular disease. AB - Regulatory peripheral vasoconstriction occurs in response to adoption of the erect posture. Mildly ischaemic limbs are thought to exhibit near normal responses, but patients with rest pain show increases in blood flow on limb dependency. Previous methods of limb blood flow quantification (xenon clearance and venous occlusion plethysmography) have inherent difficulties when applied in these situations. We studied orthostatic responses in 12 normal subjects (aged 22 74 years (median 52) and 16 patients (aged 21-83 (median 48) with mild and severe peripheral vascular disease, using a duplex flowmeter system. In the normal subjects changes in the 60s mean, common femoral artery volume flow values were as follows (ml min-1 (1 SD]: 77 (83), -78 (116) and -190 (136), for elevation, dependency, and standing respectively. For claudicants (n = 7) the values were 18 (37), -112 (123) and -216 (103) respectively. In rest pain patients (n = 9) the responses were reversed, being -252 (124), 131 (89) and 184 (85) respectively. Significant differences were apparent between elevation, dependency and standing flows in each of the three groups (P less than 0.0001). Normal subject and claudicant responses on elevation and dependency differed significantly (P less than 0.0001 and 0.03 respectively). On standing, the responses were similarly significantly different. The rest pain group displayed characteristically different responses compared with both normal subjects and claudicants for each postural change (P less than 0.0001 in all cases). Duplex ultrasound volume flowmetry is non-invasive and offers an excellent method of quantifying physiological changes. PMID- 1870338 TI - Accuracy of colour Doppler ultrasound velocity measurements in small vessels. AB - Colour Doppler ultrasound offers the possibility of imaging small vessels not visible by B-mode alone. The colour Doppler image of velocities allows the course of small vessels to be imaged in the X-Y plane of the scan provided the Doppler frequency shift is of sufficient magnitude. This permits alignments of the Doppler cursor, allowing angle correction to provide true velocity measurements from the Doppler shift obtained. Before attempting to make velocity measurements, however, it is essential to be aware of the possible error in the Z plane caused by the thickness of the Doppler sample volume. To quantify this source of error, hydrophone and flow-rig measurements were performed on an Acuson 128 colour Doppler scanner with both 5 MHz linear-array and 3.5 MHz phased-array transducers. Measurements of the transmitted pulses using a point hydrophone showed that both probes employ approximately 3.5 MHz Doppler pulses (in both colour and pulsed Doppler modes). The two transducers have the same axial resolution. In colour Doppler mode the axial length of the sample volume increases automatically with depth by up to 0.5 mm. Measurements of colour and pulsed Doppler signal strength were obtained in a controlled flow rig. Both transducers produced accurate colour flow images of the phantom at their optimum depths; flow velocity errors due to Z-plane thickness are less than 5%. There was, however, substantial error outside these optimum conditions (up to 20%). PMID- 1870339 TI - Production of reliability proven physiological data for use in automated monitoring and diagnostic systems. AB - In recent years manufacturers of intensive care monitoring systems have introduced complex digital processing architectures that theoretically have enormous processing power. This power should allow the realization of many useful processing methodologies that up to now have only been research tools, e.g. the generation of reliable alarms, the implementation of predictive monitoring strategies and reliable diagnostic and treatment guidance to the clinical staff. However, before any of these methodologies can be successfully initiated, each must have accurate and reliable derived physiological data available to them, e.g. beat-by-beat heart rate and blood pressure. From the very nature of monitoring physiological quantities there will be much misinformation or 'noise' superimposed on the raw signal obtained from the patient. The major source of noise (as far as electrocardiogram (ECG) monitoring is concerned) is internal to the body and is electromyographic noise. This results from the contraction of skeletal muscles producing action potentials of similar magnitude and frequency to that of the ECG. Fortunately, nursing staff are very good at 'filtering out' any misinformation before recording any data (on a ward chart for instance). However, in completely automated systems, if this noise is not detected and eliminated or compensated for at an early stage in the processing chain, misinformation will result with potentially serious consequences. The recognition and elimination of such noise cannot be readily achieved using standard filtering techniques without serious degradation of information. This paper discusses the potential of modern digital system architectures developed for ECG monitoring. It analyses the noise that occurs on this physiological variable and demonstrates a novel method of eliminating such noise. PMID- 1870340 TI - Comparing subjective and objective assessments of the severity of vibration induced white finger. AB - The present staging of the disease severity of vibration induced white finger (VWF) is based on the patients' symptoms. Forty patients, with a history of VWF, with disease severity stage III or stage IV, on the Taylor-Pelmear scale, were investigated. Total, reactive hyperaemic blood flow to the hands was measured using an isotope limb blood flow (ILBF) technique. Skin blood flow patterns were assessed using a cold provocation test, followed by thermographic assessment of hand rewarming. Thermographic abnormalities were detected in 39 patients (97%). Decreased post-occlusive, reactive hyperaemic blood flow occurred in 29 patients (73%). There was no difference in skin blood flow patterns or in total hand blood flow between the stage III and stage IV groups. Reduction of postocclusive reactive hyperaemic blood flow may be indicative of occlusive lesions of the digital vessels. We conclude that the classification of the severity of VWF using subjective assessment, needs to be augmented by objective evidence of altered blood flow. PMID- 1870341 TI - IBEES Prize Lecture. The future of biomedical engineering. AB - Biomedical engineering is recognized as having developed an identity distinct from traditional engineering disciplines. The concepts which characterize this identity are outlined. The consequences of these are considered with particular attention to changing attitudes to professional specialization and work within the clinical environment. PMID- 1870342 TI - Altered sensitivity of digital blood flow to acute vibration in patients with vasospastic disease. AB - Fifteen patients with primary Raynaud's, 18 patients with vibration induced white finger (VWF) and 15 controls were exposed to sine wave vibration, with an amplitude of 0.15 mm and frequencies of 40, 80 and 120 Hz. Baseline digital blood flow was measured using venous occlusion strain gauge plethysmography. A digit was vibrated for 1 min and subsequent blood flow measurements were taken from both vibrated and non-vibrated digits. Vibration at 40 Hz causes a significant decrease in flow in the vibrated digits of the control group only (P less than 0.05, Wilcoxon test). Vibration at 80 Hz shows a significant decrease in blood flow in the vibrated digits of both the control and the VWF groups (P less than 0.005) and also in the non-vibrated digits of the VWF group (P less than 0.05). Vibration at 120 Hz significantly decreases blood flow in the vibrated digits of normal control, VWF and Raynauds group (P less than 0.001). The Raynaud's non vibrated digits also had decreased flow (P less than 0.005). These results imply that patients with established vasospastic disease are less sensitive to the direct effects of acute vibration than controls. The results also imply that vibration at 40, 80 and 120Hz affect digital blood flow in controls through local mechanism. Vibration at certain frequencies, appears to modulate blood flow in patients with vasospastic disease by acting through central mechanisms. PMID- 1870343 TI - Pasteurella multocida infection in a patient with AIDS. PMID- 1870344 TI - Primary testicular lymphoma with central nervous system involvement. PMID- 1870345 TI - Portal and superior mesenteric venous thrombosis following splenectomy. PMID- 1870346 TI - Upper extremity vaso-occlusive disease in a patient with giant cell arteritis. PMID- 1870347 TI - Ventricular septal rupture following myocardial infarction. PMID- 1870348 TI - The improving dental health of school children. PMID- 1870349 TI - Radiology case of the month. Cecal diverticulitis. PMID- 1870350 TI - Loss prevention case of the month. Same procedure--different standards. PMID- 1870351 TI - New research shows health care concerns. PMID- 1870352 TI - Contract law: some basic lessons. PMID- 1870353 TI - Clinical privileges and joint venture investments: two breaks for physicians. PMID- 1870354 TI - Effects of glycerol-induced acute renal failure on tissue glutathione and glutathione-dependent enzymes in the rat. AB - The activities of tissue glutathione (reduced and oxidized) and glutathione dependent enzymes such as glutathione S-transferase (GSH S-transferase), glutathione reductase (GSSG reductase) and glutathione peroxidase (GSH-Px) were determined for control and uremic rats. Acute renal failure (ARF) was produced by glycerol-water injection. Cytosolic and microsomal GSH S-transferase activity in the kidney was decreased by 38% and 15%, respectively. Hepatic microsomal GSH S transferase was also decreased by 40% in uremic rats. GSH-Px activity was decreased by 51% in the cytosolic fraction and 33% in the microsomal fraction in the kidney, but was not affected in the liver and whole blood. GSSG reductase activity was also decreased by 48% in the cytosolic fraction in the kidney of uremic rats. In whole blood, however, GSSG reductase activity was increased by 12 fold (0.66 +/- 0.12 mumol NADPH oxidized/min/ml blood in the control; 8.03 +/- 3.29 mumol NADPH oxidized/min/ml blood in uremia). Although the total glutathione concentrations were not significantly affected, the GSSG/GSH ratio, which is an indication of oxidative stress, was significantly increased in the liver and whole blood of uremic rats. In addition to the decreases in hepatic and renal GSH S-transferase activities, which is important in drug disposition, ARF caused decreases in GSSG reductase and GSH-Px activity, which are essential for the protection against lipid peroxidation. PMID- 1870355 TI - Action of metadoxine on isolated human and rat alcohol and aldehyde dehydrogenases. Effect on enzymes in chronic ethanol-fed rats. AB - Metadoxine (pyridoxine-pyrrolidone carboxylate) has been reported to accelerate ethanol metabolism. In the present work we have investigated the effect of metadoxine on the activities of isolated alcohol and aldehyde dehydrogenases from rat and man, and on the activity of these enzymes in chronic ethanol-fed rats. Our results indicate that in vitro metadoxine does not activate any of the enzymatic forms of alcohol dehydrogenase (classes I and II) or aldehyde dehydrogenase (low-Km and high-Km, cytosolic and mitochondrial). At concentrations higher than 0.1 mM, metadoxine inhibits rat class II alcohol dehydrogenase, although this would probably not affect the physiological ethanol metabolism. Chronic ethanol intake for 5 weeks results in a 25% decrease of rat hepatic alcohol dehydrogenase (class I) activity as compared with the pair-fed controls. The simultaneous treatment with metadoxine prevents activity loss, suggesting that the positive effect of metadoxine on ethanol metabolism can be explained by the maintenance of normal levels of alcohol dehydrogenase during chronic ethanol intake. No specific effect of chronic exposure to ethanol or to metadoxine was detected on rat aldehyde dehydrogenase activity. PMID- 1870356 TI - Learning and memory in rats exposed pre- and postnatally to alcohol. An attempt at pharmacological control. AB - Using conditioned-reflex methods for active and passive avoidance with punishment reinforcement, we found pronounced memory deficits in 12-week old rats exposed perinatally to alcohol (FAS rats). Impairment of memory was observed not only with the high dose of 9 g ethanol/kg body weight (ingested with tap water in a 6% solution) to which dams were exposed during pregnancy and lactation, but also with the ten-fold lower dose of 1 g ethanol/kg body weight (0.6% ethanol). The nootropic drugs citicholine, piracetam and meclofenoxate administered orally for five days before the training session were effective in decreasing memory deficits; particularly pronounced was the effect of piracetam and meclofenoxate. The benzodiazepine tranquilizer diazepam additionally impaired learning and memory in FAS rats. It is suggested that nootropics could be used to decrease the cognitive disturbances in some humans born to alcoholic mothers. PMID- 1870357 TI - Mechanisms of the angiotensin II effects on exploratory behavior of rats in open field. III. Modulatory role of GABA. AB - The effects of the octapeptide angiotensin II (AT II) and its interactions with GABA (gamma-aminobutyric acid) on the exploratory behavior of male rats in open field were studied. AT II (0.1 and 0.5 microgram i.c.v.) increased the open field behavior, mainly ambulation and rearing. GABA (100 micrograms i.c.v.) significantly reduced the effects of AT II. This influence of GABA was potentiated by subconvulsive doses of bicuculline. Our results demonstrate that the GABAergic system exerts an inhibitory control on pathways mediating the stimulatory effects of AT II on exploratory behavior in open field. The data also suggest close interactions between GABA AT II receptors. PMID- 1870358 TI - Pharmacokinetics of papaverine HCl upon intravenous route of administration in old and young beagle dogs. AB - This in vivo study was designed to compare the pharmacokinetics of papaverine HCl in young and old Beagle dogs following intravenous (i.v.) administration of papaverine HCl. Blood samples were analyzed by high performance liquid chromatography. The pharmacokinetic parameters were first determined using a curve fitting program (RESID), and then evaluated by SAS statistics. The plasma concentration-time profiles show that papaverine HCl pharmacokinetics is best described by an open two-compartment model. The only age-dependent significant difference in pharmacokinetic behavior between young and old Beagle dogs was found concerning the distribution rate constants. PMID- 1870359 TI - The binding spectra of rat renal and hepatic microsomal cytochromes P-450 with cyclosporine A. AB - Binding difference spectra of rat renal and hepatic cytochromes P-450 with cyclosporine A (CsA) were measured. In both cases reversed type I spectra were found with the absorbance maximum at 416 nm and minimum at 378 nm. Apparent spectral dissociation constant Kd and maximal absorbance difference delta Amax416 378 did not change substantially with the concentration of the CsA stock solution used. The results suggest that CsA might be biotransformed not only in the liver but also in the kidney. PMID- 1870361 TI - [Prevention of infection in liver transplantation]. PMID- 1870360 TI - Improved image quality during abdominal ultrasonography by clebopride + simethicone. AB - The use of clebopride + simethicone (Flatoril) was assessed as a possible solution to the problem of ultrasound imaging of the pancreas area. A statistically significant improvement was found in head and body imaging of the pancreas (76%). This is due to simethicone's antiflatulence effect and the movement of gas towards the intestine and colon as a result of clebopride's gastrointestinal emptying effect. PMID- 1870362 TI - [Personal experience with prevention and therapy of infection after 53 liver transplantations]. AB - An attempt was made to reduce the risk of infection following liver transplantation by means of selective bowel decontamination with tobramycin, polymyxin E and amphotericin B, as well as short-term systemic antibiotics with cephotaxim and tobramycin. After 53 consecutive orthotopic hepatic transplants performed in 51 patients between 1985 and 1987, a total of eight pneumonias occurred as the clinically most significant infection. Two pneumonias were caused by cytomegalovirus, one by Pneumocystis carinii, one by Candida and the remaining four by various bacteria. In 6 patients, bacteria were cultured from the blood, but only in one case was an indwelling catheter identified as the source of the septicemia. Taking all samples together, Streptococcus faecalis was the bacterium most frequently cultured, which was not covered by the prophylactic antimicrobial regime applied. Pseudomonas, however, and gram-negative bacteria were demonstrated much less frequently. Vaginal and oral Candida infections, as well as oral and genital herpes simplex infections, responded well to topical therapy with fungicide and aciclovir, respectively. Three patients developed cytomegalovirus (CMV) hepatitis. All five CMV infections were successfully treated with ganciclovir and hyperimmunoglobulin, as well as reduction of prophylactic immunosuppression. Out of 15 patients transplanted for posthepatitic cirrhosis, 7 developed a recurrence of the infection (5 hepatitis B virus) 2 hepatitis C virus) in the graft. Two died of the cirrhosis, three are still alive with cirrhosis but sufficient graft function, and one patient is suffering from chronic active hepatitis. One patient grafted for acute hepatic failure was able to clear the delta virus within 1 year post-transplant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870363 TI - [Acute stress-induced cholecystitis]. AB - Acute posttraumatic and postoperative cholecystitis is a serious and life threatening complication with mortality rates ranging from 10 to 50%. The pathogenesis is multifactorial: possible reasons are blood transfusions, dehydration, narcotics, shock and positive end-expiratory pressure (PEEP). Between 1980 and 1990 12 patients underwent surgery for acute cholecystitis. Six of them suffered from a so-called acute acalculous cholecystitis. Two patients died postoperatively. The symptoms are that of a "common" cholecystitis with leukocytosis, fever, abdominal distension and upper right abdominal pain. Sonography is a good method to establish the diagnosis and helps in the decision for cholecystectomy. Clinicians must remember the possibility of an acute cholecystitis in any surgical patient developing abdominal pain or unexplained fever. PMID- 1870364 TI - [Diagnosis and management of lower gastrointestinal hemorrhage. Retrospective analysis of 233 cases]. AB - In a retrospective analysis the diagnostic procedure was evaluated in patients with acute lower gastrointestinal bleeding. Bleeding sources were localized distally to the ligament of Treitz in 233 patients (1979-1988). Patients with hemorrhoidal bleeding were not included. Following exclusion of an upper gastrointestinal bleeding the diagnostic procedure was initiated with a recto /colonoscopy. Lesions were detected in 77% of the treated patients (n = 136). Angiography localized the bleeding in 68%, in combination with colonoscopy the identification of the bleeding source reached 86.5% in the treated patients. Following scintigraphy the bleeding source was determined in 89.7% of these patients. The sensitivity of colonoscopy (0.93) was superior to the angiography (0.78) and to the scintigraphy (0.75). Apart from neoplasms and adenomas angiodysplasia and Meckel's diverticula were the most common sources of the bleeding in patients who underwent operation. In 61 patients endoscopic therapy was performed, however, 6.5% of these patients had to be operated on later because of persistent bleeding. All together 79 patients underwent operation, 31 for bleeding and 48 for other reasons. 12 patients died, 6 of them were operated on for the bleeding, the other for neoplasms. PMID- 1870365 TI - [Initial results of image cytometric DNA analysis in the evaluation of prognosis in papillary thyroid cancer]. AB - In this study we analysed DNA-ploidy as a potential prognostic parameter in papillary thyroid carcinoma. Paraffin embedded histological material, obtained by resection from 19 patients with a papillary thyroid carcinoma, was selected for analysis. Tumor areas within the paraffin-embedded material were identified by HE stained reference sections. One 50 microns section was dewaxed, rehydrated and mechanically and enzymatically prepared to form a suspension of 10,000 cells/ml. 1 ml of the suspension, which contained bare nuclei with small rests of cytoplasma, was centrifuged on glass slides. The fixed nuclei were air-dried and stained by Feulgen SITS technique, which allows for the quantitative measurement of DNA. The DNA analysis was carried out with a computer-controlled single-cell cytophotometry. In contrast to using flow cytometry, only the tumor cells were measured by image-cytometry. Overlapping nuclei, dirt and other artifacts as well as inflammatory cells were efficiently eliminated. With DNA image-cytometry, we could differentiate between diploid (n = 13) and aneuploid (n = 6) tumors. Best prognosis with a survival rate of 92% after 103 months had patients with diploid tumors in contrast to patients with aneuploid tumors who did not survive more than 72 months. PMID- 1870366 TI - [Etiology and consequences of postoperative wound infection]. AB - The incidence of postoperative wound infection ranges between 4.6% and 36% after gastrointestinal operations respectively. To evaluate the factors which influence the postoperative wound infection we prospectively analyzed our patients between 1/1989 and 1/1990. 444 patients from three general surgical units of our clinic entered this study. The overall wound infection rate was 6.3%. We classified the patients into 3 operative groups: Group I: subcutaneous operations; Group II: intraabdominal operations without opening the GI-tract; Group III: gastrointestinal operations. Wound infection rate in group I was 1.8%, in group II 7.3% and in group III 13.7%. The differences were highly significant. Both univariate (chi 2-test) as well as a multivariate (Cox-Model) analysis were done. We figured out that classification of patients (p = 0.000), operation time (p = 0.009), operating room (p = 0.000), intensive care unit (p = 0.026), long-term antibiotic prophylaxis (p = 0.001), subcutaneous haematoma (p = 0.000) and length of closed drainage time (p = 0.001) are of significant value. In the Cox model the classification of patients into 3 groups surpassed all the other factors. Postoperative hospital stay was lengthened in patients with wound infection significantly (p = 0.0025). PMID- 1870367 TI - [Leiomyosarcoma of the vena cava. Case report and review of the literature]. AB - The leiomyosarcoma of vascular origin is a very rare tumor which is rarely recovered before the disease has reached an advanced stage because of non specific and late symptoms. This is a report of 3 cases with leiomyosarcoma of the vena cava and a review of the literature. A high local recurrence rate and high frequency of distant metastases are responsible for the bad long-term prognosis. Early hematogenous tumor spread is favored by intraluminal tumor growth. Only complete surgical resection--if necessary with vascular reconstruction--can improve the bad long-term prognosis. PMID- 1870368 TI - [Breast saving therapy of breast cancer--indications and consequences--results of a multidisciplinary consensus conference]. PMID- 1870369 TI - [Collagenous colitis]. AB - Collagenous colitis is now regarded by an overwhelming majority of authors as a clinicopathological entity and has been taken up as a such in many text-books and diagnostic atlases (Morson & Dawson, 1990, Fenoglio-Preiser et al., 1989, Whitehead 1985, Whitehead 1989). A good, detailed review of cases of collagenous colitis published up to 1988 was performed by Perri et al. Collagenous colitis was also presented to a wider medical public through a clinicopathological conference case at Massachusetts General Hospital (Case 29-1988). Finally it may be added that collagenous colitis has been included in the new fourth edition of Robbins Pathologic Basis of Disease (Cotran, Kumar, Robbins, 1989), where the possibility of an autoimmune disease is stressed. PMID- 1870370 TI - [Possibilities of cytodiagnosis in ascites]. AB - The examination of ascitic fluid is an important part in the diagnosis and control of gastrointestinal diseases. Different etiological conditions and pathological ways help develop different types of ascitic fluid. Variation of protein content (transudates/exsudates), variation of cells lead to different diagnosis. The following paper describes methods, diagnosis and differential diagnosis and limits of the cytological ascitic fluid examination. PMID- 1870371 TI - [Peroral and transhepatic cholangioscopy]. AB - Cholangioscopy is possible via the peroral or the transhepatic route. Cholangioscopy is of diagnostic value in tumour strictures and stenoses of the common bile duct. More important than diagnostic cholangioscopy is therapeutic cholangioscopy: with the technique of intracorporeal shockwave lithotripsy nearly all difficult CBD-stones may be successfully treated. 17 patients with 40 CBD stones were managed in mother-babytechnique in applicating intraductal shockwaves under direct visual control (electrohydraulic principle). Mechanical lithotripsy during ERCP had formerly failed in all patients. In 6 patients transhepatic cholangioscopy with intracorporeal shockwave lithotripsy was successfully performed. Patients had an operated stomach, so conventional ERCP with lithotripsy was not possible. 18 stones could be treated. As a total 23 patients with 58 CBD-Stones underwent cholangioscopy (median stone diameter 20 mm) with intracorporeal shockwave lithotripsy. Complete stone clearance was achieved in all cases, no serious complication occurred. PMID- 1870372 TI - [Insufficiency of the pelvic floor]. PMID- 1870373 TI - Reversal reactions in leprosy and their management. PMID- 1870374 TI - Association of mycobacterial-specific and Mycobacterium leprae specific antibody levels with clinical activity in tuberculoid leprosy: a comparative study of three serological enzyme-immunoassays. AB - The ELISAs for polyclonal antibodies against Mycobacterium leprae (ML-ELISA) and specific antibodies against epitopes on 35 kDa protein (SACT-ELISA) and phenolic glycolipid I (PG-ELISA) of M. leprae were evaluated comparatively in a group of 88 tuberculoid leprosy patients. The overall seropositivity rate with a battery of 3 tests (68%) was not significantly higher than that obtained with ML-ELISA alone (55%) for IgG class of antibodies. Seropositivities for SACT-ELISA and PG ELISA were, respectively, 38% and 26%. ML-ELISA for IgM class of antibodies was least sensitive, showing only 8% positivity. A significant correlation was noted between individual values of the three assays, but the positive proportions overlapped maximally in the case of ML-ELISA (IgG) and SACT-ELISA. Further, positivity for the latter two assays, particularly SACT-ELISA, showed significant associations with the extent of 'active' (largely untreated) infection. Immunoblotting revealed that the main antibody response was directed towards M. leprae antigens in the molecular weight range of 20-40 kDa and the densitometry results of this zone correlated significantly with corresponding SACT-ELISA and ML-ELISA (IgG) values. PMID- 1870375 TI - Mycobacteria in nerve trunks of long-term treated leprosy patients. AB - Mycobacteria were present in 4 out of 8 mixed peripheral nerve trunks from patients (3 BT and 1 BL) treated with DDS and/or MDT for periods ranging from 21 months to 8 years. Most of the bacilli appeared to be 'whole'. Nerve destruction with areas of granulomatous infiltration appeared more active than expected. Possible reasons for a continued presence of bacilli in treated nerves and its implications in 'relapse' are discussed. PMID- 1870376 TI - The significance of facial patches and type I reaction for the development of facial nerve damage in leprosy. A retrospective study among 1226 paucibacillary leprosy patients. AB - Charts of 1226 paucibacillary leprosy patients, registered between 1982 and 1987 were reviewed for recent facial nerve damage, facial patches and the presence of Type I reaction. Twenty-six (2.1%) patients with recent lagophthalmos were identified. In a great majority (85%) patients with recent lagophthalmos showed significant patches over the malar region or around the eye, at the same side as the nerve damage together with clinical signs of Type I reaction. This combination of significant patches in certain locations and Type I reaction seems to be a pre-condition for facial nerve damage. The clinical implication is that a small group of patients may be identified, who are at risk of facial nerve damage. By examining these patients more carefully it will be possible to detect nerve damage early and to prevent permanent damage of the facial nerve by timely treatment with an appropriate steroid regimen. PMID- 1870377 TI - Treatment of recent facial nerve damage with lagophthalmos, using a semistandardized steroid regimen. AB - Twenty-seven patients with borderline leprosy and facial nerve damage of less than or equal to 6 months duration (36 eyes) were treated with a semistandardized regimen of steroids (the average starting dose was 25-30 mg, duration 5-6 months) on an outpatient basis. Red and raised reactive patches were usually present in the upper malar area or around the eye(s) in patients with recent lagophthalmos. The lid gap was measured in millimetres during gentle and strong closure. After completion of the steroid course 75% of the eyes had complete closure or only a slight gap of less than or equal to 2 mm on gentle closure. Steroids were found to be beneficial and safe, in the dosage that we prescribed. PMID- 1870378 TI - Patterns of erythropoiesis and anaemia in leprosy. AB - A total of 128 leprosy patients were investigated for the morphological type of anaemia, the underlying disturbances in iron metabolism and patterns of erythropoiesis and other cytomorphological changes in the bone marrow. The anaemia was a mild to moderate degree in paucibacillary (PB) leprosy, while in multibacillary (MB) leprosy it was of a severe degree. Iron deficiency was observed in only a few patients. Impaired iron utilization as observed in a anaemia of a chronic disorder was a common finding in MB leprosy (41.7%) and more so in new cases (50%). Megaloblastic erythropoiesis was also more frequent in MB leprosy (45.2%) as compared to PB leprosy (16%), accounting for the severe degree of anaemia in the former type. In 17.2% of the total patients (MB, 21.4%; PB, 9%) both megaloblastic erythropoiesis and features of impaired iron utilization were observed in bone marrow. Disturbances in iron metabolism and erythropoiesis were also observed but to a lesser degree in patients receiving specific antileprosy treatment. Irrespective of the type of disease and duration of treatment, increasing frequency of acid-fast bacillia (AFB) positivity and granulomas was observed in the bone marrow with an increasing severity of anaemia. PMID- 1870379 TI - Effect of dapsone on haemoglobin concentration in patients with leprosy. AB - Haemolysis and frank anaemia from dapsone therapy of leprosy has been long recognized. However, the frequency and severity of this side-effect have not been well documented. We report herein a retrospective analysis of the effect of daily dapsone (generally 100 mg/day) on the haemoglobin concentration of 100 leprosy patients undergoing initial chemotherapy. The average haemoglobin was found to fall significantly by almost 2 g/dl, from 14.25 +/- 1.27 g/dl to a nadir of 12.31 +/- 1.61 (P less than 0.001). Eighty-three percent of patients had a fall of haemoglobin concentration of 1 g/dl or more, while in 16% of patients the haemoglobin fell greater than or equal to 3 g/dl. Increasing age was found associated with an increased magnitude of dapsone-related haemolysis (P less than or equal to 0.004). Decreasing the daily dose of dapsone was associated with an increased haemoglobin concentration (P less than 0.001%). We have concluded that dapsone commonly results in not only haemolysis but a significant decrease in haemoglobin concentration. This may have serious clinical implications, especially in endemic areas, where, owing to nutrition, malaria, and intestinal parasitism, the haemoglobin concentration is already compromised. PMID- 1870380 TI - A controlled therapeutic trial in paucibacillary leprosy comparing a single dose of rifampicin with a single dose of rifampicin followed by one year of daily dapsone. The Collaborative Study Group for the Treatment of Leprosy in Zaire. AB - The cure rates of two treatment regimens in PB leprosy were compared in a prospective randomized trial: treatment U consisting of a single dose of rifampicin 40 mg/K bodyweight, and treatment A of rifampicin 1500 mg in a single dose, followed by one year of daily dapsone 100 mg. In patients with a BI = 0, the cure rates evaluated on the basis of histopathology of skin biopsies, were identical for the two regimens but in patients with a BI = 1, cure and relapse rates were unacceptable. For this reason and particularly the need to separate patients on the basis of the BI in skin biopsies, the single dose regimen does not appear to be suited for wide-scale application. PMID- 1870381 TI - Longitudinal study on relapses of leprosy in Polynesian multibacillary patients on dapsone monotherapy between 1946 and 1970. AB - Between 1946 and 1970, 295 new leprosy patients were detected in French Polynesia, of whom 145 were multibacillary. Of these 145, put on dapsone monotherapy, 131 reached bacteriological negativity in a period of time ranging from 2 to 12 years (average 4.72 years) and were followed-up for a period of time ranging from 19 to 43 years (median follow-up period after bacteriological negativity; 18 years). Among the 131 patients, 36 relapses were detected, the first one 4 years after bacteriological negativity and the last one 26 years after. The crude relapse rate was 27.5%, the risk of relapse was 1.39 per 100 patient years and the cumulative relapse probability, calculated using the lifetable method, reached 0.38 +/- 11 by year 31 of the study. From these findings one may assume that, at least in French Polynesia, one-third to one-half of multibacillary patients put on dapsone monotherapy would relapse if still present 36 years after bacteriological negativity. Such results re-emphasize the need for leprosy patients to be treated with multidrug therapy as recommended by WHO. PMID- 1870382 TI - A retrospective study on seven years of multiple drug treatment for paucibacillary and multibacillary leprosy, in Bayara General Hospital, Nigeria. AB - In Bauchi State, Nigeria, a retrospective study was carried out among 973 patients on multidrug therapy (MDT), multibacillary (MB) and paucibacillary (PB), and 118 patients on a dapsone-clofazimine therapy. These patients were registered between January 1983 and September 1989. Clinical results and the problem of defaulting were investigated. The most important conclusions drawn are: although relapses occur, MDT-PB can be a valuable treatment; health education, shorter duration of treatment and permission to come less often lower the default rate, but in spite of this, the distance between home and clinic remains a problem. PMID- 1870383 TI - The protective effects of methyl cellulose and conoid shields for lagophthalmos and corneal hypaesthesia in leprosy. AB - Lagophthalmos and corneal hypaesthesia are amongst the most frequently encountered lesions in leprosy and they can easily give rise to blindness. Many measures (such as eye drops, protective conoid shields, muscle exercises, surgical treatment etc.) have been used to protect the eyes under such circumstances and this paper examines the protective role of methyl cellulose and conoid shields in 41 patients. All of them had lagophthalmos (5 mm or more) and corneal hypaesthesia. They were divided into three groups. Group one had 15 leprosy control patients (27 eyes) who did not use methyl cellulose or eye shields. Group two had 16 leprosy patients (28 eyes) and they used methyl cellulose and eye shields when they felt discomfort in their eyes. Group three had 10 leprosy patients (17 eyes) and they used methyl cellulose and eye shields regularly. Statistically significant improvement was seen in group three. Further studies on larger groups of patients including the effects of different concentrations of methyl cellulose, on Schirmer test and tear break up time, may be of value. PMID- 1870385 TI - Localized borderline lepromatous leprosy. AB - A 48-year-old soldier presented with 3 small leprosy lesions localized over the flexor area of the forearm. There was no nerve thickening and clinically the lesions looked like borderline-tuberculoid leprosy. However, these lesions demonstrated a bacteriological index (BI) of 4+ while no acid-fast bacilli (AFB) could be demonstrated from any other site of the body. A lepromin test was negative. Histologically evidence of borderline lepromatous leprosy was conspicuous. The case was diagnosed as localized borderline lepromatous-leprosy and treated with multidrug therapy. After 1 year of treatment, the lesions regressed, a lepromin test was positive (5 mm) and the BI from the lesions fell to 1+. PMID- 1870384 TI - Persistent reaction in paucibacillary leprosy: case reports. AB - Three patients of histopathologically confirmed borderline-tuberculoid leprosy showing no acid-fast bacilli and with lesions confined to the face, 2 on the cheek and 1 on the forehead, were given multidrug therapy as recommended by the WHO for paucibacillary cases. Within 3 months the lesions showed signs of upgrading (or reversal) reaction which was substantiated by histopathology. In 1 patient the facial nerve was affected leading to facial palsy. The lymphocyte transformation test did not show a significant rise. All 3 patients were given oral prednisolone for periods varying between 5 and 7 months, but the response was poor except in 1 patient in whom the facial palsy responded favourably. Injections of sodium antimony gluconate tried in 1 patient after stoppage of steroids did not control the reaction. After 18 months of regular follow-up during therapy, the cutaneous reaction in the patient with facial nerve involvement subsided leaving significant atrophy. However, in the other 2 patients the skin lesion persisted with clinical and histopathological evidence of upgrading reaction. The reasons for the unnatural persistence of reaction in these patients is not clear. PMID- 1870386 TI - Ten years of activities of the German Leprosy Relief Association in Senegal. PMID- 1870387 TI - Comment: Clofazimine-induced lymphoedema. PMID- 1870389 TI - Field detection of early neuritis in leprosy. PMID- 1870388 TI - Comment: The use of honey and sugar for the treatment of ulcers in leprosy. PMID- 1870390 TI - Wooden box for the taking, fixation and transport of slides for slit-skin smears in leprosy under field conditions. PMID- 1870391 TI - [Reflexotherapy in the postoperative period]. PMID- 1870392 TI - [Control testing of knowledge in physiotherapy]. PMID- 1870393 TI - [Modern anti-arrhythmia drug agents]. PMID- 1870394 TI - [Ultrasonic diagnosis in neurology and neurosurgery]. PMID- 1870395 TI - [Syringomyelia]. PMID- 1870396 TI - [Facial nerve neuropathy]. PMID- 1870397 TI - [The immunological aspects of blood transfusion]. PMID- 1870398 TI - [The potentials of ultrasonic diagnosis in obstetrics]. PMID- 1870399 TI - [The most important clinical manifestations of lung diseases and the care of patients]. PMID- 1870400 TI - [The procedure for releasing drugs and the organization of drug storage in treatment and prevention institutions]. PMID- 1870401 TI - [First aid in potassium permanganate poisoning]. PMID- 1870403 TI - [High myopia and its treatment possibilities]. PMID- 1870402 TI - [Spinal fractures and medical first aid]. PMID- 1870404 TI - [Rheoencephalography as a method for studying the cerebral circulation]. PMID- 1870405 TI - [Diet No. 15 (winter-spring)]. PMID- 1870406 TI - [Social hygiene research on children's health]. PMID- 1870407 TI - [Cardiac glycosides]. PMID- 1870408 TI - [Horsetail]. PMID- 1870409 TI - [Medical care at the family level]. PMID- 1870410 TI - [Evaluation of the efficacy of L-acetylcarnitine and tiapride combination in elderly patients with behavioral disorders]. AB - The study assessed the efficacy of the association of L-AC and tiapride in the treatment of behavioural and psychiatric symptoms due to cerebral decay. The study included 60 subjects, aged 65-80, who were subdivided into treated and control groups. Inclusion criteria included no previous psychiatric history and no general illness. Results demonstrate the usefulness of the association of the two drugs studied. PMID- 1870411 TI - [Group music therapy in the comprehensive management of psychosis]. AB - In this paper the Authors propose the use of group music therapy as an integrated part of the treatment of severe mental illness: borderline and psychotic cases. The therapeutical techniques used and their aims are fully described. There are four phases of treatment in the evolution of group music therapy; these take place successively over time and are repeated each time a new patient enters the group: 1) a motor phase in which patients dance, play games with movement and do physical exercises; 2) a receptive phase based on listening to music; 3) an active phase during which they make music and sing; 4) and a predominantly verbal phase during which patients discuss the emotions, thoughts and fantasies experienced while listening to music within the group. Lastly, the paper put forwards and hypothesis based on the therapeutical function of listening to music, taking into account the clinical aspects and concepts of dynamic psychology. PMID- 1870412 TI - [Notes on a group experience in a psychiatric department]. AB - The Author discusses some aspects of a group experience in a psychiatric department. The training characteristics of this activity are discussed in particular. PMID- 1870413 TI - [The evolution of a comprehensive community service system]. AB - The evolution of psychiatric care in the United States is still strongly influenced by the consequences of deinstitutionalisation. In some cases the process has generated a sort of transinstitutionalisation: at present, there are more intermediate public structures than a few years ago, whereas small residential units, experimentally self-managed by chronic patients, are also being established. With regard to the State of Illinois, current efforts are focused on the reduction of the number of psychosocial disabilities and the setting up of a wider range of rehabilitative programs. A comprehensive community service, connecting short-term and prolonged-stay hospital wards with community based facilities seems to represent the most promising combination. PMID- 1870414 TI - [Psychoimmunology. I. Relationships between neuroendocrine and immune systems]. AB - Recently a lot of studies have pointed to the relationships between the major homeostatic systems of the human body: the neuroendocrine system and the immune system. There is considerable evidence that they make up a psychoneuroendocrine immunologic network. In the present review the most interesting data concerning the relationships between the neuroendocrine system and the immune system are taken into account. PMID- 1870415 TI - [Psychoimmunology. II. The neuroendocrine system and the immune system in autism and schizophrenia]. AB - In this paper the Authors report on the immunologic alterations in two psychiatric disease: schizophrenia and infantile autism. While a lot of researches have been concluded on the immunologic alterations in schizophrenia, only a few data on infantile autism are available. Based on data from international literature the Authors advance some hypotheses on the role possibly played by the immune system in the pathogenesis of schizophrenia and infantile autism. PMID- 1870416 TI - [Neuroendocrine factors in postpartum blues]. AB - A very considerable proportion of women, estimated from 50 to 80 per cent, experience a noticeable period of emotional distress, usually mild or transistor, between the third and the tenth day postpartum (postpartum blues: PPB). The onset of this syndrome conform to a practically immutable of timing-symptoms are almost never noted before the third day postpartum (latent period). After this period, in approximately 10 per cent of women, occurs a depression: postpartum depression (PPD), and last to 8 weeks. Neuro endocrine factors in the pathogenesis of postpartum depression is discussed: thyroid, pituitary and adrenal cortex are reviewed. Considerable evidence support that the late postpartum syndromes are associated to psychological stress of childbirth with postpartum decrease of placental steroids, estrogen and progesteron, with high levels of pituitary prolactin. PMID- 1870417 TI - [The prevalence of smoking in psychiatric patients. The effect of "institutionalization"]. AB - The prevalence and other parameters concerning tobacco smoking were assessed in 100 outpatients with psychiatric disorders of axis I and II, according to DSM-III R criteria, and compared with those of 85 male psychiatric inpatients with forensic problems, recruited in a psychiatric hospital. The use of tobacco smoking was increased in psychiatric outpatients vs. the general pupulation and was very heightened in schizophrenic, as reported in earlier investigations; in the forensic sample both schizophrenic and non schizophrenic patients showed a very high prevalence. Therefore, the factor "institutionalization" does not modify the prevalence of tobacco smoking in schizophrenic--whose "smoking disposition" appears independent of the different social environments--while increasing the use in non schizophrenic patients. The positive correlation between tobacco smoking and schizophrenia is largely supported by these data and demands further investigation of its pathophysiologic mechanisms. PMID- 1870418 TI - [Evaluation of the efficacy and tolerability of fluoxetine in major depression, Multicenter clinical study]. AB - In an Italian multicenter study, 296 patients (115 males, 181 females) affected with major depression diagnosed according to the criteria of the DSM III-R, were treated for 8 weeks with 20 mg/die fluoxetine (Fluoxeren-Menarini s.r.l.). At the end of the therapy the mean scores on the Hamilton Depression Scale had improved considerably, going down from 27.42 to 10.05. 69.6% of the patients had improved by at least in the 50% in the HAM-D scores (responders). At the CGI the overall improvement was evaluated with a mean score of 2.05 (marked improvement), while the patients assessed themselves at the end of treatment as being from "improved" to "greatly improved". No significant differences in efficacy were found to depend on age, type of depression or response to previous treatment, though younger patients (18-40 years), and those with single or recurring episodes, with atypical depression and good response to other antidepressants, showed a more marked improvement. The tolerability of the drug was found to be good. The laboratory tests, ECG and body weight stayed within normal limits. PMID- 1870419 TI - Triiodothyronine (T3)-associated upregulation and downregulation of nuclear T3 binding in the human fibroblast cell (MRC-5)--stimulation of malic enzyme, glucose-6-phosphate-dehydrogenase, and 6-phosphogluconate-dehydrogenase by insulin, but not by T3. AB - The specific nuclear binding of triiodothyronine (T3) (NBT3) and the activity of malic enzyme (ME), glucose-6-phosphate-dehydrogenase (G6PD), and 6 phosphogluconate-dehydrogenase (6PGD) were studied in the human fibroblast cell (MRC-5). The overall apparent binding affinity (Ka) was 2.7 x 10(9) L.mol-1 estimated from kinetic studies of nuclear T3 binding, and 2.5 x 10(9) L.mol-1 estimated from equilibrium studies. The scatchard plots were curvilinear and composed of a high-affinity binding site with Ka1 3.4 +/- 0.7 x 10(9) L.mol-1 and maximal binding capacity (MBC) MBC1 57.0 +/- 11.9 fmol/mg DNA and a low-affinity binding site with Ka2 2.9 +/- 1.1 x 10(8) L.mol-1 and MBC2 124.7 +/- 22.1 fmol/mg DNA (n = 6). Incubation of cells with 6 nmol/L T3 for 20 hours reduced NBT3 to 62.2% +/- 15.7% (P less than .01, n = 11). The Ka estimated from kinetic studies was reduced to 6.7 x 10(7) L.mol-1, and the scatchard plots were linear, with Ka 4.5 +/- 1.6 x 10(8) L.mol-1 and MBC 137.0 +/- 44.6 fmol/mg DNA (n = 3) of the same magnitude as the low-affinity binding site in cells incubated without T3 (NS). The reduction in NBT3 was reversible and maximal at T3 concentrations saturating the high-affinity binding site and more than 58% of the total nuclear binding sites. The MRC-5 cell cytosol contained ME, G6PD, and 6PGD activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870420 TI - Importance of glucagon as a determinant of resting metabolic rate and glucose induced thermogenesis in obese women. AB - The long-term results of dietary treatment for obesity are often very poor. To predict the effect of a hypocaloric diet, it may be important to consider factors that could influence energy expenditure, especially those altered in obesity. Elevated plasma levels of glucagon are associated with obesity. In this study, the relationship of glucagon to resting metabolic rate (RMR) and glucose-induced thermogenesis (GIT) has been investigated. RMR and GIT, after ingesting 100 g glucose, were measured by indirect calorimetry in 25 obese premenopausal women (body mass index [BMI], 37.2 +/- 4.7 kg.m-2). RMR was significantly related to fat-free mass (FFM) (r = .50, P less than .005). A significant relation could be found between RMR and fasting glucagon levels (r = .36, P less than .05). Plasma glucose and insulin levels were not predictive for RMR. Mean GIT increased with increasing waist-hip circumference ratio (WHR) (r = .71, P less than 0.0001), confirming previous findings of our group. No relation was found between GIT and glucagon levels, neither in the basal state nor after glucose. The only important metabolic determinant was area under the curve (AUC) for glucose (r = .45, P less than .01), suggesting a higher GIT in obese women with impaired glucose intolerance. This suggests that the control of energy metabolism by the concentration of glucagon may be more important in the fasting state than after a meal. Plasma glucagon concentration should be considered in the evaluation of RMR. PMID- 1870421 TI - Urinary 3-hydroxydicarboxylic acids in pathophysiology of metabolic disorders with dicarboxylic aciduria. AB - Dicarboxylic aciduria occurs during increased mobilization or inhibited beta oxidation of fatty acids. In these conditions, a number of 3-hydroxydicarboxylic acids are excreted in the urine. These 3-hydroxydicarboxylic acids include 3 hydroxyadipic (3OHDC6), 3-hydroxyoctanedioic (3OHDC8), 3-hydroxydecanedioic (3OHDC10), 3-hydroxydodecanedioic (3OHDC12), and a number of unsaturated homologues. The metabolic origin of these 3-hydroxydicarboxylic acids is from the omega-oxidation of 3-hydroxy fatty acids. Subsequent beta-oxidation of the dicarboxylates yields lower-chain 3-hydroxydicarboxylic acids. A new defect in fatty acid oxidation characterized by increased urinary ratios of 3OHDC6, 3OHDC12, and unsaturated 3OHDC14s relative to 3OHDC10 is described. This pattern is consistent with a defect in long-chain 3-hydroxyacyl-CoA dehydrogenase (LHAD), which was confirmed by enzyme assay in fibroblasts. In contrast, patients with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency had lower ratios of 3OHDC6 and 3OHDC8 to 3OHDC10, consistent with a decreased activity of MCAD. Nonketotic dicarboxylic aciduria, other than MCAD and LHAD deficiencies, is shown to have a normal 3-hydroxydicarboxylic acid profile when compared with fasting normal controls. Since increased excretion of 3-hydroxydicarboxylic acids was observed in all patients with dicarboxylic aciduria, an increased excretion of these compounds is not an adequate criterion to suspect a defect in 3-hydroxyacyl-CoA dehydrogenases. The analysis of the metabolite ratios (3OHDC6 and 3OHDC12 relative to 3OHDC10) is a more useful indicator for defects in LHAD. PMID- 1870422 TI - Fuel metabolism in anorexia nervosa and simple obesity. AB - To examine insulin sensitivity and the relative contribution of different fuels to energy metabolism in anorexia nervosa and obesity, we measured oxidation (indirect calorimetry) of glucose, lipids, and proteins in the basal state and during an insulin clamp (+45 mU/m2.min) in 11 women with anorexia nervosa (age, 25 +/- 3 years; body mass index [BMI], 13.6 +/- 0.4 kg/m2; fat mass, 15.7% +/- 1.6%), eight obese women (age, 31 +/- 3; BMI 36.0 +/- 1.5; fat mass, 47.1% +/- 1.9%), and eight controls (age, 26 +/- 3; BMI, 21.8 +/- 0.9; fat mass, 25.7% +/- 3.6%). Expressed per lean body mass, (LBM), glucose disposal was equally reduced in anorectics (7.53 +/- 0.62 mg/kg LBM.min) and obese (6.80 +/- 1.07 mg/kg LBM.min) compared with controls (10.64 +/- 0.69 mg/kg LBM.min; P less than .01). The reduction in glucose disposal in anorectics was primarily due to a significant (P less than .01) reduction in glucose storage, while glucose oxidation was normal. In obese women, both storage and oxidation of glucose were reduced compared with controls (P less than .01). Basal energy expenditure was similar in anorectic, obese, and control subjects (20.6 +/- 1.00, 23.7 +/- 0.56, 23.2 +/- 1.36 cal/kg LBM.min, respectively). However, the contribution of glucose, lipids, and proteins to basal energy expenditure differed between anorectic (62%, 16%, 22%), obese (26%, 58%, 16%), and control (30%, 54%, 16%) subjects (P less than .05 v all). In conclusion, in anorexia nervosa, insulin stimulates glucose oxidation more than storage. In obesity, both components of insulin-stimulated glucose metabolism are impaired.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870423 TI - Effect of theophylline on urinary excretion of 3-methylhistidine in patients with lung disease. AB - Theophylline, which is commonly used for the treatment of lung disease, has been reported to stimulate lipolysis, glycogenolysis, and gluconeogenesis. This study was initiated to investigate whether theophylline therapy also induces catabolic changes in protein metabolism and thus provides additional substrates for energy metabolism. Urinary excretion of 3-methylhistidine (3-MH) as an index of myofibrillar protein catabolism was measured at the end of a 7-day treatment period with theophylline and a 5-day basal untreated control period in eight patients with stable chronic obstructive pulmonary disease (COPD), eight patients with stable asthma, and eight normal healthy volunteers. Basal urinary 3-MH excretion and 3-MH/creatinine ratios, and nutritional indices assessed were not different in the three groups. Under similar drug (except theophylline), dietary, and activity regimens, comparison of the two experimental periods showed that theophylline increased mean urinary 3-MH excretion and 3-MH/creatinine ratios in all three groups of subjects. These changes were significant in the COPD and asthmatic patients (mean 3-MH +/- SD, mumol/d: basal, 176 +/- 46 v 206 +/- 46; and basal, 190 +/- 27 v 216 +/- 45, respectively, P less than .05) and persisted when 3-MH values were normalized to creatinine excretion (15% to 38%, P less than .005). In contrast, the mean increment was marginal in the group of normal volunteers and this discrepancy of effect between groups may be attributed to dietary noncompliance. Furthermore, the response of the COPD group was significantly greater than the asthmatic and control groups (1.8x and 11.3x, respectively, P less than .05). In conclusion, these results suggest that theophylline may enhance myofibrillar protein degradation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870424 TI - Mineral homeostasis in obesity: effects of euglycemic hyperinsulinemia. AB - We explored the effects of insulin on mineral homeostasis in five lean and six moderately obese nondiabetic premenopausal women. Serum and urine minerals were measured before and during the steady-state phase of a euglycemic insulin clamp. Each subject participated in two insulin clamp studies on separate days at insulin infusion rates of 10 and 40 mU/m2/min. Euglycemic hyperinsulinemia was associated with (1) a significant increase in urinary calcium excretion when expressed per minute with no change in total serum calcium; (2) a decrease in urine and serum phosphate; (3) a decrease in serum potassium with no change in urine potassium; and (4) no measurable effects on urine or serum sodium. At any given insulin level, the obese individuals excreted significantly more calcium, phosphate, and potassium per minute than lean controls. While insulin administration had no effect on serum parathyroid hormone (PTH) or vitamin D levels, baseline serum 1,25(OH)2D concentration was significantly higher and serum ultrafilterable calcium was significantly lower in obese subjects than in lean controls. PMID- 1870425 TI - Effects of fitness level and the regional distribution of fat on carbohydrate metabolism and plasma lipids in middle- to older-aged men. AB - Many cross-sectional studies have demonstrated the influences of fitness level or the regional distribution of fat on lipid and carbohydrate metabolism; however, the relative contribution of these two variables in the same subjects has not been extensively examined. The purpose of this study was to determine the impact of regional adiposity on plasma lipids and carbohydrate metabolism in middle- to older-aged men with a wide range of fitness levels. Forty-six sedentary and exercise-trained men (age [mean +/- SE], 52.8 +/- 0.88 years) were included in this study. Fitness level was assessed by (a) time to exhaustion, and (2) maximal oxygen uptake achieved during an incremental treadmill test. Plasma lipid levels were determined in the basal, fasting state. Carbohydrate metabolism was evaluated by the glucose and insulin responses (total glucose and insulin areas under the curve, insulin sensitivity index [ISI]) to a 75-g, 2-hour oral glucose tolerance test (OGTT). Abdomen to hip ratio (AHR) was used as the index of regional adiposity. Multiple regression analysis indicated that fitness level and the percentage of body fat were significant predictors (approximately 56% of total variance) for total insulin area under the curve and the ISI. A comparison between the sedentary and trained subjects showed that training resulted in an improved ISI at an equal AHR. Fitness level was also the only significant multiple regression predictor for high-density lipoprotein (HDL)-cholesterol (25% of total variance) and accounted for the greatest amount of variance in triglyceride levels (34%), although AHR was also a significant predictor (6%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870426 TI - Tumor necrosis factor-alpha and anorexia--cause or effect? AB - Tumor necrosis factor-alpha (TNF-alpha) is a principal cytokine that may induce weight loss in malignancies and certain chronic infections. Short-term caloric deprivation has been found to facilitate in vitro TNF-alpha production, while increased spontaneous production of TNF-alpha has been found in patients with anorexia nervosa (AN). In the present work, we studied in vitro TNF-alpha production in other types of chronic undernutrition and the changes in TNF-alpha production during the refeeding of patients with AN. Undernutrition was evaluated by calculating fat body mass (FBM) from skinfold measurements and lean body mass (LBM) by total body potassium (TBK) counting. Spontaneous and induced TNF-alpha production by peripheral blood mononuclear cells (PBMC) was studied in six chronically malnourished patients with no intercurrent infections, seven patients with AN, and 16 age-matched normal healthy subjects. Spontaneous TNF-alpha production was in the normal range in the chronically undernourished subjects (4.3 +/- 1.5 v 5.0 +/- 1.9 U/mL), but significantly increased in the seven patients with AN (221 +/- 327 v 5.0 +/- 1.9 U/mL, P less than .0006). During refeeding of patients with AN, TNF-alpha production decreased to the normal range concomitantly with weight gain. We concluded that chronic undernutrition, in general, is not always associated with increased TNF-alpha production and that it still remains to be determined whether TNF-alpha plays a primary role in the pathogenesis of AN. PMID- 1870427 TI - Blunted growth hormone (GH) responsiveness to GH-releasing hormone in obese patients: influence of prolonged administration of the serotoninergic drug fenfluramine. AB - The aim of the present study was to ascertain if reduced central serotoninergic activity might contribute to the well-known blunted growth hormone (GH) response to GH-releasing hormone (GHRH) in obese patients. Thus, we studied the effect of prolonged stimulation of the serotoninergic system by fenfluramine (FF; 60 mg twice daily for 7 days) on GHRH-induced GH release in nine obese and seven normal subjects. In controls, GHRH (100 micrograms intravenously [IV]) injection increased GH levels from 2.3 +/- 1.8 (+/- SE) to 18.5 +/- 2.8 mU/L, P less than .002. FF administration enhanced both basal and GHRH-stimulated GH levels (peak, 38.4 +/- 8.3 v 6.9 +/- 2.6 mU/L, P less than .002). This response was significantly higher (P less than .02) than in pretreatment. In obese patients, GH responsiveness to GHRH was slight (peak, 7.1 +/- 2.0 v 0.6 +/- 0.18 mU/L, P less than .01) and lower (P less than .01) than in controls. FF administration did not affect this response. In controls, the enhanced FF-induced GH release after a maximal dose of GHRH indicates that serotoninergic activation influences GH secretion and that the mechanism involved is independent of endogenous GHRH. In obese patients, we found a blunted GH responsiveness to GHRH that was not affected by FF, thus supporting the hypothesis that the serotoninergic control on GH release is impaired. PMID- 1870428 TI - Contributions of regional adipose tissue depots to plasma lipoprotein concentrations in overweight men and women: possible protective effects of thigh fat. AB - Anthropometry and dual-photon absorptiometry (DPA) were used to examine associations of regional adiposity with plasma lipid, lipoprotein, and lipoprotein subfraction mass concentrations in moderately overweight men and women. Among 130 women, waist to thigh girth ratio (WTR) correlated with triglycerides (TG) (r = .33, P less than .0001) and negatively with high-density lipoprotein (HDL)-cholesterol (HDL-C) (r = -.37, P less than .0001) concentration, as expected. While WTR did not correlate with low-density lipoprotein (LDL)-cholesterol (LDL-C) it correlated positively with the mass subfraction of small (Sfo, 0 to 7) LDL (r = .38, P less than .0001), and negatively with large (Sfo, 7 to 12) LDL (r = -.31, P less than .01). Among 133 men, similar though weaker relationships were found. Thigh girth correlated positively with HDL and HDL2-C and mass, and with LDL particle size among women. Multivariate analysis suggests that association of WTR with lipoprotein values known to carry risk of coronary heart disease (CHD) are due at least as much to effects of thigh girth as to deleterious effects of waist girth. Estimates of fat weight in thigh and abdominal regions by DPA support thigh fat as contributing to these effects of thigh girth. Thigh fat may contribute to lipoprotein profiles that predict lower risk of cardiovascular disease. PMID- 1870429 TI - Lack of effect of salt on the glucose and insulin response to mashed potatoes, white rice, and lima beans. AB - The effect of 4.25 g of table salt on the insulin and glucose response to three forms of carbohydrate with varying glycemic indices was studied. There was no statistical difference in the peak response or area under the glucose or insulin curves for any of these foods in the presence of salt. It is concluded that salt has no effect on the absorption of starches. PMID- 1870430 TI - Influence of gliclazide on glucose-stimulated insulin release in man. AB - Although sulfonylureas (SU) are widely used in the management of patients with non-insulin-dependent diabetes mellitus (NIDDM), there is still debate about their mechanism of action on the pancreatic beta cell. It is unclear whether the effect of SU on insulin release is additive to the effect of glucose, or whether SU act by increasing pancreatic beta-cell sensitivity to glucose (a shift in the dose-response curve of glucose-stimulated insulin release without a change in maximum release). To address this issue, we assessed the influence of the SU gliclazide on glucose-stimulated insulin release in eight healthy male volunteers. Sixty-minute hyperglycemic glucose clamps (blood glucose levels: 8 mmol/L, a submaximal stimulus; and 32 mmol/L, a maximally stimulating concentration) were performed with and without prior oral administration of gliclazide (80 mg) 30 minutes before the glucose clamp. Mean plasma C-peptide increment at 5 minutes (first-phase secretion) obtained during the 8-mmol/L hyperglycemic clamp, was higher on the gliclazide study day than on the control day (1.07 +/- 0.10 v 0.88 +/- 0.10 mmol/L, P less than .05), whereas no difference in plasma C-peptide response was observed during the 32-mmol/L hyperglycemic clamp. Mean plasma C-peptide increment obtained at the end 60 minutes; (second-phase secretion) of the 8-mmol/L hyperglycemic clamps was higher on the gliclazide study day than on the control day (1.36 +/- 0.13 v 1.09 +/- 0.09 mmol/L, P less than .02). No difference was observed in plasma C-peptide response at the end of the 32-mmol/L hyperglycemic glucose clamps.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870431 TI - Characterization of plasma lipoproteins in patients heterozygous for human plasma cholesteryl ester transfer protein (CETP) deficiency: plasma CETP regulates high density lipoprotein concentration and composition. AB - To understand the role of human cholesteryl ester transfer protein (CETP) in plasma lipoprotein metabolism, CETP activity and mass levels, lipoprotein and apolipoprotein concentrations, and the size of high-density lipoprotein (HDL) were determined in 15 heterozygotes and compared with those of four homozygotes and 20 normolipidemic controls. Plasma CETP activity and mass were totally deficient in the four homozygotes for CETP deficiency, while heterozygotes had approximately half the level of normals. CETP activity positively correlated with CETP mass levels (r = .95, P less than .001). No significant difference was observed in the level of low-density lipoprotein (LDL)-cholesterol among the three groups. The concentration of HDL2-cholesterol in the heterozygotes was approximately twice as high as that in controls, while that of homozygotes was sixfold higher than that in controls. No significant difference in the HDL3 cholesterol level was observed among the three groups. The HDL2-cholesterol to HDL3-cholesterol ratio of homozygotes was sixfold higher than that of controls, while heterozygotes showed intermediate values between homozygotes and controls. Negative correlations were found between CETP activity and HDL2-cholesterol level (r = -.884, P less than .001) and between CETP mass and HDL2-cholesterol level (r = -.829, P less than .001). Plasma apolipoprotein (apo) A-I, C-III, and E were markedly increased in homozygotes, but the differences between normal and heterozygotes were not statistically significant. The HDL size of homozygotes, determined by high-performance liquid chromatography (HPLC), was large, whereas that of heterozygotes was intermediate between homozygotes and normals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870432 TI - Studies on the relationship between serum colloidal reactions (ZTT and TTT) and IgG subclasses, especially IgG1 and IgG2. AB - The relationship between zinc sulfate turbidity test (ZTT and thymol turbidity test (TTT), and IgG subclasses, especially IgG1 and IgG2, was studied. Serum colloidal reactions of specimens from patients with IgG-myeloma usually show abnormally high values in ZTT and low values in TTT. But in some cases, values in ZTT and TTT are both low, and in a few cases both values are abnormally high. In order to see the reason why IgG-myelomas are classified into these three groups according to serum colloidal reactions. IgG subclasses of monoclonal proteins (MPs) isolated by zone electrophoresis were determined by immunodiffusion with anti IgG-subclasses. Results revealed that IgG1-myeloma showed high ZTT and low TTT and IgG2-myeloma showed low ZTT and TTT. Only two out of our 29 cases with IgG-myeloma showed high ZTT and TTT. MP from one of them belonged to IgG1-kappa and that from the other to IgG2-lambda. We checked the relationship between turbidity tests and electrophoretic mobility of MP and also that between these tests and L-chains' type of MP, but did not find any relationship between them. These findings suggest that IgG1 innately reacts with ZTT but not with TTT, while IgG2 does not react with any of these tests. MP from cases showing high values in both ZTT and TTT may have a special idiotype. PMID- 1870433 TI - The presence of cis-9,10-methylene hexadecanoic acid in Yersinia enterocolitica. AB - The fatty acids of Yersinia enterocolitica were investigated by Abbas and Card. In their report, they stated that the major fatty acids were C16:0, C16:1, C17:0 and C18:1 and branched or cyclopropane side-chain fatty acids could not be detected. We, however, found a moderate amount of cyclopropane side-chain fatty acid. We could determine that this fatty acid was cis-9, 10-methylene hexadecanoic acid by gas-liquid chromatography, gas chromatography-mass spectrometry, silver-nitrate-treated TLC and PtO2 catalyzing hydrogenation method. PMID- 1870434 TI - Pattern of shedding of small, round-structured virus particles in stools of patients of outbreaks of food-poisoning from raw oysters. AB - The pattern of shedding of the small, round-structured virus (SRSV) particles in the stools of patients who suffered from food-poisoning due to raw oysters was investigated. The duration and concentration of fecal shedding of the SRSV particles were studied by electron microscopic examinations of stool specimens obtained during the course of illness to see a relation of viral shedding to day of illness. It was found that the fecal shedding of the SRSV particles occurred within five days of illness; thereafter, the concentration of the SRSV particles in feces rapidly decreased within a few days during the course of illness. PMID- 1870435 TI - Mycolic acid-containing glycolipid as a possible virulence factor of Rhodococcus equi for mice. AB - By the use of various Rhodococcus equi strains differing in the length of carbon chains of glycolipid, we examined whether the glycolipid, glucose monomycolate, was contributing to the virulence of R. equi for mice. R. equi strains with longer carbon chain mycolic acid showed a higher virulence as determined by lethality and granuloma formation in mice than those with shorter ones. When purified glycolipid was injected into mice, granuloma formation and liver damage were most prominent with the glycolipid having longer carbon chain mycolic acid. Only a representative strain with longer carbon chain mycolic acid persisted in the spleen of mice after intravenous injection, while a strain with shorter carbon chain mycolic acid was readily eliminated. These results suggested that glycolipid was at least one of the virulence factors of R. equi and that the carbon chain length of mycolic acid might be critical in the expression of virulence. PMID- 1870436 TI - The 106-kilobase plasmid of Salmonella braenderup and the 100-kilobase plasmid of Salmonella typhimurium are not necessary for the pathogenicity in experimental models. AB - Among 1.041 clinical isolates (77 serovars) of Salmonella which had been derived from cases with acute enterocolitis, 601 (58%) contained one or more plasmids. Large serovar-specific plasmids were seen in 95 of 307 isolates (31%) of Salmonella typhimurium, in 34 of 34 isolates (100%) of Salmonella enteritidis and in 36 of 38 isolates (94.7%) of Salmonella braenderup: the sizes of which were 100, 60 and 106 kilobases (kb), respectively. In order to determine the role of these plasmids in pathogenicity for enterocolitis, the plasmids were eliminated from some strains of S. braenderup and S. typhimurium and the pathogenicity of the plasmid-less strains was compared with that of the parent strains by invasiveness to HeLa cells, fluid accumulation in the rabbit ligated ileal loop, lesion of mucosal tissue and the Sereny test. The virulence of all the plasmid less strains was as strong as that of the plasmid-bearing strains in these pathogenicity assay systems. We therefore concluded that the 106-kb plasmid of S. braenderup and the 100-kb plasmid of S. typhimurium are not necessary for their pathogenicity in the experimental models: invasiveness to HeLa cells, fluid accumulation in the rabbit ligated ileal loop, and Sereny test. PMID- 1870438 TI - Factors influencing the in vitro growth of Mycobacterium leprae: effect of sulfhydryl compounds. AB - In an attempt to determine the factors that influence the in vitro growth of Mycobacterium leprae in DH medium, the effects of sulfhydryl compounds were studied. Growth of M. leprae was monitored using two biochemical indicators. Only the sulfhydryl compounds, in reduced form, containing carboxyl group could support the growth of M. leprae. Higher cell yields were obtained when these sulfhydryl compounds were supplemented with dithiothreitol, presumable to keep the monothiols in reduced state during long incubation periods. Ascorbic acid could not replace dithiothreitol for this purpose. It is suggested that these carboxylated sulfhydryl compounds play a role in the metabolic activity of M. leprae along with maintaining low redox potential of the medium. PMID- 1870437 TI - Comparison of protective effects with tetra-valent glycolipid antigens and whole cell-inactivated vaccine in experimental infection of Leptospira. AB - The protective antigens (PAgs), glycolipid substance, were extracted from Leptospira interrogans serovars autumnalis, hebdomadis, australis and copenhageni, which were considered as main causal serovars of human leptospirosis in Japan, with chloroform-methanol-water (1:2:0.8, [vol/vol/vol]) solution. The tetra-valent formalin-inactivated leptospiral vaccine (Weil's disease and Akiyami combined vaccine) composed of the four serovars mentioned are used as vaccine to protect human from leptospiral infection in Japan. The protective effect, agglutinating antibody-inducing activity and opsonin-inducing activity of tetra valent PAgs were compared with those of vaccines now in use, which were supplied by two companies, Takeda Chemical Industries, Ltd., and Denka-Seiken Co., in Japan. The tetra-valent PAgs which contained 10 micrograms of each PAg protected hamsters and cyclophosphamide-treated mice from lethal infection of serovar copenhageni and induced agglutinating antibodies against the four serovars in the same degrees as vaccines. These results suggested that the tetra-valent PAgs might be useful as a component vaccine against leptospiral infection instead of formalized whole cells vaccines for human. PMID- 1870439 TI - Role of L3T4+ and Lyt-2+ T cell subsets in protective immune responses of mice against infection with a low or high virulent strain of Toxoplasma gondii. AB - In order to elucidate the role of T cell subsets in protective immunity against infection with high virulent and low virulent strains of Toxoplasma gondii, monoclonal antibodies specific for T cell subsets were injected into mice before immunization or challenge infection. Treatment of mice with monoclonal antibody to either L3T4+ or Lyt-2+ T cells before they were immunized with Toxoplasma cell homogenate prepared from high virulent RH strain tachyzoites markedly reduced survival after mice were challenged with low virulent bradyzoites of the Beverley strain. Thus, induction of protective immunity against bradyzoites of the Beverley strain requires the presence of both L3T4+ and Lyt-2+ T cells. In contrast, mice injected with living bradyzoites of the low virulent Beverley strain after immunization with Toxoplasma cell homogenate acquired protective immunity against high virulent tachyzoites of the RH strain. Lyt-2+ T cells alone appear to be final effector cells for protection against the challenge with high virulent RH strain tachyzoites, since treatment of the bradyzoite-immune mice with anti-Lyt-2 antibody, but not anti-L3T4 antibody, before challenge significantly increased mortality. PMID- 1870440 TI - Macrophage migration inhibitory factor (MIF) produced by a human T cell hybridoma clone. AB - A human T cell hybridoma clone, F5, producing high levels of macrophage migration inhibitory factor (MIF) was established by the emetine-actinomycin D selection method. This clone produced two species of MIF which were separated on a Phenyl Sepharose column. We purified MIF-2 (the more hydrophobic species of the two) to homogeneity from the conditioned medium of stimulated F5 cells by a series of steps that included hydrophobic chromatography, ion-exchange chromatography. Ricinus communis lectin affinity chromatography, and high-performance liquid chromatography on anion exchange and reverse-phase columns. Purified MIF was digested with endoproteinase Lys-C and Asp-N. The amino acid sequences of the generated peptides were determined. No sequence similarity with any other protein was found. The molecular weight of MIF-2 was estimated to be 45 kDa from sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of immunoprecipitates with anti-peptide antibodies. These results show that F5MIF-2 is a novel cytokine. PMID- 1870441 TI - Detection of influenza viruses in throat swab by using polymerase chain reaction. AB - An assay protocol based on exploiting the polymerase chain reaction (PCR) for the direct detection of influenza virus in throat swab is described. By use of the mixture of H1 and H3 primers, it was possible to determine the subtype of the influenza A viruses simultaneously. No visible band was detected after PCR of influenza B or A (H2N2) viruses with a pair of H1 or H3 primers. The dilution experiment showed that the influenza viruses, as few as 1.3-6 plaque-forming units, were sufficient for detecting the HA gene by PCR. All throat swab samples from which influenza viruses had been isolated by conventional method were also positively detected by PCR method. PMID- 1870443 TI - [T-cells in the immune system. 1: Maturation in the thymus]. PMID- 1870442 TI - Heat-killed Salmonella typhi induces the release of prostaglandins and leukotrienes from mouse macrophages. AB - Mouse macrophages pre-labeled with [3H]arachidonic acid (20:4) were shown to release metabolites generated by the lipoxygenase and cyclo-oxygenase pathways following in vitro addition of heat-killed Salmonella typhi. These metabolites were maximally released after 60-90 min of incubation and consisted of prostaglandins (85%), leukotriene C (6%), di-HETEs, leukotrienes D and E (4%), mono-HETEs (2%) and other metabolites (3%). Of the metabolites generated by the cyclo-oxygenase pathway (prostaglandins), 6-keto PGF1 alpha and PGE2 were generated at a ratio of 1.2 to 1. The significance and importance of these results are discussed. PMID- 1870444 TI - [Nutrition in disorders of lipid metabolism]. PMID- 1870445 TI - [Is Agiolax safe in pregnancy and lactation?]. PMID- 1870446 TI - [Which antihypertensive drugs in lithium therapy?]. PMID- 1870447 TI - Characterization of thrombospondin binding to collagen (type I) fibres: role of collagen telopeptides. AB - We have shown that thrombospondin (tsp), like fibronectin (fn) and von Willebrand factor (vWf), exhibits a rapid, specific and saturable binding to collagen type I fibres (from bovine tendon). The level of binding at saturation is very similar to that of vWf. As with fn and vWf, the interaction is ionic in character and appears to occur by a polyvalent mechanism since there is little inhibition of interaction by monomeric collagen. The conformation of tsp, like that of fn and vWf, is important since denaturation causes reduced complexing. Furthermore, conformational changes in tsp due to the presence of Ca++ can modulate the amount of complex formed under physiological conditions. Tsp, like vWf but in contrast to fn, shows little affinity for denatured fibres emphasizing the importance of collagen conformation. Pepsin digestion suggests an important role for collagen telopeptides; vWf- and fn-binding sites are located more within the collagen triple helix. Comparison of the effect on binding after leucine aminopeptidase or carboxypeptidase digestion suggests involvement of the N- rather than C-terminal telopeptides. No evidence was found for a role for fn, the proteoglycan PG2 or collagen type V, which could be present in type I fibres, in mediating the interaction between tsp and the fibres. VWf did not inhibit the interaction of tsp, but fn did slightly when tested in large excess. This suggests separate binding sites in collagen for all three ligands since fn and vWf are also known to bind independently of each other. PMID- 1870449 TI - Fibronectin in healing flexor tendons subjected to immobilization or early controlled passive motion. AB - The medial and lateral forepaw flexor tendons of 20-adult mongrel dogs (n = 40) were transected and repaired with a modified Kessler suture. Post-operatively the dogs were subjected either to immobilization or early controlled passive digital motion. Sacrifices were at 3, 7, 10 and 17 days. The tendons of the contralateral limbs were left intact and used as controls. Urea-heparin-extracted fibronectin was quantitated by competitive ELISA in the tendons and sheaths at the four post injury/repair time periods. In both groups (controlled passive motion and immobilization), fibronectin concentrations were higher in the injured tissues than in control tissues. However, peak fibronectin concentration (7-days post injury/repair) was approximately twice as high in the controlled passive motion tissues as in the immobilized tissues. It was concluded, therefore, that, relative to early controlled passive motion, early immobilization depresses the accumulation of tissue fibronectin during the early stages of healing following injury. PMID- 1870448 TI - The synthesis of a family of structurally related proteoglycans in fibroblasts is differently regulated by TFG-beta. AB - Fibroblasts synthesize a variety of proteoglycans among which is a family of structurally related small proteoglycans, i.e. PG-S1 (biglycan) and PG-S2 (decorin). Fibromodulin, which is present in some tissues as a keratan sulfate proteoglycan, also belongs to this family. We have used primary fibroblasts from fetal skin and bovine sclera in culture to study the metabolism of proteoglycans. In particular the regulatory effect of transforming growth factor-beta (TGF beta), interleukin-1 (IL-1) platelet-derived growth factor (PDGF) and dexamethasone was determined by studies of mRNA levels for these structurally related proteoglycans. Furthermore the synthesis and secretion of these macromolecules was studied using radioactive precursors. TGF-beta induced a 3 fold increase of mRNA for PG-S1, collagen I and III in both types of fibroblasts. mRNA for PG-S2 increased only slightly (1.7-fold) in human skin fibroblasts; while no effect was noticed in sclera fibroblasts. The expression of fibromodulin mRNA was not effected in any of the cells investigated. IL-1, PDGF and dexamethasone had no significant effects on the levels of proteoglycan and collagen mRNA, respectively. Synthesis and secretion of PG-S1, -S2 and fibromodulin wa studied by labeling with [3H]-leucine and [35S]-sulfate. Final separation of PG-S1 and -S2 was achieved by hydrophobic interaction chromatography. TGF-beta induced a 3- to 6-fold increase of [3H]- and [35S] labeled PG-S1; while PG-S2 only increased 1.3- to 1.4-fold in both types of fibroblasts. No effect on synthesis and secretion of immunoprecipitated fibromodulin was noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870450 TI - Effects of growth factors on mucosal scar fibroblasts in culture--a possible role of growth factors in scar formation. AB - Various growth factors are known to play important roles in wound healing, especially in an early inflammatory phase. However, their roles in subsequent scar formation phase are relatively unexplored. The aim of this study is to investigate the mechanisms of regulation in scar formation by these factors. Scar fibroblasts (SF) were obtained from immature scar tissue made at rat hard palate 1 month after excision and normal fibroblasts (NF) were obtained from the palatal mucosa of untreated control animals. SF showed a longer doubling time, and increased level of protein synthesis when compared to NF. Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) stimulated [3H]-thymidine uptake less effectively in SF than in NF. In both cells, transforming growth factor-beta 1 (TGF-beta 1) inhibited EGF-induced stimulation of [3H]-thymidine uptake, but had no effects when it was added alone. TGF-beta 1 increased collagen synthesis more effectively in SF than in NF. These data indicate that the growth factors may play key roles in regulating proliferation and metabolic activity of fibroblasts during scar formation. PMID- 1870451 TI - A discrete helicoid of collagenous fibrils: the cuticle of deep-sea hydrothermal vent worms (Riftia pachyptila). AB - The fibrillar organization of the collagenous cuticle of the hydrothermal vent worm Riftia pachyptila is described. Fibrils in the posterior part of the cuticle are organized in a classical orthogonal plywood consisting of successive layers of fibrils: in this case, fibrils are oriented in only two directions which are orthogonal, as for pogonophoran. Our new data on the plume of Riftia pachyptila show a new type of fibrillar arrangement of the cuticle: 1) three sets of fibrils are arranged in an hexagonal pattern; 2) fibrils in successive plies are rotated by 60 degrees, and the organization of the fibrillar network is interpreted as a discrete helicoid when compared to continuously twisted plywoods; 3) a fourth set of fibrils crosses the hexagonally arranged plies and is oriented perpendicular to the surface of the body. X-ray diffraction studies of the cuticular fibrils reveal a triple helix which is characteristic of collagen molecules. Results obtained by differential scanning calorimetry (DSC) show that the denaturation temperature of the molecule is 54.7 degrees C for Riftia; whereas it is 58.9 degrees C for type I collagen measured under the same conditions. We discuss the origin of this plywood with respect to biomechanical constraints, self assembly processes, and compartmentation of the extracellular space. The involvement of the cell membrane in the fibrillogenesis of collagen is also discussed. PMID- 1870452 TI - Ultrastructural immunolocalization of osteopontin in metaphyseal and cortical bone. AB - The ultrastructural localization of osteopontin in bone was determined especially focussing on the relationship to bone forming cells, i.e. osteoblasts and osteocytes. Thus, rat metaphyseal and cortical bone was fixed in a mixture of low concentration glutar- and paraformaldehyde and embedded at low temperature in Lowicryl K11M. Polyclonal antibodies raised against rat osteopontin fusion protein were incubated on ultrathin sections and protein G coated with 5-nm colloidal gold was used for detection. The results demonstrate most intensive labeling in the mineralization front of newly formed bone; whereas lower concentration of label was found in the osteoid both in metaphyseal and cortical bone. The concentration of marker was substantially higher in newly formed bone near osteoblasts compared to bone constituting the osteocyte lacuna. Intracellularly the prevailing localization of label was to large Golgi vesicles in osteoblasts. Only focally local accumulation of marker was seen at the cell/osteoid surface. The observations suggest a function of osteopontin also in the mineral turnover of newly formed bone. PMID- 1870453 TI - Crimp morphology in the fibre-forming collagens. PMID- 1870454 TI - [What are the expectations for development of a vaccine against AIDS?]. PMID- 1870455 TI - [The effect of 2 thrombocytopoietic-active polypeptides on thrombocytopenia in mice irradiated with ionizing radiation]. AB - The assumption that thrombocytopoietin preparations prepared in our own laboratory can prevent the decrease of the number of thrombocytes in the peripheral blood of animals irradiated by a sublethal dose of gamma-ionizing rays was tested in an experiment on mice. Two preparations were tested: one, with an influence on stem cells, which directs them in the direction of megacariocyte differentiation (Smp), and the other one which is essential for the endomitosis and production of thrombocytes (Stp). The results undoubtedly indicated that a decrease in the number of thrombocytes occurred in the peripheral blood of animals following irradiation without the use of the preparations mentioned above, and was mostly emphasized after 9 days. The fact that was also demonstrated was that this decrease is significantly lesser if the animals are treated, after irradiation, with both preparations together or only with preparation Stp which has an influence on the directed thrombocytopoiesis cells, while the preparation Smp does not show such an effect. On the basis of these results a conclusion was made that thrombocytopenia of irradiated subjects sets on as a consequence of a temporary lack of one of the two poietins of thrombocytopoiesis, meaning Stp, which can be of importance in the treatment of the acute radiation syndrome in man. PMID- 1870456 TI - [The importance of intact parathyroid hormone determination in the evaluation of parathyroid gland function]. AB - The study investigates the importance of determining the intact parathormone in the evaluation of parathyroid gland function in different conditions of change in their function and the alteration of parathormone metabolism: primary and secondary hyperparathyroidism, hypoparathyroidism and hyperthyroidism. The role and place of intact parathormone determination in routine diagnostic schemes of calcium homeostasis disorders was reviewed by the simultaneous determination of the indicators of calcium and bone metabolism and other calcium homeostasis hormone regulators, as well as the C- and N-terminal parathormone fragments and by establishing their mutual links with the values of the intact parathormone. PMID- 1870457 TI - [Lactates in the cerebrospinal fluid in patients with bacterial and viral meningitis--significance in differential diagnosis]. AB - Lactate concentrations were determined in the cerebrospinal fluid of patients with purulent, tuberculous and viral meningitis. The control group consisted of 10 patients with meningism (the presence of the meningeal syndrome with a normal cytobiochemical finding of the cerebrospinal fluid). The enzymatic kinetic method of the firm "Behringer" was used. In all the patients with purulent meningitis lactate values were elevated (above 6.2 mmol/l), and the highest values (above 15.0 mmol.l) were found in the patients who also developed respiratory failure. The lactate values in the cerebrospinal fluid of patients with purulent meningitis were higher in statistical significance than in all other examined groups of patients (p less than 0.01). The lactate values were in correlation with the total number of leukocytes (r = 0.78, p less than 0.01) and with the percent of polimorphonuclear leukocytes in the cerebrospinal fluid (r = 0.80, p less than 0.01). Elevated lactate values (above 2.95) were also found in all the patients who had tuberculous meningitis and statistically they differed significantly from the cerebrospinal fluid values of the patients with viral meningitis and meningism (p less than 0.01). There was no difference in the cerebrospinal fluid lactates of patients with viral meningitis and meningism (p greater than 0.05). Elevated lactate values were also found in 2 patients who had paraneoplastic meningitis and in 3 patients with cerebral cysticercosis and hydrocephalus, but without meningitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870458 TI - [Fatty material in adrenal cortex cells 1 month after contamination with detergent]. AB - The presence of fatty substances: neutral lipids, triglycerides, and phospholipids was detected in the adrenal cortex 30 days after the termination of detergent influence on white laboratory rats. We found that neutral lipids were of increased quantity in the glomerular, fascicular and reticular zone. Triglycerides were present in a greater extent in the entire cortex of animals which were subjected to the influence of detergents. Phospholipids offer an analogue picture: their quantity was increased in all parts of the adrenal cortex in the experimental animals. The described features of the adrenal cortex after detergent influence termination, considering the three groups of fatty substances, undoubtedly indicate the increased activity of the adrenal cortex. PMID- 1870459 TI - [Case report of unilateral congenital choanal atresia]. AB - A case of unilateral inborn choanal atresia was described in a baby of the age of 4 months. The anomaly was solved by the endonasal approach, which the author recommends as the method of choice in the treatment of choanal atresias because it is very simple, safe and easy to conduct. The paper also discusses other operative methods as well as the best time for conducting the intervention. PMID- 1870460 TI - [Cystic teratoma of the neck]. AB - Teratomas of the neck are very rare, and up to now only a small number of cases has been described (10 in adults), while in children it is a more frequent finding (132 described cases). It is judged that up to 4% of all teratomas in children are located in the cervicothyroid region. The paper presents a case of a cystic teratoma of the neck in a male child of 1.5 years of age, which gradually increased in it's size during the course of 12 months prior to operation. The tumor had the dimensions 3.7 x 3.2 x 2.7 cm, it was multicystic, and clinically it gave the impression of a bronchial cyst. Histologically the tumor contained elements of all three primary embryonic germ layers. PMID- 1870461 TI - [Alcohol in pregnancy]. AB - In 1978, an investigation on alcohol consumption by women, before and during pregnancy, was carried out at Clinic for Gynecology and Obstetrics of the Medical Faculty in Novi Sad. This investigation studied 350 women during their stay in the hospital, after delivery and their newborns regarding birth weight, prematurity, stillbirths, operative interventions for delivery (vacuum extraction, Caesarean section, vaginal breech) and hormonal therapy during pregnancy. Ten years later, in 1988, at the same clinic, a similar investigation took place within the framework of the "Drugs and Pregnancy" project of the WHO Regional Bureau for Europe which included the study of 297 women and their newborns (average birth weight and Apgar-score study). Newborns whose mothers had been drinking before and during pregnancy had lower birth weight and length compared to the newborns whose mothers had never consumed alcohol, but these differences are not of statistical significance (X2 = 2.504; X2 = 0.922). There is no statistical significance either in the incidence of prematurity (X2 = 0.461) or in the incidence of operative interventions during delivery (X2 = 0.632). The stillbirth rate was significantly higher with a 4.3% incidence (p less than 0.05) in women consuming alcohol in contrast to the non-alcohol consumption group (0.5%). More women who had been drinking before and during pregnancy had been receiving hormonal therapy during pregnancy (X2 = 8.195 p less than 0.01). Nowadays, more women drink alcohol (60.6%) than ten years ago (48%) (X2 = 13.874 p less than 0.01). Also, nowadays more women drink during pregnancy (47.5%), than in 1978 - 27.7% (X2 = 26.979 p less than 0.01). PMID- 1870462 TI - [Speech behavior of preschool-age children]. AB - The development of speech is closely related to certain psychic functions. Speech behavior reflects the level of cognitive, emotional and contemplative maturity and the linguistic development of the wider environment in which the child is growing up. The sounds of the language and the configuration of words are directly percepted and reproduced with certain principals of semantics and syntax. The developmental speech standards for articulation, the phonetic analysis of words and the acquaintance with the adjective opposite in the preschool age present important information for the evaluation of child maturity. PMID- 1870463 TI - [Steroid receptors and breast carcinoma]. AB - The rate of response of human breast cancer to endocrine therapy depends upon the estrogen receptor ER levels and progesterone receptor PR levels in tumor tissue. About 55% to 60% of all breast cancers have positive estrogen receptors. Higher values of ER are observed in postmenopausal women compared to younger women, and about 45% to 55% of metastatic breast tumors have positive estrogen receptor values. Approximately 60% of ER positive tumors will respond objectively to endocrine therapy, and about 80% of ER positive and PR positive tumors will respond to hormone therapy. Absence of ER in breast tumors seems to correlate well with the increased response to chemotherapy of the patients. The observation that patients whose tumors contained higher ER values, had longer disease free survival than patients with ER negative tumors, led to the use of ER and PR as the prognostic indicators of the disease. Thus, measurement of ER and PR in tumor biopsies gives us important information concerning future treatment and prognosis of the disease. PMID- 1870464 TI - [Growth factors]. PMID- 1870465 TI - [Methodology in studying laterality in developmental neuropsychiatry]. AB - The extent of literature and research dedicated to the laterality of cerebral functions and it's relation towards peripheral laterality gives the impression that this problem is precisely determined to a greater extent. The fact that can be accepted by the examination of literature is that the relation behavior (in the sense of acting)--brain (in the sense of a material determination of behavior itself) cannot be accepted as precisely determined or according to definition, not by nature nor by the mechanism of establishing this relation. From the perspective of the clinical viewpoint of the meaning of left-handedness the most acceptable is the theory of Satz Orsini and Sopper from 1986 in which they consider that non-righthanded people present a heterogenous group with a few individual sub-types: pathological lefthanded persons; ambivalent persons, in other words, ambidexters and the group of lefthanded persons by nature. On the basis of present neuropsychological research and in accordance with the psycho neuro-vegetative approach to the semiotics of the developmental age of Popov et al., a complete battery is given which enables the neuropsychological analysis according to Orzbut's principals. PMID- 1870466 TI - [Prevention of tooth caries using mineral water]. AB - Numerous investigations showed that fluorides play an important role in the prevention of teeth caries, which acts as one of the most widely spread diseases nowdays. Consequently, the bringing in of optimal amounts of fluorides into an organism is of great value for the health of teeth. One of the possible sources of fluorides is mineral water, which brings out the importance of learning about the fluoride concentration in it. Fluoride determination was carried out by the potentiometric method, using the fluoride-selective electrode. Fourteen samples of mineral water from the common market in Novi Sad, were analysed. The results are given in mgF-/L and mumol F-/L. The fluoride concentration above 0.5 mgF-/L has the preventive effect on the health of teeth. From the obtained results it can be concluded that some mineral waters are recommendable as a source of fluorides needed to prevent teeth caries. PMID- 1870467 TI - [Cytochemical study of the thyroid gland]. AB - The paper presents the importance of cytochemical research in the diagnostics of thyroid gland diseases. It is considered that this research usefully supplements the standard cytodiagnostics of the thyroid, especially in clarifying functional and morphological changes in goiter. Given are the basic principals of cytochemical analyses as well as the valuing, in other words, the quantification of cytochemical results. The following methods are more closely described: PAS, alpha-naphthilacetate esterase, naphthol AS-D acetate esterase, peroxidase, beta glucuronidase and alkaline phosphatase. PMID- 1870468 TI - [Treatment strategy in malignant genital tumors in childhood and adolescence]. AB - In the period of 1960-1987 at the Clinic for Gynecology and Obstetrics in Novi Sad 30,398 extensive abdominal and vaginal operations were carried out. In the same lapse of time 59 female patients in their childhood or adolescence were operated on due to an ovarian gland tumor. There were 5 female patients up to the age of 14, and 54 female patients from 14-18 years of age. There were 4 malignant tumors: 2 in childhood age, and 2 in adolescence, and 55 benign ones. By presenting the severeness of the diagnosis (the rarity of the tumor) and the complete treatment strategy, the authors state the principals which should be observed with operations on the genitals of children and adolescents: operation is the method of choice; these cases should be operated on in great medical centers; "ex tempore" biopsy is necessary. The extent of the operative procedure presents a delicate problem, because great care should be taken about the endocrine function of the ovary, the somatic development, menstrual and reproductive function, potential malignancy, and possible relapse, so the authors speak in favor of relaparotomy and radicalization of the first procedure rather than in favor of a great radicalization in the first act. Depending on the nature of the tumor, postoperative irradiation or chemotherapy is recommended. In prevention, regarding early diagnosis, the opening of school dispensaries for childhood and adolescent gynecology is recommended, as well as vaginoscopic examination and the interdisciplinary work of the gynecologist, the surgeon for children and the pediatrician. PMID- 1870469 TI - [Health aspects of air quality]. AB - The pollution of air is one of the most pressing public service problems resulting from the process of urbanization, industrialization and traffic expansion. Air quality control is carried out continually with the aim of assessing the situation and proposing prophylaxis measures. Our investigations focussed on air sediment, soot and sulphur dioxide. With regard to engine exhaust gases, the paper presents the concentration data for carbon monoxide, nitrogen oxides and lead. Our findings point to a significant presence of all the parameters investigated, which is in accordance with the findings of other authors. The quantities of lead determined in the air give rise to special concern, classifying the air into the second or even, third quality class. Bearing the problem of chronic plumbism in mind, this pollutant is a serious health risk for all citizens, especially younger ones. It is present both directly in the air we breathe and indirectly, since lead residues were discovered in the plants growing along major motorways in the range of up to 200 m. The concentrations of soot also had an increasing tendency in the heating season, classifying the air into the third quality class. The quantities of other air quality indicators, such as sulphur dioxide, nitrogen oxides, carbon monoxide and air sediment ranged within the limits allowed. In addition, an increasing tendency was observed both for acute and chronic diseases in the morbidity rate of adults living in Novi Sad and Vojvodina. In order to prevent air pollution and its detrimental effects to human health it is necessary to relocate the polluting facilities, analyze all the factors or urban life and the technological problems involved. PMID- 1870470 TI - [Frequency of congenital anomalies in neonates in Bosanska Krajina (1985-1988)]. AB - The following can be stated on the basis of an incidence analysis of the results of birth defects in the sample of newborn infants of Bosanska krajina (1981-1985) and their distribution in the observed sample and infants' sex: In the analysed sample of newborn infants of Bosanska krajina (N = 40,450) there were 1454 newborn infants with birth defects--1375 with one and 79 with multiple defects (every 28th newborn), out of which there were 1344 full-term, 98 premature and 12 stillborn infants. The relative incidence of birth defects in the analysed sample of newborns of Bosanska krajina (3.57%) and its subsamples (full-term 3.53%; premature 14.55%; and stillborn 2.55%) coincides with the variation range registered in the samples of Yugoslav and world populations. Significant differences in the incidence of birth defects with respect to the "status" of the newborn occur in comparisons of subsamples of full-term and premature infants (0.01 greater than p greater than 0.001) and the premature and total observed sample of newborns of Bosanska krajina (p less than 0.001). The incidence analysis by newborns' sex shows significant differences in the incidence of defects between female and male newborns (p less than 0.001). PMID- 1870471 TI - [An article on alcoholism from 1827. Dr. Jovan Stejic: Inebriation]. AB - In 1827 Dr Jovan Stejic (1803-1853) published an article under the title Inebriation in the Chronicle of the Serbian Registry. In the article, in a very picturesque manner, he gives his views on the causes and consequences of alcoholism, as well as the way of it's treatment. PMID- 1870472 TI - [Immunity against tetanus 3 years after revaccination]. PMID- 1870473 TI - Residency training for medical physicists. PMID- 1870474 TI - A numerical investigation of the dependence of NMR signal from pulsatile blood flow in CINE pulse sequences. AB - The Bloch equations have been solved using numerical techniques for a uniform fluid undergoing periodic pulsatile flow in an NMR imaging experiment. The magnetization and NMR signal have been calculated for experimental parameters appropriate for a CINE sequence (TR = 40 ms, (TE = 14 ms) applied to the study of pulsatile aortic or other arterial flows. The flow velocity profile is obtained by Fourier superposition of different harmonics and it is shown that the steady state NMR signal has reduced high-frequency components. There is also a time delay between peak signal intensity and flow because the backflow effects that can be as much as 100 ms. The apparent pulsatility depends on the NMR sequence parameters. Some limitations of the phase contrast flow-imaging method are also discussed for nonuniform flow. PMID- 1870475 TI - Localized in vivo high-resolution NMR imaging using gradient subencoding technique. AB - A new spatial localization technique for in vivo high-resolution imaging is presented here. In contrast to other localization techniques that use a series of rf pulses to define a volume of interest, only one rf pulse is utilized in the proposed method for selection of a region to be imaged. Instead of rf pulses for region selection, subencoding gradient pulses are used for the localization together with a convolution process on each phase-encoding gradient by a set of additional gradients (e.g., y direction). Then the 2-D localization is completed by restricting the bandwidth in the readout direction (e.g., x direction). The latter is simply achieved by using a low-pass filter in the receiver system. By applying this technique on a human body, localized in vivo high-resolution images are obtained for the knee with much improved resolution. 100 x 100 microns in plane (x,y plane) resolution images obtained from the human knee demonstrate that localized in vivo high-resolution imaging for both human and animals is possible with an in-plane resolution of below 100 microns. PMID- 1870477 TI - The determination of the contrast necessary for the detection of small positive or negative contrasting areas in flood field images by employing ROCs. AB - Flood field images are acquired and inspected visually during weekly quality control procedures for scintillation cameras. Nonuniformities are quantified by parameters such as integral and differential uniformity (IU and DU). This study is a first step toward understanding the relation between the standard quantitative parameters measured in regular quality control procedures and the performance of clinicians in the interpretation of studies conducted with the same scintillation camera. This study quantified the performance of observers to detect nonuniformities in an ideal case. Flood field images (64 x 64) were simulated on a computer. One contrasting area (2 x 2) was superimposed at random positions on each image. Positive and negative contrast values of 10%, 8%, 6%, 4%, 2%, and 0% were employed. The linearly scaled computer images were transferred to film. These films were evaluated by 11 observers to obtain receiver operating characteristic (ROC) curves. The areas (A) below the average ROCs for every contrast value were utilized as an indication of the detectability of the contrasting areas superimposed on the flood images. The results indicate areas with positive contrasts greater than 6% and negative contrasts less than 8% were detected with 95% probability (A greater than or equal to 0.95). These contrasts correspond to optical density differences of greater than 0.051 and less than -0.072, respectively (assuming a gamma, G, or gradient of 2.0 for the x ray film characteristic curve). The contrast values and optical density differences obtained may serve as guide values, beyond which action must be taken to correct the scintillation camera nonuniformity to ensure optimum imaging. These results can be utilized by other institutions to predict the threshold contrasts of their imaging systems if G can be measured or estimated for the systems. PMID- 1870476 TI - Quantitative imaging of I-124 using positron emission tomography with applications to radioimmunodiagnosis and radioimmunotherapy. AB - Positron emission tomography (PET) is potentially useful for the quantitative imaging of radiolabeled antibodies, leading in turn to improved dosimetry in radioimmunotherapy. Iodine-124 is a positron-emitting nuclide with appropriate chemical properties and half-life (4.2 days) for such studies since the radiolabeling of antibodies with iodine is well understood and the half-life permits measurements over several days. Unfortunately, I-124 has a complex decay scheme with many high-energy gamma rays and a positron abundance of only 25%. It has therefore been largely ignored as a PET-imaging nuclide. However, measurements made with phantoms and animals under realistic conditions using a BGO-based PET scanner have shown that satisfactory imaging and quantitation can be achieved. Investigations of spatial resolution, the linearity of regional observed count rate versus activity in the presence of other activity, and the visualization and quantitation of activity in spheres with different surrounding background activities were carried out with phantoms up to 22 cm in diameter. Compared with F-18, spatial resolution was only slightly degraded (13.5 mm FWHM vs 12 mm FWHM) while linearity was the same over a 10:1 activity range (0.015 to 0.15 MBq/ml for I-124). The visualization and quantitation of spheres was also slightly degraded when using similar imaging times. Increasing the imaging time for I-124 reduced the difference. To verify that the technique would work in vivo, measurements were made of human neuroblastoma tumors in rats which had been injected with I-124 labeled 3F8 antibody. Although the number of samples was small, good agreement was achieved between image-based measurements and direct measurements of excised 4-g tumors. Thus quantitative imaging of I-124 labeled antibodies appears to be possible under realistic conditions. PMID- 1870478 TI - Comparison of NaI(Tl), CdTe, and HgI2 surgical probes: physical characterization. AB - The physical properties of three surgical probes containing different radiation detectors are compared: a NaI(Tl) scintillator with a flexible, fiber-optic light guide, and two semiconductor detectors that operate at room temperature, CdTe and HgI2. Also compared are spectra, energy resolutions, and counting efficiencies measured at a variety of gamma-ray energies between 30 and 1000 keV. The energy resolution of the NaI probe is substantially poorer than that of either semiconductor probe due in part to light losses in coupling the scintillator to the fiber optics. The semiconductor probes have complex spectral response due to charge-carrier trapping and K x-ray escape, and not all photoelectric interactions in these detectors contribute to the useful part of the photopeak. Above 120 keV the counting efficiency for the NaI probe is an order of magnitude higher than for the CdTe and HgI2 probes. Both energy resolution and counting efficiency are slightly better for the HgI2 probe than for the CdTe probe. PMID- 1870480 TI - The effects of different correction techniques on absolute volume determination with SPECT using a threshold edge detection method. AB - Quantitation of planar radionuclide images is hampered by structures containing radioactivity which overlie or underlie the organ of interest. The introduction of single photon emission computerized tomography (SPECT) overcame this problem to a large extent and enhanced the contrast of the images. Attenuation of photons, however, degrades the resultant SPECT images and correction methods for photon absorption and scatter were subsequently proposed. The different correction methods have variable effects on the reconstructed images. If threshold techniques are used to quantitate organ volume, i.e., combining pixels with the same percentage of the maximum pixel count in the volume, the selected threshold values which give the most accurate volume determination, will be affected by the specific correction method used. In this study, the effect of various SPECT image correction methods on threshold was investigated. A thorax phantom containing volumes ranging from 30 to 1200 ml was used. Threshold values varying from 45.6% (210 ml without any correction) to 23.7% (1200 ml with a combination of scatter subtraction and attenuation correction) were used to produce correct quantitation when different methods were investigated. A negative correlation was found between threshold and volume. This reduction in threshold was most prominent when scatter and attenuation correction were combined. This study shows that correction methods for attenuation of photons influence the threshold value for volume quantitation and the use of a constant threshold value could lead to underestimation of larger volumes. PMID- 1870479 TI - Comparison of NaI(T1), CdTe, and HgI2 surgical probes: effect of scatter compensation on probe performance. AB - Spatial variation in the background source distribution makes tumor detection difficult for single-detector probes. Using a single energy window that brackets the photopeak helps discriminate against background events dominated by Compton scattering. Another approach is to use the information provided by an additional window in the Compton region. The performances of NaI(T1), CdTe, and HgI2 surgical probes have been compared under realistic simulations of a tumor-staging procedure using optimal single-sided energy windows and a two-window scatter subtraction technique. Results showed that despite the differences in energy resolution of the detectors, the performances of the probes in a variable background were similar when optimal single energy windows were used. When the background variations were large, using information provided by a second window improved probe performance. PMID- 1870481 TI - Simultaneous reconstruction, segmentation, and edge enhancement of relatively piecewise continuous images with intensity-level information. AB - A multinomial image model is proposed which uses intensity-level information for reconstruction of contiguous image regions. The intensity-level information assumes that image intensities are relatively constant within contiguous regions over the image-pixel array and that intensity levels of these regions are determined either empirically or theoretically by information criteria. These conditions may be valid, for example, for cardiac blood-pool imaging, where the intensity levels (or radionuclide activities) of myocardium, blood-pool, and background regions are distinct and the activities within each region of muscle, blood, or background are relatively uniform. To test the model, a mathematical phantom over a 64 x 64 array was constructed. The phantom had three contiguous regions. Each region had a different intensity level. Measurements from the phantom were simulated using an emission-tomography geometry. Fifty projections were generated over 180 degrees, with 64 equally spaced parallel rays per projection. Projection data were randomized to contain Poisson noise. Image reconstructions were performed using an iterative maximum a posteriori probability procedure. The contiguous regions corresponding to the three intensity levels were automatically segmented. Simultaneously, the edges of the regions were sharpened. Noise in the reconstructed images was significantly suppressed. Convergence of the iterative procedure to the phantom was observed. Compared with maximum likelihood and filtered-backprojection approaches, the results obtained using the maximum a posteriori probability with the intensity level information demonstrated qualitative and quantitative improvement in localizing the regions of varying intensities. PMID- 1870482 TI - Molybdenum target x-ray spectra: a semiempirical model. AB - A semiempirical model for generating molybdenum target x-ray spectra is presented. The model is an extension of a previous model developed by the authors for tungsten and takes into account the depth of production for both bremsstrahlung and characteristic x-ray photons. As in the previous work, the optimal model parameters were determined using nonlinear least-squares fits to experimental data. Good agreement between the two was obtained. By varying target angle, off-axis angle, and filtration in the model in accordance with the x-ray tube and geometry of interest, results consistent with tabulated spectra for different conditions have been obtained. PMID- 1870483 TI - Quantitative scatter measurement in digital radiography using a photostimulable phosphor imaging system. AB - X-ray scatter fractions measured with two detectors are compared: a photostimulable phosphor system (PSP) and a conventional film-screen technique. For both detection methods, a beam-stop technique was used to estimate the scatter fraction in polystyrene phantoms. These scatter fraction measurements are compared to previously reported film-based measurements. Scatter fractions obtained with the PSP were in good agreement both with measurements using film as well as with most previously reported measurements. For the PSP measurements, repeatability was better than 1%. It was found that the PSP provides a precise x ray detector for quantitative scatter measurement in digital radiography. PMID- 1870484 TI - Comparison of imaging properties of a computed radiography system and screen-film systems. AB - To compare the diagnostic quality of images obtained with a computed radiography (CR) system based on storage phosphor technology with that obtained with conventional screen-film systems, a dual-image recording technique was devised. With this technique, a CR imaging plate is placed behind a screen-film system in a conventional cassette. This makes it possible to obtain two images simultaneously, one from each system, in a clinical examination with the same patient positioning, the same degree of patient motion, the same geometric unsharpness, and no additional exposure. The modulation transfer functions (MTFs) of the CR system with and without the dual-image recording technique were greater at low frequencies, but lower at high frequencies, that the MTFs of the screen film systems used. The noise Wiener spectra of the CR images at the plane of the imaging plate were greater than those of the screen-film systems, but were comparable to those of the screen-film systems at the plane of the printed film due to the reduction in image size. Clinical chest images obtained with the dual image recording technique appeared comparable, probably because of the image size reduction and the use of mild unsharp mask processing. PMID- 1870485 TI - X-ray imaging using amorphous selenium: a photoinduced discharge readout method for digital mammography. AB - A new digital image readout method for electrostatic charge images on photoconductive plates is described. The method can be used to read out images on selenium plates similar to those used in xeromammography. The readout method, called the air-gap photoinduced discharge method (PID), discharges the latent image pixel by pixel and measures the charge. The PID readout method, like electrometer methods, is linear. However, the PID method permits much better resolution than scanning electrometers while maintaining quantum limited performance at high radiation exposure levels. Thus the air-gap PID method appears to be uniquely superior for high-resolution digital imaging tasks such as mammography. PMID- 1870486 TI - Use of storage phosphor imaging plates in portal imaging and high-energy radiography: the intensifying effect of metallic screens on the sensitivity. AB - The sensitivity of storage phosphor imaging plates (SPIP) at megavolt photon energies (60Co, 6-, 10-, and 18-MV radiotherapy beams) is studied both experimentally and by Monte Carlo radiation transport calculations. In addition, the same techniques are used to investigate the intensifying effect of metal screens on the sensitivity of the SPIP. The results provide evidence that the sensitivity of the SPIPs is proportional to the absorbed energy in the phosphor layer per cGy. The spectral sensitivity is calculated for photon energies between 10 keV and 20 MeV for various SPIP-screen combinations. PMID- 1870487 TI - Clinical implementation of AAPM Task Group 32 recommendations on brachytherapy source strength specification. AB - Historically the strength of sealed brachytherapy sources has been described by many physical quantities, including true activity, apparent activity, and equivalent mass of radium. Recently, the AAPM Task Group 32 recommended that these quantities be replaced by a single quantity, air-kerma strength, with units of muGy m2h-1. A set of equations has been developed for unambiguously converting source strength estimates and renormalizing published dose-rate tables, which assume traditional quantities and units, into forms consistent with air-kerma strength. For commonly used brachytherapy sources, multiplicative conversion factors for each source-strength formalism and set of units are given. To convert equivalent mass of radium to air-kerma strength requires a single multiplicative factor, 7.23 muGy m2h-1/mgRaEq, applicable to all sources. Based upon a review of vendor source specification practices, the factors for converting source strength of 198Au, 103Pd, and 125I seeds from apparent mCi to air-kerma strength are 2.06, 1.29, and 1.27 muGy m2h-1/mCi(apparent), respectively. These factors are independent of source geometry but depend on the nominal exposure rate constant value selected by the vendor. Conversion factors applicable to mass of radium or true activity depend upon both source geometry and radionuclide identity. Because many of these conversion factors depend upon vendor choices of physical constants and exposure rate constants, readers are cautioned to carefully review vendor source strength specification practices before adopting these values clinically. Finally, the relationships between the various source strength quantities and absorbed dose rate in the medium surrounding the source are elucidated. PMID- 1870488 TI - Thermoluminescent dosimetry for 103Pd seeds (model 200) in solid water phantom. AB - Dose measurements using LiF thermoluminescent dosimeters (TLD) have been performed for single 103Pd seeds (model 200) at the center of a solid water phantom. TLD cubes 1 mm on an edge were used for measurements from 1 mm to 1 cm at 1-mm intervals. The cubes were centered along transverse and longitudinal axes and along radial lines from seed center at 10 degrees increments. TLD chips of dimension 3.1 X 3.1 X 0.89 mm were used at distances of 2, 2.5, 3, and 4 cm at 15 degrees angular intervals. Data are presented as the product of distance squared and dose rate per unit source strength, plotted versus distance and angle. At 1 cm from seed center along the transverse axis this product was found to be 0.88 cGy cm2 mCi-1h-1. A dose-rate table in polar coordinates has been formulated for use with multiseed dose distribution calculations. Comparison with data of Meigooni et al. [Endocuriether./Hyperthermia Oncol. 6, 107-117 (1990)] shows general agreement for distances of 2 cm or greater. A comparison of our transverse axis data with Russell's calculated values (Theragenics Internal Report, 4 November 1984) for an ideal point source of 103Pd shows very good agreement except at distances less than 0.5 cm, where differences are attributable to the extended source effect in the actual seed. PMID- 1870489 TI - A new method for characterizing beta-ray ophthalmic applicator sources. AB - A technique is described which enables one to obtain detailed dose characteristics of 90Sr beta-ray ophthalmic applicators. A radiochromic radiation detector which is a solid-state solution of hexahydroxyethyl pararosaniline cyanide in a nylon polymer (i.e., thin foil), has been used to determine the surface dose rate and dose distribution of these sources. The detectors are rugged, easily handled, have an equivalent response (optical density per unit absorbed dose) to photons and electrons, and produce high-resolution images. They have been found useful for this application due to the high surface dose rates [0.10-1.0 Gy (H2O)/s] and their low sensitivity (approximately 10(4) Gy for an optical density of 1.0). The foils have been evaluated on a He-Ne scanning laser densitometer with a resolution of 0.3 mum. Comparison with NIST (formerly NBS) extrapolation ionization chamber measurements indicates surface dose-rate agreement within 6%. Spectral dosimetric characteristics are presented and discussed. PMID- 1870490 TI - Calibration of 192Ir high-dose-rate afterloading systems. AB - A method is described for calibration of 192Ir high-dose-rate (HDR) brachytherapy afterloading systems. Since NIST does not offer calibration of ionization chambers with the gamma-ray spectrum of iridium-192, an interpolation procedure is employed, using calibrations above (137Cs, 662 keV) and below (250 kVcp, 146 keV x rays) the exposure-weighted average 192Ir energy of 397 keV. The same total wall + cap thickness must be used for both calibrations, and for the 192Ir measurements. A wall + cap thickness of 0.3 g/cm2 is recommended to assure charged particle equilibrium and to exclude secondary electrons emitted from the source encapsulation. Procedures are described for determining the corrections for source-chamber distance and room scatter during the source calibration in inverse-square-law geometry. A new well-type ionization chamber has been designed specifically for convenient routine use with the HDR afterloading system. It can be calibrated by means of a previously calibrated 192Ir source, and offers a simple means for verifying the decay rate and for calibrating 192Ir replacement sources. PMID- 1870491 TI - Superposition on a multicomputer system. AB - Superposition (convolution using a noninvariant kernel) has been shown to be a highly promising technique for use in calculating dose distributions in radiotherapy treatment planning. However, one major difficulty that currently prevents use in routine planning is the computational effort required to perform the calculation in three dimensions. To help solve this problem the superposition technique has been implemented on a parallel processor multicomputer in order to examine the performance characteristics of such a system. Up to eight elements have been connected in a pipeline (linear array), and tree networks of three and seven processors have also been constructed (using INMOS T800 transputers). The significant results obtained with these networks are: (1) Both topologies provide near-linear speedup with increasing processor number (8 processors provide 7.81 times the computing power of a single processor when using an optimal communication packet size); (2) increasing communication packet size from 1 voxel to an optimum of approximately 40 voxels significantly reduces communication overhead per processor. Overhead per processor for a 7-element linear array is 6.9% when using 1-voxel packets, but only 1.8% when using 40-voxel packets; (3) the topology of the network has some effect on communication overhead: Arranging 7 processors in a 1-2-4 binary tree reduces overhead to 80.1% of that encountered using a 7-element linear array (with packet size of 1 voxel). PMID- 1870492 TI - 3-D dose-volume compensation using nonlinear least-squares regression technique. AB - A method for external beam dose-volume optimization is presented. The Gauss Marquardt nonlinear least-squares regression technique is applied to compensator design and determination. The dose distribution (uniform or otherwise) desired throughout a volume is specified. Compensators optimized to produce the necessary variation of beam intensity across the surface of each beam are simultaneously determined for all the beams. Solutions for homogeneous dose, homogeneous target dose, and restricted dose to exterior target volume structures, and inhomogeneous target dose cases are presented. Dependence of the results on the number of parameters as well as the role of degree of desirability weighting is explained and illustrated via examples. Discussion of the significance and limitations of this optimization method is also presented. PMID- 1870493 TI - Extra lethal damage due to residual incompletely repaired sublethal damage in hyperfractionated and continuous radiation treatment. AB - In the conventional linear-quadratic model of single-dose response, the alpha and beta terms reflect lethal damage created during the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with "unconventional" treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD. The expressions developed by Thames [Int. J. Radiat. Biol. 47, 319 339 (1987)] for fractionated treatment (the IR model) and by Dale [Br. J. Radiol. 58, 515-528 (1985); 59, 919-927 (1986)] for protracted and fractionated treatment are found to be similar to our results in the limiting case where the pool of SLD is very large (infinite).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870495 TI - Induced effects in ionization chamber cables by photon and electron irradiation. AB - Photon and electron irradiation effects in cables and connectors of ionization chambers were investigated under different experimental conditions by means of measurements of the chamber response to a 90Sr standard check source and by measurements of radiation-induced leakage current. Correction factors for irradiation effects on cables and connectors were obtained as a function of the radiation energy, cable length, and absorbed dose dependences. PMID- 1870494 TI - Bremsstrahlung review: an analysis of the Schiff spectrum. AB - A concise approximate formula computed by Schiff for the intensity spectrum of bremsstrahlung photons has been a valuable starting point for many medical physics applications, including the Task Group 21 protocols. This paper provides a brief review of the literature related to determination of the bremsstrahlung spectrum and to the Schiff formula in particular. It describes the approximations Schiff made to obtain this formula, including the Born approximation, and the exponential nuclear screening potential, the infinite-mass nucleus approximation, and the "extreme relativistic" approximation. A derivation of a more exact formula that avoids the last of these approximations is presented. This provides a check on the accuracy of the Schiff spectrum for linear accelerator energies used clinically. Comparisons with the Schiff thin-target result are presented. A thick-target bremsstrahlung spectrum is calculated and compared with the forward spectrum obtained from Monte Carlo simulations of the x-ray production in two linear accelerator treatment heads. PMID- 1870496 TI - Measurement of accelerator bremsstrahlung spectra with a high-efficiency Ge detector. AB - A Compton spectrometer with a high-efficiency Ge detector was used to measure photon spectra from clinical accelerators. The response-function matrix for the detector system was determined using ten radioactive sources that emitted gamma rays of single energy ranging from 279-1525 keV. The system was tested by measuring the spectrum from a 60Co teletherapy machine. The energy distribution of tungsten target bremsstrahlung produced by 2.2, 2.5, 15, 20, and 25 MeV electrons in two clinical accelerators were determined. Theoretical thin-target calculations overestimate the number of photons in the high-energy regions of the spectra, as was expected. However, theoretical thick-target calculations underestimate the numbers of high-energy photons. PMID- 1870497 TI - Effect of tissue inhomogeneity on dose distribution of continuous activity of low energy electrons in bone marrow cavities with different topologies. AB - Monte Carlo calculations have previously been performed by Eckerman to evaluate the absorbed fractions of continuous sources of monoenergetic electrons in marrow cavities of human bone. The difference in scattering power of electrons in cortical bone (CB) and the red marrow (RM) was neglected. In the present work the Integrated Tiger Series and Electron-Gamma-Shower Monte Carlo codes were used to investigate the effect of topology of the bone and bone marrow interface on backscatter dose increase to the marrow. Planar, cylindrical, and spherical geometries were included. For the planar geometry, a maximum dose increase of 9 +/- 1 (S.E. of the mean) % was obtained in the region within 12 mg/cm2 from the interface due to a semi-infinite source of electrons with energy greater than 0.5 MeV. An increase of 7 +/- 1% was observed experimentally in the same region due to a semi-infinite source of 32P. This was in good agreement with Monte Carlo calculation. Averaged over the region of RM embedding electron sources between two planar CB/RM interfaces 1000 microns apart, a dose enhancement of 10 +/- 2% was predicted for electron energies from 1 to 1.75 MeV. For the cylindrical interface with 500-microns radius of curvature, the maximum dose increase averaged over the whole cylinder due to an isotropic distribution of monoenergetic electrons inside the cylinder was 12 +/- 1%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870498 TI - Automated data collection and analysis system for MOSFET radiation detectors. AB - Metal oxide semiconductor field effect transistors (MOSFET) have been used as radiation dosimeters. Because of their small detector size, minimal power requirements, and signal integration characteristics, they offer unique possibilities as real-time dose monitors in radiotherapy. An automated data collection and analysis system for use with MOSFET radiation dosimeters has been designed and built. The objective was to design a system which can acquire and process the MOSFET signals in real time, in any radiation field encountered in radiotherapy. In particular, major problems have been solved arising from the intrinsic drifts of the MOSFET signal during low dose rate measurements. These signal drifts are significant when the MOSFET detector is used in applications such as on-line monitoring of radiation dose delivery in brachytherapy or radioimmunotherapy. The data collection and analysis system includes a portable IBM-compatible personal computer fitted with digital-to-analog and analog-to digital converter boards. A single-chip programmable current supply is used to power the MOSFET dosimeters. Intrinsic and extrinsic drifts in signal due to ion diffusion and electron tunneling are corrected by deconvolution of the collected data in real time or after data collection. The data acquisition system and signal-processing methodologies are described. PMID- 1870499 TI - Low-contrast focal lesion detectability phantom for 1H MR imaging. AB - A phantom made from tissue-mimicking materials is reported for testing 1H MRI systems regarding their ability to detect small low-contrast focal lesions and to delineate the boundaries of larger lesions. Two sets of seven spherical simulated lesions with diameters of 2, 3, 4, 5, 6.3, 7.9, and 9.5 mm have T1 and T2 values somewhat higher than the corresponding values in the surrounding simulated normal tissue. Relaxometer determinations of T1 and T2 for the simulated normal tissue yielded 955 and 106 ms, respectively, at 22 degrees C and 1 T. The corresponding values in set #1 of the simulated lesions were 1017 and 175 ms and in set #2 were 1002 and 127 ms. These T1 and T2 values are similar to those for brain and brain lesions but are too high to represent soft tissue such as liver and muscle. The centers of the 14 lesions are coplanar, and eight alignment devices surround them facilitating superposition of the scan plane and the plane containing the centers of the lesions. Illustrative images made with a 1.5-T system are shown. All simulated lesions are detectable in T2-weighted head coil images. Corresponding T1-weighted images are also shown, the 2- and 3-mm lesions of set #2 and the 2-mm lesion of set #1 not being detectable. The phantoms could be useful for performance or acceptance testing and perhaps for quality assurance testing. PMID- 1870500 TI - Obtaining S values for rectangular-solid tumors inside rectangular-solid host organs. AB - A method is described for obtaining S values between a tumor and its host organ for use with the MIRD formalism. It applies the point-source specific absorbed fractions for an infinite water medium, tabulated by Berger, to a rectangular solid of arbitrary dimensions which contains a rectangular tumor of arbitrary dimensions. Contributions from pairs of source and target volume elements are summed for the S values between the tumor and itself, between the remaining healthy host organ and itself, and between the tumor and the remaining healthy host organ, with the reciprocity theorem assumed for the last. This method labeled MTUMOR, is interfaced with the widely used MIRDOSE program which incorporates the MIRD formalism. An example is calculated. PMID- 1870501 TI - Count-based monitoring of Anger-camera spectra--local energy shifts due to rotation. AB - This study reports on a spectral monitoring method in which (1) a small source fixed to the camera is used, (2) a narrow, offset window is set on the side of the photopeak, and (3) variations in count rate are measured to assess energy shifts in the vicinity of the source. For one camera model, the count rate drops from 100% to 76% over a rotation of 180 degrees, implying a local energy shift of 1.4 keV. Also looked for are local count-rate variations with rotation for (1) wide-symmetric, (2) 20%-symmetric, and (3) 10%-asymmetric windows. The last is in limited use to partially compensate for Compton scattering. The effects of background and time stability are assessed. PMID- 1870502 TI - [Myopathy with lipid accumulation and type-II glutaric aciduria]. PMID- 1870503 TI - [Electromyographic aspects of metabolic myopathies]. PMID- 1870504 TI - [Kearns-Sayre and Melas syndromes]. PMID- 1870505 TI - [Clinical aspects of hereditary peroxisomal disorders]. PMID- 1870506 TI - [Neuroendocrine changes in adrenoleukodystrophy (ALD). Their relationship with new therapeutic strategies]. PMID- 1870507 TI - [Diet therapy with erucic acid in patients with X-linked adrenoleukodystrophy]. PMID- 1870508 TI - [Diagnostic approach to peroxisomal diseases]. PMID- 1870509 TI - [Mental retardation. The nosographic picture of mental retardation]. PMID- 1870510 TI - [Neuropsychology of deficient development]. PMID- 1870511 TI - [Epidemiology and classification of mild mental retardation]. PMID- 1870513 TI - [Psycho-pedagogic aspects of mental retardation]. PMID- 1870512 TI - [Affective processes and the development of thinking]. PMID- 1870514 TI - [Learning in epileptic subjects]. PMID- 1870515 TI - [Early auditory evoked potentials in neuropediatrics]. PMID- 1870516 TI - [Early echographic diagnosis of neonatal cerebral pathology]. PMID- 1870517 TI - [The assessment of coma in childhood]. PMID- 1870518 TI - [Early detection of cognitive disabilities in children with idiopathic epilepsy]. PMID- 1870519 TI - [Epilepsy, endocranial calcifications, celiac disease. An association perhaps no longer accidental]. PMID- 1870520 TI - [Endocranial calcifications. Diagnostic procedure]. PMID- 1870521 TI - [Early diagnosis of mental retardation]. PMID- 1870522 TI - [Indicators of cerebral damage in full-term newborn infants]. PMID- 1870523 TI - [Usefulness of a video collection in a pediatric neurology center]. PMID- 1870524 TI - [Epilepsy and neuropsychological functions]. PMID- 1870525 TI - [Italian Society of Neuropediatrics, 16th national congress. Muscular diseases and mental retardation. Genoa, October 25, 26, 27, 1990. Proceedings]. PMID- 1870526 TI - [The clinical picture of neuromuscular diseases]. PMID- 1870527 TI - [Identification of the dystrophin gene deletions in DMD/BMD patients. Analysis of the reading frame shift and germinal mosaicism]. PMID- 1870529 TI - [Congenital myopathies]. PMID- 1870528 TI - [Clinical,manifestations of the myopathies due to deletions/mutations of the dystrophin gene]. PMID- 1870530 TI - [Metabolic myopathies]. PMID- 1870531 TI - [The defect in muscular glucose-6-phosphate dehydrogenase]. PMID- 1870532 TI - [Encephalomyopathy due to a beta oxidation deficiency. Report of a new case]. PMID- 1870533 TI - [Glycogenosis II. The author's experience with Pompe's disease]. PMID- 1870534 TI - [Changes in the latest RDA for childhood]. PMID- 1870535 TI - [The usefulness of measuring fructosamine in the cord blood of the newborn infants of diabetic mothers]. AB - The aim of our study was to evaluate the usefulness of fructosamine measurement (Fram) in cord blood as an index of glucose metabolism in the last week of pregnancy in infants of diabetic mothers. In newborns and their respective mothers Fram values were surprisingly greater in N than in IDM and IGDM and neonatal and maternal values appeared to be strictly related. While intrauterine growth was associated with metabolic control indexes of 2nd and 3rd trimester gestation. Fram value appeared positively correlated to cord insulin. In conclusion Fram level appears as a good index of glucose metabolic control of the last week of pregnancy and it is associated to cord insulin level and to neonatal hypoglycemia. PMID- 1870536 TI - [A clinical and cytogenetic study of 50 women with Turner's syndrome. Considerations of the problem of pregnancies in these patients. Part 2]. AB - The results of a study on 50 patients with Turner syndrome, all of them older than 14 years and never treated, are reported. In order to correlate karyotypes and clinical manifestations of the syndrome, we performed a complete physical examination and ultra sonographic tests of the heart, kidneys, uterus and ovaries. We found a better spontaneous growth and sexual maturation in mosaic 45.X/46.XX patients than in patients with 45.X and X structural anomalies. No differences were found in heart and kidney congenital anomalies between groups of patients with different karyotypes. We conclude that the presence of an XX-line has an ameliorating effect on height and gonadal function of patients with Turner syndrome. PMID- 1870537 TI - [Anti-Chlamydia psittaci antibodies in a healthy pediatric population]. AB - Psittacosis or ornithosis is a bird disease caused by Chlamydia psittaci which can be transmitted to man. Little is known of the epidemiology of the disease in this region, but occasional cases which have been brought to the authors' attention have prompted an epidemiological study on the subject. The preliminary results indicate a surprising percentage, over 8%, of antibodies in infants and children. This percentage varies little in relation to place of residence, rural or urban, or the presence of animals, but confirms the high risk in parrot-owning households where anti-Chlamydia antibodies are found in 37.5% of children. PMID- 1870539 TI - [Diagnostic considerations in "constitutional bone diseases"]. AB - The author makes a few diagnostic comments regarding the so-called constitutional bone diseases, quoting the international nomenclature and a classification which is thought to be useful for diagnosis, based on clinical and radiological criteria rather than purely structural and metabolic findings. PMID- 1870538 TI - [Blocking antibodies during specific hyposensitization immunotherapy in respiratory allergies in children]. AB - A group of 35 children affected by bronchial asthma, rhinitis and/or allergic conjunctivitis was examined; the children selected for the study had never undergone ITS before; all patients had received preventive drug and nondrug therapy for several months but none had succeeded in significantly reducing allergic clinical symptoms. Subcutaneous ITS Lofarma was prescribed for all patients (for various allergens) and blocking antibodies (IgG1 + IgG4) were assayed using a RAST system (Kit-Pharmacia) before the start of the study, and after 3, 9 and 12 months of therapy; 25 nonatopic children represented the control group. Although a certain number of allergen-specific blocking antibodies were present in all patients before the start of ITS, a significant increase in IgG1 + IgG4 specific allergens was observed after 9 months (especially for pollenosis). Compatible results were also obtained for blocking antibodies for children affected by dermatophagoides following 12 months of ITS. The aim of the present study was to evaluate the extent of the appearance of blocking antibodies in the circulation following ITS and to discover whether or not there was a correlation between their increased titre and improvement of the disease assessed by the use of clinical scores. PMID- 1870540 TI - [Non-Hodgkin's lymphoma with hepatosplenic involvement. The importance of imaging diagnosis using magnetic resonance tomography]. AB - This study evaluates the importance of magnetic resonance imaging (MR) in the exploration of the abdomen in a case of non-Hodgkin lymphoma diagnosed in a 14 year-old boy. Results are compared with those obtained using two widely used diagnostic methods: CT and ultrasonography (US). US revealed a prevalent involvement of the spleen, whereas CT showed a marked hepatic infiltration. The role of MR seems important because it allowed the contemporary and careful evaluation of hepatolienal involvement. The main advantages and drawbacks of using MR in pediatrics, and in particular in the study of the metastatic involvement of hypochondriac organs are discussed. PMID- 1870541 TI - [Hypertrophic pyloric stenosis. A unique familial case]. AB - The paper reports the case of family in which the mother and sons were affected by hypertrophic pyloric stenosis. Epidemiological, etiopathogenetic and diagnostic aspects of the disease are taken into account. PMID- 1870542 TI - [Transient alkaline hyperphosphatasemia in childhood. A report of 4 clinical cases and etiopathogenetic hypotheses]. AB - The paper reports four cases of idiopathic transient alkaline hyperphosphatasemia during episodes of acute infection of presumable viral etiology. It is interesting to note that one patient present a exanthematous febrile reaction to an anti-measles vaccination, which seems to confirm that the measles virus may be one of the possible causal factors of the pathology. The assay of alkaline phosphatase isoenzymes showed an increase in the three hepatic, bone and intestinal fractions, thus excluding a sectorial pathology (bone or hepatic). This will avoid the need to subject the child to superfluous diagnostic tests in this transient and benign condition of increased enzyme levels. PMID- 1870544 TI - [A bacteriological study of supragingival bacterial plaque in subjects undergoing orthodontic therapy]. AB - Direct contact between tooth enamel and bacteria is currently considered a sine qua non of tooth decay. Any condition which encourages the deposit and accumulation of bacterial plaque represents a risk factor for tooth decay. Dental therapy often entails the use of bands or brackets which house metal apparatus used to apply force or support mobile devices (plates, etc.). It is therefore possible to hypothesise that, by preventing its mechanical removal, dental treatment can lead to quantitative and qualitative changes in bacterial plaque. PMID- 1870543 TI - [Trisomy 18 or Edwards' syndrome. A report of 4 clinical cases]. AB - The paper describes four cases of trisomy 18 or Edwards' syndrome observed in the Pediatric Division of SS. Annunziata Hospital, Savigliano (CN) between 1/1/79 and 31/12/88. Following an illustrated description of the cases (3 males and 1 female), the epidemiological and clinical aspects of the syndrome are briefly discussed. PMID- 1870545 TI - [Dentinal lesions caused by the use of endodontic posts]. AB - An endodontic treatment has been effected on 36 extracted teeth, using drills; certain endodontic posts presently on the market have been successively inserted inside 18 teeth: Flexipost (Essential Dental System); Parapost Plus (Whaledent); dentatus (Dentatus). The teeth have been sectionized and watched through a photomicroscope to check an eventual presence of dentinal damages. PMID- 1870546 TI - [The cytotoxicity of nickel for chick embryo cells cultured in vitro]. PMID- 1870547 TI - [The CT aspects of a case of chondromatosis of the temporomandibular joint]. AB - The CT picture of a case of synovial chondromatosis of the temporomandibular joint is described. The distinctive feature of the case was the presence of ossified loose bodies surrounding the head of the condyle. Three-dimensional image reconstruction was also employed to obtain better overall visualization of the alterations. PMID- 1870548 TI - [Juvenile osteomyelitis and osteopetrosis. A case report]. AB - A case of mandibular osteomyelitis in a child affected by osteopetrosis is presented. Systemic antibiotic therapy was ineffective and surgery was required to obtain a partial control of infection. PMID- 1870549 TI - [The therapy of odontogenic abscesses. Pharmacological experimentation with lincomycin or amoxicillin]. AB - A clinical and microbiological study was carried out to assess the therapeutic efficacy of two different antibiotics, lincomycin and amoxicillin, in the treatment of patients suffering from odontogenic abscesses. Microbiological analyses revealed that the majority of infections were supported by mixed aerobic and anaerobic bacterial flora. The assessment of clinical parameters clearly showed that patients receiving pharmacological treatment with lincomycin achieved a more rapid and efficacious recovery from disease in comparison to patients treated with amoxicillin. PMID- 1870550 TI - [Sutures and suture technics. Current trends and our method in oral surgery]. AB - Suture techniques are a fundamental aspect of surgical practice in terms of the successful outcome of the operation. Even in dentistry it is important to have a clear idea of the method and the type of thread used. This paper lists the types of suture threads most commonly available today, the main techniques used and, on the basis of the authors' personal experience, explains a method used for oral surgery. PMID- 1870551 TI - [A method of acid attack for the microscopic observation of noble alloys]. PMID- 1870552 TI - [The interference of miocamycin on the adhesiveness and coaggregation of the bacteria responsible for periodontopathies]. AB - The authors studied the effect miocamycin has on the adherence and coaggregation of pathogenic bacteria in periodontopathy. The data obtained by optic microscopy, after treatment of the strains with doses of miocamycin equal to 1/4 and 1/8 of the MIC after 3 and 6 hours, shows the interference effect on the coaggregation and adhesivity of the antibiotic. These results have been confirmed by the observations obtained by scanning electron microscope (SEM). PMID- 1870553 TI - [Ceftizoxime in oral surgery]. AB - Clinical and statistical investigation on the use of ceftizoxime in the treatment of peri- and postoperative infections in odontostomatological and maxillofacial surgery. A sample of 48 patients in the Odontostomatologic Division of the Hospital of Asti is examined. Principles and experience of surgical antimicrobial prophylaxis according to its antibacterial activity, pharmacokinetic properties and therapeutic use are reported. PMID- 1870554 TI - [Polyglactin 910 (Vicryl rapid) in oral surgery]. PMID- 1870555 TI - [Caries susceptibility and caries resistance in a sample of 8140 military conscripts. The clinico-epidemiological considerations]. AB - An epidemiological study on the prevalence of dental caries and resistance in a group of 8,140 called-up soldiers. Possible etiopathogenetic factors or factors which might determine the gradual deterioration of oral health were also analysed. PMID- 1870556 TI - [The dentist, the health worker, the non-physician: an unacceptable discrimination]. PMID- 1870557 TI - [The comparative evaluation of the efficacy of surgical and nonsurgical periodontal therapy in relation to the oral hygiene conditions and the severity of the lesions]. AB - A retrospective longitudinal study was carried out to evaluate the efficacy of surgical and nonsurgical periodontal therapy in reducing pocket depth values. This evaluation was made in relation to the strictness with which patients observed professional and domestic oral hygiene and in relation to pretreatment pocket depth values. Results showed that the two forms of periodontal therapy offer comparable results in terms of pockets reduction of either restricted or considerable depth, whereas the most important element in order to achieve therapeutic success was the observation of an effective professional and domestic plaque control. PMID- 1870558 TI - Reconstruction of severe atrophy and resorption of maxillae and mandible with collagen hydroxyapatite. PMID- 1870559 TI - Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons--Florida and New York, 1988-1991. AB - During 1990 and 1991, outbreaks of multidrug-resistant tuberculosis (MDR-TB) in four hospitals (one in Miami and three in New York City) were investigated by CDC in collaboration with the reporting hospitals and state and local health departments. This report summarizes preliminary findings of the investigations and recommendations for prevention and control of MDR-TB outbreaks. PMID- 1870560 TI - Opportunistic non-Hodgkin's lymphomas among severely immunocompromised HIV infected patients surviving for prolonged periods on antiretroviral therapy- United States. AB - Since 1982, high-grade B-cell non-Hodgkin's lymphomas (NHLs) have been reported among persons with human immunodeficiency virus (HIV) infection (1); in 1985, CDC revised the surveillance case definition for acquired immunodeficiency syndrome (AIDS) to include certain high-grade NHLs. Recent surveillance findings indicate that NHLs occur among approximately 3% of all adults with AIDS reported to CDC. This report characterizes the occurrence of NHLs in a cohort of persons with AIDS or severe HIV infection who have received long-term zidovudine (AZT)-based therapy. PMID- 1870561 TI - Child passenger restraint use and motor-vehicle--related fatalities among children--United States, 1982-1990. AB - Although in recent years the increase in child safety seat use in the United States has saved lives of and prevented injuries to infants (children aged less than or equal to 1 year) and toddlers (children aged 1-4 years), the leading cause of death among U.S. children aged 1-4 years continues to be injuries to motor-vehicle occupants (1). These injuries account for the largest number of years of potential life lost before age 65 and the highest costs associated with pediatric injury (2). This report, based on data from the Fatal Accident Reporting System (FARS) (maintained by the National Highway Traffic Safety Administration), summarizes overall trends from 1982 through 1990 for motor vehicle-related fatalities among children and lives saved by child passenger restraint use. PMID- 1870562 TI - Maternal mortality surveillance, United States, 1979-1986. AB - To understand further the epidemiology and causes of maternal death, the Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC, reviewed all identified maternal deaths in the United States, including Puerto Rico, for the period from 1979 through 1986. The maternal mortality ratio for the period was 9.1 deaths/100,000 live births. The ratios increased with age and were higher among women of black and other minority races than among white women for all age groups, particularly for women ages greater than or equal to 40 years. Unmarried women had a higher risk of death than married women. Women who had received any prenatal care had a lower risk of dying than women who had received no care (RR = 0.19, 95% confidence limits (CL) 0.15, 0.23). Women who received no prenatal care had a gestational age-adjusted risk of maternal death 5.7 times that of women receiving care defined as "adequate." The risk of maternal death increased with decreasing levels of education for all age groups, particularly among women ages greater than or equal to 35 years. The causes of death varied for different outcomes of pregnancy; pulmonary embolism was the leading cause of death following the delivery of a live birth. Future studies aimed at developing strategies to reduce the risk of maternal deaths in the United States should use enhanced surveillance and collect more information about each death, which would allow for better understanding of factors associated with maternal mortality. PMID- 1870563 TI - Abortion surveillance, United States, 1988. AB - Since 1980, the number of legal abortions reported to CDC has remained fairly stable, varying each year by less than 3%. In 1988, 1,371,285 abortions were reported--a 1.3% increase from 1987. The abortion ratio for 1988 was 352 legally induced abortions/1,000 live births, and the abortion rate was 24/1,000 women ages 15-44 years. The abortion ratio was higher for black women and women of other minority races and for women less than 15 years of age. However, the abortion ratio for women less than 15 years was lower in 1988 than in any previous year since 1972. Women undergoing legally induced abortions tended 1) to be young, white, and unmarried, 2) to live in a metropolitan area, 3) to have had no previous live births, and 4) to be having the procedure for the first time. Approximately half of all abortions were performed before the eighth week of gestation, and greater than 85% were performed during the first trimester of pregnancy (less than 13 weeks of gestation). Black women and women of other minority races tended to obtain abortions later in pregnancy than did white women; however, age was a more dominant influence than race. Younger women tended to obtain abortions later than older women. Educational level strongly influenced when an abortion was performed; better educated women had an abortion earlier in gestation. PMID- 1870564 TI - Surveillance of postneonatal mortality, United States, 1980-1987. AB - In the United States, one-third of all infant deaths (deaths of infants ages 0 364 days) occurs in the postneonatal period (28-364 days). A substantial proportion of these deaths potentially could be prevented. To examine recent trends in postneonatal mortality (PNM) in the United States, the investigators analyzed birth and death certificate data for resident infants for the period from 1980 through 1987. Rates of PNM declined 11% from 3.5 to 3.1/1,000 live births among white infants and declined 16% from 7.3 to 6.1/1,000 live births among black infants. Most of the decline resulted from reduced mortality from infectious diseases and injuries. A decreased mortality attributable to sudden infant death syndrome (SIDS) among black infants additionally accounted for the decline. Autopsy rates for SIDS increased from 82% to 92% but did not differ for black infants and white infants. Birth defects-related PNM declined more among white infants than among black infants. The racial gap in PNM (rate ratio (RR) = approximately 2.0) persisted. However, the largest black/white gap occurred in the Northeast (RR = 2.5), the region with the lowest PNM. Black infants were 2.7 and 2.3 times more likely to die of infections and injuries, respectively, than were white infants. Although PNM rates declined during the 1980s, a greater rate of reduction is needed to achieve the Year 2000 objectives, especially among black infants. Such reductions are possible through improved access to comprehensive pediatric care as well as education and community-oriented prevention programs designed to reduce deaths due to infections and injuries. A better understanding of the etiology of SIDS and birth defects is critical for preventing postneonatal deaths. PMID- 1870565 TI - [The effect of menatetrenone on peritoneal adhesion]. AB - The correlation between the dose of menatetrenone and the incidence of post laparotomy peritoneal adhesion in Ryan's model was investigated with the use of rats. In the menatetrenone treated group, the menatetrenone was intramuscularly given in a dosage of 10 mg immediately after closure of the abdominal wound and every 24 hours for two days. In this group, the incidence of ceco-colonic adhesion was 54% (20/37), whereas the incidence in non-treated group was 26% (10/39) (p less than 0.012). Especially in cases with an air-drying time of 1-2 minutes, the difference between incidences of ceco-colonic adhesion in the menatetrenone and that of the non-treated group was high. The former incidence was 61% (17/28) and that of the latter was 21% (6/29) (p less than 0.01). In addition, the incidence of peritoneal adhesion was proportionally dose-dependent to the menatetrenone. In our clinical retrospective study, the incidence of post gastrectomy adhesive ileus increased with menatetrenone treatment to a significant degree. It is concluded that prophylactic administration of a large dose of menatetrenone should be avoided, because the incidence of post-laparotomy peritoneal adhesion could be increased. PMID- 1870566 TI - [Clinical and fundamental study of a squamous cell carcinoma related antigen (SCC RA) for esophageal squamous cell carcinoma]. AB - SCC-RA is one of the fractions of TA-4, extracted and purified from uterine cervical squamous cell carcinoma. I studied SCC-RA in order to evaluate its significance as a tumor marker for esophageal carcinoma. In 32 of 75 (42.7%) esophageal cancer patients, serum SCC-RA was positive. As compared with IAP and CEA, SCC-RA was the best marker to monitor esophageal cancer. SCC-RA positive patients tended to die earlier than negative ones, and it was considered to be one of the prognostic factors. In the immunohistochemical study using anti SCC-RA monoclonal antibody, both the normal epithelium and the carcinoma tissue reacted with SCC-RA. In the carcinoma tissue. SCC-RA reactivity was observed in 27 of 31 specimens (87%). However there was no correlation among the reactivity, the serum level and clinical stage. Furthermore, I studied the relationship between the tumor growth and the serum SCC-RA levels in the nude mice bearing human esophageal squamous cell carcinoma xenografts. The SCC-RA levels in mice sera gradually increased and they correlated well to the tumor volume. In conclusion, SCC-RA reflected the tumor volume and clinical stage, and SCC-RA is useful for monitoring esophageal cancer patients. PMID- 1870567 TI - [DNA ploidy in submucosal cancer of the stomach and its relationship to lymph node metastasis]. AB - The relationship between DNA ploidy and lymph node metastasis was determined in 40 cases of gastric cancer confined to the submucosa (with lymph node metastasis 20 cases and without 20 cases). The DNA ploidy patterns were classified as follows: Type D, Type A1 and Type A2. Of the 20 cases with lymph node metastasis, 1 was Type D, 7 were Type A1 and 12 were Type A2. The likelihood of lymph node metastasis was 12.5% (1/8) for Type D, 43.8% (7/16) for Type A1 and 75.0% (12/16) for Type A2. It is concluded that although gastric cancer confined to the submucosa is classified as early one, analysis of DNA content places such tumors with lymph node metastasis into the advanced cancer category. PMID- 1870568 TI - [Long-term follow-up study after pylorus-preserving gastrectomy for gastric ulcer]. AB - The long-term follow-up study of pylorus-preserving gastrectomy (PPG) for benign gastric ulcer was described in terms of postoperative subjective symptoms related to gastrectomy and recurrent ulceration. Of 134 patients who underwent PPG, 5 patients died within one month after operation, 33 patients died in the follow-up period and 22 patients have not been traced. Seventy-four patients were available for a 3-24 year follow-up (mean 16.6 years) Recurrent ulcer developed in 4 patients, 1, 2, 9 and 11 years after surgery at the greater curvature of pre pyloric region in all cases. Two patients underwent reoperation. These patients revealed higher gastric acid secretion as compared with that of one month after primary operation. But gastrin hypersecretion and G-cell hyperplasia were not recognized in these patients. According to detailed questionnaires, no patient showed the symptoms of dumping syndrome. The results indicate that PPG is preferable for the surgical treatment of gastric ulcer. PMID- 1870569 TI - [Clinicopathological studies on perineural invasion of rectal cancer with special reference to the prognosis and nerve preserving operation]. AB - Prospective studies on rectal cancer have been continued since 1982 in our department and in the present study, the significance of perineural invasion was investigated clinicopathologically in 432 cases of rectal cancer. (1) Perineural invasion in rectal cancer appeared to be closely related to the degree of progress of the cancer (depth of penetration, lymph node metastasis, liver metastasis and peritoneal dissemination), the degree of malignancy of the cancer (histologic type, lymphatic invasion and venous invasion) and the degree of inflammatory cell infiltration. (2) It was proven to be an important prognostic factor which influences recurrences and the survival rate. (3) If cases indicated for nerve preserving operation are considered to be those with no perineural invasion or with a low frequency of such invasion, it was assumed that such cases are those with well differentiated adenocarcinoma, a penetration depth of ss (a1) or less and no lymph node metastasis. PMID- 1870570 TI - [A study on the effects of preoperative radiotherapy for lymph node metastases in rectal cancer]. AB - Twenty-nine patients with rectal carcinoma who were treated by surgery only and 27 patients who received adjuvant preoperative radiation (42.6 Gy) were subjects of the present study. The entire pelvis was radiated with the dose of 30.6 Gy, and the rest 12 Gy was delivered to the primary tumor. By injecting micro activated carbon into the submucosa of the rectum near the tumor, the number of the defection of removed lymph nodes in non-radiation as well as radiation group was markedly improved, 48.6 and 54.2 respectively. The rates of distal lymph nodes metastases in irradiated patients were 25.9% (n0 74.1%, n1 14.8%, n2 11.1%, n3 0%), whereas it was 51.7% in patients who had surgical resection only (n0 48.3%, n1 20.7%, n2 17.2%, n3 13.8%). The number of metastatic lymph nodes were fewer in irradiated patients. Histopathological study indicated that preoperative irradiation was effective on decreasing the quantity of metastatic lymph nodes. PMID- 1870571 TI - [Hematolymphoid system in the liver--restoring mechanism of hemopoiesis in the regenerating liver]. AB - For the study of immunological phenomena peculiar to liver transplantation, it would be important to know well hematolymphoid system in the liver. In this paper, we report the restoring mechanism of hemopoiesis in the murine regenerating liver. 1) We found hemopoietic stem cells (HSC) and wheat germ agglutinin positive cells (WAG-PC) in both fractions of peripheral blood lymphocytes (PBL) and intrahepatic lymphocytes (IHL) from untreated C3H/He mice. The numbers of HSC and WGA-PC in each fraction gradually increased after partial hepatectomy. This change was remarkable in the population of IHL, associated more strongly with the liver. Colonies, which were generated from IHL in a fibrin clot culture system, are mainly composed of granulocytes, macrophages and mast cells. 2) We found colony-stimulating activity not only in the culture supernatant of normal nonparenchymal liver cells but in that of normal parenchymal liver cells. Furthermore, we clarified that one of colony-stimulating factors in both culture supernatants is GM-CSF. This result suggests parenchymal liver cells also release cytokines such as GM-CSF. These facts show that hematolymphoid system in the liver is a complicated network, composed of parenchymal liver cells, nonparenchymal liver cells, hemopoietic stem cells, and other cell populations. PMID- 1870572 TI - [Post-traumatic jaundice--its mechanism from a view point of hepatic mitochondrial function]. AB - It has been proposed that post-traumatic jaundice was the result of increased hemolysis, absorption of hematoma, effects of drugs, and so on. We considered that hepatic impairment in the bilirubin metabolism as a result of hepatic hypoperfusion might also be an important factor of the jaundice. Patients who developed jaundice after trauma were divided into two groups according to the maximum total bilirubin level; groups H (greater than 8 mg/dl) and L (less than 5 mg/dl). Severity of shock, levels of serum hepatic enzyme, and blood ketone body ratio were compared between the groups. Minimum systolic pressure, H 58, L 82 mmHg (p = 0.003); duration of shock (less than 80 mmHg), H 225, L 20 min (p less than 0.001); blood transfusion, H 9188, L 2914 ml (p less than 0.001); direct/total bilirubin, H 0.66, L 0.43 (p less than 0.001). Although no significant difference was noted in serum hepatic enzyme levels, blood ketone body ratios were significantly lower in group H throughout the first week. From these facts, it is considered that an impairment in the most energy requiring process of bilirubin metabolism, excretion of conjugated bilirubin from cytosol to capillary bile duct, due to post-traumatic hepatic mitochondrial dysfunction, followed by the reabsorption of conjugated bilirubin into the blood stream, would be one of factors of post-traumatic jaundice. PMID- 1870574 TI - [Detection of point mutation of Kirsten ras oncogene in pancreatic carcinoma by polymerase chain reaction]. AB - Regarding to the pancreatic cancer, outcomes of the patients surgically treated have been poor. By using polymerase chain reaction (PCR), paraffin-embedded specimens of the pancreatic carcinoma were confined point mutation in Kirsten (K) ras codon 12. Then, incidence and type of point mutation of this oncogene and correlative studies with stage, T or N factor of pancreatic cancer were analysed. Extremely high incidence of K-ras gene mutation was shown in present report. The highest mode of point mutation of K-ras oncogene was GGT to GAT coded aspartic acid. Cases without point mutation in K-ras codon 12 were significantly frequent in papillary adenocarcinoma than in tubular type. There were not correlative result among mutation types, stage and T factor of pancreatic cancer. Most patients with pancreatic cancer who survived more than 2 years have not shown mutation to aspartic acid. Four cases including two cases of mucin producing pancreatic cancer did not have point mutation in K-ras codon 12. Pathogenesis of mucin producing cancer can be distinguished from typical pancreatic cancer by detection of point mutation in K-ras codon 12 using PCR. PMID- 1870573 TI - [Management of cholangitis complicated in biliary carcinoma with hilar bile duct stenosis]. AB - We reviewed 60 cases of biliary carcinoma with hilar bile duct stenosis which had received percutaneous transhepatic cholangio-drainage (PTCD). Of the 60 cases, nine were complicated with acute cholangitis (AC) and three with segmental acute obstructive suppurative cholangitis (S-AOSC). The incidence of cholangitis was 20%. Six patients with AC and three with S-AOSC underwent hepatic resection for carcinoma. As to preoperative management for cholangitis in these 9 cases, conservative chemotherapy was effective in only 2 cases, and additional PTCD or segmental introduction of the drainage catheter under PTCS were useful in 5 cases. The remaining 2 cases with S-AOSC needed urgent hepatic resection including suppurative hepatic segments after various interventional treatments. No significant difference was found in resectability, morbidity and mortality between the cholangitis group and non-cholangitis group. In conclusion, it is emphasized that postoperative outcome of biliary carcinoma with cholangitis will be improved by adequate PTCD and/or urgent hepatic resection. PMID- 1870575 TI - [Nuclear DNA content in breast cancer in relation to postoperative recurrence]. AB - Nuclear DNA content in breast cancer patients who underwent extended radical mastectomy was investigated to evaluate its possible relation to postoperative recurrence. The most frequent site of the first recurrence in diploid type (D type) cases was the bone and the frequency was significantly higher than that in non-diploid type (N type) cases. On the other hand, the ploidy pattern in all cases associated with local or local lymph node recurrence was N type and the lung was the next frequent site of recurrence in N type case. The frequency of over 4c cells was the highest in the cases of local or local lymph node recurrence being significantly higher than in all cases of distant recurrence or of the bone recurrence. The cumulative disease-free survival rate in patients with D type breast cancer was significantly higher than that in patients with N type. These results suggest that nuclear DNA content provides important information for deciding therapy and the schedule of postoperative follow-up study based on the mode of recurrence. PMID- 1870576 TI - [Successful rewarming technique of isolated rat hearts following a long term preservation--calcium increase in a step-wise fashion]. AB - This study was designed to evaluate the successful rewarming technique of isolated rat hearts which was preserved for 24 hour. Isolated rat hearts preserved with hydroxy ethyl starch (3g/dl) solution at 15 degrees C, was rewarmed and calcium concentration of the perfusate was increased in a step-wise fashion from 0.25 to 2.5mM every 5 minutes. Other hearts were also rewarmed and perfused with normal calcium (2.5mM) solution, throughout the rewarming period. The hearts perfused with normal calcium solution contracted a few times, and then severely contractured. The heart lost its color and acquired a pale and mottled appearance. On the other hand, the hearts perfused low calcium solution started beating spontaneously, and their heart rate and left ventricular pressure was increased gradually according to the calcium increase. In addition, re introduction of normal calcium concentration did not change the cardiac parameters. This results indicated that step-wise increase of calcium concentration of the perfusate prevented heart contracture after rewarming and was a useful rewarming technique. PMID- 1870577 TI - [Hirschsprung's disease associated with intestinal malrotation in an adult and a review of literature]. AB - A 19-year-old woman was admitted to our clinic because of abdominal distention and severe constipation from infancy. Barium enema revealed a grossly dilated descending colon in the right of the abdomen. At laparotomy, with diagnosis of Hirschsprung's disease associated with non-obstructing intestinal malrotation (non-rotation type), division of the adhesion between caecum and duodenum, and modified Duhamel's procedure were performed. The association of Hirschsprung's disease and intestinal malrotation is rare, and to date only 20 infantile case have been reported. The present case would be the first adult case. PMID- 1870578 TI - [Airway obstructive disorders in experimental lung transplantation in rats: preliminary report]. PMID- 1870579 TI - [Development of 111In labeled activated carbon microspheres for analysis of mammary lymph flow by double isotope method: preliminary report]. PMID- 1870580 TI - [Enhancement of radiolabeled monoclonal antibody uptake with angiotensin II and tumor necrosis factor (TNF): preliminary report]. PMID- 1870581 TI - [Successful liver metastasis model with neuraminidase treated colon 26 adenocarcinoma via portal vein: preliminary report]. PMID- 1870582 TI - The digoxigenin:anti-digoxigenin (DIG) technology--a survey on the concept and realization of a novel bioanalytical indicator system. AB - A review is given on the novel non-radioactive digoxigenin:anti-digoxigenin (DIG) bioanalytical indicator system. After a general introduction on direct and indirect indicator systems based on previous non-radioactive indicator reactions as well as in vitro and in vivo amplification procedures the principle of the new digoxigenin:anti-digoxigenin technology is demonstrated. The novel system is based on the specific high-affinity interaction between the cardenolide digoxigenin from Digitalis plants and a digoxigenin-specific antibody coupled with a reporter group. A variety of methods for digoxigenin modification of nucleic acids, proteins and glycans are presented. In addition, various applications of the novel non-radioactive indicator system in a variety of direct or indirect detection approaches with either insoluble or soluble substrates are described. It is also shown that with these applications alternative reaction formats are used which are partly characterized by additional amplification steps. PMID- 1870583 TI - Proto-oncogene expression in cultured synovial fibroblasts of patients with rheumatoid arthritis. AB - Total RNA was isolated from cultured synovial fibroblasts of nine patients with rheumatoid arthritis and two controls (cruciate ligament ruptures). RNA was dot blotted and hybridized with nine different, cloned cellular or viral oncogene probes. None of the proto-oncogenes showed a significant difference of expression in cultured fibroblasts from patients with rheumatoid arthritis when compared to the expression of control fibroblasts. PMID- 1870584 TI - Detection of the human immunodeficiency virus genome with a biotinylated DNA probe generated by polymerase chain reaction. AB - A non-radiolabelled DNA probe was developed for detection of the human immunodeficiency virus type 1 (HIV-1) genome using the polymerase chain reaction (PCR) technology. Primers amplifying a 395 base pair segment of a portion of the polymerase region of the HIV-1 genome were used both to amplify sample target DNA and to generate a biotinylated DNA probe used in Southern blot hybridization. This probe performed as well as one produced by nick translation using biotinylated nucleotides or an enzyme labelled oligonucleotide probe. PMID- 1870585 TI - [Epidemiological study and orthodontics]. AB - Prevention is now playing a major role in all fields. An epidemiological survey of malocclusions has evaluated 6 years old children in one district in the Regione Veneto (Northern Italy). Some indications are provided as regards preventive and interceptive orthodontics (including treatment aimed to reducing the severity of problems) in the therapy of the most frequent malocclusions in this age group. PMID- 1870586 TI - [Operative and diagnostic set-up for dysfunctional patients]. AB - The application of the set-up for treatment planning and prognosis can be extended to the stimulation of the orthodontic teeth movements in the patients with TMJ dysfunctions, already repositioned, and with very severe dentoalveolar discrepancy in order to decide the indication for extractions and selection of the teeth to be extracted. The limits of this simulation always remain the function of the masticatory system. The sequences of the procedures on the articulator and the different steps on the upper and lower models are described. A patient with TMJ disorders and dento-alveolar discrepancy is presented with the different procedures of treatment as for the dysfunction as for the orthodontic problems. PMID- 1870587 TI - [Influence of adenoidal vegetation on rhinopharyngeal obstruction: cephalometric study]. AB - In this paper, the Authors propose a new method of cephalometric visualization of adhaenoids, in order to verify the amount of them as cause of an obstructive pathology. In this evaluation, related to a group of 100 individuals, was found an inversely proportional relation between adhaenoid's volume and angolar value of FHBoPA angle. PMID- 1870588 TI - [TMJ in subjects with juvenile rheumatoid arthritis: functional and cephalometric analysis]. AB - The Authors studied 21 patients affected by Juvenilis Rheumatoid Arthritis. The TMJ compromission was evaluated by un objective, clinical and radiographic examination. A teleradiographic with cephalometric analysis was also performed to all subjects. The results show a greater TMJ compromission in earlier arisen disease subjects. PMID- 1870589 TI - [Molar uprighting: biomechanical considerations]. AB - Various biomechanical systems for the molar uprighting have been described. The Authors analyze the force system delivered on the molar and on the anchorage unit. The biomechanical considerations are emphasized in each single case. PMID- 1870590 TI - [Distalization of molars with magnets: biomechanical considerations]. AB - Repelling magnets have recently been proposed to move maxillary molars distally. Although the technique presents some clinical indications, the biomechanics of tooth movement with magnets has not been clearly investigated. The results of the Author's experience suggest that the repelling magnets mainly generate a tipping movement of the crowns on the sagittal plane. The distal-tipping of the molars represents almost 50% of the total effect, the mesial tipping of the bicuspids cuspids-incisors constitutes the remaining 50%. Also, on the horizontal plane, the force generated by the magnets tends to rotate the crowns of the molars palatally. PMID- 1870591 TI - [Evaluation of transverse and sagittal expansion during functional therapy and conventional mechanical therapy]. AB - The Authors have analyzed the transversal and the sagittal dento-alveolar expansion in patients treated with functional therapy using the Frankel F.R. and with conventional orthodontic therapy. The expansion obtained can be superimposable so saying that with the functional therapy it's possible to have more trasversal and sagittal expansion it is not verified with this study. PMID- 1870592 TI - [Clinical protocol for orthodontic treatment of patients with different stages of periodontal disease]. AB - The Authors after a review of literature suggest a clinical approach to orthodontic treatment of patient with different degree of periodontal disease. They use this kind of clinical approach to guarantee the integrity and the stability of periodontal tissues. PMID- 1870593 TI - [Telethermography in diagnosis of craniomandibular dysfunction]. AB - The Authors have valued by means of the teletermography, the possibility of evaluating skull jaw disorders. The results obtained show how the teletermography is a valid means of screening and diagnosis. Moreover it is a very useful method for the valuation of the follow-up of the treatment. PMID- 1870594 TI - [Predispositions of the cranial base in the Delaire analysis]. AB - The architectural and structural cephalometric analysis described by Delaire gives indications on the basal and dental malocclusions. The study of the tendencies of the cranial base is extremely important but often not taken in consideration. In effect there are many factors that can predispose to alignments of the jaws to be considered correct even if C3 and CF1 are not in the norm. The Authors evaluate those factors and put them in the correct frame. PMID- 1870595 TI - [Bonding of "E"]. AB - When mixed dentition therapy is indicated, the Authors suggest the banding of second deciduous molars to avoid the risk of demineralization of first permanent molars. The method suggested is supported by few clinical cases, shown in the figures, where heavy forces are exerted against the second deciduous molar. PMID- 1870596 TI - [Developmental abnormalities in humans]. AB - Recently, tremendous advances have been made in our understanding of pre- and perinatal death and congenital anomaly, but many aspects of the field remain unknown and require the continued collaboration of workers in many clinical and basic science disciplines. Most of mankind dies before, not after birth, mostly due to chromosome abnormalities arising during pregenesis. A few trisomy 13 and 18 cases survive till birth by virtue of placental mosaicism; even trisomy 21 is an 80% prenatally lethal and a postnatally sublethal syndrome. Most aneuploid individuals surviving postnatally have sex chromosomes abnormalities (47,XXY, 47,XYY, 47,XXX). Until recently the term "monsters" was applied to many abnormalities of blastogenesis--i.e. the disruptions and malformations arising during the first 4 weeks of embyronic development (till the end of mesoderm formation). This includes not only acardia/acephaly, but also holoprosencephaly, sirenomelia, gross defects of cord, body wall and -stalk formation and conjoined twins, but also non-conjoined monozygotic twins with apparent high prenatal mortality and a high incidence of midline anomalies. One of the most important recent insights has been that associations, e.g. the VACTERAL association, and the relatively characteristic combination of anomalies seen in infants of diabetic mothers, represent disruptions of blastogenesis. The latter represent a particularly satisfying development in the field since it has been shown that control of the woman's blood sugar levels before, during and after conception helps to reduce the high incidence of defects of blastogenesis in infants of diabetic mothers. Most malformations arise during organogenesis in secondary or epimorphic fields and mostly represent anomalies of incomplete, less commonly of abnormal differentiation. An important distinction must be made between mild malformations (all-or-none defects of organogenesis) which are relatively innocuous and common in the population but never normal, and minor anomalies which are graded defects of phenogenogenesis (i.e. of the developmental processes during the fetal period (weeks 8-10 p.c.), and the most frequent anomalies in aneuploidy syndromes with resulting loss of family resemblance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1870597 TI - [Genetic counseling in prenatal diagnosis of cystic fibrosis]. AB - In this paper we discuss the possible results of post- and prenatal DNA-diagnosis in cystic fibrosis with respect to the modification of the risk of having an affected child, depending on how closely the affected patient is related to those seeking advice. For parents with an affected child post- and prenatal DNA diagnosis yields very reliable results and is an important factor in their decision process. In contrast to this, DNA-diagnosis for other relatives or individuals without an affected family member can lead to results which may intensify conflicts of decision making. This stresses the growing importance of genetic counseling before and after genetic diagnostic measures for cystic fibrosis. PMID- 1870598 TI - [Early detection of changes in peripheral blood vessels in children and adolescents with insulin-dependent diabetes mellitus using Doppler ultrasound]. AB - A clinically established method for early diagnosis of a macroangiopathy in a preclinical state has not been available so far. It was therefore checked whether vascular changes in diabetics can already be detected in childhood and adolescence by determination of pulse wave velocity using the Doppler ultrasound technique. The pulse wave velocity (PWV) was determined in 63 diabetics with a mean age (mean +/- s) of 16.2 +/- 3.3 years and a mean duration of diabetes (mean +/- s) of 8.5 +/- 4.7 years and in 45 control subjects with a mean age of 15.8 +/ 3.8 years by simultaneous recording of the pulse curves from the femoral artery and the posterior tibial artery. The diabetics had a very much higher PWV than the control group (mean +/- s: 10.9 +/- 1.6 m/s as compared to 9.9 +/- 0.8 m/s; p less than 0.001). In 21 out of 63 diabetics, the values were above the 2s range of controls. Indeed, nine of these 21 patients had values above the 3s range. In the diabetics, there was a significant correlation between PWV and the duration of diabetes and mean blood pressure. Vascular changes can already be demonstrated in childhood and adolescence by measurement of the PWV using the Doppler ultrasound method in diabetics. A longitudinal study would be necessary to establish whether this enables early diagnosis of macroangiopathy. PMID- 1870599 TI - [Rapid diagnosis of influenza virus infections from nasopharyngeal secretions]. AB - Since virus isolation consumes a lot of work and time, and virus specific antibodies are not detectable before several days after the onset of illness we developed an enzyme immunoassay (ELISA) for the detection of influenza A and influenza B virus antigen in nasopharyngeal specimens (NPS). This test permits antigen detection within four hours. This ELISA was tested with 119 NPS from children, most of these between 1-12 years old. Virus isolation in MDCK-cells served as control. A total of 67 influenza A/H3N2-, 10 influenza A/H1N1, and 2 influenza B viruses were isolated from cell cultures. 68 (88.3%) of the NPS reacted positive in influenza A virus antigen ELISA, 2 in influenza B virus antigen ELISA, and 9 reacted falsely-negative. The failure to detect antigen could not be solely due to low antigen concentration in the NPS because in 5 materials high concentrations of infectious virus were shown in cell culture. The test allows the rapid diagnosis of influenza virus infections with high efficacy also for laboratories without the facility to perform tissue culture. For accelerating the diagnosis by isolation of viruses in cell cultures, ELISA is useful as cell culture confirmation test, because influenza virus antigen is detectable before a cytopathogenic effect appears. PMID- 1870600 TI - [Trauma caused by shaking the infant--a special form of child abuse]. AB - The shaking of infants is an often underestimated cause of head-injuries in children. Without any external signs the diagnosis can be missed. The combination of subdural hematoma of typically interhemispheric site and retinal bleeding is pathognomonic of the shaked-baby syndrome. It is caused by acceleration deceleration movements of the head. We present three patients with whiplash shaken-injuries who were admitted to our hospital with impaired consciousness or in coma. With little external signs of injury more detailed investigations revealed other, older injuries suggesting previous abuse. The outcome was not favourable. Two of the children were discharged with minor or mild psychomotor retardation and one child was severely handicapped. As in the battered-child syndrome a good history, assessing child specific and familial risk-factors and the socioeconomic background are most important to confirm a diagnosis. This type of injury is usually part of the spectrum of child abuse. PMID- 1870601 TI - [Disorders of consciousness as an initial symptom of intestinal invagination]. AB - Two infants with intussusception were presented with lethargy and vomiting. Initially, the classical abdominal manifestations of the disease were missing. In order to avoid a delay of the correct treatment, intussusception should be considered in infants with altered consciousness and ultrasonography of the abdomen should be included in the diagnostic work up. PMID- 1870602 TI - [Infant mortality in former East Germany and West Germany--what is the future?]. PMID- 1870603 TI - [Lung function equipment for pediatric practice. Results of a comparative study]. AB - Pulmonary function tests can be performed in general practice since small computerized spirometers have been developed. Pediatricians also see many patients with respiratory disease but measurement of lung function in children requires special considerations. We examined 10 commercially available spirometers to assess their suitability for testing pulmonary function in children. PMID- 1870604 TI - Calcium phosphates in oral biology and medicine. PMID- 1870605 TI - A collaborative study on the genetic toxicology of 2-amino-N6-hydroxyadenine. PMID- 1870606 TI - Objectives of the collaborative study on the genetic toxicology of 2-amino-N6 hydroxyadenine: an exercise in genetic risk assessment. PMID- 1870607 TI - Base-pairing models to account for the mutagenicity and specificity of the purine analog 2-amino-N6-hydroxyadenine. AB - Potential base-pairing mechanisms of the purine analog, 2-amino-N6-hydroxyadenine (AHA), with the natural bases of DNA are presented. Base-pairing properties of this analog indicate that AHA may induce transitions and transversions of base pairs in DNA. PMID- 1870608 TI - The genetic activity of N6-hydroxyadenine and 2-amino-N6-hydroxyadenine in Escherichia coli, Salmonella typhimurium and Saccharomyces cerevisiae. AB - The genetic activity of 2-amino-N6-hydroxyadenine or 2-amino-N hydroxylaminopurine (AHA) and N6-hydroxyadenine or 6-N-hydroxylaminopurine (HAP) was studied in S. typhimurium, E. coli and Saccharomyces cerevisiae strains. AHA was a more potent mutagen for bacteria and a less potent mutagen for yeast than HAP. The mutagenic activity of analogs was not influenced by excision, mutagenic or double-strand DNA repair mutations. On the other hand, the uvrBdel mutation has a drastic effect on the mutagenicity and toxicity of both analogs in the Salmonella strains studied. HAP was a very potent mutagen in yeast with a low capability of inducing mitotic recombination contrary to common mutagens, possessed unique intergenic specificity and was able to induce mutations in diploids at rather high frequency. PMID- 1870609 TI - Analysis of 2-amino-N6-hydroxyadenine-induced mutagenesis in phage M13mp2. AB - The mechanism of mutagenesis induced by 2-amino-N6-hydroxyadenine (AHA) and its deoxyriboside (AHAdR) was studied by determining the nucleotide sequences of phage M13mp2 mutant DNA samples. Mutations in the lac promoter-lacZ alpha region of the phage were induced by addition of this agent to culture media in which the phage was growing inside the host bacteria. The spectrum of spontaneous mutation was also investigated. The induced sequence changes were mostly base transitions (80% with AHA and 90% with AHAdR). A few single-base deletions and additions were detected, but they were ascribable to spontaneous mutations. These results are consistent with the incorporation type mechanism proposed by Janion (this issue). In the Ames Salmonella assay, both AHA and AHAdR showed strong mutagenicity in strain TA100 but no activity in TA98. PMID- 1870610 TI - The genetic toxicology of 2-amino-N6-hydroxyadenine in eukaryotic organisms: significance for genetic risk assessment. AB - A collaborative study was designed to assess the mutagenicity of 2-amino-N6 hydroxylaminopurine (AHA) in a wide variety of eukaryotic assays systems in terms of potency and specificity. Earlier studies in Salmonella and Neurospora had shown that AHA was an extremely potent mutagen which appeared to cause predominantly AT to GC base-pair transitions. This discovery was viewed as an unusual opportunity to explore the general utility of different eukaryotic assay systems for genetic risk assessment. The objective was to determine whether AHA would show comparable potency and specificity in those eukaryotic organisms used to evaluate mutagenic potential of environmental chemicals for the human population. The data presented in this report show that AHA was mutagenic in all the eukaryotic assays utilized; however, the level of effect was found to be assay system-dependent. In addition, in assays where other base analogs were used as positive controls, differences in relative potency were observed from those obtained in the earlier studies with Salmonella and Neurospora. When alkylating agents were used as positive controls in the higher eukaryotic assays, AHA was found to have a mutagenic potency comparable to ethylnitrosourea (ENU), ethyl methanesulfonate (EMS) or methyl methanesulfonate (MMS) for many of the assays. With regard to mutagenic specificity, AHA appears to induce gene/point mutations in eukaryotic organisms, resulting predominantly from base-pair substitutions, predominantly AT to GC base-pair transitions; however, there was some unexplained variation in the ratio of these base-pair transitions and other transitions and transversions as a function of assay system. In addition, studies on the induction of micronuclei have shown that AHA induces chromosomal damage at high concentrations and low levels of survival. PMID- 1870611 TI - Mutagenicity of 2-amino-N6-hydroxyadenine at the tk locus in L5178Y strains differing in repair capabilities and karyotype. AB - The cytotoxicity and mutagenicity of 2-amino-N6-hydroxyadenine (AHA) were measured in strains of L5178Y differing in repair capabilities and karyotype. Strain LY-R83 is monosomic for chromosome 11 and is therefore hemizygous for the tk gene, while strains LY-R16 and LY-S1 are TK+/- heterozygotes. Both strain LY R83 and LY-R16 are sensitive to UV light and are presumed to be deficient in the excision of pyrimidine dimers as shown for the parental strain, LY-R (Hagen et al., 1988; Szumiel et al., 1988). Strain LY-S1 is sensitive to the cytotoxic effects of ionizing radiation and is presumed to be defective in the repair of radiation-induced DNA double-strand breaks, as shown for the parental strain, LY S (Evans et al., 1987a; Wlodek and Hittelman, 1987). The sensitivities of the three strains to the cytotoxic effects of AHA were similar. After a 4-hour treatment with AHA at 37 degrees C, the D37 for all three strains was approximately 35 ng/ml. The AHA-induced mutant frequency was similar for the hemizygous TK+ strain LY-R83 and the heterozygous TK +/- strain LY-R16, but was slightly higher for strain LY-S1 than for either LY-R strain at an AHA concentration of 100 ng/ml. The proportion of AHA-induced LY-S1 TK -/- mutants forming colonies with diameters less than 0.3 mm was much lower than following treatment with X radiation (24% vs. 61% for AHA and X radiation, respectively). These results indicate that the vast majority of AHA-induced TK -/- mutants harbor single gene mutations. AHA did not result in cyanide-insensitive oxygen uptake, and treatment with this compound did not induce a significant number of DNA single-strand breaks, DNA alkali labile lesions, or DNA degradation in either strain. However, two hours after AHA removal, DNA single-strand breaks and/or alkali-labile lesions, possibly due to the occurrence of DNA repair, were apparent in the DNA of both strain LY-R16 and strain LY-S1. PMID- 1870612 TI - Mutagenicity of 2-amino-N6-hydroxyadenine to TK6 human lymphoblast cells. AB - TK6 human lymphoblast cells (tk +/-; hprt+) were treated with various concentrations of 2-amino-N6-hydroxyadenine (AHA) for 24 h. AHA was quite toxic to TK6 cells in the dose range 0-0.05 micrograms/ml, but additional toxicity was not observed between 0.05 and 0.10 micrograms/ml. AHA induced mutations at 2 distinct genetic loci: the autosomal thymidine kinase (tk) and the X-linked hypoxanthine-guanine phosphoribosyl transferase (hprt). Significant levels of both tk-NG mutants (normal growth rate of 16-18 h, colonies visible after 10-11 days incubation) and tk-SG mutants (slow growth rate of greater than 24 h, colonies visible after 18 days incubation) were induced. 15 hprt- mutants were isolated and analyzed by Southern blot. 8 of these had normal restriction fragment patterns after digestion with PstI, EcoRI, and HindIII, and were defined as 'point' mutations; the remaining 7 had partial deletions of the hprt gene. 32 tk- mutants were also isolated. 3 of 22 normal growth mutants and 6 of 10 slow growth mutants had lost the active tk allele. These data suggest that both point mutations and larger-scale alterations are induced by AHA. PMID- 1870613 TI - Mutagenic properties of 2-amino-N6-hydroxyadenine in Salmonella and in Chinese hamster lung cells in culture. AB - The mutagenicity of the base analogue, 2-amino-N6-hydroxyadenine (AHA), was tested in Salmonella typhimurium TA100 and TA98 and in Chinese hamster lung (CHL) cells. AHA showed very potent mutagenicity in TA100 without S9 mix, inducing 25,000 revertants/micrograms. The mutagenicity increased about 2-fold upon addition of S9 mix containing 10 microliters S9. AHA was found to be one of the strongest mutagens for TA100. Addition of S9 mix containing 100 microliters S9 induced no significant increase of revertants with AHA at amounts up to 50 ng per plate. AHA was also mutagenic for the frameshift mutant, TA98, without S9 mix, the mutagenicity for TA98 being about 1/1000 of that for TA100. When the mutagenicity of AHA was tested in CHL cells, with diphtheria toxin resistance (DTr) as a selective marker in the absence of S9 mix with a 3-h treatment of cells, DTr mutants increased dose-dependently at concentrations of 2.5-15 micrograms/ml. When cells were incubated with AHA for 24 h, a 200-fold increase in the number of DTr mutants was observed; the mutagenicity was 500-fold higher than that of ethyl methanesulfonate. This marked increase of mutagenicity by prolonged incubation may indicate that AHA induces mutations mainly after incorporation into DNA. The addition of a small amount of S9 increased the mutagenicity obtained with a 3-h treatment 2-fold, but a larger amount of S9 decreased the mutagenicity as was found with S. typhimurium TA100. PMID- 1870614 TI - Genotoxic and mutagenic effects of the diagnostic use of thallium-201 in nuclear medicine. AB - In order to investigate possible mutagenic effects of in vivo exposure to low levels of ionizing radiation used in nuclear medicine, we have examined the hypoxanthine guanine phosphoribosyl transferase (hprt) mutant fraction (MF) and chromosome aberration (CA) frequency in 24 nuclear medicine patients before and after injection of thallium-201. The mean MF of the thallium-201-exposed cohort was 5.2 +/- 4.4 x 10(-6) before injection exposure. No significant difference in MF was observed 24 h later. In 11 patients who were studied on a third occasion, 30 days after thallium-201 exposure, there was again no significant difference in post-exposure as compared with the pre-exposure MF. The frequency of CA in peripheral blood lymphocytes was not significantly different, comparing pre- and 24 h to 1 month post-radionuclide exposure. Thus, thallium-201 exposure was not associated with significant elevations in MF or CA frequency in lymphocytes of exposed individuals. PMID- 1870615 TI - Evidence that methanol inhalation does not induce chromosome damage in mice. AB - Mice were exposed by inhalation to 800 or 4000 ppm methanol for 5 days, and cytogenetic effects were analyzed in blood erythrocytes, lung cells, and testicular germ cells. The results were uniformly negative; no increased frequencies of micronuclei in blood cells, of sister-chromatid exchanges, chromosome aberrations, or micronuclei in lung cells, or of synaptonemal complex damage in spermatocytes were found. From the standpoint of risk assessment, these experimental studies do not reveal any evidence of a cytogenetic hazard associated with inhalation of methanol. PMID- 1870616 TI - Bacterial mutagenicity of two cyclopentafused isomers of benzpyrene. AB - Two novel cyclopentafused polycyclic aromatic hydrocarbons, naphtho(1,2,3 mno)acephenanthrylene (cyclopenta benzo[e]pyrene) and naphtho(2,1,8 hij)acephenanthrylene (cyclopenta(ij)benzo[a]pyrene) were evaluated for mutagenic activity in the Ames Salmonella typhimurium plate incorporation assay. Both compounds required S9 metabolic activation, and showed optimal activity at low S9 concentrations (below 0.6 mg/plate). Both compounds induced frameshift and base pair substitution mutations, being active in strains TA98, TA100, TA1537, TA1538 and TA104, but not in strain TA1535. Cyclopenta(ij)benzo[a]pyrene was more active than cyclopentabenzo[e]pyrene, and both were more potent than their parent ring systems, benzo[a]pyrene and benzo[e]pyrene, respectively. Cyclopenta(ij)benzo[a]pyrene was more active in strain TA104 than in TA100 or TA98 (250-470, 340 and 80-100 rev/nmole) as was benzo[a]pyrene (120, 70 and 40 rev/nmole respectively); cyclopentabenzo[e]pyrene was more active in TA100 than TA104 or TA98 (70 versus 50 and 40 rev/nmole), and benzo[e]pyrene showed a similar pattern (4, 3.5 and 0.6 rev/nmole). The relative potencies of the four compounds are in accord with predictions based on perturbational molecular orbital calculations. The peak of activity at low S9 concentrations is consistent with epoxidation at the cyclopentafused ring being the major route of metabolic activation for both these cyclopentafused compounds. PMID- 1870617 TI - Genotoxic activity of potassium permanganate in acidic solutions. AB - Potassium permanganate (KMnO4) combined with sulfuric acid is a strongly oxidizing mixture which has been recommended for the destruction and the decontamination of various mutagens/carcinogens in the publication series of the International Agency for Research on Cancer. Evaluation of the genotoxicity of 4 potassium permanganate solutions was performed using a microtechnique of the Ames test with the tester strains TA97, TA98, TA100 and TA102 with and without metabolic activation. Presence of direct-acting mutagens was detected in all the samples with the tester strain TA102 without S9 mix (163-357 revertants/microliters of the solutions). Three samples containing either acetone or ethanol as an organic solvent also induced a mutagenic response on tester strain TA100 without S9 mix (167-337 revertants/microliters). In addition, DNA damage in human peripheral blood lymphocytes was also measured for one of the mixtures by a new technique: the single-cell gel assay (SCGA). A sample with no organic solvent induced DNA damage in human lymphocytes with a dose-response relationship as determined by SCGA. The major mutagenic agent generated by the permanganate solutions was found to be manganese ion (Mn2+). Both manganese sulfate (MnSO4) and manganese chloride (MnCl2) gave mutagenic dose-response relationships on tester strain TA102 without S9 mix. The mutagenic potencies were 2.8 and 2.4 revertant/nmole for MnSO4 and MnCl2 respectively. MnCl2 also induced DNA damage in human lymphocytes as determined by the SCGA. The genotoxic effects of KMnO4 in acidic conditions were probably mediated by the conversion of MnO4- to Mn2+. KMnO4 in alkaline solutions did not produce mutagenic species and may offer an alternative for the degradation of genotoxic compounds. PMID- 1870618 TI - Genotoxicity data supporting the proposed metabolic activation of ethyl carbamate (urethane) to a carcinogen: the problem now posed by methyl carbamate. PMID- 1870619 TI - Micronucleus induction in bone marrow by vinyl carbamate, a hypothetical metabolite of the carcinogen urethane (ethyl carbamate). PMID- 1870620 TI - Methyl carbamate: negative results in mouse bone-marrow micronucleus test. PMID- 1870622 TI - Chromosomal aberration analysis of workers in tannery industries. AB - A chromosomal aberration analysis was carried out on tannery workers and on matched controls. Workers were engaged in 2 different processing areas, the drum and the finishing workshop. A weak but significant increase in chromosomal aberration frequencies was shown in drum workers in comparison to controls, no difference was shown in finishers. PMID- 1870621 TI - Bacterial mutagenicity testing of 49 food ingredients gives very few positive results. AB - 49 substances permitted for use in food in the United States was tested for mutagenicity in the Ames Salmonella typhimurium assay and in Escherichia coli strain WP2. Four of these substances caused increases in revertant counts in S. typhimurium. Two of these four (papain and pepsin) were found to contain histidine, and therefore the results of the tests on these two substances could not be taken as demonstrating mutagenicity. The other two substances causing increases in revertant counts (hydrogen peroxide and potassium nitrite) were mutagenic. The results on one chemical, beta-carotene, were evaluated as inconclusive or questionable. The remaining 44 substances were nonmutagenic in the test systems used. It is concluded that, for those generally physiologically innocuous chemicals tested, there are very few 'false positives' in the bacterial test systems used. PMID- 1870623 TI - Micronucleus assay in biomonitoring of patients undergoing excretory urography with diatrizoate and ioxaglate. AB - In order to perform biological monitoring of exposure to radiation and contrast media, we evaluated the micronucleus count (MN) and the mitotic index (MI) in peripheral blood lymphocytes from patients undergoing excretory urography with diatrizoate (20 patients) and ioxaglate (20 patients). Three samples were taken for each patient: A (before exploration), B (immediately after exploration) and C (7 days later). There were no significant differences in the radiation doses received, nor in the dose of contrast agent, between both groups. The micronucleus count increased significantly in sample B in both groups, the increase being more statistically significant in the diatrizoate group (p less than 0.01) than in the ioxaglate group (p less than 0.05). One week later, the MN were still slightly high (p less than 0.05) in the diatrizoate group only. These results suggest a clastogenic effect which depends, to a great extent, on the nature of the contrast medium. PMID- 1870624 TI - Enhanced frequency of chromosome aberrations in workers occupationally exposed to diagnostic X-rays. AB - To estimate the level of radiation exposure of personnel handling diagnostic X ray machines, the yield of chromosomal aberrations was analysed in peripheral blood lymphocyte cultures. These occupationally exposed individuals showed higher frequencies of dicentrics as well as acentrics than normal controls. Absorbed radiation doses calculated by extrapolating reference in vitro dose-response curve for dicentrics ranged between 0.13 and 0.17 Gy. This implies exposure beyond the permissible limit of 0.05 Gy/year for the whole body. However, no obvious trend of increased aberrations as a function of either duration of employment or age was noticed. The increase in the aberration yields in this personnel underscores the need of adopting measures to avoid or minimise such overexposure. PMID- 1870625 TI - Induction of micronuclei and anaphase aberrations by cytochalasin B in human lymphocyte cultures. AB - The frequency of micronucleated cells in isolated 72-h human lymphocyte cultures treated with cytochalasin B (Cyt-B; 1.5-6 micrograms/ml for the last 28 h) was 9 21 times higher (mean 14.6 times) among multinucleate than binucleate cells. At 3 micrograms/ml, the concentration of Cyt-B originally recommended for the human lymphocyte micronucleus assay, the frequency of micronucleated multinucleate cells was 8.5%, while 0.7% of the binucleate cells had a micronucleus. Although no dose-dependent induction of micronuclei could be observed for either of the cell types, increase in the concentration of Cyt-B was associated with a decrease in the ratio of multinucleate to binucleate cells. Treatment with Cyt-B (1.5-12 micrograms/ml) increased the frequency of anaphase cells with aberrations, especially lagging chromatids. This finding was explained by a dose-dependent increase in multipolar (greater than or equal to 3 poles) divisions which had a high frequency of anaphase aberrations (39-53%), irrespective of the concentration of Cyt-B. Bipolar anaphases did not show a significant increase in aberrant cells, although a suggestive dependence on the concentration of Cyt-B was observed. The findings indicate that the high frequency of micronuclei in multinucleate lymphocytes produced by Cyt-B is due to mitotic errors arising when bi- (and multi-) nuclear cells divide. To avoid possible artifactually high micronucleus frequencies due to inclusion of cells that have divided greater than or equal to 2 times in the presence of Cyt-B, it is recommended that, in the human lymphocyte micronucleus assay using the cytokinesis-block method, the cell culture time is reduced to minimize the frequency of such cells and that only good preparations and regularly shaped binucleates are included in the analysis. PMID- 1870626 TI - Isolation of the mutagenic and DNA adduct-inducing components from a commercial preparation of HC blue 1 using Salmonella (TA98) bioassay-directed HPLC fractionation. AB - In the present study we report the separation of the mutagenic impurities from the nitrophenylenediamine hair dye HC Blue 1. This was accomplished by bioassay directed HPLC fractionation, using Salmonella strain TA98 and reverse phase HPLC analysis. The mutagenic fraction eluted between 80 and 90% methanol, whereas the HPLC fraction containing the parent compound HC Blue 1 eluted with 30% methanol and was non-mutagenic. 100% of the mutagenic activity applied to the column was recovered in fractions that did not possess the blue color of HC Blue 1. Also, HPLC-purified HC Blue 1 did not form DNA adducts (32P-postlabeling) in Salmonella strain TA98. On the other hand, commercial HC Blue 1 and the mutagenic fraction derived from commercial HC Blue 1 (HPLC-isolated) gave similar DNA-adduct profiles that consisted of 7 adducts. DNA adduction was examined concomitantly with mutagenicity and toxicity studies on the HC Blue 1 samples in TA98. The data indicated that, in Salmonella, both the mutagenicity and DNA adduction of commercial HC Blue 1 are due to impurities and not the parent compound. PMID- 1870627 TI - Recovery of polychromatic erythrocytes and micronuclei following cellulose column separation of mouse bone-marrow samples. PMID- 1870628 TI - Mutagenicity of urine from rats after 1-nitropyrene and 2-nitrofluorene administration using new sensitive Salmonella typhimurium strains YG1012 and YG1024. AB - 1-Nitropyrene (1-NP) and 2-nitrofluorene (2-NF), two of the most abundant nitro substituted polycyclic aromatic hydrocarbons (nitro-PAH) present in combustion products such as diesel engine exhaust, were administered intraperitoneally to rats at a dose of 5 mg per animal. Urine samples, 1-NP and 2-NF were tested in the Ames assay using the newly developed Salmonella typhimurium strains YG1012 and YG1024 (overproducing O-acetyltransferase) and their parent strains TA1538 and TA98. In urine, collected over 3 periods of 24 h after administration, most of the mutagens appeared during the first 24 h. The mutagenicity was found to be a factor 2-30 higher in the YG strains when compared to the TA strains. Addition of S9 mix and rat liver cytosol both with and without beta-glucuronidase increased the mutagenicity of urine samples from 1-NP-treated rats. Addition of beta-glucuronidase revealed that a considerable part of the mutagenic metabolites of 1-NP and 2-NF were excreted as glucuronide conjugates. The increase in mutagenicity of urine samples from 2-NF-treated rats after the addition of rat liver cytosol referred to N,O-acyl transfer as a step in activating 2-NF to strong mutagens. The high sensitivity of the YG tester strains indicated that these strains might be used to explore environments where people are exposed to nitro-PAH, such as work places with diesel emission sources. PMID- 1870629 TI - AAEM case report #3: myasthenia gravis. AB - Reported here are the electrodiagnostic findings in a patient with myasthenia gravis who had dysarthria, dysphagia, and dyspnea. The use of repetitive nerve stimulation and single fiber electromyography studies for the evaluation of patients suspected of myasthenia gravis is reviewed. PMID- 1870630 TI - Basal lamina and superfast myosin expression in regenerating cat jaw muscle. AB - We investigated the possible role of extracellular matrix in specifying the expression of superfast myosin during cat jaw muscle regeneration. Equal proportions of muscle tissue from jaw and limb were minced together after killing cellular elements from one source. We allowed the mince to regenerate in the bed of a fast limb muscle. Regenerates were analyzed immunocytochemically at 71 to 294 days after operation. Fibers in control regenerates containing live cells from both sources expressed fast, superfast or slow myosins, or a mixture of these myosins. In regenerates containing only one type of live cells, we detected only myosins appropriate to the live cells. Our results suggest that during regeneration the original extracellular matrix of jaw-closing or limb muscle is unable to specify the expression of superfast or fast myosins, respectively; they point to the cellular elements, probably the satellite cells, as determinants of muscle specificity during regeneration. PMID- 1870631 TI - Electrophysiological improvement following decompression surgery in tarsal tunnel syndrome. AB - Plantar nerve conduction studies 14 months to 3.5 years after decompression surgery in 3 cases of tarsal tunnel syndrome showed an improvement in motor conduction as well as in sensory nerve conduction. This electrophysiological improvement was associated with clinical improvement. However, minor abnormalities still existed in sensory nerve conduction in all 3 cases. PMID- 1870632 TI - The extent and time course of motoneuron involvement in amyotrophic lateral sclerosis. AB - The numbers and relative sizes of motor units have been estimated in 373 muscles of 123 patients with ALS: 74 of the muscles were examined on more than one occasion. The median duration between the onset of symptoms and the initial examination was 12 months; by this time, approximately 90% of the tested muscles showed losses of motor units. The evoked motor unit potentials continued to enlarge in most, but not all, muscles as the disease progressed. Once a muscle became affected by the disease process, the average time-course was such that the motor unit population halved in each 6-month period of the first year and diminished more slowly thereafter. A small proportion of patients was encountered in whom the disease progressed much more slowly and there were occasional large fluctuations in the motor unit estimates suggestive of reversible motoneuron dysfunction. PMID- 1870633 TI - External recording of twitch time course in cat ankle muscles. AB - In chronic experiments concerning the activity-dependent plasticity of muscle properties, a simple and noninvasive method was used for monitoring changes of twitch speed in conscious adult cats. The animals had been provided with implanted electrodes for nerve stimulation, and a hand-held force transducer was pressed against the fully extended ankle joint while single test pulses were delivered to the common peroneal nerve. In the present report, this technique for the recording of ankle twitches is subjected to critical analysis and evaluation. The measurements were highly reproducible with respect to contraction time (time to-peak) but less so for half-relaxation time and twitch amplitude; other methods should be used for the long-term monitoring of contractile force. The total force (torque) of the ankle twitch was mainly produced by tibialis anterior (about 45%), peroneus longus (PerL; 27%) and extensor digitorum longus (23%). The ankle twitch produced by PerL alone had about the same contraction time as that of all the muscles together. Among muscles that had become changed as a result of long term electrical stimulation there was, in general, a good correspondence between the contraction times from simple external recordings of ankle twitches and those separately measured for PerL under general anesthesia (force transducer then directly connected to PerL tendon). PMID- 1870634 TI - Correlation of motor units with strength and spectral characteristics in polio survivors and controls. AB - The purpose of this study was to determine whether quantitative motor unit analysis in postpolio individuals correlates with muscle strength, endurance, work capacity, or power spectral characteristics of surface EMG and to determine whether power spectrum differentiates postpolio from control subjects. This study was designed to compare these variables in 34 symptomatic postpolio, 16 asymptomatic postpolio, and 41 control subjects. Quantitative motor unit analysis of the quadriceps femoris muscle was performed using a concentric needle electrode. Isometric knee extension peak torque, endurance (time to exhaustion) at 40% of maximal torque, work capacity (tension time index), and recovery of force through 10 minutes post-exhaustion were determined. Median frequency of the surface power spectrum was determined during the above testing. Power spectrum histograms were compared at the onset and termination of endurance exercise. Motor unit action potential variables did not correlate with isometric peak torque, tension time index, endurance time, recovery of strength, or with median frequency. Surface power spectrum did not differentiate postpolio from control subjects. PMID- 1870635 TI - Infantile Pompe's disease, lipid storage, and partial carnitine deficiency. AB - A diagnosis of infantile Pompe's disease (glycogenosis type II) was made by muscle biopsy on a 6-month-old infant boy seen with hypotonia, weakness, and developmental regression. Histochemistry and electron microscopy revealed a vacuolar myopathy with massive glycoge accumulation associated with increased neutral lipid as demonstrated on Oil Red O reactions. Pleomorphic, hypertrophic mitochondria with distortion of cristae and electron-dense deposits within the matrix were identified. Acid alpha-1,4-glucosidase activity was absent but associated with increased neutral maltase activity and a variable compensatory rise in activity of other lysosomal enzymes. Biochemical studies demonstrated low free carnitine, normal acylcarnitine, increased activity of carnitine palmityl and acyl transferases, and other enzymes of beta-oxidation with the notable exception of low normal beta-hydroxyacyl-CoA dehydrogenase activity. The explanation for the lipid accumulation is uncertain but is likely related to the combination of low carnitine concentration in muscle, low beta-hydroxyacyl CoA dehydrogenase, representing a rate limiting enzyme of beta-oxidation, and nonspecific defective mitochondrial function. PMID- 1870636 TI - Dynamic F waves in neurogenic claudication. AB - Serial F waves were elicited before and after ambulation in 2 patients with neurogenic claudication. In both patients dynamic changes in F wave parameters consisting of either unelicitability or increased latencies occurred postexercise. The time course of these changes and their subsequent rapid reversibility over 15 minutes suggest ischemic-induced conduction block and slowing in proximal motor axons. These physiological changes may account for some of the dynamic neurological symptoms of this disorder. Moreover, F wave exercise testing may provide corroborative information for the diagnosis of neurogenic claudication. PMID- 1870637 TI - Assessment of locomotor function in young boys with Duchenne muscular dystrophy. AB - Thirty-three young boys (mean age 3.42 years) with Duchenne muscular dystrophy (DMD) and 21 normal control boys (mean age 3.51 years) were studied prospectively to determine whether it is possible to objectively assess locomotor function in young boys with DMD so that they can be included in treatment trials. An initial reproducibility study using a hand-held myometer demonstrated that this method was not useful. The Hammersmith Motor Ability Score demonstrated an increase in developmental abilities with age which was markedly different from normal. The locomotor quotient of the Griffiths' Scales demonstrated a deterioration of quotient scores and is a useful method of assessment that could be used in treatment trials involving young boys with DMD. Sample size planning for treatment trials is discussed. PMID- 1870638 TI - Fiber density: a fast and accurate way to estimate human muscle fiber areas. PMID- 1870639 TI - Electrical and magnetic stimulation of the accessory nerve at the base of the skull. PMID- 1870640 TI - Fetal fibronectin in cervical and vaginal secretions as a predictor of preterm delivery. AB - BACKGROUND: Preterm delivery is the leading cause of neonatal mortality in the United States, but efforts to address the problem are hampered by the inability to predict accurately which pregnancies are at risk. We postulated that damage to the fetal membranes may release fetal fibronectin into the cervix and vagina, giving rise to a biochemical marker for preterm delivery. METHODS: We measured fetal-fibronectin concentrations in cervical and vaginal secretions, amniotic fluid, and maternal plasma with a sensitive immunoassay using the monoclonal antibody FDC-6. Immunohistochemical studies were used to determine the distribution of fetal fibronectin in the placenta and amniochorionic membranes and to ascertain its cell of origin. RESULTS: Women with uncomplicated pregnancies (n = 163) who delivered at term rarely had cervicovaginal fetal fibronectin concentrations above 0.05 micrograms per milliliter between 21 and 37 weeks of gestation (11 of 267 cervical samples [4 percent] and 9 of 267 vaginal samples [3 percent]. High levels of fetal fibronectin were detected in amniotic fluid and in the cervical or vaginal secretions of 93.8 percent of the women with preterm rupture of membranes (n = 65). Cervical or vaginal fetal fibronectin was also present in 50.4 percent of the women with preterm uterine contractions and intact membranes (n = 117), and its presence identified the women who delivered before term (n = 60) with a sensitivity of 81.7 percent and a specificity of 82.5 percent. In the placenta and membranes, fetal fibronectin was found at points of contact with the uterine wall. CONCLUSIONS: The presence of cervicovaginal fetal fibronectin in the second and third trimesters of pregnancy identifies a subgroup of women who are at high risk for preterm delivery. This phenomenon may reflect the separation of the chorion from the decidual layer of the uterus, with the release of intact or degraded chorionic components of the extracellular matrix into the cervical and vaginal secretions. PMID- 1870641 TI - Long-term developmental outcome of infants with iron deficiency. AB - BACKGROUND: Iron-deficiency anemia has been associated with lowered scores on tests of mental and motor development in infancy. However, the long-term developmental outcome of infants with iron deficiency is unknown, because developmental tests in infancy do not predict later intellectual functioning. METHODS: This study is a follow-up evaluation of a group of Costa Rican children whose iron status and treatment were documented in infancy. Eighty-five percent (163) of the 191 children in the original group underwent comprehensive clinical, nutritional, and psychoeducational assessments at five years of age. The developmental test battery consisted of the Wechsler Preschool and Primary Scale of Intelligence, the Spanish version of the Woodcock-Johnson Psycho-Educational Battery, the Beery Developmental Test of Visual-Motor Integration, the Goodenough Harris Draw-a-Man Test, and the Bruininks-Oseretsky Test of Motor Proficiency. RESULTS: All the children had excellent hematologic status and growth at five years of age. However, children who had moderately severe iron-deficiency anemia as infants, with hemoglobin levels less than or equal to 100 g per liter, had lower scores on tests of mental and motor functioning at school entry than the rest of the children. Although these children also came from less socioeconomically advantaged homes, their test scores remained significantly lower than those of the other children after we controlled for a comprehensive set of background factors. For example, the mean (+/- SD) adjusted Woodcock Johnson preschool cluster score for the children who had moderate anemia in infancy (n = 30) was 448.6 +/- 9.7, as compared with 452.9 +/- 9.2 for the rest of the children (n = 133) (P less than 0.01); the adjusted visual-motor integration score was 5.9 +/- 2.1, as compared with 6.7 +/- 2.3 (P less than 0.05). CONCLUSIONS: Children who have iron-deficiency anemia in infancy are at risk for long-lasting developmental disadvantage as compared with their peers with better iron status. PMID- 1870642 TI - Donor-cell leukemia after bone marrow transplantation for severe aplastic anemia. PMID- 1870643 TI - Preventing preterm birth. PMID- 1870644 TI - Helicobacter pylori and peptic ulcer disease. PMID- 1870645 TI - Cost savings due to lower utilization? PMID- 1870646 TI - Wasted disposable medical materials. PMID- 1870647 TI - Fetal protection and employment discrimination--the Johnson Controls case. PMID- 1870648 TI - Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses' health study. AB - BACKGROUND: The effect of postmenopausal estrogen therapy on the risk of cardiovascular disease remains controversial. Our 1985 report in the Journal, based on four years of follow-up, suggested that estrogen therapy reduced the risk of coronary heart disease, but a report published simultaneously from the Framingham Study suggested that the risk was increased. In addition, studies of the effect of estrogens on stroke have yielded conflicting results. METHODS: We followed 48,470 postmenopausal women, 30 to 63 years old, who were participants in the Nurses' Health Study, and who did not have a history of cancer or cardiovascular disease at base line. During up to 10 years of follow-up (337,854 person-years), we documented 224 strokes, 405 cases of major coronary disease (nonfatal myocardial infarctions or deaths from coronary causes), and 1263 deaths from all causes. RESULTS: After adjustment for age and other risk factors, the overall relative risk of major coronary disease in women currently taking estrogen was 0.56 (95 percent confidence interval, 0.40 to 0.80); the risk was significantly reduced among women with either natural or surgical menopause. We observed no effect of the duration of estrogen use independent of age. The findings were similar in analyses limited to women who had recently visited their physicians (relative risk, 0.45; 95 percent confidence interval, 0.31 to 0.66) and in a low-risk group that excluded women reporting current cigarette smoking, diabetes, hypertension, hypercholesterolemia, or a Quetelet index above the 90th percentile (relative risk, 0.53; 95 percent confidence interval, 0.31 to 0.91). The relative risk for current and former users of estrogen as compared with those who had never used it was 0.89 (95 percent confidence interval, 0.78 to 1.00) for total mortality and 0.72 (95 percent confidence interval, 0.55 to 0.95) for mortality from cardiovascular disease. The relative risk of stroke when current users were compared with those who had never used estrogen was 0.97 (95 percent confidence interval, 0.65 to 1.45), with no marked differences according to type of stroke. CONCLUSIONS: Current estrogen use is associated with a reduction in the incidence of coronary heart disease as well as in mortality from cardiovascular disease, but it is not associated with any change in the risk of stroke. PMID- 1870649 TI - Chagas' heart disease in the United States. AB - BACKGROUND AND METHODS: Chagas' heart disease is believed to be rare in the United States, although many persons from countries where the disease is endemic reside here. We performed a retrospective case review and prospective follow-up of 25 patients with Chagas' heart disease and no obstructive coronary artery disease on angiography. RESULTS: The patients mainly presented with symptomatic atrioventricular block, congestive heart failure, anginal chest pain, sudden death averted by resuscitation, or sustained ventricular tachycardia. Of the 25 patients, 18 had been treated for coronary artery disease or idiopathic dilated cardiomyopathy for up to 108 months before the diagnosis of Chagas' disease was considered. The electrocardiograms frequently suggested coronary artery disease. Six of the seven patients who had exercise thallium-perfusion scans had abnormalities suggesting ischemia or infarction. A left ventricular aneurysm was found in 14 of the 25 patients, segmental akinesia or hypokinesia in 5, and diffuse hypokinesia in 3. Programmed ventricular stimulation performed in 13 patients induced sustained ventricular tachycardia in 9 and nonsustained ventricular tachycardia in 2. Actuarial survival (mean +/- SE) after four years for the entire group was 56 +/- 12 percent; it was 32 +/- 16 percent among those with global left ventricular dysfunction, and 78 +/- 14 percent among those without such dysfunction (P = 0.03). Only patients with left ventricular dysfunction or an aneurysm died (four-year survival, 45 +/- 14 percent, as compared with 100 percent for the remaining patients; P = 0.0002). Heart failure and left ventricular aneurysm or dysfunction were the only independent predictors of death. Nine patients required permanent pacemakers. CONCLUSIONS: In the United States, Chagas' heart disease commonly mimics coronary artery disease or idiopathic dilated cardiomyopathy. The prognosis is poor for patients with heart failure or left ventricular aneurysm or dysfunction. The disease may be underdiagnosed in the United States. PMID- 1870650 TI - Efficacy of statewide neonatal screening for cystic fibrosis by assay of trypsinogen concentrations. AB - BACKGROUND: To evaluate the feasibility and efficacy of measuring immunoreactive trypsinogen in blood to screen for cystic fibrosis, we performed this test in 279,399 newborns in Colorado from 1982 to 1987. METHODS: Immunoreactive trypsinogen was measured in dried blood spots when the infants were 1 to 4 days old; if the level was elevated (greater than or equal to 140 micrograms per liter), the measurement was repeated (mean age, 38 days); if the level was again elevated, sweat testing was performed (mean age, 49 days). For the second test, two cutoff levels (120 and 80 micrograms per liter) were evaluated. RESULTS: We found an incidence of cystic fibrosis of 1 in 3827 (0.26 per 1000), with 3.2 newborns per 1000 requiring repeat measurement. When adjusted for race and compliance with testing, the incidence among the white infants (1 in 2521) was close to the expected incidence. The false positive rate with the initial cutoff level (92.2 percent) was similar to the rate found in neonatal screening programs for other diseases. False negative results occurred because of laboratory error or changes in procedure (three infants) and trypsinogen concentrations lower than the initial cutoff level (three infants) or lower than the remeasurement cutoff level of 120 micrograms per liter (one infant). Sweat tests were negative in 168 infants with an elevated initial trypsinogen level but a level below 80 micrograms per liter on remeasurement, confirming the value of 80 micrograms per liter as an appropriate cutoff for repeat-test results. Overall, 95.2 percent of the infants with cystic fibrosis (95 percent confidence interval, 85 to 99 percent) who did not have meconium ileus could be identified with the use of a trypsinogen cutoff level of 140 micrograms per liter on initial testing and 80 micrograms per liter on repeat testing. CONCLUSIONS: Statewide screening for cystic fibrosis based on measurements of immunoreactive trypsinogen in dried blood spots is feasible and can be implemented with acceptable rates of repeat testing and false positive and false negative results. PMID- 1870651 TI - A randomized trial of treatment options for alcohol-abusing workers. AB - BACKGROUND: Employee-assistance programs sponsored by companies or labor unions identify workers who abuse alcohol and refer them for care, often to inpatient rehabilitation programs. Yet the effectiveness of inpatient treatment, as compared with a variety of less intensive alternatives, has repeatedly been called into question. In this study, anchored in the work site, we compared the effectiveness of mandatory in-hospital treatment with that of required attendance at the meetings of a self-help group and a choice of treatment options. METHODS: We randomly assigned a series of 227 workers newly identified as abusing alcohol to one of three rehabilitation regimens: compulsory inpatient treatment, compulsory attendance at Alcoholics Anonymous (AA) meetings, and a choice of options. Inpatient backup was provided if needed. The groups were compared in terms of 12 job-performance variables and 12 measures of drinking and drug use during a two-year follow-up period. RESULTS: All three groups improved, and no significant differences were found among the groups in job-related outcome variables. On seven measures of drinking and drug use, however, we found significant differences at several follow-up assessments. The hospital group fared best and that assigned to AA the least well; those allowed to choose a program had intermediate outcomes. Additional inpatient treatment was required significantly more often (P less than 0.0001) by the AA group (63 percent) and the choice group (38 percent) than by subjects assigned to initial treatment in the hospital (23 percent). The differences among the groups were especially pronounced for workers who had used cocaine within six months before study entry. The estimated costs of inpatient treatment for the AA and choice groups averaged only 10 percent less than the costs for the hospital group because of their higher rates of additional treatment. CONCLUSIONS: Even for employed problem drinkers who are not abusing drugs and who have no serious medical problems, an initial referral to AA alone or a choice of programs, although less costly than inpatient care, involves more risk than compulsory inpatient treatment and should be accompanied by close monitoring for signs of incipient relapse. PMID- 1870652 TI - Group A streptococcal infections and acute rheumatic fever. PMID- 1870653 TI - Uncertainty about postmenopausal estrogen. Time for action, not debate. PMID- 1870654 TI - What drives neonatal screening programs? PMID- 1870655 TI - Inpatient treatment of alcoholism--new life for the Minneapolis plan. PMID- 1870656 TI - Another approach to the AIDS epidemic. PMID- 1870657 TI - Responding to the AIDS epidemic. PMID- 1870658 TI - Video display terminals and spontaneous abortions. PMID- 1870659 TI - Solid tumors in children. PMID- 1870660 TI - Cardiac tamponade caused by primary pericardial mesothelioma. PMID- 1870661 TI - Ratio of low-density lipoprotein cholesterol to ubiquinone as a coronary risk factor. PMID- 1870662 TI - The influence of the U.S. tobacco industry in foreign markets. PMID- 1870663 TI - The struggle over physician-payment reform. PMID- 1870664 TI - GABAergic control of receptivity in the female rat. AB - GABAergic neurotransmission has been implicated in the control of the steroid dependent behavior, lordosis. GABA has dual effects on lordosis: it facilitates lordosis through actions in the medial hypothalamus (mHYP) and it inhibits lordosis through actions in the preoptic area (POA). In the present study, gonadally intact and ovariectomized female rats were behaviorally tested with a sexually active male. Brains were removed from sexually receptive female either 1 or 24 h after behavioral testing. There was a significant difference in endogenous GABA concentration in HYP and POA between receptive, postreceptive and ovariectomized nonreceptive females. Specifically, GABA levels in postreceptive females were higher in the HYP (20%) and lower in the POA (21%) in comparison to receptive females (p less than 0.05). There was also a significant change in binding parameters of 3H-muscimol in the HYP and POA of receptive females as compared to 24 h postreceptive and ovariectomized rats. Attempts to modulate 3H GABA release from hypothalamic tissue slices by estrogen or progesterone in ovariectomized rats yielded no effect on this parameter. PMID- 1870665 TI - The hypothalamus is not the origin of vasopressin and oxytocin in the rat pineal gland. AB - Immunoreactive levels of vasopressin (VP) and oxytocin (OT) were quantitated in the rat pineal gland in the middle of August, when nonapeptide levels have been reported to peak annually. The pineal levels of both VP and OT were found to be substantially elevated when sampled in August, compared to sampling in July and September. mRNA levels for OT and VP in hypothalamic nuclei (supraoptic, paraventricular, and suprachiasmatic nuclei) showed no such increases during August. A lesioning of the paraventricular nuclei did not suppress pineal VP and OT levels. Finally, the injection of colchicine into the third ventricle caused pineal VP and OT levels to increase substantially. Together, these results affirm the occurrence of a summertime rise in pineal VP and OT levels and suggest that such increases do not derive from sites of VP and OT cell bodies in the hypothalamus. Rather, they indicate that the source of these pineal nonapeptides may be the pineal itself. PMID- 1870666 TI - Regulation of vasopressin expression in cultured diencephalic neurons by glucocorticoids. AB - Glucocorticoids have long been recognized as playing a major role in the regulation of vasopressin synthesis. However, the factors determining cellular specificity and molecular mechanisms of glucocorticoid action on the vasopressin gene are not understood. In the present investigation, we used primary cell cultures derived from 14-day-old fetal rat diencephalon to investigate the regulation of vasopressin expression under controlled conditions. The experimental paradigm used ensured that only magnocellular, but not parvocellular neurons grew in the cultures. The following criteria were used to establish this phenotype. (1) Cultures were derived from fetal brain well before the time parvocellular neurons are generated, and neuronal precursors did not proliferate in vitro. (2) Vasopressinergic neurons measured some 18 x 25 microns, being conspicuously larger than the average neuronal population in vitro, and clearly larger than parvocellular neurons in vivo. (3) Neurons did not express corticotropin releasing factor in vitro. Selective neutralization of glucocorticoids contained in the serum-supplemented culture medium by the drug RU 38 486 resulted in an about 2-fold increase of numbers of vasopressinergic cells and about 4-fold increase in vasopressin mRNA, but did not affect numbers of oxytocinergic neurons or expression of general neuronal marker proteins. The effects of RU 38,486 were not dependent on synaptic communication between cultured cells, as the drug was still effective when cells were synaptically isolated by growth is in 14 mM Mg2+. RU was not mitogenic for vasopressinergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870667 TI - Computed tomography of the postoperative intervertebral disc and lumbar spinal canal: serial long-term investigation in 19 patients after successful operation for lumbar disc herniation. AB - The first part of this work, published in 1988, included 25 patients who had computed tomographic (CT) scans without contrast enhancement and plain x-rays of the lumbar spine before, 1 week after, and 6 to 7 weeks after a successful operation for lumbar disc herniation. The present study extends the follow-up period to 3 years in 19 of the 25 original patients. Clinical examinations, lateral plain x-rays, and CT scans without contrast enhancement of the operated disc were repeated. The results indicate a decrease or even a disappearance of the hyperdense extradural material thought to represent fibrosis. An image suggestive of persistent disc herniation was still present in 5 of 8 patients with this finding on early postoperative CT scans. Persistent intradiscal gas was seen in nearly half of the patients. Total normalization of the posterior extraspinal structures was the rule. There was no correlation between CT appearance and residual complaints of the patients. CT scans without contrast enhancement may be sufficient to guide the surgeon in postoperative patients with massive signs and symptoms of recurrent root compression in whom a second operation is indicated on clinical grounds. In all other cases, myelography followed by CT scans is considered appropriate to investigate failed back surgery syndrome. PMID- 1870668 TI - Large cysts of the pineal gland: report of two cases. AB - Two cases of large, nontumorous cysts of the pineal gland are reported, the histopathology of which was confirmed using surgically resected specimens. Both patients were middle-aged, and the pineal cysts were found incidentally. The histopathological findings in the two cases were strikingly similar to each other and were characterized by the following points: 1) the cyst wall typically consisted of three layers, namely, collagenous fibers, glia-like cells, and normal pineal cells; 2) the cyst wall was relatively thin, approximately 100 to 300 microns in thickness; and 3) deposits of calcification almost always existed on the side of the layer of collagenous fiber. Because these findings are clearly different from those previously reported, large benign cysts of the pineal gland, or at least some of them, may constitute a new pathological entity. It is important to consider this possible pathological diagnosis when dealing with pineal cysts. PMID- 1870669 TI - Deafness after bilateral midbrain contusion: a correlation of magnetic resonance imaging with auditory brain stem evoked responses. AB - A 46-year-old woman became deaf after a closed head injury. When a computed tomographic scan failed to disclose the cause, conversion disorder was suspected. Magnetic resonance imaging, however, showed bilateral contusions of the inferior colliculi, providing objective evidence for an organic cause of hearing loss. Auditory brain stem evoked responses and stapedial reflexes also provided objective evidence of brain stem injury. This case illustrates the phenomenon of dorsal midbrain injury after head trauma. It indicates the sensitivity of magnetic resonance imaging for small focal lesions after head trauma, and it demonstrates some difficulties in the diagnosis of "hysterical" deafness. PMID- 1870670 TI - Arteriovenous malformation in meningothelial meningioma: case report. AB - An unusual association of a meningioma and an arteriovenous malformation is reported. A 68-year-old man developed left homonymous hemianopsia, left hemiparesis, and gaze palsy. Magnetic resonance imaging showed a right occipital mass lesion containing multiple signal-void areas with tubular and honeycomb appearance, suggesting a marked vascular component. An angiogram showed abnormal vasculature in the mass supplied by the posterior cerebral artery and a dural arteriovenous malformation on the tentorium. Neuropathological examination after total removal of the mass revealed a meningothelial meningioma including major portions of an arteriovenous malformation that extended from the dura and leptomeninges, through the meningioma, and into the occipital lobe, where the tumor was located. PMID- 1870671 TI - Meningioma: the role of a foreign body and irradiation in tumor formation. AB - A case of meningioma is reported. At the age of 18 years, the patient had undergone insertion of a Torkildsen shunt through a posteroparietal burr hole for obstructive hydrocephalus secondary to a tumor of the pineal region, of which no biopsy had been made. After the hydrocephalus was relieved, he underwent irradiation of the tumor. Thirty years later, he was treated for an intracranial meningioma wrapped around the shunt. The tumor followed the shunt in all of its intracranial course. Microscopy disclosed pieces of the shunt tube within the meningioma. The role of a foreign body and irradiation in the induction of meningiomas is discussed, and a comprehensive review of the literature is presented. PMID- 1870672 TI - Ossifying fibroma in the sylvian fissure: case report. AB - A rare case of an ossifying fibroma that developed in the sylvian fissure is reported here. During surgery, branches of the middle cerebral artery were encased in osseous tumor. The encased branches were divided and reanastomosed after the mass was removed. Postoperative angiograms demonstrated patency of the anastomosed arteries and a postoperative magnetic resonance imaging scan revealed no infarction distal to the arterial anastomoses. The authors recommend division and anastomosis of the encased arteries rather than partial removal of tumor from around the encased arteries, resulting in residual tumor being left behind. PMID- 1870673 TI - Intracranial fibromatosis. AB - Fibromatoses are uncommon infiltrative lesions affecting musculoaponeurotic structures, most often of the limbs and trunk. Lesions involving the cranial cavity are rare and require the same aggressive surgical management as elsewhere in the body. This case illustrates their clinical and neuroradiological features and underscores the necessity for aggressive resection to avoid recurrence. The literature is reviewed. PMID- 1870674 TI - Malignant prolactinomas. AB - Six cases of malignant prolactinoma have been reported; an additional two cases are presented here and the literature is reviewed. Diagnosis rests upon evidence of metastasis rather than histological criteria per se. Cases have arisen from known adenomas, particularly the invasive type. Bromocriptine is a useful palliative. The features and treatment of malignant prolactinoma are discussed. PMID- 1870675 TI - Spontaneous spinal subdural hematoma: case report and review of the literature. AB - We report the case of a pediatric patient with a spontaneous spinal subdural hematoma that was not associated with a coagulation abnormality. Six cases have been reported previously. The patient improved after surgical drainage. The possible causes of this rare problem are discussed. PMID- 1870676 TI - Herniated L4-L5 disc after placement of Harrington instrumentation for a fracture of the thoracolumbar spine. AB - The authors report a case in which L5 radiculopathy developed acutely after surgery for placement of Harrington rod instrumentation for an L1 body fracture. Computed tomographic myelography demonstrated a large L4-L5 herniated disc that had not been present in preoperative studies. An emergency laminectomy was performed, and a large, free, subligamentous disc fragment was removed. The patient subsequently regained L5 sensorimotor function. The postoperative development of lumbar radiculopathy is an uncommon complication of Harrington rod instrumentation that may result from several biomechanical features of the instrumentation. These injuries may not be detected by intraoperative monitoring of somatosensory evoked potentials, and therefore, the postoperative neurological examination assumes a crucial role in the early diagnosis of these lesions. As our case demonstrates, these radicular deficits may be reversible if their cause is promptly recognized and treated. PMID- 1870677 TI - Spinal cord herniation associated with an intradural spinal arachnoid cyst diagnosed by magnetic resonance imaging. AB - Two rare cases of spinal cord herniation associated with intradural spinal arachnoid cyst are reported. A preoperative magnetic resonance imaging scan demonstrated the presence of spinal cord herniation, identified as a protrusion continuous with the spinal cord. Surgery upon the intradural spinal arachnoid cyst improved progressive neurological dysfunction. The authors postulate that spinal cord herniation occurred for the following reason: The pressure of the intradural arachnoid cyst on the dorsal aspect of the spinal cord caused thinning of the dura, leading to a tear and, thus, the development of an extradural arachnoid cyst. Along with the enlargement of intradural arachnoid cyst, the spinal cord herniated through the tear in the dura into the extradural arachnoid cyst. PMID- 1870678 TI - Acoustic schwannomas in children. AB - The clinical presentation and treatment of three cases of acoustic schwannoma occurring in children are described. All the tumors were detected late, when they had attained a large size and were extremely vascular. The use of preoperative tumor embolization as an adjunct to surgical excision is discussed. PMID- 1870679 TI - Transfalcine approach to a callosomarginal artery aneurysm. AB - We describe a transfalcine approach to clipping and subsequently excising an expanding mycotic callosomarginal aneurysm. The patient had a devastating dominant (left) hemispheric spontaneous intracranial hemorrhage and was neurologically improving at the time of surgery nearly 2 months later. To avoid retracting the left hemisphere, we approached this left callosomarginal aneurysm from the nondominant side through the falx. The approach was straight-forward, and the result was satisfactory. PMID- 1870680 TI - Internal carotid-internal jugular fistula. PMID- 1870681 TI - Magnetic resonance imaging in the preoperative evaluation of cervical radiculopathy. PMID- 1870682 TI - Unusual causes of trigeminal neuralgia. PMID- 1870683 TI - Neurotoxicity after intracarotid 1,3-bis(2-chloroethyl)-1-nitrosourea administration in the rat: hemodynamic changes studied by double-tracer autoradiography. AB - Changes in blood-brain (BBB) permeability and local cerebral blood flow after intracarotid administration of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were examined quantitatively in rats with double-tracer autoradiography using [14C]alpha-amino-isobutyric acid and [18F]fluoroantipyrine. Forty-eight female Wistar rats were divided into four groups. The control group (Group 1) received 1 ml of 5% dextrose. The other three groups received three different doses of BCNU dissolved in 5% dextrose: Group II rats received 1 mg, Group III 3 mg, and Group IV 10 mg. The tracer study was performed on Day 1 or Days 4 to 12 after intracarotid administration of BCNU. In 11 rats in Group II, there were no changes of BBB permeability. Transient BBB permeability changes were seen in the striatum or hippocampus in 3 of the 5 rats (60%) in Group III within 24 hours. In 8 of 9 rats (89%) in the same group, late BBB permeability changes were observed in the hypothalamus with or without histological changes. BBB permeability changes were seen in all rats of Group IV. Focal increase of local cerebral blood flow on the infused side compared with the non-infused side of the brain was observed, although not at a significant level, in 5 of 25 rats examined with [18F]fluoroantipyrine. The results of BBB permeability and histological examinations and study of heterogenous distribution by [18F]fluorodeoxyglucose indicated that the ipsilateral subcortical structures such as the hypothalamus, amygdala, internal capsule, and caudate putamen have the highest incidence of neurotoxicity, which are closely related to histopathological damage seen in human BCNU leucoencephalopathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870684 TI - Computer- and robot-assisted resection of thalamic astrocytomas in children. AB - Six children ranging in age from 2 to 10 years who harbored deep benign astrocytomas were operated upon using a computer- and robot-assisted system. A radical excision was achieved in all cases with no significant morbidity nor any mortality. The system consists of an interactive, three-dimensional display of computed tomographic image contours and digitized cerebral angiograms taken using the Brown-Roberts-Wells stereotactic frame. The surgical retractor is held and manipulated using a PUMA 200 robot. The position and orientation of the surgical retractor is displayed on the three-dimensional display. Preoperative planning and simulation are important features of this system. Movement of the brain after removal of the tumor and cerebrospinal fluid is substantial, so the tumor removal is based on visually defined margins. Enhanced computer graphics and robotic devices are important adjuncts to neurosurgical procedures and will find increasing use in the future. PMID- 1870685 TI - Extramedullary hematopoiesis in cerebellar hemangioblastoma. AB - Extramedullary hematopoiesis and paraneoplastic erythrocytosis are uncommon in cerebellar hemangioblastoma, and their concomitant occurrence has not been reported. In a study of 26 cases of hemangioblastoma, we found extramedullary hematopoiesis in 4 tumors; one was associated with erythrocytosis. The significance of this association and the possible histogenetic origin of extramedullary hematopoiesis in cerebellar hemangioblastoma are discussed. PMID- 1870686 TI - The role of radiosurgery in the management of chordoma and chondrosarcoma of the cranial base. AB - Despite conventional multimodality treatment (surgery and fractionated radiation therapy), recurrence and clinical progression of cranial base chordomas and chondrosarcomas are common. The malignant behavior of these tumors is a result of their critical location, locally aggressive nature, and high recurrence rate. To explore the role of radiosurgery in the treatment of these skull base neoplasms, we assessed its use in four patients with chordoma and two with chondrosarcoma. In five of the patients, radiosurgery was used as adjuvant therapy for residual or recurrent tumors after surgical debulking, and in one patient with a chordoma, it was the primary treatment. No patient received fractionated external beam radiotherapy. All tumors were less than 30 mm in diameter and were treated with 20 Gy to the tumor margin. Skull base computed tomography and magnetic resonance images were essential to define the anatomic relationships between tumor and adjacent basal structures. During follow-up (mean, 22 mo; range, 8-36 mo), we found no progression of the treated tumor volume in any patient. Neurological deficits before treatment improved in three patients; the other three patients remained in stable neurological condition. Serial follow-up imaging studies demonstrated that two patients showed reduction in tumor size and four patients had no tumor growth. In one patient, a metastatic parietal lobe chondrosarcoma developed and was treated by microsurgery. Another patient showed tumor progression outside of the radiosurgical treatment volume. Our results attest to the value of stereotactic radiosurgery as an adjuvant or primary treatment for selected patients with chordoma or chondrosarcoma and demonstrate its potential advantages over standard fractionated irradiation. Analysis of the long-term clinical and imaging effects after radiosurgery is warranted. PMID- 1870687 TI - Pituitary microcirculation: physiological aspects and clinical implications. A laser-Doppler flow study during transsphenoidal adenomectomy. AB - The anterior and posterior pituitary lobes (AL and PL, respectively) are assumed to differ in the type of vascular supply and structure of their microvascular networks. Animal experiments have shown that the pituitary microvascular flow differs between the two lobes, being extremely high in the PL and low in the AL. For technical reasons, it has hitherto not been possible to study pituitary microflow in humans. Laser-Doppler flowmetry (LDF) is now a well-established method for real-time monitoring of microcirculation, applicable also in humans. In a prospective clinical study, the microflow in the AL and PL was measured during transsphenoidal microsurgery in 52 patients with adenomas of different size, growth characteristics, and endocrinological activity. The mean microflow in the PL (177.7 +/- 12.6 [flux]) was found to be about six times higher than that in the AL (27.4 +/- 2.7 [flux]). No difference in the laser-Doppler fractional volume of the lobes could be detected (0.73 +/- 0.06 [] vs. 0.77 +/- 0.07 [], where [] designates the ratio of the alternating current output to the direct current output signals). Microflow within the pituitary lobes was influenced neither by the histological type nor the size of the adenoma. Additionally, LDF signal-averaging triggered by the electrocardiogram allowed detection of different characteristic pulsatile microvascular flow patterns in the AL and PL. Our findings provide strong physiological support for the idea that the angioarchitecture of the pituitary lobes differs. With this method, the AL and PL can be identified objectively during surgery. LDF might provide useful information concerning intraoperative surgical approach. PMID- 1870688 TI - Extent of mesiobasal resection determines outcome after temporal lobectomy for intractable complex partial seizures. AB - The extent of resection was assessed in 94 patients who underwent temporal lobectomy for medically intractable complex partial seizures originating from a unilateral seizure focus in the anteromesial temporal lobe. Postoperative magnetic resonance imaging in the coronal plane was used to quantify the extent of resection of lateral and mesiobasal structures according to a 20-compartment model of the temporal lobe. Successful seizure outcome (greater than or equal to 90% reduction in seizure frequency) was accomplished in 83% of the patients (all followed up for more than 1 year; mean duration of follow-up, 25.2 months) and correlated significantly (P less than 0.05) with the extent of mesiobasal resection, regardless of the extent of resection of lateral structures. Successful seizure outcome was accomplished in 81% of the patients with no structural lesions, and also correlated significantly (P less than 0.05) with the extent of mesiobasal resection regardless of the extent of lateral resection. A successful seizure outcome was accomplished in 90% of the 21 patients with structural lesions documented by neuroimaging studies. Two patients who underwent extensive lobectomy without resection of the structural lesion had no reduction in seizure frequency postoperatively. We conclude that the most important factor in determining the outcome of temporal lobectomy in patients with unilateral anteromesial temporal lobe epileptogenicity is the extent of resection of structures in the mesiobasal temporal lobe. In patients with structural lesions, lesion resection may be an added contributor to successful seizure outcome. PMID- 1870689 TI - Complete temporal lobectomy for surgical resuscitation of patients with transtentorial herniation secondary to unilateral hemispheric swelling. AB - Transtentorial herniation is an ominous finding in the patient with head injuries. We report our experience with 10 patients suffering from acute transtentorial herniation secondary to posttraumatic unilateral hemispheric swelling who were treated aggressively with temporal lobectomy. Eight patients were men and 2 were women. Their ages ranged from 22 to 61 years, with a mean of 37 years. Their preoperative Glasgow Coma Scale scores ranged from 3 to 6, with a mean of 4. All patients had both computed tomographic and clinical evidence of unilateral hemispheric shift and acute herniation without a significant subdural or epidural hematoma. Seven patients had unilateral nonreactive pupils and 3 had bilateral nonreactive pupils. All were taken to the operating room within 2 hours of clinical signs of herniation. Complete unilateral temporal lobectomies including the mesial structures, amygdala, and uncus were performed. In this series, the mortality rate was 30%, including a single patient who was neurologically stable but died from nonneurological injuries. Of the 7 survivors, 4 were functionally independent and 3 required minimal assistance with the activities of daily living. Aggressive, early decompression via complete temporal lobectomy may thus significantly improve the outcome in patients with transtentorial herniation accompanying posttraumatic hemispheric swelling and midline shift. PMID- 1870690 TI - Civilian craniocerebral gunshot wounds. AB - Experience with 120 patients who incurred a gunshot wound to the head with dural penetration is presented. All of the patients were managed by a standard resuscitation protocol and assigned a clinical grade based on their level of consciousness both at the time of presentation and at 2 to 4 months after injury. Fifty patients (42%) underwent surgery. Twenty-eight patients (23%) had a good recovery, 19 (16%) were moderately disabled, 6 (5%) were severely disabled, and 67 (56%) died. All patients who were alert and awake with a normal or near normal neurological examination at the time of admission survived with a good outcome. All but 4 patients who were comatose at the time of admission died. Nine patients, however, who were not comatose at the time of admission died from potentially preventable causes. In 3 of these patients, a more aggressive diagnostic approach (including cerebral angiography) may have altered their ultimate outcome. An expeditious approach to the trauma victim with a comprehensive management scheme after injury may have altered the course in the remainder of these patients. PMID- 1870691 TI - Clinical application of a patient-controlled apparatus for ventricular administration of morphine in intractable pain: report of 28 cases. AB - The authors developed a patient-controlled apparatus (L-224) for ventricular administration of pain-relieving medication and utilized it in the treatment of 28 patients with intractable pain. The initial dose of morphine hydrochloride was 1 mg, which afforded pain relief for an average of 170 hours. At an average dose of 1.8 mg, the average time of pain relief obtained was 137 hours. Therefore, they conclude that L-224 is a satisfactory apparatus for the ventricular administration of pain medication; it is patient controlled, safe, and reliable in clinical application. PMID- 1870692 TI - Monitoring of somatosensory evoked potentials during surgery for middle cerebral artery aneurysms. AB - Somatosensory evoked potentials (SEPs) were monitored during 53 procedures for aneurysms of the middle cerebral artery (MCA). "Significant" changes were reported to the surgeon, who took corrective action when possible. Changes in the SEPs were categorized as follows: Type I, no change; Type II, significant change with complete return to baseline; Type III, significant change with incomplete return to baseline; Type IV, complete loss with no return; and Type V, no response at baseline. Only 1 of 37 patients with a Type I SEP had a new neurological deficit, and this was a patient who could not be examined for several days after surgery because he was in a pentobarbital coma. All 4 patients with Type III and IV changes had new postoperative neurological deficits. Perhaps of greater importance, 4 of 5 patients with Type II changes had no new deficit. These patients all had changes in SEPs that were completely reversible by clip adjustment (2), prompt removal of temporary clips (1), and inducing hypertension after aneurysm trapping (1). These cases may, therefore, represent instances in which SEP monitoring allowed the clinicians to prevent a neurological deficit. The MCA supplies the area of the somatosensory cortex that controls the hand. Median nerve SEPs are, therefore, a theoretically ideal monitor during surgery for MCA aneurysms. This study suggests that the results of MCA aneurysm surgery may be accurately predicted and improved with SEP monitoring. PMID- 1870693 TI - Cervicocranial arterial dissection. AB - Dissection of the cervicocranial arteries is becoming more frequently recognized as a cause of neurological disorders. Typical clinical features seen with dissection include unilateral headache, oculosympathetic palsy, amaurosis fugax, and symptoms of focal brain ischemia. The diagnosis of carotid or intracranial dissection is usually best confirmed by angiography, although magnetic resonance imaging and computed tomography have been shown to visualize intimal dissection. The prognosis in cases of spontaneous dissection is generally benign unless the initial manifestation involves infarction with substantial deficit. The best approach to treatment appears to be the administration of the anticoagulant, heparin, followed by warfarin or antiplatelet therapy. Surgical intervention is reserved for cases of progressive or recurrent ischemic complication that occurs despite the administration of adequate doses of anticoagulants. PMID- 1870694 TI - Giant aneurysms of the horizontal segment of the anterior cerebral artery: report of two cases. AB - Two cases of giant aneurysm of the horizontal segment of the anterior cerebral artery (A1) are presented. The rare occurrence of a giant aneurysm in this location necessitates evaluation of the cross-flow through the anterior communicating artery when planning surgical strategy. On the basis of angiographic findings, trapping of the A1 on both sides of the aneurysm neck was performed in Case 1, and aneurysmorrhaphy utilizing an angioplastic multiple clipping method of A1 endarterectomy was accomplished in Case 2. The postoperative courses of both patients were satisfactory. PMID- 1870695 TI - The thalamic clock: emergent network properties. AB - Rhythmical oscillation of thalamic neuronal populations occurs under physiological conditions and in several disease states. In the present experiments we examined the network properties of population rhythmicity and the possible involvement of N-methyl-D-aspartate receptors in the frequency regulation and maintenance of rhythmic thalamic bursts. Multisite recording of neuronal activity and local microinjections of drugs were performed on the freely moving rat. Rhythmic thalamic population bursts at 6 to 9 Hz and concurrent neocortical high voltage spike-and-wave spindles were observed during awake immobility, with the thalamic rhythm leading the neocortical high voltage spindle. Even though all individual thalamocortical neurons fired in a phase locked manner to the high-voltage spindle, the majority discharged at a significantly lower frequency than that of the population (multiunit) activity. In contrast, neurons in the nucleus reticularis thalami discharged at the frequency of the population bursts. Neurons in the extrapyramidal system and neocortex but not the hippocampal formation also fired in a phase-locked manner to the high-voltage spindle. Systemic administration or local microinjection of either non-competitive or competitive N-methyl-D-aspartate blockers (ketamine or ap-5) slowed the frequency of thalamic multiunit bursts and associated high voltage spindles from 8 to 2 Hz, or completely blocked rhythmicity. Unilateral thalamic injection of ketamine or ap-5 resulted in a suppression of the amplitude of high-voltage spindles in the injected hemisphere. It is concluded that thalamic rhythmicity is not due to the "pacemaker" properties of thalamic cells but is rather an emergent property of the relay thalamus-nucleus reticularis network. Furthermore, we hypothesize that the frequency of network oscillation is regulated by the interplay between two major classes of voltage-dependent conductances in the thalamocortical cells: low-threshold calcium channels and high-threshold N-methyl-D-aspartate channels. PMID- 1870697 TI - Effect of perforant path lesion on pattern of glutamate-like immunoreactivity in rat dentate gyrus. AB - To investigate the relation between perforant path and the pattern of glutamate like immunoreactivity in its target regions in the rat hippocampal formation, unilateral lesions of various size and location were placed to interrupt certain contingents of these afferent fibers. Postembedding immunohistochemistry at the level of light microscopy yielded the same pattern of immunoreactivity in the hippocampal formation contralateral to the lesion as in untreated animals. On the ipsilateral side, however, extensive transections of the perforant path led to a drastic loss of glutamate-immunoreactive terminal-like elements in the outer part of the dentate molecular layer. More restricted lesions induced a loss of punctate glutamate-like immunoreactivity in narrower bands within this zone. The width and the location of the affected bands appeared to depend on the extent of the transections and their topographical relation to the perforant path fiber system. These results and those obtained using a postembedding immunogold method at the level of electron microscopy strongly indicate that perforant path terminals in the dentate molecular layer of the rat contain high levels of glutamate and, thus, provide further support for an already well-documented role of this excitatory amino acid as neurotransmitter in this system. PMID- 1870696 TI - Thalamocortical responses of mouse somatosensory (barrel) cortex in vitro. AB - We have developed a novel slice preparation of the mouse somatosensory forebrain. This preparation is unique in including both the ventrobasal nucleus of the thalamus and the sensorimotor "barrel" cortex in a 400-microns-thick slice with the functional connectivity between them preserved, and in allowing direct visualization of the various components of the barrel system in unstained living tissue. Thalamocortical connectivity was demonstrated by recording the laminar profile of cortical field potentials evoked electrically from the ventrobasal nucleus. Current-source density analysis of this profile showed that the largest and earliest sinks were coextensive with the two known sites of thalamocortical terminals, layer IV and the junction of layers V and VI. The sink in layer IV could be dissociated experimentally into a small, early sink of presynaptic origin (most probably a presynaptic spike volley in the thalamocortical terminals) and a later, larger sink generated postsynaptically. By mapping the subcortical stimulation sites that elicited a response at different layer IV recording sites we concluded that the thalamus-to-cortex projection preserves the general dorsoventral relationship of the afferents. Intracellularly recorded responses elicited by thalamic stimulation included (but were not limited to) monosynaptic excitatory and disynaptic inhibitory postsynaptic potentials. The thalamus-to-cortex connections were also mapped with the axonal fluorescent tracer dioctadecyl-tetramethylindocarbocyanine perchlorate. The thalamo-cortical slice is a very suitable system for studying the physiology and pharmacology of the thalamocortical synapse and for exploring the synaptic circuitry of the somatosensory cortex. PMID- 1870698 TI - A long-lasting decrease in the inhibitory effect of GABA on glutamate responses of hippocampal pyramidal neurons induced by kindling epileptogenesis. AB - Experiments were carried out to test whether changes in the sensitivity of hippocampal pyramidal neurons to the neurotransmitters glutamate, GABA and noradrenaline may be associated with the establishment of an epileptogenic focus induced by kindling. The effects of iontophoretically applied neurotransmitters on the firing rate of single units were quantified in the rat hippocampal CA1 area in kindled and control animals. Kindling was induced by electrical tetanic stimulation of the Schaffer collateral/commissural fibers. Firing was evoked by local glutamate iontophoresis while simultaneous GABA or noradrenaline application suppressed this response. A significant reduction of the GABAergic inhibitory action on the firing rate in kindled animals studied around four or around 42 days after the last convulsion was found. In the same neurons, the suppressive effect of noradrenaline was not different from controls. The neurons of kindled animals, investigated around four days after the last seizure, had a reduced sensitivity for glutamate; more glutamate ejection current was needed to evoke firing or to evoke the maximum firing rate. In contrast, the responsiveness for glutamate was significantly increased long-term after the last convulsion. These findings demonstrate that hippocampal Schaffer collateral kindling is associated with a long-lasting reduced effectiveness of the GABA-mediated response on glutamate-evoked firing in CA1. PMID- 1870699 TI - Cellular and subcellular redistribution of glutamate-, glutamine- and taurine like immunoreactivities during forebrain ischemia: a semiquantitative electron microscopic study in rat hippocampus. AB - The effect of 20 min of ischemia on the cellular and subcellular distribution of glutamate, glutamine and taurine in the rat hippocampus was studied by means of an immunocytochemical procedure based on antisera raised against protein glutaraldehyde conjugates of the respective amino acids. Forebrain ischemia was induced by temporary occlusion of the common carotid arteries in rats with permanently occluded vertebral arteries. Within 90 s after removal of the carotid ligatures, the rats were perfused through the heart with a mixture of glutaraldehyde and paraformaldehyde. For semiquantitative electron microscopic analysis, ultrathin sections were incubated in a primary antiserum followed by a secondary antibody coupled to colloidal gold particles. The gold particle densities over different tissue compartments within the CA1 field and the mossy fiber zone of the hippocampus were determined by means of a specially designed computer program, and values from normal and ischemic animals were compared. It was found that in the astrocytes, the level of immunoreactivity for glutamine and taurine is unchanged or slightly decreased after ischemia, while that for glutamate is increased, particularly within the mitochondria (by about 100%). In contrast, pyramidal cell bodies display a reduced immunolabeling for all three amino acids following the ischemic episode. The results show that ischemia causes a redistribution of glutamate from neurons to glia. The observed increase in the glial immunolabeling for glutamate indicates that the capacity of the glial cells to metabolize glutamate is exceeded during ischemia. This glial response to ischemia has not previously been recognized and may play a role in the chain of events leading to "excitotoxic" cell death during or following an ischemic episode. The reduction of glutamate and taurine immunolabeling in neurons points to a possible amino acid efflux and is compatible with previous biochemical studies demonstrating an elevated extracellular level of these amino acids during ischemia. PMID- 1870700 TI - Plasmalemmal appositions between cholinergic and non-cholinergic neurons in rat caudate-putamen nuclei. AB - We have observed that in rat caudate-putamen nuclei, neurons immunolabeled for choline acetyltransferase were sometimes in direct apposition to unlabeled perikarya and dendrites [Pickel V. M. and Chan J. (1990) J. Neurosci. Res. 25, 263-280]. Similar juxtapositions between plasmalemmas of nerve cells each receiving input from one common terminal have been associated with activation of certain central neurons [Theodosis D. T. and Poulain D. A. (1989) Brain Res. 484, 361-366]. Thus, we sought to determine the relative abundance and ultrastructure of the appositions and the frequencies of shared synapses between choline acetyltransferase-labeled and unlabeled neurons in the rat striatum. A monoclonal antibody raised against choline acetyltransferase was localized in semi-adjacent ultrathin sections through 24 neurons in the dorsolateral caudate-putamen nuclei. Five of these choline acetyltransferase-labeled perikarya showed direct somatic appositions with unlabeled neurons. The remaining 19 of the choline acetyltransferase-labeled perikarya did not show somatic appositions with unlabeled perikarya; however, when traced through multiple (20-100) semi-adjacent sections their dendrites always showed extensive plasmalemmal juxtapositions with one or more unlabeled perikarya. The apposed perikarya had round nuclei and other characteristics of medium, spiny neurons. The majority of the apposed cholinergic and non-cholinergic neurons were postsynaptic to at least one common unlabeled terminal. These terminals usually formed symmetric junctions. At sites of appositions, the plasmalemmas of choline acetyltransferase-immunoreactive soma or dendrites and unlabeled neurons were closely spaced without intervening astrocytic processes. The appositions lacked the ultrastructural features typical of gap-junctions, but did occasionally show parallel arrays of thin (1-2 nm) electron-dense bands. In both labeled and unlabeled perikarya, the nuclei were separated from the appositional zones by narrow (0.7-3.3 microns) rims of cytoplasm. This cytoplasmic rim contained subsurface cisternae and other less specialized smooth and rough endoplasmic reticulum, and vesicular structures. The findings suggest that in the caudate-putamen nuclei (1) the tonically active cholinergic neurons [Wilson C. J. et al. (1990) J. Neurosci. 10, 508-519] may modulate or be modulated by non-cholinergic spiny neurons through non-synaptic somatic or dendritic appositions, and (2) that both neurons may be simultaneously inhibited by shared afferent input. Activation of this system could facilitate coordinated movements through synchronization of cholinergic interneurons and spiny projection neurons containing GABA or other transmitters. PMID- 1870701 TI - Effects of locus coeruleus lesions on parkinsonian signs, striatal dopamine and substantia nigra cell loss after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in monkeys: a possible role for the locus coeruleus in the progression of Parkinson's disease. AB - Six pairs of female squirrel monkeys were given a daily intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 9-14 days, beginning the same day on which they received either a bilateral 6-hydroxydopamine lesion or a sham lesion of the locus coeruleus. Sham animals developed typical parkinsonian signs (i.e. tremor, bradykinesia, hypokinesia and reduced blink rate) which largely recovered by six to nine weeks after the start of MPTP treatment. At nine weeks, post mortem levels of striatal dopamine in these same animals were partially reduced (by 45%), and this only in the putamen, compared to values obtained from three non-operated, normal control animals. Additionally, histological examination revealed a moderate loss of neuronal cell bodies in the substantia nigra, pars compacta. In marked contrast, the locus coeruleus-lesioned monkeys exhibited little or no recovery from the parkinsonian signs induced by MPTP. Post mortem examination of these animals revealed profound decreases in caudate (by 84%) and putamen (by 91%) dopamine content, and severe neuronal cell loss in the substantia nigra pars compacta of all animals. These neurological, biochemical and histological assessments indicate that lesioning of the locus coeruleus impairs the recovery which usually occurs from the parkinsonian manifestations induced by MPTP in squirrel monkeys. The results support the hypothesis that deficient locus coeruleus noradrenergic mechanisms underlie the progression of Parkinson's disease. PMID- 1870702 TI - Effect of harmaline on cells of the inferior olive in the absence of tremor: differential response of genetically dystonic and harmaline-tolerant rats. AB - The genetically dystonic rat is insensitive to the tremorogenic effects of harmaline. This behavioral deficit has been linked to a defect in the olivocerebellar pathway, since few Purkinje cells of dystonic rats show a normal increase in rhythmic complex spike activity following harmaline. In normal rats, the Purkinje cell response to harmaline and tremor are initiated by a rhythmic increase in neuronal firing in the caudal inferior olive. The present single unit recording study was conducted, therefore, to determine if the inferior olive of the dystonic rat is activated by harmaline. Olivary unit responses to harmaline were also examined in normal rats made tolerant to harmaline tremor. These rats are behaviorally insensitive to harmaline and also fail to display rhythmic complex spike activity but do not have the motor deficits of the mutant rats. The spontaneous firing rate of neurons in the caudal and rostral inferior olive of the dystonic rat was significantly slower than that of phenotypically normal littermates. Despite this, all cells recorded in the caudal portion of the medial accessory olive of both dystonic and normal rats showed increased rhythmic activity following harmaline injection. Thus, the failure of the mutants to show harmaline tremor is not due to a failure of the drug to activate cells in the olive. Rather, the data suggest a defect in the subsequent transmission of this information. Unlike the control and dystonic rats, harmaline-tolerant rats failed to show sustained rhythmic activity in the inferior olive. These findings suggest that chronic treatment with harmaline may interfere with harmaline tremor at the level of the inferior olive. PMID- 1870703 TI - Functional activity mapping of the rat spinal cord during formalin-induced noxious stimulation. AB - The functional activity pattern in the cervical enlargement of the spinal cord (as expressed by changes in local glucose utilization) was investigated by the semi-quantitative [14C]2-deoxyglucose technique 2 min ("early" group) or 60 min ("late" group) after injection of a small amount of dilute formalin (0.06-0.08 ml, 5%) in a forepaw of unanesthetized, freely-moving rats. Control animals were either injected with an equivalent volume of saline or simply handled. In both formalin groups a tonic flexion of the injected limb was present during the experiments, while supraspinal-integrated behavior (such as licking the affected paw) was sharply reduced in the late group. A bilateral increase of metabolic activity indexes, more pronounced on the ipsilateral side, was found in the "early" formalin-injected animals. The highest increase over control values was found in the medial part of the superficial (laminae I-II) region of the ipsilateral dorsal horn. However, the [14C]2-deoxyglucose uptake was found to be elevated over the whole extent of the dorsal horns, as well as in the gray matter surrounding the central canal, anterior horns and ipsilateral dorsolateral funiculus. In a parallel group of experiments performed in pentobarbital anesthetized rats metabolic increases in the early period after formalin injection were less pronounced; they were only found in the ipsilateral side of the cord. In the "late" formalin group the overall metabolic changes were less conspicuous. They were mainly observed in the side ipsilateral to the injection, the highest increase being found in the deep portion (laminae V-VI) of the dorsal horn. Therefore, the spatial distribution of functional activation elicited during prolonged noxious stimulation in the spinal cord gray matter of unanesthetized rats varies according to time and changes in animal behavior. PMID- 1870704 TI - Functional activity mapping of the rat brainstem during formalin-induced noxious stimulation. AB - Functional activity changes in 35 selected structures of the rat brainstem elicited by subcutaneous formalin injection in a forepaw were investigated by the [14C]2-deoxyglucose method in unanesthetized, freely moving animals. Experiments were initiated 2 min ("early" group) or 60 min ("late" group) after the injection. Treatment induced a significant increase of [14C]2-deoxyglucose uptake relative to controls in 17 structures of the "early" group, including portions of the bulbar, pontine and mesencephalic reticular formation, nucleus raphe magnus, median and dorsal raphe nuclei, the ventrolateral and dorsal subdivisions of the periaqueductal gray matter, deep layers of the superior colliculus and the anterior pretectal nucleus. Most changes were bilateral, with the exception of the increases observed in the nucleus reticularis paragigantocellularis and the lateral parabrachial area, which were contralateral, and the one in the mesencephalic reticular formation, which was ipsilateral to the injected paw. In pentobarbital-anesthetized rats a significant difference in metabolic activity values between formalin- and saline-injected animals was only detected at the medullary level. In the "late" unanesthetized formalin group functional activity levels were higher than controls in four structures, including the lateral reticular and paragigantocellular nuclei, contralaterally, and nucleus cuneiformis and ventrolateral periaqueductal gray matter, bilaterally. No between groups difference was observed in visual or auditory structures. These results provide evidence for activation of several brainstem regions, which are conceivably involved in different sensory, motivational or motor circuits, during the initial phase of formalin-evoked noxious stimulation in unanesthetized animals. Functional changes blunted over time as did pain-related behavior integrated at the supraspinal level, but they persisted in some brainstem regions for which involvement in endogenous antinociceptive systems have been suggested. The mechanisms underlying these time-related changes need to be clarified. PMID- 1870705 TI - Influences of central gray matter stimulation on thalamic neuron responses to high- and low-threshold stimulation of trigeminal nerve structures. AB - Responses of the thalamic non-specific medial nuclei and relay ventral posteromedial nucleus neurons evoked by stimulation of the teeth pulp of A alpha and A sigma fibers of infraorbital nerve and caudal nucleus of the spinal trigeminal tract were studied in cats under thiopental-chloralose anesthesia. Three groups of neurons were revealed: low-threshold, high-threshold and convergent. In medial nuclei, 29% of neurons formed the low-threshold group, 12% made up the high-threshold group and 59% were convergent. In the ventral posteromedial nucleus 47% of neurons formed the low-threshold group, 4% made up the high-threshold group and 49% were convergent. Ninety per cent of the medial nuclei neurons and 79% of the ventral posteromedial nucleus neurons responded to stimulation of the caudal nucleus spinal trigeminal tract. The conditioning central gray matter stimulation could suppress responses of low-threshold, high threshold and convergent neuron groups. In medial nuclei 100% of responses induced by stimulation of teeth pulp and A sigma fibers of the infraorbital nerve were completely suppressed and 86% of responses induced by stimulation of the A alpha fibers of the infraorbital nerve stimulation were also completely suppressed. In the ventral posteromedial nucleus 40% of responses induced by stimulation of teeth pulp and A sigma fibers of the infraorbital nerve were completely suppressed and 26.4% of responses induced by stimulation of the A alpha fibers of the infraorbital nerve were completely suppressed. Conditioning stimulation of the central gray matter suppressed responses evoked by stimulation of the caudal nucleus spinal trigeminal tract and in the most part neurons of the medial nuclei and neuron responses of the ventral posteromedial nucleus. The inhibitory influence of central gray matter stimulation on neuronal responses evoked by stimulation of the caudal nucleus spinal trigeminal tract shows that the central gray matter had a direct influence on the activity of thalamic neurons. PMID- 1870706 TI - Expression of neuronal intermediate filament proteins ON1 and ON2 during goldfish optic nerve regeneration: effect of tectal ablation. AB - Goldfish retinal explants were used to study optic tectum participation in the regulation of intermediate filament protein synthesis in retinal ganglion cells during optic nerve regeneration. Retinas were explanted at various times after removal of the contralateral optic tectum. The synthesis of the intermediate filament proteins ON1 and ON2 in the cultures was quantitated by labeling with [35S]methionine, followed by two-dimensional gel electrophoresis, autoradiography, and densitometry. Neuritic growth from the explants was quantitated based on fiber length and density. In retinal explants placed in culture after 23 days of optic nerve regeneration, the synthesis of ON1 and ON2 was reduced when the tectum had been ablated. In contrast, synthesis of these proteins in explants placed in culture at an earlier stage of regeneration was not affected by tectal ablation. At all time points tested, neuritic outgrowth from retinal explants was stimulated by tectal ablation. These findings indicate that the synthesis of the ON1 and ON2 intermediate filament proteins during regeneration is not directly regulated by axonal volume. Further, our findings suggest that interaction between growing axons and tectum is important for sustained expression of these proteins during the later stages of optic nerve regeneration. PMID- 1870707 TI - Normal cerebrovascular regulatory mechanisms are present in intracerebral neuronal transplants. AB - Local cerebral blood flow and local cerebral glucose utilization were measured using quantitative autoradiography in parallel groups of rats (n = 5-7) which 12 15 weeks previously had undergone limited unilateral ibotenate-induced lesion of the nucleus basalis magnocellularis, followed by implantation into ipsilateral neocortex of primordial basal forebrain cell suspensions. Surviving transplants were visualized by acetylcholinesterase histochemistry. Neither lesion alone nor the presence of a transplant produced significant side-to-side differences in either blood flow or glucose use in any of the 20 brain areas measured. Glucose use within the transplant was independent of the site of implantation. When sited in neocortex, glucose use in the transplant (66 +/- 4 mumol/100 g per min) was significantly lower than in the corresponding contralateral site (113 +/- 3 mumol/100 g per min), whereas when sited in subcortical white matter, glucose use (53 +/- 3 mumol/100 g per min) was significantly higher than in the contralateral side (29 +/- 4 mumol/100 g per min). In the host brain as a whole, the ratio of blood flow to glucose use ipsilateral to the transplant (m = 1.27, r = 0.88) was not significantly different from that of the contralateral side (m = 1.30, r = 0.94). This relationship was also observed within the transplanted tissue itself despite the fact that alkaline phosphatase histochemistry revealed a relative hypervascularization associated with the implantation site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870708 TI - Selective innervation of embryonic hippocampal transplants by adult host dentate granule cell axons. AB - Fragments containing different cytoarchitectonic fields were dissected out of late embryonic rat hippocampal primordia and transplanted into the hippocampus or septum of adult syngeneic hosts. Field CA3 transplants contained clusters of large, angular (pyramidal) cell bodies surrounded by a radiating corona of dendrites. These cells stained selectively with our monoclonal antibody Py, and a proportion were labelled by [3H]thymidine administered on the 15th day of embryonic life. Field CA1 transplants contained smaller, angular, Py-negative cells, which formed elongated laminae rather than globular clusters. The ability of the host dentate granule cells to project to the transplants was examined by (1) the Timm stain for mossy fibres, (2) electron microscopy of Golgi-impregnated CA3 pyramidal neurons in the transplants, and (3) quantitative electron microscopic assessment of the proportions of large mossy fibre terminals in the synaptic population of the transplants. The Timm stain showed that CA3 transplants received a projection from host dentate granule cells when the transplants were placed in direct contact with the axons in the host mossy fibre pathway. As in the normal host field CA3, the ingrowing mossy fibres terminated selectively on the juxtacellular regions of the dendritic tree and ignored the major part of the dendrites in the radiating corona. The electron micrographs showed that within this territory the host mossy fibres formed synaptic terminals with all the complex features typical of normal mossy fibres, and were presynaptic to complex spines arising from the juxtacellular region of Golgi impregnated donor CA3 pyramidal cells. The quantitative electron microscopic study demonstrated that the mossy fibre-innervated juxtacellular regions of the field CA3 transplants had up to 20% of the normal density of mossy fibre synapses found in the stratum lucidum of field CA3 in situ. CA3 transplants which were placed in the septum, remote from the host mossy fibres, had either trivial numbers of mossy fibre synapses or none. This confirmed that the abundant mossy fibre terminals in the intrahippocampal CA3 transplants were of host origin, and not due to donor dentate granule cells inadvertently included in the grafts. The selectivity of the host dentate projection for field CA3 transplants was demonstrated by the observation that CA1 transplants in the same locations received only slight mossy fibre projections in the Timm stain, and in electron micrographs their synaptic population had only insignificant numbers of large mossy fibre terminals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1870709 TI - Antibodies in the cerebrospinal fluid of some Alzheimer's disease patients recognize amoeboid microglial cells in the developing rat central nervous system. AB - Previous investigations have demonstrated that the cerebrospinal fluid from Alzheimer's disease patients contains antibodies that recognize specific neuronal populations in the adult rat central nervous system. These findings suggest a pathogenic role for immunological aberrations in this disorder. In the present report the investigation of antibodies in the cerebrospinal fluid of Alzheimer's disease patients was extended to developing rat central nervous system. The antibody in cerebrospinal fluid from Alzheimer's disease patients recognized entirely different types of antigens in the developing rat central nervous system as compared to adult rat central nervous system. One of the most remarkable differences was the recognition of amoeboid microglial cells. Diverse morphological forms of amoeboid microglial cells were observed, located mainly in the cavum septum pellucidum and in the corpus callosum. Electron microscopy revealed that the cerebrospinal fluid antibody from the Alzheimer's disease patients recognized specific membrane receptors in the macrophagic microglia. The unexpected recognition of amoeboid microglia by antibodies in Alzheimer's disease cerebrospinal fluid is particularly interesting since these cells proliferate in response to nervous system disease and also engulf debris. The results add further support to the concept that inflammation and similar immune mechanisms may contribute to Alzheimer's disease pathogenesis. PMID- 1870710 TI - Influence of imipramine on neuropeptide Y immunoreactivity in the rat brain. AB - The effects of treatment with the antidepressant drug imipramine on neuropeptide Y immunoreactivity were studied immunocytochemically in the rat brain cortex and hypothalamus. It was found that the level of neuropeptide Y immunoreactivity in the cortex was significantly lowered three and 24 h after the last dose of chronic (14 days) imipramine administration as well as 3 h after acute administration. A tendency to decrease neuropeptide Y immunoreactivity was also found in the hypothalamus. The results obtained suggest an important role of the cortical neuropeptide Y in the action of the drug. PMID- 1870711 TI - Effect of intracranial pressure on cerebrospinal fluid formation in isolated brain ventricles. AB - The effect of intracranial pressure on cerebrospinal fluid formation has been studied in cats by ventricular perfusion with the aqueduct of Sylvius blocked (isolated ventricular perfusion). It has been found that intracranial pressure has a considerable effect on the rate of cerebrospinal fluid formation, while increases in pressure cause a significant and prolonged decrease in cerebrospinal fluid formation. The effect was observed in animals whether they were initially perfused under lower or under higher intracranial pressure. Cerebrospinal fluid absorption has been studied under the above conditions and it has been noted that the ventricles are capable of significant cerebrospinal fluid absorption, since in isolated ventricles cerebrospinal fluid formation and absorption were in balance at physiological intracranial pressure. In addition, cerebrospinal fluid formation rate within the isolated brain ventricles has been compared with the formation rate in the whole cerebrospinal fluid system. Since only about 30% of the total cerebrospinal fluid formation was observed by isolated ventricular perfusion, it seems that the brain ventricles are not the exclusive site of cerebrospinal fluid formation. PMID- 1870712 TI - Ontogenesis of neocortical asymmetry: a [3H]thymidine study. AB - Previous research has demonstrated that symmetric regions in one brain are, on the whole, larger than their asymmetric counterparts in another brain, and that side differences in the volumes of homologous architectonic areas are the result of a decrease in neuronal number in the smaller of the two areas. Therefore, understanding mechanisms by which neuronal numbers are regulated during development may be essential to the investigation of the ontogeny of asymmetry. The radial unit hypothesis of Rakic postulates four factors that determine the number of neurons within a neocortical region: (i) early progenitor cell division; (ii) late cell division; (iii) the effect of thalamocortical and corticocortical afferents, which govern, in part, boundary placement; and (iv) ontogenetic cell death. We report here on experiments that address the development of anatomical asymmetry in the light of this hypothesis. Pregnant Wistar rats were injected with [3H]thymidine on several dates during embryogenesis and their pups killed at several postnatal ages. An estimate of the total number of neurons contained within area 17 and area 18a of each hemisphere was determined and the percentage of those which were labeled was calculated. There were no side differences in this measure between either symmetric or asymmetric architectonic areas although there were consistent differences between areas 17 and 18a. This indicated that while late neuroblast division may be important for cytoarchitectonic differentiation, it may play little or no role in interhemispheric asymmetry. PMID- 1870713 TI - Synaptic noise in spike trains of normal and denervated electroreceptor organs. AB - The sequence of interspike intervals of the spontaneous activity in denervated electroreceptor organs of the catfish is analysed with several statistical techniques: visual inspection of dot displays, interval histograms, serial correlograms, tests for stationary and trends, and tests for renewal properties, based on the spectrum of intervals. The interspike interval train of primary afferents can usually be treated as a renewal process. Following denervation, a number of non-renewal properties emerge. The interval histogram of the renewal spike trains can be fitted well with a gamma probability density function; non renewal cases need a more complex approach. We propose that the stochastic fluctuations in interval duration arise from randomly occurring quantal depolarizations (Stein's model of stochastic neuronal excitations. Two important properties with regard to synaptic transduction are: afferent firing results from capture of a limited number of depolarizing quanta; and the quantal input rate and the threshold for firing appear to be correlated. PMID- 1870714 TI - The supraoptic nucleus in hypothyroid and undernourished rats: an experimental morphometric study. AB - The supraoptic nuclei of both male and female 30-day-old rats rendered hypothyroid by daily subcutaneous injection of propylthiouracil were studied and the results were compared with age- and sex-matched rats fed ad libitum (control rats) and with undernourished rats. Morphometric methods were used to evaluate the volume of the supraoptic nucleus and the areal and numerical densities of its neurons. These parameters allowed us to estimate the total number of neurons of this nucleus. In addition, the mean cross-sectioned area and mean nuclear diameter of the same neurons were also evaluated. The volume of the supraoptic nucleus was reduced both in hypothyroid and undernourished animals when compared with normal controls. The areal and numerical densities of neurons from the former groups were increased and the volume density of the neuropil was reduced. As a consequence, the total number of neurons was found to be identical in all groups studied. Furthermore, the mean nuclear diameters and cross-sectioned areas of the supraoptic neurons were similar in all groups. The volumetric differences and the increased packing found were always more marked for hypothyroid than for undernourished rats. Differences were not detected between male and female groups. The present results support the view that the increased cell packing in hypothyroid animals depends upon a reduction in the neuropil of the nucleus, as has been described under similar conditions in other central nervous system areas displaying identical patterns of neurogenesis. In addition, it was found that the effects of undernourishment cannot be discriminated from those dependent on neonatal hypothyroidism. PMID- 1870715 TI - Patterns of brain infarctions in internal carotid artery dissections. AB - In 15 patients with internal carotid artery (ICA) dissections, patterns of brain infarctions visible on CT were categorized according to a pathogenetically oriented classification system. This differentiated ischemic brain damage due to low flow from thromboembolic infarctions. Simultaneously, cerebral hemodynamic reserve was evaluated by means of both CO2-dependent vasomotor reactivity and HMPAO- and 99mTc-RBC-SPECT. Six out of 11 patients with ischemic infarctions had the territorial type of brain lesion, suggesting distal embolism. Five patients revealed the pattern of hemodynamically induced low-flow infarctions. Cerebral hemodynamic reserve was significantly decreased only in these latter patients. In ICA dissections the frequencies of hemodynamically and thromboembolically induced brain infarctions is approximately equal. This finding suggests that only half of the patients with symptoms of symptomatic dissections had brain emboli, whereas in the other half the dissections lead to a low-flow effect in terminal supply areas which is so severe that non-embolic brain infarctions occur. This differentiation can help decide whether antithrombotic or hemodynamic treatment should be given. PMID- 1870716 TI - Long term prognosis of symptomatic and asymptomatic cerebral aneurysms. AB - The authors analyze the follow-up series of 58 patients with diagnosed cerebral aneurysms who were either not treated surgically or, in surgically treated cases, in which the aneurysmal neck was not clipped. The patients are divided in three groups: untreated ruptured; ruptured treated by coating, vessel ligation or aneurysmal dome clipping; and asymptomatic cases. During the follow-up period of three to ten years, there were no bleedings from asymptomatic aneurysms and only one rebleeding from symptomatic operated aneurysms. As can be expected in the group of ruptured unoperated aneurysms, the rate of rebleeding was 40.9% with a mortality rate of 31.7%. The natural history of asymptomatic aneurysms is unclear regarding the risk of bleeding, and regardless of the obtained follow-up results in our cases, we think that all diagnosed cerebral aneurysms must be treated surgically. Certainly, individual cases must be evaluated. PMID- 1870717 TI - Kluger's "fixateur interne" for spinal instability. AB - Kluger's "Fixateur Interne" proved to be an excellent tool not only in spinal trauma for repositioning of impacted fractures and transpedicular stabilization of the dorsal column but also in other forms of thoracic or lumbar instability. After spinal tumor excision from a dorsal approach and vertebral replacement with methylmethacrylate additional stability through dorsal fixation was achieved with this device. Spondylodiscitis, symptomatic spondylolisthesis, spinal instability from degenerative disc disease as well as "non-union" following previous surgery could be cured using Kluger's internal fixation. Rare complications, i.e. from broken screws or rods (5%) caused no problems, but some patients required a second operation for readjustment of malpositioned screws which were causing pain or neurological deficit. PMID- 1870718 TI - Tumors of the lateral ventricles. AB - Tumors are only rarely found in the lateral ventricles. Although various oncotypes of these tumors differ in growth rate and invasiveness they present the same clinical pattern with the same diagnostic and surgical problems. Thus we can consider them as a group. This series comprises 51 primary tumors arising strictly from the structures of the lateral ventricles, the majority from the trigone, operated on between 1952 and 1988: 20 meningiomas, 19 ependymomas, 9 papillomas of the choroid plexuses, and 3 subependymomas. As most of these tumors were benign, the response to surgical treatment was, as other authors have found, good with permanent cure or long survival in the majority of cases. Advances in neuroradiological techniques have greatly facilitated the work-up and differential diagnosis of these tumors. Of the various surgical approaches, the parieto-occipital is preferred by our department, even for tumors of the dominant hemisphere. Our operative mortality of 10.6% tallies with that of other workers. PMID- 1870719 TI - Cerebellar medulloblastomas in adults. AB - A retrospective analysis of 32 patients older than 16 years of age treated at Neurosurgical Department of Hacettepe University within the last 30 years (1959 1988) for cerebellar medulloblastoma was considered. The clinical features, treatment modalities and outcome are discussed. The survival rates for 5 and 10 years were 14% and 7% respectively. The results are compared with that of literature. PMID- 1870720 TI - CSF hydrocele--unusual complication of V-P shunt. AB - CSF hydrocele as a complication of migration or extrusion of the peritoneal end of the V-P shunt has rarely been reported. Here the case of a 6 month old infant, born at 28 weeks gestational age, is reported. The baby was noted to have scrotal swelling, exacerbated by crying, two months after insertion of ventriculoperitoneal shunt. The hydrocele resolved following revision of the shunt. Possible pathophysiological causes are discussed. PMID- 1870721 TI - Diagnosis and treatment of deep cerebral vein thrombosis. AB - Three cases of deep cerebral vein thrombosis are reported. In all three cases focal neurological deficits and impaired consciousness occurred after a short period of non-specific clinical manifestations. Computed tomography revealed bilateral hemorrhagic infarctions of thalamus and basal ganglia. The CSF analysis which was performed in two cases showed pleocytosis, increased protein level, disturbed blood-brain barrier, and signs of necrosis and hemorrhage. In two cases the diagnosis was confirmed by transfemoral carotid angiography. MRI was performed in one case only and showed thrombosis of the internal venous system. All patients were treated with high-dose heparine in spite of hemorrhage. Good recovery was seen in all patients with almost complete improvement of neurological deficits. No complications were observed during treatment. Because of these promising therapeutic results, bilateral thalamic lesions should alert the physician to consider the possibility of deep cerebral vein thrombosis. PMID- 1870722 TI - Duplicated peritoneal catheter as a cause of shunt malfunction. Case report. AB - A rare example of ventriculo-peritoneal shunt malfunction is presented. Radiological and operative findings demonstrated a self-duplication with upward migration of the peritoneal catheter. PMID- 1870723 TI - The clinical role of PET in cerebrovascular disease. AB - In normal subjects cerebral oxygen metabolism and blood flow are closely coupled, both grey and white matter extracting about 40% of their arterial oxygen supply. During acute ischaemia blood flow falls and oxygen extraction rises to 100% so that cerebral metabolism becomes totally blood flow dependent. Once acute infarction has occurred both cerebral oxygen metabolism and arterial oxygen extraction fall to low levels, while blood flow often paradoxically rises--the state of luxury perfusion. Once luxury perfusion becomes established the use of pharmacological or surgical methods to increase cerebral blood flow is inappropriate. PET will measure regional cerebral metabolism and blood flow non invasively in man. Using PET ischaemic tissue can be distinguished from infarcted tissue, and the presence of luxury perfusion can be confirmed. In this way strokes in evolution can be detected, and the use of revascularisation procedures rationalised. Not only are regional cerebral metabolism and blood flow closely coupled, but blood volume is also coupled to blood flow. When greater than 60% stenosis of extracranial arteries occurs, reactive vasodilation of the distal circulation with an increase in rCBV results in order to reduce vascular resistance. By monitoring rCBV with PET, haemodynamically compromised regions of brain can be detected. It has been shown that patients with local areas of raised rCBV due to carotid artery stenosis are at a higher risk of infarction. PET will identify such patients and follow the haemodynamic effects of endarterectomy or EC-IC bypass. Finally PET can look at the distant functional effects of lacunar infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870724 TI - Neuropeptides. AB - This review summarizes the revolutionary impact of brain peptides on our understanding of the nervous system and then discusses the localization, distribution, synthesis, receptor sites, and possible function of 32 brain peptides. The peptides are discussed in three subgroups: I) the opioid peptides, which include beta-endorphin, the enkephalins, and dynorphin; II) the pituitary releasing hormones, most of which are wide-spread in the brain and include corticotropin-releasing hormone, luteinizing hormone-releasing hormone, somatostatin, and thyrotropin-releasing hormone; and III) a selection of 12 other peptides potentially important for neurological function, including vasopressin, oxytocin, substance P, cholecystokinin, bombesin, neurotensin, renin, angiotensin, vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene related peptide, and calcitonin. Within each individual peptide section, the possible physiological roles in anterior pituitary hormone release, blood-flow regulation, feeding behavior, temperature regulation, nociception, memory and learning, and movement are reviewed. Further, where noted, the peptide findings in Huntington's, Alzheimer's, Parkinson's and psychiatric diseases are emphasized. PMID- 1870725 TI - [The need for "intermediate" intensive care units. Epidemiologic study in a metropolitan area]. AB - 2710 patients were admitted during 1988 to 14 ICU of a crowded urban area. No Intermediate ICU facilities were available. We determined the need and the likely patient turnover of such an ICU. 29% of the admitted patients and 9% of the days spent in the ICU would be due of an sub-intensive ICU (only 60-30% of the expected turnover) and 54% of the admitted patients (70% of the intensively treated patients) would be feasible for the post-intensive-ICU. 82% of the case mix would be admitted by the intermediate ICU with a length of ICU stay 21-28% of the total stay. 56-68% of this time spent in intermediate ICU would be utilized by post-intensive patients. The increased patient turnover would allow the admission of 566-806 intensive patient/year that means the most urgent need in ICM today is to increase the number of intermediate ICU. PMID- 1870726 TI - [Atracurium as an alternative to succinylcholine in oro-tracheal intubation]. AB - Intubation conditions were considered in 75 patients undergoing gynecologic surgery following intravenous administration of suxamethonium (1 mg/kg-1) or sequence atracurium (0,5 mg/kg-1)-thiopentone. A statistically significant difference of intubation depth of neuromuscular blockade was found between the groups, but the tracheal intubation was performed within 60 sec following the intravenous injection of the two muscle relaxants in all patients. Intubating conditions were scored as excellent in 67 cases, good in 5 cases and poor in 3 cases. Cardiovascular stability was relieved. PMID- 1870727 TI - [Pressure changes in the middle ear during nitrous oxide anesthesia]. AB - We studied middle ear pressure variations in 17 patients with mild upper airways or middle ear diseases, during nitrous oxide anaesthesia. We observed a significant increase in middle ear pressure during the administration of nitrous oxide, and a significant decrease after nitrous oxide was discontinued. Nine patients showed periodical reductions of the middle ear pressure during the inhalation of nitrous oxide, due to passive openings of the eustachian tube. In the remaining 8 patients (47%) this mechanism has not been effective. A comparison between these two groups shows significantly higher levels of middle ear pressure in the group of patients with abnormal function of the eustachian tube, both during and after the administration of nitrous oxide. Our results demonstrate that patients with mild upper airways or middle ear diseases are likely to show an impaired tubal function. Therefore, nitrous oxide should be used with caution in the presence of such diseases. Moreover, nitrous oxide is generally controindicated in middle ear surgery, as the pressure gradients between middle and external ear can jeopardize the success of the operation. PMID- 1870728 TI - [Loss of plasma protein in open-heart surgery]. AB - The changes in the concentrations of nine serum proteins were studied in ten patients who underwent open-heart surgery for mitral or aortic valve replacement. alpha 1-glycoprotein, albumin, transferrin, alpha 2-macroglobulin, IgG, IgA, IgM, C3, and C4 were assessed before anesthesia induction, after sternotomy, ten minutes after the beginning of CPB, and ten minutes following the end of CPB; values were corrected for haemodilution. All the proteins, with the exception of alpha 1-glycoprotein, showed similar trends that were characterized by a significant decrease after CPB. Linear contrasts did not show any significant difference among the proteins expressed as per cent of the initial values. Such generalized decrease was probably due to the aspecific damage caused by oxygenators, pumps and aspirators. On the contrary, specific mechanisms, as IgM aggregation or complement activation, do not affect significantly the concentration of single proteins. Also the hypothesis of a relevant protein migration toward the extravascular space was rejected because of the absence of any significant relation between the molecular weight of the proteins and their decrease after CPB. PMID- 1870729 TI - [Continuous monitoring of mixed venous oxygen saturation during mechanical circulatory support of the left ventricle in heart surgery patients. Pathophysiologic principles and personal experience]. AB - The clinical use of mechanical supports for cardiocirculatory function assistance has permitted to treat a higher number of low output syndromes insensitive to pharmacological therapy. One of the most important problems arising during mechanical circulatory assistance, is the ability to know if the performance of the artificial device is adequate to match metabolic tissues demands. Continuous monitoring of mixed venous O2 saturation (MSvO2) has been proposed as the most complete and reliable tool to verify this correlation. The Authors analyse the problems connected with this kind of monitoring during left ventricular assistance with centrifugal pump in cardiosurgical patients and present 6 cases taken from their clinical experience. PMID- 1870730 TI - [Effectiveness of regional anesthesia for loco-regional carotid surgery. Retrospective review of 147 interventions]. AB - The Authors present a retrospective review that compares general anesthesia with regional anesthesia performed during carotid endarterectomy surgery. The study includes 147 procedures, performed on 144 patients: 76 had general anesthesia and 71 had regional anesthesia. After emphasizing the importance of conscience preservation during regional anesthesia to allow a simple and secure monitoring of the patient's neurologic functions, the Authors point out the decrease of peri and postoperative accidents, whether neurologic or not, obtained with regional anesthesia. Another essential advantage of this technique is the possibility to insert the transitory shunt only when objectively necessary, ulteriorly reducing neurologic complications. Cervical plexus block is primarily indicated for high risk patients with instable neurologic simptomatology, severe stenosis of the contralateral carotid, coronary heart disease. The technique has proved to be of easy execution, safe and well accepted by the patient and the surgeon. PMID- 1870731 TI - [Kinetic study during amino acid infusion in catabolic patients. Comparison between two solutions]. AB - The equilibrium kinetic of two different amino acid solutions was investigated in ten catabolic patients (Parentamin, Pierrel; HBC, Baxter). Plasma amino acid pattern was determined on arterial samples before TPN and several times over 48 hours of TPN. Nitrogen balance was measured from 24 hours urine collection. Three different cinetic trends were found: a fast modification (diminution or increase), a slow adaptation, or no modification of plasmatic levels, however each amino acid reached a steady state plateau. The adequacy of the infusion of each amino acid was evaluated comparing its steady-state plasma level to the after lunch level in healthy man. This made possible to approximate metabolic needs of each of the infused amino acids and to identify the inadequacy of some metabolic pathways to synthetized non essential amino acids lacking in solutions. This made possible to identify amino acids infused in excess or in defect, and those infused in dose adapt to the metabolic needs of such patients. PMID- 1870732 TI - [Clinical evaluation of propofol-ketamine anesthesia in general surgery]. AB - The combinations propofol-ketamine vs propofol-fentanyl in absence of N2O was compared in 60 patients undergoing abdominal surgery. The results show that ketamine and fentanyl provide a good analgesia in the absence of N2O and that ketamine offers better haemodynamic control. PMID- 1870733 TI - [Isolated persistent left superior vena cava. Detection of cause during central venous catheterization]. AB - The Authors report the causal discovery of isolated persistent left superior vena cava (IPLSVC) during a central venous incannulation with a Groshong's catheter, in a patient undergoing bone marrow transplant. After a short introduction about the IPLSVC ontogenesis, they stress the need for fluoroscopy during the central venous incannulation. The Authors conclude that the possibility of angiocardiography has been very helpful, in this case, for diagnosis and prognosis. PMID- 1870734 TI - [Thymoma: anatomo-clinical and therapeutic aspects. Analysis of our 26 cases]. AB - The paper reports the authors' personal experience with regard to 26 cases of thymoma treated surgically over the past 10 years. 96% of cases were associated with myasthenia gravis. Surgery was performed in all cases and 13 cases (50%) underwent additional RT. 92% of patients were affected by invasive thymoma (11 stage II cases, and 13 stage III). From an histological point of view, 38.5% of cases were epithelial-type thymomas, 38.5% were lymphoepithelial and 23% were lymphocytic. Survival was influenced by the stage of disease and the radicality of surgery. At present, 76% of patients are still alive between 10 months and 10 years of surgery. There was a perioperative mortality of 11.5% (3 cases), whereas 2 patients died some 2 months later due to pulmonary embolism. The paper also includes a critical review of the most recent literature, and the authors compare their experience with that of other centres. PMID- 1870735 TI - [Acute thyroiditis]. AB - Acute suppurating thyroiditis is now an uncommon pathology which is rarely found, although it was frequent before the introduction of antibiotics. Having observed a case, the Authors were prompted to study the subject in greater depth, in particular to assess whether the disease is easier to diagnose using modern techniques diagnosis, and whether there are changes in the therapy. In conclusion, the paper affirms that in spite of the fact that the diagnostic evolution has thrown further light on the clinical aspects of the disease, biopsy still remains the most reliable instrument of diagnosis, whereas surgery is the most effective form of therapy. PMID- 1870736 TI - [Microbiological analysis of postoperative infectious complications]. AB - A variation among the strains responsible of nosocomial infections was noted in the last years with a revival of Gram + bacteria. Coagulase-negative staphylococci assumed a great importance, particularly those resistant to methicillin. Staphylococcus epidermidis is now an important infective agent, especially in patients with prostheses or other devices. To value the impact of these microbiological variations on surgical patients, we studied data related to 1271 specimens from postoperative septic complication from 1980 to 1988. The incidence of Gram + strains in surgical infections was 46.8% in 1980-1983 period and 59.2% in 1984-1988 period with statistical significance (p less than 0.05). PMID- 1870737 TI - [Contact thermography in breast pathology. A critical review]. AB - The paper reports the Authors' experience in over 12,000 patients affected by manifest or presumed breast pathologies examined using contact thermography and assess the number of correct responses. This technique proved reliable in patients aged under 30 with benign pathologies or palpable nodules. On the other hand, it was not reliable in the case of pathologies with negative objectivity, and therefore in the context of screening programmes for the early diagnosis of tumours. PMID- 1870738 TI - [Diagnosis of breast carcinoma. Comparison of clinical, mammographic, echographic and cytological aspiration diagnosis in a group of 50 patients]. AB - The study assesses the sensitivity of clinical, mammographic, echographic and needle biopsy tests in a sample group of 50 women some of whom were examined and operated by the Surgical Division of Casalpusterlengo Hospital, whereas others were examined and operated at Crema Hospital. Data were compared with those from larger studies recently reported in the literature. Patients had a minimum age of 42 years and a mean age of 64.3 years; all were symptomatic. Clinical examination, mammography and echotomography showed an increased sensitivity in parallel with the increased size of tumour and the patient's age. The sensitivity of mammography in T1 cases was higher than that of clinical examination and ultrasound tests. Diagnosis was made on cytological grounds alone in 2% of cases, but was negative in 14% (benign/inadequate sample) in spite of the presence of a positive clinical examination and mammography. A 90.4% sensitivity rate was achieved using a combined clinical examination and mammography. PMID- 1870739 TI - [General surgeon and breast reconstruction after mastectomy]. AB - Breast reconstruction is widely used in patients who have undergone mastectomy for breast cancer. The paper underlines that reconstruction is often performed by the general surgeon who has become an expert in this type of plastic surgery. The Authors present their own clinical data, and describe the indications and techniques used, and the results obtained. In conclusion, it is stressed that ideally the same surgeon should be experienced in oncology and plastic surgery. PMID- 1870740 TI - [Peri-inguinal hernia: classificatory inclusion. Considerations on rarity of the occurrence. Personal case reports]. AB - Peri-inguinal and Para-inguinal hernias are included in the group of lateral ventral hernias and must be distinguished from Spigelian and intraparietal ascending inguinal hernias. Peri-inguinal hernia is very unusual in its location and development. Non one similar case has been reported in literature. PMID- 1870741 TI - [Endoscopic retrograde cholangiopancreatography in biliary diagnosis. Critical review of the literature and presentation of personal experience]. PMID- 1870742 TI - [Pyloric stenosis caused by gallstone (Bouveret's syndrome). Presentation of a further case]. AB - The Bouveret's syndrome is a rare complication of a bilio-digestive fistula, where a big stone occludes the pyloro-duodenal region. The clinical symptomatology is atypical, symptoms of the disease are acute and only in fifty per cent of cases it is possible to have a positive anamnesis for biliary lithiasis. The evolution of the occlusion is generally rapid. The clinical case we are in possession of, shows a particularly chronic evolution with a 15 month sub-occlusive symptomatology that caused a massive gastric dilatation. The diagnosis of Bouveret syndrome was set forth during operation, as generally happens in about 50% of cases. The surgical treatment is still the only one capable to solve the obstruction of the alimentary canal and the bilio-digestive fistula at the same time. PMID- 1870743 TI - [Endoscopic treatment of postoperative external pancreatic fistula by means of papillotomy and naso-pancreatic drainage]. AB - External pancreatic fistula is a common complication after pancreatic resection. We report a case successfully treated by endoscopic papillotomy and a naso pancreatic tube. PMID- 1870744 TI - [Malignant schwannoma of the mesentery. Presentation of a clinical case and clinical and histopathological considerations]. AB - A case of malignant schwannoma of the mesentery is described which was treated with radical surgery. The natural history, diagnosis and therapy of neoplasias of the mesentery are discussed. PMID- 1870745 TI - [Rokitansky-Mayer syndrome: correction of total vaginal agenesis using partial skin graft]. AB - The Mayer-Rokitansky syndrome is a spectrum of mullerian anomalies, including vaginal agenesis with or without renal anomalies, in genotypic and phenotypic female subjects with normal endocrine status. We describe the management of a patient with this syndrome. We also propose a modified corrective method of the vaginal agenesis by a partial skin grafting. PMID- 1870746 TI - Does lead play a role in the development of chronic renal disease? AB - For many decades lead has been considered to be one of the causes of chronic renal failure. A critical analysis of the available epidemiological studies, however, indicates that the relationship between lead exposure and the development of chronic renal failure is largely circumstantial. Indeed, several aspects remain obscure: relative and absolute risk, risk factors, duration of exposure, pathology and diagnostic criteria. Moreover, methodological problems related to cohort selection (i.e. the 'Healthy worker effect'), study design and definition of renal dysfunction may limit the value of the epidemiological results. Although the available literature suggests that lead may play a direct or contributory role in the development of chronic renal failure it is concluded that additional detailed epidemiological studies are required. PMID- 1870747 TI - Glomerular epithelial cell endocytosis of immune deposits in human lupus nephritis. AB - Sixteen human renal biopsies taken from patients suffering from systemic lupus erythematosus nephritis were examined using an immunohistochemical method which allows the localisation of IgG at both light and electron-microscopical levels. The tissue was embedded in the hydrophilic resin lowicryl K4M and sections were stained using gold-labelled antibodies. On routine light microscopical examination the biopsies were diagnosed as: 1 case of WHO type II, 3 type III, 9 type IV, 2 type V, and 1 type III/V. Using light microscopy, IgG was localised in the glomerulus using the IGSS staining method. In some cases staining was seen within the glomerular epithelial cell cytoplasm. At the ultrastructural level the presence of IgG was demonstrated within vesicles in the cytoplasm of the epithelial cells in 0/1 type II, 2/3 type III, 8/9 type IV, 1/2 type V, and 1/1 type III/V cases: in some vesicles deposits of immune material were electron dense but in others immune material was electron-lucent. Our results suggest that the human glomerular epithelial cell can endocytose IgG and that this may be part of a clearance mechanism acting within the glomerulus. PMID- 1870748 TI - Effects of a two-month treatment with low oral doses of cyclosporin on renal function. AB - To test the effects of short-term therapy with low doses (LD) of cyclosporin A (CsA) in subjects with normal renal function, seven patients receiving CsA to treat psoriasis were studied. Clearances in maximal H2O diuresis were performed to evaluate changes in GFR (CIn), RPF (CPAH) and tubular function before starting CsA (BAS), after 2 days (S1) and 1 month (S2) of oral therapy with 5 mg/kg per day CsA. The study was repeated at the withdrawal of CsA after tapering (S3) and 2 months after the withdrawal (S4). The studies were performed 12 h after the evening dose of CsA. RPF was significantly less than in BAS throughout the therapy and returned almost to basal values in S4. GFR was significantly less than in BAS both in S2 and in S3. In S4, in spite of an increase, GFR was still significantly less than in BAS. Both in S2 and in S3 proximal tubular fractional sodium reabsorption was significantly less than in BAS and, consequently, both sodium delivery to diluting segments and sodium reabsorption in diluting segments increased. Moreover, both in S2 and in S3 fractional sodium reabsorption in diluting segments and free-water generation were greater than in BAS. In S4 tubular function returned almost to basal values. Our data suggest that short term therapy with low dose CsA impairs renal function; this impairment is not completely reversed after drug withdrawal. PMID- 1870749 TI - Advantage of early initiation of aluminum hydroxide administration for the prevention of experimental progressive renal disease. AB - Aluminium hydroxide, a phosphate binder, is regarded as a strong candidate to halt the progression of chronic renal disease. In order to determine the most effective time to start treatment, aluminium hydroxide was administered either immediately (ADR-0w), or at 8 weeks (ADR-8w) or 16 weeks (ADR-16w) after repeated injection of Adriamycin (ADR) inducing glomerular sclerosis. In the aluminium hydroxide-untreated group the survival rate at the end of the experiment was 50%, while the early initiation of aluminium hydroxide (ADR-0w) resulted in a greater survival rate of 90%. Serum phosphate concentration and serum calcium-phosphate product were significantly less in the aluminium hydroxide groups (ADR-0w, 8w, 16w) than in the untreated group after week 20. Urinary protein excretion was significantly less in the ADR-0w and ADR-8w groups at week 12 or 16 compared to the aluminium hydroxide-untreated group. Blood urea nitrogen in the aluminium hydroxide groups was significantly less than that in the untreated group at week 34. Histological examination revealed that glomerular sclerosis was less severe in the ADR-0w and ADR-8w groups than in the aluminium hydroxide-untreated group, and glomerular hypertrophy was significantly decreased in the ADR-0w group. We conclude that early treatment with aluminium hydroxide was effective in preventing renal deterioration in focal glomerular sclerosis induced by Adriamycin. PMID- 1870750 TI - The role of aluminium and parathyroid hormone in erythropoietin resistance in haemodialysis patients. AB - Recombinant human erythropoietin (rHuEpo) is an effective therapy for anaemia in most patients with end-stage renal disease (ESRD). However, there remain a minority of patients with ESRD who are resistant to the effects of rHuEpo. The present study examined the role of aluminium overload and hyperparathyroidism of the biological effects of rHuEpo. Twenty-two patients aged 26-74 (mean 53 +/- SD 15.5) received rHuEpo 50-200 U/kg per week for 16.5 +/- 8.0 months (range 3-27). Haemoglobin was maintained at 11.5-13.0 g/dl by appropriate dose adjustment. Iron supplements were provided to maintain serum ferritin greater than 200 ng/ml. The mean time to rHuEpo response (Hb greater than 2 g/dl over baseline) was 6.1 +/- 2.6 weeks. Mean pretreatment serum aluminium correlated with time to Hb response (r = 0.48; P less than 0.05) and pretreatment mean corpuscular volume (r = 0.43; P less than 0.05) but not with eventual rHuEpo maintenance dose. PTH did not correlate with either Hb response or eventual maintenance rHuEpo dose. In summary, elevated serum aluminium concentrations were associated with an initial resistance to the biological effects of rHuEpo but had no effect on long-term dose requirements. In contrast, no impact of PTH on either immediate or long-term rHuEpo dose was evident. PMID- 1870751 TI - Urine cytology as a screening method for transitional-cell carcinoma in dialysis patients with analgesic nephropathy. AB - The abuse of analgesic-containing drugs leads to chronic nephropathy with an increased risk of developing a transitional-cell carcinoma of the urinary tract. In our experience follow-up is often stopped or has never been started when patients present for dialysis. We use urine cytology as the screening method. Nine of the 138 patients entering dialysis between 1980 and 1990 had analgesic nephropathy. In three patients urine cytology led to a suspicion of malignancy. Cystoscopy and/or retrograde pyelography showed a carcinoma of the renal pelvis in two patients and a carcinoma of the bladder in one patient. The patients with carcinoma of the renal pelvis died of cardiovascular complications within 2 years of nephroureterectomy. An autopsy was performed in one of these patients and there were no residual tumours or metastases. In the other patient autopsy was not performed, but urine cytology again suggested malignancy. The patient with a carcinoma of the bladder is still alive. She was treated with transurethral resection of the tumour and etoglucide instillations. We conclude that urine cytology is a good screening method for the early detection of transitional-cell carcinomas in dialysis patients with analgesic nephropathy. PMID- 1870752 TI - Influence of first and long-term dialysis on uraemia-associated increased basal production of interleukin-1 and tumour necrosis factor alpha by circulating monocytes. AB - In a previous study we demonstrated the presence of circulating interleukin-1 (IL 1) in long-term haemodialysis patients and of tumour necrosis factor alpha (TNF alpha) in both long-term haemodialysis and not-yet-dialysed uraemic patients. The present report investigates the spontaneous capacity of monocytes to produce and secrete these two cytokines in 35 long-term haemodialysis patients and 36 uraemic patients undergoing their first dialysis session. Predialytic cell-associated IL 1 concentrations in freshly isolated monocytes were significantly increased both in long-term haemodialysis and first-dialysis uraemic patients compared to normal individuals. In both groups in comparison to normal individuals, although intracellular TNF alpha could not be detected in freshly isolated monocytes, both extracellular IL-1 and TNF alpha concentrations were greatly increased after 20 h of in vitro culture of monocytes in the absence of exogenous stimulation and in serum-free conditions. However, long-term haemodialysis patients showed higher values of secreted IL-1 than not-yet dialysed uraemic patients. During a single dialysis session a significant increase in both cell-associated and secreted IL-1 but not TNF alpha was observed in long-term haemodialysis patients. In contrast, no change in the concentration of either cytokine could be detected at the end of the first dialysis session in uraemic patients. Our findings strongly suggest that factors related to uraemia could be a sufficient signal to initiate intracellular IL-1 protein synthesis and TNF alpha release by monocytes, but that greater IL-1 release could be stimulated during the periodic haemodialysis procedure. PMID- 1870753 TI - Ultrasonography of renal allografts: collecting system dilatation and its clinical significance. AB - Reports and ultrasound scans (658 studies) of 135 renal allografts, transplanted in the years 1987 and 1988, have been reviewed. Records of the recipients were also studied in order to determine the clinical status of the kidney at the time of each ultrasound examination and to obtain long-term follow-up of allograft function. Seventy-seven allografts (57%) never showed pelvicalyceal dilatation on 342 serial examinations. Forty-two kidneys (31%) had mild dilatation reported on at least one scan, which did not progress. However, 11 mildly dilated allografts developed moderate to severe dilatation on later examinations and these, together with 5 allografts reported as exhibiting moderate to severe hydronephrosis on their first dilated scan, were classed as moderate to severe (n = 16 = 12%). Thirty-eight patients (90%) with mild dilatation of the collecting system had no evidence of obstruction. However, in allografts with moderate to severe dilatation and poor or deteriorating function, ten patients (70%) were found to have ureteric obstruction. There was no significant difference in 1-year graft survival (87% versus 81.8%) and the median serum creatinine at 3 and 12 months after transplantation between non obstructed 'dilated' and non-dilated allografts (149 mumol/l versus 153.7 mumol/l; 139 mumol/l versus 147.3 mumol/l). All 14 obstructed allografts were salvaged with a graft survival of 85.7% at 1 year. Median serum creatine in these patients was significantly elevated at 200 mumol/l and 189 mumol/l at 3 and 12 months; P = 0.05 and 0.01 compared to dilated non obstructed allografts. Our results indicate that grafts with moderate to severe dilatation should be urgently investigated to minimise further allograft damage. PMID- 1870754 TI - The effect of conversion from cyclosporin to azathioprine on renin-containing cells in renal allograft biopsies. AB - Renal biopsies were examined from 17 renal transplant recipients before and after conversion from cyclosporin to azathioprine, and in 17 patients who remained on cyclosporin. All patients had stable renal function. We used an immunoperoxidase technique with an antiserum to human renin to identify renin-containing cells. We demonstrated hyperplasia of renin-containing cells in patients treated with cyclosporin. Numbers of renin-containing cells decreased after conversion to azathioprine. We suggest that local activation of the intrarenal renin angiotensin system could mediate the effects of cyclosporin on renal haemodynamics. This could play a role in the pathogenesis of cyclosporin nephrotoxicity and cyclosporin hypertension. PMID- 1870755 TI - Successful treatment of severe lactic acidosis by haemofiltration using a bicarbonate-based replacement fluid. PMID- 1870756 TI - Magnesium in cyclosporin-treated kidney transplant patients. PMID- 1870757 TI - Continuous monitoring of blood pressure of patients on a haemodialysis programme. PMID- 1870758 TI - Two cases of recurrent focal and segmental glomerulosclerosis in renal allografts. PMID- 1870759 TI - NP unity impossible without reorganization of NANP. PMID- 1870760 TI - New screening guidelines for lead poisoning. PMID- 1870761 TI - Where's the nurturing and mentoring of new NPs? PMID- 1870762 TI - Assessment and prevention of osteoporosis through use of a client self-reporting tool. AB - Osteoporosis is an age-related process that affects one out of every four women above 65 years of age. This article focuses on the assessment of osteoporosis through use of an osteoporosis assessment tool that is filled out by the client. The tool requests information about the woman's demographic profile, chief complaint, related symptoms, pain profile, risk profile, past medical history, nutritional history, fitness profile, menopausal history and self-care practices. The tool also includes information for the health care provider to complete about the client's lab analysis. Assessment needs to be extensive in order to uncover the specific factors that place an individual at risk for the silent changes of osteoporosis. The health care provider can elicit the aid of the client in securing such a comprehensive assessment. PMID- 1870763 TI - Survivors of a family member's suicide: implications for practice. AB - Survivors of suicide are people who are coping with the loss of a loved one through an act of suicide. Primary health care providers are well-positioned to identify and intervene with this population, which is known to be at high risk for health disturbances. A research study was conducted to further clinicians' understanding of the experiences and needs of survivors. The major research question was, "What do adult survivors report about their perceived life experiences three to nine months after the suicide of a family member?" Data from audiotaped interviews with 35 adult survivors of suicide were analyzed to determine a description of the experiences and needs of this population. A recurrent theme discovered in the lives of survivors was the persistence of agonizing, unanswerable questions related to the death. Surviving family members struggled with why the suicide had occurred and worried about the impact of the death on themselves and others. Profound changes in the emotional, cognitive, physical and social functioning of survivors were also evident. Implications for clinical practice are discussed. PMID- 1870765 TI - Diagnosing rectal bleeding. PMID- 1870764 TI - The sensitivity, specificity and predictive value of diagnostic information: a guide for clinicians. AB - Nurse practitioners and other clinicians use laboratory studies and ancillary tests to confirm or rule out suspected conditions. Deciding which tests to use and interpreting results are essential to the practice of high-quality, cost effective primary care. A working knowledge of test characteristics and performance facilitates these decisions. This article illustrates how a conceptual understanding of sensitivity, specificity and predictive value applies to daily practice. In addition, the article explains how to evaluate the quality and relevance of literature that reports test performance. While discussion focuses on laboratory tests, the same principles may be applied to the history and physical examination, and to other types of diagnostic data. PMID- 1870766 TI - The face of an angel. PMID- 1870767 TI - Remembering Desert Storm. PMID- 1870768 TI - Choosing to say good-bye. PMID- 1870769 TI - Myths & facts ... about administering drugs. PMID- 1870770 TI - Disconnected epidural catheter. PMID- 1870771 TI - Getting the upper hand on lower extremity arterial disease. PMID- 1870772 TI - Adverse effects of chemotherapy. PMID- 1870773 TI - Correction for cardiac monitor. PMID- 1870774 TI - Alone out there. PMID- 1870775 TI - What you need to know about administering preoperative medications. PMID- 1870776 TI - A divided person, part nurse, part parent. PMID- 1870777 TI - Carol gave up fighting ... until her nurse stepped in. PMID- 1870778 TI - How to cope with under staffing. PMID- 1870779 TI - Performing clean, intermittent self-catheterization. PMID- 1870780 TI - Are you ready to use pulse oximetry? PMID- 1870781 TI - H.I.V. status. Mum's the word. PMID- 1870782 TI - Your guide to pediatric drug administration. PMID- 1870783 TI - Three golden hours. PMID- 1870784 TI - Pediatric patients. Finding the right words. PMID- 1870785 TI - The patient with lung cancer. PMID- 1870786 TI - Prevention--its time has finally come! PMID- 1870787 TI - ANA design criteria. PMID- 1870788 TI - A systems approach to the management of nursing services, Part VI: Costing system. PMID- 1870789 TI - Creating an environment to empower nurses. PMID- 1870790 TI - Professional governance: the missing link. PMID- 1870791 TI - Better communications make more compassionate hospitals. PMID- 1870792 TI - An epidural narcotics program for general care units. PMID- 1870793 TI - Nursing in space: a new frontier for nursing. PMID- 1870794 TI - Nurses' greatest fear: demise of the profession. PMID- 1870795 TI - A radical approach to current problems in nursing. PMID- 1870796 TI - The nature of nurturing. PMID- 1870797 TI - Effective peer review. PMID- 1870798 TI - Peer review board: one year later. PMID- 1870799 TI - Moving toward unity... PMID- 1870800 TI - Landry Guillain-Barre Strohl syndrome in pregnancy: report of three cases treated with plasmapheresis. AB - Landry Guillain-Barre Strohl syndrome complicating pregnancy is a rare occurrence, with only 31 cases previously reported in the obstetric literature. Cytomegalovirus as a potential etiologic agent has been documented in only two of these cases. In the past, symptomatic treatment of pregnant patients with severe and progressive symptoms has been associated with an unacceptably high rate of maternal morbidity and mortality. Recent studies have shown convincingly that plasmapheresis is the treatment of choice for nonpregnant patients acutely ill with Guillain-Barre syndrome, but data regarding its use in pregnancy are limited. We report three patients, two of whom had positive cytomegalovirus titers, in whom aggressive plasmapheresis prevented the need for ventilatory support and its inherent increase in maternal morbidity and mortality. PMID- 1870801 TI - Treatment of antenatal myasthenia gravis. AB - Maternal myasthenia gravis has been associated with the presence of neonatal myasthenia and sometimes fatal congenital anomalies. As a result, antenatal therapy directed at fetal sequelae may be indicated. We present the case of a pregnant myasthenic woman whose two previous pregnancies had ended in neonatal deaths from fetal deformations that were presumably due to maternal myasthenia. Serial plasmaphereses and oral prednisone therapy were used in an attempt to depress maternal anti-acetylcholine receptor antibody titers. As anti acetylcholine receptor antibody titers fell, fetal breathing movements became apparent by ultrasound, and as these titers rose, no fetal breathing movements were apparent. Our patient delivered an infant with transient neonatal myasthenia but normal pulmonary development and no deformations. We suggest that the therapy given may have improved the outcome of this pregnancy compared with her two previous pregnancies. PMID- 1870802 TI - Idiopathic aldosteronism in pregnancy. AB - This is the first reported case of the idiopathic type of primary aldosteronism in pregnancy. The severely hypertensive patient was unresponsive to treatment with high doses of four antihypertensive agents administered concurrently. A drastic improvement in blood pressure was noted within 24 hours of beginning enalapril maleate, although subsequent deterioration in fetal status led to delivery at 26 weeks' gestation. Alternatives to standard medical therapy may be necessary for this rare but potentially life-threatening disease during pregnancy. PMID- 1870803 TI - Factor XII deficiency and pregnancy. AB - A 19-year-old primigravida with known factor XII deficiency (prepregnant factor XII level of 21%) presented with placental abruption and preterm labor at 26 weeks' gestation. A healthy 925-g female infant was born by spontaneous vaginal delivery. The mother had no postpartum hemorrhage or further complications, and the infant demonstrated no intracranial or other forms of hemorrhage up to 70 days of age. The infant's factor XII level was 34% (normal for her age). There are only two previous reports of factor XII deficiency in pregnancy cited in the English literature, and both were uncomplicated. In view of the risk of thromboembolic complications in nonpregnant individuals with factor XII deficiency, pregnant women with a prolonged activated partial thromboplastin time and no lupus anticoagulant or anticardiolipin antibody syndrome should also be investigated for deficiencies of factors VIII, IX, and XII. These patients should be given the appropriate counseling and should be monitored for features of thromboembolism if factor XII deficiency is confirmed. PMID- 1870804 TI - Gonococcal endocarditis complicating pregnancy: a case report and literature review. AB - The incidence of gonorrhea has decreased substantially in the past decade. Disseminated gonorrhea is more common in women than in men, although gonococcal endocarditis is more common in men. Disseminated gonorrhea is most commonly described in women during menses or pregnancy. Only two cases of gonococcal endocarditis during pregnancy have been reported in the literature since 1942. We report a patient who experienced sudden hemodynamic decompensation at 30 weeks' gestation, resulting in fetal death. Aortic valve replacement was performed, but extensive involvement of the aortic root made complete eradication of infection impossible and eventually resulted in maternal death. PMID- 1870805 TI - Hypercalcemic crisis in pregnancy associated with excessive ingestion of calcium carbonate antacid (milk-alkali syndrome): successful treatment with hemodialysis. AB - Severe hypercalcemia, a potentially life-threatening condition, has been reported rarely during pregnancy. A patient with hypercalcemic crisis associated with excessive ingestion of absorbable calcium antacid was treated successfully with hemodialysis as well as other therapeutic measures, such as saline diuresis. This acute therapy resulted in long-term normalization of maternal calcium levels. The fetus, who exhibited a low biophysical score during the initial admission, was delivered a month later and had an uncomplicated neonatal course. Acute hemodialysis can be an effective, rapid, and safe method of lowering serum calcium levels in pregnant patients with severe hypercalcemia unresponsive to other medical therapies. PMID- 1870806 TI - Acute transient thrombocytopenia associated with cocaine abuse in pregnancy. AB - A case is described of cocaine-induced severe transient thrombocytopenia associated with a hypertensive crisis at 21 weeks' gestation. Liver function tests and coagulation studies were all within normal ranges. Blood pressure was controlled with hydralazine. This clinical presentation, similar to severe preeclampsia, should be considered in the differential diagnosis of acute hypertension and low platelet count, especially in early gestations when preeclampsia is relatively rare. Unlike severe preeclampsia, for which active intervention and delivery are usually selected, cocaine-related hypertension thrombocytopenia, especially in very premature gestations, may warrant conservative management. PMID- 1870807 TI - Cocaine and indomethacin: fetal anuria, neonatal edema, and gastrointestinal bleeding. AB - A case is reported in which exposure to cocaine and indomethacin was associated with development of fetal anuria, anasarca, and neonatal gastrointestinal hemorrhage. Cocaine and indomethacin may act synergistically to adversely affect renal, cardiovascular, and platelet function. It may be prudent to obtain a drug history and urine screen for cocaine before instituting indomethacin therapy for preterm labor or polyhydramnios. PMID- 1870808 TI - Eikenella corrodens chorioamnionitis. AB - Eikenella corrodens was once considered a microorganism of little clinical consequence. But over the past decade, there has been a marked increase in the number of reports of serious infections caused by this organism. We present a case of E corrodens chorioamnionitis in a patient with intact membranes. This is the second known case of its kind to be reported in the medical literature. The true incidence of obstetric and gynecologic infections may be much higher than reported because of the organism's susceptibility to routine antibiotic regimens and the failure of some strains to exhibit characteristic colony morphology on solid agar. PMID- 1870809 TI - Preeclampsia, trisomy 13, and the placental bed. AB - Genetic predisposition and abnormal trophoblastic function are thought to contribute to the development of preeclampsia. A multipara developed severe preeclampsia and subsequently delivered a live growth-retarded infant with trisomy 13. Biopsy of the placental bed taken immediately after delivery demonstrated inadequate trophoblastic remodeling of the maternal uterine vasculature, with an absence of normal physiologic changes in the spiral arteries. This case suggests that fetal trisomy 13 can be associated with preeclampsia in multiparous women and that abnormal trophoblastic invasion may contribute to the pathophysiology. PMID- 1870810 TI - Placenta previa percreta involving the urinary bladder: a report of two cases and review of the literature. AB - The incidences of both placenta previa and placenta accreta are increased in patients with scarred uteri, and patients with uterine scars and placenta previa are at increased risk for also having placenta accreta. Two cases are presented of placenta previa percreta with involvement of the urinary bladder necessitating cesarean hysterectomy, partial cystectomy, and, in one case, bilateral ureteral reimplantation. Both patients had two previous cesarean deliveries. Serious hemorrhage is common in patients with placenta percreta. The primary goal of surgical management must be to control bleeding, which usually requires resection of all tissue involved by the infiltrating placenta. After hemorrhage is controlled, the surgeon must reestablish the integrity of the urinary system and reconstruct the pelvis as necessary. PMID- 1870811 TI - Placenta membranacea with placenta increta: a case report and literature review. AB - The pregnancy of a patient with placenta membranacea associated with placenta increta and a live-born infant is described, and the literature covering placenta membranacea is reviewed. A total of 26 cases of placenta membranacea in the second and third trimesters have been reported. The condition appears to have an incidence of 1:20,000-40,000, and there have been 14 reported live births associated with this rare placental anomaly. Antepartum and postpartum hemorrhage were reported to complicate 83 and 50% of the cases, respectively. Approximately 30% of the cases involved some form of abnormal placental adherence. PMID- 1870812 TI - The sonographic diagnosis of circumvallate placenta. AB - Circumvallate placenta, a form of placenta extrachorialis, should be included in the differential diagnosis of vaginal bleeding in the second trimester with a normally implanted placenta. Heretofore, the diagnosis was made after delivery. This report presents a case of circumvallate placenta diagnosed prenatally by ultrasound. Key features included an infolding of the fetal membrane upon the fetal surface of the placenta during the middle of the second trimester. By the third trimester, only a bright border at the periphery of the placenta was noted. Antenatal diagnosis can be made and pregnancy outcome potentially altered. PMID- 1870814 TI - Massive fetomaternal hemorrhage treated by fetal intravascular transfusion. AB - Two cases of massive fetomaternal hemorrhage are presented. Both women noted a decrease in fetal movement and were advised to come to the hospital for fetal heart rate monitoring. Sinusoidal fetal heart rate patterns were observed and Kleihauer-Betke testing was positive for fetomaternal hemorrhage. The fetuses were preterm and therefore funipuncture was done, which confirmed profound anemia in both. Fetal intravascular transfusion was performed. Shortly after conclusion of the transfusion, prolonged bradycardia occurred in both fetuses and delivery was accomplished by cesarean. Both infants survived. PMID- 1870813 TI - Acute twin-twin transfusion: a possible mechanism for brain-damaged survivors after intrauterine death of a monochorionic twin. AB - Intrauterine death of one twin in monochorionic pregnancies is associated with increased mortality and morbidity for the survivor. This has been attributed to the consequences of intrauterine disseminated intravascular coagulation (DIC) initiated by the dead twin. We describe a case in which the fetal cerebral and renal lesions typically found in survivors occurred without any derangement in coagulation. Instead, acute twin-twin transfusion was suggested by the presence of severe anemia in the surviving fetus at delivery. We suggest that the lesions frequently found in the survivors are often due to acute hemodynamic and ischemic changes resulting from acute twin-twin transfusion at the time of intrauterine death, rather than to late-onset DIC. This hypothesis has an important implication for future management: Intervention must occur before intrauterine death if neurologic sequelae in the survivor are to be prevented. PMID- 1870815 TI - Fetal supraventricular tachycardia and hydrops fetalis: combined intensive, direct, and transplacental therapy. AB - A 25-week fetus with severe hydrops fetalis secondary to supraventricular tachycardia was treated with fetal intramuscular injections of digoxin in conjunction with maternal intravenous digoxin, followed by oral digoxin and subsequently by oral procainamide therapy. Fetal umbilical blood sampling revealed poor placental transfer of digoxin, even after 2 weeks of therapeutic maternal levels. This case suggests that direct fetal therapy is of value in the treatment of some fetuses with supraventricular tachycardia, and lends further evidence that the role of transplacental digoxin therapy is limited in the compromised fetus. It also demonstrates that resolution of hydrops may require a prolonged period. PMID- 1870816 TI - Prenatal diagnosis of fetal left ventricular aneurysm: a case report and review. AB - Fetal echocardiography in a 30-year-old black woman, gravida 4, para 3, demonstrated left ventricular aneurysm. This was confirmed by color flow pulsed Doppler techniques. After delivery, neonatal echocardiography and magnetic resonance imaging further confirmed the diagnosis. The infant was followed closely and underwent surgical correction at 8.5 months of age. Before surgery, cardiac catheterization demonstrated normal hemodynamic function. A review of the literature revealed a paucity of information. Issues of prenatal diagnosis, antenatal surveillance, method of delivery, and neonatal follow-up are not well defined in either the obstetric or pediatric cardiology literature. A rationale for our approach to this complex problem is presented. PMID- 1870817 TI - Transvaginal sonographic follow-up on the formation of fetal cephalocele at 13-19 weeks' gestation. AB - An occipital meningocele was detected by transvaginal sonography in a fetus of 13 weeks' gestation. This changed at 14 weeks to a cephalocele, which disappeared at 15-16 weeks and was detected again at 19 weeks. It is possible that sliding backward and forward of the herniated brain tissue caused this sequence of events. PMID- 1870818 TI - An ectopic pregnancy in the upper retroperitoneum following in vitro fertilization and embryo transfer. AB - Thirty-seven days after successful embryo transfer, a chorionic vesicle was recovered from the upper abdominal retroperitoneal space in a patient presenting with an acute life-threatening hemorrhage. This is the first case report of a retroperitoneal ectopic pregnancy which, although uncommon, is a potentially fatal complication of in vitro fertilization-embryo transfer. PMID- 1870819 TI - Recurrent abortion and the diagnosis of Wilson disease. AB - We describe the first patient with Wilson disease and recurrent abortion who was effectively treated with oral zinc for both conditions. Between the ages of 21 26, this patient experienced seven successive unexplained abortions. At age 27, neurologic signs and liver function disturbances appeared. Wilson disease was diagnosed when Kayser-Fleischer rings were detected in the cornea. Decoppering therapy was instituted with zinc sulfate per os. By the age of 31, hepatic and neurologic signs had vanished. The patient conceived, and after an uncomplicated eighth pregnancy she delivered her first healthy child. Two years later, a ninth pregnancy was equally successful. The chance that Wilson disease may be the cause of recurrent abortion is small. However, because the disease is fatal if left untreated and because it is an underdiagnosed disease, we recommend screening for Wilson disease in cases of unexplained recurrent abortion when family history demonstrates consanguinity or neurologic, psychiatric, and/or liver disorders. A strategy to this end is proposed. PMID- 1870820 TI - Streptococcal toxic shock associated with septic abortion. AB - The group A streptococcus is capable of producing exotoxins that have been linked to a toxic shock-like syndrome. Streptococcal toxic shock is a rapidly progressive disease associated with injury to multiple organ systems and a 30-60% mortality rate. We present a case of a 40-year-old woman who developed group A streptococcal toxic shock following a spontaneous abortion. She required surgical debridement, pulmonary artery catheterization, mechanical ventilation, and massive transfusions. Clinicians must be aware of the presentation of this disease, as its incidence appears to be increasing. PMID- 1870821 TI - Ectopic ureter: a rare cause of purulent vaginal discharge. AB - We report two cases in which urologic anomalies presented with vaginal discharge and fever in young women, aged 9 and 18 years. Both patients were ultimately diagnosed as having duplicated collecting systems with ectopic upper-pole ureters opening into the introitus. Although congenital urologic anomalies are a rare cause of vaginal discharge in young women, they should be included in the differential diagnosis of patients presenting with these symptoms. PMID- 1870822 TI - Suburethral paraganglioma. AB - Masses presenting beneath the urethra are not uncommon. Besides ureteral diverticula, which account for the vast majority of these masses, a multiplicity of heterogeneous benign and malignant tumors have been encountered in this region. To the best of our knowledge, we report the first case of a neuroendocrine tumor, a paraganglioma, discovered in the anatomical compartment between the urethra and vagina. When evaluating a patient with a suburethral mass, it is important to consider paraganglioma as part of the differential diagnosis because unwitting surgical removal of a functional catecholamine secreting tumor may precipitate a severe hypotensive episode and/or death. PMID- 1870823 TI - Unexplained displacement of ipsilateral ovary and fallopian tube. AB - During routine laparoscopy, the right fallopian tube and ovary were noted to be displaced. Ovarian and fallopian tube tissue were found on biopsy of adjacent omentum. The most probable cause is asymptomatic torsion of the right adnexum; therefore, evaluation of the renal system with intravenous pyelogram is probably not necessary. PMID- 1870824 TI - Massive evisceration: a complication following sacrospinous vaginal vault fixation. AB - This report describes a spontaneous vaginal vault prolapse in association with massive evisceration following sacrospinous vaginal vault fixation. Careful attention to surgical technique is critical to the success of the operation. In particular, good apposition of the vaginal vault to the sacrospinous ligament and adequate repair of an enterocele should avoid this complication. PMID- 1870825 TI - Clinical usefulness of serum squamous cell carcinoma antigen for early detection of squamous cell carcinoma arising in mature cystic teratoma of the ovary. AB - Squamous cell carcinoma arising in mature cystic teratoma of the ovary is rarely diagnosed preoperatively. We measured the pre-treatment serum levels of squamous cell carcinoma antigen in three stage I patients in order to evaluate its usefulness as a tumor marker for early detection of the disease. The serum levels were elevated in each case, to 26.9, 5.1, and 3.2 ng/mL, respectively, and rapidly dropped to within the normal range after treatment. All patients are recovered and show no evidence of recurrence, and the levels of serum squamous cell carcinoma antigen have remained within normal limits. These results suggest that measurement of the serum squamous cell carcinoma antigen level may be useful in diagnosing an early-stage primary squamous cell carcinoma arising in a mature cystic teratoma of the ovary. An elevated preoperative serum level of squamous cell carcinoma antigen may indicate the need for a rapid pathologic examination of the tumor to look for malignant elements and may influence the surgical regimen. PMID- 1870826 TI - The concept of uterine preservation with ovarian malignancies. AB - A 30-year-old woman with bilateral, recurrent, borderline papillary serous cystadenocarcinoma of the ovary was treated with bilateral oophorocystectomy and omentectomy with uterine preservation. Ten years later, through induction of an artificial endometrial cycle and ovum donation, she conceived twins and delivered two healthy infants. Staging exploratory laparotomy at the time of cesarean delivery was negative for malignancy. This case illustrates the value of uterine preservation for cases in which classical teaching has indicated hysterectomy with bilateral salpingoophorectomy. PMID- 1870827 TI - Adrenal carcinoma presenting with postmenopausal vaginal bleeding. AB - A 63-year-old woman presented with a 3-day history of vaginal bleeding. Pelvic examination and ultrasound revealed bilateral atrophy of the ovaries and a uterus of 8.8 x 3.3 x 4.0 cm. Serum estradiol (E2) was 300 pg/mL. Cushing syndrome was diagnosed biochemically, and computed tomography of the abdomen revealed a 5-cm left adrenal mass and tumors in the liver and lung. A pathologic diagnosis of metastatic adrenal carcinoma was made after surgery. This case demonstrates that adrenal carcinoma can produce high E2 levels in a postmenopausal woman, leading to uterine enlargement and vaginal bleeding. Adrenal carcinoma should therefore be included in the differential diagnosis of postmenopausal vaginal bleeding. PMID- 1870828 TI - Cecal rupture after continent ileocecal urinary diversion during total pelvic exenteration. AB - Continent ureteral diversion at the time of pelvic exenteration avoids an external appliance and allows patients to retain "bladder" reservoir function. The technical difficulty of this procedure requires meticulous attention to operative and perioperative care, particularly after pelvic irradiation. A patient with recurrent stage IIIB carcinoma of the cervix underwent total pelvic exenteration with reconstructive procedures including low rectal anastomosis, neovagina formation, and ileocecal (Indiana) continent diversion. Early catheterization of the reservoir began 2 weeks postoperatively. One week later cecal rupture occurred, not related to suture line (technical) failure. Because of the high wall tension and reduced compliance in the irradiated cecum, we do not recommend catheterization of the urinary reservoir before 4-6 weeks. In order for continent diversion to become the standard diversion in exenteration patients, the major complication rate must remain comparable to that of noncontinent diversion. PMID- 1870829 TI - Ohio's new living will legislation. PMID- 1870830 TI - Is durable power working in Ohio? PMID- 1870831 TI - Legal dilemmas ahead for HIV-infected physician. PMID- 1870832 TI - Cincy researchers study Chernobyl victims. PMID- 1870833 TI - A biopsychosocial profile of the geriatric population who frequently visit the emergency department. AB - Over the last two decades the emergency department has become the primary source of health care for a large segment of the population. While this practice is discouraged by ED staff and primary care providers, it is an unfortunate reality. Recent literature has examined the use of the ED from many different angles. Areas investigated include various demographics (age, sex, race, etc.), method of payment, presenting complaint, and availability of primary care. Repeated inappropriate use of ED services by individuals (the so called "frequent fliers") has also attracted attention. The interest in this sub-population of patients is presumably due to the prevalence as well as the excessive costs of this behavior. In the present study a retrospective chart review was used to establish the biopsychosocial profiles of geriatric patients identified as being frequently seen in the emergency department for non-urgent conditions. Even though only 11% of the US population is age 65 or older, the elderly in America consume 30% of the health care resources, and in the next 20 years that figure is expected to climb to 50% (1). Demographics, ED presentation, diagnosis, and treatment as well as past medical history were collected. The objectives of the study were to identify these elderly frequent fliers and determine what could be the reasons behind the inappropriate use of emergency department resources by these patients. The average age of the sample was 74. The marital status of the sample was as follows: 42.4% widowed, 27.2% married, 15% divorced, and 18.5% single. Over half (52.6%) of those patients were brought to the ED by ambulance. The most common presenting complaint was chest pain (20.8%), followed by somatic complaints (18.9%), GI (16.1%), dyspnea (13.7%), and change in mental status (12.8%). The most prevalent ED diagnosis was psychiatric (18.4%) in nature. The other diagnoses were somatic (16.6%), GI (11.8%), and pulmonary (10.9%). 88.5% of the sample reported to have a primary care physician. However, 45% of the ED visits occurred between 9 AM and 5 PM at a time when a physician should have been available. The admission rate for this sample was 21.9%, which is half what has been found in the "normal" elderly, as reported by McDonald and Abrahams. PMID- 1870834 TI - Ultrastructural investigation demonstrating reduced cell adhesion on heparin surface-modified intraocular lenses. AB - A major attention is focused at present to the surface characteristics of intraocular lenses (IOLs), which determine the biological response to the prostheses. There is now an overwhelming information on the fact that some cell types adhere to a lesser extent onto heparin-surface-modified (HSM) polymethylmethacrylate (PMMA) IOLs, either in vitro and in vivo. The present work aimed at sheding new insights by applying ultrastructural techniques of analysis. Our results basically confirm that human fibroblasts, platelets and monocytes are less in number when cultured onto HSM PMMA IOLs as compared to untreated PMMA IOLs. In addition: (1) the submicroscopic morphology of the cells cultured onto HSM PMMA IOLs appears to be normal, thus confirming the noncytotoxicity of the material; (2) fibroblasts grown onto PMMA IOLs are confluent and multilayered; they appear to be in a state of intense activity; the cytoskeletal elements are regularly arranged, and several points of contact at the interface are found; the rare cells present on HSM IOLs do not show at all any of these features; (3) the basic forms of resting and activated platelets are seen onto PMMA IOLs while no sign of activation is observed onto HSM IOLs, and (4) the ultrastructural morphology of monocytes does not differ significantly between the different IOLs. However, other studies are still in progress in order to localize and quantitate the specific receptors responsible for the eventual activation of these cells. PMID- 1870835 TI - Doxium (calcium dobesilate) reduces blood hyperviscosity and lowers elevated intraocular pressure in patients with diabetic retinopathy and glaucoma. AB - In a double-blind randomized clinical trial, 79 non-insulin-dependent diabetic subjects with early retinopathy and open-angle glaucoma received orally either three 500-mg capsules of Doxium (calcium dobesilate) daily for 6 months (41 patients) or three placebo capsules daily for the same period (38 patients). At the end of the study statistically significant differences in the Doxium group compared with the placebo group were recorded: intraocular pressure, visual field defects, surface area of retinal hemorrhages, and whole blood and plasma viscosity were reduced (p less than 0.001). Coefficient of outflow facility and serum albumin concentration were increased (p less than 0.001 and p less than 0.02, respectively). These results suggest that increased whole blood viscosity is a risk factor for diabetic retinopathy and for glaucomatous optic nerve damage. They further suggest that Doxium reduces blood hyperviscosity and lowers intraocular pressure, with a beneficial effect on retinal state and visual fields. PMID- 1870836 TI - Incidence of posttrabeculectomy cataract among Arabs in Kuwait. AB - Trabeculectomy was performed in 466 glaucomatous eyes of 342 patients. Of these eyes, 54% appeared to have lens opacities. However, 35% of these cases had the cataract preoperatively and in 19% the cataractous changes appeared to develop postoperatively. The risk of development of posttrabeculectomy cataract seemed to increase with patient age. In addition, our results show that 51% of the patients developing a postoperative cataract had hypotony with a flat anterior chamber, 24.4% had hyphema and 20% had uveitis. Our findings suggest that the main risk factors involved in the posttrabeculectomy development of cataract are age, hypotony, hyphema, uveitis and probably minor trauma to the lens by continuous circulation of the aqueous humor through the surgical fistula. PMID- 1870837 TI - Histological differentiation in fetal organ-cultured and human cataractous eye lenses. AB - Swine fetal organ-cultured lenses were studied histoautoradiographically and histologically, and human cataractous lenses were examined histologically to investigate the continuous differentiation of epithelial cells into fiber cells in the lens equatorial region. Both lens groups studied presented abnormal differentiation: the equatorial epithelium proliferates; nucleus-containing cortical fibers turn into bladder cells (of Wedl), and the formation of new cortical fibers stops. PMID- 1870838 TI - Zinc in tears. AB - The tear and serum zinc (Zn) levels were determined simultaneously by atomic absorption spectrophotometry in 11 healthy subjects. The mean tear Zn level was found to be 1.537 +/- 0.146 (SEM) ppm while the mean serum Zn level was found to be 1.03 +/- 0.046 (SEM) ppm. PMID- 1870839 TI - Microradiographical determination of the dry mass density in the rat retina. AB - A method for the quantitative measurement of the dry mass density in retinal tissue is presented. Cryosections of rat retinas were freeze-dried and exposed to soft X-rays together with a reference system. The section thickness was measured optically. The X-ray energy absorbed by the retinal tissue was recorded photographically and the microradiographs were evaluated photometrically. These measurements were used to estimate the dry mass density for each retinal layer. Sources of variation were evaluated. The precision was found adequate. The present method allows a localized determination of the dry mass density and of the hydration in the retina at a microscopic resolution. PMID- 1870840 TI - Polymorphonuclear leukocytes and bacterial growth of the normal and mildly inflamed conjunctiva. AB - We examined 304 conjunctiva in 152 subjects by clinical, cytologic, and bacteriologic methods. Bacteriologic samples were evaluated after a 48-hour incubation. Bacterial growth was found in 8 (20.5%) of 39 patients with clinically normal conjunctiva and no polymorphonuclear leukocytes (PMNs), and in 8 (61.5%) of 13 subjects with clinically normal conjunctiva and evidence of PMNs. Bacterial growth also was observed in 4 (40.0%) of 10 patients with clinically mild conjunctivitis and no PMNs, in 10 (24.4%) of 41 patients with clinically mild conjunctivitis and a mixture of inflammatory cells or predominantly lymphocytes, and in 37 (75.5%) of 49 patients with clinically mild conjunctivitis and evidence of PMNs. The presence of PMNs was well correlated with the existence of rapid-growing bacteria. PMID- 1870841 TI - Selenium concentration in ocular tissues and fluids. AB - A simple, precise method for the analysis of selenium (Se) in ocular fluids and tissues using electrothermal atomic absorption spectroscopy is presented. Se concentrations ranged from 0.23 to 0.41 microgram/g wet weight in the cornea, iris, lens, and retina. The Se concentration in aqueous humor was 0.008 microgram/ml, thus much lower than that of plasma (0.21 microgram/ml). The concentration of protein in aqueous humor is about 1.0% of plasma. Since in plasma, Se is entirely bound to proteins, it is likely that the difference in Se concentration between plasma and aqueous humor reflects the relative distribution of protein between these fluids. PMID- 1870842 TI - Anticataractogenic property of gamma-glutamylcysteine ethyl ester in an animal model of cataract. AB - The anticataractogenic potential of gamma-glutamylcysteine ethyl ester was investigated in model cataracts induced by L-buthionine sulfoximine. Subcutaneous injection of the ester (0.625-2.5 mmol/kg) effectively inhibited cataractogenesis in suckling mice. Treatment of mice with L-buthionine sulfoximine alone resulted in a marked reduction of the glutathione content in the eyes. This deprivation of glutathione was mitigated, to a significant degree, by coadministering gamma glutamylcysteine ethyl ester. In an experiment with rat lens in culture, gamma glutamylcysteine ethyl ester was found to elevate the lenticular level of glutathione. These results indicate that gamma-glutamylcysteine ethyl ester is able to permeate across biomembranes and serves as an excellent precursor for glutathione biosynthesis, thereby exerting its anticataractogenic activity. PMID- 1870843 TI - Racial variation of optic disc size. AB - The optic disc size was measured in 125 volunteers without ocular disease. The horizontal disc diameter and the disc area were significantly smaller in whites and Hispanics than in non-American Indians, Orientals and blacks, and smaller in females than in males. There was no correlation between disc size and age. Future studies analyzing optic disc morphometry need to account for the influence of sex and race. PMID- 1870844 TI - Histochemical analysis of experimental granulomatous uveitis. AB - We have previously demonstrated the effects of various inhibitors of arachidonic acid metabolism on experimental lens-induced granulomatous uveitis. In the present study, we investigated the effect of these same inhibitors on the expression of lysosomal enzymes at different stages of choroidal inflammation in experimental lens-induced granulomatous uveitis and compared this to the inflammation observed at each stage examined. Lysosomal enzymes such as acid phosphatase, beta-glucuronidase and succinate dehydrogenase are known to be liberated during the maturation of mononuclear phagocytes to epithelioid cell granulomas. Although animals treated with nordihydroguaiaretic acid showed less severe inflammation than did indomethacin-treated or control animals, none of these agents appeared to affect the expression of acid phosphatase and beta glucuronidase, as determined histochemically. Succinate dehydrogenase could not be detected in any of the eyes examined, even though sections of liver and kidney from these same animals were positive for this enzyme. PMID- 1870845 TI - Nosocomial infections of ocular conjunctiva in newborns delivered by cesarian section. AB - Colonization of the ocular conjunctiva in newborns delivered by cesarian section occurs usually within the first day of life. We have studied the flora of the ocular conjunctiva at birth, from 19 newborns delivered by cesarian section, coming from two different maternity hospitals. Ocular conjunctiva cultures yielded the main predominant flora in both maternity hospitals considered. The most common genus of this flora are: Staphylococcus, Corynebacterium and Propionibacterium acnes. Peptostreptococcus productus, Neisseria, Eubacterium and Clostridium perfringens are isolated occasionally. In newborns delivered by cesarian section, this flora principally acquired may be the consequence of the presence of bacteria in the ambient air, as well as differences in care provided by the nosocomial personnel. PMID- 1870846 TI - Comparison of phosphate metabolites of the ocular humors. AB - Ocular humors (aqueous humor and vitreous body) were obtained from porcine eyes. Perchloric acid extracts were prepared from aqueous and vitreous aspirates, and phosphorus-31 nuclear magnetic resonance spectroscopy 31P-NMR performed. Resonance signals from four high-energy phosphate groups (phosphocreatine, adenosine tri- and diphosphate and the dinucleotides) and nine low-energy phosphate groups [dihydroxyacetone phosphate, hexose-6-phosphate, alpha glycerophosphate, fructose-1,6-diphosphate, ethanolamine phosphate, choline phosphate, inorganic orthophosphate (Pi), glycerol-3-phosphorylethanolamine and glycerol-3-phosphorylcholine] were present in the aqueous humor and/or vitreous body. Vitreous body phosphates significantly elevated relative to that of the aqueous humor were: DHAP, Hex 6-P, alpha-GP, Fru 1,6-diP, CP, GPE, PCr, ATP, ADP, and the dinucleotides; only Pi was significantly lower. Six metabolic indices (monoesters, diesters, monoesters/diesters, monoesters/Pi, ATP/Pi, energy modulus) were determined; all vitreous body indices were significantly higher than those of the aqueous humor. In particular, the energy modulus, a measure of overall metabolic energy status, was higher in the vitreous body (0.121 +/- 0.047) than in the aqueous humor (0.05 +/- 0.021). PMID- 1870847 TI - Endothelial cells of rabbit cornea in different storage conditions. A quantitative cytochemical study. AB - The metabolic functions of endothelial cells of the rabbit cornea in different storage conditions were studied using quantitative cytochemistry. The corneas were stored for 2 h, and 1, 3, 7, 14 and 21 days in dexol at 4 degrees C and in culture medium at 37 degrees C. It was shown that glycolysis as expressed by the activity of the cytosolic enzymes glyceraldehyde 3-phosphate dehydrogenase, glucose-6-phosphate dehydrogenase and lactic dehydrogenase is well preserved for 1 week in dexol and for 3 days only in the culture medium. Mitochondrial enzymes as shown by succinate dehydrogenase and fatty acid oxidation activity show a similar pattern. Uridine diphosphoglucose dehydrogenase, which plays an important part in proteoglycan synthesis, is markedly decreased in both media, but retains its activity in dexol for a slightly longer time. Keratan and chondroitin sulfate content show a sharp drop in the culture medium at 37 degrees C as compared to dexol. This study demonstrates the superiority of dexol at 4 degrees C over the culture medium at 37 degrees C. Quantitative cytochemistry is a useful tool for studying the metabolism of endothelial cells. PMID- 1870848 TI - [Fatigue of the respiratory muscle and respiratory insufficiency]. AB - Recent results on respiratory muscle function are reviewed, with special regard to the muscle fatigue theory of respiratory failure. In this respect diagnostic measures and clinical symptoms are reported. Therapy is directed to reduce the work of respiratory muscles and temporarily rest them. Within this special role is given to the treatment with respirator and positive pressure breathing. PMID- 1870849 TI - [Follow up of extremely low birth weight infants at the age of 8-11 years (late prognosis of perinatal factors)]. AB - Thirty-four long-term survivors of a five-year period (1977-1981) weighing 1000 g or less at birth were followed-up at 8-11 years of age. Fifty per cent of this population was qualified as normal. The great majority of the children (24) attended normal school but 7 (20.6%) with need of special help. There were only three children (8.8%) with severe functional impairment. The rate of survival was 30% at the Neonatal Intensive Care Unit of the Department of Pediatrics, University Medical School, Debrecen at that period of time. The authors analyze in detail the connections of the perinatal events and the outcome. While survival was influenced primarily by hemorrhagic complications beyond immaturity, the long term prognosis depended on birth asphyxia, recurrent apneic spells and requirements for oxygen therapy. PMID- 1870850 TI - [Localization of primary and recurrent bladder tumors]. AB - The location distribution of the primary and recurrent bladder tumours was studied in 417 patients. The authors decided that the ureteral orifices, the lateral walls are the most common places of primary superficial bladder tumours. The favoured places of the primary invasive bladder tumours are the posterior walls. They found not so much disparity between the site of primary and recurrent invasive bladder tumours, but the difference between the site of the primary and recurrent superficial bladder tumours is remarkable. They decided, according to their patients material, that the recurrent superficial bladder tumours take places more frequently on the posterior walls, the dome and the anterior walls. The explanation of this phenomenon may be the tumour cells implantation during the TUR. The authors survived all the other processes can yield the local and distant recurrent bladder tumours and understanding of this processes can result in a better understanding of the location distribution of the recurrent bladder tumours on the one hand and it can help us to avoid or decrease the recurrences on the other hand. PMID- 1870851 TI - [Ultrasonic diagnosis of pathological changes of the knee]. AB - 54 knee joints clinically suspicious of presenting a lesion were examined. The ultrasound examination proved to be of great value in disclosing both anatomical details and lesions. Our results closely correlate with the abnormalities found at operation. We agree with literature that ultrasound method is adequate for diagnosing abnormalities in the knee. This method has been recommended as first choice for in many cases it fields a final diagnosis. PMID- 1870852 TI - [Persistent trigeminal artery associated with pituitary adenoma]. AB - The authors report of a case with a pituitary macroadenoma which was associated with a persistent trigeminal artery. The tumour was removed by transsphenoidal microsurgical approach to the sella turcica. To recognise the developmental anomaly is very important to avoid complications during operation. PMID- 1870853 TI - [Centenary of the birth of Endre Jeney]. PMID- 1870854 TI - [Sarcastic remarks about the current practice of medical consultation --or: why do I dislike to participate in consultations?]. PMID- 1870855 TI - [Speculations about the compulsory regional on duty service of pediatricians]. PMID- 1870856 TI - [Diagnostic value of alkaline phosphatase isoenzymes]. AB - Among the serum enzymes used for diagnostic purposes the alkaline phosphatase (AP) is one of the oldest and the most frequently applied laboratory tests. Increased activity found in the serum is a consequence of certain hepato-biliary disorders, different bone diseases, endocrine syndromes, kidney illnesses and malignant tumors as well. From the study of the pattern of the isoenzymes of the serum-AP information of practical importance may be gained by which many differential-diagnostic problems can be solved. For the clinical-chemical laboratories methods that use electrophoretic separation on different membranes or gels are recommended. Patterns characteristic for different diseases may well be differentiated from normal constellation. AP-isoenzymes help to reveal cholestases at early stages, some disorders of bone metabolism and malignant processes as well. PMID- 1870857 TI - [Transabdominal chorion aspiration in the second pregnancy trimester]. AB - The authors report their experiences with 377 transabdominal chorionic villi samplings performed in the second trimester of pregnancy, between 1987-1989. They used the double needle technique with continuous ultrasound guidance. In every case they could get a sufficient amount of villi from one puncture, and there was no unsuccessful direct chromosome-preparation. The obstetrical complications of the procedure were measured by the analysis of the outcome of the first 300 pregnancies intended to continue: the abortion rate after the transabdominal chorionic villi sampling seems to be lower, than after amniocentesis. PMID- 1870858 TI - [Ambulatory cryotherapy of anal fissures]. AB - The author reports 55 patients suffering anal fissure treated by cryosurgery. The method is simple, causes almost no complication, and a real outpatient way of treatment. 47 patients were controlled (85.5 per cent of all). There was no recurrence or remaining complaint. Regarding his own experience the method is recommended. PMID- 1870859 TI - [Cancer of the skin tube--late complication of the ante-thoracic substitution for the esophagus]. AB - The authors report on two patients suffering from benign oesophageal stricture reconstructed by a skin tube. In both skin tube there are developed a malignancy which infiltrated the skin of the chest wall. During one session they performed the removal of the skin tube and the antethoracic reconstruction with ileocolon. The large defect on the thorax was covered in both cases with a latissimus dorsi myocutaneous flap. This provided satisfactory functional and cosmetic result. They point out the effectiveness of the cytostatic combination they administered. Attention should be drawn to the use of the myocutaneous flaps and the regular checking of patients with skin tubes. PMID- 1870861 TI - [Life-work of David Gruby and his role in dermatology]. PMID- 1870860 TI - [Szechenyi and Kossuth on "apparent death"--discussed in Kelet Nepe (People of the East) 150 years ago]. PMID- 1870862 TI - [Distribution of apolipoprotein A I and B in the blood according to age and gender, as well as their relation to blood cholesterol levels in the Hungarian blood donor population]. AB - In this study we assessed the plasma CHOL, HDL cholesterol (HDL-C), apoprotein A I, apoprotein B levels and the polymorphic isoforms of apoprotein A I in Hungarian blood donors (n = 202, average age: 37.5 year). The mean values are presented for age and sex groups, and the data are compared to the international measurements. The mean CHOL concentration was 5.7 +/- 1.1 mmol/l. The CHOL level correlated with age and no significant association was observed with sex. The level of HDL-C showed no correlation with the age and--in opposite to the international data--there were no significant sex differences (women: 1.42 +/- 0.45, men: 1.34 +/- 0.44 mmol/l), which may be explained by the relative high HDL C concentration of Hungarian men. Both apo A I and apo B showed an increase with advancing age. The only difference between the sexes was found in apoprotein A I levels, i. e. it was higher in women than in men (women: 156.3 +/- 23.6, men: 143.8 +/- 26.8 mg/dl). In contrary with the results from other countries, the apoprotein B concentrations in men did not differ from that measured in women (women: 72.1 +/- 17.4, men: 69 +/- 15.8 mg/dl). In relation to the age, in the fifth decade the CHOL, the HDL-C and the apo B levels were higher in women than in men.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1870863 TI - [Changes in interleukin-2 receptor levels in active and inactive pulmonary sarcoidosis]. AB - Current concepts of the immunopathology of sarcoidosis claim a central role for activated pulmonary T-lymphocytes in the maintenance of inflammatory processes. We hypothesized that the pulmonary sarcoidosis disease activity could be monitored by the measurement of serum levels of sIL-2R. We evaluated the sIL-2R in 28 sarcoidosis patients at multiple time points before, during and after therapy and compared the results with the clinical activity of the disease. Before therapy out of 24 episodes with active disease 20 exhibited elevated levels of sIL-2R. Six out of 21 episodes with inactive disease after tappering off corticoid therapy had sIL-2R levels above the upper limit of the normal range. Disease activity under therapy as well segregated with the sIL-2R serum level. Our results demonstrate that the activity of pulmonary sarcoidosis is reflected accurately by the serum level of sIL-2R suggesting that phenomenons of T-cell activation determining the course of the disease are monitored by this approach. PMID- 1870864 TI - [Analysis of radiographic changes in the cervical spine in rheumatoid arthritis]. AB - At the outpatient department of rheumatology 100 patients having definitive or classic rheumatoid arthritis (RA) were examined and their cervical spine was radiographed with traditional X-ray technique. Correlation between roentgen signs and some parameters of the patient and of the disease was processed by regression analysis. The presence of the rheumatoid factor and second line drug therapy did not influence radiographic changes. Degenerative roentgen signs showed a linear correlation with the RA functional capacity and the duration of cervical complaints, and an exponential correlation with the duration of disease and the age of the patient. There was a linear correlation between osteoporosis and all the parameters examined. Inflammatory radiographic changes showed an exponential correlation with functional capacity and duration of cervical complaints, and a linear correlation with the duration of illness and the age of the patient. Symptoms of patients never treated with steroids was more severe than of those receiving short steroid therapy, but less serious than of those who had taken steroids for a long time (for longer than 10 years). PMID- 1870865 TI - [Prognostic value of the study of the blood flow in the fetal median cerebral artery]. AB - Medial cerebral artery blood flow velocity waveforms were examined by pulsed Doppler ultrasound between the 28th and 41st week of pregnancy. It has been found that the vessel showed an increased resistance at the beginning of the third trimester, which significantly decreased till term. In intrauterin hypoxia the diastolic component of the blood flow velocity waveform of medial cerebral artery becomes stronger, marking the centralisation of the circulation. By their opinion the examination of the blood flow in the medial cerebral artery would be an effective additional possibility of the other intrauterine diagnostic methods (both the positive and the negative predictive value were higher than 90%) for the notifying the post-partal condition of the fetus. PMID- 1870866 TI - [A case of inflammatory fibroid polyp of unusual localization]. AB - The case of an inflammatory fibroid polyp of infrequent localization is presented. Altogether 100 cases are reported by summarizing publications in the literature and only a small part of them showed duodenal localization. The patient whose case is presented was subjected to internal examination and later to operation because of acute spastic abdominal pain and loss of weight. Following the description of the case the authors analyse the etiology of this rare disease and the problems of terminology. Radical, curative operation is considered expedient in these cases. The presented case can be regarded as a special one both from the viewpoint of diagnostics and of its duodenal localization. PMID- 1870867 TI - [Comment on the article: Plastic Repair of Umbilical Hernia in Cirrhotic Patients by Valve Implant]. PMID- 1870868 TI - [The use of aminoglycoside antibiotics in pediatrics. (Addendum to a methodologic letter)]. PMID- 1870869 TI - Otitis media: the pathogenesis approach. Definitions and terminology. PMID- 1870870 TI - Otitis media: the pathogenesis approach. PMID- 1870871 TI - The concept of silent otitis media. Its importance and implications. AB - This article defines silent otitis media and describes its continuum of signs and symptoms and its sequelae. Chronic silent otitis media and silent otitis media in children are also examined, and treatment principles are provided. PMID- 1870872 TI - Epidemiology of otitis media. AB - Although otitis media (OM) incidence and prevalence estimates from around the world vary widely, it is clear that OM is a very common childhood disease. It is especially prevalent in children younger than 2 years of age. Furthermore, the earlier the first episode of OM, the greater the risk of subsequent recurrent OM and chronic otitis media with effusion. In addition, a number of other host, agent, and environmental factors have been associated with increased risk of otitis media. Environmental factors that favor the transmission of upper respiratory pathogens increase the risk of OM, recurrent OM, and chronic OME with effusion. Several factors suggest a genetic role in OM susceptibility, which needs further exploration. PMID- 1870873 TI - The concept of pronicity in otitis media. PMID- 1870874 TI - Update on functional anatomy and pathology of human eustachian tube related to otitis media with effusion. AB - New anatomic and histopathologic information regarding the eustachian tube and its surrounding structure as well as possible mechanisms of opening and closing function and dysfunction are discussed in this article. In the past two decades, much light has been shed on the relationship between anomalies of the eustachian tube and the pathogenesis of otitis media with effusion. Now that a technique for obtaining specimens for any histopathologic study that includes the temporal bone as well as the eustachian tube is available, it is hoped that, by harvesting and examining a large number of such specimens, more information will be gained about the relation between eustachian tube pathology and eustachian tube dysfunction, particularly as it relates to otitis media effusion. Only in this way can the clinical management of otitis media be improved. PMID- 1870875 TI - The significance of experimental animal studies in otitis media. AB - Animal models have been instrumental in investigating otitis media. Experimental models have allowed for focused research on how such factors as eustachian tube dysfunction and microbial infection contribute to the pathogenesis of otitis media. Antibacterial therapy and immunologic prophylaxis have been developed using these models. Current research is aimed at generating an objective index of middle ear inflammation for guiding patient management. PMID- 1870876 TI - Mechanisms of otitis media development. Involvement of neurogenic inflammation. AB - The mucosal lining of the middle ear cavity, in particular that of the tympanic membrane and its pars flaccida, exhibits a number of sensory nerves containing the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP). The mucosa is not only rich in nerves and blood vessels but also contains numerous mast cells. It is possible that interactions between histamine containing mast cells and SP-containing and CGRP-containing nerves--neurogenic inflammation--is one of the mechanisms involved in vessel permeability changes in otitis media with effusion. PMID- 1870877 TI - Middle ear inflammatory mediators and cochlear function. AB - Sensorineural hearing loss (SNHL) has been documented in patients with otitis media. Despite a number of clinical and pathologic works dealing with this common problem, animal studies searching for possible relationships between the middle ear inflammation and cochlear function remain insufficient. Bacterial inoculation and ototoxins and inflammatory products in the middle ear cavity cause SNHL in rodents. Human serum albumin placed in the middle ear cavity in chinchillas also produces SNHL, owing to the effects of nonspecific inflammation in the middle ear cavity. Most of the middle ear inflammatory mediators enter the inner ear through the round window route, and alteration of the permeability of the round window membrane plays an important role in causing cochlear dysfunction. Although an immunologic response in the middle ear plays an important role in otitis media, the immunologic response in the inner ear as it relates to middle ear inflammatory mediators requires further study. PMID- 1870878 TI - Immunologic reactivity in the middle ear in otitis media with effusion. AB - This article reviews the immunologic reactivity in the middle ear in both the human disease and in animal models of otitis media. It differentiates the role of immune complexes in otitis media in the animal model and in the human form of middle ear inflammation. The effect of immunization of the gut on the mucosal immune system in the middle ear is briefly explored, and the source of lymphocytes that make their way into the middle ear mucosa from other parts of the mucosal immune system and systemic immune system are briefly discussed. Finally, work from the author's laboratory on the immune response of children with recurrent otitis media due to nontypable Haemophilus influenzae is summarized. PMID- 1870879 TI - Clinical and pharmacokinetic basis for the antimicrobial treatment of acute otitis media. AB - Given the astonishing frequency in childhood of acute otitis media and its significant morbidity, such as hearing loss and possibly speech delay, improving treatment of response is essential. Since bacteria are an important cause of otitis media, antimicrobial treatment remains the cornerstone of such treatment. Over the last four decades, many clinical studies have shown that antibiotics can relieve symptoms and prevalent complications, although a universal cure is still elusive. This article summarizes the most pertinent clinical and experimental research on treating and preventing acute otitis media, with a focus on intervention trials and the pharmacokinetic behavior of antimicrobial drugs. PMID- 1870880 TI - Audiologic evaluation of the otitis media patient. AB - Because of the complexity and variability in the expression of otitis media, its effects on auditory function are diverse. The various influences of otitis media on auditory function are described within this article, including acoustic reflex, audiometry, and tympanometry. PMID- 1870881 TI - Clinical approach to treatment of otitis media. AB - The author presents his experience of 10 years of practice with the treatment of otitis media. He expresses concern for the inconsistencies between articles written recommending treatment protocols for otitis media and actual clinical results from using those treatment protocols. Otitis media varies in its appearance from patient to patient, with its association to other continuous structures and other organ systems making it a challenging disease to correct and cure. Treatment must be tailor-made to fit the patient, and the physician needs to consider other professional opinions and emphasize follow-up care. PMID- 1870882 TI - Pediatric approach to the diagnosis and management of otitis media. AB - The diagnosis of otitis media is complicated by confusing terminology and a disease continuum with overlap between clinical entities. The patient's history often reveals determinants of otitis media chronicity and recurrence. Certain laboratory tests, including tympanocentesis for middle ear fluid culture, may be useful in treatment decisions. Although seven antimicrobial drugs are useful in treating acute otitis media, certain drugs are more useful in specific cases. There are several medical treatment options for chronic otitis media with effusion and for preventing recurrent acute otitis media. PMID- 1870883 TI - Otolaryngologic approach to the diagnosis and management of otitis media. AB - Otitis media is a common childhood disease caused by multiple factors. Understanding the pathogenesis of otitis media is important in the diagnosis and management of it. The mode of therapy should be chosen depending on the type and stage of the disease. Treatment options available to an otolaryngologist include antibiotics, tympanocentesis, myringotomy and tympanostomy tube insertions, adenoidectomy with or without tonsillectomy, exploratory tympanotomy, atympanoplasty, and mastoidectomy. PMID- 1870884 TI - Otitis media: the pathogenesis approach. Assessment and treatment of associated upper respiratory tract pathology. AB - The communication of the middle ear with the nasopharynx via the Eustachian tube makes it susceptible to disease processes of the upper airway. It is therefore necessary for patients with otitis media to have a thorough evaluation of the upper airway for detection and management of any concurrent pathologic condition. This article reviews the various upper respiratory tract pathologic entities associated with otitis media. PMID- 1870885 TI - Otitis media: the pathogenesis approach. General surgical approach based on pathogenesis. An overall approach. AB - The authors present an overall approach and fundamental concepts based on pathogenesis. They advocate an open-minded approach, tailoring the treatment to each individual patient rather than fitting patients into preestablished classifications. PMID- 1870886 TI - Otitis media. 16 years of pathogenesis approach. AB - The authors describe 16 years of their approach to research in otitis media, their rationale, and the concepts that have evolved from their experiments and clinical work. The authors suggest that interest is the key to progress and not laboratory facilities. They extend an invitation to individuals with different backgrounds but common interest in otitis media to work together from the standpoint of pathogenesis. PMID- 1870887 TI - Review article: post-spinal cord injury syringomyelia. PMID- 1870888 TI - Intermittent urethral self-catheterisation: long term results (bacteriological evolution, continence, acceptance, complications). AB - Forty six (9%) out of 520 patients from the years 1976 to 1982 who used intermittent urethral self-catheterisation (IUSC) as the method of bladder drainage at the moment of discharge from the Swiss Paraplegic Centre of Basel were analysed during their rehabilitation period, on discharge, 3, 6 months later and again 5 years later regarding bacteriological changes and urinary tract infections, behaviour of some problem germs such as Proteus, Klebsiella and Pseudomonas, sterile versus clean catheterisation, catheterisation frequency, complications, continence and acceptance of this method. Only 22 patients continue IUSC, 5 have died, 6 use indwelling catheters and 13 are voiding their neurogenic bladder with other methods. Average time on IUSC was 6.6 years (0.5-13 years) in the women's group and 4.6 years (0.5-12 years) in the men's group. Of the remaining 22 patients on IUSC, 23% have sterile urines, 36.5% are infected with E. coli and Enterococci, 4.5% with Staphylococci and the remaining 36% still show the problem germs Pseudomonas (4.5%), Proteus (13.5%) and Klebsiella (18%), but there was a reduction from 19 cases with problem germs in 1983 to 11 cases in 1988. In 1988 5% women and 4% men changed from sterile to clean IUSC (2 out of 11 men using the same catheter for at least 1 week and 2 out of 10 women). The complication rate was astonishingly low during IUSC: being only 4.3% (2 male patients, one with stricture of the urethra and epididymitis, one with autonomous dysreflexia with bladder overdistension). No anti-cholinergic or alpha stimulating agents were used nor continuous antibiotic-prophylaxis and only in one female patient was a bladder denervation procedure performed. No deterioration of the upper urinary tract was observed. The degree of continence remained stable throughout the follow-up, and the same applies to the acceptance of IUSC. The authors conclude that IUSC can be of great help in neuropathic bladder rehabilitation provided that the patients are properly selected, motivated and well instructed and followed throughout the years. PMID- 1870889 TI - Spinal cord injury surveillance in the United States: an overview. AB - In the United States, injuries are the leading cause of premature lost years of life, surpassing cancer and heart disease combined. Public health surveillance of injuries such as spinal cord injury (SCI) has recently begun to evolve, following decades of experience with similar methods for infectious and chronic disease conditions. In 1985, the Federal Government's Centers for Disease Control began to promote the development of surveillance systems for sentinel injuries at both the state and national level. Many states have developed, or are in the process of developing, statewide registries for SCI. The rationale behind the establishment of these registries is 4-fold: (1) to identify SCI persons in order to facilitate and coordinate provision of health and other services; (2) to gather accurate data for injury prevention efforts and planning for needed services; (3) to evaluate services provided, and (4) to document outcome and cost effectiveness of care systems. The purpose, content and scope of these registries are reviewed in detail. PMID- 1870890 TI - Systematic lower limb phlebography in acute spinal cord injury in 147 patients. AB - This study was concluded on paraplegic and tetraplegic patients of all aetiologies except neoplasic, where paralysis developed within 48 hours. All patients were admitted to the rehabilitation department within 90 days after the onset of paralysis. In a preliminary review of 328 files, there were 27 cases of clinical deep vein thrombosis (DVT) and 10 with pulmonary embolism (PE), 6 of which were fatal. A prospective study was conducted, based on systematic detection of asymptomatic DVT with phlebography. Among the 147 patients, 20 previously presented with DVT. The 127 others underwent phlebography which showed 39 DVT in 29 patients. Eighty seven patients with negative phlebography underwent a second study a month later which showed 14 DVT in 12 patients. Only one minor pulmonary embolism occurred in these 147 patients. The incidence of DVT after acute spinal cord injury and the frequent absence of clinical manifestations were confirmed. Prophylactic anticoagulant therapy is useful but insufficient. This study demonstrates that systematic and repeated detection of DVT by phlebography may reduce the incidence of PE. PMID- 1870891 TI - An analysis of the diverse factors concerned with the development of pressure sores in spinal cord injured patients. AB - Patients with spinal cord injuries (SCI) admitted to the Institut Guttmann, Barcelona, from the years 1985 to 1988 with pressure sores (PS) are reviewed. Demographic, pathological and psychological factors are analysed in an attempt to identify organic and/or behavioural patterns which might imply an added risk for the development of pressure sores in the spinal cord injured. About 30% of 884 SCI patients admitted during this period had one or more PS (mean 1.5), most of these were localised to the ischial, trochanteric and sacral regions, and about 70% were grade 3 or 4 (Enis and Sarmiento classification). The study supports the generally acknowledged view that a precarious state of health and certain psycho social conditions are contributing factors to a higher risk in the development and severity of PS in SCI patients. PMID- 1870892 TI - Functional electrical stimulation and reciprocating gait orthosis for ambulation exercise in a tetraplegic patient: a case study. AB - The purpose of this paper is to report the cardiopulmonary stresses (as indicated by heart rate, blood pressure, oxygen consumption and task cost) for a tetraplegic individual when walking with electrical stimulation and a gait orthosis as opposed to walking with a gait orthosis alone. Functional electrical stimulation (FES), when interfaced with a reciprocating gait orthosis (RGO), resulted in walking exercise for a C-7 level tetraplegic subject, who was 8 years post-injury. Cardiopulmonary measurements were made and task costs calculated on this individual during progressive velocity walking with the FES-RGO and the orthosis alone (without FES). Results for the tetraplegic individual indicate that there were no significant changes in heart rate at the various walking velocities with respect to the two systems. However, systolic blood pressure was significantly reduced at the three highest walking velocities (1.2, 1.6 and 2.0 kph) when using the FES and orthosis system as compared to orthosis-alone walking (p less than .025, p less than .005 and p less than .025 respectively). Calculated oxygen consumption was significantly reduced and calculated task cost improved at the highest walking velocity (2.0 kph) when using the FES-RGO system as compared to using only the RGO (p less than .025). It is concluded that cardiopulmonary stresses are significantly less for this tetraplegic individual when ambulating at the higher velocities with electrical stimulation and a gait orthosis than when walking with a gait orthosis alone. This may result in improved endurance during each walking session and (consequently) an improved aerobic exercise effect. This might also allow some tetraplegics, who would be unable to walk with the RGO alone, to walk with electrical stimulation and the RGO. PMID- 1870893 TI - Ernest H. J. Bors, MD (1900-1990). PMID- 1870894 TI - Initial factors predicting functional performance in patients with traumatic tetraplegia. PMID- 1870895 TI - Part 1. Congenital idiopathic clubfoot. AB - Although not life-threatening, clubfoot, a non-traumatic deviation of the foot, makes a strong impact on the infant, parents, and family. Serial casting with or without surgical intervention make up the medical plan. Nursing care needs to focus on emotional support of the family and education regarding the diagnosis, treatment plan, and daily care of an infant in a cast. PMID- 1870896 TI - Part 2. Osteogenesis imperfecta. AB - Osteogenesis imperfecta (OI), the most common genetic disorder of bone, is characterized by frequent, unpredictable fractures of the long bones with progressive skeletal deformity. Often diagnosed in the early years of life, OI requires a comprehensive, interdisciplinary plan of care involving patient, family, and community. The nurse's role as caregiver, educator, and patient advocate is to foster normal physical and psychosocial growth and development and minimize the opportunity for fracture. PMID- 1870897 TI - Clinical implications of the impact of autologous blood donation on functional recovery. AB - The practice of depositing units of autologous blood to prepare for elective surgery is steadily increasing. This article outlines the advantages and limitations of autologous blood donations. Secondary analysis from a study of functional recovery following total knee replacement compares functional outcomes of people who predeposited autologous units with those who did not. Clinical implications and suggestions are made for managing the patient's physiologic status during the donation process, as well as hemodynamic status during the postoperative transfusion period. PMID- 1870898 TI - Complications of lumbar spine surgery. AB - Lumbar spine surgery is now performed at all ages for reasons ranging from life threatening tumors to intractable pain. A multitude of potential complications demand astute nursing assessment skills. Though not all of the complications discussed in the following article are preventable, early recognition, intervention, and patient support by the well-educated orthopaedic nurse can significantly lessen patient morbidity and even mortality. PMID- 1870899 TI - Making a thoraco-lumbo-sacral orthosis. PMID- 1870901 TI - An exceptional teacher. PMID- 1870900 TI - Nonsteroidal antiinflammatory agents 28:08.04. PMID- 1870902 TI - Collagen vascular diseases of childhood. AB - This article is devoted to collagen vascular diseases of childhood. The connective tissue diseases that are discussed are lupus erythematosus, scleroderma, and dermatomyositis. Of the vasculitic syndromes, Henoch-Schonlein purpura, acute hemorrhagic edema of infancy, and polyarteritis nodosa are discussed. Although the collagen vascular diseases are rare in the pediatric age group, when they occur they can be very serious. PMID- 1870903 TI - Pediatric dermatology. PMID- 1870904 TI - Neonatal skin disorders. AB - Skin disorders are commonly seen in the neonatal period. A recent survey of neonates demonstrated that almost every neonate had some skin lesion. The most common skin findings are desquamation, Epstein's pearls, sebaceous hyperplasia, milia, toxic erythema, salmon patch, hypertrichosis, and Mongolian spot. In addition to these common cutaneous findings, other disorders may exist and are discussed in this article. PMID- 1870905 TI - Atopic dermatitis in infants and children. AB - Atopic dermatitis is a common, chronic inflammatory skin disease triggered by a variety of irritative emotional and allergic factors. Education and simple prevention and maintenance measures such as proper moisturizing greatly reduce disease. Antibiotics and topical corticosteroids are therapeutic mainstays. PMID- 1870906 TI - Important melanocytic lesions in childhood and adolescence. AB - Melanocytic nevi are common in children and adolescents, and the preponderance of these lesions are benign. Congenital melanocytic nevi, dysplastic nevi, and large numbers of common acquired nevi, however, may indicate an increased risk of malignant melanoma. With the exception, possibly, of giant congenital nevi, melanoma associated with these lesions generally occurs in adulthood. Nonetheless, some patients can be identified as being at increased risk for the development of melanoma during childhood. The poor prognosis associated with advanced melanoma and the curability of early lesions underscore the importance of prompt recognition of melanoma when it does occur in children. Furthermore, physicians who care for children are in a key position to decrease risk of melanoma throughout the lifespan by encouraging avoidance of excessive sun exposure during childhood. PMID- 1870907 TI - Hemangiomas and vascular malformations. AB - Vascular lesions in the neonate and infant are categorized as hemangiomas or malformations. Although their appearances may be similar, the pathobiology, natural history, and prognosis of these lesions are different. Selected important syndromes that are characterized as hemangiomas and vascular malformations are discussed, and an update on what is new in treatment, including laser therapy, is presented. PMID- 1870908 TI - All about ichthyosis. AB - From "alligator people" to "porcupine boys," the ichthyoses have been a distinctly recognizable entity for thousands of years. Recent improvements in biochemical and genetic research have allowed more scientific delineation of this class of diseases. This article covers the latest in pathophysiology, the major classes of ichthyoses, many of the newer minor ones, prenatal diagnosis, and treatment options. PMID- 1870909 TI - Childhood exanthems. Old and new. AB - Exanthems are a common cause of rashes in children. Several recent developments have sparked a renewed interest in this group of diseases, including the identification of parvovirus B19 and human herpesvirus 6 as the causative agents of erythema infectiosum and roseola infantum. The resurgence of measles as a childhood exanthem has caused a re-examination of current immunization practices. The most common and clinically significant exanthems are discussed, with an emphasis on new findings, origins, clinical manifestations, differential diagnosis, and management. PMID- 1870910 TI - Disorders of the hair and scalp in children. AB - A wide variety of disorders involving the scalp and hair exist that may be encountered in the pediatric and adolescent population. An approach to the differential diagnosis of many of these conditions can be considered once the patient is found to have either alopecia, scaling, or tumors of the scalp. Certainly other causes of scalp or hair disease exist but the more common disorders can be appropriately considered in this manner. PMID- 1870911 TI - Nail disorders in children. AB - The spectrum of nail abnormalities that may be seen in the pediatric population is discussed in this article. Developmental abnormalities, both hereditary and congenital, are discussed. Acquired nail abnormalities that may be similar to those seen in adults are also described. PMID- 1870912 TI - Diagnosis and treatment of childhood scabies and pediculosis. AB - Human scabies infestations are still a widespread occurrence. This article discusses the clinical features, infections, lesions, and sites of involvement of different types of scabies as well as pediculosis. PMID- 1870913 TI - Mucocutaneous disease in pediatric human immunodeficiency virus infection. AB - Children with HIV infection may develop a wide variety of infectious and inflammatory diseases of the skin. These disorders are often more severe and more difficult to treat than in the healthy child. In some cases, disorders of the skin or mucous membranes may provide an early clue to the presence of pediatric HIV infection. PMID- 1870914 TI - Disorders of hypopigmentation in children. AB - The most common disorders of hypopigmentation in children are pityriasis alba, vitiligo, nevus depigmentosus, and tinea versicolor. Pityriasis alba usually presents as ill defined, scaly patches of hypomelanosis on the cheeks of children with an atopic diathesis. The face is also a favored site for vitiligo, but the distribution is periorificial, and the pigment loss is complete because of a destruction of melanocytes. Vitiligo is an acquired, progressive disorder in contrast to nevus depigmentosus, which is a stable, congenital leukoderma. The localized form of nevus depigmentosus must be distinguished from an ash leaf spot, the earliest cutaneous manifestation of tuberous sclerosis, whereas the systematized form may be confused with hypomelanosis of Ito, another neurocutaneous disorder. The lesions of tinea versicolor favor the upper trunk of adolescents, and potassium hydroxide examination of the associated scale reveals hyphal and yeast forms of P. orbiculare. Any inflammatory process in the skin such as dermatitis or psoriasis can resolve with areas of hypopigmentation. PMID- 1870915 TI - Intracranial tuberculosis in children: CT appearance and clinical outcome. AB - We retrospectively evaluated the CT studies of 9 children who presented with intracranial tuberculosis during 1981-1987, and compared their radiographic appearance with the clinical outcome. The most common radiographic findings were: 1) ventriculomegaly (7/9) ,2) tuberculoma formation (6/9), and 3) infarction (4/9). Of 7 patients with ventriculomegaly, 3 required a ventricular shunt and 2 had spontaneous resolution of ventricular dilatation. Four children with ventriculomegaly were moderately or severely retarded, one had cognitive dysfunction, and one was neurologically normal. Four of six children with tuberculoma also had infarction and/or ventriculomegaly; of these four children, three were moderately or severely retarded. Two patients with tuberculoma as the only intracranial abnormality had complete resolution of the granuloma with normal neurologic outcome following antituberculous therapy. The four children with large vessel infarction also had ventriculomegaly; three had poor clinical outcome. The presence of tuberculoma alone is not necessarily predictive of poor neurologic outcome; age less than 20 months, infarct, and/or ventriculomegaly are usually associated with sequelae. PMID- 1870916 TI - Height of normal pituitary gland as a function of age evaluated by magnetic resonance imaging in children. AB - MR anatomy of hypothalamo-hypophyseal axis is well established. However data about pituitary gland height (PGH) in children are sparse. A retrospective study was therefore performed in 60 children (30 boys and 30 girls) aged from 8 days to 21 years. All these children had MR for various neurological diseases. Patients with hypothalamo-hypophyseal disease and intracranial hypertension were excluded. The PGH was measured on a strict midline sagittal T1 weighted scan 3 to 7 mm thick. A positive linear correlation was found in children aged from 1 year to puberty followed by a plateau. In the first year of life a negative linear correlation was found. A positive linear correlation was found between PGH and statural height as well. PMID- 1870917 TI - Sonographic abnormalities of the thyroid gland in longterm survivors of Hodgkin disease. AB - We studied the thyroid gland in 18 long term survivors of Hodgkin Disease, all of whom received radiation therapy (2400-4000 cGy, mean 3434). Evaluation included clinical examination, thyroid function tests, ultrasound, as well as selective use of nuclear scintigraphy. The time interval post radiation was 1-16 years (mean 6.4 years). Clinical evaluation and thyroid function tests were insensitive in detecting abnormalities and most nodules were non palpable. Ultrasound detected abnormalities in 16 patients (89%) including diffuse atrophy (n = 6), solitary nodules (n = 4), multiple nodules (n = 5) and gland heterogeneity with calcification in one patient. Cold nodules on nuclear scintigraphy (n = 4) were subjected to biopsy. Multiple foci of papillary carcinoma were found in one patient. There was a tendency for nodules to increase in number as the post radiation interval also increased. We recommend frequent sonographic evaluation and early suppression of thyroid stimulation in an attempt to arrest the development of neoplastic changes. PMID- 1870918 TI - Percutaneous needle aspiration of neonatal lung abscesses. AB - Three premature infants (mean gestational age 27 weeks) ranging in age from 3 to 11 weeks, were treated for lung abscesses, with a combination of antibiotics and percutaneous needle aspiration under either ultrasound or fluoroscopic guidance. Antibiotics, to which microorganisms cultured from aspirated pus were sensitive, were continued for a further period of two weeks, with no relapse in any of the patients. The lung abscesses resolved in all cases without the need for catheter drainage or surgery. In conclusion, needle aspiration under either ultrasound or fluoroscopic guidance is a simple and effective diagnostic and therapeutic method of managing neonatal lung abscesses. Its early use allows selection of the most appropriate antibiotics and may hasten recovery, prevent further complications and obviate the need for surgery. The use of a drainage catheter does not appear to be necessary for resolution of the abscesses. The procedure appears reasonably safe, since complications arising from the procedure were benign. PMID- 1870919 TI - The role of the accessory pancreatic duct of Santorini in pancreatic drainage in children (with emphasis on choledochal cyst patients). AB - Pancreatic drainage patterns have been studied by endoscopic retrograde cholangiopancreatography (ERCP) in four children with choledochal cyst (CC). The first two had mild or chemical pancreatitis; the third had a history of recurrent cholangitis and was diagnosed as chronic pancreatitis. The fourth manifested with severe, acute pancreatitis. All children were found to have an impaired flow through the papilla of Vater. In the first three cases, the duct of Santorini (DS) seemed to play an important role in the pancreatic drainage. In the fourth case, however, the duct was found to be absent. ERCP findings in additional eleven children without CC also were reviewed, and in this group the DS did not seem to play any significant role in pancreatic drainage. These results indicate that in children with common bile duct (CBD) anomalies, the DS may relieve the obstruction and ameliorate the pancreatitis. PMID- 1870920 TI - The swallowed toothbrush: a radiographic clue of bulimia. AB - Swallowed toothbrushes were noted in the esophagus of one teenager and the stomach of two others with bulimia. The presence of a toothbrush in the lumen of the gastrointestinal tract should make the radiologist suspicious of bulimia/anorexia nervosa. A toothbrush shows a characteristic radiographic image with parallel rows of short metallic radiodensities due to the metallic plates that hold the bristles in place. PMID- 1870921 TI - Umbilical vein draining into the inferior vena cava via the internal iliac vein, bypassing the liver. AB - This is the third report of an anomalous umbilical vein draining ectopically in a left pelvic vein, probably the left internal iliac, and through the inferior vena cava into the right atrium. The anomaly was encountered in a newborn infant with nonimmune hydrops fetalis, hypertrophic cardiomyopathy, multiorgan failure and possibly Noonan Syndrome. PMID- 1870922 TI - "Dilatation" of the left renal vein on computed tomography in children: a normal variant. AB - Compression of the left renal vein (LRV) between the superior mesenteric artery and the aorta is thought to be a cause of hematuria, periureteral and gonadal varices, and varicocele ("Nutcracker phenomenon"). Previous investigators have suggested that this diagnosis can be made on computed tomography when the LRV ratio greater than or equal to 1.5 (the diameter of the LRV proximal to the aorto mesenteric angle divided by the diameter of the LRV distal to the aorto mesenteric angle). This study was designed to establish the normal range for the LRV ratio on CT in children. The LRV ratio was measured in thirty-nine consecutive children undergoing intravenously enhanced CT of the abdomen. None of the children had hematuria on urinalysis immediately before or after the CT. Children with any known abnormality involving the kidneys, adrenal glands, IVC, or renal or gonadal veins were excluded. The patients ranged in age from 3.4 to 18.5 years (mean = 10.6 years). LRV ratio ranged from 0.78 to 2.00 (mean = 1.46; S.D. = 0.312). Twenty of the 39 children (51.3%) had a LRV ratio greater than or equal to 1.50. The conclusion is that the normal range for the LRV ration is too wide for it to be useful in diagnosing LRV entrapment and that a LRV ratio greater than or equal to 1.5 on CT is normal in children. PMID- 1870923 TI - Pyramidal hyperechogenicity in autosomal recessive polycystic kidney disease resembling medullary nephrocalcinosis. AB - Striking pyramidal hyperechogenicity resembling the sonographic appearance of medullary nephrocalcinosis was found in autosomal recessive polycystic kidney disease (ARPKD). This sonographic pattern is distinctly different from those described previously in ARPKD. PMID- 1870924 TI - Antenatal diagnosis of renal pelvic dilatation--the natural history of conservative management. AB - Seventy children with an antenatal diagnosis of unilateral renal pelvic dilatation underwent Tc 99 m DTPA diuretic renograms. There were 16 kidneys with moderate function, and 54 with good function, 31 underwent pyeloplasty, all had a renal pelvis greater than 12 mm diameter on ultrasound. Thirty nine children with good function were treated conservatively. Long term follow up has demonstrated that conservative management for PUJ dilatation with a good functioning kidney may be justified but a randomised control study is required. PMID- 1870925 TI - Renal obstructive dysplasia: ultrasound diagnosis and therapeutic implications. AB - 57 cases of renal obstructive dysplasia (defined as the abnormal development of nephronic and ductal structures due to in utero obstruction of the urinary tract) were evaluated in terms of sonographic findings, renal and other associated anomalies, and current status of the child. More than one-third of the cases had bilateral disease and although not uniformly fatal bilateral involvement was associated with significant morbidity and mortality. In 12 of the 33 cases with unilateral dysplasia there was an association with contralateral renal problems including uretero-pelvic junction obstruction, vesicoureteral reflux and aplasia. Almost one-half of the cases had congenital anomalies, these included VACTERL association, congenital heart disease, cranial abnormalities and gastrointestinal malformations. Fifteen stillborns and 12 of the patients with bilateral involvement and four with unilateral involvement have died. Four patients are on dialysis (two with bilateral involvement and two with unilateral renal obstructive dysplasia). Only one-quarter are otherwise normal. More serious problems are reported in this mixed age population of patients with obstructive renal dysplasia than has been identified in previous studies. Management decisions of the fetus and child must be based on this new age-expanded population. PMID- 1870926 TI - Urethral morphology and bladder instability. AB - In order to calculate the relationship between Spinning top urethra (STU) and bladder instability 160 voiding cystourethrogramms (VCU), performed in 102 girls, have been analysed retrospectively. 28 girls had STU, 16 of those had bladder instability as well (57%). We could not find the highly positive correlation between unstable bladder and STU as reported by other authors, although there was a statistically positive correlation between STU and bladder instability. However the confidence interval was very broad (38%-75%). We conclude that bladder instability may contribute to STU but cannot render the etiological explanation for all cases. STU seems to be a polyetiological sign. In our opinion only the combination of STU and bladder instability has a diagnostic impact, since several therapeutical concepts are available in cases of bladder instability. The finding of STU in the VCU should alert the examiner's attention to functional disorders of the lower urinary tract. If no instability can be found, STU should be considered to be a normal variant. PMID- 1870927 TI - MRI in distal vaginal atresia. AB - Magnetric resonance imaging in two young females with abdominal pain revealed vaginal atresia with massive hematocolpos but a normal cervix and uterine body. Information obtained with MRI was superior to ultrasound and CT and is suggested as the examination of choice prior to surgical correction. PMID- 1870928 TI - Testicular adrenal-like tissue (TALT) in congenital adrenal hyperplasia: detection by ultrasonography. AB - In a consecutive series of 15 male adolescents and young adults with congenital adrenal hyperplasia (CAH), the size, shape, firmness and echostructure of the testes were assessed. The latter was abnormal in 7 patients under long standing treatment with glucocorticoids (group I). In 8, 5 under and 3 off treatment for several years, ultrasonography (US) was normal (group II). On the basis of the US findings the patients were placed in two groups. In group I, the testes had a heterogeneous ultrasonographic pattern; clinically, most felt hard and irregular, although their volume was normal. Sperm count in 3 patients was 5.0 to 14.4 x 10(6)/ml. Five patients have 21-hydroxylase deficiency that was diagnosed in early infancy and had salt-wasting; two have 11-beta-hydroxylase deficiency that was diagnosed late and had no salt-wasting. In group II, testicular volume, shape, firmness and echostructure were normal. All have 21-hydroxylase deficiency, no history of salt-wasting and were diagnosed late. Sperm counts in 3 patients off treatment were 10.5 to 66.0 x 10(6)/ml. In severe cases with a history of salt loss, TALT with deficient spermiogenesis seems likely despite treatment. In mild cases, TALT is absent and spermiogenesis may be normal even without treatment. US is much more accurate in assessing the testes than palpation. PMID- 1870929 TI - Ultrasound in advanced pediatric osteomyelitis. A report of 5 cases. AB - The use and reporting of ultrasound for the evaluation of pediatric osteomyelitis is minimal. However, ultrasound is noninvasive and does not employ ionizing radiation, and it is less expensive than other methods available. Consequently, its application, if contributory, would be desirable in evaluating pediatric osteomyelitis. We examined five patients ranging from 2-weeks to ten-years-old with ultrasound after bony abnormalities were found on plain film. In all cases ultrasound was valuable in assessing the type and location of abnormality (4 cases of osteomyelitis, 1 case of discitis), but unhelpful in determining the age of disease. PMID- 1870930 TI - MR appearances of bone marrow in children following bone marrow transplantation. AB - Two cases are presented of children who demonstrated complete absence of bone marrow signal on MR imaging of the spine following bone marrow transplantation. The possible causes for these appearances are discussed. PMID- 1870931 TI - The spondylometaphyseal dysplasias. A tentative classification. AB - The spondylometaphyseal dysplasias constitute a very complex group of disorders. In addition to the Kozlowski type, three subgroups can be distinguished by the appearance of the femoral neck. In the first group (A) the changes are severe with absent ossification of the femoral neck and coxa vara. In the second group (B) the changes of the femoral neck are moderate and in the third (C) mild metaphyseal irregularities are only visible. This classification is not definitive but tries to put order in this confusing section of constitutional bone diseases. PMID- 1870932 TI - Spondylometepiphyseal dysplasia congenita, Strudwick type. AB - A case of spondylometepiphyseal dysplasia congenita, Strudwick type is presented. At birth, this condition cannot be distinguished from spondyloepiphyseal dysplasia congenita. Features in common include delayed ossification of the public bones and proximal femoral epiphyses, coxa vara, odontoid hypoplasia and lumbar lordosis. The distinguishing radiologic feature of this condition is the striking irregularity of long bone metaphyses which develops during infancy. PMID- 1870933 TI - Pediatric yaws osteoperiostitis. PMID- 1870934 TI - C.T. findings in the Hajdu-Cheney syndrome. AB - We describe a patient with the typical features of Hajdu-Cheney Syndrome. The previously undescribed cranial computerised tomographic (C.T.) findings in this condition are discussed. In addition we describe a possible association with bowel malrotation. PMID- 1870935 TI - Detection of a radiolucent bronchial foreign body by computed tomography. PMID- 1870936 TI - Enteric fistula formation secondary to necrotizing enterocolitis. AB - We report two cases of enterocolonic fistula formation following necrotizing enterocolitis, and a review of the six previously published cases. Ischemic mechanism is the most likely cause. The fistulas were diagnosed by upper gastrointestinal series and contrast enema. PMID- 1870937 TI - Sonographic evaluation of renal artery aneurysm in childhood. AB - We report a child presenting with renovascular hypertension and sonographic evidence of a renal artery aneurysm (RAA). The diagnosis of RAA was made sonographically by demonstrating vascular flow in an aneurysmal segment adjacent to but continuous with the right renal artery and externally compressing the inferior vena cava. Comparison of the sonographic studies and an abdominal angiogram illustrate the sensitivity of sonography in diagnosing this condition. We suggest that with renal doppler sonography, RAA may be diagnosed less invasively and possibly with greater frequency yet believe that the gold standard of angiography is necessary prior to surgical intervention. PMID- 1870938 TI - Diffuse intestinal arteriovenous malformation in a child. AB - Mesenteric arteriovenous fistulas or arteriovenous malformations of the intestine are relatively rare, especially in the form of diffuse disease. We describe a case of diffuse intestinal arteriovenous malformation associated with congestive heart failure and cutaneous hemangioma. PMID- 1870939 TI - Sibs with a disorder resembling Blount disease (tibia vara). AB - Radiographic investigation of 3 Turkish sibs presenting with bowed legs disclosed physiological tibial bowing in the 7-month-old girl. Stage I Blount disease in the 26 month-old boy and Stage II Blount disease in the 45 month-old girl. The reported cases provide evidence for autosomal recessive inheritance. This observation points to genetic heterogenity, i.e. the existence of 2 genetically different, but radiologically indistinguishable disorders. PMID- 1870940 TI - Dandy-Walker malformation, cranial meningocele, ocular abnormalities, and cleft palate: Walker-Warburg syndrome? PMID- 1870941 TI - The "candlestick sign" on cerebral ultrasound. PMID- 1870942 TI - A new series of 2,2'-bipyridyl analogues with high activity against AIDS complicating micro-organisms. PMID- 1870943 TI - Fluconazole. Review and situation among antifungal drugs in the treatment of opportunistic mycoses of human immuno-deficiency virus infections. AB - Fluconazole is a novel triazole antifungal drug chiefly used in the treatment of opportunistic mycoses in immuno-compromised patients, particularly those with the acquired immuno-deficiency syndrome (AIDS). In comparison with other antifungal drugs, fluconazole has outstanding physical and pharmacokinetic properties, such as an excellent aqueous solubility allowing a parenteral formulation, high bioavailability by the oral route, even distribution throughout the tissues, including the central nervous system and the cerebro-spinal fluid, a long half life (permitting once daily administration), and low binding to plasma proteins. It is excreted mainly as unchanged drug in the urine. Fluconazole is a broad spectrum antifungal agent, especially effective against Candida spp., Cryptococcus neoformans and dermatophytes. Its antifungal efficacy was mainly proved by testing in animal models, since there is no relationship between in vitro and in vivo activities. It possesses a low toxicity and it is well tolerated. Fluconazole is currently marketed for the treatment of oropharyngeal candidiasis in immuno-compromised patients and of atrophic oral candidiasis. Its place in the treatment of opportunistic mycoses in human immuno-deficiency virus positive patients, in particular cryptococcal meningitis, is still under investigation but is promising. PMID- 1870944 TI - Antiviral drugs. AB - There are only a limited number of effective, non-toxic antiviral drugs for clinical use, whereas there is a great need for such drugs. Especially for the treatment of patients infected with the human immuno-deficiency virus (HIV) anti HIV drugs are required. At the same time viral infections secondary to AIDS cannot yet be treated effectively. An increasing problem is the development of virus strains resistant to the available drugs. At this moment a great effort is made in the research for new antiviral drugs. In this article the available antiviral drugs are reviewed. Their antiviral properties, mechanism of action, clinical use, pharmacokinetic properties and side-effects are discussed. Some attention is paid to the future directions in the search for new anti-HIV drugs. PMID- 1870945 TI - Distribution of naturally occurring quinones. AB - Angiosperms, fungi (including lichens), and bacteria are the main sources of natural quinones. Small numbers are present in algae, ferns, conifers, sponges, echinoderms, other marine animals, and arthropods. In angiosperms quinones have some chemotaxonomic value at the genus and family level but more surveys are required. PMID- 1870946 TI - Biotechnology and biosynthesis of quinones. AB - Nowadays, it is generally agreed that intensive investigation of biosynthetic pathways is a prerequisite for attaining industrial-scale production of secondary metabolites (e.g. quinones) by plant cell cultures. Literature data are presented to illustrate different aspects of today's quinone biosynthesis research. PMID- 1870947 TI - Evaluation of genotoxic risk of handling cytostatic drugs in clinical pharmacy practice. AB - The genotoxic risk of handling antineoplastic drugs was evaluated in fifteen women preparing chemotherapeutics in the Pharmacy Department of the University Hospital Maastricht. Twenty nurses of the same hospital, who were not exposed to cytostatics, acted as controls. Endogenous exposure to antineoplastic drugs was assessed by determination of urine mutagenicity, as well as by analysis of urinary methotrexate levels. As genotoxicological end-points, sister chromatid exchanges and hypoxanthine guanine phosphoribosyl transferase locus point mutations were studied in peripheral lymphocytes obtained via venous puncture. No differences in urine mutagenic activity, in sister chromatid exchange frequencies and in hypoxanthine guanine phosphoribosyl transferase point mutation frequencies between exposed and non-exposed groups were detected. Higher sister chromatid exchange frequency was observed in smokers as compared to non-smokers. PMID- 1870948 TI - Direct high pressure liquid chromatographic analysis and preliminary pharmacokinetics of enantiomers of oxazepam and temazepam with their corresponding glucuronide conjugates. AB - Three high pressure liquid chromatographic systems for the separation of oxazepam, temazepam and their glucuronides (system A), the separation of their R,S glucuronide diastereomers (system B) and the chiral separation of the parent drugs (system C) are described. Preliminary pharmacokinetics of R,S-oxazepam and R,S-temazepam in a human volunteer reveal that the protein binding of the glucuronides is lower than that of the parent drugs, but that there is no difference in protein binding between the R-oxazepam/temazepam and S oxazepam/temazepam and their corresponding glucuronides. The S-glucuronide is the main metabolite formed and excreted by man. The plasma ratio R/S-glucuronide is 1:1 for both oxazepam and temazepam. The renal clearance of R-temazepam, and S temazepam are similar, and those of R-oxazepam and S-oxazepam tend to be different. PMID- 1870949 TI - Comparison of questionnaire information and pharmacy data on drug use. AB - Information on chronic drug use at any time in the past was collected with a self administered questionnaire as part of a prospective cohort study on diet, other life-style factors and cancer among subjects aged 55-69 years. The validity of the questionnaire information on drug use was evaluated among 207 subjects by comparing it to pharmacy records of dispensed drugs. The comparison could be made for the 2.5-year period preceding the questionnaire administration. Since the study subjects did not mention prescription drugs that were not dispensed by their pharmacy, indicating no errors of commission, the analyses were focused on the estimation of sensitivity of drug recall and its correlates. Questionnaire recall of drug use amounted overall to 61.2% of drugs prescribed to the subjects for at least 6 months. Drug recall decreased with increasing age and with increasing number of prescribed chronic use of drugs per subject. No difference in recall was observed between men and women. Recall tended to improve with increasing duration of use and varied with type of drug. When only long-term drug use at the time of questionnaire administration was considered, overall recall of drug use was 68.8%. PMID- 1870950 TI - Markers of adverse drug reactions in medication histories. An analysis of inhaled steroid utilization. AB - Prescription sequence analysis is based on the observation that a subset of adverse drug reactions are themselves indications for the prescription of another drug. We propose an approach to the analysis of clustering of prescriptions in medication histories that contain records of a presumed side-effect-causing drug A and a side-effect-alleviating drug B. This set of histories with records of both A and B is analysed in a logistic regression model that considers the start of B against exposure and non-exposure of A, stratified on the level of the individual histories. A correction is presented for the periods of B use, during which a new start of B cannot occur. Prescription sequence analysis is demonstrated with a set of histories of use of inhaled steroids (A) and topical oral anticandida drugs (B). A can cause oral candidiasis, B is therapy for this condition. An odds ratio of 1.43 was found for the association of A use and the initiation of therapy with B. PMID- 1870951 TI - [MR studies of extension and spread pattern of nasopharyngeal carcinoma]. AB - Seven patients with T2-T4 nasopharyngeal carcinoma were examined by MRI on a 0.5T superconducting system. The obtained MRI images were reviewed focusing on the signal intensity (SI) of tumors, and the extension of tumors into the related spaces from the pharyngeal mucosal space (PMS). Consequently, the SI of tumors demonstrated low on T1 weighted images and high on T2 weighted images. The parapharyngeal space was the first space where the tumors extended from the pharyngeal mucosa. The parapharyngeal space was an intermediate point of extension to the masticator space (MS), the carotid space (CS), the retropharyngeal space (RPS), and the prevertebral space (PVS). The PVS involvement by tumors was not a direct extension from the PMS, because the posterior portion of pharyngobasilar fascia worked as a barrier on MR. Therefore, the longus capitus muscle in the prevertebral space was considered to be involved via the parapharyngeal space (PPS). The masticator space involvement was indicated by slightly high SI of pterygoid muscle on T2 weighted images, and also the effacement of the PPS fat and parapharyngeal venous plexus were considered as a sign of involvement into the masticator space. The retropharyngeal lateral lymph node (Rouviere) metastases were recognized by MR. These metastasized lymph nodes were low on T1 weighted images and high on T2 weighted images. PMID- 1870952 TI - [Three-dimensional CT imaging of the small lung cancer--a trial using an inflated fixed lung specimen]. AB - In order to examine clinical usefulness of three-dimensional (3D) imaging of solitary pulmonary nodules froms serial thin-section CT images, 3D reconstruction of a small peripheral lung adenocarcinoma was performed using the inflated fixed lung specimen resected surgically. The left upper lobe was fixed and air-dried by Heitzman's method, and was scanned contiguously 20 times at a section thickness of 2 mm and a section interval of 2 mm. Bronchi, pulmonary vessels and the tumor presented on the CT images were input to a 3D reconstruction personal computer system, and then 3D images were obtained. The reconstructed 3D images included various tomographic images of bronchi and pulmonary vessels. It is expected that this method would be one of the most useful imaging techniques for the differential diagnosis of solitary pulmonary nodules. PMID- 1870953 TI - [CT appearance of small renal angiomyolipoma]. AB - Twenty-six small renal angiomyolipomas (AML) in 21-patients, detected incidentally by ultrasonography, were evaluated with CT. Conventional CT findings of AML were classified into three types by the degree of the fatty areas in the mass. Type 1 is a mainly fat density mass like a lipoma observed in 7 lesions (26.9%). Type 2 is a fatty mass intermixed with areas of tissue density and found in 15 lesions (57.7%). Type 3 is a mass without fatty portion and observed in 4 lesions (15.4%). These latter lesions were indistinguishable from renal cell carcinoma on CT. It is important to diagnose a small lesion of the kidney as AML correctly for proper treatment. PMID- 1870954 TI - [Magnetic resonance imaging of the inner ear and its application to cochlear implant candidates]. AB - Magnetic resonance (MR) images of normal and abnormal inner ears obtained with a 1.5T unit without the use of a surface coil were analyzed to evaluate the effectiveness of this method in the screening of cochlear implant candidates. In a series with sixteen normal adult volunteers, 22 to 45 years in age, 100% of the cochleae, vestibules, and lateral and posterior semicircular canals were clearly demonstrated in T2 weighted images. Satisfactory images were not obtained for 22% of the superior semicircular canals, 22% of the cochlear aqueduct, and 81% of the vestibular aqueduct in axial images, but coronal and sagittal reconstructed images by use of a three-dimensional Fourie transformation sequence provided better detectability of these structures. In five ear surgery patients with proven obliteration of the labyrinth, decreased signal intensity was observed in the T2 weighted images. Ten cochlear implant candidates were examined by MRI prior to implantation, and the results were compared with the surgical findings. In two ears in which the cochlea showed a decrease in signal intensity, the cochlea had been obliterated by inflammatory granulations. On the other hand, the lumens of all nine cochleae which were clearly visualized by MRI were found to be patent. PMID- 1870955 TI - [Computed tomographic evaluation of thickness of perirectal fascia in rectal cancer treated by preoperative radiotherapy--diagnostic value for prediction of local recurrence]. AB - Perirectal fascia was examined by computed tomography before and after preoperative radiotherapy in thirty-six patients with rectal cancer. CT measurement showed that perirectal fascia tend to increase in thickness during preoperative radiotherapy in proportion to tumor extension into perirectal fat tissue. The fascial thickening more than 7 mm after preoperative radiotherapy was suggestive of local recurrence to develop. Preoperative or intraoperative boost irradiation would be recommended for such high-risk patients. PMID- 1870956 TI - [Clinical value of thallium-201 reinjection after delayed imaging in patient showing incomplete or no redistribution]. AB - To asses clinical value of Tl-201 (Tl) reinjection after delayed imaging, 30 patients who showed incomplete or no redistribution in stress-delayed Tl myocardial scintigraphy were studied. Of 76 myocardial segments with incomplete or no redistribution on the delayed images, 29 segments (38%) showed improvement of Tl uptake after Tl reinjection. Reinjection was considered effective in 24 segments (32%) where no or little redistribution were observed on the delayed images but improved after reinjection. The contrast ventriculography showed less wall motion abnormality in the segments with improvement after reinjection than that without improvement after reinjection (regional wall motion score: 2.55 +/- 0.50 vs. 0.59 +/- 0.97 p less than 0.01). History of myocardial infarction was also significantly less in the former (p less than 0.05). We conclude that Tl reinjection is useful in cases showing no or equivocal redistribution on the delayed images. PMID- 1870957 TI - Surgical and prosthetic reconstruction of severely resorbed maxillae with autogenous bone grafts and immediately placed dental implants. PMID- 1870958 TI - Extensive endodontic involvements following herpes zoster attack to facial area; report of a case. PMID- 1870959 TI - A short course on risk management: dental malpractice. PMID- 1870960 TI - In vivo mercury and methyl mercury levels in patients at different intervals after amalgam restorations. PMID- 1870961 TI - Dental practice productivity and the aging patient. PMID- 1870962 TI - How to detect decay in your dental practice. PMID- 1870963 TI - Compilation and alignment of DNA polymerase sequences. PMID- 1870964 TI - Transcript mapping reveals different expression strategies for the bicistronic RNAs of the geminivirus wheat dwarf virus. AB - We have characterised the major transcripts of the Czech isolate of wheat dwarf virus (WDV-CJI) which show that WDV uses two different mechanisms for expressing overlapping open reading frames (ORFs). Mapping of the virion sense RNAs identified a single polyadenylated transcript of 1.1kb spanning the overlapping ORFs V1 and V2 which encode cell-cell spread functions and the coat protein respectively. This finding distinguishes WDV from other monocot-infecting geminiviruses studied so far which were shown to encode two 3' co-terminal transcripts capable of expressing either the V1 or V2 ORF. A survey of codon usage at the junction between the V1 and V2 ORF has led us to propose that translational frame shifting analogous to that in the yeast Ty element may occur. Analysis of polymerase chain reaction (PCR) amplified complementary sense cDNA clones has revealed the presence of mature spliced and unspliced RNAs which could encode products of an intron mediated C1:C2 ORF fusion or the C1 ORF product alone. Mapping of the 5' and 3' extremities of the major WDV encoded transcripts has allowed us to identify putative transcription regulatory sequences and the presence of multiple overlapping transcripts may suggest temporal regulation of transcription. PMID- 1870965 TI - Isolation of estrogen receptor-binding sites in human genomic DNA. AB - Total genomic DNA digested by restriction enzymes was mixed with the DNA-binding domain of the estrogen receptor (ER-DBD) that was expressed in Escherichia coli and the fragments that bound to it were selected by nitrocellulose filter. These fragments were cloned into a plasmid vector and amplified. This selection process was repeated six times and five fragments ranging from 0.2 to 2 kb were isolated. Interestingly, each of these fragments had a perfect palindromic estrogen responsive element (ERE) (GGT-CANNNTGACC). More surprisingly, one of the fragments was found to be derived from the same locus as a fragment obtained by another similar but independent experiment. The results indicate that the ER-DBD region can bind by itself specifically to the perfect palindromic ERE with a 3 base pair spacing but it does not bind strongly enough to the half palindromic EREs or to the imperfect palindromic EREs. Chloramphenicol acetyltransferase assay has shown that some of these fragments have estrogen-dependent enhancer activity, suggesting the existence of a target gene near these fragments. The method described here may be generally applicable for screening and isolation of other transcription factor-binding sites in genomic DNA. PMID- 1870966 TI - Fluorescent-labeled oligonucleotide probes: detection of hybrid formation in solution by fluorescence polarization spectroscopy. AB - Fluorescein-labeled oligonucleotides as DNA-probes were synthesized and used to monitor hybrid formation, namely to detect DNA or oligonucleotide sequence in solution. The introduction of fluorescein to oligonucleotides was carried out by oxidation of a hydrogen phosphonate linkage with ethylenediamine or hexamethylenediamine as a tether and by a subsequent labeling of the primary amine moiety by FITC. Fluorescence anisotropy, r, was adopted as an index to monitor the behavior of F-probe in solution. An increase in the anisotropy was observed upon an increase in the chain-length of F-probe. When F-Probe formed a hybrid with its complementary oligonucleotide in solution, the r value increased compared to that of F-Probe itself. These observations clearly indicate that measurements of r in solution will readily lead to the monitoring of the presence of a hybrid in solution. Consequently, it is promising to detect a certain nucleic acid sequence in solution using fluorescent-labeled oligonucleotides. PMID- 1870967 TI - Bending of synthetic bacteriophage 434 operators by bacteriophage 434 proteins. AB - The extent of DNA bending induced by 434 repressor, its amino terminal DNA binding domain (R1-69), and 434 Cro was studied by gel shift assay. The results show that 434 repressor and R1-69 bend DNA to the same extent. 434 Cro-induced DNA bends are similar to those seen with the 434 repressor proteins. On approximately 265 base pair fragments, the cyclic AMP receptor protein of Escherichia coli (CRP) produces larger mobility shifts than does 434 repressor. This indicates that the 434 proteins bend DNA to a much smaller extent than does CRP. The effects of central operator sequence on intrinsic and 434 protein induced DNA bending was also examined by gel shift assay. Two 434 operators having different central sequences and affinities for 434 proteins display no static bending. The amount of gel shift induced by 434 repressor on these operators is identical, showing that the 434 repressor bends operators with different central sequences to the same extent. Hence, mutations in the central region of the operator do not influence the bent structure of the unbound or bound operator. PMID- 1870968 TI - Rapid DNA sequencing by horizontal ultrathin gel electrophoresis. AB - A horizontal polyacrylamide gel electrophoresis apparatus has been developed that decreases the time required to separate the DNA fragments produced in enzymatic sequencing reactions. The configuration of this apparatus and the use of circulating coolant directly under the glass plates result in heat exchange that is approximately nine times more efficient than passive thermal transfer methods commonly used. Bubble-free gels as thin as 25 microns can be routinely cast on this device. The application to these ultrathin gels of electric fields up to 250 volts/cm permits the rapid separation of multiple DNA sequencing reactions in parallel. When used in conjunction with 32P-based autoradiography, the DNA bands appear substantially sharper than those obtained in conventional electrophoresis. This increased sharpness permits shorter autoradiographic exposure times and longer sequence reads. PMID- 1870969 TI - Site-directed mutagenesis of hepatocyte nuclear factor (HNF) binding sites in the mouse transthyretin (TTR) promoter reveal synergistic interactions with its enhancer region. AB - The transthyretin (TTR) gene is regulated by two DNA regions which elicit hepatocyte-specific expression: a proximal promoter and distal enhancer. The TTR promoter and enhancer are composed of at least eight DNA binding sites for three different hepatocyte nuclear factors (HNF), CCAAT/enhancer binding protein (C/EBP), and AP-1/cJun. Site directed mutations within each of the HNF binding sites in the TTR promoter were introduced to evaluate their contribution to transcriptional activity in hepatoma cells. The data indicate that the strong affinity HNF-3-S binding site (-106 to -94) is absolutely required for TTR promoter activity since several mutations in this site eliminate TTR expression in the context of its enhancer. Conversion of a second weak affinity HNF3-W site (-140 to -131) in the TTR promoter to a high affinity site resulted in higher levels of expression. TTR mutations that disrupted several weak affinity sites (HNF1, HNF3-W, and HNF4) only slightly diminished expression levels in the presence of the TTR enhancer. In contrast, when we deleted the TTR enhancer from these HNF mutant constructs, TTR expression decreased to undetectable levels. This result suggests cooperation between the factors binding to the TTR promoter and enhancer regions. These results also demonstrate that the HNF3-S site alone is not sufficient to activate TTR transcription, but rather requires the participation of three cell-specific factors to elicit minimal promoter activity. The complexity of this promoter design and the requirement for a minimal number of cell-specific factors to achieve transcription allows us to propose a model which may explain the maintenance of tissue-specific expression of TTR. PMID- 1870970 TI - Characterization of human 5S rRNA genes. AB - The human 5S rRNA genes are found in clusters of tandem repeated units. We have cloned and partially characterized six restriction fragments from two clusters of 2.3 kb and 1.6 kb repeats, respectively. Four fragments from the cluster of 2.3 kb repeats contain a 5S rRNA gene and one fragment contains a gene variant with an additional nucleotide in the internal control region. A fragment from the 1.6 kb cluster contains a gene and is highly homologous to the 2.3 kb repeats, except for a large deletion in the 3'-flanking region starting 12 bp downstream of the gene. The number of genes and closely related gene variants is found to be 300 400 per haploid human genome. 100-150 of these are found in 2.3 kb repeats and 5 10 are found in 1.6 kb repeats. The total number of 5S rRNA sequences, including pseudogenes, is 1700-2000 per haploid genome. The genes and the gene variant are transcribed equally efficient in a HeLa cell extract. If 5'-flanking sequences, including a GC-motif in the -40 region, are removed from the genes, transcription is reduced with a factor 10 or more, suggesting that sequences upstream of the coding region are important for the level of transcription. PMID- 1870971 TI - The FIS protein binds and bends the origin of chromosomal DNA replication, oriC, of Escherichia coli. AB - The FIS protein (factor for inversion stimulation) is known to stimulate site specific recombination processes, such as the inversion of the G segment of bacteriophage Mu, by binding to specific enhancer sequences. It has also been shown to activate transcription from rRNA promoters both in vitro and in vivo. We have identified a specific binding site for FIS in the center of the origin of chromosomal DNA replication, oriC. The DNA bends upon FIS binding. Occupation of the FIS site and binding of DnaA, the initiator protein, to its adjacent binding site (R3) are mutually exclusive. A fis mutant strain can not be efficiently transformed with plasmids which carry and replicate from oriC, suggesting that FIS is required for minichromosome replication. PMID- 1870972 TI - Identification and sequence analysis of a methylase gene in Porphyromonas gingivalis. AB - A gene from the periodontal organism Porphyromonas gingivalis has been identified as encoding a DNA methylase. The gene, referred to as pgiIM, has been sequenced and found to contain a reading frame of 864 basepairs. The putative amino acid sequence of the encoded methylase was 288 amino acids, and shared 47% and 31% homology with the Streptococcus pneumoniae DpnII and E. coli Dam methylases, respectively. The activity and specificity of the pgi methylase (M.PgiI) was confirmed by cloning the gene into a dam- strain of E. coli (JM110) and performing a restriction analysis on the isolated DNA with enzymes whose activities depended upon the methylation state of the DNA. The data indicated that M.PgiI, like DpnII and Dam, methylated the adenine residue within the sequence 5'-GATC-3'. PMID- 1870973 TI - Fidelity of Thermococcus litoralis DNA polymerase (Vent) in PCR determined by denaturing gradient gel electrophoresis. AB - DNA synthesis fidelities of two thermostable DNA polymerases, Thermus aquaticus (Taq) and Thermococcus litoralis (Tli, also known as Vent), and a non thermostable enzyme, a modified T7 DNA polymerase (Sequenase), were determined by analyzing polymerase chain reaction (PCR) products using denaturing gradient gel electrophoresis (DGGE). The error rates were 4.4, 8.9, and 2.4 x 10(-5) errors/bp for modified T7, Taq, and Tli polymerase, respectively. Reducing the nucleotide triphosphate concentration for Tli polymerase during PCR did not alter the fidelity. The ability of DGGE to detect a mutant present at several percent in a wild type population is related to the polymerase fidelity. To examine the sensitivity of mutant detection, human genomic DNA containing a 1% fraction of a known base pair substitution mutant was PCR-amplified with the three enzymes using primers that flank the mutant sequence. The PCR products were analyzed by DGGE. The signal from the mutant present at 1% was visible in the samples amplified with modified T7 and Tli polymerase, but the higher error rate of Taq polymerase did not permit visualization of the signal in DNA amplified with Taq polymerase. PMID- 1870974 TI - Interaction of ribo- and deoxyriboanalogs of yeast tRNA(Phe) anticodon arm with programmed small ribosomal subunits of Escherichia coli and rabbit liver. AB - A synthetic ribooligonucleotide, r(CCAGACUGm-AAGAUCUGG), corresponding to the unmodified yeast tRNA(Phe) anticodon arm is shown to bind to poly(U) programmed small ribosomal subunits of both E. coli and rabbit liver with affinity two order less than that of a natural anticodon arm. Its deoxyriboanalogs d(CCAGACTGAAGATCTGG) and d(CCAGA)r(CUGm-AAGA)d(TCTGG), are used to study the influence of sugar-phosphate modification on the interaction of tRNA with programmed small ribosomal subunits. The deoxyribooligonucleotide is shown to adopt a hairpin structure. Nevertheless, as well as oligonucleotide with deoxyriboses in stem region, it is not able to bind to 30S or 40S ribosomal subunits in the presence of ribo-(poly(U] or deoxyribo-(poly (dT) template. The deoxyribooligonucleotide also has no inhibitory effect on tRNA(Phe) binding to 30S ribosomes at 10-fold excess over tRNA. Neomycin does not influence binding of tRNA anticodon arm analogs used. Complete tRNA molecule and natural modifications of anticodon arm are considered to stabilize the arm structure needed for its interaction with a programmed ribosome. PMID- 1870975 TI - Site-specific intercalation at the triplex-duplex junction induces a conformational change which is detectable by hypersensitivity to diethylpyrocarbonate. AB - Using site-specific intercalation directed by intermolecular triplex formation, the conformation of an intercalation site in DNA was examined by footprinting with the purine-specific (A much greater than G) reagent diethylpyrocarbonate. Site specific intercalation was achieved by covalently linking an intercalator to the 5' end of a homopyrimidine oligodeoxynucleotide, which bound to a homopurinehomopyrimidine stretch in a recombinant plasmid via intermolecular triplex formation. This directs intercalation to a single site in 3kb of DNA at the 5' triplex-duplex junction. Footprinting with diethylpyrocarbonate and dimethylsulphate revealed strong protection from modification of adenine residues within the triple-helix in concordance with their Hoogsteen pairing with the third strand, and a strong hypersensitivity to diethylpyrocarbonate at the first adenine of the duplex. This result indicates that intercalation at this site induces a conformational change at the 5' triplex-duplex junction. Furthermore, the same diethlypyrocarbonate hypersensitivity was observed with an unmodified triple-strand forming oligonucleotide and a range of intercalating molecules present in solution. Thus the 5' triplex-duplex junction is a strong binding site for some intercalating molecules and the junction undergoes a conformational change which is sensitive to diethylpyrocarbonate upon insertion of the planar aromatic chromophore. This conformational change can be used to direct a single strand cut in duplex DNA to a defined site. PMID- 1870976 TI - A nuclear factor binds to the metal regulatory elements of the mouse gene encoding metallothionein-I. AB - The ability of vertebrate metallothionein (MT) genes to be induced by heavy metals is controlled by metal regulatory elements (MREs) present in the promoter in multiple, non-identical copies. The binding specificity of the mouse L-cell nuclear factor(s) that interact with the element MREd of the mouse MT-I gene was analyzed by in vitro footprinting, protein blotting, and UV cross-linking assays. In vitro footprinting analyses revealed that synthetic oligodeoxynucleotides (oligomers) corresponding to the metal regulatory elements MREa, MREb, MREc, MREd and MREe of the mouse MT-I gene, as well as the MRE4 of the human MT-IIA gene and the MREa of the trout MT-B gene, all competed for the nuclear protein species binding to the MREd region of the mouse MT-I gene, the MREe oligomer being the weakest competitor. In addition, protein blotting experiments revealed that a nuclear protein of 108 kDa, termed metal element protein-1 (MEP-1), which specifically binds with high affinity to mouse MREd, binds with different affinities to the other mouse MRE elements, mimicking their relative transcriptional strength in vivo: MREd greater than or equal to MREa = MREc greater than MREb greater than MREe greater than MREf. Similarly, human MRE4 and trout MREa bind to MEP-1. A protein similar in size to MEP-1 was also detected in HeLa-cell nuclear extracts. In UV cross-linking experiments the major protein species, complexed with mouse MREd oligomers, migrated on a denaturating gel with an apparent Mr of 115,000 and was detected using each of the mouse MRE oligomers tested. These results show that a mouse nuclear factor can bind to multiple MREs in mouse, trout, and human MT genes. PMID- 1870977 TI - Purification of BsuE methyltransferase and its application in genome mapping. AB - We have used a combination of BsuE methyltransferase (M-BsuE) and NotI restriction enzyme to cut genomic DNA at a subset of NotI sites. The usefulness of this system is shown in a re-examination of the restriction map of the human MHC. Combinations of methylases and restriction enzymes can be used to generate cuts at different frequencies in genomic DNA, such that they generate ends complementary to NotI ends, and can be used in conjunction with NotI linking clones in chromosome jumping experiments. These enzyme combinations have the potential to produce cutting sites in genomic DNA spaced at intervals favorable for extensive mapping, fragment enrichment, and cloning efforts. PMID- 1870979 TI - Chemical ligation of DNA: the first non-enzymatic assembly of a biologically active gene. AB - An artificial gene comprising 183 base pairs has been assembled by template directed condensation of 35- to 53-membered oligodeoxyribo nucleotides with cyanogen bromide as a condensing agent. The reaction is complete within several minutes at 0 degrees C in buffer. The resulting mini-gene was cloned and expressed in vivo and in vitro. We have also found that the polymerase inhibition technique (toe-printing) is a good way to ascertain that translation initiation complexes form in the case of single-stranded DNAs as well. Thus, along with the fully chemical assembly of synthetic genes, a rapid and sufficiently reliable method for determining their ribosome-binding properties was developed. PMID- 1870978 TI - Assessment of inhomogeneities in an E. coli physical map. AB - A statistical method based on r-fragments, sums of distances between (r + 1) consecutive restriction enzyme sites, is introduced for detecting nonrandomness in the distribution or too markers in sequence data. The technique is applicable whenever large numbers of markers are available and will detect clumping, excessive dispersion or too much evenness of spacing of the markers. It is particularly adapted to varying the scale on which inhomogeneities can be detected, from nearest neighbor interactions to more distant interactions. The r fragment procedure is applied primarily to the Kohara et al. (1) physical map of E. coli. Other applications to DAM methylation sites in E. coli and NotI sites in human chromosome 21 are presented. Restriction sites for the eight enzymes used in (1) appear to be randomly distributed, although at widely differing densities. These conclusions are substantially in agreement with the analysis of Churchill et al. (3). Extreme variability in the density of the eight restriction enzyme sites cannot be explained by variability in mono-, di- or trinucleotide frequencies. PMID- 1870980 TI - Detection of triple-helix related structures adopted by poly(dG)-poly(dC) sequences in supercoiled plasmid DNA. AB - Negative superhelical strain induces the poly(dG)-poly(dC) sequence to adopt two totally different types of triple-helices, either a dG.dG.dC triplex in the presence of Mg(+)+ at both neutral and acidic pHs or a protonated dC+.dG.dC triplex in the absence of Mg(+)+ ions at acidic pH (1). To examine whether there are still other types of non-B DNA structures formed by the same sequence, we constructed supercoiled plasmid DNAs harboring varying lengths of the poly(dG) tract, and the structures adopted by each supercoiled plasmid DNA were studied with a chemical probe, chloroacetaldehyde. The potential of a poly(dG)-poly(dC) sequence to adopt non-B DNA structures depends critically on the length of the tract. Furthermore, in the presence of Mg(+)+ and at a mildly acidic pH, in addition to the expected dG.dG.dC triplex detected for the poly(dG) tracts of 14 to 30 base pairs (bp), new structures were also detected for the tracts longer than 35 bp. The structure formed by a poly(dG) tract of 45 bp revealed chemical reaction patterns consistent with a dG.dG.dC triplex and protonated dC+.dG.dC triple-helices fused together. This structure lacks single-stranded stretches typical of intramolecular triplexes. PMID- 1870982 TI - Simplified mammalian DNA isolation procedure. PMID- 1870981 TI - A full-length cDNA encoding a mitochondrial DNA-specific single-stranded DNA binding protein from Xenopus laevis. PMID- 1870983 TI - Slide PCR: DNA amplification from cell samples on microscopic glass slides. PMID- 1870984 TI - Drosophila AP3, a presumptive DNA repair protein, is homologous to human ribosomal associated protein P0. PMID- 1870985 TI - Codon utilisation in the pathogenic yeast, Candida albicans. PMID- 1870986 TI - A novel approach for establishing common or random integration loci for retroviral genomes. PMID- 1870987 TI - PCR amplification of mRNA directly from a crude cell lysate prepared by thermophilic protease digestion. PMID- 1870988 TI - Isolation of intact nuclei from hematopoietic cell types. PMID- 1870990 TI - A common polymorphism in the human arylsulfatase B (ARSB) gene at 5q13-q14. PMID- 1870989 TI - G to A polymorphism in exon 45 of the COL1A1 gene. PMID- 1870991 TI - Dinucleotide insertion/deletion polymorphism in intron 50 of the COL2A1 gene. PMID- 1870992 TI - Tetranucleotide repeat polymorphism at the human coagulation factor XIII A subunit gene (F13A1). PMID- 1870993 TI - Trinucleotide repeat polymorphism at the human met-tRNA-i gene 1 (TRMI). PMID- 1870994 TI - Trinucleotide repeat polymorphism at the human transcription factor IID gene. PMID- 1870995 TI - Dinucleotide repeat polymorphism at the D11S534 locus. PMID- 1870996 TI - Dinucleotide repeat polymorphism at the D14S45 locus. PMID- 1870997 TI - An insertion deletion polymorphism associated with C-FES. PMID- 1870998 TI - Detection of a length polymorphism for human GIP gene by polymerase chain reaction. PMID- 1870999 TI - Polymorphism in exon 4a of the human GLUT4/ muscle-fat facilitative glucose transporter gene detected by SSCP. PMID- 1871000 TI - A polymorphism in exon 2 of the human LDL-receptor gene (LDLR). PMID- 1871001 TI - A to G polymorphism in ELN gene. PMID- 1871002 TI - PCR detection of five restriction site dimorphisms at the type I collagen loci COL1A1 and COL1A2. PMID- 1871004 TI - The utility of fractional wash-out slope values following intravenous 133Xe. AB - The regional clearance of 133Xe from the lungs after intravenous administration as well as following rebreathing was assessed in 7 normals and 18 patients with various lung disorders. Each lung was divided into three zones as upper, middle and lower. Regional ventilation (V) and regional perfusion (P) were determined using the area under the first peak at the beginning of the ventilation study and the area under the peak after intravenous administration, respectively. Slopes were calculated using the first exponential of the wash-out curve. Absolute slope values of the wash-out curves after perfusion (Pwo) and ventilation (Vwo) were expressed as a percentage of the total for each lung. Correlation coefficients between V and Vwo, V and Pwo, P and Pwo were .695, .584 and .882 in normals and .610, .461 and .685 in patients, respectively. It is concluded that Pwo is influenced by both perfusion and ventilation; it may reflect the fractional contribution to the gas exchange and can be used in the prediction of residual lung function after lung resection. PMID- 1871005 TI - [Hepatic hydrothorax without ascites]. AB - A case of hepatic hydrothorax without clinical ascites is reported. The diagnosis was confirmed by intraperitoneal injection of 99mTc-tin colloid: scintigraphic images taken between 5 min and 18 h p.i. demonstrated a one-way transdiaphragmatic flow into the pleural cavity. The therapy consisted of diuretic treatment, pleural drainage and chemical pleurodesis, and resulted in prompt clinical improvement. PMID- 1871003 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1871006 TI - [The effect of hyper- and hypothyroidism on the energy metabolism of skeletal muscles--a study using 31P-magnetic resonance spectroscopy]. AB - 31P magnetic resonance spectroscopy allows non-invasive evaluation of phosphorus metabolism in man. The purpose of the present study was to assess the influence of hyper- and hypothyroidism on the metabolism of resting human skeletal muscle. The present data show that quantitative measurement of phosphate metabolism by NMR is possible as also demonstrated by other studies. Using a quantitative evaluation method with an external standard, significant differences in the levels of phosphocreatine, adenosine triphosphate, and phosphodiesters were found. In hypothyroid patients a TSH-dependent increase in phosphodiesters and a decrease in adenosine triphosphate and phosphocreatine was observed. In hyperthyroidism a similar decrease in adenosine triphosphate but a considerably higher decrease in phosphocreatine occurred. In the light of the results of other studies of muscle metabolism, these changes appear to be non-specific so that further studies are required to assess the clinical value of such measurements. PMID- 1871007 TI - [Tumor scintigraphy using 123I-labeled estradiol in breast cancer--receptor scintigraphy]. AB - The estrogen receptor (ER) status is an important factor for prognosis and endocrine therapy of breast cancer. Therefore 16-alpha-123I-iodoestradiol-17-beta (123I-E2) as a receptor-specific radiopharmacon was used for scintigraphic tumor detection in 62 patients suspected of breast cancer. The studies were performed as a multicenter trial (5 university hospitals) to validate the method and to overcome methodical problems. A fast tracer elimination from the blood pool into the liver was seen, followed by biliary excretion allowing early imaging of the thorax due to low background activity but resulting in difficult imaging conditions of the abdomen. In 42 patients (30 carcinomas, 12 benign lesions) the overall sensitivity was 66% (ER status cut-off: 10 fmol/mg). Some patients with breast cancer showed focal or diffuse uptake in the area of primary lymph drainage (parasternal, axillary) without any clinical correlation, demanding follow-up investigations. There was only one false-positive result in a receptor negative primary carcinoma; thus, the non-invasive determination of the ER status seems to be feasible. The sensitivity of 123I-E2 in the detection of primary breast cancer or metastases and recurrences is low compared to mammography and other methods; therefore, 123I-E2 scintigraphy cannot be used as a screening method. Differentiation of malignant and benign tissue is even more difficult as both may have a positive ER status, for example in mastopathy. Nevertheless, 123I E2 scintigraphy is an in vivo imaging technique for the detection of breast cancer depending on the ER status and provides information about tumor localisation. It may become a specific method for the non-invasive diagnosis of the ER status and may be helpful in follow-up studies. As a receptor-specific agent 123I-E2 may give answers to questions of tumor heterogeneity and changes of the ER status during therapy. PMID- 1871008 TI - Starting young. PMID- 1871009 TI - A distressing procedure. PMID- 1871010 TI - Safe haven. PMID- 1871011 TI - Bitter medicine. PMID- 1871012 TI - Mental health--born in the USA. PMID- 1871013 TI - Complementary support. PMID- 1871014 TI - Nursing overseas. The land of the maharajas. PMID- 1871015 TI - Arts in action. A colourful, fresh start. PMID- 1871016 TI - A Delphi study on psychiatric nursing. PMID- 1871017 TI - Pain and depression in the population. PMID- 1871018 TI - Nursing education. Issues--a credit to the profession? PMID- 1871019 TI - Nurse education. How to organize a workshop. PMID- 1871020 TI - Continence--training for success. PMID- 1871022 TI - Continence. Marketing forces. PMID- 1871021 TI - Continence. Nurse, heal thyself. PMID- 1871023 TI - Incontinence. Comment--setting the sights. PMID- 1871024 TI - "Nintendonitis". PMID- 1871025 TI - Alternatives to rationing health care. PMID- 1871026 TI - Influence of bone staple design on interfragmentary compression. AB - Staple fixation, most commonly thought of as static, has been studied with regard to effecting dynamic compression. Features of staple design that relate to the creation of interfragmentary compression have been analyzed, and a simple manipulative technique to effect compression is illustrated. Compressive forces of bone fixation staples were measured using pressure-sensitive film. Thirteen staple designs were tested in a wood-block model and in cadaveric bone. Staples with legs splayed outward produced higher compressive forces than standard staple designs. Internal beveling of the staple leg tips also produced high compressive forces, while external beveling produced distraction. Staples with legs tapered over their entire length produced compression, but caused splitting in the wood block model. Our results show that outward splaying of the staple legs is a simple method to increase compression in any staple design. PMID- 1871027 TI - Clinical experience with automated percutaneous discectomy: the Nucleotome system. AB - The Nucleotome system was used to treat contained herniated nucleus pulposus of the lumbar spine over a 2-year period. The results were categorized as successful or unsuccessful according to patient perception and anticipated result. The overall success rate was 79%; 93% in private pay and 65% in workers' compensation. The causes of failure were three free fragments not identified in the preoperative scanning technique and 10 cases with significant back pain failing to respond to percutaneous techniques. Overall, percutaneous lumbar discectomy is believed to be an acceptable treatment technique for those patients with contained herniated nucleus pulposus. PMID- 1871028 TI - L plate fixation for osteotomies. AB - It is generally acknowledged that stable fixation of osteotomies offers certain benefits, including maintenance of predictable alignment, while permitting rapid mobilization and rehabilitation. A variety of implants are available which require technical proficiency and familiarity by the surgeon for successful implantation. The ability to customize implants before or during surgery allows the surgeon critical control in a variety of situations. An L plate, which is a pre-bent dynamic compression plate (DCP), applied as a tension band with interfragmentary screws serves this purpose well. PMID- 1871029 TI - Proximal femoral focal deficiency: evaluation and management. AB - Proximal femoral focal deficiency is a rare congenital anomaly characterized by limb malrotation, deficiency of the iliofemoral articulation, and limb length discrepancy. Advances in radiology, such as computed tomography and magnetic resonance imaging, have enhanced the assessment of pelvic-femoral instability prior to ossification of the femoral capital epiphysis. The histopathology of the fetal proximal femoral growth plate has been described, which has increased our knowledge about the etiology of the proximal femoral malformation. Data are now available regarding the long-term functional status of patients with severe acetabular dysplasia (Aitken Class C or Class D deformity) following nonoperative management of the hip. A review of the current knowledge regarding proximal femoral focal deficiency is presented to assist the orthopedic surgeon in evaluation and management. PMID- 1871030 TI - Compartment syndrome of the biceps brachii compartment following rupture of the long head of the biceps. PMID- 1871031 TI - Anterior interosseous nerve syndrome associated with forearm band treatment of lateral epicondylitis. PMID- 1871032 TI - Bony gamekeeper's thumb in a skeletally immature girl. PMID- 1871033 TI - Variation in applied force during insertion of cemented femoral prostheses. AB - Information is presented on forces applied to cemented prostheses during insertion. An instrumented femoral pusher was used to collect information during simulated operations on cadavers while using a laboratory test rig and during live surgery. Surgeons using flanged or collared prostheses tend to apply more force than those using collarless prostheses. There is a tendency for abrupt changes in applied force to occur when: 1) clearing cement; 2) easing hand discomfort; and 3) testing cement consistency. Tests showed that an overall impression of the force applied could be obtained from a laboratory simulation, but that clearing cement and testing cement were not modelled by this method. We discuss the implications of our observations in terms of prosthesis fixation and training of staff. PMID- 1871034 TI - Health care rationing: a quality of life issue. PMID- 1871035 TI - Radiologic case study. Sacral insufficiency fracture. PMID- 1871036 TI - Validation of bioanalytical methods. AB - Validation of bioanalytical methods used to generate data for pharmacokinetic and bioavailability studies is approached by a variety of techniques and is subject to many different methods of interpretation. This Review puts the various techniques into perspective and discusses pitfalls which may occur in interpretation of validation data. Recovery studies, standardization techniques, and selectivity/specificity are discussed with regard to the intrinsic value of various techniques that are used in validation. Models used for analytical calibration curves are explained in terms of their validity and limitations, along with a presentation of the most common ways to validate the model. Analytical sensitivity and detection limits are presented and discussed with regard to the usefulness of the various definitions. Appropriate means of testing precision and accuracy, the most important factors in assessing method quality, are presented. Stability and ruggedness testing are discussed along with a presentation of ways to assess data acceptability on a daily run basis. PMID- 1871037 TI - The effects of formulation variables on the stability of freeze-dried human growth hormone. AB - Formulation often has a dramatic effect on degradation of proteins during the freeze-drying process as well as impacting on the "shelf-life" stability of the freeze-dried product. This research presents the results of a formulation optimization study of the "in-process" and shelf-life stability of freeze-dried human growth hormone (hGH). Chemical decomposition via methionine oxidation and deamidation of asparagine residues as well as irreversible aggregation were characterized by HPLC assay methodology. In-process degradation and stability of low moisture freeze-dried solids were studied at 25 and 40 degrees C in a nominal nitrogen headspace (approximately 0.5% O2). Formulation variables included pH, level of salts, and the nature of the lyoprotectant. Studies of the effect of shear on aggregation in solutions indicated that shear comparable to that experienced during filtration does not induce aggregation. Irreversible changes in hGH during the freeze-drying process were minimal, but chemical decomposition via methionine oxidation and asparagine deamidation and aggregation did occur on storage of the freeze-dried solid. Decomposition via methionine oxidation was significant. A combination of mannitol and glycine, where the glycine remains amorphous, provided the greatest protection against decomposition and aggregation. It is postulated that an excipient system that remains at least partially amorphous is necessary for stabilization. However, the observation that dextran 40 formulations showed poor stability toward aggregation demonstrates that an amorphous excipient system is not a sufficient condition for stability. Stability of the solid was optimal when produced from solutions in the pH range, 7-7.5, with severe aggregation being observed at high pH. The level of sodium phosphate buffer affected stability of the solid, although this relationship was complex. Freeze-drying in the presence of NaCl produced severe aggregation and precipitation during the freeze-drying process as well as acceleration of oxidation and/or deamidation. PMID- 1871038 TI - Colon-specific delivery of dexamethasone from a glucoside prodrug in the guinea pig. AB - Dexamethasone-beta-D-glucoside is a potential prodrug for colonic delivery of the antiinflammatory agent, dexamethasone. The ability of this prodrug to deliver dexamethasone selectively to the colon depends not only on its being slowly absorbed from the alimentary canal, but also on its having chemical and enzymatic stability in the stomach and small intestine. Once reaching the large bowel, it should be quantitatively hydrolyzed to release the active agent. The potential of dexamethasone-beta-D-glucoside for colon-specific delivery of dexamethasone is assessed by determining the rates of its hydrolysis down the alimentary canal of the guinea pig, an animal in which an inflammatory bowel disease model has been developed. The hydrolytic activity is examined in tissues and luminal contents of the stomach, proximal and distal segments of the small intestine, cecum, and colon. For the tissues, the greatest hydrolytic activity is in the proximal small intestine, while the stomach, cecum, and colon have only moderate activity. In contrast, the contents of the cecum and colon show greater activity than the contents of the small intestine and stomach. The luminal contents retained beta glucosidase activity even after repeated centrifugation and resuspension in a buffer. The activity was unaffected by homogenization. These observations suggest that hydrolytic activity is associated with enzymes located on the surface of luminal cells. The movement and hydrolysis of dexamethasone-beta-D-glucoside down the gastrointestinal tract of the guinea pig are also examined. About 20 to 30% of an oral dose appears to reach the cecum. Here the prodrug is rapidly hydrolyzed to the active drug. From intravenous administration of the prodrug and drug, it is apparent that dexamethasone-beta-D-glucoside is poorly absorbed in the gastrointestinal tract (bioavailability, less than 1%). There is a ninefold selective advantage for delivery of dexamethasone in cecal tissues in the guinea pig under the conditions of this experiment. Thus, there is a potential for a decrease in the usual dose and a concomitant reduction in the systemic exposure to dexamethasone. Because humans have much less glucosidase activity in the small intestine, even greater site-selective delivery to the cecum and colon is expected. PMID- 1871039 TI - Amine prodrugs which utilize hydroxy amide lactonization. II. A potential esterase-sensitive amide prodrug. AB - In an effort to develop esterase-sensitive pro-prodrugs for amines, an amide derivative of 3-(2'-acetoxy-4',6'-dimethylphenyl)-3,3- dimethylpropionic acid (4 methoxyaniline amide 8) was synthesized and its stability investigated. This esterified hydroxy amide was found under all conditions to degrade via a two-step process initiated by acetyl ester hydrolysis generating the hydroxy amide intermediate 9a. The lactonization of this intermediate 9a in the second step resulted in the formation of 4-methoxyaniline (10) and 4,4,5,7-tetramethyl-3,4 dihydrocoumarin (1a). The pro-prodrug 8 was observed to possess the following half-lives at 37 degrees C under various conditions: 4030 min in phosphate buffer (50 mM, mu = 0.15) fixed to pH 7.4, 11.9 min in the same buffer containing a porcine liver esterase, 53.7 min in plasma, and 475 min in plasma containing diisopropylfluorophosphate. These results suggest that in a biological milieu the ester hydrolysis will occur by the enzymic hydrolysis rather than the chemical hydrolysis and that the enzymic hydrolysis of 8 in plasma is due, in part, to the action of serine-dependent esterases. PMID- 1871040 TI - Molecular structure and dynamics of cis(Z)-and trans(E)-flupenthixol and clopenthixol. AB - The three-dimensional structures and molecular electrostatic potentials of the cis(Z) and trans(E)-isomers of flupenthixol and clopenthixol were examined by computer graphics and molecular mechanical and quantum mechanical calculations, and their internal molecular motions were studied by molecular dynamics simulations in vacuo and in aqueous solution. The simulations demonstrated that both the side chains and the tricyclic ring systems of clopenthixol and flupenthixol are highly flexible. The angle between the two phenyl ring planes varied between 105 and 171 degrees during the simulations in solution. The electrostatic potentials around the 2-substituent were significantly more negative in the trans(E)-isomers than in the cis(Z)-isomers. The stronger negative potentials may weaken electrostatic receptor interactions and, thereby, cause the trans(E)-isomers to be less active than cis(Z)-isomers. Differences both in three-dimensional structure and in electronic structure may cause the difference in pharmacological activity between cis(Z)- and trans(E) thioxanthenes. PMID- 1871041 TI - Effects of viscous hyaluronate-sodium solutions on the nasal absorption of vasopressin and an analogue. AB - The effects of viscous solutions of hyaluronate-sodium of various average molecular weights (MW) on the nasal absorption of vasopressin (AVP) and its analogue, 1-deamino-8-D-arginine vasopressin (1-d-8-DAVP), were examined in rats. Solutions of hyaluronate with MW greater than 3 x 10(5) daltons enhanced the nasal absorption of AVP; solutions of MW 5.5 x 10(4) daltons were not effective. The enhancing effects on the nasal absorption of AVP and 1-d-8-DAVP were dependent on the concentration in the range of 0-1.5% (w/v) hyaluronate (MW 1.4 x 10(6) daltons). The nasal absorption of AVP was increased with this solution at lower pH. Bioavailabilities after nasal administration of AVP and 1-d-8-DAVP in hyaluronate solutions (MW 1.4 x 10(6) and 2 x 10(6) daltons) increased more than 2-and 1.6-fold as compared to nasal administration of AVP and 1-d-8-DAVP in buffer solutions (pH 7.0), respectively. Hyaluronate solution (MW 1.4 x 10(6) daltons) did not affect the ciliary beat frequency of rabbit nasal mucosal membranes in vitro. Therefore, hyaluronate solution may be useful as a vehicle for nasal delivery of AVP and 1-d-8-DAVP. PMID- 1871042 TI - In vitro evaluation of the plasma and blood compatibility of a parenteral formulation for ditekiren, a novel renin inhibitor pseudopeptide. AB - Ditekiren (U-71038; Boc-Pro-Phe-N-MeHis-Leu-psi[CHOHCH2]-Val-Ile (aminomethyl)pyridine ) is a potent renin inhibitor peptide and was formulated for clinical intravenous administration in acidified dextrose. This formulation of ditekiren was evaluated in vitro with human and monkey plasma as to its potential for forming a precipitate either of drug or of plasma proteins. Analysis by centrifugation showed that no drug precipitation occurred in plasma from either species at concentrations 25 times higher than anticipated in clinical studies. Results obtained by turbidimetry indicated that formulated ditekiren did not cause aggregation of human platelets or flocculation of proteins at concentrations approaching the solubility limit of the drug in plasma. Ditekiren or vehicle also caused no detectable lysis of red cells at concentrations representing 10 times the maximum clinical level. Therefore, ditekiren solutions as formulated are judged completely compatible with blood and plasma upon clinical intravenous administration. PMID- 1871043 TI - Inactivation kinetics of enzyme pharmaceuticals in aqueous solution. AB - The kinetics of enzyme inactivation in aqueous solution of neutral pH were studied for alpha-chymotrypsin, bromelain, and kallikrein. Inactivation of alpha chymotrypsin and bromelain followed simple first-order kinetics, and the rate constant obtained conformed to the Arrhenius relationship. Kallikrein, however, presented more complicated kinetics of inactivation, which could be described by a kinetic expression combining a reversible and an irreversible pathway. Nonlinear regression analysis suggested that the rate constants conform reasonably well to the Arrhenius relationship. The results suggest that inactivation of enzymes in aqueous solution can be modeled even if the profile is complicated and that the inactivation rates can be predicted based on the relationship between the parameter estimates and temperature. PMID- 1871045 TI - Effect of polyethylene glycol 400 on the intestinal permeability of carbamazepine in the rabbit. AB - Because of the limited solubility of carbamazepine, aqueous solutions are usually prepared using glycols as cosolvents. This research focuses on the effect of varying the composition of polyethylene glycol 400 (PEG-400) in aqueous solutions in rabbit intestinal permeability of carbamazepine in the duodenojejunum and the ascending colon using an in situ perfusion technique. In both segments the intestinal permeability varied inversely with the percentage of PEG-400, when the concentration of carbamazepine in the perfusing solution was maintained constant. The decreased permeability may be explained by a reduction in the thermodynamic activity of carbamazepine with increased concentrations of PEG-400, as well as by reverse solvent drag because of the hyperosmolarity of the perfusing solutions. PMID- 1871044 TI - Stability of interleukin 1 beta (IL-1 beta) in aqueous solution: analytical methods, kinetics, products, and solution formulation implications. AB - The thermal stability of IL-1 beta in aqueous solution as a function of temperature (5-60 degrees C), pH (2-9), buffer (acetate, citrate, tris, and phosphate), and cyroprotectants (sugars, HSA) was investigated in this study. The analytical methodologies included RP-HPLC, SEC, ELISA, IEF-PAGE, SDS-PAGE, and bioassay. The degradation and inactivation of IL-1 beta at or above 39 degrees C were attributed to autoxidation of the two cysteine residues in the denatured protein, followed by hydrophobic/covalent aggregation and precipitation. At or below 30 degrees C, IEF- and SDS-PAGE results suggest a possible deamidation reaction. The difference in mechanism of degradation precludes the prediction of formulation shelf life from accelerated temperature data. Nonetheless, the good stability observed at 5 degrees C suggests that a solution formulation may be feasible for IL-1 beta. PMID- 1871046 TI - Effects of deoxycholate on the transepithelial transport of sucrose and horseradish peroxidase in filter-grown Madin-Darby canine kidney (MDCK) cells. AB - Madin-Darby canine kidney (MDCK) epithelial cells grown on microporous polycarbonate filters were used as a model system to investigate the mechanisms of enhancement by deoxycholate in the transepithelial transport of horseradish peroxidase (HRP) and 14C-sucrose. Deoxycholate at 0.025% had no effect on the transepithelial electrical resistance (TEER); a fivefold enhancement on the transepithelial transport of HRP, but not on that of 14C-sucrose, was observed. Deoxycholate at 0.05% induced a reversible decrease of TEER; a 2- and 50-fold enhancement on the transepithelial transport of 14C-sucrose and HRP, respectively, was observed. At 0.1%, deoxycholate induced an irreversible decrease in TEER and the epithelial barrier in the cell monolayer was completely eliminated. A 3.3-fold increase in cellular uptake in HRP, but not in 14C sucrose, was also observed in the presence of 0.025% deoxycholate. The increase in cellular uptake was abolished when HRP was conjugated to polylysine. These results suggest that deoxycholate can increase the transepithelial transport by at least two different mechanisms, i.e., a transcellular pathway, possibly due to the enhancement of cellular uptake of selective molecules, and a nonselective paracellular pathway, due to the loosening of tight junctions by deoxycholate at higher concentrations. PMID- 1871047 TI - Cosolvency of dimethyl isosorbide for steroid solubility. AB - Dimethyl isosorbide (DMI), which is currently under investigation for its potential use as a pharmaceutical vehicle and drug permeation enhancer, is a water-miscible liquid with relatively low viscosity. The solubilization behavior of DMI as a cosolvent for nonpolar drugs was characterized via dielectric constant measurements of binary solvent systems containing DMI and either water, propylene glycol (PG), or polyethylene glycol (PEG). Evidence from the dielectric constant profiles and NMR studies suggest that DMI undergoes complexation with water and PG, but not with PEG, through hydrogen bonding interactions. The solvent complexation exhibited a major effect on the solubilities of prednisone, dexamethasone, and prednisolone in the mixed solvent systems. Maximum solubility of each drug was found to occur near a DMI/water or DMI/PG concentration ratio of 1:2. In the DMI-PEG mixed system, while there is no apparent interaction between DMI and PEG molecules, the solubility of prednisone was found to increase with decreasing dielectric constant. PMID- 1871048 TI - Mean residence times and distribution volumes for drugs undergoing linear reversible metabolism and tissue distribution and linear or nonlinear elimination from the central compartments. AB - Equations for the mean residence times in the body (MRT) and in the central compartment (MRTc) are derived for bolus central dosing of a drug and its metabolite which undergo linear tissue distribution and linear reversible metabolism but are eliminated either linearly or nonlinearly (Michaelis-Menten kinetics) from the central compartments. In addition, a new approach to calculate the steady-state volumes of distribution for nonlinear systems (reversible or nonreversible) is proposed based on disposition decomposition analysis. The application of these equations to a dual reversible two-compartment model is illustrated by computer simulations. PMID- 1871049 TI - Suitability of various noninfinity area under the plasma concentration-time curve (AUC) estimates for use in bioequivalence determinations: relationship to AUC from zero to time infinity (AUC0-INF). AB - The influence of random error and elimination rate on estimates of the area under the curve from zero to time infinity (AUCO-INF) was determined in a simulation study using noninfinity measured AUC values (i.e. AUCTM, area to a measured common sampling time, and AUCO-LAST, area to the last measured sampling time). Further, the extent of absorption of generic danazol, baclofen, and oxazepam was determined using measured methods of estimating area under the curve in bioequivalence studies. The noninfinity AUC estimates and their 90% confidence intervals for the difference in product means were compared for each individual drug. Products chosen fulfilled one of the following three criteria: (1) a high "apparent intrasubject variability" and a half-life greater than 8 hr (danazol); (2) a low apparent intrasubject variability and a half-life less than 4 hr (baclofen); and (3) products exhibiting a low apparent intrasubject variability and a half-life greater than 8 hr (oxazepam). For the simulated data, AUCTM performed best when subjects had similar half-lives (i.e., low variability), which results in AUCTM = AUCO-LAST. On the other hand, AUCO-LAST worked best with a high fractional standard deviation (fsd) and a short elimination half-life (i.e., less than 4 hr). The noninfinity 90% confidence intervals for danazol and oxazepam were inconsistent with those observed at AUCO-INF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871050 TI - The preparation and evaluation of a tablet dosage form of cyclosporine in dogs. AB - Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. To improve its variable absorption and low patient acceptability, several oral formulations were prepared and tested in vitro and in vivo in dogs. A tablet formulation prepared by direct compression was then selected for comparison with the commercial oil solution placed into soft gelatin capsules. The study involved a randomized crossover design in six dogs. In order to determine absolute bioavailability and to compensate for any time-dependent changes in clearance, an intravenous tracer dose of 3H-CsA was administered along with each oral test product on each of two occasions. Absolute bioavailability (mean +/- SD) was 46.0 +/- 11.1 and 45.4 +/- 9.9% for the capsules and tablets, respectively. Cmax, tmax, and mean absorption time were not significantly different between the two products. No differences were observed in the pharmacokinetics of the intravenously administered CsA in the two experiments, which were separated by 8-13 days. We conclude that the proposed tablet formulation for CsA is equivalent in dogs to the commercial dosage form placed into soft gelatin capsules. PMID- 1871051 TI - High-performance liquid chromatographic (HPLC) determination of lobenzarit in plasma and its application to a bioavailability study in beagle dogs. AB - A method for the quantitative determination of lobenzarit (2-[(2 carboxyphenyl)amino]-4-chlorobenzoic acid) in dog plasma by high-performance liquid chromatography with UV detection (308 nm) is described. Plasma samples (200 microliters) were treated with acetonitrile and centrifuged, and the clear supernatant injected onto a reversed-phase phenyl column. The method achieved a limit of quantitation of 0.5 micrograms/ml in plasma, and the response was linear to 100 micrograms/ml. Comparing a solution and a tablet formulation given to beagle dogs, the assay demonstrated that the solution formulation was slightly more bioavailable and yielded a more variable absorption rate. The elimination of lobenzarit from plasma followed a biexponential time course, with an apparent terminal disposition half-life of between 5.8 and 10.7 hr. PMID- 1871052 TI - Synthesis of poly(hydroxypropylglutamine-prazosin carbamate) and release studies. AB - Prazosin, an antihypertensive drug with postsynaptic alpha 1-adrenergic blocking activity, has been coupled to poly-N5-(3-hydroxypropyl-L-glutamine) (PHPG) via a carbamate linkage. PHPG was activated by p-nitrophenyl chloroformate and then reacted with prazosin to form p(HPG-prazosin carbamate) conjugate. Drug loading was 23.9% (w/w). Activated polymer and conjugates were characterized by infrared spectroscopy and differential scanning calorimetry. In vitro studies proceeded in pH 7.4 isotonic phosphate-buffered saline solution. Prazosin was released at a rate of 0.92 mg/day/100 mg conjugate from p(HPG-prazosin carbamate) particles. In vivo studies were performed with New Zealand White rabbits. P(HPG-prazosin carbamate) conjugate particles (100 mg) were suspended in 2 ml saline and injected subcutaneously into both flanks of rabbits. P(HPG-prazosin carbamate) conjugates, following an initial burst, demonstrated a nearly constant plasma prazosin concentration profile above 2 ng/ml, which was maintained for 10 days. PMID- 1871053 TI - "On-off" thermocontrol of solute transport. I. Temperature dependence of swelling of N-isopropylacrylamide networks modified with hydrophobic components in water. AB - The swelling in water, as a function of temperature, of two series of N isopropylacrylamide (NIPAAm) polymer networks was studied. In the first series, n butylmethacrylate (BMA) was copolymerized with NIPAAm, and in the second, polytetramethylene ether glycol (PTMEG) was incorporated into NIPAAm network as a chemically independent interpenetrating network. With increasing BMA content in the poly(NIPAAm-co-BMA) network, the gel collapse point was lowered and the gels deswelled in a more gradual manner with increasing temperature. In the interpenetrating polymer networks (IPN) system, the gel collapse point was not significantly changed by the amount of incorporated PTMEG. In DSC thermograms of swollen samples, the shape and onset temperature of the endothermic peak corresponded to the gel deswelling behavior and gel collapse point. The temperature dependence of equilibrium swelling in water was shown to be a function of the gel composition in both network series. The synthesized networks formed a dense surface layer as the temperature increased past the gel collapse point. This dense layer retarded water efflux and thereby resulted in water pockets at the membrane surface. PMID- 1871054 TI - In vitro binding of lorazepam and lorazepam glucuronide to cholestyramine, colestipol, and activated charcoal. PMID- 1871055 TI - Determination of the relative formation and elimination clearance of two major carbamazepine metabolites in humans: a comparison between traditional and pooled sample analysis. PMID- 1871056 TI - Drug metabolism and laboratory anesthetic protocols in the rat: examination of antipyrine pharmacokinetics. PMID- 1871057 TI - Rapid high-performance liquid chromatographic analysis and stability study of hydrocortisone 17-butyrate in cream preparations. PMID- 1871058 TI - Binding of drugs in milk: the role of casein in milk protein binding--comments on the paper by Stebler and Guentert. PMID- 1871059 TI - [Restless children. An exercise in epistemic confusion]. AB - Drawing on systemic thinking (i.e. constructivist systems theory) the paper reviews grossly the assumptions underlying childhood's restlessness ("hyperactivity") both as a distinct nosological entity and as foundation for different treatments. The phenomenon is considered, in accordance with contemporary ideas, as an interactional one. Two case examples serve as a starting point for gathering basic elements which, if put together, allow to understand this phenomenon without falling into the extremes of a mainly medical or a socionormative approach. This permits to make use of the systemic view in a manner that enables the therapist to adopt an attitude of respectful acceptance and understanding towards his/her small clients and their relatives. PMID- 1871060 TI - [Obsessive phenomena in schizophrenic adolescents]. AB - Adolescent schizophrenics show obsessive-compulsive symptoms as often as adult patients. Obsessive-compulsive symptoms occur generally both in premorbid and post-acute states, whereas they are rarely observed in acute states. A particular preference of any schizophrenic subgroup doesn't seem to exist. Obsessive compulsive phenomena are not the same as coping-techniques or (pseudo)-neurotic defense mechanisms, and don't allow a prediction of a distinct outcome. The relationship between schizophrenia and obsessive-compulsive symptoms is variable, and doesn't follow a set pattern. PMID- 1871061 TI - [Systemic concepts in residential placement: considerations for pedagogics, counseling and organization]. AB - The paper starts from an analysis of typical problems in residential child care, which can be identified on different system levels (family, family and residential child care unit, family and larger systems, child care as a profession). More recent systems concepts (such as autopoiesis, role of the observer, "fitting", limits of planning in human systems) are used to develop suggestions for everyday practice of residential child care--from intake to dismissal, from crisis intervention to family education, from job satisfaction to management issues. PMID- 1871062 TI - [Art therapy--an additional possibility in group psychotherapy with adolescents]. AB - Following a discussion of fundamentals of psychoanalytically oriented art therapy, clinical examples are shown to illustrate its practical application within the field of adolescent group psychotherapy. The mutually stimulating and complementing possibilities of expression within the creative process, the art works themselves and the verbal interaction offer a concrete, yet very flexible opportunity for dealing with group activity, transference, individual conflicts and difficulties within the developmental tasks of adolescence. PMID- 1871063 TI - [Re-integration of children into the biological (partial) family]. AB - The article deals with some aspects of a study about reintegration of children from Austrian SOS Children's Villages into their original families. The knowledge that children actually not always return to their original families is of outstanding importance. In the meantime, very often the family has substantially changed because family members joined or left the family. Therefore the term 'reintegration into the original family' reflects the situation insufficiently. Ignoring these changes, many times lead to difficulties within family life. PMID- 1871064 TI - Treating the partially edentulous with the Branemark system. PMID- 1871065 TI - Mission critical. PMID- 1871066 TI - NHS plus--a formula for survival. PMID- 1871067 TI - The perils of 'paradise'. PMID- 1871068 TI - Should you buy the total solution? PMID- 1871069 TI - A high quality amalgam. PMID- 1871070 TI - Corticotrophin-releasing hormone production by the placenta and fetal membranes. AB - Maturation of the fetal hypothalamic-pituitary-axis may be an important factor in the stimulation of the onset of parturition. Recent studies have found that corticotrophin-releasing hormone (CRH), the hypothalamic component of this axis is also present in the placenta and the fetal membranes. We review the evidence demonstrating that glucocorticoids stimulate the production of CRH by these tissues towards term, and this is manifest by increases in CRH concentrations in maternal and fetal plasma and in placental extracts, and by increased abundance of CRH mRNA in the placenta. We discuss how CRH secretion by the placenta and fetal membranes is controlled. We hypothesize that CRH may be an important signal in initiating of the onset and maintenance of term labour and may also be a factor in the etiology of premature labour, through stimulation of the fetal HPA axis, and through paracrine/autocrine interactions within the placenta, fetal membranes and decidua. PMID- 1871071 TI - Villous composition and membrane thickness in the human placenta at term: a stereological study using unbiased estimators and optimal fixation techniques. AB - The aim of this study was to obtain unbiased estimates of in vivo villous composition and membrane thickness in the human placenta at term. By taking biopsies of the placenta 1 min after separation during caesarean section, and at regular intervals thereafter, it was possible to extrapolate back to the time zero values. It was estimated that at term intermediate and terminal villi are composed of 25.3 per cent trophoblast, 36.2 per cent stromal core and 37.1 per cent fetal capillaries. The villous membrane, defined as the outer surface of the syncytiotrophoblast (excluding the microvilli) to the inner surface of the capillary endothelium, was estimated to have an arithmetic mean thickness of 4.53 microns and a harmonic mean thickness of 3.65 microns. Villous composition and membrane thickness were found to change rapidly after delivery, despite the umbilical cord remaining clamped, and these changes were believed to be predominantly due to leakage of fetal blood or plasma from sites of damage to the villous tree caused at the time of delivery. These estimates do not, and indeed cannot, take into account the fact that the villi sampled have been removed from their uterine environment, and thus from the influences of the maternal and fetal blood pressures. However, they are free from methodological errors that have detracted from previous studies, and thus allow the morphometric diffusing capacity of the placenta at term to be calculated more accurately. They also provide baseline data against which measurements obtained from pathological pregnancies can be compared. PMID- 1871072 TI - The activities of thiol proteases in the rat visceral yolk sac increase during late gestation. AB - While the rat YVS has been shown to possess an active lysosomal proteolytic system, there are no published reports on the identity of these proteases nor on their changes in activity during the latter half of gestation. We have used specific synthetic substrates to show that cathepsins B, L and H are present in this organ from days 12.5 to 20.5 of gestation. Cathepsins B and L exhibit a marked increase in activity beginning on day 15.5 of gestation. By days 19.5 20.5, cathepsin B activity is increased tenfold over that observed on day 12.5. The activity of cathepsin L may be elevated on day 12.5, decreases more than half by day 14.5 and then increases fourfold by day 20.5. The activity of cathepsin H does not change throughout this period nor do the cathepsins exhibit marked changes in activity in the placenta during this same period or in the PYS from days 12.5 to 14.5 of gestation. These results indicate a specific increase in VYS cathepsin B and L activities late in gestation. These enzymes may be involved in meeting the nutritional needs of the embryo and/or in the degenerative changes which may occur in the VYS and PYS prior to parturition. Studies on the degradation of rat serum albumin by extracts of day 19.5 VYS indicate that cathepsin L may be the quantitatively most important protease in late gestation. PMID- 1871073 TI - The killing of rat placental cells by rat and mouse granulated metrial gland cells in vitro. AB - Small round cells which migrated from explant cultures of rat metrial gland were identified as granulated metrial gland (GMG) cells. They contained large amounts of glycoprotein and displayed the leucocyte common antigen. Other cells which migrated from the explants were probably derived from the fibroblast-like stromal cells of the metrial gland. The asialo-GM1 antigen was found on rat GMG cells in culture and in cryostat sections of rat metrial gland. The rat GMG cells in culture exhibited locomotion and, when co-cultured with placental cells, made numerous contacts with the placental cells. A small number of these contacts (less than 1 per cent) were followed rapidly by the death of the placental cell. Mouse GMG cells which had migrated from explant cultures of mouse metrial gland were also co-cultured with rat placental cells. The migratory activity of the mouse GMG cells also involved numerous contacts being made with rat placental cells and a small number (less than 1 per cent) of these contacts were cytotoxic for the rat placental cells. The observations support previous suggestions that GMG cells are a type of killer cell. The cytotoxic activity of rat and mouse GMG cells against co-cultured rat placental cells is discussed in relation to the nature of the target molecule involved. PMID- 1871074 TI - Classics revisited: the Yale embryo. 1938. PMID- 1871075 TI - Effects of chorionic GNRH on intrauterine tissues and pregnancy. PMID- 1871076 TI - Relationships among black families' cardiovascular disease risk factors. AB - BACKGROUND: As participants in the District of Columbia Studies of Children's Activity and Nutrition (D.C. SCAN), 262 black mothers and two of each mother's children (3-4 and 8-10 years of age) were measured in their homes for selected cardiovascular disease risk factors: serum total cholesterol, systolic and diastolic blood pressures, height and weight for body mass index, fitness (sum of pulses), activity, and triceps and subscapular skinfolds. RESULTS: For each measure, mothers in the highest quartile were more likely to have children who were also in the highest quartile, and mothers in the lowest quartile were more likely to have children who were in the lowest quartile. For the physiological measures, (with the exception of systolic blood pressure), correlations tended to be stronger between the siblings than between the younger child and the mother, and older siblings' physiological measures contributed to the prediction of younger siblings' physiological measures after controlling for mothers' physiological measures. Relationships between family cardiovascular disease risk factor history and children's serum total cholesterol, and systolic and diastolic blood pressure levels tended to be gender related; i.e., family cardiovascular disease risk factors on the mother's side were more likely to be related to levels among the female but not the male children and vice versa. When personal characteristics were controlled for, the family's cardiovascular disease history was related more strongly to the younger than to the older sibling's systolic and diastolic blood pressure levels. CONCLUSIONS: Results tend to substantiate the importance of screening and counseling other family members, especially a child of the same gender as the parent with a cardiovascular disease or an elevated risk factor level. PMID- 1871077 TI - Prevalence and correlates of hypertension in a subarctic Indian population. AB - BACKGROUND: In a cross-sectional survey of 704 Cree and Ojibwa Indians ages 20-64 in six northern Canadian communities, blood pressure was measured along with various anthropometric, dietary, biochemical, sociodemographic, and lifestyle data. METHODS: Two readings of systolic (SBP) and diastolic (DBP) pressures were obtained using a mercury sphygmomanometer in accordance with WHO protocol. In analyses where blood pressure (BP) was a continuous variable, the means of the two readings were used. Where "hypertension" as a dichotomous variable was used, a "normal" subject was one with no past history of known physician-treated hypertension and who currently had SBP less than or equal to 140 and DBP less than or equal to 90 mm Hg. All others were classified as "hypertensives." RESULTS: Based on these criteria, the adjusted prevalence of hypertension in the sample was 27%, with an increased frequency among males and those in the older age group. Compared with data from the Canada Health Survey, the mean SBP among the Indians exceeded that of Canadians in the younger age groups but was lower beyond age 45. For DBP, Indians had higher mean levels than Canadians consistently across all age groups and in both sexes. On univariate comparisons, significantly higher BP levels were found among men, the old, those with little education, nondrinkers, the physically inactive, the obese, and the diabetic. Hypertensives also differed from nonhypertensives in terms of total cholesterol, triglycerides, high-density lipoprotein cholesterol/total cholesterol ratio, various indices of obesity and fat patterning, and fasting glucose levels. In a multiple logistic regression model, significant predictors of hypertensive status included male sex, age, body mass index, total cholesterol, unemployed and single marital status, and positive family history of hypertension. PMID- 1871078 TI - Nurse-assisted smoking counseling in medical settings: minimizing demands on physicians. AB - BACKGROUND: In an effort to find more practical smoking intervention models for primary-care settings, three physician-and-nurse team approaches to patient counseling were compared with brief physician advice alone. METHODS: Subjects were 3,161 adult smokers surveyed while waiting to see 1 of 40 primary-care physicians. Physicians delivered a brief stop-smoking prompt to 2,707 (86%) of these smokers and referred them to an on-site smoking counselor (e.g., nurse) who randomly provided a two-page pamphlet (advice-only control) or one of three brief nurse-assisted interventions: (a) self-quit training, (b) recruitment to a group program, or (c) a combination intervention. Smokers usually (87%) agreed to see the counselor. RESULTS: After 3 months, subjects in the three nurse-assisted conditions were more likely to report a serious quit attempt (50% vs 39%, P less than 0.001) than were physician-advice-only subjects. Quit rates at 3 months were also higher (P less than 0.001) in the nurse-assisted self-quit (12.9%), recruitment (14.1%), and combination (13.0%) conditions, compared with those for brief physician advice only (7.6%). CONCLUSION: If long-term efficacy is confirmed, these nurse-assisted counseling approaches will serve as practical smoking intervention models for most medical-care delivery settings. PMID- 1871079 TI - Predictors of smoking among Mexican-Americans: findings from the Hispanic HANES. AB - BACKGROUND: This report presents findings from the Hispanic HANES on patterns and predictors of smoking in the Mexican-American subsample. Data are drawn from men and women ages 20-74 years who were administered the Adult Sample Person Questionnaire (N = 3,464). METHODS: Four smoking variables (current, ever, former, and daily consumption) are analyzed in relation to sociodemographic measures, including gender, age, marital status, employment status, occupational prestige, income, acculturation, co-workers' smoking, and presence of others in the home who smoke. All analyses were conducted separately for young, middle-age, and older age groups and for males and females. Multiple logistic and multiple regression analyses were performed, controlling for sociodemographic factors, to identify predictors of smoking. RESULTS: The most important factors found to be associated with smoking were the presence of other smokers in the immediate social environment (home and workplace) and the degree of acculturation (particularly among women). Associations with age, income, and marital status were inconsistent across age and gender groups. With minor exceptions, education, employment, and occupational prestige were unrelated to smoking. CONCLUSIONS: These findings support interventions on the basis of age categories, differential acculturation, and social influence, but overall the findings are more striking for their similarity to predictors of smoking in the general population than for their differences. PMID- 1871081 TI - Symposium overview. American Health Foundation's 20th Anniversary International Symposium on Causes and Prevention of Cancer. December 11-12, 1989, New York City. PMID- 1871080 TI - Racial differences in affirmation of personal habit change to prevent HIV infection. AB - METHODS: In the context of an epidemiological investigation of AIDS-related knowledge, attitudes, and practices, 2,006 employees of the Tennessee Mental Health and Mental Retardation residential facilities were surveyed to test the hypothesis that blacks have been differentially sensitized to their disproportionate level of HIV vulnerability. RESULTS: We found that blacks were significantly more likely than whites to affirm personal habit changes to prevent HIV infection (P less than 0.00001) and significantly more likely to reject the notion that AIDS is not a threat to rural areas of the United States (P less than 0.00001). CONCLUSION: These data were interpreted to be suggestive evidence that blacks have been effectively sensitized to the disproportionate threat of AIDS to the black community and may represent an increased receptivity of blacks to the adoption of HIV preventive practices. PMID- 1871082 TI - [Epidemiological situation and the objectives regarding the intensification of the control of tuberculosis in the Western Siberia]. AB - Analysis of the epidemiological parameters related to tuberculosis in Western Siberia for the last 30 years is given. Tuberculosis still manifests itself as a social disease. The last decade is marked by a slowing down of morbidity reduction. A continuing decrease of registered morbidity is associated with undetected tuberculosis cases owing to a 10-20% reduction of mass population screening. The problem of the interconnection of human and farm animal tuberculosis is still actual for Western Siberia. Morbidity rate among the farm workers in unfavourable regions amounts to 250 per 100,000. Successful tuberculosis control requires joint efforts of phthisiologists, veterinarians and organs of power. PMID- 1871083 TI - [Risk factors of the development of destructive forms of pulmonary tuberculosis in children]. AB - Data are presented on the follow-up of 120 children between the ages of 3 months and 14 years with different forms of destructive pulmonary tuberculosis. The factors responsible for the origination of destructive tuberculosis include the absence or improper conduction of BCG vaccination, contact with patients sick with active pulmonary tuberculosis at the moment of detection or primary contamination, the absence of systematic and high-quality tuberculosis diagnosis; childhood infectious diseases, pneumonias, bronchitis, untimely diagnosed poorly and well manifested forms of intrathoracic tuberculosis in children of the risk groups. PMID- 1871084 TI - [Effect of unfavorable factors on the development of tuberculosis in children]. AB - Analysis of cases of the active forms of tuberculosis in 87 children has established that the first to be affected are children from the unsuccessful families in whom BCG vaccination was either absent or was ineffective. Children from the unsuccessful families aged to 1 year get sick more often. The disease in them runs a more acute course and has manifested clinico-roentgenological symptoms. In half the cases a tuberculosis process acquires a complicated course. PMID- 1871085 TI - [Significance of various factors in the evaluation of tuberculin allergy in children in the early period of primary tuberculosis]. AB - The influence of some factors of ante-, peri- and postnatal periods of life on the intensity of tuberculin allergy in 198 children of pre- and primary school age with a conversion of tuberculin reactions was studied. As a result, 13 indicators out of 52 appeared to be associated with the intensity of tuberculin allergy. This makes it possible to predict the intensity of tuberculin allergy well in advance before the early period of primary tuberculous infection. Keeping a record of the above unfavourable factors in one's case history helps to take differential preventive measures among the contact children. PMID- 1871086 TI - [Clinical course of infiltrative tuberculosis in adolescents]. AB - The course of infiltrative tuberculosis making up 53.2% in the pattern of clinical forms was investigated in 64 adolescents. Infiltrative tuberculosis morbidity among the girls is 3 times higher. The main detection method is represented by a planned roentgenofluorographic examination, since in the region in question infiltrative tuberculosis tends to have limited symptoms in 56.2% of the adolescents, including 30.5% of them even with disseminated process. In 60.9% of the cases, infiltrative tuberculosis is observed to have a decomposition phase which is 4.5 times more frequently traced in patients living in contact with a bacillary ++carrier . In 8% of the patients, infiltrative tuberculosis was complicated by hemoptysis. Infiltrative tuberculosis in 32.8% of the adolescents manifests itself in a pulmonary form of primary tuberculosis. Due to a complex treatment hemodynamic indices are normalized by the end of the first month in addition to the removal of the intoxication signs by the third month. Cavity closure was achieved in 71.8% of the patients. Despite the given therapy, transformation into the destructive forms of tuberculosis took place. PMID- 1871087 TI - [Status of the bronchi in adolescents and young patients with tuberculosis of the respiratory organs]. AB - A comparative analysis is presented of the results of bronchoscopy carried out in 1976-1980 in 406 adolescents and young subjects with different forms of pulmonary tuberculosis and in 115 patients of the same age groups who were examined in 1987 1989. The last decade was marked by the incidence decrease of tuberculosis of bronchi in patients with tuberculosis of respiratory organs from 27.8 to 17.4% and by more benign course. At the same time, the incidence of nonspecific endobronchitis significantly increased (by 3 times). Among the causes of development and growth of the incidence of nonspecific endobronchitis in pulmonary tuberculosis patients the main role is assigned to the deterioration of ecological situation, occupational factors and bad habits. It is considered that nonspecific endobronchitis is not the consequence of pulmonary tuberculosis but are independent diseases having a negative influence on the course of pulmonary tuberculosis. PMID- 1871088 TI - [Tuberculous meningitis in children]. AB - Tuberculous meningitis in children is a rare disease and develops in the absence of the current complex of measures aimed at tuberculosis prophylaxis. In 62.7% of children the disease had a gradual course beginning with a prodromal period with infectious-toxic symptoms being predominant over meningeal and encephalitic ones. Basal localization of the process with cranial nerves involvement was diagnosed in 59% of patients. In 31.8% of children the disease took the course of diffuse meningoencephalitis, 9% has signs of leptomeningitis combined with thromboarteritis of the middle cerebral artery. In 63% of patients the course of meningitis proceeded as a progressive undetected and untreated tuberculosis. Five years later 18% of children died and 9% had nervous system affection. PMID- 1871089 TI - [Combined use of tuberculin and hydrocortisone in the complex treatment of pulmonary tuberculosis]. AB - The paper deals with the results of treatment of 50 active pulmonary tuberculosis patients who at the early terms were given tuberculin in combination with hydrocortisone phonophoresis locally applied on the lesion. The method effectiveness rises in closure of destruction cavities. Tuberculin has an immunomodulatory action and stimulates antibody formation. PMID- 1871090 TI - [Therapeutic possibilities of inhalation of rifampicin with dimexide in phthisiopulmonology]. AB - The efficacy of treatment with rifampicin-dimexide++ aerosols of 184 pulmonary tuberculosis patients and 18 chronic obstructive bronchitis patients was studied. The character of the residual changes following the main chemotherapeutic course was studied in 98 patients. Dimexide++ was proved to be a good rifampicin solvent and synergist enhancing its bacteriostatic action. Rifampicin used in a dose of 150-300 mg in 3-4 ml of dimexide++ in aerosols for 1-2 months promotes bacillary excretion cessation and healing of destruction cavities and allows for a reduction of its toxic action on liver parenchyma. Rifampicin--dimexide++ aerosols contribute to more complete tuberculosis cure and reduce the residual pulmonary and bronchial changes. Rifampicin with dimexide++ can be successfully used for treating chronic bronchitis both as an independent disease and concurrent disease in pulmonary tuberculosis. PMID- 1871091 TI - [Early operations in pulmonary tuberculosis]. AB - Since 1987, 205 patients have undergone early surgical interventions for tuberculomas, and infiltrative and cavernous pulmonary tuberculosis. Comparative analysis of the group of patients treated by conservative and surgical methods in the agreed-upon terms (200 cases) revealed that the clinical efficacy of their management was equal. Nevertheless, the period of sick leave of those early operated appeared to be, on average, 91 days shorter than of those receiving conservative treatment. This in turn made it possible to achieve higher economic efficiency at 2873 roubles per early operated patient. PMID- 1871092 TI - [A differential method of pharmacological prevention of tuberculosis in children in a sanatorium]. PMID- 1871093 TI - [Tuberculosis in adolescents with nonspecific pathology of the respiratory organs]. PMID- 1871094 TI - [Pre-formed therapeutic physical factors in the clinical management of genital tuberculosis]. PMID- 1871095 TI - [Diagnosis of granulomatous lung diseases]. AB - The accumulated experience and the literature data allow for the separation of a group of granulomatous pulmonary diseases among pulmonary diseases of different etiology. Etiologically heterogeneous granulomatous diseases are united by the general signs: granuloma development, immunologic disturbances mainly within the cellular system and mediators as well as systemic vascular affection in the form of vasculitis. In our opinion, granulomatous diseases include disseminated tuberculosis, sarcoidosis of respiratory organs, exogenic and idiopathic fibrous alveolitis, Wegener's granulomatosis, histiocytosis X, primary hemosiderosis, Goodpasture's syndrome and some other rare diseases. Granulomatous diseases are diagnosed on the basis of the ++clinico-roentgenologic findings with an obligatory cytological and histological study of the bioptic specimen; immunologic diseases are diagnosed proceeding from the study of the immunologic status and detection of specific antibodies; of great significance for the diagnosis of pulmonary granuloma caused by infectious pathogens are microbiologic studies which provide for the detection of microorganisms and fungi. Study of the clinicoroentgenologic and laboratory data made it possible to distinguish a number of features typical for each disease and to unite them into diagnostic symptom complexes. Despite the different course of granulomatous pulmonary diseases they may end in recovery and granuloma resolution, development of lung fibrosis in a chronic course and in certain diseases in lung tissue destruction with cavity formation (tuberculosis, Wegener's granulomatosis). A fatal outcome may also ensue due to an acute or chronic course of the diseases. PMID- 1871096 TI - [The blood serum systems in patients with tuberculosis]. AB - Phenotypes of haptoglobin (Hp), group-specific proteins (Gc), transferrins and ceruloplasmin were studied by means of polyacrylamide gel disk electrophoresis of serum proteins in 411 tuberculosis patients and 283 apparently healthy individuals living in the North-West and Extreme North. Regardless of their ethnic affiliation, tuberculosis patients tend to accumulate Hp 2-2, Gc 1-1 carriers and Hp 2-2 + Gc 1-1 combinations. The persons with the above types of individual proteins usually have a serious clinical picture of the disease and lower activity of the immune T-system, as confirmed by different methods of multidimensional statistical analysis. Hp 2-2, Gc 1-1 carriers and Hp 2-2 and Gc 1-1 combinations among the Extreme North's healthy aboriginal population are more widespread than among the healthy inhabitants of the North-West. PMID- 1871097 TI - [Effectiveness of tocopherol and anti-hypoxic agents in liver damage caused by antitubercular agents]. AB - Two-week administration of isoniazid, rifampicin (50 mg/kg and pyrazinamide (1,5 g/kg) to white rats brings about liver affection characterized by a higher activity of alanine and aspartate aminotransferases, lipid peroxidation activation and bile production inhibition. With the liver affected by antituberculous drugs, protective action is provided by acetate tocopherol an antioxidant, and piracetam riboxin and pyriditol, antihypoxic agents. PMID- 1871098 TI - [Changes in plasma levels of corticosterone, testosterone and estradiol and their receptors in the lung cytosol in experimental fibrosing process in the lungs]. AB - The content of blood plasma corticosterone, testosterone and estradiol, and receptors to corticosteroids, androgens and estrogens in pulmonary cytosol of normal male rats and those with fibrosing process in the lungs were experimentally studied by means of radioimmunoassay. With pulmonary fibrosis, a decrease in the concentration of blood plasma corticosterone and testosterone, and lower content of their pulmonary cytosol receptors to corticosteroids, androgens and estrogens are observed. As testosterone propionate was administered in the course of this experiment, there was a normalization of blood plasma corticosterone levels and those of the pulmonary cytosol receptors to androgens. The content of blood plasma testosterone and the pulmonary cytosol receptors to corticosteroids and estrogens was partially normalized. However, it was significantly different from the indices in the control group. PMID- 1871099 TI - [Current state and trends in the development of differential diagnosis of disseminated processes and spherical formations in the lungs based on scientific analysis of documented information flow]. PMID- 1871100 TI - [Propaganda regarding prevention of lung cancer among the groups of patients treated at the anti-tuberculosis clinics]. PMID- 1871101 TI - [Lung cancer in chronic tuberculosis]. PMID- 1871102 TI - [History of tuberculosis control in the pre-Revolutionary Russia-- activities of F.M. Blumental in the organization of health education]. PMID- 1871103 TI - [Complex methods of examination in the diagnosis of disseminated processes in the respiratory organs]. AB - The efficiency of complex methods of examination, including that of the new special ones, for the diagnosis of disseminated processes in the lungs has been studied in 300 patients between the ages of 20 and 76 years. The following methods were used: microbiological (including a new nutritive medium for mycobacteria activation), immuno-enzymatic (detection of specific antigens), immuno-morphologic with determination of antigen determinants of tuberculosis mycobacteria and their L-forms with the help of specific antisera, cytologic, biochemical (the content of phospholipids and their fractions in the bronchoalveolar washing and blood plasma cortisol/insulin ratio), ++tracheo bronchoscopic and surgical methods. A possibility of the verification of the clinical diagnosis of various diseases was established with the help of each method being used. Surgical intervention (thoracoscopy with lung biopsy and open lung biopsy) which confirm the diagnosis in 96.4% of cases proved to be the most informative diagnostic method. PMID- 1871104 TI - The leucine zipper symmetrically positions the adjacent basic regions for specific DNA binding. AB - The bZIP structural motif present in several eukaryotic transcription factors is defined by the leucine zipper, a coiled-coil dimerization interface, and an adjacent basic region that directly interacts with DNA. To examine the functional importance of the highly conserved spacing between the leucine zipper and the basic region, we have analyzed the DNA-binding ability of yeast GCN4 proteins containing amino acid insertions between these two subdomains. Proteins containing a surprisingly wide variety of seven-amino acid insertions, but none containing two-, four-, or six-amino acid insertions, are functional. However, heterodimers between wild-type GCN4 and functional derivatives containing seven amino acid insertions are unable to bind DNA. These observations provide strong experimental support for several aspects of the scissors grip and induced fork models for DNA-binding by bZIP proteins. Specifically, they demonstrate that continuous alpha-helices symmetrically diverging from the leucine zipper correctly position the two basic regions for specific binding to abutting DNA half-sites. In addition, the results indicate that GCN4 homodimers are primarily responsible for transcriptional activation in yeast cells. PMID- 1871105 TI - Molecular cloning and expression of a human heat shock factor, HSF1. AB - Human cells respond to heat stress by inducing the binding of a preexisting transcriptional activator (heat shock factor, HSF) to DNA. We have isolated recombinant DNA clones for a human HSF (HSF1) by screening cDNA libraries with a human cDNA fragment. The human HSF1 probe was produced by the PCR with primers deduced from conserved amino acids in the Drosophila and yeast HSF sequences. The human HSF1 mRNA is constitutively expressed in HeLa cells under nonshock conditions and encodes a protein with four conserved leucine zipper motifs. Like its counterpart in Drosophila, human HSF1 produced in Escherichia coli in the absence of heat shock is active as a DNA binding transcription factor, suggesting that the intrinsic activity of HSF is under negative control in human cells. Surprisingly, an independently isolated human HSF clone, HSF2, is related to but significantly different from HSF1 [Schuetz, T. J., Gallo, G. J., Sheldon, L., Tempst, P. & Kingston, R. E. (1991) Proc. Natl. Acad. Sci. USA 88, 6911-6915]. PMID- 1871106 TI - Isolation of a cDNA for HSF2: evidence for two heat shock factor genes in humans. AB - The heat shock response is transcriptionally regulated by an evolutionarily conserved protein termed heat shock factor (HSF). We report the purification to homogeneity and the partial peptide sequence of HSF from HeLa cells. The peptide sequence was used to isolate a human cDNA with a predicted open reading frame that has homology to the DNA binding domains of both Saccharomyces cerevisiae and Drosophila HSFs. The cDNA directs the synthesis of a protein that binds to the heat shock element with specificity identical to HeLa HSF and stimulates transcription from a heat shock promoter. The expressed protein cross-reacts with anti-HSF antibodies. Surprisingly, however, this cDNA does not encode all of the peptides obtained from purified HeLa HSF. These peptides are encoded by a distinct human cDNA, HSF1, described by Rabindran et al. [Rabindran, S. K., Giorgi, G., Clos, J. & Wu, C. (1991) Proc. Natl. Acad. Sci. USA 88, 6906-6910.] It therefore appears that there is a human heat shock factor gene family and that at least two separate but related HSF proteins regulate the stress response in humans. PMID- 1871107 TI - Leucine aminopeptidase: bestatin inhibition and a model for enzyme-catalyzed peptide hydrolysis. AB - The three-dimensional structures of native bovine lens leucine aminopeptidase (EC 3.4.11.1) and its complex with bestatin, a slow-binding inhibitor, have been solved and exhaustively refined. The mode of binding of bestatin to leucine aminopeptidase may be similar to that of a tetrahedral intermediate that is thought to form during peptide bond hydrolysis. Bestatin binds in the active site with its alpha-amino group and hydroxyl group coordinated to the zinc ion located in the readily exchangeable divalent cation binding site. Its phenylalanyl side chain is stabilized by van der Waals interactions with Met-270, Thr-359, Gly-362, Ala-451, and Met-454, which appear to form a terminal hydrophobic pocket. The leucyl side chain binds in another hydrophobic cleft lined by Asn-330, Ala-333, and Ile-421. Hydrogen bonds involving active site residues Lys-262, Asp-273, Gly 360, and Leu-362 are responsible for stabilizing the backbone nitrogen and oxygen atoms of bestatin. The mode of bestatin inhibition of leucine aminopeptidase is discussed and correlated with biochemical studies of bestatin analogues. In addition, features of a mechanism of catalysis of peptide hydrolysis by leucine aminopeptidase are discussed. PMID- 1871108 TI - Implications of ribozyme kinetics for targeting the cleavage of specific RNA molecules in vivo: more isn't always better. AB - Kinetic and thermodynamic factors that determine specificity of RNA cleavage by ribozymes are illustrated with examples from recent work with a ribozyme derived from the group I intron of Tetrahymena thermophila pre-rRNA. The conclusions also apply to other ribozymes, to antisense oligonucleotide experiments, and to RNA and DNA cleavage agents that can recognize a single-stranded or double-stranded region of variable length. At first, adding bases to a ribozyme's recognition sequence is expected to increase cleavage of the target RNA relative to cleavage of other RNAs. However, adding more bases ultimately reduces this discrimination, as cleavage occurs essentially every time the target RNA or a mismatched RNA binds the ribozyme. This occurs despite the weaker binding of the mismatched RNA because dissociation becomes too slow (binding is too strong) to allow the ribozyme to "choose" between cleavage of the target RNA and a mismatched RNA. In summary, more (base pairing) isn't always better, because maximal discrimination requires equilibrium binding prior to cleavage. The maximum discrimination that can be obtained is expected to be greater with an A + U-rich recognition sequence than with a G + C-rich recognition sequence. This is because the weaker A.U base pairs (relative to G-C base pairs) allow recognition to be spread over a larger number of bases while preventing binding that is too strong. Finally, creating an A-rich ribozyme rather than a U-rich ribozyme avoids the loss in discrimination expected with U-rich ribozymes from the formation of U.G wobble pairs in addition to the "targeted" Watson-Crick U.A pair. PMID- 1871109 TI - Human type VII collagen: cDNA cloning and chromosomal mapping of the gene. AB - A human keratinocyte cDNA expression library in bacteriophage lambda gt11 was screened with the purified IgG fraction of serum from a patient with epidermolysis bullosa acquisita, which had a high titer of anti-type VII collagen antibodies. Screening of approximately 3 x 10(5) plaques identified 8 positive clones, the largest one (K-131) being approximately 1.9 kilobases in size. Dideoxynucleotide sequencing of K-131 indicated that it consisted of 1875 base pairs and contained an open reading frame coding for a putative N-terminal noncollagenous domain of 439 amino acids and a collagenous C-terminal segment of 186 amino acids. The collagenous domain was characterized by repeating Gly-Xaa Yaa sequences that were interrupted in several positions by insertions or deletions of 1-3 amino acids. The deduced amino acid sequence also revealed a peptide segment that had a high degree of identity with a published type VII collagen protein sequence. Northern hybridization of the K-131 cDNA with human epidermal keratinocyte and skin fibroblast RNA revealed an mRNA of approximately 8.5 kilobases. The fusion protein produced by the K-131 cDNA, when incubated with epidermolysis bullosa acquisita serum, bound to antibodies that reacted in Western blots with type VII collagen. The genomic location of the type VII collagen gene (COL7A1) was determined by chromosomal in situ hybridization with the K-131 cDNA. The results mapped the COL7A1 to the locus 3p21. The cDNA clones characterized in this study will be valuable for understanding the protein structure and gene expression of type VII collagen present in anchoring fibrils and its aberrations in the dystrophic forms of heritable epidermolysis bullosa. PMID- 1871111 TI - Transfer of genetic epilepsy by embryonic brain grafts in the chicken. AB - In the Fayoumi chicken, a spontaneous recessive autosomal mutation (F.Epi) is responsible for high susceptibility to seizures that are especially inducible by intermittent light stimulation. Substitution of defined areas of the encephalic neuroepithelium in normal chicken embryos at 2 days of incubation by their counterparts from homozygous F.Epi embryos generates the epileptic phenotype in the chimeras. It was found that grafting primordia of both prosencephalon and mesencephalon of homozygous F.Epi birds is necessary and sufficient for transfer of the full disease. When grafted alone, the homozygous F.Epi prosencephalon, although showing the typical epileptic interictal electroencephalogram, does not allow the complete epileptic seizures to occur in the hosts. Grafts of mesencephalon and/or rhombencephalon modify neither the behavior nor the electroencephalographic pattern of the recipient chickens. Cooperation of forebrain and midbrain activities is therefore required to yield epileptic seizures in this model. PMID- 1871110 TI - BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. AB - The BCL2 protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death. BCL2 was isolated from the chromosomal breakpoint of follicular B-cell lymphoma. Transgenic mice that overexpress BCL2 display extended survival of resting B cells. In this study we use a monospecific anti human BCL2 antibody to define the distribution of BCL2 protein within organized tissues. BCL2 is restricted within germinal centers to the follicular mantle and to portions of the light zone implicated in the selection and maintenance of plasma cells and memory B cells. BCL2 is present in the surviving T cells in the thymic medulla. All hematopoietic lineages that derive from a renewing stem cell also display BCL2. A limited number of nonlymphoid tissues demonstrate BCL2 and can be grouped as (i) glandular epithelium in which hormones or growth factors regulate hyperplasia and involution, (ii) complex differentiating epithelium such as skin and intestine characterized by long-lived stem cells, and (iii) long lived postmitotic cells such as neurons. Within these tissues that demonstrate apoptotic cell turnover, BCL2 is often topographically restricted to long-lived or proliferating cell zones. BCL2's function as an antidote to apoptosis may confer longevity to progenitor and effector cells in these tissues. PMID- 1871112 TI - Large-scale functional reorganization in adult monkey cortex after peripheral nerve injury. AB - In adult monkeys, peripheral nerve injuries induce dramatic examples of neural plasticity in somatosensory cortex. It has been suggested that a cortical distance limit exists and that the amount of plasticity that is possible after injury is constrained by this limit. We have investigated this possibility by depriving a relatively large expanse of cortex by transecting and ligating both the median and the ulnar nerves to the hand. Electrophysiological recording in cortical areas 3b and 1 in three adult squirrel monkeys no less than 2 months after nerve transection has revealed that cutaneous responsiveness is regained throughout the deprived cortex and that a roughly normal topographic order is reestablished for the reorganized cortex. PMID- 1871113 TI - Chemoselective one-step purification method for peptides synthesized by the solid phase technique. AB - The specific reaction between SH and iodoacetamide groups has been explored as the basis of an affinity-type purification procedure for peptides synthesized by the solid-phase technique. For this affinity-type purification procedure, we synthesized an SH precursor reagent bearing an acid-labile S-protecting group, pMB-SCH2CONHCH2CH2-SO2CH2CH2OCO2pNP (compound I), in which pMB is p-methoxybenzyl and pNP is p-nitrophenyl. Using this reagent, the procedure involves the following sequence of four reactions: (i) attachment of the SH function of compound I to the alpha-amino group of a peptide-resin through a base-labile sulfonylethoxycarbonyl linkage in the final step of solid-phase peptide synthesis, (ii) acid treatment to remove the S-pMB and side-chain-protecting groups employed and cleave the modified peptide from the resin, (iii) immobilization of the derived SH-peptide on an iodoacetamide-resin column, and (iv) base (5% NH4OH) treatment to release the desired peptide from the resin in nearly pure form. To facilitate this purification procedure, unreacted amino groups were acetylated in each step during solid-phase synthesis. The usefulness of this method was demonstrated by the purification of several peptides (18 to approximately 44 amino acids in length) synthesized by the 9 fluorenylmethoxycarbonyl (Fmoc)-based solid-phase technique. The principle of this affinity-type purification procedure may also be applied to the tert butoxycarbonyl (Boc)-based solid-phase technique. PMID- 1871114 TI - Expression of RNase P RNA in Saccharomyces cerevisiae is controlled by an unusual RNA polymerase III promoter. AB - The RNA subunit of Saccharomyces cerevisiae nuclear RNase P is encoded by a single-copy, essential gene, RPR1. The 369-nucleotide mature form of the RNA has an apparent precursor with an 84-nucleotide 5' leader and approximately 33 nucleotides of additional 3' sequence. Analysis of RPR1 transcription in a strain with a temperature-sensitive lesion in RNA polymerase III shows that the gene is transcribed in vivo by RNA polymerase III. Examination of potential promoter regions using both progressive upstream deletions and point mutations indicates that at least two sequences contained within the 5' leader region are essential for expression in vivo, while sequences farther upstream influence efficiency. The required leader elements resemble tRNA gene-like A-box and B-box internal promoters in sequence and spacing. As in the tRNA genes, transcription factor TFIIIC binds to this region in vitro and binding is severely reduced by either A box or B-box point mutations that impair expression in vivo. It thus appears that the yeast RNase P RNA gene has adopted a promoter strategy that places an RNA polymerase III "internal" promoter upstream of the mature structural domain to help drive transcription. PMID- 1871115 TI - Evidence that a downstream pseudoknot is required for translational read-through of the Moloney murine leukemia virus gag stop codon. AB - Approximately 5% of the ribosomes translating the gag gene of murine leukemia viruses read through the UAG terminator and translate the in-frame pol gene to produce the gag-pol fusion polyprotein, the sole source of the pol gene products. We show that a pseudoknot located eight nucleotides 3' of the UAG codon in the Moloney murine leukemia virus is required for read-through. This requirement is markedly different from that known to be involved in other cases of read-through but surprisingly similar to some stimulatory sequences known to promote ribosomal frameshifting. PMID- 1871116 TI - Functional reintroduction of human telomeres into mammalian cells. AB - Telomeric sequences of eukaryotes consist of short tandem repeats organized in arrays of variable length in which the guanine-rich strand runs 5'----3' toward the chromosomal end. The terminal repeats in yeast are the only elements necessary for telomere function in this organism. To test whether mammalian terminal repeats can function after reintroduction into a mammalian cell, a repeat-containing terminal fragment from a human chromosome was electroporated into a hamster-human hybrid cell line. In 6 of 27 independent transformants analyzed, the introduced sequences were found at the ends of chromosomes, based on all available criteria. Terminal restriction-fragment heterogeneity and the survival of these chromosomes demonstrate that these telomeres are functional. Cytogenetic evidence from one of these cell lines suggests that chromosome breakage with healing at the integration site is the mechanism responsible for the terminal location. PMID- 1871117 TI - Two genes encoding 1-aminocyclopropane-1-carboxylate synthase in zucchini (Cucurbita pepo) are clustered and similar but differentially regulated. AB - A 17-kilobase (kb) region of the zucchini (Cucurbita pepo) genome has been sequenced and contains two genes, CP-ACC1A and CP-ACC1B, encoding 1 aminocyclopropane-1-carboxylate synthase (ACC synthase; S-adenosyl-L-methionine methylthioadenosine-lyase, EC 4.4.1.14). The genes are transcribed convergently and are separated by a 5.7-kb intergenic region. Their coding regions are interrupted by four introns located in identical positions. While the DNA identity in their coding regions is 97%, their 5' and 3' flanking regions are highly divergent. Transcription of CP-ACCIA is rapidly induced by wounding in fruit and etiolated hypocotyls and by indoleacetic acid (IAA)/benzyladenine/LiCl only in fruit tissue. Conditions that induce CP-ACC1B expression have not been found. Protein synthesis inhibition derepresses the expression of CP-ACC1A and other unidentified ACC synthase genes, suggesting that they may be under negative control. The amino acid sequences deduced from the nucleotide sequences of the genes are 493 and 494 residues long with 95% identity. The most notable feature of the amino acid sequence is the presence of 11 of the 12 invariant amino acid residues involved in the binding of the substrate and pyridoxal-5'-phosphate in various aminotransferases. We conclude that ACC synthase is encoded by a multigene family of which certain members are differentially induced by auxin in a tissue-specific manner. Furthermore, ACC synthase, a pyridoxal-containing enzyme, may have an evolutionary relationship with the superfamily of aminotransferases. PMID- 1871118 TI - An approach for isolation of mutants defective in 35S ribosomal RNA synthesis in Saccharomyces cerevisiae. AB - We have developed a method to isolate mutants of Saccharomyces cerevisiae that are primarily defective in the transcription of 35S ribosomal RNA (rRNA) genes by RNA polymerase I. The method uses a system in which the 35S rRNA gene is fused to the GAL7 promoter and is transcribed by RNA polymerase II under control of the GAL regulatory system. Chromosomal mutations affecting components specifically involved in synthesis of 35S rRNA by RNA polymerase I can be suppressed by this hybrid gene in the presence of inducer (galactose) but not in its absence. We looked for mutants the growth of which depended on the presence of plasmid expressing the hybrid gene. For this purpose, we used a red/white-colony color assay as the initial screen followed by a test for galactose-dependent growth. We have thus isolated many mutants and identified at least nine genes (RRN1-RRN9) involved in 35S rRNA synthesis, two of which correspond to known RNA polymerase I subunit genes RPA190 and RPA135. PMID- 1871119 TI - Static and statistical bending of DNA evaluated by Monte Carlo simulations. AB - To investigate the influence of thermal fluctuations on DNA curvature the Metropolis procedure at 300 K was applied to B-DNA decamers containing A5.T5 and A4.T4 blocks. Monte Carlo simulations have confirmed the DNA bending anisotropy: B-DNA bends most easily in a groove direction (roll). The A5.T5 block is more rigid than the other sequences; the pyrimidine-purine dimers are found to be the most flexible. For A5TCTCT, A5CTCTC, and A5GAGAG, the average bend angle per decamer is 20-25 degrees in a direction toward the minor groove in the center of the A5.T5 tract, which is consistent with both the "junction" and "wedge AA" models. However, in A5T5, A4T4CG, and T4A4GC, bending is directed into the grooves at the 5' and 3' ends of purine tracts. Thus, directionality of bending caused by An.Tn blocks strongly depends on their neighboring sequences. These calculations demonstrate that the sequence-dependent variation of the minor groove width mimics the observed hydroxyl radical cleavage pattern. To estimate the effect of fluctuations on the overall shape of curved DNA fragments, longer pieces of DNA (up to 200 base pairs) were generated. For sequences with strong curvature (A5X5 and A4T4CG), the static model and Monte Carlo ensemble give similar results but, for moderately and slightly curved sequences (A5T5 or T4A4GC), the static model predicts a much smaller degree of bending than does the statistical representation. Considering fluctuations is important for quantitative interpretation of the gel electrophoresis measurements of DNA curvature, where both the static and statistical bends are operative. PMID- 1871120 TI - Resistance of primary isolates of human immunodeficiency virus type 1 to soluble CD4 is independent of CD4-rgp120 binding affinity. AB - The infection of human cells by laboratory strains of human immunodeficiency virus type 1 (HIV-1) can be blocked readily in vitro by recombinant soluble CD4 and CD4-immunoglobulin hybrid molecules. In contrast, infection by primary isolates of HIV-1 is much less sensitive to blocking in vitro by soluble CD4 based molecules. To investigate the molecular basis for this difference between HIV-1 strains, we isolated the gp120-encoding genes from several CD4-resistant and CD4-sensitive HIV-1 strains and characterized the CD4-binding properties of their recombinant gp120 (rgp120) products. Extensive amino acid sequence variation was found between the gp120 genes of CD4-resistant and CD4-sensitive HIV-1 isolates. However, the CD4-binding affinities of rgp120 from strains with markedly different CD4 sensitivities were essentially the same, and only small differences were observed in the kinetics of CD4 binding. These results suggest that the lower sensitivity of primary HIV-1 isolates to neutralization by CD4 based molecules is not due to lower binding affinity between soluble CD4 and free gp120. PMID- 1871121 TI - Limited functional equivalence of phylogenetic variation in small nuclear RNA: yeast U2 RNA with altered branchpoint complementarity inhibits splicing and produces a dominant lethal phenotype. AB - U2 is a highly conserved small nuclear RNA essential for pre-mRNA splicing in mammals and yeast and for trans-splicing in trypanosomes. To test the function of variant U2 RNA structures from different organisms, we conducted phylogenetic exchanges of U2 domains. Replacing nucleotides 1-120 of yeast U2 with the corresponding region of human U2 generates a U2 RNA that is correctly folded and functions in yeast. In contrast, replacement of the branchpoint interaction region of yeast U2 with the corresponding region from trypanosome is dominant lethal. Using a GAL-U2 promoter fusion, we show that the dominant phenotype can be made conditional and that the accumulation of mutant U2 is followed rapidly by inhibition of nuclear pre-mRNA splicing. The results suggest that U2 small nuclear ribonucleoprotein particles normally participate in stable complexes with a limiting splicing factor prior to formation of U2-intron branchpoint base pairs. PMID- 1871122 TI - Single-unit and 2-deoxyglucose studies of side inhibition in macaque striate cortex. AB - In the course of studies to map spatial frequency tuning of neurons in layers 2 and 3 of macaque striate cortex, we found that a high proportion (70%) of cells in the interblob regions responded poorly to full-field gratings, compared with responses to single bars, edges, or delimited gratings. This was most often due to side inhibition, in which increasing the number of cycles of a grating placed within the cell's receptive field causes progressive inhibition of response. Quantitative receptive-field mappings showed, however, that the inhibition can occur within the region activated by a bar, as well as beyond it. The inhibition appears to be orientation-selective, in that a surround grating was more effective at inhibiting the response to a center grating patch if it was of similar orientation. 2-Deoxyglucose experiments confirmed that side inhibition is very widespread in the interblobs of layers 2 and 3 and suggested that it is reduced or lacking in layers 4A through 6. Since layers 2 and 3 of striate cortex are the major source of cortical projections to area V2 and beyond, the prevalence of side stopping in these laminae has implications for theories of cortical visual function. Side-stopped interblob cells may be acting as "contour pass filters" that filter out redundant information in textured or noisy surfaces, focusing subsequent form processing on contrasts corresponding to object boundaries. PMID- 1871123 TI - Oxidative modification by low levels of HOOH can transform myoglobin to an oxidase. AB - It is generally thought that the oxidative modification of hemoproteins leads to their inactivation. In the current study, however, a transiently activated form of myoglobin was shown to be formed when the prosthetic heme group became covalently bound to the polypeptide during the reaction of myoglobin with low levels of HOOH. In the presence of an enzymatic metmyoglobin reducing system containing diaphorase and methylene blue with excess NADH, this HOOH-altered myoglobin catalyzed NADH oxidation and oxygen consumption; the overall stoichiometry indicated a two-electron reduction of oxygen to HOOH. This reaction was not catalyzed by iron released from heme, as desferrioxamine had no effect on the activity. Stoichiometric amounts of HOOH were sufficient to produce the activated oxidase state of myoglobin, whereas larger amounts of HOOH lead to heme destruction, iron release, and inactivation of the oxidase activity. The alteration of myoglobin to an enzyme that can form toxic oxygen metabolites may have pathological importance, especially in myocardial injury caused by ischemia and reperfusion, where myoglobin is present in large amounts and HOOH is formed. Furthermore, the oxidase form may be involved in the mechanism of destruction of the heme seen with oxidative treatment of myoglobin. PMID- 1871124 TI - Repressor to activator switch by mutations in the first Zn finger of the glucocorticoid receptor: is direct DNA binding necessary? AB - Transfection of HeLa cells with cDNA vectors expressing the wild-type human glucocorticoid receptor (GR) enabled dexamethasone to strongly repress cytokine- and second messenger-induced expression of cotransfected chimeric reporter genes containing transcription regulatory DNA elements from the human interleukin 6 (IL 6) promoter. Deletion of the DNA-binding domain or of the second Zn finger or a point mutation in the Zn catenation site in the second finger blocked the ability of GR to mediate repression of the IL-6 promoter. Unexpectedly, deletion of the first Zn finger, a point mutation in the Zn-catenation site in the first finger, or one in the steroid-specificity domain at the base of the first finger converted GR into a dexamethasone-responsive activator that enhanced basal and interleukin 1-induced IL-6 promoter function. These first-finger mutants of GR also mediated dexamethasone-responsive enhancement of expression of the herpesvirus thymidine kinase-chloramphenicol acetyltransferase (TK-105-CAT and TK 80-CAT) reporter genes but not of the murine mammary tumor virus long terminal repeat-CAT or the c-fos-CAT (pFC700) reporter genes. Wild-type GR was able to specifically bind to DNA fragments containing glucocorticoid response element sequences in both the murine mammary tumor virus and IL-6 promoters, albeit weakly to the latter, in a sequential DNA-binding immunoprecipitation assay. The first-finger mutants of GR, however, were inactive in this assay. Thus, mutations in the first Zn finger unmask unusual promoter-specific activation properties of GR that may not require direct high-affinity binding of the mutant GR to target DNA. PMID- 1871125 TI - Protection of macaques with a simian immunodeficiency virus envelope peptide vaccine based on conserved human immunodeficiency virus type 1 sequences. AB - This report describes the vaccination of rhesus macaques with peptides selected from regions of the simian immunodeficiency virus (SIV) envelope that are hydrophilic, immunoreactive, and highly homologous with corresponding conserved envelope sequences of the human immunodeficiency virus (HIV). The peptides, produced as beta-galactosidase fusion proteins, induced virus-neutralizing and peptide-specific antibodies. After challenge with virulent virus, controls became virus positive and developed gradually rising antibody titers to SIV over 63 weeks. Immunized macaques developed a postchallenge anamnestic response to SIVenv antigens within 3-6 weeks followed by a gradual, fluctuating decline in SIV antibody titers and partial or total suppression of detectable SIV. Virus suppression correlated with prechallenge neutralizing antibody titers. Although the average CD4+ cell count in the blood of immunized macaques remained constant, the control macaques exhibited a progressive decrease developing about week 55 after challenge. The conserved nature of the HIV and SIV peptides and the similar humoral immunoreactivity in the respective hosts suggest that homologous HIV peptides may be important components of a successful immunization strategy. PMID- 1871126 TI - Galactosyl ceramide or a derivative is an essential component of the neural receptor for human immunodeficiency virus type 1 envelope glycoprotein gp120. AB - This report demonstrates that galactosyl ceramide (GalCer) or a molecule derived from it may serve as an alternative receptor for human immunodeficiency virus in the nervous system. Recombinant gp120, an envelope glycoprotein of human immunodeficiency virus type 1, specifically binds to GalCer and its derivatives. This specificity was studied by inhibiting binding of radioiodinated gp120 to GalCer with antibodies to GalCer, antibodies to gp120, and an excess of unlabeled gp120. Binding activity was also removed by absorbing gp120 with liposomes containing GalCer. In addition, studies using natural and semisynthetic lipids indicate that the linkage between galactose and ceramide is essential for binding. The significance of an alternative receptor for human immunodeficiency virus in the nervous system is discussed. PMID- 1871127 TI - The Rex regulatory protein of human T-cell lymphotropic virus type I binds specifically to its target site within the viral RNA. AB - The Rex protein of human T-cell leukemia virus type I (HTLV-I) was expressed in bacteria and partially purified. Rex was shown to bind in vitro specifically to an RNA sequence located in the 3' long terminal repeat of HTLV-I, named Rex responsive element (RXRE). Rex also bound in vitro to the human immunodeficiency virus type 1 (HIV-1) Rev-responsive element (RRE), while purified HIV-1 Rev protein did not bind to the RXRE. The binding results obtained in vitro are therefore in agreement with the nonreciprocal function of Rev and Rex in vivo. Rex binds specifically to both RRE and RXRE and activates expression in both HIV 1 and HTLV-I, while Rev binds to RRE and activates only HIV-1. Binding of Rex to RRE deletion mutants previously shown to lack either the Rev-responsive or the Rex-responsive portion suggested preferential binding of Rex to a distinct target within the RRE. These results demonstrated that Rex, like Rev, acts by binding to a specific RNA target. PMID- 1871128 TI - Identification and purification of a factor that binds to the Mlu I cell cycle box of yeast DNA replication genes. AB - In Saccharomyces cerevisiae, the genes encoding at least 10 enzymes involved in DNA replication are periodically expressed in the late G1 and S phases of the cell cycle. All of these genes have one copy or more of the sequence ACGCGT, which conforms to the recognition site for the Mlu I restriction endonuclease. For the CDC21, CDC9, and POL1 genes, the Mlu I site has been shown to be absolutely required for periodic transcription. Using nuclear extracts fractionated by conventional and oligonucleotide affinity chromatography, we have purified a 17-kDa protein that recognizes the Mlu I motif. Synthetic oligonucleotides containing mutated Mlu I sites do not bind the protein. In contrast, synthetic oligonucleotides derived from the CDC2, CDC6, and CDC21 genes, which are expressed with the same timing as POL1, bind purified protein efficiently. PMID- 1871129 TI - Both alpha-helices along the major histocompatibility complex binding cleft are required for staphylococcal enterotoxin A function. AB - The superantigen staphylococcal enterotoxin A (SEA) requires interaction with class II major histocompatibility complex (MHC) molecules to activate T cells. We have previously used the synthetic peptide approach to establish one side of the hypothetical class II foreign-antigen binding cleft, alpha-helical region 65-85 of the beta chain, as a binding site involved in accessory cell presentation of SEA to T cells. To further characterize the structural basis for MHC-SEA interaction we have examined the role of the alpha-helical regions of the class II alpha and beta chains in SEA function. Using the synthetic peptide approach, we have found that both alpha-helical regions are required for SEA-induced proliferation. Their corresponding peptides directly bound SEA. Although the beta chain peptides were able to inhibit SEA binding to human and mouse cells, the alpha-chain peptides were not. The data suggest that the alpha-helices along both sides of the hypothetical class II MHC molecule binding cleft are required for SEA-induced function, whereas the beta-chain alpha-helix is sufficient for SEA binding. A model of superantigen presentation is proposed wherein the MHC beta chain, possibly region 70-80, interacts with SEA region 1-45, whereas another region of SEA binds region 51-80 of the alpha chain. PMID- 1871130 TI - Inhibition of proteolysis protects hippocampal neurons from ischemia. AB - Intense proteolysis of cytoskeletal proteins occurs in brain within minutes of transient ischemia, possibly because of the activation of calcium-sensitive proteases (calpains). This proteolytic event precedes overt signs of neuronal degeneration, is most pronounced in regions of selective neuronal vulnerability, and could have significant consequences for the integrity of cellular function. The present studies demonstrate that (i) the early phase of enhanced proteolysis is a direct response to hypoxia rather than other actions of ischemia, (ii) it is possible to pharmacologically inhibit the in vivo proteolytic response to ischemia, (iii) inhibition of proteolysis is associated with a marked reduction in the extent of neuronal death, and (iv) protected neurons exhibit normal appearing electrophysiological responses and retain their capacity for expressing long-term potentiation, a form of physiological plasticity thought to be involved in memory function. These observations indicate that calcium-activated proteolysis is an important component of the post-ischemic neurodegenerative response and that targeting this response may be a viable therapeutic strategy for preserving both the structure and function of vulnerable neurons. PMID- 1871131 TI - Nonhuman primate model of alcohol abuse: effects of early experience, personality, and stress on alcohol consumption. AB - Twenty-two 50-month-old rhesus monkeys were provided concurrent free access to an aspartame-sweetened 7% ethanol solution and an aspartame-sweetened vehicle before, during, and after social separation. Subjects had been reared for their first 6 months of life either without access to adults but with constant access to age mates (peer reared), a condition producing reduced exploration and increased fear-related behaviors, or as controls with their mothers; thereafter, all subjects received identical treatment. During home-cage periods, for 1 hr each day, 4 days a week, when the ethanol solution and vehicle were freely available, peer-reared subjects consumed significantly more alcohol than mother reared subjects. When stress was increased via social separation, mother-reared animals increased their alcohol consumption to a level nearly as high as that of peer-reared monkeys. Average individual differences in alcohol consumption were markedly stable over time. In addition, there were strong positive correlations between alcohol consumption and distress behaviors. Biological indices of increased stress, such as plasma cortisol and corticotropin, were higher in peer reared subjects. Within the peer- and mother-reared groups, these indices were positively correlated with alcohol consumption. The results suggest that early rearing experiences that predispose monkeys to increased fear-related behaviors produce excessive alcohol consumption under normal living conditions. Furthermore, a major challenge such as social separation increases alcohol consumption to levels producing intoxication even in monkeys not particularly vulnerable to stress. PMID- 1871132 TI - Organization and stability of a polytopic membrane protein: deletion analysis of the lactose permease of Escherichia coli. AB - The overall topology of polytopic membrane proteins is thought to result from either the oriented insertion of the N-terminal alpha-helical domain followed by passive insertion of subsequent helices or from the function of independent topogenic determinants dispersed throughout the molecules. By using the lactose permease of Escherichia coli, a well-characterized membrane protein with 12 transmembrane domains and the N and C termini on the cytoplasmic surface of the membrane, we have studied the insertion and stability of in-frame deletion mutants. So long as the first N-terminal and the last four C-terminal putative alpha-helical domains are retained, stable polypeptides are inserted into the membrane, even when an odd number of helical domains is deleted. Moreover, even when an odd number of helices is deleted, the C terminus remains on the cytoplasmic surface of the membrane, as judged by lacY-phoA fusion analysis. In addition, permease molecules devoid of even or odd numbers of putative transmembrane helices retain a specific pathway for downhill lactose translocation. The findings imply that relatively short C-terminal domains of the permease contain topological information sufficient for insertion in the native orientation regardless of the orientation of the N terminus. PMID- 1871133 TI - Detection of specific polymerase chain reaction product by utilizing the 5'----3' exonuclease activity of Thermus aquaticus DNA polymerase. AB - The 5'----3' exonuclease activity of the thermostable enzyme Thermus aquaticus DNA polymerase may be employed in a polymerase chain reaction product detection system to generate a specific detectable signal concomitantly with amplification. An oligonucleotide probe, nonextendable at the 3' end, labeled at the 5' end, and designed to hybridize within the target sequence, is introduced into the polymerase chain reaction assay. Annealing of probe to one of the polymerase chain reaction product strands during the course of amplification generates a substrate suitable for exonuclease activity. During amplification, the 5'----3' exonuclease activity of T. aquaticus DNA polymerase degrades the probe into smaller fragments that can be differentiated from undegraded probe. The assay is sensitive and specific and is a significant improvement over more cumbersome detection methods. PMID- 1871134 TI - The human enhancer-binding protein Gata3 binds to several T-cell receptor regulatory elements. AB - The tissue-specific developmental regulation of the alpha, beta, gamma and delta T-cell antigen receptor (TCR) genes is controlled by the corresponding distinct enhancers and their enhancer-binding proteins. To find a common TCR regulatory element, we have studied the ability of the newly described enhancer-binding protein Gata3 to bind to the sequence motif (A/T)GATA(G/A) shared between enhancer elements of all four TCR genes. Gata3 was shown in the chicken to be an enhancer-binding protein containing a zinc-finger domain. We have isolated a full length human Gata3 cDNA and characterized its role in TCR gene regulation. Northern blot analysis showed that the Gata3 mRNA is present in T-cell, but not B cell, macrophage or HeLa cell lines. The in vitro transcribed and translated Gata3 cDNA product bound specifically to the enhancer elements of at least three TCR genes containing the above consensus sequence. This binding specificity was consistent with the in vivo activity of the TCR enhancer-binding element in transient transfection assays. Hence, the Gata3 protein, together with other T cell-specific enhancer-binding proteins, may form the basis of tissue-specific expression of the TCR genes. PMID- 1871135 TI - Human liver glucokinase gene: cloning and sequence determination of two alternatively spliced cDNAs. AB - A human liver glucokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) cDNA was isolated from a liver cDNA library. This cDNA (hLGLK1) appeared to be full length [2548 base pairs (bp) plus additional poly(A) residues], as its size was consistent with a single 2.8-kilobase (kb) glucokinase mRNA on Northern blot analysis of liver poly(A)+ RNA. The cDNA contained an open reading frame of 1392 bp that predicted a protein of 464 amino acids and a molecular mass of 52 kDa; this protein has 97% identity to rat liver glucokinase. Fourteen residues on the amino terminus of the predicted human liver glucokinase, however, differed completely from those of the predicted rat liver enzyme and could be explained by alternative splicing of a 124-bp cassette exon in human cDNA. A second glucokinase cDNA (hLGLK2), missing the 124-bp cassette exon, was isolated by PCR amplification of human liver cDNA. The hLGLK2 cDNA contained an open reading frame of 1398 bp from an ATG codon at position 164, encoding a predicted protein of 466 residues, 98% identical to the rat enzyme, but different from the predicted protein of hLGLK1 cDNA by 16 amino-terminal residues. In contrast, hLGLK1 cDNA contains multiple initiator codons upstream of the predicted initiator codon at position 294 within the cassette exon. Translation of the two mRNAs in vitro by a reticulocyte lysate system resulted in proteins of the expected size (52 kDa) for both mRNAs; yet hLGLK2 mRNA was translated four to six times more efficiently. These results suggested that the alternative splicing of a cassette exon in hLGLK1 resulted in an mRNA with an upstream initiator codon and reduced function. The relative biological activity of the two isoforms of human glucokinase and their possible developmental and/or metabolic regulation remain to be determined. PMID- 1871136 TI - Prevention of human immunodeficiency virus type 1 integrase expression in Escherichia coli by a ribozyme. AB - Ribozymes are potentially very powerful agents for perturbing intracellular gene expression. However, pilot experiments in eukaryotes have met with mixed success. We now report that a ribozyme designed to cleave the integrase gene of the human immunodeficiency virus (HIV), when transcribed from a plasmid in Escherichia coli, led to destruction of integrase RNA and complete blockage of integrase protein synthesis. These results indicate that ribozymes can be used to study intracellular gene expression in bacteria and that the HIV-1 integrase gene may be a useful target for therapeutic ribozymes. PMID- 1871137 TI - Two essential components of the Saccharomyces cerevisiae transcription factor TFIIIB: transcription and DNA-binding properties. AB - RNA polymerase III transcription factor TFIIIB from Saccharomyces cerevisiae contains at least two polypeptides, with apparent masses of 90 and 70 kDa, that were previously identified by photocrosslinking to DNA. It is shown here that TFIIIB can be chromatographically separated into two components, each of which is required for efficient tRNA gene transcription. DNA-protein photocrosslinking experiments show these two components separately contain the 90- and 70-kDa TFIIIB-specific polypeptides. The 70-kDa component forms a heparin-sensitive complex with transcription factor TFIIIC and DNA, stabilizes TFIIIC interaction with the tRNA gene promoter elements, and protects against DNase I digestion in the 3' portion of the upstream DNA sequence that is occupied by TFIIIB. The 90 kDa component of TFIIIB, which only detectably interacts with the TFIIIC-DNA complex when the 70-kDa component is also present, generates the complete DNase I protection pattern of TFIIIB and bestows heparin-insensitivity on the TFIIIB-DNA complex. The resolution of TFIIIB into two functional components further defines the probable steps and interactions involved in the formation of stable transcription complexes. PMID- 1871138 TI - Expression, secretion, and lipid-binding characterization of the N-terminal 17% of apolipoprotein B. AB - The N-terminal 17% of human apolipoprotein B (apoB-17) was expressed in murine C127 cells following transfection with a bovine papilloma virus-based expression vector. A permanent cell line overexpressing the expected 89-kDa protein was selected and characterized. Pulse-chase experiments showed that the depletion of intracellular apoB-17 follows an apparent first-order kinetics with t1/2 = 51 min. Under conditions of continuous labeling, greater than 60% of the total synthesized apoB-17 was secreted in a soluble form, approximately 98% lipid-poor and approximately 2% lipid-bound. Inclusion of 1.2 mM oleate resulted in 5- and 2.5-fold increases in the amount of labeled apoB-17 in the p less than 1.063 g/ml and 1.063 less than p less than 1.21 g/ml fractions, respectively, which was coordinated with increased secretion of radiolabeled core lipids, triacylglycerols, and cholesteryl esters. Thus under conditions in which lipid pools are enriched a greater fraction of apoB-17 may be secreted on lipoprotein like particles. The lipid-poor apoB-17 present in p greater than 1.21 g/ml readily associates with exogenously added dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles to form discoidal particles. Discs formed with DMPC/apoB 17, 7:1 (wt/wt), are 239 +/- 43 A in diameter and 61 +/- 4 A thick and contain approximately 2 molecules of apoB-17 and 2250 molecules of DMPC per disc. Based on volume calculations we conclude that apoB-17 forms an annulus about one bilayer high and 10 A thick surrounding the DMPC disc. Circular dichroic spectra of apoB-17 on DMPC discs showed apoB-17 to contain 39% alpha-helix, 36% beta sheet, 9% beta-turn, and 16% random coil. To be consistent with this model greater than 70% of apoB-17 on DMPC discs must bind to lipid. These data suggest that the N-terminal 17% of apoB-100 can bind lipid and may contribute to some extent to the stabilization of triglyceride-rich lipoproteins. PMID- 1871140 TI - Tension responses to rapid pressure release in glycerinated rabbit muscle fibers. AB - We have previously shown that the isometric tension of a fully calcium-activated skinned rabbit psoas muscle fiber is reversibly depressed by increased hydrostatic pressure. We report here the characterization of tension transients induced by a rapid (less than 1-ms) release of increased pressure at 12 degrees C. The tension transient consists of three clear phases, an initial further decrease of tension in phase with pressure change followed by two phases of tension increase back to the level recorded at ambient pressure. The mean reciprocal relaxation time for phase 2 (1/tau 2) was approximately 17 s-1 and that for phase 3 (1/tau 3) was 3 s-1. The presence of 20 mM inorganic phosphate markedly increased 1/tau 2 to approximately 52 s-1 and decreased 1/tau 3 to approximately 1.7 s-1. These observations are interpreted in terms of a pressure sensitive transition between two attached crossbridge states of low (or zero) and higher force. This is compatible with the pressure-sensitive isomerization of actomyosin previously observed in solution. The results presented allow us to propose a coupling between a specific pressure-sensitive isomerization of purified actomyosin, the phosphate release step of the ATPase pathway, and the force-generating event of the cross-bridge cycle. PMID- 1871139 TI - A homeodomain protein binds to gamma-globin gene regulatory sequences. AB - Developmental regulation of gamma-globin gene expression probably occurs through developmental-stage-specific trans-acting factors able to promote the interaction of enhancer elements located in the far upstream locus control region with regulatory elements in the gamma gene promoters and 3' A gamma enhancer located in close proximity to the genes. We have detected a nuclear protein in K562 and baboon fetal bone marrow nuclear extracts capable of binding to A+T-rich sequences in the locus control region, gamma gene promoter, and 3' A gamma enhancer. SDS/polyacrylamide gel analysis of the purified K562 binding activity revealed a single protein of 87 kDa. A K562 cDNA clone was isolated encoding a beta-galactosidase fusion protein with a DNA binding specificity identical to that of the K562/fetal bone marrow nuclear protein. The cDNA clone encodes a homeodomain homologous to the Drosophila antennapedia protein. PMID- 1871141 TI - Human immunodeficiency virus type 1 regulator of virion expression, rev, forms nucleoprotein filaments after binding to a purine-rich "bubble" located within the rev-responsive region of viral mRNAs. AB - The human immunodeficiency virus type 1 rev protein binds with high affinity (Kd less than 1-3 nM) to a purine-rich "bubble" containing bulged GG and GUA residues on either side of a double-helical RNA stem-loop located toward the 5' end of rev response element RNA. High-affinity rev binding is maintained when the bubble is placed in heterologous stem-loop structures, but rev binding is reduced when either the bulged residues or flanking base pairs in the stem are altered. Rev binding to the purine-rich bubble nucleates assembly of long filamentous ribonucleoprotein structures containing polymers of rev bound to flanking RNA sequences. It is proposed that rev regulates human immunodeficiency virus RNA expression by selectively packaging viral transcripts carrying the rev-response element sequence into rod-like nucleoprotein complexes that block splicing of the packaged mRNAs. PMID- 1871142 TI - Design and synthesis of a specific endothelin 1 antagonist: effects on pulmonary vasoconstriction. AB - The 21-amino acid vasoconstrictor peptide endothelin (Et) contains two disulfide bonds. We investigated the importance of the outer disulfide bond in Et-1 by replacing it with an amide linkage. Bioactivity was assessed in an isolated guinea pig lung preparation (perfused at constant flow with Ringer's solution/0.5% albumin) in which pulmonary artery pressure was monitored. Et-1 produced concentration-dependent pulmonary vasoconstriction at concentrations of 1 x 10(-10) M and higher. [Dpr1, Asp15]Et-1 (where Dpr is diaminopropionic acid), in which the outer disulfide was replaced by an amide bond and the inner disulfide was left intact, showed no agonist activity at 1 x 10(-6) M but 1 x 10( 7) M [Dpr1, Asp15]Et-1 inhibited Et-1-induced pulmonary vasoconstriction: effects of 1 x 10(-10) M 2 x 10(-10) M, and 1 x 10(-9) M Et-1 were inhibited by 98%, 75%, and 65%, respectively. Furthermore, this analog did not alter pulmonary vasoconstriction induced by thrombin, norepinephrine, or, most significantly, Et 3. A monocyclic Et-1 analog with the same sequence but in which the amide bond was not formed showed weak pulmonary vasoconstrictor activity (300-500 times less potent than Et-1) but had no antagonist activity. In addition, both the monocyclic control peptide and [Dpr1, Asp15]Et-1 competed effectively with 125I labeled Et-1 for binding to cultured rat pulmonary artery smooth muscle cells. Thus, an Et-1 structural analog produced by replacement of the outer disulfide bond with an amide linkage displayed potent and specific Et-1 antagonism. PMID- 1871143 TI - Cytoduction in Chlamydomonas reinhardtii. AB - After conjugation between Chlamydomonas gametes of opposite mating type, a transient dikaryon is formed. The two nuclei fuse within 4-6 hr after mating. The young diploid zygote differentiates into dormant zygospore competent to complete meiosis, or more rarely (2-10% of cases) it undergoes mitosis to produce a stable diploid progeny. We here bring genetical, biochemical, and cytological evidence that among the mitotic zygotes, a large proportion of them undergo cytokinesis without fusion of the nuclei-a process that has been termed "cytoduction." By using appropriate genetic markers, haploid cytoductants that possess the nuclear genotype of one parent and the chloroplast marker of the other parent can easily be isolated. Genetical analysis and hybridization experiments moreover show that many haploid cytoductants transmit the chloroplast DNA molecules of both parents and that, as in diploids, these DNA copies occasionally recombine. This process of cytoduction extends the life cycle of Chlamydomonas and provides new tools for its genetic analysis. PMID- 1871145 TI - Molecular cloning, sequence, and tissue distribution of the human ubiquitin activating enzyme E1. PMID- 1871146 TI - The role of colony-stimulating factors in host defenses. PMID- 1871144 TI - Surfactant protein B: lipid interactions of synthetic peptides representing the amino-terminal amphipathic domain. AB - The mechanisms by which pulmonary surfactant protein B (SP-B) affects the surface activity of surfactant lipids are unclear. We have studied the peptide/lipid interactions of the amino-terminal amphipathic domain of SP-B by comparing the secondary conformations and surface activities of a family of synthetic peptides based on the native human SP-B sequence, modified by site-specific amino acid substitutions. Circular dichroism measurements show an alpha-helical structure correlating with the ability of the peptides to interact with lipids and with the surface activity of peptide/lipid dispersions. Amino acid substitutions altering either the charge or the hydrophobicity of the residues lowered the helical content and reduced the association of the aminoterminal segment with lipid dispersions. Surface activity of peptide/lipid mixtures was maximally altered by reversal of charge in synthetic peptides. These observations indicate that electrostatic interactions and hydrophobicity are important factors in determining optimal structure and function of surfactant peptides in lipid dispersions. PMID- 1871147 TI - The embryotoxicity of phenytoin: an update on possible mechanisms. AB - PHT has multiple effects in adult humans and animals, and there is no reason to assume that it will not have multiple effects in embryos and fetuses. Although one of the first associations between anticonvulsant therapy and an adverse development effect in humans was noted in 1964 (104), the mechanism(s) whereby these adverse effects occur has thus far eluded research efforts. In this review, I have focused on three possible mechanisms. Overall, the evidence does not appear to implicate folate deficiency in PHT-induced embryotoxicity. A role for glucocorticoids or interaction between PHT and the glucocorticoid receptor has not been ruled out. However, a significant amount of work remains to be done to examine the involvement of the arachidonic acid cascade in PHT-induced embryotoxicity in vivo. The bulk of the experimental evidence would seem to favor a role for the generation of a reactive intermediate and its subsequent binding to embryonic macromolecules. This metabolite(s) has not been identified. Additionally, the association between covalent binding of metabolites and embryotoxicity remains simply an association; a causal relationship has not been established. Much work remains to be done to determine whether any of these possibilities, some other possibility, or a combination of several mechanisms will explain the adverse development effects of this very important, therapeutically useful anticonvulsant. PMID- 1871148 TI - Turkey and chicken prolactins stimulate the proliferation of rat Nb2 lymphoma cells. AB - The purpose of this investigation was to assess the actions of two avian prolactins (PRL) on rat Nb2 lymphoma cell proliferation. Various turkey and chicken PRL preparations stimulated the proliferation of rat Nb2 cells. The ability of avian PRL preparations to influence the behavior of rat Nb2 lymphoma cells provides a useful method for monitoring the PRL-like actions of native and recombinant avian PRL and suggests a potential role of PRL in modulating the avian immune system. PMID- 1871149 TI - Bile acid accumulation in gastric mucosal cells. AB - Bile acids are one of the components of the gastric contents capable of disrupting the mucosal barrier to diffusion. The mechanism by which bile acids can damage the gastric epithelium is not completely understood. Several studies have emphasized mucosal lipid solubilization by bile acids in the pathogenesis of mucosal injury. Bile acid entry into gastric mucosal cells may be a critical and early step in the genesis of mucosal injury, but this possibility has not yet been investigated. The present study was designed to explore the interaction of bile acids with dispersed gastric mucosal cells isolated from the rabbit and guinea pig stomach. Results showed that both glycocholic and deoxycholic acid rapidly associated with the gastric cells and reached a steady state concentration by 30 min. Glycocholic acid accumulated in the cells to a concentration approximately eight times greater than that in the surrounding medium. The amount of bile acid associated with the cells was greater at an acidic than at a neutral pH, and was a function of the concentration of both the cells and the bile acid. The process did not require cellular energy, was nonsaturable, and was not species specific. Experiments with 86Rb, a cytoplasmic marker, revealed that approximately one half of the cellular glycocholic acid was associated with the cytoplasmic compartment and the rest with the membranes. These findings are consistent with a combination of intracellular entrapment of the bile acids due to intracellular ionization and bile acid binding to cellular membrane components being the mechanisms by which bile acids accumulate in cells. Acid-driven bile acid accumulation may explain how relatively low luminal concentrations of bile acid can be damaging to the gastrointestinal mucosa. PMID- 1871150 TI - Technique for repeated collection of cerebrospinal fluid from cisterna magna of anesthetized strain 13 guinea pigs. AB - To study biochemical changes in cerebrospinal fluid (CSF), we developed a reliable technique for repeated collection of CSF in anesthetized strain 13 guinea pigs. The animal's head was mounted in a stereotaxic instrument with ventral tilt at 30 degrees, and cisternal puncture was made with an L-shaped, 23 gauge needle through the shaved skin. Clear CSF was collected in a 1-ml syringe surrounded by crushed ice. Each collection procedure lasted for 3 min, and three consecutive collections produced about 0.2 ml of CSF. Sampling was repeated at 3 hr intervals. With intravenous saline infusion (10 ml/kg.hr), a total volume of 0.6-1.0 ml of CSF was collected over 6 to 12 hr. Animals maintained a mean blood pressure, heart rate, and minute volume, with few changes during CSF sampling for the entire collection. PMID- 1871151 TI - 3-phenylacetylamino-2,6-piperidinedione inhibition of rat Nb2 lymphoma cell mitogenesis. AB - 3-Phenylacetylamino-2,6-piperidinedione (A10), an amino acid analog, has been reported to possess antineoplastic activity against certain neoplastic tissues. The antimitogenic properties of A10 were studied by determining its effect on prolactin (PRL)- and interleukin 2 (IL-2)-stimulated mitogenic responses in the rat Nb2 lymphoma cell line. The addition of A10 (1-12 mM) to PRL (0.4 ng/ml) stimulated cells inhibited growth in a dose-dependent manner. DNA synthesis patterns studied by thymidine incorporation demonstrated that A10 was significantly inhibitory (25% at 20 hr; 50% at 40 hr, P less than 0.01). IL-2 stimulation of mitogenesis was also sensitive to A10 inhibition. The inhibition of PRL stimulated mitogenesis was reversible when A10 was removed after 24 hr of culture and A10 showed no toxicity in a chromium release assay. These data suggest that A10 effects may be cytostatic, rather than cytotoxic. PMID- 1871152 TI - Comparison of lipolytic and antilipolytic activities of lower vertebrate growth hormones on chicken adipose tissue in vitro. AB - Mammalian and avian growth hormones (GH) (pituitary derived or biosynthetic) exert two effects on chicken adipose tissue explants in vitro. They (i) increase the basal rate of glycerol release a lipolytic effect) and (ii) inhibit glucagon stimulated glycerol release (an antilipolytic effect). The ability of lower vertebrate GH preparations to exert lipolytic and antilipolytic effects was examined and biological activity was compared to differences in amino-acid residue sequences and to predicted structure. Irrespective of species origin (blue shark, sturgeon, bonito, yellow tail, salmon, bullfrog, sea turtle), all lower vertebrate GH preparations showed very weak (less than 5% the potency of bovine GH), if any, lipolytic activity, but retained strong antilipolytic activity. The present data indicate that the structural requirements for lipolytic and antilipolytic activities of GH differ in chicken adipose tissue. Despite the high sequence homology (88%) between chicken and sea turtle GH, the latter preparation did not stimulate lipolysis. It is suggested that Pro132, conserved only in lipolytically active GH species (human, bovine, and chicken), represents a major determinant of lipolytic activity in chicken adipose tissue. The structural determinants for antilipolytic activity may comprise any or all of residues 3, 17, 64, 108, 109, and 152. PMID- 1871153 TI - Characterization of transferrin receptor released by K562 erythroleukemia cells. AB - A soluble form of transferrin receptor has been detected in human serum and has been shown recently to be a truncated form of the intact membrane bound receptor. Mechanisms governing the release of transferrin receptor by cells are poorly understood and could be better defined by tissue culture. The present investigation was undertaken to characterize the transferrin receptor released by K562 erythroleukemic cells. In contrast with maturing sheep reticulocytes, which have been shown to release transferrin receptor in small vesicles termed exosomes, we demonstrated, with a monoclonal enzyme-linked immunoassay, that less than 30% of the transferrin receptor released by K562 cells in log phase growth was in a particulate form. The relative amounts of soluble and particulate receptor released to the supernatant did not change significantly during 48 hr of incubation. Soluble receptor was purified by immunoaffinity chromatography. On polyacrylamide gel electrophoresis, its mobility was the same (85 kDa) as that of the truncated monomeric form recently identified in human serum. Further evidence that serum and soluble receptors released by K562 cells are identical was provided by amino acid sequence analysis, which demonstrated that 16 of the first 19 residues of the N-terminal sequence of soluble K562 receptor are homologous with the serum receptor. The remaining three were not identifiable. K562 cells provide a useful in vitro model for studying the production of membrane-bound and soluble forms of released transferrin receptor. PMID- 1871154 TI - Stimulation of leukocyte lysophospholipase activity by noninfectious agents. AB - Mouse peritoneal leukocyte lysophospholipase (LPL) activity was studied to determine whether or not noninfectious agents cause increased enzyme activity and whether neutrophils have LPL activity. In the first study, mice infected with Ascaris suum, a known inducer of LPL activity, were given intraperitoneal injections of proteose peptone, thioglycolate, bovine albumin, paraffin, glycogen, or A. suum whole worm extract (WWE). Cell populations collected from mice injected with A. suum WWE, proteose peptone, thioglycolate, or bovine albumin contained increased numbers of neutrophils and eosinophils. These cell populations had increased LPL activity when treated, in vitro, with either A. suum WWE, zymosan-activated complement, or with the agent they were induced with. However, the LPL activity of the different cell populations did not respond to all treatments in the same way. In a second study, A. suum-infected or noninfected mice were given intraperitoneal injections of paraffin, thioglycolate, glycogen, or A. suum WWE. Enriched cell populations containing either lymphocytes or macrophages, from infected or noninfected mice, did not have increased LPL activity following in vitro stimulation with A. suum WWE, zymosan-activated complement, or with the agent they were induced with. Enriched neutrophil populations from infected or noninfected mice had increased LPL activity following in vitro treatment with A. suum WWE or zymosan-activated complement. Results demonstrate that the LPL activity of peritoneal leukocytes can be induced by noninfectious agents and that neutrophils have increased LPL activity following in vitro stimulation. PMID- 1871155 TI - Purification from human pregnancy serum of a low molecular weight mitogen similar to placental lactogen and growth hormone. AB - Recently, we isolated from the serum of pregnant women a factor that induced rapid proliferation of a lactogen-dependent rat lymphoma cell line (Nb2). This mitogenic factor is reasonably specific to pregnancy, since it was present in serum samples from second trimester as well as term-pregnant women, but not in those of adult men or cycling females. It is unlikely that this mitogenic activity (referred to as pregnancy mitogen [PM]) is due to contamination by classical lactogens, since acetone fractionation of serum yielded a preparation devoid of placental lactogen and prolactin, as determined by radioimmunoassays. Further purification of acetone precipitates from term-pregnant serum by ion exchange chromatography and gel filtration yielded a mitogenic activity with a relative mol wt of approximately 10,000. PM activity in the NB2 cell bioassay was not affected by the presence of prolactin antiserum. However, its activity was immunoneutralized by coincubation with anti-placental lactogen serum and, to a lesser extent, anti-growth hormone serum. It appears that PM was not generated by our extraction procedure, since gel filtration of whole serum also yielded a bioactive fraction of approximately 10 kDa. PM was further purified to homogeneity by high-performance liquid chromatography. Examination of the preliminary amino acid composition of PM revealed differences from that of a bioactive fragment of growth hormone and a corresponding portion of placental lactogen, suggesting that PM could be either a molecular variant of these hormones or a novel protein. PMID- 1871156 TI - Endocrine characteristics of a miniature condition in Brahman cattle: circulating concentrations of some growth-related hormones. AB - Four miniature Brahman calves born in 1988 and 1989, along with four contemporary sex-matched Brahman control calves, were used in experiments to determine circulating concentrations of insulin-like growth factor I (IGF-I), growth hormone (GH), insulin, triiodothyronine, and thyroxine, and plasma glucose response to insulin challenge. The effect of plane of nutrition on plasma concentrations of IGF-I and insulin was also determined and a clinical screen of blood chemistries was conducted to determine effects of calf type. Plasma IGF-I was six times higher in control calves compared with miniature calves (209.0 vs 35.0 ng/ml; P = 0.001). However, miniature calves had mean plasma GH about six times higher (37.8 vs 6.2 ng/ml; P = 0.004) and had twice as many secretory episodes (9 vs 4.5; P = 0.005) over an 8-hr sampling period. Plasma concentrations of triiodothyronine (2.54 vs 1.80 ng/ml) and thyroxine (88.8 vs 56.2 ng/ml) were higher in control compared with miniature calves (P = 0.001), but concentrations of triiodothyronine and thyroxine in both calf types were within normal ranges. Although miniature calves displayed similar plasma glucose concentrations to controls, hypoglycemic response to insulin challenge tended to be greater in miniature calves. Nutritional regulation of circulating IGF-I appeared to be intact in miniature as well as control calves, as evidenced by a reduction in plasma IGF-I concentration following a decrease in plane of nutrition, and a subsequent increase in plasma IGF-I concentration following realimentation. Serum urea nitrogen was lower (P = 0.02) in control compared with miniature calves. These data describe a miniature condition in Brahman cattle that is manifested by apparently normal proportioned growth but small stature, and that is associated most notably with abnormally low circulating concentrations of IGF-I in the presence of paradoxically high circulating concentrations of GH. This condition appears to be similar to Laron dwarfism in humans, in which the low IGF-I is caused by an abnormality in the GH receptor. PMID- 1871157 TI - A comparison of plasma prolactin levels in young female Long-Evans and Holtzman rats as measured by Nb2 lymphoma bioassay and radioimmunoassay. AB - This study was conducted to determine the plasma levels of prolactin in prepubertal and young, postpubertal, proestrus rats of mammary tumor-susceptible (Sprague-Dawley) and tumor-resistant (Long-Evans) strains using a sensitive bioassay-Nb2 lymphoma cell replication. Prepubertal Long-Evans rats had significantly higher levels of prolactin than did Holtzman Sprague-Dawley rats of the same age. Likewise, Long-Evans rats secreted significantly more prolactin into the blood on the afternoon and evening of proestrus than did Holtzman rats. Finally, ovariectomized Long-Evans rats released more prolactin into the blood at 1 day, but not at 8 or 15 days, of treatment with diethylstilbestrol. Prolactin levels determined by conventional radioimmunoassay and by bioassay were similar except on the afternoon of proestrus, when, in both strains of rats, the bioassay to radioimmunoassay ratio increased significantly above 1.0 during the late evening. In addition, the ratio was significantly less than 1.0 in the early and late afternoon in the Holtzman rats, but not Long-Evans rats. These data indicate that a strain of rats that is resistant to experimentally induced mammary cancer has higher prolactin levels in the blood than does a strain that is susceptible to mammary cancer at a time when mammary gland growth is rapid. Furthermore, there are times during the proestrus prolactin surge when the bioassay yielded higher and lower values of prolactin than radioimmunoassay of the same samples, suggesting functional heterogeneity of prolactin that may impact on mammary gland or other target tissue function. PMID- 1871158 TI - Intestinal cadmium permeability in mature and immature rats. AB - To compare the intrinsic permeability properties of the small intestine in adult (average body wt 300 g) and 25- to 27-day-old (average body wt 50 g) male rats, the uptake rates of cycloleucine and of cadmium were measured in intestinal segments isolated in situ with their blood supply intact. Uptake rates were expressed on the basis of that of ethanol, a solute whose absorption depends primarily on the size, rather than the composition, of the available surface area and on the presence of unstirred layers. These layers may be concluded to affect movement of cycloleucine, cadmium, and ethanol to the same extent. The ratio of uptake rates, therefore, provides in arbitrary units a measure of the intrinsic permeability of the luminal surface area to cadmium and to cycloleucine. On this basis, no developmental change in cycloleucine permeability could be detected. In contrast, the rate of cadmium uptake relative to that for ethanol decreased with age by about 50%. Possible mechanisms are discussed for this significant change in the intrinsic cadmium permeability of the jejunum in post-"closure" animals. PMID- 1871160 TI - A computerised assessment for clinical care. An expert system for pressure sore management. AB - Computer technology can be used to provide practical guidance in the clinical setting. This article describes how an expert system was devised to assist nurses in the decision making process required in pressure sore management. PMID- 1871159 TI - Effect of beta agonists on protein turnover in isolated chick skeletal and atrial muscle. AB - Various beta-adrenergic agonists were found to inhibit rates of protein degradation and net protein breakdown in isolated chick extensor digitorum communis (EDC) and atrial muscles. Rates of protein synthesis were not altered by these compounds. The beta-agonist cimaterol inhibited rates of protein degradation in EDC muscles incubated with or without amino acids and insulin. Cimaterol also inhibited the increased proteolysis induced by injury to muscle or by incubating muscles at body temperature (42 degrees C) versus 37 degrees C. Thus, beta-agonists may help promote skeletal muscle accretion in vivo even under conditions of severe negative nitrogen balance by slowing muscle proteolysis. PMID- 1871161 TI - Breaking the barrier. Behavioural management of chronic pain. AB - Psychological and environmental factors can significantly affect chronic pain. A behavioural programme can extend sufferers' capacity for movement and activity, but requires a positive but forceful nursing approach. PMID- 1871162 TI - A structured way to fulfil ambition. How to make rational career plans. AB - All too often, long-term career plans are left to chance. By assessing both personal needs and the wide variety of options open to them, nurses can embark on a structured career plan. PMID- 1871163 TI - Coping with psoriasis. AB - Psoriasis can vary in severity from being a mild nuisance to a debilitating long term condition. Sufferers need practical help to cope with the condition and minimise its effects on their lives. PMID- 1871164 TI - Managing your psoriasis. PMID- 1871165 TI - Cancer self-help groups: a vital support link. PMID- 1871166 TI - Anorexia nervosa--a nursing challenge that can bring results. PMID- 1871167 TI - Motivation can prolong life expectancy. A health education programme to help people give up smoking. AB - Smoking is an acknowledged risk factor for coronary heart disease, but can seem impossible to give up. A health education plan can provide the necessary structure and motivation to help people stop smoking. PMID- 1871168 TI - Managing a budget at ward level. AB - Implementing resource management requires open communication, access to information and the authority to effect change. Once these have been assured, hospitals may develop individual and contrasting systems to meet particular ward needs. PMID- 1871169 TI - A quiet revolution in the public arena. Fulfilling nursing potential in the community. AB - Primary healthcare is undergoing a period of profound change. Community nurses are at the forefront of a campaign to involve people more in their own healthcare and to do this effectively, they need in-depth training to ensure clinical expertise and boost their communication skills. PMID- 1871170 TI - A natural setting for personal advice. Setting up a GP practice family planning clinic. AB - General practices are the most convenient setting for many people to go for family planning advice. With training, practice nurses can become an integral part of the service, offering counselling, support and advice to enable clients to make informed choices about appropriate planning. PMID- 1871171 TI - A screen test worth taking. PMID- 1871172 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 1871173 TI - The biosynthesis of the 3-series prostaglandins in rat uterus after alpha linolenic acid feeding: mass spectroscopy of prostaglandins E and F produced by rat uteri in tissue culture. AB - The abnormal uterine activity associated with dietary n-3 fatty acids may result from competitive inhibition of PG2 production. Uterine synthesis of 2- and 3 series prostaglandins F(PGF) and E(PGE) was studied using mass spectrophotometry in rats fed diets containing predominantly n-3 fatty acid, n-6 fatty acid, or control pelleted diet. Mass spectra of PGF (Me, TMS and Me, TBDMS derivatives) synthesised by uteri of n-3 fed rats were characterised by 8 ions containing the n-3 double bond, and m.i.d. of the 651/653 ions of PGF-Me, TBDMS indicated PGF3 alpha synthesis (44 +/- 8% and 13 +/- 2% of PGF release by uteri incubated + or 5 micrograms/ul calcium ionophore A23187 respectively). In uteri from the control diet group incubated with ionophore, PGF3 alpha ions were detected and PGF 3 alpha represented 9.5 +/- 1.0% of PGF alpha release. Similarly, analysis of PGE from uteri of n-3 fed rats indicated that PGE3 (16 +/- 6% of PGE) was released in the presence of ionophore A23187. Synthesis of 3-series PG by rat uteri was detected after only 3 weeks of n-3 diet. The capacity to synthesise 3-series PG increased at intracellular calcium concentrations which mimicked cell calcium during decidual autolysis at parturition. These experiments suggest that uterine synthesis of 3-series PG is regulated by the specifity of enzymes incorporating fatty acids, rather than by the cyclooxygenase enzyme. PMID- 1871174 TI - Arachidonic acid as a mediator of some of the actions of phorbolmyristate acetate, a tumor promoter and inducer of differentiation. AB - Phorbolmyristate acetate or 12-O-tetradecanyl phorbol 13-acetate (PMA or TPA) stimulates membrane phospholipases (phospholipase C or A2) resulting in the formation of diacylglyceride, free arachidonic acid, and increased amounts of arachidonic acid metabolites. Both PMA and AA are stimulators of the respiratory burst in phagocytic cells, induce inflammation, cause chromosomal aberrations, have anti-viral activity and activate protein kinase C. The initial action of PMA is on the cell membrane and is concentrated largely in the lipid phase of cell membranes. This evidence suggests that the actions of PMA are in large part mediated by AA, released from the cell membrane lipid pool. Thus, it is likely that the ability of PMA to induce terminal differentiation in HL-60 cells and to suppress C-myc mRNA levels are also mediated by AA and/or its products. This may have relevance to the possible role of AA in the regulation of oncogenes and cancer. PMID- 1871175 TI - The effects of evening primrose oil, safflower oil and paraffin on plasma fatty acid levels in humans: choice of an appropriate placebo for clinical studies on primrose oil. AB - In a number of diseases, plasma levels of linoleic acid are normal or elevated while those of gamma-linolenic acid (18:3n-6, GLA) and further metabolites are below normal. Evening primrose oil (EPO), similar to safflower oil (SFO) except that it contains 8-9% of 18:3n-6, has been proposed as a therapeutic agent in these diseases, such as atopic eczema. There is argument as to whether an appropriate placebo for clinical studies on EPO should be an inert material such as paraffin, or a linoleic acid--containing oil such as SFO. We have therefore compared in normal humans the effects on plasma fatty acids of administering EPO, SFO and paraffin for 10 days. Paraffin had no effect on any fatty acid in any fraction. EPO raised the level of 20:3n-6 (dihomo-gamma-linolenic acid, DGLA) the immediate metabolite of GLA but had no significant effect on arachidonic acid. In surprising contrast, SFO raised the levels of linoleic and of arachidonic acids, without raising those of DGLA. This suggests that linoleic acid may be rapidly converted to arachidonic acid by a tightly linked enzyme sequence: GLA, in contrast, may be rapidly converted to DGLA but then only slowly on to arachidonic acid. These results are consistent with recent in vitro observations by others on rat hepatocytes and human fibroblasts. PMID- 1871176 TI - Immunosuppression by seminal plasma from fertile and infertile men: inhibition of natural killer cell function correlates with seminal PG concentration. AB - Human seminal plasma has uniquely high concentrations of PGE and 19-hydroxy PGE but the function of these PGs has not been elucidated. PGs of the E series have been shown to be paracrine and autocrine regulators of the function of immune cells and high levels of PGE have been shown consistently to suppress function in such cells. Human seminal plasma has a potent immunosuppressive effect and evidence is accumulating that this is largely due to PG components. In this study the effects of human seminal plasma on the killing activity of natural killer (NK) cells as judged by 51Cr release from K562 cells have been studied in groups of fertile and infertile men. Although there was no significant difference in the PGE, 19-hydroxy PGE or the NK cell inhibitory activity in the two groups, the inhibition of NK cell activity was closely correlated with the PGE and the 19-OH PGE content of the seminal plasma in the fertile group. This finding is further evidence that the major contribution to the immunosuppressive properties of human semen is provide by the high concentration of PGs of the E series in this fluid. PMID- 1871177 TI - Mechanisms involved in the stimulation by cycloheximide of prostaglandin production in the guinea-pig uterus. AB - Cycloheximide produced a large increase in prostaglandin (PG) E2 output and smaller increases in PGF2 alpha and 6-keto-PGF1 alpha when superfused over the guinea-pig uterus for 20 min. This stimulation of the outputs of these 3 PGs by cycloheximide did not require extracellular calcium. TMB-8 (an intracellular calcium antagonist) had no effect on the stimulation of PGE2 output by cycloheximide, but it completely prevented the stimulation of PGF2 alpha and 6 keto-PGF1 alpha outputs. W-7 (a calmodulin antagonist) had no effect on the stimulation of PGE2 and PGF2 alpha outputs by cycloheximide, but it partially reduced and delayed the stimulation of 6-keto-PGF1 alpha output. Neomycin (a phospholipase C inhibitor) did not prevent the increases in PGE2 and 6-keto-PGF1 alpha outputs produced by cycloheximide. However, neomycin (5 and 10 mM, but not 1 mM) inhibited the small increases in PGF2 alpha caused by cycloheximide. On its own, neomycin produced a dose-dependent, transient increase in 6-keto-PGF1 alpha output without affecting the outputs of PGF2 alpha and PGE2. It is concluded that different mechanisms are involved in the processes by which cycloheximide stimulates the syntheses of PGE2, PGF2 alpha and 6-keto-PGF1 alpha in the guinea pig uterus. PMID- 1871178 TI - Monthly Prostaglandin Bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 1871179 TI - Antiulcerogenic and antiinflammatory actions of fatty acids on the gastrointestinal tract. PMID- 1871180 TI - The effect of dietary n-3 and n-6 fatty acids on tumor necrosis factor-alpha production and leucine aminopeptidase levels in rat peritoneal macrophages. AB - The purpose of this study was to determine the effect of dietary n-3 and n-6 fatty acids on tumor necrosis factor-alpha (TNF-alpha) production and macrophage (MO) activation state. Rats were fed diets containing 12.5% linseed oil (LO) or corn oil (CO) that are high in n-3 and n-6 fatty acids respectively. The LO diet resulted in a significant increase in basal and endotoxin (LPS)-induced levels of TNF-alpha from resident MO cultured in vitro. There was no difference between the diets in LPS-induced TNF-alpha production by complete Freund's adjuvant (CFA) elicited macrophages. Variable responses were also observed between LO and CO MO in response to prostaglandin E2, indomethacin (INDO), and the prostaglandin E receptor antagonist SC-19220. This may indicate differences in signal transducing secondary messengers due to different activation states, receptor expression or ligand binding. Fluorescence due to leucine aminopeptidase (LAP) staining was determined by flow cytometry. Resident LO MO had a 15% increase in LAP fluorescence compared to CO MO. In CFA-elicited MO, the CO MO had a 43% increase in fluorescence compared to LO MO. Resident LO MO increased in LAP fluorescence by 35% to the activated state whereas resident CO MO increased in LAP fluorescence by 93%. The smaller window of activation for the LO MO may explain some of the antiinflammatory properties of dietary n-3 fatty acids. PMID- 1871181 TI - Effects of PGF2 alpha on the EMG of costal and crural parts of the diaphragm of the newborn pig. AB - We investigated the effects of PGF2 alpha on the breathing patterns and electric activity of costal and crural parts of the diaphragm in 9 anesthetized newborn pigs. The change in diaphragmatic tension was evaluated as the change in transdiaphragmatic pressure. Because PGF2 alpha induces bronchoconstriction and an increase in respiratory resistances, the changes induced by prostaglandin were evaluated as differences between bronchoconstriction after PGF2 alpha and resistive load obtained by applying gradual occlusion to the inspiratory line of the breathing circuit. Our results show that PGF2 alpha decreased respiratory frequency with lengthening of expiratory time, while the resistive load increased both respiratory phases. The changes in breathing pattern were associated with different electrical activities of the diaphragm. While resistive load did not significantly change the EMG power spectrum, PGF2 alpha recruited new motor units. Furthermore, resistive load induced synchronization of the inspiratory time discharge of the costal and crural parts of the diaphragm, while after PGF2 alpha infusion there was an early inspiratory discharge of the crural part. PMID- 1871182 TI - Vascular eicosanoid production in experimental hypertensive rats with different mechanisms. AB - This study investigated the release of prostacyclin (PGI2) and thromboxane A2 (TXA2) from the aortic walls of various experimental hypertensive rats, e.g. spontaneously hypertensive rats (SHR), Dahl salt-sensitive (Dahl S) rats, deoxycorticosterone (DOCA)-salt hypertensive rats and renovascular (2-kidney, 1 clip (2K1C) and 1-kidney, 1-clip (1K1C] hypertensive rats. The PGI2 generation was increased significantly in these hypertensive models, irrespective of the hypertensive mechanisms, when they developed established hypertension. Dahl S rats, having an impaired PGI2 production on a low salt diet, restored PGI2 generating capacity to the control level of Dahl salt-resistant rats when they were fed a high salt diet and developed salt-induced hypertension. On the other hand, the TXA2 generation in the vascular walls was enhanced particularly in rat models for genetic hypertension, and this system was unaltered in the models for secondary hypertension, e.g. DOCA-salt and renovascular hypertension. Thus, it is suggested that the elevation of blood pressure is associated with an increase in vascular PGI2 production, and that the increased vascular TXA2 production is a characteristic feature of genetic hypertension. PMID- 1871183 TI - The influence of age on renal prostaglandin synthesis in man. AB - The purpose of our study was to determine influence of age on renal prostaglandin (PG) synthesis in man. Urinary prostaglandins 6-Keto-PGF1 alpha, TxB2, PGE2 and PGF2 alpha were measured in 45 normotensive subjects aged from 20-95 years. Urinary 6-Keto-PGF1 alpha excretion, reflecting mainly renal cortical prostacyclin synthesis, decreased significantly with age, while urinary TxB2 showed the opposite development. The ratio of urinary 6-Keto-PGF1 alpha/TxB2 decreased with age. PGE2 excretion was preserved in old subjects probably because the age-dependent decrease in renal function concerns mainly the cortex and spares the medulla. PGF2 alpha synthesis was least influenced by age. This age dependent decrease in renal prostacyclin synthesis may play a role in the renal alterations of the elderly. PMID- 1871184 TI - Fatty acid and prostaglandin metabolism in children with diabetes mellitus. II. The effect of evening primrose oil supplementation on serum fatty acid and plasma prostaglandin levels. AB - Our previous study demonstrated that levels of dihomo-gamma-linolenic acid (DGLA) and arachidonic acid in serum total lipids decreased in association with increased plasma levels of prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) in patients with insulin-dependent diabetes mellitus. In this study, 11 children with insulin-dependent diabetes mellitus completed a double-blind, placebo controlled study to assess the effect of dietary supplementation with gamma linolenic acid (GLA) on serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. GLA was given as the seed oil from the evening primrose (EPO) and all patients received either EPO capsules (containing 45 mg of GLA and 360 mg of linoleic acid) or indistinguishable placebo capsules for 8 months. Initially patients took 2 capsules daily for 4 months then 4 capsules daily for a further 4 months. All patients were assessed at the start of the study, after 4 months and at the end of the study, by measuring serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. After administration of 4 capsules daily the DGLA levels increased and PGE2 levels decreased significantly (p less than 0.01) in the EPO compared with the placebo group. Neither fatty acid nor PGE2 and PGF2 alpha levels were altered by administration of 2 EPO capsules daily. This suggests that the altered essential fatty acid and PG metabolism in diabetes may be reversed by direct GLA supplementation. PMID- 1871185 TI - Behavioral effects of ethanol inhalation in rats. AB - Behavioral effects of ethanol inhalation were studied on two fixed-ratio (FR) liquid-reinforced schedules and a continuous reinforcement (CRF) schedule intracranial self-stimulation (SS) in rats using the inhalational behavioral chamber designed in our laboratory. In the FR-24 schedule ethanol caused a decrease of reinforcement rate at 161 ppm and higher concentrations. In the FR-50 schedule decreases of the rate were observed at 102 ppm and 203 ppm. In the SS behavior ethanol produced a decrease in the rate of reinforcement at 603 ppm and higher concentrations. In rats of this schedule, blood ethanol concentrations were measured to be 393 micrograms/ml and 545 micrograms/ml after exposure to 600 ppm and 1200 ppm of ethanol respectively. Acute tolerance to ethanol was observed in these experiments, particularly in the FR-24 schedule. Thus ethanol inhalation could produce adequate blood concentrations so as to produce behavioral effects. PMID- 1871186 TI - Behavioral effects of intracerebral administration of luteinizing hormone releasing hormone (LHRH) in rats. AB - The effects of LHRH intracerebrally infused on acquisition of conditioned avoidance responses (CARs) and spontaneous motility were studied in adult male rats. The results were the following: 1) LHRH (1 and 2.5 micrograms/rat) administered through a cannula stereotaxically implanted into the lateral ventricle induced an impairment in the acquisition of CARs along with an increase in global motility, rearing, head shaking and grooming behavior; 2) LHRH 1 microgram/rat injected into the hippocampus or nucleus accumbens induced also an impairment in acquisition which is evident 15 min after treatment. In contrast, intrastriatal injection induced an immediate disruption of this behavior; and 3) there is a good dose-response relationship for intrastriatal LHRH between 7.8 and 62.5 ng/rat. The results suggest that the estriatum could be the locus of the LHRH-induced inhibition of CARs. Then the possibility of an involvement of the dopamine nigrostriatal system is discussed. PMID- 1871187 TI - Acute morphine dependence in the hamster. AB - Two experiments investigated naloxone-precipitated withdrawal following a brief course of morphine administration in hamsters. In Experiment 1, observable withdrawal symptoms (e.g., wet-dog shakes) were elicited by two doses of naloxone (0.4 and 1.0 mg/kg) following four and eight daily injections of morphine (15 mg/kg), a regimen that replicated previous studies in our laboratory using a locomotor activity paradigm. At the lower dose of naloxone, the frequency of withdrawal signs was greater after eight than after four morphine injections. In Experiment 2, observable withdrawal symptoms were elicited by the same two doses of naloxone, 70 min after a single morphine injection. These results suggest that acute dependence in the hamster, as in other species, beings to develop with the first morphine exposure. PMID- 1871188 TI - Behavioral economic analysis of smoking: money and food as alternatives. AB - The relative reinforcing value of smoking versus two nonpharmacological reinforcers, money and food, was evaluated in young female smokers in two experiments. In Experiment 1 eight smokers worked for access to smoking or money on concurrent progressive variable ratio schedules of reinforcement (VR4 to VR50) across two days of Smoking Deprivation or No Deprivation. During No Deprivation money was reliably chosen over smoking. During Deprivation subjects initially (VR4) chose smoking over money, but at subsequent comparisons allocated equal time to work for smoking or money. In Experiment 2 eight smokers were provided access to smoking or food across four conditions: No Deprivation, Smoking Deprivation, Food Deprivation and Smoking + Food Deprivation, using the same progressive variable ratio schedules as in Experiment 1. Results showed an increase in the reinforcing value of food after Food Deprivation and smoking after Smoking Deprivation. On the dual deprivation day, subjects initially (VR4) chose to work for food, showed equal preferences over the next three schedule comparisons (VR8-VR20), and from VR25-VR50 shifted their choice to smoking. An increase in percent of calories as fat was observed during all deprivation conditions. The results demonstrate the use of the concurrent schedule paradigm for assessing choice among pharmacological and nonpharmacological reinforcers, and shows the relative reinforcing value of smoking depends on recent deprivation, response demands to obtain the reinforcer and availability of alternative reinforcers. PMID- 1871189 TI - Cholinergic activity in the rat hippocampus, cortex and striatum correlates with locomotor activity: an in vivo microdialysis study. AB - The possible relationship between behavioral arousal and acetylcholine release in the striatum, hippocampus and frontal cortex was investigated in rats. In vivo microdialysate concentrations of acetylcholine and choline from these brain structures, and photocell beam interruptions (as a measure of behavioral arousal), were measured simultaneously under three conditions: after injections of 1) vehicle or 2) scopolamine (0.4 mg/kg), and 3) before and after the beginning of the rats' night cycle. Dialysate concentrations of ACh in all 3 brain structures and locomotor activity were increased after scopolamine and the onset of the lights out condition. Vehicle injections transiently increased ACh in the hippocampus and cortex and caused short-lasting increases in locomotor activity. Under all conditions, the release of ACh from each of the 3 brain structures correlated with the level of locomotor activity. PMID- 1871190 TI - The circling training rat model as a behavioral teratology test. AB - The properties of circling training (CT) for detecting behavioral teratologic drug-induced effects was evaluated by prenatal administration of two behavioral teratogenic drugs: vitamin A (80,000 IU/kg/day) and haloperidol (2.5 mg/kg/day). The circling training was started at 30 days of age and performed for 8 days in an automated apparatus. Statistically significant differences between drug treated and control animals regarding the measured response (turns per minute) were found. Two components may affect the response measured by the CT: associative learning and motor performance. The incidence of these components was discriminated with behavioral and mathematical approaches. In the experimental conditions used the most affected parameter was motor performance. The results indicate that CT can be used as an instrumental conditioning test where the quantifiable endpoint is the on-going motor performance. Further applications of the CT for neurochemical evaluation of drug induced effects are also discussed. PMID- 1871191 TI - Effect of eseroline on schedule-controlled behavior in the rat. AB - Male Sprague-Dawley rats were trained to press a lever on a simple-alternation multiple fixed-ratio (FR) 20-response time-out (TO) schedule for water reinforcement. Twelve 5-min periods of FR reinforcement were each followed by a 5 min TO in which responding had no scheduled consequence. Doses ranging from 0.25 to 8 mg/kg of eseroline, the hydrolysis product of eserine and a potent analgesic agent with weak anticholinesterase activity, were administered SC immediately prior to a 120-min test session. Eseroline produced a dose-dependent monotonic decrease in the number of reinforcements, with significant effects at doses of 1, 2, 4 and 8 mg/kg and an ED50 of 2.5 (1.6-3.4) mg/kg. This behavioral disruption was characterized by a rapid onset of pausing (i.e., within 5 min postdosing) and a gradual recovery to normal baseline levels of responding over the remaining session time. The duration of the rate decreasing effects was dose-related with the highest dose having a mean duration of more than 60 min, which was longer than that of previous reports on antinociception produced by eseroline (less than 60 min). The coadministration of behaviorally inactive doses of the opiate antagonist naloxone (1 and 2 mg/kg, IP) with eseroline (2.5 mg/kg, ED50) antagonized the effects of eseroline on the operant behavior. The coadministration of behaviorally inactive doses of the muscarinic antagonist atropine with eseroline (2.5 mg/kg) did not affect eseroline's behavioral effect. These results suggest that the effects of eseroline on operant behavior is consistent with the effects of eseroline-induced antinociception, reported previously, and appears to be associated with the activation of opiate receptors, but not related to the stimulation of muscarinic receptors via its anticholinesterase activity. PMID- 1871192 TI - Effects of eltoprazine hydrochloride on exploratory behavior and social attraction in mice. AB - The effects of eltoprazine (DU 28853) on exploratory behavior and conspecific social attraction were examined in four experiments. Drug treatments somewhat enhanced three forms of exploratory behavior but decreased social attraction. The results indicate that eltoprazine, in sharp contrast to fluprazine, weakly ameliorates neophobic responses. Both eltoprazine and fluprazine seem to increase the aversiveness of encounters with other organisms, however. The latter effects may be mediated, in part at least, by some alteration in olfactory function. PMID- 1871193 TI - Pituitary and brain beta-endorphin in male and female rats: effects of shock and cues associated with shock. AB - The present experiment was designed to study whether or not prior exposure to inescapable shock is accompanied by sex-dependent changes in pituitary and central levels of immunoreactive beta-endorphin, which is proposed to play an important role in opioid analgesia induced by aversive stimulation. Further, the effects of brief reexposure (5 min) to the chamber where inescapable shock was experienced earlier, were established in both sexes. Elevated levels of beta endorphin were found 24 hours after inescapable shock, in the anterior pituitary of males and in the midbrain periaqueductal gray of both males and females. Reexposure to the experimental chamber only affected beta-endorphin levels if shock had been experienced in this chamber. Reexposure after inescapable shock reduced beta-endorphin content of the arcuate nucleus of males and beta-endorphin content of the periaqueductal gray of males and females. The present results are related to previous findings of sensitization and conditioning of analgesic reactions. The sex differences found in the present experiment are discussed with respect to sex-dependent behavioral consequences of inescapable shock. PMID- 1871194 TI - Differential role of serotonin and noradrenaline on anxiety reduction after ejaculation in the rat. AB - As previously reported, a reduction in anxiety after ejaculation was observed. In a previous report it was demonstrated that the GABA-benzodiazepine system is involved in the mediation of this reduction in anxiety. The anxiety levels were measured using a defensive burying model. This work was performed to elucidate the serotonin and noradrenaline participation in the mediation of this phenomenon. Two experiments were made. In the first experiment the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, 10 micrograms/10 microliters) was intracerebroventricularly injected. Five days after its administration the behavioral tests were performed. In the second experiment, the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4, 50 mg/kg X 2) was IP administered. The neurochemical data reveal a drastic reduction in various brain areas respective monoamine levels after these treatments. The lesion produced by 5,7-DHT was able to reverse the reduction in anxiety in copulating males, but produced no changes in noncopulating animals. This finding supports the idea that the serotonergic system is involved in the reduction of anxiety observed after ejaculation. The results of the DSP4 experiment suggest that there is not a direct participation of the noradrenergic system in the anxiety reduction observed after ejaculation. PMID- 1871195 TI - Cold swimming stress: effects on serum lipids, lipoproteins and LCAT activity in male and female rats. AB - Effects of consistent cold swimming stress on lipid and lipoprotein metabolism parameters were studied using male and female rats over a period of 60 and 20 days respectively. At the end of treatment serum total cholesterol, high density lipoproteins (HDL-C) and lecithin:cholesterol acetyltransferase (LCAT) activity declined in both male and female rats. TC/HDL-C ratio declined in 20 days in females, while in males it did not change. Free fatty acids increased, while triglycerides remained unchanged in both sexes. %Lipoprotein distribution in male animals did not show any phenotype alteration except in the group of 40 days where %VLDL declined and %LDL-C increased. Body weights did not change, except in males in 60 days. Consistent cold swimming stress by lowering HDL-C and LCAT activity seems to influence lipoprotein metabolism. PMID- 1871196 TI - Morphine effects on mouse locomotor/exploratory activity: test dependency, test reliability, uni- and multi-variate analyses. AB - Drug and toxicant effects on locomotor/exploratory activity can be quite variable depending on the test and the schedule of exposure. In neurobehavioral toxicology and teratology, these interactions can affect the inferences based on the use of selected drugs as probes to assess which regulatory mechanisms are affected by one or the other treatment. The present experiments were aimed at comparing morphine effects in CD-1 mice under three conditions, namely, Varimex apparatus (VAR), toggle floor box (TOGGLE), videotape recording (VIDEO) in a home cage environment. Morphine HCI (0, 10, 33, or 100 mg/kg) was given IP 20 min before the start of a 30-min test session. The same procedure was repeated 24 h later. Results of VAR and TOGGLE tests were: dose 10 was largely ineffective; dose 33 induced depression in VAR and hyperactivity in TOGGLE; dose 100 enhanced activity in TOGGLE. There were no differences between session 1 and 2. VIDEO: Univariate analysis results showed that morphine produced a dose-dependent depression of Rearing and Grooming, and an enhancement of Crossing, again without changes due to repeated exposure. Results of Principal Component Analysis supported a response competition model of the changes observed in the mouse behavioral profile. The videorecording (VIDEO) procedure is the one providing the most accurate picture of changes in locomotor/exploratory activity and drug effects thereon, also allowing a more comprehensive statistical analysis of the relationships between various types of response changes. PMID- 1871197 TI - Behavioral tolerance to flurazepam. AB - Rats were trained to earn 180 food pellets in daily, fixed-interval 1-min sessions. When performance had stabilized, a Before group was given a weekly 16 mg/kg flurazepam injection IP for 3 weeks immediately before the sessions, while an After group received their weekly injections immediately after the sessions. Then, the After group received 3 such weekly injections before the sessions. Behavioral tolerance developed by the 2nd flurazepam injection for the Before group, but for the After group, the 3 postsession flurazepam injections resulted in subsequent tolerance to presession flurazepam injection for session lever presses, but not for the time taken to earn 180 pellets. Dispositional tolerance to the serum elimination rate of flurazepam did not develop over the course of 3 injections. Behavioral suppression still evident in the initial portion of sessions with the 2nd and 3rd presession injection coincided with the duration of rising and high levels of serum flurazepam. PMID- 1871198 TI - Changes in blood pressure and dipsogenic responsiveness to angiotensin II during chronic exposure of rats to cold. AB - Hypertension accompanies chronic exposure of rats to cold (5-6 degrees C). Systolic, diastolic, and mean blood pressures become elevated, and hypertrophy of the heart occurs. A previous study from this laboratory suggested that the renin angiotensin system may play a role. The present study was carried out to assess this further. Thus, in addition to measurement of systolic blood pressure at intervals during exposure to cold, plasma renin activity and the dipsogenic responsiveness to acute administration of angiotensin II were also measured to assess the functional status of the renin-angiotensin system. The results showed a significant (p less than 0.05) increase in systolic blood pressure during the third week of exposure to cold. In contrast, plasma renin activity (PRA) increased within the first week of exposure to cold, and declined thereafter to reach the level of the control by the third week of exposure to cold. By the fourth week, PRA decreased to a level significantly (p less than 0.05) below that of the control group. The responsiveness to acute administration of angiotensin II (AII), as assessed by the drinking response, increased significantly (p less than 0.05) by the third week of exposure to cold and remained significantly elevated during the fourth week. There was a significant (p less than 0.01) direct relationship between dipsogenic responsiveness to AII and blood pressure in the cold-treated (r = .57), but not the control group (r = .12). There was also a significant (r = -.91) indirect linear relationship between PRA and dipsogenic responsiveness to AII. Cold-treated rats had significant increases in urinary norepinephrine output and weights of heart, kidneys, adrenals, and brown adipose tissue characteristic of rats acclimated to cold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871199 TI - Desensitization of central nicotinic cardiovascular effects by nicotine isomers and a quaternary analogue. AB - Nicotine produces potent cardiovascular and sympathoadrenal effects. Furthermore, repeated administration of nicotine is associated with development of tolerance for many responses. We sought to compare the effects of initial intracerebral administration of nicotine isomers and a quaternary analogue on cardiovascular and sympathoadrenal responses and to compare the desensitizing properties of these nicotinic compounds on subsequent responses to nicotine. Thus we examined the effects of (-)-nicotine, (+)-nicotine, N'-methylnicotinium iodide (N'MN), a quaternary analogue of (-)-nicotine, and saline vehicle, administered into a lateral cerebral ventricle, on heart rate (HR), systolic, diastolic and mean arterial blood pressure (BP), and plasma concentrations of epinephrine and norepinephrine in conscious, freely moving, adult, male rats. (-)-Nicotine (120 nmol, ICV) produced decrease in HR and increases in all other parameters. (+) Nicotine at this dose produced only small effects on HR, BP and plasma catecholamines. An equimolar dose of N'MN produced similar effects on these parameters, quantitatively intermediate between those of the two nicotine isomers. Thirty min after administration of these nicotinic agonists, all parameters had returned to baseline. At this time, the effects of subsequent ICV administration of (-)-nicotine 120 nmol was studied in all animals. Prior administration of either (-)-nicotine or (+)-nicotine markedly attenuated the bradycardic response to (-)-nicotine, and N'MN was less effective in this regard. In contrast, neither (-)-nicotine nor N'MN inhibited the pressor response to subsequent (-)-nicotine, whereas (+)-nicotine did produce some attenuation of this pressor response. Similarly, only (+)-nicotine, was found to inhibit the plasma norepinephrine response to subsequent (-)-nicotine when this drug dose and timing of administration were used. The epinephrine response to subsequent (-) nicotine was not affected by this dose (120 nmol) and timing of treatment with any of these ligands. These data support the concept that desensitization of the intracerebral effects of nicotine on cardiovascular and sympathoadrenal function may be mediated at binding sites other than those producing nicotinic responses. PMID- 1871200 TI - Nicotine potentiates haloperidol-induced catalepsy and locomotor hypoactivity. AB - Nicotine was found to potentiate the catalepsy and reduced locomotion following the administration of haloperidol. The ability of various doses of nicotine (0.1, 0.2, or 0.3 mg/kg) to potentiate the catalepsy produced by haloperidol (0.1, 0.2 or 0.4 mg/kg) was investigated. Nicotine potentiated the cataleptic effects of both the 0.2 and 0.4 mg/kg doses of haloperidol, but had no effect following the lowest (0.1 mg/kg) dose of haloperidol. The nicotine potentiation of catalepsy produced by the highest dose of haloperidol was independent of the dose of nicotine used. Nicotine alone did not produce catalepsy. A second experiment evaluated the ability of nicotine to potentiate the decreases in spontaneous locomotor activity produced by haloperidol. Animals received nicotine (0.1 mg/kg) alone or in conjunction with haloperidol (0.1 or 0.4 mg/kg) and were tested in Digiscan Animal Monitors. Haloperidol produced a dose-related decrease in locomotion. Nicotine significantly potentiated the hypoactivity produced by both doses of haloperidol. These results indicated that: 1) nicotine produces a significant potentiation of both the catalepsy and locomotor decreases following haloperidol and 2) the Digiscam Animal Activity Monitors may provide a more sensitive assessment of the interaction between nicotine and haloperidol than the catalepsy bat test. These data suggest that adjunct treatment with nicotine may prove useful for treating neuroleptic responsive disorders such as Tourette Syndrome, schizophrenia and Huntington's disease. PMID- 1871201 TI - Measuring anxiety in nonhuman primates: effect of lorazepam on macaque scratching. AB - Lorazepam (0.2 mg/kg IM) was given to group-living female macaques to assess the effect of anxiolytic treatment on scratching, a behavior pattern referred to as a displacement activity in the primate literature. Lorazepam selectively diminished scratching behavior. The drug effect was status-dependent: especially low-ranking animals showed a marked reduction in scratching. Lorazepam exerted a direct effect on scratching, that is the effect was not due to sedation or mediated by the influence of the drug on other behaviors. These results provide pharmacological validation to the ethological finding that scratching may be a manifestation of anxiety in monkeys. In addition, they suggest to use scratching as a behavioral measure in studies investigating nonhuman primate models of anxiety. PMID- 1871202 TI - Cocaine toxicity: genetic differences in cocaine-induced lethality in rats. AB - Cocaine produces stimulation, depression, convulsions and death, and binds at several receptor sites. Thus cocaine may produce toxicity through similar or distinct pathways from those associated with stimulation. Genetic differences in stimulant response to cocaine have recently been reported for four inbred rat strains, ACI, F344, LEW and NBR. In the present study, significant genetic differences were found in cocaine-induced lethality, with a two-fold difference in LD50 values seen between the most sensitive (NBR) and least sensitive (LEW) strains. Sensitivity to lethality was not correlated with sensitivity to stimulation, but was highly correlated with baseline activity. This lack of strong association between stimulant and lethal effects of cocaine may be important in clinical manifestations of the cocaine sudden death syndrome. PMID- 1871203 TI - Orally delivered cocaine functions as a positive reinforcer in C57BL/6J mice. AB - Cocaine serves as a reinforcer across several routes of administration and species. However, whether orally delivered cocaine serves as a positive reinforcer has not been systematically established. We determined the extent to which contingent access to orally delivered cocaine would maintain lever pressing behavior in C57BL/6J mice who had a prior history of operant ethanol-reinforced behavior. The findings presented in this report demonstrate that orally delivered cocaine can serve as a reinforcer of operant behavior. A drug substitution procedure where cocaine was substituted for gradually decreasing ethanol concentrations was successful in inducing pharmacologically significant intakes of cocaine under a fixed ratio (FR) schedule of drug access. When ethanol was removed, responding for cocaine continued. As FR size was increased, proportionate increases in responding occurred except at the highest FR value. Responding maintained by cocaine significantly exceeded responding maintained by vehicle, with the mice typically consuming 6-10 mg/kg cocaine per 30-min session. The utilization of inbred strains and the procedures followed in the present studies should prove useful in determining the extent of both genetic and environmental influences on various behavioral effects of cocaine and their mechanisms of action. PMID- 1871204 TI - Drinking behavior in the spiny mouse (Acomys cahirinus) following putative dipsogenic challenges. AB - Male spiny mice (Acomys cahirinus) were challenged with several putative dipsogenic stimulus conditions: hypertonic sodium chloride (NaCl), 24-h water deprivation, d,l-isoproterenol HCl, angiotensin II (AII) and polyethylene glycol (PEG), or control conditions, in within-subjects designs. Water intake and drinking pattern were monitored electronically in the home cage over a 2--6-h test period without food present, during the light portion of the L/D cycle. In addition, hematocrits were measured following several treatments and mean arterial blood pressure was monitored in response to several doses of AII. As expected, both water deprivation and hypertonic NaCl led to robust drinking with short latencies. PEG was also an effective dipsogen; while quite variable, latencies were often shorter than are typically reported for the rat. Isoproterenol induced a modest, but significant, dose-related drinking. Interference by AII's prominent pressor action might account, at least in part, for its relative ineffectiveness as a dipsogen. Comparisons are made with other rodent species similarly challenged. PMID- 1871205 TI - Metoclopramide decreases apomorphine-induced yawning and penile erection. AB - Acute administration of metoclopramide, a dopamine (D2) antagonist, reduced both apomorphine-induced yawning and penile erections. Metoclopramide, prominent in clinical use as an effective antiemetic, has been shown to be associated with decreased erectile function in humans. Experimentally naive rats were given a standardized dose of apomorphine and one of a range of doses of metoclopramide. The study shows that metoclopramide decreases the erectile response to apomorphine and suggests that the erectile difficulties experienced in humans after metoclopramide treatment may be a result of interference with a central dopaminergic mechanism(s). PMID- 1871206 TI - Nicotine improves cognitive disturbance in rodents fed with a choline-deficient diet. AB - The effect of nicotine on learning disturbances was tested in rats. Rats were fed either a choline-enriched or a choline-deficient diet. Concentration of acetylcholine in the whole brain was significantly lower in rats fed with choline deficient diet than rats fed with choline-enriched diet. Passive avoidance learning shows that rats on a choline-deficient diet showed significantly impaired learning compared to rats on a choline-enriched diet. Nicotine (0.04 mg/kg) administered intraperitoneally significantly potentiated learning in rats on a choline-deficient diet, as well as in rats on a choline-enriched diet. We, therefore, suggest that nicotine may potentiate learning in an acetylcholine deprived brain. PMID- 1871207 TI - A silicone pellet for continuous cocaine: comparison with continuous amphetamine. AB - An inexpensive silicone pellet is described for the continuous administration of cocaine for up to 5 days. Rats implanted with this pellet show minimal skin irritation and go through distinct behavioral stages, with an initial period of hyperactivity followed by motor stereotypies. Then, at 3-4 days after implantation, a variety of hallucinogen-like ("late-stage") behaviors appear, including limb flicks, sudden startle responses, and repetitive mid-air grasping movements. Compared to continuous d-amphetamine, continuous cocaine induces decreased motor stereotypies but heightened "late-stage" behaviors. PMID- 1871208 TI - Medical physics, in the past, today and in the future--the development of medical physics from the point of view of a radiologist. PMID- 1871209 TI - Analysis of texture in macroradiographs of osteoarthritic knees using the fractal signature. AB - Texture of regions of macroradiographs (x5) of six normal and five osteoarthritic knee joints, taken on a high resolution microfocal x-ray unit, are examined using mathematical morphology. Radiographs of bones are two-dimensional projections of attenuation coefficient through the three-dimensional (3D) joint structure. Visible texture represents the summation of the attenuation from numerous thin plates of bone. Where there is no organization in the trabeculae, resultant radiographs approximate a fractal surface. Varying structuring element size in mathematical morphology allows estimation of fractal dimension over a range of resolution. Variation of fractal dimension with resolution, the fractal signature, indicates how images deviate from fractal surfaces. By correct choice of structuring element, a texture analysis method using the fractal signature has been developed, tolerant to changes in image acquisition and digitization. Texture in regions of radiographs of normal tibia approximates a fractal surface with dimension 2.8 as does vertical structure in arthritic patients. In osteoarthritic knee joints, horizontal tibial trabeculae thicken. Horizontal structure in the tibia on radiographs of arthritic patients deviates from the fractal model. This is indicated by peaks in the fractal signature whose height and position match a visual assessment of the degree of arthritic change. PMID- 1871210 TI - Accurate Monte Carlo calculations of the combined attenuation and build-up factors, for energies (20-1500 keV) and distances (0-10 cm) relevant in brachytherapy. AB - The combined build-up and attenuation factor, B exp (-mu r), of point isotropic photon sources in a water medium has been calculated using the Monte Carlo method, for energies (20-1500 keV) and distances (1-10 cm) relevant in brachytherapy. For the transport of photons and electrons, up-to-date and self consistent total, partial and differential cross sections were used. The influence of coherent (Rayleigh) and incoherent (Compton) scattering, as well as the effects of the source and medium geometries on the calculations, were investigated in detail and it was found that these effects can lead to significant deviations from published data, especially at low energies and/or large distances from the sources. Our results can be used for any mono- or multi energetic photon source in the energy range 20-1500 keV with uncertainties of the order of 2-3%, and they may influence treatment planning especially in the case of organs at risk which are usually near the edge of the body. PMID- 1871211 TI - In vivo measurement of the optical interaction coefficients of human tumours at 630 nm. AB - The light distribution within a treatment volume is determined by the source geometry (e.g. superficial or interstitial illumination) and the optical interaction coefficients of the irradiated tissue. We have measured the energy fluence rate at various points within tumours undergoing irradiation with 630 nm light for photodynamic therapy for several source geometries. The relative positions of source and detector fibres were determined using CT scanning techniques. The results of the measurements were then applied to solutions of the diffusion theory which allowed the determination of the absorption coefficient (sigma a = 30.5 +/- 16 m-1), the reduced scattering coefficient (sigma' s = 941 +/- 735 m-1), the effective attenuation coefficient (sigma eff = 261 +/- 49 m-1) and the build-up coefficient which relates surface irradiance to the energy fluence rate at depth (k = 1.6 +/- 0.6). Knowledge of these coefficients allows the transmission of light through tissue to be predicted and hence the optical dosimetry of subsequent treatments to be planned more effectively. PMID- 1871212 TI - Interstitial heating: experiments in artificially perfused bovine tongues. AB - Isolated perfused bovine tongues were heated with a 2 x 2 hot water tube interstitial hyperthermia system (tube outer diameter 2.0 mm, spacing 16 mm). Tongue blood flow ranged between 0 and 17 ml min-1/100 g. The temperature distribution was mapped with 5 to 8 single thermocouples (diameter 50 microns). Model predictions using both the conventional bioheat transfer equation and the effective conductivity model were compared to the experimental results, with emphasis on the role of blood flow. Results indicate a better qualitative agreement with the k-effective model than with the heat sink model. In this set up a 16 mm spacing proved sufficient for adequate heating between the needles at normal blood flow rates, in the absence of large vessels. PMID- 1871213 TI - A perfusion technique for tongues to be used in bioheat transfer studies. PMID- 1871214 TI - Glandular excision in total glandular mastectomy and modified radical mastectomy: a comparison. AB - Total glandular mastectomy and modified radical mastectomy were compared for the amount of breast tissue remaining after surgery. Multiple biopsies were taken from the anterior chest walls of women following total glandular mastectomy (N = 27) and modified radical mastectomy (N = 28) to try to detect any residual glandular tissue. Regardless of procedure performed, breast tissue was identified histologically in 5 percent of all biopsy specimens (159 and 161, respectively). One of every five operative fields was shown to have glandular elements in at least one of the biopsy sites; the positive biopsies did not form a discernible pattern. The residual breast tissue in each of these patients averaged less than 1 gm. On the basis of this study, modified radical mastectomy and total glandular mastectomy appear to be equally effective in removing most of the breast. PMID- 1871215 TI - The effect of rigid fixation on growth of the neurocranium. AB - The effects on skull growth of plating the coronal suture and frontal bone were studied in New Zealand White rabbits. Three-dimensional coordinate landmarks were digitized and analyzed to determine the differences in form between operated and unoperated animals using Euclidian distance matrix analysis. This method compares sets of interlandmark distances in three dimensions and was used to demonstrate changes induced by plating. We interpret these changes in morphology to be the result of differences in growth between the operated and unoperated groups. Periosteal elevation alone (n = 6) resulted in a minimal local growth increase. Coronal suture plating (n = 8) resulted in local growth restriction with contralateral and adjacent size increases. Frontal bone plating (n = 6) without crossing a suture line also resulted in local growth restriction and adjacent bone size increases. The timing of intervention in relation to the completion of bone growth may explain the magnitude of clinically apparent effects. Changes in bones adjacent to those directly manipulated may be an attempt to maintain a normal skull volume. PMID- 1871216 TI - A single-stage two-flap method of total ear reconstruction. AB - A single-stage two-flap method of total ear reconstruction in congenital microtia is reported. This method was derived from the one-stage reconstruction described by Song and Song. Two flaps defined by vascular basis were elevated on the mastoid area: the superficial skin flap supplied mainly by subcutaneous pedicled arteriole perforators from the posterior auricular artery and the deeper axial pattern fascial flap including the posterior auricular artery itself. The ear framework, exaggeratedly carved using autologous rib cartilage, could be inserted easily between the two flaps, simultaneously producing the auriculocephalic angle and the conchal wall. Intraoperative expansion of the skin flap and postoperative external ear molding also were performed to create aesthetically pleasing ears. PMID- 1871217 TI - Growth status of children treated for unilateral cleft lip and palate. AB - Cephalometric distances, angles, and proportions were evaluated for 32 children 5 to 8 years of age treated for unilateral cleft lip and palate. The children were age and sex matched with untreated controls with normal skeletal relationships. The unilateral cleft lip and palate sample was treated by the same surgeon and orthodontist using the same techniques and appliances. Measures of overall facial proportions, facial convexity, and prognathism were not significantly different between the two groups. The primary group differences pertain to the posterior aspect of the maxilla, which is vertically short in the unilateral cleft lip and palate sample. Horizontally, the maxilla of the unilateral cleft lip and palate children was significantly longer, producing a steeper palatal plane. In addition, the zygoma and orbits of unilateral cleft lip and palate children were somewhat retruded; the posterior cranial base and total mandibular length also were longer in the unilateral cleft lip and palate children. PMID- 1871218 TI - The modified buccal musculomucosal flap method for cleft palate surgery. AB - We have reported previously on a palatoplasty method, called the T-shaped musculomucosal buccal flap method, for the primary repair of a cleft palate. This method has been used on more than 90 patients, and satisfactory outcomes have resulted in terms of maxillar development, the prevention of fistulation, and verbal functions. However, 14.3 percent of these patients exhibited a velopharyngeal incompetence that showed no potential improvement through training. In the majority of these patients, the entire raw surface of the oral cavity side could not be covered with a buccal musculomucosal flap, and as a result, postoperative contraction of the soft palate occurred. Thus a new surgical method has proven effective in which both buccal musculomucosal flaps are used as an oral lining, the nasal mucosa having been extended by Z-plasty. We have performed 25 operations using this new method and have observed no postoperative contractions of the soft palate, notwithstanding two cases (8.0 percent) of postoperative fistulation. PMID- 1871219 TI - The biomechanical effects of deep tissue support as related to brow and facelift procedures. AB - The adverse effects of increased tension across a healing wound are well known. However, the effect of closing a wound in layers in order to decrease tension on the epidermis has been a source of controversy. It is hypothesized that deep tissue support decreases skin tension upon wound closure. In order to clarify this issue, a two-part study was designed to address the immediate effects of deep tissue support in vitro using fresh-frozen cadavers and in vivo on patients undergoing scheduled surgery. Closing skin tension was measured at standard reference points in coronal brow lift and rhytidectomy procedures performed with and without galeal closure and superficial musculoaponeurotic system (SMAS) procedures, respectively. Deep tissue support was found to significantly (p less than 0.05) decrease skin tension at the time of skin closure at standard reference points in coronal brow lift and rhytidectomy procedures performed on fresh-frozen cadavers. Similar significant (p less than 0.05) decreases in closing skin tension also were found in vivo in patients undergoing similar surgical procedures. Stress relaxation was not found to play a significant role in contributing to this immediate decrease in closing skin tension. It would appear, therefore, that deep tissue support, in the form of galeal closure and an SMAS procedure in coronal brow lift and rhytidectomy procedures, respectively, provides increased viscoelastic support, producing immediate significant decreases in closing skin tension in these procedures. The beneficial effects on wound healing, scar formation, tension-related trophic skin changes, and possible improved long-term results are discussed. PMID- 1871220 TI - Curette fat sculpture in rhytidectomy: improving the nasolabial and labiomandibular folds. AB - The nasolabial and labiomandibular folds develop with facial aging by an anterior caudal descent of the fat prominences of the same name. Young patients with minimal folding can be corrected by substances inserted in the fold; however, this and other techniques have failed satisfactorily to improve the folds naturally and permanently. Identification of the prominences and removal of the fat superficial to the skin by curettes have proven safe and effective and superior to fat suction. Complications include small hematomas and visible depressions in the sculpted areas. There was no nerve or skin injury. Follow-up of this technique (an improvement of a previous technique) is 3 1/2 years. PMID- 1871221 TI - Late bleeding after rhytidectomy from injury to the superficial temporal vessels. AB - Five healthy, normotensive women, whose mean age was 49.8 years, developed expanding hematomas between 8 and 10 days (average 9 days) after rhytidectomy. In each patient, the bleeding vessel could be identified: In two, it was the parietal branch of the superficial temporal artery; in two, it was the parietal branch of the superficial temporal vein; and in one, it was the superficial temporal artery immediately before its branching. Contributing factors may have been sudden physical exertion in four of the five patients and in another salicylate ingestion. Several measures can help avoid late bleeding from the superficial temporal vessels or their branches; not using a too potent vasoconstrictive agent (epinephrine) in the local anesthetic so that the vessels will be easier to visualize; not injecting the local anesthetic too deeply or incising to deeply; dividing and ligating the superficial temporal vessel and its major branches if injured; using bipolar coagulation on small branches; and instructing patients repeatedly not to engage in strenuous activity or to ingest salicylates for at least 2 weeks after operation. PMID- 1871222 TI - Surgical depilation for the treatment of pseudofolliculitis or local hirsutism of the face: experience in the first 40 patients. AB - Forty patients underwent surgical depilation for pseudofolliculitis barbae or local hirsutism of the face during a 15-year period. The operative method and its results and pitfalls are discussed. Although it is not the treatment of choice, this operation is very useful when other therapy has not been successful. This seems especially true in male-to-female transsexuals. PMID- 1871223 TI - Intraoral reconstruction with a microvascular peritoneal flap. AB - The microvascular peritoneal flap offers a new reconstructive option for closure of intraoral defects. The flap is easy to raise, and donor-site morbidity is low. Unlike fascial flaps, in which the raw surface may take weeks to "mucosalize," the peritoneal surface heals primarily. Finally, the rectus muscle effectively covers all forms of mandibular reconstruction, and the reliable skin paddle makes possible the closure of substantial cutaneous defects. PMID- 1871224 TI - Long-term complications of polyurethane-covered breast implants. AB - The authors's personal experience using an earlier manufactured polyurethane covered gel prosthesis is presented. Very long-term follow-up did not validate the author's initial enthusiasm. It is to be hoped that the newer polyurethane covered implants will give more satisfactory long-term results. PMID- 1871225 TI - Biocompatibility of radiolucent breast implants. AB - Current implants for breast augmentation containing silicone gel, saline, or both are radiopaque on mammographic examination and can totally obscure microcalcifications and soft-tissue masses. The effect of these implants on the detection of early breast cancers in patients who have undergone augmentation mammaplasty remains unproven and controversial. Implants filled with medium-chain triglycerides (peanut oil) are radiolucent on mammographic examination and allow visualization of both soft-tissue masses and microcalcifications. To investigate the biocompatibility of radiolucent implants, 10 cc of sterile, nonpyrogenic peanut oil was injected subcutaneously into rats using silicone gel as a control. Twenty-one rabbits had two 125-cc silicone shell implants inserted on either side of the chest wall. The right-sided shell was filled with 125 cc of sterile saline, and the left-sided shell was filled with 125 cc of sterile, nonpyrogenic peanut oil. Results were determined by both histologic and radiographic examination. Rats injected with peanut oil equivalent to 7 percent of their body weight rapidly absorbed the freely injected oil without detriment. Histologic examination of the lungs, liver, kidneys, and tissues adjacent to the injection sites demonstrated no abnormalities. There was no evidence of allergic, toxic, inflammatory, or neoplastic response. Eighteen of 21 rabbits survived more than 3 months. Radiographs showed the oil-filled implants to be radiolucent, whereas the saline-filled controls obscured the surrounding soft and bony tissues. Histologic examination demonstrated a fibrous capsule surrounding both types of implants. Histologic examination of the lungs, liver, and kidneys showed no significant abnormalities. These and previous studies have shown peanut oil to be biocompatible when freely injected either intramuscularly or subcutaneously. This study demonstrates that a radiolucent, peanut oil-filled implant is biocompatible in animals and that further long-term studies for its use in humans are merited. PMID- 1871226 TI - Comparative experience with smooth and polyurethane breast implants using the Kaplan-Meier method of survival analysis. AB - Smooth-walled silicone implants have been widely used in breast surgery. Capsular contracture, causing undesirable firmness and spherical deformity, has been a common problem. Recent studies suggest that polyurethane-covered breast implants are associated with a lower incidence of capsular contracture. The statistical methodology employed in some of these studies, however, may be subject to criticism. Between July of 1984 and June of 1990 (72 months), 427 polyurethane breast implants were used in 279 patients and 439 smooth prostheses were used in 250 patients for a variety of aesthetic and reconstructive procedures. The occurrence of capsular contracture was carefully monitored and then analyzed using the Kaplan-Meier method of survival analysis. This method is particularly well suited to analysis of these types of clinical data because it allows for the fact that contractures occur at varying intervals after surgery and that follow up of patients is incomplete. The probability of capsular contracture with smooth walled prostheses was found to be significantly greater than with polyurethane covered implants in each group of patients studied (p less than 0.05). Other complications occurred at a similar rate regardless of prosthesis type. This study supports the belief that polyurethane breast implants have a lower contracture rate; furthermore, it introduces the Kaplan-Meier method for analyzing the outcome of alternative plastic surgical therapies. PMID- 1871227 TI - Mammograms of the reconstructed breast. PMID- 1871228 TI - Purchased medical care: a frequent illusion. PMID- 1871229 TI - Strawberry hemangioma of infancy: early definitive treatment with an argon laser. AB - This report documents the successful treatment of a hemangioma (strawberry hemangioma) at 5 weeks of age with the argon laser. The natural course of strawberry hemangioma of infancy is well known. It begins as a very small spot and develops very rapidly within the first few weeks of life. Many grow to a very large size and produce significant morbidity. It is logical to assume that if these were ablated early, the life cycle could be aborted. The patient of this case study developed two spots that appeared to be typical evolving hemangiomas. One was treated and disappeared. The other was not treated and evolved into a typical strawberry hemangioma that eventually involuted. This would indicate that early treatment holds some promise. PMID- 1871230 TI - A combined rectus abdominis musculocutaneous flap and vascularized iliac bone graft with double vascular pedicles. AB - Although a free vascularized iliac bone graft has been successfully used for the reconstruction of large bone defects, there is a serious problem of how to repair in one stage patients having a large bone defect with a very wide skin defect. A free combined rectus abdominis musculocutaneous flap and vascularized iliac bone graft with double vascular pedicles seems to be one of the most suitable methods for patients having large defects of both bone and skin. Based on our patient, the main advantage of this flap is the extreme width of the skin territory. The pedicle vessels are large and long, and the donor scar can be made in an unexposed area. This flap should be considered for use in one-stage reconstructions of large defects of both bone and skin in the leg region. PMID- 1871231 TI - Thumb replantation after cardiac transplantation. AB - Generally, severe medical illnesses, including chronic immunosuppression and heavy steroid use, have been deemed relative contraindications for replantation surgery. We report the successful replantation of an amputated thumb in a patient who had previously undergone heart transplantation and was on therapeutic immunosuppression. Despite extensive soft-tissue damage and joint involvement, thumb function and sensibility returned to acceptable levels. This case demonstrates that digital bony union, tendon repair healing, and nerve regeneration are not significantly altered by the standard immunosuppressive regimen following major organ transplant. The implications raised by this case for possible transplantation of allograft digits or limbs are discussed in detail. PMID- 1871232 TI - Use of stacked polyurethane-covered mammary implants in aesthetic and reconstructive breast surgery. AB - The use of stacked polyurethane-covered mammary implants has proven useful in improving results in the correction of deficiencies of mammary form and projection that can occur in certain cases of congenital and acquired breast deformity. The method has been used in 57 patients (102 breasts). The rate of significant complications, including seroma, rash, infection, hematoma, and capsular contracture, has been low (1 to 6 percent). Polyurethane-covered implants will maintain their position when used in a stacked system because of their unique biophysical characteristics, which include tissue bonding and a high friction coefficient between the implant surfaces. PMID- 1871233 TI - Toward a more natural breast: the interpolated thoracoepigastric pedicle in breast reconstruction. AB - A method of reconstructing the breast mound after mastectomy using a superiorly based thoracoepigastric pedicle is presented. The advantages of the method are its relative simplicity and its definition of the inframammary fold. It often obviates the need for inflatable expanders. The prime disadvantage is the scar left on the abdominal donor site. PMID- 1871234 TI - The "cricket bat" flap: a one-stage free forearm flap phalloplasty. AB - Total and subtotal penile reconstruction represents a major surgical challenge. We present a new method and two illustrative cases using a modified design of the radial forearm free-tissue transfer: the "cricket bat" flap. PMID- 1871235 TI - Bilateral latissimus dorsi V-Y musculocutaneous flap for closure of a large meningomyelocele. AB - Reconstruction of a large meningomyelocele defect with bilateral latissimus dorsi V-Y musculocutaneous flaps is reported. This procedure provides a reliable, well vascularized soft-tissue coverage over the neural repair with minimum donor-site morbidity. PMID- 1871236 TI - Method for preparing meshed skin grafts without using skin-graft meshers. AB - We have described a method of preparing meshed skin grafts without resorting to use of a skin mesher. The method is applicable when a mesher is not available during an operation. PMID- 1871237 TI - The rigid transparent dome protector: a new dressing for free-tissue transfers and skin grafts. AB - We have presented a transparent, inexpensive, rigid dome that allows a window to the wound, humidity chamber effect to continuously observe difficult skin-grafted wounds or free-tissue transfers allowing constant monitoring by visualization. The dome is inexpensive because it is simply a discarded breast implant package. PMID- 1871238 TI - Avianca flight No. 052 accident: a plastic surgical perspective. AB - The crash of Avianca Airlines flight no. 052 en route to JFK Airport on January 25, 1990, in Cove Neck, New York, resulted in the death of 72 passengers. Eighty nine victims were admitted to 13 regional hospitals. Despite difficult access to the wooded crash site, early warning and prompt response by 37 volunteer fire and rescue units resulted in organized EMS triage and rapid hospital transport. This report reviews the specific injuries incurred, highlights the team management approach to a major aviation accident in a suburban area, and studies the likelihood of accidents of this magnitude. Thirty-eight patients triaged to two level I trauma centers, North Shore University Hospital-Cornell University Medical Center and Nassau County Medical Center, form the basis of this report. Seventeen patients were male; 21 were female. The average patient age was 33 years. Eight patients were children. The average length of stay was 30.9 days (range 2 to greater than 90 days). Twenty-six patients (including nonsurvivors) (68 percent) sustained significant multiple orthopedic injuries. The majority of fractures were open grade II to III tibia-fibula fractures. Bilaterality was commonly seen. Soft-tissue coverage of open long bone fractures was required in 10 patients (11 extremities) and included 3 microvascular muscle transfers, 7 muscle transposition flaps, and 3 skin grafts. Seven patients required open reduction and fixation of complex facial fractures (two of Le Fort II to III type, four of complex naso-orbital-ethmoid type). Plastic surgical repair of complex lacerations was common. Peripheral nerve exploration was required in three patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871239 TI - Blindness and surgery. PMID- 1871240 TI - Autologous fat injection. PMID- 1871241 TI - Submuscular aponeurotic system. PMID- 1871242 TI - Il Condottiere. PMID- 1871243 TI - Judicious turbinectomy. PMID- 1871244 TI - 585 nm for the treatment of port-wine stains. PMID- 1871245 TI - Does interference with mucoperiosteum and palatal bone affect maxillofacial surgery? PMID- 1871246 TI - The magnetic instrument pad as template material. PMID- 1871247 TI - The pulsed-dye laser for port-wine stains. PMID- 1871248 TI - [Psychoanalytic aspects of the poisoned childhood]. AB - The primary assumption of the paper is that the destruction of the environment, in particular the physical poisoning of the human being himself, simultaneously produces a creeping psychological destruction of the subject's inner world, especially in children and youth. On the basis of Melanie Klein's theory, the fate of the mother as persecuting object is examined. Further, the generation change that can be expected through the ecological situation is worked out on the basis of Boszormenyi-Nagy and Spark's family theory concept of loyalty. Using unsystematic materials, the inner object world of the child in the face of the destroyed environment can be depicted, which in turn allows the fear of the future to be interpreted as fear of disintegration. PMID- 1871249 TI - [Psychosocial stresses after hospital admission--a comparison of internal medicine and surgical patients]. AB - 56 patients have been interviewed about their psychosocial situation at the beginning of their treatment in a medical department, 62 patients in a surgical department of a General Hospital. The "medical" patients were severely disturbed by their illness and by the different diagnostic and therapeutic procedures, even by routine investigations. The "surgical" patients, who just had been operated, concentrated with their feelings on the surgical operation. The clinical atmosphere and the relation and communication to the hospital staff had similar effects on both groups. Further investigations concerning the illness and the treatment should be specified in the different clinical disciplines, while disturbances by the hospital surrounding can be asked at all patients in the same way. PMID- 1871250 TI - [Stress in the hospital--stresses on nurses and physicians]. AB - A questionnaire study was carried out with 891 physicians and nurses working in 54 different hospitals. The objectives were to assess the main stress situations at work and to find out, under which conditions the stress occurs. The results show that the most important stress situations concern the environmental working conditions and the identification with the patient. Physical complaints of the nurses and physicians exceed the scores of a matched norm sample. The main stress conditions are a low level of professional experience, working hours, working in rotating shifts and having to care for a great proportion of terminally ill patients. About 16% of the nurses and 9% of the physicians have to be considered severely distressed. The results shall serve a basis for providing support programs. PMID- 1871251 TI - [Difficulties of psychosomatic clients in assessing personal emotions and motives: possible consequences for therapeutic treatment]. AB - In this work the degree of explication accomplished in a focusing process by 33 persons suffering psychosomatic disorder was compared with that attained by 33 persons in a control group. On the basis of a general psychological conception of focusing process a therapeutical action model was developed which offers concrete action directives to the therapist to deal with different behaviour patterns of clients. It was argumented that persons who exhibit action-directing motives of which they are not aware or which they do not understand due to their great distance to internal experiencing, run a higher risk to experience massive stresses in their struggle with the environment frequently with psychophysiological dysfunctions. In the experimental part of this work it was shown that, as compared with the probands of the comparison group, this therapy method was less beneficial for persons with psychosomatic ailments both with respect to self-experiencing and assessment by others, in that they less distinctly approached the focusing goal and optimum process characteristics. PMID- 1871252 TI - The radiographic diagnosis of emphysema. AB - There are many findings of emphysema by conventional radiography, but the most reliable and reproducible is that of overinflation, which is best judged by the height and contour of the hemidiaphragm. Even in expert hands, the diagnosis of emphysema by conventional radiography is 65% to 80% accurate, depending to a large degree on the clinical population studied. Although most patients with severe emphysema are diagnosed correctly, only half of those patients with mild to-moderate levels of parenchymal destruction are detected. Emphysema is identified by CT as focal, unmarginated, hypodense areas unassociated with fibrosis. Emphysema also may be detected by computer programs selecting pixels with abnormally low attenuation values. By either method, CT is superior to chest radiography in detection of mild and moderate degrees of emphysema and has detection rates of more than 90% and correlation with extent and severity of disease in more than 80% of patients. CT may be more sensitive to the presence of mild emphysema than pulmonary function tests, which are global indications of lung function. HRCT appears to offer a small, but real, advantage over 10-mm collimation in identification of small areas of emphysema, but areas of emphysema smaller than 0.5 cm in diameter are commonly missed, even with HRCT. Wider use of CT for investigation of relatively asymptomatic smokers may allow early diagnosis of emphysema and provide more information of the natural history of this disease, information that is sorely lacking at this time. Assessment of potential therapy such as smoking cessation or antioxidants will only be possible with widespread use of a method that is of relatively low risk, easy to duplicate, and accurate. PMID- 1871253 TI - Bronchiectasis. AB - Bronchiectasis is important because (1) it predisposes the patient to infection; (2) it may be accompanied by increased bronchial blood flow and hemoptysis; (3) when widespread, it may be associated with significant airway obstruction; and (4) when focal, it may simulate neoplasms and other diseases. The widespread use of computed tomography (CT) for evaluation of lung diseases has revealed that bronchiectasis is common--even in patients who do not have clinical or plain radiographic suspicion of bronchiectasis. The pathology, pathogenesis, and radiographic findings are presented herein. PMID- 1871254 TI - High resolution computed tomography. Technical aspects. AB - High resolution computed tomography (CT) may be defined as thin section (1-2 mm collimation) CT optimized by using a high-spatial-frequency (bone) algorithm. Further improvement of the image may be obtained by targeting the scan to a small field of view. This article reviews the technical aspects that influence the quality of the CT image as well as some of the scanning protocols used in the assessment of patients who have diffuse lung disease. PMID- 1871255 TI - High resolution lung computed tomography. Normal anatomic and pathologic findings. AB - The use of high resolution computed tomography (HRCT) for evaluating the lung parenchyma requires an understanding of normal lung anatomy and the pathologic alterations in anatomy that occur in the presence of disease. Most important is an understanding of the secondary pulmonary lobule; HRCT can show many features of the secondary lobule in both normal and abnormal lungs, and many lung diseases, particularly interstitial diseases, produce characteristic alterations in lobular anatomy. HRCT is capable of diagnosing interstitial abnormalities, air space consolidation airway diseases, and emphysema. PMID- 1871256 TI - Computed tomography of air-space disease. AB - Although computed tomography (CT) has not been used as often in air-space diseases as in interstitial ones, it often provides useful information. Diseases such as early opportunistic pneumonia may be detected by CT before becoming visible on plain radiographs. Also, extent and location are often better defined by CT than by plain radiographs. Accompanying abnormalities such as abscess, lymphadenopathy, and pleural effusion are often clearly demonstrated by CT. This article reviews the CT findings in a variety of air-space diseases, including pneumonia and other infections, radiation pneumonitis and fibrosis, embolism, eosinophilic pneumonia, alveolar proteinosis, bronchioloalveolar carcinoma, lipoid pneumonitis, sarcoidosis, and trauma. PMID- 1871257 TI - Computed tomography in chronic interstitial lung disease. AB - A number of studies have demonstrated that high resolution computed tomography (CT) is superior to the radiography in the assessment of patients who have chronic interstitial lung disease. CT may demonstrate extensive parenchymal disease when the radiograph is normal and may allow for a confident diagnosis when the radiographic findings are nonspecific. Although well over 100 different diseases may involve the pulmonary interstitium, in practice, approximately 10 diseases account for 80% to 90% of all cases. This article reviews the CT manifestations of the most common chronic interstitial lung diseases. PMID- 1871258 TI - Scintigraphic studies of inflammation in diffuse lung disease. AB - 67Ga lung scintigraphy is an established means to assess alveolar inflammation in a wide variety of diffuse lung diseases. It can be used to monitor the extent and activity of the alveolitis during the course of the disease and as a follow-up evaluation to therapy. Although the mechanism of 67Ga localization is not established firmly, the isotope appears to act as a tracer for disturbed protein and cellular fluxes within the interstitium and alveolar spaces. The radiolabeled aerosol study may also be applied to the study of these fluxes as a reflection of inflammation and injury. Although Tc-DTPA clearance studies are highly sensitive to lung injury, they may be too nonspecific to separate lung injury from other physiologic processes effectively. PMID- 1871259 TI - Imaging of diffuse lung diseases. Past, present, and future. AB - For many years the plain chest radiograph was the only imaging modality used in the assessment of patients who had diffuse lung disease. Presently, high resolution computed tomography (CT) and lung scintigraphy play a major role in the assessment of these patients. Use of magnetic resonance (MR) imaging in the assessment of the lung parenchyma has been limited by poor signal-to-noise ratio and physiologic motion. Recent improvements in technique, however, have allowed assessment of patients with diffuse lung disease. It is likely that MR imaging will play an increasing role in the assessment of these patients in the near future. PMID- 1871260 TI - Imaging of diffuse lung diseases. PMID- 1871261 TI - A radiographic approach to diffuse lung disease. AB - The chest radiograph remains the first and foremost imaging modality used in the assessment of patients who have diffuse lung disease. An optimal approach to the radiograph requires an understanding of pulmonary anatomy and pathophysiology of disease. The assessment of the radiograph can be based on an anatomic or a descriptive approach. Associated abnormalities, including pleural effusion, pneumothorax, lymphadenopathy, and so forth, also influence the differential diagnosis. This article presents a basic radiologic approach to diffuse lung diseases. PMID- 1871262 TI - Occupational lung disease. AB - The pneumoconioses, extrinsic allergic alveolitis, lung damage due to irritant gases, fumes, and smoke constitute the occupational lung diseases that affect the lung parenchyma. The pneumoconioses are diseases resulting from the accumulation of dust in the lungs. The ILO has established a standardized system for classification of these pneumoconioses that includes both descriptions of diffuse lung opacities and pleural disease. The most common of the fibrogenic pneumoconioses are silicosis, CWP, and asbestosis. The former two entities are characterized radiographically by the presence of small rounded opacities or nodules in the lung parenchyma. Eggshell calcification may occur in lymph nodes, and eventually the diseases may be complicated by the development of large massive areas of fibrosis in the upper lung zones. Asbestosis, on the other hand, demonstrates small irregular or linear opacities usually confined to the bases of the lungs. It is associated with significant respiratory symptoms and disability. High resolution CT has proved useful in characterizing the parenchymal changes and also in identifying early disease in all of these entities. Berylliosis is a systemic disorder that in its chronic form produces granulomatous disease in the lungs. Radiographically it is characterized by the development of either small rounded or occasionally irregular linear opacities usually confined to the bases. Chemical pneumonitis results from exposure to toxic fumes. The acute reaction may produce diffuse lung injury characterized by air-space disease typical of pulmonary edema. In the chronic form, bronchiolitis obliterans supervenes. This usually is associated with either a normal radiograph or evidence of hyperinflation. Finally, hypersensitivity pneumonitis or extrinsic allergic alveolitis is a response of the lung to inhalation of antigens that may be present in the workplace. Either acute, subacute, or chronic disease may result. In the chronic form, a diffuse reticulonodular pattern with or without associated lymphadenopathy is characteristic. PMID- 1871263 TI - Pulmonary edema and adult respiratory distress syndrome. AB - The pathophysiology and radiographic appearances of hydrostatic and increased permeability pulmonary edema are presented. Both typical and atypical appearances are discussed. The ability of the plain chest radiograph to differentiate between different types of edema is examined. PMID- 1871264 TI - Diffuse pulmonary hemorrhage. AB - Diffuse pulmonary hemorrhage is a syndrome consisting of hemoptysis, anemia, and air-space consolidation. The radiologic appearance is non-specific. Pulmonary hemorrhage may be due to a number of different causes. The differential diagnosis and the diagnostic approach are different in the immunologically intact host as compared with the immunocompromised host. This article reviews the main diagnostic considerations in diffuse pulmonary hemorrhage. PMID- 1871265 TI - Pulmonary angiitis and granulomatosis. AB - The presentation of a patient with multiple pulmonary nodules with or without cavitation and often with signs of a multisystemic vasculitis should suggest one of the pulmonary angiitis and granulomatosis syndromes. The five conditions traditionally considered together in the category of pulmonary angiitis and granulomatosis differ widely in their cause and pathogenesis and are more appropriately considered as variants or relatives of other processes. The radiologic features of this group of diseases, however, are similar, and it is useful to still consider them together. Table 1 summarizes the radiologic features of these conditions. PMID- 1871266 TI - Diffuse lung disease in the current spectrum of immunocompromised hosts (non AIDS). AB - Diffuse lung disease occurring in an immunocompromised patient is a nonspecific finding that may result from one or more of a variety of infectious and noninfectious causes. Patient history and clinical information are essential in narrowing the differential diagnosis, but in most patients, diagnostic procedures must be performed to determine appropriate therapy. Diagnostic possibilities include infection, spread of malignancy, reactions to chemotherapy or radiation, nonspecific interstitial pneumonitis, hemorrhage, and unrelated medical conditions. An understanding of the specific nature of the patient's immunologic defect and underlying disease allows one to predict the most likely organisms in cases of infection. PMID- 1871267 TI - Pulmonary manifestations of AIDs. CT and radiographic correlations. AB - To date, few reports have attempted to correlate plain radiographic findings with computed tomography (CT) in assessing pulmonary disease in patients who have acquired immunodeficiency syndrome (AIDS). This report focuses on the most common pulmonary manifestations, with particular emphasis placed on those entities for which there is a potential role for CT. This includes identification of occult disease, especially the early diagnosis of Pneumocystis carinii pneumonia, as well as identification of unsuspected lung abscesses and cavities; characterization of diffuse parenchymal disease in patients who have abnormal radiographs; identification and characterization of mediastinal lymphadenopathy, especially in differentiating between neoplastic and non-neoplastic causes; and finally, use of CT to perform CT-guided transthoracic needle biopsies. PMID- 1871268 TI - From Thales to Lauterbur, or from the lodestone to MR imaging: magnetism and medicine. PMID- 1871269 TI - Pancreatic adenocarcinoma: are there pathognomonic changes in the fat surrounding the superior mesenteric artery? PMID- 1871270 TI - Some considerations for MR imaging of the liver. PMID- 1871271 TI - T1-weighted sequences for MR imaging of the liver: comparison of three techniques for single-breath, whole-volume acquisition at 1.0 and 1.5 T. AB - The authors compared three T1-weighted magnetic resonance imaging techniques that acquire images encompassing the entire liver in one breath hold. Twenty healthy volunteers were imaged--10 at 1.0 T and 10 at 1.5 T--and the results compared with those of regular short repetition time/echo time spin-echo imaging. Rapid acquisition spin echo was resistant to artifacts and had good image quality but had the lowest liver signal-to-noise (S/N) and spleen-liver signal-difference-to noise (SD/N) values. Fast low-angle shot (FLASH) had the highest S/N and SD/N, very good image quality, and only mild artifacts. TurboFLASH had good S/N and SD/N, but reduced matrix size decreased image quality. All three sequences had better SD/N than regular spin echo, and FLASH and TurboFLASH had higher S/N. On the basis of this study, the FLASH sequence appears the most attractive for T1 weighted breath-hold imaging. PMID- 1871272 TI - Normal abdominal enhancement patterns with dynamic gadolinium-enhanced MR imaging. AB - The objective of this study was to quantitatively and qualitatively determine contrast enhancement patterns of normal abdominal organs with dynamic gadolinium enhanced magnetic resonance (MR) imaging. Dynamic gadolinium-enhanced, T1 weighted, spin-echo imaging was performed during a 23-second breath hold in 38 patients, with images acquired before, during, and at 1,2, and 5 minutes after bolus injection of gadopentetate dimeglumine. Enhancement patterns of normal liver, spleen, pancreas, adrenal gland, kidney, aorta, inferior vena cava, and fat were determined by visual evaluation and by performance of signal intensity measurements with an electronic cursor. Time-intensity curves demonstrated peak enhancement of all abdominal organs during or immediately after bolus injection of gadopentetate dimeglumine. MR enhancement patterns included visualization of renal cortical nephrogram and heterogeneous enhancement of the spleen during the bolus phase of contrast material administration. Peak enhancement of normal liver was 72%; spleen, 172%; pancreas, 82%; adrenal gland, 85%; and kidney, 291%. This study established reference data regarding abdominal organ enhancement that will be useful as dynamic gadolinium-enhanced MR imaging becomes clinically implemented. PMID- 1871273 TI - Experimental hepatocellular carcinoma: MR receptor imaging. AB - Relaxation time measurements and magnetic resonance (MR) imaging were performed in three different animal models of hepatocellular carcinoma (HCC). After intravenous administration of asialoglycoprotein-directed arabinogalactan stabilized ultrasmall superparamagnetic iron oxide (10 mumol Fe/kg receptor agent), T2 of normal liver decreased from 41.6 msec +/- 1.0 to 19.4 msec +/- 1.7 (P less than .05) in rats. T2 of HCC implanted in normal liver or liver with chronic hepatitis was essentially unchanged. These results were similar to those obtained by administration of a reticuloendothelial cell-directed conventional iron oxide; however, the required dose of receptor agent was lower. MR imaging in a woodchuck model of virally induced HCC confirmed the distribution of the hepatocyte-directed agent to regions of functioning and differentiated hepatocytes but not to malignant tumor tissue. The results suggest that MR receptor imaging may play a role in the differentiation between primary liver tumor and functional liver tissue such as that in normal liver hepatitis or regenerating nodules. PMID- 1871274 TI - Preoperative segmental localization of hepatic metastases: utility of three dimensional CT during arterial portography. AB - To evaluate the accuracy of a fast three-dimensional (3D) reconstruction technique in determining the segmental location of hepatic metastases, 14 patients (40 metastases) were prospectively investigated before surgery with dynamic two-dimensional (2D) computed tomography during sequential arterial portography (CTAP). All patients underwent subsequent hepatic tumor resection within 4 days. After computer-generated mapping of hepatic venous structures with high attenuation and metastases with low attenuation, 3D reconstruction was performed. Thirty-six of the 40 lesions (90%) were detected with 2D and 3D CTAP. The accuracy in determining the segmental location of hepatic metastases was 78% (28 of the 36 metastases) for 2D CTAP and 94% (34 of the 36 metastases) for 3D CTAP. The difference in localization rates between 2D CTAP and 3D CTAP was statistically significant. The 3D CTAP technique provides vital data unattainable with other imaging modalities that improve the preoperative assessment of the resectability of hepatic metastases and allows planning a safer surgical approach. PMID- 1871275 TI - Root of the superior mesenteric artery in pancreatitis and pancreatic carcinoma: evaluation with CT. AB - To determine if changes involving the root of the superior mesenteric artery are specific for neoplasm, the authors retrospectively reviewed 173 computed tomographic (CT) examinations of patients with proved pancreatitis (103 examinations) and pancreatic ductal adenocarcinoma (70 examinations). Streaky infiltration of the fat surrounding the root was seen in 27 of 56 examinations of acute pancreatitis, in four of 24 examinations of chronic pancreatitis, in 12 of 23 examinations of pancreatitis complicated by abscess, and in 25 of 70 examinations of pancreatic carcinoma. Periarterial lymph nodes were visible in 14 with acute pancreatitis, in three with chronic pancreatitis, in six with pancreatic abscess, and in 11 with pancreatic carcinoma. A focal mass extended to within 1 cm of the root in 10 with acute pancreatitis, in two with chronic pancreatitis, in four with pancreatic abscess, and in 24 with pancreatic carcinoma; the mass obliterated the periarterial fat in seven with acute pancreatitis, in one with pancreatic abscess, and in 18 with pancreatic carcinoma. Circumferential encasement occurred in one with chronic pancreatitis, in four with pancreatic abscess, in 14 with pancreatic carcinoma, and in none with acute pancreatitis; nearly all cases of encasement revealed loss of periarterial fat. Thus, these indicators are not specific for neoplasm. PMID- 1871276 TI - Air in the portal vein: sonographic and Doppler manifestations. AB - Three patients with portal venous gas (one with radiographic and computed tomographic findings) had similar sonographic and Doppler patterns in the portal vein (PV). These patterns consisted of hyperechogenic foci moving within the lumen of the PV, producing sharp bidirectional spikes superimposed on the usual Doppler tracing of the PV. An injection of 0.25-0.50 cm3 of air, oxygen, nitrogen, and carbon dioxide into the jejunal vein of nine dogs yielded identical portal venous sonographic and Doppler patterns. In addition, the liver parenchyma of the dogs became hyperechogenic after the injection of gas. Gas in the PV is accompanied by the following signs: echogenic, moving foci within the lumen of the PV; sharp spikes on Doppler spectral display; and hyperechogenic foci within the liver parenchyma. PMID- 1871277 TI - Magnetization transfer contrast in MR imaging of the heart. AB - The use of magnetization transfer contrast (MTC) in short-echo-time (TE) cardiac magnetic resonance (MR) imaging was evaluated. For most cardiac MR imaging protocols, either long TE and short repetition time or exogenous intravascular agents are used for generating contrast between the ventricular wall and cavity as well as detecting pathologic conditions of the ventricular wall. The major problem with long-TE images is that the motion of the heart degrades the spatial resolution of the image during the TE period. However, MTC is generated by an off resonance irradiation during the interpulse delay period that is relatively insensitive to motion artifacts. Short-TE (5-15 msec) gradient-recalled echo sequences were used for imaging the heart with and without MTC. These studies revealed that MTC can be used to greatly improve the contrast between the myocardial wall and blood chamber in short-TE images and may provide useful parameters for tissue characterization in pathologic cardiac muscle. PMID- 1871278 TI - Noninvasive measurement of transmural gradients in myocardial strain with MR imaging. AB - A method is presented for performing high-resolution strain measurements by using magnetic resonance (MR) tagging. Multispectral radiofrequency pulses are used to produce tagging grids from which strain estimates are obtained with a resolution of 2 mm. A tag detection algorithm is presented that measures the center of a tag line with a precision that ranges from 0.1 to 0.2 mm over the systolic interval. With this method, a transmural gradient in the strain of a normal dog heart was detected. PMID- 1871279 TI - Right and left lung perfusion: in vitro and in vivo validation with oblique angle, velocity-encoded cine MR imaging. AB - Quantification of pulmonary flow is clinically important in the evaluation of both congenital and acquired heart disease. Velocity-encoded cine magnetic resonance (MR) is a promising technique for measuring velocity and volume of blood flow. The authors report validation of the accuracy of velocity-encoded cine MR for measurement of oblique-angle flow in vitro, with use of a constant flow phantom, and in vivo, with nine healthy volunteers in whom velocities were measured separately in the main, right, and left pulmonary arteries. Findings at MR were compared with findings at Doppler echocardiography. Velocity measurements in a flow phantom with cine MR correlated well with direct measurements at Doppler echocardiography. Velocity-encoded cine MR enabled accurate and reproducible measurement of absolute blood flow in healthy subjects. Oblique gradient flow encoding (ie, flow-encoding direction coinciding with the true direction of flow) was the method of choice for velocity measurements in the right and left pulmonary arteries. PMID- 1871280 TI - Transcatheter occlusion of pulmonary arterial circulation and collateral supply: failures, incidents, and complications. AB - Failures and complications were analyzed retrospectively in 45 patients treated with embolotherapy or occlusion of pulmonary arterial circulation. Pulmonary arterial branches were occluded with steel coils in 19 patients with pulmonary arteriovenous malformations, 17 with hemoptysis of pulmonary artery (PA) origin, and one with massive parenchymal shunt. Bronchial arterial supply to the lung was embolized with small particles in eight cases of hemoptysis and systemic to pulmonary arterial antegrade shunt secondary to chronic thromboembolism. Asymptomatic incidents included catheterization failures, vascular damage, partial occlusion, partial recanalization of the thrombus, ectopic deposition of a coil, and delayed bacterial contamination of the thrombus. A few cases of transient clinical and radiologic signs of pulmonary infarction were observed after complete occlusion of the PA and bronchial artery embolization. This complication was never observed after complete occlusion of main right or left PA, inferior right or left PA, or segmental branches. The management and prevention of these complications, the role of bronchial arterial collateral pathways, and the importance of the site of PA occlusion in the development of pulmonary infarction are discussed. PMID- 1871281 TI - Extravasation of iopamidol and iohexol during contrast-enhanced CT: report of 28 cases. AB - Extravasation of intravenously injected contrast medium is a well-known complication of radiologic procedures. Records from a 27-month period were reviewed of 28 patients in whom extravasation of nonionic contrast medium occurred during computed tomographic (CT) scanning. Extravasated amounts ranged from 3 mL in an infant to 100 mL in an adult. There were seven documented major (50-100-mL) events and nine documented moderate (10-49-mL) events. Follow-up showed that none of these patients required medical or surgical intervention as a result of extravasation. The rate of extravasation during neurologic CT scanning (head, orbits, and spine) was 0.09%, while the rate for the rest of the body (chest, abdomen, pelvis, neck) was 0.17%; the overall rate was 0.14%. The higher rate for non-neurologic studies was related to the use of a power injector. Nonionic contrast medium seemed to cause fewer systemic reactions. PMID- 1871282 TI - Clear cell sarcoma of the kidney: CT, sonographic, and pathologic correlation. AB - The sonographic and computed tomographic findings in 12 children aged 1-6 years with clear cell sarcoma of the kidney were reviewed retrospectively. Tumor size, calcification, and internal architecture were characterized and correlated with the gross pathologic findings. All tumors were unilateral and large (8.5-16 cm in diameter). Except for one, all masses were predominantly solid, and all contained some well-defined portions of low attenuation or hypoechogenicity that represented tumor necrosis. In addition, seven tumors contained uncomplicated fluid-filled cysts with diameters ranging from a few millimeters to 5 cm. Extension into the inferior vena cava was not noted. The radiologic features of clear cell sarcoma of the kidney are common to all malignant renal neoplasms. Some cases, however, may have features that simulate those of benign conditions, such as multilocular cystic nephroma or segmental cystic dysplasia. No pattern was discerned that would permit discrimination between clear cell sarcoma of the kidney and the most common renal neoplasm of childhood, Wilms tumor. PMID- 1871283 TI - Invasive cervical carcinoma: MR imaging after preoperative chemotherapy. AB - To evaluate assessment of tumor regression with magnetic resonance (MR) imaging, the authors studied 21 consecutive patients with cervical carcinoma tumors that were more than 3 cm in diameter. Thirteen of the 21 also demonstrated parametrial invasion. In all cases, MR imaging was performed both before and after chemotherapy. Pathologic specimens were obtained at hysterectomy in all patients. Comparison of pathologic and MR imaging findings after chemotherapy showed that all tumors decreased in size. Size of tumor was correctly determined at MR in 17 cases and was slightly overestimated in four cases. Five patients had residual parametrial invasion that was histologically confirmed. In detecting parametrial spread after treatment, MR imaging had an accuracy of 90.4%. Tumors had high signal intensity on T2-weighted images, whereas intratumoral necrosis was characterized by low signal intensity on the same images. Peritumoral inflammatory tissue found at pathologic examination in four of 21 cases was not specifically identified on MR images. In patients with invasive cervical carcinoma, MR imaging may be useful in evaluating tumor response to preoperative chemotherapy. PMID- 1871284 TI - Water intoxication: a complication of pelvic US in a patient with syndrome of inappropriate antidiuretic hormone secretion. AB - A woman was first seen with water intoxication caused by the voluntary ingestion of water in an attempt to fill her bladder before undergoing pelvic ultrasound (US). As in two other reported cases, this woman was receiving medication that causes the syndrome of inappropriate antidiuretic hormone secretion. A patient undergoing transabdominal pelvic US who is receiving these medications and whose bladder is not full should undergo examination by means of a transvaginal or endorectal route. PMID- 1871285 TI - Calcaneal insufficiency avulsion fractures in patients with diabetes mellitus. AB - Radiographs and clinical records of 61 patients with calcaneal fractures were studied. Twenty-one patients had diabetes mellitus, and 40 were nondiabetic. All diabetic patients were insulin dependent for more than 5 years and had clinically evident peripheral neuropathy. Eighteen of the diabetic patients had no history of significant trauma. Fourteen had calcaneal insufficiency avulsion (CIA) fractures limited to the posterior third of the calcaneus. The fracture pattern in this group occurred in the same plane as a fatigue-type calcaneal fracture. Fragments of the posterior tuberosity were usually displaced 10-30 mm and were frequently rotated. The mean time from diagnosis of diabetes mellitus to CIA fracture was 20 years. Fractures in the nondiabetic group and in the three diabetic patients with a history of trauma did not resemble the CIA pattern. In the nondiabetic group, there were no insufficiency fractures; 39 fractures occurred with significant force (eg, motor vehicle accident or fall from height), and 33 had extension to subtalar or calcaneocuboid joints. PMID- 1871286 TI - Lateral tibial rim (Segond) fractures: MR imaging characteristics. AB - The magnetic resonance (MR) imaging characteristics of lateral tibial rim (Segond) fractures and their associated injuries were reviewed in 12 patients with radiographic evidence of this fracture. Bone marrow adjacent to the fracture emitted a focally abnormal MR signal, which indicated an injury of the lateral capsular junction. The Segond fragment, however, was seen on MR images in only four of 12 patients. Associated ligamentous and meniscal injuries identified with MR imaging and arthroscopy involved the anterior (n = 11) and medial (n = 7) cruciate ligaments and the lateral (n = 4) and medial (n = 1) menisci. Focal bone marrow edema was due to injury of the lateral capsular junction. MR imaging evidence of such edema should indicate the presence of a lateral capsular injury and fracture, if one has not already been demonstrated with conventional radiography. A high association of Segond fractures with tears of the anterior cruciate ligament was confirmed, and MR imaging signs of a Segond fracture may therefore be used as indirect evidence for tears of that ligament. PMID- 1871287 TI - Normal rotator cuff: MR imaging with conventional and fat-suppression techniques. AB - The signal intensity and morphologic characteristics of the rotator cuff and surrounding structures at magnetic resonance (MR) imaging were investigated with five pulse sequences in 15 asymptomatic subjects. In all subjects, a focal region of relative increased signal intensity corresponding to the critical zone was observed in the supraspinatus tendon just proximal to its insertion. Soft-tissue signal intensity (isointense with muscle) was also located between the supraspinatus tendon and underlying joint capsule, interposed between the conjoined leaves of the supraspinatus and infraspinatus tendons, and superolateral to the conjoined cuff tendon, near its insertion. These regions were most conspicuous and most clearly defined with fat-suppression imaging. Small amounts of fluid were observed within the joint space and its recesses, the bicipital tendon sheath, and the subacromial-subdeltoid bursa. These and other MR imaging findings of this study previously have been regarded as indicative of rotator cuff abnormalities. These results will help refine the criteria for diagnosis of rotator cuff disorders with MR imaging. PMID- 1871288 TI - Postoperative bone marrow alterations: potential pitfalls in the diagnosis of osteomyelitis with In-111-labeled leukocyte scintigraphy. AB - Scintigraphy was used after injection of technetium-99m methylene diphosphonate (MDP) and indium-111-labeled white blood cells (WBCs) to assess for the presence of osteomyelitis in 97 patients who had undergone prior surgical procedures. Thirty-four patients with abnormal In-111-labeled WBC patterns underwent restudy with Tc-99m albumin colloid (AC). Scintigraphic findings were considered positive for osteomyelitis whenever localization of In-111-labeled WBCs exceeded Tc-99m AC activity in extent or focal intensity (discordant pattern). Ten of 12 patients with culture-proved osteomyelitis had discordant patterns; two had false-negative (concordant) patterns. The cases of 20 of 22 patients without infection who were considered to have osteomyelitis on the basis of patterns of In-111-labeled WBCs and Tc-99m MDP were reclassified correctly on the basis of concordant patterns of In-111-labeled WBCs and Tc-99m AC. Radiocolloid images improved the overall scintigraphic specificity for osteomyelitis from 59% without bone marrow imaging to 92%; sensitivity decreased from 94% to 88%. PMID- 1871289 TI - Temporomandibular joint after meniscoplasty: appearance at MR imaging. AB - Twenty-five temporomandibular joints (TMJs) were studied in 20 patients who had undergone meniscoplasty. In all patients, preoperative magnetic resonance (MR) images showed anteriorly dislocated disks; all patients underwent a similar postoperative MR examination an average of 6 months after surgery. The results of these studies were correlated with clinical results of surgery, which were classified as poor, fair, good, or excellent at follow-up MR imaging. In 10 TMJs (eight patients [40%]) the clinical results were excellent or good; in 15 TMJs (12 patients [60%]), fair or poor. The position of the disk relative to its preoperative position was a good discriminator in determination of the clinical success of meniscoplasty. After surgery, in all patients with good or excellent results, the disks appeared to be in a normal or an improved position compared with that prior to surgery; in those with poor or fair results, the TMJs had anteriorly dislocated disks that showed no improvement. PMID- 1871290 TI - Simulated aggressive skull base erosion in response to benign sinonasal disease. AB - Benign sinonasal masses and slow-growing neoplasms tend to remodel the nasal vault and facial bones, and this is particularly true of nasal polyps and inverted papillomas. However, when such benign masses press against the floor of the anterior cranial fossa and the walls of the sphenoid sinuses, simulated aggressive bone destruction rather than bone remodeling usually occurs. This type of bone destruction implies to the radiologist that a carcinoma may also be present, and this information could dissuade a surgeon from operating with an attempt at cure. In fact, about 90% of the time with inverted papillomas and in virtually all cases of nasal polyposis, no carcinoma is present. The computed tomographic (CT) scans and magnetic resonance images of 14 patients are used to demonstrate these changes. In addition, the CT scans of three patients with malignancies are shown to illustrate the similarity in the bony skull base changes. PMID- 1871291 TI - Hemangioma of the nasal vault: MR and CT features. AB - Six patients with a history of epistaxis (five patients) or nasal obstruction (one patient) were found to have a capillary hemangioma of the nasal vault that involved one or more nasal turbinates. Four patients underwent computed tomographic (CT) examination; two of these also underwent magnetic resonance (MR) imaging. Four others underwent only MR imaging. At CT and MR, all of the lesions were well circumscribed and intensely enhancing, with contralateral deviation of the nasal septum. Remodeling of the surrounding bone was present in three patients. On T1-weighted MR images, the masses were intermediate in signal intensity. Varying degrees of T2 shortening were shown on T2-weighted MR images, with an appearance that suggested the presence of blood products surrounding an inner matrix of higher-signal-intensity tumor. Intense enhancement at CT and MR assisted differentiation of tumor from retained sinonasal secretions. In two patients, external carotid arteriography revealed small foci of pooling contrast material; in one of these patients, arteriovenous shunting was also present. Pathologic examination in all patients demonstrated capillary hemangiomas with varying degrees of fibrosis and hemosiderin deposition. PMID- 1871292 TI - Importance of daily rounds by the radiologist after interventional procedures of the abdomen and chest. AB - A prospective study was performed to evaluate the clinical utility of daily rounds by the radiologist for patients with indwelling catheters in the chest and abdomen, placed during interventional radiologic procedures. The 7-week evaluation included documentation of the number of patients seen, time spent with each per day, number of problems identified, management of these problems, and consultations for new cases generated by interaction with other staff. During the 268 visits to 37 patients, 59 catheter-related problems were identified; 17 (29%) required further intervention in the radiology department, and 42 (71%) were managed at the patient's bedside. Of the patients who were followed up, 22 (59%) had some catheter-related problem identified during their hospital stay. Daily rounds by the radiologist are an essential component of patient care after catheter-related interventional procedures and should be made by those who perform and understand the procedures. PMID- 1871294 TI - Persistent nidus blood flow in cerebral arteriovenous malformation after stereotactic radiosurgery: MR imaging assessment. AB - Stereotactic radiosurgery has become a major force in the treatment of arteriovenous malformations (AVMs) of the brain. After treatment, obliteration of flow through the malformation occurs in 75%-85% of cases within 2 years, assuming the entire AVM nidus can be encompassed by the radiation field. Because the follow-up period is relatively long, a noninvasive means to assess residual transnidus blood flow is desirable. The authors report favorable findings after a comparative analysis of 85 posttreatment magnetic resonance images and 27 follow up cerebral arteriograms in 34 patients treated with stereotactic radiosurgery. The authors found that transnidus flow can be determined from apparent signal intensity differences between tandem two-dimensional gradient-recalled echo images obtained first without and then with gradient moment nulling (flow compensation), with empirically derived pulse parameters. This method provides a means to monitor the reduction in AVM matrix size and to assess the extent of persistent arteriovenous shunting (ie, blood flow) across the nidus. PMID- 1871293 TI - Pituitary adenoma: correlation of half-dose gadolinium-enhanced MR imaging with surgical findings in 26 patients. AB - Sellar magnetic resonance imaging studies obtained with half doses of gadopentetate dimeglumine (0.05 mmol/kg) were prospectively interpreted and retrospectively rated in 26 patients who subsequently underwent transsphenoidal sellar surgery for suspected pituitary adenoma. Studies included a sagittal scout view followed by a non-contrast-material-enhanced, an immediate postcontrast, and a delayed postcontrast T1-weighted image (obtained at 1.0 or 1.5 T). Ten of 11 confirmed microadenomas were identified prospectively; all were identifiable in retrospect. Macroadenomas (12 cases) were well demonstrated. The high signal intensity of the posterior pituitary and of intrasellar hemorrhage was obscured on postcontrast studies. Delayed images proved unnecessary. This prospective evaluation suggests that a half-dose study is comparable to retrospective studies in which full-dose techniques were used for detection of micro- and macroadenomas. Imaging times are reasonably short, and cost of contrast material is potentially reduced. Confirmation with larger studies is required, and careful endocrinologic and clinical follow-up of nonsurgical patients is necessary. PMID- 1871295 TI - Membranous lipodystrophy: MR imaging appearance of the brain. AB - Five patients with membranous lipodystrophy (lipomembranous polycystic osteodysplasia with progressive dementia) underwent magnetic resonance (MR) imaging of the brain. T2-weighted MR images showed atrophied cerebral white matter with dilated ventricles; increased signal intensity of the white matter; and decreased signal intensity of the thalamus, putamen, caudate nucleus, and cerebral cortex. Although each single finding is not specific, the combination of the above MR findings when coupled with skeletal lesions strongly suggests this rare disease. PMID- 1871296 TI - Fetal cisterna magna septa: a normal anatomic finding. AB - A linear hyperechoic structure in the cisterna magna, previously described as the straight sinus, was investigated during routine obstetric ultrasound (US) examination. One hundred three fetal US examinations were performed to determine the prevalence and appearance of this finding. Also, US water-bath examination of 18 fixed postmortem specimens and fetuses was performed, and results were correlated with those of gross and microscopic examination of the fetal brain. The structure was identified in 95 (92%) prenatal examinations between 15 and 38 menstrual weeks. It was located posteriorly between the cerebellar hemispheres in the cisterna magna. In those 95 cases in which it was identified, it appeared as a single echogenic line in 31 cases (33%), as two echogenic lines in 47 (49%), or as three or more lines in 17 (18%). When two echogenic lines were identified, they appeared "cystlike" in 17 (18%) of the 95 examinations. Correlation of the gross and histologic findings demonstrated these lines to represent normal subarachnoid septa rather than the straight sinus. PMID- 1871297 TI - Fetal cephaloceles: diagnosis with US. AB - The prenatal sonograms of 15 fetuses with cephaloceles (13 occipital, one ethmoidal, and one frontoparietal) were retrospectively reviewed. The prognosis for fetuses with cephaloceles was poor: Only three of 14 with follow-up were born alive (21%), and all are likely to be handicapped. Karyotypes were abnormal in four of nine fetuses tested (44%). Associated cranial abnormalities observed in various numbers of fetuses included ventriculomegaly, the "lemon" sign, a flat basioccipital, "beaked" tectum, and bone defect. A wide variety of neural and nonneural anomalies were associated with cephaloceles. At least one sonographically observed concomitant neural or nonneural axis abnormality or an abnormal karyotype was present in nine of 15 fetuses (60%). Some associated neural malformations noted pathologically were not observed prenatally. Cranial meningoceles were not accurately distinguished from encephaloceles sonographically, and they also were associated with a poor prognosis. Comparison of findings in fetuses with cephaloceles with those of 15 fetuses with cystic hygromas revealed that the two abnormalities can usually be distinguished by the relationship of the mass with the neck and by other cranial findings present in fetuses with cephaloceles but absent in association with cystic hygromas. PMID- 1871298 TI - Epiphyseal marrow in infancy: MR imaging. AB - Hypointense epiphyseal marrow on T1-weighted magnetic resonance images often suggests disease. To determine whether hypointense marrow sometimes represents normal red marrow in a recently ossified epiphyseal center, the authors studied 38 infants without known marrow disease. Patients with hypointense epiphyseal marrow on T1-weighted images were younger (3.9 months +/- 3.2) than those with hyperintense marrow (9.6 months +/- 3.9) (P less than .001). T1-weighted imaging and histologic correlation were also performed in animals. The signal was hypointense and the marrow was red in the epiphyseal centers of all newborn animals, while all 6-week-old animals had hyperintense signal and yellow marrow. The authors conclude that hypointense marrow on T1-weighted images represents normal red marrow in a recently formed ossification center in newborn rabbits and lambs, and the same is probably true in humans. Epiphyseal marrow becomes hyperintense within a few months of development of the secondary center of ossification. PMID- 1871299 TI - Epiphyseal involvement in osteosarcoma. AB - Plain radiography and magnetic resonance (MR) imaging were used to assess the extent of transphyseal involvement in 15 consecutive patients with long bone osteosarcoma and nonfused epiphyses. The findings were correlated with those from surgical and microscopic pathologic examinations. There were no cases of false positive findings with either MR imaging or plain radiography. Conventional radiography accurately helped predict transphyseal spread in only nine of 15 cases (60%). Spread to the epiphysis was present in 12 of the 15 cases (80%) and was accurately predicted with MR imaging in all 12 cases. This finding contradicts the common misconception that the physis acts as a "barrier" to tumor spread. PMID- 1871300 TI - Pulmonary sequestration: diagnosis with color Doppler sonography and a new theory of associated hydrothorax. AB - The diagnosis of pulmonary sequestration has traditionally relied on angiographic demonstration of a systemic artery to the sequestered lung tissue. Rarely, extralobar sequestration can be associated with tension hydrothorax, which in the past has invariably led to fetal hydrops and death. The authors report the cases of three infants who had initially undergone color and spectral Doppler analysis; in two of them, extralobar sequestrations were associated with congenital hydrothorax. All three patients underwent surgical resection and histopathologic evaluation of their sequestrations. On the basis of the findings, the authors believe that torsion of the sequestration occludes the efferent venous and lymphatic channels, initiating the accumulation of pleural fluid and subsequent hydrops through systemic venous obstruction. Color Doppler made possible the identification of minute feeding vessels, obviating further diagnostic studies. PMID- 1871301 TI - Socioeconomic and political issues in radiology: a historical analysis. AB - Radiology literature indexes were searched for articles concerning socioeconomic and political issues published during two 21-year periods: 1920-1940 and 1970 1990. Of 200 articles found, 96 were considered appropriate for study, 40 from 1920-1940 and 56 from 1970-1990. All except two of the articles were from Radiology or the American Journal of Roentgenology. The articles were organized into 16 categories. By quantifying the number of times these socioeconomic and political issues appeared and comparing quotations from the articles, the authors demonstrated many common issues in the two periods, despite drastic differences in radiology practice. Analysis of historical literature provides perspective on current socioeconomic and political issues and may help formulate solutions to current problems. Documentation of such issues facilitates historical analysis and is an important function of the radiology literature. PMID- 1871302 TI - Usefulness of mammography and sonography in women less than 35 years of age. AB - Indications, clinical history, mammographic findings, and clinical outcome were reviewed in 1,016 women younger than 35 years who underwent mammography during an 8-year period. The indications for mammography were a palpable mass in 454 (44.7%), findings at routine screening in 237 (23.3%), lumpiness in 29 (14.9%), unilateral nipple discharge in seven (3.5%), localized breast tenderness in six (5.1%), adenopathy in three (1.9%), diffuse tenderness in two (2.9%), bilateral nipple discharge in two (1.5%), and miscellaneous in four (2.2%). In 405 women (39.9%), at least two-thirds of the breast tissue was radiodense; however, in 299 (29.4%) women the breast was predominantly fatty, allowing for excellent mammograms. Six women had carcinomas: Mammographic findings prompted biopsy in one patient, indicated a benign-appearing mass (found to be solid at sonography or aspiration) in three patients with a palpable mass (contributing to delay in biopsy in two), and were negative in two. Sonography was performed in 389 women and was useful in preventing unnecessary biopsy of cysts but was not useful in differentiating benign from malignant solid masses. Younger women with persistent localized breast symptoms should undergo a tailored mammographic examination, but negative findings or findings of a benign lesion should not preclude biopsy of a palpable solid mass. PMID- 1871303 TI - Steatocystoma multiplex: appearance at mammography. AB - The authors present mammographic findings in a patient with steatocystoma multiplex. Numerous oil cysts were seen in both breasts at mammography. The mammographic appearance is characteristic of, if not pathognomonic for, steatocystoma multiplex. PMID- 1871304 TI - Anatomy of the major fissure: evaluation with standard and thin-section CT. AB - The major fissures of the right and left lungs were studied with standard computed tomography (CT) (10-mm-thick sections) and thin-section CT (2-mm-thick sections) in 50 patients. On standard CT scans, the major fissures were seen in 90%-100% of cases at each of three selected levels. They usually appeared as hypoattenuating bands and less often as lines or hyperattenuating bands. Although in most cases the major fissure was seen as a line on thin-section CT scans, this appearance was more common in the upper portion of the left major fissure than in the upper portion of the right major fissure. A "double-fissure sign" was most frequently seen at the base of the left lung; however, the sign was also seen at higher levels, with approximately equal frequency in the right and left lungs. An incomplete major fissure was noted in the right lung in 32 cases (64%) and in the left lung in 26 cases (52%). The upper and middle portions of the left major fissure were less frequently incomplete than were the comparable portions of the right major fissure. Thin-section CT provided better delineation of the major interlobar fissures than did standard CT. PMID- 1871305 TI - Lung parenchyma: magnetic susceptibility in MR imaging. AB - Magnetic susceptibility effects in magnetic resonance (MR) imaging of normal lung parenchyma occur because of magnetic-field inhomogeneities induced by the microscopic heterogeneity of the lung. The effects on MR imaging of the lung are loss of signal from intravoxel phase dispersion (measured with T2') and a shift in the macroscopic resonant frequency from that of water toward that of air (delta v). These effects of MR imaging at 1.5 T were quantitated by measuring T2' decay and delta v at different locations in the lungs of two adult volunteers and one excised inflated human lung. The average T2' was 7 msec in the excised inflated specimen and 6.3 msec in normal in vivo lungs. There was a gravitational increase in T2' from nondependent to dependent lung. T2' increased to 35 msec in atelectatic lung tissue and to more than 140 msec in tumor. The macroscopic resonant lung frequency increased to 3.6 ppm more than that of mediastinal muscle. These values are important for developing MR pulse sequences appropriate for imaging lung parenchyma. PMID- 1871306 TI - Small object contrast in AMBER and conventional chest radiography. AB - The ability of a commercially available scanning equalization system for chest radiography to render small object contrast in the lung-, mediastinum-, and subdiaphragm-equivalent regions of an acrylic chest phantom was quantitatively evaluated. Images from nine chest phantoms that represented a wide range of patient sizes and dynamic ranges of x-ray transmittance were analyzed. Subject contrast was measured with a photostimulable phosphor detector, and images were acquired in both equalized and nonequalized (conventional) imaging modes. Available subject contrast in the lung-equivalent region was 8%-15% lower in the equalized images compared with the nonequalized images in all phantoms (patient types); contrast in the mediastinum-, retro-cardiac-, and subdiaphragm-equivalent regions was 11%-63% higher in the equalized images, with the degree of improvement increasing as patient size and dynamic range increased. Images of each phantom were also acquired with the screen-film systems currently in use at the authors' institution, permitting an assessment of the relative performance (in terms of radiographic contrast) of these imagers with and without use of equalization. PMID- 1871307 TI - Radiation exposure to angiographers under different fluoroscopic imaging conditions. AB - Radiation levels near an imaging chain commonly used in angiography were measured with both a 100- and a 200-mm-thick scatter phantom. The scatter was measured in lines parallel in space to the central ray of the x-ray beam, at lateral distances of 300, 500, and 800 mm. The effects of fluoroscopic kilovoltage and image intensifier magnification mode were also measured. The results indicate that the highest scattered radiation levels occur near the surface of the patient where the x-ray beam enters. Exposure rates were measured in both anteroposterior (AP) and posteroanterior (PA) geometries on a U-arm system. In PA geometry, the highest radiation levels occur below the angiographer's waist, an area well protected by the lead apron. The AP geometry increases the exposure rate to the neck, head, and upper extremities, areas where apron shielding is less effective. PMID- 1871308 TI - Medulloblastoma: long-term follow-up of patients treated with electron irradiation of the spinal field. AB - Thirty-two patients with posterior fossa medulloblastoma underwent treatment with electron irradiation to the spinal field. The 5- and 10-year actuarial survival rates were 57% and 50%, respectively. Late complications observed in the 15 patients followed up for more than 5 years were short stature (six patients), decreased sitting-standing height ratio (four patients), scoliosis (two patients), poor school performance (seven patients), xerostomia (one patient), esophageal stricture (one patient), pituitary dysfunction (four patients), primary hypothyroidism (one patient), bilateral eighth-nerve deafness (one patient), and carcinoma of the thyroid (one patient). Complications following treatment with electrons to a spinal field are compared with reported complications following treatment with photons to the spinal field. Although short-term reactions were minimal, the authors found no difference in late complications. More sophisticated treatment planning may show such a long-term benefit in the future. PMID- 1871309 TI - James Picker (1882-1963): lest we forget! PMID- 1871310 TI - Paraffin block radiography following breast biopsies: use of orthogonal views. AB - Paraffin block radiography has been shown to be useful in helping identify lesions in biopsy specimens of breast tissue. Use of an orthogonal view enables determination of the approximate depth of a lesion within a paraffin block. This simple technique further guarantees histologic evaluation of the area of radiographic concern. PMID- 1871311 TI - Selective spinal panangiography: use of a 4-F braided catheter with a soft-tip configuration. AB - A 4-F braided catheter with a soft radiopaque tip was used in selective spinal panangiographic procedures. Results obtained with the catheter were compared with those obtained in procedures with conventional catheters. The catheter was used in the intercostal, lumbar, and sacral arteries. Advantages of using this catheter include excellent maneuverability, reduced patient exposure to contrast medium, and reduced fluoroscopy duration. PMID- 1871312 TI - Use of an acoustic transponder for US visualization of biopsy needles. AB - A 20-gauge Chiba needle with a stylet embedded with polyvinyldifluoride (PVDF), a polymer that acts as an acoustic-electric transducer, facilitated a variety of diagnostic and therapeutic ultrasound (US)-guided interventions in nine patients. PVDF receives acoustic energy from the US scanner and transmits an electrical signal through the stylet and a shielded cable to the scanner, which results in appearance of a bright echo on the monitor at the location of the needle tip. PMID- 1871313 TI - Reference to dorsal intercalated segment instability in the literature. PMID- 1871314 TI - Value of sonography in acute encephalomalacia. PMID- 1871315 TI - The synthesis and structure of comovirus capsids. PMID- 1871316 TI - Molecular mechanisms involved in the regulation of amino acid transport. PMID- 1871317 TI - Fractal and chaotic dynamics in nervous systems. AB - The chaotic aspects of brain structure and dynamics have been discussed. The relation of chaos to fractal processes in the brain from the neurosystems level down to the molecule has been explored. It is found that chaos appears to play an integral, though not necessarily exclusive role in function at all levels of organization from the neurosystems to the molecular and quantum levels. An interesting consequence involving the possible interface between chaotic dynamics and quantum physics has been discussed because of its potential significance is resolving several of the most intractable conceptual problems to do with computability, the brain and the mind (Blakemore and Greenfield, 1987; Hooper and Teresi, 1987; Rose, 1973; Searle, 1979; Penrose, 1986, 1989). PMID- 1871318 TI - The modular cerebellum. PMID- 1871319 TI - Nerve growth factor and the neostriatum. AB - 1. The present review summarizes evidence describing the expression, immunoreactivity, binding, transport, development, aging, and functions of NGF in the mammalian neostriatum. 2. Neostriatal NGF binding sites and intrinsic cholinergic neurons are co-localized, increase at a similar rate during ontogeny, and are lost to an equal extent following age- or injury-induced loss of neostriatal neurons. 3. Exogenously administered NGF augments ChAT activity in the intact caudate-putamen, nucleus accumbens, and following mechanical or excitotoxin-induced cholinergic injury. NGF antibodies lower ChAT in the intact caudate-putamen. 4. Neostriatal cholinergic interneurons are lost in the aged rat but also in Alzheimer's disease, Parkinson's disease, supranuclear palsy, and Huntington's chorea. Future studies need to address the extent to which these losses result from an abbreviation of NGF production, binding, or transport and whether rhNGF administration may retard or reverse these cholinergic losses. PMID- 1871320 TI - Integrated genetic databases in the study of neuropsychiatric diseases: inborn errors of cerebral metabolic pathways? AB - 1. Genetic databases are an expanding and readily accessible repository of information on the mapping and sequencing of the human genome, and that of other model organisms. The integration and application of this information to neuropsychiatric disease is illustrated using neuroendocrine and neuropharmacologic data, computerized and other genetic databases. 2. This computer-assisted integrated approach to knowledge structures permits the rapid generation of hypotheses, the prompt identification of candidate gene loci, an explanation for genetic heterogeneity, and strategies for the use of potential linked markers. 3. Results using this integrated search strategy demonstrate that over 30 candidate loci for neuropsychiatric disease have currently been mapped in man (spread over 14 chromosomes in the human genome), and that at least 6 homologous loci have been mapped in mouse. 4. Using a metabolic pathway approach, it can be shown that the best current candidate gene locus for a subtype of schizophrenia located on chromosome 5q11-13 (HGML10 # SCZD1 and OMIM #181510) is in the serotonergic pathway, i.e. a receptor for 5-hydroxytryptamine (subtype 1A; HGML10 #HTR1A) which also maps in the same chromosomal region. 5. Parallels are suggested between inborn errors of metabolic pathways in the somatic endocrine system (using insulin-dependent diabetes mellitus as a paradigm) and the neurotransmitter and hormonal systems within the brain. 6. A subset of neuropsychiatric disorders may thus be viewed as inborn errors of cerebral metabolic pathways primarily affecting the biogenic amine pathways. PMID- 1871321 TI - New vistas on 5-HT receptors and migraine. AB - 1. A number of serotonergic agents have been shown to be effective in the treatment of migraine. At the present time, migraine drug interactions have been analyzed most extensively at 5-hydroxytryptamine1D (5-HT1D), 5-HT2 and 5-HT3 receptor subtypes. 2. This review will summarize the current status of 5-HT receptor subtypes as they relate to anti-migraine agents. 3. The available data suggest that drug interactions with specific 5-HT receptor subtypes may be the basis for their efficacy in both the acute and prophylactic treatment of migraine. PMID- 1871322 TI - Animal models of depression reflect changing views on the essence and etiology of depressive disorders in humans. AB - 1. Since it is ethically unacceptable to use human subjects to conduct manipulative experimental hypothesis-testing research on major depression, investigators interested in the development, the substrates or the mechanisms of treatment of depressive disorders have turned to observational models with humans or to interactive models with animals. 2. One of the earliest animal models of depression, the infant/mother separation in monkeys, is based on the Freudian notion of the loss-inward directed anger-depression connection. 3. The hypothesis that depression is caused by stress led to the development of numerous animal models of depression based on the behavioral abnormalities induced in animals, usually rats but occasionally other species, by exposure to prolonged or intense stress. 4. The selective therapeutic efficacy of antidepressant drugs suggested the hypothesis that depression is caused by a neurochemical abnormality that is alleviated by chronic exposure to antidepressants. This hypothesis has been refined to state that depressive disorders are caused by genetically based neurochemical dysregulation of neural activity in the limbic system. 5. Models based on the limbic dysfunction hypothesis could be used to explore the specific neural substrates of depression. At present, the rat with limbic dysfunction induced by olfactory bulbectomy appears to fulfill best the requirements for a model of depression. The future development or discovery of a genetic strain of animals that shows comparable behavioral and neurovegetative deficits and similar selective drug responses to those seen in patients with depressive disorder, would make tremendous contributions to the understanding not only of depression but also of the neurobiology of the limbic system. PMID- 1871323 TI - Extensive and enantioselective presystemic metabolism of dl-threo-methylphenidate in humans. AB - 1. Two pilot studies were carried out to investigate the enantioselective pharmacokinetics of methylphenidate (MPH) in children with attention deficit hyperactivity disorder (ADHD). A more definitive study, which included administration of an intravenous dose, was carried out in healthy young men. 2. Serial plasma samples were harvested from predose to 8 hours in the first pilot study, predose to 12 hours in the second pilot study and predose to 16 hours in the definitive study. Plasma levels of the separate isomers d-MPH and 1-MPH were determined by an enantioselective gas chromatographic method. 3. In the first pilot study, 6 boys with ADHD each received his regular dose of MPH (10mg n = 5, 5mg n = 1), which contained equal proportions of d-MPH and 1-MPH in an immediate release formulation (MPH-IR). No MPH was detectable in the predose plasma. Thereafter, plasma levels of the more active d-MPH were 4 to 10 fold higher than those of 1-MPH. Plasma levels of 1-MPH were so low that it was not possible to monitor them beyond 4 hours in some children. 4. In the second pilot study, 5 boys and 1 girl with ADHD each received their regular dose (20mg) of a slow release formulation (MPH-SR). No MPH was detectable in the predose plasma. Thereafter, plasma levels of the more active d-MPH were 5 to 10 fold higher than those of 1-MPH. It was possible to monitor plasma levels of 1-MPH over the full 12 hour period of study in 5 of the 6 children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871324 TI - Deuterium-labelled p-tyramine challenge test and phenolsulfotransferase activity in depressed patients--failure to replicate decreased p-tyramine conjugation in depression. AB - 1. Depressed and normal subjects were challenged with deuterium-labelled p tyramine and urine was collected for 3 h. 2. Urinary excretion of conjugated p tyramine was not significantly different between normal, melancholic and non melancholic depressed subjects. 3. Platelet phenolsulfotransferase activity to p tyramine (p less than 0.05) and to phenol (p less than 0.005) were significantly lower in the depressed patients. PMID- 1871325 TI - Temporal segmentation of response speed in depression: neuro-electrophysiological approaches. AB - 1. Depressive psychomotor retardation, as observed by delayed reaction times (RT), may be related to a slowing in information processing speed. 2. Two separate studies compared indices of information processing speed in depressed patients and non-clinical controls by segmenting behavioral RT with brain event related potentials (ERPs) and electromyographic (EMG) responses. 3. In Study I, slower behavioral RTs in depression were concomitant with slower central processing times (CPT) but not motor execution times (MET). 4. In Study II, P165, a putative early cognitive ERP related to 'stimulus evaluation time', was found to be slower but within normal range in depressed patients. PMID- 1871326 TI - Preparatory brain potentials in major depressive disorder. AB - 1. Psychomotor slowing in depression is frequently reflected by delayed reaction times (RT). 2. The role of central arousal mechanisms in response slowing was examined by comparing scalp-recorded slow negative potentials of depressed patients with normal controls in two separate studies. 3. Varying fore-warned RT conditions elicited contingent negative variation (CNV) waveforms and the resultant mid-point amplitudes of these waveforms together with orienting (O wave), expectancy (E-wave) and post-imperative negative variation (PINV) component amplitudes and sensory evoked responses (N1, P2) were compared between groups. 4. RTs were significantly slowed in depressed patients and the patient group exhibited consistently larger PINV amplitudes. Depending on the RT condition, patients also exhibited larger mid-point CNV amplitudes and smaller N1 and P2 amplitudes. PMID- 1871327 TI - The effect of methyltestosterone on the growth hormone response to the dopamine receptor agonist, apomorphine. AB - 1. There is some evidence that androgens affect dopaminergic function in animals and man. We investigated the effect of methyltestosterone (MT) (30 mg po) on the growth hormone (GH) response to the dopamine (DA) receptor agonist, apomorphine (Apo) HC1 (0.5 mg sc), in 9 normal men. MT was given 2 hr before Apo. 2. The peak plasma MT concentration was present 1 hr after administration (19.9 +/- 19.5 ng/ml; X +/- SD); the concentration at 4 hr was 7.2 +/- 4.9 ng/ml. At the time of Apo administration, plasma MT varied from 6.0-24.1 ng/ml. 3. There was no significant effect of MT on Apo-GH secretion (interaction F(7,56) = 1.08; p = NS). The mean individual peak GH concentration after Apo alone was 20.2 +/- 11.9 (X +/- SD) vs 22.2 +/- 9.9 ng/ml when MT preceded Apo (p = NS). 4. These results suggest that exogenous androgens do not affect DA receptor function in males with normal androgenic function. Lack of effect due to an insufficient dose or duration of administration of MT cannot be excluded. PMID- 1871328 TI - Haloperidol reductase activity in red blood cells from oriental patients on haloperidol. AB - 1. We measured haloperidol reductase activity in red blood cells in 87 samples collected from 50 Japanese psychiatric patients on HAL. HAL reductase activities in the patients were in a range of 7.9-26.1 pmol/hr/10(6) RBC (mean = 13.4, S.D. = 3.4). Interindividual variability was as large as 25.4% (CVs), while intraindividual CVs were small (8.9%). 2. Distribution of HAL reductase activities was normal but their values were slightly lower in the patients than those in the normal controls, though the difference between these two groups was not significant. 3. No significant correlations were found between HAL reductase activity in RBC vs dose of HAL per body weight, or plasma and RBC RHAL/HAL ratio. PMID- 1871329 TI - Involvement of M1 and M2 muscarinic receptors of the basal forebrain in cholinergically mediated changes in the rat locomotion. AB - 1. Wistar rats were implanted with cannulae into the medial preoptic and anterior hypothalamic areas for intracerebral injections. 2. Unilateral intracerebral injections of carbachol (1 microgram) into a limited area of the basal forebrain decreased significantly both the distance travelled by the animals and time spent walking. 3. In addition to the decrease in locomotion, it was demonstrated for the first time that injections of carbachol also slow animal movement by significantly decreasing speed of forward progression. 4. All locomotor effects of carbachol were reversed by local pretreatment with atropine (1 microgram) but not by pirenzepine (2 micrograms) suggesting that these effects were mediated by M2 muscarinic receptors with minimal or no M1 receptor involvement. PMID- 1871330 TI - Metabolism of antidepressants: urinary metabolites of trimipramine in the rat. AB - 1. Studies on the metabolism of the tricyclic antidepressant trimipramine (TMP) in the rat are described. 2. Twenty metabolites of TMP were isolated from rat urine after enzymatic hydrolysis and their structures were determined by a gas chromatographic-mass spectrometric (GC-MS) method. 3. Twelve TMP metabolites were the result of alicyclic (C10 or C11) oxidation in addition to the other metabolic pathways. PMID- 1871331 TI - Localization of cholecystokinin binding sites in canine brain using quantitative autoradiography. AB - 1. CCK receptors have been characterized and localized in various mammalian species and significant species-specific differences in their distribution have been identified. In the present study, we report the first autoradiographic localization of CCK binding sites in the canine brain. 2. High densities of [125I]BH-CCK-8 binding sites were found in the cortex, cerebellum, hippocampus, caudate nucleus, olfactory bulb and nucleus accumbens. Moderate densities were present in the putamen, amygdala, and substantia gelatinosa. Low binding densities were observed in the globus pallidus, inferior colliculus, hypothalamus and thalamus. 3. Although the distribution profile of CCK binding sites in canine brain is similar to those previously reported in the rodent, primate and human brain, notable differences were observed in the hippocampus, cortex and cerebellum. PMID- 1871332 TI - Studies on the properties of some peripheral MAO inhibitors. AB - 1. Studies were carried out on three monoamine oxidase (MAO) inhibitors, two of which, debrisoquine and para- hydroxyphenelzine, are purported to be peripheral inhibitors and one, phenelzine, is a peripherally acting inhibitor, which has been included for comparitive purposes. 2. All three showed varying degrees of specificity towards MAO type A. 3. The action of debrisoquine was very rapid as was that of para- hydroxyphenelzine. 4. The inhibition caused by debrisoquine was competitive and reversible, while that caused by both phenelzine and para- hydroxyphenelzine was irreversible. 5. The inhibition caused by debrisoquine appeared to be unaffected by the pH of the medium. PMID- 1871333 TI - Enzymatic N-methylation of phenelzine catalyzed by phenylethanolamine N methyltransferase. AB - 1. Phenelzine has been found to be methylated by enzymes obtained from bovine adrenal and some rat tissues in the presence of S-adenosylmethionine (SAM) as methyl group donor. 2. The methylated product was chromatographically (TLC and HPLC) identical with chemically synthesized N-methylphenelzine. The structure of this methylated phenelzine has been confirmed by a GC-MS procedure. 3. The phenelzine methyltransferase in the bovine adrenal has a molecular weight and isoelectric point identical with that of bovine adrenal phenylethanolamine N methyl-transferase (PNMT). 4. Methylated phenelzine possesses much reduced inhibitory activity towards monoamine oxidase (MAO). It can, however, be deaminated by MAO to produce phenylacetaldehyde, and subsequently phenylacetic acid. 5. Other hydrazine compounds, such as hydralazine, have also been found to be methylated by the adrenal enzyme. 6. Our finding of enzymatic methylation of hydrazine compounds is novel, and it may play a role in the metabolism of hydrazine drugs. PMID- 1871334 TI - [Function of transferrin and its receptor]. PMID- 1871335 TI - [Roles of protein kinase C substrates in signal transduction]. PMID- 1871336 TI - [Cell cycle and cell proliferation]. PMID- 1871337 TI - [Growth inhibitors and feedback regulation of cell proliferation]. PMID- 1871338 TI - [Regulation of cell growth by extracellular matrix system]. PMID- 1871339 TI - [Growth-stimulatory action of insulin]. PMID- 1871340 TI - [Interactions of the growth factors and the extracellular matrix components]. PMID- 1871341 TI - [Autocrine function of insulin-like growth factor-I]. PMID- 1871342 TI - [Cloning of proliferation-related early genes in hepatocytes]. PMID- 1871343 TI - [Production of growth factors by biotechnology and its applications]. PMID- 1871344 TI - [CSFs and regulatory mechanisms of their expression]. PMID- 1871345 TI - [Interleukin 2 and interleukin 2 receptors]. PMID- 1871346 TI - [IL-3: production mechanism and the receptor]. PMID- 1871347 TI - [The molecular mechanism of IL-4]. PMID- 1871348 TI - [Role of IL-5 and its receptor in immune system]. PMID- 1871349 TI - [Function of hemopoietic stem cells]. PMID- 1871350 TI - [Neural trophic factors and neuron-glia interaction]. PMID- 1871351 TI - [Renal growth factor; structure and roles]. PMID- 1871352 TI - [Production and tissue distribution of growth factors]. PMID- 1871353 TI - [Distribution of growth factor receptors in various human tissues]. PMID- 1871354 TI - [Cellular aging and growth factor]. PMID- 1871355 TI - [Physiological roles of growth factors in reproduction]. PMID- 1871356 TI - [Skin disease and growth factor]. PMID- 1871357 TI - [Structure and function of TGF-alpha]. PMID- 1871358 TI - [Functions of heparin binding growth factor (HBGF or FGF) produced by tumor cells]. PMID- 1871359 TI - [Involvement of proto-ret and activated ret in human malignancy]. PMID- 1871360 TI - [Implication of growth factors in tumor metastasis]. PMID- 1871361 TI - [Clinical application of growth factors--present states and future prospects]. PMID- 1871362 TI - [Abnormalities of the insulin receptor gene and diabetes mellitus]. PMID- 1871363 TI - [Pathophysiological analysis using cytokines working on lympho-hematopoietic cells]. PMID- 1871364 TI - [Inhibitors of growth factor functions, possible antineoplastic agents]. PMID- 1871366 TI - [Cultured skin prepared by using growth factor in the treatment of burn injury]. PMID- 1871365 TI - [Targeting therapy directed against growth factor receptor]. PMID- 1871367 TI - [Effect of epidermal growth factor on corneal wound healing]. PMID- 1871368 TI - [Clinical application of IL-1 beta]. PMID- 1871369 TI - [Clinical usefulness of various CSFs]. PMID- 1871370 TI - [Clinical application of erythropoietin]. PMID- 1871371 TI - [Growth factors: recent advances and perspectives]. PMID- 1871372 TI - [Altered responses of the variants with defective or low epidermal growth factor receptor activity]. PMID- 1871373 TI - [Gangliosides modulate function of EGF receptor]. PMID- 1871374 TI - [The regulatory mechanism of EGF receptor gene expression]. PMID- 1871375 TI - Prostaglandin D2 metabolite stimulates collagen synthesis by human osteoblasts during calcification. AB - We investigated the effect of the prostaglandin D2 metabolite delta 12-PGJ2 (9 Deoxy-delta 9, delta 12-13,14-dihydroprostaglandin 2D) on collagen synthesis in human osteoblasts. delta 12-PGJ2 at 10(-5) M enhanced collagen synthesis in the presence of 2 mM alpha-glycerophosphate-2Na. The stimulative effect appeared as early as 3 days after addition and continued until 22 days. The enhancement of type I collagen synthesis was confirmed by polyacrylamide gel electrophoresis. The potency was the same as 10(-8) M 1 alpha, 25 dihydroxy vitamin D3 (1,25(OH)2D3). Northern blot analysis showed that 10(-5) M delta 12-PGJ2 and 10( 8) M 1,25(OH)2D3 enhanced the transcription of type I procollagen (alpha 1) mRNA levels in osteoblasts. PMID- 1871376 TI - Prostaglandin E2 and leukotriene C4-induced luteinizing hormone-releasing hormone release from immature and adult male rat median eminences in vitro: eicosanoid formation and binding parameters. AB - The amounts of prostaglandin E2 formed in vitro by the median eminences of adult male rats were greater than those produced by the median eminences of immature, 22 day-old rats. However, the amount of leukotriene C4 produced by the adult rat median eminences was lower than that produced by the immature rat median eminences. Analysis of the prostaglandin E2 binding parameters of hypothalamic P2 membrane fractions indicates that there are two binding components, one high affinity (RH) and one low affinity (RL) in both adult and immature rats. The maximal binding capacity of RH from adult rat membranes was significantly lower than that of immature rat membranes, correlating with greater prostaglandin E2 production by the adult rat median eminence. Only one leukotriene C4 binding site was detected in both adult and immature rat membranes. Exogenous prostaglandin E2 and leukotriene C4 both stimulated, the release of luteinizing hormone-releasing hormone to the same extent from both the adult and immature median eminences. PMID- 1871377 TI - Mast cells in the rat gastric mucosa are not primarily responsible for PGD2 generation. AB - The present study investigates the contribution of gastric mast cells on PGD2 generation in rat gastric mucosa. Cold-restraint induced stress or i.v. carbachol injection methods were used for gastric mast cell degranulation. In 19 stressed, 15 carbachol-infused and 14 control rats, gastric mast cell counts and gastric mucosa PGD2 assay were performed. Gastric mucosal content of PGF2 alpha was also determined in carbachol infused and control rats. The mean number of gastric mast cells was significantly lower in stressed and carbachol infused than in control rats. Despite these differences in gastric mast cell counts, neither PGD2 or PGF2 alpha contents in the gastric mucosa were significantly different in mast cells degranulated rats than in control animals. These results suggest another source of PGD2 in the rat gastric mucosa other than mast cells. PMID- 1871378 TI - Effect of ICI 198,615, SK+F 104,353, MK-571 and CGP45715A on cysteinyl leukotriene-induced responses in guinea-pig heart. AB - Peptidoleukotrienes (LTs), LTC4 and LTD4, cause potent vasoconstriction and myocardial depression in a range of species including man. The recent availability of specific LTD4 antagonists has allowed the evaluation of LT involvement in disease states and the characterisation of LT receptors in the airways. We decided to study the actions of four LT antagonists; ICI 198,615, SK + F 104,353, MK-571 and CGP45715A on LTD4-, LTC4- and U46619-induced effects in the coronary vasculature and on cardiac contractility in the guinea-pig isolated heart. We found a difference in the actions of the antagonists in the GP heart compared with the lung. ICI 198,615 retained its selectivity towards LTD4 whereas SK + F 104,353 antagonised both LTD4 and LTC4. MK-571 and CGP45715A had a non specific action against the LTs. Our results also indicated a direct action of the LTs on cardiac contractility which was not associated with the constriction of the coronary vasculature. These studies indicate that if the leukotrienes are involved in cardiac disease antagonists specific for the peptidoleukotrienes may be of therapeutic benefit in many of the disease states of the heart. PMID- 1871379 TI - [Idea and reality of training analysis. A plea for reforms (II)]. AB - Thoma pleads for a form of psychoanalytic training in which the critical appropriation of psychoanalytic and humanistic knowledge as well as therapeutic competence are the focus and in which the personal analysis (super-therapy) is no longer overvalued. It seems possible to limit the length of training analyses. Qualification for professional practice should be worked out exclusively within the training institute and in close collaboration with instructors. PMID- 1871380 TI - ["Anxiety glistens on our brows". Dream reports in literary works on the horrors of ghettos and concentration camps]. AB - Dream reports occupy a special place in literature about confinement in concentration camps and ghettos (Robert Antelme, Charlotte Delbo, Anna Langfus, Andre Schwarz-Bart). They are central elements in the narrative that relate the anxiety of those threatened with destruction more faithfully than any realistic account could. They disrupt the chronological linearity and rationality and represent in images horror beyond memory or description. PMID- 1871381 TI - ["The story of my high school studies". An autobiographical fragment by Siegfried Bernfeld]. PMID- 1871382 TI - [Radiology and radioprotection in dental medicine. 2: Regulations and practical recommendations]. AB - The three general principles of the International Commission on Radiological Protection (ICRP) are first recalled: (1) justification, (2) ALARA, (3) the dose limits. The dose limits to be followed, at present, in Belgium are given for the occupational exposure, the occupational exposure of women (pregnant and not), the exposure of the public. The possible modification of the dose limits by the ICRP is a near future is discussed. The present belgian regulations are reviewed as far as the equipment and the buildings are concerned, as well as for the personal dosimeters and the medical supervision. Finally, the doses delivered to the patients, at different organs, during dental radiological examinations are recalled, e.g. the doses at the skin, the thyroid, the gonads, the eyes, the pituitary gland. The interest of shielding the thyroid and the abdomen is discussed. PMID- 1871383 TI - [Radiological information according to selected iconography]. AB - Every dentist can meet peculiar radiographic images that require a further investigation by a specialist in buccal pathology. This one can ensure the way to determine for example the tumoral or systemic character of the suspected lesion. Other morphological radiographic appearances include a risk of misinterpretation and thus inopportune, inadequate or hazardous operative procedures. This limited review with selected examples presents some occurrences the practitioner must keep in mind. Finally, this review demonstrates the need of correct radiographic knowledges and applications. PMID- 1871384 TI - [Medical imagery and its perspectives. Interview by Patrick Bogaerts]. PMID- 1871385 TI - [The value of current imagery techniques in dentistry and stomatology]. AB - Computed tomography, ultrasonography and magnetic resonance imaging are currently used in stomatology and dentistry. These recent imaging modalities have suppressed or reduced classic examinations (by example: conventional tomography and sialography). Efficient, exact and fast, they improve the diagnostic capacities and optimize the choice of the treatments. After some technical considerations, their applications in various stomatology and dentistry problems are evoked. PMID- 1871386 TI - [Radiology and radiation protection in dental medicine. 1: Biological effects resulting from exposure to ionizing radiation]. AB - The different types of biological effects produced by ionizing radiations are reviewed. Among the early effects following an acute exposure, the bone marrow syndrome and the intestinal syndrome are briefly described. They are unlikely to appear in the current conditions encountered in dental radiology. As far as skin exposure is concerned (e.g. fingers, hands), acute reactions (moist desquamation, ulceration, etc.) require high doses which are encountered only in accidental conditions. However, chronic dermatitis after repeated low dose exposure is one of the major risks in dental radiology (even without previous acute lesions), if the recommendations of radioprotection are not followed. The danger is ultimately the transformation into a radio-induced skin cancer. Among the late effects, after chronic exposure at low doses, cancer induction and the genetic effects are the most important. The risk coefficient for cancer induction is expressed by the number of lethal cancers induced per unit dose. In his last report (1988), the UNSCEAR assessed the risk coefficient between 4.5 and 7% for an absorbed dose of 1 Gy (low-LET radiation, high dose delivered at high dose rate). A low doses and low dose rates (X-and gamma rays), the UNSCEAR recommends to reduce the above risk coefficients by a factor between 2 and 10. The risk coefficient at low doses is difficult to evaluate since the rate of radio-induced cancers is small compared to the spontaneous cancer incidence. The risk of a severe genetic effect is about 1/3-1/4 of the risk of lethality from radio-induced cancer. Finally, the characteristics of the stochastic and non-stochastic effects are described. The acute effects, the late radiodermatitis and the cataract are examples of non stochastic effects, while cancer induction and the genetic effect are stochastic effects. In the Appendix, the most important quantities and units, used in radiation protection, are presented. PMID- 1871387 TI - [Clinical study of peri-abutment gingiva in patients with subperiosteal implants]. AB - A clinical analysis of the gingival tissues surrounding 17 subperiosteal dental implant posts was made. The clinical phase consisted in: Periodontal probe test locking for bleeding; peri-implant sulcus deep test; and the amount of bacterial plaque test on the subperiosteal post. The results showed clinically healthy tissues surrounding the subperiosteal posts. The presence of bacterial plaque is an important factor in the modification of the clinical inflammation parameters. PMID- 1871388 TI - [Anatomo-morphologic aspects of the jaws as indications for osseointegrated implants in the partially edentulous]. AB - Considering the great apogee reached in the last few years by the osseointegrated implants used in modern odontology it makes necessary to go deeper into the analysis of some anatomo-morphologic mandible aspects on partial edentates. Actually, these make the major percentage of patients who ask or are in effect candidates to rehabilitation by means of this technic. So it is described on individual analysis for each clinical case classified according to Kennedy's classification, giving emphasis to determination and real evaluation of height, thickness and form of partial edentates' mandibles. Furthermore, there are given some prosthetic models to be considered in the osseointegrated implant indications on partial edentates. PMID- 1871389 TI - [Alloplastic grafts in osseous reconstruction. Clinical experience with HTR]. AB - The present report reviews the clinical experience of the authors, with a new material in haloplastic grafts; the HTR; with the following purposes: Remain and or increase alveolar ridges. Close-up of congenital clefts. PMID- 1871390 TI - [Facial esthetics for the maxillo-facial surgeon]. AB - Has been pointed out that this is the aesthetic era for current dentistry. The oral and maxillo facial surgeon plays an important role in this regard emfatizing that the facial aesthetic is part of our field and responsibility in conjunction with the functional goal of most of our treatments. PMID- 1871391 TI - [Osseointegrated implants. Clinical cases and light and electron microscope study]. AB - Titanium osseointegrated implants have been placed in maxilaries of partially edentulous patients. After a follow-up of 5 to 6 months, a clinical and radiographical evaluation was made in order to determine the osseointegration obtained. In two of these cases, the gingival tissue in contact with the implants was studied under a light and transmission electron microscope. The results indicated a high percentage of implants were osseointegrated (99.72%), and the microscopical analysis showed a tissular reaction denoting biocompatibility with the implants. PMID- 1871392 TI - [Microscopic analysis of the effects of ultrasonic instrumentation on the root surface of molar furcations]. AB - Twenty molars, 10 from the maxilla and 10 from the mandible with furcation areas type II (Staffileno) were instrumented in their inter-radicular area with P10 instrument of Cavitron. It was established that the furcations of easier access instrumentation were the lingual o lower teeth and the buccal of the upper, and the most difficult accessibility were the distal of upper molars. The instrumentation can leave grooves or deformations, depending on the instrument to the area. It was concluded that ultrasonic instrument are useful removing supragingival calculus and bacterial plaque, and it must be limited to perform such procedures. PMID- 1871393 TI - [Overdentures as a solution for extensive loss of tooth structure. Clinical case]. AB - Extensive anterior teeth abrasions can be rehabilitated by the use of overdentures. Obtaining very good physiological and esthetical results. PMID- 1871394 TI - [Biological success in osseointegrated implants]. AB - Long term research results initiated by Dr. P. I. Branemark in 1965 and before, had widely demonstrated that with an adequate biomaterial, a phenomenon of biological acceptance from maxillary bone occurs, configurating a real bone healing, obtaining an intimate bonding between this alive tissue and the implant, which will last under function. Nevertheless, for this bio-physiological step happens and remain, there are many necessary factors named biological and biomechanical principles, and they command and are the responsibles of the osseointegration success. PMID- 1871395 TI - [Psychological and social evaluation]. AB - The purpose of psychological and social assessment of health programs is the measurement of psychological well-being and lifestyle in targeted populations (i.e. pregnant women, mothers, children or teenagers) and interactive effects on other family members. A psychological and social evaluation should contain the following elements: social and/or cultural factors that facilitate participation in a health program, the opinion of and satisfaction with the program, the psychological and social consequences of the program. Three types of tools can be utilized to measure psychological and social indicators: standardized questionnaires, questionnaires designed specifically for the study in question, and interviews. Study protocols, data collection and analyses must be done using the same methods as those used in any other type of medical evaluation. The investigator must be particularly sensitive to the quality of the measurement tools, the size of the sample and the effects of confounding factors. Social and psychological aspects are essential in the evaluation of a health program. On the one hand, they allow for an understanding of how a health program is accepted and applied within a population. On the other hand, they enable the verification of whether or not there has been any change in the quality of life among individuals and their families. PMID- 1871396 TI - [Evaluation of the application of laws or regulations]. AB - In the field of safety, accidents and injuries, laws and regulations can either ensure a passive protection of persons, or need their active participation. In the latter situation, beside the use of health indicators (rates of fatalities, accidents, injuries), the evaluation will also focus on changes of behaviour. In the case of mandatory restraint devices for young children, the evaluation of the laws indicates their effectiveness, but also: 1) methodological issues in interpretation of the results (reliability of the sources of information, choice of relevant denominators for the calculation of rates ...); 2) families low compliance, due to problems of acceptability of the laws and regulations, and to personal factors (demographic, socio-economic, cultural, and mainly psychological). PMID- 1871397 TI - [Epidemiological methods in evaluation]. AB - This paper describes different epidemiological methods to evaluate the effect of a public health intervention. The different types of indicators as well as types of evaluative surveys (experimental, quasi-experimental, observational) are presented. Criteria for choosing one type of survey are discussed. Examples of surveys are described. PMID- 1871398 TI - [Evaluation of screening programs]. AB - This paper discusses the specific aspects involved in the assessment of screening programmes, compared to the assessment of other types of public health interventions. Screening programmes are aimed at healthy asymptomatic individuals, who, in case of a positive test, will be exposed to subsequent investigations or treatments. This paper stresses upon the several aspects to be taken into consideration when assessing the potential benefits and hazards of a screening programme, especially in order to limit hazards linked to false positive results: predictive value of the test according to its diagnostic value and the disease prevalence, existence of effective "treatments" in case of positive test. It underlines the need for adequate methods to evaluate positive and negative health effects, and psychological and social consequences. PMID- 1871399 TI - [Epidemiological evaluation of 4 public health interventions]. AB - Methods for the epidemiological evaluation of interventions in Public Health are divided into experimental studies with randomization of "exposed" groups and "controls", and experimental studies without randomization where comparisons are made between periods of time ("before" and "after") or groups differing in their localization ("here" and "elsewhere"). Four attempts to evaluate interventions in Public health are presented. They were designed to appraise the efficiency of pregnancy survey by midwives acting at the home of pregnant women for the prevention of prematurity, to evaluate a program of prevention of ill-treatment of very young children, to assess a program of prevention of sexually transmitted diseases and of the impact of their complications on sterility, and to determine the effects of a campaign to support women having decided to breast-feed their babies. Despite the difficulties encountered in the definition of the protocols and their implementation these four surveys show that it is feasible to organize a network of professionals of various origins and to take into account professional constraints, ethical issues and the necessities of scientific evaluation. PMID- 1871400 TI - [Evaluation of health education programs]. AB - Health education may be defined as a process that seeks to achieve voluntary changes in behavior conducive to health. Systematic program planning, based on an extensive investigation of the needs of a specific population is essential if health education is to attain validity in the eyes of the public, health professionals and policy makers who assess its value. In addition, unless educational programs have clearly defined and measurable objectives, health education will continue to be an area that uses the measurement of activities, rather than the measurement of changes in behavior and health status, as its ultimate goal. The PRECEDE model, presented here, offers a quantifiable means of conducting an educational diagnosis in health, behavioral and cognitive, attitudinal and organizational terms before the development of an educational program. The process allows the practitioner to define objectives, which form the basis for subsequent analyses of the effectiveness of the program. PMID- 1871401 TI - [Percutaneous cardiopulmonary bypass. A procedure in the process of diffusion]. PMID- 1871402 TI - [Hypertrophic myocardiopathy (I). The clinical and echocardiographic characteristics of a population of 72 patients]. AB - The results of the echocardiographic evaluation of 72 patients with hypertrophic cardiomyopathy are presented. We have measured left ventricular wall thickness in 8 different segments and classified our patients in 6 types according to the hypertrophy extent. Moreover, we have evaluated by Doppler ultrasound the presence and severity of mitral regurgitation and the left ventricular inflow and outflow. The hypertrophy cardiomyopathy pattern was symmetric in 8 patients, apical in five, and asymmetric in 31. According to Maron classification, asymmetric cardiomyopathy was I type: 4 patients, II type: 16, III type: 11, and IV type: 0 patients. There were left ventricular outflow obstruction (greater than 25 mmHg) in 26 patients (36.1%). This obstruction was more frequent in II and III type hypertrophic cardiomyopathy and we found significative relationship between septal posterior segment hypertrophy and left ventricular outflow obstruction. Ventricular inflow showed bad distensibility pattern in 45 patients (62.5%). Mitral regurgitation was mild, moderate and severe in 25, 15, and 4 patients. Left ventricular outflow obstruction, bad distensibility pattern and mitral regurgitation were independent each other. PMID- 1871403 TI - [The atrial contribution to ventricular filling in mitral stenosis. An evaluation by Doppler echocardiography]. AB - Using Doppler echocardiography, we have quantified the atrial contribution to ventricular filling in 22 patients with mitral stenosis in sinus rhythm without or with minimal mitral and/or aortic regurgitation. With continuous wave Doppler from apex we obtained the ventricular filling flow from which the valvular area was calculated. The product of the integrated ventricular filling waves multiplying by the valvular area was called total volume (TV). Assuming that the deceleration of the ventricular filling flow is linear and remain constant, we integrated the transmitral flow, this time without considering the atrial filling wave as if the patient was entering into atrial fibrillation. Multiplying this integration by the valvular area we obtained a second volume, atrial fibrillation volume (AFV). The atrial contribution was calculated by: 1) absolute value: TV AFV and in 2) percent value or fraction: (TV-AFV/TV) x 100. When we correlate absolute and percent values with mitral valve area, the results were statistically significant in both cases (p less than 0.001), with an excellent regression factor both with absolute value r = 0.90 and the percent one r = 0.72. In mitral stenosis the atrial contribution to ventricular filling has an inverse relation with the grade of severity, being very low in the more severe lesions. This is why it would be doubtful that its lost (atrial contribution) is the only cause of hemodynamic deterioration that has been observed in patients who suddenly present atrial fibrillation. PMID- 1871404 TI - [Myocardial revascularization with the gastroepiploic artery. The initial experience]. AB - The internal mammary artery is widely recognized as the graft of choice for coronary artery bypass grafting at present. Alternative conduits have been investigated in order to find other adequate long-term grafts. The right gastroepiploic artery has been recently used as a graft to bypass distal coronary vessels. From November 1989 to April 1990 we have implanted this artery in 33 cases (32 in situ and one free grafts). The pedicled grafts were implanted in 17 patients in the main right coronary artery, in 13 we grafted the right distal branches, in one the left anterior descending, and the circumflex branch in one. The free graft was implanted in the first diagonal. Mean grafts per patient was of three in this series, with a mean of 2 arterial grafts per patient. One patient died in the early postoperative period. The remaining patients had an uncomplicated postoperative period. Thirteen patients underwent graft and coronary angiography. Direct or indirect graft patency was confirmed in all cases. The final important issue concerning the long-term patency of this graft will be solved in the future, but short-term patency rates of the right gastroepiploic artery can be anticipated when proper techniques are used. PMID- 1871405 TI - [The cardioprotective action of nifedipine during short-term transient ischemia]. AB - To determine the therapeutic activity on regional myocardial function of nifedipine intravenous administration (0.16 mg/kg) during short term myocardial induced ischemia, we used 6 mongrel dogs anesthetized and intubated those who we have implanted 3 pairs of ultrasonic crystals in the subendocardial layer. Utilizing an open chest canine model we performed total 1 minute and partial 2 minutes 30 seconds alternative obstructions, controlled with electromagnetic flowmeters in the anterior descending (AD) and circumflex (Cx) coronary arteries before and after drug administration. During the 70-80% obstructions we have shown a significant improvement in segment shortening, reduced by ischemia, in the ischemic and peri-ischemic zone. The ischemic markers, per cent increment of end diastolic length (% IEDL) and per cent increment of end systolic length (% IESL), have shown significant improvement during partial obstructions in the ischemic and peri-ischemic zone. After total obstructions the improvement on regional myocardial function is less marked and limited to ischemic zone. PMID- 1871406 TI - [Cardiovascular surgery in Spain in 1989. The Registry of Operations of the Spanish Society of Cardiovascular Surgery]. AB - The Spanish Society of Cardiovascular Surgery has sent a questionnaire to all 36 cardiovascular surgical groups to know the number and type of cardiovascular operations carried out in our country during 1989. The questionnaire was answered by 36 out of 36. In the year 1989, 20,912 cardiovascular patients have been operated upon and 9,582 interventions with extracorporeal circulation have been carried out: 45% in valvular disease, 34% in coronary and 13% in congenital. The number of operations was 5,771 for vascular disease, 4,272 for valvular, 3,296 for coronary, 1,973 for congenital and 3,031 for pacemaker implantation. Comparing with other countries, and specially with the Federal Republic of Germany, few points in our country deserve a remarkable mention: 1) Valvular pathology causes more operations than coronary one; 2) There is a low number of cardiovascular operations per million of inhabitants; 3) The cardiovascular surgical groups have a low yield. PMID- 1871407 TI - [Valvulopathies (XIV). The role of percutaneous valvuloplasty in congenital valvular diseases]. AB - The present article describes the cooperative experience Cordoba-Las Palmas since 1983 in 123 patients with congenital right or left ventricular outflow obstructions who were treated by percutaneous balloon dilatation. Seventy of them had pulmonary stenosis (63 valvular and seven supravalvular types); two had pulmonary atresia, 25 valvular aortic stenosis and 27 discrete subaortic stenosis. In patients with valvular pulmonic stenosis the gradient and the right ventricular pressure decreased significantly. No significant changes were observed in the degree of pulmonary regurgitation. One neonate died. No other major complications occurred. After a mean follow up of 3 +/- 2 years, we did not observe significant changes in the degree of pressure relief. The mean residual gradient is 26 +/- 19 mmHg. In our 21 patients out of the neonatal period with valvular aortic stenosis the gradient and the left ventricular pressure dropped significantly. Progression of aortic regurgitation in more than I grade was observed in 4 patients (19%), although only one (5%) progressed to grade III. There were no major complications in this group. After a mean follow up period of 24 +/- 17 months they persist with the obtained pressure relief and same degree of valvular competence. All 4 neonates with critical aortic stenosis had unsuccessful dilations and they died, wether after ulterior surgery or without it. In 27 patients with discrete subaortic stenosis the gradient and the left ventricular pressure decreased markedly, without significant changes in valve competence. There were no related major complications. After dilation, a broken and mobile membrane was frequently seen. At follow up (24 +/- 18 months), 6 patients (22%) had restenosis; five of them were successfully redilated. The remaining 21 patients persist with a reduced residual gradient (24 +/- 7 mmHg) and without significant changes in valve competence. PMID- 1871408 TI - [The double-orifice mitral valve. An evaluation by two-dimensional echocardiography and color echo-Doppler]. AB - Double-orifice mitral valve is an uncommon congenital heart defect. The isolated occurrence of this anomaly is exceptional and, more often, is encountered in association with other congenital cardiac abnormalities. Principal among these are the partial and complete forms of the atrioventricular canal. In this paper, we present two cases of double-orifice mitral valve. Our first case is associated with subaortic stenosis and coarctation of aorta. The second case is an isolated one resembling a severe mitral stenosis. As we know, the diagnosis of this rare anomaly by color-Doppler technique has not been previously reported. We believe this technique provides definite anatomical and functional information about double-orifice mitral valve. PMID- 1871409 TI - [Left ventricular perforation following percutaneous mitral valvuloplasty. Its emergency surgical correction in situ. Apropos a case]. AB - Percutaneous mitral valvuloplasty is actually accepted as alternative to surgery for treatment of rheumatic mitral stenosis, although today it is not still free from troublesome complications like ventricular perforation. We present here a patient in which was performed a percutaneous mitral valvuloplasty and that developed a left ventricular perforation at the end of the procedure, with hyperacute cardiac tamponade, requiring an in situ surgical salvagement on an emergency basis, performing a successful repair of the ventricular rupture in the own catheterization laboratory. PMID- 1871410 TI - [Two-dimensional color-Doppler in the diagnosis of left ventricle-right atrium shunts]. AB - Left ventricular to right atrial shunts, known as Gerbode's defects, are a kind of uncommon atrioventricular defect, the diagnostic of which had been always based on hemodynamic and angiographic findings. Although, at the present, this diagnosis can be done easily by color Doppler echocardiography, there are few references in the literature. We show 4 patients in whom the diagnosis was made by this technique, pointing out the aspects to keep in mind in order to avoid erroneous interpretations. The diagnostic criteria were: systolic turbulence and high velocity jet without pulmonary hypertension or right ventricular out flow stenosis. PMID- 1871411 TI - [A study of arteriosclerotic disease and of ischemic cardiopathy in particular and the associated risk factors in the Autonomous Basque Community. The Euzkadi project]. AB - The aim of the Euzkadi Project was to know the prevalence rate of cardiovascular disease and the high risk factors (hypertension, hypercholesterolemia and cigarette smoking) in the Basque Country to carry out an intervention trials to reduce these factors if we have collaboration of the Public Health Service. We have studied a sample of 4,800 men, 25-64 years old, randomly selected (1,600 men in each province), the examination was done by cardiologist using the cardiovascular questionnaire by Blackburn and Rose, the cholesterol was tested in WHO Collaborating Lipid Reference Center (Prague) and the electrocardiogram was studied by Minnesota Code. The rate of Atherosclerotic disease was 69%, coronary heart disease 49% (12% angina tipica, 9% angina atipica and 28% myocardial infarction), stroke 7%, and peripheral vascular disease 13%. The rate of silent myocardial infarction was 31%. The rate of hypertension was 24%, hypercholesterolemia 14% and cigarette smoking 40%. PMID- 1871412 TI - [Topographic diagnosis by two-dimensional echocardiography of an intramyocardial foreign body]. AB - A nineteen-year-old male was diagnosed as having a foreign body in his cardiac muscle after a mild open thoracic injury. Diagnosis and follow-up was performed by two-dimensional echocardiography. He did not show any complications after a 6 month follow-up. We emphasize the rare presentation of this entity and the usefulness of echocardiography to attain the foreign body's size and place. Also, echocardiography helps therapeutic management and diagnosis of complications. PMID- 1871413 TI - [Two-dimensional and color-coded Doppler echocardiography in the diagnosis of infradiaphragmatic total anomalous pulmonary venous connection (ITAPVC) to the portal venous system]. AB - We have studied by means of 2D echocardiogram and pulsed, continuous and codified colour Doppler, 3 newborns with a total anomalous infradiaphragmatic pulmonary venous connection to the portal vein. In the right subcostal projection we have observed the abnormal venous conduit crossing the diaphragm going to an enlarged portal system. The codified colour and the pulsed Doppler showed the venous characteristics and the abnormal direction of the flow. With these techniques it was also possible to detect the anatomic and functional intracardiac abnormalities. We consider these techniques a reliable method to make a surgical correction without the practise of any other invasive diagnostic method. PMID- 1871414 TI - Accumbens lesion in female rats increases mount rejection without modifying lordosis. AB - Ovariectomized Wistar rats received bilateral electrolytic (n = 24) or sham (n = 11) lesion of the nucleus accumbens. Following priming with estradiol benzoate (25 micrograms/rat) and progesterone (0.5 mg/rat) they were tested for sexual behavior with a stud male. Tests were carried out once prior to operation and twice postoperatively. Both lordosis and rejection behaviors as responses to male mount attempts were evaluated for each session. Proceptive patterns (hopping, darting and presenting) were also recorded. Females with accumbens lesion did not differ from control animals either with regard to lordosis or to soliciting behaviors. On the contrary, the lesioned group showed a statistically significant increase in rejection behavior in both postoperative sessions (p less than 0.05 and p less than 0.002). In conclusion, nucleus accumbens lesion dissociated the normal correlation between lordosis and rejection responses to male mount attempts without affecting soliciting behaviors. This finding is thought to be related to the hyperreactivity produced by nucleus accumbens lesion. PMID- 1871415 TI - [Variations induced by juvenile hormone and precocene II in the metabolic rate of 3 species of insects]. AB - The effects of juvenile hormone and precocoene II on the metabolic rate of Blattela germanica L. (Blattaria, Blattellidae), Spilostethus pandurus Scop. (Heteroptera: Lygaeidae) and Oncopeltus fasciatus Dallas (Heteroptera: Lygaeidae) 5th instar nymphs and adults have been investigated. Direct volumetric method was used to determine the oxygen consumption rate. JH produced a stage and/or sex dependent increase in the metabolic rate according to the species considered. On the other hand, PII decreased oxygen consumption in Blattella germanica and S. pandurus fifth instar and males, whereas O. fasciatus metabolic rate was not affected by the treatment. PMID- 1871416 TI - Angiotensin II increases MAO activity in rat central nervous system. AB - The effects of angiotensin II (ANG II) and bilateral nephrectomy on monoamine oxidase (MAO) activity were studied in rat hypothalamus and medulla oblongata. ANG II increased MAO activity in both central nervous system (CNS) regions. The fall of circulating ANG II caused by 48 h bilateral nephrectomy decreased the activity of the enzyme in the mentioned areas. The results showed that ANG II stimulates catecholamine metabolism in the CNS. PMID- 1871417 TI - Cafeteria diet induced obesity in rats is dependent on parity of dams. PMID- 1871418 TI - Total serum IgE concentration in splenectomized patients after abdominal trauma. PMID- 1871419 TI - [The significance of intra-clinical outcome criteria in geriatric rehabilitation- results of an after-care project on the issue of quality assurance]. AB - Given the need for long-term quality assurance in the rehabilitation of geriatric patients, it is appropriate to inquire into the relevancy of intra-clinical outcome criteria for the patients' everyday life. It is assumed that everyday life at home will differ substantially from clinic routines, and that the rehabilitation potential achieved in the clinic will not as a matter of course be transferable. The findings of a follow-up project clearly show that long-term maintenance of rehabilitation potential, i.e. quality assurance, may be endangered primarily in three dimensions--psychic, social, and organizational. An orientation by purely intra-clinical outcome criteria of short reach (self-care, ADL, etc.), therefore, is contrasted with the consideration of psychosocial outcome criteria of long reach (quality of life, competence) in assessing rehabilitation outcome. PMID- 1871420 TI - [Interdisciplinary cooperation in rehabilitation--problem solving following severe craniocerebral injury]. AB - Therapy and rehabilitation of patients with craniocerebral trauma is particularly difficult to programme on account of the neuropsychological defects and personality changes found in this population. The Ulm rehabilitation hospital seeks to face up to this fact by intense interdisciplinary cooperation in the nursing and medical sector, the fields of logopaedics, Occupational Therapy, physiotherapy, immediate post-acute therapy including cerebral training, as well as the entire field of vocational rehabilitation. A dense time schedule has been established for graded introduction of the necessary therapeutic interventions in the sense of a therapy chain, with intense information flows among the therapists involved, thus ensuring a continuous process and joint adjustment of programming to the individual course, to new problems that may arise. The implementation of this concept is set out on the example of a young patient with craniocerebral injury, who had received treatment in various of our departments for a total of 12 months, finally bringing him up to the conclusion of his vocational education. PMID- 1871421 TI - [Fitness assessment and work therapy in a Phase II facility--a case example]. AB - A case example is used to set out the practice of vocational assessment and work adjustment in a medical-vocational, i.e. Phase II, facility. Formulated jointly by the rehabilitation team, the basic therapy objectives, by constant liaison with the employer, are differentiated in view of the future place of work and the performance required from the patient. The individual case serves to illustrate the effectiveness of this therapy approach intended to smoothen the transition from inpatient treatment to vocational reintegration. PMID- 1871422 TI - [Efficacy of combined relaxation exercises for children with bronchial asthma]. AB - In the framework of a pilot study, 15 children having bronchial asthma (4 female, 11 male; age 5-11;6) participated, over a period of 8 weeks, in two weekly sessions of combined relaxation, respiratory and sports exercises. The present article in particular focuses on the relaxation exercises, made up of Progressive Muscle Relaxation and Autogenic Training elements as well as of phantasy travels, mantras, and periodic music. Ongoing observation of the children during training, the findings of subsequent semi-structured interviews with them, topical instances of coping with impending asthma attacks by using the techniques learned, as well as the results of a catamnestic inquiry some three years later- all indicate a positive impact of the relaxation exercises. Statistical analysis of the data at hand revealed significant improvements in a number of pulmonary function parameters (airway resistance, forced expiratory volume for 1 s, forced vital capacity, peak expiratory flow rate). Interpretation of these findings must however take into account the entirety of the training provided. PMID- 1871423 TI - Escherichia coli DNA-binding protein H-NS is localized in the nucleoid. AB - Electron microscope localization of the 15.4-kDa DNA-binding protein H-NS was carried out in Escherichia coli cells subjected to cryosubstitution followed by immuno-labelling with the protein A/gold technique. Three types of E. coli cells were used: (1) "normal" cells growing exponentially at 37 degrees C; (2) "cold shocked" cells two hours after the shift from 37 degrees C to 10 degrees C; and (3) cells in which an expression vector had been induced to overproduce H-NS. The results clearly indicate that in all 3 cases, the vast majority of the molecules reacting with anti-H-NS antibodies are localized within the nucleoid and at the border between the nucleoid and the ribosome-rich cytoplasm, which supports the premise that H-NS is implicated in the condensation of the nucleoid. PMID- 1871424 TI - Structure and stereochemistry of mycolic acids of Mycobacterium marinum and Mycobacterium ulcerans. AB - Mycobacterium marinum and M. ulcerans were previously shown to synthesize lipid compounds which are stereochemically different from the corresponding molecules isolated from M. tuberculosis and other species. Stereochemical and biogenetic studies of mycolic acids isolated from M. marinum showed that the absolute configurations of the chiral centres occurring in the mycolates are identical to those of the other mycobacterial species examined so far. Furthermore, all the methyl branches were found to come from methionine whatever the configuration of the centre. The structures of the mycolates synthesized by M. marinum and M. ulcerans were found to be identical, consisting of dicyclopropyl and monocyclopropyl monoenoic mycolates, monoenoic keto- and methoxymycolates, thus reinforcing the taxonomical relationship between the two species. PMID- 1871425 TI - Further stereochemical studies of phthiocerol and phenol phthiocerol in mycobacteria. AB - Mycobacterium tuberculosis, M. marinum and some other pathogenic species elaborate waxes A, based on a long-chain beta-diol (phthiocerol and companion compounds) and polymethyl-branched fatty acids. The stereochemical studies conducted on waxes A showed that those of M. tuberculosis, M. leprae and M. kansasii differ from waxes A isolated from M. marinum and M. ulcerans by the absolute configuration of the methyl-branched chiral centres occurring in both the long-chain beta-diols and the fatty acyls. Furthermore, the two mycobacterial groups also differ in the stereochemistry of the beta-diol chiral centres. PMID- 1871426 TI - Multiplication and persistence of Spiroplasma melliferum strain A56 in experimentally infected suckling mice. AB - Strain A56 of the bee pathogen Spiroplasma melliferum was isolated from a honeybee (Apis mellifera) during ecological studies on mosquito spiroplasmas in Savoie (France). When inoculated intracerebrally (i.c.) into 48-h old suckling mice, this strain was found to replicate to very high titres and to persist in brain for up to 9 months in one individual. We attempted to increase the "neurotropism" of A56 by sequential i.c. passages. During the first two passages, multiplication of the organisms was observed at very high titres in suckling mouse brain (10(7) to 10(11) CCU/ml) generally without the appearance of antibody, thus mimicking the so-called "immunological tolerance" phenomenon. Intracerebral multiplication of A56 decreased during the third passage (10(2) to 10(4) CCU/ml) and ceased during the fourth passage. Spiroplasma multiplication in brain was apparently well tolerated, since brain lesions were minimal and clinical symptoms were limited to a clear, but only rarely significant, delay in growth curves of inoculated versus non-inoculated mice. Progressive spongiform encephalopathy was never observed. Strain A56 S. melliferum appears as the second spiroplasma, after the tick-derived Spiroplasma mirum capable of multiplying in both invertebrate and vertebrate hosts. PMID- 1871427 TI - Chemical principles in the organization of lipid components in the mycobacterial cell envelope. PMID- 1871428 TI - Contributing factors of pathogenesis in the Mycobacterium avium complex. PMID- 1871429 TI - Mycobacterial cell wall and pathogenicity: a lipodologist's view. PMID- 1871430 TI - Permeability of the mycobacterial cell wall. PMID- 1871431 TI - Structure-to-function relationship of mycobacterial cell envelope components. PMID- 1871432 TI - Studies on the role of the mycobacterial cell envelope in the multiple drug resistance of atypical mycobacteria. PMID- 1871433 TI - Structure, function and biogenesis of the cell envelope of mycobacteria in relation to bacterial physiology, pathogenesis and drug resistance; some thoughts and possibilities arising from recent structural information. PMID- 1871434 TI - Recent observations concerning structure and function relationships in the mycobacterial cell envelope: elaboration of a model in terms of mycobacterial pathogenicity, virulence and drug-resistance. PMID- 1871435 TI - [Eosinophil-induced lung injury]. PMID- 1871436 TI - [Prognosis of chronic heart failure]. PMID- 1871437 TI - [Arterial oxygen saturation monitoring with pulse oximeter]. PMID- 1871438 TI - [Teflon mandril method for pre-clotting a highly porous small-caliber fabric prosthesis]. AB - Healing characteristics in a highly porous fabric prosthesis are better than in a porous low one. However, bleeding from the highly porous graft wall after implantation has been a very big problem for surgeons, preventing them from using this prosthesis. When a small-caliber graft is pre-clotted and implanted, the condition of the inner surface, such as smoothness, enhances patency and anti thrombogenicity. We developed a method for pre-clotting a highly porous small caliber fabric prosthesis using Teflon Mandril. Before pre-clotting, a fabric vascular prosthesis was held end-to-end and stretched to make the crimp shallow. Teflon stick, which outer diameter was 0.5 mm smaller than the graft, was used to pre-clot. Fresh blood was poured into the space between the stick and the vascular graft. After 3 to 5 minutes, when the blood coagulated, the vascular graft with the stick inside was squeezed with a dry towel. Care was taken not to peel the fibrin attached to the graft. With this method, a smooth and tight fibrin meshwork was obtained at the inner surface. This procedure was repeated five times. As a control, pre-clotting was induced according to Yate's method using the same fabric prosthesis. Two groups of pre-clotted grafts were examined macroscopically and in a perfusion model. Macroscopically, the inside of the graft in the developed method was smooth and without thrombus. On the other hand, in the control grafts, the fibrin meshwork was observed and thrombus at the crimp was noticed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871439 TI - [Pathology of pulmonary embolism]. AB - The incidence of pulmonary embolism was surveyed in 500 serial autopsy records (1984-1989) in Nagoya University Hospital. This disease occurred in 77 cases (15.4%) and acute fatal pulmonary embolism was the cause of death in 30 cases (6.0%). This incidence was higher than has previously been reported in Japan, and almost the same as the incidence reported is USA or Western Europe. Thromboembolism was the major cause of this phenomenon in our series. Thirty-four cases were thrombo-embolized. Venous thrombi in 15 cases resulted from intravenous catheter. Tumor emboli were observed in 18 cases, bone or soft part sarcomas in 6 cases, hepatocellular carcinomas in 6 and renal cell carcinomas in 3. Fungus emboli were observed in 19 cases. Aspergillus was the major cause of thrombi in 14 immunocompromised patients. Six typical cases (1. post traumatic thromboembolism, 2. fatal thromboembolism due to catheter, 3. tumor embolism, 4. fungal embolism, 5. amniotic fluid embolism and 6. bone marrow embolism) were discussed from the viewpoint of clinicopathology. PMID- 1871440 TI - [Optimal pressure support ventilation as studied in a mathematical model]. AB - To determine the optimal pressure support (PS) level in pressure support ventilations (PSV), we combined a mathematical model representing lung mechanics and alveolar gas exchange with a PS respirator model. As suggested by Fiastro et al. (1988), we defined the optimal PS level with regard to the work of breathing in such a way that the external inspiratory work of breathing equalled zero. We found that the optimal PS level determined as above resulted in the mean airway pressure calculated during an inspiratory phase being equal to zero (or a CPAP level). Thus we suggest that the optimal pressure support in terms of the work of breathing could be accomplished without a direct calculation of the work of breathing. PMID- 1871441 TI - [Influence of reperfusion therapy on left ventricular remodeling after acute myocardial infarction]. AB - To determine the relation between reperfusion therapy and left ventricular function and remodeling after acute myocardial infarction (AMI), 75 consecutive patients with anterior AMI were studied. The patients were divided into four groups according to the reperfusion outcome and time to reperfusion from onset of MI: 12 patients with spontaneous reperfusion, 18 patients with early (less than 4th) successful reperfusion, 16 patients with late (greater than or equal to 4th) successful reperfusion and 29 patients with unsuccessful reperfusion. The right oblique left ventriculograms (LVG), which was performed early (n = 19) and late after infarction (n = 75) were analyzed to assess left ventricular (LV) volume and global and regional LV function. At the late examination, spontaneous early and late reperfused patients showed smaller LV volume (endo diastolic and endo systolic volume index) than unsuccessfully reperfused patients LV volume was similar in both early and late reperfused patients. Spontaneous and early reperfused patients showed higher LV ejection fraction (EF) and better regional wall motion (RWM) than unsuccessfully reperfused patients. Both EF and RWM was similar in late and unsuccessfully reperfused patients at the late examination. Endo-diastolic and endo-systolic volume index increased significantly with time in patients with unsuccessful reperfusion (n = 10), as compared with the index found in the early examination. In patients with late reperfusion (n = 5), end diastolic volume index increased with time, but end-systolic volume index was unchanged. RMW improved in patients with early reperfusion (n = 4), but was unchanged in patients with late and unsuccessful reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871442 TI - [Effects of isosorbide dinitrate on coronary and systemic circulation in children]. AB - The effects of isosorbide dinitrate (ISDN) on the coronary and systemic circulation were evaluated in 8 children with angiographically normal coronary arteries. ISDN, 100 micrograms/kg, was given as a intracoronary injection. The pulmonary artery pressure, pulmonary capillary wedge pressure and left ventricular end diastolic pressure which are related to the pre-load were significantly reduced 1 min after the ISDN injection. The systolic blood pressure was reduced, and heart rate increased. The cardiac output, pressure-rate product and systemic vascular resistance showed no significant change. The systolic work index, however, was significantly reduced. ISDN induced a significant dilatation, ranging from 4.0% to 12.9%, in the diameter of the coronary vessels. There was, however, no change in the coronary blood flow, coronary perfusion pressure and coronary vascular resistance. The grade of the dilatation of the coronary vessels by ISDN in children was lower as compared with that in adult. PMID- 1871443 TI - [A case of multiple myeloma with heart failure improved remarkably by chemotherapy alone]. AB - A rare case is reported, in which heart failure in a patient with multiple myeloma without amyloidosis was improved following chemotherapy for the myeloma. The patient, a 50 year-old man, came to our hospital for examination because of anemia and hematuria. He was diagnosed as having an IgG kappa type of myeloma with the relatively rare complication of renal cancer. A chest X-ray revealed cardiomegaly and pulmonary congestion. An echocardiogram revealed an enlarged left ventricle with decreased wall motion. No cardiac amyloid deposits were detected upon endomyocardial biopsy. Chemotherapy for the myeloma which was carried out before the operation for renal cancer was not only effective for control of the myeloma, but also decreased the pulmonary congestion and improved the heart function. It is suggested that the lowering of heart function in this patient was not due to amyloid infiltration as is relatively frequent in heart failure but was due to increased blood viscosity due to the multiple myeloma. PMID- 1871444 TI - [A case of fulminant hepatic failure secondary to congestive heart failure]. AB - It has been generally accepted that congestive heart failure does not lead to fulminant hepatic failure, unless it is associated with cardiac shock or low cardiac output. Only three cases have been reported, in which liver congestion is followed by fulminant hepatic failure without a history of shock or low cardiac output. Here we present a case of a 48-year-old man with dilated cardiomyopathy and pulmonary infarction, who developed fulminant hepatic failure from congestion. When he was admitted for the control of diabetes mellitus, hepatomegaly of 3-finger breadth and marked cardiomegaly without pulmonary congestion was noted. Diabetes was controlled using insulin. But 3 weeks after admission, he sometimes complained of back dullness because of pulmonary infarction. His heart gradually increased in size, and Jugular venous dilatation and pretibial pitting edema also worsened. Jaundice was noted and serum GOT and GPT increased. A large liver of 6-finger breath below the right costal margin was able to be felt. But within one week, the size of the liver markedly decreased and the signs of hepatic failure such as jaundice, hepatic encephalopathy and numerous petechiae appeared. Blood pressure was maintained and no hypotension or cardiac shock was noted. The patient died of fulminant hepatic failure on the 20th days after onset of the hepatic failure. The autopsy revealed liver atrophy with severe central lobular necrosis, and thrombus in the right main pulmonary artery which caused severe pulmonary infarction. The mechanism of fulminant hepatic failure not accompanied with low cardiac output is discussed. PMID- 1871445 TI - [Hypertrophic cardiomyopathy associated with anomalous origin of the left coronary artery from the right sinus of valsalva]. AB - A 47 year old Japanese male with exertional shortness of breath, cardiac murmur and ECG abnormalities was examined with invasive and non-invasive cardiology techniques that disclosed hypertrophic cardiomyopathy, and the anomalous origin of the left coronary artery from the right sinus of Valsalva. Although both situations have been known to cause sudden death especially under a state of strenuous physical stress, his exercise thallium scintigraphy performed with the symptom limited maximal test did not uncover any significant myocardial ischemia or exercise induced malignant arrhythmias. This is a very rare association of two distinctly identified clinical situations highly indicative of a likelihood of sudden cardiac death. Therefore, careful observation is needed. PMID- 1871446 TI - [Acute congestive heart failure due to malignant rheumatoid arthritis]. AB - A 54-year-old woman with malignant rheumatoid arthritis was admitted with acute congestive heart failure and pulmonary hypertension. The precipitating antibody to nuclear ribonucleoprotein (nRNP) was highly positive. Her hands and feet showed typical rheumatoid deformities and Raynaud's phenomenon. In a few days her feet became to necrosis due to vasculitis. "Pulse" methylprednisolone and prednisone therapy resulted in normalization of seropositivity, and left ventricular ejection fraction with symptoms of congestive heart failure, and the elimination of ECG abnormalities. Recognition of symptoms of left ventricular dysfunction in patients with rheumatoid arthritis should prompt testing for active arteritis and/or myocarditis, because dramatic improvement may result from immunosuppressive therapy. PMID- 1871447 TI - Cutaneous pseudo-T-cell lymphomas. PMID- 1871448 TI - Actinic reticuloid. AB - AR can be regarded as the most severe variant of the spectrum of chronic actinic dermatitis. The exact etiology is still unknown, but is probably multifactorial, involving contact allergic, photoallergenic, phototoxic, immunologic, and metabolic factors. A diagnosis of AR should only be made when the following criteria are present: (1) persistent infiltrated papules and plaques on light exposed skin, often with extension to covered areas or generalized infiltrated erythroderma; (2) photosensitivity to a broad spectrum of wavelengths, including UV-B, UV-A, and part of the visible spectrum; and (3) on histologic examination, a dermal infiltrate with presence of atypical lymphoid cells. When one or two criteria are lacking, the more general term chronic actinic dermatitis should be preferred. The presence of a lymphoid infiltrate dominated by CD8+ cells seems to be useful as an additional marker for a diagnosis of AR. A CD8+ predominance in dermal infiltrates is exceptional and has been reported in clinically distinguished conditions such as graft-versus-host disease, lichen planus, erythema multiforme, and pityriasis lichenoides acuta, as well as chronica, and, finally, in mycosis fungoides. In erythrodermic patients, the presence of a CD8+ dominated dermal infiltrate and, especially, a reversed CD4+ to CD8+ ratio in the peripheral blood are highly characteristic for a definite diagnosis of AR. It is not known why preferentially CD8+ lymphocytes occur in AR. Exposure to UV radiation can induce the presence of suppressor cells. In late lesions of polymorphic light eruption, there is also an increase of CD8+ cells as compared with early lesions, perhaps contributing to local suppression of the inflammatory response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871449 TI - Seminars in diagnostic pathology. Introduction. PMID- 1871450 TI - The morphologic spectrum of T-cell lymphomas of the skin: a proposal for a new classification. PMID- 1871451 TI - Immunohistological markers for the diagnosis of cutaneous lymphomas. PMID- 1871452 TI - Variants of mycosis fungoides and related cutaneous T-cell lymphomas. PMID- 1871453 TI - Reticulohistiocytoma of the dorsum (Crosti's disease) and other B-cell lymphomas. PMID- 1871454 TI - Intravascular lymphomatosis: clinicopathologic features and differential diagnosis. PMID- 1871455 TI - [Pathologic processes of lumbar primary sensory neurons produced by high doses of pyridoxine in rats--morphometric and electron microscopic studies]. AB - The morphologic effects of the toxicity of high doses of pyridoxine hydrochloride (vitamin B6) on the lumbar primary sensory neurons in rats were studied. The test rats were treated with 1,200 mg/kg of pyridoxine hydrochloride by intraperitoneal injection once a day, and were sacrificed by perfusion at periods ranging from one to seven days after the injection, together with the control rats. Initial lesions consisted of eccentricity and crenation of the nucleus and vacuole formation in the cytoplasm of large dorsal root ganglion neurons, 2 days after the injection. These lesions were followed by segregation of the nucleolus, axon reaction-like changes in the cytoplasm and axonal degeneration of both peripheral axons in the sural nerve and central axons in the fasciculus gracilis. The frequency of teased myelinated fibers showing axonal degeneration during tests was significantly greater than in control 3 to 7 days after the injection. No significant difference of such frequency was found between the proximal and distal sural nerve during tests. The number of large myelinated fibers per nerve in the sural nerve, when compared with control, was preferentially decreased during tests. In the fasciculus gracilis, the decrease of the density of myelinated fibers was more pronounced in the third cervical segment than in the fifth thoracic segment. Because both peripheral and central axons were similarly affected and the initial lesions were found in the neuronal cell body, the mode of degeneration of axons in this study was regarded as "neuronopathy". By both light and electron microscopy, accumulation of mitochondria, vesicles, multilamellar and dense bodies were found in the nodal and distal paranodal axons of myelinated fibers in the sixth dorsal root ganglion on the 2nd day after the injection, which preceded the degeneration of both peripheral and central axons. Such accumulation, revealed for the first time in this study, may reflect the presence of a blockade of the axoplasmic transport in the proximal axon and cell body of the lumbar primary sensory neuron and subsequently give rise to the degeneration of both peripheral and central axons of the lumbar primary sensory neuron. The pathologic alterations at the different sites of the lumbar primary sensory neuron revealed in this study should be taken into consideration for the better understanding not only of the pathogenesis of human pyridoxine-induced sensory neuropathy, but also of other human and experimental neuropathies. PMID- 1871456 TI - Clinicopathological study of pulmonary giant cell carcinomas with reference to prognosis of patients. AB - Giant cell carcinomas of the lung have been notorious in fulminant clinical courses. Thus, this report describes two exceptionally favorable cases among six cases of giant cell carcinoma of the lung. Their histopathological features are a sharply-demarcated tumor of Stage I, absence of vascular permeation of the cancer cells, prominent lymphoid and plasma cell infiltration in the tumor tissue, and lymph follicle formation in the surrounding tissues. Another case with a Stage II tumor showed the same histopathological findings as the above two cases with the exception of lymphatic permeation of the cancer cells. This patient expired about one year after undergoing an operation. As conventional controls, the remaining three cases with Stage III tumors showed an alveolar extension of tumor cells and vascular permeation. There was a fulminant course after the operation. Notwithstanding similar intervals from their clinical onset to operation in the 4 cases other than Cases 4 and 6, their stages showed considerable variations. Hence, each histopathological feature might have substantiated the different clinical courses following the operation. Electron microscopy of three of the cases indicated double-membrane-bound blisters with intermediate junctions in the bizarre giant cells, and cancer cell differentiation toward both glandular and squamous directions. PMID- 1871457 TI - Effects of hyperbaric environment on the P300 component of event-related potentials. AB - Hyperbaric chamber dives at 19 ATA with helium-oxygen were performed at the Japan Marine Science Technology Center, Yokosuka, from January 31 to February 2 in 1990. During simulated underwater experiments, event-related potentials were recorded in 2 divers for assessment of the cognitive function. Although the P300 amplitude of the potentials did not show any significant change, its latency was clearly prolongated and this prolongation continued to when the decompression reached to 70 m below sea level. These findings indicated that the hyperbaric environment corresponding to 180 m below sea level or less must cause some cognitive dysfunctions and that P300 is useful for early detection of those dysfunctions or HPNS. PMID- 1871458 TI - [Medical students' images of the occupational health physician--on the evaluation of motivation in medical education]. AB - One of the aims of the University of Occupational and Environmental Health, Japan, is to educate students to become occupational health physicians. However, the number of students who enter the university without an understanding of this aim is large. Therefore, the course titled 'Introductory Lectures on Occupational and Environmental Health' was planned for the 2nd-year students with the purpose of giving them the motivation to become occupational health physicians. Surveys of students' images of the term "occupational health physician" before and after taking the course were accomplished using the method of 'Monju card', that is, three students, in turn, write their ideas of an occupational health physician on a card. Moreover, after the series of lectures, students were assigned a self evaluation regarding the improvement of their images. The results of these surveys show that favorable images increased after the course, that classes offering information regarding the occupational health physician had an influence on the improvement of the images, and that students desire more such information. However, as some students indicated a strong rejection to becoming occupational health physicians throughout the course, a different type of course, and a new philosophy regarding the training of medical students may be necessary. PMID- 1871459 TI - [Problems in brain death--comparison of Germany and Japan]. PMID- 1871460 TI - [Post-concussion syndrome: organic lesions and/or functional brain disorders? How to assess this in a medicolegal context?]. PMID- 1871462 TI - [The HELLP syndrome. Main aspects and review of cases]. PMID- 1871461 TI - [Cardiac transplantation. Current aspects exemplified by personal experience]. PMID- 1871463 TI - [Compliance: a health problem]. PMID- 1871464 TI - [Current therapeutic agents 1989-1990]. PMID- 1871465 TI - [Recurrent benign intrahepatic cholestasis]. PMID- 1871466 TI - [Valve replacement for endocarditis due to Cardiobacterium hominis]. PMID- 1871467 TI - [Mycotic pseudo-aneurysm]. PMID- 1871468 TI - [Anatomo-clinical conference. Multiple pulmonary masses and Wegener's disease: diagnosis and treatment with anti-infective agents]. PMID- 1871469 TI - [What is your diagnosis? B). Diphyllobothriasis. C). Feces examination for helminths]. PMID- 1871470 TI - [Therapy of hypercholesterolemia--when, who, how?]. PMID- 1871471 TI - [The oncologist and his patient]. AB - The motifs of medical practise, in particular by the oncologist and the basic experience of the patient notably the cancer patient are presented. They represent the prerequisite for an individually taylored, solid relationship between physician and patient founding on mutual trust. Medical practise is nowadays founded on a scientific rationale. In contrast to earlier times the ethos of compassion pertains the private sphere. It is the physicians individual choice to proffer the traditional compassion as interest in the fate of an individual patient or not. The fundamental experience of an individual that his destiny lies no longer in his own hands expresses itself in a paradigmatic way by the perception of his illness. The cancer patient experiences--as other patients do--the threats but also his healing as occurrences not caused by him. He therefore does not identify his disease with objective impairments or pathologic findings. On the contrary, he perceives it as a threat to himself, his existence and his personality. The patient experiences his fate, to depend on circumstances and particularly on other individuals, their benevolence, their acceptance, their help. Trust is the basis for relationship between the cancer patient and his physician. Trust is also acceptance of dependence. Dependence is only acceptable if the physician is trustworthy. Trustworthiness cannot be gained by scientific competence alone but requires personal affection by compassion with the patients fate. The physician needs ethical competence to fulfill his task. Information of the patient gains a particular importance in this context. It, as well as the divergent assessment of the disease by patient and physician--the anthropologic difference--and the "equilibrating systems" are exposed. PMID- 1871472 TI - [Performing self-measurement of blood pressure: a patient survey]. AB - In the present study the knowledge of 200 patients of our hypertension clinic about the technique of blood-pressure self-measurement was investigated using a questionnaire of 22 questions. 44-66% of the patients in different age groups measured their own blood-pressure, showing that self-measurement is commonly used, regardless of the age. 73% of the patients had bought a device on their own, but only 17% on the physician's advice. Possible causes for erroneous measurements were rarely known and underestimated by the patients. Due to lacking or insufficient instruction a relatively high percentage of the patients did not perform correct measurements. 45% did not measure the blood-pressure at the same time of day, 45% did not read systolic and diastolic pressures to the nearest 2 mmHg mark of the manometer scale, 59% did not count the pulse rate and 52% did not document the blood-pressure values. About half of the patients adjusted their medication on the ground of self-measured blood-pressure determinations. 45% of the elderly patients felt that their compliance had improved by self-measurement in contrast to 17% in the younger group. Given the increasing use of blood pressure self-measurement we conclude that education of patients and physicians on possibilities and limitations of self-measurement as well as optimal training in the correct technique seem advisable. PMID- 1871473 TI - [Dimethindene maleate administered via intramuscular route in man: local and systemic tolerance]. AB - Local and systemic tolerance of dimethindene maleate was studied in 10 healthy volunteers by the intramuscular route (4 mg in 4 ml solvent). Subjective perception of pain and other reported side effects were registered and objective signs at the injection site were assessed repeatedly. Hematologic and biochemical tests were performed before and after completion of the study. Two volunteers complained about local pain immediately and one hour after the injection. An other volunteer developed a small hematoma within 48 hours after injection. No other side effects or adverse reactions were noted. Good tolerance of dimethindene maleate after intramuscular application could thus be established. PMID- 1871474 TI - [Routine screening for Chlamydia: is it sensible during pregnancy?]. AB - 610 pregnant patients were examined for evidence of Chlamydia trachomatis infection. Chlamydia trachomatis could be detected in 18 of these 610 patients. This results in a low prevalence rate of 3%; therefore, screening for Chlamydia trachomatis is not indicated in our pregnant population. Among the 18 chlamydia positive patients we could not discover any risk factors that were associated with this infection. Because of the varied and sometimes silent course in affected patients, this special investigation should be used liberally in a variety of situations. PMID- 1871475 TI - [Fever, swelling of testis and epididymis, poly-lymphadenopathy, splenomegaly]. AB - An 18-year-old Turkish farmer was admitted to the hospital because of fever, painful scrotal swelling, generalized lymph-node enlargement and splenomegaly. After an incubation period of six days Brucella melitensis was isolated in blood culture. The diagnosis of acute brucellosis with lymphadenopathy, splenomegaly and epididymitis was made. He was treated with doxycycline and Rifampicin for six weeks and recovered completely. Three months after therapy he felt well. A relapse did not occur. PMID- 1871476 TI - [A case from practice (215). Crohn's disease with involvement of the terminal ileum, cecum, ascending colon and development of a peri-anal fistula with accompanying entero-arthritis (Bilateral sacroiliitis)]. PMID- 1871477 TI - [What is your roentgen diagnosis?]. PMID- 1871478 TI - [Current knowledge about the progression of chronic kidney failure]. PMID- 1871479 TI - [Patient selection and efficacy of tumor after-care in surgically treated colorectal carcinoma]. AB - Scheduled follow-up after surgically treated colorectal cancer remains controversial because eventually only about 5% of patients profit from it. Careful selection should therefore spare those patients unnecessary investigations who are least likely to benefit from follow-up. Only patients should be considered whose tumor was completely resected and who were found free of distant metastases. These patients should be fully informed about their disease and accept scheduled investigation even if asymptomatic. A questionable operability with regard to a second surgical intervention forbids formal entry into a follow-up program as well as a decreased life expectancy due to other disease. The family physician is most qualified to carry out or coordinate these investigations. For the first two postoperative years intervals of three and for the further three years of six months are recommended. Physical examination and determination of CEA titers are the essential measures; colonoscopy, sonography, CT scans, chest X-ray, and for rectal cancer, endoluminal sonography are undertaken periodically. In such a selected cohort one can expect a resectable recurrence in 25% of patients, of which 20% can be cured. PMID- 1871480 TI - [Stress fractures]. AB - The clinical and radiologic picture of the rarely known stress fracture is illustrated by a case study of a calcaneus lesion. Two different aspects of the radiologic findings depending on localisation are demonstrated, and a third variant course without radiologic signs is postulated. It has to be emphasized that the typical stress fracture of the spongiosa has features that do not correspond to the common pictures of a fracture. It is, therefore, often overlooked in the beginning. A complete fracture can thus develop, necessitating a surgical stabilisation, i.e. of the head of the femur. Therefore, early diagnosis is essential. PMID- 1871481 TI - [Vegetative psychological syndrome]. AB - The common psychoautomatic syndrome nowadays represents the most frequently encountered disease. Since more than 20 years I use a scale of seven for all single psychic and somatic autonomic symptoms. I have termed 'autonomic psychosyndrome' the characteristic psychopathology associated with autonomic dysfunctions. This entity is the most common psychosyndrome. Its autonomic manifestations are linked to the actually prevailing 'Zeitgeist', devoid of eternity, immortality, God as well as divine foresight and reason. I perceive the cause of autonomic dysfunction as lack of faith and trust. The gift to believe, to trust adequately, is disturbed. Causal therapy consists in healing of this faithlessness and inability to trust. PMID- 1871482 TI - [Osteoporosis in Turner's syndrome]. AB - Axial and appendicular osteoporosis are common features of Turner's syndrome. The histology of this osteoporosis is similar in some respects to postmenopausal osteoporosis. Therefore, we treated a woman with Turner's syndrome who developed a vertebral wedge fracture, despite estrogen substitution since adolescence, with bone stimulating drugs. Absence of a beneficial effect on bone biological indices or bone mineral density, could be explained by other pathogenetic factors like a direct result of the chromosomal abnormality or other hormonal deficiencies. PMID- 1871483 TI - [Headache, hypertension]. PMID- 1871484 TI - [What is your diagnosis? Brucellosis]. PMID- 1871485 TI - [Is endoscopic subureteral injection therapy an alternative to conventional surgical therapy in vesico-ureteral reflux?]. PMID- 1871486 TI - [Can normal peripheral bone density measurements in osteoporotic spinal fractures be diagnostically significant?]. AB - In secondary osteoporosis, amazing etiologies can be found: We report on two cases of nonsecretory myeloma, which had been diagnosed by investigations for osteoporosis. In this connection the diagnostic value of bone-density evaluation by densitometry and high-resolution tomography is discussed and illustrated. PMID- 1871487 TI - [A case from practice (222). Essential hematuria]. PMID- 1871488 TI - [Laboratory quiz No.27]. PMID- 1871489 TI - [Bruxism in children and adolescents]. AB - It is important to know child bruxism symptomatology and etiology. It will allow diagnosis by simple endo and exo oral examination, in deciduous and mixte denture. Early treatment of bruxism can then be established, preserving integrity of permanent denture. PMID- 1871490 TI - [Calcified stylo-hyoid ligament. Its role in the diagnosis of laterocervical pain]. AB - The calcification of the stylo-hyoid ligament is very often accidentally discovered during a panorex examination. Sometimes it is responsible of lateral and cervical pain spreading to the oral cavity and the maxilla. This anatomic landmark results in man from the more or less complete ossification of the hyo branchial system due to the persistence of the Reichert cartilage. The anatomical environment of the ossified stylo-hyoid ligament is very rich in thick blood vessels and cranial nerves and can lead after compression or irritation to: vascular pain of the external carotid artery, recurrent syncopes by irritation of the carotid sinus, pain in the tonsils, phonation and swallowing troubles, referred pain in the temporo-mandibular joints. The standard clinical and radiographic examination will help to establish the differential diagnosis. The treatment is either non surgical, by cutaneous infiltration of local anesthetic or surgical, by the removal through the oral cavity of the calcified stylo-hyoid ligament. PMID- 1871491 TI - [Psychogenic oral paresthesia]. AB - Psychogenic oral paresthesia represent a proteiform condition, more and more frequent. The failure to recognize it can lead to unjustified investigations or/and procedures. These manifestations are secondary to a psychic problem which varies in severity. In most cases, the establishment of a trust relationship, explanations to the patient and eventually a psychotherapy are sufficient to eliminate the symptoms. In severe cases, a psychotherapy or a psychiatric treatment are almost always necessary. PMID- 1871492 TI - [Double blind clinical study of local immunotherapy in treatment of periodontal diseases]. AB - During a 3 weeks period, an immunotherapy by oral route was applied in patients presenting periodontal diseases (gingivitis and chronic adult periodontitis). This study, double blindly conducted, points out a statistically significative decrease of the main clinical symptoms of periodontal diseases (bleeding, erythema, oedema, pain, suppuration, fetidness) without any other local treatment and shows the interest of such a therapy in addition to the classical local treatments applied to patients presenting periodontal diseases. PMID- 1871493 TI - [Focus on post and cores]. AB - Inspite of the new technics using composite resin, cast dowel and core is still used to replace lost coronal structure of endodontically treated teeth. Before the core preparation, an X-ray is essential. The metal used for the post and core must be the same as the one used later for the following full crown. Preparation methods must be well established. Acrylic resin or silicone may be used as impression technics. PMID- 1871494 TI - [Computer-assisted design in removable partial dentures. Expert system and software for framework tracing]. AB - Stelligraph, a software program for designing the removable partial denture offers many possibilities in computer assisted technology. The design can be realized on any particular case, based on three different concepts. This software program can also provide on individual, manual and personalized design this offening complete freedom in the conception. This software program is an expert system in removable partial denture by providing the general practitioner with a rational design as well as clinical guidance for oral rehabilitation. PMID- 1871495 TI - [Dentistry and its remedies in the Netherlands during the 17th century]. AB - The XVIIth century is the Golden Century of Holland, liberated from spanish domination, and becoming an economical and political powerful State, owing to maritime trade. Art, Science and literature progress and shine as never equaled. Our investigation is based upon writtings of professors, and those of their students or any other practitioner newly established in Holland, land of liberty. In those writings we are in search of remedies against odontology. Usual therapeutics is all together general and local. General, its evacuated peccant humors by vein section and purgation; local, it acts upon surrounding regions (shoulder, tempel, ear, chin), in the mouth (collutorium), on the tooth or its cavity. PMID- 1871496 TI - [From embryogenesis to female phenotype in subjects with XY karyotype]. AB - On the basis of the findings of their investigation of the embryogenesis of the female genital tract, the authors advance a hypothesis concerning the origin of ambiguities between the genetic sex and the gonophoric sex which determine primary sexual characteristics observed in Morris' syndrome and in gonadoblastoma. According to the authors, in gonadoblastoma there is dysgenesis or even agenesis of the gonads, with a total absence of Sertoli cells and, therefore, no secretion of anti-Muller substance and this explains the development of the Muller canals into uterus and Fallopian tubes and the presence of a vagina in an XY subject. In the syndrome of the feminizing testis, XY subjects have testes containing Sertoli cells which have produced anti-Muller substance. However, the initiation of the production of this substance is delayed and it is this delay which has permitted the tendency towards feminization of the uro-genital sinus with the formation of a vagina. The authors thus refute the theory which holds that the Muller cells are involved in the genesis of the vagina. PMID- 1871497 TI - [Immunoradiometric determination of total and active renin in human fetal appendages]. AB - The total renin and active renin in human fetal appendices were determined by an immunoradiographic assay. In addition, some samples of maternal plasma were analyzed in order to provide a reference value. The prorenin level was determined by subtracting the level of active renin from that of the total renin. At the end of this study, it was found that the mean total renin concentration was 515 +/- 54 pg/ml in the peripheral blood of the woman who had given birth, 30,385 +/- 2,951 pg/g in the tissue of the chorion and 3,986 +/- 822 pg/g in the amnion. The level within the placenta reached 1,113 +/- 155 pg/g of tissue in the chorionic plate, 256 +/- 53 pg/g in the villosities and 294 +/- 46 pg/g in the basal plate. In these various tissues, prorenin accounted for over 80% of the total renin, except in the chorionic villosities, where it accounted for only 72.44%. In general, this study showed that the highest, concentrations of immunoreactive renin are found in the chorionic membrane. This membrane probably plays a decisive role in regulating the renin-angiotensin system within the fetal appendices. PMID- 1871498 TI - [Fetal cardiopathies. Balance of 7 years of consistent screening at the maternity unit of the Pontarlier hospital]. AB - The authors carry out a retrospective analysis of the cases of fetal heart disease reported in a maternity clinic since 1983. Sixty-nine percent of these cases were detected by ultrasound during pregnancy. There were no malformations in a fetus of the "high-risk" mother. The early care given to malformed neonates does not appear to have improved their vital and/or post-operative prognosis. Early diagnosis of serious malformations should lead to a greater number of voluntary terminations of pregnancy. PMID- 1871499 TI - [Doppler and reduction of perinatal mortality]. AB - The authors think that perinatal mortality can be substantially reduced by accurate evaluation of chronic fetal distress by means of ultrasonic biometry routinely applied to pregnant women at each consultation and a Doppler examination carried out whenever retardation is detected or in any abnormal situations which could lead to such retardation. The authors present their experience in 353 women followed-up in their Service. PMID- 1871500 TI - [Activities of a family planning clinic incorporated to a public medical service over a 4-year period]. AB - Over a period of four years, 1769 women, all of whom were married with at least 2 children, agreed to use an intra-uterine contraceptive device (IUD), 1199 women (predominantly unmarried) preferred to use an oral contraceptive (in most cases, two- or three-phase, low-estrogen pills) and 62 a local contraceptive (spermicide or diaphragm). The period of use was 89.65% for the IUDs, with a single case of acute inflammation of the genital tract. As expected, we diagnosed a large number of cases of asymptomatic Chlamydia trachomatis infections in 24% of the women using oral contraceptives and in 15% of the women fitted with an IUD. Symptomatic cases took the form of abdominal discomfort, vaginal discharge and metrorrhagia. In the opinion of the authors, the successful results obtained were due to the cooperation between the GP and the gynecologist and to a clear and firm policy towards the choice of the optimum method of contraception. In this article, the authors describe the principles behind this policy. PMID- 1871501 TI - [Uterine phlebography in pelvic venous stasis]. AB - Pelvic veins opacification is very helpful in the diagnosis of vascular pelvic pain. First applied to intrauterine vascularisation and hypoplasia research, hysterophlebography allow the venous side of stasis to be obvious. 1) Normally, a fine intra-parietal network draining in intrauterine peripheric vein (arcuate network) is patterned by the contrast medium. For that 4 vessels roots are leaving: 2 lumbo-ovarian pedicles joining uterine venous side und tubal veins and extending over lumbo-ovarian pedicle; 2 uterine pedicles resulting from 2 uterine veins and receiving vesical veins located in the base of broad ligament. Contrast medium empties very quickly and almost the whole uterus emptying is lasting less than 10 seconds. 2) From a pathological point of view: a) in stasis, intrauterine veins pattern features are: intra-parenchymatous pictures of dilated venous network, local alterations pictures often secondary to thrombosis (9/10 on the left side) with intra-parenchymatous stasis and oblique anastomatic main vessels characterizing uterine veins thrombosis, more than 20 seconds emptying delay. Hysterographic and phlebographic times take advantage to be paired by visualizing mucous lesions (hypoplasia and polyp. endocervical and corporeal) in intra parenchymatous stasis phenomena. b) Extrauterine stasis signs are characterized by preferentially right pedicles dilatation. Standing in upright position enhances stasis (proclive radiographies at 70 degrees). Dilatation is particularly located at the base of the broad ligament and gives to uterine veins with wide smeets a flexuous feature with wide contasted clusters. Hence here emptying is slow and belayed. PMID- 1871502 TI - [Achondrogenesis. Ultrasonic diagnosis and clinical and anatomopathologic comparison]. AB - The authors report two cases of achondrogenesis, the first of which was diagnosed in utero. Ultrasonographic abnormalities suggested the diagnosis, which was confirmed radiographically. The diagnosis of achondrogenesis in utero made it possible to avoid a Cesarian. It is always difficult to extract the malformed fetus. The histopathology findings make it possible to codify this rare type of congenital and lethal chondrodysplasia. Achondrogenesis is probably inherited in a recessive and autosomic fashion. PMID- 1871503 TI - [Hydranencephaly. Report of a new case]. AB - Hydranencephaly is the total or virtually total absence of the cerebral hemispheres, which are reduced to a membranous sac of glial tissue, with no ependymal coating, in an intact skull. This is rare disorder (0.5 per thousand births). It is classified as a circulatory encephalopathy. Two opposing theories are generally advanced: the encephaloclastic or destructive theory and the theory of dysontogensis or malformation, due to early disruption of organogenesis. It has many causes (vascular, viral, parasitic, genetic, toxic, estrogenic...). It appears to be readily diagnosed by ultrasound, the neurological findings may be normal at birth, but transillumination of the skull remains a simple and reliable diagnostic test. Transfontanellar ultrasound, CT scanning and anatomical confirmation alone can establish the diagnosis. The prognosis is hopeless and there is no treatment. PMID- 1871504 TI - [Post-menopausal endometriosis developed during tamoxifen treatment]. AB - The authors report a case of endometriosis (adenomyosis + endometrioma) which occurred in a female patient aged 69 years, who had undergone the menopause 15 years previously and who had been taking Tamoxifen for 7 years as an adjuvant treatment for cancer of the breast. Tamoxifen, a non-steroidal anti-estrogen derived from diethylstilbestrol, has a variable antagonist/agonist so that estrogenic stimulation of the female genital tract may occur, particularly of the endometrial mucosa. The reactivation of the endometriosic foci which had become quiescent under the impact of the natural menopause, which, by iatrogenic analogy is included in the series of paradoxical uterine effects of tamoxifen. PMID- 1871505 TI - How to manage with a profit motive. PMID- 1871506 TI - Zest anchors cast copings. PMID- 1871507 TI - Dental gold casting alloys--a review. PMID- 1871508 TI - Overcoming the negative effects of direct reflection in thin no room porcelain restorations. PMID- 1871509 TI - Tumor markers in human renal cell carcinoma. AB - Localization of tumor markers in human renal cell carcinomas (RCC) was studied by an immunohistochemical method using 12 different monoclonal antibodies (MAbs) recognizing carbohydrate antigens, and 2 polyclonal antibodies against S-100 protein and neuron-specific enolase (NSE), respectively. 115D8, DF3 and the MAb to epithelial membrane antigen (EMA) reacted with 9 of 13 (115D8), 6 of 13 (DF3) and 5 of 12 (MAb to EMA) cases of RCC, respectively. S-100 protein was also found in 10 of 13 cases of RCC. Further immunohistochemical studies showed that tumor cells of all 13 RCCs were strongly positive for NSE. Serum NSE levels of patients with RCC were examined by radioimmunoassay. This examination revealed that increased levels of NSE were detected in 11 of 17 sera of patients with RCC. Positive rates for patients in stages II, III and IV were 100% (10/10). On the other hand, increased levels of CA15-3 were detected in only 2 of 17 sera by enzyme immunoassay. Our results indicate that NSE may be a useful marker for human RCC, especially for those tumors that have broken through the renal capsule. PMID- 1871510 TI - Sublethal damage repair in two radioresistant human tumor cell lines irradiated as multicellular spheroids. AB - Melanoma and lung adenocarcinoma may be amenable for radiotherapy if it were possible to increase the presently used total dose. In order to investigate this, spheroids from two cell lines of human origin, one obtained from a BRO melanoma and one from an NCI-H125 lung adenocarcinoma were exposed to graded doses (3-9 Gy) of radiation with 18-MV photons. Radiation was applied either as a single dose or as split doses with an interval of 6 h to determine the extent of sublethal damage repair. Radiation response was quantified in terms of spheroid cure and specific growth delay. Both cells lines have previously been shown to be less sensitive than a neuroblastoma and a squamous cell carcinoma cell line grown as spheroids. Data obtained from the growth delay analysis were used to calculate the extent of split-dose recovery. Repaired dose for BRO spheroids did not increase after 7 Gy, whereas in NCI-H125, the repaired dose showed a steady increase. Recovery ratios did not differ between the two cell lines, but were lower than reported for normal tissues. Both cell lines revealed a low repair capacity was expressed by the beta-value of the linear-quadratic (LQ) equation. However, repair capacity for sublethal damage as expressed by the dose repaired and the beta-value of the LQ equation was not different from values reported earlier by us for neuroblastoma and squamous cell carcinoma when grown as spheroids. This indicates that the low radiosensitivity for the cell lines used in this study is determined by the alpha-value of the LQ equation. Our results support the clinical finding that the application of increased total radiation doses in the treatment of melanoma and lung adenocarcinoma may be feasible if radiation is applied in multiple small fractions to ensure normal tissue sparing. PMID- 1871511 TI - A monoclonal IgM antibody to a methylcholanthrene-induced tumor. 2. A biologically relevant glycoprotein antigen with a molecular weight of 40-43 kilodaltons. AB - We have recently described a monoclonal IgM antibody, H17, to a mouse methylcholanthrene-induced tumor with specificity for a common saccharide, namely alpha-N-acetylgalactosamine. Although recognizing a glycosidic determinant most likely to be part of many cell surface glycoproteins, H17 was highly specific for the immunizing tumor. This discriminatory ability was investigated by testing the antibody binding to a panel of normal and transformed mouse and human cells. Cross-linking studies showed that H17 reacts with a glycoprotein with a molecular weight of 40-43 kD, which through blockage during the process of immunization has an impact in vivo on tumor growth. Moreover, the uncommon sensitivity to complement-mediated lysis by this methylcholanthrene-induced tumor was blocked by the H17 monoclonal antibody. PMID- 1871512 TI - Cytochemical and immunocytochemical characterization of Yoshida ascites sarcoma cells. AB - Some cytochemical and immunocytochemical investigations were carried out on actively growing Yoshida ascites sarcoma cells. These cells displayed an intense granular alpha-naphthylacetate esterase (ANAE) staining while the alpha naphthylbutyrate esterase (ANBE) reaction was in part fluoride-sensitive and marked particularly in the large-size malignant cells. Acid phosphatase as well as peroxidase activities were not detected. The lack of immunoreactive lysozyme and alpha 1-antitrypsin suggested a poor differentiation of the above-mentioned tumor cells, but fibronectin and S-100 protein where highly expressed, as in tumors arising from the mononuclear phagocyte system. PMID- 1871513 TI - Identification and characterization of alkaline phosphatase isozymes in human colorectal adenocarcinomas. AB - Using alkaline phosphatase isozyme-specific immunocatalytical assays, the content of isozymes was determined in normal mucosas and adenocarcinomas from human colon or rectum. Tumor levels of both the tissue (liver)-unspecific and the placental like alkaline phosphatase (PLAP-like) were elevated compared to normal mucosas of the same patients. Such elevations have been reported previously, particularly in seminomas and ovarian tumors. In several tumors, moreover, the intestinal isozyme was expressed in lesser amounts than in the adjacent mucosa. The present results indicate that the activation of two of the phosphatase isozymes, including expression of the typical germ cell line phosphatase (the PLAP-like isozyme), may occur even in nongonadal tumors. This may reflect an induction pattern of phosphatase isozymes, with implications for malignant transformation also in other tumors. PMID- 1871514 TI - [Adult oligoarthritis with antinuclear factors. A new syndrome, relations with juvenile oligoarthritis]. AB - We report an original form of chronic inflammatory arthritis in 14 young adults, mainly females: an oligoarthritis with antinuclear antibodies. A first group of 10 patients, 9 females and one male, over 17 year-old, mean age 25, presented with monoarthritis or oligoarthritis of the knees, and less frequently of the wrist or elbow. Arthritis was chronic, recurrent, not destructive nor incapacitating. Rheumatoid factor was absent, and the only biologic abnormality was positive ANA at a significant rate. No patient was typed for HLA DR5. No other clinical or biological symptom appeared during a mean follow-up period of 5.5 years (6 mo-30 yrs). The patients have been totally free of any ocular symptoms. The benignity of the disease and its good prognosis must be underlined. Another group of 4 adult women had a similar inflammatory disease, which started during childhood: the biological and clinical spectrum was found quite similar in both groups, except for uveitis which occurred only in the later. Most subsets of juvenile arthritis have counterpart in adulthood, except for the pauciarticular subset with AAN. The cases herein described could fill the gap, the only difference with the juvenile onset form being the absence of uveitis. Thus, even if our observations of oligoarthritis with ANA in young women are the equivalent of the pauciarticular form in young girls, ocular involvement remains specific of childhood. PMID- 1871515 TI - [Therapeutic use of a monoclonal, anti-CD4 antibody in refractory rheumatoid polyarthritis. Preliminary results]. AB - Ten patients (6 women and 4 men), with a group mean age of 65 years, defined as severe and with a mean follow-up period of 9 years and refractory to conventional treatments, were treated with monoclonal anti-CD4 antibodies in an open study. The monoclonal antibodies, of murine origin, were administered by intravenous route for ten consecutive days at a dose of 10 mg (1 patient), 15 mg (2 patients) or 20 mg (7 patients). Local and systemic tolerability were excellent. Clinical improvement was rapid (pain, morning stiffness, Ritchie index, p = 0.005 between D0 and D15), as was the paraclinical improvement (C-reacting protein, p = 0.008), although without achieving complete remission. The outcome revealed that the effect was more prolonged in patients treated with 20 mg per day than in the others, suggesting a dose-effect relationship. The improvement obtained may persist for more than 9 months in some patients. No significant change in immunological parameters was found at the end of the treatment (lymphocyte populations, immunoglobulins, complement). Only 2 out of 10 patients developed anti-mouse antibodies. As a result of its excellent tolerability and rapid effectiveness, this antibody appears to offer fresh therapeutic prospects in rheumatoid arthritis. PMID- 1871516 TI - [Role of collagen conformation in type II anticollagen immunity in rheumatoid polyarthritis]. AB - Type II anticollagen (CII) autoimmunity is a frequently reported, but non specific, phenomenon in rheumatoid arthritis (RA). The authors show that in 88 sera samples from patients suffering from RA, the incidence of antibodies targeted against endogenous human CII was the same as that found for 149 control blood donors (14.8% versus 11.4%). However, a significant difference was found for the incidence of antibodies targeted against the alpha-chains of CII (26.1% versus 6.0%, p less than 0.001). As a result of investigating the specificity of the anti-CII antibodies in greater detail by means of an immunoprinting of the CII peptide fragments obtained after splitting the molecule by cyanogen bromide, the authors have demonstrated that the largest CII peptides (CB10 and CB11) were better recognized than the smaller peptides (CB8, CB9.7), with no significant difference between PR and control plasmas. Using competitive methods, evidence was obtained in support of heterogeneous recognition by the anti-CII antibodies: some recognize conformational determinants only, whereas others are targeted against the primary sequences of the alpha-1 (II) chain. PMID- 1871517 TI - [Cytogenetic anomalies after isotope synoviorthesis in rheumatoid polyarthritis]. PMID- 1871518 TI - [Clinical and epidemiological study of osteoarthritis of the hand. Based on 500 cases selected from a Health Examination Center]. PMID- 1871519 TI - [Costal osteoid osteoma. Apropos of a case. Review of the literature]. PMID- 1871520 TI - [Heart valve lesions in rheumatoid polyarthritis. Apropos of 2 cases]. PMID- 1871521 TI - [Immunological aspects of Behcet's disease]. PMID- 1871522 TI - [Controlled therapeutic trial of diclofenac in meniscectomy under arthroscopy]. PMID- 1871523 TI - [Spectacular effect of tiludronate in osteoporosis circumscripta cranii]. PMID- 1871524 TI - [Arthropathy of the fingers in hemodialyzed patients with chronic renal failure. Apropos of a study of 44 patients]. AB - Arthropathy affecting the small joints of the hand are one of the osteo-articular complications of chronic renal failure treated by hemodialysis. Amongst the 44 patients studied, there were 9 cases of arthropathy of the fingers. The clinical characteristics (age, duration of hemodialysis) and paraclinical characteristics (oxygenated free radical activity indicators, serum levels of aluminium and beta 2-microglobulins) appear to be specific to this population and may help us to understand the pathogenesis of the joint lesions. PMID- 1871525 TI - [Prevalence of secondary Gougerot-Sjogren syndrome in Northern Africa]. PMID- 1871526 TI - [Fibrous finger cushions. Possible role of barbiturates]. PMID- 1871527 TI - [Pneumocystosis in dermatopolymyositis treated with low-dose methotrexate]. PMID- 1871528 TI - [Exsudative synovitis and periosteal apposition. An uncommon rheumatic manifestation of adult chondroblastoma]. PMID- 1871529 TI - Radix paramolaris in permanent mandibular molars: identification and morphology. AB - The Royal Dental College, Copenhagen, houses an extensive collection of human teeth which have been extracted in Denmark. The collection presently includes 203 permanent mandibular molars with a root complex containing a facially-located supernumerary root. This macrostructure is named radix paramolaris (RP). By analyzing the large number of specimens available it was possible to establish uniform and precise criteria for the identification of RP on M1 inf, M2 inf, and M3 inf. The analyses included both separate and non-separate RP. The representation of the RP variants according to tooth type was mapped. Furthermore, the following clinically relevant variables with respect to RP were registered: degree of separation, divergence, apical bend, apical gracility, and fusion. Because of the nature of the material, the study was mostly qualitative and non-metric. The results are aimed primarily at clinical dentists, dental morphologists, and dental anthropologists. PMID- 1871530 TI - Morphometric analysis of occlusal groove-fossa-system in mandibular third molar. AB - Based on serially cut 200-microns-thick sections from 21 human mandibular third molars, a quantitative characterization was made of the morphology in the mesial and distal interlobal groove. Two parameters were used: depth of interlobal groove and structure angle. The interlobal groove depth varied between 0.13 and 0.55, taken in relation to the maximum crown height. The structure angle varied between 2 degrees and 170 degrees. If the structure angle was less than or equal to 25 degrees, the interlobal groove was classified as a fissure; if the angle was greater than 25 degrees, the interlobal groove was classified as a groove. Only in 18% of the sections did the interlobal groove manifest itself as a fissure. The study demonstrates that it was possible unambiguously to describe the two-dimensional profile of interlobal grooves by groove depth and structure angle. PMID- 1871531 TI - Saliva composition and caries development in asthmatic patients treated with beta 2-adrenoceptor agonists: a 4-year follow-up study. AB - In an earlier study, we found that chronic treatment with beta 2-adrenoceptor agonists in asthmatic subjects gave an impaired saliva secretion and a higher caries prevalence than in healthy controls. Twenty-one of the asthmatics and their matched controls were examined 4 yr later in a follow-up study. Samples of whole saliva stimulated by chewing and parotid saliva stimulated by citric acid were collected and dental caries was scored. In the asthmatic group the secretory rates of stimulated whole and parotid saliva decreased by 20% and 35%, respectively, compared to the control group. The number of lactobacilli increased. The asthmatic subjects had a decreased output per minute of total protein, amylase, hexosamine, salivary peroxidase, lysozyme, secretory IgA, a bacteria-aggregating glycoprotein, potassium, and calcium in stimulated parotid saliva. Initial and manifest caries lesions as well as the number of DFS were significantly increased in the asthma group. We conclude that asthmatic patients treated with beta 2-adrenoceptor agonists have an increased caries susceptibility due to an impaired saliva secretion caused by the use of beta-adrenergic agonists. PMID- 1871532 TI - Temporalis and masseter muscle activity in patients with anterior open bite and craniomandibular disorders. AB - Activity in temporalis and masseter muscles, and traits of facial morphology and occlusal stability were studied in 22 patients (19 women, 3 men; 15-45 yr of age) with anterior open bite and symptoms and signs of craniomandibular disorders. Facial morphology was assessed by profile radiographs, occlusal stability by tooth contacts, and craniomandibular function by clinical and radiological examination. Electromyographic activity was recorded by surface electrodes after primary treatment with a reflex-releasing, stabilizing splint. Maximal voluntary contraction was reduced compared to reference values, particularly in subjects with muscular affection, but maximal activity increased significantly when biting on the splint. Maximal voluntary contraction was positively correlated to molar contact and negatively to anterior face height, mandibular inclination, vertical jaw relation and gonial angle. Relative loading of the muscles was markedly increased during resting posture. It was concluded that reduced occlusal stability and long-face morphology were associated with weak elevator muscle activity with disposition overload and tenderness. The results also indicated that increase of occlusal stability might lead to increased muscle strength and possibly reduce risk of physical strain. PMID- 1871533 TI - Incidence of adverse effects of dental materials. AB - Acute and long-standing adverse effects from dental materials used in the treatment of 13,325 patients in 15,820 appointments were recorded by 137 dentists. Twenty-four suspected side effects were reported by the patients and 22 by the clinicians; 7 were classified as "probable" or "possible" acute reactions and 15 as long-standing effects, 13 being "verified" and 2 "probable". In another survey, 31 dentists representing a total of 387 years of practice recollected 113 patients with side effects from dental materials. PMID- 1871534 TI - Fluoride release and uptake by glass ionomers. AB - The aim was to study the fluoride release 1) from 7 and 15-month-old glass ionomer specimens after treating them with fluoride; 2) from fresh compared with matured material; and 3) from specimens stored for 29 months in running water. Glass ionomer test specimens which had been in running water for first 7 then 15 months were treated with a 50 ppm fluoride solution after which the specimens were again exposed to running water for first 24 h and then 1 wk. The fluoride release was measured after each of the two periods of time. The fluoride treated specimens released more fluoride than the nontreated ones. This effect was not observed with composite resin specimens which were studied for comparison. Fluoride release from fresh glass ionomer specimens was observed to be 3-10 fold compared to specimens that had matured for 3 days. The release of fluoride from specimens that had been in running water for 29 months was measured and the results were compared with those of earlier measurements. It was found that the release reached a constant level for all tested glass ionomers during the second year. PMID- 1871535 TI - Area ratio effects on metal ion release from amalgam in contact with gold. AB - The effect of area ratio, chloride concentration and brushing on amalgam in contact with gold was studied by measuring the amounts of elements released in the electrolyte. A type III gold alloy was stored for 4 months in contact with a conventional amalgam, area relations 6/1 and 6/3, in an electrolyte containing 85 mM NaCl with 10 mM phosphate buffer. A specimen with area relation 6/1 was also stored in a 10 mM NaCl solution with 10 mM phosphate buffer. The solutions were renewed each month and analyzed for Cu, Zn, Sn, Hg, and Ag in an atomic absorption spectrophotometer. Cross-sections of the amalgams were studied in a scanning electron microscope. The tendency for Sn and Cu to be released from the amalgam was greater than for the other elements. The Sn-release probably mainly originated from surface corrosion and Cu-release from subsurface corrosion. A stronger galvanic influence enhanced only the release of Cu, and to a less extent Zn. The subsurface corrosion of the amalgam and increasing release of Cu was, in contrast to the other elements, largely dependent on a high chloride concentration in the electrolyte. Light brushing of the specimens had no effect on the amounts of elements released. PMID- 1871536 TI - Marginal fit of porcelain and indirect composite laminate veneers under in vitro conditions. AB - The purpose of the present study was to compare the marginal adaptation of indirect composite and porcelain veneers in vitro using transmitted-light microscopy. A preparation with a marginal chamber finish for a veneer was performed on 10 extracted molars after which 5 composite and 5 porcelain veneers were made and fitted using self- and light-cured microfill composite resin. Three longitudinal and 3 horizontal sections were cut in each preparation with the light microscope. Although the absolute marginal discrepancy at the cervical location had the highest statistical significance in the composite veneer group, the composite and porcelain veneers, in general, demonstrated a similar absolute marginal discrepancy and thickness of luting agent with average values from 50 microns to 195 microns for the two parameters. A considerable amount of excess of luting agent was furthermore observed in both groups of veneers, being most pronounced in the composite veneers. PMID- 1871537 TI - Gastro-oesophageal reflux and severity of pulmonary disease in cystic fibrosis. AB - The correlation between oesophageal dysfunction (OD), pathologic gastro oesophageal reflux (GOR), and severity of pulmonary disease was studied in 12 patients with cystic fibrosis (CF). They were interviewed about symptoms of OD and underwent 24-h pH recording in the oesophagus, oesophageal manometry combined with reflux provocation tests, the acid perfusion test, the acid clearance test, lung function tests, and scoring of the chest radiograph. Six of the 12 patients reported symptoms of OD. Abnormal GOR, as shown by 24-h pH monitoring of the oesophagus, was found in eight of them. Altogether 9 of the 12 participants had at least one pathologic oesophagus test result. Results of radiologic examinations of the oesophagus, performed in six patients, were pathologic. The four patients with the best chest radiograph scores and the best lung function had significantly less signs and symptoms of OD and GOR than the other eight patients. We conclude that OD, GOR, and pulmonary disease covariate in CF. PMID- 1871538 TI - A new method for evaluating gastric ulcer healing by endoscopic ultrasonography. AB - We observed the quantitative estimation of the transmural changes associated with gastric ulcer healing by using endoscopic ultrasonography (EUS). It was possible to diagnose the depth of ulcer by EUS. Forty-eight patients were divided into three treatment groups. Group A (n = 16) was treated with 800 mg cimetidine daily, group B (n = 22) with 20 mg omeprazole daily, and group C (n = 10) with 400 mg cimetidine + 300 mg gefarnate daily. EUS was performed before and after 2, 4, and 8 weeks of treatment. The groups were compared from the viewpoints of endoscopic findings and contraction rate of the length and the cross-sectional area of the ulcer in EUS pictures. The best healing of both the endoscopic and EUS findings was seen in group B. By estimating the changes inside the ulcer, EUS may provide useful information for choice of anti-ulcer agents. PMID- 1871539 TI - The endoscopic Doppler: its value in evaluating gastroduodenal ulcers after hemorrhage and as an instrument of control of endoscopic injection therapy. AB - In this prospective study of 80 patients with active bleeding from the gastrointestinal tract a Doppler ultrasonographic investigation of the gastroduodenal ulcers was performed, in addition to immediate endoscopic examination. Admitted to this study were ulcers with the stigmata of acute bleeding, such as a visible blood vessel in the ulcer floor, a blood clot, or a black base and Forrest III lesions. In 52 patients Doppler ultrasonography was able to document unequivocally a superficial blood vessel. Complete agreement of endoscopic and Doppler results was obtained in only 49% of the cases. When a blood vessel was positively identified, local injection of epinephrine and polidocanol was carried out. Thereupon, in the further course, the acoustic signal was shifted into deeper regions or disappeared entirely. In 8% of the cases initial sclerosing was followed by a rebleed, which was again treated by injection therapy. None of the patients died of their GI hemorrhage. Endoscopic Doppler ultrasonography is a new and effective procedure that enables objectification of the endoscopic findings. It identifies the indication for proceeding to operative endoscopy and can monitor the effectiveness of the latter. PMID- 1871540 TI - Treatment of postoperative paralytic ileus with cisapride. AB - The effect of cisapride on postoperative colonic motility was studied in 40 patients undergoing cholecystectomy under randomized, double-blind conditions. The patients received 10 mg of cisapride or placebo by intravenous injection starting on the day of surgery and repeated every 12 h until the 3rd postoperative day. The return of propagative motility in the colon was visualized by means of radiopaque markers and serial abdominal radiographs. Cisapride induced a significantly earlier return of propulsive motility in the right colon, as indicated by the propagation of markers from the ascending colon to the transverse colon (p less than 0.05). Radiopaque markers reached the descending colon (p less than 0.05) and the rectosigmoid colon (p less than 0.05) significantly earlier in the cisapride group than in controls. The first passage of feces occurred significantly earlier in cisapride-treated patients than in controls (p less than 0.05). The first passage of gas after surgery did not differ significantly between the groups. Our results suggest that cisapride can be used to induce earlier return of propagative motility in the colon after major abdominal surgery. PMID- 1871541 TI - Failure of sucralfate in the treatment of refractory esophagitis versus high-dose famotidine. An endoscopic study. AB - Scarce data exist on the medical treatment of patients with peptic esophagitis who are non-responders to conventional or higher doses of H2-blocker agents, and no controlled trial on such patients has been published so far. We conducted a randomized single-blind study on the effects of 1 g sucralfate four times daily (n = 8), a mucosa-protective agent, versus 40 mg famotidine twice daily (n = 8), a new H2-blocker agent, administered for 12 weeks, in the treatment of peptic esophagitis (grades I to IV in accordance with Savary and Miller) refractory to a 6-month therapy with ranitidine at a dosage of 150 or 300 mg twice daily. Complete healing of the esophageal lesions was observed in none of eight patients receiving sucralfate, as compared with five of eight taking famotidine (p less than 0.05, Fisher exact test). Three of eight patients treated with sucralfate and three of eight with famotidine had complete disappearance of symptoms, whereas improvement was observed in two and three of eight, respectively (p less than 0.05 in both cases). We conclude that anti-secretory therapy is more effective than mucosal protection in the treatment of refractory peptic esophagitis. PMID- 1871542 TI - The incidence of Crohn's disease is not decreasing in Sweden. AB - An epidemiologic study of the incidence of Crohn's disease during the 25-year period 1963-1987 within a geographically well defined area has been performed. The mean annual incidence during the 25 years was 6.1/10(5) inhabitants. During the first quinquennium the incidence was 4.3/10(5) inhabitants, but during the next four quinquennia the incidence was very stable around 6.6/10(5) inhabitants. The point prevalence on 31 December 1987 was 146/10(5), with a male to female ratio of 1:1.15. An analysis of birth cohorts could not reveal any cohort more prone to develop the disease. Of the 246 incidence cases 5 patients had died of Crohn's disease. The percentage of small-bowel disease only was very stable during the whole study period. The proportion of large-bowel disease decreased only slightly, and combined small- and large-bowel disease increased somewhat towards the end of the study period, probably because of better diagnostic methods. PMID- 1871543 TI - Partial deficiency of alpha 1-antichymotrypsin is associated with chronic cryptogenic liver disease. AB - alpha 1-Antichymotrypsin (ACT) and alpha 1-antitrypsin (AAT) are two closely related antineutrophil proteinase inhibitors. Whereas AAT deficiency is clearly linked to liver disease, an association between liver disease and partial ACT deficiency has not been established. In a previous study we noted an increased prevalence of liver abnormalities among subjects with heterozygous ACT deficiency. To study a possible association between partial ACT deficiency and liver disease, we screened 316 consecutive patients with biopsy-verified liver disease for partial ACT deficiency and compared the prevalence with that of an unselected adult population in a case-control study. In all, 9 of 316 patients had partial ACT deficiency, which is more than expected (prevalence ratio (PR), 2.46 (1.15-5.27), P less than 0.05). The prevalence of partial ACT deficiency was highest in the chronic active hepatitis (5 of 40; PR, 12.0 (5.33-27.0] and the cryptogenic cirrhosis (3 of 24; PR, 12.0 (4.38-32.9] subgroups. In the chronic active hepatitis subgroup two patients (PR, 8.16 (2.25-29.5] were ACT deficiency heterozygotes, thus partly explaining the high prevalence of partial ACT deficiency among patients with chronic liver disease. The majority (6 of 9) of the patients with partial ACT deficiency lacked autoimmune and viral markers and were thus cryptogenic. The present findings show that partial ACT deficiency and chronic cryptogenic liver disease are associated. To some extent (the true magnitude of which is at present unknown) partial ACT deficiency is caused by a rare trait, heterozygous ACT deficiency, which in parallel with heterozygous alpha 1-antitrypsin deficiency (PiMZ) also seems to be associated with chronic cryptogenic liver disease. PMID- 1871544 TI - Mechanism of ursodeoxycholic acid- and canrenoate-induced biliary bicarbonate secretion and the effect on glucose- and amino acid-induced cholestasis. AB - The mechanism of ursodeoxycholic acid (UDCA)- and canrenoate-induced bicarbonate choleresis was studied before and during the administration of glucose or amino acids in anaesthetized pigs. Previous studies have shown that the canalicular secretion has, on a molar basis, a relationship among the secretion of chloride, bicarbonate, and bile acids of 0.9, 0.3, and 1, respectively. Ductular secretion is associated with the transport of 0.25 mol chloride per 1 mol bicarbonate. In control experiments UDCA was associated with a biliary secretion of about 1.3 mol chloride and 0.5 mol bicarbonate per 1 mol bile acid, and canrenoate caused the secretion of 1.2 mol chloride per 1 mol bicarbonate. Intravenous infusion of glucose or amino acids increased these relationships, and after administration of UDCA or canrenoate, these relationships were still increased by at least 70% on average when compared with the control experiments. A reduction in bile secretion after glucose or amino acid infusion is opposed by UDCA or canrenoate. The effect of UDCA or canrenoate on bile secretion is not disturbed by glucose or amino acids. Both substances stimulate canalicular bicarbonate secretion and could be of importance in improving cholestatic conditions. PMID- 1871545 TI - Selective inhibition of duodenal and jejunal villous cell alkaline phosphatase by the duodenal ulcerogen cysteamine. AB - We have found that cysteamine-HCl, a potent duodenal ulcerogen, after a single subcutaneous injection (30 mg/100 g body weight), inhibited villous cell duodenal and jejunal alkaline phosphatase (APase) under in vivo and under in vitro conditions. The duodenal and jejunal crypt-cell APase was not susceptible to cysteamine inhibition. Ileal APase from both the villous and the crypt cells was unaffected by cysteamine. Tissue-nonspecific APase from the kidney and liver was not affected by cysteamine either. The differences in tissue and cellular accumulation of cysteamine, the submolecular differences in APase molecules, and its anatomical localization in mucosal cells along the small intestine could explain the different degrees of susceptibility to cysteamine inhibition. The extent of duodenal APase inhibition by cysteamine was highly pH-dependent and varied from 5% to 85% within a pH range of 7.5-10.5. A shift in pH optimum from 9.6 to 9.3 was found in the presence of cysteamine. The inhibition of duodenal villous cell APase was greatly dependent on cysteamine concentration (Ki = 2.65 mM). At a fixed concentration of cysteamine it was not influenced by substrate concentration. Cysteamine did not change the Km value for duodenal APase but did decrease its Vmax to 46% and 15% of the controls when added in the assay or injected subcutaneously, respectively, indicating that the inhibition was of the linear, 'noncompetitive' type. Somehow cysteamine increased the requirement in the activation energy for substrate hydrolysis as well. The data indicate that macromolecular transformations could take place in the mucosal cells of duodenum after cysteamine administration. PMID- 1871546 TI - Factors influencing the release of cholecystokinin induced by gastrin-releasing peptide in man. AB - We have studied the basal release of cholecystokinin (CCK) and the CCK response to gastrin-releasing peptide (GRP) in man. GRP infusion was followed by a substantial and immediate release of CCK. Pancreatico-duodenectomy or antrectomy with or without duodenal exclusion or antrectomy with truncal vagotomy did not significantly change the basal release of CCK or the GRP-induced CCK release. These results indicate that both basal and GRP-induced release of CCK predominantly originate from the small intestine below the duodenum and the upper part of the jejunum and is unchanged by duodenal exclusion and vagal denervation of the small intestine. PMID- 1871547 TI - Best-buy regimen of ursodeoxycholic acid for patients with gallstones. AB - Bedtime administration has been advocated as a strategy for reducing minimum effective dose, side effects, and costs of chenodeoxycholic acid treatment of cholesterol gallstones, but little information is available for ursodeoxycholic acid (UDCA). We prospectively determined the minimum effective dose of bedtime UDCA in 44 patients with radiolucent gallstones treated with a range of UDCA doses (4.6-17.0 mg/kg/day). The average minimum effective dose for reducing the cholesterol saturation index (SI) of gallbladder bile to a value of 0.8 was 8.4 mg/kg/day for bedtime UDCA. The greater potency of the bedtime regimen was confirmed in seven individual patients by comparison with a mealtime regimen. Cholesterol SI was reduced from 1.25 during placebo to 0.73 during 7 mg/kg/day for bedtime UDCA and to 0.81 during 10 mg/kg/day for mealtime UDCA. The effect of the bedtime regimen was not enhanced by a repeated-release tablet formulation of UDCA by comparison with UDCA in 15 patients. We conclude that the bile acid dose is reduced during bedtime UDCA administration by comparison with mealtime UDCA in individual patients and that the best-buy regimen is 8.4 mg/kg/day UDCA given at bedtime for patients with gallstones as a group. With this dose, gallstone dissolution can be supported by unsaturated gallbladder bile at minimum risk of dose-related side effects and at minimum treatment costs. PMID- 1871548 TI - Side effects and complications after hepatic artery embolization in the carcinoid syndrome. AB - Twenty patients with histologically verified carcinoid liver metastases underwent a total of 24 liver artery embolizations by means of interventional radiologic techniques. There were no deaths. The postembolization syndrome, consisting of fever, abdominal pain, nausea, and vomiting, occurred in all the patients. Severe complications were rare, the most serious being multiple hepatic abscesses with septicemia in one patient, septicemia in another, and mild acute pancreatitis in a third. All these three patients recovered without any sequels from the embolization, and none required surgical intervention. The hepatic abscesses were drained percutaneously, guided by ultrasound. Hepatic artery embolization seems justified in patients with disabling symptoms from the carcinoid syndrome, as long as alternative therapy with the same benefit but fewer complications is not available. PMID- 1871549 TI - The effects of atropine or benzilonium on pelvic pouch and anal sphincter functions. AB - Anticholinergic drugs are used on an empirical basis for treatment of functional disturbances after restorative proctocolectomy, but their mode of action on ileal pouch performance is mainly unknown. We studied the acute effects of atropine or benzilonium on pouch characteristics and anal sphincter function in 20 patients with a pelvic pouch. Pouch volume was increased by 27% by atropine at distension with 20 cm H2O (p less than 0.01). Benzilonium tended to have a similar effect, but the changes did not reach statistical significance (p = 0.06). Pouch contractility, as reflected by volume fluctuations and pressure changes during distension, was almost abolished by both drugs. Sensory thresholds for sense of filling and, particularly, urge were raised. Resting anal pressure was slightly lowered, whereas no significant effect was found on maximal squeeze pressure. In conclusion, anticholinergics appear to have specific properties of action on small-intestinal reservoirs, constituting possible explanations for the empirically observed beneficial effects of anticholinergic treatment of functional disturbances after restorative proctocolectomy. PMID- 1871550 TI - High vasoactive intestinal polypeptide plasma levels in patients with Barrett's esophagus. AB - We have evaluated the correlation between vasoactive intestinal polypeptide (VIP) plasma concentration and severity of gastroesophageal reflux in patients with Barrett's esophagus and the possible differences in the VIP values of these patients compared with healthy volunteers. We also evaluated the relation between VIP plasma concentration and lower esophageal sphincter (LES) pressure in 24 patients with Barrett's esophagus. The mean VIP plasma concentration in 14 patients with severe gastroesophageal reflux was 25.6 +/- 0.75 pg/ml, significantly higher than the mean value observed in 10 patients with moderate reflux (18.9 +/- 0.67 pg/ml) (p less than 0.01). The mean LES resting pressure was significantly lower in the group of patients with severe gastroesophageal reflux than that observed in patients with moderate reflux (3 +/- 0.64 and 10.3 +/- 0.69 mm Hg, respectively; p less than 0.01). The mean VIP plasma concentration in 11 healthy volunteers (20.6 +/- 0.65 pg/ml) was significantly lower than the mean value observed in the subgroup of patients with severe gastroesophageal reflux (p less than 0.01). VIP values in patients with moderate reflux were not significantly different from those observed in our volunteers. There was a significant correlation between LES pressure and VIP plasma level (r = -0.9253; p less than 0.01). In conclusion, it is possible that the decreased LES resting pressure observed in patients with Barrett's esophagus and severe gastroesophageal reflux may be due to impairment of the VIPergic innervation, resulting in an increased local VIP release with possible overflow to peripheral plasma. PMID- 1871551 TI - Cytogenetic studies of prostatic cancer. AB - In this study we wanted to find out if the size or position of the constitutive C band positive heterochromatin regions of chromosomes was associated with variation in prostatic cancer predisposition. We found no such association when comparing the whole patient group with healthy controls, but younger (less than 70 years) cancer patients had significantly higher frequencies of large C-bands on chromosomes 1 and 16 than older patients (greater than 70 years). This could indicate a possible relationship between the amount of constitutive heterochromatin on chromosomes 1 and 16 and susceptibility to early development of prostatic cancer. The purpose of this study was to examine if the number of AgNORs was higher in malignant than normal or hyperplastic prostatic tissue, and if the number of AgNORs increased with increasing grade of malignancy. More AgNOR dots were found in the prostatic adenocarcinomas (average 24/cell) than in the normal and hyperplastic prostates (average 13/cell). The poorly differentiated adenocarcinomas had more AgNORs than the moderately and well differentiated cancers. The data indicate that analysis of silver staining-positive material in intact interphase cells may help distinguish between benign and malignant prostatic tumors, and between highly malignant and low malignant carcinomas. The purpose was to find consistent and specific chromosome abnormalities in primary prostatic adenocarcinomas. Because then existing techniques for culturing human neoplastic prostatic tissue rarely yielded sufficiant epithelial cell growth and mitosis we decided to modify these techniques. Tumor samples from 82 patients were processed for short-term culture. Cytogenetic analysis was successful in 57 tumors, 42 of which were cultured after September 1, 1988, when the modifications were implemented. Thirteen of the 15 primary tumor samples that contained clonal karyotypic abnormalities were processed after September 1, 1988. Loss of chromosomal material from 7q, 8p, and 10q, and structural aberrations of bands 7q22 and 10q24 were the most common aberrations found. From these data it may be inferred that both loss of tumor suppressor genes and activation of oncogenes located in the breakpoint regions may be important pathogenetic events in the development or progression of prostatic adenocarcinoma. In this study we wanted to examine the clinical implications of karyotypic abnormalities. We found a significant difference in survival after diagnosis and surgery between patients whose tumors had clonal structural abnormalities (A), patients whose tumors had nonclonal changes (NA), and patients whose tumors had normal karyotypes only (N).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1871552 TI - Prostatectomy in Denmark. Regional variation and the diffusion of medical technology 1977-1985. AB - In many countries prostatectomy is one of the most common surgical operations in elderly men. We used administrative data for the entire male population of Denmark to study temporal and regional variations in the use of prostatectomy from 1977 to 1985. The total annual number of prostatectomies increased by 43% during the period, when the transurethral procedure (TURP) gradually replaced traditional open surgery. TURP accounted for 56% of all operations in 1977 but increased its share to 92% in 1985. Substantial regional variations occurred with index values for prostatectomy in 72 recruitment areas ranging from 0.56 to 1.62 (SCV x 100 = 5.3). The amount of variation decreased during the process of technology diffusion, but remained at a relatively high level (as in other countries) even after the process had been completed (SCV x 100 = 5.1). PMID- 1871553 TI - Prostatic cancer in Aust-Agder County, Norway. Age, stage, grade and mode of presentation. AB - Two hundred and five patients (89 per 100,000 men) with newly diagnosed prostatic cancer comprises all cases in the Aust-Agder County in Norway over a 5-year period. There were 36% stage T0 M0, 19% T1-2 M0, 16% T3-4 M0 and 29% T0-4 M1. In patients with well differentiated disease (G1), 8% had distant metastases on presentation, whereas in the moderately differentiated tumors (G2) and the poorly differentiated tumors (G3) distant metastases occurred in 30% and 62%, respectively. A statistically significantly higher proportion of well differentiated (G1) tumors were observed in the younger age groups (less than 70 years). On presentation diagnosis was suspected on routine digital rectal examination in 9% of the patients, while 12% had symptoms on disseminated disease as mode of presentation. Of patients operated upon for apparently benign hyperplasia 13% had prostatic cancer. PMID- 1871554 TI - Presentation and clinical course of patients ultimately succumbing to carcinoma of the prostate. AB - Ninety-six patients who expired due to carcinoma of the prostate were identified within the primary treatment area of Brooke Army Medical Center between the years of 1981 and 1988. Although 71 patients were noted to have abnormal prostate examinations at the time of diagnosis, 11 had been noted to have a palpably normal prostate within three years of tumor diagnosis. Twenty-four patients had a palpably normal prostate at the time of diagnosis. Fifteen patients had been previously noted to have an abnormal prostate but biopsy in 11 of these had been benign. These data suggest that digital rectal examination of the prostate will not detect a number of patients who will ultimately die of carcinoma of the prostate. PMID- 1871555 TI - Blood ammonia concentrations resulting from absorption of irrigating fluid containing glycine and ethanol during transurethral resection of the prostate. AB - In 30 patients the blood ammonia concentration was measured 30 min was after transurethral resection of the prostate during which absorption of irrigating fluid containing 1.5% of glycine and 1% of ethanol had been indicated by serial expired breath tests. The volume of irrigating fluid that had been absorbed was either measured volumetrically (n = 25) or estimated from the ethanol concentration in the expired breath (n = 5); the median volume of irrigating fluid absorbed was 1.3 litres (range 0.2-4.3). There was no consistent rise in the blood ammonia concentration, nor was there any correlation between the blood ammonia concentration and the volume of irrigating fluid absorbed. No patient developed symptoms that could be clearly related to hyperammonaemic glycine toxicity, but 18 of the 30 patients developed other signs of the "TURP syndrome". The present results suggest that irrigating fluid containing both glycine and ethanol does not significantly increase blood ammonia concentration or produce symptoms of glycine toxicity. PMID- 1871556 TI - Vasopressin and cortisol levels in response to glycine infusion. AB - The plasma vasopressin and serum cortisol concentrations were recorded in 7 healthy volunteers receiving an intravenous infusion of 1 l of isosmotic (2.2%) glycine solution during 20 min. The infusion elicited a significant increase in the plasma vasopressin level by a mean of 60% (SEM 13) above baseline level. The serum cortisol level increased only in the patient who developed signs of glycine toxicity. These results suggest that a glycine solution has water-retaining properties by stimulating the vasopressin secretion but usually not by increasing cortisol secretion. PMID- 1871557 TI - Bacteriological findings in urine specimens from women. Association with urinary tract symptoms and sampling methods. AB - Urine sampling techniques were recorded in 147 women who brought a sample of urine voided at home to the general practitioner's surgery. Seventy-two women had lower urinary tract symptoms, and 75 had no symptoms at all. Eighty-nine (61%) had taken a midstream specimen, 77 (52%) had cleansed the periurethral area, and 15 (10%) had held the labia apart during micturition. Combinations of these techniques were used by 71 women while 40 (27%) had used no specific technique. The bacterial content of the urine (defined as the number of different bacterial strains found) was not reduced by either cleansing or by taking a midstream specimen, but it was significantly reduced in the women who had held the labia apart during voiding (p less than 0.05). Urine samples from women with symptoms had significantly lower bacterial content than those from patients who were free of symptoms (p less than 0.01). Women should be encouraged to ensure the free flow of urine by holding the labia apart during urine sampling. PMID- 1871558 TI - Prediction of T1-2 GI-II transitional cell bladder cancer; evaluation by histoquantitative methods. AB - A retrospective clinicopathological study was done including 175 T1-2 GI-II bladder cancer patients who all had transurethral resection or electrocoagulation as their initial treatment. Using interactive morphometry mean nuclear area (NA), mean standard deviation of nuclear area (SDNA) and the mean area of the 10 largest nuclei (NA10) were measured in the biopsies from primary tumours. The volume corrected mitotic index (M/V index) was estimated in the same sections. The histological grading was done according to WHO and clinical staging according to UICC. Progression in bladder cancer was observed in 36 cases. The progression (T-category) was related to M/V index (p = 0.0039), non-papillar growth (p = 0.0249), histological grade (p = 0.0736) and SDNA (p = 0.1535) in that order. In a separate analysis of papillary tumours NA10 showed predictive value (p = 0.0805) in addition to M/V index (p = 0.0067). Twenty-one patients died of bladder cancer and NA (p = 0.0069) as well as M/V index (p = 0.0984) predicted survival whereas other parameters had no substantial prognostic value. In a separate analysis of papillary tumours NA (p = 0.0209) and M/V index (p = 0.0402) predicted survival. The recurrence rate or recurrence-free period could not be significantly related to histological parameters. The results suggest the use of these morphometric features in place for histological grading in prediction of T1 T2 bladder tumours. In addition the results suggest the use of more aggressive therapy and more intensive follow-up programs for rapidly proliferating tumours as expressed by high mitotic activity. PMID- 1871559 TI - Bacillus Calmette-Guerin treatment of 39 patients with superficial transitional cell carcinoma of the bladder. AB - The effect of intravesical Pasteur-F strain Bacillus Calmette-Guerin (BCG) on bladder carcinoma was studied in 39 patients. Multiple recurrent superficial transitional cell carcinoma was present in 36 cases, including 11 with concomitant carcinoma in situ (CIS), and primary CIS in three. The mean age of the 27 men and 12 women was 72 years. A 6-week induction course was given, beginning usually 4-6 weeks after transurethral tumor resection (TUR) or random biopsies, with periodic followup cystoscopies and cytologic analyses. A second 6 week course was given only to patients with incomplete response (positive urinary cytology or recurrent tumor). Three patients received maintenance intravesical BCG. If there was no response at the first cystoscopy after the induction course, no further BCG was given. Side effects were mostly local, moderate and transient, subsiding spontaneously or responding to symptomatic treatment. Severe systemic side effects occurred in three patients. Two with arthritis/arthralgia were managed as out-patients, while one with BCG pneumonitis/hepatitis required hospitalization, triple antituberculosis medication, cloxacillin and prednisolone. Complete response, defined as negative cystoscopy, cytology and histology, was obtained in 11 of 21 cases of papillary carcinoma without concomitant CIS. These patients were followed up for 8-47 months. Of the ten non responders, two died and eight underwent further TUR. Of the 11 patients with concomitant CIS, six showed complete and five no response. Two of the latter died and three had further TUR. In all three cases of primary CIS there was complete response. PMID- 1871560 TI - A classification of urinary calculi with respect to their composition and micromorphology. AB - Texture and micro-morphology of 1615 urinary calculi has been studied using scanning electron microscopy and X-ray micro analysis. Together with the results of X-ray diffractometry concerning their phase composition, a classification into five stone classes, 13 stone groups and 17 sub-groups could be evaluated. Especially the large and inhomogeneous class of the calcium-stones could be resolved into 13 stone types. Using this classification, the stone type is characterized by a three digit number containing the stone class, the stone group and in some cases the sub-group. Criteria for classification are typical texture patterns, the occurrence of special crystalline phases or both. These items are presented and clinical relationships discussed. PMID- 1871561 TI - Nd: YAG contact laser in partial nephrectomy. An experimental study in piglets. AB - The Nd: YAG contact laser technique with 12 W power output was used in partial nephrectomies in six piglets. Blood loss, total time and number of ligatures needed for haemostasis were compared in six partial nephrectomies performed with a steel scalpel. Mean blood loss was 53 g with the laser and 108 g with the steel scalpel (p less than 0.04). The mean time needed for haemostasis were 9.5 and 16.2 min respectively (p = 0.2) and the average number of ligatures required 1.5 and 8.8, respectively. The mean temperature rise at 5, 10 and 20 mm distance from the resection line was 5.3, 1.2 and 0.3 degrees C, respectively. The use of laser reduced blood loss and shortened the operation time. Further studies are needed concerning renal function after kidney surgery with a laser. PMID- 1871562 TI - Cystitis cystica treated with the neodymium-YAG laser. Case report. AB - We report on two patients with severe urgency and pollakisuria where further investigations revealed cystitis cystica (glandularis). Conservative treatment and TUR of the lesions had no effect on the symptoms. After treatment with Neodymium-YAG laser, however, both have been asymptomatic for more than 18 months and urethrocystoscopic examination demonstrated normalization of the bladder mucosa. PMID- 1871563 TI - Opposite renal pelvic metastasis of renal adenocarcinoma. Case report. AB - We report on a 72-year-old patient who was nephrectomized because of renal adenocarcinoma and who developed five years later a tumour in the contralateral renal pelvis. Histological study of the completely resected tumour revealed a metastase from the renal cell carcinoma. A short review of the literature concerning the rare cases of contralateral renal pelvic or ureteral metastases of renal carcinoma is made. PMID- 1871564 TI - [Aseptic meningitis in pediatrics]. AB - We analyzed the 259 pediatric patients (69% males, 31% females) treated for aseptic meningitis at the Department of Pediatrics (Inselspital), University of Berne, Switzerland, during the 10-year period from 1978 to 1987. 79% were in- and 21% outpatients. The main study purpose was the evaluation of clinical presentation, diagnostic workup, course and prognosis of this disease entity. The clinical characteristics (fever, meningitic signs, headache, nausea and vomiting, and usually normal consciousness) were not discriminative for differential diagnosis. On the other hand, pleocytosis in cerebrospinal fluid averaged 406 x 10(6) cells/l (57% mononuclear cells) at first lumbar puncture, and 6 to 12 hours later showed both slight decrease of total cell count and clear shift to mononuclear cells (71%). The course of the disease was always short and benign. Complications, usually of a neurologic nature, occurred in only 10% and all were mild and reversible. Nevertheless, follow-up interview by phone identified 21% of patients with transient post-meningitic disorders, especially prolonged episodes of stress-induced headache. However, except for one case of chronic hydrocephalus, there were no severe or persistent sequelae. Neither complications nor sequelae correlated with patient age or laboratory findings. Our results confirm that aseptic meningitis in children is relatively benign, and underline the importance of rest and relaxation during convalescence. Rapid, reliable and cheap viral diagnostic tests in the cerebrospinal fluid could simplify the management of the individual patient with regard to repeated lumbar punctures (in 36%), surveillance in the hospital (in 79%), and antibiotic therapy (in 25%). PMID- 1871565 TI - [Hypothyroidism and acanthocytes: diagnostic significance of blood smear]. AB - We report on 3 cases of hypothyroidism in which the diagnoses were suspected after having observed acanthocytes on the blood film. The diagnostic value of this erythrocyte change has been neglected, although the results of studies have shown a test specificity of 87-99%, other diseases related to acanthocytes being very rare. After an analysis of the studies and case reports dealing with acanthocytes we conclude that hypothyroidism must be excluded in all cases where acanthocytes are observed on the blood film. PMID- 1871566 TI - [Attemoted suicide in the Bern region]. AB - In a European multicenter study all the suicide attempts in the city and agglomeration of Berne which came under medical treatment during a 12-month period were surveyed. There were 243 females and 153 males, corresponding to a rate of 177.1 and 128.6 per 100,000 respectively. The investigated region can be regarded as representative of Switzerland. Comparison with other centers shows that the incidence of attempted suicide in Switzerland--unlike that of suicide- is approximately in line with the European average. The usual method is overdose of drugs, in particular benzodiazepines. Nearly all the drugs involved in the overdoses were obviously prescribed by physicians. The choice of drugs suggests that many suicidal people deliberately take anxiety-and tension-reducing agents, a fact which points to a relationship between anxiety states and attempted suicide. Both are to be regarded as the expression of acute emotional stress and require an appropriate therapeutic approach. PMID- 1871567 TI - [Spontaneous remission in histiocytosis X with lung and bone involvement]. AB - Histiocytosis X is very rare in the adult. Since the illness is frequently asymptomatic it often causes diagnostic and therapeutic problems. Up to the present, assessment of the long-term course in the adult has required individual case records. A uniform therapeutic concept does not exist. According to prevailing opinion, asymptomatic patients do not require therapy. Our case record describes the spontaneous course in a young asymptomatic patient in whom histiocytosis X, which had affected lungs and bones, healed within 16 months. PMID- 1871568 TI - [Agronomy and veterinary medicine in the tension-filled sphere of development and transformation in Swiss agriculture]. PMID- 1871569 TI - [The effect of the selenium status of goats on the resistance of erythrocytes to oxidative damage]. AB - The effect of selenium status on the development of Heinz body anaemia was studied in 16 three months old Saanen goats which received a diet with a low selenium content. The control group (Se-, n = 8) received no supplementary selenium while the treated group (Se+, n = 8) received selenium by injection. Erythrocyte glutathione peroxidase concentration was significantly higher in the Se+ group than in the control group (105 vs 36 U/g Hgb). The animals were drenched once per day with 30 mg of dimethyl disulphide (DMDS) per kg of body weight for 14 days and with 50 mg per kg during the following 11 days. Erythrocytes with Heinz bodies appeared within one week after increasing the DMDS dose to 50 mg/kg/day and reached a peak one week later (30% and 37% of erythrocytes with Heinz bodies in group Se+ and Se- respectively). Within the next three weeks haemoglobin levels dropped from 135 g/l to 123 g/l and 114 g/l in the Se+ and the Se- group respectively. Differences between the two groups were statistically significant for the percentage of erythrocytes with Heinz bodies and for haemoglobin values (p less than 0.05). The data support the hypothesis that selenium status influences the resistance of ruminants to brassica-induced Heinz body anaemia. PMID- 1871570 TI - [Feed additives in whole milk fattening. Effect on production and health of fattening calves]. AB - In two fattening trials, each time 64 male calves of Simmental x Red Holstein cross breeds were used to investigate the influence of different commercial feed additives containing at the same time antimicrobial agents, minerals and vitamins on growth performance, feed intake, feed conversion and health condition. Calves whose milk diets were supplemented had, depending on products used, higher growth rates (9 to 28%) and better feed conversion rates (2 to 12%) compared to control calves which were fed only whole milk. This improved performance is primarily due to higher feed intakes. It is questionable how much the minerals and vitamins in addition to antimicrobial agents contributed to the improvement. The additional mineral supply caused after 8 weeks a statistically significant higher haemoglobin content, serum magnesium and glutathione peroxidase activity in erythrocytes compared to the exclusive whole milk feeding. Calves which were fed no additives refused feed intake more often as a result of disease incidence and required veterinary treatment more frequently. PMID- 1871571 TI - [Duplex ultrasound of the vertebral arteries. 1. Practical implementation, possibilities and limitations of the method]. AB - Relatively few studies appeared concerning the examination of vertebral arteries because of their difficult visualization based on their anatomical position and on technical problems. The purpose of this report is to describe a technique for the imaging of vertebral arteries at their origins and along their extracranial course. The results of the examination of 54 patients are shown. By measuring the average diameter of the vessel, hypo- or hyperplasia of the vertebral artery can be defined. The problems of visualization of the vertebral origin as well as technical difficulties are discussed. PMID- 1871572 TI - [Duplex sonography of the vertebral arteries. 2. Clinical application]. AB - The purpose of this report is to demonstrate pathological findings such as hypoplasia, stenosis and occlusion that were diagnosed by duplex-ultrasonography of vertebral arteries. Duplex scanning provides complementary to the continuous wave Doppler examination more accurate haemodynamical and morphological information for the diagnosis of hypoplasia or intracranial stenosis. In comparison with DSA this method may give additional information allowing to differentiate between vertebral aplasia and occlusion at the origin. PMID- 1871573 TI - [Vascular space-occupying lesions of the carotid artery--detection with color coded Doppler sonography. Comparison with duplex sonography and angiography]. AB - Nine patients with a cervical tumour, diagnosed by duplex Doppler sonography were additionally evaluated by colour-coded Doppler sonography (CCDS). The duplex Doppler diagnosis of three internal carotid artery aneurysm was confirmed by CCDS in only one patient. In the remaining two cases CCDS identified a marked coiling of the internal carotid artery. Three low echogenic lesions, interpreted as cervical lymphomas by conventional Doppler sonography were identified as two internal carotid aneurysm with partial thrombosis and a carotid body tumour in the third patient by CCDS. Duplex-Doppler sonography and CCDS agreed in the diagnosis of two AV-malformations and one carotid body tumour. Angiography confirmed the CCDS-diagnosis in 7 patients. In the two patients with coiling of the ICA angiographic evaluation was not performed. Thus, CCDS was superior to duplex Doppler sonography in the evaluation of vascular lesions of the extracranial section of the carotid artery and provided additional diagnostic information. PMID- 1871574 TI - [Transcranial color-coded real-time sonography in the adult. 1: Normal findings and cerebrovascular ischemia]. AB - Transcranial colour-coded real time sonography (TCCS) is a new, non-invasive diagnostic bedside procedure allowing two-dimensional imaging of cerebral parenchymatous structures and large intracranial arteries through the intact skull. So far we examined a population of 183 patients und 53 normal subjects, all above 18 years of age. 24 (10%) subjects were not suitable for examination. Two-dimensional imaging of telencephalic, diencephalic, mesencephalic and pontine structures is feasible. Intravascular blood flow phenomena may be analysed quantitatively by an integrated pulsed wave Doppler system. The diagnosis of arterial stenosis and occlusion could be established in 14 patients each by analysing the colour-coded B-mode image and Doppler frequency spectrum. TCCS may complement diagnostic tools in neurology and may improve standardisation of transcranial Doppler measurements. PMID- 1871575 TI - [Microsurgical removal of deep vascular malformations using sonar-stereometry]. AB - The advantages of a new, dynamic sonar technology in open stereotactic microsurgery are demonstrated by means of three surgical procedures for deep seated vascular malformations that are not easy of access. With this method, targets can be aimed at without using rigid, obstructive pointing devices as in conventional stereotaxy. On the contrary, it is possible to take advantage of preformed anatomical spaces reaching the lesion most carefully by means of light weight, free-hand on-target instruments. The spatial information, correlated with a CT data set, is displayed in real time with an accuracy of +/- 1 mm. Additional image data from MR and digital angiography can be used interactively. PMID- 1871576 TI - [Cystic adventitia degeneration of the popliteal artery: sonographic confirmation of the diagnosis]. AB - Cystic adventitial disease is a rare condition resulting in arterial occlusive symptoms. The characteristic clinical and angiographic findings suggest the diagnosis cystic adventitial disease. The presented case shows, that sonography can demonstrate the adventitial cyst and the resulting stenosis and confirm the diagnosis. PMID- 1871577 TI - [Blunt abdominal trauma: differential diagnosis of splenic lobulation and splenic rupture]. AB - In a retrospective study, we analyzed the data of 232 patients with blunt abdominal trauma between January 1, 1984, and December 31, 1988. In emergency ultrasound, we detected 4 patients with a smooth disruption of the splenic outline combined with free peritoneal fluid around the spleen. Because of the blunt abdominal trauma, a rupture of the spleen had to be excluded. In two of these 4 cases, we decided for laparotomy. Intraoperatively, we found a splenic lobulation and no splenic injury in both cases. We conclude that an emergency sonographic examination of the spleen, it should be kept in mind that the anatomical variation of a splenic lobulation might mimic a rupture of the spleen. PMID- 1871578 TI - Mobile tomographic (SPECT) thallium heart studies. PMID- 1871579 TI - GYN cytology--is the glass full or half empty? PMID- 1871580 TI - Memories of a small town: medicine the old fashioned way: Theodore Kammerling. PMID- 1871581 TI - Hyperlipoproteinemias: Part III. When to treat. AB - The recommended treatment goals for patients with hypercholesterolemia who do not have coronary heart disease or two additional risk factors, are a total cholesterol of less than 240 mg/dL and an LDL-cholesterol of less than 160 mg/dL. For patients with coronary heart or two additional risk factors, the goals are 200 mg/dL and 130 mg/dL respectively. The step-one diet is the initial therapy for hypercholesterolemia, followed by the more rigid step-two diet if response has been inadequate. Drug treatment is indicated upon failure of adequate response to six months of dietary therapy, and an LDL-cholesterol of greater than or equal to 190 mg/dL in the patient without coronary heart disease or two additional risk factors, or greater than or equal to 160 mg/dL in the patient with coronary heart disease or two additional risk factors. The decision regarding when to treat patients with hypertriglyceridemia is controversial. Patients with levels greater than 500 mg/dL should at least be treated by diet. A consensus report on the management of children with hyperlipidemia is awaited. The approach to the elderly patient is debated. PMID- 1871582 TI - Hyperlipoproteinemias: part IV. Drug regimens. AB - The bile acid sequestrants and nicotinic acid are the agents of first choice for the treatment of hypercholesterolemia. Experts disagree as to the drug of choice for hypertriglyceridemia, although both nicotinic acid and gemfibrozil are effective. For combined hyperlipoproteinemia, single drug choices include nicotinic acid, lovastatin, and gemifibrozil. Patients with hypercholesterolemia not responding to single drug therapy in conjunction with diet can be treated with a number of drug combinations. PMID- 1871583 TI - Confusion and misunderstanding of some of the terms and practices readily employ in medicine. PMID- 1871584 TI - Medicare physician payment policies: a cost accounting analysis of three internal medicine office practices in South Dakota. AB - Medicare financed visits comprise a higher percentage of these solo internal medicine practices than in solo practices of all types in South Dakota or practices of any type in the USA. Investment opportunity costs, not apparently considered in payment reform policies, in the three practices evaluated are greater than professional liability costs which are highlighted in reform systems. Medicare office visit reimbursement under the Customary, Prevailing and Reasonable (CPR) system did not cover economic costs in these three office practices. The 1991 transition year projections predict practice 1 will lose over $7,000. In the unlikely event that budget neutral provisions are implemented in 1992, the three practices could experience an office revenue increase of 49%, still not equal to the economic incentives of non-Medicare visits. However, the direction taken by the Health Care Financing Administration (HCFA) in developing a model Medicare Fee Schedule would permit an average increase of only 19% to the office charges of the three practices. Office practices 1 and 3 will not break even without increasing Medicare office visit volume by 37% and 57% respectively. PMID- 1871585 TI - Standard Reference Materials for dioxins and other environmental pollutants. AB - The National Institute of Standards and Technology issues approximately 1100 Standard Reference Materials (SRMs) certified for chemical composition or physical properties. A number of these SRMs has been developed to assist chemists in analyzing environmental samples more reliably for chlorinated dioxins and other organic pollutants. Certification of the pollutant concentration in a natural matrix SRM is based on concordant analyses by the NIST Organic Analytical Research Division using at least two independent methods. For a calibration solution, such as SRM 1614, Dioxin (2,3,7,8-TCDD) in Isooctane, certification is based on agreement of the calculated concentration based on the gravimetric preparation and the concentration as determined experimentally. SRM 1614 also includes a 13C-labeled 2,3,7,8-TCDD for use as an internal standard in methods based on gas chromatography/mass spectrometry. The certified concentrations (ng g 1) are 98.3 +/- 3.3 for the unlabeled dioxin and 95.6 +/- 1.5 for the labeled dioxin. The certificates for SRM 1588, Organics in Cod Liver Oil, and SRM 1589, Polychlorinated Biphenyls (as Aroclor 1260) in Human Serum, provide noncertified concentrations of dioxins. Concentrations of chlorinated dioxins in two urban particulate SRMs have been reported in the literature. PMID- 1871586 TI - Human health effects: what the data indicate. AB - Information about the possible human health effects of dioxin is available from studies of chemical plant workers, sprayers of dioxin-contaminated herbicides, and other exposed people. No human illness, other than the skin disease chloracne, which has occurred only in highly exposed people, has been convincingly associated with dioxin. Some epidemiologic studies have suggested associations between dioxin and stomach cancer, soft tissue sarcomas, and lymphomas, but other studies, powerful enough to detect excesses of those diseases, if they exist, have not done so. With the exception of one study of chemical plant workers that reported an excess of stomach cancer, all the suggested associations of increased cancer risks and dioxin exposures are from studies of herbicide applicators. Both direct measurements of the concentrations of dioxin in the body fat of chemical plant workers and the occurrence of chloracne in those men support the conclusion that they were exposed to far greater amounts of dioxin than herbicide applicators. Therefore, if the cancers found in herbicide users were associated with dioxin, even more of those cancers would be expected among the chemical plant workers; the expected increases are not found. In short, epidemiologic studies in which dioxin exposures are known to have been high, either because of the appearance of chloracne or from measurements of dioxin in exposed people, have failed to reveal any consistent excess of cancer. In those studies that have reported associations between exposure and disease, no chloracne was reported, and there are no measurements of higher-than-background levels of dioxin in the people who are classified as exposed. PMID- 1871587 TI - Natural carcinogens and dioxin. AB - Toxicology studies of synthetic chemicals at high doses must be viewed in the context of the world of natural chemicals, which make up the vast bulk of the chemicals to which humans are exposed. In tests at near toxic doses (e.g., the maximum tolerated dose), one-half of all chemicals, whether synthetic or natural, are carcinogens; one-third are teratogens, and about half are clastogens. Natural and synthetic chemicals are similar in their toxicology, and at the low doses of most human exposures where cell-killing does not occur, the hazards may be much lower than are commonly assumed and often will be zero. It is shown that the comparative hazards of dioxin at the levels that are causing concern appear insignificant. PMID- 1871588 TI - Atmospheric lifetimes of dibenzo-p-dioxins and dibenzofurans. AB - The experimental and theoretical data available concerning the gas- and particle phase reactions of polychlorodibenzo-p-dioxins (PCDDs) and polychlorodibenzofurans (PCDFs) are discussed. These data lead to the expectation that the dominant tropospheric loss processes of gas-phase PCDDs and PCDFs will be photolysis and reaction with the OH radical, with the OH radical reaction being the most important for the less chlorinated species. The estimated tropospheric lifetimes of gas-phase PCDFs increase significantly more rapidly with the degree of chlorination than is the case for PCDDs. For particle associated PCDDs and PCDFs, the dominant tropospheric removal processes are expected to be photolysis and wet and dry deposition, with wet and dry deposition of the host particles being the most important. The estimated lifetimes in the lower troposphere range from less than 1 day for dibenzo-p-dioxin, the mono-, di- and trichlorodibenzo-p-dioxins, dibenzofuran and the monochlorodibenzofurans present in the gas phase, to greater than or equal to 10 days for particle associated PCDDs and PCDFs, with a general increase in the tropospheric lifetime with the degree of chlorination. While long-range transport of PCDDs is expected to occur for those PCDDs which are totally or mainly particle associated, gas- and particle-phase PCDFs containing four or more chlorine atoms are also expected to have sufficiently long tropospheric lifetimes to undergo long-range transport. PMID- 1871589 TI - A model for de novo synthesis and decomposition rates of dioxins and furans in municipal waste incinerators. AB - We present a concise summary of a de novo synthesis model for the rates of formation of dioxins and furans in incinerators. Representative numerical results are used to illustrate numerical predictions and their utilization. PMID- 1871590 TI - Some laboratory experimental designs for obtaining dynamic property data on dioxins. AB - The presence of polychlorinated p-dibenzodioxins and polychlorinated dibenzofurans (hereafter PCDD/F) in municipal waste incinerator effluents has sparked a variety of laboratory investigations in the last few years in the hope of learning more about the formation and destruction mechanisms of these compounds. In the course of the investigations a variety of approaches have been employed. It is the purpose of this paper to review these designs and to comment on them in general as well as in specifics. Since under the conditions of interest the quantities of PCDD/Fs are miniscule compared with other products and reactants and because there are nearly 200 congeners, quantitative information is difficult and expensive to obtain. A second aspect concerns the reaction rates involved. No intrinsic kinetic studies have been conducted and no intrinsic values for PCDD/F rates of formation exist. Such information will be necessary, however. As will be shown below, there seems to exist a basic conflict between reaction rates as may be inferred from some laboratory experiments and rates seemingly required by the time/temperature histories of gases and particles in incinerators. The paper is divided into four major parts: homogeneous formation and destruction, heterogeneous formation and destruction, comments on discrepancies, and suggested designs. PMID- 1871591 TI - Toxicity equivalents and EPA's risk assessment of 2,3,7,8-TCDD. AB - Toxicity equivalent factors (TEFs) have proved useful in estimating the toxicity of complex mixtures of chlorinated dibenzo-p-dioxins and dibenzofurans (CDDs/CDFs). An international consensus has formed around a specific set of TEF values as interim solution for addressing environmental contamination by CDDs/CDFs. This procedure capitalizes on the congener-specific analytical results that are more routinely available in recent years. The TEF approach should be updated as necessary and replaced by more definitive bioassay approaches as soon as practicable. In an independent activity, the USEPA considered a proposal to change (reduce) the cancer potency ascribed to 2,3,7,8-TCDD by a factor of 16. The recommendation was based upon an analysis of the literature and the Agency's earlier risk assessment. The proposal was reviewed by the Science Advisory Board, a group of outside scientific advisors. Subsequently, the Agency decided against making any changes in its assessment at this time. However, it is likely that a reassessment will be conducted shortly that will incorporate new data and a new approach to estimating of cancer risks posed by 2,3,7,8-TCDD. PMID- 1871592 TI - Air emissions from municipal waste combustion and their environmental effects. AB - This paper addresses risk-assessment estimates associated with air emissions from MWC facilities via the inhalation pathway. Calculations performed address selected chemical constituents with the potential highest human health effects. The calculated carcinogenic risks are small and are well below the EPA acceptable risk of 10(-4). Similarly, the calculated noncarcinogenic risks are well below the acceptable reference dose values. Calculations presented in this paper for selected constituents could be expanded to additional chemical constituents. PMID- 1871593 TI - Human exposure to dioxin. AB - Because 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent chemical carcinogen evaluated by the U.S. Environmental Protection Agency (EPA), many people fear that exposure to even small amounts of TCDD could lead to serious health effects. Ambient measurements confirm that environmental TCDD contamination is widespread. The public is concerned about TCDD exposure from such diverse sources as municipal solid waste incinerators, pulp and paper mills, and contaminated fish and soil. This paper evaluates several critical issues including: (i) the extent of background contamination; (ii) accumulation in the food chain and the potential for human exposure from ingesting contaminated food items; (iii) the magnitude of TCDD emissions into the U.S. environment, and the relative contribution of various known TCDD sources to the total TCDD load; and (iv) setting environmental standards for TCDD. PMID- 1871594 TI - NIH bill to mandate ROTC program for biomedicine and data sharing. PMID- 1871595 TI - Tape trouble. PMID- 1871597 TI - Healy returns fire at Dingell hearing. PMID- 1871596 TI - Testing for cancer risk: tough questions ahead. PMID- 1871598 TI - Brain cancer near Los Alamos? PMID- 1871599 TI - Changes ahead for gene therapy review process? PMID- 1871600 TI - A novel, highly stable fold of the immunoglobulin binding domain of streptococcal protein G. AB - The high-resolution three-dimensional structure of a single immunoglobulin binding domain (B1, which comprises 56 residues including the NH2-terminal Met) of protein G from group G Streptococcus has been determined in solution by nuclear magnetic resonance spectroscopy on the basis of 1058 experimental restraints. The average atomic root-mean-square distribution about the mean coordinate positions is 0.27 angstrom (A) for the backbone atoms, 0.65 A for all atoms, and 0.39 A for atoms excluding disordered surface side chains. The structure has no disulfide bridges and is composed of a four-stranded beta sheet, on top of which lies a long helix. The central two strands (beta 1 and beta 4), comprising the NH2- and COOH-termini, are parallel, and the outer two strands (beta 2 and beta 3) are connected by the helix in a +3x crossover. This novel topology (-1, +3x, -1), coupled with an extensive hydrogen-bonding network and a tightly packed and buried hydrophobic core, is probably responsible for the extreme thermal stability of this small domain (reversible melting at 87 degrees C). PMID- 1871601 TI - Genes for epilepsy mapped in the mouse. AB - The neurological mutant mouse strain E1 is a model for complex partial seizures in humans. The inheritance of epileptic seizures with seven conventional chromosomal markers and over 60 endogenous proviral markers was studied by means of back-crosses of E1 with two seizure-resistant strains, DBA/2J and ABP/LeJ. The major gene responsible for this epileptic phenotype (El-1) was localized to a region distal with respect to the centromere on chromosome 9. At least one other gene, El-2, linked to proviral markers on chromosome 2, also influences the seizure phenotype. In addition, a potential modifier of seizures was detected in the DBA/2J background. The location of El-1 on distal chromosome 9 may allow identification of an epilepsy candidate gene in humans on the basis of conserved synteny with human chromosome 3. PMID- 1871602 TI - Alteration of the phase and period of a circadian oscillator by a reversible transcription inhibitor. AB - A function for transcription in the mechanism of a circadian oscillator was investigated with the reversible transcription inhibitor 5,6-dichloro-1-beta-D- ribobenzimidazole (DRB). Two-hour treatments with DRB shifted the phase of the circadian rhythm of the isolated eye of Aplysia, and continuous treatments of DRB lengthened the free running period of this rhythm. Camptothecin, an inhibitor of transcription that is structurally unrelated to DRB, had similar effects on the circadian rhythm. These results suggest that transcription may be part of the circadian oscillating mechanism. PMID- 1871603 TI - Counting and discounting the universe of exons. PMID- 1871604 TI - The quality of life of cancer patients who refuse chemotherapy. AB - The study compared the quality of life of 51 cancer patients who dropped out of chemotherapy, 19 who refused treatment and a further 70 patients who had completed chemotherapy. The patients were treated in five oncological institutes in Israel. The findings of this study indicate that the quality of life of patients who refuse chemotherapy is no different from that of patients who drop out of treatment or patients who complete treatment. The findings also show that the quality of life of the patients who drop out of treatment is worse than that of patients who complete chemotherapy. PMID- 1871605 TI - Culture, biomedicine and child mortality in Cameroon. AB - This article is based on a field study conducted by the authors in East Cameroon in 1987-1988 and on written sources available, including U.N. and Cameroon government statistics. It focuses on two major issues, namely, the relationship between biomedical assumptions and programs and traditional cultural tenets and the impact of both on child mortality in Cameroon's East Province. It contrasts the problems of disease and mortality in the area as reflected in official statistics with the actual health situation in the Province in light of resilient beliefs, attitudes, and practices that hinder rather than facilitate the effectiveness of immunization campaigns undertaken by the government to save the child. The study concludes by discussing policy choices and steps that both the government and the affected people might consider to remedy the region's disappointing health conditions. PMID- 1871606 TI - Rural health and labour supplies: empirical evidence from the World Bank Assisted Agricultural Development Project in the Kwara State of Nigeria. AB - The efforts made in this study are in two areas. First, an effort has been made to determine whether there are any health or labour supply differences between ADP and non-ADP households. Second, an effort has also been made to determine whether differences in health, housing and nutrition, if any, have an effect on labour supply. All the efforts are attempts to focus research attention on the Nigeria's resource endowment factor and at the same time assess the impact of rural infrastructure capital and thus the World Bank Assisted Agricultural Development Projects (ADP) on the rural Nigerian residents and their industry. Using 175 households, 50 from the ADP and 125 from the non-ADP areas, the discriptive statistic indicates strong mean significant differences for the descriptors of nutrition, housing and state of health among the two sample categories. The discriminant function strongly discriminates between the two sample groups while the multiple regression analysis establishes a causal relationship between the discriptors of rural healthy days and labour supply for the two sample data sets. The policy implication of the study is that the implementation of the ADP particularly the Ilorin, leads to the improvement of quality of life and greater infusion of high quality labour into the rural agricultural industry. Higher productivity and increased farm family income and enhanced rural life which results is a useful virile circle necessary for laying the bedrock for the rural development. PMID- 1871607 TI - Cree Indian healing practices and western health care: a comparative analysis. AB - In this article, Cree Indian methods of treating disease are compared with the treatment process and procedures used in the Western health Care system. Ethnographic data permitted the identification of the five components of Cree healing: the ritual, contract, treatment, didactic, and closure components. These components are compared with equivalent phases in the physician-patient and nurse patient relationship. In particular, the process of comparison permits the identification of incongruities that the Cree may encounter when using the Western system. These include the inability to identify one's own state of health and abnormalities; a passive, rather than a participatory role in healing; the incomprehensible notion of "silent" diseases and preventative treatment; the specialization of the caring, curing, and counselling roles of practitioners and the limited perspective of "holism" in health care. PMID- 1871608 TI - Prostitution, AIDS, and preventive health behavior. AB - Although considerable attention has been placed on the role of prostitutes in the AIDS epidemic, little attention has been directed to features of prostitutes' work lives which are relevant to the control of AIDS. This article reviews several aspects of prostitution in the United States which have implications for control of the epidemic. The article first reviews the epidemiology of human immunodeficiency virus (HIV) infection among prostitutes. The legalized system of prostitution in Nevada serves as a basis for comparison to illegal prostitution. This article examines the effectiveness of mandatory testing of prostitutes for monitoring and controlling the epidemic. And finally, a peer education approach as a means to control HIV infection among prostitutes is explored. PMID- 1871609 TI - Response of parents to five killer diseases among children in a Yoruba community, Nigeria. AB - This paper examines the various ways through which adults' health beliefs and attitudes affect their responses to five major killer diseases during childhood. The data for the study were derived from in-depth interviews conducted between December 1988 and January 1989 in a Yoruba community, Nigeria. The diseases covered in the study include diarrhoea, measles, tetanus, pertussis and fever. It was observed that teething and food related causes were believed to be responsible for diarrhoea; the cause of measles and pertussis was generally unknown; tetanus was usually associated with convulsions; and fever was believed to be caused by roaming in the sun and by constipation. Herbal tea, modern drugs and prayers were the most commonly prescribed treatments for these diseases. It was observed that most mothers used alternative sources of health care, rather than hospitals, clinics and maternity centres, in their treatment of diseases among children. Prominent among the alternative sources were patent medicine stores where there were personalistic social interaction between clients and operators, free consultancy and flexible pricing. Parents' location at the time of a child's sickness, access to good advisers, the perceived seriousness of the sickness and religious beliefs of mothers were important determinants of their response. Avoidance of blame was noted to be a major motivating force in parents' search for potential sources of health care. The paper concludes that although some of the practices might have negative health implications, they could be usefully adapted to the goal of self-reliance in medical care as a strategy for attaining health for all by the year 2000. PMID- 1871610 TI - Informed consent: a study of experiences and opinion of utilizers of health services from India. AB - One hundred and forty-eight subjects drawn from urban and rural settings who had been hospitalized for any medical problem within the previous three years were interviewed using a semi structured interview schedule to understand their opinion and experiences of informed consent. Sixty medical officers providing primary care in both urban and rural areas were concurrently interviewed to gather their opinion. Results revealed that respondents were dissatisfied with the information they had received about the different aspects of their illness. Both the doctors and the patients felt the need for providing adequate information to utilizers of health services. The two groups identified certain constraints, like illiteracy, in obtaining informed consent. Doctors compared to patients more often thought that illiterates could not understand the information. Patients more often felt that information about nature of investigations and about prognosis need not be routinely revealed. PMID- 1871611 TI - Diffusion and physiological responses to the influenza pandemic of 1918-19 in Nigeria. AB - Although virologists are not in agreement on the origins of the 1918-19 influenza pandemic, it has long been associated with the virulent type A virus. At least 21 million people died from the disease over a 12-month period, becoming one of the world's worst short-term demographic disasters. The disease was introduced into Nigeria by passengers and crews who arrived via ship from overseas. Thus, coastal ports were the primary focus of the diffusion of the disease. Its spread to the hinterland was facilitated by improvements in transportation technology. Neither maritime quarantine, nor the isolation of patients checked the spread of the disease. About 500,000 Nigerians, out of a population of 18 million, died in less than 6 months, and between 50 and 80% of the population was stricken. The over crowded urban centers were the hardest hit and, even though pandemic declined almost as suddenly as it began, morbidity, mortality, and panic adversely affected the productive capacity of the country. Since the 1930s, virologists have gained much knowledge about the agents responsible for influenza diffusion, but the disease remains one of the few plagues to be eradicated. This is partly because of the exceptional adaptability of influenza viruses, and partly because artificially and naturally-acquired immunity to influenza are temporary in duration, making reinfection possible even by the same type or subtype of influenza. PMID- 1871612 TI - Why are we weighting? A critical examination of the use of item weights in a health status measure. AB - There is currently much interest in the measurement of self reported health status. A number of health status measures have been designed. However, such questionnaires are often long and complicated, or are disease specific. The most famous generic British health status instrument is the Nottingham Health Profile (NHP) which is a short questionnaire designed for ease of completion. However, this paper addresses a number of related issues concerning the weights attached to particular items on this questionnaire. It is argued that the weighting of items by Thurstone's method of paired comparisons is inappropriate and can lead to logically inconsistent results. PMID- 1871613 TI - Maternal role of clerical workers: a feminist analysis. AB - This paper presents the qualitative findings about women's maternal role from an interview study of role integration and health in a U.S. sample of 87 women clerical workers. The data draws from clerical women's perceptions of the satisfactions and stresses they experience in their roles as mothers, the coping strategies they use, and the resources available to them. The analysis provided is based on participants' descriptions of their subjective experiences as mothers within the larger context of managing domestic responsibilities and fulltime jobs outside their homes. Results suggest that women in clerical jobs find many aspects of their maternal role satisfying, like participating in their children's growth, nurturing them, receiving unconditional love, and finding companionship. However, they identify multiple and pervasive stresses including boundless worries, strained relationships, overload, child care problems, and financial burdens. Many of their coping strategies are solitary in nature, although they also engage in active problem-solving, especially when they have to juggle child care and occupational responsibilities. Many do not view their spouses as sources of emotional and tangible support in childrearing. In addition to an in-depth discussion of qualitative findings, the authors examine implications for social policy, intervention, and future research about multiple roles and health. PMID- 1871614 TI - [Organ-sparing gastrectomy in peptic ulcer]. AB - Experimental and clinical data show the zone of hormonal stimulation of gastric juice secretion and that of parietal gastric hydrolysis to have well-defined borders coinciding with anatomical reference points, to be characterized by multidirectional gradient and to be a local mechanism regulating secretory and motor gastric activity. The condition of the lesser curvature ++muco-epithelial complex is one of the factors operable in development of gastroduodenal ulcer. It is hold that resection of hormone--contact zone of the stomach is a preserving, effective and available means of surgical management of gastroduodenal ulcer. PMID- 1871615 TI - [Study of the status of energy metabolism in thyrotoxicosis by the insulin test]. AB - The insulin test was carried out in 68 healthy subjects and 20 patients with moderate thyrotoxicosis at the stage of compensation. Blood levels of pyruvate and lactate, plasma and erythrocytic glucose, urinary catecholamines and gas exchange were measured before, 30 and 120 min after intravenous administration of insulin (0.15 U/kg). All the measurements evidenced hypermetabolism: oxygen consumption, carbonic acid production, pulmonary ventilation were enhanced; lactate-pyruvate index and urine catecholamines were lower versus those of healthy subjects. Correlation analysis demonstrated disturbed regulation of hyperventilation by the sympathetic-adrenal system in thyrotoxicosis. PMID- 1871616 TI - [Brain function before and after sleep deprivation in patients with primary generalized epileptic seizures]. AB - A clinical analysis covers 11 patients with primary-generalized spastic epilepsy aged 15-43 (9 males and 2 females). Sleep deprivation showed EEG-recorded extreme stress of the brain activating structures necessitating corresponding vascular response. Rheography records cerebral hemodynamics and provides control of vascular drugs effect in relevant patients. PMID- 1871617 TI - [Histological and immuno-morphological characteristics of differentiated cancer of the thyroid gland]. AB - Histological and immunomorphological study of the removed tumor and tissue of the thyroid was performed in 80 patients with differentiated thyroid cancer. Activation of immune reactions and immunocompetent cells was reported at the border with blastomatous process. The latter seems a factor contributing to a favorable run of differentiated thyroid cancer. The capacity of papillary and follicular cancer for multifocal growth limits indications for preserving surgery in such lesions. PMID- 1871618 TI - [Clinical aspects, diagnosis and surgical treatment of developmental anomalies of the cervical spine]. AB - The examination of 20 patients with abnormal cervical spine has identified Klippel-Feil disease in 12 of them, isolated vertebral synostoses of the cervical spine in 8. In 2 patients with Klippel-Feil anomaly neurovascular syndrome was reported which resulted from compression of the neurovascular bundle by extra cervical ribs. Indications to surgical treatment in Klippel-Feil disease are specified. The authors performed operations to correct the cosmetic defect and relieve compression of the neurovascular bundle in neurovascular syndrome. PMID- 1871619 TI - [Principles of pathogenetic treatment of spontaneous cyclic abdominal pain in women]. AB - Available are the results of treatment of 104 females suffering from spontaneous cyclic abdominal pain. Clinical and paraclinical evaluation shows that sensibilization to certain estrogen fraction in the presence of estrogen progesterone++ imbalance plays the leading role in pathogenesis of cyclic (phase I, II and in the middle of the cycle) abdominal pain. Desensitization by intracutaneous introduction of relevant estrogen fraction combined with progesterone++ provides recovery of vegetative and estrogen-progesterone++ balance, relief of pain and emotional stress. A complete response was achieved in 64.4%, partial in 25%, no response in 10.6% of the patients. Follow-up lasted for 1 to 17 years. Additional rehabilitation measures are suggested. The diagnosis and treatment were performedon the outpatient basis. PMID- 1871620 TI - [The role of the major histocompatibility complex antigens in the development of allergic diseases in the Korean population]. AB - Association has been detected between incidence of HLA-antigens and allergy prevalence in Koreans. Antigen B8 occurs significantly more frequently whereas A3 more rarely in Koreans with allergy. Determination of HLA-antigens distribution may be helpful in prognosis of allergic diseases possibility. Allergies are a rare finding in Koreans due to less common occurrence of antigens AI and B8 in them against Europeans. PMID- 1871621 TI - [Use of the greater omentum for reconstruction of the chest]. PMID- 1871622 TI - [Neurological aspects of microcrystalline arthropathies]. PMID- 1871623 TI - [Work capacity of surgeons during operations]. PMID- 1871624 TI - [Ways to improve secondary prevention of malignant neoplasms]. PMID- 1871625 TI - [Effect of quantum hemotherapy on blood oxygen transport in the early stages of myocardial infarction]. PMID- 1871626 TI - [Heart rupture and aneurysm]. PMID- 1871627 TI - [Analysis of errors in the management of patients with stenocardia in an urban polyclinic and the ways of their correction]. PMID- 1871628 TI - [Extending the diagnostic possibilities of tetrapolar chest rheography]. PMID- 1871629 TI - [Central, pulmonary and hepatic hemodynamics at the developmental stages of cardiopulmonary insufficiency]. AB - The analysis of correlations between the time and speed parameters found out that in healthy subjects and patients with chronic nonspecific bronchitis (CNB) the blood flow in great hepatic vessels is provided by the amount of blood entering the aorta in the systole. When central hemodynamics is affected in the CNB exacerbation, this factor becomes essential also for the arterial inflow into middle-size and small branches of the hepatic artery. Persistent bronchial obstruction and labile pulmonary hypertension rise as a result of failure of adequate relations between systemic, pulmonary and hepatic hemodynamics. The condition of great arterial vessels of the liver gets dependent on lesser and greater circulation. The response of the middle-size and small branches of the hepatic artery in chronic obstructive bronchitis (functional class II) is independent of the vascular tone of the lesser and greater circulation. The conclusion is made that intrahepatic blood flow in patients with secondary pulmonary hypertension is regulated by vasoactive factors acting at the level of the organ (mainly kallikrein-kinin system and prostaglandins). PMID- 1871630 TI - [Effect of exercise on pulmonary circulation in chronic bronchitis]. PMID- 1871631 TI - [Possibilities of immunotherapy in chronic pancreatitis]. PMID- 1871632 TI - [Status of the pancreas in the group of persons participating in liquidation of the sequelae of the accident at the Chernobyl nuclear power plant]. PMID- 1871633 TI - [Possibilities of phototherapy in the complex treatment of non-healing peptic ulcers]. PMID- 1871634 TI - [State of immunity in wound complications after herniotomy]. PMID- 1871635 TI - [Suppurative meningitis and meningoencephalitis in middle-aged and elderly patients]. PMID- 1871636 TI - [Androgen treatment of sex disorders in men with epilepsy]. PMID- 1871637 TI - [Treatment of prednisolone-dependent form of multiple sclerosis]. PMID- 1871638 TI - [Results of follow-up of patients with diabetes mellitus type 1]. PMID- 1871639 TI - [Plasma triacylglycerols in alimentary obesity]. PMID- 1871640 TI - [Treatment of thyrotoxicosis with anaprilin and mercasolil]. PMID- 1871641 TI - [Diagnosis of staphylococcal infection in measles]. PMID- 1871642 TI - [Biochemical examination of the blood and cerebrospinal fluid in complicated forms of pneumococcal infection]. PMID- 1871643 TI - [Breast cancer in young age]. PMID- 1871644 TI - [The role of pancreatic polypeptide in the pathogenesis of malabsorption in ulcerative colitis]. AB - Pancreatic function was evaluated in 16 22-56-year-olds with ulcerative colitis. The diagnosis was verified by coprogram, glycemic curves, blood and urine amylase, ultrasound and endoscopic findings. A basal level of pancreatic polypeptide (PP) was measured in blood serum under glucose tolerance test (50 g) using radioimmunoassay. Intracavitary pH-metry provided data on pH in the upper gastrointestinal tract. The results were processed according to Student's t criterion. The evidence demonstrated pancreatic involvement with secretory and endocrine insufficiency leading to homeostatic derangement of enteral medium and malabsorption in ulcerative colitis. The addition of pancreatic enzymes and antacids is advisable as pathogenetically valid. PMID- 1871645 TI - [Fractures of the distal segment of the humerus]. PMID- 1871646 TI - [Treatment of ununited fractures and pseudarthroses complicated by suppurative infection]. PMID- 1871647 TI - [Intestinal obstruction caused by cholelithiasis]. PMID- 1871648 TI - [Drug embolization in pancreatic carcinoid tumor with metastases to the liver]. PMID- 1871649 TI - [Pulmonary mask of intestinal carcinoid tumor with hypereosinophilic syndrome]. PMID- 1871650 TI - [Exercise therapy of post-mastectomy edema]. PMID- 1871651 TI - [Comparative effectiveness of various beta adrenergic blockaders in hypertension]. PMID- 1871652 TI - [Elastoviscosimetry in maxillo-facial pathology]. AB - In the oro-maxillo-facial pathology it may be useful to perform hematochimical and saliva tests which can clarify the kind of the pathology and which can be used in the post-surgical follow-up because of incidental modifications. Saliva compliance and viscosity and blood hemorrheology variations always result lower than in normal population. The Authors are going to value which kind of oro maxillo-facial pathologies shows a significant reduction of saliva elastoviscosity and blood hemorrheology. Yet, in a further study, they will try to explain that reduction and the connection with the specific pathology and the medical and/or surgical treatment. PMID- 1871653 TI - [Innervation of inflammatory periapical lesions. Histopathological aspects]. AB - The authors through a literatures, review, shows the istopathological aspects of the innervation of the inflammatory periapical lesions, emphasizing the most important characteristic. PMID- 1871654 TI - [Symptomatic and surgical results after integrated CT-MR study of a central giant cell tumor of the maxilla]. AB - The AA. examine the possibilities of the present imaging to the diagnostic definition of the extensive and destructive forms of the Central Giant cells Tumor of the maxilla. The CT and MR studies are compared with conventional x-Ray. The analysis performed evinces, besides the well-known semeiological CT superiority for the evidence of the osseous erosions, the ability to follow by MR imaging the evolution of the tumor, in the its relationships with the fascial, muscular, adipose and fibromucous soft tissues, when it exceeds the osseous barrier of the maxillofacial skeleton, enclosed therein the palatal plane. PMID- 1871655 TI - [Histo-ontogenetic study of the major salivary glands and Chievitz's organ]. AB - Salivary glands development has been studied by optical microscopy in 8 fetuses aged from 8 to 20 weeks of fetal life. From the observation of the sections obtained we can assume that submandibular gland is the first gland to be detectable, later the parotid gland and then the sublingual gland. In tight connection with the parotid gland Chievitz organ has been demonstrated. It is not known whether this organ may or may not contribute to parotid gland. PMID- 1871656 TI - [Modern views on treating tooth discoloration from tetracycline]. AB - The Authors, having widely examined literature about genesis and methods of treatment of the tetracycline-induced discoloration of the teeth, had clinically studied a new way of bleaching discolored teeth called B.V. Bleaching Vital, they also described the execution's technique of this method. PMID- 1871657 TI - [Fluoride levels in mother's milk]. AB - Using an electrode selective for the ion fluorine, it has been determined the amount of fluorine in samples of human milk. In a sample of 35 nursing mothers, only 10 have shown the required parameters. The amount of fluorine in the water all 35 mothers imbibed in their daily diet has been measured. The results showed a small amount of fluorine in human milk and a possible connection between the amount of fluorine in the mothers' daily diet and the amount of fluorine in human milk. From the results of the research it has been determined the necessity to give supplements of fluoride to nursing babies. PMID- 1871658 TI - [Comparison of telethermography and electromyography in instrumental symptomologic evaluation of the anterior temporalis and the masseter]. AB - In 10 young subjects without pain or tenderness over the masseter and anterior temporal muscles left and right, skin surface temperature was measured over the area of these muscles, these subjects then underwent to an electromyographic examination for masseters and temporals. The findings obtained by these two different diagnostic tools were compared. From these comparison it comes out that in a large percentage of our sample they showed the same diagnostic result. PMID- 1871659 TI - [Motivation for seeking periodontal care in a Palermo population]. AB - The Authors find a disagreement between symptomatology referred by patients and clinical pictures of pathology observed by sanitary operators. For instance a large percentage of patients considers bleending less important than the presence of calcolus. It is necessary a better information and secondary prevention increased. PMID- 1871660 TI - [Hypnosis for sedation and ambulatory analgesia in dentistry]. AB - The hypnosis present various applications in the therapy of different oral pathologies. The hypnosis is helpful whether how assistance to the local anesthesia in anxious patients, or in the patients with cardiovascular disease, or in the patients with allergic symptom to anaesthetic drugs or in other various conditions. The present work shows the factors that are important for a adequate hypnotic methodology combined with local anesthesia in oral pathology; for this we have execute a clinical work with forty patients treating with various therapeutic treatment. PMID- 1871661 TI - [Some histological preparation methods of dental significance]. AB - The authors inspect some of the most usual methods used in the preparation of histological sections of odontological interest. Then they describe a recent method of preparation of histological sections invented by the Prof. K. Donath. It makes use of modern instruments and allows the preservation, in the specimen, of tissues of different nature and consistence, and of eventual materials of restoration and of implant, present in the teeth or in the bone. PMID- 1871662 TI - [Cinematography of the wrist]. PMID- 1871663 TI - [Fibrosarcoma of the cervical spine. Differential diagnosis and treatment]. PMID- 1871664 TI - [Bone manifestations of a systemic amyloidosis]. PMID- 1871665 TI - [MR tomography of spondylodiscitis]. PMID- 1871666 TI - [The suitability of the surface-dose product for the evaluation of different film screen systems in relation to their sensitivity in practice]. PMID- 1871667 TI - General practice residency education in implant dentistry. PMID- 1871668 TI - Endoscopic treatment of gastric cancer. AB - We analyzed 445 cases of early gastric cancer to confirm which were associated with lymph-node metastases. Overall, gastric cancers less than 2 cm in size, without an ulcer or ulcer scar, or protuberant or mixed morphology could be expected to be free of lymph-node metastases. In these patients with early gastric cancer without lymph-node metastasis, local treatment using surgical endoscopy could effectively eradicate the disease. Laser irradiation was performed in 44 cases and mucosal resection in 18 cases. All early gastric cancers less than 2 cm in size, with the exception of those located in the prepylorus or high on the posterior wall of the body of the stomach were eradicated by laser irradiation. Mucosal resection was used to ablate cancers less than 1 cm in size and with the exception of 1 case, total clearance was obtained. We conclude that early gastric cancer without lymph-node metastases can be eradicated by surgical endoscopic treatment. PMID- 1871669 TI - The use of endoscopic ultrasound in determining the depth of cancer invasion in patients with gastric cancer. AB - Endoscopic ultrasonography (EUS) was performed in 110 patients with gastric cancer to examine the depth of cancer invasion. The normal gastric wall has a five-layer structure on EUS. In 19 lesions, changes on EUS were limited to the first and/or second layers, suggesting that invasion was limited within the mucosa. In 91 lesions, changes were evident in the third or deeper layers. Alterations in the EUS appearance could be divided into two types: type A, with destruction of the layered structure and type B with thickening of the layers. The amount of interstitial tissue in cancer was classified as medullary or intermediate in 90% of type A, and as scirrhous in 82% of type B tumor. The EUS diagnosis of invasion was 95% accurate for stage M cancers, 75% for SM, 64% for PM, 100% for SS, 79% for SE, and 100% for SI lesions. The overall accuracy was 81%. Accompanying fibrosis and metastatic perigastric nodes were the main reasons for overestimating the extent of disease. PMID- 1871670 TI - Endoscopic diagnosis of submucosal gastric lesions. The results after routine endoscopy. AB - The accurate diagnosis of submucosal gastric lesions is difficult. In an attempt to study this problem, the endoscopic records for 8 consecutive years (July 1976 June 1984) were scanned with the help of a computer-based registration of the endoscopic findings. The examinations were identified in which the endoscopic diagnosis indicated the presence of a submucosal tumor. Fifty-four such patients were found in 15,104 routine examinations, giving an incidence of 0.36%. Six patients were lost to follow-up, so the study is based on 48 patients. The most common reason these patients underwent endoscopy was abdominal pain. Five patient groups were identified: (a) nine patients were correctly diagnosed as having gastric wall neoplasia at the initial endoscopy + biopsy; (b) in an additional 13 patients, the suspected gastric wall neoplasia was verified by further nonoperative diagnostic procedures; (c) five patients were found to have benign non-neoplastic gastric disease; (d) five patients had extra-gastric disease that pressed against the gastric wall; (e) in 14 patients a further work-up indicated that the initial endoscopy was false-positive. These five groups were confirmed by additional diagnostic procedures (including laparotomy) and a follow-up time of more than 5 years or autopsy. Two patients refused further examinations and died shortly afterward. No autopsies were performed. Based on our data, it would seem that in the vast majority of patients the suspicion of a submucosal gastric lesion at endoscopy indicates the presence of a serious condition. PMID- 1871671 TI - Endoscopic injection sclerotherapy in non-variceal upper gastrointestinal bleeding. A comparative study of polidocanol and thrombin. AB - To date several agents have been used to achieve haemostasis in patients with non variceal upper gastrointestinal bleeding using endoscopic sclerotherapy techniques. Polidocanol has been widely used but local complications have been reported after treatment. We have compared the efficacy and safety of thrombin and polidocanol in 82 consecutive patients with ongoing or recent bleeding from duodenal, gastric, or anastomotic ulcers. Primary control of haemostasis from spurting vessels was achieved in 90% of cases using polidocanol and in 86.6% using thrombin. Definitive haemostasis was obtained in 80% of patients in both groups. When a non-bleeding vessel was visible, injection of polidocanol or thrombin effectively prevented rebleeding in 90.9% and 85.7% of cases, respectively. When a non-bleeding sentinel clot was present, injection of polidocanol or thrombin provided definitive haemostasis in 100% and 92.8% of cases, respectively. No statistically significant difference was evident between the two agents. In the polidocanol group, one local haemorrhagic complication was noted. No general or local complications were recorded in the thrombin group. PMID- 1871672 TI - Duodenal varicose veins. AB - Duodenal varices (DV) are rare. We present a review of published cases with emphasis on the management and outcome, as illustrated by our own cases, which reflects the experience reported in the literature. The diagnosis of DV must be considered in patients with gastrointestinal bleeding. Two-thirds of all reported cases have portal venous hypertension caused by hepatic cirrhosis. In the remaining one-third prehepatic portal hypertension as a consequence of either a compromised portal venous circulation (caused by perivenous tumor or inflammation) or a primary haematological disease is the underlying cause. Previously, duodenoscopy has often failed to detect and correctly interpret DV, and was similarly unsuccessful in our case. This case report demonstrates the problems and shortcomings in the management of DV and documents a hither to unreported cause. Treatment depends on the severity of bleeding. When conservative measures cannot control the haemorrhage, emergency laparotomy may be indicated. The type of surgery should be chosen according to the aetiology, site and extent of the bleeding DV. Among 112 reported cases of DV, information on outcome exists for only 35 patients who presented with haemorrhage. The aetiology was liver cirrhosis in 26 of these patients, 10 of whom had a fatal outcome, and prehepatic portal hypertension in the remaining 9, 1 of whom had a fatal outcome. PMID- 1871673 TI - Intraoperative ultrasonographic detection of occult liver metastases in colorectal cancer. AB - The efficacy of intraoperative ultrasonographic detection of colorectal cancer liver metastases was evaluated in 85 patients undergoing operation for primary colorectal tumors or liver secondaries. The results of intraoperative ultrasonography were compared with those of preoperative ultrasonography and computed tomography, as well as the intraoperative appearances of the liver. Additional information about the number of metastases was obtained in 12 cases (14.1%); 17 (24.3%) out of 70 metastases could only be detected by intraoperative ultrasonography. In 4 cases (4.7%) these lesions were solitary. As a result, the operative procedure of choice was changed in 15.3% of the patients. We conclude that intraoperative ultrasonography has a significantly higher ability to detect colorectal cancer liver metastases than preoperative methods or intraoperative inspection and palpation. Intraoperative ultrasonography should be performed in patients without preoperative evidence of liver metastases and in all patients with planned resection of metastases. PMID- 1871674 TI - Value of sonography for follow-up examination after allogenic kidney transplantation. AB - In 66 patients with renal transplants 246 sonographic examinations were performed. The patients were divided into two groups based on their immunosuppressive protocol. Group I was treated with Cyclosporin A (CsA) and group II with azathioprin. A compensatory hypertrophy with a volume increase of 20% could be seen in nearly all grafts. During acute tubular necrosis only minimal sonographic changes could be found. In each group 16 patients developed an acute rejection episode. Sonographic signs of acute rejection were: (1) a hypoechoic enlargement of the renal pyramides; (2) an increase in cortical echogenicity; (3) an increase in graft volume greater than compensatory hypertrophy; (4) an indistinct parenchyma-pelvic border; (5) dilation of the pelvis with a parenchyma-pelvic index greater than 2.3:1 (in group II cases). Chronic rejection is characterized by graft shrinkage. No specific signs were evident. The increasing use of CsA diminishes the value of sonography in follow up of acute rejection after kidney transplantation. Nevertheless, it is of great value for follow-up examination concerning other complications. PMID- 1871675 TI - The cholecystogastric fistula. AB - Internal gall bladder fistulas with a hollow viscus following dislocation of a gallstone into the intestine represent one of the late sequelae of cholelithiasis. We report the case of a 78-year-old patient, who suffered from a cholecystogastric fistula with consecutive stone transmigration into the stomach. PMID- 1871676 TI - Easy, non-traumatic insertion of a transparent overtube during endoscopic esophageal surgery. PMID- 1871677 TI - Early and long-term results of pneumatic dilation in the treatment of oesophageal achalasia. AB - Between 1967 and 1989, 60 patients underwent pneumatic dilation of the cardia at our institution. Of these, 33 had not undergone any previous treatment (group 1), whereas 27 presented with recurrent dysphagia after a failure of surgical treatment (group 2). In this series there was no procedure-related mortality and a perforation occurred only in 1 patient who was treated conservatively. The mean follow-up was similar in both groups (44 and 49 months, respectively). The results of pneumatic dilation were either excellent or good in 61% of group 1 patients, and in 76% of group 2 patients. Reflux oesophagitis requiring medical therapy occurred in 1 group 2 patient. We conclude that pneumatic dilation is a safe and relatively effective procedure in patients with achalasia. Patients with a failed Heller myotomy seem to respond better than patients without previous surgery. However, the risk of gastro-oesophageal reflux after pneumatic dilation should not be underestimated. PMID- 1871678 TI - Two dynamic modes of striatal function under dopaminergic-cholinergic control: simulation and analysis of a model. AB - A neural network model based on the anatomy and physiology of the matrix compartment of the striatum is described. The model consists of a network of neurons which are mutually inhibitory within a defined domain. A membrane potassium conductance (GK) under dopaminergic-cholinergic control is included in the model. Computer simulation results show that changes in GmaxK can modulate the behaviour of the network to produce either competition or coactivation among striatal output neurons. An analysis of a two-neuron system based on the model shows that the maximum steepness of the threshold function plays a decisive role in the dynamics, in particular with regard to the competition that exists between the neurons. Competitive interactions predominate at low GmaxK, while coactivation predominates at high GmaxK. We suggest that the former dynamic governs reciprocal inhibition of antagonistic muscles, while the latter governs cocontraction and rigidity. The model offers insights into the control of striatal neurodynamics by GmaxK which establish closer links between dopaminergic actions in the striatum and the mechanism of Parkinsonian rigidity. A prediction of the model is that acetylcholine should increase GKmax in striatal output neurons. PMID- 1871679 TI - GABA depolarizes neurons in the rat striatum: an in vivo study. AB - GABA, applied by iontophoresis to striatal neurons of the rat in an in vivo preparation, depolarized the membrane potential and decreased the input resistance in a dose-dependent manner. The null potential of the GABA depolarization was about -50 mV. In addition, a fading of the GABA-induced response was observed for prolonged and relatively high amino acid application. We conclude that GABA has a depolarizing effect on striatal cells. This is in line with recent in vitro works describing a depolarizing effect of GABA in the rat neostriatum. PMID- 1871680 TI - Age-related remodeling of glutamic-acid decarboxylase-labeled elements in deafferented piriform cortex of rats. AB - Olfactory bulb (OB) removal has been shown to result in plasticity in the piriform cortex (PC) that is age dependent. We are studying this phenomenon using immunoelectron microscopy of glutamic acid decarboxylase immunoreactivity (GAD, the enzymatic precursor for GABA) at selected postnatal ages and in adults with emphasis on short survival times of 4-7 days after OB ablation. Normally GAD labeled synaptic terminals form type II symmetric contacts onto unlabeled dendrites and GAD-labeled dendrites receive type I, asymmetric contacts from unlabeled terminals (Westenbroek, et al., 1988a). The OB lesion results in degenerating terminals with type I contacts onto unlabeled and onto GAD-labeled dendrites. Type I postsynaptic sites may be seen partially contacted by or entirely devoid of degenerating terminals and occasionally may be apposed to variable degrees by normal unlabeled or by GAD-positive terminals. Subsequently, some GAD-labeled terminals may form asymmetric type I contacts usually with unlabeled dendrites and rarely with GAD-labeled dendrites. The findings are most common in the youngest subjects and essentially absent in the adult subjects. A sequence of reinnervation of deafferented type I sites by GAD-labeled terminals is suggested for the formation of this "atypical" synapse and the sequelae of this reorganization are discussed. PMID- 1871682 TI - [Medical problems in the care of the elderly]. AB - The number of long-lived persons is increasing dramatically. They have a high need for medical help and make high demands on their doctors, especially because of their extreme physical, psychological and social multimorbidity. It is difficult but important to assess the vital energy and the life expectancy of these persons living near death. The spectrum of vitality ranges from admirably well-preserved persons without any need of help to bedridden sick people wasting away. In this paper, there are discussed specific findings and opportunities of intervention, in particular the problems of admission to hospital and life lengthening measures. PMID- 1871681 TI - Differential changes in mRNAs encoding for preprotachykinin A and B after kainic acid-induced seizures in the rat. PMID- 1871683 TI - [Falls of elderly people--a systematic evaluation is necessary]. AB - Falls of the elderly represent a real challenge for both the physician who is called in order to evaluate the causes and consequences of a trauma and the patient who is menaced in his physical and mental integrity. But falls question also the family who feels insecure and guilty as well as society, which sees itself confronted with the rising cost induced by the request of services and institutions. Only a systematic approach, considering factors of surroundings, will allow us an exhaustive evaluation of each individual patient and will, on the other hand, enable us to foresee, beyond the introduction of therapy, preventive measures. In the present article a proposal is made for a predominantly clinical evaluation in the perspective of general health promotion. In this way a fall can also become an occasion for the patient to rethink in a useful way the necessary reorganization of his own life, which in the course of years is dominated more and more by the aspiration for security. PMID- 1871684 TI - [Evaluating gait disorders in geriatrics]. AB - Gait disorders in the elderly are a major cause of falls and accidents. They also interfere badly with the quality of life and the psychosocial well-being. The prevalence of these disorders is very high: 15% of the persons over 65 years and about 25% of those over 75 years suffer from gait disorders. The cause of gait disorders can be a specific disease, but in the elderly, multiple causes are much more frequent. In the elderly, the analysis of gait disorders consists not only of a diagnostic work-up, but also of a comprehensive geriatric and functional gait assessment. A minimal gait assessment includes a special clinical examination, an instrumental analysis of gait speed and a functional assessment of gait and balance by standard tests. In this article the relevant methods of a practical gait assessment are presented and some basic aspects of treatments are discussed. PMID- 1871685 TI - [Rehabilitation of over 60-year-old stroke patients]. AB - The rehabilitation processus in over 60-year-old patients is documented. History, clinical findings and progress of rehabilitation in 289 patients were evaluated. A pre- and post-comparison and a subgroup formation on the basis of rehabilitation success and finally the evaluation of possible predicting factors for the rehabilitation success are presented. "Successful rehabilitation" was defined, based on the clinical outcome, and judged by the responsible physician. This decision was subjected to thorough analysis. The outcome was judged to be 'very successful' in 18.3%, 'successful' in 51.2% and 'not successful' in only 30.5%. The costs per case were 16,000 DM. Highly significant relationships could be found between the expression 'successful rehabilitation', the discharge lacation, the stage of care at the time of discharge, the Barthel index and the in-house hemiplegic status at discharge. The following conditions resulted as highly significant predictors: stage of car, general condition, the numeric value of the Barthel index, presence of incontinence and presence of a psychoorganic syndrome. Age, sex and number of strokes revealed no relationship to the rehabilitation success in this work. In spite of multiple morbidity and in spite of mobility restrictions and prolonged reconvalescence time, the geriatric rehabilitation carried out in a trained team is successful. PMID- 1871686 TI - [Diagnosis, prevention and therapy of osteoporosis]. AB - Osteoporosis is a generalized osteopathy manifesting itself mainly in women beyond 60 years of age. We still lack a uniform definition of osteoporosis, generally defined as a decrease in bone mass in comparison with an age- and sex related norm with normal mineralization of the remaining bone tissue. Of great importance for diagnosis are, above all, radiological procedures (plain X-rays of the spine, photon absorptiometry, computerised tomography), besides the medical history (backache, fractures) and the physical examination (kyphosis, shortening of the trunk, decrease in height). Furthermore, analyses of clinical chemistry and eventually histological examinations have to be applied for differential diagnostics with other generalized osteopathies and for etiological classification. The therapy of osteoporosis is supported by two main components: therapy of pain and influence on bone metabolism in order to diminish the risk of fractures. The position of fluorides in the treatment of osteoporosis is still under discussion. Most recent results recognize an alternative possibility by use of diphosphonates. Hormone substitution, physical training and nutritional aspects come to the fore in the prophylaxis of osteoporosis. PMID- 1871687 TI - [Significance of arrhythmias in advanced age]. AB - Tachycardiac and bradycardiac arrhythmias increase with age. Because cardiac arrhythmias at an advanced age are almost always caused by organic disease, one must face more frequently electrical complications (e.g. ventricular fibrillation). Owing to the decrease of arterial flow volume as well as mean arterial pressure, bradycardiac and tachycardiac arrhythmias result in cerebral symptoms more often in elderly than younger persons. The causes of this observation are the disturbed cerebral autoregulation of blood pressure, but also the insufficient capacity of adaptation of the ageing circulation. In this situation it is more frequently necessary in old people than in younger ones to treat cardiac arrhythmias by antiarrhythmic drugs. The cardiodepressant effect of most antiarrhythmic drugs must be taken into account in this context. PMID- 1871688 TI - [Decubitus ulcers in geriatrics--pathogenesis, prevention and therapy]. AB - Magnitude and duration of interface pressure are the crucial etiological factors in the decubitus ulcer formation. Small amounts of interface pressure that exceed the average capillary pressure (range: 2.7 to 6.3 kPa) may lead to compression of the skin microcirculation and resultant tissue necrosis when a critical duration of interface pressure of more than 2 h is reached. The principles of decubitus ulcer prevention are derived from the pathophysiology of ulcer formation as noted: reduction of interface pressure below 3 kPa by bedding each at-risk patient on a 'super-soft' mattress and shortening the duration of interface pressure below 2 h. by turning of patients from the supine position to the right and left 30 degrees oblique back position every two hours. Decubitus ulcers typically show impaired wound healing. Conditions most conspicuously protracting normal wound healing are: tissue hypoxia, fibrin deposits, necrotic tissue, local infection, defective migration of keratinocytes, impaired general condition, etc. Based on these pathophysiological mechanisms, five therapeutical principles are proposed: complete relief of interface pressure, debridement of necrotic tissue, treatment of infection using systemical antibiotics, wet and air-permeable wound dressing, improvement of patient's general condition. PMID- 1871689 TI - [Value of surgical treatment of decubitus ulcer in geriatric patients]. AB - Geriatric patients have a high incidence of pressure sores. Pain, chronic and acute infection and protein loss may impair their general condition. Pressure relief, local debridement, disinfection and physiologic wound dressing are the first steps in local treatment. The spontaneous healing time of a pressure sore is very slow, even if concomitant diseases as diabetes, urinary tract infection and pneumonia could be stabilized and the general condition of the patient be improved. In these selected and stable cases, surgical debridement and plastic pressure sore closure may be indicated. Simple skinflaps can give good results in superficial sores without bone involvement and have a low operative morbidity. Musculocutaneous flaps are technically more difficult, but resist better to infection and may fill bigger and deeper defects. In any operation, vascular territories (angiosomes) of further flaps, suitable for a recurrent or second decubitus closure, must be preserved. Long-term results in 30 operated patients over 60 are presented. Although the postoperative complication rate is very high, healing could be achieved in all surviving patients. PMID- 1871690 TI - Risk of tuberculosis in immigrant Asians: culturally acquired immunodeficiency? AB - Study of the 620 Asian immigrants with tuberculosis notified in the Wandsworth area of south London between 1973 and 1988 showed a bimodal pattern of tuberculosis notifications: in 1977 there was a peak among Asians from East Africa, and in 1981 a peak among those from the Indian subcontinent. There was a mean lag time of five years between clinical presentation and immigration. Logit analysis showed that, although overall more men had tuberculosis than women, glandular tuberculosis was more common among women of all groups, and pulmonary tuberculosis was more common among Hindu women than Hindu men. Both subgroups of Asians had a substantially higher incidence of tuberculosis than white people, particularly at extrapulmonary sites. Hindus were also at a significantly greater risk of tuberculosis at all sites than Muslims (Hindu:Muslim risk ratio 5.5 for women and 3.7 for men). The increased susceptibility to tuberculosis of Hindus, particularly Hindu women, may be related to a culturally acquired immunodeficiency caused by vegetarianism and associated vitamin deficiency. PMID- 1871691 TI - Corticosteroid treatment as a risk factor for invasive aspergillosis in patients with lung disease. AB - Invasive pulmonary aspergillosis usually occurs in severely immunocompromised or neutropenic patients. Six patients with invasive aspergillosis are described whose only defence impairment was underlying lung disease and corticosteroid treatment. Cough, fever, and sputum production were the usual reasons for presentation and four patients developed the sepsis syndrome. Radiographic findings included de novo cavitation in three patients and rapid radiographic progression in four. Aspergillus species were isolated from respiratory secretions of all patients early in the course of the disease. Treatment was effective in only two patients and the subsequent progress of the others was consistent with a chronic necrotising process. Invasive pulmonary aspergillosis is uncommon in patients with respiratory diseases receiving corticosteroids, but should be considered when pneumonia and cavitary infiltrates occur. PMID- 1871692 TI - Continuous extrapleural intercostal nerve block after pleurectomy. AB - A randomised, double blind trial was carried out in 16 patients undergoing pleurectomy to assess the effect of continuous extrapleural intercostal block on postoperative pain and pulmonary function. Subjective pain relief was assessed on a linear visual analogue scale. Pulmonary function was measured on the day before operation and daily for five days after surgery. Eight patients received bupivacaine and eight placebo (saline). The mean pain scores at 4, 8, 16, and 24 hours were 13.3, 8.5, 6.1, and 10 mm respectively in the bupivacaine group compared with 56.3, 41, 46.7, and 35 in the control group; in addition, the bupivacaine group required less papaveretum. Twenty four hours after surgery mean values of peak expiratory flow, forced expiratory volume in one second, and forced vital capacity were reduced to 82%, 76%, and 76% of preoperative control values in the bupivacaine group, and to 39%, 32%, and 36% in the control group. The speed of recovery of pulmonary function was superior in the bupivacaine group. There were no complications related to the infusion. Continuous extrapleural intercostal nerve blockade with bupivacaine provides safe and effective postoperative analgesia and improves respiratory mechanics after pleurectomy. PMID- 1871693 TI - Erythropoietin concentrations in obstructive sleep apnoea. AB - Eight patients with obstructive sleep apnoea and a normal haemoglobin concentration underwent nocturnal studies during which oxyhaemoglobin saturation was recorded continuously with an ear oximeter and serum erythropoietin concentration was measured hourly by means of a radioimmunoassay. Serum erythropoietin concentrations remained within the normal range throughout the study despite falls in oxyhaemaglobin saturation in individuals to 33-78%. There was no relation between the degree of nocturnal hypoxaemia and serum erythropoietin concentrations. The brief cyclical episodes of hypoxaemia typical of obstructive sleep apnoea may not be a sufficient stimulus for erythropoietin secretion. PMID- 1871694 TI - Abnormal lung function associated with asbestos disease of the pleura, the lung, and both: a comparative analysis. AB - The impairment of lung function associated with different types of asbestos related disease was examined in 1298 men. The 310 men with circumscribed pleural lesions (plaques) or diffuse pleural thickening without asbestosis were compared with 596 men with asbestosis only and with 322 men with pleural abnormalities and asbestosis, as classified from chest radiographs by ILO pneumoconiosis criteria. Spirometric indices and total lung capacity (TLC; determined by planimetry) were measured and expressed as percentages of predicted values. Non-smoking men with pleural disease only had reduced values of mid and terminal expiratory flows (80.6 and 69.9% predicted) and a reduced FEV1 (89% predicted) with a forced vital capacity (FVC) of 94% predicted. TLC was 104% predicted. Thus they had airways obstruction with-out restriction. Non-smoking men with pulmonary asbestosis (ILO profusion of opacities mostly 1/0 and 1/1) had pulmonary function similar to that of men with pleural disease. FEV1 and FVC and flow rates at other lung volumes were lower in smokers with asbestosis (after adjustment for duration of smoking) than in the non-smokers with asbestosis. Airflow limitation was worse in the men with both pleural abnormalities and pulmonary asbestosis with lower values for mid expiratory flow, FEV1 and FVC (but not TLC) than those with either abnormality alone, in both non-smokers and current smokers. Men with diffuse pleural thickening that included the costophrenic angles had more airways obstruction and air trapping and lower FVC values than those with circumscribed pleural disease. PMID- 1871695 TI - Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine. AB - N-acetylcysteine (600 mg/day) was given to patients by mouth for five days before bronchoscopy and bronchoalveolar lavage to determine whether N-acetylcysteine could increase the concentrations of the antioxidant reduced glutathione in plasma and bronchoalveolar lavage fluid. Bronchoalveolar lavage was performed 1-3 hours (group 2, n = 9) and 16-20 hours (group 3, n = 10) after the last dose of N acetylcysteine and the values were compared with those in a control group receiving no N-acetylcysteine (group 1, n = 8). N-acetylcysteine was not detected in plasma or lavage fluid. Plasma concentrations of cysteine, the main metabolite of N-acetylcysteine and a precursor of reduced glutathione, were greater in the groups receiving treatment (groups 2 and 3) than in group 1. Cysteine concentrations in lavage fluid were similar in the three groups. Concentrations of reduced glutathione were greater in both plasma and lavage fluid in group 2 than in group 1. These data suggest that N-acetylcysteine given by mouth is rapidly deacetylated to cysteine, with resulting increases in the concentrations of cysteine in plasma and of reduced glutathione in plasma and the airways, which thus temporarily increase the antioxidant capacity of the lung. PMID- 1871696 TI - Cystic fibrosis. 3. Cloning the cystic fibrosis gene: implications for diagnosis and treatment. PMID- 1871697 TI - Assisted ventilation. 4. Weaning from mechanical ventilation. PMID- 1871698 TI - Peripheral mucoepidermoid tumour of the lung. AB - Mucoepidermoid tumours of the bronchial tree are uncommon neoplasms, which are believed to arise from terminal ducts of the proximal tracheobronchial tree. The first case of a peripheral mucoepidermoid tumour of the lung is reported. PMID- 1871699 TI - Anti-basement membrane antibody disease with severe pulmonary haemorrhage and normal renal function. PMID- 1871700 TI - Bronchography in the assessment of patients with lung collapse for endoscopic laser therapy. PMID- 1871701 TI - Value of washings and brushings at fibreoptic bronchoscopy in the diagnosis of lung cancer. PMID- 1871702 TI - Transcarinal needle aspiration in the diagnosis of mediastinal adenitis in a patient infected with the human immunodeficiency virus. PMID- 1871703 TI - Horner's syndrome occurring as a complication of pleurectomy. PMID- 1871704 TI - Malignant carcinoid tumour of the oesophagus. PMID- 1871706 TI - Immunological detection of activated platelets in clinical disorders. PMID- 1871705 TI - The protective effect of a beta 2 agonist against excessive airway narrowing in response to bronchoconstrictor stimuli in asthma and chronic obstructive lung disease. AB - Beta 2 agonists reduce airway hypersensitivity to bronchoconstrictor stimuli acutely in patients with asthma and chronic obstructive lung disease. To determine whether these drugs also protect against excessive airway narrowing, the effect of inhaled salbutamol on the position and shape of the dose-response curves for histamine or methacholine was investigated in 12 patients with asthma and 11 with chronic obstructive lung disease. After pretreatment with salbutamol (200 or 400 micrograms) or placebo in a double blind manner dose-response curves for inhaled histamine and methacholine were obtained by a standard method on six days in random order. Airway sensitivity was defined as the concentration of histamine or methacholine causing a 20% fall in FEV1 (PC20). A maximal response plateau on the log dose-response curve was considered to be present if two or more data points for FEV1 fell within a 5% response range. In the absence of a plateau, the test was continued until a predetermined level of severe bronchoconstriction was reached. Salbutamol caused an acute increase in FEV1 (mean increase 11.5% predicted in asthma, 7.2% in chronic obstructive lung disease), and increase in PC20 (mean 15 fold in asthma, fivefold in chronic obstructive lung disease), and an increase in the slope of the dose-response curves in both groups. In subjects in whom a plateau of FEV1 response could be measured salbutamol did not change the level of the plateau. In subjects without a plateau salbutamol did not lead to the development of a plateau, despite achieving a median FEV1 of 44% predicted in asthma and 39% in chronic obstructive lung disease. These results show that, although beta 2 agonists acutely reduce the airway response to a given strength of bronchoconstrictor stimulus, they do not protect against excessive airflow obstruction if there is exposure to relatively strong stimuli. This, together with the steepening of the dose response curve, could be a disadvantage of beta 2 agonists in the treatment of moderate and severe asthma or chronic obstructive lung disease. PMID- 1871707 TI - No evidence of HIV-1 infection in seronegative hemophiliacs and in seronegative partners of seropositive hemophiliacs through polymerase chain reaction (PCR) and anti-NEF serology. AB - We prospectively studied a well-characterized cohort including 60 seronegative hemophiliacs or von Willebrand's disease patients, 6 seronegative female sexual partners of seropositive hemophiliacs, 59 seropositive hemophiliacs or von Willebrand's disease patients and 2 seropositive partners of seropositive hemophiliacs (used as positive controls), and 117 seronegative low risk individuals (used as negative controls). PCR assay, performed in peripheral blood mononuclear cells using three primer pairs in the gag, pol, LTR regions, showed no positive results in the 60 seronegative patients, in the 6 seronegative partners of seropositive patients and in the 117 seronegative low risk individuals, while PCR was positive with at least one primer pair in 53 (87%) of 61 seropositive patients. Anti-nef serology (Western-blot) was negative in seronegative patients, in seronegative partners of seropositive patients and positive in 58% out of the seropositive individuals. These results strongly suggest an absence of HIV-1 infection in individuals with a lastingly negative HIV serology. PMID- 1871708 TI - Variation in the promoter region of the beta fibrinogen gene is associated with plasma fibrinogen levels in smokers and non-smokers. AB - We investigated the association between fibrinogen levels and a HaeIII restriction fragment length polymorphism located at -453 bp from the start of transcription of the beta fibrinogen gene. 292 healthy men aged 45 to 69 years, recruited from general practices throughout Britain, were studied. None had a history of ischaemic heart disease. 41.1% (120) were smokers and fibrinogen levels were higher in this group. The frequency of the non-cutting allele (designated H2) was 0.19 and was the same in smokers and non-smokers. The H2 allele was associated with elevated levels of fibrinogen in both smokers and non smokers and the effect of genotype was similar in both groups. After smoking, HaeIII genotype was the strongest predictor of fibrinogen levels and explained 3.1% of the variance in fibrinogen levels. These results confirm earlier studies that variation at the fibrinogen locus contributes to the between-individual differences in plasma fibrinogen level. PMID- 1871709 TI - Acquired disorder of platelet function associated with autoantibodies against membrane glycoprotein IIb-IIIa complex--1. Glycoprotein analysis. AB - A patient with idiopathic thrombocytopenic purpura developed after splenectomy a thrombasthenia-like severe haemorrhagic diathesis characterized by a normal or subnormal platelet count, prolonged bleeding time, strongly reduced platelet adhesion to glass and defective platelet aggregation in response to ADP and collagen. In contrast to hereditary thrombasthenia membrane glycoproteins (GP) IIb and IIIa were normally present in the patient's platelets. Immunoelectrophoretic analysis revealed an abnormal behaviour of the patient's GP IIb-IIIa complex. Autoantibodies against GP IIb-IIIa were detected in Triton extracted washed platelets. Incubation of normal platelets with plasma from the patient resulted in a similar immunoelectrophoretic abnormality of the GP IIb IIIa complex indicating that bound autoantibodies (IgG) are responsible for the abnormal immunoelectrophoretic behaviour of the patient's GP IIb-IIIa complex. Platelet fibrinogen was severely reduced similar to classical thrombasthenia suggesting that the GP IIb-IIIa complex is involved in platelet fibrinogen storage. PMID- 1871710 TI - Studies on the contact system of coagulation during therapy with high doses of recombinant IL-2: implications for septic shock. AB - Patients treated with high doses of interleukin-2 (IL-2) because of cancer, develop hemodynamic and vasopermeability changes, that resemble those observed in sepsis. These patients thus provide a unique opportunity to study the early events in the development of septic shock. We analysed the changes that occurred in the contact system of coagulation in plasma from 4 patients, who together received seven 12-day cycles of high doses of IL-2. Levels of factor XII and prekallikrein during the cycles progressively fell to 50 and 30% of their initial levels, respectively, whereas significant increases in plasma factor XIIa- and kallikrein-C1-inhibitor complexes were not observed (in 3 out of 211 samples slightly increased levels of both complexes were found). The reductions in factor XII and prekallikrein were only in part due to protein leakage, since levels were still significantly lower, i.e., 80 and 50%, respectively, when corrected for albumin decreases. Levels of high molecular weight kininogen (HMWK) also decreased during IL-2 therapy, however, this decrease paralleled that of albumin. SDS-PAGE analysis of plasma HMWK did not reveal increased cleavage of this protein. The reduction of factor XII and prekallikrein, corrected for protein leakage, significantly correlated with albumin levels and inversely with daily cumulative weight gain in the patients. Thus, we demonstrate that factor XII and prekallikrein decrease during IL-2 therapy. As these decreases, already observed after 1 day treatment, were disproportional to that of albumin, a negative acute phase reactant, and correlated with signs of the vascular leak syndrome, we favor the explanation that they reflected activation rather than a decreased synthesis of the contact system proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871711 TI - Benefit/risk profile of combined antiplatelet therapy with ticlopidine and aspirin. AB - Ticlopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 microM; adrenaline 0.75-2.5 microM; collagen 1.5-150 micrograms/ml; arachidonic acid 1 mM; PAF 1 microM; adrenaline 0.17 microM + ADP 0.62 microM; serum thromboxane [( TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p less than 0.05) than either treatment alone in depressing responses to high dose collagen (% over control, mean +/- SEM: T: 95 +/- 3; ASA: 96 +/- 5; T + ASA: 89 +/- 4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871712 TI - Three distinct point mutations in the factor IX gene of three Japanese CRM+ hemophilia B patients (factor IX BMNagoya 2, factor IX Nagoya 3 and 4). AB - Enzymatic DNA amplification and complete sequence analysis were used to investigate human factor IX coding sequences in three CRM+ hemophilia B patients. In a patient with severe hemophilia B and a markedly prolonged ox-brain prothrombin time, a C to T transition in exon VI changed the codon for Arg180 to Trp (factor IX BMNagoya 2). This mutation would impair the cleavage by factor XIa required for activation of the zymogen. In a patient with mild hemophilia B, a G to A transition in exon VI changed the codon for Arg145 to His(factor IX Nagoya 3). This substitution also would be predicted to preclude the cleavage of factor IX by factor XIa at this peptide bond (Arg145-Ala146). Furthermore, this point mutation creates a new NlaIII restriction site which provides a quick and reliable method for carrier detection in the affected family members. A patient with severe hemophilia B (factor IX Nagoya 4) had a G to A transition in exon II changing the codon for Glu21 to Lys. This novel point mutation is assumed to impair the function of factor IX by disrupting the calcium binding of factor IX. PMID- 1871713 TI - High level expression of recombinant human tissue factor in Chinese hamster ovary cells as a human thromboplastin. AB - Tissue factor (TF) is the high affinity transmembrane receptor and cofactor for cellular initiation of the plasma coagulation protease cascades by factor VIIa. We describe the synthesis of recombinant huTF by stably transfected CHO cell lines carrying integrated huTF DNA, and the isolation of huTF glycoprotein with specific functional activity equivalent to natural huTF. The expression vector (pCDM8), carrying the cytomegalovirus promoter to drive transcription of a partial cDNA construct encoding the complete huTF protein chain, was cotransfected with a plasmid containing the neomycin resistance gene for selection. These clones were further selected for level of expression of huTF protein. Optimal expression compatible with stability and cell growth was approximately 13.5 x 10(6) molecules per cell. To our knowledge, this is one of the highest levels of expression described for a recombinant transmembrane receptor in mammalian cells. Recombinant huTF protein was obtained by single-step immuno-affinity purification, and exhibits heterogeneity due to N-linked glycosylation. The protein was indistinguishable from natural huTF based on functional properties of the glycoprotein reconstituted in lipid vesicles, and expression of conformational epitopes. Large scale production of recombinant huTF is feasible to permit basic studies of protein structure as well as for design of huTF thromboplastin reagents. PMID- 1871714 TI - Inhibition of recombinant human blood coagulation factor VIIa amidolytic and proteolytic activity by zinc ions. AB - Although it is well established that calcium is an essential cofactor in blood coagulation, recent experimental evidence suggests that zinc may also play an important role in hemostasis. In the present study, we have examined the effect of zinc ions on the amidolytic and proteolytic activity of recombinant factor VIIa in the presence of physiological levels of calcium ions. The amidolytic activity of factor VIIa was inhibited half-maximally by 20 microM zinc. The amidolytic activity of a derivative of factor VIIa lacking the gamma carboxyglutamic acid domain was also inhibited half-maximally by 20 microM zinc, suggesting that the mechanism of zinc inhibition of factor VIIa amidolytic activity did not involve its gamma-carboxyglutamic acid residues. The amidolytic activity of a complex of recombinant tissue factor and factor VIIa was inhibited half-maximally by 70 microM zinc. In contrast to the results obtained with factor VIIa, the amidolytic activities of other human vitamin K-dependent coagulation proteases including factor Xa, thrombin and activated protein C were not appreciably affected by 50-100 microM zinc. The proteolytic activation of factor X by a complex of factor VIIa and relipidated tissue factor apoprotein was inhibited half-maximally by 40 microM zinc, whereas activation of factor IX in this system was inhibited half-maximally by 70 microM zinc ions. Considerably higher levels of zinc (approximately 100 microM) were required to inhibit half maximally the rate of factor X activation by a complex of factor VIIa and functional tissue factor on the surface of either a human bladder carcinoma cell line, J82, or stimulated human umbilical vein endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871715 TI - A photometric assay for blood coagulation factor XIII. AB - An assay for a direct photometric determination of F XIII in untreated and undiluted plasma was developed. In a one-step procedure F XIII is activated by thrombin and Ca2+ and cross-links glycine-ethylester to a specific glutamine containing peptide substrate. The released ammonia is incorporated into alpha ketoglutarate by glutamate dehydrogenase, and the NADH consumption of this reaction is measured photometrically at 340 nm. NADH-consumption is directly proportional to the F XIII activity. Fibrin polymerization and the corresponding turbidity is avoided by the use of a fibrin aggregation inhibitor. The procedure is rapid and simple and enables to measure within the range of 0 to 150% F XIII. It can be performed with automated analyzers as well as with common photometric equipment. The normal range of F XIII activity in 167 healthy donors was determined to be 70 to 140%. PMID- 1871716 TI - Cellular localization of activated factor X by Xa-specific probes. AB - A probe, recombinant antistasin, that reacts specifically with the activated form of factor X (Xa) was used in immunohistochemical procedures to detect cellular sites of Xa generation within intact tissues. Factor Xa was detected on tumor cells in small cell carcinoma of the lung, renal cell carcinoma, and malignant melanoma. Tumor-associated macrophages (but not tumor cells) expressed Xa in adenocarcinoma and squamous cell carcinoma of the lung, and Hodgkin's disease. Factor Xa in these locations corresponded to evidence reported previously for an intact coagulation pathway and thrombin formation associated with these tumor cells and macrophages. By contrast, only rare connective tissue cells stained for Xa in breast and colon cancer, tumor types shown previously to lack an intratumoral coagulation pathway and thrombin generation, and in normal liver, lung, breast, kidney, and placental tissues. Hepatocytes did not stain. These results suggest that such probes may be useful for studying the activation state of cell-associated factor X in situ within intact tissues. PMID- 1871717 TI - Dependence of blood clot lysis on the mode of transport of urokinase into the clot--a magnetic resonance imaging study in vitro. AB - Magnetic resonance imaging was employed to study the dependence of clot lysing patterns on two different modes of transport of urokinase into whole blood clots. In one group of clots (nonperfused clots, n1 = 10), access of urokinase to the fibrin network was possible by diffusion only, whereas in the other group (perfused clots, n2 = 10) bulk flow of plasma containing urokinase was instituted through occlusive clots by a pressure difference of 3.7 kPa (37 cm H2O) across 3 cm long clots with a diameter of 4 mm. It was determined separately that this pressure difference resulted in a volume flow rate of 5.05 +/- 2.4 x 10(-2) ml/min through occlusive clots. Perfused clots diminished in size significantly in comparison to nonperfused ones already after 20 min (p less than 0.005). Linear regression analysis of two-dimensional clot sizes measured by MRI showed that the rate of lysis was more than 50-times faster in the perfused group in comparison to the nonperfused group. It was concluded that penetration of the thrombolytic agent into clots by perfusion is much more effective than by diffusion. Our results might have some implications for understanding the differences in lysis of arterial and venous thrombi. PMID- 1871718 TI - The effect of agonists and antagonists of platelet aggregation on von Willebrand factor-mediated platelet agglutination. AB - Ristocetin-induced platelet agglutination (RIPA) in EDTA-treated citrated platelet-rich plasma was reduced to 49 +/- 11% by 1.25 microM ADP, 41 +/- 14% by 1 microM A23187, and 26 +/- 7% by 0.1 microgram/ml platelet activating factor (PAF). The effect of 5-110 microM epinephrine was not dose-dependent, but varied between donors, with RIPA from 56-100% of the control. The inhibitory effects of these agonists were not altered by prior treatment of platelets with aspirin. Prior addition of 200 microM ATP (an ADP receptor antagonist acting at both high and low affinity ADP receptors) prevented the inhibitory action of ADP but not that of A23187 or PAF, suggesting that the inhibitory actions of the latter are not mediated by released ADP. As 700 microM 8-bromoadenosine 5-diphosphate (an ADP receptor antagonist acting mainly at the high affinity receptor) did not prevent ADP-induced inhibition of RIPA, interaction of ADP with the low affinity receptor is presumably responsible for its inhibitory action. As A23187, but not phorbol myristate acetate (0.1 microM) inhibited RIPA, an increase in intracellular calcium ions rather than direct stimulation of protein kinase C appears to mediate agonist-induced inhibition. Cytochalasin B (10.5-21 microM), dibucaine (0.5-1 mM), and prostaglandin E1 (25 nM), added before or after the agonist, prevented or reversed ADP-, A23187-, and PAF-induced inhibition of RIPA, suggesting that the state of the platelet cytoskeleton affects inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871719 TI - Thromboxane responsiveness of dog platelets is inherited as an autosomal recessive trait. AB - Most mongrel dogs have platelets that form thromboxane A2 (TXA2) from exogenous arachidonate, but they fail to aggregate or secrete in response to it. In contrast to these TXA2 insensitive (TXA2-) platelets, some dogs have TXA2 sensitive (TXA2+) platelets that aggregate and secrete when stirred with arachidonate. To evaluate the possible genetic basis for this difference, we carried out seven matings of mongrel dogs that yielded 48 viable offspring. Four matings of dogs with TXA2- platelets (presumed genotype TT) including 2 back crosses, produced 32 pups with TXA2- (TT) platelets and 0 pups with TXA2+ platelets. A cross between a male with TXA2+ platelets (presumed genotype tt) and a female with TXA2+ (tt) platelets yielded 9 offspring with TXA2+ (tt) platelets and 0 with TXA2- platelets. Crossing a male presumed homozygous (TT) for TXA2- platelets with a female with TXA2+ (tt) platelets produced 2 pups with TXA2- (Tt) platelets and 0 pups with TXA2+ (tt) platelets. The same female with TXA2+ platelets crossed with a male presumed to be heterozygous (Tt) for TXA2- platelets yielded 2 pups with TXA2+ (tt) platelets and 3 pups with TXA2- (Tt) platelets. Segregation analysis of these data supports the hypothesis that the ability of dog platelets to aggregate and secrete in response to TXA2 is inherited as an autosomal recessive trait. PMID- 1871720 TI - Platelets adhere to sulfatides by von Willebrand factor dependent and independent mechanisms. AB - Unstimulated human platelets from normal volunteers adhere to sulfatides (galactosylceramide-I3-sulfate) as single cells but do not adhere appreciably to other lipids including gangliosides, neutral glycolipids, phospholipids or cholesterol-3-SO4. Platelet adhesion to sulfatide is saturable and dose dependent, reaches maximal levels in 90 to 120 min, and is not divalent cation dependent. Because sulfatides bind von Willebrand factor (vWf) with specificity and high affinity and platelet adhesion to structurally related sulfated glycolipids is approximately proportionate to their ability to bind vWf, we examined whether vWf mediates platelet adhesion to sulfatides. Platelets from a patient with severe Type I von Willebrand's disease adhere poorly to sulfatides. However, adhesion to levels seen with normal platelets is restored by the addition of vWf. Adhesion of normal platelets can be partially inhibited by a monospecific antibody to vWf. Normal platelet adhesion to sulfatides, however, is not increased following preincubation with vWf. Both vWf binding and platelet adhesion to sulfatides can be inhibited by the sulfated polysaccharide dextran sulfate at low concentration, fucoidan at high concentrations, but not by heparin, fibrinogen, fibronectin, or the synthetic peptides Gly-Arg-Gly-Asp-Ser Pro or Gly-Arg-Gly-Glu-Ser-Pro. Thus, adhesion to sulfatides appears to be of two types; vWf dependent (50-75%) and vWf independent (25-50%). PMID- 1871721 TI - Evaluation of pulmonary accumulation of 51chromium-labelled rat platelets following intravenous application of ADP and collagen. AB - We examined the effects of ADP- and collagen-induced pulmonary platelet embolism in the rat. Homologous 51Chromium-labelled platelets were used to monitor extracorporally the distribution of platelets in the circulation. For that purpose, collimated iodide scintillation detectors were placed above thorax (C1) and abdomen (C2). A dose-dependent increase in thoracic radioactivity, paralleled by a decrease in the abdomen, was observed after intravenous injection of ADP and collagen. This resulted in a shift of C1/C2, so that the effect of collagen was more pronounced (maximal increase of C1/C2 = 134%) than ADP (maximal increase of C1/C2 = 79%). The increase in thoracic radioactivity was caused by the uptake of platelets in the lung as was shown after administration of collagen (6-fold enrichment of labelled platelets). Lung platelet sequestration resulted in a dose dependent thrombocytopenia. The ADP -and collagen-induced pulmonary platelet embolism reversibly provoked cardiovascular symptoms of shock: hypotension and bradycardia. Impaired gas exchange during platelet accumulation manifested itself in a reversible arterial hypoxaemia and hypercapnia, followed by a weak acidosis. We were able to inhibit ADP-dependent thoracic platelet accumulation by ticlopidine in a dose-related manner as well as collagen-induced thoracic platelet accumulation by acetylsalicylic acid. The results indicate that behaviour of homologous labelled rat platelets in vivo can easily be monitored, thus offering the opportunity to investigate the effects of antiaggregatory drugs on platelets in their natural environment. PMID- 1871722 TI - Upstream thrombus growth impairs downstream thrombogenesis in non-anticoagulated blood: effect of procoagulant artery subendothelium and non-procoagulant collagen. AB - In the present experiments we have investigated the influence of wall shear rate and axial position on platelet and fibrin deposition which results when flowing human non-anticoagulated blood is exposed to either non-procoagulant fibrillar collagen (human type III) or procoagulant subendothelium (rabbit aorta). Platelet adhesion, thrombus volume and fibrin deposition were morphometrically evaluated at axial positions of 1 and 13 mm following perfusions for 5 min at shear rates of 100, 650 and 2,600 s-1. An axially-dependent decrease of platelet adhesion (34 57%, p less than 0.01-0.05) and thrombus volume (57-80%, p less than 0.05) was observed on collagen at all shear rates. On subendothelium, an axially-dependent decrease was observed for platelet adhesion only at 100 s-1 (29%; p less than 0.01) and for thrombus volume at shear rates of 650 s-1 and above (49-58%, p less than 0.01). Deposition of fibrin on subendothelium was axially decreased (16-42%, p less than 0.05) at all shear rates, while no significant axial differences were seen on collagen. However, substantially more fibrin was deposited on the subendothelium (p less than 0.05), and the upstream platelet adhesion and thrombus volume were lower than on collagen (p less than 0.05) at 100 s-1 and 650 s-1. The axially-dependent phenomena on the two surfaces are consistent with the concept of rapid-growing upstream thrombi which deplete the blood layer streaming adjacent ot the surface of platelets, leading to decreased platelet deposition further downstream.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871723 TI - The use of laser-light scattering and controlled shear in platelet aggregometry. AB - Laser-light scattering was used to observe and quantify the dynamics of human blood platelet aggregation in platelet-rich plasma (PRP). Aggregation was performed in a controlled shear environment by placing the PRP in the annular space between a rotating cylindrical rod and a stationary cylindrical tube. The instrument was capable of very sensitive continuous semi-quantitative measurements of chemically-induced microaggregation. As a demonstration of the technique, results are presented for ADP-induced aggregation at doses of 10, 1, and 0.1 microM and collagen-induced aggregation at a dose of 5 micrograms/ml, each at shear rates of 1,000 s-1 and 500 s-1. Extensive aggregation was observed in response to ADP at even the low dose of 0.1 microM, indicating a high sensitivity to microaggregates. The sensitivity of the ultimate size of the ADP induced aggregates to ADP concentration was shear dependent. The formation of microaggregates by collagen stimulation was shown to be almost immediate, as contrasted with a 10-20 s typical lag when observed turbidometrically. Disaggregation was observed with 1 microM ADP, but this was only partial, as contrasted with the complete recovery of transmittance observed in the turbidometric technique. Electronic particle sizing and counting was employed to semiquantitatively verify the aggregate size distributions found from mathematical conversion of the laser-light scattering data. PMID- 1871724 TI - Baboon fibrinogen adsorption and platelet adhesion to polymeric materials. AB - The role of fibrinogen in mediating platelet adhesion to polymers exposed to blood plasma was studied by comparison of the effect of plasma dilution on fibrinogen adsorption and platelet adhesion, and by the use of coagulation factor deficient plasmas. Polyetherurethane substrates were first preadsorbed with dilute plasma, then contacted with washed platelets suspended in a modified, apyrase containing Tyrode's buffer. Platelet adhesion was studied under static conditions in Multiwell dishes, and also under shearing conditions using a parallel plate perfusion chamber. Fibrinogen adsorption and platelet adhesion were measured using 125I radiolabeled baboon fibrinogen and 111In radiolabeled baboon platelets, respectively. Surfaces were characterized by electron spectroscopy for chemical analysis (ESCA). When fibrinogen adsorption to Biomer was measured after 2 h contact with a series of dilute plasma solutions under static conditions, a peak in adsorption was observed from 0.26% plasma, i.e., adsorption was greater from 0.26% plasma than from either more or less dilute plasma. A peak in subsequent platelet adhesion to the plasma preadsorbed surfaces, measured after 2 h static incubation with washed platelets, was also observed but occurred on Biomer preadsorbed with 1.0% plasma. When fibrinogen adsorption was measured after 5 min contact under shearing conditions, the fibrinogen adsorption peak occurred on surfaces that had been exposed to 1.0% plasma. A peak in platelet adhesion to these preadsorbed surfaces, measured after 5 min contact with the platelet suspensions under shearing conditions, was observed on Biomer preadsorbed with 0.1% plasma. Shifts between the positions of the peaks in protein adsorption and platelet adhesion occurred on other polymers tested as well. Platelet adhesion was almost completely inhibited when baboon and human plasmas lacking fibrinogen (i.e., serum, heat defibrinogenated plasma, and congenitally afibrinogenemic plasma) were used. Platelet adhesion was restored to near normal when exogenous fibrinogen was added to fibrinogen deficient plasmas. Adhesion was also inhibited completely when a monoclonal antibody directed against the glycoprotein IIb/IIIa complex was added to the platelet suspension. Platelet adhesion to surfaces preadsorbed to von Willebrand factor deficient plasma was the same as to surfaces preadsorbed with normal plasma. While it appears that surface bound fibrinogen does mediate the initial attachment of platelets to Biomer, the observation that the fibrinogen adsorption and platelet adhesion maxima do not coincide exactly also suggests that the degree of subsequent platelet adhesion is dictated not only by the amount of surface bound fibrinogen but also by its conformation. PMID- 1871725 TI - Inventory of exogenous inhibitors of platelet aggregation. For the Subcommittee on Nomenclature of Exogenous Hemostatic Factors of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. PMID- 1871726 TI - Inventory of exogenous prothrombin activators. For the Subcommittee on Nomenclature of Exogenous Hemostatic Factors of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. PMID- 1871727 TI - Recommendations for the evaluation and treatment of neonatal autoimmune and alloimmune thrombocytopenia. The Working Party on Neonatal Immune Thrombocytopenia of the Neonatal Hemostasis Subcommittee of the Scientific and Standardization Committee of the ISTH. AB - The following recommendations of the Neonatal Hemostasis Subcommittee of the Scientific and Standardization Committee of the ISTH for the management of neonatal immune thrombocytopenia were prepared by the working party on neonatal immune thrombocytopenia. Evaluation, diagnosis, and treatment of the mother and neonate with alloimmune and autoimmune thrombocytopenia are discussed and current recommendations provided. This document is likely to require frequent future revision(s). PMID- 1871728 TI - Monoclonal immunoglobulins in haemophiliac patients with HIV infection. PMID- 1871729 TI - [Longer good life for all--how do we get it?]. PMID- 1871730 TI - [Patients demand personal protection--even in medical journals]. PMID- 1871731 TI - [Should patients with spinal cord damage dive?]. PMID- 1871732 TI - [Reduced ozone layer and skin cancer]. PMID- 1871733 TI - [Risk factors of cardiovascular diseases in Norway--status and development]. PMID- 1871734 TI - [Cardiovascular screenings in Norwegian counties. Background and implementation. Status of risk pattern during the period 1986-90 among persons aged 40-42 years in 14 counties]. AB - Screening for cardiovascular disease risk factors was carried out in 14 of Norway's 19 counties in 1986-1990 as part of a prevention programme. All residents aged 40-42 were invited. The attendance was 73.5% for males and 82.6% for females. A total of 87,761 persons were examined. The screening included determination of serum cholesterol and triglycerides, measurement of blood pressure, height and weight, and filling in a questionnaire. Mean serum cholesterol was 5.90 mmol/l for males and 5.55 mmol/l for females, mean systolic blood pressure 135.3 and 126.1 mm, and prevalence of daily smoking 43.5 and 41.8%. The risk factor levels in the 341 municipalities of the 14 counties are shown cartographically. For both sexes, the highest risk score was found in the northernmost county, the lowest in southern counties. The risk was also relatively high in some rural areas in southern Norway. By geographical area there was a strong correlation between the risk factor levels of the two sexes, and a less consistent but marked correlation between the means for the various risk factors. PMID- 1871735 TI - [Cardiovascular screenings in Norwegian counties. Trends in risk pattern during the period 1985-90 among persons aged 40-42 in 4 counties]. AB - In 1985-90, two screenings for cardiovascular disease risk factors were carried out with an interval of three years in four Norwegian counties. All residents aged 40-42 were invited to both screening rounds, and certain subgroups from the first round were re-invited to the second round. Compared with the score attained by the first generation, the total mean risk score for myocardial infarction achieved by the second generation was 19% lower in males, and 15.5% lower in females. The main cause of this reduction was lower serum cholesterol level. Based on results from the subgroups, the estimated mean risk score for the total male cohort from the first round had decreased by 10% at the rescreening three years later. It is concluded that the results indicate a continued, and perhaps accelerated, decrease in coronary heart disease mortality, as new generations populate the age groups where this disease is more prevalent. The screenings were part of a prevention programme, and it is reasonable to assume that the efforts by the primary health care services contributed to the improvement. PMID- 1871736 TI - [Prevention of cardiovascular diseases in Rissa]. AB - In 1986 the National Health Screening Service conducted cardiovascular risk factor screening of women and men aged 40-42 in Sor-Trondelag county. In one of the municipalities, Rissa, the level of serum cholesterol was high (7.10 mmol/l in men and 6.64 mmol/l in women), as was the total coronary heart disease risk level. The local health authorities launched a health education programme which included population strategy efforts and a high risk intervention programme conducted by the primary health services. Screening of the next generation of women and men aged 40-42 three years later (in 1989) revealed highly significant lower serum cholesterol levels in both sexes (5.83 mmol/l in men and 5.55 mmol/l in women), and significant lower systolic blood pressure in men. Smoking habits had not changed significantly from the first to the second generation. For men, total coronary heart disease risk level was less than one half the level three years earlier. The attendance rate was high, between 80 and 90%, at both examinations. PMID- 1871737 TI - [Cholesterol-lowering effect of oat]. AB - Use of oat-supplement has been advocated to reduce serum cholesterol concentration. In order to study the effect of a daily dietary supplement of oats on lipid levels we performed three controlled clinical trials in healthy Norwegians and patients with hypercholesterolemia. The studies lasted 3-5 weeks, and oats were added to the diet in bread, breakfast cereals, porridge or crispbread. The serum cholesterol concentrations were reduced by 2.5-5% in four of the five groups with an oat-supplemented diet. No effect was found in the group who ate crispbread. Lipid levels remained unchanged in the three control groups. We conclude that oat products have a small but significant cholesterol lowering effect when given as a supplement to the ordinary Norwegian diet. PMID- 1871738 TI - [Life style, sun-bathing and tanning--what about UV-A solariums?]. AB - This article considers the effects of ultraviolet (UV) light from the sun and UV A sun beds on the skin. Sun worshipping and sun therapy has been en vogue for centuries, but in another way than used today. A changing lifestyle has led to an increase of various skin diseases, including skin cancer. Short wave UV-light (UV B) in particular has been blamed for inducing not only erythema and pigmentation but also more chronic skin lesions. Long wave UV-light (UV-A) has been shown to be the cause of similar changes to the skin but the pigmentation is of another quality and affords less protection against the harmful effects of UV-B. A concept of sun reactive skin typing has been created. This is based on self reported responses to an initial exposure to sun as regards tanning ability and erythema reaction. These two factors have certain practical consequences, not only for UV-phototherapy but also for a person's risk of developing skin cancer. Recently, several research groups and dermatologist have discouraged extensive use of UV-A sun beds because of side effects of varying degrees of seriousness. The possible implications of these side effects for the organism are not fully elucidated and may be more profound than known today. The British Photodermatology Group has issued more stringent rules for persons who despite advice to the contrary, still wish to use UV-A sun beds. PMID- 1871739 TI - [Local sunscreening agents--why, when, how and where?]. AB - Sunscreens are used primarily to protect against sunburn. The cosmetic benefits of sunscreens have been widely accepted with the recent indictment of photoaging as a major cause of wrinkles. It is not so well known that sunscreens also protect against the development of carcinomatous processes in the skin. It is important to protect against UV-A as well as against UV-B because UV-A has an additional effect and can also itself initiate cancer. We advocate use of sunscreens with a high sun protection factor. It is of utmost importance to protect children against the deleterious effects of the sun to prevent development of skin cancer later in life. The article includes an overview of the most common active sunfilter compounds. Allergy to these compounds does occur but is rare. Certain textiles provide good but varying protection against the sun. PMID- 1871740 TI - [Neurological decompression sickness]. AB - We have examined 34 divers, mean age 30 years, after treatment for neurological decompression sickness. The initial symptoms often indicated mild sensory or motor involvement. After recompression treatment five of 19 divers with primary affection of the brain had slight hemiparesis or dysphasia. Nine of 14 divers with primary affection of the spinal cord showed signs of spinal cord dysfunction following treatment. Only 16 divers were recompressed within six hours after start of the neurological symptoms. It is concluded that neurological decompression sickness is a serious disorder with a high rate of residual findings. The condition should be treated with prompt recompression, administration of oxygen, and intravenous fluid. PMID- 1871741 TI - [Diving of patients with spinal cord injuries]. AB - Three patients with traumatic spinal cord injuries of a level below Th 5 have been certified as sports divers in Norway, and an increasing number of other paraplegics and tetraplegics have shown an interest for diving. The article reviews possible complications for these patients during diving. It is concluded that diving is not unsuitable for patients with spinal cord injuries, even for tetraplegics, but these persons run greater risk of complications than healthy divers do. However, on the basis of present knowledge, we have prohibited diving to below 20 m, and patients with spinal cord injuries over Th 5 have so far been advised not to dive. All diving must be performed only after comprehensive training and adaptation. PMID- 1871742 TI - [Different arenas--what significance does this have for physiotherapeutic practice?]. AB - What aspects of the patient's body, way of functioning and life situation fall within or outside the physiotherapists' field of inquiry? This is one of the main questions in a research project to analyse first encounters in physiotherapy practice, based on videotapes of the encounters and semi-structured interviews. The article focuses on the relation between the examination approach, communication, and the setting of the encounters. Data from two of the videotaped encounters are used as a basis for a more general presentation and discussion. One of the findings was that the setting of the encounters influenced the professional's attention in some way or other, and had a significant effect on the information acquired and on the relationship that developed between the two parties. It appears that the orientation and real practice of a professional need to be interpreted in the context of institutional and external factors and of the ongoing interaction developed in the situation. PMID- 1871743 TI - [Ratfish (chimaera monstrosa) sting]. AB - A fisherman was accidentally stung on his right calf by the spine of a ratfish (chimaera monstrosa). Adjacent to the wound was a swelling, with a bluish skin colour the first day. The fisherman experienced an immediate burning pain and during the following days developed numbness of the calf and the back of the thigh. He needed crutches for three weeks, and the symptoms lasted for nine weeks. The treatment consists of rinsing the wound and removing foreign material, and submerging the afflicted limb as soon as possible in water as hot as the patient can tolerate for at least 30 minutes. PMID- 1871744 TI - [Carl Robert Henie (1850-1919) and his survey of school children's teeth in 1897. A pioneer work in Norway]. AB - At the end of the 19th century dental caries had become a serious health problem in many countries, especially among children and young people. Filling their teeth was not common practice among ordinary people. Extraction was usually the only treatment offered. Surveys of schoolchildren's teeth were carried out in many countries in order to establish the extent of the problem, to find out some of the causes, and to stop rotting of teeth. In Norway, the doctor Carl Robert Henie (1850-1919) carried out such a survey in the mid-1890s at Hamar. He examined 660 children (347 boys and 313 girls) aged 7-17 years. Unfortunately he does not say how the examination was carried out, whether he had a good light for his work, or whether or not he used instruments. It is reasonable to assume that he examined the children's teeth in ordinary day-light without using a probe. In this case, many incidents of caries would have been overlooked, leading to no small degree of underreporting. This means that his results cannot be compared out of hand with more recent registrations. Henie, like many others of his contemporaries, maintained that dental caries is a disease of civilization, and emphasized a proper diet containing less refined and processed foods. He recommended coarse bread made from whole-meal flour. He also emphasized the use of fluorine and calcium to prevent caries. His efforts helped to draw the attention of the authorities to a neglected area of health work, and to the establishment of the first school dental clinics in the country a few years later. PMID- 1871745 TI - [Dentistry in developing countries]. AB - The author presents different approaches to dental activities in developing countries. The general prevalence of dental caries and periodontitis in developing countries is low. The limited resources for health programmes, and for oral health in particular, underscore the need to make priorities in order to improve the health of the inhabitants. To promote oral health, it is necessary to focus on improving knowledge about the major oral diseases and the possibility of developing community-based programmes of intervention and prevention. The integration of oral health into general health programmes is a major goal in the prevention and combat of oral diseases. Knowledge and research in fields of oral medicine, preventive oral programmes as well as in fluoride toxicology as part of water programmes is important. PMID- 1871746 TI - [Assistance work in Romania. A multidisciplinary study of institutionalized children]. AB - In October/November 1990 a health team worked in an institution for mentally retarded children in Rumania. The team diagnosed 154 children and encountered children with undernourishment, retarded growth, skin infections, injuries and untreated physical deformities. 11 children were in need of acute medical attention. Cerebral palsy and motoric, auditive and visual handicaps were not attended to. The children showed signs of deprivation, anxiety and behavioural maladjustment. They were mentally retarded, but receptive to stimulation. To conclude, the children suffered from physical, psychological, pedagogic and social neglect. The article provides information on the needs for further assistance to children in institutions in Rumania. PMID- 1871747 TI - [Diagnosis of malabsorption]. PMID- 1871749 TI - [Between mother and child--early fetal diagnosis as a routine in antenatal care]. AB - The development of high-resolution real-time ultrasound has created the opportunity to identify fetal congenital anomalies. Making this technique part of a screening activity must be based on the belief that early identification and early care will have a favourable impact on the natural history of the disease. This is not the case when pregnancies are screened in the second trimester to detect malformations. On the contrary; in Norway, this might lead to the yearly elimination of 300 desired fetuses. Some of these would otherwise have had a longer intrauterine life, some might have benefited from postnatal medical treatment and some might otherwise have been born as healthy children instead of being eliminated due to misclassification. PMID- 1871748 TI - [Anesthetic gases, the ozone layer and the greenhouse effect. How harmful are the anesthetic emissions for the global environment?]. AB - During the last decade, world society has acknowledged the harmful effects on the environment of the greenhouse effect and of depletion of the ozone layer, caused by industrial emissions of man-made compounds. Ozone depletion is caused mainly by chlorine compounds or nitrogen oxides released by degradation in the stratosphere. The greenhouse effect is caused by increased trapping of terrestrial heat radiation. Degradation of the anaesthetic vapours halothane, enflurane and isoflurane releases chlorine, and nitrous oxide degradation produces reactive nitrogen oxides. Nitrous oxide in particular, but also the vapours, absorb terrestrial radiation. The total discharge of anaesthetic vapours contributes to less than 0.01% of the total atmospheric chlorine load, and the annual Norwegian release of approximately two tons accounts for 0.2% of the world total. It is estimated that the total amount of nitrous oxide released from anaesthetics accounts for 0.05% of the greenhouse effect, while annual Norwegian emissions of nitrous oxide (less than 160 tons) comprise 0.2-0.4% of world total. Because of their favourable clinical properties and their modest contribution to ozone depletion and the greenhouse effect, medical use of inhalational anaesthetic agents should not be banned. However, low flow anaesthetic techniques should be employed, in order to reduce their negative impacts on the atmosphere. PMID- 1871750 TI - [Infant nutrition in Norway in the light of recent research]. AB - Broadly speaking, infant nutrition in Norway is good during the first six months. Fortunately breast feeding is very common. In the second half of the first year, however, our infant nutrition is not quite in accord with recent research. The iron intake is less than recommended, and in many infants the iron status at one year of age is not satisfactory, although serious degrees of iron deficiency anemia are rare. Many infants are given cow's milk from six months of age, and thus receive more protein and electrolytes than desirable. This represents an unnecessary load on metabolism, fluid balance and kidneys, with too high "potential renal solute load". Insulin secretion is stimulated to a higher degree than with breast milk, and there is also some blood loss in the stools. The author emphasizes the importance of essential unsaturated fatty acids, particularly the fatty acids in marine oils (cod liver oil), and proposes a simple and inexpensive adjustment of Norwegian infant nutrition. PMID- 1871751 TI - [The prestige of diseases and medical specialties]. AB - Diseases and medical specialties differ as regards social prestige. Samples of experienced physicians, medical students at two different levels, and other health professions were asked to rate 38 diseases and 22 medical specialties and subspecialties by prestige. The measured differences in prestige were substantial. Among the diseases, myocardial infarction, leukemia and brain tumour were ranked highest, whereas fibrositis, hepatocirrhosis and depressive neurosis came lowest. Among the specialties, neurosurgery, cardiology and thorax surgery were top ranked, while geriatrics, dermatology and psychiatry had lowest prestige. The differences between the ratings of the doctors, medical students and representatives of other health professions were small. This result indicates that the resulting scales of prestige of diseases and specialties, besides being of interest in themselves, can be used for purposes of analysis, e.g. in analysis of the allocation of economic resources in the health services. PMID- 1871752 TI - [The physician's choice of a specialty]. AB - This study included 1,416 graduates from the four medical schools in Norway, during the period 1978-81. The purpose was to determine which factors potentially influence choice of specialty. There were some differences in choice of specialty between physicians from different universities. Choice of specialty also varied with sex, age, and examination performance. Female physicians took no more time than their male colleagues did to become specialists. It is also concluded that the quality of the undergraduate teaching of the different specialties had little or no impact on future choice of career. PMID- 1871754 TI - [Responsibility and care]. PMID- 1871753 TI - [Small hospitals--future tasks and functions]. AB - We review the small municipal hospitals included in our study of hospitals serving less than 50,000 persons. We identified the following problems: These hospitals are resource-intensive to a greater degree than expected, measured in terms of beds, doctors, health services and per capita costs in the area served by the hospital. Moreover, their quality is questionable, due to problems of recruitment and lack of continuity, a weak infrastructure, and insufficient patients to maintain a high level of competence, especially in taking care of patients with complicated and acute conditions. We foresee, and recommend, a new and different future for small hospitals, emphasizing closer links with primary health care and closer collaboration with the larger county hospitals. Key words are: Outpatient services, including perhaps ambulatory specialist services from the larger hospitals, elective services in fields of special competence, possibly covering a larger area, rehabilitation services, municipal psychiatric services; and finally, the traditional acute services should be changed to a first-aid service, preferably as part of emergency care in the municipality. PMID- 1871755 TI - [Prevention of myocardial infarction by reducing serum cholesterol levels. High risk strategies should be limited]. AB - Prevention of premature myocardial infarction is an important public health issue. Two different approaches may be used in order to prevent premature myocardial infarction, a high-risk strategy and a population strategy. The report discusses prevention of myocardial infarction in middle-aged Norwegian individuals by reducing total serum cholesterol and using the high risk and population strategies. A combination of these strategies is recommended, but with major emphasis on the population approach. Both trials and calculations indicate that the high-risk strategy should be limited to subjects with very high serum cholesterol (e.g. greater than or equal to 8 mmol/l in middle-aged men). PMID- 1871756 TI - [Nutrition or industry. Experiences with nutritional considerations in the agricultural policy]. AB - The need to export health considerations to various sector policies is regarded as important in health promotion. Health is generally a highly appreciated benefit; thus many sectors seek to use health as an argument for their policy. This article describes the relation between nutrition and agricultural policy in Norway. In areas where nutrition and agriculture had mutual interests, health considerations were easily exported. However, when interests diverged the issue became more complicated. Much effort was focused upon achieving correct use of nutritional arguments. Before negotiating and weighing respective viewpoints it is essential to clarify each sector's standpoint and interest. Conflicts and negotiations are linked to strategies which seek explicitly to integrate health premisses into sectors outside the health services itself. PMID- 1871757 TI - [Small hospitals--future tasks and functions]. PMID- 1871758 TI - [Smoke free environment]. PMID- 1871759 TI - [Cancer among captains and mates on the Norwegian tankers]. PMID- 1871760 TI - [Sterile water papulae give analgesia during labor]. PMID- 1871761 TI - [The snake in the light of medical and religious history--medical and pharmaceutical symbols]. PMID- 1871762 TI - [The spectre of dependence. Health hazards of snuff use]. PMID- 1871763 TI - Production and characterization of human monoclonal lymphocytotoxic autoantibodies from a renal dialysis patient. AB - We have produced human monoclonal lymphocytotoxic autoantibodies from a renal dialysis patient by the generation of a mouse/human heterohybridoma. The antibodies are of the IgM class and react with the patient's autologous cells, the B-lymphoblastoid cell line producing the antibody, normal T and B lymphocytes, B cells from chronic lymphatic leukemia patients (CLL cells), and the autoantibody-sensitive cell line K562. Screening of the monoclonal antibodies (mAb) against panels of normal T and B cells and CLL cells demonstrated that different reactivity profiles could be generated at different dilutions of the mAb. These profiles were identical to those seen with autoantibodies from different renal patients and this suggests that these profiles do not imply different antibody specificities but differing target cell sensitivity. Reactivity profiles seen in the fluorescence binding assays suggest that the target cell sensitivity is dictated not by antigen density alone but also by antibody/antigen affinity. The results from studies of enzyme treatment of target cells and lectin inhibition of the molecular specificity suggest that the autoantibodies are polyreactive, capable of binding sialic acid-dependent epitopes and other negatively-charged cell surface molecules. PMID- 1871764 TI - The HLA-DQ beta non-Asp-57 allele: a predictor of future insulin-dependent diabetes mellitus in patients with autoimmune Addison's disease. AB - HLA-DR specificities in 72 Addison's (AD) patients and 808 local controls were compared. We confirmed earlier reports that the HLA-DR3 specificity is significantly increased in AD patients. In our study a relative risk of 3.4 chi 2 = 22.5; pc = 0.01) for the disease was calculated. Analysis of HLA-DQB1 alleles in DR4+ Addison's patients with diabetes mellitus (N = 6) and without IDDM (14 of 18 individuals tested) revealed that the HLA-DQw8 allele (DQB1*0302) was significantly increased in AD patients with IDDM (chi 2 = 13.5; p = 0.001); conversely, a clustering of the HLA-DQw7 allele was detected in DR4+ Addison's patients without IDDM. We thus conclude that particular polymorphic alleles corresponding to non-charged amino acids at position 57 of the HLA-DQ beta-chain [non-Asp-57 alleles] are associated with IDDM also in Addison's patients. PMID- 1871765 TI - The two major subtypes of HLA-B44 differ for a single amino acid in codon 156. PMID- 1871766 TI - Activated human T cells express beta 2-microglobulin-associated HLA-A,B,C molecules not recognized by W6/32 mAb. PMID- 1871767 TI - HLA (A, B, C and D) antigens in the Awa-Kwaiker Indians of Colombia. PMID- 1871768 TI - Toxicokinetics of permethrin in the rat. AB - The toxicokinetics of permethrin after single 460 mg/kg oral and 46 mg/kg intravenous doses were studied in male Sprague-Dawley rats. Serial blood samples after oral and intravenous dosage, and brain, medulla oblongata, sciatic nerve, and liver samples after oral administration were collected. Plasma, hypothalamus, cerebellum, frontal cortex, caudate putamen, hippocampus, medulla oblongata, sciatic nerve, and liver concentrations of permethrin and its metabolites, m phenoxybenzyl alcohol and m-phenoxybenzoic acid, were determined by a high performance liquid chromatographic assay. The permethrin plasma profile could be adequately described by a two-compartment open model. For permethrin, the elimination half-life (t1/2 beta) and the mean residence time from plasma were 8.67 and 11.19 hr after i.v. and 12.37 and 17.77 hr after po administration. The total plasma clearance was not influenced by dose concentration or route and reached a value of 0.058 liter/hr. After the single oral dose, permethrin was absorbed slowly with a Tmax of 3.52 hr. The maximum plasma concentration was 49.46 micrograms/ml. The oral bioavailability of permethrin was found to be 60.69%. The plasma concentration-time data for permethrin metabolites as well as the tissue concentration-time data for permethrin and its metabolites after an oral dose of permethrin were found to fit a one-compartment open model. The elimination half-life (t1/2el) of permethrin was greater for the hippocampus, medulla oblongata, frontal cortex, and sciatic nerve (23.10, 22.36, 13.86, and 16.27 hr, respectively) than for plasma (t1/2 beta, 12.37 hr). The maximum amounts of permethrin in cerebellum, hippocampus, caudate putamen, frontal cortex, hypothalamus, and sciatic nerve were about 1.5, 2, 2, 2.7, 4.8, and 7.5 times higher than in plasma, respectively, indicating an accumulation of pyrethroid by nervous tissue itself. Nervous tissue accumulation of permethrin was also reflected by the area under the concentration curve ratios of tissue/plasma (1.16, 3.71, 1.57, 4.27, 3.48, and 8.77, respectively). The metabolites of permethrin, m-phenoxy-benzyl alcohol and m-phenoxybenzoic acid, were detected in plasma and in all selected tissues for 48 hr after dosing, suggesting that a combination of metabolism by the tissues and diffusion into it from the blood may be present. PMID- 1871769 TI - Splenic cell targets in gallium arsenide-induced suppression of the primary antibody response. AB - In vivo exposure of female B6C3F1 mice to gallium arsenide (GaAs) was evaluated for its effect on the in vitro IgM antibody-forming cell (AFC) response. In vivo exposure to a single intratracheal dose of GaAs (2.5-200 mg/kg) resulted in a dose-dependent decrease in the in vitro IgM AFC response to the T-dependent antigen sheep red blood cells (SRBC) with a 97% decrease at 200 mg/kg when compared to vehicle controls. The response to the T-independent antigen DNP Ficoll was significantly reduced at 100 and 200 mg/kg. Spleen cellularity decreased in a dose-related manner with a 54% decrease at 200 mg/kg. Enumeration of splenic subpopulations following GaAs (200 mg/kg) indicated a 58, 61, and 30% decrease in the total number of Thy 1.2 (T cells), Ig (B cells), and F4/80 (macrophages) positive cells, respectively, with no alterations in the percentages of these cells. Mitogenic responsiveness of splenocytes from GaAs exposed mice was unaltered. To identify the splenic cell populations targeted by GaAs, the AFC response to SRBC was evaluated following cell separation/reconstitution of splenocytes from GaAs- (200 mg/kg, 24-hr exposure) and vehicle-exposed mice. Results demonstrated AFC suppression was due to functional alterations in both adherent (AD; macrophages) and nonadherent, (both T and B lymphocytes) cell populations. Further investigation focused on alterations in the AD population. Separation/reconstitution experiments demonstrated AFC suppression to SRBC was dependent on the concentration of macrophages from GaAs-exposed mice. This macrophage-mediated suppression of the in vitro AFC response could not be attributed to the presence of suppressor macrophages or release of prostaglandins. PMID- 1871770 TI - Promotion of organophosphate-induced delayed polyneuropathy by phenylmethanesulfonyl fluoride. PMID- 1871771 TI - Effect of hepatotoxic chemicals and hypoxia on hepatic nonparenchymal cells: impairment of phagocytosis by Kupffer cells and disruption of the endothelium in rat livers perfused with colloidal carbon. AB - Kupffer cells play an important role in liver function and phagocytosis of foreign particles in the hepatic portal tract. Therefore, the purpose of this study was to investigate the influence of several hepatotoxic chemicals (allyl alcohol, ethylhexanol, and menadione) and hypoxia on phagocytic activity of Kupffer cells in perfused rat liver. A recently developed optical method was used to determine rates of phagocytosis of carbon particles by Kupffer cells in periportal and pericentral regions of the liver lobule based on changes in reflected light from the liver surface (te Koppele, J.M., and Thurman, R.G. 1990. Am. J. Physiol. 259, G814-G821). With all chemicals studied, a rapid (10-30 min) decline in the rate of phagocytosis preceded parenchymal cell death as assessed from release of lactate dehydrogenase. These chemicals impaired parenchymal cell energy status as indicated by inhibition of O2 uptake and bile flow prior to cell death. Livers swell when they are damaged, a process which increases perfusion pressure and could theoretically damage the endothelium and lead to nonspecific uptake of carbon. In perfusions with a hepatotoxic concentration of allyl alcohol (350 microM), carbon particles accumulated in swollen livers after 70 min of perfusion. Histological studies revealed that carbon particles were localized predominantly in periportal regions of the liver lobule in perfusions with all hepatotoxicants studied. When perfusion pressure was elevated to 20 cm H2O in the absence of hepatotoxicants, carbon particles detected optically accumulated in upstream regions of the liver lobule (periportal or pericentral regions in perfusions in the anterograde or retrograde directions, respectively). In scanning electron microscopy of nonswollen livers, the endothelium remained intact. In swollen livers, however, the endothelium was disrupted and carbon was detected bound nonspecifically to parenchymal cells. Fifteen minutes after addition of allyl alcohol, bile canaliculi were dilated and endothelial fenestrations were enlarged. After 2 hr of perfusion with allyl alcohol, hepatic ultrastructure was severely disrupted. Thus, it is concluded that perfusion with hepatotoxic chemicals or hypoxia results in a rapid decrease of particle phagocytosis by Kupffer cells followed by changes in endothelial cell ultrastructure. PMID- 1871772 TI - The urotoxic effects of N,N'-dimethylaminopropionitrile. 2. In vivo and in vitro metabolism. AB - The urotoxicity and metabolism of N,N'-dimethylaminopropionitrile (DMAPN) were investigated in male Sprague-Dawley rats. Animals treated with 525 mg DMAPN/kg or equimolar doses of commercially available potential DMAPN metabolites showed varying levels of urinary retention. About 44% of the administered dose of DMAPN was excreted unchanged in 5 days. beta-Aminopropionitrile and cyanoacetic acid were identified as urinary metabolites. The urinary excretion of cyanoacetic acid was nonlinearly proportional to the volume of urine retained in the bladders. In vitro, the metabolism of DMAPN to cyanide, formaldehyde, and cyanoacetic acid was localized mostly in the microsomal fraction of liver, kidney, and urinary bladders. This reaction required NADPH and oxygen for maximal activity. Metabolism of DMAPN was increased in hepatic microsomes obtained from phenobarbital-treated rats (220% of control) and decreased following CoCl1 treatments (73% of controls). Addition of SKF 525-A to the incubation mixtures inhibited the metabolism of DMAPN to formaldehyde (47-64% of controls). Addition of sulfhydryl compounds (glutathione and cysteine) to the incubation mixtures did not affect the rate of these reactions. These findings indicate that DMAPN is primarily metabolized via a cytochrome P450-dependent mixed-function oxidase system and that the urotoxic effects of DMAPN may be related to this metabolism. PMID- 1871773 TI - Role of metabolites in propanil-induced hemolytic anemia. AB - Hemolytic anemia and methemoglobinemia induced by exposure to certain arylamines, such as aniline and dapsone, are known to be mediated by their N-hydroxylamine metabolites. The arylamide propanil (3,4-dichloropropionanilide), a herbicide used extensively in rice fields, is also thought to induce methemoglobinemia through the action of metabolites. However, the hemolytic potential of this compound has not previously been reported. The present studies were undertaken to determine the hemolytic potential of propanil, and, if positive, the role of metabolites in this hemotoxicity. The survival of previously administered 51Cr labeled erythrocytes in rats was reduced in a dose-dependent manner by ip administration of both propanil and its deacylated metabolite, 3,4 dichloroaniline (ED50 for both ca. 1.8 mmol/kg). When labeled erythrocytes were exposed in vitro to propanil or 3,4-dichloroaniline and then readministered to rats, no decrease in erythrocyte survival was observed, which indicated that these compounds were not direct-acting hemolytic agents. In contrast, erythrocyte survival was markedly reduced by ip administration or in vitro exposure to N hydroxy-3,4-dichloroaniline. In addition, N-hydroxy-3,4-dichloroaniline was detected in the blood of propanil-treated rats in amounts sufficient to account for the hemolytic activity of the parent compound. These data indicate that N hydroxy-3,4-dichloroaniline mediates propanil-induced hemolytic anemia, and that occupational exposure to propanil may result in an increased risk of hemolytic episodes. PMID- 1871774 TI - Comparison of three physiologically based pharmacokinetic models of benzene disposition. AB - We assess the goodness of fit of three physiologically based models of benzene pharmacokinetics to experimental data in Fischer-344 rats. These models were independently developed and published. Large differences in the quality of the fit are observed. In addition, the parameter values leading to acceptable fits are spread over the entire range of physiologically plausible values and can be quite different from average or standard values. On the other hand, choosing standard values for the parameters does not ensure good predictions of all tissue levels. These results emphasize the difficulty of a rigorous calibration of physiological models, and the need for further research in this area, including precise experimental determination of parameter values. Physiological models are powerful tools, but for risk assessment purposes simpler models, making equivalent use of the crucial data, are probably preferable. PMID- 1871775 TI - Copper-induced toxicity in macular mutant mouse: an animal model for Menkes' kinky-hair disease. AB - These studies were designed to determine if macular mutant mouse, which is a proposed animal model of Menkes' kinky-hair disease, is sensitive to the acute toxic effect of Cu as compared to normal and heterozygote mice. Single sc injection of Cu were administered to 6- to 8-day-old mice, and mortalities were recorded for 30 days. The copper treatment at high doses (12 to 25 mg Cu/kg) was very toxic to mutant mice as compared to normal mice, and almost all mutant mice died within 10 days after injection. The effect of Cu toxicity on heterozygote mice was intermediate. The LD50 values 3 days after injection of Cu were 29.5 mg Cu/kg for normal mice, 23.5 mg Cu/kg for heterozygote mice, and 15.5 mg Cu/kg for mutant mice. In Cu-injected mutant mice (11 and 18 mg Cu/kg), significant elevations in serum aspartate aminotransferase and lactate dehydrogenase activity occurred as compared to Cu-injected normal and heterozygote mice. However, no significant elevations in serum creatinine and urea nitrogen contents in Cu injected mutant were observed as compared to normal and heterozygote mouse. No significant differences in hepatic metallothionein(MT) and MT-1 mRNA, and serum ceruloplasmin oxidase activity levels were observed between Cu-injected normal and mutant mouse. These results indicated that macular mutant mice was sensitive to the acute toxic or hepatotoxic effects of Cu as compared to normal and heterozygote mice. PMID- 1871776 TI - Inhibitory effect of rhodamine B on the proliferation of human lip fibroblasts in culture. AB - The effect of the cosmetic dye rhodamine B on the proliferation of human lip fibroblasts (KD cells) was investigated in a culture system. Rhodamine B at 25 micrograms/ml and above significantly decreased the number of the cells after a 72 h culture. A time course study revealed that 50 micrograms/ml of rhodamine B induced decrease in the cell number occurred after 48 h and longer, suggesting that the dye inhibited cell proliferation without a decrease in cell attachment. The detachment of [3H]thymidine-labeled cells from the monolayer was unaffected by rhodamine B at 100 micrograms/ml and below. The incorporation of [3H]thymidine and [14C]leucine into the acid-insoluble fraction of the cell layer was significantly inhibited by 50 micrograms/ml rhodamine B treatment. Histologically, the damage of KD cells was not marked, however, a degenerative change of nuclei and an irregular shape of the cells as well as a decrease in the cell number were caused by 50 micrograms/ml rhodamine B. Rhodamine 6G caused a severe damage of the cells, and rhodamine B significantly decreased the cell number; rhodamine 123 had no significant effect; rhodamine 116 significantly increased the cell number. Furthermore, rhodamine B decreased the number of both vascular endothelial cells from bovine aorta and vascular smooth muscle cells from murine aorta after a 72 h culture. It is concluded that rhodamine B inhibits the proliferation of human lip fibroblasts. This rhodamine B effect may be a warning sign for the dye toxicity. PMID- 1871777 TI - Preclinical toxicity studies of an adenosine agonist, N-(2,2-diphenylethyl) adenosine. AB - N-(2,2-Diphenylethyl)adenosine (DPEA) has been identified as a potential antipsychotic agent acting via stimulation of adenosine receptors. The projected human therapeutic dose, based on animal studies, is 2-3 mg/kg. DPEA has been tested for potential toxicity in mice, rats, dogs and monkeys. Following single oral doses, median lethal dose values were approximately 10-fold greater in rats than in mice, although similar clinical signs including reduced activity, prostration, and necrosis of the tail were seen in both species. DPEA was well tolerated at daily doses up to 40 mg/kg in rats for 2 weeks. A no observed effect level (NOEL) was not identified in the dog or monkey studies. Reduced activity, dacryorrhea, ptosis, hypothermia, necrosis of the tail, and death occurred in rats given 120 and 160 mg/kg. Pathologic changes consisted of pancreatitis, gastric erosion/ulceration, lymphocyte depletion of the thymus, and pulmonary congestion and hemorrhage at 80 mg/kg or greater. In dogs, sporadic emesis was noted at 12.5 mg/kg and greater, and significant pathologic changes consisted of coronary arteritis associated with myocardial lesions and lymphocyte depletion at 25 and 50 mg/kg, pancreatic acinar necrosis at 50 mg/kg, and renal tubular degeneration at 12.5 mg/kg and greater. Emesis and depression were noted at 25 and 50 mg/kg in monkeys. Renal tubular dilatation and degeneration at 25 and 50 mg/kg were noted in the monkeys. These studies demonstrated that DPEA produced a range of adverse effects in common laboratory animal species. PMID- 1871778 TI - The effect of toluene on rat lung benzo[a]pyrene metabolism and microsomal membrane lipids. AB - Toluene (1 g/kg, i.p., 1 and 4 h) was shown to decrease total cytochrome P-450 (P450) content in rat lung. At both timepoints, reduction in pulmonary P450 content was associated with a decrease in aryl hydrocarbon hydroxylase (AHH) activity, a detoxication pathway for benzo[a]pyrene (BaP). At 4 h, toluene increased the toxication/detoxication ratios of BaP metabolites in pulmonary microsomes, primarily via inhibition of hydroxy metabolite formation. The structurally analogous solvents p- and m-xylene have been previously shown to produce a similar pattern of MFO changes in rat lung; the inhibition of BaP metabolism was found to be related to alterations in pulmonary microsomal lipids following administration of p- but not m-xylene. In the present study, toluene induced alterations in MFO parameters were not found to be associated with changes in microsomal lipids. Toluene did not affect either total phospholipid or cholesterol content at either timepoint. Similarly, no changes in speciated phospholipids were observed. Membrane integrity, expressed as conjugated diene formation, also remained unchanged following toluene administration. Toluene did, however, decrease microsomal inner-core membrane fluidity at 4 h but had no effect on membrane leaflet fluidity at either timepoint. These data suggest that the fatty acid composition of microsomal lipids may play a role in the metabolic alterations observed in pulmonary microsomes following toluene administration. PMID- 1871779 TI - Influence of aromatic hydrocarbons on the metabolism of dichloromethane to carbon monoxide in rats. AB - The influence of prior or simultaneous oral administration of benzene, toluene, o , m-, or p-xylene on the carboxyhemoglobin (COHb) level after a single dose of dichloromethane (DCM) was investigated in male rats. Six hours after administration of DCM, 6.2 mmol/kg, the mean maximum COHb level was 9.3 +/- 1.9%. This level was significantly enhanced by prior administration of benzene (16.9 mmol/kg) at 12-24 h, of toluene (18.8 mmol/kg) at 20-28 h, of o- (16.6 mmol/kg) and m-xylene (16.3 mmol/kg) at 20-32 h, and of p-xylene (16.2 mmol/kg) at 24-32 h. The corresponding maximum COHb levels were 20.7 +/- 1.3, 18.6 +/- 1.1, 18.9 +/ 1.1, 22.7 +/- 1.2, and 13.2 +/- 1.0%, respectively. After simultaneous administration of both DCM and the aromatic solvent, the COHb formation was inhibited: values of 1.3 +/- 0.3, 1.7 +/- 0.4, 3.6 +/- 0.2, 1.9 +/- 0.2, and 2.0 +/- 0.2% COHb, respectively, were found. The inhibition was also evident when DCM was administered 12 h after toluene or m-xylene and 12, 16 or 20 h after p xylene. The inhibition was dose-related as seen after combined gavage of o-, m-, or p-xylene and DCM. The o- and m-, but not the p-methylhippuric acid (MHA) excretion in the urine was significantly reduced after simultaneous administration of equimolar doses of DCM and the corresponding xylenes. In conclusion, it seems that the stimulation or inhibition of the COHb formation after DCM caused by pretreatment with or by simultaneous administration of the aromatic solvents is due to the induction of cytochrome P-450 IIE1 or to competition between DCM and the aromatic solvent on this isozyme of cytochrome P 450. PMID- 1871780 TI - Carbon-13 nuclear magnetic resonance spectral data of steroidal vicinal ketols and related compounds. AB - Carbon-13 nuclear magnetic resonance spectra for 31 3 beta-hydroxy and acetoxy androstane derivatives bearing vicinal oxygenated functions at ring D with and without oxygenated functions at C-6 are reported. Relative substituent effects are discussed. PMID- 1871781 TI - Synthesis and mechanism of hydrolysis of estrogen 6-sulfates: model compounds for demonstrating the carcinogenesis of estrogen. AB - To investigate the carcinogenesis of estrogen with respect to the chemical behavior of estrogen 6-sulfates, two epimeric 6-sulfates, pyridinium 3 methoxyestra-1,3,5(10)-trien-6 alpha-yl (8) and -6 beta-yl (11) sulfates, were synthesized as the model compounds, and their chemical reactivities were examined. These sulfates were shown to be highly reactive: in water, they were readily and quantitatively converted to a common product mixture, composed of 3 methoxyestra-1,3,5(10)-trien-6 alpha-ol (6) and -6 beta-ol (9) in an almost constant product ratio, with a predominant yield of the latter. The hydrolysis of both sulfates 8 and 11 proceeded in first-order kinetics with half-lives of 1.1 and 1.5 minutes, respectively. When the sulfates were hydrolyzed in 18O-water, the heavy-oxygen atom was shown to be incorporated quantitatively into the C-6 position of the products. These results demonstrate that estrogen 6-sulfates generate a highly reactive benzylic (C-6) carbocation in an aqueous solution, suggesting that the sulfates can act as carcinogens. PMID- 1871782 TI - Regioselectivity of metabolic activation of acetylenic steroids by hepatic cytochrome P450 isozymes. AB - Liver cytochrome P450 monooxygenases (P450), a group of isozymes that catalyze the reductive cleavage of molecular oxygen, dominate hepatic metabolism of xenobiotic lipophilic substances. These P450 enzymes exhibit broad and overlapping substrate specificities, in contrast to the P450 isozymes of the steroid biosynthetic pathways, which are highly substrate specific. Hepatic heme pigments, N-alkylated porphyrins, accumulate following the self-catalyzed destruction of P450 by the metabolic activation of 17 alpha-ethynyl steroids. Acetylenic substituted steroidal aromatase inactivators, norethisterone (NET), and 10-(2-propynyl)estr-4-ene-3,17-dione (MDL 18,962) were administered to rats to determine if the acetylenic substituent was activated by hepatic P450 mixed function oxidases. This metabolism could result in the formation of a reactive species that would alkylate a pyrrole nitrogen atom of heme. Male Sprague-Dawley rats were treated with 0, 10, 30, or 100 mg/kg NET or MDL 18,962 intraperitoneally. Four hours later, these animals received 40 mg/kg sodium pentobarbital and their sleeping times were recorded. On arousal, the rats were killed and their livers were taken for determination of P450 content and formation of N-alkylated porphyrins (green pigments). Norethisterone inhibited hepatic P450 isozymes, resulting in a dose-related increased sleeping time (89.2 +/- 3.5 to 156.3 +/- 7.6 minutes) and decreased P450 levels (maximum 25% decrease at 100 mg/kg), and the amount of green pigments increased with doses of 10 to 100 mg/kg. In contrast, MDL 18,962 treatment did not increase sleeping time and caused only a 15% decrease in hepatic P450 content at 100 mg/kg, with no detectable green pigments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1871783 TI - New steroid haptens for radioimmunoassay: synthesis of steroids substituted with thioether or ester linkages at the 2 alpha-position. AB - Haptens with bridge at the 2-position have not yet been explored. Radioimmunoassays with antibodies directed against 2 alpha-alkyl bridged steroid haptens are expected to be highly specific due to greater topographical exposure and similarity in conformation to the native steroid. The 2 alpha-alkyl bridged haptens were synthesized by first adding a cyclopropane ring to 2-methylene-4-en 3-one. Selective opening of the three-membered ring with trimethyl silyl iodide and transformation of the iodo group gave a carbocyclic acid, the desired analog for conjugation with protein. PMID- 1871784 TI - Regioselective reactions of 1,2-dehydroprogesterone: syntheses of pregnane derivatives as possible contragestational agents. AB - A few pregnane derivatives were synthesized from 1,2-dehydroprogesterone (1). Ring A of 1,2-dehydroprogesterone was aromatized without affecting C-20, and the resulting acetoxy compound (2) after hydrolysis yielded 1-hydroxy-4-methyl-19 norpregna-1,3,5(10)-trien-20-one (3). Reactions of the phenol (3) with alkyl halides yielded the ethers 6a-6b and 7. Opening of the oxirane ring in 7 with secondary amines furnished the aminoalcohols 8a-8b. Friedelcraft's reaction of 3 with maleic anhydride and chloracetyl chloride led to the formation of 9 and 10, respectively. Base-catalyzed ring closure of 10 yielded 1-acetyl-12a-methyl-8-oxo 5[H]-1,2,3,3a,3b,4,8,9,10b,11,12, 12a-dodecahydrocyclopenta (7,8)-phenanthro (3,4 b) furan (11), which reacted with aromatic aldehydes regioselectively to furnish 12a-12b. Reaction of 1 with triethylorthoformate in the presence of boron trifluoride etherate involved the participation of C-21, and the carbonyl at C-3 remained unaffected. The product 13 was identified as 21-[2-hydroxyvinyl]-21 norpregna-1,4-diene-3,20-dione. Reductive amination with sodium cyanoborohydride in the presence of ammonium acetate did not attack ring A and smoothly furnished the amine 14 which, on reaction with succinic anhydride, gave 20-succinamylpregna 1,4-dien-3-one (15). PMID- 1871785 TI - Omega 1-decoupled 1H homonuclear shift-correlated nuclear magnetic resonance spectroscopy (COSYDEC) applied to steroids. AB - Problems of cross-peak overlap in two-dimensional 1H homonuclear shift-correlated (COSY) spectra of steroids can often be avoided by use of the omega 1-decoupled COSY (COSYDEC) method. The selection of experimental parameters is discussed, and COSYDEC spectra are illustrated for 17a-oxa-D-homoandrost-4-ene-3,17-dione (testololactone), testosterone, and 17 alpha-hydroxyprogesterone. In a good case, a COSYDEC spectrum obtained at 250 MHz allows cross-peak recognition and assignment with facility comparable to that available only at 500 MHz for normal COSY spectra. PMID- 1871786 TI - Interaction of ring B unsaturated estrogens with estrogen receptors of human endometrium and rat uterus. AB - The present investigation was undertaken to compare the binding affinities (Ka) of the ring B unsaturated equine estrogens (equilin [Eq], equilenin [Eqn], 17 beta-dihydroequilin [17 beta-Eq], 17 beta-dihydroequilenin [17 beta-Eqn], 17 alpha-dihydroequilin [17 alpha-Eq], and17 alpha-dihydroequilenin [17 alpha-Eqn]) and the classic estrogens (estrone [E1], 17 beta-estradiol [17 beta-E2], and 17 alpha-estradiol [17 alpha-E2]) for estrogen receptors in human endometrium and rat uterus. In both species, the ring B unsaturated estrogens bind with cytosol and nuclear receptors with high affinity (Ka x 10(9) M-1). The relative binding affinities of these estrogens were measured by determining the amount of unlabeled estrogen required to reduce by 50% the specific binding of [3H]17 beta Eq to endometrial cytosol receptors. The order of activity found was 17 beta-Eq greater than 17 beta-E2 greater than 17 beta-Eqn greater than E1 greater than Eq greater than 17 alpha-Eq greater than 17 alpha-E2 greater than 17 alpha-Eqn greater than Eqn. Essentially the same order of activity was observed when the apparent affinity constants of these estrogens for human and rat cytosol and nuclear receptors were determined by a competitive (inhibition) binding assay. Sucrose density gradient analysis indicated that these estrogens form protein complexes with cytosol and nuclear preparation that sediment at approximately 8S and 4S, respectively. The affinity constants for 17 beta-Eq were approximately two- to six-fold higher than E2 in both species. In a rat uterotropic assay, all nine estrogens were uterotropic. These data indicate that all ring B unsaturated estrogens present in conjugated equine estrogen preparations are biologically active and they express their biologic effects in the human endometrium by mechanisms similar to those described for the classic estrogens. PMID- 1871788 TI - Transplantation. Presidential address. PMID- 1871787 TI - Preclinical evaluation of a new potent immunosuppressive agent, rapamycin. AB - Since individual immunosuppressive agents display pleiotropic arrays of nonimmunologic toxic complications when used at therapeutic concentrations, synergistic drug combinations proffer an attractive strategy. RAPA is a good candidate for this enterprise, because of its unique action to inhibit lymphokine signal transduction. Initial in vivo and in vitro studies using the rigorous pharmacologic tool, the median effect analysis, document a synergistic relation between RAPA and CsA in rodent and canine models. These preclinical findings compel careful Phase I trials, in order to assess the safety and synergistic efficacy of RAPA in combination drug regimens with other immunosuppressive agents. PMID- 1871789 TI - Chronic renal allograft rejection. Selective involvement of the glomerular endothelium in humoral immune reactivity and intravascular coagulation. AB - To study immune reactive and thrombotic mechanisms involved in chronic renal allograft rejection, Lewis rat kidneys were transplanted into bilaterally nephrectomized Brown Norway recipients tolerant of LEW erythrocyte antigens. Such BN rats fail to produce anti class I MHC alloantibodies after insertion of a LEW kidney. The LEW renal allografts experience a transient rejection episode without proteinuria followed by the development of chronic rejection, clinically characterized by glomerular proteinuria in the presence of stable renal function. Immunohistological studies of such chronically rejected LEW renal allografts showed the occurrence of glomerular and interstitial infiltration of predominantly monocytes and T cells. CD4-positive T cells dominated over CD8 positive T cells in the chronically rejected LEW renal grafts. IgG deposition was found deposited throughout the renal vasculature--this in contrast to IgM, which was observed only in the glomerular vasculature. Glomerular antibodies were not directed to endothelial class II MHC antigens, and showed only weak complement fixation as demonstrated by C3 staining. Selective glomerular IgM deposition was associated with vascular (platelet-containing) thrombi, and focal and segmental fibrinoid necrosis. In contrast, acutely rejected LEW renal grafts in unmodified BN recipients showed IgM deposition as well as thrombus formation throughout the entire renal vasculature. The results demonstrate that the antibody response to endothelial--and, in particular, glomerular endothelial non-MHC antigens--may bring about chronic vascular renal allograft rejection. How the formation of glomerular thrombotic lesions may be assisted by endothelial reactivity to cytokines from local immune reactive cells is discussed. PMID- 1871790 TI - Toxicity of rapamycin--a comparative and combination study with cyclosporine at immunotherapeutic dosage in the rat. AB - Sprague-Dawley rats were treated for 14 days with rapamycin (RAP; 1.5 mg/kg/day i.p.), cyclosporine (15 mg/kg/day by gavage), both drugs in combination, or appropriate drug vehicles. Hematological parameters and biochemical indices of renal and hepatic function were determined throughout the experimental period, at the end of which the rats were killed and tissues examined histologically. There was a significant reduction in weight gain in RAP- but not CsA-treated animals, while rats given both drugs showed a reduction in body weight over the 14-day experimental period. There were no significant alterations in absolute or differential white blood cell counts or in T or B cell numbers, except in the drug combination group, in which an absolute lymphopenia was detected on day 14. Small but significant increases in urinary flow rate (UFR) were found with either drug alone, and there was a marked (4-fold) increase in UFR in response to drug combination. Both RAP and CsA caused a small elevation in serum creatinine concentrations, but only with CsA was there a significant elevation in urinary enzyme activity and reduction in 51Cr. EDTA clearance. The drug combination exacerbated renal impairment, the extent of which was greater than the additive effect of either drug alone. Hyperbilirubinemia of similar magnitude was observed in rats receiving either CsA alone or in combination with RAP. In contrast to its effect on renal function, however, the CsA+RAP combination was without additional effect on liver function compared with the minor changes seen with either drug alone. Plasma and urinary glucose levels were elevated in all drug treatment groups and especially in animals given both drugs. RAP administration did not significantly affect whole-blood CsA concentrations, although the possibility of a pharmacokinetic interaction cannot be totally excluded. Histological studies revealed striking thymic medullary atrophy in all drug-treated animals. In addition, all rats given RAP showed focal myocardial necrosis of overall mild moderate severity. Kidneys of RAP-treated rats appeared normal, whereas mild, focal, acute tubular necrosis was evident in all CsA-treated animals. Pancreases of all drug-treated animals were normal. PMID- 1871791 TI - Automated large-scale isolation, in vitro function and xenotransplantation of porcine islets of Langerhans. AB - To evaluate the potential of utilizing porcine islet tissue as an alternative to human islet tissue for transplantation, we developed a method for the isolation of large amounts of highly purified porcine islets, and assessed the in vitro and in vivo function of the isolated islets after 1, 4, and 7 days of culture. The pancreatic duct of the splenic lobe was cannulated and distended by injection of Hanks' balanced salt solution containing 1.5 mg/ml collagenase. The pancreas was then processed by a modification of the automated digestion-filtration method developed in this laboratory, and with purification accomplished by Euro-Ficoll gradients (dialyzed Ficoll in Eurocollins solution), consisting of two layers of 1.108 and 1.091 g/cm3 density, topped with a layer of HBSS. The postpurification yield was 5203 +/- 645 (mean +/- SEM) islets per gram of pancreas with a number of islet equivalents (IE) per gram pancreas (islet equivalence: 150-microns-sized islets) of 3551 +/- 305, and a volume of 6.27 +/- 1.7 mm3 islet tissue per gram of pancreas. The islet purity exceeded 90%. Overnight-cultured, perifused porcine islets released 53.1 +/- 8.2 pM insulin/200 IE at 3.3 mM glucose, and 114.9 +/- 25.4 pM insulin/200 IE at 16.7 mM glucose (P less than 0.001 vs. basal output). When theophylline was added, insulin secretion increased to 264.2 +/- 63.2 pM/200 IE (P less than 0.001 vs. basal secretion and P less than 0.005 vs. secretion at 16.7 mM glucose). After 4 days of culture, the islets still responded to secretagogues. The functional integrity of the isolated islets was confirmed by reversal of diabetes in aL3T4 antibody-treated C57B/B6 diabetic mice: normoglycemia was promptly restored by transplanting 1000 overnight- or 7-day cultured (24 degrees C) islets under the kidney capsule. These results suggest that continued improvements of porcine islet isolation and culture could permit the use of porcine islets in immunoalteration and immunoisolation studies that may lead to eventual human transplantation. PMID- 1871792 TI - Immunopathology of hyperacute xenograft rejection in a swine-to-primate model. AB - Hyperacute rejection is the inevitable consequence of the transplantation of vascularized organs between phylogenetically distant species. The nature of the incompatibility and the pathogenetic mechanisms that lead to hyperacute xenograft rejection are incompletely understood. We investigated these issues by the immunopathological analysis of tissues from swine renal and cardiac xenografts placed in rhesus monkeys. Hyperacute rejection was associated with deposition of recipient IgM and classic but not alternative complement pathway components along endothelial surfaces, the formation of platelet and fibrin thrombi, and the infiltration of neutrophils. In animals from which natural antibody was temporarily depleted by organ perfusion, rejection was observed at 3 days to 5 days posttransplant. The immunopathology of rejection in these tissues revealed focal vascular changes similar to those observed in hyperacute rejection. A xenograft functioning for a prolonged period in a recipient temporarily depleted of circulating natural antibody contained recipient IgM along endothelial surfaces but no evidence for significant deposition of complement, formation of platelet and fibrin thrombi, or infiltration of neutrophils. These results suggest that rhesus IgM contributes significantly to the development of hyperacute rejection in the swine to Rhesus model and that the fixation of complement is a critical factor in the recruitment of the coagulation cascade and platelet aggregation--and possibly in the adherence and infiltration of PMN. PMID- 1871794 TI - Sixty-minute normothermic liver ischemia in rats. Evidence that allopurinol improves liver cell energy metabolism during reperfusion but that timing of drug administration is important. AB - Allopurinol (ALL) improves energy metabolism in organs subjected to ischemia reperfusion injury. The importance of different administration schedules of ALL has been studied in a rat liver model exposed to 60 min of normothermic ischemia followed by reperfusion. ALL (100 mg/kg) that administered in two doses, one prior to ischemia and one prior to reperfusion, improved production of adenosine triphosphate in the liver as well as bile flow during reperfusion. ALL administered in a single dose, either prior to ischemia or prior to reperfusion, was less effective. The concentration of hypoxanthine during ischemia increased in the groups given ALL prior to induction of ischemia. Based on the present findings, we argue that the beneficial effect of ALL administration can be potentiated by different drug-administration schedules. Our data also suggest that the prime mechanism of action for ALL is not only related to inhibition of free-oxygen-radicals production but that preservation of hypoxanthine, which can be used for ATP resynthesis and the scavenging properties of ALL itself, may be equally important. PMID- 1871793 TI - Increase in survival of liver grafts after rinsing with warm Ringer's solution due to improvement of hepatic microcirculation. AB - Temperature increases membrane fluidity and decreases vascular resistance in isolated organs. Therefore, these studies were designed to determine if a rinse with warm buffer could increase survival time in the rat model of orthotopic liver transplantation by improving hepatic microcirculation. Brief periods of warm ischemia (3-8 min) did not damage the liver as indexed by minimal release of LDH. Survival of rats for 30 days was greater than 90% in this model when livers were stored for 1 hr in Ringer's solution; yet grafts stored for 8 hr in Euro Collins solution and rinsed with 20 ml of cold (0-4 degrees C) Ringer's solution survived postoperatively only around 3 days. However, livers stored for 8 hr in Euro-Collins and rinsed with 20 ml of warm (37 degrees C) Ringer's survived longer than 30 days (i.e., permanently). Serum transaminase levels reached peak values around 6000 U/L one day postoperatively in the cold-rinsed group, and liver injury assessed histologically was substantial. Under these conditions, pulmonary infiltration of inflammatory cells was observed in about 23% of lung tissue examined and was associated with massive bleeding. Following a warm rinse, however, maximal SGOT levels and injury to both liver and lung were reduced significantly by 80-90% 24 hr postoperatively. Moreover, the warm rinse improved hepatic microcirculation. It accelerated blood flow into the liver approximately two-fold, as indexed by the half-time of changes in hemoglobin reflectance from the liver surface, improved the distribution of colloidal carbon in the organ observed macroscopically, and decreased vascular resistance by over 50%. These data support the hypothesis that a brief rinse of liver grafts with warm buffer markedly improves the hepatic microcirculation, leading to dramatic improvement in graft survival. This work demonstrates clearly that a brief warm rinse may be useful clinically in liver transplantation. PMID- 1871795 TI - Evidence that LS-2616 (linomide) causes acute rejection of rat allografts protected by cyclosporine but not of long-term surviving allografts. AB - The immunomodulator LS-2616 (Linomide) induces rejection of cyclosporine protected rat cardiac allografts. The aim of this study was to characterize this rejection in the presence of CsA and to test LS-2616 in other models of permanent graft acceptance in the rat. PVG rat hearts were transplanted heterotopically to Wistar/Kyoto (Wi/Ky) rat recipients on day 0. The recipients were treated orally on days 0-9 with CsA (10-40 mg/kg) and/or with LS-2616 (2.5-160 mg/kg) starting at different times (day -7 -+5) until the day of complete rejection. The addition of LS-2616 (day -1--stop) to CsA (10 mg/kg) resulted in a dose-dependent antagonism of the immunosuppressive effect of CsA with daily doses of 2.5-160 mg/kg. Furthermore, the results were similar, irrespective of whether LS-2616 treatment (160 mg/kg) was started on day -7, -1, +1, +3, or +5. LS-2616 (160 mg/kg) pretreatment of the recipient for 7 days before transplantation was considerably less effective. CsA (20 mg/kg) for 14 days after a PVG to DA transplantation resulted in permanent graft survival. This was not abrogated by LS-2616. Neither was rejection induced in long-term surviving grafts of RT1.C incompatible Lewis recipients. Our data suggest that LS-2616 activates already stimulated and sensitized T cells that are otherwise controlled by CsA. PMID- 1871796 TI - Progression of kidney disease in chronic renal transplant rejection. AB - The rate of progression of renal insufficiency was quantitated from reciprocal of serum creatinine versus time plots in patients with clinical and histologic evidence of chronic renal transplant rejection. The plots were evaluated by the breakpoint test. This method identifies breakpoints in a linear plot and compares the statistical significance of the fit provided by two intersecting lines with that of a single straight line. The breakpoint test when applied to the 22 patients with a significant linear correlation between the reciprocal of serum creatinine versus time detected a change in the slope in 20 cases (90.9%) indicating the presence of a breakpoint. The average diastolic, systolic, and mean arterial pressures before the breakpoint were significantly correlated with the value of the serum creatinine at the time of the change of the slope (r = 0.45, P less than 0.05; r = 0.58, P less than 0.01; r = 0.56, P less than 0.05, respectively) demonstrating more severe hypertension in those patients with the more severe renal dysfunction. The slope after the breakpoint was significantly correlated with the mean diastolic blood pressure values after the breakpoint (r = 0.48, P less than 0.05) with higher pressures being found in those patients with faster rates of decline in renal function. Both before and after the breakpoint occurred, the rate of progression of the renal disease, as estimated by the reciprocal of serum creatinine versus time plot, was greater when the mean diastolic blood pressure was higher than 90 mmHg. In conclusion, the vast majority of patients with proven chronic rejection progress linearly although a change in the rate of progression was frequent. Higher levels of blood pressure correlate with greater rates of progression of renal insufficiency, and a faster progression associates with a diastolic blood pressure greater than 90 mmHg. PMID- 1871797 TI - Risk factor analysis for the major hazards following heart transplantation- rejection, infection, and coronary occlusive disease. AB - This study demonstrates the importance of analyzing survival by cause of death in order to achieve a better understanding of the prognostic indicators involved. It further emphasizes the need for analysis of risk factors in both univariate and multivariate models, and the danger of making judgements based on premature analysis of data on follow-up after heart transplantation. Survival following transplantation is characterized by the major hazards of early death due to infection and rejection and late graft loss due to coronary occlusive disease (COD). This study summarizes the first-graft survival experience for 323 transplant patients at Papworth Hospital, and assesses a number of potential risk factors for (1) early mortality, (2) late mortality from COD, and (3) development of COD. The potential risk factors considered for all hazards are donor and recipient age, sex, blood group, and matching of these factors; donor cause of death and recipient immunosuppression; inotropic support; waiting time; preoperative diagnosis and previous cardiac surgery; ischemic time; and extubation time. In addition, for development of, and graft loss from, COD, perioperative rejection and cytomegalovirus infection; hypertension at discharge; and cholesterol, triglycerides, and lipids at two years were assessed as risk factors. Advances in immunosuppression were observed to have increased overall survival rates and decreased mortality from infection, rejection, and COD, as well as decreasing morbidity from COD. Fatal rejection was found to be more likely in female recipients, recipients over 40 years, recipients of grafts from donors over 30 years old, patients who were transplanted for valvular heart disease, and patients who waited less than three months for their transplant. Male recipients of female donor organs were more likely to lose their grafts as a result of COD. Patients older than 50 and hearts from donors older than 40 conferred a high risk of development of and loss from COD. Patients transplanted for ischemic heart disease were more likely to develop COD. High cholesterol, low HDL, high LDL, and high triglycerides at two years after transplant showed some evidence of high risk for the subsequent development of COD, although these relationships are not statistically significant at this stage. Contrary to other recent studies, cytomegalovirus infection was not found to be a risk factor for the development of COD. PMID- 1871798 TI - Risk factors for second renal allografts immunosuppressed with cyclosporine. AB - Second renal allograft survival rates are lower than those of primary allografts. For recipients immunosuppressed with azathioprine, prednisone, and Minnesota ALG (conventional immunosuppression), risk factors associated with decreased second graft survival have been identified: age greater than 40, cadaver donor, less than 6 months between primary graft loss and retransplantation, duration of primary graft function (6 months or 1 year, depending on the study), high peak panel-reactive antibody, number of human leukocyte antigen mismatches, and delayed graft function. In this study, we used a multivariate analysis to identify risk factors associated with decreased second graft survival in patients who did or did not receive cyclosporine. Results were compared with primary graft survival rates. Risk factors for patients receiving conventional immunosuppression were: (a) primary graft loss caused by rejection greater than or equal to 6 months (P = 0.01 vs. either rejection less than 6 months or nonimmunologic loss); (b) cadaver donor (P = 0.005 vs. living related); and (c) interval between primary graft loss and retransplantation of greater than or equal to 6 months (P = 0.05 vs. less than 6 months). For CsA, risk factors that most decreased second graft survival were: (a) primary graft loss caused by rejection less than 6 months (P = 0.11 vs. nonimmunologic loss); (b) conventional immunosuppression for the primary graft (P = 0.08 vs. CsA immunosuppression); and (c) a peak PRA of greater than or equal to 21 (P = 0.14 vs. peak PRA of 1-20). For second graft recipients immunosuppressed with CsA, primary graft loss to either rejection greater than 6 months posttransplant or nonimmunologic causes was not a risk factor for second graft survival. These data extend the recent reports of other investigators by identifying risk factors for retransplant recipients treated with CsA and by demonstrating that subgroups of patients in the retransplant population can be retransplanted without additional risk (i.e., their second graft survival rates are similar to primary graft survival rates). This may become more important if, in the future, organ distribution is based on graft survival data. If so, our data would support retransplantation in patients who are immunosuppressed with CsA, especially those who lost their primary graft to either rejection greater than or equal to 6 months posttransplant or nonimmunologic causes; who receive living related grafts; and who have a peak PRA of 1-20. PMID- 1871799 TI - Immunocytology of urinary sediments as a method of differentiating acute rejection from other causes of declining renal graft function. AB - We have previously reported that during acute rejection of renal allografts T lymphocytosis and increased HLA-DR expression on tubular epithelial cells can be demonstrated in urinary sediments by incubating cytospin preparations with monoclonal antibodies against T cells and HLA-DR antigen in an indirect alkaline phosphatase technique. We now tested whether immunocytological analysis of urinary sediments can be used to differentiate acute rejection from other causes of declining graft function. For this we retrospectively selected, from a series of urinary samples that were taken either at random or as part of a longitudinal study in unselected graft recipients, those specimens that were taken at the time of increasing creatinine levels, and compared the original immunocytological diagnosis, made without knowledge of clinical data, with the final clinical one. In 44 of 74 evaluable cases an immunocytological diagnosis of rejection was made, which in 37 patients was consistent with the eventual clinical diagnosis. In 28 of 30 cases the diagnosis no rejection proved to be correct. This indicates a sensitivity of 95% and a specificity of 80% for the immunocytological diagnosis of rejection. Of 38 patients who underwent a renal core biopsy, the immunocytological diagnosis was consistent with the histological diagnosis in 36 cases (31 rejections, 5 no rejections). In this subgroup the sensitivity of the immunocytology was 97% and the specificity 83%. We conclude that immunocytological examination of urinary sediments in renal allograft recipients can be a valuable new tool in discriminating acute interstitial rejection from other causes of deteriorating graft function. PMID- 1871800 TI - Evidence that addition of azathioprine improves renal function in cyclosporine treated patients with allograft dysfunction. AB - Several approaches have been attempted to manage renal allograft dysfunction in cyclosporine-prednisone (CsA-Pred)-treated patients. Conversion to conventional therapy and perioperative triple drug have been associated with high rates of acute rejection episodes, infections, or neoplasms. We report our experience in delayed addition of azathioprine (1-2 mg/kg/day) to CsA/Pred protocol in three groups of patients. Group I (n = 9) had chronic renal function deterioration due to chronic rejection; group II (n = 10) had repeated or severe acute rejection episodes despite adequate CsA levels; and group III (n = 8) had CsA toxicity despite drug tapering. In group I, serum creatinine (SCr) had risen from 2.2 +/- 0.9 to 2.9 +/- 0.7 mg/dl over the 6 months prior to Aza addition (P less than 0.05), renal function declining at a rate of -0.14 +/- 0.12 Cr-1/year. In the 6 month post-Aza, renal function improved at a rate of 0.06 +/- 0.06 Cr-1/year and during the entire follow-up at a rate of 0.04 +/- 0.12 Cr-1/year (P less than 0.05) with stable CsA levels (288 +/- 167 vs. 251 +/- 172 ng/dl, NS). In group II response was worse, though the rate of declining renal function prior to Aza ( 0.10 +/- 0.10 Cr-1/year) was almost stopped after Aza. In group III there was very good response to Aza addition, as 7 out of 8 patients improved graft function (baseline SCr 2.5 +/- 0.7 mg/dl vs. 1.9 +/- 0.6 mg/dl at last follow-up, P less than 0.05), with significantly decreased CsA levels (480 +/- 97 vs. 268 +/ 120, P less than 0.05). One patient from group II died from pneumonia, and 6 patients (1 from group I and 5 from group II) lost their grafts. Fifteen patients improved graft function, and 9 worsened after addition of Aza. The bad-responders had significantly higher SCr at baseline compared with the good-responders (3.8 +/- 1.8 vs. 2.7 +/- 0.6 mg/dl, P less than 0.01). Amelioration of chronic graft dysfunction can be achieved by delayed addition of Aza to CsA-Pred in patients with chronic rejection or CsA toxicity. This is accompanied by low rate of acute rejection, good patient and graft survival, and low rate of infections. A worse outcome can be seen in patients with high-baseline SCr levels, suggesting the need for addition of Aza in the initial chronic graft dysfunction. PMID- 1871801 TI - Effects of diltiazem upon metabolism and immunosuppressive action of cyclosporine in kidney graft recipients. AB - It is widely believed that calcium antagonists such as diltiazem exert immunosuppressive effects in kidney graft recipients--however, the mechanism is unclear. In a randomized controlled trial, kidney graft recipients who received diltiazem during transplantation and for an average of 12 months thereafter experienced significantly fewer rejection episodes than patients treated with cyclosporine and steroids alone. Furthermore, 1-year (97% vs. 85%) and 4-year (80% vs. 70%) graft survival rates were higher in diltiazem-treated patients, but the difference was not statistically significant. In vitro, diltiazem had little immunosuppressive activity. Concentrations of diltiazem which blocked the proliferation of PHA-stimulated human peripheral blood mononuclear cells, or prevented activation-associated accumulation of interleukin-2 mRNA, or p50- and p70-IL-2 receptor mRNA exceeded pharmacological concentrations by more than 100 fold. Both, CsA and high doses of diltiazem caused an increase of IL-6 mRNA. In contrast to these findings, the IL-6 plasma concentrations were comparable in both groups, whereas the serum concentration of soluble IL-2 receptors was decreased in patients treated with diltiazem. Administration of diltiazem caused an alteration of CsA metabolism. The whole-blood concentration of CsA metabolite 17 was significantly increased in diltiazem-treated patients, resulting in a five times-higher concentration of this metabolite in the cellular blood compartment compared with the parent drug. Changes in metabolites 1, 8, and 18 levels were less pronounced. Although direct immunosuppressive properties of diltiazem are unlikely, diltiazem could support immunosuppression by altering CsA metabolism, and promoting accumulation of certain metabolites. PMID- 1871802 TI - Effect of anti-LFA1 (CD11a) monoclonal antibodies in acute rejection in human kidney transplantation. AB - A murine IgG1 monoclonal antibody, 25-3 (Immunotech, France), directed against the alpha chain (CD11a) of the human LFA1 molecule was used in the treatment of 7 histologically documented first acute rejection in first kidney transplantations under cyclosporine. Four patients (group I) received 20 mg/day for 2 days and 10 mg/day for 8 days of 25-3 MoAb. One developed Quincke's edema after the first injection of 25-3 and was immediately withdrawn from the study. In 2 patients, whose serum creatinine continued to increase, 25-3 MoAb was replaced by steroids, followed by ALG after 3 and 4 days of treatment, respectively. In the last case, rejection was reversed by 25-3 MoAb alone. As the clinical response of rejection to 25-3 was poor, another group of 3 patients (group II) was treated with 25-3 at a dose of 40 mg/day for 2 days, 20 mg/day for 2 days, and 10 mg/day for 6 days, but 25-3 was still unsuccessful in reversing acute rejection, and rescue treatment was initiated between days 5 and 8 in all cases. MoAb tolerance was excellent in 3 patients. With the exception of the one case of Quincke's edema, only minor side effects were noted in the last 3 recipients. 25-3 MoAb serum trough levels peaked between 1.5-3.5 micrograms/ml at day 3 in group I and between 2-9 micrograms/L at day 2 in group II. Surprisingly, only one patient, in group I, exhibited a borderline IgG immune response against 25-3. These findings suggest that the 25-3 anti-CD11a MoAb is ineffective in controlling the course of acute rejection in kidney transplantation. However as already reported for another anti-LFA1 or with an anti-CD4 MoAb in mouse, 25-3 would be the first example in humans of a MoAb that does not elicit a strong immune response against its own determinants. This property might have important applications if 25-3 can prevent rejection in a prophylactic protocol or block the immune response against other MoAbs. PMID- 1871803 TI - Intraoperative estimation of endotoxin, TNF alpha, and IL-6 in orthotopic liver transplantation and their relation to rejection and postoperative infection. AB - The course of endotoxemia, TNF alpha, and IL-6 during orthotopic liver transplantation was studied in 28 transplantations performed in 27 patients to evaluate their impact on early postoperative rejection and infection. The preoperative levels of endotoxin, TNF alpha, and IL-6 were not different in patients who did or did not develop postoperative rejection and/or infection within the first 10 postoperative days. At the end of surgery, TNF alpha levels increased in patients who developed rejection (median 100 pg/ml vs. 11.5 pg/ml, P = 0.004). A TNF alpha level of greater than 100 pg/ml at the end of transplantation predicted rejection in 82% of the patients. During surgery, IL-6 levels increased significantly in patients with subsequent postoperative infection, reaching significance after revascularization of the graft (median 975 pg/ml vs. 185 pg/ml, P = 0.006). An IL-6 cutoff level of 800 pg/ml predicted postoperative infection in 75% of the patients. Endotoxins were elevated intraoperatively in patients with postoperative infection, but the difference did not reach significance. There was no prognostic relevance with respect to the intraoperative values of TNF alpha and infection or IL-6 values and rejection. An intraoperative elevation of TNF alpha seems to precede early postoperative rejection, and highly increased IL-6 may be a predictor of subsequent infection in human liver transplantation. PMID- 1871804 TI - Does histologic acute rejection in lung allografts predict the development of bronchiolitis obliterans? AB - Clinical acute lung rejection (AR) occurs in lung allografts usually within 50 days after transplantation. While perivascular infiltrates characterize AR, with moderate-to-severe acute rejection small airway injury occurs. We investigated the significance of small airway injury in AR and its relationship to the development of bronchiolitis obliterans (OB) in 11 recipients of combined heart lung or double-lung allografts. In general, the intensity and persistence of early acute rejection episodes associated with injury to bronchioles correlated with the development of histologic bronchiolitis obliterans. Early AR may "prime" lymphocytes for subsequent respiratory epithelial injury and airway fibrosis late in the postoperative period. PMID- 1871805 TI - Cyclosporine-associated seizures in bone marrow transplant recipients given busulfan and cyclophosphamide preparative therapy. AB - Five of 182 recipients of allogeneic bone marrow transplants performed between 2/84 and 6/90 developed seizures while receiving cyclosporine and methylprednisolone to prevent acute graft-versus-host disease. All received a radiation-free regimen of busulfan and cyclophosphamide as preparative therapy. Two patients received HLA-mismatched allografts; and three patients received marrow from HLA-identical sibling donors. Two patients had received extensive intrathecal therapy prior to transplantation. All patients were receiving standard prophylactic doses of CsA and MP at the time of onset (median 31 days posttransplantation) of seizures. Three patients had mild-to-moderate hypertension and varying degrees of morphologic evidence of microangiopathic hemolytic anemia. None had unusually low magnesium levels. Cyclosporine levels were not in the toxic range. Cranial magnetic resonance imaging and computed tomography (CT) showed bilateral abnormalities primarily in the posterior temporal, occipital, and parietal lobes. These abnormalities were shown to be transient on sequential MRI exams in two patients. Seizures as well as radiologic abnormalities resolved on stopping CsA and did not recur in 2 patients who subsequently received CsA in lower doses. These findings confirm and expand previous observations of CsA-associated seizures and demonstrate that they occur in allogeneic bone marrow transplant recipients following a radiation-free preparative regimen of busulfan and cyclophosphamide. PMID- 1871806 TI - Demonstration of local immunosuppression with methylprednisolone in the sponge matrix allograft model. AB - This study evaluated the effect of locally delivered methylprednisolone on the systemic and local immune response in the sponge matrix allograft model. Polyurethane sponges were coated with peritoneal exudate cells from DBA/2 (H-2d) or C57Bl/6 mice (H-2b) and placed subcutaneously in C57BL/6 recipients 24 hr later. Each mouse received both a syngeneic and an allogeneic sponge graft. Local immunosuppression was effected by placement on day 0 of cellulose/matrix pellets containing a preparation of increasing quantity of controlled release MP or by daily intrasponge injection of MP. Local immunosuppression was demonstrated by decreased cytotoxicity on day 12 in the allogeneic sponge receiving MP directly, as compared with the groups that received MP in the opposite syngeneic sponge or no MP. This effect was noted at a specific MP dose (0.5 mg/kg/day). Absolute numbers of precursor cytolytic cells and mature cytolytic cells (determined by limiting dilution analyses) infiltrating the allografts were also decreased in the sponges receiving MP directly, relative to the groups receiving MP in the opposite syngeneic sponge. Maintenance of systemic (in contrast to local) immunity was also demonstrated. Animals treated with local MP into a simultaneously placed syngeneic sponge or in whom no MP was delivered became sensitized to a synchronous DBA/2 sponge and rejected a subsequent DBA/2 skin graft in second-set fashion. Conversely, animals that received local MP into their synchronous DBA/2 sponge rejected a subsequent DBA/2 skin graft or a third party graft with first-set kinetics. The presence of local MP at the initial graft site prevented the animals from becoming sensitized to the presented alloantigen but did not keep the animal from developing a rejection response to a third-party skin graft with first-set kinetics. It appears that delivery of MP locally to the site of antigen is an effective method to modulate alloreactivity. In addition, the sponge matrix allograft appears to be a useful model for studying local immunosuppression. PMID- 1871807 TI - Immune responses to noninherited maternal RT1A antigens in inbred rats. AB - Humoral responses to non-inherited maternal class I antigens (class I NIMAs) were assessed in 3 groups of inbred rats expressing the RT1u phenotype. Group 1 consisted of the progeny of (AO X DA)F1 X PVG matings; their haplotype was RT1u/c and their non-inherited maternal haplotype RT1a. Group 2 were the progeny of (AO X LEW)F1 X PVG matings the haplotype of which was also RT1u/c, but their non inherited maternal haplotype was RT1l. Group 3 comprised 8 (AO X PVG)F1 (RT1u/c) hybrids. All rats received 2 intravenous blood transfusions (0.5 ml) from male DA (RT1Aa) donors on days 0 and 7. They were bled at weekly intervals for 6 weeks and again at 20 weeks after the first transfusion. Alloantibody responses to RT1Aa were assessed by an indirect hemagglutination assay (IHA)* and by a 51Chromium-release complement-dependent red cell cytotoxicity assay. All groups exhibited vigorous anti-class I antibody responses to the DA transfusions. No significant differences were detected, however, in antibody titers between the groups either by IHA or CDC or in the rates of decay of antibody titers up to week 20. In addition no blocking activity was found in sera obtained on day 0 from group 1 animals and tested for antiidiotypic antibody activity to cytotoxic anti-RT1Aa antibodies. In order to assess whether suppressor activity had been activated by the initial transfusions, in the animals in which class I NIMA was RT1Aa, all groups were rechallenged with a DA transfusion at week 20. All animals exhibited vigorous anamnestic responses to this challenge and no significant differences were detected between groups. In order to determine whether cellular tolerance to the noninherited maternal haplotype was present in group 1 animals, proliferative responses were assessed by one-way mixed lymphocyte cultures, using DA lymph node stimulator cells. No significant differences were detected in proliferative or kinetic responses between lymph node cells from rats the noninherited maternal haplotype of which was RT1a or from naive (AO X PVG)F1 hybrids. Peak proliferative responses to DA cells in rats the noninherited maternal haplotype of which was RT1l were similar, but maximal on day 4 as opposed to day 3. Hence in these inbred rat strains no evidence of humoral tolerance to class I NIMAs was detected. In addition there was no evidence of cellular tolerance to the noninherited maternal MHC haplotype. PMID- 1871808 TI - Effects of SMS 201-995 on the pharmacokinetic profile and cellular immune and toxic effects of cyclosporine in male Wistar rats. AB - The immunosuppressant cyclosporine and the long-acting somatostatin analog SMS 201-995 (octreotide acetate) may have to be given simultaneously in diseases such as pancreatic transplantation. The aim of the study was to evaluate the effects of SMS 201-995 on the pharmacokinetics of cyclosporine, and to assess whether the addition of SMS 201-995 altered some of the cellular immune and toxic (renal, hepatic, glucose tolerance) effects of cyclosporine. Male Wistar rats were treated with cyclosporine 10 mg/kg/day, SMS 201-995 100 micrograms/kg b.i.d., a combination of the two drugs, or the vehicle alone. The addition of SMS 201-995 delayed the peak plasma levels of cyclosporine without affecting the through levels, and did not alter the effects of cyclosporine on the mononuclear cell subsets. This combination caused significant increases in plasma creatinine and hepatic enzymes, suggesting renal and hepatic toxicity, and severe glucose intolerance. If present in humans, the appearance of severe glucose intolerance with combined administration of SMS 201-995 and cyclosporine for pancreatic transplantation could be misinterpreted as rejection and lead to inappropriate interventions. PMID- 1871809 TI - The immunochemical distribution of cyclophilin in normal mammalian tissues. AB - Cyclophilin, a 17 Kd proline cis-trans isomerase, high-affinity (Kd 10(-8) M) target for the immunosuppressive drug cyclosporine has ubiquitous phylogenic distribution, but its tissue localization in mammals has not been detailed. To explore a potential relationship between the multiple systemic effects of CsA and the cellular and tissue distribution of CYP, thirty-three different normal porcine tissues were examined using an immunohistochemical technique. Tissue was obtained from farmbred pigs, immediately fixed in buffered formalin, and prepared as embedded 5-mu sections. Immune-specific staining was accomplished using an ABC immunoperoxidase method and an affinity-purified, monospecific, rabbit anti-CYP IgG. Cut sections served as their own blanks and controls, and all tissues were stained in batch to minimize the effects of variation in technique. Consistent with earlier reports, CYP was present in all tissues studied, however, there was remarkable heterogeneity in CYP distribution. Renal parenchymal cells, cardiac and striated muscle, pulmonary and skin demonstrated cytoplasmic immunospecific CYP--however, the cellular localization varied. Cytoplasmic staining of endothelial, neural, and glandular elements was consistently observed. Contrasting with previous reports, CYP localized to the nucleus as well as the cytoplasm of some lymphoid cells, hepatocytes, and cells of the large intestine. Generally, greater CYP-specific staining was noted in organs amenable to CsA immunosuppression (heart, liver, kidney), compared with organs deemed more immunologically vulnerable when allografted under CsA (pancreas, lung, small bowel). Similarly, CYP-immunospecific staining was abundant in tissues susceptible to CsA toxicities (neural tissue, smooth muscle, kidney, liver). This detailed immunohistological examination affords a correlation between CYP content and sensitivity to CsA. It also raises some new questions about tissues with little extractable CYP but significant histological staining. PMID- 1871810 TI - Age-related differences in the effects of cyclosporine on lymphocyte intracellular free calcium. AB - The effect of cyclosporine on lymphocyte intracellular free calcium [( Ca2+]i) is controversial, and potential age-related differences in lymphocyte CsA sensitivity have not been studied. We measured the mitogen-induced change in [Ca2+]i in peripheral blood lymphocytes (PBLs) following intravenous CsA infusion (5 mg/kg) in neonatal pigs and found a significantly reduced calcium response compared with control (P = 0.02). This was associated with an elevation in resting [Ca2+]i in the neonatal PBLs 24 hr following the CsA infusion (P = 0.02). These changes in lymphocyte [Ca2+]i were associated with suppression of cell proliferation. Neonatal PBLs in mixed lymphocyte cultures showed a greater PHA induced change in [Ca2+]i (delta[Ca2+]i) compared with mature PBLs (P = 0.0007). The addition of CsA (1 microgram/ml) to mitogenic- and allogeneic-stimulated cultures did not affect resting [Ca2+]i or delta[Ca2+]i in either neonatal or mature PBLs. Our results demonstrate significant differences in calcium responses in neonatal lymphocytes following CsA infusion and allogeneic stimulation. This implies that there are age-related differences in CsA effects at or proximal to the level of calcium release and/or sequestration in the lymphocyte signal transduction pathway, and that elevated resting intracellular calcium levels may be indicative of reduced responsiveness, possibly through feedback inhibition of tyrosine kinase activity. PMID- 1871811 TI - HLA-DP incompatibilities and severe graft-versus-host disease in unrelated bone marrow transplants. PMID- 1871812 TI - Long-term follow-up of the fate of xenogeneic transplants of chondrocytes implanted into joint surfaces. PMID- 1871813 TI - Stability of reduced glutathione in solutions for organ preservation stored in multilayer bags versus EVA bags. PMID- 1871814 TI - Proceedings of a festschrift in honor of Paul S. Russell. November 30-December 1, 1990, Boston, Massachusetts. PMID- 1871815 TI - HLA peptide matching. AB - Thirty-eight HLA-A and -B locus specificities, for which the amino acid sequence is known, were cut by computer into all possible peptides composed of two to seven amino acids. These peptides were compared among the different specificities, and those that were unique were identified. For example, there were 375 unique tripeptides when considering both the A and B locus. The 1-year kidney graft survival was determined for patients who were mismatched for each of the tripeptides. The peptides were ranked according to the associated graft survival, and the sum of the ranks was used as a mismatching score. The rank sum score produced promising results, for some degree of correlation was noted when tested against another set of patients transplanted without CyA, and a third set of those who received grafts from related donors. We conclude that matching for tripeptides of the HLA-A and -B locus is associated with graft outcome, and that this may be a more effective way of HLA matching for transplants, particularly since a higher fraction of patients fall into the high-survival category. PMID- 1871816 TI - Organ sharing--must or myth? PMID- 1871817 TI - Factors affecting early diagnosis of organ allograft rejection. PMID- 1871818 TI - The pathogenesis of vascular rejection. PMID- 1871819 TI - Tolerance: past, present, and future. PMID- 1871820 TI - Studies in rodents on the use of polyclonal antilymphocyte serum and donor specific bone marrow to induce specific unresponsiveness to skin allografts. PMID- 1871821 TI - The impact of infection on the outcome of transplantation. AB - The risk of infection in the transplant patient is determined by two factors: the net state of immunosuppression and the environmental exposures the patient encounters. Those infections that do occur in the transplant patient are strongly modulated by the type, intensity, duration, and sequence of immunosuppressive agents administered. A central role in the pathogenesis of all forms of infection in the transplant patient is played by the immunomodulating viruses, particularly cytomegalovirus. Prevention of infection is far better than treatment; when prevention fails and clinical disease develops, patient and allograft survival are directly related to the speed with which diagnosis is made and specific therapy instituted. In order to prevent disease, both antimicrobial prophylaxis and preemptive therapy are being increasingly employed, particularly to blunt the side effects of intensive antirejection therapy. PMID- 1871822 TI - The present and future of kidney transplantation. PMID- 1871823 TI - Update on liver transplantation. PMID- 1871824 TI - Status report on pancreas transplantation. PMID- 1871825 TI - Cardiac transplantation: current indications and limitations. PMID- 1871826 TI - Current status of lung transplantation. AB - Techniques and indications for single and bilateral lung transplantation have evolved significantly in the past several years. Lung transplantation has entered a new era in which transplantation can be achieved with the same degree of success as that achieved with other major organ transplants. Many problems, common to organ transplantation remain to be solved including availability of suitable donor organs, improved immunosuppressive regimens, and the ability to properly diagnose and effectively treat organ rejection. PMID- 1871827 TI - An alternative view minimizing the significance of cyclosporine nephrotoxicity and in favor of enhanced immunosuppression for long-term kidney transplant recipients. PMID- 1871828 TI - Immunobiology of bone marrow transplantation as treatment for hematologic malignancies. AB - In conclusion, graft-versus-leukemia is important to prevent leukemia relapse following allogeneic bone marrow transplantation. This beneficial GVL effect is at least partly mediated by T-lymphocytes and is greatest in transplants from HLA nongenotypically identical donors. GVL is associated with the presence of GVHD, although preliminary studies suggest it may be possible to separate these two processes. Improvement in treatment results requires innovative effective therapies to enhance the direct antineoplastic effects of the preparative regimen or immune-mediated antileukemia mechanisms. PMID- 1871829 TI - The role of immunoglobulin in bone marrow transplantation. AB - Bone marrow transplantation has proven its value as a therapeutic approach to a variety of human diseases, primarily the hematopoietic malignancies. The major clinical problems preventing successful outcome of marrow transplant have been defined and therapeutic approaches to preventing or treating these complications have led to increased long-term disease survival. Passively administered antibody given as intravenous immunoglobulin has been studied as a therapeutic modality following bone marrow transplantation. Studies have demonstrated the efficacy of immunoglobulin in reducing bacterial infections in the posttransplant period; reducing severe CMV infections in allogeneic marrow transplant recipients who are seronegative for the virus and susceptible to primary infection; reducing mortality from CMV pneumonia in combination with ganciclovir; and reducing acute graft-versus-host disease following allogeneic BMT. In many cases alternate therapeutic strategies offer comparable or greater efficacy (eg, selective CMV negative blood products for CMV seronegative allogeneic BMT recipients receiving bone marrow from a seronegative donor). However, it is clear that intravenous immunoglobulin has a place in the therapeutic armamentarium of bone marrow transplantation. Future controlled clinical trials are necessary to establish its exact role and to define which preparations and dose schedules provide the greatest therapeutic benefits. PMID- 1871830 TI - Prospects in transplantation. PMID- 1871831 TI - Studies of privileged sites and islet transplantation. PMID- 1871832 TI - Imaging and quantitation of renal transplant rejection in the rat by in vivo use of 111In labelled antilymphocyte and anti-class I and II major histocompatibility complex monoclonal antibodies. PMID- 1871833 TI - Innovative use of organs for liver transplantation. PMID- 1871834 TI - New approaches to transplantation tolerance. PMID- 1871835 TI - Impact of cyclosporine on organ transplantation. PMID- 1871836 TI - Why is the pancreas special? PMID- 1871837 TI - Triple therapy. PMID- 1871838 TI - Long-term survival after renal transplantation: observations beyond 10 years. PMID- 1871839 TI - Rehabilitation of recipients with a functioning renal allograft for 10 or more years. PMID- 1871840 TI - Azathioprine enhances experimental amyloidosis and attenuates colchicine protection against organ deposition of amyloid. PMID- 1871841 TI - Does immunosuppression alter the growth of metastatic liver carcinoid after orthotopic liver transplantation? PMID- 1871842 TI - The influence of immunosuppression on the prevalence of aseptic bone necrosis after renal transplantation. PMID- 1871843 TI - Beneficial effect of pretreatment with azathioprine on warm and cold ischemia of the swine liver. PMID- 1871844 TI - Problems with immunosuppression in developing countries. PMID- 1871845 TI - Dual vs triple immunosuppressive therapy: equally safe and effective in kidney transplantation? PMID- 1871846 TI - Preliminary results of a prospective randomized clinical trial comparing cyclosporine A to antithymocyte globulin immunosuppressive induction therapy in kidney transplantation. PMID- 1871847 TI - Renal transplantation with and without cyclosporine: results at 6 years in a Lisbon series of 516 cases. PMID- 1871848 TI - Long-term cyclosporine A treatment does not progressively impair renal graft function: a 5-year follow-up study. PMID- 1871849 TI - Progressive systemic sclerosis and renal transplantation: a contraindication to the use of cyclosporine A? PMID- 1871850 TI - Effects of combined therapy with prostaglandin E1 and cyclosporine A on rat heart allograft survival. PMID- 1871851 TI - Pancreas transplantation at Cambridge: more than 10 years of experience at the cyclosporine era. PMID- 1871852 TI - Survival of renal allografted dogs after limited therapy with cyclosporine and the PAF antagonist WEB 2170. PMID- 1871853 TI - Cyclosporine levels together with metabolites are more effective than cyclosporine parent compound levels alone in predicting hepatic toxicity after liver transplantation. PMID- 1871854 TI - Experience with triple immunosuppressive therapy in living related donor kidney transplantation. PMID- 1871855 TI - Maintenance immunosuppression without corticosteroids following combined pancreas and kidney transplantation. PMID- 1871856 TI - Sequential discontinuation of azathioprine and prednisone in renal transplantation. AB - We report the time course of rejections in 110 patients of first cadaver kidney grafts entered into a randomized controlled trial of induction ALG vs continuous IV CyA, with both groups receiving Aza for 30 days and Pred for 3 months. There was no difference in 1-year graft or patient survival in the two induction regimens. Despite a slight delay in time to first rejection, the number, severity, and outcome of rejections were the same in both. Fifty percent of patients never had a rejection, and 80% of these were on CyA monotherapy at 1 year vs only 22% in patients with rejections. Thirty-five percent had a rejection in the first month, and one fourth of these had a repeat in the second month. The risk of graft loss was 10% with a first, 38% with a second, and 50% with a third rejection. First rejections occurring after 30 days rarely caused graft loss and rejection after 90 days proved to be unusual. PMID- 1871857 TI - Need for subsequent surgery in 525 kidney transplants with and without cyclosporine. PMID- 1871858 TI - Rapamycin suppresses in vitro immunoglobulin production by human lymphocytes. PMID- 1871859 TI - Reversal of ongoing rejection of allografts by rapamycin. PMID- 1871860 TI - Early immunological benefits of glutathione-supplemented UW solution in hepatic transplantation. PMID- 1871861 TI - Rapamycin in experimental renal allografts in primates. PMID- 1871862 TI - Tolerogenic and immunosuppressive properties of liver grafts in animals and man. PMID- 1871863 TI - New strategies of heparin treatment used to prolong allograft survival. PMID- 1871864 TI - Interaction of purified HLA class I molecules with alloreactive CTL. PMID- 1871865 TI - Plasma MHC class I expression in cardiac graft patients: donor-specific soluble antigen in a presensitised graft patient. PMID- 1871866 TI - Is primary nonfunction still a suitable indication for liver retransplantation? PMID- 1871867 TI - Intraoperative trends of oxygen consumption and blood lactate as predictors of primary dysfunction after liver transplantation. PMID- 1871868 TI - Treatment of acute rejection following liver transplantation: a comparison between methylprednisolone and hydrocortisone. PMID- 1871869 TI - Immunologic monitoring in kidney transplantation. PMID- 1871870 TI - Hamster to rat xenografts are not rejected primarily by rat T cells. PMID- 1871871 TI - Donor pretreatment prolongs survival of discordant xenografts. PMID- 1871872 TI - Improvement in renal transplant function after subtotal parathyroidectomy in a hypercalcemic kidney allograft recipient. PMID- 1871873 TI - Renal cell carcinoma in a liver transplant recipient. PMID- 1871874 TI - Protective effect of indomethacin in the development of the postreperfusion syndrome during liver transplantation in pigs. PMID- 1871875 TI - Successful treatment of acute transplant renal vein thrombosis with selective streptokinase infusion. PMID- 1871876 TI - Anemia associated with pregnancy in a cyclosporine-treated renal allograft recipient. PMID- 1871877 TI - Ten questions to ask about revolving drug funds. AB - For any health financing scheme, the key issue is how to raise sufficient resources to provide a reasonable service when poverty means that many people are unable to afford such a service. A revolving drug fund is a scheme where drugs are sold at cost-price, plus a mark-up, and the revenue is used to replenish the drug stocks. Probably the most difficult part of establishing an RDF is setting prices. There should be sufficient mark-up to cover exempt treatments, transport costs, inflation and currency devaluations. Adequate records must be kept. If the amount of money and/or drugs in the RDF appears to be declining, the reason can be established. RDFs should not be seen in isolation from other considerations of the health care system. Drugs should not be sold without an adequate check on prescribing habits. Care should also be taken that the money-making potential of drugs does not distract from preventive activities. PMID- 1871878 TI - Chronic diarrhoea in adults in the tropics: a practical approach to management. PMID- 1871879 TI - Some unusual presentations of hepatic amoebiasis in Enugu, Nigeria. AB - Eighty-two cases of hepatic amoebiasis were diagnosed and treated at the University of Nigeria Teaching Hospital during a 4-year period. Typical or classical features were observed in 75 (91.4%) of the cases while the remaining seven presented atypically or unusually. These were obstructive jaundice (three cases), coma (two cases) and pyrexia of unknown origin (two cases). All the cases had positive gel diffusion precipitation test for amoebic antibodies, and in all but one there was demonstration of an abscess cavity. In the three cases of obstructive jaundice, the abscess cavities were located close to the hilum and compressed the main bile duct. There was no mortality recorded especially in the jaundiced cases despite the grave prognosis associated with jaundice in hepatic amoebiasis. This study demonstrates the need to consider hepatic amoebiasis in an area when patients present with either obstructive jaundice, coma or pyrexia of unknown origin and to do ultrasonography as an initial investigation in such patients. PMID- 1871880 TI - Chronic osteomyelitis in children in Bulawayo, Zimbabwe. PMID- 1871881 TI - Design of an easy-to-read ICU-chart. PMID- 1871882 TI - A nasty knock on the head: reflections from a district hospital. PMID- 1871883 TI - Use of physiotherapy records to monitor the efficacy of a poliomyelitis vaccination programme in Ilorin, Nigeria 1981-1988. AB - During the 8 years of a poliomyelitis control programme in Ilorin Local Government Area, Nigeria, a maximum of 85% of children aged 12-23 months were estimated to have received three doses of trivalent oral polio vaccine (TOPV). The estimated incidence of paralytic poliomyelitis decreased by 65%, suggesting a low vaccine efficacy of approximately 76% for the currently used TOPV. A more detailed study of TOPV efficacy (eg case control or cohort study) is required, however, to provide a more accurate estimate. Similar low-cost efforts at documenting the impact of TOPV on the incidence of poliomyelitis, using physiotherapy clinics as independent sentinels, are needed from many other centres. To increase the efficacy of the primary series of TOPV in Nigeria, the number of doses constituting the primary series should be increased to four (including one at birth), as recommended by the World Health Organization. PMID- 1871884 TI - Balanced participation in development. PMID- 1871885 TI - Community participation in health care: who participates with whom? PMID- 1871886 TI - Malaria and asthma. PMID- 1871887 TI - Antivenom treatment for scorpion stings. PMID- 1871888 TI - Organophosphate poisoning: diagnosis and treatment. PMID- 1871889 TI - Infertility and onchocerciasis. PMID- 1871890 TI - A case of concomitant intra- and extra-uterine pregnancy with successful outcome. PMID- 1871891 TI - Diagnosis of lower respiratory infection. PMID- 1871892 TI - Sero-surveillance of HIV infection in the red-light areas of Sangli district. PMID- 1871893 TI - Peribulbar blockade for eye surgery. PMID- 1871894 TI - Simple methods for the removal of non-deflating balloon bladder catheters suitable for the developing countries. PMID- 1871895 TI - The Taylor pressure reducer in cataract surgery. AB - A retrospective study was undertaken to determine whether the use of the Taylor pressure reducer during routine intracapsular cataract surgery lowered the incidence of vitreous loss. A significant reduction in the vitreous loss rate was noted. The Taylor pressure reducer is a useful device for the prevention of this complication in the Third World. PMID- 1871896 TI - A simple sternum-lifting retractor for vagotomy. PMID- 1871897 TI - Should children with typhoid peritonitis be operated on? PMID- 1871898 TI - Ultrastructural study of mitochondria in oncocytes. AB - A number of mitochondria in oncocytes show pleomorphism by conventional electron microscopy. In an investigation of their stereostructure, specimens were obtained from 11 patients with Warthin's tumor, parts of which were used in the preparation of serial thin sections. It was revealed that cup-shaped and concentric ring forms of mitochondria resulted from invagination and that aberrant cristae such as the sheaflike and vesicular types were both derived from laminated cristae with vesicular structure. PMID- 1871899 TI - Ultrastructural morphology of folliculo-stellate cells in human pituitary adenomas. AB - Fifty-six pituitary adenomas were studied by electron microscopy in a search for the presence of folliculo-stellate cells (FSCs) with the aim of evaluating their prevalence and ultrastructural morphology. FSCs were scattered in two adenomas (one oncocytoma and one densely granulated GH cell adenoma) and were numerous in a sparsely granulated GH cell adenoma; their overall prevalence was 5.4%. Ultrastructural examination of the three neoplasms revealed that FSCs were hypertrophic element with abundant cytoplasm and organelles (in contrast to FSCs of the normal pituitary) and no obvious signs of neoplastic transformation. Junctional complexes between FSCs were similar to those described in the normal gland. Numerous follicular structures were lined by FSCs. FSCs in pituitary adenomas are probably nonneoplastic, reactive cells showing signs of hyperactivity, similar to FSCs found during pituitary hypersecretion and in estrogen-induced tumor. PMID- 1871900 TI - Malignant enterochromaffinlike cell carcinoid of the gastric stump: an ultrastructural study. AB - A metastasizing carcinoid of the gastric stump found 25 years after Billroth II gastric resection for duodenal ulcer is described. Electron microscopy and optical endocrine cell staining proved the tumor to be composed of enterochromaffinlike (ECL) cells. This unusual combination further shows that, at variance with most of these tumors, ECL cell carcinoids may develop also in a condition excluding a trophic effect of gastrin. This case emphasizes the malignant behavior of gastrin-independent ECL cell tumors. PMID- 1871901 TI - Nondifferentiated-type small cell sarcoma of kidney in a young woman. AB - A case of rapidly fatal small cell sarcoma of kidney in a young woman is described. Histologic, immunohistochemical, and ultrastructural studies demonstrated some features not reported previously in the literature, such as the arrangement of vimentin intermediate filaments in small irregular masses and the presence of various types of cytoplasmic projections. These findings, together with the observation of rare neoplastic elements with immunophenotypic and subcellular aspects of histiocytic and myofibroblastic differentiation, suggest that this tumor should be included in a group of small cell sarcomas of kidney lacking features of differentiation and should be considered a new variant occurring in adulthood. PMID- 1871902 TI - An unusual malignant sarcoma of the omentum with extensive intraperitoneal metastases and small bowel obstruction. PMID- 1871903 TI - Case for the panel. Cytoplasmic structures in the cells of esophageal squamous cell carcinomas. PMID- 1871904 TI - Unusual pigmented vesical lesion in a middle-aged woman. PMID- 1871905 TI - Characterization of tumor-infiltrating mononuclear cells in renal cell cancer: quantitative analysis by immunoperoxidase staining. AB - In order to determine whether tumor-infiltrating mononuclear cells (TIM) of renal cell cancer (RCC) is suitable for adoptive immunotherapy, their number and characteristics were examined immunohistologically. TIM consisted of T cells and a smaller number of macrophages. Among T cells, CD8-positive cells were the dominant population which was reported to be more potent for the lysis of tumor cells. The number of T cells was variable: in 5 tumors no T cells were observed and in an other 5 the number of T cells were less than 2 x 10(6) cells/cm3. These results suggest that the TIM of RCC might be favorable for adoptive immunotherapy but TIM could not be available in some cases because of their small number. PMID- 1871906 TI - Extracorporeal shock-wave lithotripsy for small symptomatic renal calculi: is it effective? AB - Renal calculi with a diameter of less than 5 mm can pass spontaneously. However, some patients have small symptomatic renal calculi for more than 3 months. We evaluated the results of extracorporeal shock-wave lithotripsy in 38 patients with such stones. Patients presented with loin pain, hematuria, infection, or a combination of complaints. Average stone size was 18 mm2. After a wait of 3 months for spontaneous evacuation without success, all patients were treated with a Siemens Lithostar. Three months after treatment, 19 patients (50%) were completely free of stones, but 7 still had complaints; of the 19 patients with residual fragments, 8 (42%) were free of complaints. Both evacuation and resolution of complaints were achieved in only 12 of the 38 patients (32%). We conclude that one should be reluctant to treat small renal calculi, because spontaneous evacuation occurs in about 80% and the results of treatment are restricted. PMID- 1871907 TI - Electrohydraulic and ultrasonic lithotripsy in 100 consecutive cases of primary ureteral stones. AB - We have performed, between May 1985 and December 1988, in situ lithotripsy in 100 consecutive cases of primary ureteral stones, using electrohydraulic lithotripsy in 33 patients and ultrasonic lithotripsy in the remaining 67. After using similar instruments and surgical techniques in both groups, we have comparatively evaluated the complications encountered and the results obtained. With the electrohydraulic lithotripsy we have obtained a complication rate of 42% (operative and postoperative) and favorable results in 72.7% of the patients; using ultrasonic lithotripsy, the complication rate was 10.4%, and favorable results were obtained in 92.5%. We conclude that, at least in our experience, ultrasonic lithotripsy is less invasive and more successful than electrohydraulic lithotripsy in the treatment of primary stone disease. PMID- 1871908 TI - Static and dynamic radionuclide imaging in the diagnosis of the acute scrotum. AB - In the acute scrotum, diagnosis can be difficult in certain cases. In 107 patients the value of static and dynamic radionuclide imaging was evaluated. Static images provide a sensitivity and reliability of over 90%. Quantitative measurements do not give additional information in the differential diagnosis of these patients. Generally, scintigraphy can only be advocated if available as an emergency procedure. It is not necessary in cases with clinically obvious diagnosis of acute testicular torsion or epididymitis, but can be very helpful and reliable in unclear cases, i.e. for the evaluation of testicular perfusion after scrotal trauma. PMID- 1871909 TI - Effects of hypogastric nerve and sympathetic chain stimulation on the pelvic nerve induced penile erection in the dog. AB - The effects of electrical stimulation of hypogastric nerve and sympathetic chain on 'electroerection' (penile erection induced by electrical stimulation of the pelvic nerve) were studied in dogs to clarify the physiological roles that these neural inputs may play in producing and/or maintaining penile erection. As an objective parameter of hemodynamics of the penile circulation, the pressure in the corpus cavernosum of the penis was measured. Hypogastric nerve electrostimulation was performed in 24 dogs who had received pelvic nerve stimulation and, therefore, had 'electroerection'. Ten dogs responded to this procedure with an augmentation of 'electroerection', 10 with an attenuation of 'electroerection', and 4 with no appreciable changes. 4 out of the 10 animals who exhibited an attenuation response were then given an alpha 1-adrenergic blocker (prazosin hydrochloride) prior to the electrical stimulation to evaluate the specificity of the effects of the hypogastric nerve stimulation. In 3 of the 4 dogs the attenuation effect was abolished by this treatment and instead an augmentation effect became evident. Sympathetic chain electrostimulation was performed in 6 dogs with 'electroerection'. When applied to the L4-5 interganglionic segment, it produced a biphasic response which consisted of an initial increase followed by a decrease of the intracorporeal pressure. In contrast, stimulation of the L2-3 interganglionic segment produced a monophasic response consisting of only augmentation of the intracorporeal pressure. These data suggested that there might be two groups of fibers in the hypogastric nerve and sympathetic chain which are functioning antagonistically, and that the anti erectile neural inputs are mediated primarily by the alpha 1-adrenergic system. To examine the sites of penile vasculature where the innervating hypogastric nerve exerts its effects, electrical pelvic/hypogastric nerve stimulations were performed in dogs in whom the inflow blood circulation to the corpora cavernosa was disrupted by arterial ligation and replaced by a constant saline infusion. It appears that the stimulatory input via the hypogastric nerve caused an increased blood flow into the cavernous space due to vasodilation of the inflow blood vessels, and the inhibitory effect occurred mainly due to relaxation of the draining blood vessels with a resultant increase of the blood outflow from the cavernous space. PMID- 1871910 TI - Implantation of the urethral stent for treatment of complex urethral strictures. Evaluation of the functional and radiological results. AB - We describe the results after implantation of a urethral stent in 6 patients with recurrent urethral strictures. Four patients had strictures located in close vicinity to the external sphincter. In 3 of these 4 patients open urethroplasty procedures had failed. The treatment was successful in 5 of the 6 patients with a follow-up of 6-10 months. However, in 1 patient who had a complex stricture close to the sphincter, dense fibrotic strictures recurred at the proximal end of the stent where a short segment of the stricture was left uncovered in order to preserve continence. We conclude that implantation of the stent is a valuable treatment for complex strictures in the vicinity of the sphincter on condition that the stent covers the whole stricture. PMID- 1871911 TI - Use of testosterone ointment before hypospadias repair. AB - Fifteen children, aged between 2 and 9 years old, with hypospadias (4 penile; 6 penoscrotal; 3 scrotal; 1 perineal) were administered testosterone ointment before one-stage urethroplasty. Temporary penile growth and skin enlargement were obtained in all. Side effects were negligible. The plasma testosterone level was measured before, during and after testosterone administration. During testosterone stimulation, the plasma testosterone level ranged from 30 to 190 ng/dl, and returned to the normal range a week after administration had been stopped. Primary success of hypospadias repair was obtained in 10 of 15 children (66.7%). PMID- 1871912 TI - Preoperative oral and postoperative parenteral antibiotic prophylaxis of wound infection in total cystectomy with ileal urinary diversion. AB - We describe an investigation of postoperative abdominal infectious complications and discuss two regimens for preoperative antibiotic bowel preparation in cases who underwent total cystectomy with ileal urinary diversion. Ten cases (28.6%) of 35 who had been operated developed abdominal infectious complications. Six showed abdominal wound infection, 2 showed intrapelvic abscess and 2 showed abdominal wound infection with intrapelvic abscess. Of the 19 strains of organisms isolated from the postoperative infections, 11 (57.9%) were anaerobic bacteria and the most commonly isolated bacteria was Bacteroides. A significantly lower incidence of postoperative infection was found in cases who had received tobramycin and vancomycin (0%) than in those who had received kanamycin alone (41.7%). These results indicate that anaerobic bacteria are the major contributors to postoperative infections following total cystectomy with ileal urinary diversion and that tobramycin-vancomycin prophylaxis greatly reduces the incidence of postoperative infections. PMID- 1871913 TI - Bursting strength of the rat aorta: comparison of suture and laser anastomoses. AB - The bursting strength of sutured and laser-welded vascular anastomoses were assessed in a rat aorta model. Postoperative investigations included postmortems, light and scanning electron microscopy and measurements of bursting strength at set intervals (30 min, 3, 14 and 28 days postoperatively, p.o.). Laser-bonded anastomoses consistently demonstrated lower bursting strengths than suture controls, with statistically significant differences at 30 min and 3 days p.o. (p less than 0.01). Laser anastomosis was easier and faster to perform, the foreign body reaction was markedly lower than in sutured controls. Formation of aneurysms was not observed. PMID- 1871914 TI - Young's syndrome: report of two Japanese cases. AB - Young's syndrome is characterized by azoospermia due to bilateral epididymal obstruction associated with chronic sinobronchial disease. We report two Japanese cases of Young's syndrome who were treated with microsurgical epididymovasostomy. The histopathology of the caput epididymis showed an obstruction at the most distal region of the ductuli efferentes. The incidence of Young's syndrome in patients with obstructive azoospermia was much lower for mongoloids than for Caucasians. PMID- 1871915 TI - Prognostic relevance of DNA ploidy and proliferative activity in urothelial carcinoma of the renal pelvis and ureter. A study on a follow-up period of 6 years. AB - In 55 patients with urothelial carcinoma of the renal pelvis or ureter, the ploidy, the DNA heterogeneity and the counts of cell cycle phases in the tumor were examined by means of single-cell DNA cytophotometry in order to find more prognostic factors than those already known (stage and grade). Follow-up periods ranged from 1 to 6 years. At the time of first diagnosis, 42 (76%) of the patients had tumors of the renal pelvis, 13 (24%) of them had ureteral tumors. 23 (42%) patients were in stage pT 1 N 0, 15 (27%) in stage pT 2 N 0, 12 (22%) in stage pT 3 N 0, and 5 (9%) were in stage pT 3 N+. The histological malignancy grade most frequently seen in the patients examined--i.e. in 51% of cases--was malignancy grade II. 25% of the patients had grade III tumors whereas only 24% had grade I tumors. With malignancy grade I, DNA cytophotometry showed DNA frequency peaks to be in the diploid range while tumors with malignancy grade II showed heterogenous DNA patterns. 71% of the patients with malignancy grade III showed aneuploid DNA values; 29% of them had polyploid DNA values. For malignancy grades II and III, the proliferation rate of the tumor cells was statistically significantly higher than for malignancy grade I. The determination of tumor heterogeneity and tumor cell proliferation by means of DNA cytophotometry gives valuable clues regarding prognosis. PMID- 1871916 TI - [The indices of cell membrane destabilization in urolithiasis patients]. AB - The paper gives the results of a clinical and biochemical study of 165 patients with urolithiasis and 46 healthy persons. Their urinary samples and renal biopsy specimens were analysed to assess the structural and functional status of nephron cell membranes. In urolithiasis patients, the urine was found to contain a great quantities of emulsified lipids enriched in toxic phospholipid and cholesterol metabolism products; renal tissue cytomembranes in the patients were depleted of phospholipids, free cholesterol and enriched in phospholipid lysoforms and cholesterol esters. Lipid phase destabilization of nephron epithelial membranes was shown to be pathogenetically associated with concrement formation. The examination of emulsified urinary lipids is an objective tool of renal tissue crystallization activity and may be recommended for the early diagnosis of urolithiasis, as well as an indicator of membrane-stabilizing therapy efficiency. PMID- 1871917 TI - [Combinations of different types and variants of ectopia of the ureteral ostia]. AB - Ectopias of the ostia ureteris are generally accepted to be divided into intra- and extravesical ones. It is expedient to divide this abnormality into lower (that of the ureteral ostium below and more medial than the normal site) and upper (that of above and more lateral than the normal site) ectopias of the ostia ureteris. The lower ectopia may be intra- and extravesical. The upper ectopia may be also intra- and extravesical. In ureteral ostial ectopia, the passage of urine from the kidney into the urinary bladder is impaired due to either mechanical ureteral obstruction or vesicoureteral reflux. The lower intravesical ectopia of the ostium ureteris is frequently associated with ureterocele. The study was undertaken to examine 242 patients with ectopia of the ostia ureteris, including those with extravesical (5.3%), intravesical (93.8%) and associated (0.9%) ectopias. Lower ectopia of the ostia ureteris was observed in 28.5%, upper, in 64.5%, and associated ones in 7%. The authors outline 14 different combinations of various types and variants of ureteral ostial ectopias which were observed in 25 patients. The diagnosis of such complicated abnormalities may be made only on the basis of knowledge of all the variants of lower and upper ectopias of the ostia ureteris. All these abnormalities require surgical correction. PMID- 1871918 TI - [The chemotherapy of patients with prostatic tuberculosis]. AB - The authors examined the efficacy of various chemotherapeutic regimes in the management of patients with tuberculosis of the prostate. The data of bacteriostatic secretion activity of the prostate showed that the most effective regimes were as follows: 1) isoniazid and ethambutol followed by galvanization of the prostatic region, then rifampicin suppository containing dimexid; 2) isoniazid and rifampicin suppository containing dimexid; oral ethambutol. Proper curative measures depending on the clinicomorphological types of the tuberculous prostate and their duration are also given. Using the proposed regimes in 68 patients provided 80.7-96.6% positive responses. The authors advise to carry out seasonal courses of chemotherapy using mainly the method of rectal administration of anti-tuberculous agents, dimexid and tissue electrophoresis. PMID- 1871919 TI - [Enteroplasty in bladder tumors]. AB - A total of 429 patients with urinary tumors have been operated on in the past 10 years, 80 of them have been undergone cystectomy. Intestinal plasty of the urinary bladder was performed in 38 patients. These one-stage operations in 15 patients yielded a high postoperative mortality rate (33.3%). Two-stage surgeries in 23 patients largely reduced mortality (8.9%). The authors provide recommendations how to conduct the two-stage surgery and limited indications for one-stage interventions. PMID- 1871920 TI - [The dispensary care and work disability expertise of bladder cancer patients following cystectomy]. AB - A question of the principles and methods of medical prophylactic survey in patients with bladder cancer who have undergone cystectomy with subsequent ureterosigmoid anastomosis and ureterocutaneostomy is not currently developed. On a basis of 79 follow-ups of patients with bladder cancer after cystectomy, a procedure of prophylactic survey in the setting of regional oncologic dispensary and district polyclinic was worked out. It is stressed that it is necessary to follow up the patients for a possible relapse and metastasis development as well as complications of the upper urinary tract and kidneys and metabolic shifts (acidosis, dyselectrolytemia). From this viewpoint we propose a scope of essential examinations during the medical prophylactic survey. Our results of the patients follow-ups after cystectomy are also given. Recommendations for the patients working ability estimation are proposed and it is noted that the estimation is to be carried out on a strictly individual basis because the patient's rehabilitation depends on many factors. But the main principles of such patients' working ability estimation are submitted in schemes of a working ability examination. They depend on the stage of the process and on the method of urine drainage after cystectomy. PMID- 1871921 TI - [The prevention and treatment of complications from extracorporeal lithotripsy]. AB - Since October 1987, remote lithotripsy (RL) has been performed at the Research Institute of Urology, RSFSR Ministry of Health, over 3 years. "Specific" complications associated with RL made with a Urat-P lithotriptor are common in the immediate period following the procedure. The paper describes the analysis and outlines complications, causes of their occurrence, and prophylactic measures. A total of 2,300 lithotripsies conducted in 1988-1990 were analyzed. The incidence of the complications was 2.4%, which is similar to the values observed with foreign lithotriptors. The occurrence of acute pyelonephritis caused by RL is likely to increase when there is a baseline active inflammatory process in the urinary tract. The paper proposes a procedure for selecting patients in RL, antibacterial preoperative therapy, methods for lithoclasty with the use of the national lithotriptor. Involving two lithotripsy regimens. The authors find it necessary to drain the urinary tract within the first days of the appearance of signs of acute pyelonephritis by renal catheterization or paracentetic nephrostomy. PMID- 1871922 TI - [The x-ray endovascular treatment of renin-dependent arterial hypertension with secondary aldosteronism in patients without vasorenal involvement]. AB - In 20% of cases, essential hypertension is of high renin pathogenesis which is indifferent of that of renal lesions. In these patients high blood pressure is closely related to high aldosterone generation due to elevated angiotensin II levels. Adrenal blood portalization is a possible way of abolishing secondary aldosteronism and hyperreninemia in this case. With this, 90-98% aldosterone and 20-30% renin are inactivated, which served as the basis for bilateral electrocoagulation of adrenal central veins in 13 patients with permanent and malignant arterial hypertension. The renin-dependent pattern of essential hypertension was confirmed by a positive BP response to a tested captopril dose (25 mg), the vasorenal one was ruled out on the basis of the peripheral captopril test, captopril pharmacorenography. Bilateral electrocoagulation of adrenal central veins was performed during a phlebographic examination. The manipulation proved to be successful on 11 (85%) left and 9 (70%) right adrenals. Blood pressure became lower in the first day and stable on days 4-5. There was a significant decrease in blood pressure at a year follow-up, in increased aldosterone levels, plasma renin activity with unchanged adrenocorticotropic hormone concentrations. After the manipulation, 2 patients refused to take antihypertensive drugs, 11 patients received lower doses of drugs. The method for abolishing secondary aldosteronism is considered to be promising for further clinical studies. A special attention should be given to patients with diseases concomitant with essential hypertension who have no alternative to surgical treatment. PMID- 1871923 TI - [The treatment of severe arterial hypertension in patients with chronic kidney failure with captopril and beta-adrenoblockaders]. AB - Twenty nine patients with chronic renal failure associated with severe essential hypertension, 10 of whom being on programmed hemodialysis, were treated with captopril, a converting enzyme inhibitor (n = 21) and sectral-400, a cardioselective beta-blocker (n = 11). Blood pressure (BP) changes and renin angiotensin-aldosterone system parameters were studied by radioimmunoassay. When given in a daily dose of 25 to 100 mg for a long time, captopril provided a good and satisfactory antihypertensive effect in 9 patients; a weak or no effect was achieved in 9 and 5 patients, respectively. BP lowered by an average of 14.7%. There were 72% and 17.9% increases in active and total renin levels, respectively, and a reduction in the proportion of inactive in total renin. With sectral-400, 400-1200 mg/day, good, weak or no effects were observed in 6, 3, and 2 patients, respectively. BP decreased by an average of 13%, there were 59% and 12% reductions in active and total renin levels, respectively, whereas the content of inactive renin showed a 21% increase, suggesting a diminution of renin synthesis and activation. The initially higher plasma aldosterone levels in most patients (by an average of 4.2 times) decreased significantly by 23% with the two drugs. Thus, in severe essential hypertension it is advisable to use blockers of the renin-angiotensin system in patients with chronic renal failure, captopril is particularly indicated in those who have a high renin activity, and the hyperkinetic syndrome is an additional indicator for sectral-400 use. PMID- 1871924 TI - [A comparative assessment of homeostasis and hemodynamics during the performance of bicarbonate and acetate hemodialysis]. AB - The article deals with the comparative analysis of certain values of homeostasis and hemodynamics in 25 patients with chronic renal failure who were subjected to systematic bicarbonate and acetate hemodialysis. Comparative study of some values of homeostasis, hemodynamics and myocardial contractility in patients with chronic renal failure during hemodialysis with acetate and bicarbonate solutions showed the advantages of bicarbonate hemodialysis. During bicarbonate hemodialysis, in addition to the patients' good tolerance to the procedure, the correction of the disturbed homeostasis was more physiological on the one hand, and positive shifts occurred in the activity of the blood circulatory system on the other. The study showed the expediency of using bicarbonate hemodialysis in patients with chronic renal failure with individual intolerance to acetate solution, and with severe heart failure and metabolic acidosis. PMID- 1871925 TI - [The level of neopterin in the plasma of patients with acute kidney failure during treatment with continuous arteriovenous hemofiltration]. AB - Neopterin is a biochemical marker of cellular mediated immune reactions and may be used in elucidating the cause of acute renal failure. 9 patients (6 males, 3 females) aged 23 to 56 years suffering from a severe form of the disease were examined. A continuous arteriovenous hemofiltration was used as a treatment with exchanging 29.2 +/- 2.0 (14-65) kg of fluid during 24 hours. The patients' diet included protein and amino acids of 1.2-1.5 g/kg of body weight, 35-45 Kcal/kg of body weight per 24 hours with meal and parenteral infusions. 4 patients died. Contents of neopterin in the plasma of the healthy equaled to 6.8 +/- 03 (3.4 11.3) nmol/l (radioimmunoassay; Henning; Berlin, GmbH). In patients with acute renal failure plasma neopterin contents were increased, i.e. 130.0 +/- +/- 9.6 (48.2-200.2) nmol/l and in two thirds of the cases and correlated with creatinine levels (r = + 0.60 +/- 0.17; p less than 0.05; n = 23), thus showing a simultaneous influence of anuria and continuous arteriovenous hemofiltration on a neopterin pool amount at the same time, in patients with tropical malaria and hemotransfusion shocks (2 cases), the neopterin contents were extremely high and did not correlate with the creatinine level. During continuous hemofiltration at a rate of 21.6 +/- 1.3 (15.9-36.9) ml/min neopterine clearance was 17.2 +/- 2.1 (6.7-36.2) ml/min. Neopterin hyperproduction after blood transfusion suggests an immune conflict as a possible cause of acute renal failure. PMID- 1871926 TI - [Interstitial nephritis in urological practice]. AB - The presented material consists of 9 postoperative patients' investigations. Interstitial nephritis was diagnosed in them after histological examination. Seven patients had a chronic disease, 2--acute disease. The revealed possible predisposing factors were: a prolonged use of analgetics, contact with formalin and typographical dyes, systematic alcohol usage, frequent catarrhal diseases with long-term fever, a history of acute renal destructive process. The clinical picture of patients with chronic interstitial nephritis was characterized by long periods of temperature elevation, small changes in blood counts, weakness, pain in the lumbar region. In urine analyses: moderate microhematuria, leukocyturia, proteinuria. There were signs of early damaged renal tubular functions. Antiinflammatory therapy was ineffective so the patients were operated on for various indications. During the operations there were severe macroscopic renal cirrhotic deteriorations. 2 patients underwent nephrectomy, 15 intraoperative biopsy. Histologically there were revealed: signs of interstitial tissue various cirrhotic changes in hydrops and lymphoplasmacytic infiltration with tubular compression and dystrophic changes. The following complex therapy including nonsteroid antiinflammatory agents, in some cases corticosteroids, desensitizing and antihistaminic remedy allowed one to achieve alleviation of the process. PMID- 1871927 TI - [The treatment of urethral strictures]. AB - Analysis of the results of many-year treatment of 788 patients with traumatic urethral strictures indicated that it was advisable to perform Khol'tsov's operation without leaving a catheter in the urethra in short strictures of the anterior urethral segment, Solovov's operation was indicated for occlusive strictures of the posterior urethral portion, whereas endourethral interventions (urethrotomy, resection) were beneficial in short patent strictures. Vesicourethral strictures required transurethral electroresection. Stenotic urethral changes were seen at different levels in 3.7% of postoperative patients. Some recommendations were proposed by the authors for prevention of the changes. A classification of urethral strictures was also presented. PMID- 1871928 TI - [Morphological changes in the stenotic distal portion of the urethra in girls]. AB - Morphological changes were examined in the distal urethra with its stenosis in 40 girls aged under 10 years. Intraoperative (urethromeatotomy) biopsy specimens were taken via a wedge cut made in the inferior meatal wall. The specimens were stained with hematoxylin and eosin, as well as with picrofuxin by the van Gieson method. Histological investigations showed that during urethral stenosis, the underlying pathological process in 35 patients was chronic urethritis with extended leukocyte infiltration onto the mucosal and submucosal layers. Leukocyte infiltration was diffuse in 14 girls, whereas in 21 it was focal to form microabscesses in some cases. In addition, the submucosal layer of the distal urethra displayed vegetations of the connective tissue that had been sclerosing. The frequency of abundant vegetations in the connective tissue, its fibrosis and sclerosis increased in relation to a history of the disease, which corresponded to the age of children in most cases. The distal urethral stenoses were classified as acquired narrowings of inflammatory genesis. In 5 patients, the mucosal and submucosal layers underwent no inflammatory changes and their distal urethral stenoses were applied to congenital or hereditary ones. With irreversible sclerotic changes, urethromeatotomy along with disruption of the fibrous annulus is one of the major tools for treating distal urethral stenosis. PMID- 1871929 TI - [Priapism in a patient with acute glomerulonephritis]. PMID- 1871930 TI - [The nature of the homeostatic changes in nephrolithiasis patients]. AB - Rheorenographic findings, activities of 4 major glycolytic enzymes and 3 Krebs cycle ones in serum and blood, urinary fibrinolytic activity were analyzed in 117 patients with coral nephrolithiasis (the pelvis was drained after calculus removal) in 114 patients with non-coral calculi (the pelvis was sutured) before and 7, 14 days after surgery. Rheography revealed a significant decrease in arterial vascular tone and blood filling and an impairment in venous return in the diseased kidney. In the patients with nephrolithiasis, the enzymatic activity showed 3.5-10.5- and 4.5-11.5-fold increase (p less than 0.001) in the Krebs cycle and glycolysis, respectively, suggesting activation of not only oxidative phosphorylation, but anaerobic glycolysis. Tubular metabolic acidosis occurred, which made the enzymes enter blood and urine from the epithelial cells. On days 7 14 of postoperation, rheographic parameters, enzymatic and fibrinolytic activities of the urine remained virtually unchanged as compared to the values observed in the preoperative period. Moreover, the patients with a sutured pelvis showed highly accelerated glycolysis during the surgery against prior to the procedure. Urinary mitochondrial enzyme release increased, which reflected an enhancement of degenerative changes in nephron cells. Urinary fibrinolytic activity remained lower. In the patients with a drained pelvis, all the parameters in question became better. PMID- 1871931 TI - [Nuclear medicine examination procedures in urology. Part 1]. PMID- 1871932 TI - [TNM-oriented therapy planning in bladder cancer]. AB - The standard diagnostic procedures for bladder carcinoma include transurethral resection, bimanual palpation of the bladder under general anaesthesia, ultrasound examination and CT scan of the abdominal and pelvic regions. An IVP is additionally carried out for the detection of concomitant upper urinary tract tumours. Preoperative urinary cytology is also performed, as in 10% of all patients the degree of malignancy of bladder cancer according to the TNM system is revealed more exactly by cytology than by histology. New computerized examination techniques have been designed in attempts to improve the accuracy of the diagnostic process. Therapeutic modalities according to the classification of bladder carcinoma in the TNM system have to be based on the different efficacies of the diagnostic procedure: In superficial low-grade tumours the diagnostic efficacy is quite high, so that transurethral resection remains the treatment of choice. Superficial high-grade tumours are attended by reduced 5-year survival rates, and patients with such tumours must therefore be regarded as a high-risk group. In muscle-invasive bladder carcinoma reduced diagnostic efficacy and unsatisfactory treatment results are seen, so that in this condition cystectomy at an early stage is indicated. PMID- 1871933 TI - [Use of photodynamic therapy in the treatment of refractory carcinoma in situ]. AB - Photodynamic therapy (PDT) is a new and innovative approach to the treatment of malignant disease. This treatment modality involves administration of a photosensitizer, which is retained in malignant tissue, followed by exposure of that tissue to light corresponding to one of the absorption bands of the drug, with resultant cell death. Several photosensitizers are currently under study, but haematoporphyrin derivative (HPD) is the drug that has been used almost exclusively in clinical urological trials. Both direct and indirect methods have been used to document the preferential concentration or retention of HPD in malignant urothelium. Although this drug is not a perfect tumour localization aid, it is perhaps the best that has thus far been studied for transitional cell carcinoma of the bladder. Over the past decade of investigation, PDT has become established to the point that it is now being tested in phase II and III trials against standard and approved drugs for the treatment of noninvasive transitional cell carcinoma of the bladder. PMID- 1871934 TI - [Carcinoma in situ of the urinary bladder--definition and status of treatment]. AB - Carcinoma in situ is a noninvasive intraepithelial disease without papillary growth. Anaplasia and a disarranged growth form of the epithelium are histopathological characteristics. Carcinoma in situ can appear as a secondary disease combined with a papillary tumour or after transurethral resection of a papillary tumour. On the other hand, primary carcinoma in situ is also known to appear without a papillary tumour. Symptoms of cystitis are often seen. Sometimes, however, the disease does not cause any symptoms. Urinary cytology is the most important noninvasive investigation, followed by biopsy of the bladder epithelium. Treatments commonly applied at present are intravesical immunotherapy with BCG and intravesical chemotherapy. Photodynamic laser therapy is presently being investigated. Carcinoma in situ is very significant as a prognostic factor. The progression rate is up to 83%, and progression signifies development of a poorly differentiated invasive bladder cancer. The treatment of choice for inefficiently treated carcinoma in situ is cystectomy. The urinary diversion selected in men depends on the histopathological findings in the prostatic urethra; an ileum neobladder, the standard diversion in men, cannot be performed if carcinoma in situ has been found in the prostatic urethra. PMID- 1871935 TI - [Molecular biology studies of bladder cancer]. AB - The mechanisms that control the biological behaviour of urothelial cancer are complex, and many regulative interactions are involved. So far, few aspects of these control mechanisms have been recognized and characterized. A precondition for better understanding is knowledge the interaction of this factors. Some markers (e.g., chromosomal aberrations, EGFR expression) are correlated with progression of tumour. Whether they are the cause or the result of the aggressive behaviour of growth remains unknown. Only a few markers, especially in flow cytometry, will have any benefit in clinical routine. Whether it is possible to find a marker with prognostic value remains uncertain. PMID- 1871936 TI - [Animal experiment aspects of bladder cancer]. AB - Many aspects of bladder cancer remain obscure under clinical conditions. The natural course of the illness is seldom known in human patients, in whom only the treated natural history is subject to investigation. Cancer research in animals can complement clinical investigations. The following experimental set-ups are of importance; chemically induced bladder cancer; transplantation of human urothelial carcinoma in immunodeficient nude mice (xenograft model); transplantation of clinically induced bladder cancer in syngenetic animals (syngenetic model). These models are used for tumour induction and the development of immunotherapy, chemotherapy and new techniques. The extrapolation of these experimental results to clinical situations is being discussed. Some experimental results are of interest for practising urologists, e.g. increased incidence of tumour development in dilated upper urinary tract or in the bowel segment after urinary diversion; new therapeutic approaches such as breakdown of multidrug resistance to chemotherapy or administration of photodynamic therapy; planning of intravesical therapy relating to aspects of cell proliferation. PMID- 1871937 TI - [Familial adult cystic kidneys and malignant teratomas after kidney transplantation with cyclosporin therapy]. AB - We report on two brothers with adult polycystic kidney disease, malignant teratomas and other genital malformations. Because of the unusual accumulation of malformations of embryologically related organs, we postulate a connection between malformations of the kidneys and the genital tract, on the one hand, and teratomas on the other. No genetic coherence is known so far. It is unlikely that immunosuppression with cyclosporin after transplantation had caused these tumours. PMID- 1871938 TI - [Injuries of the pelvis and retroperitoneal organs]. AB - About 50% of all patients with pelvic fractures present with associated injuries. Diagnostic and therapeutic guidelines follow the step-by-step regimen used in polytraumatized patients. Whereas lifesaving emergency operations are rarely necessary, most associated injuries are operated on after completion of the first diagnostic phase in order to preserve organ function. Injuries of the pancreaticoduodenal system and ruptures of the digestive tract are particularly difficult to diagnose. Stabilization of pelvic fractures will take place in the phase of delayed reconstruction, usually several days after the accident. PMID- 1871939 TI - [Percutaneous sclerosing of kidney cysts with alcohol]. AB - Symptomatic benign renal cysts in 23 patients were obliterated by ultrasound guided puncture and instillation of sterile 95% ethanol. In no case did complications occur. In 5 cases the cysts recurred after an average of 3 months; the primary size (diameter) was more than 10 cm in all of these. This simple technique seems to be a suitable treatment option for smaller cysts up to 10 cm because of its low complication rate and because no hospital admission is required. PMID- 1871940 TI - [The functional, augmented rectal bladder. Initial clinical experience with 10 patients]. AB - From August 1988 until March 1990, 10 female patients received an augmented, functional rectal bladder, according to the technique first described by Kock. Indications were a radical cystectomy in 8 and a rediversion from a previously wet stoma in 2 patients. There was no perioperative mortality. Postoperative complications were obstructive pyelonephritis (1 case, treated with a temporary nephrostomy), obstruction at the ileal intussusception (1 case; operative revision) and slipping at the sigmoid nipple (1; no treatment). Intravenous pyelography 2-3 months postoperatively showed 13 normal and 5 slightly dilated renal units. All patients are completely continent by day, 7 are continent by night, 2 wear sanitary pads during sleep due to occasional spotting. Preliminary experience with this new technique is encouraging and warrants further clinical application in patients in whom the external urethral sphincter is not available to provide the continence mechanism. PMID- 1871941 TI - [Local hyperthermia in prostate cancer]. AB - We conducted a clinical trial evaluating the effects of hyperthermia in patients with carcinoma of the prostate, treating 20 patients with newly diagnosed carcinoma of the prostate with local microwave hyperthermia (915 MHz). Histological examination revealed hypoeremic effects and diffuse oedema with interstitial lymphoplasmatic cellular infiltration. However, necrotic tumour cells were not found in any of specimens. A second series consisted of 10 patients with metastasizing carcinoma of the prostate (n = 4 untreated; n = 6 hormone-resistant). For 8 weeks, epirubicin was administered once weekly, followed each time by local microwave hyperthermia 1 h later. The efficacy was evaluated according to the EORTC criteria. In 4 patients with untreated carcinoma no change was found in the size of the prostate or metastases. In 3 of the 6 patients with hormone-resistant carcinoma progressive disease was found, while the other 3 had stable disease. Only in 2 of the 10 patients did the grading of tumour regression reveal any improvement. Cytophotometric studies showed no change of DNA ploidy. Currently we consider hyperthermia unsuitable as monotherapy for carcinoma of the prostate, and the combination of epirubicin and hyperthermia is no more favourable than monotherapy with epirubicin alone. Further studies are necessary to evaluate other cytotoxic regimens and various patterns of application for hyperthermia. PMID- 1871942 TI - [Surgical correction of vesicovaginal fistulas with the Chassar Moir method]. AB - Besides a relatively high frequency of perioperative and postoperative dysfunctions of micturition, urogenital fistulae are the most frequent complication occurring after surgical gynaecological interventions. Vesico vaginal fistulae are the most common communication between the efferent urinary passages and the genital tract. From 1967 to 1987, 42 women who had developed a vesico-vaginal fistula after abdominal or vaginal surgery or irradiation were operated on again. Upon admission, all 42 patients were subjected to surgical closure of the vesico-vaginal fistula according to the vaginal method of Chassar Moir. In 41 women (97.6%) continence was re-established by adequate closure. PMID- 1871943 TI - [Experience with ultrasound-guided ESWL]. AB - The ESWL treatment of gallstones has led to the development of ultrasound-guided lithotripters. The interdisciplinary use of these new ESWL systems by urologists, general surgeons and gastroenterologists means that different requirements have to be met. As a result of this development, ultrasound in urology is gaining even more significance. While ESWL treatment of renal calculi under ultrasound guidance has quickly become a routine method, the in situ treatment of ureteral calculi is much more problematic. In our study the validity of diagnostic ultrasound for the localization of ureteral stones was investigated. In an unselected preliminary series only 30% of ureteral calculi could be located by ultrasound. The success rates were 39% for distal stones and 16% for proximal calculi. The treatment results of renal calculi are on a par with those previously obtained under fluoroscopic guidance. Once exact localization is obtained by ultrasound, disintegration rates for ureteral calculi are fully comparable to those performed under fluoroscopic guidance. However, 60% of ureteral stones can not be located by ultrasound. Therefore, retrograde manipulation and ureteroscopic stone disintegration gains more importance in interdisciplinary shock wave centers equipped with ultrasound-guided machines. A real alternative to second-generation lithotripters in the treatment of ureteral stones will thus only be obtained if an X-ray device can be added to the locating system if necessary. With this combination device the treatment of most ureteral calculi will thus be possible. PMID- 1871944 TI - [The "TUR catheter", a new indwelling catheter for postoperative bladder irrigation]. AB - A new catheter has been developed for bladder drainage following operations on the prostate or bladder. Instead of having 1 to 3 large holes at the tip, as in common catheters, it has 32 drainage holes, each 1.5 mm in diameter. Thus, unhindered drainage of the bladder is guaranteed even if the majority of the holes is obstructed. PMID- 1871945 TI - [Disorders of lipid metabolism and insurance medicine practice]. AB - The evaluation of lipometabolic disorders is presented within the framework of epidemiological and pathophysiological findings. Insurance medicine can base its risk assessment practices on the recommendations of American and European consensus conferences. The upper normal value for total cholesterol is in the vicinity of 200 mg/dl. The atherogenic risk of an elevated total cholesterol level can be further defined by determining the LDL and HDL cholesterol. The LDL cholesterol level should not exceed 160 mg/dl and the HDL level should not be lower than 35 mg/dl for men and 45 mg/dl for women. The quotients from the total/HDL cholesterol levels (normal value less than 6) and the LDL/HDL levels (normal value less than 4) can be used for differentiated risk assessment. Triglyceride levels exceeding 200 mg/dl are primarily to be taken into consideration as a risk indicator if there is a simultaneous reduction of HDL cholesterol. Additional parameters, such as nicotine abuse, hypertension, a family history of cardiovascular disease, impaired glucose tolerance, male sex, obesity and the existence of peripheral vascular disorders are also to be included in the risk profile. Determining additional lipometabolic substances is only of relevance to insurance medicine in individual cases. PMID- 1871946 TI - [Cardiac effects of a reducing diet]. AB - 40 in-patients have been treated by modified fasting during 4 weeks. Routine ECG's and radiological controls of heart size did not show signs of myocardial lesions or of an impairment of the generation, propagation or dissipation of cardiac impulse. Slightly elevated serum levels of CK, CK-MB, alpha-HBDH, SGOT, and SGPT could indicate a reduction of fat-free body-mass including some elements of myocardium. Potassium and magnesium levels should be controlled and sometimes corrected by ingestion of electrolyte preparations. Under the conditions described and with the methods we used, we could not demonstrate an increased cardiac risk during a weight reduction cure by modified fasting of moderate duration. This should also apply to low-calorie diets with a deficit of about 1000 cal./day, whilst total fasting and the substitution with protein preparations of poor nutritional value must be considered as risky procedures. PMID- 1871948 TI - [Surgical myocardial revascularization: indications, perioperative risk constellation and prognosis]. AB - Since the inception of coronary artery bypass grafting, refinements in surgical technique, myocardial preservation, anesthesia and in pre- and postoperative care, reduced the perioperative mortality and improved the long-term results in patients with chronic coronary artery disease. Large-scale, multicentre randomized and a multitude of non-randomized clinical trials of surgical versus medical treatment have set therapeutic standards for quality and refined the indications for bypass surgery. In summary, these studies clearly indicate that surgery is superior to medical therapy in symptom relief, decreased antianginal drug use and improved exercise performance, but does not improve the likelihood of return to employment, non-fatal myocardial infarction prevalence or hospitalization rates. After surgery, survival is prolonged in those subsets of patients who are considered at high risk, i.e. patients with left main disease (greater than 70%), with two-vessel disease with severe left anterior descending artery stenosis or with three-vessel disease with signs of significant ischemia on exercise or left ventricular dysfunction present. Specific individual risk profiles during coronary artery surgery were evaluated by a multicentre retrospective analysis of 8363 patients (QuaDRA-study) documenting a significantly higher perioperative letality and incidence of postoperative complications (low output syndrome, infection, renal dysfunction, psychosyndrome) in the elderly (greater than 65 years). PMID- 1871947 TI - [Prognosis after transient ischemic attacks]. AB - Transient ischemic attacks (TIAs) are reversible neurological deficits due to cerebral ischemia in a vascular territory lasting less than 24 hours, usually less than one hour. The natural course of TIAs is variable. One third of the patients suffer from a subsequent completed stroke with lasting disability, one third of the patients continues to experience TIAs and in one third no further symptoms are encountered. TIAs are a warning symptom of a generalized vascular process, myocardial infarction being the most common cause of mortality and ischemic brain infarction being the most common cause of morbidity. Clinical parameters--besides age--seem to be of minor prognostic relevance. Vascular risk factors should be evaluated in all TIA patients; especially, a cardiac work up including 2D-echocardiography and an exercise stress test should be performed. Duplex sonography of craniocervical vessels shows atherosclerotic lesions in a considerable proportion of patients with TIA; however, localization of these lesions does not always correspond to clinical symptomatology. Some angiographic features are of prognostic relevance. Computed tomography (CT) and magnetic resonance imaging (MRI) show ischemic lesions in a considerable proportion of patients, which connects TIAs directly to ischemic brain infarcts. The extent and localization of these lesions are of some prognostic relevance. Blow flow studies on single photon emission computed tomography (SPECT) and studies of brain metabolism on positron emission tomography (PET) are abnormal in many TIA patients for prolonged periods and also have some prognostic impact. TIA patients probably are a heterogeneous group with a common symptom. A detailed diagnostic work-up may have implications on a more specific and efficient therapy. PMID- 1871949 TI - [Incidence of sudden heart arrest in mitral valve prolapse syndrome]. AB - Among 1500 consecutive forensic autopsy cases 4 cases of sudden cardiac death due to a mitral valve prolapse syndrome could be found. Postmortem diagnosis depends on severe macroskopic changes of the valve leaflets. According to literature there is no increased risk of sudden cardiac death in cases of "silent" mitral valve prolapse. Only in 2%-4% of all cases severe mitral regurgitation or leaflet thickening above 5 mm leads to an increased incidence of sudden cardiac death. The 4 presented cases belong to this subgroup. PMID- 1871950 TI - [Myocardial infarct and occupational accident]. AB - According to our knowledge to day the cause of a heart infarction is a stenosing atheromatosis of the coronary vessels or an associated coronary thrombosis. Here are described two cases with unusual precipitating factors of a heart infarction, one by an anaphylactic reaction caused by smallpox vaccination, the other case caused by a very intensive stress situation. As the basic condition in the two cases was accepted a coronary heart disease but the described events were considered by the author as the determinating concomitant cause for the social accident insurance in consequence of their intensity and acuteness. PMID- 1871951 TI - [Athletic accident and insurance]. AB - While working-time has been reduced, time spent for leisure is growing and sports also get more important. This can be remarked in media as well as in different domaines of economy. Risks, concluded with sports are as different as the people who are affected by such risks. Legal insurance cover in the domain of sports is just partly given, hence it is much more advisable to effect a private insurance. PMID- 1871952 TI - Seroepidemiology of Bivens Arm virus infections of cattle in Florida, St. Croix and Puerto Rico. AB - Bivens Arm virus (BAV) is a newly discovered rhabdovirus infecting cattle and water buffalo in Florida. The virus is classified as a member of the Tibrogargan group, members of which have hitherto been found only in Australasia. They are considered to be transmitted by Culicoides species. Bivens Arm virus was first isolated from Culicoides insignis which suggests that BAV is also transmitted by this genus. A serological survey of two small groups of cattle raised in St. Croix and Puerto Rico, in the Caribbean, established that antibody to BAV, or a closely related virus, exists on both island. A retrospective analysis of seroconversions to BAV in sentinel calves in Florida, relative to populations of potential Culicoides vectors, failed to demonstrate any statistically significant correlation. PMID- 1871953 TI - Susceptibility of various animals and cultured cells to exfoliative toxin produced by Staphylococcus hyicus subsp. hyicus. AB - In piglets inoculated with partially purified exfoliative toxin (pp-shET) produced by Staphylococcus hyicus subsp. hyicus, exfoliation was observed at 12 h after injection. Chickens inoculated with the same dose of pp-shET also showed exfoliation within 30 min of injection. However, exfoliation was not demonstrated in mouse, rat, guinea pig, hamster, dog or cat inoculated with pp-shET until 24 h after injection. In cultured cell lines, especially L-929 and Hep-2, the rounding effect occurred after incubation with pp-shET for 1 h. The rounding effect was also seen in five other cultured cells (NCTC 2544, HeLa/S3, HmLu-1, CHO and BHK 21) 6-24 h after exposure to pp-shET. These round cells survived for 72 h after inoculation and formed a monolayer 24 h after changeover to a toxin-free medium. The rounding effect was observed in cells after the formation of the monolayer, but not before. It was suggested that the rounding effect was not caused by the increase in cyclic AMP in cells inoculated with pp-shET but by the cleavage of intracellular contacts. PMID- 1871954 TI - Competitive enzyme-linked immunosorbent assay for heartwater using monoclonal antibodies to a Cowdria ruminantium-specific 32-kilodalton protein. AB - Hybridomas producing monoclonal antibodies (mAb) to Cowdria ruminantium were raised. Four mAbs of the IgG isotype reacted in western blots with a 32 kilodalton Cowdria protein (Cr32), which had previously been shown to be conserved and immunodominant. A fifth mAb of the IgM isotype recognized a 40-kDa Cowdria protein. The latter mAb was negative in an indirect fluorescent antibody test (IFA), whereas the other four were positive. mAb No. 4F10B4 showed the strongest signal in western blots using three different stocks of Cowdria. Immuno gold labeling of Cowdria organisms in vitro using 4F10B4 showed that Cr32 has surface-exposed antigenic determinants. Using mAb 4F10B4, a competitive ELISA was developed which detected specific Cowdria antibodies in goat, sheep and cattle sera. Antibodies in animal sera competed with binding of mAb 4F10B4 to a crude sonicated Cowdria antigen obtained from infected endothelial cell cultures. The competition ELISA (CELISA) detected antibodies in 55 out of 70 (79%) goats experimentally infected with one of eight different Cowdria stocks. Fourteen out of the 15 sera which were shown negative in the CELISA were also negative in the IFA. Nevertheless, all 15 sera recognized some epitopes of the immunodominant Cowdria-specific 32 kDa protein as judged from their reaction with this protein in western blots. Overall, there was 89% agreement between CELISA and IFA considering all 70 goat sera. Moreover, antibodies were detected in nine out of nine sheep infected with one of three different stocks of Cowdria and in sera from calves experimentally infected by two different strains of heartwater. There were no cross-reactions with Ehrlichia phagocytophila antibodies in goat sera, nor with Anaplasma marginale antibodies in bovine sera. Lack of cross-reactivity and detection of antibodies to eight geographically widely distributed stocks of Cowdria, makes the competition ELISA a promising test for use in heartwater endemic areas. PMID- 1871955 TI - Alcian blue and epithelial membrane antigen are useful markers in differentiating benign from malignant papillae in thyroid lesions. AB - Immunohistochemistry for epithelial membrane antigen (EMA) and histochemistry for alcianophilic substances were performed in 17 cases of papillary thyroid carcinoma (PTC) and 11 cases of benign thyroid lesions showing papillary changes (7 diffuse hyperplastic goitres-Graves' disease; 4 colloid cystic goitres). In all PTCs the glycocalix of the cells lining the papillary structures was strongly positive with anti-EMA antiserum. Alcian blue pH 2.5 stain (AB 2.5) was also positive in 15 of these cases. In contrast, no cases of benign thyroid lesions showed AB 2.5 positivity in the cells lining the papillary structures and the positivity with anti-EMA antiserum, present in only 5 out the 11 cases, was focal and very weak. These results indicate that the presence and distribution of EMA and alcianophilic substances may be useful in distinguishing benign from malignant thyroid lesions containing papillae. PMID- 1871956 TI - Ultrastructural lipid and glycoconjugate cytochemistry of membranous lipodystrophy (Nasu-Hakola disease). AB - In order to assess the lipid and glycoconjugate characteristics of membranous lipodystrophy, a 29-year-old male with this disease was studied using an ultrastructural cytochemical approach. The specific membranocystic lesions of the disease are composed of cystic spaces and the lining membranes. The membranes were observed to have a two-layered character: microtubular structures in the layer adjacent to the spaces and a central amorphous zone. Lipid staining and the lipase digestion test revealed triglycerides localized not only in the cystic spaces but also in the microtubular structures. Lectin histochemical examination of carbohydrate components demonstrated that Maclura pomifera agglutinin bound strongly to the membranes, while Griffonia simplicifolia I, G. simplicifolia II, Concanavalia ensiformis and Triticum vulgaris agglutinin reacted weakly. Our results indicate the presence of triglycerides and carbohydrates with mainly alpha-D-galactose residues in the distinctive membranocystic lesions, in particular in the microtubular structures. PMID- 1871957 TI - The accuracy of death certificates. Implications for health statistics. AB - The death certificate is an important source of data on disease incidence, prevalence and mortality. It should therefore be as accurate and complete as possible. Death certificates from 433 autopsied hospital patients were reviewed and matched against the results of post-mortem examinations. Significant discrepancies between the two documents were observed in 50% of patients. In 25%, the immediate cause of death was incorrectly stated on the certificate, having been assigned to a different organ system in the majority of those cases. In 33%, there was disagreement on major disease other than the immediate cause of death. In 9%, the death certificate was signed before the autopsy was performed. The extent of disagreement was largely independent of whether the certificate was signed before or after the autopsy. We conclude that: (1) there is a significant discrepancy between autopsy diagnoses and entries on death certificates; (2) disagreement is not due to unavailability of autopsy data at the time of completion of the certificate; (3) death certificates should be completed or amended utilizing data gained at autopsy. PMID- 1871958 TI - A new monoclonal antibody to human subcapsular thymic epithelial cells. AB - A monoclonal antibody, termed K-20, was generated against an anaplastic thymic carcinoma cell line, Ty-82. Subcapsular thymic epithelial cells of the thymus and blood vessels in various organs were shown to react with the K-20 monoclonal antibody by immunohistochemical staining. Immunofluorescent study revealed that various haematopoietic fresh cells and cell lines did not show any significant reactivity with K-20, except for one Epstein-Barr-virus-carrying lymphoma cell line (SP-50B). Western immunoblotting and affinity purification procedure revealed that K-20 was directed to a protein with a molecular weight of 28 kDa. K 20 is unique in its restrictive reactivity with human subcapsular thymic epithelial cells. PMID- 1871959 TI - Alteration of the lung parenchyma associated with autoimmune hepatitis. AB - The clinical history, radiological and histomorphological alterations of the lung parenchyma associated with chronic active autoimmune hepatitis are described. A 6 month-old female infant developed chronic active autoimmune hepatitis associated with autoimmune haemolytic anaemia. She was treated with immunosuppressive drugs, including steroids, for more than 6 years and developed symptoms and radiological signs of interstitial pneumonitis 4 years after onset of the autoimmune hepatitis. Associated bronchiectasis was detected 1 year later. No abnormalities of lung defence mechanisms could be demonstrated. Resection of the sixth left segment and of the basal parts of the left lower lobe revealed honeycombing with changes in the lung parenchyma which included chronic interstitial pneumonitis with multinucleate giant cells, seen predominantly in the distal airways, marked diffuse interstitial mononuclear infiltrates and mild diffuse interstitial fibrosis as well as bronchiectasis and organizing pneumonia. Granulomatous lesions, angiitis and necrotic areas were absent. Immunohistochemistry for immunoglobulins was negative for IgA, IgG and IgM and positive for IgD in the multinucleate giant cells. A strong positive reaction to HLA-DR-specific monoclonal antibody was noted, whereas no specific sugar receptors (endogenous lectins) could be detected by use of biotinylated glyconeoproteins. PMID- 1871960 TI - Adenocarcinoma of the cervical oesophagus arising from ectopic gastric mucosa. The histochemical determination of its origin. AB - A case of adenocarcinoma of the cervical oesophagus was examined by employing a battery of histochemical techniques and was demonstrated to arise from ectopic gastric mucosa. The patient was a 66-year-old Japanese male. Endoscopy revealed an ulcerated tumour on the right anterior wall of the cervical oesophagus, approximately 16 cm from the incisor teeth. Pathological examination of surgically removed specimens showed well-differentiated tubular adenocarcinoma. Ectopic gastric mucosa was found in the oesophageal mucosa adjoining the carcinoma. Histochemical stains for characterizing mucosubstances and immunostains for various antigens were used. In addition to this carcinoma, ectopic gastric mucosa in the oesophagus and normal oesophageal, cardiac, tracheal and bronchial mucosa were also examined. The results showed that the carcinoma contained mucins, which showed reactivities characteristic of the gastric surface mucous cell (galactose oxidase-cold thionin Schiff reactive) and gland mucous cell (paradoxical concanavalin A staining reactive). Ectopic gastric mucosa consistently contained these mucins, but other tissue sites lacked them. PMID- 1871961 TI - Histology and virus expression in the liver: a prognostic puzzle in chronic hepatitis B. AB - Forty chronic untreated paediatric carriers of hepatitis B virus (HBV) infection, with no other causes of liver disease, were biopsied on presentation, when the disease was in the active viral replication phase. After a period ranging from 1 to 13 years, all patients underwent a control biopsy. At the time of the last biopsy, 31 of the patients were anti-HBe positive, whereas 9 persisted in the active replication phase. In this latter phase, necrotic and inflammatory lesions and the presence of nuclear HBcAg were found significantly more frequently than when replication had terminated. The necrotic and inflammatory lesions detected in the first biopsy of patients who subsequently underwent anti-HBe seroconversion were significantly more severe than in patients failing to reach seroconversion. All patients who maintained viral replication showed generalized nuclear reactivity for HBcAg on presentation; such reactivity was also found in 16 of 31 (52%) patients who reached anti-HBeAg seroconversion. All these cases had piecemeal necrosis (PMN) in the biopsy. PMN may therefore be considered as a positive prognostic factor in that it identifies those patients who may seroconvert with significant remission of liver disease. PMID- 1871962 TI - A baculovirus homolog of a Cu/Zn superoxide dismutase gene. AB - A gene with greater than 50% amino acid sequence identity to eukaryotic Cu/Zn superoxide dismutase genes (sod) was found at 19 map units in the genome of the baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV). This gene was transcribed into 1.4- and 1.5-kb RNAs late in virus infection. The two late RNAs have coterminal 3' ends but initiate from two different start points, both of which map to the central adenine of the sequence motif ATTAAG. The late gene product was found to be a low abundance 20-kDa polypeptide which was observed only upon partial purification by chloroform/ethanol extraction. Viruses with mutations in sod were able to replicate normally both in cell culture and in insect larvae. Viruses lacking an intact sod showed no evidence of a replication disadvantage even in the presence of paraquat, an inducer of superoxide anions. A viral-encoded superoxide dismutase (SOD) activity was not detected although endogenous insect SODs appeared to be induced in insect hemolymph and in other tissues following virus infection. The function of sod in the baculovirus infection process remains unclear. PMID- 1871963 TI - Reovirus 1 and 3 bind and internalise at the apical surface of intestinal epithelial cells. AB - Displacement of [125I]reovirus from the surface of L cells by homologous and heterologous reovirus serotypes has indicated the presence of two different receptors. Corresponding experiments with Caco-2 cells and apical membrane vesicles suggest either two different receptors or different affinity of each reovirus serotype for the same receptor. Binding and internalisation of reovirus at the apical surface of Caco-2 cells and apical membrane vesicles has been demonstrated and the implications of this for models of reovirus infectivity in the intestine are discussed. PMID- 1871964 TI - Preliminary X-ray crystallographic investigation of human parvovirus B19. AB - Crystals that diffract X rays to at least 8 A resolution have been grown from human B19 parvovirus empty capsids. These particles consist of VP-2 derived from a baculovirus expression system. This is possibly the first time that a self assembled empty viral capsid, grown in other than normal host cells, has been crystallized. Partial X-ray diffraction data have been collected using synchrotron radiation. The space group is P2(1)3 with a = 362 A. The particle position in the crystal cell is given, at least roughly, from packing considerations. PMID- 1871965 TI - Parvoviral target cell specificity: acquisition of fibrotropism by a mutant of the lymphotropic strain of minute virus of mice involves multiple amino acid substitutions within the capsid. AB - Unlike the prototype strain of minute virus of mice, MVM(p), the lymphotropic strain, MVM(i), cannot form plaques on monolayers of mouse A9 fibroblasts. At very low frequency, mutants arise in MVM(i) stocks which are able to plaque on A9 cells, and we report here the isolation and mapping of such a mutant, designated hr101. Analysis of intratypic recombinants containing regions of the hr101 genome substituted into the infectious clone of its parent MVM(i) shows that the ability to form plaques on fibroblast monolayers maps to the same small region of the coat protein gene which we had previously shown, by constructing intertypic recombinants, to contain the fibrotropic determinant of MVM(p) (Gardiner and Tattersall, J. Virol. 62, 2605-2613, 1988). DNA sequencing of the hr101 regions in virus stocks derived from these recombinants identified four single-base changes between the mutant coat protein gene and that of its parent. Each of these changes occurs in the same position as a similar change found between MVM(i) and MVM(p), and each of them change the amino acid encoded at that position. Three of the four changes substitute the same amino acid as found in MVM(p), and the fourth change substitutes an alanine in hr101 for a glutamic acid residue in MVM(i), in a position occupied by glycine in MVM(p). Analysis of the recombinants within this region shows that plaque formation on A9 monolayers is dependent upon the latter change plus one adjacent, MVM(p)-like change. This observation was confirmed by recreating this double mutant in the infectious clone of MVM(i) via site-directed mutagenesis. In addition to extending the host range of MVM(i) into A9 fibroblasts, the hr101 mutations have a complex effect on the virus' ability to grow lytically in a series of different T-lymphocyte cell lines. PMID- 1871966 TI - Synthetic peptides from the principal neutralizing domain of human immunodeficiency virus type 1 (HIV-1) enhance HIV-1 infection through a CD4 dependent mechanism. AB - The principal neutralizing domain (PND) of Human Immunodeficiency Virus type 1 (HIV-1) is mapped to a 24-amino acid sequence located in the hypervariable V3 region of the viral envelope protein. The PND of HIV-1 isolates from infected individuals corresponds mostly to that of the HIV-1 MN strain. We found that a peptide designed from the PND of HIV-1 MN virus greatly enhanced viral infection, while a peptide-derived PND of HTLV-IIIB virus showed at least 10-fold less efficient activity; no such effect was exhibited by the other peptides tested, including one designed from the PND of HIV-1 RF strain. The observed enhancing effect occurred in the early steps of viral infection and was not strain restricted as both MN- and IIIB-derived peptides increased heterologous virus expression, including that of the RF strain. The MN- and, to a lesser extent, IIIB-derived peptides also increased CD4 expression on the cell membrane and differentially inhibited CD4 down-regulation induced by the phorbol ester TPA and/or by the monosialoganglioside GM1; the peptides showing no viral infection enhancement had no such effects. These findings demonstrate that the viral enhancement observed took place through a CD4-dependent mechanism and suggest that the PND is involved in HIV-1 infection and spread. PMID- 1871967 TI - Evolution of the G and P genes of human respiratory syncytial virus (subgroup A) studied by the RNase A mismatch cleavage method. AB - The G and P genes of human respiratory syncytial viruses (subgroup A), isolated between 1961 and 1989, were analyzed by RNase A one-dimensional fingerprinting, using the Long strain as the reference. Total RNA extracted from cells infected with the different isolates was hybridized to radiolabeled antisense G or P RNA probes of the Long virus. The RNA:RNA heteroduplexes were digested with RNase A and the resistant products analyzed by gel electrophoresis. Comparative analysis of the cleavage patterns revealed extensive genetic heterogeneity in both genes among viruses isolated in different epidemics. In contrast, 13 viruses isolated in Montevideo during a 3-month period showed much more restricted heterogeneity; thus, 11 viruses represented the predominant type of this outbreak and only 2 other viruses generated different RNA cleavage patterns distantly related to the major type. Statistical analysis of the results obtained indicated progressive accumulation of genetic changes with time along cocirculating evolutionary lineages within the same antigenic subgroup of RS virus. The results are discussed in terms of a model for RS virus evolution. PMID- 1871968 TI - Biochemical and biophysical characterization of the reovirus cell attachment protein sigma 1: evidence that it is a homotrimer. AB - The oligomerization state of the reovirus cell attachment protein sigma 1 (49K monomeric molecular weight) was determined by biochemical and biophysical means. Full-length (protein product designated A) and C-terminal truncated (protein product designated B) serotype 3 reovirus S1 mRNA transcripts synthesized in vitro were cotranslated in a rabbit reticulocyte lysate, and the products were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under conditions which allowed for the identification of oligomeric forms of sigma 1. A total of four oligomeric protein bands (corresponding to A3, A2B1, A1B2, and B3, respectively) was consistently observed, which suggests that the protein is made up of three monomeric subunits. Biophysical characterization of purified sigma 1 using column filtration and sucrose gradient sedimentation analysis confirmed the highly asymmetric shape of sigma 1 and allowed us to determine the molecular weight of the native protein to be approximately 132K (a trimer). Similar biophysical analysis on the two tryptic fragments of the sigma 1 [N-terminal fibrous tail (26K monomeric molecular weight) and the C-terminal globular head (23K monomeric molecular weight)] yielded molecular weights of 77K and 64K, respectively, both again corresponding to trimers. We therefore conclude that protein sigma 1 is a homotrimer and provide, with supportive experimental evidence, a rationale for the anomalous behavior of the oligomeric protein in SDS polyacrylamide gels, which, coupled with chemical cross-linking studies, has in part led to the previous suggestion that sigma 1 might be a higher order oligomer. PMID- 1871969 TI - Mutagenesis of conserved region I in the DNA polymerase from human adenovirus serotype 2. AB - The functional importance of the conserved region I (YGDTDSLF) found in several prokaryotic, eukaryotic, and viral DNA polymerases has been probed by site directed mutagenesis of the adenovirus DNA polymerase (Ad Pol). Three different adenovirus-specific assays have been used to measure the in vitro activity of region I mutants of Ad Pol expressed in transiently transfected CMT-4 cells. In general, both conservative and nonconservative changes generally showed a greater than 5- to 10-fold reduction in activity in three different assays for activity. However, several replacements at the glycine residue showed activities closer to wild-type levels. For example, replacements of this glycine with cysteine (found in bacteriophage phi 29, another protein primed replication system), with serine, or with methionine had little effect on the activity observed in adenovirus specific assays, such as initiation and elongation. These studies confirm the importance of this region of Ad Pol in specific initiation and elongation reactions on Ad DNA templates. PMID- 1871970 TI - Characterization of the core promoter and enhancer of duck hepatitis B virus. AB - The core gene promoter of duck hepatitis B virus (DHBV) has been localized and an enhancer element has been found in a region of the DHBV genome immediately upstream of the core promoter. This enhancer was able to activate expression from both the core promoter and the S promoter of DHBV, as well as from the heterologous thymidine kinase and simian virus 40 early promoters, but not from the DHBV PreS promoter, which was active both in the absence and in the presence of the enhancer. The activity of the enhancer showed a preference for cell cultures of hepatic origin, suggesting a possible tissue preference in vivo. PMID- 1871971 TI - Redundant elements in the adenovirus type 5 inverted terminal repeat promote bidirectional transcription in vitro and are important for virus growth in vivo. AB - The adenovirus inverted terminal repeat (ITR) contains a number of cis-acting elements that are involved in the initiation of viral DNA replication, as well as multiple binding motifs for the cellular transcription factors SP1 and ATF. In this study, we utilized a Hela cell transcription extract to demonstrate that the adenovirus type 5 ITR promotes bidirectional transcription in vitro. Primer extension analyses demonstrated that the ITR directed transcription at initiation sites both within the terminal repeat and at fixed distances outside of the ITR. The ITR also strongly stimulated transcription at the early region 1A (E1A) initiation site when it was situated immediately upstream of the E1A TATA box region. Deletion and point mutational analyses demonstrated that two distinct cis acting elements were involved in these ITR-dependent transcriptional activities in vitro. Cellular transcription factors SP1 and ATF were previously shown to bind to these two regions. Analysis of viral mutants in vivo demonstrated that the NFIII/OCT-1 binding site and a conserved ATF motif were important for efficient viral growth. Regulatory elements in the ITR flanking region were found to functionally substitute for these sites. PMID- 1871972 TI - Construction of tobacco mosaic virus subgenomic replicons that are replicated and spread systemically in tobacco plants. AB - Two tobacco mosaic virus (TMV)-derived replicons, created by deletion of most of the 126/183-kDa open reading frame (ORF), replicated and systemically invaded tobacco plants when supported by wild type TMV. One RNA replicon contained an internal direct repeat of 476 nucleotides from the 3' end of the 30-kDa ORF. Although this RNA was replicated, most of the progeny were heterogeneous in size and smaller than the original transcript. A second TMV-derived RNA replicon, without any internally repeated sequences and containing a deletion of the 5' portion of the 30-kDa ORF as well as most of the 126/183-kDa ORF, was created and coinoculated with wild type TMV as helper. This RNA also was replicated efficiently and systemically invaded tobacco plants. An examination of the sequences of cDNA clones obtained after PCR amplification of the progeny population of this RNA replicon demonstrated that the observed size heterogeneity was due to deletions and insertions adjacent to the artificially created deletion junction. These data demonstrate that a TMV infection is capable of supporting an artificially created RNA replicon, similar to defective interfering RNAs or satellites. However, these dependent RNAs were replicated without noticeably interfering with wild type TMV symptoms or replication. PMID- 1871973 TI - A naturally occurring deletion mutant of figwort mosaic virus (caulimovirus) is generated by RNA splicing. AB - A naturally occurring deletion mutant is observed in plants infected with figwort mosaic virus (FMV), a caulimovirus. The encapsidated mutant genome is formed spontaneously in association with two different strains of FMV in four host plant species. The mutant also appears when cloned wild-type viral DNA is used as the inoculum. The deletion mutant alone is not infectious and it appears unable to replicate after its formation, even in the presence of wild-type virus. The gene for chloramphenicol acetyltransferase was inserted at different positions in the deletion mutant genome, and subsequent transient assays showed that gene expression of the mutant occurs despite the deletion. Sequence analyses of the mutant genome revealed a deletion of 1237-bp segment encompassing a major portion of the coat protein gene and the 5' end of the downstream reverse transcriptase gene. This deletion is associated with consensus signals for RNA splicing including the conserved 5' and 3' splice sites plus surrounding sequences, putative branch point(s) for lariat formation, and an extremely high adenosine content (41%) of the removed fragment. This suggests that splicing of the FMV full-length transcript has occurred prior to reverse transcription and this accounts for the presence and accumulation of encapsidated DNAs with the same deletion. PMID- 1871974 TI - Mutations within the human immunodeficiency virus type 1 gp160 envelope glycoprotein alter its intracellular transport and processing. AB - Intracellular transport and processing of the human immunodeficiency virus type 1 (HIV-1) envelope precursor polyprotein, gp160, proceeds via the endoplasmic reticulum (ER) and Golgi complex. We examined gp160 processing during the production of HIV-1 virions in transfected HeLa cells using wild-type and env mutant proviral molecular clones. Results from pulse-chase analyses indicated that a single amino acid substitution within a highly conserved domain of the env gene impaired gp160 export from the ER, leading to an increase in oligomeric forms of gp160 and a decrease in gp120 production. In contrast, gp160 which contained a mutated cleavage site was able to traverse the ER/Golgi complex, even in the absence of proteolytic processing, and become incorporated into budding virions. These findings indicate that export from the ER is a point in the intracellular trafficking of gp160 that is crucial to the production of the mature envelope components. PMID- 1871975 TI - Two bacteriophage T4 base plate genes (25 and 26) and the DNA repair gene uvsY belong to spatially and temporally overlapping transcription units. AB - The bacteriophage T4 DNA recombination-repair gene uvsY located at or near an origin of DNA replication and adjacent to the late base plate genes 25 and 26. Our present results reveal a complex transcription pattern in the region encompassing these genes. Most significantly, uvsY and two ORFs, downstream of it, all of which are transcribed from a middle promoter before the onset of DNA replication, are also part of a larger late transcription unit which includes the base plate genes 25 and 26. The late genes 25 and 26 are transcribed not only late, but also early from one or several early promoters further upstream. Translation, however, is inhibited by secondary structures which sequester the ribosome binding site in the early transcript. We discuss possible advantages of these transcriptional patterns for T4 DNA recombination, replication, and repair. The predicted and in vivo-expressed 23.9-kDa product of gene 26 is smaller than the reported size of gene 26 protein isolated from base plates, suggesting that nascent gp26 might be processed to a larger protein during assembly. PMID- 1871976 TI - The sequences of the ribonucleotide reductase genes from African swine fever virus show considerable homology with those of the orthopoxvirus, vaccinia virus. AB - Two African swine fever virus (ASFV) recombinant plasmids containing large inserts of DNA have been sequenced at random, and translations of the DNA sequence have been compared to libraries of vaccinia virus protein sequences. Among other genes identified by their extensive homology with vaccinia virus genes were the large and small subunits of ribonucleotide reductase. A 5.5-kb fragment from the Malawi (LIL20/1) strain of ASFV was identified as containing the genes for both these subunits. The fragment has been sequenced and the two genes have been found to be in a head-to-head orientation. The sequences are compared to other sequenced ribonucleotide reductase genes, and the evolutionary implications discussed. PMID- 1871977 TI - Functional domains of HIV-1 gag-polyprotein expressed in baculovirus-infected cells. AB - Seven recombinants of AcNPV harboring various forms of complete or truncated gag gene from HIV-1 were constructed to determine which functional domains of the gag polyprotein are implicated in its self-assembly and cellular localization. The p6 carboxy-terminal portion of the p15 NCgag domain appeared to be dispensable for assembly, budding, and release of gag particles by insect cells. However, all the morphopoietic information was not entirely confined to the p9 NC domain, as N myristylation could compensate for p15 NC deletion in gag assembly and the budding process. The two consensus karyophilic signals situated in the p17 MAgag domain were inefficient for targeting nonmyristylated forms of gag polyprotein to the nucleus when the p6 NC domain was deleted. In the presence of p6, or with a third, baculovirus-specific, karyophilic signal added at its N-terminus, gag particles relocated in the nucleus. These data suggested that p6 played a critical role in the conformation of gag polyprotein. PMID- 1871978 TI - Fatty acylation of rabies virus proteins. AB - The fatty acylation of rabies virus (CVS strain) proteins was investigated. [3H]palmitic acid was found to be incorporated into the glycoprotein G and to a lesser extent into the membrane-associated protein M2. The fatty acid linkage on G was sensitive to sodium borohydride, mercaptoethanol, and hydroxylamine, indicating that the linkage was of the thiolester type. Bromelain digestion indicated that the palmitoylation site on G was located in the intracytoplasmic domain or in the transmembrane domain in which there is only one cysteine in position 461. Therefore, palmitoylation is likely to occur at this position. In the case of M2, the linkage was also sensitive to hydroxylamine and sodium borohydride and to a lesser extent to mercaptoethanol, suggesting that the linkage also occurred on a cysteine. PMID- 1871979 TI - Deacylation of the hemagglutinin of influenza A/Aichi/2/68 has no effect on membrane fusion properties. AB - The effects of deacylating the H3 influenza hemagglutinin (HA) on its membrane fusion activity were investigated. Chemical deacylation caused no change in the ability of HA to fuse liposomes in vitro. Site-specific mutagenesis of the three cysteine residues in the cytoplasmic tail singly, or in combination, showed that all three were palmitoylated. Substitution of one, two, or all three cysteines with serine and subsequent lack of palmitoylation at mutated sites had no effect on the pH of the conformational change in HA required for fusion activity or the extent of fusion activity. PMID- 1871980 TI - Structural variation of La Crosse virions under different chemical and physical conditions. AB - La Crosse (LAC) virions exposed to different pHs (7.3, 6.2, and 5.4) and temperatures (37 degrees, 20 degrees, and 4 degrees) were preserved in thin layers of vitreous ice and observed by electron cryomicroscopy. Our results indicate that, at lower pH, virus particles interact with each other to form aggregates. In some cases, particles could be interpreted to have fused together. At neutral pH and higher temperatures morphological changes consistent with deformation in some particles were observed. We suggest that low pH conditions are sufficient for membrane fusion events to occur with LAC virions. PMID- 1871981 TI - Reassortants with equine 1 (H7N7) influenza virus hemagglutinin in an avian influenza virus genetic background are pathogenic in chickens. AB - Reassortants possessing the hemagglutinin (HA) gene from A/Equine/London/1416/73 (H7N7) [Eq/Lond] and five or more genes from A/Chicken/Pennsylvania/1370/83 (H5N2) [Ck/Penn] were lethal in chickens. This result demonstrates that horses can maintain influenza viruses whose HAs are capable of promoting virulence. Thus, reassortment of equine and avian influenza virus genes could generate viruses that might be lethal in domestic poultry. PMID- 1871982 TI - Phylogeny of capsid proteins of rod-shaped and filamentous RNA plant viruses: two families with distinct patterns of sequence and probably structure conservation. AB - Computer-assisted comparative analysis of all available amino acid sequences of the capsid proteins of positive strand RNA plant viruses with helical capsids is described. Two distinct families of homologous proteins were delineated through statistically significant sequence similarities, one including the capsid proteins of rod-shaped viruses (tobamo-, tobra-, hordei-, and furoviruses) and the other those of filamentous viruses (poty-, bymo-, potex-, carla-, and closteroviruses). It was concluded that the capsid proteins of all rod-shaped viruses, on the one hand, and filamentous viruses, on the other hand, evolved from common ancestors. Analysis of residue conservation patterns in the capsid proteins of rod-shaped viruses revealed maintenance of the hydrophobic core and of the (putative) salt bridge between conserved Arg and Asp residues. Sequence comparisons within the filamentous virus family expanded the observations on the relationship between the capsid proteins of potex-, carla-, poty-, and bymoviruses. Grouping of the beet yellows closterovirus capsid protein sequence, recently determined in this laboratory (Agranovsky et al., J. Gen. Virol., 1991, 72, 15-23), with those of potex- and carlaviruses was demonstrated. The coat protein of another closterovirus, apple chlorotic leaf spot virus, appeared to constitute a distinct phylogenetic lineage. Despite the lack of significant overall similarity, comparison of the alignments of the capsid proteins of the two families suggested formation of analogous salt bridges. PMID- 1871983 TI - Fluoride products--an update for the 1990's. PMID- 1871984 TI - Proceedings of the Second International Conference of the UWI Medical Alumni Association. Christ Church, Barbados, July 2-6, 1991. Abstracts. PMID- 1871985 TI - Infant care and wives' depressive symptoms. AB - Although some investigators show that division of child care between spouses is related to the psychological well-being of wives, little attention has been given to the relevance of specific dimensions of child care or to nonemployed as well as employed wives. In this study we differentiate basic child care tasks, i.e., those that are essential for the family's physical well-being from other, more supplemental, or auxiliary tasks. We hypothesize that husbands' failure to perform auxiliary child care will be distressing for wives, regardless of employment status because it contributes to perceptions of marital inequity. On the other hand, husbands' lack of participation in the more time-consuming, basic, tasks will be most distressing for employed wives because it results in an increased overall work load. We also hypothesize that when employed mothers are responsible for arranging child care, and when such care entails financial strains, they are more likely to experience psychological distress. To evaluate these hypotheses we use data drawn from a mail survey of a sample of mothers of infants. Using multiple regression analysis, we find that husbands' involvement in child care and housework, especially in the time-consuming tasks, is relatively low and that the most consistent predictor of husbands' involvement is wives' relative income. In terms of the impact of husbands' involvement on wives' well-being, lower levels of husbands' participation in auxiliary, but not basic, child care are associated with increases in reported symptoms, regardless of wives' employment status. When child care is relatively more costly, employed wives report increased symptoms of depression. We discuss these results in terms of the role played by expectations of husbands and wives about parental responsibility for child care. PMID- 1871986 TI - AIDS education and incarcerated women: a neglected opportunity. AB - Attitudes and perceptions about health, AIDS, and the need for AIDS education were explored among inmates in a women's prison in the southeastern U.S. Forty short-term inmates participated in a series of focus group interviews. A separate sample of sixteen women completed a 103-item questionnaire. Focus group participants expressed concern about AIDS within prison, sexual activity between inmates, and the institution's policy of housing seropositive women with the general inmate population. Close to half (44%) of the survey respondents believe that they were likely to be exposed to HIV in prison; most (81%) felt that AIDS education programs should discuss female homosexual activity, and nearly all respondents (94%) felt that inmates should be given an HIV antibody test upon entering prison. The study's findings confirm the need for tailoring AIDS education and prevention activities for incarcerated women. PMID- 1871987 TI - The measure of health in new mothers: a factor analysis of physical and mental health variables. AB - This factor analysis study was conducted to determine the components of health in new mothers. The 286 participants included three groups of married women: 63 first-time biological mothers, 104 first-time adoptive mothers, and 119 controls (women without children). Results for the entire participant group showed four health status factors--mental health, use of health services, work readiness, and activity--and these four factors yielded a cumulative variance of 62.8%. While three of the factors--mental health, use of health services, and work readiness- were represented in the factor structures of each of the three groups, there were noteworthy differences in the constituents of factors between groups. The current change in roles and responsibilities of new mothers calls for a careful look at the health of this group of women; the health factors identified in this study may provide useful tools for further research involving these important members of our society. PMID- 1871988 TI - Differences in the impact and management of heart disease between older women and men. AB - Findings are presented from an exploratory study of differences in the impact and management of heart disease between men and women aged 60 and over (N = 323). The sample consisted of ambulatory, non-institutionalized, cardiac patients who had agreed to participate in a self-management intervention study. Differences between men and women were found regarding symptom experience, physical functioning, exercise compliance, use of prescribed drugs, and physician/clinic visits. Differences in emotional well-being and psychosocial functioning were not found; however, women reported more stress and limitation in the area of household management. Implications for future research and practice are discussed. PMID- 1871989 TI - New Zealand Maori women's health: status and self-help action in the 1980s. AB - The indigenous Maori population of New Zealand has experienced improvements in health in recent decades but vis-a-vis the non-Maori segment of the population, Maori, and Maori women in particular, continue to be disadvantaged. The situation became the focus of attention during the 1980s. Among efforts to improve it, a broad-based self-help campaign initiated by Maori leaders, organizations and health professionals emerged as important. This paper documents the current status of Maori women's health and examines health-related self-help activities on the part of the Maori Women's Welfare League, the leading Maori women's organization. The League has taken a leading role in the self-help campaign, declared a Decade of Health for 1985-1995, and adopted a program of action that could help to significantly improve the status of Maori health. PMID- 1871990 TI - Gender differences in teenage smoking. AB - This study analyzes the patterns and correlates of gender differences in cigarette smoking in a national sample of white high school seniors in 1985. More females than males were smokers, because females had higher rates for the early stages of smoking adoption. Specifically, females were more likely to have tried smoking at least once and, among those who had tried smoking, females were more likely to have smoked more than once or twice. Gender differences in smoking varied, depending on the students' characteristics. For example, the female excess in the early stages of smoking adoption was small or absent among rural students or very religious students, apparently because traditional values inhibit smoking adoption more among females than among males. We estimated the contributions of gender differences in students' characteristics to gender differences in smoking adoption. For example, males were more involved in sports, and this appears to be one reason why males had lower rates of smoking adoption than females. On the other hand, males had more deviant behavior and attitudes, and this would be expected to contribute to greater smoking adoption by males. The findings of this study indicate important gender differences in the determinants of smoking adoption. PMID- 1871991 TI - Gender differences in the utilization of emergency department services. AB - Some of the suggested explanations of the well documented gender morbidity differences imply that these are not 'real' but the result of women's tendency to perceive and report more symptoms, to magnify symptom severity, and to seek help. To contribute to this debate, gender differences in utilization of a general hospital emergency department (ED), often used as a primary care service and for mild conditions, were studied. Data were collected from the general ED admissions registry for 6815 patients. In our data strikingly more men than women visited the ED during the period studied; generally, the same proportion of men and women were self-referred patients; and similar rates of both sexes were hospitalized regardless of type of referral. Thus, these findings suggest that, at least among ED patients, there is no gender differential in symptoms perception, evaluation, or presentation. Indications for these were somewhat found among young patients (aged 17-24) only. Alternatively, the findings with regard to this age group could reflect professional gender stereotyping at the primary care level. PMID- 1871992 TI - All-terrain vehicle injuries in central Wisconsin: a continuing problem. AB - All-terrain vehicles (ATVs) have become well recognized as associated with injuries. This recognition has resulted in attempts at education and regulation to reduce the number and severity of injuries and number of deaths. The Marshfield Clinic and St. Joseph's Hospital surveyed all-terrain vehicle accidents in the Emergency Department in 1985 and again in 1988 and followed these patients for at least 1 year after the injury. Between the two dates, extensive educational and legislative activity had taken place. The actual number of all-terrain vehicle accidents had increased. The characteristics of victims who were involved in all-terrain vehicle accidents did not change. The actual number of accidents associated with three-wheeled ATVs did not appreciably decrease but the number of accidents associated with four-wheeled ATVs did increase. To date, it is not clear that legislative and educational activities are effective in reducing the number of ATV accidents or in changing the pattern of the accidents. PMID- 1871993 TI - The importance of bicycle helmets. PMID- 1871994 TI - Elastofibroma dorsi: report of two cases and literature review. AB - Two cases of elastofibroma dorsi are added to the 125 non-Asian cases reported in the last 31 years. Rapid growth followed by spontaneous total regression is reported for the first time. Confirmation of these observations by others and tissue confirmation are encouraged. Physician awareness of elastofibromas may reveal a higher incidence of occurrence and help avoid unnecessarily radical surgery. A comprehensive review of the literature discloses several current misconceptions. PMID- 1871995 TI - Fine needle aspiration biopsy of thyroid nodules. AB - Between April 1982 and December 1988, we performed 611 fine needle aspiration (FNA) biopsies in 502 patients with solitary thyroid nodules. The biopsy results were classified as follows: unsatisfactory, 19%; benign, 53%; suspicious, 23%; and malignant, 5%. Malignant lesions were found at surgery in 24 of 25 patients with malignant cytology and 31 of 68 patients with suspicious cytology. Autonomous nodules, obviating the need for surgery, were detected in 5 of 36 (14%) patients with cytology suspicious for follicular neoplasm. We conclude that FNA biopsy of the thyroid nodule is a safe and accurate diagnostic test. Thyroid scintigraphy remains useful in patients with cytologic results suspicious for follicular neoplasm. A cost-effective strategy for managing thyroid nodules is presented. PMID- 1871996 TI - Gallup poll measures Wisconsin's opinions on health care. PMID- 1871997 TI - Malignant melanoma: trends in Wisconsin, 1980-1989. PMID- 1871998 TI - Inhibitory effect of cigarette smoking on gastric emptying of a solid meal in patients with type I gastric ulcer. AB - The effect of cigarette smoking on gastric emptying (GE) of a radio-labelled solid meal was examined in 14 patients with type I gastric ulcer diagnosed at endoscopy. The patients underwent GE measurement thrice: under basal conditions and for two smoking sessions--without and after cimetidine pretreatment (2 x 400 mg orally for 2 days and 400 mg orally 1.5 h before the isotopic GE examination). Cigarette smoking significantly delayed GE--the median GE index, Ix: 0.688 min 1.10-2 (range 0.033-1.886) after smoking vs. 1.246 min-1.-2 (range 0.384-2.339) under basal conditions, p less than 0.01. The inhibitory effect of smoking on solid GE was blunted when smoking coincided with cimetidine pretreatment--the median Ix amounted to 1.069 min-1.10-2 (range 0.022-1.462) and was not significantly different from that under basal conditions. PMID- 1871999 TI - [Endosonography versus computerized tomography in preoperative staging of esophageal cancers]. AB - The results of endosonography and computed tomography--using an optimized technique of CT--in preoperative staging of esophageal cancer are compared. In 22 of 40 patients with esophageal tumors a complete passage by the ultrasonic endoscope was possible. Endosonography was superior to CT in the assessment of early stages of esophageal tumors (T1/T2). Out of nine tumors confined to the esophageal wall, eight were classified correctly by endosonography, only five by computed tomography. The results in T3- and T4-carcinomas (13 patients) were comparable for endosonography and computed tomography. Endosonography is of importance in the selection of patients with early stages of cancer, in whom a curative resectability is still possible. PMID- 1872000 TI - [Ultrasonic diagnosis of tumors of the cecum and ascending colon]. AB - The results of preoperative ultrasound investigations were compared with the intraoperative findings in 42 patients (27 women, 15 men) operated on because of tumours of the cecum or colon ascendens. In 34 of 42 patients (i.e. 81%) the tumour could be correctly diagnosed by ultrasound. In 3 cases the investigator was not sure about imaging the tumour. Only in 5 cases (i.e. 12%) the tumour was not identified by ultrasound scanning. 4 out of these 5 patients had attended the hospital to be operated on because of a carcinoma of the rectum and the second carcinoma of the large bowel was found by chance intraoperatively. In 16 patients in whom the diagnosis of a large bowel carcinoma had not been established before, the tumour could be primarily diagnosed by ultrasound. PMID- 1872001 TI - [Endoscopic control of balloon dilatation of the pylorus]. AB - After resection of a cardia carcinoma a gastric obstruction was observed. Because of a severe esophagitis the planned operation could not be performed. In the following a method of palliative treatment of pyloric dysfunction is described. Under fluoroscopic control a stiff balloon catheter was introduced into the stomach. Under endoscopic control a guide wire fitting the central lumen of the balloon catheter was passed into the pylorus by use of a biopsy forceps. Under endoscopic and fluoroscopic control the guide wire was positioned in the duodenum. Than the balloon catheter was passed through the pylorus both, under endoscopic and fluoroscopic control and inflated. No complication was observed. After dilatation of pylorus the patient was able to take food as usual. In the following weeks the esophagitis was treated and the pyloroplasty was performed successfully. PMID- 1872002 TI - [Heraclitus or the physician]. PMID- 1872003 TI - ["Trypsinogen activation peptide"--new urine marker for early assessment of the severity of acute pancreatitis?]. PMID- 1872004 TI - [Recurrent gallstone formation after successful lysis]. PMID- 1872005 TI - [Acute vascular occlusion caused by percutaneous transluminal coronary angioplasty: early and late results of repeat-PTCA]. AB - Acute vascular occlusion after percutaneous transluminal coronary angioplasty (PTCA) often necessitates a prompt aortocoronary bypass-operation (CABG). Alternatively, a re-PTCA can be attempted. In 1500 consecutive patients there was acute symptomatic occlusion due to PTCA 5 min to 16 h after the operation in 47 cases (3.1%). An immediate re-PTCA was attempted in all cases. RESULTS: Reopening was successful in 43 of 47 cases (91%): in 15 patients (30%) within 30 min, in 36 patients (68%) within 60 min and in 42 patients (89%) within 90 min. In eight patients there was early re-occlusion 30 min to 20 h after re-PTCA, necessitating acute CABG in four patients. In 35 patients with re-PTCA the vessel remained open. Re-stenosis occurred within 1 to 10 days in 10 patients, and in additional 12 patients after 2-4 months. In most cases an additional PTCA was successful. COMPLICATIONS: Six patients had an emergency CABG (three with an exchange wire as a stent in the dissected coronary artery). Three patients died (one after CABG); 14 patients experienced myocardial infarction (30%) (in three of these 14 the infarct was large). CONCLUSION: Acute vascular occlusion after PTCA can successfully be treated by re-PTCA in four of five cases. However a rate of re stenosis of about 60% is to be anticipated. Reperfusion with re-PTCA is fast and in these patients with transmural ischemia there are obviously less complications in comparison to emergency CABG after PTCA. 60% of the patients remain symptom free or markedly improved and without infarction or emergency CABG after 4 months. PMID- 1872006 TI - [Long-term results of elective percutaneous transluminal coronary angioplasty. A clinico-angiography study of 289 consecutive patients]. AB - 289 consecutive patients (255 male, 34 female, 50 +/- 6 years) had an elective single-vessel-PTCA between October 1978 and March 1983. A clinical long-term follow-up was obtained after 4.7 (3-10) years. The PTCA success-rate was 73% with a non steerable balloon catheter being used in 95% of the cases. For 271/289 patients with follow-up (94%), the 56-month-survival rate was 96%, the incidence of non-fatal myocardial infarctions 11%, and the need for a second intervention (PTCA and/or bypass surgery) was 39%. The most favorable long-term outcome was observed in patients without need of a second intervention (97% survival, 7% non fatal myocardial infarction, 83% without cardiac complaints during everyday life), and in patients with elective bypass surgery after an unsuccessful PTCA (100% survival, 5% myocardial infarction). 32/138 (23%) of patients without a second intervention during follow-up underwent an angiographic control after an average of 4.7 years. In comparison with the first follow-up angiogram 6 months after PTCA, the mean residual stenosis at the PTCA-site showed a slight decrease. It is concluded that PTCA offers good clinical and angio-graphic long-term results in single-vessel disease, with an excellent prognosis of patients without need for a second intervention. PMID- 1872007 TI - [Incidence of tricuspid valve prolapse]. AB - The incidence of tricuspid valve prolapse and its association with mitral valve prolapse was studied in 100 patients with right- and left-ventricular angiography. Coronary artery disease was present in 81 patients (pts), a dilative cardiomyopathy in 6 pts, and a hypertrophic cardiomyopathy in 2 pts. 11 pts were angiographically normal. A total of 27 pts had a tricuspid valve prolapse, and 15 pts had a mitral valve prolapse. In 19 pts prolapse of the tricuspid valve was isolated, and in 8 pts it was associated with a mitral valve prolapse. The associated finding of a prolapse of the tricuspid and mitral valve was statistically significant (p less than 0.02). Patients with a tricuspid valve prolapse experienced a higher right-ventricular ejection fraction (58 + 10 vs 53 +/- 10%; p less than 0.05) and smaller end-systolic right ventricular volume indices (39 +/- 16 vs 47 +/- 17 ml/m2; p less than 0.05) compared to those without tricuspid valve prolapse. There was no further difference in clinical and hemodynamic parameters between those with and those without tricuspid valve prolapse. The clinical significance of a tricuspid valve prolapse is still undefined. PMID- 1872008 TI - [Course of dilatative hypertrophic cardiomyopathy]. AB - Five patients with hypertrophic cardiomyopathy developed left-ventricular dilatation and congestive heart failure during an observation period of 16-29 years. In one patient cardiac transplantation had to be performed. The initial predominant symptoms of outflow-tract obstruction and diastolic dysfunction developed into progressive left-ventricular systolic failure. The question of whether this is a well-defined subgroup of patients with hypertrophic cardiomyopathy, or whether hypertrophic cardiomyopathy turns into a phase of left ventricular dilatation and failure after some years remains to be elucidated by long-term studies. PMID- 1872009 TI - [Non-invasive detection of left ventricular diastolic function in variously trained endurance athletes during a marathon run with pulsed Doppler sonography]. AB - To evaluate left ventricular (LV) diastolic function in long distance runners LV filling parameters were assessed by Doppler echocardiography during marathon race in 23 male subjects. On the basis of their personal record the athletes were divided into two groups: 12 endurance athletes (END; 218 min over 42 km) aged 34 years (29/37, median and 25%/75%-percentiles) and 11 ultra endurance athletes (ULTRA; 152 min over 42 km) aged 32 years (28/37). At rest 21 healthy untrained subjects (UT) aged 33 years (28/37) served as control group. In long distance runners the values for LV mass and LV mass index were significantly higher in END with 210 (168/253) g rsp. 110 (87/135) g/m2 and in ULTRA with 225 (179/267) g rsp. 118 (93/142) g/m2 as compared to UT with 129 (105/162) g rsp. 68 (57/79) g/m2 (p less than 0.001 each). Doppler-derived mitral flow was characterized by the early passive (E wave) and late (A wave) diastolic inflow. In particular atrial filling fraction (AFF) as the relative atrial contribution to LV filling was measured. At rest and at km 21 we saw a normal filling behaviour (AFF = 27% bzw. 28%) in both groups of long distance runners with an AFF of 27 (26/29)% in END and an AFF of 28 (26/29) in ULTRA. In END AFF rose to 42 (38/47)% at km 42 (p less than 0.001) and remained significantly elevated with 37 (35/42)% until 30 min post marathon (p less than 0.05). Only 60 min post exercise AFF returned to baseline values with an AFF of 28 (25/39)% in END. In contrast at km 42 in ULTRA AFF was significantly lower and at baseline levels with 26 (25/29)% compared to END (p less than 0.001) and did not significantly change in the further course of the post running period. CONCLUSION: Long distance runners show a normal LV filling behaviour at rest despite significant LV hypertrophy. In contrast to top class athletes (ULTRA) there is a shift of LV filling from early (E wave) to late (A wave) diastole in less trained runners (END) during marathon. Thus, the results indicate an impairment of early diastolic LV filling in amateur endurance athletes (END) during extreme physical exercise. PMID- 1872010 TI - [Myocarditis caused by Toxoplasma gondii and Aspergillus fumigatus after orthotopic heart transplantation]. AB - This report describes the case of a 56-year-old patient, who died 53 days after orthotopic heart transplantation due to myocarditis caused by infection with Aspergillus fumigatus and Toxoplasma gondii. Aspergillosis was diagnosed by transthoracic needle aspiration of a pulmonary infiltration. Endomyocardial biopsy showed toxoplasma pseudocysts. Autopsy revealed myocardial infection with both infectious agents. Despite specific therapy, myocarditis determined the fatal outcome in this case. The value of invasive techniques for specific diagnosis of infectious diseases in immunocompromised patients is discussed. PMID- 1872011 TI - Leprosy vaccines. AB - Leprosy is the clinical manifestation of chronic infection with Mycobacterium leprae, an intracellular parasite with a predilection for skin and nerves. Disabilities and mutilations associated with this disease, which are attributable primarily to nerve involvement, have made leprosy among the most feared and stigmatizing of all diseases. It is still widespread in the warmer regions of the globe, including southern Europe, southern USA and most of the developing countries. Though widespread, the distribution of the disease in endemic regions is sparse (a prevalence rate of 1 per 1000 is high) and predominantly rural, for reasons which are not understood, but which add to the difficulty of providing effective disease control. PMID- 1872012 TI - Adverse events following measles-mumps-rubella and measles vaccinations in college students. AB - We studied adverse events reported by 401 measles, mumps and rubella (MMR) vaccinees and 391 unvaccinated controls at one college, and 133 measles (M) vaccinees and 352 unvaccinated controls at an adjacent college during a measles outbreak in Massachusetts in 1985. Rates of symptoms and signs experienced by MMR vaccinees, M vaccinees, and controls were essentially similar. No serious adverse events were detected. PMID- 1872013 TI - Effect of a synthetic adjuvant for inducing anti-tumour immunity. AB - An acylated derivative of muramyl dipeptide (MDP), 6-O-(2-tetradecyl hexadecanoyl)-muramyl-dipeptide (B30-MDP) is a strong adjuvant effective in inducing cell-mediated immunity. We used B30-MDP as an adjuvant for induction of anti-tumour immunity. Guinea-pigs which were injected repeatedly with a mixture of X-ray-treated leukaemic cells and B30-MDP dissolved in phosphate buffered saline resisted a challenge of leukaemia cells and showed no sign of leukocytosis. The immunity induced was tumour-specific and retained for more than 100 days. These results suggest that B30-MDP is useful as a simple but potent immunotherapeutic tool. PMID- 1872014 TI - Improvement of hepatitis B vaccine by the use of a new adjuvant. AB - Humoral and cellular immune responses of mice and guinea-pigs to hepatitis B virus surface antigen when alum-precipitated or administered with Syntex Adjuvant Formulation (SAF) were compared. Two doses of HBsAg in SAF were sufficient to elicit antibody responses, and using SAF the dose of antigen could be reduced to one-tenth of that required to elicit antibody responses by alum-adjuvanted HBsAg. The use of SAF increased and made more consistent the antibody responses in young mice and in strains of mice with inherited low responses to HBsAg. Cellular responses to HBsAg were more consistently observed when SAF was used than when alum was used. SAF increased the formation of IgG2a antibodies in mice except in the B10.M strain; antibodies of this isotype activate complement and act synergistically with antibody-dependent effector cells more efficiently than antibodies of other isotypes. If SAF proves acceptable for human use it could improve vaccines against hepatitis B virus. PMID- 1872015 TI - Principles of selective inactivation of viral genome. V. Rational selection of conditions for inactivation of the viral suspension infectivity to a given extent by the action of beta-propiolactone. AB - The influence of the initial concentration of beta-propiolactone, the composition of the solution, temperature, and pH on the bacteriophage MS2 infectivity inactivation kinetics has been studied. Rate constants have been determined for the infectivity inactivation and for the change in the concentration (the consumption) of the reactant under inactivation conditions. These constants have been shown to permit a sufficiently precise description of the phage MS2 survival curves under the action of beta-propiolactone. These data have been used to put forward a kinetic approach for the rational determination of conditions for inactivation of the viral infectivity to a required extent with agents whose concentration decreases during inactivation as a result of hydrolysis and reactions involving the medium components. PMID- 1872016 TI - Changes of the immunological patterns against measles, mumps and rubella. A vaccination programme studied 3 to 7 years after the introduction of a two-dose schedule. AB - A two-dose vaccination programme using a combined measles, mumps and rubella vaccine (MMR) and administration at the ages of 18 months and 12 years was introduced in 1982. The 12-year-old schoolchildren were tested yearly from 1985 to 1989 on serum samples obtained prior to and after vaccination. Each year between 420 and 756 children were tested. The method used for antibody testing was the haemolysis-in-gel (HIG) assay. For measles also the enzyme-linked immunosorbent assay (ELISA) and the neutralization titre (NT) were applied. Only minor variations of the prevaccination immunity to measles were seen during the period 3-7 years after introduction of the programme. The age groups studied had partly been vaccinated against measles earlier. Between 12 and 16% lacked prevaccination immunity. In contrast the immunity to mumps and rubella of the 12 year-old children decreased considerably during the study period. No general vaccination against these diseases had been performed. Thus the susceptibility to mumps increased from 14% in 1985 to 39% in 1989 and to rubella from 41 to 57%. The seroconversion rate of children seronegative for measles was high, i.e. 100% in 1985 and later varied between 96 and 97%. For mumps, the seroconversion rate was lower and varied between 72 and 88%. All sera converted to rubella. During the follow-up period there was a declining incidence of measles, mumps and rubella. The relationship between the vaccination and reduction of disease and natural immunity strongly suggests that the association is causal and that this vaccination policy reduced the transmission of infection. PMID- 1872017 TI - Programmed antigenic stimulation: kinetics of the immune response to challenge infections of mice primed with influenza inactivated whole virus or neuraminidase vaccine. AB - Mice were immunized with either inactivated whole virus influenza A (H3N2) virus (WV) vaccine or with purified N2 neuraminidase (NA) vaccine then challenged with mouse-adapted homologous infective virus at intervals of 1-141 days later in order to ascertain the optimal vaccine-infection interval for induction of resistance to subsequent infection. Measured by serological or infection suppressing response, this interval was 15 days for both vaccines. Maximal reduction in pulmonary virus replication during initial (postvaccination) infection was achieved with WV vaccine, but in second infection by NA vaccine. This study provides further support for the concept of infection-permissive immunization with NA vaccines and suggests the promise of programmed antigenic stimulation by coupling of non-replicating and replicating antigens in the induction of solid immunity. PMID- 1872018 TI - Enhancement of in vivo and in vitro T cell response against measles virus haemagglutinin after its incorporation into liposomes: effect of the phospholipid composition. AB - Artificial phospholipid bilayer vesicles were tested for their capacity to enhance the priming and the restimulation of mouse T cells against the haemagglutinin (H) glycoprotein of the measles virus in vivo and in vitro. H glycoprotein was purified and incorporated into liposomes made of cholesterol, dicetylphosphate and dilauroylphosphatidylcholine (DLPC) or distearoylphosphatidylcholine (DSPC). H in DLPC or DSPC-liposomes was found to be a potent in vivo stimulator of lymph node T cells harvested from mice immunized with measles virus, whereas H glycoprotein in free form did not elicit any proliferative T cell response. When used to immunize naive mice, only H in DSPC liposomes was able to prime T cells as evidenced by the capacity of lymph node cells to proliferate in the presence of H in liposomes or measles virus as secondary stimulating agents in vitro. H-specific T cell clones derived from animals immunized with H in DSPC-liposomes were able to recognize H glycoprotein both in free form and incorporated into liposomes in the presence of naive spleen cells as APC. However, compared with the liposome forms, 20-fold more H protein in free form was required to elicit a T cell clone response at a similar level. This liposome immune enhancing effect on the T cell clone recognition of H glycoprotein was also observed when peritoneal exudate cells were used as APC. These data demonstrate that the insertion of a membrane-derived antigen into artificial membranes may be a prerequisite for the priming and stimulation of specific T cells both in vivo and in vitro. In addition, the nature of the phospholipid used to build the liposomes appears to be a critical parameter. PMID- 1872019 TI - Comparative safety and immunogenicity of yeast recombinant hepatitis B vaccines containing S and pre-S2 + S antigens. AB - One hundred and four healthy, hepatitis B virus (HBV) seronegative males were enrolled in a single blind, randomized pilot study to compare antibody and clinical responses to a yeast recombinant pre-S2 + S vaccine and a yeast recombinant S antigen vaccine (Recombivax HBR). Participants received either a 12, 24 or 48 micrograms dose of pre-S2 + S vaccine (with a 1:5 ratio by weight of pre-S2 and S antigens) or a 10 micrograms dose of Recombivax HBR by intramuscular injection at 0, 1 and 6 months; their serological and biochemical responses were measured at 0, 1, 2, 3, 6 and 7 months, while their clinical responses were monitored for 5 days after each injection. The proportion of vaccines with minor local or systemic complaints (mainly sore arm, malaise, myalgia, fatigue) and the proportion developing antibody to surface antigen (anti-HBs) were similar for all vaccine groups. Transient elevations in alanine aminotransferase occurred infrequently. By 7 months almost all vaccinees developed anti-HBs, but titres were generally higher among recipients of pre-S2 + S vaccine. Antibody to pre-S2 antigen developed in 70-75% by 2 months and in 91-96% by 7 months. These data imply that the recombinant yeast pre-S2 + S vaccine is as well tolerated and as immunogenic as Recombivax HBR. Further studies are being conducted to assess antibody responses in larger numbers of healthy adults as well as in special populations with sub-optimal responses to currently licensed hepatitis B vaccines. PMID- 1872020 TI - Algammulin, a new vaccine adjuvant comprising gamma inulin particles containing alum: preparation and in vitro properties. AB - Crystallization of inulin with alum forms a fine (1-2 micron) suspension of electron-dense ovoids; the alum is embedded in inulin particles, which are then converted to the immune stimulant polymorphic form, gamma inulin. This very stable hybrid preparation is termed Algammulin. Preferred conditions for its preparation are described. The alum still adsorbs protein. Gamma inulin is equally able to activate the alternative pathway of complement in vitro whether free or combined as Algammulin. Gamma inulin, either free or combined as Algammulin, dissolved on heating over a narrow temperature range that can be used to characterize the polymorphic form of the inulin. PMID- 1872021 TI - Virulence phenotype and genetic characteristics of the T32-ISTRATI Shigella flexneri 2a vaccine strain. AB - The T32-ISTRATI strain, which has been used as an oral attenuated Shigella flexneri 2a vaccine, has lost the invasive phenotype due to a spontaneous deletion in the shigella virulence plasmid. This deletion has eliminated three plasmid loci (ipaBCDA, invA and virG) that are necessary for production of a positive Sereny test by Shigella species. Virulence in the Sereny test was reconstituted in the T32-ISTRATI strain by the conjugal transfer of an intact 140 M Da virulence plasmid from S. flexneri 5. The T32-ISTRATI vaccine is safe when given orally in multiple doses of 50-100 x 10(9) organisms, and both homologous and heterologous protection has been reported in large Romanian and Chinese field trials. Although the protective antigen(s) in this vaccine have not been identified, the potential use of non-invasive plasmid deletion mutants as living shigella vaccines is illustrated by the T32-ISTRATI vaccine. PMID- 1872022 TI - Immunogenicity achieved by the intradermal hepatitis B vaccination programme for US Army soldiers in Korea. AB - Hepatitis B virus (HBV) infections are a significant threat to the 30,000 US Army soldiers stationed in South Korea. Hepatitis B surface antigen carrier rates in some Korean populations may run as high as 15%, and HBV incidence estimates for US soldiers in Korea have ranged from 0.6 to 6% per year. In response to this threat, on 1 October 1986 the US Army instituted a mandatory three-dose (0, 30 60, and 60+ days), 0.1 ml per dose, intradermal (i.d.) immunization regimen for all soldiers bound for permanent assignments in Korea. Although shown to be immunogenic in experimental studies, the i.d. route had never been attempted on as large a scale as in this operational setting. During September 1987, an evaluation of programme compliance and immune response was conducted. For those who received three doses according to schedule, antibody response was similar to that reported by previous controlled trials that used the i.d. approach. The three-dose i.d. series appeared to provide protective antibody levels in at least 67% of soldiers, but, consistent with previous trials, antibody levels were approximately one-half those obtained following intramuscular vaccination. We conclude that, as a cost-reduction strategy, wide-scale use of intradermal hepatitis B vaccine may be useful in situations characterized by short-term increased HBV infection risk. PMID- 1872023 TI - Antibody response of pregnant women to two different absorbed tetanus toxoids. AB - The antibody response in pregnant women vaccinated with either of two different adsorbed tetanus toxoids has been studied. One vaccine (A), prepared by toxoiding purified tetanus toxin followed by its adsorption onto calcium phosphate, exhibited a low titre expressed as international immunizing units, 69 IIU/0.5 ml. The other vaccine (B), prepared by purifying formalinized crude tetanus toxin and adsorbing it onto aluminium phosphate showed a high titre, 212 IIU/0.5 ml. No significant differences between titres of circulating antibodies were obtained after the first injection of either vaccine, but titres after the second injection were much higher for vaccine A as compared with those obtained using vaccine B. The results showed that the immune response in human beings is not correlated to titres expressed in IIU. These results confirm that other methods should be adopted for evaluating the potency of vaccines. A simplified technique based on the comparison of circulating antitoxin levels after vaccination of mice has recently been proposed. PMID- 1872024 TI - Passage of molecules through yeast cell walls: a brief essay-review. PMID- 1872025 TI - Inositol biosynthesis: Candida albicans and Saccharomyces cerevisiae genes share common regulation. AB - The Candida albicans inositol biosynthetic gene and its regulation have been studied. The gene, CalNO1, was cloned on a multicopy vector by complementation of a Saccharomyces cerevisae mutant strain. Southern blot analysis established that the cloned DNA was C. albicans genomic DNA in origin; neither rearrangements nor pseudogenes were evident. Blot hybridization analysis using RNA isolated from C. albicans revealed that a single RNA species (1.8 kilobases) was homologous to the cloned DNA fragment. The steady-state levels of these transcripts were shown to be regulated in response to inositol in the growth media. In addition, the steady state levels of the RNA encoded by the cloned C. albicans DNA present in S. cerevisiae on a plasmid (YRpCalNO1) were regulated in response to exogenously provided inositol. The cloned C. albicans DNA fragment was shown to restore inositol-1-phosphate synthase activity to a S. cerevisiae mutant strain defective in this enzyme. This activity was also shown to be regulated in response to the presence of inositol in the growth media. PMID- 1872026 TI - Optimization of Bacillus alpha-amylase production by Saccharomyces cerevisiae. AB - Production of Bacillus amyloliquefaciens alpha-amylase by Saccharomyces cerevisiae using the multicopy plasmid pAAH5 and ways of improving the yields of secreted enzyme were studied. In standard non-buffered medium, alpha-amylase was rapidly inactivated but stabilization of the pH at 6 led to stable accumulation of alpha-amylase in the culture medium. Removal of 1100 bp of the upstream sequence of the ADH1 promoter present on pAAH5 resulted in delayed but increased alpha-amylase production: 29-fold in selective medium, two-fold in non-selective medium. With the original ADH1 promoter, accumulation of alpha-amylase in the medium started to level off before the cultures reached stationary phase and was very low when exponentially growing cells were transferred from glucose to ethanol. This coincided with the appearance of a mRNA larger than the alpha amylase messenger. With the shortened promoter, the normal-size alpha-amylase mRNA was detected under all growth conditions and alpha-amylase was efficiently secreted into the medium also late in stationary phase and after transfer to ethanol. Highest total yields of alpha-amylase were obtained with the short promoter in non-selective glucose-containing medium; this may be explained by the greater final cell density obtained. However, the production of alpha-amylase per cell mass was higher in ethanol-containing selective medium. Seventy to eighty per cent of the alpha-amylase activity was secreted into the medium independent of the total amount produced. PMID- 1872027 TI - DNA insertions in the 'silent' regions of the 2 microns plasmid of Saccharomyces cerevisiae influence plasmid stability. AB - The 2 microns plasmid of the yeast Saccharomyces cerevisiae is in principle a suitable vector for expression of foreign genes, due to its high copy number and extreme stability. However, the cloning of genes into 2 microns often results in a reduced copy number and/or reduced stability. One reason for this observed instability could be that the inserts in general were made in one of the several open reading frames (ORFs) of the plasmid. Therefore we studied the effect on stability of insertions in the silent regions of 2 microns without interrupting any known essential regions or ORFs. Using the SnaBI site, a yeast-integrating plasmid (Yip5) was introduced into the region between the ARS and STB locus in two possible orientations. The resulting plasmids could be stably maintained in the cells without the need for complementation by the wild-type 2 microns plasmid. However, the stability of these plasmids in a cir. host was still one to two orders of magnitude lower (0.2% and 0.8% respectively) as reported for the wild-type 2 microns (0.01%). Removal of 2 kb of the bacterial sequences from Yip5 did not increase stability. The stability was dependent on the orientation of the insert. We found that in the less stable orientation, transcription originating from the insert was running into the STB region. DNA inserted in the XmaIII site located outside the ORFs in the REP2/FLP intergenic region influenced both stability and copy number of the plasmid. These effects are strongly dependent on the size of the insert. Insertion of a 2 kb DNA fragment increased the copy number, probably through an effect on FLP expression. PMID- 1872028 TI - Induction of a heat-shock-type response in Saccharomyces cerevisiae following glucose limitation. AB - The protein pattern of yeast cells which have arrested proliferation in response to glucose exhaustion is drastically different from that of exponentially growing cells (Boucherie, 1985). In this study, we used two-dimensional gel electrophoresis to characterize the protein events responsible for these alterations. We found that the induction of heat-shock proteins is one of the major events responsible for these changes. This induction accounts for the synthesis of 18 of the 35 novel polypeptides observed in glucose-limited cells. It was shown to occur in combination with two other protein events: the derepression of carbon catabolite repressed proteins, which accounts for the synthesis of the other novel polypeptides, and an arrest of the synthesis of almost all the proteins present in exponentially growing cells. The time course of each of these events was determined by carrying out a detailed analysis of the pattern of proteins synthesized at various stages of a culture exhausting its glucose supply, and by the measurement of the rate of synthesis of individual polypeptides. The results showed in particular that the synthesis of most of the heat-shock proteins synthesized in glucose-limited cells was induced closely before glucose exhaustion, and that this synthesis was transient, climaxing by the time glucose was exhausted. Under the culture condition investigated, the entry into stationary phase associated with glucose limitation began several hours before glucose exhaustion. It was thus concluded that the observed induction of heat-shock proteins is directly related to the nutritional limitation and is independent from the arrest of cell proliferation. PMID- 1872029 TI - A new glucose-repressible gene identified from the analysis of chromatin structure in deletion mutants of yeast SUC2 locus. AB - We have previously shown that some changes occur in the chromatin structure of the 3' flank of the yeast SUC2 gene in going from a repressed to an active state. In an attempt to find out the causes of these changes, we have carried out experiments in which mutant copies of SUC2 locus lacking either 5' or 3' flanks have been analysed for their transcriptional activity and chromatin structure. These experiments allowed us to discard any relationship between SUC2 transcription and chromatin changes within its 3'flank. Sequencing of this flank and mRNA analysis, however, resulted in the location of a putative peroxisomal 3 oxoacyl-CoA thiolase gene (POT1), which is repressible by glucose. The disruption of the gene produced a yeast strain unable to use oleic acid as a carbon source. This is the first time that chromatin structure analysis has permitted the identification of a new gene. PMID- 1872030 TI - Two genes encoding putative mitochondrial alcohol dehydrogenases are present in the yeast Kluyveromyces lactis. AB - Four structural genes encoding isozymes of the alcohol dehydrogenase (ADH) system in the yeast Kluyveromyces lactis have been identified by hybridization to ADH2 DNA probes from Saccharomyces cerevisiae. In this paper we report on the isolation of KlADH4 and the complete sequencing of KlADH3 and KlADH4, two genes which show high homology to KlADH1, the ADH gene previously isolated in K. lactis, and to the ADH genes of S. cerevisiae. When compared with KlADH1, both KlADH3 and KlADH4 encode amino-terminal extensions which show the characteristics of the mitochondrial targeting sequences. These extensions are poorly conserved both at the nucleotide and the amino acid level. Surprisingly, the KlADH4 extension shows a higher identity at the amino acid level to the one encoded by ADH3 of S. cerevisiae than to the KlADH3 presequence. KlADH3 and KlADH4, in contrast to the ADH3 gene of S. cerevisiae, show a strong bias in the choice of codons. PMID- 1872031 TI - Multi-functional DNA proteins in yeast: the factors GFI and GFII are identical to the ARS-binding factor ABFI and the centromere-binding factor CPF1 respectively. AB - GFI and GFII are abundant DNA-binding proteins in the yeast Saccharomyces cerevisiae. Binding sites for GFI conform to the sequence 5'-RTCRYNNNNNACG-3'. This consensus can also accommodate the recognition sequence for the ARS1-binding factor ABFI. Results of retardation-competition assays, limited proteolysis experiments, molecular weight determinations based on denaturation-renaturation procedures and mobility shift assays of protein-DNA complexes formed in the presence of a monoclonal antibody raised against ABFI suggest strongly that GFI and ABFI are the same protein. Similarly, GFII appears to be identical to the centromere-binding protein CPF1 (alias CP1), since both proteins bind to the CDEI motif of yeast centromeres (5'-RTCACRTG-3') and cannot be detected in a cpf1 disruption mutant yeast strain. In addition, based on denaturation-renaturation studies, both factors appear to have molecular weights in the same range of 53-62 kDa. PMID- 1872032 TI - The complete sequence of the unit YCR59, situated between CRY1 and MAT, reveals two long open reading frames, which cover 91% of the 10.1 kb segment. AB - We have entirely sequenced YCR59, which is a 10.1 kb segment of the right arm of chromosome III, and is part of the clone E5F from the Newlon collection. The segment contains two long open reading frames (ORFs): YCR591 which starts in the adjacent fragment H9G (situated towards CRY1 and the centromere), and continues with 1833 codons in YCR59. The second ORFYCR592 is 1226 codons long and encoded entirely within YCR59. The two ORFs represent 91% of the total length of the segment. Excellent agreement in both location and length is found between the ORFs YCR591 and YCR592 and the transcripts 86 and 87 respectively in the Yoshikawa and Isono (1990) map of chromosome III. The two ORFs correspond to new genes and show no significant similarity with any known genes. PMID- 1872034 TI - Inhibitors of human and bovine trypsin and chymotrypsin in fenugreek (Trigonella foenum-graecum L.) seeds. Isolation and characterization. AB - Three fenugreek inhibitors (TFI-A8, TFI-N2, and TFI-B2) were isolated from an inhibitor preparation by anion exchange chromatography and subsequent preparative isoelectric focusing using immobilized pH gradients and the canal technique. The purified inhibitors inhibited the enzymes tested differently: TFI-A8 exhibited a high inhibition of trypsin (8.2 mg human trypsin/mg and 8.1 mg bovine trypsin/mg) and a very low inhibition of chymotrypsin (0.8 mg human chymotrypsin/mg and 1.0 mg bovine chymotrypsin/mg). TFI-N2 inhibited the four enzymes to about the same extent (5.0 mg/mg human and 4.1 mg/mg bovine trypsin; 4.9 mg/mg human and 3.7 mg/mg bovine chymotrypsin). TFI-B2 displayed a high inhibition of trypsin (7.5 mg/mg human and 5.1 mg/mg bovine) and a low inhibition of chymotrypsin (1.8 mg/mg human and 1.9 mg/mg bovine). On average, the human enzymes were inhibited better than the bovine ones by the purified inhibitors. The inhibitors contained high amounts of cystine (five or six disulfide bridges per molecule), aspartic acid, threonine, serine and proline, no valine and methionine and two of them also no tryptophan. Their molecular masses were about 6 kDa. Their inclusion into the Bowman-Birk soybean proteinase inhibitor family is discussed. PMID- 1872033 TI - Sequence of the CDC10 region at chromosome III of Saccharomyces cerevisiae. AB - A 4.74 kb DNA fragment from the right arm of chromosome III of Saccharomyces cerevisiae, adjacent to the centromere region was sequenced. Four open reading frames with an ATG initiation codon and larger than 200 bp were found in this fragment. The largest open reading frame of 966 bp was identified as the CDC10 gene. PMID- 1872035 TI - [Quality and topography of head and face pain in patients with dysfunction pain syndrome]. AB - 264 patients with the dysfunction-pain-syndrome (DPS) and with headache were examined in finding characteristic pain quality, pain intensity and pain locations. With the 24 adjective word list we could find 9 special adjectives for the Patients with the DPS. With the pain intensity test we found that 30% of the patients had very strong pains. Out of the pain location list the main locations were the area in front of the ears, the temples, the forehead, the area around the eyes and the upper jaw. This shows that all patients had chronic pains. PMID- 1872036 TI - [Biocompatibility of precious metal dental alloys]. AB - The local toxicity of three dental gold alloys was examined by help of intramuscular implantation tests in rabbits. For each alloy implantation periods of 1, 2, 4, 8, and 12 weeks were used. The local tissue reactions (foreign body reactions) were judged and graded by use of quantitative histomorphometry. Furthermore specific cellular parameters were examined with semiquantitative histopathologic methods to get an toxicity index for each material. The local tissue reactions caused by the implanted dental alloys were judged in relation to those, caused by biological inert materials (titanium, aluminum-oxide-ceramics) respectively materials with well-known toxic potential (polyvinyl-chloride with toxic aids), after intramuscular implantation in the same animals. Significant differences were found in the tissue reactions caused by the dental gold alloys; an gold alloy with lower noble metal content elicited stronger tissue reactions than both gold alloys with high noble metal content did. PMID- 1872037 TI - [Occlusion and dysfunction symptoms]. AB - A sample of 81 students were examined for symptoms and signs associated with mandibular dysfunction. Women had a higher prevalence of these signs, which occurred statistically significant more frequently in subjects showing occlusal disturbances. PMID- 1872038 TI - [Marginal adaptation of SR-Isosit composite inlays. In vivo results after 12 months]. AB - The present in vivo study assessed the marginal behaviour of in total 43 "SR Isosit" composite inlays. SEM-analysis of replica models indicated a continuous loss of marginal adaptation within the one year period of clinical use. Cavomarginal degradation predominantly took place on the contact surface between composite resin inlay and resin luting agent by (micro-)fractures of thin and instable inlay margins. PMID- 1872039 TI - [Investigation of baker's caries in bakery and confectionary students]. AB - If the labial surfaces of a baker's teeth are attacked by caries, this will be accepted to be a result of his occupation by German laws, although it is only based on suppositions. The results of our investigations showed, however, that bakers do not have more caries of this pattern than the rest of the population. The DMFS-score, on the other hand, is somewhat higher by bakers over 30 years of age. PMID- 1872040 TI - [Can choice of medications and adjuvants reduce risks of local anesthetic complications?]. AB - Local anesthetic agents in high concentrations may cause local irritation by ischemia especially after the use of adrenaline whereas felypressin has no tissue irritating properties. Adrenaline but not felypressin increases the intravenous systemic toxicity. Noradrenaline has to be avoided as a vasoconstrictor. An aspiration test before injection will decrease the risk of inadvertent intravenous injection. PMID- 1872041 TI - [6-methoxy-2-naphthylacetic acid level in plasma, synovial fluid and adjacent tissue in patients with rheumatoid arthritis or gonarthroses after a 4-day therapy with nabumetone (Arthaxan)]. AB - The concentration of 6-methoxy-2-naphthyl acetic acid (6-MNA) in plasma, synovial fluid, synovial tissue and fibrous capsule tissue was determined in an open study with 20 patients scheduled for knee joint surgery after oral treatment with nabumetone (Arthaxan) under steady state conditions. 6-MNA is the principal metabolite of the prodrug nabumetone arising from an extensive first-pass metabolism in the liver. The patients suffering from rheumatoid arthritis (n = 12) or osteoarthritis stage III or IV (n = 8) received a daily dose of 1 g nabumetone nocte starting 4 days prior to surgery. On day 1 an additional loading dose of 1 g nabumetone was given in the morning. At the time of surgery (day 5) simultaneously blood and synovial fluid was aspirated and after medial opening of the knee joint biopsies of synovial tissue and fibrous capsule tissue were taken. The samples were analysed employing HPLC. After 4 days of treatment mean 6-MNA concentration in plasma was 40.76 micrograms/ml, in synovial fluid 34.79 micrograms/ml, in synovial tissue 19.33 micrograms/g and in fibrous capsule tissue 11.43 micrograms/g. Under steady state conditions mean synovial fluid levels of 6-MNA were higher than after application of a single dose. PMID- 1872042 TI - [Felbinac gel for treatment of localized extra-articular rheumatic diseases--a multicenter, placebo controlled, randomized study]. AB - 281 patients with extra-articular rheumatic disorders (enthesiopathy, bursitis, tendinosis, fibrositis) and moderate or severe localized pain during rest or movement in shoulder, neck, elbow or knee were randomized into groups and treated for 14 days in a double blind study with either 1 g Felbinac Gel 3% (biphenyl acetic acid) three times daily (N = 142) or with the gel formulation only (N = 139). In 50% of the patients treated with Felbinac Gel compared to 29% of the placebo treated patients (p = 0.001), the investigator assessed the global therapeutic success to be good or very good. The magnitude of complaints judged on the basis of a visual analogous scale by patients and doctor showed a significant improvement in pain reduction during rest or activity after 14 days of treatment in the Felbinac group. The rheumatic complaints diminished equally according to patient judgement in both treatment groups and the concomitant use of paracetamol was low in both groups. No significant side-effects or changes in laboratory parameters were observed during therapy. Felbinac Gel therefore is suitable for a low-risk topical therapy of soft tissue rheumatic disorders. PMID- 1872043 TI - [Intra-articular osteoid osteoma: a rare cause of coxitis]. AB - Osteoid-osteoma is a frequent benign tumor of the bone. In cases with peri- or intraarticular localisation symptoms suggestive of arthritis may occur. We report on a 25-year-old patient with a painful hip during exercise as well as in the night. Conventional radiographs were unremarkable. However, ultrasound and computertomography revealed joint effusion of the hip. Scintigraphic and tomographic findings were compatible with an osteoid osteoma. Histology of the surgically removed tumor confirmed this diagnosis. Moreover, a lympho-follicular synovitis was found. PMID- 1872044 TI - [New pathogenetic aspects of ankylosing spondylitis]. AB - Ankylosing spondylitis is one of the oldest diseases in humans; however, it is still one of the most fascinating and mysterious in human pathology. The unusual combination of both fundamental pathological processes: inflammation and ossification (which are mostly independent in respect to time and place) is unique. Until 1973, ankylosing spondylitis did not attract much immunological research. After the detection of an association between HLA B27 and the disease, clinical and immunological research was stimulated. It was supposed that HLA B27 may be a pathogenic factor. Meanwhile, it has become well known that HLA B27 itself is not required for development of the disease; however, discovery of immunological cross-reactivity between HLA B27 and some Klebsiella antigens inspired pathogenic considerations. It is discussed that the structural similarities between enteric bacteria and HLA B27 induce autoantibodies, or that HLA B27 plays a role in antigen recognition. Possibly, HLA B27 may also act as a receptor for infectious agents and their products. Fascinating, but controversely discussed is the hypothesis that bacterial products modify the B27 molecule and, in this way, trigger the disease. All present theories about pathogenesis of ankylosing spondylitis are unsatisfactory, because many important questions cannot be answered. There are no explanations for the unusual affinity of possible pathogenic immune reactions to the spine and other organs, the induction of ossification, the merging of cartilage, or the development of sacroilitis. Especially, we do not know the important bridge (if one exists) between inflammation and ossification. The typical ossification of the spine is of dramatic consequence for the patient in respect to function and mobility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872045 TI - [Morphology and growth behavior of synovial cells in monolayer culture]. AB - Synovial fluid cells from patients with rheumatoid arthritis, psoriatic arthritis, peripheral arthritis in ankylosing spondylitis, dialysis arthropathy, osteoarthrosis, and joint disorders due to acute trauma were grown in monolayer cultures and examined by light and electron microscopy at arbitrarily chosen times and in various subcultures. The cultivated cells from these sources were compared with the cells of synovial tissue (cultured under the same conditions) from patients with osteoarthrosis and traumatized joints. Our results are not in agreement with those of most other authors. In contrast to many authors, we could not find any differences between the cultures from synovial fluid and the cultures from synovial tissue: the same cell types were observed with a slight quantitative difference in both cultures. Furthermore, no morphological features (except an abundance of filopodia of rheumatoid polykaryocytes) which would be characteristic of the rheumatoid synovial cells could be determined. Due to our experiments the synovial fluid seems to be more advantageous than synovial tissue for cell culture studies of different types of arthritis. This may be attributed to the following factors: a) the easy accessibility of synovial-fluid samples by ambulant aspiration from affected joints; b) the possibility of repeating this procedure frequently without any essential danger for the patient; c) the maintainability of synovial fluid (when chilled to 4 degrees C) up to 2-4 days without cessation of the growth ability of the cells under normal culture conditions. Apparently, synovial fluid represents an appropriate medium for synovial cells to survive in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872047 TI - [Acute muramyl dipeptide-induced arthritis in the baboon Papio cynocephalus]. AB - Daily subcutaneous injections of muramyl dipeptide (MDP) for 14 days into yellow baboons (Papio cynocephalus) caused polyarthritis with a prolific fibrinous exudate, but slight synovial lymphocytosis. In contrast, a single injection of bovine serum albumin (BSA) induced only a low-grade synovitis of the ipsilateral knee. When the schedules were combined the histological features suggested an additive effect between the reactions to BSA and to MDP. Larger amounts of MDP diminished the severity of the synovitis but provoked visceral granulomata. PMID- 1872046 TI - Complement C3 cleavage product in synovial fluids detected by immunofixation. AB - 54 synovial fluids (SFs), 46 of them derived from various inflammatory diseases (30 rheumatoid arthritis (RA) SFs, 8 undefined arthritis (UA) SFs, 8 psoriatic arthritis (PSA) SFs) and 8 SFs from degenerative joint diseases (OA) were tested for C3c split product, using the immunofixation method. There were significant differences in the C3c product between the four groups investigated. In the OA group in the mean the percentage of C3c was low in comparison to the native C3 (C3c = 2.95%). RA SFs and UA SFs showed considerably higher values (20.1% for RA and 23.2% for UA) which were statistically significant in comparison to the OA SFs. With the exception of one SF the PSA SFs exhibited a relatively low percentage of the cleavage product. Despite the one high value the average C3c content of the PSA SFs was not statistically different from the OA SFs. In contrast to this low percentage of the C3c split product the PSA SFs showed the highest C3 concentration of all groups (87.0 +/- 36.5 mg/100 ml). Immunofixation is a simple and effective tool to determine the C3c split product in SFs. It might also be helpful for establishing the differential diagnosis of PSA vs RA on the basis of the C3 level of the SF in those patients where an elevated level of C3 is present. PMID- 1872049 TI - [Sterilization--disinfection in the dental office]. PMID- 1872048 TI - The role of cartilage minor collagens in inducing arthritis. AB - Arthritogenic properties of native types IX, XI, and II collagen were investigated in female Wistar rats. Immunization with native type-XI or -II collagen led to the arthritic reaction in 60% of investigated rats. After boosting, a distinct increase in anticollagen antibodies was observed followed by temperature rise (swelling and redness of affected joints). At the end of the experiment (after 7 weeks) subchondral bone destruction was detectable upon x-ray examination. Histological observation of the affected knee and ankle joints showed progressive destruction of the articular cartilage and subchondral bone accompanied by proliferative synovitis with extensive formation of fibrous tissue found in joints of rats immunized with native type-XI collagen. Immune response to collagen types (determined by ELISA) reached its peak between the 14th and the 21st day. From the acute stage to the chronic stage a decrease of serum anticollagen antibodies was observed to remain constant. Rats immunized with native type IX and denatured type XI collagen did not develop arthritis. PMID- 1872050 TI - [Goethe and the intermaxillary bone. "I have found neither gold nor silver..."]. PMID- 1872051 TI - [Dental treatment measurements in children using audioanalgesia]. PMID- 1872052 TI - [Structure of proximal surfaces of amalgam restorations under the scanning electron microscope]. PMID- 1872053 TI - [Alfred Kantorowicz and his work in Istanbul]. PMID- 1872054 TI - [Orofacial manifestations of HIV-infection and AIDS]. PMID- 1872055 TI - [Infection prevention: common advice for the office team]. PMID- 1872056 TI - [Review of T-SCAN-systems for registration of occlusal condition]. PMID- 1872057 TI - [Taste disorders--an overview]. PMID- 1872058 TI - [Irreversible periodontal injury after treatment with Toxavit]. PMID- 1872059 TI - [GTR--technique--preparations, methods and results]. PMID- 1872060 TI - [Clinical studies of therapeutic results from ozonized water for gingivitis and periodontitis]. PMID- 1872061 TI - [Treatment of emergencies in dental practice--practical guide]. PMID- 1872062 TI - [Rehabilitation of dysgnathic patients from the patients' viewpoint]. PMID- 1872063 TI - [Guided tissue regeneration: fundamental advance in periodontology]. PMID- 1872064 TI - [Happy team workers--the best advertising]. PMID- 1872065 TI - [Comparative preparation of various cutting patterns for root tip resection]. PMID- 1872066 TI - [Virology of HIV]. PMID- 1872067 TI - [How expensive must a treatment room be?]. PMID- 1872068 TI - [Prevention--important preparation and accompaniments for caries-free therapy]. PMID- 1872069 TI - [Gingival reactions to mechanical irritation]. PMID- 1872070 TI - [Dental prosthesis--backward look and outlook]. PMID- 1872071 TI - [HIV and the immune system]. PMID- 1872072 TI - [Clinical experiments in filling therapy with composite inlays]. PMID- 1872073 TI - [Psychological influences on patients in the dental office]. PMID- 1872074 TI - [Efficacy of chlorhexidine digluconate and sanguinarine on plaque and bleeding index]. PMID- 1872076 TI - [Diagnosis of HIV infection]. PMID- 1872075 TI - [No resistance to orthodontic treatment? Empirical questioning of children and youth on adjustment to their orthodontic treatment]. PMID- 1872077 TI - [Full-porcelain bridge with InCeram technique in pouring experiment]. PMID- 1872078 TI - [Periodontal findings after gingival surgery for third molar extraction]. PMID- 1872079 TI - [Radiography diagnosis of cementum fibroma]. PMID- 1872080 TI - [Immediate poured prosthesis--a device for oral structure maintenance]. PMID- 1872081 TI - [Epidemiology, therapy and prevention]. PMID- 1872082 TI - [Dental and technical materials: trends]. PMID- 1872083 TI - [Hormone-dependent genital carcinomas]. PMID- 1872084 TI - [Serum and erythrocyte zinc, copper, magnesium and iron in women with normal pregnancies and pregnancy-at-risk (pregnancy-induced hypertension, fetal growth retardation and hepatosis)]. AB - In women with normal pregnancy and with pathological pregnancy (pregnancy-induced hypertension, fetal growth retardation, hepatosis) trace elements concentrations (Fe++, Cu++, Zn++, Mg++) were determined in serum and erythrocytes. The concentrations were partly decreased or increased in both serum and erythrocytes, but these changes were not significant. Thus, the analyses of trace element concentrations can not be used as a marker of the investigated pathological events of pregnancy. PMID- 1872085 TI - [Decrease in premature birth rate through consequent application of diagnostic and therapeutic standards in pregnancy monitoring]. AB - All pregnant women living in the district of Suhl have been observed in our prenatal outpatient department. All gave birth in our department for obstetrics and gynaecology. This observation is made on the base of a standard. From 1981 1987 there were 5,657 pregnant women with singleton pregnancies. In this time the rate of premature birth was on an average of 4.7%. But, over the time there was a slope from 7.3 to 2.8%. Consecutively there was a decrease of 50% in perinatal mortality. The successful standards for observation of pregnant women used in our department have been discussed. PMID- 1872086 TI - [Beta-endorphins during childbirth under transcutaneous electric nerve stimulation]. AB - Beta-endorphins are substances produced by the body to inhibit the perception of pain. Normally they exhibit a steep rise during birth. We have seen an impressive fall which also was statistically highly significant after the application of transcutaneous electric nerve stimulation in 20 parturient women. PMID- 1872087 TI - Serum 18:2 (9, 11) linoleic acid in normal pregnancy and pregnancy complicated by pre-eclampsia. AB - Serum 18:2 (9, 11) linoleic acid concentration was measured in normal pregnancy and pre-eclampsia. The 18:2 (9, 11) linoleic acid in normal pregnancy increased progressively with advancing gestation, reaching the highest value at the end of pregnancy. The 18:2 (9, 11) linoleic acid concentration in pregnancy complicated by pre-eclampsia was significantly higher than in normal pregnancy after week 28. It is suggested that measurement of the 18:2 (9, 11) linoleic acid concentration in plasma may be useful as a predictor of the likely development of pre eclampsia. PMID- 1872088 TI - [Problems in the therapy of intrauterine fetal growth retardation]. PMID- 1872089 TI - [IUGR--problems in diagnosis]. PMID- 1872090 TI - [Tomicide adsorption on bacterial cells]. AB - The capacity of the bacteriocin-like factor of tomicid being adsorbed on microbial cells, depending on the sensitivity of test microorganisms to the preparation, its form and concentration, the duration of the contact of microbial cells with tomicid, the temperature and pH of the incubation medium, was studied. The bacteriocin-like factor of tomicid was found to be capable of nonspecific sorption on microbial cells (in an amount of 64-128 units per mg of dried cell mass). The decrease of the temperature of the incubation medium to 0 degrees C and its pH to 4.8 and 5.4 inhibited the process of binding this bacteriocin-like factor by microbial cells. The presence of the substance with lysozyme properties in the preparation influenced the process of the adsorption of the main antibacterial component on microbial cells sensitive to lysozyme. PMID- 1872091 TI - [3 cases of viral carriage detected during screening for HIV antibodies]. AB - The results of screening more than 23,000 serum samples from persons belonging to risk groups, as well as those not belonging to such groups, in Moscow, Vilnius and Klaipeda are presented. Screening was carried out with the use of an assay system manufactured by the Scientific and Industrial Amalgamation "Antigen" (USSR). In this screening 3 HIV carriers were detected; of these, 2 were foreign students from two African countries. PMID- 1872092 TI - [The spatial structure and hierarchy of the ecological groups in the skin microbiocenosis of the breasts]. AB - In 120 nulligravidae, 175 pregnant women and 280 puerperants the skin microbiocenosis of mammary glands was studied. Its horizontal structure, the types of the distribution of different ecological groups over the surface of the biotope and their hierarchy, as well as the diversity of species at different anatomical areas, were described. The study showed that the representatives of resident flora were characterized by group distribution, while for transitory flora variations from occasional distribution in nulligravidae to group distribution in nursing mothers were noted. The most pronounced changes in hierarchy were observed in puerperants. In nursing mothers a significant increase in the diversity of species at different anatomical areas were also disclosed. PMID- 1872093 TI - [Streptococcus group B in a maternity home with a decentralized system of newborn infant care (of the mother-child type)]. AB - In a maternity hospital with the decentralized system of infant care the presence of the group B streptococcal colonization of puerperants (13.0 +/- 4.5%), newborn infants (25.0 +/- 4.4%) and medical staff (16.9 +/- 3.2%) was established. The strains isolated in this hospital belonged to 13 different serotypes and antigenic combinations with type 1 a/c dominating among them (28.7 +/- 4.8%). Group B streptococci were found to be transmitted by the vertical way in one out of two colonized mother-child pairs, in all other cases the nosocomial spread of streptococci occurred. PMID- 1872094 TI - [A mathematical model of the epidemic process in anthroponotic infection with stable and homogeneous factors]. AB - A very simple mathematical model of the epidemic process of human infection in the presence of stable and homogeneous factors has been created and analyzed. The theoretical possibility of describing the detailed course of the epidemic process by means of this model, permitting the consideration of inner parameters which cannot be determined in any other way, has been shown. The study has revealed that the approximation of the model to the real epidemic process is connected with the introduction of the notion of the heterogeneity of the parasite and host populations into the axiomatics of modeling. PMID- 1872095 TI - [Measures to prevent outbreaks of hospital infections]. AB - On the basis of the analysis of 69 outbreaks of hospital infections registered in the USSR in 1986-1989, as well as additional observations made by the authors, a number of factors which determined the present state of the problems concerning this kind of morbidity in the USSR were established: an insufficient level (in cases of enteric infections) or a low level (in cases of purulent septic infections) of etiological diagnosis; poor efficiency of the epidemiological investigation of outbreaks; defects in the work on the prophylactic detection of potential sources of infection among medical staff, parturient women or mothers taking care of their infants. Some possible solutions on these aspects were proposed. Cases of outbreaks of hospital infections among newborns were used as an example demonstrating that such outbreaks were caused mainly by breaches of antiepidemic and sanitary rules in respective hospitals; thus, in one-third of the cases of outbreaks such breaches were observed in maternity clinics with insufficient material and technical equipment. The prevention of these breaches is considered to be the main road to the solution of the whole problem of the prevention of epidemic outbreaks in hospitals. PMID- 1872096 TI - [Radioimmunological analysis in studying the persistence of the plague antigen in the body of rodents and ectoparasites in natural foci in Siberia]. AB - To study the persistence of Y. pestis capsular antigen, or fraction 1 (F1), in the body of less important plague carriers in the Mountain Altai and Transbaikal natural foci, as well as in experimentally infected ticks, the liquid-phase competitive radioimmunoassay (RIA) was used for the first time. In this study RIA showed, due to its sensitivity, doubtless advantages over traditional methods, such as the passive hemagglutination (PHA) test and the antibody neutralization (AN) test, and made it possible to detect F1 in picogram amounts. RIA revealed that F1 persisted in Siberian long-tailed gophers for up 14 months after the infection of the animals in diffusion chambers and for 7 months after their infection by subcutaneous injection. Experiments on Daurian pikas confirmed that, in comparison with the PHA and AN tests, RIA ensured fourfold effectiveness in the detection of antigen F1. The study of infected mites revealed that antigen F1 could be retained in them for more than a year and detected by RIA techniques in 10% of cases. The data obtained in this investigation indicate that the persistence of microorganisms should be studied mainly with the use of new generation tests, and RIA, being one of the most sensitive techniques, deserves wide approval and introduction into the practical work of institutions intended for plague control. PMID- 1872097 TI - [Changes in the humoral response to sheep erythrocytes based on data from a determination of the level and classes of antibodies in mice immunized with purified staphylococcal anatoxin]. AB - The intensity and direction of the modulation of humoral immune response, induced by the action of purified staphylococcal toxoid (PST), depend on the dose of the preparation, the dose of the test antigen, the scheme of the experiment, the time of the registration of its results and the genotype of animals. PST induces the modulation of the synthesis of both IgM and IgG antibodies. The injection of small divided doses of PST enhances immune response to heterologous antigen, while a single inoculation of the total dose produces no such effect. PMID- 1872098 TI - [The immunochemistry of the antigenic fractions of Clostridium tetani toxin]. AB - The localization of tetanospasmin and tetanolysin in C. tetani cells has been determined by the cytochemical method in the dynamics of the development of the microbial population. As shown in this investigation, tetanolysin, similarly to exotoxins, is released from microbial cells into the culture fluid mainly during the first 24 hours of cultivation, while tetanospasmin, similarly to endotoxins, is released only in the process of the destruction of these cells at the phase of the death of the microbial population. PMID- 1872099 TI - [The immunogenetic aspects of erysipelas infection]. AB - The distribution of the antigens of the HLA system in 517 erysipelas patients, constant residents of Voroshilovgrad and the adjoining region (the Ukrainian SSR), has been studied. The HLA system has been found to take part in the formation of predisposition to erysipelas and its clinical forms. Predisposition to erysipelas infection has a polygenic nature and is associated with antigens HLA-A2, B5, B12, Bw35. The specific features of HLA-A10, Aw12, B7, B8 have, seemingly, a protective character. The most pronounced connection between the disease and histocompatibility antigens has been detected in patients with frequent and multiple relapses of erysipelas. PMID- 1872100 TI - [The use of microdot immunoenzyme analysis with visual detection for the determination of tularemia antibodies]. AB - The possibility of using the micropoint enzyme immunoassay (EIA) on a nitrocellulose membrane with the visual evaluation of results for the detection of tularemia IgG antibodies in hamadryas baboons at the postvaccinal period has been studied. The sensitivity of this assay has been compared with that of the passive hemagglutination (PHA) test, the microagglutination (MA) test and EIA with the spectrophotometric evaluation of results in plates. As shown in this study, EIA in the above-mentioned modification can be successfully used for the detection of tularemia antibodies in the blood serum. The sensitivity of micropoint EIA has proved to be not inferior to that of EIA in plates, while exceeding the sensitivity of the PHA test 10- to 20-fold and the sensitivity of the MA test 10- to 1,000-fold. This method is simple, reliable, highly sensitive, economic and requires no special equipment, which makes it highly promising for the diagnosis of tularemia and the evaluation of humoral immunity at the postvaccinal period. PMID- 1872102 TI - [The production of antibody-producing hybridomas to the Lassa virus]. AB - The work deals with obtaining hybrid cell lines producing monoclonal antibodies to Lassa arenavirus. To obtain preparations for the screening of hybridomas by indirect immunofluorescence techniques, the dynamics of the accumulation of Lassa virus antigen in cell cultures Vero and 4647 was studied. The maximum accumulation of the virus antigen in Vero cells was shown to occur on day 3 after inoculation with a dose of 1.0 PFU/ml. The influence of different doses of gamma radiation on the infectious and antigenic activity of the virus was studied. The expediency of using a dose of 20.0 kGy for the irradiation of the virus was shown. The optimum schedule for the immunization of BALB/c mice was worked out, which made it possible to obtain activated mouse spleen cells used for the construction of hybridomas. The capacity of hybrid cells, injected into syngeneic mice, for the generation of tumors was shown. PMID- 1872101 TI - [The morphological characteristics of globulin production during the vaccinal process induced by tularemia and brucellosis vaccines]. AB - Significant data on the dynamics of globulin production in guinea pigs in the process of immunogenesis after the injection of Francisella tularensis vaccine strain or conjugated brucellosis vaccine have been obtained by means of immunofluorescence and the enzyme immunoassay. The number of globulin-producing cells in lymphoid organs (the spleen, regional and remote lymph nodes) differs, depending on the injected antigen. The relationship between the character of immunomorphological changes in lymphoid organs and the dynamics of the increase of antibody titers in the peripheral blood of the animals after their immunization with conjugated brucellosis vaccine and the injection of avirulent F. tularensis has been established. PMID- 1872103 TI - [New data on the chemical structure of lipopolysaccharides and the practical prospects]. PMID- 1872104 TI - [Long-term results of the Collona acetabuloplasty]. AB - The authors evaluate in their paper the long-term results of capsular acetabuloplasty by Colonna's method in the material of the First Orthopaedic Clinic, Faculty Hospital Bratislava. The mean time interval after operation was 20 years. The results are compared with previous evaluations made by Cervenansky and Kalman. Very favourable results were recorded in 3% of the patients, good results in 24%, satisfactory results in 39% and poor results in 39% and poor results in 34% of the patients. A marked shift towards unsatisfactory results is due to incorrect indication of acetabuloplasty which in the was a certain compromise, and also due to the surgical technique. The authors assume that correct and early prevention and treatment will eliminate capsular acetabuloplasty from the range of standard surgical therapeutic procedures in L.c.c. PMID- 1872106 TI - [The Bosworth method of acetabular roof plasty--long-term results]. AB - Operation of the roof of the acetabulum were performed in 1959-1979 at the First Orthopaedic Clinic in Brno in 110 patients. The authors checked 66 patients with 70 roofs during a mean period of 23 years (11-31 years) after operation. The mean age of the patients at the time of operation was 20 years. Forty-two patients were operated at the age of 14-30 years. The authors recorded 25 good, 23 satisfactory and 20 poor results. Sixteen patients were subjected to another operation. Poor results were observed in hip joints with marked incongruence (severe dysplasia, postluxation necroses), in patients with a wrong indication (instead of the roof osteotomy of the pelvis according to Salter or Pemberton should have been performed) and in cases where the wrong technique was used (roof too short or high-set). The best results were obtained in the age group from 14 25 years. The authors recorded a favourable effect of the operation still 31 years after operation. In patients with obvious secondary arthrosis after 15 years no favourable effect was found. The authors discuss different types of roofs derived from the original method of Spitzy, the range of indications, as compared with Chiari's osteotomy and compare the results with those of other local authors. PMID- 1872105 TI - [Scintigraphy in preparation for revision alloplasty of the hip joint]. AB - The author presents an account of the development of scintigraphic methods in the detection of inflammatory processes of the musculoskeletal system. The original method used in vitro 111In labelled separated leucocytes. It was improved by the possibility to label leucocytes by means of HMPAO 99mTc. In vivo leucocytes can be labelled by means of monoclonal antibodies. Nanocolloid offers similar possibilities as regards use and gives a good yield. Its use is simple and the preparation is available. Scintigraphy with nanocolloid must be considered nowadays the first scintigraphic method used when an inflammatory process is suspected, in particular of the extremities. Scintigraphy with nanocolloid can differentiate in planned revision alloplasty septic and aseptic loosening. The mentioned finding can be used for planning, implementation and ensuring the operation. The author was able, in collaboration with the department of nuclear medicine, to test scintigraphy with nanocolloid in five patients with complains after alloplasty of obscure origin. Patients' data are listed in table a and two cases are discussed in more details. PMID- 1872107 TI - [Neonatal osteomyelitis is still a reality]. AB - The authors draw attention to the fact that it is essential to consider osteomyelitis of children under 1 year as a separate nosological unit with regard to the anatomical features of the vascular supply of epimetaphyses. The authors discuss the diagnostic difficulties. In addition to the basic examination they emphasize also the importance of whole-body scintigraphy and examination by ultrasound. They indicate surgery where clinical symptoms do not recede within 24 48 hours after the onset of antibiotic treatment and where on probatory puncture pus is revealed and if during establishment of the diagnosis the X-ray finding is already positive. As to antibiotics they use Oxacillin first. The authors evaluate the results of treatment of 25 neonates after a 2-10-year interval following the onset of the disease. The process was found most frequently in the proximal and distal metaphysis of the femur (56%) and in the proximal metaphysis of the tibia (24%). They operated 18 patients in the acute stage (72%). Staphylococcus aureus was cultivated in 60% from pus and in 50% from haemocultures. The authors found a satisfactory state in 17 patients (68%) and an unsatisfactory one in 8 patients (32%). PMID- 1872108 TI - [Use of fluoroquinolone chemotherapy in orthopedics and traumatology]. AB - In the submitted review the authors analyze hitherto published results with the use of new antimicrobial chemotherapeutic drugs--fluoroquinolones in the treatment of infections of the bones, joints, soft tissues and also in the peroperative prophylaxis in orthopaedics and traumatology. Quinolones are one of the drugs of choice which may be successful in the treatment of staphylococcal and gram-negative chronic osteomyelitis which are resistant to classical treatment and also the drug of choice in the treatment of septic arthritis and ostitis. PMID- 1872109 TI - Iatrogenic stress fractures. AB - The author treated since 1982 85 fractures caused by overloading, incl. 19 which were associated with surgical, manipulation and medicamentous treatment. These iatrogenic influences altered statics and had a bearing on the locomotor stereotype causing deterioration of mechanical properties of osseous tissue and as a result of external rhythmic force during manipulation. Analysis of the causes makes it possible to draw preventive conclusions. PMID- 1872110 TI - [Distribution of transverse dimensions of the patella in the adult population. Relation to the development of the patellar component in knee joint prosthesis]. AB - The development and manufacture of the patellar component was associated with a more detailed osteometric investigation of the patella and evaluation of its range of sizes in our population. Evaluation of data 1042 probands (477 women, 565 men) proved: a) there are no significant lateral differences of transversal dimensions of the patella and femoral condyles; b) The mutual relationship of the above mentioned dimensions does not correlate, and thus no conclusions can be drawn from the transversal breadth of the condyles on the dimensions of the patella; c) The range of patellar diameters in the population is very wide, and to meet demands, it will be necessary to manufacture patellar components in cca five sizes. PMID- 1872111 TI - [Problems of recurrence and reoperations in discogenic lumboischiadic syndromes. 1]. AB - During the period between Feb. 1 1982 and Dec. 31 1989 at the Neurosurgical Clinic in Kosice 2346 patients were operated (813 women and 1533 men) on account of discogenic lumboischiadic syndrome. Because of true relapses 79 patients were reoperated (29 women, 50 men), i.e., 3.37% of 2346 patients. These formed the investigated group. The youngest patient was 18 years old, the oldest 60 years, the mean age was 38.5 years. Check-up examinations, X-ray material and mathematical evaluation revealed that even marked deviations from the ideal weight according to Broca, balneotherapy, regular physical training and localization of the damaged disc did not influence the development of a true relapse which called for re-operation. The latter were significantly more frequent in subjects engaged in excessively hard physical work and those who developed a complication during the first operation. PMID- 1872112 TI - [Problems of recurrence and reoperation in discogenic lumboischiadic syndromes. 2]. AB - In a group of 79 patients (29 women and 50 men) reoperated at the Neurosurgical Clinic of the Faculty Hospital with Policlinic in Kosice between Feb. 1 1982 and Dec. 31, 1989 for substantiated suspicion of a true relapse of discogenic lumboischiadic syndrome it was revealed that neither perimyelography nor CT examination of the spine disclosed reliably the conditions in the spinal canal. The assumed disc compression of spinal roots was confirmed by the surgeon on reoperation only in 58.2% of the patients. Complications were encountered on reoperation in 26.6% patients of the group whereby in the majority an injury of the dura mater fixed by an epidural scar was involved. The results of reoperations were worse than the results of primary operations. Improvement can be expected from a better differential diagnosis of complaints after disc operations and from improvement of the surgical technique which will reduce the risk of preoperative complications, e.g. by using the microsurgical technique. PMID- 1872113 TI - [Ice skater's fracture]. PMID- 1872114 TI - [Medial and lateral shift of the femoral head epiphysis]. AB - The authors demonstrate a developmental anomaly of the position of the epiphysis of the hip joint, i.e. its medial shift. They assumed that it will be a pre arthrotic condition, as other known dysplasias of the hip joint. However, the position was reversed as if the shift of the epiphysis of the head of the femur in a medial direction protected the hip joint from the development of arthrotic changes. In case of a medial shift of the epiphysis of the head of the femur- caput varum prearthrosis is not involved. PMID- 1872115 TI - [Intra-articular injection therapy]. AB - The author pays attention to intraarticular treatment of patients with articular affections in orthopaedics. He mentions briefly the pathophysiology of inflammatory rheumatic and degenerative articular affections, with the aim to draw attention to possible negative influences of intraarticular treatment. In two instances he describes cortisonoid arthropathy in one case the development of iatrogenic purulent arthritis. The author emphasizes that intraarticular injection therapy, in particular corticoid therapy, is therapeutical very effective. However, side-effects of preparations have to be considered, in particular the development of arthropathy and pyogenic arthritis. Intraarticular treatment should be administered only by a doctor familiar with the anatomy, physiology and pathophysiology of the joint as well as with the pharmacological effect of the administered preparation in order to influence the pathological process without or with minimal side-effects. If intraarticular treatment fails, if there are indications of side-effects, it is important to seek further possibilities of conservative and in particular surgical treatment. PMID- 1872116 TI - [Use of the Volkov-Oganesjan distraction-reposition apparatus in treatment of flexion contractures of the interphalangeal joints]. AB - In the submitted paper the authors present their experience with the treatment of flexion contractures by a Volkov-Oganesjan distraction reposition apparatus. The principle of treatment is continuous distension of shortened ligaments. The Volkov-Oganesjan apparatus makes systematic rehabilitation of the joint possible during gradual reposition of the contracture and at the same time prevents damage of the articular cartilage. The group comprised six patients who were treated and followed up. In four a post-traumatic condition was involved, once burns caused by electric current, and in one patient reoperation of a flexion contracture was involved. The mean grade of fixation of the PP joint before operation was 70 degrees. On average correction to 22 degrees was achieved. The mean period of treatment with the apparatus was 21 days. The therapeutic results was evaluated at least three months after removal of the apparatus. In all patients it proved possible to influence the flexion contracture by the method of an external fixation device. No complications of treatment were observed. The method and effect of therapy are consistent with the conclusions of work in vitro concerned with the role of traction in the shaping of ligaments. PMID- 1872117 TI - [Penetration of antibiotics into the intervertebral disk]. AB - The role of antibiotics in the treatment and prevention of postoperative spondylodiscitis is still controversial. In a group of 15 patients operated on account of lumbar discopathy, the authors investigated the penetration of antibiotics into the intervertebral disc, in correlation to serum levels, when antibiotics were administered during operation. Despite high serum levels rolitetracycline was not detected in extirpated material of the disc, gentamycin reached 2-6% serum levels. The authors give an account of views on the role of antibiotics in the prophylaxis of postoperative spondylodiscitis and recommend their administration in particular in risk groups. They recommend antibiotics in case of early diagnosis of postoperative spondylodiscitis, in the later stages of the disease the role of antibiotics is controversial. PMID- 1872118 TI - Oxytocin influences preovulatory follicular development and advances ovulation in rats. AB - Oxytocin has been shown to advance gonadotropin secretion in pro-estrus rats. The effects that oxytocin-induced changes have on the ovary were investigated in this study. Oxytocin administered to rats at proestrus 09.00 h, 10.00 h and 11.00 h advanced follicular growth, progesterone secretion, and the time of ovulation. However, both treated and control groups of rats ovulated similar numbers of oocytes and the oocytes released were of similar fertility. Because oxytocin has been shown to induce early LH and FSH release the effects of oxytocin administration on the ovary were possibly an indirect action involving the pituitary. The results of this investigation indicate that exogenous oxytocin alters the timing but not the fertility of periovulatory events. PMID- 1872119 TI - Alterations in the morning plasma levels of hormones and the endocrine responses to bicycle exercise during prolonged strain. The significance of energy and sleep deprivation. AB - The relative significance of physical exercise, energy and sleep deprivation for the morning levels of hormones and the endocrine response to short-term bicycle exercise were investigated in 24 male cadets during a 5-day military training course. Significant increases in the morning levels of noradrenaline, adrenaline, and dopamine, and a decrease in PRL were ascribed mainly to physical strain. Cortisol and hGH increased, whereas insulin and glucose decreased mainly due to energy deficiency. Pulse rate after the bicycle test was unchanged and similar in all groups in spite of increased catecholamine responses. The increased catecholamine response was mainly due to physical strain. The cortisol response to the bicycle test was increased in all groups, and energy deficiency caused slower postexercise recovery. The incremental hGH response to the exercise test was unchanged in the energy-deficient subjects but abolished in the well-fed subjects. The results suggest that the endocrine responses during long-lasting exhausting strain were mainly due to physical exertion and energy deficiency, whereas sleep deprivation did not play any major role. PMID- 1872120 TI - The effect of human growth hormone therapy on GH binding protein in GH-deficient children. AB - Previous studies have described the close similarity of the GH binding protein to the liver membrane GH receptor. Since GH regulates its own liver receptors, we examined the effects of short- and long-term hGH therapy on GH binding protein in children with GH deficiency. Six GH-deficient children received their first hGH dose ever, and the pharmacodynamics of serum GH was followed for 12 h, along with measurements of GH binding protein activity. Over the first 6 h, serum GH and GH binding protein activity exhibited a parallel increase, followed by gradual decrease. At 8 h, some of the patients exhibited an apparent second peak in GH binding protein, despite the continuous decrease in serum hGH. During the period of hGH treatment, serum GH binding protein increased progressively over a period of 6 months. In a second uncontrolled group of 7 GH-deficient patients who had been treated with hGH for 30-36 months, GH binding protein activity was also significantly higher than pretreatment values. We suggest that the short-term pharmacodynamic changes probably represent the endogenous turnover of the GH receptor, whereas the elevated GH binding protein activity on hGH treatment may reflect up-regulation of the GH receptor. PMID- 1872121 TI - Increased urinary free cortisol and decreased serum corticosteroid-binding globulin in polycystic ovary syndrome. AB - The adrenal participation in the pathogenesis of polycystic ovary syndrome is still under debate. In order to reappraise androgen and glucocorticoid secretion in this disease, we measured serum androstenedione, dehydroepiandrosterone sulphate, total and free testosterone, sex hormone-binding globulin, LH, FSH, PRL, cortisol, corticosteroid-binding globulin, and urinary free cortisol in 45 women with polycystic ovary syndrome and 27 controls, subdivided in obese and normal-weight subjects. Androstenedione, total and free testosterone were significantly increased, whereas sex hormone-binding globulin tended to be reduced in patients with polycystic ovary syndrome compared with controls, reaching a significant difference between obese patients and matched controls. Free testosterone and sex hormone-binding globulin were significantly increased and reduced, respectively, in obese compared with normal-weight patients. Urinary free cortisol and serum corticosteroid-binding globulin were significantly increased (p less than 0.001) and decreased (p less than 0.005), respectively. Urinary free cortisol exceeded the upper limit of the normal range in 50% of our patients. No appreciable differences were found in PRL and cortisol levels. Besides confirming a hyperandrogenic state, our findings point to an overactivity of the hypothalamic-pituitary-adrenal axis with subsequent diminution of corticosteroid-binding globulin in polycystic ovary syndrome. They also indicate that urinary free cortisol is not a reliable index in differentiating polycystic ovary syndrome from Cushing's disease. PMID- 1872122 TI - Postoperative goitre recurrence rate in Turkey. AB - A study was conducted on the incidence of postoperative nontoxic goitre in 206 patients. The mean period of postoperative observation was 7.8 years. The recurrence rate was 30.7% in the 26 patients to whom thyroxine was administered regularly and at doses of 0.15 mg/day or more in the postoperative period, and 46.9% in the 32 patients who received thyroxine regularly at low doses (0.10 mg/day). In contrast, recurrence rate was 71.4% in the 49 patients in whom use of thyroxine was irregular and 81.8% in the 99 patients who received no thyroxine. The recurrence rate was markedly reduced in the patients who used thyroxine regularly at doses of 0.15 mg/day or more as compared with those who used it irregularly or not at all. It was concluded that in Turkey, where iodine deficiency is a major contributory factor of the prevalence of goitre, postoperative administration of thyroxine is necessary in order to reduce the postoperative recurrence rate. PMID- 1872123 TI - Decreased growth hormone response to growth hormone-releasing hormone in Turner's syndrome: relation to body weight and adiposity. AB - A decreased growth hormone response to various secretagogues has been described in Turner's syndrome, but the mechanisms responsible for this decrease are unknown. Seventeen prepubertal girls with Turner's syndrome (age 6.4 to 15.7 years; height -0.2 to -5.4 SD, bone age -3.7 to -0.3 SD; weight 93 to 169% of ideal body weight) underwent a stimulation test with GHRH (0.5 micrograms/kg). Plasma GH and prolactin were measured by radioimmunoassay from -30 to +120 min and insulin-like growth factor-I at time 0. These values were compared with those observed in lean children with constitutional short stature. Peak plasma GH after GHRH was 17.0 +/- 3.6 micrograms/l (mean +/- SEM), significantly lower (p less than 0.001) than in the short lean children (39.2 +/- 5.1 micrograms/l). In Turner's syndrome patients, the peak GH value was negatively correlated with the percentage of ideal body weight (r = -0.58, p less than 0.02) and of body fat (r = -0.59, p less than 0.02). Plasma prolactin levels in Turner's syndrome did not rise after GHRH and showed a normal circadian variation, from 8.0 +/- 1.0 micrograms/l at 08.30 h to 5.0 +/- 0.7 micrograms/l at 11.00 h (mean +/- SEM). Mean (+/- SEM) baseline plasma insulin-like growth factor-I concentrations was 0.88 +/- 0.14 kU/l, higher than in the short lean children (0.49 +/- 0.08 kU/l, p less than 0.05). We conclude that the decreased GH response to GHRH of girls with Turner's syndrome is related, at least in part, to their excess body weight and fat and is associated with higher IGF-I levels than in short lean children. PMID- 1872124 TI - Octreotide treatment in acromegaly: a comparison between pen-treated and pump treated patients in a cross-over study. AB - The effect of a schedule of three daily injections of 100 micrograms octreotide (pen treatment) compared with that of a continuous sc infusion of 300 micrograms/24 h on GH and IGF-I suppression, and other GH-dependent parameters was studied in 10 acromegalic patients in a cross-over study. Treatment was administered via a specially designed pen or a pump for 4 weeks. Following a washout period of a further 4 weeks, patients were switched to the other mode of delivery. Mean GH levels decreased from 26.2 +/- 4.7 to 9.9 +/- 3.1 mU/l (p = 0.007) during pen therapy and to 7.7 +/- 2.4 mU/l (p = 0.003) during pump treatment. IGF-I levels decreased from 75.6 +/- 9.5 to 42.0 +/- 9.3 nmol/l (p = 0.003) during pen treatment and to 32.5 +/- 2.5 nmol/l (p = 0.001) during pump treatment. There was a significant difference in IGF-I levels between pen and pump treatments (p = 0.03). In 7 patients the IGF-I levels normalized during pump treatment compared with 3 patients in the pen treatment group. There was no change in the free T4 index levels, but the free T3 index significantly decreased during therapy, without changes in plasma TSH. This study demonstrates that continuous infusion with octreotide results in a better control of GH oversecretion than the intermittent mode of delivery. PMID- 1872125 TI - Biosynthetic growth hormone changes the collagen and elastin contents and biomechanical properties of the rat aorta. AB - The biomechanical and biochemical properties of aortas from female rats treated with biosynthetic human GH (b-hGH) for 80 days were investigated. b-hGH was administered at a dose of 5 mg.kg-1.d-1. Treatment with b-hGH increased the body weight by 75% and the diameter of the aorta by 14% compared with the control group. The concentration of collagen and the relative amount of collagen type I were increased, and the concentration of elastin was decreased. Aortas from the b hGH-treated group showed increased extensibility in the regions corresponding to physiological load values (i.e. 100-200 mmHg), and increased stiffness in regions with higher load values. The increased extensibility at low load values corresponds well with the loss of elastin, and the increased stiffness at higher load values with the increase of collagen and relative increase of collagen type I. These alterations induced by the growth hormone treatment might influence the elasticity and recoiling properties of the aorta. PMID- 1872126 TI - Thyroid hormone as a biological amplifier of differentiated trophoblast function in early pregnancy. AB - Direct effects of T3 or T4 on the trophoblast function were investigated in vitro using an organ culture system of human placental tissues. Explants of trophoblastic tissues obtained from normal early and term placentas were cultured with or without graded doses of T3 or T4 for 5 days in a serum-free condition. Addition of T3 (10(-8) mol/l) resulted in the maximum increase in daily secretion of progesterone, estradiol-17 beta as well as hCG alpha, hCG beta, hCG and hPL by cultured early placental tissues. Increases in progesterone and estradiol-17 beta secretion caused by the addition of T3 were further augmented in response to concomitant addition of pregnenolone and testosterone, respectively, suggesting that T3 (10(-8) mol/l) enhances 3 beta-hydroxysteroid dehydrogenase and aromatase activity in the placenta. These stimulatory effects of T3 (10(-8) mol/l) on the trophoblast endocrine function were also found with the use of T4 (10(-7) mol/l). Addition of higher or lower concentrations of T3 or T4 gave attenuated effects. These results suggest that the optimal concentration of thyroid hormone is needed for it to exert its maximally stimulatory action on trophoblast endocrine function. Unlike early placental tissues, cultured term placental tissues did not respond to the addition of T3 or T4 with increased endocrine activity. Thus, the frequent occurrence of spontaneous abortion in early pregnancy during the state of hypothyroidism or hyperthyroidism may represent a direct consequence of inadequate thyroid hormone availability at the level of placental trophoblasts, followed by diminished expression of trophoblast endocrine function. PMID- 1872127 TI - Ectopic pituitary transplants restore immunocompetence in Ames dwarf mice. AB - This work was undertaken to study the effects of prolactin on immune function in Ames dwarf mice. For that purpose, adult Ames dwarf mice were implanted with pituitaries from normal mice under the kidney capsule. Ectopic pituitary transplants produced the expected increase in plasma prolactin levels in male and female dwarf mice as compared to sham-operated dwarf or untreated normal mice. Body weight was significantly increased in pituitary-grafted dwarf mice of both sexes, but did not reach the values found in normal (non-dwarf) animals. Pituitary transplants induced an increase in thymus weight and in the number of lymphocytes in the thymus in dwarf mice of both sexes as compared to sham operated dwarf controls. The weight of the thymus in grafted dwarf mice remained below values found in normal mice, while the number of thymic lymphocytes became indistinguishable from those recorded in normal mice. Effects of pituitary transplants on the spleen were similar to those described for the thymus; however, neither the weight nor the lymphocyte number in pituitary-grafted dwarfs reached the values found in normal animals. Natural killer activity of spleen lymphocytes from pituitary-grafted male and female dwarf mice was greatly enhanced as compared to lymphocytes from sham-operated dwarfs. This effect was greater in males than in females. The number of white blood cells in pituitary grafted male dwarf mice was increased and indistinguishable from the values found in normal males. Surprisingly, this effect was absent in the females. These findings suggest that hormones secreted by the transplants, most likely prolactin and growth hormone, can enhance the immune response. This action may be mediated by direct action of prolactin and/or growth hormone on immune cells or by indirect effects. PMID- 1872128 TI - Beneficial effects of GH replacement therapy in adults. AB - Growth hormone deficiency in adults is associated with psychosocial maladjustment, reduced muscle strength, and reduced exercise capacity. Body composition is significantly altered, with increased fat and decreased muscle volume as compared with healthy subjects. Kidney function is subnormal. Epidemiological data suggest premature mortality owing to cardiovascular disease in hypopituitary patients. Short-term GH treatment trials have shown improved psychosocial performance, normalization of body composition, increased muscle strength, improved exercise capacity, increased cardiac performance, and normalization of kidney function. Thus GH replacement therapy in GH-deficient adults exhibits potential long-term beneficial effects. A number of important questions have to be addressed before long-term GH replacement therapy in GH deficient adults can be considered on a routine basis. PMID- 1872129 TI - Heterogeneity of human luteinizing hormone. Hydrophobic interaction chromatographic fractionation of some preparations. AB - The heterogeneity of human luteinizing hormone was investigated with high performance hydrophobic interaction chromatography on a TSK phenyl-5PW column using an ammonium sulphate gradient. Recovery of individual subunits, expressed as immunochemical activity, was in the order of 90%. Recovery of the intact hormone was less, approximately 25%. The technique appeared to be independent of the charge heterogeneity of the individual subunits. Each component as obtained by hydrophobic interaction chromatography showed considerable charge heterogeneity when studied by subsequent isoelectric focusing. Nonetheless, all chromatography fractions derived from either subunit showed the same collection of isoelectric values, quantitatively only differences for the beta-subunits could be detected. Heterogeneity of the individual subunits was clearly demonstrated after incubation of the preparations at 37 or 56 degrees C. The heterogeneity of the beta-subunit observed after incubation at 56 degrees C was different to the heterogeneity after incubation at 37 degrees C. After incubation at 56 degrees C, an additional component, with a longer retention time, developed directly from the intact molecule. The component is unstable and is transformed to one of the components detected also after incubation at 37 degrees C. Based on these results the existence of two populations of intact LH molecules with respect to their thermal stability is hypothesized. PMID- 1872130 TI - Human recombinant interleukin 1 inhibits TSH-stimulated morphological changes in thyroid follicles cultured as semi-organs. AB - To study the effects of human recombinant interleukin-1 on thyrocytes, we cultured thyroid follicles as semi-organs, each consisting of approximately 10-20 follicles, in the presence or absence of IL-1 alpha or beta. Semi-organ culture reproduces the in vivo environment well. After culture for 2 or 4 days, the follicles were incubated with TSH (10 U/l) for 4 h and fixed for light and electron microscopical examinations. Regardless of the presence or absence of IL 1, follicular structure, polarity, and luminal colloid did not change during culture. In thyroid epithelial cells cultured without IL-1, TSH markedly induced elongation of microvilli and formation of reabsorbed colloid droplets. On the other hand, both IL-1 alpha and beta inhibited these TSH-stimulated changes. The degree of inhibition correlated with the concentration of exposure to IL-1. We conclude that IL-1 inhibits TSH-stimulated morphological changes in thyroid follicles cultured as semi-organs, depending on the concentration of IL-1. PMID- 1872131 TI - Endocrine and metabolic effects of life-long food restriction in rats. AB - The effects of chronic (40%) food restriction from 6 weeks of age were studied in 28-month-old male Fischer-344 rats; the results were compared with ad libitum fed, old and young male rats at 28 and 3 months of age, respectively. Pituitary luteinizing hormone was similar in all old rats and was significantly lower than in young rats. In old ad libitum-fed, but not in food-restricted rats, serum levels of LH, testosterone and T4 were significantly lower than in young rats. Serum levels of T3 did not differ between young and old rats. Type-II 5' deiodinase activity in brown adipose tissue was similar in both groups of old animals and was significantly depressed as compared with that in young rats. Serum levels of triglycerides were significantly depressed in food-restricted rats, but were significantly increased in ad libitum-fed rats as compared with young rats. Both groups of old rats had significantly elevated serum levels of cholesterol over that in young rats, but the level was significantly lower in food-restricted as compared to ad libitum-fed animals. The results are consistent with the notion that life-long food restriction tends to preserve the activity of many metabolic functions. PMID- 1872132 TI - Topical indometacin, a prostaglandin inhibitor, in acute anterior uveitis. A controlled clinical trial of non-steroid versus steroid anti-inflammatory treatment. AB - Forty-nine patients were included in a controlled clinical trial comparing the effect of topical non-steroid versus potent steroid preparation in acute anterior non-granulomatous uveitis. Twenty-five patients were randomized to 1% Indometacin and 24 patients to 0.1% Dexametason treatment 6 times a day. There was no difference between the two groups initially. After 7 days of treatment we found significantly less inflammation in the steroid treated group, this significant difference disappearing on day 14. We conclude that whenever adverse reactions to corticosteroid eye drops are suspected or proven, Indometacin eye drops make up a useful alternative to even strong solutions of steroids. The study was carried out in the following practices: L. Ahrendt, L. Damgard-Jensen, P. Eldrup Jorgensen, J. Elmeros, H. Heuer, S. Jensen, M.H. Kjeldsen, P. Nellemann Sorensen, H. Petersen, N. Vedel-Jensen. PMID- 1872133 TI - High myopia with cone dysfunction. AB - All 3 children, 2 boys and 1 girl (the probands), in a family had high myopia and subnormal visual acuities. The boys had high myopia in both eyes, the girl had high myopia in 1 eye and low myopia in the other eye. Both of the boys had a protanomalous colour vision defect. The colour vision testing of the high myopic eye of the girl was not successful, the other eye had normal colour vision. In the electroretinogram examination, both cone and rod responses were decreased in 2 of the children. In the family study, results of an eye examination of 30 relatives were available. No other cases of high myopia or subnormal visual acuities were found. The father of the children, 1 of the paternal relatives, and 5 of the maternal relatives had low myopia. One maternal male cousin of the probands had a protanomalous colour vision defect. In the genealogical study, no relationship was found between the families of the father and the mother of the probands going back to the fifth generation. The heredity of this disorder is difficult to define. It could be autosomal dominant or recessive if the myopia only are taken into consideration. If the high myopias and cone dysfunction are considered to be parts of the same syndrome, the heredity could be x-chromosomal recessive or autosomal recessive. PMID- 1872134 TI - Electroretinographic studies of families with dominant retinitis pigmentosa. AB - Full-field electroretinograms were recorded from four different families with dominant retinitis pigmentosa. Two different types of the disease were recognizable and consistent within each pedigree, one with normal cone b-wave implicit times (one pedigree) and the other with prolonged cone b-wave implicit times (three pedigrees). The cone b-wave amplitude was found to decrease with age, but the implicit time did not, suggesting that the amplitude is useful for monitoring the progression of the disease whereas the implicit time seems more suitable for distinguishing different types of the disease. The progression rate was analyzed in a large pedigree, spanning six generations, three of which were examined in detail. The recently described Pro23His gene was not detected in the families. PMID- 1872135 TI - Plaques causing hemianopsia or quadrantanopsia in multiple sclerosis identified by MRI and VEP. AB - Four patients with definite multiple sclerosis (MS) gave evidence of demyelinating plaques that produced a form of visual loss atypical of MS, i.e. homonymous quadrantanopsia (women, 22 and 30 years), and homonymous hemianopsia (men, 30 and 42 years). Cerebral magnetic resonance imaging (MRI) identified areas with increased signal intensity situated corresponding to the observed visual field defects. The results of visual evoked potentials (VEP) were in accordance with what should be expected from anatomical considerations. PMID- 1872136 TI - Ultrasonographic, three-dimensional scanning for determination of intraocular tumor volume. AB - Important prognostic information may be gained from knowing the volume of intraocular tumors, such as choroidal melanomas. To measure such volume, we developed an ultrasonographic 3-D scanning system, which operates by an axial, back and forth, half-turn rotation of a commercial sector scanning transducer, applied directly onto a closed eyelid. Control of movement, data acquisition, and image analysis are accomplished by means of a microcomputer and application specific software. The elapsed time for scanning and digitizing 11 cross sectional images across a human eyeball, is 4 sec. Outlines of specific structures are traced manually. The system was tested through repeated, in vitro measurements of known volumes of meat; the mean variation coefficient of these measurements was 2.8%. While accurate estimates were obtained on volumes between 0.01-0.25 ml, these are linearly dependent on gain setting. A patient with a choroidal melanoma was scanned repetitively. The procedures of scanning and tracing contributed about equally to the total variance. This method of scanning allows repeatable, reliable, and easily generated measurements of a tumor's volume and, thus, has great potential for use in the diagnosis and treatment of malignant, intraocular tumors. PMID- 1872137 TI - Lens autofluorescence in healthy individuals. AB - We measured blue-green autofluorescence (AF, 495 nm/520 nm) of the lens in 43 random eyes of 43 healthy volunteers aged 6-86 years, five in each decade, using an instrument designed by one of us (HN). The instrument generates an autofluorescence profile, which consists of anterior and posterior juxtacortical peaks and a central plateau. The height of the anterior peak was taken as a maximum autofluorescence value and the square root of the ratio between the posterior and the anterior peak was used as a lens transmission index. The coefficient of variation for the measurement technique was 3.9% for maximum autofluorescence and 2.9% for lens transmission index. Both the maximum autofluorescence and the transmission index were highly correlated with age. Statistically over 90% of the variation in maximum autofluorescence values and almost 70% of the variation in transmission could be attributed to age. PMID- 1872138 TI - Eyelid complications in trachoma: diagnosis and management. AB - We present our experience (at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia) with the management of the trachomatous eyelid disease. Four major eyelid complications: cicatricial entropion, eyelid retraction, secondary blepharospasm and brow ptosis, are described and their management outlined. Nine hundred sixty patients with cicatricial entropion are presented with thorough discussion of the surgical procedures and results. The surgical management of eyelid retraction, blepharospasm and brow ptosis is geared to provide the ophthalmologist with a complete overview of the disease pattern. PMID- 1872139 TI - Senile changes of crystalline lens: effects on the delayed latency of pattern visually evoked potentials in phakic and pseudophakic eyes. AB - We recorded visually evoked cortical potentials to pattern stimuli (PVECPs) in 22 patients who received a posterior chamber intraocular lens implant. The mean latency of the P100 obtained from patients was not significantly different from that of age-matched normal phakic subjects. Furthermore, we found that both groups showed a similar increased delay of the P100 latency with age. The results of this study indicated that the senile opacity of the crystalline lens does not contribute to changes of PVECPs with age. These alterations may be due to senile changes of the neural pathway. PMID- 1872140 TI - Long-term follow-up of baseline learning and fatigue effects in the automated perimetry of glaucoma and ocular hypertensive patients. AB - The detection of change in the visual field is confounded by factors associated with the patient response. Sixteen patients who had previously undergone a training regime in automated perimetry over a short time period were followed up to evaluate the longer term learning and fatigue effects. The patients, all attending a glaucoma clinic, were originally naive to automated perimetry. The training period had comprised examination of the right followed by that of the left eye with the Humphrey Field Analyser 630 on each of 3 successive days and again after an interval of 12 days. The follow-up study comprised two examinations on 2 successive days after a follow-up period of between 5 and 15 months (mean 8.7 months). The learning effects present over the initial training period were not observed at the follow-up whilst the fatigue effects in the fellow eye were still apparent. PMID- 1872141 TI - Occurrence of disc haemorrhages in open-angle glaucoma treated with pilocarpine or timolol. AB - 1573 examinations were performed on 397 eyes. hh was found in 55 eyes--thromboses included--at 91 examinations. Part of this material qualified for use in a comparative study with pilocarpine in 81 eyes and timolol in 82 eyes. The relative frequency of hh in the treated groups and in the pretreatment group was not significantly different from that of the whole material. No indication of pressure reduction with effect on the occurrence of hh could be detected. The average probability of hh at an examination chosen at random was 6 per cent in this material of ordinary simple and capsular glaucoma cases. The occurrence of haemorrhages in relation to age, sex, general hypertension and diabetes are discussed. PMID- 1872142 TI - Intraocular pressure 2 1/2 years after extracapsular cataract extraction and sulcus implantation of posterior chamber intraocular lens. AB - The intraocular pressure in 50 eyes of 50 patients was measured 2 1/2 years after planned extracapsular cataract extraction with intended implantation of a posterior chamber lens in the ciliary sulcus. The results were compared to the preoperative values, and the pressure observed after 4 months. Although a significant elevation was found from the fourth month (P = 0.015), the intraocular pressure at 2 1/2 years was found to be significantly lower than the preoperative value (P = 0.002). No significant difference was found in two subgroups in which transillumination defects in the iris or pigment in the lower anterior chamber angle was present. PMID- 1872143 TI - Morphology and proliferation of human corneal epithelium in organ culture. AB - Organ cultures of central and peripheral human corneal epithelium were maintained for 1 and 2 weeks in Hams F10 medium supplemented with 20% foetal bovine serum, and in medium conditioned by conjunctival epithelial cells. Light microscopy and scanning electron microscopy showed no obvious differences in morphology and survival between central and peripheral explants, or between explants cultured in conditioned and non-conditioned medium. Live cells and areas with confluent growth were seen in all types of explants. The results demonstrate that differences between growth of central and peripheral corneal epithelium in vitro do not necessarily reflect different proliferative potential in vivo. The previously reported lack of survival of central corneal epithelium in culture may reflect an insufficient in vitro system. PMID- 1872145 TI - Central and peripheral corneal thickness in newborns. AB - Central and peripheral corneal thickness was measured in 74 newborn children. The mean central corneal thickness was 0.573 +/- 0.052 mm. The mean peripheral thickness was 0.650 +/- 0.062 mm. There was no significant difference between right and left eyes, sex, gestational age or type of delivery. The central and peripheral corneal thickness in the first 24 h of life was significantly higher than after 48 to 72 h. The full-term babies with 2.500 to 3.000 g of birth weight had peripheral corneal thickness higher than the group with 3.501 to 4.000 g. PMID- 1872144 TI - Residual H2O2 compromises deswelling function of in vivo rabbit cornea. AB - The purpose of the study was to investigate the effect of H2O2 on corneal swelling, corneal deswelling and to determine the concentration of H2O2 in the aqueous humor. Four types of experiments were performed using the rabbit eye. 1. Central corneal thickness (CCT) measurements after instillation of H2O2 into the cul-de-sac and after wearing H2O2 soaked soft contact lenses (SLC) for 2 h using 60 ppm, 100 ppm and 300 ppm H2O2. 2. Measurement of corneal deswelling induced by wearing SCL and closed eye for 2 h. 3. Determining the H2O2 in the aqueous humor one h after instillation of H2O2 into the cul-de-sac. CCT increases of 7.5% and 10.7% were found after the instillation of 100 ppm and 300 ppm H2O2 into the cul de-sac. After wearing H2O2 soaked SCLs, CCT increased 4.6% and 5.8%, respectively. The H2O2 in the aqueous humor was 0.087 mM or a 160% increase after using 300 ppm H2O2. The increase in CCT and interference with the deswelling process is interpreted as a toxic effect on the cornea and an interference with the normal dehydration function of the endothelial pump. PMID- 1872146 TI - Central corneal thickness in premature babies. AB - Central corneal thickness was measured in 13 premature babies with a gestational age below 33 weeks. No difference was found between the thickness in the first and third post-natal week. At the age of 3 months the thickness had decreased significantly to the same level previously reported in full-term newborns. There was no correlation between gestational age, birth length and weight and central corneal thickness. PMID- 1872147 TI - Definition of normal macular thresholds on the Dicon AP2000 autoperimeter. AB - This paper presents the results of a study into the normal macular threshold measured by automated perimetry. The effect of age upon this parameter is demonstrated in a normal clinic population. A comparison is made with other age dependent tests of visual function and the clinical importance of the findings is discussed. PMID- 1872148 TI - A girl with Hermansky-Pudlak syndrome. AB - A young girl with ocular albinism and the Hermansky-Pudlak syndrome is described. Ocular albinism generally occurs in males. In this condition, the pigmentation of the skin and hair is nearly normal, and the melanin pigment abnormality is limited to the eyeballs. The chief complaints are visual disturbance, nystagmus, and photophobia. A 3-year-old girl was recently brought to our hospital with nystagmus, which she had exhibited since the age of 1 year. Funduscopy resulted in a diagnosis of ocular albinism. Further investigations, specifically, microscopy of her platelets, led us to conclude that she had Hermansky-Pudlak syndrome. PMID- 1872149 TI - Exophthalmos in myelodysplastic syndrome. AB - A case of myelodysplastic syndrome (MDS) who suffered alternating proptosis was reported. A 57-year-old Japanese man with MDS developed acute painful left proptosis with eyelid edema, conjunctival injection, visual disturbance, and restriction of eye movements. This lasted for 3 weeks. Computerized tomography (CT) showed swelling of the lateral and medial rectus muscles and the optic nerve, as well as a retrobulbar mass. Later, a similar painful right proptosis with severe conjunctival chemosis developed. CT showed only bilateral mild optic nerve swelling. The visual acuity of the right eye decreased to null even after remission of the proptosis. The patient died due to myocardial infarction and underwent autopsy. The right optic nerve stroma was found to be increased over that of the left. Cellular infiltration was noted in the left optic nerve and the retrobulbar connective tissue. This self-limiting and relapsing proptosis was apparently related to MDS. This is only the second MDS case with such severe ophthalmological symptoms reported in the literature. PMID- 1872151 TI - Scleral dellen or senile hyaline plaque? PMID- 1872150 TI - Bilateral metastatic endophthalmitis in diabetics. AB - A case of bilateral metastatic endophthalmitis in a diabetic patient is presented. Most cases from the literature are secondary to fungal sepsis, but few cases of metastatic bacterial endophthalmitis have been reported. In this diabetic patient urine and blood cultures were negative for fungi and positive for Escherichia Coli. The outcome was disappointing, the enucleation of both globes being necessary. The aim of the report is to outline that metastatic endophthalmitis should be counted among the possible complications of bacterial sepsis, especially in diabetics because of their susceptibility to infection. PMID- 1872152 TI - Electrically-induced osteogenesis in external fixation treatment. AB - This animal model experiment is performed to evaluate how bipolar direct current of 20 microamp. affects osteogenesis once external fixation treatment is applied in different forms: stabilization, distraction, and compression. In all cases a secondary healing, typical of external fixation treatment, was found; but a more mineralized callus and an increase in osteoprogenitor cell proliferation and differentiation were obtained through the use of electrical stimulation especially in the compression group. PMID- 1872153 TI - Girdlestone's pseudarthrosis after removal of a total hip prosthesis; a retrospective study of 40 patients. AB - In case of irreversible failed total hip replacement, a Girdlestone operation is sometimes the obvious solution: excision of cement and prosthesis without attempting a new hip replacement. Reasons for not implanting a new prosthesis are severe loss of bone stock, the risk of recurrent infection, or poor general condition. A clinical follow-up study was performed on 40 patients who underwent a Girdlestone hip procedure using the following criteria: pain, walking distance and the use of a walking support. The mean follow-up was 4.9 years. Postoperatively 33 of 40 patients had less pain compared with the situation before the operation. Sixteen patients walked more than 500 m, 13 patients walked 200-500 m and 11 patients walked less than 200 m, of whom 4 were wheelchair bound. The objective result was good in 40% of the patients, moderate in 42.5%, and bad in 17.5%. Subjectively 62.5% were satisfied. A Girdlestone arthroplasty after loosening of the hip prosthesis was a satisfying solution in most cases. PMID- 1872154 TI - [Considerations concerning the treatment of pseudarthrosis of the humerus]. AB - A humeral shaft fracture results in a nonunion in less than 10% of cases, regardless of the technique used. The treatment of such cases must be different from the initial treatment. In a pseudarthrosis of the medial shaft of the humerus with a transverse or short oblique line, a suitable procedure is medullary filling with Hackethal nails or a Kuntscher nail. If the fracture line is long and oblique, spiral, fragmented or distant from the narrow part of the humeral shaft, a modified interlocking intramedullary nail is recommended. PMID- 1872155 TI - The incidence of rotator cuff rupture. An anatomic study. AB - To evaluate the incidence of rotator cuff ruptures, we examined 122 autopsy specimens of the shoulder and compared our results with those reported in the literature. The incidence of partial tears in our study was 28.7%; the incidence of complete rupture was 30.3%. The frequency increased with age. We found no cuff rupture without supraspinatus tendon involvement. Very often, the cuff tear was bilateral. We do not share the opinion that the rupture of the rotator cuff is primarily an injury of men. We found a higher incidence in female than in male shoulders. PMID- 1872156 TI - A radiographical and biomechanical study of demineralized bone matrix implanted into a bone defect of rat femurs with and without bone marrow. AB - Repair of large bone defects represents a challenge to orthopedic surgery since autogenous graft is not available in large amounts. Demineralized bone matrix (DBM) which contains bone morphogenic protein, a potent osteoinductive glycoprotein, and collagen, an osteoconductive matrix, may be an effective substitute for these graft materials. Bone marrow which contains osteoprogenitor cells could potentiate the osteoinductive and osteoconductive properties of demineralized bone matrix. This study tested the ability of demineralized bone matrix with and without bone marrow to bridge large segmental defects, and evaluated the results both radiographically and biomechanically as compared to autogenous (isogeneic) cancellous bone graft. Demineralized bone-matrix segments implanted into a plated femoral segmental defect in rats resulted in firm union in most animals. Bone marrow significantly enhanced bone formation of demineralized bone-matrix implants at an early stage but with time, differences between bone marrow-augmented and bone marrow-deprived demineralized bone implants were no longer demonstrable radiographically and biomechanically. Newly formed bone had about 50% of the strength of the contralateral control bones. Femurs implanted with cancellous bone isografts had similar evidence of absolute union rate, radiographic and mechanical properties as DBM-implanted femurs. PMID- 1872157 TI - Patellar wear patients in total knee replacements. AB - In revising knee replacements 3 wear patterns have been noted; severe single facet wear which only occurs when the patella is dislocated or severely tilted, mild single facet wear from contact with the trochlear groove, and double facet wear. Double facet wear can occur when the knee flexes to more than 105-110 degrees, the edges of the patellar component then making contact with the edges of the femoral condyles across the cruciate gap. This double facet wear is potentially serious and may result in the patellar component wearing through. PMID- 1872158 TI - [Stable elastic nailing applied to diaphyseal fractures of the forearm in children]. AB - Elastic stable intramedullary nailing is the ideal internal fixation in children; the technique is not aggressive and the physiological periosteal consolidation is respected. This treatment is complementary to the conservative approach. The authors report their experience in 20 patients, aged 4 to 17 years. Primary instability (16 cases) and repeated fractures (3 cases) were the main indications. The operative technique is described. Open reduction was necessary for one or both forearm bones in 9 children. There were technical problems, but without consequences for the consolidation, which was always complete after 2 1/2 months, without cast immobilization. In all patients, the function was normal after 2 months. There were no serious complications. The fixation material should not be removed during the first postoperative year, in order to prevent refractures. PMID- 1872159 TI - Arthroscopy wounds: to suture or not to suture. AB - The arthroscopic wounds of 100 Caucasian patients were either sutured or simply bandaged on a random basis. The patients were reviewed after 2 and 12 weeks to ascertain the outcome of the two techniques. Suturing an arthroscopic wound resulted in an increased incidence of hematomas and superficial abscesses. A sutureless technique probably favors early hematoma draining, thus removing a potential cause of infection. PMID- 1872160 TI - Cartilage changes in rats induced by papain and the influence of treatment with N acetylglucosamine. AB - Cartilage damage in the knee joints of rats was induced with a single intraarticular injection of 10 mg papain. Such damage was indicated by a decrease in the content of glycosaminoglycans and histologically detectable alterations in the surface of patellar cartilage. Daily treatment of the rats with N acetylglucosamine by gavage led to an increase of the glycosaminoglycans of the cartilage and of incorporation of the radioactive precursor of glycosaminoglycan synthesis, 3H-glucosamine hydrochloride, in comparison to control animals treated with saline. The incidence of pathological alterations of the cartilage in histological samples was reduced. PMID- 1872161 TI - Treatment options for basicervical fractures of the femoral neck. A clinical follow-up. AB - Forty basicervical fractures of the femur were treated operatively. Local complications were recorded in 8 cases. In this mostly geriatric group of patients only 18 patients were alive after a mean follow-up of 63 months. Five of the 19 hips showed excellent results. Eight hips were evaluated as poor. No radiological signs of osteonecrosis were observed. Only one nonunion and one delayed union were noted. Surprisingly, the rigid nailplate (ASIF, Jewet) fixation appeared superior to the more up-to-date means of fixation, i.e. the dynamic hip screw. Although the material is limited and heterogenous owing to the relatively few numbers of basicervical fractures in the large entity of the femoral neck fractures in general, this difference was obvious and merits technical consideration. Due to its conical shape the dynamic hip screw is most obviously unstable in rotary stresses, and an additional cancellous screw would probably solve this problem. Some fractures of the series were treated by multiple pins, hemiarthroplasty or Ender nails. The number of cases so treated was small, but still notable for local complications. Thus it remains questionable whether these methods would result in a better response even with more common clinical use, when this special entity of femoral neck fractures is considered. PMID- 1872162 TI - Reconstruction of the metacarpophalangeal joint with a free vascularized metatarsal head. PMID- 1872163 TI - [Essential bone cysts of the calcaneum. Apropos of a case]. PMID- 1872164 TI - Intermittent priapism in spinal stenosis. AB - A case of intermittent priapism with neurogenic claudication caused by spinal stenosis is reported. The symptoms disappeared completely after decompressive laminectomy. PMID- 1872165 TI - [Fracture-avulsion of the anterior tibial tuberosity in adolescents]. AB - A rare case of a 14-year-old girl with an avulsion-fracture of the tibial tuberosity is reported (type III-A). This lesion is described mainly in boys. The authors explain the classification of the different types of avulsion fracture according to the epiphyseal development of the upper end of the tibia and the stage of maturation at the time of trauma. PMID- 1872166 TI - Proximal tibio-fibular synostosis. A rare congenital anomaly. AB - A case of proximal tibiofibular synostosis is presented along with a review of the literature. The variety of presenting complaints is discussed and the syndrome is compared with that of radio-ulnar synostosis. Possible modes of treatment are explained. PMID- 1872167 TI - [Congenital pseudarthrosis of the clavicle. Apropos of a case report and literature review]. AB - A new case of congenital nonunion of the clavicle is reported with a histological description. Medullar drilling and bone grafting "in loco" was performed during the surgical procedure. The etiologic hypotheses are discussed. The authors compare congenital nonunions between the pathologies associated with the necessity of medullar drilling for consolidation. PMID- 1872168 TI - [Acute hematogenous osteomyelitis due to ordinary germs in children with closed injuries. Study of a series of 44 cases]. AB - The retrospective study of a series of 44 cases of acute hematogenous osteomyelitis in infants and children has shown that 16 out of the 44 patients (36%) have a history of previous trauma at the site of bone infection. Seven infants were less than one year of age. For the remaining 37 children the incidence of previous local trauma rose to 43% (16/37). This incidence is similar to that in previous studies. Acute hematogenous osteomyelitis follows blood-borne spread of a pathogen from a portal of entry. Why hematogenous infection selects a particular bone is an enigma. Trauma has been said to predispose to the localization of infection but the association between trauma and hematogenous osteomyelitis is only found in one-third of the cases in both this study and in previous series. However these cases with a history of local trauma raise questions regarding the concept of "locus minoris resistentiae" and its medicolegal consequences. PMID- 1872169 TI - Intracompartmental pressure in the lower extremity after arthroscopic surgery. AB - We measured the intracompartmental pressure of 53 patients in the anterior, lateral, and dorsal compartments of the calf after arthroscopic procedures. Prior to making these measurements we established normative data in 80 healthy volunteers in a lying, sitting, and standing position. After short procedures like lavage, partial meniscectomy, removal of loose joint bodies, and shaving, we documented nearly normal pressures. We did the same in lateral release. In time consuming procedures like total synovectomy or ACL-reconstruction, especially if dorsal portals were used, we found a significant increase in intracompartmental pressure. In one patient the pressure even increased up to 55 mmHg. PMID- 1872170 TI - The risk of X-ray examinations of the lungs in neonates. AB - X-ray examinations of the lungs is an important element in the evaluation of the neonates and their respiratory function. It is often necessary to perform a large number of X-ray examinations depending upon the infant's birthweight, gestational age and respiratory problems. To estimate the risk of X-ray examinations of the lungs the radiation dose to 18 infants at the Neonatal Intensive Care Unit, Hvidovre Hospital, was measured by means of a thermoluminescent dosimeter placed on the nipple of the infant. The radiation dose to various organs was estimated and the risk weighted whole body radiation dose calculated to 40 microsievert per examination (AP- and lateral). Using the latest increased risk factors this means an excess cancer mortality of 5 x 10(-5) for boys and 11 x 10(-5) for girls per millisievert, corresponding to 25 X-ray examinations (AP- and lateral) of the lungs. It is concluded, that even using the latest increased risk factors, the radiation risk of repeated X-ray examinations of the chest in prematures will be very low considering the benefit for the infant. PMID- 1872171 TI - Development of early and late brainstem conduction time in normal and intrauterine growth retarded children. AB - Development of early (I-III) and late (III-V) brainstem conduction time (BCT) in the brainstem auditory evoked responses was examined and compared in 178 appropriate-for-gestational-age (AGA) and 24 small-for-gestational-age (SGA) children from birth to 6 years of age. In AGA children, the III-V/I-III interval ratio increased with age from birth to 2 years and remained relatively steady. This indicates that the development of the early and late BCT, or probably the lower and upper brainstem is not synchronous during early childhood, with a slightly faster development of the early BCT relative to the late BCT. In SGA children, the I-V, I-III and III-V intervals showed similar developmental trends to those in AGA children. However, the III-V/I-III ratio followed a developmental course which differed remarkably from that in AGA children. The ratio decreased slightly with age up to 2 years and was consistently smaller than in normal children after 1 year, indicating that the relative development of early and late BCT deviates from normal. This finding suggests that prenatal factors responsible for intrauterine growth retardation could alter the late or long-term development of the nervous system, resulting in sub-optimal outcome. PMID- 1872172 TI - A prospective study of acute diarrhoea in Finnish children from birth to 2 1/2 years of age. AB - To determine the incidence, clinical significance and etiology of acute diarrhoea in early childhood, a cohort of 336 children were followed from birth to the age of 24-32 (mean 26) months. More than half (55%) of the children had no diarrhoea, 26% had one episode and 19% had two or more episodes of diarrhoea during follow up; altogether 248 episodes of diarrhoea were detected. Rotavirus was by far the most common (26%) identified pathogen; adenoviruses were detected in 4% and bacterial pathogens (EPEC, Salmonellae, Yersiniae) in 4% of the cases. Two thirds of the episodes remained etiologically unresolved. Rotavirus diarrhoea was significantly more severe than diarrhoea due to other causes; 75% of severe episodes of diarrhoea were associated with rotavirus. About two thirds of the infants were breast-fed over 6 months; breast-feeding for less than 6 months was associated with a higher incidence of rotavirus diarrhoea between 7-12 months of age but not thereafter. About three quarters of the children were cared for at home beyond 12 months of age; those at home had a lower rate of rotavirus diarrhoea than those at day-care centers. PMID- 1872173 TI - Linear growth in children with cystic fibrosis. I. Birth to 8 years of age. AB - The linear growth of Swedish children with cystic fibrosis (CF), is described using the infancy-childhood-puberty (ICP) growth model. Length/height was studied in 51 patients during their first 8 years of life. The median age at diagnosis was 0.4 years (range 0.0-6.1 years). At birth, their mean length was close to normal, but the gain in length over the first 0.25 years of life was significantly below normal, resulting in a mean length SDS of -1.3. Length remained subnormal up to 1.0 year of age. Thereafter, catch-up growth occurred, resulting in almost normal height (mean SDS-0.3) at 5.0 years of age. Between 5.0 and 8.0 years of age growth was normal. The mean age at onset of the childhood component was not significantly different from the controls. Hence, the catch-up growth did not occur until after the onset of the childhood component. This study shows that the postnatal linear growth rate is retarded in children with CF during the first months of life. This is almost completely compensated for by a supranormal growth rate that starts at the end of the first year of life. PMID- 1872174 TI - Pseudomonas septicaemia in apparently healthy children. AB - Among 27 cases of Pseudomonas septicaemia in the Department of Paediatrics of Queen Mary Hospital from 1981 to 1988, we have identified 10 children without known predisposing causes before presentation and report their clinical features. Six were infants, of whom 4 developed shock on admission and died. Ecthyma gangrenosum was present in 4 patients. Pseudomonas aeruginosa was isolated in 8 patients. All isolates, except Ps. cepacia, were sensitive to gentamicin. One patient had cyclical neutropenia. Another had an appendicular abscess. Salmonella was cultured from the stool in one patient. Although Pseudomonas septicaemia is normally considered to be associated with underlying immunodeficiency, in 22% it occurred in previously healthy children. Mortality is high especially in infants who develop septicaemic shock. It is advisable to cover for Pseudomonas septicaemia with aminoglycosides or ceftazidime in sick septic infants. PMID- 1872175 TI - Urinary C-peptide excretion in obese and anorectic children. AB - To assess the total insulin secretion in children in different nutritional states we have analysed the 24 h urinary C-peptide excretion in 32 obese children (16 boys and 16 girls) 8-15 years of age as well as in 7 girls with anorexia nervosa 11-16 years of age. Obese children had a median urinary C-peptide excretion rate of 0.27 nmol/kg/24 h, which was not different from that of a group of normal weight children. In the group of anorectic girls, on the other hand, the median value 0.47 nmol/kg/24 h was significantly (p less than 0.05) higher than for normal-weight girls of the same age (median = 0.26 nmol/kg/24 h). These results indicate that in obese children insulin secretion, measured as the 24 h urinary C peptide excretion per kg body weight, is the same as in normal-weight children. Total insulin secretion is consequently increased. In anorexia nervosa, on the other hand, the higher C-peptide excretion per kg body weight compared with normal-weight children, indicates that insulin secretion is increased in relation to body weight. PMID- 1872176 TI - Utilization of primary care versus specialized care in children with and without chronic illness. A population-based study. AB - Children's utilization of curative care was studied to analyse the division of responsibilities between undifferentiated primary care and specialized care. All chronically ill (n = 510), a control group (n = 287) and the total population 0 15 years of age (n = 6080) in a primary care district were studied using register data. Chronically ill children comprised 8.4% of the total child population and were registered for 1/10 of the primary health care visits, 1/3 of the specialized visits, 1/3 of the hospitalizations and 1/2 of the in-patient days of all children. The yearly ambulatory visits were 3.7/child in the chronically ill and 1.5/child in the control group, of which 1/3 and 2/3, respectively, were to primary care. Utilization of specialized care increased with disability. Chronically ill children visited primary care mainly for acute respiratory infections but seldom for allergic or other chronic conditions. PMID- 1872177 TI - Long-term pulmonary sequelae in low birthweight infants with and without respiratory distress syndrome. PMID- 1872178 TI - Outcome of rehydration of diarrhea cases by oral route. PMID- 1872179 TI - Changing pattern of coeliac disease in western Toscana. PMID- 1872180 TI - Mercury vapor poisoning associated with hyperthyroidism in a child. PMID- 1872181 TI - Priapism in a child with acute lymphoblastic leukemia. PMID- 1872182 TI - Enalapril in children with congestive heart failure. PMID- 1872183 TI - X-linked agammaglobulinemia and isolated growth hormone deficiency. AB - No further reports of associated X-linked hypogammaglobulinemia and isolated growth hormone deficiency have appeared in the literature since the description of the first affected family, two brothers and two maternal uncles, by Fleisher et al. in 1980. We report here a 13-year-old boy with X-linked agammaglobulinemia and isolated growth hormone deficiency, also probably inherited as an X-linked trait. The height of an older agammaglobulinemic brother who died at 6 years of age was below the third percentile. PMID- 1872184 TI - Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD syndrome). A clinical study in two Sudanese families. AB - Four Sudanese children with DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) are reported. They were two boys (aged 15 and 16 years) in one family and a boy and a girl (aged 16 and 6 years, respectively) in another family. Diabetes mellitus was first to appear (at 3-8 years) followed by deafness and visual failure; and the disease ended fatally in one patient (aged 20 years). In the other three, diabetes insipidus was confirmed using water deprivation test for 8 hours. The maximum urine osmolality ranged between 131-523 mOsm/kg, whereas the corresponding plasma osmolality ranged between 315-332 mOsm/kg. Slight further improvement in urine concentration was observed in 2 of the patients following the use of desmopressin (DDAVP, 20 micrograms intranasally). Intravenous pyelography, voiding cystourethrography and ultrasound revealed severe bilateral hydronephrosis, dilated ureters and distended bladder without vesicoureteral reflux in the three patients. With the high rate of consanguinity prevalent in North Africa and the Middle East, we recommend examining children who present with diabetes mellitus in this region for features of DIDMOAD syndrome. PMID- 1872185 TI - Iron and infection. PMID- 1872186 TI - Is it time for Europe to reconsider newborn circumcision? PMID- 1872187 TI - Plasma amino acids in adolescents and adults with phenylketonuria on three different levels of protein intake. PMID- 1872188 TI - [HPC purity tests for caffeine, theophylline and theobromine]. AB - After giving a survey of the literature of the HPLC methods for the determination of caffeine, theophylline and theobromine two methods are presented for their purity test, i.e. their detection in each other at the trace level. In the reversed-phase system the stationary phase was C18-silica and the 2:3 mixture of methanol and water was used as the eluent at a detection wavelength of 254 nm. The k' values for theobromine, theophylline and caffeine are 0,25, 0,62 and 1,12, respectively. This system enables the detection of 0,2% of theobromine and 0,1% of theophylline in caffeine and 0,2% of caffeine in theobromine or theophylline. In the normal phase system silica was used as the stationary phase while the eluent was 85:15:0,05 mixture of chloroform, dioxane and formic acid. The wavelength of the detection was 273 nm. The k' values of caffeine, theobromine and theophylline are 1,5 4,0 and 5,6, respectively. This system also enables the detection of 0,1% of theophylline and theobromine in caffeine or 0,2% of caffeine in the former. Theophyline and theobromine can be detected in each other at the 0,1% level. PMID- 1872189 TI - Increasing the solubility characteristics of albendazole with dimethyl-beta cyclodextrin. AB - Albendazole is a veterinary anthelminthic drug with excellent effect. Since it is only slightly soluble in water, it is processed in a suspension dosage form as a drench. The solubility and bioavailability of the pharmacon were successfully increased with cyclodextrin derivatives. PMID- 1872190 TI - [Use of isolated myocytes and the patch clamp technic in pharmacological studies]. AB - Effects of palmitylcarnitine, a toxic metabolite of ischaemia, on the electrophysiological properties of single ventricular myocytes of guinea pig were studied by means of patch clamp technique. Cells were enzymatically isolated by perfusing the heart with Ca-free Tyrode solution containing collagenase enzyme. Before experimentation, cells were allowed to recover in a regenerating solution for at least one hour at room temperature. An aliquot of the cell suspension was placed in a small (0.5 ml volume) chamber mounted on the stage of an inverted microscope. After a settling period of 10 minutes, the cells were superfused with Tyrode solution at a rate of 2 to 4 ml/min. Bath temperature was maintained at 35 degrees C. Patch electrodes were fabricated from glass capillary tubes. The electrodes having resistances of 2 to 4 M were connected to a LIST EPC-7 voltage clamp amplifier. The passive parameters (membrane resistance, time constant, capacitance), and resting and action potentials of the cells were recorded in current clamp mode, while the ionic currents (inward calcium, outward potassium) were recorded in voltage clamp mode. Palmitylcarnitine at 10(-6) M concentration increased the membrane resistance, time constant, and depolarized the cell membrane which was accompanied by a marked prolongation of the action potential duration. Under the effect of the drug, the outward potassium current responsible for the repolarization was decreased, while the inward calcium current responsible for the plateau phase was significantly increased mainly at positive membrane potentials. The steady-state activation and inactivation curves were shifted to less negative potentials. The results indicate that the changes in the membrane electrical properties play an important role in the development of the well-known arrhythmogenic effect of palmitylcarnitine. PMID- 1872191 TI - [Experiences with isolated organ studies on pathological human arteries]. AB - Pathological, muscular arteries (common and superficial femoral [FC, FS], anterior and posterior tibial [TA, TP] arteries) of patients suffering from arteriosclerosis obliterans (ASO), thromboangiitis obliterans (TAO), and diabetes mellitus (DIA), removed during amputation of the lower limb were studied as isolated organs. The vessels were cut into transverse rings and contractile force was measured isometrically. The total number of used rings was 828. The following agonists were applied: KCl (80 mM), serotonin (5-HT) (10 microM), prostaglandin F2 alpha (PGF2 alpha) (0.1 mM) or phenylephrine (PE) (10 microM). It was established that applying KCl, 5-HT or PGF2 alpha, the majority of arterial rings display a contraction, but most of the preparations (66%) give no response against PE. The measure of contraction depends on the diagnosis (TAO greater than ASO greater than DIA), on the age of patient and also the anatomical location of the artery in the case of TAO (TP greater than greater than TA), on the associated hypertension in the case of ASO (normotensive greater than hypertensive) and finally on the time elapsed between the operation and usage of preparation if the agonist is KCl. As a conclusion, despite the terminal clinical stage the majority of studied human arteries retained at least a part of their functional integrity. PMID- 1872192 TI - [New results of the clinicopharmacological study on Enzaprost-F (PGF2 alpha) cervical tablets (CHINOIN)]. PMID- 1872193 TI - Histopathologic changes in the cornual portion of the fallopian tube following a single transcervical insertion of quinacrine hydrochloride pellets. AB - To study the sequence of histopathologic changes taking place in the cornual portion of the fallopian tube subsequent to exposure to quinacrine, 252 mg were inserted transcervically in 12 women awaiting hysterectomy for non-malignant conditions of the uterus. All patients who underwent surgery within ten days of insertion were found to have necrosis of the epithelial lining and an acute inflammatory reaction. Later on, the changes observed included progressive absorption of the inflammatory cellular exudate, progressive fibrosis, with partial or almost complete occlusion of the lumen, and failure of regeneration of the epithelial lining. Our results support other studies indicating that quinacrine can effectively produce tubal fibrosis and occlusion. PMID- 1872194 TI - Antiovulatory action of anordrin in the cynomolgus monkey (Macaca fascicularis). AB - Anordrin (2 alpha, 17 alpha-diethynyl-A-nor-5 alpha-androstane-2 beta, 17 beta diol dipropionate) was studied for its antiovulatory potency in the cynomolgus monkey. Anordrin, administered daily on days 9-13 of the menstrual cycle in doses of 4.0 and 8.0 mg/kg body weight, did not inhibit luteal activity in the cycle in which it was given, but delayed the development of ovarian follicles for 5 to 6 months. When a single low dose (0.1 or 0.2 mg/kg b.w.) was administered during the first 3 days of the menstrual cycle, follicular maturation was delayed such that luteal activity was not observed for an average of 26 and 39 days, respectively, and pregnanediol in the ensuing luteal phases was significantly decreased. Anordrin appears to inhibit follicular development when given during the stage of follicular recruitment. PMID- 1872195 TI - Ferritin, a faithful reflection of iron deficiency in IUD wearers with mild vaginal spotting. AB - In a group of 34 parous women, mean age 36.2 years, fitted with a copper releasing IUD (18 with Multiload 250 or 375, and 16 with Nova T) the following parameters were assessed before and 4 months after the device insertion: hemoglobin, hematocrit, iron and ferritin. The only complaint of all patients was the shortening of the menstrual cycle, from 28 +/- 1.2 to 26.8 +/- 1.9 days, and the longer period of days with vaginal spotting (from 3.9 +/- 1.1 to 7.1 +2- 1.0 days). While Hb, HTC and iron remained within normal limits, there was a drastic fall in ferritin, from 24.2 +/- 16.4 to 9.3 +/- 8.7 ng/ml (p less than 0.01), a sign of iron deficiency anemia. Periodic ferritin assessment and iron treatment, if needed, should be the first choice. Removal of the IUD is recommended only when ferritin remains low after antifibrinolytic, prostaglandin synthetase inhibitors, and iron therapy. PMID- 1872196 TI - Prevention of IUD-related pelvic infection: the efficacy of prophylactic doxycycline at IUD insertion. AB - It is believed that much of the small increased risk for developing pelvic inflammatory disease (PID) associated with the use of an intrauterine device (IUD) appears to be caused by bacterial contamination of the endometrial cavity at the time of insertion. Previous research suggests that use of prophylactic antibiotics immediately prior to IUD insertion may reduce the risk of developing PID. This paper presents results from a randomized clinical trial of 1485 women in Ibadan, Nigeria evaluating the effectiveness of 200 mg of doxycycline (versus placebo) given orally at the time of IUD insertion in reducing the incidence of PID during the first three months of IUD use. Rate of PID infection in the doxycycline-treated group was not significantly lower than that in the placebo treated group. The rate of unscheduled IUD-related visits to the clinic also was not significantly lower among the doxycycline-treated group. However, the incidence of PID was low (21 cases) for both study groups. Aseptic conditions during IUD insertion, follow-up visits with short intervals to monitor health, and treatment of opportunistic infections may have reduced the potential of PID within this population. PMID- 1872197 TI - Effects of chlorhexidine-coated intrauterine device on the bacteriology of the uterine cavity. AB - Twenty-nine women, aged 31-53 years, scheduled for an abdominal hysterectomy, participated in this study. The patients were divided into three groups. The first received a Multiload MLCu250 intrauterine device (IUD); the second group received a chlorhexidine acetate medicated Multiload MLCu250 IUD; the third group acted as a control group receiving no IUD. Bacteriological cultures of the vagina and ectocervix were taken prior to insertion of the IUD. At hysterectomy, some 18 hours later, specimens were taken from the cervical canal, uterine cavity, and the device itself, for culture of anaerobic and aerobic organisms using a standardized previously validated technique. In three of the nine control patients, organisms were cultured from the uterine cavity. There were no differences between the bacteriological results of the two groups with medicated and non-medicated devices, with regard to the cultures from the cervical canal, uterine cavity or the devices themselves. Nor was there any difference between the control and the IUD group. PMID- 1872198 TI - [Diabetic retinopathy]. PMID- 1872199 TI - [Age-related changes in the rat lens: morphological and morphometrical studies]. AB - Age-related changes in the lenses of 90 Wistar male rats, whose ages ranged from 7 to 26 months, were studied morphologically and morphometrically. Morphological studies were performed using biomicroscopy, light microscopy, scanning electron microscopy and transmission electron microscopy. Early cataract formation was observed biomicroscopically in rats of 19 months of age and the number of cataractous lenses increased with aging. Age-related morphological changes in the lenses were observed before cataract formation and these histological changes showed various forms with aging. Flat preparations of the lens epithelium were examined with a computer-assisted cell-analyzer. The mean cell density decreased and the mean cell area enlarged in both central and germinative zones of the lens epithelium with aging. These results suggest that age-related changes of lens epithelial cells do occur and may be associated with the formation of Wistar rat cataract. PMID- 1872200 TI - [Changes in cell kinetics of rat lens epithelial cells with aging]. AB - Whole-mount preparations of developing rat lens epithelium were made and 3H thymidine autoradiography was performed on them. The distribution of 3H-thymidine labeled (DNA-synthesizing) epithelial cells was examined by the above combined methods. Labeled cells were evenly distributed in the epithelial cell layer (not the definitely germinal zone) until 1 week after birth. In 3- or 7-week-old rat lens, labeled cells were mainly distributed in the germinal zone, and the number of labeled cells localized in the anterior subcapsular epithelial cell layer decreased according to age of the rat. The 24-week-old rat showed localization of labeled cells at the germinal zone, which seemed to be similar to the human adult lens. PMID- 1872201 TI - [Study on choroidal blood flow at dark and light adaptation. II. Choroidal blood flow at light adaptation]. AB - The effect of light adaptation on choroidal blood flow (CBF) was studied in albino rabbits. CBF was measured by the hydrogen clearance method. There was no significant change of CBF at light adaptation, in which CBF had been expected to decrease due to decreased oxygen demand of the outer retina. The results showed that light adaptation did not influence CBF, in spite of the close relationship between the outer retina and choroidal circulation. Because of the rich blood flow, the choroidal circulation may not need a reaction mechanism for functional changes of the outer retina. PMID- 1872202 TI - [Localization of motoneurons of the vertical yoke muscles in a brainstem of the cat--a double labeling study]. AB - Motor neurons innervating the vertical yoke muscles in cats were investigated using fluorescent dyes by the double labeling method. In 4 cats, the right superior rectus muscle (SR) and left inferior oblique muscle (IO) were injected with 3% fast blue (FB) and 5% diamidino yellow dihydrochloride (DY), respectively, for observing motoneurons innervating yoke muscles involving upward gaze. In 4 other cats, the left inferior rectus muscle (IR) and right superior oblique muscle (SO) were injected with 3% FB and 5% DY, respectively, to observe motoneurons innervating yoke muscles involving downward gaze. After SR and SO injections labeled cells were found in the bilateral oculomotor nucleus and the bilateral trochlear nucleus, respectively, predominantly on the contralateral side. Following IR and IO injections labeled cells were found only in the ipsilateral oculomotor nucleus. No double labeled cell was observed in any labeled neurons, which indicates that each of the yoke muscles was innervated by independent individual motoneurons. According to the present observation and past reports on rats, cats and monkeys, motoneurons innervating SR and SO have developed from lower mammals such as the rat into predominantly contralateral innervation in the monkey, from a phylogenetic point of view. On the other hand, compared to contralateral innervation in lower mammals, motoneurons innervating IR and IO have developed into ipsilateral innervation in the monkey. PMID- 1872203 TI - [A double-labeling study of serotonin neurons that project to the visual cortex of developing rat brain]. AB - Immunohistochemical studies of developing rat brains revealed aggregation of serotonin terminal fibers in the visual cortex at from 7 to 14 postnatal days. This aggregation is transient, disappearing 2 weeks after birth. The cells of origin of these serotonin terminals were investigated using double-labeling with retrogradely transported WGA-apoHRP-Au and serotonin immunohistochemistry. WGA apoHRP-Au was injected into the rat visual cortex on the 9th day after birth. The rats were allowed to survive for 2 days and sacrificed with perfusion. Cryostat sections of the brain were processed with silver-enhancement to develop the retrogradely transported WGA-apoHRP-Au, and then serotonin immunohistochemistry was performed. Double-labeled cells that were labeled with WGA-apoHRP-Au and serotonin-immunoreactive were found mostly in the raphe medianus and raphe dorsalis in rostral and caudal sections of the mesencephalon, respectively. PMID- 1872204 TI - [Effect of the start of glycemic control on the progression of diabetic retinopathy]. AB - The effect of the start of glycemic control on retinopathy progression was investigated. The changes of glycosylated hemoglobin (HbA1) were compared between the retinopathy progression group (Group 1, 24 eyes) and the non-progression group (Group 2, 23 eyes). The follow-up period was 24 months. The grades of retinopathy, age, duration of diabetes mellitus (DM), sex, and manner of DM control in these subjects were matched between the two groups. They were classified into 9 strata according to the matched systemic factors. In Group 1, HbA1 value decreased rapidly 6 or 7 months before the retinopathy progression, but did not change in Group 2 during 24 months. The change rate was significantly different between Group 1 and Group 2. The block efficacy for 6-7 months follow up was also statistically significant between the two groups by analysis of variance (ANDVA). The estimated mean HbA1 value for the 9-10 month period in Group 1 was 2.46% less than that of Group 2. The higher the HbA1 value, the higher the relative risk (odds ratio) of retinopathy progression. The relative risk of retinopathy progression of the mean HbA1 value was highest for 9-10 month period. The relative risks of 1, 2, and 3% decrease of HbA1 for 9-10 months were 1.7, 2.8, and 4.7, respectively. PMID- 1872205 TI - [A follow-up study of pupillary dynamics in patients with ocular hypertension and primary open angle glaucoma]. AB - The authors previously reported light reflex abnormalities and adrenergic supersensitivity to topical epinephrine (DPE; dipivalyl epinephrine) of the pupils in patients with ocular hypertension (OH) and those with primary open angle glaucoma (POAG). In this investigation, we attempted to reconfirm pupillary light reflex abnormalities we reported previously, and to investigate the relationship between the normotensive effect of 0.1% DPE and the pupillary light reflex abnormalities in OHs and POAGs. A total of 11 OHs and 11 POAGs under good oculotensive control with neither mydriatics nor miotics were examined. They were measured by an open-loop photically stimulated infrared videopupilogram, and were neurologically diagnosed by comparing the simulated patterns of the light reflex made by topical autonomic agents. When we considered the progress of the stage of POAG, both OHs and POAGs showed satisfactory reproducibility of pupillary light reflex abnormalities. Other cases in which light reflexes altered, showed worsening of the visual field deficit, which was prominent when OHs developed into POAG. OHs with significant reduction of intraocular pressure (IOP) after topical administration of 0.1% DPE showed various kinds of abnormal pupillary light reflexes. On the contrary, cases with little reduction of IOP after 0.1% DPE instillation showed normal pupillary light reflexes in OHs and afferent pupillary defect on POAGs. PMID- 1872206 TI - [An epidemiological study on the prevalence of the narrow chamber angle in Japanese]. AB - Primary angle-closure glaucoma (PACG) has been reported to be more prevalent in Orientals than in Caucasians. However, our knowledge about the epidemiology of narrow angle and PACG in Orientals is still extremely limited. To determine the prevalence of narrow angle and PACG in Japanese, we carried out gonioscopic and oculometric examinations as a part of the first nationwide, multicenter glaucoma survey in Japan. We also estimated the angle width by means of van Herick's method to assess the efficacy of this method in detecting narrow angle. Of 1,979 inhabitants 40 years or older of a town in Gifu Prefecture, 585 (29.6%) participated in the study and underwent tonometric, gonioscopic and oculometric examinations. The width of the angle was estimated by van Herick's method prior to gonioscopy. Of the group tested, the prevalence of grade 0 to 2 angles (Shaffer's classification) was found in 8.0%, which was significantly more frequent than among Caucasians. The prevalence of grade 1 or narrower angle and PACG was 2.6% and 0.3%, respectively, neither of which was significantly different from rates reported among Caucasians. Using the gonioscopic determination as a gold standard, van Herick's method was noted to have a sensitivity of 77% and a specificity of 94% in identifying eyes with the angle of grade 2 or narrower, while both the sensitivity and specificity of this method were above 90% in detecting an angle of grade 1 or narrower. It was concluded that van Herick's method was useful in detecting the extremely narrow angle. PMID- 1872207 TI - [Advancement of the anterior portion of the superior oblique tendon in case of traumatic bilateral trochlear palsy]. AB - The effect of the advancement of the anterior portion of the superior oblique tendon on cyclovertical and horizontal deviation was studied in seven cases of traumatic bilateral trochlear palsy by using a synoptometer (Cuppers) and cyclodevinometer (Kolling). The anterior portion of the superior oblique tendon was disinserted and advanced laterally according to the amount of the cyclodeviation in primary position with 1 degree/mm. Surgery was done in 5 cases on both eyes, in 2 cases on one eye. The age of the patients ranged from 20 to 64 years (mean 45 years). The excyclodeviation was significantly reduced (p less than .01), however overcorrection was found in the upward gaze. The mean reduction of excyclodeviation in diagnostic positions of gaze was approximately 10-12 degrees. The vertical deviation was significantly reduced in up and downward gaze (p less than .05), nevertheless overcorrection was found in the upward gaze. The mean reduction of the vertical deviation differed according to their positions of gaze. V-pattern esotropia could not be reduced significantly. Therefore an alternative operative approach must be found which can avoid overcorrection in the upward gaze and moreover correct V-pattern esotropia in the downward gaze. PMID- 1872208 TI - [A long-term follow-up of a patient with DIDMOAD (Wolfram) syndrome]. AB - A 19-year-old Japanese woman developed diabetes mellitus, diabetes insipidus and optic atrophy. Other abnormal ocular findings included color blindness, elevated dark adaptation threshold and constriction of visual fields. Diabetic retinopathy, which is considered to be rare in this syndrome, also was found in the fundi of this patient. During the nine-year follow-up period, diabetic retinopathy deteriorated despite treatment by photocoagulation and vitrectomy, suggesting the importance of ophthalmological examinations in patients with DIDMOAD syndrome. PMID- 1872209 TI - [Transport of substances across the retinal pigment epithelium]. PMID- 1872210 TI - [Is vitreous surgery for intraocular proliferative changes a combined surgery or a single surgery?]. PMID- 1872211 TI - [Vitreous surgery for intraocular proliferative disorders]. AB - Before the advent of vitreous surgery, many intraocular proliferative disorders were incurable. The present paper reviews the pathogenesis, classification and vitreous surgery treatment of these diseases. Intraocular proliferative disorders are classified into two categories: vascular and non-vascular, also their indications for vitreous surgery are reviewed. General surgical techniques for intraocular proliferative disorders are discussed, as are specific surgical techniques for "vascular" proliferative diabetic retinopathy and "non-vascular" proliferative vitreoretinopathy, and current assessments of the usefulness of vitreous surgery. Vitreous surgery for intraocular proliferative disorders requires extensive high-technological equipment for the integration of various surgical techniques such as lensectomy, vitrectomy, membrane dissection, intraoperative retinal reattachment, closure of retinal breaks, panretinal endo photocoagulation, scleral buckling, intraocular tamponade and so forth. Vitreous surgery for intraocular proliferative disorders is beneficial only when these procedures are appropriately performed. PMID- 1872212 TI - [Morphology of live retinal pigment epithelial cells]. AB - We attempted to observe, by means of fluorescein angiography, the retinal pigment epithelial cells in pigmented rabbits. Fluorescein angiography was performed in 31 pigmented rabbits, after intravenous injection of 14mg/kg fluorescein sodium. The angiograms were evaluated as prints and as negative film under a light microscope. Animals were sacrificed and submitted to studies by scanning electron microscopy and fluorescein light microscopy. On fluorescein angiograms, we observed mosaic pattern which consisted of numerous polygonal spots overlying choroidal vasculature. Each polygonal spot showed central hypofluorescent area surrounded by hyperfluorescent rim. They were seen in all the eyes except 4 lightly pigmented eyes. They seemed to correspond, in size, to each retinal pigment epithelial cell. This pattern appeared from the early choroidal phase on, to become more distinct 5 to 15 minutes after dye injection. A hexagonal pattern was regularly seen away from the medullary rays by 3 or more disc diameters. The pattern became larger in the periphery than in the posterior pole. These angiographic findings closely matched those of retinal pigment epithelial cells as seen by scanning electron microscopy and fluorescein light microscopy in sizes and shapes. The findings indicate that it is possible to identify retinal pigment epithelial cells in pigmented rabbits by conventional fluorescein angiography. PMID- 1872213 TI - [Kinetic study of movement of fluorescein across the isolated rabbit retinal pigment epithelium--choroid]. AB - Using an Ussing-type chamber, the transport of fluorescein (F) across the isolated retinal pigment epithelium (RPE)-choroid of the rabbit was studied. The outward movement (from the vitreous to the choroidal side) of F was significantly greater than the inward movement (from the choroidal to the vitreous side) and was suppressed by the application of 10(-4)M probenecid, 30mM hippurate or 5mM iodipamide to 41%, 45% or 39% of the control, respectively, while the inward movement was not affected by any of these agents. As the F concentration in the chamber increased, the inward movement of F also increased in a linear fashion, but the outward movement showed nonlinearity. The difference between the outward and inward movement of F was thought to represent the net flux of F across the RPE-Choroid and this value showed nonlinearity and saturation as the F concentration increased. The Lineweaver-Burk plot of the reciprocals of the net flux of F concentration gave the apparent Km of 4.5 x 10(-5)M and apparent Vmax of 2.27 nmoles/hr/cm2, which suggested that the F transport system in the rabbit RPE-Choroid had a greater affinity to the substrate but lower transporting capacity as compared with the F transport system in the rabbit iris-ciliary body or the ascorbate transport system in the iris-ciliary body. PMID- 1872214 TI - [Analysis of transport of fluorescein across the isolated retinal pigment epithelium-choroid using an ussing type chamber]. AB - Retinal pigment epithelium (RPE)-choroid preparations from albino rabbits were sealed in an Ussing type chamber under stabilized conditions for 3 hours. The transepithelial potential was 1.2 +/- 0.08 mV and the transepithelial resistance was 175.2 +/- 9.1 omega.cm2 (mean +/- SE, n = 16). The transport of fluorescein across the isolated rabbit RPE-choroid was studied under short circuit condition and outward (vitreous----choroid) and inward (choroid----vitreous) permeability to fluorescein were determined. The outward permeability was 1.63 +/- 0.20 x 10( 5) cm/sec and inward permeability was 0.44 +/- 0.13 x 10(-5) cm/sec (mean +/- SE, n = 8). The former was 4 times greater than the latter (p less than 0.01). The outward permeability was decreased to 1.02 +/- 0.08 x 10(-5) cm/sec (n = 7), 0.75 +/- 0.11 x 10(-5) cm/sec (n = 5), 0.67 +/- 0.11 x 10(-5) cm/sec (n = 6) by 10(-6) M of ouabain, 10(-5) M of 2,4-dinitrophenol and 10(-4) M of probenecid, respectively. Low temperatures (0.5-1.0 degree C) markedly decreased the outward permeability to 0.05 +/- 0.04 x 10(-5) cm/sec (n = 4, mean +/- SE). These results suggest that active transport plays a role in the outward movement of fluorescein across the rabbit RPE-choroid. PMID- 1872215 TI - [Effects of fixation and light conditions on distribution of interphotoreceptor matrix]. AB - By using albino, adult rats, the effects of different light conditions during enucleation and fixation on the staining of the interphotoreceptor matrix (IPM) with colloidal iron were examined. When the eyes were enucleated in the dark or under a fluorescent lamp, followed by immersion-fixing in the dark, the IPM around the photoreceptor outer segments (OS) and apical inner segments (IS) was uniformly stained. When the eyes were enucleated in the light, and were immersion fixed in the light, the staining pattern of the IPM was dependent on the light conditions during the fixation. By increasing the intensity and the exposure-time of the light, the intensity of the interstitial IPM-staining around the OS decreased except for the apical- and basal-regions, whereas that of the IPM staining around the IS increased from the basal- to the apical-region. When the rat was perfused with the fixative in the light, the diffuse IPM staining around the IS was especially remarkable. In cases in which it is only possible to apply immersion-fixation, it is necessary to remove the light effects during the fixation in order to obtain consistent results with IPM-histochemistry. For this purpose, it may be effective to cover the bottle for fixation with aluminum foil immediately after the enucleation. PMID- 1872216 TI - [Classification of light-evoked distribution of interphotoreceptor matrix]. AB - Distributional patterns of the interphotoreceptor matrix (IPM) under several different light conditions were examined in adult rats using colloidal iron staining. In the dark, the IPM distributed uniformly throughout photoreceptor outer segments including apical halves of inner segments. After exposure to light for 1 min, the colloidal iron-bound IPM concentrated in bands at apical and basal regions of outer segments and at apical inner segments. After exposure to light for 5-30 min, the IPM distributed throughout inner segments, in addition to the distribution at apical and basal outer segments. In excessive light, diffuse IPM staining was observed throughout the photoreceptor layer. These findings suggest that the light response of the IPM around outer segments precedes that around basal inner segments. It is also remarkable that the excessive light-induced distributional pattern of the IPM is similar to patterns in inherited retinal dystrophy and light-induced retinal degenerations. PMID- 1872217 TI - [Retinal tissue damage and lipid peroxidation in experimental autoimmune uveoretinitis]. AB - Retinal lipid peroxidation products were measured at various stages of experimental autoimmune uveoretinitis (EAU) induced in Lewis rats by retinal S antigen. Histopathologic examination and measurement of myeloperoxidase, which is a quantitative marker of polymorphonuclear leukocytes (PMNs) in tissue, were also performed. The results showed that lipid peroxidation is closely implicated in the progression of uveoretinitis, and is related to the cellular infiltrate, which consisted primarily of PMNs, and to the retinal tissue damage. These findings may support the theory that oxygen-free radicals liberated from activated PMNs play a role in retinal tissue damage via peroxidation of membrane lipids. To ascertain the tissue damage caused by the lipid peroxidation products generated in the eye, intravitreal injection of an oxidized docosahexaenoic acid, a major polyunsaturated fatty acid in the photoreceptors of the retina, was performed and its toxicity in the retina was proved histologically. PMID- 1872218 TI - [Mouse corneal degeneration by bovine cornea-specific protein]. AB - In a previous study, IgG deposits and changes were found in the corneal epithelial cells of BALB/c mice immunized by cornea-specific protein (CSP) contained in the bovine cornea. We observed the corneal changes in mice by immunoreaction to CSP for 6 months with slit-lamp microscopy, and found granular opacity under the central corneal epithelium. Histologically this opacity was composed of scattered deposits in the corneal substantia beneath the basal layer of the epithelium. The corneal epithelium in contact with the deposits became atrophied and flattened. The deposits were stained with PAS staining, and with ConA, WGA and RCA by the lectin enzyme histochemical method. Therefore, these results indicate that these deposits possess N-acetyl-D-glucosamine as a sugar residue. In the degenerated corneal epithelium, peroxidase-staining by the anti CSP antibody enzyme histochemical method weakened and ConA-positive cells were obviously decreased. This suggests that the production of CSP decreased in the same lesion and that disorder of sugar metabolism developed at the corneal epithelium. PMID- 1872219 TI - [Gangliosides in human senile cataractous, monkey, and rat lenses]. AB - Our previous studies suggested that increases in certain polysialogangliosides are associated with the maturation of senile cataract and that these gangliosides possess an unknown sugar chain different from those of brain gangliosides. To study these gangliosides, crude ganglioside fractions from human, monkey, and rat lenses were isolated by solvent extraction and DEAE-Sephadex column chromatography, analyzed by thin-layer chromatography, and subjected to ganglioside mapping by high-performance liquid chromatography with DEASE Iatrobeads. The distribution pattern of gangliosides obtained by mapping demonstrated the presence of the polysialogangliosides in monkey and rat lenses. The ganglioside pattern of monkey lens as shown by two-dimensional thin-layer chromatography was similar to that of human senile cataractous lens and was characterized by the presence of unidentified spots. These results indicate that certain polysialogangliosides are unique to lens and are synthesized by an unidentified pathway. PMID- 1872220 TI - [Relation between metabolic and histological changes in the rat lens during the pathogenesis of galactose cataract]. AB - A comparative study of the metabolic kinetics of organophosphate compounds, biochemical changes and histological changes, in the rat lens during the process of the generating galactose cataract. The change of alpha-glycerophosphate (alpha GP) with time was analogous to that of dulcitol and the decrease of alpha-GP depended on histological destruction. Furthermore phosphorylcholine decreased considerably before adenosine triphosphate (ATP) decreased, the latter commencing when the histological destruction of the lens progressed to all around the lens. In addition, inositol decreased rapidly after ingestion of galactose. It was concluded that the decrease of alpha-GP was caused by the flow from the lens, and the decrease of ATP started from the epithelium in the lens. Therefore, it was speculated that the decrease of inositol was caused by decrease in the active transport of inositol. PMID- 1872221 TI - [The effect of trabeculotomy on the day-time variation of intraocular pressure of the primary open-angle glaucoma]. AB - We selected 34 eyes with primary open-angle glaucoma cases having glaucomatous visual field loss, but with relatively low base-line intraocular pressure (average intraocular pressure at normal office hour, below 20mmHg) and with one or more episodes of intraocular pressure over 21mmHg in a diurnal fluctuation estimated at 8:30, 9:30, 11:30, 13:30, 15:00 and 17:00. They were treated with trabeculotomy ab externo and we compared the pre- and postoperative diurnal fluctuation pattern of the intraocular pressure. The mean of the base-line intraocular pressure decreased from 18.4 to 16.3mmHg. The mean values of the maximal pressure of the diurnal estimation and of the diurnal difference (maximum minus minimum) also decreased, from 23.4 to 17.9 and from 7.4 to 3.9mmHg, respectively. In 31 eyes (91%) the individual maximal value did not exceed 20mmHg postoperatively. From these findings, it was speculated that trabeculotomy can be effective on primary open-angle glaucoma with relatively low intraocular pressure. PMID- 1872222 TI - [On factors related to the width of anterior chamber angle--multivariate analysis of biometrically determined values]. AB - Primary angle-closure glaucoma (PACG) is associated with certain biometric ocular features such as shallow anterior chamber, axial hyperopia, increased thickness of the lens and small corneal diameter. The vast majority of previous studies on PAGG has shown that females are affected more frequently than males. In an attempt to study the relationship between the angle width and ocular dimensions, we carried out gonioscopic examination and biometric measurements (corneal diameter, corneal radius, anterior chamber depth, lens thickness, relative lens position and axial length) in 1,169 eyes of 585 adult subjects who participated in the glaucoma screening in Gifu Prefecture. It was found that the angle width significantly correlated with each biometric value. The coefficient of determination calculated by multiple regression analysis was 0.41, suggesting that factors other than these are involved in determining the angle width. When the angle width of females was compared to that of males with identical refractive errors and biometric values, the angle width of females was significantly narrower than that of males. Hence, the difference in ocular dimensions does not adequately explain the higher incidence of narrow angle in females. Increased asymmetry of angle width between a pair of eyes with aging appeared to be related to asymmetry of lens thickness, anterior chamber depth and lens position. PMID- 1872223 TI - [Diurnal variation of intraocular pressure in low tension glaucoma]. AB - Around-the clock intraocular pressure (IOP) measurement were performed in 104 eyes of 52 low tension glaucoma (LTG) cases. Subjects were all hospitalized and IOP measurements were done every 2 hours from 6:00 AM to 12:00 PM and every 3 hours from 12:00 PM to 6:00 AM. All LTG patients met the following criteria, (1) glaucomatous optic nerve head change and corresponding visual field defect, (2) normal open angle, (3) IOP less than or equal to 21mmHg at any time of IOP measurement, (4) no obvious neurological or rhinological disorders that could affect the optic nerve, (5) no history of hemodynamic crisis or cardiovascular disorders except mild hypertension. Peak IOPs were most frequently observed at 10:00 AM, but about 55% of all observed peaks were in the time period from 6:00 PM to 8:00 AM. Most troughs were observed from 2:00 PM to 10:00 PM. The mean IOP, the diurnal variation and the difference between both eyes in the same person averaged 14.1, 4.9, and 0.6mmHg, respectively. Assuming that the period of rhythm is 24 hours, the results of IOP measurements fitted a cosine curve using the least square method. In 44% of all eyes, significant correlation coefficient (r greater than or equal to 0.6, p less than 0.05) between the measured and the predicted IOPs was noted, and an equation, IOP = 14.3 + 1.7cos 2 pi (t/24-0.4 radian), was obtained. Comparing the present results with former ones, we concluded that the IOP changes in LTG patients were similar to those in normal individuals. PMID- 1872224 TI - [Two cases of posterior keratoconus]. AB - We studied 3 eyes from 2 patients with posterior keratoconus. One patient (a 17 year-old female) had posterior keratoconus bilaterally and the other (a 8-year old male) had posterior keratoconus in one eye and Peters' anomaly in the contralateral eye. Slit-lamp biomicroscopy disclosed localized thinning with stromal haze underlying the endothelium in the central cornea. Photokeratoscopy revealed no abnormalities suggestive of anterior keratoconus. Wide-field specular microscopy showed the endothelial cells with normal cell density (approximately 3500 cells/mm2) and morphology in both the peripheral and central corneas (adjacent to the hazy areas). PMID- 1872225 TI - Imaging of vascular complications associated with renal transplants. AB - Vascular complications associated with renal transplants are a significant cause of graft dysfunction. The most common complications are arterial and venous stenoses and thromboses and intrarenal and extrarenal arteriovenous fistulas and pseudoaneurysms. Although angiography is the imaging gold standard for the diagnosis of these disorders, Doppler sonography, scintigraphy, and occasionally CT are capable of detecting them. An awareness of the different imaging appearances of each complication will aid in their early detection and treatment. In this review, we present this information and provide a perspective on the relative roles of these techniques in the detection of vascular complications from renal transplants. PMID- 1872226 TI - Diffuse pulmonary alveolar hemorrhage after bone marrow transplantation: radiographic findings in 39 patients. AB - Diffuse alveolar hemorrhage is a life-threatening complication after bone marrow transplantation. We investigated the radiographic abnormalities that occurred in 39 transplantation patients with a diagnosis of diffuse alveolar hemorrhage and correlated the findings with the patients' clinical course. The initial radiographic abnormalities after diffuse alveolar hemorrhage developed an average of 11 days after bone marrow transplantation, and the radiographic abnormalities preceded the clinical diagnosis by an average of 3 days. Twenty-seven patients initially had bilateral radiographic abnormalities; 10 initially had unilateral abnormalities (seven in the right lung, three in the left lung). Two patients had normal chest radiographs throughout their clinical course. All 37 patients with radiographic abnormalities had abnormalities involving the central portion of the lung, primarily the middle and lower lung zones. The initial radiographic pattern was interstitial in 27 and alveolar in 10. In 24 patients, radiographic abnormalities were initially judged to be mild; three were severe from the onset. Radiographic abnormalities rapidly worsened in most patients over 6 days. In 30 patients, diffuse bilateral radiographic abnormalities involving all lung zones developed. Eleven patients persisted in having only interstitial radiographic abnormalities; 26 had a confluent alveolar pattern. At the height of radiographic abnormalities, 27 cases were judged to be severe, and only one case was judged to be mild. The mortality rate in patients with diffuse alveolar hemorrhage was 77%. The radiographic abnormalities of diffuse alveolar hemorrhage are nonspecific and usually precede the clinical diagnosis. The clinical course after hemorrhage is short, often resulting in death. PMID- 1872227 TI - Motion artifact simulating aortic dissection on CT. AB - We recently imaged two patients clinically suspected of having aortic dissection whose contrast-enhanced CT examinations, obtained on a new scanner with a 1-sec scanning time, showed findings suggesting an ascending aortic dissection. The subsequent clinical course and evaluation implied that the CT findings were predominantly artifactual. We identified identical artifacts in 18% of 50 consecutive contrast-enhanced CT examinations performed for a variety of indications on the same scanner. The double-lumen artifact, simulating an intimal flap, occurs in the proximal ascending aorta and is limited to one or two contiguous transaxial images. The artifact was not detected on two other CT units. We believe the artifact arises from motion of the aortic wall and the surrounding pericardial recesses during image acquisition. PMID- 1872228 TI - Mediastinal thymolipoma. PMID- 1872229 TI - Current status of mediastinal sonography in the posttreatment evaluation of patients with lymphoma. PMID- 1872230 TI - Torsion of the upper lobe of the lung after surgery: findings on pulmonary angiography. PMID- 1872231 TI - The American College of Radiology Mammography Accreditation Program. AB - This article discusses the background, goals, criteria, current results, impact, and future directions of the American College of Radiology's (ACR's) Mammography Accreditation Program. To date, approximately one half of the mammographic units in the United States have voluntarily applied for accreditation through the ACR program, with approximately one quarter of the units in the United States now accredited. Application rates have increased steadily since the start of the program in August 1987. The equipment performance criteria and professional criteria defined and employed in the ACR Mammography Accreditation Program have been adopted as standards for the performance of screening mammography by the ACR and have served as a basis for quality assurance standards in state and federal legislation on mammography. PMID- 1872232 TI - Self-referred mammography patients: analysis of patients' characteristics. AB - Among mammography patients, a small but growing group of highly motivated women refer themselves directly for screening without the suggestion of their physicians. We surveyed 485 patients during a 3-month period to study how self referred mammography patients differ from physician-referred patients. Self referred patients were more likely than physician-referred patients to have a family income of more than $30,000 per year, to be college graduates, and to consider their health as good or excellent. A large percentage of self-referred patients performed other health-promoting practices, but were not significantly more likely to do these than were physician-referred patients. Women who referred themselves were more likely to have a friend with breast cancer and to believe that cancer could be cured. They expressed much less worry about radiation exposure and were more likely to consider $50.00 an appropriate charge for a screening mammogram. By far, the greatest motivator for self-referred patients was health promotion and disease prevention. Self-referred mammography patients tend to be wealthier, more education, and less concerned about the cost and radiation dose of mammography when compared with physician-referred mammography patients. PMID- 1872233 TI - Altered gallbladder contractility after extracorporeal shock-wave cholecystolithotripsy. AB - Change in gallbladder contractility after biliary extracorporeal shock-wave lithotripsy (ESWL) may significantly influence the clearance of fragments after successful gallstone fragmentation. We assessed changes in gallbladder contractility in response to an oral fatty meal in 50 patients 1 month after biliary ESWL (all fragments were smaller than 3 mm) and also in a separate group of 10 patients 3 months after complete clearance of fragments. The prevalence of persistent lumen-obliterating contraction of the gallbladder after biliary ESWL also was analyzed in 325 patients. Gallbladder contractility remained unchanged in 30, increased in nine, and decreased in 11 of the 50 patients. The average reduction in the fasting gallbladder volume after lithotripsy was 28% (p less than .001). Gallbladder contractility remained unchanged 3 months after complete clearance of fragments in six of 10 patients studied separately. A decrease (n = 2) or increase (n = 2) in contractility was seen in the remaining patients. No significant difference occurred in the average ejection fraction of the gallbladder before lithotripsy and after complete clearance of the fragments. Thirty-four of the 325 patients who have so far undergone biliary ESWL had a completely contracted gallbladder with no lumen visible on sonography. The gallbladder returned to a relaxed state in half of these patients within 1-9 months. Thus, biliary ESWL did not significantly alter gallbladder contractility in 60% of patients. A significant reduction in the volume of the fasting gallbladder occurred after lithotripsy. Successful clearance of fragments did not improve the contractility of stonebearing gallbladders in the majority of patients. PMID- 1872234 TI - Placement of a metallic biliary endoprosthesis via cholecystostomy. PMID- 1872235 TI - MR demonstration of edema adjacent to a liver metastasis: pathologic correlation. PMID- 1872236 TI - Endorectal sonography in the evaluation of rectal and perirectal disease. AB - Endorectal sonography initially was developed for evaluation of the prostate and now has been adapted for evaluation of rectal and perirectal disease. We used endorectal sonography to evaluate a spectrum of diseases, including primary and recurrent rectal carcinoma, metastases, villous adenoma, leiomyosarcoma, endometriosis, sacrococcygeal teratoma, chordoma, retroperitoneal cystic hamartoma, pelvic lipomatosis, diverticulitis, and perirectal abscess. The technique has been useful in localization of perirectal abscesses and in sonographically guided biopsy of perirectal masses. Knowledge of normal sonographic anatomy of the rectum is essential in the evaluation of rectal and perirectal disease. In this essay, we describe the technique of endorectal sonography and illustrate the sonographic findings in a variety of diseases. PMID- 1872237 TI - Bilateral testicular infarction caused by epididymitis. PMID- 1872238 TI - Insertion of the Simon nitinol caval filter: value of the antecubital vein approach. PMID- 1872239 TI - Cervical paraspinal calcification in collagen vascular diseases. AB - Although soft-tissue calcification is common in collagen vascular disease, paraspinal calcification in the cervical spine has not been described before. We studied five women with large, lobulated, predominantly homogeneous calcific masses centered on synovial articulations in the neck. Changes consisting of either osteolysis or erosions were evident. All patients had radiculopathy, focal pain, or stiffness. In two patients, the presence of hydroxyapatite crystals was confirmed on biopsy. Symptomatic cervical paraspinal calcifications in patients with collagen vascular disease cause large soft-tissue masses that mimic tumoral calcinosis. PMID- 1872240 TI - Diagnosis of osteomyelitis of the foot in diabetic patients: value of 111In leukocyte scintigraphy. AB - The noninvasive diagnosis of osteomyelitis of the foot in diabetic patients with currently available radiologic and radionuclide imaging techniques is often difficult. Recently, 111In-labeled leukocyte scintigraphy has been proposed as an attractive alternative. Accordingly, we retrospectively reviewed 51 111In-labeled leukocyte scans, 49 technetium-99m bone scans, and 49 plain radiographs obtained in 51 adults with diabetes in whom osteomyelitis of the foot was suspected. The sensitivity and specificity of these techniques were evaluated in all patients, as well as in a subgroup of 11 patients with neuroarthropathy. Results with 111In labeled leukocyte scans were also examined in subsets of patients with soft tissue ulcers (n = 35) and those receiving antibiotics during investigation (n = 20). Confirmation or exclusion of osteomyelitis was made surgically in 28 patients and clinically in 23. Fourteen patients had osteomyelitis. Bone scans were most sensitive (93%) but least specific (43%); plain radiographs were most specific (83%) but least sensitive (43%). 111In-labeled leukocyte scans were both sensitive (79%) and specific (78%), and remained useful in patients with neuroarthropathy, soft-tissue ulcers, and antibiotic treatment. Poor spatial resolution contributed to the false-negative and false-positive 111In-labeled leukocyte scans, suggesting that this technique should not be interpreted independent of other tests. 111In-labeled leukocyte scans are a valuable diagnostic tool for the diagnosis of pedal osteomyelitis in diabetic patients. PMID- 1872241 TI - Photostimulable phosphor digital radiography of the extremities: diagnostic accuracy compared with conventional radiography. AB - A direct comparison was made between digital and conventional radiographs to assess the relative accuracy of a photostimulable phosphor digital imaging system in detecting and localizing minor trauma in the extremities. Matched sets of images were obtained on 103 patients who came to the emergency department for radiographs of the hand, wrist, foot, or ankle. One set was obtained with a conventional screen/film system. The other set was obtained with photostimulable phosphor digital cassettes. The two sets of images of each patient were independently interpreted by three radiologists in a blinded fashion. The findings of each of these three readers were compared with the consensus opinion of two different radiologists. Receiver-operating-characteristic (ROC) curves were plotted for each of the three readers, areas under the curves were calculated, and true-positive fractions were determined at false-positive fractions of 0.1. Although no significant differences in the areas under the ROC curves for the two imaging systems were detected, conventional radiography showed a slight advantage. However, when true-positive fractions for fracture detection were compared at false-positive fractions of 0.1 a statistically significant difference was shown, with conventional screen/film radiography being more sensitive. This study raises questions about the use of currently available photostimulable phosphor systems for imaging trauma of the extremities and suggests that those systems should not be used exclusively. PMID- 1872242 TI - Normal length of fetal kidneys: sonographic study in 397 obstetric patients. AB - This study was done to measure normal lengths of fetal kidneys sonographically during pregnancy. Knowledge of these measurements may allow earlier diagnosis of a variety of abnormalities. The greatest length of each of 498 kidneys in 397 consecutive fetuses between 18 and 41 weeks gestation was measured on sonograms. Gestational ages were determined by last menstrual period and biometry; significant discrepancies led to case exclusion. Abnormal fetuses, twins, offspring of diabetic mothers, and fetuses with renal pelvic dilatation of 4 mm or greater were excluded to avoid any questionable measurements. The results show that mean lengths are greater and confidence intervals are wider than previously reported. Renal lengths are similar to those reported in premature and full-term neonates. Strong correlation exists between renal length and gestational age, determined by biparietal diameter, femoral length, and abdominal circumference, and an average of the three. No significant difference was found between right and left renal lengths in fetuses in whom both kidneys were imaged. Average renal lengths are significantly different when compared across the range of gestational ages (p less than .001). No correlation is seen (r = .00) between parental height or weight and fetal renal length. Our results show that fetal renal lengths are longer than previously reported. PMID- 1872243 TI - Benign hemorrhagic adrenocortical macrocysts in Beckwith-Wiedemann syndrome. AB - A new pseudotumorous lesion found in the adrenal cortex of six infants with Beckwith-Wiedemann syndrome is described. These cystic masses were discovered either prenatally by using sonography or early in the neonatal period as palpable flank masses. Imaging studies, including sonography and CT, could not confidently exclude malignancy. After the masses were removed surgically, histologic examination showed them all to be benign hemorrhagic macrocysts within the capsule or permanent cortex (in contrast to neonatal adrenal hemorrhage, which usually occurs more centrally in the fetal cortex). The cysts were as large as 8 cm in diameter, and in one case a solitary cyst was predominant. Hemihypertrophy was present in all cases. Four of the six lesions were right-sided, and there was a male-female ratio of 5:1. Benign hemorrhagic adrenocortical macrocysts are a cause of abdominal mass in the fetus and neonate with Beckwith-Wiedemann syndrome. PMID- 1872244 TI - Goitrous cretinism manifesting as newborn stridor: CT evaluation. PMID- 1872245 TI - Biological classification of soft-tissue vascular anomalies: MR correlation. PMID- 1872246 TI - Analysis of economics and use of MR imaging units in the United States in 1990. AB - Personnel from the 72 facilities with the most experience in MR imaging were surveyed, and 45 questionnaires were returned with data to study the economics and use of MR imaging facilities. The data from 1990 were compared with results of studies done in 1985 and 1987. The facilities studied were highly selected, and the data and conclusions are unlikely to be representative of all MR facilities currently operational in the United States. The "typical" MR unit operated about 66 hr per week and imaged 68 patients. Most procedures were examinations of the head and spine (73%), with examinations of bone and joint increasing in frequency (17%). Scheduling delays for both inpatients and outpatients have decreased since 1987, indicating that clinical demand is being met by MR facilities. The global (technical plus professional) charge for an examination was approximately $950, and the charge for IV contrast material was an additional $200. IV contrast material was used in approximately 40% of head and 20% of spine studies. The typical MR units in 1990 was used to examine more than 3000 patients per year at a charge of approximately $750 each for the technical component. Technical billings for each unit were approximately $2.3 million, and net revenues were almost $1.9 million. We estimate the annual operating cost of an MR unit in 1990 was $1.3 million, so the typical MR unit had an annual net profit of approximately $500,000. This is a considerable improvement from the economic position in 1985, when each MR unit was losing approximately $400,000 annually. We conclude that experienced MR imaging facilities are now profitable owing to increased efficiency and continually rising charges. We suggest the economic historical pattern demonstrated by MR imaging (large losses initially followed by profitability within several years owing to increased efficiency and higher charges) is a typical pattern for many new technologies with the current medical payment system in the United States. PMID- 1872247 TI - The volume and cost of radiologic services in the United States in 1990. AB - Knowing the total number of radiologic services provided in the United States and their cost is important. This information can, for example, indicate the opportunities available to a radiology practice considering opening a new office or show whether high-technology radiology is, as is widely assumed, an important factor in United States health costs. However, neither the total number of procedures nor their cost is known. We developed two largely independent estimates of each total (one based principally on surveys of radiologists, the other on Medicare data) to cross-validate the estimates and provide an indication of their uncertainty. We estimate that 260-330 million radiologic procedures were performed in the United States in 1990 (including both diagnostic and therapeutic procedures and radiologic procedures performed by nonradiologists) and that payments for these services totaled $19 to $22 billion (including payments for technical components in the hospital setting). This total was approximately 3.5% of national spending on personal health care; high-technology radiology totaled less than half of this amount. The procedures numbered 1.0-1.3 per capita annually, an increase of some 10-40% since 1980. Of the spending total, $10 to $12 billion was paid to physician practices, with a substantial portion of this amount going ultimately to practice expenses, particularly in the office setting. Our results suggest that spending on high-technology radiology is too small to be a major explanation for the current level of health costs in the United States. PMID- 1872248 TI - Is plagiarism ever insignificant? PMID- 1872249 TI - Effective audiovisual presentation: proper citation of sources. PMID- 1872250 TI - Sonography for mediastinal lymphoma. PMID- 1872251 TI - Inappropriate use of significant figures. PMID- 1872252 TI - Diagnosis of hemopericardium during digital subtraction angiography. PMID- 1872253 TI - Choledochal cyst and biliary atresia in the neonate. PMID- 1872254 TI - C-arm fluoroscopy. PMID- 1872255 TI - Videofluoroscopy in elderly patients with aspiration. PMID- 1872256 TI - A rare form of metatarsal synostosis. PMID- 1872257 TI - Subluxation of the humeral head associated with hemarthrosis in a patient with hemophilia. PMID- 1872258 TI - Paradoxical signals (short T2, long T2) in a patient with a soft-tissue tumor. PMID- 1872259 TI - Lateral meniscus pseudotear or "line of Murray". PMID- 1872260 TI - Programs and services for the deaf. III. University and college programs for personnel in deafness. PMID- 1872261 TI - Programs and services for the deaf. IV. Programs for the deaf-blind. PMID- 1872262 TI - Programs and services for the deaf. V. Supportive and rehabilitative programs for the deaf. PMID- 1872263 TI - Educational management of children with cochlear implants. AB - During the last decade, the technology of assistive hearing devices for hearing impaired children has improved significantly. Improvements in hearing aids and the introduction of cochlear implants and wearable tactile aids for children have made spoken language available to more deaf children and have changed the techniques for teaching listening and speaking skills. In June 1990, the Food and Drug Administration approved the Nucleus 22 channel cochlear implant for use with children. As a result, it is expected that more children will be implanted and, consequently, that the teachers and audiologist in the schools in which they are enrolled will need to learn to manage the devices. Since the Nucleus 22 cochlear implant does not restore normal hearing, children will continue to need instruction in listening and speaking. Furthermore, school personnel, who will be responsible for caring for and monitoring the implants, will have to learn how to maintain the devices. This article outlines some procedures for maximizing the benefits that profoundly deaf children can achieve with the cochlear implant. PMID- 1872265 TI - Programs and services for the deaf. II. Educational programs for deaf students. PMID- 1872264 TI - The development of a Children's Implant Profile. AB - The decision to provide a child with a cochlear implant is quite complex, as it must include consideration not only of the implant itself but also of the habilitative services necessary following the surgical procedure. To provide a systematic means of selecting hearing-impaired children for cochlear implants, a team at Children's Hearing Institute, Manhattan Eye, Ear and Throat Hospital, developed the Children's Implant Profile (ChIP). There is no one profile of a successful implant user--at least 11 factors appear to contribute to successful implantation. In the ChIP, each factor is evaluated on a three-point scale: (1) no concern, (2) mild-to-moderate concern, and (3) great concern. A profile showing "no concern" on all 11 factors denotes clear acceptability of the child as an implant candidate. A profile including several ratings in the "mild-to moderate concern" category suggests a need for further study to determine if improvements could be made in projected outcomes before initiating surgical procedures. Finally, ratings of "great concern," especially on more than one factor, indicate a very limited probability of successful implant outcomes, at least at the time of evaluation. A case study is presented to demonstrate the relationship between the evaluated factors and to show how the profile is used to address and remedy areas of concern. PMID- 1872266 TI - Effects of diltiazem on long-term outcome after acute myocardial infarction in patients with and without a history of systemic hypertension. The Multicenter Diltiazem Postinfarction Trial Research Group. AB - The effect of diltiazem on long-term outcome in patients with acute myocardial infarction with and without a history of systemic hypertension was investigated in 2,466 patients using the Multicenter Diltiazem Postinfarction Trial data-base. The baseline variables were comparable in the diltiazem and placebo-treated patients within the groups with and without hypertension. The initial 60-mg dose of diltiazem was associated with a significant (p less than 0.001) but modest (3%) reduction in blood pressure and heart rate in both groups with and without hypertension. Univariate and multivariate analyses revealed a meaningful overall reduction in first recurrent cardiac events (cardiac death or nonfatal reinfarction, whichever occurred first) and cardiac death in patients with hypertension treated with diltiazem compared with results in those treated with placebo. Similar effects were not observed in patients without a history of hypertension. When first recurrent cardiac events were used as the end point, the diltiazem:placebo hazard ratio (95% confidence limits) was 0.77 (0.58, 1.01) for the total hypertension group, and 0.67 (0.47, 0.96) and 1.32 (0.83, 2.10) for patients with hypertension with and without pulmonary congestion during the acute infarction, respectively. Similar results were observed using cardiac death as the end point. Beta blockers had a negligible effect on the hypertension diltiazem relation. These findings suggest that diltiazem may exert a long-term beneficial effect in most patients with hypertension who do not have pulmonary congestion during an acute infarction, and a detrimental effect in the minority who have pulmonary congestion. PMID- 1872267 TI - Comparison of the predictive characteristics of heart rate variability index and left ventricular ejection fraction for all-cause mortality, arrhythmic events and sudden death after acute myocardial infarction. AB - Heart rate (HR) variability index and left ventricular ejection fraction (EF) were compared for the prediction of all-cause mortality, arrhythmic events and sudden death in 385 survivors of acute myocardial infarction. For arrhythmic events, where, for a sensitivity of 75%, HR variability index had a specificity of 76%, EF had a specificity of only 45%. An EF of less than or equal to 40% had a sensitivity of 42% and a specificity of 75% for arrhythmic events; for the same sensitivity an HR variability index of 20 U had a specificity of 92%. An EF less than or equal to 40% had a sensitivity of 40% and a specificity of 73% for sudden death; HR variability index had a specificity of 83% for the same sensitivity. For all cause mortality, where, for a sensitivity of 75%, HR variability index had a specificity of 52%, EF had a specificity of 40%. It is concluded that HR variability index appears a better predictor of important postinfarction arrhythmic complications than left ventricular EF, but both indexes perform equally well in predicting all-cause mortality. PMID- 1872268 TI - Age-related normal values of signal-averaged electrocardiographic variables after acute myocardial infarction. AB - The study examined standard time domain variables of a signal-averaged electrocardiogram (SAECG) in 328 survivors of acute myocardial infarction. The correlation of these variables with age and the influence of age on the prediction of postinfarction arrhythmic complication (sudden death [n = 12] or sustained ventricular tachycardia, or both [n = 14]) from the SAECG were investigated. Statistically highly significant correlations (p less than or equal to 0.00002) between age and SAECG variables were found. Compared with patients aged less than 60 years, the SAECG-based stratification of arrhythmic complications after myocardial infarction in patients greater than 60 years had lower sensitivity for the same values of specificity and lower specificity for the same values of sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872269 TI - Non-Q- and Q-wave infarction after thrombolytic therapy with intravenous streptokinase for chest pain and anterior ST-segment elevation. AB - The clinical features of patients treated with streptokinase for chest pain and anterior ST-segment elevation who subsequently develop non-Q-wave infarction are unknown. Of the 75 consecutive patients who initially presented with chest pain and ST-segment elevation in the anterior leads (V1-V6, I, aVL) and were treated with intravenous streptokinase (time from symptoms to treatment averaged less than 3 hours), 32 (43%) developed a non-Q-wave and 43 (57%) a Q-wave myocardial infarction. Twenty seven of 32 patients (84%) from the non-Q-wave group and 39 of 43 (91%) from the Q-wave group were studied by angiography at 5.16 +/- 2.88 days after the onset of myocardial infarction. Left ventricular end-diastolic pressure was 13 +/- 6 vs 20 +/- 7 mm Hg (p less than 0.001), left ventricular ejection fraction was 60 +/- 8 vs 49 +/- 14% (p less than 0.001) and the infarct vessel patency rate was 85 vs 72% (p = 0.44) in patients with a non-Q versus a Q-wave infarction, respectively. In summary, when patients presenting with chest pain and ST-segment elevation are treated with streptokinase, a significant portion of these symptoms will evolve into a non-Q-wave infarction. Patients with a non-Q wave infarction will have a better preserved left ventricular function than patients who develop a Q-wave infarction. This suggests the need for equal distribution of such patients in randomized trials of thrombolytic therapy for acute myocardial infarction to avoid misinterpreting data between groups. PMID- 1872270 TI - Effects of urokinase and heparin on minimal cross-sectional area of the culprit narrowing in unstable angina pectoris. AB - The immediate and delayed effects of urokinase and heparin on minimal cross sectional area of a patent ischemia-producing coronary artery were prospectively investigated in 43 patients with unstable angina. After baseline angiography, patients were randomized to 3 different treatment groups: group I--urokinase (1,000,000 U intravenous bolus dose), followed by heparin infusion 3 hours later; group II--heparin (10,000 U intravenous bolus, followed by continuous infusion); and group III--conventional therapy only (intravenous nitroglycerin, beta blockers and calcium antagonists). Angiography was repeated at 1 hour and at 8 days of treatment and minimal cross-sectional area was determined in the 35 patients who completed the study. In group I, minimal cross-sectional area increased from 0.84 +/- 0.48 mm2 at baseline to 0.94 +/- 0.49 mm2 at 1 hour (p less than 0.05), and to 1.00 +/- 0.51 mm2 at 8 days (p less than 0.01 vs baseline). In group II, a significant increase in minimal cross-sectional area was observed only at the 8-day angiography (0.64 +/- 0.39 mm2 at baseline; 0.67 +/- 0.37 mm2 at 1 hour [p = not significant]; and 0.79 +/- 0.48 mm2 at 8 days [p less than 0.01] vs baseline). In group III, no significant changes in minimal cross-sectional area occurred either at 1 hour or at 8 days. Thus, both urokinase and heparin improved lesion geometry in patients with unstable angina, although a large individual variation was noticed. The effect occurred earlier with urokinase than with heparin. PMID- 1872271 TI - Twenty-four-hour activity of felodipine extended release in chronic stable angina pectoris. AB - To investigate the antiischemic efficacy and duration of action of the dihydropyridine calcium antagonist felodipine, 15 patients with stable exertional angina were enrolled in a double-blind, crossover study comparing 2 doses (5 and 10 mg) of felodipine extended release (ER) and placebo given once daily for 1 week. Bicycle exercise tests were repeated at the end of each treatment period 4 and 24 hours after dosing. Four hours after dosing with both felodipine doses, only 5 patients discontinued the exercise test because of greater than 2 mm of ST segment depression, whereas 10 continued until exhaustion (p less than 0.01 vs placebo). Compared with placebo, total exercise time was increased by 19% (p less than 0.001), with no difference between doses. After 24 hours, exercise duration was prolonged up to physical exhaustion in 6 patients taking felodipine 10 mg (p less than 0.05 vs both placebo and felodipine 5 mg); moreover, 11 patients taking 10 mg and 5 taking 5 mg increased time to 1 mm of ST depression greater than or equal to 15% compared with exercise time during the placebo test. Mean time to 1 mm of ST depression at 24 hours was increased by 8% with 5 mg and by 18% with 10 mg (p less than 0.001 vs placebo; p less than 0.01 between doses). Total exercise time at 24 hours was increased with both doses (p less than 0.001), with greater efficacy with the 10-mg dose (p less than 0.05 vs 5 mg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872272 TI - Ridogrel in the setting of percutaneous transluminal coronary angioplasty. AB - The safety of the combination of heparin and ridogrel therapy and its antiplatelet efficacy was examined in the setting of percutaneous transluminal coronary angioplasty (PTCA). In 32 patients without known aspirin intake for 10 days before PTCA, therapy with ridogrel (300-mg intravenous bolus) was begun just before PTCA and continued orally at a dose of 300 mg twice daily until discharge. Heparin was administered as a 10,000 IU bolus dose before PTCA and followed by an intravenous infusion at a rate of 1,000 IU/hour for 24 hours. Bleeding problems at the arterial entry site occurred in 13 patients, which required a blood transfusion in only 2 patients. One patient underwent emergency bypass surgery without specific problems of hemostasis. Ridogrel virtually eliminated thromboxane B2 from the serum (29,990 +/- 6,555 pg/0.1 ml before vs 63 +/- 7 pg/0.1 ml at 2 hours after ridogrel), with a concomitant increase in serum 6-keto prostaglandin F1 alpha (511 +/- 34 pg/0.1 ml before vs 1,190 +/- 146 pg/0.1 ml at 24 hours after ridogrel). There were no acute reocclusions in the ridogrel treated patients, whereas acute reocclusions occurred in 5.6% of the patients taking the standard aspirin + heparin regimen during the same period. Furthermore, at 6-month clinical follow-up patients treated with ridogrel compared favorably with those receiving standard treatment. PMID- 1872273 TI - Use of a morphologic classification to predict clinical outcome after dissection from coronary angioplasty. AB - To determine if morphology of procedure-associated dissections could help predict clinical outcome, angiograms of 691 coronary artery dissections resulting from percutaneous transluminal coronary angioplasty were categorized according to the National Heart, Lung, and Blood Institute classification system. Classes of dissection were then correlated with clinical outcome: 543 patients with type B dissections had no increase in morbidity and mortality when compared with patients without dissection, with a similar success rate of 93.7%. Complications in this group were low and compared favorably with complication rates in procedures not associated with dissection. One hundred forty-eight procedures associated with dissections of types C to F had a significant increase in in hospital complications, including acute closure (31%), need for emergency coronary bypass surgery (37%), myocardial infarction (13%) and repeat angioplasty (24%). The overall clinical success rate for those with types C to F dissection was 38%. The differences in clinical success and acute complications between type B and types C to F dissections were statistically significant at p less than 0.0005 for all variables studied. The angiographic morphology of a dissection during coronary angioplasty can predict clinical outcome, aiding in selection of effective therapy. PMID- 1872274 TI - Noninvasive identification of significant narrowing of the left main coronary artery by dipyridamole thallium scintigraphy. AB - To evaluate the usefulness of dipyridamole thallium scintigraphy with low-level exercise for the identification of left main (LM) coronary artery disease (CAD), 466 consecutive patients with CAD were studied. Thirty-eight patients (8%) had LM stenosis (diameter narrowing greater than or equal to 50%). The LM scintigraphic pattern was present in 9 of 38 patients with LMCAD and 38 of 428 CAD patients without LMCAD (24 vs 9%; p less than 0.005). This pattern was present in 6 of 9 patients with LMCAD without right CAD and in only 3 of 29 patients with LM and right CAD (67 vs 10%; p = 0.0005). Patients with LMCAD had a higher incidence of premature cessation of low-level exercise (53 vs 21%; p less than 0.0001), chest pain (68 vs 48%; p less than 0.02), blood pressure decrease of greater than or equal to 20 mm Hg (44 vs 16%; p less than 0.002) and greater ST depression (0.17 +/- 0.13 vs 0.06 +/- 0.10 mV; p less than 0.001) during dipyridamole loading than patients without LMCAD. Stepwise discriminant analysis revealed that the LM scintigraphic pattern and markers of ischemia during dipyridamole loading best identified (p less than 0.0001) patients with LMCAD without right CAD (sensitivity 67%, specificity 91%), but this predictability is no better than the LM scintigraphic pattern alone. The combination of clinical markers of ischemia during dipyridamole loading and scintigraphic findings of diffuse slow washout, extensive fixed defects and the LM pattern best identified (p less than 0.0001) patients with LM and right CAD (sensitivity 72%, specificity 80%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872275 TI - Evaluation of dipyridamole-Doppler echocardiography for detection of myocardial ischemia and coronary artery disease. AB - Doppler assessment of left ventricular filling and ejection during dipyridamole stress may supplement wall motion analysis for detection of myocardial ischemia and coronary artery disease (CAD). Thirty-four patients taking no cardioactive therapy were studied using intravenous dipyridamole (0.6 mg/kg) during 2 dimensional and pulsed Doppler echocardiography. Twelve patients had normal coronary arteries (group 1) and the remainder, who had significant CAD, were divided into groups 2 (n = 11) and 3 (n = 11). Only subjects in group 2 developed myocardial ischemia manifest as reversible regional asynergy and ST-segment depression. Heart rate increased (16 +/- 9 beats/min, p less than 0.01) and mean blood pressure decreased (-5 +/- 8 mm Hg, p = not significant) uniformly across groups. Exaggerated hyperkinesia of normally contracting wall segments was the common response to dipyridamole infusion in patients with CAD. The respective mean percent changes in peak early diastolic velocity, peak atrial velocity, their ratio and ejection peak velocity, and mean acceleration for groups 1 (20, 42, -13, 20 and 23%), 2 (22, 32, -2, 10 and 14%) and 3 (23, 33, -6, 16 and 18%) were similar. Comparisons between normal patients and those with CAD and between groups 2 and 3 revealed no significant differences in the effect of dipyridamole on any variable. However, a decrease in both peak velocity and mean acceleration of left ventricular ejection was seen in 3 of 4 group 2 patients who developed severe ischemia. Dipyridamole-Doppler echocardiography is insensitive for detection of CAD and appears unable to identify myocardial ischemia unless this is severe. Hemodynamic changes and compensatory wall motion induced by dipyridamole may explain these findings. PMID- 1872276 TI - Pronounced reduction of aortic flow velocity and acceleration during heavy isometric exercise in coronary artery disease. AB - Doppler-derived parameters of aortic flow were examined during heavy isometric exercise in 48 men with coronary artery disease (CAD) and in 48 gender- and age matched healthy controls. The aim was to determine which parameters best separated the groups and to look for a possible relation between exercise-induced Doppler patterns and the extent of CAD. Isometric exercise was performed with a 2 hand bar dynamometer, and the subjects were required to perform 50% of maximal voluntary contraction for 2 minutes. Examination was performed with a pulsed Doppler transducer positioned at the suprasternal notch. Resting peak flow velocity, acceleration time, stroke volume index and cardiac index did not show significant differences between the groups. However, mean acceleration and stroke work were significantly lower in patients with CAD. In this group, exercise peak flow velocity decreased from 98 +/- 13 to 55 +/- 12 cm/s, flow velocity integral from 14 +/- 3 to 7 +/- 3 cm, mean acceleration from 11 +/- 0.9 to 4.7 +/- 1 m/s/s, and stroke volume index from 41 +/- 6 to 23 +/- 4 ml/m2 (p less than 0.001 for all). Cardiac index decreased from 2.7 +/- 0.4 to 2 +/- 0.2 liters/min/m2 (p less than 0.05). Acceleration time increased from 82 +/- 6 to 116 +/- 7 ms. In most of the indexes, the directional changes induced by isometric exercise were similar in patients with CAD and in normal control subjects. The differences compared with the rest values were significantly greater in the CAD group, and especially in patients presenting with 3-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872277 TI - Usefulness of excitable gap and pattern of resetting in atrial flutter for determining reentry circuit location. AB - Clinical and experimental data show that type I atrial flutter is due to a reentry mechanism with an excitable gap. To define the location of the reentry circuit of atrial flutter, width of excitable gap, poststimulation cycle and pattern of reset after premature stimulus were analyzed in 18 patients during atrial flutter at multiple atrial sites (high, lateral, posterior and septal right atrium, and coronary sinus). The pattern of reset was defined as flat or increasing whether the return cycle remained unchanged or prolonged with increasing prematurity. Shorter values of the excitable gap were found at the coronary sinus (33 +/- 8 ms) and high right atrium (30 +/- 10 ms) than at the posterior (43 +/- 9 ms) or septal right atrium (45 +/- 11 ms). Intermediate values (36 +/- 8 ms) were measured at the lateral right atrium. Poststimulation cycle, corrected for atrial flutter cycle length, was shorter in the posterior (6 +/- 7 ms) and septal right atrium (5 +/- 7 ms) than in the coronary sinus (35 +/- 9 ms), and the high (23 +/- 10 ms) and lateral right atrium (15 +/- 9 ms). A flat pattern of resetting occurred more frequently at the septal (18 of 18 patients) and posterior right atrium (15 of 18) than at the lateral (8 of 18) and high right atrium (2 of 17), and was never observed at the coronary sinus. Atrial flutter was successfully terminated by overdrive atrial pacing in 15 of 18 patients, and termination was more easily obtained from the septal and posterior right atrium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872278 TI - Effects of exercise on heart rate, QT, QTc and QT/QS2 in the Romano-Ward inherited long QT syndrome. AB - Patients with the Romano-Ward inherited long QT syndrome have an incompletely defined cardiac sympathetic system abnormality, and exhibit ventricular arrhythmias during exercise, fear and anxiety. Treadmill and bicycle exercise were used to modulate cardiac autonomic activity in 27 Romano-Ward subjects and 27 normal controls. The heart rate, and the QT, QTc and QT/QS2 (ratio of electrical to mechanical systole) intervals were compared. Subjects with long QT were compared with normals. Those with a long QT interval had the following results: similar resting heart rates; lower rates during moderate (151.6 vs 169.6 beats/min, p = 0.04) and maximal (155.9 vs 182.1 beats/min, p = less than 0.001) exercise; an abnormal QT cycle-length relationship, with failure of the QT to shorten normally with increasing heart rate; an increase in QTc versus a decrease in normals; supine rest QT/QS2 ratio of 1.12 vs 0.93, p = 0.001; and an exercise QT/QS2 that increased by 30%, from 1.12 at rest to 1.45, versus 15%, in normals, from 0.93 to 1.07, p = 0.001. The lower heart rates and excessively prolonged QT/QS2 ratios during exercise further support an abnormality of, or abnormal cardiac response to, sympathetic activity. A QT/QS2 greater than 1.0 at rest, an exercise QT/QS2 ratio greater than 1.17, and an increase in QTc during moderate exercise may be helpful diagnostic findings in patients with borderline long QTc intervals at rest. PMID- 1872279 TI - Improved specificity of myocardial thallium-201 single-photon emission computed tomography in patients with left bundle branch block by dipyridamole. AB - Reduced septal uptake of thallium-201 during exercise is frequently observed in patients with left bundle branch block (LBBB) and normal coronary arteries. This may reflect normal coronary autoregulation in response to lower septal oxygen demand; thus, dipyridamole, which uniformly exploits flow reserve, would be more accurate for diagnosis of coronary artery disease (CAD). Sixteen patients with LBBB underwent exercise and dipyridamole thallium-201 single-photon emission computed tomography and coronary angiography within 3 months. Sensitivity for detection of left anterior descending CAD (greater than 50% stenosis) was 0.83 for exercise and 1.00 for dipyridamole. Specificity was 0.30 (visual) or 0.20 (quantitative analysis) for exercise and 0.80 (visual) or 0.90 (quantitative) for dipyridamole (p less than 0.05). Dipyridamole combined with quantitative analysis also improved specificity of CAD detection overall (p less than 0.01). These data demonstrate that pharmacologic vasodilation is more accurate than exercise when diagnosing CAD by myocardial perfusion scintigraphy in patients with LBBB. PMID- 1872280 TI - Use of Valsalva maneuver to unmask left ventricular diastolic function abnormalities by Doppler echocardiography in patients with coronary artery disease or systemic hypertension. AB - It has been suggested that changes in left atrial pressure may mask or mimic left ventricular diastolic function abnormalities detected by Doppler echocardiography. The effect of the Valsalva maneuver on the transmitral flow velocity profile was therefore studied in 28 patients without evidence of coronary artery disease (group 1, mean age +/- standard deviation 50 +/- 8 years) and in 94 patients with evidence of coronary artery disease or systemic hypertension (group 2, mean age 54 +/- 10 years). At baseline, group 2 patients had higher peak late diastolic filling velocity (A), lower peak early (E) to late diastolic filling velocity (E/A) ratio and longer isovolumic relaxation time than group 1, whereas heart rate, E velocity and E deceleration time were similar in both groups. During Valsalva, both groups had similar increases in heart rate and similar decreases in E velocity but E/A ratio decreased significantly only in group 2 because of a lesser decrease in A velocity. The E/A ratio was greater than or equal to 1.0 both before and during Valsalva in all but 1 patient in group 1, whereas in group 2, 32 patients had E/A greater than or equal to 1.0 at rest and during Valsalva, 33 patients had E/A greater than or equal to 1.0 at rest but less than 1.0 both at rest and during Valsalva. Using group 1 as controls, prevalence, specificity and positive predictive value of E/A less than 1.0 in group 2 were 31, 100 and 100% at rest and 66, 96 and 98% during Valsalva.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872281 TI - Electrocardiographic correlates of reperfusion status after thrombolysis: is the "incomplete" or "interrupted" infarction a non-Q-wave infarction? PMID- 1872282 TI - Spasm and arterial injury. PMID- 1872283 TI - Edge detection versus videodensitometry for quantitative angiographic assessment of directional coronary atherectomy. PMID- 1872284 TI - Effects of parasympathetic blockade on ischemic threshold in patients with exercise-induced myocardial ischemia. PMID- 1872285 TI - Long-term follow-up after intracoronary ethanol ablation of atrioventricular conduction. PMID- 1872286 TI - Actuarial risk of sudden death while awaiting cardiac transplantation in patients with atherosclerotic heart disease. DEFIBRILAT Study Group. PMID- 1872287 TI - Aging and left ventricular function in elderly healthy people. PMID- 1872288 TI - Influence of Doppler sample volume location on ventricular filling velocities. PMID- 1872289 TI - Independent effects of low frequency magnitude and phase distortion on the recorded electrocardiogram. PMID- 1872290 TI - Validation of a bedside method of activated partial thromboplastin time measurement with clinical range guidelines. PMID- 1872291 TI - Cardiac transplantation for giant coronary artery aneurysms complicating Kawasaki disease. PMID- 1872292 TI - Transesophageal echocardiographic findings of papillary muscle rupture. PMID- 1872293 TI - Should antibiotic prophylaxis be recommended for all patients with mitral valve prolapse? PMID- 1872294 TI - Angiographic progression to total coronary occlusion in hyperlipidemic patients after acute myocardial infarction. PMID- 1872295 TI - Lipid profiles after cardiac transplantation. PMID- 1872296 TI - Radionuclide exercise response in young asymptomatic chronic alcoholics. PMID- 1872297 TI - Cause of ventricular arrhythmia. PMID- 1872298 TI - Mitral regurgitation improves when aortic valve area increases significantly. PMID- 1872299 TI - Oral treatment of diabetes mellitus: the contribution of gliclazide. PMID- 1872300 TI - Oral treatment of diabetes mellitus: the contribution of gliclazide. Proceedings of a symposium, September 23, 1989, Lisbon, Portugal. PMID- 1872301 TI - Hepatic sensitivity to insulin: effects of sulfonylurea drugs. AB - Insulin regulation of hepatic glucose production (HGP) is altered in non-insulin dependent diabetes mellitus (NIDDM), resulting in increased glucose output by the liver; this contributes to the elevation in plasma glucose concentration observed both in the basal state and postprandially. Therefore, restoration of normal insulin action in the liver must be a goal of hypoglycemic therapy. Sulfonylureas have been widely used for treatment of NIDDM over the past 30 years. In addition to their stimulatory effect on insulin secretion, these compounds seem to possess extrapancreatic effects. Early in vitro studies showed that addition of sulfonylureas to the perfusion medium of liver preparations could exert a significant suppressive effect on HGP. Subsequent experience suggested that these compounds could act at the level of the insulin receptor as well as at various postreceptor sites. These studies showed that sulfonylureas may inhibit glycogenolysis and gluconeogenesis while stimulating glycogen synthesis. Results obtained in vivo in NIDDM patients are in agreement with the in vitro studies. Long-term treatment with sulfonylureas is associated with a decline in fasting plasma glucose concentration and a parallel reduction in HGP. Nevertheless, the direct effect of sulfonylurea administration on the liver remains unclear, since the reduction in HGP that occurs during sulfonylurea treatment may be secondary to an overall improvement in insulin secretion. It is also of interest that in insulin-dependent diabetic patients, sulfonylurea administration in combination with insulin injections is not followed by a significant change in HGP. Possible effects of sulfonylureas on glucagon secretion and on the metabolism of free fatty acids (FFAs) may also contribute to improved sensitivity of the liver to the suppressive action of insulin, since these agents appear to reduce plasma glucagon and FFA concentrations. Thus, present data support an extrapancreatic action of sulfonylureas on the liver. However, it does appear that a certain degree of residual insulin secretion is required for sulfonylurea agents to elicit their hepatic effect. PMID- 1872302 TI - Current status of non-insulin-dependent diabetes mellitus (type II): management with gliclazide. AB - Non-insulin-dependent diabetes mellitus (NIDDM) is a major cause of morbidity and mortality worldwide, with a prevalence of 3-7% in most Western countries. Decreased insulin secretion and diminished tissue insulin sensitivity are both implicated in the pathogenesis of the disease; both may be exacerbated by persistent hyperglycemia and improved by normalization of blood sugar levels. Measures to control hyperglycemia, hypertension, and hyperlipidemia are important in the management of NIDDM and prevention of its long-term complications. The effects of dietary modification, exercise, and antihypertensive and antiplatelet therapy, as well as of pharmacologic control of blood sugar, on the vascular and renal complications of NIDDM have been investigated. Gliclazide is a second generation sulfonylurea drug whose efficacy in the treatment of NIDDM, alone or in combination with insulin, has been widely demonstrated. Studies of the use of gliclazide, reported at recent symposia, are summarized in this review. PMID- 1872303 TI - Effect of 6-month gliclazide treatment on insulin release and sensitivity to endogenous insulin in NIDDM: role of initial continuous subcutaneous insulin infusion-induced normoglycemia. AB - In 10 obese, new-onset non-insulin-dependent diabetes mellitus (NIDDM) patients (group A), continuous subcutaneous insulin infusion (CSII) was used to induce normoglycemia during 14 days. Fasting blood glucose was 4.6 +/- 0.2 mmol/L and mean daily blood glucose 5.8 +/- 0.2 mmol/L at the end of the CSII period. This excellent glycemic control was obtained with 35 +/- 4.8 U of insulin per day, corresponding to 0.47 +/- 0.06 U/kg/24 hours. Endogenous insulin production was markedly suppressed, since urinary C-peptide was reduced from 18.5 +/- 0.12 to 7.9 +/- 0.25 nmol/24 hours. Gliclazide was given to group A following CSII, and to five obese NIDDM patients (group B) in their habitual hyperglycemic state. Gliclazide maintained in group A, and induced in group B, excellent metabolic control. This was accompanied by the appearance of a small first-phase insulin response to intravenous glucose, and significant increases in the mean-daily insulin to mean-daily-blood-glucose ratio, as well as in the 24-hour urinary C peptide-to-glucose ratio. The gliclazide effects tended to be more pronounced in group A. No significant effect was seen on efficacy of endogenous insulin (slope of disappearance of blood glucose divided by insulin levels). During 6 months of gliclazide treatment, excellent glycemic control was maintained in all patients. This was paralleled by unchanged stimulation by gliclazide of first-phase insulin response to glucose, and augmented mean 48-hour insulin-to-glucose and urinary C peptide-to-glucose ratios. No change in the ratio of glucose disposal to endogenous insulin was noted. We conclude that physiologic insulin replacement may induce normoglycemia in NIDDM, indicating that insulin resistance is not of clinical significance; gliclazide has a beta-cell-stimulating action that is maintained quantitatively unchanged for at least 6 months; the therapeutic effect of gliclazide in NIDDM seems to be mainly, if not exclusively, the result of its beta-cytotrophic action. Initial normoglycemia, induced here by CSII, may have a lasting enhancing effect on the gliclazide action. PMID- 1872304 TI - An evaluation of long-term glycemic control in non-insulin-dependent diabetes mellitus: the relevance of glycated hemoglobin. AB - Thirty-six patients were admitted to an open study designed to evaluate the long term efficacy of gliclazide in the treatment of type II diabetes mellitus. Results from 27 of these patients were analyzed at 36 months, 21 at 48 months, and 16 at 60 months of follow-up. An overall reduction in fasting and postprandial blood sugar was observed (p less than 0.001). Total glycated hemoglobin (HbA1) fell significantly (p less than 0.001), to revert to values within the reference range in over 80% of cases. Body weight remained stable over a period of observation ranging from 36 to 60 months. The incidence of subsequent failure of oral treatment was 2% per annum. These results show that long-term treatment of type II diabetes with gliclazide leads to satisfactory results, with practically no side effects. PMID- 1872305 TI - Pathophysiology of vascular disease in diabetes: effects of gliclazide. AB - Diabetes mellitus is a major risk factor for coronary heart disease, peripheral vascular disease, and cardiovascular disease. The prevalence of these complications is increased about two- to four-fold in people with diabetes in the United States, and they contribute substantially to morbidity, mortality, and healthcare costs. The pathogenesis of macrovascular disease in diabetes is multifactorial. Endothelial injury is an early event, followed by macrophage adherence and uptake of lipids to produce a fatty streak. Platelet adherence, aggregation, and release of thromboxane and platelet-derived growth factors may then occur. Quantitative and qualitative alterations of lipoproteins are seen, particularly in uncontrolled insulin-dependent and non-insulin-dependent diabetes. Hyperinsulinemia may be contributory, as may elevated plasma proinsulin levels. Glycation of plasma proteins and of components of the vascular wall occurs, and altered coagulation and/or fibrinolysis may lead to thrombosis. The process is accelerated by hypertension, smoking, and hypercholesterolemia. Gliclazide is an oral sulfonylurea agent that has been reported to have actions on platelet function and fibrinolysis in addition to its effects on glycemia. The evidence for this is reviewed, and recommendations for future studies are made. PMID- 1872306 TI - Development of macroangiopathy in sand rats (Psammomys obesus), an animal model of non-insulin-dependent diabetes mellitus: effect of gliclazide. AB - The risk of developing macroangiopathy associated with diabetes led us to study in sand rats the long-term consequences of non-insulin-dependent diabetes on the development of arterial lesions promoted by feeding a high-cholesterol diet. Gliclazide, an agent whose preventive effect has previously been suggested in other experimental models of atheroma, was also investigated in these diabetic and hypercholesterolemic animals. Sand rats were fed a natural diet (ND group), a standard laboratory feed (StD group), or a high-cholesterol feed (HCD group) for 15 months. Biologic parameters were monitored throughout the period of the study, and histologic and histochemical examinations were conducted when the animals were killed (month 15). One StD group and one HCD group were treated with gliclazide from month 3 to month 15. The StD group developed a syndrome of obesity, hyperglycemia, hyperinsulinemia, and triglyceridemia. The high cholesterol feed further increased hypercholesterolemia. These biologic abnormalities were accompanied by arterial lesions (thickening of the intima, deposition of glycosaminoglycans). Foam cells were seen in the intima, and microthrombi were present in the lumen of the arteries of animals in the HCD group. Long-term gliclazide medication at doses that normalized serum glucose levels also reduced the obesity, hyperinsulinemia, lipid disorders, and it prevented or retarded the appearance of arterial lesions. PMID- 1872307 TI - Pathogenesis of diabetic microangiopathy: an overview. AB - Major susceptibility factors for diabetic microangiopathy include duration of disease and probably quality of metabolic control. The mechanism of development of microangiopathy is incompletely understood but appears to involve functional abnormalities within the microcirculation, enhanced glucose metabolism, hemostatic abnormality, and genetic susceptibility. This article reviews the factors believed to be involved in pathogenesis and attempts to draw these together by suggesting a sequence of pathogenic interactions that could result in the microvascular changes seen in susceptible target organs. Possibilities for therapeutic intervention based on these pathogenic mechanisms are discussed. A small pilot trial of an oral hypoglycemic agent, gliclazide, is reported, providing evidence for a specific action of this drug on thromboxane synthesis and platelet aggregation. This is independent of glycemic control and may in part be mediated by a fall in lipid peroxides. PMID- 1872308 TI - Diabetic retinopathy in non-insulin-dependent diabetes mellitus patients: the role of gliclazide. AB - Diabetic retinopathy is the most common cause of human blindness between the ages of 30 and 67 in the industrialized world. Retinopathy has a multifactorial etiology. Standard treatment has aimed at correcting only disturbed glucose metabolism, but this may lead only to the partial amelioration of certain hemobiologic factors. In addition to its metabolic action, gliclazide has been shown to have specific hemobiologic properties; studies with gliclazide in animals and humans have shown significant improvements of platelet abnormalities, stimulation of prostaglandin I2 synthesis, and enhancement of fibrinolytic activity. In humans, open-label studies have shown that gliclazide treatment leads to stabilization of background retinopathy in non-insulin-dependent diabetics and, more recently, these beneficial effects have been confirmed in controlled studies lasting up to 37 months in which other sulfonylureas were used. The Japanese Diabetic Retinopathy Program studied the progression of retinopathy over a 5-year period, comparing gliclazide with other sulfonylureas and with placebo. This study showed that, with equivalent metabolic control, there was a trend toward a lower rate of deterioration and a significantly lower incidence of preproliferative retinopathy in the group receiving gliclazide compared with those receiving other sulfonylureas. Overall, the specific hemobiologic actions of gliclazide appear to offset or retard the progression of diabetic retinopathy and may have the advantage of lowering the incidence of preproliferative retinopathy. PMID- 1872309 TI - Rationale for the association of sulfonylurea and insulin. AB - Approximately 20-30% of patients with non-insulin-dependent diabetes mellitus (NIDDM) started on sulfonylureas fail to respond to treatment (primary failure); in the remaining patients, secondary failure to sulfonylurea therapy occurs at a rate of 5-10% per year. On the other hand, in insulin-treated NIDDM patients a progressive increase in insulin requirement can occur without significant improvement in glucose control. In these patients the combination of oral agents with insulin therapy may be useful. The rationale behind this therapeutic approach resides in the synergistic action of the two agents on specific mechanisms responsible for glucose intolerance and hyperglycemia. Long-acting insulin, administered as a single dose at supper or bedtime, should restrain excessive overnight hepatic glucose production, thus allowing a significant reduction in fasting glucose concentrations. A lower ambient glucose level should favor the stimulatory effect of sulfonylureas on insulin secretion. Sulfonylurea treatment should increase the portal inflow of secreted insulin with a resultant increase in insulin levels draining into liver, thus reducing postprandial hepatic glucose output. Moreover, sulfonylureas might improve insulin action on its target tissue (i.e., muscle), thus increasing overall insulin-mediated glucose metabolism. The reduction in prevailing plasma glucose levels will reduce the toxic effect of hyperglycemia on the beta-cell and on insulin-sensitive tissues. On this basis, NIDDM patients with secondary failure of monotherapy may benefit from combined therapy. Nevertheless, the effects of combined therapy should be strictly monitored and intensive insulin therapy promptly started if poor control persists. PMID- 1872310 TI - Mechanisms for hyperglycemia in type II diabetes mellitus: therapeutic implications for sulfonylurea treatment--an update. AB - Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by fasting hyperglycemia associated with defects in the pancreatic islet, the liver, and the peripheral tissues, which together comprise a feedback loop responsible for maintenance of glucose homeostasis. This review focuses on the key role of the endocrine pancreas alpha and beta cells to coordinate glucose output from the liver with glucose utilization. The basal rate of hepatic glucose utilization. The basal rate of hepatic glucose production is elevated in subjects with NIDDM, and this is positively correlated with the degree of fasting hyperglycemia. This increased rate of glucose release by the liver results from impaired hepatic sensitivity to insulin, reduced insulin secretion, and increased glucagon secretion. Though basal immunoreactive insulin levels in patients with NIDDM may appear normal when compared with healthy individuals, islet function testing at matched glucose levels reveals impairments of basal, steady-state, and stimulated insulin secretion due to a reduction in beta-cell secretory capacity and a reduced ability of glucose to suppress glucagon. The degree of impaired beta-cell responsiveness to glucose is closely related to the degree of fasting hyperglycemia but in a curvilinear fashion. The efficiency of glucose uptake by the peripheral tissues is also impaired due to a combination of decreased insulin secretion and defective cellular insulin action. This impairment becomes more important to the hyperglycemia as the islet alpha- and beta-cell function declines. Therapeutic interventions, to be effective, must reduce hepatic glucose production either by improving islet dysfunction and raising plasma insulin levels, or improving the effectiveness of insulin on the liver. Both result in a decline in the fasting glucose levels regardless of the cause of hyperglycemia. We conclude that NIDDM is characterized by a steady-state re-regulation of plasma glucose concentration at an elevated level in which islet dysfunction plays a necessary role. Treatment should be based on this physiologic understanding. PMID- 1872311 TI - Combination of insulin and sulfonylureas: a literature review. PMID- 1872312 TI - Majority of RNs favor mandatory testing for AIDS. PMID- 1872314 TI - Faculty nurtures, too. PMID- 1872313 TI - The use--and abuse--of negative thinking. PMID- 1872315 TI - The PIC catheter: a different approach. PMID- 1872317 TI - Psychoneuroimmunology. PMID- 1872316 TI - Awakening the inner healer. PMID- 1872318 TI - Caring for the morbidly obese. PMID- 1872320 TI - Carolinas jobfocus. Careers in the Carolinas. PMID- 1872319 TI - Mid-Atlantic job focus. Wellness for women. PMID- 1872321 TI - ANA members say no to mandatory AIDS testing, vote to require BSN for certification by 1998. PMID- 1872322 TI - Our shield: competence with compassion. PMID- 1872323 TI - Fifty-third annual meeting of the South Atlantic Association of Obstetricians and Gynecologists. Hot Springs, Virginia, January 27-30, 1991. PMID- 1872324 TI - Characterization of in vitro chemosensitivity of perioperative human ovarian malignancies by adenosine triphosphate chemosensitivity assay. AB - We report the in vitro chemosensitivity of primary and recurrent human ovarian tumor samples analyzed by adenosine triphosphate chemosensitivity assay. We defined sensitivity as a greater than or equal to 70% decrease in intracellular adenosine triphosphate versus control at 20% of the reported peak plasma concentration per agent tested. Twenty of 21 assays (95.24%) were completed successfully. Single-agent and combined dose-response patterns consisting of decreasing viability with increasing drug concentration were observed consistently. Thirteen primary tumors were assayed, with 15.4% sensitive to cisplatin, 7.7% sensitive to 4-hydroxycyclophosphamide and 53.8% sensitive to their combination. Seven recurrent tumors were assayed, with 14.3% sensitive to cisplatin, 28.6% sensitive to 5-fluorouracil, and 42.9% sensitive to their combination. Dose-response characteristics and in vitro sensitivity rates reported in this article are consistent with reports of patient response in the literature. We conclude that adenosine triphosphate chemosensitivity assay is an efficient and reliable instrument for the in vitro chemosensitivity assessment of human tumors and warrants further clinical investigation. PMID- 1872325 TI - Single-center comparison of results of 1000 prenatal diagnoses with chorionic villus sampling and 1000 diagnoses with amniocentesis. AB - Large multicenter studies have confirmed the safety and accuracy of chorionic villus sampling as a prenatal genetic diagnostic procedure, but there have been few single-center evaluations. We report our experience with 1000 consecutive chorionic villus sampling procedures compared with 1000 consecutive amniocentesis procedures during the same period. The procedures were performed by the same genetic counselors, sonographers, obstetricians, and laboratory personnel. Indications for referral, demographic characteristics of patients, numbers of attempts per patient, fetal loss rates, laboratory results, and evaluation of accuracy are included. Analysis of all data suggests that chorionic villus sampling is a safe and accurate alternative to amniocentesis in our community based teaching hospital. PMID- 1872326 TI - Quantification of cervical change: relationship to preterm delivery in the multifetal gestation. AB - Prematurity is the major contributor to the very high perinatal morbidity and mortality associated with multifetal gestations. Antepartum cervical evaluation has been suggested as a way to better define the risk of preterm delivery in multifetal gestations. Weekly digital cervical examinations were performed in 86 twin and 7 triplet gestations that were being monitored in a special antepartum clinic. A cervical score was calculated from each examination by subtracting cervical dilatation in centimeters from cervical length in centimeters. Cervical scores decline gradually with advancing gestation and are influenced by parity and subsequent preterm delivery. Intervals until delivery decrease significantly with lower cervical scores. A cervical score less than or equal to 0 on or before 34 weeks' gestation was strongly predictive of preterm delivery (75%). Only 2 of 78 (2.6%) with a score greater than 0 were delivered within 1 week of the examination. Cervical scoring is a simple, quantifiable, reproducible, and safe method of evaluating preterm delivery risk. An understanding of the prognostic significance of specific cervical scores may be of value in determining the need for obstetric intervention. PMID- 1872327 TI - Appropriateness of intrapartum fetal heart rate management and risk of cerebral palsy. AB - Cerebral palsy affects 2 in 1000 infants in the United States, and the intrapartum period is frequently scrutinized as the etiologic source. In a matched group of 49 infants with cerebral palsy at 1 year of age and 49 controls, no difference in the incidence of inappropriate intrapartum fetal heart rate pattern management was detected. This supports the conclusions of others that the intrapartum period is an infrequent source of cerebral palsy. PMID- 1872328 TI - Combined interferon alfa and doxorubicin in the treatment of advanced cervical cancer. AB - Interferon alfa and doxorubicin have been shown to have synergistic effects when tested in vitro with cells derived from cervical cancers. A clinical trial was designed, testing interferon alfa plus doxorubicin in patients with advanced or recurrent cervical cancers. Twenty-one patients were given interferon alfa, 10 million units per square meter intramuscularly and 10 million units per square meter intravenously over a 30-minute infusion period. One hour later 20 mg/m2 doxorubicin was given intravenously slowly over a 2-hour period. Treatments were repeated once weekly for 3 weeks. Initial response evaluation was done at week 5, and treatment was continued on an every-other-week schedule for patients showing favorable responses or stable disease. Bone marrow, hepatic, and renal toxicities were minimal. Fever and malaise were the major sources of toxicity. Of the 17 evaluable patients, six had clinical partial responses. Two of the responders have enjoyed more than 5 years' survival. This regimen is well tolerated and does have efficacy in some patients with advanced cervical cancers. PMID- 1872329 TI - Primary invasive vaginal carcinoma. AB - A review of primary vaginal carcinoma treated at the Medical University of South Carolina from January 1970 through December 1989 included 76 squamous carcinomas, 12 adenocarcinomas, and 3 undifferentiated carcinomas. Staging was done according to the system of the International Federal of Gynecology and Obstetrics as modified by Perez et al. Stages I, II, III, and IV included 25, 39, 15, and 12 patients, respectively. Corrected 5-year survival rates were 73% for stage I, 39% for stage II, 38% for stage III, and 25% for stage IV. Sixteen percent of patients had received prior pelvic radiation. Invasive cervical cancer preceded vaginal cancer in 21% of patients. Detection of cancer was accomplished by routine cytologic testing in 17% of patients, palpation of an asymptomatic mass in 10% of patients, or palpation of a symptomatic mass in 72% of patients. Eighty seven percent of patients were treated with radiation therapy. Survival curves of patients grouped by stage and other potential prognostic factors were compared. Lower stage (p less than 0.01), younger age (p less than 0.02), and no symptoms at detection (p less than 0.01) were statistically significant favorable prognostic factors. Histologic type, extent of vaginal involvement, vaginal location, prior radiation therapy, prior cervical cancer, and prior hysterectomy are factors that did not significantly affect survival. PMID- 1872330 TI - Analysis of 500 obstetric and gynecologic malpractice claims: causes and prevention. AB - Five hundred obstetric and gynecologic malpractice litigation claims were analyzed to determine the incidence of claims that could not be defended because of breach of standards of care, problems with documentation, or both. Of the 500 claims, 294 were obstetric and 206 were gynecologic. Of the obstetric claims, 79 (27%) were indefensible because of breaches of standards of care (71%), problems with documentation (5%), or both (24%). Of the 206 gynecologic claims, 45 (22%) were indefensible because of breaches of standards of care (62%), problems with documentation (24%), or both (13%). The incidence of indefensible obstetric and gynecologic claims was 25%. Indefensible claims were analyzed to determine the common medical and surgical problems that instigated the malpractice suits. Recommendations are made that should reduce the incidence of indefensible malpractice suits. PMID- 1872331 TI - Changes in lipids and lipoproteins with long-term estrogen deficiency and hormone replacement therapy. AB - Cross-sectional data of the long-term effects of estrogens, androgens, and progestogens on lipids and lipoproteins were obtained in 556 postmenopausal women aged 24 to 85 years with follow-up for 1 to 44 years. Baseline values were obtained in 155 women from less than 1 year up to 30 years after menopause. Total cholesterol and low-density lipoprotein cholesterol tended to rise during the early postmenopausal years while high-density lipoprotein cholesterol did not change. Triglycerides were related to weight and were significantly different only between untreated women of normal weight (128.3 +/- 7.80 mg/dl) and hormone users weighing greater than 200 pounds (252.9 +/- 9.44 mg/dl), p less than or equal to 0.001. Although mean high-density lipoprotein cholesterol was lower with both C-21 progestogens (64.5 +/- 4.16 mg/dl) and C-19 progestogens (61.9 +/- 3.84 mg/dl), there were no statistically significant differences on comparison with levels in the unopposed estrogen users (67.0 +/- 3.94 mg/dl). Smoking significantly depressed high-density lipoprotein cholesterol in both hormone users (p less than or equal to 0.001) and untreated women (p less than or equal to 0.001). Added progestogens do not adversely affect lipids and lipoproteins over the long term when adequate dosages of estrogens are used. PMID- 1872332 TI - Endometrial morphology in asymptomatic postmenopausal women. AB - Few data are available regarding endometrial histologic features in asymptomatic perimenopausal and postmenopausal women. This study encompasses endometrial biopsy specimens obtained from 801 such women before enrollment in a multicenter study of estrogen-progestin replacement. One endometrial cancer was found (0.13%); four additional biopsy specimens showed atypia (total 0.63%). The endometrium was atrophic in 373 (46.9%), proliferative in 133 (16.7%), secretory in 54 (6.8%), and hyperplastic in 41 (5.2%). Insufficient tissue for diagnosis was obtained in 195 (24.5%). We conclude that the yield for neoplasia is so low that screening endometrial biopsy is not justified in asymptomatic perimenopausal and postmenopausal women. PMID- 1872333 TI - Assessment of Kegel pelvic muscle exercise performance after brief verbal instruction. AB - Forty-seven women had urethral pressure profile determinations performed at rest and during a Kegel pelvic muscle contraction, after brief standardized verbal instruction. Twenty-three (49%) had an ideal Kegel effort--a significant increase in the force of urethral closure without an appreciable Valsalva effort. Twelve subjects (25%) displayed a Kegel technique that could potentially promote incontinence. Age, parity, weight, estrogen deprivation, prior continence surgery or hysterectomy, and passive urethral function did not predict a successful effort. We concluded that simple verbal or written instruction does not represent adequate preparation for a patient who is about to start a Kegel exercise program. PMID- 1872334 TI - Treatment failure of genital condylomata acuminata in women: role of the male sexual partner. AB - The male sexual partners of women with genital condylomata acuminata are thought to be carriers of human papillomaviruses. It is therefore often recommended that both sexual partners be treated. We studied 360 women with genital warts to test the hypothesis that when the male partners of women with condylomata acuminata are treated, the treatment failure rate decreases. The male sexual partners of 180 of these women were examined and, if indicated, treated (treatment group). The 180 remaining male sexual partners were neither examined nor treated (control group). One hundred twenty-two (68%) men in the treatment group had human papillomavirus-associated lesions. The treatment failure rate of women was 16.7% in the treatment group and 18.9% in the control group. The difference is not statistically significant (p greater than 0.05). The results of this study do not support the hypothesis that the treatment failure rate of women with condylomata acuminata decreases if their male sexual partners are also treated. PMID- 1872335 TI - Partial dissection of the zona pellucida of frozen-thawed human embryos may enhance blastocyst hatching, implantation, and pregnancy rates. AB - The rate of successful implantation after replacement of frozen-thawed embryos in in vitro fertilization is commonly only 5% to 10% per embryo. A limiting factor may be inability of otherwise viable embryos to be released from the intact zonae pellucidae. Culture conditions and/or cryopreservation in in vitro fertilization may affect the zona and impair blastocyst hatching. Therefore opening of the zona by partial slicing by means of micromanipulation before replacement of early cleaved embryos may improve chances of eventual hatching (referred to as assisted hatching). In 65 thawed embryo replacement cycles methyl-prednisolone and antibiotics were given for 4 days mid cycle. Assisted hatching was performed in 32 cycles, with 33 cycles left as controls. Patient's age, infertility, cycle supplementation, and number of thawed and replaced embryos did not differ significantly between the two groups. Rates of viable embryonic implantation were 16% (10/63) and 9% (6/64) in the assisted hatching and control groups, respectively. Group sizes need approximately to double before this trend toward improved implantation with the use of assisted hatching reaches statistical significance. PMID- 1872336 TI - Polycystic ovary syndrome and the androgen-insulin connection. AB - The association of hyperandrogenism, insulin resistance, and polycystic ovarian disease is well established. The accompanying hyperinsulinemia results in acanthosis nigricans, an epiphenomenon of this syndrome. The knowledge that states of insulin resistance of diverse causes are associated with ovarian hyperandrogenism makes the argument for insulin-driven ovarian androgen secretion compelling. However, equally compelling evidence suggests that hyperandrogenism may contribute to insulin resistance and hyperinsulinemia. The irreconcilable differences between these two hypotheses have resulted in an array of contradictory studies. In this article a unified concept of polycystic ovary syndrome and its androgen-insulin connection is proposed. The hypothesis incorporates the role of hyperinsulinemia in the androgen excess observed (and vice versa); the key to this connection is the androgen-dependent change in regional body fat distribution and its metabolic consequence. The pathophysiologic features of polycystic ovary syndrome, which has important clinical sequelae, deserve further consideration. PMID- 1872337 TI - The fetal-pelvic index: a method of identifying fetal-pelvic disproportion in women attempting vaginal birth after previous cesarean delivery. AB - In 1986 the fetal-pelvic index was introduced as an accurate method of prospectively identifying the presence or absence of fetal-pelvic disproportion. The concept of the fetal-pelvic index is one in which the fetal head and abdominal circumferences (ultrasonographic mensuration) are compared with the respective maternal pelvic inlet and midpelvic circumferences (x-ray pelvimetry). The purpose of this study is to evaluate the efficacy of this index as a predictor of fetal-pelvic disproportion in gravid women attempting vaginal birth after previous cesarean delivery. Findings of the fetal-pelvic index are compared with those of two other means of identifying fetal-pelvic disproportion (Colcher Sussman x-ray pelvimetry and ultrasonographically derived estimated fetal weight of greater than or equal to 4000 gm). Of the 65 prospective study participants, 18 (28%) failed to progress in labor, and a repeat cesarean delivery was required. Forty-seven of the 52 patients with a negative fetal-pelvic index value were delivered vaginally (negative predictability = 0.90). Of the five with false negative fetal-pelvic index values, four fetuses persisted in an occipitoposterior position and failed to progress in labor. All 13 patients with a positive fetal-pelvic index value failed to progress in labor and required a cesarean delivery (positive predictability = 1.00). In contrast, when used alone, neither x-ray pelvimetry nor ultrasonography-determined estimated fetal weight of greater than or equal to 4000 gm provided accurate identification of fetal-pelvic disproportion. PMID- 1872338 TI - Acute myocardial infarction associated with prostaglandin E2. AB - Prostaglandin E2 is rarely associated with serious maternal side effects when used for second-trimester pregnancy termination. Acute myocardial infarction complicating therapeutic pregnancy termination with prostaglandin E2 in a patient with chronic glomerulosclerosis and severe hypertension is reported. PMID- 1872339 TI - CA 125 regression: a model for epithelial ovarian cancer response. AB - The rate of decline of CA 125 in effectively treated epithelial ovarian cancer is described by the exponential regression curve CA 125 = EXP [i - s (days after surgery)]. In this equation i, the y-axis intercept, measures initial tumor burden whereas s, the slope of the regression curve, is determined by the extent of cytoreductive surgery and the subsequent response to chemotherapy. Departure from the regression curve uniformly results in progressive disease. In patients whose cancers had been completely removed, we calculated the mean half-life of CA 125 to be 10.4 days (range 4 to 21). In this case s = 0.0835 and characterizes the ideal regression rate. The model predicts that high-dose cisplatin chemotherapy (s = 0.0671) is more effective than low-dose cisplatin (s = 0.0380) (p less than 0.03) in eliminating residual cancer. Because s can be calculated within 2 to 3 months of treatment and then compared with s for the ideal regression curve and with the values of s reported for standard chemotherapy, evaluation of any new treatment protocol can be facilitated with this method. PMID- 1872340 TI - Uterine rupture at term pregnancy with the use of intracervical prostaglandin E2 gel for induction of labor. AB - Prostaglandin E2 is a powerful oxytocic agent that reliably initiates labor, even in the presence of an unripe cervix. The low incidence of fetomaternal complication contributes to its universal use. We report a rare case of uterine rupture after intracervical application of prostaglandin E2 gel. Thus far no prostaglandin compound or method of administration seems to be exempt from such a complication. PMID- 1872341 TI - External cephalic version after previous cesarean section. AB - Approximately 100,000 cesarean sections are performed each year in the United States because of breech presentation. Numerous studies have shown that external cephalic version can eliminate the need for many of these operations. However, because of the fear of uterine rupture, these studies have generally excluded patients who have undergone previous cesarean section. To evaluate the validity of this exclusion policy, we studied patients with one or more previous cesarean sections and breach presentations near term. Version attempts were successful in 82% of 56 patients who had undergone a previous cesarean section. Sixty-five percent of the successful version patients went on to have vaginal birth after cesarean section. There were no serious maternal or fetal complications associated with the version attempts. We conclude that external cephalic version is a reasonable option in patients with prior low transverse cesarean section. PMID- 1872342 TI - One-blade rotation of a persistent posterior vertex. AB - Fifteen women in labor at term with no evidence of protraction or arrest disorder successfully underwent a single-blade rotation of the fetus from occipitoposterior to occipitoanterior position. There were no failures, no fetal injuries, and no significant maternal trauma. This method of forceps rotation appears to be a safe alternative to current methods of managing occipitoposterior positions. PMID- 1872343 TI - Comparative efficacy of clindamycin versus erythromycin in eradication of antenatal Chlamydia trachomatis. AB - Antenatal Chlamydia trachomatis infections are associated with both maternal and neonatal morbidity. Erythromycin, the only drug recommended for treatment during pregnancy, is often poorly tolerated, thus preventing successful cure. We have done a prospective, randomized, double-blind, placebo-controlled trial to compare the efficacy of clindamycin with that of erythromycin base in eradication of antenatal chlamydia. A total of 126 patients with documented cervical infection were enrolled before 24 weeks' gestation to receive clindamycin (450 mg), erythromycin (333 mg), or placebo orally four times daily for 14 days. Partners received doxycycline, 100 mg, twice daily for 7 days. Both clindamycin and erythromycin were effective agents with cure rates of 92.7% and 83.8%, respectively. Erythromycin therapy was associated with significantly more gastrointestinal complaints than was placebo therapy (23.1% (9/39) vs. 2.4% (1/41), p less than 0.02) whereas clindamycin was not. Patients who experienced side effects were more likely to be poorly compliant (p less than 0.03) and patients with moderate-to-good compliance were more likely to be cured than were women who were poorly compliant (p less than 0.002). Results of test of cure cultures performed immediately on completion of therapy did not differ significantly from those taken 4 weeks later. PMID- 1872344 TI - Congenital hydronephrosis: correlation of fetal ultrasonographic findings with infant outcome. AB - Although congenital hydronephrosis is a common fetal disorder, ultrasonographic criteria for prenatal diagnosis remain poorly defined. In this study prenatal ultrasonographic findings were correlated with postnatal outcome in 63 fetuses with suspected hydronephrosis. Prenatal ultrasonographic measurements included length, anteroposterior diameter, and transverse diameter of the kidney and renal pelvis, as well as dorsal renal parenchymal thickness. In 45 of the 63 fetuses, hydronephrosis was confirmed postnatally. These infants were divided into two groups on the basis of renal status: (1) abnormal renal function and/or surgery required (n = 31) and (2) normal renal function with no surgery required (n = 14). The anteroposterior diameter of the renal pelvis was the simplest and most sensitive technique for prenatal diagnosis of congenital hydronephrosis, allowing identification of 100% of cases. Postnatal follow-up studies are warranted if an anteroposterior pelvic diameter is greater than or equal to 4 mm before 33 weeks or greater than or equal to 7 mm after 33 weeks. PMID- 1872345 TI - Endomyocardial ultrastructural findings in preeclampsia. AB - Ultrastructural findings in endomyocardial biopsy specimens obtained during cardiac catheterization in a patient with severe preeclampsia are described. Intramyocardial vessels revealed prominent swelling of the endothelial cell cytoplasm. In addition, cardiac myocyte mitochondria showed swelling and clearing within the matrix. Endomyocardial ultrastructural injury occurs in severe preeclampsia. PMID- 1872346 TI - Psychosocial support for maternal stress during pregnancy: effect on birth weight. AB - In a previous study we showed that moderate to severe stress during pregnancy was inversely related to infant birth weight. Using the same criteria for stress (according to the Social Readjustment Rating Scale of Holmes and Rahe), we studied 86 white mothers with singleton pregnancies and with no known medical or obstetric risk factors for reduced birth weight. After strict randomization, data were analyzed for 43 mothers who received psychosocial support between enrollment at +/- 20 weeks and delivery at +/- 38 weeks and for 43 control mothers who received standard care at the antenatal clinic. In the supported group seven infants weighed less than 3000 gm at birth versus 18 control infants (p = 0.008), and analysis revealed that this effect was more the result of improved intrauterine growth than of prolongation of pregnancy. These findings are of little clinical relevance as far as the neonate is concerned, but they do indicate that psychosocial support has a significant effect on birth weight. It is possible that previous studies that have looked only for an effect on low- or very-low-birth-weight rates might have missed this clinically measurable benefit of counseling. PMID- 1872347 TI - Transvaginal removal of ovaries with endoloop sutures at the time of transvaginal hysterectomy. AB - Twenty patients were evaluated for possible oophorectomy during transvaginal hysterectomy. Of 40 ovaries, nine were removed with a standard clamp technique. Twenty-two ovaries could not be removed by the clamp technique but were successfully removed with endoloop sutures. Safe transvaginal removal was not thought to be possible for the remaining nine ovaries. PMID- 1872348 TI - Improving disclosure of smoking by pregnant women. AB - Smoking is a major modifiable risk factor in pregnancy, and low-cost interventions have been developed and tested in diverse populations of pregnant smokers. Successful intervention depends on identification, however, and nondisclosure can be a problem. This randomized study compared rates of disclosure with two response formats--multiple choice, in which the patient is able to describe herself as having "cut down," and the usual history question, "Do you smoke?," in which she is forced to answer simply "yes" or "no". Each format was tested in both oral and written channels with a multiethnic adult prenatal population (n = 1078) entering care in a multispecialty group. Study results indicate that the multiple choice question improved disclosure, regardless of channel (oral versus written), by 40%. This effect was observed across racial and ethnic groups. Biochemical tests of urine samples from reported nonsmokers indicated smoking in only 3%. Eleven percent of the "nonsmokers" in the experimental groups refused consent for the urine test, however, and many of these were probably smokers. PMID- 1872349 TI - Thrombotic thrombocytopenic purpura first seen as massive vaginal necrosis. AB - Thrombotic thrombocytopenic purpura is a hematologic disorder that affects the microcirculation. A 38-year-old woman was first seen with fever, thrombocytopenia, and vaginal bleeding. Pelvic examination revealed massive vaginal necrosis. Hematology consultation resulted in agreement with the diagnosis of thrombotic thrombocytopenic purpura. This is the first reported case of thrombotic thrombocytopenic purpura first seen as vaginal necrosis of which we are aware. PMID- 1872350 TI - Association of immunoreactive eosinophil major basic protein with placental septa and cysts. AB - A protein that is immunochemically indistinguishable from the major basic protein of the eosinophil granule is present at elevated concentrations in the plasma of pregnant women. Major basic protein has been localized to placental trophoblasts known as X cells. Because X cells are located in placental septa and septal cysts, we tested whether the numbers of these structures are correlated with plasma levels of major basic protein. Data analysis revealed strong positive correlations between maternal plasma major basic protein concentrations and the number of placental septa, septal cysts, and subchorial cysts and the presence of subchorial fibrin deposits. No significant correlation was found between plasma major basic protein levels and other variables examined, such as placental weight. Thus major basic protein is a specific marker for septa and cysts, presumably because it is an X-cell product. The study of major basic protein may aid in delineating the function and ontogeny of X cells, as well as their role in fibrin deposition and in septa and cyst formation. PMID- 1872351 TI - A case report of massive vulvar edema during tocolysis of preterm labor. AB - Bilateral vulvar edema that is not associated with preeclampsia has been reported only rarely during pregnancy or the puerperium. A primiparous patient in premature labor at 34 weeks' gestation with no history of lymphatic or venous obstruction underwent combination tocolysis with intravenous ritodrine and magnesium sulfate. On the fifth day of tocolysis, edema developed in the right labium majus pudendi and gradually spread to the left labia during the ensuing 24 hours. The patient remained afebrile, normotensive, and without signs of localized infection or anasarca. A trial of triple intravenous antibiotics and local skin care proved ineffective. By the ninth hospital day, the edema and discomfort had progressed, thereby precluding vaginal examination without sedation. In spite of progressive cervical dilatation with tocolysis, cesarean delivery was performed. With no further treatment, the vulvar edema gradually resolved during the next week. PMID- 1872352 TI - Uterine activity after preterm premature rupture of the membranes. AB - Preterm premature rupture of the membranes complicates few pregnancies but is a major contributor to overall perinatal morbidity and mortality. Although a reduced incidence of preterm premature rupture of fetal membranes has been reported in women who had antepartum uterine activity monitoring, there are few data regarding uterine activity after preterm premature rupture of fetal membranes. Therefore daily uterine activity monitoring was performed in 101 consecutive women with preterm premature rupture of fetal membranes between 26 and 34 weeks' gestation. The mean gestational ages at rupture and delivery were 31.4 +/- 2.3 and 33.7 +/- 4.5 weeks, respectively. A significant increase in contraction frequency was identified within 24 hours of onset of preterm labor (p less than 0.005). A contraction frequency of four or more per hour predicted the onset of labor within 24 hours with a sensitivity of 72%, a specificity of 90%, a positive predictive value of 54%, and a negative predictive value of 95%. These results indicate that most women with preterm premature rupture of fetal membranes exhibit a baseline contraction frequency that is similar to that of women with intact membranes and premature labor. An abrupt increase in contraction frequency is a warning of impending labor. PMID- 1872353 TI - Acute cutaneous vasculitis associated with prolonged intravenous ritodrine hydrochloride therapy. AB - A patient with twin gestation was hospitalized because of preterm labor and treated with intravenous ritodrine hydrochloride (Yutopar, Astra Pharmaceutical Products, Westborough, Mass.). After greater than 4 weeks of therapy, the patient had a petechial rash and prolonged bleeding time, which were diagnosed and confirmed by skin biopsy at cesarean section as vasculitis. This is the first documented case of vasculitis associated with ritodrine use. PMID- 1872354 TI - The three most common occupational exposures reported by pregnant women: an update. AB - Many uncertainties exist in regard to counseling women with occupational exposures during pregnancy. This is due to limited knowledge of the reproductive toxicologic effects of industrial agents, lack of safety standards aimed at protecting the fetus, and limitations in assessing the extent of exposure. The approach to this subject taken by the Motherisk Program and a review of the three most common occupational exposures are presented. Epidemiologic studies and measurements of radiation do not suggest a reproductive hazard for video display terminals. Exposure to organic solvents is hard to quantitate, and information is sparse and sometimes contradictory, and therapeutic decisions are difficult to reach. To date there is no convincing evidence that working with organic solvents within safety regulations would harm a fetus, in contradistinction to detrimental fetal effects of solvent abuse. The reproductive risks of lead are well documented, fetal exposure can be assessed, and effective treatment exists, but its effects on the pregnancy have not been fully established. However, new evidence suggests that maternal levels that are much lower than the accepted adult limits may be damaging to the fetus. PMID- 1872355 TI - Effects of vibration frequency and tissue thickness on intrauterine sound levels in sheep. AB - Pure-tone sinusoidal mechanical vibratory stimuli ranging in frequency from 4 to 4000 Hz were applied to the ventral abdominal wall of pregnant ewes, and intrauterine sound pressure levels were recorded with a hydrophone 5, 10, 15, and 20 cm from the surface. There were significant decreases in sound pressure levels with increasing frequencies (p less than 0.0001) and increasing depth (p = 0.01). There was no significant interaction between these two variables. An electronic artificial larynx was also activated on the abdominal wall, resulting in quite high sound pressure levels (mean, 119 dB) measured 5 cm from the surface, with a significant decrease in sound pressure levels as the thickness of the intervening maternal tissues increased (p = 0.005). These results suggest that the frequency of vibratory stimulus used and the thickness of the maternal abdominal wall could influence fetal response to the vibroacoustic stimulation test by affecting intrauterine sound pressure levels. PMID- 1872356 TI - The interaction of electrosurgical bipolar forceps and generators on an animal model of fallopian tube sterilization. AB - Electrosurgical tubal sterilization with bipolar forceps has shown a variable and, in certain studies, a high failure rate. Some physicians have questioned if failure rates are due to an incompatibility between bipolar forceps and bipolar generators of different manufacturers. This manuscript presents data on tissue desiccations performed on a rat uterine horn model that uses two bipolar forceps of quite different designs and two popular bipolar generators. The data demonstrate that if an appropriate amount of energy, between 100 and 117 J, is applied to the tissue, consistent destruction occurs, regardless of the generator forceps combination used. Histologic examination of the desiccated uterine horns displayed complete occlusion of all samples 8 weeks after the procedure. However, immediately and at 3 weeks after the procedure patent uterine horns were found. In the patent samples most samples displayed considerable electrosurgical damage. PMID- 1872357 TI - Fetal hypertension induced by norepinephrine infusion and umbilical artery flow velocity waveforms in fetal sheep. AB - This study was designed to examine the effects of fetal hypertension on the umbilical artery pulsatility index. Fetal arterial blood pressure and umbilical venous pressure were measured in eight sheep, 3 to 5 days after surgery. Umbilical blood flow was measured with an electromagnetic flowmeter around the common umbilical vein. Umbilical artery flow velocity waveforms were obtained either by an indwelling 5 MHz pulsed Doppler device (n = 4) or transcutaneously by a 4 MHz continuous-wave Doppler device (n = 4). Fetal blood pressure was raised by intravenous infusion of norepinephrine 10 micrograms/min during 5 minutes. Norepinephrine infusion resulted in elevated arterial and umbilical venous pressures, accompanied by a bradycardia during the first 3 minutes. Umbilical blood flow, calculated placental vascular resistance, and umbilical artery pulsatility index did not change. After atropine administration, the norepinephrine-induced elevated arterial and umbilical venous pressures were accompanied by tachycardia, increased umbilical blood flow, and no change in placental vascular resistance and umbilical artery pulsatility index. It is concluded that fetal arterial hypertension provoked by norepinephrine infusion has no effect on placental vascular resistance, umbilical blood flow, and umbilical artery pulsatility index. PMID- 1872358 TI - Inhibition of oxytocin-induced uterine contractions by an oxytocin antagonist in the pregnant baboon. AB - Uterine contractions were induced with oxytocin in anesthetized pregnant baboons (Papio anubis) at three stages of pregnancy (days 140, 156, and 169; normal gestation length, 184 days). After the contractile activity was greater than two to three contractions every 10 minutes, beta-mercapto-beta, beta cyclopentamethylenepropionic acid1-[D-Trp2,Phe3,Ile4,Arg8]-oxytocin, a novel oxytocin antagonist produced in our laboratories, was given simultaneously with the oxytocin for 90 minutes. Contractile force (frequency x mean amplitude) was determined for 30 minutes before and for three 30-minute intervals after the oxytocin antagonist was administered. Animals at 140 days' gestation showed a significant (p less than 0.05) decrease in contractile force in the first 30 minute interval after oxytocin antagonist infusion was initiated, whereas those at days 156 and 169 showed decreases (p less than 0.05) at the second 30-minute interval. In addition, in late gestation a higher dose of oxytocin antagonist per unit of oxytocin was required to prevent uterine contractions. In conclusion, these results suggest (1) that an oxytocin antagonist can inhibit oxytocin induced uterine contractions in the pregnant baboon and (2) that the interval from oxytocin antagonist administration to significant inhibition of uterine contractions appears to increase with advancing gestational age. PMID- 1872359 TI - Prediction of survival of infants weighing less than 800 grams at birth: errors in the application of multivariate statistical techniques. PMID- 1872360 TI - A plea for early diagnosis of fallopian tube carcinoma: can hysteroscopy be of use? PMID- 1872361 TI - Egg transport through the oviduct. PMID- 1872362 TI - Breast disease management in an obstetrics and gynecology department. PMID- 1872363 TI - Untreated luteal phase deficiency as another possible risk factor for preterm delivery. PMID- 1872364 TI - Relationship between central venous pressure and pulmonary capillary wedge pressure in severely toxemic patients. PMID- 1872365 TI - Pregnancy and Wilson's disease. PMID- 1872366 TI - Cellular mechanisms of fatigue in skeletal muscle. AB - Prolonged activation of skeletal muscle leads to a decline of force production known as fatigue. In this review we outline the ionic and metabolic changes that occur in muscle during prolonged activity and focus on how these changes might lead to reduced force. We discuss two distinct types of fatigue: fatigue due to continuous high-frequency stimulation and fatigue due to repeated tetanic stimulation. The causes of force decline are considered under three categories: 1) reduced Ca2+ release from the sarcoplasmic reticulum, 2) reduced myofibrillar Ca2+ sensitivity, and 3) reduced maximum Ca(2+)-activated tension. Reduced Ca2+ release can be due to impaired action potential propagation in the T tubules, and this is a principal cause of the tension decline with continuous tetanic stimulation. Another type of failing Ca2+ release, which is homogeneous across the fibers, is prominent with repeated tetanic stimulation; the underlying mechanisms of this reduction are not fully understood, although several possibilities emerge. Changes in intracellular metabolites, particularly increased concentration of Pi and reduced pH, lead to reduced Ca2+ sensitivity and reduced maximum tension, which make an important contribution to the force decline, especially with repeated tetanic stimulation. PMID- 1872367 TI - Inositol phosphates and [Ca2+]i signals in a differentiating exocrine cell. AB - Generation of inositol phosphates and changes in intracellular Ca2+ concentration [( Ca2+]i) upon muscarinic receptor activation were studied in isolated cells from the nasal salt gland of Anas platyrhynchos, comparing responses in the poorly differentiated cells from ducks drinking only tap water (naive cells) with the more fully differentiated actively secreting cells from ducks drinking 1% NaCl solution for 48 h before the experiment (stressed cells). On stimulation, naive cells showed a rapid five- to sevenfold increase in inositol 1,4,5 trisphosphate [Ins(1,4,5)P3], accompanied by similar changes in Ins(1,3,4,5)P4, whereas both values increased only twofold in stressed cells. [3H]quinuclidinyl benzilate binding experiments revealed that these differences in inositol phosphate production were correlated with differences in the numbers of muscarinic acetylcholine receptors. Continuous recordings of [Ca2+]i revealed that Ca2+ release from intracellular stores upon stimulation was similar in both cell types, but the sustained [Ca2+]i signal (dependent on Ca2+ entry) was three times more pronounced in stressed cells. The results suggest that the adaptive differentiation of salt gland cells is associated with the increased expression of the receptor-mediated Ca2+ entry mechanism. In addition, the high rate of phosphoinositide hydrolysis in naive cells upon receptor activation may have a significance in cell growth, proliferation, and differentiation, which are elements of the development of the salt transport capabilities in these cells. PMID- 1872368 TI - Blockade by lithium ions of potassium channels in rat anterior pituitary cells. AB - Extracellular Li+ has been known to facilitate the basal secretion of growth hormone from anterior pituitary cells and of catecholamine from chromaffin cells. In both cases, the intracellular accumulation of Li+ seems to be the prerequisite, and the presence of extracellular Ca2+ is indispensable. In this series of experiments, we examined whether Li+ blocked K+ currents by using primary cultured anterior pituitary cells from male rats. K+ currents were measured in the whole cell configuration of the patch-clamp technique. Extracellular Li+ (140 mM) suppressed both the delayed rectifier K+ current (IK) and the transient outward K+ current to 71 and 69% of control, respectively, in a reversible manner. IK elicited by a voltage step to +70 mV from holding potential of -70 mV was suppressed by 32.5 mM internal Li+ to 28% of control. Half-maximal suppression of K+ conductance by internal Li+ was 16 mM. Furthermore, Ca(2+) channel blocker methoxyverapamil potently suppressed Li(+)-induced growth hormone secretion. From these results we propose that the blockade by Li+ of K+ channels could depolarize the cells and activate Ca2+ channels, thereby promoting the influx of Ca2+ and hormone secretion as a mechanism of Li(+)-induced hormone secretion. PMID- 1872369 TI - Altered binding site for Ca2+ in the ryanodine receptor of human malignant hyperthermia. AB - The binding properties of [3H]ryanodine, a specific ligand of the receptor complex that forms the Ca2+ release channel of sarcoplasmic reticulum, were studied in normal (N) and malignant hyperthermia-susceptible (MH) human skeletal muscle. Integrity of the solubilized ryanodine receptor was demonstrated by single-channel recordings in planar bilayers and by the changes produced by activators and inhibitors of the Ca2+ release channel on the binding properties of [3H]ryanodine. N and MH receptors were capable of binding [3H]ryanodine in a Ca(2+)-dependent manner. Scatchard analysis showed that a single binding site for [3H]ryanodine was present in either N or MH muscle. Binding affinity was approximately the same in N and MH (Kd approximately 7 nM), when the Ca2+ concentration was greater than 30 microM. At 0.3 microM Ca2+, MH receptors displayed a higher affinity for [3H]ryanodine (Kd = 4.1 +/- 1.0 nM) than N receptors (Kd = 7.1 +/- 0.8 nM). The presence of a single Kd for [3H]ryanodine in MH muscle, distinct from that of N muscle, indicated that MH muscle does not have detectable levels of N receptors. Ca2+ dependence of [3H]ryanodine binding further suggested that MH receptors had a higher affinity for Ca2+ (Kd[Ca2+] = 120 +/- 50 nM) than N receptors (Kd[Ca2+] = 250 +/- 80 nM). Caffeine increased [3H]ryanodine binding at submicromolar [Ca2+], and the effect was larger in MH. Apparent affinity constants for caffeine were 13 +/- 1.8 mM in N and 6 +/- 0.8 mM in MH receptors. Evidently, the ryanodine receptor of MH-susceptible human skeletal muscle has an unusually high sensitivity to Ca2+ which is augmented by caffeine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872370 TI - Change of Ca2+ requirement for myosin phosphorylation by prostaglandin F2 alpha. AB - The mechanism of contraction of vascular smooth muscle by prostaglandin F2 alpha (PGF2 alpha) was examined by simultaneous measurement of the intracellular Ca2+ concentration [( Ca2+]i), force, and myosin light-chain (MLC) phosphorylation in ferret aorta. In the presence of 2.5 mM extracellular Ca2+, PGF2 alpha (10(-5)M) produced a tonic contraction with a transient spike in [Ca2+]i, followed by a relatively small sustained increase in [Ca2+]i (from a basal level of 2.32 +/- 0.07 x 10(-7) to 2.72 +/- 0.05 x 10(-7) M). In Ca(2+)-free bathing media, PGF2 alpha also produced a tonic contraction with a small spike in [Ca2+]i, indicating a release of Ca2+ from intracellular store sites, followed by no significant increase in [Ca2+]i. Ca(2+)-force curves were constructed by plotting the calibrated steady-state aequorin light signal against the resulting steady-state force. The curve was significantly shifted to the left by PGF2 alpha. PGF2 alpha also shifted the Ca(2+)-phosphorylation curve to the left. These results suggest that PGF2 alpha causes contraction by both elevating [Ca2+]i and decreasing the Ca2+ requirement for MLC phosphorylation. The data are consistent with a mechanism where there is either an increase in activity of MLC kinase or a decrease in phosphatase activity. Additionally, there was a smaller, but statistically significant, effect to increase force at any one phosphorylation level, pointing to the possibility of regulation of contractile force separate from MLC phosphorylation. PMID- 1872371 TI - Correlates of fatigue resistance in canine skeletal muscle stimulated electrically for up to one year. AB - In response to patterns of chronic electrical stimulation that increase its overall level of use, mammalian skeletal muscle becomes highly resistant to fatigue. The metabolic basis for this adaptation is well documented in the rabbit, but up to now it has not been possible to identify analogous changes in the dog. In this study, canine latissimus dorsi muscles were stimulated in situ for 2, 6 and 12 mo. Marked increases in fatigue resistance were consistently demonstrated. Citrate synthase and succinic dehydrogenase, conventionally used as markers of oxidative metabolism, did not increase in activity, but enzymes involved in major pathways supplying substrates to the tricarboxylic acid cycle increased up to threefold. Stimulation elevated the volume fraction of mitochondria 1.5-fold and that of lipid droplets 4.5-fold. After 6 mo of stimulation, mean fiber diameter had decreased by 30% and the area occupied by nonmuscle tissue had increased by 11%; these changes showed no further progression at 12 mo. Thus stimulated muscle becomes stably adapted to an increase in use, but the metabolic strategies for achieving increased fatigue resistance vary between species. PMID- 1872372 TI - Inhibition of glycogenesis in rat muscles partially depleted of glycogen. AB - This study aimed to examine the extent to which repletion of glycogen in muscles partially depleted of glycogen may be inhibited by contractions and epinephrine. Four experiments were carried out on untrained male Wistar rats. 1) Animals ran 150 min (1,200 m/h) on a treadmill set at +10 degrees incline. After 60, 90, and 120 min of running, they were given glucose (40% solution, 1 ml/100 g) by a stomach tube. 2) Rats ran on a treadmill set as above for 20 min at 3,200 m/h and then 2 h at 800 m/h. 3) In anesthetized rats, gastrocnemius-plantaris muscle group was made to contract isometrically by means of stimulation of the sciatic nerve. The nerve was stimulated with tetanic pulses (7 V, 0.05-ms duration, delivered in 100-ms trains at 100 Hz): first 15 min, 2 pulses/s, then 2 h, 1 pulse/2 s. 4) Epinephrine (0.5 mg/kg) was administered subcutaneously 10 min before onset of stimulation of the sciatic nerve. The nerve was stimulated 15 min with tetanic pulses (as above), 2 pulses/s. Next, rats were rested for 2 h. Level of glycogen was determined in samples of white and red gastrocnemius, plantaris, and soleus. Initial running or stimulation resulted in pronounced glycogen depletion in each muscle. Thereafter, either considerable or full repletion of glycogen occurred in the muscles despite continued contractile activity or the presence of epinephrine. The degree of repletion depended both on the type of muscle and the type of activation of glycogenolysis (running, stimulation of the nerve, epinephrine).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872373 TI - Divalent cations modulate the transient outward current in rat ventricular myocytes. AB - The modulation of the transient outward K+ current (Ito) by divalent cations was studied in enzymatically isolated rat ventricular myocytes with the whole cell patch-clamp technique. At holding potentials negative to -70 mV, 1 mM Cd2+ suppressed Ito, whereas, at potentials positive to -50 mV, the current was augmented. These effects were caused by shifts in the voltage dependence of both activation and inactivation of Ito toward more positive potentials. Cd2+ also slowed the activation kinetics of Ito by shifting the voltage dependence of its rate of activation, but the rate of inactivation was unaffected. Other divalent cations produced similar shifts but at markedly different concentrations. Thus, in the millimolar range, a rightward shift of approximately 20 mV was produced by 3 Co2+, 5 Ni2+, and 10 Ca2+, whereas 10 microM concentrations of Cu2+ and Zn2+ produced equivalent shifts. Similar effects were seen in hippocampal neurons with micromolar concentrations of Zn2+. Thus divalent cations have marked and specific effects on the kinetics and voltage dependence of Ito and may serve as a regulatory mechanism in its activation, particularly in cells with resting potentials positive to -60 mV. PMID- 1872374 TI - Sodium transport and intracellular sodium activity in cultured human nasal epithelium. AB - Human airway epithelia are predominantly Na(+)-absorbing epithelia. To investigate the mechanisms for Na+ absorption across airway epithelia, the driving forces and paths for Na+ translocation across each membrane were examined with double-barreled Na(+)-selective microelectrodes in cultured human nasal epithelium (HNE). Under control conditions, intracellular Na+ activity (acNa) was 23 +/- 1 mM (n = 44 preparations, 393 impalements). Amiloride (10(-4) M) hyperpolarized the apical membrane and increased the fractional apical membrane resistance but did not affect acNa. Exposure to Na(+)-free luminal solution induced bioelectric responses similar to amiloride but also reduced acNa to 8 +/- 1 mM. Reduction of luminal Na+ concentration ([Na+]) in the presence of amiloride also reduced acNa without further changes in bioelectric parameters. Reduction of serosal [Na+] decreased aNac, a response blocked by bumetanide (10(-4) M). Ouabain (10(-4) M, serosal) led to a reduction in equivalent short-circuit current (Ieq) and increase in acNa. We conclude that 1) acNa is higher in HNE than in most mammalian epithelial cells, 2) the apical membrane expresses a conductive Na+ path, and 3) the basolateral membrane transports Na+ via the Na(+) K(+)-adenosinetriphosphatase and a Na(+)-K(+)-2Cl- cotransport system. PMID- 1872375 TI - Transcellular sodium transport in cultured cystic fibrosis human nasal epithelium. AB - Cystic fibrosis (CF) airway epithelia exhibit raised transepithelial Na+ transport rates, as determined by open-circuit isotope fluxes and estimates of the amiloride-sensitive equivalent short-circuit current (Ieq). To study the contribution of apical and basolateral membrane paths to raised Na+ transport in CF, CF nasal epithelial cultures were studied with double-barreled Na(+) selective microelectrodes and the Ussing chamber technique. Intracellular Na+ activity (acNa) was 24.1 +/- 1.5 mM (n = 36), a value similar to acNa of normal nasal epithelial cells. Reduction of luminal [Na+] to 3 mM abolished Ieq and reduced acNa. Amiloride (10(-4) M) abolished Ieq but increased acNa from 20 +/- 2 to 36 +/- 7 mM (n = 10). Amiloride-induced increase in acNa was not affected by serosal [Na+] reduction but was blocked by preexposure to reduced luminal [Na+]. Amphotericin B increased Ieq during amiloride exposure, indicating that amiloride did not inhibit NA(+)-K(+)-ATPase. Ouabain abolished Ieq and slowly raised acNa. Reduction of serosal [Na+] led to a decrease in acNa that was blocked by bumetanide. It is concluded that 1) CF airway epithelia exhibit an increased apical membrane Na+ permeability, 2) acNa is regulated to a normal level in CF cells despite increased transcellular Na+ fluxes, 3) the abnormal increase in acNa in response to amiloride is dependent on luminal Na+, 4) Na+ is transported across the basolateral membrane by a bumetanide-sensitive cotransport mechanism, and 5) ouabain inhibits the basolateral Na(+)-K(+)-ATPase, causing slow dissipation of the chemical and electrical gradients across the cell membranes. PMID- 1872376 TI - Viscoelastic properties of the contracting detrusor. I. Theoretical basis. AB - This paper presents the theoretical basis for estimating the detrusor's viscoelastic properties using the small-amplitude oscillatory perturbations technique. Three possible configurations of the simplest second-order lumped parameter model of the bladder were analyzed to derive equations of the parameters incremental resistance (R) and incremental elastance (K) in terms of the experimentally measurable magnitude and phase of hydrodynamic stiffness. In model I, single viscous, elastic, and inertial elements were assumed to to be connected in series. In model III the elastic and viscous elements were connected in series, but the inertial element was connected in parallel. With the assumption of a spherical geometry of the bladder, equations were also derived to obtain the bladder wall mechanical properties, spring incremental constant (S), and muscle incremental viscosity (b) as functions of bladder volume and the hydrodynamic properties R and K. Integration of the incremental equation describing the viscous component yields an expression that fits well the force velocity experimental data from bladder strips reported by others. This finding suggests that muscle viscosity measured with the small-amplitude oscillations and analyzed with the proper theoretical model may be related to the force-velocity characteristics of the muscle. The equations delivered here form the basis for analyzing the experimental data described in the companion paper. PMID- 1872377 TI - Viscoelastic properties of the contracting detrusor. II. Experimental approach. AB - Mechanical properties of detrusor muscle were studied with small-amplitude oscillatory volume perturbations in isometrically contracting bladders of anesthetized dogs. Contractions were studied at oscillatory frequencies (f) of 2 and 4 Hz and at bladder volumes (Vbl) ranging from 30 to 110 ml. The magnitude of bladder hydrodynamic stiffness (magnitude of G) increased linearly with mean detrusor pressure (Pdet) while the phase angle remained relatively constant during contraction. The slope (mG) of magnitude of G-Pdet relations had a positive dependence on f and a negative dependence on Vbl. Analysis of oscillatory data, described in the companion paper, was performed using incremental lumped-parameter models consisting of a spring with incremental constant (S = dF/dL), a viscous element with incremental viscosity (b = dF/du), and a mass (m). Only the model where elastic and viscous elements were placed in series with each other and in parallel with mass was compatible with the experimental data. Both S and b increased linearly with effective force (F), defined as Pdet times the cross-sectional area of the intravesical cavity. Slopes of the S-F and b-F relationships (ms and mb) were independent of Vbl and varied only slightly with f. The importance of this finding stems from recognizing that ms and mb correspond to the exponential coefficients of nonlinear series elastic and internal viscosity elements. These parameters, when normalized by resting muscle length, represent fundamental muscle properties independent of muscle cross-sectional area, stretch, or level of activation and compare well with parameters derived from other muscle systems using techniques such as quick releases and isotonic contractions. PMID- 1872378 TI - Constrained optimization and protein structure determination. AB - Energy minimization is one of the main approaches to the computational determination of macromolecular structure. Due to the approximations in the empirical free-energy functions and due to the computational difficulties in locating their global minima, the problem is at present intractable when the only information available is the sequence of subunits forming the molecule. A less demanding problem in terms of both physics and mathematics is constrained optimization, which uses additional but incomplete experimental information such as distances between certain atoms. This paper reviews methods for generating molecular structure using bond lengths and angles as variables and shows how the structure can be fully specified in terms of local geometry. The analysis permits precise statements to be made about the minimum set of distances that specify a unique structure without recourse to energy minimization. We then discuss the complementary situation, i.e., structure prediction with energy minimization based only on sequence information. Finally, we show how distance constraints can be incorporated into energy minimization methods. PMID- 1872379 TI - Loss of abdominal fat and metabolic response to exercise training in obese women. AB - Numerous studies have shown that a high accumulation of abdominal fat is associated with metabolic complications and with an increased risk of coronary heart disease. The present study examined the effects of changes in body fatness and in the level of abdominal fat on metabolic variables in a sample of 13 obese premenopausal women, aged 38.8 +/- 5.3 (SD) yr. Women exercised for 90 min at approximately 55% of maximal aerobic power (VO2 max) four to five times a week for a period of 14 mo. The training program induced a significant increase in VO2 max and a mean reduction in body fat mass of 4.6 kg (P less than 0.01), with no change in fat-free mass. Measurement of adipose tissue areas by computed tomography indicated a greater loss of abdominal fat compared with midthigh adipose tissue (P less than 0.05). The training program also produced significant reductions in the insulinogenic index measured during an oral glucose tolerance test and in plasma cholesterol (Chol), low-density lipoprotein (LDL)-Chol, and apolipoprotein (apo) B levels (P less than 0.05). Training also significantly increased plasma high-density lipoprotein (HDL)-apo A-I and HDL2-Chol levels and decreased plasma HDL3-Chol concentration (P less than 0.05). Whereas no change in postheparin plasma lipoprotein lipase activity was noted, a significant decrease in postheparin plasma hepatic triglyceride lipase activity was observed after training (P less than 0.005). Metabolic responses were not correlated with changes in VO2 max but were significantly correlated with the reduction in body fat mass and/or with the loss of deep abdominal fat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872380 TI - Influence of fatty acids on ammonia and amino acid flux from active human muscle. AB - This study examined the dynamics of ammonia and amino acid exchange of human muscle during prolonged steady-state one-legged exercise at 80% of knee extensor maximal work capacity. Subjects (n = 10) performed leg extensor exercise for 1 h (control series), rested for 40 min while an infusion of Intralipid and heparin was begun, and then exercised the contralateral leg with the identical protocol [free fatty acid (FFA) series]. In the control series, ammonia efflux rose progressively, and 4.4 +/- 0.6 mmol were released in 1 h compared with 2.4 +/- 0.5 mmol (P less than 0.05) in the FFA series. The exercise was associated with large effluxes of total amino acids from the active muscle over the hour (12.8 +/ 4.3 and 10.3 +/- 3.3 mmol for control and FFA, respectively). Glutamine and alanine accounted for 47 and 64% of the efflux for the control and FFA series, respectively, while comparable values for essential amino acids were 24 and 20%. The latter implies that a net muscle protein catabolism was occurring during the exercise. The FFA treatment was associated not only with a reduced muscle ammonia release but also with a decreased (P less than 0.05) arterial concentration of nine amino acids (alanine, methionine, lysine, hydroxyproline, serine, glycine, proline, asparagine, and ornithine). Interpretation is limited due to the treatment order effect, but these data are compatible with the hypothesis that plasma clearance was affected by FFA. PMID- 1872381 TI - Chemical and elemental analysis of humans in vivo using improved body composition models. AB - Six chemical compartments [water, protein, mineral (osseus and cellular), glycogen, and fat] consisting of 11 elements (N, C, Ca, Na, Cl, K, H, P, O, S, and Mg) comprise greater than or equal to 99% of body weight in living humans. The combination of three neutron-activation systems, whole body 40K counting, and 3H2O dilution at Brookhaven National Laboratory now potentially makes it possible to quantify greater than or equal to 96% of the chemical and elemental determinants of body weight in vivo. The aims of the present study were 1) to develop 6- and 11-compartment chemical and elemental models, respectively, and 2) to evaluate these models in a group of 20 healthy adults. Results demonstrated that body weight estimated from either chemical or elemental components was highly correlated with (both r = 0.97, P less than 0.001) and on average differed by less than 4% from actual body weight. The compartmental results obtained using the chemical model were also evaluated by comparing calculated and actual body density (Db) estimated by underwater weighing. Calculated Db [1.041 +/- 0.017 (SD) g/ml] agreed closely and was highly correlated with actual Db (1.039 +/- 0.018 g/ml; r = 0.82; P less than 0.001). Hence a near-complete chemical and elemental analysis of living human subjects is now possible and, with potential future refinements, represents an important opportunity to quantify the effects of gender, aging, and ethnic status on body composition. PMID- 1872382 TI - Relative expansion of extracellular fluid in obese vs. nonobese women. AB - There is a conflict in previous studies with regard to the relation between adipose tissue mass and total body fluid distribution. This study tested the hypothesis that obesity is accompanied by an increase in the extracellular-to intracellular fluid ratio above that observed in nonobese subjects. Extracellular fluid was evaluated in obese (n = 39) and nonobese (n = 26) healthy women, using two different dilution volumes, 35SO4 [extracellular water (ECW)] and 24NaCl [exchangeable sodium (Nae)]. Intracellular water (ICW = 3H2O dilution volume-ECW) and total body potassium (TBK; 40K whole body counting) were assumed to represent intracellular fluid. Two independent markers of relative fluid distribution were formulated as ECW/ICW and Nae/TBK. Obese and nonobese women were of similar age and height but differed in body weight and TBW by 67.7 kg and 12.9 liters, respectively. The obese women had significantly larger absolute ECW, Nae, ICW, and TBK compared with the nonobese women (all P less than 0.001). The ratios ECW/ICW and Nae/TBK were significantly higher in obese vs. nonobese women and were highly correlated with each other (r = 0.54, P less than 0.001) in the pooled group of subjects. Fluid volumes are thus increased in obese women, and the expansion is relatively greater for the extracellular compartment. These results have implications in the study of human body composition and may also account in part for the fluid-overload states that often accompany severe obesity. PMID- 1872383 TI - Hormonal, metabolic, and cardiovascular responses to static exercise in humans: influence of epidural anesthesia. AB - To determine the role of reflex neural mechanisms for hormonal, metabolic, heart rate (HR), and blood pressure (MABP) changes during static exercise, seven health young males performed 10-min periods of two-legged static knee extension both during control and during epidural anesthesia. Comparisons were made at identical absolute (29 Nm) and relative [15% maximal voluntary contraction (MVC)] force. Afferent nerve blockade was verified by hypesthesia below T10-T12 and attenuated postexercise ischemic pressor response. Leg strength was reduced to 67 +/- 5% of control. At same relative force, increases in MABP and HR occurred more rapidly without than with epidural anesthesia (P less than 0.05). This difference was diminished during identical absolute force. Changes in plasma concentrations of catecholamines followed the pattern of HR and MABP responses, with differences between epidural and control experiments being most pronounced early in the work period. Plasma beta-endorphin was elevated only after control exercise. No response at 15% MVC was found for growth hormone, adrenocorticotropic hormone, insulin, glucagon, cortisol, glycerol, free fatty acids, or glucose (P greater than 0.05). In conclusion, during static exercise with large muscle groups and moderate relative force, modest changes in plasma hormones and metabolites take place. Furthermore, afferent nervous feedback from contracting muscles is important in regulation of blood pressure, heart rate, and catecholamine responses during static exercise in humans. PMID- 1872384 TI - In vivo effects of flavonoid EMD 21388 on thyroid hormone secretion and metabolism in rats. AB - In vitro, the synthetic flavonoid EMD 21388 appears to be a potent inhibitor of thyroxine (T4) 5'-deiodinase and diminishes binding of T4 to transthyretin. In this study, in vivo effects of long-term administration of EMD 21388 on thyroid hormone production and metabolism were investigated. Intact male rats received EMD 21388 (20 mumol.kg body wt-1.rat-1.day-1) for 14 days. [125I]T4 and 3,5,3' [131I]triiodotyronine (T3) were infused continuously and intravenously in a double-isotope protocol for the last 10 and 7 days, respectively. EMD 21388 decreased plasma thyroid hormone concentrations, but thyrotropin levels in plasma and pituitary did not change. Plasma clearance rates for T4 and T3 increased. Thyroidal T4 secretion was diminished, but T3 secretion was elevated. Extrathyroidal T3 production by 5'-deiodination was lower. T4 concentrations were markedly lower in all tissues investigated. Total tissue T3 was lower in brown adipose tissue, brain, cerebellum, and pituitary, tissues that express the type II 5'-deiodinase isozyme due to decreased local T3 production. Most tissues showed increased tissue/plasma ratios for T4 and T3. These results indicate that this flavonoid diminished T4 and increased T3 secretion by the thyroid, probably in analogy with other natural flavonoids, by interference with one or several steps between iodide uptake, organification, and hormone synthesis. PMID- 1872385 TI - Endurance training increases metabolic rate and norepinephrine appearance rate in older individuals. AB - We examined the effects of an 8-wk endurance training program (cycling exercise) on resting metabolic rate (RMR) and norepinephrine (NE) kinetics in 19 older persons (64 +/- 1.6 yr). Before and after training, RMR, NE kinetics, maximal O2 consumption (VO2max), body composition, supine blood pressure, estimated energy intake, and fasting levels of glucose, insulin, and thyroid hormones were measured. RMR increased 10% after training. Resting concentrations of NE increased 24% after training due to a 21% increase in NE appearance rate and no change in NE clearance. Training increased VO2max (14%; P less than 0.01) and energy intake (12%; P less than 0.01), whereas no change was noted in body composition. Supine blood pressure and plasma glucose were lower after training, whereas no change was noted in fasting levels of plasma insulin. The increase in RMR was associated with a higher rate of NE appearance (r = 0.57; P = 0.05) and with increase in energy intake (r = 0.56; P = 0.05). Together these two factors accounted for 49% (r2) of the variation of the change in RMR. Changes in blood pressure were not associated with changes in NE kinetics. We conclude that endurance training increases total energy expenditure in older individuals by the direct energy cost of physical activity and by elevating RMR. This increase is partially mediated by an increased NE appearance rate and increased food intake in healthy older individuals. PMID- 1872386 TI - Weight reduction increases adipose but decreases cardiac LPL in reduced-obese Zucker rats. AB - Lipoprotein lipase (LPL) activity and mRNA levels were measured in cardiac muscle and adipose tissue from lean, obese, and weight-stable reduced-obese Zucker rats, both fasted and 2 h after feeding. Fasting epididymal fat LPL activity was substantially higher in obese rats relative to lean rats [6.9 vs. 0.2 nmol free fatty acid (FFA).10(6) cells-1.min-1; P = 0.0001], and was higher still in reduced-obese rats (15.7 nmol FFA.10(6) cells-1.min-1; P = 0.002). Adipose tissue LPL increased with feeding in all three groups. In marked contrast, fasting cardiac muscle LPL was lower in obese rats relative to lean (28.8 vs. 38.5 nmol FFA.g-1.min-1; P = 0.0064) and was lower still in reduced-obese rats (14.5 nmol FFA.g-1.min-1; P = 0.0001). LPL mRNA levels increased in adipose tissue along with enzyme activity; however, the magnitude of the changes were relatively small, suggesting that the primary regulatory steps are posttranslational. Weight reduction studies were also carried out in Sprague-Dawley rats with similar results. These studies show that sustained weight reduction results in coordinate changes in tissue-specific LPL, favoring delivery of lipoprotein triglyceride fatty acids to adipose tissue relative to cardiac muscle and the restoration of energy stores. PMID- 1872387 TI - Postnatal changes in lambs of two pathways for thyroxine 5'-monodeiodination in brown adipose tissue. AB - We have recently shown that ovine fetal brown adipose tissue (BAT) contains two distinct iodothyronine 5'-monodeiodinase (5'MDI) activities, one with a high Km (type I) and another with a low Km (type II). Both activities increased to maximum levels near term (150 days gestation). BAT plays a major role in neonatal temperature regulation in lambs, and available evidence suggests that BAT 5'MDI activity is closely linked to thermogenic capacity. To better characterize the changes in 5'MDI after birth, we studied both type I and type II 5'MDI in lamb BAT from the time of birth to 30 days of postnatal age. Type I 5'MDI activity [pmol 3,5,3'-triiodothyronine (T3).mg protein-1.h-1] showed no significant changes during the first 11 days after birth [newborn (NB), 95 +/- 16; 1 day, 83 +/- 20; 3-4 days, 80 +/- 11; 10-11 days, 92 +/- 28]. Activity decreased significantly at 30 days (24 +/- 8.9, P less than 0.05). On the other hand, the type II 5'MDI activity (fmol I- released.mg protein-1.h-1) increased significantly (P less than 0.01) during the first 4 days, (NB, 348 +/- 23; 1 day, 679 +/- 37; 3-4 days, 785 +/- 199), decreased toward NB values (401 +/- 87) at 10 11 days of age, and fell to 66 +/- 31 at 30 days (P less than 0.05 vs. NB). Kinetic analysis of BAT type II thyroxine 5'MDI revealed a rise in maximum velocity from NB to 1 and 3-4 days of age without a change in the enzymatic activity Km.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872388 TI - Homologous amino-terminal radioimmunoassay for rat parathyroid hormone. AB - Existing radioimmunoassays for parathyroid hormone (PTH) in rat plasma are based on cross-reactivity of rat PTH (rPTH) with heterologous antisera. We used the synthetic NH2-terminal fragment of rPTH [rPTH-(1-34)] to develop a homologous radioimmunoassay for circulating PTH. An antiserum to rPTH-(1-34) was raised in a goat (G-813), and the same peptide was used as radioligand (125I) and standard. Purification of the label by high-performance liquid chromatography (HPLC) increased specific binding greater than twofold and sensitivity by 50-100%. With a final antiserum dilution of 1:70,000, maximum specific binding of 30-33%, nonspecific binding of 1-5%, and 50-microliters sample additions, the assay detection limit was 1.8-2.5 pmol/l. A midregional fragment of human PTH did not displace 125I-labeled rPTH-(1-34). HPLC of extracts of rat parathyroid glands and hyperparathyroid plasma showed only a single peak of immunoreactivity that eluted 2 min after rPTH-(1-34). Dose dilution curves for rat parathyroid gland extracts, rPTH-(1-34) added to rat plasma, and endogenous rat plasma PTH all paralleled the standard curve. Immunoreactive PTH (irPTH) was detectable in greater than 90% of fasting normal rat plasma and changed appropriately in response to hyper- and hypocalcemia induced by low-calcium and vitamin D-deficient diets, injections of calcium and EDTA, and after thyroparathyroidectomy. The normal range for rat plasma irPTH was less than 2.0-12 pmol/l, in general agreement with bioassay results of others. Thus rPTH-(1-34) is an excellent immunogen for raising antisera to rPTH, and assays incorporating it may be of great value in studying rat parathyroid physiology. PMID- 1872389 TI - Cut set analysis of compartmental models with applications to experiment design. AB - Conventional compartmental analysis typically involves equations derived from mass-rate balance considerations for each compartment (pool), with each equation associated with a single pool. However, alternative mathematical descriptions, which effectively group pools into various other configurations, facilitate model analysis in certain applications, e.g., for kinetic experiment design or analysis. Such equivalent models are usually obtained using (often) complex matrix operations. An alternative approach, cut set analysis, can be applied directly to the graph of the compartmental model to readily generate alternative mathematical descriptions in which the needed equivalence transformations are easily performed graphically. This graphical transformation is developed here for linear, time-invariant multicompartmental models in which particular parameter values are the experimental objective. The method potentially provides greater flexibility in analyzing complex compartmental models in theory and practice, and it is exemplified here by application to the design of steady-state kinetic endocrine system studies in experimental animals. PMID- 1872390 TI - Estimation of fructose 6-phosphate-fructose 1,6-bisphosphate cycling in liver and fate of 3H of [6-3H]glucose. PMID- 1872391 TI - Can regulatory peptides be regarded as words of a biological language. AB - Despite the complexities of individual systems, neurocrine, endocrine, and growth factor-mediated signaling systems show striking similarities in the molecules they use for communication and in their signal-transduction mechanisms. In contrast to the traditional view in cell biology, which has focused on the regulatory aspects of neurocrine and endocrine messengers and growth factors, an analysis of various aspects of peptidergic cell-to-cell communication on the basis of information theory is suggested. According to theorems for efficient and error-free encoding, the differences in rate and distance of information transfer and in noise interference between neurocrine, endocrine, and growth factor mediated messages require different encoding strategies. These differences are reflected in the use of plurichemical transmission (to increase information content) or in the number and sequence of amino acids within peptide molecules (to protect against noise interference). In contrast to the quantitative information content, the qualitative information of the messages is not transmitted but is retrieved when the message interacts with transduction networks at the receiver cell. The semantic information is contained within the rules specifying the conditional co-occurrences of signals. The suggested analysis provides a framework for the understanding of various aspects of cell-to cell communication, such as structure-function relationship of regulatory peptides, multiple receptor subtypes, plurichemical transmission, and transduction networks. The data discussed are consistent with the role of regulatory peptides as signals in a universal structured code for biological communication. PMID- 1872392 TI - Glutamine and fatty acid oxidation are the main sources of energy for Kupffer and endothelial cells. AB - This study assessed and compared the rate of glucose utilization, activity of the hexose-monophosphate shunt (HMS), and the oxidation of glutamine, lactate, and palmitate in Kupffer (KC), endothelial (EC), and parenchymal liver cells (PC). Cells were isolated by collagenase and pronase digestion followed by centrifugal elutriation. The freshly isolated cells were incubated in the presence of 5 mM glucose, 0.5 mM glutamine, 1 mM lactate, and 0.4 mM palmitate, and the oxidation rate of individual substrates was determined by the measurement of 14CO2 production. Glucose utilization was assessed by detritiation of [2-3H]glucose. Glucose flux through HMS was 2.6, 1.6, and 0.72 nmol.h-1.mg protein-1 in KC, EC and PC, respectively. The oxidation rate of palmitate in PC (3.5 nmol.h-1.mg protein-1) was about twofold greater than in nonparenchymal cells. Glutamine oxidation was 6.1, 4.2, and 2.1 nmol.h-1.mg protein-1 in KC, EC, and PC, respectively. In contrast, oxidation of exogenous lactate by PC (32.1 nmol.h-1.mg protein-1) was about seven- to eightfold greater than by KC or EC. Presence of prevailing lactate concentrations did not inhibit glucose oxidation in these cells, while it attenuated glucose utilization by PC. Our data show that in the presence of a physiological substrate mixture, less than 20% of the ATP generated from exogenous substrates is derived from glycolysis in KC or EC. Oxidation of glutamine and palmitate are the main sources for energy in these cells. In PC, however, lactate and palmitate oxidation is responsible for approximately 90% for the ATP production derived form the oxidation of exogenous substrates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872394 TI - Relation between postprandial gastric emptying and cutaneous electrogastrogram in primates. AB - The relation between the cutaneous electrogastrogram (EGG) and gastric emptying was investigated in six rhesus monkeys. Gastric emptying was measured using scintigraphy after administration of two 80-ml mixed solid liquid meals (1.5 and 5.0 kcal/kg) tagged with 99mTc-sulfur colloid and 111In-diethylenetriamine pentaacetic acid. Six epigastric bipolar recordings of the EGG were concurrently obtained, digitized, and band-pass filtered. Portions of the signal with motion artifacts were automatically detected and excluded using two microwave motion sensors. During the early postprandial period, gastric emptying was greater after the 1.5-kcal/kg meal than after the 5-kcal/kg meal, and EGG amplitude increased significantly compared with fasting only after the 1.5-kcal/kg meal. Both emptying and EGG amplitude subsequently decreased after the 1.5-kcal/kg meal, whereas these two parameters increased after the 5-kcal/kg meal. As a result, EGG amplitude was significantly correlated with gastric emptying of solids in all six animals. In contrast, EGG frequency was not significantly different between the two meals and was not correlated with emptying. These results indicate that both the EGG and gastric emptying are modified differently by meals with different caloric contents and that the EGG may represent a useful, although indirect, index of gastric emptying. PMID- 1872393 TI - Effects of glycerol tripalmitate and glycerol trioleate on intestinal absorption of glycerol tristearate. AB - The goal of the present study was to determine 1) whether the poor digestion and absorption of glycerol tristearate (TS) that we observed previously is due to amount fed and 2) whether the digestion, absorption, and lymphatic transport of TS is affected by the presence of either a saturated fat [glycerol tripalmitate (TP)] or a monounsaturated fat [glycerol trioleate (TO)]. Three groups of intestinal lymph fistula rats were used. Group A was fed a lipid emulsion containing 12.5 mumol of TS (labeled as [glyceryl-1,3-14C]tristerate), 7.8 mumols of egg phosphatidylcholine, and 57 mumols of sodium taurocholate in 3 ml of phosphate-buffered saline per hour for 8 h. Group B rats were fed the same emulsion as group A, but with 12.5 mumols of TO added. Group C rats had 12.5 mumols of TP instead of TO added to the group A emulsion. The lymphatic radioactivity and triglyceride outputs were significantly lower in group A, with group C next and group B having the highest outputs. Significantly more TS remained in the lumen of the group A rats compared with groups B and C. The majority of the radioactivity in the lumen was still in the TS form in all three groups, indicating poor lipolysis. However, once the fatty acid and monoglyceride were absorbed, the reesterification process was similar in all three groups. When we studied the ability of the three groups of animals to transport the absorbed lipid into lymph (lymph transport index), both groups B and C were significantly better than group A rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872395 TI - Effect of Pluronic L81, a hydrophobic surfactant, on intestinal mucosal cholesterol homeostasis. AB - Addition of triglyceride and phospholipid to sodium taurocholate when chylomicron output was blocked by L81 did not increase lymphatic total cholesterol output or mucosal unesterified (UC) content more than with sodium taurocholate alone, but mucosal esterified cholesterol (CE) was increased slightly. In these animals with defective chylomicron formation, excess cholesterol accumulated in the intestinal mucosa mainly as CE. The mucosal cholesterol content of animals with normal chylomicron transport expanded during cholesterol and triglyceride absorption, and the expansion led to increased lymphatic secretion of CE. These animals accumulated significantly less CE in their mucosa than did rats treated with L81, but had about the same amount of mucosal UC. However, the overall uptake of cholesterol from the lumen, as determined by either radioactivity or mass of cholesterol in mucosa and lymph, was significantly less in the L81 rats. Also, more radioactive cholesterol remained in the lumen of the L81-treated rats. Finally, the data on specific activities of free and esterified cholesterol showed that the mucosal cholesterol derived from the lumen does not mix evenly with the free cholesterol pool in the enterocytes and is preferentially esterified for export in lymph as triglyceride-rich lipoprotein. PMID- 1872396 TI - Method for prolonged ambulatory monitoring of high-amplitude propagated contractions from colon. AB - This study monitored high-amplitude propagated contractions (HAPCs) in ambulating subjects over a 24-h period using a new ambulatory recording system. Twelve healthy volunteers aged 34 +/- 5.96 yr participated. Approximately 12 h after a Colyte bowel prep, a small catheter (OD less than 3 mm), containing three solid state pressure transducers spaced 5 cm apart, was positioned by flexible sigmoidoscope at 40-50 cm from the anal verge. A battery-operated data recorder sampled the pressure at each port at 1 Hz and stored the values on all ports if any port exceeded 75 mmHg. At the conclusion of the 24-h period, an X-ray was taken to confirm the location of the catheter. Fifty-four percent of all HAPCs preceded a bowel movement by less than or equal to 1 h. Forty-nine percent of all HAPCs occurred within 1 h after a high-fat meal, and 33% occurred within 1 h of morning awakening. Reverse propagated waves, not previously described in the colon, were observed in three individuals. Spontaneous high-amplitude caudally propagated contractions occur 6.9 +/- 1.5 times/24 h in the sigmoid colon in ambulating asymptomatic individuals and are temporally related to defecation and meals. Peristaltic activity is decreased during sleep. This recording technique was reliable and well tolerated in all participants. PMID- 1872397 TI - Developmental expression of intestinal surfactant-like particles in rats. AB - We have reported the appearance of surfactant-like particles enriched for intestinal alkaline phosphatase and phosphatidylcholine within enterocytes and in the lumen of adult fat-fed rat intestine. Because rat pulmonary surfactant decreases in abundance during the first postnatal days, we examined the developmental expression of these intestinal particles in suckling rats. Electron microscopy revealed abundant particles in 1-day-old rats within and surrounding the villus enterocytes, declining in frequency by day 14. Phosphatidylcholine content, alkaline phosphatase, sucrase-isomaltase, and lactase activity in particles peaked 1 day after birth, declining rapidly to adult levels by day 3 of life, except for sucrase, which peaked again after weaning. The postnatal developmental profile of the same brush-border-associated enzymes was totally different. Membrane fractions enriched for alkaline phosphatase and of similar density to rat surfactant-like particles were isolated from the small intestine of an amphibian (Xenopus laevis) and a fish (grass carp). Electron microscopy of the Xenopus membranes revealed unilamellar structures similar to the rat particles, but the carp membranes were of dissimilar morphology. We conclude that particles with surfactant-like properties in the rat intestine are ontogenically expressed like pulmonary surfactant; similar particles are evident only in animals with lungs. PMID- 1872398 TI - Reflex changes in intestinal tone: relationship to perception. AB - Using an original technique, we demonstrated a modulation of intestinal tonic muscular activity (intestinal tone) by intestino-intestinal reflexes. In 11 healthy volunteers we quantitated intestinal tone variations as changes in the air volume within a flaccid bag (12 cm long) located in the proximal jejunum and maintained at a constant pressure by an electronic barostat. Validation studies with glucagon showed significant intestinal relaxation (117 +/- 10% delta vol; P less than 0.05). In six healthy volunteers, graded balloon distensions (1 min duration at 10-min intervals in 8-ml stepwise increments) were randomly performed 8 cm orad, 8 cm caudad, and 20 cm caudad to the bag of the barostat. Perception was scored (0-6) by a questionnaire. Distensions at the three sites induced similar perception; at the threshold for discomfort (score greater than or equal to 5) distension also induced intestinal relaxatory responses (43 +/- 10%, 34 +/- 5%, and 32 +/- 4% delta vol from orad to caudad, respectively; P less than 0.05 for all). However, while unperceived orad distensions (13 +/- 2 ml) induced reflex relaxation (21 +/- 6% delta vol; P less than 0.05), 20-cm-caudad distensions at higher levels (16 +/- 2 ml, 2.7 +/- 0.5 perception score; P less than 0.05) did not (1 +/- 7% delta vol). This dissociation between perception and intestinal tone reflexes suggests that both responses to intestinal distension are mediated by specific mechanisms. PMID- 1872399 TI - A novel transcellular transport pathway for non-bile salt cholephilic organic anions. AB - Non-bile salt cholephilic organic anions comprise a single class of nonhomologous ligands having a range of hydrophobicity. Hydrophobicity enhances the hepatic extraction of cholephiles as well as their partitioning into secreted biliary lipid particles. When hydrophobicity is correlated with patterns of biliary excretion for studying transcellular transport, however, the more hydrophobic probes are unsuitable. Specifically, with the isolated perfused rat liver technique, the excretory times for sulfobromophthalein and rose bengal were significantly longer compared with that for the much more hydrophilic analogue phenol red (PR), which showed only a single, nearly symmetrical excretory peak at 10 min. Colchicine affected the apparently well-defined PR pathway only at a saturation dose (10,000 times the tracer dose). In contrast, the effect of a different perturbant, monensin, was striking at a tracer dose of PR, but was less evident at a saturation dose. The combined administration of colchicine and monensin had no additive inhibitory effect on PR excretion at tracer doses. At a saturation dose of PR, where monensin is less inhibiting, however, a significant additive inhibitory effect was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872400 TI - Vasopressin and A23187 stimulate phosphorylation of myosin light chain-1 in isolated rat hepatocytes. AB - Vasopressin (VP) and other hormones that elevate intracellular Ca2+ concentration also increase tight junctional permeability in the liver cell. Data derived from study of other tissues suggest that microfilaments are instrumental in regulating tight junctional permeability. By analogy to microfilament contraction in smooth muscles, it is likely that the transduction pathway for these hormones involves Ca(2+)-stimulated complex formation between calmodulin and myosin light chain (MLC) kinase with activation of this latter enzyme. MLC kinase then phosphorylates MLC, which, in the presence of actin, exerts adenosinetriphosphatase activity and produces microfilament contraction. This transduction pathway in the hepatocyte remains speculative. To demonstrate the likelihood of this pathway, we stimulated isolated hepatocytes with 10(-8) M VP and assayed MLC phosphorylation. We did this by immunoprecipitation of myosin from homogenates of liver cells prelabeled with [32P]-orthophosphate. We used a polyclonal antibody raised in rabbits against rat liver cell myosin. Our data demonstrate that VP is a potent stimulator of MLC phosphorylation. Maximal rises in intracellular Ca2+ and maximal MLC phosphorylation occur within 40 s of VP administration. The dose-response curve for MLC phosphorylation by VP is similar to that for tight junctional permeabilization in perfused liver with maximal effect at about 10(-8) M VP. The calcium ionophore A23187 also stimulated MLC phosphorylation. MLC phosphorylation, therefore, is at least coincident with, and probably responsible for, tight junctional permeabilization caused by elevation of intracellular Ca2+ in the liver cell. PMID- 1872401 TI - Gastric HCO3- secretion: relationship with Na+ secretion and effect of acetazolamide in humans. AB - We examined the relationship between gastric HCO3- and Na+ secretion under fasting and sham-fed conditions in nine healthy men and also evaluated the effect of the carbonic anhydrase inhibitor acetazolamide on gastric secretion of HCO3- and Na+. Secretion of H+, K+, and Cl- were also measured. Gastric HCO3- secretion rates under fasting and sham-fed conditions closely paralleled Na+ secretion rates. A maximally tolerated intravenous dose (10 mg/kg) of acetazolamide significantly inhibited H+, Cl- and K+ secretion but did not significantly affect Na+ or HCO3- secretion. Thus the gastric mucosa secretes HCO3- and Na+ in parallel in humans both under fasting and sham-fed conditions. Relative to parietal secretion of HCl, nonparietal secretion of HCO3- and Na+ is resistant to carbonic anhydrase inhibition. PMID- 1872402 TI - Role of chloride ions in liver cell volume regulation. AB - Hypotonic swelling of liver cells is followed by regulatory volume decrease (RVD), which has been shown to involve facilitated release of K+. In this study, the role of C1- in RVD was examined by videoplanimetric analysis of cell volume and measurement of membrane potential (Vm) and resistance (Rm) in single isolated rat hepatocytes, and by measurement of 36Cl efflux in the isolated perfused liver preloaded with the isotope. Liver cells subjected to hypotonic stress by removal of 50 mM external NaCl (70% of control osmolality) swelled from an initial volume of 6.68 +/- 0.77 to 8.27 +/- 0.88 pl (24.3 +/- 3.4% increase) within 1 min and exhibited RVD at an initial rate of 0.26 +/- 0.01 pl/min. A step decrease in external Cl- accelerated the initial rate of RVD to 0.53 +/- 0.08 pl/min. RVD was abolished in cells that had been depleted of Cl-. Vm and Rm displayed biphasic responses to hypotonic stress. An initial (less than 15 s) hyperpolarization of Vm from -35.4 +/- 2.2 to -38.8 +/- 2.6 mV was followed by a gradual depolarization reaching -30.2 +/- 2.0 mV by 1 min. In parallel, Rm initially (less than 15 s) increased from 101 +/- 13 to 121 +/- 17 M omega (19 +/- 3% increase) and then declined to 55 +/- 4 M omega (59 +/- 4% of initial Rm) within 1 min. These changes were reversible upon return to isotonicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872403 TI - Hepatic processing of recombinant human renin: mechanisms of uptake and degradation. AB - Biologically active 125I-Bolton-Hunter-labeled recombinant human renin (BH-renin) was used to study hepatic processing of renin both in vivo in bile fistula rats and in vitro in isolated perfused rat livers. BH-renin was composed mainly (80%) of a form that bound to concanavalin A-agarose (CB-renin). Twenty minutes after femoral venous injection of CB-renin in vivo, 47% of injected radiolabel was present in liver. Hepatic uptake of CB-renin was inhibited in a dose-dependent manner by mannosylated bovine serum albumin (MBSA) and mannan, but was unaffected by asialofetuin and mannose 6-phosphate. MBSA also significantly inhibited the plasma disappearance of endogenous renin in kidney-ligated rats. Cell separation techniques and light microscopic autoradiography showed that CB-renin was preferentially cleared by hepatic nonparenchymal cells via the mannose receptor, but was also cleared by hepatocytes via an unidentified mechanism. Tissue fractionation demonstrated that after injection of CB-renin, radiolabel was concentrated in lysosome-enriched liver fractions. In the liver, CB-renin was rapidly degraded to trichloroacetic acid-soluble fragments, which accumulated in urine and bile. Leupeptin, an inhibitor of lysosomal proteases, decreased degradation of CB-renin by 60%; vinblastine and colchicine, microtubule binding agents, each inhibited CB-renin degradation by 40%. Our results show that the liver plays a major role in the regulation of plasma renin levels via clearance by the mannose receptor on nonparenchymal cells and subsequent degradation in lysosomes. PMID- 1872404 TI - Contraction and accommodation of guinea pig duodenum in vitro. AB - Because duodenal resistance to gastric emptying depends in part on duodenal capacity, we examined the changes of duodenal diameter, length, and luminal pressure that occur in response to injection of bolus volumes. Filling the duodenum led to a powerful, nonpropagating contraction of the duodenum. After the end of filling, sequential duodenal segments widened and duodenal pressure and length returned to baseline; i.e., there was accommodation. Accommodation was volume dependent and ceased at volumes greater than or equal to 1.2 ml. The entire duodenum unfolded almost immediately and the initial increase of pressure and length was abolished when the duodenal musculature was inhibited by exposure to tetrodotoxin or to Ca(2+)-free solution. Pressures and pressure accommodation were larger, occurred earlier, and lasted longer when the duodenal musculature was stimulated by exposure to carbachol. Filling of the duodenum from the distal end led to rapid distribution of the bolus through the duodenum and to accommodation similar to that seen with proximal filling. However, phasic duodenal contractions were less powerful on distal than on proximal injection. Spontaneous phasic contractions of the duodenum were accompanied by a similar sequence of changes in duodenal configuration as was observed with filling. We conclude that 1) the duodenum adjusts the tension of its walls at small volumes, and beyond this is fairly rigid; 2) filling the duodenum triggers contraction responses similar to those that occur with spontaneous contractions; and 3) the direction from which the duodenum is filled does not affect its accommodation. We postulate that the filling response of the duodenum may critically affect gastric emptying. PMID- 1872405 TI - Effect of UDCA on intracellular and biliary pH. PMID- 1872406 TI - Lung surfactant protein SP-C from human, bovine, and canine sources contains palmityl cysteine thioester linkages. AB - Lung surfactant is a complex mixture of lipids and proteins that coats the alveoli to reduce surface tension and prevent airspace collapse. One of the principal protein constituents, surfactant protein C (SP-C), has been characterized following isolation from human, canine, and bovine sources. In each species, this highly hydrophobic protein is composed of 33-35 amino acids, the differences being due to NH2-terminal heterogeneity. A COOH-terminal leucine is conserved throughout. The cysteines in each species were found by fast atom bombardment mass spectrometry to be present as thioesters of palmitic acid. Acylation of recombinant SP-C with palmityl coenzyme A, followed by characterization before and after release of the acyl group with 1,4 dithiothreitol, provided corroborating evidence for the native structure. PMID- 1872407 TI - Neutrophil chemoattractant production by cultured serotonin-stimulated bovine and human endothelial cells. AB - Recent studies have demonstrated that serotonin (5-HT) is avidly taken up and metabolized by vascular endothelial cells (EC) and have suggested that 5-HT may contribute to inflammatory responses. Because EC can produce neutrophil cytokines among their biologically active molecules, we hypothesized that the interaction of 5-HT and EC might cause production of such a cytokine. Using a modified Boyden chamber assay, we found that cultured bovine aortic (BA), bovine pulmonary arterial (BPA), and human umbilical vein (HUV) EC incubated with 5-HT produced a neutrophil chemoattractant (NCA). The NCA was predominantly chemotactic, was not stored in an active form, appeared within 5 min of incubation with 5-HT, and required de novo protein synthesis for its appearance. The mechanism of NCA production was different in the three types of EC examined. Elaboration of NCA and BAEC and HUVEC was apparently mediated by 5-HT1 receptors and did not require uptake of 5-HT, whereas its elaboration from BPAEC required 5-HT uptake and was apparently mediated by 5-HT2 receptors. Incubation with three different lipoxygenase inhibitors blocked production of NCA, whereas incubation with a cyclooxygenase inhibitor did not. Further characterization of the NCA demonstrated that it was a mixture of several different chemotactic lipids and was distinct from other lipid or phospholipid neutrophil chemoattractants. These studies suggest that the interaction of the platelet-release product, 5-HT, with the adjacent endothelium results in the production of a chemoattractant that could affect neutrophil accumulation at sites of inflammation. PMID- 1872408 TI - Effects of intratracheal endotoxin administration on hamster lung glycosaminoglycans. AB - Incorporation of [3H]glucosamine and 35S into glycosaminoglycan (GAG) was measured in hamster lung explant cultures at 0, 1, 4, and 24 h after a single endotracheal instillation of Escherichia coli endotoxin. Lung content of GAG was measured in a second group of treated animals over an 8-day period. Albumin was detected after endotoxin treatment in bronchoalveolar lavage fluid at 24 h but was not found in lavage fluid 7 days later or in lavage fluid of saline-treated animals. Over the initial 24 h, increasing amounts of radiolabeled precursor molecules were incorporated into all classes of GAG. Proportionally more radiolabel was incorporated into hyaluronic acid and chondroitin sulfate, and less was incorporated into heparan sulfate. The proportion of radiolabel incorporated into dermatan sulfate did not change. Total lung content of hyaluronate and chondroitin sulfate was elevated at 24 h but was returning to baseline by 8 days. The lung content of dermatan sulfate was increased at 8 days; lung content of heparan sulfate did not change over the 8-day study period. Elevations in the amount of explant heparan sulfate that bound to antithrombin III (AT III) were found at 1 h after both saline and endotoxin treatment. Radiosulfated heparan sulfates were found in blood from hamsters treated with endotoxin 1 h previously; these heparan sulfates did not bind to AT III. However, blood contained heparin-like activity. We conclude that endotoxin differentially alters the metabolism of each class of hamster lung glycosaminoglycans and that metabolic changes begin very rapidly after endotoxin exposure. The relation of pulmonary endothelial injury to the presence of heparin-like activity in blood is not yet clear. PMID- 1872409 TI - Regulation of the contractile element of airway smooth muscle. AB - Smooth muscle of the mammalian airways controls airway diameter and resistance to airflow. Smooth muscle tone is in turn controlled by a variety of external signals that are transduced to useful work by contractile proteins. The protein components of the contractile element of airway smooth muscle are similar to those found in other smooth muscles and include actin, myosin, tropomyosin, caldesmon, and calponin. There has been significant recent progress in studies of contractile system regulation of airway smooth muscle. Regulation of myosin light chain kinase, identification of the sites phosphorylated on the regulatory myosin light chains, and the effect of myosin phosphorylation on stress development and crossbridge cycling rates have all been studied in some detail. We infer from these studies that besides myosin phosphorylation there is an important role for a thin filament Ca(2+)-dependent regulatory mechanism. The potentially important thin filament proteins caldesmon and calponin are present in tracheal smooth muscle and may be phosphorylated during contraction. The use of intracellular Ca2+ indicators to estimate changes in intracellular Ca2+ ([Ca2+]i) and the development of several skinned fiber preparations have broadened the scope of physiological studies with airway smooth muscle and have suggested that the contractile element sensitivity to Ca2+ is not fixed but might be modulated by undefined messengers or excitation-contraction pathways. This adds an additional challenge to the continuing effort to define the messengers and regulatory proteins that couple activation of membrane receptors to the contractile element in airway smooth muscle. PMID- 1872410 TI - Biphasic contractile response of pulmonary artery to hypoxia. AB - Isolated perfused lungs exposed to low O2 exhibit a hypoxic pulmonary vasoconstriction response that is transient in nature. The purpose of this study was to determine whether the isolated pulmonary artery behaves similarly in response to hypoxia. Rat pulmonary arterial rings were placed in tissue baths (37 degrees C, air-5% CO2, pH = 7.4) and attached to force transducers. Maximum contractile responses (Po) to high K+ were elicited. After washout, arterial rings were submaximally contracted and made hypoxic (PO2 = 33.7 +/- 1.3, pH = 7.38 +/- 0.01). Aortic rings were used to obtain comparative data. The isolated pulmonary arterial hypoxic response was biphasic, displaying an initial rapid contraction of short duration (phase 1) then, before complete relaxation of this first response, a second slow but sustained contraction occurred (phase 2). Aortic rings did not exhibit a biphasic response, but showed only an initial short contraction followed by complete relaxation. The contractile response of the pulmonary artery was diminished when the endothelium was rendered nonfunctional. However, the phase 2 response was not endothelium dependent. Neither inhibitors of the lipoxygenase or cyclooxygenase pathways nor scavengers of extracellular reactive oxygen species had any effect on the biphasic hypoxic response. Pulmonary arterial hypoxic contractions were blunted when glucose was absent and appear to be dependent on glycolytic ATP. Results of this study show that hypoxia causes a biphasic contractile response of pulmonary arterial muscle and that two different mechanisms appear to be involved, since the transient phase 1 response is endothelium dependent, whereas the sustained contraction of phase 2 is endothelium independent. PMID- 1872411 TI - Ontogeny of ion transport across fetal pulmonary epithelial cells in monolayer culture. AB - The transition of the fetal lung from a fluid-secreting to a fluid-absorbing organ is dependent on ion transport across the pulmonary epithelium. This study examined the ion transport characteristics of distal pulmonary epithelial cells isolated from rat fetuses in late gestation and maintained in differentiation arrested monolayer cultures. The response to inhibitors of active ion transport suggested the presence of apical to basolateral Na+ transport in monolayers derived from each gestational age. However, amiloride inhibition of short-circuit current (Isc) varied with gestational age, decreasing Isc by 30% in monolayers derived from day 18 fetuses and by 55% in monolayers from day 21 fetuses. A portion (10%) of the residual Isc remaining after amiloride addition to monolayers from day 18 fetuses could be inhibited by bumetanide, suggesting the induction of net Cl- transport. Ion-substitution experiments confirmed the presence of Na+ and inducible Cl- transport mechanisms in monolayers from day 18 fetuses and only Na+ transport mechanisms in monolayers from day 21 fetuses. beta Adrenergic stimulation increased Isc but maintained the age-dependent characteristics of Na(+)- and Cl(-)-dependent ion transport. In summary, monolayer cultures of fetal pulmonary epithelial cells exhibit age-dependent differences in ion transport properties that are consistent with a transition or maturation of the distal pulmonary epithelium from an epithelium capable of Na+ absorption and Cl- secretion preterm to one capable of only Na+ absorption at term. PMID- 1872412 TI - Factors affecting distribution of alveolar surfactant during resting ventilation. AB - Few studies have been done to establish the ventilatory factors affecting alveolar surfactant under resting conditions. Experiments in which ventilatory variables were recorded for 4 h were performed in 12 adult cats breathing spontaneously under pentobarbital sodium anesthesia. After the animals were killed and bronchoalveolar lavages (BALs) were performed, the resulting fluid was subjected to differential centrifugation and determinations of proteins, phospholipids (PL), and disaturated phosphatidylcholine (DSPC). Pellet P1+2 was obtained by two centrifugations at 140 g; the supernatant was centrifuged at 1,000 g to obtain pellet P3 and subsequently at 60,000 g to obtain P4. Pellets P3 and P4 had the higher contents of PL and DSPC. Bivariate and multivariate correlational analyses indicate that 1) total PL in BAL was not related to any of the ventilatory variables studied, 2) PL in P3 and P4 fractions was directly correlated to the physiological range of variations in the frequency of large spontaneous gasps (fL), and 3) PL in P1+2 fraction was inversely related to fL. Cats subjected to bilateral section of carotid nerves, although presenting reduced chemosensory drive and ventilatory chemoreflexes, did not exhibit significant differences in resting ventilatory variables nor in alveolar surfactant components. Present results indicate that the total content of alveolar surfactant is not modified by ventilatory variations within physiological range but that the spontaneous occurrence of large gasps increases the proportion of more active forms of alveolar surfactant. This may mediate the role of augmented breaths in keeping lung compliance and preventing atelectasis under resting ventilatory conditions. PMID- 1872413 TI - Method for rapid evaluation of topically applied agents to cystic fibrosis airways. AB - The proposal is to target a single maxillary sinus for treatment with agents designed to reverse or ameliorate the cystic fibrosis (CF) defect in airway mucosa, with the opposite sinus serving as a control. Selected CF patients have undergone maxillary antrostomy and antibiotic lavage to help relieve severe pulmonary disease and chronically impacted and infected sinuses. After treatment, the mucosa in the maxillary sinuses of these patients are accessible and can be bathed with fluids introduced via the stomas with procedures that restrict the fluid to a single sinus. The ability of an agent to reverse mucosal pathology can therefore be determined easily with the mucosa of the contralateral sinus serving as a control. Electrophysiological properties, amounts and composition of fluid and mucus, immune functions, and bacterial colonization can be measured accurately and repeatedly. The consistent observation that sinus involvement in CF is near universal and bilaterally symmetric offers a unique opportunity for a simultaneous within-subject, double-blinded control paradigm. This approach should speed evaluation of any agent designed to improve airway mucosal function. PMID- 1872414 TI - Control of type I collagen formation in the lung. AB - Type I collagen is a major structural protein in the lung, the accumulation of which is stimulated during certain inflammatory reactions in the lung. Accumulating evidence suggests that type I collagen formation parallels changes in steady-state mRNA levels. Specific inflammatory substances modulate transcription of collagen genes and stabilization of collagen mRNA in vitro. However, the precise role for any particular mediator during fibrotic processes is difficult to identify because of the complex nature of the inflammatory reaction and potential interaction among mediators. The signal transduction mechanisms that regulate collagen accumulation remain to be defined. This review focuses on the regulation of collagen accumulation in the lung by specific inflammatory substances. PMID- 1872416 TI - Mechanism underlying ozone-induced in vitro hyperresponsiveness in canine bronchi. AB - The effects of ozone inhalation on the contractility of canine bronchi and the mechanisms underlying any changes observed were investigated. Ozone inhalation caused acetylcholine airway hyperresponsiveness in vivo. Isolated segments of bronchi (3rd to 5th order) from dogs previously exposed to ozone (or normal air) were mounted in organ baths. Contractile responses to electrical field stimulation (FS) in all tissues decreased in magnitude over time (measured at 10, 120, 210, and 300 min after mounting tissues in the organ baths); responses to 150 mM KCl did not show such a progressive decrease. Ozone inhalation produced a dramatic enhancement of FS responses, a smaller enhancement of responses to carbachol (10(-8)-10(-4) M), and no change in responses to KCl (150 mM). In the presence of 10(-5) M indomethacin, all responses were enhanced and tended to increase in magnitude over time; indomethacin also abolished the differences in responsiveness between the control and ozone-exposed tissues. In the presence of the thromboxane receptor antagonist L-670,596 (10(-8) M), the magnitudes of all FS responses showed a progressive decrease over time while KCl responses did not; again, the differences in FS responses between control and ozone-exposed tissues were decreased or made insignificant. In conclusion, ozone produced airway hyperresponsiveness in vivo and hyperresponsiveness in canine bronchi in vitro via decreased prejunctional and postjunctional inhibition (likely mediated by prostaglandin E2) and increased prejunctional excitation mediated by thromboxane A2. However, direct measurements of mediator release should be carried out to reach a firm conclusion. PMID- 1872415 TI - Cigarette smoking induces an elastolytic cysteine proteinase in macrophages distinct from cathepsin L. AB - Degradation of the interstitium of the lung by elastolytic enzymes is thought to be a critical component of the pathogenesis of emphysema. Alveolar macrophages are increased in numbers in cigarette smokers and contain the elastolytic cysteine proteinase cathepsin L. We sought to determine if cigarette smoking induces a change in cathepsin L levels in alveolar macrophages which would, in turn, alter the expression of elastolytic activity. Lysates of smokers' macrophages, assayed at pH 5.50, degraded more than seven times as much [3H]elastin as did lysates from nonsmokers' macrophages (44 +/- 20.8 vs. 6 +/- 1.6 micrograms.10(6) cells-1.24 h-1). Little or no activity was demonstrable at neutral pH. Immunoblots of macrophage lysates demonstrated that smokers' cells contain 3.7 +/- 1.1 times as much 25-kDa cathepsin L antigen as nonsmokers' cells. However, as judged by active site labeling, levels of active cathepsin L in smokers and nonsmokers are indistinguishable, suggesting that most of the 25 kDa antigen found in smokers' macrophages is inactive. Inhibitors of cathepsin L had little effect on lysate elastolytic activity, confirming that an enzyme other than cathepsin L is responsible for the increased elastolytic activity seen in smokers' macrophages. Further experiments demonstrated that this second enzyme(s) has a profile of inhibition indicating that it is a cysteine proteinase with optimal activity at pH 5.50. It is this second elastolytic cysteine proteinase(s) that is induced by exposure to cigarette smoke and is responsible for the sevenfold increase in elastolytic activity found in smokers' macrophage lysates. PMID- 1872417 TI - Expression of SV40 T antigen under control of rabbit uteroglobin promoter in transgenic mice. AB - The rabbit uteroglobin gene is expressed in the lungs and reproductive tracts of male and female rabbits. To examine whether the promoter region of the uteroglobin gene could be used to target a heterologous gene to the lungs of transgenic mice, a fusion gene consisting of 3.3 kb of the 5'-flanking region of the rabbit uteroglobin gene and the large T antigen gene of the SV40 virus was constructed and microinjected into the pronuclei of one-cell mouse embryos. Eleven founder transgenic mice (5 female and 6 male) were generated. Seven of these mice developed bronchioalveolar neoplasms. Four of the founder males also developed primitive undifferentiated urogenital tract tumors. One founder female and one female offspring of a founder male developed glandular paraovarian tumors. Northern analysis revealed that the predominant site of expression of the transgene was the lung. Immunohistochemical staining showed T antigen predominantly in epithelial cells lining the bronchioles, the submucosal glands of the trachea, and the neoplasms. There appeared to be a high level of mosaicism for the transgene in the founder mice, with poor transmission of the transgene to subsequent generations. This suggests that, under the control of the uteroglobin promoter, the T antigen gene may be lethal to the fetus. PMID- 1872418 TI - Structural and functional changes of surfactant protein A induced by ozone. AB - The major surfactant protein SP-A is thought to play an important role in the regulation of the structure and the metabolism of pulmonary surfactant. We investigated whether this protein may be a target in ozone toxicity. Several properties were studied that are probably relevant to the physiological functions of SP-A. In vitro exposure of human and canine SP-A to ozone led to decreases in 1) self-association of SP-A, 2) SP-A-mediated lipid aggregation, and 3) binding of SP-A to immobilized mannose. SP-A was neither degraded nor cross-linked by ozone exposure. Exposure of canine SP-A to ozone led to an increase in the apparent molecular weight of monomeric SP-A. Human SP-A did not show this change. Oxidation of methionine and tryptophan residues in canine SP-A was detected following ozone exposure. Reactions of ozone with other amino acid residues were not observed. The impairments of structure and properties of SP-A may contribute to the toxic action of ozone in the lungs. PMID- 1872419 TI - Hydrogen peroxide production by alveolar type II cells, alveolar macrophages, and endothelial cells. AB - Extracellular H2O2 release and intracellular H2O2 production were determined in rat lung alveolar macrophages, rat alveolar type II cells, and cultured bovine aortic endothelial cells. Isolated macrophages (5 h ex vivo) released 3.1 +/- 0.09 nmol H2O2.min-1.mg cell protein-1, freshly isolated (5 h ex vivo) type II cells released 0.7 +/- 0.07 nmol H2O2.min-1.mg protein-1, and cultured endothelial cells released 0.06 +/- 0.005 nmol H2O2.min-1.mg protein-1. The rate of extracellular H2O2 release decreased rapidly over time in both fresh macrophages and freshly isolated type II cells. When the measurements were repeated at different times ex vivo, the decrease was greater than 20%/h, and H2O2 release was almost undetectable 12 h ex vivo. The decrease occurred while lactate dehydrogenase release, catalase activity, and intracellular H2O2 production remained unchanged. Catalase activity was 59.3 +/- 4.9 nmol O2 produced.min-1.mg protein-1 in type II cells, 13.2 +/- 1.8 in macrophages, and 11.4 +/- 2.7 in endothelial cells. Aminotriazole is a compound that inhibits catalase in the presence of H2O2 at a rate that is proportional to the rate of intracellular H2O2 production in or near peroxisomes. Incubation of the cells with aminotriazole led to a rapid inhibition of catalase. In 15 min the reduction of catalase activity was 69% in type II cells, 53% in macrophages, and 37% in endothelial cells. When freshly isolated type II cells were exposed to hyperoxia (95% O2) for 30 min, no changes in the rate of either intracellular H2O2 production or extracellular H2O2 release were seen. PMID- 1872420 TI - Composition changes in human tracheal cartilage in growth and aging, including changes in proteoglycan structure. AB - High-buoyant-density proteoglycans were extracted and purified from tracheal cartilage obtained from nine individuals aged 1-58 yr. Cartilage from young individuals contained one major species of extractable aggregating proteoglycan and very little link protein. Link protein concentration relative to proteoglycan was observed to increase during the first 14 years of life, consistent with the increased formation of proteoglycan aggregates that are stabilized by link protein, as the process of tracheal cartilage growth and airway lumen widening ends. With increasing age after maturity, two further populations of proteoglycans became more abundant; these were characterized by higher mobility in composite agarose-polyacrylamide gel electrophoresis. The ability of the proteoglycans to associate with hyaluronan decreased with increasing age, although members of each of the three proteoglycan species contained functional hyaluronan-binding domains. Link proteins showed evidence of increasing proteolysis with age. Hydroxyproline content of the cartilage decreased with age; total tissue glycosaminoglycan and water contents showed no significant changes. Altered proteoglycan charge density, proteoglycan size, and aggregation properties, as well as changes in distribution of proteoglycans, may contribute to the changes in cartilage biomechanics that are associated with age-dependent changes in human lung function. PMID- 1872421 TI - The anaesthetic management of congenital tracheal stenosis. AB - Congenital tracheal stenosis is a rare and potentially lethal condition. Two case reports are presented which demonstrate the problems encountered in the anaesthetic management of this condition. PMID- 1872422 TI - Acute mercury poisoning. AB - A case of deliberate self poisoning with approximately 7 g mercuric chloride (the lethal dose is about 1 g) is described. The patient died after 6 days despite the use of chelating agents, plasma exchange and intensive supportive therapy. The management of acute mercury toxicity is discussed. PMID- 1872423 TI - Williams syndrome: masseter spasm during anaesthesia. AB - A 4-year-old boy with Williams syndrome developed masseter spasm after halothane and suxamethonium. He did not develop malignant hyperthermia; the surgery was accomplished with a nontriggering anaesthetic and no further problems. PMID- 1872424 TI - Epidural blood patch for treatment of subarachnoid fistula in children. AB - A subarachnoid-cutaneous fistula developed in two children after the placement of a catheter in the subarachnoid space for drainage of cerebrospinal fluid. The management of this iatrogenic complication with epidural blood patch is described. PMID- 1872425 TI - Acute airway obstruction, hypertension and kyphoscoliosis. AB - An elderly woman developed acute respiratory obstruction after choking on a bolus of food. On rigid bronchoscopy no foreign body, or anatomical obstruction was seen, but airway obstruction recurred during emergence from general anaesthesia, and was thought to be functional in nature. A recurring airway obstruction followed, relieved by induction of anaesthesia and by sedation. This was subsequently demonstrated to be caused by a tortuous aorta which impinged intermittently on the anterior tracheal wall, as a result of kyphoscoliosis of the thoracic spine. We attribute the relief of airway obstruction by general anaesthesia to a reduction in arterial blood pressure. PMID- 1872426 TI - Accidental injection of ether into the epidural space. AB - Five ml diethyl ether was accidentally injected into the epidural space via an epidural catheter at the end of a Caesarean section. Immediately the patient felt a hot and burning pain in her legs that led to paraparesis, with a sensory level to T8. The patient showed bilateral recovery of both motor and sensory functions 4 hours after the accident. PMID- 1872427 TI - Anaesthesia for Proteus syndrome. AB - A 14-year-old boy with Proteus syndrome presented for orthopaedic surgery to his legs. No report in the literature exists on anaesthesia for this condition. Our patients posed airway problems that were managed by tracheal intubation under sedation using a fibreoptic bronchoscope. Anaesthesia was induced with thiopentone and maintained with nitrous oxide and isoflurane in oxygen. His lungs were ventilated mechanically throughout surgery, which was uneventful. PMID- 1872428 TI - Oxygen delivery systems--a comparison of two devices. AB - Two low-volume, variable performance oxygen delivery systems were compared in conscious spontaneously breathing volunteers. Oropharyngeal oxygen concentrations were measured during periods of nose and mouth breathing. The systems were studied at oxygen flow rates of 2 or 4 litres/minute. The performance of both systems was similar under the test conditions but the nasal catheter is preferable in terms of cost. PMID- 1872429 TI - Postoperative analgesia after triple nerve block for fractured neck of femur. AB - Fifty patients with fractured neck of femur that required surgical correction with either a compression screw or pin and plate device were randomly allocated to receive one of two anaesthetic techniques, general anaesthesia combined with either opioid supplementation or triple nerve block (three in one block) with subcostal nerve block. The nerve blocks significantly reduced the quantity of opioid administered after operation; 48% of these patients required no additional analgesia in the first 24 hours. Plasma prilocaine levels in these patients were well below the toxic threshold, and peak absorption occurred 20 minutes after the injection. No untoward sequelae were associated with the nerve blocks. PMID- 1872430 TI - Rhabdomyolysis and operating position. AB - Rhabdomyolysis during routine surgery was studied in three groups of patients who had surgery, with limited trauma to muscle, in the lateral and supine positions, and prone on the spinal frame. A range of blood tests was performed (before surgery, and on the first, third and seventh day after operation). These showed that a creatine kinase increase in the 24 hours and the early appearance of myoglobin in the serum were the best indicators. Rhabdomyolysis was associated with the lateral position and long lasting surgery. No blood test before surgery was of any predictive value. PMID- 1872431 TI - A district-wide anaesthetic audit. AB - A district-wide anaesthetic audit has been implemented by the Derby anaesthetic department. Data for every anaesthetic are collected on a specially designed audit form which is read into a computerised database using an optical mark reader. The implementation of the audit, problems encountered and some benefits realised are described. PMID- 1872432 TI - Anaesthesia for cataract surgery--time for change. PMID- 1872433 TI - A critical incident with the Ohmeda Excel 410 machine. PMID- 1872434 TI - Atropine or glycopyrronium?--a dangerous dilemma. PMID- 1872435 TI - Anaesthetists and trauma. PMID- 1872436 TI - A level vaporizer. PMID- 1872437 TI - Hazard with a Boyle vaporizer. PMID- 1872438 TI - Fixation of tracheal tubes. PMID- 1872440 TI - Incorrectly filled cylinders. PMID- 1872439 TI - Labelling on oxygen analysers. PMID- 1872441 TI - Potential hazard of central venous cannulation. PMID- 1872442 TI - Intravenous propofol anaesthesia using a computerised infusion system. PMID- 1872443 TI - Awareness during caesarean section. PMID- 1872444 TI - The Engstrom Elsa anaesthetic machine. PMID- 1872445 TI - Scavenging in the operating theatre. PMID- 1872446 TI - Defective spinal needle. PMID- 1872447 TI - Diagnostic fibreoptic bronchoscopy using the laryngeal mask. PMID- 1872448 TI - Amorous behaviour and sexual fantasy after anaesthesia or sedation. PMID- 1872449 TI - Elohes administration following an anaphylactoid reaction to Haemaccel. PMID- 1872450 TI - Epidural analgesia and hypotension. PMID- 1872451 TI - Use of the laryngeal mask airway in primary care. PMID- 1872452 TI - Visual disturbances after transurethral resection of the prostate. PMID- 1872453 TI - 'Bow-ties' in ITU. PMID- 1872454 TI - Foreign body in a laryngeal mask airway. PMID- 1872455 TI - The future development of chronic pain relief. PMID- 1872456 TI - Intra-operative patient-controlled sedation. AB - Patient-controlled sedation using propofol is described in 23 ASA 1 patients undergoing surgical extraction of third molars. Cardiovascular and respiratory stability was maintained and sedation was no deeper than full eyelid closure with prompt response to verbal command. Amnesia for the extractions was common (70%), but there was no significant amnesia for recovery room events. Intra-operative patient cooperation was good, postoperative patient satisfaction high and all patients stated they liked the self-administration and would use the same technique again. Propofol dose was correlated with both procedure length (r = 0.587; p = 0.003) and surgical difficulty (rs = 0.550; p = 0.010). PMID- 1872457 TI - Incremental spinal anaesthesia using a 32-gauge catheter. AB - Incremental spinal anaesthesia using a 32-gauge intrathecal catheter was studied in 13 males scheduled for transurethral resection of the prostate or repair of inguinal hernia. The spinal technique failed in four patients. Dose-response curves were obtained in the remaining nine patients using increments of 0.5% plain bupivacaine. The spinal block was extended safely and reliably without cardiovascular instability. No patient had any postoperative headache and all catheters were removed intact. PMID- 1872458 TI - Evaluation of local anaesthetic blockade of the lateral femoral cutaneous nerve. AB - An assessment of local anaesthetic blockade of the lateral femoral cutaneous nerve using a standard technique was made. The rate of successful blockade was high, but the area of sensory loss was inconsistent between patients and was more anterior and distal than described in textbooks of anatomy. PMID- 1872459 TI - Depth of extradural space and dural puncture. AB - The records of 3011 obstetric extradural blocks were examined to determine the depth of the extradural space and the relative risk of dural puncture. The overall incidence of dural puncture was 0.7%. A disproportionate number of punctures occurred when the space was superficial (1.45%), with a risk factor three times greater than that associated with normal depth spaces (0.48%). Caution is advised when infiltrating with local anaesthetics before extradural procedures, and when initially introducing the extradural needle. PMID- 1872460 TI - Echocardiographic assessment of the haemodynamic effects of propofol: a comparison with etomidate and thiopentone. AB - The haemodynamic effects of propofol (2 mg/kg), etomidate (0.2 mg/kg) and thiopentone (4 mg/kg) were studied in 30 ASA 1 and 2 patients in whom anaesthesia had been induced with midazolam 0.1 mg/kg, fentanyl 5 micrograms/kg, vecuronium 0.1 mg/kg and atropine 10 micrograms/kg, and maintained with nitrous oxide in oxygen. Arterial pressure was measured directly and left ventricular diameters were determined by transoesophageal echocardiography. Systolic blood pressure after propofol and thiopentone and the end-systolic quotient (systolic pressure/end-systolic diameter), a measure of inotropy, decreased. Fractional shortening (end-diastolic-end-systolic diameter/end-diastolic diameter) decreased only in the thiopentone group. Diastolic blood pressure and end-diastolic diameter (a measure of preload) did not change in any of the groups, and the etomidate group showed no changes in the haemodynamic variables measured. Propofol shows simultaneous negative inotropy and afterload reduction, while thiopentone is exclusively negatively inotropic. PMID- 1872461 TI - Venous and aortic porcine endothelial cells cultured under standardized conditions synthesize heparan sulfate chains which differ in charge. AB - The identification of a specific required carbohydrate structure for the antithrombin III binding site on heparin suggests that there may be specific structures in glycosaminoglycan chains which are necessary for other vascular functions of these carbohydrates. Determining that such differences exist requires a mechanism to isolate heparan sulfates from endothelial cells of specific vascular beds. The present report indicates that cultured venous and aortic endothelial cells synthesize heparan sulfate chains differing in charge density. There are two important conclusions from this work. (i) Endothelial cells from different blood vessels (i.e., vena cava and thoracic aorta) synthesize heparan sulfates which differ in negative charge and sulfation pattern. Specifically, aortic endothelial heparan sulfates have a higher negative charge than venous heparan sulfates. Differences are also observed in the nitrous acid degradation products of the heparan sulfates. (ii) Endothelial cells in culture retain the ability to synthesize different heparan sulfates in vitro after months of subculture under defined conditions. These results indicate that it is feasible to characterize heparan sulfates using cultured endothelial cells from a variety of vascular beds. PMID- 1872462 TI - A microprocessor-regulated constant voltage, current, wattage, and temperature electrophoresis power supply. AB - The analog control circuitry typically found in commercial electrophoresis power supplies was replaced by a digital microcomputer. Analog to digital converters were used to monitor the voltage applied to and current passed through an electrophoresis cell. Microcomputer programming was employed to compare converter input values with preselected operating parameters and then calculate a required output voltage. Timing sequences were generated through programming utilizing clocks located on the interface boards. A digital to analog converter was employed to apply a control voltage to a constant voltage power supply. This process was completed at least 20 times each second. BASIC programming subroutines were written to maintain constant voltage, current, power (wattage), and temperature. To these operating procedures, other techniques such as automated endpoint detection of isoelectric focusing and pulsed waveform outputs were easily added. This power supply containing a microcomputer system as the feedback element was shown to have a greater stability and versatility than conventional supplies. PMID- 1872463 TI - Mass spectrometric signature of S-prenylated cysteine peptides. AB - The fast atom bombardment mass spectra of peptides containing S-prenylated cysteine display signature fragmentations characteristic of this modified amino acid. The fragmentation is independent of the nature of the cysteine carbonyl substituent, easily differentiates prenyl from nonprenyl alkylation, and readily identifies the oligomer count of the prenyl. This screening method, which requires little time, effort, or material (compared with previous analysis methods based on chemical degradation), greatly facilitates the identification of these prenylated proteins. PMID- 1872464 TI - Proteosynthetic activity of immobilized Staphylococcus aureus V8 protease: application in the semisynthesis of molecular variants of alpha-globin. AB - The proteosynthetic activity of Staphylococcus aureus V8 protease (endoproteinase Glu-C) immobilized onto cross-linked agarose beads by reductive alkylation procedure has been investigated. The overall substrate specificity of the enzyme, as judged by peptide mapping of performic acid oxidized RNase A, as well as the high propensity of the protease to slice selectively the alpha-chain of hemoglobin (Hb) A at the Glu(30)-Arg(31) peptide bond at pH 4.0 and 37 degrees C was essentially unperturbed by the immobilization process. This high susceptibility of Glu(30) of the alpha-chain for proteolysis appears to be a consequence of the conformational aspects of the polypeptide in this region. The proteolysis of two mutant forms of alpha-chain, namely, those of Hb I (K16E) and Hb Sealy (D47H) by immobilized V8 protease at the Glu(30)-Arg(31) peptide bond proceeds with the same selectivity. The immobilized protease also retained the proteosynthetic activity, i.e., the ability to ligate the unprotected alpha globin fragments at the Glu(30)-Arg(31) peptide bond in the presence of 30% 1 propanol. The use of the insoluble enzyme simplifies the procedures for the construction of new semisynthetic, molecular variants of alpha-globin. The general applicability of the immobilized enzyme for protein semisynthesis has been demonstrated by the construction of a doubly mutated alpha-globin. The complementary fragments from two natural mutant forms of alpha-globin, viz., alpha 1-30 (K16E) from Hb I and alpha 31-141 (D47H) from Hb Sealy, are readily ligated to form the double mutant alpha 1-141 (K16E;D47H). PMID- 1872465 TI - Peptide mapping in sodium dodecyl sulfate-containing buffers: control of proteolytic cleavage by organic solvent. AB - Dimethylformamide (DMF) was found to enhance proteolysis in sodium dodecyl sulfate (SDS)-containing buffers. This effect was seen with both denatured and reduced proteins, which are insoluble in the absence of SDS, and with native proteins. The use of DMF and SDS to control proteolysis and solubility of proteins will be useful in amino acid sequence studies. PMID- 1872466 TI - [1-14C]oleate-labeled autoclaved yeast: a membranous substrate for measuring phospholipase A2 activity in vitro. AB - Radiolabeled, autoclaved yeast were tested as a substrate for mammalian phospholipase A2 activity because the only other membranous substrate used for this purpose, autoclaved Escherichia coli, totally lacks a major mammalian phospholipid, phosphatidylcholine. Candida albicans were grown in the presence of [1-14C]oleate and then autoclaved. Sixty three percent of the incorporated label was in yeast phospholipid, and more than 95% of that was in the 2-acyl position. The distribution of label in the yeast phospholipids (phosphatidylcholine and ethanolamine, -serine + -inositol, and phosphatidic acid corresponded closely to the chemical distribution of phosphorus in those phospholipids. Snake venom (Naja naja) and human synovial fluid phospholipase A2 hydrolyzed yeast phospholipid exclusively to release 14C-labeled fatty acid. When 50-60% of the yeast phospholipid was hydrolyzed, the radioactive fatty acids as determined by gas liquid chromatographic analysis were predominantly oleate (45%) and linoleate (greater than 54%). Hydrolysis of yeast phospholipid by both enzymes was near linear with protein and time under conditions of optimal pH (neutral-alkaline) and Ca2- (1-5 mM) previously reported for optimal hydrolysis of autoclaved E. coli phospholipid. N. naja phospholipase A2 showed less preference for phosphatidylethanolamine than -choline as liposomes or yeast phospholipid as compared to human synovial fluid phospholipase A2 which clearly preferred phosphatidylethanolamine to -choline as a liposome or yeast phospholipid. These results illustrate that radiolabeled phospholipids of autoclaved yeast, enriched in phosphatidylcholine, are readily hydrolyzed by snake venom and human nonpancreatic phospholipases A2 and may, therefore, be useful in the measurement of in vitro enzymatic activity. PMID- 1872467 TI - A method for mini-immunoblots that allows screening of large numbers of samples. AB - A method that allows the use of immunoblots as a screening test for large numbers of samples is described. Preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis is run to a separation distance of 2 cm and the samples are blotted onto nitrocellulose. One-millimeter-wide strips are cut and immobilized on double-sided tape. Adjacent strips are separated by plastic rods. After incubation with the first antibody, whole slides are processed together as in histology. The method has been successfully applied to the primary screening of hybridoma supernatants and is generally applicable in situations where large numbers of samples must be tested in a short time. PMID- 1872468 TI - A colorimetric assay for a pyridoxal phosphate-dependent beta-replacement reaction with L-cysteine: application to studies of wild-type and mutant tryptophan synthase alpha 2 beta 2 complexes. AB - We present an improved and simple direct assay for formation of inorganic sulfide from L-cysteine in a beta-replacement reaction catalyzed by tryptophan synthase. This method provides a useful enzymatic assay for pyridoxal phosphate-dependent beta-replacement reactions in which the amino acid substrate is L-cysteine and the cosubstrate is 2-mercaptoethanol. The assay should be applicable to similar reactions with L-cysteine and other cosubstrates. The method has several advantages over other methods which have been used to assay similar beta replacement reactions. The assay is highly reproducible and sensitive and is conveniently carried out in disposable 1.5-ml centrifuge tubes. The color remains stable for several hours. The thiol compounds L-cysteine and 2-mercaptoethanol do not interfere at the concentrations used. The method has useful applications to studies of the rates and reaction specificities of several other pyridoxal phosphate enzymes which catalyze beta-replacement reactions. We demonstrate the use of the method to study the effects of site-directed mutagenesis on the reaction specificity and mechanism of the tryptophan synthase alpha 2 beta 2 complex. PMID- 1872469 TI - Iodometric measurement of lipid hydroperoxides in human plasma. AB - Many assay techniques have been used to measure lipid hydroperoxides in plasma, including absorbance of conjugated dienes and reactivity with thiobarbituric acid. Because these measurements are not specific for lipid hydroperoxides, we modified an exisiting iodometric method to correct for interfering phenomena and to provide a more specific measurement of the lipid hydroperoxide content of plasma. To ensure reproducible extraction of hydroperoxides from the many possible forms in plasma, the plasma was treated to hydrolyze enzymatically cholesterol ester, triglycerides, and phospholipids, and the nonesterified fatty acid peroxides were then extracted with ethyl acetate. Extracted lipids were reacted with potassium iodide in acetic acid and methylene chloride, and the resulting triiodide ion (I3-) was measured spectrophotometrically. Correction for nonoxidizing chromophores was made after back-titration of the triiodide ion to iodide with sodium thiosulfate and other non-peroxide oxidants were estimated by their resistance to reduction with glutathione peroxidase. Recovery of added hydroperoxide standards provided routine validations of the procedure's efficiency. The method indicated that insignificant amounts of hydroperoxide may be in the less polar lipids, but the total amount of lipid hydroperoxide esterfied in the plasma lipids of apparently healthy humans may be as much as 4.0 +/- 1.7 microM. PMID- 1872470 TI - Characterization of N-linked glycans by supercritical fluid chromatography-mass spectrometry. AB - N-Linked glycans have been characterized by supercritical fluid chromatography (SFC) and SFC-MS using positive- and negative-ion chemical ionization. Four common oligosaccharide derivatives have been prepared and their chromatographic properties assessed on three SFC columns of varying polarity. Carbon dioxide has been used as the SFC mobile phase, with ammonia or CO2 added to the ion source for positive- and negative-ion chemical ionization, respectively. Direct SFC-MS interfacing allows the analytical manipulations of single-ion monitoring, total ion plots, background subtraction, library searches, and spectral reconstruction algorithms. Positive ammonia chemical ionization yields abundant molecular-weight information, (MH)+, and (MNH4)+ with little or no fragmentation. To capitalize on sensitivity, samples were prepared with the pentafluorobenzyl aminobenzoate reagent, acetylated, and analyzed by SFC-NICI-MS. This modification improves column efficiency and resolution and greatly enhances detecting sensitivity. These "soft" ionization conditions provide abundant molecular-weight-related anions for collision-induced dissociation and subpicogram detection. PMID- 1872471 TI - High-performance liquid chromatography assay for 3 beta-hydroxy-delta 5-C27 steroid oxidoreductase activity in rat liver microsomes. AB - A quantitative HPLC method has been developed for measuring 3 beta-hydroxy-delta 5-C27-steroid oxidoreductase activity in rat liver microsomes. Apparent Km values of 23 and 27 microM were estimated for 5-cholestene-3 beta,7 alpha-diol and NAD+, respectively. A temperature optimum of 45 degrees C was estimated using standard assay conditions. It was observed that feeding cholesterol (2%) or cholestyramine (5%) to rats increased (twofold) specific activity. This method should prove useful in studies of the regulation of bile acid synthesis and complement the HPLC assay technique recently developed for measuring cholesterol 7 alpha hydroxylase activity. PMID- 1872472 TI - Evaluation of assays for detecting alpha-1-protease inhibitor during purification from rat serum. AB - We purified the R1 alpha-1-protease inhibitor from rat serum and developed a convenient assay for its detection during purification procedures. Purification was accomplished by desalting, DEAE-Sephacel, zinc chelate, and reactive green agarose columns. The resultant antiprotease had a molecular weight of 54,000 and inhibited elastase, chymotrypsin, and trypsin. By isoelectric focusing, five bands were produced with pI values from 4.3 to 4.7. Functional assays utilizing protease substrates imbedded in agarose plates were evaluated for the ability to distinguish the R1 alpha-1-protease inhibitor from the other serum antiproteases eluted in column chromatography fractions. This technique of screening for anti protease activity was compared to conventional spectrophotometric methods and was found to correlate well when quantifying inhibition of elastase and chymotrypsin, but not trypsin. The presence of alpha-1-protease inhibitor was most reliably detected by testing for anti-elastase activity. Technician time and expense were saved by employing protease substrate plates to test chromatogrpahy fractions. This technique may facilitate purification of other protease inhibitors. PMID- 1872473 TI - Assay of HIV-1 proteinase: a colorimetric method using small peptide substrates. AB - A colorimetric assay for HIV proteinase using small protected peptide substrates is described. Substrates are cleaved to release N-terminal prolyl peptides which react with isatin to form a blue product which is measured spectrophotometrically. The assay is suitable for use with pure enzyme or crude extracts derived from genetically engineered Escherichia coli. PMID- 1872474 TI - Radiochemical assay of adenylosuccinase: demonstration of parallel loss of activity toward both adenylosuccinate and succinylaminoimidazole carboxamide ribotide in liver of patients with the enzyme defect. AB - A radiochemical assay for adenylosuccinase, an enzyme which intervenes twice in the biosynthesis of adenine nucleotides, has been developed. The two substrates of the enzyme, succinylaminoimidazole carboxamide ribotide (SAICAR) and adenylosuccinate (S-AMP), were synthesized in radioactive form by incubating [2,3 14C]fumarate and, respectively, AICAR and AMP with partially purified adenylosuccinase from yeast. Enzyme activities were determined by measuring the release of labeled fumarate after its separation from the substrate by chromatography on polyethyleneimine thin-layer plates. The ratio of the activity of adenylosuccinase measured with SAICAR compared to that with S-AMP was about 1 in crude extracts of rat liver and muscle and around 0.5 in human liver. In rat and human liver, but not in rat muscle, 20 to 40% of both activities of adenylosuccinase were lost after freezing at -80 degrees C followed by thawing. In the liver of patients with adenylosuccinase deficiency, in whom the deficiency had hitherto been measured only with S-AMP, the activity of the enzyme toward S AMP and SAICAR was found to be lost in parallel. This is in accordance with the finding that both SAICA-riboside and succinyladenosine accumulate in adenylosuccinase-deficient patients. PMID- 1872475 TI - On-sequencer pyridylethylation of cysteine residues after protection of amino groups by reaction with phenylisothiocyanate. AB - Cysteine residues in polypeptides are not easily identified during automated N terminal sequence analysis. Reaction of cysteine side chains with 4-vinylpyridine and identification as the pyridylethylated phenylthiohydantion derivative (PE-PTH Cys) were proposed. However, after this reaction a desalting step is necessary. If limited sample amounts do not allow this desalting step, on-sequencer pyridylethylation is an alternative, although preview of the consecutive amino acid is usually observed in this case. We describe an on-sequencer procedure that avoids such preview formation by derivatizing the peptide with phenylisothiocyanate (PITC) prior to reaction with 4-vinylpyridine. The pyridylethylation is performed in the cartridge of the sequencer after immobilization of the protein or peptide on a polybrene-coated glass fiber filter and thiocarbamylation with PITC. Preview caused by N-alkylation is not observed and PE-PTH-Cys is detected in much higher yields than usual. The procedure reported here is significantly shortened, optimized to reduce side products, and avoids losses during sample handling. It can easily be adapted to any automated version of the sequencers. PMID- 1872476 TI - Radiolabeling of the hydrophobic components of lung surfactant with 3 (trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine. AB - Studies of the metabolism and distribution of lung surfactant are aided by use of radiolabeled surfactant or surfactant components. These studies have often made use of [3H]- or [14C]phosphatidylcholine. Analysis of the lung content of surfactant containing these beta-emitting labels usually requires tissue digestion, use of scintillation fluids, and significant correction for quenching of photon production. Because use of a gamma-emitting isotope would obviate these requirements, we have investigated the use of 3-(trifluoromethyl)-3-(m [125I]iodophenyl)diazirine ([125I]TID), a lipophilic photoactivatable compound, to radiolabel pulmonary surfactant. Our results indicate that, during photoactivation, products of [125I]TID are produced that result in radiolabeling of both the lipid and protein components of extracted porcine surfactant. Separation of radiolabeled surfactant from hydrophobic nonlabelling photolysis products was accomplished by gel chromatography. Exposure of surfactant (34 mumol/ml) to [125I]TID under labeling conditions resulted in incorporation of 45.3 +/- 5.1% of the radiolabel. Incorporation of radiolabel in the various phospholipids of lung surfactant was approximately equivalent. Lipophilic surfactant apoproteins were also radiolabeled. Finally, both in vitro and in vivo testing of radiolabeled surfactant (0.1 microCi/mg) revealed full retention of surface tension lowering ability. PMID- 1872477 TI - Direct determination of phospholipid structures in microorganisms by fast atom bombardment triple quadrupole mass spectrometry. AB - When phospholipids ionized by fast atom bombardment undergo collisionally induced dissociation (CID), they cleave at specific bonds between the functional groups contained on the lipid. These cleavages are common to all classes of phospholipids. By taking advantage of this fact, a general scheme has been developed that uses a triple-quadrupole mass spectrometer to rapidly characterize the phospholipid content and structures present in crude lipid extracts. This scheme is based on fast atom bombardment ionization of a crude lipid extract and on the combination of positive-ion neutral-loss and parent scans and negative-ion daughter scans. Neutral-loss and parent scans provide independent diagnostic mass spectra for each of many specific phospholipid classes, while daughter scans provide the emperical formulas and positions of the fatty acyl constituents on each phospholipid. An automated tandem mass spectrometry (MS/MS) instrument can perform an extensive phospholipid screening on a single sample. A useful mass profile of the phosphatidylethanolamine species present in a 1-pg sample of mixed phospholipids (equivalent to ten Escherichia coli cells) has been obtained. The spectra are reproducible and proportional to concentration over at least the five logarithm range of cell concentrations studied. A rapid extraction procedure combined with the automated instrument control program produces profiles of the phospholipid classes, along with fatty acyl empirical formulas and position information, on selected phospholipid species, in a few minutes, from a single sample. PMID- 1872478 TI - Scanning tunneling microscopy and atomic force microscopy in the characterization of activated graphite electrodes. PMID- 1872479 TI - Electronic noses. PMID- 1872480 TI - Clinical chemistry. PMID- 1872481 TI - Water analysis. PMID- 1872482 TI - 1991-1992 Labguide. Scientific instruments, products, & services. PMID- 1872483 TI - Determination of urea in serum by using naturally immobilized urease in a flow injection conductimetric system. AB - A flow injection method was developed, aimed at the determination of urea in human serum. The system makes use of the naturally immobilized urease present in Canavalia ensiformis DC (jack bean). A column is filled with small pieces of this bean, and the sample (50 microliters) containing urea passes through it carried by a 1% NaCl solution. On leaving the column the stream is merged with an alkaline reagent (0.5 mol dm-3 NaOH; 0.5% disodium dihydrogen ethylenediaminetetraacetate). The ammonium ions, arising from the enzymatic reaction that occurs inside the column, are changed into the molecular form, which permeates a polytetrafluoroethylene membrane and is received in a de ionized water acceptor stream. The ammonia ionizes causing an increase in the conductance, which is proportional to the urea content of the sample. About 40 samples can be processed in 1 h with negligible carry-over and with a relative standard deviation of 1% or less. The results are in agreement with those obtained by a standard spectrophotometric method. PMID- 1872484 TI - Simultaneous determination of acetylsalicylic and salicylic acids in human serum and aspirin formulations by second-derivative synchronous fluorescence spectrometry. AB - A second-derivative synchronous scanning spectrofluorimetric method for the simultaneous determination of acetylsalicylic acid (ASA) and salicylic acid (SA) is described. The method is based on the native fluorescence of both acids in a 1% acetic acid-chloroform solution. Both ASA and SA can be determined within the concentration ranges 0.2-70 and 0.03-10 micrograms ml-1, respectively. The effect of each acid on the signal of the other has been studied in detail. Empirical equations have been used to overcome this effect, thus allowing the accurate determination of both acids in binary mixtures, without a separation step. The method has been applied to the determination of ASA and SA in blood serum and to the determination of SA impurities in aspirin formulations. Recoveries from sera spiked with both ASA (2.5-50 micrograms ml-1) and SA (100-160 micrograms ml-1) varied from 99.5 to 106.7% (mean = 102.6%) and from 93.0 to 98.0% (mean = 95.8%), respectively. Recoveries of SA from spiked aspirin solutions (0.25-1.5 mg g-1 of aspirin) varied from 98.0 to 102.0% (mean = 100.3%). PMID- 1872485 TI - Utility of certain pi-acceptors for the spectrophotometric determination of some penicillins. AB - Two simple and sensitive spectrophotometric methods are described for the determination of six penicillin derivatives. The methods are based on the reaction of these drugs as n-electron donors with either 2,3-dichloro-5,6-dicyano p-benzoquinone (DDQ) or 7,7,8,8-tetracyanoquinodimethane (TCNQ) as pi-acceptors, to give a highly coloured radical anion. The coloured products are quantified spectrophotometrically at 460 and 842 nm for DDQ and TCNQ, respectively. The optimization of the different experimental conditions is described. The interference from streptomycin sulphate and common degradation products was also studied. The proposed methods were applied successfully to the determination of the different penicillins investigated, either in pure or dosage forms, with good accuracy and precision. The results were compared with those given by the official United States Pharmacopeial XXI method. PMID- 1872486 TI - Spectrophotometric method for the determination of paraquat in water, grain and plant materials. AB - A sensitive spectrophotometric method for the determination of paraquat using ascorbic acid (an easily available reducing agent) is described. Paraquat is reduced with ascorbic acid in alkaline solution to give a blue radical ion with an absorbance maximum at 600 nm. Beer's law is obeyed in the range 12-96 micrograms of paraquat in 10 ml of the final solution (1.2-9.6 ppm). The important analytical parameters and the optimum reaction conditions were evaluated. The method was applied successfully to the determination of paraquat in water, grain and plant materials. PMID- 1872487 TI - Determination of nitrovin in medicated animal feeds by high-performance liquid chromatography. Analytical Methods Committee. AB - Nitrovin is extracted from a medicated feed by means of a solvent mixture consisting of dichloromethane, methanol and ammonia solution and then the nitrovin is determined in the extract by high-performance liquid chromatography using a cyano-column. PMID- 1872488 TI - Determination of vitamin E in animal feedingstuffs by high-performance liquid chromatography. Analytical Methods Committee. AB - A method is given for the determination of vitamin E in animal feeds and pet foods. The sample is saponified with ethanolic potassium hydroxide solution and the vitamin E extracted into light petroleum (boiling range 40-60 degrees C). This solution is evaporated to dryness under reduced pressure and the residue dissolved in hexane. The concentration of vitamin E in this solution is determined by high-performance liquid chromatography using a silica column and an isooctane-propan-2-ol mixture as the mobile phase. An alternative method using hexane-1,4-dioxane as the mobile phase is also given. PMID- 1872489 TI - Summaries of lectures presented at the 4th Literature Review Course for ABAI Examination. April 18-20, 1991, Chicago. PMID- 1872490 TI - Protruding atheromas in the thoracic aorta and systemic embolization. AB - OBJECTIVE: To determine whether protruding atheromas in the thoracic aorta are a risk factor for systemic embolization. DESIGN: Case-control study. SETTING: A referral hospital. PATIENTS: A total of 122 patients with a history of stroke, transient ischemic attack, or peripheral emboli and an equal number of age- and sex-matched control patients. MEASUREMENTS: Evaluation using transesophageal echocardiography was done in case patients to detect protruding atheromas in the thoracic aorta and in control patients for cardiac indications other than emboli. MAIN RESULTS: Matched logistic regression showed that the presence of protruding atheromas was strongly related to the occurrence of embolic symptoms (odds ratio, 3.2; 95% Cl, 1.6 to 6.5; P less than 0.001). Furthermore, atheromas with mobile components were present only in case patients. When known risk factors for stroke (hypertension and diabetes) were added to the model, the presence of protruding atheromas remained an independent risk factor for embolic symptoms (odds ratio, 3.8). Hypertension was also independently associated with embolic symptoms (odds ratio, 2.7), but diabetes was not (odds ratio, 1.0). CONCLUSION: Protruding atheromas in the thoracic aorta can be detected by transesophageal echocardiography and should be considered as a cause of strokes, transient ischemic attacks, and peripheral emboli. PMID- 1872491 TI - Predicting death in patients hospitalized for community-acquired pneumonia. AB - OBJECTIVE: To validate a previously reported discriminant rule for predicting mortality in adult patients with primary community-acquired pneumonia and to determine which factors available at hospital admission predict a fatal outcome among such patients. DESIGN: Historical cohort study. SETTING: University hospital. PATIENTS: Adults admitted to the hospital for community-acquired pneumonia. MEASUREMENTS: Using stepwise logistic regression, we analyzed prognostic factors (data available at admission and recorded in the medical record) that showed a univariate association with mortality. The predictive values of three discriminant rules were measured to validate the results of a previous study. MAIN RESULTS: Of 245 patients, 20 (8.2%) died. Of 42 prognostic factors identified in previous studies, 8 were associated with mortality, but only a respiratory rate of 30/min or more, a diastolic blood pressure of 60 mm Hg or less, and a blood urea nitrogen of more than 7 mmol/L remained predictive in the multivariate analysis. A discriminant rule composed of these three variables was 70% sensitive and 84% specific in predicting mortality, yielding an overall accuracy of 82%. CONCLUSION: Tachypnea, diastolic hypotension, and an elevated blood urea nitrogen were independently associated with death from pneumonia in our study, confirming the value of a previously reported discriminant rule from the British Thoracic Society. This rule may be useful in triage decisions because it identifies high-risk patients who may benefit from special medical attention. PMID- 1872492 TI - Pulse oximetry monitoring outside the intensive care unit: progress or problem? AB - OBJECTIVE: To evaluate the use of continuous pulse oximetry monitoring in general care units. DESIGN: Hemoglobin oxygen saturation data collected prospectively by use of pulse oximetry with concurrent review of the medical record. SETTING: General medical-surgical nursing units in a large, tertiary care university hospital. PATIENTS: Forty patients on two nursing units monitored with continuous, bedside pulse oximetry at the request of their primary physicians. MEASUREMENTS: All patients had continuous pulse oximetry monitoring. A research associate visited the bedside two or three times daily and recorded saturation compared with time data from the previous 8.75 hours. Patients were studied for 36 hours or until pulse oximetry monitoring was discontinued. Episodes of desaturation were counted. Patient charts were reviewed for documentation of desaturation in either nursing or physician notes. Orders adjusting oxygen therapy or other respiratory therapy within 12 hours of any desaturation episode were also recorded. MAIN RESULTS: Thirty of the 40 patients (75%) had at least one episode of desaturation to less than 90%; 23 (58%) had at least one episode to less than 85%. Desaturation episodes were documented in nursing notes for only 33% of those patients who desaturated to less than 90% and in physician notes in only 7% of cases. Changes in respiratory therapy were ordered in 20% of patients who desaturated to less than 90% and in only 26% who desaturated to less than 85%. CONCLUSIONS: Despite their repeated occurrence, episodes of hypoxemia were rarely documented in either nursing or physician notes. Further, even in patients who had episodic desaturation, pulse oximetry monitoring had little effect on changes in physician-directed respiratory care. PMID- 1872493 TI - Postmenopausal estrogen and prevention bias. PMID- 1872494 TI - The pathogenesis of sepsis. AB - Sepsis and its sequelae (sepsis syndrome and septic shock) are increasingly common and are still potentially lethal diagnoses. Many mediators of the pathogenesis of sepsis have recently been described. These include tumor necrosis factor alpha (TNF alpha), interleukins, platelet activating factor, leukotrienes, thromboxane A2, and activators of the complement cascade. Neutrophil and platelet activation may also play a role. Other agents that may participate in the sepsis cascade include adhesion molecules, kinins, thrombin, myocardial depressant substance, beta-endorphin, and heat shock proteins. Endothelium-derived relaxing factor and endothelin-1 are released from the endothelium and seem to exert a regulatory effect, counterbalancing each other. A central mediator of sepsis does not seem to exist, although TNF alpha has been commonly proposed for this role. Animal studies are difficult to extrapolate to the clinical setting because of cross-species differences and variations in experimental design. Rather than being caused by any single pathogenic mechanism, it is more likely that sepsis is related to the state of activation of the target cell, the nearby presence of other mediators, and the ability of the target cell to release other mediators. Also important is the downregulation or negative feedback of these mediators or the generation of natural inflammation inhibitors, such as interleukin-4 and interleukin-8. Endothelial damage in sepsis probably results from persistent and repetitive inflammatory insults. Eventually, these insults produce sufficient damage that downregulation can no longer occur; this leads to a state of metabolic anarchy in which the body can no longer control its own inflammatory response. PMID- 1872495 TI - The patient's story: integrating the patient- and physician-centered approaches to interviewing. AB - Patients produce biopsychosocial stories that integrate material from the medical and personal aspects of their lives. Capturing the personal aspect of the story requires that a patient-centered approach to clinical interviewing complement the equally important physician-centered approach. Patient-centered interviewing actively involves the patient and ensures that his or her perceptions, needs, and concerns are articulated during the physician-patient interaction. In our article, we define patient-centered interviewing and provide a rationale for using it. We also describe how patient-centered interviewing is done, how it is integrated with the physician-centered approach, and how to understand the product of this complementary approach to clinical interviewing, the patient's biopsychosocial story. PMID- 1872496 TI - Quality of care: do we care? AB - The quality of U.S. health care must improve. Practicing physicians need to become involved in generating new knowledge about what does and does not work in medical practice. Physicians might, for example, participate in building national databases on chronic and acute conditions using data from their patients or might help to enroll patients in cohort studies or experimental trials. Furthermore, our knowledge is now sufficient to support a substantial investment of funds in improving what physicians now do in medical practice and in developing publicly available standards of medical practice. Such standards or guidelines could be used by both physicians and patients as part of an explicit process to assess the medical appropriateness of expensive or dangerous procedures before they are done. In addition, the competence with which care is delivered also needs to be measured. Both of these assessments should be used prospectively by physicians to help patients choose the referral source that will maximize their preferences. PMID- 1872497 TI - Management of septic shock: present and future. PMID- 1872498 TI - Medicare payment reform: what are the prospects for internal medicine? PMID- 1872499 TI - Mycobacterium kansasii infection. PMID- 1872500 TI - Clinical trials and the elderly. PMID- 1872501 TI - Pentamidine prophylaxis of Pneumocystis carinii pneumonia. PMID- 1872502 TI - Transplants from the same donor. PMID- 1872503 TI - Walking reduces blood pressure. PMID- 1872504 TI - Effects of coffee in alcoholics. PMID- 1872505 TI - Extrapulmonary pneumocystosis. PMID- 1872506 TI - Akinetic mutism after baclofen. PMID- 1872508 TI - Lime disease. PMID- 1872507 TI - Case records and the classification of disease. PMID- 1872510 TI - Chlamydia trachomatis in the etiology of acute otitis media. AB - In an effort to show that Chlamydia trachomatis (CT) may be involved in the causation of acute otitis media (AOM), we performed three experiments. In the first, we inoculated the tympanic bullae of 6 chinchillas with CT. Five of the 6 inoculated animals developed CT AOM. In the second experiment, we sprayed the nasopharynx of 10 chinchillas with CT. Of these, 8 developed both pharyngitis and AOM, and in 6, live CT was cultured from the middle ear and pharynx. In the third experiment, 5 chinchillas had their conjunctiva inoculated with CT. Three developed CT conjunctivitis. Of these, 2 developed CT pharyngitis and 1 developed CT AOM. We concluded that CT will cause AOM in the chinchilla by direct inoculation into the middle ear as well as indirectly by infection of the nasopharynx and conjunctiva. PMID- 1872509 TI - Stapes surgery: complications and airway infection. AB - From a group of 1,111 patients who had stapedectomy or stapedotomy performed in a 10-year period, a thorough investigation was made of 11 patients who had a total hearing loss and 8 patients who developed a partial sensorineural hearing loss after operation. The data obtained indicate that postoperative infection with influenza virus may be responsible for unexpected complications following stapedectomy. A close relation was found between the appearance of complications and periods of epidemics of influenza. PMID- 1872511 TI - Familial sensorineural hearing loss: a correlative study of audiologic, radiographic, and vestibular findings. AB - A multidisciplinary approach to the study of a family with autosomal dominant sensorineural hearing loss is presented. The affected family members underwent extensive clinical and laboratory evaluation. They were found to have various degrees of bilateral congenital inner ear anomalies as imaged by computed tomography. The degree of structural abnormalities in the inner ears correlated with the severity of hearing impairment. Vestibular testing revealed nonspecific abnormalities generally correlating with audiologic and radiographic findings. This report presents a unique form of sensorineural hearing loss not previously described and is the first in-depth clinical study of nonsyndromal "Mondini dysplasia" occurring in a family. PMID- 1872512 TI - Tetanic response of the cricothyroid muscle. AB - Tetanic response of canine cricothyroid muscle tissue was investigated through a series of experiments conducted in vitro. Two separate portions of the cricothyroid muscle, namely the pars recta and pars oblique, were studied. Samples of the muscle were dissected from dog larynges excised a few minutes before death and kept in Krebs-Ringer solution at a temperature of 37 degrees +/- 1 degrees C and a pH of 7.4 +/- 0.05. Tetanic contraction of the muscle samples was obtained by field stimulation to the muscle through a pair of parallel-plate platinum electrodes and with a train of square pulses of 0.1-millisecond duration and 85-V amplitude. Isometric force responses of the pars recta and pars oblique muscles were obtained electronically with a dual servo system (ergometer). The effect of tissue elongation on the active and passive responses was quantified by stimulation of the sample during cyclic elongation. Both active and passive responses as a function of elongation were obtained on the same sample. PMID- 1872513 TI - Distribution of immunocompetent cells in normal nasal mucosa: comparisons among germ-free, specific pathogen-free, and conventional mice. AB - To better understand the role of immunocompetent cells in the defense mechanism of the upper respiratory tract against microbial invasions, the distribution patterns of those cells were investigated in nasal mucosa of mice maintained in three different conditions: germ-free (GF), specific pathogen-free (SPF), and conventional (CV) conditions. Immunostaining by the indirect peroxidase method and toluidine blue staining were employed for the detection of immunocompetent cells and mast cells. For immunostaining, anti-IgG, -IgA, and -IgM polyclonal antibodies and anti-Lyt-1, -Lyt-2, and -Mac-1 monoclonal antibodies were used as primary antibodies. In nasal mucosa of CV mice, Mac-1+ cells, mast cells, and all cell types of lymphocyte subsets were present. In nasal mucosa of SPF mice, all cell types were also positive, but fewer in number than those of CV mice. In nasal mucosa of GF mice, IgG+, IgA+, and Lyt-2+ cells were rare, although IgM+ and Lyt-1+ cells were present in small numbers. An electron microscopic study revealed that follicle-like lymphocyte aggregates with high endothelial venules were present in nasal mucosa close to the mucosal epithelia. These findings suggest that lymphocytes are mobilized to nasal mucosa, responding to continuous antigenic stimuli, and play an important role in the local defense mechanism of the upper respiratory tract. PMID- 1872514 TI - Apron tracheostome. AB - Stenosis of the tracheostome following total laryngectomy is not an infrequent complication, either immediately postoperatively or years later, and it poses a common problem for head and neck surgeons. The opening becomes inadequate and the patient is uncomfortable and panicky. A secondary plastic operation is necessary in order to improve the airway, or a laryngectomy tube must be worn constantly. I have developed a satisfactory technique for tailoring the tracheostome during total laryngectomy so as to minimize postoperative stenosis even in irradiated cases and allow the patient to dispense with the laryngectomy tube. It may render the posterosuperior wall of the tracheostome more suitable for a tracheoesophageal puncture tract for voice restoration after total laryngectomy. These goals are achieved by interdigitating a small skin-thick superiorly based apron flap, raised from the lower midline of the front of the neck, into a similar recipient area at the upper posterior tracheal wall after removal of an equal mucosal apron. PMID- 1872515 TI - Zinc in the management of tinnitus. Placebo-controlled trial. AB - To assess any possible beneficial effect from zinc on tinnitus we performed a placebo-controlled, randomized, double-blind investigation. Forty-eight patients with tinnitus were randomized to either placebo or the administration of zinc sulfate as sustained-release tablets of 22 mg Zn++ (Zinklet). The tablets were administered three times daily for 8 weeks. Every week the patients stated the severity of tinnitus on a number scale from 0 to 10. The levels of zinc and albumin in serum were determined both before and after treatment. Of 48 patients with tinnitus, hypozincemia was found in only one patient. The zinc level increased significantly in the patients treated with zinc. We could not demonstrate any beneficial effect from zinc on tinnitus. One of the essential reasons for this finding could be that the zinc levels in serum were in the normal range previous to treatment. PMID- 1872516 TI - Ultrastructure of cat superior vestibular commissural neurons. AB - The ultrastructure of the feline superior vestibular commissural neurons (CNs) was studied after labeling by contralateral injection of horseradish peroxidase. These small spindle-shaped cells are found in clusters oriented in a rostrocaudal, dorsoventral or lateromedial direction. The CNs have a cleft nucleus, with the majority of nerve terminals contacting the CN near the emergence of polar dendrites. Polarization of the afferent synaptic profiles suggests a bidirectional nature of inputs to CNs by the vestibular nerve, contralateral CNs, and/or cerebellar systems. One type of labeled cell does not conform to this pattern, instead resembling a vestibulo-ocular neuron. Hence, it may function as a commissural and a vestibulo-ocular neuron. Characterization of different types of synapses, based on the size and eccentricity of their synaptic vesicles, indicates a continuum rather than separate populations. Volume fraction of intracellular organelles showed a larger volume fraction percent of polyribosomes in larger cells. Since this organelle is involved with protein synthesis, this finding may indicate that larger CNs have a more extensive dendritic tree. PMID- 1872517 TI - Pressure chamber tympanometry in diving candidates. AB - The currently recommended examination for diving fitness ascertains middle ear autoinflation ability only under surface pressure conditions. The purpose of our study was to document and quantify middle ear pressure equalization failure during simulated dives among diving candidates who had otherwise met the otologic criteria for diving fitness. Forty-two candidates for regular naval diving activity were included in the study. Tympanograms of both ears at 1 and 1.1 absolute atmospheres (ATA) were taken inside a pressure chamber with the subjects in two positions: seated and supine. At a pressure of 1 ATA, type A tympanograms were found in all 84 ears examined. At a pressure of 1.1 ATA, with subjects in the upright position, 19 (22.9%) of the ears had type C and 2 (2.4%) type B tympanograms, while with subjects recumbent during descent, 6 of the ears (7.2%) had type C and 7 (8.4%) type B. Our results suggest that successful autoinflation at surface ambient pressure does not necessarily reflect middle ear pressure equalization ability during descent in a dive. PMID- 1872518 TI - Choanal atresia and lymphedema. AB - The coexistence of bilateral bony choanal atresia and lower-extremity lymphedema was observed in a family with several consanguineous marriages. The combination of these two rare anomalies, in a hereditary form, has not been described before. PMID- 1872519 TI - Regulation of phonatory efficiency by vocal fold tension and glottic width in the excised canine larynx. AB - An excised canine larynx was used to assess the effects of glottic width and vocal fold tension on acoustic power, aerodynamic power, and vocal efficiency. Multiple regression analysis of the data obtained from 10 larynges revealed that with increased vocal fold tension there is a logarithmic decline in radiated acoustic power, while aerodynamic power remains constant (p less than .05). Vocal efficiency has a similar logarithmic decrease with increased tension (p less than .05). With narrowing of the glottis, the acoustic power increases more than the aerodynamic power delivered to the larynx, and the efficiency increases. The inverse relationships glottic width has with acoustic power and vocal efficiency are best described by a reciprocal model (p less than .01). There is a negative linear relationship between glottic width and aerodynamic power. These results suggest that within the larynx the energy conversion is regulated by glottic aperture and longitudinal vocal fold tension. The optimal width for efficiency appears to be the narrowest width that produces phonation within the modal register, whereas increased tension decreases the efficiency of the glottis. PMID- 1872520 TI - Endoscopic and videofluoroscopic evaluations of swallowing and aspiration. AB - A new procedure for evaluating oropharyngeal dysphagia utilizing fiberoptic laryngoscopy was compared to the videofluoroscopy procedure. Twenty-one subjects were given both examinations within a 48-hour period. Results of the fiberoptic endoscopic evaluation of swallowing (FEES) and videofluoroscopy examinations were compared for presence or absence of abnormal events. Good agreement was found, especially for the finding of aspiration (90% agreement). The FEES was then measured against the videofluoroscopy study for sensitivity, specificity, positive predictive value, and negative predictive value. Sensitivity was 0.88 or greater for three of the four parameters measured. Specificity was lower overall, but was still 0.92 for detection of aspiration. It was concluded that the FEES is a valid and valuable tool for evaluating oropharyngeal dysphagia. Some specific patients and conditions that lend themselves to this procedure are discussed. PMID- 1872521 TI - Septic jugular thrombosis with abscess formation. PMID- 1872522 TI - Basaloid monomorphic adenomas. AB - Monomorphic adenomas can be divided into basaloid and nonbasaloid type. With the exception of the canalicular adenoma, the basaloid monomorphic adenomas are preponderantly tumors of the major salivary glands, most often the parotid gland. The dermal analogue monomorphic adenomas, so named because of their histologic similarity to eccrine tumors of the skin, are a unique subset of the basaloid adenomas. They are often multifocal, recur frequently, may undergo malignant change, and can be part of a salivary-cutaneous tumor diathesis. PMID- 1872523 TI - [Childhood accidents caused by farming machines in France. Epidemiology, consequences, prevention]. AB - As part of the actions led by the French Center for Information and Encounters for the Prevention of Childhood Injuries, a recent meeting on childhood injuries caused by farming machinery was held recently. These injuries are not exceptional in view of the steadily diminishing number of children living on farms. They are often severe, with several deaths each year in France and devastating sequelae in other cases. Prevention requires improved safety of these machines to which farmers' children are exposed in their everyday life, as well as information efforts targeted to the highest risk populations, i.e., boys in specific age groups and specific regions. Such a program can be implemented only with the cooperation of involved industries, insurance companies and official agencies, as part of a long-term, decentralized policy. PMID- 1872524 TI - [Emergency medical care and severe home accidents in children. Study of 630 cases over 5 years. Their significance in traumatic accidents]. AB - Among calls put through to the Mobile Emergency Unit of a Paris urban area district for a pediatric problem over a five-year period (n = 630), 19% were for a household injury (with or without physical injury) and 22% (n = 712) were for a physical injury outside the home. Thus, injuries were the reason for over 40% of pediatric calls and half these injuries occurred in the child's home. Household injuries were serious, with a prehospital mortality rate of nearly 5% and intensive care treatment in one-third of cases. Fifty-five per cent (60% in boys) of household injuries occurred in preschool-age children. Half these injuries (burns excluded) were physical injuries (66% in boys). Forty per cent of household injuries (n = 251) were caused by a fall, from over one meter in half the cases. Most of these injuries occurred around mealtimes (3/4 of cases). As compared with out-of-home childhood injuries, prehospital mortality rate was significantly higher (p less than 0.001) and single injuries significantly more prevalent (p less than 0,001) in household physical injuries. Prevalences of lesions of the face, head and neck, chest, abdomen, and pelvis were comparable for out-of-home and at-home physical injuries; conversely, lesions of the upper limbs were more common in household injuries (p less than 0,01), whereas lesions of the lower limbs were more prevalent in out-of-home trauma. Lastly, household physical injuries occurred mainly in children under five, whereas out-of-home childhood injuries were more common after five years of age (p less than 0,001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872525 TI - [Reactive arthritis caused by Yersinia in children. Report of 4 cases]. AB - Among a group of children hospitalized for "joint pain", four of the cases of reactive arthritis were due to Yersinia infection. These four cases are described. Some patients had suggestive clinical symptoms but serologic studies were needed to establish the diagnosis. Tissue group studies showed that two children were HLA B27 and one was HLA B7. Reactive arthritis due to Yersinia in a form of "enteral arthritis". The prevalence of Yersinia arthritis has not been documented. Serologic tests are essential to outrule the main differential diagnosis, i.e. chronic juvenile arthritis (juvenile rheumatoid arthritis). Short term resolution of symptoms is seen in every case. The long-term outcome is less well documented, especially with regard to the risk of recurrence and to relationships with peripheral joint disease and spondylarthropathies of early adulthood. HLA B27 positivity may be a risk factor. The pathogenesis of Yersinia induced reactive arthritis is unclear; current studies are focusing on immunologic factors. The uncertainties concerning long-term outcome justifies renewed interest in childhood reactive arthritis. PMID- 1872526 TI - [Morbidity and psychomotor development at 2 years of age in children born in Puy de-Dome in 1983. Study of children groups defined by perinatal risk]. AB - All infants born in the Puy-de-Dome area in 1983 and referred to a neonatal care unit were studied prospectively. Children were seen at their homes at 9 months and at 2 years of age and results were compared with those found in controls. High risk groups were defined on the basis of neonatal variables including prematurity, neurologic anomalies, respiratory distress, assisted ventilation, and growth retardation. At birth, prematurity was associated with an increased risk of respiratory distress and infections were more common in small-for-dates infants. Evaluations at 9 months and at 2 years of age showed increased prevalences of growth retardation and strabismus in the high-risk infants, and neurodevelopmental tests disclosed lower performances in these children. Conversely, infectious diseases and readmissions between birth and two years of age were not increased in the high risk groups, as compared with the control group. PMID- 1872527 TI - [Behavior of Clostridium perfringens in the intestine of newborn infants born by cesarean section]. AB - Colonization of the digestive tract by C. perfringens was studied in infants born by cesarean section. Correlations between the level of colonization and the environment, type of feeding, and presence of other anaerobic bacteria were looked for. Colonization by C. perfringens was found as early as the second day of life in one of the maternity wards studied, suggesting presence of the microorganism in the environment. By the 14th day of life, colonization with C. perfringens was demonstrated in all the bottle-fed or breast and bottle-fed infants. In strictly breast-fed infants, findings suggested antagonism between Bifidobacterium and C. perfringens. Bacteroides and Clostridium species other than C. perfringens were not found prior to colonization by C. perfringens. PMID- 1872528 TI - [Varicocele in children and adolescents. Review of a series of 58 cases]. AB - 5 to 25% of male adolescents present with a varicocele; only those cases inducing serious discomfort or affecting the development of the testis require surgical treatment. Nevertheless, the results of surgery are disappointing, with a high recurrence rate. Based on a better knowledge of testicular venous drainage, it appears that conventional high ligation of the spermatic vein (s) might not be sufficient to cure varicocele. Fifty-eight patients were operated upon using four different procedures. Only complete, proximal ligation of all of the visibly dilated veins seems to prevent recurrences with a follow-up of at least one year. However, out of eleven cases treated with this original procedure, one patient, already operated upon twice without success, developed secondary atrophy. PMID- 1872529 TI - [Renal agenesis, bicornuate uterus and cyst of the Gartner's duct]. AB - A cyst of Gartner's duct with a bicornuate, unicervical uterus and ipsilateral renal agenesis were seen in a 13-month-old girl. Left renal agenesis had been suggested by antenatal ultrasound findings. After birth, there were no symptoms but ultrasonography demonstrated a multicystic mass in the pelvis. Diagnosis was confirmed by histological study of the mass which had been completely removed during surgery. This infrequent genitourinary malformation is due to a developmental abnormality of the wolffian duct early in fetal life. This case is the eighth report in the literature. Course can be complicated by abscess formation and malignant transformation but most patients remain symptom-free. Treatment is discussed. PMID- 1872530 TI - [Recurrent multifocal periostosis in children. Report of a familial form]. AB - Recurrent multifocal periostosis of childhood is an infrequent disease. All cases reported to date have been sporadic. A familial form affecting three siblings is reported herein. Clinical and biologic features were similar to those described in the previously reported cases. This case is of particular interest for two reasons: 1) the pattern of familial clustering suggests autosomal recessive transmission; 2) repeated CT scans were performed in these patients (but not in previously reported cases) and demonstrated early involvement of the three bone layers, suggesting panostosis rather than periostosis. PMID- 1872531 TI - [4p trisomy secondary to paternal translocation t(4p-;15q+)]. AB - A new case of trisomy 4p is reported. The patient was a boy with dysmorphism, growth failure and developmental retardation. Craniofacial features included microcephaly with a flat forehead, a prominent glabella, hyperteleorism, a broad, concave nasal bridge, a bulb-shaped nose, a wide mouth with a prominent upper lip and a short philtrum, low-set ears, a low hairline, micrognathia, and a short neck. Abdominal muscles were normal. Cryptorchidism with a hypoplastic scrotum and a micropenis were found, as well as forced flexion of the fingers and talipes equinus. The intravenous urogram disclosed ptosis of the right kidney. Developmental retardation was severe with an IQ under 50. RHG banding techniques on peripheral lymphocytes disclosed 4p14 pter duplication. The karyotype was 46,XY inv dup(4-p) (p14----pter). The mother's karyotype was normal. The father had a translocation between the short arm of chromosome 4 and the long arm of chromosome 15; his karyotype was 46,XY, t(4;15) (p14;q26). Thus, the child had trisomy for a segment of the short arm of chromosome 4 (p14----pter) and monosomy for the terminal band of the long arm of chromosome 15 (15q26). The first case of trisomy 4p was reported in 1970 by Wilson et al. Since then, there have been 46 additional reports in the medical literature. Although children with trisomy 4p share a number of features, the phenotypic manifestations of this chromosomal abnormality are variable and nonspecific, making clinical diagnosis difficult. PMID- 1872532 TI - [A case of esophageal duplication discovered in a newborn]. AB - A case of esophageal duplication discovered in the neonatal period is reported and discussed. This infrequent malformation (9% of all childhood mediastinal tumors) is an entoblastic duplication of the digestive tract and is often accompanied with spinal malformations. The duplication may be either cystic or tubular; the latter form usually opens into the normal esophagus. The most common clinical manifestations are respiratory symptoms caused by compression. The diagnosis, suggested by the findings on the plain chest film and osephageal opacification, is confirmed by the ultrasound examination and, above all, the CT scan. The treatment of this malformation is surgical. Reconstruction may be difficult but overall results and prognosis are excellent. PMID- 1872533 TI - [Hemiballism. Description of a clinical case in childhood]. AB - Biballism is an infrequent hyperkinetic disorder characterized by involuntary, intermittent, violent, uncontrollable contractions of the proximal muscles of the limbs. Biballism is classically ascribed to a lesion in the controlateral subthalamic nucleus or its connections but other causes have been reported. These include infections (bacterial, viral parasitic), cerebrovascular lesions, tumors, toxics, and systemic disease (systemic lupus erythematosus). Although poorly understood, the pathophysiology of hemiballism is widely believed to involve hyperactivity of the dopaminergic system. The prognosis of these abnormal movements, formerly poor, has been improved by the use of neuroleptics and drugs acting on the different neurotransmitter systems. A unique case of biballism at resolution of a febrile coma in a 4 1/2 year old is reported. The EEG showed diffuse slow waves. A hyperdense lesion was visible in the right thalamic region on the cerebral CT scan. The magnitude of the abnormal movements decreased under haloperidol. The etiology of this case of biballism is discussed. PMID- 1872534 TI - Team approach to total auricular reconstruction. AB - The surgery of microtia is a procedure that demands surgical and artistic skills, as well as precise planning of interventions. In cases where a functioning inner ear is present, functional and esthetic reconstruction is performed jointly with ear, nose, and throat surgeons. The middle ear plasty is performed through a transmastoidial approach at the time of the second stage of the outer ear reconstruction. We demonstrate the special requirements of this team approach and also pay a tribute to Burt Brent, who has set the standards of modern ear reconstruction. PMID- 1872535 TI - The sensory tensor fasciae latae flap: a 9-year follow-up. AB - From January 1979 to April 1989, 19 neurosensory tensor fasciae latae flaps were used to cover ischial pressure sores in paraplegic patients. This flap provides protective sensation and improves the sensory control of the filling status of the rectum and the sitting control in a wheelchair. Patients were reexamined between 12 and 110 months; no recurrence or new pressure sores were seen. Indications, early and late complications, and evolution of the sensation are discussed. PMID- 1872536 TI - Why the denervated gastrocnemius muscle flap should be encouraged. AB - The superiorly based, denervated gastrocnemius muscle flap is able to perform an aesthetically excellent and functionally good cover for defects of the upper one third of the calf, including the knee, and the lower one-third of the thigh. A consecutive series of 41 muscle and musculocutaneous gastrocnemius flaps was analyzed. Thirty-six patients (88% of the patients who underwent surgery) could be reexamined. The mean follow-up time was 36 months, with a minimum time of 12 months. At the time of examination, all skin defects as well as the incidental concomitant osteomyelitis had completely healed; however, 40% of the patients have required secondary operations. One-half of the patients have a functional deficiency, and 20% showed areas with loss of sensation. After surgery with musculocutaneous flaps, all patients complained about the sensory loss of the saphenous nerve, and peripheral edema was seen more often than after surgery with a simple muscle flap. Muscle flaps with residual innervation showed more secondary wound breakdown and more contraction pain, due to spasms. The best results concerning function and aesthetics are achieved with denervated muscle flaps covered by a split-thickness skin graft. In this variation, the flap showed good and stable coverage without bulk, as well as minimal donor-site deformity; therefore, primary denervation must be considered. The anatomy of the motor nerves to the gastrocnemius muscle is shown. PMID- 1872537 TI - Sensibility and cutaneous reinnervation after breast reconstruction with musculocutaneous flaps. AB - Sensibility and sensory reinnervation were investigated in 19 patients who underwent, after mastectomy, a breast reconstruction using myocutaneous flaps. A comparative study in reinnervation of the flaps has been performed either after surgery with a latissimus dorsi flap with prosthesis or after surgery with a simple or double pedicle transverse rectus abdominal flap. Ten patients with latissimus dorsi flaps and 9 patients with transverse rectus abdominal flaps were tested. The tests included stimulation with touch, pressure, pin prick, and temperature. The patients were also interviewed regarding their impressions, a subjective sensibility. These results show that the recovery of sensibility by patients who underwent surgery with the transverse rectus abdominal flap technique is superior, objectively and subjectively. PMID- 1872538 TI - Evaluation of long-term results in breast reconstruction using the latissimus dorsi flap. AB - To evaluate the early and long-term results of the latissimus dorsi musculocutaneous flap for breast reconstruction, a series of 92 women who underwent surgery at my department from 1979 to 1989 was critically reviewed. Special attention was directed to the late foreign body reactions leading to deformation, asymmetry, and induration of the reconstructed breast. Guidelines regarding prevention of capsular contraction are discussed and some essential surgical refinements outlined. PMID- 1872539 TI - Microsurgical free toe pulp transfer for digital reconstruction. AB - Posttraumatic fingertip reconstruction with a free toe pulp neurovascular flap, first described in 1979, has not been frequently reported. We present our results with 8 free transfers of the toe pulp and demonstrate the successful restoration of a well-padded and sensitive fingertip. All patients, studied with a follow-up of up to 20 months, recovered a discriminative sensibility of the thumb and main fingers, with a stationary two-point discrimination test between 5 and 12 mm and a moving two-point discrimination test between 4 and 8 mm. In spite of the good results obtained, we believe this procedure must be chosen only in certain circumstances. We present the indications and the contraindications for this digital reconstruction. PMID- 1872540 TI - Aesthetic units in skin grafting of the face. AB - In patients with difficult facial reconstructions, one of the most important requirements is to plan well, before beginning treatment. It is known that it is important to consider the aesthetic unit of the face. Each cutaneous area is to be reconstructed by a single, separate graft or flap. We present 4 patients illustrating difficult situations. Special attention has been drawn to the choices for each separate graft or flap. This study was made possible with the aid of a medical illustrator who prepared a real dissection of our final reconstruction. In fact, after these difficult operations, we often forget exactly what was previously done and we believe that a good catamnesis of our surgical adventure can be useful to share with other surgeons who deal with the same difficult procedures. PMID- 1872541 TI - Extrinsic eyelid ectropion. AB - Extrinsic ectropion is caused by loss of skin around the orbital margins. Every patient with cicatricial ectropion should be assessed thoroughly to determine if the cause is intrinsic, extrinsic, or both. This assessment is extremely important when dealing with severe deformities after burns, cancer, or noma, for example. The assessment allows a proper planning of surgery. As a rule, the original size and location of the missing tissues should be recreated and the defect replaced by homologous tissues. PMID- 1872542 TI - Total anterior tenoarthrolysis to treat inveterate flexion contraction of the fingers: a series of 16 patients. AB - Total anterior tenoarthrolysis was originally described by Saffar to treat flexion contractions of the fingers. This procedure consists of releasing the entire flexor apparatus and the interphalangeal volar plates through a lateral incision and a volar subperiosteal dissection. The anterior flap slides proximally in relation to the bone, leaving a pulpar defect. To maintain the digital pulp intact, we proposed advancing the volar flap and transposing the defect at the base of the finger. A series of 16 patients who underwent total anterior tenoarthrolysis are presented; 6 patients underwent surgery according to our modification. Postoperative range of motion was improved in 11 of 16 patients and correlated with subjective patient appreciation. Fingers that had a preoperative interphalangel total active motion greater than 55 degrees were significantly improved. No improvement was seen among patients with stiff, crooked fingers. The average total extension deficit decreased from 33 degrees at the proximal interphalangeal joint level and 6 degrees at the distal interphalangeal joint level. Total anterior tenoarthrolysis is considered a salvage procedure to treat flexion contractures of the fingers with articular cartilages that are in good condition and tendons that are still working. PMID- 1872543 TI - Histomorphometric studies in patients with facial palsy treated by functional muscle transplantation: new aspects for the surgical concept. AB - Whenever it was possible, muscle and nerve biopsies were performed in patients with irreversible, unilateral facial palsy treated by cross-face nerve grafting and free gracilis muscle transplantation with microneurovascular anastomoses. Planimetric analyses of cross-sections showed the following, to some extent, surprising, results: (1) Independent of the final functional result, approximately the same number of regenerated, thin nerve fibers (100-200) were found in the distal end of the cross-face nerve graft at the time of muscle transplantation. These are approximately 20% of the nerve fibers counted in the branches of the facial nerve at the healthy side used for reinnervation. (2) There is no correlation between the number or diameter of the nerve fibers in the distal end of the cross-face nerve graft and the functional recovery of the transplanted muscle, but there is good correlation between the morphology of the fibers of the muscle graft and the functional result. (3) Different portions of slow-contracting and fast-contracting muscle fibers in the reinnervated muscle grafts showed the strong influence of the quality of the nerve used for the crossover innervation. If a facial nerve branch innervating the slow buccinator muscle was used, the originally fast gracilis muscle was transformed to a slow muscle by this kind of reinnervation. These important findings are the basis of a new view of surgery in the treatment of irreversible facial palsy by functional free-muscle transplantation. PMID- 1872544 TI - Tissue expanders in reconstruction of burn sequelae. AB - In 20 patients with burn scars and 1 patient with a fresh burn, 33 tissue expanders were implanted. In 16 patients, the expansion fulfilled the goal set with the help of 27 expanders. The results are very satisfactory, but the effort of treatment and the trouble are substantial. Thirteen patients encountered no complications. In terms of expanders, there were 6 major and 11 minor complications. They were infection (three), wound dehiscence (two), insufficient expansion with hematoma (one), leakage (six), superficial skin damage (three), and intercurrent hematoma formation (two). There was no flap necrosis, and thus, apart from superfluous surgery, no real damage. Retrospectively, the major complications could have been avoided by more careful observance of indications. Unfortunately, this seems to be a process that every surgeon must learn by experience and not by theory alone. Here, infection was managed by removal of the expanders. Hematomas should be evacuated early (we drained most expanders), and incidences of leakage can be diminished by using larger valves. Small incisions in healthy tissue for expander insertion may lead to faster onset of expansion, thus, shortening the procedure. Late widening of scars was found only once, perhaps due to a rather long duration of expansion, averaging 13 weeks. PMID- 1872545 TI - Lipoplasty of the abdomen and lateral thighs. AB - Liposuction, today, has become a routine technique for plastic surgeons and is frequently also used by nonspecialists. To obtain the best results, it is necessary to follow more rigorous standards of patient selection with a technique that is safely performed in the best possible way. The patients' expectations must be realistic and carefully considered. I try to demonstrate with illustrations that, by respecting these norms, the preoperative objectives set by the surgeon and the patient can be regularly reached. PMID- 1872546 TI - Spontaneous regression of metastatic melanoma. AB - Spontaneous regression of malignant melanoma is a well-known but rare event. It seems to be caused by immunological enhancement similar to the regression observed after intralesional injection of Bacille Calmette-Guerin into cutaneous melanoma metastases. A patient is presented in whom an incisional biopsy of a metastatic melanoma in an inguinal lymph node was followed by complete disappearance of the metastasis. Reviewing the literature, several similar patients were found in whom spontaneous regression of a metastatic melanoma occurred after an incomplete excision or biopsy of the tumor. It appears that in rare instances, an unspecific mechanical stimulus may trigger an increase in immunocompetence, although laboratory evidence for this has only rarely been produced. A plea is made for serial immunological studies in consecutive patients with melanoma, to further elucidate these puzzling phenomena. PMID- 1872547 TI - Otoplasty without a conformer dressing. AB - Since 1969, all our constructive, reconstructive, and aesthetic otoplasties have been managed without a conformer dressing. U-sutures, loosely tied over coated cotton rolls up until 1975, when thin and elastic silicone tubes began to be used, maintain the tissues in their new position. Experience and results of 193 ear operations are reported. PMID- 1872548 TI - Microsurgical reconstruction: experience with free fascia flaps. AB - Microsurgical reconstruction can often benefit from the thin, pliable, and vascular characteristics of free fascia flaps. Investigation to identify donor sites and to maximize reliability of these flaps continues. Microfil injections of the thoracodorsal artery confirm the ability to use the fascia overlying the serratus anterior muscle as a free flap based on this vessel. We have used this flap in distal extremity wounds in 4 patients with one failure (venous thrombosis). Free fascia flaps from other donor sites have been used in 9 patients in a variety of locations (head and neck, hand, and extremity) with excellent results. We conclude that when thin, well-vascularized tissue is required for reconstructive purposes, the skin-grafted free fascial flap provides excellent durable coverage with minimal donor site complications. PMID- 1872549 TI - Recontouring of the lateral forehead using the temporalis muscle. AB - Contour deformities of the lateral forehead are not uncommon after direct injuries or extirpative procedures, or as a sequela to iatrogenic maneuvers for juxtaposed craniomaxillofacial endeavors. Transposition of noncutaneous local vascularized autogenous tissues for augmentation of these defects has minimal inherent risks and little donor site morbidity. Although the temporoparietal fascia has previously been described as a first choice in this regard, if unavailable due to concomitant injury or absence of the superficial temporal vessels, the temporalis muscle itself provides an excellent second option that deserves consideration. PMID- 1872550 TI - Nineteen years' experience with polyurethane foam-covered mammary prosthesis: a preliminary report. AB - Long-term reviews of patients undergoing augmentation mammaplasty seem to be rare. Recently, a long-term study of patients who had undergone augmentation with polyurethane foam-covered prostheses was undertaken. However, at the time that study was published, the longest follow-up was just over 4 years. We have been using the polyurethane-coated prosthesis almost exclusively for nearly 20 years. The procedure is performed by one surgeon using a consistent technique, and all implantations were retroglandular. In reviewing this series, a follow-up rate of nearly 60% was achieved in patients augmented for periods of 1 to 19 years. The length of this study, together with a high follow-up compliance rate, makes this an unusual contribution to the literature on augmentation mammaplasty. PMID- 1872551 TI - Effects of hyperbaric oxygen preservation on rat limb replantation: a preliminary report. AB - The effect of hyperbaric oxygen, administered during storage, on the survival of replanted limbs was evaluated in rats. The right hindlimbs of male Sprague-Dawley rats were severed and were replanted by microvascular anastomoses after storage in either room air or hyperbaric oxygen (100% oxygen at 2.9 atm absolute) at 23 degrees C for 5 hours. The administration of hyperbaric oxygen during storage improved limb survival from 50% in the room-air, control rats to 100% (p less than 0.05). The gastrocnemius muscle of limbs treated with hyperbaric oxygen demonstrated a higher level of energy reserves (creatine phosphate, adenosine triphosphate, glycogen, and glucose) than the same muscle in room-air, control rats. The mechanisms of the beneficial effect of hyperbaric oxygen on limb survival appears to be related to preservation of high-energy phosphates and glycogen. PMID- 1872552 TI - Microfixation techniques in pediatric craniomaxillofacial surgery. AB - Microfixation represents a technical advance that has been developed for the specific needs of the infantile and pediatric craniomaxillofacial skeleton. The microplates provide significant skeletal stability despite their size and are relatively easy to apply and adjust after placement. The advantages and the technical aspects of microfixation use versus those of minifixation in smaller skeletal structures are presented. The range of applications in pediatric craniofacial surgery is demonstrated and reviewed in our series of 65 children, with a greater than 1-year follow-up. PMID- 1872553 TI - The great auricular nerve revisited: pertinent anatomy for SMAS-platysma rhytidectomy. AB - Aesthetic platysma surgery during rhytidectomy has gained popularity for contour restoration of the jaw line, cervicomental angle, as well as anterior neck defects. The superficial musculoaponeurotic system-platysma flap is elevated and suspended in a cephaloposterior direction by suturing to the investing fascia overlying the sternocleidomastoid muscle and the mastoid bone. This procedure is usually performed without total visualization of the great auricular nerve, possibly placing this nerve at risk during suspension. Anatomical dissections of the great auricular nerve were performed bilaterally on 10 cadavers to delineate its course in the superior neck and identify anatomy pertinent to the elevation of flaps and placement of sutures during superficial musculoaponeurotic system platysma suspension. PMID- 1872554 TI - Soft-tissue blood flow after segmental osteotomy of the canine tibia. AB - The response of soft-tissue blood flow to a segmental osteotomy of the canine tibial diaphysis was investigated. Forty-three dogs underwent unilateral tibial osteotomies to create a 2.5-cm avascular diaphyseal segment, which was then rigidly stabilized with a plate. Blood flow measurements of the limbs that underwent surgery and control limbs were made using cerium 141 microspheres. One month after surgery, blood flow to the caudal musculature was increased 1.4-fold and at 2 and 3 months was twofold the value of the control side. The cranial musculature blood flow was 2.4-fold the control value at 1 month and 1.4-fold the control value at 2 and 3 months. Skin blood flow was significantly elevated at 1 month after surgery (p less than 0.0277), but by 2 and 3 months, skin flow had decreased to 1.4-fold and 1.3-fold of control values (p = 0.22). Bone marrow and cortical blood flows were still significantly elevated at 3 months after surgery. Muscle blood flow remains markedly elevated 3 months after surgery. This study demonstrates the importance of soft-tissue blood flow to the process of revascularization, remodeling, and incorporation of avascular cortical bone. PMID- 1872555 TI - The Krukenberg procedure in the bilateral amputee after electrical burn. AB - Nine Krukenberg procedures were performed in 5 bilateral amputee patients suffering severe electrical injuries of both hands and wrists. The surgical procedure yielded functioning pincers in 7 of 9 operations. The patients could perform their daily activities very well and showed pronounced improvement in their self-confidence, self-reliance, and quality of life. The postoperative rehabilitation of these patients was not difficult. The Krukenberg procedure should be considered a substitute for prosthesis, especially in developing countries. PMID- 1872556 TI - Salvage of successful mandibular advancement for obstructive sleep apnea using a bipedicle osteocutaneous scapular free flap. AB - An interesting case is presented of a woman with obstructive sleep apnea due to mandibular hypoplasia who was successfully treated with mandibular advancement. After a postoperative complication, the correction was salvaged by using a previously undescribed bipedicled osteocutaneous scapular free flap. PMID- 1872557 TI - Sequential multiple free flap transfers for reconstruction of devastating hand injuries. AB - Restoring function to a severely damaged hand can require complex reconstructions using multiple tissue transfers to replace skeletal, soft tissue, and nerve components. We present 2 patients with severe hand trauma treated with serial multiple flap transfers, an operative sequence not previously reported in detail. One patient underwent five flap transfers in three operations, whereas the second patient underwent four flap transfers in two operations. All the flaps survived. Total anesthesia time for these patients was 43.5 and 34.5 hours, respectively. Both patients obtained measurable functional restoration, and suffered no significant perioperative morbidity. These patients illustrate the clinical feasibility of serial multiple microvascular transplantations for complicated reconstructions. PMID- 1872558 TI - Atypical mycobacterium soft-tissue infection of the dorsal radial wrist: a possible complication of steroid injection for de Quervain's disease. AB - Corticosteroid injection into the first dorsal compartment for acute de Quervain's tenosynovitis is an accepted form of therapy. Potential side effects include soft-tissue atrophy, tendon attrition, postinjection neuritis of the superficial radial nerve, systemic reactions, and infection. We present a patient with a Mycobacterium chelonei infection localized to the soft tissue overlying the first dorsal compartment, occurring 3 years after a triamcinolone injection into this area. Histological examination with the polarizing microscope revealed persistent steroid granules in the involved tissue. Successful treatment consisted of complete excision of the involved skin and subcutaneous tissue followed by delayed closure. Systemic antibiotics were not used. PMID- 1872559 TI - Survival of an upper lip aesthetic complex using arterial reanastomosis only. AB - Venous congestion after microvascular replantation remains a formidable problem even under ideal circumstances. The patient reported is a young woman with a traumatically avulsed upper lip aesthetic complex. Blood flow was reestablished using microanastomosis of the labial artery, however, no veins of adequate size could be recovered. With systemic administration of heparin, allowing the flap to bleed freely in addition to the use of medicinal leeches, we were able to salvage an avulsed upper lip aesthetic complex with the use of a single arterial microanastomosis. This patient report exemplifies alternative methods used in dealing with venous inadequacy in a composite replant. PMID- 1872560 TI - Restoration of facial contour with deepithelized pectoralis major musculocutaneous flap. PMID- 1872561 TI - Functioning free latissimus dorsi muscle transplantation: anterogradely positioned usage in reconstruction of extensive forearm defect. AB - We present a patient with successful functional recovery of a severely injured upper extremity after a microneurovascular free latissimus dorsi muscle and combined composite skin were transplanted with an anterograde position. In our patient, the anterogradely positioned usage of the lastissimus muscle offered two major advantages; one advantage was the direct anastomosis of a more proximal healthy uninjured recipient nerve without interpositional nerve graft, and the other, one-stage coverage including the elbow wound with combined scapular skin flap. From our result, we deduce that a neurovascular free latissimus dorsi muscle transplantation with an anterograde position is selectively indicated in functional recovery of an extensively injured forearm. PMID- 1872562 TI - Transaxillary subpectoral placement of textured breast prostheses. AB - Textured breast implants are difficult to introduce through a small incision. We have developed two new retractors and a new positioning regimen that enables us to use the transaxillary subglandular or subpectoral approach for breast augmentation. These retractors enable us to bluntly dissect the plane beneath the gland or the pectoralis muscle and then adduct the arm so that the relaxed pectoralis or subglandular space can be retracted to allow atmospheric pressure, gravity, and the surgeon's finger to work in unison. PMID- 1872563 TI - The importance of imprecision. PMID- 1872564 TI - Alcohol and the laboratory in the United Kingdom. AB - Reliable and rapid assays for the measurement of ethanol in breath and body fluids are now widely available. In view of the importance of alcohol abuse as a cause of a wide variety of both acute and chronic clinical conditions, hospital laboratories should be prepared to perform these assays for clinical purposes, although many will choose not to become involved in the assay of medico-legal samples. PMID- 1872565 TI - Primary hyperaldosteronism in England and Wales: a review of the use of a Supraregional Assay Service laboratory for the measurement of aldosterone and plasma renin activity. AB - To ascertain the use being made of a Supraregional Assay Service laboratory in the diagnosis of primary hyperaldosteronism, follow-up data were obtained on 60 patients in whom the diagnosis was suggested by the biochemical results. In 36 patients an adrenal adenoma had been removed; 14 patients had evidence of an adenoma on CT scan; 10 patients were presumed to have bilateral adrenal hyperplasia. The data used to make the diagnosis of primary hyperaldosteronism and to assess the likelihood of the presence of an adenoma indicate that patients studied at 40 centres in the UK show results very similar to those of North American series where large numbers of patients have been described but all have been studied in the same centre. The majority of patients in our series were treated at the hospital at which the diagnosis was made, thus avoiding referral to a centre distant from the patient's home and indicating that the service was being used as originally intended when the Supraregional Assay Service was set up. PMID- 1872566 TI - Pseudohyperphosphataemia in multiple myeloma. AB - Two cases of spurious hyperphosphataemia in patients with multiple myeloma are presented. An unreduced phosphomolybdate method without dialysis was used and the falsely raised values are shown to be due to the formation of a proteinaceous suspension in the reaction mixture. Such interference may be more prevalent than is generally recognized, and care should be taken to identify the problem in patients with myeloma. PMID- 1872567 TI - Hypercalcaemia due to calcium binding by a polymeric IgA kappa-paraprotein. AB - Total serum calcium concentration was raised in a 63-year-old lady with multiple myeloma and markedly elevated serum IgA kappa-paraprotein concentration. Symptoms of hypercalcaemia were absent, and serum ionized calcium was normal, suggesting calcium binding by the abnormal protein. This was demonstrated directly after isolation of the paraprotein and characterization of the calcium/protein interaction. After reduction of the paraprotein with mercaptoethanol, sodium dodecyl sulphate polyacrylamide gradient gel electrophoresis revealed two bands corresponding to light and heavy chains, but under non-reducing conditions the isolated paraprotein migrated in a series of bands, possibly representing polymeric forms of the basic immunoglobulin moiety. PMID- 1872568 TI - Effects of ionic strength on ionized calcium measured using reference electrode liquid junctions of varying design and composition. AB - Five commercial analysers were used to measure ionized calcium in aqueous and protein solutions which contained the same amount of calcium but had sodium chloride concentrations ranging from 100 to 150 mmol/L. In aqueous solutions measured activity fell significantly with increasing ionic strength while in protein solutions it increased. When isotonic sodium chloride was substituted for the hypertonic potassium chloride reference electrode liquid junction of an analyser with an open junction, there was a marked positive change in the effect of ionic strength in both aqueous and protein solutions. In contrast, when either isotonic sodium chloride or potassium chloride was substituted for the hypertonic potassium chloride of an instrument with a membrane-restricted junction, there was no effect on the change of measured values with ionic strength. Increasing the protein concentration by ultrafiltration did not change ionized calcium values when isotonic reference solutions were used with either open or membrane restricted junctions. Because membrane-restricted isotonic junctions respond like hypertonic junctions to changes in sample ionic strength but do not exhibit protein interference, they may prove to have advantages over both open isotonic junctions and all configurations of hypertonic junction for measurements in patients. PMID- 1872569 TI - In vitro evaluation of a heparinized blood sampler for ionized calcium measurement. AB - When ionized calcium measurements are needed urgently blood has to be sampled with an anticoagulant to allow rapid specimen processing. Heparinate salts cause a decrease in ionized calcium by binding which is clinically significant when the concentration exceeds 15 IU/mL of whole blood. The use of an anticoagulant in an aqueous state induces 'solution-dilution' errors. To avoid these two types of error the use of calcium-titrated sodium heparinate in a dry state has been proposed. However, in this situation the actual calcium concentration could be modified if its value were different from the titration level. This possibility has been studied using a commercially available sampler (Radiometer B-129). When the sampler was used as recommended, errors were non-significant around 1.25 mmol/L. There was a +3% increase for low (0.75 mmol/L) values and a -2% decrease for high (2.50 mmol/L) values. Incomplete syringe filling increased these errors. PMID- 1872570 TI - Different effects on oestrogen binding sites and anti-oestrogenic action of danazol and progesterone. AB - Rabbit uterus contains type I and II oestrogen binding sites in the cytosol, and nuclear fractions. Oestrogen-stimulated increase in uterine weight was inhibited by concurrent treatment with progesterone or danazol. Oestrogen-induced type I binding sites were decreased by progesterone and to a lesser extent by danazol, while oestrogen-induced type II sites were decreased almost equally in the two groups. Neither progesterone nor danazol alone caused any detectable changes in uterine weight. These findings may suggest that the anti-oestrogenic effect on uterine weight is more correlated with the change in type II binding sites of oestrogen than that in type I sites. Thus, danazol may exert anti-oestrogenic actions through a pathway independent from that of progesterone. PMID- 1872571 TI - Overestimation of monoclonal immunoglobulin by immunochemical methods. AB - A comparison of paraprotein estimation by scanning densitometry with corresponding immunoglobulin concentration measured by rate immunonephelometry, fixed-time immunonephelometry and kinetic immunoturbidimetry using a large number of sera has indicated overestimation of the immunoglobulin by liquid phase immunoassays in the presence of a monoclonal component. The effect was seen with all three major immunoglobulin isotypes but was most marked with IgM paraproteins when measured by kinetic nephelometry. The overestimations could not be explained by presence of rheumatoid factors or immune complexes in the serum samples, or by non-parallelism, over a range of dilutions, of the reaction of sample and calibrant with the antiserum. The source and species of antiserum used was a major contributory factor. PMID- 1872572 TI - Nasal secretions from patients with polyps and healthy individuals, collected with a new aspiration system: evaluation of total protein and immunoglobulin concentrations. AB - This study was designed, first, to test a new system for aspiration of human nasal secretions and, secondly, to evaluate protein and immunoglobulin concentrations in these secretions at different levels of secretory activity. The direct aspiration system combines the advantages of minimal irritation of the nasal mucosa with the facility to determine concentrations per gram of secretion. The total protein and immunoglobulin concentrations were inversely related to the amount of secretion obtained. Variations in fluid secretion throughout the day may be responsible for this relationship. The inverse relationship was much more significant in patients with nasal polyps, in which much higher concentrations were found, than in healthy subjects. Ratios of immunoglobulin to total protein were independent of the amount of secretion obtained. Compared to the controls, the ratios of IgM and IgG to protein in the secretions of the patients were significantly increased. The secretory immunoglobulin A to total protein ratios were only slightly higher in the patients' secretions. PMID- 1872573 TI - Immunoreactive endothelin in human kidney. AB - Using a sensitive and specific radioimmunoassay for endothelin, we examined immunoreactive endothelin in human kidney tissue obtained from three necropsy and three nephrectomy cases. Immunoreactive endothelin was present in high concentrations in human kidney inner medulla (necropsy cases: 1.08 +/- 0.47 pg/mg wet weight:mean +/- SE)(nephrectomy cases: 2.77 +/- 0.46). Characterization by reverse phase high performance liquid chromatography indicated that the only immunoreactive endothelin in human kidney inner medulla is endothelin-1, although immunoreactive endothelin in rat and pig kidney inner medulla comprises both isopeptides endothelin-1 and -3, suggesting that the genetic expression of endothelin differs according to species. PMID- 1872574 TI - A comparison of analytical goals for haemoglobin A1c assays derived using different strategies. AB - Analytical goals for the performance characteristics of assays of haemoglobin A1c (HbA1c) have been investigated using different assumptions for generation of estimates, these being based on strategies using data on biological variation and on the clinical use of results. The derived goals are highly dependent on the assumptions made. In general, in monitoring of patients (using results from the same laboratory), the analytical imprecision is the most demanding, whereas bias (inaccuracy) is the most important characteristic when strategies for several centres (laboratories) to achieve similar results are invoked. Goals for analytical quality should be given in a form in which both analytical imprecision and bias (or systematic error) are specified. When several goals are to be considered (for different relevant assumptions), the most demanding should be used. PMID- 1872575 TI - Fructosamine in diabetes screening of the elderly. AB - The use of serum fructosamine in diabetes detection was investigated during a diabetes survey performed with a modified oral glucose tolerance test (MOGTT) on 742 residents of the Melton Mowbray area aged between 65 and 85 years. Subjects were tested in the morning and remained at rest. MOGTT results were classified by WHO criteria. The fructosamine concentration was measured in a random sub-group of 264 normal subjects and had a Gaussian distribution (mean = 1.67 mmol/L, SD = 0.126 mmol/L). In the survey as a whole 25 new diabetics were found of which 23 had fructosamine measured; 17 had values above the 95th percentile and four more had values above the 90th percentile. We have found fructosamine concentration to be a useful screen for diabetes but this may be dependent upon the standardized sampling procedure used, and the population studied. PMID- 1872576 TI - A sandwich enzyme-linked immunosorbent assay for beta 2-glycoprotein I. AB - A solid-phase sandwich enzyme-linked immunosorbent assay for determining beta 2 glycoprotein I in urine has been developed. It has a working concentration range of 5-40 micrograms/L and a detection limit of approximately 1.4 micrograms/L. The within-plate coefficient of variation (CV) falls between 1.4% and 2.1%, and the between-batch CV ranges from 5.2 to 6.0%. Recovery of beta 2-glycoprotein I added to urine varies between 96 and 110%. The assay can also be used for determining beta 2-glycoprotein I in serum. PMID- 1872577 TI - Enzymatic determination of bilirubin in serum of newborns--any advantage over previous methods? AB - Using a Hitachi 705 Selective Analyzer at 25 degrees C, precision and accuracy of the enzymatic determination of total bilirubin (DRI-STAT) in serum of newborns was studied. Imprecision (day-to-day) was unacceptably high using daily calibration, but could be reduced by using a fixed factor. Accuracy was checked by analysis of 70 newborn sera with the 'Candidate Reference Method' and DRI STAT. It could be improved using calibrators with reference method values. Haemoglobin interference was studied by addition of different derivatives of fetal haemoglobin (oxihaemoglobin, desoxihaemoglobin, haemiglobin) to pools of newborn sera and control samples. DRI-STAT is more susceptible to interference by oxihaemoglobin than other routine methods. No difference was found in the influence of oxhihaemoglobin and desoxihaemoglobin; haemiglobin interferes significantly less. PMID- 1872578 TI - Reference ranges for free catecholamine/creatinine ratios in random urines from normal children aged 5 to 16 years. PMID- 1872579 TI - False positive reactions in total IgE analysis of amniotic and cerebrospinal fluids. PMID- 1872580 TI - Monitoring of renal transplant graft function by regular postal capillary blood sampling. PMID- 1872581 TI - Observed changes in serum potassium concentration following repeat centrifugation of Sarstedt Serum Gel Safety Monovettes after storage. PMID- 1872582 TI - Interference of fluorescein with creatinine assays. PMID- 1872583 TI - Fluorescein interference in digoxin assay: an isolated case? PMID- 1872584 TI - The relationship between serum cholesterol and serum thyrotropin in women with peripheral arterial disease. PMID- 1872585 TI - The evolving demographics of graduate dental education. AB - A review is provided of the changing gender, racial and ethic distribution of enrollees in advanced dental education programs. PMID- 1872586 TI - Retromolar foramen: a mandibular variant important to dentistry. AB - The retromolar foramen (RMF) was found to occur in eighteen of 234 adult human mandibles studied (7.7%). No statistically significant difference was found between left and right sides or between sexes. A statistical correlation was made between the occurrence of the RMF and accessory mandibular foramina, accessory mental foramina, mandibular third molars, and three-rooted mandibular first molars. Only the accessory mandibular foramen showed a significant positive correlation with RMF regarding same-side occurrence. Three-rooted first molars were not found in any of the mandibles studied. Due to the relatively frequent occurrence of RMF, it is important for the dental practitioner to be aware of this variant and the possible complications which may occur during the administration of anesthesia and surgical procedures in the region. PMID- 1872587 TI - An uncommon case of parotid sialolithiasis. AB - A vivid example of parotid sialolithiasis diagnosed with an anterior-posterior radiograph and subsequently followed with a superficial parotidectomy is presented. The case presentation is preceded and followed by a discussion of the pathogenesis and treatment of such an abnormality. PMID- 1872588 TI - Amniotic band syndrome (ABS): report of a case. AB - Amniotic band syndrome (ABS) is a rare collection of malformations associated with thread-like strands connecting the amnion and any part of the fetus. A case is reported where the constriction rings and amputation of fingers and the cleft lip/cleft palate constituted the main features of this syndrome. PMID- 1872589 TI - True malignant mixed tumor (carcinosarcoma) of palatal minor salivary gland origin. AB - True malignant mixed tumor (carcinosarcoma) of salivary gland origin is exceedingly rare and is distinguishable from the more frequently occurring carcinoma ex pleomorphic adenoma. This paper reports a case of true malignant mixed tumor originating from a palatal minor salivary gland of a 55-year-old male. Histologically, nests of poorly differentiated adenocarcinoma were scattered in a sarcomatous background which partially showed an unequivocal chondrosarcoma. Clinical course of the present patient suggested that a pre existing benign minor salivary gland lesion developed to a carcinosarcoma. PMID- 1872590 TI - The relationship between mercury from dental amalgam and oral cavity health. PMID- 1872591 TI - The New York Academy of Dentistry Merit Award in the Humanities. PMID- 1872592 TI - Failures of endocarditis prophylaxis: selective review of the literature and a case report. AB - Patients at risk for developing infective endocarditis require antibiotic prophylaxis before bloody dental procedures. However, despite prophylactic measures, some patients still develop the infection. A selective review of the literature is given and a case report of prophylactic failure in a high risk patient is presented. PMID- 1872593 TI - Therapeutic value of barley in the management of diabetes. AB - The alleged beneficial properties of barley in the treatment of diabetes were investigated. Rates of growth, water and food (digestible energy) intakes, and blood glucose concentrations were measured before and after the induction of diabetes in rats fed diets containing either barley or wheat. No differences were found in healthy animals, but in the diabetic state the blood glucose concentration, water consumption and weight loss was significantly lower in the rats fed barley. It is suggested that a factor other than the fibre content of the cereals may be responsible for the difference in response. PMID- 1872594 TI - Role of chromium in barley in modulating the symptoms of diabetes. AB - In adult diabetic rats, a diet containing barley had a modulating effect on the symptoms of diabetes (blood glucose concentration and water consumption) when compared with a starch or sucrose-based diet. It was postulated that the beneficial effect of barley might be explained by its very high content of chromium (5.69 micrograms/g). Supplementation of the sucrose-based diet with an amount of trivalent inorganic chromium calculated to be equivalent to the available chromium in the barley-based diet abolished the differences in response to the diabetic state. PMID- 1872595 TI - Effectiveness of education-screening on cholesterol levels of students. AB - Increases of cholesterol levels from the age of 16 years have been demonstrated in community-based studies. Cholesterol education to students aged 15-17 years in 5 high schools was presented prior to cholesterol screening with the Reflotron. First screening took place in March 1987. An identical program was repeated 11 months later, again followed by screening in March 1988. Of the 5 schools, 2 were assigned to involve teachers. There was a significant cholesterol reduction in these 2 schools, i.e., -17 and -19 mg/dl (p less than 0.05). The effectiveness of the physicians' education and the compliance of the students with the teachers' recommendations certainly must have been enhanced by a different family environment with a higher socioeconomic stratum prevailing in these 2 high schools. However, these factors did not influence the baseline in all 5 schools. In the 3 remaining schools no increases in cholesterol levels expected for this age were observed. PMID- 1872596 TI - Effect of supplementation with water-soluble vitamins on erythrocyte alanine aminotransferase activity of healthy adolescents. AB - The erythrocyte alanine aminotransferase (E-ALAT) activity with and without in vitro stimulation by pyridoxal phosphate of 60 healthy adolescents was measured before and after 6 weeks of supplementation with different water-soluble vitamins. The subjects who were divided into six groups received placebo (lactose tablets), pyridoxine, pyridoxine + ascorbic acid, pyridoxine + iron, pyridoxine + riboflavin and multivitamin supplements, respectively. Presupplementation E-ALAT activity increased significantly (p less than 0.05) for all supplemented subjects after 6 weeks. Deficient subjects (E-ALAT) index less than 1.16) however failed to respond to a combination of pyridoxine + ascorbic acid or multivitamins. It is suggested that pyridoxine in multivitamin preparations must exceed 1 mg to produce any useful improvement in vitamin B6 status of adolescents on suboptimal vitamin B6 intakes. PMID- 1872597 TI - Effect of protein malnutrition on glycoprotein, protein and lipid synthesis in the rat cerebellum during the period of brain growth spurt. AB - Female Wistar rats were fed a normal-protein diet (25% casein) or a low-protein diet (8% casein) during pregnancy and lactation. The two diets were isocaloric and contained appropriate amounts of mineral salts and vitamins. Pups from dams submitted to the low-protein diet had a lower body weight than normally fed controls as early as on the day of birth, but a difference in cerebellar weight between the two groups was observed only on the 15th postnatal day. Malnutrition had no effect on cerebellar protein concentration, which increased with age in both groups. The cerebellar DNA concentration was higher at 7 and 15 days of age in normally fed rats than in malnourished rats, whereas at 21 days of age it was higher in the malnourished animals. [U-14C]Leucine and [2-3H]mannose incorporation into proteins and lipid synthesis from acetyl coenzyme A (CoA) derived from [U-14C]leucine markedly decreased with age in the cerebellum of rats fed both diets. [2-3H]Mannose incorporation into cerebellar glycoproteins was greater in malnourished rats during the period of brain growth spurt than in normally fed rats at all ages studied. Prenatal and postnatal protein malnutrition had no effect on [U-14C]leucine incorporation into cerebellar proteins or on cerebellar lipid synthesis from acetyl-CoA derived from [U 14C]leucine during the period of brain growth spurt. PMID- 1872598 TI - Effect of changes of water and electrolytes on the validity of conventional methods of measuring fat-free mass. AB - Fat-free mass was measured by hydrodensitometry, electrical impedance and total body potassium before and after water and electrolyte loss induced by (a) the administration of the diuretic frusemide, and (b) sweat loss. All methods of measuring fat-free mass were shown by pilot experiments to have procedural reliability. The diuretic caused a reduction in apparent fat-free mass of 2.63 kg by the impedance method, of 2.33 kg by hydrodensitometry and of 1.8 kg by total body potassium. Water and electrolyte loss from sweating caused a fat-free loss of 2.3 kg, 2.7 kg and 1.3 kg by the same three procedures. Urinary potassium accounted for about one fifth of the observed 40K fat-free mass loss. Each method was thus clearly sensitive to the induced water loss. These data suggest that in evaluating the composition of weight loss, existing methods of measuring body composition do not distinguish between water and other more critical components of fat-free mass. It is thus essential that stable hydration levels are established for any longitudinal comparison of weight loss by these methods. PMID- 1872599 TI - Performance characterization of a model bioreactor for the biodegradation of trichloroethylene by Pseudomonas cepacia G4. AB - Pseudomonas cepacia G4 grown in chemostats with phenol demonstrated constant specific degradation rates for both phenol and trichloroethylene (TCE) over a range of dilution rates. Washout of cells from chemostats was evident at a dilution rate of 0.2 h-1 at 28 degrees C. Increased phenol concentrations in the nutrient feed led to increased biomass production with constant specific degradation rates for both phenol and TCE. The addition of lactate to the phenol feed led to increased biomass production but lowered specific phenol and TCE degradation rates. The maximum potential for TCE degradation was about 1.1 g per day per g of cell protein. Cell growth and degradation kinetic parameters were used in the design of a recirculating bioreactor for TCE degradation. In this reactor, the total amount of TCE degraded increased as either reaction time or biomass was increased. TCE degradation was observed up to 300 microM TCE with no significant decreases in rates. On the average, this reactor was able to degrade 0.7 g of TCE per day per g of cell protein. These results demonstrate the feasibility of TCE bioremediation through the use of bioreactors. PMID- 1872600 TI - Anaerobic biodegradation of cyanide under methanogenic conditions. AB - Upflow, anaerobic, fixed-bed, activated charcoal biotreatment columns capable of operating at free cyanide concentrations of greater than 100 mg liter-1 with a hydraulic retention time of less than 48 h were developed. Methanogenesis was maintained under a variety of feed medium conditions which included ethanol, phenol, or methanol as the primary reduced carbon source. Under optimal conditions, greater than 70% of the inflow free cyanide was removed in the first 30% of the column height. Strongly complexed cyanides were resistant to removal. Ammonia was the nitrogen end product of cyanide transformation. In cell material removed from the charcoal columns, [14C]bicarbonate was the major carbon end product of [14C]cyanide transformation. PMID- 1872601 TI - Role of sodium in the growth of a ruminal selenomonad. AB - The ruminal selenomonad strain H18 grew rapidly (mu = 0.50 h-1) in a defined medium containing glucose, ammonia, purified amino acids, and sodium (95 mM); little if any ammonia was utilized as a nitrogen source. When the sodium salts were replaced by potassium salts (0.13 mM sodium), there was a small reduction in growth rate (mu = 0.34 h-1), and under these conditions greater than 95% of the cell nitrogen was derived from ammonia. No growth was observed when the medium lacked sodium (less than 0.35 mM) and amino acids were the only nitrogen source. At least six amino acid transport systems (aspartate, glutamine, lysine, phenylalanine, serine, and valine) were sodium dependent, and these systems could be driven by an electrical potential (delta psi) or a chemical gradient of sodium. H18 utilized lactate as an energy source for growth, but only when sodium and aspartate were added to the medium. Malate or fumarate was able to replace aspartate, and when these acids were added, sodium was no longer required. Glucose-grown cells accumulated large amounts of polysaccharide (64% of dry weight), and when the exogenous glucose was depleted, this material was converted to acetate and propionate as long as sodium was present. When the cells were incubated in buffers lacking sodium, succinate accumulated and exogenous succinate could not be decarboxylated. Because sodium had little effect on the transmembrane pH gradient at pH 6.7 to 4.5, it did not appear that sodium was required for intracellular pH regulation. PMID- 1872602 TI - Anaerobic degradation of m-cresol in anoxic aquifer slurries: carboxylation reactions in a sulfate-reducing bacterial enrichment. AB - The anaerobic biodegradation of m-cresol was observed in anoxic aquifer slurries kept under both sulfate-reducing and nitrate-reducing but not methanogenic conditions. More than 85% of the parent substrate (300 microM) was consumed in less than 6 days in slurries kept under the former two conditions. No appreciable loss of the compound from the corresponding autoclaved controls was measurable. A bacterial consortium was enriched from the slurries for its ability to metabolize m-cresol under sulfate-reducing conditions. Metabolism in this enrichment culture was inhibited in the presence of oxygen or molybdate (500 microM) and in the absence of sulfate but was unaffected by bromoethanesulfonic acid. The consortium consumed 3.63 mol of sulfate per mol of m-cresol degraded. This stoichiometry is about 87% of that theoretically expected and suggests that m-cresol was largely mineralized. Resting-cell experiments demonstrated that the degradation of m cresol proceeded only in the presence of bicarbonate. 4-Hydroxy-2-methylbenzoic acid and acetate were detected as transient intermediates. Thus, the parent substrate was initially carboxylated as the primary degradative event. The sulfate-reducing consortium could also decarboxylate p- but not m-hydroxybenzoate to near stoichiometric amounts of phenol, but this reaction was not sulfate dependent. The presence of p-hydroxybenzoate in the medium temporarily inhibited m-cresol metabolism such that the former compound was metabolized prior to the latter and phenol was degraded in a sequential manner. These findings help clarify the fate of a common groundwater contaminant under sulfate-reducing conditions. PMID- 1872603 TI - In vivo metabolism of 2,2'-diaminopimelic acid from gram-positive and gram negative bacterial cells by ruminal microorganisms and ruminants and its use as a marker of bacterial biomass. AB - Cells of Bacillus megaterium GW1 and Escherichia coli W7-M5 were specifically radiolabeled with 2,2'-diamino[G-3H]pimelic acid ([3H]DAP) as models of gram positive and gram-negative bacteria, respectively. Two experiments were conducted to study the in vivo metabolism of 2,2'-diaminopimelic acid (DAP) in sheep. In experiment 1, cells of [3H]DAP-labeled B. megaterium GW1 were infused into the rumen of one sheep and the radiolabel was traced within microbial samples, digesta, and the whole animal. Bacterially bound [3H]DAP was extensively metabolized, primarily (up to 70% after 8 h) via decarboxylation to [3H]lysine by both ruminal protozoa and ruminal bacteria. Recovery of infused radiolabel in urine and feces was low (42% after 96 h) and perhaps indicative of further metabolism by the host animal. In experiment 2, [3H]DAP-labeled B. megaterium GW1 was infused into the rumens of three sheep and [3H]DAP-labeled E. coli W7-M5 was infused into the rumen of another sheep. The radioactivity contents of these mutant bacteria were insufficient to use as tracers, but the metabolism of DAP was monitored in the total, free, and peptidyl forms. Free DAP, as a proportion of total DAP in duodenal digesta, varied from 0 to 9.5%, whereas peptidyl DAP accounted for 8.3 to 99.2%. These data reflect the extensive metabolism of bacterially bound DAP within the gastrointestinal tracts of ruminant animals and serve as a serious caution to the uncritical use of DAP as a marker of bacterial biomass in the digesta of these animals. PMID- 1872604 TI - Methylated sulfur compounds in microbial mats: in situ concentrations and metabolism by a colorless sulfur bacterium. AB - The concentrations of the volatile organic sulfur compounds methanethiol, dimethyl disulfide, and dimethyl sulfide (DMS) and the viable population capable of DMS utilization in laminated microbial ecosystems were evaluated. Significant levels of DMS and dimethyl disulfide (maximum concentrations of 220 and 24 nmol cm3 of sediment-1, respectively) could be detected only at the top 20 mm of the microbial mat, whereas methanethiol was found only at depth horizons from 20 to 50 mm (maximum concentration of 42 nmol cm3 of sediment-1). DMS concentrations in the surface layer doubled after cold hydrolysis of its precursor, dimethylsulfoniopropionate. Most-probable-number counts revealed 2.2 x 10(5) cells cm3 of sediment-1, in the 0- to 5-mm depth horizon, capable of growth on DMS as the sole source of energy. An obligately chemolithoautotrophic bacillus designated strain T5 was isolated from the top layer of the marine sediment. Continuous culture studies in which DMS was the growth-limiting substrate revealed a maximum specific growth rate of 0.10 h-1 and a saturation constant of 90 mumol liter-1 for aerobic growth on this substrate. PMID- 1872605 TI - Effect of propionate toxicity on methanogen-enriched sludge, Methanobrevibacter smithii, and Methanospirillum hungatii at different pH values. AB - The effect of propionate toxicity at different pH values (6.5, 7.0, and 8.0) on methanogen-enriched sludge. Methanobrevibacter smithii, and Methanospirillum hungatii was studied. Organisms were grown in Balch medium 3 in Hungate tubes, and toxicity was characterized by a decrease in production of methane and in bacterial numbers. Propionate inhibited bacterial growth and cumulative methane production at concentrations as low as 20 mM. In the absence of propionate, the methanogen-enriched sludge and M. smithii showed better cumulative methane production at pH 6.5 and 7.0 than at pH 8.0. However, in the presence of propionate, these organisms showed better cumulative methane production at pH 8.0. M. hungatii differed in its behavior; the best values of cumulative methane production for this organism occurred at pH 7.0. Bacterial numbers reflected the microbial response to the presence of propionate. The highest counts of methanogenic bacteria were observed at pH 6.5 and 8.0. The numbers of methanogens were affected by the presence of propionate even at concentrations as low as 20 or 30 mM; at propionate concentrations above 80 mM, the methanogen count was affected by at least 2 orders of magnitude. Upon comparison of the responses of the pure cultures and the methanogen-enriched sludge to increasing propionate concentrations, it was found that the sensitivity of the pure cultures was similar to that of the methanogens in the sludge. PMID- 1872606 TI - Survival of Aeromonas salmonicida in lake water. AB - The survival of Aeromonas salmonicida subsp. salmonicida in lake water was investigated by using a variety of techniques. They included acridine orange epifluorescence, respiration, cell culture, cell revival, flow cytometry, plasmid maintenance, and membrane fatty acid analysis. During a 21-day study, A. salmonicida became nonculturable in sterile lake water samples. Flow cytometry and direct microscopy indicated that cells were present. Although the nonculturable cells could not be revived, the recovery method did indicate that the presence of low numbers of culturable cells within samples could produce misleading results. Plasmid DNA, genomic DNA, and RNA were maintained in the nonculturable cells; in addition, changes in the fatty acid profiles were also detected. Although viability could not be proven, it was shown that the morphological integrity of nonculturable cells was maintained. PMID- 1872607 TI - Novel cyanide-hydrolyzing enzyme from Alcaligenes xylosoxidans subsp. denitrificans. AB - A cyanide-metabolizing bacterium, strain DF3, isolated from soil was identified as Alcaligenes xylosoxidans subsp. denitrificans. Whole cells and cell extracts of strain DF3 catalyzed hydrolysis of cyanide to formate and ammonia (HCN + 2H2O- --HCOOH + NH3) without forming formamide as a free intermediate. The cyanide hydrolyzing activity was inducibly produced in cells during growth in cyanide containing media. Cyanate (OCN-) and a wide range of aliphatic and aromatic nitriles were not hydrolyzed by intact cells of A. xylosoxidans subsp. denitrificans DF3. Strain DF3 hydrolyzed cyanide with great efficacy. Thus, by using resting induced cells at a concentration of 11.3 mg (dry weight) per ml, the cyanide concentration could be reduced from 0.97 M (approximately 25,220 ppm) to less than 77 nM (approximately 0.002 ppm) in 55 h. Enzyme purification established that cyanide hydrolysis by A. xylosoxidans subsp. denitrificans DF3 was due to a single intracellular enzyme. The soluble enzyme was purified approximately 160-fold, and the first 25 NH2-terminal amino acids were determined by automated Edman degradation. The molecular mass of the active enzyme (purity, greater than 97% as determined by amino acid sequencing) was estimated to be greater than 300,000 Da. The cyanide-hydrolyzing enzyme of A. xylosoxidans subsp. denitrificans DF3 was tentatively named cyanidase to distinguish it from known nitrilases (EC 3.5.5.1) which act on organic nitriles. PMID- 1872608 TI - Assay for detection and enumeration of genetically engineered microorganisms which is based on the activity of a deregulated 2,4-dichlorophenoxyacetate monooxygenase. AB - An assay system was developed for the enumeration of genetically engineered microorganisms expressing a deregulated 2,4-dichlorophenoxyacetate (TFD) monooxygenase, which converts phenoxyacetate (PAA) to phenol. In PAA-amended cultures of Pseudomonas aeruginosa PAO1C(pRO103) and Pseudomonas putida PPO301(pRO103), strains which express a deregulated TFD monooxygenase, phenol production was proportional to cell number. Phenol was reacted, under specific conditions, with a 4-aminoantipyrine dye to form an intensely colored dye-phenol complex (AAPPC), which when measured spectrophotometrically could detect as few as 10(3) cells per ml. This assay was corroborated by monitoring the disappearance of PAA and the accumulation of phenol by high-performance liquid chromatography and gas chromatography. The AAPPC assay was modified for use with plate cultures and clearly distinguished colonies of PPO301(pRO103) and PAO1C(pRO103) from a strain expressing a regulated TFD monooxygenase. Colonies of P. putida PPO301(pRO101) remained cream colored, while colonies of PPO301(pRO103) and PAO1C(pRO103) turned a distinct red. PMID- 1872609 TI - Detection of enterotoxigenic Staphylococcus aureus in dried skimmed milk: use of the polymerase chain reaction for amplification and detection of staphylococcal enterotoxin genes entB and entC1 and the thermonuclease gene nuc. AB - The polymerase chain reaction was used to amplify the staphylococcal enterotoxin B and C genes (entB and entC1) and the staphylococcal nuclease gene (nuc). Two sets of primers ("nested primers") were found to be necessary for the detection of low copy numbers of purified DNA in diluent. These allowed detection of ca. 1 fg of purified target DNA, while 100 pg was required before detection of entB, entC1, and nuc with single primer pairs was possible. With nested primers, enterotoxigenic Staphylococcus aureus cells could be detected in artificially contaminated dried skimmed milk samples at levels of ca. 10(5) CFU ml-1 within 8 h. No cross-reaction was observed between the highly homologous entB and entC1 genes. The method showed total specificity for entC1 when tested against a wide variety of other bacteria. PMID- 1872610 TI - Effect of sublethal concentrations of four chemicals on susceptibility of juvenile rainbow trout (Oncorhynchus mykiss) to saprolegniosis. AB - The effects of sublethal concentrations of a variety of chemicals on the susceptibility of rainbow trout (Oncorhynchus mykiss) juveniles to Saprolegnia parasitica infection was examined. Sublethal concentrations of un-ionized ammonia (0.05 mg/liter) and nitrite (0.12 mg/liter) increased fish susceptibility after 10 days of exposure to the toxin, this increase being higher for ammonia (75% and 20% morbidity) than for nitrite (20% and 0% morbidity, respectively) with inoculum doses of 1.4 x 10(6) and 9.5 x 10(5) zoospores per liter, respectively. Sublethal concentrations of copper (0.05 mg/liter) or cyanide (0.05 mg/liter) did not show enhancement of infection by S. parasitica, even though the toxin exposure was for 21 days and the inoculum doses were higher than those for the experiments with the nitrogen compounds (4 x 10(6) and 3.2 x 10(6) zoospores per liter. However, infections began to appear in control animals. PMID- 1872611 TI - Purification and amino acid sequence of lactocin S, a bacteriocin produced by Lactobacillus sake L45. AB - Lactocin S, a bacteriocin produced by Lactobacillus sake L45, has been purified to homogeneity by ion exchange, hydrophobic interaction and reverse-phase chromatography, and gel filtration. The purification resulted in approximately a 40,000-fold increase in the specific activity of lactocin S and enabled the determination of a major part of the amino acid sequence. Judging from the amino acid composition, lactocin S contained approximately 33 amino acid residues, of which about 50% were the nonpolar amino acids alanine, valine, and leucine. Amino acids were not detected upon direct N-terminal sequencing, indicating that the N terminal amino acid was blocked. By cyanogen bromide cleavage at an internal methionine, the sequence of the 25 amino acids (including the methionine at the cleavage site) in the C-terminal part of the molecule was determined. The sequence was Met-Glu-Leu-Leu-Pro-Thr-Ala-Ala-Val-Leu-Tyr-Xaa-Asp-Val-Ala-Gly-Xaa Phe- Lys-Tyr-Xaa-Ala-Lys-His-His, where Xaa represents unidentified residues. It is likely that the unidentified residues are modified forms of cysteine or amino acids associated with cysteine, since two cysteic acids per lactocin S molecule were found upon performic acid oxidation of lactocin S. The sequence was unique when compared to the SWISS-PROT data bank. PMID- 1872612 TI - Dye to use with virus challenge for testing barrier materials. AB - Can FD&C Blue no. 1 dye photoinactivate bacteriophages phi X174, T7, PRD1, and phi 6 under laboratory lighting conditions? At high levels of light, the dye (500 microM) photoinactivated only phi 6. Thus, this dye can be used at concentrations up to 500 microM with bacteriophages phi X174, T7, and PRD1 to test barrier material integrity. PMID- 1872613 TI - Production of beta-carotene in Zymomonas mobilis and Agrobacterium tumefaciens by introduction of the biosynthesis genes from Erwinia uredovora. AB - The Erwinia uredovora crtB, crtE, crtI, and crtY genes required for beta-carotene biosynthesis were introduced by conjugal transfer into an ethanol-producing bacterium, Zymomonas mobilis, and a phytopathogenic bacterium, Agrobacterium tumefaciens, in which no carotenoid is synthesized. The transconjugants of Z. mobilis and A. tumefaciens carrying these genes appeared as yellow colonies and produced 220 and 350 micrograms of beta-carotene per g of dry weight, respectively, in the stationary phase in liquid culture. PMID- 1872614 TI - Establishment of Lactobacillus and Bifidobacterium species in germfree mice and their influence on some microflora-associated characteristics. AB - Germfree mice were inoculated with both Lactobacillus acidophilus A10 and Bifidobacterium bifidum B11. Both strains were established and present in more than 10(8) cells per g of cecum and colon contents. Furthermore, L. acidophilus A10 was established in high numbers in stomach and small intestine. Contents from different parts of the intestine were investigated with regard to the following microflora-associated characteristics: degradation of mucin, beta-aspartylglycine and tryptic activity, conversion of cholesterol to coprostanol and bilirubin to urobilinogen, deconjugation of bilirubin glucuronides, and reduction of the cecum size. In spite of being established, the microbes were not able to mediate any alterations of the parameters investigated. All animals retained values as found in their germfree counterparts. PMID- 1872615 TI - Involvement of a large plasmid in the degradation of 1,2-dichloroethane by Xanthobacter autotrophicus. AB - Xanthobacter autotrophicus GJ10 is a bacterium that can degrade short-chain halogenated aliphatic compounds such as 1,2-dichloroethane. A 200-kb plasmid, pXAU1, was isolated from this strain and shown to contain the dhlA gene, which codes for haloalkane dehalogenase, the first enzyme in the degradation pathway of 1,2-dichloroethane by GJ10. Loss of pXAU1 resulted in loss of haloalkane dehalogenase activity, significantly decreased chloroacetaldehyde dehydrogenase activity, and loss of resistance to mercuric chloride but did not affect the activity level of haloalkanoate dehalogenase, the second dehalogenase in the degradation of 1,2-dichloroethane. PMID- 1872616 TI - Low-molecular-weight xylanase from Trichoderma viride. AB - An endo-1,4-beta-xylanase (1,4-beta-D-xylan xylanohydrolase, EC 3.2.1.8) has been isolated from a commercial preparation of Trichoderma viride. The molecular weight was 22,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the pI value was 9.3. The xylanase was a true xylanase without cellulase activity. When the N-terminal amino acid sequence of the first 50 residues was compared with that of a xylanase from Schizophyllum commune, strong evidence for homology was found, with more than 50% amino acid identity. T. viride xylanase also possessed extensive identity with a proposed amino-terminal consensus sequence of xylanases from bacteria. PMID- 1872617 TI - Cloning of alginate lyase gene (alxM) and expression in Escherichia coli. AB - The alxM gene encoding a D-mannuronan-specific alginate lyase has been cloned from a marine bacterium isolated as an epiphyte on the brown alga, Sargassum fluitans. Expression of this gene in Escherichia coli provides a source of this enzyme for probing alginate structure and modifying the mannuronan-rich alginate polymers produced by bacterial pathogens. PMID- 1872618 TI - [Cancer therapy by using bispecific antibody]. AB - This paper reviewed recent researches and clinical trials using bispecific antibodies. Antibodies with two distinct binding specificities have great potential for a wide range of clinical applications as targeting agents for in vitro and in vivo immunotherapy. They have shown great promise for targeting cytotoxic effector cells, cytotoxic drugs, delivering radionuclides or toxins to tumor cells. We introduced potential applications of bispecific antibodies, and discussed the theoretical basis and problems associated with their production and purification, cell fusion and chemical conjugation techniques, and proposed a new manufacturing strategy by genetic engineering. This approach will enable the wide clinical application of bispecific antibodies for cancer immunotherapy. PMID- 1872619 TI - [Tissue levels of pirarubicin (THP) in dogs following intra-arterial infusion]. AB - The blood and tissue levels of pirarubicin (THP) were studied in dogs by HPLC analysis. The THP (1.5 mg/kg) was infused from the bifurcation of internal iliac artery. We measured the concentration of THP after 1 or 2 hours of intra-arterial infusion (IA) and compared with the concentration of THP administered intravenously (IV). The plasma levels of THP following IA rapidly disappeared the same as for IV. The blood cell level of THP following both IA and IV was significantly higher than the plasma level. The bladder mucosa and muscle levels of THP following IA were about 8 times as high as that of IV. The bladder muscle level of THP 2 hours after IA was about twice as high as after 1 hour and the same as the bladder mucosa level of THP after both 1 and 2 hours. It is considered that THP by the present method may have the transition from the mucosa to the muscle in the bladder. In the other intrapelvic tissues (perivesical adipose tissue, pelvic lymph node and prostate), IA also had higher concentrations compared with IV. However, the extrapelvic tissues (heart, liver and kidney) levels of THP following IA were the same as those for IV. It was concluded that THP was a reasonable agent for IA chemotherapy for bladder cancer. PMID- 1872620 TI - [Clinicopathological estimation of intra-arterial infusion chemotherapy of locally advanced breast cancer]. AB - The effect of intra-arterial infusion chemotherapy with adriamycin as a preoperating procedure was analyzed clinicopathologically in 30 cases with locally advanced breast cancer. A clinical response rate of 53.3% was obtained by the treatment and remarkable degenerative changes of tumor cells were noted histologically in the primary lesions. But there was no relationship between histological therapeutic effect and regression rate in tumors. A recurrence rate showed a higher correlation with histological therapeutic effect in comparison with clinical therapeutic effect. Especially, non-necrosis type that tumor cells were still alive mainly in the vessels showed significantly a higher recurrence rate in comparison with a central necrosis type or focal necrosis with fibrosis and hyalinization type. The local regional recurrence rate of patients receiving intra-arterial infusion chemotherapy was lower than that of patients, as the historical controls, receiving no therapy before operation. But prognostically, there was no significant difference in a survival rate between both groups. So, after operation, other alternative or multidisciplinary adjuvant chemo-endocrine therapy seems to be necessary for improving the survival rate. PMID- 1872621 TI - [Reservoir system implantation technique via the inferior epigastric artery]. AB - A reverse application technique of the radiofocus guidewire, as a guide for arterial cut down approach, was employed for the implantation of the reservoir system via inferior epigastric artery. Twenty five of the 26 patients succeeded in the implantation of reservoir system with this method, including two patients who were implanted two systems simultaneously. The advantages of this technique are as follows. Under the fluoroscopic examination, it is easy and safe to insert the catheter. There is no observation of the catheter dislocation, because the catheter does not get through the inguinal ligament. Two reservoir systems can be implanted simultaneously. This technique can be carried out immediately after the conventional angiography. With this technique, a high selective insertion rate (96%) of the catheter was achieved without no complication. This technique is feasible in implanting the reservoir system, but it is advisable for further studies to be made in order to clarify indications and further complications. PMID- 1872622 TI - [Hepatic arterial infusion of high dose 5-FU in weekly schedule for liver metastases from colorectal cancer employing a newly developed pump "Koken Infusor"]. AB - Seventeen patients with unresectable liver metastases from colorectal cancer were treated with 5 hour infusion of 1,000 mg/m2 of 5-FU in weekly schedule, employing a newly developed portable pump "Koken-Infusor". This pump is operated by batteries. It is small, light and easy to use. And five hundred cycles of treatments were performed, but the pump induced no major complications. The response evaluated by a CT-scan was 73% (11/15) without major toxicities. In conclusion "Koken-Infusor" is very useful for this treatment, especially for out patients. It appears that this therapy is one of the effective treatments for liver metastases from colorectal cancer. PMID- 1872623 TI - [Combination chemotherapy with orally administered UFT and leucovorin (LV)]. AB - We evaluated the efficacy of the combination therapy of UFT with Leucovorin (LV) against mouse colon adenocarcinomas and human colon adenocarcinoma. In vitro studies, it was shown that LV potentiated the cytotoxicity of FUra against 7 out of 9 cell lines used in this experiment. In vivo studies, the antitumor activity of UFT against mice bearing colon 38 adenocarcinoma was increased following administration of LV either before, after or at the time of treatment with UFT. Further studies were performed on the combination effect of UFT and LV against mouse colon 26 adenocarcinoma and human colon adenocarcinoma KM20C. Consequently, the combined treatment of UFT with LV was more effective than UFT alone against two cell lines. Our studies suggest that combination chemotherapy of UFT with LV is a promising approach for the treatment of a human colon cancer in clinical practice. PMID- 1872624 TI - [A late phase II study of CPT-11 on uterine cervical cancer and ovarian cancer. Research Groups of CPT-11 in Gynecologic Cancers]. AB - A late phase II study of CPT-11, a new derivative of camptothecin, in uterine cervical cancer and ovarian cancer was carried out by a cooperative study group at 26 institutions. Out of 144 patients enrolled, total cases were 110, involving 55 uterine cervical cancers and 55 ovarian cancers. In uterine cervical cancer, 5 cases of complete response (CR) and 8 cases of partial response (PR) were observed, with a response rate of 23.6% and a CR rate of 9.1%. In ovarian cancer, 13 cases of PR were observed, response rate was 23.6%. Both in uterine cervical cancer and ovarian cancer, the 95% confidence interval of response rate was 12.4 34.8%. In cases having undergone previous chemotherapy including platinum, derivatives, the response rate in ovarian cancer was 23.1% (12/52). In cases of uterine cervical cancer having previous radiotherapy, the response rate was 26.8% (11/41). In ovarian cancer of various histological types, a response was observed for not only serous cystadenocarcinoma but also mucinous cystadenocarcinoma, etc. A response was observed in distant metastatic lesions such as lung metastasis as well as primary lesion in uterine cervical cancer and ovarian cancer. Major adverse reactions were leukopenia, nausea and vomiting, diarrhea and anorexia, and these incidences (grade 2 or more) were 87.3, 60.3, 44.0 and 67.2%, respectively. Since some patients experienced severe adverse reactions, caution should be taken in treatment with CPT-11. Besides these reactions, alopecia was observed (33.1%), but severe adverse reactions such as nephropathy were not found. No significant difference in the efficacy and adverse reactions were observed between administration methods; A, 100 mg/m2 once weekly and B, 150 mg/m2 once every 2 weeks. Both were thought to be clinically useful. These results suggest that CPT-11 is clinically effective against uterine cervical cancer and ovarian cancer. PMID- 1872625 TI - [Experience of oral hormone-chemotherapy in prostatic cancer]. AB - Two oral anticancer agents, cyclophosphamide and UFT (mixture of futraful and uracil), were combined with hormone therapy for 42 patients with prostatic cancer. Although UFT could be taken for long periods, cyclophosphamide arose many problems such as the bone marrow suppression and gastrointestinal disturbances. The median length of the days they could take cyclophosphamide was sixty days. The survival rate of patients who were newly diagnosed and treated with this regimen was better than patients received hormone therapy only, and it suggests the possibility of the combined chemotherapy to inhibit the progression frequently observed after conventional hormone therapy. PMID- 1872626 TI - [A case of peritonitis carcinomatosa due to advanced gastric cancer effectively treated by intraperitoneal injection of carboplatin]. AB - The patient was a 72-year-old woman who had advanced carcinoma of the stomach. She presented massive ascites due to peritonitis carcinomatosa. The cytology of ascites was class V and the CEA level of ascites was elevated. Since renal function was low, we injected 300 mg of carboplatin intraperitoneally 2 times in 8 weeks. The amount of ascites was significantly diminished and the CEA level of ascites was decreased. The result suggested the effectiveness of intraperitoneal injection of carboplatin for the therapy of peritoneal metastasis of gastric cancer. PMID- 1872628 TI - [Complete response provided by new antitumor agent, MST-16 (sobuzoxane), in a breast cancer with multiple cutaneous metastases]. AB - A case of recurrent breast carcinoma was successfully treated with MST-16 in an early phase II study. A 60-year-old woman developed skin metastases on the forehead, neck, abdomen and back 8 months after receiving standard radical mastectomy for right breast carcinoma. MST-16 was given p.o. at the dose of 1,200 mg/body/day initially, and the dosage was modified thereafter depending on the grade of leukopenia. All metastatic lesions disappeared completely 38 weeks after the initiation of the treatment. The CR thus obtained has continued for 8 months up to the present. Although leukopenia was observed during the administration of MST-16, it could be well managed by dose modification. Further trials with this drug for breast carcinoma should be conducted, since complete responses are expected with few adverse effects as in the case under study. PMID- 1872627 TI - [Seven cases of eye involvement in adult with acute leukemia]. AB - Seven acute leukemia cases with oculomotor paralysis and/or optic nerve paralysis were reported. Five cases were lymphoblastic and two were myelogenous leukemia. The average age was 30.7 years old and male to female ratio was 5:2. The eye involvement developed during hematological complete remission stage in 4 cases, and during relapsing stage in 2 cases. For the remaining case, eye symptom was an initial symptom of the disease. The computed tomography of ocular region showed tumorous involvement in 3 cases and no abnormality in other 4 cases. The white blood cell count on admission was over 30,000/microliters and leukemic cells occupied over 59% of bone marrow nucleated cells in 5 cases. Intrathecal administration, a whole brain irradiation and intra-arterial injection of Nimustin as well as standard systemic chemotherapy were performed against oculomotor and optic nerve involvement. Leucoencephalopathy occurred in 2 of 7 cases after intrathecal administration and irradiation. Since 1980, continuous treatment for prophylaxis of central nervous system leukemia have been done and this protocol was effective for meningeal involvement but not for ocular involvement. PMID- 1872629 TI - [Activation of tegafur by cultured rat hepatocytes]. PMID- 1872631 TI - Nursing's agenda for health care reform. PMID- 1872630 TI - [Tumor markers--personal experience. A case report of primary lung cancer with interesting production of tumor markers]. AB - Three interesting cases of primary lung cancer from the standpoint of tumor marker production were reported. The first was a case of double cancers, one of which was sigmoid cancer without CEA production and the other a large cell lung cancer with CEA production. The evidence of elevated serum CEA level initially led to a wrong diagnosis as sigmoid cancer with lung metastasis. The second was a case which showed a relapse of monotonous cancer without CEA production after surgical removal of lung cancer tissue containing heterogeneous cancer cells. Elevated serum CEA levels were never observed after the operation, although the preoperative serum test was positive for CEA. The last was a case of squamous cell lung cancer which showed trophoblastic differentiation accompanied with massive hCG production. Very rapid tumor cell growth was seen after the early relapse following the operation. Positivity for hCG staining varied among primary and metastatic tumor tissues. PMID- 1872632 TI - ANNA's long-range strategic plan--year 2. PMID- 1872633 TI - Bridging the gap between competence and excellence. AB - As practicing nurses, as specialists, you find yourselves in two environments: (1) the inner world of your clinical practice and (2) the outer world of social, political, and economic influences. Your theme for this symposium has reminded you of the necessity of Bridging the Gap Between Competence and Excellence in Quest of Quality Care. To bridge that gap, you must operate effectively in both the inner and outer environment for caring. Through such means as I have mentioned, you can span the two worlds and emerge strong from the currents carrying us to the 21st century. You can stand upon the threshold of the future as a Renaissance nurse contributing to a reformed and revitalized profession. I salute you as you stand poised for action at the open door. PMID- 1872634 TI - The peritoneal equilibration test: a nursing discussion. AB - The peritoneal equilibration test is used to assess peritoneal membrane permeability. Results provide a reliable estimate of peritoneal clearances and ultrafiltration rates. This information can be used to make decisions about the preferred dialysis prescription. Repeat tests may be used to evaluate clinical changes. The first part of this two-article series will discuss the clinical interpretation of findings and three case studies. The second article will describe the procedure. PMID- 1872635 TI - How to do a peritoneal equilibration test. AB - This article, part 2 of a 2-part series, describes the process and procedures used to perform a peritoneal equilibration test. Data from the test may be used to assess the peritoneal membrane permeability. Knowledge of peritoneal membrane permeability may be useful in selecting a treatment regimen and in determining the appropriate dialysis prescription. PMID- 1872636 TI - Vascular access thrombosis in epoetin alfa therapy. AB - Correcting anemia in hemodialysis patients may cause an increased incidence of vascular access clotting. Therefore, the incidence of clotting in patients before and during therapy with epoetin alfa was investigated. The records of 45 hemodialysis patients were accessed by computer for data concerning thrombectomy procedures and administration of epoetin alfa during two 13-week periods. Before therapy, 2 out of 45 patients had clotted accesses for a rate of .18 thrombectomy procedures per patient year. During therapy, 7 out of 45 patients had 11 clotted accesses for a rate of 1 thrombectomy procedure per patient year. Clotting incidence was shown to be increased during the epoetin alfa therapy period. The consequences of delaying a dialysis treatment due to a clotted access may be significant and even life-threatening. Both physicians and nurses must have a good understanding of the possible role of epoetin alfa in access thrombosis for patient management. PMID- 1872637 TI - Functional capacity and activity level before and after renal transplantation. AB - Functional capacity and activity level were measured among 9 renal transplant recipients prior to transplantation (T1), 6 weeks (T2), and 16 weeks (T3) after transplantation. Functional capacity was measured by a symptom-limited treadmill test. The Human Activity Profile was used to obtain self-reported activity level. A 24% improvement in functional capacity was found from T1 to T2 with only a 5% improvement from T2 to T3 (p less than .001). In contrast, significant improvement in activity level was not present until after T2. Although activity level increased from T1 to T3 (p less than .01), it continued to be low in comparison with age/gender matched normative data. PMID- 1872638 TI - Reflections of a citizen soldier. AB - This article describes the author's experiences, impressions, and reflections on her 8 months of activation as an Army nurse in support of Operation Desert Shield and Operation Desert Storm. She was the chief nurse of the 3271st USAH based in Charleston that was sent to Winn Army Community Hospital in Fort Stewart, GA. This experience is contrasted with her previous experience as an active duty Navy nurse during the Vietnam era. PMID- 1872639 TI - ANNA Educational Resource List 1991. PMID- 1872640 TI - Teaching during dialysis. PMID- 1872641 TI - Case management of the anemic patient. Epoetin alfa: focus on self administration. AB - As of July 1, 1991, HCFA will reimburse for Epoetin alfa self-administered by home-based dialysis patients. Implications of this change, including the impact on patients and the changes that will be required to assure effective nursing assessment and optimal patient management, are reviewed. PMID- 1872642 TI - Contact between two compounds should be avoided. PMID- 1872643 TI - Practices of health care team towards blacks in organ donation must be targeted. PMID- 1872644 TI - Case study. ESRD after living-related donation. AB - The patient met three of the four expected outcomes. He has in the past and is currently making informed decisions. reguarding his health care. Momentarily, he is demonstrating effective, positive coping strategies and problem-solving techniques. However, the fourth, and probably most critical outcome, is not being met. A.J. has not remained free of complications secondary to his kidney donation. It is estimated that he is facing ESRD, and all related medical and nursing regimens in less than 1 year. Additionally related to his elective nephrectomy, he will experience the loss of his 12-year military career and associated benefits. Although the nursing interventions were instrumental in assisting A.J. and his wife to cope with his acute situation, they now face the fears and anxieties of lifetime chronic illness. Theoretically, this patient may have experienced chronic renal failure at some point in his life, but the nursing intervention could have been approached as a pre-ESRD patient, in lieu of his status as a postliving related donor patient. PMID- 1872645 TI - Back to the basics in iron management for the patient receiving epoetin therapy. PMID- 1872646 TI - alpha-Glucosidase, sperm ATP concentrations, and epididymal function. AB - It has been suggested that alpha-glucosidase may be a marker of epididymal patency and function. Spermatozoal ATP concentrations decrease during passage through the epididymis, indicating efficient maturation. We correlated sperm motility with seminal plasma alpha-glucosidase activity and spermatozoal ATP. The sperm motility correlation with alpha-glucosidase activity was significantly positive, and the sperm motility correlation with spermatozoal ATP was significantly negative. It appears that high-alpha-glucosidase activity and low spermatozoal ATP were present in semen with good sperm motility and could possibly indicate efficient epididymal function. PMID- 1872647 TI - Morphological and histochemical effects of 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) on marmoset (Callithrix jacchus) testes. AB - The testes of marmosets (Callithrix jacchus), which had been treated with a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.3 microgram to 10 micrograms/l kg body weight (BW)) were studied after 7 days using morphological and histochemical techniques. Light microscopic and electron microscopic examination revealed decreased intercellular contact in the germinal epithelium, as indicated first by enlarged intercellular spaces between the Sertoli's cells and between the Sertoli's cells and neighboring germ cells (i.e., spermatogonia and preleptotene spermatocytes), particularly in the basic compartment of the germinal epithelium. Second, decreased intercellular contact was indicated by the accumulation of premature spermatids and spermatocytes in the tubular lumen after TCDD treatment. The Sertoli's cells exhibited an increased amount of lipids, phagolysosomes, and vacuoles in their cytoplasm. Spermatids were frequently affected by TCDD, particularly during early spermiogenesis. These alterations included vacuolization of the cytoplasm and the development of additional germinal vesicles. This special effect on spermiogenesis became even more evident quantitatively by determination and counting of tubular stages in semithin sections. Tubular determination on the basis of the appearance of spermatids revealed that the ratio of tubular stages I to III became lower and that of stages V to VII became higher, dose dependently, indicating a maturation stop at the beginning of spermiogenesis caused by TCDD treatment. After TCDD treatment, Leydig's cells were morphologically unaffected, but histochemical investigations revealed decreased activity of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). The sensitivity of the applied methods was different in view of the level of unaffection. The effect of Leydig's cells, as indicated by the decreased activity of 3 beta-HSD, had already been found at a dose of 1 microgram/kg BW TCDD, whereas clear-cut morphological and morphometrical effects were seen at 3 micrograms/kg BW for the first time. Moreover, with the special effect on spermiogenesis in marmoset monkeys, the findings demonstrate that the toxicity of TCDD on testicular morphology is species specific. PMID- 1872648 TI - Influence of sperm processing on the fertilizing capacity and recovery of motile sperm from thawed human semen. AB - Artificial insemination programs now rely almost exclusively on frozen semen preparations as their source of sperm. Unfortunately, several reports indicate that conception rates using frozen-thawed semen are inferior to freshly ejaculated specimens. The present study was designed to investigate the fertilizing capacity of sperm and the recovery of motile sperm from thawed semen following different sperm processing methods. Washed resuspended pellets contained sperm with at least the same fertilizing potential as sperm from swim up techniques. However, the recovery of motile sperm from the pellets was more than 3 times greater than from the swim-up techniques. Percentage motility, progressive velocity, and amplitude of lateral head displacement were generally higher in the sperm from swim-up techniques than in the sperm from the pellets, despite equivalent fertilizing potentials. It can be argued from these results that washed resuspended sperm preparations provide a significantly greater number of motile sperm without a loss in fertility when compared to sperm from swim-up techniques. Accordingly, this study raises questions about the use of the sperm swim-up as a procedure for processing thawed semen for use in intrauterine insemination in which maximal numbers of motile sperm are required. It also demonstrates the need to identify new methods for processing frozen-thawed specimens for assisted reproductive procedures. PMID- 1872649 TI - Statistical analysis in andrology. AB - The authors began a statistical study on a file group of 9384 records of semen analyses and anamnestic data (P-1). From this file, they selected a group of 5191 patients having undergone analysis at least one time (P-2) and a file of 850 patients having undergone analysis at least three times (P-3). Finally a new group, derived from P-3, of 203 patients followed by their medical team was created (P-4). Two control groups-composed of 20 sperm-bank donors (DON) and 740 prevasectomy subjects (VAS)-were also created. Frequency distributions and cluster analyses were carried out. The multivariate statistical analysis allows a distinction to be made between fertile and infertile subjects regarding a patient's clinical condition. The most discriminating parameters appear to be sperm concentration and, above all, forward motility and sperm morphology. PMID- 1872650 TI - Semen parameters in men with and without proven chronic prostatitis. AB - In patients with complaints of chronic prostatitis, analysis of prostatic secretions for leukocytes and the use of the four-specimen technique allow a distinct classification of chronic bacterial (CBP), nonbacterial prostatitis (NBP), and prostatodynia (Pd). In this study, 32 men with CBP, 102 men with NBP, 142 men with Pd, and 42 volunteers, classified as mentioned above, underwent a two-fold ejaculate analysis using WHO criteria. Sperm count, progressive motility, range of abnormal spermatozoa, increased numbers of common bacteria, and peroxidase-positive leukocytes were analyzed. Additionally, antibody-coated bacteria (ACB), numbers of ureaplasmas in semen, and urethral colonization by chlamydia were investigated. Mean values of sperm density, motility, and morphology revealed no differences between the groups. Significant bacteriospermia (greater than or equal to 10(3) bacterial/ml) was evident in only 47% of the CBP group versus 6.8% (NBP), 16% (Pd), and 4.2% (controls). ACB was positive in 31 of 32 men with CBP versus 3 of 102 with NBP, 9 of 142 with Pd, and none of the controls. Increased numbers of leukocytes were evident in CBP and NBP patients compared to the controls (p less than or equal to 0.001) but were also present in patients of the NBP and Pd groups with chlamydial infections. PMID- 1872651 TI - Depressed semen quality in Swedish men from barren couples: a study over three decades. AB - The semen quality of men who participated in an infertility investigation in 1956 was compared with that from men from similar populations in the years 1966, 1976, and 1986. The sperm parameters studied included total sperm count and sperm morphology. A significant reduction over this 30-year period was observed for both parameters. The total sperm count decreased from 467 million in 1956 to 305 million in 1986 (mean, p less than 0.0001) and the percentage of sperm with normal morphology diminished from 53% to 37% (mean, p less than 0.0001) during the same period. This Swedish study, like studies in other industrialized countries, indicates a decline in semen quality over the past few decades. PMID- 1872652 TI - Hypo-osmotic sperm swelling test does not assess fertilizing capacity of human spermatozoa. AB - The hypo-osmotic sperm swelling (HOSS) test was performed on semen samples of five normospermic men from couples with prolonged infertility. Previously, the men had negative results of the zona-free hamster oocyte (ZFHO) test on two different ejaculates and the wives subsequently had become pregnant by donor insemination. A high swelling percentage (at least 60%) was found in all five men. It would appear that the HOSS test does not assess fertilizing capacity. PMID- 1872653 TI - Effects of varying the abstinence period in the same individuals on sperm quality. AB - Fourteen men each provided semen samples after 3, 6, and 10 days abstinence in a sequence decided by the individual and over a period of approximately 6 weeks. The proportion of sperm displaying progressive motility remained relatively constant up to 6 days but declined after a further 4 days of abstinence. This decrease was not associated with any major changes in sperm morphology or vitality. The total number of sperm with progressive movement in the ejaculate increased after 6 days and remained high after 10 days of abstinence. In subjects with asthenozoospermia, the greatest increase in the total number of sperm in the ejaculate occurred between 6 and 10 days. For men with reduced sperm quality participating in assisted fertilization programs, it may be advantageous to advise longer periods of abstinence, up to 10 days, prior to semen collection. PMID- 1872654 TI - New Mexicare. AB - An inexpensive plan is offered that provides access to basic, outpatient, primary, and preventive health care for all uninsured citizens of the State of New Mexico. New Mexicare rewards hospitals and hospital-affiliated specialists for inpatient care that is now unreimbursed. The establishment of a Health Care Trust Fund would create a mechanism that could influence the allocation of scarce and expensive resources to areas of need. New Mexicare would be set up within the State Medicaid Division and would be predicated on a mandate that all employers must provide health insurance with reasonable cost sharing by higher paid employees. It would not have great fiscal impact on small businesses, require complicated new tax rules, or impact current state revenues. New Mexicare solves the problem of the uninsured in incremental fashion and does not create an enormous administrative or budgetary burden to the state. It may be a suitable model for other states that share New Mexico's demography. New Mexicare could easily and rapidly be dissolved in the event that the federal government finally acts and provides universal access with some type of national plan. PMID- 1872655 TI - Pertussis in adults. What physicians need to know. AB - Although there is increased awareness among physicians regarding their role in protecting adults against vaccine-preventable diseases, many physicians are unaware that adults develop pertussis. Studies of adults with prolonged cough have found that 20% to 25% have serologic evidence of recent pertussis infection. Investigations of outbreaks have documented that adults develop infection with Bordetella pertussis and transmit the organism to susceptible children. Adults are the major reservoir of infection for children who may develop severe illness. Pediatric health care workers and patients infected with the human immunodeficiency virus might be at higher risk than the general population. Because most adults are susceptible to pertussis, physicians must consider pertussis in the differential diagnosis of patients with prolonged cough. Physicians who care for adults should be active in the diagnosis and treatment of pertussis, supportive of studies of the epidemiology of pertussis in adults, and interested in the development and testing of new diagnostic and preventive measures. PMID- 1872656 TI - Major infectious diseases causing excess morbidity in the Hispanic population. AB - Current data indicate that there are a number of infectious diseases, ie, acquired immunodeficiency syndrome/human immunodeficiency virus infections, cysticercosis, hepatitis A, syphilis, tuberculosis, and typhoid fever, among others that cause disproportionately increased morbidity in Hispanics. The greater rate of poverty with its associated socioenvironmental problems, increased barriers to health care, and importation of infectious diseases endemic in the mother country are some of the major reasons that probably account for this disparity in disease burden in Hispanics. This formidable health problem can be addressed by targeting efforts at improving health education of family units and communities, environmental improvements, elimination or reduction of barriers to health care management and disease prevention, and appropriate screening programs. A comprehensive and uniform assessment of the impact of infectious diseases on Hispanics (and other minorities) in this country remains elusive, but is of paramount importance in establishing priorities and effective/efficient strategies to address this issue. PMID- 1872657 TI - Quality of life before and after orthotopic hepatic transplantation. AB - Fifty-three nonalcoholic patients were evaluated prior to liver transplantation and again approximately 3 years after surgery using the Sickness Impact Profile and Social Behavior Adjustment Schedule. Test-retest scores reflected significant improvement across all health and psychosocial scales of the Sickness Impact Profile. On the Social Behavior Adjustment Schedule, significant improvement was observed on scales measuring disturbed behavior, social role performance, and burden. Comparisons between groups indicated that the liver transplant patients were still impaired on eight of the Sickness Impact Profile scales after transplant; however, the severity of disturbance was not considered to be clinically significant. No between-group differences were noted on the Social Behavior Adjustment Schedule. These results indicate that liver transplantation is associated with substantial improvement in life quality, although as a group, the patients undergoing this surgery do not recover to the level of functioning demonstrated by normal individuals. PMID- 1872658 TI - Changes in physician attitudes toward limiting care of critically ill patients. AB - To determine whether physician attitudes toward decision making in the care of critically ill patients have changed, a survey of physicians was conducted in 1981 and repeated in 1988. Physicians in 1988 were more comfortable discussing "do-not-resuscitate" options with patients and were more likely to allow a critically ill patient to die if the patient so requested. Most physicians in both surveys believe that treatment costs should not play a role in medical decisions. Trainees in 1988 were more aggressive in their management of case studies than were faculty in 1988 or trainees in 1981. While in both years the most important factors in the decision to treat aggressively were a patient's expressed desire to live or die and the amount of patient suffering, physicians in 1988 ranked malpractice concerns as a more important determinant in their decision process compared with physicians in 1981. Significant changes in physician attitudes toward the care of critically ill patients have occurred during this decade. PMID- 1872659 TI - Septic metastatic lesions of pyogenic liver abscess. Their association with Klebsiella pneumoniae bacteremia in diabetic patients. AB - Septic metastatic endophthalmitis from Klebsiella pneumoniae liver abscess, first reported in seven cases treated at the Veterans General Hospital, Taipei, Taiwan, between 1981 and 1985, was seen in six similar cases at the same hospital in the subsequent 2 years. We conducted a retrospective search for factors that might be associated with these complications of pyogenic liver abscess. A total of 23 cases with septic metastatic lesions from pyogenic liver abscess were found between 1981 and 1987, and 164 cases of pyogenic liver abscess without septic metastatic lesions were identified as a comparison group. Klebsiella pneumoniae liver abscess, bacteremia, and the underlying diabetes mellitus were significantly more common in the study group than in the comparison group. Of the 23 patients with septic metastatic lesions, there were 14 cases (60.8%) of endophthalmitis or uveitis, 10 cases (43.4%) of pulmonary abscess and/or emboli, six cases (26.0%) of brain abscess and/or purulent meningitis, five cases (21.7%) of bacteriuria and/or prostate abscess, two cases (8.6%) of osteomyelitis and/or pyogenic arthritis, and one case (4.3%) of psoas abscess. PMID- 1872660 TI - The adverse effects of hospitalization on drug regimens. AB - To determine the effect of hospitalization on errors in patients' drug regimens, 157 consecutive patients discharged on regimens of four or more drugs were identified, of whom 94 were eligible for study. Thirty-four (79%) of 43 local patients were interviewed within 1 month after discharge, and 28 (55%) of 51 patients who were mailed a questionnaire responded. Regimen errors were detected in 50% of both groups. Overall, 20 (32%) of 62 patients had incorrectly added or deleted a drug, and 11 (18%) were taking the correct drugs but had errors in dosing. Twelve potentially serious errors were detected. Patients with regimen errors had been discharged taking more drugs (6.1 vs 5.10) and tended to have more drug changes during hospitalization (2.7 vs 1.90). Particular attention should be paid to drug regimens during hospitalization and in subsequent follow up visits. PMID- 1872661 TI - Long-term treatment of 189 acromegalic patients with the somatostatin analog octreotide. Results of the International Multicenter Acromegaly Study Group. AB - BACKGROUND: We wanted to determine the clinical and biochemical effects of long term therapy with the somatostatin analog octreotide in 189 acromegalic patients. METHODS: Patients were treated at 23 medical centers for 6 days to 231 weeks (median, 24.2 weeks) with varying octreotide dosages (100 to 1500 micrograms/d; median, 300 micrograms/d). Serum growth hormone and insulin-like growth factor I (IGF-I) concentrations before and at the end of the study were compared, and correlations between the response to treatment with total daily dosage and duration of treatment were sought. RESULTS: The clinical response rate was 88%, irrespective of dosage or treatment duration. Serum growth hormone levels decreased in 172 (94%) of 182 patients and IGF-I levels decreased in 91 (92%) of 99. The mean pretreatment growth hormone level was 39.4 +/- 4.4 micrograms/L and decreased to 12.2 +/- 1.5 micrograms/L. Growth hormone levels decreased to less than 5 micrograms/L in 82 (45%) of 182 patients. The pretreatment IGF-I level was 5.62 +/- 0.41 U/mL and decreased to 2.64 +/- 0.19 U/mL; suppression to 2 U/mL or lower occurred in 46 (46%) of 99 patients. The degree of growth hormone suppression was associated with longer treatment duration but not with the total octreotide dosage per day. In 34 patients studied prospectively, pituitary tumor size decreased by greater than 20% in 15 (44%). Side effects occurred in 37% of patients and were most commonly transient loose alcoholic stools, pain at the injection site, and abdominal discomfort; severity was mild to moderate. Glucose tolerance was unchanged or improved in 52% and declined in 48% of 25 patients evaluated. CONCLUSIONS: Octreotide is an effective treatment for acromegaly that may be used as primary therapy or after surgery and/or pituitary irradiation. PMID- 1872662 TI - The value of roentgenographic and fiberbronchoscopic findings in predicting outcome of adults with lower lung field tuberculosis. AB - Proper antituberculosis chemotherapy may not prevent occurrence or progression of endobronchial involvement in patients with pulmonary tuberculosis. We previously reported a higher incidence of endobronchial involvement in adults with lower lung field tuberculosis (LLFTB). We evaluated the value of roentgenographic and fiberbronchoscopic findings in predicting the outcome of adults with LLFTB after 9 months of antituberculosis chemotherapy. The most common change on chest roentgenograms among 101 patients with LLFTB was consolidation, followed by cavitary lesion, lung collapse, and solitary mass. Intrathoracic lymphadenopathy (hilar and/or mediastinal lymphadenopathy) was found in 12 cases. Sputum smear for acid-fast bacilli was positive in 64 patients, and sputum culture for tuberculous bacilli was positive in 37 of 50 patients. Endobronchial involvement was found in 45 of 63 patients who underwent fiberbronchoscopic examination. Of these 45, 18 had ulcerative granuloma, 12 had fibrostenosis, eight had submucosal infiltration, and seven had mucosal redness and swelling. A higher incidence of endobronchial involvement was found in the patients with LLFTB when they presented with roentgenographic findings of pulmonary consolidation, lung collapse, or associated intrathoracic lymphadenopathy. The outcome seemed unfavorable in the patients with LLFTB who presented with roentgenographic findings of lung collapse or pulmonary consolidation, or in those who presented with fiberbronchoscopic findings of fibrostenosis or ulcerative granuloma. Our results show that roentgenographic and fiberbronchoscopic findings are of value in predicting outcome of patients with LLFTB. With proper antituberculosis chemotherapy and close follow-up, fiberbronchoscopy may be clinically indicated in patients with LLFTB to assess the presence and severity of endobronchial involvement. Early surgical intervention can be considered in those with severe endobronchial involvement before serious sequelae occur. PMID- 1872663 TI - Use of random urine samples to estimate total urinary calcium and phosphate excretion. AB - Calcium-to-creatinine and phosphate-to-creatinine ratios in random single-voided urine specimens were compared with 24-hour calcium and phosphate excretions, respectively, in 67 subjects who were selected prospectively to represent a wide range of renal and parathyroid function as well as urinary calcium and phosphate loss. Simple linear regression analysis revealed significant correlation between the spot urine calcium-to-creatinine ratio and 24-hour total calcium excretion and between the spot urine phosphate-to-creatinine ratio and 24-hour phosphate excretion. Calculating these simple ratios permits easy, rapid, correct, and inexpensive estimation of the daily urinary calcium and phosphate excretion. PMID- 1872665 TI - Hemochromatosis, iron and septicemia caused by Vibrio vulnificus. AB - Vibrio vulnificus is killed by normal human blood but grows rapidly in blood from patients with hemochromatosis. It also grows in normal blood if the saturation of the transferrin is increased or if hematin, which contains iron, is added. It is suggested that the increased availability of iron in the blood of patients with chronic iron overload is responsible for their enhanced susceptibility to infection with V vulnificus. PMID- 1872664 TI - Hypocholesterolemic effects of different bulk-forming hydrophilic fibers as adjuncts to dietary therapy in mild to moderate hypercholesterolemia. AB - Hypercholesterolemia is a significant risk factor for coronary heart disease, and the hypocholesterolemic effects of psyllium are well established. This placebo controlled, parallel study compared psyllium with methylcellulose, calcium polycarbophil, and placebo as dietary adjuncts in treating mild to moderate hypercholesterolemia. Of 163 men and women recruited with serum cholesterol levels above 5.17 mmol/L (200 mg/dL), 105 completed 8 weeks of an American Heart Association step I diet and then augmented the diet with one of the fiber supplements for 8 additional weeks. Incremental differences from placebo for low density lipoprotein cholesterol were -8.8% for psyllium, -3.2% for methylcellulose (not significant), and +8.7% for calcium polycarbophil; and for total cholesterol the differences were -4.3% for psyllium (not significant), 1.4% for methylcellulose (not significant), and +5.9% for calcium polycarbophil. Compliance was 94% to 96%, and only mild gastrointestinal side effects were observed. In managing mild to moderate hypercholesterolemia, methylcellulose and calcium polycarbophil provide little or no additional benefit, while psyllium significantly enhances the American Heart Association diet effects. PMID- 1872666 TI - Comparison of the lipid profiles of Cubans and other Hispanics with non Hispanics. AB - We compared the plasma lipid profiles of Cuban Americans and other Hispanic American subgroups with those of non-Hispanics. High-density lipoprotein cholesterol levels were lower and triglyceride levels were higher when Hispanic women were compared with non-Hispanic women, and this pattern was also apparent for men. The lower high-density lipoprotein cholesterol and higher triglyceride levels were consistent for both Cuban and non-Cuban Hispanics. There were higher waist-hip ratios and insulin levels in both Hispanic men and women. When allowances were made for these attributes in covariance analyses, the lipid differences were markedly diminished. These data suggest the lower high-density lipoprotein cholesterol and higher triglyceride levels are consistent across Hispanic subgroups and that this lipid pattern may be attributable at least in part to increased insulin resistance in Hispanics. PMID- 1872667 TI - Clinical significance of a dizziness history in medical patients with syncope. AB - To determine the implications of dizziness as a symptom in patients with syncope, we analyzed responses to a standardized battery of questions about dizziness in 121 consecutive patients referred for evaluation of syncope. Associations were sought between final diagnosis (dependent variable) and clinical predictor variables. Dizziness was found in 70% of the patients with syncope. Dizzy patients were younger (mean ages, 47 vs 56 years, respectively), more often female (75% vs 42%), and more likely to be assigned a psychiatric diagnosis. Multivariable logistic regression analysis identified young age and rotatory dizziness (vertigo) to be associated with a psychiatric diagnosis. Dizziness and syncope frequently coexist and in many cases may represent the same pathophysiologic process. A careful dizziness history may guide the initial evaluation of syncope patients in clinical practice. PMID- 1872668 TI - Use of centrally acting sympatholytic agents in the management of hypertension. AB - Considerable evidence suggests that hyperactivity of the sympathetic nervous system is implicated not only in the pathogenesis of essential hypertension but also in several blood pressure-independent complications of essential hypertension. Even with the advent of newer antihypertensive agents, including angiotensin-converting enzyme inhibitors and calcium antagonists, the centrally acting sympatholytics (alpha 2-adrenoceptor agonists) remain a valuable group of medications for the management of hypertension of all grades of severity. Their advantages include efficacy; rarity of contraindication; absence of most metabolic and serious side effects; favorable effects on systemic hemodynamics; lack of true tolerance and infrequency of volume expansion-related pseudotolerance; suitability in the elderly, in isolated systolic hypertension, and in patients with various concomitant conditions, such as diabetes mellitus; ability to reverse left ventricular hypertrophy; and relative low cost. The long duration of action of guanfacine hydrochloride, the most recently marketed agent, and of the transdermal formulation of clonidine is an especially commendable feature. The principal disadvantages of this class of medications are an overlap between the therapeutic dosage and that producing sedation and dry mouth and the potential to cause the discontinuation syndrome and sexual dysfunction. PMID- 1872669 TI - National adverse drug reaction reporting. 1984-1989. AB - Surveillance of adverse reactions due to pharmaceuticals is important because the drug approval process cannot totally assure safety and because new knowledge is bound to accrue after drugs enter usual medical practice. Reporting of reactions to the Food and Drug Administration increased markedly between 1985 and 1989 and totaled 261,515 reports for this period. A large part of this increase was due to new legal requirements, which ensure that manufacturers report reactions to the Food and Drug Administration. Most reaction reports originated with practicing physicians who contacted drug manufacturers. High proportions of the reports involved new drugs and serious reactions. Reaction surveillance leads to 50 to 100 important safety investigations annually and to numerous changes in product information. Health care providers must continue to report suspect adverse reactions to the Food and Drug Administration and manufacturers if pharmaceutical use and safety are to improve. PMID- 1872670 TI - Treatment of Wegener's granulomatosis with sulfamethoxazole-trimethoprim. AB - Sulfamethoxazole-trimethoprim may be an alternative or adjunctive treatment for Wegener's granulomatosis, as suggested by our experience with six patients. Two had limited Wegener's granulomatosis; one of these achieved remission with sulfamethoxazole-trimethoprim alone, and the second achieved remission with sulfamethoxazole-trimethoprim and prednisone. Four patients presented with sinus, pulmonary, and renal involvement. One patient initially treated with sulfamethoxazole-trimethoprim developed worsening renal function requiring cytotoxic therapy. Two patients initially treated with cytotoxic agents achieved remission coincident with the addition of sulfamethoxazole-trimethoprim for persistent sinus symptoms. One patient had relapse of pulmonary symptoms after achieving and maintaining a remission during treatment with sulfamethoxazole trimethoprim alone. This experience suggests that sulfamethoxazole-trimethoprim may be an effective treatment for some patients with Wegener's granulomatosis and may be the only agent required. Patients require careful follow-up and still may need cytotoxic therapy. PMID- 1872671 TI - Lung abscess with group A beta-hemolytic Streptococcus. Case report and review. AB - Invasive infections with group A beta-hemolytic streptococci became less common in the early 20th century prior to the widespread use of antibiotics. From the early 1960s until the mid-1980s, reports of invasive infections continued to decline. In the past 5 years, there has been a resurgence of invasive infections and, possibly, also of postinfectious sequelae from this organism. We describe a patient with lung abscess from group A beta-hemolytic Streptococcus. Lung abscess from hemolytic streptococci was not uncommon in Osler's day, but it was not reported in the English-language literature for 20 years until recently. Clinicians should be aware of the broad and growing spectrum of infections with this pathogen. PMID- 1872672 TI - Angle closure glaucoma precipitated by aerosolized atropine. AB - Angle closure glaucoma is an infrequent form of glaucoma occurring when the filtration mechanism for the aqueous humor is obstructed by apposition of the peripheral iris to the trabecular meshwork. Anatomic features associated with acute-angle closure include congenitally small anterior segments, increased lens thickness, and shallow anterior chamber depth. We present two patients who developed signs and symptoms of angle closure glaucoma after receiving aerosolized atropine for treatment of chronic obstructive pulmonary disease. We recommend that before instituting therapy with an inhaled anticholinergic agent, the patient should be questioned concerning prior history of angle closure glaucoma symptoms and signs and the anterior chamber depth should be examined using iris illumination. Patients having shallow anterior chambers, or possible prior angle closure glaucoma attacks, should be examined by an ophthalmologist before inhalant anticholinergic therapy. PMID- 1872673 TI - Can vitamin D deficiency produce an unusual pain syndrome? AB - An unusual pain occurred in five patients in the presence of compromised vitamin D status and resolved 5 to 7 days after supplementation with vitamin D in the form of ergocalciferol. The pain had a hyperesthetic quality and did not respond to the use of analgesics, including opiate derivatives. Treatment with therapeutic levels of a tricyclic antidepressant did not bring relief of symptoms. In one case, months after treatment and subsequent improvement of vitamin D status and pain, the vitamin D status again declined and the pain recurred. The pain again resolved with vitamin D replacement and improvement of levels. There may be a pain syndrome associated with vitamin D depletion that appears as hyperesthesia worsened by light, superficial pressure or even small increments of movement. This pain restricts mobility and function and may lead to further complications, such as pressure sores. PMID- 1872674 TI - Lovastatin-induced lupus erythematosus. AB - Two patients, a 64-year-old woman and a 40-year-old man, developed a lupuslike syndrome due to lovastatin therapy, confirmed by signs, symptoms, and positive fluorescent antinuclear antibodies are herein published. The lovastatin-induced lupus was completely reversible on withdrawal of the agent. PMID- 1872675 TI - Sleep and nasal disease. PMID- 1872676 TI - Angiotensin-converting enzyme inhibitors (ACE) in congestive heart failure. PMID- 1872677 TI - All ACE Inhibitors are not alike. PMID- 1872678 TI - Disseminated infection with Pneumocystis carinii related to administration of pentamidine aerosol. PMID- 1872679 TI - Helicobacter pylori in Seventh-Day Adventists? PMID- 1872680 TI - The experience of house officers. PMID- 1872681 TI - J-curve during hypertension control: rationale for not lowering the diastolic pressure below 85 mm Hg. PMID- 1872682 TI - Accuracy of cholesterol measurements. PMID- 1872683 TI - The interstitial nucleus of Cajal of the cat. I. Neurons activity related to vertical eye movements. AB - Interstitial nucleus of Cajal (INC) neurons activity was studied during vertical optokinetic nystagmus (OKN) and after-nystagmus (OKAN) in awake cats lying on their right side. The activity of one hundred neurons was recorded in the left INC and analysed in relation with the vertical component of OKN and OKAN. The activity of 27 neurons was correlated either to eye position or to both eye velocity and eye position; 18 of these neurons were recorded in their on direction and their off-direction. The analysis of the 18 neurons showed that the activity of 8 of them was correlated to eye position in the on-direction and in the off-direction and the correlation to eye position was higher than to eye velocity; these neurons are considered as position neurons. Seven other neurons had a higher correlation to eye position that to eye velocity in the on-direction and this relation reversed in the off-direction, these neurons are considered as position-velocity neurons. Thirty two burst-neurons were activated only during quick phases of OKN and OKAN and they were silent during slow phases and periods of fixation. Nine burst neurons had an upward on-direction and 23 neurons a downward on-direction. The eye velocity-average burst frequency (ABF) and quick phase duration-burst duration relationships had low correlations and suggested that INC burst neurons were excitatory premotor neurons. Statistical analysis showed that downward on-direction burst neurons had a higher ABF that upward on direction burst neurons. Moreover, during OKN and OKAN, the velocity sensitivity of INC burst neurons was the same. The activity of the remaining neurons (41 neurons) was not quantitatively correlated to vertical and horizontal eye movements; they were classified as irregular tonic neurons. This study shows that INC neurons carry an eye position signal which was never reported before. This supports the results of INC lesion studies which showed that INC is involved in the vertical velocity to position integration. Moreover, there is an up versus down asymmetry in the frequency of INC burst neurons. PMID- 1872684 TI - The interstitial nucleus of Cajal of the cat. II. Effects of kainic acid lesion on vertical optokinetic nystagmus and after-nystagmus. AB - The effects of bilateral lesions of the interstitial nucleus of Cajal (INC) by kainic acid on vertical optokinetic nystagmus (OKN) and after-nystagmus (OKAN) were studied in four cats: in three cats, in the acute stage from 1 to 60 days after the lesions; in the fourth cat, they were studied 3 years after the lesions were made. Histological control of lesions showed that the whole INC was bilaterally destroyed in two cats of the acute group and only the upper part of INC in the third cat. In the chronic cat, the density of cell bodies in both INC was lower than normal. In the acute group, the cats exhibited a spontaneous downward eye drift in light and in darkness. During an upward optokinetic stimulation, the effect of INC lesions was dramatic: upward slow phases and downward quick phases of OKN were abolished. Sixty days post lesions, small upward slow eye movements were again observed. During a downward optokinetic stimulation, the defect was much less; in particular, after a slight impairment of downward slow phases, during the first days post lesions, they recovered quickly. The secondary optokinetic after nystagmus (OKAN II) ensuing a downward OKN was cancelled and did not reappear 60 days post lesions. In the chronic stage, three years after the lesions, during an upward optokinetic stimulation, the cat showed upward slow phases with velocities close to normal. However, upward slow phases were curved: the velocity at the end of the slow phases was lower than at the beginning. After an upward OKN (the direction of slow phases gives the direction of the OKN and OKAN), the ensuing OKAN was present but abnormal. PMID- 1872685 TI - Instrumental conditioning of skin potential responses in curarized cats: non specific effects of a punishment procedure. AB - This study evaluates the effects of a punishment paradigm upon electrodermal activity (EDA) in curarized cats. In ten experimental subjects, any skin potential response (SPR) exceeding threshold value was punished by an electric shock. Ten control subjects received an electric shock or an electric stimulation of the mesencephalic reticular formation unrelated to the EDA. The results show that: a) No significant modifications of EDA occurred in subjects characterized by low initial activity; b) The frequency of SPR significantly decreased in high activity subjects used both for the experiments and the controls. Therefore, this diminution, in experimental subjects, cannot be due to a learning process. Neither can it be related to level of curarization or to rate of artificial ventilation. It is suggested that this effect results from a non-specific cortical inhibitory mechanism acting on the reticular activating system. The results obtained in three decorticated cats submitted to a punishment procedure are in accordance with such an hypothesis. Consequently the existence of operant autonomic learning remains unproven. PMID- 1872686 TI - Effects of Chinese herbal drug, dai-saiko-to on plasma lipids, lipoproteins and liver lipid contents in guinea pig. AB - Effects of Chinese herbal drug, Dai-saiko-to, on plasma lipids, lipoproteins and liver lipid contents were investigated in guinea pig with/without cholesterol feeding. Guinea pigs were divided into 4 groups (Group 1: normal chow (N) diet, Group 2: N + 1% Dai-saiko-to (D) diet, Group 3: 1% cholesterol (C) diet, Group 4: 1% C+ 1% D diet), and were treated for 5 weeks. Significant body weight reductions were observed in Groups 3 and 4 compared to Groups 1 and 2. Significant reductions of plasma triglyceride (TG) and very low and low density lipoproteins [(V) LDL]-TG were found in Group 3 compared to Groups 1, 2, and 4. (HDL)-TG significantly decreased in Groups 3 and 4 compared to Groups 1 and 2, but no significant difference was noted between Groups 1 and 2, and Groups 3 and 4. Liver lipid contents analysis showed no significant changes between Groups 1 and 2, and Groups 3 and 4, respectively, but the distribution of lipid droplets as pathologically determined using a computer program showed Group 4 had less lipid deposition compared to Group 3. These data suggest that Dai-saiko-to acts on triglyceride metabolism in hypercholesterolemic guinea pigs. PMID- 1872687 TI - [Morphometric characteristics of tissue basophils in cancerous and precancerous diseases of the skin]. AB - Skin of 60 patients with squamous cell non-keratinizing carcinoma, basaliomas, Bowen carcinoma, hyperkeratosis, papillomatosis and chronic inflammation was studied using routine histological and histochemical methods. The number of basophils was calculated; the index of their heparin saturation, degree of granulation was determined by division of a number of highly granulated labrocytes by a number of the least granulated labrocytes and multiplying the result by 100. The results may serve as a criterion in the evaluation of the degree of skin carcinoma cataplasia. PMID- 1872688 TI - [Morphometric features of breast cancer cells in the evaluation of the degree of tumor differentiation]. AB - Morphometric study of the cell and nucleus surface as well as nucleus cytoplasmatic ratio are performed in 80 patients with mammary carcinoma using a Soviet cytoanalyzer "Integral-2MT". Highly differentiated carcinomas are characterized by a domination (61.3%) of small nuclei (up to 120 microns 2). Moderately differentiated carcinomas are polymorphic by their composition: 43.3% nuclei up to 120 microns 2, 39.3% from 120 to 160 microns 2, remaining nuclei are of a large size. Poorly differentiated carcinomas are even more polymorphic due to high percentage of large nuclei--from 140 to 200 microns 2 and larger representing 46.5% cells. The analysis of nuclear size distribution allows estimation of the degree of cell differentiation in the tumour. PMID- 1872689 TI - [Alveolar macrophages in lung physiology and pathology]. AB - Alveolar macrophages (AM) represent a lung border system bringing about the protection of the organ from the environmental hazards, regulating cell and humoral response in the lungs, and eliminating endogenous toxic substances. However, in some situations AM are involved in the pathologic processes and even may serve as an initiating factor in the development of lung pathology. They realize their pathogenic effect in the bronchial asthma, acute respiratory distress-syndrome, pneumoconiosis releasing various biologically active compounds which take part in the formation of bronchial hyperreactivity, chemotaxis disturbances, haemostasis pathology. Particularly interesting is the possibility of lung tissue damage by AM when they interact with endotoxin-positive granulocytes. PMID- 1872690 TI - [Hyperplastic changes in the mucosa in colon cancer]. AB - 67 segments of rectum and sigmoid removed surgically because of carcinoma were examined: the surface of intestinal mucosa stained with methylene-blue was studied in order to determine the number and localization of focal changes in the macroscopically unchanged areas. Colon microscopy was performed clinically in 24 patients with carcinoma of the rectum and in 24 control individuals. 28 hyperplastic polyps and 1037 microscopic hyperplastic foci were found in operative material. An active metabolism is established by means of electron autoradiography in the cells of hyperplastic focus. Areas of dysplastic epithelium were rarely found in big hyperplastic polyps. Areas of diffuse hyperplasia (transitional mucosa) with crypt deepening and presence of a high number of goblet cells were found near tumour. A certain role of hyperplastic processes in carcinogenesis is forwarded. Numerous microscopic changes in the mucosa epithelium may testify against the carcinoma development de novo. PMID- 1872691 TI - [Ultrastructure of human epidermis during autolysis based on data from cryofractographic and electron microscopic studies]. AB - The character of the cell membrane component destruction of the human epidermis when kept in a humid camera at 4 degrees or 37 degrees C was studied electron microscopically and by a freezing-chopping method. Intermembranous proteins undergo considerable changes and are more labile than a lipid membranous component. PMID- 1872692 TI - [Effect of a single overheating on kidney ultrastructure]. AB - Large human populations have to live and work under conditions of heat in the arid zones or in industry. It is shown in the experiment, that a single overheating of animals of various duration results in a considerable damage of glomeruli and tubules the clinical manifestation of which is the development of acute renal failure. PMID- 1872693 TI - [Primary nodular lymphosarcoma of the breast]. AB - A case of primary breast lymphosarcoma with axillary lymph node involvement and a local relapse after radical mastectomy has been described. The patient was a 43 year-old woman. Histologically, the primary tumour showed nodular (follicular) growth of prolymphocytes (centrocytes) and lymphoblasts (centroblasts) whereas the lymph node involved and relapsed tumour were characterized by diffuse proliferation of lymphoblasts (centroblasts). Immunocytochemistry revealed B lymphocytic nature of the tumour cells. There were some difficulties in histological interpretation of this tumour due to both artificial structures and so-called lymphoepithelial lesions--remnants of ductal and lobular structures in the tumour tissue. The follicular type of growth of the primary breast lymphosarcoma is not in concordance with the current concept of histogenesis of the mucosa-associated lymphoid tissue lymphomas. PMID- 1872694 TI - [Giant teratoma of the placenta (acardius amorphus)]. AB - This was either giant teratoma of placenta or malformed twin foetus. A premature separation of placenta took place this resulting in an antenatal asphyxia of the second foetus. The mechanical pressure of the tumour could play a role in the development of asphyxia. PMID- 1872695 TI - [Case study of congenital heart defects]. AB - A rare case is presented: at the autopsy in a 54-year-old female patient a congenital heart defect was found in the form of the valve remnants of the embryonal venous sinus (Chiari network and enlarged Eustachian valve). The right atrium thrombosis in the region of Chiari network resulted in the thromboembolism of the left pulmonary artery this being an immediate cause of death. PMID- 1872696 TI - [Familial hypertrophic cardiomyopathy]. AB - Two genetically associated observations of the familial cardiomyopathy in a 34 year-old father and 2-day-old son are described. Verification of the lesions is performed by means of macro-and microscopic analysis including the post-mortem contrast cardioventriculography and histotopographic investigation. Specific changes in the interventricular septum and left ventricle are found in both cases as well as asymmetric hypertrophy and elimination of the cavity of the left ventricle in both father and son. PMID- 1872697 TI - [Pathologic diagnosis]. PMID- 1872698 TI - [Pathologic diagnosis]. PMID- 1872699 TI - [From diagnosis--to the problem of development of a pathology service (concerning the article by D. S. Sarkisov "Diagnosis")]. PMID- 1872700 TI - [Ksav'e Bisha and the science of the New Age]. PMID- 1872701 TI - [The 50th anniversary of the pathology chair of the N. A. Semashko Moscow Stomatologic Institute]. PMID- 1872702 TI - [Liver sinusoidal cells: nature, functional characteristics, and cooperative relationships]. AB - Morphological and functional features as well as cooperative relations of Kupffer's cells, endotheliocytes, lipocytes and pit-cells under normal and pathological conditions delineated in the literature are reviewed. It is shown that liver sinusoid cells protect the parenchyma, control hepatocyte regeneration, take part in the antitumor immunity, participate in the metabolism of lipids, lipoproteins, proteins, biogenic amines and collagen while the cooperative interaction between them and hepatocytes determines an interhepatic homeostasis. PMID- 1872703 TI - [Immunohistochemical study of meconial antigens in neoplasms and mucosa of the colon and rectum]. AB - The expression of 4 meconial antigens--beta-1-MA, beta-2-MA, MMA, gamma-MA in neoplastic and preneoplastic colonic mucosa was studied. Meconial antigens were revealed in small amount in adult normal colonic epithelium. The mucosa adjacent to tumours was rich in these antigens. Cellular localization of meconial antigens in these parts of colonic mucosa was similar to that of embryonal alimentary tract. beta-1-MA was found in 96%, beta-2-MA--73.6%, MMA--82.8%, gamma-MA--31.8% of colonic carcinomas. PMID- 1872704 TI - [Hearts with double inlet ventricle. Morphological aspects in 20 cases]. AB - PURPOSE: The authors intended to verify the most common anatomical presentations of hearts with double inlet ventricle (DIV) and the associated lesions, in order to provide information regarding surgical palliation/correction. MATERIAL AND METHODS: Twenty hearts presenting DIV, from pathological collections. The sequential segmental analysis was applied. RESULTS: Fourteen cases showed usual atrial arrangement, and six isomeric atria (4 with right isomerism and 2 with left isomerism). "Situs solitus" showed two atrioventricular (AV) valves, and the others a single valve. The main ventricle was morphologically left in 13 cases, right in one and of indeterminate morphology in six. The ventriculoarterial connexion was discordant in 10 cases, concordant in two, of double outlet type in eight (6 from an indeterminate ventricle, one from the main chamber and one from the rudimentary ventricle). Pulmonary obstructive lesions were common in the group with atrial isomerism (67%). AV valve stenosis was present in 4 cases, two of the left valve and two of the right one. Straddling of one AV valve was observed in 5 cases and aortic coarctation in three. The ventricular septal defect was restrictive in two cases, both with double inlet to a dominant left ventricle and a concordant AV connexion (Holmes'heart). CONCLUSION: In those with atrial isomerism, the obstructive pulmonary lesions are the dominant feature and require early attention. For the other group, the atriopulmonary anastomosis procedures should take into account peculiarities such as AV valve dysfunctions and aortic coarctation. PMID- 1872705 TI - [Endocavitary fulguration of accessory pathways in the treatment of Wolff Parkinson-White syndrome]. AB - PURPOSE: To show our first experiments with the treatment of Wolff-Parkinson White syndrome through endocavitary fulguration of accessory pathway. PATIENTS AND METHODS: Fourteen endocavitary fulguration sessions applied in 9 patients with the Wolff-Parkinson-White syndrome. Five were men and the average age was 35 years. RESULTS: We obtained complete interruption of the conduction by the anomalous pathway in 7 cases: 4 of them needed only one session and the remaining 3, two sessions. Three fulguration sessions were carried out with the remaining patient (actually the first to be submitted to the treatment), and the procedure in that case proved to be unable to interrupt the conduction by the anomalous pathway. This patient was submitted to surgical ablation. In all cases it was not observed any cardiologic complications due to the application of this technique. CONCLUSION: The endocavitary fulguration of the accessory pathway is a safe and efficient method and must be considered as a first option when the ablation of the anomalous pathways is indicated. PMID- 1872706 TI - [Cardiac manifestations of hyperthyroidism in the elderly]. AB - PURPOSE: To evaluate the cardiocirculatory abnormalities of hyperthyroidism in the elderly. PATIENTS AND METHODS: Twenty-four hyperthyroid patients, 18 women and six men, aged 60 to 87 (average 73.5) years were studied. Seventeen (70.9%) patients had associated cardiocirculatory diseases. The evaluation was made on clinical grounds complemented by electrocardiographic, radiologic, phonomechanocardiographic and echocardiographic examinations. RESULTS: Cardiocirculatory symptoms were observed in 17 (70.9%) patients and congestive heart failure in nine (37.5%) of them. The electrocardiogram was abnormal in 20 (83.3%) patients and the tachyarrhythmias were the commonest abnormality (62.5%). Eight (33.3%) patients had chronic atrial fibrillation and five (20.8%) had sinus tachycardia. There was no significant statistical difference on the electrocardiograms of patients with and without cardiocirculatory abnormalities. Cardiomegaly was significantly more prevalent in hyperthyroid patients, with (64.7%) or without (57.1%) cardiocirculatory abnormalities, than in normal elderly (23.9%). Left ventricular performance was studied in 14 patients through the systolic quotient and was found normal or high in 12 (85.7%). The percentage of fractional shortening (delta D%) was higher than 30 in all patients. None of the patients was found to have symmetric or asymmetric hypertrophic cardiomyopathy and mitral valve prolapse on echocardiogram. CONCLUSION: Hyperthyroidism in the elderly patient determines frequently cardiocirculatory abnormalities that may be misdiagnosed with those caused by the ageing process or by associated cardiopathies. This diagnosis should be suspected in all elderly patients having tachyarrhythmias and/or cardiac failure resistant to usual therapy, mainly in patients without clear cardiocirculatory pathology. PMID- 1872707 TI - [Orthostatic hypotension in elderly inpatients]. AB - PURPOSE: To determine the prevalence of orthostatic hypotension (OH) in elderly inpatients, to identify known risk factors as well as to investigate quality of care given to these patients. PATIENTS AND METHODS: One hundred elderly inpatients aged 60 and over (mean age: 69.2 years), 66 women and 34 men were investigated. We measured supine (after resting for 30 minutes) and one, two, three, four and five minutes standing blood pressures. Orthostatic hypotension was defined as a decrease in systolic pressure of 20 mmHg or more with or without symptoms. The case notes of these subjects were reviewed and the presence of risk factors (diseases and medications associated with OH) was recorded as well as the short of treatment given to these patients. RESULTS: The prevalence of OH was 30% (30 patients); 1/3 had symptoms, one or more known risk factors were found in every patient. Neurogenic orthostatic hypotension was found in 5 patients (5 out of 30 patients). Only one patient with OH was diagnosed (1-30 patients). CONCLUSION: There is a high prevalence of OH in elderly inpatients and its association with various known risk factors. Most patients are not diagnosed and therefore not managed properly. PMID- 1872708 TI - [The circulatory system from Galeno to Rigatto]. PMID- 1872709 TI - [Chagas' disease and tachycardiomyopathy]. PMID- 1872710 TI - [Surgical treatment of dysphagia lusoria]. AB - Two cases of this anomaly, in women (26 and 49 years old), with symptoms of short duration (4 and 3 months) of dysphagia, regurgitation and esophagitis, without loss of weight, are presented. In both, the final diagnosis was made by mean of thoracic aortogram. Esophagoscopy realized only in the first patient, demonstrated the pulsatile esophageal compression. The first patient was operated on through a right cervical incision, made in the anterior border of the sternomastoid muscle. In the second, a partial sternotomy, combined with a right supraclavicular prolongation, was used. In both, the anomalous artery was taken from the aorta and behind the esophagus, and anastomosed to the right common carotid artery. The dysphagia disappeared in the second case, but persisted attenuated, in the first one. Manometric studies realized in the 3rd and 18th months postoperatively demonstrated an aperistaltic segment of the esophagus (between 4 and 7 cm from the superior sphincter). PMID- 1872711 TI - [Congenital left sinus of Valsalva aneurysm]. AB - Two cases of left sinus of Valsalva congenital aneurysm (SVCA), incidentally found are described. The authors call attention on rarity of them, and present new concepts about their morphogenesis and incidence. They also suggested a higher incidence of asymptomatic and undiagnosed cases of SVCA should be considered. PMID- 1872712 TI - [Cardiac rhabdomyomas]. AB - Case report of cardiac rhabdomyoma in one two days old infant with important cyanosis and respiratory insufficiency with evolution to death in few hours. The radiologic feature was a great enlargement of the heart and the electrocardiographic study showed left branch block. The two-dimensional echocardiography study showed multiple intracavitary tumours in both ventricles and in the right atrium. These features were confirmed in the post-mortem study. The microscopic study of the tumors showed proliferation of the spider cells, and vacuolation with the presence glycogen. The diagnosis of cardiac rhabdomyoma was confirmed. The brain and the kidney were not studied for the diagnosis of tuberous sclerosis or kidney tumors. It is very important the early diagnosis by echocardiography, due to the possibility of surgical resection of the intracavitary tumors that cause severe obstruction to the blood flow. PMID- 1872713 TI - [Congenital absence of left pericardium simulating tumor of the anterior mediastinum]. AB - The authors report a case of a patient presenting atypical dyspnea symptom. The physical examination, the chest roentgenogram and EKG were abnormal; the echocardiogram showed an abnormal mass compressing the outflow tract of the right ventricle (RV). These data were confirmed by a computerized tomography. The cardiac catheterization showed a heart deviation to the left and a RV outflow tract gradient of 10 mmHg. Consequently a surgery was necessary. The surgical findings presented an absence of the left pericardium and no tumor was found. This is a rare entity that may be misdiagnosed as other heart diseases but this is the first case in which a tumor of the anterior mediastinum was suspected. PMID- 1872714 TI - [Case 1/91 (Instituto do Coracao do Hospital das Clinicas--FMUSP]. PMID- 1872715 TI - [Syncope: diagnostic possibility and evaluation]. PMID- 1872716 TI - [The future of univentricular hearts]. PMID- 1872717 TI - [Catheter ablation for the treatment of tachyarrhythmias. Fulguration of accessory pathways]. PMID- 1872718 TI - [Catheter ablation of accessory pathways]. PMID- 1872719 TI - [The elderly patient: attention for orthostatic hypotension]. PMID- 1872720 TI - [Nitrate tolerance. Characteristics, determinant factors and preventive procedures]. PMID- 1872721 TI - [Metabolic aspects to consider in essential arterial hypertension]. PMID- 1872722 TI - [Current complications of heart catheterization. Analysis of 100 cases]. AB - PURPOSE: To analyse the impact of the new cardiac catheterization techniques on the complication profile of these procedures. PATIENTS AND METHODS: One thousand consecutive patients who underwent cardiac catheterization from August through December, 1989 (739 diagnostic and 201 therapeutic procedures), who were followed up until hospital discharge. Complications were classified accordingly to their type and severity, and were related to the procedure employed and to the left ventricular ejection fraction. RESULTS: There were no complications in 77.7% of the population studied. In the remaining 236 patients the incidence of mild, moderate and severe complications were, respectively: 11.2%, 7.3% and 3.8%. Severe vascular complications occurred in 0.5%, cardiac perforation requiring emergency surgical repair in 0.1%, severe arrhythmias in 1.4%, acute myocardial infarction in 0.4%, acute pulmonary edema in 0.3% and fatal events in 0.5% patients. CONCLUSION: Despite the increasing application of interventional techniques and the greater number of acutely ill patients referred to cardiac catheterization, these procedures have proved to be safe with a low complication rate. PMID- 1872723 TI - [Nyctohemeral recording of blood pressure and heart rate. Preliminary study]. AB - PURPOSE: A preliminary report is presented of the 24 hour monitoring of blood pressure (BP) and heart rate (HR). PATIENTS AND METHODS: Ten normotensive persons, 5 of each sex with age between 30 and 65 (mean age 41.4) years. The recorder model TM 2420 made by A & D Co. of Japan was used. It has a blood pressure cuff and a recorder that utilized the Korotkoff sounds. It is possible to register the BP with intervals of 1 up to 60 minutes with a circadian division of up to 4 separate periods. A compact analyzer-computer with a printer processing unit prints each recording of PB and HR, the mean value and standard deviation of each period and of the total period of 24 hours. RESULTS: During day time the systolic BP ranged from 96 to 140 mmHg (mean 118.7 +/- 11 mmHg) and the diastolic BP ranged from 67 to 90 mmHg (mean 75.2 +/- mmHg). In the period from 0 to 6 hours AM the systolic BP ranged from 81 to 115 mmHg (mean 102 +/- 13.7 mmHg) and the diastolic BP ranged from 63 to 86 mmHg (mean 67.2 +/- 9.3 mmHg). The mean HR ranged from 75 to 94 beats per minute (mean 84.3 +/- 31). CONCLUSION: This lowering of BP during the night correlates with the variations of plasma nor epinephrine. The main advantages of the circadian monitoring of blood pressure are: 1) to identify the false diagnosis of hypertension based on casual readings; 2) the significant correlation found between prognosis, end-organ-lesion and the pressure load (proportion of BP above normally) or the mean value of BP, while end-organ-lesion and prognosis correlates poorly with casual blood pressure. PMID- 1872724 TI - [Acute reduction of blood pressure: comparative study of nifedipine and clonidine]. AB - PURPOSE: To compare the efficacy of clonidine and nifedipine in rapidly reducing blood pressure (BP). PATIENTS AND METHODS: Forty-four patients with arterial hypertension of any cause were selected and randomly divided in three groups: P group, consisting of 9 patients who received placebo; N group, consisting of 17 patients, 8 males, mean age of 47 years who received 10 mg of sublingual nifedipine; C group, consisting of 18 patients, 6 males, with mean age of 47 years who received 0.2 mg of clonidine per os. The BP were measured on admission and every 15 minutes for 1 hour. The final goal of treatment was to lower diastolic pressure in 20 mmHg or more. RESULTS: At the end of 60 minutes the nifedipine as well as clonidine were equally effective in lowering BP. The earliest manifestation of drug activity occurred at 25 minutes after administration. Side effects were noted only with clonidine in 23% of the cases, but without any clinical significance. CONCLUSION: Nifedipine as well as clonidine are equally effective in rapidly lowering BP with minimal side effects. PMID- 1872725 TI - [Mitral valve prolapse and panic disorder]. AB - PURPOSE: To determine the incidence of mitral valve prolapse (MVP), using echocardiographic and auscultatory criteria, in cases of panic disorder (complicated or not with agoraphobia). PATIENTS AND METHODS: Sixty-five patients (37 women) with panic disorder and without known cardiac disease, mean age 39.8 years (range 19-67) were studied. MVP was diagnosed when there was a typical auscultatory click or when the echocardiographic study (echo) registered one mitral lacinea 2 mm behind the C-D line at the "M" study or a systolic billowing of mitral leaflets in two views to the two-dimensional study. RESULTS: MVP was found in 29 (44.6%) of the patients, 12 (42.7) men and 17 (49.5%) women. A click was found in 19 (24%) of the cases and the Echo was positive in 24 (39.6%) of the patients. Click and a positive Echo finding were identified in 14 patients. CONCLUSION: MVP was found in panic cases, in incidence greater than in the general population. PMID- 1872726 TI - [Primary hyperaldosteronism with angina and arrhythmia]. AB - Case report of primary hyperaldosteronism in a 43 year-old man, with 2 years history of hypertension and cardiovascular involvement manifested by "angina pectoris", ventricular arrhythmia and hypokalemia. The CT scan showed a left adrenal gland adenoma. The patient underwent a surgery for tumor removal, and became asymptomatic during a follow-up period of 11 months. PMID- 1872727 TI - [Apical and inferior mammillary aneurysm in chronic Chagas cardiomyopathy]. AB - A 66 year-old woman with chronic Chagas's heart disease, presented palpitations, dizziness and chest pain. The His bundle electrograms revealed sick sinus syndrome. The left cineventriculography showed apical and inferior aneurysms of mammillary morphological aspect. PMID- 1872728 TI - [Aneurysm of left ventricle associated with post-infarction interventricular communication]. AB - The authors report two cases of left ventricular aneurysm associated with post infarction ventricular septal rupture. This rare association, usually aggravated by high mortality, received successful surgical treatment. PMID- 1872729 TI - [Bayesian analysis of ergometry test]. PMID- 1872730 TI - Inhibition of bovine gingival laminin receptor by bacterial lipopolysaccharide. AB - A laminin receptor was isolated from bovine gingival epithelial-cell membrane. After solubilization with octylglucoside, the receptor was subjected to affinity chromatography on laminin-coupled Sepharose and eluted with cation-free EDTA buffer yielding on SDS-PAGE a 67 kDa protein band. After radioiodination, the protein was incorporated into liposomes which displayed specific affinity towards laminin-coated surfaces, as well as to tooth cementum. The binding of receptor protein to cementum was inhibited by lipopolysaccharide from Bacteroides gingivalis. Preincubation of cementum with the lipopolysaccharide decreased the binding of the liposomal laminin-receptor preparation by 35.8%, while a 59.2% decrease in binding occurred when the lipopolysaccharide was preincubated with the receptor, suggesting that the lipopolysaccharide interfered with the laminin binding site on the receptor. The results demonstrate the existence of a specific gingival cell-surface laminin receptor, show that it is capable of binding to cementum, and provide evidence for the disruption of this process by bacterial lipopolysaccharide. This mechanism may account for the loss of gingival attachment in the pathogenesis of periodontal disease. PMID- 1872731 TI - Immunochemistry and immunogenicity of low molecular weight human salivary mucin. AB - The purposes of this study were to examine the immunogenicity of the low molecular weight human salivary mucin (MG2) and determine its distribution within major and minor human salivary glands. Anti-MG2 sera were produced in Balb/c mice by a variety of immunization schedules. Chromatographically or electrophoretically purified MG2 and partially purified mucin chromatographic fractions exposed to mild denaturing conditions were not immunogenic. Only MG2 without prior exposure to urea or guanidine was able to elicit an immune response. A murine anti-MG2 monoclonal antibody (clone 1/F9) was produced and its monospecificity confirmed by immuno-dot blotting and SDS-PAGE Western transfer. Clone 1/F9 (IgG1; kappa) was of moderate affinity and was directed to a Pronase- and TPCK trypsin-sensitive but periodate-resistant epitope which was not blood group- or sialic acid-specific. Immunocytochemical studies of frozen tissue sections with clone 1/F9 using both indirect and direct methods revealed that MG2 was more heterogeneously distributed within submandibular than labial glands and was not found in parotid or palatine glands. The use of a polyclonal rabbit anti MG2 reagent in either frozen or paraffin-embedded tissues gave the same immunocytochemical results as those obtained with the monoclonal antibody. PMID- 1872732 TI - The effect of airborne lead on lead levels of blood, incisors and alveolar bone of rats. AB - Groups of 20 inbred rats were exposed to: (1) "clean air" (0.05 micrograms Pb/m3) for 70 days; (2) 77 micrograms Pb/m3 for 70 days; (3) 249 micrograms Pb/m3 for 28 days; and (4) 1546 micrograms Pb/m3 for 50 days. Half the rats in each group were then killed and the other half kept in "clean air" until the blood lead of groups 1-3 had returned to normal. That half of the incisors which had been completely renewed during the experimental period, as well as the alveolar bone of each rat, were analysed for lead by atomic absorption spectrophotometry. In the rats killed immediately after exposure, the lead levels by atomic absorption alveolar bone showed significant differences (p less than 0.05) among all four groups, except between groups 2 and 3, indicating the importance of the combined effect of airborne lead concentration and length of exposure. For blood, significant differences (p less than 0.05) were found among all groups. For the post-exposure rats, the incisors and blood showed no significant differences (p greater than 0.05) among groups 1, 2, and 3. For alveolar bone, significant differences were not found (p greater than 0.05) between groups 2 and 3. It can be concluded that during lead exposure the alveolar bone transformation was the highest and that of incisor tissue just lower, and that blood lead became supplemented through the process of remobilization from alveolar bone, as reported for other bones. PMID- 1872733 TI - The effect of lead acetate on dentine formation in the rat. AB - The intravenous injection of lead acetate produces a response in dentine by formation of the so-called lead line. This is associated with a rapid but temporary rise in serum calcium and phosphorus. Previous studies have suggested that lead replaces calcium and phosphorus in the apatite lattice. In this study the lead line was investigated in the scanning electron microscope using backscattered electron imaging and was shown to consist of continuous hypomineralized interglobular spaces within the dentine. Dentine formation was disrupted for at least a week after injection of lead ions. With energy dispersive analysis by X-rays, no localized concentration of lead was detectable within the 'lead line'. It is suggested that the lead line results from a direct effect of lead on the odontoblasts and other hard tissue-forming cells producing a rapid loss of intracellular calcium temporarily displaced by lead ions and a subsequent disturbance of local calcium metabolism. PMID- 1872734 TI - Distribution of fluoride in sound and periodontally diseased human cementum. AB - Fluoride distribution was investigated by an abrasive micro-sampling technique. The fluoride concentration increased with age in both sound and diseased cementum. In sound teeth, the fluoride profiles (distribution of fluoride from the surface to interior) of the middle and apical cementum were similar. In the diseased cementum the profile of the middle region tended to be more variable than that of the apical cementum, suggesting a possible effect of the oral environment on the fluoride profile at this site. PMID- 1872735 TI - Quality assurance education: towards the year 2000. PMID- 1872736 TI - Report on seminar: 'designing care'. AB - The seminar was held under the auspices of the National Demonstration Project, which is a combined effort of the Juran Institute and the Harvard Community Health Plan (HCHP). About 60 delegates attended the conference. Most were from the United States, the rest were from Canada, the Netherlands, the United Kingdom and Australia. The seminar was aimed at introducing those attending to the topic of clinical algorithms. The algorithms were presented as part of a total quality management process concerned with clinical decisions. Algorithms are designed as a pattern, or a map, of a clinical process. It is the aim of an algorithm to ensure stability in a clinical process and to enhance the quality of care given by the process. The seminar was a combination of general sessions and workshop sessions. The general sessions were managed by presenters who had considerable experience in the development of algorithms, and the same presenters then chaired the separate workshop sessions on a group basis. The workshop sessions concentrated on the simulation of algorithm development at the institutions of the attendees. PMID- 1872737 TI - The asthma clinical score and oxygen saturation. AB - A clinical estimate of asthma severity using a clinical score and oxygen saturation measurements by pulse oximetry was carried out on a group of 41 children aged 3 years or older. The measurements were performed at the time of each child's admission to hospital with an acute asthma attack. The correlation coefficient (r) between the asthma score and the oxygen saturation was -0.76. For children older than 3 years, clinical scoring methods may have a place in the assessment of those with acute asthma, especially when they are receiving high flow oxygen treatment. PMID- 1872738 TI - Quality assurance. AB - Modern health care is changing--we have more chronic disease, increasing demands for documentation from government and legal bodies, and greater emphasis on disease screening and prevention. Quality assurance is important in developing health care services to meet these changing needs because it provides standards by which we can measure the activities involved in the delivery of health care, and quality assurance programmes are more likely to ensure that the predefined standards of health care are being met. This paper provides: (i) an acceptable definition of quality assurance (QA); (ii) an explanation of why we need it; (iii) evidence that the medical decision-making process is failing under the modern technological advances; and (iv) guidelines for meeting future health care standards by using the modern technological tools of computers and computer software to support the beleaguered clinical decision-making process. PMID- 1872739 TI - Quality and health care: future directions for health care quality management. PMID- 1872740 TI - Parent satisfaction survey: paediatric physiotherapy services. AB - The aims of the survey were: to obtain data on children being seen in the department in order to determine whether the needs of parents and children are being met; to discover parents' attitudes to 'parent-based' treatment; and to establish whether physiotherapists' expectations of what parents can do at home are realistic. A parent satisfaction survey was developed and sent to outpatients who had attended the physiotherapy department in the previous 6 months. Results were collated and analysed in the areas of: referral source; appointments; treatment; and general opinion. The results are reported in detail and discussed. Results are generally positive and indicate that the physiotherapists are catering for the needs of parents and children, and have appropriate ideas of what can be achieved at home. Several areas of potential improvement are identified and discussed. PMID- 1872741 TI - Commentary on a national invitational seminar on quality assurance in health services. AB - This paper is a slightly modified version of a paper presented at a quality assurance seminar at Royal North Shore Hospital, Sydney on 7 December 1990. The paper uses the seminar given by Professor Avedis Donabedian in Sydney 13-17 August 1990, to emphasize two issues. First, while there are claims from many hospitals that they are conducting quality assurance, such activity demands the use of explicit criteria in one form or another and, in the author's view, few if any hospitals are, in fact, using this technology. What, then, of their claims to be conducting quality assurance? The second point is that Australian efforts at quality assurance have been focused on projects, ignoring the need for a program or system in the hospital, and a program or system is essential if efforts at ensuring effective quality assurance are to succeed. PMID- 1872742 TI - Quality assurance and general practice in Australia. AB - The initiation of a Quality Assurance (QA) Programme for general practitioners in Australia was initiated in 1987. It has had to meet the challenges of a diverse and independent group, but participation has been good after the first three years. The theoretical basis for the types of QA activity undertaken is discussed, as well as the political climate under which general practice QA is being established in Australia and abroad. PMID- 1872743 TI - Peri-operative care for oesophagectomy patients. AB - The aim of this study was to evaluate factors relevant to morbidity and mortality in 54 patients undergoing oesophagectomy at Royal Newcastle Hospital between 1985 and March 1989. There was a high incidence of concurrent medical problems. Significant anaesthetic complications occurred in 6 patients. There were 16 serious general medical complications and 10 surgical complications. Respiratory complications included basal collapse (19), sputum retention (6), pulmonary oedema (2), pleural effusion/haemothorax (5), and severe aspiration syndrome (5). Seven patients required mechanical ventilation for more than 3 days. Two deaths occurred postoperatively. As a result of this audit, changes have occurred in patient selection, management of chylothorax, epidural analgesia and timing of tracheal extubation. PMID- 1872744 TI - St Vincent's Hospital: a case study. Quality improvement programme in the Division of Corporate Services. PMID- 1872745 TI - The evolution of quality assurance in clinical chemistry: a personal view. PMID- 1872746 TI - OsteoPPPorosis--prevention, prevention and prevention. PMID- 1872747 TI - Emergency coronary artery bypass surgery following coronary angioplasty- favourable medium term outcome after eight years' experience. AB - The clinical characteristics, perioperative complications and medium term outcome were analysed for patients undergoing emergency coronary artery bypass surgery (CABG) following failed coronary angioplasty (PTCA). Seven hundred and twenty PTCAs were performed from June 1981 to June 1989, of which 30 (4.2%) resulted in CABG within four hours of PTCA. The perioperative course and follow-up were compared to 30 patients undergoing elective CABG, matched retrospectively for age, sex, month of operation and number of grafts. The emergency group had a tendency to more post operative bleeding, but no increased incidence of early reoperation for bleeding, and had a high incidence of periprocedural Q wave infarction (20% vs 3%, p less than 0.05). The emergency group had shorter bypass time and decreased use of the internal mammary artery (7% vs 50%, p less than 0.05). There was one in-hospital death in the emergency group. At medium term follow-up (3.4 +/- 2.4 years, range two months to eight years) there was one late death in each group, and seven patients in each group had return of angina or congestive heart failure. Twenty-one patients in the emergency group and 22 patients in the elective group were asymptomatic on no cardiac medications. We conclude that patients with failed PTCA requiring emergency CABG are more likely than an elective group to have post operative bleeding but no increased risk of early reoperation, and have a higher incidence of perioperative Q wave infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872748 TI - Home oxygen therapy: an audit of survival. AB - A retrospective audit of the medical records and respiratory function data of 186 subjects placed on long term continuous home oxygen therapy between 1979 and 1988 was undertaken. Kaplan-Meier survival curves were constructed for subjects with Chronic Obstructive Airways Disease (COAD) and Interstitial Lung Disease (ILD). There was an almost twofold greater mortality rate for COAD subjects at 12 months when compared to the Medical Research Council Working Party (MRC) and the Nocturnal Oxygen Therapy multicentre clinical trials (NOTT). However, the mean values of the baseline physiological parameters were similar to these major studies of long term oxygen therapy. Survival of ILD patients was significantly less than COAD patients (p less than 0.001). Within both disease categories, females survived significantly longer than males. Within the COAD category the observed sex difference was not abolished when the data was controlled for age, Pco2, Po2 and pack-years (as an estimate of total cigarette consumption). However, prior smoking history appeared to modify the male-female difference in COAD survival. These are the first Australian survivorship data for patients on long term oxygen therapy. The more adverse survival figures compared with the overseas studies may reflect the co-existence of other diseases. PMID- 1872749 TI - Wheat dust-associated respiratory disease in a farming community. AB - Sixty-six volunteers who considered themselves to have wheat dust-related respiratory disease, were reviewed from a farming community. A spectrum of disease was described ranging from a mild allergic rhinitis limited to periods of wheat dust exposure through to perennial asthma in which wheat dust was but one of several precipitating factors. Approximately half of those with asthma had symptoms limited to times of wheat dust exposure. Results of a limited survey of farmers showed patterns of symptoms similar to those in the volunteer group. Most subjects were atopic with elevated IgE levels, and had positive skin prick tests to environmental allergens. All but one of 65 subjects tested had a positive RAST test to wheat dust antigen. It is concluded that wheat dust associated respiratory tract disease is a significant problem in Australian farming communities, that a particular pattern of asthma can be described, and that IgE mediated reactions contribute to this disease pattern. PMID- 1872750 TI - Monoclonal immunoglobulin bands in the cerebrospinal fluid. AB - Isoelectric focusing and immunofixation allow the detection of abnormal immunoglobulin bands in the cerebrospinal fluid (CSF). In normal subjects, the immunoglobulins in the CSF are derived from serum. In inflammatory disorders of the nervous system, there may be intrathecal immunoglobulin synthesis usually seen as oligoclonal bands confined to the CSF. Monoclonal immunoglobulin bands in the CSF are not common. We surveyed 1490 CSF samples, and found that a total of nine had a monoclonal immunoglobulin band and that in three this was not present in the serum. Of these three, one patient had chronic inflammatory demyelinating polyneuropathy and the antibody may have been secreted by lymphocytes which had infiltrated the nervous system. The other patients had either lymphoma or lymphomatoid granulomatosis within or adjacent to the nervous system and the monoclonal immunoglobulin was probably secreted by B lymphocytes within those lesions. PMID- 1872751 TI - Long-term nasal CPAP does not ameliorate obstructive sleep apnoea. AB - Fifty-seven patients with obstructive sleep apnoea (OSA) were treated for at least six months with nasal continuous positive airway pressure (CPAP). At follow up, sleep studies were performed in which CPAP was not used for the first half of the night. We compared the severity of OSA at follow-up without CPAP to the severity of OSA during the patient's initial diagnostic study. Apnoea and hypopnoea index (AHI) fell from 41.4 +/- 7.5 (mean +/- 95% CI) to 34.8 +/- 7.9 (p = 0.06 by Wilcoxon test) and minimum oxygen saturation rose from 71.6 +/- 3.2 to 78.5 +/- 2.6 (p less than 0.001). Some of this change may have been due to reduced REM sleep in the follow-up study (10.5 +/- 2.1% Total Sleep Time vs 7.4 +/- 2.4% TST, p less than 0.05). Long-term nasal CPAP was not associated with any reduction of obesity (BMI before CPAP 31.9 +/- 1.0, after CPAP 31.7 +/- 1.0 (p = 0.39). Systolic arterial pressure fell (before CPAP 143.0 +/- 4.5 mmHg, after CPAP 136.3 +/- 4.6, p less than 0.05) but diastolic pressure did not (before CPAP 88.5 +/- 3.0 mmHg, after CPAP 85.6 +/- 2.9 mmHg, p = 0.11). We concluded that the effect of CPAP treatment for six or more months was a small fall in AHI and a small rise in minimum SaO2, but that this would be of marginal clinical significance, and may be artefactual. PMID- 1872752 TI - Permanent junctional reciprocating tachycardia misdiagnosed as 'cardiomyopathy'. AB - In a nine-year-old female, cardiac failure was erroneously attributed to idiopathic cardiomyopathy and cardiac transplantation was planned. The actual cause of cardiac failure was permanent junctional reciprocating tachycardia (PJRT), a rare form of supraventricular tachycardia. The diagnostic error was discovered before transplantation was performed and the arrhythmia was treated surgically. This resulted in return of near normal cardiac function. PMID- 1872753 TI - XY female athlete with Olympic potential. AB - We report a 16-year-old phenotypic female with XY pure gonadal dysgenesis. A dysgerminoma was found in one of the dysgenetic gonads stressing the importance of prophylactic gonadectomy. Her case presents a difficult problem because as a member of a national junior training squad, she had the potential for competing at international level where her genetic sex could be a profound liability. PMID- 1872754 TI - Complete response of a transitional cell carcinoma of the renal pelvis to leucovorin/5 fluorouracil chemotherapy. AB - A 56-year-old female underwent treatment with leucovorin and 5-fluorouracil for extensive metastatic moderately differentiated transitional cell carcinoma (TCC) of the renal pelvis. This resulted in a complete response for 20+ months. This combination has not been reported before in TCCs of the urinary tract and requires further exploration. PMID- 1872755 TI - Salmonella empyema in a patient with lymphoma. AB - Salmonella empyema occurred in a patient with non-Hodgkin's lymphoma. He was successfully managed with a combination of antibiotics and surgery. PMID- 1872756 TI - Optic disc oedema and diabetes mellitus: a case report with review. AB - Optic disc oedema is a neurological complication of diabetes mellitus. Typically, the patient is a young diabetic with minimal symptomatology but severe bilateral optic disc oedema discovered on routine eye examination. It is a relatively benign condition which on occasion can result in a residual visual deficit, but requires no specific intervention and represents a subgroup of anterior ischaemic optic neuropathy (AION). We present a patient with insulin dependent diabetes and asymptomatic bilateral optic disc oedema, with a brief review of the syndrome and its pathogenesis. PMID- 1872757 TI - Diclofenac hepatitis. AB - We report five cases of biopsy-proven hepatitis developing between six and 20 weeks after administration of diclofenac. In one patient jaundice had previously developed following use of ibuprofen. In another the clinical, biochemical and histopathological features were those of chronic active hepatitis and treatment with corticosteroids was required. All patients recovered from their liver injury without sequelae. Resolution of symptoms occurred between three and 12 weeks following cessation of the drug, while liver function tests returned to normal between seven and 16 weeks after drug withdrawal, except in the patient with chronic active hepatitis who remained biochemically abnormal for eight months. Three of the five patients developed transient circulating autoantibodies, suggesting immune mechanisms may be important in the pathogenesis of this injury. The incidence of severe hepatic dysfunction related to the use of diclofenac appears low and is probably in the order of one case per 50-100,000 prescriptions. PMID- 1872758 TI - Pregnancy-induced hypertension: pathogenesis and management. PMID- 1872760 TI - The Lambie-Dew oration. PMID- 1872759 TI - Osteoporosis and calcium. PMID- 1872761 TI - Problems with nasal CPAP machines. PMID- 1872762 TI - Ischaemic ... or hypoxic hepatitis. PMID- 1872763 TI - Cyclosporin associated remission in severe aplastic anaemia. PMID- 1872764 TI - Urinary oestriol assay for monitoring fetoplacental function. AB - During the years 1971-1984 urinary oestriol excretion was tested in 51,427 patients (group 1). One or more low oestriol value was found in 10.7% of patients; in this group the stillbirth rate was 6.8 times higher, the neonatal death rate 3.8 times higher, and fetal growth retardation rate 3.5 times higher than in patients with normal oestriol values (all p less than 0.00001). During the years 1985-1989 a further 20,635 patients were tested (group 2) and 7.6% had one or more low oestriol value. The perinatal mortality rate in patients with normal oestriol excretion fell from 0.8% in group 1 to 0.5% in group 2 (p less than 0.005), and in patients with low oestriol excretion from 4.2% in group 1 to 2.4% in group 2 (p less than 0.002). However, patients in group 2 with low oestriol values still had significantly unfavourable results, compared to those with normal oestriol values--stillbirth rate 3.3 times higher, neonatal death rate 4.6 times higher, and fetal growth retardation rate 3.2 times higher (all p less than 0.00001). Intravenous dextrose and aminoacid infusions were given to 967 patients who had persistently low oestriol values in spite of rest in hospital, in an attempt to correct fetoplacental function; the perinatal mortality rate was 0.9% in the 660 (68.3%) who responded favourably, and 9.8% in the 307 (31.7%) who did not respond (p less than 0.0001). PMID- 1872765 TI - Ponderal index: a better definition of the 'at risk' group with intrauterine growth problems than birth-weight for gestational age in term infants. AB - A study was undertaken at Nepean Hospital, Penrith to compare the outcome of pregnancies with growth retarded infants; 2,508 consecutive births were analyzed between August 1, 1989 and April 30, 1990. A comparison of outcome was made between infants whose birth-weight for gestational age was below the tenth percentile and infants who had a low ponderal index from 37 weeks' gestation. The Caesarean section delivery and fetal distress rates were significantly higher for infants with a low ponderal index than for infants with a low birth-weight. Ponderal index appears to be a better measure of infants with intrauterine growth problems than birth-weight percentiles. PMID- 1872766 TI - HELLP syndrome: an often unrecognized complication of preeclampsia. AB - We describe a case of preeclampsia with the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and highlight the delayed diagnosis due to its nonspecific presentation. This syndrome is associated with significant maternal and perinatal mortality and morbidity and we discuss the importance of early recognition of the condition, aggressive management and a multidisciplinary approach. PMID- 1872767 TI - Transabdominal chorion villus sampling: a safe and reliable procedure. AB - A complete follow-up of the first 578 patients undergoing transabdominal chorion villus sampling (TACVS) in our combined practices was undertaken to determine the pregnancy loss rate. Factors contributing to losses and the problems incurred in achieving a clinically relevant result were also examined. It was found that increasing experience led to fewer procedural difficulties but that there persisted a higher problem rate in those women with a retroverted uterus. In 98.1% of patients an adequate volume of tissue was obtained and in 95.5% a clinically relevant result was achieved. This second figure rose to 96.3% in the latter part of the study. There was a total fetal loss rate of 2%, with only 0.5% (3 patients) having a missed abortion within 4 weeks of the procedure. It is concluded that TACVS is a reliable procedure with a high level of safety. PMID- 1872768 TI - Evaluation of plasma fructosamine as a screening test for gestational diabetes. PMID- 1872769 TI - Doppler flow velocity waveform analysis in postdate pregnancies. AB - This study examines the efficiency of Doppler flow velocity waveform analysis in the evaluation of the postdate pregnancy. Seventy women whose pregnancies were at or beyond 41 weeks' gestation were assessed by calculating the systolic/diastolic ratios from umbilical and uteroplacental arteries. Waveform ratios from pregnancies associated with fetal compromise and abnormal neonatal outcome were similar to those from pregnancies in which the outcome was normal. These findings indicate that the pathophysiology of placental insufficiency in postdate pregnancies differs from that observed in cases of fetal growth retardation at earlier gestational ages. Doppler flow velocity waveform analysis is unlikely to be of benefit in the routine assessment of the postdate pregnancy. PMID- 1872770 TI - The second stage of labour: durational dilemmas. AB - The optimal management of prolonged second stage of labour remains a confused area of thought and action. This confusion is particularly evident when epidural analgesia is also being used. A review of the literature indicates that prolonged duration of the second stage, i.e. from full dilation of the cervix until delivery, with or without epidural analgesia, has little adverse effect on perinatal outcome. More attention should be paid to the expulsive phase of the second stage and greater efforts made to reduce unnecessary interventions. PMID- 1872771 TI - Rupture of the pregnant uterus--a 21-year review. AB - Uterine rupture is still a common problem in developing countries although even here the incidence varies from urban to rural settings. This article is a review of uterine rupture in an urban referral hospital in Malaysia. It examines aetiology, clinical presentation, complications and management of the problem. Meticulous screening of patients together with optimal antenatal and intrapartum care will markedly reduce the incidence of uterine rupture. Early diagnosis and prompt treatment will further help reduce morbidity and mortality to both mother and fetus. PMID- 1872772 TI - The impact of multiple induced abortions on the outcome of subsequent pregnancy. AB - The obstetric outcome of 285 women with a history of previous multiple induced abortions is compared to that of 285 age matched primigravidas. In the study group, 219 women had 2 previous induced abortions and 66 had 3 or more, the maximum number being 8. There was a higher incidence of unmarried women and smokers in this group but a lower incidence of uneducated women. There was no difference in the incidence of antenatal complications between the 2 groups. The mean gestation at delivery, duration of labour and mode of delivery were comparable. There was an increased incidence (p less than 0.01) of retained placenta in the subgroup of women with 3 or more previous induced abortions. There were no maternal or perinatal deaths. The mean birth-weight was comparable and there were no infants weighing less than 1,500 g in either group. We conclude that multiple previous induced abortions appear to have minimal impact on the obstetric outcome of subsequent pregnancy in this population, and in the absence of other risk factors there is no need to alter standard obstetric management in this group of women. PMID- 1872773 TI - The use of 16.16-dimethyl-PGE1-delta-methyl ester (Cervagem) vaginal pessaries for cervical dilatation prior to evacuation for second trimester termination. AB - The results of a study of 101 consecutive second trimester terminations by Dilatation and Evacuation (D & E) under ultrasound control is presented. All had a Cervagem pessary inserted into the vagina prior to the procedure. The PGE1 analogue was assessed as 'effective' in 97% of patients. Concomitant ultrasound resulted in no patient leaving the operating table with retained products. The high efficacy of the single pessary associated with a low incidence of side effects makes this combination the method of choice for nearly all second trimester terminations. PMID- 1872774 TI - Second trimester abortion by extra-amniotic PGF2 alpha infusion: experience of 178 cases. AB - There is a continuing need for second trimester induced abortions, most recently due to the increase in the use of antenatal diagnostic procedures, amniocentesis, high resolution ultrasound and cordocentesis. To evaluate the efficacy and safety of extraamniotic infusion of PGF2 alpha for this purpose a retrospective review of 178 procedures was undertaken. There were 4 failures of the technique and the major complication rate was 5.6%. This rate was independent of gestational age. The mean induction to abortion interval was 29.6 (+/- 16.3) hours. The conclusion reached after comparison with other published data is that extraamniotic PGF2 alpha infusion is a slow and painful but safe and effective technique, but that at gestational ages less than 17 weeks, a comparative trial of Dilatation and Evacuation versus extraamniotic PGF2 alpha infusion would be justified. PMID- 1872775 TI - Obstetric training for rural general practice. AB - In the current debate on the problems faced by rural doctors, lack of training in procedural disciplines such as obstetrics has emerged as a priority issue. With specialist obstetric services concentrated in metropolitan and major provincial cities, general practitioners will continue to provide rural communities with obstetric care. Postgraduate obstetric training programmes for general practitioners must provide procedural skills training for intending rural practitioners or risk being regarded as irrelevant to the needs of rural communities. PMID- 1872776 TI - The embryo comes of age: the first decade of the Fertility Society of Australia. AB - The Fertility Society of Australia was conceived in 1980 and born in 1982. After 10 years its history and achievements are reviewed. PMID- 1872777 TI - Can ultrasonography reliably predict the occurrence of multiple pregnancies in gonadotrophin ovulation induction? AB - A retrospective study of 78 patients with 106 stimulated conception cycles after successful gonadotrophin ovulation induction was made to analyze the relationship between the sizes and numbers of ovarian follicles seen on ultrasound and the eventual number of conceptions that resulted in each cycle. Fifteen cycles (14.2%) resulted in spontaneous abortions. There were 58 singleton pregnancies (54.8%), 26 sets of twins (24.5%), 6 sets of triplets (5.6%) and 1 set of quadruplets (0.9%). In 86 cycles with the last scans performed shortly before the ovulating dose of HCG, 3 or more mature follicles were found in 50 (58%). These cycles resulted in 31 (62%) singletons, 16 (32%) twin pregnancies and 3 (6%) triplet pregnancies. Pregnancies resulted even when there were no 'mature' follicles seen on scan. No statistical correlation was found between plurality of pregnancy and size or number of follicles, or oestradiol excretion on the day the ovulating dose of HCG was given, although high-order multiple pregnancies were more likely if the oestrogen excretion was more than 200 ug/24 hours (p = 0.001). The dosage of HCG correlated inversely with the occurrence of multiple pregnancies (p = 0.02). In conclusion, neither oestrogens nor ultrasonography could accurately predict multiple conceptions in gonadotrophin stimulated cycles. PMID- 1872778 TI - Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia. AB - A series of 45 ovulatory women with a complaint of menorrhagia were randomized into 3 treatment groups, before receiving therapy with mefenamic acid in 2 cycles and 1 of 3 other agents in 2 cycles: naproxen (group 1; n = 14), a low dose monophasic combined oral contraceptive (group 2; n = 12) or low dose danazol (group 3; n = 12). Menstrual blood loss was measured in 2-4 control cycles and during therapy. Mefenamic acid reduced measured blood loss by 20%; 38%; and 39% in groups 1-3 respectively. Naproxen reduced blood loss by 12%; the oral contraceptive by 43%; and danazol by 49%. There was no statistically significant difference in blood loss reduction (mean of 2 cycles) between any of the treatments, although women on danazol experienced a dramatic and highly significant further reduction in blood loss after the first treatment cycle (p less than 0.003). These were all effective therapies in a majority of women, but some 'non-responders' were seen in each group. The 'non-responders' had a significantly lower pretreatment blood loss than responders. Several women in group 1 showed anomalous responses to prostaglandin inhibitors with consistent and substantial exacerbation of menorrhagia during therapy. A number of reasonable therapies exist for the medical treatment of menorrhagia, but because none is suitable for everyone management needs to be individualized for each patient. PMID- 1872779 TI - Intrauterine surgery--a new era. PMID- 1872780 TI - Presacral neurectomy--a reappraisal. AB - Between April 1984 and April 1990, 20 patients with a mean age of 27.9 years underwent presacral neurectomy at The Royal Women's Hospital, Melbourne, Australia. Overall, 11 of the 19 patients (58%) assessable for follow-up were totally cured of pain and 8 (42%) were partially cured. The most common indication for presacral neurectomy was secondary dysmenorrhoea, usually in association with endometriosis or pelvic adhesions. In 4 patients with uterine dysmenorrhoea not associated with pelvic pathology the operation produced a complete cure. The general consensus of gynaecological opinion is that presacral neurectomy should still be reserved for a limited number of carefully selected patients in whom other methods of treatment have been exhausted. It is imperative that a prior psychological assessment should be undertaken whenever a functional component is suspected. Whilst pain of uterine origin may be cured by presacral neurectomy, lateral pelvic pain of adnexal origin requires ovarian sympathectomy. PMID- 1872781 TI - Determinants of maternal mortality in the developing world. AB - Maternal mortality is the culmination of a series of detrimental events in a woman's life, pregnancy being the last one. The underlying pathology is the lack of education, sanitation, accessible health care, as well as poor nutrition and poverty. These affect women during pregnancy and childbirth when they are more vulnerable. This 10-year review of literature from the developing world focuses on, and discusses the determinants of maternal mortality. Methods of reducing maternal mortality through policy addressing health care needs are touched on. PMID- 1872782 TI - Was that hysterectomy really necessary? Audit of operative justification at the Aga Khan University Medical Centre, Karachi. AB - Hysterectomy in Pakistan, like in other parts of the world is considered to be overused in a number of cases. As a part of a quality assurance process at the Aga Khan University Medical Centre, Karachi, 376 hysterectomies performed between January, 1987 and December, 1989 were retrospectively analysed and the results are presented. In 250 (66.5%) cases, where pathology was expected to be found, the hysterectomy was considered justified if the preoperative diagnosis was verified by the pathology report of if significant alternate pathology was present. In 126 (33.5%) cases, where no pathology was expected to be found 'validation criteria' were used to ascertain justification of the procedure. The results showed justification rates of 83% for recurrent uterine bleeding, 85% for adenomyosis, 90% for adnexal masses and endometrial carcinoma, 95% for fibroids, 97% for pelvic relaxation and 100% each for pregnancy catastrophe, endometriosis, chronic pelvic inflammatory disease and premalignant disease of uterus and cervix. In general 92.0% of all hysterectomies in this series were justified. PMID- 1872783 TI - Complications and bilaterality of mature ovarian teratomas (clinicopathological evaluation of 286 cases). AB - Bilaterality, complications and associated pathology were reevaluated in 286 cases of mature teratoma of the ovary, treated in the last 25 years. Torsion was the most frequent complication, occurring in 22 (7.7%) patients. Rupture, infection and secondary malignant change were uncommon complications, occurring in 11 (3.8%), 7 (2.4%) and 1 (0.3%) patients, respectively. Both ovaries were evaluated histologically in 226 patients, 31 (13.7%) of whom were shown to have bilateral tumours, including 2 patients with tumour in the normally appearing ovary, contralateral to the gross tumour. PMID- 1872784 TI - Primary adenocarcinoma of the uterine cervix: changing clinical profile. PMID- 1872785 TI - Pelvic lymph node metastases in early invasive carcinoma of the cervix- histopathological 'risk' factors. AB - Histopathological features in 89 cases of Stage 1B and early 2A invasive carcinoma of the cervix who underwent Wertheim radical hysterectomy and pelvic lymphadenectomy were studied. Depth of tumour invasion and lymphatic/vascular space permeation by tumour cells were significantly associated with lymph node metastases. The other features such as tumour type, and stromal leucocytic reaction showed no significant relationship to the presence of lymph node metastases. PMID- 1872786 TI - Rupture of a splenic artery aneurysm in pregnancy. PMID- 1872787 TI - Malignant hyperpyrexia and sudden infant death. PMID- 1872788 TI - Caudal analgesia by the obstetrician. PMID- 1872789 TI - Aerospace Medical Association. Directory issue. PMID- 1872790 TI - [Possibilities and limits of immunodiagnosis of strongyle infections in horses]. AB - In an investigation period over 8 months the natural course of infection was studied by means of coproscopic and serological methods in 27 mares and 29 foals. The examination of the stool showed in mares, before the beginning of the grazing season, an infection rate of 100% with small and a rate of 7.4% with large strongyles (Str. vulgaris). Serologically the ELISA showed in foals only a distinct increase of antibody activity with the somatic antigen. The mares retained the high IgG-values of activity, which were already found at the beginning of the investigations. Even though the agglutination test can be applied for control of the effectiveness of therapy in a horse population, individual diagnostic possibilities remain limited. This is due to the reduced sensitivity and specificity of the IgG(T)-concentration under natural conditions of infection. The double-antibody-sandwich-ELISA technique has shown to be basically feasible as a test for antigens from small strongyles. Somatic antigen could most sensitively be demonstrated by antibodies to ES-antigen, ES-antigen, however, by antibodies against somatic antigens. PMID- 1872791 TI - [Parasite fauna of red foxes in Berlin (West)]. AB - The infestation with ecto- and endoparasites of red foxes in Berlin (West) was investigated. As shown by post mortems of 100 animals (47 males and 53 females), none of them was found to be free of parasites. With regard to ectoparasites, 3 species of ixodes ticks, 7 flea species, one species of biting lice and mite species were demonstrated. The sarcoptic mange is often inducing the death of the foxes and is considered to be a limiting factor of the population increment. Concerning endoparasites, cestodes (6 species), trematodes (7 species), nematodes (10 species) and 3 coccidian species were found. The infestation rate with different species of hook worms, ascarids and mesocestoides was remarkably high. However, none of the foxes were infected with Trichinella spiralis or Echinococcus multilocularis. As shown by ELISA, in 15% of foxes antibodies against Borrelia burgdorferi were found. Therefore, the red fox must be considered as a reservoir host for Lyme-borreliosis. PMID- 1872792 TI - [Salmonella enteritidis in chicken eggs]. AB - After an outbreak caused by salmonella enteritidis (SE) of which home-made mayonnaise and remoulade sauce were found to be the cause, SE was detected in ten of the remaining eggs. Subsequently 409 eggs of the next shipment from the same outlet were examined bacteriologically. Of 70 of the eggs examined, SE was found in 5 egg yolk samples and in 3 egg white samples as well as in 2 of 7 pooled shell samples. Five out of 35 pooled whole egg samples comprising a total of 349 eggs were likewise positive for SE. The isolates belonged to the phage types 4 and 7 carried the virulence plasmid pRQ29. PMID- 1872793 TI - [Possibilities of clinico-cytological diagnosis in contagious equine metritis (CEM)]. AB - Clinical, bacteriological and serological examinations on a 6 years old pony mare were performed. Cytological alterations in the genital tract were also recorded. A cellular reaction was seen after infection with T. equigenitalis. This reaction is an evidence for infection but it is not specific for this organism. Cytological studies should be performed on mares especially in cases of latent infections to complete bacteriological examination and to prevent false positive or negative results. PMID- 1872794 TI - Monoclonal antibodies specific for the C-terminus of the laminin B2 subunit. Evidence for glycosylation differences between murine and human laminin. AB - We have raised a panel of monoclonal antibodies against a beta-galactosidase fusion protein (XLB2.1) containing the C-terminal 153 amino acids of the murine laminin B2 subunit. Five of the nine antibodies characterized recognize human placental laminin as well as murine Engelbreth-Holm-Swarm (EHS)-tumour laminin. Only two of the antibodies recognize both rat parietal-yolk-sac laminin and murine EHS-tumour laminin. Two antibodies recognize an epitope on the human laminin B2 subunit which is masked by N-linked oligosaccharide in murine EHS tumour laminin. These antibodies also fail to bind to laminin from adult-mouse tissues. These results demonstrate a species-specific difference in the glycosylation of the laminin B2 subunit. PMID- 1872795 TI - Modulation of maximal glycogenolysis in perfused rat liver by adenosine and ATP. AB - Rat livers perfused at constant flow via the portal vein with dibutyryl cyclic AMP produced glucose equivalents at a steady maximal rate (6 mumol/min per g of liver). Addition of adenosine (150 microM) caused a biphasic effect. (i) First, the glycogenolytic rate rose transiently, to a mean peak of 150% of control levels after 2 min. This glycogenolytic burst was reproduced by two P1-receptor agonists, but not by ATP, and was blocked by a P1-antagonist (8 phenyltheophylline), as well as by inhibitors of eicosanoid synthesis (indomethacin, ibuprofen or aspirin). It did not occur in phosphorylase-kinase deficient livers. The adenosine-induced glycogenolytic burst coincided with moderate and transient changes in portal pressure (+6 cmH2O) and O2 consumption ( 20%), but it could not be explained by an increase in cytosolic Pi, since the n.m.r. signal fell precipitously. (ii) Subsequently, the rate of glycogenolysis decreased to one-third of the preadenosine value, in spite of persistent maximal activation of phosphorylase. The decrease could be linked to the decline in cytosolic Pi: both changes were prevented by the adenosine kinase inhibitor 5 iodotubercidin, whereas they were not affected by ibuprofen or 8 phenyltheophylline, and were not reproduced by non-metabolized adenosine analogues. In comparison with adenosine, ATP caused a slower decrease of Pi and of glycogenolysis. The fate of the cytosolic Pi was unclear, especially with administered ATP, which did not increase the n.m.r.-detectable intracellular ATP. PMID- 1872796 TI - ADP-ribosylation of core histones and their acetylated subspecies. AB - ADP-ribosylation of core histones was investigated in isolated nuclei of Physarum polycephalum. Core histone species differed in the mode of modification. Whereas ADP-ribosylation of H2A and H2B is sensitive to inhibition by 3-methoxybenzamide, as with most other nuclear acceptor proteins, the modification of H3 and H4 is not inhibited. Cleavage experiments with hydroxylamine indicate a carboxylate ester type ADP-ribose-protein bond for H2A and H2B and arginine-linked ADP-ribose residues for H3 and H4. ADP-ribosylation preferentially occurs on acetylated histone subspecies, as shown for H4. These data are substantiated by the use of n butyrate, which induces hyperacetylation of core histones; the butyrate-induced shift towards more acetylated H4 subspecies is accompanied by an increase of ADP ribose incorporation into highly acetylated H4 subspecies. PMID- 1872797 TI - A study of properties and abundance of the components of liver carnitine palmitoyltransferases in mitochondrial inner and outer membranes. Effects of hypothyroidism, fasting and a ketotic diabetic state. AB - 1. Liver mitochondrial outer and inner membranes were isolated from normal, 48 h fasted, streptozotocin-diabetic and hypothyroid rats. 2. Relative to membrane protein, fasting and diabetes substantially increased the activity of carnitine palmitoyltransferase (CPT) in outer membranes. Inner-membrane CPT specific activity was only slightly altered, being increased in diabetes and decreased in hypothyroidism. Abundance of an inner-membrane Mr-68,000 polypeptide that cross reacted with an anti-CPT serum was significantly increased in diabetes and hypothyroidism. Relative to inner-membrane CPT activity, this cross-reactivity was increased by 37% in diabetes and by 400% in hypothyroidism, suggesting modification of the intrinsic activity of the CPT in these states. 3. CPT in outer membranes was inhibitable by malonyl-CoA, whereas inner-membrane CPT was insensitive to malonyl-CoA. Fasting and diabetes increased the IC50 (concentration of malonyl-CoA causing 50% inhibition) for outer-membrane CPT, whereas the IC50 was decreased in hypothyroidism. 4. Binding of [14C]malonyl-CoA was observed with both outer and inner membranes and was fitted to two-site models in each case. Fasting, diabetes and hypothyroidism changed the KD for binding at the higher-affinity site in outer membranes in a manner that correlated closely with changes in IC50 for inhibition of outer-membrane CPT by malonyl-CoA. Fasting and diabetes increased the abundance of this outer-membrane high-affinity malonyl-CoA-binding site, whereas hypothyroidism decreased its abundance. PMID- 1872798 TI - Tartrate-resistant acid phosphatase from human osteoclastomas is translated as a single polypeptide. AB - Tartrate-resistant acid phosphatases have been isolated from a number of sources. These enzymes consist of one subunit (Mr 30,000-40,000) or two dissimilar subunits (Mr 15,000-20,000). Previously we isolated the enzyme from human osteoclastomas, as a two-subunit protein. By Northern blotting and hybridization with radiolabelled oligonucleotides corresponding to the N-terminal sequences of the two subunits, we demonstrate here that the enzyme is transcribed as one mRNA which is translated in vitro to produce a single polypeptide of approx. Mr 33,000. Transcription as a single mRNA species is also the case in other tissues. These results suggest that the osteoclastoma enzyme undergoes post-translational modification in the form of cleavage of a single peptide bond to give a disulphide-bonded two-subunit protein. PMID- 1872800 TI - Effect of magnesium ions on the inhibition of S-adenosylmethionine decarboxylase from Escherichia coli by [2-(amino-oxy)ethyl](5'-deoxyadenosin-5' yl)(methyl)sulphonium . AB - [2-(Amino-oxy)ethyl](5'-deoxyadenosin-5'-yl)(methyl)sulphonium+ ++, the amino-oxy analogue of decarboxylated S-adenosylmethionine, is a potent irreversible inhibitor of Escherichia coli S-adenosylmethionine decarboxylase [Khomutov, Zavalova, Syrku, Artamonova & Khomutov (1983) Bioorg. Khim. 9, 130-131; Artamonova, Zavalova, Khomutov & Khomutov (1986) Bioorg. Khim. 12, 206-212]. We have shown that Mg2+ ions are required for the irreversible inhibition of the decarboxylase, and that S-adenosylmethionine protects against this inhibition. PMID- 1872799 TI - Phosphorylation of the small heat-shock protein is regulated by interleukin 1, tumour necrosis factor, growth factors, bradykinin and ATP. AB - Interleukin 1 (IL1) increased phosphorylation of the small heat-shock protein (hsp 27) in MRC5 fibroblasts. The increase was maintained for at least 30 min, but levels had returned to pre-stimulation values by 2 h. When hsp 27 was metabolically labelled with [3H]leucine, about 15% was phosphorylated in resting confluent cells; this rose to 90% upon stimulation by IL1. Peptide maps of the three differently charged phosphorylated forms were consistent with their arising by phosphorylation of increasing numbers of serine residues. IL1 had the same effect on hsp 27 in pig articular chondrocytes, endothelial cells from human umbilical vein and an epidermoid carcinoma cell line (KB). Certain other agents were found selectively to increase phosphorylation of hsp 27 in MRC5 cells besides IL1 [and tumour necrosis factor (TNF)]. Platelet-derived growth factor had a similar effect to that of IL1; bradykinin, acid fibroblast growth factor and ATP caused an intermediate effect; phorbol myristate acetate (PMA) and 1 oleoyl-2-acetylglycerol had smaller effects. Dibutyryl cyclic AMP and forskolin had no effects on hsp 27 phosphorylation. When cells had been depleted of protein kinase C (PKC) by prolonged treatment with PMA, stimulation by IL1, TNF or bradykinin still increased hsp 27 phosphorylation. The stimulation by all three agents was also unaffected by the PKC inhibitor staurosporine. IL1, TNF and bradykinin each caused hsp 27 phosphorylation by a pathway independent of PKC. The results are consistent with IL1 activating a serine kinase which remains to be identified. PMID- 1872801 TI - Structural and functional studies on the human hepatic interleukin-6 receptor. Molecular cloning and overexpression in HepG2 cells. AB - cDNAs coding for the human hepatic interleukin-6 receptor (IL-6-R) have been isolated from a library made from poly(A) RNA of dexamethasone-treated human hepatoma cells (HepG2). We found the hepatic IL-6-R to be identical to the one expressed by leucocytes. A polyclonal antiserum was raised in rabbits against the IL-6-R protein expressed in Escherichia coli. Although the entire IL-6-R protein was used for immunization, only antibodies to the cytoplasmic domain of the IL-6 R were obtained. It is demonstrated by affinity cross-linking and subsequent immunoprecipitation with antibodies against the ligand as well as against the receptor that the cloned cDNA codes for the functional IL-6-R on HepG2 cells. When the hepatic IL-6-R cDNA was overexpressed in HepG2 cells, these cells became more sensitive to low concentrations of IL-6 with respect to the induction of gamma-fibrinogen mRNA. PMID- 1872802 TI - Identification of residues in ornithine decarboxylase essential for enzymic activity and for rapid protein turnover. AB - The importance of certain amino acid residues in mammalian ornithine decarboxylase activity and degradation was studied by site-specific mutagenesis. Changes were made to the mouse ornithine decarboxylase cDNA in a plasmid containing a T7 RNA polymerase promoter. The plasmid was then used for the synthesis of RNA, which was translated in a reticulocyte lysate system. The activity of the ornithine decarboxylase formed and the stability of the protein to degradation in a reticulocyte lysate system were determined. Changes of lysine 169 or of histidine-197 to alanine completely abolished enzyme activity, indicating that these residues are essential for enzyme activity. The removal of the C-terminal 36 residues, the mutation of lysine-349 to alanine, of lysine-298 to alanine or the double change of serine-303 and glutamic acid-308 to alanine residues still resulted in an active enzyme. The last-mentioned finding indicates that the phosphorylation of serine-303 does not play an essential role in the catalytic activity of ornithine decarboxylase. The control ornithine decarboxylase protein was degraded rapidly in a reticulocyte lysate provided that ATP was added. The truncated protein missing the 36 residues from the C-terminus was much more stable in this system, and the protein containing the double change of serine-303 and glutamic acid-308 to alanine residues was slightly more stable than control ornithine decarboxylase protein. These results indicate that the altered residues may play a role in interaction with factors responsible for the rapid turnover of ornithine decarboxylase. PMID- 1872803 TI - Deletion of two growth-factor repeats from the low-density-lipoprotein receptor accelerates its degradation. AB - The region of the low-density-lipoprotein (LDL) receptor showing sequence similarity to the epidermal-growth-factor (EGF) precursor is required for LDL binding and the acid-induced dissociation of ligand and receptor. We describe here a naturally occurring mutant LDL receptor, found in a patient with homozygous familial hypercholesterolaemia, which lacks the first two growth factor-like repeats of the EGF-precursor-like ('homology') domain. The mutation in the receptor gene is a 2.5 kb deletion including exons 7 and 8. The molecular mass of the mutant receptor (145 kDa) was approx. 15 kDa smaller than the normal LDL receptor. The mutant receptors were derived from precursors (105 kDa) that apparently underwent normal processing. Fibroblasts from the patient had high affinity binding sites for the the apolipoprotein E-containing ligand, beta VLDL, but did not bind LDL. In the presence of beta VLDL, receptors were rapidly degraded. The mutant receptors also displayed an abnormally rapid turnover, about four times faster than that of normal receptors, in the absence of ligand; this accelerated degradation accounted for the low level of expression of mutant receptors in up-regulated cells. These data support a role for the growth-factor like repeats in the binding of LDL (but not beta VLDL) and in receptor recycling, and indicate that a normal rate of turnover of unoccupied receptors is dependent on the integrity of these segments of the protein. PMID- 1872804 TI - cis-recognition and degradation of ornithine decarboxylase subunits in reticulocyte lysate. AB - One of the most interesting characteristics of ornithine decarboxylase (ODC) is its extremely short half-life. In a recent study we have demonstrated that deletion of a C-terminal segment converts ODC into a stable protein. In the present study we have extended this observation by testing the degradation of an ODC heterodimer composed of one rapidly degraded wild-type subunit and one stable mutant subunit. Our study was motivated by the possibility of trans-recognition of stable subunits due to their association with labile subunits. Our results demonstrate that such an association did not confer lability upon the stable subunits, not did it stabilize the short-lived subunits. PMID- 1872805 TI - Hyperammonaemia depresses glucose consumption throughout the brain. AB - Recent studies showed that hyperammonaemia caused many of the metabolic changes in portacaval-shunted rats, a model of hepatic encephalopathy. These changes included a depression in the cerebral metabolic rate of glucose (CMRGlc), an indication of decreased brain function. 2. The purpose of the present experiments was to determine whether the depression of CMRGlc caused by ammonia is confined to certain brain structures, or whether the depression is an overall decrease in all structures, such as occurs in portacaval-shunted rats. To accomplish this objective, rats were made hyperammonaemic by giving them intraperitoneal injections of 40 units of urease/kg body wt. every 12 h; control rats received 0.154 m-NaCl. CMRGlc was measured 48 h after the first injection, by using quantitative autoradiography with [6-14C]glucose as a tracer. 3. The experimental rats had high plasma ammonia concentrations (control 70 nmol/ml, experimental 610 nmol/ml) and brain glutamine levels (control 5.4 mumol/ml). Hyperammonaemia decreased CMRGlc throughout the brain by an average of 19%. CMRGlc showed an inverse correlation with plasma ammonia, but a stronger correlation with the brain glutamine content. 4. Hyperammonaemia led to a decrease in CMRGlc throughout the brain that was indistinguishable from the pattern seen in portacaval-shunted rats. This is taken as further evidence that the cerebral depression found in portacaval-shunted rats is a consequence of hyperammonaemia. The observation that depression of CMRGlc correlated more closely with brain glutamine content than with plasma ammonia suggests that metabolism of ammonia is an important step in the pathological sequence. PMID- 1872807 TI - Differential expression of the mouse U1a and U1b SnRNA genes is not dependent on sequence differences in the octamer motif. AB - The mouse U1b SnRNA gene is expressed in only a limited range of cell types, whereas the U1a SnRNA gene is expressed in all cells. These two genes differ in the sequence of the octamer motif, which plays a critical role in SnRNA gene regulation. We show that the U1b octamer binds the octamer-binding protein Oct-1 with higher affinity than does the U1a octamer in both U1b-expressing and -non expressing cell lines and tissues. Moreover, the U1b octamer can direct a higher level of gene expression than the U1a octamer when linked to a heterologous promoter and introduced into a non-U1b-expressing cell line. Hence the tissue specific expression of the U1b gene is not determined by the failure of its octamer motif to bind Oct-1 or the weak affinity of this binding. PMID- 1872806 TI - Hyperammonaemia does not impair brain function in the absence of net glutamine synthesis. AB - 1. It has been established that chronic hyperammonaemia, whether caused by portacaval shunting or other means, leads to a variety of metabolic changes, including a depression in the cerebral metabolic rate of glucose (CMRGlc) increased permeability of the blood-brain barrier to neutral amino acids, and an increase in the brain content of aromatic amino acids. The preceding paper [Jessy, DeJoseph & Hawkins (1991) Biochem. J. 277, 693-696] showed that the depression in CMRGlc caused by hyperammonaemia correlated more closely with glutamine, a metabolite of ammonia, than with ammonia itself. This suggested that ammonia (NH3 and NH4+) was without effect. The present experiments address the question whether ammonia, in the absence of net glutamine synthesis, induces any of the metabolic symptoms of cerebral dysfunction associated with hyperammonaemia. 2. Small doses of methionine sulphoximine, an inhibitor of glutamine synthetase, were used to raise the plasma ammonia levels of normal rats without increasing the brain glutamine content. These hyperammonaemic rats, with plasma and brain ammonia levels equivalent to those known to depress brain function, behaved normally over 48 h. There was no depression of cerebral energy metabolism (i.e. the rate of glucose consumption). Contents of key intermediary metabolites and high-energy phosphates were normal. Neutral amino acid transport (tryptophan and leucine) and the brain contents of aromatic amino acids were unchanged. 3. The data suggest that ammonia is without effect at concentrations less than 1 mumol/ml if it is not converted into glutamine. The deleterious effect of chronic hyperammonaemia seems to begin with the synthesis of glutamine. PMID- 1872808 TI - Biosynthesis and secretion of triacylglycerol in rat liver after partial hepatectomy. AB - Partially hepatectomized rats were used to investigate the mechanism of fatty liver development in the regenerating rat liver. After partial hepatectomy the amount of hepatic triacylglycerol increased by almost 4-fold compared with sham operated rats. The activities of both cytosolic and microsomal phosphatidate phosphohydrolase were enhanced at 12 h after surgery. The activity of diacylglycerol acyltransferase was increased at a later stage of regeneration. Analysis of plasma lipoproteins showed a significant decrease of lipids associated with very-low-density lipoproteins (VLDL). Relative to control, the rate of hepatic triacylglycerol synthesis from [3H]glycerol in vivo was stimulated at 22 h after partial liver resection. However, secretion of glycerol labelled triacylglycerol in VLDL was the same in control and hepatectomized rats. In cultures of hepatocytes from hepatectomized donor rats, the concentration of triacylglycerol and the biosynthesis of this lipid from [3H]glycerol or from [3H]oleate were enhanced. The secretion of total triacylglycerol into the medium was not affected, resulting in a net accumulation of intracellular triacylglycerol. The rate of secretion of leucine-labelled apolipoproteins B and E associated with VLDL was similar in cell cultures from hepatectomized and sham operated rats. The results of this study show that the enhancement of the biosynthesis of triacylglycerol in hepatectomized livers is not accompanied by an increase of the secretion of VLDL. PMID- 1872809 TI - Angiotensin receptors from rat liver, brain and pituitary gland. Expression of two subtypes in Xenopus oocytes. AB - Xenopus laevis oocytes were used to express angiotensin receptors encoded by mRNAs extracted from rat liver, adenohypophysis and brain. Groups of ten mRNA injected oocytes were loaded with 45Ca2+ and the responsiveness to angiotensin II (A II) and related molecules tested by monitoring 45Ca2+ outflux. A II and angiotensin III (A III) induced a marked and transient increase in 45Ca2+ outflux from mRNA, but not from control, water-injected, oocytes. The increase over basal value of 45Ca2+ outflux during a 5 min application period of A II or A III was used as a response index. Observed responses were of high magnitude, reproducible and dose-dependent. For these reasons, mRNA-injected oocytes constitute a valuable system for investigating the pharmacological properties of angiotensin receptors from tissues of different origin under experimental conditions which eliminate tissue-specific interference which might be encountered in classical binding studies on acellular preparations. We demonstrate a fairly good parallelism between the relative potencies of A I, A II and A III in eliciting an increase in 45Ca2+ outflux from liver and adenohypophyseal mRNA-injected oocytes and the relative affinities of these peptides for binding to liver or adenohypophyseal membranes (A II greater than A III much greater than A I). The predominant receptor subtype expressed by brain mRNA discriminated very poorly between A II and A III, whereas angiotensin receptors expressed by liver or adenohypophyseal mRNA discriminated between AII and AIII very efficiently. PMID- 1872810 TI - Nitrogenase of Klebsiella pneumoniae. Reversibility of the reductant-independent MgATP-cleavage reaction is shown by MgADP-catalysed phosphate/water oxygen exchange. AB - The steady-state kinetics of reductant-independent ATP hydrolysis by Klebsiella pneumoniae nitrogenase at 23 degrees C at pH 7.4 were determined as a function of component protein ratio (optimal at an oxidized Fe protein/MoFe protein ratio of 3:1) and MgATP concentration (Km 400 microM). Competitive inhibition was observed for MgADP (Ki 145 microM), [beta gamma-methylene]ATP (Mgp[CH2]ppA) (Ki 115 microM), [beta gamma-monofluoromethylene]ATP (Mgp[CHF]ppA) (Ki 53 microM) and [beta gamma-difluoromethylene]ATP (Mgp[CF2]ppA) (Ki 160 microM). The tighter binding of MgADP to free oxidized Fe protein (KD less than 10 microM) than to the oxidized Fe protein-MoFe protein complex (Ki 145 microM) is proposed as the driving force that induces rate-limiting protein dissociation in the catalytic cycle of nitrogenase. The reversible nature of the reductant-independent MgATP cleavage reaction was demonstrated by an MgADP-induced enhancement of the rate of the phosphate/water oxygen exchange reaction with 18O-labelled phosphate ion. This enhancement, like the reductant-independent ATPase reaction, only occurred with the complex formed by oxidized Fe protein and MoFe protein and not with the individual proteins. The results are discussed in terms of the mechanism of ATP hydrolysis by nitrogenase and other systems involving protein-protein interactions. PMID- 1872811 TI - The substrate-specificity of human lysosomal alpha-D-mannosidase in relation to genetic alpha-mannosidosis. AB - The specificity of human liver lysosomal alpha-mannosidase (EC 3.2.1.24) towards a series of oligosaccharide substrates derived from high-mannose, complex and hybrid asparagine-linked glycans and from the storage products in alpha mannosidosis was investigated. The enzyme hydrolyses all alpha(1-2)-, alpha(1-3)- and alpha(1-6)-mannosidic linkages in these glycans without a requirement for added Zn2+, albeit at different rates. A major finding of this study is that all the substrates are hydrolysed by non-random pathways. These pathways were established by determining the structures of intermediates in the digestion mixtures by a combination of h.p.t.l.c. and h.p.l.c. before and after acetolysis. The catabolic pathway for a particular substrate appears to be determined by its structure, raising the possibility that degradation occurs by an uninterrupted sequence of steps within one active site. The structures of the digestion intermediates are compared with the published structures of the storage products in mannosidosis and of intact asparagine-linked glycans. Most but not all of the digestion intermediates derived from high-mannose glycans have structures found in intact asparagine-linked glycans of human glycoproteins or among the storage products in the urine of patients with mannosidosis. However, the relative abundances of these structures suggests that the catabolic pathway is not the same as the processing pathway. In contrast, the intermediates formed from the digestion of oligosaccharides derived from hybrid and complex N-glycans are completely different from any processing intermediates and also from the oligosaccharides of composition Man2-4GlcNAc that account for 80-90% of the storage products in alpha-mannosidosis. It is postulated that the structures of these major storage products arise from the action of an exo/endo-alpha(1-6) mannosidase on the partially catabolized oligomannosides that accumulate in the absence of the main lysosomal alpha-mannosidase. PMID- 1872812 TI - The effect of the carbohydrate moiety upon the size and conformation of human plasma galactoglycoprotein as judged by electron microscopy and circular dichroism. Structural studies of a glycoprotein after stepwise enzymic carbohydrate removal. AB - Galactoglycoprotein is a unique human plasma protein [76% carbohydrate (23% N acetylneuraminic acid, 20% galactose, 3% mannose, 1% fucose and 29% N acetylgalactosamine plus N-acetylglucosamine) and 24% polypeptide, a single polypeptide chain of about 200 amino acid residues that is high in serine and threonine content] [Schmid, Mao, Kimura, Hayashi & Binette (1980) J. Biol. Chem. 255, 3221-3226]. Highly purified exoglycosidases with well-defined specificities were used to prepare five derivatives of galactoglycoprotein in which sequential residues of N-acetylneuraminic acid, galactose, N-acetylglucosamine, a second galactose and N-acetylgalactosamine were removed with 83% of the total carbohydrate cleaved. C.d. shows that native galactoglycoprotein and all derivatives in aqueous buffer are predominantly random coil, suggesting that removal of a large number of electrostatic net charges, as well as the major portion of the carbohydrate moiety, does not alter the secondary structure of the polypeptide chain. Examination of the size and conformation of tungsten-shadowed galactoglycoprotein and asialo and agalacto derivatives by electron microscopy shows the size and conformation of all three preparations to be similar, with only minor differences in particle length and width. PMID- 1872813 TI - Purification of a protease in red blood cells that degrades oxidatively damaged haemoglobin. AB - Haemoglobin damaged by exposure of red blood cells to oxidants is rapidly degraded by a proteolytic pathway which does not require ATP [Fagan, Waxman & Goldberg (1986) J. Biol. Chem. 261, 5705-5713]. By fractionating erythrocyte lysates, we have purified two proteases which hydrolyse oxidatively damaged haemoglobin (Ox-Hb). One protease hydrolysed small fluorogenic substrates in addition to Ox-Hb. Its molecular mass was approximately 700 kDa and it consisted of several subunits ranging in size from 22 to 30 kDa. This enzyme may be related to the high-molecular-mass multicatalytic proteinase previously isolated from a variety of tissue and cell types. The other Ox-Hb-degrading activity had an apparent molecular mass of 400 kDa on gel filtration, a subunit size of 110 kDa and an isoelectric point between 4.5 and 5.0. This protease also hydrolysed the small polypeptides insulin and glucagon, as well as other large proteins such as lysozyme. Insulin blocked the degradation of Ox-Hb and Ox-Hb blocked the hydrolysis of insulin by the purified protease. Thiol reagents and metal chelators strongly inhibited the hydrolysis of both Ox-Hb and insulin, whereas inhibitors of serine, aspartic and thiol proteases had little effect. These properties suggest that the Ox-Hb-degrading activity purified from rabbit erythrocytes is the cytosolic insulin-degrading enzyme that is believed to play a role in the metabolism of insulin in several tissues. We propose that this enzyme may also function as a key component in a cytoplasmic degradative pathway responsible for removing proteins damaged by oxidants. PMID- 1872814 TI - Heterogeneity of rat liver cytosol casein kinase 2. Association between the alpha/alpha' -subunits of casein kinase 2 and the phosphorylatable protein pp49. AB - Casein kinase 2 activity could be resolved into three peaks by chromatography on DEAE-Sepharose. The peak eluted at high salt concentrations (casein kinase 2b) showed molecular and kinetic properties typical of the heterotetramer composed of alpha-(or alpha'-) and beta-subunits. In contrast, the peak that was eluted at low salt concentrations (casein kinase 2a) contained no beta-subunit but a phosphorylatable protein of 49 kDa (pp49), in addition to the alpha/alpha' subunits. The presence of alpha/alpha'/alpha"-subunits in preparations of casein kinases 2a and 2b was confirmed by immunological assays. Casein kinase 2a had low specific activity and a very high apparent Km for beta-casein. The peak eluted at intermediate ionic strength contained the alpha/alpha'-subunits and variable amounts of beta-subunit and pp49, and had kinetic properties intermediate between those of casein kinases 2a and 2b. Experiments based on heat inactivation, inhibition by low concentrations of heparin and ability to use GTP as substrate suggested that phosphorylation of pp49 was catalysed by the alpha/alpha'-subunits of casein kinase 2. No similarities were observed in the phosphopeptide maps of pp49 and beta-subunit. These results show that the alpha/alpha'-subunits of rat liver cytosol casein kinase 2 can form complexes not only with the beta-subunit but also with pp49, and that the complexes containing pp49 have a reduced affinity for the exogenous protein substrate beta-casein. PMID- 1872815 TI - Subcellular fractionation to junctional sarcoplasmic reticulum and biochemical characterization of 170 kDa Ca(2+)- and low-density-lipoprotein-binding protein in rabbit skeletal muscle. AB - Skeletal-muscle sarcoplasmic reticulum (SR) comprises two distinct domains, corresponding to the free membrane of longitudinal SR (LSR) and the junctional membrane region of the terminal cisternae (TC), respectively. The junctional membrane contains the ryanodine receptor (RyR)/Ca(2+)-release channel and additional minor protein components that still require biochemical investigation, in relation to excitation-contraction coupling. Recent findings suggested the involvement in this process of a 170 kDa protein [Kim, Caswell, Talvenheimo & Brandt (1990) Biochemistry 29, 9281-9289], also characterized as a phosphoprotein in junctional TC in independent studies [Chu, Submilla, Inesi, Jay & Campbell (1990) Biochemistry 29, 5899-5905]. We show that this protein is a specific substrate of exogenous cyclic AMP-dependent protein kinase, that it is exposed to the outer surface of intact TC vesicles, and that it co-localizes with the RyR to the junctional membrane. Comparative analysis of LSR and TC subfractions for the 160 kDa glycoprotein sarcalumenin, using Western-blot techniques and specific monoclonal antibodies or concanavalin A as a ligand, revealed that the distribution of this protein within the SR corresponds inversely to both that of the RyR and of the 170 kDa protein. The 170 kDa protein, like sarcalumenin, stains blue with the cationic dye Stains-All and binds 45Ca2+ on blots, but it is uniquely distinguished by its ability to bind 125I-labelled low-density lipoprotein. The similarity of these properties, as well as the pI and solubility properties, to those described for the SR protein, recently purified and cloned and named histidine-rich Ca(2+)-binding protein [HCP; Hofmann, Brown, Lee, Pathak, Anderson & Goldstein (1989) J. Biol. Chem. 264, 8260-8270], makes it very likely that our protein and HCP may indeed be identical. The protein described in the present study differs from sarcalumenin because its migration in SDS/PAGE is accelerated in the presence of Ca2+, a previously reported property of other Ca(2+)-binding proteins [leMaire, Lund, Viel, Champeil & Moller (1989) J. Biol. Chem. 265, 1111-1123], arguing for Ca(2+)-induced protein-conformational changes. Kinase-dependent phosphorylation of our protein is another distinguishing feature, which, although not previously reported for HCP, is consistent with the presence of potential serine/threonine phosphorylation sites in the middle portion of the cloned HCP molecule. The finding that HCP, contrary to early views, selectively binds to the cytoplasmic side of the junctional membrane, together with its newly characterized properties, seem to provide new clues as to a possible role in electromechanical coupling and/or Ca2+ release. PMID- 1872816 TI - Stimulation of cell proliferation in skeletal tissues of the rat by defined parathyroid hormone fragments. AB - We have found, in previous studies in vitro using skeletal derived cell cultures, that mid-region fragments of human parathyroid hormone (hPTH) stimulate [3H]thymidine incorporation into DNA and increase the specific activity of the brain-type isoenzyme of creatine kinase (CK). These changes occurred without an increase in cyclic AMP formation which is linked to bone resorption. In this study, we found that the mid-region fragment hPTH-(28-48) stimulated CK activity in diaphysis, epiphysis and kidney in a time- and dose-dependent manner, parallel to the effects of the whole molecule bovine (b)PTH-(1-84) and the fully active fragment hPTH-(1-34). The increase caused by hPTH-(28-48) at a dose of 1.25 micrograms/rat was not less than the 2-fold increase caused by a roughly equimolar concentration bPTH-(1-84). A significant increase was reached at 1 h after intraperitoneal injection in all cases. All three sequences of PTH caused an increase in [3H]thymidine incorporation into DNA in diaphysis and epiphysis, but not in kidney, 24 h after injection. A fragment further towards the C terminal, hPTH-(34-47), was inactive compared with an equimolar concentration of the fragment hPTH-(25-39), which stimulated both CK activity and DNA synthesis. These results in vivo are in line with previous findings in vitro; they provide further support for the suggestion that mid-region fragments of the PTH molecule could be used to induce bone formation without incurring the deleterious effect of bone resorption. PMID- 1872817 TI - Identification of inducible damage-recognition proteins that are overexpressed in HeLa cells resistant to cis-diamminedichloroplatinum (II). AB - Two cis-diamminedichloroplatinum (II) (cisplatin)-inducible proteins [b 130 (approximately 130 kDa) and b95 (approximately 95 kDa]) in HeLa cells that recognize both the cisplatin-modified and u.v.-modified DNA were identified in this study. These damage-recognition proteins were overexpressed in cisplatin resistant HeLa cells. The results suggest that the damage-recognition proteins are regulated in the cells in response to DNA damage, and they may be important for DNA repair and probably the emergence of cisplatin resistance. PMID- 1872818 TI - Electroporation can cause artefacts due to solubilization of cations from the electrode plates. Aluminum ions enhance conversion of inositol 1,3,4,5 tetrakisphosphate into inositol 1,4,5-trisphosphate in electroporated L1210 cells. AB - 1. In electroporated L1210 cells, Ins(1,3,4,5)P4 causes Ca2+ release, owing to its conversion into Ins(1,4,5)P3, but this does not happen in cells permeabilized by digitonin treatment [Cullen, Irvine, Drobak & Dawson (1989) Biochem. J. 259, 931-933]. 2. If the assay medium is subjected to electroporation by using a commercially available electroporation apparatus and then the cells are added and permeabilized with digitonin, the cells behave as if they had been electroporated. 3. Electroporation causes the release of high concentrations of Al3+ into the experimental medium, and addition of these concentrations of Al3+ into the experimental medium mimics the effect of electroporation on the conversion of Ins(1,3,4,5)P4 into Ins(1,4,5)P3. 4. It is concluded that the difference between electroporated and digitonin-permeabilized L1210 cells in this experimental system can be attributed to dissolution of Al3+ from the electroporation cuvette. Al3+ contamination may thus be a serious problem when using this apparatus. PMID- 1872819 TI - Thermostable cellobiohydrolase from the thermophilic eubacterium Thermotoga sp. strain FjSS3-B.1. Purification and properties. AB - Exo-1,4-beta-cellobiohydrolase (EC 3.2.1.91) was isolated from the culture supernatant of Thermotoga sp. strain FjSS3-B.1, an extremely thermophilic eubacterium that grows optimally at 80 degrees C. The enzyme was purified to homogeneity as determined by SDS/PAGE and has an Mr of 36,000. The enzyme is the most thermostable cellulase reported to date, with a half-life at 108 degrees C of 70 min in buffer. In a 40 min assay, maximal activity was recorded at 105 degrees C. Cellobiohydrolase from strain FjSS3-B.1 is active against amorphous cellulose and CM-cellulose but only effects limited hydrolysis of filter paper or Sigmacell 20. The only product identified by h.p.l.c. is the disaccharide cellobiose. The enzyme has a pH optimum around neutral and is stabilized by the presence of 0.8 M-NaCl. PMID- 1872820 TI - A heat-inducible nuclear factor that binds to the heat-shock element of the human haem oxygenase gene. AB - Haem oxygenase is a heat-shock protein in several rat tissues, as well as in certain human cells such as Hep3B hepatoma cells. In common with other heat-shock protein genes, both the human and the rat haem oxygenase genes contain a heat shock element (HSE) in their promoter regions. In the present study we have identified a factor in nuclear extracts of human Hep3B cells which binds specifically to the HSE of the human haem oxygenase gene. The factor in Hep3B cells was significantly induced within 1 h after heat-shock treatment, and the induction was blocked by treatment of cells with actinomycin D or cycloheximide. The factor was not detected in human HepG2 hepatoma cells, which exhibit the heat mediated induction of heat-shock protein 70 mRNA, but not that of haem oxygenase mRNA. These findings suggest that the heat-inducible nuclear factor is increased at the level of transcription and that it may activate the human haem oxygenase gene via the HSE after heat treatment. PMID- 1872821 TI - High frequency force generation in outer hair cells from the mammalian ear. AB - Mammalian outer hair cells generate mechanical forces at acoustic frequencies and can thus amplify the sound stimulus within the inner ear. The mechanism of force generation depends upon the plasma membrane potential but not upon either calcium or ATP. Forces are generated in the lateral cortex along the full length of the cell. The cortex includes a two-dimensional cytoskeletal lattice composed of circumferential filaments 6-7 nm thick that are cross-linked by filaments 3-4 nm thick and 40-60 nm long. The two filament types may, respectively, be actin and some form of spectrin. The lattice reinforces the cylindrical shape of the cell and permits limited changes in length. Beneath it lie the lateral cisternae, a regular system of multi-layered membranes. Force-generation may depend upon voltage-dependent shape changes in proteins that lie either in the plasma membrane or in the cytoskeletal lattice. PMID- 1872823 TI - Stem cells and the elixir of life. PMID- 1872822 TI - A role for interferons in early pregnancy. AB - In order to survive, the developing conceptus must interrupt the normal ovarian cycle of the mother and extend the production of progesterone by the corpus luteum. An unusual Type 1 interferon (IFN), related structurally to the IFN-alpha molecule and produced in massive amounts for only a few days by the first epithelium (trophectoderm) of the preimplantation conceptus, has been implicated as the antiluteolytic agent in sheep and cattle. IFN-alpha therapy during this critical period can also improve pregnancy success in sheep. It remains unclear, however, whether the trophoblast IFN have specialized biological properties or whether they are unique merely in the timing, magnitude and site of their expression. PMID- 1872824 TI - Identifying genes within the genome: new ways for finding the needle in a haystack. PMID- 1872825 TI - A common structural motif in nuclear pore proteins (nucleoporins) PMID- 1872826 TI - Effect of synthesized constituents in the L-tryptophan product on the differentiation of eosinophils and the induction of IL-6: a possible cause of eosinophilia-myalgia syndrome. AB - While the pathogenesis of eosinophilia-myalgia syndrome (EMS) remains obscure, the ingestion of L-trypophan (LT) and possibly certain constituents in the LT product might be associated. We investigated the effect of chemically synthesized substances, 1,1'-ethylidene bis[tryptophan] (EBT) and its decomposition product, 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) recently identified in the implicated LT, on the eosinophil differentiation and the induction of IL-1 and IL-6. EBT and MTCA alone did not support colony formation. However, EBT or MTCA in conjunction with IL-2 induced colony-forming activity containing a small number of eosinophils. In addition, these LT constituents induced a significant level of IL-6 but not IL-1 beta in the mononuclear cells from normal volunteers and a patient with hypereosinophilic syndrome. These results suggest that certain constituents of LT product are associated with the pathogenesis of EMS through the induction of colony-stimulating factors and IL-6, hence giving rise to eosinophilia and inflammation. PMID- 1872827 TI - Differential genomic susceptibility in malignancy correlates with changes in ATATAT DNA-binding proteins. AB - Accesibility to DNA in the nucleus is important for the regulation of gene expression and for the effect of DNA-modifying drugs. We have now studied differential genome susceptibility in normal melanocytes and the corresponding malignant melanoma. DNA hypersensitivity assays revealed a markedly lesser degradation in melanoma nuclei compared to that in melanocytes. Cross-linking of DNA to nuclear proteins by ultraviolet light showed a cell-type dependent inverse correlation of genomic susceptibility with binding of (dA.dT) (dA.dT) sequences, compared to that shown with (dG.dC) (dG.dC), regardless of methylation in cytosines. Exposure to cholera toxin partly reversed genomic susceptibility and increased DNA/protein cross-linking in melanocytes. In contrast, melanoma cells showed decreased DNA/protein interactions and greater genome susceptibility after exposure to cholera toxin or okadaic acid. Our data suggest that a molecular mechanism for differential genome exposure in cancer cells involves a modified expression of sequence-specific DNA-binding proteins. PMID- 1872828 TI - Degradation of azo compounds by ligninase from Phanerochaete chrysosporium: involvement of veratryl alcohol. AB - Phanerochaete chrysosporium decolorized several polyaromatic azo dyes in ligninolytic culture. The oxidation rates of individual dyes depended on their structures. Veratryl alcohol stimulated azo dye oxidation by pure lignin peroxidase (ligninase, LiP) in vitro. Accumulation of compound II of lignin peroxidase, an oxidized form of the enzyme, was observed after short incubations with these azo substrates. When veratryl alcohol was also present, only the native form of lignin peroxidase was observed. Azo dyes acted as inhibitors of veratryl alcohol oxidation. After an azo dye had been degraded, the oxidation rates of veratryl alcohol recovered, confirming that these two compounds competed for ligninase during the catalytic cycle. Veratryl alcohol acts as a third substrate (with H2O2 and the azo dye) in the lignin peroxidase cycle during oxidations of azo dyes. PMID- 1872829 TI - Different substrate specificities of lanosterol 14a-demethylase (P-45014DM) of Saccharomyces cerevisiae and rat liver for 24-methylene-24,25-dihydrolanosterol and 24,25-dihydrolanosterol. AB - The purified lanosterol 14a-demethylase (P-45014DM) of S. cerevisiae catalyzed the 14a-demethylation of 24-methylene-24,25-dihydrolanosterol (24-methylenelanost 8-en-3 beta-ol, 24-methylene-DHL), the natural substrate of the demethylase of filamentous fungi, as well as its natural substrate, lanosterol. Lanosterol 14a demethylase of rat liver microsomes also catalyzed the 14a-demethylation of 24 methylene-DHL, but the activity was considerably lower than that for lanosterol. The activity of the rat liver enzyme for 24-methylene-DHL was also lower than that for 24,25-dihydrolanosterol (DHL), while the activity of yeast P-45014DM for 24-methylene-DHL was considerably higher than that for DHL. Since 24-substituted sterols are not found in mammals and DHL is not an intermediate of ergosterol biosynthesis by yeast, above-mentioned different substrate specificities between the yeast and the mammalian 14a-demethylases may reflect certain evolutional alteration in their active sites in relation to the difference in their sterol biosynthetic pathways. PMID- 1872830 TI - Partial structure of the human H-protein gene. AB - In a span of approximately 13 kb, two genomic fragments showing an obvious overlap encoded the 1,192 base pair (bp) cDNA sequence for human H-protein. Because of the close similarity in the genomic organization comprised of five exons to that for the chicken H-protein gene, this region was assigned to the true H-protein gene in human. Primer extension analysis suggested and S1 protection analysis confirmed that at least one additional exon for the 74 bases long 5' untranslated region in H-protein mRNA exists as the presumable first exon. None of the 5.0- and 5.5-kb SacI and the 5.2-kb EcoRI fragments which were undetectable in the genomes of patients with nonketotic hyperglycinemia was included in the true H-protein gene. PMID- 1872831 TI - Localization of the gene encoding steroid hydroxylase cytochrome P-450 from Rhizopus nigricans inside a HindIII fragment of genomic DNA. AB - The gene encoding steroid inducible cytochrome P450 of Rhizopus nigricans ATCC 6227b has been found inside a HindIII fragment of the genomic DNA by hybridization with a partial length cDNA probe. The latter was isolated by immunoscreening a cDNA library prepared in the lambda gt11 expression system and identified on the basis of inducibility and sequence analysis. The nucleotide sequence of the cDNA probe revealed a coding sequence for the heme binding segment characteristic of the P450 gene family. PMID- 1872832 TI - Oxidative degradation of high molecular weight chlorolignin by manganese peroxidase of Phanerochaete chrysosporium. AB - Phanerochaete chrysosporium was able to degrade high molecular weight chlorolignins (Mr greater than 30,000) from bleach plant effluents, although a direct contact between ligninolytic enzymes and chlorolignin was prevented by a dialysis tubing. In the absence of the enzymes, Mn3+ depolymerized chlorolignin when complexed with lactate causing the color, chemical oxygen demand (COD) and dry weight to decrease by 80%, 60% and 40%, respectively. Manganese peroxidase effectively catalyzed the depolymerization of chlorolignin in the presence of Mn2+ and H2O2. It can be concluded from these results that manganese peroxidase plays the major role in the initial breakdown and decolorization of high molecular weight chlorolignin in bleach plant effluents by P. chrysosporium in vivo. PMID- 1872833 TI - Enhancing effects of human macrophage colony-stimulating factor on the secretion of human chorionic gonadotropin by human chorionic villous cells and tPA30-1 cells. AB - Human macrophage colony-stimulating factor (hM-CSF) concentration-dependently enhanced the secretion of human chorionic gonadotropin (hCG) by primary cultured human cytotrophoblastic cells and a human placental cell line, 3A-SubE (tPA30-1). Since this effect appeared 12 hours after the addition of hM-CSF and disappeared when protein synthesis was inhibited, it was surmised that hCG synthesis was enhanced by hM-CSF. When anti fms (hM-CSF receptor) antibody was added, hCG secretion by cultured human cytotrophoblasts in early pregnancy markedly decreased. These findings demonstrate that hM-CSF acts on the chorionic villous cells and promotes hCG synthesis by these cells. PMID- 1872834 TI - Substrate effects on the enzymatic activity of alpha-chymotrypsin in reverse micelles. AB - Six different substrates have been used for measuring the activity of alpha chymotrypsin in reverse micelles formed by sodium bis(2-ethylhexyl) sulfosuccinate (AOT) in isooctane. The substrates were glutaryl-Phe p nitroanilide, succinyl-Phe p-nitroanilide, acetyl-Phe p-nitroanilide, succinyl Ala-Ala-Phe p-nitroanilide, succinyl-Ala-Ala-Pro-Phe p-nitroanilide and acetyl Trp methyl ester. It has been shown that the dependence of the kinetic constants (kcat and Km) on the water content of the system, on wo (= [H2O]/[AOT]), is different for the different substrates. This indicates that activity-wo profiles for alpha-chymotrypsin in reverse micelles not only reflect an intrinsic feature of the enzyme alone. For the p-nitroanilides it was found that the lower kcat (and the higher Km) in aqueous solution, the higher kcat as well as Km in reverse micelles. "Superactivity" of alpha-chymotrypsin could only be found with the ester substrate and with relatively "poor" p-nitroanilides. The presence of a negative charge in the substrate molecule is not a prerequisite for alpha chymotrypsin to show "superactivity". PMID- 1872835 TI - NG-monomethyl-l-arginine (NMA) restores arterial blood pressure but reduces cardiac output in a canine model of endotoxic shock. AB - Previous studies have suggested that NMA or similar inhibitors of nitric oxide synthesis from L-arginine reverses or prevents the hypotension associated with endotoxin administration. We wanted to determine if vascular and cardiac responses to NMA support the idea that inhibitors of nitric oxide synthesis might be useful in the treatment of septic shock. Pentobarbital-anesthetized beagle dogs were administered endotoxin for 2 hours at a dose of 250 ng/kg/min. This resulted in reductions in systemic vascular resistance (34% decrease) and mean arterial pressure (25% decrease). Administration of NMA (30 mg/kg, IV) caused large and sustained increases in mean arterial pressure and systemic vascular resistance, and a large decrease in cardiac output and femoral arterial blood flow. Although NMA restored arterial pressure, the large and sustained fall in cardiac output suggests that the cardiovascular action of NMA is detrimental to dogs treated with endotoxin. PMID- 1872836 TI - Melibiose permease of Escherichia coli: mutation of aspartic acid 55 in putative helix II abolishes activation of sugar binding by Na+ ions. AB - An aspartic residue (Asp55) located in the putative transmembrane alpha-helix II of the melibiose(mel) permease of Escherichia coli was replaced by Cys using oligonucleotide-directed, site-specific mutagenesis. Although D55C permease is expressed at 0.7 times the level of wild type permease, the mutated mel permease loses the ability to catalyse Na+ or H+ coupled melibiose transport against a concentration gradient. (3H) p-nitrophenyl-alpha-D-galactoside (NPG) binding studies demonstrated that D55C permease binds the sugar co-substrate but Na+ (or Li+) ions do no longer enhance the affinity of D55C permease for the co transported sugar. In addition sugar binding on D55C permease but not on wild type permease is inactivated by sulfhydryl reagents and the inhibition protected by an excess of melibiose. These observations suggest 1) that the negatively charged Asp55 residue, expected to be within the membrane embedded domain near the NH2 extremity of mel permease, is in or near the Na(+)-binding site and 2) that the cation and sugar binding sites may be overlapping. PMID- 1872837 TI - Measuring the balance between insulin synthesis and insulin release. AB - The absolute rates of hormone synthesis and release were determined in purified pancreatic B cells. Newly synthesized proteins were labeled with L-[3,5 3H]tyrosine or L-[2,5-3H]histidine. When medium glucose was less than or equal to 10 mM, the production of insulin exceeded or equaled its release. Raising the glucose levels above 10 mM did not further increase the rate of insulin synthesis (67 +/- 10 fmol/10(3) cells/2 hour) but elevated that of insulin release up to 3 fold the production rates (181 +/- 10 fmol/10(3) cells/2 hour). In the presence of glucagon or of the phorbol ester 12-O-tetradecanoylphorbol 13-acetate the cells also released 3-fold more hormone that they synthesized; release was however reduced to 25% of the rate of production in the presence of epinephrine. It is concluded that glucose as well as hormonal regulators of islet B cells can influence, bi-directionally, the balance between the rates of insulin synthesis and release. PMID- 1872838 TI - Individual alpha and beta subunits of bacterial luciferase exhibit bioluminescence activity. AB - The alpha subunit of luciferase, encoded by the luxA gene, and the beta subunit, encoded by the luxB gene, have been expressed independently in Escherichia coli. We have found that the individual subunits of the heterodimeric (alpha beta) enzyme have bioluminescence activity. Overexpression of the individual subunits in Escherichia coli at 37 degrees resulted in accumulation of large amounts of the specific subunit in the insoluble fraction, while expression at lower temperatures (20 degrees-26 degrees) resulted in accumulation of high levels of the individual subunits in the soluble fraction of the cell lysates. We were surprised to find that addition of n-decanal to extracts of cells carrying either the luxA gene or the luxB gene followed by injection of FMNH2, conditions of the standard luciferase assay, resulted in emission of significant bioluminescence. The occurrence of the activity in lysates of E. coli cells carrying the gene for only one subunit showed that the activity of the isolated subunits is not due to contamination of one subunit with trace amounts of the other. The observed bioluminescence activity is the result of reactions catalyzed by the alpha subunit in the absence of beta subunit and also by the beta subunit in the absence of the alpha subunit. PMID- 1872839 TI - The Drosophila glutathione S-transferase 1-1 is encoded by an intronless gene at 87B. AB - The Drosophila glutathione S-transferase 1-1 is a dimer of a 209 amino acid subunit, designated DmGST1. DmGST1 is encoded by a member of a multigene family. Sequence analysis of a genomic clone for GST1 revealed that it is encoded by an intronless gene. We designate this gene and its other family members the GST D genes in the glutathione S-transferase gene superfamily. The Drosophila GST D genes are mapped by in situ hybridization to chromosome 3R at 87B of the polytene chromosome, which is flanked by the two clusters of hsp70 genes at 87A7 and 87C1. Cytogenetic data in the literature indicated that a puff occurred in this region under heat shock. We report that the glutathione S-transferase activity in Kco cells as determined by conjugation with 1-chloro-2,4-dinitrobenzene is elevated slightly to two-fold under heat shock. The implication of this finding is discussed. PMID- 1872840 TI - The primary structure of rat ribosomal protein S18. AB - The amino acid sequence of the rat 40S ribosomal subunit protein S18 was deduced from the sequence of nucleotides in a recombinant cDNA. S18 has 152 amino acids and has a molecular weight of 17,707. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 10-13 copies of the S18 gene. The mRNA for the protein is about 600 nucleotides in length. Rat S18 is identical to mouse S18 (also referred to as KE3) and is related to Escherichia coli S13 and to other S13 like ribosomal proteins from Bacillus subtilis, from Bacillus stearothermophilus, and from plant mitochondria (Nicotiana tabacum and Zea mays). PMID- 1872841 TI - Entactin forms a complex with fibronectin and co-localizes in the extracellular matrix of the embryonal carcinoma-derived 4CQ cell line. AB - A novel extracellular matrix that consists of a complex of fibronectin and entactin was synthesized by the embryonal carcinoma-derived cell line 4CQ. The matrix was devoid of laminin. High steady state levels of the messenger RNAs for fibronectin, entactin, and the B2 chain of laminin were detected in these cells. Laminin B1 message was several fold lower while laminin A chain message was undetectable. In contrast, in the sister embryonal carcinoma-derived cell M1536 B3 there were high levels of message for all three chains of laminin and for entactin but very little for fibronectin. The data suggest that the synthesis and deposition of laminin and fibronectin are inversely related. The direct binding of entactin and fibronectin was also demonstrated by affinity column chromatography and solid phase assay. PMID- 1872842 TI - Functional conversion from HIV-1 Rev to HTLV-1 Rex by mutation. AB - A nucleolar localizing rev gene mutant M10 of human immunodeficiency virus type 1 (HIV-1) lost a Rev function completely, instead, gained a Rex activity of human T cell leukemia virus type 1 (HTLV-1). The obtained compatibility between Rev M10 and Rex with their own nucleolar targeting signal (NOS) suggests a common molecular mechanism of their post-transcriptional regulation, despite no sequence similarities of both proteins and their responsive RNA elements, respectively. PMID- 1872843 TI - Deduced primary structure of a Xenopus proteasome subunit XC3 and expression of its mRNA during early development. AB - Proteasome is a non-lysosomal proteinase complex ubiquitously distributed in eukaryotic cells. We isolated here the cDNA clone for one of the proteasome subunits (XC3) from Xenopus ovary cDNA libraries using rat RC3 cDNA as a prove. The cDNA is 885 bp long and encodes 234 amino acids. The deduced amino acid sequence is highly homologous (95.3%) to those of rat RC3 and human HC3 subunits. The mRNA for XC3 is one of the maternal mRNAs and detected at all the embryonic stages investigated, but its level changes in a characteristic way especially at the gastrula stage. We suggest that the highly conserved XC3 subunit plays an essential role in proteasome function and also that during Xenopus embryogenesis mRNA for XC3 subunit is replaced from maternal to newly-synthesized one probably around the gastrula stage. PMID- 1872844 TI - Transfer RNA lacking its 3' terminus is required for spermidine-dependent ribonuclease 65 activity in mouse FM3A cell extracts. AB - A spermidine-dependent endoribonuclease (designated as RNase 65) activity requires both RNA and protein components (Nashimoto et al. (1991) Biochem. Biophs. Res. Comm. 176:1163-1169). In this study, we fractionated RNAs from mouse FM3A cell extracts and showed that an RNA fraction containing two major RNAs and two minor ones restored the micrococcal nuclease-inhibited RNase 65 activity. Partial sequences of these four RNA species were determined by chemical RNA sequencing. A sequence homology search revealed that the two major RNAs were glutamine tRNA lacking its 3' terminus, and that the two minor RNAs were initiator methionine tRNA and glycine tRNA lacking their 3' termini. PMID- 1872845 TI - Carbohydrate analysis of human von Willebrand factor with horseradish peroxidase conjugated lectins. AB - Human von Willebrand factor (vWF) immobilized on a polyvinylidene difluoride membrane was subjected to binding assay with a series of horseradish peroxidase conjugated lectins. The protein was reactive with concanavalin A, Ricinus communis agglutinin 120, wheat germ agglutinin and Ulex europaeus agglutinin I (UEA-I) but not with peanut agglutinin before sialidase treatment. These reactivities were consistent with the major oligosaccharide structure reported except for UEA-I. The reactivity with UEA-I was greatly decreased after digestion of the protein with either alpha-L-fucosidase or peptide-N-glycosidase F, but no significant decrease was observed after mild alkaline treatment or delipidation. vWF and UEA-I have been independently used as a good marker for human endothelial cells. Our results indicate that vWF itself contains UEA-I reactive sugar chains in its Asn-linked oligosaccharides. PMID- 1872846 TI - Identification of the peroxidation product hydroxystearic acid in Lewis lung carcinoma cells. AB - Whole cell lipids were extracted from the Lewis lung carcinoma in vitro line C108. The fatty acids were derivatized to methylesters in order to identify endogenous oxidized derivatives by gasmass spectroscopy. The presence of 9 hydroxystearic acid and 10-hydroxystearic acid was thus evidenced for the first time in cultured mammalian cells. Moreover a linear correlation was found between the concentration of these products expressed as percentage of total fatty acid methylesters and the cell density in tissue culture flasks. This finding suggests an involvement of hydroxystearic acid in cellular functions related to the cell density in monolayer cultures. PMID- 1872847 TI - Photoisomerization of retinal at 13-ene is important for phototaxis of Chlamydomonas reinhardtii: simultaneous measurements of phototactic and photophobic responses. AB - A real-time automated method was developed for simultaneous measurements of phototactic orientation (phototaxis) and step-up photophobic response of flagellated microorganisms. Addition of all-trans retinal restored both photoresponses in a carotenoid-deficient mutant strain of Chlamydomonas reinhardtii in a dose-dependent manner. The phototactic orientation was biphasic with respect to both the light intensity and the concentration of retinal. All trans retinal was more effective than 11-cis retinal to regenerate both photobehavioral responses. Analogs having locked 11-cis configurations and a phenyl ring in the side chain also induced photoresponses, although at concentrations more than two orders of magnitude higher than all-trans retinal. According to the present assay method, the responses were hardly detectable in cells incubated with retinal analogs in which the 13-ene was locked in either its trans or cis configuration. The results strongly suggest that the isomerization of the 13-14 double bond is important for photobehavioral signal transduction and that a single retinal-dependent photoreceptor controls both phototactic and photophobic responses. PMID- 1872848 TI - Scanning tunnelling microscopy of 16S ribosomal RNA in water. AB - The scanning tunnelling microscope has been used to image 16S ribosomal RNA molecules in water electrophoretically deposited on graphite surface. Two kinds of images have been obtained: images showing aggregates of 16S ribosomal RNA molecules similar to those obtained from DNA solutions and others showing individual 16S ribosomal RNA molecules. An interesting characteristic of these images, recorded in constant current mode, is that the 16S ribosomal RNA molecules appear to be located below the graphite surface. The morphology and several structural parameters of the molecules were consistent with the data obtained from electron microscopy. PMID- 1872849 TI - Sequence analysis of the ryanodine receptor: possible association with a 12K, FK506-binding immunophilin/protein kinase C inhibitor. AB - A computer-assisted sequence analysis of the ryanodine receptor pointed to a 15 residue peptide, "KC7", reported to have been purified from a proteolytic digest of the 565 kDa rabbit skeletal muscle protein. Sequence comparisons, however, showed that this peptide probably originated from a much smaller protein which copurified with the ryanodine receptor. Peptide KC7 (excluding its unknown N terminal residue) was identical to the N-terminus of a 12 kDa immunophilin (immunosupressant-binding protein), human T-cell FK506- binding protein (FKBP), which has recently been identified as an inhibitor of protein kinase C. There was no other sequence similarity between FKBP and the ryanodine receptor. It is suggested that in vivo interaction of the ryanodine receptor and FKBP may play a role in the modulation of calcium release in muscle. PMID- 1872850 TI - Type II phospholipase A2 recombinant overexpression enhances stimulated arachidonic acid release. AB - The coding sequence of type II phospholipase A2 from human placenta was cloned in a bovine papilloma virus-derived eukaryotic expression vector under the control of the metallothionein promoter. Stably transfected C127 mouse fibroblast lines were obtained with this vector. These transfected cells overexpressed a functional 14 kDa phospholipase A2, which was bulky secreted. However, a significant phospholipase A2 activity was measured in cell homogenates. The involvement of this 14 kDa phospholipase A2 in mechanisms related to stimulated arachidonic acid release was investigated. We could parallel the overexpression of phospholipase A2 with an increase in phorbol ester and fluoroaluminate stimulated arachidonic acid release. Pertussis toxin inhibited this stimulation. These results suggest that the 14 kDa type II phospholipase A2 might contribute to stimulation of arachidonic acid release, and therefore to eicosanoid production. PMID- 1872851 TI - Halo enol lactone inhibitors of chymotrypsin: burst kinetics and enantioselectivity of inactivation. AB - Burst kinetics in the inactivation of alpha-chymotrypsin by halo enol lactones 1 and 2 was observed. These results are consistent with a kinetic scheme that includes partitioning of the first acyl enzyme between transient inhibition and permanent inactivation. Partition ratios were estimated from the measured rates of the irreversible inactivation and the rates of deacylation of the second acyl enzyme. Halo enol lactones with a large burst resulted in small partition ratios, indicating a high potency of inactivation. We also observed enantioselectivity in the burst of inactivation such that the R enantiomer of lactone 1 showed a large burst, while the S enantiomer showed a little burst. This suggests that it is the R enantiomer whose binding is better suited for the covalent derivatization of the enzyme, or whose reactive halomethyl group is in an unfavorable position for the hydrolysis by water. PMID- 1872852 TI - The presence of N-glycosylated proteins in cell nuclei. AB - The protein-DNA crosslinking capability of cis-dichloro diammineplatinum has been exploited to check the intranuclear location of N-glycosylated proteins. When intact liver cells were treated with this reagent, a number of glycoproteins, recognized by Concanavalin A, have been shown to become crosslinked to DNA; many of them have been recognized as nuclear matrix components. The recognition by this lectin was abolished by treatment with N-glycosidase F, showing the presence of N-glycosidic bonds between the sugar moiety and the protein. Most of the glycoproteins appeared to have high mannose oligosaccharide chains, but sialic acid containing oligosaccharides were also identified. PMID- 1872853 TI - Human liver class III alcohol and glutathione dependent formaldehyde dehydrogenase are the same enzyme. AB - Human liver class III alcohol dehydrogenase (chi chi-ADH) and glutathione dependent formaldehyde dehydrogenase are the same enzyme. The enzyme, chi chi ADH, exhibits a kcat of 200 min-1 and a km of 4 microM for the oxidation of formaldehyde, but only in the presence of GSH. In the absence of GSH the enzyme is essentially inactive toward formaldehyde but very active toward long chain alcohols. Thus, as in the rat (Koivusalo, M., Baumann, M., and Uotila, L. (1989) FEBS Letters 257, 105-109), the class III alcohol dehydrogenase and the GSH dependent formaldehyde dehydrogenase are identical enzymes. S-Hydroxymethyl derivatives of 8-thiooctanoate and lipoate are also very active substrates. The activity is specific for class III alcohol dehydrogenase; neither the class I and II nor the horse EE, ES, and SS isozymes oxidize hemithiolacetals. o Phenanthroline competitively inhibits both activities and the two substrate types compete with each other. PMID- 1872854 TI - Lysophosphatidylcholine as a possible second messenger synergistic to diacylglycerol and calcium ion for T-lymphocyte activation. AB - An immediate reaction product of phosphatidylcholine hydrolysis catalyzed by phospholipase A2, lysophosphatidylcholine (lysoPC), synergizes with a membrane permeable diacylglycerol, 1,2-dioctanoylglycerol, and ionomycin to activate resting T-lymphocytes as measured by interleukin-2 alpha-receptor expression. It is suggestive that both phospholipase C and phospholipase A2 are directly involved in signal transduction in a synergistic fashion and that lysoPC acts as an additional second messenger for cellular regulation, probably for long-term responses such as cell proliferation and differentiation. PMID- 1872855 TI - Initial characterization of the carbohydrate structure of MCP-1. AB - MCP-1 is the principle monocyte chemoattractant produced by tumor cells in vitro. We previously identified different isoforms of MCP-1. Here we report that two predominant isoforms of MCP-1 (13 kD and 9 kD) can be distinguished by lectin binding. The results indicate that the disaccharide galactose-beta 1-3D-N-acetyl galactosamine is present on the 13 kD MCP-1 isoform but not the 9 kD isoform. Glycosylation of the 13 kD MCP-1 isoform does not appear to significantly change its antigenic properties and also does not affect its capacity to induce monocyte migration. PMID- 1872856 TI - Bio-elimination and organ retention profile of benzanthrone in scorbutic and non scorbutic guinea pigs. AB - The retention and bio-elimination of benzanthrone (BA) in scorbutic and non scorbutic guinea pigs was investigated to understand the protective role of ascorbic acid. Oral intubation of 14C-BA to scorbutic and non-scorbutic guinea pigs showed a total recovery of around 91% radioactivity through urine, faeces and tissues. Recovery of radiolabelled BA through urine (28%) and faeces (22%) up to 96 hrs averaged 50%, whereas residual radioactivity in liver and testis experienced a recovery of 29% in scorbutic animals. In non-scorbutic animals there was an increased recovery of radioactivity through urine (37%) and faeces (31%) with a decrease in retention (10%) in liver and testis. These results suggest that ascorbic acid facilitates the mobilization and bio-elimination of BA and thereby can decrease the toxicity of the compound. PMID- 1872857 TI - Characterization of N- and C-terminal deletion mutants of the rat serotonin HT2 receptor in Xenopus laevis oocytes. AB - Deletion mutants of the serotonin HT2 receptor have been constructed in which the N- and C-terminal sequences have been gradually removed. The mutant constructs were assayed for their biological activity by electrophysiological measurements in Xenopus oocytes previously injected with the respective in vitro synthesized cRNAs. No significant loss of biological activity was observed when either the extracellular N-terminal sequence, including all potential glycosylation sites, up to the beginning of the first transmembrane domain or the C-terminal sequence up to cystein residue 397, which is conserved in most G-protein coupled receptor known so far, was deleted from the serotonin HT2 receptor constructs. PMID- 1872858 TI - Study of O-glycan sialylation in C6 cultured glioma cells: evidence for post translational regulation of a beta-galactoside alpha 2,3 sialyltransferase activity by N-glycosylation. AB - We have studied the Gal beta 1-3GalNAc-R alpha 2,3 sialyltransferase from C6 glioma cells transferring Neu5Ac from CMP-Neu5Ac onto O-glycans of glycoproteins. Using synchronized C6 glioma cells, we showed that the alpha 2,3 sialyltransferase activity was inhibited by tunicamycin to a greater extend than DNA and protein biosynthesis suggesting inhibition of N-glycosylation of this enzyme. Additional demonstration of N-glycosylation of the alpha 2,3 sialytransferase was provided through ConA-Sepharose binding. Treatment of partially purified alpha 2,3 sialytransferase by peptide-N-glycosidase F showed a significative inhibition demonstrating that N-glycan moiety is required for complete activity of the C6 glioma cell alpha 2,3 sialyltransferase. PMID- 1872860 TI - An endonuclease activity in human polymorphonuclear neutrophils that removes 8 hydroxyguanine residues from DNA+. AB - An endonuclease that specifically removes 8-hydroxyguanine (oh8Gua) from DNA has been isolated from Escherichia coli. As the amount of oh8Gua produced in DNA of X ray-irradiated mice is known to decrease with time after irradiation, an attempt was made to find a similar activity in human polymorphonuclear neutrophils (PMNs) using a synthetic dsDNA containing oh8Gua as a substrate. The PMN enzyme was isolated free of other DNases, and found to cleave the substrate DNA simultaneously at 2 sites, the phosphodiester bonds 5' and 3' to oh8Gua, producing free hydroxyl and phosphate groups, respectively. The enzyme showed almost no activity on DNAs containing other kinds of modified base tested or mismatched DNA. Thus human cells also contain an endonuclease that specifically removes oh8Gua residues from DNA. PMID- 1872859 TI - Stimulation of autocrine platelet--derived growth factor AA-homodimer and transforming growth factor beta in vascular smooth muscle cells. AB - We have investigated the interrelationship between growth factors and vasoconstrictor peptides in terms of their possible paracrine/autocrine regulation of vascular smooth muscle cell differentiation/proliferation. Responses of quiescent cells from spontaneously hypertensive and Wistar-Kyoto rats to stimulation with a selected number of growth factors- and vasoconstrictor peptides were established (induction of mRNA as well as secretion of immunoreactive peptides). A single exposure of quiescent vascular smooth muscle cells to the vasoconstrictor peptides Angiotensin II and Endothelin-1 (10(-8) M each) resulted in a prolonged induction of platelet- derived growth factor A chain and transforming growth factor beta transcripts (maximal at 5-6 hrs poststimulatory). The interrelationship between platelet- derived growth factor AA and transforming growth factor beta was investigated in experiments using the pure peptides individually for stimulation of mRNA and peptide secretion. Both growth factors enhanced their own and one anothers transcript expression. The results demonstrated that in spontaneously hypertensive rats, an established animal model of hypertension, the steady state balance of this set of growth factors may be disturbed. Defects involved may be attributable to alterations in the secretory machinery and/or amount of autocrine growth factor produced. PMID- 1872861 TI - Detection of 14-kDa group II phospholipase A2 in human seminal plasma. AB - About 90% of phospholipase A2 activity detected in human seminal plasma reacted with monoclonal antibodies raised against human synovial fluid phospholipase A2. The crude seminal plasma yielded a pure immuno-cross-reactive phospholipase A2 preparation in a single purification step using immuno-affinity chromatography. The amino acid sequence of the N-terminal 20 residues of this seminal enzyme was determined and found to be identical with that of human synovial phospholipase A2. Thus, it is suggested that human seminal plasma contains phospholipase A2, belonging to the 14-kDa group II enzyme family, as the major isoenzyme. PMID- 1872862 TI - Interaction of human protein Z with thrombin: evaluation of the species difference in the interaction between bovine and human protein Z and thrombin. AB - Protein Z is a vitamin K-dependent protein of unknown function present in normal human and bovine plasma. Binding and kinetic studies showed that bovine protein Z interacts with bovine thrombin with a dissociation constant of 0.11 microM in a Ca(2+)-independent fashion and that thrombin becomes associated with phospholipid vesicles in the presence of protein Z but not in its absence (Hogg, P. J. and Stenflo, J. (1991) J. Biol. Chem., in press). In the present study the interaction of human protein Z with human thrombin and the influence of human protein Z on the association of thrombin with phospholipid vesicles was evaluated. In contrast to bovine protein Z, human protein Z bound human DIP thrombin with a 20-fold weaker affinity at 1.5 mM Ca2+ and in a Ca(2+)-dependent fashion. Human protein Z was also less effective than bovine protein Z in promoting the association of thrombin with phospholipid vesicles. Also, bovine protein Z cleaved by thrombin at Arg-365 bound DIP-thrombin with a 10-fold weaker affinity than did native bovine protein Z. The data suggest that the species difference in the interaction between protein Z and thrombin can be explained by a difference in the COOH-terminal region of bovine protein Z versus human protein Z. PMID- 1872863 TI - Spermidine regulation of ornithine decarboxylase synthesis by a GC-rich sequence of the 5'-untranslated region. AB - The nucleotides in the 70-170 region upstream from the initiator AUG have been shown to be important in the strong stimulation of ornithine decarboxylase (ODC) synthesis by low spermidine concentrations and in the inhibition of ODC synthesis at high spermidine concentrations [Ito, K., et al. (1990) J. Biol. Chem. 265, 13036-13041]. In this region, a GC-rich sequence as well as a small open reading frame (MGQASQATVL) existed. In order to clarify which of these was of greater importance for the spermidine regulation of ODC synthesis, the synthesis was performed with various ODC mRNAs, possessing different sizes and nucleotide sequences in the 5'-untranslated region. The results show that a GC-rich sequence, but not a small potential leader peptide, plays an important role in the spermidine regulation of ODC synthesis. PMID- 1872864 TI - Conclusive evidence that very-long-chain fatty acids are oxidized exclusively in peroxisomes in human skin fibroblasts. AB - We have investigated the contribution of peroxisomes and mitochondria to the beta oxidation of palmitate (C16:0) and cerotate (C26:0) in intact human skin fibroblasts. The oxidation of both fatty acids was found to be inhibited by rotenone plus antimycin and cyanide, respectively, although to a different extent. When 2-[5-(4-chlorophenyl)pentyl]-oxirane-2-carboxylate (POCA) was used to specifically block carnitine palmitoyltransferase I, it was found that palmitate beta-oxidation was inhibited almost completely whereas cerotate beta oxidation was not affected. Since carnitine palmitoyltransferase is essential for the oxidation of fatty acids in mitochondria this result provides conclusive evidence that oxidation of very-long-chain fatty acids is initiated in peroxisomes and not in mitochondria. PMID- 1872865 TI - Identification of a soluble enzyme from C3H/10T1/2 cells which is inhibited by the Bowman-Birk proteinase inhibitor. AB - The anticarcinogenic Bowman-Birk proteinase inhibitor (BBI) inhibits a 70-kDa serine proteinase in C3H/10T1/2 transformed fibroblasts. Two serine proteinases, the proline endopeptidase and a novel neutral proteolytic activity, both having a mass of approximately 70-kDa, were isolated from the cytoplasm of C3H/10T1/2 cells. BBI did not inhibit diisopropylfluorophosphate binding to the proline endopeptidase or its ability to hydrolyze peptides. However, BBI blocked the binding of diisopropylfluorophosphate and inhibited the cleavage of peptides by the novel cytoplasmic enzyme. Thus BBI does not inhibit the proline endopeptidase but another soluble 70-kDa serine proteinase from C3H/10T1/2 cells. PMID- 1872866 TI - Effect of coherence time of the applied magnetic field on ornithine decarboxylase activity. AB - Skepticism over the possibility of weak electromagnetic fields affecting cell function exists because endogenous thermal noise fields are larger than those reported to cause effects. Four-hour exposure to a 55- or 65-Hz field approximately doubles the specific activity of ornithine decarboxylase (ODC) in L929 cells. To test the idea that the cell discriminates against this thermal noise because it is incoherent, partial incoherence was introduced into the applied field by shifting the frequency between 55- to 65-Hz at intervals of tau coh--delta tau where tau coh is a predetermined time interval and delta tau much less than tau coh varies randomly from one frequency shift to the next. To obtain the full ODC enhancement, coherence of the impressed signal must be maintained for a minimum of about 10s. For tau coh = 5.0s a partial enhancement is elicited, and at 1.0s there is no response. Unfortunately coherence times of this duration are too short to solve the thermal noise puzzle. PMID- 1872867 TI - Effect of 17 beta-estradiol on the proliferation of osteoblastic MC3T3-E1 cells via human monocytes. AB - Effects of human monocyte-conditioned medium on the proliferation of osteoblastic MC3T3-E1 cells were investigated in serum-free cultured condition. Monocyte conditioned medium significantly stimulated osteoblast proliferation at the concentration between 10 and 30%, compared to that in the absence of monocytes. 17 beta-estradiol directly stimulated osteoblast proliferation at the concentrations of 10(-8) and 10(-10)M. On the contrary, the conditioned medium prepared by monocytes cultured in the presence of 17 beta-estradiol at the concentrations of 10(-8) and 10(-10)M significantly inhibited osteoblast proliferation. Present data indicate that in addition to direct effect on osteoblasts, 17 beta-estradiol affected osteoblast proliferation presumably through modulating the release of several local regulators of bone turnover from monocytes. The effect on osteoblastic activity via monocytes might be linked to the coupling of osteoclast and osteoblast actions. PMID- 1872868 TI - The rate of phosphate transport during recovery from muscular exercise depends on cytosolic [H+]. A 31P-MR spectroscopy study in humans. AB - 31-Phosphorus magnetic resonance spectroscopy was used to study in vivo the effect of cytosolic [H+] on the kinetics of initial post-exercise recovery of inorganic phosphate (Pi) in human gastrocnemius muscle. Linear correlations were found between the rate of initial phosphate recovery and: a) the minimum value of cytosolic pH reached during recovery, and b) the minimum percentage of divalent anion present. These linear relationships are consistent with the current knowledge of Pi transport, and represent new invariant parameters for the study of muscle pathologies that may involve Pi and/or H+ transport. PMID- 1872869 TI - Different translocation of three distinct PKC isoforms with tumor-promoting phorbol ester in human platelets. AB - Protein kinase C (PKC), a family of related but distinct enzymes whose cellular functions are poorly understood, acts in synergy with Ca2+ mobilization for the activation of platelets. Using specific antibodies for the different isoforms, immunoblot analysis revealed the presence in human platelets of three different PKC subtypes which specifically react with alpha, beta and zeta-PKC antibodies. Whereas the subcellular distribution of the alpha PKC remained unaffected, incubation of platelets with 1 microM PMA for 2 min resulted in a significant subcellular distribution from cytosol to membrane of beta-PKC (25%) and zeta (15%). The beta-PKC isoform is more sensitive than alpha and zeta-PKC to PMA, since 100 nM PMA resulted in a translocation of 85%, 64% and 66% respectively of a maximum translocation observed with 1 microM PMA. PMID- 1872870 TI - Inhibition by L-arginine of the endothelin-mediated increase in cytosolic calcium in human neutrophils. AB - The effect of endothelin (ET) on the cytosolic-free calcium [(Ca2+]i) changes in polymorphonuclear leukocytes (PMN) from normal humans and Wistar rats was investigated. ET induced a dose-related [Ca2+]i peak. This [Ca2+]i transient was blunted by TMB-8 (10(-5)M) and by Ca(2+)-free EGTA medium, therefore suggesting a role of both intracellular Ca2+ release and Ca2+ influx in the generation of the [Ca2+]i peak. Preincubation of PMN with the nitric oxide (NO)-donor L-arginine (L Arg) markedly blocked the ET-induced [Ca2+]i transient in an enantiomerically specific manner. A similar blunting effect of L-Arg on the fMLP (10(-7)M)-induced [Ca2+]i transient was detected. The L-Arg antagonist, NG-monomethyl-L-arginine (L NMMA), reverted the L-Arg blocking effect on both ET- and fMLP-induced [Ca2+]i transients. These data suggest that ET has a potential role in activating Ca2+ mobilization in PMN, an effect that can be inhibited by L-Arg. PMID- 1872871 TI - Cleavage of phosphorylase kinase and calcium-free calmodulin by HIV-1 protease. AB - Phosphorylase kinase and calcium-free calmodulin are digested by human immunodeficiency virus-1 protease. In phosphorylase kinase, the alpha subunit is preferentially hydrolyzed at arg748-val749. The beta subunit is cleaved only slowly at leu678-pro679, and calmodulin, the integral delta subunit of phosphorylase kinase, is not cleaved at all. However, free calmodulin in the calcium-depleted form showed to be a good substrate for the protease. Here the cleavage occurs at phe65-pro66 and met71-met72. This fast hydrolysis of free calmodulin can be blocked by micromolar concentrations of Ca2+ or millimolar concentrations of Mg2+. PMID- 1872872 TI - Conversion of big endothelin-1 to endothelin-1 by two-types of metalloproteinases of cultured porcine vascular smooth muscle cells. AB - Incubation of big endothelin-1 (big ET-1, 1-39) with the membrane fraction obtained from cultured vascular smooth muscle cells (VSMCs) resulted in an increase in immunoreactive-ET (IR-ET), which was inhibited by EDTA but not by phosphoramidon, a metalloproteinase inhibitor. When the incubation was performed in the presence of N-ethylmaleimide (NEM), the generation of IR-ET was markedly augmented and this augmentation was abolished by phosphoramidon. The pH profile for IR-ET generation in the presence of NEM was apparently distinct from that observed in the absence of NEM. Reverse-phase HPLC of the incubation mixture with or without NEM revealed one major IR-ET component corresponding to the elution position of synthetic ET-1 (1-21). When the cultured VSMCs were incubated with big ET-1, a conversion to the mature ET-1 was observed. This ET-1 generation from exogenously applied big ET-1 was markedly inhibited by the addition of phosphoramidon, although the inhibitor did not influence the basal secretion of ET-1-like materials. These results suggest the presence of two types of metalloproteinases, which can generate ET-1, in VSMCs. The possibility that ET-1 functions in an autocrine manner to control the cardiovascular system warrants further attention. PMID- 1872873 TI - End-filling of an oligonucleotide duplex containing an MDBP site in the human HSP70 promoter inhibits protein-DNA complex formation. AB - A site from the promoter region of the human hsp70 gene binds with a high affinity to the ubiquitous mammalian protein called methylated DNA-binding protein (MDBP) when it is present in a CpG-methylated oligonucleotide duplex with only 14 base-pairs. Binding to this site is dependent upon CpG methylation. Surprisingly, when the same methylated sequence is present in a duplex that has 22 or more base-pairs, binding to this protein is greatly inhibited. Such a requirement for a short duplex region is seen only in certain of the cytosine methylation-dependent binding sites for this protein and is proposed to reflect differences in the conformation of the duplex due to small differences in the nucleotide sequence. PMID- 1872874 TI - Evidence for isoleucine as a positive effector of the ilvBN operon in Salmonella typhimurium. AB - Concerted efforts were directed towards understanding the control of acetohydroxy acid synthase (AHAS) in the gyrB mutant hisU1820 of Salmonella typhimurium. A media shift from valine to valine plus isoleucine causes a dramatic 4 to 5 fold burst of AHAS valine sensitive activity which appears to be dependent on translation. DJ19, an isolated valine sensitive derivative of the gyrB mutant, maintains a dramatic increase in AHAS valine sensitive activity upon the addition of isoleucine to valine supplemented cultures, suggesting that the isoleucine effect is specific for valine sensitive AHAS. Evidence supports isoleucine as a positive effector on valine sensitive AHAS expression and that the gyrB mutation accentuates the isoleucine effect. PMID- 1872875 TI - Direct inhibitory effect of amino-terminal parathyroid hormone fragment [PTH(1 34)] on PTH secretion from bovine parathyroid primary cultured cells in vitro. AB - We have examined the possibility of direct inhibitory effect of PTH(1-34) on PTH secretion in bovine parathyroid cells. As low as 10(-12) M PTH(1-34) completely inhibited low calcium (0.5 mM Ca2+)-stimulated PTH secretion by these cells. In the presence of 1.25 mM Ca2+, 10(-12) M PTH(1-34) inhibited PTH secretion by about 14.3% of the basal value, while 10(-11) M or higher concentration of PTH(1 34) showed potent inhibitory effects equivalent to the inhibitory action of high calcium concentration (2.5 mM Ca2+) on PTH secretion. At 2.5 mM Ca2+, as much as 10(-9) M PTH(1-34) failed to inhibit PTH secretion further. These results suggest that PTH(1-34) might directly, not via calcium concentration, inhibit PTH secretion by parathyroid cells and that a cooperative mechanism could exist between calcium and PTH(1-34) to inhibit PTH secretion. PMID- 1872876 TI - Deregulation of alternative processing of Calcitonin/CGRP-I pre-mRNA by a single point mutation. AB - The Calcitonin/CGRP-I (CALC-I) gene was one of the first examples of a cellular gene exhibiting alternative, tissue-specific processing of its primary transcript. Calcitonin (CT) mRNA is the predominant product in thyroid C-cells, whereas CGRP-I (Calcitonin Gene Related Peptide-I) mRNA is the main product in neurons of the central and peripheral nervous systems. Investigating the molecular mechanism underlying the alternative processing events, we have demonstrated that the CT-specific splice acceptor site is an intrinsical weak site due to usage of a uridine branch acceptor. The data presented in this report show that a single point mutation changing the uridine branch acceptor into a commonly preferred adenosine residue results in the predominant production of CT mRNA in otherwise CGRP-I mRNA-producing F9 cells. The results of the experiments implicate that the low efficiency of CT splicing, caused by usage of a uridine branch acceptor, allows the production of CGRP-I mRNA in neural cells. PMID- 1872877 TI - Effect of the interferone inducer, polyriboinosinic.polyribocytidylic acid on rat liver regeneration following partial hepatectomy. AB - The administration of the interferone inducer, polyriboinosinic.polyribocytidylic acid, inhibited the rise of activities of thymidylate synthase and thymidine kinase as well as DNA content in 24 h-regenerating rat liver in a dose dependent manner. The immunoblotting assay showed that the decrease of thymidylate synthase activity was due to inhibition of the induction of the enzyme. Co-administration of putrescine did not affect the inhibitory effect of polyriboinosinic.polyribocytidylic acid. Polyriboinosinic acid did not affect DNA synthesis in rat liver regeneration. PMID- 1872878 TI - Perturbations in carbohydrate metabolism during cypermethrin toxicity in fish, Tilapia mossambica. AB - Sublethal concentrations (0.04 ppm) of cypermethrin induced significant metabolic changes in brain, liver and gill tissues of fish, T. mossambica. While cypermethrin caused depletion in glycogen and pyruvate levels lactate content was elevated in all the tissues. While phosphorylase 'a' and aldolase activity increased, phosphorylase 'b' activity registered a decrease in the present study. A decrease in lactate dehydrogenase activity with increase in lactate levels suggests reduced mobilization of pyruvate into citric acid cycle. Glucose-6 phosphate dehydrogenase activity was also elevated indicating enhanced oxidation through HMP pathway during cypermethrin toxicity. Inhibition of succinate, malate and isocitrate dehydrogenases and cytochrome c oxidase activity indicates impaired oxidation of carbohydrates through citric acid cycle. PMID- 1872879 TI - Cypermethrin induced changes in nitrogen metabolism of fish, Tilapia mossambica. AB - At sublethal concentrations, cypermethrin caused a decrease in total proteins and an increase in free amino acids, protease, alanine aminotransferase and aspartate aminotransferase in liver, brain and gill tissues of Tilapia mossambica. Nitrogen metabolic profiles like ammonia, urea and glutamine were also elevated in all the tissues as a consequence of cypermethrin toxicity. Glutamate dehydrogenase, AMP deaminase and adenosine deaminase activity was also increased in the present study. PMID- 1872880 TI - Gene cloning and nucleotide sequence of SM22 alpha from the chicken gizzard smooth muscle. AB - A full length of cDNA encoding SM22 alpha from chicken gizzard smooth muscle was cloned and sequenced. Cloned cDNA had a total length of 1214bp and contained a single open reading frame which encodes 200 amino acids with a calculated molecular weight 22214. The predicted amino acid sequence was in complete agreement with the sequence determined by Pearlstone et al. using Edman degradation method (J. Biol. Chem. 262:5985, 1987) except for two additional residues, isoleucine and serine at the C-terminus. PMID- 1872881 TI - A new latent arginine esteropeptidase from human submaxillary gland. AB - One of the arginine esteropeptidases in human submaxillary gland was purified from microsomal membranes. The enzyme is inactive in membranes and requires trypsin treatment for its full activation. The trypsin-activated enzyme was purified to homogeneity. Its molecular weight was determined to be 94,000 by SDS polyacrylamide gel electrophoresis. Among various substrates examined, the obtained enzyme exhibited high specific activities toward Tos-Arg-OMe (esterolysis) and D-Ile-Pro-Arg-pNA (amidolysis). The enzyme was inhibited by some serine proteinase inhibitors, whereas inhibitors of other types of proteinases did not affect or only scarcely affected it. The enzyme appears to be distinct from other arginine esteropeptidases previously described. PMID- 1872882 TI - Molecular cloning of the yeast proteasome PRS2 gene identical to the suppressor gene scl1+. AB - The YC7-alpha gene encoding a subunit of yeast proteasomes named PRS2 has been isolated and sequenced. Southern blot analysis after electrophoretic separation of yeast chromosomal DNAs showed that the PRS2 gene is located in chromosome VII, unlike the PRS1 gene for subunit YC1, is located on chromosome XV. Surprisingly, the overall structure of the PRS2 gene was found to be identical to that of the suppressor scl1+ gene restoring the SCL1-1 mutation that suppresses crl3 cycloheximide-resistant, temperature-sensitive lethality. The identity of these two genes indicates that the suppressive role of the scl1+ gene product on crl3 mutation could be attributed to proteasomal function. PMID- 1872883 TI - Isolation of a yeast mutant deficient in pyruvate carboxylase activity. AB - To improve our understanding of the catalytic mechanism and regulatory properties of pyruvate carboxylase (EC 6.4.1.1), an important biotin-dependent enzyme, we have sought to isolate mutants in Saccharomyces cerevisiae which are defective in pyruvate carboxylase activity. One mutant was isolated which was unable to grow on glucose minimal medium unless supplemented with aspartate. Although the enzyme had only 25% of the wild type pyruvate carboxylase activity, Western analysis and RNase protection analysis demonstrated that the mutant gene was expressed at approximately 70% of the wild type level. On the basis of genetic crosses and complementation tests, we have attributed the defect to mutations in the PYC gene encoding pyruvate carboxylase. PMID- 1872884 TI - Differential solubility behaviour in poly(ethylene glycol) solutions of glucose 6 phosphate and 6-phosphogluconate dehydrogenases from bone marrow, reticulocytes and erythrocytes. AB - Precipitation of glucose 6-phosphate dehydrogenase by poly(ethylene glycol) depends on both pH and the source of haemolysate. An increase in pH from 5 to 7 leads to an increase in the polymer concentration required for precipitation. At any pH, polymer concentration needed to precipitate the enzyme increases in the order bone marrow less than reticulocytes less than erythrocytes. This differential behaviour seems to be due to variations on the effect of pH on the state of aggregation and/or differences in the intrinsic solubility of the enzyme present in the three haemolysates. In contrast, precipitation profile of 6 phosphogluconate dehydrogenase only slightly moves towards higher concentrations of PEG when raising the pH from 5 to 7, being similar at each single pH in the three haemolysates. PMID- 1872885 TI - Ubiquinol prevents alpha-tocopherol consumption during liposome peroxidation. AB - In this study we investigated whether alpha-tocopherol can be spared by ubiquinol 3 during autoxidation of multilamellar liposome. A lipophilic azocompound, 2,2' azobis-(2,4-dimethyl-valeronitrile), was chosen to initiate liposome autoxidation. The effect of either alpha-tocopherol, ubiquinol-3, or a mixture of them was compared. Rates of conjugated diene formation and concomitant disappearance of the two antioxidants was measured. Since the inhibition rate constant for the scavenging of peroxyl radical for alpha-tocopherol was higher than that for quinol-3, it was concluded that alpha-tocopherol is regenerated by ubiquinol-3. PMID- 1872886 TI - Comparison of changes in uptake and mucosal processing of iron in short and long term iron depletion. AB - Thirty minutes following an intragastric dose of [59]Fe, rats subjected to short term and long-term iron depletion showed a similar increase in [59]Fe in plasma and a similar decrease in the retention of [59]Fe in mucosal cytosol compared to controls. With both low-iron groups, a two-fold increase in [59]Fe uptake by brush-border membrane vesicles and a six-fold reduction in the [59]Fe incorporated into the ferritin of the mucosal cytosol were observed. These studies indicate that short-term exposure to a low-iron diet triggers changes in both the uptake of iron by the brush-border membrane and the processing of iron within the mucosal cell prior to major changes in body iron status. PMID- 1872887 TI - The effect of maternal diabetes on glycogen metabolism in the embryonic rat. AB - This study examined the effect of maternal hyperglycemia during pregnancy due to streptozotocin-induced diabetes on the synthesis of glycogen in the brain and liver of embryonic and newborn rats. Maternal hyperglycemia (serum glucose 25.3 +/- 0.9 mM) during gestation had no effect compared to controls (5.7 +/- 0.2 mM) on embryonic and newborn glycogen content in liver. In contrast, embryos experiencing hyperglycemia in utero had a two-fold higher brain glycogen content than controls at term; 1.6 mg/g vs. 0.84 mg/g, respectively. Interestingly there was a significant delay in the mobilization of brain glycogen during the immediate postnatal period in the offspring of diabetic mothers and control animals. These results suggest that uncontrolled maternal diabetes during pregnancy may significantly increase the availability of a potentially important local fuel source for the newborn brain: glycogen. PMID- 1872888 TI - Hybridization of rabbit cardiac tropomyosin with nonpolymerizable tropomyosin species. AB - Rabbit cardiac tropomyosin was hybridized with its nonpolymerizable form, produced by treatment with carboxypeptidase A, and with a naturally occurring nonpolymerizable tropomyosin from horse platelets. Hybridization was achieved by heating equimolar mixtures to 60 degrees C in the presence of 10 mM dithiothreitol, followed by recooling. Samples of intact and carboxypeptidase truncated tropomyosins treated in this way show lower viscosities at low ionic strength than predicted assuming random reformation of the coiled coils, suggesting that hybrids formed with one intact COOH-terminus are unable to polymerize normally. Hybridization of cardiac and platelet tropomyosins was detected by observation of the fluorescence of pyrene groups attached to cysteine residues on platelet tropomyosin. PMID- 1872889 TI - N-acetyltransferase polymorphism. Comparison of phenotype and genotype in humans. AB - N-Acetyltransferase (NAT) isoenzymes are encoded at two loci. One locus encodes an NAT which is expressed widely in tissues, does not vary amongst human individuals and is termed monomorphic NAT (mNAT). The second locus encodes an NAT which is termed polymorphic NAT (pNAT), has a distinct tissue distribution and is responsible for the difference in ability between individuals in acetylating certain arylamine (e.g. sulphamethazine) and hydrazine (e.g. isoniazid) drugs which are polymorphic substrates. We describe a simple DNA based method for genotyping individuals for pNAT. The 'fast' NAT allele (F1) and the three 'slow' alleles (S1, S2 and S3) can be distinguished by using PCR with oligonucleotide primers specific for pNAT followed by restriction enzyme digestion of the amplified product. Heterozygotes are easily identified. The genotype of individual Caucasians compares well with the extent of acetylation of sulphamethazine. The allele distribution of the Caucasian population described here differs from that reported after Southern blot analysis of a Japanese population (Deguchi et al., J Biol Chem 265: 12757-12760, 1990). The most frequent allele at the polymorphic nat locus in Caucasians, S1, is absent in the Japanese population. This difference between the two populations is likely to be the basis of the known interethnic variation in acetylator phenotype frequencies. PMID- 1872890 TI - Effect of chronic hypoxia on acetaminophen metabolism in the rat. AB - The effect of chronic hypoxia (10.5% O2 for 8-9 days) on acetaminophen metabolism was studied in vivo or in isolated cell or microsomal systems. Results from in vivo studies with oral administration of acetaminophen showed that in hypoxic rats, the plasma appearance of the drug was delayed and the plasma half-life was increased. Analyses of the area under the curve (AUCoral) showed that this value was higher in hypoxic rats, whereas the rate constants for elimination (kelim) and absorption (kabs) were lower in these animals. Formation of the glucuronide and sulfate conjugates was decreased significantly (P less than 0.05) in hypoxic animals. The calculated volume of distribution (Vd) after an intravenous dose was not different in either group but total clearance (CL) was 35% lower in hypoxic rats. Studies with isolated hepatocytes from both groups revealed that glucuronidation and sulfation were inhibited markedly at low O2 concentrations. The O2 concentrations required for half-maximal production (P50 values) of glucuronide (2.3 microM O2) and sulfate (1.8 microM O2) conjugates in cells from hypoxic animals were lower than for control cells (5.3 microM and 3.9 microM O2 for glucuronide and sulfate conjugates, respectively). Maximal rates of conjugation in cells from hypoxic rats were 60-70% of control rates. Similar decreases in microsomal UDP-glucuronosyltransferase and cytosolic sulfotransferase activities were found in livers of animals exposed to chronic hypoxia. These lower P50 values are consistent with a lower P50 for oxidation of mitochondrial cytochromes in hypoxic cells. In comparison, the P50 for glutathione conjugation (4.1 microM O2) was not statistically different from control (4.6 microM O2), but the maximal rate was 65% higher. The results show that chronic hypoxia causes a change of absorptive processes and decreased glucuronidation and sulfation reactions which affects the disposition of acetaminophen and potentially the disposition of a variety of other exogenous and endogenous compounds. PMID- 1872891 TI - Regulation by 1,4-diamines of the ornithine decarboxylase activity induced by ornithine in perifused tumor cells. AB - Ornithine decarboxylase (ODC) activity of Ehrlich carcinoma cells was increased more than 36-fold after being maintained for 3.5 hr in vitro in a special chamber which allowed continuous perifusion with 0.5 mM ornithine; if incubated in vitro without perifusion the ODC activity was, of course, only 9-fold by the same concentration of ornithine. Ornithine withdrawal from the perifusion medium resulted in a decay of enzyme activity observed after 90 min; this decay was prevented by addition of 55 microM pyridoxal to the medium. The 1,4-diamines putrescine, spermidine, spermine, agmatine, histamine, serotonin, tryptamine, chlorpheniramine and harmaline at 55 microM strongly suppressed ODC induction by 0.5 mM ornithine in perifused Ehrlich ascites cells. Methyl derivatives also behave as strong inhibitors of ODC induction. On the contrary, N-acetylation paralleled with a decrease in the inhibition capacity: 55 microM N-acetyl putrescine, N-acetyl serotonin or N-omega-acetylhistamine suppressed ODC induction by ornithine in 66, 64 and 19%, respectively. The addition to the perifusion medium of the same concentrations of 1,3-diamines (1,3-diaminopropane, 1,3-diamino-2-propanol or the alkaloid gramine) as well as 1,5-diamines (1,5 diaminopentane and the antihistamic doxylamine or cimetidine) failed to suppress the induction of ODC activity by ornithine. Interestingly, 1,4-benzenediamine, which strongly inhibits ODC activity when the induced enzyme is assayed in its presence, did not suppress the induction of the enzyme when both 0.5 mM ornithine and 55 microM 1,4-benzenediamine were present in the perifusion medium. The inhibitory capacity in down-regulating ODC is not due to differences in the diamine uptake by the cells. The results suggest that the N-N distance (6A) and the charge of one amino group are important chemical characteristics for regulatory effects. PMID- 1872892 TI - Effects of RP 52028 and phenobarbital on mRNA levels of inducible and constitutive sex-specific cytochrome P450 isozymes in rat liver. AB - Sex-related differences in basal levels of mRNA coding for various cytochrome P450 isozymes and their inducibility by 1-(2-chlorophenyl)-N-methyl-N-(1 methylpropyl)-3- isoquinoline carboxamide (RP 52028) in comparison to phenobarbital (PB) were investigated in Sprague-Dawley rats. We observed that the inducible isozymes, namely cytochromes P450IIB1/2 and P450IIIA1/2 were barely detectable in non-induced animal livers. On the contrary, mRNAs coding for two constitutive forms of cytochrome, P450IIC7 and IIC11, were expressed at a high level in untreated rats in a sex-dependent manner. Cytochrome P450IIC11 mRNA was present in male rats only whereas P450IIC7 was expressed in both sexes but at a higher level in female rats. RP 52028 had a dose-dependent inducing effect on the P450IIB1/2 and IIIA1/2 isoforms in both sexes. After administration of a high dose (500 mg/kg), this molecule exhibited a pattern of induction similar to that of PB. Increases in the accumulation of these IIB1/2 and IIIA1/2 messengers were correlated with protein data, suggesting that RP 52028, like PB, induces these isozymes mainly through a pretranslational regulatory mechanism. On the other hand, PB and RP 52028 caused only a slight increase, less pronounced than in Wistar rats, in the mRNA level of the constitutive female-predominant P450IIC7, indicating a strain-related difference in inducibility of this isozyme. RP 52028 had no effect on P450IIC11 mRNA level in male rat liver, in contrast to the decreasing effect obtained with PB. Furthermore, the non-correlated changes in P450IIC11 mRNA level and microsomal testosterone 2 alpha-hydroxylase activity after treatment with RP suggests that this molecule modulates the expression of P450IIC11 at a posttranscriptional level only. PMID- 1872893 TI - Involvement of the microtubular system in the endothelin-1 secretion from porcine aortic endothelial cells. AB - The effects of certain microtubule-disrupting agents on endothelin-1 (ET-1) secretion from porcine aortic endothelial cells were studied. When endothelial cells were treated with thrombin (1 unit/mL), a significant increase in ET-1 secretion was detected in the incubation medium, while ET-1 secretion in the medium was diminished when the cells were treated simultaneously with either colchicine or vinblastine (10(-8)-10(-6) M). In such cases, however, the ET-1 content detected in the cells increased dose-dependently in accordance with the concentrations of the microtubule-disrupting agents. The intracellular accumulation of ET-1 was observed both in mitochondrial and microsomal fractions. On the other hand, thrombin produced a significant increase in polymerized tubulin content without affecting the total tubulin content. A thrombin-induced increase in the intracellular Ca2+ concentration of endothelial cells was inhibited by treatment with either colchicine or vinblastine. These results seem to indicate that the microtubular system may play an important role in ET-1 secretion from endothelial cells. PMID- 1872894 TI - Modulation of rat hepatic cytochromes P450 by chronic methapyrilene treatment. AB - The antihistaminic compound methapyrilene (MP) when chronically administered has been shown to be a rat-specific hepatocarcinogen. To examine the effects of chronic MP treatment on the hepatic microsomal cytochromes P450. Fischer 344 rats were gavaged for 10 weeks (5 days on, 2 days off) with either vehicle or 50, 100, or 150 mg MP/kg body weight. Chronic MP treatment was found to have a significant effect on several microsomal enzymatic activities. Small (17-28%) but significant (P less than 0.05) decreases were observed for total P450 levels and the activities of erythromycin N-demethylase (catalyzed by P450IIIA), N nitrosodimethylamine demethylase (catalyzed by P450IIE1) and pentoxyresorufin O dealkylase (catalyzed by P450IIB1). In addition, a relatively large decrease (approximately 80%) was observed for the activity of benzphetamine N-demethylase (representative of P450IIC11) and an induction of about 40% was observed for ethoxyresorufin O-dealkylase (catalyzed by P450IA). The metabolism of testosterone by microsomes isolated from the rats chronically treated with MP indicated that several reactions were compromized. Specifically, testosterone 2 alpha-hydroxylase, indicative of P450IIC11, was reduced greatly (86%), whereas testosterone 6 beta-hydroxylase, reflecting P450IIIA, and testosterone 7 alpha hydroxylase, indicative of P450IIIA1, were affected only slightly by MP treatment (approximately 25%). Immunoblot analyses of the various microsomal samples were performed to determine if chronic MP treatment had direct effects on the level of expression of the cytochromes P450. Decreases in the levels of P450IIIA, IIE1, and IIC11, determined by immunoblot analyses, closely paralleled those observed for their marker catalytic activities. Further studies will be required to determine the mechanism by which MP affects the levels of the cytochromes P450 (i.e. increased degradation or decreased synthesis). PMID- 1872895 TI - Regulation of 5-HT2 receptors in rat cortex. Studies with a putative selective agonist and an antagonist. AB - The phenylisopropylamine derivative 1-(2,5-dimethoxy-4-iodo-phenyl)-2 aminopropane (DOI) has been suggested recently as a selective serotonin2 (5-HT2) receptor agonist. Because of the potential importance of such a tool for investigations of 5-HT2 receptor regulation, receptor binding studies were performed in rats after acute and chronic treatment with DOI, the selective 5-HT2 antagonist ketanserin, or vehicle. Single injections of 5 or 10 mg/kg DOI reduced the Bmax of cortical sites labeled with [3H]1-(2,5-dimethoxy-4-bromo-phenyl)-2 aminopropane and [3H]ketanserin (9-32 or 32-46%, respectively). Chronic daily treatment with DOI (3-9 mg/kg) further down-regulated 5-HT2 sites in cortex identified with either [3H]ketanserin (-60%) or with [3H]DOB (-75%), without altering Kd values or affecting 5-HT1 sites. In vitro addition to the [3H]ketanserin or [3H]DOB binding assay of 10 nM to 1 microM DOI resulted in competitive inhibition, suggesting that down-regulation found in vivo was not secondary to residual drug. Chronic treatment with ketanserin (10 mg/kg) also down-regulated both [3H]ketanserin (-38%) and [3H]DOB (-58%) sites in cortex without charges in 5-HT1 sites. In naive cortex, competition experiments revealed a Ki (nM) for ( +/- )-DOI of 1.7 +/- 0.02 at sites labeled by [3H]DOB, and a KH and KL of 4.8 +/- 1.5 and 53 +/- 2 nM at sites labeled by [3H]ketanserin. These data indicate that in chronic treatment, DOI, like ketanserin, is highly selective for 5-HT2 vs 5-HT1 sites at behaviorally useful doses. However, a representative putative 5-HT2 selective agonist and antagonist have similar effects on 5-HT2 receptors labeled by agonist or antagonist radioligands. PMID- 1872896 TI - Regulation by angiotensin II of phosphate transport in cardiac myocytes. AB - The purpose of this study was to test the hypothesis that angiotensin II (ang II) affects the transport of inorganic phosphate in adult ventricular myocytes. Ventricular myocytes were isolated from Dahl rats and allowed to take up 32P inorganic phosphate (32P-Pi). The intracellular 32P concentration increased rapidly and reached a peak at 5 min. Ang II, 10(-10) to 10(-5) M, produced a significant (P less than 0.05) and concentration-dependent reduction in 32P-Pi uptake that plateaued at 0.1 to 1.0 microM. Ang II at 1 microM produced a 30% reduction in Vmax and a slightly greater reduction in the Km of 32P-Pi uptake, compared to myocytes that were not exposed to ang II. The ang II receptor antagonist saralasin (Sar1-Val5-Ala8-angiotensin II), significantly (P less than 0.05) antagonized the action of ang II on 32P-Pi uptake. TPA (12-O tetradecanoylphorbol-13-acetate) also produced a significant (P less than 0.05) reduction of 32P-Pi uptake, suggesting that protein kinase C is involved in the transduction of ang II effects on intracellular Pi. 32P Efflux from myocytes, pulsed with 32P-Pi and chased with Pi-free medium, was accentuated markedly by ang II; this effect was blunted by saralasin. These data suggest that ang II is capable of regulating total intracellular Pi in the heart via two actions: (i) by inhibiting uptake of Pi into the myocyte, and (ii) by increasing the efflux of phosphates out of the cell. PMID- 1872897 TI - Endotoxin-inducible cytotoxicity in liver cell cultures--I. AB - It is known that rodents challenged with a combination of galactosamine and endotoxin develop a fulminant hepatitis within several hours. Until now, no in vitro correlate for this organ-specific lesion has been described. Here, in-vitro conditions have been developed which allow examination of lipopolysaccharide (endotoxin)-inducible cell injury to hepatocytes. Under these in-vitro conditions (RPMI 1640 supplemented with 10% calf serum, 40% oxygen tension) which require the presence of functionally intact Kupffer cells, a concentration-dependent lactate dehydrogenase release is inducible by different lipopolysaccharides in hepatocyte cultures from Fischer rats. It can be abrogated by polymyxin B. These co-cultures secreted tumor necrosis factor-alpha into the medium upon a lipopolysaccharide stimulus. The presence of a tumor necrosis factor-alpha antiserum reduced the major part of the endotoxin-inducible cytotoxicity. Similarities in vitro and in vivo of the cytotoxic potency of various endotoxin species and the different responsiveness of hepatocytes from two different rat strains support that this co-culture system might be useful for studying endotoxin-inducible lesions in vitro. PMID- 1872898 TI - Comparative cytotoxic effects of acetaminophen (N-acetyl-p-aminophenol), a non hepatotoxic regioisomer acetyl-m-aminophenol and their postulated reactive hydroquinone and quinone metabolites in monolayer cultures of mouse hepatocytes. AB - Toxic effects of acetaminophen (paracetamol, N-acetyl-p-aminophenol, APAP) in monolayer cultures of mouse hepatocytes developed over a period of 18 hr. N Acetyl-m-aminophenol (AMAP) was approximately 10-fold less toxic than APAP, despite the fact that it bound covalently to a greater extent to hepatocyte macromolecules. AMAP did not deplete glutathione to as great an extent as APAP, indicating that their reactive metabolites may bind to different proteins or that oxidative damage in addition to arylation of proteins may be involved in the development of cell death. The toxicity of 3-methoxy-acetyl-p-aminophenol was similar to that of APAP, whereas the other hydroquinone and quinone metabolites were 8-10 times more cytotoxic than APAP. The potencies of these analogs were in the order: acetyl-m-aminophenol-p-benzoquinoneimine greater than or equal to 2,5 dihydroxyacetanilide greater than or equal to 3-methoxy-p-benzoquinone greater than or equal to N-acetyl-p-benzoquinone imine (NAPQI) greater than or equal to acetyl-m-aminophenol-o-benzoquinone greater than or equal to 3-hydroxy-acetyl-p aminophenol. The relative toxic potencies of the hydroquinone and quinone metabolites of AMAP were comparable to that of NAPQI, and do not readily explain the marked difference between the cytotoxic effects of AMAP and APAP. PMID- 1872899 TI - Increased microsomal irreversible binding of phenytoin by valproic acid. AB - Phenytoin is known to be metabolized to form p-hydroxyphenyl-phenyl-hydantoin, possibly via the arene oxide intermediate. The reactive arene oxide may bind to macromolecules irreversibly and cause toxicity. In this study, valproic acid was found to increase the irreversible binding of phenytoin to rat liver microsomes at high concentrations. The effect was similar to that of TCPO and could be reversed by adding glutathione. Valproic acid may increase the hepatotoxicity of phenytoin. PMID- 1872900 TI - Reactivity of flavone acetic acid and its acyl glucuronide. PMID- 1872901 TI - Effect of ethanol feeding on fatty acid ethyl ester synthase activity in the liver and pancreas of rats fed a nutritionally adequate diet or a low protein diet. PMID- 1872902 TI - Broad-spectrum anti-DNA virus and anti-retrovirus activity of phosphonylmethoxyalkylpurines and -pyrimidines. PMID- 1872903 TI - Electrically-evoked catecholamine release from cat adrenals. Role of cholinergic receptors. AB - Catecholamine (CA) release from perfused cat adrenal glands was continuously monitored using an on-line system coupled to an electrochemical detector. This highly sensitive procedure allowed the detection of small changes in the rate of secretion, even using short trains of electrical stimulation or brief acetylcholine (ACh) pulses. CA release was linear with increasing strength of ACh, transmural or splanchnic nerve stimulation. By using specific blockers, the contribution of nicotinic or muscarinic receptors to the overall secretory response to various stimuli could be established. That nicotinic receptors play a major role in mediating the secretory response to all stimuli is shown by the clear inhibition of the response with mecamylamine (10 microM). In contrast, atropine (1 microM) halved secretion evoked by ACh or nerve stimulation but had little effect on the response to trains of transmural electrical stimulation. When transmural electrical stimulation was applied continuously (instead of in trains), increasing the frequency in a step-wise manner, a bell-shaped curve was obtained; secretion reached a peak at 8 Hz and then declined sharply at 16 and 32 Hz. With this stimulation pattern, atropine decreased by 50% the secretion response at the higher frequencies (4-32 Hz). Very few studies are available which define the role of receptors and ionic channels in mediating electrically evoked CA release. These stimulation patterns have not been used previously and are likely to mimic more closely than those used in earlier studies the physiologic firing pattern of splanchnic nerves innervating adrenomedullary cells. PMID- 1872904 TI - The effects of assay temperature on the complex kinetics of acetaldehyde oxidation by aldehyde dehydrogenase from human erythrocytes. AB - Several studies have shown preparations of the cytosolic aldehyde dehydrogenase (EC 1.2.1.3) from sheep and human liver and from human erythrocytes to exhibit complex kinetic behaviour in which the dependence of the initial velocity on the concentration of acetaldehyde gives rise to downwardly curving double-reciprocal plots. This behaviour has often been analysed in terms of a sharp discontinuity in the double-reciprocal plots and its possible implications for the oxidation of acetaldehyde and other pharmacologically important aldehydes has been a subject of speculation. In the present work, it is shown that the purified, apparently homogeneous, enzyme from human erythrocytes exhibits such complex kinetic behaviour when initial rates are determined at 25 degrees, although the double reciprocal plots describe a smooth curve with no sharp discontinuity. However, when the assays were performed at 37 degrees there was no significant deviation from Michaelis-Menten kinetics over a wide range of acetaldehyde concentrations (0.2-30 mM). At higher concentrations of acetaldehyde inhibition occurred which was competitive with respect to NAD+. These results, which indicate that the complex kinetic behaviour of aldehyde dehydrogenase is not important at physiological temperature, are interpreted in terms of the mechanisms that have been advanced to explain the phenomena. PMID- 1872905 TI - Inhibition of carrageenan-induced paw edema by superoxide dismutase that binds to heparan sulfates on vascular endothelial cells. AB - The effect of heparin-binding superoxide dismutase (HB-SOD), a fusion gene product consisting of human Cu/Zn-SOD and a C-terminal basic domain with high affinity for heparin-like proteoglycans, was examined on carrageenan-induced paw edema in mice and rats. When injected intravenously to mice just before carrageenan, HB-SOD suppressed significantly paw edema. ED30 of HB-SOD (1000 units/kg) was markedly lower than that of SOD (bovine free Cu/Zn-SOD, 7000 units/kg). When HB-SOD was administered with heparin (500-2000 units/kg), edema was suppressed more markedly than by HB-SOD alone. In contrast, the suppressive action of SOD was decreased by heparin. HB-SOD also suppressed carrageenan paw edema in rats with an ED30 of 2500 units/kg which was also obtained by SOD. Heparin prolonged significantly the duration of HB-SOD suppression of edema. The inhibitory effect of HB-SOD alone disappeared within 5 hr of injection, while more than 80% of the effect remained at this time when HB-SOD has been injected with 1000 units/kg of heparin. Heparin failed to enhance the anti-inflammatory effect of SOD under any of the conditions tested and heparin alone showed no suppression up to 5 hr after injection. HB-SOD might permit studies on pathophysiological events in and around vascular endothelial cells where reactive oxygen species play critical roles. PMID- 1872906 TI - The association of lipoprotein and hepatic lipase activities with high density lipoprotein subclass levels in men with myocardial infarction at a young age. AB - The relations between postheparin plasma lipase activities and concentrations of lipoproteins, in particular plasma high density lipoprotein (HDL) subclasses determined by gradient gel electrophoresis, were examined in 39 men who had survived a first myocardial infarction before the age of 45 years and in 20 age matched control men. Reduced lipoprotein lipase (LPL) and hepatic lipase (HL) activities were found in the patients due to low LPL activity in patients with hypertriglyceridaemia, and low HL activity in those with a normal lipoprotein pattern or hypercholesterolaemia. Considerably lower plasma HDL2b and HDL2a protein concentrations and higher plasma HDL3b and HDL3c protein levels were found in the patients compared with the healthy control subjects. The subgroup of patients with hypertriglyceridaemia accounted for the major proportion of the case control differences for the HDL subspecies. However, significantly lower HDL2b and HDL2a concentrations were seen also among the normotriglyceridaemic patients. Analysis of the correlations between concentrations of HDL subclasses and lipase activities revealed positive associations between LPL and HDL2b and negative associations between HL and HDL2b. For LPL, this relationship was confined to hypertriglyceridaemic and for HL to normotriglyceridaemic subjects. HL was indicated to be positively connected with HDL3b levels, irrespective of lipoprotein pattern, whereas LPL seemed to be unassociated with HDL3b. It is concluded that low LPL and HL activities partly account for the change in HDL subclass distribution observed in patients with myocardial infarction at a young age. PMID- 1872908 TI - Arterial lipid biochemistry in the spontaneously hyperlipidemic Zucker rat and its similarity to early atherogenesis. AB - In the present studies, arterial lipid metabolism was evaluated in the spontaneously hyperlipidemic obese Zucker rat (fa/fa), the lean Zucker rat (Fa/ ), and the Sprague-Dawley (SD) rat. Mean serum cholesterol levels in the obese Zucker, lean Zucker and SD rats were 216 +/- 18 mg/dl, 145 +/- 14 mg/dl and 84 +/ 5 mg/dl, respectively. Arterial cholesterol content was in the same rank order as plasma cholesterol and ranged from a mean of 2.23 +/- 0.10 mg/gm wet wt. in the obese rats to 1.36 +/- 0.04 mg/gm wet wt. in the SD rats. The increased arterial sterol in the obese rats was associated with increased lipid metabolism activity. The in vitro incorporation of [14C]oleate into arterial cholesteryl esters was increased 3-4-fold (P less than 0.01) and incorporation into phospholipids and triglycerides was also elevated (P less than 0.001 and P less than 0.01, respectively). The arterial sterol content and arterial lipid metabolism pattern observed in obese Zucker rat aortas are similar to those found in vessels of other species undergoing atherogenic change. PMID- 1872907 TI - Active cholesterol biosynthesis in cultured aortic smooth muscle cells: evolution during the life-span of the culture. AB - Cultured aortic smooth muscle cells from rabbit, in synthetic and contractile state, are considered good models for studying pathological and normal cells, respectively, during the atherosclerotic process. Cholesterogenic activity was compared in cells which were obtained in both states of the same subculture and incubated with labeled sodium acetate. This activity (expressed as the percentage of total cell radioactivity uptake transformed into cholesterol) was very high in synthetic cells and comparable to that of cancer cells. Cholesterol synthesis was lower in contractile cells and similar to that observed in a nonpathological cultured cell. During the cell life-span (studied in two cultures) cholesterogenic activity initially increased and then slowly decreased, in the two phenotypic states. Near the end of the culture life, cholesterol production drastically decreased, but this was due to a blocking of the last steps, lanosterol demethylation and C27 sterol transformation into cholesterol, rather than to a sharp decrease in the first steps of the cholesterogenic process. Cells in the synthetic and contractile states released newly synthesized lipids which were essentially late precursors of cholesterol, but accumulation of oxy-sterols was not observed. The excretion of metabolites increased with culture aging. PMID- 1872909 TI - Magnitude of dietary effects on plasma cholesterol concentration: role of sex and apolipoprotein E phenotype. AB - The effects of fat-controlled, low-cholesterol and high-fat, high-cholesterol diets pursued for 4 weeks on plasma lipids and lipoproteins were studied in 44 healthy middle-aged subjects (22 women and 22 men). All the calories were supplied from the hospital kitchen. When the subjects were switched from the fat controlled, low-cholesterol diet to the high-fat, high-cholesterol diet the average increase in total cholesterol was 1.2 mmol/l (28%), ranging from 0.2 to 2.7 mmol/l (4-56%). At the same time the average increase in LDL cholesterol was 1.0 mmol/l (39%), ranging from 0.1 to 2.4 mmol/l (3-90%). Interestingly, the men responded to the dietary changes more sensitively than the women. The increase in total cholesterol from the low-fat to the high-fat diet was 31% for the men and 25% for the women (P less than 0.05), the corresponding increases in LDL cholesterol being 42% and 37%, respectively (P less than 0.05). A marked increase in HDL cholesterol was observed when the subjects were switched from the low-fat to the high-fat diet, the increase being 30% for the men and 20% for the women. The absolute and percentage lipid changes on the two diets were equal in the subjects with the common apolipoprotein E phenotype 3/3 and in those homozygous and heterozygous for the epsilon 4 allele (E4/4 and E4/3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1872910 TI - Desialylated low density lipoprotein--naturally occurring modified lipoprotein with atherogenic potency. AB - We have recently established that low density lipoprotein (LDL) of most patients with coronary atherosclerosis differs from the LDL of most healthy subjects by its ability to cause primary atherosclerotic changes, i.e. the accumulation of intracellular cholesterol in the cells of smooth muscle origin cultured from unaffected intima of human aorta. Patients' LDL has a 2.5-5-fold lower content of sialic acid as compared with the LDL of healthy subjects. On the other hand, desialylation of native LDL with neuraminidase makes it capable of causing accumulation of intracellular cholesterol similar to patients' LDL. In the present study we showed that LDL of patients and healthy donors did not differ in the content and composition of protein and lipids. Thus, the difference in the content of sialic acid is the only difference observed between atherogenic LDL of patients and nonatherogenic LDL of healthy donors. A low content of sialic acid is characteristic of both protein and lipid moiety of LDL particle. Sialic acid content was determined in individual LDL preparations obtained from patients and healthy donors. The sialic acid of LDL preparations of 25 out of 27 patients was below 18 micrograms/mg protein. LDL from 2 patients with higher sialic acid content proved to be normal. The ability of patients' LDL and LDL desialylated with neuraminidase in vitro to cause the accumulation of intracellular lipids correlated with the degree of lipoprotein desialylation. Apparently, the ability of patients' LDL to stimulate the cellular lipid accumulation may be explained by a deficiency of sialic acid in the lipoprotein particle. PMID- 1872911 TI - Plasma factor VII is activated by postprandial triglyceridaemia, irrespective of dietary fat composition. AB - Nine adults took two 7-day diets of standardised energy and total fat content, but with a dietary polyunsaturated/saturated fat ratio of less than 0.3 and greater than 3.0 respectively, while adhering to their daily routine. Blood was drawn on 6 occasions between 09.00 and 22.45 h on the final day of each dietary period for factor VII activity (VIIc), factor VII antigen (VIIag) and lipoprotein lipid concentrations. Diurnal variation was described for each variable in terms of its deviation from the individual's daily mean value at each time point across the day. Plasma triglyceride remained low until after the midday meal, whereafter a marked rise was sustained into the later evening. Plasma VIIc declined until early afternoon, but showed a marked rise in the late afternoon. Plasma VIIag showed no significant diurnal variation. Changes in plasma triglyceride concentration during the day were related positively to changes in VIIc about 160 min later, but not to VIIc at other time points. This effect of postprandial triglyceridaemia on VIIc persisted after allowance for the effect of VIIag on VIIc. Dietary fat composition did not influence VIIc or VIIag. The results suggested an acute but evanescent effect of triglyceride-rich lipoproteins on the reactivity of factor VII, irrespective of their lipid core composition. PMID- 1872912 TI - Effect of simvastatin treatment on the dyslipoproteinemia in CAPD patients. AB - HMG-CoA reductase inhibitors have been proven effective in decreasing the plasma cholesterol levels in patients affected with various forms of hypercholesterolemia, familial dysbetalipoproteinemia, familial combined hyperlipidemia and in nephrotic and diabetic dyslipidemia. The purpose of this study was to monitor and evaluate the efficiency and safety of the therapy with simvastatin, an HMG-CoA reductase inhibitor, in a group of patients treated by continuous ambulatory peritoneal dialysis (CAPD) with severe hypercholesterolemia. Monitoring of the changes occurring in the various lipids and apolipoproteins in these patients included the measurements of the plasma lipids and apolipoproteins A-I, A-II, B, C-II, A-IV and Lp(a). Lipoproteins were separated by gel filtration, on a Superose 6HR column, before and after 24 weeks of treatment. The patterns were compared to those observed in a group of primary hyperlipidemic patients treated with Lovastatin, a compound of the same class. The drug was well tolerated by the CAPD patients and no adverse reaction was observed. In addition to the decrease of the total and LDL cholesterol, similar to that reported in other groups of patients, we further observed a decrease of the apo E concentration in both the CAPD and the hyperlipidemic patients. This decrease was especially pronounced in the HDLE fraction and could involve an upregulation of the apo B-E and/or apo E receptor. These results should provide information about the mechanism of action of this drug in patients with end-stage renal disease. PMID- 1872913 TI - Failure to detect homocysteine in the acid-hydrolysed plasmas of recent myocardial infarct patients. AB - We have sought the very high levels of homocysteine-containing compounds in the plasma hydrolysates of myocardial infarct patients reported by Olszewski and Szostak (Atherosclerosis, 69 (1988) 109-113). We studied 6 adult males with recent myocardial infarcts and 6 healthy adult males. We found that after hydrolysis of their plasmas for 5 h in 4 mol/l HCl at 110 degrees C, the amino acid chromatographs contained several small peaks in addition to the expected substantial peaks of the protein-constituent amino acids. However, the small peaks which eluted at the same times as homocysteine, homocystine and the mixed disulphide of homocysteine and cysteine, were in each case shown not to represent these compounds. Furthermore no homocysteine thiolactone was found in the chromatographs. We found no significant differences in the size of the small peaks between the patients and the controls. Prolonged hydrolysis resulted in decreased size of all but one of the small peaks suggesting that they were hydrolytic intermediates in the breakdown of plasma proteins. Electrophoresis at pH 10.39 of the unhydrolysed plasmas showed that the proteins were not significantly more homocysteinylated in patients than in controls. Thus we have been unable to substantiate some key observations made by Olszewski and Szostak. PMID- 1872914 TI - Psychosocial and biobehavioral characteristics of hypertensive men with elevated atherogenic lipids. AB - Epidemiologic studies demonstrated an excess risk of ischemic heart disease (IHD) among individuals who simultaneously exhibit hypertension and elevated atherogenic lipids (coronary high risk (CHR)-status). Yet, relatively little is known about factors which contribute to the development of CHR-status during early and middle adulthood. The present study explores the role of selected biobehavioral and psychosocial factors in explaining CHR-status using data from a prospective 6.5 years investigation of a cohort of 416 middle-aged (40.8 +/- 9.6 years) male blue-collar workers. Multivariate logistic regression analysis shows that overweight (odds ratio (o.r.) 4.14), smoking (o.r. 2.19), low promotion prospects at work (o.r. 2.71), competitiveness at work (o.r. 2.79) and feelings of sustained anger (o.r. 5.41) independently contribute to the explanation of CHR status. Furthermore, the operational definition of CHR-status is validated by estimating its power in predicting IHD incidence in the study cohort. In conclusion, co-manifestation of hypertension and elevated lipids is more likely to exist among those blue-collar men who exhibit distinct work-related characteristics in addition to established biobehavioral risks such as overweight and smoking. In view of the high prevalence of CHR-status and of IHD among men in the lower socio-economic strata this finding is also of interest for health policy. PMID- 1872915 TI - Secretion of a potent new migration factor for smooth muscle cells (SMC) by cultured SMC. AB - Migration of smooth muscle cells (SMC) in the arterial wall is important in the formation of intimal thickening. In this work, cultured SMC from the rat and rabbit aortic media at 2nd to 12th passages were found to secrete a potent migration factor for SMC which was named SMC-derived migration factor (SDMF). This factor stimulated the migration of SMC dose-dependently and its maximum activity was 2-8 times that of PDGF. Checker board analysis showed that SDMF was chemotactic, but not chemokinetic. In further studies, SDMF was found to be inactivated at 100 degrees C for 10 min or by trypsinization, but not inactivated by mercaptoethanol. This factor was not dialyzable. Molecular weight was approximately 500 kDa by a gel filtration. The activity was not inhibited by an anti-PDGF antibody or a fibronectin antiserum. These data suggest that SDMF is a potent migration factor for SMC and that SDMF is distinct from PDGF, fibronectin or other known migration factors. This autocrine system of secretion of SDMF by SMC and its induction of SMC migration may contribute to intimal thickening of the arterial wall in atherosclerosis. PMID- 1872916 TI - A standardised method of culturing aortic explants, suitable for the study of factors affecting the phenotypic modulation, migration and proliferation of aortic smooth muscle cells. AB - The study of factors affecting phenotypic change and growth of aortic smooth muscle cells (SMC) typically involves either the isolation of SMC by enzymatic dissociation or observation of outgrowth of cells from primary explants of vascular tissue. Explants provide a system in which the growth of cells can be investigated without dissociating them totally from their normal environment and avoids some of the problems of variability associated with enzymatic digestion. We describe here a standardised method for the preparation of medial explants of arterial tissue using a McIlwain tissue chopper, which is both fast and reproducible. Measurement was made of the percentage of explants showing outgrowth and of the distance migrated by cells at various times after plating explants singly into wells of a 96-well plate. Using this method, by 12 days after explanting, more than 95% of explants from normal rabbit aorta had shown outgrowth, in contrast to only 50% of explants prepared using a scalpel blade. Explants from atherosclerotic rabbit aorta showed a shorter lag phase before outgrowth commenced than explants from normal rabbit aorta of a similar age, but the subsequent rate of growth was the same. In contrast, when explants of normal rabbit aorta were grown in hyperlipidic rabbit serum, the lag phase was the same as for normal serum, but the subsequent rate of growth was greater. Explants from normal rabbit aorta treated with heparin showed an increased lag phase but reduced rate of growth. Treatment with heparinase decreased the lag phase and increased the rate of growth as did elastase. PMID- 1872917 TI - Molecular basis of lipoprotein lipase deficiency in two Austrian families with type I hyperlipoproteinemia. AB - To determine the molecular basis for type I hyperlipoproteinemia in two Austrian families, the lipoprotein lipase (LPL) gene of two patients exhibiting LPL deficiency was analyzed by Southern blotting and by direct genomic sequencing of DNA amplified by polymerase chain reaction (PCR). All exons of the LPL gene except part of the noncoding region of exon 10, all splice donor and acceptor sites, as well as 430 basepairs of the 5'-region including the promotor were sequenced. A homozygous substitution of adenine for guanine in the fifth exon at cDNA position 818 of the LPL gene was found in both patients. Our sequencing strategy largely ruled out a linkage disequilibrium of the identified nucleotide change with another defect potentially causing the clinical phenotype. The base change described abolishes a normally present AvaII restriction site allowing the identification of carriers of the mutant allele by AvaII digestion of PCR fragments of exon 5; three members of the two families were homozygous for this mutation and ten members were heterozygous. The activity of LPL in postheparin plasma was almost completely absent in homozygotes and about half normal in heterozygotes. The loss of activity was related to LPL protein structure. This mutation alters the amino acid sequence at residue 188 from Gly to Glu. The conformational preferences of the protein chain around position 188 were calculated with the use of a knowledge-based computerized method. The most probable conformation is a beta-turn formed by residues 189-192. The mutation seems to destabilize the beta-turn and/or a yet larger domain critical for substrate alignment. PMID- 1872918 TI - Body fat distribution in relation to serum lipids and blood pressure in 38-year old European men: the European fat distribution study. AB - A study on 512 38-year-old European men selected from 6 different towns was conducted. There were significant differences between the centers in averages of anthropometric variables (except for thigh circumference), serum lipids (except for LDL-cholesterol), and blood pressure. In the pooled material, body mass index (BMI) as well as waist circumference, waist/hip ratio and waist/thigh ratio and subscapular skinfold were positively correlated to serum triglycerides, total cholesterol, LDL-cholesterol, and blood pressure and negatively with HDL cholesterol. After adjustment for BMI, waist, waist/hip, and waist/thigh were all still significantly correlated with serum triglycerides (P less than 0.001). In addition, waist/hip and waist/thigh ratio showed significant partial correlations with total cholesterol (r = 0.16, P less than 0.001, r = 0.10, P less than 0.05 respectively), and diastolic blood pressure (r = 0.10, P less than 0.05, r = 0.09, P less than 0.05 respectively). In addition, waist/hip was, independently of BMI, correlated to LDL-cholesterol (r = 0.12, P less than 0.01), and waist/thigh ratio with HDL-cholesterol (r = -0.12, P less than 0.01). The partial association between waist/thigh with HDL cholesterol became insignificant after adjustment for smoking habits and physical activity. Adjustment for differences in anthropometric measurements did not explain the differences in serum lipids and blood pressure between the centers. The authors conclude that indicators of body fat distribution are associated with unfavorable risk profiles for cardiovascular disease in European men covering a large geographical and cultural variety and a wide range of body measurements and cardiovascular risk factors. PMID- 1872919 TI - Inhibition of IL-1 beta expression in THP-1 cells by probucol and tocopherol. AB - The cytokine interleukin-1, IL-1, likely plays an important role in the early stages of atherogenesis. The possible action of probucol and tocopherol on the expression and secretion of IL-1 beta was investigated using the human monocytic leukemia cell line, THP-1. Both probucol and D-alpha-tocopherol inhibit the phorbol ester-induced release of IL-1 beta without altering differentiation. Analysis of IL-1 beta mRNA levels revealed that probucol and tocopherol had an inhibitory effect on the activation of expression of the IL-1 beta gene. The data suggest that the beneficial effects of probucol may be related to inhibition of IL-1 at an early phase of atherosclerotic plaque formation. PMID- 1872920 TI - Dietary fat and hormonal influences on lipoprotein fluidity and composition in premenopausal women. AB - LDL and HDL became more fluid when health, free-living, premenopausal women were fed reduced fat diets with higher proportions of polyunsaturated fatty acids. Lipoproteins were isolated from plasma of 31 female subjects fed one of two sets of diets from typical U.S.A. foods with P/S ratios of 0.3 or 1.0. All subjects were fed high-fat diets (40% of energy) for the duration of four menstrual cycles followed by low-fat diets (20% of energy) for the next four cycles. Blood samples were collected during mid-follicular and mid-luteal phases of the fourth menstrual cycle of each diet period to assess interactive dietary and hormonal control of lipoprotein fluidity. LDL was significantly more fluid, as determined by DPH fluorescence, upon reducing fat consumption from 40 to 20% of energy for subjects eating foods with P/S = 1.0 or 0.3. Generally LDL was more fluid during the follicular phase than the luteal phase of the cycles, thus indicating hormonal influences on LDL fluidity. HDL results were similar but not as pronounced as with LDL. Lipoprotein phospholipid (PL) and cholesteryl ester (CE) fatty acyl compositions were also subject to dietary and hormonal influences. Effects were noted in several fatty acids depending upon diet and hormonal state; however, generally diet fat reduction resulted in reduced linoleate and increased oleate contents. Regression analyses showed that fluidity was more dependent upon the lipoprotein cholesterol content than upon fatty acyl composition. PMID- 1872921 TI - Lifestyle determinants of HDL2- and HDL3-cholesterol levels in a hypercholesterolemic male population. AB - In this cross-sectional study we investigated the role of lifestyle and other factors in determining serum HDL2- and HDL3-cholesterol levels among 82 dyslipidemic (total cholesterol minus HDL-cholesterol greater than or equal to 5.2 mmol/l) middle-aged participants of the Helsinki Heart Study. Alcohol consumption correlated positively with both subfractions of HDL-cholesterol, while leisure time physical activity had a significant correlation with the HDL3 subfraction only. HDL levels were lower in smokers than in non-smokers but the differences were not statistically significant. Using the multiple linear regression model, alcohol consumption emerged as the only significant factor influencing both HDL cholesterol subfraction levels. Leisure time physical activity had an independent contribution to HDL3-level, but lifestyle variables other than alcohol consumption did not contribute significantly to HDL2 cholesterol level. The model incorporating alcohol consumption, physical activity, smoking and relative body weight explained 13.4% of the variation in HDL2 and 17.5% in HDL3-cholesterol. PMID- 1872922 TI - Serum lipids and apolipoproteins in patients with essential hypertension. AB - Fifty hypertensive untreated outpatients (34 women, 16 men), with stage I and II essential hypertension, were studied in comparison to 50 age- and sex-matched controls with similar life-styles. Total cholesterol triglycerides, LDL cholesterol, VLDL-cholesterol, and HDL-cholesterol were measured by enzymatic methods, and apolipoproteins AI, AII, B, CII, CIII and E by RID. The results showed significant differences between hypertensives and controls respectively in triglycerides (135.2 +/- 73.9 versus 90.2 +/- 33.8, P less than 0.01) and VLDL cholesterol (26.7 +/- 14.8 versus 17.7 +/- 6.6, P less than 0.01) while no significant differences were observed in total, LDL and HDL cholesterol. Significant differences between the two groups were also observed in apolipoproteins, particularly in apo AI (130.0 +/- 28.2 versus 144.9 +/- 27.9, P less than 0.05), apo AII (32.9 +/- 10.2 versus 39.6 +/- 11.4, P less than 0.01), apo CII (4.0 +/- 2.6 versus 5.4 +/- 2.9, P less than 0.05) and apo E (5.0 +/- 1.8 versus 4.3 +/- 1.8, P less than 0.05), while no significant differences were observed in apo B and CIII values. The results suggest that in untreated hypertensive patients alterations in the apolipoproteins profile are present which, in part, may be responsible for the elevated incidence of cardiovascular disease, independently from the blood pressure values. PMID- 1872923 TI - Intermediate density lipoprotein levels are strong predictors of the extent of aortic atherosclerosis in the St. Thomas's Hospital rabbit strain. AB - This study assessed nonfasting cholesterol and triglyceride in plasma and in lipoproteins as predictors of the extent of aortic atherosclerosis in 2 similar groups of rabbits from the St. Thomas's Hospital strain; the lipoprotein classes studied in the 2 groups were very low (VLDL), intermediate (IDL), low (LDL), and high density lipoprotein (HDL), and Sf greater than 60 lipoprotein, Sf 12-60 lipoprotein, LDL and HDL, respectively. These rabbits exhibit elevated plasma levels of VLDL, IDL, and LDL, with plasma cholesterol and triglyceride of up to 23 mmol/l and 7 mmol/l, respectively, and with up to 100% of the aortic intima bearing atherosclerosis-like lesions. In group 1 rabbits (n = 25), univariate linear regression showed that cholesterol in plasma, LDL, IDL and in VLDL each were positively associated with the extent of aortic atherosclerosis. In group 2 rabbits (n = 20), cholesterol in plasma, LDL and Sf 12-60, but not in Sf greater than 60 lipoprotein, was consistently positively associated with the extent of aortic atherosclerosis. Neither plasma triglyceride, triglyceride in lipoprotein fractions nor HDL cholesterol was associated consistently with the extent of atherosclerosis. Using step-up multiple linear regression among lipoprotein lipids, IDL and Sf 12-60 lipoprotein cholesterol were the most powerful independent predictors of the extent of aortic atherosclerosis in the 2 groups of rabbits. LDL cholesterol was the only other independent predictor. The results suggest that remnant lipoproteins, whether defined as IDL or Sf 12-60 lipoprotein, play an important causal role in atherosclerosis under conditions where plasma levels of these lipoproteins are elevated. PMID- 1872924 TI - Effect of cigarette smoking on the levels of platelet-activating factor-like lipid(s) in plasma lipoproteins. AB - The effect of cigarette smoking on the levels of platelet-activating factor-like lipid(s) (PAF-LL) in plasma lipoproteins was studied. The subjects were 10 healthy male non-smokers (24 +/- 1.4 years old) and 13 healthy male habitual smokers (23 +/- 1.3 years old). Fasting venous blood was obtained and basal levels of PAF-LL in plasma lipoproteins were estimated. The acute effect of cigarette smoking was also studied in smokers. Plasma lipoproteins were separated by ultracentrifugation. Lipids were extracted and separated by thin-layer chromatography. The fraction with the same migration as authentic PAF was recovered and was shown to cause aggregation of human polymorphonuclear neutrophils. This activity was identified as PAF-LL because it was inactivated by phospholipase A2 and was blocked by CV-3988, an antagonist of the PAF receptor. PAF-LL was detected in LDL and HDL, but not in VLDL or in lipoprotein-deficient plasma. The levels of PAF-LL in LDL in non-smokers, and in smokers before and after smoking were 13 +/- 7.5, 16 +/- 14.9 and 190 +/- 179.0 pg/ml, and those in HDL were 12 +/- 5.2, 40 +/- 40.0 and 235 +/- 205.1 pg/ml, respectively. The values in both LDL and HDL in smokers increased significantly after smoking (P less than 0.05). After 30 min, the levels had returned almost to the pre-smoking levels. We conclude that cigarette smoking induces an increase in the levels of PAF or closely related lipid(s) in LDL and HDL, which may be related to smoking induced atherosclerosis. PMID- 1872925 TI - A controlled study on the effects of n-3 fatty acids on lipid and glucose metabolism in non-insulin-dependent diabetic patients. AB - Eight male non-insulin-dependent diabetic patients participated in a double-blind randomized cross-over study (2 weeks for each period) evaluating the effects of 10 g/day fish oil dietary supplementation on glucose and lipid metabolism. Fasting serum triglyceride concentrations were decreased by fish oil because of a reduction in VLDL (1.4 +/- 0.2 vs. 1.9 +/- 0.2 mmol/l, P less than 0.025). LDL cholesterol concentration was instead increased (3.4 +/- 0.3 vs. 2.8 +/- 0.3 mmol/l, P less than 0.025) and net changes in VLDL triglyceride and in LDL cholesterol were inversely correlated (r = -0.86, P less than 0.01). Plasma free fatty acids concentrations and turnover rate [( 3H]palmitate method) were similar after fish oil and placebo. Fish oil supplement did not induce significant changes in fasting blood glucose (8.1 +/- 1.1 vs. 8.5 +/- 1.2 mmol/l) and average daily blood glucose (BG) (9.4 +/- 3.2 vs. 9.3 +/- 3.5 mmol/l). Glucose stimulated plasma insulin response during a hyperglycemic clamp was not significantly influenced by fish oil both in the early phase and during steady state. Insulin sensitivity (M/I index) was also unchanged. In conclusion, this study shows that a dietary supplement of fish oil decreases plasma triglyceride levels in non insulin-dependent diabetic patients, an increased conversion rate of VLDL to LDL playing a role in this change. With this dosage of fish oil no relevant variations in glycemic control, insulin secretion and insulin sensitivity occurred. PMID- 1872927 TI - Home infusion pumps. PMID- 1872926 TI - Atherosclerotic plaque caps are locally weakened when macrophages density is increased. AB - The density of macrophages, identified by the antibody EBMII, in human aortic plaque caps was counted. A contiguous strip of cap tissue was tested mechanically. Aortic plaque caps which had undergone rupture (ulceration) at one end (n = 18) were compared with caps of intact plaques (n = 22). The caps of ruptured plaques showed a significant increase in macrophage density, an increased extensibility and decreased maximum stress (force per unit area) at fracture when compared with caps from intact plaques. PMID- 1872928 TI - The great debates. Where, how, and what to teach deaf children. PMID- 1872929 TI - [Functional deficits of caudal cranial nerves after surgery of tumors in the foramen jugulare. A long-term follow-up study]. AB - Jugular foramen tumors involve a critical area of the skull base. Usually they are characterized by palsy of the ninth, tenth, and eleventh cranial nerves. Depending on the extent of the tumor there are various approaches to the skull base and various surgical strategies to preserve the cranial nerves. The study is based on 31 patients who were operated on between 1982 and 1989 at the University ENT and Neurosurgery Departments in Freiburg and Mainz. The neurological findings were analyzed on admission, on discharge, and in the follow-up. While there was partial or complete dysfunction of the lower cranial nerves on discharge, long term compensation was excellent. All patients were able to breath normally and maintain their weight by oral diet. Rerouting of the facial nerve endangers its postoperative function. Nevertheless, the long-term follow-up demonstrated excellent recovery and good functional and cosmetic results. PMID- 1872930 TI - [Computerized tomography as routine examination procedure in the diagnosis of paranasal sinus diseases from the otorhinolaryngologist's viewpoint. Results]. AB - The renaissance of endonasal microsurgery is not only based on a deeper knowledge of the mucociliar clearance and better operation instruments but depends as well as on the improved radiological diagnosis provided by computed tomography. Since 1986, high-resolution computed tomography in two plains has been part of the authors' preoperative routine diagnostic program for paranasal sinus diseases at their clinic. One hundred and fifty-eight computed tomograms of patients with chronic rhinosinusitis, complicated acute rhinosinusitis, and polyposis nasi were reexamined. The involvement of the paranasal sinuses and abnormalities of the lateral nasal wall were analyzed. The anterior ethmoid is the most frequently affected area in all of the diseases. The computed tomogram is most important for the rhinosurgeon. The ethmoid cell system can be visualized without superimposing structures. Therefore even circumscript pathologic mucosa alterations and the extent of the disease can be defined. All this enables the surgeon to put forward an exact diagnosis and to plan a safe operation as regards important physiological structures of the nose and paranasal sinuses. PMID- 1872931 TI - [Diagnostic approach in diseases of the parapharyngeal space]. AB - Diseases of the parapharyngeal space (p.s.) are quite rare. Nevertheless, the clinical and therapeutic approach to this anatomical site is not easy in many cases. Possibly some of the patients suffering from lesions in the p.s. could be cured, if the disease were detected in an earlier stage. In the present paper the authors introduce the diagnostic evaluation of this region. Clinical and radiological procedures are demonstrated in selected patients with characteristic lesions of the p.s. in order to find out about reasonable and sufficient diagnostic approaches to this hidden area. While the clinical examination is limited mainly to inspection and palpation, diagnostic imaging--and particularly modern techniques like CT, MRI and 3-D-reconstruction--enables us to receive a better approach to the p.s.. Advantages and disadvantages of the different methods are discussed according to their diagnostic value for the various kinds of lesions in the p.s. PMID- 1872932 TI - [Malignant melanoma of the mucous membranes of the upper aerodigestive tract. Clinical, histological and immunohistochemical characteristics]. AB - Malignant melanomas of the mucous membranes are rare tumors. They make up about 10% of all malignant melanomas of the head and neck; 15 of the authors' cases are reviewed in this article. Six of these had neck lymph node metastasis when first diagnosed. The tumors were surgically removed in all patients. Thirteen patients developed at least one tumor recurrence, ten patients distant metastasis. Eight patients died of the tumor condition; the mean survival time of all patients was 33.4 months. While the tumors could be classified histologically into four types, this had no bearing on the course of the disease. In many cases, primary tumor and metastasis or recurrent tumor differed histologically. Melanin pigment was found in 13 tumors. Mucosal melanomas can be regarded as a discrete tumor entity because their biological behavior differs from that of malignant melanomas of the skin. However there are no morphological differences between the two tumor entities. Ophthalmological and dermatological examinations must be performed in all patients with mucosal melanoma to exclude metastasis of the skin or choroid melanoma. PMID- 1872933 TI - [Treatment results after supraglottic partial resection of the larynx in carcinoma of the laryngeal entrance, the base of the tongue and hypopharynx. 2. Radiotherapy and late results after combined surgical-radiological treatment]. AB - 110 Patients were followed-up after supraglottic laryngectomy: The 3-year survival rate was 74%. The overall 5-year survival rate was 49%. For the cases of T3-tumours from these of the entrance of the larynx the 5-year survival rate was about 73%. For the T4-tumours the 5-year survival rate was only about 22%. Better results are not possible at the present even if other kinds of therapy are used. PMID- 1872934 TI - [Drug therapy of progressive hearing disorders in children]. AB - In 1987 and 1988 Nickisch et al. discussed the effect of infusions of prednisolone, pentoxifylline and, partially, piracetam in Ringer lactate solvent on progressive sensorineural hearing loss in childhood and adolescence. Time of observations was 4 years. Unfortunately long-term investigations could not confirm the initially good therapeutic results of 1987/88. In 35% were found permanently and in 12.5% temporarily better auditory thresholds after infusion. The loss of progressive sensorineural hearing in childhood usually takes a fateful course that can hardly be influenced. As is the case with adults, good therapeutic results can most probably be achieved by infusions starting close to the event, i.e. within 48 hours. PMID- 1872935 TI - [Hearing ability after dissection of the vertebral nerve. A long-term study]. AB - To prove the influence of the vertebral nerve on hearing in rabbits, the vertebral artery, together with its sympathetic plexus (n. vertebralis Frank), was unilaterally cut at the height of the first vertebral body, the atlas. Both preoperatively and several times after dissection, auditory and vestibular functions were investigated using BERA and electronystagmography. The hearing threshold was not influenced, neither in the first days after the operation nor as much as six months later. The latencies between wave I and V did not change. Similar results were to be found for the vestibular system. There was no imbalance clinically and it was not possible to detect any electronystagmographic difference between the two vestibular organs. These results indicate, that there is still no experimental proof of hearing loss, as a result of disturbance of the sympathetic vertebral nerve. PMID- 1872936 TI - [Cervical tinnitus after cervical vertebrae treatment]. AB - There is a wide variety in the discussions on cervical tinnitus as a possibility of hearing disorders. Hearing loss at low frequencies and low frequent tinnitus are typical signs in this context. It is important to remember that these complaints occur not only with pathological changes in the cervical spine, but possibly also after treatment in this region. The patients presented here suffered from tinnitus or hearing loss after treatment of the cervical region. In all cases the cervical spine is clearly indicated as having triggered the signs. When diagnosing and treating patients with complaints of the cervical area, there should be close cooperation between the physician, the patient and the physiotherapist. PMID- 1872937 TI - [Course of early vestibular compensation after acute labyrinthine lesions. A clinical-experimental longitudinal study]. AB - This study discusses early vestibular compensation in man. Fifty-five patients suffering from acute vestibular lesions were clinically followed up over six months. More than 450 examinations were carried out, using several subtests such as observation of spontaneous, position, and positional nystagmus with Frenzel's glasses, and registrations of pendular rotation test and bilateral bithermal calories using electrooculography. The results were calculated and recorded on graphs to permit estimation of the influence of vestibular compensation on the features examined. In 71%, i.e., in 39 of the 55 patients, the side of hypoexcitability, the direction of spontaneous nystagmus, direction of preponderance, and deviation in Unterberger's stepping test changed from left to right and vice versa during compensation. It was not possible to discover a homogeneous time-course of compensation. The results have to be considered with respect to the evaluation of vestibular findings, especially in preoperative examinations to locate vestibular disturbances. The article proposes a graduated time schedule for follow-up examinations. PMID- 1872938 TI - [Pseudotumor of the hypopharynx and other primary diseases in the head and neck region in HIV infections. A case report and review of the literature]. AB - The present article describes a pseudotumor of the hypopharynx, and deteriorating breathing and swallowing in a 72-year-old man. The pseudotumor was due to advanced HIV-infection and is the first such case to be described. Additionally, the article reviews the literature concerning otorhinolaryngeal diseases as primary manifestations of HIV infection. PMID- 1872939 TI - [Comparative studies of the filtration behavior of bacteria and organic particles in porous ground water pipes. II. Hydraulic, hydrochemical and sedimentation system properties which control the filter factor]. PMID- 1872940 TI - [Effect of the reflection of UV rays in the disinfection of drinking water]. AB - The disinfection of drinking water by means of UV-rays represents an interesting alternative to chemical disinfection. However, several questions still remain to be answered, making the disinfection of drinking water by means of UV-radiation appear unsafe. The regulations concerning the disinfection performance of UV systems are still presenting difficulties. Within the course of comparative experiments in the laboratory and using a flow-through reactor on the disinfection effectiveness of UV-radiation, it has been shown that the reflection of UV-rays can have a considerable influence on the disinfection effectiveness. In order to be able to make reliable statements on the dose-effect relation it is necessary, therefore, to record exactly the radiation applied, including the reflected proportion. PMID- 1872941 TI - [Seroepidemiologic studies of human toxocariasis]. AB - People of Southern Germany as well as European and non European asylum applicants were examined for Toxocara-infection by means of an ELISA with excretory/secretory antigen of Toxocara canis-larvae; in default of a reference method the cut off was defined statistically. In the Stuttgart area, the average seroprevalence of healthy blood donors was 4.8%; children aged 1-7 years showed a seroprevalence of 2.1%. However the low percentage in children sera is probably not the effect of a lower risk of infection, but may result from the fact that most of the tested children live in city areas. Non-Europeans and Eastern Europeans showed a significantly higher seroprevalence (13.7% or 17.7% respectively) in comparison to the blood donors from Southern Germany. This indicates a higher risk of infection in these countries. It was possible to determine the different risk factors for a Toxocara canis-infection with some of the test-participants in Southern Germany. Compared to the low-risk-group (seroprevalence 1.9%), the test groups with risk factors showed a significant increase in seroprevalence: dog-owners 5.6%, owners of domestic cattle 9.4%, cat owners 10.9%, farmers 22.6%. In the presence of several risk factors an additive effect on the seroprevalence could be found: In the test group with one risk factor the seroprevalence (9.2%) was lower than in the test groups with two (10.8%) or three risk factors (18.6%). Considering the high prevalences found in this study and the possible dangerous complications of Toxocara canis-infections, medical and hygienic measures seem to be advisable. PMID- 1872942 TI - [Acanthamoeba, Naegleria and invertebrates in wet areas of physiotherapy equipment in hospitals]. AB - In the course of investigations on the occurrence of primary free-living amoebae in different aquatic habitats, especially Naegleria and Acanthamoeba, we now investigated the moist areas in physiotherapeutic departments of 10 hospitals. As a result 61% of the swabs taken in those areas were positive with one or several species of amoebae cultivated on NN-agar according to Page. Among many other species observed during this study we were able to isolate 47 strains of Acanthamoeba and only two strains of Naegleria. The Naegleria-strains did not appear to be thermophilic. Therefore they are part of the N. gruberi-complex, which is considered to include only non pathogenic strains. Six from 47 strains of Acanthamoebae isolated revealed pathogenic characters as demonstrated in the MIT (Mice inoculation test). As a remarkable result four of these 6 strains with proven pathogenicity were not thermophilic at + 40 degrees C. Eventually all strains even not being thermophilic should in future be tested on pathogenicity. Additionally, nematodes and rotifers were isolated from several samples. PMID- 1872943 TI - [MUG-lauryl sulfate bouillon--an optimal medium for the detection of total coliforms and fecal coliform bacteria in relation to hygienic evaluation of bathing waters according to the European Community Guideline 76/160 EWG]. AB - In the monitoring of bathing waters according to the EC-guideline, total coliform and faecal coliform bacteria were obtained from 97 samples of river waters by the comparison of two fluorogenic assays using MUG-Lauryl Sulfate Broth and MUG-BRILA Broth with an usual method with MacConkey Broth, Tryptophane Broth and BRILA Broth. MUG-BRILA Broth had the lowest average counts and proved to be not an appropriate medium. Compared with the usual method, however, MUG-Lauryl Sulfate Broth yielded similar high counts, reduced the investigation period from four to two days and diminished the expenditure of work by one third. In addition, the indole test for the confirmation of presumptive faecal coliforms might be abolished. Therefore, the examination with MUG-Lauryl Sulfate Broth can be recommended. PMID- 1872944 TI - [UV radiation of waste water from a purification plant for the improvement of bathing water quality according to European Community Guidelines]. AB - During the course of one year, 162 sewage samples were taken from the outlet of a sewage purification plant before and after u.v. - irradiation and examined for bathing water quality according to EC guidelines. Roughly half of the u.v. - irradiated samples were lower than the bathing water limit. PMID- 1872945 TI - Influence of aglycone modifications on the binding of anthracycline drugs to DNA: the molecular structure of idarubicin and 4-O-demethyl-11-deoxydoxorubicin complexed to d(CGATCG). AB - X-ray diffraction analyses of the complexes between two anthracycline antitumor compounds, idarubicin (IDR) and 4-O-demethyl-11-deoxydoxorubicin (ddDOX), with the DNA hexamer d(CGATCG) provided the detailed three-dimensional molecular structures at 1.7 A and 1.8 A resolution, respectively. Their structures have been refined with the constrained refinement procedure to final R-factors of 0.188 (1724 reflections for IDR) and 0.179 (1247 reflections for ddDOX). The overall structures of both complexes are similar to those of the previously studied DAU- and DOX-DNA complexes. In both complexes, two IDR (and ddDOX) molecules bind to the DNA hexamer double helix with the elongated aglycone chromophore intercalated between the CpG steps at both ends of the helix. The aglycone chromophore spans the GC Watson-Crick base pairs with its amino sugar lying in the minor groove where little structural difference is seen, compared with the daunorubicin-d(CGATCG) and doxorubicin-d(CGATCG) complexes. In contrast, the missing C4 methoxy of IDR and the missing methyl group at the O4 position of ddDOX result in a different binding surface in the major groove. The O4 hydroxyl group is capable of receiving and/or donating a hydrogen bond to proteins that bind to the drug-DNA complex. The missing O11 hydroxyl group in ring B creates an empty space in the intercalation cavity between the two GC base pairs, which appears to affect the stacking interactions between the aglycone and the DNA base pairs. Those structural changes in the major groove of the drug-DNA complexes due to the modifications of the aglycone chromophore may be responsible in part for the difference in their biological activities. PMID- 1872947 TI - Synthesis and anti-tumour activity of the spatially-separated mustard bis-N,N'-[3 (N-(2-chloroethyl)-N-ethyl)amino-5-[N,N-dimethylamino)methy l)-aminophenyl]-1,4 benzenedicarboxamide, which alkylates DNA exclusively at adenines in the minor groove. AB - The mustard derivative, bis-N,N'-[3-(N-(2-chloroethyl)-N-ethyl)amino-5- [N,N dimethylamino)methyl)aminophenyl]-1,4-benzenedicarboxamide has been synthesized from 3-acetamido-5-nitrobenzoic acid in a 6-step procedure. This compound alkylates exclusively in the minor groove of DNA, at the N3 site of adenines occurring in sequences of runs of adenines and (to a small extent) at 5'-TA and 5'-AT sites. Gel electrophoresis studies and in vitro cytotoxicity assays against repair-deficient AA8 mutant cell lines show it has a high degree of DNA interstrand cross-linking ability. PMID- 1872946 TI - Aziridinyl nitropyrroles and nitropyrazoles as hypoxia-selective cytotoxins and radiosensitizers. AB - A series of 1- and 2-substituted 4- and 5-nitropyrroles and 3- and 4 nitropyrazoles has been prepared and evaluated in vitro as radiosensitizers of hypoxic cells and as bioreductively-activated cytotoxins. Both the nitropyrroles and the nitropyrazoles were considerably less effective, based upon the differential between hypoxic and aerobic toxicity, than were similar 2 nitroimidazoles bearing alkylating moieties. The trends in radiosensitizing efficiency observed for both classes of drugs corresponded with their one electron reduction potentials (E1(7] as measured by pulse radiolysis, although they were generally more effective than predicted from previous correlations of E1(7] with sensitizing efficacy and reactivities. Furthermore, the enhancement of sensitizing efficiency by the incorporation of alkylating groups is considerably greater than has been observed for nitroimidazoles. alpha-[(1-Aziridinyl)methyl] 3-nitropyrazole- 1-ethanol (10, E1(7) = -456 mV) and methyl 5-nitro-1 (cyclopropylcarbonyl)pyrrole-2-carboxylate (25, E1(7) = -326 mV) were the most effective radiosensitizers in vitro. Only 3-[cis-2,3-dimethyl-1-aziridinyl) methyl)-1-oxo-3,4-dihydro-6-nitro-1-H-pyrrolo [2,1-c] oxazine (22) and methyl 5 nitro-1-(cyclopropylcarbonyl)pyrrole-2-carboxylate (25) showed significant bioreductively-activated cytotoxicity, with differentials of 3.5. Although these differential toxicities were coupled with significantly lower aerobic toxicity compared with similar 2-nitroimidazoles, this series was not deemed effective enough to warrant further evaluation. The electron affinity and radiosensitization could be manipulated by chemical design but hypoxia selectivity was not clearly related to these properties. PMID- 1872948 TI - Selective toxicity of 1-methyl-4-phenylpyridinium ion (MPP+) to pigmented melanoma cells in vitro. PMID- 1872949 TI - The genetic changes in cancer. PMID- 1872950 TI - Elevation of glucose transporter, c-myc, and transin RNA levels by Ha-rasT24 is independent of its effect on the cell cycle. AB - Elevation of the steady-state mRNA levels of glucose transporter and c-myc are among the earliest changes in gene expression observed after Ha-rasT24 stimulation of Rat-1 fibroblasts to enter the cell cycle. Since the expression of these genes may be the result of either increased cell proliferation or a specific response to rasT24, we evaluated the expression of glucose transporter and c-myc and their induction during the cell cycle in both parental Rat-1 cells and cell lines bearing a metallothionein rasT24 fusion gene (MTrasT24). We showed that, although levels of glucose transporter and c-myc mRNAs in Rat-1 cells underwent a transient increase within hours of the addition of serum, epidermal growth factor, or 12-O-tetradecanoylphorbol-13-acetate to quiescent (G0) cells, the levels of glucose transporter and c-myc mRNA otherwise remained constant throughout the normal cell cycle. In cells carrying MTrasT24 (MR5 cells), induction of rasT24 expression by ZnSO4 led to a rapid induction of glucose transporter and c-myc mRNA expression in both quiescent (density-arrested) and G1/S-synchronized (aphidicolin-blocked) cells. These increases exceeded the constitutive levels expressed in rapidly proliferating Rat-1 cells, indicating that the ras oncogene has an effect on these genes that is independent of growth status. In addition, the transin gene, which is not expressed in proliferating Rat-1 cells in the continuous presence of serum growth factors, was also induced after increased expression of the mutant ras gene. These results suggest that the induction of glucose transporter, c-myc, and transin is the direct result of rasT24-mediated alterations in cellular gene expression and is distinct from normal cell-cycle events. PMID- 1872952 TI - Eleventh annual meeting of the American Society for the Immunology of Reproduction. Charlottesville, Virginia, June 23-27, 1991. Abstracts. PMID- 1872951 TI - A monoclonal antibody to rat liver cytochrome P450 IIC11 strongly and regiospecifically inhibits constitutive benzo[a]pyrene metabolism and DNA binding. AB - The monoclonal antibody MAb 1-68-11, prepared to constitutive cytochrome P450 IIC11 (2c/RLM5) from male Sprague-Dawley rat liver, was used to study the contribution of the class of cytochrome P450s epitopically related to P450 IIC11 to the regiospecific metabolism of benzo[a]pyrene (BP) and its binding to DNA. The effect of MAb 1-68-11 was determined on the conversion of BP to BP-9,10 dihydrodiol, BP-7,8-dihydrodiol, BP-4,5-dihydrodiol, BP phenols, and BP quinones, and on the P450-dependent DNA binding catalyzed by P450 in microsomes from uninduced male and female Wistar and Sprague-Dawley rat livers, as well as 3 methylcholanthrene- and phenobarbital (PB)-induced male Wistar rat livers. In liver microsomes from untreated male rats, MAb 1-68-11 inhibited BP-9,10 dihydrodiol formation by 80%; in liver microsomes from untreated female rats, the inhibition was 100%. BP-7,8-dihydrodiol formation was inhibited from 38 to 77% in microsomes from males and 50% in those from females. In microsomes from PB induced rats, inhibition of the 9,10-dihydrodiol and the 7,8-dihydrodiol was 90% and 73%, respectively, whereas BP-4,5-dihydrodiol formation was enhanced 80%. In microsomes from 3-methylcholanthrene-treated rats, no inhibition of MAb 1-68-11 was observed on either the metabolism of BP or its binding to DNA. In contrast, the binding of BP to DNA was completely inhibited by MAb 1-68-11 in microsomes from uninduced male Wistar rats and 70% in PB-induced microsomes. 32P postlabeling analysis showed that formation of the major stable adduct, BP diol epoxide bound at C-10 to the 2-amino of deoxyguanosine, was strongly inhibited in uninduced and PB-induced microsomes. Formation of the major labile BP-DNA adduct 7-(benzo[a]pyren-6-yl) guanine (BP-N7Gua) was inhibited about 60% in microsomes from untreated male Wistar rats. These results show that MAb 1-68-11 regiospecifically inhibits cytochrome P450 IIC11 and epitopically related P450s that metabolize BP at the 7,8 and 9,10 positions. MAb 1-68-11 also inhibits enzyme-catalyzed binding of BP to DNA in the specific formation of BP-N7Gua and adducts detected by the 32P-postlabeling technique. PMID- 1872953 TI - Long-term follow-up of children born to women immunized with tetanus toxoid during pregnancy. AB - Ten years after transplacental immunization with tetanus toxoid, the antibody responses of the immunized children to a booster immunization with 5 Lf tetanus toxoid did not differ from those of the control children. The tetanus toxoid stimulated lymphocyte proliferative responses showed that there was no tolerance to tetanus toxoid induced by transplacental immunization, and the stimulation indices suggested that there may be some long-term memory for tetanus toxoid among the T lymphocytes in children who had been transplacentally immunized by maternal immunization with a standard dose of tetanus toxoid. PMID- 1872954 TI - Role of granulated metrial gland cells in the immunology of pregnancy. PMID- 1872955 TI - Effect of sperm-antibodies on acrosome reaction of human sperm used for the hamster egg penetration assay. AB - The effect of anti-sperm antibodies (ASA) on the rate of acrosome reactions (AR) during "in vitro" capacitation of human sperm used for the hamster egg penetration assay (HEPA) was assessed. Motile sperm suspensions from donors were exposed to several sera and seminal plasma with sperm head-directed ASA, then they were washed and capacitated "in vitro." After capacitation, the proportion of acrosome-reacted viable sperm was assessed by staining with Fluoresceinated Pisum Sativum Agglutinin and supravital stain Hoechst 33258. ASA of any immunoglobulin class did not significantly affect either the AR rate, or the hamster egg penetration rate. In conclusion, interference of ASA on spontaneous AR rate during "in vitro" capacitation can not be advocated as an explanation of the impairment of the interaction of human sperm with egg or its vestments, which have been reported in several studies. PMID- 1872956 TI - Investigations concerning the relationship of ovarian eosinophilia to ovulation and luteal function in the sheep. AB - Eosinophilic leukocytes are attracted into the preovulatory follicle and regressing corpus luteum of sheep. Eosinophils produce a wide array of potent bioactive substances that could play a role in ovarian function. Circulatory eosinophils were depleted by treatment of ewes with prednisolone, thereby producing ovarian eosinopenia. Ovulation occurred in these animals. However, circulatory concentrations of progesterone during the ensuing luteal phase were less than normal. This insufficiency was attributed in part to a suppressed angiogenic response in the formative corpus luteum. Regression of the corpus luteum induced by prostaglandin F2 alpha was not affected by administration of prednisolone. Thus, an obligatory role of eosinophils in the mechanics of ovulation and luteal regression in the sheep is unlikely. PMID- 1872957 TI - Detection of sperm antibodies on unwashed spermatozoa with the immunobead test: a comparison of results with the routine method and seminal plasma TAT titers and SCMC test. AB - This study investigated whether the immunobead test (IBT) could, for the purposes of simplicity and saving time, be applied directly on an unwashed semen sample instead of washed spermatozoa. These two methods were performed simultaneously on the semen samples of 15 men with a positive MAR test and 10 men with a negative MAR test. A possible association was found between the unwashed samples, showing positive IB binding (greater than 20%) on the tail and/or head and the seminal plasma TAT titers (P less than .00001, Fisher's exact test). In all cases with IB binding of greater than or equal to 20% on unwashed spermatozoa, positive seminal plasma TAT titers (greater than or equal to 32) and SCMC tests (greater than or equal to 50%) were found. In all cases where the binding of the beads was mainly located on the tailtips of the washed or unwashed spermatozoa, negative seminal plasma TAT titers and SCMC tests were found. Coating of the head and/or upper tail regions in both methods was always associated with high TAT titers and a strong-positive SCMC test. It is concluded that the IBT for IgA, but not for IgG, can be performed directly on unwashed semen and that the position of IB binding on the spermatozoa is of prognostic importance with regard to the expected outcome of the SCMC test and seminal plasma TAT titers. PMID- 1872958 TI - [Fluorescent determination of magnolol by surfaceactive emulsifier]. AB - Fluorescent determination of magnolol has been effected employing the sensitivity and stability-enhancing action of the non-ionic surfaceactive emulsifier OP. As a result the accuracy of determination is raised by 2 orders of magnitude as compared to that of ultraviolet spectrophotometry. PMID- 1872959 TI - [Quantitative analysis of bergenin in herba Ardisia japonica Bl by TLC densitometric method]. AB - A method for the determination of bergenin content in Herba Ardisia japonica was established by the use of TLC-densitometry. The method is sensitive, simple and convenient, with a recovery of 101.2%. PMID- 1872960 TI - [Pharmacological action of cultured calculus bovis]. AB - By means of comparative pharmacological study, the main pharmacodynamics and toxicity of cultured calculus bovis and natural calculus bovis were compared under the same conditions. The results show that both drugs possess sedative, antispasmodic, antipyretic, antiinflammatory, cardiotonic and hypotensive effects, the strength of effect and toxicity being similar. PMID- 1872961 TI - [Anti-cholinesterase activity of fordine]. AB - The inhibitory effect of fordine on human true cholinesterase (ChE) was found to be 55386 times larger than on pseudo ChE in vitro. There was a marked difference in the inhibition of fordine on pseudo ChE of different species. The order of the decrease of potency of fordine on true ChE of different species was man, dog, rabbit, cat, rat and mouse. The order of the decrease of potency on pseudo ChE was rabbit, rat, dog, cat, mouse and man. In vivo, it was shown that ChE in blood and brain was strongly inhibited by fordine, and the duration of the inhibitory action was comparatively long. The ChE activity inhibited by fordine may recover spontaneously. PMID- 1872963 TI - [Advances in the pharmacological researches on the commonly-used prescriptions in Chinese traditional medicine during past 5 years]. PMID- 1872962 TI - [Review of experimental researches on the compatibility of drugs in a prescription]. PMID- 1872964 TI - [Some herbal textual comments on tianmingjing (Carpesium abrotanoides L.)]. AB - This paper deals with the Bencaological records of the traditional Chinese drug Tianmingjing and the reason for its different names in use today. The traditional Chinese drug Heshi should be the fruit of Artemisia cina, rather than that of Carpesium abrotanoides. The present application of Tianmingjing in China is also discussed. PMID- 1872965 TI - [Identification of Schisardra by TLC-densitometry]. AB - This paper deals with the determination of the lignins in 10 species of Schisandra crude drugs by TLC-densitometry. The result shows that all the 10 species are unidentical in the lignin constituents; the same species vary in the contents with habitats; and the TLC chromatograms of the 10 species differ distinctly from each other. PMID- 1872966 TI - [Pharmacognostical study on the Chinese drug nanshashen]. AB - The Chinese drug nanshashen is taken from a variety of plants. In this paper, 11 kinds of nanshashen derived from 11 plants of Adenophora have been studied in their pharmacognostical characters and microproperties. A key has been compiled based on the experimental results. PMID- 1872967 TI - [The preservation capacity of water and fertility of soilless cultivation substrate for Panax quinquefolium L.)]. AB - The preservation capacity of water and fertility of several soilless cultivation substrates for Panax quinquefolium was compared in a large area. The data indicate that vermiculite mixed with sand (volume 1:1) is the most suitable soilless substrate for P. quinquefolium, for it is loose and features good preservation of fertility, water retaining, drainage, and air permeability. Timely analysis of nutrient contents in the substrates during cultivating period may serve as a guideline for correct application of fertilizer. PMID- 1872968 TI - [Analytical studies on amino acids and trace elements in donkey-hide gelatin]. AB - This paper reports the contents of amino acids in donkey-hide gelatin made in different pharmaceutical factories before and after processing. An analytical comparison of trace elements in the gelatin is also presented. PMID- 1872969 TI - [Trace elements in the aqueous extract of twenty Chinese drugs before and after charring]. AB - Our study on the variation of trace element contents in the aqueous extract of 20 Chinese drugs before and after charring has shown that after charring Ca ions increase noticeably in the extract of 6 drugs, increase slightly in another 6 and decrease in varying degrees in the remaining 8. In all the charred drugs no rise has been observed in the contents of trace elements, but instead, in most of them the contents tend to drop. PMID- 1872970 TI - [Content of astraglin A in zhongfeng naomai tong oral liquid]. AB - Using HPTLC-scanning method, the contents of astraglin A in four kinds of zhongfeng naomai tong oral liquid have been determined to be 0.0018-0.0022%. Simple and easy to use the method is recommended for the quality control of compound preparations containing huangqi. PMID- 1872971 TI - [Experimental study on usage and dosage of gypsum]. AB - The content of calcium ion Ca2+ in gypsum decoction has been determined with coordination titration. Observation and comparison have been conducted of the relationship between the dosage, comminution degree, decocting time and decocted contents. The results show that the dosage of gypsum should be 10-20 grams, preferably ground to at least 60 mesh powder, the fine powder over 60 mesh is not to be pre-decocted, but the coarse powder of 40 mesh needs pre-decocting. PMID- 1872972 TI - [Chemical constituents of the pericarp of Trichosanthes rosthornii Harms]. AB - Nine compounds were isolated from the pericarp of T. rosthornii and identified on the basis of spectral data to be palmitic acid, lignoceric acid, cerotic acid, montanic acid, melissic acid, L-(-)-alpha-monopalmitin, delta 7-stigmastenol, delta 7-stigmastenone-3 and delta 7-stigmatenol-3-beta-D-glucopyranoside. All but the last one are obtained from this species for the first time. PMID- 1872973 TI - [Chemical constituents of Osbeckia chinensis L]. AB - Five constituents, 2-furoic acid, succinic acid, ursolic acid, quercetin and daucosterol were isolated and identified from Osbeckia chinensis. All of them are reported to have been found from this plant for the first time. PMID- 1872974 TI - The efficacy of six heel pressure reducing devices. AB - Twenty to 90 percent of pressure ulcers are located on the heel. The purpose of this study was to evaluate the pressure exerted on the heel when the foot in both the supine and the 30 degree elevated position was placed in various heel pressure reducing devices. Interface pressures of six heel devices were measured to determine their performance. Other factors, such as body weight, height shoe size, shoe width, as well as whether the device provided leg support were examined. PMID- 1872975 TI - Incidence and prediction of pressure ulcers in five patient care settings. AB - Pressure ulcers (PU), one example of an alteration in skin integrity, remain a prominent healthcare concern in all patient care settings. Incidence refers to the number of "new cases occurring over a given time period" (NPUAP, 1989, p. 26). Adult patients (n = 190) in five patient care settings who were assessed to be free of PUs on admission were followed over a specified period of time to assess the incidence of pressure ulcer development for each setting. Subjects each had a skin assessment, along with a risk assessment utilizing the Braden Scale. A demographic data form was also completed on each subject. Pressure ulcers developed post-admission in 18 (9%) patients, 11 of whom were acute care patients and eight of whom were patients in skilled care. No patients developed pressure ulcers in the rehabilitation, home care, or hospice settings. Incidence for acute care was 15% and 28% in skilled care. Braden predictor scores were also recommended for each setting and factors associated with pressure ulcer development were discussed. PMID- 1872976 TI - Healthcare reform. PMID- 1872977 TI - Evaluation of an alginate dressing for pressure ulcers. AB - Pressure ulcers that secrete moderate to large amounts of fluid often cause leakage from under dressings, odor, staining of clothing, denuding of the skin, and pain. Two highly absorbent dressings derived from seaweed have been introduced into the U.S. market for use in the management of exuding wounds. Severely debilitated patients with full-thickness pressure ulcers were treated for one week to three months with one of these alginate dressings (Kaltostat). The handling and performance characteristics of the dressing are discussed. PMID- 1872978 TI - Anemia is a factor of great significance in determining whether or not cellular hypoxia and necrosis. PMID- 1872979 TI - ['An enormous award'--Muntendam Prize for nurse Els Koldewijn. Interview by Toine de Graaf]. PMID- 1872980 TI - [The law on disposal of the dead and the nurse]. PMID- 1872981 TI - [Hospital Rijnstate Arnhem. Creatively made-to-measure]. PMID- 1872982 TI - [Mentally handicapped, sexuality and relations (2). Viewpoint and policy in residential facilities]. PMID- 1872983 TI - [Environment--from the district nursing practice]. PMID- 1872984 TI - [Does home care require differentiation and specialization in district nursing?]. PMID- 1872985 TI - Morphine increases intake of beer among rats. AB - Rats were maintained on a daily regimen of 22 h of water deprivation followed by a 2-h opportunity to take water and sweetened alcoholic beverage containing 12% ethanol. After 30 days, the alcoholic beverage was changed to beer containing either 3% or 6% ethanol. After 20 daily sessions with beer, they received, before the next session, an injection of saline. On the next day, they received a 1.0 mg/kg injection of morphine before the session. Morphine reliably increased rats' mean intake of both kinds of beer. Subsequently, the concentration of ethanol in each groups' beer was changed. The 3% group's beer was switched to 6%, and the 6% group's to 3%. Both groups altered their mean intake of beer in an apparent attempt to maintain intakes of nearly the same amount of ethanol, but presentation of 6% beer resulted in greater intakes of ethanol. PMID- 1872986 TI - Effects of prenatal ethanol exposure on postnatal renal function and structure in the rat. AB - Effects of prenatal ethanol exposure on postnatal renal function and structure in the rat. Renal function and morphology were studied in 90-day-old offspring of ethanol-fed (E) rats and were compared to pair-fed control (C) animals. Compared to C rats, E rats were smaller at birth, had higher fractional sodium excretion (p less than 0.01) and lower fractional potassium excretion (p less than 0.01). In E rats, sodium (Na) restriction resulted in a significant increase in urine flow and Na wastage, whereas C rats remained in Na balance. E rats developed hyperkalemia, when potassium (K) intake was increased from 2.8 to 14 mEq/day. Baseline creatinine clearance, urine and blood osmolalities and pH, plasma electrolytes and aldosterone concentrations were similar in both groups. There was no significant difference in wet or dry kidney weight, renal water content, or renal tissue concentrations of Na or K between the two groups. No difference was found in gross morphology or light microscopic appearances of the kidneys between E and C rats. Thus rats exposed to ethanol during fetal life have a defect in urine concentration and Na conservation when fed a low Na diet and a defect in K excretion when given a K load without evidence of any gross or light microscopic renal structural abnormalities at 90 days of age. PMID- 1872987 TI - The effects of chronic alcohol consumption or thiamin deficiency on radial-arm maze performance in the rat. AB - Experiment 1 tested the hypothesis that chronic consumption of ethanol, in the presence of good nutrition, is associated with impairments in memory. Rats were fed a vitamin-fortified ethanol-Sustagen diet with 35% ethanol-derived calories for 150 days. Two control groups were used. The first was pair fed a Sustagen mix in which sucrose had been substituted for ethanol. The second control group received ad lib access to standard laboratory chow and water. All animals were then placed on the chow and water diet for six weeks prior to testing in an eight arm radial maze. There was a significant, but modest, difference between groups in the number of trials to reach a criterion level of seven correct from the first eight choices and all eight correct in ten choices. However, there were no differences between the groups when delays (0, 5, 20, 60, 120 and 240 minutes) were imposed between the 4th and 5th choices. In Experiment 2, a thiamin deficient group was compared with pair-fed and ad lib control groups on the same task. The thiamin-deficient group took more trials to reach criterion but the groups did not differ in the delay testing phase. The results are discussed in the context of reference/working memory distinctions, and the literature on remediation of cognitive deficits associated with alcoholism. PMID- 1872988 TI - Vitamin E reduction of lipid peroxidation products in rats fed cod liver oil and ethanol. AB - The purpose of this study was to investigate the effects of vitamin E supplementation on ethanol- and cod liver oil-induced lipid peroxidation. Adult male rats received diets containing ethanol, cod liver oil and supplemented with vitamin E for 28 days. Following treatment, hepatic conjugated dienes, lipid fluorescence, and exhalation of ethane were measured as indices of lipid peroxidation. Ethane expiration over a 3-hour period was reduced by 96% in rats fed ethanol supplemented with vitamin E. Exhalation of ethane was increased by CLO feeding but was reduced 89% in the CLO-fed rats supplemented with vitamin E. In addition, ethane production was elevated in rats fed ethanol plus CLO compared to rats fed diets containing CLO supplemented with vitamin E. Supplementation of the CLO diet with vitamin E also significantly decreased hepatic conjugated fatty acid dienes levels. Levels of hepatic conjugated fatty acid dienes from rats fed ethanol plus vitamin E were reduced 91% compared to rats fed ethanol diets. Additionally, hepatic lipid fluorescence expressed as per mg of hepatic phospholipid basis was also significantly increased in rat groups fed vitamin E, ethanol, and cod liver oil diets. Where vitamin E was added to these same diets a significant decrease of hepatic lipid peroxidation products occurred. The observed reduction in lipid peroxidation by vitamin E may be useful to retard lipid peroxides derived materials involved in the development of alcoholic liver diseases. PMID- 1872989 TI - Effect of 3-amino-1,2,4-triazole on the hypothermic effect of ethanol and on ethanol tolerance development. AB - The effect of aminotriazole (AT), inhibitor of catalase activity, on hypothermia and narcosis induced by ethanol and on the acquisition of tolerance to the ethanol hypothermic and narcotic effect was studied. Rats were pretreated with AT (1 g/kg IP) 1 hour before the test dose of ethanol (2.76 g/kg IP) and narcosis time, hypothermia and ethanol blood levels evaluated (first test). For studies on tolerance to ethanol, rats of the first test received daily (for 7 days) a dose of AT (1 g/kg IP) 1 hour before ethanol (2.76 g/kg) given by gavage, and the same parameters evaluated (8th day test). Results were compared to similar groups of rats without AT pretreatment (controls, 1st and 8th day test). Rats pretreated with AT exhibited a shorter narcosis time induced by ethanol but this treatment did not alter the hypothermic effect of ethanol nor ethanol disposal rate. Chronic ethanol treatment induced tolerance to the narcotic and hypothermic effect of ethanol as well as a metabolic tolerance. AT administered daily before the dose of ethanol produced a partial blockade of the development of tolerance to the narcotic effect of ethanol, but did not alter the development of hypothermic or metabolic tolerance. The brain catalase system seems to play a role in narcosis and on the development of tolerance to this effect of ethanol, but not in the hypothermic effect or in the development of tolerance to this ethanol effect. Since the inhibition of liver catalase activity by AT treatment was not correlated with changes in ethanol disposal rate, the liver catalase system appears not to play a role in the metabolic tolerance. PMID- 1872990 TI - Putative type II alcoholism characteristics in female third DUI offenders in Massachusetts: a pilot study. AB - Women who come to the attention of the courts may exhibit heritable Type II alcoholism. Accumulating evidence indicates that more women report having alcoholic parents, that onset of women's alcohol problems before age 25 predicts greater severity of alcohol problems, that women most frequently acknowledge driving while intoxicated (DUI) as an alcohol-related problem, and that the percent of female arrests for DUI has increased. Alcoholic men have been classified as Type I (onset after age 25 and environmentally influenced) or Type II (onset before age 25 with impulsivity and criminal activity) alcoholics. Alcoholism in daughters of Type I fathers is said to occur after age 25 and to be shaped by environmental conditions, but it has been argued that daughters of Type II alcoholic fathers express their family histories in somatization. We report results from a pilot study that found putative Type II alcoholism characteristics, including early age of onset and inability to curtail drinking, in a sample of 12 incarcerated female third DUI offenders. PMID- 1872991 TI - Role of the sympathetic nervous system in ethanol-induced hypertension in rats. AB - The present study investigated the role of the sympathetic nervous system in the development of ethanol-induced hypertension (EIH) in the rat. Sympathetic nerve activity (SNA) as an index of central sympathetic tone was measured directly from the preganglionic fibers of the greater splanchnic nerve. Four weeks after starting ethanol feeding, and prior to the development of hypertension, SNA of the ethanol-fed rats was significantly greater than that of controls. The increase in SNA was also evident at the early stages of EIH, at 8 weeks, and in fully developed EIH, after 12 weeks of ethanol consumption. Baroreceptor reflex control of heart rate (HR) but not SNA was impaired prior to the development of EIH at 4 weeks. However, at 8 and 12 weeks, baroreflex control of HR and SNA was normal or slightly greater than that of control rats. Because arterial pressure of ethanol-fed rats was significantly higher than that of controls at 8 and 12 weeks, the data suggest that ethanol feeding caused baroreceptor resetting. Pressor responsiveness to phenylephrine was depressed before the development of EIH but was similar to that of control rats following the development of EIH. The data also shows that blood and plasma volumes of ethanol-fed rats at the times that coincided with the pre- and posthypertensive states were similar to those of control rats which suggests that the development of EIH does not involve an increase in plasma volume. It is concluded that an increase in SNA contributes to the development of EIH and that baroreceptor resetting evoked by ethanol feeding plays a permissive role in maintaining an elevated blood pressure in ethanol-fed rats. PMID- 1872992 TI - Fat-preferring rats consume more alcohol than carbohydrate-preferring rats. AB - Rats with a genetic preference for alcohol (ETOH) have been found to consume more dietary fat then ETOH nonpreferring rats. We therefore hypothesized that rats selected on the basis of fat and carbohydrate (CHO) preferences would differ in ETOH intake. Patterns of macronutrient self-selection were determined by allowing rats to select diets from separate sources of CHO, fat and protein. Subsequently, CHO- and fat-preferring groups were formed. All rats were then returned to a lab chow diet and trained to drink ETOH (4-12%) during one hour of access per day. Food restriction was used only in the first three weeks of the procedure. On the final drinking sessions, water and ETOH were alternated on a daily basis. Fat preferring rats consumed significantly more ETOH than water; CHO-preferring rats consumed approximately equal amounts of ETOH and water. Furthermore, fat preferring rats consumed more ETOH than CHO-preferring rats. This study suggests that there may be a common mechanism underlying diet preference and oral intake of ETOH. PMID- 1872993 TI - Tetrahydropapaveroline and the blood-brain barrier in rats. AB - The blood-brain barrier penetration of tetrahydropapaveroline (THP) was studied in male rats of the Sprague-Dawley strain. THP was not found in brains of untreated animals. However, THP was observed in the brains of animals that received THP.HBr by intraperitoneal (IP) injection 30 minutes before decapitation. Animals that received IP injections of 0.10, 1.0, 5.0, or 10 mg THP.HBr/kg exhibited brain levels of 3.1, 25, 95 or 126 pmoles THP per gram brain, respectively. Another group of rats received THP.HBr (5.0 mg/kg) IP 30 minutes before decapitation. The brain of each animal was dissected into nine regions and each region assayed for THP. All brain regions assayed had measurable levels of THP. The highest concentration of THP (132 pmoles/g) was observed in the olfactory lobes-frontal cortex while the lowest concentration of THP (27.3 pmol/g) was in the striatum. These results demonstrate that THP penetrates the blood-brain barrier in rats. They also suggest that if THP is formed in the periphery, it may penetrate the blood-brain barrier, and be localized in discrete brain regions. PMID- 1872994 TI - Event-related potentials in alcoholic fathers and their sons. AB - ERPs were recorded during a simple color discrimination and a more difficult visual continuous performance task (CPT) from three father-son (n = 15) pair groups: recovering alcoholics with a family history of alcoholism and their sons (A+), nonalcoholics with a family history of alcoholism and their sons (NA+), and nonalcoholics with no family history of alcoholism and their sons (NA-). The sons, aged 8 to 12, had not begun drinking or using other drugs. Groups were matched on age, education and socioeconomic status. There were two principal findings. Compared to nonalcoholic groups, both A+ sons and fathers exhibited increased latency and decreased amplitude of P3 for the difficult task, but not for the easy task. This result helps to explain previous inconsistencies in the literature, and strengthens the suggestion that one indication of a vulnerability to develop alcoholism is an abnormal P3, when elicited by an appropriate task. Additionally, A+ fathers had more negative amplitudes for a late slow wave in both tasks, suggesting electrophysiological consequences of long-term alcohol abuse. PMID- 1872995 TI - Synthesis and properties of (R)-2-hydroxyglutaryl-1-CoA. (R)-2-hydroxyglutaryl-5 CoA, an erroneous product of glutaconate CoA-transferase. AB - 1) (R)-2-Hydroxyglutaryl-1-CoA was synthesised starting from (R)-5 oxotetrahydrofuran-2-carboxylic acid (gamma-lactone of (R)-2-hydroxyglutarate) which was converted to the acylchloride and condensed with N-capryloylcysteamine. The lactone ring of the resulting thiolester was opened by acid hydrolysis and the CoA derivative was obtained by transesterification. 2) Pure glutaconate CoA transferase from Acidaminococcus fermentans catalysed the formation of the 1- and the 5-isomer of (R)-2-hydroxyglutaryl-CoA from acetyl-CoA and (R)-2 hydroxyglutarate. The isomers were separated by HPLC and characterised by their reaction with acetate under the catalysis of the CoA-transferase. V/Km for the 1 isomer was 80 times higher than that for the 5-isomer. 3) Studies with cell-free extracts from A. fermentans showed that only (R)-2-hydroxyglutaryl-1-CoA but not its 5-isomer was dehydrated to glutaconyl-1-CoA. The data indicate that (R)-2 hydroxyglutaryl-5-CoA is an erroneous product of glutaconate CoA-transferase which only occurs in vitro. PMID- 1872996 TI - Novel metabolite structures from biotransformation of a sesquiterpenoid ketone by selected fungal strains. AB - The sesquiterpenoid ketone, 1,4,4-trimethyltricyclo[5.4.0.0(3.5)]undec-7-en-9-one (1), was subjected to microbial transformation by six fungal strains: Aspergillus niger ATCC 9142, Aspergillus ochraceus DSM 824, Beauveria bassiana ATCC 7159, Cunninghamella echinulata ATCC 9244, Rhizopus arrhizus ATCC 11.145, and Absidia blakesleeana ATCC 10.148. Four main metabolites were formed from 1: 10(R)- and 10(S)-hydroxy-1,4,4-trimethyltricyclo-[5.4.0.0(3.5)]undec-7- en- 9-one (2 and 3, respectively), besides 4(R)- and 4(S)-(hydroxymethyl)-1,4 dimethyltricyclo[5.4.0.0(3.5)]undec -7-en-9-one (4 and 5, respectively). Compounds 2-5 were isolated with varying percentages from the respective transformations, and their structures established unequivocally by a combination of spectroscopic methods. Metabolites 2 and 3 are products of hydroxylation at C 10, in either R- or S-position; in 4 and 5, one geminal CH3 group each on the cyclopropane ring has been transformed into a CH2OH function. PMID- 1872997 TI - Effect of vanadate on the metabolism of bile acids in diabetic rats. AB - The effect of treatment with vanadate on the metabolism of bile acids was studied in normal and diabetic rats. In the normal rats, the composition of biliary bile acids was not changed by drinking an aqueous solution of 0.2 g/l NaVO3-5 g/l NaCl ad libitum for two weeks. By contrast, the increased proportion of cholic acid, accounting for 88% of the total biliary bile acids, in the diabetic rats decreased to 46% by the treatment with vanadate without any elevation of serum insulin level. These results indicate that vanadate with an insulin-like effect on glucose metabolism in diabetic rats has such an effect also on bile acid metabolism in an insulin-deficient state. PMID- 1872998 TI - Microsequencing of proteins and peptides in the Knauer sequencer with and without covalent attachment to polyvinylidene difluoride membranes by the wet-phase degradation technique. AB - Proteins and large peptides were degraded with phenylisothiocyanate (PITC) in the horizontal flow-through-reactor of the Modular Knauer Sequencer (Fischer, S., Reimann, F. & Wittmann-Liebold, B. (1989) in Methods in Protein Sequence Analysis (Wittmann-Liebold, B., ed.) Springer-Verlag, Berlin, pp. 98-107) by the wet-phase filter technique (Wittmann-Liebold, B. (1988) J. Prot. Chem. 7, 224-225) employing polyvinylidene difluoride (PVDF) membranes without polybrene. In order to prevent losses of small peptides during solvent washes at the degradation, 1.4 phenylene diisothiocyanate (DITC) derivatized PVDF support (MilliGen, Burlington, MA) was used to covalently attach the peptide via its lysine groups in situ within the cross-flow reaction chamber onto this membrane (Herfurth, E., Pilling, U. & Wittmann-Liebold, B. (1990) J. Prot. Chem. 9, 267). We found these membranes very suitable for peptide degradations in the Knauer sequencer. In almost all cases we were able to identify the amino-acid residues of the peptide up to its last covalent fixation point to the membrane. PMID- 1872999 TI - Structure and function of L-lactate dehydrogenases from thermophilic and mesophilic bacteria, XI. Engineering thermostability and activity of lactate dehydrogenases from bacilli. AB - An extensive comparative structural analysis of lactate dehydrogenase (LDH) sequences from thermophilic, mesophilic and psychrophilic bacilli revealed characteristic primary structural differences. These specific amino-acid substitutions were found in the entire LDH molecule. However, in certain regions of the LDH an accumulation of these exchanges could be detected. These regions seem to be particularly important for the temperature adaptation of the enzyme. The influence of one of such regions at the N-terminus on stability and activity of LDHs was analysed by the construction of hybrid mutants between LDH sequences from thermophilic, mesophilic and psychrophilic bacilli and also by site-directed mutagenesis experiments at five different positions. The substitutions of Thr-29 or Ser-39 to Ala residues in the LDH from the mesophilic B. megaterium increased the thermostability of the enzyme drastically (15 degrees C). An increase of 20 degrees C could be observed when both amino-acid substitutions were introduced. These amino-acid substitutions resulted in an increase of Km for pyruvate and led to a three-fold reduction of the activity (kcat/Km) at 40 degrees C compared with the wild type enzyme. The influence of these amino-acid substitutions was also investigated in the LDHs from thermophilic and psychrophilic bacilli. The high heat resistance of the LDH from the thermophilic B. stearothermophilus was not altered by the Ala to Thr and Ser substitutions at positions 29 and 39, respectively. This indicates a cooperatively stabilized conformation of this LDH. However, in this mutant of the B. stearothermophilus LDH the activity (kcat/Km) was increased two-fold. PMID- 1873000 TI - Immunohistochemical analysis of the ontogeny of calcitonin gene-related peptide like immunoreactivity in the rat central nervous system. AB - The ontogeny of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) in the rat central nervous system was examined using the indirect immunofluorescence technique. Caudally located neurons displayed CGRP-LI relatively early in development. For instance, CGRP-immunoreactive (CGRP-IR) cells were first visualized in the hypoglossal nucleus and dorsal nucleus of the lateral lemniscus at day 19 of gestation, while by day 1 postnatal the facial and ambiguus nuclei possessed their full complement of immunoreactive neurons relative to that observed in the adult. By contrast, CGRP-IR somata in more rostral regions such as the lateral septal nucleus were not visualized until much later in development, i.e. day 12 postnatal. By day 15 postnatal, however, CGRP LI was at a maximum in almost all areas scrutinized. This pattern of immunostaining persisted up to the oldest age studied (day 28 postnatal), except in the lateral septal and parabrachial nuclei, along the dorsal border of the medial lemniscus, and in the inferior olive, where many of the previously immunopositive cells could no longer be detected. In summary, CGRP-IR somata in the rat central nervous system appear in a principally caudal to rostal direction, beginning in late gestation. In some regions, CGRP is present only ephemerally. The ontogeny of CGRP during maturation of the rat brain is consistent with its suggested neurotrophic and neurotransmitter roles. PMID- 1873001 TI - Dopamine-beta-hydroxylase-positive nerves in normal and transplanted pancreatic tissue in the anterior eye-chamber of rats. AB - Dopamine-beta-hydroxylase(DBH)-positive nerves were demonstrated in normal and in pancreatic tissue fragments transplanted for 22 and 32 days into the anterior eye chamber of rats using immunohistochemical techniques. Dopamine-beta-hydroxylase immunopositive neurons of different shapes could be observed in normal pancreas. The neurons had either spindle or oval shapes. In the transplanted tissue, DBH positive neuronal profiles were found in the stroma. In some cases DBH immunopositive cells appeared as a cluster of cells around pancreatic ducts and blood vessels or as solitary cells. The wall of pancreatic ducts in the transplants also contained DBH-immunopositive nerve profiles. PMID- 1873002 TI - Effects of a sodium-potassium ion-exchanging seaweed preparation in mild hypertension. AB - A nonpharmacological approach in the treatment of mild hypertension is often advocated. In an attempt to decrease sodium and increase potassium intake, sixty two middle-aged patients with mild hypertension were given a potassium loaded ion exchanging sodium-adsorbing potassium-releasing seaweed preparation (seaweed fiber, SF). The mean blood pressure (MBP), evaluated in a double-blind crossover manner with four weeks familiarization and wash-out periods, showed a significant decrease after four weeks on 12 and 24 g/day SF but not on 6 g/day or placebo treatment. Systolic blood pressure during submaximal exercise decreased on all three SF doses. The decrease in MBP appeared to be significantly higher in sodium sensitive (11.2 mm Hg, P less than .001) than in sodium-insensitive (5.7 mm Hg, P less than .05) patients and was in salt-sensitive patients significantly correlated to the increase in plasma renin activity (PRA). The urinary sodium excretion decreased, the urinary potassium increased and the sodium/potassium urinary excretion ratio decreased, indicating that the decrease of MBP was dependent on the decreased intestinal absorption of sodium and increased absorption of potassium released from the seaweed preparation. A sodium-potassium ion-exchanging seaweed preparation is an effective means of decreasing sodium and increasing potassium intake, and may be used for antihypertensive treatment in mild hypertension. PMID- 1873003 TI - Double-blind comparison of perindopril and captopril in hypertension. Effects on left ventricular morphology and function. AB - Using digitized M-mode echocardiograms, we compared, in a double-blind study, the effects of 4 to 8 mg perindopril given once daily and 25 to 50 mg captopril given twice daily on the left ventricle (LV) in 20 hypertensive patients. Both treatments significantly (P less than .001) lowered blood pressure, reducing systemic vascular resistances. After 3 months both drugs induced a comparable percentage of reduction in LV mass, with an increase in the peak rate of LV relaxation and no changes in the peak rate of LV contraction. Our results demonstrate that perindopril once daily is an effective antihypertensive agent; it is also able, like captopril, to induce regression of LV hypertrophy, with improvement in diastolic performance and no deterioration in ventricular systolic function. PMID- 1873004 TI - Ambulatory blood pressure variation is related to plasma renin activity in borderline hypertensive men. AB - The purpose of this study was to examine the relationship between the variability of awake ambulatory blood pressure and the level of plasma renin activity (PRA) in age-matched samples of untreated hypertensive white men. The ambulatory pressures of 376 men (145 under 45 years of age, 231 over 45) were compared across three levels of PRA: less than 1.0 ng/mL/h, 1.0 to 4.0 ng/mL/h and 4.0 ng/mL/h or greater. The results showed that the average diastolic pressure declined with PRA, particularly in men under 45 (95 to 89; P less than .05), but that among the men 45 and older there was a strong, positive relationship between awake diastolic pressure variability and the level of PRA (p less than .001). These results may have important clinical implications since both higher PRA and greater blood pressure variability have been associated with a greater cardiovascular disease risk. PMID- 1873005 TI - Association between plasma viscosity and blood pressure. Results from the MONICA project Augsburg. AB - The relationship between determinants of blood viscosity and blood pressure (BP) variables was studied in a large sample of a population aged 25 to 64 years. Plasma viscosity, hemoglobin, and total serum protein were examined. Systolic and diastolic BP and the prevalence of hypertension showed a crude positive association with plasma viscosity levels in both sexes. Age, body mass index, and total serum protein appeared to have a confounding effect on this relationship, whereas hemoglobin, smoking behavior, and alcohol consumption did not. A crude positive association was also found between total serum protein levels and the prevalence of hypertension in men and women; however, since total serum protein was treated as a covariable, no further analyses were carried out. In contrast to findings reported in the literature, hemoglobin levels were not correlated with BP variables in either sex. After adjusting for all confounders, a significant main effect of plasma viscosity still was found. However, the magnitude of the effect was not as large as for body mass index, a well-established risk variable for hypertension. These results indicate that BP is positively associated with plasma viscosity. Whether increased plasma viscosity in hypertension constitutes a primary or a secondary phenomenon remains to be answered. Since plasma viscosity is significantly associated with hypertension but any BP variable, increased levels of plasma proteins (particularly fibrinogen as the main determinant of plasma viscosity) may represent the cause for elevated plasma viscosity. This might contribute to persistently increased resistance to blood flow on the microcirculatory level in arterial hypertension. PMID- 1873006 TI - Insulin attenuation of vasoconstrictor responses to phenylephrine in Zucker lean and obese rats. AB - Recent data from this laboratory indicate that insulin resistant obese Zucker rats exhibit hypertension associated with exaggerated in vitro vascular reactivity to phenylephrine, serotonin, and KCl, and we have found insulin to attenuate vascular reactivity responses to these agonists. Accordingly, in the present study we evaluated the possibility that exaggerated vascular reactivity responses in obese Zucker rats may result from insulin resistance and a consequent failure of insulin to attenuate vasoactive responses. Thoracic aortae were isolated from male 16 week old lean and obese Zucker rats, and replicate helical strips from each animal were suspended in a muscle bath under a resting tension of 1.4 g in the presence or absence of insulin (0.1 mU/mL) for 1 h. The insulin was then washed out, and vascular reactivity responses to phenylephrine were determined. The obese rats exhibited greater reactivity to phenylephrine (ED50:1.10 +/- 90 X 10(-8) v 7.57 +/- 0.88 X 10(-10) mol/L in lean and obese rats, respectively, P less than .025). Insulin caused a significant attenuation of the contractile response in both the lean and obese aortae. However, lean rats exhibited a markedly greater attenuation than the obese rats (46.0 +/- 17.0 v 17.8 +/- 7.5% attenuation in the lean and obese rats, respectively, P less than .01). These data suggest that increased vascular reactivity responses in obese Zucker rats may result from their insulin resistant state and, consequently, a diminished ability of insulin to attenuate vasoconstrictor responses. PMID- 1873007 TI - Human platelet calcium measurements. Methodological considerations and comparisons with calcium mobilization in vascular smooth muscle cells. AB - Platelets are used as models for vascular smooth muscle cells (VSMC) in evaluating intracellular calcium ([Ca2+]i) metabolism in humans. This study was designed to determine if agonist-induced increases in [Ca2+]i in platelets occur via release from intracellular stores as previously demonstrated for VSMC. Incubation of purified platelets loaded with fura-2-AM in media containing 1.5 mmol/L Ca2+ resulted in higher basal [Ca2+]i than platelets incubated in Ca(2+) free media. In addition, vasopressin-induced platelet [Ca2+]i transients were almost completely blocked by Ca2+ channel blockers. Thus, in contrast to VSMC, the transmembranous flux of extracellular Ca2+ is the major mechanism in vasopressin-induced increases in platelet [Ca2+]i, while mobilization of intracellular Ca2+ stores is only minimally involved. PMID- 1873008 TI - Duplex ultrasound in the assessment of vascular disease in clinical hypertension. AB - Duplex ultrasound combines B-mode imaging and pulsed Doppler flow analysis and is rapidly becoming the most useful and widely applied method for the evaluation of atherosclerotic arterial disease. Recent technical improvements including color flow Doppler allow its application to practically all vascular beds in the body. Duplex is noninvasive and in many areas its accuracy in the detection of arterial stenosis and occlusion rivals angiography. Duplex ultrasound has become the preferred method of evaluation of patients with cerebrovascular disease. It provides information about the degree of stenosis, location of disease, and plaque characterization, and in many cases replaces standard cerebral arteriography. Duplex ultrasound has been used to detect renal artery stenosis in patients suspected of having renovascular hypertension with an accuracy of 93% in the diagnosis of hemodynamically significant stenosis. It also has important applications in the assessment of mesenteric artery stenosis, peripheral vascular disease, and venous disease. Because it is accurate, reasonably inexpensive, and noninvasive, duplex ultrasound can be used to follow the progression of untreated atherosclerotic lesions throughout the body. Used in this fashion, it provides important information about the natural history of atherosclerotic lesions, their clinical prognosis, and the effect of interventions, either medical or surgical, on lesions. PMID- 1873009 TI - Calcium metabolism and dietary calcium in salt sensitive hypertension. AB - Evidence has accumulated over the past decade that suggests a relationship between low calcium intake, abnormalities in cation metabolism and hypertension in certain segments of the essential hypertension population. This evidence has been developed from epidemiological data, calcium intervention trials and observations related to biochemical alterations suggestive of a calcium deficiency in certain patients with hypertension and in animal models of essential hypertension. It is becoming increasingly evident that salt sensitive individuals are especially likely to be characterized by abnormalities of calcium metabolism and blood pressure responses to dietary calcium. In this review the role of calcium in the regulation of blood pressure is examined with an emphasis on epidemiological, biochemical, hemodynamic and dietary intervention data in the salt sensitive hypertensive patient. PMID- 1873010 TI - Normal serum levels of calcitonin gene-related peptide (CGRP) in mild to moderate essential hypertension. AB - Calcitonin gene-related peptide (CGRP), a highly potent vasodilator, is expressed from the calcitonin-gene and has been localized to nerve fibers of the cardiovascular system, suggesting involvement in the physiologic regulation of vascular tone. In this investigation serum concentrations of CGRP were measured in patients with untreated mild to moderate essential hypertension (WHO I-II) and compared with concentrations in sex- and age-matched normal controls to assess a possible relationship between changes in concentrations of CGRP and this condition. The study showed no significant difference in concentrations of CGRP between patients and the normotensive controls. However, a weak but significant positive correlation was found between systolic (SBP), diastolic (DBP), mean blood pressures (MBP), and circulating concentrations of CGRP when calculated for all individuals included in the study. No correlation was found between heart rates (HR) and concentrations of CGRP. In the normotensive control group, but not in patients with hypertension, a significant positive correlation was present between body weights and concentrations of CGRP. These findings do not support the hypothesis that low expression of CGRP plays a causal role in essential hypertension, but the results do not exclude a potential receptor defect for CGRP to be involved in the disease. PMID- 1873011 TI - Blunted renal sodium excretion during acute saline loading in normotensive men with positive family histories of hypertension. AB - The natriuretic and intra-arterial blood pressure response to an acute saline load (1000 mL 0.9% NaCl), was studied in normotensive young men with positive (n = 11) and negative (n = 21) family histories of hypertension. The age-matched (36 +/- 5 years) control group with negative family histories of hypertension was subdivided into two groups, one matched for body mass index (BMI) to the subjects with positive family histories of hypertension (n = 10), and another lean control group (n = 11). Baseline blood pressure was significantly higher in subjects with positive family histories of hypertension and in controls matched for BMI as compared with lean controls. Sodium excretion increased in all three groups during the saline infusion, while subjects with positive family histories of hypertension disclosed a diminished natriuretic response as compared with the two control groups. Systolic blood pressure increased significantly during the saline load in subjects with positive family histories of hypertension, while in subjects with negative family histories of hypertension, no significant change in blood pressure was observed. Plasma renin activity, angiotensin II, serum aldosterone, plasma noradrenaline, blood volume, and ouabain-sensitive erythrocyte sodium efflux rate constant did not differ between the three groups at baseline. A significant negative correlation was found between baseline sodium excretion and sodium efflux rate constant in subjects with positive family histories of hypertension. We conclude that the subjects with positive family histories of hypertension exhibit a blunted natriuretic and an exaggerated blood pressure response to an acute saline load as compared with the two control groups with negative family histories of hypertension. This could be of neuronal and/or hormonal origin. PMID- 1873012 TI - Left ventricular mass index and diastolic filling. Relation to blood pressure and demographic variables in a healthy biracial sample. AB - The relationships of left ventricular (LV) structure and diastolic filling to ambulatory blood pressure, race, age, and gender were studied in 104 young, generally healthy, untreated subjects with normal or marginally elevated blood pressure. Average daytime systolic blood pressure (r = 0.41, P less than .001), diastolic blood pressure (r = 0.38, P less than .001), male gender (r = 0.49, P less than .001), and age (r = 0.32, P less than .001) were univariate correlates of LV mass index as measured by M-mode echocardiography. In a stepwise multiple regression model, male gender, age, and systolic blood pressure were independent predictors of LV mass index. LV filling rate normalized to mitral stroke volume, a Doppler-derived index of diastolic filling, was inversely related to age (r = 0.47, P less than .001), heart rate (r = -0.27, P less than .01), LV mass index (r = -0.32, P less than .001), and diastolic blood pressure (r = -0.20, P less than .05). Age, heart rate, and LV mass index were predictors of normalized peak filling in a stepwise regression model. Race was not significantly related to either LV mass index or diastolic filling. Our results confirm the importance of demographic variables as well as blood pressure in determining LV mass and filling characteristics in humans prior to the development of sustained essential hypertension. These variables contribute to ventricular mass and diastolic function in varying degrees. Gender is strongly correlated with LV mass, but not with filling indices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873013 TI - Hypertensives' pressor response to norepinephrine. Analysis by infusion rate and plasma levels. AB - After 5 days of a 10 mEq sodium diet or 4 days of a 200 mEq sodium diet, 15 hypertensives and 11 normotensive control subjects received pressor doses of intravenous norepinephrine (NE). Analysis of pressor responses to the rate of NE infusion showed that the high salt diet sensitized subjects so that they needed less NE to raise systolic blood pressure (SBP) 20 mm Hg (P = .005). There was a complex interaction of salt intake, black race, and hypertension on NE pressor sensitivity (P = .03). Hypertensives attained lower plasma NE levels during the stepwise NE infusion, so we reanalyzed NE sensitivity in terms of the changes in plasma NE levels. This analysis also showed that during the high salt diet, subjects initiated a pressor response at lower plasma NE levels (P = .017) and raised SBP 20 mm Hg at lower NE levels (P = .007). The reanalysis showed that hypertensives initiated a pressor response at lower plasma NE levels (P = .03) and raised SBP 20 mm Hg at lower NE levels (P = .002). Plasma NE levels should provide a better guide to the concentration of NE at cardiovascular receptors than the rate of NE infusion. Analysis of pressor responses to plasma NE levels demonstrated that the hypertensives had an exaggerated pressor response to NE. PMID- 1873014 TI - Effects of dietary calcium on blood pressure, vascular reactivity and vascular smooth muscle calcium efflux rate in Zucker rats. AB - Previous data from this laboratory indicate that hypertension in insulin resistant Zucker obese rats is accompanied by an impairment in vascular smooth muscle Ca2+ efflux. Since insulin resistant states are also generally salt sensitive and dietary Ca2+ reduces blood pressure in some salt-sensitive states, we evaluated the effects of dietary Ca2+ on blood pressure and vascular reactivity and examined whether these effects are due to increased vascular smooth muscle Ca2+ efflux. We assigned 16 obese and 16 lean rats to a normal (0.5%) or high (1.5%) Ca2+ diet for 28 days, following which intraarterial blood pressure and in vitro vascular smooth muscle 45Ca efflux and vascular reactivity responses to phenylephrine and serotonin were measured. Blood pressure was elevated in the obese rats on both diets (P less than 0.2), and the high calcium diet lowered both systolic and diastolic pressure in both the lean and obese rats (P less than 0.5). Vascular reactivity was higher in the obese rats (P less than 0.2), but dietary Ca2+ exerted opposite effects on vascular reactivity to the agonists. High Ca2+ reduced sensitivity to serotonin in the obese rats by 54% (P less than .05) without affecting sensitivity in the lean rats. In contrast, the high Ca2+ diet increased sensitivity to phenylephrine by 31% in both groups (P less than .01). 45Ca efflux was lower in the obese rats compared to the lean rats (P less than .05), and the high Ca2+ diet increased this rate by 23% in the lean, but not the obese, rats (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873015 TI - Nonparallel effects of renin inhibitor treatment on plasma renin activity and angiotensins I and II in hypertensive subjects. An assay-related artifact. AB - Nonparallel effects of renin inhibitor treatment on plasma renin activity (PRA) and the plasma levels of angiotensins (ANG), as well as on blood pressure, have been observed in subjects with hypertension. This study addresses the possibility that renin inhibitors may show a high degree of plasma protein binding in vivo and that displacement of protein-bound inhibitor during the assay of PRA in vitro may lead to overestimation of renin inhibition. Indeed, with the ultrafiltration technique it was found that 96% of the novel renin inhibitor Ro 42-5892, when added to EDTA plasma, was bound to protein. The angiotensinase inhibitors phenylmethylsulfonyl fluoride (PMSF) and 8-hydroxy-quinoline sulfate (8-OHQ), which are currently used in PRA assays, caused a displacement of protein-bound inhibitor, thereby increasing its free concentration. This displacement was sufficient to explain the reduction in IC 50 of Ro 42-5892, which was seen in the PRA assay when PMSF and 8-OHQ were added to plasma. Such reductions in IC 50 were also seen with the renin inhibitors CGP 29-287, CGP 38-560A, and SR 43-845. When Ro 42-5892 was given, 1 mg/kg intravenously in 10 min, to subjects with hypertension, it appeared that plasma ANG I and II returned to baseline after 6-8 h, whereas PRA measured in the presence of PMSF and 8-OHQ was still suppressed. However, when PRA was measured without these angiotensinase inhibitors, the inhibition of PRA was parallel to the suppression of ANG I and II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873016 TI - Sugar-induced hypertension in Sprague-Dawley rats. AB - Male Sprague-Dawley rats were fed either conventional rat chow, or a diet in which vegetable starch was replaced with either glucose or sucrose for two weeks. At the end of this period, measurements were made of weight, blood pressure, and plasma glucose, insulin, and triglyceride concentrations. The average weight gain over the dietary period was approximately 75 g, and did not vary between the three groups. Mean (+/- SEM) blood pressure remained stable in the rats fed conventional chow (124 +/- 2 to 127 +/- 3 mm Hg), but increased significantly in rats fed the glucose-enriched diet (122 +/- 1 to 134 +/- 2 mm Hg, P less than .02, compared to chow-fed rats). The increase in blood pressure was even greater in rats fed the sucrose-enriched diet (122 +/- 2 to 144 +/- 2), and was significantly greater (P less than .005) than in rats fed either conventional chow or the glucose-enriched diet. Plasma glucose concentrations did not change in any of the groups, but plasma insulin concentration approximately doubled in rats fed either the glucose-enriched or sucrose-enriched diets. Finally, plasma triglyceride concentrations also were significantly higher (P less than .002) in both glucose-fed and sucrose-fed rats than in the control group. However, the increase was greatest in the sucrose-fed rats, and was significantly higher than in rats fed the glucose-enriched diet (P less than .002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873017 TI - Importance of chloride in the development of salt-induced angiotensin II hypertension in rats. AB - This study attempted to evaluate the effect of anion associated with sodium loading on the development of angiotensin II (AII)-induced hypertension in rats. Hypertension was induced by intraperitoneal infusion of AII(125 ng/min) for 12 days via miniosmotic pump (systolic blood pressure on day 12, 143 +/- 3 mm Hg). High dietary intake of sodium chloride significantly augmented the AII-induced hypertension (systolic blood pressure on day 12, 166 +/- 4 mm Hg), but equimolar sodium loading provided as sodium citrate failed to enhance AII hypertension (systolic blood pressure on day 12, 136 +/- 8 mm Hg). Thus, the data suggest that the full expression of salt (NaCl) sensitivity in AII hypertension depends on high dietary intake of both sodium and chloride. PMID- 1873018 TI - Plasma renin activity in renal transplant patients with hypertension. AB - Chronic renal allograft rejection (CR) is the major cause of graft loss after 1 year following transplantation. Hypertension (HTN) and proteinuria (Up) are the hallmarks of this immunologic allograft response. Over 1 year, 23 patients posttransplantation and with HTN (diastolic greater than 95 mm Hg) were examined. Serial serum creatinine (Scr), Up, urine creatinine (Ucr), and resting and enalapril challenged (EC) plasma renin activity (PRA) were all determined. Renal artery stenosis was excluded by noninvasive imaging. Of the 23 patients, eight eventually lost their renal allografts, while 15 maintained satisfactory renal function (Scr less than 2.5). Results of this study show that: 1) worsening renal function (RF) increases EC reactivity; 2) the presence of proteinuria is not itself related to increase in EC activity; 3) renin before and after EC was higher (P = .06) in the allograft loss group. In this study, patients with high PRA represent the highest EC responses. Therefore, they display not macrovascular lesions, but microvascular intrarenal disease; this defect is most likely secondary to chronic immunologic insult. PMID- 1873019 TI - Response to the cold pressor test in normotensive and hypertensive patients. AB - The response to the cold pressor test (CPT) was studied in 49 normotensive (NT) and 73 patients with essential sustained hypertension (HT). Patients were classified as responders when they increased their systolic pressure (SBP) by at least 16 mm Hg or their diastolic blood pressure (DBP) by at least 12 mm Hg. Forty-seven out of seventy-three (64%) increased their mean blood pressure (MBP) by 18.6 +/- 1.4 mm Hg (mean +/- SEM) in response to CPT. In NT subjects 23 out of 49 (47%) were responders (MBP = 16.3 +/- 1.3 mm Hg). In NT, but not in HT, patients, a negative relationship was observed between MBP changes during CPT and age (P less than .001) or basal DBP (P less than .01). There was no relationship between blood pressure response and the presence of a family history of hypertension. A positive correlation was found in HT patients between basal levels of active renin (AR) in the upright position and MBP changes during CPT (P less than .001). Mean plasma AR was 24.2 +/- 3.5 pg/mL in nonresponders v 37.5 +/ 2.9 pg/mL in responders (P less than .001). In HT, but not in NT, patients, blood pressure changes were associated with a simultaneous increase in HR (P less than .01 between delta MBP and delta HR). These results suggest that blood pressure elevation during CPT is a very common reaction in young normotensive subjects especially in those that have the lowest mean blood pressure. Therefore it is unlikely that CPT may be used as a predictor test of future hypertension in this population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873020 TI - Stability of ethnic differences in children's pressor responses during three annual examinations. AB - In this study, 395 healthy children had blood pressure and heart rate measured both at rest and during a stressful video game. Identical measurement procedures were used for three annual examinations. Consistently, black children demonstrated significantly greater pressor responses than white children. In view of the greater prevalence of hypertension among black adults than white adults, these data suggest that blacks exhibit hemodynamic irregularities well before the onset or diagnosis of hypertension. PMID- 1873021 TI - Association between disturbances in the immune system and hypertension. AB - For many decades evidence has been accumulating which implicates the immune system in the etiology and pathogenesis of hypertension. There appears to be a strong association between hypertension and immunologic dysfunction in humans and in rats. Patients with severe hypertension have significantly higher levels of serum IgG in comparison with normotensive controls. A positive correlation has been found between serum IgG levels and blood pressure in untreated essential hypertensive patients. In some studies it has been demonstrated that autoantibody levels are higher in both untreated and treated hypertensive patients than in normotensive control subjects. Furthermore, in the spontaneously hypertensive rat (SHR), several indices of immune system function have been shown to be depressed. There is also a significant correlation between immune intervention and antihypertensive effects. Short term administration of anti-rat thymocyte serum results in a significant decrease in the arterial pressure of the SHR. Chronic cyclophosphamide treatment prevents the progression of hypertension and significantly reduces its final level in the adult SHR. Neonatal thymic implants from normotensive donor rats delay the development of hypertension and significantly attenuate the level of the hypertensive state in the SHR. Also, thymectomy at an age of 4 weeks delays the development of hypertension in the SHR. The differences in the antihypertensive effectiveness of a variety of immunological manipulations in the SHR may be the result of their different levels of improvement on the severity of the autoimmune process in these rats. PMID- 1873022 TI - Reply to Vardan et al's "Importance of intraarterial blood pressure measurement in the evaluation of a new antihypertensive agent and the need to define hypertension also by this method". PMID- 1873023 TI - [Pharmacologic activity of 5-[(dialkylamino)alkyl]-8-chloro-3,5-dihydro-2 methyl/phenyl-4H-pyrido[ 2,3-b][1,4]-diazepine-4-ones]. AB - Some 5-[(dialkylamino)alkyl]-8-chloro-3,5-dihydro-2-methyl/phenyl-4H- pyrido[2,3 b] [1,4]-diazepin-4-ones previously prepared, were subjected to pharmacological experimentation in order to verify variation in biological activity induced by introduction of chlorine on the pyridine nucleus and by replacement of pyridinic with a benzenic ring. The effect upon mice with regard to exploratory activity, motor coordination, spontaneous activity, analgesic activity was tested and their anti-stricnine, anti-cardiazole, anti-amphetamine and anti-reserpine activities were also evaluated. The activities of the texted compounds were compared with those already showed by the analogues unchlorinated derivatives (B) and by isosters benzodiazepinones (D). PMID- 1873024 TI - The in vivo distribution of the 99mTc-labelled albumin and gelatin microspheres of a tuberculostatic agent, rifampicin. AB - The preparation of albumin and gelatin microspheres with a tuberculostatic agent, rifampicin, was studied, and its in vivo distribution was investigated by providing its accumulation in the target organ lungs. The purpose of the study is to improve the effectiveness by injecting the microspheres intravenously with much smaller doses than normally required with generalized systemic administration, whilst reducing the systemic side effects. The emulsion polymerization method is applied in microsphere preparation, and glutaraldehyde is employed for albumin and formaldehyde for gelatin microspheres as the cross linking agents. Biodistribution was determined by intravenous administration of particles of 25 to 27 microns 99mTc-labelled microspheres to Swiss albino mice. The radioactivity of the lungs was compared with the radioactivity of the liver, spleen, kidney, stomach and heart at 10, 30 and 60 min, and 6 and 24 h post injection. The percentage accumulated was higher in the lungs than in the other organs for both albumin and gelatin microspheres, whereas free rifampicin accumulated mainly in the liver. To support the data of the in vivo distribution studies, the microspheres were histopathologically investigated after the intravenous injection to Swiss albino mice. After the microscopic determination of the lungs and liver, the spherical microspheres were observed after 10,30 and 60 min, and 6 and 24 h post-injection. PMID- 1873025 TI - Mechanisms for diversity in gene expression patterns. AB - Despite the relatively low number of transcriptional regulatory proteins, the number of possible combinations that act in particular cell types at specific times and in response to appropriate extracellular stimuli is enormous. In considering the regulatory patterns of a particular gene, the critical determinants of diversity are the specific promoter sequences that govern the potential DNA-binding proteins which function either directly or indirectly in association with other proteins; constellations of proteins in the nucleus and their transcriptional activities; and synergistic or antagonistic protein-protein interactions. Although some of these regulatory principles operate in prokaryotes, the combinatorial nature of the transcriptional activation process, the existence of multiprotein families, and the prevalence of heteromeric protein complexes are characteristic of eukaryotic cells and are essential for the extraordinary complexity of gene expression patterns in multicellular organisms. PMID- 1873026 TI - Mechanisms of complex transcriptional regulation: implications for brain development. AB - The large number of transcription factors, their diverse sequence-specific interactions with DNA sites and with other transcription factors, and their ability to be modified in response to a variety of environmental cues and intracellular signals provide combinatorial codes for highly complex and yet highly organized patterns of gene expression likely to underlie the determination of diversity of neuronal phenotypes. Subtle differences in the combinations of transcription factors are likely to have profound consequences for cell phenotype, similar to the mechanism involved in the specification of cell types in yeast (reviewed in Herskowitz, 1989). Although our current understanding of transcriptional regulation in the brain comes largely from phenomenological studies, recent technical progress on two fronts promises a bright future. Homologous recombination technology in embryonic stem cells (reviewed in Capecchi, 1989; Rossant, 1990) allows the disruption of particular genes in transgenic mice and definition of the roles of identified transcription factors in mammalian neurogenesis. A second technological advance, targeted tumorigenesis, has provided neuronal model cell lines (Mellon et al., 1990; reviewed in Cepko, 1988; McKay et al., 1988) that mimic certain neuronal differentiation pathways. These combined genetic, cell biological, and biochemical approaches will greatly facilitate the study of neural development and function. PMID- 1873027 TI - DM-GRASP, a novel immunoglobulin superfamily axonal surface protein that supports neurite extension. AB - We have identified a 95 kd cell surface protein, DM-GRASP, that is expressed on a restricted population of axons. Its expression begins early in chick embryogenesis, and within the spinal cord it is localized to axons in the dorsal funiculus, midline floorplate cells, and motoneurons. Antibodies to DM-GRASP impair neurite extension on axons, and purified DM-GRASP supports neurite extension from chick sensory neurons. We have cloned and sequenced the cDNA corresponding to this protein and find that it is a new member of the immunoglobulin superfamily of adhesion molecules. Consequently we have named this protein DM-GRASP, since it is an immunoglobulin-like restricted axonal surface protein that is expressed in the dorsal funiculus and ventral midline of the chick spinal cord. PMID- 1873028 TI - Thrombospondin and a 140 kd fragment promote adhesion and neurite outgrowth from embryonic central and peripheral neurons and from PC12 cells. AB - The ability of thrombospondin (TSP), an extracellular matrix glycoprotein, and two proteolytic fragments to support adhesion and neurite outgrowth from embryonic dorsal root ganglia, spinal cord neurons, and PC12 cells was examined. Anti-TSP antibodies or a synthetic peptide (GRGDS) containing an RGD cell-binding region was also added to cells plated on TSP. TSP and its 140 kd fragment were more efficient than laminin controls in supporting adhesion. Neurites formed on laminin, on varying concentrations of TSP, and particularly the 140 kd fragment. The amino-terminal heparin-binding domain supported little adhesion and outgrowth. Both adhesion and process outgrowth on TSP were inhibited by addition of anti-TSP antibodies, but not GRGDS. PMID- 1873029 TI - Ca(2+)-activated K+ currents underlying the afterhyperpolarization in guinea pig vagal neurons: a role for Ca(2+)-activated Ca2+ release. AB - We examined the possibility that Ca2+ released from intracellular stores could activate K+ currents underlying the afterhyperpolarization (AHP) in neurons. In neurons of the dorsal motor nucleus of the vagus, the current underlying the AHP had two components: a rapidly decaying component that was maximal following the action potential (GkCa,1) and a slower component that had a distinct rising phase (GkCa,2). Both components required influx of extracellular Ca2+ for their activation, and neither was blocked by extracellular TEA (10 mM). GkCa,1 was selectively blocked by apamin, whereas GkCa,2 was selectively reduced by noradrenaline. The time course of GkCa,2 was markedly temperature sensitive. GkCa,2 was selectively blocked by application of ryanodine or sodium dantrolene, or by loading cells with ruthenium red. These results suggest that influx of Ca2+ directly gates one class of K+ channels and leads to release of Ca2+ from intracellular stores, which activates a different class of K+ channel. PMID- 1873030 TI - Detection of brain-derived neurotrophic factor-like activity in fibroblasts and Schwann cells: inhibition by antibodies to NGF. AB - mRNA coding for brain-derived neurotrophic factor (BDNF) has been detected in cultured L929 fibroblasts, rat dermal fibroblasts, and sciatic nerve Schwann cells, as well as in rat skin. Medium conditioned by cultured fibroblasts and Schwann cells also stimulates neurite growth from retinal explants and promotes the survival in culture of BDNF-responsive sensory neurons; biological activity is abolished by antibodies raised against NGF. These results suggest that molecules with BDNF-like activity may be produced by cells in the peripheral nervous system and that the BDNF-like activity in fibroblasts and Schwann cells is derived from molecules immunologically related to NGF. In support of this concept, antibodies against NGF have been found to reduce the biological activity of recombinant BDNF in culture and to cross-react with BDNF on Western blots. PMID- 1873031 TI - Elimination of a brain tract increases errors in pathfinding by follower growth cones in the zebrafish embryo. AB - The early zebrafish brain contains a simple axon scaffold of longitudinal tracts connected by commissures. Neurons in the nucleus of the posterior commissure (nuc PC) project growth cones along a specific route in this axonal scaffold, raising the possibility that specific axons in the early scaffold guide nuc PC growth cones. We tested this possibility by analyzing the behavior of nuc PC growth cones in embryos in which a portion of the scaffold, normally traversed by nuc PC growth cones, was surgically prevented from forming. Under these conditions nuc PC growth cones extended along both normal and aberrant pathways. This suggests that specific axons do provide guidance cues, since their removal leads to errors. However, these cues are not obligatory, since some growth cones still followed normal pathways. PMID- 1873032 TI - Hydrophobic substitution mutations in the S4 sequence alter voltage-dependent gating in Shaker K+ channels. AB - Voltage-activated Na+, Ca2+, and K+ channels contain a common motif, the S4 sequence, characterized by a basic residue at every third position interspersed mainly with hydrophobic residues. The S4 sequence is proposed to function as the voltage sensor and to move in response to membrane depolarization, triggering conformational changes that open the channel. This hypothesis has been tested in previous studies which revealed that mutations of the S4 basic residues often shift the curve of voltage dependence of activation along the voltage axis. We find that comparable or larger shifts are caused by conservative substitutions of hydrophobic residues in the S4 sequence of the Shaker K+ channel. We suggest that the S4 structure plays an essential role in determining the relative stabilities of the closed and open states of the channel. PMID- 1873033 TI - The growth inhibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallothionein-like protein. AB - We have purified and characterized the growth inhibitory factor (GIF) that is abundant in the normal human brain, but greatly reduced in the Alzheimer's disease (AD) brain. GIF inhibited survival and neurite formation of cortical neurons in vitro. Purified GIF is a 68 amino acid small protein, and its amino acid sequence is 70% identical to that of human metallothionein II with a 1 amino acid insert and a unique 6 amino acid insert in the NH2-terminal and the COOH terminal portions, respectively. The antibodies to the unique sequence of GIF revealed a distinct subset of astrocytes in the gray matter that appears to be closely associated with neuronal perikarya and dendrites. In the AD cortex, the number of GIF-positive astrocytes was drastically reduced, suggesting that GIF is down-regulated in the subset of astrocytes during AD. PMID- 1873034 TI - One stage repair of aortic arch anomalies and intracardiac defects. AB - Between August 1985 and May 1990, 27 neonates and infants underwent combined correction of intracardiac and aortic arch anomalies through a median sternotomy. Coarctation (CoA) was combined with VSD (6), AVSD (2), Taussig-Bing (TB) heart (5), transposition of the great arteries (TGA) (1), TGA + VSD (2), congenitally corrected TGA + VSD (1) and VSD + myxoid stenotic outlet valves (1). Interrupted aortic arch (IAA) was combined with VSD (10) and TB heart (1). Two patients had IAA type B as well as CoA. Age at operation varied from 2 to 243 days with a mean age of 51 days. Twenty patients (70%) were younger than 30 days. One TGA + VSD and all TB hearts had maligned outlet septum and right ventricular outflow tract obstruction (RVOTO). Posterior outlet septum deviation and left ventricular outflow tract obstruction (LVOTO) occurred in 8 patients with malalignment VSD and IAA (7) or CoA (1). Aortic arch reconstruction was performed using extended end-to-end anastomoses. In 3 patients, arch hypoplasia necessitated patch implantation. VSDs were closed through the right atrium unless the anatomy dictated otherwise. One TB heart was reconstructed with a Kawashima procedure. All other TB hearts and all TGAs were corrected with arterial switch operation. Obstructing outlet septum was resected whenever necessary. Follow-up was complete and included echo-Doppler control. Eleven patients had postoperative heart catheterisation. Early mortality was 18.5% (5 patients). Persisting LVOTO or RVOTO was responsible. There was no late mortality. Five patients were reoperated upon: 3 for stenotic anastomoses and 2 for a subaortic membranous stenosis. Successful balloon dilatation of recoarctation was performed four times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873035 TI - Optimal exposure of the mitral valve through an extended vertical transeptal approach. AB - The mitral valve was approached through a vertical transeptal incision extended into the roof of the left atrium in 111 patients. Good exposure was invariably provided even in unfavorable situations such as a small left atrium combined with right ventricular hypertrophy or a previously implanted aortic prosthesis. The only hospital death in the entire series was not related to this approach to the mitral valve. Due to breakage of the suture in the roof of the left atrium and to incomplete reconstruction of the atrial septum resulting in a large left-to-right shunt, 2 patients required reinstitution of cardiopulmonary bypass. Both had a smooth postoperative course. Other intra- or postoperative complications related to the incision did not occur. Duration of cardiopulmonary bypass and aortic occlusion was not significantly different from that of patients operated upon through the conventional left atrial approach in the year preceding the experience embraced by this study. Only 3 of 52 patients who were preoperatively in sinus rhythm were discharged in atrial fibrillation. Enhanced atrial vulnerability was demonstrated preoperatively in all 3. These data support a wide application of the extended vertical transeptal approach in mitral valve surgery. PMID- 1873036 TI - Coumarin anticoagulation during pregnancy in patients with mechanical valve prostheses. AB - Between January 1987 and December 1989, 20 female patients with one mechanical valve prosthesis (MVP) for at least 1 year postoperatively were studied while on coumarin therapy for the full length of pregnancy. In each case, caesarean section was scheduled for the 38th week. Patients were selected according to the following criteria: (1) prothrombin ratios remaining within the therapeutic range for more than 85% of their total estimations in the previous 12 months with mean daily doses of warfarin less than 5 mg; (2) stable cardiac status; (3) no previous obstetric diseases and (4) full acceptance of the risks involved in the protocol. The patients were in NYHA functional class I or II. Their ages ranged from 23 to 31 years (mean 26 +/- 3). Ten patients had a mitral prosthesis and 10 an aortic prosthesis. Among the 20 mechanical valve prostheses, 10 were Sorin, 6 Starr-Edwards, 2 Bjork-Shiley, and 2 Lillehei-Kaster. Eighteen patients were in sinus rythm, 1 in chronic atrial fibrillation, and 1 had a permanent endocardial pacemaker. Nineteen were delivered by caesarean section: warfarin was withdrawn 48 h before surgery and resumed 24 h thereafter. One patient had premature spontaneous delivery at 36 weeks. The mean prothrombin ratio measured weekly in the 20 patients was 2.06 +/- 0.45 INR, using a mean daily warfarin dose of 4.1 mg +/- 1.63. The mean value of the prothrombin ratio during caesarean section for the 19 patients was 1.23 +/- 0.38 INR. In the 20 live births, the mean birth weight was 2.9 kg +/- 0.40.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873037 TI - Right ventricular dynamic cardiomyoplasty: an experimental model. AB - The effectiveness of dynamic cardiomyoplasty as a means of haemodynamic support in heart failure remains controversial. We have undertaken a study of right ventricular dynamic cardiomyoplasty in sheep using intravenous propranolol to provoke heart failure. Muscle conditioning was performed with cardiomyostimulators following a previously established protocol. We performed multiple invasive measurements of haemodynamic parameters including arterial blood pressure, cardiac output, pulmonary artery capillary wedge pressure, right ventricular dp/dt and end diastolic pressures. These were performed before induction of heart failure, after induction of heart failure, and with pacing of the cardiomyoplasty flap in established heart failure. Our results confirm that we were able to establish significant heart failure and that subsequent pacing of the conditioned muscle flap was able to return cardiac output and right ventricular function to their pre-failure control levels. PMID- 1873038 TI - Implantable cardioverter/defibrillators (ICD): a new lead-system using transvenous-subcutaneous approach in patients with prior cardiac surgery. AB - The current approach in cardioverter-defibrillator implantation requires placement of epicardial leads which may lead to pericardial and/or pleural effusion and pneumonia during the perioperative period. Although ICD implantation is less invasive than other surgical techniques for the treatment of rhythm disturbances, the perioperative mortality must be considered. Minimizing the operative procedure could lead to a reduction in perioperative mortality. Therefore, we investigated an approach without the need for thoracotomy using a transvenous/subcutaneous lead system. In nine patients with prior cardiac surgery, defibrillator implantation was performed by a transvenous/subcutaneous approach. There was no perioperative mortality. In all patients, a sufficient defibrillation threshold was achieved. The defibrillation pulses were delivered as two sequential pulses between a right ventricular electrode (cathode) and a coronary sinus or superior caval vein electrode (anode 1) and a subcutaneous patch electrode (anode 2). Intubation of the coronary sinus was necessary in 4 patients in order to obtain satisfactory defibrillation thresholds. These data demonstrate that a transvenous/subcutaneous approach is feasible in patients with prior cardiac surgery obviating the need for thoracotomy. Sensing function of the RV-electrode, intubation of the coronary sinus and the intraoperative use of an epicutaneous patch electrode are current problems of this new technique. PMID- 1873039 TI - Actuarial survival and other events following valve surgery in octogenarians: comparison with an age-, sex-, and race-matched population. AB - From January 1973 to December 1989, 54 patients over 80 years of age underwent an intracardiac repair which included a cardiac valve operation. There were 21 males and 33 females. Mean age at operation was 82 years, range 80-89 years. Fifty-two patients (96%) were in New York Heart Association functional class III or IV preoperatively. Six patients had undergone previous valve surgery (11%). There were eight hospital deaths (14.8%). Risk factors for hospital death included older age at repair (p = 0.008), increased total cardiopulmonary bypass time (p = 0.06), and, possibly, smaller aortic valve prosthesis (p = 0.10). All 46 hospital survivors were followed up at a mean of 28.8 months after hospital discharge. There were 11 late deaths (23.9%), occurring at a mean of 32.3 months postoperatively. Survival analysis indicated that increased age (p = 0.06) and increased pulmonary artery diastolic pressure preoperatively (p less than 0.07) were multivariate risk factors for overall mortality. Actuarial survival at 5 years was 44%, with no difference from survival in an age-, sex-, and race matched population. We conclude that octogenarians in the modern era have good chance for survival following valvular surgery. As hazards for full anticoagulation were low in this series, if valve repair is not feasible, we presently recommend the use of mechanical valves in the elderly to reduce the requirement for late reoperation due to bioprosthesis degeneration. PMID- 1873040 TI - PTCA of the left main stem following protective coronary artery bypass grafting. AB - Percutaneous transluminal coronary angioplasty (PTCA) was performed in 14 patients with significant left main stem stenosis following protective coronary artery bypass grafting (CABG). The procedure was successful in 13/14 patients (93%), achieving a decrease in mean diameter stenosis from 74% +/- 7% to 31% +/- 12% (P less than 0.01). Accordingly, the absolute stenosis diameter increased from 0.9 mm +/- 0.3 mm to 2.4 mm +/- 0.5 mm (P less than 0.01). Dissection of the left main stem artery and a transient significant fall of blood pressure each occurred in one patient. No other serious complications were noted. Eight of 13 patients (62%) with successful PTCA underwent control angiography. Restenosis had occurred in 3 of 8 patients (38%) with total occlusion of the left main stem in 1 patient. All bypass grafts were found to be patent at follow-up. Clinical evaluation in all 14 patients revealed no serious events (death, myocardial infarction, repeat revascularization procedure) during a mean follow-up period of 27 months (range 6-39 months). PTCA of the left main stem following CABG can be considered a relatively safe and effective procedure with a marked restenosis rate but beyond that, an uncomplicated long-term follow-up. PMID- 1873041 TI - Mechanical left ventricular support as a bridge to cardiac transplantation in childhood. AB - The mechanical extrathoracic "Berlin Heart" cardiac assist device was used for left ventricular support in an 8-year-old child of 27 kg body weight. Terminal left ventricular failure and life-threatening ventricular tachyarrhythmias in this child were sequelae of coarctation of the aorta, aortic stenosis and resultant severe left ventricular dilatation, hypokinesia and fibrosis. With the assist device, cardiogenic shock could be reversed. The child was extubated and mobilized during an 8-day waiting period for orthotopic heart transplantation. This case illustrates that the use of ventricular assist devices can be successfully extended to children and may be advantageous compared to other techniques of mechanical circulatory support, such as balloon pumping or extracorporeal membrane oxygenation. PMID- 1873042 TI - Simultaneous pneumonectomy and esophagectomy for bronchial carcinoma. AB - Two cases of bronchial carcinoma with oesophageal involvement are presented. Both were treated by simultaneous pneumonectomy and oesophagectomy. The postoperative course of each patient was complicated by secondary infection of the pneumonectomy space. One patient expired from a recurrent intratracheal tumour on the 83rd postoperative day and the other remains tumour free 3 years after treatment. As few therapeutic alternatives exist for non small cell bronchial carcinoma, primary radical surgical treatment should be considered, even in advanced cases where the tumour invades the oesophagus. PMID- 1873043 TI - [Anticoagulation and valvular heart disease]. PMID- 1873044 TI - [Epidemiology and clinical evolutionary aspects of multiple sclerosis in Navarra]. AB - In the present study 84 patients with the diagnosis of multiple sclerosis were identified as living in Navarra on the date of prevalence (December 31, 1986). The raw yearly incidence rate was 0.49/100000, which is similar to that in Mediterranean countries. A significant increase of this rate was found between 1951 and 1986, which was interpreted as a consequence of higher economic status and/or progressive industrialization. The raw prevalence rate was 16.4/100000 and age-specific prevalence was 26.5. Therefore, Navarra is a medium risk area for MS. Mean age at onset was 29.3 years, with a significant female predominance. In addition, MS presented earlier in females. The relationship between MS and latitude of the residence area was confirmed. The most common presenting symptoms were motor (paresia) and sensory (paresthesia). Cerebrospinal fluid was abnormal in 86.5% of patients, evoked potentials (mostly visual) in 85.9%, and magnetic resonance in 100%. Demyelinizing signs were detected with CT in 29.4% of patients. The diagnostic criteria of the Boston University Workshop were highly reliable. The most common evolutive pattern was the pure remitting one. The mean degree of disability was 3.6 in Kurtzke's scale. The evolutive form and the duration of the disease were identified as predictive of disability. 43.5% of benign forms and 13.1% of late onset forms were identified. PMID- 1873045 TI - [Cellular transplants for Parkinson's disease]. AB - In rats with a lesion of the dopaminergic nigrostriatal pathway induced by 6 hydroxydopamine (6-OHDA), the histologic and functional viability of the striatal implant of fetal mesencephalic substantia nigra has been demonstrated. In the same model, the implant of adrenal medulla is also effective but less lasting. In monkeys with parkinsonism induced by MPTP there are suggestions of effectiveness of the fetal mesencephalic implant and also of other tissues such as placenta and sympathetic ganglion or sural nerve. Now the possibility of a better functional recovery by acting on the neuronal growth factors is being evaluated. In patients with Parkinson's disease, the accumulated experience indicates that 32% are improved with adrenal medulla implant, but the best candidates are those who also benefit from the available drug therapy without the risks of surgery. The implant of fetal tissue has been carried out in about 90 patients, with very variable results. In the most thoroughly investigated patients the improvement has been moderate. The future research points to the identification of the factors that control and regulate striatal reinnervation and the use of genetically determined cells. That would permit a more precise reposition of the biochemical deficiency in Parkinson's disease, without the ethical and practical problems derived from the use of fetal tissue. PMID- 1873046 TI - [The centenary of lumbar puncture]. PMID- 1873047 TI - [Dysphagia as the sole manifestation of Arnold-Chiari malformation in adults]. PMID- 1873048 TI - [Internuclear ophthalmoplegia in giant cell arteritis]. PMID- 1873049 TI - [Ante mortem diagnosis of Marchiafava-Bignani disease. Chronic demyelinating form]. PMID- 1873050 TI - [Mortality patterns of children with epilepsies in a children's medical center]. AB - Two hundred and thirty-seven children have died who were seen in the Division of Neurology, Kanagawa Children's Medical Center from 1975 to 1989. They corresponded to about 11% of the total death in the hospital. A total of 128 cases of 237 deaths (54.0%) were suffering from epilepsies, most of whom were also complicated with other CNS disorders. The causes of death were pneumonia, respiratory failure and suffocation in 60%, whereas status epilepticus or convulsions only in 14%. About 40% of victims died at home or in an emergency room without effective resuscitation. Mortality was considered high in infantile spasms (16 out of 146, 11%) and in severe myoclonic epilepsy in infancy (4 out of 8, 50%). It was note worthy that 3 cases of severe myoclonic epilepsy in infancy died of status epilepticus and 2 died at home. Sixteen cases whose chief problems were partial epilepsies and severe myoclonic epilepsy in infancy, died of status epilepticus in 10 cases, convulsions after tonsillectomy, etc. Causes of death of these 16 cases were related to convulsions except in two cases whose causes were pneumonia in one and unknown in the other. About a half of them (7 cases) died at home. Adequate managements appeared necessary to prevent accidental deaths of children with epilepsies. PMID- 1873051 TI - [Myelination in very low birth weight infants--evaluation by MRI]. AB - The prognostic significance of cerebral myelination was evaluated with magnetic resonance imaging (MRI) in very low birth weight infants. Myelination was graded in two specified sites, optic radiation and corpus callosum, based on the stages of normal term babies and healthy premature infants. The subjects were 30 preterm infants weighing less than 1,500 gm at birth. MRI was performed at 4 to 7 months (corrected age). The normal myelination stage was seen in 18 cases, while a delayed stage was noticed in 12 cases. In the normal myelination group, only 1 case (6%) had handicaps. In the delayed myelination group, 8 cases (67%) had handicaps. Our results showed that delayed myelination was closely related to a poor prognosis. We believe that MRI would be a very good imaging modality for predicting the outcome of very low birth weight infants, particularly in terms of evaluation of myelination. PMID- 1873052 TI - [The comparison of motor developmental processes between spastic diplegic children and athetotic children who have been treated since infancy]. AB - We studied the correlation between motor developmental processes and prognosis of locomotion at the age of 4 years, among 15 spastic diplegic children (S) and 21 athetotic children (A), who started treatment under 1 year of age. The children of each type were divided into two groups according to the ability of locomotion at the age of 4 years; S- I: 6 walkers, S- II: 9 crawler, A- I: 11 walkers and A- II: 10 crawler. We compared the average corrected ages when the subjects attained the abilities to roll over, creep, sit with hands, crawl, sit up, cruise with support, stand up, and walk alone, and made a statistical analysis by t test among 4 groups. Also we compared the cumulative frequency percentages for the ages about the locomotion mentioned above. The S- I group attained all of the abilities of locomotion significantly earlier than the S- II group. The A- I group could crawl and sit up significantly earlier than the S- II group. The A- I group could crawl and sit up significantly earlier than the A- II group. The S- I group began to creep and sit with hands significantly earlier than the A- I group. We found no significant differences between the S- II group and the A- II group in motor developmental processes. These studies revealed that it would be possible to expect the prognosis of ambulation at the age of 4 years according to the early motor developmental processes among the spastic diplegic children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873053 TI - [The relation between one-sided occipital flattening and laterality of rolling over]. AB - The rolling-over of the body is one of the developmental mile-stones. Several infants have the laterality of rolling-over in early state and the dominant side in later state. The abilateral occipital flattening is thought to be caused by head positioning in the neonatal period and early infancy. Asymmetrical development of rolling-over was studied in relation with head positioning, relating skull occipital flattening. We examined 2919 infants aged 7 months with the questionnaire about the side of skull occipital flattening and the initial turning side of rolling-over. 1975 infants had the dominant side of rolling-over; the left side 45.4%, and the right side 47.7%. 761 infants had one-sided occipital flattening; left-side 41.3%, and right-side 54.8%, 520 infants had dominant-sided rolling-over accompanied with one-sided occipital flattening. The positive relationship between the side of rolling-over and the side of occipital flattening could not be proved by chi-square statistical analysis. These findings suggest that laterality of rolling-over, one of asymmetrical motor developments is not related to the head positioning in early infancy. PMID- 1873054 TI - [Sequential MRI in two cases with periventricular leukomalacia]. AB - We investigated two children with cystic periventricular leukomalacia, which we had detected by ultrasonography (US) during the neonatal period, with magnetic resonance imaging (MRI) of the brain at 4, 9, and 15 or 19 corrected months of age. Both inversion-recovery (IR) and T2-weighted spin-echo (SE) sequences were used for this study. We observed cysts involving the periventricular white matter at the region adjacent to bilateral frontal horns in case 1 and adjacent to the posterior horns of the lateral ventricles in case 2. MRI at 4 months showed the irregularity of the ventricular wall and delayed myelination, compared to that of an age-matched control. The T2-weighted SE and IR imaging at 9 months demonstrated abnormally increased signal in the white matter. These findings were more evident at the 3rd MRI examination. The location of end-stage periventricular leukomalacia lesions were consistent with the distribution of cystic lesions seen on US. MRI at sagittal sections was useful for the detection of main periventricular leukomalacia lesions. A possibility exists that MRI might be useful in detecting subtle lesions of periventricular leukomalacia in which we cannot find by US. PMID- 1873055 TI - [Four cases of Cockayne syndrome]. AB - The evaluation of four patients with Cockayne syndrome (CS) by computed tomography (CT) and magnetic resonance imaging (MRI) is reported. All patients had characteristic clinical manifestations of CS. In a special respect, we found hyperopia in two patients and previous habitual abortions in two maternal histories. Extrapyramidal signs were seen in one patient. Three patients are type 1 CS (case 1, 3, 4) and one patient (case 2) is type 2 CS (congenital form). The cranial CT in two patients (case 1, 2) revealed prominent calcifications in basal ganglia, dentate nucleus and hemispheric white matter. While CT showed vagal calcifications in basal ganglia in other two patients (case 3, 4), T2-weighted MRI revealed obvious low intensity area in putamen and caudate nucleus, and high intensity area in the white matter. Sagittal section revealed atrophic changes of cerebellar vermis and brain stem. Thus it seems that MRI may be useful diagnostic adjunct in CS patients. PMID- 1873056 TI - [A two-year-old clinically manifesting carrier of Duchenne muscular dystrophy]. AB - A two-year-old symptomatic carrier of Duchenne muscular dystrophy (DMD) confirmed by dystrophin immunohistochemical study was reported. She had mild proximal muscular weakness and elevated serum creatine kinase (CK) level. There were no family members of DMD. CT examination revealed low density areas in the muscles similar to that seen in the early stage of DMD. Biopsied specimen of muscle showed myopathic changes with necrotic and regenerating fibers. The immunohistochemical study using an antiserum against dystrophin showed the mosaic expression of the surface membrane, with positive and negative patches. Accordingly, she was strongly suggested to be a DMD carrier. This case shows that dystrophin immunohistochemistry is useful for diagnosis of a DMD carrier without affected family members. PMID- 1873057 TI - [Hypothalamic GH Deficiency and gelastic seizures in a 10-year-old girl with MELAS]. AB - A case of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes, in which a pituitary growth hormone (GH) secretion deficiency of hypothalamic origin was revealed through neuro-endocrinological examinations, was described. The case was a 10-year-old girl, who had been suffering from generalized tonic seizures since age 5, four episodes of alternating hemiplegia since age 6, stunted growth since age 7, and simple partial motor seizures as well as gelastic seizures since age 8. Marked elevation of lactate and pyruvate in both serum and CSF, abundant ragged red fibers in biopsied muscle, and low density areas in the left occipital lobe and bilateral globus pallidus in addition to diffuse brain atrophy on CT scan and MRI of the head were demonstrated, although the activities of muscle enzymes complex I-IV were within normal ranges. Pituitary GH secretion was deficient under the loadings with insulin, L-DOPA, sleep, and a single growth hormone releasing factor (GRF) administration, but normal GH response was registered under the repetitive stimulation with GRF. Activities of other hormonal axes were normal. It is likely that short stature commonly observed in MELAS patients is due to hypothalamic dysfunction, which might be brought out by chronic ischemia and energy deficiency of the diencephalon based upon mitochondrial abnormality of that region. It is likely that gelastic seizure in this case is due to hypothalamic dysfunction. PMID- 1873058 TI - [Diagnosis of abortive form of Sturge-Weber syndrome by Gd-DTPA MRI]. PMID- 1873059 TI - [Onset period and prognosis of epilepsy in patients with perinatal or early infantile brain damage]. PMID- 1873060 TI - [Adrenoleukodystrophy with high signal intensity areas in the pyramidal tract from internal capsule to the brain stem and spinal cord in MRI (long TR)]. PMID- 1873061 TI - [Efficacy and problem in performing PET study using 15O2 steady state inhalational technique in children]. PMID- 1873062 TI - Total etch--the rational dentin bonding protocol. AB - Phosphoric acid etching of dentin is critically reexamined in view of current adhesive resin development. Research and clinical experience both suggest that "total etch," the simultaneous etching of dentin and enamel, is a rational protocol with many modern adhesive resins. PMID- 1873063 TI - Evaluation of a 4-META porcelain repair system. AB - A recently introduced porcelain repair system utilizing 4-META (Etch-Free Primer with C & B-Metabond) was evaluated for bond strength to porcelain. This system purportedly eliminates hydrofluoric acid-etching and silane pretreatment. Forty porcelain specimens were prepared and treated with the 4-META repair system. A resin cylinder was bonded to the treated porcelain surface. Twenty of the specimens were tested after 24 hours while the other 20 were tested after thermocycling (800 cycles at 6 degrees C to 60 degrees C). The mean bond strengths were: 24 hours 17.4 MPa (+/- 4.8), thermocycled 19.1 MPa (+/- 7). Cohesive failure of the porcelain occurred in all of the specimens, both the 24 hour and the thermocycled. These bond strengths compare favorably with or exceed those of other porcelain repair systems tested in other studies. PMID- 1873064 TI - Abfractions: a new classification of hard tissue lesions of teeth. AB - Due to the stresses resulting from biomechanical loading forces exerted on the teeth (static, as in swallowing and clenching or cyclic, as in chewing), both enamel and dentin can chip or break away. This loss of tooth substance, which shall be termed Abfraction, is dependent on the magnitude, duration, direction, frequency, and location of the forces. These abfractive lesions are caused by flexure and ultimate material fatigue of susceptible teeth at locations away from the point of loading. Clinical observation of a variety of enamel and dentin lesions due to the shapes, sizes, loci, and frequency warrants a new and distinct classification. PMID- 1873065 TI - Effect of two cavity designs on root surface marginal microleakage. AB - Current methods for bonding composite resins rely upon the etching of enamel to attain a bond that is strong enough to resist polymerization shrinkage and decrease the amount of marginal microleakage. Previously, modification of cavity designs have been evaluated that have enhanced retention. However, all these cavity designs have utilized methods to increase the surface area of enamel to bond thus resulting in a stronger enamel bond. This in vitro study evaluated the effect of one cavity design modification when the restoration is placed entirely on cemental surfaces and relied on only cementum and dentin. PMID- 1873066 TI - Clinical technique for an in-office porcelain modification. AB - All porcelain restorations, especially intra- and extracoronal restorations, have become an accepted treatment modality for the esthetic restoration of posterior teeth. One problem with these restorations is the limited ability to modify the porcelain when a proximal contact is not present or there is an open margin. Using a low-fusing porcelain in a glazing oven, practitioners can easily accomplish such modifications during the try-in and cementation appointment for porcelain inlays. This technique eliminates the need for returning the porcelain inlay to the laboratory for modification and a second patient visit to complete the restoration. This paper describes an in-office procedure for modifying porcelain restorations and a scanning electron micrographic evaluation of the etched porcelain surface after using this modification technique. PMID- 1873067 TI - Creating the appearance of white enamel dysmineralization with bonded resins. AB - In special cases, white enamel discoloration can be stimulated using bonded resin materials. This paper describes a method of using bright white visible light polymerized resin sealant material as an enamel bonding agent, which is overlayed with composite resin to enhance wear resistance of the restoration. PMID- 1873068 TI - Esthetic improvement of "white spot" enamel stains. PMID- 1873069 TI - Smooth surface glass ionomer restoration for primary teeth. AB - Glass ionomer restorative cement offers the clinician an alternative to bonded composite resin for restoration of certain lesions in primary teeth. This article details a step-by-step procedure for restoration of a smooth surface carious lesion in a primary incisor using an encapsulated glass ionomer restorative material and reviews advantages and limitations of the cement. A light-hardened glass ionomer liner/base that has proven useful as an enamel and dentin restorative is also described. PMID- 1873070 TI - Evaluation of a 4-META adhesive cement. AB - This study investigated the shear bond strength of a new 4-META adhesive cement (C & B-Metabond) to dentin and Ni-Cr-Be alloy (Rexillium III). Fifteen human molar teeth had dentin bonding sites prepared by grinding away the enamel on a water-cooled abrasive wheel to a 600 grit. Fifteen metal alloy specimens were cast, ground to a 600 grit, and air abraded with 50 micron alumina. The 4-META cement was applied to the dentin and metal in accordance with the manufacturer's instructions. After 24 hours in water at 37 degrees C, the shear bond strengths were recorded. The mean bond strength to dentin and the metal alloy was 20.1 megapascals. PMID- 1873071 TI - Ultrastructural characteristics of lymphokine-activated killer cells of the rat in comparison with natural killer cells. AB - Lymphokine-activated killer (LAK) cells with a broad spectrum of tumor cell killing have been reported to be related to natural killer (NK) cells morphologically and phenotypically. We here examine the ultrastructural characteristics of LAK cells of the rat, comparing them to those of normal and OK 432-activated NK cells. Results show that, five days after the culturing of spleen lymphocytes with human recombinant interleukin-2, there were induced LAK cells, which were large granular lymphocytes and had a cytotoxic capacity against NK-resistant P-815 tumor cells. They were larger in size than NK cells and richer in cell organelles such as ribosomes, rough endoplasmic reticulum, a Golgi apparatus, granules and vesicles. The granules of LAK cells were shown to be related to multivesicular bodies as those of NK cells; they included multivesicular bodies, fully dense granules and intermediate forms between them. The average numbers and sizes of the granules and the proportion of multivesicular bodies and intermediate forms among the total granules were greater in LAK cells than in NK cells. The density of the small vesicles packed in multivesicular bodies and intermediate forms was much higher in LAK cells. At the contacting surface of the LAK cells bound to the target cells, exocytosis of multivesicular bodies was shown to occur. We recognized here two populations of LAK cells with different types of vesicles, one containing rod-cored vesicles and the other a new type of vesicles termed "demilune-cored vesicles". The latter vesicles were the same in size as the rod-cored ones and contained a dense core located eccentrically. Between these two populations of LAK cells, there was no difference concerning the profile of the dense granules. The present study indicates that, although LAK and NK cells share several ultrastructural features, the former show markedly enriched cell organelles, which indicate an accelerated metabolism of the cell for continuous proliferation. PMID- 1873072 TI - Three-dimensional organization of the collagen fibrillar framework in the rat adrenal gland. AB - The three-dimensional organization of the collagen fibrillar framework in the rat adrenal gland was studied using an alkali-water maceration method and scanning electron microscopy. The structure thus obtained was a continuum of collagen fibril plexuses extending through the adrenal capsule, cortex and medulla. The capsule consisted of finely meshed collagen fibril sheaths and layered, coarsely meshed plexuses of bundles of collagen fibrils. In the cortex, the channels of cortical capillaries were surrounded by thin sheaths of collagen fibrils. Many slender bundles of collagen fibrils extended from these sheaths into intercellular spaces and interconnected adjacent pericapillary sheaths. The collagen fibril sheath tubes precisely reflected the cortical blood vascular architecture; thus the three cortical zones--zona glomerulosa, zona fasciculata and zona reticularis--were also clearly remarked. In the medulla, collagen fibrils were interwoven into more tightly meshed sheaths around the peripheral radicles and venous tributaries of the central veins. Basket-like collagen fibril sheaths divided the spaces among these tree-like perivascular collagen fibril sheath tubes into round compartments which, in intact tissues, contained chromaffin cell nodules and nervous elements. Small tube-like spaces for housing the medullary capillaries were located in the interstices of contiguous collagen fibril baskets. Besides supporting the organization of the gland, the collagen fibrillar framework in the adrenal gland is believed to play important roles in providing three-dimensionally elaborated extravascular spaces for the diffusion of metabolites and physiological messengers, including hormones. PMID- 1873073 TI - The ultrastructure of human cumulus-corona cells at the time of fertilization and early embryogenesis. A scanning and transmission electron microscopic study in an in vitro fertilization program. AB - We observed the ultrastructure of the cumulus-corona cells (CC cells) surrounding: 1) human preovulatory oocytes unfertilized after in vitro insemination and 2) in vitro-fertilized polypronuclear ova (PO) at the pronuclear stage (3 pronuclei) and during early cleavage, at the 3-8 cell stage (cleaving PO). All the samples were obtained from women who underwent pharmacological hormonal stimulation during in vitro-fertilization procedures. Both cell groups were composed of irregularly rounded CC cells, showing an oval nucleus with one or more reticular nucleoli. Spermatozoa in close contact with CC cells were also seen. Linear and annular gap junctions between neighbouring cells were present, particularly in Group 1. Lipid droplets were present in both groups, appearing slightly more numerous and electron-dense in Group 2. In Group 1, mitochondria were numerous, polymorphic, and provided with cristae varying from lamellar to tubular. In Group 2, mitochondria also showed polymorphism, with bacilliform organelles with tubular cristae being predominant. In both groups cisternae and associated vacuoles and vesicles belonging to the Golgi complex were scattered in the cytoplasm of CC cells. Similarly, tubular and vesicular profiles of smooth endoplasmic reticulum were abundant and uniformly distributed throughout the cytoplasm of CC cells of both groups. In contrast, the abundant rough endoplasmic reticulum in Group 1 was formed by parallel stacks of flattened cisternae, whereas it was less plentiful and not arranged in stacks in Group 2. The CC-cell surface appeared covered by numerous membrane expansions in both groups. The expansions in Group 1 were mainly composed of blebs of various sizes and a few short microvilli, whereas in Group 2 numerous microvilli covered the cell surface. These observations demonstrate that a gradual establishment and maintainance of a steroidosynthetic capability (luteinization) takes place in CC cells, particularly during and shortly after fertilization, as occurs contemporaneously in the granulosa cells of the postovulatory follicle. Our results may be considered as ultrastructural confirmation of the capability of the CC cells to produce small amounts of steroids (estrogens and mainly progesterone). These hormones, alone or together with other substances (proteins, nutrients, growth factors?), might--around the fertilization time--act positively upon the early embryo itself, as well as on the microenvironment in which the embryo develops, both in vivo and in vitro conditions. PMID- 1873074 TI - The ultrastructure of cartilage formation from neonatal skeletal muscle in vitro. AB - Histological changes in cultured neonatal skeletal muscle tissue at the early stage of cartilage induction by syngeneic insoluble bone matrix gelatin (BMG) containing bone morphogenetic protein were examined by light and electron microscopy. Minced skeletal muscle was cultured on hemicylindrical pieces of BMG for 14 days. Chondroblasts first appeared in the crevices of the BMG on Day 7 of the culture, and cartilage tissue was seen to fill the crevices completely by Day 10. The main findings in this work are as follows: 1) the activation of satellite cells and necrosis of myonuclei; 2) the migration of satellite cells from the basement membrane; 3) fibroblasts with increased numbers of organelles between degenerated muscle fibers closely resembling the migratory satellite cells; 4) the migration of the spindle-shaped cells into the crevices of the BMG; and 5) change of the spindle-shaped cells to chondroblasts. These findings suggest that neonatal skeletal muscles, which appear more mature than embryonic muscles, also have a chondrogenetic potential when grown on BMG, and that chondroblasts originate from the spindle-shaped cells which are thought to result from migratory satellite cells as well as fibroblasts. PMID- 1873075 TI - Localization of pyroantimonate-precipitable calcium in the vestibular organs of the rat and guinea pig. AB - Localization of pyroantimonate-precipitable calcium (Ca) was examined in the vestibular organs of the rat and the guinea pig. Precipitates were observed around the otoconia and in the otolithic membranes of the macula sacculi and macula utriculi. Although the deposition was heavier in the rat than in the guinea pig, the distribution of the Ca-pyroantimonate was similar in both species. Most otoconia in the dark cell area had precipitates around and inside the otoconia. Furthermore, there was some precipitation in the cupulae of the semicircular canals in both animals. The presence of Ca in the precipitates was confirmed by X-ray microanalysis and extraction with EGTA. Localization of the Ca pyroantimonate around the otoconia in these animals agrees with localization of precipitates of endolymphatic crystals in the tree frog, which are known to grow mainly by accretion. Thus, the otoconia of the rat, and probably also of the guinea pig, can be assumed to grow mainly by accretion. PMID- 1873076 TI - GABAergic neurons in the mouse superficial dorsal horn with special emphasis on their relation to primary afferent central terminals. AB - Immunocytochemical studies were carried out on the morphological relation between primary afferent central terminals (C-terminals) and GABAergic neurons in the mouse superficial dorsal horn. The superficial dorsal horn is composed of many synaptic glomeruli comprising two types: Type I with centrally located CI terminals surrounded by several dendrites and few axonal endings, and Type II with centrally located CII-terminals surrounded by several dendrites and a few axonal endings. The CI-terminals are sinuous or scalloped with densely packed agranular synaptic vesicles, a few granular synaptic vesicles and mitochondria, and show an electron dense axoplasm, whereas the CII-terminals are large and round or rectangular with evenly distributed agranular synaptic vesicles, a number of granular synaptic vesicles and mitochondria, and show an electron opaque axoplasm. The immunoreaction of GABA was remarkable in the superficial laminae of the dorsal horn. Many interneuronal somata in the substantia gelatinosa showed GABAergic immunoreactivity. The immunoreaction was seen in the entire GABAergic neuroplasm, but not in the nucleus and its envelope. Most GABAergic features appeared as dendrites making postsynaptic contact with CI- or CII-terminals; i.e., numerous C-terminals made presynaptic contact with GABAergic dendrites. GABA immunoreactivity was seen over round synaptic vesicles and mitochondrial membranes. A few CII-terminals made presynaptic contact with GABAergic interneuronal somata. Previous physiological and anatomical studies have suggested that not only the cutaneous nociceptive primary afferent C terminals but also mechanoreceptive primary afferent C-terminals make presynaptic contact with the GABAergic dendrites, boutons and soma. The presynaptic relation of these primary afferents with GABAergic neurons seems to provide morphological support for the essential feature of the gate control theory: primary afferent fibers may play a part in the modulation of nociceptive information via GABAergic neurons in the superficial dorsal horn. Small GABAergic terminals were found to make contact with blood capillaries suggesting the release of GABA into circulation. PMID- 1873077 TI - Histogenesis of the mucosa of the descending colon in mouse fetuses. AB - The present study clarify intraepithelial events occurring during the formation of intestinal crypts in the descending colon. In early stage, the mucosa is lined with a simple columnar epithelium consisting of undifferentiated cells which are mutually joined by the junctional complex surrounding the intestinal lumen. The epithelium becomes thickened and stratified, and secondary junctional complexes are formed in the abluminal part of the epithelium. An intracellular cavity opens to the focal tight junction of the secondary junctional complex to form an intraepithelial (intercellular) cavity surrounded by the tight junction. The intraepithelial cavity grows by the fusion of intracellular cavities and vesicles as well as by the division of surrounding cells. Intraepithelial cavities fuse with each other and with the main intestinal lumen. This, together with mesenchymal invasion, results in the formation of intestinal crypts lined with a simple columnar epithelium, where various cell types begin to differentiate. These processes seem essentially similar to those occurring in the developing small intestine except that villi, not crypts, are formed in the small intestine. It is suggested that the formation site and elongation of the tight junction provide for the location and fusion of intraepithelial cavities and eventually result in the formation of villi or crypts, alternatively. PMID- 1873078 TI - The quest for an AIDS vaccine: the state of the art and current challenges. AB - Despite intense efforts worldwide, using state-of-the-art methods and techniques and despite ever-increasing knowledge about the molecular and structural make-up of HIV, a practical vaccine against acquired immunodeficiency syndrome (AIDS) has yet to be developed. The increasing use of recombinant DNA techniques and synthetic peptide technology has allowed many groups to identify at the epitope level the regions of HIV proteins which act as targets for (and stimulate) the immune response. Epitopes which stimulate and bind neutralizing antibodies have been examined in detail and an ever-increasing number of antibody-dependent cellular cytotoxicity (ADCC) and cytotoxic T lymphocytes (CTL) epitopes are being defined, as are potentially harmful (immunosuppressive or enhancing) domains. It still is not clear which of the different immune responses (or combinations thereof) it will be necessary to stimulate in order to protect from infection. Infected humans develop neutralizing antibodies, ADCC-inducing antibodies and CTL responses against a variety of viral proteins but it is not known which of these can control or prevent infection in vivo. The extensive knowledge of HIV and the immune response it elicits is being used to design and produce a wide variety of putative vaccines, ranging from whole inactivated virus, through recombinant organisms/proteins, to synthetic peptides although each has its inherent advantages and disadvantages. The very nature of HIV makes vaccine development difficult at best. However, recent successes using whole inactivated virus or virus-infected cells in the macaque simian immunodeficiency virus (SIVmac) model system at least show that protection against lethal lentivirus infection can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873079 TI - Seroepidemiology of human T-cell lymphotropic virus type I/II in Benin (West Africa). AB - In 1988-1989, a national survey was conducted in Benin to determine the distribution of HTLV-I infection in a representative sample of adult individuals. This study comprised 2625 healthy subjects recruited in the six provinces of Benin and 1300 blood donors from Cotonou and from the other five provinces. Sera were screened for HTLV-I antibody by both immunofluorescence (IF) and enzyme immunoassay (EIA). Sera positive or doubtful by at least one technique were further analyzed by Western blot and radioimmunoprecipitation assay (RIPA) when indeterminate. Samples were considered as positive if they reacted with two gene products. No blood donor was positive. Over the 2625 subjects, 39 (1.5%) were positive. We observed a statistical difference between male and female (1%, 2%, p less than 0.05). A difference was also observed according to the areas studied: the HTLV-I antibody rate increased from coastal (0.3%) to northern (5.4%) provinces. HTLV-I seroprevalence increased significantly with age. This survey shows that HTLV-I infection exists in Benin but varies according to regions. PMID- 1873080 TI - Identification of a recombinant HTLV-II envelope protein for serological detection of HTLV-II carriers. AB - To understand the pathogenic potential and the true extent of human T-cell leukemia virus type II (HTLV-II) infection, it is important to develop a specific HTLV-II antigen-based serological test. Plasmid pIIB was constructed and induced in Escherichia coli to express a recombinant protein (RP) containing 140 amino acids (amino acid residues 96 to 235) from the middle region of the HTLV-II exterior envelope glycoprotein gp52. Serum samples from polymerase chain reaction confirmed HTLV-II-infected people, HTLV-I carriers, and adult T-cell leukemia (ATL) patients were tested for antibody reactivity to RP-IIB by Western blot assay. The results showed all 27 HTLV-II carriers, 10 of 20 HTLV-I carriers, and 4 of 17 (23.5%) ATL patients had antibody reactivities to RP-IIB. The difference in rates of seropositivity to RP-IIB between HTLV-II carriers (100%) and HTLV-I infected people (carriers plus ATL patients) (37.8%) is statistically significant (Fisher's exact test, p = 4.30E-08). PMID- 1873081 TI - Infection of human monocytes with HIV-1Ba-L. Effect on accessory cell function for T-cell proliferation in vitro. AB - Major laboratory manifestations of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) include altered levels of circulating CD4+ lymphocytes and decreased in vitro T-cell mitogenic responses. Since T-cell proliferation is regulated by monocytes (M phi), studies were undertaken to determine whether defective M phi function contributes to these poor mitogenic responses. M phi were isolated from peripheral blood mononuclear cells (PBMC) of normal donors by adherence to plastic. After 5 days in culture, the adherent cells were inoculated with the HIV-1 M phi-tropic strain, Ba-L. Under these conditions HIV infection in M phi can be detected 5-7 days after inoculation. Ten to fourteen days postinoculation, the adherent cells were harvested with lidocaine and cocultured with fresh autologous T cells and T-cell mitogens in a 3-day assay. We found decreased proliferative anti-CD3 responses to Leu4 and OKT3 and variable responses to concanavalin A (Con A) by T cells cultured with HIV-infected monocytes compared with T cells cultured with uninfected M phi. Supernatants from HIV-infected M phi cultures decreased proliferative responses of normal PBMC to anti-CD3 monoclonal antibodies. Heat activated supernatants had the same effect. Inhibitors of HIV binding did not restore proliferative responses of HIV-infected cultures to normal levels. These results indicate that HIV infection of M phi causes the release of soluble factor(s) that suppress anti-CD3-induced T-cell proliferative responses. PMID- 1873082 TI - Maturation of human immunodeficiency virus particles assembled from the gag precursor protein requires in situ processing by gag-pol protease. AB - The vaccinia virus expression system was used to determine the role of human immunodeficiency virus type 1 (HIV-1) protease in viral morphogenesis and maturation. The unprocessed p55 gag precursor polyprotein alone was assembled to form HIV-1 particles which budded from cells. The particles were spherical and immature, containing an electron-dense shell in the particle submembrane; there was no evidence of core formation. Expression of both gag and pol proteins from a recombinant containing the complete gag-pol coding sequences resulted in intracellular processing of gag-pol proteins and the production of mature particles with electron-dense cores characteristic of wild-type HIV virions. To ascertain the role of protein processing in particle maturation, the pol ORF in the gag-pol recombinant was truncated to limit expression of the pol gene to the protease domain. With this recombinant expressing p55 gag and protease, intracellular processing was observed. Some of the resultant particles were partially mature and contained processed gag protein subunits. In contrast, particle maturation was not observed when the HIV-1 protease and p55 gag were coexpressed from separate recombinants, despite evidence of intracellular gag processing. These findings suggest that HIV-1 protease must be an integral component of the full-length gag-pol precursor for optimal processing and virion maturation. PMID- 1873083 TI - [Molecule--hippocampus--memory. Part II: Hippocampus as a memory control apparatus]. PMID- 1873084 TI - [Transplantation of the sympathetic ganglion into the brain--induction of axonal outgrowth from the graft]. PMID- 1873085 TI - [Pathophysiological study of corona radiata infarcts by clinically available diagnostic methods]. AB - The authors evaluated 18 patients who presented with corona radiata infarction, one of the 'water-shed infarctions', on CT and/or MRI to determine its etiology and pathophysiology using cerebral angiography, single-photon emission computed tomography (SPECT), and tests of hemostatic function including hematocrit, platelet aggregation and adhesiveness. On angiography, 8 of these 18 patients had ulcerative lesions in the common carotid artery bifurcation with or without minimal stenosis and exhibited no or a minimal area of hypoperfusion localized to the corona radiata on SPECT. In these, microembolism from the lesions at the common carotid bifurcation seemed play an important role in the genesis of corona radiata infarction. In 7 of the remaining 10 patients, cerebral angiography showed occlusive lesions of the internal carotid artery around its origin in 3, more than 90% stenosis of the internal carotid artery in 1, severe stenosis of the M1 segment of the middle cerebral artery in 2, and M1 occlusion in 1. In 5 of these 7, SPECT demonstrated a larger area of hypoperfusion than the corona radiata in the involved hemisphere. In the remaining 2, SPECT demonstrated a hypoperfusion area localized to the corona radiata. In all 7, the hematocrit was elevated. A collateral blood supply was visualized in 5 of 7 on cerebral angiography. In these 7 patients, hemodynamic disturbance was considered to contribute to the pathogenesis of infarction in the corona radiata. In the final three patients, cerebral angiography showed significant occlusive lesions in the main trunk of the cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873086 TI - [Somatosensory evoked potentials by mechanical stimulation of tooth in humans]. AB - We examined topographical analysis of the PM-SEP (periodontal mechanoreceptor sensory evoked potential) inducing by mechanical stimulation of the tooth in eight subjects. Sensory evoked potential were recorded from various regions of the scalp by the mechanical stimulation of the normal tooth. Eleven electrodes were placed according to the International 10-20 system (T3, T4, C3, C4, T5, T6, F7, F8, Fz, Cz, Oz). The mechanical stimulation was applied to the right upper first incisor tooth. PM-SEPs were averaged 100 times following the mechanical stimulation of the tooth produced six waves of SEP at the ipsilateral temporal area (T4), but did not evoked any potential from the other regions. PM-SEP included I, II, III, IV, V and VI. The earliest latency (I wave) was approximately 11ms and latest latency (VI wave) was approximately 40 ms. These PM SEP observed by intensity with 3 times of the threshold. In addition, the all components were abolished after local anesthesia of the periodontal ligament. These data suggests that the six waves of the PM -SEP were evoked the ipsilateral temporal region following mechanical stimulation of the tooth, and these regions were projected by afferent impulse from the periodontal mechanoreceptor. PMID- 1873087 TI - [A case of divergence palsy associated with bilateral chronic subdural hematoma]. AB - A surgical case of bilateral chronic subdural hematoma presenting with divergence palsy is reported. A 75-year-old female was admitted to hospital for investigation of 2-week history of diplopia. The initial neurological examination demonstrated no abnormal findings except Hess chart suggesting bilateral concomitant strabismus or paresis of lateral rectus on both eyes. Because of the homonymous diplopia disappeared when the object of fixation in brought closer and the patient showed no impairment of gaze movements and following movements, the patient was diagnosed as divergence palsy and referred to the Neurosurgical Service. The physical examination revealed a 75-year-old, alert, fully oriented with diplopia at distant gaze. A computerized tomographic (CT) scan showed bilateral subdural hematoma. Emergency burrhole evacuation was performed and total amount bilateral hematoma was 220ml. Diplopia disappeared postoperatively. Hess chart examined two months after the operation shows no impairment of divergence function. This is the first reported case of divergence palsy associated with bilateral chronic subdural hematoma in CT era. PMID- 1873088 TI - [A case of pseudo-TSH.PRL-producing pituitary adenoma with secondary hypothyroidism]. AB - A 24-year-old housewife presented with weight gain of about 30 kg, constipation and pitting edema of extremity nine years after having a thyroidectomy. Hormonal examination revealed low levels of serum T3 and T4 and high levels of serum TSH and PRL. She also had enlarged pituitary gland (pituitary hyperplasia) with suprasellar extension on CT and MRI image. Thyroid replacement therapy and follow up by MRI were performed without resort to surgery, because she had no visual disturbance. Within about 1 month after thyroid replacement therapy, serum TSH and PRL were normalized. And also thyroid function was normalized by thyronine (T3). Following this results, pituitary hyperplasia regression was seen on MRI image. About 1 year after thyroid replacement therapy, pituitary hyperplasia regression was more seen on MRI image. Prolonged hypothyroidism can result in hypertrophy of the pituitary thyrotropin-secreting cells and prolactin secreting cells. So, it can increase pituitary weight (pituitary hyperplasia). Radiological examination, abnormal sellar x-ray films suggesting intrasellar tumor are common in patients with primary hypothyroidism. Suprasellar extension of pituitary mass (pituitary hyperplasia) due to hypothyroidism was reported by radiological examination (PEG, CT and MRI image), and regression of pituitary hyperplasia was revealed by radiological examination after thyroid replacement therapy. The first choice of this type of pituitary hyperplasia is thyroid replacement therapy unless the patient has a visual disturbance. However, if this replacement therapy is not effective for diminution of the tumor, surgical removal of the tumor should be considered. PMID- 1873089 TI - AIDS--a two-way risk. PMID- 1873090 TI - 'A 7-year review of maxillofacial trauma in a central London hospital'. PMID- 1873091 TI - AIDS testing for heath care workers. PMID- 1873092 TI - 'A denture of a lifetime'. PMID- 1873093 TI - 'A comparison of two splints in the treatment of TMJ pain dysfunction syndrome'. PMID- 1873094 TI - A comparative assessment of the strengths of porcelain veneers for incisor teeth dependent on their design characteristics. AB - An in vitro study, using dynamic stress analysis and two dimensional photo elasticity, carried out to relate the strength of porcelain veneers fabricated to three different designs, demonstrated that the 'window' type of preparation was the strongest compared with 'overlapped' and 'feathered' designs. It also confirmed that the strength of the veneer was not proportional to its thickness. It can be concluded that where strength is an important prerequisite, the most conservative type of veneer, namely the 'window' preparation, is the design of choice. PMID- 1873095 TI - The efficacy of comprehensive dental care for children under general anesthesia. AB - A review of 80 children treated under general anesthesia for comprehensive dental treatment between 1984 and 1987 inclusive was carried out to assess the effectiveness of this type of care. A minimum 2-year follow-up period was used. This approach allowed the dentition to be restored in one visit. Preventive care and 'behaviour shaping' could then begin at subsequent visits to the dental clinic. It was found that 80% of the children needing further treatment at a later date accepted local anaesthesia and treatment in the normal way. Full coverage stainless steel crowns were significantly more successful (3% failure rate) than amalgam or composite restorations (29% failure rate). Vital pulpotomies also showed only a 2% failure rate. PMID- 1873096 TI - Oral presentation of the Laugier-Hunziker syndrome. AB - Laugier-Hunziker syndrome is an extremely rare disorder but is of some interest to dental practitioners. The importance of the condition relates to it being included in the differential diagnosis of pigmentary disorders of the oral mucosa with associated nail involvement. Two cases of the syndrome are described. PMID- 1873097 TI - Oro-antral fistula: an unusual complication of HIV-associated periodontal disease. AB - Oral lesions have been reported frequently in patients seropositive for human immunodeficiency virus. A case is reported of HIV-associated periodontitis complicated by necrotising stomatitis and the development of an oro-antral fistula; the role of extractions in the management of this condition is highlighted. PMID- 1873098 TI - Why free sugars consumption should be below 15 kg per person per year in industrialised countries: the dental evidence. AB - The World Health Organization and COMA have recommended that free or non-milk extrinsic sugars intake should be below 10% of total energy intake and the COMA report on dietary sugars and human disease has strongly implicated sugars as the main causative factor in dental caries. The scientific basis for the conclusions of these important policy documents has been challenged by the sugar and confectionery industries. Dental evidence is presented to substantiate the WHO recommendation. The dose-response curve for sugar and caries is approximately sigmoid (S-shaped). At levels of sugar consumption below 10 kg/person/year the incidence of caries is acceptably low. Beyond 15 kg the incidence increases more rapidly. Fluoride increases the resistance of teeth to sugar--it moves the dose response curve to the right. Thus, when fluoride is widely available, the acceptable level of non-milk extrinsic sugars increases to about 15 kg/person/year. PMID- 1873099 TI - In harm's way. PMID- 1873100 TI - Classification of nursing interventions for care of the integument. AB - The Classification of Nursing Interventions research team at The University of Iowa, College of Nursing is building a taxonomy of nursing interventions that will include all of the direct care treatment activities that nurses perform on behalf of patients. This report describes the study in which 12 nursing interventions and their associated activities for care of the integument were extracted from a large database and validated through a two-round Delphi survey. Using an adaptation of Fehring's model for determining diagnostic content validity of nursing diagnoses, a definition, critical activities, and supporting activities were developed for each of the following interventions: Bathing, Bedrest Care, Hair Care, Nail Care, Oral Health Maintenance, Oral Health Promotion, Oral Health Restoration, Positioning, Pressure Management, Skin Care- Topical Treatments, Skin Surveillance, and Wound Care. Further research is needed to validate supporting activities and to continue classifying interventions and activities that nurses use in treating impaired skin integrity (potential and actual) and altered oral mucous membrane integrity (potential and actual). PMID- 1873101 TI - Multinational validation of anxiety, hopelessness, and ineffective airway clearance. AB - The effective use of nursing diagnosis internationally depends in part on incorporating language and cultural difference into the common language of nursing. International validation studies can provide a basis for this effort. This study tested three diagnoses--anxiety, hopelessness, and ineffective airway clearance--through multinational validation. The Diagnostic Content Validity (DCV) model was used to collect data from critical care nurses in six countries. Defining characteristics rated as critical (greater than .80) by the total sample were dyspnea for ineffective airway clearance and panic and nervousness for anxiety. No critical defining characteristics for hopelessness were identified. DCV ratios for all defining characteristics are compared by country. PMID- 1873102 TI - Dyspnea: a case for nursing diagnosis status. AB - Dyspnea, the unpleasant subjective sensation of difficult breathing, is one of the most common symptoms experienced by patients with pulmonary and cardiac disorders. This article reviews the research concerning dyspnea and proposes it for consideration as a nursing diagnosis. The etiologies are categorized according to the neurosensory, neurochemical, cognitive, and affective mechanisms. The defining characteristics include the subjective words describing dyspnea, such as shortness of breath, suffocation, and tightness. The most supported objective sign of dyspnea in the literature is an increased use of accessory muscles of respiration. Nursing interventions for dyspnea relief are geared toward reducing the afferent activity from receptors in the respiratory muscles and dealing with the affective component of dyspnea. These interventions include pacing activities, breathing techniques, and inducing the relaxation response. Because most research for interventions to reduce dyspnea have focused on patients with obstructive lung disorders who have chronic dyspnea, recommendations for further research include using acutely ill patients and those with a variety of medical conditions. PMID- 1873103 TI - Clinical nurses' characterizations of patient coping problems. AB - The author reports the findings from a qualitative study of diagnostic data obtained and interpreted by hospital nurses on the coping of adult patients and their families. Clinical data taken from taped interviews were transcribed and analyzed using grounded theory and analytic induction techniques. The data were then compared with diagnoses accepted for testing by NANDA. The phenomena described by the research did not match the NANDA constructs for individual and family coping problems. Nurses' assessments of coping response, however, fit within transactional theory. The use of the term "ineffective" to qualify coping was generally avoided. Ineffective coping, suggesting an outcome or product of coping, was not often considered applicable to the coping responses nurses found appropriate at specific times in specific situations. PMID- 1873104 TI - Name that nursing diagnosis: a gaming-simulation. PMID- 1873105 TI - [Prognostic factors in craniocerebral trauma without primary surgically correctable space occupying lesion]. AB - By means of a retrospective study involving 154 patients with diffuse brain injury, we could show, that simple factors, like coexisting injuries, pupil abnormalities and the Glasgow coma scale, allow us to assess the prognosis of patients outcome a short time after trauma. This prognosis is further modified by cerebral perfusion pressure and secondary pupil abnormalities. The prognostic value of an EEG and a SEP is the same for both methods and was found to be correct in about 2/3 of all cases. PMID- 1873106 TI - [Surgical treatment of Achilles tendon rupture]. AB - Ruptures of the Achilles tendon are rare, but their incidence seems to become higher due to changes of life style and to increasing sports activities. Concerning the optimal therapy--conservative or surgical--there still exist diverging opinions. In our clinic, we have always preferred surgical therapy. We present a survey of the results of surgical treatment in 139 patients. Based on our own experience and on a literature review we recommend surgical therapy for rupture of the Achilles tendon, mainly in view of the high incidence of reruptures after conservative treatment and the existing functional results. PMID- 1873107 TI - [Soft tissue pain and psychiatric evaluation]. AB - Attention is drawn to the special position of the psychiatric assessor. In his evaluation, the assessor takes into consideration psychic and somatic findings and also social factors. Precisely in connection with the assessment of soft tissue pain there is a growing recognition that the Ancient Greek dualism of "psyche and soma" is already obsolete. Psychic and somatic factors are mutually dependent, and psychosomatic illness has a multifactorial origin involving predisposition, the development of the personality in early childhood and later, and finally the development of environmental influences in the individual sphere and in the social sphere in general. A subject of special discussion are personality factors which are correlated with a developmental impairment of aggressive motivation. The inhibition of aggression seems to play a decisive role in determining the symptoms. The loss of constructive aggressivity is presented as a trigger for soft-tissue pain. PMID- 1873108 TI - [Medical evaluation of work capacity]. PMID- 1873109 TI - [Management of war injuries from the anesthesiologic point of view: a report of experiences from the IKRK hospital in Kabul, September 1990]. AB - We report the medical experience during a 3 week stay in the ICRC hospital of Kabul as anaesthesist. 170 war wounded patients had been treated following clear and simple rools of war surgery. The anaesthetic management and the important role of Ketamin is explained. PMID- 1873110 TI - [The "severity" of "whiplash injury of the cervical spine"]. AB - The severity of the so called "whiplash injury of the neck" ("soft tissue neck injury") and the condition thereafter depends on the chosen angle of view: impact dynamics, biomechanics, pathological-anatomical considerations, clinical and apparative findings, medicolegal aspects and subjective assessment. The impact itself may not serve as a diagnosis, which latter has to be founded on the results of the medical examination. These findings seem to be appropriate for the resolution of questions in the course of litigation. At present, a universal severity may not be defined. PMID- 1873111 TI - NMR, CD and MCD studies of vanadate-nucleoside complexes. AB - Complex formation between tetraoxovanadate(V) and each of the nucleosides adenosine, guanosine, cytidine and uridine has been studied in a constant salt medium at pH 7. 13C- and 51V NMR studies show that only complexes with the formula V2L2 (V = vanadate, L = nucleoside) are formed, and their formation constants have been determined. They have 51V NMR resonances around -523 ppm relative to VOCl3 and they exhibit no CD in the spectral region of the charge transfer transitions. MCD spectra were also measured, and all experiments are in accord with a molecular structure composed by two edge-sharing VO6 octahedra forming an O4V(mu-O)2VO4 skeleton with each of the nucleoside ligands bridging the two vanadium centres through the ribose 2',3'-oxygens, which are the oxygens outside the V2O6 plane. Admixture of imidazole-HCl buffer at pH 7 gives rise to additional complexes of 1:1 stoichiometry. They have been characterized by 51V NMR and CD, and their formation constants are reported. Vanadate(V) and the deoxynucleosides deoxyadenosine, deoxyguanosine, deoxycytidine and thymidine form very weak complexes which cannot be detected by 51V NMR or CD under conditions for which vanadate and the nucleosides form complexes. PMID- 1873112 TI - Weaning from long-term mechanical ventilation. PMID- 1873113 TI - Respiratory pharmacology and the weaning patient: implications for critical care nursing. AB - The process of weaning patients from mechanical ventilation may be facilitated by the appropriate selection and use of bronchodilators, mucolytics, steroids, and sedatives. This article discusses implications for the critical care nurse, focusing on the indications, applications, and evaluations of the drugs most commonly administered to patients prior to or during weaning from mechanical ventilation. PMID- 1873114 TI - Weaning from mechanical ventilation: a method for assessment and planning. AB - Weaning patients from mechanical ventilator assistance is difficult and often requires the input of experts. Though researchers have identified numerous factors that impede weaning and continue to develop criteria to determine ability to wean, no single factor or set of criteria have yet emerged to guide clinicians. In an effort to design a tool that assists critical care nurses in forwarding the wean process, the authors developed a comprehensive, integrated, computerized ventilator weaning program that stimulates the thinking and care planning strategies of experts. The Burns Wean Assessment Program also teaches complex concepts and tracks the progress of the weaning patient. PMID- 1873115 TI - Auto-PEEP: an impediment to weaning in the chronically ventilated patient. AB - Auto-positive end expiratory pressure (auto-PEEP) is a physiologic event that is a recently recognized phenomenon common to mechanically ventilated patients. Auto PEEP occurs when forces exist that limit expiration and the subsequent elimination of positive pressure from the lungs. If positive pressure is retained, a potential reduction in cardiac output and increase in complications from barotrauma arise. Because of possible physiologic problems associated with it, auto-PEEP can potentially interfere with weaning from mechanical ventilation. Nursing measures that can reduce the effect of auto-PEEP during weaning are centered on improving the inspiratory/expiratory flow patterns. These efforts include manipulating mechanical ventilator settings and reducing causes of increased respiratory rates (e.g., pain and anxiety). Since auto-PEEP was only recently identified as a potential impediment to weaning from mechanical ventilation, the nurse must be aware of the need to assess for the presence of auto-PEEP in these patients. PMID- 1873116 TI - Standardizing the weaning process. AB - The goal among critical care staff of discontinuing mechanical support in a prudent and expeditious manner emerges immediately after intubation. This goal, known as the weaning process, contains the three phases of optimizing the patient's condition, assessing and evaluating the patient's progress, and diagnostic testing. As a diagnostic test, the wean trial needs to be standardized for efficiency and safety. To maximize safe and efficient delivery of the trial, the primary nurse and respiratory therapist should be the responsible professional monitors. The standardized trial enhances staff confidence for safe extubation. A successful standardized weaning protocol eases the transition from mechanical ventilation to spontaneous breathing for the patient and improves the professional performance and confidence of critical care staff. PMID- 1873117 TI - Respiratory muscle conditioning and the work of breathing: a critical balance in the weaning patient. AB - Normal ventilatory function depends on a balance between ventilatory demand and ventilatory capacity. The respiratory muscles play a critical role in achieving this balance. For patients experiencing ventilatory dysfunction, interventions that improve respiratory muscle function and therefore increase ventilatory capacity may be one way of restoring the balance and promoting ventilatory function. Respiratory muscle conditioning, or training the muscles to improve their strength and endurance, may be a useful clinical intervention in the weaning patient. Results of research show that muscle training may increase the ability of some patients to resume spontaneous ventilation. Continued research is needed to identify the appropriate training protocols for patients experiencing an acute imbalance between ventilatory demand and capacity. PMID- 1873118 TI - Chronic hypoventilation syndrome: treatment with non-invasive mechanical ventilation. AB - Chronic hypoventilation syndrome can be caused by many disease states, although it is more commonly seen in neuromuscular disorders. Assessment of hypoventilation includes measurement of carbon dioxide level, respiratory muscle strength, pulmonary function testing, and any other system involved, such as cardiac dysfunction or sleep abnormalities. Often, chronic hypoventilation is initially diagnosed during an episode of acute respiratory failure. The use of noninvasive ventilation with positive pressure, negative pressure, or gravitational devices can be an effective treatment option for some patients, thus obviating the need for a tracheostomy. Noninvasive ventilatory equipment such as the nasal or oral masks, mouthpieces, bi-level positive airway pressure, chest cuirasses, ponchos, or the iron lung, and the rocking bed or pneumobelt can each ventilate a certain type of patient adequately. Each has specific indications, advantages, and disadvantages and must be individualized to the patient's needs. PMID- 1873119 TI - Psychosocial concerns of the ventilator-dependent child in the pediatric intensive care unit. AB - An increasing number of infants and children suffer from respiratory and neuromuscular diseases that render them ventilator-dependent. These patients spend months in pediatric intensive care units (PICUs) until they are either extubated or are stable enough to tolerate home ventilation. The critical nature of the PICU and its emphasis on meeting short-term goals is not readily compatible with the long-term and dynamic needs of developing children. In order to prevent the delays in growth and development that often occur during prolonged hospitalizations, this article addresses the impediments to normal growth and development in the PICU and offers specific suggestions on how the environment and nursing care can be changed to support the development of ventilator dependent children and their families. PMID- 1873120 TI - Chest physiotherapy in neonates: a review. AB - Chest physiotherapy (CPT) is performed on neonates with actual or potential pulmonary problems. The focus of this review is on research related to the effectiveness of or the physiologic alterations related to CPT. Findings from this review indicate that CPT in neonates: 1) did not significantly improve oxygenation or secretion removal in the first 24 hours of life in premature infants with respiratory distress syndrome, 2) increased oxygen consumption, and 3) prevented post-extubation atelectasis. Nursing considerations when performing this procedure, contra-indications, and documented side effects are included in this review. PMID- 1873121 TI - Dyspnea in the weaning patient: assessment and intervention. AB - Dyspnea, the subjective sensation of uncomfortable breathing, is frequently experienced by patients during weaning from mechanical ventilation. As the clinical manifestation of increased work of breathing, dyspnea can be a valuable predictor and indicator of changes in patient respiratory status during the weaning process. The importance of measuring dyspnea is emphasized and the numerical rating and visual analog scales as direct measures of dyspnea are described. The most reliable physiologic variables that can be used to indirectly estimate dyspnea are discussed. Strategies such as positioning, coaching, "bagging," inspiratory muscle training, pressure support ventilation, oxygen, and relaxation/biofeedback techniques that can be used by the critical care nurse to decrease dyspnea are suggested. PMID- 1873122 TI - Cardiac assist devices. PMID- 1873123 TI - Mechanical support beyond the intra-aortic balloon pump. AB - The ventricular assist device (VAD) is one of the latest tools available to help the clinician contend with severe heart failure. This article presents a historical overview of the development of the VAD and discusses the incidence and etiology of heart failure. The investigational device research process, nursing involvement, and future trends are discussed. PMID- 1873124 TI - Current perspectives on the use of circulatory assist devices. AB - An overview of currently available circulatory assist devices (CADs) is presented with discussion of each system's optimal use and limitations. Successful application of CAD technology for bridge to transplant or pending recovery of the natural heart requires understanding issues involving team readiness, patient selection, device limitations, patient management, and complications. Currently, many of these devices are in clinical trials with the Food and Drug Administration (FDA). The FDA and the National Institutes of Health play major roles in the ongoing development of this technology. In the near future the learning curve continues as totally implantable systems are used. The ultimate goal is to maintain patients with heart failure on implantable devices with a good quality of life at a reasonable cost. PMID- 1873125 TI - Nursing considerations for patients requiring cardiopulmonary support. AB - The number of patients receiving cardiopulmonary support (CPS) is increasing, requiring critical care nurses to be better prepared to care for these complex patients. Background information on CPS along with considerations for nursing management are presented. A case study of a patient requiring CPS and a suggested nursing care plan are included to assist in providing quality nursing care. PMID- 1873126 TI - Centrifugal ventricular assist devices. AB - A centrifugal ventricular assist device (VAD) uses centrifugal force to propel blood through nonocclusive pumpheads. Blood is diverted from either the right atrium or left atrium to a disposable pumphead. Then kinetic energy is added to blood contained within the VAD by rotating it at high speed. Centrifugal force generates energy which causes the blood to rise from the pumphead's base, thus forcing a return flow direction. Centrifugal VAD design has been used to sustain myocardial function when patients could not be weaned from cardiopulmonary bypass and as a bridge to transplantation. Interaction between centrifugal VAD and human hosts are complicated and multisystemic. Therefore a multidisciplinary VAD support team is most efficacious. A case study, nursing diagnoses, and care plan provide a comprehensive overview of nursing management for this patient population. PMID- 1873127 TI - The Thoratec ventricular assist device: nursing guidelines. AB - The Thoratec ventricular assist device (VAD) offers a final hope for survival in patients with severe cardiogenic shock unresponsive to conventional therapy. In select patients, these pneumatically activated prosthetic ventricles maintain organ perfusion pending recovery of the native heart or cardiac transplant. A detailed review of Thoratec VAD operation, its impact on the circulatory pathway and hemodynamic monitoring, and troubleshooting guidelines specific to these patients are presented. A nursing diagnosis framework assists with the identification and management of problems such as impaired cardiac output and gas exchange, as well as altered mobility, nutrition, and coping. Current information regarding the etiology and management of complications such as bleeding, infection, and end-organ failure are reviewed. A case study presentation offers guidelines for weaning patients from the VAD and includes a comprehensive nursing care plan for these challenging patients. PMID- 1873128 TI - Thermo cardiosystems left ventricular assist device as a bridge to cardiac transplant. AB - In 1986, clinical trials were initiated with a left ventricular assist device capable of supporting individuals in end-stage heart disease for extended periods of time (longer than 14 days). While supported by this device, patients were hemodynamically stabilized for future transplant and were afforded an opportunity to improve their overall health status. At initiation of support these patients were in New York Heart Association class IV, and within approximately 2 weeks, improved to class I. Their nutritional status improved, they were able to exercise regularly, and they became the "healthiest" candidates for cardiac transplant. Nursing care of a patient requiring the HeartMate provides the critical care nurse with new challenges. PMID- 1873129 TI - The ABIOMED BVS 5000 system. AB - The ABIOMED BVS 5000 system is an investigational pulsatile biventricular assist device. Positioned externally, pneumatically driven two-chambered blood pumps can support one or both sides of the heart. A single console automatically adjusts beat rate and systolic/diastolic ratio based on compressed air flow into and out of the external system. Transthoracic cannulae connect the external system with the patient. Two patient groups are currently approved for BVS investigational use: post-cardiotomy ventricular dysfunction and post-acute myocardial infarction with cardiogenic shock. Established research protocols are followed with regard to data collection. Potential adverse effects fall into three categories: patient related, device related, and cause unknown. Weaning is initiated during cardiac recovery, and if it is successful, the pump is removed. Nursing care is based on standards of care for cardiac surgery coupled with the ABIOMED BVS 5000 nursing protocol. PMID- 1873130 TI - The Hemopump temporary cardiac assist system. AB - The Hemopump temporary cardiac assist system is currently in clinical trials at several centers across the United States and abroad. Patients with postcardiotomy low cardiac output or patients with cardiogenic shock secondary to acute myocardial infarction may greatly benefit from this device. Theory of pump operation, patient selection, and nursing management is discussed. Presentation of a case study demonstrating the effect of Hemopump support will be provided. A detailed nursing care plan as well as application of research findings to clinical practice will be outlined. As cardiovascular technology progresses, the critical care nurse must continue to be involved in all aspects of patient care. The Hemopump may prove to be a highly beneficial mode of ventricular assistance for patients with inadequate cardiac function. PMID- 1873131 TI - Novacor left ventricular assist system. AB - Clinical investigation of the Novacor ventricular assist system has been ongoing since 1984. Major successes have been achieved using the device as a bridge to heart transplant. This system uses an electrically driven, pulsatile pump implanted in the left upper abdominal quadrant. The system has demonstrated the ability to provide long-term patient support, a feature that allows patients to become mobile and active once recovered from their initial heart failure. By the time of transplant, nutrition is restored, activity tolerance is improved, and most patients require no inotropic support. The system allows patients to recover from cardiogenic shock by providing total systemic circulatory support. PMID- 1873132 TI - The total artificial heart. AB - In the early 1800s, an awareness of potential ventricular failure stimulated interest in artificial heart replacement. In 1937 the first total artificial heart (TAH) was implanted into the chest of a dog by Russian physicians. The primary driving force for mechanical cardiac assistance developed from the necessity for circulatory assistance in order to perform corrective cardiac surgery. In 1953 the first successful closure of an atrial septal defect using extracorporeal circulation was performed. During the following decade the concept of using mechanical devices to assist the failing heart was aggressively pursued. This culminated in the first implant of a TAH in a human in 1969 as a bridge to transplant. Clinical implant of the TAH as a permanent device was performed in 1982 by researchers at the University of Utah. This patient lived for 112 days. Three successive permanent implants were performed in Louisville, Kentucky, with one patient surviving for 620 days. All of these permanent TAH patients suffered from device-related complications including bleeding, infection, and thromboembolic events. It became apparent that the present configuration of the TAH with its external drive lines and large air console was not ideal for long term support. In 1985 the first implant of the Symbion J-7-100 TAH (Jarvik-7) as a bridge to transplant was performed. This patient was supported by the device for 9 days and was successfully transplanted and discharged home. Since 1985 more than 170 patients have been bridged using the Symbion J-7 TAH with more than 70% of these patients being successfully transplanted. The incidence of thromboembolic events has dramatically reduced with better understanding of anticoagulation requirements. Infection continues to be the greatest potential complication with these patients. In spite of this, the pneumatic TAH has proved to be an adequate bridge to transplant device. PMID- 1873133 TI - Cardiac assist devices as a bridge to cardiac transplant. AB - The number of heart transplants being performed in the United States over the last decade has increased significantly. The supply of human donor hearts has not kept up with the demand. This situation has led to the development of means to support patient's cardiac function until a human donor heart can be obtained. Methods to support the patient include use of ventricular assist devices and the total artificial heart. Integration of caring and technology in patients receiving cardiac assist devices (CADs) provides a challenge for critical care nurses. Nursing care of the patient with a CAD involves identification and prevention of complications, familiarization with new technology, and development of a caring environment. PMID- 1873134 TI - HIV/AIDS education in a prenatal clinic: an assessment. AB - An HIV/AIDS education and counseling program was integrated into the routine medical care of women attending the prenatal clinic of a major urban, inner-city, teaching hospital that serves mostly indigent minority women in an area hard hit by the HIV/AIDS epidemic. Pre- and post-intervention questionnaires were administered to a consecutive historical Control Group (n = 98) who did not receive the HIV/AIDS information and an Intervention Group (n = 515) who received all information. The data support our hypothesis that an HIV/AIDS education program would increase the level of general knowledge, but fail to support our hypothesis of a positive effect on attitudes around HIV-antibody testing and an increase in desire for voluntary testing. Our hypothesis that women reporting more risk behaviors would be more likely to agree to HIV-antibody testing was only partially supported. PMID- 1873135 TI - Incorporating HIV education and counseling into routine prenatal care: a program model. AB - This article reports how a prenatal clinic in a major urban teaching hospital has developed and integrated an HIV education and counseling program into routine prenatal care. The patient population served are predominantly minority women living in an inner-city community that has been disproportionately affected by the AIDS epidemic. Implementation of the patient program has required training and support for all professional staff. Staff training served as a foundation for this comprehensive patient program, which has reached all prenatal patients regardless of risk behavior. The program has succeeded in involving a large population of women in an educational program, has identified HIV-1 seropositive pregnant women through voluntary testing, and has provided them with the necessary medical and social work services. Principles of program development are identified for use in other settings. PMID- 1873136 TI - Medical student attitudes toward the treatment of HIV-infected patients. AB - The intention to treat HIV-infected persons and correlates of those intentions were examined in a cross-sectional sample of 1st- and 2nd-year medical students (n = 201). An anonymous questionnaire measured knowledge of HIV transmission, intention to provide medical care to HIV-infected persons, comfort in performing a physical examination on patients from subgroups with high HIV prevalence, level of homophobia, professional altruism, and personal perceived risk of HIV infection. Intention to provide medical care was considered as the dependent variable. All variables except perceived personal risk were found to be significantly related to the intention to provide medical care although knowledge showed the weakest relationship (Odds Ratio = 2.14). The presence of professional altruism and the presence of homophobia were associated with a significant increase in the effect of knowledge on increasing the intention to treat. Results of this report support other studies that showed that factors other than knowledge play a role in clinical decision making regarding patients with AIDS. PMID- 1873137 TI - The impact of religion and cultural values on AIDS education programs in Malaysia and the Philippines. AB - This paper examines the impact of cultural values and government policies on the content of AIDS educational literature prepared by public health agencies in Malaysia and the Philippines. The literature from these countries, which has been distributed to the public and is intended to inform them of the danger of AIDS, how the HIV is and is not transmitted, and how to avoid infection, is analyzed and evaluated for effectiveness and congruence with the dominant religious tenets and cultural practices in each country, and attitudes to sexual behavior. The paper also describes the response of these countries to the AIDS pandemic, and concludes with suggestions about how this form of AIDS education can be improved. PMID- 1873138 TI - AIDS prevention and education: reframing the message. Citizens Commission on AIDS for New York City and Northern New Jersey. PMID- 1873139 TI - Social/sexual norms and AIDS in the South. Ethics and the politics of aids: lessons for small cities and rural areas throughout the U.S. AB - No one denies that the face of AIDS (the "AIDS profile") is changing, and it is clear that we are entering a new phase in our understanding of this disease. As the AIDS profile changes, however, we are seeing a change in attitudes about prevention. In this stage of the epidemic there seems to be a move toward adopting more coercive strategies for breaking the chain of transmission. One concern, obviously, is that newly HIV-infected persons will find that they have little capacity to demand recognition of their rights to consent, to be treated, to confidentiality, to move about freely in society, to work, and so on. Unfortunately, this bodes ill for newly infected persons in previously low incidence areas. Two very recent studies suggest that rates of high-risk sexual behavior among homosexual/bisexual men in smaller cities and rural areas in the South are much higher than rates now reported for gay men in large city epicenters. This paper attempts to examine the implications of differences in social and sexual behavior norms in the South for the spread of AIDS/HIV and to suggest morally appropriate primary prevention strategies for working within them. PMID- 1873140 TI - AIDS knowledge and risk behaviors among culturally diverse women. AB - This article reports results from a survey of women at risk for HIV infection. The sample (n = 620) included black (50.6%), white (28.7%), Hispanic (13.4%), and Haitian (5.0%) adult women from south Florida. Data concerning their AIDS knowledge, prevalence of risk behaviors, and perceived vulnerability are presented. Results indicate differences in certain knowledge areas and risk behaviors by race/ethnicity and a consistent incidence of unprotected sex with their main partners across all racial/ethnic groups. PMID- 1873141 TI - Development of AIDS education and prevention materials for women by health department staff and community focus groups. AB - The New York City Department of Health (NYCDOH) has developed a comprehensive, empowering, and educational booklet for women in response to (1) the rapid increase in AIDS among women; (2) the lack of woman-specific, current, language appropriate literature; and (3) the need to address the multitude of direct and indirect effects of the HIV/AIDS epidemic on women. Drafts of the booklet were developed during a 12-week series of consensus-driven meetings attended by a core group of women from various professional and personal backgrounds. Following NYCDOH approval, community focus groups reviewed the booklet to ensure that it met the needs of targeted women, community HIV/AIDS educators and other health and social service providers. This paper describes the issues encountered when designing materials for women of diverse cultures and roles (e.g., pregnant women, IV drug users, lesbians), as well as the dynamics of the development process and its benefits and difficulties. Criteria and guidelines for this development process are outlined. PMID- 1873142 TI - [Current views and controversies about reconstruction after esophagectomy]. AB - The Authors examine the reconstructive procedures following total or partial esophagectomy, reporting advantages and disadvantages related to stomach, colon or jejunum transposition. The stomach is certainly the organ most widely employed for its adaptability and excellent vascularization; furthermore, only one anastomosis is needed. After a short note on pathophysiology of the most common complications, the Authors point out the advantages of using stapling devices, with special attention to the low incidence of anastomotic dehiscence. PMID- 1873143 TI - [Reconstructive techniques in malignant tumors of the sternum]. AB - The Authors analyze the main surgical techniques for the treatment of malignant sternal neoplasms. Their experience in two cases of sternal chondrosarcoma is reported. Techniques of reconstruction of the chest wall as well as long-term results are described. PMID- 1873144 TI - [Surgical treatment of alkaline and mixed reflux after surgical interventions on the stomach]. AB - The Authors report their experience in the surgical management of 13 cases of alkaline and/or mixed type gastroesophageal reflux (GER) secondary to gastric surgery. In 5 cases the gastroesophageal "diversion" "technique" proposed by the Authors, was used. Results obtained with this procedure (clinically and instrumentally evaluated) are presented. PMID- 1873145 TI - [Arthroscopy in acute dislocation of the patella: a new surgical technique]. AB - The adequate treatment for acute patellar dislocation is still controversial. The Authors describe a new surgical arthroscopic technique to repair medial retinaculum rupture, which is the most common lesion in the acute patellar dislocation. Compared to arthrotomy arthroscopic treatment eliminates post operative pain and shows the same advantages in reducing recurrences. PMID- 1873146 TI - [Proctocolectomy and mechanical ileo-anal anastomosis without mucosectomy]. AB - The present study compared the outcome in a small series of patients (7 cases) who underwent total proctocolectomy without mucosal proctectomy and stapled ileal pouch-anal anastomosis, constructed at the apex of the anal transitional zone, with our previous experience (17 cases) in which the ileal pouch was anastomosed at the dentate line after mucosectomy. Though not statistically significant, our limited experience showed excellent clinical results with better continence and discriminating ability between gas and faeces in the former group. The resting anal pressure profile showed no chances in the postoperative period. The operation time was significantly reduced compared with our previous approach which was a time-consuming procedure. Furthermore, a reduced risk of complications (pelvic sepsis, haemorrhage) was observed. PMID- 1873147 TI - [Anastomosis or closure of the pancreatic stump after duodenopancreatectomy?]. AB - From 1986 to June 1990, 10 pancreaticoduodenectomies were performed in our Department (VIII Patologia Chirurgica, Universita "La Sapienza", Roma). The reconstructive sequence was based on the pancreaticojejunal anastomosis (2 end-to end pancreaticojejunostomies after invagination, 3 end-to-side Wirsung jejunostomies) in 5 patients. The pancreatic stump was sutured using a 50mm linear stapler in the remaining 5 patients. There was a high incidence (75%) of fistulization after direct suture of the pancreatic stump, although related mortality was null. Among patients treated with pancreaticojejunal anastomosis, a fistula on the end-to-end pancreaticojejunostomy with exitus of the patient, was registered in 1 case. On principle, we believe a end-to-side Wirsung jejunostomy should be performed after pancreaticoduodenectomy. When a safe anastomosis of the pancreatic stump cannot be performed (because of the soft parenchyma, easily lacerable) the technique of the direct suture with stapler is advisable. PMID- 1873148 TI - [Knight-Griffen ileo-proctostomy after total colectomy]. AB - The double stapled colo-rectal anastomosis according to Knight e Griffen is currently used following an anterior resection of the rectum. The technical feasibility and the reduced risk of contamination represent the major advantages of the procedure. Accordingly, the Authors have adopted this technique to perform an ileo-rectal anastomosis following total colectomy. Furthermore, the use of a circular stapler with a small diameter allows to create a pseudo-valvular mechanism between the ileum and the rectum. Preliminary results obtained in 7 patients are presented. PMID- 1873149 TI - [Problems in emergency visceral reconstruction in colorectal pathology]. AB - A diagnostic-therapeutic protocol for colorectal haemorrhage is suggested. The Authors underline the need to remove inflammatory foci when a perforation of the colon occurs; furthermore, in the acute obstruction due to colorectal carcinoma a resection followed, when possible, by an immediate anastomosis is recommended. PMID- 1873150 TI - [Reconstructive microsurgery]. AB - Progress in microsurgery has been accomplished by the technical improvements of the operative microscope and other delicate surgical instruments. Therefore, even small arteries as well as female tuba and male deferens, either presenting mechanical obstruction or a section, can be reconstructed. The same procedure may be applied in case of nerve injuries. Since Microsurgery was born, it has been employed in different medical fields offering lately good chances in sterility. Furthermore, microsurgical techniques offer a great support to Plastic Surgery. In fact, it is possible to repair wide tissue damages of the skin, muscles or bones using free flaps. The percentage of success of this Surgery increased the overall percentage obtained in General Surgery. Therefore a close multidisciplinary relation between the different Medical fields is absolutely required for a correct application of microsurgical techniques. PMID- 1873151 TI - [Current aspects and controversies in reconstructive surgery after esophagectomy: personal experience]. AB - The authors report their series of 184 esophagectomies performed both for benign (44) and malignant (140) diseases. On the basis of their experience and supported by Literature data, it is believed restoration of digestive continuity offers two main points of discussion: choice of the intestinal tract for the interposition and type of anastomosis to perform. The nature of the lesion and its level seems to play the most important role in the choice. PMID- 1873152 TI - [Pancreatoduodenectomy with preservation of the stomach and pylorus: technical and functional aspects]. AB - Pancreatoduodenectomy is the most used resective operation in the treatment of cephalopancreatic pathology; nevertheless it is a severely demolitive operation, especially if performed according to the traditional technique. It can induce early as well as late complications in a high percentage of cases. A number of technical improvements have been proposed so far in order to reduce or avoid such complications; duodenopancreatectomy with gastric and pyloric preservation (PPDP) is the most representative one. The Authors analyze technical and functional features of PPDP in 22 patients operated on; results are compared with the traditional technique. In conclusion, among all the techniques proposed, PPDP assures the best improvement in the quality of life of these patients. PMID- 1873153 TI - [Closure of the residual pancreatic stump after pancreatoduodenectomy using a mechanical stapler]. AB - An important technical problem during pancreatoduodenectomy is the treatment of the pancreatic stump. The Authors describe their recent experience in five cases of pancreatoduodenectomy, in which the pancreatic stump, including the Wirsung, was closed using a linear stapler. An outflow of clear pancreatic juice through the drainage tubes was registered postoperatively, in all patients. The flow of the fistula was very limited in 4 cases and the healing occurred within two weeks; only in one case the drainage was initially more than 200 ml/die, but a spontaneous healing occurred after 28 days. PMID- 1873154 TI - [A new reconstructive model after total proctectomy]. AB - The Authors describe a new reconstructive model after total proctectomy: the S-E colo-anal anastomosis (S-E CAA). The technical requisites of this variant are discussed and compared with more traditional reconstruction models. At a first evaluation of the results, the S-E CAA seems to be able to sensibly ameliorate the course and the outcome of the anastomosis and to hasten the recovery of the normal sphincteric function. PMID- 1873155 TI - [Partial splenectomy using a stapler and the role of regeneration of the residual splenic stump]. AB - Current evidence indicates that only complete or partial intact spleen can protect the organism against pneumococcal sepsis. What is not clear is the amount of minimal splenic tissue needed to protect the organism against such infection. This study has been carried out on 20 dogs which underwent partial or total splenectomy with stapler. Animals were divided into 8 groups according to the quantity of the remnant splenic tissue: 0% (4 dogs); 5% (4); 15% (1); 25% (1); 35% (2); 50% (2); 75% (2); 100% (4), and were followed up for 6 and 12 months. No mortality or bleeding was registered. Results showed a splenic regeneration, histologically demonstrated as an increased number of germinal follicles, in 12 out of 16 dogs, more evident in the animals sacrificed at one year. In conclusion, even a small amount (5%) of splenic tissue preserved with its blood supply can regenerate and acquire with time enough immunological function to protect the organism against post-splenectomy sepsis. PMID- 1873156 TI - [Low colorectal anastomosis using the Knight and Griffen technique]. AB - The low anterior resection currently represents the procedure of choice in the treatment of middle and low rectal cancer. The double stapling technique described by Knight and Griffen may be considered a safe and valid alternative able to decrease the incidence of complications related to a low colorectal anastomosis. PMID- 1873157 TI - [Therapy of massive anastomotic hemorrhage after anterior mechanical rectocolonic resection]. PMID- 1873158 TI - [Reconstructive possibilities in thoracic surgery. Our experience]. PMID- 1873159 TI - [Use of Premium CEEA in low anterior resection of the rectum]. PMID- 1873160 TI - [Lasers and mechanical staplers in surgery of the digestive system]. PMID- 1873161 TI - [Manual versus stapler anastomosis in colorectal surgery: a problem still open?]. PMID- 1873162 TI - [Repair of recurrent laparocele using intraperitoneal prosthesis]. PMID- 1873163 TI - [A simple, efficacious and economical method of plastic surgery of laparocele using local skin]. PMID- 1873164 TI - [Use of mechanical staplers in gastric resection]. PMID- 1873165 TI - [Controllable gastric banding as an alternative to vertical gastroplasty in the treatment of obesity]. PMID- 1873166 TI - [Continent gastrostomy using mechanical staplers]. PMID- 1873167 TI - [Mechanical sutures after extirpation surgery of the pancreas]. PMID- 1873168 TI - [Use of surgical staplers in surgery of the colon: personal experience]. PMID- 1873169 TI - [Termino-terminal choledocho-choledochal experimental microanastomosis using lasers]. PMID- 1873170 TI - [Reconstruction after total gastrectomy: an original technique]. PMID- 1873171 TI - [Use of surgical staplers in oncological colorectal surgery: why we perform latero-terminal anastomoses]. PMID- 1873172 TI - [Enlarged total gastrectomy in recurrence of adenocarcinoma of the gastric stump]. PMID- 1873173 TI - [Use of circular mechanical staplers in colostomy]. PMID- 1873174 TI - [Mechanical functional termino-terminal anastomosis in the treatment of Crohn disease]. PMID- 1873175 TI - [Methods of reconstruction of the alimentary tract after total gastrectomy: personal experience]. PMID- 1873176 TI - [Mechanical staplers in urinary diversion and orthotopic substitution of the bladder]. PMID- 1873177 TI - [Reconstruction techniques using surgical staplers after gastric resection]. PMID- 1873178 TI - [Proposal of a reconstruction method after total gastrectomy in prevention of entero-esophageal reflux]. PMID- 1873179 TI - [Duodenopancreatectomy and closure of the pancreatic stump using a surgical stapler. Preliminary results]. PMID- 1873180 TI - [Surgical staplers in lung surgery]. PMID- 1873181 TI - [Mechanical sutures in gastroesophageal surgery: usefulness and limits of our experience]. PMID- 1873182 TI - [Reconstruction after duodenopancreatectomy: pancreatico-jejunal anastomosis]. PMID- 1873183 TI - The role of mechanical sutures and devices in surgical teaching and training. PMID- 1873184 TI - [Carcinoma of the cervical esophagus. Problems of surgical technique]. AB - The tape shows the surgical technique used by the Authors for the alimentary tract reconstruction after total esophagectomy for cancer of the upper esophagus. A review of the main reconstructive techniques used for this disease is reported. PMID- 1873185 TI - [Comparison of mechanical and manual anastomoses in emergency gastric resection]. AB - Hundred and twenty-one patients underwent emergency subtotal gastrectomy for complications related to peptic ulcer (86) and malignant diseases (35). According to the type of anastomosis performed (manual or mechanical) patients were divided into two groups: 81 with hand-sutured anastomoses (double layer) and 40 with stapled anastomoses. The latter were more commonly used in the Roux-en-Y reconstruction and Billroth 1 gastrectomy. Median operating time (192' versus 190'), hospital stay (15.2 versus 13.5 days), postoperative complications (38% versus 32.5%) and anastomotic or duodenal stump leakage (7.4% versus 5%) showed no significant difference between groups. Therefore, in emergency subtotal gastrectomy mechanical anastomoses allow to obtain results comparable to the more used manual ones. PMID- 1873186 TI - [Anorectal sphincter function after mechanical anterior resection in cancer of the rectum]. AB - Out of a total of 365 operations for colo-rectal disease performed during the period 1980-1989 at the III and V Division of General Surgery of the 2nd Faculty of Medicine and Surgery of Naples, 181 (49.6%) patients had rectosigmoidal cancer: 95 (52.5%) underwent anterior resection and 86 (47.5%) Miles' operation. In 46 patients who underwent mechanical anterior resection during the period 1986 1989, pre and postoperative sphincter function was studied through a complete anamnesis, physical examination, sigmoidoscopy or colonoscopy and balloon manometry. All data were analyzed considering both the distance of the anastomosis from the anal verge and the patient age in order to stress possible relations with incontinence. The low incidence of incontinence registered after 12 months (6.5%), confirms the importance of manometry and rehabilitation, both necessary to improve the quality of life in old patients who undergo low anterior resection. PMID- 1873187 TI - [Reconstruction after pancreaticoduodenectomy for cancer: Whipple-Child vs Traverso-Longmire technique (a National questionnaire 1990 on data of 1,095 cases of surgery)]. AB - The Authors report the results of a National multicentric experience in 1.095 cases of pancreaticoduodenectomy for cancer. In order to evaluate the reliability of pyloric preservation mortality, morbidity, and functional results are discussed. PMID- 1873188 TI - [Use of mechanical staplers in Billroth II gastrectomy]. AB - Some considerations on the use of staplers, use currently classified as "elective" and "of convenience", are shown. The Author wishes a change in this classification especially for what elective subtotal gastrectomy is concerned. In fact, the use of staplers in subtotal gastrectomy for tumors of the pyloric antrum and for complicated ulcer assures considerable advantages in terms of quickness, safety and sterility. Finally, the Author describes in detail a Billroth II subtotal gastrectomy performed with staplers. PMID- 1873189 TI - [Mechanical staplers in orthotopic ileal neo-bladder using the Studer and Zingg method: our experience]. AB - Detubularized orthotopic low-pressure bladder substitute following radical cystoprostatectomy allows micturition per urethram and urinary continence. We performed the Studer and Zingg procedure with ileal reservoirs in 26 bladder cancer patients, using staplers in 11 cases. A reduced operating time and a low postoperative complication rate were observed in these cases. Furthermore, functional results were comparable to those obtained with manual sutures and lithiasis was never observed. PMID- 1873190 TI - [Telescopic termino-terminal pancreatico-jejunostomy after duodenopancreatectomy]. AB - The Authors report their experience in pancreatic stump management after pancreaticoduodenectomy. "Telescope" end-to-end pancreaticojejunostomy realized with some safe technical details represents a valid reconstructive procedure especially when the pancreatic remnant has a normal parenchyma without dilated duct. PMID- 1873191 TI - [Controversies about reconstruction after pancreatic resections in neoplasms of the periampullary area]. AB - Extended pancreatic resections have still a significative morbidity: this explains all the technical alternatives proposed to the Whipple procedure. Treatment of the pancreatic stump after cephalic resection and the need of gastric resection are particularly debated today. The Authors, together with a wide literature review, report their experience with 45 patients who underwent cephalic (28 cases), subtotal (4 cases) or total (13 cases) pancreatectomy. Telescope pancreaticojejunostomy showed overall satisfying results (7% of dehiscences), inducing the Authors to use it in all cases. The role of pyloric preservation as proposed by Traverso and Longmire, which strongly reduces nutritional sequelae of pancreatectomy without negative effects on oncological radicality, is emphasized. PMID- 1873192 TI - Global programme on AIDS. HIV and HBV transmission in the health care setting. PMID- 1873193 TI - AIDS and HIV infection in the WHO Western Pacific Region. PMID- 1873194 TI - Biologicals unit and expanded programme on immunization. WHO European region workshop on testing of DPT vaccine with emphasis on in vitro methods. PMID- 1873195 TI - Human rabies. PMID- 1873196 TI - Increased tryptase levels in suction-blister fluid from patients with urticaria. AB - The levels of tryptase in the suction-blister fluid from patients with chronic urticaria, urticaria pigmentosa, cholinergic urticaria, urticarial dermographism, prurigo of unknown origin, eczema, psoriasis, atopic dermatitis, and from healthy controls were studied. The blister fluid from controls contained up to 15 micrograms/l of tryptase, whereas that from patients with active urticaria contained greater than 50 micrograms/l. This study demonstrates that patients with urticaria have mast cells that readily release tryptase in both the lesional and non-lesional areas of skin. PMID- 1873197 TI - In-vivo effects of solar-simulated ultraviolet irradiation on antioxidant enzymes and lipid peroxidation in human epidermis. AB - The effects of solar-simulated UV-irradiation on the activity of antioxidant enzymes and the amount of diene conjugation were studied in human epidermis in vivo. A single dose of UV-irradiation was found to result in a transient reduction in superoxide dismutase activity and this was followed by increased amounts of conjugated diene double bonds, an index for oxidative stress. This suggests that in-vivo exposure of human epidermis to solar-simulated UV irradiation causes changes in the enzymic antioxidant defence system which, in turn, are accompanied by increased level of oxidative stress. PMID- 1873198 TI - The epidermal basement membrane in basal cell carcinoma: an immunohistochemical study. AB - An immunohistochemical study of basal cell carcinomas of varying histological type, using a panel of antibodies to constituents of the epidermal basement membrane, showed marked deficiencies in the expression of the antigens identified by the antibodies LH7.2, GB3 and G71. There was no correlation between loss of immunoreactivity to these antibodies and the histological features of the tumour. PMID- 1873199 TI - Nail is produced by the normal nail bed: a controversy resolved. AB - Nail thickness and mass (dry weight/unit surface area) of 21 toenails, removed from 19 patients after accidental injury, were measured over the mid point of the lunula, at the nail plate immediately distal to the lunula and at the distal end of the nail bed. Nail thickness increased from 43% of the final thickness over the mid-point of the lunula to 81% at its distal margin, the remaining increase in thickness being formed by the nail bed. The changes in nail mass were comparable. We conclude that ventral nail produced by the nail bed comprises about one-fifth of the terminal nail thickness and mass. PMID- 1873200 TI - Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis. AB - The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed. PMID- 1873201 TI - Changes in the elastic tissue of the non-sun-exposed skin of cigarette smokers. AB - Biopsies were taken from the upper and inner arm of 10 60-year-old male cigarette smokers and compared with 10 age-matched controls who were non-smokers. The mean relative area, number and thickness of the elastic fibres were significantly increased in the cigarette smokers compared to the controls. These results were confirmed using antibodies to elastin or the microfibrillar component of elastic tissue. In the smokers the broader and more fragmented elastic fibres in the skin were not as intensely stained as those of the non-smokers and the ultrastructural alterations of the elastic fibres were similar to those in solar elastosis. PMID- 1873203 TI - Etretinate and visual function: a 1-year follow-up study. AB - Concern has been expressed in the literature that the drug etretinate may be potentially retinotoxic. Four patients are reported who have received long-term treatment with etretinate and who have undergone detailed evaluation for the development of visual dysfunction over a 1-year period. Despite prolonged treatment and high total doses no evidence of ocular toxicity attributable to the drug was found in any of the patients. PMID- 1873202 TI - In-vivo epidermal nuclear reactions: a selective process. AB - Epidermal in-vivo nuclear reactions of IgG occur primarily in patients with mixed connective tissue disease or systemic lupus erythematosus and have been associated with high titres of circulating antibodies to ribonucleoprotein (RNP). This study was carried out to examine whether these epidermal nuclear reactions are true or simply an excision artefact. We observed the epidermal nuclear reactions for IgG only and not for other immunoglobulins in both in-vivo and in vitro organ-culture studies, despite the presence of antinuclear antibodies (ANA) of all immunoglobulin classes. The association of the in-vitro epidermal nuclear reactions with serum RNP antibodies, although not absolute was statistically significant. The absorption of the serum with extractable nuclear antigen (ENA) preparation diminished the nuclear reactivity on tissue explants. In addition, the penetration of ANA into the nuclei of skin explants was both time and temperature dependent and was inhibited by sodium azide and by oligomycin. We conclude that the epidermal nuclear staining reactions observed by direct immunofluorescence on skin biopsies is selective and that the penetration of IgG into the epidermal cell nuclei is an active process and not an artefact. PMID- 1873204 TI - Plasma levels of 8-methoxypsoralen following oral or bath-water treatment. AB - The plasma levels of 8-methoxypsoralen (8-MOP) were determined in 18 patients on PUVA treatment for their psoriasis and in two control volunteers. Seven of the patients were on oral therapy and 13 having bath treatment. The plasma levels of 8-MOP were determined up to 6 h after treatment and varied between less than 10 ng/ml and 360 ng/ml for the orally treated group, and in the bath-treatment group were all less than 10 ng/ml. PMID- 1873205 TI - The influence of the menstrual cycle and pregnancy on atopic dermatitis. AB - The prevalence of a premenstrual deterioration in the symptoms of atopic dermatitis, as determined by a postal questionnaire completed by 150 women, was 33%. There was a significant association between a premenstrual worsening of atopic dermatitis and the presence of the symptoms of the premenstrual syndrome (P less than 0.002). Pregnancy had an adverse effect on atopic dermatitis in the majority of cases (52%), usually starting in the first 20 weeks of gestation, although an appreciable proportion of women (24%) had improved during their pregnancy. PMID- 1873206 TI - The induction of epidermal ornithine decarboxylase following tape stripping is inhibited by a topical vitamin D3 analogue (MC903). AB - The efficacy of MC903, a vitamin D3 analogue, in reducing hyperproliferation as determined by levels of ornithine decarboxylase (ODC) was investigated in a double-blind study of 15 patients with chronic plaque psoriasis. The lesions of psoriasis were treated for 8 weeks with MC903 in one of two different cream bases or with a placebo cream. Biopsies were taken before and after treatment. In addition an uninvolved area of skin was treated during the last 3 weeks and this as well as control areas were then sellotape stripped and biopsied after 8 h. Clinical improvement was seen in eight out of 11 patients treated with MC903 but there was no reduction in the level of ODC in psoriatic lesions after 8 weeks of treatment. The levels of ODC in the tape-stripped uninvolved skin after 3 weeks of treatment with MC903 averaged 22.5 +/- 4.2 pmol/min/mg protein as compared to 58.6 +/- 12.6 pmol/min/mg protein (P = 0.004). The trauma-induced induction of ODC activity was markedly inhibited by the application of MC903. PMID- 1873207 TI - Lupus erythematosus profundus with partial C4 deficiency responding to thalidomide. AB - A female patient with disfiguring lupus erythematosus profundus (LEP) from the age of 13 years was found to have an isolated partial C4 deficiency, with reduced levels of both allotypes, C4A and C4B. A genetic basis for the hypocomplementaemia was confirmed by a family study of complement and HLA types which revealed heterozygous null alleles for C4A and C4B in the proband. Marked improvement in her cutaneous lesions occurred with thalidomide. PMID- 1873208 TI - Periarticular fibrous nodules in Lyme borreliosis. AB - Periarticular fibrous nodules have been described in patients with late-phase acrodermatitis chronica atrophicans (ACA) in the setting of Lyme borreliosis. We report the clinical and histopathological study of two patients with periarticular fibrous nodules and with Lyme borreliosis and discuss the relationship between these nodules and ACA. PMID- 1873209 TI - Localized pemphigoid shares the same target antigen as bullous pemphigoid. AB - A case of localized pemphigoid is described in which the lesions were only on the lower legs. Immunoblotting of the patients' serum reacted with a 240-kDa polypeptide identical to one of the bullous pemphigoid antigens. IgG1 was detected in the lesional skin and IgG1 and IgG4 in the patient's serum. These observations suggest that the immunopathological mechanisms in the blister formation in localized pemphigoid are similar to those found in more widespread bullous pemphigoid. PMID- 1873210 TI - Dermatomyositis responding to treatment of associated toxoplasmosis. AB - We report a 59-year-old woman with severe dermatomyositis in association with high serum toxoplasma antibody titres who was successfully treated with pyrimethamine and sulphadiazine. This case supports an aetiological role for toxoplasmosis in the pathogenesis of some cases of dermatomyositis. PMID- 1873211 TI - Tuberculosis verrucosa cutis in a tumour-like form. AB - An unusual case of tuberculosis verrucosa cutis that presented with a tumour-like lesion on the heel is described. This responded rapidly to treatment with isoniazid. PMID- 1873212 TI - Lupus erythematosus and hereditary angio-oedema. PMID- 1873214 TI - 71st annual meeting of the British Association of Dermatologists. London, 3-6 July 1991. Abstracts. PMID- 1873213 TI - Premenstrual exacerbation of nickel allergy. PMID- 1873215 TI - Immunoregulation by interleukin-4 in man. PMID- 1873216 TI - For debate: bone marrow transplantation for severe thalassaemia (1). The view from Pesaro (2). To be or not to be. PMID- 1873217 TI - BCNU treatment of marrow stromal monolayers reversibly alters haematopoiesis. AB - The marrow stromal microenvironment is essential for maintaining normal haematopoiesis. Chemotherapy drugs, such as the nitrosoureas, may impair the ability of the stroma to support haematopoiesis. To assess the effects of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) on in vitro haematopoiesis, stromal monolayers were treated with BCNU, 5 micrograms/ml weekly for 3 weeks, then seeded 24 h after the third treatment with haematopoietic progenitors. Three weeks after seeding, total adherent and non-adherent cell numbers were similar in treated and control flasks as were adherent granulocyte/macrophage colony forming cell (GM-CFC) numbers. In contrast, non-adherent GM-CFC were significantly reduced in treated flasks, to 40-60% of controls. However, no reduction in non adherent GM-CFC number was seen if seeding was delayed for 7 d following BCNU treatment, suggesting the effects are reversible. Conditioned media from treated and control monolayers, harvested at a time corresponding to the time of seeding, showed no difference in colony stimulating activity. In addition, extracts of bound growth factors from treated and control monolayers also showed no differences in colony stimulating activity. Thus, BCNU can alter haematopoiesis through a reversible effect on the marrow stroma and this effect does not appear to be mediated by a change in stromal growth factor production. PMID- 1873218 TI - The anti-mitozantrone monoclonal antibody NO-1, protects acute leukaemia cell lines from the cytotoxic effects of mitozantrone. AB - The monoclonal antibody NO-1 was raised against the potent anti-cancer drug mitozantrone by immunization of a BALB/c mouse with a mitozantrone-keyhole limpet haemocyanin conjugate in Freund's complete adjuvant. This antibody was shown to be highly effective in vitro at neutralizing the cytotoxic effects of mitozantrone for the acute leukaemia cell lines ALL-1 and MOLT4. In order to achieve complete protection, a drug to antibody molar ratio of 1.5:1 was required. The neutralizing effect was specific for mitozantrone, as NO-1 antibody offered no protection of the MOLT4 cell line to the cytotoxic effects of the anthracycline drug daunorubicin when used at a near identical molar ratio. NO-1 antibody has already proven a highly successful monoclonal reagent for use in a competitive enzyme-linked immunosorbent assay for the accurate and sensitive quantitation of mitozantrone in serum. The neutralizing properties of NO-1 suggest other possible applications for this antibody. These could include a use in the rapid clearance of pharmacologically active mitozantrone from the circulation following very high dose administration prior to bone marrow transplantation and for the construction of bispecific antibodies for targeting mitozantrone to tumour cell populations. PMID- 1873219 TI - Lymphohaematopoietic chimaerism after bone marrow transplantation for chronic myeloid leukaemia: results of simultaneous cytogenetic analyses on T-cell colonies, myeloid, and erythroid progenitor cells. AB - Various lymphohaematopoietic compartments represented by cells from T-cell colonies, myeloid progenitor cells (CFU-GM), erythroid progenitor cells (BFU-E), and bone marrow after short-term culture (BM) have simultaneously been analysed in 15 patients receiving 17 bone marrow transplants for Philadelphia chromosome (Ph) positive chronic myeloid leukaemia (CML) or acute lymphoblastic leukaemia (ALL). The marrow grafts were not T-cell depleted. Ten patients without relapse did not show any myeloid cells of host origin until their last follow-up or until death. However, in four of these patients single lymphoid host cells not carrying the Ph chromosome were found after BMT without clinical consequences. In patients with cytogenetic or haematological relapse Ph positive metaphases were first detected in any of the progenitor cell compartments along with residual donor cells in two of three patients. BM became Ph positive after various time intervals. Another patient with CML became Ph positive in all compartments investigated at the same time. The only patient with Ph positive ALL remained completely Ph negative also when haematological and clinical relapse was evident. All patients with relapse exhibited complex clonal and non-clonal chromosomal aberrations at the time of recurrence of the Ph chromosome. Such abnormalities not identical to those usually found with evolution of the disease and preferentially occurring in progenitor cells preceded the reappearance of Ph positive metaphases in one of our patients. PMID- 1873220 TI - Differential dose-related haematological effects of GM-CSF in pancytopenia: evidence supporting the advantage of low- over high-dose administration in selected patients. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional haematopoietin which can promote production of several blood cell lineages, though the predominant target cells are neutrophils, monocytes, and their precursors. Occasional undesirable clinical effects include eosinophilia, an increase in blasts, or thrombocytopenia. Here, we describe four patients who were treated with GM-CSF, at subcutaneous doses significantly lower than are conventional, and experienced an unusual response pattern. Three patients had severe pancytopenia associated with chronic lymphocytic leukaemia (CLL) or myelodysplastic syndrome (MDS) and exhibited an unexpected switch in the responsive lineage on high- versus very low-dose therapy. The two CLL patients developed marked eosinophilia (up to 10.0 x 10(9) cells/l) without an increase in neutrophils on 125-300 micrograms/m2/d of GM-CSF. In contrast, when the dose was lowered to 10 micrograms/m2/d, the neutrophils rose to physiological levels, without significant eosinophilia. The MDS patient showed a rapid rise in peripheral blasts (baseline level = 0; post-therapy level = 5.0 x 10(9)/l), without a change in other cell types, when receiving 60 micrograms/m2/d of GM CSF. After GM-CSF was held, blasts returned to baseline levels; reinstituting therapy at the very low dose of 6 micrograms/m2/d was followed by an increase in platelet counts from 50 to 185 x 10(9)/l with only a minor increase in blasts. The fourth patient, who suffered from severe aplastic anaemia complicated by recurrent gastrointestinal haemorrhage, was only treated with the low-dose regimen. He showed a predominant platelet effect with counts rising from 9 to 169 x 10(9)/l. Very low-dose GM-CSF therapy was devoid of constitutional side effects. The biological implications of these GM-CSF responses are discussed. Our results indicate that, in some patients, GM-CSF may stimulate different target cells depending on the dose. Therefore, in contrast to the results of administration of many classical drugs, there may not always be a direct relationship between the amount of GM-CSF given and the optimal effect. PMID- 1873221 TI - Haemophilia B mutations in a complete Swedish population sample: a test of new strategy for the genetic counselling of diseases with high mutational heterogeneity. AB - Carrier and prenatal diagnosis based on the identification of the gene defect (direct diagnosis) increases the proportion of haemophilia B families that can be offered precise genetic counselling from the 50-60% attainable by DNA markers, to 100% and they also provide information on the molecular biology of the disease. We propose that in order to maximize the practical and scientific benefits of direct diagnosis the gene defect of complete (possibly national) populations of patients should be characterized and the information stored in appropriate confidential databases. We demonstrate the feasibility of such a strategy by characterizing the mutations of all the patients registered with the Malmo haemophilia centre. These patients (44 male and 1 female) are from 45 unrelated families and 24 (53%) have negative family history. The 25 patients with similar reduction of factor IX:C and factor IX:Ag (24 male + 1 female) have: two gross deletions, three frameshifts, four translation stops, six mutations expected to affect pre-mRNA splicing and 10 amino acid substitutions. The six patients with greater reduction of factor IX:C than factor IX:Ag and the seven with reduced IX:C and normal IX:Ag have only amino acid substitutions. Patients with inhibitors have: one complete deletion, one frameshift and three translation stops. One patient has both a translation stop and a functionally neutral amino acid substitution (His257----Tyr). Characterization of the factor IX mutation was successful in every case, usually entailed 4 person-days work, and has led to the identification of 12 amino acid residues essential for the factor IX structure and function. PMID- 1873222 TI - An HphI-polymorphism in exon 28 of the von Willebrand factor gene, and its frequency among patients with various forms of von Willebrand's disease. AB - Besides having a large number of restriction fragment length polymorphisms (RFLP) the von Willebrand factor (vWF) gene contains several sequence polymorphisms in the coding regions. Eight nucleotide substitutions have been reported in two or more independent cDNA clones. Four of them give rise to amino acid substitutions, two of which are in the mature vWF subunit (at positions 26 and 709). We have investigated a previously suggested putative alanine-threonine polymorphism at position 618 of the mature subunit in normal subjects and patients with various types of von Willebrand's disease (vWD). the codon for amino acid 618 is located in exon 28, which encodes several important vWF functional domains. We amplified the whole exon 28 and parts of it by polymerase chain reaction (PCR) and distinguished gene from pseudogene sequences. The alanine----threonine (G----A) substitution was studied with restriction enzyme cleavage of the products, since it creates a new HphI site. Moreover, in two individuals we confirmed the polymorphism by cDNA sequencing. In 23 normals the frequencies of the h- (Ala) and the h+ (Thr) alleles were 0.50/0.50. In eight patients with type III vWD from seven different families, the h- allele was present in 13 of 16 genes, but whether this signifies a common mutation in some of the patients is not known. In types I and II, both alleles were present in roughly similar proportions. Owing to the high frequency of heterozygosity, the polymorphism should prove useful as an aid in genetic counselling. PMID- 1873223 TI - Novel point mutations leading to type 1 antithrombin deficiency and thrombosis. AB - Direct sequencing of antithrombin III (AT) gene fragments specifically amplified by the polymerase chain reaction was utilized to identify the molecular basis of type 1 AT deficiency in two unrelated kindreds, both with thrombotic disease. Two novel point mutations were identified, deletion of a T from the second position of codon 81 in one propositus and insertion of a G in codon 424 in the second kindred. The AT 81(-T) frameshift mutation leads to a premature stop signal in codon 89, while the AT 424(+G) allele has a premature stop only one codon short of the normal gene. The latter mutation changes the eight carboxy terminal residues of AT, including 429Cys, and increases the proportion of polar amino acids in this region. We suggest that altered folding of the mutant protein may explain the AT deficiency. PMID- 1873224 TI - Molecular basis for hereditary antithrombin III quantitative deficiencies: a stop codon in exon IIIa and a frameshift in exon VI. AB - Antithrombin III (AT III) is an inhibitor of serine protease (serpin) comprising 432 amino acids. Quantitative AT III deficiencies are associated with a high risk of thrombotic disease. Although this risk is smaller in patients with qualitative AT III deficiencies, the molecular defects characterizing the latter have been the subject of many studies. However, in quantitative AT III deficiencies, only three mutations have been described: Pro 407 to Leu and A1a404 to Thr (both located in the C-terminal part of the AT III molecule) and also a frameshift in exon IIIa. Using the asymmetric polymerase chain reaction (PCR) and genomic DNA analysis by direct sequencing, we detected two mutations in three unrelated families: (i) a C----T transition in exon IIIa in two families, leading to the replacement of the codon corresponding to Arg 129 by a stop codon, and (ii) in the third family, insertion of an adenine in the codon corresponding to Phe 408, a highly conserved serpin amino acid. This insertion altered the reading frame and led to the appearance of a premature stop signal. Patients of all three families were heterozygous for their abnormality. These results show that asymmetric PCR and genomic DNA analysis by direct sequencing permit fast identification of the molecular basis of quantitative AT III deficiencies. It is concluded that in many cases the absence of AT III gene product probably results from point mutation, as previously observed for another serpin, alpha-1 antitrypsin. PMID- 1873225 TI - Prothrombin fragment 1 + 2, thrombin-antithrombin III complexes and D-dimers in acute deep vein thrombosis: effects of heparin treatment. AB - Plasma levels of prothrombin fragment 1 + 2 (F 1 + 2), of thrombin-antithrombin III complexes (TAT) and of D-dimers were evaluated at several time intervals in 15 patients affected by acute proximal deep vein thrombosis, complicated or not by pulmonary embolism, and treated by conventional heparin therapy for 9 d. The mean levels of the three markers remained significantly increased throughout the period of observation, except for F 1 + 2 on day 9, when compared to normal values established in a population of normal healthy blood donors. However, whereas heparin significantly decreased the plasma levels of F 1 + 2 and of TAT complexes in less than 3 d. D-dimer levels were not significantly altered. Significant correlations were observed between the plasma levels of the three markers but they were not correlated to the actual intensity of heparin treatment evaluated as the activated partial thromboplastin time prolongation. These results indicate that heparin improves the hypercoagulable state associated with a deep vein thrombosis within the first days of treatment as indicated by TAT and F 1 + 2. They also account for the performances of D-dimer assay for the diagnosis of deep vein thrombosis in patients already receiving heparin, a common situation in routine hospital practice. PMID- 1873226 TI - HPA-5b (Br(a)) neonatal alloimmune thrombocytopenia: clinical and immunological analysis of 39 cases. AB - Maternal alloimmunization against fetal platelets can cause fetal and neonatal thrombocytopenia (NAIT). The HPA-1a (PIA1, Zwa) antigen is by far the most common antigen implicated in NAIT. However, today another antigen often linked with that affection is HPA-5b (Br(a)). This is a report of 39 cases of NAIT involving the HPA-5b antigen. Thrombocytopenia may be of grave consequence. Three infants developed intracerebral haemorrhages (ICH). Of these, one died presumably as a consequence of ICH. Central nervous system (CNS) sequelae in the neonatal period was observed in two children. The potential hazards of death or disabling neurologic sequelae following intracerebral haemorrhage call for rapid and reliable diagnosis and effective therapy. Because there is high risk that subsequent pregnancies might be also affected by NAIT, the mothers of a previously affected child should be managed similarly to the HPA-1b mothers (PIA2, Zwb). The antenatal diagnosis of thrombocytopenia should be made and if necessary the in utero therapy instituted. PMID- 1873227 TI - A novel delta 0 mutation in cis with Hb Knossos: a study of different genetic interactions in three Egyptian families. AB - We have defined the molecular basis of normal HbA2 beta-thalassaemia associated with Hb Knossos. DNA sequence analysis of the delta globin gene in cis with beta Knossos showed deletion of a single A in codon 59 leading to a premature termination at codon 60. This delta 0/beta Knossos allele has been observed in three unrelated Egyptian families and associated with a single beta haplotype (+- --++). One individual who was homozygous for the delta 0/beta Knossos allele as well as heterozygous for a non-deletional alpha thalassaemia, was completely clinically asymptomatic, while others have coinherited the delta 0/beta Knossos allele with different beta and alpha thalassaemia determinants. A study of the different genetic interactions giving rise to a spectrum of clinical phenotypes is reported. PMID- 1873228 TI - Abnormal neutrophil adhesion in sickle cell anaemia and crisis: relationship to blood rheology. AB - Defects in neutrophil adhesion and migration may contribute to the susceptibility to infection seen in sickle cell anaemia (SCA). These dynamic defects may be influenced by abnormalities in blood rheology found in this disorder. A whole blood model was used to study neutrophil adhesion in SCA patients: neutrophil adhesion to protein coated glass was quantitated by measuring the rate of disappearance of neutrophils from heparinized whole blood circulating through a perfusion chamber. Twenty-three adult patients (Hb SS) were studied in asymptomatic steady state, of whom nine were also studied during pain crisis, both before and 4-7 d after conventional therapy. Red cell and granulocyte filterability and whole blood and plasma viscosity were also measured. The half time for disappearance from the perfusion system (t1/2) of neutrophils from patients in the steady-state was 93.5 +/- 8.4 min, compared to 49.1 +/- 2.8 min in normal age-matched controls (P = 0.001). In crisis t1/2 was further prolonged to 170.0 +/- 16.1 min (P = 0.01 v. steady state). After therapy, t1/2 decreased to 57.0 +/- 4.5 min (P = 0.001 v. pre-therapy state and P = 0.009 v. steady state) and was comparable to Hb AA controls. These findings reveal a neutrophil adhesion defect in SCA which worsens in crisis but is corrected following supportive therapy. Red cell filterability (expressed as average resistance to flow and pore-clogging particles) and white cell filterability (expressed as pore clogging particles) were also abnormal in SCA and were found to correlate with neutrophil adhesion. Plasma viscosity also correlated with adhesion t1/2. The defect appears to be related to abnormal blood flow properties in SCA but the rheological factors cannot fully explain either the steady-state defect or the marked changes in neutrophil adhesion during crisis. PMID- 1873229 TI - Production of soluble transferrin receptor by K562 erythroleukaemia cells. AB - The present study was undertaken to examine the production of soluble transferrin receptor by K562 erythroleukaemia cells under controlled experimental conditions. The concentrations of soluble and cellular transferrin receptor were measured by immunoassay employing monoclonal antibodies. Cellular ferritin was also measured as an index of iron supply. With incubation up to 48 h there was a progressive increase in the concentration of soluble transferrin receptor. Manipulating iron supply by adding iron chelators or diferric transferrin to the incubation medium produced marked alterations in cellular receptor and ferritin content. Under all such conditions examined, the relationship between soluble and cellular receptor remained highly constant. These findings support clinical studies of serum receptor suggesting that over a broad spectrum of haematological disorders there is a fixed relationship between serum receptor and tissue receptor mass. PMID- 1873230 TI - A case of chronic idiopathic thrombocytopenic purpura with a high titre of platelet membrane-associated antiphospholipid antibodies. PMID- 1873231 TI - Philadelphia chromosome in a sarcoidosis patient? PMID- 1873232 TI - Dapsone for idiopathic autoimmune thrombocytopenic purpura in elderly patients. PMID- 1873233 TI - Prolonged recombinant activated factor VII (rFVIIa) treatment for severe bleeding in a factor-IX-deficient patient with an inhibitor. PMID- 1873234 TI - Interferon alpha-2b therapy in refractory adult chronic thrombocytopenic purpura. PMID- 1873235 TI - Anti-interferon antibodies in alpha interferon treated patients with chronic myeloid leukaemia. PMID- 1873236 TI - First report of a cardiac transplantation in a patient with thalassaemia major. PMID- 1873237 TI - Annotated bibliography of structural equation modelling: technical work. AB - Researchers must be familiar with a variety of source literature to facilitate the informed use of structural equation modelling. Knowledge can be acquired through the study of an expanding literature found in a diverse set of publishing forums. We propose that structural equation modelling publications can be roughly classified into two groups: (a) technical and (b) substantive applications. Technical materials focus on the procedures rather than substantive conclusions derived from applications. The focus of this article is the former category; included are foundational/major contributions, minor contributions, critical and evaluative reviews, integrations, simulations and computer applications, precursor and historical material, and pedagogical textbooks. After a brief introduction, we annotate 294 articles in the technical category dating back to Sewall Wright (1921). PMID- 1873238 TI - Management of the pregnant woman with spinal cord injuries. AB - This paper forms part of an ongoing prospective study of pregnancy and labour in women with spinal cord injuries and combines a prospective and retrospective analysis of 17 pregnancies in 15 women with spinal injuries. The management and outcome in those 17 pregnancies is reviewed. PMID- 1873239 TI - How does the mode of delivery affect the cost of maternity care? AB - In this paper we present estimates of the difference in the cost of hospital care for women having different modes of singleton delivery. The estimates are based on observation of resources used in different procedures, and on data from the North West Thames Region Maternity Information System. For vaginal delivery the average cost is 363 pounds, but could fall between 189 pounds and 773 pounds, and for caesarean section the average cost is 1123 pounds, with a likely range from 837 pounds to 1560 pounds. The wide ranges in the costs of the two modes of delivery reflect variation in the length of stay and in the intensity of care required. The average cost for intrapartum care and postnatal stay is estimated to be 451 pounds for all singleton births. Variation in operative delivery rates between hospitals implies differences in the overall cost of care at different maternity units. This partly reflects differences in the needs of the population served by the units, but also differences in clinical practice. It is important for decision makers to consider the balance between the costs and outcomes of different policies of care. PMID- 1873240 TI - Head circumference/abdominal circumference ratio, ponderal index and fetal malnutrition. Should head circumference/abdominal circumference ratio be abandoned? AB - Head circumference/abdominal circumference (HC/AC) ratios of the fetus are accepted as a means of distinguishing different patterns of growth retardation with a high ratio implying malnutrition of the fetus. Ponderal index (birthweight/length3) is used by paediatricians as a measure of neonatal wasting and would therefore be expected to correlate with HC/AC ratios at delivery. Anthropometric data on 999 newborn infants have been collected and analyzed by multiple regression. The results show a poor correlation between ponderal index and HC/AC ratio, worse than that between ponderal index and AC alone. The use of HC/AC ratios antenatally to identify subgroups of intrauterine malnutrition should be abandoned. The prediction of intrauterine malnutrition by weight/length ratios should be investigated further. PMID- 1873241 TI - A randomized comparison of oxytocin, sulprostone and placebo in the management of the third stage of labour. AB - OBJECTIVE: To compare the effect on post partum bloodloss of the postpartum prophylactic administration of oxytocin or sulprostone in low risk women having an expectant management of the third stage. DESIGN: Randomized, placebo controlled, double-blind trial. SETTING: Radboud University Hospital, Nijmegen (67 women) and Lievensberg Hospital, Bergen op Zoom (10 women). PARTICIPANTS: 77 women entered the trial (three were excluded). INTERVENTIONS: The intramuscular injection, immediately after the birth of the baby, of either oxytocin 5 IU, sulprostone 500 micrograms or 0.9% saline. MAIN OUTCOME MEASURES: Quantitative postpartum blood loss and length of third stage. RESULTS: Postpartum blood loss was reduced almost equally, by about 35%, by oxytocin (P = 0.02), or sulprostone (P = 0.05). The mean length of the third stage was shorter in both groups receiving the active treatment, this effect was significant in the sulprostone group (P = 0.01). CONCLUSION: Prophylactic administration of oxytocin or sulprostone directly after delivery followed by expectant management of the third stage reduces post partum blood loss and shortens the third stage. PMID- 1873242 TI - How obstetricians manage the problem of preterm delivery with special reference to the preterm breech. AB - A questionnaire regarding the route of birth for the preterm fetus with particular reference to the management of the preterm breech was sent to 180 consultants in England and Wales. Only 23% of respondents use electronic fetal monitoring below 26 weeks gestation and only 12% use caesarean section routinely for fetal indications at less than 26 weeks. Only 12% will use caesarean section for the preterm fetus presenting by the vertex in uncomplicated labour. Only 35% of all respondents consider that there is sufficient evidence to support the use of caesarean section for the uncomplicated preterm breech, but 76% will actually use caesarean section for this indication. Overall 71% reported that they are affected by medicolegal considerations in their management of the preterm breech. Overall, 83% said that they might change their practice regarding the mode of delivery of the preterm breech in the light of the findings of a randomized prospective controlled trial. PMID- 1873243 TI - Trends in multiple births in Italy: 1955-1983. AB - On the basis of the numbers of single and multiple births routinely collected by the Central Institute of Statistics, trends in multiple births in Italy over the period 1955-1983 were analyzed. Between 1955 and 1983 the frequency of multiple births declined by about 25% (from 12.6/1000 deliveries to 9.6/1000 deliveries). The downward trend was constant until the early 1970s when rates tended to level off and increase slightly. This finding was largely attributable to trends in dizygotic rates, monozygotic births being approximately constant over the period considered. Multiple birth rates rose till age 35-39, being more than two times higher in this age group than in teenagers, but flattened off in the subsequent strata of age: this finding was constant over the period considered. Despite the general decreasing trend, the regional differences persisted largely unchanged, multiple birth rates being about 30% higher in Southern (and less developed areas) of the country than in the North of Italy. Geographic differences were limited to dizygotic pregnancies, monozygotic rates being constant (about 4/1000 pregnancies) in various areas. PMID- 1873244 TI - Serum bile acids in normal pregnancy. AB - Serum bile acid levels were measured in a longitudinal study of 56 women throughout normal pregnancy. Postprandial levels of serum bile acids were measured at each visit. Mean serum bile acid levels increased significantly from 5.3 (2 SD 3.4) mumol/l at 16 weeks to 6.5 (2 SD 3.7) mumol/l at term (P less than 0.005). PMID- 1873245 TI - Menstrual symptoms in women with pelvic endometriosis. AB - OBJECTIVE: To investigate menstrual symptoms in relation to pelvic pathology. DESIGN: A prospective questionnaire-based study. SETTING: Aberdeen Royal Infirmary, Scotland. SUBJECTS: 1250 questionnaires were sent out prior to planned admission and 1200 women (96%) brought the completed questionnaires. They comprised 598 women undergoing laparoscopic sterilization, 312 having laparoscopy because of infertility, 156 having laparoscopy because of chronic pelvic pain and 134 women undergoing abdominal hysterectomy for dysfunctional uterine bleeding. MAIN OUTCOME MEASURES: The occurrence of dysmenorrhoea, menorrhagia, menstrual regularity, premenstrual spotting, deep dyspareunia and pelvic pain in women with either endometriosis and post infective pelvic adhesions or a normal pelvis. RESULTS: Menorrhagia, menstrual irregularity and premenstrual spotting occurred with equal frequency in all groups. Deep dyspareunia, pain after intercourse and recurrent pain unrelated to menstruation or coitus was more common in women with endometriosis and those with post infective pelvic adhesions than in those with a normal pelvis. Dysmenorrhoea appears to be more prevalent among women having endometriosis. CONCLUSIONS: Menstrual symptoms, while raising a high index of suspicion for endometriosis, are not entirely reliable as indicators of disease. Dysmenorrhoea is the most common reported symptom in endometriosis sufferers. Diagnostic laparoscopy should be considered before institution of treatment in women complaining of pelvic pain and menstrual symptoms. PMID- 1873246 TI - Experience with tissue expansion vaginoplasty. AB - In vaginal agenesis, a vagina can be treated by tissue expansion vaginoplasty. We have performed 17 such procedures. One procedure was abandoned because of infection of the temporary implant. In four women the first stage had to be repeated: in one the implant was placed too superficially, in another it did not provide adequate expansion, in a further instance the implant became infected and the fourth woman received a surgical wound to her labia. The second stage was successful in all 16 women who now have a vagina lined with viable epithelium. The vaginal length was satisfactory in all but one. Two women complained of a vaginal discharge due to hair at the vaginal vault, two women developed postoperative haematomas and one experienced introital stenosis. The disadvantage of the procedure is that it requires two operative stages and involves a prolonged hospital stay but it is not technically complex and results in a full length vagina that does not require dilatation. PMID- 1873247 TI - Crouching over the toilet seat: prevalence among British gynaecological outpatients and its effect upon micturition. AB - This study investigated whether British women prefer to crouch over public toilet seats, and measured the effect of such a voiding position on urine flow rate and residual urine volume. Of 528 consecutive women who attended a general gynaecological clinic and completed an anonymous questionnaire, 85% usually crouched over the toilet when using a public convenience, 12% applied paper to the seat and 2% sat directly on public toilet seats. When using a friend's bathroom 38% of the women voided by crouching. Results were similar for 155 patients attending a urodynamic clinic, 80 of whom were studied while voiding in both positions. There was a 21% reduction in average urine flow rate and a 149% increase in residual urine volume in the crouching position. Women undergoing urodynamic tests should be asked which voiding position they used before abnormal results are interpreted. Patients with a reduced functional bladder capacity may benefit from being encouraged to sit comfortably on the toilet whenever possible. PMID- 1873248 TI - Oocyte and follicular fluid characteristics in women with mild endometriosis. AB - The follicular development, fertilization and cleavage rates and follicular fluid endocrinology were assessed in 20 women with mild endometriosis during a spontaneous menstrual cycle. Diagnostic laparoscopy was performed 32 h after the onset of the endogenous luteinizing hormone (LH) surge in the 20 women with laparoscopically confirmed mild endometriosis and in a control group of ten women with tubal infertility. There was no significant difference in oocyte maturity or fertilization and cleavage rates between the women with mild endometriosis and those in the control group. The endocrine milieu of the pre-ovulatory oocyte at the time of aspiration was similar in the two groups. PMID- 1873249 TI - Immunoreactive endometritis. AB - A benign polyclonal lymphoid proliferation of the endometrium which bears morphological resemblance to the malignant lymphoma is found among women with bleeding disturbances. Seven previous cases have so far been reported in the literature. A retrospective examination of 11,648 endometrial specimens revealed 287 examples of chronic endometritis (2.5%) of which 29 displayed lymphoid proliferation. We found no evidence of malignant haematologic disorder after a median observation of 68 months and no positive association with prior or present infectious disease. Histological follow-up of ten patients showed that changes could persist for up to 12 months. We name this benign condition 'immunoreactive endometritis'. PMID- 1873250 TI - Acute recurrent polyhydramnios--management with indomethacin. PMID- 1873251 TI - Vulvodynia and selective IgA deficiency. Case reports. PMID- 1873252 TI - Placenta accreta and myotonic dystrophy. Two case reports. PMID- 1873253 TI - Ovarian necrotizing vasculitis causing major intra-abdominal haemorrhage after IVF. Case report and literature review. PMID- 1873254 TI - Imaging of pulmonary endometriosis by immunoscintigraphy. Case report. PMID- 1873255 TI - Raised serum CA 125 preceding the diagnosis of carcinoma of the fallopian tube: two case reports. PMID- 1873256 TI - Pre-eclampsia and anti-phospholipid antibody. PMID- 1873257 TI - Hormone implants and tachyphylaxis. PMID- 1873258 TI - The clinical presentation of women with human immunodeficiency virus infection. PMID- 1873259 TI - Vulval reconstruction by free tissue transfer. PMID- 1873260 TI - Acute retinal necrosis. PMID- 1873261 TI - Factors associated with poor visual outcome in acute retinal necrosis. AB - We reviewed 22 consecutive patients (26 eyes) with acute retinal necrosis to elucidate whether there was any sign at an early stage to predict poor visual outcome. Final visual acuity of the patients fell into two groups, one worse than 20/600 (15 eyes) and the other better than 20/30 (11 eyes). The patients with poor visual outcome showed diffuse retinal arteritis or arterial obliteration which was associated with reduced amplitude of electroretinographic a and b waves and elevated levels of circulating immune complex, even at an early stage when retinal exudates were still localised to the peripheral fundus. The retinal exudates in these patients extended rapidly to the posterior pole. In contrast, the patients with good visual outcome showed retinal arteritis limited within retinal exudates throughout the course. These signs at an early stage can be used as prognostic factors to manage patients with acute retinal necrosis more constructively. PMID- 1873262 TI - Surgical management of retinal detachment associated with the acute retinal necrosis syndrome. AB - We operated on nine eyes in eight patients with retinal detachment associated with acute retinal necrosis (ARN) syndrome. The patients were treated with scleral buckling, vitreoretinal surgery, or a combination of these treatments. Vitrectomised eyes underwent combinations of lensectomy, membrane dissection, scleral buckling, air-fluid exchange, endolaser photocoagulation, cryotherapy, and retinal tamponade with C3F8 gas or SF6 gas. Macular attachment was achieved in eight (89%) eyes. Vision improved in seven (78%) eyes, of which five (56%) achieved 20/200 or better vision. Three eyes that had received laser treatment posterior to areas of retinitis suffered retinal detachment despite this prophylactic treatment. Poor visual outcome resulted from viral infection of the optic nerve or macular involvement, macular hole formation, macular pucker, or hypotony. PMID- 1873263 TI - Retinal circulation times in diabetes mellitus type 1. AB - Video fluorescein angiography was performed in 124 patients between 18 and 65 years of age (mean 35.0, SD 12.3 years) with juvenile-onset, insulin-dependent diabetes mellitus (type 1). The arm-retina time (ART) and the retinal arteriovenous passage time (AVP) were measured by means of a picture analysis system to quantify the retinal microcirculation. Glucose metabolism was assessed by the blood level of haemoglobin A1c. The ART 11.5, SD 3.4 s) was similar to that in normal persons (11.2, SD 3.3 s), while the AVP was significantly longer in the diabetics (AVP = 2.35, SD 0.87 s) than in normal persons (AVP = 1.45, SD 0.40 s). The patients with severe diabetic retinopathy showed the most impressive change in AVP. The diabetics with good glycaemic control, that is, with glycosylated haemoglobin (HbA1c) less than or equal to 8.0 g/dl, had a shorter AVP than patients with bad glycaemic control (HbA1c greater than or equal to 9.5 g/dl). The group with a history of diabetes for less than five years showed circulation parameters similar to those of normal persons. The AVP in this group was significantly shorter than in groups with a history of diabetes for five or more years. PMID- 1873264 TI - Pulsatile ocular blood flow in patients with low tension glaucoma. AB - Measurements of the intraocular pressure (IOP) pulse and pulsatile ocular blood flow (POBF) have been made in 22 patients with bilateral low tension glaucoma (LTG) and 29 healthy subjects matched as closely as possible for age, refractive error, IOP, systemic pulse pressure, and heart rate. Recordings were made in both the standing and supine positions. The amplitude of the intraocular pressure pulse was significantly lower in patients with LTG (1.2, SEM 0.1 mmHg standing, and 1.3, SEM 0.1 mmHg lying) than in healthy subjects (1.9, SEM 0.1 mmHg standing, and 2.0 SEM 0.1 mmHg lying): p less than 0.001 standing and p less than 0.002 lying. Measurement of POBF also showed a significant reduction between the healthy subjects (428 (31) SEM microliters/min standing and 345 (28) SEM microliters/min lying) and subjects with LTG (301 (27) SEM microliters/min standing and 249 (24) SEM microliters/min lying), p less than 0.005 standing and p less than 0.02 lying. This represents a difference of approximately 30% between the two groups in either posture. A close non-parametric correlation existed between the level of IOP and the POBF (r = 0.75, p less than 0.001 standing, and r = -0.55, p less than 0.02 lying). Such a correlation was not present in the healthy subjects. A reduction in POBF occurred in both groups on assuming the supine posture (healthy subjects 83 (16) SEM microliters/min, LTG subjects 52 (17) SEM microliters/min). These figures represent reductions of 19% and 17% respectively in comparison with the standing value. The results lend further confirmation to the hypothesis that vascular factors are associated with low tension glaucoma. PMID- 1873265 TI - Complete infarction of the eye complicating a choroidal malignant melanoma. AB - Infarction of malignant melanoma of the choroid has been previously reported, but infarction of the whole eye in association with infarction of melanoma is a rare event that has not been previously described. We present such a case and discuss the possible pathogenesis. PMID- 1873266 TI - Comparison of the effects of intraocular irrigating solutions on the corneal endothelium in intraocular lens implantation. AB - We conducted a randomised prospective controlled study to determine the effects of a glucose glutathione bicarbonate solution (BSS Plus) and a citrate acetate bicarbonate solution (S-MA2) on the corneal endothelium in patients undergoing extracapsular cataract extraction with posterior chamber lens implantation. One eye of each patient was randomly assigned to receive BSS Plus, and the other eye to receive S-MA2. BSS Plus caused significantly less corneal swelling on the first postoperative day than did S-MA2. There was no difference between the two solutions in their effect on corneal thickness one week and one month postoperatively. Computer assisted morphometric analysis of wide-field specular microscopic photographs demonstrated minimal changes in endothelial morphological characteristics in the eyes irrigated with BSS Plus. By comparison S-MA2, caused a significant loss of endothelial cells and a marked reduction in the figure coefficient. These results indicated that BSS Plus has a clinical advantage over S-MA2 with respect to the corneal endothelium. PMID- 1873267 TI - Eyedrop instillation for reluctant children. AB - Pupillary responses to pilocarpine eyedrops applied by different techniques have been studied in healthy volunteer subjects. In particular a novel method was evaluated in which eyedrops were applied to the inner canthus with eyes tightly closed and the subject supine, followed immediately by opening of the eyes. The response to this technique indicates that drug penetration into the eye was 66% (confidence intervals 28 to 104%) of that obtained by conventional instillation, into the conjunctival sac, with or without 2 min pressure on the inner canthus. This method of instillation, which is free of aggravation, may be clinically useful for patients, especially children, unwilling or unable to tolerate conventional instillation. PMID- 1873268 TI - Ocutome lensectomy: results and complications. AB - We describe the results and the complications encountered in 69 lensectomies performed via a limbal approach with the Ocutome vitrectomy instrument, in which it was the intention at surgery to maintain the integrity of the posterior capsule. After operation 87% improved in visual acuity, and 68% achieved 6/12 or better. The main early complications encountered were perioperative rupture of the posterior capsule and iris damage. The main late complications were postoperative thickening of the posterior capsule, retinal detachment, and bullous keratopathy. Of the eyes in which the posterior capsule remained intact after operation 17% developed thickening of the posterior capsule to a degree that required capsulotomy over a mean follow-up period of 50 months. PMID- 1873269 TI - Surgical management of essential blepharospasm. AB - We have reviewed the surgical management of essential blepharospasm over the last 15 years, comparing the results from facial nerve avulsion with those from orbicularis muscle stripping. After facial nerve avulsion 50% of patients remained free of troublesome spasm for 15 months after surgery, but only 25% remained so for more than two years. Following orbicularis oculi myectomy 50% of patients were free of troublesome spasms for 30 months after surgery and 55% of patients had relief from spasm for more than two years. Secondary effects of the two procedures are compared and are found to be fewer after orbicularis myectomy. There were no major complications after either form of surgery. Botulinum toxin is the treatment of first choice for this condition. If this becomes ineffective or inconvenient, surgical treatment is warranted and should not be deferred for fear of severe side effects of treatment, since these are rare. Protractor myectomy gives longer relief from blepharospasm than facial nerve avulsion and has fewer complications. However, it is technically difficult, time consuming, and has greater peroperative morbidity. Facial nerve avulsion may therefore still have a role in selected patients. PMID- 1873270 TI - Fine needle aspiration biopsy in orbital tumours. AB - Fine needle aspiration biopsy (FNAB) was performed in 46 patients with an orbital mass. Positive cytological identification was made in 43 biopsy specimens. In 26 cases with histopathological control the accuracy was 81%. In experienced hands FNAB is safe and appears to be a valuable tool in establishing a diagnosis of malignancy in orbital tumours. PMID- 1873272 TI - Self-inflicted eye injuries. AB - Five cases of self-inflicted eye injury are described and discussed. A review of the literature shows that several psychiatric diagnoses have been assigned to people who damage their eyes. A variety of mechanisms to explain this phenomenon are described. PMID- 1873271 TI - Regression analysis of visual field progression in low tension glaucoma. AB - Eighty four patients (168 eyes) with low tension glaucoma were retrospectively reviewed (mean follow-up was 28 months). The mean age was 66 years, and 69% were females. Regression analysis of their automated Humphrey fields (a mean of eight fields per eye) showed progression in 50% of patients and in 37% of eyes. There was no statistically significant difference between patients with progression and non-progression with respect to age (p less than 0.05) or intraocular pressure (p less than 0.5). Visual field defects were located most frequently in the superior hemifield in both groups of patients. A considerable proportion of patients had advanced field loss at the time of diagnosis. PMID- 1873273 TI - Transpalpebral extrusion of a silicone sponge exoplant. AB - We report an unusual case of scleral buckle extrusion in a 63-year-old woman. A 5 mm silicone sponge exoplant eroded through Tenon's capsule, conjunctiva, and full thickness upper eyelid, traversing the tarsal plate. PMID- 1873274 TI - Nd-YAG laser hyaloidotomy for malignant glaucoma following one-piece 7 mm intraocular lens implantation. AB - Three cases of malignant glaucoma following extracapsular cataract extraction with 7 mm one-piece posterior chamber intraocular lens implantation are presented. Nd-YAG laser hyaloidotomy was successfully performed in all eyes, but was difficult and required several sessions in two eyes. In the third eye, which had a sector iridectomy, laser hyaloidotomy applied over the edge of the lens optic through the iridectomy resulted in brisk deepening of the anterior chamber and reduction of intraocular pressure. We propose that the one-piece 7 mm optic posterior chamber intraocular lens may constitute an obstacle to successful hyaloidotomy, mainly owing to its large size, as it may block aqueous percolation from the vitreous into the anterior chamber. Eyes prone to develop malignant glaucoma after surgery should have a sector or large peripheral iridectomy to facilitate postoperative Nd-YAG laser hyaloidotomy if required. PMID- 1873275 TI - Perforation of the globe--a complication of peribulbar anaesthesia. AB - Peribulbar anaesthesia has been recommended as a safer alternative to retrobulbar anaesthesia. We report a case of perforation of the globe sustained during peribulbar anaesthesia which resulted in blindness. Orbital injections are potentially dangerous, be they peribulbar or retrobulbar. To minimise the risk, short, blunt needles are advocated for the peribulbar route. PMID- 1873276 TI - Preserved action of a rectus muscle after transection by an encircling solid silicone band. AB - We present a case of anterior migration of a solid silicone band through a lateral rectus muscle. In this patient the action of the lateral rectus was preserved, and this is demonstrated photographically. The possible reasons for this rare complication and the possible mechanism by which lateral rectus activity remained intact are explained. PMID- 1873277 TI - Bilateral simultaneous spontaneous acute angle closure glaucoma in a herpes zoster patient. PMID- 1873278 TI - The association of Fuch's corneal endothelial dystrophy with angle closure glaucoma. PMID- 1873279 TI - Topical beta blockers and serum lipoproteins. PMID- 1873280 TI - Paget's disease and angioid streaks: one complication less? PMID- 1873282 TI - Trigeminal neuralgia--treatment of the third division by radiologically controlled cryoblockade of the inferior dental nerve at the mandibular lingula: a study of 31 cases. AB - Cryoblockade of the peripheral nerve affected by trigeminal neuralgia is an established technique for treatment. Freezing the inferior dental nerve using C arm image-intensification control, and a nerve stimulator to guide the slim Spembly Lloyd probe, offers an additional technique for treatment of a small number of patients with trigeminal neuralgia. This paper reports the results of 31 cryoblockades of the inferior dental nerve in 11 patients. PMID- 1873281 TI - Blood flow in jaw bones affected by chronic osteomyelitis. AB - In order to study circulatory changes throughout the course of chronic osteomyelitis of the jaws, blood flow in bone affected by osteomyelitis was assessed in 14 patients, by means of laser Doppler flowmetry (LDF). The difference in perfusion between the osteomyelitic bone and corresponding sites on the opposite healthy jaw was evaluated. The patients were classified into two groups according to the clinical activity of their disease. A significantly reduced bone blood flow was recorded in the jaw during non-active stages, while an increased flow was associated with the initial stage of disease and the inflammatory exacerbations. No pre-existing vascular disorders were discovered prior to the development of this disease. However, a long standing local inflammation of the jaw bone was associated with a persistent reduction in blood flow. In 12 healthy subjects, blood flow in the left jaw was found not to be statistically different to that in the right jaw. PMID- 1873283 TI - Free jejunal transfer in oral reconstruction. AB - Free jejunal transfers have been used for intra-oral reconstruction after extensive oral carcinoma resection in Munster since 1983. Reconstruction has been carried out for tumours at different locations within the oral cavity and oro pharynx. The indications are presented for this procedure and a description is given of the surgical technique. The follow-up experience of 27 patients over a period of 6 years is discussed with particular reference to problems encountered. PMID- 1873284 TI - Bilateral accessory digastric muscles. AB - Anomalies of the anterior bellies of the digastric muscles are uncommon. The description of such anomalies do exist in the literature dating from the 19th Century, but recently radiologists have drawn attention to their existence to avoid confusion with abnormal lesions when scanning the floor of the mouth and the submental space. Bilateral accessory muscles crossing the midline are described. PMID- 1873285 TI - Transconjunctival approach to the infraorbital region: a cadaveric and clinical study. AB - The surgical anatomy of the transconjunctival approach to the infraorbital region was studied using fresh cadaver dissection, histological examination and in the clinical situation. The existence of a periorbital envelope which separates the orbital fat from the orbital septum, and a potential postseptal space was noted. Reference to these anatomical features could not be found in the literature. The postseptal space was used to gain access to the infraorbital rim and the orbital floor. Wire and plate osteosynthesis of the infraorbital rim and exploration and reconstruction of the orbital floor were performed without fat herniation into the operative field. Access was adequate for these procedures and lower lid malposition was not observed as a postoperative complication. PMID- 1873286 TI - A comparison of template bleeding time with mucosal petechiometry as a measure of the platelet function defect induced by aspirin. AB - The object of this study was to assess the value of mucosal petechiometry as a useful method of measuring the haemostatic defect induced by aspirin. The template bleeding time was done for comparison. The results indicated that mucosal petechiometry did not measure the haemostatic defect induced by aspirin and that aspirin-induced alterations in platelet function were not important in the development of petechiae in healthy subjects. PMID- 1873287 TI - British oral and maxillofacial surgeons' views on the aetiology and management of acute pericoronitis. AB - Acute pericoronitis is a common oral infection characterised by a predominance of anaerobic micro-organisms such as peptococci, peptostreptococci, bacteroides and fusobacteria, and also spirochaetes. Penicillins such as amoxycillin, and metronidazole are effective antimicrobials in the treatment of acute pericoronitis. This study presents the views of a group of British Oral and Maxillofacial Surgeons as to the causative microbial agents and the antimicrobial management of acute pericoronitis. PMID- 1873288 TI - Hazard warning. A case of postoperative pulmonary barotrauma. AB - A case is described in which extensive pulmonary barotrauma occurred due to the application of a face mask to an indwelling cuffed endotracheal tube. The design of the mask is such that a seal was made between the mask and the tube. The design of mask is widely used in theatre recovery areas and clinicians are alerted to this potential hazard. PMID- 1873289 TI - Primary hyperparathyroidism: evaluation of different treatments of jaw lesions based on case reports. AB - On the basis of three case reports, different treatment modalities of primary hyperparathyroidism of the jaws are presented. Surgical intervention made as the result of misdiagnosis in the first case caused an unnecessary bone defect and delayed bone regeneration for several months. Two other cases showed spontaneous regeneration of bone after parathyroidectomy. The second case disproved the earlier opinion that regeneration of the bone lesions could last for several years, and that the normal morphology could be restored. Complete resolution of the central giant-cell lesion was found 6 months after removal of the parathyroid adenoma. PMID- 1873290 TI - Gigantiform cementoma affecting a Caucasian family. AB - A Caucasian family is presented in which two out of three children showed lesions resembling gigantiform cementoma clinically, radiologically and histopathologically. Both affected children had swellings of the alveolar crest, caused by large, lobular, radio-opaque masses in all four quadrants of the jaws. Histologically, cementum-like masses were surrounded by inflamed fibrous connective tissue. There was evidence indicating that the late father had similar lesions which became malignant following radiation therapy. PMID- 1873291 TI - Facial pain and muscle atrophy secondary to an intracranial tumour. AB - Orofacial pain rarely arises from a distant site. It is unusual for orofacial pain to be associated with wasting of the facial musculature and diminished sensation. This case report describes a patient who presented with temporomandibular joint pain dysfunction syndrome which was initially successfully managed with splint therapy. She re-presented later with unilateral wasting of the muscles of mastication, facial pain and diminished sensation ipsilaterally. An intracranial meningioma was diagnosed following an extensive series of investigations. PMID- 1873292 TI - Neurilemmoma in the maxillary alveolar bone: report of a case. AB - Neurilemmoma located in the maxillary alveolar bone of a 64-year-old female is presented. A review of the literature yields only two previous cases of central neurilemmoma of the maxilla. PMID- 1873293 TI - Guide groove for pinning subcondylar fractures. AB - For pinning subcondylar fractures, a guide groove cut on the lateral surface of the mandibular ramus is a useful method of directing a Kirschner wire into the correct position. An extended groove correctly guides the pin in difficult cases. PMID- 1873294 TI - A modified anterior maxillary osteotomy: 15 years experience. AB - A modified technique of anterior maxillary osteotomy is described, based mainly on the Wassmund (buccal aspect) and the Wunderer (palatal aspect) methods. Experience of 148 cases operated on during 15 years is presented. PMID- 1873295 TI - Who's getting your fair share? Direct reimbursement--the deck is stacked. PMID- 1873296 TI - Free speech denied. 'Gag Rule' upheld as constitutional. PMID- 1873297 TI - Structural characterization of heme sites in spinach cytochrome b6f complexes: a resonance Raman study. AB - Resonance Raman spectra of cytochrome b6f complexes isolated from spinach chloroplasts have been obtained. Selective resonance enhancements and partial reductions of the complex by redox mediators were used to isolate and identify the contributions of heme b6 and heme f sites to the observed spectra. Corresponding spectra for turnip cytochrome f have also been obtained. Power dependent photoreduction was observed in cytochrome f of the complex as well as in the isolated cytochrome f during the course of the Raman experiments. PMID- 1873298 TI - Role of mitochondria in hepatic fructose metabolism. AB - During metabolism of fructose at concentrations exceeding 5 mM, isolated liver cells accumulate fructose 1-phosphate and lose ATP. At added bicarbonate concentrations below 10 mM in the incubation medium, the addition of atractyloside (or carboxyatractyloside) causes a significant net accumulation of 2-phosphoglycerate, resulting in an increase in the ratio 2-phosphoglycerate: 3 phosphoglycerate from below 1 to greater than 5. Digitonin fractionation revealed that virtually all this 2-phosphoglycerate is associated with the mitochondrial fraction, where it achieves a concentration estimated to be about 40 mM. The amount of 2-phosphoglycerate that accumulates is directly related to the initial concentration of fructose. With DL-glyceraldehyde in place of fructose, an even greater accumulation of 2-phosphoglycerate occurs, and this is also dependent upon both the presence of atractyloside and low bicarbonate. Formation of 2 phosphoglycerate is also observed when isolated mitochondria from rat liver are incubated together with glyceraldehyde and an energy source. The obligatory role of atractyloside for the accumulation of 2-phosphoglycerate within intact cells indicates the involvement of the mitochondrial adenylate translocator in this process, possibly as a carrier directly responsible for 2-phosphoglycerate egress from the mitochondrial matrix. If this is so, competition between 2 phosphoglycerate and ATP for egress from the matrix would be predicted to further exaggerate the fructose-induced depletion of cytosolic ATP. PMID- 1873299 TI - Stark effect spectroscopy of carotenoids in photosynthetic antenna and reaction center complexes. AB - The effects of electric fields on the absorption spectra of the carotenoids spheroidene and spheroidenone in photosynthetic antenna and reaction center complexes (wild-type and several mutants) from purple non-sulfur bacteria are compared with those for the isolated pigments in organic glasses. In general, the field effects are substantially larger for the carotenoid in the protein complexes than for the extracted pigments and larger for spheroidenone than spheroidene. Furthermore, the electrochromic effects for carotenoids in all complexes are much larger than those for the Qx transitions of the bacteriochlorophyll and bacteriopheophytin pigments which absorb in the 450-700 nm spectral region. The underlying mechanism responsible for the Stark effect spectra in the complexes is found to be dominated by a change in permanent dipole moment of the carotenoid upon excitation. The magnitude of this dipole moment change is found to be considerably larger in the B800-850 complex compared to the reaction center for spheroidene; it is approximately equivalent in the two complexes for spheroidenone. These results are discussed in terms of the effects of differences in the carotenoid functional groups, isomers and perturbations on the electronic structure from interactions with the organized environment in the proteins. these data provide a quantitative basis for the analysis of carotenoid bandshifts which are used to measure transmembrane potential, and they highlight some of the pitfalls in making such measurements on complex membranes containing multiple populations of carotenoids. The results for spheroidenone should be useful for studies of mutant proteins, since mutant strains are often grown semi aerobically to minimize reversion. PMID- 1873300 TI - Extracellular generation of active oxygen species catalyzed by exogenous menadione in yeast cell suspension. AB - Luminol chemiluminescence was observed by addition of menadione to yeast cell suspension and was amplified 1000-fold by further addition of Fe-complex. Catalase, superoxide dismutase and ceruloplasmin had inhibitory effects on luminol chemiluminescence, indicating the extracellular generation of active oxygens (H2O2 and O2-) and reduction of Fe-complex. The generation of H2O2 and reduction of Fe-complex were mainly dependent on the activity of NADH: menadione oxidoreductase in the plasma membrane and cytosol fractions. Both luminol chemiluminescence and H2O2 production were sensitive to the inhibitory effects of proton conductor, ionophorous antibiotics and ATPase inhibitor rather than the inhibitors of the mitochondria electron transport system. The incubation of glucose with yeast cells caused a parallel increase in luminol chemiluminescence, H2O2 production and intracellular NADH concentration. These facts suggest that menadione-catalyzed H2O2 production and chemiluminescence are used as the indicators of cell activity to keep the NADH concentration and NADH: menadione oxidoreductase activity which may be sensitive to the change in pH and ion concentrations. PMID- 1873301 TI - Spectrophotometric determination of some MAO inhibitors using 7,7,8,8 tetracyanoquinodimethane and iodine monochloride. AB - Two simple and sensitive spectrophotometric methods are described for the assay of three MAO inhibitors: isocarboxazid, tranylcypromine sulphate and iproniazid phosphate. The first method is based on the formation of a highly coloured stable radical anion between the drug as an n-donor and 7,7,8,8-tetracyanoquinodimethane (TCNQ) as a pi-electron acceptor. Beer's law is obeyed in the concentration range 0.2-3, 0.2-4 and 0.5-4 micrograms ml-1 for isocarboxazid, tranylcypromine sulphate and iproniazid phosphate, respectively. The second method involves the use of iodine monochloride (ICl) as an sigma-acceptor. It was found that ICl reacts quantitatively only with isocarboxazid and tranylcypromine sulphate; with iproniazid phosphate results were very poor. Beer's law is obeyed in the concentration range 2-20 micrograms ml-1 for both drugs. The optimum experimental parameters for colour production in each case were determined. The percentage recoveries obtained were in accordance with those obtained by the official methods. The proposed methods are characterized by high sensitivity. PMID- 1873302 TI - Simultaneous determination of imipramine and amitryptiline by derivative spectrophotometry. AB - Three methods are proposed for the simultaneous determination of imipramine and amitryptiline by derivative spectrophotometry, one of them using both first- and second-derivative spectra, and the others using the first- and second-derivative spectra, respectively, obtained from a "diode array" spectrophotometer. The methods allow the determination of 0.62-10.14 micrograms ml-1 of imipramine, and 0.63-10.04 micrograms ml-1 of amitryptiline, and have been applied to their determination in blood serum. PMID- 1873303 TI - Simultaneous determination of sulphathiazole and sulphanilamide in pharmaceuticals by derivative spectrophotometry. AB - Third-order and fourth-order derivative spectra have been used for determining sulphathiazole, sulphanilamide and their binary mixtures. The method is suitable for 1-22 micrograms ml-1 of sulphathiazole and for 0.5-14 micrograms ml-1 of sulphanilamide and can be applied for determining the sulphonamides in pharmaceuticals. PMID- 1873304 TI - Evaluation of solid-phase extraction of basic drugs from human milk. AB - This article evaluates the use of commercially available cyanopropyl and octadecyl sorbents for the extraction of basic drugs from breast milk. Twenty drugs were selected from different pharmacological groups (beta-blocking agents, antidepressants, anxiolytic sedatives and neuroleptics, antihistamines, alkaloids and an anthelmintic) and subjected to a general solid-phase extraction (SPE) procedure described earlier for plasma samples. This SPE method was developed on a cyanopropyl cartridge and consisted of a conditioning step with methanol and water, the adsorption of the deproteinized matrix, washing with water and/or methanol, and finally the elution of the basic compounds with 0.1% propylamine in methanol. The extracts were further analysed by reversed-phase liquid chromatography (RP-LC). The application of SPE to human milk samples utilized cyanopropyl and octadecyl cartridges. The latter can be applied more generally because it better retains the basic compounds. For 14 out of 17 drugs extracted from breast milk, recoveries of greater than 70% were obtained. Standard deviations were, with the exception of three drugs, in the same range as those observed for plasma samples, i.e. 2-8%. The development of a strategy for SPE of drugs from human milk was difficult. For a number of drugs, in particular those present in human milk at low concentrations and/or detected in a non-selective way, matrix compounds interfered with the subsequent LC analysis. Therefore, SPE on CN or C18-sorbent for the analysis of basic compounds in breast milk was found to be useful as one of the steps in an extraction procedure, but not as a single technique. A major drawback of SPE is the batch-to-batch variation of the sorbents. PMID- 1873305 TI - Measurement of the class III antidysrhythmic drug, UK-68,798, in plasma by radioimmunoassay. AB - A sensitive radioimmunoassay (RIA) for the specific determination of 1-(4 methanesulphonamidophenoxy)-2-[N-(4-methanesulphonamido -phenethyl)-N- methylamino]ethane (UK-68,798), a novel class III antidysrhythmic agent, in human plasma is described. Specific antisera were raised in sheep using desmesyl-UK 68,798-succinate-ovalbumin conjugate as the antigenic hapten carrier protein. The antisera produced exhibited high specificity for UK-68,798 compared with known metabolites from animals, other antidysrhythmic agents and co-administered drugs. Good correlation was found in a comparison of the RIA method with a high performance liquid chromatography (HPLC) method (r = 0.997) and a 10-fold lower limit of determination was observed for the RIA method compared with the HPLC method (0.05 and 0.5 ng ml-1, respectively). The RIA method was applied to the analysis of UK-68,798 in plasma obtained from human volunteers receiving the compound. PMID- 1873306 TI - Chromatographic and spectroscopic characterization of sulphur-bound dimetridazole and ranidazole derivatives. AB - The 5-nitroimidazoles, dimetridazole and ronidazole, two important veterinary drugs, were reacted under reductive conditions with the sulfhydryl-containing substrates cysteine and glutathione to yield 5-amino-4-S-substituted imidazoles. After purification by reversed-phase liquid chromatography (RP-LC), the four adducts were characterized by RP-LC with photodiode array detection using conditions where their parent drugs were not eluted from the column. Structural identification was conducted by spectroscopic techniques, mainly 1-dimensional and 2-dimensional NMR. While the dimetridazole adducts were found to be monosubstituted at the C-4 position, the two ronidazole products contained two units of the sulfhydryl substrate, located at the C-4 and C-6 positions. PMID- 1873307 TI - Continuous intravenous monitoring of levodopa and 3-O-methyldopa by microdialysis and high-performance liquid chromatography with electrochemical detection. AB - Microdialysis, in association with ion-pair reversed-phase high-performance liquid chromatography with electrochemical detection, was applied in vitro for the determination and quantification of levodopa and 3-O-methyldopa in blank spiked plasma and blood. The method presented gave accurate results; the calibration graphs for plasma were linear over the range of the expected values for both compounds. When using a dialysis probe with a membrane length of 1.6 cm at a 5 microliters min-1 perfusion speed, the recovery rate in plasma for levodopa was 30.1% and 68.5% for 3-O-methyldopa. However, less reproducible results were obtained for plasma levodopa levels in the range of 0.5 microliter ml-1 and lower. The microdialysis technique was subsequently successfully applied for the continuous intravenous monitoring of levodopa and 3-O-methyldopa in a levodopa-treated dogs. PMID- 1873308 TI - Simultaneous determination of levodopa, its main metabolites and carbidopa in plasma by liquid chromatography. AB - An ion-pair reversed-phase liquid chromatographic method for the simultaneous determination of levodopa, 3-O-methyldopa, 3,4-dihydroxyphenylacetic acid, homovanillic acid and carbidopa in plasma designed for clinical trials performed to study the effect of peripheral catechol-O-methyltransferase inhibitors on the metabolism of levodopa is described. The high sample throughput of over 50 samples per day of the method makes it ideal for the assay of the large number of samples encountered in clinical trials. After protein precipitation with perchloric acid the analytes are completely separated within 15 min and determined down to a plasma concentration of 20 ng ml-1 using amperometric detection at 800 mV relative to an Ag/AgCl reference electrode. For all analytes the within-day precision defined as a relative standard deviation (n = 8) is lower than 7 and 3% at plasma concentrations of 20 and 40 ng ml-1, respectively. As the method is specific and highly reproducible, the most important factor affecting accuracy is the stability of the analytes during storage and analysis. PMID- 1873309 TI - Reversed-phase high-performance liquid chromatography method for the determination of bemegride in serum and brain tissue: pharmacokinetics and brain distribution of an intraperitoneal subconvulsive dose in rats. AB - A simple and rapid HPLC method has been developed for the quantification of bemegride in serum and brain tissue, using p-methylphenobarbital as an internal standard. Serum and brain tissue homogenate samples were extracted with ethyl acetate and the evaporated and redissolved extracts injected into a reversed phase column. The compounds were eluted with an acetonitrile-phosphate buffer mixture and monitored at 200 nm. A linear response was obtained in the range 1-40 micrograms ml-1 for serum and 1-40 micrograms g-1 for brain tissue. Within-day and between-day precisions were less than 5% and the analytical recovery greater than 76.4%. This method has been used to investigate the kinetic profiles of the drug in serum and discrete areas of rat brain after intraperitoneal administration of a subconvulsive dose of bemegride (10 mg kg-1). Peak concentrations occurred in the brain and serum at the same time (30 min), followed by a biphasic decay. The results also indicated the accumulation of the drug in the brain, with no significant differences (p greater than 0.05) in the impregnation of the different brain areas investigated. PMID- 1873310 TI - Micro-method for the determination of piperacillin in plasma by high-performance liquid chromatography. AB - A simple and sensitive high-performance liquid chromatographic method for the determination of piperacillin in plasma is described. A C8 reversed-phase column was used with a mobile phase consisting of methanol-water-triethylamine (550:450:4, v/v/v) adjusted to pH = 3 with orthophosphoric acid and UV detection at 270 nm. Cephalothin was used as internal standard. The method involves a plasma protein precipitation with acetonitrile followed by extraction of endogenous compound with chloroform and injection of the upper aqueous phase into the chromatograph. Within-day and between-day assays give relative standard deviations less than or equal to 5.7%. The detection limit is 0.2 microgram ml-1. Stability studies show that piperacillin degradation starts at -4 degrees C. Therefore, samples have to be processed promptly and stored at -20 degrees C. The method described is convenient for clinical monitoring and for pharmacokinetic studies. PMID- 1873311 TI - Spectrophotometric determination of amoxycillin and dicloxacillin in binary mixtures and in capsules. PMID- 1873312 TI - The use of direct determination of chromium in human urine by electrothermal atomic absorption spectrometry in diabetic patients. PMID- 1873313 TI - Determination of homatropine hydrobromide in eye drops by second-order derivative spectroscopy. PMID- 1873314 TI - Coulometric determination of sulphisomidine, sulphamethoxydiazine and sulphamoxole. PMID- 1873315 TI - Investigation and spectrophotometric determination of the allprenolol hydrochloride-iron (III) complex in bulk drug and in dosage form. PMID- 1873316 TI - Determination of famotidine in human plasma and urine by high-performance liquid chromatography. PMID- 1873317 TI - Spectrophotometric determination of diclofenac sodium in tablets. AB - Simple spectrophotometric methods are described for the determination of diclofenac. In the first method diclofenac reduces iron(III) to iron(II) when heated in aqueous solution. The ferrous ions produced react with 2,2'-bipyridine to form a complex having a maximum absorbance at 520 nm. The reaction obeys Beer's Law for concentrations of 10-80 micrograms ml-1. This method can be applied to the determination of diclofenac in tablets. In the second method, diclofenac is treated with Methylene Blue in the presence of phosphate buffer (pH 6.8) and the complex is extracted with chloroform. The complex has a maximum absorbance at 640 nm and the graph of absorbance against concentration is linear in the range 5-40 micrograms ml-1. This method can be applied to the determination of diclofenac in tablets that also contain paracetamol. PMID- 1873318 TI - Electrochemical analysis of cephalosporin antibiotics. AB - A review is presented on electroanalysis studies and methods for the determination of cephalosporin antibiotics in either simple solutions or biological fluids. Some general data about the electroactivity of cephalosporins are given and the analytical utilization of those data together with the corresponding analytical parameters, compiled from different literature sources. PMID- 1873319 TI - A liquid-chromatographic method for the determination of tobramycin. AB - A rapid and sensitive liquid-chromatographic method was developed to quantify the release of tobramycin from polymeric drug delivery systems in vitro. Pre-column derivatization of tobramycin and kanamycin B sulphate (internal standard) was carried out with 2,4,6-trinitrobenzenesulphonic acid. The sample volume required was only 50 microliters. The chromatographic separation was achieved on an octyl reversed-phase column with UV detection at 340 nm. This isocratic method was performed at ambient temperature and required only 8 min of chromatography time. The standard curves were linear over the concentration range 0.50-50.0 mg l-1. Inter-day and intra-day relative standard deviations ranged from 3.6 to 9.3% and from 1.6 to 6.8%, respectively. The assay method was used to determine the tobramycin content in different pharmaceutical formulations and to study the stability of the drug both in the solid-state and in solution. PMID- 1873320 TI - Determination of pentoxifylline in serum by high-performance thin-layer chromatography. AB - An analytical method to study the bioavailability of newly developed pentoxifylline sustained-release tablets has been developed and assessed in experiments on dogs. For the isolation of pentoxifylline and its metabolites from serum solid-liquid extraction was applied by involving the internal standard probe. HPTLC plates with a preconcentration zone were used for separation of the analysed substances, using chloroform-methanol (95:5, v/v). Quantification was by densitometric detection. The detector response was linear in the concentration range investigated for pentoxifylline: 0.02-1.5 micrograms ml-1 of serum. PMID- 1873321 TI - Sensitive liquid chromatography assay for the determination of amikacin in human plasma. AB - A selective LC method with on-line post-column derivatization is described for the determination of amikacin in biological fluids. Chromatography was performed on a reversed-phase column, using pentane sulphonic acid as an ion-pairing reagent. For the analysis of biological fluids, amikacin and the internal standard tobramycin were extracted using an ion exchanger (Sephadex). Following complete removal of plasma proteins, the aminoglycosides were eluted with alkaline sodium sulphate solution and injected into the chromatograph. After chromatographic separation the eluent was mixed with the derivatization reagent (o-phthalaldehyde and mercaptoethanol in borate buffer pH 10.4) in a reaction coil at 50 degrees C. Detection was performed by fluorescence (excitation: 340 nm, emission: 418 nm). The overall run time was 8 min, at a flow rate of 1.2 ml min-1. The limit of quantification was 25 ng ml-1 for amikacin in plasma. PMID- 1873322 TI - Evaluation of toxicity of catfish skin toxin using diffuse reflectance methods. PMID- 1873323 TI - The selection of buffer salts for the high-performance liquid chromatography of basic compounds. PMID- 1873324 TI - [Psycho-emotional distress and gastroesophageal reflux syndrome]. AB - 61 patients with symptoms suggestive for gastro-esophageal reflux (GER) disease, with or without endoscopic evidence of esophagitis, were studied in order to recognize any neurotic traits connected to GERD and its esophageal motility disorders. The results were compared with those from a group of patients without digestive diseases as well as those from a control group of the same age and status. Psychological assessment was made by using the Middlesex Hospital Questionnaire and esophageal motility pattern was analyzed with a low-compliance manometric system. Patients with gastro-esophageal reflux (GER), irrespectively or not from esophagitis, showed, after such a psychological assessment, neurotic traits more pronounced than control subjects and patients without digestive disease. In GER patients, it was observed a close relationship between some psychological traits and a few esophageal manometric variable. In the two groups of GER patients, with and without esophagitis, it was not found any significant difference in scores referring to the evaluated psychological traits apart from symptoms somatization, prevailing in GER patients without esophagitis. These results support the pathogenetic role of psychological distresses in the genesis of GER, even if other factors may be necessary to the development of organic inflammatory lesions such as esophagitis. PMID- 1873325 TI - [Limitations of the traditional manometric test and advantages of computerized manometry in the study of esophageal motility]. AB - The analysis of esophageal motility tracings is laborious, time consuming and subject to reader variability. The motility traces of five patients were analyzed separately by five experienced readers, in order to assess the inter and intra observer variability. Later on, the manual analysis of the motility traces of five healthy volunteers and four patients was compared to the automatic analysis performed by a computerized system. The inter- and intra-observer variability (expressed as coefficient of variation) was high in the manual analysis, especially for the abdominal length of the lower sphincter and the duration of the esophageal body contractions (coefficient of variation ranging from 18 to 43%). On the contrary, automatic readings proved almost identical to the means obtained by manual analysis (Pearson factor 0.988 for amplitude and 0.89 for the duration of contractions). Moreover, the computerized automatic analysis gave a significant time gain in respect to manual readings and eliminated the inter and intra-observer variability. PMID- 1873326 TI - [Indications and limitations of 24-hour gastric pH-metry. Personal experience]. AB - After a brief introduction regarding 24-hours gastric pH monitoring and a description of the instruments used, indications and the analysis of findings, the authors report their personal experience based on the study of 4 groups of subjects (healthy, hyersecretory, hyposecretory, dyspeptic). The analysis of pH metries observed in these subjects show that 24-hour monitoring of gastric pH is a reliable method for assessing hypersecretion or hyposecretion of gastric acidity, whereas it is only of relative importance in essential dyspepsia. The authors therefore indicate the parameters to be taken into account in the evaluation of pH-metry findings in hypersecretory patients: 1) the percentage time of which pH is less than 1 (mean value 46.20 +/- 28.2);2) the pH pattern assessed according to the circadian rhythm which shows a prandial and post prandial tamponade which is lower than normal with a rapid return of pH to extremely low values; 3) the visual graphic assessment for an overall judgement of pH patterns; and in hyposecretory patients: 1) the percentage time for which pH is higher than 7 (mean value 47.92 +/- 52.08); 2) enhanced pH levels ranging between 0 and 4 (mean percentage 9.67 divided by 27.08); 3) pH values at times 0, 1, 2, 3 which confirm hyposecretion in the meal causes a marked and long-lasting tamponade with pH levels above 6-7. Even in these cases the visual graphic assessment is important for an overall definition of 24-hour ph patterns. PMID- 1873327 TI - [Ursodeoxycholic acid for the treatment of chronic diseases of the liver. Short term results]. AB - The tolerance and the effect of ursodehoxycholic acid (UDCA) on the level of transaminases and gammaglutamyl-transpeptidase (GGT) has been estimated, over the short term, in 27 patients affected by compensated liver cirrhosis in comparison to 24 patients, representing the control group. The results were good with regard to GGT values, as a meaningful reduction was observed during the first month of therapy which then improved in the next five months. There was also a significant reduction in transaminase levels at the end of the second month of therapy, which was maintained until treatment was stopped; mean values however were not within the normal range. These results, together with tolerance of the drug confirm a role of UDCA in the treatment of chronic liver diseases in an advanced stage. PMID- 1873328 TI - [Genetic epidemiology of cholelithiasis. A case-control study of a population]. AB - Aim of this study is to evaluate the familial risk of cholelithiasis in non hospitalized subjects with and without gallstones. A population sample of 2.472 subjects was examined by echography for gallstones; 220 subjects (92 males and 128 females) had gallstones or had already been cholecystectomized for gallstones. These cases and an equal number of controls were interrogated about the diagnosis of gallstones in their family using a standardized questionnaire. The comparison of the frequency of symptomatic gallstones and cholecystectomies for gallstones in the relatives of cases and controls showed an increase of the relative risk of gallstones in sons of parents with cholelithiasis (OR 2.9, CI 95% 1.2-8.0) and in siblings of subjects with cholelithiasis (if sister with gallstones: OR 2.4, CI 95% 1.05-5.6; if brother with gallstones: OR 2.9, CI 95% 0.6-14.6). The stratification for sex of cases and controls, however, pointed out that the risk increased only in daughters and sisters of subjects with gallstones. There was no statistically significant difference of frequency of gallstones between spouses of cases and controls (chi square, p greater than 0.05). The results of this study confirm that there is a familial risk of gallstones, even if it is evident only in the female relatives of subjects with gallstones, and suggest that probably the main cause of this risk is genetic and not environmental. PMID- 1873329 TI - [Role of surgery in the multidisciplinary treatment of lithiasis of the common bile duct]. AB - The efficacy of surgery was evaluated in 32 patients with common bile duct stones. Twenty-two patients have not undergone a previous cholecystectomy. In 13 cases an endoscopic approach was attempted before surgery. In 13 patients biliary intestinal anastomoses were performed for large stones or bile duct strictures. In 19 cases common bile exploration with biliary drainage insertion was performed for uncomplicated biliary stones. We had no mortality and morbidity was 9%. We conclude that surgery is the treatment of choice in patients with gallbladder in situ or in cases of endoscopic failure. Endoscopic sphincterectomy may be preferred in poor-risk patients. PMID- 1873330 TI - [Physiopathology of malabsorption syndrome]. PMID- 1873332 TI - Home care nursing. At the crossroads. PMID- 1873331 TI - [Primary sclerosing cholangitis associated with colonic Crohn disease and marked eosinophilia. Description of a case]. AB - We report a case of primary sclerosing cholangitis associated with Crohn disease of the large intestine and marked eosinophilia in a 64 year old woman. Clinical features, histologic findings at biopsy of the intestine and liver and the endoscopic retrograde cholangiopancreatography are described. The case report is discussed, particularly as regards treatment with biliary salts and aminosalicilic acid. PMID- 1873333 TI - Give yourself the chance of a lifetime. PMID- 1873334 TI - Andrea Henning, B.C.'s new provincial nurse advisor. Interview by Bruce Wells. PMID- 1873335 TI - Home, but not alone. PMID- 1873336 TI - Nursing research: the practice connection. PMID- 1873337 TI - Therapeutic abortion. PMID- 1873338 TI - The way it was. Interview by Laura Brown. PMID- 1873339 TI - Registered Nurses Association of British Columbia. Position statement. Marketing of breast-milk substitutes. PMID- 1873340 TI - [Annexins--a new family of Ca(2+)-binding proteins]. AB - Annexins, the Ca(2+)- and phospholipid-binding proteins, are able to induce Ca(2+)-dependent aggregation of biomembranes. All the representatives of this family contain four or eight tandem repeats, 60-80 amino acids each. All these repeats include a highly conservative 17-member amino acid consensus sequence (an endonexin fold). The central domain comprises all these repeats and contains, in addition, the site(s) with a binding affinity for Ca2+ and phospholipids. Annexins are devoid of the classical "EF-hand" Ca(2+)-binding domain and can therefore be assigned to a new family of Ca(2+)-binding proteins. PMID- 1873341 TI - [New 26 kDa protein specific for photoreceptor cells, capable of binding with immobilized delipidized rhodopsin]. AB - A protein p26 with molecular weight 26 kDa capable of binding to delipidated rhodopsin immobilized on Concanavalin A-Sepharose was found in photoreceptor cells of bovine retina. Mono specific antibodies against this protein were used to demonstrate this protein to be located in a layer of photoreceptor cells, both in their inner and outer segments. On the basis of its antigenic properties p26 is different from any other known photoreceptor cells-specific proteins. PMID- 1873342 TI - [Role of active forms of oxygen in inducing luminol-dependent chemiluminescence in macrophages]. AB - The luminol-dependent chemiluminescence of mouse peritoneal macrophages during phagocytosis of opsonized zymosan was studied by using specific active oxygen scavengers and metabolic inhibitors. Extracellular hydrogen peroxide and superoxide anion were shown to contribute immensely to the induction of the chemiluminescence. The role of the hydroxyl radical was rather insignificant, whereas singlet oxygen was not involved in this process. The interaction between luminol and peroxide was shown to be peroxidase-dependent. An inhibitory analysis revealed that the interaction between luminol, peroxide and superoxide anion obeyed a hybrid enzyme-free radical mechanism. PMID- 1873343 TI - [Photoconversion of hemoglobin forms in buffer solutions under the effect of ultraviolet and visible radiation]. AB - Using spectrophotometric methods, the photochemical behaviour of hemoglobin in buffer solutions irradiated at 254-578 nm was studied. It was found that the hemoglobin photochemical activity is manifested in a cascade of photoreactions involving at least four protein forms and soluble oxygen. Hemoglobin photoconversions were observed both upon light absorptions by the globin and the heme. The efficiency of photoreactions decreased with an increase in the wavelength of the irradiating light. The values of quantum yields of the above photoreactions were determined. PMID- 1873344 TI - [Effect of sphingomyelin and its enzymatic hydrolysis products on heterologous methylation of calf thymus DNA by cytosine-DNA-methyltransferase EcoRII]. AB - It was found that sphingomyelin and its enzymatic hydrolysis products, choline and sphingosine, influence the degree of DNA methylation in the reaction of heterologous methylation by methylase EcoRII in vitro. Sphingomyelin was found to be able to was activate (by 20%), sphingosine and choline inhibit methylation. Phosphatidylcholine had no effect on DNA methylation in an in vitro system. The role of lipids in the regulation of gene expression during enzymatic modification (methylation) of DNA is discussed. PMID- 1873345 TI - [Phospholipase A2 activity in human platelets. Isolation and purification of the enzyme]. AB - The activity of phospholipase A2 in blood platelets of healthy donors and IHD patients was examined. The enzyme activity was found to be increased 3-fold in platelets possessing a high level of functional activity (IHD) and by one order of magnitude in patients with myocardial infarction as compared with healthy donors. An enzyme preparation possessing a phospholipase activity was isolated from platelets by using salt extraction (KCl) and sonication. Purification of the enzyme by affinity chromatography resulted in two protein peaks both having a phospholipase A2 activity, the purification and molecular masses of these fractions being 768- and 2200-fold, and 13.5 and 15 kDa, respectively. It was supposed that these proteins are substrate-specific forms of phospholipase A2. PMID- 1873346 TI - [Dependence of human erythrocyte methemoglobin reductase on temperature]. AB - The effect of temperature on the activities of cytoplasmic and membrane-bound fractions of NADH-cytochrome beta 5 reductase on the total activity of methemoglobin reductase in intact human erythrocytes was studied within the temperature range of 20-50 degrees C. The above three activities showed a break in the Arrhenius plots at 42 degrees C which was attributed to irreversible inactivation of the enzymes. Thermal inactivation of methemoglobin reductase in erythrocytes was found to increase the methemoglobin content concomitantly with a decrease in the osmotic stability and activation of spontaneous cell hemolysis. PMID- 1873347 TI - [Regulation of sphingomyelinase and phospholipase C activity in liver cell membranes of rats of different ages]. AB - The changes in the functional activities of sphingomyelinase and phospholipase C from rat liver cell plasma membranes were studied in postnatal ontogenesis in the presence of thyroxin and mercasolyl. It was found that endogenous phospholipases of plasma membranes control of phospholipid content in rat liver cells. The sphingomyelinase activity is under control of thyroid hormones, whereas that of phospholipase C which is phosphatidyl choline-specific, is unaffected by them. The data obtained testify to the possible involvement of diacylglycerols formed via enzymatic hydrolysis of phosphatidylcholine, in the regulation of the sphingomyelinase activity. PMID- 1873348 TI - [The role of vitamin E in the biosynthesis of ubiquinone (Q) and ubichromenol (QC) in rat liver]. AB - Some peculiarities of ubiquinone (Q) biosynthesis in the livers of vitamin E deficient rats induced in vitro by alpha-tocopherol and S-adenosylmethionine (SAM) were investigated. When [C3H3]SAM was used as a precursor, alpha-tocopherol added to the sample induced a marked elevation of the content of Q concomitantly with a drastic increase (2.82-fold) of specific radioactivity of Q in the liver as compared to control. Under identical conditions with 2-14C sodium acetate as precursor, exogenous alpha-tocopherol increased the content (by 31.4%) and specific radioactivity (by 65.2%) of Q in experimental samples, whereas the corresponding parameters of ubichromenol (QC) were essentially unchanged. SAM added to the incubation medium caused a marked increase in the content and specific radioactivity of both Q and QC as compared to control. Similar, and even more conspicuous changes were observed after combined administration of alpha tocopherol and SAM. The role of vitamin E in the activation of methylation reactions at terminal steps of Q and QC biosynthesis in rat liver is discussed. PMID- 1873349 TI - [Interaction of [3H]AMP with liver cells and their plasma membranes]. AB - Specific binding of [3H]AMP to rat hepatocytes and their plasma membranes was studied. It was shown that the time course of this binding reached a maximum within the first 15 seconds. An equilibrium binding study revealed the presence of a single class of binding sites with Kd of 20 microM both in hepatocytes and in plasma membranes. The [3H]AMP binding sites were inactivated by treatment with trypsin as well as by heating. 5'-Phosphorylated derivatives of adenosine (ATP, ADP) effectively competed with [3H]AMP for the binding sites, while adenosine, beta-glycerophosphate and 3'-AMP were inactive. The binding of [3H]AMP increased by 400% in the presence of concanavalin A, a specific inhibitor of plasma membrane 5'-nucleotidase. It was concluded that the catalytic center of 5' nucleotidase is a receptor for adenine nucleotides. PMID- 1873350 TI - [Autophosphorylation of EGF receptors in the A431 cell line with an increased intracellular concentration of Ca(2+) ions]. AB - The increase in the intracellular concentration of Ca2+ in A431 cells induced by the calcium ionophore A23187 leads to phosphorylation of epidermal growth factor (EGF) receptors at serine and/or threonine residues. This process is accompanied by the decrease in the level of EGF receptor autophosphorylation at tyrosine residues. Preincubation of cells in a A23187-containing medium in the presence of phorbol-12-myristoyl-13-acetate leads to a further decrease of the phosphotyrosine content in EGF receptors. At increased intracellular concentrations of Ca2+ preincubation of A431 cells with the protein kinase C inhibitor H-7 has no effect on the degree of EGF receptor autophosphorylation. Down-regulation of cellular protein kinase C does not change the A23187-induced effect either. The data obtained suggest that the decreased autophosphorylation of EGF receptors induced by Ca2+ is not due to the activation of cellular protein kinase C. PMID- 1873351 TI - Rapid screening for cell surface binding monoclonal antibodies. AB - A procedure is described which allows for rapid detection of cell surface binding or cytoskeleton binding monoclonal antibodies. At the same time this procedure ensures that selected antibodies will be useful in Western blot analysis. This procedure including the cytochemistry and Western blot analysis requires only 100 microliters of supernatant and can be done directly from the original 96 well plates into which the fusion was plated. One person can easily assay several hundred supernatants in one day for the ability to stain both cells and selected proteins in Western blot analysis. PMID- 1873352 TI - Use of silver enhancement technique for immunohistochemical detection of epidermal growth factor in rat submandibular gland. AB - Low temperature photochemical silver staining was used for immunohistochemical demonstration of epidermal growth factor (EGF) in the rat submandibular gland. EGF was shown to be clearly localized in granular convoluted tubule cells. Silver staining with an immunogold method showed excellent resolution of the antigen localization. PMID- 1873353 TI - Interleukin-2 and syngeneic bone marrow transplantation in a murine fibrosarcoma model. AB - Mice received interleukin-2 (IL-2) either before and after, or just after intravenous inoculation of syngeneic fibrosarcoma cells. Fewer pulmonary tumor colonies were observed in those animals treated with IL-2, and the best results were observed when IL-2 was administered prior to tumor inoculation. When mice were lethally irradiated and reconstituted with tumor-contaminated bone marrow, IL-2 treatment was also associated with fewer tumor lung colonies. IL-2 may prove to be a useful adjuvant therapy, particularly in the setting of autologous bone marrow transplantation when the infused marrow is contaminated with tumor cells. PMID- 1873354 TI - Activation of human dermal fibroblasts by fibroblast growth factors (FGFs) and/or interleukin-1 beta (IL-1 beta). AB - Human dermal fibroblast proliferation was dependent of growth factors such as interleukin-1 (IL-1) and fibroblast growth factors (FGFs). These mediators, which induce proliferation of the cells in culture, were able to synergize when added in combination. This synergistic effect seems to be restricted to the mitogenic activity since IL-1-induced PGE2 release and interferon-beta 1 (IFN-beta 1) production by fibroblasts was inhibited in the presence of FGFs, which by themselves were unable to stimulate the production of IFN-beta 1 and the release of arachidonate metabolites from the fibroblasts even at high concentration. PMID- 1873355 TI - The interrelation between TNF, IL-6, and PAF secretion induced by LPS in an in vivo and in vitro murine model. AB - The interrelation between TNF, IL-6, and PAF secretion in an in vivo and in vitro murine model was studied. Mice were injected with LPS, giving rise to considerable TNF and IL-6 serum levels. To determine the influence of TNF production on the IL-6 secretion, one group of mice was treated with an anti-TNF mAb before LPS administration. The LPS-induced IL-6 secretion was reduced to 48% in the anti-TNF-pretreated group. Parallel to the in vivo experiments, cultures of murine peritoneal macrophages were stimulated with LPS. IL-6 secretion was diminished for 25% in presence of anti-TNF mAb. Further, the role of PAF released in response to a challenge with LPS in the regulation of TNF and IL-6 production was investigated. TNF secretion was strongly reduced when cultures of peritoneal macrophages were stimulated with LPS in the presence of a PAF antagonist, whereas IL-6 secretion was not altered by the PAF antagonist. However, pretreatment of mice with a PAF antagonist did not influence serum TNF, nor serum IL-6 levels induced by LPS injection. These data show that TNF was an intermediate in the induction of IL-6 production in vivo and in vitro. PAF played a central role in the TNF release in the in vitro experiments. This could, however, not be established in vivo. LPS-induced PAF secretion was not involved in the regulation of IL-6 secretion. PMID- 1873356 TI - A simple nonisotopic in vitro bioassay for LT and TNF employing sodium fluoride treated L-929 target cells that detects picogram quantities of LT and TNF and is as sensitive as TNF assays done with ELISA methodology. AB - We have developed a highly sensitive in vitro bioassay for lymphotoxin (LT) and tumor necrosis factor (TNF). This system employs a monolayer of 20,000 L-929 target cells in each well of 96-well microplates that are incubated in dilutions of LT and TNF at 37 degrees C for 20-24 h, after which the viability of the L-929 target cells is assessed by spectrophotometric techniques. We find that incorporation of 2 mM NaF increases the sensitivity of L-929 cells to lysis by 10(3)-10(4) x for LT and 10(4)-10(5) x for TNF. This method allows the regular detection of less than 1-5 pg of bioactive protein. ELISA assays did not detect synthetic TNF and TNF fragments that were not biologically active in this assay. The L-929 bioassay requires no isotopes, is very reproducible, is as sensitive as ELISA techniques, and detects only biologically active LT and TNF. PMID- 1873357 TI - Interleukin-1 beta stimulates bone resorption and inhibits bone formation in vivo. AB - Interleukin-1 beta (IL-1 beta) and several other cytokines, including IL-1 alpha, tumor necrosis factor (TNF), and lymphotoxin, stimulate bone resorption and also inhibit bone formation in vitro. These effects are consistent with an uncoupling function for these mediators, although the effect of in vivo regulatory mechanism(s) that couple resorption and formation cannot be adequately evaluated in vitro. In the present studies, the effect of IL-1 beta on bone resorption and formation was determined in adult rats in vivo. Resorption was assessed by serum and urinary calcium levels, osteoclast number, and active resorption surface. Bone formation was determined by measurement of serum osteocalcin levels, and by quantitation of bone apposition rate using tetracycline labeling. A modest dose of IL-1 beta (1 microgram/kg) was found to stimulate transient increases in serum calcium, and a persistent elevation of urinary calcium excretion. IL-1 beta treatment also resulted in decreases in serum iron levels and in the albumin/globulin ratio, well-established in vivo effects of IL-1. SGOT, SGPT, BUN, creatinine, and total protein were unaffected, indicating that IL-1 beta treatment did not compromise kidney or liver function, and that animals were systemically healthy. This was further evidenced by normal weight gain in IL-1 beta-treated animals. Low doses (50 micrograms/kg) of synthetic human parathyroid hormone (PTH 1-34) also stimulated resorption, as shown by a sustained increase in serum calcium without increased urinary excretion. Both IL-1 beta and parathyroid hormone (PTH) stimulated similar increases in osteoclast number (N.Oc) and active resorption surface [Oc.S(%)].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873358 TI - The role of macrophages in experimental arthritis induced by Streptococcus agalactiae sonicate: actions of macrophage colony-stimulating factor (CSF-1) and other macrophage-modulating agents. AB - Intraperitoneal injection of Streptococcus agalactiae sonicated cells into Wistar rats causes a chronic relapsing polyarthritis resembling human rheumatoid arthritis. We report evidence favoring a role for macrophages in the pathology of this disease. S. agalactiae injected ip induced a high level of tumor necrosis factor release by peritoneal macrophages isolated subsequently, and had a similar effect when added to control peritoneal macrophages in culture. Ia antigen was induced on macrophages in both the peritoneum and affected joints following S. agalactiae injection. The role of macrophages in the disease process was studied by treating animals prior to S. agalactiae injection with varying concentrations of bacterial lipopolysaccharide (LPS), silica, and carrageenan, agents known to have a biphasic effect on macrophage function. They aggravated the pathology at low doses but prevented the disease at high doses. The most specific alteration of macrophage levels was achieved by injection of recombinant human macrophage colony-stimulating factor (CSF-1). Treatment with CSF-1 early in the disease lead to significant worsening of the pathology. Administration of CSF-1 after 2 weeks reactivated the disease and extended the chronic phase. These data in combination with previous findings are consistent with nonimmune, macrophage-mediated pathology for this model of arthritis. The results have implications for therapeutic application of CSF-1. PMID- 1873359 TI - Evaluation of measurement of human TNF in plasma by ELISA. AB - The performance of a sandwich-ELISA for TNF measurement in plasma and serum was studied. The ELISA was first statistically analyzed. Interassay coefficient of variance and the intraassay coefficient of variance for the concentration range between 0.5 and 5 ng/ml was less than 10%. The sensitivity of the sandwich-ELISA for TNF in culture medium was 10 pg/ml. The ELISA was shown to be specific for biologically active TNF, since a good correlation between the ELISA and the WEHI bioassay was observed when partially inactive, denatured TNF was measured. The effect of various anticoagulation systems on the reliability of human TNF measurement has been evaluated. The oxalate/NaF and EDTA systems were both appropriate, as appeared from the observed blockade of the production of TNF in the tube, either in the cell-glycolysis-blocked or in the calcium-depleted situation, respectively. An eventual decrease in the recovery of rTNF after collection of blood was prevented in the oxalate/NaF tubes. Recovery of TNF in the ELISA was diminished in the presence of plasma or serum. Techniques to enhance the efficiency of the measurement of TNF in plasma by ELISA were compared. The data indicate that in the presence of 1.1 M NaCl, the TNF masking effect of normal plasma was largely abrogated. The presence and role of inhibiting plasma components in plasma of healthy and diseased individuals are discussed. PMID- 1873360 TI - Therapy of recurrent high-grade gliomas with surgery, autologous mitogen activated IL-2-stimulated (MAK) killer lymphocytes, and rIL-2: II. Correlation of survival with MAK cell tumor necrosis factor production in vitro. AB - Seven patients with recurrent high-grade glioma were treated in a Phase I/II trial with surgical debulking, after which mitogen-activated IL-2-stimulated killer (MAK) lymphocytes and 10(5) units rIL-2 were implanted in the surgical defect. The therapy was well tolerated, and the mean survival of this group of patients was 29 weeks. Tumor necrosis factor (TNF) production by MAK lymphocytes stimulated with IL-2 in vitro was measured. A significant (r = .78, p = .04) correlation between survival of patients after therapy and the ability of the MAK lymphocytes to produce TNF in vitro was noted. A significant negative correlation (r = -.82, p = .02) was found when comparing TNF production and increasing tumor size measured on MRI. No correlation was found between TNF production in vitro and MAK lymphocytes lytic activity on K562 and U373 target cells. No correlation was found between survival and MAK cell lytic activity measured on K562 and U373 target cells. We conclude that TNF production in vitro and cytotoxic activity measured in vitro are measures of different antitumor activity in vivo and in vitro. TNF production during IL-2-stimulated proliferation may be an important in vitro assay in terms of predicting length of survival of recurrent high-grade gliomas. PMID- 1873361 TI - Effect of excess dietary fat during the third trimester of pregnancy on maternal, placental, and fetal metabolism in the pig. AB - The effect of excessive intake of dietary fat during late gestation on maternal, placental, and fetal metabolism was studied. Twelve pregnant gilts were fed ad libitum diets containing 4 (control) or 55% (added fat) calories as fat, beginning on day 70 of gestation. On day 110, glucose and palmitate oxidation, and incorporation into fatty acids by maternal adipose tissue, maternal and fetal placenta, and fetal liver and adipose tissue were determined. Caloric efficiency and adipose tissue glucose utilization were reduced in the added fat gilts, while placenta metabolism at high media palmitate concentrations was increased. Fetal development and metabolism were for the most part unaffected by maternal diet; thus, the fetus appears to be protected from dietary excess through adaptations of both maternal and placental metabolism. PMID- 1873362 TI - Body composition and cold resistance of the neonatal pig from European (Large White) and Chinese (Meishan) breeds. AB - Body composition, plasma parameters and cold resistance were compared in neonatal pigs from Chinese (Meishan, Ms) and European (Large White, Lw) breeds. Newborn Ms pigs weighed less but had a higher (p less than 0.05) percentage of body dry matter and protein than the Lw pigs, whereas both breeds had similar levels of body fat and liver and muscle glycogen. Plasma concentrations of fructose and alpha-fetoprotein were lower (p less than 0.05) in the newborn Ms pigs. Cold resistance test performed in a 6-7 degrees C environment on the same piglets when aged 2 and 24 h, showed that in both breeds, cold resistance was closely dependent upon body weight and significantly improved (p less than 0.01) with age. Despite their 16% lower body weight, Ms piglets were, at both ages studied, as resistant to cold as the Lw ones. Breed had no effect on pretest concentration of plasma glucose and noradrenaline, but pretest concentrations of plasma free fatty acids (FFA) were higher (p less than 0.01) in the Ms than in Lw piglets and those of adrenaline were lower (p less than 0.01) in the Ms Lw piglets and those of adrenaline were lower (p less than 0.01) in the Ms piglets. Breed had no significant effect on the response of plasma glucose, FFA and catecholamines during exposure to cold. At both ages of exposure, plasma concentrations of glucose and catecholamines were significantly increased. Plasma concentrations of FFA were increased (p less than 0.01) at 2 h, but at 24 h a decrease (p less than 0.01) was observed during cold exposure. Colostrum from Ms sows had greater concentration of lipids than that from Lw sows. It is suggested that the similar resistance to cold of the Ms and Lw piglets despite the lower body weight of the former is due, in part, to a greater availability of FFA as an energy source. PMID- 1873363 TI - Diet composition modifies embryotoxic effects induced by experimental diabetes in rats. AB - Despite improvements in prenatal care, the incidence of congenital malformations in diabetic pregnancies is still 3-4 times higher than in normal pregnancies. These defects could be attributed to alterations of intrauterine environment due to disorder of the maternal metabolism. If this were true, the quality of food could play a role in diabetes-induced embryotoxicity. To check this hypothesis, female CD rats were made diabetic by injecting intravenously 50 mg/kg of streptozotocin 2 weeks before mating. From the first day of pregnancy they were divided into three groups and maintained on the following diets: (1) standard diet (Italiana Mangimi); (2) purified high protein diet (protein 55%, carbohydrates 25.5%, fat 7.5%, fiber 4.5%, ash 7.5%); (3) purified normoprotein diet (protein 19%, carbohydrates 62.5%, fat 7.5%, fiber 4%, ash 7%). Nondiabetic pregnant females fed with standard diet served as negative control. No significant differences were observed in blood glucose levels among the groups (range 410-500 mg/dl). The group fed on normoprotein diet showed at term of pregnancy: (1) higher rate of resorptions; (2) lower fetal weight; (3) higher frequency of major malformations than the groups fed standard and hyperproteic diets. Although we are not able at this time to discriminate between a protective effect of a diet with a high protein content and a disruptive effect of a diet containing high quantity of carbohydrates, the results of this trial support the hypothesis of a fuel-mediated teratogenesis in diabetic pregnancy. PMID- 1873364 TI - Effects of maternal bilateral adrenalectomy and betamethasone administration on fetal rat encephalic development. AB - The present study examined the effects of maternal bilateral adrenalectomy and betamethasone treatment on fetal encephalic development, in terms of fetal body weight, brain weight, DNA, protein and lipid content and morphological development. Both influenced the developmental time patterns of fetal brain and cerebellum. Fetuses of adrenalectomized rats had decreased body weights, whereas brain weight was not affected. Maternal adrenalectomy produces in fetal brain a decreased number of cells and increased cell size, while betamethasone treatment of adrenalectomized rats increased cell number, which was not different from control values; cell size remained lower than in control fetuses. Lipid content was increased in the fetuses of betamethasone-treated rats. In terms of morphological development, laminated structures (hippocampus and brain and cerebellar cortex) were the ones most affected. PMID- 1873365 TI - Cerebral blood flow velocity regulation in preterm infants. AB - Cerebrovascular autoregulation is the mechanism by which changes in cerebral blood flow are prevented during fluctuations in mean arterial blood pressure. Doppler ultrasound measurement of cerebral blood flow velocity provides a reliable indirect technique to estimate cerebral blood flow. In 48 stable preterm infants less than or equal to 32 weeks gestation, we studied the mean flow velocity in the pericallosal artery at 12, or at 12 and 72 h of age with two dimensional/pulsed Doppler ultrasound and correlated the mean flow velocity with the simultaneously obtained mean arterial blood pressure values. Mean flow velocity was stable at a mean arterial blood pressure ranging from 31 to 40 mm Hg, but changed proportionally with mean arterial blood pressure values outside this narrow range. Multiple regression analysis showed that mean flow velocity was primarily determined by mean arterial blood pressure. These data suggest that in preterm infants regulation of cerebral blood flow velocity occurs only over a narrow range of mean arterial blood pressure values. PMID- 1873366 TI - Neonatal gastrointestinal growth and function: are they regulated by composition of feeds? AB - The effects of natural suckling versus a cow's milk formula on gastrointestinal growth and mucosal function were measured in newborn guinea pigs during the first 8 days of postnatal life. Comparable growth was achieved between the two groups. Both feeds appeared to be a stimulus for the growth of the gastrointestinal tract and expression of disaccharidases, but not for mucosal growth. Formula feeding was associated with a diminished rate of lactase expression and an enhanced rate of maltase and sucrase expression suggesting that the effect of natural suckling is regulatory, acting to delay expression of an inherent ontogenic programme uncovered by formula feeding. These finding in the precocial guinea pig contrast with those in the altricial rat, and have implications for our understanding of the regulation of gastrointestinal development and effects of formula feeds, in other species, including man. PMID- 1873367 TI - Hyperoxemia does not affect renal hemodynamics and function in newborn rabbits. AB - Renal hemodynamics and function were assessed in 10 anesthetized newborn rabbits undergoing acute hyperoxemia for 1 h. The hyperoxemic period either followed (group 1: n = 5) or preceded (group 2: n = 5) a normoxemic control period. Renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed by the clearance of p-aminohippuric acid and inulin, respectively. Urine flow rate, GFR, RBF, renal vascular resistance, filtration fraction and sodium fractional excretion remained unchanged throughout the study whatever the order of the normoxemic and hyperoxemic periods. It is concluded that hyperoxemia up to PaO2 of 170 mm Hg does not alter renal function. PMID- 1873368 TI - Size selectivity of lung protein accumulation in preterm ventilated lambs. AB - The 1-hour net accumulation of four labeled proteins of different sizes (6.5, 29, 69 and 150 kD) from the vascular space into the lungs and airspaces was measured in preterm ventilated lambs at 132 days gestational age. Lambs treated with Survanta, a surfactant prepared from bovine lung, were studied at 1, 3, 5 and 8 h after birth, while lambs not treated with this surfactant were studied up to 5 h of age because of severe respiratory failure. The labeled proteins were lost from the vascular space more rapidly over the first 1 h of life than at later times (p less than 0.01). Labeled protein recoveries were similar at 1 and 3 h in surfactant and control lambs and decreased by 8 h in surfactant-treated lambs (p less than 0.05). In both the surfactant-treated and control animals, there was a sequential decrease in labeled protein recoveries based on protein size (p less than 0.01). There was no change with time in size selectivity for accumulation of the labeled proteins into the lungs for either the control or surfactant-treated lambs, although surfactant treatments decreased accumulation of the 6.5 and 29 kD proteins at 5 h when compared to the control group (p less than 0.05). Labeled protein recoveries in alveolar washes demonstrated less size selectivity. These studies documented that size selectivity of the vascular endothelium did not change over the first 8 h of life in preterm ventilated lambs, a pattern that was not indicative of progressive lung injury. PMID- 1873369 TI - Genes, environment and psychopathology. PMID- 1873370 TI - Quantitative assessment of smooth pursuit gain and catch-up saccades in schizophrenia and affective disorders. AB - The smooth pursuit responses to 5 degrees and 20 degrees/sec constant-velocity stimuli were recorded from 23 patients with schizophrenia, 16 affective disorder patients, and 21 normals using low-noise infrared oculography. Pursuit gain, catch-up saccade (CUS) rate and amplitude, and their interrelationships were examined. Gain in the schizophrenic patients was reduced only at 20 degrees/sec, but for both patient groups, CUS rate at 5 degrees/sec was significantly lower than in normals. Using CUS rate at 20 degrees/sec, the patient groups could be distinguished from each other (the rate for schizophrenic patients being highest, and the rate for affectives the lowest) but neither differed significantly from normals. The diagnostic groups did not differ significantly in mean CUS amplitude, although there was a trend for patients to have larger saccades. Gain CUS rate correlation was strong in normals but reduced or absent in both patient groups. These results indicate that the ocular motor systems of patients with schizophrenia and affective disorders process eye position error abnormally. PMID- 1873371 TI - Pain sensitivity in anorexia nervosa and bulimia nervosa. AB - Pain threshold was measured with short heat stimuli using a contact thermode in 19 patients with anorexia nervosa, 20 patients with bulimia nervosa, and 21 control subjects. Both patient groups had significantly elevated pain thresholds compared with the control subjects. In the total sample, no substantial covariation could be demonstrated among pain threshold and clinical, physiological, metabolic, or psychological data. However, in separate regression analyses pain threshold correlated significantly (negatively) with local skin temperature in the anorectic patients and almost significantly (positively) with body weight in the bulimic patients. This finding suggests that the reduced pain sensitivity in the two kinds of eating disorders might have different causes. PMID- 1873372 TI - The impact of selenium supplementation on mood. AB - The possibility that a subclinical deficiency of the trace element selenium might exist in a sample of the British population was examined by giving a selenium supplement for 5 weeks. Using a double-blind cross-over design, 50 subjects received either a placebo or 100 mcg selenium on a daily basis. On three occasions they filled in the Profile of Moods States. A food frequency questionnaire was used to estimate the intake of selenium in the diet. Intake was associated with a general elevation of mood and in particular, a decrease in anxiety. The change in mood when taking the active tablet was correlated with the level of selenium in the diet, which was estimated from a food frequency questionnaire. The lower the level of selenium in the diet the more reports of anxiety, depression, and tiredness, decreased following 5 weeks of selenium therapy. The results are discussed in terms of the low level of selenium in the food chain in some parts of the world. PMID- 1873373 TI - Effects of subchronic d-amphetamine on prepulse and gap inhibition of the acoustic startle reflex in rats. AB - Prepulse inhibition of the startle reflex has been used as an animal model for information processing deficits found in some types of schizophrenia. These deficits may be mediated by hypersensitive dopaminergic systems. In the present study, the effects of subchronic d-amphetamine administration [2 mg/kg intraperitoneally (IP)] on prepulse and gap inhibition of the startle reflex were compared to the effects of acute amphetamine and saline administration on startle inhibition. Results of three experiments are reported. The first two experiments were used to select prestimulus parameters sensitive to changes in stimulus intensity on the one hand, and prestimulus parameters sensitive to temporal aspects of stimulus processing on the other hand. Because schizophrenics have problems with the temporal sequencing of information, prestimulus inhibition of the startle reflex was expected to be more pronounced when prestimulus processing depended predominantly upon temporal factors. Results supported this hypothesis, although the effects of d-amphetamine were found at near detection threshold duration only. Subchronic amphetamine had no effect on the neuronal mechanisms underlying inhibition of the startle reflex by prestimuli. The results also suggested that a careful selection of duration and intensity of the prestimulus may increase the sensitivity of the prestimulus-startle paradigm for the effects of drugs, for example. PMID- 1873374 TI - Sleep deprivation therapy. AB - This review reports, with as much detail as possible, on the literature relating to therapeutic sleep deprivation (or induced-wakefulness therapy) since it was first described in 1971. The antidepressive effect of sleep deprivation has been substantiated by numerous studies. A series of clinical predictors of response to sleep deprivation are also described. Partial sleep deprivation late in the night is equivalent to total sleep deprivation in terms of therapeutic value and- because of its simpler application--can be regarded today as the sleep deprivation method of choice. The status of sleep deprivation in the overall treatment schedule for depressive disorders is discussed in detail. Numerous findings, some of them contradictory, have been published on the effect of sleep deprivation on biological variables. To date, no unequivocal explanation has been found for the mechanism of action of sleep deprivation. PMID- 1873375 TI - Initial investigation of the left temporoparietal region in schizophrenia by 31P magnetic resonance spectroscopy. PMID- 1873376 TI - Timing of phototherapy and occurrence of mania. PMID- 1873377 TI - What is psychiatry? PMID- 1873378 TI - Effect sizes of P300 in schizophrenics. PMID- 1873379 TI - Comparison of intracellular and secreted isoforms of bovine and ovine luteinizing hormone. AB - The media (secreted isoforms) and tissue extracts (intracellular isoforms) from ovine and bovine pituitaries perifused in vitro were chromatofocused to examine the pattern of LH isoforms secreted. At slaughter, anterior pituitaries from castrated male cattle (n = 6) and sheep (n = 4) were collected, sectioned mid sagitally, and weighed. One half was immediately frozen and used to assess intracellular isoforms of LH. The remaining half was sliced and perifused for 120 min to allow attainment of a stable basal secretion rate and then stimulated with 5 x 10(-8) M LHRH. Effluent samples were collected and assayed for LH. Samples representing basal or LHRH-induced secretion were pooled, dialyzed against water, and lyophilized. Pituitary extracts were desalted by flow dialysis against water. All samples were chromatofocused on pH 10.5-7.0 gradients, and concentrations of LH in eluant fractions were determined by RIA. LH in pituitary extracts resolved into nine peaks, which were coded with letters beginning with the most basic isoform. Isoforms A, B, and C were nondetectable (bovine; p less than 0.01) or constituted a smaller percentage of total LH (ovine; p less than 0.05) in perifusates compared to intracellular samples. The percentages of isoforms D and E were lower (p less than 0.05) in perifusates than in intracellular samples from the ovine extracts but similar for the bovine (p greater than 0.05). Isoforms F and G were proportionately higher (p less than 0.05) in basal (bovine) and LHRH induced (bovine and ovine) samples than in intracellular samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873380 TI - Hypoxanthine-maintained two-cell block in mouse embryos: dependence on glucose and effect of hypoxanthine phosphoribosyltransferase inhibitors. AB - The culture conditions under which hypoxanthine maintains a two-cell block in preimplantation mouse embryos were assessed. Hypoxanthine prevented embryo development past the two-cell stage at concentrations as low as 30 nM, and this inhibitory activity required the presence of D-glucose. The action of hypoxanthine plus D-glucose was reversed by glutamine and higher lactate. D mannose substituted for D-glucose in supporting the inhibitory action of hypoxanthine, but L-glucose, D-fructose, and 2-deoxyglucose were much less effective. Other purine derivatives such as inosine and adenosine, but not xanthosine or uric acid, also blocked development at the two-cell stage at a concentration of 30 microM, and guanosine was inhibitory at higher doses. Assays of hypoxanthine phosphoribosyltransferase (HPRT) activity in lysates of four-cell embryos determined that the drugs 6-mercapto-9-(tetrahydro-2-furyl)-purine (MPTF) and 6-mercaptopurine (6-MP), but not 6-azauridine (6-AzaU), prevented salvage of hypoxanthine. In addition, MPTF and 6-MP produced a significant two-cell block, which did not depend upon the presence of hypoxanthine or D-glucose; whereas 6 AzaU was without effect. When embryos were cultured 2 days in the presence or absence of D-glucose, hypoxanthine salvage was significantly reduced in lysates of four-cell embryos exposed to D-glucose. D-glucose had no effect when added directly to the assay mixture. These data demonstrate that the ability of hypoxanthine to block embryo development at the two-cell stage depends on the presence of D-glucose or other glycolyzable sugars and suggest that inhibition of the purine salvage pathway promotes the two-cell block. PMID- 1873381 TI - Effects of exogenous steroids on androgen receptors in fetal guinea pig brain. AB - We treated pregnant guinea pigs on Day 50 of gestation with 10 mg testosterone propionate (TP), obtaining fetuses 2, 4, 8, or 18 h later as well as after 5 days of treatment. In a second group of pregnant guinea pigs, dihydrotestosterone propionate (DHTP), estradiol benzoate (E2B), progesterone (P), or cortisol was given 2 h before obtaining fetuses. Although TP treatment elevated fetal serum T (p less than 0.05), brain cytosolic androgen receptor (ARc) content was unchanged in fetuses of either sex. In female fetuses, nuclear androgen receptors (ARn) increased 10-fold in medial-basal hypothalamus (MBH) and preoptic area (POA) at 2 and 4 h (respectively) after treatment, while fetal male ARn content was unchanged. Maternal injection of other steroids (E2B, P, or cortisol, but not DHTP) significantly increased these hormones in the fetus 2 h later (p less than 0.05). Only androgens affected fetal androgen receptor (AR) content. While TP increased ARn in female MBH, DHTP decreased ARc in fetal anterior pituitary of both sexes. In this latter case, a metabolite of DHT may mediate the effects. We conclude that T crosses the guinea pig placenta and activates ARn in POA and MBH of female fetuses; male ARn appear to be maximally occupied by endogenous T. Steroids of other classes do not induce AR responses in fetal guinea pig brain. These AR changes may represent an initial cellular mechanism in brain sexual differentiation. PMID- 1873382 TI - Endometrial surface and secretory alterations associated with embryonic mortality in gilts administered estradiol valerate on days 9 and 10 of gestation. AB - Administration of estrogen to gilts on Days 9 and 10 of pregnancy results in total embryonic loss by Day 18. The present study examined changes in the uterine endometrial surface and secretion during conceptus attachment in control and estrogen-treated (Days 9 and 10) pregnant gilts. Gilts were unilaterally hysterectomized on either Days 12 and 14 or Days 16 and 18 of gestation. Uterine horns were flushed with saline and conceptuses were evaluated. Intact conceptuses were recovered from all control gilts, whereas estrogen-treated gilts contained normal intact conceptuses only on Day 12 of gestation. Antiviral activity, which reflects conceptus viability, was reduced (p less than 0.01) in uterine flushings after Day 14 in estrogen-treated gilts. Culture of endometrial explants with [3H]glucosamine revealed several glycoproteins that are synthesized during the period of conceptus attachment; however, no difference in glycoprotein synthesis between treatment groups was detected by analysis with two-dimensional PAGE and fluorography. Analyses of the uterine epithelium by scanning and transmission electron microscopy demonstrated that estrogen administration caused an alteration in the uterine surface, a thinning of the uterine epithelial glycocalyx, and a reduction of cationic ferritin binding to the microvilli of the uterine epithelium. Results indicate that conceptus mortality after early administration of estrogen is associated with alterations in the uterine endometrial surface during the period of conceptus attachment in the pig. PMID- 1873383 TI - Determination of the capacity of ram epididymal and ejaculated sperm to undergo the acrosome reaction and penetrate ova. AB - An understanding of epididymal maturation of sperm requires descriptions of changes in membrane properties and their relation to changes in cell function. While sperm membranes have been studied in some detail in rams, few reports address associated functional changes. This report provides such data by evaluating (a) the time course of sperm acrosome reaction (AR) induction for cells from each epididymal region; (b) the capacity of epididymal sperm to penetrate ova; (c) differences in physiological AR and general sperm degeneration; and (d) acrosin release of epididymal sperm. Ram epididymal (caput, corpus, and proximal and distal cauda) and ejaculated (EJ) sperm were incubated in vitro to assess their capacity to undergo an AR. Light microscopy revealed that in sperm populations which had traversed the proximal cauda epididymidis, greater than or equal to 50% exhibited an endogenous AR in less time (less than 17 h) than did sperm isolated from more proximal regions of the epididymis (22 greater than 50 h). Heparin added to sperm did not stimulate the AR in epididymal or EJ sperm, whereas addition of a calcium ionophore (A23187) increased AR rates for cauda and EJ sperm, but not caput or corpus sperm. A second experiment evaluating percent AR, percent motile cells, and percent hamster ova penetrated revealed that sperm isolated from regions proximal to the cauda epididymidis failed to penetrate ova. When cauda or EJ sperm exhibited motility greater than 5% and AR greater than 24%, penetration of hamster eggs occurred. Comparisons of acrosomal integrity by electron or light microscopy were not different for sperm at any stage of epididymal maturation, suggesting that minimal nonspecific membrane changes occur and that light microscopy is valid for evaluating the acrosomal status of ram spermatozoa. Acrosin activity (sperm bound and dissociated) also was measured. Both total activity and release of acrosin from sperm to the medium during an 8-h incubation was greater for mature than for immature sperm. Results from these experiments are discussed in relation to the changes that must occur in sperm as they acquire the capacity to undergo an AR and penetrate hamster ova. PMID- 1873384 TI - Effect of dilauroylphosphatidylcholine liposomes on motility, induction of the acrosome reaction, and subsequent egg penetration of ram epididymal sperm. AB - The effects of dilauroylphosphatidylcholine (PC12) on ram epididymal sperm motility, acrosome reaction (AR) induction, plasma membrane permeability, mitochondrial function, and sperm penetration into zona-free hamster eggs were determined. PC12 (50 microM) induced cell motility in caput and cauda sperm, as measured by subjective estimation and automated motility analysis. Motion parameters of treated caput sperm approached those of control ejaculated sperm. Flow cytometric analysis revealed that membrane permeability to propidium iodide and mitochondrial uptake of rhodamine 123 changed during epididymal transit. PC12 induced the AR in sperm from all epididymal regions relative to control incubated sperm (caput 17% vs. control 8%; corpus 29% vs. control 13%; proximal cauda 48% vs. control 4%; distal cauda 51% vs. control 9%). After PC12 treatment, egg penetration by sperm was increased for sperm from the corpus (corpus 7% vs. control 0%) and cauda (proximal 48% vs. control 0%; distal 51% vs. control 0%), but not for caput sperm (caput 0% vs. control 0%). These studies establish that some sperm in each region of the epididymis possess the capacity for movement and the AR. Caput sperm, however, were unique in that they could not penetrate eggs. Additional maturational changes must occur in the caput and/or corpus epididymidis before penetration capacity can be expressed. PMID- 1873385 TI - In vitro development of rabbit pronuclear embryos in rabbit peritoneal fluid. AB - The use of rabbit peritoneal fluid (PF) for the culture of rabbit embryos in vitro was evaluated. Development of zygotes cultured in PF and Earle's balanced salts solution (EBSS) + 10% fetal calf serum (EBSS/FCS) was compared. The effects of increasing the concentration of PF in EBSS and of culturing embryos in fractionated PF were also investigated. In addition, embryonic development in PF was compared to that in vivo. Development to hatching blastocysts was enhanced with PF (73%) compared to EBSS/FCS (3%, p less than 0.001). PF manifested greater mitogenic activity than EBSS/FCS, as indicated by higher cell number in embryos at 48, 72, and 96 h post-mating/hCG (p less than 0.001). PF also promoted blastocyst cell proliferation in a dose-dependent manner (r = 0.98, p less than 0.01); however, embryo growth remained slower than in vivo. Culture in the high (greater than 30,000 Da) molecular mass fraction of PF reduced incidence of hatching (56% vs. 92%, p less than 0.001) and mean cell number in Day 4 blastocysts (151 +/- 4 vs. 243 +/- 5, p less than 0.001). Rates of blastocyst hatching (10%) and cell number (110 +/- 3) were further reduced in the low (less than 30,000 Da) molecular mass fraction. When the high molecular mass fraction was dialyzed, embryos did not develop beyond the early morula stage. This suggests that the interaction or the synergy of high and low molecular mass components of PF is necessary for optimum development of rabbit embryos. PMID- 1873386 TI - Role of epithelial cells of the male excurrent duct system of the rat in the endocytosis or secretion of sulfated glycoprotein-2 (clusterin). AB - The localization of sulfated glycoprotein-2 (clusterin; SGP-2) was investigated in the rete testis, efferent ducts, and epididymis of the rat using light (LM) and electron (EM) microscope immunocytochemistry. At the LM level, the epithelial cells of the rete testis and efferent ducts demonstrated an intense immunoperoxidase reaction over their apical and supranuclear regions, and sperm in the lumen of the efferent ducts were unreactive. In the EM, gold particles were found exclusively over the endocytic apparatus of these cells. In the proximal area of the epididymal initial segment, an insignificant immunostaining of epithelial cells and sperm was observed. However, the distal area of the initial segment showed a moderate staining over the epithelial principal cells and sperm, while in the intermediate zone of the epididymis a stronger reaction was observed over these cells. The strongest immunoperoxidase reaction was noted in the caput epididymidis, where it formed a distinct mottled pattern. Thus, while some principal cells were intensely stained, others were moderately or weakly stained; a few were completely unreactive. In the corpus and cauda epididymidis, the staining pattern was similar but not as intense. In the EM, only the secretory apparatus of these cells was found to be immunolabeled with gold particles. Sperm in the lumen of these different regions were also labeled. The epithelial clear cells were unreactive throughout the epididymis. Northern blot analysis substantiated these results and showed the presence of highest levels of SGP-2 mRNA in the caput epididymidis, especially in its proximal area, whereas increasingly lower levels were found in the corpus and cauda epididymidis. In summary, these results suggest that testicular SGP-2 dissociates from the sperm during passage through the rete testis and efferent ducts, where it is endocytosed by the epithelial cells lining these regions. In the epididymis, it is replaced by an epididymal SGP-2 that is secreted by the epithelial principal cells of the epididymis. Furthermore, in the epididymis, the principal cells appear to be in different functional states with respect to the secretion of epididymal SGP-2 within a given region of the duct as well as along the epididymal duct. PMID- 1873387 TI - Immunocytochemical localization of relaxin in human corpora lutea: cellular and subcellular distribution and dependence on reproductive state. AB - Relaxin is one of the hormones present during pregnancy and it is synthesized primarily by corpora lutea (CL). Other reproductive tissues including CL of the menstrual cycle may also synthesize this hormone. Very little is known, however, about the cellular and subcellular distribution of relaxin in human CL and dependence of luteal relaxin on the reproductive state. The light and electron microscope immunocytochemical studies described here were undertaken to obtain this information using antisera to porcine and human relaxin. Immunostaining was found in large luteal cells (17-30 microns) but not in small luteal cells (7-16 microns) or in nonluteal cells in any of the reproductive states or in human hepatocytes. Luteal immunostaining was low in early luteal phase; it increased progressively, reaching the highest level in late luteal phase, and then decreased greatly in corpora albicantia. Term pregnancy CL contained similar immunostaining as early luteal phase CL. Mid luteal phase CL contained more immunostained cells than late luteal phase CL, but the late luteal phase CL contained a greater amount of immunostaining per cell than mid luteal phase CL. The immunogold particles due to relaxin were primarily present in secretory granules and to a small extent in rough endoplasmic reticulum. Quantitation revealed that secretory granules contained a much higher number of gold particles than did rough endoplasmic reticulum. These two organelles from late luteal phase CL contained greater numbers of gold particles than those from mid luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873388 TI - Quantitative cell composition of human and bovine corpora lutea from various reproductive states. AB - The cell composition of human and bovine corpora lutea (CL) from various reproductive states was investigated by computerized video-based interactive Bioquant image analysis system IV and by light microscope immunocytochemistry. Human and bovine CL contained more nonluteal cells than luteal cells. Human CL contained a lower number of luteal and a greater number of nonluteal cells than bovine CL. Regardless of the reproductive state, human CL contained more small luteal cells than large luteal cells. In all reproductive states except in the late luteal phase, the bovine CL also contained more small luteal cells than large luteal cells. The average sizes of all the cells in human CL were smaller than in bovine CL. Human CL contained more vascular space than bovine CL during mid and late luteal phases. The number of luteal cells increased and nonluteal cells decreased from early to mid luteal phase, and then luteal cells decreased and nonluteal cells increased in late luteal phase and in degenerating human and bovine CL. While the change of number of small and large luteal cells first occurred from early to mid luteal phase in human CL, it did not take place until the late luteal phase in bovine CL. The average size of large luteal cells in humans and of small luteal cells in cattle did not change, whereas size of the other cells changed in different reproductive states in both human and bovine CL. The cell composition of term pregnancy human CL was similar to mid or late luteal phase, whereas the cell composition of early pregnancy bovine CL was similar to mid luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873389 TI - Theca cells may be present at the outset of follicular growth. AB - Opinions differ concerning when theca cells arise during follicular growth. Theca cells cannot be distinguished from ovarian stroma cells on the basis of morphology alone. However, long-term continuous infusion of [3]thymidine (3H-TdR) thoroughly labels theca cells of large and medium-sized follicles whereas most stromal cells remain unlabeled. The objective of this study was to determine when, during the course of follicular development, labeled, squamous cells located just outside the follicular basement membrane (putative theca cells) first become apparent. Rats were given infusions of 3H-TdR for various periods of time. Autoradiographs were prepared from 2-microns-thick plastic sections of ovaries. Morphologically recognizable theca cells of large and medium-sized follicles were sharply delineated from surrounding stroma cells by their labeling pattern. Although unilaminar follicles lacked morphologically distinct theca layers, they all were closely enveloped by labeled cells just outside the basement membrane. Follicles with a few as 4-5 granulosa cells in cross section often had labeled cells on the convex surface of their basement membranes. These observations suggest the possibility that theca cells may already be present at the very outset of follicular growth. PMID- 1873390 TI - Oxytocin stimulates progesterone release from microdialyzed bovine corpus luteum in vitro. AB - A microdialysis system (MDS) was implanted in corpora lutea (CL) from cows (Days 5-7, 8-12, and 15-18 of the estrous cycle); the CL were maintained in organ culture chambers. With this system, active substances can be applied, and a collection of steroids released from luteal cells surrounding the microcapillary (cut-off point = 100 kDa) is possible, while luteal cells maintain cell-to-cell contact. Spontaneous pulses of progesterone release were observed in 90% of control (perfused with Ringer's solution only) at 60-80 min intervals. The infusion of bovine LH (bLH) for 20 min (0.1-10 micrograms/ml) stimulated dose dependent release of progesterone. Both results indicate that the CL maintains the activity of progesterone release and the ability to respond to LH stimulation in this system. Oxytocin (1-100 microM) also stimulated progesterone release in a dose-dependent manner. Preexposure with oxytocin antagonist blocked the stimulatory effect of oxytocin (p less than 0.01) but not of LH (p less than 0.05), confirming the specificity of the effect. When CL were prestimulated with a low dose of oxytocin (1 microM, 20 min) twice before bLH application, the release of progesterone by bLH (1 micrograms/ml, 20 min) was more pronounced (p less than 0.05). A long-term infusion (3 h) with oxytocin and/or bLH stimulated the release of progesterone for the whole period of time. Oxytocin was most stimulative during the early luteal phase (Days 5-7) and decreased continuously from Days 8-12 to Days 15-18.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873391 TI - Requirement of innervation for maintenance of structural and functional integrity in the rat prostate. AB - The rat prostate is innervated by pelvic and hypogastric nerves through a single pelvic ganglion, removal of which would result in complete denervation of the prostatic complex. The present study was conducted to investigate the effect of denervation on the rat prostate. Adult Sprague-Dawley rats of 300 g in body weight were divided into two groups. Bilateral pelvic ganglion denervation was performed in one group of animals; the other group received a sham operation. Three weeks later, animals were killed; and the ventral prostates were removed, weighed, and subjected to routine procedures for light and electron microscopy. The average weight, total protein content, and total content of acid phosphatase of the ventral prostates in the denervated group were significantly less than those in the control group. Total DNA content per prostate, however, was not significantly different between the two groups. Results of histological examination indicated that the prostates from control animals showed normal morphology, whereas those from the denervated animals showed reduced cell height and enlarged vacuoles surrounding the nuclei. Inspection of electron micrographs revealed that the prostates from denervated animals, compared with those of controls, showed a reduced ratio of cell height:cell width, which is associated with a reduced number of microvilli and secretory granules. These results indicate that denervation in the prostate is associated with a lower prostatic weight, decreased cell height, and reduced secretory activity. PMID- 1873392 TI - In vitro fertilization of goat oocytes. AB - Experiments were carried out to achieve fertilization (IVF) and initial embryonic development of goat oocytes in vitro. Oocyte/cumulus complexes were recovered from large follicles (greater than 7 mm) of hormonally treated doses and from 1-6 mm follicles of ovaries from hormonally superstimulated and nontreated goats. Three different sperm treatment/IVF media were used: defined medium (Brackett and Oliphant, Biol Reprod 1975; 12:260-274) with modifications (mDM); TALP (Bavister and Yanagimachi, Biol Reprod 1977; 16:228-237), as modified by Parrish et al. (Theriogenology 1986; 25:591-600), i.e. modified TALP (mTALP); and HEPES-buffered M199 with modifications (mH-M199). Immature oocytes (from 1-6 mm, small antral follicles) were cultured for in vitro maturation (IVM) in M199 buffered with bicarbonate and with modifications including supplementation with 20% (v/v) goat serum (mB-M199) with either (a) 100 micrograms LH/ml, (b) 5 micrograms FSH/ml, or (c) no added gonadotropin control. Insemination of (in vivo or in vitro) matured oocytes was performed with swim-up separated and heparin-treated freshly ejaculated sperm; additionally, caffeine was included in the mDM treatment. Use of mDM yielded better results than mTALP or mH-M199 (p less than .05). Results with oocytes after IVM were significantly better than those obtained with oocytes matured in vivo (68.4% vs. 45.5%, p less than 0.05). Presence of LH or FSH during oocyte maturation improved both the IVM and IVF results over those of the control (p less than 0.05). The highest proportion of fertilized oocytes (fertilization rate) was achieved by combining the use of mDM for sperm and IVF with IVM in the presence of LH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873393 TI - Characteristics of a genetic polymorphism for reproductive photoresponsiveness in the white-footed mouse (Peromyscus leucopus). AB - Wild populations of Peromyscus are often composed of individuals that vary greatly in their reproductive response to photoperiod. A population of white footed mice (P. leucopus) from Michigan (43 degrees N) was subjected to mass selection in the laboratory both for and against reproductive photoresponsiveness for four generations. The first generation of selection yielded one line of mice in which about 80% of the individuals were classified as reproductively photoresponsive (i.e., with undeveloped reproductive tracts when reared in short days, 8L: 16D) and another in which only about 20% were reproductively photoresponsive. Some and perhaps most of this difference was accounted for by changes in degree of responsiveness to photoperiod rather than by alterations in the proportion of discrete responsive vs. unresponsive phenotypes. Alteration of critical day length was not a factor. Three more generations of selection failed to change the proportions noted above significantly. Although the genetic control of reproductive photoresponsiveness is undoubtedly complex, a single variable locus may be responsible for much of the heritable variation present in this population. These results also suggest that natural populations contain genetically determined phenotypes that are intermediate between absolutely photoresponsive and absolutely unresponsive. The factors that might promote maintenance of heterogeneity of reproductive photoresponsiveness in a wild population of rodents are considered. PMID- 1873394 TI - The energetic regulation of ovulation: a realistic role for body fat. AB - This review weighs the evidence for and against the hypothesis that ovulation is regulated by a critical amount of body fat. The evidence supporting this hypothesis is correlative, and most of it stems from observations made in humans. On balance, the evidence from human studies does not support the hypothesis, however, and the results of animal studies argue strongly against it. In the latter regard, a variety of experimental approaches have been tried in both adult and peripubertal females of several species, and the results almost uniformly show little relationship between fatness and ovulation. There is no doubt that ovulation can be regulated somehow in relation to whole-body energy balance and that fat stores are an important component of energy balance, but there is no reason to accord body fat a direct causal role in regulating ovulation. PMID- 1873395 TI - Testosterone and estradiol potentiate the serum gonadotropin response to gonadotropin-releasing hormone in goldfish. AB - The effects of gonadal steroids on gonadosomatic index (GSI; gonad wt/total body wt x 100), pituitary gonadotropin (GTH) content, and serum GTH response to [D Ala6,Pro9-Net]-luteinizing hormone-releasing hormone (LHRH-A) were investigated throughout the seasonal reproductive cycle of the goldfish. Gonad-intact female fish were implanted i.p. for 5 days with silastic pellets containing no steroid (blank), testosterone (T; 100 micrograms/g), or estradiol (E2; 100 micrograms/g). The serum GTH response at 6 h following i.p. injection of saline or 0.1 microgram/g LHRH-A was assessed. In blank-implanted, saline-injected animals, seasonal variations in GSI, pituitary GTH content, and serum GTH levels were evident; maximal and minimal levels were noted in the spring and summer months, respectively. In blank-implanted fish, LHRH-A effectively stimulated GTH release in females undergoing gonadal recrudescence (late autumn and winter) and in sexually mature (spring) females, but not in sexually regressed (summer and early autumn) females. Implantation of T or E2 raised serum steroid levels to those found during ovulation in goldfish. Steroid treatments did not affect unstimulated serum GTH levels at any time of the year. Testosterone effectively potentiated the serum GTH response to LHRH-A during the entire reproductive cycle, whereas the positive effects of E2 were evident in sexually regressed and post-spawning females only. Both T and E2 potentiated the GTH response to LHRH-A in male fish. To examine the involvement of T aromatization in mediating its actions on induced GTH secretion, male and female fish were implanted with T or the nonaromatizable androgens 5 alpha-dihydroxytestosterone (DHT; 100 micrograms/g) and 11-keto-testosterone (11-KT; 250 micrograms/animal). Testosterone potentiated the GTH response to LHRH-A in both males and females whereas DHT and 11-KT were without effect. Furthermore, the positive action of T on induced GTH secretion was blocked by 2-day pretreatment with the aromatase inhibitor 1,4,6-androstatrien-3,17-dione (100 or 300 micrograms/g). Multiple i.p. injections of hCG (0.2 microgram/g every 3 days for 39 days), probably through stimulation of endogenous T secretion, resulted in potentiation of the GTH response to LHRH-A in mature male goldfish. These results clearly demonstrate that T, through aromatization to E2, can increase pituitary responsiveness to exogenous LHRH-A in gonad-intact male and female goldfish. PMID- 1873396 TI - Nutritional anestrus in beef cows: effects of body condition and ovariectomy on serum luteinizing hormone and insulin-like growth factor-I. AB - The objectives of this experiment were to determine if a postcastration increase in concentrations of LH occurs in nutritionally anestrous beef cows and to examine the relationship between body energy reserves and secretion of LH and insulin-like growth factor-I (IGF-I). Nonpregnant, nonlactating, Hereford cows were fed to maintain (M) body weight (BW), body condition score (BCS), and normal estrous cycles (n = 5) or were fed a restricted (R) diet for 26 wk to lose BW and BCS and to become anestrus (n = 10). At 5-7 wk after the initiation of anestrus, R cows were randomly allotted to be ovariectomized (OVX) via flank incision (n = 5) or to remain intact (INT, n = 5). OVX was performed when R cows became anestrous. All M cows were OVX. Serum was collected frequently the day before and during the first 10 days after OVX, and concentrations of progesterone, estradiol, LH and IGF-I were quantified. On Day 10 after OVX, 1 mg of estradiol was injected into 3 cows from each group and serum was collected for 30 h. After OVX, there was a treatment-by-day effect for mean serum LH and IGF-I concentrations. Concentrations of LH increased (p less than 0.01) and concentrations of IGF-I decreased (p less than 0.05) in M-OVX cows when compared with R-OVX and R-INT cows. Concentrations of LH and IGF-I were similar for R-OVX and R-INT cows. The number of LH pulses was similar for M and R cows.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873397 TI - Photoperiod regulation of uterine activity and melatonin rhythms in the pregnant rhesus macaque. AB - This study tested the hypothesis that photoperiod phase entrains the daily rhythms in myometrial contractility and melatonin in circulation in the pregnant rhesus monkey during late gestation. Six chronically catheterized rhesus macaques were maintained on a 12L: 12D cycle (lights-on, 0700 to 1900 h). Intrauterine pressure was continuously recorded throughout the study. At 120-135 days of gestation, blood samples were collected at 3-h intervals over a 24-h period beginning 2 h after lights-on at 0900 h. We observed a characteristic nocturnal uterine activity rhythm; contractile events peaked at 2300 h compared to the nadir at 0900 h (p less than 0.05, ANOVA). Daytime plasma melatonin levels averaged 31 +/- 6 pg/ml compared to the nocturnal peak of 60 +/- 6 pg/ml at 2400 h (p less than 0.05). Photoperiod was then shifted 11 h so that lights were on from 2000 to 0800 h. After 7 days, blood samples were again collected over 24 h, beginning 2 h after lights-on at 2200 h; this sampling protocol was repeated at weekly intervals until delivery. After 7 days of reversed photoperiod, the peak in the uterine activity shifted to 1100 h, whereas the nadir occurred at 2200 h (p less than 0.05). Melatonin concentrations increased from a mean of 22 +/- 4 pg/ml during the light phase to a nighttime peak of 60 +/- 5 pg/ml at 1300 h (p less than 0.01). A similar and stable phase relationship to lights-off was maintained for both the myometrial activity rhythm and the circadian melatonin rhythms after reversed photoperiod.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873398 TI - Prolactin levels in the western spotted skunk: changes during pre- and periimplantation and effects of melatonin and lesions to the anterior hypothalamus. AB - Prolactin (PRL) is the primary pituitary hormone responsible for initiating increased function of the corpus luteum and blastocyst implantation in the western spotted skunk. Therefore, we have designed experiments to validate a PRL RIA, characterize the preimplantation profile in PRL secretion, and determine the effects of exogenous melatonin and lesions to the anterior hypothalamic area (AHA) on PRL secretion in the skunk. These objectives were investigated with a heterologous RIA using canine PRL standards and antiserum. Displacement curves of skunk pituitary extract and serum were parallel to the canine PRL standard curve. Growth hormone-releasing hormone injection did not cause a significant change in plasma PRL levels as detected by the assay (p = 0.74). Injection of pimozide increased and bromocriptine decreased plasma PRL levels (p less than 0.05). A seasonal trend in plasma PRL levels was observed during the preimplantation period, with mean concentrations ranging from 5 ng/ml during the period of short day length in January to 17.1 ng/ml during the long day photoperiod in early May. The average date of blastocyst implantation in this study was 2 May (n = 16). Silastic capsules containing melatonin (n = 5) significantly delayed both the seasonal rise in plasma PRL levels and the time of implantation (p less than 0.05) compared to controls with empty capsules (n = 4). Lesions to the AHA (AHAx, n = 5) eliminated these effects of melatonin on both the rise in PRL and time of implantation. PRL levels were highly correlated with progesterone levels (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873399 TI - Attachment of boar sperm to mucosal explants of oviduct in vitro: possible role in formation of a sperm reservoir. AB - Ejaculated boar sperm were incubated with explants of porcine oviductal mucosa that had been dissected from the isthmic and ampullar regions of gilts. Sperm bound within minutes to the epithelial surfaces of the explants. Binding was not affected by region (isthmus or ampulla) nor day of estrous cycle (Day 0 or Day 10), but was increased by addition of 70 pg/ml 17 beta-estradiol to the medium. Scanning electron micrographs indicated that sperm bound, via the acrosomal region, to ciliated cells. After 24 h, the numbers of bound sperm dropped significantly, but the motility of the bound sperm did not. A mucous material that entrapped sperm was observed on the epithelial surfaces of 23/32 isthmic and only 4/32 ampullar explants. These results indicate that sperm sticking to ciliated cells and mucus can create a sperm reservoir in the isthmus, but the means by which sperm are released remain unknown. PMID- 1873400 TI - [The plaque wet weight in subjects with different caries involvement]. AB - Determinations of the wet weight of 48 h human dental plaque have proved that there is a significantly higher plaque wet weight among patients characterized by a low caries experience compared to patients with a high caries experience. The plaque-forming rate of patients with a low caries experience rises with advancing years. PMID- 1873401 TI - [The establishment efficiency of S. sobrinus OMZ 176 in a model caries experiment on the Osborne-Mendel rat]. AB - S. sobrinus OMZ 176 was inoculated in young OM rats during tooth eruption in two experiments and the microbial composition of dental plaque as well as the caries decay was estimated after 25 days on cariogenic sucrose rich diet. Germs were reproducibly established in the oral cavity by such way. The resulting caries decay correlated with the streptococci in the dental plaque. Due to this fact it seems to be necessary to identify not only the inoculated microorganisms at the end of each animal experiment but also to estimate the qualitative composition of the whole dental flora which may have an essential cariogenic effect. PMID- 1873402 TI - [Teleroentgenographic findings in adults with overbite. Teleroentgenographic morphology in closed-bite patients]. AB - Lateral skull radiographs were analyzed in twenty patients with retroclined incisors. Greatest deviations from the comparison values were found in the region of the lower face. The mandible shows a retrognathic and counter clockwise rotated position. The height of the anterior lower face height and the dentoalveolar height are reduced. The interincisor angle ist distinct increased. Etiological aspects and the therapeutical consequences of the findings are mentioned. PMID- 1873403 TI - [Clinical indices in periodontal diagnosis. A review]. AB - In this review, are described the most common clinical indices. Further, is discussed and criticized their application as well as usefulness in the clinical diagnosis and patient management. Although, there exists a variety of clinical indices, only a few of them could be sufficient for monitoring diagnosis and treatment in the general practice. PMID- 1873404 TI - [Alginate with a chlorhexidine admixture in a torsion test]. AB - The elastic properties of commercial alginate impression materials are not essentially influenced by chlorhexidin at microbiologically effective concentration. The torsion test proved to be a simple reliable method. PMID- 1873405 TI - [Restorative materials and initial pellicle formation]. AB - Information concerning initial pellicle forming (dental cuticle) are possible via contact-angle determination. Not only the type of the restorative material but also its surface processing (structure) influence the initial forming of the pellicle. The higher the surface energy of a material, the more complete and quicker the masking of the surface by the initial pellicle. PMID- 1873406 TI - [The light-cured composite CuRAY-FIL. A clinical and experimental animal study]. AB - This article presents a animal study on 36 teeth by dogs without definite race. By the histological observation we cannot assess a damage of the pulp by application of CuRAY-FIL with a basic material. The clinical and REM observations after 11 and 24 months by 76 patients pointed out: CuRAY-FIL has a good colour stability and adhesion, however the claims on a optimal filling material for the restoration in the visible area are not accomplished in all points. PMID- 1873407 TI - [Trace element studies on the the dental calculi of individuals from historical populations]. AB - In two different populations (Bavaria 6th-7th cent. A.D. and Egypt 700 B.C. till 400 A.D.) calculus was analysed in order to find hints for the nutrition of these people. All together, the concentration of 23 elements were analysed. The first dates showed that there were high significant differences in 8 elements (Al, Ba, Ca, Cr, Fe, K, Mn, Sr). The enormous variation of the element concentration as well as the huge of elements allows finally interpretations not in this state. It will be the aim of further studies. PMID- 1873408 TI - [Sediments on the inner surfaces of the tube of spray-mist suction devices]. AB - Spray mist suction tubes made of polyvinylchloride were examined. Qualitative and quantitative germ determinations of the tube inner surfaces were carried out. To make reproducible examinations a standardized method of germ determination was introduces. Macroscopical model tests, assessments by scanning electron microscopy and chemical analyses dealt with the genesis of the deposits and bacterial coatings in the inner tube. A method has been found which minimizes coating formation by spraying of a contaminating cleaning agent. PMID- 1873409 TI - [The importance of Pneumocystis carinii infection in patients with acute respiratory distress syndrome]. AB - Each year we treated approximately 40 patients with adult respiratory distress syndrome (ARDS) in our department of anaesthesiology. In these cases we found with bronchoalveolar lavage followed by microbiological examination, a high incidence (40 per cent) of pneumocystis carinii contamination. An infection with Pneumocystis carinii deteriorates the clinical course of ARDS. Effective drugs were the combination of trimethoprim and sulfamethoxazole. Under this therapy we always saw a decrease of infiltrations in the chest-x-ray as well as an improved gas exchange. No relapse was seen in any case. PMID- 1873410 TI - [Physical characteristics of devices for artificial respiration]. AB - Expired air resuscitation forms an essential part of First Aid in patients with respiratory insufficiency. The use of devices should encourage the rescuer to start the measure, make it easier to perform and protect him from a possible transmission of infectious material. 17 devices (mask, tube instruments) were examined in respect of their physical properties (resistance, leakage). None of them fulfilled all the criteria relevant for their use. In most of them changes and modifications seem to be necessary. Mask and tube instruments have definitive disadvantages compared to foil-like adjuncts which are being developed at present. PMID- 1873411 TI - [Safe intra-clinic transport of intensive-care patients. A concept that avoids monitoring and treatment gaps]. AB - We describe a transport concept ensuring unlimited continuation of cardiocirculatory monitoring, drug therapy and artificial ventilation during transfer of critically ill patients within the hospital. The basis of this concept is a mobile transport unit which can be hooked to the patient's bed, containing a power pack for the monitor, respirator or other devices dependent on power supply. The concept probably improves safety of patients not only during postoperative transfer of the ICU but enables also the safe transfer of critically ill patients from the ICU to diagnostic or therapeutic procedures. PMID- 1873413 TI - [The standby function--an unloved child of anesthesia?]. PMID- 1873412 TI - [Complete airway obstruction by a prosthesis powder. The problem of protecting the airway in emergency service]. AB - An extraordinary occurrence of death is reported due to blocking of the entrance of the larynx by a denture adhesive. The improper usage of this material by a mentally disturbed woman of 66 years of age caused her death by suffocation. In such a case an intubation can involve a transfer of the viscous material to the larynx. Therefore a coniotomy or a tracheotomy should be performed. PMID- 1873414 TI - [Ways of economizing on homologous blood. Concepts of autologous blood transfusion]. AB - Transfusion of homologous blood may be associated with various complications. In this review, the authors present concepts of prevention of homologous blood transfusion. Different autotransfusion techniques are discussed, i.e., predeposit of autologous blood, plasmapheresis, normovolaemic haemodilution, blood salvage with/without cell washing, postoperative blood salvage of drainage blood, anaesthesia and surgical techniques as well as drugs for minimizing blood loss. The third part of the essay deals with indications of each technique depending on the surgical field. The authors conclude with unanswered questions and problems of the future. PMID- 1873415 TI - [Intranasal premedication of young children using midazolam (Dormicum). Clinical experience]. AB - The effect of 0.2 mg/kg body weight intranasal midazolam as a premedicant was investigated in 38 children (age 2-13 years, body weight 10-28 kg) prior to ENT surgery. Intranasal midazolam showed a rapid onset of action with 79% and 95% of the children being sufficiently premedicated at 5 minutes (p less than 0.05) and 10 minutes (p less than 0.01) after application, respectively, as opposed to 45% prior to this. This finding is in keeping with pharmacokinetics showing a tmax of intranasal midazolam of 11 minutes and a bioavailability of 51% in children (10). With the advent of a higher concentrated solution of midazolam intranasal application is also conceivable as a premedication in adults. PMID- 1873416 TI - [Intra- and postoperative autotransfusion in hip joint surgery. Effectiveness, bacteriology]. AB - The efficiency of intraoperative and postoperative autotransfusion with a cell separator, the elimination of a cephalosporin administered for prophylaxis of infection and bacterial contamination of the blood retransfused were studied in 56 patients undergoing hip arthroplasty (n = 33) or exchange reoperation of hip arthroplasty (n = 23). Intraoperatively only a limited amount of the lost erythrocytes could be retransfused: in hip arthroplasty 250 ml (median) packed red cells of 700 ml blood loss, in exchange reoperation 750 ml of 2200 ml. Postoperative autotransfusion was more effective: during the autotransfusion period (until 6 h after the beginning of the operation) 375 ml of 650 ml and 500 ml of 830 ml could be retransfused in the two groups. Cefuroxime was eliminated effectively from the autologous blood by the cell washing process, usually below the limit of detection. In the washed autologous red blood cells of 3 patients (= 5.4%) bacterial contamination could be demonstrated in low titres (less than or equal to 10/ml). No clinical signs of bacteremia were observed during retransfusion. Postoperative autotransfusion contributes considerably to the total amount of autologous erythrocytes retransfused. Bacterial contamination of the processed autologous blood is infrequent and probably without clinical significance. PMID- 1873417 TI - [Perioperative treatment of a patient with myotonic muscular dystrophy (Curschmann-Steinert disease)]. AB - The perioperative period is hazardous for patients with neuromuscular disorder. In case of dystrophia myotonica the anaesthesist must avoid all stimuli that may cause a myotonic crisis. If neuromuscular blockade is required, the moderately long-acting vecuronium bromide seems to be the drug of first choice. Blockade and recovery should be monitored. Postoperative pulmonary complications can be minimised by using regional anaesthetic techniques including epidural anaesthesia with local anaesthetics and/or opioids. PMID- 1873418 TI - [The effect of halothane anesthesia on pulmonary circulation regulation during unilateral hypoxic ventilation]. AB - Controversies exist over the influence of inhalation anaesthesia on blood flow regulation in response to local alveolar hypoxia. This study investigates the blood flow diversion from a hypoxic to an oxygenated lung in anaesthetized and ventilated animals in comparison to unanaesthetized animals. Chronically instrumented adult ewes (n = 14, 32-45 kg) were intubated one week after surgery with a modified Carlen's tube, allowing separate ventilation of the left and right lung. In the awake state (n = 7) or after one hour of constant anaesthetic conditions (n = 7, halothane 1.6% and 2.4%), cardiac output (thermodilution) and left pulmonary blood flow (ultrasonic transit time) were evaluated. Then, under identical ventilatory conditions, the left or right lung, alternately, was rendered hypoxic for 10 min by ventilation with nitrogen. The contralateral lung was ventilated with oxygen. After 10 min, haemodynamics were again recorded. The changes in left pulmonary blood flow under unilateral lung hypoxia were similar either in the awake or the anaesthetized state. Thus, we conclude that, under these experimental conditions, halothane anaesthesia and mechanical ventilation have no influence on blood flow regulation under unilateral lung hypoxia. PMID- 1873420 TI - [Cerebroprotection--catchword or therapeutic concept?]. PMID- 1873419 TI - [Fatty emulsions in parenteral feeding following liver transplantation. A study of the neurotropic effect of MCT/LCT emulsions using EEG]. AB - In the early postoperative period after liver transplantation a possible neurotropic side effect of middle-chain triglycerides used for total parenteral nutrition (TPN) was evaluated by EEG and Glasgow Coma Scale. Group I: no fat for TPN; Group II: 0.7 g/kg body weight (BW) and day, of MCT/LCT emulsion; Group III: 1.5 g/kg BW and day, of MCT/LCT emulsion. Only on postoperative day 5/6 significant differences in distribution of background activity in the EEG were seen between Group I and II. Patients in Group I showed more pathological EEG patterns (Mann-Whitney-U-test p less than 0.05). Per discriminant analysis an influence of applicated fatty acids on the registered background activity could be excluded. Instead an underlying rejection of the graft in 7 of 10 patients could be made responsible for deterioration of the EEG pattern. Following the presented data a negative neurotropic effect of MCT/LCT emulsions in the described dosages can be negated. PMID- 1873421 TI - [The current status of cerebral resuscitation]. PMID- 1873422 TI - [Thiopental concentrations in the whole blood of pregnant and non-pregnant patients in the first minutes following injection. Forensic aspects]. AB - Thiopentone concentrations in blood following injection of the induction solution (Thiopental, 2.5%) may be critical in the context of lethal complications arising during induction of anaesthesia and thereby the toxicological aspects of this drug can become an issue in forensic considerations. The study was designed to find out whether the dose of injected thiopentone may be calculated from blood levels measured in nine pregnant and ten non-pregnant patients. The doses injected ranged from 4-5 mg per kg body weight. The drug was administered as a single bolus dose to the patients undergoing Caesarean section. In the non pregnant group the first dose of thiopentone was given over 25 s. After that repeated doses of 50 mg were injected over 2s every 20s until the eyelid reflex was ceased. Blood samples for determination of thiopentone were withdrawn from an indwelling catheter inserted to a large cubital vein in the arm opposite that used for the injection and thiopentone levels were measured from blood after column extraction (Extrelut) using spectrophotometry. Venous peak values were found 40-115s after injection in the Caesarean group (mean: 20.3 micrograms kg-1) and were higher than in the non-pregnant patients (97-190s, mean: 17.8 micrograms kg-1). No correlation was found regarding venous peak levels (mgkg-1 blood) and induction dose (mgkg-1 body weight), neither in the pregnant nor in the non pregnant group. Our findings would suggest that the injected thiopentone dose cannot be calculated from the concentration of the drug in the blood. Forensic conclusions concerning the onset of lethal complications during the induction of anaesthesia cannot be drawn on the grounds of venous thiopentone concentrations. PMID- 1873423 TI - [Changes in affect in the postoperative phase: droperidol versus dipotassium chlorazepate]. AB - Various studies showed an increase of anxiety and agitation after premedication with thalamonal. Subject of the present study was to specify if the psychotropic effect of the neuroleptic drug dehydrobenzperidol given during surgery is also evident during the postoperative period. Patients undergoing tympanoplastic surgery under general anaesthesia were examined by means of a psychometric analogous self judgement scale seven hours following surgical intervention. Sleep behaviour during the first postoperative night was evaluated via a question sheet. The results show that changes in condition, known from the thalamonal discussion, e.g. increase of agitation, irritability, anxious depression -- also occur during the postoperative period. During the first postoperative night, sleep was greatly disturbed. The results of a comparison group who received the benzodiazepine dipotassium clorazepate instead of dehydrobenzperidol showed a better postoperative condition and sleep behaviour. PMID- 1873424 TI - [Analgesia using oral administration of tilidine naloxone for extracorporeal shockwave lithotripsy. A double blind study]. AB - Reduction in pain perception during ESWL due to a technical modification of the lithotriptor was expected and prompted a reassessment of anaesthesia techniques for ESWL. In this study the need for analgesic treatment had to be investigated. After satisfactory preliminary results in a previous pilot study, the value of the oral combination of the anti-anxiety drug dipotassium clorazepate on the evening before ESWL together with the analgesic tilidine-naloxone before treatment was tested in a randomised double-blind study in 120 patients. In case of intolerable pain during the treatment all patients were free to ask for additional intravenous analgesic medication (fentanyl). During ESWL, 28.3% of the tilidine-N group patients and 6.7% of the placebo group were pain-free, whereas intolerable pain was reported by 30% of the tilidine-N group and 56.7% of the placebo group. Therefore, 70% of the tilidine-N group patients were treated without any additional analgesic or sedative medication. The good experience with this oral anaesthesia approach, the lack of significant side effects and a good acceptance by the patients warrant further recommendation of this technique. PMID- 1873425 TI - [Successful treatment of the neuroleptic malignant syndrome using i.v. dantrolene sodium in the neurologic intensive care station]. AB - The neuroleptic malignant syndrome (NMS) is one of the most dramatic psychiatric disorders every doctor in intensive care medicine can be confronted with. Two cases of successful treatment of NMS with intravenous application of dantrolene are presented. Although we used two very different doses, the treatment results were the same. Further studies will therefore be necessary to assess the optimal doses for this therapy. PMID- 1873426 TI - [An electrolyte-adapted heparin solution for the determination of blood gases and electrolytes in whole blood]. AB - Blood gases, pH, sodium, potassium, chloride, and ionised calcium in whole blood samples can be determined simultaneously in modern instruments. Preparing syringes with conventional heparin solutions causes a relevant bias of the electrolyte concentrations (especially K+ and Ca2+) by dilution of the sample. Additionally, ionised calcium is decreased by binding to heparin. The solution described in the present paper yields a final heparin concentration of 4-6 mU/l, thus eliminating the calcium binding effect. The dilution effects are antagonised by an electrolyte composition that is similar to normal plasma. The heparin solution is commercially available. PMID- 1873427 TI - [Determinations by indirect calorimetry need not be expensive and technically complicated. A new measurement system and its validation]. AB - Presentation of a newly conceived measuring instrument to determine the energy expenditure of critically ill patients at the bedside by means of indirect calorimetry. The special advantages of the measuring instruments are easy handling, little maintenance and very low working expenses and prime costs. The accuracy of measurement is considerable nd is comparable with that of other measuring methods, as has been established by an extensive validation. PMID- 1873428 TI - [Accidental diazepam overdose in a 12-month-old infant. Therapy using flumazenil]. PMID- 1873429 TI - Dietary patterns of female nonsmokers with and without exposure to environmental tobacco smoke. AB - The relationship of passive smoking to diet was examined in 82 female nonsmokers who provided a quantitative diet history in 1986. Exposure to environmental tobacco smoke (ETS) was assessed by urinary cotinine measurement. Mean values for each dietary variable, adjusted for age, ethnicity, education, and last week's ethanol intake, were compared among unexposed women and women with low or high ETS exposure. Linear relationships with amount of ETS exposure were also sought. Intakes of beta-carotene and cholesterol were found to be inversely related to ETS exposure. Since these nutrients have been associated with lung cancer risk, they are potential confounders of the passive-smoking/lung-cancer relationship. Although we estimate the confounding effect of these dietary factors to be modest, they should be measured carefully in future studies of this relationship. PMID- 1873430 TI - Diet and the risk of in situ cervical cancer among white women in the United States. AB - A case-control study of women with incident in situ and invasive cervical cancer was conducted during 1982-83 in five US areas reporting to the Comprehensive Cancer Patient Data System: Birmingham, AL; Chicago, IL; Denver, CO; Miami, FL; and Philadelphia, PA. Controls were selected by random-digit dialing and matched to invasive cases on age, race, and telephone exchange. Of the white non-Hispanic in situ cases and controls identified, 229 (78 percent) and 502 (74 percent) were successfully interviewed. Diet was assessed by asking about the usual adult frequency of consumption of 75 food items and the use of vitamin supplements. Included were the major sources of the four micronutrients postulated to reduce the risk of cervical cancer: carotenoids, vitamin A, vitamin C, and folate. Weak inverse associations between risk of in situ disease and intake of carotenoids, vitamin C, folate, fruit, and vegetables/fruits were noted but, with further analysis, these seemed attributable to residual confounding by the multiple lifestyle-related risk factors for this disease and possibly to selection bias. Vitamin A and vegetable intake were unrelated to risk. Dark yellow-orange vegetable consumption and duration of multivitamin use were each strongly related to reduced risk of in situ disease (P for trend = 0.02 and 0.002, respectively) and need to be evaluated in other studies. The absence of persuasive protective effects for the four micronutrients and the similar findings from our analysis of invasive cervical cancer do not concur with other epidemiologic studies and suggest that the role of diet and nutrition in the etiology of cervical cancer is not yet resolved. PMID- 1873431 TI - Tobacco, alcohol, and diet in the etiology of laryngeal cancer: a population based case-control study. AB - Cancer of the larynx constitutes an increasingly important problem in Polish males during the last 25 years. A population-based case-control study of laryngeal cancer among people under 65 years of age was conducted in Lower Silesia, a province in Southwest Poland, from 1986 to 1987, with 249 newly diagnosed cancer cases and 965 controls. The estimated relative risk (RR) for smoking and alcohol are both very high: for smoking more than 30 cigarettes, RR = 59.7 (95 percent confidence interval [CI]: 13.0-274); for drinking vodka regularly for more than 30 years, RR = 10.4 (95 percent CI: 4.0-27.2). Exposures to alcohol and tobacco show a clear multiplicative effect in all categories of exposure. The risk was shown to be reduced by quitting smoking (RR = 0.3, 95 percent CI: 0.14-0.64, after 10 years) or by having a history of intermittent smoking. Poor nutrition was also identified as a strong independent risk factor. However, data quality regarding this factor is not as high as for tobacco and alcohol. Smoking alone accounts in this study for an estimated 95.2 percent of all the cases of laryngeal cancer. PMID- 1873432 TI - Parental age at birth and risk of breast cancer in daughters: a prospective study among US women. AB - We examined the relation between parental age at birth and risk of breast cancer among daughters in a population of 118,309 US women who were 30 to 55 years of age in 1976 and without prior diagnosis of cancer. During 1,140,239 person-years of follow-up, we documented 1,799 incident cases of breast cancer in this population. After adjusting for established breast cancer risk factors, we observed only a weak and nonsignificant trend in risk of breast cancer with increasing maternal age at birth and no relation for paternal age. After adjusting for other risk factors, the chi trend was 1.10, P = 0.27 for increasing maternal age at birth. Daughters born to mothers 30 to 34 years of age had an age adjusted relative risk of breast cancer of 1.11 (95% confidence interval: 0.89, 1.37) compared to daughters born to mothers less than 20 years of age. The weak positive trend in risk with increasing maternal age was present among both pre- and postmenopausal women. These findings suggest that there is little or no association between maternal age and risk of breast cancer, and that paternal age is not related to risk of breast cancer. PMID- 1873434 TI - Dietary fat and cancer: rejoinder and discussion of research strategies. PMID- 1873435 TI - Vasectomy and the risk of prostate cancer in a cohort of multiphasic health checkup examinees: second report. AB - The relationship of vasectomy to prostate cancer was studied in 5,119 men men with a self-reported history of vasectomy, identified at multiphasic health checkups undergone during 1977-82 while members of the Northern California Kaiser Permanente Medical Care Program. Three unvasectomized comparison subjects were identified for each vasectomized man, matched for age, race, marital status, and date and location of the examination. Follow-up for incident prostate cancer was conducted for a mean length of 6.8 years. The relative risk of prostate cancer associated with vasectomy was 1.0 (95% confidence interval = 0.7 - 1.6); the relative risk was approximately one, regardless of length of interval (less than 10 years, 10-20 years, more than 20 years) between vasectomy and multiphasic health checkup or the age at vasectomy (less than 40 years vs more than 40 years). These data support earlier findings reported in this study group of the lack of an association of vasectomy with subsequent risk of prostate cancer. PMID- 1873433 TI - The epidemiology of HTLV-I infection. AB - It has been 10 years since the discovery of the human T-cell lymphotropic virus type I (HTLV-I), the first human retrovirus. During the past decade, significant progress has been made in understanding the transmission of the virus and defining its geographic distribution. It has been shown conclusively that HTLV-I is a causal factor in the induction of both adult T-cell leukemia/lymphoma and HTLV-I-associated myelopathy. However, the pathogenesis of each of these conditions is not clear, and in the light of the evidence of immune dysfunction seen among carriers of the infection, it is likely that other associated diseases will be identified. The challenge in the next decade will be to develop and implement therapeutic interventions among carriers to prevent such diseases as well as to curtail transmission within endemic populations. PMID- 1873437 TI - Cancer in Italian migrants. AB - Migration of Italians to other parts of the world has a long history and has involved very large numbers of individuals. The study of the health consequences of this migration is made possible by the availability of statistics on mortality and morbidity, both in Italy and in the host countries, and of social and economic information on the various Italian communities abroad. The results of the major studies are reviewed, comparing the rates in immigrants with those in the host countries and in Italy. The differences in cancer rates between Italian and local-born populations--for stomach cancer in both sexes, and for cancer of the colon, lung, and breast in females, and for prostate cancer--are consistent with the direction of differences between rates in Italy and those in the host countries. For colon and rectum cancer in males, there are unexpected findings in most of the United States' studies. Analysis by duration of residence shows changes in the risk for several sites in males, but not in females, according to length of stay in the host country. This finding possibly reflects greater stability of habits and lifestyle in females compared to males. PMID- 1873436 TI - A prospective study of body mass, height, and smoking on the risk of colorectal cancer in women. AB - Female registered nurses in the United States who responded to a questionnaire in 1976 that inquired about height, weight, and smoking history were followed for the development of colon or rectal cancers through May of 1984. Among the 118,404 respondents free of cancer in 1976, 191 colon cancers and 49 rectal cancers were observed during 916,170 person-years of follow-up. After omitting cases diagnosed within two years of weight report, we found little overall relation of body mass (Quetelet's) index to colon cancer risk; however there was a suggestion of elevated risk for the heaviest category of body mass index (greater than or equal to 29 kg/m2, relative risk (RR) = 1.5; 95 percent confidence interval = 0.8 - 2.7) relative to the lowest category (less than 21 kg/m2). Self-reported body mass index from adolescence had a slightly more pronounced, although not significant, association with risk of colon cancer. Increasing height was significantly associated with colon cancer (RR = 1.6, 95 percent confidence interval = 1.1 - 2.5 for the tallest category [greater than or equal to 168 cm] versus the shortest (less than 160 cm], trend, P = 0.04). Measures of current or past smoking failed to demonstrate any consistent relationship with colon cancer. PMID- 1873438 TI - The increasing incidence of breast cancer since 1982: relevance of early detection. AB - Breast cancer incidence in the United States has been rising dramatically since 1982, as shown in data collected by the Surveillance, Epidemiology, and End Results (SEER) Program. In women aged 50 and older, incidence rates for in situ and localized invasive tumors have increased over the period 1982-86, while rates for regional and distant tumors have remained stable. The incidence of localized tumors less than 1.0 cm, 1.0-1.9 cm, and 2.0-2.9 cm in size has increased more rapidly than that of tumors 3.0 cm or more in size among women over age 50. Survival rates also have improved among cases diagnosed over this time period. These data suggest that early detection may be playing a role in the recent increase in female breast cancer incidence, though other factors cannot be ruled out. Conclusions regarding improved cancer control await confirmation by reduced breast cancer mortality. PMID- 1873439 TI - Follow-up of asymptomatic HTLV-I carriers among blood donors in Kyushu, Japan. AB - We examined mortality from adult T-cell leukemia/lymphoma (ATL/ATLL) and other diseases alleged to be associated with human T-lymphotropic virus type I (HTLV-I) among anti-HTLV-I antibody-positive blood donors in Kyushu, Japan. During 1984 87, a total of 3,991 blood donors aged 40 years or over were followed from the date of donation to the date of death or the end of the study. Crude mortality rates from ATL (with 95 percent confidence intervals) were 68 per 100,000 (13 202) for males and 36 per 100,000 (3-132) for females. The rates were underestimated by approximately 50 percent because of self-selection and short observation periods. Neither death rates from other cancers nor death rates from all cancers were elevated. PMID- 1873440 TI - The relationship between animal fat intake, cigarette smoking, and lung cancer. AB - An international ecologic study on the relationship between fat intake, cigarette consumption, and age-specific lung cancer mortality rates was conducted using data obtained from 29 countries. The 1969-71 and 1984-86 mortality rates for lung cancer were related to smoking habits and to levels of animal fat intake. Highly significant independent positive correlations for lung cancer with both cigarette smoking and animal fat consumption were seen. No significant independent relationship was found between lung cancer mortality and vegetable fat consumption. In a multiple regression analysis linking lung cancer mortality to dietary intake of animal fat, cigarette smoking, and the interaction term between cigarette smoking and animal fat intake, only the latter term was significant (P less than 0.001) pointing towards a role for animal fat as a promoter of lung cancer. PMID- 1873442 TI - Birth order and breast cancer risk. AB - It has been hypothesized that prenatal exposure to maternal estrogens may be a risk factor for breast cancer in the offspring. In two recent studies, maternal estradiol levels in the first pregnancy have been compared to those in the second, and in both studies levels were higher in the first pregnancy. If both the hypothesis and the reported findings were true, women born as their mother's second child would be expected to have lower risk for breast cancer than first born women. Data from 1,468 cases of breast cancer and 4,175 hospital controls from three previously published studies were modelled through multiple logistic regression to evaluate this possibility. The size of the woman's sibship was not related to breast cancer risk. On the other hand, second-born women had, as predicted, lower breast cancer risk than first-born women, although the difference was nominally significant only among premenopausal women. The relative risk for breast cancer, contrasting second-born to first-born women, and the corresponding 95 per cent confidence intervals, were 0.71 (0.54-0.94) among premenopausal women, 0.94 (0.76-1.17) among postmenopausal women, and 0.86 (0.73 1.02) among all women, controlling for menopausal status. PMID- 1873441 TI - Adult dietary intake and prostate cancer risk in Utah: a case-control study with special emphasis on aggressive tumors. AB - A population-based case-control study in Utah of 358 cases diagnosed with prostate cancer between 1984 and 1985, and 679 controls categorically matched by age and county of residence, were interviewed to investigate the association between dietary intake of energy (kcal), fat, protein, vitamin A, beta-carotene, vitamin C, zinc, cadmium, selenium, and prostate cancer. Dietary data were ascertained using a quantitative food-frequency questionnaire. Data were analyzed separately by age (45-67, 68-74) and by tumor aggressiveness. The most significant associations were seen for older males and aggressive tumors. Dietary fat was the strongest risk factor for these males, with an odds ratio (OR) of 2.9 (95 percent confidence interval [CI] 1.0-8.4) for total fat; OR = 2.2 (CI = 0.7 6.6) for saturated fat; OR = 3.6 (CI = 1.3-9.7) for monounsaturated fat; and OR = 2.7 (CI = 1.1-6.8) for polyunsaturated fat. Protein and carbohydrates had positive but nonsignificant associations. Energy intake had an OR of 2.5 (CI = 1.0-6.5). In these older men, no effects were seen for dietary cholesterol, body mass, or physical activity. There was little association between prostate cancer and dietary intake of zinc, cadmium, selenium, vitamin C, and beta-carotene. Total vitamin A had a slight positive association with all prostate cancer (OR = 1.6, CI = 0.9-2.4), but not with aggressive tumors. No associations were found in younger males, with the exception of physical activity which showed active males to be at an increased but nonsignificant risk for aggressive tumors (OR = 2.0, CI = 0.8-5.2) and beta-carotene which showed a nonsignificant protective effect (OR = 0.6, CI = 0.3-1.6). The findings suggest that dietary intake, especially fats, may increase risk of aggressive prostate tumors in older males. PMID- 1873443 TI - Oral contraceptives and the risk of endometrial cancer. AB - The relationship between the use of combination oral contraceptives (OCs) and the risk of endometrial cancer was assessed in a case-control study conducted in the Swiss Canton of Vaud between 1 January 1988 and 31 July 1990. Subjects included 122 women aged 75 or less with histologically confirmed endometrial cancer, and 309 control women in hospital for acute conditions unrelated to OC use. Overall, 14 percent of cases and 27 percent of controls had ever used OCs, corresponding to a multivariate relative risk (RR) of 0.5 (95 percent confidence interval [CI]: 0.3, 0.8). The risk of endometrial cancer was found to be related inversely to duration of OC use: RR = 1.0 for less than two years of OC use; 0.5 for two to five years; and 0.3 (95 percent CI: 0.1, 0.7) for more than five years. The protection appeared greater within 20 years since last use, and the RR rose to 0.8 after 20 or more years since last use; numbers are too small, however, for reliable inference from these subanalyses. No significant interaction or modifying effect was observed with other major factors related to endometrial cancer, including parity, body mass index, estrogen replacement therapy, and cigarette smoking. While this study provides further evidence for the protective effect of OCs against risk of endometrial cancer, the relationship requires continued evaluation to assess the long-term implications and public health impact of OC use. PMID- 1873444 TI - Evaluation of cancer prevention strategies by computerized simulation model: an approach to lung cancer. AB - A computerized simulation model was developed to evaluate the potential impact of primary and secondary prevention on lung cancer mortality in Japan. The natural history of lung cancer was modeled as a Markovian stochastic process from cancer free to preclinical, clinical, and finally to terminal states. The increase in mortality rate of lung cancer among males aged 75 to 79 years has been the major force of increase in the total number of lung cancer deaths in Japan. The simulation showed that this tendency would continue until the late 1990s, presumably due to the increase in the proportion of ever-smokers in that cohort, who started smoking at an earlier age than did prior generations. It was shown that the number of lung cancer deaths can be reduced either by smoking cessation or screening programs, and that the reduction is proportional to the increase in the annual smoking-cessation rate and to the annual increment in the screening rate. However, only two to three percent reduction of lung cancer deaths in the year 2001 can be expected when the annual smoking-cessation rate is raised from the current value of 0.46 percent to five percent during the period from 1991 to 2000 or when the screening rate is increased by three percent annually for the same period. PMID- 1873445 TI - Non-occupational risk factors for adult soft-tissue sarcoma in northern Italy. AB - The role of socioeconomic and anthropometric indicators, tobacco, alcohol consumption, dietary habits, and medical history in the etiology of soft-tissue sarcoma (STS) was examined in a hospital-based case-control study, conducted in the Friuli-Venezia Giulia region of northeast Italy, between 1985 and 1990. A total of 88 STS cases (53 males and 35 females; median age: 52 years) and of 610 controls (306 males and 304 females; median age: 54 years) were interviewed. There were significant excess risks associated with a history of herpes zoster infection (odds ratio [OR] = 2.4, 95 percent confidence interval [CI] = 1.1-5.3), chicken pox (OR = 2.2, CI = 1.2-4.3) and mumps in childhood (OR = 2.0, CI = 1.1 3.9). History of diabetes was also linked to a nonsignificant increase in STS risk (OR = 1.8, CI = 0.6-5.4), whereas exposure to radiation for diagnostic or therapeutic purposes was not related to the probability of developing STS. None of the investigated socioeconomic and anthropometric indicators seemed to affect STS risk; neither did tobacco smoking, nor consumption of alcohol, coffee, and tea beverages. Conversely, among the dietary habits investigated, a significant positive association emerged with an increasing frequency of consumption of dairy products (chi 2 for trend = 6.8, P less than 0.01) and oil (chi 2 for trend = 4.3, P less than 0.05), while a negative association was seen for intake of whole grain bread and pasta (OR for highest cf lowest tertile = 0.4, CI = 0.2-0.9). PMID- 1873446 TI - Urinary salt excretion and stomach cancer mortality among four Japanese populations. AB - A relationship between salt intake and the occurrence of stomach cancer has been suggested by both epidemiologic and experimental data. To test this hypothesis, urinary excretion of salt in 24 hours and dietary intake of salt were measured in four male populations with different levels of stomach cancer mortality. Age adjusted mortality rate of stomach cancer showed a high correlation (r2 = 0.995) with the average amount of salt excretion in 24-hour urine. This strong correlation, however, was not shown (r2 = 0.265) with dietary salt intake calculated from the standard food-composition table. The results confirmed the important role of salt in the development of stomach cancer in Japan, and raised the problem of evaluating the level of salt intake by using the uniform composition table. PMID- 1873447 TI - Risk factors for stomach cancer: a population-based case-control study in Shanghai. AB - A population-based case-control study of stomach cancer was conducted among the teachers and staff of primary and middle schools in Shanghai. A total of 84 cases of stomach cancer were identified in all schools and 2,676 controls were drawn from the teachers and staff of a randomly selected sample of 40 primary and 15 middle schools. Data were analyzed by a multivariate logistic regression model. The analysis indicated that a positive family history of stomach cancer, cigarette smoking, low consumption of fruits, and low consumption of strong tea were significantly associated with stomach cancer incidence. PMID- 1873448 TI - Feasibility of conducting a lung-cancer chemoprevention trial among tin miners in Yunnan, P. R. China. AB - Tin miners in Yunnan Province in southern China have an extremely high rate of lung cancer, more than one percent per year among those at 'high risk' (40+ years old, with 10+ years of underground mining and/or smelting experience). The extraordinary lung cancer rates result from combined exposure to radon, arsenic, and tobacco smoking (cigarettes and/or bamboo water pipe). A study to determine the feasibility of conducting a large-scale, lung-cancer chemoprevention trial was conducted in 1986 among currently employed or retired miners from the Yunnan Tin Corporation in the city of Gejiu. The study was designed to answer four questions: (i) Could potentially eligible miners be identified and recruited? (ii) Could intervention agents be shipped successfully from the United States to the study area and be appropriately distributed? (iii) Would miners adequately adhere to the study protocol and comply with the intervention regimen? (iv) Could potential adverse effects be monitored and documented? The six-month feasibility study yielded affirmative answers to each of these questions. A roster of over 7,000 high-risk miners was compiled. Four agents (vitamin A, 25,000 IU; beta carotene, 50 mg; vitamin E, 800 IU; and selenium, 400 micrograms) were administered daily with placebos to 350 miners according to a 2(4) factorial design. Adherence, assessed by pill counts and serum micronutrient levels, was approximately 90 percent. The findings from this preliminary study indicate that a full-scale, lung-cancer chemoprevention trial in this population is feasible. PMID- 1873449 TI - Reproductive factors and colorectal cancer. AB - Descriptive and analytical epidemiology have suggested that cancer of the colorectum may have reproductive correlates similar to those of breast cancer (e.g., protection by parity and early age at first birth), but the evidence is still controversial. We therefore reviewed published data from 15 case-control investigations, two cohort studies, and one cancer registry-based study from seven different countries. With reference to parity, statistically significant protection for colorectal cancer was found in three case-control studies; in four other studies, significant inverse relationships of parity were observed with colon cancer, but not with rectal cancer. Among the remaining 12 studies, relative risks below unity for parous or multiparous women were observed in four. There was no appreciable trend in risk in four others; in two, there was nonsignificant increased risk with parity; and in one, a significant increased risk. Information on age at first birth was available from 12 studies. Three reported significant trends of increased risk with increasing age at first birth- one found a direct association of borderline significance; six indicated no evidence of association; and two reported an inverse trend in risk of borderline significance. Findings on age at menarche were inconsistent and mostly negative, although an inverse significant association was reported, especially regarding colon cancer, in one investigation. In all the six studies, which provided information on age at menopause, there was a hint of protection, although nonsignificant, for women who underwent natural menopause at an older age. Two studies reported a direct association of colorectal cancer with use of oral contraceptives, and another showed an inverse relationship with the use of menopausal estrogens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873450 TI - Radon daughter exposures at the Radium Hill uranium mine and lung cancer rates among former workers, 1952-87. AB - The aim of this historical (retrospective) cohort study was to investigate the relation between occupational exposure to radon daughters and subsequent mortality from lung cancer. Participants were former workers from the Radium Hill uranium mine, which operated in eastern South Australia from 1952 to 1961. A total of 2,574 workers were identified from mine records. Exposures to radon daughters were estimated from historical records of radon gas concentrations in the mine and from individual job histories. Exposures of underground workers were low by comparison with other mines of that period (mean 7.0 Working Level Months [WLM], median 3.0 WLM). Thirty-six percent of the cohort could not be traced beyond the end of employment at Radium Hill. Among those traced to the end of 1987, lung cancer mortality was increased relative to the Australian national population of the period (Standardized Mortality Ratio = 194, 95 percent confidence interval [CI] = 142-245). Compared with surface workers, lung cancer mortality was markedly increased in the underground workers with radon daughter exposures greater than 40 WLM (relative risk = 5.2, CI = 1.8-15.1). From the available information, we conclude that this increase is unlikely to be due to differences in smoking habits or other confounders. Taken together with the findings from other occupational studies, these results support current moves towards more stringent radiation control in the workplace, and underline the importance of research into the possible effects of domestic radon exposures. PMID- 1873451 TI - Age at menarche and estrogen concentrations of adult women. AB - It has recently been reported that women with a recorded early menarche had approximately two-fold greater follicular phase serum E2 (estradiol) levels than women with menarche at age 13 or later. We have evaluated E1 (estrone) and E2 concentrations in the blood, and estrogen concentrations in the urine, in two groups of premenopausal women (mean ages 33 and 38 years) for categories of age at menarche. Study subjects were 106 Caucasian women in the United States (assessed for E1, E2, and urinary estrogens) and 39 women from Shanghai, China (assessed for E2). US subjects were classified according to whether their recalled menarche occurred before age 12, at age 12, or at age 13 or older. The mean age at recalled menarche of the Shanghai subjects was considerably older, and their ages at menarche were classified as less than age 15, age 15, and age 16 or older. We found little evidence in these premenopausal women in their thirties of an effect of age at menarche on estrogen levels. A large-scale study of women in the age range 20-40 years is necessary to investigate this important issue more thoroughly. PMID- 1873452 TI - Dietary risk factors in intestinal and diffuse types of stomach cancer: a multicenter case-control study in Poland. AB - A hospital-based, multicenter, case-control study has been performed in Poland covering 741 incident stomach-cancer cases (520 males and 221 females) and the same number of controls. All stomach-cancer diagnoses were evaluated for histologic type according to the Lauren criteria. Fifty-one percent were of the intestinal type, 35 percent of the diffuse type, and 8.5 percent of the mixed type. The frequency of consumption of individual food items and several food groups was analyzed and the association of various foods with stomach cancer risk was evaluated after controlling for sex, age, occupation, education, and residency. Increased consumption of sausages was related significantly to gastric cancer risk, whereas increased consumption of cheese products, nonwhite bread, vegetables, and fruit was associated with decreased risk. A particularly strong decrease in risk was associated with consumption of radishes and onions. When consumption of fruits and vegetables, sausages, nonwhite bread, and cheese were introduced simultaneously in a multivariate model, independent effects were found only for fruit and vegetables, sausages, and nonwhite bread. The use of table salt, the frequency of eating hot meals, and an irregular eating pattern were also associated with increased risk, while additional consumption of fruit between meals showed reduced risk. If a reduction in vegetable and fruit consumption took place after marriage, an increased risk for stomach cancer was found, whereas augmented consumption of these food items after marriage decreased the risk. Separate risk models were calculated for stomach cancer of the intestinal and diffuse types, but both histologic varieties showed the same pattern of associations with dietary risk factors. PMID- 1873453 TI - Education and breast cancer mortality: experience from a large Norwegian cohort study. AB - Socioeconomic status has been regarded as an established risk factor for breast cancer. We have studied the association between socioeconomic status, operationalized as years of completed schooling, and breast cancer mortality in a Norwegian cohort. A total of 425,884 currently married women, aged 35-54 years at the Norwegian Census in 1970, was followed through 1985. No relation was found between level of education and breast cancer mortality. PMID- 1873454 TI - A randomized trial of smoking cessation interventions in general practice in Italy. AB - The purpose of this study was to examine the effectiveness of different practice based approaches to assist patients of primary care physicians to quit smoking and sustain cessation. Forty-four nonsmoking general practitioners volunteered for the study. After a period of training, they randomized 923 smoking clients, unselected for motivation toward quitting, to four different intervention groups: (i) minimal intervention, consisting of one single counselling session and a brief handout on quitting techniques; (ii) repeated counselling including reinforcing sessions at Months 1, 3, 6, and 9; (iii) repeated counselling and use of nicotine gum; and (iv) repeated counselling and spirometry. Biochemically validated smoking status was assessed at six and 12 months after recruitment. The proportion of verified quitters at 12 months was 4.8 percent among subjects randomized to the minimal intervention group, compared to 5.5 percent, 7.5 percent, and 6.5 percent among those randomized to the three repeated-counselling groups. In no treatment group was the outcome significantly different from that for one-time counselling at the (P less than 0.05) level. Lack of power, contamination, and low attendance at reinforcing sessions should be taken into account in interpreting the results. PMID- 1873455 TI - Alcohol consumption and breast cancer risk in Denmark. AB - The influence of alcohol consumption on breast cancer risk was evaluated in a population-based case-control study, including 1,486 cases diagnosed over a one year (1983-84) period in Denmark. Cases were identified from the files of the nationwide clinical trial of the Danish Breast Cancer Cooperative Group and the Danish Cancer Registry. The control group was an age-stratified random sample of 1,336 women from the general population. Data on risk factors were collected by self-administered questionnaires. The association of alcohol consumption with breast cancer risk varied with age and dietary fat intake. Among women aged 50-59 years, with a fat intake in the lowest quartile, the risk of breast cancer increased with increasing consumption of alcohol. A consumption of 24 g or more per day was associated with an 18-fold increased risk compared with abstainers. For women in other age groups, alcohol consumption had no significant association with breast cancer risk. PMID- 1873456 TI - Epidemiologic leads to cancer control in India. PMID- 1873457 TI - Extremely low-frequency electric and magnetic fields and cancer. PMID- 1873458 TI - Nonmammalian vertebrate skeletal muscles express two triad junctional foot protein isoforms. AB - Mammalian skeletal muscles express a single triad junctional foot protein, whereas avian muscles have two isoforms of this protein. We investigated whether either case is representative of muscles from other vertebrate classes. We identified two foot proteins in bullfrog and toadfish muscles on the basis of (a) copurification with [3H]epiryanodine binding; (b) similarity to avian muscle foot proteins in native and subunit molecular weights; (c) recognition by anti-foot protein antibodies. The bullfrog and toadfish proteins exist as homooligomers. The subunits of the bullfrog muscle foot protein isoforms are shown to be unique by peptide mapping. In addition, immunocytochemical localization established that the bullfrog muscle isoforms coexist in the same muscle cells. The isoforms in either bullfrog and chicken muscles have comparable [3H]epiryanodine binding capacities, whereas in toadfish muscle the isoforms differ in their levels of ligand binding. Additionally, chicken thigh and breast muscles differ in the relative amounts of the two isoforms they contain, the amounts being similar in breast muscle and markedly different in thigh muscle. In conclusion, in contrast to mammalian skeletal muscle, two foot protein isoforms are present in amphibian, avian, and piscine skeletal muscles. This may represent a general difference in the architecture and/or a functional specialization of the triad junction in mammalian and nonmammalian vertebrate muscles. PMID- 1873459 TI - Differential polarization imaging. IV. Images in higher Born approximations. AB - The theory of differential polarization imaging developed previously within the framework of the first Born approximation is extended to higher Born approximations, taking into account interactions among the polarizable groups in the object. Several properties of differential polarization images, originally described using first Born approximation are modified when higher Born approximations are used. In particular, (a) when the polarizable groups are spherically symmetric, the off-diagonal Mueller elements Mij (i not equal to j) in bright field do not vanish in higher Born approximations, as they do in the first Born approximation case. (b) In higher Born approximations, the dark field Mi4 and M4i (i = 1, 2, 3) images do not vanish as in the first Born approximation, due to the anisotropy induced by the interactions among the groups. (c) When the polarizability tensor of each group is symmetric and real, the bright field M14 and M41 images always vanish in the first Born approximation. In higher Born approximations, these terms do not vanish if the groups bear a chiral relationship to each other. Quantitative criteria for the validity of the first Born approximation in differential polarization imaging are explicitly derived for three different types of media: (a) linearly anisotropic, (b) circularly anisotropic, and (c) linearly and circularly anisotropic (medium displaying linear birefringence and circular birefringence). These criteria define the limits of thickness and the degree of anisotropy of optically thin media. Finally, the possibility to perform optical sectioning in differential polarization imaging in the presence and absence of group interactions is discussed. PMID- 1873460 TI - Differential polarization imaging. V. Numerical aperture effects and the contribution of preferential scattering and absorption to the circular dichroism images. AB - Chiral objects which scatter and absorb preferentially left versus right circularly polarized light give rise to bright-field circular dichroism (CD) images containing contributions from both these two phenomena. These contributions are separated and characterized mathematically, and the effect of the dimensions of the chiral object on their relative magnitude is discussed. CD images of the long-range chiral organization of the thylakoid membranes in chloroplasts are obtained at two different wavelengths to illustrate the diverse wavelength dependence of the preferential absorption and scattering contributions to the images. The bright field CD images not only depend on the magnitude and sign of the preferential scattering and preferential absorption contributions, but also on the numerical aperture of the lens used. This dependence is obtained formally and a method to extract the angle dependent preferential scattering contributions to the images is presented. The validity of this method is confirmed experimentally. PMID- 1873461 TI - Model for the dynamic responses of taste receptor cells to salty stimuli. I. Function of lipid bilayer membranes. AB - The dynamic response of the lipid bilayer membrane is studied theoretically using a microscopic model of the membrane. The time courses of membrane potential variations due to monovalent salt stimulation are calculated explicitly under various conditions. A set of equations describing the time evolution of membrane surface potential and diffusion potential is derived and solved numerically. It is shown that a rather simple membrane such as lipid bilayer has functions capable of reproducing the following properties of dynamic response observed in gustatory receptor potential. Initial transient depolarization does not occur under Ringer adaptation but does under water. It appears only for comparatively rapid flows of stimuli, the peak height of transient response is expressed by a power function of the flow rate, and the membrane potential gradually decreases after reaching its peak under long and strong stimulation. The dynamic responses in the present model arise from the differences between the time dependences in the surface potential phi s and the diffusion potential phi d across a membrane. Under salt stimulation phi d cannot immediately follow the variation in phi s because of the delay due to the charging up of membrane capacitance. It is suggested that lipid bilayer in the apical membrane is the most probable agency producing the initial phasic response to the stimulation. PMID- 1873462 TI - On the relationship between distance information derived from cross-linking and from resonance energy transfer, with specific reference to sites located on myosin heads. AB - The techniques of fluorescence resonance energy transfer (FRET) and cross-linking can provide complementary information concerning the relative separation of a pair of sites. Cross-linking experiments provide an assessment of the distance of closest approach between a pair of sites. FRET measurements, by contrast, yield information about the average distance between the pair of sites. We have taken advantage of hybrid myosins to understand the relationship between distances obtained for a pair of equivalent sites, one on each myosin head, using both FRET (steady-state and time-decay) and cross-linking techniques. The rigid cross linker, 4-4'-dimaleimidyl-stilbene-2-2'-disulfonic acid (DMSDS), can efficiently cross-link the two myosin regulatory light-chains, each at residue Cys50 of the Mercenaria regulatory light chain (Chantler, P.D., and S. M. Bower. 1988. J. Biol. Chem. 263:938-944), indicating that these sites can come within 18 +/- 2 A of each other. In a complementary set of experiments, steady-state and time-decay measurements using fluorescence donor/acceptor pairs located at these same sites indicate transfer efficiencies of somewhat less than 20%, suggesting an average separation of greater than 50 A between sites (Chantler, P. D., and T. Tao. 1986. J. Mol. Biol. 192:87-99). Here, we present theoretical calculations which show that efficient cross-linking can be achieved readily in dynamic systems such as the heads of myosin, even though the necessary subpopulation of proximate molecules at any instant may be below the detection limits of time-decay-FRET. Therefore, cross-linking experiments can provide important ancillary information about the extent of motions within a marcomolecular system when used in conjunction with FRET.As a corollary, demonstration of extensive cross-linking does not necessarily indicate a static proximity; the mean separation distance should be ascertained by other methods such as FRET. PMID- 1873463 TI - Orientation of specifically 13C=O labeled phosphatidylcholine multilayers from polarized attenuated total reflection FT-IR spectroscopy. AB - Oriented multilayers of 1-myristoyl-2(1-13C)-myristoyl-sn-glycero-3 phosphatidylcholine (2[1-13C]DMPC) and 1-palmitoyl-2(1-13C)-palmitoyl-sn-glycero 3-phosphatidylcholine (2[1-13C]DPPC) were investigated by use of attenuated total reflection infrared spectroscopy with polarized light. Experiments were performed with the aim to determine the orientation of the two ester groups in these phospholipids in the solid state and in the hydrated state at temperatures below and above the respective gel to liquid-crystalline phase transitions. Substitution of the naturally occurring 12C carbonyl carbon atom by 13C in the ester group of the sn-2 chain of DMPC and DPPC shifts the infrared absorption of the carbonyl double bond stretching vibration to lower frequency. This results in two well-resolved ester C=O bands which can be assigned unequivocally to the sn-1 and sn-2 chains as they are separated by more than 40 cm-1. The two ester CO-O single bond stretching vibrations of the molecular fragments-CH2CO-OC-are also affected and the corresponding infrared absorption band shifts by 20 cm-1 on 13C labeling of the carbonyl carbon atom. From the dichroic ratios of the individual ester bands in 2(1-13C)DMPC and 2(1-13C)DPPC we were able to demonstrate that the sn-1 and sn-2 ester C=O groups are similarly oriented with respect to the bilayer plane, with an angle greater than or equal to 60 degrees relative to the bilayer normal. The two CO-O single bonds on the other hand have very different orientations. The CH2CO-OC fragment of the sn-1 chain is oriented along the direction of the all-trans methylene chain, whereas the same molecular segment of the sn-2 carbon chain is directed toward the bilayer plane. This orientation of the ester groups is retained in the liquid-crystalline phase. The tilt angle of the hydrocarbon all-trans chains, relative to the membrane normal, is 25 degrees in the solid state of DMPC and DPPC multibilayers. In the hydrated gel state this angle varies between 26 degrees and 30 degrees, depending on temperature. Neither the orientation of the phosphate group, nor that of the choline group varies significantly in the different physical states of these phospholipids. PMID- 1873464 TI - Time-resolved changes in equatorial x-ray diffraction and stiffness during rise of tetanic tension in intact length-clamped single muscle fibers. AB - We report the first time-resolved x-ray diffraction studies on tetanized intact single muscle fibers of the frog. The 10, 11, 20, 21, 30, and Z equatorial reflections were clearly resolved in the relaxed fiber. The preparation readily withstood 100 1-s duration (0.4-s beam exposure) tetani at 4 degrees C (less than 4% decline of force and no deterioration in the 10, 11 equatorial intensity ratio at rest or during activation). Equatorial intensity changes (10 and 11) and fiber stiffness led tension (t1/2 lead 20 ms at 4 degrees C) during the tetanus rise and lagged during the isometric phase of relaxation. These findings support the existence of a low force cross-bridge state during the rise of tetanic tension and isometric relaxation that is not evident at the tetanus plateau. In "fixed end" tetani lattice expansion occurred with a time course similar to stiffness during the tetanus rise. During relaxation, lattice spacing increased slightly, while the sarcomere length remained isometric, but underwent large changes after the "shoulder" of tension. Under length clamp control, lattice expansion during the tetanus rise was reduced or abolished, and compression (2%) of the lattice was observed. A lattice compression is predicted by certain cross-bridge models of force generation (Schoenberg, M. 1980. Biophys. J. 30:51-68; Schoenberg, M. 1980. Biophys. J. 30:69-78). PMID- 1873465 TI - Osmotically induced electrical signals from actin filaments. AB - Actin filaments, F-actin, a major component of the cortical cytoskeleton, play an important role in a variety of cell functions. In this report we have assessed the role of osmotic stress on the electrochemical properties of F-actin. The spontaneous Donnan potential of a polymerized actin solution (5 mg/ml) was -3.93 +/- 1.84 mV, which was linearly reduced by osmotic stress on the order of 1-20 mOsm (0.28 +/- 0.06 mV/mM). Calculated surface charge density was reduced and eventually reversed by increasing the osmotic stress as expected for a phase transition behavior. The electro-osmotic behavior of F-actin disappeared at pH 5.5 and was dependent on its filamentous nature. Furthermore, osmotically stressed F-actin displayed a nonlinear electric response upon application of electric fields on the order of 500-2,000 V/cm. These data indicate that F-actin in solution may display nonideal electro-osmotic properties consistent with ionic "cable" behavior which may be of biological significance in the processing and conduction of electrical signals within the cellular compartment. PMID- 1873466 TI - Monte Carlo simulation of miniature endplate current generation in the vertebrate neuromuscular junction. AB - A Monte Carlo method for modeling the neuromuscular junction is described in which the three-dimensional structure of the synapse can be specified. Complexities can be introduced into the acetylcholine kinetic model used with only a small increase in computing time. The Monte Carlo technique is shown to be superior to differential equation modeling methods (although less accurate) if a three-dimensional representation of synaptic geometry is desired. The conceptual development of the model is presented and the accuracy estimated. The consequences of manipulations such as varying the spacing of secondary synaptic folds or that between the release of multiple quantal packets of acetylcholine, are also presented. Increasing the spacing between folds increases peak current. Decreased spacing of adjacent quantal release sites increases the potentiation of peak current. PMID- 1873467 TI - Frequency and concentration windows for the electric activation of a membrane active transport system. AB - Previous work has shown that a simple four-state membrane transport system can interact with an oscillating electric field to become an active transport system if there is charge translocation associated with conformational changes of the transporter and if affinities of the transporter for the ligand on the two sides of membrane are different. The relationship between the transport flux and both the frequency of the applied field and the concentration of ligand have been examined based on the following assumptions: the rate of the electroconformational change of the transporter is much greater than that of the ligand association/dissociation reaction, and the oscillating electric field has a large amplitude. It was found that the transport flux depends strongly on the frequency of the field and on the concentration of the ligand and it displays a window of broad bandwidth both on the frequency and the concentration axes. The maximum concentration gradient, or the static head, which can be supported by this mechanism is shown to be constant for field frequencies smaller than the rate of the electroconformational change. The static head value diminishes completely when the field frequency exceeds the rate of the conformational change. The presence of an optimal field frequency has been shown experimentally in several membrane enzyme systems. The theory was applied to the description of Rb and Na pumping in human erythrocytes stimulated by an AC field. The prediction of a window for a ligand concentration and the static head value may be tested experimentally. In addition, the rate constants and the equilibrium constants of the four state model can be determined by measuring positions of windows, fluxes, and static head values under different experimental conditions. These results are equally applicable to the oscillation of pressure, membrane tension, substrate concentration, or temperature if these external parameters can induce functionally relevant conformational changes of the transporter. PMID- 1873468 TI - Reversible mechanosensitive ion pumping as a part of mechanoelectrical transduction. AB - To explain the ability of some mechanosensitive cells to reverse the process of mechanotransduction and to generate mechanical oscillations and emit sound, a piezo-conformational coupling model (PCC model) is proposed. The model includes a transport protein which changes either its volume (PV-coupling) or its area in the membrane (gamma A-coupling) when undergoing conformational transitions. Such a protein can interact with an oscillating pressure to pump ions and create a transmembrane gradient if the affinities of the protein for ions are different at the two sides of membrane. The frequency and concentration windows for mechanical energy transduction were determined. Under optimal conditions, the efficiency of energy transduction can approach the theoretical maximum of 100%. If the concentration gradient exceeds the static head value (quasi-equilibrium which can be built up and maintained by this transport system), the energy transduction reverses and the transporter becomes a generator of mechanical oscillations at the expense of a concentration gradient. Estimation of thermodynamic parameters of the pump shows that the PV-coupling model would require large pressure oscillations to work while the gamma A-coupling model could work in physiological conditions. The gamma A-coupling mechanism may be used by cells for two purposes. In the reverse mode, it can be a force generator for various applications. In the direct mode, it may serve bioenergetic purposes by harvesting the energy of mechanical oscillations and storing it in the form of a concentration gradient. This pump has an unusual thermodynamic feature: it can distinguish the two components of the electrochemical potential gradient,i.e., the concentration gradient and the electrical potential, the latter serving as a permissive switch to open, or close, the pump when the potential reaches the threshold value.Predictions of the PCC model and its probable involvement in biological mechanotransduction are dicussed. PMID- 1873469 TI - Conformational flexibility of the Cys 697-Cys 707 segment of myosin subfragment 1. Distance distributions by frequency-domain fluorometry. AB - The separation between Cys 697 (SH1) and Cys 707 (SH2) of the heavy chain of myosin subfragment-1 was previously measured by fluorescence resonance energy transfer with a donor linked to SH1 and an acceptor to SH2. In the present study the distribution of the distances between the two thiols was recovered from frequency-domain fluorometry. In the native state and in the presence of ligands such as MgADP, pyrophosphate, orthovanadate (Vi) and actin, we found wide distributions of the separations between SH1 and SH2 (11-16 A) comparable to that found in the random-coil state (20 A). These results suggest that the SH1-SH2 segment has a high degree of conformational flexibility even in native S1. The flexibility is not much affected by the physiological state of S1. However, the ligands MgADP, Vi and MgADP + Vi decrease significantly the mean SH1-SH2 distance from 27 to 17 A with the effect of MgADP+ Vi being the most pronounced. The anisotropy decay of donor-labeled S1 is biphasic with two rotational correlation times. The long component is decreased by these ligands from 289 to 93 ns, suggesting a more compact symmetric structure of S1 in the presence of the ligands. The complex S1(MgADP)Vi has been shown to be a stable analogue of S1(MgADP)Pi, an unstable intermediate that is generated in the actomyosin ATPase cycle during muscle contraction. Since the power stroke of muscle is accompanied by release of Pi from S1(MgADP)Pi, the present results are consistent with a model in which force generation can be accompanied by transition of S1 from a highly symmetric or compact structure to a more extended structure. PMID- 1873470 TI - Construction and evaluation of a frequency-domain epifluorescence microscope for lifetime and anisotropy decay measurements in subcellular domains. AB - The measurement of time-resolved fluorescence parameters in living cells provides a powerful approach to study cell structure and dynamics. An epifluorescence microscope was constructed to resolve multi-component fluorescence lifetimes and complex anisotropy decay rapidly in labile biological samples. The excitation source consisted of focused, polarized laser light modulated by an impulse-driven Pockels' cell; parallel acquisition of phase angles and modulation amplitudes at more than 40 frequencies (5-250 MHz) was obtained by multi-harmonic cross correlation detection. Lifetime decay was measured against standard solutions introduced into the light path proximal to the microscope objective. Anisotropy decay was measured by rotation of a Glan-Thompson polarizer in the emission path. Phase reference light was split from the beam proximal to the microscope. Optical components were selected to avoid depolarization and to optimize fluorescence detection efficiency. The dichoric was replaced by a 1 mm square mirror. Fitting routine statistics were optimized for model discrimination in realistic biological samples. Instrument performance was evaluated using fluorescein in H2O/glycerol and H2O/ethylene glycol mixtures and in Swiss 3T3 fibroblasts in monolayer culture. Objective depolarization effects were evaluated by measurement of anisotropy decay using objectives of different numerical aperture. Lifetime and anisotropy decay measured by microscopy (0.5 micron laser spot) agreed with data obtained by cuvette fluorimetry. New biological applications for time resolved fluorescence microscopy are discussed. PMID- 1873471 TI - Effect of supercoiling on the melting characteristics of heteropolynucleotides. AB - Considering a supercoiled DNA molecule, having equal numbers of two distinct types of base-pairs, it has been shown theoretically that even for the extreme cases of mixing of the two types of base-pairs in a supercoiled DNA, the melting temperatures as well as the melting curves do not differ significantly. This indicates that these properties are practically independent of the detailed base sequence when the molecule is a covalently closed one and may be replaced by an equivalent homopolynucleotide whose binding energy is equal to the average base pairing energy of the original DNA. This conclusion has been further supported by comparing the theoretical results with those obtained experimentally in the cases of polyoma DNA and phi X174 DNA. Finally, the effects of supercoiling on the cooperativity of melting and a few aspects of the differential melting characteristics of a supercoiled DNA have been discussed which provide a clear physical understanding of the process. PMID- 1873472 TI - Thermodynamics of hydrolysis of disaccharides. Lactulose, alpha-D-melibiose, palatinose, D-trehalose, D-turanose and 3-o-beta-D-galactopyranosyl-D-arabinose. AB - High-pressure liquid chromatography and microcalorimetry have been used to study the thermodynamics of the hydrolysis reactions of a series of disaccharides. The enzymes used to bring about the hydrolyses were: beta-galactosidase for lactulose and 3-o-beta-D-galactopyranosyl-D-arabinose; beta-glucosidase for alpha-D melibiose; beta-amylase for D-trehalose; isomaltase for palatinose; and alpha glucosidase for D-turanose. The buffer used was sodium acetate (0.02-0.10 M and pH 4.44-5.65). For the following processes at 298.15 K: lactulose(aq) + H2O(liq) = D-galactose(aq) + D-fructose(aq), K0 = 128 +/- 10 and delta H0 = 2.21 +/- 0.10 kJ mol-1; alpha-D-melibiose(aq) + H2O(liq) = D-galactose(aq) + D-glucose(aq), K0 = 123 +/- 42 and delta H0 = -0.88 +/- 0.50 kJ mol-1; palatinose(aq) + H2O(liq) = D-glucose(aq) + D-fructose(aq), delta H0 = -4.44 +/- 1.1 kJ mol-1; D trehalose(aq) + H2O(liq) = 2 D-glucose(aq), K0 = 119 +/- 10 and delta H0 = 4.73 +/- 0.41 kJ mol-1; D-turanose(aq) + H2O(liq) = D-glucose(aq) + D-fructose(aq), delta H0 = -2.68 +/- 0.75 kJ mol-1; and 3-o-beta-D-galactopyranosyl-D arabinose(aq) + H2O(liq) = D-galactose(aq) + D- arabinose(aq),0H0 = 107 +/- 10 and delta H0 = 2.97 +/- 0.10 kJ mol-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873473 TI - Thermodynamics of hydrolysis of oligosaccharides. AB - Microcalorimetry has been used to determine enthalpy changes for the hydrolysis of a series of oligosaccharides. High-pressure liquid chromatography was used to determine the extents of reaction and to check for any possible side reactions. The enzyme glucan 1,4-alpha-glucosidase was used to bring about the following hydrolysis reactions: (A) maltose(aq) + H2O(liq) = 2D-glucose(aq); (B) maltotriose(aq) + 2H2O(liq) = 3D-glucose(aq); (C) maltotetraose(aq) + 3H2O(liq) = 4D-glucose(aq); (D) maltopentaose(aq) + 4H2O(liq) = 5D-glucose(aq); (E) maltohexaose(aq) + 5H2O(liq) = 6D-glucose(aq); (F) maltoheptaose(aq) + 6H2O(liq) = 7D-glucose(aq); (G) amylose(aq) + nH2O(liq) = (n + 1) D-glucose(aq); and (H) panose(aq) + 2H2O(liq) = 3D-glucose(aq); (J) isomaltotriose(aq) + 2H2O(liq) = 3D glucose(aq). The enzyme beta-fructofuranosidase was used for the reactions: (K) raffinose(aq) + H2O(liq) = alpha-D-melibiose(aq) + D-fructose(aq); and (L) stachyose(aq) + H2O(liq) = o-alpha-D-galactopyranosyl-(1----6)- alpha-o-D galactopyranosyl-(1----6)-alpha-D-glucopyranose + D-fructose(aq). The results of the calorimetric measurements (298.15 K, 0.1 M sodium acetate buffer, pH 4.44 6.00) are: delta H0A = -4.55 +/- 0.10, delta H0B = -9.03 +/- 0.10, delta H0C = 13.79 +/- 0.15, delta H0D = -18.12 +/- 0.10, delta H0E = -22.40 +/- 0.15, delta H0F = -26.81 +/- 0.20, delta H0H = 1.46 +/- 0.40, delta H0J = 11.4 +/- 2.0, delta H0K = -15.25 +/- 0.20, and delta H0L = -14.93 +/- 0.20 kJ mol-1. The enthalpies of hydrolysis of two different samples of amylose were 1062 +/- 20 and 2719 +/- 100 kJ mol-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873474 TI - Electrostatic interaction between ion-penetrable multi-layered membranes. AB - A theory of the double layer interaction regulated by the Donnan potential between two ion-penetrable membranes in an electrolyte solution developed previously by Ohshima and Kondo is extended to the case in which the membranes consist of many layers having different thickness and densities of membrane-fixed charges. The interaction force is found to be determined mainly by the contributions from layers located within the depth of 1/kappa (kappa, Debye Huckel parameter) from the membrane surface. It is also predicted that the interaction force may alter its sign with changing electrolyte concentration. PMID- 1873475 TI - Thermodynamic parameters for the glutamate dehydrogenase catalyzed alpha-imino acid-alpha-amino acid interconversion. AB - Delta 1-Piperidine 2-carboxylic acid, an alpha-imino acid, is reduced by 1,4 dihydropyridines to pipecolic acid, an alpha-amino acid, and the corresponding pyridinium ions. This nonenzymatic reaction occurs only in the direction of pipecolic acid production. Glutamate dehydrogenase catalyzes this reaction when the reductant is NADPH and gives as products L-pipecolic acid and NADP+. The reaction velocity for the enzyme-catalyzed reaction is measurable in either direction. The pH-independent equilibrium constant, Keq, for the reduction of the imino acid by NADPH to give pipecolic acid anion and NADP+ was determined from the equilibrium conditions and the pKa values of pipecolic acid (10.72) and of the cyclic imino acid (8.10). The value of Keq was found to be 175 +/- 30; the values of delta G0, delta H0 and delta S0 are -3.1 +/- 0.1 kcal/mol, 5 +/- 1 kcal/mol and 27 +/- 4 e.u., respectively. The data indicate that the reactants are far more solvated than the products and that there must be a large degree of solvent reorganization during the course of the reaction. If these thermodynamic parameters apply to the redox step of the enzyme-catalyzed glutamate reaction, then the burst phase which results upon mixing the enzyme, L-glutamate and NADP+ in stoichiometric amounts must contain a hidden nonredox step of large delta H0 value to account for the curved Arrhenius plot observed for this phase (A.H. Colen, R.T. Medary and H.F. Fisher, Biopolymers 20 (1981) 879). PMID- 1873476 TI - Molecular cloning and sequence of porcine interleukin 6 cDNA and expression of mRNA in synovial fibroblasts in vitro. AB - Synovial fibroblasts, derived from enzyme digestion of porcine synovial tissue, released interleukin 6 (IL-6) bioactivity in culture and this release was enhanced by IL-1 alpha. The porcine IL-6 was cloned from a cDNA library made from these cells using human IL-6 cDNA as a probe. Clone PIL-6[13-8] was sequenced and coded for 212 amino acids with 62% homology and 42% homology to published sequences of human and mouse (or rat), respectively. The cDNA was used to probe the expression of pig IL-6 at the RNA level in pig synovial fibroblasts in vitro. IL-1 alpha and tumor necrosis factor markedly induced steady state levels of IL-6 at 20 h in serum-free conditions, whereas transforming growth factor-beta (TGF beta), epidermal growth factor, and 10% fetal calf serum did not. TGF-beta pretreatment dramatically inhibited TNF-induction of the IL-6 mRNA but did not markedly affect induction by IL-1 alpha. However, TGF-beta did reduce IL-6 activity detected in the supernatants of IL-1-induced cells. PMID- 1873477 TI - Inhibition of interleukin 1 synthesis by tenidap: a new drug for arthritis. AB - Tenidap is a new antiarthritic drug of novel chemical structure. This study shows the effects of tenidap on the in vitro synthesis of interleukin 1 (IL-1). IL-1 production by murine peritoneal macrophages was induced either by stimulation with lipopolysaccharide (LPS) or by phagocytosis of zymosan. With either stimulus, tenidap inhibited IL-1 production as measured by a quantitative competitive IL-1 receptor binding assay. Approximately 20 ng/mL of IL-1 was produced by 10(6) macrophages in response to LPS and about half that amount was produced in response to zymosan. Fifty percent inhibition of IL-1 production by tenidap was found at 3 microM for both stimuli. Using goat anti-IL-1 alpha and Western blot analysis, the appearance of intracellular 34 kDa pro-IL-1 alpha was inhibited by tenidap down to 3 microM. Tenidap decreased [35S]Met incorporation into cellular protein at 30 microM but not at 10 or 3 microM, indicating selectivity for IL-1 inhibition relative to total protein synthesis. Because tenidap inhibited IL-1 induction by both zymosan and LPS, it must act subsequently to receptor triggering. As the appearance of IL-1 was inhibited both intracellularly and extracellularly, the primary drug effect cannot be on secretion. PMID- 1873479 TI - Neutrophils can generate their activator neutrophil-activating peptide 2 by proteolytic cleavage of platelet-derived connective tissue-activating peptide III. AB - We have investigated the conditions that lead to the generation of the neutrophil activating peptide 2 (NAP-2) from its precursor, the platelet-derived connective tissue-activating peptide III (CTAP-III). Lysed platelets were found to contain predominantly CTAP-III in the cytosolic fraction, but further truncated derivatives, among these NAP-2, occurred tightly bound to the membrane fraction of fresh platelets. NAP-2 biological activity, as measured by the induction of enzyme release in human neutrophils [polymorphonuclear leukocytes (PMN)] was released by stimulated platelets to a low degree. Much higher activities were formed in the presence of peripheral blood leukocytes. Coincubation of CTAP-III with PMN resulted in the almost complete conversion of the precursor to NAP-2, as did incubation of CTAP-III with PMN-conditioned medium. In both situations, the generation of NAP-2 could be prevented by serine-protease inhibitor phenylmethylsulfonyl fluoride but not by inhibitors specific for Ca(2+)-dependent or thiol proteases. From several PMN-derived proteases tested, only cathepsin G had the capacity to cleave CTAP-III into NAP-2 with high specificity and in a relatively short period of time (30 min). Our data indicate that NAP-2, released by platelets in small quantities, could cause PMN to enter into a positive feedback cycle by initiating the secretion of serine proteases, which in turn could convert platelet-derived CTAP-III into biologically active NAP-2. PMID- 1873478 TI - Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome. AB - Chronic fatigue syndrome (CFS) is an idiopathic illness associated with a variety of immunologic abnormalities. To investigate potential pathogenetic mechanisms, we evaluated serum levels and peripheral blood mononuclear cell (PBMC) production of selected cytokines and immunoglobulins. Serum bioactive transforming growth factor beta (TGF-beta) levels were higher (P less than 0.01) in patients with CFS (290 +/- 46 pg/mL) than in control subjects (104 +/- 18 pg/mL), but levels of other cytokines tested were not different. Lipopolysaccharide-stimulated release of interleukin 1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha was increased (P less than 0.05) in PBMC cultures from patients with CFS versus control subjects; enhanced (P less than 0.01) IL-6 release to phytohemagglutinin was also observed. In contrast, TGF-beta release in response to lipopolysaccharide was depressed (P less than 0.01) in PBMC cultures derived from patients with CFS. No differences in IL-2 and IL-4 or immunoglobulin production were observed. The enhanced release of inflammatory cytokines by stimulated PBMC from patients with CFS suggests that these cells are primed for an increased response to immune stimuli. These data also suggest an association between abnormal regulation of TGF-beta production in vivo and in vitro with the immunologic consequence of CFS. PMID- 1873480 TI - Neutrophil-activating peptide 1/interleukin 8 mRNA expression and protein secretion by human monocytes: effect of cyclosporin A. AB - Neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8) is a recently described cytokine with potent chemotactic activity for human neutrophil granulocytes (PMN) and T cells. In psoriasis, a chronic hyperproliferative and inflammatory skin disorder, PMN and T cells are found as prominent cells in the inflammatory infiltrate of the lesions; however, monocytes were shown to be the first cells invading a newly formed plaque. NAP-1/IL-8 was found to be present in high amounts in the skin and in scale material of psoriatic patients. Psoriasis responds well to systemic treatment with cyclosporin A (CsA), an immunosuppressive peptide. Therefore, we addressed the question of whether the clinical improvement of psoriatic patients during CsA therapy may be due to an inhibition of NAP-1/IL-8 production and secretion from monocytes. Purified human monocytes were stimulated by lipopolysaccharide in the presence or absence of various concentrations of CsA. Production of NAP-1/IL-8 was determined as expression of specific mRNA by fluorescent in situ hybridization. Secreted peptide was measured by bioassay (PMN chemotaxis) and enzyme-linked immunosorbent assay (ELISA) using specific monoclonal antibodies. The results show that CsA neither inhibited mRNA expression for NAP-1/IL-8 nor secretion of the peptide. These findings support the hypothesis that the pharmacological effect of CsA may be restricted to the inhibition of T-cell activation and proliferation. PMID- 1873481 TI - Role of prostaglandins in the behavioral changes induced by murine interleukin 1 alpha in the rat. AB - Continuous infusion of murine recombinant interleukin 1 alpha (rIL-1 alpha) produces weight loss, appetite suppression, reduction in horizontal locomotor activity (crossovers) and vertical locomotor activity (rears), and an increase in drinking behavior in the rat. The role of prostaglandins (PG) in the elicitation of these effects was studied. Infusion of rIL-1 alpha produced a transient increase in serum (PGs) which peaked at 24 to 48 h. This increase was completely inhibited by piroxicam. However, inhibition of circulating PG by piroxicam did not block the reductions in appetite, crossover, and rears induced by rIL-1 alpha; it restored normal drinking behavior and only partially restored body weight. Continuous intraperitoneal infusion of PGE2 at 24 micrograms/day exposed the animals to serum levels of PGE2 comparable to those produced by infusion with rIL-1 alpha. Yet, at the point of maximum weight loss induced by rIL-1 alpha (72 h), PGE2 infusion resulted in only a quarter of the weight loss. Compared with rIL-1 alpha, continuously infused PGE2 produced significantly smaller reductions in appetite, crossovers, and rears, and had no effect on drinking behavior. From these observations, we conclude that the rIL-1 alpha-induced increase in drinking behavior was fully dependent on products of the cyclooxygenase pathway, but not necessarily PGE2. However, because of the failure of piroxicam to fully reverse rIL-1 alpha effects on eating, mobility, and weight loss, there must also be a significant PG-independent component to account for the full range of rIL-1 alpha effects. PMID- 1873482 TI - Analysis of interleukin 5 receptors on murine eosinophils: a comparison with receptors on B13 cells. AB - The interleukin 5 receptor (IL-5R) on murine eosinophils and a mouse B cell line (B13) was investigated using iodinated murine IL-5 produced in the baculovirus system. Electrophoretic analysis of this recombinant protein identified a range of bands Mr 26,000 to 32,000 resulting from differential glycosylation. The specific activity and binding kinetics of the iodinated IL-5 (125I-IL-5) were essentially identical to unlabeled material. Both high-affinity (Kd approximately 50 pM) and low-affinity (Kd approximately 1 nM) receptor populations were identified on murine eosinophils. Approximately 50 high-affinity receptors and 10,000 low-affinity receptors were present. This was compared with approximately 2,000 high-affinity (Kd approximately 80 pM) and about 8,000 low-affinity (Kd approximately 3 nM) sites on B13 cells. An antibody that inhibits IL-5 binding to, and proliferation of, B13 cells (R52.120) was also shown to inhibit eosinophil proliferation, suggesting that eosinophils and B cells bear the equivalent IL-5 binding proteins. PMID- 1873483 TI - Augmented interleukin 6 production by rat thyrocytes (FRTL5): effect of interleukin 1 beta and thyroid-stimulating hormone. AB - This study shows that rat thyroid follicular (FRTL5) cells can produce interleukin 6 (IL-6) spontaneously and that IL-1 beta enhanced the production of IL-6 dose-dependently. In addition, 10 ng/mL of IL-1 beta in combination with 10 to 1,000 microU/mL of thyroid-stimulating hormone (TSH) synergistically enhanced IL-6 production. It is suggested that IL-6 released from thyroid follicular cells may be a costimulator of autoreactive B and T cells in autoimmune thyroid disease and may constitute another link between the immune and endocrine systems. PMID- 1873485 TI - Osteoclasts: structure and function. AB - Osteoclasts are multinucleated giant cells showing specialized membrane structures, clear zones and ruffled borders, which are responsible for the process of bone resorption. These cells arrive at the resorption site via the bloodstream as mononuclear cells, derived from haemopoietic precursors in the spleen or bone marrow, which fuse prior to resorption. The osteoclast may share an early progenitor cell, the granulocyte macrophage colony-forming unit (GM-CFU) with monocytes, macrophages and granulocytes, implying that osteoclasts share the pluripotent haemopoietic stem cell with all other haemopoietic cells. In the past, elucidation of the structure of these cells relied upon traditional ultrastructural techniques. Transmission electron microscopic studies revealed details of the unique ultrastructure of these cells and, in combination with stereological techniques, showed the response of cells to various hormonal stimuli. Scanning electron microscopy not only demonstrated the surface appearance of osteoclasts, and their predilection for spreading on various substratum components, but has also been used as an adjunct in resorption assays in which areas of resorption lacunae are measured as indicators of cell activity. Recent advances in fields such as immunocytochemistry and freeze fracture techniques have contributed towards a more detailed delineation of antigenic profile, cytoskeletal structure and localization of enzymatic pathways. The osteoclast is subject to extensive regulatory mechanisms and it has been established that the osteoblast plays a major role in mediating the effects of osteotropic hormones and local mediators on these cells. Hence, research aimed at elucidating the coupling mechanisms between these two cells may result in new therapies for bone disease. PMID- 1873484 TI - Eosinophil differentiation of human umbilical cord mononuclear cells and prolonged survival of mature eosinophils by murine EL-4 thymoma cell conditioned medium. AB - Umbilical cord mononuclear cells, HL-60 cells, HL-60 clones selected for eosinophil differentiation, and the eosinophil leukemia cell line EoL were tested for their ability to produce eosinophil peroxidase. HL-60 clones selected for eosinophil differentiation produced eosinophil peroxidase, as judged by staining of cells for cyanide-resistant peroxidase activity; however, these cells lost their ability to produce eosinophil peroxidase in long-term culture. In contrast, eosinophil precursors from human umbilical cord blood mononuclear cells stimulated with murine EL-4 conditioned medium (EL-4 CM) were regularly induced to eosinophil protein synthesis, including eosinophil peroxidase, major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin, as assessed by cyanide-resistant peroxidase and immunofluorescence staining. This induction by EL-4 CM is either at the level of gene transcription or mRNA stabilization, as shown by the increase of total mRNA for eosinophil peroxidase, major basic protein, and eosinophil-derived neurotoxin by Northern blot analyses. Purified peripheral blood eosinophils incubated for 4 days with EL-4 CM had increased survival over control eosinophils. Moreover, this enhanced survival was specifically blocked by antiserum to interleukin 5. Our results suggest that the effects of EL-4 CM on human umbilical cord mononuclear cells and mature eosinophils are due to the presence of interleukin 5. PMID- 1873486 TI - Ultrastructure of the normal human placenta. AB - In this review, the ultrastructure of the normal human chorionic villus is examined and illustrated. The outer covering of trophoblast, comprising the generative cytotrophoblast and the multinucleated syncytiotrophoblast which is derived from it, is described, including such features as the microvillous surface, vesicles and vacuoles, endoplasmic reticulum and secretory droplets. The structure, composition, development and inclusions of the trophoblastic basement membrane are discussed, and the ultrastructure of the various components of the stroma, including reticulum cells, fibroblasts, Hofbauer cells, capillaries and the non-cellular matrix are illustrated and described, with special reference to their inter-relationships and function. PMID- 1873487 TI - Ultrastructural morphometry of human leucocytes in health and disease. AB - In this review, the literature on ultrastructural morphometry of each of the main types of human blood leucocytes has been considered, together with the technical and numerical procedures essential for valid analysis. Quantitative data have been reported for these cell types in health and comparisons have been made with those in disease states. In monocytes, and in macrophages developing from them, subtle ultrastructural differences have been detected and quantitated in malignant lymphoma; as the mononuclear phagocytes were not themselves neoplastic, the changes may have related to defects in host defence. Change in the ultrastructural characteristics of leukaemic monoblasts have also been reported. Lymphocytes and malignant lymphoid cells have been extensively investigated: differences between different types and subsets have been shown to be present in both normal lymphocytes and their malignant counterparts in leukemias and lymphomas. Particular attention has been paid to morphometric assessment of nuclear shape and size in these disorders and to its possible value as a diagnostic tool. Granulocytes have so far been the subject of few morphometric studies, although in hypereosinophilic syndrome, cellular changes have been defined and have thrown light on the abnormal pattern of degranulation. There have also been scattered reports on the cells of acute myelogenous leukaemia. The use of computers and sophisticated statistical packages has greatly facilitated the application of multiple comparison procedures and has permitted discriminant analysis to be carried out where appropriate. This review shows that ultrastructural morphometry of leucocytes will have an increasing application in clinical pathology. PMID- 1873488 TI - Localization of nucleolar chromatin by immunocytochemistry and in situ hybridization at the electron microscopic level. AB - Nucleoli are the morphological expression of the activity of a defined set of chromosomal segments bearing rRNA genes. The topological distribution and composition of the intranucleolar chromatin as well as the definition of nucleolar structures in which enzymes of the rDNA transcription machinery reside have been investigated in mammalian cells by various immunogold labelling approaches at the ultrastructural level. The precise intranucleolar location of rRNA genes has been further specified by electron microscopic in situ hybridization with a non-autoradiographic procedure. Our results indicate that the fibrillar centers are the sole nucleolar structures where rDNA, core histones, RNA polymerase I and DNA topoisomerase I are located together. Taking into account the potential value and limitations of immunoelectron microscopic techniques, we propose that transcription of the rRNA genes takes place within the confines of the fibrillar centers, probably close to the boundary regions to the surrounding dense fibrillar component. PMID- 1873489 TI - In vivo delivery of interleukin-6 using vaccinia virus: effects on T lymphocytes in nude mice. AB - We have constructed a recombinant vaccinia virus (VV) expressing the human interleukin-6 (IL-6) gene, VV(IL-6). After injection of VV(IL-6) i.v. into Balb/c mice, circulating IL-6 was detected during 3 days with the peak activity on day 4, indicating that VV injection is an effective method to deliver lymphokines in vivo. We have further examined the effects of IL-6 in vivo in immunodeficient mice. Nude mice were injected i.v. with VV(IL-6). Ten days after the injection, mice were sacrificed and spleen cells were obtained. Spleen cells from VV(IL-6) injected mice proliferated remarkably in response to IL-2, while spleen cells from mice injected with unrelated VV manifested no particular proliferation in response to lymphokines. When spleen cells were further cultured in vitro for 5 days in the presence of Concanavalin-A stimulated rat spleen cell supernatant (Con-A factor), CD4 or CD8 positive cells were detected in the VV (IL-6) injected group, while few positive cells were detected in the control groups. These results suggest that IL-6 stimulates nude mice spleen cells in vivo, to a stage where they are able to proliferate in response to IL-2, or to differentiate into CD4 or CD8 positive cells in presence of rat Con-A factor. PMID- 1873490 TI - Purification and characterization of the immunostimulatory properties of recombinant human interleukin-1 beta. AB - In this study we have used a new method for human recombinant IL-1 beta (rIL-1 beta) purification and investigated its immunostimulatory biological activity. The IL-1 beta gene was cloned using a novel mRNA preparation from activated human blood monocytes. The purification protocol consists of extraction and two chromatographic steps using the new Soloza cation exchange resin. The purified protein was characterized electrophoretically, by amino acid analysis and reverse phase chromatography. The protein migrated on SDS-PAGE with a molecular weight of 18.200 but demonstrated the minor presence of aggregates (dimers and trimers). Specific activity of purified rIL-1 beta in comitogenic assay on mouse thymocytes was 10(8) U/mg protein. rIL-1 beta increased in a dose dependent manner proliferation of Con A-stimulated murine thymocytes, splenocytes, PHA-stimulated human peripheral blood lymphocytes and transformed B-cell lines. Comitogenic activity depended on the degree of lymphocyte preactivation and was similar to that of natural human IL-1 beta. rIL-1 beta enhanced IL-2 production by murine spleen cells and EL-4 cell line and IL-2 receptor expression by human peripheral blood mononuclear cells. It induced PGE2 release from human blood monocytes but had no effect on human neutrophil chemotaxis, phagocytosis and respiratory burst. PMID- 1873491 TI - Picogram concentrations of endotoxin stimulate synthesis of IL-1 beta and TNF alpha by human peripheral blood mononuclear cells exposed to recombinant human C5a. AB - Endotoxemia, complement activation, and the generation of C5a occur in the course of sepsis, trauma, and the adult respiratory distress syndrome, clinical situations in which TNF and IL-1 are thought to play an important role. In the present studies, we examined the effect of picogram concentrations of endotoxin (LPS) on the synthesis of IL-1 beta and TNF alpha by human PBMC exposed to recombinant human C5a (rhuC5a). rhuC5a induced the synthesis of IL-1 beta by PBMC made in response to otherwise substimulatory levels of LPS. In the presence of rhuC5a, LPS concentrations from 10 pg to 1000 pg/ml substantially amplified IL-1 beta synthesis by PBMC compared to LPS alone. Since rhuC5a can induce transcription of IL-1 beta with minimal translation to cytokine protein, these studies support the concept that fM concentrations of LPS can combine with rhuC5a to provide the "second signal" for optimal translation of IL-1 beta mRNA. PMID- 1873492 TI - Differential biological activities of human interleukin-1 alpha and interleukin-1 beta. AB - We examined the biological effects induced by both human recombinant interleukin 1 alpha (IL-1 alpha) and beta (IL-1 beta) in five different cell types of human, rat and mouse origin. IL-1 alpha and beta preparations were standardized in terms of biological activity in the EL-4/CTLL bioassay and, in parallel, employed to stimulate PGE2 secretion in human fibroblasts, mesangial cells (MC), C57B1/6 mouse MC, DBA/2 mouse macrophages and Sprague Dawley rat MC. In addition, the co mitogenic effects of IL-1 alpha and beta were determined in freshly prepared Sprague Dawley rat thymocytes. No significant differences in IL-1 alpha and beta concentration dependent PGE2 production were detectable in the different cell types (MC, fibroblasts and macrophages) of human or mouse origin. Incubation of Sprague Dawley rat MC with both IL-1 alpha and beta resulted in a concentration dependent production of PGE2. However, in contrast to mouse or human MC the potency of IL-1 beta to induce PGE2 in Sprague Dawley rat MC was 26-fold higher compared to IL-1 alpha. In addition, the potency of IL-1 beta to enhance co stimulated proliferation of Sprague Dawley thymocytes was 200-fold higher than that of equal biological activities of IL-1 alpha. When we tested the additive effects on Sprague Dawley cells, increasing IL-1 beta concentrations added to a fixed IL-1 alpha concentration resulted in a cumulative rise in both, PGE2 secretion by MC and thymocyte proliferation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873493 TI - Mechanism of acute toxicity of IL-1 beta in mice. AB - Human recombinant IL-1 beta was able to kill C3H/HeJ mice only when inoculated intravenously at very high doses. IL-1 beta, inoculated at 100 mg/kg i.v. as a bolus, induced a shock-like state characterized by anorexia, severe hypothermia and hypoglycemia and persistent neutrophilia, leading to death in 55% of animals generally between 24 and 48 h. In contrast, the noninflammatory adjuvant IL-1 beta peptide VQGEESNDK (position 163-171) did not induce any toxic effect in vivo, when administered following the same schedule. At variance with what was previously observed in endotoxin induced shock, IL-1 beta induced death was not preceded by appearance of circulating TNF. On the other hand, very high and persistent levels of circulating IL-6 could be detected after lethal IL-1 beta administration. Treatment of mice with ibuprofen or with chlorpromazine, both known to counteract some of the toxic effects of IL-1 in vivo, could protect from IL-1 beta induced mortality. Both drugs, at doses protecting from IL-1 beta induced death, were able to abolish IL-1 beta-induced rise of circulating phospholipase A2 (PLA2) activity, and the subsequent generation of toxic PLA2 derived metabolites. PMID- 1873494 TI - Cell lines of novel type derived from a diabetic secrete tissue-reactive human monoclonal antibodies. AB - Human monoclonal antibodies have been produced from lymphocytes of an acute-onset insulin-dependent diabetic patient. Peripheral blood lymphocytes were hybridized with a fusion partner HMY-1320. Initial screening of human immunoglobulin secretion was made by a nitrocellulose dot blot assay. Ten stable cell lines of novel type, secreting human immunoglobulin, were obtained. These cell lines have been maintained in continuous culture over 6 months and cryopreserved in liquid nitrogen for 14 months. Human monoclonal antibodies of IgG and IgM class have been produced and are secreted at a rate of 150-650 ng/ml/10(6) cells/day. Monoclonal antibodies were tested for histological staining against a variety of endocrine and non-endocrine tissues. One monoclonal antibody, LT1E12, demonstrates a staining pattern in human, rat, and mouse tissues, similar to that of mitochondrial antibodies. Another antibody, LT3C4, demonstrates weak staining of smooth muscle in rat and mouse kidney sections. Neither specificities were detected in the diabetic patient's serum. The variety of immune tissue specificities obtained in this study demonstrates the potential value of human monoclonal antibodies as probes to analyze the complexity of autoimmunity in diabetes mellitus. PMID- 1873495 TI - Effect of production method on the systemic clearance rate of a human monoclonal antibody in the rat. AB - Pharmacologic studies of human immunoglobulins (IgM) in non-primate animal models, whether directed toward efficacy or toxicity, rely on pharmacokinetic parameters to achieve optimal doses and schedules. In rodents, human IgMs have an effective circulatory half-life of 11 h and a plasma clearance rate of 0.044 ml/min/kg. Studies of a new group of human monoclonal antibodies (hMAb) specific for Gram-negative bacteria and endotoxin revealed an IgM molecule, hMAb-10058, which, when purified from tissue culture medium, exhibited a suprisingly short circulatory lifetime in rodents. Investigations into possible explanations for this short circulatory half-life resulted in the development of a simple and efficient method for producing hMAbs in the immunodeficient NIH-3 mouse (bg x nu x XID). This method of production of hMAb-10058 had dramatic effects on its half life. Whereas hMAb-10058 produced in serum-free, defined medium had a clearance rate of 14.4 ml/min/kg and an effective half-life of 0.12 h, the same hMAb-10058 raised in mouse ascites had a decreased clearance rate of 0.092 ml/min/kg and an increased effective half-life of 12 h. This 100-fold enhancement of the hMAb's half-life was not affected by the purification process. Some potential molecular structures involved in the circulatory half-life of this hMAb are discussed. PMID- 1873496 TI - Generation of hybrid hybridomas secreting human IgM class hybrid antiricin and antidiphtheria toxin antibodies. AB - Two lines of mouse-human hybridomas were fused to produce human bifunctional antibodies. A hybridoma that secretes human IgM (kappa) class antiricin monoclonal antibody was treated with actinomycin D to inhibit cell growth. Another cell line, secreting human IgM (lambda) class antidiphtheria toxin monoclonal antibody, was 6-thioguanine resistant (HAT sensitive). Six hybridomas secreting IgM with both kappa and lambda light chains were obtained. Two of them secreted antibodies with antiricin specificity (kappa and lambda light chains) and antidiphtheria toxin specificity (kappa and lambda light chains). Antidiphtheria toxin antibodies secreted from other hybrid hybridomas did not contain kappa light chain, but lambda chain. A hybrid hybridoma clone 5-29 secreted complete hybrid IgM with lowered affinity to diphtheria toxin. These results suggested unbalanced recombination of immunoglobulin polypeptide chains in hybrid hybridomas. PMID- 1873497 TI - Monoclonal antibodies to human tumor nucleolar antigens: probes for studying biological function and determining clinical significance. AB - Using novel strategies, monoclonal antibodies (MAbs) were developed to two proliferation-associated nucleolar antigens. These two new antigens, termed P145 and P120, according to their molecular weights, were found in a broad range of tumor tissues. Overall, P120 was more restricted in its distribution than P145 because it was absent from many benign tumors and some malignant tumors. Using the MAbs as probes, antigens P145 and P120 were localized to separate nucleolar components. P145 was mainly associated with high molecular weight nucleolar RNPs. Antigen P120 was localized to a novel beaded microfibril found in a nucleolar residue fraction. DNAse and high salt treatment of this fraction provided optimal extraction of the P120 antigen. P145 and P120 differed from other proliferation associated nuclear/nucleolar antigens identified by autoimmune sera and by other MAbs. In PHA stimulated lymphocytes, both antigens were expressed in early G1 prior to or concurrent with increased RNA Pol I transcription. Microinjection of tumor cells with the P120 MAb inhibited cell proliferation and blocked the appearance of nucleolar pleomorphism that is characteristic of tumor cells. Clinical studies showed that P145 was not detected in normal bone marrow but was expressed in leukemic marrows (AML); the percentage of P145 positive cells correlated with percentage of malignant blasts (Raza et al., Am. Soc. Hematology, 1990). Antigen P145 was detected in 10 of 39 marrows from patients in complete remission. This result suggested that these cells have a higher proliferative potential than normal stem cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873498 TI - Generation and characterization of secreting and nonsecreting human x mouse heterohybridomas obtained by in vitro immunization of human peripheral blood lymphocytes. AB - Among the immortalizing fusion partners usable in the development of human monoclonal antibodies, nonsecreting human-mouse heteromyelomas are the most interesting. In vitro immunization of human peripheral blood lymphocytes (pretreated with leucine-O-methyl ester) with an immunogen, hemocyanin, before fusion, is a good methodology for generating nonsecreting heterohybrids. Their biological features have been extensively studied with particular attention to the level of human DNA. These heterohybrids retained more than 10% human DNA in the whole genome. However, nonsecreting heteromyeloma SHMD33 used as reference has 1% human DNA. There is no significant difference between the level of human DNA in the nonsecreting heteromyelomas and that of the secreting parent heterohybrid. The loss of human immunoglobulin production by the nonsecreting clones is not necessarily related to the diminution of human DNA. The presence of plasma cells containing human intracytoplasmic immunoglobulins and the lack of any antibody in the supernatant culture of nonsecreting clones show that the blockage of human antibody production could occur at the secretory stage. PMID- 1873499 TI - Serodiagnosis of cancer using porcine carboxypeptidase A as an animal antigen recognized by human monoclonal antibody HB4C5. AB - Protein from hog which is recognized by human monoclonal antibody (HB4C5), generated from a patient with large cell lung carcinoma, was identified as carboxypeptidase A by comparison of the protein with carboxypeptidase A in enzymatic activity, immunologic reactivity, and amino acid sequence. Carboxypeptidase A activity was also found in human cancer tissue, and purified antigen from cancer tissue recognized by the antibody HB4C5 was reacted with rabbit anti-carboxypeptidase A serum, indicating that carboxypeptidase A is an antigen of HB4C5. Since large amounts of carboxypeptidase A can be obtained from porcine sources, a simple method for its purification was established. The fraction which was most reactive with HB4C5 was obtained from acetone powder of porcine pancreas by successive applications of water extraction, ammonium sulfate precipitation, trypsin treatment, and Mono Q column chromatography. Its apparent molecular weight was 40,000, according to SDS polyacrylamide gel electrophoresis. When the reactivity of IgG in sera with the purified carboxypeptidase A was measured, the detection rates for lung, ovary, larynx, uterus, and liver cancer were more than 50%, while the rates for stomach and breast cancer were around 30%, and pancreatic cancer, benign diseases, and normal controls were minimally detected. PMID- 1873500 TI - Chimeric mouse-human anti-carcinoma antibodies that mediate different anti-tumor cell biological activities. AB - Two chimeric mouse-human antibodies, ING-1 (IgG1, kappa) and ING-2 (IgG1, lambda), have been constructed starting from anticarcinoma mouse hybridomas. These antibodies bind to different tumor-associated antigens which are present on human breast carcinoma cell lines at 10(5)-10(6) antigens/cell; ING-1 binds to a 40-kD membrane glycoprotein, while ING-2 binds to a glycoprotein of greater than 300 kD. In competitive binding experiments, both chimeric antibodies have identical binding activity to the parental mouse antibodies. The antibody dependent cellular cytotoxicity (ADCC) and complement-dependent cytolysis (CDC) activities of these antibodies were studied on carcinoma target cell lines. ING-1 mediates potent ADCC, but ING-2 had undetectable or very weak ADCC activity. ING 2 ADCC activity was significantly reduced by the addition of human serum, but ING 1 ADCC was unaffected. Neither ING-1 nor ING-2 mediated CDC of breast carcinoma cell lines, but ING-1 mediated CDC of a colon carcinoma cell line. ING-1 antibody antigen complexes are stable on the target cell surface for at least 2 hours, while much of bound ING-2 is lost from the surface of cells due to internalization or shedding. The activities of these antibodies confirm that the target antigen plays an important role in the biological effector functions triggered by cell-surface-bound antibodies. Both of these chimeric antibodies are candidates for further study as immunoconjugates for cancer diagnosis or therapy, and the unconjugated ING-1 antibody has promise for cancer therapy due to its potent activation of ADCC. PMID- 1873501 TI - Histone H2B as an antigen recognized by lung cancer-specific human monoclonal antibody HB4C5. AB - Histone H2B was demonstrated to be an immunoreactive material recognized by the human monoclonal antibody HB4C5, which had been already established to be specific for lung cancers. The inhibitory effect of histone H2B on the activity of HB4C5 antibody to immunostain the cytoplasmic antigen in lung adenocarcinoma tissue indicated that histone H2B at least had antigenic determinant comparable to the cytoplasmic antigen. A mouse anti-histone H2B monoclonal antibody could immunostain the cytoplasm of lung adenocarcinoma cells in sliced tissue sections in the same manner as the human monoclonal antibody HB4C5. Enzyme-linked immunosorbent assay of HB4C5 antibody on plastic immunoplates coated with histone H2B also showed specific reactivity of this antibody with histone H2B, and the reaction was effectively inhibited when extra histone H2B or mouse anti-histone H2B monoclonal antibody was added to the reaction mixture. These results consistently lead us to a conclusion that histone H2B possesses antigenicity to the human monoclonal antibody HB4C5. PMID- 1873502 TI - Characterization of a lung cancer-associated human monoclonal antibody HB4C5. AB - A human monoclonal antibody HB4C5, which is known to be associated with lung cancers, was characterized. Two kinds of light chains with 30-kD and 32-kD molecular mass were found to comprise the molecule of this IgM antibody. Various combinations of the two light chains could be contained in this IgM antibody molecule, which might have resulted in the heterogeneity of this antibody with different reactivities. The presence of the 30-kD light chain was indispensable for the antibody activity of cancer recognition. Monomeric 180-kD units of the antibody, having 32-kD light chains exclusively, which showed marginal activity of cancer recognition, could be removed by immunosorbent column chromatography with histone H2B-Sepharose 4B. F(ab')2 of the HB4C5 antibody containing the active 30-kD component as the dominant light-chain constituent could be purified by hydroxyapatite chromatography by HPLC, facilitating clinical applications of this lung cancer-associated monoclonal antibody of human origin. PMID- 1873503 TI - Construction of reshaped human antibodies with HIV-neutralizing activity. AB - Mouse monoclonal antibody (mAb) 0.5 beta binds to the envelope protein gp120 of human immunodeficiency virus (HIV) and neutralizes infection by HIV in vitro. Mouse mAb 0.5 beta, therefore, has potential as a therapeutic agent for the prevention and treatment of acquired immunodeficiency syndrome (AIDS). Since mouse mAbs are highly immunogenic in humans, efforts are being made to humanize mouse mAbs that are being considered for use in humans. This report describes the design, construction, and expression of reshaped human 0.5 beta antibodies. In these antibodies, the entire constant (C) regions were derived from human sequences. The variable (V) regions were derived from human framework regions (FRs) and mouse 0.5 beta complementarity determining regions (CDRs). One version of reshaped human 0.5 beta light (L) chain and six versions of reshaped human 0.5 beta heavy (H) chain were made and tested. Following transient expression in cos cells, all of the constructions were capable of producing humanlike antibody. Three of the H chain constructions (RHc, RHe, and RHf), when co-expressed with the L chain construction (RL), produced reshaped human antibody capable of binding to the epitope on gp120 recognized by mouse 0.5 beta mAb. The best version (RL + RHe) of reshaped human 0.5 beta antibody had both binding affinity and neutralizing activity that were within twofold that of the mouse or chimeric 0.5 beta antibody. PMID- 1873504 TI - In vitro immunization of human B lymphocytes. MAPPing of lymphokine specific mRNA and the effect of recombinant factors. AB - The kinetics of lymphokine-specific DNA transcription during in vitro immunization of human peripheral blood lymphocytes and splenocytes were studied using the polymerase chain reaction. The levels of specific mRNA were shown to be down regulated by cytolytic L-leucyl-leucine methyl ester-sensitive lymphocytes. In in vitro immunizations using L-leucyl-leucine methyl ester-treated human PBL or splenocytes, the lymphokine mRNA expression pattern indicated an active gene transcription during the entire stimulation period, especially for the IL-2 and IL-5 genes. Transcription of IL-6 and TNF beta started on day 4, whereas IFN gamma mRNA reached its maximum level on day 4. In vitro immunizations of cells not treated with L-leucyl-leucine methyl ester revealed a transient transcription of lymphokine DNA that was declining already after day 2. Exogenously added recombinant IL-2, IL-4, and IL-6 all exhibited a positive immunoregulatory effect on Ig secretion, whereas IL-5 was not found to have any effect on immunoglobulin secretion during the in vitro culture. These results present the first information useful for designing in vitro immunization systems based on recombinant lymphokines and antisense DNA for gene regulation. PMID- 1873506 TI - Drugs and the liver. Part 1: Testing liver function. PMID- 1873505 TI - Hybridoma-derived human suppressor factors: inhibition of growth of tumor cell lines and effect on cytotoxic cells. AB - With the objective of developing human T-T cell hybrids producing B-cell growth factor, we fused concanavalin A-activated T lymphocytes with cells of the Jurkat T cell line. The hybrids were selected on the basis of their ability to form colonies in soft agar, whereas the parent Jurkat T cell line did not. T-T cell hybrids were HLA-typed, screened by functional tests, and recloned by limiting dilution. In addition to obtaining B-cell growth factor-producing hybrids, we also obtained certain other T-T cell hybrids (as determined by HLA-typing) producing suppressor factors inhibiting proliferative responses and antibody production by human lymphocytes. Subsequently, a suppressor factor with similar inhibitory properties was identified in supernatants of the Jurkat T cell line. However, the Jurkat factor exhibited different biochemical and functional properties than the hybridoma-derived suppressor factors. Using two-parameter cell cycle analysis and the metachromatic fluorochrome acridine orange, we found that the hybridoma-derived 160 and 169 suppressor factors arrested phytohemagglutinin-induced proliferative of peripheral blood mononuclear cells in the G0/G1 phase of the cell cycle, whereas the Jurkat suppressor factor arrested proliferation in the S phase. Incubation of peripheral blood mononuclear cells with the 160, 169, or Jurkat suppressor factors for 24 hr at 37 degrees C, followed by washing, did not alter their cell cycle progression (or RNA content) in response to stimulation with phytohemagglutinin. The hybridoma-derived 160 and 169 suppressor factors and the Jurkat factor inhibited the growth but not the viability of cells from the following human tumor cell lines: A673 sarcoma cell line, SK-LC-6 and SK-LC-14 lung cell lines, SB, Raji, and Daudi lymphoblastoid cell lines, and FARR malignant melanoma cell line. In contrast, it did not affect the growth of murine L1210 cells and FS-4 normal human diploid fibroblasts. The hybridoma-derived 160 suppressor factor was selected to investigate its effect on cell-mediated cytotoxicity. The 160 suppressor factor did not inhibit natural killer cytotoxicity or its augmentation by interferon alpha or interleukin 2 or the generation of lymphokine-activated killer cells. However, this factor partially inhibited the generation of specific T cell-mediated cytotoxicity. PMID- 1873507 TI - Apparent stereoselectivity in propafenone uptake by human and rat erythrocytes. AB - The distribution of propafenone (PPF) enantiomers between the plasma and red blood cells (RBCs) was investigated using human and rat blood. In separate experiments, effects of incubation time (15-60 min), blood concentration (100 5000 ng ml-1), and plasma proteins on the RBC uptake of the enantiomers were studied. In both humans and rats, the distribution of propafenone enantiomers into RBCs was rapid, extensive, and stereoselective. However, the extent of RBC uptake and the direction of stereoselectivity were different in these two species. In humans, preferential distribution of (-)-PPF into RBCs resulted in lower plasma concentrations for this enantiomer, whereas in rat plasma, (-)-PPF was the dominant enantiomer. When the plasma was replaced with buffer, the stereoselectivity in the RBC uptake of the enantiomers was abolished. This suggested that stereoselective protein binding may be responsible for this phenomenon. A direct measurement of the extent of binding of PPF enantiomers to rat and human plasma proteins further confirmed this. Moreover, the distribution of the enantiomers in RBCs was not affected by low temperatures or addition of ouabain, suggesting passive diffusion as the underlying mechanism. These results suggest that stereoselective red blood cell uptake may be responsible, at least in part, for the differences in the plasma pharmacokinetics of PPF enantiomers observed after the drug administration to humans and rats. PMID- 1873508 TI - Effects of phenobarbital and 3-methylcholanthrene pretreatment on the pharmacokinetics and the pharmacodynamics of bumetanide in rats. AB - The effects of pretreatment with the enzyme inducers, phenobarbital (PB) and 3 methylcholanthrene (3-MC), on the pharmacokinetic and pharmacodynamic parameters of bumetanide were examined in rats. The nonrenal clearance (19.3 vs 29.6 ml min 1 per kg) of bumetanide increased significantly in PB treated rats. This suggested that the nonrenal metabolism of bumetanide is increased by pretreatment with PB, which was supported by significantly increased amounts of bumetanide glucuronide and desbutyl bumetanide excreted in 8-h urine, and reduced amounts of bumetanide remaining per gram of tissue after 30-min incubation of 100 micrograms of bumetanide with the 9000 xg supernatant fraction of liver, stomach, and kidney tissue homogenates in PB treated rats. The contents of hepatic cytochrome P-450 (1.29 vs 2.15 nmol mg-1 protein) and the weights of liver and stomach increased significantly in PB treated rats, suggesting that the metabolizing enzymes for bumetanide are induced by pretreatment with PB. The 8-h urine output per 100 g body weight was not significantly different by pretreatment with PB although the amounts of bumetanide excreted in 8-h urine increased significantly in PB treated rats. It could be explained by the fact that the dose of bumetanide used results in urinary concentrations at the plateau of the concentration-effect relationship. Therefore, the alteration in the urinary excretion rate of bumetanide by pretreatment with PB would not alter the diuretic effect. In 3-MC treated rats, pharmacokinetic and pharmacodynamic parameters were not significantly different and it suggested that the metabolizing enzymes for bumetanide are not induced by pretreatment with 3-MC although the contents of hepatic cytochrome P-450 and the weights of liver and stomach increased significantly by pretreatment with 3-MC. PMID- 1873509 TI - Utility of biplane transesophageal echocardiography in left ventricular wall motion analysis. AB - The biplane transesophageal echocardiography (BTEE) probe increases capabilities for scanning cardiac structures in cross-sectional and longitudinal planes. The present study was undertaken to determine if BTEE would enhance diagnosis of perioperative ischemia by identification of new segmental wall motion abnormalities (SWMAs), and the initial experience in 94 patients (37 intraoperative and 57 intensive care unit) is presented. The left ventricular wall motion at the midpapillary level was observed and recorded on 0.5-in videotape by both transverse and longitudinal scanning transducers. Using a cinememory loop, biplane images were replayed side by side, within minutes of their acquisition, and were compared and recorded for later off-line analysis by two independent observers. Intraoperatively, the images were obtained at various predetermined intervals, and in the intensive care unit one set of observations was made. In 20 patients, new SWMAs were observed: in 4 patients (20%), the SWMAs were observed only in the cross-sectional scanning, whereas in 7 patients (35%) they were observed only in the longitudinal scanning. In the remaining 9 patients (45%) the SWMAs were detected in both planes. Persistent diagnostic electrocardiographic changes of myocardial infarction and elevation of CK enzymes were observed in 6 of the 20 patients within 3 postoperative days. In conclusion, biplane imaging appears to be superior to the traditional single-plane imaging for evaluation of left ventricular function and myocardial ischemia. PMID- 1873510 TI - Comparison of tidal ventilation and high-frequency jet ventilation before and after cardiopulmonary bypass in dogs using two-dimensional transesophageal echocardiography. AB - This study compared the use of high-frequency jet ventilation (HFJV) and tidal ventilation (TV) in a group of dogs with induced global myocardial ischemia before and after cardiopulmonary bypass. Transesophageal echocardiography was used to determine whether HFJV with its lower airway pressures could improve cardiac performance. The surgical procedure was separated into four study periods: closed chest before bypass, open chest before bypass, open chest after bypass, and closed chest after bypass. During each of these study periods, the dogs were randomly ventilated with alternate periods of TV and HFJV to maintain the PaCO2 at 34.3 +/- 3.3 mm Hg (mean +/- SEM). Cardiac output, stroke volume, systemic mean blood pressure, left ventricular ejection fraction, left ventricular end-diastolic volume, left ventricular dP/dt, left ventricular stroke work, and expiratory volumetric flows were higher during HFJV, whereas airway pressures and pulmonary vascular resistance were lower. Increases in cardiac output and stroke volume during HFJV were due to a combination of improved left ventricular contractility indicated by increased LV dP/dt and increased left ventricular end-diastolic volume accompanying decreased airway pressures. These data indicate that HFJV with its lower airway pressure is associated with significantly less impairment of cardiovascular function than TV in dogs with induced global myocardial ischemia. PMID- 1873511 TI - Minimum pulse pressure and peripheral temperature needed for pulse oximetry during cardiac surgery with cardiopulmonary bypass. AB - The lowest values of pulse pressure (dPP) and peripheral temperature (Tp) associated with reliable readings from three different pulse oximeters (Biox Ohmeda 3700, Datex Satlite, and Nellcor N-200) were assessed, along with the ability of the pulse oximeters to work immediately before and after total cardiopulmonary bypass (CPB). The lowest mean dPP with a reliable O2 saturation reading was 13 mm Hg and the lowest mean Tp was 23.6 degrees C. The dPP needed for a reliable reading before total CPB did not differ significantly from that needed after total CPB. No significant differences in performance were found among the three oximeters during the study. PMID- 1873512 TI - Thiopental as an adjunct to hypothermia for EEG suppression in infants prior to circulatory arrest. AB - Fifteen infants were studied to evaluate the effect of profound hypothermia (16 degrees C to 18 degrees C) and hypothermia plus thiopental on the electroencephalogram (EEG) prior to circulatory arrest. Mean patient age and weight were 5.5 +/- 1.2 months and 4.9 +/- 0.3 kg, respectively. After core cooling on cardiopulmonary bypass (CPB), all patients received thiopental, 8 mg/kg, 5 minutes prior to circulatory arrest. Satisfactory EEG recordings were obtained for 9 patients, and serum thiopental concentration was measured in 12 patients. Hypothermia (mean venous return temperature, 17.8 degrees C +/- 1.6 degrees C) alone was associated with persistent cerebral electrical activity in 8 of 9 patients (89%). The addition of thiopental, 8 mg/kg, produced an isoelectric EEG in 6 of these 8 patients (75%). Mean circulatory arrest duration was 44 +/- 4 minutes. EEG activity resumed after reinstitution of CPB in all patients. Serum thiopental concentration at the end of CPB was negligible. It is concluded that hypothermia alone often may not produce EEG isoelectricity, and that the associated cerebral metabolic activity may be suppressed by adjunctive use of thiopental. PMID- 1873513 TI - Comparison of nicardipine and sodium nitroprusside in the treatment of paroxysmal hypertension following aortocoronary bypass surgery. AB - In an open, randomized, multicenter trial, intravenous nicardipine was compared with sodium nitroprusside in 74 patients with hypertension (mean arterial pressure [MAP] greater than or equal to 100 mm Hg) following coronary artery bypass surgery. Nicardipine was administered as a 2.5- to 12.5-mg bolus followed by a 2 to 4 mg/h infusion, and nitroprusside as a 0.5 to 6.0 micrograms/kg/min infusion. The aim was to reduce MAP to less than 90 mm Hg within 50 minutes and maintain it stable at 85 +/- 5 mm Hg. Nicardipine was effective in 35 of 38 patients (92%), and nitroprusside in 29 of 36 (81%) (NS). The decrease in MAP was not statistically different, but time until reaching the therapeutic end-point was shorter with nicardipine (P less than 0.01). Significant differences follow: increase in heart rate and decreases in mean pulmonary artery, right atrial, and pulmonary capillary wedge pressures were more marked with nitroprusside (P less than 0.01 and P less than 0.05, respectively), whereas elevation of cardiac index and depression of systemic vascular resistance were more marked with nicardipine (P less than 0.01 and P less than 0.05, respectively). Postreduction MAP was more stable with nicardipine, 51% +/- 24% of readings falling within the range 85 +/- 5 mm Hg versus 41% +/- 18% on nitroprusside (P = 0.058). Dose adjustment during the following 24 hours was less frequent with nicardipine, 1.1 +/- 1.6 versus 2.7 +/- 2.6 (P less than 0.01). Transfused blood volume was lower with nicardipine (924 +/- 644 mL) than nitroprusside (1,306 +/- 901 mL) (P = 0.08), despite similar postoperative blood losses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873514 TI - Continuous infusion of drugs: a simple and rational system. AB - Continuous infusion of potent, often short-acting drugs particularly affecting the cardiovascular system is becoming more common in the operating room and intensive care unit. Accuracy and, hence, safety are always important in drug therapy, and never more so than when using the potent vasoactive and cardioactive drugs, yet the multiplicity of methods for preparing these drugs for infusion creates a situation in which mistakes may easily occur. A series of decimally related dilutions for drug preparation is presented, which has been in use for the past 5 years in the cardiac intensive care units at this hospital. It is believed that this system is easy to understand and remember and it thereby simplifies the process. This system may enhance the accuracy of dosage and improve the safety for patients. PMID- 1873515 TI - Continuous blood gas monitoring with an intraarterial optode during one-lung anesthesia. PMID- 1873516 TI - Congenital cystic adenomatoid malformation of the lung in combination with a pulmonary sequestration. PMID- 1873517 TI - Intraoperative transesophageal echocardiography in blunt thoracic trauma. PMID- 1873519 TI - Case 4--1991. A 57-year-old man requires complex management for surgery on a dissecting thoracic aortic aneurysm. PMID- 1873518 TI - Pulmonary hemorrhage during cardiac surgery. PMID- 1873520 TI - Optimal pressures and flows during cardiopulmonary bypass. Pro: a low-flow, low pressure technique is acceptable. PMID- 1873521 TI - Optimal pressures and flows during cardiopulmonary bypass. Con: pressure is more important than flow. PMID- 1873522 TI - Mechanical and biological cardiac assist devices. PMID- 1873523 TI - A new laryngoscopy blade to facilitate double-lumen tube placement. PMID- 1873524 TI - Mixed venous oximetry. PMID- 1873525 TI - Pitfalls in the calculation of SVRI. PMID- 1873526 TI - A survey of the necessity of the hospitalization day in an Italian teaching hospital. AB - To assess the extent of inappropriate hospital use in an adult in-patients population we used a modified version of the Appropriateness Evaluation Protocol (A.E.P.) to evaluate retrospectively a cross-section of 273 patient-days in a large teaching hospital in the Greater Milan area. Overall, 41% were judged to represent inappropriate hospital use on the basis of the protocol's criteria. The rate of inappropriate hospital use was significantly associated with admitting specialty, ranging from 12% for surgery, to 20% for cardiology and to about 60% in psychiatric, geriatrics and neurology departments (p less than 0.01). Hospital days of patients with longer stays were more frequently inappropriate: a statistically significant trend of inappropriateness emerged ranging from 30% among patients with total length of stay (LOS) of 1-10 days to 60% among those with LOS greater than 30 days (p less than 0.01). This study confirms that there is a substantial rate of unnecessary use of hospitals but that such inappropriateness does not seem in most cases to be easily modifiable through "simple" organizational changes. PMID- 1873527 TI - Communication problems between doctors and nurses. AB - Communication difficulties between hospital doctors and nurses are well documented. A survey undertaken jointly by medical and nursing administration at Sir Charles Gairdner Hospital in Perth, Western Australia, verified difficulties in doctor-nurse communication as perceived by doctors and nurses, as well as by ward clerks as impartial observers. Questionnaire responses revealed some impediments in the flow of communication. Both nurses and doctors perceived less frequency of difficulties in communicating with members of their own professional group than with members of the other group. Nurses with university preparation and other special clinical qualifications perceived significantly fewer communication problems with doctors than nurses with less education. Interns perceived greater frequency in difficulty communicating with nurses than did more highly qualified doctors, and female doctors who were not interns claimed fewer problems than their male counterparts. Moreover, more highly qualified male doctors who had a previous occupation acknowledged fewer doctor-nurse communication problems. PMID- 1873528 TI - Malpractice. AB - The problem of malpractice suits and patient complaints is frequently mentioned in discussions concerning the quality of health care. The present paper reviews the following aspects of this problem: the magnitude of the problem, the categories of cases, insurance and legal aspects, effects on medical practice, institutionalized possibilities for solving conflicts, an answer to the question of why patients complain and sue, and risk management. PMID- 1873529 TI - A Patient Satisfaction Questionnaire as a teaching and comparative audit tool. AB - This paper explores the development and use of a Patient Satisfaction Questionnaire which was chosen by members of the South Australian Quality Assurance Research Officers' Association (SAQAROA) as a method of learning how to undertake quality assurance. Overall this process was rated as being successful by the members. Use of the Questionnaire revealed high overall satisfaction with services being provided. However, for most questions one or more hospitals returned comparatively high dissatisfaction rates, the significance of which was not appreciated until comparative data became available. PMID- 1873530 TI - High consumers of health care in emergency units: how to improve their quality of care. AB - Patients with non-urgent complaints and/or who attend frequently account for a substantial portion of the visits to emergency units. These patients usually require other types of care than that provided by a highly specialized emergency department (ED). In this paper we describe the development of ED utilization in the catchment area of Huddinge University Hospital, and the attempts made to improve the quality of care for high consumers of ED care. In a trial, nurse's advice and referral proved to be a feasible means of referring patients with non urgent complaints from the hospital emergency department to more appropriate care sources, such as primary health care centres. A long-term follow-up showed that without any intervention, frequent ED users are a high-risk group as regards morbidity and mortality, especially with respect to suicide. Prevention with comprehensive and continuous treatment programmes should therefore be planned when a tendency is noted for patients to attend the ED frequently. PMID- 1873531 TI - Studies in utilization of drugs: a review of different methods. AB - Pharmaceutical expenses are 19% of social security expenses in Spain. Studies of prescription habits, prescription prevalence, therapeutic profiles, prescription compliance and incidence reports are thus required. Different methods to study utilization of drugs are discussed and examples of each method are provided. The number of registered pharmaceutical specialties varies between 21000 in Germany (2900 active substances) and 1000 (700) in Iceland. The thiazide consumption varies between 4.3 daily defined doses (DDD) per 1000 inhab./day in Spain and 42.9 in Sweden. Medication errors were caused by recording problems in 6.5% of all drug distributions. PMID- 1873532 TI - Administration of pentamidine aerosol therapy. PMID- 1873533 TI - AIDS-related knowledge, attitudes, and behaviors among 629 registered nurses at a Minnesota hospital: a descriptive study. AB - Since nurses play a pivotal role in many aspects of healthcare delivery, their knowledge, attitudes, and behavior in relation to AIDS are crucial. A descriptive study was done to discover the AIDS-related knowledge, attitudes, and behavior among registered nurses who practice in a hospital setting, and to describe the relationship of these findings with other variables. A 67-item survey was sent to 704 registered nurses at a 455-bed acute care teaching hospital and its associated clinics. The results indicated there is a considerable level of misinformation, mistrust, and fear regarding AIDS among RNs practicing in the hospital setting. PMID- 1873534 TI - Examining the ethical and legal issues generated by the HIV epidemic. AB - This article addresses ethical and legal issues related to the HIV epidemic. The author discusses individual and utilitarian schools of philosophy, and identifies philosophical issues in relationship to the stage of HIV infection that the client is experiencing. Prevention strategies and nursing interventions for three levels of prevention are also presented. HIV infection is now accepted as a chronic disease, which is characterized by different stages. Nursing intervention focused on prevention can be related to the stage of infection. PMID- 1873536 TI - Fear of contagion among home health aides: a community survey. AB - Fear of contagion--an overwhelming anxiety about catching a disease--has been reported among a variety of healthcare workers as a common response to AIDS. This survey assessed the availability of home health aides to meet the predicted increases in demand for home health care to persons living with AIDS. The findings showed 27 out of 31 home healthcare agencies either experienced or anticipated experiencing difficulty servicing home care to persons with HIV infection. The author briefly discusses the dynamics of fear of contagion and offers specific suggestions for countering this fear among home health aides. PMID- 1873535 TI - It's time for new perspectives. PMID- 1873537 TI - Deciding when to leave patients with AIDS dementia complex alone. PMID- 1873538 TI - Occupational and personal risk estimates for HIV contagion among incoming graduate nursing students. AB - In an effort to measure both fear of HIV/AIDS contagion and possible co-factors, two cohorts (n = 331) of incoming graduate level nursing students were surveyed during two consecutive academic years. All completed a Risk Perception Scale and an AIDS Attitude Scale; additionally, 118 completed an AIDS Knowledge Scale. Findings indicate this population had tremendous fears of the possibility of HIV infection. Estimates of potential contagion far outweighed scientific estimates of risk, and in some cases corresponded to behaviors that are scientifically purported to have no risk. Of interest in this same regard were perceptions of increased risk in the case of visible testimony to disease (that is, in the case of holding a patient with Kaposi's sarcoma lesions versus one without) and in the case of a patient with AIDS (versus an HIV seropositive, asymptomatic patient). Results showed that exaggerated perceptions of risk were correlated with a lack of knowledge and with negative HIV-related attitudes. The study indicates the need for AIDS education that addresses biomedical findings and fact while concurrently addressing perceptions that may preclude the assimilation and application of such knowledge. PMID- 1873539 TI - Root submersion: a technique for function and aesthetics. PMID- 1873540 TI - A conservative alternative to single tooth replacement. PMID- 1873541 TI - Establishing proper anatomy in Class II posterior restorations. PMID- 1873543 TI - Breast cancer research and treatment. PMID- 1873542 TI - Combining natural teeth with implants; restoration of a mandibular arch with fixed prosthetics. PMID- 1873544 TI - Clinical features of breast cancer--Anglo-Japanese comparative study. AB - A comparative study was undertaken at Guy's Hospital in the UK and the Aichi Cancer Center in Japan of the clinical picture of breast cancer in the UK and Japan. Target patients were 221 UK and 200 Japanese primary operable patients who were recruited from April 1979 through August 1980. No difference was seen between the two countries in the side and site of the lesion and the size of the lesion. The localized tenderness of the tumor site was higher in Japanese patients than in UK patients (25.5% vs 0%). Difference was observed in tumor characteristics: breast cancers of the UK patients were irregular, ill-defined, and not so mobile, whereas those of the Japanese patients were round or oval, well-defined, and mobile. Skin fixation was higher in Japanese patients (71.0% vs 44.8%). Clinical node involvement was higher in UK patients (32.5% vs 19.0%). PMID- 1873545 TI - Early detection of breast cancer: mammography. AB - Detection of early breast cancer utilizing mammography can be accomplished through more frequent and earlier use of the test as well as exploring techniques to improve sensitivity and specificity. Efforts at educating primary care physicians about the role of mammography as well as training technologists and radiologists in performing optimum examinations and correctly interpreting them is of prime importance. The use of computers may aid in increasing the sensitivity of the examinations and may also provide improved feature analysis for the radiologist, thus enhancing the separation of benign and malignant disease. New technologies also show promise to improve the accuracy of mammography. Direct digital mammography and digital enhancement of standard mammograms are actively being investigated. The use of MRI and specifically 31P spectroscopy shows initial promise to increase the specificity of mammography. Several clinical trials are also under way to assess a possible niche which fine needle aspiration biopsy (FNAB) may occupy in the quest for early breast cancer detection. Any future collaborative work between Japan and Western countries should take into account the potential of these new methods for improving the sensitivity and specificity of mammography. PMID- 1873547 TI - Patterns of recurrence in Western and Japanese women with breast cancer. AB - The patterns of relapse in Western women with breast cancer were compared with women from Japan. The results reported are based on a review of the literature. A significant difference between Japanese and Western women was seen with regard to relapse in bone, lung, and liver as assessed clinically. More Western women had bone metastases, but the incidence of pulmonary and liver metastases was higher in Japanese women. A significant difference between the races was also seen with regard to locoregional recurrence of disease, with Japanese women showing a higher incidence of relapse in the supraclavicular lymph nodes compared to Western women. Postmortem studies showed that although the initial metastatic pattern may differ between Japanese and Western women, at time of death the disease is as widely disseminated in the former as it is in the latter. PMID- 1873546 TI - The international variation in breast cancer rates: an epidemiological assessment. AB - Part of the international differences in breast cancer incidence rates can be explained by geographic variation in reproductive and other breast cancer risk factors. Age at menarche and age at onset of regular ovulatory menstrual cycles are two such factors; both vary across populations directly according to breast cancer risk, and both are acknowledged as breast cancer risk factors. Consideration of the body of evidence on these factors, as well as that on age at menopause, suggests that the cumulative frequency of ovulatory menstrual cycles is a critical determinant of breast cancer risk. Although age at first term pregnancy explains the majority of the protective effect of parity on breast cancer risk, two recent studies have demonstrated a small residual protective effect of increasing number of births. It appears that pregnancy has paradoxical effects on breast cancer risk in terms of hormone production and metabolism. The initial effect is an increased risk associated with first trimester estrogen exposure. However, the hormonal consequences of completing the pregnancy counteract this negative effect of early pregnancy. The effect of body weight, a breast cancer risk factor for postmenopausal women, can be explained in terms of increased extraglandular conversion of androstenedione to estrone. Further evidence supporting a pathogenic role of estrogens in the development of breast cancer comes from international studies of endogenous hormones in populations with differing risks of breast cancer. These risk factors have been incorporated into a mathematical model which is based on the concept that breast tissue ages according to hormonal (primarily estrogen) exposure; this model closely predicts the incidence rates throughout the world. PMID- 1873549 TI - Patterns of recurrence and relapse--Anglo-Japanese comparative study. AB - A prospective study was undertaken to compare the recurrent sites of breast cancer patients in Japan and the UK. The number of patients collected between April 1979 and August 1980 were 205 in the UK and 199 in Japan, of which those who had recurrence were 89 and 49 respectively. A comparison of the distribution of the first recurrence sites demonstrated that the Japanese patients had significantly higher rates of local recurrence in the supraclavicular fossa and distant metastasis to the lung than UK patients. When comparing the distribution of all recurrent sites seen in the study, Japanese patients showed a significantly higher incidence of metastasis to the supraclavicular fossa and the lung while the UK patients showed a significantly higher incidence of skin metastasis. Bone metastases were observed more often in Japanese patients and liver metastases in UK patients, but neither of the differences were statistically significant. PMID- 1873548 TI - Ethnic variation in breast cancer survival: a review. AB - Intercountry, as well as intracountry, survival comparisons have revealed some differences in breast cancer survival among various ethnic populations. Most of these differences are probably explained by factors related to socioeconomic status. However, the well documented survival advantage of Japanese patients compared to Caucasian patients remains unexplained. Some recent studies suggest an adverse prognostic effect for obesity. Although still inconclusive, these findings raise the possibility that the better survival of Japanese patients may be in part related to their lower mean body weight. An effect of the lower fat intake of the Japanese in explaining their breast cancer survival advantage has little support at present, but, like the obesity hypothesis, deserves further study. PMID- 1873550 TI - Recurrence and survival rates in British and Japanese women with breast cancer. AB - The biology of breast cancer in Japan appears to be changing in that, while post menopausal Japanese patients have a better prognosis than comparable British women, no differences in recurrence or survival rates can now be found in pre menopausal patients. PMID- 1873551 TI - The effect of dietary fat on breast cancer survival among Caucasian and japanese women in Hawaii. AB - 182 Japanese and 161 Caucasian breast cancer patients participated in an epidemiologic case-control study from 1975-1980. They were subsequently followed until the end of 1987 to determine their survival status. Among the Japanese, patients with regional or distant disease had a relative risk (RR) of death of 13.0 (95% Confidence Interval (CI), 4.3-39.1) compared to those with in situ or localized disease, and obese patients had a RR of death of 3.5 (95% CI, 1.3-10.0) compared to non-obese subjects. Among the Caucasians, patients with advanced disease had a RR of death of 4.3 (95% CI, 1.8-10.5) compared to those with in situ or localized disease, and patients with a high fat intake had a RR of 3.2 (95% CI, 1.2-8.6) compared to subjects with a low fat intake. Menopausal status (pre- or postmenopausal) and replacement estrogen use were not related to survival from breast cancer in either ethnic group. When Japanese and Caucasian patients were compared with each other, there was no significant difference in survival between them. PMID- 1873552 TI - A comparison of epidemiological characteristics in breast cancer patients and normal women in Great Britain and Japan: results of a prospective study. AB - The epidemiological characteristics of normal women and women with early breast cancer in Great Britain were prospectively compared with similar subjects from Japan. The study consisted of 204 women with early breast cancer and 792 normal controls from Great Britain and 200 breast cancers and 335 Japanese controls. The risk factors examined were age, height and weight, menopausal status, age at menarche and menopause, parity, age at first birth, use of oral contraceptives, and family history of breast cancer. The cancers and cases were divided into pre- and postmenopausal groups. There was a striking trend for a protective effect of multiparity in both countries and a weak but inconstant protective effect of age at first birth. In premenopausal British women increase in body mass was significantly associated with a decreased risk of breast cancer but this association was not found for postmenopausal women or in the Japanese women. The results showed that the classical risk factors did not fully account for the differences in breast cancer risk between Great Britain and Japan. The possibility that aetiological factors might be changing warrants investigation. PMID- 1873553 TI - Endogenous hormones and breast cancer: a prospective cohort study. AB - A cohort study is under way in New York City to evaluate how levels of endogenous reproductive hormones influence the risk of breast cancer. The study, in which approximately 15,000 women are being recruited, utilizes a prospective design in which volunteers are asked to provide repeated specimens of serum during the period 1985-1992. A case-control study nested within the cohort is planned by which specimens from all cases arising in the population and from a randomly selected sample of time-matched controls will be analyzed and compared. As of December 31, 1989, 13,609 volunteers had donated blood specimens, about 50% of whom had already donated more than once. Of the 187 incident breast cancer cases who are expected to arise in the cohort before the end of 1992, 77 have been detected thus far. PMID- 1873554 TI - Genesis of breast cancer in Japanese: a possible relationship between sex hormone binding globulin (SHBG) and serum lipid components. AB - We investigated changes in the amount of sex hormone binding globulin (SHBG) and the percentage of free estradiol (% FE2) during normal menstrual cycles in the sera of 8 young Japanese controls, and also the relation between the lipid components of serum and the serum level of SHBG in 250 normal Japanese controls aged 18-77 years. The amount of SHBG measured by IRMA was significantly higher in the luteal phase than in the follicular phase, whereas the % FE2 values remained constant throughout the menstrual cycle in 8 healthy young controls. These results suggest that the estrogen status in serum is constantly controlled by SHBG. The amount of SHBG was significantly correlated with the serum level of triglycerides (TG) in 250 normal Japanese controls. From these results, we postulate that the decrease in serum SHBG, probably caused by increased level of serum TG, leads to elevation of % FE2 and later to a status with a high risk of breast cancer. PMID- 1873555 TI - Geographical variation in endocrine function and its relation to breast cancer incidence: some general considerations. AB - Abnormalities in endocrine function are not a determinant of risk of breast cancer within countries, and racial differences in this function do not explain geographical variation in risk. It is suggested that hormonal status is related to tumor growth rates and hence to age at diagnosis, recurrence rates after primary treatment, and survival. Such evidence as there is points in this direction, but it still remains to be finally established whether the disease runs a similar course in all countries when patients are standardised for factors known to affect prognosis. PMID- 1873556 TI - Serum hormone levels in British and rural Chinese females. AB - The comparison of blood levels of oestradiol, testosterone, prolactin, and sex hormone binding globulin (SHBG) was made of 3250 rural Chinese and 300 British women, aged 35 to 64. To reduce the number of assays performed the blood samples were combined so as to form 390 and 30 pools, respectively. The Chinese had significantly less oestradiol and testosterone. Prolactin levels were similar in both races. SHBG was significantly lower in postmenopausal British women. In the Chinese women, testosterone was positively and prolactin negatively correlated with breast cancer mortality. PMID- 1873557 TI - Blood concentrations of estradiol and sex hormone-binding globulin in relation to age at menarche in premenopausal British and Japanese women. AB - In a cross-sectional study, serum estradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were not significantly related to age at menarche in premenopausal British women in the luteal or follicular phases of the cycle. In Japanese subjects in the luteal phase, a marginally higher concentration of E2 was observed in those who had undergone an early rather than a late menarche. In British women, previous oral contraceptive users had significantly lower luteal phase E2 concentrations than never users. PMID- 1873558 TI - Breast cancer in multi-ethnic populations: the Hawaii perspective. AB - The five major ethnic groups in Hawaii's population of 1.1 million are the Japanese, comprising 23%; Caucasians, 23%; ethnic Hawaiians, 19.9%; Filipinos, 11.3%; and Chinese, 4.8%. Only 14% of the population is foreign born. Breast cancer incidences are 29.2 per 100,000 among Filipinos, 51.3 for Japanese, 64.1 for Chinese, 104.3 for Hawaiian, and 105.6 for Caucasian women. The Caucasian incidence is similar to mainland US rates, but the incidence among Hawaii's Japanese is more than twice the rate in Japan. Japanese in Hawaii have less postmenopausal breast cancer than Caucasians, fewer axillary lymph node metastases, and a greater proportion of non-invasive tumors. Late stage at diagnosis is common among Filipino and ethnic Hawaiian woman, and their risk of death is 1.5-1.7 times that of Caucasian, Chinese, and Japanese women with the disease, even after adjustment for age, extent of disease, and socio-economic status. In the BCDDP screening study, only 20% of breast cancers detected in ethnic Hawaiians were not yet palpable and were found by mammography alone. Comparative studies of diet and estrogen levels in the ethnic groups of Hawaii and the parental populations in Japan and the West do not account for the degree of variation observed in breast cancer incidence and tumor pathology. Future research directions are suggested with a view to accounting for these differences. PMID- 1873559 TI - Molecular and cellular lesions associated with breast cancer progression. AB - Breast cancer may be more than one disease with differing etiologies. At the molecular level, breast cancer may be the result of a complex, dynamic, and stochastic process where there is more than one way to accomplish each of the steps necessary for malignant growth. The well documented biologic heterogeneity of breast cancers may arise from the many possible molecular changes that can accomplish a given step with variable efficiency. Alternatively, this heterogeneity may also reflect various possible orders of acquiring the sum of steps necessary for malignant growth. We have attempted to describe some of the molecular changes associated with breast cancer in the context of this broad conceptual framework. We have found that the capacity for infinite growth in culture usually occurs at a late stage of malignant progression and is frequently associated with activating ras mutations. Loss of heterozygosity at chromosome 11p can occur either early or late in progression, while losses at chromosome loci 1q and 17p, although independent of each other, are found in primary breast cancers. Whether the same molecular and cellular changes are to be found in Japanese patients remains to be determined. PMID- 1873560 TI - The pathology of breast cancer in Japanese women compared to other ethnic groups: a review. AB - Review of comparative pathology studies of breast cancer among Japanese women and other ethnic groups reveals consistent differences in tumor morphology and host response. Japanese women show lower rates of breast cancer than Caucasian women, a difference that is accounted for by increased rates of this cancer in postmenopausal Caucasian women. Postmenopausal breast cancer is also less common among Japanese who migrated to a western environment. Autopsy studies of Japanese women without breast cancer indicate a lower prevalence of ductal hyperplasia, a breast cancer precursor, among indigenous Japanese women and first generation migrants than among second generation Japanese women in Hawaii who have higher rates of breast cancer. Postmenopausal breast cancers in Caucasian women are more likely to have estrogen receptors than cancers in postmenopausal Japanese women or premenopausal women of either race. Postmenopausal Japanese women are more likely to have in situ tumors than Caucasian women, even after adjusting for tumor size. A more vigorous host response to breast cancer among Japanese women, as compared to Caucasians, is suggested by more intense lymphocytic infiltration, greater degrees of lymph node sinus histiocytosis and fewer lymph node metastases in the Japanese. PMID- 1873561 TI - Breast cancer in English and Japanese women: prognostic significance of sinus histiocytosis and germinal center hyperplasia in axillary lymph nodes. AB - A prospective study of comparable Japanese and British breast cancer patients treated by radical mastectomy confirmed previously reported findings that sinus histiocytosis and germinal center hyperplasia are more frequently seen in axillary lymph nodes from Japanese than in those from British patients. In Japanese, but not British, cases of either of these two morphologic findings had favorable prognostic significance for recurrence. Sinus histiocytosis also had favorable prognostic significance in Japanese cases for five year survival. In a separate review of axillary nodes from Japanese autopsy cases sinus histiocytosis was absent, suggesting that this finding in Japanese breast cancer cases was related to presence of the disease. PMID- 1873563 TI - Pathology of breast cancer: present and prospect in Japan. AB - Breast cancer among Japanese females is characterized by its relatively low incidence and better prognosis than among Caucasian females. The annual mortality due to breast cancer among Japanese is about one-fifth that among Caucasians. Comparison of case distribution by histological type indicates that the ratio of well-differentiated carcinoma is slightly higher among Japanese, while the ratio of poorly differentiated carcinoma is slightly higher among Caucasian females. It is noteworthy that the incidence of in situ and invasive lobular carcinoma among Japanese is much lower than among Caucasian females. The age distribution shows that breast cancer is more frequent among middle-aged females in Japan, but more common among aged females in the West. Breast cancer among Japanese females shows a better prognosis than among Caucasian females as a whole, even with equal tumor size and lymph node metastasis. As mentioned above, the morbidity and mortality rates of breast cancer among Japanese females are very low, but recently, both morbidity and mortality rates in Japan have been steeply increasing. For example, the mortality rate of breast cancer in Japan almost doubled during the past 20 years. Moreover, biological behavior of breast cancer among Japanese females has been recently changing. Time-trend data clearly indicate that breast cancer in Japan in the future will be much more like that in the West, and nowadays it is already westernizing. PMID- 1873562 TI - Comparative histological analysis of British and Japanese breast carcinomas. AB - Histopathological analysis of several factors was made in an attempt to explain the difference in prognosis after mastectomy for mammary carcinoma in Japanese and British women. The higher age, lower grade of differentiation, and lower sinus histiocytosis and germinal center hyperplasia of the British cases may explain their worse prognosis. PMID- 1873564 TI - Breast cancer screening. A brief historical review. AB - Breast cancer screening by a combination of clinical breast examination (CBE) and mammography is effective in reducing mortality from breast cancer in all age groups for years 40 and above. Mammography is the single most effective method in obtaining the mortality reductions. The CBE should not be omitted, however, in that it does add information not apparent on mammography. The CBE can be done safely by a nonphysician properly trained. Breast self-examination (BSE) is ineffectual in reducing mortality. It is debatable if it has a role in screening for breast cancer at all. This observer believes it should be done, in that its cost is minimal once the training is over. PMID- 1873565 TI - A comparison of mammographic parenchymal patterns in premenopausal Japanese and British women. AB - Normal premenopausal Japanese women have significantly more favourable mammographic parenchymal patterns (Wolfe Grades) than comparable British women. This finding is unaffected when the women are stratified by age, Quetelet's Index, age at menarche, age at first birth, and parity. PMID- 1873566 TI - Estimating the sensitivity of breast cancer screening--experience with the Honolulu BCDDP data. AB - The 'capture-recapture' models for estimating breast cancer screening sensitivity can be generalized to include factors that affect sensitivity such as cancer size. Including such factors can help reduce the covariance between mammographic and physical exam sensitivity, which will improve the estimates. One model relating sensitivity to cancer length is presented and tested using data from the Honolulu Breast Cancer Detection Demonstration Project (BCDDP). The model predicts sensitivity fairly well for large breast cancers, but underestimates sensitivity for small cancers. Using both mammography and physical examination, the total screening sensitivity is estimated as 0.91 +/- 0.03 for cancers longer than 12 mm (for the second through fifth screenings for Honolulu and Tucson screening data combined). Limited data suggest similar screening sensitivities for Orientals and Caucasians in Hawaii. Shortcomings of the BCDDP data include inaccurate measurements of cancer length. Suggestions to improve data for future work are given. PMID- 1873567 TI - Understanding due discretion of judgment in Catholic marriage courts. AB - Psychiatrists and psychologists provide consultation to the Catholic Church's marriage courts. Operating under the Church's legal code, these tribunals assess the validity of weddings that have ended in divorce. This report describes one of the standards used for this purpose, the lack of due discretion of judgment, which is concerned with the maturity, understanding, and appreciation that the couple brought to the ceremony. This normal capacity is vulnerable to various mental illnesses, which if present with sufficient severity may nullify the marriage vows as seen by the Church (though not necessarily by the state). Such a finding results in freedom to marry again despite the Church's ban on divorce, provided that due discretion of judgment is regained. Case examples and discussion of the assessment process for due discretion of judgment prepare the consultant to apply psychiatric findings to this unique and urgent legal issue. PMID- 1873568 TI - Unconscious fantasies: from the couch to the court. AB - No single unifying theory exists that explains the plethora of behaviors that bring individuals before the courts on a daily basis. No biological, social, or familial model for criminal behavior is without limitations, or exempt from controversy and criticism. We suggest, however, that it is appropriate, and often necessary, for the psychiatric expert to advance lucid, intelligible, and simplified psychodynamic formulation, either alone or in conjunction with another explanatory model of criminal behavior, to assist the court in its understanding and disposition of a given case. In some cases, apparent criminal behaviors result when unconscious motivating factors, particularly unconscious fantasies, find expression in conscious life. In this article, we consider the etiologic role of unconscious fantasy in certain seemingly inexplicable criminal behaviors. The concept of unconscious fantasy is explained and a detailed case description and formulation are provided in order to illustrate the central role of unconscious fantasy in some of these behaviors. Recommendations are offered for the manner in which psychodynamic formulation should be presented in reports and in courtroom testimony through reference to the author's experience. PMID- 1873569 TI - Morality and pretextuality, psychiatry and law: of "ordinary common sense," heuristic reasoning, and cognitive dissonance. AB - The thesis of this paper is that we will not make significant progress in understanding the tensions between the legal and mental health systems until we look carefully at a series of dissonances that affect both systems. We must consider the way that the law frequently condones pretextuality as a way of dealing with troubling or cognitively dissonant information, and the way that mental health professionals encourage a self-referential concept of morality as a way of subverting legal doctrines with which they disagree. These dissonances must be considered contextually in connection with the ways that courts generally read social science data and the ways that jurors and legislators employ such cognitive devices as "ordinary common sense" and heuristic reasoning in their judgments of cases involving mental disability questions. To ameliorate the current dilemma, we must redefine institutional and professional roles, reconsider the way we privilege expertise, recalibrate our allocation of "moral jurisdiction" over these matters, and consciously confront the way our simplifying thinking mechanisms distort the underlying social and political issues. PMID- 1873570 TI - Is money a cure? Follow-up of litigants in England. AB - American and British authors collaborated on a follow-up study in England of accident victims who brought litigation which had been resolved. Eighteen subjects who had complained of psychiatric symptoms during the course of the litigation were recruited from the British psychiatrist's files. Based on review of court documents and extensive interviews of the subjects, the authors describe case examples that demonstrate a complicated relationship between monetary compensation and outcome. Some of the litigants improved after they received compensation, but this seemed to be related to issues besides the money, e.g., feelings about their impairment, family support, the loss or gain of a relationship, personality characteristics, and ability to return to work. The authors discuss the results of this study in light of differences between the British and American legal systems. PMID- 1873571 TI - A controlled comparison of involuntarily hospitalized medication refusers and acceptors. AB - Involuntarily hospitalized psychiatric patients consecutively admitted over a six month period who successfully refused medication (n = 37) are compared with a randomly selected group of medication-accepting patients committed during the same time period (n = 37). The overall refusal rate was 15.6 percent during the study period. Acceptors and refusers did not differ on age, sex, diagnosis, ethnicity, marital status, or preadmission living status. Differences between the groups indicate that refusers are sicker and lower functioning, are more behaviorally acute on the ward, and stay in the hospital twice as long as acceptors. Refusers also have a significantly negative impact on the overall ward milieu. The impact of institutional factors on the rate and outcome from mediation refusal are discussed. PMID- 1873572 TI - Antisocial burnout: an exploratory study. AB - The more flagrant aspects of Antisocial Personality Disorder (APD), particularly criminality, are thought to diminish or "burnout" after age 30. However, empirical evidence of burnout in clinically defined groups is lacking. This study explores burnout in a cohort of forensic psychiatric patients, aged 41 to 67, with clinically diagnosed DSM-III APD (N = 39). Conviction data revealed that criminality did appear to decline from age 27 onward, but not in a straightforward manner. Further, a significant portion of the cohort remained criminally active throughout most of their adult lives. Age did not appear to interact with crime class. PMID- 1873573 TI - Type of symptomatology as a form of volunteer bias. AB - We sought to explore the relationship between type of psychopathology and consent bias. Using the Brief Psychiatric Rating Scale we assessed a group of 48 forensic psychiatric inpatients. These patients were later independently approached by a researcher who attempted to get their consent for a study on the validity of self reported criminal behavior. Thirty agreed to participate and 18 did not. The consenting patients were significantly younger and had significantly more negative symptoms than the nonconsenters. The difference in negative symptoms remained significant after age and medication dose, in chlorpromazine equivalents, were covaried out. The authors discuss the implications of these findings for forensic research. PMID- 1873574 TI - The military insanity defense. AB - This article describes the military insanity defense. The success of the litigated insanity defense is explored through the number of insanity acquittals over a 28-month period. A questionnaire distributed to all United States Army psychiatrists provided information on the number of forensic evaluations performed, the number of not criminally responsible (NCR) opinions made, and the disposition of noncontested NCR opinions. The questionnaire also tested the Army psychiatrists' knowledge about recent changes in the military insanity defense. This pilot study raises interesting questions about the military insanity defense that further research can address. PMID- 1873575 TI - Crime and multiple personality disorder: a case history and discussion. AB - The application of the concept of multiple personality disorder (MPD) is one of the most complex and controversial issues facing forensic psychiatrists. The case presented is one in which a diagnosis of multiple personality disorder is not only well documented, but was so diagnosed at least 10 years before the ultimate homicide. Nonetheless, consideration of the legal issues was difficult. Other cases, particularly the Bianchi case, reflect the clinical difficulties in diagnosis. Subsequent cases have reflected a judicial review of the issues and a trend to disallow the concept of MPD as a defense; the author suggests that forensic psychiatrists incorporate these opinions in their future judgments. PMID- 1873576 TI - The Shakers and their proprietary medicines. PMID- 1873577 TI - "A disease sui generis": the origins of sickle cell anemia and the emergence of modern clinical research, 1904-1924. PMID- 1873578 TI - A profile of the medical profession in Scotland in the early twentieth century: the Medical Directory as a historical source. PMID- 1873579 TI - The Fielding H. Garrison lecture. Walter B. Cannon and the politics of medical science, 1920-1940. PMID- 1873580 TI - Texts and documents. The earliest-known account of Semmelweis's initiation of disinfection at Vienna's Allgemeines Krankenhaus. PMID- 1873581 TI - Paediatric cochlear implantation in the United Kingdom--a delayed journey on a well marked route. PMID- 1873582 TI - Tinnitus: evaluation of biofeedback and stomatognathic treatment. AB - Thirty-two patients with disabling tinnitus received stomatognathic treatment and biofeedback therapy according to a cross-over design. The evaluation of treatment outcomes showed some improvements at the group level: decrease of tinnitus intensity, mood improvement and reduction of clinical signs of dysfunction in the masticatory system. Qualitative observations indicated numerous positive changes in patients' emotional and cognitive orientation vis a vis tinnitus. Some possible predictors of positive treatment outcome were observed: comparatively low severity of tinnitus, normal hearing or compensated hearing loss, occlusal interferences, jaw fatigue, diurnal bruxism and fluctuations in tinnitus intensity. Left-sided tinnitus seemed to be a negative predictor of stomatognathic and biofeedback treatment outcome. Consequently, stomatognathic and biofeedback treatment seem to have some positive effects on subgroups of tinnitus patients. PMID- 1873583 TI - Perceptual consequence of vents in hearing aids. AB - The perceptual consequence of venting an earmould while maintaining the insertion gain at a preferred listening level was examined on nine hearing-impaired individuals with bilaterally symmetrical sloping sensorineural hearing loss. Subjects wore binaural programmable hearing aids and selected their preferred insertion gain while the hearing aids were coupled to vented (2.2 mm parallel vent) and unvented earmoulds. A modified Simplex procedure with discourse passages presented in quiet was used to determine preferred insertion gain. The results showed that venting enhanced subjects' quality rating of the hearing aids during listening and vocalization tasks, but did not change subjects' word recognition scores. These results suggest that vented earmoulds should be used to achieve target insertion gain in order to maximize patients' acceptance of hearing aids. PMID- 1873584 TI - Optimization of a slow-acting automatic gain control system for use in hearing aids. AB - This paper describes experiments evaluating and optimizing an automatic gain control system, called dual front-end AGC (abbreviated as D), intended for use in hearing aids. This system has two purposes: (1) to compensate for variations in the overall level of speech from one situation to another by slowly changing its gain; (2) to protect the user from sudden intense transients without affecting the long-term gain. This is achieved by using two control voltages to determine the gain. One changes slowly as the input varies in level. Normally this component determines the overall gain. The other comes into operation when an intense transient occurs. It acts rapidly to reduce the gain, avoiding over amplification of the transient, but its action ceases quickly after the end of the transient. We describe four experiments measuring speech intelligibility for subjects with cochlear hearing loss in which we determine optimum values for two of the time constants of the D system, namely the recovery time of the fast component and the attack time of the slow component. The experiments also compare the D system with linear amplification (L) and 'adaptive compression' (A). The results show: (1) for the D system, optimum values are about 80-150 ms for the recovery time of the fast component and 150-325 ms for the attack time of the slow component; (2) in situations where intense transient sounds are present, and there is either no background sound (experiment 1) or continuous speech-shaped noise as a background (experiment 2), the D system gives significantly better performance than the L or A systems. When the background noise is a single voice, reversed in time (experiment 3), the D and L systems give similar performance, and both are markedly superior to the A system; (3) when the level of speech is varied over a range of 30 dB (experiment 4), both D and A systems allow good performance over the whole range of levels. Performance for the L system worsens markedly at the lower levels. PMID- 1873585 TI - A comparison of the effects of different methods of impression build-up on earmoulds. AB - An investigation was carried out into effects of three types of impression build up (patting down of impressions, special earmould-maker build-up and the multistage impression technique) on the dimensions, static pressure seal, degree of acoustic seal and the subjective tightness and comfort of earmoulds. Patting down the impression significantly improved the degree of acoustic seal provided by earmoulds without making them feel tighter or less comfortable. However, special build-up was much more effective than patting down and the multistage impression technique was slightly more effective than special build-up in improving the degree of acoustic seal. The improvement in acoustic seal provided by both multistage and specially built-up earmoulds can usually be obtained without an unacceptable level of discomfort. Patting down the impression did not improve the chance of obtaining a static pressure seal. Special build-up of the impression by the earmould-maker significantly increased the proportion of earmoulds which provided a static pressure seal but an even higher proportion of earmoulds made from multistage impressions provided a seal. Dimension results indicated that an increase in earmould-maker build-up of the minor axis at the beginning of the canal segment of the impression would improve the acoustic seal provided by specially built-up earmoulds and that earmoulds with rounder tips are more likely to provide a static pressure seal than earmoulds with more elliptical tips. The better the impression material fills the ear canal, the rounder the tip of the impression, and the rounder the tip of the earmould made from the impression. PMID- 1873586 TI - A qualitative study of strategies for managing a hearing impairment. AB - The aim of this study was to gain a deeper understanding of what hearing-impaired people are doing to deal with demanding auditory situations in everyday life. Twelve middle-aged subjects with clinical hearing impairments were interviewed monthly during 5 months. The interviews focused on the subjects' own descriptions of demanding auditory situations and what they did, thought and felt in these situations. Verbatim transcribed protocols were content-analysed according to Grounded Theory. Fourteen categories were grounded in the data, forming a model for dealing with demanding auditory situations, including two qualitatively different management patterns: 'to control the social scene' and 'to avoid the social scene'. The emerging core variable was socio-psychological: the hearing impaired individuals strive to maintain the normal identity and to prevent their definition as deviant in interactions with hearing people. The result of the inductive study was verified in a deductive study of 50 hearing-impaired subjects. PMID- 1873587 TI - Streptococcal septicaemia following autologous bone marrow transplantation in children treated with high-dose chemotherapy. AB - A total of 251 patients were given 326 courses of high-dose chemotherapy followed by autologous bone marrow transplantation between February 1979 and August 1988. Ninety-one cases of septicaemia developed in 84 patients, 33 of these cases (36%) were due to streptococci. The outcome was fatal for four patients (12.1%). No specific risk factors were identified which might account for this septicaemia and no clinical feature was significantly associated with these cases of bacterial infection. Pulmonary and neurologic septic complications, however, were of very poor prognosis since all patients with these complications died. The high rate of streptococcal septicaemia and the poor outcome for patients with prolonged and profound neutropenia led us to modify our choice of initial broad spectrum antibiotic therapy. PMID- 1873588 TI - Serum erythropoietin levels in patients undergoing autologous bone marrow transplantation. AB - Serum erythropoietin (sEpo) levels were serially measured with a radioimmunoassay in 14 patients undergoing autologous bone marrow transplantation (BMT), starting before the institution of the conditioning regimen up to day +45. An increase in sEpo levels was observed soon after starting the chemotherapy regimen, and before an evident fall in hemoglobin (Hb) levels took place. The peak in sEPo levels (221 +/- 181 mU/ml) was reached at day 0 in 9/14 patients, and was delayed up to day + 10 in the remaining five. There was a negative correlation between loge sEpo and Hb values (r = -0.730; p less than 0.01); the regression line of this correlation was comparable to the one obtained in a group of 15 iron-deficiency anemic subjects. Therefore, patients undergoing autologous BMT appear to be able to develop adequately increased sEpo levels in response to the severity of anemia. No correlation was found between sEpo and white blood cell or platelet count. On the other hand, sEpo value at day 0 was significantly related to the day of neutrophil recovery (r = -0.806; p less than 0.001): patients with the highest sEpo levels at day 0 showed significantly faster (p less than 0.001) neutrophil recovery. PMID- 1873589 TI - The development of cataract in children as a late side-effect of bone marrow transplantation. AB - Children with hematological malignancies (n = 33), severe aplastic anemia (SAA, n = 7) and other non-malignant diseases (n = 4) were followed for cataract development after bone marrow transplantation (BMT). The children with hematological malignancies were subjected to total body irradiation (TBI), 10 Gy, in one session with no shielding of the eyes as part of their conditioning regimen before BMT. The children with SAA or other non-malignant diseases received either no irradiation before BMT or a reduced dose, 8 Gy, with shielding of their eyes. After 3 years all patients who had undergone BMT for hematological malignancies had developed lens opacification. No patients in the other groups, without leukemia, showed any sign of cataract development. There was no relationship between steroid treatment for graft-versus-host disease and cataract development. No relation to age of onset of treatment or to the sex of the patient and cataract formation was seen. It seems evident from the present study that TBI given in one session was the main cause of cataract development after BMT. PMID- 1873590 TI - Early herpes zoster infection in adult patients with Hodgkin's disease undergoing autologous bone marrow transplant. AB - The incidence of varicella-zoster-virus infection/reactivation in adult patients with Hodgkin's disease undergoing autologous bone marrow transplantation (BMT) at the University of Minnesota Hospital and Clinic was determined. Seven of 28 evaluable patients (25%) developed varicella-zoster infections in the first 150 days post-transplant. Two additional patients developed zoster after day 150 for a total incidence of 32%. We evaluated analysed risk factors to determine if there were any characteristics that could identify patients at risk for zoster early (less than 150 days) in their post-transplant course. Sex, age, prior radiation, and lack of immunity as determined by viral antibody titers were not associated with an increased incidence. Ten of the 28 patients had a history of zoster at some time after the diagnosis of Hodgkin's disease. Six of these 10 patients (60%) again developed zoster post-transplant. This compared to only one episode of varicella-zoster post-transplant among the 18 patients without a history of zoster following the diagnosis of Hodgkin's disease (p less than 0.01, Fisher's exact). We conclude that a prior history of zoster any time after diagnosis of Hodgkin's disease is strongly associated with developing zoster in the first 150 days after autologous BMT. PMID- 1873591 TI - Bone marrow transplantation from related donors other than HLA-identical siblings: effect of T cell depletion. AB - Results of 470 bone marrow transplants from related donors other than genotypically HLA-identical siblings (alternative related donors) were analysed to identify factors associated with transplant outcome and to determine whether T cell depletion improved results. As compared to 3648 transplant from HLA identical siblings, alternative related donor transplants were associated with increased graft failure, increased acute graft-versus-host disease (GVHD), and lower disease-free survival. The likelihood of adverse outcome correlated with increasing donor-recipient HLA-disparity. In multivariate analysis of alternative related donor transplants, donor age greater than or equal to 30 years, (relative risk [RR] 1.7, p less than 0.006), intermediate and advanced leukemia (RR 1.5 and 1.6, p less than 0.01 and p less than 0.003), infection pretransplant (RR 1.7, p less than 0.005) and 2- and 3-locus donor-recipient HLA-disparity (RR 1.3, p less than 0.04) were associated with increased risks of treatment failure. The 2-year probability of leukemia-free survival after alternative related donor transplants (n = 43) with none of these adverse prognostic features was 44% (95% confidence interval 28-59%) compared to 56% (95% confidence interval 52-59%) for similar patients receiving HLA-identical sibling transplants (n = 868, univariate p less than 0.03). T cell depletion increased graft failure and decreased acute GVHD after alternative related donor transplants but did not improve leukemia-free survival. PMID- 1873592 TI - Treatment of adult acute lymphoblastic leukemia with allogeneic bone marrow transplantation. Multivariate analysis of factors affecting acute graft-versus host disease, relapse, and relapse-free survival. AB - Between February 1972 and December 1987, 192 adults (greater than or equal to 18 years old) with acute lymphoblastic leukemia were transplanted using genotypically HLA-identical marrow donors. Median patient age was 23 years. Eighty-nine patients were in marrow remission and 103 were in relapse. Conditioning regimens included chemotherapy alone (three patients) or in combination with 9.2-17.5 Gy total body irradiation (189 patients). Graft-versus host disease (GVHD) prophylaxis consisted of methotrexate and/or cyclosporine. Seventy-nine patients developed grades II-IV acute GVHD and 28 of 122 patients who survived at least 100 days developed chronic GVHD. Relapse-free survival at 5 years was 21% for patients transplanted in first remission, 15% for those in greater than or equal to 2nd remission, and 12% for those transplanted in relapse. Patient and donor characteristics were evaluated in multivariate analyses for their effect on development of acute GVHD, survival, relapse, and relapse-free survival. An increased risk of developing acute GVHD was associated with increasing donor age. Variables significantly associated with both increased survival and relapse-free survival included transplantation in first remission, younger patient age, and not developing interstitial pneumonia. A decreased probability of relapse was associated with transplantation in first remission, male patient sex, and grades II-IV acute GVHD. PMID- 1873593 TI - Cyclosporine and methylprednisolone after allogeneic marrow transplantation: association between low cyclosporine concentration and risk of acute graft-versus host disease. AB - A combination of cyclosporine (CSA) and methylprednisolone (MP) was used as graft versus-host disease (GVHD) prophylaxis in 25 patients age 11-47 years (median 27 years) who received HLA-compatible sibling marrow transplants after myeloablative therapy for leukemia, myelodysplasia or lymphoma. CSA was initiated at 3 mg/kg/day in two divided doses, and the dose was adjusted to maintain a trough whole blood h.p.l.c. concentration between 200 and 800 ng/ml. While on i.v. CSA, the dose of CSA was increased for 10 of the 25 patients. The actuarial rate of grades II-IV acute GVHD was 37%. Those patients who developed moderate to severe GVHD had a significantly higher early mortality than those who did not (56% vs 12%, p = 0.02). There was a significant association between the development of acute GVHD and a mean week 2 CSA trough concentration less than 250 ng/ml. Life threatening regimen-related toxicities in the first 100 days included capillary leak syndrome, acute pancreatitis and small bowel perforation. Although the combination of CSA and MP in this dosing schedule was active in preventing acute GVHD, nephrotoxicity remained a problem, and outcome was limited by the inability to achieve the target CSA trough concentration in a substantial proportion of patients. PMID- 1873594 TI - Prothrombotic hemostatic abnormalities in patients with refractory malignant lymphoma presenting for autologous stem cell transplantation. AB - Forty-six patients with refractory malignant lymphoma (Hodgkin's and non Hodgkin's) admitted for autologous marrow or peripheral blood stem cell transplantation (ASCT) were evaluated for the presence of hemostatic abnormalities known to be associated with a hypercoagulable state in other patient populations. All patients had received numerous chemotherapeutic agents in the past and often radiation therapy as well. Hemostatic abnormalities were found to be common in these patients. The most frequent finding was hyperfibrinogenemia, present in 35% of patients. Decreased protein C activity was present in 32% of patients. Protein C antigen was low in only one individual and protein S was normal or increased in all patients. Low levels of antithrombin III were present in 16%. Plasminogen activator inhibitor was elevated in 20%. Anticardiolipin antibodies were present in 29% of patients; other evidence of a lupus anticoagulant was present in only eight patients. The frequency of each hemostatic abnormality was similar for patients with Hodgkin's disease (HD) and those with non-Hodgkin's lymphoma (NHL) despite the fact that significantly more patients with HD had received irradiation and/or previous splenectomy than patients with NHL. We conclude that multiple prothrombotic abnormalities of hemostasis are present in patients with refractory lymphoma referred for ASCT. Whether these are the result of lymphoma or the result of therapy cannot be determined from this study. PMID- 1873595 TI - Fat embolism syndrome following bone marrow harvesting. AB - A case of fat embolism syndrome is reported following an uncomplicated bone marrow harvest. The presenting symptoms were restlessness, shortness of breath and arterial hypoxemia. A lung perfusion scan ruled out the presence of a lung thromboembolism. The patient received supportive therapy and recovered within a few hours. We speculate that the larger gauge needle (13 vs 15) used to aspirate the bone marrow may have represented increased trauma to the iliac crest leading to fat embolism. PMID- 1873596 TI - Transient elevation of serum lactic dehydrogenase following autologous bone marrow transplantation. AB - Transient elevated levels of serum lactic dehydrogenase (LDH) were reported immediately following autologous bone marrow transplantation consecutively in 15 patients. Isoenzyme 2 was the predominant elevated isoenzyme of LDH, suggesting that the source of LDH is either hemolysis of RBCs, which occurs during freezing and thawing of bone marrow in the bags and in vivo following infusion of residual dimethyl sulfoxide. PMID- 1873597 TI - A commercially available culture medium compares favorably to laboratory medium (LM) for assay of peripheral blood colony forming units (CFU) PMID- 1873598 TI - Incidental correction of severe IgA deficiency by displacement bone marrow transplantation. PMID- 1873599 TI - The effectiveness of post-acute rehabilitation. PMID- 1873600 TI - Brain injury: analysis of outcome in a post-acute rehabilitation system. Part 1: General analysis. AB - During the past decade the rehabilitation field has developed new, non-hospital based programmes of cognitive, behavioural, social, educational and vocational treatments to address the higher order cognitive, behavioural and social deficits following brain injury. These new arrays of programmes are referred to under the term 'post-acute' rehabilitation. No comprehensive, methodologically sound study of the effects of these new treatments has been made to date. This paper reports data from brain-injured patients who underwent treatment within a co-ordinated system of post-acute brain-injury rehabilitation programmes. This system consists of a continuum of neurobehavioural, residential, day treatment and community and home programmes, and provides overt components of medical and rehabilitation care: behavioural management; activities of daily living, self-management, substance-abuse, social, academic and vocational skills training; counselling; and family education. The changes in function during the course of treatment by this post-acute sequence of rehabilitation have been obtained and are reported here. A defined total population of N = 192 is examined, with exclusions for appropriate causes (e.g. patients seen only for evaluation) producing a study population of N = 173; of these, follow-up was achieved in 145 cases, a follow-up rate of 83.8%. Time from date of injury to data of admission, severity of deficit at time of admission to programme, and other appropriate independent variables are used to characterize the population. A single-blind interview methodology was employed in obtaining dependent measures of outcome at 6, 12, or 24 month periods post-discharge. Measures of outcome included residential status, level of productivity activity and hours per day of attendant care or supervision required. Dependent variables were analysed for the total study population and a subgroup greater than 1 year from date of injury at entry to treatment and not from a treatment facility. Results are presented in terms of the percentage change in dependent measures from the point of admission to follow-up. Appropriate parametric and non-parametric statistical analyses of significance have been carried out. The results document substantial improvements in function during the post-acute rehabilitation of this population and such improvements are unlikely to be the result of spontaneous improvement alone. PMID- 1873601 TI - Outcomes of community re-entry programmes for brain injury survivors. Part 1: Independent living and productive activities. AB - This is a study of the multiple outcomes of residential community re-entry programmes for disabled survivors of brain injury. The sample consisted of 82 clients from nine facilities across the USA. The level of functioning of the client at and before admission was determined from clinical evaluations reported in programme records. Telephone interviews assessed outcomes 1 year after discharge. The participation in the re-entry programmes led to enduring improvements in independent living and productive activities. Total supervision requirements decreased substantially. Paid employment increased, but benefits went much beyond this to include improvements in educational activities, unpaid vocational activities, and especially household management. For the most part, these improvements cannot be attributed to chronicity or natural healing. The benefits of the re-entry programmes were clearly multiple. The results generally affirm the effectiveness and utility of community re-entry programmes. PMID- 1873602 TI - Learning in post-traumatic amnesia following extremely severe closed head injury. AB - Verbal and spatial tests of learning were administered in five repeated sessions to nine subjects who were in post-traumatic amnesia (PTA) following extremely severe closed head injuries. PTA was operationally defined as having a score of 75 or less on the Galveston Orientation and Amnesia Test. Subjects showed no ability to learn verbal information (free recall and recognition of a word list) but showed some savings of spatial location information over the first three sessions. Results were interpreted as suggestive of a primarily passive mode of learning during PTA, regardless of the nature of the material to be learned. PMID- 1873603 TI - Substance abuse and crime patterns among persons with traumatic brain injury referred for supported employment. AB - The present investigation examined the incidence of alcohol use, drug use and criminal behaviour among persons with traumatic brain injury referred for supported employment services. Primary caretakers of 74 consecutive referrals completed the General Health and History Questionnaire, the brief version of the Michigan Alcohol Screening Test, and the Quantity-Frequency-Variability Index. Pre-injury, a fifth of the sample were abstinent from alcohol and 66% were labelled as moderate or heavy drinkers. Post-injury alcohol use declined. Half of the sample were abstinent and 28% were moderate or heavy drinkers. Thirty-six percent reported illicit drug use pre-injury. Reportedly, post-injury drug use declined to an incidence of 4%. Nearly 20% of the sample had been arrested pre injury and 10% were arrested post-injury. Implications for further research and programme development are discussed. PMID- 1873604 TI - Predicting severity of cognitive impairment after severe head injury. AB - It is often assumed that age is an important variable in determining cognitive outcome following severe head injury. The present study was carried out to determine whether age at time of injury predicted severity of cognitive impairment. Our hypothesis was that the older the patient at time of head injury the worse should be the cognitive impairment. Cognitive impairment was assessed by scores on nine standardized tests. Scores were obtained from 144 consecutive referrals to a clinical psychologist; all subjects had sustained a severe head injury. Of these, 115 had suffered a closed head injury. Ages ranged from 13 to 65 years. Apart from Unusual Views and Verbal Fluency no significant correlations were found between age and test performance. Thus there was little evidence that age predicted performance on cognitive tests. A number of significant correlations were found between length of coma and cognitive performance. The findings would seem to confirm that cognitive outcome after severe head injury is predicted by length of coma (which reflects severity of brain damage) whilst age at time of injury does not appear to be a good predictor of outcome. PMID- 1873605 TI - Comparison of minor and severe head injury emotional sequelae using the MMPI. AB - The Minnesota Multiphasic Personality Inventory (MMPI) was administered to 73 patients with traumatic brain injury to objectively evaluate emotional status. Profile analysis indicated that many patients were suffering from emotional disturbance. Higher distress levels were evident among those with minor head injury relative to severe head injury. Observed MMPI profiles for these two head injury groups were consistent with previous research and expectations related to the typical consequences of the post-concussion syndrome. The potential value of the MMPI with the head injury population as well as the need for cautious interpretation and integration of impressions derived from other sources is discussed. PMID- 1873606 TI - The relationship between social skill and family problem-solving following very severe closed head injury. AB - This study examined the relationship between level of social skill and family problem-solving behaviour in a group of 18, community dwelling, very severe closed head injury (CHI) patients who had suffered their injury at least 18 months previously, and who were still in contact with rehabilitation services. The main findings of this study were a positive relationship between CHI patients' level of social skill and their rate of positive effect, and an inverse relationship between the CHI patients' level of social skill and the rate of facilitative behaviour displayed by relatives during problem-solving interactions. It is suggested that socially unskilled CHI patients may be more demanding to interact with, and that this may cause a significant burden for their relatives. PMID- 1873607 TI - Treatment of post-traumatic midbrain resting-kinetic tremor with combined levodopa/carbidopa and carbamazepine. AB - A patient with a post-traumatic midbrain haemorrhagic lesion documented by magnetic resonance imaging (MRI) presented with a combined resting-kinetic contralateral upper extremity tremor. The resting tremor component responded to levodopa/carbidopa, while the kinetic component improved with the addition of carbamazepine. PMID- 1873608 TI - Survival assessment of cultured epidermal allografts applied onto partial thickness burn wounds. AB - Cultured epidermal allografts (C.E.A.) were applied to 6 partial thickness burns. Biopsies were obtained at intervals between 8-100 days after grafting. In the second week clinical re-epithelialisation of the allografted sites was confirmed histologically. Blood group- and sex-mismatch studies showed that the allografted cells were not present between 8-100 days post-grafting, suggesting that the newly formed epithelium was of host origin. PMID- 1873609 TI - Supraperiosteal lifting of the upper two-thirds of the face. AB - This paper presents an alternative to subperiosteal lifting (mask-lift), consisting in making the dissection following the natural plane of the sub-SMAS in the upper and middle thirds of the face. It constitutes what we have called supraperiosteal lifting of the upper two-thirds of the face, or suspension of the fronto-temporo-periorbito-malar SMAS. In our experience, this technique offers certain advantages and has fewer complications than subperiosteal lifting, allowing natural and harmonious rejuvenation of the upper two-thirds of the face, leaving no sequelae other than the coronal scar which is concealed in the scalp. The article describes the surgical procedure and the results obtained, as well as its frequent association with other procedures such as blepharoplasty, modification of the orbital bone rim, malar augmentation, rhinoplasty, cervicofacial lifting etc. PMID- 1873610 TI - A comparative investigation of re-epithelialisation of split skin graft donor areas after application of hydrocolloid and alginate dressings. AB - The performances of hydrocolloid and alginate dressing materials have been compared in a study of 65 split skin graft donor areas. The donor areas were randomised between the two dressing materials. The rates of epithelialisation, the discomfort experienced by the patients and the convenience of the dressings in clinical use were compared. At the time of the first dressing change 87% of the donor areas dressed with the hydrocolloid and 86% of the donor areas dressed with the alginate were found to be more than 90% healed. The mean time from operation to the observation of complete healing was 10.0 days for the donor areas dressed with the hydrocolloid and 15.5 days for the donor areas dressed with the alginate: this difference was found to be statistically significant. The discomfort experienced by the two groups of patients was comparable. The rapid healing associated with the hydrocolloid dressing was thought to be of greatest benefit to inpatients; alginate dressings were thought to be more suitable for outpatients, as they proved to be simpler to use. PMID- 1873611 TI - A randomised controlled study to evaluate the effect of Naftidrofuryl in a rat ischaemic skin flap model. AB - The theoretical benefit of Naftidrofuryl in improving survival of ischaemic skin flaps was tested in a randomised controlled study using oral, intraperitoneal and local administration of the drug in three groups of Wistar rats. The vasodilator Naftidrofuryl was shown to be of no value in preventing distal necrosis in a rat skin flap model which has previously responded to pharmacological manipulation. PMID- 1873612 TI - Modulatory effects of topically administered lidocaine and pentobarbital on traumatic vasospasm in the rabbit ear artery. AB - The effect of topical administration of 2 or 20% lidocaine and of 3% pentobarbital on traumatic vasospasm was studied in the central ear artery of the rabbit. The inner diameter of the artery was measured by in vivo microscopy. Vasospasm was induced by a standardised pinch of a 3.2 mm long arterial segment and lasted for 10-20 min. The drugs were given locally at maximal spasm, 1 min after spasm induction. All treatments caused prompt resolution of the vasospasm. This was followed by a plateau phase when the vessel diameter was reduced to about 60% of the initial pre-spasm value as a result of drug-induced vasoconstriction. The vasoconstriction lasted between 40 min and 24 h, depending on the treatment. Twenty per cent lidocaine was most effective, but caused thrombosis in microvessels surrounding the central ear artery. It is concluded that topical lidocaine and pentobarbital are both effective in resolving traumatic vasospasm but should only be used after careful consideration, since they also cause a general decrease in vascular diameter. PMID- 1873613 TI - "Side table assembly"--an adjuvant to craniofacial reconstruction. AB - Plates and screws are used extensively in craniofacial surgery; they have increased the speed of this surgery, but this can be made even more efficient. Utilising an adjacent instrument table, the rearrangement and reassembly of bone segments resulting from osteotomy or fracture can be performed by a second surgical team using plates and screws. At the conclusion of the operation, the reassembled bony reconstruction can rapidly be placed in position with a minimum of additional screws. This technique has been found to be technically easier and to afford a considerable saving of operating time. PMID- 1873614 TI - Innervation and functional reconstruction of the forehead. AB - The anatomy of the motor and sensory innervation of the forehead was studied by dissection of 10 cadavers. Some of the temporal branches of the facial nerve supply the frontalis muscle. They run along a line drawn from below the tragus to a point about 1.5 cm above the outer margin of the orbit where the branches enter the muscle from its deep aspect. There is wide variation in the number of branches and the pattern of anastomosis between them. The sensory innervation is from the frontal nerve, a branch of the ophthalmic division of the fifth cranial nerve. Although the pattern of division into four or five branches is very variable and often asymmetrical, there is an important common feature: the most medial branch changes from a submuscular to a subcutaneous plane immediately after leaving the orbit, while each of the successively more lateral branches travels to a higher level before this change takes place. On the basis of these anatomical findings, a functionally satisfactory reconstructive procedure was designed to close skin defects of the forehead of up to 6 cm in diameter, by raising innervated musculocutaneous local flaps. PMID- 1873615 TI - New surgical technique for reconstruction of the ala of the nose. AB - A technique is described for reconstructing through-and-through defects of the ala of the nose, using a compound flap from the nasal tip and the opposite ala. It is illustrated with two cases. PMID- 1873616 TI - Lower eyelid repair utilising triangular skin flaps with subcutaneous pedicles. AB - Fifty-four patients were studied during the period from 1984 to 1989. The lower eyelid was repaired in 55 cases utilising a triangular flap with a subcutaneous pedicle. Repair was achieved in 39 cases with a triangular flap only and in 16 it was necessary to use a chondromucosal graft of nasal septum as well. The method is described and is feasible for repairs ranging from the simplest to the most complex in different locations of the lid. PMID- 1873617 TI - The sliding venous flap for covering skin defects with poor blood supply on the lateral aspects of fingers. AB - For the treatment of skin defects with poor blood supply on the lateral aspects of the fingers, particularly the radial side of the index finger and the ulnar side of the little finger which have been difficult to cover conventionally, we have developed the sliding venous flap. The flap can be moved by using the "sag" obtained from the dissected dorsal veins of the same finger. We have applied this technique in six cases with excellent results. The indications are limited to cases with only slight crushing of the dorsum of the finger. We consider this technique safe and effective in covering skin defects with poor blood supply on the lateral aspects of fingers. PMID- 1873618 TI - The inverted nipple: to cut the ducts or not? AB - Much dilemma exists as whether to divide the lactiferous ducts or not when correcting an inverted nipple. We report a series of 26 cases (44 nipples), which have undergone correction with or without duct division. Eversion was maintained in 59% of nipples. Analysis of the failure groups revealed similar rates of failure for umbilicated nipples whether the ducts were divided (27%) or not (25%). Invaginated nipples showed an increased tendency to reinvert postoperatively if the ducts were not divided (80%) than if they were (42%) (not significant). Permanent loss of nipple sensation was noted in 20% of cases when the lactiferous ducts were divided. Postoperatively two women were able to breast feed despite complete division of their lactiferous ducts. Women with umbilicated nipples are usually able to breast feed. We believe that correction of the umbilicated nipple can usually be successfully performed, and function maintained without dividing the ducts. Correction of the invaginated nipple requires duct division. The underlying pathogenesis and varying methods of correction are reviewed. PMID- 1873619 TI - Unoperated bilateral cleft lip and palate in a young adult: a thirty three year follow-up. AB - A 15-year-old patient with an unoperated complete bilateral cleft of the lip and palate was operated in 1955. The premaxilla was sacrificed and replaced with a prosthesis. The prolabium was hypoplastic and was used to reconstruct the columella. A follow-up of 33 years is presented. PMID- 1873620 TI - Nasal augmentation in chondrodysplasia punctata using tissue expansion. AB - Chondrodysplasia punctata is an uncommon group of congenital bone dysplasias. A common feature of this disease is a characteristic facial appearance including nasal hypoplasia. This paper describes the management of a case presenting with this disease in which soft tissue augmentation was achieved with tissue expansion of the nasal skin. Follow-up of more than 4 years demonstrates that a satisfactory result has been achieved, with no facial scars. The relevant literature is discussed. PMID- 1873621 TI - A long surviving case of holoprosencephaly agnathia series. AB - The rare syndrome of the agnathia with microstomia, aglossia, synotia (the external ears approaching one another in the midline) and brain malformation (agnathia-holoprosencephaly) was reported by Pauli et al. (1983) as a developmental field defect. This syndrome has two subgroups. One is more severe with brain malformation (holoprosencephaly), and the other is less severe without brain malformation. This report presents a long surviving case of this syndrome without brain malformation. PMID- 1873622 TI - An anomaly of the radial artery--relevance for the forearm flap. AB - The radial artery runs between the Flexor Carpi Radialis tendon and the Brachioradialis tendon in the distal one-third of the forearm. Here it is covered only by the superficial fascia, subcutaneous tissue and skin, so that it is easy to palpate. However, the case reported here describes a rare anomaly of the radial artery which has relevance to use of the forearm flap. PMID- 1873623 TI - Latissimus dorsi breast reconstruction. PMID- 1873624 TI - The migrating tendon spacer. PMID- 1873625 TI - The marketing of 5-hydroxytryptamine: depression or anxiety? PMID- 1873626 TI - Child psychiatry in developing countries. AB - Child psychiatry in developing countries has recently attained the status of an established specialty. This review looks at available epidemiological data, and factors contributing to similarities and differences in rates of disorder. The relevance of child psychiatry to child health in these countries has service, training and research implications. PMID- 1873627 TI - Dangerous mistakes. AB - The shortening of the periods of detention for treatment, deterrence or retribution have made a live issue of whether (or when) it is justifiable to detain violent and sexual offenders solely for the protection of others. Anti protectionist arguments have made 'dangerousness' a dirty word, but are based either on actuarial statistics of doubtful relevance or on confused moral reasoning. A typology of 'dangerousness' is tentatively offered, and the impossibility of adequately supervising some dangerous offenders in the community is emphasised. That said, offenders detained solely for the sake of others are entitled to more than merely 'humane containment'. PMID- 1873628 TI - Unexplained fluctuations in the risk for schizophrenia by month and year of birth. AB - Variation in their year and month of birth was studied in the 13,661 schizophrenics born between 1914 and 1960 known to the Scottish Psychiatric Case Register. Year-to-year fluctuations in the number of schizophrenics per 10,000 live births were outside chance limits. So were month-to-month fluctuations between January 1932 and December 1960, and this was largely due to fluctuations in the numbers of schizophrenics born in February, March, April and May. Time lagged correlations with mean monthly temperatures suggest that in these same four months the incidence of schizophrenia is influenced by temperature six months previously - the lower the temperature in the autumn the higher the incidence of schizophrenic births the following spring. If these findings can be confirmed in other data sets, they would suggest that some influence which varies consistently with season and temperature is contributing to the aetiology of schizophrenia and may exert its effects as early as the third or fourth month of foetal development. PMID- 1873629 TI - Season of birth in schizophrenia. Evidence for confinement of an excess of winter births to patients without a family history of mental disorder. AB - Although it is well recognised that schizophrenic patients are more often born in winter, the significance of this finding remains obscure. Data relating to season of birth and family history were analysed for 561 patients with an ICD-9 diagnosis of schizophrenia. Patients with no family history of any psychiatric disorder group were significantly more likely to be born in winter than patients with a first-degree relative affected by schizophrenia. In comparison with normal population controls, only those without a family history exhibited a significant excess of winter births, suggesting an environmental factor of greater aetiological significance in these patients. PMID- 1873630 TI - Sex differences in suicidal behaviour of referred adolescents. AB - Reports of suicidal behaviour from four countries using the same measures were higher for girls than for boys, and higher in self-reports than in parent reports for both referred and normal adolescents. In a sample of 480 referred adolescents, patterns of 'low' and 'high' suicidal scores were different when age, sex and diagnosis were considered. The probability of high scores for girls showed only a marginal increase with age, while there was a striking rise for boys. An affective diagnosis doubled the probability of high scores for both boys and girls, while it had no effect on low scores. Psychosocial stressors also increased the probability of high suicidal scores, particularly in adolescents with an affective disorder. Sex differences in suicidal behaviour were marked in the low-scoring groups. PMID- 1873631 TI - Using the Hospital Anxiety and Depression Scale to screen for psychiatric disorders in people presenting with deliberate self-harm. AB - In-patients referred to a deliberate self-harm team were asked to complete the HAD questionnaire and diagnoses were made using the SCID. The total prevalence of psychiatric disorder by DSM-III criteria was 54%. The HAD performed well as a screening instrument; a threshold score of eight gave a sensitivity of 88% and a positive predictive value of 80%; its use by non-psychiatrists to detect depressive disorder in patients presenting with deliberate self-harm is to be recommended. PMID- 1873632 TI - Treatment as an alternative to prosecution: offenders diverted for treatment. AB - In Scotland, procurators fiscal (state prosecutors) can divert certain offenders from the court process into treatment. This paper describes the first diversion scheme in which offenders who are suspected of having psychological difficulties are referred for psychological and psychiatric treatment before, and generally in lieu of, prosecution. It is argued that the procurator fiscal is successful in selecting suitable cases for treatment: most people referred have significant psychological difficulties but have failed to obtain appropriate assistance through the normal channels of referral. PMID- 1873633 TI - Compulsory psychiatric treatment in the community. II. A controlled study of patients whom psychiatrists would recommend for compulsory treatment in the community. AB - Several English consultant psychiatrists were asked to identify which patients currently under their care they would recommend for treatment with a community treatment order, if such a provision existed. The psychiatrists were asked to match each such 'nominated' patient for age, sex and diagnosis with one or two control patients, not considered to require compulsory treatment in the community. From specific data collected, it was found that: the two groups did not differ in their 'lifetime' histories of psychiatric admissions, substance misuse, criminal charges or dangerousness; 65-72% of the total sample had a history of serious dangerousness; but in the 12 months before nomination, the 'nominated' patients were significantly less likely than the controls to have complied with psychiatric treatment, and more likely to have defaulted from follow-up. The results indicate that a psychiatrist's decision to recommend a patient for treatment with a community treatment order will depend predominantly on specific criteria related to the patient's recent past. PMID- 1873634 TI - Adoption and eating disorders: a high-risk group? AB - Between 1975 and 1985, 3.8% of patients referred to the Maudsley Hospital with anorexia and bulimia were adoptees. This exceeds the rate of adoption (1.5%) in the general population matched for year of birth. The 18 adoptees with eating disorders had significantly more associated behavioural disturbance and lower academic achievement than the 18 matched controls, and different precipitating factors. PMID- 1873635 TI - Is schizophrenia disappearing? PMID- 1873636 TI - Pattern of obsessive-compulsive disorder in eastern Saudi Arabia. AB - In 32 Muslim Saudis with obsessive-compulsive disorder, compulsive acts (78%) and doubts (66%) were the commonest forms. Religious themes predominated in both the obsessions and compulsions. PMID- 1873637 TI - Polycythaemia rubra vera, cerebral ischaemia and depression. AB - A patient with polycythaemia rubra vera complicated by severe psychotic depression is described. There have been no previous reports of polycythaemia rubra vera associated with psychiatric morbidity. PMID- 1873638 TI - Successful treatment of paraphilic coercive disorder (a rapist) with fluoxetine hydrochloride. AB - A rape assailant with intrusive and persistent paraphilic rape fantasies was successfully treated with the antidepressant fluoxetine hydrochloride. Symptoms of impulsiveness, anxiety and depression were also markedly improved. PMID- 1873639 TI - Dependence on monoamine oxidase inhibitors in high dose. AB - A 37-year-old woman with a personality disorder and chronic dysthymia developed a dependence on MAOIs. She ingested 440 mg tranylcypromine daily without any side effects while taking no dietary precautions. The features of MAOI dependence and their resemblance to amphetamine dependence are discussed. PMID- 1873640 TI - Dementia with parietal signs. PMID- 1873641 TI - Eating disorders in Asians. PMID- 1873642 TI - Computerised tomography in schizophrenia. PMID- 1873643 TI - Tardive dyskinesia and HLA. PMID- 1873644 TI - Menopausal depression. PMID- 1873645 TI - EPDS by post. PMID- 1873646 TI - Educational status and neurological abnormalities in schizophrenia. PMID- 1873647 TI - Brain lesions and cognitive function in late-life psychosis. PMID- 1873648 TI - Are lateral eye-movements a valid index of functional hemispheric asymmetries? AB - Lateral eye-movements (LEMs) to verbal and spatial questions are frequently used as an index of asymmetries in hemisphere activation and the concept of 'hemisphericity'. There have, however, been few attempts to validate LEMs using independent cognitive measures of hemisphere function. This study relates laterality indices of LEMs recorded in the dark using infrared recording techniques, and elicited by verbal and spatial questions, to other measures of left and right hemisphere functioning (verbal and non-verbal dichotic listening, block design, digit span) in 43 subjects. LEM laterality indices were unrelated to these validation measures. It is concluded that although appropriate question type-LEM relationships may reflect transient asymmetries in hemispheric activation, they are not a valid index of stable individual differences in hemisphere utilization. PMID- 1873649 TI - Do older people know how good they are? AB - Information and procedures that have been overlearned during a lifetime form a body of 'crystallized' intelligence that is relatively unaffected by ageing. Thus in spite of marked decrements in their 'fluid' memory abilities it is possible that older people may retain knowledge about the limitations and characteristics of their own memory ('metamemory'). To test whether efficiency of metamemory is, indeed, independent of age-related decline in fluid intelligence, 320 people aged from 50 to 79 years were asked to predict their probable performance on four simple memory tasks which had been carefully explained to them. They then experienced the tasks and their predictions were compared with their actual performances. Actual task performance was modestly predicted by chronological age and by AH 4 and Mill Hill IQ test scores but not by subjective self-ratings of everyday memory and cognitive efficiency (the Broadbent CFQ, and the Sunderland & Harris MQ). The data suggest that absolute levels of prediction of performance were associated with self-confidence and were best predicted by scores on the Beck depression scale and by fluid IQ test scores. There was also evidence that individuals with higher test scores gave more accurate as well as more optimistic predictions of their own abilities. Taken together these results suggest that the accuracy of individuals' assessments of their own abilities does alter with age related changes in fluid IQ, but probably more radically by age-related changes in self-regard and in life-style. PMID- 1873650 TI - A catastrophe model of anxiety and performance. AB - An experiment is reported which tests Fazey & Hardy's (1988) catastrophe model of anxiety and performance. Eight experienced basketball players were required to perform a set shooting task, under conditions of high and low cognitive anxiety. On each of these occasions, physiological arousal was manipulated by means of physical work in such a way that subjects were tested with physiological arousal increasing and decreasing. Curve-fitting procedures followed by non-parametric tests of significance confirmed (p less than .002) Fazey & Hardy's hysteresis hypothesis: namely, that the polynomial curves for the increasing vs. decreasing arousal conditions would be horizontally displaced relative to each other in the high cognitive anxiety condition, but superimposed on top of one another in the low cognitive anxiety condition. Other non-parametric procedures showed that subjects' maximum performances were higher, their minimum performances lower, and their critical decrements in performance greater in the high cognitive anxiety condition than in the low cognitive anxiety condition. These results were taken as strong support for Fazey & Hardy's catastrophe model of anxiety and performance. The implications of the model for current theorizing on the anxiety performance relationship are also discussed. PMID- 1873651 TI - Humanistic understanding and physiological explanation in the Principles. PMID- 1873652 TI - James and Freud: two masters of metaphor. PMID- 1873653 TI - William James's The Principles of Psychology: 'a seemingly inexhaustible source of ideas'. AB - Selected topics from The Principles of Psychology are evaluated in the light of current psychological knowledge. It is argued that James's main contribution lies in his acute observation of experience, resulting in the framing of searching questions about fundamental problems, and that many of his insights have inspired recent work. This is illustrated with reference to his chapters on the will, attention and emotion. The main advances since his time have been in the reformulation of his ideas in information-processing terms, enabling their empirical testing in laboratory experiments, computer simulation and neuropsychology. PMID- 1873654 TI - The Guidance Notes revisited: advice to patients leaving hospital after diagnostic nuclear medicine. PMID- 1873655 TI - Lymphoproliferative disorders of the thyroid gland: radiological appearances. AB - Images of lymphoproliferative disorders of the thyroid by ultrasonography (US), computed tomography (CT), 99Tcm and 67Ga scintigraphy were analysed in eight patients (two men and six women, aged 42-83 years). Seven patients were diagnosed as having primary lymphoma and one plasmacytoma. Ultrasound revealed a solid mass with homogeneous and very low echogenicity clearly distinguishable from residual thyroid tissue in five patients, diffuse hypoechoic goitre in one and multiple irregular hypoechoic nodules in both lobes in the patient with plasmacytoma (Case 8). Computed tomography demonstrated a focal low-density area in six cases of lymphoma and decreased density throughout the gland in the other two patients. 99Tcm scintigraphy showed hemilobar enlargement with decreased and uneven trapping, cold area or complete lobar defect in six patients with lymphoma and no trapping in the case of plasmacytoma. 67Ga scintigraphy demonstrated high accumulation in lymphoma and faint accumulation in the case of plasmacytoma. Radiological manifestations with a focal lesion were considered typical and diagnostic of primary thyroid lymphoma, while in one case with diffuse infiltration through the whole gland, the differential diagnosis from Hashimoto's thyroiditis could not be made. In the final case, cells infiltrated diffusely to form islands with patchy distribution among well preserved follicles, correlating with the multiple hypoechoic areas observed by US. PMID- 1873656 TI - Fibrous dysplasia of the skull: disease activity in relation to age. AB - Eighteen of 19 patients with histologically confirmed fibrous dysplasia of the skull seen at the Institute of Neurological Sciences, Glasgow, in the past 20 years have been reviewed and recent radiographs obtained. Sex, age at presentation and at follow-up were recorded, in addition to the site, type and extent of cranial involvement. The findings have been related to disease activity and progression. In comparison with other reports we found the proportion of patients with activity in adulthood to be relatively high (37%). Overall, there was an equal sex distribution, but of seven patients presenting as adults, six were female as were six of seven patients with evidence of disease activity in adulthood. PMID- 1873657 TI - The extrapleural fat in empyema: CT appearance. AB - Pleural empyema can be accompanied by changes in the adjacent chest wall. We examined the chest wall on computed tomographic scans in 24 patients with pleural effusions. Eighteen patients had pleural empyema and six had transudative effusions. Of the 18 empyema patients, 13 had abnormally high attenuation in the extrapleural tissues. In 12 of these 13, the high attenuation was probably caused by reaction to the pleural infection. In two, it was probably caused by haematoma (one patient had haematoma and empyema). In five patients there was either no clear abnormality in the extrapleural space or an insufficient amount of fat to permit detection of an abnormality, or the parietal pleura could not be distinguished from the pleural fluid because intravenous contrast medium was not given. Of the six patients with proven transudative pleural effusions, all had extrapleural fat which appeared normal. Abnormally high attenuation in the extrapleural tissues can be expected to accompany exudative pleural effusion, particularly empyema, but not transudative effusion. PMID- 1873658 TI - The ocular effects of hyoscine-n-butylbromide ("Buscopan") in radiological practice. AB - "Buscopan" (hyoscine-n-butylbromide, HBB) is a smooth muscle relaxant regularly used in radiological and endoscopic procedures. One unwanted effect is temporary impairment of visual accommodation. Near and distance vision were assessed in 100 patients undergoing barium meal and barium enema studies. Visual testing was performed prior to the examination and repeated immediately before leaving the radiology department. Completed data was obtained in 90 patients. Of these, 37 were given a conventional 20 mg intravenous dose of HBB, 37 were given glucagon and 16 received no drug. No patient showed any impairment of distance vision. Minor abnormalities of near vision were observed in five patients. All had been given HBB. They were aged 50 years or less and had been retested 12-21 min after administration of the drug. It is suggested that the degree of visual impairment observed is not sufficient to impair driving ability. Routine questioning concerning history of glaucoma is unlikely to be of value; more appropriate would be a warning to seek urgent medical advice if eye pain or visual loss is experienced. PMID- 1873659 TI - A comparison between iotrolan, a non-ionic dimer, and a hyperosmolar contrast medium, Urografin, in hysterosalpingography. AB - For hysterosalpingography, there were no significant differences between the non ionic dimeric contrast medium iotrolan (300 mgI/%) and Urografin (370 mgI/%) with regard to ease of application or radiographic quality, and both agents were equally suitable. There were no significant differences between two groups of patients with regard to pain due to instrumentation, pain at the time of injection and pain up to 2 h after the procedure. There was a significant difference (p = 0.04) between the two groups with respect to delayed pain, when iotrolan was associated with a lower incidence and decreased severity of delayed pain. There were no differences in the incidence of nausea, vomiting, headache and syncope. No allergic phenomena were seen in either group. PMID- 1873660 TI - Real-time digital contrast enhancement and magnification in the assessment of acute elbow injuries. AB - The elbow is a common site of injury and missed fractures may lead to disability and litigation. An assessment was made of a commercially available desk-top digital contrast enhancement and magnification unit (DETECT system) in a series of 320 patients with an acute elbow injury. Five radiologists of varying experience independently viewed elbow radiographs on a conventional light-box, and subsequently using the digitizer, indicating the presence or absence of a fracture. The overall results demonstrated no difference in performance when using the unit, though small improvements in the confidence with which a definite diagnosis was made were observed. Assessment of soft tissues with the digitizer was less reliable. PMID- 1873661 TI - Clinical application of an electronic imaging device for assisting patient set-up in radiotherapy. AB - As radiotherapy treatment set-ups are becoming more complicated and a greater emphasis is placed on accuracy, there is an increasing need to verify and record the actual treatments being given. A direct electronic imaging device is currently marketed by Varian (the DYNARAY ID), which uses the latest technology in detection and image processing to obtain digital images of the patient's anatomy using the actual treatment beam. At Norwich we have been using a prototype machine in a busy district radiotherapy centre and have examined over 50 patients. We have found the images easy to obtain and the technique superior to the standard practice of using verification radiographs. The role of this device lies in aiding quality assurance of treatments whilst generating a permanent record of the actual treatment given. PMID- 1873662 TI - Anaphylactoid reaction associated with the use of 99Tcm hexamethyl propylene amine oxime as a leukocyte labelling agent. PMID- 1873663 TI - Radiology of secondary amyloidosis of the stomach in a patient with rheumatoid arthritis. PMID- 1873664 TI - Sling left pulmonary artery with congenital airway stenosis: non-invasive investigation and conservative management? PMID- 1873665 TI - Laurence-Moon-Biedl syndrome: renal ultrasound appearances in the neonate. PMID- 1873666 TI - Intracranial chondrosarcoma in a patient with Ollier's disease. PMID- 1873667 TI - A clinical red herring. PMID- 1873668 TI - A new phantom for mammography. PMID- 1873669 TI - Scoring of image quality phantom films in mammography. PMID- 1873670 TI - Body aprons in radiation protection. PMID- 1873671 TI - The role of the single photon emission computed tomography (SPECT) in detection of ossific mediastinal and pulmonary metastases. PMID- 1873672 TI - Proceedings of the British Medical Ultrasound Society. 22nd annual meeting. Harrogate, December 4-6, 1990. Abstracts. PMID- 1873673 TI - Photodynamic therapy. PMID- 1873674 TI - A user's guide to flexible cystoscopes. AB - This survey, carried out on behalf of the BAUS Instruments Committee, aims to assist the urologist in choosing a flexible cystoscope. The 5 most commonly available flexible cystoscopes (from ACMI, Olympus, Pentax, Storz and Wolf) were assessed in a clinical setting for handling, image quality and user satisfaction. Several technical characteristics, including deflection range, irrigant flow rate and optics, were tested in the laboratory. Whilst all instruments were satisfactory, the favourite of our testing panel was the Olympus CYF-2, which also came out best in the technical assessment and has the most comprehensive service support. The cheaper Storz instrument also performed well. PMID- 1873675 TI - Retrovesical hydatid causing haemospermia. PMID- 1873676 TI - Rupture of false aneurysm secondary to passage of ureteric stent. PMID- 1873677 TI - Verrucous carcinoma of the penis successfully treated with interferon. PMID- 1873678 TI - Nephrogenic adenoma of the ureter. PMID- 1873679 TI - Possible relationship of bladder exstrophy and epispadias with progestins taken during early pregnancy. PMID- 1873680 TI - Ureteric tumour in a duplex system. PMID- 1873681 TI - Bladder exstrophy complicated by adenocarcinoma. PMID- 1873682 TI - Use of a straw for suprapubic stab puncture--an alternative method. PMID- 1873683 TI - Transbrachial approach in spermatic phlebography. PMID- 1873684 TI - Extracorporeal shockwave lithotripsy or extracorporeal piezoelectric lithotripsy? Comparison of costs and results. AB - One thousand patients with renal stones up to 3 cm in diameter were divided equally into 2 groups matched for age, sex and stone size. One group was treated on the Dornier HM3 lithotriptor and the other on the EDAP LT01. The results showed that for stones less than 1 cm both lithotriptors were equally effective, with a stone-free rate of 87.5% for the Dornier and 90.4% for the EDAP at 3 months. The success rate fell more steeply for the EDAP machine, however, to become 77.2 and 42.5% respectively as the stone size increased to 3 cm. Treatment time was longer on the EDAP lithotriptor and more sessions were required but patients preferred it to the Dornier. Running costs per patient were higher on the EDAP. PMID- 1873685 TI - Anaesthesia-free extracorporeal shock wave lithotripsy in patients with renal calculi. AB - Modern extracorporeal shock wave lithotripsy can be performed with combined ECG and respiratory triggered shock wave release. Disconnecting the ECG triggering increases the risk of ventricular arrhythmias, including potentially malignant ones. The aim of this study was to assess the relationship of any sympatho adrenal excitation as a possible explanation for the occurrence of cardiac arrhythmia. Plasma catecholamine levels were assessed in 5 patients during and after 50 min of anaesthesia-free extracorporeal shock wave lithotripsy for the treatment of calculi in the upper pole of the left kidney. Venous blood sampling showed no significant increase in catecholamines (epinephrine, norepinephrine and dopamine) during or after treatment. The heart rate and arterial blood pressure were measured simultaneously and showed no significant increase when shock waves were released during ECG triggering. However, when disconnecting the ECG triggering mode, the incidence of ventricular extrasystoles on Holter monitoring became more apparent during respiratory triggered shock wave release only, although there was no rise in plasma catecholamine levels. These data suggest that cardiac arrhythmias are related to direct and accidental mechanical stimulation of the heart rather than to any sympatho-adrenal discharge during shock wave release. PMID- 1873686 TI - Do not catheterise your nephrectomies. AB - A retrospective study of 100 consecutive nephrectomy patients showed a 20% catheterisation rate. Of the 11 carried out post-operatively only 4 were for urinary retention. The post-operative catheterisation rate for males was 7.1% and for females 2%. The rate of post-operative retention was 4.4%, which is much lower than that reported from other units. This rate of post-operative catheterisation for retention is so low that in spite of the very mild increase in complications compared with intra-operative catheterisation, the practice of routine prophylactic catheterisation of nephrectomy patients is unnecessary and cannot be recommended. PMID- 1873687 TI - The effect of cromakalim on the normal and hyper-reflexic human detrusor muscle. AB - Cromakalim is a benzopyran derivative which relaxes smooth muscle, probably by opening membrane potassium channels. This study tested the effect of cromakalim on spontaneous, electrically induced and pharmacologically induced contractile activity of normal and hyper-reflexic human detrusor muscle samples. All 3 types of contractile activity were reduced in the presence of cromakalim. A preliminary clinical trial of cromakalim was conducted, the results of which also suggest that this type of drug may have a significant role in the treatment of detrusor instability and hyper-reflexia. PMID- 1873688 TI - Long-term effect of pelvic floor exercises on female urinary incontinence. AB - In order to assess the permanent effect of pelvic floor exercises on female stress incontinence, 76 incontinent women, referred for incontinence surgery, underwent a 3-month exercise programme conducted by an experienced physiotherapist. The patients were followed up for 1 year. At the last assessment 30% were cured and 17% improved. Altogether 47% avoided surgery. No relapses were seen during the follow-up period. Patients with mild incontinence benefited from intensified training, since 72% could expect to be cured, while patients with severe incontinence and no immediate effect did not benefit from further exercises. Patients with a positive hormone status and those with normal weight had a significantly higher cure rate. The subjective results were confirmed by the 24-h pad test. Anal pressure profilometry was a valid method for instruction and objective control of pelvic floor function. It was concluded that pelvic floor exercises should precede surgery, since exercises had a permanent effect in half of the patients. PMID- 1873689 TI - Clam enterocystoplasty in general urological practice. AB - A series of 45 patients (31 female) underwent clam enterocystoplasty for urgency and incontinence. The majority had detrusor instability. Prolonged conservative treatment had failed in all cases. Improvement occurred in 71% and those younger than 30 years had better overall results; 29% remained incontinent, with 9% requiring a urinary diversion. Many patients did not achieve maximum benefit until 9 months post-operatively. Surgery had no statistically significant effect on any urodynamic parameter and post-operative complications were common. The operation was performed in either the coronal (19) or the sagittal plane (26); this did not influence results. In general, surgery was found to be technically simpler in the sagittal group and it is recommended that this becomes the standard procedure. We feel that this operation involves major surgery and should only be offered with reluctance. PMID- 1873690 TI - The significance of an open bladder neck in women. AB - The significance of an open bladder neck at rest has been investigated in 147 women presenting to a urodynamic clinic. The prevalence of this condition was 21%; there was an association with urethral sphincter incompetence but an open bladder neck was not diagnostic of it. It is suggested that the finding of an open bladder neck at rest during urodynamic investigation is of little consequence. PMID- 1873691 TI - Measurement of in vivo urological tumour cell kinetics using multiparameter flow cytometry. Preliminary study. AB - The in vivo labelling of urological tumour cells using the S phase marker bromodeoxyuridine (BRdU) for histochemical studies is reported. The use of multiparameter flow cytometry (FCM) with BRdU labelling to study tumour proliferation offers significant advantages. It provides simultaneous measurements of the DNA ploidy (DI), the duration of the S phase (Ts), the potential doubling time (Tpot) and the total and aneuploid tumour labelling indices (LI) from a single specimen. Heterogenous tumour cell populations can be measured with high sensitivity. We report a preliminary study to evaluate the method in the measurement of the kinetics of transitional cell carcinoma of the bladder (TCCB). Nineteen patients with TCCB, 1 with leukoplakia of the bladder, 2 with renal carcinoma, 1 with prostatic carcinoma and 1 with a squamous carcinoma of the penis were studied. Of the bladder tumours, 3 were aneuploid, DI = 1.32, 1.58 and 1.89. BRdU uptake was detected in all tumours. The median LI was 1.5% (range 0.5-10.0). In 15/19 tumours the labelling profile was satisfactory for calculation of the Ts and Tpot. The median Ts was 6.2 h and the median Tpot was 17.1 days. This study demonstrates that measurement of multiple parameters of urological tumour proliferation in vivo is possible. These parameters require further assessment as indices of biological aggressiveness and clinical prognosis. PMID- 1873692 TI - The human prostate gland: a histochemical and immunohistochemical study of neuropeptides, serotonin, dopamine beta-hydroxylase and acetylcholinesterase in autonomic nerves and ganglia. AB - Different regions of the prostate gland, namely the prostatic capsule, peripheral prostate, and proximal and distal central prostate, were obtained from 5 patients with carcinoma of the bladder and studied histochemically and immunohistochemically to localise acetylcholinesterase (AChE)-, dopamine beta hydroxylase (DBH)-, serotonin- and peptide-containing nerves. Autonomic ganglia were found in all regions of the prostate studied. The greatest number of ganglia contained AChE and neuropeptide Y (NPY) followed (in decreasing order) by DBH; [Met]enkephalin (mENK) and [Leu]enkephalin (IENK); calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP); and serotonin, but not somatostatin. The greatest density of nerve fibres was found in the proximal central prostate, followed by the anterior capsule and distal central prostate, with the least in the peripheral prostate. The greatest number of nerve fibres contained ACh and NPY, followed in decreasing order by VIP and DBH; IENK, serotonin and CGRP; mENK; substance P and somatostatin. The functions of the neurotransmitter substances in the human prostate remain to be elucidated. PMID- 1873693 TI - Hospitalisation of prostatic cancer patients undergoing orchiectomy. AB - We report our experience with 100 orchiectomies for advanced prostatic cancer in hospitalised patients. Approximately 60% of the patients required hospitalisation for additional treatment and investigation of complications due to their disease at the time of orchiectomy. In 51 cases the orchiectomy was combined with transurethral resection of the prostate (TURP); 37 patients had pathological levels of serum creatinine and 17 had pathological dilatation of the upper urinary tract, 6 of whom required a nephrostomy catheter. Because of anaemia on admission, 21 patients received a peri-operative blood transfusion. Two patients had significant post-operative bleeding, 2 developed a wound infection and 1 had a deep thrombophlebitis. The patients' mean age was 76.4 years and the period of hospitalisation ranged from 3 to 150 days with peaks at 3 and 8 days. The most important reason for prolonged hospitalisation was social problems. It was concluded that many patients who were hospitalised as a direct consequence of their prostatic carcinoma would have been in hospital for a similar period regardless of the method of hormonal manipulation used. Because so many patients have other reasons for hospitalisation, or require additional surgical procedures such as TURP, the true average cost of orchiectomy for advanced prostatic cancer is difficult to determine. PMID- 1873694 TI - Morphometric evidence for bone resorption and replacement in prostate cancer. AB - A series of 78 patients with metastatic bone disease from prostate cancer underwent iliac crest biopsy, enabling histomorphometric quantification of eroded bone surface and bone volume in both tumour-free and metastatic bone tissue. Eroded surfaces in tumour-free specimens were high in patients with active compared to stable disease but bone volume was maintained in both groups, whilst in bone surrounding micrometastases (n = 8) eroded surfaces were further increased and bone volume reduced. Eroded surfaces within metastases were greater still but were associated with increased bone volume due to replacement of the existing trabecular tissue with abnormal woven bone, giving an overall appearance of sclerosis. These results show that the effect of prostate cancer on bone tissue is complex, involving differential disturbance of bone formation and resorption within metastases, in bone surrounding tumour invasion and in the tumour-free skeleton. PMID- 1873695 TI - Neurophysiology of the striated urethral sphincter in multiple sclerosis. AB - Urethrovesical dysfunction is common in patients with multiple sclerosis. We present the results of urodynamic and neurophysiological studies in a series of 24 patients with multiple sclerosis associated with urinary symptoms. Urethral sphincter electromyography showed only minor abnormalities but studies of central conduction demonstrated abnormal sensory conduction in 88% and abnormal motor conduction in 80% of the patients studied. These abnormalities of central conduction correlated well with the urodynamic findings. PMID- 1873696 TI - Forced hydration prior to renography in children with hydronephrosis. An evaluation. AB - We have developed a method of diuretic renography for the assessment of upper urinary tract obstruction in children. A maximal diuresis under standardised conditions is obtained by forced intravenous hydration over a 2-h period prior to renography. We evaluated the predictive value of this method for the clinical and functional outcome in 73 children with apparent unilateral pelviureteric junction obstruction. The predictive value of a non-obstructive pattern was 94%, while the predictive value of an obstructive pattern could not be assessed accurately because the patients concerned subsequently underwent operation. The method is safe and reliable and offers advantages over conventional diuretic renography. PMID- 1873697 TI - Spontaneous regression of metastatic renal carcinoma with long-term survival. PMID- 1873698 TI - Intra-arterial chemotherapy for breast cancer. PMID- 1873699 TI - Improving survival in gastric cancer: review of operative mortality in English language publications from 1970. AB - In this review of English language publications from 1970, operative mortality following surgery for gastric cancer has been analysed. Operative mortality has declined in series reporting operations in successive decades to 1970, 1980 and 1990. Series reporting patients having surgery for gastric cancer in the decade to 1990 show a mean operative mortality rate of 7.8 per cent (median 4.6 per cent). This improvement may have contributed to the declining mortality rates for gastric cancer in the face of unchanging surgical workload. Results of operations for gastric cancer should be reported in a standard manner. PMID- 1873700 TI - Statistical guidelines for The British Journal of Surgery. AB - A set of statistical guidelines is presented which should be followed by authors preparing manuscripts for submission to The British Journal of Surgery. Simple points relating to presentation are explained in full, and more complex issues are highlighted and discussed in an accompanying review article. PMID- 1873701 TI - Accuracy of endosonography in the staging of rectal cancer treated by radiotherapy. AB - Endosonography is the best available method for the pretherapeutic staging of rectal cancer. The present prospective study was to determine the influence of previous radiotherapy, widely used in the management of this tumour, on the accuracy of endosonography. A complete endosonographic examination was performed just before surgery in 40 patients with rectal cancer. Endosonographic and pathological staging were compared in group A, 21 patients without previous radiotherapy, and group B, 19 patients with preoperative radiotherapy. While the endosonographic accuracy for lymph node involvement was similar in the two groups (85 per cent compared with 84 per cent), wall invasion was correctly ascertained in 86 per cent in group A but in only 47 per cent in group B (P less than 0.05). After irradiation, the thickening of the rectal wall and the poor visualization of the hyperechoic layers hampered interpretation. Post-radiotherapy inflammation and/or fibrosis probably explained the echographic changes. Radiotherapy therefore altered endosonographic staging of rectal cancer. New interpretation criteria are needed for evaluation and follow-up of rectal cancer treated by radiotherapy. PMID- 1873702 TI - Use of the ultrathin choledochoscope in cholecystectomy. AB - Use of the ultrathin choledochoscope (2mm) was evaluated in 80 patients undergoing routine cholecystectomy. It was used successfully in 67 (84 per cent) patients. There were eight (12 per cent) explorations of the common bile duct and no negative explorations. The instrument was helpful in determining the nature of an equivocal on-table cholangiogram. The ultrathin choledochoscope may be useful in reducing the rate of negative common bile duct exploration. PMID- 1873703 TI - Rebound tenderness test. AB - The usefulness of the rebound tenderness test in indicating peritonitis was prospectively assessed in 142 unselected patients admitted as emergencies with abdominal pain and tenderness. It was found to be of no predictive value. PMID- 1873704 TI - One hundred patients with hepatic metastases from colorectal cancer treated by resection: analysis of prognostic determinants. AB - One hundred patients with hepatic metastases from colorectal cancer underwent 'radical' liver resection from 1980 to 1989. At least 1 cm of normal parenchyma surrounded the tumour and no microscopic invasion of resection margins was evident. The disease was staged according to our own staging system. Lobectomy was performed in 50 patients and non-anatomical resection in the remainder. The postoperative mortality rate was 5 per cent and the major morbidity rate was 11 per cent. The actuarial 5-year survival rate for patients in stages I, II and III was 42 per cent, 34 per cent and 15 per cent respectively (P less than 0.001). The overall actuarial 5-year survival rate was 30 per cent. The prognostic importance of various patient and tumour variables was evaluated by univariate analysis and then by multivariate analysis. Age of patient, site of primary, disease-free interval between treatment of primary and of hepatic metastases, preoperative carcinoembryonic antigen levels, and number of metastases, did not relate to prognosis, while sex (P = 0.024), stage of primary (P = 0.026), extent of liver involvement (P less than 0.001), distribution of metastases (P = 0.01) and type of surgery (P = 0.028) significantly affected prognosis as single factors. Multivariate analysis revealed that only the extent of liver involvement and stage of the primary tumour were independent predictors of survival. We conclude that liver resection is effective in selected patients with hepatic metastases from colorectal cancer. In resectable patients it is not yet possible to formulate a clear prognosis based on clinical factors. The extent of liver involvement and the staging system used may be significant, although not absolute, indicators of outcome. PMID- 1873705 TI - Controlled hepatic bipartition for transplantation in children. PMID- 1873706 TI - Surgical anatomy of donor extended right trisegmentectomy before orthotopic liver transplantation in children. AB - Liver transplantation is now accepted as the treatment of choice for children with end stage liver disease. A major constraint has been the shortage of donor organs of appropriate size. The use of reduced size adult organs has partially alleviated this problem but the previous technique employed was limited to a donor:recipient body-weight disparity of not greater than 3:1. Recently a new technique has been described that allows safe transplantation with a donor:recipient weight ratio of greater than 10:1. This should greatly increase the paediatric donor pool. Anatomical landmarks and techniques necessary for donor reduction hepatectomy are described from the dissection of 50 adult cadaveric livers. Variations in all important biliary and vascular structures necessitated adjustments in operative technique. PMID- 1873707 TI - Extracorporeal shock wave treatment of common bile duct stones: experience with two different lithotriptors at a single institution. AB - Extracorporeal shock wave lithotripsy (ESWL) is a new treatment modality for retained common bile duct stones. Sixty-two patients (mean age 75 years, range 27 95 years) with retained common bile duct stones were treated with two different lithotriptors. One of the lithotriptors operated on the electrohydraulic principle (Dornier HM-3) (n = 13), the other on the electromagnetic principle (Siemens Lithostar) (n = 49). All HM-3 patients were treated under general anaesthesia, whereas with the Lithostar one patients was treated under general anaesthesia, 43 received analgesia and sedation and five had no analgesia at all. Patients treated with the Lithostar had more sessions (mean 1.9 versus 1.3, P less than 0.05) and needed more stock waves (mean 8611 versus 2534, P less than 0.001) than patients treated with the HM-3. Fragmentation was achieved in all patients treated with the HM-3 and in 42 (86 per cent) patients treated with the Lithostar. In this latter group ten patients underwent common bile duct exploration without complications. Eleven patients had transient haematuria after treatment with the HM-3 and two patients (one in each group) had a subcapsular haematoma of the right kidney, all without clinical sequelae. At follow-up (median: HM-3 43 months, Lithostar 18 months), none of the patients had biliary complaints. We conclude that ESWL of retained common bile duct stones in safe and effective with both lithotriptors and should be considered before surgery in the elderly or high-risk patient. PMID- 1873708 TI - Successful reuse of a liver graft. PMID- 1873709 TI - Results of surgery for duodenal ulcer: assessment by patients. AB - A questionnaire was administered to 224 patients who had undergone 246 operations for duodenal ulcer to see how well this correlated with Visick grading and to provide insight into the patients' feelings about the results of their surgery. The patients were divided into three groups by Visick grade: good (grade I, n = 70), satisfactory (grades II and IIIs, n = 104) and poor (grades IIIu and IV, n = 72). The distribution of questionnaire responses in each group was statistically different (P less than 0.01). Dividing the questionnaire responses into three corresponding groups, 72 per cent of patients assigned themselves to the same group as their Visick grade. Three observations were made regarding the Visick system: recurrent ulceration is over-scored and should be included only if symptomatic; grading should acknowledge a wider range of symptoms related to ulcer disease and its treatment; only three grades are necessary. PMID- 1873710 TI - Problems in the definition and treatment of early gastric cancer. AB - Radical operation with extensive dissection of lymph nodes (R1, 48 patients; R2, 196 patients; R3, one patient) was performed in 245 out of 247 patients with early gastric cancer. The 5-year survival rate was only 73.2 per cent in the 34 patients with lymph node metastases (31.8 per cent). Analysis of factors influencing recurrence revealed that not only lymph node metastases but also the depth of cancer invasion could affect prognosis in early gastric cancer. This study suggests that radical operation with complete dissection of the first and second group of lymph nodes (R2 resection) is a safe and appropriate treatment even for early gastric cancer. We propose that the definition of early gastric cancer be modified to 'carcinoma with invasion confined to the mucosa or submucosa and without evidence of lymph node metastases'. PMID- 1873711 TI - Surgical treatment of carcinoma of the gastric stump. AB - To evaluate retrospectively the surgical treatment of patients with gastric stump cancer following gastrectomy for benign disease, we reviewed 52 patients operated on at the National Cancer Centre, Tokyo, between 1962 and 1988. Resection was carried out in 47 patients (90 per cent) and with curative intent in 36 (69 per cent). Stage distribution was: stage 1, 15 patients; stage 2, 5; stage 3, 9; stage 4, 23. In 36 cases curatively resected, 32 had completion total gastrectomy and four had subtotal resection. An R1 resection was performed in 11 patients and an R2 in 25. We had two hospital deaths and a 5-year survival rate excluding hospital deaths of 39 per cent. The 5-year survival rates of resected cases, curative cases and those having metastatic nodes were 43 per cent, 57 per cent and 29 per cent respectively. Radical resection is a reasonable treatment for gastric stump cancer as it is for primary cancer of the stomach. PMID- 1873712 TI - Lymph node counts in the upper abdomen: anatomical basis for lymphadenectomy in gastric cancer. AB - The number of regional lymph nodes was determined in sites relevant to lymphadenectomy in gastric cancer in 30 cadavers. Tissue was cleared by dissolving fatty tissue, thus making lymph nodes with a diameter of at least 1 mm visible. All lymph node stations indicated by the Japanese Research Society for Gastric Cancer were studied. In stations 1-11 (corresponding with R2 resection) an average of 27 nodes (range 17-44 nodes) was found, whereas stations 1-16 (corresponding with R3 resection) showed an average of 43 nodes (range 25-64 nodes). These values are higher than those usually obtained from lymphadenectomy for gastric cancer. Striking individual differences in the total number of lymph nodes and the number of single stations was observed. The number of lymph nodes in these investigations are the normal anatomical values and serve as quality control of lymph node dissection in gastric carcinoma. PMID- 1873713 TI - Clinical significance of the large adrenal mass. AB - Current clinical teaching indicates that large (greater than 5 cm in diameter) adrenal masses are often malignant. In a retrospective analysis of patients studied between 1977 and 1988 with computed tomography (CT), adrenal scintigraphy, and when available, magnetic resonance imaging (MRI) 45 were found to have adrenal masses greater than 5 cm (range 5-19 cm) in diameter. Thirty were benign (16 phaeochromocytomas, six adrenocortical adenomas, four adrenal cysts, two myelolipomas, an adrenal hematoma and a ganglioneuroma). Of 15 malignant masses, there were seven adrenocortical carcinomas, five adrenal metastases and three adrenal lymphomas. With the exception of the adrenal myelolipomas, cysts, and the ganglioneuroma neither CT nor MRI demonstrated sufficient diagnostic specificity to distinguish benign from malignant lesions. Functional scintigraphy with 131I-6-beta-iodomethyl-19-norcholesterol for suspected adrenocortical lesions and 131I-metaiodobenzylguanidine for suspected phaeochromocytomas frequently provided useful information. PMID- 1873714 TI - Success and failure with neonatal tracheo-oesophageal anomalies. AB - In seven and a half years, one surgical team treated 67 consecutive neonates with oesophageal atresia and/or tracheo-oesophageal fistula. According to Waterston's classification, 28 were in group A, 12 in group B and 27 in group C. The mortality rate during the initial admission was 10 per cent, all seven deaths being unavoidable in infants in group C with multiple anomalies. Birthweight alone had no bearing upon the chances of survival. Primary oesophageal repair, including one suture-fistula procedure and one delayed primary repair, was attempted in 54 (84 per cent) of the 64 patients with atresia and was successful in 46 (85 per cent). All three H-type tracheo-oesophageal fistulae were successfully divided in infants in group A. Recurrent tracheo-oesophageal fistula developed in four (7 per cent) infants, one of whom (group A) underwent successful repair. One disrupted anastomosis was successfully resutured (group A), so an intact oesophagus was finally achieved in 51 patients, of whom six (12 per cent) developed anastomotic strictures and 21 (41 per cent) underwent surgery for gastro-oesophageal reflux. Of the 60 early survivors, 10 (17 per cent) underwent aortopexy for tracheomalacia. Whenever possible, primary repair is advocated in all infants. Even for those in group C with multiple, severe associated anomalies, the combined early and late mortality was no greater following primary repair (7 died of 12 operated) than after staged repair (4 died of 7 operated), but major anastomotic complications were more common in infants in group C (5 out of 19) than in those in groups A and B (3 out of 38). PMID- 1873715 TI - Necrotizing fasciitis. AB - Ten cases of necrotizing fasciitis are reviewed. Three patients died but only two of these deaths were due to uncontrolled septicaemia. All isolated organisms were sensitive to a combination of piperacillin and ampicillin which we now regard as the initial antibiotic combination of choice. Prompt and aggressive surgical debridement remains the cornerstone of management. PMID- 1873716 TI - Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988. AB - A retrospective analysis was undertaken of all surgical patients in Malmo, Sweden, during the period from 1951 to 1988 in whom pulmonary emboli were found at autopsy. The analysis included a comparison with the earlier analysed and reported time period from 1951 to 1980. A continued high frequency of pulmonary embolism at autopsy was seen during the 1980s (20.3 per cent of deaths, 31.7 per cent of autopsies). Of the 391 autopsy-verified pulmonary emboli found between 1981 and 1988, 113 (28.9 per cent) were considered fatal, 104 (26.6 per cent) contributed to death and 174 (44.5 per cent) were incidental. Few patients had symptomatic deep vein thrombosis or pulmonary embolism before death. The overall frequency of major pulmonary embolism in surgical patients remained unchanged (0.3 per cent). The frequency of major postoperative pulmonary embolism showed an increase during the 1950s and 1960s (maximum 0.4 per cent) but a decrease in the last 5-year period of the 1970s (0.3 per cent), which has earlier been reported upon. This decrease continued during the 1980s (0.2 per cent) (P less than 0.05). An increase was found in the number of patients operated on who had autopsy proven pulmonary embolism and who received thromboprophylaxis. Pulmonary embolism continues to be a major cause of death in surgical patients; however, postoperative major pulmonary embolism has shown a reduction in the last 15-year period. PMID- 1873717 TI - Fibrinolytic activity of the arms and legs of patients with lower limb venous disease. AB - Clearance of subcutaneous 125I-labelled fibrin was prolonged from the legs but not from the arms of patients with uncomplicated varicose veins and patients with healed ulcers, compared with controls. The euglobulin clot lysis time (ECLT) of blood from the arms and legs of those with healed ulcers was prolonged; venous congestion significantly shortened the ECLT of blood from all limbs except legs with healed ulcers. The clearance of interstitial fibrin of both legs and arms correlated with the response of the ECLT to venous congestion (P less than 0.05). The clearance of interstitial 125I-labelled albumin in five patients with healed ulcers was faster from the legs than from the arms, whereas the clearance of interstitial 125I-labelled fibrin was faster from the arms in all cases. These results suggest that there is a defect in interstitial fibrinolytic activity as well as vein wall production of plasminogen activator in legs with chronic venous insufficiency. PMID- 1873718 TI - Time trends in incidence rates of acute, non-traumatic extremity ischaemia: a population-based study during a 19-year period. AB - Time trends in the occurrence of acute limb ischaemia were studied from 1965 to 1983 in a defined geographical area in Sweden. Data were obtained from a computerized register which covers all instances of inpatient care for a population of 1.3 million. Analysis based on 5394 first admissions for acute arterial occlusion revealed that the annual number increased by 2.7 per cent yearly in women and 3.9 per cent in men whereas the age-adjusted incidence remained stable for women and increased by 2.6 per cent yearly for men. A study of 1189 patients who underwent surgical procedures showed that the annual number of embolectomy procedures increased 7.6 per cent for females and 8.6 per cent for males. The corresponding age-adjusted incidence rose annually by 3.0 per cent for women and by 7.5 per cent for men. The introduction of the Fogarty catheter and an increasing interest in vascular surgery may have contributed to the increasing rates of operations during the period of study. PMID- 1873719 TI - Realistic expectations for the patient with intermittent claudication. AB - To determine the natural history of intermittent claudication 112 patients were followed for a minimum of 5 years and a median period of 82 months. Thirty-seven patients (33 per cent) died during the study period. Myocardial infarction (44 per cent) and cerebrovascular disease (28 per cent) were the most common causes of death. Overall mortality rate was 8, 23 and 40 per cent, at 2, 5 and 8 years respectively. Initial ankle-brachial pressure index (ABPI) correlated with subsequent death. With an initial ABPI less than 0.5 death occurred in 20, 50 and 69 per cent at 2, 5 and 7 years respectively, compared with 5, 16 and 24 per cent respectively for those with an initial ABPI greater than or equal to 0.5 (P less than 0.0001). Of the survivors only 21 per cent had worsening claudication and 13 per cent progressed to critical ischaemia. Arterial bypass for limb salvage was required in eight patients and four limbs were lost during the study period. ABPI identifies a subgroup of claudicants with an extremely high risk of death from coronary and/or cerebral pathology. In this subgroup an aggressive approach to the correction of atherosclerotic risk factors, rather than emphasis on the peripheral vascular problem alone, may improve survival. PMID- 1873720 TI - Epidemiology of chronic venous ulcers. AB - A metropolitan population of 238,000 in Perth, Western Australia, was screened for chronic ulceration of the leg. Patients with a chronic leg ulcer and a venous abnormality comprised 57 per cent of all patients with a chronic leg ulcer, giving a prevalence of 0.62 per 1000 population. There was an increasing prevalence with age; 90 per cent of patients were 60 years and older. This group comprised 16.7 per cent of the population, and had a prevalence of 3.3 per 1000. Although chronic venous ulcers were more common in women there was no difference in age related prevalence. In 36 per cent of patients with a venous abnormality, there was at least one other aetiological factor contributing to chronic ulceration of the leg; 96 per cent had either a history of deep venous thrombosis or a condition known to predispose to deep venous thrombosis. PMID- 1873721 TI - Influence of phlebographic abnormalities on the natural history of venous ulceration. AB - Eighty-five limbs in 73 patients with a healed venous ulcer were assessed by ascending and descending phlebography, foot volume plethysmography and transcutaneous oxygen measurements. Forty-four limbs had post-thrombotic changes on ascending phlebography. In 24 (28 per cent) these extended into the femoral vein, while in 20 (24 per cent) only the calf veins were involved. In the 41 limbs (48 per cent) with normal deep veins on ascending phlebography, 11 had evidence of localized incompetence of the calf communicating veins, 14 had either long saphenous incompetence, deep vein reflux to the level of the knee or below, or both of these abnormalities, and 16 limbs had no phlebographic abnormalities. However all limbs had a decreased half volume refilling time on foot volume plethysmography. Limbs with post-thrombotic changes extending into the femoral vein were associated with a significantly longer history of ulceration and more ulcer recurrences than limbs with calf vein damage (P less than 0.05 for each) and limbs with normal deep veins (P less than 0.01 for each). However, these limbs did not have lower transcutaneous oxygen ratios or longer times to achieve ulcer healing. Ascending phlebography identified a group of limbs with extensive post-thrombotic changes in which there was a higher incidence of ulcer breakdown, but this was not associated with a delay in ulcer healing. PMID- 1873722 TI - Early computed colour echo Doppler imaging following renal transplantation. AB - Thirty patients with renal allografts were monitored for 15 postoperative days by colour-coded Doppler imaging and categorized as stable, rejection, acute tubular necrosis and cyclosporine toxicity. All forms of graft dysfunction showed significantly raised resistance (P less than 0.01) and pulsatility (P less than 0.01) indices (RI and PI, respectively). It was not possible to use Doppler imaging to differentiate the cause of graft dysfunction, but stable grafts in patients with high cyclosporin levels had significantly higher RI (P less than 0.04) and PI (P less than 0.04) than similar grafts in patients with cyclosporine levels in the therapeutic range. PMID- 1873723 TI - Preoperative clinical evaluation as a predictor of cardiac complications after infrarenal aortic reconstruction. AB - This paper analyses cardiac risk factors in 93 consecutive patients undergoing elective infrarenal aortic reconstruction over a 2 year period. During the perioperative or postoperative period, 26 patients sustained a total of 42 cardiac complications. Eight patients had myocardial infarction, 14 left ventricular failure and 15 arrhythmias. There were five cardiac-related deaths. Angina was the only statistically significant risk factor in predicting postoperative cardiac problems. A multivariate analysis identified a high-risk group of patients in whom cardiac complications after operation were common. PMID- 1873724 TI - Effects of two methods of endothelial cell seeding on cell retention during blood flow. AB - The potential benefits of endothelial cell seeding depend not only on effective cell attachment, but also on the ability of the cells to resist the stresses of blood flow. We have investigated the effect of different blood flow rates on immediately seeded grafts (SHORT) and also on preformed confluent monolayers formed by overnight incubation (LONG). Cells were labelled with indium and then exposed to either 100 or 200 ml/min of pulsatile blood flow. Cell retention was measured up to 120 min. At both flow rates the LONG seeding procedure gave significantly better cell retention than the SHORT method (P less than 0.01 at all times). There was no difference in cell retention between the two flow rates in the LONG group, but more cells detached at the higher flow rate in the SHORT group (P less than 0.01). We conclude that the new seeding method, using preformed confluent monolayers, significantly improves cell retention during blood flow. PMID- 1873725 TI - Major limb amputation in northern Nigeria. PMID- 1873726 TI - Isolated testicular pain: an unrecognized symptom of the leaking aortic aneurysm. PMID- 1873727 TI - Torsion of the spleen managed by splenopexy. PMID- 1873728 TI - Effect of fibrin sealant on the healing colonic anastomosis. PMID- 1873729 TI - Pulse oximetry: a new non-invasive assessment of peripheral arterial occlusive disease. PMID- 1873730 TI - Influence of methylprednisolone on the healing of intestinal anastomoses in rats. PMID- 1873731 TI - Influence of local hyperthermia on the healing of small intestinal anastomoses in the rat. PMID- 1873732 TI - Risk of peritonitis and fatal septicaemia and the need to defunction the low anastomosis. PMID- 1873733 TI - [Indications for cardiac surgery on the basis of noninvasive examination methods with major emphasis on echocardiography]. AB - Over the years 1983-1988 cardiosurgical procedures with extracorporeal circulation without catheterization of the heart were indicated in 191 patients, representing 19.8% of all the patients operated on at extracorporeal circulation (n--962). Indications for surgery were made on the basis of the clinical state of the patient and of the results of noninvasive methods, with main emphasis on echocardiographic findings. The close relationship between the methodological level of ultrasound diagnosis and the increasing number of patients operated on without preceding hemodynamic examination is documented (13% in 1983, 35% in 1988). With a few exceptions, noninvasive techniques provide a sufficient amount of relevant information definitely deciding on the indication for operation without catheterization in heart tumors and infective endocarditis, in about one half of the patients with dissecting aneurysm of the aorta and with deranged function of valvular prostheses, in one third of the patients with mitral defects, and in about one third of the patients with atrial septal defects. On the basis of their own results, the authors present the criteria for indicating cardiosurgical procedures without catheterization of the heart in the diagnoses studied. The diagnostic conclusion was confirmed by the operative finding in 99.5%. The obtained results are comparable with those reported by authors from abroad and demonstrate the significant medical and economic contribution. PMID- 1873734 TI - [Modulatory effect of glucans on the function of murine macrophages, NK-cells and lymphocytes]. AB - The particulate glucan (G1), soluble glucan preparations (G2 to G5, and G7) isolated from Saccharomyces cerevisiae, and glucomanan prepared from culture fluid after cultivation of Candida utilis (G6) were tested for their immunomodulatory activity in vivo and in vitro. In tests in vivo three soluble glucans (G3, G4, and G7) injected s.c. to mice in the dose of 10 mg/kg increased the cytotoxic activity of peritoneal macrophages. The influence of glucans on natural killer cells was without significance. The lymphoproliferative reaction of spleen cells to polyclonal mitogens was inhibited by all the preparations used with the exception of soluble glucan G2. The mitogenic effect of the preparations, co-stimulatory tests and direct cytotoxicity to cells of cell lines used in cytotoxicity assays were assessed in vitro. The transformation index of glucans in the study was increased according to the glucan and dose tested. Inhibition of the lymphoproliferative reaction measured by the co-stimulatory test for optimal concentration of Concanavalin A occurred in a wide range of doses for the preparations G1 to G6. The preparation G7 increased the incorporation of 3HTdR under the same conditions. The use of a suboptimal concentration of Concanavalin A revealed co-stimulatory activity of all the preparations tested. Assessment of the cytotoxic activity of peritoneal macrophages and of the activity of natural killer cells induced in vitro was complicated by the direct cytotoxicity of particulate glucan and soluble glucan G5 (carboxymethylglucan) for target cells (YAC 1, and YAC 1 and K 562 resp.). PMID- 1873735 TI - [History of knowledge about the structure of renal corpuscles and afferent arterioles]. AB - Some morphological findings obtained during the more than 300-year history of research into the fine structure of the kidney are presented in chronological order (discovery of renal corpuscles and their relationship to kidney arteries, elucidation of topographic relationships between glomeruli and tubules, discovery of specialized structure of juxtaglomerular segments of afferent arterioles). Gradual insight into the structure of the kidney was accompanied by elucidation of its function. Historical knowledge and findings demonstrated on simple drawings were verified in the present study by sophisticated methods of imaging, including transmission and scanning electron microscopy. The correspondence of the old schemes representing renal corpuscles (Malpighi, Bowman) with the actual morphological picture was established. PMID- 1873736 TI - [Anesthesia in Europe before 1939]. PMID- 1873737 TI - [Demography of anesthetists and recruitment needs in Germany]. PMID- 1873738 TI - Home study C.E.: RNs and unlicensed personnel. PMID- 1873739 TI - Art to science. PMID- 1873740 TI - Placement and replacement of restorations in a military population. PMID- 1873741 TI - Current research in preventive dentistry and its impact on the future of dental care. AB - To my mind, preventive dentistry has not changed all that much in the last 10 to 15 years. No miracle drug has come on the scene to prevent periodontal disease. There is no caries vaccine to eliminate dental caries. Interestingly, it has been the traditional technologies that have, given the advantage of time, proven their potential. The reality seems to have surpassed even our most optimistic expectations. But while we have learned how to effectively implement these technologies in many instances, the promotion of water fluoridation has lagged. Nevertheless, the improvements in oral health speak well of the work of our predecessors, who shaped the world of modern dental care. It is up to the profession to use existing preventive technologies to their best advantage and to devise even better preventive measures for the 20 per cent to 30 per cent of the population who are at highest risk of caries and periodontal disease. This paper has focused on some points of interest that have been published in the dental literature on preventive dentistry. Other issues represent concerns of the author. I invite comment and discussion on the topics and issues that were raised. Dialogue is healthy. PMID- 1873742 TI - Current research in implantology and its future impact. PMID- 1873743 TI - Dental lasers and science. AB - We have attempted to accomplish two purposes in this article. First, we have presented the case that extensive scientific investigation must form the base of our profession, that it must be an ongoing, continuous process and that laser dentistry must be developed through extensive scientific inquiry--as all of our treatment modalities should be. Second, we have presented many examples of the science involved in the development of laser dentistry. Lasers do have far reaching potential for application to dentistry. We, as a profession, must insist that such laser development is done properly, not foisted upon us based on anecdotal reports and incomplete research. PMID- 1873744 TI - Current research in diagnostic methods for assessing periodontal disease and its future impact. AB - A diagnostic test should be useful, ideally leading to a choice of treatment(s) that would confer benefits upon the patient. The many uses of diagnostic tests are listed in Table 2, but it should be recognized that no single test can be relied on exclusively. Combinations of various tests, especially those which detect infections and those which detect inflammation, would provide useful information for diagnosing and managing the patient's treatment. Certainly, any test or procedure can be considered useful if it facilitates the successful treatment of a patient's periodontal condition without a disproportionate increase in the cost to the patient or in his or her discomfort. By these criteria, many of the tests described in this paper are useful. The entry of these tests into clinical practice seems to be only a matter of time; their true usefulness is for the clinician to determine. PMID- 1873745 TI - Current research in operative materials and techniques and its future impact. PMID- 1873746 TI - The effects of the helium-neon laser on postsurgical discomfort: a pilot study. AB - It has been postulated that low-energy lasers (soft lasers) have analgesic capabilities. European investigators who have worked with these lasers have tried to explain this phenomenon as an interference with the mediation of the pain message and/or the stimulation of endorphin production. There does not appear, however, to be much well-controlled research to support these claims. This study has examined the effect of the helium-neon laser on post-surgical discomfort. Fifteen patients who had surgical removal of bilaterally symmetrical mandibular third molars were evaluated. Laser therapy was applied to one side of each patient's mouth with the other side serving as the control. A similar technique of application, without activation of the laser beam, was utilized on the control side. This study has demonstrated that the helium-neon laser (632.8 nanometre (nm) at 10 milliwatt (mW), when applied to the surgical site for three minutes immediately following third molar surgery, reduced postoperative pain on the day of surgery and on the first postoperative day. This finding was statistically significant. PMID- 1873747 TI - Labial endodontic access opening for mandibular incisors: endodontic and restorative considerations. AB - A labial access opening is suggested for endodontic treatment of mandibular incisors. This approach facilitates the identification and instrumentation of two canals, if present, and enhances achievement of complete obturation. More coronal tooth structure is preserved, enabling an optimum dowel core design for bracing the root. PMID- 1873748 TI - [Evaluation of maxillofacial injuries in a Quebec hospital]. AB - This article describes a study done on patients with maxillofacial traumas at the Hopital Christ-Roi in Quebec City. The patients were selected from those treated during the first three years after the Oral and Maxillofacial Surgery Department was set up. The hospital has 200 beds. In this study, the different epidemiological data and traumatic type are examined. Patient treatment is also discussed. The data analysis is supported by existing literature on the subject. PMID- 1873749 TI - Infant feeding practices and occlusal outcomes: a longitudinal study. AB - This study was undertaken to determine the relationship between infant feeding and occlusal outcomes. One hundred eight subjects born in 1983, whose mothers participated in the survey of infant feeding, took part in the 1988 survey of oral-health. A strong association (chi-square = 7.47; p = 0.006) was found between exclusive bottle-feeding and anteroposterior malocclusion. PMID- 1873750 TI - Developmental phases of sleep and motor behaviour in a cat mother-infant system: a time-lapse video approach. AB - The evolution of sleep patterns in developing kittens was studied using time lapse video technology and direct observation. The duration, frequency, and onset of the behavioural states and interactions of the cats were analyzed and then organized into phases that represent major changes in developmental structure during the first 6 weeks of kitten life. We have demonstrated that the kittens began exhibiting adult bi-cyclic sleep patterns on approximately Day 30 of development. During the 10-day period that preceded this consolidation of sleep pattern, REM sleep decreased by half, with a reciprocal increase in NREM sleep. These changes were coincident with an increase in kitten patterned motor behaviour and an increase in stimulation of the kittens by the mother during her bi-cyclic active periods. PMID- 1873751 TI - Some biochemical and behavioural aspects of the paradoxical sleep window. AB - It has recently been proposed that there is a vulnerable period of time following successful learning when paradoxical sleep (PS) is necessary for learning. This vulnerable time period has been called the PS window. In Experiment 1, the protein synthesis inhibitor anisomycin (ANI) was administered following shuttle avoidance training in the Sprauge-Dawley rat to coincide with the onset of an established PS window. Control groups received either saline or ANI either 3 hours before or 3 hours after the beginning of the PS window. Three hours after the injection, each group was retested. Then animals were immediately sacrificed, and whole brain biochemical analyses were done on levels of acetylcholine (ACh) and activity of acetylcholinesterase (AChE). Only the rats given ANI timed to coincide with the beginning of the PS window showed learning deficits. All ANI treated groups had less ACh and AChE activity. In Experiment 2, the ACh antagonist scopolamine (SCOP) was injected at the same times as in Experiment 1, and each of these groups had a corresponding saline control group as before. Retesting was done 1 day later; once again, the only group to show learning deficits was the group receiving SCOP timed to coincide with the PS window. Results suggested that the transmitter ACh plays an important role in learning/memory processes at the PS window. PMID- 1873752 TI - [Paradoxical sleep and information processing: exploration by inversion of the visual field]. AB - The purpose of this study was to test the potential relationship between REM sleep and information processing with inversion of the visual field. In the first experiment, four male subjects slept in the laboratory for two sessions of 6 consecutive nights: 2 adaptation nights, 2 nights of polysomnography, and 2 nights of dream collection. During the days preceding Nights 3, 4, 5, and 6 of each session, the subjects wore glasses which, during the second session, completely inverted (rotation of 180 degrees) their visual field. In a second experiment with four other male subjects, the order of conditions was reversed, and the experimental condition (visual inversion) was introduced a second time. When the data of the two experiments were combined, there was a significant (p less than .01) increase in the percentage of REM sleep from Nights 3 and 4 of the control condition to Nights 3 and 4 of the visual inversion condition, but there was no significant change in any of the other sleep stages. There was a significant decrease in horizontal (p less than .04) and vertical (p less than .005) REM density and in the density of vertical REM bursts (p less than .02). The increase in REM sleep supports the hypothesis that REM sleep contributes to information processing while the decrease in REM density suggests that this component of REM sleep may be involved in a homeostatic process of sensory input. PMID- 1873753 TI - The electrophysiological correlates of dream recall and nonrecall from stage 2 sleep. AB - This research examined the relationship between cortical activation, defined by electroencephalographic (EEG) measures, and the ability to recall dreams following awakenings from Stage 2 sleep. Period-analyzed EEG data from 40 subjects were examined for the preawakening, postawakening, and preawakening-to postawakening time intervals. Recall differed from nonrecall at the postawakening and preawakening-to-postawakening periods on measures of muscle activity and time spent in the sigma (12-16 Hz) frequency band. There were no distinctions in recall ability on EEG hemispheric asymmetry measures. Generally, the findings do not support the hypothesis linking increased recall ability to increases in cortical activation prior to awakening. However, the recall groups depicted a different pattern of arousal in their transition from sleep to wakefulness. PMID- 1873754 TI - [Paradoxical sleep: is it the guardian of psychological individualism]. AB - The brain is the sole organ of homeotherms that do not undergo cell division. We thus have to explain how certain aspects of psychological heredity (found in homozygotes twins raised in different surroundings) may persist for a whole life (psychological individuation). A definitive genetic programming during development (by neurogenesis) is unlikely due to the plasticity of the nervous system. That's why we have to consider the possibility of an iterative genetic programming. The internal mechanisms (synchronous) of paradoxical sleep (SP) are particularly adapted to such programming. This would activate an endogenous system of stimulation that would stimulate and stabilize receptors genetically programmed by DNA in some neuronal circuits. The excitation of these neurons during SP leads to oniric behaviours that could be experimentally revealed--the lists of these behaviours are specific to each individual and indirect data suggest a genetic component of this programming. Amongst the mechanisms allowing the iterative programming of SP, sleep is particularly important. Security--and hence the inhibition of the arousal system--is a sine qua non condition for genetic programming to take place. In that sense, sleep could very well be the guardian of dreaming. On the other hand, sleep seems to be necessary for the accumulation of energetic resources used by the cholinergic mechanisms of SP. The temporal modalities of SP (diachronic organization) are also discussed in relation to phylogenesis. Thus, the absence of SP in poikilotherms is explained by a continual neurogenesis in the adult. During ontogenesis in mammals, a stage of programming by neurogenesis (seismic sleep) precedes the appearance of SP so long as the programming system isn't functional. The presence, or absence, of rebound after SP deprivation is interpreted in terms of the existence, or non existence, of stress during SP suppression. An explanation is proposed to account for the absence of specific effects of SP deprivation in humans. In the same way somatic intraspecific variability is one of the conditions of evolution, it is proposed that one of the functions of SP is to maintain psychological variability in a given population. PMID- 1873755 TI - Behavioural response home monitoring of good and insomniac sleepers. AB - Can the fundamental differences in sleep structure known to differentiate good from insomniac sleepers (e.g., sleep length, sleep onset latency [SOL], number of sleep disruptions, etc.) be identified using a behavioural sleep/wake (S/W) monitor in the home? Sixteen women (8 good and 8 insomniac sleepers) enrolled in an introductory psychology course participated in a study of S/W patterns. They used a portable version of the Ogilvie and Wilkinson (1988) behavioural response (BR) system in their homes for 4 consecutive nights. Insomniacs had greater SOLs, less efficient sleep, and tended to have a greater number of arousals as compared with good sleepers. The data indicate that the behavioural system could be used as a diagnostic tool for in-home evaluations of disorders of initiating and maintaining sleep. PMID- 1873756 TI - Sleep physiology and psychological aspects of the fibrositis (fibromyalgia) syndrome. AB - Fibrositis (fibromyalgia) patients were compared with normal controls in terms of electrophysiology (EEG), self-report indicants of awakening, quality of sleep, behaviourally signalled awakenings, and Symptom Check List 90R (SCL-90R) scores. The results differentiated fibrositis patients from normal controls in terms of SCL-90R scores, with fibrositis patients showing significantly more psychopathology. Fibrositis patients had more alpha EEG sleep and less REM and Stage 1 sleep. They were better able to recall their behaviourally signalled awakenings the following morning and reported qualitatively less satisfying sleep than the normal controls. The alpha EEG sleep anomaly may reflect a vigilant arousal state during nocturnal sleep and result in the daytime experience of unrefreshing sleep, psychologic distress, that re-enforces the perpetuation of the sleep-related symptoms. PMID- 1873757 TI - REM periodicity under ultrashort sleep/wake cycle in narcoleptic patients. AB - Six narcoleptic patients were tested three times on the 13-min waking/7-min resisting sleep paradigm each time after a night of sleep in the laboratory. The three experiments were conducted after 10 days without any antinarcoleptic treatment or after 2 weeks of daily treatment with either methyl-phenidate or aniracetam. The results showed that patients had pronounced levels of diurnal sleepiness in all three experimental conditions with a midafternoon peak at around 1300-1500 hr and a nadir at around 1800 hr. Methyl-phenidate significantly reduced REM sleep and marginally reduced total sleep in comparison with the no treatment and aniracetam conditions. REM sleep in the 7/13 paradigm appeared cyclically with a dominant periodicity of 80 min/cycle. The cycles tended to be synchronized across patients and were unrelated to the temporal structure of total sleep. The present results support the continuation of the REM oscillator during brief periods of waking, but suggest that the REM periodicity is unrelated to Kleitman's BRAC model of arousal. PMID- 1873758 TI - Sleep in Alzheimer's disease and other dementing disorders. AB - It is estimated that up to 10% of the elderly population have clinically significant cognitive deficits. The neuronal pathologies that underlie the dementing disorders cause both cognitive dysfunction and disturbances in normal sleep/wake patterns. Here we report the changes in sleep/wake patterns seen with increasing severity of Alzheimer's disease, probably the most common dementing disorder. In addition, studies examining sleep/wake patterns in a number of other dementing disorders are reviewed. PMID- 1873759 TI - Field studies of sleep/wake patterns and performance: a laboratory experience. PMID- 1873760 TI - Asbestos: the turbulent interface between science and policy. PMID- 1873761 TI - Checklist for brain death. PMID- 1873762 TI - Statements from professional associations, specialty groups and consensus conferences: what editors expect. PMID- 1873763 TI - Stripping out pus in lactational mastitis: a means of preventing breast abscess. AB - OBJECTIVE: To determine whether manual stripping of pus from the breasts of women with lactational mastitis is effective in preventing the formation of breast abscesses. DESIGN: Case series (chart review). SETTING: Family practice in Montreal. PATIENTS: All (475) charts of patients with lactational mastitis were reviewed; 61 women were excluded because they already had a breast abscess. Most of the patients had been referred. OUTCOME MEASURES: Abscess formation, length of illness after treatment, rate of recurrence of mastitis, illness in the mother or infant within the 6 weeks after the mastitis and continuance of breast-feeding. MAIN RESULTS: The duration of symptoms before treatment was 1 to 56 (mean 5.3) days. In 9% of the cases both breasts were affected, and in 23% at least one episode of mastitis had previously occurred. The stripping technique was applied to all the patients. Pus was removed in 210 women; the remaining women were considered to have cellulitis. Only four patients (less than 1%) had breast abscesses. The mean length of illness after treatment was 7.2 days. The rate of recurrence was 14%. In all, 6% of the mothers and 9% of the infants became ill in the 6 weeks after the mastitis. Most (92%) of the patients continued to breast feed. CONCLUSIONS: The rate of abscess formation was considerably lower than the rates reported in the literature. Therefore, manual stripping of pus from the infected breasts of lactating women appears to be effective in preventing breast abscesses. PMID- 1873764 TI - A comprehensive health care directive in a home for the aged. AB - OBJECTIVES: To examine the use of and compliance with a new comprehensive health care directive by residents of a home for the aged and to determine the effect of the directive on the use of health care services. DESIGN: Descriptive study with a before-after design. SETTING: A home for the aged providing residential care to women. PARTICIPANTS: All 119 residents (ages 71 to 103 years, mean age 87.5 years). INTERVENTION: Introduction of a comprehensive health care directive and follow-up at 1 year. OUTCOME MEASURES: Residents' treatment choices, compliance with the directive, number of hospital admissions and length of hospital stay, number of deaths and places where deaths occurred. RESULTS: Ninety (76%) of the residents completed the directive. In the event of reversible life-threatening illness 34, 24, 11 and 21 residents requested supportive, limited, maximum and intensive care respectively. For irreversible illness the numbers were 75, 12, 3 and 0 respectively. In case of cardiac arrest 88% requested that cardiopulmonary resuscitation not be done. In the year before the introduction of the directive there were nine deaths, one in the home and eight in hospitals. In the year after there were 17 deaths, 11 in the home and 6 in hospitals. The mean length of hospital stay was significantly lower in that year than in the year before implementation (p less than 0.001). CONCLUSIONS: This innovative health care directive seems to be feasible, practical and well supported by residents, their families and health care professionals. Further studies are required to establish the generalizability and reproducibility of the data to other elderly people in institutions, to chronically ill patients and to the community at large. PMID- 1873765 TI - Alcohol and atherosclerosis risk. PMID- 1873766 TI - The history of caesarean section. 1935. PMID- 1873767 TI - Many Quebec MDs search for greener pastures as morale of province's doctors nosedives. PMID- 1873768 TI - U of T program aims to broaden skills of medical school's faculty members. PMID- 1873769 TI - A review of californium-252 neutron brachytherapy for cervical cancer. AB - Since 1976 a clinical trial has been conducted to test the feasibility, the potential, and to develop methods for using the neutron-emitting radioactive isotope, californium-252 (Cf-252), for the treatment of cervical cancer. A total of 218 patients were treated in the initial study period from 1976 until 1983. The trials initially treated advanced (Stages III and IV) cervical cancer patients using different doses and schedules; they were extended to include unfavorable presentations of Stages I and II because of favorable results in the initial trials. The authors began to treat patients with Stage IB bulky or barrel shaped tumors and the majority were treated with both radiation and hysterectomy. Actuarial survival was determined for Stage IB disease and was 87% at 5 years and 82% at 10 years. For those tested with preoperative radiation it was 92% at 5 and 87% at 10 years. For Stage II, it was 62% 5 years and 61% at 10. Survival 5 years after combined radiation and surgical therapy for Stage II disease was 68%. For Stage III, it was 33% at 5 years and 25% at 10. However, 5-year survival using the early neutron implant was 46% versus approximately 19% for delayed Cf-252 or cesium 137. Different schedules and sequences of neutrons and photons greatly altered outcome. Neutron treatment before external photon therapy was better for all stages of disease. Only about 5% of all patients developed complications after neutron therapy. No hematologic or mesenchymal second tumors were observed. Neutron brachytherapy was found to be very effective for producing rapid response and greatly improved local control of bulky, barrel, or advanced cervical cancers. The clinical trial identified and evolved schedules, doses, doses per session, and developed methods different from standard photon therapy but highly effective for local control and cure of cervical cancers of all stages. Clinical and radiobiologic understanding for the use of neutron therapy was greatly advanced by this trial. Future trials will focus on patients with advanced disease and will require evaluation of adjuvant chemotherapy studies and neutron enhancing chemicals. PMID- 1873770 TI - Amsacrine is safe and effective therapy for patients with myocardial dysfunction and acute leukemia. AB - The role of amsacrine in inducing remission in patients with cardiac disease and acute leukemia was evaluated. There were 17 patients with acute myelogenous leukemia (AML), six with acute lymphocytic leukemia (ALL), and one with biphenotypic leukemia. In this series of 24 patients whose disease had relapsed and who had reduced left ventricular ejection fraction, nine had a complete remission, seven with AML and two with ALL. In addition, four of six with newly diagnosed acute leukemia and reduced left ventricular ejection fraction also responded. Among nine patients who underwent endomyocardial biopsy, none had morphologic changes of sufficient degree to account for drug-induced heart failure. Patients with preexisting arrhythmias received amsacrine without incident if their serum potassium level was higher than 4.0 mEq/l at the time of drug administration. Amsacrine is safe and effective therapy for patients with acute leukemia and cardiac disease. PMID- 1873771 TI - Intensive chemotherapy induction followed by interferon-alpha maintenance in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. AB - In a pilot study, 32 patients with Philadelphia chromosome-positive chronic myelogenous leukemia were treated with intensive chemotherapy induction followed by interferon-alpha (IFN-A) maintenance. Intensive chemotherapy consisted of three cycles of daunorubicin 120 mg/m2 on day 1, cytarabine 80 mg/m2 daily for 10 days, vincristine 2 mg on day 1, and prednisone 100 mg daily for 5 days (DOAP). Maintenance therapy with IFN-A at a doses of 3 x 10(6) to 5 x 10(6) units/m2 daily was adjusted according to counts and toxicity. The outcome of patients was compared with a matched historic population of 64 patients treated with IFN-A alone. Overall, 60% of patients had a cytogenetic response (partial or complete) with induction chemotherapy, but only eight (25%) had a sustained cytogenetic response with IFN-A maintenance. After a median follow-up of 67 months, the 6 year survival rate of the 32 patients was 58%, compared with 36% for the matched historic group (P = 0.084). The incidence of lymphoid blastic transformation in the two groups was 25% and 48%, respectively (P = 0.10) and durable cytogenetic responses, 25% and 19%, respectively (P = 0.48). In summary, the addition of intensive chemotherapy induction to IFN-A maintenance does not improve the survival rate, incidence of lymphoid blastic transformation, or incidence of durable cytogenetic response compared with the results achieved with IFN-A therapy alone. PMID- 1873772 TI - Cure of early-stage Hodgkin's disease with subtotal nodal irradiation. AB - Ninety-four consecutive patients with Stage I or II Hodgkin's disease who presented supradiaphragmatically were treated with radiation therapy alone at the Mallinckrodt Institute of Radiology from January 1978 through December 1986. Fifty-two patients (55%) were staged pathologically, and 42 (45%) were staged clinically. The latter included lymphangiography and/or abdominal computed tomographic scan. Most patients with B symptoms and/or bulky disease were excluded from this series. Seventy-four patients were treated with subtotal nodal irradiation (mantle and periaortic fields). The spleen was treated if the patient had not undergone splenectomy. Twenty patients received mantle irradiation only. No patient received total nodal irradiation. All patients had an initial complete response. With a minimum follow-up of 7 months (median, 7.7 years; seven patients died before 3 years of follow-up, but all other patients had at least 3 years of follow-up), 81 patients (86%) remained disease-free. Six of 52 (12%) of the pathologically staged group had a relapse, as did seven of 42 (17%) of the clinically staged group (P = 0.68). Eight of 57 Stage I patients versus five of 37 Stage II patients had a relapse (P greater than 0.99). Analysis of disease free survival by age, histologic findings, sex, and sites of involvement did not predict relapse. The pelvis was the most common site of failure (nine patients, 10%). However, only three patients (3%) failed in the pelvis alone. These results indicate that patients who, after adequate clinical staging with selective use of staging laparotomy, are found to have Stage I and II Hodgkin's disease may be treated with subtotal nodal irradiation with a high rate of cure. PMID- 1873773 TI - A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high-grade extremity soft tissue sarcoma and an analysis of prognostic factors. AB - A prospective randomized trial was conducted to compare the cardiotoxic and therapeutic effects of doxorubicin (60 mg/m2 every 3 to 4 weeks) administered by bolus or 72-hour continuous infusion as adjuvant chemotherapy in 82 eligible patients after resection of high-grade soft tissue sarcoma of the extremity or superficial trunk. Cardiac toxicity, defined as a 10% or greater decrease in left ventricular ejection fraction as assessed by radionuclide cineangiography, was evaluated in 69 patients. Cardiotoxicity was seen in 61% of patients in the bolus treatment arm with the median doxorubicin dose of 420 mg/m2. Among patients who received continuous infusion, 42% had cardiotoxicity with a median dose of 540 mg/m2. The rate of cardiotoxicity as a function of the cumulative dose of doxorubicin was significantly higher in the bolus treatment arm (P = 0.0017). Two patients in each group had clinical congestive heart failure, with one cardiac death occurring in each. There was a trend toward a lower rate of metastasis (P = 0.19) and a significantly lower rate of death of disease (P = 0.036) for patients treated with the bolus dose. Cox model analysis identified three unfavorable characteristics for the rate of developing a distant metastasis: blood transfusion within 24 hours of operation (P less than 0.00001), tumor deep to the fascia and 5 cm or more in size (P = 0.0043), and a histologic subtype other than liposarcoma (P = 0.0002). The unfavorable effect of continuous infusion was not selected in the model (P = 0.16). Adjuvant chemotherapy for patients with soft tissue sarcoma is investigational. Furthermore, the impact of perioperative blood transfusion merits further study. PMID- 1873774 TI - A phase II trial of high-dose cisplatin and dacarbazine. Lack of efficacy of high dose, cisplatin-based therapy for metastatic melanoma. AB - Cisplatin and dacarbazine are used widely in the treatment of metastatic melanoma. To evaluate high-dose cisplatin and dacarbazine, 32 patients with metastatic melanoma were treated with cisplatin 50 mg/m2 and dacarbazine 350 mg/m2 daily for three days repeated at 28-day intervals. Their median age was 43.5 years (range, 25 to 73 years), and their median Karnofsky performance status was 80% (range, 70% to 100%). Measurable and evaluable disease sites (number of patients) included lymph nodes (22), lung (17), soft tissue (16), liver (13), bone (seven), spleen (four), adrenal gland (three), skin (three), and other sites (five). Patients received a median of two cycles of therapy (range, one to eight cycles). Thirty patients were evaluable for response. No complete responses were observed. Five patients had a partial response (17%; 95% confidence interval, 3% to 30%) for 16+, 12+, 7, 6.5, and 3 months. Responding sites of disease included lymph nodes (five of 22), lung (three of 17), and soft tissue (two of 16). Hematologic toxicity (Grade greater than or equal to 3) included neutropenia (16 of 32 patients, 30 of 90 cycles), thrombocytopenia (eight of 32 patients, 12 of 90 cycles), and anemia (five patients). Nine episodes of neutropenia and fever were seen in four patients; two had bacteremia. Nonhematologic toxicity (Grade greater than or equal to 3) included hypotension (two patients), nausea and vomiting (four), neuropathy (two), ototoxicity (four), and hypomagnesemia (nine). The low objective response rate and severe toxicity of this regimen preclude its standard use in patients with metastatic melanoma. A review of cisplatin-based therapy in metastatic melanoma suggests that there is no dose-response relationship. The use of high-dose cisplatin (greater than 100 mg/m2) in the treatment of metastatic melanoma is not recommended. PMID- 1873775 TI - High-dose cisplatin with dacarbazine and tamoxifen in the treatment of metastatic melanoma. AB - In an attempt to increase the antitumor effect of cisplatin (50 mg/m2) and dacarbazine (350 mg/m2), each repeated on days 1 to 3 every 4 weeks in patients with metastatic melanoma, tamoxifen was added to the regimen. Before the first course of chemotherapy, the patients received a loading dose of tamoxifen (100 mg orally twice a day for 7 days), followed by a maintenance dose of 10 mg orally twice a day and continued throughout the treatment. Aspirin (325 mg orally every other day) was administered at the same time as the tamoxifen in an attempt to reduce the risk of thromboembolic events. The activity of high-dose cisplatin with dacarbazine and tamoxifen was disappointing. Of 23 evaluable patients, only three responded--an overall response rate of 13% (95% confidence limits, 0% to 27%). These responses consisted of one pathologic complete remission in a patient with nodal metastases, one clinical complete remission in a patient with a very large pelvic mass, and one partial response in another patient with nodal metastases. The duration of responses was 12+, 4, and 4 months, respectively. These data do not support a significant interaction between tamoxifen and cisplatin or dacarbazine. Assuming that tamoxifen is important in the cisplatin, dacarbazine, and carmustine combination, as suggested by others, the most relevant interaction may be between tamoxifen and carmustine. PMID- 1873776 TI - A phase I, II study of high-dose 5-fluorouracil and high-dose leucovorin with low dose phosphonacetyl-L-aspartic acid in patients with advanced malignancies. AB - Twenty-eight patients with refractory advanced malignancies were treated with a 24-hour infusion of 5-fluorouracil (5-FU), leucovorin (LV), and N (phosphonacetyl)-L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable to assess toxicity and antitumor activity. The PALA was administered as an intravenous bolus over 15 minutes at a fixed dose (250 mg/m2) 24 hours before the start of the 5-FU and leucovorin infusions. Initially the dose of 5-FU was 750 mg/m2; this was increased incrementally to 2600 mg/m2. The LV was administered in a fixed dose of 500 mg/m2 concurrently with the 5-FU over a 24 hour period. This regimen was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among the dose-limiting toxicities. Others were hand-foot syndrome, hair loss of the scalp and eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. The maximum tolerated dose of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated with 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose reductions, but most received 5-FU at a dose of 2100 mg/m2. Twenty-three of 27 patients were treated previously. Eight patients had a partial response; five of these were treated previously. A complete response was observed in one patient with pancreatic carcinoma, previously untreated. The overall response rate for patients treated with 2100 or 2600 mg/m2 of 5-FU was nine of 18 patients (50%). Three of four previously untreated patients with pancreatic cancer responded to this treatment (two responded partially, and one had a complete response). One of three heavily pretreated patients with non-small cell lung cancer had a partial response as did a patient with breast cancer. Four of ten patients with colorectal cancer responded to the treatment (four partial responses), of whom three had been treated previously. PMID- 1873777 TI - Whole-abdominal irradiation for the management of gastrointestinal and abdominal manifestations of agnogenic myeloid metaplasia. AB - A patient with a long-standing history of agnogenic myeloid metaplasia developed weight loss and ascites secondary to gastric/small bowel infiltration and peritoneal implants of myeloid tissue. Moderate doses of radiation were very effective in controlling her gastrointestinal symptoms. In contrast to previous reports, clinical improvement after irradiation was a slow, gradual process, requiring 5 months for complete resolution of the patient's ascites. Hematologic suppression may be profound and careful attention to the rate of change in leukocyte and platelet counts is necessary to avoid severe toxicity. PMID- 1873778 TI - Inhibitory effects of the gastrin receptor antagonist (L-365,260) on gastrointestinal tumor cells. AB - A selective gastrin receptor (GR) antagonist, L-365,260 is bound to the GR on AR42J cells with a potency 7.5-fold less than G17 (50% inhibitory concentration [IC50] G17, 6 x 10(-9) mol/l; IC50 L365-260, 4.5 x 10(-8) mol/l). G17 is mitogenic for AR42J cells, as assessed by 75Se-selenomethionine uptake and L 365,260 at concentrations of 2.5 x 10(-6) mol/l and 2.5 x 10(-7) mol/l, (55X and 5.5 X the dose required to displace 50% 125I G17, respectively), and reduced optimal G17 stimulated mitogenesis in 75% of experiments. The basal growth of two human colon cancer cell lines, LoVo and C146 was reduced by L-365,260 (2.5 x 10( 7) mol/l) after 5 days of treatment to 44% and 64% of the control, respectively. However, inhibition was followed by a rebound of growth to control levels. The growth of AR42J xenografts in nude mice was increased by administration of G17 (10 micrograms/mouse/d, P less than 0.027). This increase was blocked by coadministration of oral L-365,260 (5 mg/kg/d, P less than 0.034). L-365,260 could be an important therapeutic agent in slowing the growth of GR-positive, G17 sensitive gastrointestinal tumors. PMID- 1873779 TI - Preoperative radiation therapy followed by extrafascial hysterectomy in patients with stage II endometrial carcinoma. AB - Seventy-four patients with Stage II endometrial cancer were treated by a combination of preoperative radiation therapy followed by extrafascial hysterectomy, bilateral salpingo-oophorectomy, and paraaortic lymph node sampling at the University of Kentucky Medical Center from 1967 to 1988. All patients had histologically confirmed endometrial cancer with involvement of the endocervix. The cell types and numbers of the tumors treated were as follows: adenocarcinoma, 58; adenoacanthoma, six; adenosquamous carcinoma, nine; and clear cell carcinoma, one. Preoperative radiation consisted of 4500 cGy external therapy followed by one intracavitary implant providing an additional 2000 cGy to point A. Surgery was done 4 to 6 weeks after completion of radiation therapy. Five patients (7.1%) had paraaortic lymph node metastases. Four were treated with extended-field radiation therapy and one with platinum-based combination chemotherapy. After treatment, the patients were followed at regular intervals from 2 to 22 years (mean, 5.4 years). Eleven patients (15%) had recurrent cancer, with the vagina and upper abdomen being the most common sites of spread. The estimated 5-year and 10-year disease-free survival rates of these patients are 88% and 76%, respectively. Cell type, depth of myometrial invasion, and lymph node status were the most important prognostic variables in the patients evaluated. These data confirm that the combination of preoperative radiation therapy and surgery produces excellent long-term survival in patients with Stage II endometrial cancer. PMID- 1873780 TI - The role of radical surgery in the management of radiation recurrent and large volume prostate cancer. AB - Twenty-two patients seen between 1975 and 1988 were analyzed who had surgical attempts to cure locally advanced prostate cancer by exenterative procedures or salvage surgery for radiation recurrent disease. Twelve patients (Group I) underwent either a salvage cystoprostatectomy or perineal prostatectomy for radiorecurrent disease, including three patients with a Kock continent urinary diversion done in combination with the salvage operation. Five of the 12 (41.7%) recurrent disease confined to the surgical specimen and 11 of 12 (91.7%) are alive at a mean follow-up of 49 months, including four patients (25%) with a completely negative serum prostate-specific antigen (PSA) value (less than 0.2 ng/dl). All perineal prostatectomy patients are continent, and two of the three Kock pouch patients are continent. Ten of the 22 patients (Group II) had a cystoprostatectomy or exenteration for locally advanced disease that the surgeon did not think was amenable to standard radical prostatectomy. Only one of these ten patients had negative surgical margins, capsule, and seminal vesicles. Nine are alive (although only one patient has no evidence of disease) at a mean follow up of 59 months. Morbidity was substantial with a 50% major complication rate including four patients requiring reoperation because of bleeding, abscess, bowel obstruction, or colostomy closure. Salvage procedures for radiorecurrent disease can be done safely, even with the inclusion of a continent diversion, and may be curative or provide survival benefit to carefully selected patients. Cystoprostatectomy or exenteration for locally advanced disease does not appear to be a curative endeavor for most patients and may be accompanied by significant morbidity. PMID- 1873781 TI - Elimination of clonogenic breast cancer cells from human bone marrow. A comparison of immunotoxin treatment with chemoimmunoseparation using 4 hydroperoxycyclophosphamide, monoclonal antibodies, and magnetic microspheres. AB - Autologous bone marrow transplantation (ABMT) may aid in the management of breast cancer, but is currently limited to patients without bone marrow metastases. In earlier studies, 5 logs of malignant clonogenic breast cancer cells could be eliminated from human bone marrow using a combination of chemoseparation with 4 hydroperoxycyclophosphamide (4-HC) and immunoseparation with monoclonal antibodies and magnetic microspheres. In this report the authors compare chemoimmunoseparation to treatment with immunotoxins for elimination of tumor cells from human bone marrow and for the preservation of normal precursors. Breast cancer cells from each of five cell lines were mixed with a tenfold excess of irradiated human bone marrow cells. Treatment with a combination of five immunotoxins reduced clonogenic tumor cell growth by 1.8 to 5.5 logs depending upon the cell line. With two of the five cell lines, clonogenic tumor cells were eliminated quantitatively. Using the CAMA-1 breast cancer cell line, treatment with multiple immunotoxins was compared with chemoimmunoseparation with 4-HC, a panel of five unconjugated monoclonal antibodies and magnetic microspheres. Chemoimmunoseparation eliminated 3.5 to 5.4 logs of malignant cells, while preserving 21% of Colony-forming unit-granulocyte-macrophage (CFU-GM) and 37% of burst-forming unit-erythrocyte (BFU-E). No clonogenic breast cancer cells could be detected. Immunotoxin treatment eliminated 2.2 to 5.4 logs of clonogenic breast cancer cells, but had no effect on the bone marrow precursors. In seven of ten experiments, however, clonogenic breast cancer cells remained after immunotoxin treatment. Consequently, treatment with 4-HC, multiple murine monoclonal antibodies and magnetic microspheres provided more consistent elimination of tumor cells than separation with immunotoxins, but was significantly more toxic for marrow precursors. PMID- 1873782 TI - Contribution of monocytes to the decreased lymphoproliferative response to phytohemagglutinin in patients with lung cancer. AB - Patients with lung cancer (LC) have a reduced T-cell proliferative response to phytohemagglutinin (PHA) compared with that of healthy individuals. This decreased response is a result of an inhibitory effect exerted by the monocytes as evidenced by: (1) a restoration to normal levels of the response to PHA when the peripheral blood mononuclear cells were depleted of adherent cells (AD) and (2) a dose-dependent inhibition of the response to PHA when the nonadherent cell population was co-cultured with increasing numbers of autologous AD cells. The addition of indomethacin to the cultures resulted in only a partial restoration of the response to PHA. Monocyte production of interleukin-1 from patients with LC in response to lipopolysaccharide was normal. These findings support the hypothesis that the AD cell population plays a major role in the low T-cell proliferative response to PHA in patients with LC. This suppressor effect is partially mediated by the prostaglandins released by the monocytes. PMID- 1873783 TI - A significant association of Ha-ras p21 in neuroblastoma cells with patient prognosis. A retrospective study of 103 cases. AB - To evaluate biologic characteristics of neuroblastoma, the authors examined the expression of Ha-ras gene (Ha-ras p21) in 103 primary tumors obtained at the time of diagnosis. Higher expression of the Ha-ras p21 in tumor cells showed a significant association with lower clinical stage of the tumor at diagnosis (chi square = 35.418, degrees of freedom [df] = 9, P less than 0.001) and survival of the patients (chi-square = 37.111, df = 3, P less than 0.001). Thirty-six (84%) of 43 patients with decreased Ha-ras p21 expression died of aggressive disease. The Ha-ras DNA was examined in the 32 tumors by Southern blot analysis. Neither augmentation nor deletion of the Ha-ras DNA was observed. Amplification of the N myc DNA was also examined in 43 cases in comparison with Ha-ras p21 expression. N myc amplification was detected in 12 (55%) of 22 patients who died, and 19 (86%) of the 22 patients showed a low expression of the Ha-ras p21 in tumor cells. Eighteen (86%) of 21 survivors showed a high expression of the Ha-ras p21. The expression of Ha-ras p21 was thought to be a clinically important marker for prognosis in children with neuroblastoma. PMID- 1873784 TI - Granulomatous angiitis of the spinal cord associated with Hodgkin's disease. AB - A 28-year-old man had a 5-month history of focal and generalized neurologic symptoms culminating in a thoracic myelopathy. Evaluation revealed granulomatous angiitis of the spinal cord in association with occult nodular sclerosing Hodgkin's disease. In previous reports, manifestations indicative of intracranial involvement have dominated the clinical presentation of granulomatous angiitis associated with Hodgkin's disease. Successful therapy for Hodgkin's disease may result in marked improvement of associated granulomatous angiitis, whereas the lack or failure of therapy results in a uniformly fatal outcome. Definitive antemortem diagnosis of granulomatous angiitis requires a biopsy of involved tissue. The cause of granulomatous angiitis, as well as the nature of its association with Hodgkin's disease, remains unexplained. PMID- 1873785 TI - Cervical implantation metastasis by endometrial adenocarcinoma. AB - A distinct type of cervical involvement by endometrial cancer is reported and termed cervical implantation metastasis. It is believed to result from implantation of endometrial cancer on the denuded endocervix after fractional dilatation and curettage (D & C). The histologic criteria for diagnosis are: (1) the cervical implantation metastasis must be imbedded in the endocervical epithelium or superficial stroma surrounded by an implantation site of inflammatory cells and granulation tissue (free-floating cancer cells above the cervical mucosa are not acceptable as implantation tissue), (2) the histologic findings of the cervical implantation metastasis must be similar to those of the endometrial adenocarcinoma in the uterine corpus, (3) the cervical implantation metastasis must be separate from the primary tumor with no evidence of direct extension, and (4) the cervical implantation metastasis should be surrounded by nonneoplastic endocervical glands with no transition between the two. Of the 176 patients who underwent fractional D & C before hysterectomy, nine (5%) were found to have cervical implantation metastasis. No patients had cervical implantation metastasis who did not undergo fractional D & C before hysterectomy. When stratified according to stage, grade, and myometrial invasion, there was no statistically significant difference in the recurrence rate between patients with or without cervical implantation metastasis. It appears that cervical implantation metastasis does not alter prognosis or require specific treatment. PMID- 1873786 TI - Maternal reproductive history and birth characteristics in childhood acute lymphoblastic leukemia. AB - Using birth-registration data, a case-control study was done to investigate the possible associations of childhood acute lymphoblastic leukemia (ALL) with birth characteristics and maternal reproductive history. The data included cases born and diagnosed in Minnesota since 1969. Matched analyses were conducted using 337 cases and 1336 birth year-matched controls. There was a statistically significant increased odds of ALL for birth to older (greater than 35 years) mothers (odds ratio (OR) = 2.14, 95% confidence interval (CI) = 1.28, 3.58), older fathers (OR = 1.62, 95% CI = 1.14, 2.30), mothers with at least a high school education (OR = 1.61, 95% CI = 1.05, 2.48), and larger intervals (greater than 5 years) between the birth of the proband and the preceding sibling (OR = 1.86, 95% CI = 1.12, 3.09). The increased odds of ALL for birth by Caesarean section approached significance (OR = 1.42, P = 0.06). No overall association was found for: gender, race, paternal education, fetal-loss history, birth order, prenatal care history, pregnancy complications, inducement of labor, multiple birth, gestational age, or birth weight. Age at diagnosis was an important effect modifier of some analyses. For cases diagnosed before age 2 years, there was a 2.7-fold increased odds of ALL if the last pregnancy had resulted in a fetal loss (P = 0.03). For cases diagnosed before age 4 years, birth weight greater than 3800 g was associated with a significant 2.05-fold increased odds of ALL. These data strengthen the hypothesis that prenatal events may play a causative role in childhood ALL, particularly in those cases diagnosed at a younger age. PMID- 1873787 TI - Lymphomas in University College Hospital, Ibadan, Nigeria. AB - The authors reviewed 508 cases of lymphoma seen during a 16-year period in University College Hospital, Ibadan, Nigeria. Hodgkin's disease was diagnosed in 95 (18.6%) patients, of which 45% had mixed cellularity type; 19%, lymphocyte predominance; 18%, nodular sclerosis; and 18%, lymphocyte depletion. The age distribution showed a single mode in the 11 to 25-year-old group. Male preponderance was more marked in children who made up 32% of the Hodgkin's disease patients. Non-Hodgkin's lymphoma occurred in 413 cases, of which 296 (71.7%) were high-grade malignancies. Burkitt's tumor occurred in 211 (41.5%) patients, 95% of whom were children, and showed a male to female ratio of 1.7:1. Compared with previous findings in this hospital, Hodgkin's disease showed increased proportions of the lymphocyte predominant and nodular sclerosing types. However, the characteristics of Burkitt's lymphoma did not change appreciably in the last three decades. PMID- 1873788 TI - Kaposi's sarcoma in a child after autologous bone marrow transplantation for non Hodgkin's lymphoma. AB - A case of Kaposi's sarcoma in a child with no serologic evidence of human immunodeficiency virus (HIV) infection is reported. A 7-year-old boy with Stage IV non-Hodgkin's lymphoma, after conventional chemotherapy, underwent autologous bone marrow transplantation (ABMT). Five months later he presented with supraclavicular mass and mediastinal enlargement. A bone marrow biopsy showed hypoplasia with no signs of the underlying disease, whereas the excised mass revealed a typical histologic pattern of Kaposi's sarcoma. The child is currently being treated with recombinant alpha-interferon (alpha-IFN) and regression of the disease has been achieved. PMID- 1873789 TI - Angiofollicular lymph node hyperplasia (Castleman's disease) in an adolescent female. Clinical and immunologic findings. AB - Angiofollicular lymph node hyperplasia is a heterogeneous disorder of unclear etiology and has a wide spectrum of systemic symptoms. This report describes a case of this disorder in a 15-year-old girl and examines the response of the primary mass, systemic symptoms, and alterations of selected immune parameters at diagnosis, as a result of steroid therapy and radiation therapy (RT). The patient had a 1-year history of growth failure, delayed puberty, and refractory iron deficiency anemia. Computed tomography scan showed a posterior mediastinal mass. Biopsy revealed angiofollicular lymph node hyperplasia of mixed hyaline-vascular and plasma cell type histologic type. Immunoperoxidase studies showed polyclonal B-cells, predominance of T-helper cells (CD4) over cytotoxic/suppressor T-cells (CD8), and the presence of natural killer (NK) cells. Southern blot analysis demonstrated germ line gene configuration for the T-cell antigen receptor and Ig heavy chain. The patient clinically improved with RT after failing to respond to steroids. Immunophenotyping of peripheral blood lymphocytes before therapy revealed a CD4:CD8 ratio of 0.8 with decreased numbers of circulating T-cells; this increased to 1.4 after steroid therapy. The patient's T-lymphocytes had no proliferative response to phytohemagglutinin (PHA) or concanavalin A (Con A) before RT. After RT, a small but significant mitogenic response to these reagents was noticed. The proliferative response to recombinant interleukin-2 (rIL-2) remained similar to that of control lymphocytes. Induction of second messenger signals by activation of protein kinase C (PKC) and elevation of free cytosolic calcium through the use of the phorbol ester, phorbol 12, 13-dibutyrate (PDBu), and ionomycin (Io) resulted in a strong proliferative response at diagnosis and after RT. In vitro cytotoxicity assays revealed diminished NK activity before and after therapy. Lymphokine-activated killer (LAK) activity remained comparable with that of control cells and was not affected by therapy. Before RT patient lymphocytes maintained cytotoxic capabilities after coincubation with rIL-2 and PDBu plus Io, whereas coincubation with these reagents abrogated cytotoxic function of normal cells. This case demonstrates a clinical response to RT as well as improvement in immune parameters. Intact signal transduction mechanisms through PKC activation and elevation of cytosolic calcium were also demonstrated in the circulating lymphocytes. PMID- 1873790 TI - Superior vena cava syndrome caused by an intrathoracic plasmacytoma. AB - A case of an extramedullary intrathoracic plasmacytoma causing superior vena cava syndrome is described. Review of the literature on intrathoracic plasmacytomas and superior vena cava syndrome revealed that no similar cases have been described to date. The initial presentation, management, and response to treatment are described. PMID- 1873791 TI - A population-based study on the incidence and survival rates of 3857 glioma patients diagnosed from 1953 to 1984. AB - Intracranial glioma was diagnosed during the patient's life and histologically verified in 3857 patients between 1953 and 1984 in Finland. Their survival up to the end of 1987 was analyzed, the follow-up being complete. The treatment was by operation in 1193 cases, radiation in 459 cases, both operation and radiation in 1486 cases, and neither operation nor radiation in 719 cases. The 1-year, 5-year, 10-year, and 15-year cumulative relative survival rates were 0.53, 0.29, 0.20, and 0.18, respectively. The newborn to 14-year-olds lost 56% of their life expectancy; the 15-year-olds to 44-year-olds, 71%; the 45-year-olds to 64-year olds, 88%; and the 65-year-olds to 99-year-olds, 91%. According to the model with the best fit in regression analysis the prognosis was significantly better among young, recently diagnosed patients who had undergone both operation and radiation. PMID- 1873792 TI - Prolactin and growth hormone levels in premenopausal women with breast cancer and healthy women with a strong family history of breast cancer. AB - Although both prolactin and growth hormone are believed to play roles in the development and growth of rodent mammary cancer, the role of these hormones in human breast cancer is uncertain. Under carefully specified conditions, serum levels of these hormones were determined by radioimmunoassay (RIA) and prolactin was determined by bioassay in 18 premenopausal women with breast cancer, 23 healthy women with a strong family history of breast cancer, and 39 healthy women with no significant family history of breast cancer. Parity was associated strongly with decreased prolactin levels, and increasing age was associated strongly with decreased growth hormone levels. After controlling for these variables, no differences in prolactin or growth hormone levels were found among the three groups of women. These data do not support roles for these RIA-measured hormones or bioassay-measured prolactin in premenopausal or familial breast cancer in omnivorous white women. PMID- 1873793 TI - CAncer Rehabilitation Evaluation System--short form (CARES-SF). A cancer specific rehabilitation and quality of life instrument. AB - The CAncer Rehabilitation Evaluation System (CARES) (CARES Consultants, Santa Monica, CA) a rehabilitation and quality of life instrument with well-documented reliability and validity, has been shortened. This report describes the development and psychometric properties of the new instrument, the CAncer Rehabilitation Evaluation System--Short Form (CARES-SF). The data from four existing samples of cancer patients demonstrate that the CARES-SF is highly related to the CARES (r = 0.98), has excellent test-retest reliability (86% agreement), concurrent validity with related measures, and acceptable internal consistency of summary scales (alpha = 0.85 to 0.61). In a new sample of breast cancer patients evaluated at three points in time (1 month, 7 months, and 13 months after diagnosis) the instrument appears to be sensitive to change and is highly related to the Functional Living Index--Cancer (FLIC), an existing quality of life instrument. The authors conclude that the CARES-SF has excellent potential as a quality of life instrument for use in clinical trials. PMID- 1873794 TI - Inhibition of protooncogene expression by antisense oligodeoxynucleotides: biological and therapeutic implications. PMID- 1873795 TI - Advantages of adoptive chemoimmunotherapy with polyethylene glycol-cultured, antigen-activated, tumor-infiltrated spleen cells for the complete eradication of lethal MOPC-315 plasmacytomas. AB - The incorporation of polyethylene glycol-6000 (PEG) into the culture media of tumor-infiltrated spleen cells (TISpC) and MOPC-315 stimulator tumor cells at a responder to stimulator cell ratio of 30/1 had been shown to lead to the appearance of CD8+ T-cells that were effective in adoptive chemoimmunotherapy (ACIT) of mice bearing a barely palpable MOPC-315 tumor (J. A. Wise, M. B. Mokyr, and S. Dray, Cancer Res., 49:3613-3619, 1989). Here we show that in the presence of substantially fewer added stimulator tumor cells (responder to stimulator cell ratio, 100/1), the inclusion of PEG in the cultures of TISpC also enhanced the appearance of cells that were highly effective in curing such mice by ACIT. Moreover, these PEG-cultured TISpC were more effective in ACIT than TISpC cultured in the presence of an optimal concentration of recombinant interleukin-2 (60 IU/ml). The potency of the tumor-eradicating activity of the PEG-cultured TISpC in ACIT was further illustrated by their ability to cause the complete regression of a large (20-22 mm) s.c. MOPC-315 tumor in conjunction with a dose of drug that by itself did not cause tumor regression. PEG-cultured TISpC that were effective against MOPC-315 tumor cells in an antigen-specific manner. In fact, PEG-cultured TISpC were more effective than recombinant interleukin-2 cultured TISpC, not only in ACIT, but also in their ability to lyse MOPC-315 tumor cells in vitro. Thus, a direct specific lytic activity against the tumor by cytotoxic T-lymphocytes is the apparent mechanism through which the complete regression of the large tumor burden is brought about by the PEG-cultured TISpC. Finally, we suggest that the incorporation of PEG to render ineffective lymphoid cells effective in ACIT may offer some advantages compared with the incorporation of recombinant interleukin-2 and may be suitable for protocols to generate human cytotoxic cells for cancer therapy when there are relatively low numbers of available tumor cells. PMID- 1873796 TI - Resistance patterns between cis-diamminedichloroplatinum(II) and ionizing radiation. AB - Cross-resistance between cis-diamminedichloroplatinum(II) (CDDP) and radiation resistance has been suggested from clinical and experimental data (C. T. Coughlin and R. C. Richmond, Semin. Oncol., 16: 31-43, 1989). To determine whether cross resistance patterns between both cytotoxic approaches exist, resistance against CDDP and ionizing radiation was induced separately in human ovarian cancer cells in a cross-over design. Subsequently sensitivity changes were determined for both treatment modalities. CDDP resistance was induced previously (P. J. Kuppen et al., Cancer Res., 48: 3355-3359, 1988), and resistant cells were grown at three different levels of CDDP:0 ng/ml; 250 ng/ml; and 500 ng/ml. Resistance with resistance factor (RF) 3.4 to 5.1 proved to be stable, since withdrawal of CDDP pressure for at least 6 mo did not alter resistance patterns. CDDP-resistant cells also demonstrated stable resistance against ionizing radiation, with RF ranging from 1.7 to 2.0. The resistance patterns could not be explained by differences in growth kinetics and DNA content. Resistance to ionizing radiation was induced in the same human ovarian cancer cells as used for CDDP resistance studies. Exposure with 1.5 Gy of intermittent irradiation during 6 mo, at time intervals of 48 h, resulted in cells which were able to grow under chronic ionizing radiation pressure. RF was 2.0; the resistance was lost after 6 mo of culturing without ionizing radiation pressure. With intermittent radiation doses of 0.5 and 1.0 Gy, no significant resistance could be induced. Cells intermittently exposed to 0.5, 1.0, and 1.5 Gy during 6 mo demonstrated increased sensitivity to CDDP, with 0.22 less than RF less than 0.43. Increased sensitivity was associated with proportionally increased formation of the platinum-DNA adducts. Differences in sensitivity for both ionizing radiation and CDDP were lost after 6 mo of culturing without radiation pressure; therefore, resistance toward ionizing radiation and, likewise, the increased sensitivity to CDDP, were judged to be unstable. In conclusion, data of the present study demonstrated that development of stable resistance to CDDP is associated with development of stable resistance to ionizing radiation in human ovarian cancer. Contrastingly, increased sensitivity to CDDP was found when resistance against irradiation was induced in the same cells. PMID- 1873797 TI - Hemin enhances the sensitivity of erythroleukemia cells to 1-beta-D arabinofuranosylcytosine by both activation of deoxycytidine kinase and reduction of cytidine deaminase activity. AB - The sensitivity of human myelogenous leukemia cells to 1-beta-D arabinofuranosylcytosine (ara-C) during induction of differentiation was examined. Treatment with hemin greatly increased the sensitivity of erythroid leukemia cells to ara-C. The enhancement of ara-C sensitivity by hemin was not as remarkable in nonerythroid leukemia cells. Hemin altered the metabolism of ara-C in human erythroleukemia K562 cells by reducing ara-C deaminase activity, increasing intracellular accumulation of ara-C, and activating the nucleoside kinases. These alterations may be involved in the enhancing effect of hemin on sensitivity of ara-C. These results suggest that some inducers of differentiation potentiate the antileukemic effect of ara-C on human erythroleukemia cells. PMID- 1873798 TI - Epidermal growth factor receptor-negative tumors are predominantly confined to the subgroup of estradiol receptor-positive human primary breast cancers. AB - A total of 725 human primary breast tumor biopsy samples were analyzed for epidermal growth factor receptor (EGFR) content, using a multiple-point EGFR assay standardized in accordance with the recommendations of the European Organization for Research and Treatment of Cancer Receptor Study Group. After the establishment of a lower cell membrane protein threshold of 0.2 mg of membrane protein per ml of assay buffer, the results of 27% (194 samples) of the EGFR determinations were excluded from the study because of insufficient assay membrane protein content. Of the remaining 531 breast tumor biopsy samples, 57% (302 samples) were shown to be EGFR positive by Scatchard analysis, with a median value of 40 fmol/mg of membrane protein. Of the breast tumor biopsy samples, 72% (380 samples) were estrogen receptor (ER) positive, and 65% (344 samples) were progesterone receptor (PgR) positive. EGFR positivity was found in 46% (173 of 380) of ER-positive and in 85% (129 of 151) of ER-negative breast tumor biopsy samples (P less than 0.0001), as well as in 49% (168 of 344) of PgR-positive and in 72% (134 of 186) of PgR-negative breast tumor biopsy samples (P less than 0.0001). Mean EGFR levels in ER-positive breast tumor biopsy samples were lower than they were in ER-negative ones, 40 +/- 31 (SD) against 72 +/- 55 fmol/mg of membrane protein (P less than 0.0001). Similarly, mean EGFR levels in PgR positive breast tumor biopsy samples were lower than they were in PgR-negative ones, 41 +/- 29 against 70 +/- 56 fmol/mg of membrane protein (P less than 0.0001). Both EGFR positivity and EGFR levels decreased with increasing steroid hormone receptor levels. A multivariate analysis showed only ER to be independently associated with EGFR. PMID- 1873799 TI - Inhibition of murine melanoma experimental metastasis by recombinant desulfatohirudin, a highly specific thrombin inhibitor. AB - Recombinant desulfatohirudin (r-hirudin), a highly specific inhibitor of thrombin, was examined to determine whether it would inhibit production of experimental lung metastasis by B16-F10 melanoma cells. In in vitro assays using mouse plasma, the high level of procoagulant activity in B16-F10 cells was significantly inhibited by r-hirudin in a dose-dependent manner. From 15 to 120 min after s.c. administration into C57BL/6 mice, r-hirudin (10 mg/kg) markedly prolonged clotting time in a time course pattern that directly correlated with that of blood distribution of 125I-labeled r-hirudin. The production of experimental lung metastasis by B16-F10 cells was significantly inhibited by r hirudin administered s.c. at time points ranging from 120 min before to 60 min after tumor cell inoculation with the most significant effects found in mice given r-hirudin 15 or 2 min before the i.v. injection of tumor cells. The organ distribution of [125I]IdUrd-labeled tumor cells demonstrated a clear difference in the lungs of mice treated with r-hirudin and the lungs of control mice, and these differences directly correlated with the number of lung tumor colonies found 3 weeks later. The inhibition of lung metastasis was not due to direct antitumor effects of r-hirudin. These results suggest that inhibition of coagulation events by r-hirudin significantly inhibit experimental lung metastasis during a critical time of 60 min after the entry of tumor cells into the circulation. PMID- 1873800 TI - Anomalous relationship between cisplatin sensitivity and the formation and removal of platinum-DNA adducts in two human ovarian carcinoma cell lines in vitro. AB - Two human ovarian tumor cell lines (SK-OV-3 and TR175), established from patients previously treated with alkylating agents, but not with cisplatin, expressed greater than 23-fold differences in cisplatin sensitivities in vitro. Cisplatin resistance in SK-OV-3 cells appeared to be associated with increased levels of glutathione and activities of glutathione reductase and glutathione peroxidase, with reduced catalase activity. No significant modification of drug uptake was noted and there was only marginally lower (16%) total platination of DNA, measured immunochemically, in these cells compared with the more sensitive TR175 cell line. SK-OV-3 cells, however, showed a significantly lower overall ability to remove drug-induced DNA damage, with an apparent inability to remove either the major DNA-DNA intrastrand cross-links in the sequence pGpG or the adducts cis Pt(NH3)2d(GMP)2, although by alkaline elution repair of DNA-DNA interstrand cross links was demonstrated. Significantly more of these interstrand cross-links were induced in these resistant cells. These data provide evidence for the involvement of altered glutathione metabolism and increased tolerance of certain types of drug-induced DNA damage as factors associated with the resistance phenotype of SK OV-3 cells. Paradoxically, however, although the highly cisplatin-sensitive TR175 cells had lower glutathione levels this was not reflected in significantly higher total platination of DNA, and these cells appeared to be proficient in removing all the major platinum-DNA adducts quantitated in this study. Mechanisms responsible for this relative sensitivity to cisplatin remain to be identified. PMID- 1873801 TI - Tumor necrosis factor gene expression is mediated by protein kinase C following activation by ionizing radiation. AB - Tumor necrosis factor (TNF) production following X-irradiation has been implicated in the biological response to ionizing radiation. Protein kinase C (PKC) is suggested to participate in TNF transcriptional induction and X-ray mediated gene expression. We therefore studied radiation-mediated TNF expression in HL-60 cells with diminished PKC activity produced by either pretreatment with protein kinase inhibitors or prolonged 12-O-tetradecanoylphorbol-13-acetate treatment. Both treatments resulted in attenuation of radiation-mediated TNF induction. Consistent with these results, we found no detectable induction of TNF expression following X-irradiation in the HL-60 variant deficient in PKC-mediated signal transduction. The rapid activation of PKC following gamma-irradiation was established using an in vitro assay measuring phosphorylation of a PKC specific substrate. A 4.5-fold increase in PKC activity occurred 15 to 30 s following irradiation, which declined to baseline at 60 s. Two-dimensional gel electrophoresis of phosphoproteins extracted from irradiated cells demonstrated in vivo phosphorylation of the PKC specific substrate Mr 80,000 protein at 45 s following X-irradiation. These findings indicate that signal transduction via the PKC pathway is required for the induction of TNF gene expression by ionizing radiation. PMID- 1873802 TI - In vivo and in vitro evaluation of the alkylating agent carmethizole. AB - Carmethizole, a novel bis-carbamate alkylating agent, was evaluated in vitro for potential mechanisms of interaction with DNA and in vivo for spectrum and degree of antitumor activity. In vitro, the concentration of carmethizole required to produce a 50% reduction in clonogenic cell survival was identical in O6 alkylguanine DNA alkyltransferase-positive and -negative human cell lines. The CHO cell line UV4, hypersensitive to mono- and bifunctional alkylating agents, was 37-fold more sensitive to carmethizole than normal cells. The UV5 cell line, which is not hypersensitive to cross-linkers, was 13-fold more sensitive to carmethizole than normal cells. Alkaline elution studies in L1210 cells exposed to carmethizole showed the presence of DNA-protein and DNA-DNA cross-links but not DNA strand breaks. These data suggested that the interaction of carmethizole with DNA produces monoadducts, DNA-protein, and DNA-DNA interstrand cross-links at several sites. In vivo, carmethizole was not cross-resistant with 1,3-bis(2 chloroethyl)-1-nitrosourea or Cytoxan as determined by testing against P388 leukemias resistant to the latter 2 agents. Carmethizole activity was similar to that of melphalan across the murine solid tumor panel, which consisted of B16 melanoma; colon adenocarcinomas 11a, 26, and 36; and the KHT sarcoma. Carmethizole, Cytoxan, and melphalan were all active and had comparable activity against the HCT-8 and MX-1 human tumor xenografts. The in vivo spectrum of activity and efficacy of carmethizole was similar to that of melphalan. PMID- 1873803 TI - Biological efficacy of boronated low-density lipoprotein for boron neutron capture therapy as measured in cell culture. AB - Low-density lipoproteins (LDLs) are known to be internalized by the cell through receptor-mediated mechanisms. There is evidence that LDLs may be taken up avidly by tumor cells to provide cholesterol for the synthesis of cell membranes. Thus, the possibility exists that LDLs may provide an ideal vehicle for the transport of boron to tumor cells for boron neutron capture therapy. A boronated analogue of LDL has recently been synthesized for possible application in boron neutron capture therapy. The analogue was tested in cell culture for uptake and biological efficacy in the thermal neutron beam at the Brookhaven Medical Research Reactor. It was found that boron concentrations 10 times higher than that required in tumors for boron neutron capture therapy were easily obtained and that the amount of uptake was consistent with a receptor-mediated binding mechanism. The measured intracellular concentration of approximately 240 micrograms 10B/g cells is significantly higher than that obtained with any other boron compound previously evaluated for possible clinical application. PMID- 1873804 TI - Direct radiolabeling of monoclonal antibodies with generator-produced rhenium-188 for radioimmunotherapy: labeling and animal biodistribution studies. AB - The use of 188Re from an alumina-based 188W/188Re generator has been investigated for antibody radiolabeling. It was found that, with simple labeling techniques, 188Re can be used immediately after elution. The direct radiolabeling of intact antibodies with 188Re is described. Lyophilized antibody preparations have been reconstituted with 188Re taken directly from the generator at specific activities of up to 15 mCi of 188Re per mg of antibody. Radiolabeling yields of 90 to 98% have been obtained, with the incorporation rate being dependent upon time and the relative concentrations of the reagents. It was determined that the conjugates were immunoreactive and stable when challenged by serum in vitro, with 188Re immunoglobulin G showing adequate resistance to reoxidation with no transfer of 188Re to serum protein. 188Re-antibody conjugates were shown to clear from the blood faster than the corresponding 131I-labeled antibody, giving rise to good tumor/nontumor ratios at 24 to 72 h postinjection, while serum samples taken from the animals have shown that the circulating 188Re remained bound to immunoglobulin G. The combination of the technologies of the 188W/188Re generator, the direct labeling methodology, and the use of single-vial lyophilized antibody makes the use of 188Re-radiolabeled monoclonal antibodies a simple and convenient method of cancer radioimmunotherapy with a beta-emitting radionuclide. PMID- 1873805 TI - Lipid peroxidation in rat AH-130 hepatoma cells enriched in vitro with arachidonic acid. AB - Tumor cells generally display low lipid peroxidation. A low content of polyunsaturated fatty acids in membrane phospholipids is a possible cause of their decreased susceptibility to lipid peroxidation. To investigate the importance of substrate availability in eliciting lipid peroxidation and to study cell viability in conditions of stimulated lipid peroxidation, AH-130 hepatoma cells were enriched with arachidonic acid. The enriched hepatoma cells showed increased mortality correlated with the increased incorporation of arachidonic acid in membrane phospholipids. When 0.5 mM arachidonic acid was added to hepatoma cells, this fatty acid reached a percentage content similar to that found in hepatocytes. Hepatoma cells enriched with this concentration were further incubated to determine their susceptibility to lipid peroxidation; mortality increased in parallel with increased thiobarbituric acid-reactive substance production. The highest mortality was in hepatoma cells treated with ascorbate/FeSO4. Mortality in normal cells was low, although they had a high production of thiobarbituric acid-reactive substances. The high capability of normal cells to metabolize the products of lipid peroxidation might explain the different viabilities of normal cells and hepatoma cells. It may therefore be possible to modify the composition of fatty acids of hepatoma cells in order to sensitize them to the toxic effect of prooxidant agents. PMID- 1873806 TI - Influence of cellular radiation sensitivity on local tumor control of human melanoma xenografts given fractionated radiation treatment. AB - The radiocurability of human melanoma xenografts was studied by treating tumors with multiple fractions of 2.0 Gy and using local tumor control at 180 days as end point. Three melanoma lines (E. F., G. E., M. F.) that are only weakly immunogenic in athymic nude mice (BALB/c-nu/nu/BOM) were selected for the study. The tumor radiocurability was found to differ considerably among the lines; the radiation doses required to achieve local control of 50% of the tumors irradiated (TCD50s; mean +/- SE) were 85.0 +/- 4.7 Gy (E.F.), 60.3 +/- 5.4 Gy (G.E.), and 99.3 +/- 5.7 Gy (M. F.). The radiation sensitivity in vitro of cells isolated directly from tumors also differed significantly among the lines. The TCD50 showed positive correlations with the surviving fraction after 2.0 Gy in vitro, the surviving fraction after two doses of 2.0 Gy (4-h interval) in vitro, and the surviving fraction after 4.0 Gy at a low dose rate (1.25 cGy/min) in vitro. Thus, the differences in tumor radiocurability among the lines were mainly a consequence of cellular differences in the capacity to repair radiation damage. Comparisons of measured TCD50s with theoretical TCD50s, calculated from cell surviving fractions measured in vitro after radiation treatment in vitro or in vivo, suggested that other tumor parameters, e.g., rate of population between radiation fractions, also had a significant impact on the TCD50. However, this study strongly supports the assumptions that the surviving fraction at 2.0 Gy in vitro is a useful parameter for prediction of clinical tumor radiocurability. PMID- 1873807 TI - Tumor promoter 12-O-tetradecanoylphorbol-13-acetate and sn-1,2-dioctanoylglycerol increase the phosphorylation of protein kinase C in cells. AB - Phosphorylation of protein kinase C (PKC) may be an important mode of regulation of this enzyme that plays a key role in mouse skin tumor promotion and in mammalian cell signal transduction. To investigate this possibility, PKC was specifically immunoprecipitated from Abelson murine leukemia virus-transformed normal rat kidney cells that had been metabolically labeled with [32P]orthophosphoric acid. The Mr 80,000 phosphoprotein that was specifically immunoprecipitated from Abelson murine leukemia virus-transformed normal rat kidney cells was found to be identical with purified rat brain PKC that had undergone cell-free autophosphorylation. This is based on comparisons of peptides generated by partial proteolysis with Staphylococcus aureus V8 protease by one dimensional polyacrylamide-sodium dodecyl sulfate gel electrophoresis and of tryptic peptides by reversed-phase high-pressure liquid chromatography. These data are consistent with phosphorylation of PKC in cells having occurred via autophosphorylation. The autophosphorylation of PKC was stimulated by treatment of C3H 10T1/2 cells with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate or sn-1,2-dioctanoylglycerol. Exposure of cells to 100 nM 12-O tetradecanoylphorbol-13-acetate for 15 min increased the phosphorylation of PKC by 5-fold in the particulate fraction, while treatment with 100 microM dioctanoylglycerol enhanced phosphorylation of PKC only by 2-fold. Phosphorylation of PKC in response to activation may have significance for altering the sensitivity of PKC to proteolytic down-regulation and/or to subsequent activation. PMID- 1873808 TI - Effect of urine on clonal growth of human bladder cancer cell lines. AB - Human urine contains growth factors; their physiological roles have not been established. The effect of normal human urine was examined in vitro on clonal growth of human bladder cancer cell lines. Clonal growth of HT-1376, HT-1197, and T24 was enhanced by five different fresh human urine samples from young men. Colony stimulating activity was detected in fractions with a molecular weight greater than 5000 by ultrafiltration. Sephadex G-50 gel chromatography identified two peaks of colony stimulative activity in HT-1376 with molecular weights of approximately 6000 and greater than 12,400, respectively; these two peaks also possessed immunoreactive epidermal growth factor (EGF) and NRK-49F transforming activities. The three bladder cancer cell lines possessed large quantities of EGF specific binding sites and exogenous EGF stimulated colony formation; EGF concentrations in human urine were found to be remarkably higher than those of exogenously added EGF which stimulated clonal growth of bladder cancer cell lines. Moreover, it was demonstrated that fresh urine samples (5%) incubated with anti-human EGF monoclonal antibody (KEM-10) neutralized completely the colony stimulating effects in HT-1376. These results indicate that fresh human urine stimulates clonal growth in human bladder cancer cell lines and that a major part of the activity is represented by urinary EGF. The data promote urinary EGF as a progressive agent of human bladder cancer. PMID- 1873809 TI - Defective provirus form of human T-cell leukemia virus type I in adult T-cell leukemia/lymphoma: clinicopathological features. AB - Human T-cell leukemia virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma (ATLL). To examine the relationship between defective HTLV-I proviruses and clinicopathological features, we examined 95 patients with ATLL showing clonal integration of HTLV-I proviral DNA; 77 patients (81%) showed 1 clonal band, 15 (16%) showed 2 clonal bands, and 3 (3%) showed 3 clonal bands. In addition, the defective proviral form was detected in 28 patients (29%): 23 (30%) of the 77 with 1 clonal band, 4(27%) of the 15 with 2 clonal bands, and 1(33%) of the 3 with 3 clonal bands. The numbers of clonal bands had no association with the presence of defective proviruses. We classified the 95 patients with ATLL into four types according to clinicopathological features (smoldering leukemia, chronic leukemia, acute leukemia, and lymphoma types). The distribution of patients with the defective form was not different among these four types. The HTLV-I genomes must have integrated into the human genome DNA and been deleted partially in the cells. The defective form was kept during the clinical stage. All patients with the defective form showed defect of the gag or/and env region. No patient had a defect of the pX region. These data suggest that the pX region of HTLV-I must have played an important role in ATLL genesis. PMID- 1873810 TI - Anti-GM2 monoclonal antibodies induce necrosis in GM2-rich cultures of a human glioma cell line. AB - The effects of four anti-GM2 monoclonal antibodies (DMAb-1, DMAb-2, DMAb-3, and DMAb-5) were studied on spheroid cultures from a human glioma cell line (D-54 MG) that is known to express high levels of GM2. The spheroids developed central necrosis 48 h after antibody exposures at concentrations greater than 6 micrograms/ml. No necrosis was found with antibodies that had been absorbed with GM2 prior to exposure or with unrelated cytotoxic antibodies. Immunohistochemistry showed that the necrosis started shortly after the antibodies were evenly distributed throughout the spheroids. Light and transmission electron microscopy revealed that a small portion of the cells, mainly in the periphery of the spheroids, was unaffected by antibody exposure. New monolayer cultures established from antibody-treated cells expressed a 50% lower GM2 content as shown by flow cytometry and determination of ganglioside content throughout at least 12 passages. Thus, the GM2-rich D-54 MG cell line has subpopulations of cells with lower GM2 content. Spheroids obtained from this subpopulation developed only minor necrosis after antibody treatment. These results show that GM2 antibodies cause severe necrosis of GM2-containing glioma cells in vitro, but the effect depends on the concentration of antigen, and a threshold number of GM2 molecules is required. PMID- 1873811 TI - Characterization of multidrug resistance by fluorescent dyes. AB - Fluorimetric techniques were used to examine accumulation of fluorescent probes by the P388 murine leukemia and an anthracycline-resistant subline, P388/Adriamycin(ADR), which expresses the multidrug-resistant phenotype. P388 could be differentiated from P388/ADR on the basis of fluorescence intensity measurements using 3 classes of cationic dyes that are sensitive to membrane potential differences: rhodamine esters, cyanines, and styrylpyridinium dyes. But fluorescence intensity differences were also observed with potential-insensitive dyes: zwitterionic rhodamines and an acridine orange derivative. In all cases, fluorescence intensity differences were caused by impaired dye accumulation, and could be eliminated by treatment of P388/ADR cells with verapamil. Moreover, fluorescence signals from 2 anionic potential-sensitive dyes, merocyanine 540 and a bis-oxonol, were identical in P388 and P388/ADR. None of these dyes could be used to delineate CCRF-CEM, a lymphoblastic leukemia of human origin from the CEM/VM-1 subline that exhibits a markedly atypical drug resistance pattern not based on an enhanced outward transport. But accumulation of both neutral and cationic dyes was impaired in CEM/VLB100, a subline of CCRF-CEM expressing mdr. These studies show that many cationic and neutral fluorescent probes are substrates for the enhanced outward drug transport system associated with P388/ADR cells, and cannot be used to probe membrane-potential differences in cells expressing the mdr phenotype. With several dyes, differences in fluorescence intensity were sufficient so that flow cytometry could be used to delineate P388 from P388/ADR and CCRF-CEM from CEM-VLB100. The latter technique may be useful for identifying malignant cell populations expressing multidrug resistance in patients with neoplastic disease. PMID- 1873812 TI - DNA double-strand breaks measured in individual cells subjected to gel electrophoresis. AB - Microscopic examination of individual mammalian cells embedded in agarose, subjected to electrophoresis, and stained with a fluorescent DNA-binding dye provides a novel way of measuring DNA damage and more importantly, of assessing heterogeneity in DNA damage within a mixed population of cells. With this method, DNA double-strand breaks can be detected in populations of cells exposed to X-ray doses as low as 5 Gy. The radiation dose-response relationship for initial formation of double-strand breaks was identical for cell lines irradiated in G1, regardless of their sensitivity to killing by ionizing radiation. However, for cells irradiated in S phase, DNA migration was significantly reduced. For Chinese hamster V79 cells, Chinese hamster ovary cells, WiDr human colon carcinoma cells, and L5178Y-R mouse lymphoblastoid cells, S-phase DNA appeared to be about 3 times less sensitive to X-ray damage than DNA from other phases of the cell cycle. However, for the very radiosensitive L5178Y-S cells, the migration of replicating DNA was reduced only slightly. For Chinese hamster V79 and Chinese hamster ovary cells, damage was repaired at a similar rate in all cells of the population, and 85% of the breaks were rejoined within 2 h after irradiation. The radiosensitive L5178Y-S cells repaired damage more slowly than V79 or Chinese hamster ovary cells; 2 h after exposure to 50 Gy, approximately 50% of the damage was still present. PMID- 1873813 TI - Localization of basic fibroblast growth factor and transforming growth factor beta 1 in the human mammary gland. AB - The presence and distribution of basic fibroblast growth factor (bFGF) and transforming growth factor beta 1 in benign and malignant human breast tissue were determined by immunohistochemistry and immunoblotting. Peroxidase staining of biopsy specimens using a polyclonal antibody to amino acids 1-24 of bFGF and a monoclonal antibody to whole recombinant bFGF showed this growth factor to be localized in the myoepithelial cells of the benign breast. Epithelial cells and stroma were negative. In hyperplasia and intraductal carcinoma in situ staining was still seen around the perimeter of enlarged ducts. In malignant biopsies, however, staining was seen only when benign elements were present or residual myoepithelial cells and basement membrane remained. Antigen absorption and immunoblotting confirmed the antibody staining to be specific for bFGF. Transforming growth factor beta 1 was shown, using the same techniques, to be located in the periductal and intraductal stroma, closely associated with epithelial or myoepithelial cells in the benign and malignant breast. The relative localization of these two growth factors in the mammary gland may be significant in the control of breast development and/or tumor formation and progression. PMID- 1873814 TI - Programmed death of nonproliferating androgen-independent prostatic cancer cells. AB - Androgen ablation induces an energy-dependent process of programmed death in nonproliferating androgen-dependent prostatic cancer cells which involves fragmentation of genomic DNA into nucleosomal oligomers catalyzed by nuclear Ca2+, Mg(2+)-dependent endonuclease enzymes activated following a sustained elevation in intracellular free Ca2+ (Cai). In contrast, androgen-independent prostatic cancer cells are not induced to undergo such programmed cell death by androgen ablation. One explanation for the inability of androgen ablation to induce programmed death of androgen-independent prostatic cancer cells is that such ablation does not result in a sustained elevation in Cai in these cells. This raises the issue of whether androgen-independent prostatic cancer cells can be induced to undergo programmed death if an elevation in the Cai is sufficiently sustained by nonhormonal means. To test this possibility, androgen-independent, highly metastatic Dunning R-3327 AT-3 rat prostatic cancer cells were chronically exposed in vitro to the calcium ionophore ionomycin to sustain an elevation in their Cai. These studies demonstrated that an elevation of Cai as small as only 3 6-fold above baseline can induce the death of these cells if sustained for greater than 12 h. Temporal analysis demonstrated that the death of these cells does not require cell proliferation and involves Ca(2+)-induced fragmentation of genomic DNA into nucleosome-sized pieces as the commitment step in this process. These results demonstrate that even nonproliferating androgen-independent prostatic cancer cells can be induced to undergo programmed cell death if a modest elevation in the Cai is sustained for a sufficient time. These observations identify Cai as a potential target for therapy for androgen independent prostatic cancer cells. PMID- 1873815 TI - Frequent down-regulation of major histocompatibility class I antigen expression on individual micrometastatic carcinoma cells. AB - An astoundingly high frequency of micrometastatic cells have been found in bone marrow aspirates of patients with colon carcinomas (G. Schlimok et al., J. Clin. Oncol., 8:831-837, 1990), although these tumors very rarely metastasize to the skeleton. This observation has raised questions about the malignant potential of such cells. In a first attempt to characterize this potential, we have assessed the expression of major histocompatibility complex (MHC) class I antigens on bone marrow micrometastases, inasmuch as down-regulation of these molecules is a potential mechanism to escape from MHC class I-restricted lysis by cytotoxic T cells. The two groups of cancer patients compared were those with tumors known to rarely (stomach and colon cancer) or frequently (breast cancer) manifest skeleton metastases. Bone marrow aspirates taken from these patients were probed for individual disseminated tumor cells using the immunoalkaline phosphatase technique with monoclonal antibody CK2 to the epithelial differentiation antigen cytokeratin 18 (CK-18), as described previously (G. Schlimok et al., Proc. Natl. Acad. Sci. USA, 84:8672-8676, 1987). Specimens containing CK18-positive cells were colabeled with monoclonal antibody W6/32 directed to a framework (or nonpolymorphic) antigenic determinant of MHC class I heavy chains associated with beta 2-microglobulin. W6/32-positive CK-18-positive cells could be detected in 25 of 54 patients (46.3%) with significantly higher incidences in 26 breast cancer patients (61.9%) as compared to 28 patients with carcinomas of the stomach and colon (27.3 and 29.4%). Independent from the origin of the primary carcinoma, the incidence of W6/32-negative CK18-positive cells was positively correlated to both the differentiation grade of the primary tumor (P less than 0.05) and appeared to be linked to the occurrence of regional lymph node metastases (statistically not significant) determined by conventional histological examination. The present results demonstrate for the first time that down-regulation of MHC expression on individual micrometastatic cells correlates to the differential pattern of metastasis obtained by comparing breast and gastrointestinal carcinomas. This finding together with the suggestive link to clinical risk factors supports the significance of reduced MHC class I expression for the survival of residual metastatic cells which is a major determinant of prognosis for patients with solid tumors. PMID- 1873816 TI - Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles. AB - Evidence supporting a broad role for the inactivation of the p53 gene in human tumorigenesis has been provided by studies showing that the p53 gene is mutated in many human cancers. In this study, we report on the mutational status of the p53 gene in prostate cancer cells and provide functional evidence that the wild type p53 gene may have a role in suppressing prostatic tumorigenesis. Sequence analysis of exons 5-8 of the p53 gene reveals that three of five prostate cancer cell lines (TSUPr-1, PC3, DU145) contain mutations which alter the amino acid sequence of this most highly conserved portion of the gene. One of two primary prostatic cancer specimens examined also contained a mutation in this region. Transfection of the wild-type p53 gene versus a mutated p53 gene into two cell lines with p53 mutations results in reduced colony formation. Wild-type p53 gene expression is apparently incompatible with continued growth of these tumor cells inasmuch as none of the colonies which formed after wild-type transfections retain the transfected p53 sequences. Immunocytochemical data indicate that prostate carcinoma cells expressing the transfected wild-type p53 gene are growth arrested because they exhibit a reduced level of thymidine incorporation into DNA. This study is the first report of p53 gene mutations in prostate cancer cells and suggests a functional role for the p53 gene in suppressing prostatic tumorigenesis. PMID- 1873817 TI - Infrequent p53 gene mutations in medulloblastomas. AB - Cytogenetic and molecular studies of medulloblastomas have demonstrated frequent loss of sequences from the short arm of chromosome 17, possibly implicating loss or inactivation of the p53 tumor suppressor gene. We amplified exons 5 through 8 of the p53 gene by the polymerase chain reaction technique. These segments, which encompass the regions usually mutated in human tumors, were sequenced to search for p53 mutations in 12 medulloblastoma tumors, 8 xenografts, and 3 permanent cell lines. Mutation of the p53 gene was found in only 1 of 3 cell lines tested and in none of the xenografts or primary tumors studied. Our results suggest that p53 is mutated in an unusual way or that a second tumor suppressor gene on the short arm of chromosome 17 is involved in the pathogenesis of medulloblastoma. PMID- 1873818 TI - Singleness my choice. PMID- 1873819 TI - Singleness: a very viable option. PMID- 1873820 TI - Effects of basin baths, tub baths, and showers on cardiovascular responses in 51 health men and women. AB - Heart rate and blood pressure during rest and bathing are generally lower in healthy individuals than in hospitalized patients. However, medications can exaggerate or attenuate patients' responses. Heart rate and blood pressure are highest during showering and lowest during basin baths in both patients and healthy subjects, but the differences among the three types of bathing are not clinically dramatic. In addition, the vigor of the activity can be easily controlled; hospitalized patients naturally conserve effort and move more slowly and deliberately than healthy individuals. A tachycardic response to bathing seems to be common in both healthy subjects and hospitalized patients. Careful control of water temperature and heart rate monitoring during bathing appear to be indicated when hospitalized cardiac patients bathe. Comparison of responses to sitting and standing showering would be worthwhile. The findings of this study help delineate the typical cardiovascular responses of healthy adults to three methods of bathing. The findings also emphasize gender differences and the importance of studying both men and women. Only by determining normal responses in men and women can abnormal responses be recognized. More study on cardiovascular responses to bathing and other common activities in both healthy and sick persons is clearly needed to better describe, explain, predict, and control responses to activity and to build a scientific foundation for activity prescription and restriction. PMID- 1873821 TI - Streptococcal cell wall-induced arthritis and adjuvant arthritis in F344----Lewis and in Lewis----F344 bone marrow chimeras. AB - Streptococcal cell wall (SCW)-induced arthritis and adjuvant arthritis (AA) are rat models for chronic, erosive polyarthritis. Both models can be induced in susceptible Lewis rats, whereas F344 rats are resistant. In AA as well as in SCW arthritis, antigen-specific T lymphocytes have been demonstrated to be crucial for chronic disease. In this communication we describe our studies to probe the cellular mechanism responsible for the difference in susceptibility of Lewis and F344, using bone marrow chimeras. By transplanting bone marrow cells from F344 into lethally irradiated Lewis recipients, Lewis rats were rendered resistant to SCW arthritis induction. F344 rats reconstituted with Lewis bone marrow, i.e., Lewis----F344 chimeras, develop an arthritis upon SCW injection. For AA comparable results were obtained. These data suggest that both resistance and susceptibility to bacterium-induced chronic arthritis are mediated by hemopoietic/immune cells and that the recipiental environment does not influence the susceptibility to chronic joint inflammation. PMID- 1873822 TI - Experimental murine hypersensitivity pneumonitis. AB - To establish a model of experimental hypersensitivity pneumonitis (EHP) in mice and to examine the influence of genetic background on the pulmonary inflammatory response to Micropolyspora faeni, we determined the responses of C57BL/6, SJL/J, and C3H/HeJ mice to intratracheal (i.t.) injections of M. faeni. Recipient animals received lymph node cells (LNC), peritoneal exudate cells (PEC), and spleen cells (SC) from sensitized mice cultured in vitro with M. faeni. Controls included serum containing anti-M. faeni antibody; uncultured SC from M. faeni sensitized donors, and M. faeni-cultured SC from ovalbumin (OA)-sensitized donors. Recipients were challenged i.t. with M. faeni or normal saline 48 hr after the cell or serum transfer. We developed a model of EHP in mice. Increasing amounts of i.t. M. faeni were associated with increasing extent of pulmonary inflammation with no difference between the mouse strains. There was substantial increase of the extent of pulmonary abnormalities in the animals receiving cultured SC. The number of transferred cells and the M. faeni concentration correlated with the extent of pulmonary histologic abnormalities. Cultured PEC and LNC could transfer EHP in C3H/HeJ mice only. Serum containing anti-M. faeni antibody, cultured SC from OA-sensitized donors, and noncultured SC from sensitized donors could not transfer EHP. We conclude that it is possible to adoptively transfer EHP. PMID- 1873823 TI - Characterization of effector functions of v-raf/mil- and v-myc-transformed murine splenic macrophage cell lines. AB - We have characterized several of the cytocidal effector functions of a series of cell lines derived by recombinant retroviral transformation of individual clones of C3H/HeJ mouse splenic macrophages. The three cell lines described in this report (4.01, 4.07, 4.14) all expressed equivalent tumoricidal activity against P815 tumor target cells. However they differed in their high avidity binding of tumor cells (4.01 = 4.14 greater than 4.07), as well as in the killing of Leishmania major (4.01 = 4.07 greater than 4.14), the expression of antibody dependent cellular cytotoxicity against chicken erythrocytes (4.14 greater than 4.01 greater than 4.07), and finally, in the tumor-stimulated release of tumor necrosis factor-alpha (4.01 = 4.14 greater than 4.07). The stable and restricted expression of distinct effector functions among these three cell lines makes them particularly valuable as models for establishing the precise mechanisms by which cytocidal functions are effected. In addition, they should also prove of value in understanding the basis for macrophage functional diversity. PMID- 1873824 TI - Liposome adjuvanticity: influence of dose and protein:lipid ratio on the humoral response to encapsulated and surface-linked antigen. AB - The humoral response to bovine serum albumin either encapsulated in or surface linked to liposomes was studied as a function of dose and protein:lipid ratio. Total immunoglobulin, total IgG, IgM, and the G isotypes, IgG1, IgG2a, and IgG3 were measured during the plateau phase of production after a boosting injection. Although the adjuvant character of liposomes was confirmed regardless of the mode of antigen association, important differences in the response to the two types of liposomal formulations were observed. Our results suggest that surface-linked antigen stimulates the immune system at lower doses than its encapsulated counterpart, is more sensitive to the protein:lipid ratios, and can stimulate the production of particular immunoglobulin isotypes in controlled conditions. Our data support the idea that different pathways of processing are utilized by the two forms of liposomal antigen. PMID- 1873825 TI - Interleukin-1 is a mucus secretagogue. AB - Explant cultures of mouse duodenum were used to show that interleukin-1 (IL-1) causes release of mucus from epithelial goblet cells. Our experiments made use of a newly described enzyme-linked lectin assay (ELLA) which employs enzyme conjugated soybean agglutinin to detect mucus glycoproteins secreted from explant cultures of mouse duodenum. Supernatants from cultures of lipopolysaccharide stimulated peritoneal macrophages as well as partially purified rabbit alveolar macrophage-derived IL-1 and human rIL-1 beta all induced mucus release in a rapid and dose-dependent fashion. This observation may be important for investigating a link between the immune response and mucus hypersecretion from inflamed intestinal mucosa. PMID- 1873826 TI - Functional equivalence of cryptococcal and haptene-specific T suppressor factor (TsF). I. Picryl and oxazolone-specific TsF, which inhibit transfer of contact sensitivity, also inhibit phagocytosis by a subset of macrophages. AB - Monoclonal and conventional cryptococcal-specific T suppressor factors (TsF) (also called TsFmp) depress phagocytosis by a subset of macrophages, while picryl and oxazolone-specific TsF depress the passive transfer of contact sensitivity. This paper shows that these haptene-specific TsF also inhibit phagocytosis by a subset of macrophages and, using this assay, that the anti-haptene TsF resemble the anti-cryptococcal TsF in five respects: (i) the need for reexposure to specific antigen to trigger the release of TsF; (ii) genetic restriction in action; (iii) possession of an antigen-binding site; (iv) expression of I-J determinants; and (v) inactivation by reduction and alkylation. Purification of the anti-picryl TsF by sequential affinity chromatography indicates that the inhibition of phagocytosis is due to the TsF itself and not to a TsF-antigen complex. The TsF inhibits phagocytosis by a direct action as macrophages treated with TsF and exposed to antigen do not release a second factor which inhibits phagocytosis. These results and those of the accompanying paper indicate that the anti-cryptococcal and anti-haptene TsF are functionally equivalent, antigen specific suppressor factors. PMID- 1873827 TI - Functional equivalence of cryptococcal and haptene-specific T suppressor factor (TsF). II. Monoclonal anti-cryptococcal TsF inhibits both phagocytosis by a subset of macrophages and transfer of contact sensitivity. AB - Monoclonal anti-cryptococcal TsF (which inhibits phagocytosis by macrophages) and anti-picryl TsF use the same two circuits to block the transfer of contact sensitivity (CS). Both arm macrophages which then release a macrophage suppressor factor (MSF) when exposed to antigen. This MSF depresses the transfer of CS. The evidence suggests that a single molecular species of TsF (MW ca. 70 kDa), which bears an antigen-binding site and I-J determinant, is responsible for MSF production and inhibition of phagocytosis. Anti-cryptococcal TsF also arms the T acceptor cell which then releases nsTsF-1 after triggering with a specific antigen (SCPA). This nsTsF-1, which depresses the transfer of contact sensitivity, was authentic, as shown by its I-J positivity (in contrast to MSF) and its role in the production of nsTsF-2. As anti-picryl TsF also inhibits phagocytosis, it was concluded that anti-cryptococcal TsF, originally detected by the inhibition of phagocytosis, and anti-picryl TsF, originally detected by inhibition of CS, are functionally equivalent. PMID- 1873828 TI - GM-CSF augments the immunosuppressive capacity of neonatal spleen cells in vitro. AB - Addition of exogenous granulocyte-macrophage colony stimulating factor (GM-CSF) to cultures of adult murine spleen cells with sheep red blood cells (SRBC) results in an augmented plaque forming cell (PFC) response. The influence of GM CSF on the ability of neonatal spleen cells to suppress the anti-SRBC plaque forming response of adult spleen cells was tested by adding GM-CSF to cultures of neonatal and adult spleen cells. The suppressive capacity of the neonatal spleen cells was augmented by exogenous GM-CSF. The augmented suppression of the neonatal spleen cells was dependent on a G-10 adherent population since the addition of GM-CSF to cultures containing G-10 passed neonatal spleen cells resulted in an augmented PFC response and not suppression. Neonatal splenic glass adherent cells were also capable of suppressing the response. Neonatal spleen cells or purified neonatal glass adherent spleen cells cultured in the presence of GM-CSF had markedly increased levels of PGE2 in the culture supernatant. Neonatal spleen cells cultured with GM-CSF had increased numbers of morphologically identifiable macrophages after 48 hr of culture. Both irradiation and G-10 passage of the neonatal spleen diminished the numbers of macrophages formed in response to GM-CSF, and both of these manipulations resulted in reversal of suppression in response to GM-CSF. Thus, the augmented suppressive capacity of neonatal spleen cells in response to GM-CSF is probably mediated by its ability to drive monocyte to macrophage differentiation as well as increase the suppressive capacity of the existing neonatal splenic macrophages by increasing their production of PGE2. PMID- 1873829 TI - Ocular immunology: on the birth of a new discipline. PMID- 1873830 TI - [Evaluation of acceleration of fetal sounds in intrauterine hypoxia]. PMID- 1873831 TI - [Prognostic significance of detection of an anechoic space in the placenta (haemangioma placentae) in intrauterine fetal development]. PMID- 1873832 TI - [Personal experience with a single prophylactic dose of cephalosporin in cesarean sections]. PMID- 1873833 TI - [Results of ultrasonic detection of congenital developmental defects in fetuses at the Brno Gynecology-Obstetrical Clinic]. PMID- 1873834 TI - [The psychological status of women during the climacteric]. PMID- 1873835 TI - [Use of quinolones in the treatment of infections in gynecology]. PMID- 1873836 TI - [Active management of the 2d stage of labor versus physiological management of the 2d stage of labor]. PMID- 1873837 TI - [New findings on regulation of the endocrine function of the placenta]. PMID- 1873838 TI - [Comments on the moral question of abortion]. PMID- 1873839 TI - [Cytodiagnosis throughout the world and the work of the cytology section in Czechoslovakia]. PMID- 1873840 TI - [Submicroscopic structure of amniotic fluid cells]. AB - Submicroscopic examination of amniotic fluid cells in the second trimester of pregnancy revealed that the cells are from the morphological aspect a very heterogeneous population, comprising vital and degenerated cells the ultrastructure of which rules out the possibility of cultivation of cells of foetal as well as of maternal origin. As to degenerated cells, the authors identified circular cells with a granular cytoplasm and nucleus originating from the urogenital or digestive tract of the foetus. Furthermore cells with a process and segmented or fragmented pycnotic nucleus derived from granulocytes and macrophages of maternal origin. Also circular cells of the periderm with short microvilli and advanced regressive changes of the nucleus and cytoplasm are degenerated. Among non-vital elements also anuclear completely keratinized cells of the stratum corneum originating from the skin of the maternal abdomen can be included. As to vital elements, the amniotic fluid contains cells of the amniotic ectoderm which are large, have numerous microvilli, a dense margin and a network of filaments in the cytoplasm. They are the most numerous cells. Other vital elements in amniotic fluid include granulocytes and macrophages with a typical ratio of lyzosomes. Both are considered elements of maternal origin. Maternal origin is assumed also in fibroblasts which along with collagen particles may penetrate into the aspirating needle. From the results ensues that the cells in amniotic fluid are not a homogeneous population of unequivocally foetal origin and that a better technique of collection of samples and cultivation must be developed. PMID- 1873841 TI - [Activation of certain stress axes in spontaneous and surgical deliveries in healthy women and in women with late gestoses]. AB - Within the framework of the stress theory the authors investigated total cortisol levels in the maternal serum during spontaneous delivery and 24 hours after delivery in 20 women half of whom had a non-complicated pregnancy and half had an EPH gestosis. They investigated also cortisol levels in 20 women during delivery by Caesarean section; half of them had a normal pregnancy and half had suffered from gestosis. At the onset of delivery and operation resp. women with gestosis had significantly elevated cortisol levels, as compared with healthy women. During spontaneous delivery the levels of this hormone had a rising trend with the peak during delivery of the foetus and return to pre-delivery values after 24 hours. During Caesarean section the cortisol levels rose only insignificantly and in gestoses they declined already at the end of the operation. In the discussion the authors draw attention to the activation of the stress axes during delivery and attempt to explain the elevated cortisol levels during delivery and in late gestoses. PMID- 1873842 TI - [Problems of epidemiology and diagnosis in the vaginal area. II. Measurement of vaginal pH values and its relation to vaginal diseases]. AB - The authors divided a group of 600 women into 7 sub-groups based on the results of microscopic examination of native preparations, and using indicator papers of MERCK Co. (art. no. 9542) they assessed values of the vaginal pH. The highest values were recorded in a group of women with suppurative bacterial inflammations (mean pH 5.68) and the lowest ones in women with the finding of fungi (mean pH 5.0), cocobacillary flora without leucocytes (mean pII 4.39) and the normal physiological finding of Dorderlein's bacillus (mean pH 4.15). Values higher than 4.8 rule out the possibility of a normal finding in the vagina, lower values, however, do not rule it out entirely. Assessment of pH values in the vagina should be considered part of routine examinations of the vaginal environment. PMID- 1873843 TI - [Screening in pregnant women with a risk of prematurity]. PMID- 1873844 TI - [Leukotrienes as mediators of respiratory tract obstruction in bronchial asthma]. PMID- 1873845 TI - [Models of respiratory tract obstruction]. PMID- 1873846 TI - [Structure and function of dendrites]. PMID- 1873847 TI - [Systemic hemodynamics: the measured pressure and flow determines the percentage of deviation in volume, inotropy and vasoactivity]. PMID- 1873848 TI - Non-01 Vibrio cholerae--Nova Scotia. PMID- 1873849 TI - Rubella surveillance to December 1990--England and Wales. PMID- 1873850 TI - Statement on influenza vaccination for the 1991-1992 season. PMID- 1873851 TI - Cytogenetics of human malignant melanoma. AB - There has been a tremendous recent resurgence of interest in examining chromosomal abnormalities in human cancers (particularly solid tumors). This interest has been stimulated by the molecular examination of recurring chromosome abnormalities, and the recognition that they may pinpoint the location of growth regulatory sequences (e.g. cellular oncogenes). This finding coupled with the clear recognition that specific chromosome abnormalities can also have important diagnostic and prognostic implications, have caused this avenue of research to expand at a significant rate. The following brief review will summarize the current state of knowledge regarding recurring chromosome abnormalities in human malignant melanoma. A discussion of chromosome changes in pre-malignant skin lesions, primary melanoma, and metastatic melanoma is described. Brief descriptions of the potential clinical utility, and biologic relevance of chromosome abnormalities in this disorder are also discussed. PMID- 1873852 TI - Cell adhesion receptor expression during melanoma progression and metastasis. AB - Many steps in melanoma metastasis involve cell-cell or cell-matrix adhesive interactions. The surface molecules which mediate these processes therefore play an important role in regulating melanoma dissemination and their level of expression may alter during the course of tumor progression. Human melanocyte strains and melanoma cell lines have been characterised with regard to levels of cell surface receptors of the integrin family. Increased amounts of at least two integrins, VLA-4 (alpha 4 beta 1) and VnR (alpha v beta 3), appeared to correlate with progression in this tumor, type. A novel VnR composed of an alpha v beta 1 association has been observed in one melanoma cell line and there is the possibility that heterogeneity of integrin composition could affect biological behavior of these tumors. CD44, a cell surface glycoprotein which functions as the major receptor for hyaluronate, is another molecule whose expression increases in transformed cells of the melanocytic lineage. Iterative sorting on the FACS for stable variants, of both human and murine melanomas, expressing low and high levels of CD44 established that lack of expression of this molecule correlated with impaired ability to form pulmonary tumor nodules subsequent to i.v. injection into appropriate recipient mice. These findings illustrate that an understanding of the regulation of melanoma adhesion receptors could provide insights into the process of tumor spread. PMID- 1873854 TI - Antigens of melanocytes and melanoma. AB - Melanoma is a valuable model to study phenotypic traits that are regulated during cell differentiation and malignant transformation. Melanoma cells display extensive phenotypic and antigenic heterogeneity. Studies of this attribute have provided insight into events that take place during normal melanocyte differentiation and give clues to traits that contribute to malignancy. It is possible that the phenotypic and genotypic heterogeneity present among melanoma cells within a single lesion includes a subset of cells with traits that favor tumor progression and metastasis. This review discusses the identification and characterization of antigens expressed by melanoma cells and their potential contribution to melanocyte differentiation and malignant transformation. PMID- 1873853 TI - Growth factors and tyrosine protein kinases in normal and malignant melanocytes. AB - Melanomas are highly variable with respect to aberrant gene expression and chromosomal lesions but share a common characteristic of an acquired independence from environmental growth factors that are needed for proliferation of normal melanocytes. Receptors with tyrosine kinase activity play a critical role in normal melanocyte proliferation and in the uncontrolled growth of melanomas. Normal human melanocytes depend on exogenous peptide growth factors such as basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), or mast cell growth factor (MGF), all of which stimulate receptors with tyrosine kinase activity. In contrast, human melanoma cells from primary nodular and metastatic lesions grow autonomously partially because of inappropriate production of bFGF and continuous activation of the bFGF-receptor kinase. Animal models also provide evidence for the importance of receptor-tyrosine kinases in normal melanocyte proliferation and in malignant transformation. In the mouse, genes residing in three loci in which inactivation mutations lead to piebaldism, the dominant spotting (W), patch (Ph), and Sl encode, respectively, the receptor-kinases c-kit and platelet derived growth factor receptor, and the ligand for c-kit: MGF. In vivo transformation of mouse melanocytes to melanoma, due to constitutive expression of a transmembrane tyrosine kinase, the oncogene ret, was recently demonstrated in transgenic mice. Studies on a fish model, Xiphophorus, in which melanoma is inherited, showed that the dominant tumor inducing gene, Tu, encodes an EGF-receptor related tyrosine kinase which is expressed only in melanomas and not in normal tissues. Taken together, the results suggest that the uncontrolled growth of melanomas is due, in large part, to constitutive activation of receptors with tyrosine kinase activity. PMID- 1873856 TI - Photoimmunology of experimental melanoma. AB - Increases in the incidence of cutaneous melanoma during the past few decades has drawn attention to the possible causes of this cancer. Although sunlight exposure has long been suspected of being a contributing factor, direct evidence of its participation has been difficult to obtain using epidemiological approaches. We have used murine models to investigate the possible contributions of UV radiation to the induction and pathogenesis of melanoma. Our studies demonstrate that UV radiation contributes to the induction of melanoma in a variety of ways, including an indirect, local effect on the skin. Recent evidence suggests that this indirect effect is immunologically mediated. PMID- 1873857 TI - Human cutaneous malignant melanoma as a model for cancer. PMID- 1873855 TI - Human autologous tumor-specific T cells in malignant melanoma. AB - T cell lines and clones with autologous tumor-specific activity have been developed in malignant melanoma by stimulating peripheral blood lymphocytes (PBL), lymph node lymphocytes or tumor-infiltrating lymphocytes (TIL) with autologous melanoma cells in the presence of recombinant interleukin 2 (rIL2). T cell lines and clones have been developed with specific cytotoxicity and/or proliferative responses for autologous melanoma targets but not for allogeneic melanoma tumor cells, autologous normal cells or natural killer (NK)-sensitive targets. The concentration of rIL2 is critical for the generation of autologous tumor-specific T-cell lines, with low rIL2 concentrations (up to 800 IU/ml) facilitating the growth of T-cell lines with tumor-specific activity. The alpha beta T-cell receptor (TCR) and the CD3 antigen are involved in specific cytotoxicity and/or proliferative responses of these T-cell lines and clones. An oligoclonal pattern of beta-chain TCR gene rearrangements was observed on T-cell lines and clones with autologous tumor-specific cytotoxicity, suggesting that they are comprised of T cells that have undergone a clonal expansion in response to particular antigen. Autologous tumor-specific cytotoxic T cells are HLA restricted and recognize on the melanoma tumor cells HLA Class I or possibly Class II antigens plus a tumor-specific determinant. TIL from patients with metastatic melanoma have unique characteristics in comparison with PBL and lymph node lymphocytes and they appear to contain substantial proportions of T cells that have been locally sensitized to autologous tumor cells. Single stimulation of TIL with autologous tumor cells in the presence of rIL2 is sufficient for the generation of T cell lines with autologous tumor-specific activity, whereas, multiple stimulation of PBL and lymph node lymphocytes was required to achieve the same purpose. TIL-derived T cell lines have been expanded in rIL2 in vitro by at least 1,500-fold without losing their activity. Approximately, 40% of the patients exhibited complete or partial responses to adoptive immunotherapy with melanoma TIL and rIL2. PMID- 1873859 TI - Microvascular pressures and resistances in the left ventricular subepicardium and subendocardium. AB - These experiments tested the hypothesis that differences in the distribution of subepicardial and subendocardial microvascular resistances may alter the transmural distributions of microvascular pressures. Isolated blood- and physiological saline-perfused porcine hearts were surgically incised to enable exposure of the subendocardial and subepicardial microcirculations. Microvascular pressures were measured during cardiac arrest and maximal vasodilation at various perfusion pressures to formulate relations between perfusion pressure and microvascular pressure in the different subendocardial (both free wall and papillary muscle) and subepicardial segments. Measurements of arteriolar and venular pressures in both myocardial regions were performed in comparably sized vessels (80-120 microns in diameter). At a coronary perfusion pressure of 100 mm Hg, subendocardial arteriolar and venular pressures were 60 +/- 4 and 33 +/- 3 mm Hg, respectively. In contrast, at the same coronary perfusion pressure, arteriolar and venular pressures in the subepicardial microcirculation averaged 80 +/- 6 and 22 +/- 3 mm Hg, respectively (p less than 0.05 versus subendocardium). At all levels of coronary perfusion pressure, arteriolar pressures were significantly lower in the subendocardium than in the subepicardium (p less than 0.05). Venular pressures were also higher in the subendocardial microcirculation than in the subepicardial microcirculation at all but the lowest perfusion pressure (p less than 0.05). The relative distribution of resistances in arteries, microvessels, and veins was also different between the subepicardium and subendocardium. Specifically, in the subendocardium, arterial and venous resistances were higher, percentage-wise, but microvascular resistance was proportionately lower than that in the subepicardium (p less than 0.05). From these data, it is concluded that the distribution of microvascular resistances and pressures is different during maximal vasodilation in the subepicardial and subendocardial microcirculations of the left ventricle. It is also speculated that differences in autoregulatory capacity and vulnerability to ischemia may be partially related to unequal distribution of microvascular resistances across the wall of the left ventricle. PMID- 1873860 TI - Endothelin 1 enhances myofilament Ca2+ responsiveness in aequorin-loaded ferret myocardium. AB - The influence of endothelin 1 on intracellular Ca2+ transients and isometric contractions was investigated in ferret papillary muscles loaded with the Ca(2+) regulated bioluminescent indicator aequorin. In concentrations of 3 x 10(-9) to 1 x 10(-7) M, endothelin produced dose-dependent increases in the amplitudes of both aequorin light signals (maximum, 31 +/- 12%) and developed tension (maximum, 64 +/- 13%). The peak aequorin light [( Ca2+]i)-peak tension curve generated by increasing endothelin concentrations was steeper and shifted to the left of the curve generated by varying [Ca2+]o; however, the maximum developed tension produced by endothelin did not exceed that produced by 6 mM [Ca2+]o. The effect of endothelin on the amplitude of the aequorin light signal was less than the effect of [Ca2+]o for similar levels of tension development. Moreover, 1 x 10(-7) M endothelin caused an upward shift in the peak aequorin light-peak tension curve generated by varying [Ca2+]o and increased the maximum twitch force by about 12%. The contractions were prolonged, whereas the time course of the Ca2+ transient was not changed in the presence of endothelin. When the function of the sarcoplasmic reticulum was inhibited by 6 microM ryanodine, 10(-7) M endothelin still increased the force generation without increasing the intracellular peak Ca2+, either during isometric twitches or during tetani.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873858 TI - Growth factors in melanoma. AB - Human melanoma cells in culture are the source of a wide variety of polypeptide growth factors. Melanoma-derived basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF)-A and PDGF-B chains, transforming growth factor (TGF)-alpha and TGF-beta, interleukin (IL)-1 alpha and IL-1 beta, and melanoma growth stimulatory activity (MGSA) have similar biochemical and functional properties when compared to their counterparts produced by untransformed cells. In contrast to melanoma cells, normal melanocytes, even under optimal growth conditions, express only TGF-beta 1 and MGSA at detectable levels suggesting that production of the other growth factors is a tumor-associated phenomenon. Recent evidence suggests that at least two of the growth factors, bFGF and MGSA, contribute to autocrine growth stimulation of melanoma cells. Whether PDGF, TGF alpha, IL-1, and TGF-beta act in an autocrine mode is unclear at present. However, these four growth factors are among those secreted by melanoma cells and, therefore, can be expected to interact with normal cells of the tumor stroma in vivo. Such paracrine effects include not only growth modulation in the context of angiogenesis and stroma formation, but also tissue degradation by proteolytic enzymes, the modification of extracellular matrix composition, and expression of adhesion receptors. PMID- 1873861 TI - Alterations in myocyte shape and basement membrane attachment with tachycardia induced heart failure. AB - Chronic supraventricular tachycardia (SVT) results in left ventricular (LV) dilatation and dysfunction. However, the underlying mechanisms responsible for LV failure in this setting are not known. LV force production is dependent on the coupling of myocytes to the extracellular matrix, which is mediated through the basement membrane. This study was designed to determine whether alterations in myocyte geometry and basement membrane attachment are associated with LV failure in a pacing-induced model of cardiomyopathy. Echocardiographic measurement of LV function was performed in six pigs after 3 weeks of pacing-induced SVT (240 beats/min) and in eight sham-operated controls. Myocytes from these hearts were isolated, and attachment studies to specific components of the basement membrane were performed using laminin, fibronectin, and collagen IV. The SVT group when compared with the control group showed a significant reduction of LV fractional shortening (14 +/- 2% versus 31 +/- 2%, respectively; p less than 0.05), increased end-diastolic dimension (50 +/- 1 versus 35 +/- 1 mm, respectively; p less than 0.05), and lengthening of isolated myocytes (196 +/- 18 versus 142 +/- 9 microns, respectively; p less than 0.05). Myocyte attachment to laminin (50 micrograms/ml) was significantly decreased at 60 minutes in the SVT group compared with the control group (18.2 +/- 4.5 versus 60.9 +/- 4.5 cells/mm2, respectively; p less than 0.05). Similar reductions in myocyte attachment to fibronectin and collagen IV were observed. Ultrastructural examination of LV sections revealed focal disruptions of the basement membrane-sarcolemmal interface and a reduced number of sarcolemmal festoons in SVT hearts compared with control hearts (0.8 +/- 0.6 versus 2.8 +/- 0.8/4 microns, respectively; p less than 0.05). These alterations in myocyte morphology and basement membrane attachment may contribute to the LV failure associated with chronic SVT. Further, these structural changes may play a significant role in the progression of ventricular dysfunction as well as recovery from chronic SVT. PMID- 1873862 TI - Vasoconstriction of canine coronary collateral vessels with vasopressin limits blood flow to collateral-dependent myocardium during exercise. AB - This study was performed to test the hypothesis that active constriction of coronary collateral vessels can worsen hypoperfusion of collateral-dependent myocardium during exercise. Studies were performed in seven adult mongrel dogs in which intermittent followed by permanent occlusion of the left circumflex coronary artery produced an area of collateral-dependent myocardium without gross evidence of infarct. Myocardial blood flow was determined with microspheres while measurement of aortic and distal coronary pressures allowed calculation of collateral and small vessel resistance at rest and during treadmill exercise. The ability of collateral vessel constriction to limit blood flow was assessed by infusion of vasopressin during exercise. During control conditions, blood flow in the collateral zone underwent a subnormal increase during exercise in comparison with the normal zone (1.74 +/- 0.27 versus 2.50 +/- 0.40 ml/min/g, respectively, p less than 0.05). Infusion of vasopressin in a dose that caused no change in normal zone flow (0.01 microgram/kg/min i.v.) produced a 30 +/- 5% further decrease in flow to the collateral zone (p less than 0.01). This decrease in collateral zone flow resulted from a 48 +/- 14% increase in transcollateral resistance in response to vasopressin infusion (p less than 0.01), as well as a 40 +/- 9% increase in small vessel resistance in the collateral zone (p less than 0.01). These data demonstrate that active constriction of both collateral vessels and coronary resistance vessels can contribute to hypoperfusion of collateral dependent myocardium during exercise. PMID- 1873863 TI - Functional development of the creatine kinase system in perinatal rabbit heart. AB - The functional development of the creatine kinase system has been studied in rabbit heart during perinatal growth. Fiber bundles were obtained from left ventricles of fetal rabbits at the 30th day of gestation, newborn rabbits aged 1, 3, 8, and 17 days, and adult rabbits. Total creatine kinase activity was constant during perinatal development, whereas myofibrillar bound creatine kinase activity increased 15-fold during the first postnatal week. Functional activity of myofibrillar creatine kinase was assayed in Triton X-100-skinned fibers by its ability to induce active tension in the absence of ATP or to relax rigor tension. It was very low in 1-day-old newborns and increased during the first 2 weeks to reach adult levels 17 days after birth. Functional activity of mitochondrial creatine kinase was determined in saponin-skinned fibers. Creatine-stimulated respiration appeared only after birth and increased gradually between 1 and 17 days after birth. The results show that, although the two creatine kinase isoforms (mitochondrial and myofibrillar) are expressed at different stages during development, their functional activities appear in parallel in mitochondria and myofibrils. Early postnatal development is characterized by binding of creatine kinase isoenzymes to intracellular organelles. Such compartmentation participates in the postnatal cardiac cellular maturation. PMID- 1873864 TI - Flow-mediated dilatation of the basilar artery in vivo. AB - Flow-mediated dilatation has been described mainly in peripheral conduit arteries. The goal of this study was to examine mechanisms and functional implications of flow-mediated dilatation in large cerebral arteries in vivo. Vessel diameter and velocity of blood flow through the basilar artery were measured using a cranial window in 45 anesthetized rats. Mean blood flow velocity through the basilar artery increased by 94 +/- 8% during unilateral common carotid artery occlusion and 203 +/- 13% during bilateral occlusion. Diameter of the basilar artery increased by 10 +/- 1% during unilateral common carotid artery occlusion and 29 +/- 2% during bilateral occlusion from control diameter of 275 +/- 8 microns. Vasodilatation appeared with a delay of 13 +/- 1 seconds after the onset of the increase in flow velocity. With systemic arterial pressure maintained at baseline levels, pressure in the basilar artery (servonull) decreased initially during carotid occlusion, and during dilatation of the basilar artery, pressure was restored partially toward normal. Indomethacin (10 mg/kg i.v.), topical application of tetrodotoxin (10(-6) M), NG-monomethyl L arginine (5 x 10(-6) M), tetraethylammonium chloride (10(-2) M), glibenclamide (10(-5) M), SKF 525A (3 x 10(-5) M), and ouabain (10(-5) M) had no effect on flow mediated dilatation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873865 TI - Acetylcholine-induced coronary vasoconstriction and vasodilation in tranquilized baboons. AB - To determine the effects of acetylcholine on the coronary bed in the baboon and whether the effects preceded or followed the action of acetylcholine on ventricular function, eight adult baboons (Papio anubis) were instrumented to measure left ventricular (LV) and mean arterial pressures, LV dP/dt, regional myocardial function, and coronary blood flow. Acetylcholine was injected locally through a catheter positioned in the coronary artery ostium using fluoroscopic guidance in intact sedated baboons. With heart rate held constant, intracoronary acetylcholine (0.5 micrograms/kg) reduced coronary blood flow by 82 +/- 4% from a baseline value of 34 +/- 4 ml/min without a significant change in mean arterial pressure and with a reduction in LV dP/dt of only 12 +/- 3%. The decrease in coronary blood flow occurred before either LV dP/dt or regional myocardial function fell in the region of the heart receiving acetylcholine. After the intense coronary constriction, a later phase characterized by dilation was observed. The changes in coronary blood flow with acetylcholine were unaffected by combined alpha- and beta-adrenoceptor blockades but were abolished by muscarinic blockade. Low doses of acetylcholine elicited only coronary vasodilation. All doses of acetylcholine, administered directly into the iliac artery, also elicited only iliac vasodilation. Intracoronary acetylcholine in conscious dogs also induced only coronary vasodilation, whereas in conscious calves at higher doses, initial vasoconstrictor responses were observed, which also preceded reductions in regional myocardial function. These results suggest that the controversy surrounding the effects of acetylcholine can be reconciled on the basis of species, vascular bed studied, and dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873866 TI - Combined effect of neonatal sympathectomy and adrenal demedullation on blood pressure and vascular changes in spontaneously hypertensive rats. AB - Neonatal sympathectomy using a combined treatment with antiserum to nerve growth factor and guanethidine during the first 4 weeks after birth was carried out in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Bilateral adrenal demedullation was performed in 4-week-old sympathectomized SHR and WKY rats. The development of hypertension in SHR was prevented by sympathectomy, but the blood pressure (BP) was still higher than in age-matched WKY rats. Demedullation reduced the BP of sympathectomized SHR to the same level as that of WKY rats. Heart rates of SHR and WKY rats were not affected by the treatments. Morphometric measurements of the mesenteric arteries showed that sympathectomy significantly reduced the medial mass in the mesenteric arteries of SHR, mainly through a reduction in the number of smooth muscle cell layers. In sympathectomized SHR, demedullation increased the lumen size of muscular arteries under maximally relaxed conditions, which might explain the further reduction in BP in these animals. Demedullation in sympathectomized SHR and WKY rats caused a decrease in smooth muscle cell layers in the superior mesenteric artery, but the same treatment resulted in a slight increase in the number of smooth muscle cell layers in the large and small mesenteric arteries of SHR and WKY rats. Adventitial area was increased in some mesenteric arteries of SHR and WKY rats by sympathectomy, and demedullation caused a further increase in the size of adventitia in WKY rats. Heart weight in SHR was normalized to the level found in WKY rats by sympathectomy and demedullation. We conclude that in sympathectomized SHR, the elevated BP was maintained by the adrenal medulla. PMID- 1873867 TI - Influence of electrical axis of stimulation on excitation of cardiac muscle cells. AB - Orthogonal sequential shock can defibrillate the heart with greater efficacy compared with single shock defibrillation. In this study we tested the hypothesis that cardiac cells have a preferred orientation in their response to excitatory extracellular electric fields, so that orthogonal shocks may stimulate distinct populations of cells. A micropaddle electrode system was used to deliver rectangular pulses for extracellular field stimulation of individual heart cells. We found that single frog and guinea pig ventricular myocytes are excitable with rectangular pulse field stimulation over a wide range of pulse durations, ranging from 10 msec to as little as 20 microseconds. The excitation field strength varies inversely with pulse duration as described by the Weiss-Lapicque equation, although the frog myocytes show a significant "notch" at pulse durations of approximately 1-2 msec, and the guinea pig myocytes are more excitable than predicted for pulse durations of less than 0.2 msec. Every myocyte tested was more excitable when the long axis of the cell was oriented parallel to the stimulating field than when perpendicular to the field. For 2-msec pulses, the difference in field strength was a factor of 5.8 +/- 2.0 (n = 30) for frog and 2.6 +/- 0.5 (n = 23) for guinea pig myocytes. Complete excitation strength duration curves were obtained in seven frog and 14 guinea pig cells for both parallel and perpendicular cell orientations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873868 TI - Postischemic myocardial "stunning". Identification of major differences between the open-chest and the conscious dog and evaluation of the oxygen radical hypothesis in the conscious dog. AB - Recent studies suggest that oxygen-derived free radicals contribute to the pathogenesis of postischemic myocardial dysfunction (myocardial "stunning"). This concept, however, is predicated exclusively on results obtained in open-chest preparations, which are subject to the confounding influence of many unphysiological conditions. The lack of supporting evidence in more physiological animal models represents a major persisting limitation of the oxy-radical hypothesis of myocardial stunning. The goal of this study was to address two fundamental (and related) questions: 1) Does the open-chest animal model alter the phenomenon of myocardial stunning? 2) If so, how valid are the concepts, derived from such a model, regarding the pathogenetic role of oxy-radicals? In part 1 of the study, myocardial stunning after a 15-minute coronary occlusion was compared in 30 pentobarbital-anesthetized open-chest dogs and in 19 conscious dogs. For any given level of collateral flow during occlusion, the recovery of systolic wall thickening after reperfusion was markedly less in open-chest animals. In an additional group of five open-chest dogs, a close inverse relation was noted between body temperature and postischemic wall thickening, indicating that the recovery of the stunned myocardium in acute experiments may vary markedly depending on how temperature is controlled. Because of these major differences between open-chest and conscious dogs, the oxy-radical hypothesis needs to be tested in the latter model. Thus, in part 2 of the study, conscious unsedated dogs undergoing a 15-minute coronary occlusion were randomized to an intravenous infusion of either saline (19 coronary occlusions) or superoxide dismutase (SOD) plus catalase (CAT) (21 coronary occlusions). Despite the fact that the plasma levels of SOD and CAT declined rapidly after reperfusion, postischemic wall thickening was significantly greater in treated compared with control dogs throughout the first 6 hours of reflow. Thus, a brief (60-minute) infusion of SOD and CAT produced a sustained improvement of recovery of contractility. The magnitude of this beneficial effect was a function of the severity of ischemia: the lower the collateral perfusion, the greater the improvement effected by the enzymes. The accelerated recovery produced by SOD and CAT was not followed by any deterioration of contractility, suggesting that postischemic dysfunction is not a teleologically "protective" phenomenon. In conclusion, the severity of myocardial stunning is greatly exaggerated by the unphysiological conditions present in the barbiturate-anesthetized open-chest dog.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1873869 TI - Rabbit ear model of injury-induced arterial smooth muscle cell proliferation. Kinetics, reproducibility, and implications. AB - Recently, considerable interest has focused on the vascular smooth muscle cell (SMC) response to injury, particularly as it relates to restenosis after angioplasty. In an effort to find an optimal experimental model of arterial SMC proliferation after injury, we examined the effects of external injury to the central artery of the rabbit ear and assessed the reproducibility, morphological changes, and time course of cellular proliferation after such an injury. With rabbits under general anesthesia, direct pressure was applied at two sites along the central artery of the ears of 19 New Zealand White rabbits. Rabbits were maintained on a diet of 2.4% fat and 0.001% cholesterol throughout the experiment. In seven rabbits examined after 21 days, marked SMC proliferation with neointimal formation was observed at all 28 sites (100%). Mean neointimal area, expressed as a percentage of the area of the tunica media, was 82 +/- 40% (range, 21-203%). Compared with the uninvolved artery displaced 2 mm from the injury site, mechanical crush caused a 38% increase in total vessel area (p less than 0.001), a 40% decrease in luminal area (p less than 0.002), and no change in the area of the media. Serial histological studies were performed 1-42 days after injury, using light and electron microscopy and bromodeoxyuridine immunohistochemistry. Beginning at day 3, activated medial SMCs were noted to migrate through defects in the internal elastic membrane, with a gradual increase in neointimal area between days 5 and 12. Peak DNA synthesis was identified in the media 5 days after injury, with proliferative activity shifting almost exclusively to the neointima thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873870 TI - Mechanism of the enhanced epidermal growth factor-induced growth response of genetically hypertensive vascular myocytes. AB - Although enhanced growth of the vascular myocyte is believed to play a role in hypertensive cardiovascular disease, the cellular basis of altered growth regulation is not completely understood. The present study demonstrates that in the presence of 10% fetal calf serum, the logarithmic growth rate of cultured mesenteric artery myocytes of the spontaneously hypertensive rat (SHR) is similar to that of the normotensive Wistar-Kyoto (WKY) control rat. However, in the presence of low levels of fetal calf serum, SHR myocytes respond to epidermal growth factor (EGF) with increased growth, whereas WKY cells do not. This difference does not result from different numbers or affinities of EGF receptors in these cell lines. Examination of EGF-induced growth responses of SHR and WKY myocytes in the presence of varying levels of insulin or fetal calf serum indicates that, compared with WKY myocytes, SHR myocytes have a lower requirement for factors that confer competence to respond to EGF. Another property of the SHR myocytes is an elevation of free intracellular Ca2+. To determine whether a difference in cellular Ca2+ metabolism might play a role in the differential growth response, growth of myocytes in medium containing 0.25, 0.75, or 1.25 mM extracellular Ca2+ and 5% fetal calf serum was examined. Myocytes of SHR showed enhanced growth in the presence of 5% fetal calf serum at all levels of extracellular Ca2+. It is concluded that, although vascular myocytes of SHR and WKY rats have the capacity to grow at similar rates, under limiting conditions, the SHR myocyte growth response is enhanced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873871 TI - Diastolic anisotropic properties of the left ventricle in the conscious dog. AB - The role of myocardial anisotropy in determining change in left ventricular shape during diastolic filling has not yet been demonstrated. Therefore, 11 conscious dogs were instrumented with global ultrasonic dimension transducers to measure left ventricular major and minor axis diameters and equatorial wall thickness. Myocardial geometry was represented as a three-dimensional ellipsoidal shell. Left ventricular transmural pressure was measured with micromanometers, and ventricular volume was varied by inflation of vena caval occluders. Left ventricular wall strains and stresses calculated from the ellipsoidal shell model agreed closely with those measured directly by myocardial force and dimension transducers. Unequal normalized diastolic stress-strain relations were observed in the latitudinal, longitudinal, and wall thickness directions, reflecting anisotropic mechanical properties of the myocardium. Although a greater wall stress in the latitudinal versus longitudinal axis was predicted adequately from left ventricular geometry alone, the observed latitudinal strain exceeded longitudinal strain by an amount greater than was predicted by geometric considerations alone, suggesting that myocardial anisotropy contributes significantly to changes in ventricular shape during diastolic filling. PMID- 1873872 TI - Distribution of carbon flux within fatty acid utilization during myocardial ischemia and reperfusion. AB - Twenty-nine intact, working pig hearts were extracorporeally perfused and divided into two study groups (16 Aerobic and 13 Ischemic/Reflow hearts). Step function, equilibrium labeling with [14C]palmitate was used to develop uptake and washout curves of radioactive fatty acid products contained in coronary effluent during either aerobic perfusion or reperfusion after ischemia (60% reduction in left anterior descending coronary flow for 30 minutes). Left anterior descending control flows were slightly overperfused in Aerobic hearts (18% higher than in Ischemic/Reflow hearts); otherwise, circumflex and right coronary flows, left ventricular pressure, and serum fatty acids and blood sugar levels were comparable between groups. As expected in Ischemic/Reflow hearts, recovery of regional systolic shortening and myocardial oxygen consumption in reperfusion was only modestly impaired (-20% and -19%, respectively, not significant and p less than 0.011 compared with preischemic values, not significant from Aerobic hearts). The only significant metabolized product to be released from labeled fatty acid utilization in either group was 14CO2. A smaller fatty acid pool also was measured and accounted for by that contained in the coronary intravascular volume. We could determine no significant back diffusion of fatty acids from myocardium in either perfusion condition. Uptake time constants of the early phase of 14CO2 production also were virtually identical in both groups (19.9 +/- 3.2 versus 16.7 +/- 3.2 minutes in Aerobic and Ischemic/Reflow hearts, respectively) and strongly correlated with hemodynamics as described by heart rate. In washout studies, tissue radioactivity in the aqueous soluble and fatty acid pools declined in both study groups, and counts in complex lipids and cholesterol/cholesteryl esters remained steady, whereas those in triacylglycerols varied. Washout of 14CO2 in both groups never reached background radioactivity over a 40-minute sampling after cessation of isotope infusion into the perfusate, suggesting slow release of trapped substrate from intracellular pools, which then proceeded to fatty acid oxidation. In conclusion, these experiments have demonstrated very similar findings with respect to fatty acid uptake, storage, and release characteristics between aerobic and reperfused myocardium. We found no differences in preferred substrate utilization and oxidation as a result of reversible ischemia followed by reflow. PMID- 1873873 TI - Myocardial glucose utilization. Failure of adenosine to alter it and inhibition by the adenosine analogue N6-(L-2-phenylisopropyl)adenosine. AB - The effects of adenosine and the nonmetabolizable adenosine analogue N6-(L-2 phenylisopropyl)adenosine (PIA) on glucose transport or metabolism were determined in purified myocardial sarcolemmal vesicles, isolated cardiocytes, and perfused hearts. Adenosine (100 microM) did not affect hexose transport in myocytes. Also, adenosine deaminase, added to metabolize adenosine to inosine, did not alter transport of hexose into myocytes regardless of whether or not insulin was present. In contrast, PIA effectively inhibited 3-O-methyl-D-glucose uptake in myocytes even during insulin stimulation. PIA inhibited D-glucose specific transport in both rat and bovine cardiac sarcolemmal vesicles (Ki = 26 microM at [D-glucose] = 5 mM). However, insulin did not affect glucose transport in sarcolemmal vesicles, which implies that receptor-coupled processes probably are not intact in this preparation. Thus, inhibition of PIA may not be receptor mediated. Also, PIA inhibited binding of cytochalasin B to bovine cardiac sarcolemmal vesicles, which supports the idea that PIA inhibits glucose flux by binding to the glucose transporter. To determine if adenosine altered glucose metabolism rather than transport, we measured the rate of 3H2O production from metabolism of D-[2-3H]glucose in paced rat hearts ([D-glucose] = 5.5 mM, [pyruvate] = 0.2 mM) perfused with a range of PIA or adenosine concentrations with or without 0.01 microM insulin. Adenosine (0.01-100 microM) in the presence or absence of insulin increased coronary flow but did not change glycolytic rates. Similar results were obtained with PIA (no insulin) rather than adenosine in the perfusate. However, with glucose as the only exogenous substrate, 100 microM PIA inhibited glycolysis by approximately 50%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873874 TI - Intracellular calcium transients and arrhythmia in isolated heart cells. AB - Intracellular calcium ([Ca2+]i) elevation may mediate cardiac arrhythmias. However, direct measurement of the rapid alterations of [Ca2+]i on a beat-to-beat basis using fast temporal resolution and without signal averaging in the spontaneously beating in vivo heart is lacking. Furthermore, data from an isolated spontaneously beating myocyte preparation that develops arrhythmia similar to that in the in vivo heart are unavailable. We measured rapid changes of [Ca2+]i with fast temporal resolution in isolated spontaneously beating neonatal rat ventricular myocytes with cell-to-cell communication and characterized the interrelation between [Ca2+]i and arrhythmia. An elevated extracellular calcium ([Ca2+]o) concentration of 10.8 mM induced premature beats, a rapid beating rate (tachyarrhythmia), and chaotic or fibrillatory beating activity in a small group of myocytes. [Ca2+]i levels during systole increased from the nanomolar to micromolar concentration range before arrhythmia development. Spontaneous oscillations of [Ca2+]i during diastole could evoke a spontaneous tachyarrhythmia. In the presence of [Ca2+]i elevation, a spontaneous tachyarrhythmia could induce severe [Ca2+]i overload. Reduction of [Ca2+]i with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid AM (5 microM) in the presence of 10.8 mM [Ca2+]o reversed the arrhythmia. In single ventricular myocytes superfused with 10.8 mM [Ca2+]o, oscillations of membrane potential characteristic of transient inward current occurred that were prevented by ryanodine (0.1 microM), an inhibitor of Ca2+ flux across the sarcoplasmic reticulum. This study characterizes 1) an isolated multicellular myocyte model of arrhythmia similar to that evident in in vivo hearts, 2) elevation of [Ca2+]i with systolic [Ca2+]i levels of 1-3 microM and diastolic [Ca2+]i oscillations before the initiation of arrhythmia, 3) tachyarrhythmia as a cause of severe [Ca2+]i overload, which may be important in the perpetuation and degeneration of arrhythmias, and 4) reversal of arrhythmia with reduction of [Ca2+]i. The results in the isolated myocyte model may have relevance to the generation and perpetuation of certain cardiac arrhythmias associated with calcium overload. PMID- 1873875 TI - Dose-dependent inhibition of stretch-induced arrhythmias by gadolinium in isolated canine ventricles. Evidence for a unique mode of antiarrhythmic action. AB - Transient diastolic dilatation of the isolated canine left ventricle predictably elicits arrhythmias. To test the hypothesis that such arrhythmias may be mediated by sarcolemmal stretch-activated channels, we attempted to inhibit stretch induced arrhythmias with gadolinium (Gd3+), a potent stretch-activated channel blocker. In experiments with six isolated canine hearts, left ventricular volume was increased for 50 msec during early diastole and then returned to initial volume by a computerized servopump. The stretch volume was adjusted to yield a probability of eliciting a stretch-induced arrhythmia of 95 +/- 2% before treatment with Gd3+. When Gd3+ (1-10 microM) was administered, dose-dependent suppression of stretch-induced arrhythmias was observed. The probability of a stretch-induced arrhythmia was reduced to 13 +/- 10% (p less than 0.05) with 10 microM Gd3+. Washout of Gd3+ completely reversed this effect. Since Gd3+ is known to be a calcium channel antagonist, we compared the effect of Gd3+ on stretch induced arrhythmias with that of verapamil and nifedipine. These calcium channel blockers produced no demonstrable inhibition of stretch-induced arrhythmias when administered at concentrations (1 microM) that substantially depressed left ventricular pressure development. Thus, our results indirectly implicate stretch activated channels in the genesis of stretch-induced arrhythmias and provide preliminary evidence for a potential new mode of antiarrhythmic drug action- blockade of stretch-activated channels. PMID- 1873876 TI - Platelets stimulate expression of endothelin mRNA and endothelin biosynthesis in cultured endothelial cells. AB - Modulation of the biosynthesis of the vasoconstrictor peptide endothelin was studied in cultured endothelial cells. Immunoreactive endothelin (irET) levels were significantly elevated in conditioned medium from bovine pulmonary artery endothelial (BPAE) or human umbilical vein endothelial cells when coincubated with washed human platelets. Platelets (approximately 200,000 cells/microliters) enhanced irET levels approximately 250% over basal levels. Stimulation of irET levels in BPAE cell-conditioned medium by platelets was time and platelet number dependent. Platelets, as well as thrombin and transforming growth factor-beta 1, stimulated the expression of preproendothelin-1 mRNA in a time-dependent manner. Coincubation of low doses of thrombin (0.1 unit/ml) and subthreshold concentrations of platelets with BPAE cells resulted in a further enhancement of irET levels in conditioned medium. Platelet-mediated stimulation of irET production was not significantly affected by indomethacin (1 microM) or the platelet-activating factor receptor antagonist WEB 2086 (1 microM); however, coincubation of endotoxin (100 ng/ml) with platelets and BPAE cells resulted in significantly higher levels of irET. Whether direct contact or adhesion between platelets and endothelial cells is necessary for stimulating irET release was studied by separating platelets from BPAE cells with a 0.4 microns permeable membrane. Under these conditions, platelets still produced significant elevations (approximately 190% over basal levels) in irET levels in BPAE cell-conditioned medium. In addition, platelet-free buffer from agonist-induced platelet aggregation also significantly enhanced irET production (200% over basal values). These data indicate that a platelet-derived regulatory factor can induce the biosynthesis of endothelin from cultured endothelial cells and also suggest that platelets might play a role in vasomotor regulation via a novel intercellular interaction with the endothelium. PMID- 1873877 TI - Optical recordings in the rabbit heart show that defibrillation strength shocks prolong the duration of depolarization and the refractory period. AB - The present data were obtained using the technique of optical recording with the voltage-sensitive dye WW781. This technique, unlike electrical methods, was able to provide uninterrupted recordings free of artifacts during defibrillation shocks. Optical recordings were made from sites on the ventricular epicardium of perfused rabbit hearts during electrical pacing. Continuous recordings of the electrophysiological responses of an intact heart to defibrillation threshold strength shocks were made. It was shown that these shocks were able to stimulate normal-appearing action potentials in nonrefractory myocardium. A new and unexpected finding was that defibrillation threshold-strength shocks were also able to evoke a sustained, depolarizing response from myocardium already undergoing an action potential. This prolonged the time that the myocardium remained in the depolarized state. Prolongation of the depolarized state was accompanied by an equal prolongation of the refractory period. There was no indication that this depolarizing shock response was due to damage of the myocardium by the shock, to heterogeneous electrical responses in the optical recording area, or to the methods used in this study. It is hypothesized that these shocks were able to elicit a new action potential in already depolarized myocardium by hyperpolarizing portions of the myocardium's cellular membranes and, in so doing, to reactivate the fast sodium current. This effect, if prevalent in a fibrillating ventricle, could play a role in the defribillation process by effectively resynchronizing electrical activity. PMID- 1873878 TI - Fatty acid uptake in normal human myocardium. AB - Fatty acid binding protein has been found in rat aortic endothelial cell membrane. It has been identified to be a 40-kDa protein that corresponds to a 40 kDa fatty acid binding protein with high affinity for a variety of long chain fatty acids isolated from rat heart myocytes. It is proposed that this endothelial membrane fatty acid binding protein might mediate the myocardial uptake of fatty acids. For evaluation of this hypothesis in vivo, influx kinetics of tracer-labeled fatty acids was examined in 15 normal subjects by scintigraphic techniques. Variation of the plasma fatty acid concentration and plasma perfusion rate has been achieved by modulation of nutrition state and exercise conditions. The clinical results suggest that the myocardial fatty acid influx rate is saturable by increasing fatty acid plasma concentration as well as by increasing plasma flow. For analysis of these data, functional relations describing fatty acid transport from plasma into myocardial tissue in the presence and absence of an "unstirred layer" were developed. The fitting of these relations to experimental data indicate that the free fatty acid influx into myocardial tissue reveals the criteria of a reaction on a capillary surface in the vicinity of flowing plasma but not of a reaction in extravascular space or in an unstirred layer and that the fatty acid influx into normal myocardium is a saturable process that is characterized by the quantity corresponding to the Michaelis Menten constant, Km, and the maximal velocity, Vmax, 0.24 +/- 0.024 mumol/g and 0.37 +/- 0.013 mumol/g(g.min), respectively. These data are compatible with a nondiffusional uptake process mediated by the initial interaction of fatty acids with the 40-kDa membrane fatty acid binding protein of cardiac endothelial cells. PMID- 1873879 TI - Mechanisms of contraction induced by human leukocytes in normal and atherosclerotic arteries. AB - Activation of leukocytes results in the release of a variety of vasoactive substances that may modulate vascular tone. We studied the effect of human polymorphonuclear (PMN) and mononuclear (MONO) leukocytes on quiescent femoral arteries in vitro. Arteries were obtained from normal and atherosclerotic cynomolgus monkeys. In normal arteries, stimulation of PMNs (3 and 5 x 10(6) cells/ml) with either thrombin (5 units/ml) or complement C5a (0.5 micrograms/ml) resulted in endothelium-independent contraction (approximately 25% of maximum contraction with 80 mM KCl). Vasocontraction was augmented in the presence of superoxide dismutase (150 units/ml) and was significantly impaired in the presence of the hydroxyl radical scavengers mannitol (20 mM) and deferoxamine (1 mM). Catalase (1,200 units/ml) or L-alanine (20 mM) did not modify this effect of PMNs. In contrast to PMNs, vasocontraction in response to MONOs was not altered by the addition of radical scavengers. Pretreatment of PMNs and MONOs with indomethacin (10 microM) or nordihydroguaiaretic acid (20 microM) did not influence vascular responses. Supernatant of thrombin-stimulated PMNs and MONOs also produced vasocontraction (approximately two thirds of the effect of intact cells). This vasocontractor factor (or factors) was heat stable (30 minutes, 95 degrees C) and had a molecular weight less than 1,000 as determined by ultrafiltration. Stimulation of MONOs or PMNs (3 and 5 x 10(6) cells/ml) produced a similar response in normal arteries. In contrast, the constrictor response in atherosclerotic arteries to MONOs (5 x 10(6) cells/ml) was significantly greater than to PMNs. We conclude that stimulated human PMNs and MONOs contract arteries in vitro by release of at least two factors. One factor appears to be heat stable, with a molecular weight less than 1,000. The vascular response to PMNs, but not to MONOs, appears to involve the generation of hydroxyl radicals. The response to MONOs is greater than the response to PMNs in atherosclerotic, but not in normal, arteries. PMID- 1873880 TI - Copper loading of hearts increases postischemic reperfusion injury. AB - We studied the role of copper as a potential mediator of postischemic reperfusion injury in the isolated, perfused rat heart. Hearts were equilibrated with Krebs Henseleit buffer for 10 minutes and then loaded with copper by way of perfusion with buffer containing 20 microM copper(II)-bis-histidial for 30 minutes. Control hearts were perfused with Krebs-Henseleit buffer alone during the loading period. Hearts than were washed with buffer for 10 minutes and subjected to 20 minutes of normothermic global ischemia followed by 30 minutes of reperfusion. Atomic absorption spectroscopy revealed a 67% increase in total copper content in loaded hearts by the end of the wash. By the end of the 30-minute period of reperfusion, control hearts demonstrated a 50-60% recovery of myocardial function as determined by peak systolic pressure, contractility, and heart rate. In contrast, copper-loaded hearts exhibited virtually no functional recovery within the 30 minute time period. Using salicylate as a probe, we determined that peak and duration of .OH formation appears to be increased in copper-loaded hearts during reperfusion. Furthermore, efflux of lactic dehydrogenase was significantly increased in copper-loaded hearts. Our results clearly demonstrate that increasing cardiac content of copper results in enhanced postischemic reperfusion injury associated with increased formation of .OH, thus suggesting an important catalytic role for this transition metal. PMID- 1873881 TI - [Activation of the latent Toxoplasma infection and cyst formation in mice]. AB - Latent Toxoplasma infection in mice inoculated with the low virulent Beverley strain (BEV) and avirulent Fukaya strain (FUK) was reactivated by prednisolone administration. Parasitaemia reappeared and the organism could be continuously isolated from the lymph nodes by mouse passage. No distinct decrease in specific antibody levels was observed when the sera were assayed by dye test and latex agglutination test. A significant increase in the number of brain cysts in infected mice was noted at the third week of infection while the challenge infection and steroid immunosuppression treatment resulted in an enhancement of cyst formation. A hypothesis was, therefore, proposed that the cyst formation in tissues might be regulated by the immune response of infected host to Toxoplasma infection. PMID- 1873882 TI - [Observations on the development of quantitatively inoculated Brugia malayi microfilariae in Anopheles sinensis and Culex quinquefasciatus]. AB - With an improved technique, quantitative inoculation of Brugia malayi microfilariae (mff) into Anopheles sinensis and Culex quinquefasciatus was carried out in our laboratory in 1988. The development of B. malayi mff in these two species of mosquitoes was observed. In the system of B. malayi and An. sinensis, a well-fitted linear correlation appeared between the number of mff inoculated and the infective larva (L3) positive rate (r = 0.9910; P less than 0.01). The regression equation with the regression coefficient of 8.490 suggested a high susceptibility of this species of mosquito to B. malayi even under the condition of experimental inoculation. The quantitative relationship between the number of mff inoculated and the average filarial maturity rate was also exhibited. At the same dosages of 4 and 10 mff/mosquito, the L3 positive rates and the average filarial maturity rates in An. sinensis were much higher than those in Cx. quinquefasciatus (P less than 0.01), indicating significant difference occurred inside the bodies of these two species of mosquitoes. PMID- 1873883 TI - [Electron microscopic cytochemistry studies on membrane-bound organelles of Trichomonas hominis]. AB - This paper presents the results of an electron microscopy cytochemistry study on the membrane-bound organelles of Trichomonas hominis. Acid phosphatase (ACP) and cytidine monophosphatase (CMPase) were located in the primary lysosomes, digestive vacuoles, as well as in the parabasal body stacks, being usually in its mature surface sacs. Thiamine pyrophosphatase (TPPase) and nicotinamide adenine dinucleotide phosphatase (NADPase) were found in the saccules, being on the mature surface and in the intermediate saccules of parabasal body stacks, respectively. The reactive products of peroxidase (POase) were seen only in the digestive vacuoles. Cytochrome oxidase (COase) and catalase (Cat) reactions were both negative. It is suggested that T. hominis lacks mitochondrion and microbody but possesses hydrogenosome. The parabasal body, endoplasmic reticulum and hydrogenosome were stained well with the U-Pb-Cu impregnation technique. PMID- 1873884 TI - [Determination of circulating antigen in cysticercosis patients using McAb-based ELISA]. AB - For the first time, the determination of circulating antigen in patients with cysticercosis using specific monoclonal antibody against cysticercus antigen (CCyl) based on inhibitive ELISA was reported. The circulating antigens were detected in the sera from 83 patients with cysticercosis, the positive rate being 71.1%. The range of the detectable serum antigen concentrations was 0.16-128 micrograms/ml. In 41 cases of cysticercosis patients, circulating antigens were determined in both sera and cerebrospinal fluids, the positive rates being 68.3% and 78% respectively, the total positive rate being 90.2%. In 114 sera from normal persons, circulating antigen was absent. In 30 sera from patients with hydatidosis, 30 with clonorchiasis, 20 with schistosomiasis japonica, 24 with paragonimiasis, and 5 sera collected from non-parasitosis patients, serum circulating antigen was not detectable. In another 10 non-parasitosis patients, circulating antigen was not found in cerebrospinal fluid. After chemotherapy for one half to one year, in 21 out of 23 cases of cysticercosis patients, the circulating antigen levels in sera dropped to zero, except for two cases having an antigen level of 0.64 micrograms/ml and 1.6 micrograms/ml, respectively. Our results showed that the determination of the circulating cysticercus antigen was very specific for the diagnosis of active infection of cysticercosis and could be used as a rational tool in monitoring the effectiveness of chemotherapy. PMID- 1873885 TI - [Freeze-etch study on the brush border structure of Cysticercus cellulosae]. AB - The images of C. cellulosae detected by freeze-itch technique were exactly similar to those observed in the thin section. The scolex microtriches might be divided into two parts, a thick proximal portion and a thinner spinal distal end, the former measuring about 0.2-0.4 micron in length, the latter measuring about 1 2 microns in length. On the extracellular surface of the proximal portion of microthrix, 1 or 2 particles could occasionally be seen, while numerous particles appeared on the protoplasmic fracture face (PF face) of the proximal portion. The PF face were closely packed and irregularly distributed with membranous particles, which were spherical or subspherical in shape, measured 0.01-0.02 micron in diameter. The extracellular fracture face (EF face), of proximal portion and all four membranous faces of spinal end were smooth. The tegumentary plasmic membrane was 0.02 micron in thickness, with smooth ES face. The PF face of this membrane packed closely with numerous particles, which were similar with those on the PF face of the microthrix. Numerous globular or discoidal vesicles scattered at random in the tegumentary matrix. Most mitochondria were near the basement membrane of the matrix. In the parenchymal layer, the parenchymal cells, calcareous corpuscles and flame-cells could easily be seen. Most of the calcareous corpuscles and flame-cells were located closely beneath the muscle layer. The flame-cell of C. cellulosae mainly consisted of three portions, cell body, a bundle of cilia and a filtered cell lumen. The flame-cell body had a large nucleus and relatively few cytoplasm with several mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873886 TI - [Observation on the behavior of microfilariae in human filariasis]. AB - A total of 19 female adult filariae containing microfilariae in uteri collected from 25 filariasis patients were examined. Light transmission microscopic observations showed: (1) some of the adult worms entered the lumen of blood vessels by penetrating the venous wall and discharged immature and mature microfilariae and embryos into the blood stream; (2) microfilariae developed into maturation in the uterus of adult female worms, but when the adult worm began to degenerate, the microfilariae did not degenerate concurrently; (3) some microfilariae could form thrombus, inducing the infiltration of segmented neutrophils and eosinophils followed by the formation of granuloma; (4) embryos 8 female adults parasitizing lymphatics were seen to discharge immature microfilariae and ova, which might form emboli after entering the blood stream. PMID- 1873887 TI - [Protoscolicidal effect of some chemical agents and drugs against Echinococcus granulosus]. AB - The present paper reports the protoscolicidal action of hydrastine, ether-acetic acid-ethanol admixture, H2O2, pyquiton and albendazole through in vitro or in vivo exposure, for 15 minutes and transplantation studies. The mortality of protoscolices in vitro and in vivo were 70.2% and 68.9% for 0.3% hydrastine, 56.8% and 56.2% for 10% ether-acetic acid-ethanol admixture, 6.0% and 8.8% for 0.3% H2O2; 6.1% for 0.004% pyquiton in vitro and 5.0% were 10% and 25% for 0.3% hydrastine, 30% and for 0.004% albendazole in vitro. The survival rates after transplantation of protoscolices 37.5% for 10% ether-acetic acid-ethanol admixture, 100% and 95% for 0.3% H2O2 respectively. Disruption of external plasma membrane, hook detachment, sucker deformity of protoscolices exposed to hydrastine were demonstrated by scanning electron microscopy. It is suggested that hydrastine exerts a profound intracellular effect on the protoscolex of E. granulosus of sheep and man, and might be a promising protoscolicide as adjuvant to hydatid surgery. PMID- 1873889 TI - [Preliminary investigation of liver alveolar echinococcosis and liver cystic, echinococcosis in Xiji County, Ningxia]. AB - This article reports on the result of an investigation on the prevalence of liver alveolar echinococcosis (LAE) and liver cystic echinococcosis (LCE) in the peasants and the residents of Xiji County, Ningxia Hui Autonomous Region. Among 2,389 selected persons examined with B-ultrasound, 197 cases were diagnosed to have LAE or LCE; the prevalence being 8.2%. Of the 197 cases, 141 (5.9%) had LAE; 56 (2.3%) had LCE. Among 1,413 peasants, 9.7% had LAE; 3.8% had LCE. Among 976 residents, 0.4% had LAE, 0.2% had LCE. Obviously, the peasants were more prone to be infected with the disease, suggesting LAE had much to do with the job of hunting the fox and capturing the Citellus dauricus, while the infectious source of LCE was mainly the domestic dog. PMID- 1873888 TI - [Eighty cases of alveolar hydatid disease treated with albendazole]. AB - Alveolar hydatid disease occurs frequently in Xiji County of Ningxia. 80 cases of the disease were treated orally with albendazole from 1985 to 1988 and the short term results proved satisfactory. The treatment consisted of two groups. Group I included 72 cases which were orally given 8-10 mg/kg.d of albendazole 2 to 3 times a day after each meal for 30 days and then stop taking the medicine for 10 days as one treatment course. The treatment continued 3-12 months comprising about 24 courses were given with the highest dosage of 412g. Group II included 8 cases who were given 15.6-20 mg/kg.d of the medicine for 14 days (one course) and every two weeks with a 10 days interval. The treatment of group II continued 3-6 months which totalled 19-24 courses with the highest dosage of 270g. All the treated patients tolerate well except that a few of them felt giddy and had diarrhoea which disappeared after the withdrawal of medicine. Through 3-5 years, follow-up observation, it was found that the gener alsymptoms of the treated patients improved and their body weight increased by 2-9.5 kg, some of them could take part in light physical labour. The jaundice index in 80% of them returned to normal. SGPT in 86.4% decreased to within normal range. The enlarged livers in half of the patients decreased by 1-6 cm. 23.7% of the patients were reexamined by B ultrasound scanning which revealed that their enlarged liver reduced in size while the liquifaction area and the shadows of calcification in the livers in 42.5% patients increased obviously. PMID- 1873890 TI - [Advances in filariasis control and research in China during 1986-1990. National Technical Steering Group for Filariasis Control and Research, MOPH]. AB - Based upon the statistical data during 1986-1990 from provincial, regional or municipal institutions involved in the control and research of filariasis, important achievement in filariasis control has been achieved since 1986. During the 5 years, 22,350,772 person were blood-examined, among them, 268,034 were found to be microfilaria positive; a total of 78,550,945 man/times of treatment with DEC were given (including administration of DEC-medicated salt). Till the end of 1990, filariasis has been basically eliminated in 823 counties/cities out of the 864 endemic counties/cities, and has been basically eliminated in 12 endemic provinces, one autonomous region and one municipality. Thus far, filariasis is still prevalent in 41 counties/cities of Anhui province. Parasitological, serological and entomological monitoring on filariasis is being executed according to the "Technical scheme for filariasis surveillance in areas where the disease has been basically eliminated" formulated by the Ministry of Public Health. The preliminary results of longitudinal surveillance indicated that the decline of microfilaremia rate and the absence of resurgence coincided with the decrease in antibody titre in the population by IFAT. The progress of research work dealing with the transmission potential in areas where filariasis had been under control, the methods of immunodiagnosis and the treatment of patients with clinical signs was also reviewed. PMID- 1873891 TI - [Detection of Plasmodium falciparum using the plasmid Pf rep 20 probe (preliminary report)]. AB - A cloned repetitive DNA sequence (rep 20) labeled with 32P was evaluated as diagnostic probe for P. falciparum in 39 blood samples from Hainan and Yunan provinces. Its specificity and sensitivity were studied and compared with total genomic DNA probe isolated from P. f. Hainan Fcc1/HN isolate. The pPF rep 20 probe recognized the DNA of P. f. Hainan, Yunnan and Anhui isolates, but did not hybridize with the DNA of P. vivax, P. cynomolgi, P. knowlesi and P. yoelii. The genomic probe hybridized with the DNA of 3 isolates and cross-hybridized with the DNA of all the other Plasmodium species tested, but did not hybridize with host DNA. The plasmid rep 20 probe was able to detect parasitemia level of 0.001% in 20 microliters blood from culture and 10pg DNA of 3 P. f. isolates after 3 days film exposure. It could hybridize with the blood samples of P. f. patients from Hainan and Yunnan with a sensitivity of 95% (37/39). The genomic probe could detect the same parasitemia and DNA levels as plasmid rep 20 probe for Yunnan and Anhui isolates, and 0.0001% parasitemia and 1 pg DNA for Hainan isolate. It had a sensitivity of 97% (38/39) when used to detect patient samples. The results indicated that plasmid rep 20 probe was specific and rather sensitive to DNA of P. falciparum isolates from China and may be useful in epidemiological studies. PMID- 1873892 TI - [Anti-antibody responses of rabbit to mouse monoclonal antibody against schistosome "target antigen"]. AB - The supernatant of protective McAb (isotype IgG2a) secreted by 1E2 hybridoma line was purified by protein A-sepharose CL-4B column and rabbits were immunized with purified 1E2 McAb. Dot-ELISA, immunodiffusion assay, Western blotting and ELISA were used to observe the presence of anti-McAb and anti-anti-McAb. The main results are: 1. anti-McAb antibody could be detected as early as 20 days post immunization in the immune sera and would be decreased gradually without boosting; otherwise, it would be increased quickly and the titers of anti-McAb were increased within 5 days post-boosting and could be maintained at a plateau for 30-50 days, and then decreased gradually to the normal; 2. there were different anti-anti-McAbs in the immune sera. Anti-anti-McAb, like anti-anti idiotype antibody, can recognize different schistosome antigens and 90, 68 or 45 kDa antigenic determinants. The level of anti-anti-McAbs varied from titers 1:100 to 1:1600 at different time post-immunization with 1E2. The results provide evidence to understand the appearance of anti-McAb antibody and the way to develop anti-idiotype and anti-anti-idiotype McAb for research purpose. PMID- 1873893 TI - [Construction of Echinococcus granulosus genomic library]. AB - Using EMBL3 phage DNA as a vector, a perfect genomic library of Echinococcus granulosus from sheep from Xinjiang has been constructed, which contains 1.2 x 10(6) independent recombinants. The main procedure of construction comprised: 1. extraction of Echinococcus granulosus genomic DNA, 2. partial digestion of the extracted E. granulosus genomic DNA with restriction enzyme Sau3Al, 3. harvest of 15-23 kb DNA fragments by electric elution equipment, 4. preparation of EMBL3 phage vector DNA, 5. cleavage of EMBL3 vector DNA with two restriction enzymes Bam HI and Eco RI to remove the central fragment, 6. ligation of the harvested 15 23 kb E. granulosus genomic DNA and the cleavaged vector DNA with T4 DNA ligase, 7. the package reaction of ligated recombinant DNA in vitro with the package protein and with Q359 strain (Spi-) to screen recombinants, 8. identification of the genomic library, 9. hybridization in situ by pSM889 probe, obtaining 6 positive recombinant clones. It was estimated that the E. granulosus genome was about 1.5 x 10(8) bp. A perfect E.g. genomic library is expected to contain 4.6 x 10(4) independent recombinants at minimum. The constructed genomic library has enough independent recombinants (1.2 x 10(6)). This is the first time to establish an E. granulosus genomic library in China. Previous work showed that there existed differences in many aspects, including pathogenicity, among various isolates of E. granulosus from different hosts and areas. We plan to employ this library to screen the E. granulosus intraspecies DNA probe by hybridization in situ. This kind of probe is envisaged to be of advantage for epidemiological investigation of the hydatid disease in China. It also provides a base for researching E. granulosus at the molecular level. PMID- 1873894 TI - [Analysing the effects of tooth extraction under acupuncture anesthesia in 825 cases of senior]. AB - It has been found that the effects of tooth extraction under acupuncture anesthesia (AA) for the old patients are generally quite good. In order to verify this result, the authors had statistically analysed 825 cases aged over 60 years (Group A) and equal quantity whose age were between 18-40 years old (Group B) out of more than 4000 cases whose records of AA were rather completely during 1973 to 1988. 1. There was no significant difference under AA for different sexes. 2. The differences of the excellent rate of AA between Group A and Group B were extremely evident either in the positions of the tooth or the reason of tooth extraction. The former was 89.04% and the latter 76.20% (P less than 0.005). 3. Although a low rate in excellence of tooth extraction under simple AA (only 75.58%), not so good as the effect by AAA (an average about 88.21%), the simple AA was more common and more easier to be accepted by patients. 4. Tooth extraction under AA has been proved to be safe, effective and without any complications. 5. The reasons for the senior to extract their teeth were almost for the broken crowns and of roots or the purposes of prosthetic restoration. Even though the pain thresholds in the senior were commonly higher. It is still an important factor of the good effect and good rate of tooth extraction under AA. Referring to the statistics in this study the authors suggest that the hospitals which can use the AA for tooth extraction adopt the method as the first choice of anesthesia method to the senior who intends to accept it. PMID- 1873895 TI - [Effects of stimulating periaqueductal gray on the nociceptive neuron discharges of post-thalamic nucleus evoked by stimulation of splanchnic nerve in cats]. AB - The effects of stimulating periaqueductal gray (PAG) on the nociceptive neuron discharges of pronucleus evoked by stimulating the splanchnic nerve in cats were studied. The two kinds of inhibitory action were observed. One was called early phase or prompt inhibition phase which occurred within 30 ms to 150 ms after stimulation of PAG. The other was called slow-pase or sustained inhibition which occurred from a few minutes to more than ten minutes after the stimulation of PAG. The results showed that PAG played an important role in the analgesia of visceral pain. Both kinds of inhibition may be blocked by naloxone, this suggests that endogenous opiate like substances involved in these inhibitory processes caused by stimulating role in the inhibitory effect of PAG. PMID- 1873896 TI - An analysis of neuronal responses in nucleus centrum medianum to electrical stimulation of the superficial peroneal nerve. AB - Excitatory and inhibitory responses recorded extracellularly in neurons at various levels of the central nervous system induced by electrical noxious stimulation of peripheral nerves were frequently reported in studies on the mechanisms of acupuncture analgesia. However, the correlation between the responses and excitation of distinct afferent fibers was rarely investigated. The question whether the responses mentioned above are truly nociceptive in property is of significance to answer, and this is what we want to clarify in the present study. Sixty five neurons responding to electrical stimulation of the left superficial peroneal nerve were extracellularly recorded in the nucleus centrum medianum (CM) contralateral to the stimulation in 34 cats paralyzed with gallamine triethiodide and ventilated artificially under anaesthetics. Peristimulus histograms of the responses of CM neurons were plotted correspondingly, to the excitation of A delta and C-fibers, which was monitored by means of compound action potentials. To identify the nociceptive property of the responses ketamine or morphine was intravenously administered in some cases, capsaicin was topically applied at the superficial peroneal nerve proximal to the stimulated location in a few cases. Besides, the effect of electroacupuncture (EA) at Zusanli (St36) and Huantiao (GB30) points on the responses was observed. A total of 65 CM neurons recorded included 55 excited and 10 inhibited neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873897 TI - [Effects of noxious stimuli on the discharges of pain-excitation neurons and pain inhibition neurons in the nucleus ventralis posterolalis of thalamus in the rat and a modulating action of electroacupuncture on its electric activities]. AB - The somatic and visceral noxious stimuli could simultaneously induce the increase of discharges of pain-excitation neurons (PEN) and the decrease of discharges of pain-inhibition neurons (PIN) in the Nucleus Ventralis posterolalis (VPL) of thalamus in the rat, and the electric activities of the two kinds of neurons cooperated each other. By the injection of morphine (5 mg/kg) and the electroacupuncture of "zusanli", the discharges of PEN were reduced and the discharges of PIN were enhanced. The results suggested that VPL of thalamus in the rat be involved in the modulating action on pain sensation and the analgesic effects of morphine and electroacupuncture by the simultaneous electric activities of PEN and PIN in VPL. PMID- 1873898 TI - [Effect of prefrontal cortex stimulation on the activity of pain-related neurons in parafascicular nucleus of thalamus in rats]. AB - The effects of PFC stimulation on spontaneous and evoked discharges of neurons of parafascicular nucleus of thalamus were observed in rats. The results show that after PFC stimulation spontaneous of 78.7% PEN (48/61) and evoked discharges on noxious stimulation of 76.6% PEN (46/60) were decreased; spontaneous discharges of 72% PIN (18/25) were increased; inhibition response on noxious stimulation of 70.8% PIN (17/24) were decreased; and spontaneous discharges of 66.7% CON (6/9) and evoked discharges on noxious stimulation of 55.6% CON (5/9) were decreased. The results suggest that PFC might have analgesia action which was accomplished by modulating electric activities of pain-related neurons of parafascicular nucleus in thalamus. PMID- 1873899 TI - [Effects of electroacupuncture at different points on nociceptive responses of the ventro-basal complex]. AB - The purpose of the present study was to compare the effects of electro acupuncture at different points on nociceptive responses of VB neurons. The experiments were carried out on rats (280-320g) anaesthetized with urethane (19/kg,i.p.). Single unit activities of VB neurons were extracellularly recorded by means of glass microelectrodes. Noxious stimulation was subcutaneously applied at the left ankle joint by inserting two stainless needles. The experiments were divided into three groups: EA. I, EA. II and EA. III. The corresponding points being selected for electroacupuncture in the above three groups were the left "Huantiao" (G30) point, the right "Huantiao" point and the left "Jianlian" (T14) point. The results showed that electroacupuncture at the points in the three groups all could inhibit the nociceptive responses of VB neurons, but electroacupuncture an the left "Huantiao" point (n = 11) was more effective than either at the right "Huantian" point (n = 9) or at the left "Jianliao" point (n = 10). There was a significant difference among the three groups. However, there was no significant difference between EA. II and EA. III. Thus, the results indicate that there is a relative specificity of points in acupuncture analgesia. PMID- 1873900 TI - [The role of paraventricular nucleus of hypothalamus in acupuncture analgesia in rats]. AB - Recent evidence has indicated that vasopressin (VP) can increase the pain threshold. It is not clear whether the paraventricular nucleus (PVN) of hypothalamus, which is one of the main nuclei that secrete VP in brain, is involved in the acupuncture analgesia (AA). The present study was designed to examine the role of PVN in AA. Experiments were carried out on Wistar rats using tail stimulation vocalization test to measure the pain threshold. The acupoints "Renzhong" and "Chengjiang" were selected for electroacupuncture. Electrical stimulation of PVN could increase significantly the pain threshold and enhance the effect of AA. On the contrary, electrolytical lesion of PVN could decrease the effect of AA obviously, which could be recovered by cerebroventricular injection (ICV) of 300 ng of arginine VP. Pretreatment with AVP-antiserum (ICV) could attenuate the effect of AA. These data indicated that PVN plays an important role in pain modulation and in the effect of AA. This role might be mediated by the VP-containing neurons in PVN. PMID- 1873901 TI - [The role of nucleus tractus solitarii (NTS) in acupuncture inhibition of visceral-somatic reflex (VSR)]. AB - Experiments were carried out on 164 rabbits. The transmission of abdominal vagal impulses and the mechanism of inhibitory effect by acupuncture systematically were investigated. 1) Electrical stimulation (single pulse of 20 V, 0.5 ms) of abdominal vagus nerve (AVN) produced two kinds of potential on cervical vagus nerve: the fast wave (10.4-24.4 M/sec) and the slow wave (0.9-1.7 M/sec), the later was more stable. 2) In dorsal medulla oblongata the 'M' shaped evoked potentials with long duration (100 ms or so) were recorded. The results suggest that afferents from AVN are mainly transmitted through the small fibres and multi synaptic connections in Medulla. 3) Out of 301 response units, 281 units (93.6%) concentrated in NTS and adjacent regions. This result was also confirmed by injection of Horseradish Peroxidase (HRP) in the trunk of AVN. 4) On 24 awake rabbits the VSR were elicited by strong stimulation of AVN. Electroacupuncture (EA) on "Zusanli" points inhibited VSR, an effect lasted over 20 min. This inhibitory effect of EA was reversed partly by Naloxone (0.5 mg/kg iv) and was attenuated after lesion (DC 0.5 mA, 1 min.) of NTS. In conclusion, NTS plays an important role in suppression of VSR by EA (P less than 0.01). PMID- 1873902 TI - [The role of midbrain periaqueductal grey in the inhibition of central cardiac ischemia by somatic nerve and its mechanism in rabbits]. AB - Experiments were performed on vagotomized male rabbits weighing 1.8-2.2 kg. Urethane and chloralose were administered intravenously, and were paralyzed by flaxedil. After a cannula was inserted into femoral artery to measure blood pressure, the epicardial electrogram (EECG) was recorded. Then we inserted a bipolar electrode into caudal dorsolateral subdivision of periaqueductal grey (CDL), or dorsomedial hypothalamic nucleus (DMH). In some animals, a microinjecting tube was inserted into CDL for microinjection of enkephalin antibodies. In 12 animals, stimulation of CDL could elicit pressor response and elevation of EECG-ST segment. When stimulating deep peroneal nerve, these two responses were inhibited. In 14 animals, with brainstem transected in P5 level, the stimulation of DPN could not inhibit the presser response induced by CDL, but still inhibited the EECG-ST segment changes. After enkephalin antibodies were injected into CDL, DPN could not inhibited EECG-ST changes. In 4 animals, instead of enkephalin antibodies, rabbit serum had no effects. The unit discharges of 96 neurons in CDL were recorded by glass microelectrodes, among them, 15 neurons could be excited by DMH stimulation. We called these neurons the defence reaction related neurons. Stimulation of DPN or median nerve could inhibit the spontaneous discharge and DMH evoked discharge of these defence reaction related neurons. CONCLUSIONS: 1. DPN stimulation can inhibit the pressor response and cardiac ischemia induced by defence reaction centre in CDL of PAG. The inhibitory effect on cardiac ischemia is still eminently remained after the brainstem is cut in P5 level to eliminate the influence of hypothalamic arcuate nucleus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873903 TI - [Effects of electroacupuncture on epileptiform hippocampal unit activity by intracerebroventricular injection of coriaria lactone]. AB - In our present study we build up a new experimental model in the rat for epilepsy by intracerebroventricular injection of Coriaria Lactone (CL) and examine the effects of electroacupuncture on epileptiform hippocampal unit activity. Three types of hippocampal units responding to CL were observed: a) positive units b) negative units and c) indifferent units. The activity of positive units may be the typical epileptiform hippocampal activity. The positive units can be inhibited by electroacupuncture (EA), while the negative units can be exhilarated by EA. No changes were observed in indifferent units. Inhibitory effects of positive units are different because of using different "acupoints". EA of Du-Mo and Taichong Kunlun in the other side of drug injection were significatively better than Taichong, Kunlun in the same side of drug injection. Effects of Du-Mo was significantly better than the effects of the points on the limb. Parameters of EA are significantly different in other side of limb points for inhibition of positive units: 5 V 1 Hz, 5 V 5 Hz greater than 1 V 5 Hz greater than 1 V 1 Hz. These data indicate that effects of EA are depend on amplitude of EA, and seem not to be concern with frequencies of EA. The amplitude and frequency of hippocampal EEG spikes can be inhibited by EA. The inhibitory role of EA on epileptiform discharges is also discussed in this paper. PMID- 1873904 TI - [Segmental distributions of sensory neurons of the "ganshu", "pishu", "liangmen", "qimen" points and the gallbladder]. AB - One hundred guinea pigs were used. The 10% HRP 50-60 microliters solution was injected into the acupoints of "Gansu", "Pisu", "Liangmen" and "Qimen" of every animal. Moreover, the 10% HRP 80-100 solution was injected into the gallbladder of the another animals too. Under the microscope, observed the segmental distributions of sensory neurons of the four acupoints and the gallbladder. It could be found much clearly that HRP labelled cells were appearing in the spinal ganglions. The above experimental studies showed that there are mutual intersect 5-7 segments between the gallbladder and the "Gansu", "Pisu", "Liangmen" and "Qimen" four acupoints. It is probable that the mutual intersect is the neuroanatomic foundation of acupuncture and moxibustion to inhibit the formation of bilirubin gallstones. PMID- 1873905 TI - [The study on calcium ion concentration specificity in meridian and acupoint in rabbit]. AB - Ion selected "Acupuncture electrode" was introduced for detection of calcium ion concentration in meridians and acupoints in rabbit. It was demonstrated that the calcium ion concentration was significant higher than that in the location of non meridian and non-acupoint. This is the first and important finding of physicochemical characteristics of meridians. PMID- 1873906 TI - [The regulating effect of electroacupuncture on gastroenteric electric activity in guinea pigs of peripheral vomiting]. AB - Acute experiments were performed on 20 guinea pigs. The animals were divided at random into four groups of five each: the non-acupuncture group for control and three electroacupuncture groups (EA-I, EA-II, EA-III). Four pairs of platinum wire electrodes were implanted under serosa of the antrum and corpus, duodenum, jejunum. The gastroenteric electric activity (GEA) was recorded in conscious and fasting state. Needling was applied at position 1 cm below the knee, corresponding to Zusanli. The peripheral vomiting model was established by infusion of CuSO4 into the stomach. Observation was made with regard to latency of vomiting induced by infusion of CuSO4, duration of the symptom, number of fits in the first five minutes after the attack began, and the variation of amplitude and frequency of GEA. The results were as follows: (1) The GEA of normal guinea pigs showed regular cyclic changes. After latency of 3.7 seconds following the infusion, symptom of vomiting began appear. The GEA returned to normal after latency of 60 minutes. (2) During vomiting, the GEA was characterized by a series of spikes which were seen more obviously in the antrum and corpus; during serious fits of vomiting, duodenum and jejunum were involved. The GEA showed disordered and quicker rhythm with higher amplitude and frequency. (3) EA could not affect the latency of the peripheral vomiting, but it could shorten the duration of the symptom. Results of group EA-II (p less than 0.001) showed EA could reduce the number of fits during the first five minutes; results of group EA-I (p less than 0.01) showed that EA could lower the amplitude and frequency of the GEA (p less than 0.05) that rose during vomiting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873907 TI - [The thermographic observation of the relationship between the retention of acupuncture needles and the effect of nose temperatures]. AB - This is an observation of the relationship between the retention of acupuncture needles and its effect on nose temperature in seventy-four patients with facial nerve paralysis. The patients were divided into five groups according to the period of retention of needles: no retention, retention for ten, twenty, thirty and fourty minutes. Every group consisted twenty cases. The results showed that (a) the nose temperature lowered after acupuncture immediately; (b) then it rose and reached to the maximum at twenty minutes after acupuncture, then lowered again; (c) for the group of no retention and retention for ten and twenty minutes, the temperature rose again during thirty to fourty minutes after acupuncture, for the group of retention for thirty or fourty minutes, however, without these phenomena; (d) the general tendency was that the change of temperature was bigger but lasting for shorter period in the groups of retention for longer time than that in the groups of retention for shorter time. These results verified that some theories in ancient books about the retention of acupuncture needles are scientific. PMID- 1873908 TI - [Experimental acupuncturology and its role in acupuncture education--suggestion offering the course of experimental acupuncture in acupuncture education]. AB - Experimental Acupuncturology is a new subject which probes the channel and principle of acupuncture with the help of modern scientific technique and experimental method. In channel research, the basic responsibility of Experimental Acupuncturology is to expand the essence of the channel. For nearly half a century, the research has been concentrated mainly on the channel detection, the phenomena of channels and the relationship between channel-point and viscera, etc. In the research on the principle of acupuncture, Experimental Acupuncturology has accumulated a lot of information to prove that therapeutic effect of acupuncture is credible. The effect of acupuncture is influenced by many factors. Thus, it is also one of the basic tasks for Experimental Acupuncturology to programme the experimental procedure according to the principles of diagnosis and treatment based on an overall analysis of symptoms and signs, so that the best wiring scheme can be chosen out. Summarily, Experimental Acupuncturology has, at beast, three important significances in training modern specialists of acupuncture medicine. Firstly, it can make it possible for students to get deeper understanding on the thought of traditional acupuncture and realize the advantage of acupuncture, thus, encourage their faith on this medical means. Secondly, it can enrich the contents of acupuncture medicine and broaden the outlook of students, because it introduces modern science, technology and experimental method into traditional theory. Finally, it can train students' ability in scientific researches through strengthening the practicability of acupuncture. Therefore, its active significance in acupuncture education has been granted by acupuncture specialists in our country. Nowadays, more and more colleges of TCM has offered this subject which were welcome widely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1873909 TI - A simple micromethod for rapid assessment of the distribution of apolipoprotein C isoforms in very-low-density lipoprotein. AB - A simple and rapid isoelectric focusing method for quantifying Apo C isoforms of triglyceride-rich lipoprotein was developed. The very-low-density lipoprotein (VLDL) was isolated from 100 microL of EDTA plasma using a Beckman Airfuge ultracentrifuge. The delipidated VLDL was applied to an ultrathin flat acrylamide gel, and focused using a Bio-Rad Mini IEF Cell, for 1.5 h at a maximum of 500 V. Apo CII and Apo CIII in VLDL were resolved into four major bands, CIII0 (PI 4.91), CII (PI 4.78), CIII1 (PI 4.72), and CIII2 (PI 4.53). The method demonstrated within-run and between-run CVs of 2.7% to 11.9% and 4.4% to 12.2%, respectively. The relative percentage of C apoproteins and the ratio of CII to CIII found in VLDL from plasma of normal, chronic renal failure, and hyperlipidemic subjects agreed with previously published data. PMID- 1873910 TI - Defective expression of alpha-L-fucosidase by lymphoid cells of a fucosidosis patient. AB - Fucosidosis is an inherited lysosomal storage disease due to a deficiency of alpha-L-fucosidase activity. Exponentially growing lymphoid cell cultures from a fucosidosis patient (JH) had 16-fold lower extracellular alpha-L-fucosidase protein and 72-fold lower intracellular alpha-L-fucosidase protein with negligible catalytic activity as compared with the mean of 19 control cultures. The percentage of total alpha-L-fucosidase protein released extracellularly by JH cells was 71% as compared with 35% +/- 9% for control cells. During a 1.5 h pulse with 35S-methionine, alpha-L-fucosidase was synthesized by JH cells as an intracellular doublet with Mr of 58,000 and 56,000 and by control cells as an intracellular form with Mr = 58,000. During a subsequent 21 h chase with unlabeled methionine, JH alpha-L-fucosidase was entirely secreted. In contrast, only 25%-30% of control enzyme was secreted with the remainder retained intracellularly. Thus, JH lymphoid cells synthesized a reduced amount of alpha-L fucosidase that was catalytically inefficient and was hypersecreted. Treatment of JH alpha-L-fucosidase with N-glycanase produced polypeptide chains with Mr of 52,000 and 54,000. Previously, treatment of control alpha-L-fucosidase with N glycancase produced a single polypeptide chain with Mr of 52,000 (Biochem Genet 1988; 26: 401-20). The doublet polypeptide chains of alpha-L-fucosidase in JH cultures may represent expression of two distinct allelic forms of mutant alpha-L fucosidase. PMID- 1873911 TI - An enzyme-linked immunosorbent assay (ELISA) for the detection and quantitation of the tumor marker 1-methylinosine in human urine. AB - A highly sensitive enzyme-linked immunoassay (ELISA) was developed to detect and quantify the tumor marker, 1-methylinosine (m1I), in human urine. The rabbit antisera was highly specific for m1I with negligible or no inhibition by other nucleosides excreted into urine. Using the competitive ELISA, nanogram amounts of m1I were easily measured directly in urine. The assay agreed with our previous hplc analysis of m1I in urine for identifying those individuals with chronic myelogenous leukemia. Thus, this assay should greatly facilitate the quantitation of m1I as a tumor marker. PMID- 1873912 TI - Lipoprotein-cyclodextrin interaction. AB - Interaction of cyclodextrins with native and isolated lipoproteins was studied by electrophoretic and spectroscopic means. Reaction between these two biomolecules resulted in the formation of soluble and insoluble complexes. Cyclodextrin mediated precipitation of lipoproteins was strongly affected by the concentration of the oligosaccharide and the presence of guest molecules capable of being entrapped within the cyclodextrin cavity. Lipoprotein precipitation by cyclodextrins was observed under acidic, neutral as well as alkaline conditions. The ionic strength of the medium did not significantly affect this interaction. Under appropriate experimental conditions, most types of cyclodextrins were able to form complexes with the various lipoprotein classes. The ability of cyclodextrins to precipitate lipoproteins was in the order of beta-cyclodextrin greater than alpha-cyclodextrin greater than gamma-cyclodextrin and hydroxyalkylated beta-cyclodextrin. Among the lipoproteins, the order of reactivity with a given cyclodextrin was: low density lipoproteins greater than high density lipoproteins greater than very low density lipoproteins. Competitive studies using L-phenylalanine and methanol, both of which form inclusion complexes with cyclodextrins, reveal that molecular encapsulation plays an important role in the stabilization of beta-cyclodextrin-lipoprotein complexes. The present data also suggests that the binding of cyclodextrins to lipoproteins may involve the formation of exclusion complexes. PMID- 1873913 TI - Platelet activating factor acetylhydrolase activity in the urine of patients with renal disease. AB - Platelet activating factor has been demonstrated in blood and urine and has a broad range of effects on kidney function. The kidney possesses the enzymes responsible for PAF synthesis as well as the specific acetylhydrolase which deactivates PAF. We used a radioactive assay to measure PAF-acetylhydrolase activity in urine samples obtained from normal individuals and patients with various nephropathies. Activity was detected in the majority of normal urines with a mean + 2 SD = 0.70 nmol/30 min/ml. Activity exceeding this value was measured in the urines of 11 of 14 patients with diabetes mellitus, 14 of 22 with glomerulonephritis, and 5 of 16 with hypertensive renal disease. Further study is necessary to relate urine hydrolase activity to specific functional and structural abnormalities of the kidney. PMID- 1873914 TI - Ecdysteroid-like compounds in human urine: they can occur in the absence of any parasitic infection. AB - Ecdysteroids (compounds related to 20-hydroxyecdysone, the insect molting hormone) can appear in the blood and urine of man, as a result of an infection with helminths. It has been assumed that the products are released by parasites. However, we found that the phenomenon is not restricted to helminthiases, but is widely spread among patients suffering from various diseases or injuries: twenty percent of hospital in-patients had urine highly positive in our test. This was due to the appearance of immunoreactive compounds not found in healthy people. Among them, one was remarkable for being largely predominant in some patients. These findings indicate that the origin and significance of ecdysteroids in man should be reconsidered. Since they appear only in association with severe pathological conditions, they could be of potential interest as a clinical marker. PMID- 1873915 TI - Changes in ceruloplasmin activity and lactate concentration in patients at high risk of acute organ system failure. AB - In 241 critically ill patients at a high risk of acute organ system failure (OSF) the activity of ceruloplasmin (CPL) and the concentration of lactate in blood was measured. In patients with acute OSF the lactate concentration is high, and the CPL activity is lower in comparison with patients without OSF. These changes are particularly distinct in nonsurviving patients with OSF. The results are discussed in connection with the development of a tissue oxygen debt and the decrease of antioxidative capacity of blood. PMID- 1873916 TI - Determination of medium chain acyl-CoA dehydrogenase activity in cultured skin fibroblasts using mass spectrometry. AB - Medium chain acyl-CoA dehydrogenase deficiency, a defect of mitochondrial beta oxidation, is one of the most frequently occurring among inborn errors of metabolism. We describe a rapid and sensitive gas chromatographic/mass spectrometric method allowing reliable assessment of medium chain acyl-CoA dehydrogenase activity in cultured skin fibroblasts. We investigated MCAD activity in three presumed medium chain acyl-CoA dehydrogenase deficient (MCADD) patients and 10 control subjects. The medium chain acyl-CoA dehydrogenase activity determined in three patients was 1.0 +/- 0.4 nmol.min-1.mg-1 protein (mean +/- SD; range: 0.6-1.4) and in controls it was 2.8 +/- 1.0 nmol.min-1.mg-1 protein (mean +/- SD; range: 1.6-4.4). PMID- 1873917 TI - Response of urinary angiotensin to challenges of the renin-angiotensin system. AB - Angiotensin has an intrarenal action which may not parallel its action in the general circulation. We investigated whether the urinary excretion rates of angiotensin I and II (UV-AI, UV-AII) can be used as a marker of renal production. We therefore measured UV-AI, UV-AII, plasma angiotensin I and II (PAI, PAII), and plasma renin activity (PRA) in healthy subjects under conditions influencing the renin-angiotensin system: captopril injection (n = 7), enalapril treatment (n = 9), furosemide infusion on high and low sodium intake (n = 6), indomethacin treatment (n = 8), and head-out water immersion (three sodium intakes). After captopril (acute) and enalapril (chronic), PAI and PRA increased, PAII decreased, but neither UV-AI nor UV-AII changed. During furosemide infusion, PAI, PAII, PRA, as well as UV-AI and UV-AII increased. During indomethacin treatment, PAI, PAII, and PRA decreased, whereas UV-AI and UV-AII did not change consistently. Sodium restriction increased PAI, PAII, and PRA, but did not alter UV-AI and UV-AII. Head-out immersion decreased PAI, PAII, and PRA, but did not change UV-AI and UV AII. The relative constancy of the urinary AI and AII excretion rates makes it doubtful whether urinary angiotensins reflect changes of renal angiotensin production. PMID- 1873918 TI - A gas chromatographic method for the determination of neutral steroid profiles in urine, including studies on the effect of oxytetracycline administration on these profiles in men. AB - A capillary gas chromatographic method for the determination of 'total' metabolic profiles of urinary neutral steroids was developed. The method is based on anion exchange chromatographic separation and purification of monoglucuronide-, monosulphate- and double-conjugated neutral steroids on DEAE-Sephadex A-25 microcolumns and the final analysis of the individual steroids in these conjugate groups is carried out by capillary column gas-liquid chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The method was shown to provide a convenient and accurate determination of total metabolic profiles of neutral steroids in urine and thus, can be used for metabolic studies of steroids and for diagnostic purposes. In the present investigation the effect of a tetracycline antibiotic on the production and metabolism of neutral steroids in men was studied during a 5-day oral administration of oxytetracycline. The results showed that the influence of oxytetracycline on neutral steroids was minor and mainly restricted to the changes in urinary neutral steroid glucuronide excretion. Oxytetracycline decreased the mean daily excretion of total neutral steroid monoglucuronides by 20% and a statistically significant decrease was found in the urinary excretion of 3 alpha-hydroxy-5 beta-androstan-17-one-glucuronide (etiocholanolone, 31%, P less than 0.05), 5 beta-pregnan-3 alpha,20 alpha diolglucuronide (pregnanediol, 32%, P less than 0.05) and corticosteroid glucuronides, including 3 alpha,11 beta,17 alpha,20 beta,21-pentahydroxy-5 beta pregnan- and 3 alpha,17 alpha,20 beta,21-tetrahydroxy-5 beta-pregnan-11-one glucuronides (beta-cortol and beta-cortolone, 36%, P less than 0.05). The reason for this effect is unknown, but may be partly due to inhibition of intestinal hydrolysis of biliary steroid conjugates, which previously was shown to result in an interruption of enterohepatic circulation of steroids and an increased excretion of steroid conjugates by the faecal route. PMID- 1873920 TI - Aids: A ten-year perspective. PMID- 1873919 TI - AIDS: a historical overview. AB - AIDS has been a recognized clinical entity now for just 10 years. In that time in the United States alone, it is estimated that 1 to 2 million people may be infected with HIV. Estimates of numbers infected worldwide are as high as 10 million. Over these 10 years, considerable progress has been made. The disease and all its protean manifestations have been accurately described. How HIV spreads and where it is spreading have been accurately recorded. The cause is known and well understood, with more detailed information available about HIV than about any other virus. Drugs that slow down the replication of HIV have been discovered and are in widespread use. A cure or vaccine, however, seems unlikely in the near future. The major hope for the present would appear to be continued education to prevent the spread of AIDS and better antiviral agents that will keep HIV suppressed and, ideally, soon allow infected individuals to lead a close to-normal lifespan (if treatment is commenced at an early-enough stage in the course of the infection). PMID- 1873921 TI - The human immunodeficiency virus. AB - HIV is a complex retrovirus. Like some other viruses it infects host cells for life, but unlike other viruses it appears to do so every time. Its elaborate genetic regulation enables it to remain relatively dormant, replicating steadily but slowly. On appropriate stimulation, it is capable of explosive up-regulation, releasing high numbers of new infectious virus. It replicates in an error-prone way, constantly changing its structure to improve its infectivity while presenting the host's immune system with a constantly moving target. PMID- 1873922 TI - The immunopathogenesis of AIDS. AB - In summary, the understanding of the pathogenesis of immune dysfunction in HIV infection is incomplete. New mechanisms by which HIV disrupts the immune system through alterations in basic biochemical events in CD4 T cells are continually being discovered. In a positive light, because of the complexity involved in HIV mediated induction of immune suppression, logic suggests there is potential for reversing some of these processes. PMID- 1873923 TI - Monocytes, dendritic cells, and Langerhans cells in human immunodeficiency virus infection. AB - Cells of the immune system are the target of infection with HIV. CD4 + T cells latently carry much of the viral burden in the blood and ultimately are depleted by infection with HIV. In contrast, infected tissue macrophages are long-lived and may serve as a viral reservoir. They are productive of relatively greater quantities of viral message RNA and its transcriptional product, infectious virions. Viral production by both cell types is modulated by environmental cytokines, the availability of which may be modified by the virus itself or by abnormally functioning HIV-infected immune cells. Not all susceptible cells are equally infected; although this phenomenon is not well understood, it has been related in vitro to maturation or differentiation. Blood DC and LC, antigen presenting cells bearing many similarities to cells of the monocyte-macrophage lineage, are susceptible to HIV infection in vitro. Some evidence clearly indicates that, in vivo, epidermal LC may be infected with and productive of HIV and may be depleted or phenotypically altered in the HIV-infected individual. We, and others, have been unable to substantiate these findings by routine techniques used in the identification of HIV-infected macrophages in susceptible tissues, such as the brain, lungs, and lymph nodes (in situ hybridization for HIV-specific mRNA, electron microscopy for typical viral particles, recovery of infectious virus onto target cells, immunohistochemical staining of surface proteins in tissue, and polymerase chain reaction amplification of viral DNA). Evidence for the presence of HIV within the dermis of patients is clear; however, dermis contains a great variety of cell types as well as cells from the peripheral blood. We feel strongly that were the epidermis to harbor virus to any significant degree, it would have been identified by at least some of the methods described earlier. Although it is difficult to reconcile these reported differences, it appears that LC must be infected rarely. LC from lesional and apparently normal skin of HIV-infected individuals do not serve as an important reservoir of infectious HIV. Additionally, the diverse cutaneous manifestations seen in this population cannot be attributed directly to viral presence within the lesions but are more likely to result from the multifacted immunologic disregulation occurring systemically. PMID- 1873924 TI - Natural history of human immunodeficiency virus infection. AB - The natural history of human immunodeficiency virus (HIV) infection is marked by a progressive deterioration of the host immune system and a concomitant increase in host viral burden. The rationale for major HIV disease staging systems is discussed in light of this natural history. The need for early diagnosis and treatment of HIV-infected patients is underscored by the prolonged phase during which patients are simultaneously asymptomatic and infectious. Clinical, immunologic, and virologic markers of disease stage, progression, and response to therapy will require continuing refinement as we better understand the pathobiology of HIV disease. PMID- 1873925 TI - Epidemiology of HIV infection and AIDS in the United States. AB - HIV-1 disease has been recognized as a distinct clinical entity for fewer than 10 years. Yet during that time, the virus has spread around the world and affects people of virtually all ages, genders, sexual behaviors, and geographic regions. In the United States, there have been more than 140,000 individuals diagnosed with AIDS, the clinical end stage of HIV-1 disease, and it is projected that AIDS incidence will accelerate through at least 1993. In the early years of the infection epidemic in the United States, the virus spread rapidly and insidiously, predominantly among homosexual men, intravenous drug users, people with hemophilia, and recipients of infected blood products. Since then, the epidemic has been propagated concurrently with epidemics of drug use (intravenous and noninjectable) and sexually transmitted diseases such as syphilis. Since its beginning, HIV-1 has disproportionately affected members of racial and ethnic minorities, particularly in large cities, where transmission takes place sexually, parenterally, and perinatally. The epidemic of HIV-1 has spread outside of traditional urban epicenters and is more significantly affecting adolescents, women, and heterosexuals. There is a great need for renewed and refocused infection-prevention efforts. Projections of resource and medical service needs should be based on up-to-date and accurate assessments of infection epidemic parameters, including infection prevalence, incidence, and acceleration (changes in epidemic velocity over time) rates. PMID- 1873926 TI - Bacterial, viral, fungal, and parasitic infections in HIV disease and AIDS. AB - Infectious complications are the most common cutaneous manifestations of HIV infection. In this article, the bacterial, viral, fungal, and parasitic infections seen in HIV-infected patients are described and illustrated. The relation of these infections to the overall health of the patient and current therapies that have been found beneficial are outlined. PMID- 1873927 TI - Syphilis and HIV infection. AB - The management of an HIV-infected patient with syphilis is an evolving and difficult area of clinical medicine. Many such patients initially present with dermatologic problems, and the practicing dermatologist must be alert to the variety of presentations syphilis may take in these patients. The role of biopsy with immunofluorescent or Warthin-Starry silver staining is often crucial in correctly diagnosing confusing cases. The treatment of early syphilis in HIV infected patients may need to be more intensive than has previously been recommended, because the immunosuppression induced by HIV can accelerate the pace of the infection and increase the risk of progression to neurosyphilis. After treatment, careful and frequent follow-up is essential so that the often irreversible consequences of late syphilis can be avoided. PMID- 1873928 TI - HIV-related malignancies. AB - Since the recognition of Kaposi's sarcoma as a manifestation of the acquired immunodeficiency syndrome, subsequent malignancies such as non-Hodgkin's B-cell lymphoma and primary central nervous system lymphoma have been found to be associated with individuals infected with the human immunodeficiency virus (HIV). The epidemiology, clinical manifestations, and current concepts of pathogenesis are reviewed in this article. In addition, the relation between HIV and other malignancies, including Hodgkin's lymphoma, T-cell lymphomas, and anorectal carcinoma, is discussed. In general, HIV-related malignancies are more aggressive, respond poorly to treatment, and are associated with an extremely high rate of mortality. PMID- 1873929 TI - Oral manifestations of HIV infection. AB - Oral lesions are frequently seen in association with all stages of infection with the human immunodeficiency virus (HIV). Many of these lesions occur as the first clinical sign of HIV infection. These lesions include candidiasis, hairy leukoplakia, warts, ulcers, and an aggressive form of periodontal disease. Careful oral examination may reveal lesions that alter Centers for Disease Control staging. PMID- 1873930 TI - Papulosquamous disorders associated with human immunodeficiency virus infection. AB - Papulosquamous eruptions are the most frequently seen cutaneous manifestations of human immunodeficiency virus (HIV) infection. Especially common and useful in making a diagnosis of HIV infection are seborrheic dermatitis, xerosis or ichthyosis, and a pruritic or papular eruption. There is some evidence from transgenic mice studies that the transactivating gene TAT and the HIV provirus may produce epidermal hyperplasia, either directly or through cytokine production, without associated immunodeficiency. The association of certain papulosquamous diseases, especially psoriasis, with HIV has opened up new avenues of research on pathogenesis of hyperproliferative skin disease. PMID- 1873931 TI - Cutaneous manifestations of HIV infection in children. AB - The vast majority of children with infection with the human immunodeficiency virus (HIV) develop some form of mucocutaneous disease during the course of their illness. Candidal, fungal, bacterial, and viral infections of the skin and mucous membranes tend to be more severe and less responsive to therapy than in the healthy child. Children with HIV infection are also at risk for drug eruptions, seborrheic dermatitis, and several other inflammatory disorders of the skin. An understanding of the cutaneous manifestations of HIV infection may aid in the early diagnosis and appropriate treatment of this disease. PMID- 1873932 TI - Histopathologic features of HIV-associated skin disease. AB - The cutaneous lesions that occur in individuals infected with the human immunodeficiency virus are often more severe than those in normal individuals. Of great importance is the fact that many common disorders may show atypical clinical and histologic features, which can lead to misdiagnosis and delayed or inadequate therapy. Therefore, knowledge of pitfalls combined with adequate biopsy and thorough histologic evaluation give the greatest chances of successful diagnosis and treatment. PMID- 1873933 TI - AIDS and infection control in dermatologic surgery. AB - In summary, the AIDS epidemic has created many new questions for the dermatologist, with no clear answers. As dermatologic surgery is increasing in most dermatology practices, the dermatologic surgeon must take a careful look at his office techniques and educate his personnel on the proper handling of blood and body fluids. The medical and ethical issues raised by the AIDS epidemic are complex, with new issues being raised as more is learned about the disease. The adage "do no harm" should be kept in mind in the counseling, diagnosis, and treatment of HIV-infected individuals. PMID- 1873934 TI - Future issues in AIDS. PMID- 1873935 TI - Antihistamine update. AB - Antihistamines are a diverse group of drugs, each possessing the ability to inhibit various actions of histamine. Because they act principally through competitive inhibition of the histamine receptor, they are helpful as a means of preventing rather than reversing these actions. As a result of a resurgence of interest in antihistamine therapy during the past decade, a new class of H1 blockers, clinically devoid of sedative and anticholinergic effects, has evolved. Thus, the choice of antihistamine can now be based on the side effects profile as well as the clinical profile. As we continue to develop a better understanding of these newer agents, we will be able to select more rationally the antihistaminic agent most appropriate to the specific disorder. Used judiciously, the antihistamines available today have a broad application of therapeutic uses, with few significant side effects. PMID- 1873936 TI - Effect of dietary proteins and lipids in patients with membranous nephropathy and nephrotic syndrome. AB - Twenty-four patients with idiopathic membranous nephropathy, long-lasting nephrotic syndrome and serum creatinine less than 2 mg/dl ate sequentially, in a randomized cross-over design, a normal protein diet containing 1.1 +/- 0.3 g/kg/day of proteins and a low protein diet containing 0.7 +/- 0.1 g/kg/day of protein, each diet for a period of 3 months. Both diets were low in fat (less than 30% of total calories) and cholesterol (less than 200 mg/day) content and rich in polyunsaturated fatty acids and in linoleic acid (10% of energy). Random assignment to one of the two 3 month diet periods was done after a RUN-IN period of at least one month on the hypolipidic normal protein diet. Glomerular filtration rate (inulin clearance), 24 hour urinary protein loss and serum albumin concentration did not significantly differ at the end of the two diet periods, indicating that long-term restriction of protein intake does not modify GFR or urinary protein loss in nephrotic patients. Serum total and LDL cholesterol and daily proteinuria were significantly lower at the end of both diet periods than at the beginning and at the end of the RUN-IN period. We suggest that these changes were a consequence of the manipulation of dietary fat intake. PMID- 1873937 TI - Crescentic glomerulonephritis in Wegener's granulomatosis: morphology, therapy, outcome. AB - Fourteen patients with Wegener's granulomatosis (WG) and severe renal and extrarenal involvement were studied (serum creatinine on admission 5.8 +/- 3.4 mg/dl). Renal histology showed a necrotizing, crescentic glomerulonephritis in all patients. Despite advanced renal disease on admission cyclophosphamide, steroids (in 13 patients) and plasma exchange (in 9 patients) caused a rapid and sustained improvement of renal function. Four patients required intermittent hemodialysis over a period of one week. After 2 weeks of treatment serum creatinine values below 2 mg/dl (n = 4) indicated a nearly complete recovery of renal function in the long-term follow up (mean serum creatinine achieved after 12 months therapy: 1.1 +/- 0.1 mg/dl (n = 4). Therefore serum creatinine values observed after 2 weeks of therapy, appear to be of prognostic value with regard to renal outcome. No relapse of active WG or progressive renal deterioration was observed during follow-up (22 +/- 13 months) except in one patient with persisting renal impairment. Three patients died (staphylococcus sepsis, intracerebral hemorrhage during hypertensive crisis, pulmonary embolism) during the first two months of therapy. The decline of serum creatinine seemed to be a better indicator of successful therapy than the decrease of anticytoplasmatic antibody (ANCA), erythrocyte sedimentation rate (ESR) and hematuria. On admission ANCA titer neither correlated with serum creatinine, the degree of renal involvement, nor was it of prognostic value. ANCA, serum creatinine and hematuria normalized within 2 to 8 months, whereas ESR and proteinuria remained elevated. Our data indicate a good prognosis of WG even with advanced renal involvement and generalized vasculitis provided aggressive treatment is performed early. PMID- 1873938 TI - Very late recurrence of renal vasculitis. AB - We report a case of renal vasculitis with a relapse occurring 9 and a half years after the original presentation. The plasma creatinine six months before relapse was only 118 mumol/l. During the initial illness there was histological evidence of glomerular damage but at the time of relapse renal biopsy showed the remaining glomeruli to be normal with the destructive process causing fibrinoid necrosis of arteries. PMID- 1873939 TI - Glomerular proteinuria as an early sign of renal-transplant rejection. AB - The introduction of cyclosporin gave rise to an additional problem in the surveillance of renal transplant patients, namely the differentiation between cyclosporin toxicity and acute transplant rejection. The development of assays for specific proteins in urine has produced a non-invasive solution to this problem. In 55 renal transplant patients the following proteins were determined daily in 24 h-urine samples: IgG, transferrin (TF), albumin, beta 2-microglobulin (beta 2-MG), retinol binding protein (RBP), alpha 1-microglobulin (alpha 1-MG) and alpha 1-antitrypsin (alpha 1-AT). All proteins were determined quantitatively using immunoluminometric assays and 10 microliters urine in dilutions from 1:1 1:100. The urinary protein excretion was related to the actual creatinine clearance as this index gave the best differentiation between normal and abnormal status. In 24 h-urine, intraindividual peaks of IgG, TF and albumin were seen regularly in acute rejection episodes. However, a peak in the "tubular" proteins (RBP, beta 2-MG, alpha 1-MG) could not be detected. After effective treatment of the rejection episode, the renal function improved and the protein excretion returned to prerejection episode levels. In bacterial infection of the urogenital tract, urinary alpha1-AT levels rose. They returned to normal after successful antibiotic treatment. In two cases of cyclosporin toxicity neither glomerular nor tubular proteins were excreted in abnormal amounts when compared with transplant patients without complications, the only changes being an increase in serum creatinine as a result of reduced renal function. PMID- 1873940 TI - Familial juvenile gouty nephropathy with renal urate hypoexcretion preceding renal disease. AB - This paper reports investigations in a young woman with renal disease and six other seemingly healthy young members of a new kindred (four male:two female) with familial juvenile gouty nephropathy (McKusick 16200). The family had previously been known to have a "familial" renal disease, but came to attention through an isolated episode of gout in the propositus when renal function was already impaired. A reduced GFR was found in three of the other six subjects. Hyperuricemia associated with a grossly reduced fractional uric acid clearance (Cur/Ccr x 100) was present in the propositus and five kindred members, three of whom were children. The finding of this abnormality in two subjects with normal GFR suggests that this apparent hallmark of the disease precedes the onset of renal damage. The results confirm the dominant nature of the disorder, and highlight the need to investigate all kindred members of patients with juvenile gout and renal failure. Early recognition is important, since allopurinol therapy in doses adjusted to the reduced renal function may ameliorate the progression of the renal lesion. PMID- 1873941 TI - Nutritional assessment in anemic hemodialysis patients treated with recombinant human erythropoietin. AB - Nutritional status was assessed in 25 anemic hemodialysis patients before and during erythropoietin treatment. Nutritional assessment included regular blood chemistry determinations, anthropometric measurements, analysis of protein content in skeletal muscle, and estimation of daily protein intake from protein catabolic rate determinations (using urea kinetic modelling) and dialysis efficiency for urea. These measurements were done immediately prior to erythropoietin treatment, after anemia correction and after one year of maintenance erythropoietin treatment. Both relative body weights and subcutaneous fat stores were low at the start, but increased significantly (p less than 0.05) during the study. Sixteen of the 25 patients gained weight and eight patients lost weight. The patients with weight gain had at the start of the study low weight indices (body weight 89.9 +/- 7.6% of ideal body weight, body mass index 20.6 +/- 1.6), significantly (p less than 0.005) lower than the patients with weight loss. Although protein malnutrition was not obvious from arm anthropometrics, alkali soluble protein/DNA ratio or from serum albumin determinations, ASP/DNA ratio, increased in three of five patients investigated after one year on erythropoietin treatment. Neither protein catabolic rate nor dialysis efficiency changed significantly during the study. We conclude that anemia correction with erythropoietin has a positive effect on malnutrition in hemodialysis patients. In patients with underweight, an adjustment of fat stores was initially observed, followed possibly by an improvement in muscle protein content. PMID- 1873942 TI - Uric acid calculus in renal transplant patients treated with cyclosporine. PMID- 1873943 TI - The current status of myelography. PMID- 1873944 TI - A review of false negative mammography in a symptomatic population. AB - A review of the mammograms of 871 patients with breast cancer from a symptomatic clinic performed at the General Hospital, Birmingham between 1980 and 1988 revealed an overall false negative rate of 8.6%. There has been a steady fall in the number of cancers missed per year from the commencement of review, and this reduction has been more consistent with improvements in radiographic equipment and technique, particularly the introduction of a radiographic grid. In half of the cases the tumour was missed because no radiological abnormality was detectable, even on reviewing the films, and this rate has remained remarkably stable over the study period, emphasizing the importance of a clinical examination in symptomatic women. Comparison of the histological diagnoses revealed similar percentages of ductal carcinomas, 89.6% in the true positive group compared with 85% in the false negative group. Of the false negative carcinomas, 5.5% were medullary tumours compared to 0.8% in the true positive group. PMID- 1873945 TI - Tru-Cut biopsy of mediastinal masses guided by real-time sonography. AB - Twenty-five patients with mediastinal masses, arising in the anterior, middle and posterior mediastinum but in contact with the chest wall, underwent ultrasound (US) guided biopsy with a Tru-Cut needle to obtain a core biopsy specimen from the mass. In all these patients adequate tissue was obtained for a histopathological diagnosis and no major complications were observed. The advantage of core biopsy over fine needle aspiration cytology in mediastinal masses is that accurate histopathological differentiation, and classification of carcinomas and lymphomas is possible. The advantage of performing real-time US guided biopsy is that puncture of the lung and mediastinal vascular structures is avoided. PMID- 1873946 TI - High resolution computed tomography in adult cystic fibrosis patients with mild lung disease. AB - Chest radiography and high resolution computed tomography (HRCT) were used to evaluate the degree of lung involvement in 38 adult cystic fibrosis patients with unusually mild pulmonary disease. Abnormal features were present on the chest radiograph and/or high resolution CT scans of 35 patients, while in three patients both investigations were normal. Thickening of the wall of proximal right upper lobe bronchi was the earliest abnormal feature on HRCT. The commonest abnormal feature in these patients, including those whose chest radiograph was normal, was mild, uniform dilatation of proximal bronchi. The lumen dilatation was always less marked than the degree of thickening. Ten of the patients were first diagnosed in adult life. Although HRCT scans were normal in two of these patients, there were features suggestive of early pulmonary disease in the remaining eight. PMID- 1873947 TI - The role of magnetic resonance imaging in cystic fibrosis. AB - Magnetic resonance imaging (MRI) of the chest was performed on eight patients with known cystic fibrosis. Comparison was made with the findings on plain chest radiographs. MRI shows a greater extent of disease than that predicted by the chest films alone and clearly demonstrates peribronchial thickening and mucoid impacted bronchi. It also distinguishes between hilar lymphadenopathy and enlarged proximal pulmonary vessels as the cause of prominent hilar shadows without the need for contrast injection. PMID- 1873948 TI - Comparison of left coronary and laevo-phase pulmonary angiograms in detecting left atrial thrombi in rheumatic mitral stenosis. AB - We have compared the diagnostic accuracy of left coronary and laevo-phase pulmonary angiograms in detecting left atrial thrombi in 27 consecutive patients with rheumatic mitral stenosis who underwent both these procedures prior to open heart surgery. In 10 patients, both procedures were 'positive' for thrombus, confirmed at subsequent surgery in all instances (true positive). Both procedures were negative for thrombus in 11 patients, and none of these patients showed thrombi at subsequent surgery (true negative). Left coronary angiography only was positive for thrombus in one patient in whom no thrombus was found at surgery. Laevo-phase pulmonary angiography only was positive for thrombus in five patients, two of whom had thrombus at subsequent surgery. The sensitivity, specificity and predictive accuracy of left coronary angiogram were 83.3% and 93.3% and 90.9% and that of laevo-phase pulmonary angiogram 100%, 80% and 80% respectively. Laevo-phase pulmonary angiograms showed higher sensitivity and left coronary angiograms showed higher specificity for angiographic diagnosis. However, the differences were found to be statistically insignificant. Angiography is a reliable method for detecting left atrial thrombi if both left coronary and pulmonary angiograms are performed and both procedures are positive or negative for thrombus. PMID- 1873949 TI - Malignant 'angiodysplasia'. AB - Four patients with chronic gastrointestinal blood loss of obscure aetiology were investigated by visceral angiography. All showed angiographic abnormalities in the caecum with characteristic features seen in angiodysplasia as well as other conditions such as inflammatory bowel disease, carcinoma. All four patients had a malignant cause for their angiographic appearance. This paper stresses the importance of reviewing previous examinations before accepting a diagnosis of angiodysplasia. The angiographic features of contrast pooling on the anti mesenteric border of the caecum or ascending colon, a dilated intramural vein and early filling of a draining vein imply that serious pathology is present. PMID- 1873950 TI - Diagnosis of the peripheral cavernous haemangioma: comparison of ultrasound, CT and RBC scintigraphy. AB - Thirty-six patients in whom peripheral cavernous haemangioma was clinically suspected were examined by 99mTc red blood cell scintigraphy. Twenty-five of these patients had a palpable lump, and they also underwent an ultrasound examination. Seven patients also had computed tomography and angiography was performed in one patient prior to surgery. Twenty-nine patients had positive scintigrams showing 35 haemangiomas. The ultrasound features were variable and of little value except in anatomical localization. Computed tomography did not add significant extra information. We conclude that 99mTc red blood cell scintigraphy is the preferred diagnostic technique in the investigation of suspected peripheral haemangiomas. PMID- 1873951 TI - The clinical importance of a thick-walled, tender gall-bladder without stones on ultrasonography. AB - Ultrasound examinations of 563 patients with right upper quadrant pain and a clinical suspicion of acute cholecystitis were reviewed. In 31 patients, a tender, dilated gall-bladder with a thick (more than 4 mm) partly hypoechoic wall without any detectable calculi was found on the emergency examination. This was interpreted as due to acute acalculous cholecystitis. None of the patients was critically ill. Twenty-one of the patients had follow-up studies with either oral cholecystography, cholangiography, or ultrasound. Fourteen of the 21 had gall bladder calculi while seven did not. These seven patients presumably represent the true frequency (1.2%) of acute acalculous cholecystitis in this clinical setting. In five other patients with an initial diagnosis of acute acalculous cholecystitis the gall-bladder wall thickening probably was secondary to concomitant pancreatitis, appendicitis, hepatitis or peptic ulcer disease. A meticulous and careful search for gall-bladder calculi should be performed in the presence of a dilated, tender thick-walled gall-bladder. PMID- 1873952 TI - Echogenic rings--an ultrasound sign of early nephrocalcinosis. AB - Echogenic rings in the periphery of renal pyramids were seen in the kidneys of six patients. This appearance is described and is correlated with abdominal radiography or computed tomography (CT) scans, serum calcium levels and, in one patient, autopsy. The findings suggest that echogenic rings are one of the earliest signs of nephrocalcinosis even in the absence of plain radiographic changes. PMID- 1873953 TI - Neonatal renal venous thrombosis: sequential ultrasonic appearances. AB - The ultrasonic appearances of three cases of renal venous thrombosis are shown. Initially the kidney is enlarged, echogenic and shows echogenic streaking that has a vascular or perivascular distribution. Subsequently thrombosis of renal veins or the inferior vena cava may be demonstrated and ultimately the kidney may recover or atrophy. The ultrasonic appearances will depend on the severity of the thrombosis and the stage at which the examination is performed. PMID- 1873954 TI - The use of coronal computed tomography in the evaluation of Kienbock's disease. AB - In a prospective study of 12 consecutive patients with Kienbock's disease, direct coronal CT of the wrist was more sensitive than plain films and plain film tomography in demonstrating structural change including sclerosis, compression and fractures of the lunate. Fractures are more common in Kienbock's disease than previously reported. Earlier detection of fractures by CT, before collapse of the lunate occurs, may allow treatment to prevent the collapse. PMID- 1873955 TI - Case report: hepatic and splenic calcification due to amyloid. AB - A case of marked hepatic and splenic calcification due to primary amyloidosis is presented. Although the patient had been treated with continuous ambulatory peritoneal dialysis, there was no evidence of a causal relationship with the calcification. Amyloid is known to have an affinity for calcium, but this radiographic manifestation has not been previously reported. PMID- 1873956 TI - Case report: small bowel histiocytosis-X. AB - A case of histiocytosis-X with gastrointestinal involvement is described in a 4 month-old child presenting with bloody diarrhoea and obstructive symptoms. Diagnosis was made following laparotomy. The child subsequently developed classical multisystem manifestations of the disease. PMID- 1873957 TI - Case report: mammographic and sonographic demonstration of extramedullary haematopoiesis of the breast. AB - A female patient with agnogenic myeloid metaplasia presented with hepatosplenomegaly and a palpable mass in the right breast. Mammography showed an asymmetric pattern of confluent densities and sonography revealed several smooth, homogeneous and echo-poor masses of variable sizes in both breasts. Excision biopsy of the mass in the right breast revealed extramedullary haematopoiesis as did histopathologic examination of the liver and the spleen. The data are discussed with emphasis on the complementary character of both diagnostic modalities and the resemblance to lymphoma of the breast, although the findings are too non-specific to rule out breast carcinoma. Knowledge of the clinical history and histopathology are necessary to make the proper diagnosis. PMID- 1873958 TI - Diagnostic radiologists and nuclear medicine. PMID- 1873959 TI - Colorado Medical Society physician's directory. PMID- 1873960 TI - Value and limitations of cytologic examinations. PMID- 1873961 TI - Pulmonary cytology. AB - Cytomorphologic criteria for the diagnosis and classification of primary pulmonary carcinomas are described and illustrated. Helpful hints for the differential diagnosis from benign entities and tumors and the cytologic limitations are stated. The fact that pulmonary cytologic interpretations must be made in the light of accurate clinical presentation is emphasized. PMID- 1873962 TI - Cytology of head and neck tumors, liver, and pancreas. AB - The use of fine needle aspiration biopsy helps in reducing the number of thyroidectomies. Cytologic differentiation between cellular adenomas and well differentiated follicular carcinomas is difficult, however; hence, both groups of lesions should be excised. Cytologic diagnosis of the common salivary gland tumors (ie, pleomorphic adenomas and Warthin's tumors) is accurate, but much experience is required for the cytodiagnosis of other tumor types. The majority of liver malignancies is metastatic in origin and poses no diagnostic problems. Pathologists also should be familiar with the cytology of hepatocellular carcinoma as the population of Asian immigrants in North America is increasing. Most of the pancreatic tumors are ductal adenocarcinomas, which can be diagnosed cytologically. Occasionally, atypical ductal epithelium in chronic pancreatitis may mimic malignancy. Cytodiagnosis of nonduct-cell neoplasms of the pancreas requires experience. PMID- 1873963 TI - Aspiration cytology of breast. AB - Most primary malignant epithelial neoplasms and many benign lesions of the breast possess such characteristic cytologic features that they can be diagnosed with certainty by needle aspiration. Because inadequate sampling may result in a false negative cytology diagnosis, the time-tested rule is that a negative cytologic diagnosis is not definitive unless it is fully supported by negative clinical and mammographic findings. PMID- 1873964 TI - Genitourinary cytology. AB - Urinary cytology is a very accurate method of diagnosis of higher grade papillary urothelial carcinomas, carcinoma in situ, and clinically occult tumors of the renal pelvis and ureters. Most lower grade transitional cell neoplasms cannot be diagnosed cytologically with certainty. Fine needle aspiration biopsy (FNAB) of the prostate is an accurate method of diagnosis of malignancy in moderately and poorly differentiated adenocarcinomas; however, the diagnosis of well differentiated tumors is difficult and, in most cases, impossible on FNAB material. FNAB is of value in the diagnosis of renal and testicular neoplasms in selected patients, in monitoring cellular rejection and determination of the impact of therapy in renal transplant patients, and in evaluation of male infertility. The limitations and pitfalls of these diagnostic cytologic methods are discussed. PMID- 1873965 TI - Gastrointestinal cytology. AB - Since the development of the fiberoptic endoscope, laboratories have received cytologic specimens obtained from all segments of the gastrointestinal tract in increasing numbers to identify infectious agents and neoplasms. Adenocarcinomas generally are easily diagnosed and distinguished from reparative atypia, but their precursor lesions, dysplasia and adenomas, provide greater interpretive challenges. The same is true for such entities as malignant lymphomas. Most mesenchymal tumors remain outside the diagnostic capabilities of most cytologists. PMID- 1873966 TI - Effusion cytology. AB - Cytologic evaluation is the best way to detect the presence of malignancy in body cavity fluids. Although a positive diagnosis is highly reliable, a negative result does not rule out a malignant cause. Adenocarcinomas, well-differentiated squamous carcinomas, small-cell carcinomas, malignant melanomas, large-cell lymphomas, and acute leukemias are accurately classified when present in effusions. The definitive diagnosis of malignant mesothelioma, small-cell lymphomas, and chronic leukemias, and subclassification of sarcomas and poorly differentiated neoplasms are difficult and may require additional diagnostic techniques. With a few exceptions, the exact causes of benign effusions cannot be determined by cytologic methods. PMID- 1873967 TI - Cytologic diagnosis of leukemia and lymphoma. Values and limitations. AB - The value and limitations of the cytologic diagnosis of lymphoma and leukemia using a multiparameter approach, including cytomorphology, immunocytochemistry, and flow cytometry, are discussed. Using these diagnostic modalities, most subtypes of lymphoma and leukemia can be classified accurately. The differential diagnoses of the different disease entities also are presented. PMID- 1873968 TI - The detection of positive blood cultures by the BACTEC NR660. The clinical importance of four-day versus seven-day testing. AB - A total of 471 positive blood cultures obtained over a 3-month period were identified and evaluated for day of positivity by the BACTEC NR660. Of all positive blood cultures, 73% (344) were detected within the first 2 days, and 94% (441) were detected through day 4. The proportion of positive cultures detected at day 5 was significantly lower than that at day 4 (p less than 0.01). Patient chart review revealed that two of 30 isolates (0.4% of all positive isolates) identified on days 5-7 were considered clinically significant and would have been missed if cultures would not have been evaluated for seven days. Therefore, very limited additional patient benefit is derived after greater than 4 days of growth and detection by the BACTEC NR660. PMID- 1873969 TI - Multicenter comparison of the high volume (10 ml) NR BACTEC PLUS system and the standard (5 ml) NR BACTEC system. AB - This multicenter study was designed to compare the new BACTEC PLUS system (nonradiometric), which utilizes an 8- to 10-ml blood inoculum in a resin containing medium, to the standard BACTEC (nonradiometric) without resins and 5 ml blood inoculum. There were 12,341 compliant sets studied, yielding 1331 positives, with 1099 sets deemed clinically significant. Overall the BACTEC PLUS showed an enhanced recovery of 33% (p less than 0.001) over its standard counterpart, with significant yield increased in the staphylococci (p less than 0.001), streptococci (p less than 0.002), pseudomonads (p less than 0.002), Enterobacteriaceae (p less than 0.001), and other aerobic Gram negatives (p less than 0.02). The enhanced performance increased to 53% if the patient was receiving any antibiotics at the time the blood was cultured. In patients known to be free of antibiotics at the time of blood draw, there was still an increased yield of 18%. The new system detected positivity at least one reading sooner than twice as often as the converse, and confirmed septic episodes significantly more often (21% overall) (41% on antibiotics) (15% no antibiotics). The BACTEC PLUS has distinct advantages over its low blood volume, nonresin counterpart. PMID- 1873970 TI - The outcome of candiduria in pediatric patients. AB - The presence of Candida in the urine of a seriously ill, pediatric patient presents a management problem because of a lack of information concerning the natural history of candiduria and its relationship to disseminated candidiasis. In this retrospective study, the outcome of candiduria was examined in a group of 54 pediatric patients to determine any predictors of disseminated candidiasis. Medical records were reviewed to identify urine collection methods, Candida colony counts, results of cultures from other body sites, antifungal therapy, and clinical course. Six (11%) of the 54 patients had evidence of systematic Candida infection. In only two of these patients was candiduria the first evidence of disseminated candidiasis. Invasive infection was associated with candiduria more frequently in neonates and patients with central venous catheters and/or immunosuppressive therapy. Urine colony counts were not helpful for assessing the risk of invasive disease. Candiduria appears to be of little consequence in patients who are generally healthy. However, candiduria in high-risk patients, even in the presence of perineal candidal infection or an indwelling urinary catheter, should prompt a careful evaluation for disseminated infection. PMID- 1873971 TI - A comparison of direct immunofluorescence, shell vial culture, and conventional cell culture for the rapid detection of influenza A and B. AB - Direct immunofluorescence (FA) and shell vial contrifugation cultures (SVCs) were compared with conventional tube cultures for the rapid detection of influenza A and B by using a commercial antibody. Of the 439 specimens tested, 82 were positive by conventional culture (CC). The direct smear prepared from pelleted cells or direct swab material exhibited positive fluorescence in only seven (8.5%) of these cases, whereas the SVC was positive in 30 (37%). The SVC method detected 12 additional positive isolates that were not recovered in CC. The mean time to isolation in CC was 3.6 days for influenza A and 4.3 days for influenza B. The use of SVC provided more rapid results (36-48 hr). The FA method, although more rapid, may be of limited sensitivity and difficult to interpret depending on the quality of the specimen. The results indicate that SVC complements conventional culture in the rapid detection of influenza and can detect infections that may be missed in conventional tubes, but should not be used to the exclusion of conventional culture. PMID- 1873972 TI - In vitro activity of an oxycephem OCP 9-176 compared with its sulfur analog and other beta-lactams. AB - OCP 9-176 is an oxycephem antibiotic that contains a 2-aminothiazolyl, carboxypropyl side chain at C-7 and a pyridinium thiomethyl group at C-3. OCP 9 176 was generally twofold less active than its sulfur-containing analog ME 1228 against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Providencia stuartii, Proteus vulgaris, and Serratia marcescens. Activity against Enterobacter cloacae and Citrobacter freundii was equivalent. OCP 9-176 was twofold less active than ME-1228 against Pseudomonas aeruginosa and Acinetobacter species. Activity of the two agents was similar against Staphylococcus aureus and Staphylococcus epidermidis. Although OCP 9-176 inhibited E. coli containing TEM-1 and TEM-2, it was less active than ME-1228. Klebsiella organisms with SHV-1 and K 2 beta-lactamases were inhibited, but TEM-3-containing isolates had MICs of 16 micrograms/ml. OCP 9-176 was minimally hydrolyzed by TEM-1, PSE-1, K-1, and P99, and it was a poor inhibitor of P99. Replacement of sulfur with oxygen does not increase the activity of compounds with sulfopyridinium methyl groups at C-3. PMID- 1873973 TI - Antibacterial activity of cefoperazone and cefoperazone plus sulbactam in a neutropenic site model. AB - Efficacy of cefoperazone versus cefoperazone plus sulbactam was studied in a rabbit neutropenic site infection model against a broad range of clinical isolates including six isolates each of staphylococci, enterococci, pneumococci, Enterobacteriaceae, and Pseudomonas aeruginosa. Therapy of cefoperazone plus sulbactam demonstrated enhanced efficacy against the staphylococci, pseudomonads, and Enterobacteriaceae. The activity of cefoperazone against enterococci and pneumococci was not enhanced or inhibited by the addition of sulbactam. Increased concentrations of cefoperazone found at the infection sites when sulbactam was added to the therapeutic regimen indicates that sulbactam provided a protection to cefoperazone from beta-lactamases produced by staphylococci and Enterobacteriaceae. The combination improved the efficacy of cefoperazone in this animal model. PMID- 1873974 TI - Effect of including recommendations for antimicrobial therapy in microbiology laboratory reports. AB - Innovative approaches are needed to improve cost-effective antibiotic use in hospitals. We established an algorithm to provide a recommendation for both a single oral and a single parenteral antimicrobic, including dosage, to be placed in the bacteriology laboratory report for therapy guidance of 174 episodes of lower respiratory infection in a group of "program" patients with no evidence of infection at other sites. The initial recommendation was based on the Gram stained direct smear of secretions. The recommendation was updated when preliminary culture results were available, and again with final identification and susceptibility data. We compared the severity of illness, length of stay, and cost of therapy for 68 episodes in program patients who received the recommended therapy with 111 episodes in a control group of patients who received antimicrobial therapy but for whom no recommendations were reported. There was a significantly greater use of the recommendations for sicker patients. Antimicrobial therapy, in general, was more often used for the program patients than for the controls. There was no difference in length of stay or therapy cost. We recommend that this approach be used in settings where there is more problematic use of antimicrobics. PMID- 1873975 TI - Infection of an arteriovenous fistula with Rothia dentocariosa. AB - Rothia dentocariosa is an unusual cause of infection in humans, despite the fact that the organism is frequently isolated from the oral cavity. The authors describe a case of R. dentocariosa infection following revision of an arteriovenous fistula in a 46-year-old diabetic man with renal failure. PMID- 1873976 TI - In vitro susceptibilities of Edwardsiella tarda to 22 antibiotics and antibiotic beta-lactamase-inhibitor agents. AB - The in vitro susceptibilities of 22 isolates of Edwardsiella tarda were studied with 22 antibiotics and antibiotic-beta-lactamase-inhibitor agents. Results indicated that all isolates were susceptible to the aminoglycosides, cephalosporins, penicillins, imipenem, aztreonam, ciprofloxacin, and antibiotic beta-lactamase-inhibitor agents. Each strain produced a beta-lactamase even though no resistance was detected to the beta-lactams. PMID- 1873977 TI - Comparison of blood-culture results after five and seven days of incubation using the BACTEC NR660. AB - We compared 16,606 blood cultures for microbial growth on days 5, 6, and 7 of incubation using the BACTEC NR660. Only 20 potentially significant organisms (0.8% of positive cultures) were detected after day 5 and only one resulted in a change of patient management. We recommend users of the BACTEC NR660 consider a 5 day protocol for routine blood cultures. PMID- 1873978 TI - Application of quadFERM+ for the identification of fastidious gram-positive and gram-negative bacilli. AB - The 2-hr quadFERM+ kit (qF) (Analytab Products, Plainview, NY) was compared with conventional tube tests for the identification of the HACEK bacteria (Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae), other Haemophilus and Kingella spp., Capnocytophaga, Corynbacterium, and Moraxella spp. Test results were identical for 296 comparisons with 74 isolates (74%). In the remaining 104 comparisons for 26 isolates, 50 reactions were identical, and qF produced a positive result in 46 of 54 discrepancies. PMID- 1873979 TI - Iron and heme contents of the extracellular hemoglobins and chlorocruorins of annelids. AB - 1. A survey of the literature on the extracellular hemoglobins and chlorocruorins of over 30 species of annelids, covering the last 30 years, shows that the range of iron content is 0.211-0.265 wt.% (mean = 0.228 +/- 0.013, N = 28) and the range of the heme content is 1.83-3.64 wt.% (mean = 2.60 +/- 0.38, N = 29). 2. There is relatively little scatter in the values of the experimental iron contents and only one of the 28 values is clearly outside the standard deviation range. 3. The values of heme contents are much more scattered, with seven values, clearly outside the standard deviation limits. 4. The aberrant cases are discussed and it is noted that the mean heme content of 2.60 wt.% corresponds to an iron content of 0.236 wt.% in excellent agreement with the mean iron content of 0.228 wt.%. 5. This result suggests strongly that experimental values of iron and heme contents outside the ranges of 0.211-0.243 and 2.3-2.7 wt.%, respectively, corresponding to a minimum molecular mass outside the range 23,000 26,000, should be regarded with caution. PMID- 1873980 TI - Lytic activity from schistosomes: interactions with blood cells. AB - 1. The schistosome lytic agent hemolyzed animal red blood cells (RBCs) containing high concentrations of membrane phosphatidyl choline (dog, mouse, and rat) more efficiently than RBCs having no phosphatidyl choline (goat and sheep). 2. Human mononuclear cells lost viability in the presence of the schistosome lytic agent. 3. Preincubating the lytic agent with phosphatidyl choline or bovine serum albumin reduced its lytic activity. 4. Extracellular albumin protected the RBCs from schistosome induced hemolysis. 5. Pretreatment of the RBCs with various proteases enhanced lysis by 10-30%. PMID- 1873981 TI - Biotin diffusion in stored chicken eggs: a re-assessment. AB - 1. The possibility that biotin in stored eggs migrates from the yolk into the albumen was re-investigated. 2. Sets of eggs collected from 12 Single Comb White Leghorn hens were stored at 5, 8, 12, 15, or 18 degrees C for 5, 10, 15, 20, or 25 days and then frozen. 3. For each set, yolk and albumen samples adjacent to the yolk membrane were each pooled and assayed for protein-bound biotin by radioligand exchange with non-linear regression analysis of the data. 4. In contrast to previous work reported by Bush and White (Comp. Biochem. Physiol. 93B, 543-547, 1989), no evidence of biotin diffusion was found. 5. Non-linear regression was used to re-evaluate the data from the earlier study, confirming the results, although less strikingly. 6. The discrepancy is partly due to the method of data analysis, although differences in breed or number of hens may also be contributing factors. PMID- 1873982 TI - Hemoglobin biosynthesis enhancement following mitochondrial membrane growth and differentiation. AB - 1. A quantitative increase of organelles in early reticulocytes has been observed compared to that found in late erythroblasts of the peripheral rabbit embryo blood. 2. The increase is due to the formation of hemosomes, organelles taken as sites for final hemoglobin (Hb) biosynthesis or where the assembly of heme and globin polypeptides could occur. 3. These organelles derive indirectly from mitochondria whose internal membrane grows concomitantly to its differentiation, originating lamellated bodies that modify successively to prehemosomal vesicles, prohemosomes and hemosomes. 4. The occurrence of membrane synthesis for the formation of lamellated bodies could explain the increase of organelles per cell and, thereby, the enhancement of the Hb biosynthesis rate in peripheral embryo blood in relation to this biosynthesis rate in the liver, as had been biochemically ascertained by other authors. PMID- 1873983 TI - Subunit structure of the hemocyanins of some of the Muricidae and Fasciolariidae families: Chicoreus florifer dilectus (A. Adams), Muricanthus fulvescens (Sowerby), Urosalpinx cinerea (Say), Fascilaria lilium hunteria (Perry), and Pleuroploca gigantea (Kiener). AB - 1. The hemocyanins of the Muricidae and Fasciolariidae families of marine gastropods: Chicoreus florifer dilectus, Muricanthus fulvescens, Urosalpinx cinerea, Fasciolaria lilium hunteria, and Pleuroploca gigantea were investigated by sedimentation velocity, scanning transmission electron microscopy, light scattering, and other physical techniques. 2. The hemocyanins of these species are characterized by sedimentation coefficients close to 100 S and molecular weights of 8.2 x 10(6)-9.0 x 10(6). 3. The hemocyanins have di-decameric structures, with tail-to-tail arrangement of the decameric halves of the cylindrical particles. Only the hemocyanin of U. cinerea was found to contain about 30% higher, tri-, and tetra-decameric particles, with one or two decameric units added in a tail-to-head manner to a central di-decameric particle of the Mellema and Klug tail-to-tail arrangement. 4. The influence of pH, and the urea and Hofmeister salt series of reagents on the subunit structure and denaturation of P. gigantea hemocyanin were also investigated. PMID- 1873984 TI - Changes in testicular lactate dehydrogenases of the rat (Rattus norvegicus) during growth and development. AB - 1. We have quantified lactate dehydrogenase (LDH) A, B and C enzyme levels during the first twelve weeks of life in rat testes. 2. Proteins were electrophoresed under non-denaturing conditions, isoenzymes identified by activity staining and quantified by densitometry scanning. 3. LDH A declined 2-3-fold during testes growth, changing from the most to the least abundant isoenzyme form. LDH B remained fairly constant, and LDH C increased from undetectable levels at birth to become the most abundant of the three polypeptides from week 3 onwards. PMID- 1873985 TI - Effect of lactation on gluconeogenesis and ketogenesis in ovine hepatocytes. AB - 1. Rates of glucose synthesis from radioactive precursors and ketogenesis were determined in hepatocytes from control and lactating sheep. 2. Gluconeogenesis from propionate was the same in both groups. Gluconeogenesis from lactate + pyruvate was three-fold higher in hepatocytes from lactating sheep. Palmitate stimulated gluconeogenesis from lactate + pyruvate in both groups. 3. Rates of ketogenesis from palmitate but not butyrate were slightly higher in hepatocytes from lactating sheep. No other differences in the metabolism of palmitate or butyrate were seen in the two groups. Exogenous carnitine stimulated ketogenesis from palmitate. Propionate inhibited ketogenesis from palmitate and butyrate. Lactate + pyruvate also inhibited ketogenesis slightly but stimulated oxidation and esterification. 4. It is concluded that the major changes in glucose and ketone production seen in the lactating ruminant are not the result of long-term changes within the hepatocyte but occur because of the changes in substrate supply to the liver and changes in intracellular concentrations of metabolites. PMID- 1873986 TI - Each otoconia polymorph has a protein unique to that polymorph. AB - 1. Otoconia, contained within the vestibular portion of the inner ear, are mineralized by one of three polymorphs of calcium carbonate. Each otoconial polymorph contains a unique, major protein. 2. The major protein of calcitic otoconia of members of different vertebrate classes, Amphibia (African clawed frog) and Mammalia (rat), have similar molecular weights. 3. The major protein of calcitic rat otoconia and of vateritic otoconia of the gar may be calcium binding proteins. No protein from the other polymorph, aragonite, appear to have this characteristic. PMID- 1873987 TI - Comparative biochemistry of mammalian arylsulfatase C and steroid sulfatase. AB - 1. Hepatic arylsulfatase C (ASC) and steroid sulfatase (SS) from six of eleven mammals (rat, dog, baboon, cow, goat, and sheep) coeluted from DEAE-Sephacel as a single anionic species. A minor cationic peak of ASC and SS activity was also recovered from solubilized microsomes derived from the domestic cat. Characterization of the cationic activities indicated they were most likely contributed by a protein structurally related to the anionic isozyme. Properties of ASC and SS activities occurring in these seven species were most consistent with the presence of both activities in the same enzyme. 2. Guinea-pig liver SS activity was partitioned between an alkylsulfatase (hydrolyzing dehydroepiandrosterone sulfate (DHEAS)) and an arylsulfatase (hydrolyzing both estrone sulfate (E1S) and 4-methylumbelliferyl sulfate (4MUS) at a common active site). These enzymes were physically separable by ion-exchange chromatography and possessed distinct immunological and chemical properties. 3. Porcine, squirrel, and human livers possessed a major isozyme of ASC that lacked both E1S- and DHEAS sulfatase activities. The human hepatic ASC was separable from SS by electrophoresis and was partially resolved from SS by DEAE-Sephacel chromatography. The ASC isozyme lacking SS activity was heat-labile in all three species. PMID- 1873988 TI - Kinetics of the reduction of oxaloacetate catalyzed by mitochondrial malate dehydrogenase of Toxocara canis muscle. AB - 1. The reaction of reduction of oxaloacetate to L-malate in the presence of NADH catalyzed by mitochondrial malate dehydrogenase (EC 1.1.1.37) of Toxocara canis muscle has been studied. 2. The data obtained in initial velocity experiments as well as those involving product inhibition suggest that the reaction mechanism is of the sequential type with a kinetically significant ternary complex and in which the coenzymes bind to the free enzyme. 3. The kinetic parameters, including the inhibition constant for NADH were estimated by non-linear regression analysis using the appropriate rate equations. PMID- 1873989 TI - Antibodies to ovine adipocyte plasma membranes recognize tissue and species specific plasma membrane components. AB - 1. Ovine adipocyte plasma membrane (PM) contains three unique proteins that have relative molecular mass of 70, 106, and 110 kD which are lacking in PM from liver, kidney, heart, and red blood cells. 2. Two major proteins on ovine adipocyte PM having molecular mass of 44 and 46 kD which were also present on porcine adipocyte PM. 3. These ovine proteins could not be detected on either rat or chicken adipocyte PM. PMID- 1873990 TI - The carotenoids of wild and blue disease affected farmed tiger shrimp (Penaeus monodon, Fabricus). AB - 1. The main carotenoids in wild Penaeus monodon exoskeleton were astaxanthin di- and mono-esters, astaxanthin, and beta-carotene. 2. Wild P. monodon exoskeleton contained on average 26.3 ppm total carotenoid; normally pigmented farmed shrimp had a similar concentration (25.3 ppm). 3. Exoskeletons of farmed "blue" P. monodon (i.e. blue-coloured, as opposed to the normally red-blue/black banded shrimp) contained significantly less total carotenoid (4.3-7 ppm). The only major carotenoid being astaxanthin. 4. Commercially available diets contained only trace quantities of canthaxanthin. 5. Nutritional deficiency with respect to carotenoids is suggested as the cause of blue disease in farmed P. monodon. PMID- 1873991 TI - A pharmacodynamic approach to optimizing insulin therapy. AB - We have developed a program for simulation and optimization of insulin therapy in patients with insulin-dependent diabetes. The program, denoted GLUCOJECT, is based on a physiologic model of minimal complexity, which describes the pharmacokinetics of absorption and clearance of subcutaneous insulin and the dynamics of glucose utilization as dependent on both prevailing glucose and insulin levels. With self-monitored glucose values and insulin doses collected with one of several commercially available memory meters, GLUCOJECT reconstructs an average or 'typical' daily plasma glucose and insulin profile and displays them in a graph. The program then calculates the expected rate of glucose utilization, which permits calculation of the rate of glucose entry into plasma from both endogenous (hepatic) and exogenous (dietary) sources. In turn, this allows one to calculate an 'ideal' plasma insulin profile required to maintain a relatively constant 'ideal' plasma glucose level. GLUCOJECT can evaluate several different insulin regimens involving various combinations of short-, intermediate and long-acting insulins, and select the one(s) most closely approximating the ideal or optimal insulin profile, using a least-squares criterion. For any optimized insulin regimen, GLUCOJECT calculates and displays the predicted time course of plasma glucose. These features make the program attractive as an educational tool for both patients and health care professionals and could potentially assist in the management of patients with insulin-dependent diabetes. PMID- 1873992 TI - Software for estimating LD50 and LD90 by logit analysis. AB - We describe a user-friendly software package using Turbo Pascal language under MS DOS environment for estimating LD50 and LD90 by Logit Analysis with a X2 test of goodness of fit for the model. PMID- 1873993 TI - A computer management system for patient simulations. AB - A series of interactive videodisc patient simulations is being used to teach clinical problem-solving skills, including diagnosis and management, to dental students. This series is called Oral Disease Simulations for Diagnosis and Management (ODSDM). A computer management system has been developed in response to the following needs. First, the sequence in which students perform simulations is critical. Second, maintaining records of completed simulations and student performance on each simulation is a time-consuming task for faculty. Third, the simulations require ongoing evaluation to ensure high quality instruction. The primary objective of the management system is to ensure that each student masters diagnosis. Mastery must be obtained at a specific level before advancing to the next level. The management system does this by individualizing the sequence of the simulations to adapt to the needs of each student. The management system generates reports which provide information about students or the simulations. Student reports contain demographic and performance information. System reports include information about individual patient simulations and act as a quality control mechanism for the simulations. PMID- 1873994 TI - Fluxplus, a microcomputer program for interactive calculation of 'in vitro' solute fluxes, uptakes and accumulations in studies of intestinal transport. AB - A new microcomputer program for interactive comparisons, analysis and calculation of in vitro solute transepithelial fluxes and nutrient uptakes and accumulations by intestinal tissues is described. The program is written in Microsoft GWBASIC for the widely distributed IBM-PC. Flux, uptake and accumulation values are obtained by computation from initial sequential data files and stored in sequential or random-orgaized files, depending on the specific process. Computed unidirectional fluxes are saved together with their associate electrical variables. The program calculates univariate statistics for unidirectional and net fluxes, and allows comparisons between selected groups of experiments by using the Student's t-test. An homocedasticity test is also provided. Active uptake or accumulations of solutes are calculated by substracting the predicted diffusive values at a determined concentration to total uptake or accumulation and from this, kinetic parameters are computed. The program was designed to be user-friendly and includes several functions to permit the user to manage and examine stored data. Examples of outputs illustrate applications of the program. PMID- 1873995 TI - Cubic regression analysis for radioimmunoassay data processing. PMID- 1873996 TI - A method for the correction of drift in movement analysis. AB - A method is proposed for the correction of drift over cyclic three-dimensional kinematic data during treadmill locomotion. An adaptive least-squares drift correction algorithm (ALSDC) is developed from the operational definition of no drift. This method includes automatic selection of least-squares polynomial degree and sequential processing of large data sets. PMID- 1873997 TI - Analysis of multiple-choice items. AB - This paper deals with scoring and analysis of multiple-choice exam questions. Data may be read by an optical mark reader scanner or from a file created by a system editor and stored in a format convenient to be analysed by a specially designed program 'MCQ'. In addition the data file created can be linked with the package SPSSx for pertinent statistical methods or SPSS Graphics for illustration of score and item distributions. The MCQ program comprises: (1) scoring; (2) item analysis: difficulty and discrimination indices; (3) testing the goodness of alternatives attached to each question. The method is applicable to multiple choice questions with 4.5 greater than 5; true/false and combined exam questions. The method should prove useful for instructors to build up a balanced discriminant questions bank. PMID- 1873998 TI - Comparison of two nonlinear models for fitting saccadic eye movement data. AB - Saccadic eye movements are rapid shifts in the direction of gaze which are being studied increasingly for clinical and pharmacological purposes. The evaluation of the relationship between amplitude and peak velocity of these ocular movements (the so-called 'main sequence' plot) is particularly useful for characterising the saccade pattern in individual patients. This relationship is nonlinear and the peak velocity tends to achieve an asymptote for high values of amplitude. Since a standard parametrisation of the main sequence based on specific mathematical models has not yet been achieved, in the present study two simple models based on the Michaelis-Menten equation and on an exponential equation are proposed together with their implementation on a microcomputer. Two microcomputer programs are described which estimate the model parameters from the experimental data of the patients using a weighted nonlinear least-squares fit. The two procedures have been tested and compared in a series of 23 healthy volunteers. The following results (mean +/- S.D.) were obtained: Michaelis-Menten model. Km (degrees) = 31.2 +/- 7.7, Vmax (degrees/s) = 841.0 +/- 165.5, root-mean-squared error(%) = 6.0 +/- 1.6; exponential model. K (degrees) = 23.4 +/- 4.6, Vmax (degrees/s) = 578.0 +/- 97.4, root-mean-squared error(%) = 5.4 +/- 1.6. The two techniques of parametrisation provided similar indices of intra-individual variability in 4 healthy volunteers. In conclusion, our methods for saccade parametrisation can be regarded as simple but efficient tools for facilitating research on these ocular movements. PMID- 1873999 TI - The glucoamylase multigene family in Saccharomyces cerevisiae var. diastaticus: an overview. AB - Saccharomyces cerevisiae has been used widely both as a model system for unraveling the biochemical, genetic, and molecular details of gene expression and the secretion process, and as a host for the production of heterologous proteins of biotechnological interest. The potential of starch as a renewable biological resource has stimulated research into amylolytic enzymes and the broadening of the substrate range of S. cerevisiae. The enzymatic hydrolysis of starch, consisting of linear (amylose) and branched glucose polymers (amylopectin), is catalyzed by alpha- and beta-amylases, glucoamylases, and debranching enzymes, e.g., pullulanases. Starch utilization in the yeast S. cerevisiae var. diastaticus depends on the expression of the three unlinked genes, STA1 (chr. IV), STA2 (chr. II), and STA3 (chr. XIV), each encoding one of the extracellular glycosylated glucoamylases isozymes GAI, GAII, or GAIII, respectively. The restriction endonuclease maps of STA1, STA2, and STA3 are identical. These genes are absent in S. cerevisiae, but a related gene, SGA1, encoding an intracellular, sporulation-specific glucoamylase (SGA), is present. SGA1 is homologous to the middle and 3' regions of the STA genes, but lacks a 5' sequence that encodes the domain for secretion of the extracellular glucoamylases. The STA genes are positively regulated by the presence of three GAM genes. In addition to positive regulation, the STA genes are regulated negatively at three levels. Whereas strains of S. diastaticus are capable of expressing the STA genes, most strains of S. cerevisiae contain STA10, whose presence represses the expression of the STA genes in an undefined manner. The STA genes are also repressed in diploid cells, presumably by the MATa/MAT alpha-encoded repressor. STA gene expression is reduced in liquid synthetic media, it is carbon catabolite repressed by glucose, and is inhibited in petite mutants. PMID- 1874000 TI - Comparative modeling of proteins in the design of novel renin inhibitors. AB - Renin, the first enzyme in the renin-angiotensin system, is critically important for the maintenance of blood pressure, and, therefore, as a target for antihypertensive therapy. The three-dimensional structure of renin would be an invaluable aid in understanding the functional properties of renin as well as in the design of novel, potent inhibitors. Three-dimensional models of renin have been developed by a number of different groups based on comparative homology modeling from the other known aspartic proteinase structures. These models have been used widely in the drug design process to suggest targets for synthesis and to rationalize the structure-activity relationships of compounds. This review describes the different published renin models and compares them to the extent possible. Applications of these model renin and renin-inhibitor complex structures to biological function and inhibitor design are summarized. PMID- 1874001 TI - The state construction of affect: political ethos and mental health among Salvadoran refugees. AB - This essay seeks to extend current anthropological theorizing on emotion. Although anthropologists have convincingly established the specifically cultural status of emotion, recognition also of "state" (including sociopolitical institutions of nation-states) constructions of affect has been slow in coming. The present essay seeks to expand the emerging scholarly discourse on the emotions by examining the nexus among the role of the state in constructing a political ethos, the personal emotions of those who dwell in that ethos, and the mental health consequences for refugees. This analysis is intended as a bridge between analyses of the state construction of affect, on the one hand, and the phenomenology of those affects, on the other. To illustrate, I examine the state construction of affect and its traces in the narrative and clinical presentations of Salvadoran refugees in North America. The saliency of fear and anxiety among a group of psychiatric out-patients is framed by bodily experience, knowledge of illness, and the ethnopsychology of emotion within the context of chronic political violence and poverty. Distinctions between terror and torture, distress and disease are proposed as essential to an account of refugee experience. Future directions for the study of the "state construction of affect" are suggested. PMID- 1874002 TI - Emotional distress and its socio-political correlates in Salvadoran refugees: analysis of a clinical sample. AB - The emotional distress responses of refugees cannot be adequately understood using the traditional notions of stress and adaptation. In these populations it is necessary to consider the relations between emotional distress and socio political context, particularly the processes of terror and intimidation and the conditions of migratory illegality and social marginality. This study analyses the patterns of emotional distress in a clinical sample of 71 Salvadoran refugees in an urban center of the United States. Case histories are presented and patterns of trauma, distress and associated life problems analyzed. It is argued that distress patterns reflect the particular socio-political conditions of women and men and represent the embodiment of the conflicts that refugees face. The concept of illness is used to link distress patterns and socio-political context and to avoid the reductionism of psychiatric categories. PMID- 1874003 TI - Psychiatric care in relation to the development of the contemporary state: the case of Catalonia. AB - Over the past two centuries, extensive mental health care systems have come to be a feature of all Western societies. However, the theoretical model generally invoked to account for this process has only limited applicability to Spain, where the growth of capitalism and the liberal state followed an atypical and uneven course. Political power and economic power, usually coterminous, were divided in Spain between center and periphery, so that, until the 1960s, Spain's economic center of gravity was localized in Catalonia, the most culturally and linguistically distinct region. Here we are dealing with a paradox: on the one hand, the failure of the incompletely centralized and economically underdeveloped Spanish state to develop a system of psychiatric care comparable to those of other European states; and on the other hand, the success of the Catalan bourgeoise, though lacking a state of its own, in creating such a system through private initiative. PMID- 1874004 TI - The politics of black patients' identity: ward-rounds on the 'black side' of a South African psychiatric hospital. AB - There are many macrosocial studies of the political organisation of health and mental health care in South Africa, and the maldistribution of resources by race is well known. Little attention, however, has been given to the minutiae of the negotiation of power in the clinical setting. This article, which reports on part of a larger study of aspects of culture in South African psychiatry, focuses on interactions in ward-rounds on the 'Black side' of a South African psychiatric hospital. Through analysis of cases, the complexity of interpreting what transpires in such a setting and the central role that the concept of culture has in debates amongst staff members are demonstrated. Close analysis demonstrates the inadequacy of models which seek to locate the institutional racism of apartheid psychiatry in the motives of individual clinicians. Clinicians may simultaneously reproduce and subvert aspects of apartheid practice. A consideration of the social positioning of the clinician both as a South African and as a practitioner of psychiatry is central to the development of psychiatry in a post-apartheid South Africa. PMID- 1874005 TI - Invisibility and selective avoidance: gender and ethnicity in psychiatry and psychiatric nursing staff interaction. AB - This research-based article analyzes institutionalized inequity and discrimination in the forms of sexism and racism within a large, busy, contemporary medical center's Department of Psychiatry. Within that context, issues of control and mechanisms of avoidance served to perpetuate contradictions inherent in what professes to be a psychologically therapeutic and empowering milieu. Despite cognizance of the roles that culture and gender play in care and treatment of patients, psychiatric and mental health professionals at "Central" tended to avoid critical examination of their own and co-workers' ethnicity and gender as those characteristics influenced life experiences, occupational roles and statuses, and hierarchical relationships. PMID- 1874006 TI - Medical management of early-stage breast cancer. AB - With improved screening and education, a greater proportion of breast cancer is detected at an early stage. Although the prognosis for many of these patients is excellent following definitive local therapy alone, some subsets of node-negative patients have a 30% chance of eventually developing metastatic disease that will be incurable with current therapy. Thus, an increasing proportion of early-stage patients are being offered some form of adjuvant therapy, with the expectation of improved relapse-free survival, and possibly improved overall survival. Efforts have been made to base the selection of patients for adjuvant therapy on specific prognostic factors. Meanwhile, the scope and complexity of putative prognostic factors continues to widen, and now includes such items as the presence of occult microscopic metastases, DNA ploidy and proliferative fraction, cytogenetic abnormalities, oncogene expression, growth factor receptors, and expression of hormonally regulated proteins. In addition, there is now a considerable range of options with regard to the composition, dose intensity, and sequence of multimodality therapy. Data regarding the classification, significance, and interpretation of prognostic factors is reviewed together with the development, current status, and recommendations regarding adjuvant therapy for patients with early-stage breast cancer. For 1991, the National Cancer Institute (NCI) has estimated that 175,000 new cases of breast cancer will be diagnosed in American women. It is also estimated that 44,500 women will die of breast cancer. Unfortunately, the age-adjusted death rate from breast cancer has shown no overall change from 1930 through 1987. However, effective screening techniques continue to identify an increasing percentage of early-stage tumors, which should exceed 50% of all new tumors in 1991. Ultimately, our understanding of environmental and genetic risk factors may identify new ways to reduce the impact of this disease. In the interim, development and application of effective systemic adjuvant chemotherapy and hormonal therapy has become increasingly important. There is no question that a greater proportion of patients with less extensive disease are now being offered some form of adjuvant therapy. Meanwhile, selection of patients for adjuvant therapy, and choice among specific adjuvant regimens, has remained controversial. Analysis of multiple prognostic factors is performed not only in the context of cooperative investigational trials, but more often in the offices of individual physicians caring for individual patients. Tumor biopsies can now be routinely sent to specialized laboratories for performance of complex assays with potential prognostic information, although interpretation of these results with reference to a specific patient is often uncertain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1874007 TI - Parietal cell vagotomy and selective vagotomy plus antrectomy in the treatment of duodenal ulcer. A follow-up of 10 years. AB - Two hundred and thirty-eight patients with duodenal ulcer were subjected to vagotomy. According to the clinical manifestations and the results of gastric acid secretion test, parietal cell vagotomy was done in 100 patients and selective vagotomy plus antrectomy in 138 patients. Follow-up after operation for 10 years showed that 96% and 97% of patients belonged to Visick Grade I and II respectively. The recurrence rate for parietal cell vagotomy was 1.96%, but no recurrence was seen in the group of selective vagotomy plus antrectomy. Long-term side-effects were rarely found in the patients. They had good nutritional states. The follow-up data showed that the recurrence rate could be greatly reduced if the modality of vagotomy was selected according to the type of gastric acid secretion test. The importance of surgeons experience and careful manipulation was emphasized. PMID- 1874008 TI - A preliminary study of radioimmunoimaging by 131I-COC183B2 monoclonal antibody in patients with epithelial ovarian cancer. AB - Monoclonal antibody 131I-COC183B2, developed in our laboratory and proved to fit for human treatment was injected intraperitoneally or subcutaneously in 13 patients. In 8 cases with i.p. injection the disease corresponded with the image, i.e. 3 primary ovarian epithelial cancers showed positive images, 1 ovarian Krukenberg tumor was negative and the other 4 negative images included 1 uterine myoma and 3 ovarian teratomas. In the subcutaneous injection group, 4 cases had ovarian carcinoma, surgery and chemotherapy. Two negative images corresponded with the clinical status-in good health, another negative case had metastatic left supraclavicular lymph node due to ovarian mucinous adenocarcinoma. The last negative image in this group was a case of benign ovarian teratoma which was proved after surgery. The 1 positive case was waiting to be proved by a scheduled third operation. The computer scintigram calculation of T/NT was 5.35 to 13.7. The results suggest that this monoclonal antibody can be used for radioimmunoimaging for the localization of ovarian carcinoma, which is not only helpful for clinical staging and differential diagnosis but is also a good follow up method. PMID- 1874009 TI - Four-year experience in the treatment of upper gastrointestinal strictures with balloon dilatation. AB - One hundred and sixty-four cases of upper gastrointestinal tract stricture were treated by balloon dilatation in 4 years. A total of 682 procedures were performed. One hundred and forty cases (anastomosis stenosis 95, caustic stenosis 33 and other stenoses of the esophagus 12) were followed up with an effective rate of 90% (126/140) and a long-term effective rate of 71.4% (100/140). Fourteen cases (10%) failed, and 11 of them were due to tumor recurrence. The concept about the short-term and long-term effects, the criteria for evaluation of the results, the factors influencing the effectiveness, and the time suitable for dilatation are described. For the dilatation, indications are anastomosis stricture of the upper gastrointestinal tract, esophageal web and caustic stenosis of the esophagus. This method is also indicated for cicatricial stricture of the upper gastrointestinal tract of various causes. PMID- 1874010 TI - Immunoglobulin G subclass deficiency in children with recurrent respiratory tract infections. AB - With monoclonal antibodies serum immunoglobulin G(IgG) subclasses were measured in seventy children aged 2 to 13 years with recurrent respiratory tract infections including upper respiratory tract infections, otitis media, sinusitis, asthmatic bronchitis and pneumonia. 211 healthy, aged-matched children served as control. IgG subclass deficiency was found in 19 out of the 70 patients (27.1%, single IgG1 deficiency in 7, IgG2 deficiency in 4, combined IgG1-IgG3 deficiency in 5, IgG1-IgG2-IgG3-IgG4 deficiency, IgG1-IgG2-IgG4 deficiency and IgG2-IgG4 deficiency each in 1). The incidence of IgG subclass deficiencies was in the sequence as follows: IgG1, 20%; IgG2, 10%; IgG3, 8.6% and IgG4, 4.3%. The results suggest that IgG subclass deficiency indicate a common disorder in children with recurrent respiratory tract infections. PMID- 1874011 TI - Significance of pre-S2 protein and its antibody in children with HBV infections. AB - Pre-S2 protein and its antibody were detected in 130 children with hepatitis B virus (HBV) infection and 30 with T6 hepatitis B (HB) vaccination. The results showed that pre-S2 was positive in most chronic persistent hepatitis (CPH) and chronic active hepatitis(CAH) patients, while anti-pre-S2 was positive in only 8% (2/92 cases) and 11.5% (3/26 cases) respectively. The positive rate of anti-pre S2 was 78.9% (15/19 cases) in cases at the convalescent stage of acute hepatitis B, 91.7% (55/60 cases) in cases with T6 HB vaccination and 83.3% (25.30 cases) in naturally acquired anti-HBs children, while pre-S2 was not noted. Anti-pre-S2 was negatively related to ALT and positively to anti-HBs (P less than 0.01). The positive relation of pre-S2 to HBsAg was observed. These results suggest that pre S2 could be a marker for HBV infection, and anti-pre-S2 may indicate a favourable prognosis of HBV infection. There was no correlation between anti-pre-S2 and pathogenic damages induced by HBV. PMID- 1874012 TI - Electronic monitoring of fetal heart rate and determination of fetal scalp blood pH in prediction of intrapartum fetal distress. AB - A prospective study on consecutive fetal monitoring in 559 deliveries was carried out. The difference between the first 30-minute and the last 30-minute monitoring was compared. Abnormal fetal heart rate (FHR) pattern in the last 30 minutes combined with abnormal fetal scalp blood pH has a good predictability of 1- and 5 minute Apgar scores. The correlation of fetal heart rate-uterine contraction (FHR UC) monitoring (525 cases) and fetal scalp blood pH determinations (FSB-pH) (79 cases) with the fetal condition was assessed. It is indicated that the first 30 minute FHR tracing can reflect the fetal status in labor, and FHR-UC monitoring assessment is evidently superior to FSB-pH in the prediction of a vigorous fetus. Whereas, FSB-pH is superior to FHR-UC monitoring in the prediction of a compromised fetus. PMID- 1874013 TI - Angiographic prediction of cardiac events after first acute transmural myocardial infarction. A prospective study of 108 patients. AB - 108 patients with acute myocardial infarction (MI), aged 70 years or younger, underwent left ventriculography and coronary arteriography (mean one month) after infarction and were followed up for an average period of 22 months (range 5-47 months). The contribution of angiographic variables to a first cardiac event (death, recurrent infarction, coronary artery bypass grafting or congestive heart failure) was evaluated with Kaplan-Meier survival curve analysis and long-rank test. Patients with cardiac events had left ventricular dilation, systolic dysfunction, multivessel coronary disease and lack of residual flow to the infarct region. Multivariate analysis showed that left ventricular end-systolic volume (P less than 0.001), end-diastolic volume (P less than 0.01) and the number of the diseased coronary vessels (P less than 0.05) were of significance in predicting the outcome. This prospective study indicates that in survivors of first acute transmural MI, cardiac catheterization performed one month after infarction can provide additive prognostic information that can be used to stratify risk. PMID- 1874014 TI - Second meiotic division of Plasmodium vivax. AB - During the formation of sporozoites, the nuclei formed after mitotic division in sporoblast enter sporozoite buds. The spindle appears in the nucleus of the sporozoite bud, while its nuclear membrane disappears. The spindle is an evidence of the second meiosis of the life cycle of plasmodium. PMID- 1874015 TI - Recent studies on antimalarial efficacy of piperaquine and hydroxypiperaquine. AB - Piperaquine and hydroxypiperaquine seem to be successful candidates of antimalarial drugs in China. Their antimalarial efficacy, experimental resistance, combination, mode of antimalarial action and clinical trials are described briefly. PMID- 1874016 TI - Soft tissue expansion in the treatment of scar alopecia in preschool children. AB - Indigenous rubber silicon gel soft tissue expanders were used to treat 5 preschool children with scar alopecia. The scar resection rate wa 100%; no severe complication happened. The average healing time was 25 days after the improvement of technical method. This method is simple, effective and the expansion duration is short. PMID- 1874017 TI - Fever, shortness of breath and shadow in the lung. PMID- 1874018 TI - Reassessment on roentgenologic signs of early rickets. Roentgenopathologic correlations of 52 en block specimens. AB - Correlation of the X-ray manifestation and the en bloc sections of 52 wrists of infants and children aged from 0-4 years from autopsy was carried out to identify the real X-ray signs of rickets. Simple ill-defined provisional calcified zone (PCZ), enlargement of head of ulna, shallow saucer-shaped and undulant or multilaminar PCZ are normal in variation. The signs of early rickets included marginal spur, saucer-shaped deformity, ill-defined and disordered trabeculae under PCZ, mild brush appearance and osteoporosis. However, only when five of the above mentioned criteria were met at the same time, can early rickets be diagnosed. PMID- 1874019 TI - Digital replantation. A ten-year retrospective study. AB - Eight hundred and two digits (592 complete amputation and 210 incomplete amputations) of 549 patients were replanted. The male to female ratio was 3:1 and the age range 1-63 years. 728 digits survived and 74 digits failed. The overall survival rate was 90.8%. Special varieties of complicated amputation were encountered in this series: (1) distal segment replantation, 139 digits, 131 digits (94%) survived; (2) digital replantation of children, 45 cases, 78 digits, average age 3.8 years, the youngest being 1 year old, 68 digits survived (88.7%); (3) rotational avulsion amputation of thumb, 26 digits, 23 digits (88.4%) survived; (4) bilateral digit amputation, 8 cases, 44 digits amputated, 38 digits replanted, including 9 digits of a ten-digit guillotined case. All the digits were salvaged. We conclude that thorough debridement, meticulous anastomosis of blood vessels and timely management of vascular crisis are keys to high survival rate, while judicious selection of indication, proper internal fixation of bone, anastomosis of as many blood vessels as possible, attentive repair of nerves and tendons, sound rehabilitation program are important measures in improving postoperative function. PMID- 1874020 TI - Major achievements and experience in filariasis control in the People's Republic of China. National Technical Steering Group for Filariasis Control and Research. AB - Filariasis control including a preparatory phase in the early 50s and two more extensive campaigns in the late 50s and 70s, has gained remarkable achievements. By the end of 1987, filariasis in 781 (90.4%) of 864 counties/cities was brought under control, i.e., the microfilariasis rate declined to less than 1% in the whole population in every village concerned. At present, there remain about 2,446,000 filariasis cases, accounting for 7.9% of 30,099,400 before nationwide campaigns. Microfilaria carriers among the remaining cases amounted to 1,473,000 and amicrofilaremic but symptomatic, to 973,000. The major experience comprises the integration of the control project into national health program, the mobilization of various sectors, including the community, the investigators and technical personnel in research institutions and control services all to participate and cooperate in problems and difficulties encountered. PMID- 1874021 TI - Quantification of circulating schistosome antigen by monoclonal antibody-based enzyme-linked immunosorbent assay. AB - A two-site enzyme-linked immunosorbent assay (2S-ELISA) was developed for the quantification of gut-associated schistosome circulating anodic proteoglycan (GASCAP) of Schistosoma japonicum using a monoclonal antibody (McAb M120), purified by one-step hydroxylapatite (HAP) chromatography, as both solid phase and peroxidase-conjugated reagent. In this system, a high detectable level of serum GASCAP concentration (0.25 microgram/L) could be achieved with the immunoaffinity purified GASCAP being used as the standard. The specificity of the assay was 97.2%, with minimized interference of rheumatoid factor. The intra assay (4.01%) and interassay (6.09%) coefficients of variation and the mean analytical recovery (101.4%) for GASCAP demonstrated the precision and accuracy of the assay. PMID- 1874022 TI - Subtypes of intestinal metaplasia and gastric carcinoma. A clinicoendoscopic follow-up of 112 cases. AB - Nine tumor-associated antigens (MG7-, MGdl-, MC3-corresponding antigens, CEA, P21ras, Sialoglycoprotein, CA 19-9-like, Sialo-Tn and Le8-like antigens) were investigated on biopsy specimens of different types of intestinal metaplasia (types I, II and III) taken from 112 patients with benign gastric conditions. The incidence of positive staining for 9 antigens except for P21ras in type III intestinal metaplasia was significantly higher than that in types I and II (P less than 0.05-0.01). These 112 patients were clinicoendoscopically followed up for 15-70 months. Five of them were found to develop gastric carcinomas within 25 60 months, giving a cancer detection rate of 4.5%. They were detected from type III (16.1%) patients, but none was found in patients of types I and II, and the differences were significant (P less than 0.05-0.01). Our results indicate that type III intestinal metaplasia has a higher potentiality in developing malignancy and that MG7, MGd1, MC3, CEA, CA19-9-like and Sialo-Tn antigens are valuable tumor markers in defining the high-risk group of gastric carcinoma. PMID- 1874023 TI - Application of pyridostigmine in evaluation of growth hormone reserves in children and adolescents. AB - There is evidence that the cholinergic system positively modulates growth hormone (GH) secretion. In the present study, we observed the effects of cholinergic enhancement by pyridostigmine (PD), a cholinesterases inhibitor, on GH release in both normal (n = 13) and GH deficient children and adolescents (n = 10). Responses of GH to insulin hypoglycemia (Ins) were also observed. In the normal subjects, PD-induced serum GH peak level was significantly higher than that induced by Ins (P less than 0.01), while the GH level in the patients with pituitary dwarfism showed no increase in both tests. This study indicates that PD test may be considered a sensitive dynamic test in evaluating pituitary function of GH secretion in children and adolescents. PMID- 1874024 TI - Homotransplantation of adrenal gland. AB - Eight patients with Addison's disease or Cushing's syndrome received adrenal homograft for 9 times after total adrenalectomy. All patients were followed up for 1 to 5 years. Symptoms and signs were improved without the supplement of steroids. The grafts showed satisfactory endocrinal functions in the recipients, but the grafts were dead in two patients 2 and 4 years after operation respectively. One of the two patients received the second homograft with good result. Single perfusion and ice-storage method of the all-adrenal gland and their clinical results were also presented. PMID- 1874025 TI - Balloon dilation treatment of phimosis in boys. Report of 512 cases. AB - Five hundred and twelve boys, aged from 5 months to 12 years, with phimosis were treated by application of a specially designed balloon catheter (patented). 1% dicaine topical anesthesia was used. 3-6 months follow-up showed that all the patients were cured. The procedure is simple, safe and much less traumatizing than the conventional circumcision. The mechanisms of balloon dilation, the age specificity and the anesthesia were discussed. PMID- 1874026 TI - Influence of flexion-extension motion of lumbar spine on lumbosacral dural sac. An experimental study. AB - To analyze the effects of flexion-extension motion of lumbar spine on the position and shape of lumbosacral dural sac, 10 flexion/extension lateral myelograms of cadaver specimens of normal lumbar spine were measured. The results showed that moving from flexion to extension both sagittal diameter and length of the dural sac decreased significantly, the dural sac moved caudally, and the sagittal diameter of the anterior epidural space decreased in the mid-vertebral level but increased in the intervertebral level. The dynamic changes of the dural sac and their influence factors and clinical relevance were discussed. PMID- 1874027 TI - Scanning electron microscopic study of subchondral bone tissues in osteoarthritic femoral head. AB - During total hip replacement for 12 cases of advanced osteoarthritis of the hip joint in aged women, three types of diseased or abnormal articular cartilage with different degrees of severity (white articular cartilage, white and hyperplastic articular cartilage, and yellowish articular cartilage) and ivory bone were obtained together with their subchondral bone tissues. These specimens were processed and studied under scanning electron microscope and were compared with sex- and age-matched non-osteoarthritic femoral head articular cartilage specimens. The following findings were observed: 1. In non-osteoarthritic femoral head, the subchondral bone plate was quite thin. The bone plate connected on its deep surface with the lattice-work of trabeculae of the epiphyseal region. The trabeculae were fine and smooth and some revealed round or spindle-shaped callus resulted from microfracture. 2. In osteoarthritic femoral heads, with increased the severity of the articular lesion, the articular cartilage gradually became thinned out and eventually lost. The subchondral bone plate was markedly thickened. The epiphyseal trabeculae were also thickened and turned rough so that the lattice-work pattern gradually disappeared. The thickened trabeculae finally fused into a large piece of dense bone tissue. No microfracture was detected. These changes were attributable to the increased stress imposed on the subchondral bone tissues as a result of defective articular cartilage. Consequently, the changes on the part of the subchondral bone tissues of the osteoarthritic femoral heads were the sequent, rather than the cause, of the articular lesions. PMID- 1874028 TI - Survey of the use of epidural analgesia in China. AB - It is generally believed that epidural blocks are most widely used in China. However, there is yet no substantial study in this respect. A nation-wide survey appears to be necessary. Questionnaires were sent to 237 hospitals located in 6 geographically wide-scattered areas and to some military hospitals as well. 90 answers were obtained with complete data necessary for this survey. There are 1,304,214 administrations of epidural blocks documented in these 90 hospitals. Of which 38.8% are lumbar, 32% lower thoracic, 23% middle thoracic, 4.6% upper thoracic and 1.6% cervical blocks. These data showed that operations from the neck down to the lower extremities were performed under epidural block without discrimination of puncture location. 98.33% of the blocks were satisfactory to meet the need of operations. Persisting paresthesia occurred in 0.013% of these cases. The incidence of accidental puncture of dura was 0.32%. About 2/3 of these dura punctured cases received 1-4 times of repuncture. No correlation was found between repuncture and development of total spinal anesthesia. Among the complications, incidence of respiratory depression was 0.54%. However, only 5% of these depressed cases needed intubation and artificial ventilation. No signs of dura puncture were noticed, but subarachnoid block did appear in 0.04 of cases. Incidence of total spinal anesthesia was 0.013%. Not all, but a little more than half (54.6%) of the total spinal cases needed intubation and artificial ventilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874029 TI - The Fourth National Conference of the Hand Surgery Section of the Chinese Orthopedic Society. PMID- 1874030 TI - An endodermal sinus tumor in the cerebellopontine angle. AB - Immunohistochemical and ultrastructural findings in a primary intracranial endodermal sinus tumor are reported in this paper. The tumor cells exhibited AFP, CEA and anti-alpha-1-trypsin positive immunoreactivity immunocytochemically. Aggregates of electron-dense material in the extra- and intracellular spaces and amorphous basement membrane-like substance were seen extracellularly by electron microscopy. The clinicopathological, immunocytochemical and ultrastructural features were consistent with the criteria for primary intracranial sinus tumor. PMID- 1874031 TI - Renal hemodynamic and tubular effects of angiotensins II and III. AB - Angiotensin II (ANG II) plays an important role in the regulation of renal vascular resistance, glomerular function and tubular reabsorption. Systemic infusion of ANG II produces dose-dependent decreases in renal blood flow (RBF), glomerular filtration rate (GFR) and filtration coefficient, and increases in filtration fraction. Intrarenally generated ANG II is also critical to alterations in cortical and juxtamedullary glomerular ultrafiltration. On the other hand, pharmacological blockade of the systemical and intrarenal generation or action of ANG II elicits increases in RBF and pressure-associated changes in GFR. In vivo micropuncture experiments demonstrate that peritubular capillary microperfusion of 10(-7) M ANG II results in decreases in single nephron GFR and glomerular capillary pressure. Blockade of ANG II activity by ANG converting enzyme (ACE) inhibitor markedly attenuates, whereas intravenous or peritubular capillary infusion of exogenous ANG II enhances tubuloglomerular feedback (TGF) mediated changes in the stop flow pressure. Moreover, infusion of exogenous ANG II during conditions of ACE blockade partially restores the feedback responsiveness, suggesting a specific role of ANG II as a modulator of TGF system. Besides its effects on intrarenal hemodynamics, ANG II directly or indirectly affects renal sodium excretion. Micropuncture and microperfusion studies have shown that ANG II exerts a dose-dependent biphasic effect on proximal tubular sodium reabsorption via apical Na(+)-H+ exchange. A stimulatory effects of ANG II at low dose (10(-12)-10(-9) M) and an inhibitory effect at higher dose (10(-7)-10(-5) M) have been observed in the cortical and juxtamedullary nephron preparations. The stimulatory effect of ANG II on proximal tubular reabsorption of sodium seems associated with reduction in cAMP and/or activation of protein kinase C, whereas cytosolic free calcium surge activated by ANG II may be part of the cellular message that inhibits proximal tubular reabsorptive function. ANG III, a metabolite of ANG II, also enters substantial influence on renal function. In contrast to the systemic pressor effect, the two peptides are approximately equipotent in their actions on the renal vasculature. Superimposed administration of either ANG II or ANG III during ACE inhibition completely reverses the GFR and renal excretory responses to ACE inhibition. Furthermore, intracerebroventricular injections of ANG II and ANG III in rats inhibit renal nerve activity and cause a comparable renal effect which can be blocked by Ile7-ANG III and potentiated by bestatin, suggesting that the heptapeptide may also play an active role in the regulation of sodium excretion by actions on renal hemodynamics and tubules. PMID- 1874032 TI - Sino-American collaboration in biomedical research & training: American and Chinese Physiological Societies look towards new horizons. PMID- 1874033 TI - Cellular effects of growth hormone on adipocytes. AB - Adipocytes are physiological targets for GH in both growing and nongrowing individuals. In adipocytes that have been deprived of GH for at least 3 h, GH initially produces a response that is characterized by increased metabolism of glucose and inhibition of the lipolytic effects of catecholamines. This insulin like effect disappears within 2-3 h despite continued stimulation and cannot be elicited again unless cells are deprived of GH for at least 3 h. Despite refractoriness to the insulin-like action of GH, the lipolytic effect of GH is evident at this time. Although termination of the insulin-like response and induction of both refractoriness and lipolysis all depend upon synthesis of RNA and proteins, these 3 effects of GH appear to be neither temporally nor causally related. Scatchard analysis of ligand binding data suggests that these various effects are produced by interaction of GH with a single class of receptors. However, since modification of either the hormone or the carbohydrate moiety of the receptor can selectively attenuate either the insulin-like or the lipolytic response, more than one hormone receptor interaction is likely. Northern analysis indicates the presence of at least 2 alternately spliced mRNA transcripts for the GH receptor, and at least 3 different complexes are seen after GH is covalently crosslinked to intact adipocytes. Refractoriness does not result from changes in either the number or affinity of GH receptors, but may result from increased cytosolic calcium. Although the protein kinase C activator phorbol myristate acetate mimics both the insulin-like and lipolytic actions of GH, increased activity of protein kinase C probably does not mediate either action of GH. The intracellular mediators of the diverse actions of GH are unknown at this time. PMID- 1874034 TI - Neuroendocrine control of prolactin secretion: the role of the serotonergic system. AB - The secretion of prolactin (PRL) falls into distinct patterns in mammals. Suckling, stress, cervical stimulation and estrogen all stimulate PRL secretion. The estrogen-induced afternoon PRL surge is circadian in nature and is regulated by the central serotonergic system. Interruption of the serotonergic system by all means blocks the PRL surge. As for the site and mechanism of 5-HT action, it has been shown that 5-HT has no direct effect on the anterior pituitary and its action on PRL secretion may be dissociated from its peripheral cardiovascular effect. Its action may not involve the central dopaminergic system or interaction with the central opioid system. However, it may be stimulating a yet unidentified PRL-releasing factor during specific time in the afternoon of estrogen-treated rats. PMID- 1874035 TI - Evidence for the functional significance of multiple renin forms. AB - Our laboratory demonstrated the existence of 6 forms of renin, (F1-F6) each with a unique isoelectric point (pI). We ascribe the heterogeneity to differences in glycosylation. This heterogeneity has been demonstrated to exist in all animals studied in our laboratory, across a wide evolutionary scale. Multiple forms have been found in fish, amphibians, birds and mammals, including humans. We have been able to demonstrate that hepatic inactivation of the renin forms in humans is different for each form. Isolation and purification of the forms allowed injection of a single form into rats. IV infusion of F4 resulted in a significant natriuresis and diuresis, while the other forms had no significant renal effects. However, if the same forms were infused into the cerebroventricles at a much lower dose, F6 caused a natriuresis. Pretreatment with converting enzyme inhibitor abolished that effect. We were able to show that Spontaneously Hypertensive Rats (SHR) exhibited a renin profile that was altered in a predictable way and was significantly correlated with their blood pressure. The hepatic clearance of each form was also different, so that the forms have different half lives. These data support the hypothesis that renin heterogeneity is dependent upon glycosylation and is functionally significant. PMID- 1874036 TI - Role of afferent renal nerves in the control of vasopressin secretion. AB - Several lines of evidence indicate that the kidneys can influence the secretion of vasopressin. We have reported that electrical stimulation of the renal nerves increases plasma vasopressin concentration in dogs and rabbits, and other investigators have reported that selective stimulation of afferent renal nerves in cats and rats increases plasma vasopressin concentration or the activity of neurosecretory neurons in the supraoptic nucleus. Intrarenal infusion of bradykinin, which is known to excite afferent renal nerves, has also been reported to increase the activity of putative vasopressin neurons in the supraoptic nucleus of rats. Recently, we observed that intrarenal infusion of bradykinin in rabbits increases plasma vasopressin concentration, and that this response is markedly reduced by renal denervation. We have also reported that activation of renal mechanoreceptors by elevating intrarenal pressure increases plasma vasopressin concentration in rabbits, and that this response is blocked by renal denervation. In order to determine if the kidneys participate in the physiological regulation of vasopressin release, we investigated the effect of renal denervation on the osmotic and non-osmotic control of vasopressin secretion in conscious, chronically-prepared rabbits. We found that renal denervation did not significantly reduce the vasopressin responses to hypertonic saline infusion, 24-hour water deprivation, hemorrhage or nitroprusside infusion. In summary, these observations indicate that the kidneys can influence the secretion of vasopressin via the afferent renal nerves. However, the physiological significance of the observations remains to be determined. PMID- 1874037 TI - [Therapeutic strategies in fractures with soft tissue damage]. PMID- 1874038 TI - ["Biological osteosynthesis"]. PMID- 1874039 TI - [Primary soft tissue treatment and soft tissue reconstruction]. PMID- 1874040 TI - [Spongiosa-plasty and transport corticotomy--an alternative or supplementary procedure?]. PMID- 1874041 TI - [Value of computerized tomography and nuclear magnetic resonance tomography in preoperative diagnosis of meniscus lesions and ligamentous lesions of the knee joint]. AB - In a prospective study, 53 patients with chronic complaints and acute injuries of the knee joint, were evaluated by clinical examination, CT-scanning and magnetic resonance imaging (MRI). Subsequently, arthroscopy or an open surgical procedure was performed. A total of 21 patients suffered from meniscal lesions. There were 17 ruptures of the medial and 4 ruptures of the lateral meniscus. In patients with meniscus ruptures, the sensitivity of both MRI and CT-scan was 86%, whereas the specificity of MRI was slightly lower than that of CT-scan. The accuracy and the predictive value were also slightly lower, although the difference was not significant. Fifteen patients suffered from acute or chronic ligament ruptures. In patients with anterior cruciate ligament (ACL) ruptures, all complete ACL ruptures had correctly been diagnosed by CT and MRI. Two out of four partial ACL ruptures were missed by MRI; only one was missed by CT-scan. Three medial collateral ligament ruptures were documented by MRI and two by CT-scanning. The high negative predictive value of CT and MRI can realize a reduction of the amount of diagnostic arthroscopies. PMID- 1874042 TI - [Arthrolysis as a surgical treatment concept of post-traumatic stiffness of the knee joint]. AB - In the period from 1977 to 1989 105 arthrolyses were performed in 102 patients. There were mainly posttraumatic fibroarthroses: 51 consecutive to fractures, 39 after ligamentous injuries, 13 post-infectious of which 11 were also post traumatic and only 2 patients with rheumatological diseases. Remarkable is the increased number of fibroarthrosis after polytrauma (n = 26). The preoperative range of motion was under 30 degrees in 26 patients and 48 patients had a severely limited range of motions between 30 and 60 degrees. The follow-up examination performed in an average of 2 years after the operative mobilization showed that the initial mobility was more than doubled. These results are related to atiology, operative procedure and degree of severity of the preoperative stiffness. Fair to excellent results were obtained in almost 3/4 of the patients. We explain these results by an adapted extraarticular or combined procedure which were used in 63 cases. The open release is backed by an intensive rehabilitation program in which painlessness through PDA and an immediate postoperative continuous passive motion are of most importance. PMID- 1874043 TI - [Conservative therapy of fractures of the thoracic and lumbar spine. Indications, treatment regimen, results]. AB - In this study the results of conservatively treated stable fractures of the thoracolumbar spine in 112 cases are reported. The follow-up of these patients was carried out by clinical and radiological examinations. It proved that functional treatment used in 94% of all cases was superior in its results and lack of pain to Bohler the method according of closed correction and immobilization by cast. The radiological examination showed no coherence between narrowing of the verebra after early mobilization and function of the spine. A three point corset in addition to this therapy seems to be without any advantage. PMID- 1874044 TI - [Osteosynthesis of the clavicle. Indications, surgical technique, results]. AB - The osteosynthesis of the clavicle should be the exception and should only be indicated in the case of complicated fractures. The high rate of pseudoarthrosis given in medical literature, is due to errors in indication, selection of implants and in surgical techniques. Procedures like intramedullar wiring, axial screwing and single cerclage-wire suture are unsuited for osteosynthesis of the clavicle. After osteosynthesis of the clavicle we have found exceptional positive results, with respect to functional, radiological and after subjective evaluation, at a low rate of complication without any consequences occurring in the years to come. These results show, that mainly good or even excellent success can be achieved, at a limited indication, combined with careful surgery and a standardized surgery procedure of osteosynthesis of the clavicle. PMID- 1874045 TI - [Immune competence of human tissue lymphocytes in contact with loosened hip joint prostheses. On the topic of cellular or humoral rejection reaction as the mechanism of loosening]. AB - In several investigations rejections were accused of being a possible cause for the loosening of hip endoprostheses. Using immunocytochemical techniques we studied the number and type of lymphocytes in the tissue adjacent to loosened hip endoprostheses. Tissue samples were taken from 18 patients being reoperated for a loosened endoprostheses. Impressive lymphocyte infiltrates were found in 4 of 18 patients (22%). These infiltrates only consisted of T-cells. In the other samples only few lymphocytes were detected belonging to T- and B-lymphocyte population, respectively. In our patients T-cell mediated rejections were of minor importance for the loosening of total hip replacement. B-cell accumulations were detected in none of the samples. PMID- 1874046 TI - [Therapeutic concept and results of treatment of subcutaneous extensor tendon rupture of the finger end joint]. AB - This study covers treatment and after-treatment of 95 extensor tendon injuries of the DIP-joint in 94 patients over a period of 3 years. Tendon injuries were classified into 4 types according to Suckert et al. and the final results were evaluated using a modified Riedeberger and Zeumer scale. In recent subcutaneous tendon injuries conservative therapy is indicated, depending on the primary extension deficit (less than 20 degrees = modified Stack splint, greater than 20 degrees = Mommsen plaster of Paris or special dressing). Chip fractures should be stabilized by pull-out suture. PMID- 1874047 TI - [A simple, rapid and economical method of distal interlocking nailing in upper and lower leg intramedullary nailing]. AB - Distal interlocking of intramedullary nails is associated with a relatively high radiation exposure. For the reduction of fluoroscopy time and surgeon's hands irradiation, many devices have been developed so far. In this paper, a simple free-hand-technique is presented. The mean fluoroscopy time in 30 femur and 10 tibia interlocking intramedullary nailing procedures was one minute. The technique avoid the central beam of the fluoroscope and does not require specific instruments. The technique is based on the axial placement of a 2 mm K-wire in the interlocking screw holes. A centrally perforated 4.5 mm drill is placed over the K-wire. Therefore in this technique a perfect centrally placement of the K wire is not necessary. The drill is guided by the K-wire thereby avoiding complications such as drill failure or deviation of the drill direction. PMID- 1874048 TI - [Bilateral arm amputation caused by high voltage burns in childhood: stump reconstruction by tissue expansion and fibula transfer]. PMID- 1874049 TI - [Treatment of open patella fracture with external mini-fixator]. PMID- 1874050 TI - [Bilateral carotid artery stenosis following severe craniocervical trauma]. PMID- 1874051 TI - [Modification of the Stellbrink external fixator for flexible and expanded use in hand surgery]. PMID- 1874052 TI - [Comment on the contribution by C. Krettek et al.: Stabilizing open tibial fracture with the external fixator. Are there advantages to an additional osteosynthesis?]. PMID- 1874053 TI - [A revolutionary operation]. PMID- 1874054 TI - [Significance of composite scoring of biochemical monitoring in fetal distress]. AB - Urinary E/C ratio, maternal urinary meconial index (UMI), human placental lactogen (hPL) and pregnancy specific beta-1 glycoprotein (SP1) were determined by biochemical and immunologic method. The accuracy of composite scoring method was compared with that of individual index. The results show that composite scoring method was better than the single index in predicting and diagnosis of fetal distress. PMID- 1874055 TI - [Use of fetal heart rate scoring system in intrapartum fetal monitoring]. AB - A scoring system of intermittent 5-second successive fetal heart rate auscultation was devised for intrapartum fetal monitoring. Its use among 150 cases in two hospitals, yielded a negative predictive rate of 93.8% and a positive rate of 71.4%, higher than that of the routine auscultation method. The scoring system was also well correlated with the umbilical blood gases values. Hence, it is recommended for intrapartum fetal monitoring, especially, where electronic monitoring is not available. PMID- 1874056 TI - [Pathological analysis of 76 placentae in fetal distress]. AB - The result of pathological analysis of 76 placentae and their appendices from clinically diagnosed fetal distress in year 1985-1989 is here presented. The findings could be classified into 4 groups; lesions due to disturbance of maternal blood flow and villous ischemia or hypoxia; retardation of development and malformation of villi; lesions due to haematogenous and ascending infection and pathological changes of the umbilical cord. The clinical significance of these pathological changes was discussed. We suggested that some lesions such as villous growth retardation, placental haemangioma, choriangiosis, infection of the placenta, single umbilical artery etc, could cause fetal distress, and villitis, single umbilical artery could sufficiently impair placental function so as to retard fetal growth or cause fetal malformation. The etiology of some placental lesions needs further study. PMID- 1874057 TI - [Morphology of placental lobes and clinical pathophysiology in fetal distress]. AB - In order to make a basic study of the etiology, clinical pathophysiology and prevention and management of the fetal distress, an investigation of the placental coefficient, pathomorphology, immunochemistry, and 6 other items were carried out. The placenta lobes of 357 cases with fetal distress were need and a corresponding control was established in each case. The results indicate that the rate of infection of the placenta in fetal distress was 39.5%. The placental coefficient in comparison with the control showed a significant increase (P less than 0.05). Edema of the villi and disease of the villous vascular membrane was prominent. The cytotrophoblast, Hofbauer cell showed cellular compensation proliferation. Estradiol reception (E2R) and progesterone receptor (PgR) were positive mainly in the cyto-trophoblast. The rate of positive finding of Carcinoembryonic Antigen (CEA), AFP and Lysozyme was greater in the fetal distress group in comparison with the control (P less than 0.05). The results indicate that in pregnant women with fetal distress or with risk factors for fetal hypooxygenimia, the administration of anti-infection agents, and improvement of the villus blood circulation as well as giving of anti-amine agents may be beneficial in prevention and management of fetal distress. PMID- 1874058 TI - [Clinical analysis of 1704 cases of fetal distress]. AB - From Oct 1985 through Sept 1986 and from Oct 1988 through Sept 1989, a total of 1,704 cases were clinically diagnosed as having fetal distress. The results of analysis showed no significant differences (P greater than 0.05) between fetal distress and fetal sex, and age of pregnancy women respectively (P greater than 0.05), but there was a significant difference between fetal distress and gestational weeks. (P less than 0.01) and birth weight (P less than 0.05). The highest incidence occurred in postterm pregnancy. The number of neonatal asphyxia cases with fetal distress accounted for 61.08% of the total of neonatal asphyxia. The more indexes of the fetal distress, the higher is the incidence rate of asphyxia neonatorum. Among the complications of pregnancy, the fetal distress rate due to pregnancy induced hypertension is the highest. The results suggested that by using multiple item examinations, early diagnosis of fetal distress and prompt management are possible to decrease the asphyxia rate and the prevention of complications of pregnancy is important to reduce the fetal distress. PMID- 1874059 TI - [Immunocytochemical localization of human chorionic gonadotropin and placental lactogen in normal placentae]. AB - Preliminary observations on immunocytochemical localization of human chorionic gonadotropin (hCG) and human placental lactogen (hPL) were made in 35 placentae of normal pregnancy at various stages of development. By analysing the processing regularities of the two hormones and comparing the characteristics of immunocytochemical localization and hematoxylin-eosin stain on various trophoblasts in the normal placentae, the findings showed: (1) presence of the three types of trophoblasts, namely, cytotrophoblast (CT), intermediate trophoblast (IT), and syncytiotrophoblast (ST) was confirmed in normal placentae of first-trimester pregnancy. (2) IT has distinctive immunocytochemical features that distinguishes itself from CT and ST. In the first-trimester, ST contains a large amount of hCG which sharply diminishes thereafter, but hPL in ST increases with the fetal age. IT contains hPL all through the pregnancy period and the peak value occurs in the second trimester. CT is devoid of hCG and hPL. The results indicated: (1) IT is more like ST but different from CT. (2) IT contains chiefly hPL and hCG only locally in early pregnancy which demonstrates that the processing of hPL is in the more well differentiated cells whereas hCG is in the less differentiated cells. PMID- 1874060 TI - [Reproductive activities as risk factors of epithelial ovarian cancer: a case control epidemiologic study]. AB - A case-control study involving 112 patients with pathologically confirmed epithelial ovarian cancer and 224 randomized community controls matched to the cases on age was conducted in the Metropolitan Beijing Area. The results showed that parity, gravidity and their related factors play an important role in the genesis of epithelial ovarian cancer. A good inverse relationship was observed between the number of full term pregnancies and the magnitude of relative risk. Term pregnancy seemed to have a stronger protective effect than aborted pregnancy and an adequate protection can be achieved by three term pregnancies. At the same time, the number of ovulatory years was positively correlated with the rise of the relative risk. In addition, it was found that age at the first pregnancy was not related to the occurrence of ovarian cancer as indicated in the literature. PMID- 1874061 TI - [A clinical analysis of 317 cases of salpingo-anastomoses]. AB - Influences of various factors on status pregnancy in 317 women having had salpingo-anastomoses were analyzed. All these cases, aged 21 to 45, had end to end operation under direct observation. Through 1-5 years' follow up, two of the 317 women were found to be restricted, 295 were pregnant or already delivered. The re-potent rate was 99.3%, while the re-pregnant rate 93.1%. No statistically obvious disparity in pregnancy rate was found as regard to age, tubal ligation technique site of anastomosis. However, there was influence over the pregnancy rate by the length of the remaining tube and oviduct inflammation. This paper also discussed on the anastomosis method, length of contraception period, observation period and the choice of stents. PMID- 1874062 TI - [Clinical significance of the determination of cellular DNA content in gynecologic neoplasms]. PMID- 1874063 TI - [An experimental study on artificial blood vessel bridge in the jugular veins]. PMID- 1874064 TI - [The effect of teeth arrangement in maxillary complete denture on the stress distribution of bone tissue--photoelastic stress analysis]. AB - In this paper, we make a study about the effects of 6 different kind of arrangement of the 1st molar in maxillary complete denture on the stress distribution of bone tissue. In intercuspation position, it is well-distributed when the artificial teeth are arranged on the top of alveolar ridge. There are stress concentration in the bone tissue. When the long axis of the teeth incline bucally or the teeth migrate away from the ridge center line. When the ridges relation is disharmonious, it is better that the teeth incline do not over 30 degrees buccally and the teeth migration do not over 5 mm horizontally. PMID- 1874065 TI - [Extra-articular rearrangement of temporomandibular joint internal derangement and associated neuromuscular disorders]. AB - This report introduces a new method for treatment of TMJ internal derangements and associated neuromuscular disorders. This operation consists of two main surgical procedures: (1) To detach the muscular attachments of masseter, temporal, and internal pterygoid muscle from the mandible and to detach the external pterygoid muscle from the external pterygoic plate for eliminating the neuromuscular disorders. (2) To reposition the condylar head from the glenoid fossa after making a vertical osteotomy on the posterior portion of the ramus for eliminating the internal derangements of the joint. Therefore, the causes of considerable embarrassment of TMJDS could be eliminated and the iatrogenic trauma to the joint could be avoided. Since 1987-1990, 15 cases have been successfully performed. PMID- 1874066 TI - [Use of direct immunofluorescence in the diagnosis of diseases of oral mucous membrane]. PMID- 1874067 TI - [The influence of natrium fluoride on the diffusion of Ca++ in protein solution of artificial pellicle in vitro]. PMID- 1874068 TI - [Three-dimensional analysis on facial structures correlation of the facial aesthetics of Chinese]. AB - The frontal facial moire photographs of 50 male and 50 female young adults with esthetic face strictly selected from Chinese population on the basis of the standard were taken and analysed three-dimensionally. It was found that not only significant correlation but also a statistical linear regressive equation existed between nose, lip and chin, between lip and chin, and between the width and the height of the face. So it is possible, on the basis of a known variable, to calculate another variable by means of the mathematical equation, which will provide quantitative variables for the orthognathic and the plastic surgery creating the esthetic face. PMID- 1874069 TI - [Factor analysis of anterior deep bite malocclusions and its significance]. AB - A series of 38 measurements was derived from lateral cephalometric radiographs of a large sample of 195 subjects including 130 patients with deep bite malocclusion and 65 control subjects with normal occlusion. These measurements were subjected to a factor analysis which resulted in a series of 8 factors extracted which accounted for 83.3% of the total variance. These factors in rank order of their percentage sample variability were as follows. Factor 1: vertical height; Factor 2: protrusion-retrusion of anterior teeth; Factor 3: protrusion of mid-face; Factor 4: horizontal position of posterior border of the jaws;Factor 5: protrusion of the chin; Factor 6: protrusion of lip; Factor 7: divergence of the face;Factor 8: inclination of upper Lip. The factor scores were further used in a multiple regression analysis in order to predict other cases. The data-reduction method involving a factor analysis would seem to have great significance of clinical application. PMID- 1874070 TI - [Relationship between radiology and prognosis in sarcoma of jaw]. AB - A new radiologic grading based on the comprehensive studies of radiographs of 76 cases of jaw bone sarcomas is suggested. Cortical expansion or sclerotic rim is regarded as grade 1, localized destruction with sharp edges as grade 2, moth eaten destruction as grade 3, and diffuse destruction as grade 4. A close relationship exists between the rate of 5 year survival and the radiologic grading which is considered to be one of the four main X-ray criteria for evaluation of prognosis. The other 3 criteria are the extent of destruction, the tumor location, and the changes of the teeth and periodontal space. PMID- 1874071 TI - [Cell kinetics of oral leukoplakia]. AB - The cell kinetic characteristics of 28 cases of oral leukoplakia were studied by in vitro double labelling with 3H-thymidine and autoradiography. As compared with normal oral mucosa, there were significantly higher LI, shortened Tc and increased labelled basal cells in the leukoplakia with epithelial dysplasia, and similar changes in LI, Tc and labelled basal cells were also found in several cases without epithelial dysplasia which were clinically homogeneous or evidently caused by tobacco use. The expansion of labelled cells was often found in the epithelium with shortened, even disappeared rete pegs. The significances of the findings described above was discussed. The authors consider cell kinetics study may be useful in monitoring the dangerous cases of leukoplakia. PMID- 1874072 TI - [Oral and maxillofacial multiple primary cancers]. AB - Among 2989 patients with oral and maxillofacial cancers treated in our department from 1953 to 1985, 49 cases (1.63%) had the multiple primary lesions. The double primary cancers occurred in 44 cases (89.8%), three or more in 5 cases (10.2%). The multiple foci in an organ happened in 16 cases, different organ of systems in 23, and two systems in 10 cases. The followup in 49 cases (92.4%) for 3-27 years revealed the survival rates as follow: 76% (3 yrs), 69% (5 yrs), 42% (10 yrs), and 33% (15 yrs). The aggressive surgical intervention should be performed in oral and maxillofacial multiple primary cancers for a good therapeutic result. PMID- 1874073 TI - [Application of tricalcium phosphate in one visit root canal treatment]. AB - This paper reports the successful use of tricalcium phosphate (TCP) as periapical barrier material in animal experiments and clinics. The results of animal experiments showed that TCP had good biocompatibility with periapical tissues. At 6 weeks there were osteoids deposited on the surface of TCP. At 12 weeks osteogenesis occurred around the TCP particles and combined each other closely. At 24 weeks around the periapex there were bone deposits and a tendency of apical closure. On the basis of experiments TCP was used to treat 17 chronic periapicitis in 15 patients. All cases were young permanent teeth with immature roots. It is suggested that TCP can be applied directly in chronic periapicitis with open apices of young permanent teeth. From 6 to 12 months after filling with TCP the X-rays showed that radiolucencies reduced or eliminated, bone trabecula formed and periapical lamina dura reestablished. PMID- 1874074 TI - [Accuracy and the repeatability of using intra-oral wax record method in registering the protrusive condylar guidance inclination]. PMID- 1874075 TI - [Prognostic factor analysis of squamous cell carcinoma of buccal mucosa]. PMID- 1874076 TI - [A study of forced tooth movement. An observation of early histo-pathologic and ultrastructural changes in compressed periodontal ligaments of rats]. PMID- 1874077 TI - [A longitudinal study of bone age]. PMID- 1874078 TI - [Effect of tetrandrine and verapamil on left ventricular diastolic and systolic function in essential hypertension]. AB - By using apexcardiography and echocardiography, the diastolic and systolic function of 34 hypertensive patients were studied. The results indicated that left ventricular (LV) hypertrophy is one of the important factors in impairing LV diastolic function in essential hypertension. By using self-control method, Verapamil(V) was injected intravenously. Relative A wave to total diastolic amplitude (A/D), total apexcardiographic relaxation time index (TARTI), diastolic amplitude time index (DATI) and PEP/LVET were measured. After 5 half-lives of V, intravenous Tetrandrine (T) was given, all the measurements were repeated in the same way. The data revealed that A/D, TRATI and DATI improved significantly after intravenous T and V as well, yet PEP/LVET showed no significant change. It, therefore, seems clear that both T and V could induce a significant improvement in LV diastolic function without any apparent adverse influence on systolic function. PMID- 1874079 TI - [Pulmonary artery compliance and its relation with pulmonary hemodynamics in patients with chronic obstructive pulmonary disease]. AB - In order to investigate pulmonary artery compliance (Cpa) and its relation with the clinical conditions and the other parameters of pulmonary hemodynamics in patients with chronic obstructive pulmonary disease (COPD), we performed right heart Swan-Ganz catheterization in 146 COPD patients and measured their Cpa with Engelberg's method. The results showed that Cpa of BB type patients was lower than that of PP type ones; patients with pulmonary hypertension or cor pulmonale had lower Cpa than those without. These results suggest that Cpa in COPD patients decreases as their clinical condition worsens. Cpa had close relation with other pulmonary hemodynamic parameters. It had significant negative correlation with pulmonary arterial mean pressure, pulmonary vascular resistance and right ventricular stroke work index and significant positive correlation with cardiac index and stroke volume index. Using Engelberg's method as the standard, we also compared Reuben's, Wang's and Zhong's methods which are all simpler than Engelberg's method for measuring Cpa clinically. The results showed that Cpa measured with Wang's method was the closest to that measured with Engelberg's method. PMID- 1874080 TI - [Hemodynamic changes in patients with chronic cor pulmonale secondary to COPD and effect of sodium nitroprusside administration]. AB - Pulmonary hemodynamic changes were studied with Swan-Ganz right heart catheterization in 19 patients with chronic cor pulmonale secondary to COPD. HR, RVP, PAPM, PVR, PCWP, RWI and PaCO2 were significantly higher and PaO2 and PH lower in patients with decompensated than those with compensated heart function. Nitroprusside lowered effectively pulmonary arterial pressure and pulmonary vascular resistance. Meanwhile, the drug also lowered PaO2 when the patient was breathing air but did not so or even increased it when breathing oxygen. PMID- 1874081 TI - [A diagnostic approach to primary malignant lymphoma of the intestine]. AB - Thirty-one cases of primary malignant lymphoma of the intestine diagnosed since 1980 were studied. Being reviewed the clinical data all cases were reclassified histologically according to Isaacson's new classification in 1988. The immunohistochemical staining were performed with epithelial, B-cell, T-cell and histiocytic markers for early diagnosis of the disease. The results showed male, youth and laborer predominance with a short courses and poor prognosis, Colonoscopy and X-Ray found "malignant lesions" in characteristics. Histologically, High-grade and B-cell lymphoma were predominance. MALT lymphoma and the combination of low to high-grade lesions were found. Immunohistochemical staining is quite helpful in the differentiation of carcinoma, malignant histiocytosis. Finally, the procedure of early diagnosis of the disease was proposed. PMID- 1874082 TI - [Extramedullary relapse in acute leukemia]. AB - Thirty four cases of isolated extramedullary relapse after complete remission of acute leukemia were reported. The relapse took place in central nervous system (CNS), genito-urinary system, skin, serous cavity, tonsils, lymph nodes, liver, spleen, gastro-intestinal tract, pancreas and ocular fundus. These 34 cases of isolated extramedullary relapse of leukemia was found in 206 cases with complete remission, constituting 16.5% of the total. In order to discover CNS relapse with no symptoms and signs, the author strongly suggest that cerebrospinal fluid examination be carried out periodically. If some symptoms signs in the patient can not explained by infection, congestion or other causes, extramedullary relapse should be considered and further examination and appropriate treatment are needed. PMID- 1874083 TI - [Cerebellar infarction and its assistant examination]. AB - The clinical manifestations of cerebellar infarction are often non-particular and it is difficult to make such a diagnosis clinically. Diagnosis was based on pathology previously. Most of the cases were overlooked while still living and the true morbidity was not known. CT scan has made the diagnosis of this disease possible clinically in some patients, but CT is still not an ideal instrument for diagnosing this disease because of the interference by bony artifacts of posterior fossa. The advent of MRI made it possible to distinguish cerebellar infarction safely and easily. It is not the most powerful tool for diagnosing this disease. The authors reported 15 cases of cerebellar infarction diagnosed by clinical manifestation, neuroimages and pathology and pointed out that further knowledge of this disease is needed. PMID- 1874084 TI - [Clinical analysis of 130 patients with fever of unknown origin]. AB - Hospital records of 130 patients with fever of unknown origin (FUO) from 1985 to 1989 were studied. Etiologic diagnoses were made in 117 (90%) patients, 60 (46.1%) patients had infections, 22 (16.9%) neoplasms, 19 (14.6%) connective tissue diseases, and 16(12.3%) various diseases grouped under "miscellaneous", 10% of the FUO cases remained undiagnosed and the death rate was 13.8%. This clinical analysis showed that infection was the most frequent cause of FUO in this series. PMID- 1874085 TI - [Changes in leucocytic estrogen receptor levels in patients with gynecomastia]. AB - The number of estrogen receptor (ER) in human peripheral leucocytes in 13 men with gynecomastia were measured by radioligand binding method. The results were compared with those of 13 sex-and age-matched healthy subjects. It was found that the number of ER in leucocytes was significantly increased in gynecomastia (Rs of leucocytes were 1054 +/- 254 sites/cell). It suggested that increase of ER levels play an important role in the pathogenesis of gynecomastia. PMID- 1874086 TI - [The prognostic significance and correlation of ventricular late potentials with programmed electrical stimulation in patients after myocardial infarction]. AB - Seventeen patients (pts) after myocardial infarction (MI) were studied with signal-averaged electrocardiograph and cardiac programmed electrical stimulation (PES). In 7 pts with late potentials (LPs), sustained ventricular tachycardia (SVT) was induced in 6 cases (6/7, 85.7%); while it was induced only in 3 cases the 10 pts without LPs (3/10, 30%). Both have significant difference (P less than 0.01). During following observation, pts with LPs and SVT induced 5 of the 6 appeared clinical SVT or ventricular fibrillation (VF) repetitiously, and 1 died from sudden cardiac death. They also have significant difference (P less than 0.001) with pts without LPs and SVT not induced. These results suggests that LPs is a significant index for predicting future events and its combination with PES is helpful to screen high-risk pts after MI. PMID- 1874087 TI - [Relationship between electrocardiographic pattern and angiographic findings in inferior myocardial infarction]. AB - The relationship between electrocardiographic pattern and angiographic features was assessed in 86 patients with inferior myocardial infarction. Although the occurrence of inferior Q wave was similar in patients with isolated left circumflex (LCX) or right coronary artery (RCA) occlusion, lateral Q wave and abnormal R wave in lead V1 were more frequent in the former. In patients with LCX related infarction, abnormal R wave in lead V1 associated with inferior and/or lateral Q waves may indicate left ventricular dysfunction, total occlusion of the LCX without collateral circulation, and high cardiac event rate during longterm follow-up. PMID- 1874088 TI - [Changes in parameters of hemorheology and circulation 6-keto-PGF1 alpha and TXB2 in dilated cardiomyopathy]. AB - The changes in 12 parameters of hemorheology were observed and the levels of peripheral plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) measured in 35 cases of dilated cardiomyopathy (DCM), including 6 peripartum cardiomyopathy (PCM). We found that there is of hyperviscosity in DCM, the causes were decrease of erythrocyte deformability, increase of red blood cell aggregation, increase of plasma fibrinogen and TXA2 level and decrease of plasma 6-keto-PGF1 alpha level. PMID- 1874089 TI - [Hemolytic reaction resulting from propafenone administration]. AB - Although adverse reactions of many kinds caused by propafenone have been observed, yet there has been no documented report of hemolytic reaction. Four episodes of hemolytic reaction in three patients receiving intravenous propafenone were reported. These reactions took place a few hours after the administration and one of the episodes was complicated with acute left ventricular heart failure and shock. Cessation of propafenone administration together with relevant therapeutic measures tide the patients over and hemolysis disappeared in several hours. Toxicological examination revealed no physical or chemical deterioration and biological contamination of the remaining medication and no such reaction was noted when the drug of the same batch was given to other patients. It is considered that the hemolytic episodes were related to allergic constitution of the patients. Judging from the clinical manifestations, these episodes were hemolytic reactions of immune complex type. PMID- 1874090 TI - [Diagnosis and treatment of rapidly progressive glomerulonephritis. An analysis of 20 cases]. AB - In order to know the incidence and character of rapidly progressive glomerulonephritis (RPGN) in China, 20 patients with RPGN were analysed and 10 of them followed. Their diagnosis were confirmed by biopsy showing extensive crescent formation. Five patients were rebiopsied. RPGN was found in about 3% of the patients with glomerulonephritis in our center. Only one case was mediated by anti-GBM antibody, while the other 19 by immune complex. Prodromal infection was common (12/20). Hematuria, nephrotic syndrome and hypertension were found in 20, 15 and 12 patients respectively. Five patients without special treatment died of renal cause within 6 months. Intensive treatment (pulse methylprednisone or plasmapheresis) was effective in all of the four cases with cellular crescents. After the treatment, their renal function improved with decrease of proliferation and crescent formation as shown by rebiopsy. However, deterioration of renal function reappeared after 3 months to 3 years in three of the cases. It is shown that in China, RPGN was predominantly mediated by immune complex and is associated with a high incidence of prodromal infection. Clinically, nephrotic syndrome was more frequently seen here than in western countries. For improvement of the prognosis, it is necessary to pay attention not only to earlier diagnosis but also to protection of renal function after intensive therapy. PMID- 1874091 TI - [Leukemia and solid tumor]. AB - 3 cases of leukemia after solid tumor and 2 cases of solid tumors after leukemia were reported. The features of leukemia after solid tumor and the relationship between the solid tumor and leukemia, as well as the possible pathogenetic factors of the secondary malignancies were discussed. PMID- 1874092 TI - [The significance of immunoblot in serodiagnosis of cysticercosis cellulosae]. AB - 50, 92 and 30 samples collected respectively from cases with cysticercosis cellulosae, other parasitic diseases and normal controls were examined with SDS gradient (5-20%) polyacrylamide-gel electrophoresis and immunoblot. The results showed that 26 KD protein band of the cysticercus antigen is highly specific for cysticercosis and no cross reaction could be seen in patients with other parasitic diseases, especially hydatid disease, and healthy controls. As we know that the cysticercus antigen usually has a high cross-reaction rate with hydatidosis by ELISA method, the positive rate of this test for cysticercosis is 70% in comparison with 80% and 76% of ELISA and CFT respectively and the difference in the figures of these three tests has no statistical significance. Our study suggested that this method is valuable in clinical diagnosis and epidemiological surveys for research work on cysticercosis cellulosae. PMID- 1874093 TI - [Rapid diagnosis of typhoid fever and its treatment with antibacterial agents]. PMID- 1874094 TI - [Clinical study of perioperative changes in plasma potassium]. AB - Forty adult patients undergoing non-cardiac major surgery were divided into 2 groups. Group A (n = 20) was anesthetized by balanced intravenous procaine anesthesia and group B (n = 20) by epidural block. Blood volume, urine output, potassium in plasma as well as urine, pH, glucose, aldosterone, cortisol and insulin were measured from 24 hours before operation to 48 hours after operation. Evident perioperative trend of hypokalemia in patients with normal renal function was most likely due to the following factors: potassium loss prior to operation, improper pre- or post-operative replacement of fluids, perioperative stress, increasing of blood insulin and urine potassium excretion. Our results run against to the general concept that it may not be necessary to supply potassium with 72 hours after operation. PMID- 1874095 TI - [Studies of midazolam, diazepam and thiopentone on respiratory and cardiovascular function during induction anesthesia]. AB - In this study, the effects of midazolam (M), diazepam (D) and thiopentone (T) on respiratory and cardiovascular systems were compared. The patients were randomly divided into 6 groups, besides minute ventilatory volume (MV), onset of induction and cardiovascular changes were also observed. Induction was performed by a bolus injection of one of the following: midazolam (0.3 mg/kg), diazepam (0.3 mg/kg) or thiopentone (5 mg/kg). Five minutes later, 5 micrograms/kg fentanyl and 1.5-2.0 mg/kg succinylcholine were administered. The results showed that: (1) Inhibitory effect on MV was not prominent and similar after use of midazolam and diazepam but was remarkable after thiopental; (2) As for the onset, midazolam was faster than diazepam but slower than thiopentone; (3) Hemodynamic changes of midazolam, diazepam and thiopentone were similar, however during intubation, cardiovascular response was the least in midazolam, diazepam the intermediate and thiopentone the most significant. We conclude that midazolam is a water-soluble, safe and effective inductive anesthetic with its short eliminated half-life period, and much lesser venous irritation, and it is certainly superior to both diazepam and thiopentone. PMID- 1874096 TI - [Effects of fasting and infusion of acid-base balance, electrolyte and plasma glucose level in children during operation]. AB - We studied the effects of fasting and infusion different fluid on acid-base balance, electrolyte and plasma glucose level in 50 children during operation. After whole night fasting, 26 of 44 children (59.1%) were found to have metabolic acidosis, and 5 of 42 children (11.9%) have hypokalemia. The serum K+ level of 30 of 42 children (71.4%) and the serum Na+ level of 6 of 48 children (12.5%) were lower than normal. The serum Cl- level of 21 of 48 children (43.8%) was higher than normal. The serum glucose level of 6 of 48 children was lower than normal. One of 48 children (2.1%) had hypoglycemia. The effects of infusing deferent fluids on acid-base balance, electrolytes and plasma glucose level were compared. The results showed that in patients infusing 10% dextrose with Ringer's solution or 5% Dextrose with normal saline, the plasma glucose level, electrolytes maintained at the normal level or acidosis corrected significantly. It is suggested that 10% dextrose with Ringer's solution and 5% dextrose with normal saline are infused during operation for children. PMID- 1874097 TI - [Hypoxaemia during transportation of patients after anesthesia and upper abdomen surgery]. AB - The incidence of hypoxaemia was studied in 100 patients breathing room air during their transportation from the operating room to the recovery room. Hypoxaemia (SaO2 less than 90%) occurred in 24 (24%) patients. Oxygen saturation rose quickly above 95% when oxygen was administered. The causes of hypoxaemia are discussed. Quick transportation and oxygen supply were recommended. PMID- 1874098 TI - [Cerebral protection in neurosurgical anesthesia]. AB - We present herein clinical experience of neurosurgical anesthesia and cerebral protection in 66 cases, including 27 with supratentorial mass, 28 posterior fossa tumor and 11 cerebral vascular deformity. Our methods for the control of intracranial pressure (ICP) and cerebral blood flow (CBF) during neurosurgical anesthesia were as follows: (1) avoidance of the drugs adversely influenced on ICP; (2) use of lidocaine iv. infusion; (3) prevention of hypercapnia; (4) maintenance of adequate perfusion of vital organs; (5) drainage of cerebrospinal fluid if necessary; (6) use of free radical clearing agents. We conclude that they are key points of effective control of ICP and maintenance of CBF so as to prevent cerebral ischemic effect on neurological function. PMID- 1874099 TI - [Clinical study on changes in insulin, C-peptide and glucagon during cardiopulmonary bypass]. AB - Insulin, C-peptide and glucagon levels in plasma from 13 patients during cardiopulmonary bypass (CPB) were measured. Insulin level was higher during and after CPB than the level before operation (P less than 0.01 or 0.01 less than P less than 0.05). C-peptide level during and after CPB was much higher than the level before operation (P less than 0.01). There were no changes in glucagon level in CPB patients. The mechanism of these changes and clinical significances were discussed. PMID- 1874100 TI - [Internal intussusception of the rectum. An analysis of 62 cases]. AB - In 62 cases of internal intussusception of the rectum, 21 were treated surgically. Their clinical features included serious dyschesia demanding longer time and strength, tenesmus, and slender stool. Digital examination of the rectum, proctoscopy, and colonoscopy usually showed no abnormalities, while defecography could show the presence and severity of internal intussusception. Parenchymal diseases of the rectum such as carcinomas should be ruled out before surgical correction. Operative measures included rectal suspension raising of the pelvic floor, resection of the redundant sigmoid colon, and the pathogenesis of the disease. PMID- 1874101 TI - [Doppler ultrasonic diagnosis for arterial occlusive disease in the lower limbs]. AB - Measurement of segmental arterial pressure by Doppler ultrasonography and Doppler arterial tracing in the lower extremity has become a widely used noninvasive diagnostic technique for arterial occlusive diseases. One hundred and twelve limbs with arterial occlusive disease (aortoiliac 45, superficial femoral 13, popliteal 11, aorto-iliac-femoro-popliteal 35, and tibiofibular arterial segments 8) were evaluated by both angiographic and Doppler ultrasonic techniques, Angiographic findings showed that ultrasonic diagnosis was accurate in 86% of aorto-iliac-femoro-popliteal arterial lesions, in 92% of superficial femoral arterial lesions, and in 100% of the remaining lesions. We believe that the diagnostic accuracy of Doppler ultrasonography could be further improved with the help of segmental arterial pressure measurement using 4 separated narrow cuffs and blood stream tracing technique. PMID- 1874102 TI - [Internal fixation of fractured ribs with Kirschner wires for serious traumatic chest instability]. AB - Internal fixation of fractured ribs with kirschner wires was done in 14 patients with serious traumatic chest wall instability. Four of these patients had fracture of prothorax ribs, and 10 fracture of lateral thorax ribs. This method can not only stabilize the chest wall but also reduce the fractured ribs. It is an ideal treatment for serious traumatic chest wall instability. In this paper, operative opportunity, indication and the main technical points of surgery are discussed. PMID- 1874103 TI - [Repair of large soft tissue defects in the lower extremity of children by bilateral latissimus dorsi myocutaneous flap transference]. AB - Large soft tissue defects of the lower extremity of 8 children was repaired with latissimus dorsi myocutaneous flaps. The age of the children ranged from 6 to 9 years. Both functional recovery and cosmetic appearance of the repaired limbs were satisfactory. Cross-bridge vascular anastomoses were used in four cases because no vessels were available for anastomosis at the recipient site. No significant functional impairments have been noted at the donor site. Operative techniques, indications for this procedure and related problems are discussed. PMID- 1874104 TI - [Changes in oxygen extraction rate after craniocerebral injury]. AB - Changes of oxygen metabolism were observed in 8 experimental dogs and in 9 patients with head injury. Each dog harbored a bag in the epidural space, and was injected normal saline. The ICP was raised to 13.3 kPa and to 20.0 kPa respectively. Arterial oxygenation declined and mixed venous oxygenation went up when the ICP was raised to the given level and maintained for 30 minutes. The oxygen extraction rate decreased from 25.00 +/- 5.40% to 21.50 +/- 4.60% (P less than 0.01) at the ICP level of 20 kPa. Tissue hypoxia was observed in all patients. Although PaO was higher than inspiring air when patients inhaled 50% oxygen. Tissue hypoxia was not improved. The results suggest that the patients head injury is complicated by not only hypoxemia but decrease of oxygen extraction in tissue and organs. We consider that the alteration is responsible for multiple organs failure injury. PMID- 1874105 TI - [Polypoid lesions of the gallbladder. Clinical and pathological correlations]. AB - Fourty patients (21 males, 19 females; mean age 43.95 +/- 11.58 years) had polypoid lesions of the gallbladder, which were confirmed surgically and pathologically. The incidence of the disease was 15.8% in patients undergoing cholecystectomy and 1.4% in patients having ultrasonography. In the 40 patients, 23 (57.5%) had cholesterol polyps, 5 (12.5%) inflammatory polyps, 4 (10%) adenocarcinomas, 3 (7.5%) xanthomatous polyps, 2 (5%) papillary adenomas, 1 mixed polyp, 1 neurofibroma, and 1 adenomatoid proliferative polyp. The mean age of patients with nontumorous polyp was 41.27 +/- 10.16 years. In these patients, 78.8% had polyps less than 5 mm in diameter, and 69.7% had multiple lesions. However, the mean age of patients with tumorous polyp was 56.71 +/- 9.79 years and 71.4% of the patients had polyps more than 5 mm in diameter and 85.7% single lesions. 72.5% of the patients had clinical symptoms. Polyps were detected ultrasonographically, but one third of them were overlooked by either cholecystography or CT. Nomenclature, pathological classification and management of the lesions are discussed. PMID- 1874106 TI - [The effect of bile duct pressure on cholangiovenous reflux. A clinical study]. AB - The measurement of the filling pressure of the bile duct during the process of endoscopic retrograde catheter cholangiography, and the determination of blood culture and blood iodine before and after cholangiography were carried out to probe into the effect of bile duct pressure on cholangiovenous reflux. In 32 cases, 2 had positive blood culture after cholangiography, with a bile duct pressure being 2.98 kPa and 3.72 kPa respectively. Nineteen cases with a pressure below 2.94 kPa showed negative blood culture. In 10 cases with a bile duct filling pressure below 2.16 kPa, no increase in blood iodine was noted whereas, blood iodine level was increased in 5 out of 9 cases (55.6%) with a bile duct filling pressure between 2.16-2.94 kPa, and in 9 out of 13 cases 69.2% with the pressure greater than 2.94 kPa. We believed that during direct cholangiography, the bile duct pressure should be lower than 2.94 kPa in order to prevent the complication of bacteremia. For patients hypersensitive to iodine, the bile duct pressure should be lower than 2.16 kPa. PMID- 1874107 TI - [Problems in the surgical treatment of gastric cancers]. AB - Radical resections were performed in 177 cases of gastric cancer (early cancer 31 cases and advanced cancer 146 cases). R+1 operation was performed in 10 cases and R2 or R3 was in 167. All patients were followed up to the end of the study with the 5-year survival rate of 57.6%. In the patients with normal serosa, cancer was often located in the mucosa. In such situation, R1 or R1+ operation was advisable. In the patients of reactive serosal types, the extent of operation should not be reduced. The serosa were often penetrated by cancer cells in diffusely infiltrated cancer, with a poor prognosis. If measures were not taken to destroy free cancer cells, the 5-year survival rate was very low inspite of radical operations. The number of lymph node metastasis was closely related to the biological behavior of primary cancer. Prognosis was good after R2 or R3 operation when the cancer was still within the gastric wall, Borrmann type 1,2,3, massive or nest growth patterns, and the number of lymph node metastasis was below 5 and within first group (n1). If the number of lymph node metastasis was above 10, metastasis to the second (n2) or third group (n3), the cancer infiltrated to the serosa, Borrmann type 4, diffused growth pattern the prognosis was poor even R2 or R3 operations were performed. PMID- 1874108 TI - [Free toe transfer with plantar metatarsal arteries and dorsal venous pedicle. Report of 18 cases]. AB - Eighteen free second toe were used for pollicization other than the conventional method. From the first and second plantar metatarsal arteries junction of the both digital arteries of the second toe were dissected retrogradely and anastomosed to the deep of superficial palmar arch or terminal branch of the radial artery. The venous return was established between the dorsal venous arch and cephalic vein. These vessels were found to have much bigger diameters and less anatomical variation than those used by conventional methods. Seventeen transplantation were considered successful both functionally and cosmetically. One cases had persistent spasmodic contraction of the recipient arteries, so the transplant was salvaged by subclavicular pedicle including the sutured nerves and the attached soft tissues as introduced by Lu in 1964. Our method for reconstruction of the thumb or finger can avoid frequent anatomical variation and smaller diameter of the anastomosed vessels. PMID- 1874109 TI - [An approach to correcting scoliosis. Mechanism and operative procedure]. AB - In the treatment of scoliosis, we found that soft tissue contracture on the concave side is the main force maintaining deformity, resisting correction and rejecting implants. So the release of contracture would get rid of the bow-string effect of the contractured tissues from the main curve, such as the capsules and ligaments around costo-transverse joints, the inter-transverse and intercostal muscles, together with the posterior section of the corresponding ribs would also be taken off by those shrunken tissues close to the main curve, like the capsules and ligaments around the costo-vertebral joints. Since 1982, 23 patients aged 6 to 16 years were treated operatively. The operation was done in 2 stages: contracture release on the concave side and fusion with bone grafting on both side laminae through body cast. Follow up for 1 to 8.5 years showed satisfactory results. The mechanism and effect of soft tissue contracture of idiopathic and congenital scoliosis are discussed in detail. PMID- 1874110 TI - [Surgical treatment of left main coronary artery stenosis]. AB - Nineteen consecutive patients with severe stenosis of the left main coronary artery underwent coronary bypass surgery between Jan. 1980 and Sept. 1989. They had typical symptoms of angina pectoris, and 10 of them showed unstable angina pattern. Disabling symptoms of angina pectoris persisted in all patients despite medication. Eight patients had myocardial infarction. Two patients (10.5%) died postoperatively. Sixteen patients (94.1%) surviving surgery were alive from 6 to 106 months after operation. 13 patients were asymptomatic, 2 had a significant reduction in angina symptoms. The findings suggest that myocardial revascularization may effectively improve the life quality and prolong life span of a patient with significantly occlusive disease of the left main coronary artery. PMID- 1874111 TI - [Diagnosis and treatment of 52 cases of cardiac myxoma]. AB - 43 patients with cardiac myxoma had undergone surgical removal of the tumors under CPB 38 tumors were located in the left atrium, 5 in right atrium, and 1 in right ventricle respectively. The sites of attachment of the tumor stalk observed during operation were as follows: 34 left atrial myxomas were attached to the interatrial septum and 4 left atrial myxomas to the atrial wall. 5 right atrial myxomas were attached to the interatrial septum and 1 right ventricular myxoma to the ventricular wall. 1 patient with a right ventricular myxoma which had been removed one year ago appeared new one in the left atrium and the tumor was cut too. The diagnosis of cardiac myxoma was confirmed by 2D-echo-cardiography in all of our cases. Mitral valve replacement was done in 1 patient in this series. There was one death postoperatively. Besides these 43 cases, there were 9 patients who had not been operated upon, because of refusal of operation in 5, sudden death from cardiac arrest before operation in 2, coma from cerebral thrombosis in 1, and serious pulmonary tuberculosis in another one respectively. PMID- 1874112 TI - [Extracorporeal shockwave lithotripsy and ureteroscopic lithotripsy for ureteral stones. A comparative study]. AB - From June 1987 to December 1988, 212 cases of ureteral calculi were treated with ESWL and ureteroscopic lithotripsy (URSL) respectively. The lithotriptic success rates of ESWL for upper, mid and distal ureteric stones were 100.0%, 100.0% and 93.4% respectively as compared with 62.5%, 85.7% and 93.7% of URSL. ESWL for upper and mid ureteral stones was obviously superior to URSL (P less than 0.001). The incidence rate of complications of ESWL was lower than that of URSL (P less than 0.05). In the 212 cases, urinary extravasation caused by ureteral injury occurred in 4 cases treated by URSL. We suggest that ESWL should be the first treatment of choice for ureteral calculi and URSL is not recommended for the treatment of upper ureteral calculi, but it may be used as an adjunctive method. PMID- 1874113 TI - [Diagnosis and treatment of adrenal cysts]. AB - Six patients with adrenal cysts, a rare disease, were treated. Among 5 patients undergoing operations, 4 had pseudocysts and one had epithelial cyst. Most of the patients had no symptoms. B-ultrasonography and CT scanning played a leading role in the diagnosis of the disease. The incidence, etiology, pathological classification and treatment of adrenal cysts are discussed. PMID- 1874114 TI - [Anaerobic infection of burns]. AB - To analyze anaerobic infection 158 specimens were obtained from deep necrotic tissues and exudates under burned subeschar, secretion of eyes and blood. The results showed that more anaerobes were isolated from deep necrotic tissues (46.88%) and smelly exudates of subeschar (38.71%). Most of them were mixed with aerobes (97.1%). In 43 strains of anaerobes, Clostridium accounted for 18 strains (41.86%), and Bacteroides for 17 strains (39.53%). Fusiform nucleatum. Peptococcus, and Veillonell paryula were also differentiated. The recent total detectable rate of anaerobes (38.71%) from burn wounds was higher significantly than that of 1980-1983 (14.7%). It may be due to the exact selection of specimens and modification of cultural medium and equipment. PMID- 1874115 TI - [Porencephaly. A report of 45 cases]. AB - In 45 cases of porencephaly 35 were male and 10 female. Their age ranged from 80 days to 58 years (mean 14 years). In this series, symptoms were observed 80 days to 22 years before diagnosis. twenty-four cases were premature delivery, difficult labour or birth trauma. 14 cases had a history of head injury. 36 cases had congenital porencephalic cyst and 9 had post-traumatic porencephaly. The main symptoms and signs of porencephaly were dementia, speech defect, intracranial hypertension, hydrocephalus, epilepsy, ataxia or paralysis. etc. It is suggested that CT scan is very useful in the diagnosis of porencephaly, and section of cerebral cortex, opening of cyst, continuous drainage or shunting operation should be done as soon as the diagnosis was made. PMID- 1874116 TI - [Neural blockage of phenol-glycerine for cancer pain]. AB - Neural blocking of phenol-glycerine was used for the treatment of cancer pain originated from the esophagus, stomach, liver, lung, rectum, ovary, nasopharynx, head and neck. According to the dose difference, 148 cases were divided into three groups of 7-10% 4-5 ml (30 cases), 15-20% 3-4 ml (70 cases), and 25% 2-2.5 ml (48 cases). The result observed among the three groups as good or fair was 46.7%, 80% and 89.6% respectively, however, complications occurred too within the rate of 13.3%, 34.3% and 14.6% respectively. It is indicated that 2.5 ml of 15 25% phenol-glycerine seems better. PMID- 1874117 TI - [Treatment of gut-derived endotoxemia with lactulose. An experimental study]. AB - Endotoxemia plays an important role in the origination and development of many dangerous clinical diseases, for which there has been little medication so far. To determine whether lactulose has an effect on endotoxemia, we treated experimental, gut-derived endotoxemia using lactulose in vitro and in vivo. The results showed that 55 mg lactulose inactivated the activity of 0.01 mg endotoxin on limulus lysate in vitro, suggesting that lactulose may have a direct anti endotoxin effect. In vivo study in rats showed that blood endotoxin level was significantly decreased from 78.61 +/- 6.54 pg/ml to 20.26 +/- 2.38 pg/ml (P less than 0.01), and liver damage significantly reduced after lactulose treatment. It is suggested that lactulose can prevent absorbtion of endotoxin from gut and may have an effect on gut-derived endotoxemia. The mechanism of lactulose for treating endotoxemia is discussed. PMID- 1874118 TI - [Internal fixation for intertrochanteric fracture. Biomechanical study]. AB - A Type IIIa intertrochanteric fracture was made on the preserved femurs of adult cadavers. The fracture was fixed by 4 methods: Percalcar Steinmann's pins, Knowle's pins, Nail plate and Angle plate. The loading limit of the fixations were 150, 140, 70 and 40 kg respectively. In fatigue test the loading ability of the percalcar Steinmann's pins were 4 times greater than that of Nail plate or Angle plate. In Nail plate and Angle plate. The pathological section of the upper femur showed the most bony destruction was at the trabecula beneath the lateral cortex, and in the percalcar Steinmann's, it was at the neck trabecula, where the cal car plays an important role in supporting the loading of the lowest pin. It was found that the level arm was shortened and the loading ability increased. As the direction of the lowest pin was nearly parallel to the loading axis of the hip. The calcar suffered less shearing force. These findings showed that the percalcar Steinmann's pins fixation is the best in these 4 methods. PMID- 1874119 TI - [Bone remodeling after internal fixation with different stiffness plates: ultrastructural investigation]. AB - Fourty adult New Zealand rabbits were used in this experiment. Four rabbits served as control and the rest 36 divided into 3 groups, each of which was fixed respectively with methylmethacrylate, titanium and strain-less steel plate on left intact tibiae. The cortical bone beneath the plate was harvested at 2, 4, 8 and 12 weeks after operation and observed by means of with transmission electron microscope. The major ultrastructural changes after internal fixation with different stiffness plates were alteration of osteocyte life cycle, perilacunar matrix, and disorder of osteoclast-osteoblast coupling. The greater the stiffness of the plate, the greater the ultrastructural change. PMID- 1874120 TI - [Oxygen free radicals and ischemic injuries]. PMID- 1874121 TI - Tetanus: pathophysiology, management, and prophylaxis. AB - As tetanus has become a rare disease in the developed world, physicians have become less comfortable with its diagnosis and management. The extent of adequate antitetanus immunity in the adult population, especially the elderly, is waning, in great measure because primary care physicians have not made prophylaxis a priority in their routine encounters with patients. Furthermore, as the population of immunocompromised hosts grows, an increasing percentage of our patients may not respond to standard active immunization routines. Unless these trends are reversed, we face a substantial increase in the incidence of this dread disorder. Tetanus is also of interest as a relatively simple model of disordered motor control that can instruct us in the management of the many more common causes of neurogenic muscular rigidity. The toxin produced by Clostridium tetani finds increasing use in laboratories investigating brain function as well. Clinical tetanus is divided into four symptomatic types: generalized tetanus, local tetanus, cephalic tetanus, and neonatal tetanus. This monograph discusses the diagnostic aspects of each type of tetanus, its pathophysiology, diagnosis, differential diagnosis, and treatment. Preventing tetanus should be a high priority for all primary care physicians. Active immunization with tetanus toxoid is remarkably effective and safe. Passive immunization with human tetanus immune globulin is indicated in certain circumstances, which are discussed below. PMID- 1874122 TI - [Malignant lymphoma associated with HIV infection]. AB - The course of disease in 119 HIV-infected patients (117 men, 2 women; median age 38.5 years) with malignant tumours other than Kaposi's sarcoma was analyzed in a multi-centre retrospective study. This was conducted to obtain initial information concerning the incidence, clinical features and results of therapy in HIV-associated neoplasms, especially malignant lymphomas. The most frequent tumour was malignant non-Hodgkin's lymphoma (98 patients, 82.5%), seven patients had Hodgkin's disease, five had solid tumours, four a polyclonal lymphoproliferative syndrome, three an acute lymphocytic leukaemia, and two had other lymphoproliferative diseases. 58% of the non-Hodgkin's lymphomas occurred in patients with marked immunodeficiency, 85% were high grade malignancies and 47% had primary extranodal disease. 56% of primary nodal lymphomas also had visceral spread (Stage IV). Lymphoblastic non-Hodgkin's lymphoma was more common in patients with favourable immunological status, presented less frequently with primary extranodal disease, was diagnosed earlier than other non-Hodgkin's lymphomas, and appeared to carry a better prognosis. 78 out of the 98 patients with non-Hodgkin's lymphoma had been treated, 66 with cytotoxics. The median survival time was 6 months. Longer remission periods, of at least 12 months, were seen in ten of the 78 patients (13%). Despite the overall poor prognosis and the pre-existing immune defect, palliative (chemo-)therapeutic measures are both justified and promising, and may also result in life-prolonging remissions. PMID- 1874123 TI - [Involvement of the central nervous system in disseminated tuberculosis]. AB - Four weeks after starting tuberculostatic treatment (with isoniazid, rifampicin, streptomycin and pyrazinamide) a 21-year-old man with pulmonary tuberculosis developed symptoms of a radiculomyelopathy as well as mild renal failure. After isoniazid and streptomycin had been discontinued and ethambutol and high doses of vitamin B6 had been added all signs and symptoms improved. However, 4 weeks later tuberculous meningitis occurred which at first seemed to respond to administration of 5 antituberculosis drugs and dexamethasone. But 3 weeks later the patient sustained a partial hemiparesis. Its cause was proven to be a tuberculoma in the region of the brainstem. During further administration of tuberculostatic drugs and glucocorticoids the symptoms gradually receded over 8 months. A 54-year-old man with pulmonary tuberculosis developed cranial nerve pareses and symptoms of cerebellar involvement (trunk ataxia, intention tremor, dysdiadochokinesia) 3 weeks after starting tuberculostatic treatment. Computed tomography revealed multiple intracerebral tuberculomas which gradually shrank with continuation of the tuberculostatic treatment plus glucocorticoids. These two case reports illustrate that in tuberculosis involvement of the CNS can express itself clinically through complex symptoms, sometimes even after the start of tuberculostatic treatment. PMID- 1874124 TI - [Diagnosis of coronary disease: current aspects]. PMID- 1874125 TI - [Self monitoring of blood sugar]. PMID- 1874126 TI - [Chologenetic diarrhea]. PMID- 1874127 TI - [Prehospital stage in acute myocardial infarct]. PMID- 1874128 TI - [Acute posttraumatic lung failure. Its treatment through pressure-limited respiration and continuous postural change]. AB - Nine patients (4 women and 5 men; mean age 31 [20-48] years) with severe posttraumatic adult respiratory distress syndrome (ARDS) were treated with continuous postural change (kinetic bed) and pressure-limited ventilation. Seven patients survived; only one patient died as a result of pulmonary insufficiency. As compliance was markedly reduced (less than 20 ml/cm H2O), low stroke volumes (up to 380 ml) and high respiratory rate (up to 45/min) were employed to keep airway peak pressure below 40 mmHg. Kinetic treatment lasted for a mean of 14 (2 28) days; artificial ventilation was maintained for 31 (9-49) days. Practical problems of the method are the intensive nursing care required for the kinetic bed and the risk of decubitus ulcers, as well as disconnection of infusion tubing. The results indicate that kinetic treatment with pressure-limited ventilation constitutes a low-risk and, in many cases, effective treatment of severe ARDS. PMID- 1874129 TI - [Immunoproliferative disease of the small intestine. A rare differential diagnosis of Crohn's disease]. AB - For 2 years a 39-year-old Turkish man had had abdominal pain as well as weight loss of more than 10 kg over 4 months, associated with a raised ESR (33 mm/h) and recurrent gastrointestinal bleedings which endoscopy revealed to have been caused by a marked erosive duodenitis. Biopsies from the duodenum and terminal ileum demonstrated lymphoplasmocytic infiltration of the entire small intestine in the sense of immunoproliferative small intestinal disease (IPSID). By immunohistochemistry the lymphoplasmacellular infiltrate showed polyclonal expression of IgA without IgA increase in serum, urine and duodenal juice. The patient was treated with tetracycline (500 mg twice daily) for one year. The symptoms and histological lesions were much improved after 4 months. One year after diagnosis he was symptom-free. PMID- 1874130 TI - [Multicystic chylous lymphangioma in the mesentery of the small intestine]. AB - In the search for metastases computed tomography and ultrasonography of the abdomen were performed in a 47-year-old man with a known malignant melanoma in the left lower leg. Numerous fluid-filled cavities, about 8 cm in diameter, were an incidental finding. He died two years after diagnosis of the melanoma, which had extensively metastasized. At autopsy a large multicystic tumour (21 x 15 x 8 cm) was found in the mesentery of the small intestine. The cysts were filled with chyle. Histologically they proved to be multicystic lymphangiomas. Mesenteric lymphangiomas are very rare, multicystic ones and manifestation in adults even more so. PMID- 1874131 TI - [Aortobronchial fistulae as late complications following the surgical correction of aortic isthmus stenosis]. AB - Three patients (2 men, aged 39 and 52 years, one woman, aged 47 years) developed hemoptysis 3-19 years after surgical resection of coarctation of the aorta. Digital subtraction angiography in the two men was suspicious of an aortobronchial fistula. An emergency thoracotomy revealed the diagnosis in the woman: she died during the operation of intractable arterial bleeding, the initial operation having been atypical (insertion of a graft extending across the isthmus to the ascending aorta). The 52-year-old man died of left heart failure after pneumonectomy (for massive bleeding into the left lung). An aneurysm sack at the aortic isthmus was resected and a vascular graft implanted in the 39-year old man. There have been no further hemoptyses. These cases emphasize the need for including aortobronchial fistula as a cause of hemoptysis. PMID- 1874132 TI - [The Hajdu-Cheney syndrome. The basilar impression as a diagnostic sign]. PMID- 1874133 TI - [The examination by employees of the notes of the occupational physician]. PMID- 1874134 TI - [Otosclerosis and estrogen-gestagen substitution in the menopause]. PMID- 1874135 TI - [A bleeding complication as a consequence of bolus lysis after resuscitation]. PMID- 1874136 TI - [The "protective acid coat" of the skin of our domestic animals]. AB - The study reviews and discusses functional aspects of the so-called "acid mantle" of the integumentum commune of domesticated mammals and birds. The problems referred to are closely related to the skin surface-pH and different factors influencing this phenomenon (chemical composition of the skin surface film, secretory activity of apocrine tubular glands, structure of the microflora, lack of skin glands in birds). It becomes evident, that an "acid mantle" of the skin of domesticated animals cannot be verified, and that normal skin-pH (medium values weakly acid to alkaline) exerts no microbicidal effects. Integumental antimicrobial properties may rather be connected with free fatty acids as decomposition products of skin lipids. PMID- 1874137 TI - [The history of the book, "The family horse doctor, or the art of healing one's own horse," by Francis Clater]. AB - Francis CLATER presumably was born in 1754 near Nottingham. He became farrier after years of apprenticeships at Newark and Retford. In 1783 the first edition of his book "Every man his own farrier" was published. Within 50 years at least 30 editions were printed. This book was translated by PRETOT into French (1822), by S. von TENNECKER (1823) and by LENTIN (1834) into German and by TURNE (1838) into Russian language. Contents of some editions are compared and valued. PMID- 1874138 TI - [The first Polish animal contagious disease act of 1844]. AB - The Veterinary Control Act of 1844 was the first to regulate in entirety the control of infectious diseases in animals and questions of sanitary inspection of animal food products in the Kingdom of Poland. The act listed explicit procedures regarding diagnostics, control and eradication of diseases as well as concerning animal food product inspection. The act required that animal owners become familiar with symptoms of animal diseases, their methods of control and that they prevent their spreading. The obligations of veterinarians, state physicians and administrative control bodies in the control of animal diseases were specified by the act. Besides the main text on the control of diseases and meat inspection the act also contains elements of food law, some norms concerning public law and order (e.g. requirements concerning dogs) and even some regulations on animal protection. PMID- 1874139 TI - [The history of the Hungarian veterinary students evacuated to the West December 1944]. PMID- 1874140 TI - Early veterinary history in the United States of America. AB - Those involved in the early history of veterinary medicine in the United States of America provided valuable services and an excellent foundation for later development of the profession. Even though the farriers and cowleeches had little knowledge, and occasionally less ethics, most performed as best they could. Certainly, the medical profession contributed greatly to the success of the American veterinary profession. Furthermore, the influence of British veterinarians and their publications added much to improving the profession. Perhaps the greatest accomplishment for the betterment of the profession was the establishment of the United States Veterinary Medical Association. Once the practicing veterinarians in the United States became organized and concerned, the profession appeared to develop rapidly providing both educational opportunities and pride in veterinary medicine. PMID- 1874141 TI - [Veterinary students in Denmark]. PMID- 1874142 TI - A survey of veterinary education and administration in Turkey. PMID- 1874143 TI - [Veterinary administration in the Rhineland--yesterday and today]. AB - The public veterinary administration was founded in July 1817 by the "Supreme Act" and developed from the public medical administration during the first half of the 19th century to finally an adequate position in 1913. In the beginning prior objectives were animal disease campaigns and participation in animal breeding activities. Towards the end of the last century the public veterinary administration also dealt with hygiene control concerning food of animal origin and meat hygiene. Further fields of activities followed, for example the control of the disposal of animal carcases, trade with animal drugs, vaccines and feedstuff, protection of animals and poultry meat hygiene. It was of special importance to the medium level of the public veterinary administration when in 1981 a chemist engaged in the supervision of food for human consumption was employed by the "Regierungsprasident" Cologne. It was then possible to lump together both control in the complete field of supervision of food for human consumption and public veterinary administration. PMID- 1874144 TI - [William Moorcroft (1767-1825). Veterinarian, explorer in Asia--and spy?]. AB - From 1790 to 1791 the surgeon William MOORCROFT studied veterinary medicine in Alford. He was the first Englishman with a complete formal veterinary education. In 1808 he gave up his horse practice and went into service of the East India Company as superintendent of the Company's Indian stud. Search for appropriate stud-horses and his efforts for opening up trading-routes from India to inner Asia induced him to exploring expeditions into the regions of the southwest Himalayas, the Hindu kush, Samarkand and Afghanistan. There he made also a lot of geographical and biological observations. He was not only one of the European pioneer Himalaya explorers but became also an early participant of the later so called "Great Game", the struggle between England and Russia for supremacy in Central Asia. PMID- 1874145 TI - [Connections between Helsinki and Hannover in the sphere of the history of veterinary medicine (short report)]. PMID- 1874146 TI - [Polish veterinary schools in the past and present]. PMID- 1874147 TI - [Deaths in swine by a lightning strike in the sty]. AB - It is reported on deaths of pigs due to lightning stroke in the barn. During a severe thunder storm 11 clinically healthy pigs with an average weight of approx. 22 kg died simultaneously and suddenly in the barn. The animals were kept on a floor of metal slats. The pens were separated by metal bars. A water pipe leading into the barn from outside had contact to the bars. Two pigs were submitted for an examination approx. three hours post mortem. The macroscopic and microscopic necropsy findings are described. PMID- 1874148 TI - The influence of colostral leukocytes on the immune system of the neonatal calf. II. Effects on passive and active immunization. AB - The influence of colostral leukocytes on the concentration of immunoglobulins and antibodies against an enterotoxigenic strain of E. coli in the sera of newborn calves was investigated for four weeks using four experimental groups. The calves received either complete colostrum (COL-, n = 16), cell-supplemented milk substitute (MS+, n = 7) or pure milk substitute (MS-, n = 6) during the first three days of life. The cows were not specifically immunized. The sera of the COL+ calves had significantly higher concentrations of antibodies against E. coli mainly of IgG1 specificity on the second day of life as compared to those of the COL-. The sera of the COL+ calves contained significantly more IgM on days 2 and 5 and slightly more IgA during the first week. Both COL groups had equal concentrations of serum IgG. It appears that colostral leukocytes which are an integral part of the colostrum enhance the passive immunity of the neonatal calf, especially in regard of antibodies and immunoglobulin classes which are essential for intestinal immunity. The concentration of IgM in the sera of the MS+ calves was reduced, that of IgG did not rise to appreciable amounts; the IgA synthesis started one week later as compared to the MS- group. The administration of isolated colostral cells led to an impairment of the natural active immunization. PMID- 1874149 TI - [Perspectives on veterinary infectious disease control in the European Economic Community]. AB - The internal market of EC from 1993 is a provocation for the veterinary services of the member states to prevent dangers by animal infectious diseases and zoonoses in a big territory without borders. The systems for the control of animal infectious diseases, transport and trade have to be adapted and the veterinary services, especially on the local basis, will have more responsibility, they will be in action more as in the past and more intensive too. Primary aim is to reach a high uniform animal health level in the whole community. This requires more burden, strong and consequent measures as till now in the concerned region or member state. The control of infectious diseases in EC will stay on three big column --uniform measures for protection against animal infectious diseases, --common system for the control within the EC, --common control system on outside borders of EC for import from third countries. The already accepted and applied principle of regionalization will get essential importance. EC will participate in financing the control of animal infectious diseases particularly of very dangerous diseases, but also in certain control- and surveillance-programs. The veterinary controls on the internal borders in EC up to now will be replaced by controls at the place of origin and the place of destination. Imports from third countries will be controlled on outside-borders of EC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874150 TI - [Double vertebral injury in a calf (case report)]. AB - A double spinal cord trauma of an eight weeks old calf is reported, born on pasture from a heifer as a premature birth at the beginning of month 9. Observations made were rupture of intervertebral disk at the crossing of cervical to thoracic vertebrae followed by syndesmosis or synchondrosis resp., as well as a comminuted fracture of the 1st lumbar vertebra including both the adjoining vertebrae, with succeeding reactive callus formation. It is concluded that this traumatization has occurred during parturition. Motoric or sensory disturbances were observed neither. PMID- 1874151 TI - [Animal nutrition for the veterinarian--recent cases. Unsatisfactory development of piglets after disintegration of a piglet breeding feed]. AB - Insufficient performance and health problems of reared piglets in individual boxes gave rise to sent 2 samples of the diet to the institute. Due to a demixing process on the transport (winding) the composition of the diet changed markedly. The crude ash content increased (62.7 g----96.2 g/kg feed), on the other hand the protein content decreased significantly (181----126 g/kg feed). Obviously the variable mineral content in the diet impaired the palatability and consequently the performance of reared piglets due to increased disposition for diarrhea. PMID- 1874152 TI - Topical ophthalmologics in otology. PMID- 1874153 TI - The Chiari-I malformation. AB - We have described the important clinical features and aspects of the Chiari-I malformations, with particular emphasis on Chiari-I malformation. Previously thought to be a rare finding with only minor significance, Chiari-I malformation is an important cause of a variety of symptoms, and will be diagnosed even more frequently as the use of MRI increases. The clinician must consider Chiari-I malformation in any patient with unexplained sensorineural hearing loss, headache, vertigo, ataxia, dysequilibrium, dysphagia or other cranial nerve symptom, especially if accompanied by more classic symptoms of this disorder, such as cervical pain or weakness. PMID- 1874154 TI - Benign osteoblastoma of the occipital bone. AB - An uncommon case of benign osteoblastoma of the occipital bone is presented. Poor vascularity of the tumor, as confirmed by the CT scan, operative and histopathological findings, was in contrast to its characteristic high vascularity. Radical resection produced an excellent result. PMID- 1874155 TI - The otolaryngic manifestations of multiple sclerosis. AB - Multiple sclerosis is a disease characterized pathologically by the disseminated demyelination of central nervous system white matter and clinically by episodes of focal neurologic deficit that occur in a relapsing and remitting course usually over many years. In most cases progressively fixed deficits occur with resultant moderate to severe disability. Symptoms and signs of multiple sclerosis are reviewed, with emphasis placed on the protean manifestations and natural history of the disease. PMID- 1874156 TI - Difficult diagnoses in pediatric otolaryngic pathology. PMID- 1874157 TI - The Physical Volume Test in impedance audiometry. AB - Impedance audiometry offers a clinically practical method for measuring the physical volume in cc of air space medial to the hermetically sealed probe tip. Knowledge of the air space volume is meaningful when average norms are known, either when the TM is intact or, more significantly, when the TM is perforated. With the latter, the temporally dynamic space changes during external, middle ear and/or mastoid disease, the size of the total air space measured offers objective information when determined over time. The resultant volume can offer an indirect mirror readout of progression or regression of a disease process. Likewise, historically there may be a close relationship between eustachian tube function and the overall air cell space within the petrotympanomastoid bone. In such conditions, the smaller the air cell space, the poorer the eustachian tube function. The PVT offers a more expedient clinical tool over roentgenography for measuring the viable air space of the middle ear and petromastoid air cell system. Since the PVT is used primarily with an open system (i.e. with a perforated TM) electroacoustic volumetric determinations with a 220 Hz acoustic input more reliably represents the actual volume present. PMID- 1874158 TI - Primary neuroblastoma of maxilla. PMID- 1874159 TI - Sinus washout resulting in pneumomediastinum. PMID- 1874160 TI - Hereditary angioneurotic edema--an often misdiagnosed entity. PMID- 1874161 TI - Memoir--the beginning of oral contraceptives. PMID- 1874162 TI - Effects of gastrin on calcium homeostasis in chickens. AB - As in the rat, gastrin and an extract of the acid-producing part of the stomach (proventriculus) were found to lower the blood Ca2+ concentration in the chicken. Furthermore, gastrin enhanced the uptake of 45Ca into the femur. It has been suggested previously that gastrin causes hypocalcemia in the rat by releasing gastrocalcin, a hypothetical hormone thought to reside in the acid-producing part of the stomach. The results of the present study in the chicken are in agreement with this concept. Not only exogenous, but also endogenous gastrin lowered blood calcium levels. Thus, the serum gastrin concentration was increased in response to ranitidine-evoked blockade of the gastric acid output; the rise in gastrin was associated with a transient drop in blood calcium. Also, food intake produced a rise in the serum gastrin concentration and a transient drop in blood calcium. However, injection of ranitidine or food intake in proventriclectomized (acid producing part of the stomach extirpated) chickens failed to lower blood calcium, supporting the view that the gastrin-evoked hypocalcemia depends upon an agent in the gastric (proventriculus) mucosa. We suggest that endogenous and exogenous gastrin evoke hypocalcemia in the chicken by the same mechanism as that which has been postulated in the rat, i.e. by mobilization of the candidate hormone gastrocalcin from endocrine cells in the acid-producing gastric mucosa. PMID- 1874163 TI - Direct and sex-specific enhancement of bone formation and calcification by sex steroids in fetal mice long bone in vitro (biochemical and morphometric study. AB - The study was carried out to examine the direct effect of the sex hormones 17 beta-estradiol (E2) and testosterone on the modeling of cultured fetal mouse long bones separated according to their sex. The culture system used allowed for the simultaneous assessment of bone growth, mineralization, and resorption on each bone. Bones from 16-day-old male and female mouse fetuses were cultured in BGJ medium, supplemented with either 10% fetal calf serum or 4 mg/ml BSA (serum-free medium) for 48 h. The bones were harvested, and their length; the length of their diaphyses; their hydroxyproline, calcium, and phosphorus contents; and their 45Ca release were measured. Histomorphometric analyses on midlongitudinal sections of bones from parallel experiments were also performed. The results indicate that in medium supplemented with 10% fetal calf serum, E2 had a dose-dependent stimulatory effect on bone formation and mineralization at 10(-7) and 10(-9) M, with no effect on bone resorption. This effect was specific to bones from female mice and to E2, since 17-alpha-estradiol had no effect. Testosterone had similar effects specific to bones from male mice, resulting in the stimulation of bone formation and mineralization at 10(-7)- and 10(-9)-M concentrations. These effects were absent when serum-free medium was used. E2 and testosterone had an anabolic effect on endochondral and periosteal bone formation and mineralization, but no effect on bone resorption. This effect is dependent on the presence of a serum factor(s). PMID- 1874164 TI - Pattern of gonadotropin-releasing hormone (GnRH) secretion leading up to ovulation in the ewe: existence of a preovulatory GnRH surge. AB - We have previously shown LH surges induced by physiological estradiol levels are invariably accompanied by robust and sustained GnRH surges in the ewe. Such an increase, however, has not been observed consistently during the preovulatory LH surge. In the present study, we examined GnRH secretion in Suffolk and Ile de France ewes during the preovulatory period using a method for pituitary portal blood collection which allows simultaneous portal and jugular blood samples to be taken at frequent intervals for up to 48 h. Ewes were sampled either during the mid-late luteal phase (n = 8) or follicular phase (n = 20). During the follicular phase, a robust increase in GnRH secretion occurred at the onset of the LH surge in 11 of 12 ewes sampled during the LH surge. The GnRH increase in most ewes was a massive surge, reaching values averaging 40-fold greater than baseline and extending well beyond the end of the preovulatory LH surge. In the single ewe not exhibiting a GnRH surge during the LH surge, postmortem inspection indicated blood was probably not sampled from the pituitary portal vessels. In the early follicular phase, GnRH-pulse frequency was greater than that observed in the luteal phase and, within the follicular phase, GnRH-pulse frequency increased further and amplitude decreased as the surge approached. These data demonstrate GnRH secretion leading up to ovulation in the ewe is dynamic, beginning with slow pulses during the luteal phase, progressing to higher frequency pulses during the follicular phase and invariably culminating in a robust surge of GnRH. The LH surge, however, ends despite continued elevation of GnRH. PMID- 1874165 TI - Growth hormone and prolactin gene expression and release in the pituitary of rainbow trout in serum-free culture. AB - The trout pituitary continuously released a large amount of GH for over a week in serum-free culture, but PRL secretion declined by day 2 in culture. The total amount of GH released during the 8 days exceeded the initial content. The pituitary content of PRL remained unchanged after 8 days of culture. The number of weakly stained GH-immunoreactive (ir) cells was increased by day 4 in culture. The GH mRNA levels in individual cells as revealed by in situ hybridization were maintained at around the same level throughout culture. In contrast, the stainability of PRL-ir cells remained unchanged during culture, although the levels of PRL mRNA decreased by day 8. Electron microscopic immunocytochemistry showed a decrease in the numbers of secretory granules and dilation of rough endoplasmic reticulum in GH-ir cells. GH synthesis, measured by incorporated [3H]leucine after GH immunoprecipitation, was elevated 120% on day 8 over day 0. The dominant control of GH and PRL secretion in rainbow trout seems to be the converse of those seen in mammals; inhibition for GH and stimulation for PRL. PMID- 1874166 TI - Radiotelemetric monitoring of hypothalamic gonadotropin-releasing hormone pulse generator activity throughout the menstrual cycle of the rhesus monkey. AB - Continuous monitoring of the electrophysiological manifestations of GnRH pulse generator activity was achieved by radiotelemetry throughout the menstrual cycles of unrestrained rhesus monkeys. The characteristic increases in hypothalamic multiunit activity (MUA volleys) associated with each LH pulse measured in the peripheral circulation were of lower frequency during the luteal phase than in the follicular phase of the cycle. Multiunit activity volley frequency increased as functional luteolysis progressed and achieved maxima of approximately one volley per hour within the first few days of the follicular phase. Unexpectedly, a dramatic decline in pulse generator frequency was observed coincidentally with the initiation of the preovulatory LH surge. Evidence is presented to support the conclusion that this deceleration of pulse generator activity is the consequence of the preovulatory rise in plasma estrogen concentration. As reported in women, a significant reduction in GnRH pulse generator frequency was observed at night during the follicular phase, but not during the luteal phase, of the menstrual cycle. PMID- 1874167 TI - Evidence for bidirectional interconversion of mammotropes and somatotropes: rapid reversion of acidophilic cell types to pregestational proportions after weaning. AB - The progression from nonpregnancy through late lactation is associated with an increase in the proportion of anterior pituitary cells that secrete PRL and a comparable decrease in the percentage of cells that release GH. These fluctuations result from variations in both the number of cells that release GH or PRL alone and mammosomatotropes, cells that release both hormones concurrently. However, it has not been determined whether this reciprocal shift in PRL and GH secretors during the onset of lactation is readily reversible. In the present study, anterior pituitaries from adult virgin, late lactating, or postweaning female rats (4, 6, or 8 days) were dispersed with trypsin and subsequently assayed for PRL and GH release using reverse hemolytic plaque assays. We found that separating lactating females from their pups for only 4 days induced a reciprocal shift in the proportions of GH and PRL cells back to levels found in virgin females. Simultaneous plaque assays were then performed to determine whether this post-weaning shift in the percentages of GH and PRL secretors was due to changes in the abundance of cells that secrete each hormone alone or in the proportion of mammosomatotropes. The overall changes in GH and PRL cell proportions consisted of variations only in the fraction of cells that secreted either GH or PRL alone; no differences were observed in the percentage of mammosomatotropes or in the overall abundance of acidophils. Our results demonstrate that the reciprocal shifts in the proportions of PRL- and GH secreting cells associated with lactation are rapidly reversible. Moreover, these results are consistent with our hypothesis that PRL and GH secretors are functionally interconvertible and further suggest that this process is bidirectional. PMID- 1874168 TI - Fluctuations in the proportions of growth hormone- and prolactin-secreting cells during the bovine estrous cycle. AB - Reverse hemolytic plaque assays were performed on monodispersed pituitary cells from cattle at various stages of the estrous cycle in an attempt to determine whether short term fluctuations in the gonadal steroid milieu influenced the proportions of pituitary cells that released GH and/or PRL. Phase of the estrous cycle was initially determined by gross ovarian morphology and later confirmed by determination of estradiol-17 beta and progesterone peripheral serum concentrations. Animals were subdivided into four groups according to phase of cycle: early luteal (EL; day 1-10), midluteal (ML; day 11-16), late luteal (LL; day 17-19), and follicular (F; day 20-21). Plaque assays demonstrated that the percentage of all pituitary cells that released PRL was greater in the EL phase than during the ML or F phases, whereas the relative abundance of GH-secreting cells remained unchanged. A more critical analysis of hormone-secreting subtypes revealed that the increase in total PRL secretors could be attributed almost exclusively to an increase in the abundance of those cells that released both GH and PRL (mammosomatotropes). Accompanying this augmentation of dual hormone secretors was a decrease in the proportion of cells that released GH alone without a change in the abundance of cells that secreted only PRL. These results strongly suggest that during the estrous cycle there is a bidirectional interconversion among cells that release only GH and mammosomatotropes. Moreover, the relationship between ratios of acidophilic subpopulations and stage of reproductive cycle indicates that ovarian steroids may regulate this phenomenon. PMID- 1874169 TI - Cytokine-mediated regulation of ovarian function: interleukin-1 inhibits gonadotropin-induced androgen biosynthesis. AB - Resident ovarian macrophages have long been recognized as potential in situ regulators of ovarian function, presumably through local paracrine secretion of regulatory molecules (i.e. cytokines). One such macrophage product, interleukin-1 (IL-1) has recently been shown to exert profound regulatory effects at the level of the ovarian granulosa cell. In this report, we examine the possibility that the adjacent theca-interstitial (androgen-producing) cell may also be a site of IL-1 reception and action. The basal accumulation of androsterone, the major androgenic steroid synthesized by whole ovarian dispersates from immature rats, in the presence of insulin (1 microgram/ml), increased 8- to 9-fold after treatment with human CG (1 ng/ml). Although IL-1 alpha or IL-1 beta (10 ng/ml) by themselves were without effect on basal androsterone accumulation, both cytokines (IL-1 beta greater than IL-1 alpha) inhibited human CG hormonal action (in the presence of insulin) in a dose-dependent manner, the maximal inhibitory effect being 75%. Similar results were obtained when using highly purified theca interstitial cells derived from the same animal model suggesting that IL-1 attenuated androgen biosynthesis is due, at least in part, to IL-1 acting directly at the level of the theca-interstitial cells. The IL-1 effect proved relatively specific since all other known interleukins (IL-1, IL-3, IL-4, IL-5, and IL-6) were without effect. Moreover, IL-1 beta action was effectively immunoneutralized when concurrently applied with anti-IL-1 beta (but not nonimmune) sera. Significantly, the antigonadotropic action of IL-1 could not be accounted for by a decrease in the viable cell mass. Tracer studies with radiolabeled steroid substrates suggested that IL-1-attenuated ovarian androsterone accumulation is due, if only in part, to inhibition of transformations catalyzed by (theca-interstitial) 17 alpha-hydroxylase/17:20 lyase, stimulation of theca-interstitial (or granulosa 20 alpha-hydroxysteroid dehydrogenase-mediated conversions, or both. Taken together, these findings indicate that relatively low concentrations of IL-1, possibly originating from somatic ovarian cells or resident ovarian macrophages, are capable of exerting an inhibitory effect upon gonadotropin-supported androgen production. As such, these and previous observations suggest that intraovarian IL-1 may play a dual regulatory role in the developing ovarian follicle by targeting both the granulosa and theca-interstitial cells as its sites of action. PMID- 1874170 TI - Purification and characterization of mouse decidual calcyclin: a novel stimulator of mouse placental lactogen-II secretion. AB - The effects of secretagogue(s) from mouse decidual tissue on the release of mouse placental lactogen-II (mPL-II) were studied. Decidual tissue was obtained from 10 and 11-day-pregnant mice. The tissue was homogenized, extracted, and the tissue extract was made 50% saturated with ammonium sulfate. Both the precipitate and supernatant were tested for their ability to stimulate mPL-II release from cultured trophoblasts. The supernatant contained an activity to stimulate the release of mPL-II. This activity was further purified using column chromatography. The purification resulted in isolation of a protein with a mol wt of 20 K as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions and 6 K under reducing conditions. Further characterization of this protein showed that it binds calcium and has an amino acid sequence that is highly homologous with calcyclin expressed in mouse embryonic fibroblast cells and with calcyclin from other species. This protein was designated mouse decidual calcyclin. Antiserum was raised against the purified decidual calcyclin for development of an RIA and for immunoblots. Western blots of various mouse tissue extracts and mouse serum from different physiological stages showed that the concentration of calcyclin was highest in decidual tissue. Detectable levels were found in extracts from trophoblast, lung, and stomach, but the concentrations in these tissues were about 100 times lower than in decidua. Decidual calcyclin was not detectable in mouse serum. Cultured decidual cells released calcyclin into the medium. On average, this release was about 7.8 ng/micrograms DNA.24 h. The rate of release did not change significantly during 4 days of culture. The ratio of calcyclin in cells per calcyclin released during 24 h averaged 2.3 and did not change significantly during the culture period. The purified decidual calcyclin stimulated the release of mPL-II from cultured trophoblasts in a dose-dependent manner at concentrations from 0.01 to 1 microgram/ml. The maximum stimulation averaged about 1.5 times above control. It is concluded that decidual calcyclin may be of physiological importance for the regulation of mPL-II secretion. PMID- 1874171 TI - Primary structure and biological activity of human brain-derived neurotrophic factor. AB - Brain-derived neurotrophic factor (BDNF) is a 27-kDa basic protein of noncovalently linked 13.5-kD subunits related to nerve growth factor and is produced by the central nervous system (CNS). BDNF has been shown to promote the survival of neurons located in or directly connected with the CNS and is likely to function in adjusting the cell number within neuronal populations to the need of this projection field. Here we describe the primary structure of a human BDNF cDNA, the biological activities of pure recombinant human BDNF, and the tissue distribution of rat BDNF. BDNF mRNA can be found in some peripheral tissues as well as in the CNS, and recombinant human BDNF is a potent neurotrophic factor for primary peripheral sensory neurons. PMID- 1874172 TI - Regulation of ovarian steroid biosynthesis by estrogen during proestrus in the rat. AB - Studies were performed to test the hypothesis that the rapid decline in estradiol (E2) levels on proestrus before ovulation was due to a reduction in androgen substrate for aromatase, and that this decline in androgen was regulated by an estrogen receptor-mediated mechanism. Aromatase activity, concentrations of E2, androstenedione (A), testosterone (T), and progesterone (P4) in follicular, corpora lutea, and ovarian homogenates as well as peripheral E2, A, P4, and LH were measured in cycling rats from 1400-2000 h on proestrus. These parameters were also recorded after the expected E2 surge in animals treated at 1900 h on diestrous day 2 with the antiestrogen keoxifene (20 mg/kg), with or without an ovulatory dose of PMSG at 1600 h on proestrus. In a second experiment, P-450-17 alpha-hydroxylase/C17,20-lyase (P-450(17 alpha] activity was measured in a group of control rats at 1500, 1700, and 1900 h. Aromatase activity remained unchanged, even though serum and ovarian E2 levels were reduced from peak values at 1500 h to basal values at 1800 h (P less than 0.01). Peripheral A as well as ovarian androgens (specifically follicular but not luteal) A and T were also reduced over this time period (P less than 0.01). Although total ovarian P4 remained unchanged, follicular levels rose from 1400-2000 h (P less than 0.01). These reductions in androgens and E2 levels coincided with a marked reduction in follicular P-450(17 alpha) activity. Treatment with keoxifene with or without PMSG prevented the fall in peripheral E2 and A and the increase in peripheral P4 seen in controls. Ovarian and follicular E2, A, and to a lesser extent T were also remained at values similar to those during the E2 surge. Follicular P4 was reduced by both treatments. Neither treatment had any effect on aromatase. These results indicate that the fall in peripheral and ovarian E2 levels before ovulation was due to a decline in aromatizable androgen, through an inhibition of follicular P-450(17 alpha) enzyme activity, which appears to be mediated by an estrogen receptor-regulated mechanism. PMID- 1874173 TI - Interleukin-1 inhibits cholesterol side-chain cleavage cytochrome P450 expression in primary cultures of Leydig cells. AB - Interleukin-1 (IL-1) is a potent inhibitor of Leydig cell function. We have reported that IL-1 inhibited hCG-induced cAMP and testosterone formation. In the present study we evaluated the effect of IL-1 on Leydig cell cholesterol side chain cleavage cytochrome P450 (P450scc) mRNA levels. P450scc is the rate limiting enzyme for Leydig cell steroidogenesis. Highly purified Leydig cells were prepared from adult Sprague-Dawley male rats (55-65 day-old) using the combination of elutriation and Percoll gradient. Purified Leydig cells were then cultured with or without IL-1 beta (1-100 ng/ml) and recombinant human monocyte derived IL-1 receptor antagonist (250 ng/ml) for 24 h. hCG (10 ng/ml), 8-bromo cAMP (0.1 mM), or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate was then added, and cultures were continued for an additional 6 h. P450scc mRNA levels of Leydig cells were very low to undetectable after 24 h in culture and could be stimulated by the addition of either hCG (10 ng/ml) or 8-bromo-cAMP (0.1 mM), but the addition of 4 beta-phorbol 12 beta-myristate 13 alpha-acetate had no effect. P450scc mRNA levels increased as early as 2 h after the addition of hCG. Furthermore, cycloheximide (1 microgram/ml) markedly blocked hCG-induced P450scc mRNA expression. This indicates that synthesis of a labile new protein(s) is required for the induction of P450scc mRNA by hCG. IL-1 beta inhibited hCG stimulated testosterone formation and P450scc mRNA expression in a dose-dependent manner. The inhibitory effects of IL-1 beta could be reversed by the concomitant addition of IL-1 receptor antagonist. Our results suggest that P450scc mRNA levels of Leydig cells are modulated by IL-1. This may be one mechanism that could explain the inhibitory effects of IL-1 on Leydig cell steroidogenesis. PMID- 1874174 TI - Immunodetection of estrogen receptors in fetal and neonatal female mouse reproductive tracts. AB - An immunocytochemical assay for estrogen receptor (ER) was used to study the distribution of receptor in fetal and immature female mouse reproductive tracts. Immunoblots confirmed that a single band, the size of the ER, immunostained in extracts from day 15 and 17 fetal reproductive tracts. Staining was observed over nuclei of epithelial cells of the Mullerian duct and over nuclei of cells of the developing connective tissue (mesenchymal cells) of the reproductive tract on fetal day 15. By day 17 when a primitive uterus could be distinguished, ERs were detected in nuclei of mesenchymal cells, but in only a small portion of epithelial cells. A different pattern of immunocytochemical staining was observed in uteri from animals killed on the day of birth; cells of the connective tissue contained ER, but the epithelial cells did not. By 4 or 6 days after birth, more nuclei in the connective tissue stained for ER with a greater intensity compared to nuclear staining in epithelial cells. ERs were detectable in nuclei of both uterine epithelial cells and connective tissue cells on days 10 and 19 after birth. PMID- 1874175 TI - Modulatory effects of unsaturated fatty acids on the binding of glucocorticoids to rat liver glucocorticoid receptors. AB - Binding of the synthetic glucocorticoid dexamethasone to the rat liver cytosol glucocorticoid receptor was inhibited by physiological concentrations of nonesterified fatty acids as a function of increasing dose, degree of unsaturation, and chain length of the fatty acid. Polyunsaturated fatty acids were the most potent inhibitors. Scatchard analysis and Line-weaver-Burk plots of the binding data revealed that both the association constants and number of binding sites decreased and that polyunsaturated fatty acids inhibition was of a mixed non-competitive type. The dissociation rate constant of [3H]dexamethasone from glucocorticoid receptors was increased by up to 10 times in the presence of docosahexaenoic acid, whereas a competitive inhibitor like the glucocorticoid antagonist RU 38486 had no effect. Moreover, sucrose density gradient analysis showed that docosahexaenoic acid inhibited the binding of [3H] dexamethasone to both the 8.8S and 4S forms. The results strongly suggest that unsaturated fatty acids are interacting at a site on the receptor different from the hormone binding site and the heat shock protein and that by binding to a second site unsaturated fatty acids greatly change the conformation of the hormone binding site to reduce its affinity for the hormone, either partially or completely depending on the concentration and the class of the fatty acid. PMID- 1874176 TI - Quinone reductase enzyme activity in pancreatic islets. AB - A water-soluble quinone, coenzyme Q0 (CoQ0), was shown to stimulate insulin release, and dicumarol, an inhibitor of quinone reductase, inhibited glucose induced insulin release in pancreatic islets. Since this suggested that quinone reductase might play some role in physiological insulin release, this enzyme was characterized in islets. More than 90% of the total activity was located in the cytosol, but the specific enzyme activity was highest in the microsomal fraction. The relative rates of activity with various substrates (CoQ0 approximately equal to durohydroquinone greater than menadione greater than duroquinone greater than CoQ6 = CoQ10 greater than ferricyanide) were similar to those described previously for quinone reductase from liver Dicumarol, chlorpromazine, and T3 were much more potent inhibitors of the enzyme when NADPH was the coenzyme than when NADH was the coenzyme. Dicumarol was the most potent inhibitor. The enzyme was not inhibited by rotenone. Islets ranked second to liver in quinone reductase activity, but the activity in islets was much closer to that found in all other tissues examined. Quinone reductase may play a role in insulin secretion. PMID- 1874177 TI - Deiodination of iodothyronine sulfamates by type I iodothyronine deiodinase of rat liver. AB - The substrate behavior of synthetic N-sulfonated iodothyronines (iodothyronine sulfamates, TiNS) for the type I deiodinase was compared with that of the naturally occurring 4'-O-sulfonated iodothyronines (iodothyronine sulfates, TiS), which have been shown to be deiodinated 40-200 times more efficiently than the native iodothyronines. Deiodination was studied in incubations of rat liver microsomes with unlabeled or 3' (5')-125I-labeled T4NS, rT3NS, T3NS, and 3,3' T2NS at 37 C and pH 7.2 in the presence of 5 mM dithiothreitol. Reaction products were analyzed by RIA or Sephadex LH-20 and HPLC. Kinetic studies were performed under initial reaction rate conditions to determine the apparent Michaelis Menten (Km) constants and maximum velocity values. In contrast to T4S, which is converted only by inner ring deiodination (IRD), T4NS underwent both IRD and outer ring deiodination (ORD), similar to T4, but more rapidly. At 10 nM T4NS substrate, T3NS was the major product observed, while no rT3NS accumulated due to its rapid conversion to 3,3'-T2NS. At least one third of the 3,3'-T2NS was converted by IRD, unlike 3,3'-T2 which is a pure ORD substrate. The type I deiodination efficiencies of T4NS IRD and ORD were 17-fold higher than with T4, mainly due to approximately 32-fold lower apparent Km values. Deiodination of rT3, the preferred type I substrate, was not improved by sulfamation. T3NS and 3,3'-T2NS were deiodinated 4-10 times more efficiently than T3 and 3,3'-T2, respectively, due to 2- to 4-fold decreases in apparent Km values with a concomitant doubling of maximum velocity values. N-Sulfonation stimulates type I deiodination to a similar extent as other side-chain modifications that eliminate the positive charge of the nitrogen (e.g. iodothyroacetic acids). However, the effects are less dramatic than those induced by 4'-sulfation with respect to both efficiency and specificity of the catalytic process. PMID- 1874178 TI - Influence of castration, alone or combined with thymectomy, on the development of diabetes in the nonobese diabetic mouse. AB - The nonobese diabetic (NOD) mouse is a recognized model for studying immunologically-mediated insulin-dependent diabetes mellitus. The disease appears with a greater preponderance in females than in males. Castration at weaning led to a significant increase in the prevalence of diabetes in NOD males, whereas a tendency to a decreased prevalence was observed in NOD females. Castration combined with thymectomy was found to further increase the prevalence of diabetes in NOD males, whereas in females castration reversed the effect of thymectomy. These results on changes in diabetes prevalence were corroborated by the degree of lymphocytic infiltration directed toward the pancreatic islets of Langerhans. Taken together these results indicate a direct relationship between the endocrine and immune systems, whereby orchidectomy has a deleterious effect on the immunopathogenesis of diabetes. In addition, we examined whether the distribution of lymphocyte subpopulations, mitogen reactivity, lymphokine production, and in vivo response to a thymus-dependent antigen, such as sheer red blood cell, were dependent or independent of the sex steroid environment. PMID- 1874179 TI - Functional antagonism between endogenous mouse growth hormone (GH) and a GH analog results in dwarf transgenic mice. AB - A dwarf transgenic mouse (DTM) line has been established in which mice express relatively high levels of a mutated bovine (b) GH gene. This bGH analog binds to mouse liver membrane preparations with an affinity similar to that of wild-type bGH. The mean growth ratio of these mice is approximately 0.7 relative to that of their nontransgenic littermates. Serum insulin-like growth factor-I (IGF-I) levels of DTM were found to be approximately half those in nontransgenic littermates. Liver GH receptor levels were up-regulated in DTM or wild-type bGH transgenic mice. Pituitary GH levels were negatively correlated with serum IGF-I concentrations. Wild-type bGH transgenic mice contain relatively high serum IGF-I and low pituitary GH levels, whereas DTM possess low serum IGF-I and high pituitary GH levels. The decrease in serum IGF-I resulting from the interaction between the bGH analog, the endogenous mouse GH, and GH receptor(s) apparently leads to a dwarf phenotype. These data suggest that this bGH analog has uncoupled GH ligand-receptor binding from IGF-I production and acts as a functional antagonist to the action of endogenous mGH. PMID- 1874180 TI - Pituitary regulation of postnatal small intestinal ontogeny in the rat: differential regulation of digestive hydrolase maturation by thyroxine and growth hormone. AB - During the third week of postnatal life, dramatic ontogenic changes occur in the morphology and enzymology of the small intestine of the infant rat, enabling the animal to make the transition from milk to solid food. To investigate the roles of T4 and GH in regulation of these changes, infant rats were hypophysectomized on day 6 of life by the transauricular technique. Hypophysectomy resulted in diminution of somatic and intestinal growth as well as abnormal maturation of the disaccharidases lactase, sucrase, and maltase when measured on day 25. Administration of either T4 or GH to hypophysectomized animals resulted in moderately increased intestinal growth, while complete restoration of small intestinal growth resulted from administration of the combination of both hormones. Although T4, GH, or the combination of hormones reduced lactase activities, T4 alone produced normal maturation of sucrase and maltase. Neither hypophysectomy nor hormone replacement affected aminooligopeptidase. The molecular structure of lactase, analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was not altered to a major degree in hypophysectomized animals or animals that received hormone replacement, but minor alterations were evident in sucrase structure in hypophysectomy. These studies indicate that 1) T4 and GH actively participate in postnatal regulation of small intestinal ontogeny; 2) thyroid hormones act directly on developing intestinal tissues to independently produce the normal maturation of the disaccharidases by mechanisms that are not likely to involve alterations in processing of the enzyme-protein; and 3) maturation of aminooligopeptidase is not regulated by pituitary hormones, in distinct contrast to the disaccharidases. PMID- 1874181 TI - Multiple mechanisms for regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5 ---delta 4-isomerase, 17 alpha-hydroxylase/C17-20 lyase cytochrome P450, and cholesterol side-chain cleavage cytochrome P450 messenger ribonucleic acid levels in primary cultures of mouse Leydig cells. AB - The regulation of mRNA levels for delta 5-3 beta-hydroxysteroid dehydrogenase/delta 5----delta 4-isomerase (3 beta HSD), 17 alpha-hydroxylase/C17 20 lyase cytochrome P450 (P450(17 alpha] and cholesterol side-chain cleavage cytochrome P450 (P450scc) was studied in primary cultures of mouse Leydig cells. Treatment of Leydig cells with 8-bromo-cAMP (cAMP) was essential for expression of P450(17 alpha) mRNA, but not for 3 beta HSD. Treatment with cAMP caused a decrease in basal levels of 3 beta HSD mRNA. The addition of aminoglutethimide (AG), an inhibitor of cholesterol metabolism, to the cAMP-treated cultures resulted in increased expression of both 3 beta HSD and P450(17 alpha) mRNA levels. The addition of testosterone or the androgen agonist mibolerone to cAMP- plus AG-treated cultures reduced 3 beta HSD and P450(17 alpha) mRNA to levels comparable to those observed when cells were treated with cAMP only. The glucocorticoid dexamethasone reduced both basal and cAMP- plus AG-induced increases in 3 beta HSD mRNA, but not in P450(17 alpha) mRNA. Estradiol at a concentration of 1 microM had no effect on cAMP- plus AG-induced 3 beta HSD or P450(17 alpha) mRNA levels. The role of protein synthesis in mediating the cAMP induction of 3 beta HSD, P450(17 alpha), and P450scc was investigated. The addition of cycloheximide (10 micrograms/ml) to cAMP-treated cultures for 24 h completely suppressed both constitutive and cAMP-induced 3 beta HSD mRNA levels. Cycloheximide also repressed cAMP-induced levels of P450(17 alpha) to 12% of levels observed in the absence of cycloheximide. In sharp contrast, 24-h treatment with cycloheximide did not suppress cAMP induction of P450scc mRNA, but reduced basal levels by approximately 50%. A time course of induction by cAMP (50 microM) of P450(17 alpha) and P450scc mRNA showed very similar rates of increase in P450(17 alpha) and P450scc mRNA, with the greatest increase occurring between 12 and 24 h of treatment. The results of the study demonstrate that in normal mouse Leydig cells steady state levels of mRNA for 3 beta HSD, P450(17 alpha), and P450scc are differentially regulated. cAMP is required for maximal levels of all three mRNAs. There is high constitutive expression of 3 beta HSD and P450scc mRNA, while expression of P450(17 alpha) mRNA is absolutely dependent on cAMP stimulation. Endogenously produced testosterone negatively regulates the expression of cAMP-induced P450(17 alpha) and 3 beta HSD, while the glucocorticoid dexamethasone negatively regulates 3 beta HSD and P450scc.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1874182 TI - Control of gonadotropin secretion in the ovine fetus. IV. Male-specific entrainment of the hypothalamic control of luteinizing hormone secretion by testosterone in the female ovine fetus. AB - The role of testosterone (T) in the sex-specific entrainment of hypothalamic LH regulation was studied in five castrate and four sham-castrate chronically catheterized female fetuses androgenized by the prior administration of T cypionate (200 mg, im, every 2 weeks) to pregnant ewes from 30-86 days gestation (term = 147 days). Eight female and three male castrate fetuses served as controls. After a 2-week washout period all fetuses were operated upon in utero between 106-116 days and were studied longitudinally over a 2- to 35-day period. LH pulsatility was determined from blood samples obtained every 15 min over a standard 3-h observation period and assayed for LH by RIA (NIH LH-S16 standard). LH pulse frequency in the castrate androgenized females (41 pulses in 19 observation periods; 1 pulse/1.4 h) was significantly higher than that in non androgenized female controls (18 pulses in 28 observation periods; 1 pulse/4.7 h observation), but was similar to that in castrate males (23 pulses in 28 observation periods; 1 pulse/1.3 h). Furthermore, LH pulse frequency in the sham castrate androgenized females (26 pulses in 13 observation periods; 1 pulse/1.5 h) was comparable to that in castrate androgenized females as well as that in castrate males. The enhanced LH pulsatility in androgenized female fetuses strongly suggests that T exposure between 30-86 days results in male-specific entrainment of hypothalamic LH regulation. Moreover, the comparable enhancement of LH pulse frequency in both sham castrate and castrate androgenized female groups suggests that in the T-exposed fetus T withdrawal alone is sufficient to result in enhanced LH pulsatility. These findings strongly suggest that T of fetal testicular origin results in male-specific entrainment of hypothalamic function and may be an important feature of male neural organization in this species. PMID- 1874183 TI - Thrombin and parathyroid hormone mobilize intracellular calcium in rat osteosarcoma cells by distinct pathways. AB - The mechanisms by which PTH and thrombin mobilize intracellular Ca2+ (Cai2+) were examined in UMR 106-H5 rat osteosarcoma cells. Bovine PTH-(1-34) (24 pM to 240 nM) produced a dose-dependent increase in Cai2+ (EC50, 3 nM), which returned to baseline within 75 sec. Human alpha-thrombin produced an increase in Cai2+ (ECmax, 10 U/ml) which was similar to that of PTH with respect to both magnitude and time course. Chelation of extracellular calcium with 5.0 mM EGTA did not alter the Cai2+ response to either PTH or thrombin. When added together at maximally effective concentrations, PTH and thrombin produced additive effects on Cai2+ in the presence and absence of EGTA. The additive effects of PTH and thrombin on Cai2+ were confirmed at the single cell level, using laser-based image analysis. Bradykinin (1 microM) produced a significant increase in Cai2+ in UMR 106-H5 cells which was of lesser magnitude than the peak 2- to 3-fold increase elicited by PTH or thrombin. Preexposure of cells to 10 U/ml thrombin for 2 min abolished the Cai2+ response to bradykinin, whereas preexposure to 240 nM PTH had no effect on the Cai2+ response to bradykinin. Thrombin elicited a rapid increase in the accumulation of 3H-labeled inositol phosphates (IP2 and IP3) in UMR 106-H5 cells, with increases in [3H]1,4,5-IP3 detectable as early as 15 sec after the addition of thrombin. Bradykinin increased [3H]IP production to a lesser extent than thrombin, whereas PTH neither increased [3H]IP accumulation nor potentiated the [3H]IP response to thrombin. The results suggest that thrombin and bradykinin mobilize Cai2+ from a shared IP3-responsive calcium pool, whereas PTH may use signals in addition to 1,4,5-IP3 to mobilize calcium from a distinct cellular calcium pool. Alternatively, specific calcium compartmentalization exists, and there is differential coupling of these agonists to the 1,4,5-IP3/Cai2+ pathway. PMID- 1874184 TI - A physiological role for sporadic interruptions of the dopaminergic tone in the genesis of big mass prolactin pulses. AB - The present studies were designed to evaluate pulsatile PRL secretion after the establishment of either a continuous dopaminergic input or a complete blockade of the dopaminergic inhibitory tone. Adult female rats on estrus and male rats implanted with indwelling jugular cannulae were bled at 3-min intervals for a 3-h period. Bromocriptine (CB-154) and domperidone (DOM) were administered sc and iv, respectively. The administration protocol used for both treatments produced either a continuous dopaminergic input (CB-154 treatment) or a complete dopaminergic blockade (DOM treatment). Pulse analysis was performed on the data series using the algorithm Detect. In both estrous female and male rats, dopaminergic receptor activation by CB-154 reduced peak and trough values, pulse amplitude, area under the pulse, and mean PRL levels. In contrast, a complete dopamine (DA) receptor blockade by DOM increased these parameters. Domperidone treatment increased pulse frequency and reduced pulse interval and duration. Bromocriptine, however, differentially affected some pulsatility parameters depending on the sex of the rats. In females, CB-154 did not alter any of the qualitative parameters (frequency, pulse interval, and duration) of pulsatile PRL secretion. In contrast, in male rats the treatment reduced frequency and duration while increasing pulse interval. CB-154 reduced basal PRL levels in male rats, whereas in estrous females this parameter was not altered. PRL pulses were further evaluated by frequency distribution analysis, using the area under the pulses divided by the baseline to normalize the data due to treatment-induced differences in baselines. This calculation allows the estimation of the amount of hormone released per pulse over the baseline. In both estrous female and male rats, two classes of PRL pulses were identified. One class corresponded to pulses containing a small mass of hormone [small mass pulses (SM)], while the others were characterized by pulses containing a large mass of hormone [big mass pulses (BM)]. Interestingly, both the dopaminergic agonist CB-154 and the dopaminergic antagonist DOM dramatically diminished BM pulse incidence in both estrous female and male rats. In fact, BM pulses were practically absent in both experimental groups. To further substantiate this notion, animals of each experimental group were assigned to one of the following categories: animals depicting BM and SM pulses or rats presenting solely SM pulses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1874185 TI - Uptake and ultrastructural localization of a [125I] growth hormone releasing factor agonist in male rat pituitary gland: evidence for internalization. AB - GRF was isolated from a human tumor of the pancreas and characterized. GRF stimulates the in vivo and in vitro secretion of GH. The present study was designed to find out whether human (h) GRF agonist could be internalized and to determine the subcellular localization of internalized peptide in somatotrophs. Autoradiography was performed on rat anterior pituitary glands removed at specific time intervals (2-60 min) after iv injection of monoradioiodinated [125I] (His1,Nle27) hGRF (1-32) NH2. Administration of an excess of unlabeled hGRF agonist along with the radioiodinated hormone prevented the uptake, indicating the specificity of the reaction. At the ultrastructural level only the somatotrophs appeared to contain silver grains. The main effect of hGRF agonist injection on the cytological aspect of the somatotrophs was a decrease in the area occupied by secretory granules, accompanied inversely, by an increase in that of the Golgi complex. The time course study in somatotrophs showed that five compartments (plasma membrane, secretory granules, cytoplasmic matrix, nuclear membrane, and lysosomes) have distinct marked labeling patterns. Plasma membrane, secretory granules, and nuclear membrane were labeled throughout the time course studied (2-60 min after injection). Cytoplasmic matrix was labeled 5 min post injection and lysosomes 15 and 30 min after injection. The Golgi complex, mitochondria, rough endoplasmic reticulum, and nucleus matrix were not labeled. The findings show the cellular specificity of GRF uptake by somatotrophs and the internalization process from the plasma membrane to the intracellular organelles (secretory granules, lysosomes, and nuclear membrane). Labeling of the secretory granule compartment suggests that granules may bind and protect internalized peptide from lysosomal degradation. The appearance of label on the nuclear membrane suggests that GRF may have effects on the translocation of messenger RNA from nucleus to cytoplasm in somatotrophs. PMID- 1874186 TI - Developmental regulation of the distribution of rat brain insulin-insensitive (Glut 1) glucose transporter. AB - We examined the immunohistochemical localization of Glut 1 in sections of developing rat brain [gestational (G) days 18 and 20, postnatal (P) days 1, 10, 21, and greater than 40; term = approximately G21] and characterized the abundance of Glut 1 in isolated brain microvessels by Western blot analysis. Further quantitation of total glucose transporters by [125I]3-iodo-4-azido phenethyl-amido-7-O-succinyldeacetyl-forskoli n photoaffinity labeling was performed. Glut 1 was prominently distributed in G18 and P1 brain vascular endothelial cells, with comparatively little immunoreactivity observed in brain parenchyma. Conversely, at P10, Glut 1 was prominent in brain parenchyma (undifferentiated cells) and less evident in the vascular endothelium. However, at P21, a resurgence of Glut 1 in vascular endothelial cells was observed, as was a sustained presence in parenchymal cells. On P greater than 40, a distribution in vascular endothelial cells and, to a minor extent, in parenchymal perivascular stellate cells was noted. Microvessel preparation Glut 1 (approximately 55-60 kDa) and [125I] 3-iodo-4-azido-phenethyl-amido-7-O-succinyldeacetyl-forskolin photoaffinity-labeled glucose transporters gradually increased from G18 through P10 to P greater than 40. This developmental increase in Glut 1 was also seen in whole homogenates (approximately 45-47 kDa), but not in crude brain membranes. Thus, isolated microvascular preparations indicated that Glut 1 levels constantly increased with maturation, but direct visualization of brain sections revealed that the localization in different cellular compartments changed with development. These alterations in cellular localization of glucose transporters, appear to occur in concert with the changing glucose metabolic needs of the brain, which, during the various stages of development, exhibits constantly changing phases of cellular growth and proliferation. PMID- 1874187 TI - The heterogeneity of human chorionic gonadotropin (hCG). I. Characterization of peptide heterogeneity in 13 individual preparations of hCG. AB - Peptide variations in the alpha-subunit (molecules starting at alpha 3 and alpha 4) and beta-subunit (missing linkages at beta 44-45 and beta 47-48) of hCG have been reported by several investigators. Studies, however, have been limited to standard hCG preparations (purified from large pools of urine) and other hCG samples from mixed urines. In this study we used chromatographic procedures to purify the total hCG content of 13 individual urines, 6 from patients with pregnancy and 7 from those with trophoblast disease (no hCG-containing fractions were excluded). Then, we examined for the first time the peptide variability among individual samples of hCG. We report 1) that individual hCG preparations have nicks (missing linkages) in the beta-subunit, primarily between residue 47 48 (11 of 13 samples) and, less commonly, at the linkage 44-45 or 46-47 (3 of 13 samples); 2) the extent of nicking varies greatly between individual preparations (range, 0-100% of molecules); 3) varying alpha-subunit N-terminal heterogeneity (N-terminus starting at alpha 3 or alpha 4) was also present (range, 0-28% of molecules), but was confined to preparations from individuals with trophoblast disease (6 of 7 samples from trophoblast disease urine, 0 of 6 from pregnancy urine); 4) hCG missing the beta-subunit C-terminal region was also detected (2 of 13 hCG preparations); and 5) 1 of 13 preparations was nicked on the hCG alpha subunit, between residues 70 and 71. Thus, 12 of 13 individual hCG samples demonstrated at least 1 of 4 different forms of peptide heterogeneity. We conclude that individual hCG samples vary widely in the type and extent of peptide heterogeneity, an observation that is not appreciated when pools of hCG are studied. PMID- 1874188 TI - Dose-dependent effects of tamoxifen on long bones in growing rats: influence of ovarian status. AB - Tamoxifen is a nonsteroidal antiestrogen which has been reported by various investigators to have estrogen agonist and antagonist effects on rat bone. These different interpretations may be due to differences in the ovarian status, estrogen levels, and/or tamoxifen levels of the rats. To address this issue, a dose response was determined for the effects of tamoxifen on bone histomorphometry in intact female and ovariectomized (OVX) rats. The results were compared with those obtained after treatment of OVX rats with estrogen alone or a combination of estrogen and tamoxifen. OVX resulted in increases in growth rate (weight gain) and periosteal bone formation rate and decreases in uterine weight and cancellous bone fractional volume (BV/TV). Treatment of OVX rats with estrogen resulted in dose-dependent decreases in growth rate and periosteal bone formation rate as well as dose-dependent increases in uterine weight and BV/TV. Similarly, tamoxifen treatment resulted in dose-dependent decreases in overall growth rate and periosteal bone formation rate in both OVX and intact rats. Tamoxifen treatment prevented the decrease in BV/TV after OVX, although the highest dose of tamoxifen resulted in a small decrease in BV/TV in intact female rats. In contrast to estrogen, tamoxifen treatment prevented the increase in uterine weight in intact female rats as well as the decrease in uterine weight in OVX rats. Tamoxifen treatment did not alter the effects of 17 beta-estradiol on the periosteal bone formation rate in OVX rats, but reduced the increase in BV/TV to values similar to those in intact rats. These results are consistent with tamoxifen behaving as a partial estrogen agonist on rat bone. PMID- 1874189 TI - Morphological characterization of immortalized hypothalamic neurons synthesizing luteinizing hormone-releasing hormone. AB - An immortalized LHRH cell line has recently been developed by genetically targeting these neurons for tumorigenesis. One of the subclones, the GT1-7 cells, was characterized at both the light and electron microscopic levels to study the cellular and subcellular organization of these cells, particularly as they relate to biosynthesis, processing, and secretion. The cells were fixed onto slides 18 36 h after plating. LHRH and GnRH-associated peptide (GAP) immunoreactivities (IR) were detected by immunocytochemistry using colloidal gold labeling. These cultured cells exhibited the classical neuronal appearance of LHRH neurons, and they established numerous interconnections. Neighboring neurons were coupled by tight junctions, while more distant cells were interconnected with neural axon like processes and collaterals. This cellular organization is suggestive of a neural network where neuronal activity is coordinated. At the ultrastructural level, the nondividing cells possessed indented nuclei, well developed Golgi complexes, and abundant numbers of ribosomes and secretory granules. Clathrin coated vesicles were found in fusion with the plasma membrane. The ribosomes and secretory vesicles were particularly prominent, suggestive of high rates of protein biosynthesis and secretion. All of the cells immunostained for both LHRH and GAP; however, GAP IR was always more pronounced than that for LHRH. This finding was corroborated by biochemical data reported in a companion paper. The GAP IR was associated with ribosomes and secretory vesicles. By comparison, LHRH IR was restricted mainly to the secretory vesicles. Using colloidal gold particles of different sizes to denote LHRH or GAP IR, it was determined that both GAP and LHRH IR were colocalized within the same secretory vesicle. Taken together, these data suggest that pro-LHRH is biosynthesized on the ribosomes, packaged as an intact protein into the secretory vesicles, processed to LHRH and GAP-(1-56) within these vesicles, and transported to the periphery of the cell in preparation for secretion. These morphological data emphasize the utility of using these immortalized LHRH neuronal cells to dissect the cellular and subcellular architecture involved in biosynthesis, processing, and secretion. In addition, our results provide the first detailed evidence for the intracellular pathway involved in pro-LHRH biosynthesis, processing, and secretion in these cultured neuronal cells. PMID- 1874190 TI - Two distinct effects of recombinant human tumor necrosis factor-alpha on osteoclast development and subsequent resorption of mineralized matrix. AB - The multifunctional cytokine tumor necrosis factor-alpha (TNF alpha) stimulates osteoclastic resorption. It is not known which steps in osteoclast formation are affected by TNF alpha. We have investigated the effects of recombinant human TNF alpha (rhTNF alpha) on osteoclast development and osteoclastic resorption in two different in vitro resorption systems which are each characterized by a different stage of development of the osteoclast. The effects were further compared to those of bovine PTH-(1-84). rhTNF alpha at concentrations between 0.01-50 ng/ml (3 x 10(-13) to 1.5 x 10(-9) M) did not alter the activity of mature osteoclasts, measured as 45Ca release in fetal mouse radii. In the osteoclast precursor dependent system (fetal mouse metacarpals) rhTNF alpha had a biphasic effect. It stimulated resorption dose-dependently from 0.01 ng/ml onward, with a maximal response at 0.5 ng/ml. At concentrations above 10 ng/ml rhTNF alpha, resorption was inhibited. In experiments in which irradiation was used to block replication, it was found that TNF alpha stimulates the proliferation of osteoclast progenitors at both low and high concentrations. As a result, at relatively low concentrations, more osteoclasts were formed in the calcified matrix, coinciding with an increased release of 45Ca. However, at relatively high concentrations, the increase in osteoclast progenitors did not lead to increased resorption, since the putative osteoclast progenitors were arrested in the periosteum. In comparison, bovine PTH-(1-84) stimulated resorption independent of proliferation by enhancing the differentiation of postmitotic osteoclast precursors and activating mature osteoclasts. In conclusion, the effects of TNF alpha on osteoclastic resorption are dependent on the stage of osteoclast development and the concentrations applied. PMID- 1874191 TI - In vitro stimulation of stage-specific deoxyribonucleic acid synthesis in rat seminiferous tubule segments by interleukin-1 alpha. AB - Levels of rat testicular interleukin-1-like factor (tIL-1) have been shown to correlate with DNA synthetic activity during the cycle of the rat seminiferous epithelium, suggesting its role as a spermatogonial or meiotic growth factor. To explore this further, a new in vitro model system was developed. Rat seminiferous tubule segments from stages I, V, VIIa, and VIII-IX of the cycle were isolated by transillumination-assisted microdissection, cultured in chemically defined serum free medium supplemented with human recombinant IL-1 alpha, and labeled with [3H]thymidine. During incubation, spontaneous progression of spermatogenesis was noted. Inactive stage VIIa tubule segments differentiated to stage VIII and initiated DNA synthesis, and concomitantly started to secrete IL-1-like factor. DNA synthesis of stages VIII-IX ceased through differentiation of spermatocytes to leptotene-zygotene (stages XII-XIII of the cycle). IL-1 alpha stimulated DNA synthesis significantly in spermatogonia of stage I. Meiotic DNA synthesis at stage VIIa was stimulated (48 h/34 C) and maintained at stages VIII-IX (48 h/34 C). IL-1 alpha seems to act as a regulator of spermatogenic DNA synthesis in both mitotic and meiotic phases. It has mainly stimulating and maintaining effects, but it may also be inhibitory under certain conditions. PMID- 1874192 TI - Tissue distribution, characterization, and regulation of messenger ribonucleic acid for growth hormone receptor and serum binding protein in the rat. AB - The distribution of GH receptor (GHR) and GH-binding protein (GHBP) mRNAs in multiple rat tissues was examined by Northern blotting using a cDNA fragment encoding the common extracellular domain of the GHR and the serum GHBP. Both GHR and GHBP mRNAs [4.5 and 1.2 kilobases (kb), respectively] were present in liver, kidney, adrenal, heart, muscle, ovary, mammary gland, gastrointestinal tract, and adipose tissue, but were barely or not detectable in testis, thymus, or brain. These observations suggest that GH exerts direct effects across a broad spectrum of rat tissues. Nuclease protection analysis also confirmed the presence in extrahepatic tissues of a GHR mRNA with up to 50% of the cytoplasmic domain being identical in sequence to that of the hepatic GHR mRNA. This suggests, but does not prove, that different receptor classes with differing intracellular signalling mechanisms may not exist. It is also clear from our studies that liver was the most abundant source of the truncated (1.2 kb) mRNA and is, therefore, believed to be the primary site of GHBP synthesis. Also, more importantly, at least in the rat, it was only GHBP mRNA that was up-regulated to any extent during pregnancy (female vs. pregnant, P less than 0.001). No significant changes were observed in the abundance of the full-length (4.5 kb) GHR mRNA. This pregnancy-related change in GHBP mRNA was also accompanied by a comparable increase in the actual level of measurable serum GHBP (female vs. pregnant, P = 0.005). Little change was seen in hepatic membrane binding. These data suggest that the GHBP and GHR are both widely coexpressed, but that the expression is not always coordinately regulated. This raises the possibility that the GHBP and GHR may have distinct roles in the regulation of GH delivery and action. PMID- 1874193 TI - Role of the thyroid gland in seasonal reproduction. III. Thyroidectomy blocks seasonal suppression of gonadotropin-releasing hormone secretion in sheep. AB - Previous studies demonstrated that the thyroid gland is required for the changes in LH secretion that lead to the end of the breeding season of female sheep, a reproductive transition generated within the ewe by an endogenous annual rhythm. The present study tested the hypothesis that this role of the thyroid is mediated via the GnRH neurosecretory system. The pulsatile secretion of GnRH into hypophyseal portal blood and LH into peripheral blood, as well as the neuroanatomical distribution of GnRH neurons and their light microscopic morphology, were compared among anestrous ewes and thyroidectomized (THX) ewes that failed to make the transition to the anestrous season. The study was conducted under photoperiodic conditions in which the transition to anestrus was generated by the endogenous rhythm. Each animal was ovariectomized and treated sc with a constant release implant of estradiol to normalize gonadal steroid status among thyroid-intact and THX ewes. High frequency pulses of GnRH and LH were evident in THX ewes that failed to make the transition to anestrus, whereas pulsatile secretion of GnRH and LH was generally not observed in thyroid-intact controls that had entered anestrus. This marked effect of thyroidectomy on GnRH secretion was not associated with widespread changes in the total number, distribution, or light microscopic morphology of GnRH neurons in the hypothalamus and preoptic area. Our finding that pulsatile secretion of GnRH is elevated in THX ewes that fail to make the transition to anestrus supports the hypothesis that the thyroid gland is required for the endogenously generated switch in function of the GnRH neurosecretory system that leads to the end of the breeding season of the ewe. PMID- 1874194 TI - Population density alters the responsiveness of GH4C1 pituitary tumor cells to 17 beta-estradiol. AB - In this study we have examined the effect of population density on the ability of 17 beta-estradiol (E2) to induce PRL mRNA, DNA synthesis, and progesterone receptor in GH4C1 pituitary tumor cells. These parameters were examined at three subconfluent population densities that varied over a 4-fold range. The culture medium was changed daily in these experiments to reduce the possibility of nutrient depletion, medium toxification, or E2 metabolism. At the low population density, a 5-day treatment with E2 at a concentration of 1.0 nM resulted in an 8.1-fold increase in the level of PRL mRNA, as measured by the cytosolic dot blot procedure. At the intermediate density, E2 induced PRL mRNA 2.4-fold. At the high density, the level of PRL mRNA was reduced by 50% in response to 5 days of treatment with E2. The cytosolic dot blot procedure would reflect changes in the level of PRL mRNA per cell as well as changes in the number of cells per culture. Therefore, the level of beta-actin mRNA was also measured, assuming that it would remain constant on a per cell basis. When the level of PRL mRNA was normalized to the level of beta-actin mRNA in the same cytosols, E2 increased PRL mRNA 2.6-fold in the low density cultures and 1.9-fold in the intermediate density cultures, and had no effect on the level of PRL mRNA in the high density cultures. The effect of population density on the induction of GH4C1 cell proliferation by E2 was examined directly by measuring cellular DNA, thymidine incorporation by whole cells, and deoxythymidine triphosphate (dTTP) incorporation by isolated nuclei. At the low density, E2 initially stimulated GH4C1 cell proliferation, as evidenced by an increased rate of dTTP incorporation. However, this stimulatory effect was lost by day 5 of treatment, as the population density of the E2 treated low density cultures increased. At the high density, the inhibitory effect of E2 on dTTP incorporation was observed by day 2 of treatment and thereafter become more pronounced. These stimulatory and inhibitory effects of E2 were also revealed when the level of cellular DNA was measured. In contrast to the effects of population density on the induction of PRL mRNA and cell proliferation, an increase in density had no observable effect on the induction of progesterone receptor by E2. These data illustrate the critical importance of the culture environment in studies examining estrogen action in vitro. PMID- 1874195 TI - Antibodies to cytoplasmic sequences of cloned liver growth hormone (GH) receptors recognize GH receptors associated with tyrosine kinase activity. AB - GH stimulates tyrosyl phosphorylation of GH receptors in 3T3-F442A fibroblasts, and highly purified GH receptor preparations exhibit tyrosine kinase activity. Paradoxically, however, the GH receptor cloned from liver exhibits no sequence similarity to receptors with known signal transduction mechanisms, including those exhibiting ligand-activated tyrosine kinase activity. These observations raise the possibility that there are two kinds of receptors for GH: the first represented by the cloned liver GH receptor, and the second by a tyrosine kinase containing GH receptor. To inquire into the possibility of two distinct GH receptors, we determined whether the cloned liver GH receptor shares structural similarities with the tyrosine kinase-associated GH receptor. When the cloned rabbit liver GH receptor is expressed in human kidney 293 cells, it migrates with a mol wt appropriate for the tyrosine kinase-associated GH receptor, despite the calculated mol wt of the cloned GH receptor being 60,000 smaller than that of the tyrosine kinase-associated GH receptor. The recognition of tyrosine kinase associated GH receptor by antipeptide antibodies to three different epitopes on the cytoplasmic domain of the cloned liver GH receptor was also tested. Tyrosyl phosphorylated [125I]human GH-receptor complexes were prepared by immunoprecipitation with phosphotyrosyl-binding antibody; this subpopulation of GH-receptor complexes was recognized by all three antipeptide antibodies. The antibodies also recognized similarly isolated tyrosyl phosphorylated GH-receptor complexes, which had been further phosphorylated in solution on tyrosyl residues upon addition of [gamma 32P] ATP. Furthermore, highly purified GH receptors prepared by sequential immunoprecipitation using phosphotyrosyl-binding antibody and any one of the three antipeptide antibodies incorporated 32P into tyrosyl residues upon the addition of [gamma 32P] ATP. These results provide evidence that tyrosine kinase-associated GH receptors share sequence similarity in the cytoplasmic domain with the cloned liver GH receptor. The cloned GH receptor and the tyrosine kinase-associated GH receptor, therefore, are likely to be the same receptor or related receptor isoforms. PMID- 1874196 TI - Expression of the androgen receptor gene in rat penile tissue and cells during sexual maturation. AB - The cessation of rat and human penile growth at completion of sexual maturation appears to be related to a tissue-specific decrease in the number of androgen receptors (AR) in the penis. To find out whether this is due to either transcriptional or translational regulation of the AR gene, we determined the levels of AR mRNA by Northern blots in the corpora cavernosa from groups of 16-, 19-, 22-, 27-, 52-, and 90-day-old rats. The AR mRNA rapidly decreases with age and is nearly undetectable in the 52- and 90-day-old rats, paralleling the decline in AR number. The persistence of a low amount of AR mRNA in the adult penis was confirmed by reverse transcription/polymerase chain reaction amplification of total RNA, and its level was estimated by a semiquantitative modification of this procedure at less than 1/25th of that found in the youngest rats. Smooth muscle cells derived from the 16- and 90-day-old corpora cavernosa express in the AR gene in vitro in approximately the same levels, suggesting that there are factors in culture that up-regulate the AR mRNA. Our results are compatible with the assumption that the age-dependent decrease in AR in the rat penis is due to transcriptional regulation, although they do not exclude the less likely alternative of a selective effect on AR mRNA stability and support the use of this model for studying tissue-specific factors controlling the developmental expression of the AR gene. PMID- 1874197 TI - Rapid increase in LHRH mRNA levels following NMDA. AB - To test the hypothesis that changes in LHRH mRNA levels are tightly linked to changes in LHRH secretion, intact male rats were infused with NMDA, a substance which increases LH release by a hypothalamic action. NMDA significantly elevated cellular levels of LHRH mRNA at 15 and 60 min. Similar changes in LH levels were induced by NMDA. These effects of NMDA on LHRH mRNA levels were not due to a generalized excitatory effect in the brain because levels of mRNAs encoding proopiomelanocortin (POMC) and tyrosine hydroxylase (TH) in the arcuate periarcuate region were not altered by NMDA and levels of TH mRNA were decreased significantly at 15 and 60 min in neurons of the zona incerta. These data strongly support the hypothesis that changes in cellular levels of LHRH mRNA are tightly linked temporally to changes in LHRH secretion. PMID- 1874198 TI - Effects of deliberate hypotension induced by labetalol on renal function. AB - The effect of deliberate hypotension induced by labetalol on renal function, was studied in 25 patients undergoing middle-ear surgery. The patients were randomized into three groups, one enflurane (E) group and two isoflurane (I and F) groups. Group F received frusemide 0.5 mg kg-1 at the onset of hypotension. The mean arterial pressure was 50 mmHg (6.7 kPa) in Groups E and I, and 49 mmHg (6.5 kPa) in Group F during hypotension. During hypotension, urine flow rate, effective renal blood flow, endogenous creatinine clearance, and osmolar clearance decreased. Free-water clearance and fractional electrolyte excretions also indicated deterioration of renal function during hypotension, but it returned to normal after anaesthesia. The effects of frusemide appeared mainly after anaesthesia. Frusemide reduced the amount of labetalol and isoflurane needed to maintain hypotension. Serum fluoride concentration did not increase to a potentially nephrotoxic level. PMID- 1874199 TI - Sedation for paediatric computerized tomography--a double-blind assessment of rectal midazolam. AB - This double-blind study investigated the rectal administration of midazolam as an alternative to general anaesthesia for elective computerized tomography (CT) of the brain. Thirty children were randomly allocated to receive either midazolam 0.3 mg kg-1 (Group 1) or midazolam 0.6 mg kg-1 (Group 2) by the rectal route. Sedation was obtained in 13 children in Group 1 and 12 in Group 2 but this was only satisfactory for scanning in seven children in Group 1 and eight in Group 2. We concluded that although the technique produced sedation, it did not reliably produce satisfactory conditions for CT scanning. PMID- 1874200 TI - Comparison of inhalation induction with isoflurane or halothane in children. AB - Thirty-six children (mean age 2.4 years) premedicated with oral chloral hydrate 70 mg kg-1 and atropine 0.03 mg kg-1 were anaesthetized with either 3.75% isoflurane or 2.5% halothane in 70% nitrous oxide in oxygen. The eyelash reflex disappeared in 39 +/- 7 s (mean +/- SD) with isoflurane and in 56 +/- 16 s with halothane (P less than 0.001). Tachypnoea was seen with both anaesthetics. Coughing, breath holding, stridorous breathing and respiratory depression were seen during isoflurane but not during halothane induction (P less than 0.01). In nine of 20 children anaesthetized with isoflurane, the ventilation had to be assisted before intubation. Endotracheal intubation was possible in 224 +/- 35 s with isoflurane and in 281 +/- 64 s with halothane (P less than 0.01). Intubating conditions were satisfactory in 80% of the children anaesthetized with either volatile agent. Cardiovascular responses to endotracheal intubation were minimal with both anaesthetics. No cardiac dysrhythmias were noted. Heart rate was higher during isoflurane than during halothane induction. Diastolic arterial pressure was lower during isoflurane than during halothane induction immediately and 5 min after intubation. PMID- 1874201 TI - Lack of influence of acupuncture and transcutaneous stimulation on the immunoglobulin levels and leucocyte counts following upper-abdominal surgery. AB - The changes in immunoglobulins (IgA, IgG and IgM) and total and differential leucocyte counts in the peripheral blood during, and for 6 days after, surgery were evaluated in 29 male patients submitted to standardized upper-abdominal surgery performed under two different anaesthetic techniques. Group 1 received stimulation of ear and paravertebral points, supplemented by small doses of fentanyl (mean 1.2 micrograms kg-1, range 0.0-5.7) and Group 2 received moderate dose fentanyl (mean 22.9 micrograms kg-1, range: 17.5-29.8). All were induced with thiopentone 5 mg kg-1, intubated after vecuronium 0.1 mg kg-1 and ventilated with 67% nitrous oxide in oxygen. Inhalation anaesthesia was not used. Surgery was followed by a fall in immunoglobulins, lymphocyte and eosinophil counts and a rise in leucocyte and neutrophil counts in both groups (P less than 0.01). No recovery was observed until the last assessment on Day 6 after surgery in IgA, IgG, leucocyte, neutrophil and lymphocyte counts in both groups, whereas IgM and eosinophil counts recovered by Day 4. Monocyte and basophil counts were unchanged in either group. Acupuncture and transcutaneous stimulation analgesia performed for major abdominal surgery did not influence the body's immune system either during or after surgery as measured by the concentrations of immunoglobulin and total and differential WBC counts. PMID- 1874202 TI - Total intravenous anaesthesia in stereotactic surgery--one year's clinical experience. AB - The technique of stereotactic intracranial surgery is described together with a total intravenous anaesthetic technique (TIVA) using a propofol infusion, fentanyl, vecuronium and oxygen in air. One year's results are reported for patients undergoing biopsy or destruction of an intracranial lesion. This technique offered cardiovascular stability and an adequate depth of anaesthesia for the various stages required in stereotaxis. Recovery was rapid and with few side-effects. Duration of anaesthesia and total dose of propofol did not significantly prolong the time to recovery. PMID- 1874203 TI - Hemocue--a new haemoglobinometer in the clinic. AB - The accuracy of the Hemocue, a portable haemoglobinometer, was tested on 29 patients undergoing open-heart surgery, and the results were compared with the haemoglobin values obtained from the hospital laboratory. Special attention was paid to the lower range of haemoglobin values and the simplicity and speed of operating the meter. The correlation between the methods was good (r = 0.965). The limits of agreement were 0.0323 +/- 0.705 mmol l-1 (95% confidence level). PMID- 1874204 TI - Post-operative headache--a multifactorial analysis. AB - ASA Grade I and II patients admitted for day-case urological surgery received no premedication or an oral dose of temazepam 10 mg. Anaesthesia was induced with methohexitone and maintained with nitrous oxide, oxygen and halothane or enflurane via a Mapleson A circuit. The incidence of post-operative headache was investigated by an independent observer. Eighty patients were studied (50 male and 30 female) of whom 32 (40%) had post-operative headaches. Post-operative headache was significantly correlated with female sex and frequent 'normal' headache occurrence. The lack of previous surgical experience was a significant risk factor and a loose insignificant association existed with age, the use of halothane and the presence of pre-operative headache. Temazepam premedication had no effect and was associated with significantly more patients complaining of feeling cold. PMID- 1874205 TI - Communication during the pre-operative visit. AB - Eighty-six patients completed a questionnaire about what they expected from a pre operative visit by an anaesthesiologist. Ninety-one per cent of the patients wanted a detailed and informative conversation. The patient's previous knowledge stemmed primarily from lay sources, such as other patients and visitors. Age and marital status influenced the extent of the patient's previous knowledge. PMID- 1874206 TI - Coronary-artery spasm during spinal anaesthesia in a patient with primary hyperparathyroidism. PMID- 1874207 TI - Haemodynamic and endocrine effects of deliberate hypotension with magnesium sulphate for cerebral-aneurysm surgery. AB - Deliberate hypotension is widely used during cerebral-artery aneurysm surgery to facilitate clipping and to prevent rupture. A large number of drugs are commonly employed to achieve hypotension, but all have their specific drawbacks. We investigated the effects of magnesium-sulphate-induced hypotension on haemodynamics, as well as on plasma catecholamine and renin concentrations in 11 patients undergoing cerebral-aneurysm surgery. Magnesium sulphate lowered blood pressure by reducing systemic vascular resistance. There was no reflex tachycardia or rebound hypertension, and cardiac output was not decreased. Plasma renin activity increased during hypotension but the inhibitory effects of magnesium on angiotensin converting enzyme prevented angiotensin-II-associated hypertension. Plasma catecholamine concentrations increased moderately during hypotension. Renal perfusion was not impaired since diuresis remained constant or even improved during and after hypotension. Magnesium sulphate in high doses has major drawbacks, however, among which are enhanced neuromuscular blockade and delayed return of consciousness. Although the haemodynamic effects of magnesium sulphate during hypotension appear to be beneficial, these side-effects might limits its usefulness, particularly in neurosurgery. More research must be conducted before magnesium sulphate can be considered a routine method. PMID- 1874208 TI - Effects and arterial concentration of prostaglandin E1 during cardiopulmonary bypass. AB - The effects an infusion prostaglandin E1 (PGE1) on both haemodynamics and PGE1 arterial blood concentration during and after cardiopulmonary bypass (CPB) were studied in 15 patients (eight patients received PGE1 30 ng kg-1 min-1; seven served as controls and did not receive PGE1 administration). Mean arterial blood pressure and systemic vascular resistance were significantly lower in the PGE1 group than in the control group during CPB. There were no statistically significant differences between the two groups with regard to mean pulmonary artery pressure, central venous pressure, and cardiac or perfusion index. The arterial blood concentration of PGE1 in the control group during CPB was about 50 pg ml-1. In the PGE1 group it increased rapidly after the beginning of CPB and reached a level of 1500 pg ml-1 at 60 min of CPB. After weaning off CPB, PGE1 concentration decreased rapidly to 70 pg ml-1 in spite of the continuous PGE1 infusion. It is concluded that the metabolism of PGE1 is strongly inhibited during CPB and the effects of PGE1 may be unexpectedly heightened. Therefore, the infusion rate of PGE1 during CPB should be 30 ng kg-1 min-1 or less in order to avoid severe hypotension. PMID- 1874209 TI - Pharmacokinetics and clinical response of hyoscine plus morphine premedication in connection with cardiopulmonary bypass surgery. AB - Plasma hyoscine and morphine levels and various pharmacodynamic responses have been examined in seven patients scheduled for a coronary-artery bypass graft. Hyoscine 0.006 mg kg-1 and morphine 0.20 mg kg-1 were administered intramuscularly as routine premedication. Surgery was performed using high-dose fentanyl anaesthesia (100 micrograms kg-1). The clinical responses followed were heart rate, blood pressure, subjective sedation and antisialogogue effect. The plasma hyoscine levels were determined by radioreceptor assay, and plasma morphine levels by liquid chromatography, both up to 24 h. The maximum levels of plasma hyoscine (6.6 micrograms l-1) and morphine (158 micrograms l-1) and the time they were reached (13.0 and 9.7 min, respectively) were comparable with the values obtained in earlier studies using young healthy subjects. After the start of cardiopulmonary bypass, significant decreases in plasma levels of both hyoscine and morphine were found. The elimination half-life of hyoscine in the plasma was 2.4 h, which is somewhat greater than obtained in earlier studies with young healthy patients under regional anaesthesia. Elimination of plasma morphine (t1/2el = 3.3 h) was not significantly altered by the procedure. The sedative and antisialogogue effects of the drugs appeared quickly and were significant, but no tachycardia or other side effects were observed. In conclusion, the kinetic properties of both hyoscine and morphine are suitable for routine use as premedicants before cardiac surgery. PMID- 1874210 TI - Etomidate vs. propofol to carry out suspension laryngoscopies. AB - Patients about to undergo a suspension laryngoscopy were randomly assigned to one of two groups (n = 10). They were given either etomidate 1 mg kg-1 followed by 1 mg kg-1 h-1, or propofol 2.5 mg kg-1 followed by 9 mg kg-1 h-1. Alfentanil 10 micrograms kg-1 was given to provide analgesia with a further half dose if necessary. Duration of apnoea, quality of anaesthesia, times between stopping hypnotic administration and the moment when the patients opened their eyes, gave their name, date of birth and the day's date were noted. Heart rate, blood pressures, respiratory frequency and blood gases were noted before induction, before suspension and when hypnotic infusion was stopped. Clinical tolerance was good, the duration of surgery, apnoea and quality of anaesthesia were the same for both groups. Blood pressure was less depressed by etomidate, but ventilatory frequency was higher. Recovery was significantly faster after propofol. Propofol is recommended for patients who require good post-operative cooperation (chronic obstructive pulmonary disease) and etomidate for those who are haemodynamically compromised. PMID- 1874211 TI - Intrapleural bupivacaine analgesia after thoraco-abdominal incision for oesophagectomy. AB - Intrapleural bupivacaine administration is said to produce good analgesia for the pain induced by a subcostal incision. However, reports of its efficacy after thoracotomy are conflicting. The goal of this study was to compare the analgesia produced by intrapleural administration of bupivacaine after oesophagectomy using a thoraco-abdominal incision with that obtained from intrapleural saline. After informed consent and institutional approval were obtained, 20 patients were randomly assigned to two groups of 10 patients each. Subjects received intrapleurally 10 ml of either 0.25% bupivacaine with 1:200,000 adrenaline or normal saline, every 8 h, beginning on the first post-operative day and lasting for 4 days. Pain was evaluated using a visual-analogue scale 2 h after the first daily treatment at rest and during physiotherapy. Pain scores were significantly lower in the bupivacaine group than in the saline group. Additionally, PaO2 was significantly higher in the bupivacaine group than in the saline group on Day 1 (P less than 0.05). The plasma bupivacaine concentration never reached the level of toxicity. Plasma bupivacaine concentrations on Day 1 after the first intrapleural bupivacaine injection were less than 350 ng ml-1; on Day 4 after the last injection they were less than 1300 ng ml-1. In conclusion, intrapleural administration of bupivacaine produces effective analgesia after oesophagectomy performed with a thoracoabdominal incision. The technique is easy to perform and is safe. PMID- 1874212 TI - Propofol and alfentanil infusions for sedation in intensive therapy. AB - Forty-four patients, with admission APACHE II scores between 5 and 24, undergoing mechanical ventilation in the intensive therapy unit, received a sedative regimen consisting of continuous infusions of propofol and alfentanil. Patients were randomly allocated to one of three groups to receive either alfentanil 0.25 microgram kg-1 min-1 (10 patients), 0.50 microgram kg-1 min-1 (15 patients) or 0.75 microgram kg-1 min-1 (18 patients) for analgesia. An infusion of propofol 20 200 mg h-1 ran concurrently to maintain a satisfactory level of sedation. Patients received the infusions for between 4 and 260 h and 38 patients spent more than 90% of this time at satisfactory sedation levels. After stopping the infusions all patients had short times to wakening (mean 3-18 min) and to establish spontaneous respiration (mean 8-28 min), suggesting no significant cumulation. Some depression of blood pressure was seen on starting the infusions, which was in general easily treated with fluids or small increases in inotropic agents. One patient, however, was withdrawn from the trial because of haemodynamic instability. This combination of drugs can be recommended for sedation of general intensive-therapy patients, provided the cost is not felt to be prohibitive. PMID- 1874213 TI - Phenylephrine in a hypoxaemic spell. PMID- 1874214 TI - Tension pneumothorax possibly due to the placement of a Swan-Ganz catheter detected by changes in the ventilator. PMID- 1874215 TI - Evoked potentials in anaesthesia. PMID- 1874216 TI - Coronary circulation and factors affecting coronary 'steal'. PMID- 1874217 TI - Cerebral blood flow and metabolism during hypotension induced with sodium nitroprusside and metoprolol. AB - Cerebral blood flow (CBF) and metabolism have been studied during general anaesthesia with enflurane and hypotension induced with sodium nitroprusside (SNP) in combination with metoprolol in nine ASA Grade I patients undergoing surgery for deviation of the nasal septum. Mean arterial pressure (MAP) was reduced by 31% to a mean of 47 mmHg using metoprolol 0.15 mg kg-1 and SNP 0.46 mg kg-1. There was no reduction in CBF during the hypotensive period. Cerebral metabolic rate of oxygen (CMRO2) was also unchanged during hypotension. We conclude that in healthy individuals anaesthetized with enflurane, SNP in combination with metoprolol reduces MAP to the desired level without changing CBF or CMRO2. PMID- 1874218 TI - Verapamil and nitrous oxide exert only minor effects on the normal myocardium in the presence of fentanyl. AB - While the association of inhalational anaesthetics and verapamil has been shown to cause myocardial dysfunction, the interactions between fentanyl, verapamil and nitrous oxide on regional function in normal hearts have not been investigated. Seven mongrel dogs were instrumented to measure aortic and left-ventricular pressure, aortic blood flow and apical and basal regional left-ventricular function (sonomicrometry). Haemodynamic values were recorded during anaesthesia with 1% halothane, fentanyl 100 micrograms kg-1 (followed by 1.5 micrograms kg-1 min-1) and then after the addition of verapamil 250 micrograms kg-1 over 30 min (followed by 60 micrograms kg-1 min-1). At each stage 67% nitrous oxide was added and recordings obtained before and during its administration. The addition of verapamil during fentanyl anaesthesia caused a moderate depression of global haemodynamics. Only little dysfunction of the apical region (9.5 +/- 2.4% post systolic shortening) was noted. The addition of nitrous oxide caused a small amount of additional depression without significant regional dysfunction. PMID- 1874219 TI - Awakening and recovery of simple cognitive and psychomotor functions 2 h after anaesthesia for day-case surgery--total intravenous anaesthesia with propofol alfentanil versus thiopentone-alfentanil. AB - Fifty-seven patients undergoing minor out-patient gynaecological procedures were allocated to one of two total intravenous anaesthesia regimes: propofol and alfentanil or thiopentone and alfentanil. Diazepam was given orally as premedication. To assess objectively the quality of recovery, the patients underwent a number of tests pre-operatively and two hours post-operatively. The time to opening of eyes and orientation was equal in both groups, as was the recovery of the tested cognitive and psychomotor functions after 2 h, when the score in both groups had returned to baseline. We conclude that the use of propofol instead of thiopentone for shorter surgical procedures gives no advantage as regards length of stay in hospital. PMID- 1874220 TI - The influence of etomidate upon cerebral metabolites after complete brain ischaemia in the rat. AB - The influence of etomidate on post-ischaemic cerebral metabolism was examined in 1-year-old male Wistar rats. Ten rats were randomly allocated to each of three groups. Group 1 animals received etomidate for 60 min without undergoing cerebral ischaemia. In Group 2, there was a 60-min recovery period following 15 min of complete cerebral ischaemia. Etomidate was administered to Group 3 animals after 15 min of ischaemia. At the end of the study period, the brains were frozen in situ using liquid nitrogen. The cortex was then biochemically analysed. Considering glycolysis as well as the citric-acid cycle, the pattern of metabolite changes with etomidate application was almost identical to the pattern of spontaneous recovery. The content of energy-rich phosphates was reduced when Groups 2 and 3 were compared with the non-ischaemia group, indicating previous depletion of energy reserves of brain tissue. However, the energy charge as a parameter of energy balance had already been returned to normal values. We conclude that post-ischaemic application of etomidate has no favourable effect on recovery after complete cerebral ischaemia in the rat. PMID- 1874221 TI - Immunomodulating effects of halothane in mice. AB - Twenty mice were acutely exposed to 1.5% halothane anaesthesia for 4 h. The mice were sequentially killed during the first 3 days after halothane exposure. Another 14 mice were chronically exposed to 0.25% halothane for 1 h daily, four times weekly for 3 months. The mice were sequentially killed every week. Acute exposure to halothane anaesthesia resulted in an increase in lymphocyte count per spleen, a decrease in serum IgG concentrations (Day 2), a reduction in spontaneous 3H-thymidine lymphocytic uptake (Day 1), and an increase in concanavalin-A-stimulated uptake. All immunometric assays returned to control levels on Day 3 after halothane exposure. Chronic non-anaesthetic concentrations of halothane exposure produced a decrease in serum IgG concentrations and an increase in spontaneous and stimulated lymphocyte 3H-thymidine uptake. It is concluded that acute exposure of mice to anaesthetic halothane results in a transient depression of the immune response, while chronic non-anaesthetic concentrations produce a differential effect on the two moieties of the immune system, a depressed humoral response and overactive cellular response. PMID- 1874222 TI - Intracranial subdural haematoma--a rare complication after spinal anaesthesia. PMID- 1874223 TI - Somatosensory evoked responses during and after graded brain ischaemia in goats. AB - Somatosensory evoked potentials (SEPs) were studied during graded incomplete cerebral ischaemia in eight goats and for the following 2 h. Anaesthesia was maintained with etomidate 1-1.5 mg kg-1 h-1 and 50% nitrous oxide in oxygen. Global cerebral blood flow (gCBF) was measured by a magnetic flow transducer at one internal maxillary artery after surgical occlusion of all other major extracranial cerebral arteries. CBF was reduced every 30 min by 25% with a lower limit of 15-20 ml 100 g-1 min-1. Regional cerebral blood flow (rCBF) in the brainstem and cortex was measured by the microsphere technique. The main findings were: (a) a graded decline in cortical SEP and a concurrent prolongation of the central conduction time (CCT) at gCBF values below 35 ml 100 g-1 min-1 and (b) an incomplete recovery of cortical SEP components during recirculation. Reduction of gCBF affected cortical rCBF more severely than brainstem rCBF. As a result, only cortical SEPs were changed. Our data suggest that reduced cerebral perfusion may result in altered cortical brain electrical activity that may be monitored by SEP recordings. PMID- 1874224 TI - Effect of sub-anaesthetic infusions of propofol on peak velocity of saccadic eye movements. AB - Peak velocity of saccadic eye movements was studied in six healthy volunteers who received either 0.9% sodium chloride (as a control) or a stepwise rising propofol infusion regime of 0.24, 0.6 and 1.5 mg kg-1 h-1, which produced arterialized venous concentrations equivalent to 1%, 6% and 13% of the estimated EC50 for propofol. The infusion lasted for 75 min (25 min at each infusion rate) and was followed by a 2-h post-infusion recovery period. Peak saccadic velocity was highly significantly depressed during the 15-25-min period after the start of the second and third propofol infusions compared with saline. The relationship between arterialized venous blood concentration and peak saccadic velocity was similar during recovery when concentrations were falling to that during increasing blood propofol concentrations. Peak saccadic velocity decreased linearly with increasing log10 propofol concentration in the range of 25-800 ng ml-1 (14% of control per decade). Measured arterialized venous-blood propofol concentrations were variable, and systematically greater than computer predictions at the two higher infusion rates. In only half the subjects were the subjective assessments significantly correlated with log10 propofol concentrations or with percentage reduction in peak saccadic velocity. PMID- 1874225 TI - Fibre-optic bronchoscopic evaluation of tracheal tube position. AB - Verification of tracheal tube position by fibre-optic bronchoscopy was evaluated in 20 critically ill adult patients. The distance between the carina and the tube was measured by direct visualization with a fibre-optic bronchoscope and compared with the corresponding measurement obtained from a concomitant chest radiograph. The measured values did not differ significantly and in 18 out of 20 patients the accuracy was within 2 cm. No adverse effects were observed. We conclude that verification of tracheal tube position by fibre-optic bronchoscopy is a safe alternative to chest X-ray. PMID- 1874226 TI - Post-operative analgesia following femoral-neck surgery--a comparison between 3 in 1 femoral nerve block and lateral cutaneous nerve block. AB - A prospective controlled randomized trial on patients receiving surgery for fractured neck of femur was carried out, in which post-operative analgesic requirements in three separate groups were compared. Patients in Group 1 acted as controls, whilst those in Groups 2 and 3 received lateral cutaneous nerve blocks and 3 in 1 femoral nerve blocks, respectively. Patients in Group 3 needed significantly less analgesia than the other two groups, and the time to first administration of analgesia was significantly longer. No complications of either of the nerve blocks was noted. PMID- 1874227 TI - The cuffed pharyngeal airway. AB - A new self-retaining nasopharyngeal airway is described. The clinical performance of this airway was assessed in 100 patients during anaesthesia with spontaneous respiration. The physical behaviour of the airway was investigated in four patients. In an additional 25 patients the tube was used via the oral route. Although designed for use by the nasal route, the airway can be used as a self retaining oropharyngeal airway. PMID- 1874228 TI - Transfusion in the exsanguinating Jehovah's Witness patient--the attitude of intensive-care doctors. AB - The attitude of a Jehovah's Witness patient refusing a blood transfusion during an exsanguinating episode can raise important ethical problems. Various ethical principles, including the patient's autonomy, the sanctity of life and the dignity of the medical profession can be confronted. A total of 242 doctors, members of the European Society of Intensive Care Medicine, answered a questionnaire indicating that 63% would transfuse in those circumstances. However, 26% would never inform the patient about this. Only 45% considered the blood transfusion as appropriate, of whom 25% were unable to define the best option. Doctors from France and Italy more commonly transfuse while those from The Netherlands, the United Kingdom and Scandinavia more commonly withhold transfusion. These data stress the need for a definition of the appropriate medical attitudes towards the patient refusing blood transfusion. PMID- 1874229 TI - Anaesthetic management of dilated cardiomyopathy with severe ventricular dysrhythmias. AB - A 67-year-old man with dilated cardiomyopathy underwent subtotal gastrectomy. The risks due to anaesthesia and surgery were considered to be very high because of the severe dysrhythmias and renal dysfunction. Anaesthesia was induced with fentanyl and midazolam and maintained with additional fentanyl, midazolam, and 60% nitrous oxide. Dobutamine, dopamine, lignocaine and a temporary pacemaker were used to control cardiovascular responses during surgery. Mild hypotension and tachycardia occurred, but neither circulatory failure nor other major complications were observed during and after the operation. PMID- 1874230 TI - Dystrophia myotonica--emergency caesarean section with spinal anaesthesia. PMID- 1874231 TI - Safety testing the Bain circuit--a new test adaptor. PMID- 1874232 TI - European Academy of Anaesthesiology 2nd open annual meeting. Mainz, 1-3 March 1990. Abstracts. PMID- 1874233 TI - Evidence of fibre hyperplasia in human skeletal muscles from healthy young men? A left-right comparison of the fibre number in whole anterior tibialis muscles. AB - Cross-sections (thickness 10 microns) of whole autopsied left and right anterior tibialis muscles of seven young previously healthy right-handed men (mean age 23 years, range 18-32 years) were prepared for light-microscope enzyme histochemistry. Muscle cross-sectional area and total number of fibres, mean fibre size (indirectly determined) and proportion of the different fibre types (type 1 and type 2 on basis of myofibrillar adenosine triphosphatase characteristics), in each muscle cross-section were determined. The analysis showed that the cross-sectional area of the left muscle was significantly larger (P less than 0.05), and the total number of fibres was significantly higher (P less than 0.05), than for the corresponding right muscle. There was no significant difference for the mean fibre size or the proportion of the two fibre types. The results imply that long-term asymmetrical low-level daily demands on muscles of the left and the right lower leg in right-handed individuals provide enough stimuli to induce an enlargement of the muscles on the left side, and that this enlargement is due to an increase in the number of muscle fibres (fibre hyperplasia). Calculations based on the data also explain why the underlying process of hyperplasia is difficult, or even impossible, to detect in standard muscle biopsies. PMID- 1874234 TI - Cardiopulmonary responses to combined rhythmic and isometric exercise in humans. AB - A rhythmic (R) and an isometric (I) exercise were performed separately and in combination to assess their additive effects on arterial systolic (P(as)) and diastolic (P(ad)) blood pressures, heart rate (fc), and minute ventilation (VI). The isometric effort consisted of a 40% maximal voluntary handgrip contraction (MVC) performed for a duration of 80% of a previously determined 40% MVC fatiguing effort. The R effort consisted of a 13-min cycle effort at 75% maximum oxygen consumption (VO2max). For the combined efforts, I was performed starting simultaneously with or ending simultaneously with R. Data on nine subjects yield statistically significant evidence (P less than 0.05) that the effects of I and R are not additive for the following three cases: (1) P(as) when I and R are ended simultaneously (I alone = 4.9, SEM 0.5 kPa increase; R alone = no significant change from steady state; I + R = 1.2, SEM 0.4 kPa increase), (2) P(ad) when I and R are started simultaneously (I alone = 4.1, SEM 0.4 kPa increase; R alone = 0.7, SEM 0.3 kPa decrease; I + R = 1.9, SEM 0.4 kPa increase), and (3) P(ad) when I and R are ended simultaneously (I alone = 4.1, SEM 0.4 kPa increase; R alone = 0.3, SEM 0.5 kPa decrease; I + R = 0.8, SEM 0.3 kPa increase). For all other variables and cases, there is not sufficient evidence to conclude that the effects of I and R are not additive. We conclude that R and I exercises do not invariably produce strictly additive cardiopulmonary responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874235 TI - Electromyographic changes in the isolated rat diaphragm during the development of fatigue. AB - To investigate whether the power spectrum of the electromyogram of a fatiguing muscle can be used to infer the degree to which the muscle is fatigued, we recorded isometric tension and two monopolar electromyograms from eight isolated rat diaphragm preparations suspended in an organ bath containing a balanced salt solution. Each preparation was excited with a fixed phrenic nerve impulse pattern made up of a 70-Hz train of impulses of supramaximal voltage delivered for 170 ms with a 500-ms recovery period. Tension fell rapidly over the first 60 s of the fatigue run and more slowly for the remaining 60 s analysed. The duration of extracellular action potentials increased and their amplitude decreased as the tension developed by the diaphragm decreased; conduction velocity along muscle fibres also decreased. The centroid frequency (fcen) of the power spectrum of the first action potential elicited by each train of stimuli decreased rapidly until tension fell to approximately 70% of the initial value; thereafter little change in fcen occurred, although tension continued to fall to 33% of its initial value. Our results demonstrated that under controlled conditions, fcen provided a sensitive index of fatigue in its early stages, but provided no information once fatigue was pronounced. PMID- 1874236 TI - Effect of an iron supplement on body iron status and aerobic capacity of young training women. AB - Serum iron deficiency has a high incidence in female athletes. We investigated the effects of a daily oral iron supplement, (160 mg) administered during an intensive 7-week physical training programme, on body iron status, and the maximal aerobic capacity (VO2max) of 13 women (group A) compared to 15 who took a placebo (group B). The subjects were 19 years old. Blood samples were obtained before training began and on days 1, 7, 21 and 42 of training. They were analysed for packed cell volume (PVC) and for haemoglobin (Hb), 2,3-diphosphoglycerate (2,3-DPG), haptoglobin, iron and ferritin concentrations. The VO2max was measured on days 0, 21 and 42 of training. Following 21 days of training Hb, PCV and ferritin were significantly higher (P less than or equal to 0.01) in group A compared to group B. Over the training period Hb rose by 9.3% and 2.4% in groups A and B, respectively. At the end of training 66% of group B exhibited ferritin concentrations below 10 ng.ml-1, while none of group A had such low values. Mean VO2max of group A had increased by 7.5% following 21 days of training (P less than or equal to 0.01) and by 15.3% after 42 days. No appreciable increase in VO2max had occurred in group B by day 21 (significantly lower than VO2max of group A; P less than or equal to 0.05), however by day 42 it had increased by 14.3% (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874237 TI - Experimental studies on the effects of vibration and noise on sympathetic nerve activity in skin. AB - Multi-unit sympathetic activity was recorded at elbow level from median nerve fascicles supplying glabrous skin of the left hand in five healthy subjects. The resultant vasomotor responses accompanying the neural activity were monitored by simultaneous recordings of skin blood flow using the laser doppler method and skin temperature in the innervation zones. No significant change in sympathetic activity was observed during handgrip exercise of the right hand under a constant gripping force of 2 kg. Subjects maintained the same gripping force of the right hand during exposure in random order to local vibration and/or noise, each type of exposure lasting 5 min with intervals of 20 min. A two-peaked significant increase in outflow from sympathetic nerves was observed during local exposure of the right hand to vibration with a frequency of 60 Hz and an acceleration of 50 m.s-2, followed by a postexposure period which revealed a relative suppression of sympathetic nerve activity and a significant increase in blood flow. Noise at 100 dB(A) showed only an initial effect on skin sympathetic nerve activity (SSA), whereas when combined with local vibration at 60 Hz, a pronounced increase in neural activity was noticed, indicating a combined effect of vibration and noise. These results from direct recordings of SSA suggest a sympathetic vasomotor reflex mechanism triggered by local vibration stimuli to the hand. PMID- 1874238 TI - The interstitial fluid content in working muscle modifies the cardiovascular response to exercise. AB - The volume of interstitial fluid in the limbs varies considerably, due to hydrostatic effects. As signals from working muscle, responsible for much of the cardiovascular drive, are assumed to be transmitted in this compartment, blood pressure and heart rate could be affected by local or systemic variations in interstitial hydration. Using a special calf ergometer, eight male subjects performed rhythmic aerobic plantar flexions in a supine position with dependent calves for periods of 7 min. During exercise heart rate, blood pressure, oxygen uptake (VO2) and blood lactate concentrations were measured in two different tests, one before and after interstitial calf dehydration through limb elevation for 25 min, compared to the other, a control with unaltered fluid volume in a maintained working position. Impedance plethysmography showed calf volume to be stabilized in the control position. Leg elevation by passive hip flexion to 90 degrees resulted in a fast (vascular) volume decrease lasting less than 2 min, followed by a slow linear fluid loss from the interstitial compartment. Then, when returned to the control position, adjustment of vascular volume was completed within 2 min and exercise could be performed with dehydration remaining in the interstitium only. Cardiovascular response was identical at the start of both tests. However, exercising with dehydrated calves elicited a significantly larger increase in heart rate compared to the control, whereas VO2 was identical. The blood pressure response was shown to be only slightly enhanced. Structural interstitial features varying with hydration, most likely chemical or mechanical ones, may have been responsible for this amplification of signals. PMID- 1874239 TI - Cardiovascular response to static handgrip in trained and untrained men. AB - The influence of aerobic capacity on the cardiovascular response to handgrip exercise, in relation to the muscle mass involved in the effort, was tested in 8 trained men (T) and 17 untrained men (U). The subjects performed handgrip exercises with the right-hand (RH), left-hand (LH) and both hands simultaneously (RLH) at an intensity of 25% of maximal voluntary contraction force. Maximal aerobic capacity was 4.3 l.min-1 in T and 3.21 l.min-1 in U (P less than 0.01). The endurance time for handgrip was longer in T than in U by 29% (P less than 0.05) for RH, 38% (P less than 0.001) for LH and 24% (P less than 0.001) for RLH. Heart rate (fc) was significantly lower in T than in U before handgrip exercise, and showed smaller increases (P less than 0.01) at the point of exhaustion: 89 vs 106 beats.min-1 for RH, 93 vs 100 beats.min-1 for LH and 92 vs 108 beats.min-1 for RLH. Stroke volume (SV) at rest was greater in T than in U and decreased significantly (P less than 0.05) during handgrip exercise in both groups of subjects. At the point of exhaustion SV was still greater in T than in U: 75 vs 57 ml for RH, 76 vs 54 ml for LH and 76 vs 56 ml for RLH. During the last seconds of handgrip exercise, the left ventricular ejection time was longer in T than in U. Increases in cardiac output (Qc) and systolic blood pressure did not differ substantially between T and U, nor between the handgrip exercise tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874240 TI - Influence of ventilation of the face on thermoregulation in man during hyper- and hypothermia. AB - It has been suggested that a thermal countercurrent exchange may occur in the cerebral vascular bed of humans, thereby creating for the brain a state of relative thermal independence with regard to the rest of the body. However, worrying questions have arisen concerning this suggestion. Experiments were carried out on seven young male volunteers. Hyper- and hypothermic conditions were produced by immersion in water at 38.5 degrees C and 25 degrees C, respectively. During the last few minutes of immersion, the face was cooled or warmed by ventilation with a 200 l.min-1 air flow at 5 degrees C or 40 degrees C, respectively. Internal and peripheral temperatures were recorded. Blood flow in the anastomotic vessels between face and brain was measured by Doppler techniques associated with computerized frequency analysis. The general responses were as classically described, i.e. an increase in peripheral and central temperatures during immersion in the warm bath and a decrease in these variables in the cold bath. The reactions produced by cooling or warming the face were small and easily explained by the direct changes of the heat load they induced. Whatever the thermal conditions, the blood flow in the anastomotic vessels between the vascular bed of the face and that of the brain was never reversed. It was concluded that there was no experimental evidence for an efficient thermal counter-current exchange in the vascular bed of the human head. PMID- 1874241 TI - Plasma lipid concentrations in professional cyclists after competitive cycle races. AB - Plasma lipid concentrations were measured in professional cyclists at the beginning of the training season and both before the start and at the end of two cycle races of similar length (800 and 900 km in 6 days). Plasma concentrations of triglyceride, total and low density lipoprotein-cholesterol (LDL-C) and total cholesterol: high density lipoprotein-cholesterol (HDL-C) ratio were significantly lower and HDL-C concentrations significantly higher in cyclists compared to values in matched sedentary controls. At the end of the races, plasma concentrations of triglyceride and LDL-C were further reduced and HDL-C concentrations had increased compared to values at the start. At the end of the races, plasma concentrations of HDL-C were inversely correlated (r = -0.28, n = 45, P less than 0005) with triglyceride plasma concentrations. Body fat content, assessed as the sum of skinfold thicknesses was slightly reduced at the end of the race compared to the starting values. There was no significant correlation between skinfold thickness and plasma concentrations of HDL-C. Total plasma fatty acid concentrations were reduced and nonesterified fatty acids concentrations were increased at the end of the race compared to resting values. Consequently, the plasma concentrations of esterified fatty acids were significantly reduced after the race and there was a redistribution of the nonesterified fatty acids. The relative amounts of single fatty acids in the total fatty acid pool remained, however, remarkably constant. In conclusion, the results presented suggested that physical exercise, performed at the level of professional cyclists in a race, was an independent modifier of plasma lipid concentrations. PMID- 1874242 TI - Comparison in men of physiological responses to exercise of increasing intensity at low and moderate ambient temperatures. AB - In six male subjects the sweating thresholds, heart rate (fc), as well as the metabolic responses to exercise of different intensities [40%, 60% and 80% maximal oxygen uptake (VO2max)], were compared at ambient temperatures (Ta) of 5 degrees C (LT) and 24 degrees C (MT). Each period of exercise was preceded by a rest period at the same temperature. In LT experiments, the subjects rested until shivering occurred and in MT experiments the rest period was made to be of exactly equivalent length. Oxygen uptake (VO2) at the end of each rest period was higher in LT than MT (P less than 0.05). During 20-min exercise at 40% VO2max performed in the cold no sweating was recorded, while at higher exercise intensities sweating occurred at similar rectal temperatures (Tre) but at lower mean skin (Tsk) and mean body temperatures (Tb) in LT than MT experiments (P less than 0.001). The exercise induced VO2 increase was greater only at the end of the light (40% VO2max) exercise in the cold in comparison with MT (P less than 0.001). Both fc and blood lactate concentration [1a]b were lower at the end of LT than MT for moderate (60% VO2max) and heavy (80% VO2max) exercises. It was concluded that the sweating threshold during exercise in the cold environment had shifted towards lower Tb and Tsk. It was also found that subjects exposed to cold possessed a potentially greater ability to exercise at moderate and high intensities than those at 24 degrees C since the increases in Tre, fc and [1a]b were lower at the lower Ta. PMID- 1874243 TI - Athletes' pseudoanaemia. AB - To characterize the so-called pseudoanaemia of endurance-trained athletes, the plasma volume (PV), red cell volume (RCV) and total blood volume (TBV) of 12 male and 12 female athletes and 5 male and 5 female nonexercising controls were measured using 125I-labelled human serum albumin and 51Cr-labelled erythrocytes. The mean PV of the male athletes (52.8 ml.kg-1) was 37.5% higher than that of the controls (38.4 ml.kg-1), while the 18.1% increase measured in the female runners (51.5 ml.kg-1) over the controls (43.6 ml.kg-1) was a novel observation. Although the RCV was significantly greater (34.7%) in male athletes (32.6 ml.kg-1 vs 24.2 ml.kg-1 in the controls), a similar elevation (3.6%) was not found in the female athletes (25.9 ml.kg-1) compared to the sedentary women (22.8 ml.kg-1). This could have been due to iron-limited erythropoiesis because the RCV of the female athletes defined as clinically anaemic was markedly lower that of the nonanaemic women (P less than 0.05). The elevated plasma protein mass and concentration measured in the athletes partly accounted for their expanded PV. It was concluded that the decreased blood haemoglobin levels reported in the endurance athletes was largely a dilutional effect. PMID- 1874244 TI - Electrical stimulation of human forearm extensor muscles as an indicator of handgrip fatigue and recovery. AB - A set-up for percutaneous electrical stimulation of the forearm extensor muscles and measurement of wrist extension force is described. The frequency-force relationship and pulse duration-force relationship are described together with an experimental protocol showing that brief electrical test stimulations do not produce fatigue. In another set of experiments carried out a few weeks later, the subjects performed handgrip contractions: protocol A at 25% of maximal voluntary contraction (MVC) continuously until exhaustion, protocol B at 25% MVC intermittent (contraction + relaxation = 10 + 2 s) until exhaustion, and protocol C at 25% MVC intermittent until half the time to exhaustion. In all experiments, brief electrical stimulations were used to test the degree of fatigue during and up to 24 h after the experiments. There were marked changes in the force during stimulation at 20 and 100 Hz and these changes did not correlate with the increase in intramuscular temperature. Low frequency fatigue persisted for at least 24 h after protocol A and 1 h after protocols B and C. The significance of this is discussed and it is suggested that low frequency fatigue could be used as a sensitive indicator of muscle dysfunction after low and medium intensity exercise. PMID- 1874245 TI - The peak oxygen uptake of British children with reference to age, sex and sexual maturity. AB - The purposes of this study were to provide baseline data on the peak oxygen consumption (VO2) of British children, aged 11-16 years and to examine the peak VO2 of children in relation to their pubertal stage of development. The peak VO2 of 226 boys and 194 girls was determined during either treadmill running or cycle ergometry. The sexual maturity of 320 of the children was estimated using Tanner's indices. Peak VO2 increased with chronological age in both sexes and from about the age of 12 years boys exhibited significantly higher (P less than 0.05) values than girls. Boys' peak VO2 in relation to body mass was consistent over the age range studied and was superior (P less than 0.05) to girls' values at all ages. It appears that mass-related peak VO2 is independent of sexual maturity in both sexes. The more mature boys demonstrated a significantly higher (P less than 0.05) peak VO2 (1.min-1) than the less mature boys on both ergometers. The more mature girls demonstrated significantly higher (P less than 0.05) peak VO2 (1.min-1) than the less mature girls only on the cycle ergometer. On both ergometers the differences between the peak VO2 of the girls and boys were more pronounced in the mature children whether expressed in relation to body mass or not. Comparison of the results with earlier data drawn from smaller samples failed to provide evidence to suggest that British children's peak VO2 has declined in recent years. No study with which to compare our maturity peak VO2 data appears to be available. PMID- 1874246 TI - Maximal oxygen uptake and erythropoietic responses after training at moderate altitude. AB - Six well-trained male cross-county skiers trained for 7 days at 2700 m above sea level, their accommodation being at 1695 m. Blood samples for haemoglobin concentration [Hb], erythropoietin concentration [EPO] and reticulocyte count were collected before, during and after altitude exposure. Packed cell volume (PCV), red blood cell count (RBC), transferrin-iron saturation, mean red cell volume (MCV), mean corpuscular haemoglobin concentration (MCHC), maximal oxygen uptake, maximal achieved ventilation and heart rate were determined pre- and postaltitude exposure. The [EPO] increased significantly from pre-altitude (mean 36 mU.ml-1, SD 5) to maximal altitude values (mean 47 mU.ml-1, SD 3). The [Hb] had increased significantly above pre-altitude values (mean 8.8 mmol.l-1, SD 0.5) on day 2 (mean 9.1 mmol.l-1, SD 0.4) and day 7 (mean 9.4 mmol.l-1, SD 0.4) at altitude and on day 4 postaltitutde (mean 9.2 mmol.l-1, SD 0.4). The reticulocyte counts had increased significantly above pre-altitude values (mean 6%, SD 3%) on day 3 at altitude (mean 12%, SD 8%) and day 4 postaltitude (mean 10%, SD 5%). The RBC counts had increased on the 4th postaltitude day. The transferrin-iron saturation had decreased below pre-altitude values (mean 23%, SD 4%) on day 4 postaltitude (mean 14%, SD 5%) and had increased on day 11 postaltitude (mean 22%, SD 7%). There were no significant changes in MCV, MCHC, PCV, maximal oxygen uptake and maximal achieved ventilation, and heart rate pre- to postaltitude. These observations demonstrated an erythropoietic response to the altitude training which was not sufficient to increase the postaltitude maximal oxygen uptake. PMID- 1874247 TI - Plasma accumulation of hypoxanthine, uric acid and creatine kinase following exhausting runs of differing durations in man. AB - During exhausting exercise adenylate kinase in the muscle cells is activated and a degradation of adenosine 5'-diphosphate occurs. Consequently, degradation products of adenosine 5'-monophosphate including hypoxanthine and uric acid, accumulate in plasma. The aim of this study was to compare the concentration changes of hypoxanthine and uric acid in plasma following running of varying duration and intensity. In addition, plasma creatine kinase activity was measured to assess the possible relationship between metabolic stress and protein release. Four groups of competitive male runners ran 100 m (n = 7), 800 m (n = 11), 5000 m (n = 7) and 42,000 m (n = 7), respectively, at an exhausting pace. Subsequent to the 100 m event (mean running time 11 s) plasma concentrations of hypoxanthine and uric acid increased by 364% and 36% respectively (P less than 0.05), indicating a very high rate of adenine nucleotide degradation during the event. Following the 800-m event (mean running time 125 s), hypoxanthine and uric acid concentrations had increased by 1598% and 66%, respectively (P less than 0.05). Both the events of longer duration, 5000 m and 42,000 m, also caused a significant increase in plasma concentration of hypoxanthine (742% and 237% respectively, P less than 0.05) and plasma uric acid (54% and 34% respectively, P less than 0.05). Plasma activities of creatine kinase were significantly increased at 24 h only following the 5000 m and 42,000 m events (64% and 1186% respectively, P less than 0.05). Changes in plasma creatine kinase activity showed no correlation with changes in plasma concentration of either hypoxanthine or uric acid for the 5000 m and 42,000 m events (r = 0.00-0.45, P greater than 0.05). PMID- 1874249 TI - Selective medium for isolation of Arcanobacterium haemolyticum and Streptococcus pyogenes. AB - Sheep blood agar using tryptic soy agar base and containing 3.5% sodium chloride was found to facilitate isolation of Arcanobacterium haemolyticum and improve isolation of Voges-Proskauer negative group A (Streptococcus pyogenes) and group C and G beta-haemolytic streptococci. Commensal oropharyngeal flora such as viridans streptococci, Neisseria species, non-haemolytic streptococci and beta haemolytic streptococci not belonging to groups A, B, C or G were significantly inhibited. PMID- 1874248 TI - Diagnosis of Lyme borreliosis by an enzyme immunoassay detecting immunoglobulin G reactive to purified Borrelia burgdorferi cell components. AB - An enzyme immunoassay (EIA) developed for the diagnosis of Lyme borreliosis was tested for its specificity and sensitivity in detecting IgG antibodies in patients at various stages of the disease. The EIA is based on a detergent extract of Borrelia burgdorferi which contains 12 proteins of defined molecular weights from Borrelia burgdorferi. The assay showed a specificity of 100% in control sera from 64 healthy individuals, using a cut-off optical density value of 0.13 (means +2- 3 SD). The sensitivity was 100% using sera from 22 Swedish patients with late stage Lyme borreliosis and 43% using sera from 30 patients with the initial stage of the disease. The reactivity of the sera against whole cell preparations, the outer surface proteins OspA and OspB, and the flagella of Borrelia burgdorferi was also tested and compared with the EIA. No cross reactivity with treponemal antigens was observed when using the EIA. PMID- 1874250 TI - Lipase versus teichoic acid and alpha-toxin as antigen in an enzyme immunoassay for serological diagnosis of Staphylococcus aureus infections. AB - Titres of IgG antibodies to Staphylococcus aureus lipase were analysed in 448 sera from patients suspected of having Staphylococcus aureus infections and the results compared to those for the routinely used staphylococcal antigens teichoic acid and alpha-toxin. The results indicated that determination of serum antibodies to lipase is a sensitive assay for serological diagnosis of staphylococcal infections and increased sensitivity may be achieved by selection of optimal antigen combinations. PMID- 1874251 TI - Isolation of Agrobacterium radiobacter from a central venous catheter. AB - A case of septicemia caused by Agrobacterium radiobacter is reported in a patient undergoing chemotherapy treatment who had recently been neutropenic. Agrobacterium radiobacter was isolated from the Hickman line blood culture. The patient responded favorably to removal of the Hickman catheter and treatment with amikacin and piperacillin. The molecular and biochemical characteristics of the isolate are presented. PMID- 1874252 TI - Comparison of five commercial western blot kits for detection of human immunodeficiency virus 1. AB - Twenty-two human immunodeficiency virus 1 (HIV-1) enzyme immunoassay (EIA) reactive and two non-reactive patient specimens were analyzed using five commercially available HIV-1 Western blot kits. The percentage of HIV-1 bands detected by each kit was recorded. The differences between pairs of kits were not found to be statistically significant at the 0.05 level. All EIA reactive specimens were reconfirmed as reactive by each Western blot kit tested. PMID- 1874253 TI - Fluconazole therapy of candidal native valve endocarditis. PMID- 1874254 TI - Presence of spiral bacteria ("Gastrospirillum hominis") in the gastric mucosa. PMID- 1874255 TI - Direct detection of Pneumocystis carinii in fresh bronchoalveolar lavage specimens. PMID- 1874256 TI - Ventricular late potentials in patients with and without inducible sustained ventricular tachycardia: a combined analysis in the time and frequency domain. AB - Time and frequency of signal-averaged electrocardiograms from 51 patients and 19 normal subjects were studied. A new filter device was designed to facilitate the analysis of the complete QRS complex, particularly the high-frequency components. All patients underwent electrical programmed stimulation (EPS) with up to three extra stimuli. In 29 patients, sustained ventricular tachycardia (VT) was inducible (group A), whereas in 22, sustained VT could not be elicited (group B). Between A and B, we compared several variables from the signal-averaged ECG as well as clinical data. The variables that differed between the two groups (P less than 0.01) were entered into a logistic regression model to determine which ones could most reliably predict the outcome of EPS. A combination of three variables (number of minima and maxima in the terminal QRS; third of four areas of equal length, divided by the total area below the QRS; maximum of the frequency spectre in the terminal QRS) could predict the inducibility of sustained VT with 82.8% sensitivity and 86.4% specificity. PMID- 1874257 TI - Determination of left ventricular systolic wall thickness by digital subtraction angiography. AB - The accuracy of digital subtraction angiography (DSA) for determination of left ventricular (LV) systolic wall thickness and muscle mass was evaluated in 20 patients (mean age 50 +/- 11 years). Conventional LV angiograms were digitized and subtracted using a combined subtraction mode ('mask mode' and 'time interval difference' subtraction). Wall thickness and muscle mass were determined at end diastole, after the first- and second-third of systole and at end-systole. M-mode echocardiography (Echo), which was obtained from beam selection of the two dimensional echocardiogram and conventional angiography (LVA), served as reference techniques. Angiographic LV wall thickness and muscle mass were determined according to the technique of Rackley in both, right (RAO) and left (LAO) anterior oblique projections, whereas echocardiographic wall thickness was measured just below the mitral valve orthogonal to the posterior wall (= LAO equivalent). Percent wall thickening was calculated in all patients. LV end diastolic wall thickness and muscle mass correlated well between DSA and LVA (LV end-diastolic wall thickness in LAO projection r = 0.72, biplane LV end-diastolic muscle mass r = 0.83), LV end-systolic wall thickness (1.44 vs 1.33 cm, P less than 0.05) and percent wall thickening (52 vs 42%, P less than 0.05) compared favourably between echocardiography and DSA but was significantly larger when echocardiographically measured than with DSA (LAO projection). DSA and echocardiography showed a good correlation in regard to LV end-diastolic and end systolic wall thickness (correlation coefficient r = 0.89, standard error of estimate SEE = 0.15 cm or 13% of the mean value).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874258 TI - Contribution of platelets and platelet-activating factor (PAF) to the arrhythmogenic, haemodynamic and necrotic effects of acute myocardial ischaemia. AB - The effects of alterations in platelet activity on arrhythmias, haemodynamics and extent of necrosis during coronary ligation for 30 min were assessed in rabbits. Reduction of platelet counts to less than 1% of control by intravenous injection of platelet antiserum (1 ml kg-1 i.v.) reduced the volume of necrosed tissue from 23 +/- 2% to 15 +/- 1%, P less than 0.01 (expressed as % of total LV) and attenuated the hypotensive effect of ischaemia. Pretreatment with the platelet activating factor (PAF) antagonist BN 52021 also attenuated the hypotension and necrosis caused by coronary ligation 23 +/- 2% vs 14 +/- 1%, P less than 0.01. Pretreatment with the thromboxane antagonist CGS 13080 attenuated the hypotensive response to ischaemia but had only a very small effect on the area of necrosis. Administration of PAF at 10 min following coronary ligation markedly increased the volume of necrosed tissue 36 +/- 2%, P less than 0.01 and caused VF and haemodynamic collapse in 10 out of 12 animals. Pretreatment with platelet antiserum or the PAF antagonist BN 52021 reversed this effect of PAF. Pretreatment with CGS 13080 attenuated the marked hypotensive effect of PAF but failed to reverse its necrotic or arrhythmogenic effects. These findings indicate that platelet activation contributes to the necrosis and hypotension following coronary ligation and that platelet-activating factor may contribute to this. The ameliorating effects of platelet antiserum or BN 52021 support the concept that inhibition of platelet activity may have a useful role in the treatment of acute myocardial infarction. PMID- 1874259 TI - Comparison of different orthogonal systems in high resolution ECGs and the significance of the number of averaged beats in detecting late potentials. AB - For non-invasive detection of late potentials in the signal-averaged electrocardiogram (SAECG) most studies use modified orthogonal leads. In the present study the significance of three different lead systems for the detection of late potentials was examined. SAECGs were recorded at five different (32, 64, 128, 256, and 512) numbers of averaged beats in 24 patients with ventricular tachycardia after myocardial infarction and in 76 normal subjects. The original Frank leads and two different modified orthogonal vector lead systems were used. There was no clinical difference between the three orthogonal systems in sensitivity and the difference in specificity (P less than 0.01) seemed to be primarily related to differences in noise content. When the vector systems were compared at equally low noise levels of 0.47-0.50 microV, the apparent differences in specificity between the vector systems disappeared. At decreasing noise levels the sensitivity increased, at the cost of a loss in specificity which at very low noise levels was out of proportion with the gain in sensitivity. A modified approach with a fixed threshold noise level to determine the QRS endpoint is suggested. PMID- 1874260 TI - The effect of cardiac catheterization upon management of advanced aortic and mitral valve disease. AB - We assessed the incremental effect of cardiac catheterization upon the management of 93 adult patients with aortic and/or mitral valve disease, referred for surgical consideration. There were 52 patients with aortic valve disease, 29 with mitral valve disease and 12 with aortic and mitral valve disease. Prior to cardiac catheterization, a detailed unblinded ultrasound assessment of each valve was made utilizing 2D and Doppler ultrasound. Based upon the ultrasound result and the clinical assessment, the patient's cardiologist recorded a grading of valve severity and a management decision for each valve. Following catheterization and coronary angiography, the cardiologist repeated the gradings of valve severity and recorded a final management decision. After catheterization, management changed in nine patients and was unchanged in 84. Reasons for management change included differences between echocardiographic and catheterization assessment of valvular regurgitation (three patients), information on coronary anatomy (two patients), minor differences in assessed aortic valve area (one patient) and left ventricular function (one patient), and confirmation of ultrasound findings where clinical and ultrasound findings had been conflicting before catheterization (two patients). Both mitral and aortic valve disease were present in the three patients in whom management changed as a result of significant differences between echocardiography and catheterization assessment of valvular regurgitation. Management was unchanged in the 16 patients with isolated mitral stenosis. In this study, a combination of clinical and noninvasive assessment including Doppler echocardiography, resulted in a reliable evaluation of valvular disease in a large majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874261 TI - Electrocardiographic determinants of efficacy of 8-Joule shocks for ablation of the atrioventricular node. AB - Factors determining the success of a single, low-energy, direct current-shock to achieve chronic complete heart block were studied in a consecutive group of 14 patients. A shock of 8 J was delivered by a modified device (Sirecust BS1, Siemens). If the first shock did not produce persistent complete block, multiple shocks were given. Standard 6 French U.S.C.I. catheters were used for all procedures. Chronic complete heart block was achieved with a single shock in six cases (43%; Group I); in eight others multiple shocks were needed (Group II). Neither polarity of the bipolar and of the distal His bundle recording nor the presence of sinus rhythm before the first shock were important factors to predict the outcome. The amplitude of the first recording of the bipolar His electrogram was 225 +/- 55 microV in Group I and 138 +/- 105 microV in Group II (P = 0.029). The duration of the HV interval before the first shock was 55 +/- 12 ms in Group I and 45 +/- 11 ms in Group II (NS). It is concluded that complete permanent heart block can be achieved with a single 8-J shock in 43% of the patients. The long-term success (follow-up at least 1 month, with a range of 1 to 8) of a single 8-J shock is predicted by a large amplitude of the bipolar and distal unipolar His bundle deflection, but not by its polarity or the HV interval. PMID- 1874262 TI - Comparison of a rehabilitation programme, a counselling programme and usual care after an acute myocardial infarction: results of a long-term randomized trial. P.RE.COR. Group. AB - One hundred and eighty-two male post myocardial infarction patients under 65 years old were randomized 30 to 60 days after the acute event into a 6-week rehabilitation programme (RP), a counselling programme without exercise training training (CP) and usual care (UC). Follow-up visits and exercise tests on a bicycle ergometer were performed 2, 12 and 24 months after randomization. Baseline characteristics were identical in the three groups. The percentage of patients reaching the maximal heart rate at exercise test was higher in the RP group even after 2 years (UC = 24%, CP = 13%, RP = 50%, P = 0.001). The number of deaths at 2 years was respectively 4, 5 and 0 in the UC, CP and RP groups (P = 0.08). If UC and CP groups are combined and tested against RP the difference is statistically significant (P = 0.03). Reinfarction rates were similar in the three groups (UC = 10%, CP = 7%, RP = 7%). This study confirms that a rehabilitation programme seems worth recommending in young patients with uncomplicated myocardial infarction. PMID- 1874263 TI - Dromotropic effects of oral theophylline in patients with atrial fibrillation and a slow ventricular response. AB - Theophylline increases sinus rate, but as yet its use has not been investigated in patients with chronic atrioventricular conduction disturbances. Resting electrocardiogram, 24-h Holter recording and treadmill test were performed in 17 patients with chronic atrial fibrillation and a slow ventricular response not related to drugs (age: 75 +/- 8 years). Then slow-release theophylline was administered (700 mg daily) and after 5 days these investigations were repeated with the same methods. Theophylline increased mean resting heart rate (51 +/- 6 versus 67 +/- 13 beats.min-1, P less than 0.01), mean 24-h heart rate (51 +/- 6 versus 68 +/- 14 beats.min-1, P less than 0.01) and minimal 24-h heart rate (32 +/- 6 versus 42 +/- 11 beats.min-1, P less than 0.01). Cardiac pauses greater than 2.5 s were present in 13 patients during control recording; after theophylline they disappeared in 11 and markedly decreased in the remaining two. The longest R-R interval decreased in all patients (3218 +/- 943 versus 2121 +/- 518 ms, P less than 0.01). The daily number of wide QRS complexes increased in 16 out of 17 patients (428 +/- 752 versus 1146 +/- 1464 ms, P less than 0.01). Exercise heart rate, evaluated at the end of first and second stage, was higher after theophylline than during control test (P less than 0.01). These data suggest that oral theophylline can represent a valid therapy in most patients with atrial fibrillation and a slow ventricular response. PMID- 1874264 TI - Suppression of Torsades de Pointes with verapamil in patients with atrio ventricular block. AB - Experimental data have suggested a relation between Torsades de Pointes and early post-depolarization (EPD). We have studied the effect of intravenous verapamil in three patients with atrioventricular block (AVB) and Torsades de Pointes (TP), to obtain indirect evidence of slow membrane channel involvement in the TP mechanism. In two cases TP were completely suppressed and in one there was marked, albeit partial, suppression. In two cases verapamil did not shorten QT, while in the third suppression verapamil was related to junctional escape acceleration and QT shortening. In one of the cases where QT was not changed, the abolition of long pauses may have played a role in TP suppression. The affect of verapamil on TP in our patients is consistent with a combination of mechanisms, including direct membrane effects (EPD inhibition) and junctional pacemaker acceleration. Verapamil might be of therapeutic value in this clinical setting. PMID- 1874265 TI - Agranulocytosis associated with aprindine and other antiarrhythmic drugs: an epidemiological approach. AB - The risk of agranulocytosis associated with anti-arrhythmic drugs has been assessed by studying previous drug exposure of all cases collected through a multicentre surveillance network in a defined geographical area during the period 1980-1988. One hundred and eighty-one patients with agranulocytosis (less than 500 granulocytes mm-3 at least in two different blood counts) were interviewed with a structured questionnaire. Eight cases attributable to anti-arrhythmic drugs were identified, all of them related to aprindine. Data on the consumption of several anti-arrhythmic drugs were identified, all of them related to aprindine. Data on the consumption of several anti-arrhythmic drugs (amiodarone, aprindine, quinidine, propafenone) were obtained in order to estimate the risk of agranulocytosis related with the previous use of these drugs. A relevant risk was identified only for aprindine, of the order of two cases per 1000 patient-years. Our data suggest that the risk of agranulocytosis associated with aprindine is lower than previously found. PMID- 1874266 TI - Long-term results of coronary angioplasty for single vessel, proximal, left anterior descending disease. AB - The acute and long-term results of coronary angioplasty in 295 patients with isolated, proximal left anterior descending coronary stenosis are reported. The angiographic success rate was 83.4% overall, but 90.5% for non-occluded arteries treated since 1985. Clinical success at hospital discharge was achieved in 79.7%. The median duration of follow-up was 2.9 years and vital status was established in 99.7% at census. Cumulative 5-year cardiac survival was 96.2% after successful angioplasty and 95.6% for all patients. Five-year freedom from all cardiac events including cardiac death, myocardial infarction and repeat intervention was 73.8% amongst successfully treated patients, and 63.0% for all patients. After angioplasty, patients had less angina, required less anti-anginal medication and were more likely to be in gainful employment. Our data indicate that coronary angioplasty is an effective long-term treatment for selected patients with single vessel disease involving the proximal left anterior descending coronary artery. PMID- 1874267 TI - Long-term follow-up after attempted angioplasty of saphenous vein grafts: the Thoraxcenter experience 1981-1988. AB - Between 1981 and 1988, 107 percutaneous transluminal coronary angioplasty (PTCA) procedures, including repeat PTCA, were performed in 84 patients with previous coronary artery bypass grafting (CABG). Fifty-nine patients underwent a first angioplasty of the vein graft alone, and 25 underwent a first PTCA of the graft and one or more native vessels. Seventeen patients underwent two procedures, four patients three procedures and one patient four procedures. In 84 first angioplasties, 133 lesions were attempted; 40 lesions in native vessels and 93 graft lesions (28 ostial stenoses, 33 shaft stenoses, and 32 stenoses at the distal anastomosis). Three patients died during their hospital stay. Two patients underwent emergency CABG. Seven patients sustained an acute myocardial infarction (AMI), among whom five underwent a PTCA of an occluded vessel. The clinical primary success rate per patient was 82%. After five years, 70% of patients were alive. At a median follow-up of 2.1 years, 41% of patients were alive and event free (no AMI, no repeat CABG, no repeat PTCA). Symptomatic improvement was maintained in 36% of patients. Angioplasty of grafts may be an alternative to re operation in selected patients with previous bypass surgery. PMID- 1874268 TI - 2,3-butanediol in experimental myocardial ischaemia in pigs. AB - To investigate the role of 2,3-butanediol in myocardial ischaemia we analysed this compound in pig's myocardium and blood. Ischaemia was induced by ligation of a coronary artery. In the first study we found significantly higher levels of 2,3 butanediol in the homogenate of ischaemic myocardium than in non-ischaemic myocardium. The lactate concentration was also significantly elevated. In the second study, where ischaemia was similarly induced, and where reperfusion was achieved by re-opening the ligated coronary artery after 20 min, 2,3-butanediol in peripheral blood was found to increase significantly. In the pigs in which the coronary artery was not re-opened, the 2,3-butanediol level in peripheral blood was unchanged. We conclude that in pigs' anaerobic myocardia accumulation of 2,3 butanediol occurs; if the myocardium is reperfused this metabolite also appears in the blood. PMID- 1874269 TI - Nitrate tolerance--can it be prevented? AB - Tolerance develops during therapy with all organic nitrates, particularly when dosing strategies are designed to provide therapeutic effects throughout 24 h. Such tolerance can be demonstrated by assessing haemodynamic, anti-anginal and anti-ischaemic effects during therapy. The mechanism of nitrate tolerance is not completely understood. Tolerance may be related to depletion of reduced sulfhydryl groups in vascular smooth muscle with resultant reduction in nitric oxide production, adenylate cyclase activation and cyclic guanosine monophosphate (GMP) production. Nitrate exposure also activates counter-regulating influences which lead to fluid retention and augmented vasoconstrictor effects. Intermittent nitrate therapy avoids the problem of tolerance by providing a period of washout. Controlled-release formulations of oral nitrates providing a period of low nitrate exposure should prevent tolerance. This has been documented by studies with a controlled-release formulation of isosorbide-5-mononitrate. PMID- 1874270 TI - Why use a nitrate in 1990? AB - Nitrates are beneficial because they combine coronary and noncoronary effects. They have proven clinical efficacy, relieving symptoms and documented evidence of ischaemia. They can be given to patients by multiple routes and can be easily combined with other anti-ischaemic drugs including aspirin, heparin, calcium antagonists and beta-blockers. PMID- 1874271 TI - Is there an optimal prophylactic nitrate therapy? AB - Nitrates have a place in the prophylactic treatment of patients with angina pectoris. Their efficacy is not in doubt. However, there may be some practical problems associated with their use, such as unreliable absorption, short duration of action, treatment-induced headache, development of nitrate tolerance and a suggested rebound phenomenon observed during intermittent dosing. This article discusses how many of these problems may be solved by selection of formulation as well as nitrate compound. Thus, the development of a controlled-release formulation producing sufficiently high nitrate plasma concentrations during part of the day, followed by a low nitrate level rather than a nitrate-free interval, seems to have the potential to prevent both nitrate tolerance and rebound phenomenon. This system would also offer a sufficiently long duration of action with a convenient once-daily dose regimen. PMID- 1874272 TI - Endogenous nitrates--implications for treatment and prevention. AB - The endothelium-derived relaxing factor (EDRF) is nitric oxide (NO) or a closely related nitrosothiol derivative, and is formed from the amino acid, L-arginine. NO is rapidly inactivated locally, released into the blood stream and instantly destroyed by haemoglobin. EDRF-NO and NO generated from vasodilator nitrates work by activation of soluble guanylate cyclase, elevating cyclic guanosine monophosphate (GMP) levels to cause vasodilatation and inhibition of platelet aggregation. Endothelium-dependent vasodilatation is attenuated in hypertension, atherosclerosis and diabetes through either loss of endothelium or deficient formation of EDRF-NO. In these conditions exogenous nitrates may substitute for a failing endogenous mechanism. PMID- 1874273 TI - Nitrate therapy: is there an optimal substance and formulation? AB - Nitrate therapy has been shown to be beneficial for the treatment of coronary artery diseases and a number of chemical entities and their respective pharmaceutical formulations are available for clinical use. In this report, the performance of these nitrate drug/formulation combinations is discussed in terms of the relative onset of action, duration of action, tolerance properties/regeneration of reactivity and patient acceptance. A pharmacodynamic action scheme is presented and this allows a systematic assessment of how changes in the nitrate and/or formulation may impact on therapeutic activity. Data suggest that several sustained-release preparations of various nitrates can provide protection against exercise-induced angina for about 12 h on repeated dosing, provided a 'nitrate-free' or 'nitrate-poor' interval is also instituted. The 'ideal' nitrate substance and formulation, which theoretically can provide around-the-clock protection, is not yet available. PMID- 1874274 TI - Central effects of muscarinic agonists and antagonists on hippocampal theta rhythm and blood pressure in the anaesthetised rat. AB - The in vivo central effects of a range of full and partial muscarinic receptor agonists have been investigated on hippocampal theta rhythm and blood pressure. In the isoflurane-anaesthetised rat, pretreated with N-methylscopolamine, i.v. administration of arecoline, oxotremorine, arecaidine propargyl ester, aceclidine and pilocarpine produced dose-dependent increases in the frequency of hippocampal theta rhythm and blood pressure, with an order of potency of arecoline = oxotremorine = arecaidine propargyl ester greater than aceclidine greater than or equal to pilocarpine. To increase theta wave frequency, pilocarpine showed a low maximum response and possessed antagonist activity against arecoline, indicating that pilocarpine was acting as a partial agonist. AF102B failed to alter blood pressure or theta rhythm. Intraventricular injections of scopolamine and the M1 receptor-selective antagonist, pirenzepine, produced dose-dependent antagonism of the enhanced theta wave frequency and hypertensive response produced by arecoline. The differences in antagonist potency for the two responses was less than 6-fold, which indicated that both the increase in hippocampal theta wave activity and increase in blood pressure may have been mediated through muscarinic receptors of the M1 subtype. Further studies using a wider range of antagonists will be required to confirm this conclusion. PMID- 1874275 TI - Selective protection by adenosine receptor agonists against DMCM-induced seizures. AB - The anticonvulsant actions of the adenosine receptor agonists, 1 phenylisopropyladenosine, 2-chloroadenosine and cyclohexyl-adenosine, against DMCM (methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate)-induced seizures in mice were studied with an infusion technique. 2-Chloroadenosine and cyclohexyladenosine were active at 1 mg/kg whereas 1-phenyl-isopropyladenosine was active at 0.03 mg/kg given i.p. At 10 mg/kg, 1-phenylisopropyladenosine was only weakly active against pentylenetetrazol-induced seizures and not active against bicuculline-induced seizures. The selective effect of 1 phenylisopropyladenosine against DMCM-induced seizures suggests that adenosine receptor agonists may allosterically counteract the negative modulating effect of DMCM on GABA coupling to the chloride channel. This indicates that adenosine receptors may have a physiological function within the GABA/benzodiazepine receptor complex in the brain. PMID- 1874276 TI - Effects of HA1077, a protein kinase inhibitor, on myosin phosphorylation and tension in smooth muscle. AB - We examined the effects of HA1077, a potent inhibitor of protein kinases in vitro, on the relationship between tension and myosin-light chain (MLC20) phosphorylation in the initial phase of contraction of the rabbit aorta. The dose response curve of HA1077 for MLC20 phosphorylation was to the left of the tension curve produced by 40 mM K+. In contrast, the potassium dose-response (15-100 mM) curves for tension and MLC20 phosphorylation were virtually identical. The nifedipine dose-response (1-3000 nM) curves for tension and MLC20 phosphorylation after 40 mM K(+)-stimulation were much the same. HA1077 inhibited the contraction induced by 30 microM prostaglandin F2 alpha (ED50 = 50 microM). Stimulation with prostaglandin F2 alpha induced both mono (MLC-P) and diphosphorylation (MLC-P2) of MLC20. In the presence of various concentrations of HA1077 (1-300 microM), the dose-response curves for MLC-P and MLC-P2 were also to the left of the tension curve. HA1077 inhibited MLC-P2 (ED50 less than microM) more effectively than it inhibited MLC-P (ED50 = 2.1 microM). These observations indicate that the relationship between tension and MLC20 phosphorylation involves inhibition of protein kinases by HA1077. The mechanism underlying the formation of MLC-P2 induced by prostaglandin F2 alpha may differ from that underlying MLC-P formation. PMID- 1874277 TI - Acetylcholine vasodilation of resistance vessels in vivo may not entirely depend on newly synthesized nitric oxide. AB - Blood flow was measured in denervated hind limbs of pentobarbital-anesthetized cats. Intravenous NG-methyl-L-arginine, 3-30 mg/kg did not affect the magnitude or duration of vasodilation produced by intra-arterial acetylcholine. Intra arterial NG-methyl-L-arginine induced hind limb vasoconstriction and reduced the duration but not the magnitude of the acetylcholine vasodilator response. The results suggest that acetylcholine-induced hind limb vasodilation may not entirely depend on newly synthesized nitric oxide. PMID- 1874278 TI - Angiotensin II stimulates angiogenesis in the chorio-allantoic membrane of the chick embryo. AB - Angiotensin II was applied daily in doses of 67 or 670 ng to a section of the chick embryo chorio-allantoic membrane from day 7 to day 14 after fertilization of the eggs. During this one-week period, it caused a significant, dose-dependent increase in the vascular density index. The increase obtained with 670 ng daily was comparable to that after daily administration of 1.7 micrograms adenosine, a known stimulator of angiogenesis. The data suggest a possible role for angiotensin II as a mediator of vascular growth. PMID- 1874279 TI - Different regulation of vascular tone by angiotensin II and endothelin-1 in rat aorta. AB - The effects of moderate cooling and of phenylarsine oxide on the contraction induced by two vasoactive peptides, angiotensin II (AII) and endothelin (ET-1), were investigated on endothelium-free rings of rat aortas. At 37 degrees C, the contraction induced by AII (0.1 microM) was transient. This decline in tension is unlikely to be due to rapid degradation of AII. In contrast, ET-1 (10 nM) induced a slowly developing and sustained contraction similar to the one observed with phorbol 12-13 dibutyrate (PDB, 22 nM). Moderate cooling (25 degrees C) significantly potentiated and prolonged the effect of AII but reduced the velocity of the ET-1 and PDB contraction, although the rate of the phenylephrine (1 microM) response remained unchanged. Phenylarsine oxide (100 microM) reduced the decline in tension in response to AII but inhibited the contraction elicited by ET-1 and PDB. In rings incubated in calcium-free medium (37 degrees C), AII induced a phasic contraction. This was followed by a second phasic contraction after calcium (2.5 mM) had been restored to the bath. The intensity of this second contraction decreased as the time between AII and calcium injection increased. This method, using regression analysis, permitted us to determine the time taken to reduce the contraction by half (4.8 min; r: 0.96), which may reflect the half-time of receptor sequestration. In calcium-free medium, the contractions induced by ET-1 and PDB were slow and sustained. Thus, rapid AII receptor internalization leads to a short-term regulation of vascular tone whereas activation of protein kinase C by ET-1 may induce a long-term regulation. PMID- 1874280 TI - Block of the transient inward current by R56865 in guinea-pig ventricular myocytes. AB - Single myocytes isolated from the guinea-pig ventricle were used under voltage clamp conditions to study the activity of a newly developed drug, R56865, a benzothiazolamine derivative, against digitalis toxicity. Multicellular Purkinje preparations were used in some experiments. The drug blocked the transient inward current (TI) with an apparent KD of 7.5 X 10(-8) M. The blockade was not due to a direct effect on the Na+, Ca2+ exchange current or on the non-selective cation current, the two components of TI. Blockade of TI was accompanied in time with inhibition of after-contractions, which suggests that the drug has an effect on Ca(2+)i transients. At concentrations effective on TI the drug did not block Ca2+ currents or Na+ currents; however the Na+ current was inhibited after the cells had been pretreated with DPI 201-106. It is suggested that the inhibitory effect on TI may be due to an effect on the release of Ca2+ from the sarcoplasmic reticulum or to a reduction in Ca2+ overload via blockade of the Na+ channel. PMID- 1874281 TI - The antihypertensive effect of 2-alkynyladenosines and their selective affinity for adenosine A2 receptors. AB - We examined the affinity for adenosine receptors and the antihypertensive effects of 2-alkynyladenosines, especially 2-hexynyladenosine (2-H-Ado) and 2 octynyladenosine (2-O-Ado). The order of decreasing affinity of 2-H-Ado, 2-O-Ado, and other agonists tested for A1 receptors was N6-cyclopentyladenosine (CPA) greater than N6-cyclohexyladenosine (CHA) greater than N6-R phenylisopropyladenosine (R-PIA) greater than 2-chloroadenosine (CADO) = 5'-N ethylcarboxamideadenosine (NECA) greater than N6-S-phenylisopropyladenosine (S PIA) greater than 2-H-Ado greater than 2-O-Ado greater than 2 phenylaminoadenosine (CV-1808), and that for A2 receptors was 2-H-Ado greater than 2-O-Ado = NECA greater than CADO greater than CV-1808 greater than R-PIA greater than CPA greater than CHA greater than S-PIA. The Ki values of 2-H-Ado and 2-O-Ado for [3H] NECA binding to A2 receptors were 4.1 and 12.1 nM, respectively, and those for [3H]CHA binding to A1 receptors were 146 and 211 nM, respectively: the affinity of 2-H-Ado and 2-O-Ado for A2 receptors was about 36- and 17-fold higher than their affinity for A1 receptors. Injection of 2-H-Ado and 2-O-Ado (0.03-100 micrograms/kg) decreased the blood pressure of anaesthetized spontaneously hypertensive rats (SHR). A slight decrease in heart rate was observed after i.v. injection of 100 micrograms/kg 2-H-Ado and 2-O-Ado. A potent and long-lasting antihypertensive effect was also observed after oral administration of 2-H-Ado and 2-O-Ado to conscious SHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874282 TI - A non-immunogenic myasthenia gravis model and its application in a study of transsynaptic regulation at the neuromuscular junction. AB - A non-immunological model for myasthenia gravis was developed in rats: 'toxin induced myasthenia gravis'. Rats were injected once every 48 h with 3-5 micrograms alpha-bungarotoxin for periods of up to 5 weeks. This treatment caused weakness, especially of facial muscles. Respiration, however, was unaffected. Miniature endplate potentials and 125I-alpha-bungarotoxin binding in the extensor digitorum longus muscles were severely reduced. Acetylcholine release evoked by electrical and chemical (50 mM KCl) stimulation was higher in diaphragms from alpha-bungarotoxin-treated rats than in those from control animals. Histological investigation of the tibialis anterior muscle provided no evidence that the endplates were enlarged. It is concluded that the activity of acetylcholine receptors influences the rate of transmitter release in the neuromuscular junction and it is suggested that a transsynaptic regulation process may be active in myasthenia gravis. The present animal model for myasthenia gravis seems very suitable for studying such a regulation of transmitter release. PMID- 1874283 TI - The neutral endopeptidase-24.11 (enkephalinase) inhibitor, SCH 32615, increases dopamine metabolism in the nucleus accumbens of the rat. AB - SCH 32615 is a novel inhibitor of the enzyme, neutral endopeptidase (NEP, E.C. 3.4.24.11), the so called 'enkephalinase', which plays a functional role in the degradation of [Met5]- and [Leu5]enkephalin. The present study was designed to assess whether SCH 32615 is able to modify the activity of dopaminergic neurons as reflected by changes in the content of the major dopamine metabolite, dihydroxyphenylacetic acid (DOPAC), in three different areas of the rat brain: the nucleus accumbens, the striatum, and the prefrontal cortex. When administered at analgesically active doses (1-100 mg/kg s.c., 60 min before killing), SCH 32615 induced a dose-dependent increase in dopamine metabolism in the nucleus accumbens but was ineffective in the striatum and in the prefrontal cortex. This effect appears to be mediated via opioid receptors, since it was completely prevented by naloxone (5 mg/kg s.c.). The increase in DOPAC content in the prefrontal cortex elicited by foot-shock was unaffected by pretreatment with SCH 32615. In the nucleus accumbens, dopamine metabolism was increased to the same extent by foot-shock and SCH 32615 administered separately, but these effects were not additive, suggesting that SCH 32615 and foot-shock act via a common mechanism. Taken together, these results support the hypothesis that inhibition of the in vivo degradation of enkephalins induced by the systemic administration of SCH 32615 increases the enkephalinergic tone in the central nervous system and thereby activates the mesolimbic dopaminergic neurons. PMID- 1874284 TI - Oxyhaemoglobin increases the production of endothelin-1 by endothelial cells in culture. AB - Cultured endothelial cells from bovine thoracic aortas conditioned with serum free culture media released an endothelin-1 (ET)-1-like substance. Concentrations of ET-1-like material were determined by bioassay as contractions of isolated ring segments of dog internal mammary vein and by radioimmunoassay. ET-1-like immunoreactivity (ET-1-IR) increased progressively over a 24 h conditioning period and correlated with the bioassay for the first 12 h. Oxyhaemoglobin (1-3 microM) caused a significant two-fold increase in the concentration of ET-1-IR in the medium at 6, 8 and 12 h incubation. Methaemoglobin also caused an approximate doubling of the amount of ET-1-IR at eight h of incubation. NG-Monomethyl-L arginine (L-NMMA), a blocker of the production of endothelium-derived relaxing factor (EDRF), had no effect on the time-dependent increase in ET-1-IR in the conditioned medium. These results may have important implications for the mechanisms underlying vascular smooth muscle hyperreactivity such as cerebral spasm following subarachnoid haemorrhage. PMID- 1874285 TI - Inhibition of calcium entry induced by cularines and isocrasifoline in uterine smooth muscle. AB - The effects of nifedipine, papaverine and four benzylisoquinoline alkaloids (cularine, cularidine, celtisine and isocrasifoline) were studied in isolated rat uterus in order to clarify the mechanism of their relaxant action. All the compounds tested completely relaxed KCl-induced contractions and totally or partially inhibited oxytocin-induced rhythmic contractions. Only papaverine acted intracellularly, promoting relaxation of contractile responses induced by oxytocin or vanadate in a Ca(2+)-free medium. In spite of the structural relationship between papaverine and the other alkaloids, the mechanism of their relaxant action is not the same. The activities of cularine derivatives and of isocrasifoline were similar to that of nifedipine. PMID- 1874286 TI - Endothelial cells modulate the vasoinhibitory effect of NKY-722, a Ca2+ channel antagonist, in canine mesenteric arteries. AB - Modulation of the vasoinhibitory effect of NKY-722 by vascular endothelial cells was studied in canine mesenteric arteries. A high concentration of NKY-722 accumulated in the endothelium-intact arteries and its accumulation in endothelium-removed arteries was significantly less. The vasoinhibitory effect of NKY-722 in endothelium-intact arteries was significantly weaker than that in endothelium-removed arteries. These results suggest that endothelial cells can attenuate the vasoinhibitory effect of NKY-722. PMID- 1874287 TI - Free muscle transfer with split thickness skin graft coverage in head and neck reconstructive surgery. AB - Sixteen patients (eight females and eight males) who underwent microsurgical free tissue transfers for head and neck reconstruction are reviewed. In this series, the flap reconstruction was completed on eleven patients with extra-oral defects and five with intra-oral defects. Split thickness skin graft coverage was used in all cases. The rectus abdominis free muscle flap was used in nine patients and the latissimus dorsi free muscle flap in seven patients. The choice of tissue reconstruction was decided by the size of the surgical defect. There were no failures of the tissue transfers and skin grafts. In skilled hands, free tissue transfer provides a reliable method of head and neck reconstruction, with a low incidence of recipient and donor site complications. In extra-oral defects, coverage of free muscle transfer with split thickness skin grafts, results in a better colour match than musculocutaneous flaps, and complements the appearance and pliability of the free muscle flap. PMID- 1874288 TI - Squamous cell carcinoma of the oral tongue. AB - Between 1958 and 1983 at Beilinson Medical Center, Petah Tiqva, Israel, 75 patients were diagnosed as having squamous cell carcinoma of the body of the tongue. Of these, 42 were male and 33 female and the average age at the time of diagnosis was 61.6 years. 29.33% were in clinical stage I, 36% in stage II, 26.67% in stage III and 8% in stage IV. Fifteen patients underwent only surgery, nine received only irradiation and 51 received combined treatment. The 5-year survival rate was 68.3% with a significant difference between that for stage I (90%) and stage II (83.7%) and that for stages III and IV (43.07% and 0%, respectively) (P less than 0.001). Among the 24 with recurrence of the malignancy, 20 died despite treatment and four patients died of causes unrelated to the malignancy. From this experience it was concluded that local excision of the tumor should be performed only in stage I patients and that in stage II patients prophylactic treatment of the neck (neck dissection and irradiation) should be undertaken because of the high incidence of occult metastases. PMID- 1874289 TI - Nasopharyngeal carcinoma in Plateau State, Nigeria: a pathological study. AB - Nasopharyngeal carcinoma is rare in Central Nigeria where it represents 1.7% of all cancers. The prevalence rate is 4 per 100,000 and the male: female ratio is 2:1. Most tumours occur on the left side than the right (4:1) and the mean age at the time of presentation is 44.4 years. Undifferentiated and non-keratinizing carcinomas represent 60% of cases, while well differentiated squamous cell carcinoma accounts for 40%. PMID- 1874290 TI - Evaluation of resection margins after breast conservative surgery with monoclonal antibodies. AB - An immunocytochemical method for the detection of cancer cells, in the cell suspension obtained by scraping the surface of the surgical resection margins is described and its sensitivity compared to the conventional histology performed on random biopsies from the same margins. The reactivity of the cells with a pool of monoclonal antibodies (Mab) directed against epithelial markers indicated that in 80% of the 42 cases tested, the scraping method was adequate for the gathering of cells from the margins. The analysis of the samples using B72.3 Mab specific for tumor cells revealed that, among B72.3-positive tumor cases, 31% of breast margins contained tumor cells, whereas only 12% were histologically positive. Our results indicate that the immunocytological methodology is therefore more sensitive and should be used alongside histological examination to detect the tumor contamination in the surgical resection margins. PMID- 1874291 TI - Chest wall reconstruction after full thickness resection: an experience with 22 patients. AB - The authors present their experience of chest wall reconstruction after full thickness resection in 22 patients. The patients are from a series of 80 patients treated by chest wall resection from 1967 to 1989. Whether performed on breasts still in place, for recurrent disease, or for radiation-induced lesions (which are often associated), the defect created by complete resection of the chest wall layers causes difficulties. Large cutaneous flaps, often including the opposite breast were used at the beginning of the series. Then came omentum associated to Mersilene mesh and myocutaneous flaps. The results, in terms of comfort and local control are acceptable, even though surgery is only palliative for cancer patients. We feel that full thickness chest wall resection is the only effective treatment for some primary and recurrent malignant tumors and for extensive thoracic radionecroses. Such procedures are designed to improve the patient's quality of life even if they do not actually prolong survival. The goals guiding the reconstruction programme are: (1) the restoration of a stable parietal rigidity; and (2) the reconstruction of long lasting superficial layers. PMID- 1874292 TI - Nuclear morphometry of benign and malignant breast lesions. AB - The mean nuclear area (MNA) of mammary gland epithelium was measured in 403 breast specimens, comprising 239 invasive carcinomas, 49 carcinomas in situ, 45 cases of fibrocystic disease (f.c.d.) with intraductal epithelial hyperplasia, and 60 cases of f.c.d. without intraductal hyperplasia. Normal breast tissue adjacent to other benign or malignant lesions was measured in 170 specimens. Statistical analysis revealed no difference between the MNA of invasive ductal carcinoma and ductal carcinoma in situ. The MNA of lobular and ductal carcinomas were significantly different. Significant differences were also found between ductal carcinoma and the two classes of f.c.d. The MNA of f.c.d. with and without intraductal hyperplasia were also significantly different, the former having the highest MNA. All breast lesions showed MNA significantly higher than that of normal breast epithelium. These findings show that there is a gradual increase in MNA from the baseline value of normal breast epithelium, via fibrocystic disease without and with intraductal proliferation to invasive carcinomas. Measurement of MNA may aid in pinpointing cases of intraductal epithelial hyperplasia with malignant potential. PMID- 1874293 TI - Local tumor control by intra-operative radiotherapy (IORT): a pilot experience. AB - Patients with locally advanced disease, considered incurable by conventional therapeutic options, were treated, if possible, with surgical resection, and intra-operative radiotherapy (IORT) with or without external beam radiotherapy (EBRT), with the aim of improving local control of disease. Twelve patients were selected for IORT and eight patients were subsequently submitted to IORT in order to achieve local control. There were no IORT related complications, and local tumor control was achieved in all cases with a median follow-up of 22 months. IORT is a new and experimental treatment modality with a potential advantage over conventional radiotherapy. PMID- 1874294 TI - Use of the OM-11-906 monoclonal antibody for determining p62 c-myc expression by flow cytometry in relation to prognosis in colorectal cancer. AB - The expression of the c-myc protein product (p62 c-myc) and deoxyribonucleic acid (DNA) ploidy status was determined by a flow cytometric technique in 83 patients with colorectal cancer followed up for a median of 30 months (range 6-60 months). The OM-11-906 antibody, used to detect p62 c-myc, revealed a 62 kDa and 45 kDa band on Western blots in tumours. Correlation of quantitative dot blotting of tumour mRNA to flow cytometric p62 c-myc expression was good (r = 0.87, P less than 0.01). Levels of p62 c-myc varied in colorectal cancer and low levels (less than 20 fluorescein units) correlated with improved survival (log rank chi 2 = 4.69, df = 1, P = 0.03), and this was a better prognostic index than DNA ploidy (log rank analysis chi 2 = 2.38, df = 1, P less than 0.1). Although expression of the c-myc gene was found, using the OM-11-906 antibody, to be a prognostic feature in colorectal cancer, these and other results need to be interpreted with caution given the presence of two protein bands by Western blotting. PMID- 1874295 TI - Local and systemic effects of repeated intraperitoneal epirubicin treatment. AB - The local toxicity, general morbidity and mortality of repeated intraperitoneal administration of epirubicin (0.5 mg/kg in 100 ml isotonic saline) was investigated using a rat model. This dose is equivalent to that which would be used in the human. After six perfusions, the incidence of peritoneal inflammation was similar in the epirubicin group and saline controls. The vesicant properties of the drug were reflected in a significantly higher incidence of peritoneal fibrosis (P = 0.0015) but adhesions were more common in the controls (29%) than in the epirubicin perfused animals (4%). Animals from both groups showed inflammatory collections within the liver. There were no chronic hepatic lesions such as fibrosis/cirrhosis. This may be owing to portal bacteraemia caused by repeated cannulation of the peritoneal cavity. Evidence of microabscess formation in the hepatic parenchyma was observed in both animals. No histologically demonstrable toxicity was observed in the heart or gastrointestinal tract of the animals included in this study. The mortality of the epirubicin treated rats (2/146 perfusions) was similar to that of the saline controls (2/84 perfusions). These findings indicate that repeated intraperitoneal perfusion with epirubicin is not associated with significant toxicity. This anthracycline is therefore suitable for prolonged cyclical intraperitoneal chemotherapy. PMID- 1874296 TI - Choroid metastasis from nasopharyngeal carcinoma. AB - A case of choroid metastasis from nasopharyngeal carcinoma (NPC) is presented. If loss of vision in patients with NPC is not associated with proptosis or weakness of the extra-ocular eye muscles after radiotherapy, investigations to exclude choroid metastasis should be carried out. Choroid metastasis, in contrast to the more common causes of loss of vision in such a situation, radiation retinopathy and optic neuropathy, is amenable to treatment to prevent irreversible blindness and enucleation for intractable glaucoma pain. PMID- 1874297 TI - Malignant granular cell tumour of the oesophagus. PMID- 1874298 TI - Bilateral adrenal lymphoma presenting as Addison's disease and hypercalcaemia. AB - The adrenal gland is not uncommonly involved in lymphoma. It is rare, however, for adrenal lymphoma to present as Addison's disease. There are only eight reports in the English literature. This paper reports a case of adrenal lymphoma that presented with Addison's disease and hypercalcaemia. PMID- 1874299 TI - Squamous carcinoma of the colon: primary or metastatic? AB - A patient is reported who developed a tumour of the transverse colon, which at presentation appeared histologically and clinically to be a primary squamous cell keratinizing carcinoma, arising from an area of in situ carcinoma in the colonic epithelium. However, she had had a stage 1 cervical carcinoma treated by Wertheim's hysterectomy 7 years previously and although there were no other signs of recurrence, this raised the possibility that the lesion might be metastatic. Thirty-seven previously reported cases of primary squamous carcinoma of the colon and those of squamous carcinoma metastasizing to the colon and mimicking primary lesions are reviewed. PMID- 1874300 TI - Second hepatic resection for metastatic colorectal cancer. AB - We report a case where repeat hepatic resection was successfully performed 3 years after extended right hepatic lobectomy for metastatic colorectal cancer. The patient remains well and disease free 2.5 years after the second hepatic resection. PMID- 1874301 TI - Placental alkaline phosphatase in seminoma. PMID- 1874302 TI - [The hypomenstrual syndrome and amenorrhea in adolescent girls]. PMID- 1874303 TI - [Uterine myoma]. PMID- 1874304 TI - [Hemophilia]. PMID- 1874305 TI - [Blepharitis]. PMID- 1874306 TI - [The clinical picture and treatment of tuberculous spondylitis]. PMID- 1874307 TI - [Syringomyelia]. PMID- 1874308 TI - [Gout]. PMID- 1874309 TI - [The late treatment results in congenital hip dislocation in childhood]. PMID- 1874310 TI - [Emergency care for the victims in mass disasters in peacetime]. PMID- 1874311 TI - [The principles of the organization and rendering of resuscitation care in road traffic accidents]. PMID- 1874312 TI - [Transportation immobilization in injuries to the locomotor apparatus]. PMID- 1874313 TI - [Suppurative bacterial meningitis of pneumococcal and Haemophilus etiologies]. PMID- 1874314 TI - [A method for examining the therapeutic patient]. PMID- 1874315 TI - [Corpulence and fertility]. PMID- 1874316 TI - [Secondary amenorrhea in adolescents on a cosmetic diet]. PMID- 1874317 TI - [Developmental defects of the genitalia in girls]. PMID- 1874318 TI - [Constipation in young children]. PMID- 1874319 TI - [Liver cirrhosis]. PMID- 1874320 TI - [Systemic lupus erythematosus]. PMID- 1874321 TI - [The use of therapeutic plasmapheresis in dermatological practice]. PMID- 1874322 TI - [Dupuytren's disease]. PMID- 1874323 TI - [Medical first aid in chest trauma]. PMID- 1874324 TI - [Interferon and its inducers in the therapy of recurrent herpes]. PMID- 1874325 TI - [The organization of gynecological care for girls and young women]. PMID- 1874326 TI - [The characteristics of Bela's wound--the heroine of the story of the same name by M. Iu. Lermontov]. PMID- 1874327 TI - [Orderly No. 9999 (episodes out of the life of Sergei Esenin)]. PMID- 1874328 TI - Organ donation: it begins with you! PMID- 1874329 TI - Flexible scheduling and part-time work. PMID- 1874330 TI - Competence statements for differentiated nursing practice in critical care. AB - The demand for high-quality patient care in the current complex health care environment and the variety of today's available nursing education programs dictate a need to differentiate nursing practice into technical and professional roles. These roles are based on competencies acquired in ADN and BSN degree programs and implemented in practice settings where the contributions of all nurses are valued. To create a preferred future, AACN has developed a model for differentiated nursing practice in critical care. The model is a guideline for those nurses and institutions who may be or will be involved in changing practice patterns. The model does not support or encourage the elimination or disenfranchisement of any individual or groups of nurses. These statements were developed to address specific behavior that reflects the valuable contributions of each category of nurses within critical care nursing. The statements provide a model for creating efficient and effective practice patterns that may contribute to high-quality outcomes for critically ill patients and their families. PMID- 1874331 TI - Silent myocardial ischemia. PMID- 1874332 TI - The legal basis of expert testimony. PMID- 1874333 TI - Removal of pulmonary artery catheters by registered nurses: a study in safety and complications. PMID- 1874334 TI - Torture and abuse of our health care colleagues. PMID- 1874335 TI - Implications of clinical reasoning studies for critical care nursing. PMID- 1874336 TI - Critical care nurse model. AB - An innovative organizational framework is proposed in which professional group practices provide health care services by contract to hospitals and nurses and other health care providers have equal authority and power. Using this model, nurses can form group practices and contract with hospitals to provide total critical care nursing services to patients in hospital units. PMID- 1874337 TI - Critical care nurses' interactions with families of potential organ donors. PMID- 1874338 TI - Radioprotective effect of dextran sulphate and aerogenic hypoxia on intestinal crypt stem cells in mice. AB - A single intraperitoneal injection of dextran sulphate given 6 h before irradiation produced higher numbers of microcolonies of intestinal crypt stem cells in whole-body irradiated mice than injection of saline in control mice. If dextran sulphate and hypoxia are combined, the radioprotective effect of hypoxia on intestinal crypt stem cells depends on the time interval between irradiation and administration of dextran sulphate. PMID- 1874339 TI - Thyroid hormone analogue SKF L-94901 accelerates regression of Moloney sarcoma and inhibits periosteal osteogenesis mediated by this tumour. PMID- 1874340 TI - Further possibilities of using aryloxycarbonic acid derivatives in clinical practice. AB - In medical practice aryloxycarbonic acid derivatives have been solely used in the treatment of hyperlipidemia. Recently we patented the use of some of these derivatives in the treatment of dermatological diseases. Further analyses showed that these substances stimulated various cells of mesodermal origin including lymphocytes, the principal cells of the immune system. Depending on the concentration some derivatives of aryloxycarbonic acid stimulated or suppressed the proliferative response of lymphocytes, pointing to the possible use of these drugs as immunomodulators in clinical practice as well. PMID- 1874341 TI - A natural specific intracellular ligand as a reagent for cyclosporine blood level determination. AB - We isolated and characterized a non-immunoglobulin fraction from calf thymuses which was found very active in binding [3H]labelled cyclosporine (CsA). It contains the natural, intracellular receptor cyclophilin, specifically binding to the active site of the CsA molecule, which may also play a part in the immunosuppression of human immunocompetent cells. This material with a high selectivity could be used, instead of specific monoclonal or polyclonal antibodies, to determine CsA levels in patient's blood. PMID- 1874342 TI - In vitro and in vivo organ cultures containing respiratory epithelium. AB - A combination of two methods, organ culture and transplantation under the kidney capsule of nude mice, can be a suitable tool to study the mechanism of carcinogenesis of the human respiratory epithelium and to detect risks in environmental pollution. We used two tissues containing the respiratory epithelium--rat lung and human vocal cord. Gelita, a porous material used in surgery for haemostasis, produces a good support for the growing organ cultures of both tissues. These tissues continue to grow and to differentiate after transplantation under the kidney capsule. No pronounced immunological reaction of the nude mouse was detected. These conditions not only allow us to test various carcinogenic substances and their combinations, but as well enable us to detect an eventual malignant growth. PMID- 1874343 TI - Pregnancies after transfer of sheep embryos produced from oocytes matured and fertilized in vitro. AB - The experiments describe simple and effective methods used for the production of sheep embryos in vitro. The oocytes isolated from the ovarian follicles, 2-5 mm in diameter, were matured in culture for 22-24 h. After mixing with ram spermatozoa pretreated with heparin, 77-100% of fertilized oocytes were monospermic. Some of them (60-68.3%) cleaved in culture after 24-50 h to 2-4-cell stage. The transfer of cleaved embryos to the oviducts of 4 synchronized recipients resulted in pregnancies and 4 normal lambs were born at term. PMID- 1874344 TI - Legionnaires' disease. PMID- 1874345 TI - Sports injuries and adolescent athletes. AB - A one-year study was undertaken investigating adolescent sports injury experiences at a major sports clinic in the state of Delaware. A total of 619 athletes sustained 870 injuries, for an overall injury rate of 1.4 injuries per athlete. The largest number of injuries was recorded in football (40.2 percent), followed by boys' soccer, wrestling, baseball and girls' basketball. Severity of injury was measured by the number of days lost per injury. Cheerleading had the highest average days lost per injury (28.8), followed by girls' basketball, wrestling, boys' cross-country and girls' tennis. Inflammation, fractures and dislocations comprised 50.6 percent of all the injuries, while 50.5 percent of the injuries were located in the knee, thigh, and shoulder. Twenty-seven of the 870 injuries required surgery. PMID- 1874346 TI - Cat scratch encephalopathy. AB - Cat scratch disease is usually benign, self-limited and without sequelae. Margileth has established four clinical criteria, three of which must be satisfied to make the diagnosis: 1) a history of animal exposure, usually kitten, with primary skin or ocular lesions; 2) regional chronic adenopathy without other apparent cause; 3) a positive cat scratch disease antigen skin test; and 4) lymph node biopsy demonstrating noncaseating granulomas and germinal center hyperplasia. Central nervous system involvement in cat scratch disease has been previously reported, although it is extremely uncommon. In a several-month period, we encountered two cases of cat scratch disease complicated by encephalopathy. The intents of this paper are twofold: 1) to briefly review the current literature on cat scratch disease, 2) to demonstrate that cat scratch disease complicated by encephalopathy presents acutely with seizures, posturing and coma and resolves rapidly with supportive care. PMID- 1874347 TI - HIV-infected physicians. PMID- 1874348 TI - Disputing reports made to the National Practitioner Databank. PMID- 1874349 TI - The Herbst appliance. PMID- 1874350 TI - Sectional dentures: the manufacture of bolt and bolt hole. PMID- 1874351 TI - Maxillo facial injuries and maxillofacial laboratory services: a five-year review. PMID- 1874352 TI - 27th annual meeting of the European Association for the Study of Diabetes. Dublin, Ireland, 10-14 September 1991. Abstracts. PMID- 1874353 TI - The heartsink patient: a preliminary study. AB - Eight GPs identified 78 heartsink patients; in an open-ended interview they were asked to explain why they regarded them in this way. A GP's definition of a heartsink patient was influenced by GP sex, practice location, and time of surgery, although the number of participating GPs was too low to make any definite assertions. Practitioners' anticipations of heartsink consultations were generally over-exaggerated, with most of the encounters going better than expected. GPs expressed the view that these patients raised serious professional issues for them, whilst there was also a dislike for these patients' personalities and behaviour. Two levels of the heartsink state are hypothesized: one, a state of inertia, is when the heartsink patient has been a chronic high user of the primary health care system, and a GP has exhausted all avenues. The other is an acute situation with those heartsink patients who have been low users of the system in the past. Recent, new events in these patients' lives have raised an issue that is just as much to do with patient and doctor reaction to these events, as it is about finding a diagnosis or solution to the problem. We present the results and hypotheses to provoke further discussion and research. PMID- 1874354 TI - Managing miscarriage: the management of the emotional sequelae of miscarriage in training practices in the West of Scotland. AB - Miscarriage is a very common event which is rarely a medical emergency, and which, from a biomedical perspective, may justifiably be viewed as a 'normal' complication of early pregnancy. From the mother's point of view however, the loss of a wanted pregnancy may be viewed quite differently. A number of studies have identified significant levels of dissatisfaction with the medical care which women have received at the time of a miscarriage. This paper describes a survey of the management of miscarriage by general practitioner trainees and trainers in the West of Scotland and on the basis of responses to a series of MEQ-type questions, indicates GPs views on the importance of counselling, sympathetic listening and good information in this area. The translation of these attitudes and beliefs into practice is, of course, a different issue, and one which may be affected by the task-oriented approach of the new contract. PMID- 1874355 TI - Chest pain: an evaluation of the initial diagnosis made by 25 Flemish general practitioners. AB - Twenty-five general practitioners collected information on 318 contacts of patients with a new episode of chest pain, discomfort or tightness. A list of complaints, signs and symptoms were checked, together with the initial diagnosis, made by the GP immediately after the physical examination. The initial diagnosis was compared to a follow-up diagnosis. The gain in certainty was also compared. The GP made a correct initial diagnosis in 82% of patients. In 8% there was a clinically important difference, and seven of 17 episodes of oesophageal disease were missed. For their initial diagnosis, the GP scored 74% certain, 20% uncertain and no diagnosis in 6%. For the final diagnosis, these figures were 88%, 8% and 4%. PMID- 1874356 TI - Dutch general practice care for patients with epilepsy: results from the Dutch National Survey of Morbidity and Interventions. AB - This study aimed to assess the share which Dutch general practice has in the care of patients with epilepsy. During a 3-month period 400,000 patient contacts in 103 general practices with a total list of 335,000 patients were registered, 1536 of these, concerning 1059 patients, concerned epilepsy. Contacts with patients with known epilepsy in Dutch General Practice were handled mainly by the practice nurse and most involved repeat prescriptions. Patients suspected of having epilepsy had more attention from the General Practitioner. The involvement of General Practitioners in the care of epilepsy was found to be small, but not unimportant. GPs are in a crucial position as regards the detection of epilepsy. They can enlarge their role in respect of patients with known epilepsy and improve continuity of care. PMID- 1874357 TI - Patients' views on health screening in general practice. AB - This paper describes the reactions of 159 patients to the way in which they were invited to participate in a health screening programme and their views on the screening appointment itself. It was found that those invited by letter, rather than opportunistically during a routine consultation, thought their appointment time harder to keep. A group of patients identified as relatively infrequent consulters were less likely to believe that the invite showed the practice to be interested in their health. However, overall the patients' perceptions of both the way in which they were invited and the screening appointment itself were found to be very positive and their satisfaction ratings high. PMID- 1874358 TI - Patient education in family practice: the consensus reached by patients, doctors and experts. AB - Patient education is a central aspect of the GP's work, but it is not clear what type of information and guidance should be given to patients during consultations. As the existing literature did not offer any clear solutions to this problem, a consensus study was carried out using a panel of GPs, patients and experts/policymakers in the field of health education. After three cycles of questioning involving written questionnaires and written feedback, the panel reached a consensus on 35 priorities and recommendations concerning patient education carried out by the GP. A consensus method of this type is a valuable tool for setting standards when scientific findings are not available, and contrasting views play a role in the definition of what constitutes adequate performance. PMID- 1874359 TI - Job stress in general practice: practitioner age, sex and attitudes as predictors. AB - South Australian general practitioners (n = 966) provided information in a questionnaire study about four indicators of job stress: the burnout components of emotional exhaustion, depersonalization, and personal accomplishment, and a three-item measure of job dissatisfaction. As job stress can arise from discrepancies between the nature of the work and the expectations of the worker, attitudes to general practice form and content were surveyed, using an existing Australian scale. This study largely replicated the factor structure originally reported for the scale. Up to one third of respondents reported significant levels of job stress, which varied according to age and sex as well as attitudes to general practice. PMID- 1874360 TI - Violence to general practitioners and fear of violence. AB - This paper describes the perception of general practitioners of violence to which they are subject, and also their fears of violence. It is based on interviews, and a written questionnaire. The outcome suggests that violence is a formidable problem. Some coping strategies are described. On the whole the subject has been little ventilated, but its recognition is an urgent matter. PMID- 1874361 TI - Fever: management and self-medication. Results from a Norwegian population study. AB - A representative sample of the Norwegian population was interviewed in 1988 as part of a monthly national opinion poll to investigate lay management and self medication of fever. Six hundred and nineteen women and 592 men over the age of 15 were interviewed in their homes. Approximately one-fifth reported inappropriate measuring of body temperature. A variety of management and self medication was found. In cases of common cold or influenza with fever, 35% would use antipyretics. Forty per cent would start to use antipyretics at a temperature below 39.0 degrees C. Forty-four per cent did not know any antipyretic brand names at all. The results indicate a need for more definite and consistent information to make fever management and self-medication more rational. Such information should be discussed and given by general practitioners, nurses at child welfare centers and pharmacists. PMID- 1874362 TI - Connections between the quality of consultations and patient compliance in general practice. AB - The aim of the study was to generate and test a theory about connections between the quality of consultations and patient compliance in general practice. The theory was empirically based on patient interviews in order to understand the patient's perceptions and behaviour, and on development of a list for mapping of consultations, which in turn allowed coherent descriptions of consultations and compliance. The theory suggests and explains that compliance is connected with the fulfillment of six relatively simple criteria for the quality of consultations. The theory was tested by comparing predictions of compliance derived from analyses of 63 consultations with patient questionnaire based measurements of compliance. The difference between proportions of patients who were complaint after consultations fulfilling and not fulfilling respectively the criteria was 44%. The 95% confidence limits of this difference were 21% and 67%. PMID- 1874363 TI - Primary care research in Latin America, Portugal and Spain. PMID- 1874364 TI - Acupuncture: from needle to laser. AB - Acupuncture has been used in the treatment of a variety of illnesses for more than 2000 years. The practice of acupuncture is based on a theoretical system different from our understanding of human anatomy and physiology, and has developed through experience and observation. Stimulation of selective acupoints (situated along 'meridians' in the body) by inserting needles is believed to restore bodily functions by promoting the flow of 'vital energy', throughout the system. Other forms of stimulation which have been developed are heat, electrical stimulation, magnetism and, recently, laser. Laser acupuncture offers distinct advantages over the traditional method because the procedure is pain-free and non traumatic. Clinical applications include the control of pain in osteoarthritis, lumbago and migraine, and anaesthesia for certain surgical procedures, as well as other ailments of the cardiovascular, respiratory and nervous systems. The technique is easy to learn and there is no need for sophisticated instruments. Thus it is especially useful in developing countries where health resources are limited. PMID- 1874365 TI - The reliability and criterion validity of a measure of patients' satisfaction with their general practice. AB - The Surgery Satisfaction Questionnaire (SSQ) was developed using the methods of psychological test construction, and designed to determine patients' satisfaction with the services offered to them by their general practitioners. Principal components analysis (PCA) revealed five components distinct from general satisfaction--continuity, accessibility, availability, medical care and premises. Reliability as determined by a split-half test (coefficient alpha) was adequate but should be improved in future versions of the questionnaire. A study of criterion validity was undertaken to test the questionnaire and to develop methods of testing the validity of measures of patient satisfaction. The two criteria used were the doctors' self-assessment of their own practices and the assessment of an external assessor. The findings supported the validity of the components of continuity, accessibility, availability and premises, but the patients' scores correlated better with the external assessors' scores than the doctors' self-assessed scores. SSQ is a useful foundation for the development of measures of patient satisfaction in general practice. PMID- 1874366 TI - [Features of the thrombocytic component of hemostasis in newborns and mechanisms of its disorders]. PMID- 1874367 TI - [Thrombocytopenic states in the neonatal period]. AB - A total of 316 cases of thrombocytopenic states were analyzed in newborns. The incidence rate of thrombocytopenia among mature infants with varying diseases comprised 37%, hemorrhagic syndrome developed in 23.7% of them. Among the infants admitted to hospital with hemorrhagic syndrome thrombocytopenia was detected almost in half the cases (42%). Most often thrombocytopenia was observed in infections diseases, both intrauterine and postnatal. Transplacental and isoimmune thrombocytopenic purpura comprised 6.3% of all cases, thrombocytopenia caused by amegakaryocytosis--1.5%. Basing on the analysis made three variants of transplacental thrombocytopenic purpura have been distinguished and described. Causes and pathogenesis of thrombocytopenia development in infectious diseases of newborns are discussed. PMID- 1874368 TI - [Microrheologic properties of erythrocytes and parameters of vascular thrombocytic hemostasis in newborns with perinatal pathology]. AB - Hematocrit, thromboelastogram, aggregation capacity of platelets and red blood cells, the content of prostaglandin metabolites--prostacyclin 6-keto-PGF and thromboxane B (TxB) were studied in 70 newborns who had suffered perinatal hypoxia and localized pyo-inflammatory diseases that developed during the first week of life. It has been found that the pronounced disturbances of the peripheral blood circulation and frequent hemorrhagic complications in the infants with these diseases are closely connected with disorders in the aggregation capacity of red blood cells and platelet function due to the imbalance of the prostacyclin-thromboxane-generating system. PMID- 1874369 TI - [Embryonal and fetal hematopoiesis: current problems]. PMID- 1874370 TI - [Immunosuppressive factors of placental blood serum]. AB - The action of soluble factors responsible for the immuno-suppressive effect of placental blood serum and placental extracts has been analyzed. It has been shown that fetoplacental proteins, trophoblastic antigens, antibodies to histocompatibility antigens, receptors to Fc-fragments of IgG participate in the realization of immunosuppression during pregnancy. Data have been presented on the possibility of using immunosuppressive properties of placental blood for production of a gamma-globulin immunomodulating preparation. PMID- 1874371 TI - [Intravascular hemolysis in hemolytic disease of newborns]. PMID- 1874372 TI - [Rheologic and immunologic blood parameters in patients with hypoplastic anemia who received antilymphocytic globulin]. AB - Basing on the results of the investigation of patients with hypoplastic anemia attended by rheological and immunological disorders who received antilymphocytic globulin, the authors have recommended that the combined therapy of these patients should include lymphocytoplasmapheresis promoting removal of antibodies damaging lymphocytes, their decomposition products, circulating immune complexes, as well as heparin and antiaggregants that allow one to escape the side effects of antilymphocytic globulin. PMID- 1874373 TI - [Scientific and practical problems of neonatal hematology]. PMID- 1874374 TI - [Myelopid correction of disorders in marker characteristics of surface membrane and cytoplasm of neutrophil granulocytes in children with pyoseptic diseases]. PMID- 1874375 TI - [Immunodiagnosis of HIV infection in the transfusion service]. AB - Enzyme immunoassay (EIA) is the basic method of the laboratory diagnosis of HIV infection used as the first component of donors' screening. The possibility of nonspecific reactions presents a significant shortcoming of this method. An algorithm involving three stages has been elaborated to investigate donors for anti-HIV antibodies and to verify seropositive samples. The first-stage screening is conducted with the use of Soviet test-reagents. Positive samples are assayed again in the Soviet EI-systems based on varying types of sorbed antigens. In case of questionable or positive reactions the sample is assayed in commercial imported test-systems (the second stage). The positive sera are assayed in the immunoblotting test (the third stage). The algorithm suggested provides a reliable control and is worthwhile economically. The causes of nonspecific reactions in EIA have been described. PMID- 1874376 TI - [Hemoblastosis epidemiology in the Chernobyl region. I. Organization of research in the Homel'sk Region]. PMID- 1874377 TI - [Arterial thrombosis in a patient with protein C deficiency]. PMID- 1874378 TI - [Role and physiologic importance of thrombinemia in healthy newborns]. AB - The sensitive orthophenanthroline test was used to reveal paracoagulation in 27 normal newborns, thrombinemia reaching the highest level at the moment of birth and in the period of heavy depression of blood coagulation (on the fifth day of life) was detected. It has been suggested that the physiological role of thrombinemia is in the leveling of hypocoagulation shifts and providing of the local hemostasis. To escape thrombotic complications, drug correction of the hypocoagulation physiological level (activity of prothrombin complex factors is 30-60%) is not recommended. PMID- 1874379 TI - [Ontogenetic features of hemostasis and urine fibrinolysis in newborns]. AB - Parameters of hemostasis and urine fibrinolysis were studied in the ontogenesis of 56 normal newborns aged from 3 to 28 days. The data obtained and the correlation analysis made have shown significant changes in the hemostasis system in the ontogenesis. The neonatal period is characterized by stage changes in the hemostasis system that reflect the processes of adaptation for intrauterine existence, hypocoagulation being changed by mild hypercoagulation followed by coagulation formation by the end of the first month of life. Maximum statistically significant correlations were revealed during the first week of newborns' life. The data obtained can be used as control during the study of varying pathological states associated with changes in the coagulation and anticoagulation systems in newborns. PMID- 1874380 TI - Effects of serotonin on gonadotropin and growth hormone release from in vitro perifused goldfish pituitary fragments. AB - The effects of serotonin (5-HT) on gonadotropin and growth hormone release from perifused goldfish (Carassius auratus, L.) pituitary glands were studied. Serotonin, at micromolar concentrations, caused a dose-related release of gonadotropin and an inhibition of growth hormone release in pituitaries from goldfish at different sexual stages. At lower concentrations 5-HT continued to inhibit growth hormone release, but had no effects on gonadotropin release. The stimulatory effects of 5-HT on gonadotropin release could be blocked by ketanserin and cyproheptadine; however, these two antagonists had no effects on 5 HT inhibition of growth hormone release. Perifusion with melatonin had no effect on the release of gonadotropin or growth hormone release. These results demonstrate that 5-HT has a stimulatory effect on gonadotropin secretion, probably through a 5-HT2 receptor type, and an inhibitory effect on growth hormone through an unidentified receptor type. We hypothesize that the effects on gonadotropin release are due to direct actions on gonadotrophs, whereas the effects on growth hormone release may be due to stimulation of somatostatin release from neurosecretory terminals in the pituitary. PMID- 1874381 TI - Plasma estradiol-17 beta, progesterone, prostaglandin F, and prostaglandin E2 concentrations during natural oviposition in the loggerhead turtle (Caretta caretta). AB - Changes in plasma concentrations of steroids and prostaglandins (PGs) during natural nesting and oviposition in the loggerhead turtle were studied. Blood samples were obtained during nine distinct behavioral stages of oviposition. Emerging females had no detectable prostaglandin F (PGF) or prostaglandin E2 (PGE2) whereas plasma estradiol-17 beta averaged 255 pg/ml and mean plasma progesterone was 395 pg/ml. Plasma steroid concentrations did not vary significantly during nesting. In contrast, plasma PGF and PGE2 exhibited significant elevations during nest digging about 15 min after emergence. A further significant increase in plasma PGs was observed 10 min later during early oviposition. Plasma PGE2 peaked during mid oviposition whereas maximal plasma PGF levels occurred during nest covering although mean values were not significantly different than those observed during oviposition. Both PGs showed an abrupt decline (within 10 min) during body pit covering to concentrations similar to those observed during nest construction. Our data suggest that PGs have an active role during oviposition and nesting in the loggerhead turtle and are consistent with hypotheses that PGF2 alpha stimulates uterine contractions promoting egg expulsion while PGE2 may be more important in promoting cervical relaxation. PMID- 1874382 TI - Interaction of salmon glucagon, glucagon-like peptide, and epinephrine in the stimulation of phosphorylase a activity in fish isolated hepatocytes. AB - The simultaneous addition of epinephrine and salmon glucagon to catfish (Ictalurus melas) and trout (Salmo gairdneri) hepatocytes did not induce greater increases in glycogen phosphorylase a activity and in glucose release than those caused by epinephrine alone. The effects of epinephrine are greater than those of glucagon. Propranolol added to the hormonal pool blocked the epinephrine effects. In trout cells, epinephrine and glucagon-like peptide (GLP) had similar effects and when they were added simultaneously the stimulation of metabolic indices was higher compared to that obtained with either epinephrine or GLP. However, the effects were not additive. In the presence of epinephrine plus GLP the inhibitory effect of propranolol was not evident, due to the effect induced by GLP, on which propranolol was not effective. This may indicate that epinephrine masks the GLP effect. Results could mean that epinephrine and glucagon-family peptides act in catfish and trout hepatocytes through different receptors on the same pathway leading to glycogen phosphorylase a activation. PMID- 1874383 TI - Homologous radioimmunoassay for bullfrog growth hormone. AB - Antiserum against bullfrog growth hormone (fGH) was produced by immunizing rabbits with the highly purified fGH obtained from adenohypophyses of adult bullfrogs. Histological studies on bullfrog adenohypophyses revealed that the cells that immunologically reacted with the antiserum against fGH corresponded to the ones positively stained with the antiserum against rat GH. The antiserum together with fGH and 125I-fGH was employed to develop a radioimmunoassay (RIA) for fGH. Several dilutions of plasma and of pituitary homogenate of both adult and larval bullfrogs yielded dose-response curves which were parallel to the standard curve. Ovine prolactin (PRL), and growth hormone (GH); eel and salmon GHs; and bullfrog LH, FSH, TSH, PRL, and neurointermediate lobe homogenate did not react in this assay. Plasma from hypophysectomized bullfrogs had no detectable immunoreactive GH. Pituitary homogenates of Bufo japonicus, Xenopus laevis, and Cynops pyrrhogaster gave inhibition curves which did not parallel the standard. The homologous RIA for bullfrog GH thus developed was applied for the determination of plasma and pituitary GH levels in the larvae and adults. Plasma GH levels were relatively low during preclimax period and rose as metamorphosis progressed. Plasma GH concentrations were maximum in the juvenile frogs and decreased as the animals grew up. Pituitary GH concentrations also increased as metamorphosis progressed. After metamorphosis, pituitary GH concentrations declined as the frogs gained weight. There was no sex difference in plasma and pituitary GH levels in the adult. PMID- 1874384 TI - Plasma arginine vasotocin, progesterone, and luteal development during pregnancy in the viviparous lizard Tiliqua rugosa. AB - The relationship between plasma levels of arginine vasotocin (AVT), progesterone, and corpus luteum formation and degeneration was studied in the viviparous lizard Tiliqua rugosa. Hormone levels were monitored in free-ranging, pregnant females which were located for sampling by means of attached radio transmitters. There was an increase in plasma AVT levels in the 30 days immediately prior to parturition. Concurrent with this event was a decline in plasma progesterone levels from relatively high levels in mid-term to basal levels prior to parturition. This is associated with degenerative changes in the corpus luteum which include pyknosis of the nuclei of the cells of the cell mass and increasing prevalence of intercellular spaces, while the thecal layer became increasingly compacted. Ovariectomy experiments indicate that the major source of progesterone during pregnancy in T. rugosa is ovarian. PMID- 1874385 TI - The primary structure of glucagon-like peptide but not insulin has been conserved between the American eel, Anguilla rostrata and the European eel, Anguilla anguilla. AB - Insulin was isolated from the pancreas of the American eel, Anguilla rostrata, and its primary structure was established as (Formula: see text). Eel insulin contains unusual substitutions at B-21, B-22, and B-26 in the putative receptor binding region of the molecule compared with other mammalian and fish insulins. The A-chain of insulin from the European eel contains an asparagine rather than a serine residue at position A-12. Similarly, amino acid composition data indicate the B-chain of insulin from the European eel is appreciably different from that from the American eel. The primary structure of glucagon-like peptide (GLP) from the American eel is identical to that from the European eel, Anguilla anguilla. The primary structure of the peptide was established as (Formula: see text). Fast atom bombardment mass spectrometry demonstrated that the COOH-terminal arginyl residue is alpha-amidated. The strong evolutionary pressure to conserve the structure of GLP provides further support for the assertion that the peptide plays an important regulatory role in teleost fish. PMID- 1874386 TI - Seasonal changes in seawater adaptability and plasma levels of prolactin and growth hormone in landlocked sockeye salmon (Oncorhynchus nerka) and amago salmon (O. rhodurus). AB - In order to clarify the roles of prolactin (PRL) and growth hormone (GH) in the development of seawater adaptability in salmonids, seasonal changes in salinity tolerance, plasma PRL, and plasma GH were examined in juvenile landlocked sockeye salmon (Oncorhynchus nerka) and amago salmon (O. rhodurus). Assessed by the 24-hr seawater-challenge test, the landlocked sockeye salmon possessed seawater adaptability as underyearlings in spring, which was maintained throughout the year, and a further increase was observed as yearlings the next spring. An increase in seawater adaptability was observed in silvery juvenile amago salmon as underyearlings from autumn to winter, when some of the wild population migrate to the sea. Precociously mature amago salmon, which did not develop a silvery body color but maintained distinct parr marks, also showed an improvement in seawater adaptability during autumn to winter, although plasma sodium levels after transfer to seawater were still higher than those of the silvery juveniles. In both sockeye and amago salmon, seasonal changes in plasma levels of PRL and GH were not correlated with development of seawater adaptability. In both species, acclimation to seawater resulted in decreased plasma levels of PRL irrespective of their adaptability to seawater, in agreement with the inhibitory effects of PRL in seawater adaptation. On the other hand, plasma GH levels increased only when seawater adaptability was high, in agreement with previous observations indicating an important role of GH in seawater adaptation of salmonids. PMID- 1874387 TI - Neuroendocrine factors affecting the glycogen metabolism of purified Mytilus edulis glycogen cells: partial characterization of the putative glycogen mobilization hormone--demonstration of a factor that stimulates glycogen synthesis. AB - A putative glycogen mobilizing hormone (GMH) from the marine mussel Mytilus edulis L. has been partially characterized. GMH activity is present in the cerebral ganglia and the hemolymph serum and promotes the mobilization of glycogen in isolated glycogen cells. The cerebral GMH is trypsin sensitive and partially heat labile and has an apparent molecular mass of greater than 20 kDa. Following fractionation of cerebral extracts by molecular mass, a second factor, with a molecular mass of ca. 1.5 kDa, was discovered. This factor stimulates post incubation incorporation of 14C into glycogen in isolated glycogen cells. PMID- 1874388 TI - Assay validation and characterization of hepatic 5'-deiodinase activity in ring doves using reverse-T3 as substrate. AB - Adult ring dove hepatic 5'-deiodinase (5'D) activity was studied in vitro using reverse T3 (rT3) as substrate. A previous study of ring dove hepatic deiodinase in our laboratory did not include characterization studies and was unsuccessful in relating the pattern of 5'D development to that of plasma T3. In the present study we established valid assay conditions and characterized the hepatic 5'D in doves to provide a comparison with other avian species and 5'D activity is proportional to enzyme concentration (as postmitochondrial fraction (PMF) protein) over the range measured (0-0.163 mg PMF protein/ml, representing 0-2.19 mg original tissue/ml). Activity was linear with time from 5 to 30 min of incubation at 0.163 mg PMF protein/ml. Our 5'D assays used 20 mM DTT; activity was maximal from 5 to 30 mM DTT. Using the validated conditions the following characteristics were found: the apparent Km was 0.44 microM rT3, Vmax was 255 pM rT3 degraded/min-mg PMF protein, and activity was completely inhibited by 1 mM PTU. Activity was maximal at pH 8.04 and at 37.5 degrees (although this did not differ from activity at 41.5 degrees, the body temperature of doves). In summary, this study demonstrates conditions that measure 5'D at initial velocities in dove liver and demonstrates that the hepatic 5'D enzyme in ring doves is similar to the deiodinase activity in liver of galliform birds and mammals. PMID- 1874389 TI - Demonstration of putative thyroid hormone receptor in the brain nuclei of Singi fish, Heteropneustes fossilis (Bloch). AB - A single injection of [125I]triiodothyronine (T3) with or without stable T3 in Singi fish, Heteropneustes fossilis (Bloch), showed that the fish brain has saturable binding sites and that the specific uptake is 60-70% higher than the nonspecific uptake. The distribution kinetics of [125I]T3 in the serum, whole brain, and brain nuclei after a single injection of the labeled hormone showed that the removal of [125I]T3 from the serum was very rapid with the t1/2 of about 3.3 hr and the incorporation of the hormone into the brain and brain nuclei were very slow and achieve a maximal value after 4-6 hr of postinjection. The binding of [125I]T3 to the isolated brain nuclei of Singi fish was further studied in vitro. Binding was linearly increased with the increasing concentration of the DNA (nuclei). The binding achieved equilibrium between 15 and 20 min at 27 degrees and was stable at least for 1 hr. The binding was reversible in the presence of excess unlabeled T3. Scatchard analysis showed only a single class of binding sites. The mean dissociation constant (Kd) is 2.15 +/- 0.45 x 10(-10) M and maximum binding capacity (MBC) is 0.044 +/- 0.024 pmol/mg DNA. The relative binding affinities of thyroid hormone analogs for T3 sites were as follows: TRIAC greater than T3 greater than TETRAC greater than T4 greater than reverse T3 greater than T2. These findings were similar to those for other animals. Therefore, the nuclear binding sites in Singi fish brain, as demonstrated, may be regarded as thyroid hormone receptors. PMID- 1874390 TI - Regulation of sexual succession in the protogynous black sea bass, Centropristis striatus (Osteichthyes: Serranidae) AB - Serum levels of 17 beta-hydroxy-4-androstene-3,11-dione (11-KT) and testosterone in the protogynous black sea bass, Centropristis striatus fluctuate annually, correlated with the breeding season. Although serum 11-KT levels in both males and females exhibit seasonality, serum estradiol-17 beta concentrations cycle annually only in the females. Throughout the year, serum estradiol levels in males (127 +/- 56 pg/ml, mean +/- SD) were significantly (P less than 0.05) less than levels in breeding (3,930 +/- 1,390 pg/ml), or nonbreeding females (261 +/- 62 pg/ml). In all female sea bass not undergoing sexual succession, histological examination of the ovary revealed only spermatogonia or ongoing spermatogenesis restricted to the posterior male lamellae; a duct system was nonexistent. In female fish undergoing sexual succession, ovarian tissue was always nonvitellogenic and regressing. Breeding females were not observed to undergo gender change. During sexual succession in the postspawning period, male tissue spread into neighboring female lamellae containing oocytes, gradually replacing them and other female tissue. A male duct system developed on the surface. At any time of year, black sea bass undergoing sexual succession had serum estradiol levels (79 +/- 19 pg/ml) which were significantly less (P less than 0.05) than concurrent female serum estradiol levels. A chi-square test demonstrated that serum estradiol levels in these intersex animals were not significantly different from those of males. The possibility is discussed that sexual succession results from inhibition of ovarian tissue response to steroidogenic gonadotropin. PMID- 1874391 TI - Thyroxine treatment induces changes in hypothalamic gonadotrophin-releasing hormone characteristic of photorefractoriness in starlings (Sturnus vulgaris). AB - Photosensitive intact male starlings were transferred from short days (8L:16D) to 11L:13D for 16 weeks, and were therefore sexually mature. Experimental groups were (i) held under 11L:13D and given exogenous thyroxine dissolved in the drinking water for 6 weeks or (ii) given thyroxine for 6 weeks and then transferred from 11L:13D to long days (18L:6D) for a further 6 weeks, while control groups were transferred to long days (18L:6D) either (iii) for 6 or (iv) for 12 weeks, or were (v) maintained under 11L:13D throughout. Changes in testicular size and plumage molt were monitored at regular intervals during the 12-week period. At the end of the experiment, the birds were killed and hypothalamic gonadotropin-releasing hormone (Gn-RH) content and testicular mass were measured. Treatment with exogenous thyroxine caused rapid testicular regression followed by plumage molt, and after 6 weeks hypothalamic Gn-RH content was much reduced, to an even greater extent than that in control birds exposed to long days for 6 weeks. After 6 weeks of thyroxine treatment, withdrawal of exogenous thyroxine and exposure to long days for a further 6 weeks caused no increase in testicular size, and caused a further reduction in hypothalamic Gn-RH content to a level similar to that in controls after 12 weeks of exposure to long days. The results confirm previous findings that thyroxine induces a state of photorefractoriness in sexually mature starlings and show for the first time that the treatment mimics the effect of long days in reducing Gn-RH content in the hypothalamus. PMID- 1874392 TI - In vitro effect of insulin on the uptake of glucose and alpha-aminoisobutyric acid in the thyroid gland of the turtle (Chrysemys dorbigni). AB - The presence of specific insulin binding sites in the thyroid gland of the turtle Chrysemys dorbigni has been previously reported. The purpose of the present work was to investigate the probable action of insulin on the uptake of [14C]deoxy-D glucose ([14C]DG) and [14C]alpha-aminoisobutyric acid ([14C]AIB) in turtle (C. dorbigni) thyroid glands in vitro. Thyroid fragments (+/- 40 mg) were incubated at 25 degrees in Krebs-Ringer-bicarbonate buffer containing 0.2 microCi of [14C]DG or [14C]AIB without or with bovine insulin at different periods of time. The uptake of [14C]DG and [14C]AIB increased with incubation time. The presence of insulin (7 x 10(-6) M) in the incubation medium during 240 min did not modify the [14C]DG uptake. However if the thyroid fragments were previously incubated with insulin (60 min) and then incubated (240 min) with the same concentration of the hormone, the [14C]DG uptake was markedly increased. This stimulatory effect of insulin was dose-dependent. In similar experimental conditions, insulin also produced a significant increase in the uptake of [14C]AIB. Therefore, these findings strongly support the hypothesis that insulin might exert a direct action on the thyroid function. PMID- 1874393 TI - Effects of castration and androgen treatment on aromatase activity in the brain of mature male Atlantic salmon (Salmo salar L.) parr. AB - Brain homogenates from male Atlantic salmon parr aromatized tritiated androstenedione to estrogens. The aromatase activity in homogenates of whole brains from castrated male parr was lower than that in homogenates from sham operated male parr in autumn. This was also found in homogenates of the telencephalon and diencephalon, but not in homogenates of the tectum opticum. Treatment of castrated males with testosterone (T) and 11-ketoandrostenedione (OA) increased the aromatase activity in whole brains. T, but not OA, also significantly increased aromatase activity in all brain parts. In spring, half a year after the peak breeding period, mature parr males had a lower aromatase activity in telencephalon, diencephalon and tectum than that found in castrated males in autumn, whereas immature males displayed an even lower level of activity. PMID- 1874394 TI - Cloning and characterization of an extracellular temperature-labile serine protease gene from Aeromonas hydrophila. AB - Aeromonas virulence is thought to depend on multigenic functions. The gene for an extracellular protease from Aeromonas hydrophila SO2/2 was cloned in Escherichia coli C600-1 by using pIJ860, bifunctional plasmid, as a vector. The gene encodes for a temperature-labile serine protease (P2) with a molecular mass of approx. 68 kDa which is highly inhibited by PMSF. The gene was expressed in Streptomyces lividans 1326 by transforming protoplasts with the original clone pPA2. We were also able to transfer and express the prt P2 gene in Pseudomonas putida by mating experiments. The protein P2 was secreted into the periplasms of both P. putida and E. coli C600-1 being identical in properties to one of the proteases secreted into the culture supernatant by A. hydrophila SO2/2. PMID- 1874395 TI - Localisation of the aminoglycoside-(3)-N-acetyltransferase isoenzyme II in Escherichia coli. AB - For the location of the aminoglycoside-(3)-N-acetyltransferase isoenzyme II (AAC(3)-II) in the bacterial cell, two strains were studied: Escherichia coli HB101(pJV03), producing the 31-kDa AAC (3)-II enzyme, and E. coli HB101, which served as a control. From each strain five protein fractions were prepared: culture supernatant, and proteins occurring in the periplasm, cytoplasm, inner membrane and outer membrane. All fractions were tested for enzymatic activity of AAC(3)-II. Most of the acetylating activity was found in the cytoplasmic fraction. The distribution of marker enzymes showed a good separation between the periplasmic and the cytoplasmic fraction. PMID- 1874396 TI - Incorporation of fatty acids by Streptococcus mutans. AB - In a series of investigations into the cariogenicity of Streptococcus mutans, we studied the incorporation of exogenous fatty acids with reference to glucosyltransferase secretion and membrane fatty acid changes. When cells were grown with different fatty acids, both saturated and unsaturated fatty acids were readily incorporated into the membrane lipids and were biotransformed and elongated preferentially to the longer 16- and 18-carbon-chain fatty acids. This incorporation and chain-elongation led to significant changes in fatty acids composition. By adding fatty acids to the medium, it was possible to appropriately modify the degree of unsaturation and the relative ratio between specific fatty acids in the membrane lipids of S. mutans. PMID- 1874397 TI - Rates of germ tube formation from growing and non-growing yeast cells of Candida albicans. AB - The rates of germ tube formation from growing and non-growing yeast cells of Candida albicans were investigated using a protocol for dimorphism regulated by temperature and pH. Stationary-phase cells formed germ tubes less rapidly than yeast cells that were preincubated in fresh growth medium prior to induction of dimorphism by an upshift in temperature or pH. On the basis of experiments using inhibitors of macromolecular biosyntheses it is suggested that the accelerated growth kinetics required de novo RNA and protein biosynthesis, but not DNA synthesis. The results suggest that metabolically active yeast cells are better able to undergo dimorphism than non-growing cells. PMID- 1874398 TI - Biochemical and biophysical analysis of plasmid pMJ600-encoded tellurite [TeO2(3 )] resistance. AB - Escherichia coli AB1157, and the transconjugant AB1157 (pMJ600), were used to study the mechanism of tellurite resistance conferred by pMJ600, which contains the tellurite resistance determinant cloned from the IncHI-2 conjugative plasmid pMER610. The transconjugant can tolerate a 100-fold higher concentration of potassium tellurite [K2TeO3] than the plasmid-free strain. Both strains were found to accumulate tellurite irreversibly at equivalent rates, with elemental tellurium being deposited intracellularly, direct efflux of tellurite was not found to contribute to the resistance mechanism. However, under these conditions, growth, protein synthesis and oxygen uptake ceased in AB1157, but-were unaffected in the transconjugant. No NADH- or NADPH-linked reduction of tellurite was detected in crude cell extracts of either strain; however, cell extracts of both reduced tellurite at alkaline pH in the absence of any co-factors. PMID- 1874399 TI - Transformation of 3-chlorodibenzofuran by Pseudomonas sp. HH69. AB - The dibenzofuran-degrading bacterial strain Pseudomonas sp. HH69 showed high oxidative activity towards 3-chlorodibenzofuran (3CDF). During the co-metabolic turnover of 3CDF large amounts of 4-chlorosalicylate and temporarily small amounts of salicylate were excreted. Simultaneously a yellow colour appeared due to the excretion of two polar products. Conversion of 3CDF by a mutant, derived from Pseudomonas sp. HH69 and defective in 2,3-dihydroxybiphenyl-1,2-dioxygenase led to the formation of equal quantities of 4'-chloro-2,2',3-trihydroxybiphenyl (4'CTHBP) and 4-chloro-2,2',3-trihydroxybiphenyl (4CTHBP). Crude extracts of the wild type transformed 4'CTHBP to 4-chlorosalicylate, whilst 4CTHBP was transformed to salicylate. Hence, we propose a non-selective initial attack on both aromatic rings of 3CDF and a degradative pathway for the resulting chlorotrihydroxybiphenyls. PMID- 1874400 TI - Detection and identification of mycoplasmas by amplification of rDNA. AB - Alignment of published 16S rRNA sequences allowed the definition of a pair of oligonucleotides suitable for polymerase chain reaction (PCR). Using this pair of PCR primers, several mycoplasmas including the four human parasites Mycoplasma genitalium, M. hominis, M. salivarium and M. orale were detected. This DNA amplification was restricted to species of the genus Mycoplasma while no cross reaction was observed with DNA from other bacteria and eukaryotic cells. Subsequent analysis of amplified products by either specific oligonucleotide hybridization or dideoxy sequencing specified the identity of the detected mycoplasmas. This method offers a highly discriminating and sensitive assay for the direct detection and identification of these microorganisms without the need for prior cultivation. PMID- 1874401 TI - Characterization of a coproporphyrin-protein complex from Rhodobacter capsulatus. AB - Rhodobacter capsulatus strain AJB530 excretes large amounts of coproporphyrin into the culture supernatant. The coproporphyrin was precipitable with ammonium sulfate, suggesting that it was part of a macromolecular complex. Analysis of an ammonium sulfate fraction indicated that the coproporphyrin was bound to a 66-kDa protein with a pI' of 4.0. The same protein was found in the culture supernatant of the bch+ strain PAS100. PMID- 1874402 TI - The phosphate pool in Escherichia coli THU. AB - The phosphate pool of Escherichia coli was determined as a fraction of the total cell phosphate. This relative pool size was found to be essentially independent of cell age. PMID- 1874403 TI - Host passage-dependent wheat germ agglutinin-binding proteins of Chlamydia trachomatis. AB - Wheat germ agglutinin (WGA)-binding proteins in the highly purified elementary bodies (EB) of Chlamydia trachomatis were detected by an ELISA-like assay of immobilized EB. Trypsin-sensitivity of the WGA-binding moieties was detected only in the chlamydiae grown in HeLa cells. A nonionic detergent, beta-octyl-D glucopyranoside (OG), was used to extract proteins from the purified EB. Proteins in the extract were resolved by SDS-PAGE and probed with 125I-labelled WGA. Several proteins reacted with WGA in a specific manner. Some of these WGA-binding proteins in the EB of serovars L1 and E exhibited altered molecular mass after adaptation in the two alternate hosts, HeLa and McCoy cells. These results suggest that WGA-binding proteins exist in chlamydiae. PMID- 1874404 TI - Novel transferable extended-spectrum beta-lactamase (SHV-6) from Klebsiella pneumoniae conferring selective resistance to ceftazidime. AB - A clinical isolate of Klebsiella pneumoniae sensu lato isolated from throat and a blood culture taken from a neutropenic patient treated for 2 weeks with ceftazidime and vancomycin was resistant to ceftazidime (MIC: 32 micrograms/ml) and moderately susceptible to aztreonam (MIC: 4 micrograms/ml). The isolate contained a plasmid of 180 kb which, when transferred to Escherichia coli by conjugation, conferred resistance to ceftazidime and tetracycline. The transconjugant had decreased susceptibility to ceftazidime (128-fold) and aztreonam (8-fold). Clavulanic acid and sulbactam each inhibited the resistance and clavulanic acid showed a synergistic effect when associated with ceftazidime and aztreonam. An extended-spectrum beta-lactamase with an isoelectric point of 7.6 was detected in the clinical isolates from blood and its transconjugant. This beta-lactamase showed similar substrate and inhibition profiles to SHV-1. In particular it did not hydrolyse ceftazidime. Hybridization with an intragenic probe for SHV-3 indicates that this beta-lactamase is an SHV-type enzyme. We propose that this novel CAZ-type extended-spectrum beta-lactamase be named SHV-6. PMID- 1874405 TI - Susceptibility of iron-loaded Borrelia burgdorferi to killing by hydrogen peroxide and human polymorphonuclear leucocytes. AB - Borrelia burgdorferi grew more slowly in iron-depleted than in iron-sufficient media. The addition of increasing concentrations of iron stimulated borrelial growth and resulted in the intracellular accumulation of this element. Compared with iron-starved borrelia, iron-enriched organisms showed enhanced sensitivity to hydrogen peroxide. Intracellular iron-content did not, however, influence susceptibility to killing by human polymorphonuclear leucocytes [corrected]. PMID- 1874406 TI - Inducing properties of analogs of 2-keto-3-deoxygluconate on the expression of pectinase genes of Erwinia chrysanthemi. AB - In Erwinia chrysanthemi, all the genes involved in pectin degradation are controlled by the negative regulatory gene kdgR. 2-keto-3-deoxy-gluconate (KDG) is the inducing molecule that interacts with KdgR to allow the expression of all the genes of the kdg regulon. The inducing properties on the expression of genes regulated by kdgR of various analogs and derivatives of KDG were tested. All the inducers share the common moiety COOH-CO-CH2-CHOH-C-C included in a pyranic cycle. Our results show that esterification of C1 prevents induction. Presence of a ketone function on C2 and absence of hydroxyl on C3 are necessary for induction. The nature and the configuration of substituent on C5 has no influence on induction. Two compounds have interesting properties: 5-O-methyl-KDG is a gratuitous inducer, and gluconic acid can prevent induction. PMID- 1874407 TI - Evidence for the involvement of acylglycerides on chitin synthetase activity in Candida albicans. AB - The effect of a lipase activity (EC 3.1.1.3) on the chitin synthetase from Candida albicans has been studied, both on the active and the trypsin activated enzyme. Removal of fatty acids from acylglycerides by lipase has an inhibitory effect on the activity as well as on the 'in vitro' activation process by trypsin in the membrane-bound enzyme and in the chitosomes. This would indicate that an adequate lipid environment is required for both the activation process and proper function of the synthetase activity. PMID- 1874408 TI - Nucleotide sequence of two Clostridium thermosulfurogenes EM1 genes homologous to Escherichia coli genes encoding integral membrane components of binding protein dependent transport systems. AB - The complete nucleotide sequence of two genes from Clostridium thermosulfurogenes EM1 homologous to E. coli genes encoding transport proteins was determined by the dideoxy procedure. The genes were cloned from plasmid pCT4, which contains the alpha-amylase gene from C. thermosulfurogenes EM1 as a 2.9-kbp XbaI fragment, inserted into the XbaI site of pUC18, to yield plasmid pCT401. The proteins encoded by the two identified complete ORFs are very hydrophobic and thus are probably integral membrane proteins. They show over 50% similarity to the maltose transport proteins MalF and MalG and to the glycerol-3-phosphate uptake proteins UgpA and UgpE of Escherichia coli. Since these genes are located immediately upstream of the alpha-amylase gene (amyA) of C. thermosulfurogenes EM1, the encoded proteins might be involved in transport of starch degradation products. The genes were tentatively designated amyC and amyD. PMID- 1874409 TI - Alternative NAD(+)-dependent formate dehydrogenases in the facultative methylotroph Mycobacterium vaccae 10. AB - Mycobacterium vaccae 10 growing in methanol medium synthesizes two inducible alternative NAD(+)-dependent formate dehydrogenases (FDH). In the presence of molybdenum, the dominating form of the enzyme is FDHI with Mr 440 kDa and Km 0.32 mM for sodium formate. FDHI reduced ferricyanide as well as NAD+, and it was reversibly inactivated by formate. NAD+ stabilized FDHI against this inactivation. Under conditions of artificial molybdenum deficiency (tungsten in the medium), the second enzyme (FDHII) appeared with Mr about 93 kDa and Km 8.3 mM for sodium formate, and no FDHI activity was detected. FDHII did not reduce ferricyanide and was not inactivated by formate. The activity of FDHI was restored in tungsten-grown cells by pulse addition of molybdenum under conditions of blocked protein synthesis, suggesting the pre-existence of inactive apo-FDHI. PMID- 1874410 TI - The regulation of arginine biosynthesis: its contribution to understanding the control of gene expression. PMID- 1874411 TI - Isolation and characterization of Schizosaccharomyces pombe mutants affected in mitotic recombination. AB - A haploid Schizosaccharomyces pombe strain carrying a heteroallelic duplication of the ade6 gene was used to isolate mitotic recombination-deficient mutants. Recombination between the different copies of the ade6 gene can lead to Ade+ segregants. These are observed as growing papillae when colonies of a suitable size are replicated onto selective medium. We isolated mutants which show an altered papillation phenotype. With two exceptions, they exhibit a decrease in the frequency of mitotic recombination between the heteroalleles of the duplication. The two other mutants display a hyper-recombination phenotype. The 12 mutations were allocated to at least nine distinct loci by recombination tests. Of the eight rec mutants analyzed further, six were also affected in mitotic intergenic recombination in the intervals cen2-mat or cen3-arg 1. No effect on mitotic intragenic recombination was observed. These data suggest that mitotic gene conversion and crossing over can be separated mutationally. Meiotic recombination occurs at the wild-type frequency in all mutants investigated. PMID- 1874412 TI - Dominant and recessive suppressors that restore glucose transport in a yeast snf3 mutant. AB - The SNF3 gene of Saccharomyces cerevisiae encodes a high-affinity glucose transporter that is homologous to mammalian glucose transporters. To identify genes that are functionally related to SNF3, we selected for suppressors that remedy the growth defect of snf3 mutants on low concentrations of glucose or fructose. We recovered 38 recessive mutations that fall into a single complementation group, designated rgt1 (restores glucose transport). The rgt1 mutations suppress a snf3 null mutation and are not linked to snf3. A naturally occurring rgt1 allele was identified in a laboratory strain. We also selected five dominant suppressors. At least two are tightly linked to one another and are designated RGT2. The RGT2 locus was mapped 38 cM from SNF3 on chromosome IV. Kinetic analysis of glucose uptake showed that the rgt1 and RGT2 suppressors restore glucose-repressible high-affinity glucose transport in a snf3 mutant. These mutations identify genes that may regulate or encode additional glucose transport proteins. PMID- 1874413 TI - Interaction of the yeast omnipotent suppressors SUP1(SUP45) and SUP2(SUP35) with non-mendelian factors. AB - The SUP1 and SUP2 genes code for protein factors intimately involved in the control of translational accuracy. The disrupted alleles of these genes confer a recessive lethal phenotype in both [psi+] and [psi-] genetic backgrounds, indicating an essential function for the corresponding proteins. In [psi+] diploids, heterozygous for the SUP1 null allele, several dominant phenotypes were evident with slow growth and inability to sporulate. These dominant phenotypes disappear after transformation with the multicopy plasmid carrying the wild-type allele of the SUP1 gene. Such dominant phenotypes were not observed for the SUP2 null allele. The incompatibility of multicopy plasmids carrying the SUP2 gene with guanidine hydrochloride-curable cytoplasmic factor(s) was also demonstrated. The possible mechanisms of interaction of the SUP1 and SUP2 genes with the [psi] determinant are discussed. PMID- 1874414 TI - Saccharomyces cerevisiae null mutants in glucose phosphorylation: metabolism and invertase expression. AB - A congenic series of Saccharomyces cerevisiae strains has been constructed which carry, in all combinations, null mutations in the three genes for glucose phosphorylation: HXK1, HXK2 and GLK1, coding hexokinase 1 (also called PI or A), hexokinase 2 (PII or B), and glucokinase, respectively: i.e., eight strains, all of which grow on glucose except for the triple mutant. All or several of the strains were characterized in their steady state batch growth with 0.2% or 2% glucose, in aerobic as well as respiration-inhibited conditions, with respect to growth rate, yield, and ethanol formation. Glucose flux values were generally similar for different strains and conditions, provided they contained either hexokinase 1 or hexokinase 2. And their aerobic growth, as known for wild type, was largely fermentative with ca. 1.5 mol ethanol made per mol glucose used. The strain lacking both hexokinases and containing glucokinase was an exception in having reduced flux, a result fitting with its maximal rate of glucose phosphorylation in vitro. Aerobic growth of even the latter strain was largely fermentative (ca. 1 mol ethanol per mol glucose). Invertase expression was determined for a variety of media. All strains with HXK2 showed repression in growth on glucose and the others did not. Derepression in the wild-type strain occurred at ca. 1 mM glucose. The metabolic data do not support- or disprove-a model with HXK2 having only a secondary role in catabolite repression related to more rapid metabolism. PMID- 1874415 TI - Genetic interactions at the FLA10 locus: suppressors and synthetic phenotypes that affect the cell cycle and flagellar function in Chlamydomonas reinhardtii. AB - Through the isolation of suppressors of temperature-sensitive flagellar assembly mutations at the FLA10 locus of Chlamydomonas reinhardtii, we have identified six other genes involved in flagellar assembly. Mutations at these suppressor loci, termed SUF1-SUF6, display allele specificity with respect to which fla10- mutant alleles they suppress. An additional mutation, apm1-122, which confers resistance to the plant herbicides amiprophos-methyl and oryzalin, was also found to interact with mutations at the FLA10 locus. The apm1-122 mutation in combination with three fla10- mutant alleles results in synthetic cold-sensitive cell division defects, and in combination with an additional pseudo-wild-type fla10- allele yields a synthetic temperature-sensitive flagellar motility phenotype. Based upon the genetic interactions of these loci, we propose that the FLA10 gene product interacts with multiple components of the flagellar apparatus and plays a role both in flagellar assembly and in the cell cycle. PMID- 1874416 TI - Three genes which affect founding of aggregations in Polysphondylium pallidum. AB - PN6024 is an extraordinary mutant strain of the cellular slime mold Polysphondylium pallidum, characterized by having defects in many unlinked genes. New strains with altered development appeared spontaneously as aberrant clones of PN6024. Genetic crosses using the macrocyst sexual cycle were used to show that PN6030 (a clone like PN6024 in phenotype) carries mutations at two loci, emm and hge, whereas PN6031 (a clone of altered morphology) carries in addition a mutation at a third locus, mgt. hge and possibly mgt are linked to the mating type locus mat. The relatively high frequency of recombination between mat and hge is strong evidence that meiosis precedes macrocyst germination. The mutant genes themselves are of interest. A major effect of the emm-1 mutation is to remove the requirement for light to trigger aggregation. hge-1 greatly reduces the frequency of aggregation, whereas mgt-1 greatly increases it under standard conditions. None of these mutations interrupts later development leading to stalks and spore cells. It is hypothesized that all three genes act on steps immediately preceding the differentiation of the founder cells which initiate aggregation. PMID- 1874417 TI - Sequence identity in an early chorion multigene family is the result of localized gene conversion. AB - The multigene families that encode the chorion (eggshell) of the silk moth, Bombyx mori, are closely linked on one chromosome. We report here the isolation and characterization of two segments, totaling 102 kb of genomic DNA, containing the genes expressed during the early period of choriogenesis. Most of these early genes can be divided into two multigene families, ErA and ErB, organized into five divergently transcribed ErA/ErB gene pairs. Nucleotide sequence identity in the major coding regions of the ErA genes was 96%, while nucleotide sequence identity for the ErB major coding regions was only 63%. Selection pressure on the encoded proteins cannot explain this difference in the level of sequence conservation between the ErA and ErB gene families, since when only fourfold redundant codon positions are considered, the divergence within the ErA genes is 8%, while the divergence within the ErB genes (corrected for multiple substitutions at the same site) is 110%. The high sequence identity of the ErA major exons can be explained by sequence exchange events similar to gene conversion localized to the major exon of the ErA genes. These gene conversions are correlated with the presence of clustered copies of the nucleotide sequence GGXGGX, encoding paired glycine residues. This sequence has previously been correlated with gradients of gene conversion that extend throughout the coding and noncoding regions of the High-cysteine (Hc) chorion genes of B. mori. We suggest that the difference in the extent of the conversion tracts in these gene families reflects a tendency for these recombination events to become localized over time to the protein encoding regions of the major exons. PMID- 1874418 TI - Length and sequence variation in evening bat D-loop mtDNA. AB - Length variation in D-loop mitochondrial DNA was observed after amplification with the polymerase chain reaction (PCR) in 28% of 195 evening bats, Nycticeius humeralis, from seven colonies. Nucleotide sequences of PCR products show that this heteroplasmy is characterized by an 81-bp region which is tandemly repeated five to eight times. Southern blots using PCR products as probes on HaeIII genomic digests confirm the presence of heteroplasmy. Furthermore, densitometry of electrophoresed PCR products from 109 mother-offspring pairs indicate that heteroplasmy is stably transmitted from mother to offspring with one exception: a heteroplasmic offspring had a homoplastic mother and sib. Nucleotide sequences from this family reveal that a repeat duplication and deletion occurred. The observed mutation rate per generation, mu, for length polymorphism is comparable to an independent estimate, mu = 10(-2), based on hierarchical diversity statistics. With the exception of the repeat nearest the proline tRNA gene, sequence similarities between repeats within bats are consistent with a model of concerted evolution due to unidirectional replication slippage. Selection is inferred to act on the first repeat because in comparison to other repeats it has the least sequence divergence among bats, the fewest transversions, and the lowest minimum free energy associated with folding. PMID- 1874419 TI - Three-locus linkage analysis using recombinant inbred strains and Bayes' theorem. AB - Recombinant inbred (RI) strains are useful in linkage analysis and gene mapping. However, the generally small number of strains in an RI strain set limits the power of RI strains in linkage detection. Several methods for increasing the power of RI strains have been used, including summing data across RI strain sets and excluding linkage to genomic regions. In this paper, Bayesian analysis is applied to three-locus linkage data. This method further increases the power of RI strains to detect linkage and gives estimations of the probability of each of the three possible gene orders if the test locus is linked to the pair of marker loci. Several examples are presented, including reconsideration of the position of the proto-oncogene L-myc on the mouse linkage map. PMID- 1874420 TI - Comparative effects of pollen and seed migration on the cytonuclear structure of plant populations. I. Maternal cytoplasmic inheritance. AB - We explicitly solve and analyze a series of deterministic continent-island models to delimit the effects of pollen and seed migration on cytonuclear frequencies and disequilibria in random-mating, mixed-mating and self-fertilized populations. Given the critical assumption of maternal cytoplasmic inheritance, five major findings are (i) nonzero cytonuclear disequilibria will be maintained in the island population if and only if at least some migration occurs each generation through seeds with nonrandom cytonuclear associations; (ii) immigrant seeds with no cytonuclear disequilibria can strongly affect the genetic structure of the island population by generating significant and long-lasting transient associations; (iii) with all else being equal, substantially greater admixture disequilibria are generally found with higher rates of seed migration into, or higher levels of self-fertilization within, the island population (with the possible exception of the heterozygote disequilibrium); (iv) pollen migration can either enhance or reduce the cytonuclear disequilibria caused by seed migration, or that due to mixed-mating in the absence of seed migration, but the effect is usually small and appears primarily to make a noticeable difference in predominantly outcrossing populations; and (v) pollen migration alone cannot generate even transient disequilibria de novo in populations with completely random associations. This same basic behavior is exhibited as long as there is some random outcrossing in the island population. Self-fertilized populations represent a special case, however, in that they are necessarily closed to pollen migration, and nonzero disequilibria can be maintained even in the absence of seed migration. All of these general results hold whether the population is censused as adults or as seeds, but the ability to detect nonrandom cytonuclear associations can depend strongly on the life stage censused in populations with a significant level of random outcrossing. We suggest how these models might be used for the estimation of seed and pollen migration. PMID- 1874421 TI - Does Xmrk an interesting spot? PMID- 1874422 TI - Regulation of benzodiazepine prescribing practices: clinical implications. AB - In an effort to control prescription abuse of benzodiazepines, the New York State Department of Health (DOH) enacted a regulation requiring the use of triplicate prescriptions for these medications. DOH predicted that this regulation would reduce the overall abuse of benzodiazepines and eliminate widescale organized fraud and abuse without any negative impact or reduced availability to patients. Following implementation of the regulation, the authors reviewed all psychiatric emergency room cases and outpatient clinic walk-in evaluations over a 3-month period in an urban medical center and identified 59 cases in which the use of benzodiazepines was a significant presenting problem. Of these, 24 (41%) were judged to be directly related to the new triplicate regulation. In all but one of these cases the patient presented because of symptoms or concerns directly stemming from the refusal by a clinician to continue prescribing a benzodiazepine in a previously established pattern. Typically, abrupt discontinuation of benzodiazepine treatment led to a withdrawal syndrome and/or the unmasking of a previously treated anxiety disorder. In attempting to redress what are essentially criminal substance abuse problems through the regulation of legitimate clinical practice, regulatory agencies may ultimately deprive patients of appropriate, legitimate, and efficacious treatments. PMID- 1874423 TI - Psychiatric aspects of head and neck surgery. Part II: Body image and psychiatric intervention. AB - Surgery of the head and neck leads to profound changes of body image, including disfigurement and difficulties with verbalization. The psychologic importance of alterations in these areas will be discussed as well as their effect on the conduct of psychiatric treatment. Psychiatric intervention in this population demands an active approach and special preparation for the therapeutic encounter is necessary. PMID- 1874424 TI - Psychopharmacology and neuropsychiatric syndromes in organ transplantation. AB - The physiological imbalances associated with organ insufficiency and the complexity of organ transplant surgery and postoperative care puts patients at risk for psychiatric disorders. The brain is susceptible to a variety of insults as a result of these complex processes, including those secondary to medications and infections. We review literature relevant to organ transplant patients and also include empirical knowledge based on clinical practice. We first describe the physiologic and psychiatric issues for each major organ that is commonly transplanted, including liver, kidney, heart, bone marrow, and pancreas, as well as multiple organ transplantation. We then discuss the pharmacologic treatment and neuropsychiatric side effects of rejection with various immunosuppressants, including cyclosporine, azathioprine, OKT3, FK506, and corticosteroids. Certain bacterial, fungal, viral, and protozoal infections occur more frequently in the transplant population; their relationship to neuropsychiatric dysfunction is discussed. We then present details of psychopharmacotherapy of delirium, other organic mental disorders, depression, mania, anxiety, and insomnia, with attention to drug interactions and differential diagnosis. Particularly cautious monitoring of medication doses and serum levels is recommended in these patients. PMID- 1874425 TI - The ward atmosphere of a child psychosomatic unit: a ten-year follow-up. AB - Using the Ward Atmosphere Scale, we reassessed the ward atmosphere of a psychosomatic unit for children and adolescents that has been operating successfully for 10 years. There was remarkable stability in essential treatment program characteristics despite the complete turnover in patients and a 60% turnover in staff. There was substantial correlation between patient and staff perceptions in 1988 and across time (Spearman's rho: 0.951-0.660, all p values less than 0.05). Patients and staff subgroups differed somewhat in their relative emphases on certain program dimensions but, overall, the program still correlated highly with the therapeutic community cluster described by Moos (Spearman's rho: 0.660-0.809, all p values less than 0.05). This stability was achieved despite multiple health care changes, most notably shortened length of stay. Stability was probably due to high staff/patient ratio, continuity of the medical direction, and focus on milieu maintenance in staff meetings. PMID- 1874426 TI - Brief psychological training for health care professionals dealing with cancer patients: a one-year assessment. AB - The usefulness of psychological training for health professionals dealing with terminally ill cancer patients is becoming more widely recognized, but little has been done to elaborate its content and form. Of special interest is the study of the effectiveness of brief psychological training groups and the quality of treatment to be achieved. The principal aim of the training group assessed here was to develop a better understanding of death and dying issues and ways to cope with them. The present study reports the attitudes of participants, assessed 1 year after the end of training in order to investigate the possible consolidation of the immediate posttraining effectiveness reported previously. Subjects (n = 78) who attended the training groups were compared to a control group (n = 42). Attitudes about oneself, illness and death, occupation, personal growth, and professional relationships were assessed with a semantic differential questionnaire before training, after training, and 1 year later. Results show a significant reduction of the positive effect assessed just after the training. While attitudes moved significantly to the positive pole immediately after the end of the training, 1 year later the reverse phenomenon is noted. These data suggest the necessity for improving the effectiveness of short psychological training proposed to help health care professionals dealing with terminally ill cancer patients. PMID- 1874427 TI - What should British consultation-liaison psychiatry be doing? AB - Despite increasing clinical interest and research consultation-liaison (C-L) services in the United Kingdom are mainly haphazard and unsatisfactory. Although the clinical problems are similar to those in other Western countries, the answers must reflect the British health care system. The national C-L organization must formulate and promote detailed policies for 1) clinical priorities; 2) staffing and other resources; 3) integration with other specialist psychiatric services for local populations and primary care; and 4) persuading other medical organizations to place greater emphasis on psychological skills, training requirements, and practice. Some of our conclusions are parochial, some are generally applicable; others are applicable only to countries with comprehensive health care. PMID- 1874428 TI - Physical illness in children of Holocaust survivors. AB - During medical or psychiatric hospitalization, Nazi Holocaust survivors may display emotional symptoms that reflect the psychological sequelae incurred by their traumatization. What is often less recognized is the idiosyncratic responses that may be seen in the children of these survivors in response to physical illness and hospitalization. Psychiatrists should be alert to the possible effects of Holocaust-related experiences. Awareness of emotional conflicts, defenses, and strengths in these individuals may enhance the therapeutic alliance as well as treatment planning. The author describes two cases illustrating adaptive and maladaptive manifestations of the Holocaust theme in response to medical illness. PMID- 1874429 TI - Delirium after cessation of glucocorticoid therapy. AB - We report here a case of delirium that occurred after discontinuation of glucocorticoid therapy. Administration of hydrocortisone reversed the mental status changes seen in this patient. We review similar reported cases and discuss the direct actions of glucocorticoids on the brain. PMID- 1874430 TI - Bromocriptine associated with postpartum hypertension, seizures, and pituitary hemorrhage. AB - Bromocriptine, an ergot alkaloid dopamine agonist, is a recent common treatment for suppression of lactation in postpartum women. A case is presented of a postpartum woman prescribed bromocriptine for suppression of lactation who developed hypertension, headaches, blurry vision, seizures, and pituitary hemorrhage. Differential diagnosis and a literature review are considered. PMID- 1874431 TI - [Activation of trans-acting transcription factors in T-lymphocytes infected by the intracellular parasitic protozoan Theileria parva]. AB - The intracellular protozoan parasite, Theileria parva, causes a lymphoproliferative disease of T-cells in cattle and uncontrolled lymphocyte proliferation in culture. We have identified and characterized in infected cells the trans-acting transcription factors NF-kappa B, AP1 and NF1 controlling lymphocyte-specific expression of several genes. Theileria infected lymphocytes contain constitutively high levels of active NF-kappa B in nuclear fraction. Factor AP1 had high levels of binding activity in nuclear fraction of these cells only in day 1 after passage. Then AP1 activity decreased rapidly in the course of culture growth. Simultaneously, we observed differential changes in the binding activity of several transcription factors of the NF1 family. Selective killing of the parasite, which leaves the host cells intact, results in a dramatic loss of the transcription factors NF-kappa B, AP1 and NF1 from the nuclear fraction of T cells. At the same time, the activity of TATA-box binding proteins did not change significantly following the theilericidal drug treatment. We propose that high levels of activated transcription factors NF-kappa B, AP1 and NF1 are maintained by the presence of parasite in infected T-cells. PMID- 1874432 TI - [Effectiveness of chemical mutagenesis in multiple damage to one or both strands of plasmid DNA]. AB - Methods for site-directed multiple modification of DNA have been developed and used for modification of either one or two strands of plasmid DNA. Plasmid DNAs modified in the region of the tet gene were transformed into Escherichia coli cells and Tet colonies were screened. It was shown that multiple lesions in one DNA strand performed using either N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or sodium bisulfite were effectively repaired in the cell by error-free mechanism. In contrast, modification of two DNA strands led to induction of mutations. The efficiency of mutagenesis in the case of modification of a local region of one DNA strand with sodium bisulfite and modification of the other strand with MNNG was 1.1-7.9%. Mutations were analysed by restriction mapping and sequencing. All of them were G----A transitions. PMID- 1874433 TI - [Inversion polymorphism in malaria mosquito Anopheles messeae. Part X. Resistance of larvae with different genotypes to toxins of crystal-forming bacteria Bacillus thuringiensis subsp. israelensis (serovar H14)]. AB - Insensibility of larvae with different chromosomal inversions to the toxins of Bacillus thuringiensis subsp. israelensis (Bti) was examined. It has been shown that larvae with inversion combinations XL0(XL1)2R0-3R0-3L0 had greater variability after treatment with Bti than larvae with inversions XL1(XL2)2R1-3R1 3L1(3L0). The former inversion combinations were previously shown to dominate in the south of the species area and to be supported by K-selection. The latter inversion combinations form "northest" karyotypes and are supported by r selection. It is obvious that genetic effects of treatments with Bti depend on the population's structure and the directions of natural selection. The decrease in the level of heterozygotes after treatment of larvae with Bti reflects destruction of the system of genetic homeostasis in the natural populations of A. messeae. PMID- 1874434 TI - [Chiasmata distribution in the normal karyotype of mice]. AB - The number of chiasmata per cell and variance of chiasmata numbers were studied, as well as the recombinational interaction between different bivalents in CBA/Lac mice male line. No competition of bivalents for chiasmata was discovered in mice; at the same time, the chiasmata within one arm of the chromosome interfere with each other. The number of chiasmata per bivalent is estimated for each chromosome independently. The number of chiasmata per chromosome is limited both from below (minimum one chiasma independently of its size) and from above (positive interference of chiasmata). PMID- 1874435 TI - [Synapsis and chiasma distribution in mice heterozygous for translocations in chromosomes 16 and 17]. AB - Electron microscopic analysis of synaptonemal complexes and analysis of chiasmata distribution in male mice heterozygous for Robertsonian translocation T(16; 17)7Bnr - (Rb7), for synaptonemal reciprocal translocation T(16;17)43H - (T43), in double heterozygotes for these translocations and in males with partial trisomy of the proximal region of chromosome 17 was carried out. Synaptic disturbances around the breakpoints of the translocations, such as asynapsis of homologous regions of partners and non-homologous synapsis of centromeric regions of acrocentric chromosomes, were revealed. Synaptic regularity in the proximal part of the chromosome 17 appeared to be affected by no t12 haplotype. Good coincidence between sizes of mitotic chromosomes and corresponding lateral elements of synaptonemal complexes was found for all chromosomes, with the exception of Rb7 in trisomics. In the latter karyotype, the proximal part of chromosome 17 involved in Robertsonian fusion seems to be shortened in the course of zygotene and never synapted with homologous segment of neither the acrocentric chromosome 17 nor large product of reciprocal translocation. Drastic increase in chiasmata frequency in the proximal part of chromosome 17 was revealed in heterozygotes for T43H and in trisomics, as compared with the double heterozygotes Rb7/T43. The latter finding was explained by the existence of two independent pairing segments in the former karyotypes. PMID- 1874436 TI - [Brain adrenoreceptors in rats with inherited arterial hypertension due to emotional stress]. AB - For the study of genetic and physiological mechanisms of inherited stress sensitive arterial hypertension, specific binding of ligands of alpha 1-, alpha 2 and beta-adrenoceptors was measured in 2 strains of rats: Wistar normotensive and ISSAH rats (rats with inherited stress-sensitive arterial hypertension). The maximal binding sites (Bmax) and apparent dissociation constants (Kd) were studied with the alpha 1-adrenergic antagonist 3H-prazosin, alpha 2-adrenergic agonist 3H-clonidine and 3H-dihydroalprenolol, a beta 1-receptor antagonist. Four brain regions were investigated: frontal cortex, hypothalamus, pons and medulla oblongata. In comparison with normotensive controls, hypertensive rats had significantly greater density of the alpha 1-adrenoceptors in the medulla oblongata. However, the number of hypothalamic alpha 1-adrenoceptors was significantly reduced in these animals. The same significantly lower alpha 2 adrenoreceptor density was found in the hypothalamus and the pons, and lower, beta-adrenoceptors density in the medulla oblongata. It was concluded that brain adrenoceptors are involved in the mechanisms of development of inherited stress sensitive hypertensive syndrome. PMID- 1874437 TI - [Genetic determination of rheumatoid arthritis. Distribution of certain Mendelian markers in the light of correspondence of the disease heritability to the model of single autosomal two-allele locus with incomplete penetrance]. AB - The study on the nature of distribution of certain mendelian markers aimed at specifying their role in determination of rheumatoid arthritis disease was carried out, based on the material from the Family Data Bank of the Department of Epidemiology and Genetics of the rheumatic diseases in this institute comprising data on 200 families of patients with definite rheumatoid arthritis (RA). Antigens of HLA-system (the loci A, B, DR), ABO blood groups, Rh, MN and P, phenotypes of acid erythrocyte phosphatase and the types of haptoglobin were studied. Based on the data from this and the previous studies, it is established that the steadiest deviations of the RA patients groups from the general population concerned the frequency of HLA A11, B12, B27 and DR4, blood group P and phenotypes of the acid erythrocyte phosphatase. When using additional controls--a group of healthy mothers of women-probands from the families with the type of marriage "healthy x healthy", and analysing some pair combinations of the HLA system antigens, it was demonstrated that the most clearly their role in formation of the disease display the antigens DR4, and in their absence--DR3, and B12, whereas accumulation of A11 and B27 depended on the presence of other antigens of HLA loci--A and B. Taken together, these data may imply that genetic markers under study serve, when in certain combinations, as "modifiers" of the major gene, or, in a general case, of major genes of multifactorial disease affecting its appearance and clinical manifestations. PMID- 1874438 TI - [Frequency criterion of choice of surname for the study of the genetic structure of the population]. AB - On the example of 7 populations of the regional level allowability of using surnames with frequencies exceeding 0.001 in adequate estimation of the population structure indices is shown. The correlation coefficient between genetical distances calculated with the help of all surnames in the list, and those estimated using only frequent surnames was more than 0.9 in all populations studied, values of the correlation coefficient analogous to the FST statistics of Wright being 0.76 to 0.97. PMID- 1874439 TI - Genomes as smart systems. PMID- 1874440 TI - From genes to phenotype: dynamical systems and evolvability. PMID- 1874441 TI - Fluctuation analysis: the effect of plating efficiency. AB - This paper supplements an earlier paper which explained how to calculate the probability distribution of the number of mutants that would be observed in a fluctuation test experiment. The formulas in that work give the distributions to be expected under a wide variety of experimental conditions, but the method it uses when only a fraction of the mutants will produce visible colonies are clumsy and inefficient. Here I describe efficient procedures for dealing with that case, provided that the mutation rate per cell division remains constant during the experiment. PMID- 1874442 TI - Sequence requirements for the stimulation of gene amplification by a mammalian genomic element. AB - HSAG-1 is a 3.4-kb genomic element from a human chronic lymphocytic leukemia- Chinese hamster ovary (CHO) hybrid cell line shown to stimulate the amplification of expression vectors in cis when transfected into a variety of cell lines [McArthur and Stanners, J. Biol. Chem. 266 (1991) 6000-6005]. Subfragments of HSAG-1 were tested for amplification activity by insertion into the vector, pSV2DHFR. The results suggest that multiple positive- and negative-acting elements were present that influenced amplification activity. The deletion of regions believed to contain positive-acting elements decreased or abolished the amplification stimulatory activity of the most active 1.45-kb fragment, supporting this hypothesis. The construction of composite sequences containing multiple positive elements and lacking negative elements, however, failed to enhance the activity; maximum activity was obtained only with the original intact configuration of elements. Two of two CHO HSAG-1-like elements tested had an activity equivalent to HSAG-1, while one of 24 random CHO genomic fragments tested had an activity as high as HSAG-1. The combination of sequence and structural features needed to affect the frequency of gene amplification may therefore be quite common in the mammalian genome. PMID- 1874443 TI - Cloning and characterization of the murine promoter for the colony-stimulating factor-1-encoding gene. AB - Colony-stimulating factor-1 (CSF-1 or M-CSF) is required for the growth and differentiation of macrophage progenitors, and for the survival of mature macrophages. Expression of the CSF-1 gene in monocytes and fibroblasts is controlled at both the transcriptional and post-transcriptional levels. To study the molecular mechanisms which mediate changes in CSF-1 expression, the 5' promoter region of the mouse CSF-1 gene was cloned. A high degree of structural and sequence similarity between the mouse and human CSF-1 genes was observed. A transcription start point was located 182 bp upstream from the start codon. Several sequences homologous to known cis-acting elements were identified in the 5'-flanking region. The CSF-1 promoter region was able to direct expression of a linked reporter gene in C3H10T1/2 mouse embryo fibroblasts. Deletion in the CSF-1 promoter region between bp -774 and -629 resulted in a significant decrease in promoter activity. The identification of a functional promoter for CSF-1 will serve as a valuable tool for studying the regulation of CSF-1 expression. PMID- 1874444 TI - The porcine tumor necrosis factor-encoding genes: sequence and comparative analysis. AB - We have cloned and sequenced a 10.22-kb fragment of the genomic locus of the porcine tumor necrosis factor-encoding genes, TNF-alpha and TNF-beta. A liver genomic DNA library, partially digested with Sau3AI, was cloned into the phage lambda EMBL4 and screened with a porcine TNF-alpha cDNA probe. Analysis showed that both the TNF-alpha and TNF-beta genes were present on the cloned fragment. In addition, the cloned fragment contained about 2 kb of repetitive sequences 5' to the TNF-beta gene. The TNF genes are arranged in a tandem repeat, as is the case for the human, mouse and rabbit TNF genes. The comparison of both genes with their human homologues displayed a considerable degree of conservation (80%), suggesting an equal evolution rate. PMID- 1874445 TI - Isolation and characterization of cDNAs encoding beta A2- and beta A4 crystallins: heterologous interactions in the predicted beta A4-beta B2 heterodimer. AB - Except for the two acidic chains, beta A2 and beta A4, the primary structures of all bovine beta-crystallins have previously been elucidated, either by direct protein sequencing or prediction from cDNA sequencing. Both beta A2 and beta A4 were found to be synthesized in half-year-old calf lenses and are therefore likely to be present in a cDNA bovine library constructed from mRNA isolated from lenses of that age. A large number of cDNA clones was screened with all available crystallin, actin, vimentin and lens membrane protein MP26 probes and finally with a randomly primed mRNA probe. Clones positive for the latter, but negative for known lens proteins, were isolated and sequenced. beta A2, comprising 197 aa, and beta A4, comprising 209 aa, were identified. Both proteins have a conserved two-domain structure and an N-terminal extension which is variable. A three dimensional model of the structure of beta A4 was made based on the coordinates of one subunit from the beta B2 dimer which has recently been solved using x-ray diffraction techniques. The resulting heterodimer structure, together with the compiled bovine beta-crystallin sequences, was used to indicate those regions of the sequences which distinguish acidic from basic beta-crystallins with a view to defining structural features necessary for subunit recognition in beta-crystallin aggregates. With the aid of the present data, the complete evolutionary tree of the bovine beta-crystallin family has been constructed, which confirms the early separation of the genes encoding the three acidic and the three basic beta crystallins. PMID- 1874446 TI - The CpG island in the 5' region of the G6PD gene of man and mouse. AB - The nucleotide (nt) sequence of the entire CpG island in the 5' region of the human glucose-6-phosphate dehydrogenase-encoding gene (G6PD) and of the corresponding region in mouse was determined. In comparison to the human gene, the 5' region of the mouse G6PD gene has highly reduced G + C and CpG dinucleotide content, but maintains the functional features of a CpG island, as it is differentially methylated on the active vs. the inactive X chromosome. In addition to the expected conservation of exons, nt sequence comparison showed that several boxes are highly conserved between the two species in the 5' flanking DNA and in the first intron. Moreover, the conservation of the position of most CpG dinucleotides in the promoter region and in one of the upstream boxes, at about -900, gives support to the hypothesis that, in each island, specific CpGs play a major role in the regulation of gene expression. PMID- 1874447 TI - Isolation and characterization of human thioredoxin-encoding genes. AB - Thioredoxin (Trx) has recently been demonstrated to be an essential component of the early pregnancy factor activity of pregnancy serum. Here, we report the structure and sequence of human Trx-encoding genes (Trx) by analysis of genomic clones. The Trx gene extends over 13 kb and consists of five exons encoding a 12 kDa protein. A 700-bp fragment upstream from the start codon functions as a promoter when inserted in front of a human growth hormone-encoding reporter gene in tissue-culture cells. This promoter region is very G + C rich and does not contain a classical TATA or CCAAT box, but has three consensus sequences for high affinity Sp1 binding. Southern analysis demonstrated the presence of several Trx genes in the human genome. The number includes at least one inactive copy as shown by the isolation and sequencing of an inactive pseudogene. PMID- 1874448 TI - Nucleotide sequences of the mitochondrial genes trnS(TGA) encoding tRNA(TGASer) in Oenothera berteriana and Arabidopsis thaliana. AB - The genes encoding tRNA(TGASer) have been investigated in the mitochondrial (mt) genomes of Oenothera berteriana and Arabidopsis thaliana. Sequence analysis shows four nucleotide (nt) differences between the two dicots, but only two differences between each dicot and the available monocot sequences. Similarity comparisons identify these genes as encoding a native mt tRNA(TGASer), with less than 77% of the nt identical to the corresponding chloroplast tRNAs. PMID- 1874449 TI - The cDNA sequence and primary structure of the chicken transferrin receptor. AB - Recombinant cDNA clones encoding the chicken transferrin receptor (cTR) have been isolated and sequenced. Comparison of the deduced primary structure of cTR with those of the human transferrin receptor (hTR) and mouse transferrin receptor (mTR) shows that their size, hydropathy profile, location of sites for posttranslational modifications, and domain organization are highly similar. The cytoplasmic domain of cTR contains the motif Tyr-Xaa-Arg-Phe (YXRF) that is the recognition signal for high-efficiency endocytosis of hTR. The cTR has several highly conserved regions within its extracellular domain, including those flanking the putative N-glycosylation sites. Overall, however, the extracellular domain of cTR is only 53% identical to the extracellular domains of hTR and mTR. The cTR also lacks three of the six Cys residues found in the extracellular domains of the mammalian TRs. These differences can account for functional and structural properties that distinguish cTR and mammalian TRs. PMID- 1874450 TI - Isolation and analysis of a human cDNA highly homologous to the yeast gene encoding L17A ribosomal protein. AB - A cDNA from human brain poly(A)+RNA with significant similarity to the gene encoding yeast L17A large subunit ribosomal (r) protein (L17A) was isolated using the polymerase chain reaction. The deduced amino acid (aa) sequence of 140 aa (calculated pI of 10.79) exhibits a 78% similarity to that of the yeast L17A r protein (88% when conservative aa replacements are considered as well). This indicates that L17A is one of the best conserved r-proteins and therefore may play a critical role in ribosome function. In contrast to its eubacterial and chloroplast counterparts, human L17A contains an N-terminal extension of 19 aa which may be involved in nuclear targeting of the r-protein. Approximately five to seven genes in mammalian genomes give strong hybridization signals when probed with the human L17A homologue cDNA. Whereas the L17A homologue was found to be expressed at similar levels in several human tissues as a transcript of 600 nucleotides, a several-fold higher transcript level was detected in the rapidly growing neuroblastoma cell line, SK-N-BE. PMID- 1874452 TI - The role of high energy electrons in the treatment of cancer. 25th annual San Francisco Cancer Symposium. San Francisco, California, February 9-11, 1990. PMID- 1874451 TI - Nucleotide sequences of two members of the chicken H3 histone-encoding gene family. AB - The nucleotide sequences of two genes (H3-II and H3-III) from the chicken H3 histone-encoding gene family have been determined. H3-II and H3-III, respectively, possess possible AP-1- and Sp1-binding sequence elements of the forms 5'-CGAGTCAG and 5'-GGGCGGG, whereas all three H3 genes, including the previously sequenced H3-I gene, encode the same amino acid sequence. PMID- 1874453 TI - Milestones in therapeutic radiology. PMID- 1874454 TI - Absorption, transport and metabolism of vitamin E. AB - Vitamin E includes eight naturally occurring fat-soluble nutrients called tocopherols and dietary intake of vitamin E activity is essential in many species. alpha-Tocopherol has the highest biological activity and the highest molar concentration of lipid soluble antioxidant in man. Deficiency of vitamin E may cause neurological dysfunction, myopathies and diminished erythrocyte life span. alpha-Tocopherol is absorbed via the lymphatic pathway and transported in association with chylomicrons. In plasma alpha-tocopherol is found in all lipoprotein fractions, but mostly associated with apo B-containing lipoproteins in man. In rats approximately 50% of alpha-tocopherol is bound to high density lipoproteins (HDL). After intestinal absorption and transport with chylomicrons alpha-tocopherol is mostly transferred to parenchymal cells of the liver were most of the fat-soluble vitamin is stored. Little vitamin E is stored in the non parenchymal cells (endothelial, stellate and Kupffer cells). alpha-Tocopherol is secreted in association with very low density lipoprotein (VLDL) from the liver. In the rat about 90% of total body mass of alpha-tocopherol is recovered in the liver, skeletal muscle and adipose tissue. Most alpha-tocopherol is located in the mitochondrial fractions and in the endoplasmic reticulum, whereas little is found in cytosol and peroxisomes. Clinical evidence from heavy drinkers and from experimental work in rats suggests that alcohol may increase oxidation of alpha tocopherol, causing reduced tissue concentrations of alpha-tocopherol. Increased demand for vitamin E has also been observed in premature babies and patients with malabsorption, but there is little evidence that the well balanced diet of the healthy population would be improved by supplementation with vitamin E. PMID- 1874455 TI - Free radical-induced liver injury. II. Effects of intraperitoneally administered 2,2'-azobis(2-amidinopropane) dihydrochloride on the fatty acid profiles of hepatic triacylglycerol and phospholipids. AB - Liver injury induced by the radical initiator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and carbon tetrachloride (CCI4) was examined by the analysis of lipids in the liver of rats. Increased triacylglycerol (TAG) was found in the liver within 24 hr following injection of these drugs. In AAPH treated and CCI4-treated rats, it was 2.1 and 1.8 times that in the controls, respectively. TAG-palmitate and -oleate were found at particularly increased levels, while polyunsaturated fatty acid profiles of hepatic phospholipids were essentially the same for the treated and untreated rats. It is evident from these findings that radical initiators cause no decrease in polyunsaturated fatty acids in hepatic lipids, but accumulate TAG in the liver. Such a condition is the equivalent of liver injury in the rats in whose diets vitamin E has long been deficient. PMID- 1874456 TI - Comparative study on the influence of two 2-chloroethylnitrosoureas with different carbamoylating potential towards glutathione and glutathione-related enzymes in different organs of the rat. AB - The influence of two CNUs with similar alkylating but strongly different carbamoylating activity towards the glutathione system was investigated in different organs. Both CNUs influence the glutathione system of the bone marrow in a similar manner, irrespective of their carbamoylating potential. In contrast, glutathione reductase activity in the other organs was strongly decreased by the potent carbamoylator BCNU, whereas no or only minor effects were produced by its weakly carbamoylating counterpart HECNU. The results confirm that bone marrow toxicity of CNUs primarily results from alkylation and not from carbamoylation. Other organ-related toxic effects, however, are probably a result of carbamoylating reactions exerted by BCNU. This applies especially to lung toxicity that has been observed frequently as a major side effect in clinical trials with BCNU. PMID- 1874457 TI - The role of histidine residues in the nonenzymic covalent attachment of glucose and ascorbic acid to protein. AB - Copper ions have been suggested to play a role in the non-covalent glycosylation (glycation) of proteins via transition metal-catalysed oxidations. We have further investigated "autoxidative glycosylation" by comparison of the behaviour of dog and bovine serum albumin with respect to the oxidative reactions of glucose and ascorbate. The proteins possess similar numbers of total amino residues available for glucose attachment but dog serum albumin contains fewer histidine groups and also lacks a high affinity copper-binding site. We find that the higher copper-binding capacity of bovine serum albumin is reflected in a lower rate of ascorbate oxidation as well as less protein oxidative damage than is the case for dog serum albumin. We also observe that modification of bovine serum albumin histidine groups by diethylpyrocarbonate enhances ascorbate mediated protein fluorophore formation. PMID- 1874458 TI - Effect of zinc-carnosine chelate compound (Z-103), a novel antioxidant, on acute gastric mucosal injury induced by ischemia-reperfusion in rats. AB - The protective effect of a novel synthetic zinc-carnosine chelate compound, zinc N-(3-aminopropionyl)-L-histidine (Z-103), on the gastric mucosal injury induced by ischemia-reperfusion was studied in rats. Ischemia and reperfusion injury was produced on the rat stomach by applying a small clamp to the celiac artery for 30 min and by removal of the clamp for 30 min. The decrease in the gastric mucosal blood flow was not influenced by the treatment with Z-103. The increase in total area of the erosions on the stomach after ischemia-reperfusion and the increase in lipid peroxides in the gastric mucosa were significantly inhibited by the oral administration of Z-103. In addition, Z-103 inhibited lipid peroxidation of rat brain homogenate and liver microsome in vitro. These results suggest that the protective effect of Z-103 against the aggravation of gastric mucosal injury induced by ischemia-reperfusion may be due to its inhibitory effect on lipid peroxidation. PMID- 1874459 TI - [The protective effect of (4R)-hexahydro-7, 7-dimethyl-6-oxo-1, 2, 5-dithiazocine 4-carboxylic acid (SA3443), a novel cyclic disulfide, on acetaminophen-induced liver injury]. AB - Effects of (4R)-hexahydro-7, 7-dimethyl-6-oxo-1, 2, 5-dithiazocine-4-carboxylic acid (SA3443) on acetaminophen-induced liver injury were investigated in BALB/c mice. SA3443 (30-300 mg/kg, p.o.) dose-dependently suppressed the elevation of serum transaminase activities and the histological changes of liver induced by acetaminophen (150 mg/kg, p.o.). The compound at the same doses also reduced the mortality due to the lethal acute hepatic failure induced by acetaminophen (350 mg/kg, p.o.). Other hepatoprotective agents, cianidanol (500 mg/kg, p.o.), malotilate (100 mg/kg, p.o.), grycyrrhizine (10 mg/kg, i.p.) and cysteine (300 mg/kg, p.o.) similarly reduced it. SA3443 had no effect on glutathione (GSH) contents in the liver of normal mice, but it dose-dependently suppressed the decrease of GSH contents in the liver of BALB/c mice treated with acetaminophen. These results suggest that SA3443, a novel cyclic disulfide, provides considerable protection against acetaminophen-induced liver injury and that one of the modes of the hepatoprotective action of this compound is suppression of the decrease of GSH contents in the liver. PMID- 1874460 TI - [A decrease in the wet-dog shakes response to the second administration of kainic acid in juvenile rats]. AB - The effect of an intermittent administration of kainic acid on the KA-induced behavior, scratching, wet-dog shakes and limbic seizures was studied in the rat. Nine mg/kg kainic acid was injected i.p. at 3, 7, 14 or 21 days after the priming with the same dose of kainic acid at 25 days of age. There was no significant effect of KA-priming on the onset time of scratching. The frequency of wet-dog shakes decreased significantly in all the KA-primed rats. Fourteen day-priming of kainic acid was most effective for reducing the wet-dog shakes response. The onset time of limbic seizures tended to be shorter in all the KA-primed groups; seven day-priming resulted in a significant decrease. Histological findings showed a delay in the formation of dendritic processes of pyramidal cells in the CA3 area of the hippocampus. The results indicated that an intermittent administration of kainic acid with an interval of 3 to 21 days induces a marked tolerance in the wet-dog shakes response to kainic acid in juvenile rats, while no change in the scratching and an acceleration of the onset of limbic seizures were shown, implying that different neuronal systems are involved in these three behaviors induced by kainic acid. PMID- 1874461 TI - [Preventive effects of green tea extract on lipid abnormalities in serum, liver and aorta of mice fed a atherogenic diet]. AB - This study examined the preventive effects of green tea extract on hyperlipidemia and lipid accumulation in the liver and aorta of mice fed an atherogenic diet enriched with 1.5% cholesterol, 0.5% cholic acid and 5% linoleic acid for a period of 14 weeks. The animals were given green tea extract in drinking water at doses of 50, 100 and 200 mg/kg/day. Treatment with green tea extract prevented the increase of serum cholesterol induced by the atherogenic diet 6 weeks after the start of the experiment. The increase of serum lipid peroxides was markedly prevented in a dose-related manner. The green tea extract also tended to prevent the increase of serum phospholipid and the decline of lecithin: cholesterol acyltransferase, but could not prevent decreases in serum triglycerides and high density lipoprotein cholesterol. As for liver cholesterol, its content, particularly free cholesterol, in mice fed the atherogenic diet could be prevented from increasing by treatment with the extract at 50 and 100 mg/kg/day. In addition, the increase of aortic cholesterol, particularly esterified cholesterol, could be prevented in a dose-related manner. These results suggest that green tea has anti-atherosclerotic activity. PMID- 1874462 TI - [Effects of scopolamine upon delayed radial-arm maze performance in rats]. AB - Behavioral impairment induced by the muscarinic anticholinergic drug, scopolamine (SCP) has been widely used to make preclinical evaluation of nootropic drugs. To further investigate the disruptive effect of SCP on memory-related behavior, male Wistar-Imamichi strain rats were tested in the 8-arm radial maze task with a delay interval between choices 4 and 5. In this task, the animals were first allowed to obtain 4 food rewards out of 8 arms and then removed from the maze. They were replaced on the maze to collect the remaining 4 pellets after a delay interval, during which they were kept in their home cages. In experiment 1, a 1-6 hr delay interval was imposed. SCP (0.5 mg/kg, i.p.) was administered immediately after choice 4. In experiment 2, a delay interval was always 4 hr, but SCP was administered 0-2 hr after choice 4. In both experiments, SCP significantly reduced the number of correct choices in choices 5-8, but did not show any effects depending on delay intervals or drug-administration time. These results suggest that the performance deficits induced by SCP might be due to its effects on the primary stage of information processing rather than those on the consolidation or storage process of memory. PMID- 1874463 TI - Early changes in the forestomach of rats, mice and hamsters exposed to dietary propionic and butyric acid. AB - Groups of five male and five female rats, mice and hamsters were fed diet containing 4% propionic or butyric acid for 7 days. Evidence of damage and cellular proliferation in the epithelium of the forestomach and limiting ridge was detected in all three species. Changes were particularly marked in animals fed butyric acid diet and rats appeared to be the most sensitive species. It is postulated that tumours of the forestomach reported in rats after long-term feeding of propionic acid diet may be a consequence of continued damage and repair, and that butyric acid, which occurs naturally in foods at concentrations up to 5%, would be at least as potent as propionic acid if similarly tested. PMID- 1874464 TI - Lack of bladder carcinogenicity of dietary sodium saccharin in analbuminaemic rats, which are highly susceptible to N-nitroso-n-butyl-(4-hydroxybutyl)amine. AB - A previous 1-wk study measuring the agglutinability of bladder epithelial cells by concanavalin A had suggested a high susceptibility of analbuminaemic rats to bladder carcinogenesis by sodium saccharin (Honma et al., Cancer Letters 1983, 19, 7). A long-term study was conducted to confirm the results of this short-term assay. Sodium saccharin was administered at 5% in the diet to groups of 35 male analbuminaemic rats and 36 male rats of the Sprague-Dawley strain. No bladder carcinomas nor precancerous lesions were observed in any of the rats exposed to sodium saccharin. The discrepancy between the results of the agglutination assay and the long-term experiment might be attributable to a sharp increase in urine volume in analbuminaemic rats during the first week of treatment. The resultant distension of the bladder wall might make the epithelial cells more susceptible to concanavalin A agglutination. The results indicated no demonstrable bladder carcinogenicity of sodium saccharin in analbuminaemic rats and excluded the possibility that these particular mutant rats could be useful animals for shorter duration screening for bladder carcinogens. PMID- 1874465 TI - An experimental approach to identifying the genotoxic risk from cooked meat mutagens. AB - In order to define the toxicological risk to the human population from the chemical compounds formed during the process of cooking animal meat, which have been described as possessing mutagenic, genotoxic and carcinogenic activities, an extensive study was undertaken of cooked meat extract and two cooked meat mutagens, 2-amino-3-methylimidazo(4,5-f)quinoline (IQ) and 2-amino-3,8 dimethylimidazo(4,5-f)quinoxaline (MeIQx). The study involved toxicokinetics and mouse-tissue distribution studies of the two chemicals, in vitro and in vivo mutagenicity/genotoxicity analyses (i.e. the detection of gene mutations, chromosome aberrations and micronuclei in mouse bone marrow cells, and mouse urine and faeces mutagenicity tests), as well as in vivo protein and DNA binding assays. IQ and MeIQx were found to be positive for the induction of gene mutations in Salmonella typhimurium TA98, but not in Chinese hamster V79 cells; IQ only was found to be positive for the induction of chromosome aberrations in Chinese hamster ovary cells and cultured human lymphocytes. IQ and MeIQx were negative for the induction of micronuclei in mice treated with 40 mg chemical/kg body weight; the lowest effective dose administered to the mice that produced mutagenic urine was 0.4 mg IQ/kg body weight and 0.04 mg MeIQx/kg. A dose of 40 mg IQ/kg, given orally by gavage to mice, produced an excretion of 1-4% of the applied dose in the urine and 0.1-2% of the applied dose in the faeces, when evaluated chemically or mutagenically. The number of DNA adducts in the liver correlated with the dose of IQ or MeIQx administered to the mice. All the data have been used for defining a possible risk estimate to the human population as a consequence of a cooked meat diet. PMID- 1874466 TI - Influence of dietary protein and gut microflora on endogenous synthesis of nitrate induced by bacterial endotoxin in the rat. AB - Germ-free (GF) rats were maintained on a diet marginally adequate in protein, with and without a supplement of NH4Cl. Their urinary excretion of total nitrogen, nitrate, urea and creatinine was measured before and for 4 days after injection of Escherichia coli endotoxin (lipopolysaccharide; LPS). Although more nitrogen was excreted by rats on the diet supplemented with NH4Cl, nitrate excretion was increased to a similar extent in rats on both diets. This suggests that oxidation of ammonia released by deamination of amino acids is an unlikely pathway of nitrate synthesis. In a second experiment, nitrate excretion before and after injection of LPS was measured in GF and conventional (CV) rats given high- or low-protein diets. Urinary 3-methylhistidine (3MH) was measured as an index of breakdown of tissue protein. In both environments, nitrate excretion was significantly greater, before and after LPS administration, by rats on the high protein diet than by their counterparts on the low-protein diet, and was generally greater by GF than by CV rats. Since only small, non-significant rises in urinary 3MH were observed after LPS treatment, it was concluded that the bulk of the nitrogen required for nitrate synthesis in response to endotoxin is derived from dietary protein rather than from nitrogenous products of tissue breakdown. PMID- 1874467 TI - Chemoprotective and hepatic enzyme induction properties of indole and indenoindole antioxidants in rats. AB - Three indole antioxidants were compared for their efficacy to inhibit lipid peroxidation, prevent chemical hepatotoxicity and induce enzyme systems involved in the biotransformation of xenobiotics. The dietary indolyl compound indole-3 carbinol (I-3-C), and the synthetic compounds 5,10-dihydroindeno[1,2-b]-indole (DHII) and 4b,5,9b,10-tetrahydroindeno[1,2-b]indole (THII) inhibited carbon tetrachloride (CCl4)-initiated lipid peroxidation in rat-liver microsomes, with the order of efficacy THII greater than DHII = butylated hydroxytoluene (BHT) much greater than I-3-C. Each of the indole compounds protected isolated rat hepatocytes against toxicity by CCl4, N-methyl-N'-nitro-N-nitrosoguanidine and methylmethanesulphonate (THII congruent to DHII much greater than I-3-C). In vivo administration of the indole compounds 1 hr before treatment with CCl4 protected against hepatotoxicity (THII greater than DHII greater than I-3-C). For the enzyme induction studies, phenobarbital and beta-naphthoflavone were used as standards, with corn-oil vehicle controls. The compounds were administered by gavage at 50 mg/kg body weight/day for 10 days. I-3-C produced increases in levels of hepatic cytochromes P-450 and ethoxyresorufin O-deethylase (EROD) activity, as well as in UDP-glucuronosyl transferase (UDPGT), glutathione S transferase (GST), glutathione reductase (GSSG-Red) and quinone reductase. I-3-C produced decreased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. DHII produced increases in EROD, UDPGT, GST, GSSG-Red and quinone reductase, with decreases in NDMA-demethylase and GSH-Px activities. The only observed effect of THII was a modest induction of EROD activity. After treatment with the indole compounds for 10 days, I-3-C enhanced, while DHII diminished, CCl4-mediated 24-hr hepatotoxicity in rats. We conclude that DHII and THII are suitable candidates to develop further as potential chemoprotective and therapeutic agents for use in humans to treat disorders involving free radicals. THII has the greater radical scavenging efficacy, whereas DHII has the greater capacity to induce many different antioxidative enzymes. PMID- 1874468 TI - Sister chromatid exchange induced by 'pan masala' (a betel quid ingredient) in male mice in vivo. AB - Sister chromatid exchange (SCE) induced in vivo by 'pan masala', a betel quid ingredient, was studied in male mice. The mice were injected ip with an aqueous suspension of pan masala at doses of 5, 12.5, 25, 50, 100 or 200 mg pan masala/kg body weight. A significant dose-related increase in SCE was observed (Cochran Armitage trend test). The minimum effective dose was 25 mg/kg. The two highest doses caused significant delays in the cell cycle. These results indicate that pan masala is a potential DNA-damaging agent and cytotoxic to bone marrow cells. PMID- 1874469 TI - Tobacco-specific N-nitrosamines in tobacco and mainstream smoke of Indian cigarettes. AB - Different brands of Indian cigarettes were analysed, by gas chromatography thermal energy analysis, for the presence of carcinogenic tobacco-specific N nitrosamines (TSNA) in both tobacco and mainstream smoke. Preformed TSNA in cigarette tobacco ranged between 68 and 730 ng N-nitrosonornicotine (NNN)/cigarette, between 19 and 174 ng 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1 butanone (NNK)/cigarette and between 98 and 519 ng N-nitrosoanabasine (NAB) together with N-nitrosoanatabine (NAT)/cigarette. The amounts of NNN, NNK and NAB/NAT in mainstream smoke were 11-156, 7-73 and 17-146 ng/cigarette, respectively. PMID- 1874470 TI - Decreased incidence of diphenylamine-induced renal papillary necrosis in Syrian hamsters given dimethylsulphoxide. AB - The renal papillotoxicity of diphenylamine dissolved in dimethylsulphoxide (DMSO) was investigated in male Syrian hamsters, male Sprague-Dawley rats and female Mongolian gerbils. When diphenylamine in DMSO was administered orally to male Syrian hamsters (400, 600 or 800 mg/kg body weight/day for up to 9 days), the incidence of renal papillary necrosis was almost zero. Hamsters pretreated with DMSO (0.5 ml/100 g body weight/day) and 1 hr later given 400, 600 or 800 mg diphenylamine in peanut oil/kg body weight/day for 3 consecutive days had significantly reduced incidences of renal papillary necrosis (0/10, 0/10 and 1/10 in the low-, mid- and high-dose groups, respectively) when compared with hamsters given similar doses of diphenylamine but not pretreated with DMSO (5/10, 7/10 and 5/10 in the low-, mid- and high-dose groups, respectively). Focal, apex-limited renal papillary necrosis was observed in two Sprague-Dawley rats given 800 mg diphenylamine in DMSO/kg body weight/day orally for 9 days. Focal, intermediate renal papillary necrosis was observed in two additional rats administered 800 mg diphenylamine in DMSO/kg/day orally for 9 days. Renal papillary necrosis was not observed in any of the Mongolian gerbils. The results of these studies suggest that DMSO protects against diphenylamine-induced renal papillary necrosis in male Syrian hamsters. PMID- 1874471 TI - Concurrent bromosulphophthalein and antipyrine administration to assess liver blood flow and hepatic enzymes in rats. AB - This study investigated the feasibility of using concurrent iv administration of antipyrine (15 mg/kg body weight) and bromosulphophthalein (BSP; 25 mg/kg) in the rat. Antipyrine is used as an index of hepatic drug metabolism and BSP is used to assess hepatic blood flow. Plasma concentrations of BSP were described using biexponential phases, while antipyrine plasma concentrations were monoexponential. No significant difference was observed between antipyrine pharmacokinetic parameters in concurrent BSP rats when compared with controls. There was also no significant difference between BSP pharmacokinetic parameters in concurrent antipyrine rats when compared with controls, except in the alpha value (P less than 0.05). This indicates that BSP distribution may be affected by concurrent antipyrine administration. Therefore, simultaneous administration of both substrates is not acceptable to study hepatic blood flow. Another iv combination dose (25 mg BSP/kg body weight, followed by 15 mg antipyrine/kg 0.5 hr later) and a dose of 15 mg antipyrine/kg body weight only was administered to rats pretreated with phenobarbital (90 mg/kg body weight) for 6 days. Pharmacokinetic parameters of BSP, beta, k21, k23 and plasma clearance, in the pretreated rats were significantly different from non-pretreated rats. No significant difference was observed in the pharmacokinetic parameters of antipyrine between the combination dose and antipyrine dose in the phenobarbital pretreated rats. The half-lives of antipyrine in both pretreated groups decreased approximately by 70%, while the clearance increased four times compared with controls. The volume of distribution in these animals did not change as a result of phenobarbital pretreatment. This suggests that a 25 mg BSP/kg body weight dose followed by 15 mg antipyrine/kg 0.5 hr later may be a feasible approach to study liver blood flow, as well as hepatic efficiency in rats. PMID- 1874472 TI - Effect of androgen insensitivity on diabetogenesis in db/db male mice with testicular feminization (Tfm). AB - In C3H mice, a major component of susceptibility to the diabetogenic action of an obesity mutation (diabetes, db) is male gender associated. We tested whether increased male susceptibility was an androgen receptor mediated process. C3H.SW/Lt-derived db/db males were rendered androgen-receptor function-deficient by introducing the testicular feminization (Tfm) mutation of the X-linked androgen receptor gene. The db/db Tfm/Y males (phenotypically female in appearance) developed severe diabetes indistinguishable from that observed in standard db/db X + Y males. Castration of standard C3H.SW/Lt-db/db males (producing mutants with normal androgen receptors but reduced serum testosterone) also failed to block the gender-enhanced susceptibility. In contrast, female db/db littermates exhibited a milder hyperglycemia, and were more resistant to pancreatic beta cell necrosis and islet atrophy than any of the groups of db/db males. Although these data indicated that male-enhanced sensitivity to diabetogenic stress was independent of circulating androgens, the possibility that the gender dimorphism is predicated upon tissue ratios of active estrogens to androgens in glucose-producing tissues such as liver is discussed. PMID- 1874473 TI - Effects of estradiol and progesterone on rat uterine ribonuclease inhibitor activity. AB - The effects of estradiol (E2) and progesterone on rat uterine RNase inhibitor activity were investigated. RNase inhibitor activity was found to be most prominent in nuclear and cytosolic fractions of the uterus. Uterine RNase inhibitor activity in the 45,000 x g cytosolic fraction was stimulated by E2 over a 6-24 hr treatment period. Progesterone did not produce a significant change in the uterine cytosolic RNase inhibitor activity during the same period. PMID- 1874474 TI - Liposome-entrapped calcitonin and parathyroid hormone are orally effective in rats. AB - We have demonstrated that liposomally entrapped calcitonin (CT) and parathyroid hormone (PTH) can be orally effective in regulating blood calcium. Liposomal CT produced hypocalcemia and liposomal PTH produced hypercalcemia upon oral administration to rats. Specific liposomal formulations were necessary to affect the appropriate decrease and increase in blood calcium concentration. Future extension of these studies may lead to clinically valuable forms of liposomal peptide preparations. PMID- 1874475 TI - Insulin secretion in patients deficient in glucose-6-phosphate dehydrogenase. AB - Intravenous (IVGTT) and oral glucose tolerance tests (OGTT) were carried out in 12 men with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and in 11 normal men. The race, the mean age and body mass index were similar in the G-6-PD deficient and in the normal men. No significant differences were demonstrated between mean plasma glucose levels in the G-6-PD deficient subjects and those in the normal men during IVGTT and OGTT. In contrast the insulin levels were significantly lower for the G-6-PD deficient subjects as compared to the controls at 30 minutes (P less than 0.04) in the OGTT and at 1 min (P less than 0.001), 3 min (P less than 0.001), 5 min (P less than 0.001) and 10 minutes (P less than 0.002) in the IVGTT. All indexes of first phase insulin release were also significantly (P less than 0.001) lower in G-6-PD deficient men. These results emphasize the metabolic importance of G-6-PD in the process of glucose induced insulin release. PMID- 1874476 TI - Lipid and carbohydrate metabolism in premenopausal women given subdermal estradiol implants. AB - Fifteen premenopausal women were studied before and 6 weeks after receiving subcutaneous implants of 100 mg estradiol. Serum estradiol levels doubled; increases were also seen in fasting serum total cholesterol and in high-density lipoprotein cholesterol (HDL). This increase was confined to the HDL2 subfraction, and was not reflected in the HDL apolipoproteins. Low density lipoprotein (LDL) cholesterol levels were unchanged, as were those of apolipoprotein B, the major protein component of LDL. Carbohydrate metabolism was assessed in a subgroup of 12 women. Estrogen implantation reduced fasting plasma glucose levels but did not alter the plasma glucose response to an oral glucose tolerance test. Plasma insulin levels were unchanged both in the fasted state and during the glucose tolerance test. Our findings indicate that parenteral administration of estradiol can alter lipid and carbohydrate metabolism in premenopausal women. PMID- 1874477 TI - Cross sectional and longitudinal study of bone mineral content of the distal forearm in adult premenopausal women. AB - The range of fat corrected distal forearm mineral content (FMC) (at a site which comprises approximately 75% cortical and 25% trabecular bone) and the effect of aging on FMC were determined in normal premenopausal women. In 106 women (mean age 39; range 18-56) the mean FMC was 1.184 (SD 148) g/cm; fat correction increased this to 1.239 (SD 148) g/cm. There were significant correlations between fat corrected FMC and height, weight and BMI (r greater than 0.16; P less than 0.05). In 43 of these women (mean age 35; range 18-51) repeat measurements of FMC were performed. The last measurement was separated from the first by a mean time interval of 27 +/- 3 months. There was no significant change in uncorrected FMC (baseline 1.185 +/- 0.21 g/cm compared with their final measurement 1.182 +/- .020 g/cm; P = 0.51). Fat-corrected FMC (baseline 1.229 +/- .021 g/cm compared with 1.223 +/- .020 g/cm later) tended to decrease although this change was not significant (P = 0.06). Age ranked cusum analysis demonstrated a non-significant fat-corrected rate of change in FMC of -.3% yr in those over 35 years of age (P less than 0.10). This data suggests that if there is any distal forearm bone loss before the menopause it is negligible. PMID- 1874478 TI - Development of ligand-induced down-regulation and endocytosis of hepatic insulin receptors at weaning in the rat. PMID- 1874479 TI - Does interferon-beta therapy induce thyroid autoimmune phenomena? PMID- 1874480 TI - The effect of human amniotic fluid in supporting long-term survival of pancreatic islets in tissue culture. AB - Pancreatic islets obtained from newborn Lewis rats were kept free-floating in TCM 199 either in the presence of 50% human amniotic fluid (HAF), 50% Hank's balanced salt solution (HBSS) or 10% fetal calf serum (FCS) for up to 14 days. The culture, in the presence of HAF, resulted in a good islet viability as demonstrated by islet number, islet insulin content and insulin release into the medium. Contradictory results were obtained when HBSS was used as the medium supplement. Moreover, the islets cultured in HAF-supplemented medium are characterized by a marked replicatory activity as reflected by the incorporation of labeled thymidine into islet DNA and gradual increase in DNA content with the progression of culture time. Even if compared to DNA synthesis of islets cultured under so called standard culture conditions as e.g. supplementation of 10% FCS to the medium, 50% HAF but not yet 10% HAF was found to stimulate the islet replication twofold already after 4 days of culture. It was also demonstrated that FCS has no additional effect on HAF-stimulated DNA synthesis. These findings support the view that HAF-enriched culture medium may have a use in supporting the long-term survival of well preserved endocrine pancreatic tissue. PMID- 1874481 TI - Insulin prevents glucose induced inhibition of angiotensin II-stimulated aldosterone secretion. AB - In humans with diabetes mellitus or in individuals given infusions of insulin or insulin plus glucose, plasma aldosterone levels have been reported to be suppressed. Whether insulin has a direct effect to suppress aldosterone secretion by the adrenal gland has not been established. The effect of insulin on glucose induced inhibition of angiotensin II-stimulated aldosterone secretion was examined. The effect of glucose and insulin plus glucose on angiotensin II stimulated aldosterone secretion was examined in isolated perfused canine adrenal glands. In the absence of insulin, 15.6 mM glucose decreased angiotensin II stimulated aldosterone secretion by 35 +/- 7%, while in the presence of insulin the same glucose concentration had no significant effect on angiotensin II stimulated aldosterone secretion. In contrast, insulin had no effect on NaCl induced inhibition of angiotensin II-stimulated aldosterone secretion. Neither insulin alone nor saline vehicle affected angiotensin II-stimulated aldosterone secretion. These results (1) demonstrate that insulin can prevent inhibition of glucose-induced angiotensin II-stimulated aldosterone secretion, possibly by preventing a glucose-induced decrease in cell volume, and (2) suggest that the suppressed plasma level of aldosterone found in individuals with diabetes mellitus may in part be due to the direct effects of hyperglycemia on the adrenal gland secretion of aldosterone. PMID- 1874482 TI - Serum transferrin as a marker of bone growth in boys: correlation with serum alkaline phosphatase activity, plasma insulin-like growth factor 1 and rate of growth in height. AB - Transferrin (TF) has a growth promoting activity in cell culture. The aim of this work was to study possible relationships between serum TF, alkaline phosphatase activity (ALP), plasma insulin-like growth factor 1 (IGF-1) levels and rate of height increase in boys. 149 boys aged 13-15 yrs were studied. TF levels were measured using turbidimetric method. The serum levels of ALP could be used as a biochemical marker for bone formation. Significant correlation was found between serum TF levels and ALP levels (r = 0.31, P less than 0.0005). The TF levels are higher in iron-deficiency anemia. The hemoglobin (Hb) and serum ferritin were measured in all boys. Thirty-one of 149 boys had no iron-deficiency anemia (Hb 14.0 g/dl and serum ferritin 23 ng/ml). The rate of growth in height was estimated over a 5 month period. In these boys, the rate of growth in height was significantly correlated with serum TF levels (r = 0.37; P less than 0.05). A significant correlation was found between serum TF levels and plasma IGF-1 levels (r = 0.45; P less than 0.05). These data indicate that serum TF levels may be a marker of skeletal growth in normal boys. PMID- 1874483 TI - Antithyroid autoantibodies in the examined population with iodine prophylaxis after the Chernobyl catastrophe. AB - The aim of the present study was the observation of the frequency of antithyroid autoantibodies in the population in low endemic goitre area after mass iodine prophylaxis after the Chernobyl catastrophe and the estimation of TSH and thyroid hormones secretion in this population. On the basis of the investigations carried out we could conclude that the frequency of antithyroid autoantibodies in the population with confirmed endemic goitre is comparable to the frequency of antithyroid autoantibodies in the healthy population. ATA occurrence in children after iodine prophylaxis could confirm the hypothesis that thyroglobulin immunity is higher after iodine intake. The lower T3 concentration observed in the group with antithyroid autoantibodies suggests that autoantibodies may be involved in the thyroid hormones synthesis or peripheral conversion of thyroid hormones. PMID- 1874484 TI - Norepinephrine content in the brown adipose tissue of the developing obese Zucker rat. PMID- 1874485 TI - Half-disappearance time of endogenous GLP-1 immunoreactivity in man. PMID- 1874486 TI - 30th annual meeting of the European Society for Paediatric Endocrinology (ESPE). Berlin, August 25-28, 1991. Abstracts. PMID- 1874487 TI - Thymosin treatment of chronic hepatitis B: a placebo-controlled pilot trial. AB - Chronic hepatitis B is a severe and frequently progressive disease. We assessed the safety and efficacy of thymosin fraction 5 and thymosin-alpha 1 in a prospective, placebo-controlled trial in 12 patients with chronic hepatitis B. All patients had histological and biochemical evidence of active liver disease for at least 6 mo before treatment and were positive for serum hepatitis B virus DNA and HBsAg. Seven patients received thymosin fraction 5 or thymosin-alpha 1 and five patients received placebo twice weekly for 6 mo. By the conclusion of the study (1 yr), serum aminotransferase levels had improved significantly in thymosin-treated patients, but not in the placebo group. Six (86%) of the thymosin treated patients and one (20%) patient given placebo cleared hepatitis B virus DNA from serum (p less than 0.04, Fisher's exact test). After treatment, replicative forms of hepatitis B virus DNA were present in the liver specimens of four of five placebo-treated patients but in only one of seven thymosin-treated patients (p less than 0.04, Fisher's exact test). Response to thymosin therapy was associated with significant improvements in peripheral blood lymphocyte and CD3 and CD4 counts and in in vitro production of interferon-gamma over initial values. No significant side effects were observed in patients given thymosin or in placebo-treated patients. Clinical, biochemical and serological improvement in patients responding to thymosin were sustained during 26 +/- 3 mo of follow-up. The results of this pilot trial suggest that thymosin therapy promotes disease remission and cessation of hepatitis B virus replication in patients with chronic viral infection. PMID- 1874488 TI - Effect of insulin and plasma amino acid concentration on leucine metabolism in cirrhosis. AB - Clinically stable patients with cirrhosis demonstrate insulin resistance with regard to glucose metabolism. However, much less is known about the two major factors, insulin and plasma amino acid concentration, that regulate protein metabolism in cirrhotic patients. To examine this question, we performed paired euglycemic insulin clamp studies in combination with 14C-leucine and indirect calorimetry. In the first study insulin alone was infused, and the plasma amino acid concentration was allowed to decline. During the second study a balanced amino acid solution was infused with insulin to increase the total plasma amino acid concentration approximately twofold. Insulin-mediated glucose disposal (4.68 vs. 6.45 mg/kg-min, p less than 0.01) was significantly impaired by 30% in cirrhotic patients during both insulin clamp studies. In the postabsorptive state, cirrhotic patients manifested low plasma leucine (76 vs. 102 mumol/L) and alpha-ketoisocaproate (19 vs. 30 mumol/L) concentrations, but all parameters of leucine turnover were normal. When insulin alone was infused, the endogenous leucine flux (an index of protein degradation) declined similarly in cirrhotic patients (30.8 mumol/m2-min) and control (26.9) subjects, and this was accompanied by a similar decrease in plasma leucine concentration (31% vs. 33%). The decline in circulating leucine concentration was accompanied by a parallel decline in leucine oxidation (5.1 vs. 4.6 mumol/m2-min) and nonoxidative (28.9 vs. 26.0 mumol/m2-min) leucine disposal, which were of similar magnitude in cirrhotic patients and control subjects, respectively. In both cirrhotic patients and control subjects, combined hyperinsulinemia/hyperaminoacidemia elicited a similar stimulation of nonoxidative leucine disposal (an index of protein synthesis) and leucine oxidation while causing a greater suppression of endogenous leucine flux than observed with insulin alone. Thus the suppressive effect of insulin on protein degradation and the stimulatory effect of insulin/amino acid infusion on protein synthesis are not impaired in cirrhotic patients, demonstrating a clear-cut dissociation between the effects of insulin on protein and glucose metabolism. PMID- 1874489 TI - Quantitative evaluation of parenchymal liver cell volume and total hepatocyte number in cirrhotic patients. AB - A simple morphometrical method was developed using a color image analyzing system, which allowed quantitative evaluation of parenchymal liver cell volume and total hepatocyte number in cirrhotic patients. With this method, we estimated these values in 29 cirrhotic patients who underwent hepatic resection (nine cases) or nonshunting operation (20 cases). Liver volume, calculated from computed tomographic images, was 976 +/- 196 cm3 (range = 602 to 1,376 cm3); the parenchymal cell volume ratio, obtained based on liver histological appearance with silver stain, was 0.665 +/- 0.092 (range = 0.510 to 0.881); and the parenchymal cell volume, calculated by multiplying the liver volume with the parenchymal cell volume ratio, was 645 +/- 140 cm3 (range = 403 to 936 cm3). The total hepatocyte number obtained in a similar manner using hematoxylin-stained specimens was 1.72 +/- 0.56 x 10(11) (range = 0.74 to 2.94 x 10(11)). The validity and applicability of the method is discussed, and the data are compared with those reported in other studies. PMID- 1874490 TI - The lack of relationship between hepatotoxicity and lithocholic-acid sulfation in biliary bile acids during chenodiol therapy in the National Cooperative Gallstone Study. AB - To test whether hepatotoxicity occurring in National Cooperative Gallstone Study patients was caused by a toxic effect of chenodiol per se or of lithocholate caused by defective sulfation, bile samples were analyzed using a new high performance liquid chromatography method that measures the proportions of the four individual lithocholate amidates (sulfated and unsulfated lithocholylglycine and lithocholyltaurine) and all common bile acid amidates. Samples were obtained from National Cooperative Gallstone Study patients (n = 17) with abnormal light microscopic liver biopsy results or major aminotransferase elevations and from a matched control group of patients (n = 14) who received similar chenodiol doses but had no evidence of liver injury. Bile samples from 45 healthy subjects were also analyzed. The analytical method was validated by showing that the percentage of chenodiol and cholic and deoxycholic acid obtained by high-performance liquid chromatography correlated highly (r greater than 0.94) with previous gas-liquid chromatography analyses of these samples by the National Cooperative Gallstone Study Reference Laboratory. No significant differences were seen between gallstone patients with and without evidence of liver injury for percent total lithocholate amidates, percent sulfated or unsulfated lithocholate amidates or percent chenodiol amidates. Lithocholate was partially sulfated in all bile samples (52% +/- 17% [mean +/- S.D., n = 50]), but the extent of sulfation varied widely between and within patients during the course of therapy. Mean values of healthy subjects were similar and also showed a wide range in the extent of lithocholate sulfation. It is concluded that (a) liver injury caused by these doses of chenodiol could not be attributed to the accumulation of unsulfated lithocholate per se in circulating bile acids; (b) liver injury appeared to be, directly or indirectly, caused by enrichment in circulating bile acids with chenodiol or chenodiol together with lithocholate, suggesting that the hepatocytes of those patients with hepatotoxicity were injured by the change induced in bile-acid metabolism by the feeding of chenodiol; and (c) about half of lithocholate amidates in bile samples were sulfated, but the extent of sulfation was highly variable both in gallstone patients and healthy subjects. PMID- 1874491 TI - Are patients with primary biliary cirrhosis hypermetabolic? A comparison between patients before and after liver transplantation and controls. AB - Wasting is common in end-stage primary biliary cirrhosis and causes concern in patients facing liver transplantation. We have quantified resting metabolic rate and diet-induced thermogenesis in seven patients with primary biliary cirrhosis, in seven patients after liver transplantation who had previously been diagnosed as having primary biliary cirrhosis and in seven controls. Resting metabolic rate was elevated in the primary biliary cirrhosis group (4.44 +/- 0.81 kJ/hr/kg body wt; mean +/- S.D.) compared with the post-liver-transplantation group (3.39 +/- 0.40 kJ/hr/kg body wt) (p less than 0.005) and compared with control subjects (3.65 +/- 0.23 kJ/hr/kg body wt) (p less than 0.01). A highly significant relationship was found between the severity of liver disease in the primary biliary cirrhosis group, as assessed by Child-Pugh score, and the resting metabolic rate group (r = 0.93; p less than 0.005). After a liquid meal (41 kJ/kg body wt), the metabolic rate increased, with similar peak changes from baseline occurring in all three groups. However, the rise persisted significantly longer in the primary biliary cirrhosis patients, and thus the integrated mean postprandial energy expenditure over the 4-hr postprandial observation period was greater in the primary biliary cirrhosis group than in the other two groups (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874492 TI - Sexual function and testosterone levels in men with nonalcoholic liver disease. AB - The effects of nonalcoholic liver disease on sexual desire, arousal, activity, orgasmic function and satisfaction and serum testosterone levels were studied in 75 men with nonalcoholic liver disease. Each man was interviewed about his sexual behavior and problems and was asked to comment on whether he felt liver disease affected his sexual function. The average age of the patients was 49 yr, and a wide variety of liver diseases was represented. Child-Pugh grading was A in 51 patients, B in 18 and C in 6; the mean duration of liver disease was 8 yr. Sexual desire, arousal and activity of patients with grade A disease were within the ranges observed in studies of healthy men of comparable age. Diminished sexual desire was reported by 2% of grade A patients and 35% of grade B and C patients (p less than 0.005). Arousal problems were noted by 16% of grade A patients, 60% of grade B patients and 67% of C patients (p less than 0.005). Loss of erection and inability to regain erection were noted by 7%, 40% and 67% of grade A, B and C patients, respectively (p less than 0.01). Premature and retarded ejaculation were more frequent in patients classed in Child-Pugh grades B and C. Frequency of coitus and orgasm were significantly higher in grade A patients than in grade B and C patients. Total and free testosterone levels were (in nanograms per milliliter) A, 677/1.78; B, 416/1.06; and C, 178/0.43 (p less than 0.002). We concluded that Child-Pugh grade A nonalcoholic liver disease in men does not affect sexual desire, function or performance. Men with disease grades B and C have significant sexual dysfunction and significant reduction of both total and free testosterone levels. PMID- 1874493 TI - Systemic, splanchnic and renal hemodynamic effects of a dopaminergic dose of dopamine in patients with cirrhosis. AB - The effects of dopamine on kidney function have not been elucidated in patients with cirrhosis. Moreover, although increased portal pressure has been observed with supradopaminergic doses of dopamine in these patients, the splanchnic hemodynamic effects of low doses of dopamine have not been previously studied. Thus we studied the acute systemic, splanchnic and renal hemodynamic effects of a dopaminergic dose of dopamine (1.5 micrograms/kg body wt min) in nine cirrhotic patients. Plasma dopamine levels increased markedly from 35 +/- 20 pg/ml to 31,400 +/- 4,900 pg/ml during dopamine administration. A significant diastolic pressure decrease of 10% was associated with a 15% increase in heart rate. Cardiac output was not altered. Although dopamine significantly increased azygos blood flow by 16%, wedged and free hepatic venous pressures were not altered. Dopamine significantly increased renal blood flow by 31%, but did not change the glomerular filtration rate. We conclude that a dopaminergic dose of dopamine increases azygos blood flow but not the hepatic venous pressure gradient. Finally, although it increases renal blood flow, dopamine does not seem to have any beneficial effects on glomerular filtration rate in cirrhotic patients. PMID- 1874494 TI - Natural killer activity of human liver-derived lymphocytes in various liver diseases. AB - Liver-derived lymphocytes were isolated from 40 human livers with end-stage liver disease that were removed at the time of orthotopic liver transplantation. In addition, 10 resection specimens or whole livers removed from patients with liver cancer and seven normal livers (unused donor organs) were studied as controls. Liver-derived lymphocytes were isolated from enzymatically digested tissue by gradient centrifugation and adherence to plastic. Their phenotypical characteristics were studied by two-color flow cytometry, and effector cell function was determined in 4-hr 51Cr-release assays against a natural killer sensitive target, K562 (natural killer activity), natural killer-resistant Daudi line (lymphokine-activated killer activity) and by P815 line with or without phytohemagglutinin to assess lectin-dependent cellular cytotoxicity. Liver derived lymphocytes isolated from normal liver contained equal proportions of T and natural killer lymphocytes (mean natural killer/T ratio = 0.7). CD3-CD56+CD16 natural killer cells were the main natural killer subset present in liver derived lymphocytes, in contrast to the predominant natural killer phenotype in the circulation (CD56+CD16+). Control liver-derived lymphocytes had levels of cytotoxicity significantly greater than those of the normal peripheral-blood lymphocytes against all three targets. In contrast, liver-derived lymphocytes isolated from organs with advanced liver disease differed markedly in the natural killer/T cell ratio and levels of liver-derived lymphocyte cytotoxicity. Liver derived lymphocytes obtained from hepatocellular carcinoma or rejecting allografts treated by immunosuppressive therapy had virtually no cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874495 TI - Accurate prediction of death by serial determination of galactose elimination capacity in primary biliary cirrhosis: a comparison with the Mayo model. AB - We retrospectively analyzed the predictive accuracy of serial determinations of galactose elimination capacity in 61 patients with primary biliary cirrhosis. Death was predicted from the time that the regression line describing the decline in galactose elimination capacity vs. time intersected a value of 4 mg.min-1.kg 1. Thirty-one patients exhibited decreasing galactose elimination capacity; in 11 patients it remained stable and in 19 patients only one value was available. Among those patients with decreasing galactose elimination capacity, 10 died and three underwent liver transplantation; prediction of death was accurate to 7 +/- 19 mo. This criterion incorrectly predicted death in two patients with portal vein thrombosis; otherwise, it did better than or as well as the Mayo clinic score. The latter was also tested on our patients and was found to adequately describe risk in yet another independent population of patients with primary biliary cirrhosis. Cox regression analysis selected only bilirubin and galactose elimination capacity, however, as independent predictors of death. We submit that serial determination of galactose elimination capacity in patients with primary biliary cirrhosis may be a useful adjunct to optimize the timing of liver transplantation and to evaluate new pharmacological treatment modalities of this disease. PMID- 1874496 TI - Sodium retention and hepatic function after two-thirds hepatectomy in the rat. AB - Recently it was suggested that the onset of sodium retention in experimental cirrhosis in rats is related to a critical threshold of hepatic function, as assessed by the aminopyrine breath test. The aim of this study was to evaluate whether sodium retention occurred after two-thirds hepatectomy in rats and to investigate the relationship between sodium retention and changes in hepatic function associated with liver regeneration in this model. Sodium balance, creatinine clearance, serum sodium and the aminopyrine rate constant of elimination were evaluated daily for 4 days after surgery in partially hepatectomized (n = 6) and sham-operated rats (n = 6). All rats in the partial hepatectomy group exhibited sodium retention (sodium balance greater than 0.7 mmol/day) 24 hr after surgery. This was associated with a 62% reduction of the aminopyrine rate constant of elimination. Spontaneous natriuresis which occurred between 2 and 4 days after surgery, was associated with an increase in the aminopyrine rate constant of elimination (from 0.73 +/- 0.02 x 10(-2) min-1 on the last day of sodium retention to 0.95 +/- 0.04 x 10(-2) min-1 on the first day of natriuresis [p less than 0.05]). In contrast, no change in creatinine clearance occurred over the same period. A negative curvilinear association was found between sodium balance and the aminopyrine rate constant of elimination in all animals (r = -0.72, p less than 0.001). These observations indicate that natriuresis is related to the recovery of liver function, not to changes in creatinine clearance. In conclusion, the concept of a critical threshold of liver function below which sodium retention occurs has been substantiated in this model of hepatic dysfunction. PMID- 1874497 TI - Effect of cyclosporine and steroids on canine bile flow. AB - Cyclosporine and hydrocortisone are the main immunosuppressants used in transplant surgery. The purpose of this study was to determine the effect of intravenous administration of cyclosporine and hydrocortisone on bile flow in dogs. Cyclosporine in doses of 0.5, 1.0 and 1.5 mg.kg-1.hr-1 were administered along with 18 mumol/min intravenous sodium taurocholate to dogs with chronic biliary and gastric fistulas. Bile volume and bile chloride concentration and output were increased by cyclosporine in a dose-related manner, whereas bile salt concentration decreased and bile salt output was unchanged. Hydrocortisone produced small but significant increases in bile flow only at the highest dose of hydrocortisone administered. Subsequently, experiments were performed when sodium taurocholate was administered in progressively increasing doses (9, 18 and 36 mumol/min), with the dose changed every hour. Bile volume, [14C]erythritol clearance in bile and bile salt concentrations were measured with and without cyclosporine and hydrocortisone administration. Cyclosporine increased the bile salt-independent fraction of canalicular bile flow and ductular bile flow. Experiments evaluating the role of the cyclosporine carrier polyoxyethylated castor oil (Cremophor EL) demonstrated that this substance had no independent choleretic activity, whereas cyclosporine dissolved in ethanol and administered without Cremophor EL significantly increased bile flow. The results of this study indicate that cyclosporine stimulates chloride-rich choleresis independent of bile salt secretion. PMID- 1874498 TI - Inhibition of glutathione synthesis in the liver leads to S-adenosyl-L-methionine synthetase reduction. AB - The hepatic levels of glutathione in rats treated with buthionine sulfoximine (4 mmol/kg), an inhibitor of glutathione synthesis, were 72.5% +/- 4.9% of those determined in control animals. This decrease in glutathione concentration was prevented by the administration of glutathione monoethyl ester (7.5 mmol/kg). S Adenosyl-L-methionine-synthetase activity in the liver of rats treated with buthionine sulfoximine was 39.4% +/- 6.5% of that determined in control animals. Again, glutathione monoethyl ester prevented the effect of buthionine sulfoximine on S-adenosyl-L-methionine-synthetase activity. There was a close correlation (r = 0.936) between the hepatic levels of glutathione and S-adenosyl-L-methionine synthetase activity. The hepatic concentration of S-adenosyl-L-methionine in buthionine sulfoximine-treated animals was 59.7% +/- 3.7% of that measured in control rats. Contrasting with the protective effects mentioned above, glutathione monoester had no preventive action on buthionine sulfoximine-induced S-adenosyl-L-methionine depletion. Electron microscopic examination of liver samples of rats after buthionine sulfoximine administration showed evidence of liver degeneration, which was attenuated by glutathione monoethyl ester treatment. Glutathione (7.5 mmol/kg) treatment was less effective than glutathione monoethyl ester in attenuating buthionine sulfoximine effects on hepatic S-adenosyl-L-methionine metabolism and morphology. The reduction of S adenosyl-L-methionine-synthetase activity observed after treatment with buthionine sulfoximine and its prevention by glutathione monoethyl ester, as well as the correlation between the activity of this enzyme and glutathione levels, indicate that glutathione plays an important role in maintaining S-adenosyl-L methionine-synthetase activity in the liver. PMID- 1874499 TI - Vanadate inhibits glucose output from isolated perfused rat liver. AB - Previous studies have demonstrated that vanadate ions mimic many of the actions of insulin in in vitro systems. Also, vanadate administered to diabetic hyperglycemic rats lowers their blood glucose levels to normal values. In this study we demonstrate that vanadate inhibits glucose output in the isolated perfused rat liver. Glucose production was suppressed maximally (about 50% to 60%), on addition of extremely low vanadate ion concentrations (0.5 to 1 mumol/L). This concentration is about two log units lower than the vanadate ion concentrations that are required to activate hexose uptake and glucose metabolism in vitro and is within the range of endogenous intracellular vanadium concentration. Insulin had little or no effect in inhibiting hepatic glucose output in this experimental system. The effect of vanadate ions is rapid in onset and is not accompanied by any signs of liver toxicity as assessed by various criteria. In conclusion, the study indicates that (a) vanadate ions inhibits hepatic glucose output, maximally and at extremely low, nontoxic concentrations (ID50 = 0.7 +/- 0.1 mumol/L). (b) The modulation action of the ion is fast and probably occurs at point(s) distal to the insulin receptor itself. (c) The liver participates in the process of maintaining euglycemia in diabetic rats receiving optimal doses of vanadate orally. PMID- 1874500 TI - Mechanisms and regulation of bile secretion. PMID- 1874501 TI - Treatment of chronic hepatitis B. PMID- 1874502 TI - Split-liver transplantation: one plus one doesn't always equal two. PMID- 1874503 TI - Is intrapulmonary arteriovenous shunting and hypoxemia a contraindication for liver transplantation? PMID- 1874504 TI - CEOs outline changes in collaboration. PMID- 1874505 TI - Annual survey: incentive plans on the rise in hospitals. AB - Long a fixture in other fields, incentive plans are becoming much more common- and are being received more favorably--in the health care sector. Hospitals are implementing incentive compensation plans at an explosive rate, according to the 1991 Hay Hospital Management/Professional Survey of compensation and benefits data from over 1,200 U.S. hospitals. The survey also looks at compensation's link to organizational performance and gives a list of average base salaries and total cash compensation for a number of health care positions. Learn the latest trends, exclusively in Hospitals. PMID- 1874506 TI - Outpatient bundling regulation would be costly for hospitals. AB - A new federal outpatient bundling regulation could plunge hospitals into a costly billing and administrative nightmare. Among its provisions, hospitals would be required to bill Medicare for diagnostic procedures or tests provided to outpatients by outside suppliers--even if provided outside hospitals' outpatient departments. PMID- 1874507 TI - Foster McGaw winner: size no barrier to this hospital's outreach. AB - Franklin (NH) Regional Hospital is a tiny rural provider with a huge commitment to its community. In the past five years, the 49-bed hospital has pumped nearly $1 million into social and educational programs. The ambitious outreach effort is a key reason why Franklin recently won the Foster G. McGaw Prize, presented by the Baxter Foundation, Deerfield, IL, and the AHA. PMID- 1874508 TI - Exploring options in patient entertainment. PMID- 1874509 TI - Suppliers tackle hospital labor shortage. PMID- 1874510 TI - Bond insurance flood unlikely to abate soon. PMID- 1874511 TI - Outpatient clinic payment plan poses challenges. PMID- 1874512 TI - Preventing board conflict over mission, margin. PMID- 1874513 TI - Two hospitals share data services, save millions. PMID- 1874514 TI - Hospitals must regain the public's trust. PMID- 1874515 TI - Aglycosylated chimeric mouse/human IgG1 antibody retains some effector function. AB - The N-linked carbohydrate attachment site of human IgG1 Ab has been eliminated by site-directed mutagenesis. Effector functions of aglycosylated Ab was then compared to its native counterpart. Aglycosylated Ab failed to exhibit any ADCC activity, but a significant level of CDC activity was retained by the aglycosylated Ab. These observations differ from those reported previously. Serum half-life and biodistribution of aglycosylated Ab in mice were comparable to the native Ab. Together, these results show that some, but not all, effector functions of a human IgG1 Ab are affected by aglycosylation. PMID- 1874516 TI - In vitro immunization of human tonsilar lymphocytes: effects of PWM and rIL-6. AB - We previously described a system for the in vitro immunization of human tonsilar lymphocytes under serum-free conditions in the presence of muramyl dipeptide and rIL-2 (1). Further studies with this system reveal possible roles for PWM and rIL 6 in the immunization process. The addition of these factors led to an increase in the levels of antibody produced in lymphocyte cultures. The time of addition of these factors was found to be important in determining the extent of their effects on the overall yields of antigen-reactive cells. PMID- 1874517 TI - Characterization and heterogeneity of monoclonal antibodies directed to intestinal mucin derived from Crohn's disease small bowel. AB - A panel of 12 monoclonal antibodies were produced by immunization of Balb/c mice with small bowel epithelial cells obtained from a patient with active well documented Crohn's disease. The clones were derived by screening with immunofluorescence microscopy; those with staining patterns suggestive of mucin directed epitopes were chosen for study. Several distinct patterns of staining reactivity were noted, including reagents with homogeneous, luminal, heterogeneous and peripheral goblet cell activity. In addition, SDS polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis revealed reactivity to high molecular weight mucin. The reactive antigen was resistant to proteinase digestion. No endoneuraminidase activity was detected; however, one neuraminidase sensitive sialic acid epitope was demonstrated. Confirmation of glycoprotein epitopes was accomplished by testing purified mucins from several areas of the gastrointestinal tract by ELISA. Finally, individual small bowel goblet cell heterogeneity was demonstrated by immunofluorescence, Western blotting, and antibody affinity chromatography. These data demonstrate both by morphology and specific binding of antibody affinity chromatography a significant degree of small bowel goblet cell mucin heterogeneity. PMID- 1874518 TI - Characterization of Pgp-1 antigen on murine B lymphocytes using a new anti-Pgp-1 monoclonal antibody. PMID- 1874519 TI - Use of sulfonation method to determine DNA contamination of cell cultured monoclonal antibodies produced for human therapeutics. AB - In the past few years, culture of transformed mammalian cells has been widely used to produce natural or recombinant molecules, as monoclonal antibodies (MAb) and cytokines. For therapeutic use, the cellular DNA level must be determined. A number of techniques have been developed to measure the DNA content, based on sequential extraction blotting and hybridization with a labeled DNA probe. The sulphonate marker has been recently introduced by PBS-Orgenics; it allows the determination of picograms (pg) quantities of purified DNA. However, it is not simple to measure in complex biological samples especially when a large amount of protein is present. In considering the following points: 1. Precautions in handling the samples at different steps of preparation; 2. Modifications of the original technique 3. Concentration of samples expected at very low level, we are able to dose up to 2 pg of contaminant DNA per mg of MAb with a satisfactory reproducibility and reliability. This level is required not only to qualify final MAb but also to evaluate the efficiency of the purification process. Efforts are being made to achieve a better sensitivity. PMID- 1874520 TI - Impedance cardiography using band and regional electrodes in supine, sitting, and during exercise. AB - The electrical impedance and its first derivative (dZ/dt) were measured at 100 kHz on 10 normal males in supine, sitting, and during upright bicycle exercise in order to compare the contribution of regional electrodes to the standard band electrode signal and to evaluate the possible use of spot electrodes for stroke volume (SV) measurements. Simultaneous measurements were made from band electrodes placed around the neck and lower thorax and from spot electrodes which recorded signals from the neck, upper thorax, and lower thorax. The results showed that approximately equal parts of the dZ/dt waveform came from the neck and upper thorax with the lower thorax contribution small but providing important features of the band signal. Changing from supine to sitting showed percentage decreases of 35% and 46% for the band and neck signals, respectively, with an increase of 19% for the upper thorax signal. The percentage increases in SV with upright exercise were 34%, 52%, and 24% for the bands, neck, and upper thorax signals, respectively. Band signal is made up of different signals from various regions of the thorax. Its ability to predict correct changes in SV may result from some "lucky" coincidences. The use of regional electrodes will probably not give the same SV information but may be important in measuring regional activities of the central circulation. PMID- 1874521 TI - In vitro measurement and characterization of current density profiles produced by non-recessed, simple recessed, and radially varying recessed stimulating electrodes. AB - Potential fields induced by nonrecessed, simple recessed, and radially varying recessed electrode designs were measured in vitro. Comparison of experimental results with theoretical analyses substantiated the experimental measurement technique and emphasized the importance of considering both nonuniform charge injection and surface electrochemistry when designing implantable stimulating electrodes. Radially varying recesses produced uniform charge injection at the electrode surface and at the aperture-tissue interface. In general, the radially varying recessed electrodes provided a combination of uniform charge injection and flexibility in design and fabrication that warrants their incorporation into all appropriate planar stimulating electrode designs. PMID- 1874522 TI - The potential distribution generated by surface electrodes in inhomogeneous volume conductors of arbitrary shape. AB - The use of the boundary element technique in the computation of the potential distribution within isotropic inhomogeneous volume conductors of arbitrary shape set up by current injected through surface electrodes is presented. The derived algorithm is validated by comparing its solution to analytical solutions in the case of a concentric bipolar electrode configuration on a homogeneous, spherical volume conductor. This problem is essentially a mixed boundary value problem. It is shown that approximations by treating this problem as a Neumann problem, which have recently appeared in the literature, are valid for remote field points only. Applications to the modeling of the field of cardiac defibrillation electrodes are presented. PMID- 1874523 TI - Prediction of magnetically induced electric fields in biological tissue. AB - There are many potential medical applications in which it is desirable to noninvasively induce electric fields. One such application that serves as the backdrop of this work is that of stimulating neurons in the brain. The magnetic fields necessary must be quite high in magnitude, and fluctuate rapidly in time to induce the internal electric fields necessary for stimulation. Attention is focused on the calculation of the induced electric fields commensurate with rapidly changing magnetic fields in biological tissue. The problem is not a true eddy current problem in that the magnetic fields induced do not influence the source fields. Two techniques are introduced for numerically predicting the fields, each employing a different gauge for the potentials used to represent the electric field. The first method employs a current vector potential (analogous to A in classical magnetic field theory where DEL x A = B) and is best suited to two dimensional (2-D) models. The second represents the electric field as the sum of a vector plus the gradient of a scalar field; because the vector can be determined quickly using Biot Savart (which for circular coils degenerates to an efficient evaluation employing elliptic integrals), the numerical model is a scalar problem even in the most complicated three dimensional geometry. These two models are solved for the case of a circular current carrying coil near a conducting body with sharp corners. PMID- 1874524 TI - Finite-difference time-domain calculations of absorbed power in the ankle for 10 100 MHz plane wave exposure. AB - This paper presents finite-difference time-domain (FDTD) calculations of the short-circuit current and the specific energy absorption rate (SAR) in the ankle. Plane wave exposures from 10 to 100 MHz for an adult, a 10-year old and 5-year old are considered. The calculations are performed in two parts. Firstly, the coupling between a homogeneous whole body phantom and the applied field is calculated. The region around a lower leg is then expanded, the leg being described by a realistic fine-scale, heterogeneous model. Tangential electric field components from the first part are used as boundary conditions on the reduced domain of the second part. Electric field values based on a maximum SAR of 20 W . kg-1 are presented. PMID- 1874525 TI - Recursive parameter identification of constrained systems: an application to electrically stimulated muscle. AB - In the application of real-time identification methods for diagnosis or adaptive control of biomedical systems, there is often known model information that is ignored. Constraints on the allowable values of parameters, which may be based on physical considerations, are often neglected because the information does "fit" easily into commonly used parameter-identification algorithms. In this paper a method of incorporating constraints on model parameters is developed. This method is applicable to most recursive parameter-identification algorithms. It enforces linear equality constraints on identified parameters. The use of this method for the real-time identification of autoregressive moving-average-type time series models, subject to parameter constraints, is described in detail. These constraints may be time varying. At each time step, the parameter estimate obtained by a recursive least squares estimator is orthogonally projected onto the constraint surface. This simple idea, when appropriately executed, enhances the output prediction accuracy of estimated parameters. Using constraint information in this way is important when we do not wish to destroy a "natural" parameterization of the model (by an initial projection to incorporate equality constraints), or when we cannot use a single initial model simplification (because the constraints are time varying or involve inputs and outputs). Because it improves output prediction at future times, this method is advantageous for use in predictive adaptive controllers. The use of this algorithm is demonstrated in the identification of electrically stimulated quadriceps muscles in paraplegic human subjects, using percutaneous intramuscular electrodes. The nonlinear steady state force versus pulsewidth recruitment characteristic of the electrode-muscle system is identified simultaneously with the input-output muscle response dynamics, using a Hammerstein-type model. Knowledge of the recruitment curve's shape is translated into constraints on the identified parameters. This information improves the experimental predictive quality of the identified model. PMID- 1874526 TI - A method for evaluating the selectivity of electrodes implanted for nerve simulation. AB - The scale of stimulating electrodes possible for use in functional electrical stimulation to restore motor and sensory function is rapidly approaching that of individual neurons. Although the electrodes may approach the dimensions of single nerve cells, it is unclear if the region of excitation elicited by each electrode will be correspondingly small. Previous techniques for evaluating this have either been tedious or have lacked the resolution necessary. This paper describes a method that uses the refractory interaction of the compound action potentials elicited by a stimulus pulse pair, along with high-resolution recording of those potentials, to achieve measurements of the selectivity of stimulation down to the scale of a few axon diameters. The feasibility of this technique is demonstrated in sciatic nerves of frogs (Rana Catesbiana) acutely implanted with a sapphire electrode array. PMID- 1874527 TI - Air cooling for an interstitial microwave hyperthermia antenna: theory and experiment. AB - Microwave antennas are inserted through brachytherapy catheters implanted in a tumor to deliver interstitial hyperthermia cancer therapy. Theoretical calculations show that a cooling rate on the order of 0.1 W/cm length of catheter will significantly improve the radial uniformity of the temperature distribution of single antennas or arrays. Experiments and theoretical calculations show that air passing through the annulus between the antenna and the catheter at 10 L/min or less will produce such a cooling rate in a 2.2-mm OD catheter that has both ends accessible. To maintain uniformity of cooling rate along the catheter, it is better to control the cooling rate by preheating the air entering the catheter to 30-40 degrees C than it is to control the flow rate of room-temperature air. Ohmic heating of the antenna feedline does not confound the air cooling action significantly. PMID- 1874528 TI - A blind mobility aid modeled after echolocation of bats. AB - A new model of a mobility aid for the blind was designed using microprocessor and ultrasonic devices. This mobility aid was evaluated based on psychophysical experiments. In this model, a downswept FM ultrasound signal is emitted from a transmitting array with broad directional characteristics in order to detect obstacles. The ultrasound reflections from the obstacles are picked up by a two channel receiver. The frequency of the emitted ultrasound is swept from 70 to 40 kHz within 1 ms, so it has almost the same characteristics as the ultrasound a bat produces for echolocation. The frequency of the reflected ultrasound wave is down converted by about 50:1 by using a microcomputer with A/D and D/A converters. These audible waves are then presented binaurally through earphones. In this method obstacles may be perceived as localized sound images corresponding to the direction and the size of the obstacles. From the results of psychophysical experiments, it was found that downswept FM ultrasound was superior for the recognition of small obstacles compared to other ultrasonic schemes. With it a blind person can recognize a 1-mm-diameter wire. It was also proved that the blind could discriminate between several obstacles at the same time without any virtual images. This mobility aid, modeled after the bat's echolocation system, is very effective at detecting small obstacles placed in front of the head. PMID- 1874529 TI - Magnetic search coil system for linear detection of three-dimensional angular movements. AB - The design of a two-dimensional (2D) magnetic field search coil system based on the phase detection principle is described. The system was developed to record horizontal and vertical eye and head movements of small, unrestrained laboratory animals. It is also applicable for measuring three-dimensional (3D) eye and head movements in primates and man. The output is linear over 355 degrees in the horizontal plane and over +/- 60 degrees in the vertical direction. The procedure of recording 3D eye and head movements is discussed. PMID- 1874530 TI - Design and validation of the transparent oxygen sensor array. AB - A new oxygen monitoring system has been developed that consists of an array of transparent, independently-connected oxygen sensors mounted on a glass plate. This system is intended for continuous monitoring of oxygen at multiple locations on the surface of exteriorized tissues, while simultaneously visualizing microvascular activity. The sensor array is fabricated by techniques similar to those employed for semiconductors, which facilitate customization of sensor size and pattern to best monitor oxygen in a given physiologic preparation. Methods are described for characterizing the performance of the sensor array in vitro, including studies on the oxygen sensitivity, stability of the signal, and detection of oxygen gradients. An example of in vivo application of the sensor array is also presented. PMID- 1874531 TI - Reconstruction of sequential cardiac in-plane displacement patterns on the chest wall by laser speckle interferometry. AB - Time-average speckle interferometry has been applied to obtain displacement patterns on the chest wall produced by cardiac action, in the absence of breathing, during various phases of the cardiac cycle. This has been achieved by an electronic shutter, controlled by the electrocardiogram of the subject. The recorded holographic plates processed under identical conditions are scanned by the pointwise method to obtain the absolute displacements at various locations corresponding to the activities of the various cardiac chambers and values. These data are transformed to a 40 x 30 matrix by an interpolation method and, from this, three-dimensional displacement plots are reconstructed by an IBM PC/AT computer. These patterns shown the displacements over the entire cardiac area corresponding to the activities of various regions during the cardiac cycle. The apex and aortic valve areas show the maximum displacements during the systolic phase. During the diastolic phase the activities over the low pressure atrial regions are also observed. The results obtained outline the functional details of the normal heart and the activities over various areas are in agreement with that of other noncontact techniques. PMID- 1874532 TI - A fast and simple algorithm for the calculation of convective heat transfer by large vessels in three-dimensional inhomogeneous tissues. AB - A fast and simple algorithm has been presented for the calculation of time dependent temperature distributions in inhomogeneous vascularized tissue. Three dimensional anatomical data of tissues and vessel structures are decomposed into elementary cubic nodes by a special digitizing routine with vessels represented by connected strings of vessel nodes. Vessel cross sections may be irregular shaped and/or tapered. Conductive and convective heat transfer was calculated through use of the heat balance technique on each cubic node resulting in an explicit finite difference computational scheme. Employing a three time level scheme, the Fourier stability criterion is circumvented allowing arbitrary time steps to be defined in the algorithm. Time steps as large as 100 times the Fourier restricted one still result in stable and convergent calculations of the stationary temperature distribution. Vessels with different flows and diameters are incorporated by performing a vessel specific second discretization step in time. Using the new algorithm as a mathematical tool the thermal equilibration length of vessel segments have been established under a broad range of geometrical and flow conditions. Validation followed from comparing transient and stationary temperature distributions derived by the proposed algorithm to those from an accurate cylindrical numerical model. Predicted values for the thermal equilibration lengths are compared to an analytical expression and phantom experiments. The algorithm is incorporated in a thermal model being the main part of our hyperthermia treatment planning system. PMID- 1874533 TI - A pseudomatched filter model applied to the transient system of human vision. AB - A pseudomatched filter configuration is presented as a model for the transient system of the human visual perception. This model has resemblances to the Reichardt [1] and the Rashbass [2] model, but on the other hand the pseudomatched filter model is linear. The choice of the model is based on the shape of the psychophysically measured impulse response and on physiological and functional arguments. The parameters of the model are estimated for different data sets. The behavior of the model agrees with the experimental data in all essential aspects, and can be used for prediction and further modeling of the human visual system. PMID- 1874534 TI - Influence of thyroidectomy on seminal vesicular glycosidases of young albino rats. AB - Impact of thyroidectomy (hypothyroidism) on few glycosidases was studied in the seminal vesicles of young albino rats. Thyroidectomy was performed at 30 days post partum. Seminal vesicular beta-D-glucosidase, beta-D-galactosidase, and N acetyl-beta-D-galactosaminidase exhibited a similar response of decreased activities under short- (30 days) and long-term (60 days) hypothyroid conditions. On the other hand, N-acetyl-beta-D-glucosaminidase registered a temporal biphasic response of increased and decreased activities in the seminal vesicles of rats subjected to short- and long-term hypothyroidism, respectively. The data obtained in the present study suggest that thyroid hormones have specific influences on different glycosidases in the seminal vesicles of rats and euthyroid status is essential for the maintenance of normal activities of these enzymes. PMID- 1874535 TI - Chicken erythrocyte membrane: lipid profile and enzymatic activity under lanthanum chloride and neodymium chloride administration. AB - Acute single dose (ip) administration of two rare earth elements like lanthanum chloride (250 mg/kg body wt) and neodymium chloride (200 mg/kg body wt) to chicks have been found to reduce the activity of certain erythrocyte membrane bound enzymes, viz. acetylcholinesterase, NADH dehydrogenase, Mg(2+)-ATPase, p nitrophenyl phosphatase. Erythrocyte membrane bound glycosidases e.g. beta-D glucosidase, beta-D-galactosidase and beta-D-glucuronidase were also reduced. Other components such as cholesterol and phospholipid residues were reduced but their ratio (cholesterol/phospholipid) remaining unchanged. Membrane sulfhydryl groups were also significantly inhibited by these rare earth elements. PMID- 1874536 TI - Antiulcerogenic and anti-inflammatory effects of emodin, isolated from Rhamnus triquerta wall. AB - Emodin, an anthraquinone derivative, isolated from the whole plant of R. triquerta, in 15 mg/kg dose (ip) exhibited anti-inflammatory activity against carrageenin-induced pedal inflammation in rats. In the same dosage it also showed antiulcer activity against 4 hr pylorus-ligated, aspirin and immobilization stress-induced gastric ulcers in rats. It decreased acid and pepsin output and augmented mucus secretion in terms of total carbohydrate: protein ratio in the gastric juice of aspirin treated pylorus-ligated rats, indicating that the antiulcerogenic effect of emodin may be due to its effect on gastric secretion. PMID- 1874537 TI - Effects of stress on immune responsiveness, gastric ulcerogenesis and plasma corticosterone in rats: modulation by diazepam and naltrexone. AB - Effects of restraint stress (24 hr at room temperature) were evaluated on some immunological, visceral and endocrinal responses in rats. In animals sensitized with sheep RBC (SRBC), restraint stress (a) prevented the booster-induced rise in anti-SRBC antibody titre, (b) induced gastric mucosal erosions, and (c) elevated plasma corticosterone, when compared to non-stressed controls. Diazepam (1 or 10 mg/kg) consistently attenuated the effects of stress on all three parameters studied. The opioid antagonist, naltrexone (1 or 5 mg/kg) tended to aggravate these stress-induced effects. These concurrent biological changes during stress and their modulation by drugs are discussed in light of a possible correlation between endocrinal, immunological and visceral changes during such aversive stimuli. PMID- 1874538 TI - Effects of muscarinic receptor agonists and antagonists on response of non extensor rats to maximal electroshock. AB - Rats which do not respond consistently to maximal electroshock by exhibiting the classical hindlimb extensor response, are designated as 'flexors', and can serve as a useful experimental model for investigating seizure mechanisms. 20-25% Charles Foster rats exhibit the flexor status and were used in this study. The flexor rats were converted to extensors by acetylcholine (icv), physostigmine (ip) and the selective muscarinic M1 receptor agonists, arecholine (ip) and McN-A 343 (icv). This conversion of flexors to extensors was significantly attenuated by M1 receptor antagonists scopolamine (ip) and pirenzepine (icv). The M2 receptor agonist, carbachol (icv), had no effect in lower doses but induced conversion of flexor rats to the extensor status only in very high doses which may be due to loss of receptor specificity on dose increment. The M2 receptor antagonists, gallamine (icv) and AF-DX 116 (ip), also induced significant conversion of flexors to extensors, which was dependent upon the availability of neuronal acetylcholine since the effects were attenuated following pretreatment with hemicholinium, an inhibitor of acetylcholine synthesis. The results suggest that the central cholinergic system has a facilitatory pro-convulsant effect, mediated through the muscarinic M1 receptors, an action modulated by the M2 receptors. PMID- 1874539 TI - Effect of ethanol administration on metabolism of lipids in heart and aorta in isoproterenol induced myocardial infarction in rats. AB - Effect of ethanol administration on the severity of myocardial infarction induced by isoproterenol in rats was studied. Even though serum CPK and GOT levels as well as the extent of myocardial damage as revealed by histopathological studies, were similar, the survival rate was higher in rats administered ethanol. Concentration of cholesterol and triglycerides in the serum and heart in rats given ethanol and isoproterenol seems to be the additive effect caused individually by ethanol and isoproterenol. Myocardial alcohol dehydrogenase and aldehyde dehydrogenase both showed increased activity in rats treated with ethanol. The rate of recovery from myocardial infarction however, was slower in rats treated with ethanol as judged from the serum CPK value. PMID- 1874540 TI - Species difference in intestinal drug metabolising enzymes in mouse, rat and hamster and their inducibility by masheri, a pyrolysed tobacco product. AB - Activities of several drug metabolising enzymes in the small intestine were investigated in Swiss mice, Sprague Dawley rats and Syrian Golden Hamsters fed 10% masheri, a pyrolysed tobacco product, in diet, for 20 months. The basal levels of enzymes in proximal (PI), medium (MI) and distal (DI) parts of the intestine in the three species were similar. However, the levels of cytochrome P 450, benzo(a) pyrene hydroxylase (B(a)OH) and glutathione S-transferase (GST) were highest in hamsters followed by rat and mice. Upon treatment with masheri, significant induction of cytochrome P-450 and B(a)PH was observed in PI and DI of all the three species. However, GSH and GST was depleted upon masheri treatment in all the three species again only in proximal and distal parts of the intestine. Thus increase in activating enzymes together with depletion in GSH-GST system upon exposure could be an important factor in the susceptibility of the small intestine to hazardous xenobiotic exposure. PMID- 1874541 TI - Pathogenesis of cerebral malaria. AB - Plasmodium knowlesi infected rhesus monkeys were employed for investigating brain tissue damage in experimentally induced cerebral malaria. Light microscopic studies revealed parasitic infiltration of virtually all the regions of CNS. Electron microscopic observations confirmed the light microscopic findings. These studies further revealed the presence of macrophages in the blood vessels of infected monkeys. In conclusion, the pathogenesis of cerebral malaria seems to be an outcome of a typical triad consisting of: (1) mechanical obstruction of the blood capillaries by parasitized RBCs; (2) biochemical events, involving free radicals, and (3) immunological dysfunction. PMID- 1874542 TI - Comparison of glucose-6-phosphate dehydrogenase activity in healthy and atretic follicles in rat ovary. AB - Changes in the glucose-6-phosphate dehydrogenase activity have been determined in relation to atresia of Graafian follicles in the rat ovary. Induction of atresia in follicles either due to absence of hCG in the hormonally stimulated immature ovaries or by repeated injections of pentobarbitone sodium to proestrous rats caused significant rise in the enzyme activity. Measurement of enzyme activity in isolated follicular compartments of healthy and atretic follicles revealed that it is significantly higher in the thecal tissue than the granulosa. Increase in enzyme activity in the atretic follicles than the healthy ones occurs due to its rise both in theca and granulosa cells. The significance of these changes in the enzyme activity in healthy and atretic follicles are discussed in relation to the precocious luteinization of cells in the follicular envelope with the onset of atresia. PMID- 1874543 TI - Effect of pinealectomy on daily rhythm of blood glucose in rabbits. AB - Daily rhythm of blood glucose was studied in superior cervical ganglionectomized (SCGX), sham operated and normal rabbits. A typical daily rhythm was observed in normal animals which was not influenced by surgical procedures. However, ganglionectomy, which tantamount to physiological elimination of pineal gland, caused complete reversal of this rhythm. Probable role of pineal gland in controlling blood glucose daily rhythm is suggested. PMID- 1874544 TI - Intraperitoneal toxicity of pea and lentil lectins in albino rats--effect on growth and osmotic fragility of erythrocytes. AB - Lectins from peas and lentils when injected to rats apparently appeared to be non toxic but they caused growth depression. The organ weights were not affected except spleen enlargement. The lectins also caused increased osmotic fragility of erythrocytes without affecting other hematological parameters such as haemoglobin, packed cell volume, and RBC count. PMID- 1874545 TI - Bioconversion of quininone to quinidine by resting cells of Hansenula anomala var. schneggii. PMID- 1874546 TI - Dextran sulfate induced suppression of Plasmodium berghei parasitaemia. AB - Effect of dextran sulfate (DS, Mr 500,000) on parasitaemia in mice (Balb/c) infected with erythrocytic stage of P. berghei was investigated. Intraperitoneal injection of DS caused marked suppression of patent parasitaemia and also enhanced the survival time of the infected animals. PMID- 1874547 TI - Effect of liver extract on growth of Plasmodium vivax in vitro. PMID- 1874548 TI - Binding affinity of leucine-containing chromatin proteins to the polytene X chromosome of Drosophila hydei and its significance. AB - Association of newly synthesised non-histone chromosomal protein to the polytene X chromosome of larval salivary glands of D. hydei has been examined by autoradiographic procedure using 3H-leucine. It has been observed that 3H-leucine labelling pattern is inhibited in presence of puromycin. Results further reveal that there is a reasonable concordance between the binding affinity of newly synthesized protein on the single X chromosome of the male and paired X's of the female. A sitewise analysis of 3H-leucine labelling reveals that although 3H leucine incorporation pattern are not strictly comparable with 3H-RNA synthesis pattern observed under in vivo transcription condition, the labelling pattern with 3H-leucine are not merely the reflection of mass distribution of protein in the polytene chromosomes. Certain aspects of regulation in the organisation of male and female X chromosome in Drosophila by de novo synthesis of protein are discussed. PMID- 1874549 TI - Synergistic effect of heat-shock and UV-irradiation on mitosis and protein synthesis in G2-phase plasmodia of Physarum polycephalum Schw--reduction in UV induced mitotic delay in a preheat-shocked system. AB - The synergistic effect of UV irradiation and heat-shock during the last 3 hr of G2 phase of the cell cycle in the plasmodia of P. polycephalum, in terms of mitotic delay and inhibition of protein synthesis, has been evaluated. The mitotic delay due to both perturbers coordinately increased closer to mitosis. Maximum mitotic delay was obtained in plasmodia heat-shocked after UV irradiation, indicating the presence in this system of either a heat-labile mitogenic substance which is comparatively less susceptible to UV or a substance which is made more susceptible to hyperthermia by UV. A protective role for heat shock applied before irradiation has been observed in that, radiation-induced mitotic delay is significantly reduced in this combination. There was severe inhibition of translation in all the perturbed classes. Organelle level effects which are independent of major protein synthetic activities or different levels of heat-shock protein production could be the reason for the lack of correlation between percentage inhibition of general protein synthesis and the extent of mitotic delay with respect to the two double-perturbed systems. PMID- 1874550 TI - Antigen sharing of Salmonella typhi non-flagellar proteins with other salmonellae and some shigellae and Escherichia coli. AB - Cathodal moving protein components were identified in agarose gel electrophoresis of the Veronal buffer extract of a non-motile strain of S. typhi (8393, Colindale). Rabbit antiserum was raised against these cationic proteins; it had both agglutinating and precipitating activity. A total of 80 salmonella strains belonging to serogroups A, B, C1, C2, D, E1 and E2 including 26 S. typhi and 10 S. paratyphi A were tested against this antiserum in a slide agglutination test; all strains were agglutinated. Among 94 other bacterial strains tested, the antiserum agglutinated all 16 strains of Shigella flexneri, 2 of 5 Shigella sonnei, 5 of 34 E. coli and 1 of 8 Citrobacter species. These results show that there is antigenic sharing of the non-flagellar proteins of S. typhi with many other salmonellae as well as with some shigellae and E. coli. PMID- 1874551 TI - Effect of 12 hr temporal relation of serotonin and dopamine precursor drugs (5 HTP and L-DOPA) on photosexual responses of immature Japanese quail. AB - To study the interaction of photoperiod and circadian neurotransmitter activity, L-DOPA L-dihydroxyphenylalanine, dopamine precursor) was administered daily, 12 hr after 5-HTP (5-hydroxy tryptophan, serotonin precursor) in sexually immature Japanese quail, raised under short photoperiod (LD8:16) since hatching. The 12 hr treatment of 5-HTP and L-DOPA was given under continuous condition of light for 11 days. After treatment the quail were transferred to intermediate day length (LD 13.5:10.5). The cloacal gland size of drug treated group increased significantly in comparison to control. The quail were then transferred to short photoperiod (LD 8:16). The cloacal gland size of both the groups started decreasing gradually but the rate was significantly low in drug treated quail in comparison to control. The results indicate that the endogenous mechanism controlling seasonality may be reset by drugs that influence serotonergic and dopaminergic activity. The 12 hr relation between the two drugs is stimulatory for gonadal growth under intermediate day length and retards the rate of regression when transferred to short days. PMID- 1874552 TI - Suppression of Con A induced lymphocyte transformation by sera from filarial patients with clinical manifestations. AB - Reduced lymphocyte transformation to Wuchereria bancrofti microfilariae excretory secretory antigen and Con A were observed in clinical filarial patients. Pre incubation of normal human peripheral blood mononuclear cells with sera from filarial patients with clinical manifestations such as hydrocele and elephantiasis suppressed Con A induced responses. Effect of fractionated clinical filarial serum on Con A induced lymphocyte transformation showed that the inhibitory activity was associated with high molecular weight serum fraction. PMID- 1874553 TI - Histaminergic mechanisms in experimental convulsions. AB - Effect of some histamine (HA) agonists and antagonists were assessed on electroshock (MES) convulsions in mice and rats. In mice, pretreatment with the HA precursor, l-histidine (100, 500 and 1000 mg/kg) precipitated seizures after a subthreshold (30 mA) stimulus. Both incidence (%) and tonic hind limb extensor phase (THE) were more than that in vehicle treated controls. The H1 blockers, pheniramine (25 mg/kg) and promethazine (25 mg/kg) both protected against (60 mA) MES and both incidence of convulsions and THE were reduced. A similar protective effect was not seen with either the H2 blocker, cimetidine (up to 200 mg/kg), or atropine (1 mg/kg). In rats, both the classical antihistamines blocked MES seizures, whereas, the H2-blocker, cimetidine, and atropine were, ineffective. Further, both H1 blockers were ineffective in antagonizing seizures induced by pentylenetetrazole, INH, caffeine or strychnine. These results are discussed in light of a possible HA-ergic regulation of experimental convulsions. PMID- 1874554 TI - Regression of S-180 sarcoma using a xenogeneic antiserum. AB - Tumour angiogenesis factor (TAF) was extracted from S-180 sarcoma grown as a solid tumour in Swiss albino mice. Its angiogenic activity was detected using the mouse intradermal and the chick chorioallantois membrane assays. Similar extracts from normal tissues failed to induce neovascularisation. An antiserum raised in rabbit, against TAF purified from mouse mammary adenocarcinoma was shown to neutralise the biological activity of TAF from S-180 sarcoma and also caused tumour regression in the mice. A possible therapeutic approach to solid tumours is indicated, as also the preparation of an immunotoxin. PMID- 1874555 TI - Cercal sensory regulation of acetylcholinesterase in nervous system of the cockroach, Periplaneta americana. AB - Cercal ablation caused a significant loss in acetylcholinesterase (AChE) activity of the cercal nerves and terminal ganglion within 12 hr while a similar reduction in enzyme activity of connectives was noticed at least one day after cercectomy. The decrease in AChE activity of the nervous tissues showed a recovery toward control levels from 20 days of unilateral cercectomy whereas the bilateral cercectomy produced a continuous and irreversible decline in enzyme activity. These localized changes in AChE activity of the abdominal nervous system of the cockroach were attributed to be regulated by the cercal sensory innervation. PMID- 1874556 TI - Effects of antihistamines on wound healing. AB - Role of antihistamines (H1 and H2 blockers) in wound healing by utilizing incision and dead space wound models in albino rats was investigated. H1 blockers (mepyramine and promethazine) were found to decrease breaking strength of 10 day old dermal incision wounds and collagen content (as hydroxyproline) and breaking strength of granulation tissue harvested over tubular implant. On the other hand H2 blockers (Cimetidine and ranitidine) did not alter the above parameters. The findings that H1 blockers suppress healing implicate H1 receptors in alleged prohealing effect of histamine, and suggest clinical evaluation of these agents for suppression of overhealing states like keloid, adhesions and strictures. PMID- 1874557 TI - Long-standing rat kidney graft survival by a combination of organ perfusion with MHC class II monoclonal antibody and immunosuppression with reduced doses of 15 deoxyspergualin. PMID- 1874558 TI - Modulatory effects of VIP and related peptides from the gastrointestinal tract on cell mediated cytotoxicity against tumour cells in vitro. AB - In the present study the effect of vasoactive intestinal peptide (VIP), peptide histidine-methionine (PHM), and secretin on spontaneous cell mediated cytotoxicity of peripheral blood mononuclear cells against tumour target cells was evaluated. VIP stimulated cytotoxicity against CaCo-2 human colon cancer cells, whereas less effect was seen against K-562 erythroleukemia cells. Depletion of CD16+ natural killer cells almost completely abolished cytotoxicity and subsequent VIP incubation did not change residual activity. In contrast to PHM, which hardly influenced cytotoxicity, secretin was found to be more effective especially against K-562 target cells. These observations suggest a modulating role for the neuropeptide VIP in the cellular immune response against tumour cells, especially from the colon, resulting in increased activity of CD16+ natural killer cells. Secretin, seems to be less potent in modulating cellular cytotoxicity. These findings support the concept that gastrointestinal peptides can play a role in the regulation of cellular cytotoxicity against tumor cells. PMID- 1874559 TI - Development and use of monoclonal antibodies against an oncofetal protein associated with carcinogenesis and tumorigenesis. AB - An oncofetal protein (OFP) studied in our laboratory associated with embryogenesis, carcinogenesis and tumorigenesis has as its known biological function the modification of RNA release from isolated nuclei. In the present study, we have developed and investigated the use of monoclonal antibodies against OFP. Six hybridoma cell lines (A-F) were isolated by screening the hybridoma culture media for anti-OFP antibodies (MOFP) with an indirect ELISA and by testing the ability of these antibodies complexed with anti-mouse IgG-agarose to bind to rat OFP and remove its associated RNA transport activity from solution (Immunobioassay). An inhibition ELISA developed to measure OFP gave a linear response up to 20 ng of plasma protein from a tumor-bearing rat. Western blot analysis using these monoclonals showed that OFP from a rat tumor (H7777) cytosol that shed to the blood consisted of two species exhibiting molecular weights of 50 and 55 kD respectively. In order to show the usefulness of our assays, a preliminary study showing the ability of the immunobioassay to detect the expression of OFP in the plasma of carcinogen treated rats in a dosage dependent manner has been presented. Since OFP is produced in the target organ of rats shortly after treatment with carcinogens and persists in the preneoplastic foci and subsequent tumors, these monoclonal antibodies will be valuable in studying its involvement in chemical carcinogenesis and tumorigenesis. PMID- 1874560 TI - High susceptibility of cataract Shionogi (CTS) mice to passive anaphylactic shock mediated by allogeneic IgE and IgG1 monoclonal antibodies. AB - The susceptibility of cataract Shionogi (CTS) mice as young as 8 to 10 weeks of age to passive anaphylactic shock mediated by anti-benzylpenicilloyl IgE and IgG1 monoclonal antibodies was compared with those of other strains of the same age including sister strains such as nonobese-diabetic (NOD) and nonobese-nondiabetic (NON). When the animals had been treated with killed Bordetella pertussis organisms, potent sensitization, enough to cause lethal shock, was produced by either monoclonal antibody preparation in CTS, NOD, C57BL/6J and DS/Shi strains, but not at all in C3H/He, DBA/2 and BALB/c strains. In the NON strain, lethal shock was elicited in the animals sensitized with the IgG1 antibody but not in those sensitized with the IgE antibody. Without the pertussis pretreatment, sensitization sufficient to cause lethal shock was produced at a high frequency by the IgG1 antibody in CTS and NOD mice but not in the other strains. When the IgE antibody was used, lethal shock was not observed in any of the mouse strains tested except for one CTS mouse. These results indicate that CTS as well as NOD are highly susceptible strains, and that IgG1 antibody is more effective than IgE antibody for producing systemic sensitization for anaphylactic shock. In addition to these findings, the results revealed an age-dependent potentiation of anaphylactic shock in CTS mice. The IgE antibody-mediated lethal shock was produced in all the aged animals of this mouse strain tested without the Bp treatment, but not in aged NOD and NON mice. PMID- 1874561 TI - Anti-estrogen antibodies in systemic lupus erythematosus: a quantitative evaluation of serum levels. AB - We measured the beta-estradiol binding capacity of serum gamma-globulins in four subject groups; 1) normal men, 2) normal women who had never taken oral contraceptives, 3) normal women who had a history of oral contraceptive use and, 4) patients with systemic lupus erythematosus (SLE). We used dextran-coated charcoal to strip endogenous estradiol from serum proteins, added 3H-estradiol, and measured its association with proteins in various electrophoretic fractions following zone separation on agarose gels. Most of the bound radioactivity was present in the albumin, beta and gamma-globulin fractions. Binding to gamma globulins was elevated in SLE patients, and normal controls who had taken oral contraceptives, as opposed to other controls (p less than 0.005). Gamma-region radioactivity could be removed by protein-G adsorption prior to zone electrophoresis. Isoelectric focusing revealed a pattern of tritiated-E2 binding consistent with polyclonal B-cell activation in all groups. There was no correlation between the extent of gamma-region binding and the total serum immunoglobulin level for any of the groups studied, nor was there a correlation between E2 binding and anti-DNA titers in the SLE group. The average anti estradiol antibody concentrations in SLE sera (assuming equimolar binding) was 105 ng/ml (95% CL = 92-118), whereas their average anti-DNA antibody concentration was in the microgram/ml range. Thus, quantitatively, the level of anti-estradiol antibodies is at least an order of magnitude lower than the anti DNA antibodies characteristic of this disease. PMID- 1874562 TI - c-myc gene in a murine plasmocytoma without visible chromosomal translocations moves to chromosome 12F1 with Pvt-1 and rearranges with IgH enhancer-S mu sequences. AB - The DCPC 21 plasmocytoma lacks any of the MPC-associated chromosomal translocations. However, the c-myc gene has been transposed to the IgH locus on chromosome 12 by an Ig switch-region-mediated recombination mechanism. DNA sequencing analysis, further, revealed that this recombination is consistent with an insertion of the IgH enhancer (E mu)-S mu sequences, 2341 bp in length, into the c-myc 5'-flanking region, resulting in 5': c-myc 5'-flanking-E mu-S mu-c-myc 5'-flanking-c-myc exon-1: 3' segment. In situ molecular hybridization of DCPC 21 metaphase chromosome spreads using a Pvt-1 probe demonstrated that Pvt-1 has also moved to the F1 sub-band region of chromosome 12 where the IgH genes are located. These results indicate that the c-myc gene has been inserted into the IgH locus together with the Pvt-1, regardless of whether plasmocytoma has cytogenetically identifiable translocations. The possible interaction between c-myc activation and Pvt-1 in the development of MPCs is discussed. PMID- 1874563 TI - An autocrine motility factor secreted by the Dunning R-3327 rat prostatic adenocarcinoma cell subtype AT2.1. AB - Tumor cell locomotion is an integral part of the metastatic process. We present a new autocrine motility factor (AMF) derived from the serum-free conditioned medium of the Dunning R-3327 rat prostate adenocarcinoma AT2.1 tumor cell subline AT2.1-AMF, prepared by concentration of components less than or equal to 30 kDa- in size and washed free of low-molecular-weight growth factors, stimulated motility of AT2.1 cells in modified Boyden chamber migration assays. This stimulated migration was dose-dependent, and by checkerboard analysis was both chemotactic and chemokinetic. AT2.1-AMF activity was labile to heat, acid, base, reduction, oxidation, and proteases. Lyophilization and treatment with 6M urea caused a mild decrease (less than 20%) in migration-stimulating capability. Tumor cell specificity was demonstrated for AMF of AT2.1 and AT3.1 Dunning sublines, and the A2058 human melanoma cell lines. AT2.1 cell migration to AT2.1-AMF was inhibited by 2 hr pre-treatment with cholera toxin (0.1 microgram/ml) or forskolin (100 microM), but not altered by 2 hr pre-treatment with pertussis toxin (1.0 microgram/ml). This indicates that guanine nucleotide binding protein mediated regulation of cAMP is involved in modulating the AT2.1 cell response to its AMF. The AT2.1-AMF belongs to a related family of tumor autocrine motility factors and represents a new model for understanding the role of tumor-cell migration in the metastatic process of human prostate cancer. PMID- 1874564 TI - Induction of mammary adenocarcinomas in metallothionein promoter-human growth hormone transgenic mice. AB - To develop transgenic mice, a mouse metallothionein promoter-human growth hormone (Mt-hGH) gene fragment was injected into the pronucleus of C57BI x DBA/2J F2 one cell embryos. Six founder animals grew larger (1.3-2.2 times) than littermate controls and had higher levels of hGH in plasma (4.6-279 mU/l). At 27-43 weeks of age, 3 of the 4 female transgenic founders developed malignant papillary adenocarcinomas of mammary origin. One of the male transgenic founders was successfully mated and 2 of 3 female transgenic offspring developed mammary tumors. Forty-two female mice with the same genetic background as the transgenic animals and older than 43 weeks served as controls. No palpable tumor was found in this group. Five of the control animals were killed and examined histologically, revealing only normal mammary tissue. Earlier studies have shown that GH is important for growth and development of the mammary gland. Our study suggests that markedly elevated endogenous levels of GH cause mammary carcinoma in a specific strain of transgenic mice. The present animal model might be useful for studying molecular mechanisms that are involved in the development of hormonally induced mammary tumors. PMID- 1874565 TI - Interleukin 6 is secreted by breast fibroblasts and stimulates 17 beta-oestradiol oxidoreductase activity of MCF-7 cells: possible paracrine regulation of breast 17 beta-oestradiol levels. AB - Previous studies have demonstrated that cultured human breast fibroblasts secrete a high-molecular-weight polypeptide which stimulates the ability of human breast cancer MCF-7 cells to convert oestrone (E1) to the biologically more active 17 beta-oestradiol (E2). This effect is mediated by an increase in reductive E2 oxidoreductase (EOR) activity. We have identified the fibroblast-derived stimulatory factor as interleukin 6 (IL6) or an immunologically related peptide. Human breast fibroblasts in culture secreted up to 10 ng IL6/ml medium during 24 hr of incubation. The effects of IL6 and breast fibroblast conditioned medium (CM) on reductive EOR activity of MCF-7 cells were similar; both CM and IL6 potently stimulated enzyme activity in a dose-dependent manner, and both exerted synergistic stimulatory effects in combination with E2. A polyclonal neutralizing antibody to IL6 completely abolished the reductive EOR-stimulating activity of CM. These results indicate that breast stromal fibroblasts may have a paracrine role in regulation of breast-cancer-tissue levels of E2, and that this effect is mediated by IL6 or a closely related peptide. PMID- 1874566 TI - TGF beta 1 and TGF beta 2 are potential growth regulators for low-grade and malignant gliomas in vitro: evidence in support of an autocrine hypothesis. AB - Low-grade astrocytomas, anaplastic astrocytomas and glioblastomas in vitro were found to ubiquitously produce the mRNA of transforming growth factor-beta (TGF beta). TGF beta 1 and TGF beta 2 mRNA were expressed to a lesser degree among the hyperdiploid malignant gliomas. By radioreceptor assay of conditioned medium, TGF beta was secreted predominantly in latent form, in both latent and active form, or only in active form within a panel of low-grade and malignant gliomas. The TGF beta receptor (types I, II, and III) was evident among the glioma lines. Many near-diploid gliomas were growth-inhibited by TGF beta 1 and TGF beta 2 in vitro. Most hyperdiploid glioblastomas showed a positive mitogenic response to exogenous TGF beta 1 and TGF beta 2. A synergistic or additive mitogenic interaction with epidermal growth factor and insulin was observed among some. Under serum-free conditions, anti-TGF beta antibody neutralized the expected growth-regulatory effect of endogenous TGF beta, thus establishing the specificity of the response in vitro. TGF beta 1 also enhanced the clonogenicity of certain gliomas which had been growth-stimulated in monolayer. Thus, basic elements in support of an autocrine hypothesis have been demonstrated: TGF beta mRNA was expressed among low-grade and malignant gliomas, TGF beta was secreted in latent and/or active form into conditioned media and appeared to serve as an endogenous regulator of glioma proliferation in vitro. The mitogenic response, either positive or negative, correlated with the degree of anaplasia and karyotypic divergence. PMID- 1874567 TI - Mutational activation of c-Ha-ras genes in intraductal proliferation induced by N nitroso-N-methylurea in rat mammary glands. AB - Although administration of a single dose of N-nitroso-N-methylurea (NMU) to young virgin rats induces a high rate of mammary carcinomas, precise histogenesis of the carcinomas has not been well characterized. In this study, we investigated the alterations of H-ras gene in early focal lesions as well as carcinomas in the mammary glands of F344 rats treated with NMU. At 2 weeks after treatment, intraductal proliferation (IDP) was occasionally observed, and mammary carcinomas emerged at 12 and 36 weeks. The individual lesions of IDP and carcinomas were scooped out from the tissue sections under a stereomicroscope, and the DNA sequence-spanning codon 12 of H-ras gene was amplified from the tissue sections by polymerase chain reaction (PCR). The analysis of amplified DNA by oligonucleotide hybridization revealed that 65% (11/17) of IDP and 89% (16/18) of carcinomas had a point mutation (G-to-A transition) at the 2nd position of H-ras codon 12. However, the DNA amplified from the areas, which appear histologically normal, never showed such mutation. These results indicate that IDP is a very early change for NMU-induced mammary carcinogenesis. PMID- 1874568 TI - A population-based case-control study of endometrial cancer in Shanghai, China. AB - A case-control study of 268 patients with endometrial cancer and 268 population controls was conducted during 1988-1990 in Shanghai, China, to evaluate etiologic factors in a population whose risk had not been substantially altered by the use of exogenous estrogens. In spite of this, the major risk factors resembled those found in other studies. The risk of endometrial cancer was significantly elevated among nulligravidas (OR = 5.4, 95% CI = 2.0-14.6) and decreased with number of pregnancies (p less than 0.01). Late age at menopause was associated with increased risk, while early age at menarche was unrelated. Use of oral contraceptives for more than 2 years was associated with a reduction in endometrial cancer risk (OR = 0.4, 95% CI = 0.1-1.2), while short-term use of oral contraceptives and other methods of contraception were unrelated. Obesity was a strong predictor of risk, with women in the highest quartile of weight having 2.5 times the risk of those in the lowest quartile. In contrast to many other studies, cigarette smokers were at elevated risk (OR = 1.7, 95% CI = 0.9 3.0). Risk was also elevated among women reporting a history of gall-bladder disease, polycystic ovaries, menstrual symptoms, and non-estrogen hormone use. PMID- 1874569 TI - Pooled analysis of 3 European case-control studies: I. Reproductive factors and risk of epithelial ovarian cancer. AB - The role of reproductive factors in the aetiology of epithelial ovarian cancer has been re-assessed in a meta-analysis of 3 hospital-based case-control studies conducted in Europe (i.e. Italy, the United Kingdom and Greece), providing a total dataset of 1,140 cases and 2,724 controls. Multiple logistic regression models were used to obtain relative risk (RR) estimates adjusted for study centre, age, socio-cultural indicators, age at menopause, and oral contraceptive use. The risk decreased with increasing number of births and the trend in risk was significant (chi 2(1) = 7.50, p less than 0.01). In comparison to nulliparous women, those who reported 4 or more births had a 40% reduction in risk of ovarian cancer (RR = 0.6, 95% confidence interval, CI: 0.4-0.8). An RR estimate of 1.4 (95% CI: 1.1-1.7) as found, overall, for age of 35 or more at first birth compared to age of 25 or less at first birth. In each stratum and overall, nulliparous women did not appear to be at increased risk compared to those who delayed birth of their first child until age 35 or more. In each study, as well as in the overall dataset, an inverse association between number of abortions and ovarian cancer risk emerged. Overall, the inverse relationship was highly significant, RR estimates for 1 and 2 or more abortions, as compared to none, being 0.9 (95% CI: 0.8 and 1.1) and 0.7 (95% CI: 0.6-0.9) respectively. The effects of parity, age at first birth and number of abortions emerged consistently in various strata of study centre and age. PMID- 1874570 TI - Pooled analysis of 3 European case-control studies of ovarian cancer: II. Age at menarche and at menopause. AB - The role of age at menarche and at menopause on epithelial ovarian cancer risk was re-assessed in a combined analysis of 3 hospital-based case-control studies conducted in Italy, the United Kingdom and Greece, which produced a total of 1,140 cases and 2,724 controls. In the overall dataset, there was no evidence of an association with age at menarche: compared with women whose menarche occurred at age 15 or over, the relative risk (RR) estimates were 1.0 [95% confidence interval (CI) 0.8 to 1.2] for those with menarche at ages 12 to 14, and 1.0 (95% CI 0.8-1.2) for those with menarche below age 12. There was no consistent interaction between age at menarche and study centre or age at diagnosis. In relation to age at menopause, compared with women whose menopause occurred at age 44 or earlier, the RR was 1.4 between 45 and 49, 1.6 between 50 and 52 and 1.9 above 52. The strength of the association was apparently (but not significantly) greater in the British than in the Greek or Italian dataset. The effect of age at menopause tended to be long-lasting and, if anything, to increase across subsequent age-groups. The large dataset, and the replication of results in different studies, provide more definite and precise information than previously available on the absence of appreciable effect of age at menarche on subsequent ovarian cancer risk in developed countries. For age at menopause, there was a direct and consistent trend in risk, but the association was relatively weak, with RRs below 2 even between extreme categories. PMID- 1874571 TI - Human papillomavirus infection and other risk factors for cervical neoplasia: a case-control study. AB - A case control design has been used to investigate risk factors associated with the development of cervical squamous intraepithelial lesions (SIL) in a population of urban women in which non-affluent minority groups were heavily represented. Eighty-five women with histologically confirmed SIL were compared to a control group of 70 cytologically normal women. HPV infection was determined using both Southern blot hybridization and polymerase chain reaction (PCR) amplification specific for HPV types 16, 18, and 33. When Southern blot was used to detect HPV, logistic regression analysis identified HPV infection (odds ratio (OR) = 17.9, 95% confidence interval (CI) = 6.2-51.6) and low educational achievement (OR = 3.4, 95% CI = 1.2-10.1) as major independent risk factors. When PCR was employed to detect HPV, the logistic regression model suggested that HPV infection (OR = 10.4, 95% CI = 3.6-30.4) and Hispanic ethnicity (OR = 5.0, 95% CI = 1.2-20.5) represented independent risk factors; low educational achievement and Black ethnicity were risk factors of borderline significance. PCR detection of simultaneous co-infection with more than one HPV type was associated with a very high risk of SIL (OR for one type = 7.2, 95% CI = 2.4-21.9; OR for greater than I type = 43.0, 95% CI = 6.9-266.6). Furthermore, increased viral load determined by either method carried an increased risk of disease. HPV infection with viral types previously reported to be related to neoplastic or dysplastic lesions carried the highest risk of SIL. The association of HPV detected by Southern blot and SIL in women less than 35 years old had an OR of 10.1, whereas in women greater than or equal to 35 the OR was 74.5 (p = 0.09 for homogeneity of ORs). We conclude that infection with HPV is the major risk factor for cervical SIL and suggest that targeted HPV screening of women over age 35 may represent an innovative strategy to detect women at high risk of cervical neoplasia. PMID- 1874572 TI - Pooled analysis of 3 European case-control studies of epithelial ovarian cancer: III. Oral contraceptive use. AB - The relationship between use of oral contraceptives (OCs) and other contraceptive methods and the risk of ovarian cancer was examined in a combined analysis of 3 hospital-based case-control studies conducted in Italy, the United Kingdom, and Greece, for a total of 971 ovarian cancer cases and 2,258 controls under age 65. Compared with never-users, the combined multivariate relative risk (RR) for ever users was 0.6 (95% confidence interval, CI = 0.4-0.8) and the estimates were consistent in the 3 datasets. The protection was also similar across strata of age and parity. Considering various measures of OC use, available in the Italian and British datasets only, the protection conveyed on ovarian cancer risk increased with the duration of use and persisted in the medium-long period: the RR in women reporting their last OC use greater than or equal to 15 years prior to diagnosis was 0.5 (95% CI = 0.2-1.0). The risks in ever-users were appreciably lower in those women who reported their first OC use before 25 years of age (RR = 0.3 for first use before age 25, 0.8 for first use at age 25-34 and 0.7 at 35 years or after). Such findings emerged similarly from Italian and British data. This combined analysis, besides offering further quantitative estimates of the protective effects of OCs on ovarian cancer risk in European populations, provides useful insights into the time pattern of the relationship between OC use and ovarian carcinogenesis, suggesting that the protection persists for 15 years or more after cessation of use and may be larger for use at younger age. PMID- 1874573 TI - Derivatives of butyric acid as potential anti-neoplastic agents. AB - A novel derivative of butyric acid, pivalyloxymethyl butyrate (AN-9) has been shown, in vitro, to: (a) induce cytodifferentiation and inhibit the proliferation of leukemic cells; (b) inhibit the growth and formation of Lewis lung carcinoma colonies in semi-solid agar. AN-9 affect cells at about 10-fold lower concentration and at a faster rate than does butyric acid. The pivalyloxymethyl esters of propionic, isobutyric and valeric acids do not elicit effects similar to those of AN-9, while the isobutyryloxymethyl butyrate does, which strongly suggests that the activity of AN-9 stems from intracellular metabolic degradation of the pro-drug to butyric acid. In vivo, AN-9, increased the survival of mice in Lewis lung carcinoma primary cancer model and significantly decreased the number of lung lesions of the animals inoculated with highly metastatic cells, but did not affect their life span. Acute LD50 studies have shown that AN-9 possesses low toxicity. These results suggest that AN-9 is a potential anti-neoplastic agent as well as a tool for investigation of the differentiation induction mechanism. PMID- 1874574 TI - Epidermal growth factor reduces resistance to doxorubicin. AB - Epidermal growth factor (EGF) increased the sensitivity to doxorubicin (DOX) of a human squamous carcinoma cell line, A431. The relative enhancement of sensitivity by EGF was greater in 2 DOX-resistant sublines, A431/A5 and A431/A10, established by growing cells from surviving colonies after treatment of A431 cells with DOX. A greater number of EGF receptors (both high- and low-affinity binding sites) was found for resistant A431/A5 and A431/A10 cells than for parental cells. The enhanced drug responsiveness is not directly related to EGF effects on growth, as growth inhibition by EGF appears to be similar among the 3 sublines. PMID- 1874575 TI - Roles of ovaries and testes in hepatocellular tumorigenesis induced in mice by 3' methyl-4-dimethylaminoazobenzene. AB - The roles of gonads in tumorigenesis induced in mouse liver by 3'-methyl-4 dimethylaminoazobenzene (3'-Me-DAB) were investigated. C57BL/6 x DS-F1 mice which were 10, 12, 14, 16 and 18 days old were treated i.p. with 3'-Me-DAB. Nodular lesions induced in the liver were classified into adenomatous nodules and hepatocellular carcinomas. Adenomatous nodules were composed of a mixture of eosinophilic, basophilic, vacuolated and foamy hepatocytes in various proportions and compressed the adjacent parenchyma. These adenomatous nodules were of monoclonal origin. Carcinomas had a trabecular structure. The incidence, numbers per mouse and areas of adenomatous nodules and carcinomas in male and female mice aged 16-64 weeks were compared. Adenomatous nodules were first detected in males and females aged 24 and 52 weeks, respectively, and their incidences were much higher in males than in females of the same age. The number of adenomatous nodules per mouse and their size were also higher in males. The first carcinoma was found in a 52-week-old male, but no carcinomas were found in females even at 64 weeks of age. The effects of castration 23 days after birth on the appearance of nodular lesions in the livers of 32- to 64-week-old mice were examined. Castration of males did not affect the incidence of adenomatous nodules, but reduced the incidence of carcinomas. It also decreased the number of adenomatous nodules per mouse. Castration of females reduced the time before appearance of adenomatous nodules and increased their incidence, number per mouse, and area. A carcinoma appeared in a 64-week-old castrated female, but no similar lesion was found in intact females of the same age. These results indicate that tumorigenesis induced in mouse liver by 3'-Me-DAB is enhanced by the testes and suppressed by the ovaries. PMID- 1874576 TI - Butyric monosaccharide ester-induced cell differentiation and anti-tumor activity in mice. Importance of their prolonged biological effect for clinical applications in cancer therapy. AB - The interest of butyric salts is based on their capacity to promote differentiation of malignant cells and inhibition of tumor development. The phenotypic modifications are rapidly reversible and require the continuous presence of butyric salts in the target area, which raises problems for therapeutic applications. We show here that the covalent binding of n-butyric acid on natural polyhydroxylated compounds such as monosaccharides, especially 3- or 6-O-butanoyl-1,2-O-isopropylidene-alpha-D-glucofuranose, retains the majority of the biological properties of n-butyric acid. The delayed degradation of these covalent compounds is associated with an improved maintenance of cell differentiation and anti-tumor protection in mice. These butyric complexes thus seem potentially useful for therapeutic applications. PMID- 1874577 TI - Impact of interleukin-2-receptor-targeted cytotoxins on a unique model of murine interleukin-2-receptor-expressing malignancy. AB - DAB486IL-2 is a genetically engineered fusion protein consisting of a portion of diphtheria toxin fused to human IL-2. It is specifically cytotoxic for tumor cells which bear high-affinity IL-2 receptors (IL-2R). DAB389IL-2 is a similarly constructed hybrid protein which is smaller than DAB486IL-2 and is slightly more potent in vitro. We have developed a murine model of IL-2R-expressing malignancy to study the in vivo efficacy of these genetically engineered cytotoxins. Following intravenous administration of CP3 cells, C57BL/6 mice develop tumors which are lymphatic in distribution. When mice are injected i.v. with 10(6) CP3 cells, 90% of the animals show signs of observable tumor by day 10 to 20; death occurs in 50% of untreated animals by day 30. Intravenous treatment of mice with DAB486IL-2 (10 micrograms daily for 10 days), beginning 24 hr after administration of CP3 cells, increases mean survival time by approximately 50%. In comparative studies, DAB389IL-2 is more potent in vivo than DAB486IL-2, with approximately 90% of treated animals with no evidence of tumor at 60 days. The mechanism of action of tumor inhibition by DAB486IL-2 is specific, since treatment of animals which have IL-2R-negative EL4 tumors has not resulted in increased survival time. In addition, treatment of such tumors with DAglu53B486IL 2, a fusion protein which can bind to the IL-2R but is incapable of inhibiting protein synthesis, is ineffective. PMID- 1874579 TI - Pharmacokinetics of fluocinolone acetonide in patch versus cream formulations. AB - The pharmacokinetics of the fluocinolone acetonide patch containing 8 mcg/cm2 and a 0.025% cream were studied in a cross-over trial in 12 healthy volunteers 6 male and 6 female mean age 24.9 years. Each subject was treated with 0.8 mg of both fluocinolone acetonide formulations for 12 h on non-consecutive days. The high performance liquid chromatography method was used to determine the plasma and urine levels of the drug. Minor fluctuations in the plasma profile after patch application were observed, even if no significant difference was found between the two formulations with regard to peak plasma concentration, time to reach peak levels, area under the concentration curve and half-life. PMID- 1874578 TI - Influence of sulbactam plus ampicillin on theophylline clearance. AB - The effect of sulbactam/ampicillin (500 mg/1000 mg) every 12 hours taken for seven days on the steady-state pharmacokinetics of theophylline was studied among 12 patients suffering from chronic obstructive pulmonary disease. Theophylline concentrations were measured serially for 12 h by the method of polarized immunofluorescence (Abbott TDx system). No influence of sulbactam/ampicillin was detectable on the theophylline half-life, clearance or volume of distribution. It was concluded that both drugs could be administered concomitantly without any dosage adjustment of theophylline. PMID- 1874580 TI - Different dosage regimens of ranitidine in the short-term therapy of duodenal ulcer: a multicentre trial. AB - A multicentre clinical trial was conducted in 114 Italian endoscopy centres in order to evaluate the comparative efficacy of four different ranitidine dosage regimens in the short-term treatment of active duodenal ulcer. Results were analysed in a total of 1745 patients randomly allocated to treatment with ranitidine 150 mg twice daily - morning and 19h30 (440 patients), ranitidine 150 mg twice daily - morning and 22h30 (438 patients), ranitidine 300 mg once daily at 19h30 (434 patients) or ranitidine 300 mg once daily at 22h30 (433 patients). The four groups were well matched for patient characteristics at entry. Initial treatment was for three weeks, with continuation to six weeks in cases with endoscopically unhealed ulcers at three weeks. Efficacy was evaluated in terms of endoscopic ulcer healing and control of pain symptoms in 24 h (daytime, nocturnal, daytime plus nocturnal). No statistically significant differences were found between any of the groups either as regards control of pain symptoms or ulcer healing rates (mean healing rates at three and six weeks were 77% and 98%, respectively). The results in this very large patient sample confirm equivalent efficacy of twice daily and single bedtime dose regimens and provide no evidence for superior efficacy of early evening compared with bedtime administration. In the population as a whole, concomitance of the three main risk factors (more than 20 cigarettes/day, ulcer size greater than 1 cm, deformation of the duodenal cap) was associated with a distinctly lower three-week healing rate (40.9% versus 87.4% in patients presenting none of these factors), though this difference tended to disappear at six weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874582 TI - Transference regression and psychoanalytic technique with infantile personalities. AB - This paper describes a particular form of 'silent' regression during the psychoanalytic treatment of infantile personalities (a type of character pathology related to the hysterical personality). This regression is characterized by the development of rapid interchange in the roles enacted in the transference and projected on to the analyst, an apparent 'disconnexion' of the transference material from that dominant when the patient is in non-regressed states, and the intensification of the analyst's counter-transference reactions. The diagnosis and management of these regressive transferences requires a particular interpretive style and strategy outlined in this paper and illustrated with two case vignettes. PMID- 1874581 TI - An in vitro study of the possible interaction between human platelets and cephalosporins. AB - The effects in vitro of four cephalosporins (ceftazidime, cefuroxime, cefotaxime and ceftriaxone) on adenosine diphosphate-induced human platelet aggregation were investigated. Ceftazidime-induced inhibition of platelet aggregation was significant only at a final concentration of 1 mg/ml, whereas ceftriaxone-induced inhibition of platelet aggregation was also significant at a final concentration of 0.01 mg/ml. Cefotaxime and cefuroxime were less active than ceftriaxone. PMID- 1874583 TI - A psychotic organization of the personality. AB - Clinical material is presented to illustrate the difference between psychotic and non-psychotic organizations of the personality. It is suggested that the psychotic part of the personality strives to possess and control its objects because it needs them to repair a damaged ego. The nonpsychotic part on the other hand is able to face reality sufficiently to relinquish its objects and mourn them. The interaction between the two parts in the same patient is discussed. PMID- 1874584 TI - The analysis of an elderly patient. AB - The analysis of a man who was 58 at its beginning is described. Special attention is paid to a seminal fantasy which occurred in the second year. The analysis finished after nine years, and some follow-up assessment is included. PMID- 1874585 TI - The wish for a sex change: a challenge to psychoanalysis? AB - This paper approaches different facets of male transsexualism from the point of view of different current psychoanalytic theories and the criticisms to which some of them give rise. On the basis of the author's observations, the determining psychological factor is stated to be the hatred of masculinity. The central thesis is that the clinical challenge made to psychoanalysis is an integral part of the pathology and that it highlights the working of this disorder, just as the 'reflection theories' of the manifest content of what the patients say represent in their objectifying reification a fundamental aspect of this disturbance. Based on two clinical vignettes, an attempt at reconstruction is proposed, in which the narcissistic aspects of this pathology are emphasized. Current theory tends to stress the concepts of deficit and developmental arrest, which are generally inconsistent with those of conflict and defence, but they are here linked organically together. PMID- 1874586 TI - A dream of the red shoes: separation conflict in the phallic-narcissistic phase. AB - A case is described in which a patient's dream of red shoes stimulated associations to the Hans Christian Andersen fairy tale of The Red Shoes, and the movie of the same name. Analysis of the dream provided valuable insight into the structure and evolution of her neurotic conflicts. At the same time, the symbolic significance of The Red Shoes to this patient helped to clarify one of the meanings of the fairy tale. The interplay of these elements, dream and cultural daydream, within the context of the transference, focused on conflicts in the phallic-narcissistic phase of development, with particular emphasis on separation. PMID- 1874587 TI - Internalization of the absent father. AB - The analysis of a woman, born of an unmarried mother, is presented. Her mental representation of the fantasized father was derived partly from her own wishes and fears, partly from what she was told by her mother, and partly from what she discovered through her own observations and enquiries. The revival in the transference of the split-off parts of her self and of the related bipolarity in her representation of the absent father, the search for their origin in her childhood, the discussion of their operation in her present and past relationships, and the working through of her resistances to change, enabled her to integrate the split-off parts of her self, and to maintain stable relationships. The child's need to internalize a father, whether or not the latter exists in reality, raises the question whether human offspring have an innate propensity to relate to a father, or a father introject, even when the latter is derived from fantasy alone. PMID- 1874588 TI - Adolescence and the repetition compulsion. AB - I describe the connexion between the failure of the procedures of adolescence and the establishment of a psychical economy dominated by the repetition compulsion. The concept of the repetition compulsion appears as early as in 1914, in 'Remembering, repeating and working-through', but is not clearly specified as a characteristic of instinctual functioning until 1919 and 1920, in 'The "Uncanny" and 'Beyond the pleasure principle'. In these two works, Freud presents what amounts to a model of the disorganization of the mental apparatus observed in 'breaks' in the adolescent process when the capacity to bind instinctual excitation in the primary process is swamped. Decompensation is precipitated by the change in the reality principle (de facto infantile impotence becoming adult potency). The repetition compulsion, in the strict sense of the term, is a matter of 'crude', unbound instincts. Moreover, the idea emerges from Freud's two texts that the instinctual demand manifested through the repetition compulsion is the persistence of the incestuous and parricidal wish. This is borne out by my analytical experience, as the two treatments I adduce to illustrate the theory show. PMID- 1874589 TI - Freud's Irma dream: a psychoanalytic interpretation. AB - This paper presents the hypothesis that Freud may have been haunted by the repressed memory of an incident of erotic aggression enacted by himself against his sister Anna when he was 5 years old and she 3 years old. It is suggested that this experience and its psychic ramifications make up the latent content of the Irma dream. The Irma dream is viewed here as the first dream of Freud's self analysis. As in the analysis of the first reported dream in an actual treatment situation, meaning emerges progressively over time. The interpretation proposed in this paper is based on data emerging from 1895 until 1924. Principal sources are 'The interpretation of dreams', which is seen as an associative monologue, the letters to Wilhelm Fliess and Freud's early theoretical works. PMID- 1874590 TI - The psychoanalyst in the mirror: doubts galore but few certainties. AB - The clinical case of a female patient who seemed to be demanding from the analyst changes in her usual technique but in reality wanted her to modify her emotional attitude induced the author to confront the subject of anxiety about change felt to be 'catastrophic', considering it on this occasion from the point of view of the analyst. It is inevitable that the analyst too will initially resort to his or her old defences, succeeding only later by a great deal of hard work in transforming them and putting them in the service of the analysis itself. The main subject of the paper is accompanied by a brief historical digression on the profound changes that have taken place in the years since Freud's death in the way the psychoanalytical movement as a whole thinks of and practises psychoanalysis, culminating in the 'pluralism' mentioned by Wallerstein, and by a personal example of the path travelled day after day by every analyst in his or her consulting room; the overall result is to hearten and encourage us about the future development of our work. PMID- 1874592 TI - On some relationships of fantasies of perfection to the calamities of childhood. AB - In this paper narcissism conceived of as a fantasy of perfection is further redefined within an evolving structural model of psychic conflict. In pursuit of this goal a number of related propositions are explored. 1. A fantasy of perfection is best thought of as a compromise formation. 2. Fantasies of perfection have a development that is influenced, in part, by the development of the calamities of childhood. 3. Fantasies of perfection function as defences to diminish unpleasure associated with conflict. From this perspective a fantasy of perfection is a component of compromise formations. 4. The threat of the loss of the fantasy of perfection evokes anxiety while the sense the loss has occurred is associated with the experience of depressive affect. 5. Fantasies of perfection are important aspects of the compromise formations that constitute the superego. They are also important components of masochistic and narcissistic compromise formations characteristic of aspects of the ego. These compromise formations are intimately related to defensive identificatory relationships between the ego and superego. Analytic data are presented to demonstrate the value of these theoretical considerations. PMID- 1874591 TI - Shame in psychoanalysis: the function of unconscious fantasies. AB - The conceptualization of shame as an emergent affect in the clinical situation gains clarity by linking it to unconscious fantasies. The author suggests that shame appears when an individual fails in his efforts to obtain from another person, in reality or in imagined scenes, an expected similar affect or a complementary message, or both. A self-evaluation emerges of being undeserving of the desired response. In this respect shame is related to the narcissistic component of any experience or fantasy, be it pre-oedipal, oedipal, or post oedipal. In cases where there is a pathological predisposition to shame, the predisposition is linked to unconscious fantasies portraying the individual as the desiring and frustrated subject of an unresponded to affective message. After its formation the unconscious fantasy itself, and all its unrepressed derivatives, become a source of shame. A clinical example illustrates these points. PMID- 1874593 TI - The influence of theory on the psychoanalyst's countertransference. AB - The emotional reaction in the analyst occurs in shared analytic work under the influence of the patient's transference phantasies and is the analyst's creation and contribution. The idea that the analyst has emotions introduced directly into the analyst by the patient such that the analyst contains somebody else's feelings is refuted. Examples have been offered to show how the analyst's working theory influences the countertransference. If the analyst is unaware of this, the analyst may mistakenly attribute negative countertransference to the patient's projection. PMID- 1874594 TI - Penis envy: libidinal metaphor and experiential metonym. AB - The subjective narrative employed by the little girl to account for her femininity draws on her primary sense of femaleness, as well as on any secondary elaborations. The secondary nature of femininity is highlighted by the Freudian view wherein femininity is thought to be achieved through changes in libidinal aims and objects. The primary nature of femininity is highlighted by current views elaborating on ego development. An examination of the subjective role of the phallus in a number of clinical reports reveals that envy of the penis may represent the intersection of several associative chains. For example, the girl's castration reaction could result from a condensation of the libidinal theme of not having a penis as Freud argued. However, Freud's reliance on the phallus as a metaphoric representation of instinctual vicissitudes is not an end point. In addition to Freud's elaborations of the phallic theme, the desire to possess the penis may represent the girl's associations to contiguous events. That is, through the process of displacement, the phallus also functions as a metonymic symbol. To fully appreciate penis envy, both the metaphoric and metonymic meanings assigned to femininity must be analysed. PMID- 1874595 TI - Interpretation and empathy: reading Lacan with Kohut. AB - This paper reads Lacan's exploration of the unconscious through the prism of Kohut's emphasis upon empathy as the basis for psychoanalytic interpretation. Lacan described the disconnexion characterizing human relationships; our experience of each other and of ourselves is radically alienated by the unconscious. Lacan's unconscious is structured like a language, revealing its complexity through symbolic forms. Language and desire always belong to the Other, a dislocation underlying all transferences. In psychoanalysis, transferences provide interpretive access to the language of the unconscious. For Kohut, interpretation depends on the prior establishment of a stable, sustaining transference; human connexion is a lifelong necessity and full understanding an achievable aim. Lacan's more structural approach to the inner world provides an important counterweight to Kohut's narrow preoccupation with the two-person field, while Kohut's concept of maternal mirroring lends a humane dimension to the icy realms of Lacan's intellectual structures. Despite enormous differences, each of these contemporary rediscoverers of Freud's legacy serves to supplement the perspective of the other. PMID- 1874596 TI - On basic unity. PMID- 1874597 TI - Effects of isomeric 2-(arylmethylamino)-1,3-propanediols (AMAPs) and clinically established agents on macromolecular synthesis in P388 and MCF-7 cells. AB - The in vitro effects of the 2-(arylmethylamino)-1,3-propanediols (AMAPs) on macromolecular synthesis have been examined using the murine leukemia, P388, and the human mammary adenocarcinoma, MCF-7, under conditions of short-term drug exposure. AMAPs that were observed to inhibit macromolecular synthesis produced nearly equipotent inhibition of DNA and RNA synthesis. Equivalent inhibition of protein synthesis generally required significantly greater concentrations of AMAP. There is a general correlation between inhibition of polynucleotide synthesis and in vivo antitumor activity. The effects of four clinical candidate AMAPs (crisnatol, 773U82, 502U83, and 7U85) on macromolecular synthesis were further compared with those of actinomycin D, doxorubicin, mitoxantrone, etoposide, amsacrine, and cisplatin in MCF-7 cells. The pattern of AMAP action was most similar to that observed for doxorubicin and mitoxantrone. Finally, the effects of these four AMAPs on the size, specific activity, and rate of incorporation of [3H]-dTTP into DNA of MCF-7 cells synchronized by pretreatment with hydroxyurea was determined. It was found that DNA synthesis was inhibited by AMAPs independent of inhibition of the uptake, phosphorylation, or retention of the metabolic precursors. These results support the theory that antitumor AMAPs interfere with the normal functioning of enzymes, such as topoisomerase II or DNA and RNA polymerases, which interact with DNA. PMID- 1874598 TI - Adozelesin, a selected lead among cyclopropylpyrroloindole analogs of the DNA binding antibiotic, CC-1065. AB - Adozelesin (U-73975) is a potent synthetic cyclopropylpyrroloindole (CPI) analog of the cytotoxic DNA-binding antibiotic, CC-1065. In contrast to the natural product, adozelesin and related CPI analogs do not cause delayed death in non tumored mice. Adozelesin, selected from a series of analogs for its superior in vivo antitumor activity and ease of formulation, is highly active when administered i.v. against i.p. - or s.c.- implanted murine tumors, including L1210 leukemia, B16 melanoma, M5076 sarcoma, and colon 38 carcinoma, and produces long-term survivors in mice bearing i.v.-inoculated L1210 and Lewis lung carcinoma. Modest activity is shown against the highly drug-resistant pancreas 02 carcinoma. Adozelesin is also highly effective against human tumor xenografts s.c.-implanted in athymic (nude) mice, including colon CX-1 adenocarcinoma, lung LX-1 tumor, clear cell Caki-1 carcinoma, and ovarian 2780 carcinoma. Its broad spectrum of in vivo activity compares favorably with three widely used antitumor drugs, i.e. cisplatin, cyclophosphamide, and doxorubicin. Adozelesin appears to be more effective than these drugs in the treatment of very resistant tumors such as s.c.-implanted mouse B16 melanoma, pancreatic 02 carcinoma, and human colon CX 1 and human lung LX-1 tumor xenografts. Based on its high potency and high efficacy against a broad spectrum of experimental tumors, adozelesin was chosen for clinical investigation and development. PMID- 1874599 TI - Comparative toxicity of fostriecin, hepsulfam and pyrazine diazohydroxide to human and murine hematopoietic progenitor cells in vitro. AB - The in vitro myelotoxic potentials of three investigational antitumor agents, Fostriecin, Hepsulfam and pyrazine diazohydroxide (PZDH), were evaluated utilizing clonogenic assays. Human and murine marrow cells were exposed to each drug for 1 hr prior to culture in microcapillary (human) or Petri dish (murine) assays. Fostriecin (0.22-220 microM), Hepsulfam (0.34-340 microM) and PZDH (0.68 680 microM) inhibited myeloid (CFU-gm), erythroid (BFU-e, CFU-e) and megakaryocytic (CFU-meg) colony formation in a concentration-dependent manner. CFU-e from both species were more sensitive to Fostriecin than the other progenitors and murine cells more sensitive overall to Fostriecin than their human counterparts. Murine CFU-e were also more sensitive to Hepsulfam than human CFU-e, with CFU-gm and BFU-e being similarly affected in both species. Human BFU e were greatly inhibited by PZDH, whereas murine BFU-e were relatively resistant to its toxic effects. Fostriecin was the most toxic of the three antitumor agents, with PZDH the least toxic. PMID- 1874600 TI - A novel N-myristylated synthetic octapeptide inhibits protein kinase C activity and partially reverses murine fibrosarcoma cell resistance to adriamycin. AB - This report shows that N-acylation of the protein kinase C (PKC) substrate Arg Lys-Arg-Thr-Leu-Arg-Arg-Leu (RKRTLRRL) provides it with a potent inhibitory activity against PKC. N-myristoyl-RKRTLRRL inhibited Ca2(+)- and phosphatidylserine (PS)-dependent histone phosphorylation catalyzed by PKC with a 50% inhibitory concentration (IC50) of 5 microM, whereas neither RKRTLRRL nor myristic acid inhibited PKC-catalyzed histone phosphorylation at concentrations as high as 50 microM. A fully active, Ca2(+)- and PS-independent catalytic fragment of PKC can be generated by limited proteolysis. N-myristoyl-RKRTLRRL inhibited histone phosphorylation catalyzed by the catalytic fragment of PKC (IC50 = 80 microM), but neither myristic acid nor the nonmyristylated peptide inhibited the activity of the catalytic fragment at concentrations up to and including 200 microM. The Km app and Vmax app for N-myristoyl-RKRTLRRL were similar to those of RKRTLRRL. Thus, N-myristylation provided the octapeptide with an inhibitory activity against PKC but had only minor effects on its Km app and Vmax app. Kinetic analysis provided evidence that the peptide inhibited PKC noncompetitively with respect to ATP. Previously, we reported that the protein kinase inhibitor H7 partially reverses Adriamycin resistance in the multidrug resistant (MDR) murine fibrosarcoma line UV-2237M-ADRR. In this report, we show that N-myristoyl-RKRTLRRL also partially reverses Adriamycin resistance in UV 2237M-ADRR cells. These results suggest that potent and selective cell permeable PKC inhibitors may be designed by N-acylating small PKC peptide substrates. PMID- 1874601 TI - Mitoxantrone, etoposide, mitoguazone and vinblastine chemotherapy (MV2) in relapsed and refractory lymphomas. AB - As part of a program to develop less leukemogenic chemotherapy regimens for the treatment of favorable prognosis Hodgkin's disease, a phase I-II trial of mitoxantrone, etoposide, mitoguazone, and vinblastine was used to treat patients with relapsed and refractory malignant lymphoma and Hodgkin's disease. An overall partial response rate of 41% was observed. Although useful responses were seen, the absence of complete remissions is disappointing. PMID- 1874602 TI - Esorubicin in advanced endometrial cancer: an ineffective and potentially toxic therapy. A Southwest Oncology Group study. AB - The Southwest Oncology Group conducted a phase II study of esorubicin treatment in patients with advanced endometrial cancer who had received no prior chemotherapy. Twenty of 31 patients were fully evaluable for response and toxicity. There were no clinical responses to treatment and 60% (12/20) of the patients developed severe or life threatening leukopenia on therapy. One evaluable patient was removed from study after a cumulative dose of 150 mg/M2 due to a reduction in left ventricular ejection fraction on MUGA scan and another developed congestive heart failure several months after discontinuation of treatment. Esorubicin has significant toxicity and limited clinical activity in patients with advanced endometrial cancer. PMID- 1874603 TI - A phase II clinical trial of diaziquone (AZQ) in the treatment of patients with recurrent leiomyosarcoma of the uterus. A Gynecologic Oncology Group study. AB - Based upon the activity observed in this trial, there does not appear to be a significant role for AZQ as a salvage agent for leiomyosarcoma of the uterus at the dose and schedule tested. PMID- 1874605 TI - Leukoaraiosis: a reappraisal. II. MRI studies. AB - Magnetic resonance imaging is more sensitive than computed tomography to brain white matter changes of undefined significance observed in elderly subjects termed leuko-araiosis. Cross-sectional clinical studies have shown that these changes are more frequent or are more extensive in patients with cerebrovascular disease or vascular risk factors. Pathological studies have revealed that a number of alterations may underlie focal white matter changes including complete and incomplete lacunar infarcts, etat crible, dilated perivascular (Virchow Robin) spaces, demyelination, and gliosis. Diffuse white matter changes are more difficult to explain. These might result from confluence of focal changes, or from diffuse white matter ischemia (incomplete infarct). Alternatively, they may be related to alterations of the transependymal CSF flow. Longitudinal studies in asymptomatic subjects correlating the MRI picture with clinical, pathophysiological, and histopathological data are needed in order to establish the significance and prognostic value of the different processes underlying LA, and to plan therapeutic strategies to prevent or treat them. PMID- 1874604 TI - Hereditary human myopathies in muscle culture. AB - In this article I illustrated the use of regenerating human muscle cultures for studying the hereditary human myopathies. Although some of the data are still controversial, they do point up the great potential of this "in vitro system". For hereditary myopathies due to developmentally regulated proteins that are expressed only at a more advanced stage of muscle differentiation, the use of highly differentiated nerve-muscle cocultures might contribute significantly to a better understanding of their developmental pathogenesis. More advanced techniques (permanent human muscle cell lines, heterokaryons, myoblast transfer, gene transfer, myogenic conversion of human non-muscle cells, cybrid clones) may provide a great deal of information at molecular level and may also have practical applications in the diagnosis or even in the treatment of hereditary human myopathies. PMID- 1874606 TI - Hyperglycemia at ischemic stroke onset as prognostic factor. AB - To find out whether the high blood glucose values sometimes found in the first stage of ischemic stroke have any prognostic value, we considered 76 patients hospitalized within 24 h of an acute cerebral infarction, documented by CT brain scan and/or necropsy, whose fasting blood glucose was recorded before any treatment was given. The patients were sorted into 3 groups: diabetics, normoglycemic non-diabetics and hyperglycemic nondiabetics. On the CT findings cases with large cortical and/or subcortical infarcts were analyzed separately from those with lacunar infarcts. The clinical symptoms on admission proved to be more severe (p less than 0.02) and 30-day mortality higher (p less than 0.02) among the hyperglycemic non-diabetics, who also showed a highly significant (p less than 0.00001) preponderance of large cortical and subcortical infarcts over lacunar infarcts. Multivariate analysis, which took account of variables of known relevance to the prognosis of cerebral infarction (age, sex, arterial hypertension, severity of the clinical pattern, type of brain lesion), confirmed the statistically discriminant power, in terms of mortality, of belonging to the hyperglycemic nondiabetic group. The results of the study confirm that hyperglycemia at stroke onset in nondiabetic patients is an adverse prognostic factor and suggest that it may be a reaction to stress, depending on the size of the infarcted area. PMID- 1874607 TI - Effects of psychotropic drugs on somatosensory evoked potentials in cerebral ischemia. AB - Several authors have demonstrated a correlation between short latency somatosensory evoked potentials (short latency SEPs) and cerebral blood flow (CBF). It is also known that ischemia may modify the amplitude of the cortical SEP while its latency is less sensitive to CBF fluctuations. Phychotropic drugs- Oxiracetam, SAMe, Naloxone, L-acetylcarnitine and GM1--affect some parameters of the early components of cortical SEPs, chiefly the amplitude, which makes SEP recording a useful method for monitoring pharmacological activity in acute stroke. PMID- 1874608 TI - Daytime sleepiness in healthy university students: a multiparametric study. AB - A multiparametric investigation of daytime sleepiness was performed in 18 healthy young university students. After undergoing a standard polysomnographic recording at home the night before, all subjects were evaluated by Multiple sleep latency test (MSLT) at 10.00, 12.00, 14.00, 16.00, 18.00. Subjective sleepiness (by using Visual Analogue Rating Scale) and performance tasks (Cancellation Test, Digit Symbol Substitution, Choice Reaction Time, Critical Flicker Fusion Threshold) were also assessed at the same times. Mean daily sleep latency was found to be about 10 minutes, with several individual values in the borderline range (greater than 5 less than 10 minutes). Subjects did not rate themselves as excessively sleepy and there was no correlation between subjective and objective estimates of sleepiness. No consistent correlation was found between subjective-objective sleepiness and results of performance tests. Anxiety trait (Spielberg State Anxiety Trait) did not correlate with sleepiness, but higher anxiety scores were significantly associated with poor performance. These results confirm the occurrence of fairly marked objective drowsiness in healthy young subjects which, however, was not associated with subjective sleepiness and did not adversely affect performance on a variety of tests of CNS function. PMID- 1874609 TI - Guillain-Barre polyradiculoneuritis after blood transfusion. AB - We report the case of a 72 year-old woman who developed acute polyradiculoneuritis 7 days after a series of 4 blood transfusion. While blood transfusion is not listed as an antedecent event of Guillain-Barre syndrome (GBS), GBS following surgical procedures is well known. In the present case the close temporal relationship and the absence of all factors which usually precede the onset of the disease including surgery, suggest a possible role of blood transfusion in the onset of the GBS. PMID- 1874610 TI - Neuroradiological, neurophysiological and anatomopathological study of a case of locked-in syndrome. AB - We report an anatomoclinical case of locked-in syndrome together with the neuroradiological and neurophysiological findings. MRI confirmed its value in the diagnosis of posterior cranial fossa pathology while the neurophysiological work up (BAEPs, SEPs, MAPs and TEPs) revealed that the lesion may have broader functional implications than may be gauged from the neuroradiological and pathological evidence. Evoked potentials may therefore be of considerable importance in pinpointing brainstem lesions. PMID- 1874611 TI - Acute transient cerebral intoxication induced by low doses of baclofen. AB - We report a case of acute transient encephalopathy with confusion, drowsiness, myoclonic jerks, periodic triphasic sharp wave EEG patterns induced by low doses of baclofen. We discuss the pathogenesis and the differential diagnosis from the subacute spongiform encephalopathy of sudden onset. PMID- 1874612 TI - Irreversible total blindness in multiple sclerosis. PMID- 1874613 TI - Doctor to patient, doctor to colleague: the ethics of medical practice. AB - We were invited to speak at a medical conference on Kauai: "Kauai Calls: People caring for people" held at the Kauai Hilton 21 to 25 February 1991. It was presented by the Society of General Practitioners, the British Columbia Medical Association and the BC Chapter of the College of Family Physicians, all of Canada, together with and by special invitation from the Department of CME of Wilcox Memorial Hospital and the Kauai County Medical Society. David Elpern MD and Paul Esaki MD, of Lihue and Kapaa respectively, were the local sparkplugs and organizers. PMID- 1874614 TI - Patient satisfaction with physician care. AB - Patient satisfaction is known to be related to many desired outcomes in medical care. This study employees multidimensional scaling techniques to identify factors affecting satisfaction with physician care in 1,210 patients. Stepwise regression analysis of factors that met predetermined criteria showed that accessibility explained the greatest amount of variance in patient satisfaction. The patient's perceived efficacy of physician care and greater continuity of care also have significant correlations with satisfaction. Perceived susceptibility to illness, utilization of physician services, and levels of education have lesser but significant effects on patient satisfaction. Despite methodological constraints, economic and psychological benefits make evaluation of patient satisfaction an important exercise. PMID- 1874615 TI - The family as victim in trauma. AB - In trauma, the intense immediate need for medical intervention and stabilization has focused attention on the victim's physical injuries, and away from the traumatic psychosocial impact on his life and family. Trauma teams are prepared to respond quickly and efficiently to sudden life and death situations, with the most up-to-date knowledge, technology and care. Until recently however, little organized, comprehensive attention has been given to the psychosocial responses of the patient and the family. It is now time to prepare ourselves to offer this other important aspect of trauma care--the psychosocial component. As a part of this preparation, I would like to present the Family as Victim in Trauma. PMID- 1874616 TI - [New aspects of UV-therapy of atopic dermatitis]. AB - Atopic dermatitis (AD) is a familial inflammatory skin disease characterized by a typical morphology and distribution and a chronically relapsing course with frequent periods of exacerbation. The management of AD is primarily directed towards symptomatic relief, and treatment decisions depend on cutaneous symptoms at any given time. During periods of acute exacerbation, therapy consists almost exclusively in topical or even systemic corticosteroid therapy. Since long-term corticosteroid therapy is known to have a variety of side-effects, it is important to develop alternative modalities for treatment of AD, such as phototherapy with ultraviolet radiation (PUVA, UV-B, UV-A-B). The major disadvantages of PUVA therapy are the relatively high number of treatments required for healing, the high frequency of rebound phenomena, and as a long-term effect, the potentially increased risk of skin cancer. In contrast, UV-B/UV-A-B therapy is not associated with any major side-effects, but its beneficial effects are clearly limited and usually require several weeks of treatment. Therefore, UV B/UV-A-B therapy is mostly used in combination with corticosteroids for the treatment of acute AD to increase the therapeutic effectiveness. Very recent data indicate that a monotherapy with pure UV-A (340-440 nm) light, if applied in higher doses (15 x 130 J/m2; High-Dose UV-A1), is very effective in the treatment of patients with acute AD. Examination of the photoimmunological events underlying the observed therapeutic effectiveness of High-Dose-UV-A1 therapy may help us to understand the pathophysiological events relevant for AD. PMID- 1874617 TI - [Acquired naevus flammeus (Fegeler syndrome)]. AB - In contrast to common port-wine stains, acquired port-wine stains are extremely rare. We report on an acquired port-wine stain that evolved on the thigh of a 69 year-old male patient and was accompanied by lumbalgia on the same side. Impairment of vegetative nerve fibres by spinal root compression may be considered a causative factor in our patient. PMID- 1874618 TI - [Chlamydia trachomatis serovars and the clinical picture of urogenital infections]. AB - A total of 56 Chlamydia trachomatis strains isolated from female and male patients in the STD outpatient clinic of the Department of Dermatology, University of Heidelberg, were serotyped by means of monoclonal antibodies in an indirect immunofluorescence test. The most prevalent serovar was serovar E, with 35.7%, followed by serovar D, with 28.6%, and serovar F, with 26.8%. No double or multiple infections with different C. trachomatis serovars were found. The first epidemiological study of C. trachomatis serovars in Germany shows that the distribution of distinct serovars is not essentially different from that found in other western countries. The distribution of serovars was similar in women and men. There was no demonstrable correlation between asymptomatic or symptomatic courses of the infections with distinct serovars. In addition, the presence of polymorphonuclear leucocytes in urethritis or cervicitis was not associated with distinct serovars. These results indicate that the antigens used as a criterion in the classification of C. trachomatis are not correlated with the biological behaviour of this infections agent. PMID- 1874619 TI - [Stratum corneum and nail lipids in patients with atopic dermatitis. Decrease in ceramides--a pathogenetic factor in atopic xerosis?]. AB - Dry skin is seen in many patients with atopic dermatitis and correlates with a disturbed epidermal barrier function demonstrated by such features as increased transepidermal water loss and diminished stratum corneum hydration. With regard to the importance of stratum corneum lipids for the permeability barrier, we have analysed plantar (n = 8) and lumbar (n = 20) stratum corneum and nail lipids (n = 15) of atopic subjects by high-performance thin-layer chromatography (HPTLC). Compared with controls our investigations show a decrease in the ceramide fraction as a percentage of total lipid and a diminished ratio of ceramides and free sterols in atopic subjects. This implies that impaired ceramide synthesis may be a factor in the pathogenesis of atopic xerosis. PMID- 1874620 TI - [Benign symmetric Launois-Bensaude type III lipomatosis and Bureau-Barriere syndrome]. AB - We report on a patient with an unusual distribution of benign symmetric Launois Bensaude lipomatosis. In addition, the patient presented with Bureau-Barriere syndrome. With regard to our own observations and those reported in the literature, we propose a new classification of the disease referred to the distribution of the fatty tissue. PMID- 1874621 TI - [Keratosis follicularis--new genetic aspects]. AB - A hypothesis according to which two types of keratosis follicularis (below) should be differentiated is discussed with reference to clinical findings recorded during mass screening in kindergartens and in a dermatological practice: (1) condition improves, to normal in early adulthood, a type in which the for which heritability not cannot be identified by mass screening; (2) a type with growing incidence, primarily among women up to 30 years of age, caused by an X linked dominant gene. PMID- 1874622 TI - [Psoriasis in a female chimpanzee]. AB - Psoriasis, a widespread genodermatosis in Homo sapiens, also appears in primates. We report on a female chimpanzee in Leipzig Zoo. After years of captivity the animal developed erythematosquamous, highly hyperkeratotic, lesions, some confluent, on the knees, elbows, back of the hands and feet and on the forearms and the seat, which showed histologically characteristic features of psoriasis. It may be that both previous infections and psychic stress resulting from social isolation had caused eruption of the disease. In the literature single cases of psoriasiform dermatoses have also been described in other species of monkeys and even in a springer spaniel. Nonetheless, the search for an animal model of psoriasis vulgaris is still going on. PMID- 1874624 TI - [Sulfones in alopecia areata]. PMID- 1874623 TI - [Sneddon syndrome]. AB - A 44-year-old female with Sneddon's syndrome, i.e. generalized racemose livedo and recurrent cerebrovascular disease, is presented. Significant levels of IgG anticardiolipin antibodies were found in her serum. PMID- 1874625 TI - [Pyrethrins/pyrethroids in epizootic infestation]. PMID- 1874626 TI - [Principles of rational therapy with external glucocorticosteroids]. PMID- 1874628 TI - Constriction in biopsy/suction channel of olympus CF-1T100L and CF-V10L colonoscopes. PMID- 1874627 TI - Fiber-delivery lasers: Nd:YAG, argon, and KTP/532. PMID- 1874629 TI - Bemis Wall-Safe needle-disposal units. PMID- 1874630 TI - Mechanical stop failure on Storz APEX 2000/2100 ENT chairs. PMID- 1874631 TI - [Diagnosis of allergic rhinitis. II. Laboratory studies--milieu analysis- literature]. PMID- 1874632 TI - [Experimental studies of the physiology of the paranasal sinuses]. AB - The mucociliary clearance of the maxillary sinus mucosa was studied by 99mTc-SC in 38 healthy subjects. The mucociliary transport rate was relatively constant under physiological conditions so that it was possible to describe a normal range with a narrow variation. This range can be used to estimate the physiological responses of the mucociliary apparatus, and to define pathological disorders. In 3 cases we saw a slow clearance which has never been described before in the sinuses. In our experimental study we showed that the mucociliary activity of the sinuses is not only a mechanism to clean the mucosa, but is moreover a controlled system which can be activated by a physiological stimulus. After the stimulation the production of mucus and its outflow to the nose increased. Physiological and phylogenetic aspects of the existence of the sinuses in vertebrates and man are discussed. PMID- 1874633 TI - [Nuclear medicine studies of the regenerative behavior of paranasal sinus mucosa after functional endoscopic ethmoid bone surgery]. AB - The mucociliary clearance of the maxillary sinus mucosa was studied before and 6 18 months after functional sinus surgery using 99mTc-SC in 34 sinuses of 22 patients with chronic inflammation of the ethmoid and maxillary sinus. Before operation the mucociliary transport was very slow and sometimes absent. In the postoperative interval between 6 and 18 months we saw a significant return of the mucosal function. In 56% of the sinuses investigated the postoperative clearance rate was within the normal range. We also recorded a similar trend in allergic patients, although there was not such a clear return to normal of the mucociliary clearance, and the rates were not within the normal range. We found no recovery of the mucociliary function in 11 sinuses of 7 patients with impaired healing. Decisions on subsequent treatment were based on postoperative nasal endoscopy and functional mucosal repair. PMID- 1874634 TI - [Risks of a cartilage-bone bank with reference to HIV infection]. AB - Allogenic transplants have an established place in reconstructive procedures. For years it has been suspected that lyophilized dura mater can transmit Creutzfeld Jakob disease. HIV infection with fully manifest AIDS and a mortality of up to 100% is now also increasing in significance. It is necessary to assess the risk of transferring HIV with allogenic transplants because HIV passes into the cell via specific surface receptors and is integrated within the chromosome. Experimental data on disinfection and sterilization of allogenic transplants stored within chromosomes and their inactivation are not available. Allogenic transplants are only used in operations for life-threatening disease. As a rule, these are elective operations which must meet the highest safety standards, also with regard to the danger of infection. Collaboration with a transplantation team is essential. PMID- 1874635 TI - [Allergic origin of recurrent middle ear effusion and adenoids in young children]. AB - Recurrent middle ear effusions and adenoids in children might be caused by mechanical obstruction, infection or allergy. From 1989 to 1990 we examined 35 infants with no history of allergic rhinitis but with recurrent adenoids and middle ear effusions. During operation a skin test was performed for common allergens. Afterwards we tried to identify these allergens by RAST tests on tissue homogenates from the removed adenoids, the middle ear effusion and serum samples. Additionally the IgE levels were determined and the adenoid tissue was examined for eosinophils. In 12 of our 35 children (34%) the skin tests showed an allergy, mostly to different kinds of pollen or house dust. From these positive patients the respective allergens could be determined by RAST tests in serum in 84%, in tissue homogenates from the adenoids in 41% and in the middle ear effusions in 50% of cases. 50% of the children with positive skin tests showed an eosinophilia in the adenoid tissue. We did not find any allergen in the RAST of the infants with negative skin tests. The data show a correlation of allergen specific IgE antibodies in the serum of our patients and in the middle ear and the nasopharynx. Together with an eosinophilia these results suggest an allergic genesis of recurrent middle ear effusions and adenoids in about 20% to 30% of our cases. Early diagnostic procedures to rule out allergy in children with appropriate clinical symptoms are useful, and in positive cases antiallergic treatment is recommended. PMID- 1874636 TI - [Diagnostic value of the prick test and tissue RAST in allergic nasal polyposis]. AB - Nasal polyposis is often accompanied by an allergy against inhaled allergens or various foods and drugs. We studied the relationship between nasal polyposis and type-I allergy, using a preoperative skin test on 43 patients with nasal polyposis. This was followed by RAST test of serum, nasal secretion and homogenized tissue from the polyps removed. The rest of the polyp material was examined histologically and cytologically for tissue eosinophilia. A type-I allergy was proved in 40% of the patients by the presence of the same IgE antibodies in the skin test and all the RASTs, accompanied by a distinct eosinophilia in the polyp tissue. In a further 40% of the cases most of the tests were positive, suggesting a probable allergic disposition. These results support the theory of an allergic genesis of many nasal polyps. The tissue RAST especially is of great diagnostic value. Thus, postoperative anti-allergic treatment of these patients should be successful. PMID- 1874637 TI - [Cholesteatoma and chronic tubal middle ear infection in children. A 10 year overview]. AB - Over a 10-year period we observed 99 cholesteatomas. In 62% the cholesteatomas lay in the epitympanum, in 18% they lay behind an intact tympanic membrane, and in 18% in the posterior-superior portion of the pars tensa. There were 2 cases of iatrogenic cholesteatoma following insertion of ventilation tubes. In the same period we saw 1229 children suffering from chronic serous otitis media (SOM). A total of 1918 ventilation tubes were inserted in 856 children with SOM, so that the incidence of iatrogenic cholesteatomas is extremely low at 0.1%. Our findings indicate that cholesteatomas in the posterior-superior portion of the pars tensa are more often caused by disturbed ventilation due to SOM than are epitympanic cholesteatomas. Furthermore myringotomy and ventilation tube insertion is not only a means of treating SOM, but it can also reveal a hidden cholesteatoma. Long term follow-up of children treated for SOM is necessary in order to recognise cholesteatomas and adhesive processes at an early stage. PMID- 1874638 TI - [Functional nasopharyngeal fiberoptic endoscopy for pre-therapeutic diagnosis of sleep apnea syndrome in infants. A case report]. AB - We report a 2-year-old infant with severe obstructive sleep apnoea. The symptoms had deteriorated for several months, and indicated complete obstruction shortly after the child fell asleep, with reduction of the oxygen saturation to under 30%. Since the obstruction could only be interrupted by waking the child, a tracheostomy was proposed. Endoscopy under general anaesthesia revealed no pathological findings. The stenosis could only be seen using transnasal fibre optic endoscopy when the obstruction occurred during sleep: the oropharyngeal wall collapsed at the level of the velopharyngeal sphincter. A tube passed through the nose and through the collapsing section of the pharynx to the entrance of the larynx prevented the apnoea. The parents were taught to introduce and fix the tube. After an observation period of 1 year the larynx had stabilized spontaneously, and the tube has to be introduced only rarely. PMID- 1874639 TI - Minicomputer software programs aid critical care. PMID- 1874640 TI - Dr Irvin set standards for evaluating lateral sacral tilting. PMID- 1874641 TI - Controversial findings of VA AZT trial. PMID- 1874642 TI - Taking a different look at so-called burnout. PMID- 1874643 TI - External cephalic version of term singleton breech presentations with tocolysis: a retrospective study in a community hospital. AB - External version with the use of tocolysis in low-risk patients has been shown to be relatively safe and effective. A retrospective analysis was undertaken to see if version was practical for a smaller community-based hospital. Thirty-two antepartum external cephalic versions with ritodrine tocolysis during a 4-year period were reviewed. Successful version occurred in 59.4% of attempts. Of patients with a successful version, 68.4% delivered vaginally. One successful version occurred spontaneously with ritodrine tocolysis alone. A stillbirth due to abruptio placentae occurred 20 hours after a failed version attempt. PMID- 1874644 TI - Gallbladder disease and coronary artery disease: is there a link? AB - Both gallstones and coronary artery disease are associated with cholesterol. Therefore, the literature was searched for evidence that gallbladder disease can be considered a risk factor for coronary artery disease. The problem has been approached from several angles. Studies designed to discover whether lipid profiles associated with gallbladder disease are similar to those associated with coronary artery disease have shown contradictory results. Autopsy studies have indicated that atherosclerosis appeared to be more extensive in patients with gallstones, but, again it was unclear whether the relationship was causal or merely reflected coincidental factors of some other origin. A study attempting to find a relationship between gallstone formation and a low-cholesterol diet actually showed a higher rate of gallstone formation among the patients on the low-cholesterol diet. Possible explanations for the results of these various studies are offered. PMID- 1874645 TI - A selective approach to operative cholangiography. AB - The value of operative cholangiography in the detection of common bile duct stones has been documented in a number of studies. This study suggests that operative cholangiography can be-used successfully on a more selective basis when used in conjunction with laboratory and operative criteria. One hundred and fifty patients who underwent routine cholecystectomy were retrospectively evaluated. Seventy-five percent had a normal cholangiogram and normal levels of bilirubin and alkaline phosphatase. The remaining 25% had abnormal cholangiograms as well as abnormal laboratory chemistry values. It was noted that if selective operative cholangiography had been performed only on those patients with indications for common bile duct exploration, no ductal stones would have been omitted. Based on these data, a selective approach to operative cholangiography is advocated. PMID- 1874646 TI - Mycobacterium tuberculosis in the acquired immunodeficiency syndrome. AB - Patients with human immunodeficiency virus (HIV) infection, with or without the diagnosis of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), have an increased incidence of tuberculosis, especially of an extrapulmonary nature. The condition is associated with significant morbidity and mortality. The reported incidence of the combination of tuberculosis and AIDS varies between 4% and 10% of AIDS patients, with a higher incidence noted in the male, inner-city, intravenous-drug-abuser population. Clinical findings may reflect the site of infection, but are often nondiagnostic. Diagnosis often requires biopsy for histopathologic evaluation and tissue culture to document the presence of granulomas and mycobacterial organisms. Universal body fluid precautions among these patients are mandatory, and respiratory isolation should be maintained during diagnostic evaluation and early treatment. These patients usually respond to standard antituberculosis therapy. Physicians should maintain a high index of suspicion of tuberculosis in patients with HIV infection. Conversely, the diagnosis of HIV infection should be considered in patients with unusual manifestations of tuberculosis. Because tuberculosis is one of the few potentially curable infections in the AIDS patient, recognition of its presence is crucial. PMID- 1874647 TI - Drugs of abuse testing. AB - Modern medical technology has made available a complex array of testing methods for drugs of abuse. The gathering of the best information from these methods demands that the clinician be familiar with the different testing protocols. In this, the third article in a monthly series, the authors discuss the more common and useful tests and describe their use for optimal results. PMID- 1874648 TI - Atrial fibrillation during a subarachnoid block in a patient with undiagnosed mitral valve prolapse. AB - Mitral valve prolapse (MVP) is a common cardiac abnormality, and there are numerous documented cases of intraoperative dysrhythmias. However, the authors describe what is believed to be the first case of atrial fibrillation in a patient with an undiagnosed MVP who was given a subarachnoid block. A possible clinical sequencing for the subarachnoid block is offered. The differential diagnosis, etiology, pathology, and pathophysiology of MVP are discussed. Also detailed are the management of intraoperative dysrhythmias. Physicians should be aware, as in the case reported, that a new-onset atrial fibrillation can occur, even without previously diagnosed MVP. PMID- 1874649 TI - Patients' right to know if their physician has the acquired immunodeficiency disease (AIDS) outweighs the physician's right to privacy. PMID- 1874650 TI - Most Americans favor tough criminal laws. PMID- 1874651 TI - Epoetin alpha approved for anemic AIDS patients. PMID- 1874652 TI - Lyme disease: the bite of spring becomes the (diagnostic) menace of summer. PMID- 1874653 TI - Understanding antinuclear antibodies. AB - The American College of Rheumatology (formerly the American Rheumatism Association) diagnostic criteria for connective tissue disorders frequently include positive antinuclear antibody (ANA) assays. Proper interpretation of these tests requires an understanding of the principles governing ANA assays. Assay results are reported in two ways: as titers and as descriptions of fluorescent patterns. A titer is a quantitative measure of ANAs in serum. Different patterns of immunofluorescence are associated with different subsets of collagen vascular disease. Positive results can occur in the absence of connective tissue disease. Accurate diagnosis of connective tissue disorders requires judicious use of ANA assays as well as skillful interpretation of the results. PMID- 1874654 TI - Lyme borreliosis: detecting the great imitator. AB - Lyme disease is a common inflammatory disease of North America. It is caused by the spirochetal bacterium Borrelia burgdorferi, which is transmitted by the bite of a small tick, Ixodes dammini. The disease is inconsistent in its manifestation, mimicking a wide variety of maladies, many of which are noninfectious. Currently, there is no practical means for detection of the presence of the organism, and serologic studies offer the best diagnostic aid. High titers of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to B burgdorferi antigens indicate disease, but lower titers can be misleading. The IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years. Antibiotic therapy early in the infection may interfere with antibody production, but therapy later does not appear to have a significant effect on antibody levels. Because several methods are available for the detection of antibodies and several choices for antibody detected--IgM, IgG, or combinations--the clinical laboratory should provide guidance and advice in choosing and interpreting tests. PMID- 1874655 TI - Atrial septal aneurysm as a cause of abnormal left atrial flow: an echocardiographic study. AB - Atrial septal aneurysms, although rare, are being found with an ever increasing frequency through the technology of two-dimensional echocardiography. In this article, we report the identification of an atrial septal aneurysm and abnormal systolic flow toward the transducer and mitral valve by use of two-dimensional echocardiography with pulsed-wave Doppler capability. PMID- 1874656 TI - Coumarin-induced skin necrosis. AB - Coumarin skin necrosis is a rare and usually unpredictable complication of coumarin therapy, occasionally leading to death. Onset is usually between the third and sixth day of coumarin therapy. The patient most commonly complains of pain in a region of abundant subcutaneous fat, with progression to erythema, petechiae, and gangrenous necrosis. Thrombosis of the dermal and the subcutaneous veins is demonstrated pathologically. We describe a case and review the pathogenesis, treatment, and prevention of this lesion. PMID- 1874657 TI - Hemangiopericytoma of the breast. AB - Hemangiopericytoma is an extremely rare soft tissue tumor of the pericytes that surround the walls of blood vessels. The lesion is characterized by proliferation of the pericytes above the basement membrane. The microscopic features of the hemangiopericytoma can often be demonstrated by reticulin staining. Clinical presentation can vary. The lesion has been found in any number of anatomic locations. Occurrence in breast tissue, however, has been strikingly rare. Most lesions are benign. However, they can be aggressive and can recur at distant sites. Malignant varieties have been reported. In breast tissue, the most difficult aspect of the diagnosis appears to be that the tumor grossly, and to some extent microscopically, resembles cystosarcoma phylloides, particularly in the malignant degenerative form of the latter disease. Most diagnostic methods for evaluating the tumor fail to produce a definitive diagnosis. Microscopic confirmation is perhaps the only method by which definitive diagnosis can be made. Treatment consists of wide excision and careful clinical follow-up. A case history and a review of the literature concerning this lesion are included here. PMID- 1874658 TI - Thymic squamous cell carcinoma. AB - In the case described, a 43-year-old man had an asymptomatic mass involving the right hilar and superior mediastinum. At surgery, the tumor was found to have invaded the right middle lobe of the lung and the pericardium. The mass was found to be a thymic squamous cell carcinoma, a rare tumor. Two serum tumor markers- lipid-associated sialic acid and squamous cell carcinoma antigen--were elevated. The patient underwent postoperative radiation therapy and has responded favorably to treatment. He had no clinical evidence of metastasis or recurrence as of 43 months postoperatively. PMID- 1874659 TI - Pet overpopulation. PMID- 1874660 TI - Concerned about scrapie. PMID- 1874661 TI - Two years as a veterinarian in Africa: thoughts and observations. PMID- 1874662 TI - From veterinary student to professor to private practitioner. PMID- 1874664 TI - The veterinarian's oath: are you keeping your promise? PMID- 1874663 TI - Logistic regression and discriminant analysis. PMID- 1874665 TI - The veterinarian as third party defendant. PMID- 1874666 TI - Personal relationships in the veterinary clinic. PMID- 1874667 TI - Principles of magnetic resonance imaging and application to the stifle joint in dogs. PMID- 1874668 TI - ECG of the month. PMID- 1874669 TI - Effect of tissue adhesives and suture patterns on experimentally induced teat lacerations in lactating dairy cattle. AB - Tissue adhesives and suture materials were evaluated for repair of experimentally induced teat lacerations in 6 lactating dairy cows. Group-1 teat lacerations were not closed and served as nonsutured controls. Group-2 lacerations were closed in three layers (mucosa, submucosa, and skin) by use of 3-0 polydioxanone. Group-3 lacerations were closed by use of N-butyl cyanoacrylate monomer tissue adhesive. Group-4 lacerations were closed by use of a combination of sutures and tissue adhesive. All cows were milked by machine. Healing was observed for 28 days, then cows were slaughtered, and teats were recovered for further study. Evaluation revealed failure of healing of all layers with formation of large fistulas in 3 of 4 nonsutured control teats in group 1. All 6 teat lacerations in groups 2 and 3 healed satisfactorily with no fistulas. Five of 6 teats in group 4 had partial healing of skin and mucosa with no fistulas, and 1 teat failed to heal and developed a small fistula. Data indicated that closure of experimentally induced teat lacerations with three layers of fine absorbable suture or closure with tissue adhesive alone gave good results and satisfactory healing of all layers. However, when sutures and tissue adhesive were used together, foreign body reaction was marked, and the skin and submucosa healed only partially. Sutures appeared to entrap the tissue adhesive, resulting in a foreign body reaction. PMID- 1874670 TI - Xanthine-containing urinary calculi in dogs given allopurinol. AB - Clinical features and laboratory findings were evaluated in 10 dogs that formed xanthine-containing urinary calculi during the period that they were given allopurinol (9 to 38 mg/kg of body weight/d). Duration of allopurinol treatment was 5 weeks to 6 years. Of the 10 dogs, 9 (all Dalmatians) had formed uric acid containing calculi at least once before allopurinol treatment was initiated. It was not possible to recognize xanthine as a crystalline component of the calculi by use of a chemical colorimetric method or by polarized light microscopy. We concluded that the best diagnostic method for recognition of xanthine-containing calculi was high-pressure liquid chromatography because it is quantitative, sensitive, and accurate, and can be conducted on a small amount (1 to 2 mg) of crystalline material. PMID- 1874671 TI - Evaluation of surgical scrub and antiseptic solutions for surgical preparation of canine paws. AB - The purpose of the prospective study reported here was to evaluate surgical preparation of canine paws. Three combinations of surgical scrub solutions and antiseptic solutions were used: (1) 7.5% povidone-iodine scrub/10% povidone iodine solution; (2) 2% chlorhexidine acetate scrub/2% chlorhexidine diacetate solution; and (3) tincture of green soap/70% isopropyl alcohol. The control was warm (38 to 42 C) tap water. Four microbial colony counts were used to evaluate surgical preparation of 4 paws of 8 dogs. Specimens were obtained from the paws for a baseline microbial flora count. After surgical scrub was performed, additional specimens were obtained for bacteriologic culturing. Antiseptic was applied followed by collection of another specimen for bacteriologic culturing. A final specimen was obtained following a 24-hour period under a sterile occlusive bandage. The 3 scrub solutions and the tap water control resulted in lower colony counts following scrubbing of the paws; however, only the 3 antiseptic solutions resulted in further colony count reduction after their application. Evaluation of residual colony counts isolated from specimens taken after a 24-hour period under a sterile occlusive bandage revealed chlorhexidine and povidone-iodine scrub/antiseptic combinations to be similar in antibacterial activity, with significantly (P less than or equal to 0.05) lower colony counts than those from specimens of paws treated with either the tincture of green soap/isopropyl alcohol combination or the tap water control. The lack of a significant difference between the bacterial counts immediately after surgical preparation with povidone-iodine and chlorhexidine and their respective 24-hour residual counts, indicated no particular advantage to surgical preparation and occlusive bandaging 24 hours prior to surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874672 TI - Comparison of the efficacy of ivermectin, oxibendazole, and pyrantel pamoate against 28-day Parascaris equorum larvae in the intestine of pony foals. AB - Sixteen helminth-free pony foals were inoculated with a mean (+/- SD) 2,000 (+/- 545.5) infective Parascaris equorum eggs (day 0). Foals were allocated to replicates of 4, and treatments within each replicate were assigned at random. Treatment administered on postinoculation day (PID) 28 included no treatment (control), 0.2 mg of ivermectin/kg of body weight, 10 mg of oxibendazole/kg, or 6.6 mg of pyrantel base (pamoate)/kg. Paste formulations of the anthelmintics were administered orally. The foals were euthanatized 14 days after treatment (PID 42) and examined for P equorum larvae in the small intestine. The mean +/- SD (and range) numbers of fourth-stage P equorum larvae recovered from nontreated foals and those treated with ivermectin, pyrantel, or oxibendazole were 1,603.8 +/- 1,026.8 (305 to 2,480), 29.3 +/- 55.8 (0 to 113), 413.0 +/- 568.1 (0 to 1,204), or 889.5 +/- 1,123.1 (1 to 2,345), respectively. Compared with the value for control (nontreated) foals, treatment with ivermectin, pyrantel, and oxibendazole was 98.2, 74.2, and 44.5% effective, respectively, when administered 28 days after experimentally induced infection with P equorum. Adverse reactions attributable to treatment were not observed. PMID- 1874673 TI - Adherent gram-positive cocci on the intestinal villi of two dogs with gastrointestinal disease. AB - Two dogs were examined for clinical signs of chronic gastrointestinal disease. Duodenal mucosal biopsy specimens, obtained endoscopically, revealed histologic lesions of adherent gram-positive cocci on the villus epithelium of both dogs. The positive gram stain and morphologic features of the adherent cocci were suggestive of Streptococcus organisms. Indirect tests for intestinal bacterial overgrowth were not diagnostic, suggesting that the adherent cocci were a primary lesion. Rapid clinical response following dietary manipulation and the initiation of medical management was observed in both dogs. The dogs of this report draw similarities to Streptococcus durans infection previously reported in pigs, foals, and a single pup. The pathogenesis of enteric disease associated with adherent gram-positive cocci in dogs remains ill-defined. PMID- 1874674 TI - Two-dimensional echocardiographically guided pericardiocentesis in a horse with traumatic pericarditis. AB - Two-dimensional echocardiographic (2DE) examination was performed on a horse with clinical signs of pericardial effusion. Thickening of the pericardium, excess amount of pericardial fluid, elevation of the cardiac apex, and right ventricular compression, characteristic of cardiac tamponade, could be seen on 2DE recordings. Fibrinous pericarditis was suspected by observation of fibrinous strands in the pericardial fluid and epicardial fibrin deposits. Echocardiographically guided pericardiocentesis was performed, and 4 L of fluid was removed from the pericardial sac. Streptococcus zooepidemicus was isolated from the fluid. Pericardiocentesis was repeated for 3 days, and medication was administered. Despite temporary improvement in cardiac function, the horse's condition deteriorated gradually, and euthanasia was performed on the ninth day of hospitalization. Necropsy revealed chronic serofibrinous pericarditis of traumatic origin, attributable to an intercostal stab wound entering the pericardium and the apical portion of the myocardium. PMID- 1874675 TI - Cosmetic repair of a facial deformity by use of a silicone implant in a horse. AB - A heat-vulcanized silicone implant was used for cosmetic repair of a facial deformity in a horse. The deformity had resulted from fracture of the frontal bone into the frontal sinus 6 months earlier. Normal facial contour was restored by suturing the sculpted implant to the periosteum over the defect. Results 1 year after surgery were excellent. PMID- 1874676 TI - Psittacine proventricular dilatation syndrome in an umbrella cockatoo. AB - Psittacine proventricular dilatation syndrome (macaw wasting disease) is a fatal disease of the gastrointestinal tract and, sometimes, the CNS. The disease most often affects macaws and is thought to be of viral origin. An Umbrella cockatoo was referred with signs of neurologic dysfunction. Other unusual findings included flaccid crop, distended duodenum, and acute weight loss. Because treatment has not been reported to be effective, the affected cockatoo was euthanatized to limit spread of the disease. PMID- 1874677 TI - Management of vertebral column fractures in dogs and cats: 211 cases (1977-1985). AB - Hospital records and radiographs of 211 dogs and cats with vertebral column fractures or luxations evaluated at the University of Tennessee Veterinary Teaching Hospital between April 1977 and September 1985 were reviewed. After neurologic examination, status of the animal was graded on a scale of 1 to 8. Decision to treat each animal either medically or surgically was based on the extent and type of injury, neurologic signs, veterinarian's experience, and owner's wishes. After treatment, neurologic status was evaluated on the aforementioned scale and differences in the outcome of treatment were determined between surgically and medically treated groups, relative to initial neurologic status and location of the fracture. Surgically treated animals had pretreatment mean (+/- SD) neurologic status (3.71 +/- 1.35) that was slightly worse (P = 0.0079) than that of medically managed cases (5.16 +/- 1.48). Animals of the surgically treated group improved significantly (P = 0.0122) more than did those of the medically treated group but after treatment, significant differences in neurologic status were not evident between surgically (6.67 +/- 1.49) and medically (7.07 +/- 1.24) treated animals. Medically treated animals required substantially longer to reach optimal neurologic status, but the average hospital stay was nearly twice as long for the surgically treated animals (13.5 days), compared with those treated medically (7.1 days). Animals with thoracic vertebral fractures had mean neurologic status that was worse than that in animals with cervical vertebral fractures (P = 0.0109). After either medical or surgical treatment, neurologic status did not differ among animals with cervical, thoracic, or lumbar vertebral fractures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874678 TI - Cryptosporidiosis in neonatal calves: 277 cases (1986-1987). AB - From January 1986 through December 1987, 277 cases of cryptosporidiosis in calves were diagnosed by the South Dakota State University Diagnostic Laboratory. Cryptosporidium sp was the only pathogen identified in 142 (51.3%) of the calves. Concurrent infections with rotavirus, coronavirus, Escherichia coli, Salmonella sp, bovine viral diarrhea virus, or other pathogens were identified in the remaining 135 calves. After elimination of cases involving autolyzed specimens or calves with chronic diarrhea, records of 11 calves with acute, severe cryptosporidiosis were identified in which Cryptosporidium sp was the only pathogen. PMID- 1874679 TI - Implementation and evaluation of a strategic parasite control program for captive exotic ungulates. AB - A parasite control program was designed for greater than 1,200 exotic ungulates maintained in mixed-species enclosures at the San Diego Wild Animal Park. Three strategically-timed anthelmintic treatments were given during 1988-1989, and their success was evaluated by monitoring pretreatment and posttreatment fecal egg counts. Adequate parasite control was achieved for animals in 52 ungulate species, as evidenced by low pretreatment egg counts and the absence of egg shedding after treatment. However, animals belonging to 11 species in the subfamilies Antilopinae, Hippotraginae, and Caprinae were identified as important targets for more intensive control efforts because they shed either greater than 100 eggs/g of feces before treatment, or greater than 0 eggs/g after treatment, at 2 or more sampling periods. These results and observations were used to generate management recommendations and illustrate how a model parasite control program can be developed for collections of exotic ungulates. PMID- 1874680 TI - Method for transilial bone biopsy in baboons. AB - A surgical method for obtaining transilial bone biopsy specimens in baboons that provides adequate amounts of trabecular and cortical bone for histomorphometric analysis was developed. Biopsy specimens were removed from a site on the craniodorsal portion of the ilium by use of an 8-mm trephine. PMID- 1874681 TI - Factors involved in the balancing of equine hooves. PMID- 1874682 TI - What is your diagnosis? Upper airway obstruction in a horse caused by pharyngeal perforation during nasogastric intubation. PMID- 1874683 TI - Yeast spoilage of bakery products and ingredients. PMID- 1874684 TI - A rapid fluorogenic method for the detection of Escherichia coli by the production of beta-glucuronidase. AB - A medium containing the fluorogenic substrate 4-methylumbelliferyl-beta-D glucuronide was developed for the isolation and identification of Escherichia coli within 7.5 h and was based on the detection of beta-glucuronidase. Optimum conditions for the rapid development of fluorescent colonies were determined. The optimum temperature was 41.5 degrees C. Development of fluorescence was delayed when carbohydrates were incorporated into the medium. Water samples were used to evaluate the medium by surface plating and membrane filtration. The frequency of false-negative results was 6.1% and false-positives were 3.7% for freshwater samples. The false-positive organisms were identified as Klebsiella spp. and Shigella sonnei. The potential applications of the medium are discussed. PMID- 1874685 TI - The influence of agricultural run-off on bacterial populations in a river. AB - The microbiological quality of the River Riato (Spain) was evaluated. The influence of cattle that roam free in the warm season was marked. The degree of faecal pollution in the river was higher than predicted from the river basin geographical characteristics. The counts of faecal indicators greatly increased when the cattle were allowed to roam free. Counts of enterobacteria and faecal coliforms ranged from 10(3) to 10(6)/100 ml. Faecal streptococci counts were smaller (less than 10/100 ml). Escherichia coli and Pseudomonas aeruginosa were isolated from all samples. Streptococcus bovis was also isolated but not Strep. faecalis. PMID- 1874686 TI - A guide to sensitivity testing. Report of the Working Party on Antibiotic Sensitivity Testing of the British Society for Antimicrobial Chemotherapy. PMID- 1874687 TI - State findings on pesticide residues in food--1988 and 1989. AB - Findings of pesticide and related chemical residues are presented for 27,065 samples of foods collected and analyzed in 10 state food laboratories over 1988 and 1989 (fiscal years (FY) 88 and 89). These laboratories conduct food regulatory programs compatible with national programs of the U.S. Food and Drug Administration. Of the findings, 6325 samples contained detectable levels of 1 or more pesticide analytes and 418 (or 1.5%) of the total number of samples were deemed to be of regulatory significance. PMID- 1874688 TI - Liquid chromatographic determination of clidinium bromide and clidinium bromide chlordiazepoxide hydrochloride combinations in capsules. AB - A specific liquid chromatographic method was developed for determination of clidinium bromide and clidinium bromide-chlordiazepoxide hydrochloride combinations in capsules. The procedure uses a Partisil 10 ODS-3 column and a mobile phase consisting of acetonitrile-0.3M ammonium phosphate (32 + 68) (pH = 4.3). The detection wavelength is 235 nm. Accuracy, reproducibility, and linearity were within accepted criteria. Four commercial samples of the single ingredient were tested; results compared favorably with the compendial method. Two commercial samples of the combination product were tested by the proposed method and results reported. The system was found to be free from any interferences from the 4 known related compounds of the 2 major components and is useful as a screening procedure for 7-chloro-1,3-dihydro-5-phenyl-2H-1,4 benzodiazepin-2-one-4-oxide, the principal degradation product of chlordiazepoxide hydrochloride. PMID- 1874689 TI - Turbidimetric assay for tetracyclines in feeds using a microtiter plate system. AB - The microtiter plate system for turbidimetric assay of chlortetracycline (CTC) and oxytetracycline (OTC) levels in feeds uses a 96 well microtiter plate, a multichannel pipette, and an ELISA reader to measure turbidity. Feeds are extracted for both tetracyclines using AOAC extraction systems. For CTC, the range of the standard curve is 0.001-0.005 microgram CTC/mL; for OTC, the range is 0.004-0.016 microgram OTC/mL. Repeatability of CTC assays, as shown by the coefficient of variation (CV), ranged from 0.54 to 5.65% for same-day assays and from 2.01 to 9.39% for assays on different days. For OTC, CVs ranged from 2.69 to 10.01% for same-day assays and 3.24 to 9.08% for different-day assays. Average recoveries for CTC were 108.7% for same-day assays and 106.8% for different-day assays; for OTC, average recoveries were 112.4% and 106.5% for same-day and different-day assays, respectively. PMID- 1874690 TI - Capillary gas chromatographic determination of cyclohexanone and 2-ethyl-1 hexanol leached from solution administration sets. AB - A capillary gas chromatographic method is described for the determination of cyclohexanone and 2-ethyl-1-hexanol leached from solution administration sets. A preliminary study was made of compounds leached from solution administration sets by 5% sodium bicarbonate solution (pH 8.1), 0.9% sodium chloride solution (pH 6.8), and water. Water was selected as the leaching solvent because similar quantities of the compounds were leached into water and into both types of parenteral solutions. The correlation coefficients were 0.99977 for cyclohexanone and 0.99974 for 2-ethyl-1-hexanol, and recoveries were good (93-94%). Five administration sets from each of 2 manufacturers were analyzed by this method. The amounts of cyclohexanone that were leached from the individual sets varied considerably; however, similar quantities were leached from sets of both manufacturers. 2-Ethyl-1-hexanol was also found in extracts from each of the sets analyzed. PMID- 1874691 TI - Quantitation and confirmation of sulfamethazine residues in swine muscle and liver by LC and GC/MS. AB - The present paper describes a liquid chromatographic (LC) method for purification of crude swine tissue extracts before gas chromatographic/mass spectrometric (GC/MS) quantitation and confirmation of sulfamethazine at low ppb levels. Fractions corresponding to sulfamethazine were collected, evaporated to dryness, N-methylated with diazomethane, concentrated, and analyzed by GC/MS. A mass spectrometer was set to selected ion monitoring (SIM) mode. Ions 233, 227, 228, and 92 m/z were detected. Ratio 227/233 m/z (sulfamethazine/internal standard, [phenyl 13C6] sulfamethazine) was used for quantitation, while ratios 228/227 and 92/227 m/z, respectively, were used for confirmation. Quantitation in spiked blank muscle tissue was tested from 100 to 1 ppb and found acceptable at all concentrations studied; coefficients of variations ranged from 4.9 to 14.4%. Similar results were obtained for liver tissue from 5 to 20 ppb; coefficients of variation ranged from 1.2 to 9.1%. PMID- 1874692 TI - Liquid chromatographic determination of chloramphenicol in calf tissues: studies of stability in muscle, kidney, and liver. AB - A liquid chromatographic method has been developed for the measurement of chloramphenicol (CAP) in muscle, liver, and kidney. The mean recovery levels were 82.6, 75.3, and 79.2% in muscle, liver, and kidney, respectively. The method was repeatable and reproducible for CAP measurement in muscle, with a detection limit of 1 microgram/kg. Investigation of CAP stability in muscle, liver, and kidney showed that CAP stability in muscle was good at -20 degrees C; for spiked liver and kidney, degradation of CAP was observed, and the use of piperonyl butoxide (PB) for metabolism inhibition was recommended for recovery and linearity studies. However, PB was unnecessary for preservation of treated animal tissues if samples were cut into cubes and cooled at -20 degrees C, just after slaughter, pending analysis. With these limitations, CAP can be measured in liver and kidney. PMID- 1874693 TI - Liquid chromatographic method for multiresidue determination of benzimidazoles in beef liver and muscle: collaborative study. AB - A liquid chromatographic method for determination of thiabendazole, 5 hydroxythiabendazole, oxfendazole, mebendazole (MBZ), and fenbendazole (FBZ) in cattle liver and muscle was collaboratively studied in 7 laboratories in 1986. For blind fortified samples containing 800 ppb FBZ, average recovery and relative standard deviations for repeatability and reproducibility (RSDr and RSDR) based on results from 6 of the participating laboratories were 83%, 12.7%, and 14.0%, respectively. Recoveries of FBZ from incurred liver samples were more variable. Recoveries of MBZ from livers fortified at the 100 ppb level were encouraging; however, the drug levels were too low in the incurred samples used for MBZ studies. Except for FBZ and MBZ in liver, the study data were not satisfactory. The method has been adopted official first action by AOAC for determination of 800-1600 ppb fenbendazole in liver. The analysis should be repeated using a smaller sample size when initial analyses show levels greater than 1600 ppb FBZ. PMID- 1874694 TI - Matrix solid phase dispersion (MSPD) extraction and gas chromatographic screening of nine chlorinated pesticides in beef fat. AB - A multiresidue technique is presented for the extraction and quantitative gas chromatographic screening of 9 insecticides (lindane, heptachlor, aldrin, heptachlor epoxide, p,p'-DDE, dieldrin, endrin, p,p'-TDE, and p,p'-DDT) as residues in beef fat. Beef fat was fortified by adding the 9 insecticides, plus dibutyl chlorendate as internal standard, to 0.5 g portions of beef fat and blending with 2 g C18 (octadecylsilyl)-derivatized silica. The C18/fat matrix blend was fashioned into a column by adding the blend to a 10 mL syringe barrel containing 2 g activated Florisil. The insecticides were then eluted from the column with 8 mL acetonitrile, and a 2 microL portion of the acetonitrile eluate was then directly analyzed by gas chromatography with electron capture detection. Unfortified blank controls were treated similarly. The acetonitrile eluate contained all of the pesticide analytes (31.25-500 ng/g) and was free of interfering co-extractants. Correlation coefficients for the 9 extracted pesticide standard curves (linear regression analysis, n = 5) ranged from 0.9969 (+/- 0.0021) to 0.9999 (+/- 0.0001). Average relative percentage recoveries (85 +/- 3.4% to 102 +/- 5.0%, n = 25 for each insecticide), inter-assay variability (6.0 +/- 1.0% to 14.0 +/- 6.7%, n = 25 for each insecticide), and intra-assay variability (2.5-5.1% n = 5 for each insecticide) indicated that the methodology is acceptable for the extraction, determination, and screening of these residues in beef fat. PMID- 1874695 TI - Enzyme immunoassay for hen egg white lysozyme used as a food additive. AB - An indirect competitive enzyme immunoassay for hen egg white lysozyme (HEL) used as a food additive was investigated. Anti-HEL antibodies were obtained from B10A mouse ascites immunized by intraperitoneal injection of HEL. HEL samples to be assayed were extracted from foods with 1% gelatin in borate buffer. Goat anti mouse IgG (H+L)-peroxidase complex was used as a second antibody, and 3,3',5,5' tetramethylbenzidine was used as a substrate for the peroxidase. The working range for quantitative analysis was 1-50 ng/mL, because in this range the binding inhibition curve of anti-HEL antibodies to HEL-coated plates by HEL was linear. Even after losing the lysozyme activity by heat treatment, HEL could be detected by indirect competitive enzyme immunoassay. Recoveries of HEL by this assay were greater than 85% for Japanese noodles and Japanese traditional-style confectioneries, 53-95% for Miso and cooked beans, and 30-85% for fried fish pastes. HEL contents of 55 commercial foods were determined; HEL was detected in 19 samples in the range 25-20,000 ng/g. HEL as a food additive was detected more frequently in plant-derived foods than in foods of animal origin. PMID- 1874696 TI - Determination of food contamination by mineral oil from jute sacks using coupled LC-GC. AB - Jute fibers are treated with about 5-7% of a high boiling mineral oil fraction ("batching oil") to render them flexible for making fabrics. Foods transported in jute bags are contaminated by this batching oil. A method involving automated on line LC-GC is described for determining these hydrocarbons in various foods. Complete transfer of the LC fraction to GC is presupposed for obtaining the required sensitivity. Results are given for nuts, coffee, cocoa products, and rice. Contamination ranged between about 5 and 500 ppm. PMID- 1874697 TI - Quantitative analysis of limonin in grapefruit juice using an enzyme-linked immunoassay: interlaboratory study. AB - Eleven laboratories participated in an interlaboratory study of an enzyme-linked immunoassay for limonin in grapefruit juice. Participating laboratories received training and practice samples until familiar with the procedure. Laboratories then received 8 sample pairs of grapefruit juice as blind duplicates. Samples were refrigerated and analyzed within 4 days of receipt. Results from 1 laboratory and 6 individual samples were excluded from the statistical analysis. Method performance was measured by the one-way component of variance analysis. Repeatability relative standard deviations (RSDr) ranged from 7.0 to 15.6%. Reproducibility relative standard deviations (RSDR) ranged from 12.9 to 29.4%. PMID- 1874698 TI - Continuous flow vapor generation for inductively coupled argon plasma spectrometric analysis. Part 2. Arsenic. AB - Total arsenic is determined by inductively coupled plasma atomic emission using hydride vapor generation. A 1 g sample is wet washed in a 16 x 150 mm 10 mL volumetric test tube on a programmed heating block with nitric, sulfuric, and perchloric acids at up to 310 degrees C. After treatment with hydrochloric acid and potassium iodide, arsenic is reduced by sodium borohydride to arsine in a simplified continuous flow manifold. A standard pneumatic nebulizer affects the gas-liquid separation of AsH3, which is quantified by ICP atomic emission at 193.756 nm. The instrument detection limit for the method has been determined to be 0.4 microgram/L. For a 10:1 dilution of a nominal 1 g sample, the detection limit is 4 micrograms/kg and the linear range is up to 4 mg/kg. Recoveries from 3 matrixes were 99-104%, with a typical RSD of 2%. The method has demonstrated statistical control for samples of biological interest and is especially well suited to analysis of small samples. PMID- 1874699 TI - Defined substrate technology method for rapid and specific simultaneous enumeration of total coliforms and Escherichia coli from water: collaborative study. AB - The defined substrate technology (DST) method is a reagent system designed to enumerate specific target microbes(s) from a mixture of bacteria. The system simultaneously enumerates total coliforms and Escherichia coli directly from a water sample. The reagent contains o-nitrophenyl-beta-D-galactopyranoside (ONPG), which is hydrolyzed by total coliforms to produce a yellow chromogen, and 4 methylumbeilliferyl-beta-D-glucuronide (MUG), which is hydrolyzed and fluoresces when E. coli organisms grow. Noncoliform bacteria are suppressed and cannot metabolize the indicator nutrients. Nine laboratories participated in a field evaluation of the method, which covered a wide range of surface and subsurface water sources and water-processing modalities, including the examination of natural samples. The DST system was compared to multiple-tube fermentation (MTF) (quantitative) and presence-absence (P-A) (qualitative) Standard Methods formats. Comparison of water samples from natural sources by using the most probable number (MPN) procedure showed that the DST test was equivalent to the currently used MTF test. Results from the DST and the qualitative P-A procedure showed that these tests agreed with each other in 94% of the water samples analyzed. Specificity of the DST method was established by subculturing a species consistent with a total coliform or E. coli from each positive tube. Eight laboratories participated in a collaborative study of the method. Each laboratory received 3 concentrations of E. coli (organisms/100 mL); 10 (low); 60 (medium); and 120 (high). The DST test was inoculated from a split sample of each bacterial density in parallel with Standard Methods brilliant green lactose broth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874700 TI - Determination of monocyclic and polycyclic aromatic hydrocarbons in fish tissue. AB - An analytical method is presented in which fish tissue is analyzed for neutral monocyclic and polycyclic aromatic hydrocarbons (AHs) and aromatic sulfur heterocycles (ASHs) by capillary column gas chromatography (CGC) with photoionization detection. The sample enrichment procedure includes saponification with aqueous KOH, acidification of the digestates, and extraction of the aromatic compounds into cyclopentane-dichloromethane. Adsorption chromatography on tandem segments of potassium silicate and silica gel removes 99% of the coextracted lipid. Final enrichment by gel permeation chromatography eliminates residual biogenic material and potentially interfering alkanes. Relatively volatile monoaromatics are included among the analytes by virtue of the efficiency of the complementary enrichment steps, the use of small quantities of only low-boiling solvents, and the selectivity of the detector. Most targeted compounds (AHs ranging in size from C3-alkylbenzenes through benzo[g,h,l]perylene and ASHs within the same size range) can be determined in 5 g (wet weight) samples of fish tissue at concentrations as low as 20 ng/g. Comparisons are made of recoveries of selected AHs under ordinary and gold fluorescent lighting conditions. PMID- 1874701 TI - Zinc chloride-diphenylamine reagent for thin layer chromatographic detection of some organophosphorus and carbamate insecticides. AB - Zinc chloride-diphenylamine reagent, whose use has been reported for the detection of organochlorine insecticides by thin layer chromatography, was further studied for its ability to detect the organophosphorus insecticides phorate, phosphamidon, DDVP, and phosalone and the carbamate insecticide carbaryl and aldicarb. These insecticides give intense blue-green spots with this reagent. The procedure can be applied to the detection of the insecticides in biological materials and thus has a potential use in forensic toxicology. PMID- 1874702 TI - Determination of oxyfluorfen herbicide and oxyfluorfen amine residues in garbanzo beans by liquid chromatography. AB - Oxyfluorfen and oxyfluorfen amine were determined by liquid chromatography (LC) with ultraviolet (UV) and photoconductivity detection (PCD). A simple extraction procedure acceptably recovered both analytes from garbanzo beans over a wide range of fortifications (0.05 to 20 ppm) (83 +/- 4 for oxyfluorfen; 85 +/- 4 for oxyfluorfen amine). Percent recoveries decreased slightly as the fortification level decreased. Both analytes could be determined simultaneously at a concentration greater than 0.2 ppm in garbanzo beans. Detection limits were 3 ng for oxyfluorfen and 100 ng for oxyfluorfen amine using LC/UV, and 12 ng for both oxyfluorfen and oxyfluorfen amine with LC/PCD. Different knitted reaction coils and photoreactors were evaluated. Photoproduct yields and identification were determined by ion chromatography. The LC/PCD method measures oxyfluorfen and oxyfluorfen amine separately and has a shorter analysis time, while the standard method using gas chromatography measures total residues and is more sensitive. PMID- 1874703 TI - Multiresidue screening method for fresh fruits and vegetables with gas chromatographic/mass spectrometric detection. AB - A gas chromatographic/mass spectrometric (GC/MS) screening method has been developed for the determination of pesticide residues in a variety of crop samples. Samples are extracted with acetonitrile and partitioned with sodium chloride saturated aqueous solution. Targeted pesticide analytes are separated on a short, narrow bore capillary column, identified by electron ionization MS scanned from 100 to 400 amu, and quantitated by the monitoring of base ions and internal standards. The accuracy of the quantitative determination measured in terms of average percentage recovery of 143 compounds in 13 crop samples was 92% with a relative standard deviation of 22%. PMID- 1874704 TI - Comparison of microwave digestion with conventional wet ashing and dry ashing digestion for analysis of lead, cadmium, chromium, copper, and zinc in shellfish by flame atomic absorption spectroscopy. AB - A closed vessel microwave digestion procedure was developed for shellfish samples. This procedure was compared with wet and dry ash procedures for levels of lead, cadmium, chromium, copper, and zinc. Results obtained for microwave and conventional wet ash digestion were comparable. The dry ashing procedure produced results consistently lower than either of the other methods. Recoveries ranged from 80-92% for microwave and wet ashing procedures and 54-72% for the dry ashing procedure. Accuracy was also determined by analyzing lobster hepatopancreas marine reference material. Values for Pb, Cd, and Cr fell within the range specified for the reference material for all 3 digestion procedures; however, values were lower for Cu and Zn. Results of this study show that microwave digestion is comparable to wet ashing. PMID- 1874705 TI - Improved selenium recovery from tissue with modified sample decomposition. AB - The present paper describes a simple modification of a recently reported decomposition method for determination of selenium in biological tissue by hydride generation atomic absorption. The modified method yielded slightly higher selenium recoveries (3-4%) for selected reference tissues and fish tissue spiked with selenomethionine. Radiotracer experiments indicated that the addition of a small volume of hydrochloric acid to the wet digestate mixture reduced slight losses of selenium as the sample initially went to dryness before ashing. With the modified method, selenium spiked as selenomethionine behaved more like the selenium in reference tissues than did the inorganic spike forms when this digestion modification was used. PMID- 1874706 TI - The Visible Human Project. PMID- 1874707 TI - Collaborations in art/science: Renaissance teams. AB - A Renaissance Team is a group of specialists who collaborate and provide synergism in the quest for knowledge and information. Artists can participate in Renaissance Teams with scientists and computer specialists for scientific visualization projects. Some projects are described in which the author functioned as programmer and color expert, as interface designer, as visual paradigm maker, as animator, and as producer. Examples are provided for each of these five projects. PMID- 1874708 TI - Perception, cognition, and visualization. AB - Visualization refers to the cognitive functions of visual perception. In visualization, pictures combine aspects of naturalistic representation with more formal shapes to enhance cognitive understanding. These "diagrammatic" shapes derive from geometrical elements and thereby bestow visual concreteness to concepts conveyed by the pictures. Leonardo da Vinci's anatomical drawings survive as masterful prototypes exemplifying these traits. PMID- 1874709 TI - Computer-aided geometric modeling of the human eye and orbit. AB - The author advocates, as a long-term development agenda for the profession, a shift in the working methods of medical illustrators from a two-dimensional image processing mode to a computer-aided design and drafting (CADD) mode. Existing CADD technology, which can make short work of the complex graphic construction problems of anatomical visualization, performs virtually all of its manipulations through systematic exercise of graphic geometry which illustrators tend to reduce to an intuitive, almost vestigial supplement to 2D image processing methods. The primary barrier to the immediate use of CADD is a lack of geometric database materials on anatomical component systems of the body. An on-going experimental project in modeling the human eye and orbit, utilizing a Silicon Graphics Iris workstation and Control Data Corporation's Integrated Computerized Engineering and Manufacturing (ICEM) software, exemplifies the preparatory work needed to create such database materials. PMID- 1874710 TI - The Vesalius Project: interactive computers in anatomical instruction. AB - The goal of the Vesalius Project is a high-resolution, interactive 3-D atlas of human/animal anatomy, stored on a laser videodisc and displayed on graphics workstations--an an "electronic Gray's Anatomy." Students will use this computerized atlas interactively to learn the structure of the body and to understand their own bodies in health and disease. The Human Factors Research Laboratory at Colorado State University has designed and is conducting a comprehensive evaluation program for the project. PMID- 1874711 TI - Videodisc animation of 3D computer reconstructions of the human brain. AB - Our group is creating a database of x-, y-, z- coordinates of central nervous system structures from serial cross-sections. We produce 3D computer images of the brain and its components and record them on videodisc. Useful animations include combining objects from different databases to correct anatomical scale, rendering a surface translucent to reveal underlying components, slicing and paging brain slabs with and without protruding individual objects, and dissecting functional pathways. We are beginning to use videodisc animations of the nervous system in computer-based interactive tutorials. PMID- 1874712 TI - New dimensions: curriculum challenges. PMID- 1874713 TI - Enhancer element at the 3'-flanking region controls transcriptional response to hypoxia in the human erythropoietin gene. AB - Erythropoietin gene expression is greatly stimulated under conditions of hypoxia. The activation of the erythropoietin gene appears regulated primarily at the level of gene transcription. To study cis-acting elements involved in the response to hypoxia a mini-gene was constructed by an internal deletion from exon II to V of the human erythropoietin gene and used in transient transfection assays in the erythropoietin producing Hep 3B cell line. It was initially found that hypoxia responsiveness was present in an erythropoietin fragment containing 400 base pairs (bp) of 5'-flanking and 600 bp of 3'-flanking regions. Deletion analysis showed no significant effect on the response to hypoxia when highly conserved regions of 5'-flanking sequence, exon and intron I, and exon V were removed from the mini-gene construct. However, removal of a fragment containing the 3' end of the gene and 3'-flanking sequences completely eliminated hypoxia responsiveness. Reinsertion of the above fragment upstream of the 5' end of the mini-gene restored the response to hypoxia. Further analysis using hybrid erythropoietin-chloramphenicol-acetyltransferase constructs allowed the localization of enhancer-like element(s) in the 3'-flanking region, approximately 120 bp downstream of the polyadenylation site of the human erythropoietin gene. Activation by these sequences were position- and orientation-independent and stimulated 15-fold transcription of the erythropoietin gene in response to hypoxia. PMID- 1874714 TI - In vitro biosynthesis of [Thr2,Leu5,D-Hiv8,Leu10]-cyclosporin, a cyclosporin related peptolide, with immunosuppressive activity by a multienzyme polypeptide. AB - A new cyclic peptolide (SDZ 214-103), which is produced by the fungus Cylindrotrichumoligospermum (Corda) BONORDEN (Dreyfuss, M. M., Schreier, M. H., Tscherter, H., and Wenger, R. (June 15, 1988) European Patent Application 0 296 123 A2) and is closely related to cyclosporin A (CyA), has as the main structural difference D-2-hydroxyisovaleric acid in ester linkage at position 8 instead of D alanine in the cyclosporins. This peptolide exerts similar biological activities to CyA. We were able to prepare an enzyme fraction of crude extracts of the mycelium, which is capable of synthesizing the peptolide with consumption of the constitutive amino acids, D-2-hydroxyisovaleric acid, ATP, and S-adenosyl-L methionine. The in vitro product co-chromatographs with authentic peptolide on thin layer chromatography and high performance liquid chromatography and shows similar immunosuppressive activity in vitro. The enzyme does not synthesize CyA, whereas cyclosporin synthetase does not synthesize the peptolide. Peptolide synthetase has a high molecular weight (in the same range as cyclosporin synthetase) and also does not appear to be glycosylated. The enzyme cross-reacts with antibodies directed specifically against cyclosporin synthetase. PMID- 1874715 TI - Nonfarnesylated tetrapeptide inhibitors of protein farnesyltransferase. AB - The protein farnesyltransferase from rat brain was previously shown to be inhibited competitively by tetrapeptides that conform to the consensus Cys-A1-A2 X, where A1 and A2 are aliphatic amino acids and X is methionine, serine, or phenylalanine. In the current studies we use a thin layer chromatography assay to show that most of these tetrapeptides are themselves farnesylated by the purified enzyme. Two classes of tetrapeptides are not farnesylated and therefore act as true inhibitors: 1) those that contain an aromatic residue at the A2 position and 2) those that contain penicillamine (beta,beta-dimethylcysteine) in place of cysteine. The most potent of these pure inhibitors was Cys-Val-Phe-Met, which inhibited farnesyltransferase activity by 50% at less than 0.1 microM. These data indicate that the inclusion of bulky aromatic or methyl residues in a tetrapeptide can abolish prenyl group transfer without blocking binding to the enzyme. This information should be useful in the design of peptides or peptidomimetics that inhibit farnesylation and thus block the action of p21ras proteins in animal cells. PMID- 1874716 TI - Cleavage of cartilage proteoglycan between G1 and G2 domains by stromelysins. AB - Normal and pathological turnover of proteoglycans in articular cartilage involves its cleavage close to the N-terminal G1 domain responsible for aggregation. A fragment containing G1 and G2 N-terminal domains of pig cartilage proteoglycans was therefore used as a substrate to investigate its degradation by the metalloproteinase stromelysin and related recombinant stromelysin enzymes. The stromelysins produced an apparent single cleavage yielding a G1 fragment of 56 kDa and a G2 fragment of 110 kDa. Rabbit bone stromelysin was much more active against the G1-G2 fragment and against proteoglycan aggregates than recombinant human stromelysin-1 and stromelysin-2. All metalloproteinase preparations were active against proteoglycan and the G1-G2 fragment at acid (pH 5.5) and neutral pH (7.4). N-terminal sequencing of the G2 fragment derived from the action of recombinant human stromelysin-1 revealed that cleavage between G1 and G2 occurred at the N-terminal end of the interglobular domain, close to the last cysteine in G1. The specific cleavage site was between an asparagine and a pair of phenylalanine residues, where the asparagine corresponds to residue 341 in human and rat mature core protein sequence. PMID- 1874717 TI - Dissociative inhibition of dimeric enzymes. Kinetic characterization of the inhibition of HIV-1 protease by its COOH-terminal tetrapeptide. AB - Human immunodeficiency virus 1 (HIV-1) protease is an aspartyl protease composed of two identical protomers linked by a four-stranded antiparallel beta-sheet consisting of the NH2- and COOH-terminal segments (Weber, I.T. (1990) J. Biol. Chem. 265, 10492-10496). Kinetic analysis of the HIV-1 protease-catalyzed hydrolysis of a fluorogenic substrate demonstrates that the enzyme is an obligatory dimer. At pH = 5.0, 0.1 M sodium acetate, 1 M NaCl, 1 mM EDTA buffer, 37 degrees C, the equilibrium dissociation constant, Kd = 3.6 +/- 1.9 nM. We found that the tetrapeptide Ac-Thr-Leu-Asn-Phe-COOH, corresponding to the COOH terminal segment of the enzyme, is an excellent inhibitor of the enzyme. Kinetic analysis shows that the inhibitor binds to the inactive protomers and prevents their association into the active dimer (dissociative inhibition). The dissociative nature of this inhibition is consistent with the results obtained from sedimentation equilibrium experiments in which the apparent molecular weight of the enzyme was observed to be 20,800 +/- 1,500 and 12,100 +/- 300, in the absence and presence of the COOH-terminal tetrapeptide, respectively. The dissociation constant of the protomer-inhibitor complex is Ki = 45.1 +/- 1.8 microM. This is the first kinetic analysis and direct experimental demonstration of noncovalent dissociative inhibition. PMID- 1874718 TI - Polarized regulation of fibronectin secretion and alternative splicing by transforming growth factor. AB - Fibronectin is a multifunctional protein that is synthesized in several different forms that result from alternative splicing of mRNA. Although expression of splicing variants appears to be both developmentally regulated and tissue specific, the functional significance of these isoforms is largely unknown. We found that cultured airway epithelial cells vectorially secrete two distinct species of fibronectin, one which contains the alternatively spliced EIIIA region (EIIIA+) and one in which the EIIIA segment is spliced out (EIIIA-). Fibronectin containing the EIIIA region is preferentially secreted apically. Although both apical and basal stimulation with transforming growth factor beta 1 increased fibronectin synthesis, the secretory response differed depending on which surface was being stimulated. Apical secretion of fibronectin and expression of EIIIA+ fibronectin mRNA increased only after apical stimulation. These data demonstrate a novel mechanism for the polarized regulation of targeted secretion and alternative splicing of fibronectin and suggest that the EIIIA segment may act as a targeting signal for the vectorial secretion of fibronectin. PMID- 1874719 TI - Substitutions for glycine alpha 1-637 and glycine alpha 2-694 of type I procollagen in lethal osteogenesis imperfecta. The conformational strain on the triple helix introduced by a glycine substitution can be transmitted along the helix. AB - Two substitutions for glycine in the triple-helical domain were found in type I procollagen synthesized by skin fibroblasts from two probands with lethal osteogenesis imperfecta. One was a substitution of valine for glycine alpha 1 637, and the other was a substitution of arginine for glycine alpha 2-694. The effects of the mutations on the zipper-like folding of the collagen triple helix were similar, since there was post-translational overmodification of the collagenase A fragments (amino acids 1-775) but not of more COOH-terminal fragments of the protein. The mutations differed markedly, however, on their effects on thermal unfolding of the triple helix. The collagenase A fragment from the collagen containing the arginine alpha 2-694 substitution was cleaved at about amino acid 700 when incubated with trypsin at 30-35 degrees C. Therefore, there was micro-unfolding of the triple helix at a site close to the glycine substitution. Surprisingly, however, the collagenase A fragment with the valine alpha 1-637 substitution was also cleaved at about amino acid 700 under the same conditions. The results, therefore, demonstrated that although most glycine substitutions delay folding of the triple helix in regions that are NH2-terminal to the site of the substitution, the effects on unfolding can be transmitted to regions that are COOH-terminal to the site of the glycine substitution. PMID- 1874720 TI - Erythropoietin enhances the assembly of alpha,beta spectrin heterodimers on the murine erythroblast membranes by increasing beta spectrin synthesis. AB - Previous biosynthetic studies have revealed that in both mammalian and chicken erythroid cells, alpha spectrin is synthesized in 2-3-fold excess over beta spectrin. However, in the membrane skeleton, the two polypeptides are assembled in equimolar amounts, suggesting that the association of alpha spectrin with the membrane skeleton is rate-limited by the amount of beta spectrin synthesized. Here we have analyzed the synthesis and transcription of alpha and beta spectrin in Friend virus-infected murine erythroblasts (FVA cells) in vitro during the erythropoietin-dependent period of maturation. Erythropoietin (Epo) increases the synthesis of beta spectrin but not alpha spectrin, thereby altering the alpha/beta spectrin synthetic ratio. When immature FVA cells are exposed for 24 h to a standard dose of 0.2 unit/ml Epo for maximum effect, the mRNA content and the synthesis of beta spectrin are increased resulting in about 1.3-1.5-fold excess of beta spectrin over alpha spectrin in the cytosol. On the membrane, the incorporation of both alpha and beta spectrins is increased equally by about 30 35%. Furthermore, nuclear run-off transcription measurements indicate that the increased beta spectrin gene expression is regulated at the level of transcription. We conclude that in cells with strong Epo stimulus, the expression and synthesis of beta spectrin are increased resulting in an increase in the amount of alpha,beta spectrin heterodimers available for membrane assembly. PMID- 1874721 TI - Isoform diversity of phosphorylase kinase alpha and beta subunits generated by alternative RNA splicing. AB - We have sequenced rabbit cDNAs that encode one isoform of the alpha subunit and two isoforms of the beta subunit of phosphorylase kinase, in addition to the single isoform from fast skeletal muscle that has been characterized to date for each subunit. All these isoforms are generated by alternative RNA splicing. The alpha subunit sequence obtained from slow skeletal muscle (soleus) is characterized by an internal deletion of 59 amino acids. This deletion is predominant in mRNA from slow muscle, heart, and uterus and accounts for the smaller alpha subunit variant (alpha') characteristic of phosphorylase kinase purified from slow muscle and heart. The beta subunit mRNA can be differentially spliced at two sites. In all tissues (except skeletal muscle) that were analyzed, an internal segment encoding 28 amino acids of the muscle sequence is replaced by a homologous sequence of identical length, presumably through the use of mutually exclusive exons. In brain and some other tissues, the deduced N-terminal sequence of the beta subunit is also changed. This is achieved by an insertion into the mRNA sequence that interrupts the initial reading frame after 25 codons and starts a new reading frame, encoding a different N terminus of 18 amino acids. This modification probably affects the major regulatory phosphorylation site of the beta subunit. PMID- 1874722 TI - Long-range effects and conformational flexibility of aldolase. AB - The conformational flexibility and long-range interactions in rabbit muscle aldolase induced by active-site ligand binding, cross-linking of the enzyme between Cys72 and Cys338, and removal of the C-terminal tyrosine residue were studied by following the changes in the microenvironments of Cys239 and Cys289 located outside the active site. It was found that substrates induced a conformational change in aldolase, which propagates from the active site to Cys239, which is located close to intersubunit contacts. The response of the enzyme is differential. Ligands having both C-1 and C-6 phosphates or C-1 phosphate only induce the enhancement of Cys239 reactivity, whereas those with C 6 phosphates only decrease Cys239 reactivity. This correlates well with a dramatic difference in kinetic parameters for a cleavage of fructose-1,6-P2 and fructose-1-P. Therefore, these changes can be interpreted as syncatalytic. Cross linking of the aldolase subunit by an -S-S-bridge between Cys72 and Cys338 inactivates the enzyme, abolishes binding of active-site ligands, and induces a conformational change in the enzyme that can be detected far away (at Cys239 and Cys289) from the site of perturbation. Cys72 and Cys338 are not in the active site. This shows that the region of the active site and the environment of Cys72 and Cys338 are tightly coupled and that residues far away from the active site, through such coupling, can possess properties of active-site residues. Similar, although less dramatic changes are observed upon removal of the C-terminal tyrosine residue. In view of the results obtained in this paper, aldolase seems to be quite a flexible molecule, whose conformation is sensitive to the nature of a substrate bound to the enzyme and is able to transmit the information about a local perturbation over long distances within a molecule. PMID- 1874723 TI - Proteolytic processing of the insulin receptor beta subunit is associated with insulin-induced receptor down-regulation. AB - This report describes the use of an antibody directed against the carboxyl terminus of the insulin receptor beta subunit to assess the fate of the insulin receptor protein over the time course of insulin-induced receptor down regulation. The insulin receptor beta subunit is lost from the cellular membranes of insulin-treated 3T3-C2 fibroblasts with a time course superimposable with the insulin-induced loss of cellular insulin binding activity. Concomitant with the time-dependent loss of the intact beta subunit from the membranes, a 61,000-Da fragment of the insulin receptor beta subunit accumulates in the cytosol of the cells in a time-dependent manner. The insulin-induced loss of the intact beta subunit from the cellular membranes is inhibited by cycloheximide. Chloroquine and the thiol protease inhibitors leupeptin and E-64 inhibit the insulin-induced loss of the intact beta subunit from the membranes and induce an accumulation of the intact subunit in the membranes. However, in the presence of leupeptin, E-64, or chloroquine, the insulin-induced loss of insulin binding activity occurs normally. These data indicate that down-regulation results in the loss of the intact beta subunit from the cellular membranes with the production of a fragment of the beta subunit in the cytosol. The protease responsible for the generation of the fragment is a thiol protease which requires acidic conditions. Since the insulin-induced proteolysis of the beta subunit can be totally inhibited under conditions where the insulin-induced loss of insulin binding activity proceeds normally, the proteolysis of the beta subunit is a process which is separate and distinguishable from the insulin-induced loss of insulin binding activity. PMID- 1874724 TI - Mechanism of activation of protein synthesis initiation in mitogen-stimulated T lymphocytes. AB - The pronounced stimulation of protein synthesis in T lymphocytes in response to mitogens is partly due to increased cell size and hence ribosome number. There is also a large increase in translation rate per ribosome as a result of an increased rate of initiation. In response to mitogen, levels of both eukaryotic initiation factor (eIF)-2 and guanine nucleotide exchange factor, GEF, increase in parallel with ribosomes which is consistent with a general increase in the translational machinery but cannot explain the increase in activity per ribosome. However, as total eIF-2 accumulates, the ratio of phosphorylated eIF-2 alpha (eIF 2(alpha P] to eIF-2 alpha decreases. Further, the levels of eIF-2(alpha P) and GEF in resting T lymphocytes are similar. As eIF-2(alpha P) inhibits GEF by effectively sequestering the exchange factor in an inactive 1:1 complex, the level of GEF available for protein synthesis initiation must be very low in resting cells. Hence, as GEF is synthesized and rises above the level of eIF 2(alpha P), there will be a disproportionate increase in GEF available for initiation compared with the increase in total GEF. This increase in available GEF is probably great enough to support the increase in translation rate per ribosome as well as the increase in ribosome number. PMID- 1874725 TI - Identification of kex2-related proteases in chromaffin granules by partial amino acid sequence analysis. AB - We have characterized glycoprotein H (GpH) from bovine adrenal medullary chromaffin granules. Two-dimensional gel electrophoresis was used to purify GpH from an insoluble fraction obtained following extraction of chromaffin granule membranes with lithium diiodosalicylate. The GpH material was recovered from two dimensional gel spots by concentration and recovery on a one-dimensional gel followed by electro-blotting to a poly(vinylidene difluoride) membrane. This material was subjected to in situ tryptic digestion. The released peptides were purified by microbore high performance liquid chromatography and sequenced. The peptide sequences revealed extensive similarity to the mammalian kex2/subtilisin related proteases (PC2 and PC3) which have been characterized recently by molecular cloning and sequence analysis (Smeekens, S. P., and Steiner, D. F. (1990) J. Biol. Chem. 265, 2997-3000; Smeekens, S. P., Avruch, A. S., LaMendola, J., Chan, S. J., and Steiner, D. F. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 340 344). The sequence similarity included regions that contain residues equivalent to the aspartic acid and histidine residues which are involved in the active site of the subtilisin family of serine proteases. The sequence data revealed the presence of tryptic peptides derived from both PC2 and PC3. NH2-terminal sequence analysis of GpH gave two sequences which were aligned with residues 110-121 of PC2 and PC3. It is likely that these sequences represent the mature form of PC2 and PC3 in chromaffin granules. These forms would be generated by cleavage at a site which is conserved in mammalian kex2-related enzymes and which would result in the release of approximately 80-residue propeptides. It was concluded that the spot identified as GpH by two-dimensional gel electrophoresis contains the bovine counterparts of both PC2 and PC3. The direct identification of these components in chromaffin granules supports their role in the processing of protein precursors. PMID- 1874726 TI - Studies of L-canavanine incorporation into insectan lysozyme. AB - L-Canavanine is incorporated into the lysozyme synthesized, in response to administration of bacterial cell wall materials, by canavanine-treated larvae of the tobacco hornworm Manduca sexta (Sphingidae). Maximum canavanine incorporation into M. sexta lysozyme occurs when the larvae are provided 1 mg of canavanine g-1 fresh body weight. Analysis of canavanine-containing lysozyme purified from these insects reveals that 21% of the arginine residues are replaced by canavanine; this residue substitution results in a loss of 49.5% of the catalytic activity. When the larvae are provided 0.5 mg of canavanine g-1, 16.5% of the arginine residues are substituted by canavanine and 39.5% of the catalytic activity is lost. Canavanine is also incorporated into the lysozyme induced by canavanine treated pupae of the giant silk moth Hyalophora cecropia (Saturnidae). In contrast, replacement of 17% of the arginine in H. cecropia lysozyme by canavanine fails to affect the catalytic activity. We have determined the primary structure of M. sexta lysozyme and compared it with the primary structure of H. cecropia lysozyme which has been described elsewhere. M. sexta lysozyme has an arginine at positions 23, 42, and 107. H. cecropia contains serine, lysine, and lysine, respectively, at these locations. The ability of incorporated canavanine to inhibit M. sexta lysozyme activity selectively may result from the fact that replacement of any one of the 3 arginine residues at position 23, 42, or 107 by canavanine causes the loss of catalytic activity. PMID- 1874727 TI - Characterization of purified, reconstituted site-directed cysteine mutants of the lactose permease of Escherichia coli. AB - lac permease mutated at each of the 8 cysteinyl residues in the molecule was solubilized from the membrane, purified, and reconstituted into proteoliposomes. The transport activity of proteoliposomes reconstituted with each mutant permease relative to the wild-type is virtually identical with that reported for intact cells and/or right-side-out membrane vesicles. Moreover, a double mutant containing Ser in place of both Cys148 and Cys154 exhibits significant ability to catalyze active lactose transport. The results provide strong confirmation for the contention that cysteinyl residues in lac permease do not play an important role in the transport mechanism. The effect of sulfhydryl oxidant 5-hydroxy-2 methyl-1,4-naphthoquinone on lactose transport in proteoliposomes reconstituted with wild-type or mutant permeases was also investigated, and the results indicate that inactivation is probably due to formation of a covalent adduct with Cys148 and/or Cys154 rather than disulfide formation. Thus, it seems unlikely that sulfhydryl-disulfide interconversion functions to regulate permease activity. PMID- 1874729 TI - Immunoaffinity-purified DNA polymerase alpha from a mouse temperature-sensitive mutant, tsFT20 strain, is heat-labile. AB - We have purified DNA polymerase alpha from a temperature-sensitive mutant cell line of mouse FM3A cells, tsFT20, that shows temperature-sensitive activity of DNA polymerase alpha (Murakami, Y., Yasuda, H., Miyazawa, H., Hanaoka, F., and Yamada, M. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 1761-1765). The purified enzyme was composed of two polypeptides with the same apparent molecular weights as those of purified DNA polymerase alpha from the parental strain, FM3A (Mr 180,000 and 68,000). Heat inactivation experiments revealed that this purified DNA polymerase alpha from tsFT20 cells was more heat-labile than the wild-type enzyme. We have also purified primase from both ts-FT20 cells and wild-type cells. Both primase fractions consist of two polypeptides with molecular weights of 54,000 and 46,000. No difference was observed between the heat labilities of the primases from tsFT20 cells and wild-type cells. Comparisons of wild-type and mutant polymerase indicated that the temperature-sensitive mutation in DNA polymerase alpha from tsFT20 cells affect the dCTP-binding site of the enzyme. The mutation also changed the optimum pH and the optimum KCl concentration of the enzyme. PMID- 1874728 TI - Cloning and expression in Escherichia coli of a human cDNA encoding the DNA repair protein N-methylpurine-DNA glycosylase. AB - A 871-base pair cDNA encoding the human N-methylpurine-DNA glycosylase (MPG) was cloned from a HeLa S3 cDNA expression library in a pUC vector by phenotypic screening of MPG-negative (tag- alkA-) Escherichia coli cells exposed to methylmethane sulfonate. The active MPG is expressed as a 31-kDa fusion protein. The human cDNA-encoded MPG releases 3-methyladenine, 7-methylguanine, and 3 methylguanine from DNA and thus has a substrate range similar to that of the indigenous enzyme and the E. coli AlkA protein. The cDNA hybridizes with distinct restriction fragments of mammalian DNAs but not with E. coli or yeast DNA. A search in the GenBank data bank failed to show any other cloned DNA with a similar sequence. Although the human protein has 62% sequence homology with the corresponding rat enzyme, only a few amino acid residues are conserved between the human protein and the E. coli and yeast MPGs. However, a conserved glutamine residue in all MPGs that release 3-alkyladenine and an arginine residue in eukaryotic MPGs and E. coli AlkA that act additionally on N-alkylguanines suggest that these residues are involved in recognition of adenine and guanine adducts in DNA, respectively. Although the 1.1-kilobase mRNAs of MPG from human and rodents are similar in size, liver and cultured cells of rat have much lower levels of MPG mRNA than do human and mouse cells. A hamster cell line variant isolated as being resistant to methylmethane sulfonate does not have a higher level of MPG mRNA than the parent cell line. PMID- 1874730 TI - Characterization of factor VII association with tissue factor in solution. High and low affinity calcium binding sites in factor VII contribute to functionally distinct interactions. AB - Protein-phospholipid as well as protein-protein interactions may be critical for tight binding of the serine protease factor VIIa (VIIa) to its receptor cofactor tissue factor (TF). To elucidate the role of protein-protein interactions, we analyzed the interaction of VII/VIIa with TF in the absence of phospholipid. Binding of VII occurred with similar affinity to solubilized and phospholipid reconstituted TF. Lack of the gamma-carboxyglutamic acid (Gla)-domain (des-(1-38) VIIa) resulted in a 10- to 30-fold increase of the Kd for the interaction, as did blocking the Gla-domain by Fab fragments of a specific monoclonal antibody. These results suggest that the VII Gla-domain can participate in protein-protein interaction with the TF molecule per se rather than only in interactions with the charged phospholipid surface. Gla-domain-independent, low affinity binding of VII to TF required micromolar Ca2+, indicating involvement of high affinity calcium ion binding sites suggested to be localized in VII rather than TF. Interference with Gla-domain-dependent interactions with TF did not alter the TF. VIIa dependent cleavage of a small peptidyl substrate, whereas the proteolytic activation of the protein substrate factor X was markedly decreased, suggesting that the VIIa Gla-domain not only participates in the formation of a more stable TF. VIIa complex but contributes to extended substrate recognition. PMID- 1874731 TI - Analysis of the oligomeric state of Band 3, the anion transport protein of the human erythrocyte membrane, by size exclusion high performance liquid chromatography. Oligomeric stability and origin of heterogeneity. AB - The oligomeric state of human Band 3 (Mr = 95,000), the erythrocyte membrane anion exchanger, was examined by size exclusion high performance liquid chromatography in solutions containing the nonionic detergent C12E8 (octaethylene glycol n-dodecyl monoether). Band 3 was heterogeneous with respect to oligomeric composition, the predominant (70%) species being a dimer that bound 0.57 mg of C12E8/mg of protein (Stokes radius = 78 A, s20,w = 6.9 S). Variable amounts of larger oligomers were also present; however, no evidence for equilibration between oligomeric species was observed in detergent solution. Analytical and large zone size exclusion chromatography showed that Band 3 could not be dissociated to monomers, other than by protein denaturation. The membrane domain of Band 3 (Mr = 52,000) was also dimeric, but without evidence for higher oligomeric forms, which implies that the interactions responsible for higher associations involve the cytoplasmic domain. Prelabeling of Band 3 with the anion exchange inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonate had no effect upon the oligomeric state of either intact Band 3 or its 52-kDa membrane domain. Band 3 oligomeric state could be reversibly changed in the membrane by altering the pH of the solution. The fraction of Band 3 not associated with the cytoskeleton was almost entirely dimeric. Band 3 purified from erythrocytes separated by density gradient centrifugation revealed that older red cells contained a larger proportion of higher oligomers than did younger cells. We conclude that Band 3, in the membrane and in C12E8 solution, exists as a mixture of dimers and larger oligomers. The higher oligomers interact with the cytoskeleton, increase in amount with cell age, and are held together by interactions of the cytoplasmic domain. PMID- 1874732 TI - Characterization of an 8-lipoxygenase activity induced by the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate in mouse skin in vivo. AB - An enzymatic activity has been found in cytosolic preparations from mouse epidermis which catalyzes the formation of 8-hydroperoxyeicosatetraenoic acid/8 hydroxyeicosatetraenoic acid (8-HPETE/8-HETE) from arachidonate. In contrast to 12-lipoxygenase this enzyme activity was not detectable in normal (untreated) mouse skin but only after in vivo treatment with the phorbol ester tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate). The induction showed a maximum at 24 h after TPA treatment strictly depended on the age of the mice and the TPA dose and was prevented by cycloheximide. The primary product formed from arachidonic acid was 8-HPETE, and the enzyme seems not to possess a significant peroxidase activity. This result as well as studies with specific inhibitors and its cytosolic localization indicates this enzyme to be a member of the lipoxygenase family. Most of the 8-lipoxygenase activity is located in cells of the suprabasal compartment of the epidermis. In spite of being a cytosolic enzyme 8-lipoxygenase appeared to be lipophilic to some extent and was activated by lecithin. The enzyme did not require calcium ions or ATP and showed a pH optimum at 7.5-8.0. 8 HPETE/8-HETE levels in mouse epidermis in vivo were determined by gas chromatography-mass spectrometry and found to be strongly increased after phorbol ester treatment, in agreement with the induction of 8-lipoxygenase observed. PMID- 1874733 TI - Developmental regulation of proteolytic activities and subunit pattern of 20 S proteasome in chick embryonic muscle. AB - The proteolytic activities of the 20 S proteasome were found to change in their levels during the development of chick embryonic muscle. The peptide-cleaving activities against N-succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin and N benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-beta-naphthylamide gradually decreased with the time of development. On the other hand, the casein-degrading activity in the presence of poly-L-lysine markedly increased from embryonic day 11 and reached a maximal level by day 17. These changes appeared to be tissue-specific because little or no change in any of the proteolytic activities was observed with developing embryonic brain, while dramatic alterations occurred in the extents of the peptide hydrolyses in liver. Furthermore, a number, but not all, of the proteasome subunits in embryonic muscle were changed in their amounts during the development. These results suggest that the alterations in the proteasome activities and subunit pattern are developmentally regulated and may be correlated. PMID- 1874734 TI - The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. AB - Staurosporine is the most potent inhibitor of protein kinase C (PKC) described in the literature with a half-maximal inhibitory concentration (IC50) of 10 nM. Nevertheless, this natural product is poorly selective when assayed against other protein kinases. In order to obtain specific PKC inhibitors, a series of bisindolylmaleimides has been synthesized. Structure-activity relationship studies allowed the determination of the substructure responsible for conferring high potency and lack of selectivity in the staurosporine molecule. Several aminoalkyl bisindolylmaleimides were found to be potent and selective PKC inhibitors (IC50 values from 5 to 70 nM). Among these compounds GF 109203X has been chosen for further studies aiming at the characterization of this chemical family. GF 109203X was a competitive inhibitor with respect to ATP (Ki = 14 +/- 3 NM) and displayed high selectivity for PKC as compared to five different protein kinases. We further determined the potency and specificity of GF 109203X in two cellular models: human platelets and Swiss 3T3 fibroblasts. GF 109203X efficiently prevented PKC-mediated phosphorylations of an Mr = 47,000 protein in platelets and of an Mr = 80,000 protein in Swiss 3T3 cells. In contrast, in the same models, the PKC inhibitor failed to prevent PKC-independent phosphorylations. GF 109203X inhibited collagen- and alpha-thrombin-induced platelet aggregation as well as collagen-triggered ATP secretion. However, ADP dependent reversible aggregation was not modified. In Swiss 3T3 fibroblasts, GF 109203X reversed the inhibition of epidermal growth factor binding induced by phorbol 12,13-dibutyrate and prevented [3H] thymidine incorporation into DNA, only when this was elicited by growth promoting agents which activate PKC. Our results illustrate the potential of GF 109203X as a tool for studying the involvement of PKC in signal transduction pathways. PMID- 1874735 TI - Molecular cloning of a porcine gene syk that encodes a 72-kDa protein-tyrosine kinase showing high susceptibility to proteolysis. AB - By using antibodies raised against a portion of N terminus of 40-kDa kinase (Kobayashi, T., Nakamura, S., Taniguchi, T., and Yamamura, H. (1990) Eur. J. Biochem. 188, 535-540), not only 40-kDa protein but also 72-kDa protein were detected on immunoblot analysis of porcine spleen homogenate. In splenocytes preparation, the antibodies could immunoprecipitate protein-tyrosine kinase activity of the 72-kDa protein but not detect the 40-kDa protein even on immunoblot. After incubation of crude spleen homogenate at 37 degrees C with or without various protease inhibitors, immunoblot analysis revealed proteolytic breakdown of the 72-kDa protein to 40-kDa fragment. Next, using oligonucleotides designed according to partially sequenced information of the 40-kDa kinase as a probe, we have isolated a clone containing entire coding sequence for the 40-kDa kinase from a porcine spleen cDNA library. This clone had a 1884-base-pair-long open reading frame encoding 628-amino-acid polypeptide with a calculated molecular weight of 71,618. The deduced amino acid sequence did not contain a ligand binding or membrane spanning region but did a well-conserved protein tyrosine kinase domain and two src homology region 2 domains. The sequences of these domains showed 30-40% identity to those of other protein-tyrosine kinases, but those of remaining parts were quite unique. From these results, we concluded that the 40-kDa kinase was generated by proteolysis from the 72-kDa holoprotein which was a new member of nonreceptor protein-tyrosine kinase so far reported. We therefore designated this gene as syk after spleen tyrosine kinase. PMID- 1874737 TI - Increased DNA binding and transcriptional activity associated with transcription factor Sp1 in K562 cells transfected with the myeloid-specific c-fes tyrosine kinase gene. AB - Myeloblast cell line K562, when stably transfected with the human genomic c-fes sequence encoding a proto-oncogene tyrosine-protein kinase, acquires the characteristics of more mature granulocytic cells (WS-1 cells) and the ability to undergo differentiation (Yu, G., Smithgall, T. E., and Glazer, R. I. (1989) J. Biol. Chem. 264, 10276-10281). To explore the role of transcription factors in the differentiation process, WS-1 cells were analyzed for the presence of DNA binding proteins capable of interacting with the 5'-long terminal repeat (LTR) region of human immunodeficiency virus (HIV)-1, that contains the binding sequences for transcription factors Sp1 and NFKB. Southwestern blotting and mobility shift assays revealed the presence of Sp1 in K562 and WS-1 cells. The DNA-binding activity of Sp1 was significantly greater in WS-1 cells than in K562 cells, despite the detection by immuno-blotting of equivalent quantities and degrees of heterogeneity of Sp1 in both cell lines. DNA footprinting of the HIV-1 5'-LTR demonstrated that two of the three Sp1-binding sites and both NFKB binding sequences were protected by nuclear extracts from WS-1 cells, while no protection was afforded by nuclear extracts from K562 cells. Analysis of transcription in vitro by primer extension revealed enhanced initiation of transcription from the HIV-1 5'-LTR by nuclear extracts from WS-1 cells, but not from K562 cells. These data indicate that the response evoked by the c-fes tyrosine-protein kinase leads to enhanced DNA binding activity of Sp1 and NFKB, that results in the activation of transcription from the HIV-1 5'-LTR. PMID- 1874736 TI - Activation of the Pseudomonas TOL plasmid upper pathway operon. Identification of binding sites for the positive regulator XylR and for integration host factor protein. AB - Expression of the Pseudomonas putida TOL plasmid upper pathway operon requires a promoter that belongs to the -12/-24 class. Stimulation of transcription from this promoter is positively controlled by the effector-activated XylR protein and requires a form of RNA-polymerase holoenzyme containing the RpoN-encoded sigma factor, sigma 54. XylR-dependent stimulation of transcription from the Pseudomonas TOL upper pathway promoter was examined using deletions, insertions, and in vivo dimethyl sulfate footprinting. Two upstream activator sequences were identified in the -160 (UAS1) and -130 (UAS2) regions. Deletion of these two regions abolished transcription activation, although conservation of the UAS2 element alone allowed limited transcription stimulation. Separation of UAS1 from UAS2 by half a turn or a full turn significantly reduced XylR stimulation of transcription from the upper pathway operon promoter. An inverted repeated ATTTGN2CAAAT (where N is any nucleoside), which most likely represented the XylR recognition sequence, was identified. Binding of XylR was observed in vivo in the absence of effector, but changes in the binding pattern were induced in the presence of m-methylbenzyl alcohol, a XylR effector. In vivo footprinting analysis revealed that changes in the methylation pattern of G and T also occurred in the -50 to -90 region, which is probably occupied by integration host factor (IHF) protein. IHF was required for maximal expression from the TOL upper pathway operon promoter in Escherichia coli. Separation of the IHF site from UAS2 by a full helix turn did not significantly affect stimulation of transcription, which is consistent with this region playing a conformational role, rather than a regulatory one, in promoter function. PMID- 1874738 TI - The chymotrypsin inhibitor carbobenzyloxy-leucine-tyrosine-chloromethylketone interferes with phospholipase D activation induced by formyl-methionyl-leucyl phenylalanine in human neutrophils. AB - The effects of carbobenzyloxy-leucine-tyrosine-chloromethylketone (zLYCK), an inhibitor of chymotrypsin-like proteases, on signal transduction in human neutrophils triggered by the chemoattractant formyl-methionyl-leucyl phenylalanine (fMLP) were investigated. zLYCK (10 microM) inhibited the fMLP induced respiratory burst in neutrophils treated with cytochalasin B. In the presence of zLYCK (10 microM), the activation of phospholipase D in response to fMLP addition was inhibited. zLYCK did not inhibit the binding of [3H] fMLP to its receptor or the enzymic activity of phospholipase D because the response to ionomycin was unaffected. The effect of zLYCK on phospholipase D correlated well with its effects on the accumulation of diglycerides, which was also inhibited in the presence of zLYCK. In electropermeabilized neutrophils, too, zLYCK caused an inhibition of the fMLP-induced respiratory burst and the fMLP-induced activation of phospholipase D. Interestingly, this inhibition could be bypassed by guanosine 5'-O-(thiotriphosphate). We conclude that the inhibition of the respiratory burst in human neutrophils by zLYCK is caused by the selective inhibition of signal transduction leading to activation of phospholipase D and that zLYCK might be a useful probe to study the role of phospholipase D in neutrophil activation. PMID- 1874739 TI - Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data. AB - Data generated in the new National Cancer Institute drug evaluation program, which is based on inhibition of cell growth in 60 human tumor cell lines, were used to compare new compounds with agents of known mechanism of action in terms of their differential cytotoxicity. Two marine natural products, halichondrin B and homohalichondrin B, appeared repeatedly when the data base was probed with known antimitotic agents. We confirmed that both compounds were highly cytotoxic (IC50 values for L1210 murine leukemia cells of 0.3 and 1 nM, respectively), with accumulation of cells arrested in mitosis at toxic concentrations, that both inhibited the polymerization of purified tubulin, and that both inhibited microtubule assembly dependent on microtubule-associated proteins. Limited amounts of homohalichondrin B, the less active agent, were available, so only halichondrin B was studied in detail. Halichondrin B did not interfere with colchicine binding to tubulin, but it was a noncompetitive inhibitor of the binding of vinblastine to tubulin (apparent Ki, 5.0 microM). Halichondrin B was therefore compared with other agents which interfere with the binding of vinca alkaloids to tubulin (vinblastine, maytansine, dolastatin 10, phomopsin A, rhizoxin) in terms of its effects on tubulin polymerization, inhibition of GTP hydrolysis, inhibition of nucleotide exchange, and stabilization of tubulin, as well as the quantitative assessment of its effects on vinca alkaloid binding and inhibition of cell growth. Since halichondrin B was originally isolated from the same organism as the phosphatase inhibitor okadaic acid, and since it is about 50 fold more effective than okadaic acid as an inhibitor of L1210 cell growth, perturbations of cellular microtubules observed following treatment with okadaic acid should be interpreted cautiously. PMID- 1874740 TI - Characterization of regions of fibronectin besides the arginine-glycine-aspartic acid sequence required for adhesive function of the cell-binding domain using site-directed mutagenesis. AB - Previous studies of adhesion mediated by the central cell-binding domain of fibronectin suggest that additional polypeptide information besides the Arg-Gly Asp sequence is required for full activity. We analyzed this putative second, synergistic region of fibronectin more extensively by deletion analysis and oligonucleotide-based site-directed mutagenesis. Resulting mutated fusion proteins expressed using lambda gt11 were assayed for baby hamster kidney fibroblast cell spreading activity. Deletion mutants truncating from the amino terminus showed a decrease of activity in two apparently discrete steps. Complementary studies using a series of overlapped internal deletions designed to retain the repetitive fibronectin structure also indicated that two distinct peptide regions besides the RGD sequence were necessary for full activity. Removal of the carboxyl-terminal region resulted in the greatest loss of activity (greater than or equal to 20- versus 3-5-fold). Very similar results were obtained with HT-1080 cells dependent on the alpha 5 beta 1 integrin receptor for adhesion to fibronectin. An anti-fibronectin monoclonal antibody that inhibits cell adhesion was found to bind to the carboxyl-terminal functional region, and a point mutation caused specific loss of its epitope. These studies reveal unexpected complexity in the organization of these functional regions, which contrasts with adhesion models based only on simple, short peptide recognition sequences. PMID- 1874741 TI - Co- and post-translational processing of the hevein preproprotein of latex of the rubber tree (Hevea brasiliensis) AB - Hevein is a chitin-binding protein of 43 amino acids found in the lutoid body enriched fraction of rubber tree latex. A hevein cDNA clone (HEV1) (Broekaert, W., Lee, H.-i., Kush, A., Nam, C.-H., and Raikhel, N. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 7633-7637) encodes a putative signal sequence of 17 amino acids followed by a polypeptide of 187 amino acids. Interestingly, this polypeptide has two distinct domains: an amino-terminal domain of 43 amino acids, corresponding to mature hevein, and a carboxyl-terminal domain of 144 amino acids. To investigate the mechanisms involved in processing of the protein encoded by HEV1, three domain-specific antisera were raised against fusion proteins harboring the amino-terminal domain (N domain), carboxyl-terminal domain (C domain), and both domains (NC domain). Translocation experiments using an in vitro translation system show that the first 17-amino acid sequence encoded by the cDNA functions as a signal peptide. Immunoblot analysis of proteins extracted from lutoid bodies demonstrates that a 5-kDa protein comigrated with purified mature hevein and cross-reacted with N domain- and NC domain-specific antibodies. A 14-kDa protein was recognized by C domain- and NC domain-specific antibodies. A 20-kDa protein was cross-reactive with all three antibodies. Microsequencing data further suggest that the 5-kDa (amino-terminal domain) and 14-kDa (carboxyl-terminal domain) proteins are post-translational cleavage products of the 20-kDa polypeptide (both domains) which corresponds to the proprotein encoded by HEV1. In addition, it was found that the amino-terminal domain could provide chitin binding properties to a fusion protein bearing it either amino terminally or carboxyl terminally. PMID- 1874742 TI - Arabinogalactan-proteins from the suspension culture medium and plasma membrane of rose cells. AB - Arabinogalactan-proteins (AGPs) that bind to beta-glycosyl Yariv antigens have been purified from the culture medium and plasma membrane of "Paul's Scarlet" rose cells. Starting from culture medium or from plasma membrane vesicles prepared by aqueous two-phase partitioning, the purification procedure involved Yariv antigen-induced precipitation and subsequent chromatographic steps. Two fractions, AGP-(a) and AGP-(b), were obtained from the culture medium, and one AGP fraction was obtained from the plasma membrane. The glycosyl compositions of all three fractions were dominated by arabinosyl and galactosyl residues and included glucuronosyl and other minor residues. Methylation analysis showed that AGP-(a) and AGP-(b) were both highly branched 3,6-galactans with terminal arabinofuranosyl substituents. The amino acid compositions of all three AGPs were high in alanine, hydroxyproline, and serine and/or threonine. The amino-terminal sequence of AGP-(b) contained an alanine-hydroxyproline repeat. While sharing general structural similarity, the AGPs from the plasma membrane and the culture medium were distinguishable by composition and by size and charge, with the plasma membrane AGPs being larger and more negatively charged than the culture medium AGPs. PMID- 1874743 TI - Deficient protein kinase C activity in turnip, a Drosophila learning mutant. AB - The Drosophila mutant turnip was initially isolated based on poor learning performance (Quinn, W.G., Sziber, P.P., and Booker, R. (1979) Nature 277, 212 214). Here we show that turnip is dramatically reduced in protein kinase C (PKC) activity. In addition, turnip flies are deficient in phosphorylation of a 76-kDa head membrane protein (hereafter pp76) which is a major substrate for protein kinase C in homogenates of wild-type flies. Reduced PKC activity, defective pp76 phosphorylation, and most of turnip's learning deficiency co-map genetically to a region on the X-chromosome, 18A5-18D1-2, spanned by the deletion Df(1)JA27. Apparently turnip+ is not a structural gene for PKC because Drosophila PKC genes map elsewhere in the genome. Our results suggest that turnip gene product is required for activation of PKC and that PKC plays a role in associative learning in Drosophila. PMID- 1874744 TI - Sequencing of bovine enamelin ("tuftelin") a novel acidic enamel protein. AB - Enamelins are a major group of 28-70-kDa acidic proteins rich in aspartic acid, glutamic acid, serine, and glycine found in developing and mature extracellular enamel; a unique and highly mineralized ectodermal tissue covering vertebrate teeth. They have been associated with the mineralization and structural organization of this tissue. In an attempt to elucidate the primary structure of enamelin, a 2674-base pair cDNA isolated from a bovine ameloblast-enriched, lambda Zap 2 expression library, was sequenced. The identity and localization of the deduced protein was confirmed by amino acid composition, enzyme-linked immunosorbent assay, Western blotting, indirect immunohistochemistry, and high resolution protein-A gold immunocytochemistry. The immunological techniques were employed using antibodies directed against synthetic peptides corresponding to the protein sequence deduced from the cloned cDNA sequence. The results reveal the deduced protein to be a novel acidic enamel protein. It contains 389 amino acids and has a calculated molecular weight of 43,814. Its amino acid composition is similar to that of "tuft" proteins (enamel matrix protein fragments remaining in the mature tissue). It contains one potential N-glycosylation site and 5 cysteine residues. Southern hybridization of the cloned cDNA with genomic bovine DNA indicated the existence of a single gene with one or more introns. PMID- 1874745 TI - Molecular cloning and analysis of the rat kallikrein-binding protein gene. AB - The gene encoding rat kallikrein-binding protein (RKBP), a serine protease inhibitor, has been isolated and analyzed with the aid of the polymerase chain reaction. The gene is approximately 10 kilobases in length with four introns of approximately 2.2, 1.8, 0.9, and 0.84 kilobases. This gene is composed of five exons and encodes a polypeptide of 416 amino acid residues. The reactive center region of RKBP is encoded by the fifth exon with the putative P1-P1' residues being Lys-Ser. The organization of the RKBP gene is homologous to those of human alpha 1-antitrypsin and alpha 1-antichymotrypsin in size and arrangement of exons and introns, suggesting that they belong to the same subgroup of serpins. In the 5'-flanking region of the RKBP gene, a variant TATA box sequence, ATAAATA, is found 20 base pairs upstream from the transcription initiation site. The 5' flanking region of the RKBP gene was able to direct transcription of the reporter gene chloramphenicol acetyltransferase when transfected into a rat hepatoma cell line. An internal promoter-like region was found in the first intron of the RKBP gene, downstream from the transcription initiation site and upstream from the translation initiation codon, however, it was unable to direct expression of the chloramphenicol acetyltransferase reporter gene in our experiments. The expression of RKBP in rat liver was induced by sex hormone treatment as indicated by dot-blot analysis. A genomic Southern blot using an RKBP cDNA probe revealed multiple bands suggesting that the RKBP gene belongs to a family of highly conserved genes. PMID- 1874746 TI - Analysis of the molecular mechanisms for the species-specific transcription of Drosophila and human tRNA gene transcription components. AB - The transcription of eucaryotic tRNA genes requires two factors IIIB and IIIC, in addition to RNA polymerase III, to reconstitute this process in vitro. We have examined the functional exchangeability of these components from Drosophila and human systems. The reconstitution of heterologous IIIB and IIIC components demonstrated that neither factor will functionally substitute for the homologous components to activate tRNA gene transcription. The addition of the heterologous Drosophila factors to HeLa transcription assays causes an inhibition of RNA synthesis that is dependent upon the order of addition of these proteins to the DNA template. Thus, it appears that tRNA gene transcription in these systems is species-specific. We have further analyzed the reason for the apparent incompatibilities of these components by the use of stable complex formation assays. We find that human HeLa IIIB and Drosophila IIIC are unable to form stably associated complexes with a tRNA gene template, whereas the Drosophila IIIB and HeLa IIIC do form stable but nonproductive complexes. These results demonstrate that specific IIIC-IIIB interactions are critical in the formation of productive transcription complexes and are responsible for the observed species specificity of Drosophila and human tRNA gene transcription. PMID- 1874747 TI - Ceramide stimulates epidermal growth factor receptor phosphorylation in A431 human epidermoid carcinoma cells. Evidence that ceramide may mediate sphingosine action. AB - Recent studies suggest the existence of a signal transduction pathway involving sphingomyelin and derivatives (Kolesnick, R. N. (1989) J. Biol. Chem. 264, 7617 7623). The present studies compare effects of ceramide, sphingosine, and N,N dimethylsphingosine on epidermal growth factor (EGF) receptor phosphorylation in A431 human epidermoid carcinoma cells. To increase ceramide solubility, a ceramide containing octanoic acid at the second position (C8-cer) was synthesized. C8-cer induced time- and concentration-dependent EGF receptor phosphorylation. This event was detectable by 2 min and maximal by 10 min. As little as 0.1 microM C8-cer was effective, and 3 microM C8-cer induced maximal phosphorylation to 1.9-fold of control. EGF (20 nM) increased phosphorylation to 2.1-fold of control. Sphingosine stimulated receptor phosphorylation over the same concentration range (0.03-3 microM) and to the same extent (1.8-fold of control) as ceramide. The effects of C8-cer and sphingosine were similar by three separate criteria, phosphoamino acid analysis, anti-phosphotyrosine antibody immunoblotting, and phosphopeptide mapping by high performance liquid chromatography. Phosphorylation occurred specifically on threonine residues. N,N Dimethylsphingosine, a potential derivative of sphingosine, was less effective. Since sphingosine and ceramide are interconvertible, the level of each compound was measured under conditions sufficient for EGF receptor phosphorylation. C8-cer (0.1-1 microM) induced dose-responsive elevation of cellular ceramide from 132 to 232 pmol.10(6) cells-1. In contrast, cellular sphingosine levels did not rise. This suggests that C8-cer acts without conversion to sphingosine. Exogenous sphingosine (0.1-1 microM) also increased cellular ceramide levels to 227 pmol.10(6) cells-1, but did not increase its own cellular level of 12 pmol.10(6) cells-1. Higher sphingosine concentrations that induced no further increase in EGF receptor phosphorylation produced very large elevations in cellular sphingosine. Hence, at effective concentrations, both compounds elevated cellular ceramide but not sphingosine levels. Additional studies performed with [3H]sphingosine demonstrated that cells contain substantially less N,N dimethylsphingosine than free sphingosine and, during short term incubation, convert less than 5% of added sphingosine to N,N-dimethylsphingosine. These studies provide evidence that ceramide may have bioeffector properties and suggest sphingosine may act in part by conversion to ceramide. PMID- 1874748 TI - A putative glutathione-binding site in T4 glutaredoxin investigated by site directed mutagenesis. AB - A glutathione monomer has been docked into the active site cleft of T4 glutaredoxin (previously called T4 thioredoxin) using molecular graphics. The central part of the cleft is formed by the side chain of Tyr-16 on one side and the residues Thr-64, Met-65, and Pro-66 on the other. The entire glutathione molecule fits well into the cleft. A cis-peptide bond between the residues Met-65 and Pro-66 allows glutathione to bind in an anti-parallel fashion to residues 64 66. Hydrogen bonds can be formed between Met-65 and the glutathione cysteine. This binding positions the glutathione sulfur atom ideally for reaction with the glutaredoxin disulfide. In the model, glutathione can form a hydrogen bond to the hydroxyl group of Tyr-16. Charged interactions at opposite ends of the binding cleft are provided by His-12 and Asp-80. The negatively charged alpha-carboxyl group of glutathione may interact with a positive helix dipole of the protein. Fifteen mutant T4 glutaredoxins have been produced and assayed for glutathione binding by determining thioltransferase activity. Mutant proteins with substitutions in the sides of the cleft (Tyr-16, Pro-66) exhibited the most marked decreases in thioltransferase activity. Mutation of His-12 to a serine decreases the catalytic efficiency whereas substitution of Asp-80 by serine increases the catalytic efficiency. A double mutant, D80S;H12S, has much less affinity for glutathione than either single mutant. Substitution of Cys-14 produces an inactive protein, whereas C17S retains some thioltransferase activity. PMID- 1874749 TI - An engineered liver glycogen phosphorylase with AMP allosteric activation. AB - Liver and muscle glycogen phosphorylases, which are products of distinct genes, are both activated by covalent phosphorylation, but in the unphosphorylated (b) state, only the muscle isozyme is efficiently activated by the allosteric activator AMP. The different responsiveness of the phosphorylase isozymes to allosteric ligands is important for the maintenance of tissue and whole body glucose homeostasis. In an attempt to understand the structural determinants of differential sensitivity of the muscle and liver isozymes to AMP, we have developed a bacterial expression system for the liver enzyme, allowing native and engineered proteins to be expressed and characterized. Engineering of the single amino acid substitutions Thr48Pro, Met197Thr and the double mutant Thr48Pro, Met197Thr in liver phosphorylase, and Pro48Thr in muscle phosphorylase, did not qualitatively change the response of the two isozymes to AMP. These sites had previously been implicated in the configuration of the AMP binding site. However, when nine amino acids among the first 48 in liver phosphorylase were replaced with the corresponding muscle phosphorylase residues (L1M2-48L49-846), the engineered liver enzyme was activated by AMP to a higher maximal activity than native liver phosphorylase. Interestingly, the homotropic cooperativity of AMP binding was unchanged in the engineered phosphorylase b protein, and heterotropic cooperativity between the glucose-1-phosphate and AMP sites was only slightly enhanced. The native liver, native muscle and L1M2-48L49-846 phosphorylases were converted to the a form by treatment with purified phosphorylase kinase; the maximal activity of the chimeric a enzyme was greater than the native liver a enzyme and approached that of muscle phosphorylase a. From these results we suggest that tissue-specific phosphorylase isozymes have evolved a complex mechanism in which the N-terminal 48 amino acids modulate intrinsic activity (Vmax), probably by affecting subunit interactions, and other, as yet undefined regions specify the allosteric interactions with ligands and substrates. PMID- 1874750 TI - Cleavage of vasoactive intestinal peptide at multiple sites by autoantibodies. AB - Vasoactive intestinal peptide (VIP) fragments generated by autoantibodies purified from the blood of two human beings were separated and sequenced. Based on the identity of these fragments, seven peptide bonds cleaved by the antibodies were identified. Six of the seven scissile bonds are clustered in the region of VIP spanning residues 14-22 and were cleaved by antibodies from both human subjects. The seventh scissile bond is located at residues 7-8 and was cleaved by antibodies from one of the subjects. The scissile bonds link amino acid residues with different size, charge, and hydrophobicity. The hydrolytic activity of the antibodies was selective in that they failed to hydrolyze polypeptides unrelated in sequence to VIP (insulin and atrial natriuretic peptide). These observations demonstrate substrate specific hydrolysis by naturally occurring antibodies and expand the range of peptide bonds hydrolyzed by these antibodies. PMID- 1874751 TI - Role of the NADP/thioredoxin system in the reduction of alpha-amylase and trypsin inhibitor proteins. AB - Thioredoxin, reduced either enzymatically with NADPH and NADP-thioredoxin reductase or chemically with dithiothreitol, reduced alpha-amylase and trypsin inhibitor proteins from several sources. Included were cystine-rich seed representatives from wheat (alpha-amylase inhibitors), soybean (Bowman-Birk trypsin inhibitor), and corn (kernel trypsin inhibitor). This system also reduced other trypsin inhibitors: the soybean Kunitz inhibitor, bovine lung aprotinin, and egg white ovoinhibitor and ovomucoid proteins. The ability of these proteins to undergo reduction by thioredoxin was determined by 1) a coupled enzyme activation assay with chloroplast NADP-malate dehydrogenase or fructose-1,6 bisphosphatase, 2) a dye reduction assay with 5',5'-dithiobis(2-nitrobenzoic acid), and 3) a direct reduction method based on the fluorescent probe, monobromobimane, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Reduction experiments with the seed proteins were carried out with thioredoxin from wheat germ (h-type) or Escherichia coli; the corresponding experiments with the animal trypsin inhibitors were carried out with thioredoxin from calf thymus or E. coli. In all cases, thioredoxin appeared to act catalytically; the reduced form of glutathione was without effect. When considered in conjunction with earlier results on purothionin (confirmed and extended in the current study), the new findings suggest that the NADP/thioredoxin system functions in the reduction of protein inhibitors of seeds and animal tissues. These results also raise the question of the occurrence of glutaredoxin in plants, as E. coli glutaredoxin was found to promote the reduction of some but not all of the proteins tested. PMID- 1874752 TI - Phosphorylation of numatrin and other nuclear proteins by cdc2 containing CTD kinase cdc2/p58. AB - Numatrin is a nuclear matrix phosphoprotein whose synthesis and abundance were shown to be regulated during the cell cycle in mitogen-stimulated lymphocytes (Feuerstein, N., and Mond, J. (1987) J. Biol. Chem. 262, 11389-11397). We examined the effect of (a) CTD-kinase, which contains the cdc2 catalytic component (p34) in a complex with a p58 subunit (cdc2/p58) and (b) the M phase specific histone H1 kinase, which contains the cdc2 kinase in association with a p62 subunit (cdc2/p62), on phosphorylation of numatrin. We show that both cdc2 kinase complexes can phosphorylate numatrin. However, cdc2/p58 at conditions that caused a similar effect to cdc2/p62 on phosphorylation of histone H1 (dpm/micrograms of substrate/micrograms of enzyme) was found to have a 5-25-fold higher catalytic activity in the phosphorylation of numatrin. Analysis of the tryptic phosphopeptide map of numatrin phosphorylated by these cdc2 kinase complexes showed that both kinase complexes phosphorylated two major identical peptides, but minor additional peptides were differentially phosphorylated by each of these kinases. This indicates that under certain experimental conditions cdc2/p58 and cdc2/p62 may express some differences in their catalytic activity. In vitro phosphorylation by CTD kinase of a whole nuclear protein extract from murine fibroblasts showed that numatrin is the most prominent substrate for CTD kinase in this nuclear extract. CTD kinase cdc2/p58 was found to induce significantly the phosphorylation of five other discrete nuclear substrates. Particularly, two nuclear proteins at 75 kDa/pI approximately 6.5 and 85 kDa/pI approximately 5.3, which were not Coomassie Blue stainable, were found to be markedly phosphorylated by CTD kinase. The results of this study call for further study of the role of CTD kinase cdc2/p58 in the phosphorylation of numatrin under physiological conditions and to further characterization of the other nuclear substrates for CTD kinase. PMID- 1874753 TI - Membrane-microfilament interactions in ascites tumor cell microvilli. Identification and isolation of a large microfilament-associated membrane glycoprotein complex. AB - [14C]Glucosamine metabolic labeling and concanavalin A blots were used to identify four major glycoprotein species associated with ascites tumor cell microvillar microfilament cores and with a transmembrane complex containing actin. Phalloidin shift analysis of glucosamine-labeled microvilli showed that glycoproteins of 110-120, 80, 65, and 55 kDa are stably associated with the microfilament cores. Analysis of large (greater than 10(6) kDa) transmembrane complexes from microvillar membranes made under microfilament-depolymerizing conditions (Carraway, C. A. C., Jung, G., and Carraway, K. L. (1983) Proc. Natl. Acad. Sci. U. S. A. 80, 430-434) revealed glycoproteins of the same Mr values, showing the same relative staining or labeling patterns as those observed with the microfilament cores. Gel filtration of high salt, high pH extracts of intact microvilli, microfilament cores, or transmembrane complexes showed that in all of these fractions the glycoproteins are associated in a very large, stable complex. The glycoprotein multimer was isolated essentially free of actin and other components by Sephacryl S-1000 chromatography of microvilli, microvillar membranes prepared at pH 11, microfilament cores, or transmembrane complex fractions in Triton X-100, 1 M KCl, glycine, pH 9.5. Purified glycoprotein complex bound actin when incubated under polymerizing conditions. The presence of the glycoprotein heteromultimer in both microfilament cores and transmembrane complex from isolated membranes and the association of the purified glycoprotein complex with actin are consistent with our hypothesis that the glycoprotein containing transmembrane complex is an association site for microfilaments at the plasma membrane. PMID- 1874754 TI - Phospholipid-independent and -dependent interactions required for tissue factor receptor and cofactor function. PMID- 1874755 TI - Hylan gel composition for percutaneous embolization. AB - Viscoelastic, pseudoplastic, radiopaque injectable hylan gel for percutaneous embolization was developed and evaluated by in vitro and in vivo tests. The embolization gel is composed of cross-linked hylan (hyaluronan, hyaluronate), tantalum, microcrystalline cellulose, hexamethonium chloride, and thrombin. Upon delivery through small-lumen catheters to the appropriate vascular site, the gel induces formation of a solid blood/gel coagulum. Results from animal studies (rat aorta, rabbit auricular artery) demonstrate that formation of complete and long lasting arterial blockage is readily achievable without complications due to blood flow, partial vessel obstruction, uncontrolled polymerization, or movement of the gel or its components (specifically thrombin and hexamethonium chloride) into the circulation. Microscopic evaluation indicates that arterial occlusion initially occurs as a result of the injected gel and formed fibrin; at 7 weeks and beyond, arteries are occluded by injected gel, inflammatory cells and fibrosis (scar tissue). PMID- 1874756 TI - Osteoblast responses to orthopedic implant materials in vitro. AB - Responses of neonatal rat calvarial osteoblasts to a variety of orthopedic implant materials were examined in vitro. Attachment, proliferation, and collagen synthesis of a well-characterized line of osteoblasts with 316L stainless steel, Ti-6Al-4V, Co-Cr-Mo, PMMA, hydroxyapatite, borosilicate glass, and tissue culture polystyrene were studied. Cell adhesion and growth were similar on nonapatitic materials. In contrast, attachment and growth of osteoblasts were significantly lower and slower, respectively, on hydroxyapatite. Collagen synthesis per cell and relative collagen synthesis, however, were comparable on all the materials tested. PMID- 1874757 TI - Effect of some additives on the biostability of a poly(etherurethane) elastomer. AB - Four materials based on a single poly-(etherurethane) (PEU) prepared from MDI and PTMEG but differing in additives were studied in the cage implant system. The two additives studied were Santowhite powder at the 1% level and Methacrol 2138F 5%. Methacrol 2138F appeared to be immiscible with the base PEU and was dispersed in discrete domains about 0.5-micron in size. The retrieved PEU specimens were also cleaned and examined in the optical and scanning electron microscopes, and the size and density of adherent foreign body giant cells (FBGCs) were measured at implantation times up to 10 weeks. Methacrol 2138F had no effect on the density, coverage or size distribution of adherent FBGCs, but leaching of Methacrol 2138F was considered to be responsible for extensive pitting of the PEU surface. On the other hand, Santowhite powder appeared to inhibit formation of FBGCs, and while surface cracking and flaking were observed as early as 3 weeks postimplantation on some PEUs, the Santowhite powder effectively inhibited surface cracking and flaking up to the longest implantation time studied. PMID- 1874758 TI - Fibroblast and hepatocyte behavior on synthetic polymer surfaces. AB - Biodegradable poly(phosphoesters) with varying side group chemistry and copolymers of styrene and methyl vinyl ketone (MVK) with varying degrees of hydrophobicity were used to study the growth and behavior of surface-attached fibroblasts and hepatocytes. Mouse 3T3 fibroblasts and chicken embryo fibroblasts attached and proliferated on all of the polymers tested. Fewer cells attached to copolymers of styrene and MVK than to glass or tissue culture polystyrene controls; cell attachment to several poly(phosphoester) surfaces was indistinguishable from controls. The mean speed of fibroblast migration was faster on surfaces where fewer cells attached (59 to 84 microns/h on low attachment surfaces compared with 40 to 46 microns/h on high attachment surfaces). When surface-attached cells were stained with fluorescently labeled phalloidin, only a fraction of the cells on low attachment surfaces were shown to have prominent arrays of actin filament bundles. Chicken hepatocytes also attached to the polymer surfaces. When a suspension containing a large number of cells was placed over the polymer surfaces, approximately 50% of the hepatocytes attached during the first 9 h. Surprisingly, hepatocyte attachment and viability in culture were relatively insensitive to the chemistry of the synthetic polymer substrates. Cell number increased by about a factor of 2 over the first 48 h of culture, then decreased back to approximately 50% of initial cell number over the next several days. Cell morphology did depend on the chemical structure of the substrates. PMID- 1874759 TI - Polymorphonuclear leukocyte degranulation with exposure to polymethylmethacrylate nanoparticles. AB - Polymethylmethacrylate (PMMA) is clinically employed in a wide range of orthopaedic procedures. The etiology of the inflammatory reaction of recipient tissues to PMMA remains unresolved. Classically, polymorphonuclear leukocytes (PMNs) release cytoplasmic lysosomal granules when exposed to a variety of proinflammatory stimuli. Such degranulation contributes, and partially defines, the local tissue reaction to this foreign material. In the present investigation, PMMA particles (50-60 nm) were mixed with human PMNs, and the amount of lactate dehydrogenase, lysozyme, and beta-glucuronidase released from the cells was quantitated. In all cases, a dose-dependent increase in degranulation followed the addition of increasing amounts of PMMA to the PMNs. In addition, the migration of PMNs was diminished in a dose-dependent manner with exposure to increasing amounts of the cement. These results suggested that PMMA stimulates the release of leukocyte lysosomal contents and alters the migration characteristics of these cells in a manner that is consistent with the local inflammatory reaction to this cement. PMID- 1874760 TI - In vitro degradation of a poly(ether urethane) by trypsin. AB - In vitro enzymatic degradation of non-porous films of segmented poly(ether urethane) (Pellethane 2363-80AE) was investigated by incubating the biomaterial in concentrated trypsin solutions for 5 months at room temperature. Chemical degradation of films was monitored by surface analysis techniques such as Fourier transform infrared spectroscopy-attenuated total reflectance and electron spectroscopy for chemical analysis. This latter technique proved to be much superior in detecting chemical changes. Extraction of films with methanol and characterization of the extracts by gel permeation chromatography revealed the presence of low-molecular-weight polymers. Results have shown that trypsin has the ability to induce degradation in PEU, the soft segment being most affected, particularly the CH2-O bond of the ether linkages. PMID- 1874761 TI - Heparin immobilization increased through chemical amplification. PMID- 1874762 TI - Radiographic detection of metal-induced synovitis as a complication of arthroplasty of the knee. AB - Radiographs of eighteen patients who had had a diagnosis of metal-induced synovitis subsequent to a knee-replacement arthroplasty were retrospectively reviewed. The presence of a dense line outlining a portion of the capsule or articular surface of the knee joint (the so-called metal-line sign) was noted in association with wear in eleven patients. In the nine patients who had a positive sign and also had specimens available for histological examination, there was dense deposition of metal particles, whereas in the six patients who did not have a metal-line sign and had specimens available for histological examination, five had only a slight amount of metal in the synovial tissue and one, a moderate amount. The presence of the metal-line sign was associated with metal-induced synovitis in eleven of the eighteen patients. The sign should be useful in helping to make this diagnosis preoperatively in many patients. PMID- 1874763 TI - Arthrodesis with dual plates after failed total knee arthroplasty. AB - Eleven patients were treated by arthrodesis with dual compression plates after failed total knee arthroplasty. All patients had a solid fusion, at an average of 5.6 months after the operation. The complications included one femoral stress fracture and one persistent infection, both of which were treated successfully. Fixation with dual compression plates is a useful technique for the salvage of a failed total knee arthroplasty, even when the patient has an infection. Staggering of the plates may help to prevent late stress fractures. PMID- 1874764 TI - Electrical stimulation of the thigh muscles after reconstruction of the anterior cruciate ligament. Effects of electrically elicited contraction of the quadriceps femoris and hamstring muscles on gait and on strength of the thigh muscles. AB - The effects of neuromuscular electrical stimulation on the strength of the thigh muscles and on gait were examined in ten patients after reconstruction of the anterior cruciate ligament. The patients were randomly assigned to one of two treatment groups: neuromuscular electrical stimulation and volitional exercise, or volitional exercise alone. A four-week course of electrically elicited co contraction of the thigh muscles resulted in significant attenuation of the characteristic loss of strength of the quadriceps as compared with volitional exercise. There was no significant difference between groups in any measure of performance of the hamstring muscles. In the group that received neuromuscular electrical stimulation, the values for cadence, walking velocity, stance time of the involved limb, and flexion-excursion of the knee during stance were significantly different from those of the volitional exercise group. Flexion excursion of the knee during stance was directly and significantly correlated with strength of the quadriceps femoris muscle. Flexion of the knee during stance was qualitatively different in the involved extremity as compared with the uninvolved extremity in all patients. There is a rapid flexion of the knee at weight acceptance that is maintained throughout stance and probably reflects stabilization of the joint by muscular coactivation to compensate for weakness of the quadriceps. The patients who received neuromuscular electrical stimulation had stronger quadriceps muscles and more normal gait patterns than those in the volitional exercise group. PMID- 1874765 TI - Blood loss after total knee replacement. Effects of tourniquet release and continuous passive motion. AB - We prospectively studied the cases of 121 patients who were being operated on for insertion of a unilateral total knee prosthesis with cement, and we placed them randomly in four groups. In Group I, the tourniquet was inflated throughout the operative procedure, and we released it postoperatively after a compressive dressing had been applied; a splint was used postoperatively for three days. In Group II, the tourniquet remained inflated throughout the operation, but no splint was applied postoperatively, and continuous passive motion was started immediately in the recovery room. In Group III, the tourniquet was released intraoperatively, and hemostasis was achieved by cauterization; postoperatively, a compressive dressing was applied, and a splint was used for three days. In Group IV, the tourniquet was released intraoperatively, hemostasis was established, and then the tourniquet was reinflated; a compressive dressing was applied, and continuous passive motion was started immediately in the recovery room. Hemoglobin and hematocrit values were monitored in all patients. Blood loss in suction drainage was recorded, and the total blood loss was calculated. The results show that total knee arthroplasty is associated with major loss of blood (mean, 1518 milliliters). The calculated blood loss for Groups I, II, and III averaged 1443 milliliters, while that for Group IV averaged 1793 milliliters. Loss in suction drainage correlated with total estimated blood loss and averaged 511 milliliters. The magnitude of blood loss after total knee arthroplasty should be appreciated, and special attention should be paid to the availability of adequate fluid and blood products, preferably blood donated by the patient preoperatively. PMID- 1874766 TI - Patellofemoral pain caused by overactivity. A prospective study of risk factors in infantry recruits. AB - A prospective study of 390 infantry recruits revealed that the medial tibial intercondylar distance and that the isometric strength of the quadriceps, tested at 85 degrees of flexion of the knee, had a statistically significant correlation with the incidence of patellofemoral pain caused by overactivity. Increased medial tibial intercondylar distance and increased strength of the quadriceps were therefore deemed to be risk factors for this syndrome. PMID- 1874767 TI - Prophylaxis against infection. Single-dose cefonicid compared with multiple-dose cefamandole. AB - A total of 1489 patients were included in a prospective, randomized study that compared the efficacy of a single dose of cefonicid in 474 patients (Group I) with that of three doses of cefamandole in 510 patients (Group II) and five doses of cefamandole in 505 patients (Group III), for prophylaxis against infection after an operation on bone. The operations involved the insertion of a Moore prosthesis, an Ender and Kuntscher nail, a bone-plate, or another device for internal fixation. Patients who had an open fracture or a total joint replacement were not included in the study. The three groups were similar with regard to mean age, sex ratio, duration of preoperative hospitalization, underlying risk factors, and type of operation. The rates of wound infection were not significantly different in the three groups (p = 0.8) or when the rates were stratified according to the type of operation (p greater than 0.3). Staphylococcus aureus and gram-negative bacilli were the most common infecting microorganisms. The rate of mortality related to infection was similar in all three groups (p = 0.2). No adverse side-effects of drugs were encountered. A single preoperative dose of cefonicid, three doses of cefamandole, and five doses of cefamandole were equally effective prophylaxis against infection of the wound in these patients. PMID- 1874768 TI - Lateral distraction injuries to the thoracic and lumbar spine. A report of three cases. AB - Three patients sustained a lateral distraction injury to the thoracic or lumbar spine. These injuries were associated with multiple fractures of the ribs and extremities as well as with thoracic and abdominal visceral injuries. No patient had an injury to the spinal cord or cauda equina. The injuries to the spine were successfully treated with open reduction of the unilateral subluxation of the facet joint and with internal fixation with Harrington instrumentation. Fusion was achieved with the spine in anatomical alignment, without any complications, in all three patients. PMID- 1874769 TI - Transient penetration of the hip joint during in situ cannulated-screw fixation of slipped capital femoral epiphysis. AB - Before the routine intraoperative use of fluoroscopy at our institution during procedures to stabilize a slipped capital femoral epiphysis, twenty-five patients (thirty hips) had in situ cannulated-screw stabilization of a slipped capital femoral epiphysis with use of biplane radiography. Thus, a permanent record of the procedure was available for review. Fourteen hips in fourteen patients had an intraoperative episode during which the joint was penetrated by the guide-pin assembly or cannulated screw, or both. This penetration was corrected at the time of the operation. Eleven patients were followed for a minimum of two years (mean, thirty-nine months; range, twenty-four to sixty-three months). All physes went on to closure. None of the patients had clinical or radiographic evidence of chondrolysis. Transient penetration of the hip joint did not lead to chondrolysis in this series. This suggests that a single episode of penetration by a pin or screw, with immediate removal from the joint, is not associated with the development of chondrolysis. PMID- 1874770 TI - The inferior transverse scapular ligament as a possible cause of entrapment neuropathy of the nerve to the infraspinatus. A brief note. PMID- 1874771 TI - Nerve palsy associated with total hip replacement. Risk factors and prognosis. AB - We reviewed the results of 3126 consecutive total hip replacements and identified postoperative neuropathy in the ipsilateral lower extremity after fifty-three (1.7 per cent) over-all and after 1.3 per cent of the primary arthroplasties. The prevalence was 5.2 per cent after the primary arthroplasties that had been done for congenital dislocation or dysplasia of the hip and 3.2 per cent after the revisions (all diagnoses). Thus, these two types of operations were risk factors (p less than 0.01). Limb-lengthening only partially accounted for the increased prevalence of neuropathy after these procedures. The sciatic nerve was involved in all but five extremities. The cause of the palsy was unclear or unknown in thirty (57 per cent) of the extremities. When the patients were last seen, at a minimum of one year and a maximum of sixteen and one-half years after the operation, seven extremities were normal neurologically, thirty-three had a mild neurological deficit, and thirteen had a major deficit. All patients who had complete recovery of neurological function had it by twenty-one months. Of thirty six extremities that were evaluated at a minimum of twenty-four months after the operation, seven were neurologically normal, twenty-three had a mild persistent deficit, and six had a major persistent deficit. The ability to walk decreased for all patients who had a nerve palsy. The greatest disability was in the patients who had been forty-eight years old or less and had had a primary total hip replacement (p = 0.037). The prognosis for neurological recovery was related to the degree to which the nerve was damaged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874772 TI - Recurrent Legg-Calve-Perthes disease. Case report and review of the literature. PMID- 1874773 TI - Familial congenital unilateral anterior dislocation of the radial head: differentiation from traumatic dislocation by means of arthrography. A case report. PMID- 1874774 TI - Simple bone cysts of the pelvis in adolescents. A report of four cases. PMID- 1874775 TI - The piriformis syndrome. A case report. PMID- 1874776 TI - Flexion-distraction fracture of the cervical spine. A case report. PMID- 1874777 TI - Epidural lipoma causing a myelographic block in a patient who had sciatica and lumbosacral spondylolisthesis. A case report. PMID- 1874778 TI - Methods to reduce intraoperative transmission of blood-borne disease. PMID- 1874779 TI - Unsatisfactory results with a ceramic total hip prosthesis. PMID- 1874780 TI - Abnormal magnetic-resonance scans of the cervical spine in asymptomatic subjects. PMID- 1874781 TI - Data versus meaningless facts. PMID- 1874782 TI - Total acromionectomy. A twenty-year review. AB - Thirty-five patients (thirty-eight shoulders) were treated consecutively with a total acromionectomy between 1969 and 1989. At a minimum of two years (average, five years and eight months) after the operation, thirty-one patients (thirty four shoulders) were available for review. The results, which were rated on the basis of pain, function, range of motion, strength, and the satisfaction of the patient, were excellent for twenty-five shoulders, good for four, fair for three, and poor for one. Four of the five least satisfactory results were in patients who had had a long-standing massive tear of the rotator cuff. This study was done to separate the criticism of the operative procedure of total acromionectomy from an avoidable complication of that procedure, retraction of the deltoid, and to describe the specific advantages and satisfactory results that occur when that complication is avoided. It is my opinion that failure to repair the deltoid adequately results in retraction of that muscle, and that this avoidable complication is responsible for the unfavorable reputation of total acromionectomy. PMID- 1874783 TI - Complications of a failed Bristow procedure and their management. AB - The management of patients who have a failed Bristow reconstruction of the shoulder is very complex. In order to determine the complications that occur when a Bristow procedure fails, and how they should be managed, we retrospectively evaluated forty shoulders in thirty-nine patients who had been treated by the senior one of us for a failed Bristow procedure from 1977 to 1987. The complications of the index Bristow procedures included recurrent painful anterior instability, injury to the articular cartilage, failure of the coracoid bone block to unite with the glenoid, loosening of the screw, neurovascular injury, and posterior instability. The primary etiology of failure of the index Bristow procedure was excessive laxity of the capsule in thirty-two shoulders (80 per cent) that were affected by chronic, painful anterior or posterior instability. An untreated Perthes-Bankart lesion was present in the remaining eight shoulders (20 per cent). The use of anterior reconstruction for the revision of a failed Bristow procedure is a difficult operation that necessitates meticulous technique. As our over-all plan of treatment resulted in a good or excellent outcome in only 50 per cent of the patients, we do not recommend the Bristow procedure for primary treatment of symptomatic anterior instability of the shoulder. PMID- 1874784 TI - Repairs of the rotator cuff. Correlation of functional results with integrity of the cuff. AB - We evaluated the results of 105 operative repairs of tears of the rotator cuff of the shoulder in eighty-nine patients at an average of five years postoperatively. We correlated the functional result with the integrity of the cuff, as determined by ultrasonography. Eighty per cent of the repairs of a tear involving only the supraspinatus tendon were intact at the time of the most recent follow-up, while more than 50 per cent of the repairs of a tear involving more than the supraspinatus tendon had a recurrent defect. Older patients and patients in whom a larger tear had been repaired had a greater prevalence of recurrent defects. At the time of the most recent follow-up, most of the patients were more comfortable and were satisfied with the result of the repair, even when they had sonographic evidence of a recurrent defect. The shoulders in which the repaired cuff was intact at the time of follow-up had better function during activities of daily living and a better range of active flexion (129 +/- 20 degrees compared with 71 +/- 41 degrees) compared with the shoulders that had a large recurrent defect. Similar correlations were noted for the range of active external and internal rotation and for strength of flexion, abduction, and internal rotation. In the shoulders in which the cuff was not intact, the degree of functional loss was related to the size of the recurrent defect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874785 TI - Preferential attachment of membrane glycoproteins to the cytoskeleton at the leading edge of lamella. AB - The active forward movement of cells is often associated with the rearward transport of particles over the surfaces of their lamellae. Unlike the rest of the lamella, we found that the leading edge (within 0.5 microns of the cell boundary) is specialized for rearward transport of membrane-bound particles, such as Con A-coated latex microspheres. Using a single-beam optical gradient trap (optical tweezers) to apply restraining forces to particles, we can capture, move and release particles at will. When first bound on the central lamellar surface, Con A-coated particles would diffuse randomly; when such bound particles were brought to the leading edge of the lamella with the optical tweezers, they were often transported rearward. As in our previous studies, particle transport occurred with a concurrent decrease in apparent diffusion coefficient, consistent with attachment to the cytoskeleton. For particles at the leading edge of the lamella, weak attachment to the cytoskeleton and transport occurred with a half time of 3 s; equivalent particles elsewhere on the lamella showed no detectable attachment when monitored for several minutes. Particles held on the cell surface by the laser trap attached more strongly to the cytoskeleton with time. These particles could escape a trapping force of 0.7 X 10(-6) dyne after 18 +/- 14 (sd) s at the leading edge, and after 64 +/- 34 (SD) s elsewhere on the lamella. Fluorescent succinylated Con A staining showed no corresponding concentration of general glycoproteins at the leading edge, but cytochalasin D-resistant filamentous actin was found at the leading edge. Our results have implications for cell motility: if the forces used for rearward particle transport were applied to a rigid substratum, cells would move forward. Such a mechanism would be most efficient if the leading edge of the cell contained preferential sites for attachment and transport. PMID- 1874786 TI - Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell-cell adhesion molecule. AB - PECAM-1 is a 130-120-kD integral membrane glycoprotein found on the surface of platelets, at endothelial intercellular junctions in culture, and on cells of myeloid lineage. Previous studies have shown that it is a member of the immunoglobulin gene superfamily and that antibodies against the bovine form of this protein (endoCAM) can inhibit endothelial cell-cell interactions. These data suggest that PECAM-1 may function as a vascular cell adhesion molecule. The function of this molecule has been further evaluated by transfecting cells with a full-length PECAM-1 cDNA. Transfected COS-7, mouse 3T3 and L cells expressed a 130-120-kD glycoprotein on their cell surface that reacted with anti-PECAM-1 polyclonal and monoclonal antibodies. COS-7 and 3T3 cell transfectants formed cell-cell junctions that were highly enriched in PECAM-1, reminiscent of its distribution at endothelial cell-cell borders. In contrast, this protein remained diffusely distributed within the plasma membrane of PECAM-1 transfected cells that were in contact with mock transfectants. Mouse L cells stably transfected with PECAM-1 demonstrated calcium-dependent aggregation that was inhibited by anti-PECAM antibodies. These results demonstrate that PECAM-1 mediates cell-cell adhesion and support the idea that it may be involved in some of the interactive events taking place during thrombosis, wound healing, and angiogenesis. PMID- 1874787 TI - EA-1, a novel adhesion molecule involved in the homing of progenitor T lymphocytes to the thymus. AB - The mouse progenitor T lymphocyte (pro-T) cell line FTF1 binds in vitro to thymus blood vessels, the thymic capsule, and liver from newborn mice. A mAb, EA-1, raised against an embryonic mouse endothelial cell line, blocked adhesion. The antibody also interfered with pro-T cell adhesion to a thymus-derived mouse endothelial cell line; it had no effect on the adhesion of mature T lymphocytes and myeloid cells. The antigen recognized by EA-1 is located on the vascular endothelium of various mouse tissues and absent on pro-T cells. EA-1 antibody precipitates molecules with apparent molecular weights of 110,000, 140,000, 160,000, and 200,000. Immunoclearing and binding-inhibition studies with antibodies against known adhesion molecules suggest that the EA-1 antigen is a novel adhesion molecule involved in colonization of the embryonic thymus by T cell progenitors. PMID- 1874788 TI - Evidence for thylakoid membrane fusion during zygote formation in Chlamydomonas reinhardtii. AB - To understand whether fusions of thylakoid membranes from the parental chloroplasts occurred during zygote formation in Chlamydomonas reinhardtii, we performed an ultrastructural analysis of the zygotes produced by crossing mutants lacking photosystem I or II protein complexes, in the absence of de novo chloroplast protein synthesis. Thylakoid membranes from each parent could be distinguished on thin sections due to their organization in "supergrana" in mutants lacking photosystem I centers, by freeze-fracturing due to the absence of most of the exoplasmic-face (EF) particles in mutants lacking photosystem II centers, by immunocytochemistry using antibodies directed against photosystem II subunits. We demonstrate that a fusion of the thylakoid membranes occurred during zygote formation approximately 15 h after mating. These fusions allowed a lateral redistribution of the thylakoid membrane proteins. These observations provide the structural basis for the restoration of photosynthetic electron flow in the mature zygote that we observed in fluorescence induction experiments. PMID- 1874789 TI - Organization of the sea urchin egg endoplasmic reticulum and its reorganization at fertilization. AB - The ER of eggs of the sea urchin Lytechinus pictus was stained by microinjecting a saturated solution of the fluorescent dicarbocyanine DiIC18(3) (DiI) in soybean oil; the dye spread from the oil drop into ER membranes throughout the egg but not into other organelles. Confocal microscopy revealed large cisternae extending throughout the interior of the egg and a tubular membrane network at the cortex. Since diffusion of DiI is confined to continuous bilayers, the spread of the dye supports the concept that the ER is a cell-wide, interconnected compartment. In time lapse observations, the internal cisternae were seen to be in continuous motion, while the cortical ER was stationary. After fertilization, the internal ER appeared to become more finely divided, beginning as a wave apparently coincident with the calcium wave and becoming most marked by 2-3 min. By 5-8 min the ER returned to an organization similar to that of the unfertilized egg. The cortical network also changed at fertilization; it became disrupted and eventually recovered. DiI labeling allowed continuous observations of the ER during pronuclear migration and mitosis. DiI-stained membranes accumulated in the region of the microtubule array surrounding the sperm nucleus and centriole (the sperm aster) as it migrated to the center of the egg; this accumulation persisted near the centrosomes and zygote nucleus throughout pronuclear fusion and the first two mitotic cycles. We have used a new method to observe the spatial and temporal organization of the ER in a living cell, and we have demonstrated a striking reorganization of the ER at fertilization. PMID- 1874790 TI - Desmin/vimentin intermediate filaments are dispensable for many aspects of myogenesis. AB - An expression vector was prepared containing a cDNA coding for a truncated version of the intermediate filament (IF) protein desmin. The encoded truncated desmin protein lacks a portion of the highly conserved alpha-helical rod region as well as the entire nonhelical carboxy-terminal domain. When transiently expressed in primary fibroblasts, or in differentiating postmitotic myoblasts and multinucleated myotubes, the truncated protein induces the complete dismantling of the preexisting vimentin or desmin/vimentin IF networks, respectively. Instead, in both cell types vimentin and desmin are packaged into hybrid spheroid bodies scattered throughout the cytoplasm. Despite the complete lack of intact IFs, myoblasts and myotubes expressing truncated desmin assemble and laterally align normal striated myofibrils and contract spontaneously in a manner indistinguishable from that of control myogenic cells. In older cultures the spheroid bodies shift from a longitudinal to a predominantly transverse orientation and loosely align along the I-Z-I-regions of striated myofibrils (Bennett, G.S., S. Fellini, Y. Toyama, and H. Holtzer. 1979. J. Cell Biol. 82:577 584), analogous to the translocation of intact desmin/vimentin IFs in control muscle. These results suggest the need for a critical reexamination of currently held concepts regarding the functions of desmin IFs during myogenesis. PMID- 1874792 TI - Microtubule dynamics and microtubule caps: a time-resolved cryo-electron microscopy study. AB - Microtubules display the unique property of dynamic instability characterized by phase changes between growth and shrinkage, even in constant environmental conditions. The phases can be synchronized, leading to bulk oscillations of microtubules. To study the structural basis of dynamic instability we have examined growing, shrinking, and oscillating microtubules by time-resolved cryo EM. In particular we have addressed three questions which are currently a matter of debate: (a) What is the relationship between microtubules, tubulin subunits, and tubulin oligomers in microtubule dynamics?; (b) How do microtubules shrink? By release of subunits or via oligomers?; and (c) Is there a conformational change at microtubule ends during the transitions from growth to shrinkage and vice versa? The results show that (a) oscillating microtubules coexist with a substantial fraction of oligomers, even at a maximum of microtubule assembly; (b) microtubules disassemble primarily into oligomers; and (c) the ends of growing microtubules have straight protofilaments, shrinking microtubules have protofilaments coiled inside out. This is interpreted as a transition from a tense to a relaxed conformation which could be used to perform work, as suggested by some models of poleward chromosome movement during anaphase. PMID- 1874791 TI - Microinjection of the catalytic fragment of myosin light chain kinase into dividing cells: effects on mitosis and cytokinesis. AB - Myosin light chain kinase (MLCK) is thought to regulate the contractile activity in smooth and non-muscle cells, and may play an important role in controlling the reorganization of the actin-myosin cytoskeleton during cell division. To test this hypothesis we have microinjected the 61-kD catalytic fragment of MLCK into mitotic cells, and examined the effects of unregulated MLCK activity on cell division. The microinjection of active 61 kD causes both a significant delay in the transit time from nuclear envelope breakdown to anaphase onset, and an increase in motile surface activity during and after metaphase. Control experiments with intact MLCK or with inactive catalytic fragment suggest that these effects are specifically induced by the unregulated myosin light chain kinase activity. Immunofluorescence analysis suggests that delays in mitosis are coupled to disruptions of spindle structures, while increased surface motility may be related to changes in the organization of actin and myosin at the cell cortex. Most importantly, despite the expression of strong phenotypes, 61 kD injected cells still form functional cleavage furrows that progress through cytokinesis at rates identical to those of control cells. Together, these results suggest that the activity of MLCK can affect mitosis and cortical activities, however additional control mechanisms are likely involved in the regulation of cytokinesis. PMID- 1874793 TI - The role of solation-contraction coupling in regulating stress fiber dynamics in nonmuscle cells. AB - Serum-deprived Swiss 3T3 fibroblasts constitutively form stress fibers at their edges. These fibers move centripetally towards the perinuclear region where they disassemble. Serum stimulation causes shortening of fibers in a manner suggesting active actin-myosin-based contraction (Giuliano, K.A. and D.L. Taylor. 1990. Cell Motil. and Cytoskeleton. 16:14-21). To elucidated the role of actin-based gel structure in these movements, we examined the effects of disrupting actin organization with cytochalasin. Serum-deprived fibroblasts were microinjected with rhodamine analogs of actin or myosin II and fiber dynamics were monitored with a multimode light microscope workstation using video-enhanced contrast and fluorescence modes. When cells were perfused with greater than or equal to 3 microM cytochalasin B or 0.5 microM cytochalasin D, formation and transport of stress fibers were reversibly inhibited, and rapid and immediate shortening of existing fibers was induced. Quantification of actin and myosin II fluorescence associated with individual shortening fibers demonstrated that fluorescence per length of fiber increased for both components, suggesting sliding filament contraction. However, there was also a net loss of both actin and myosin II from fibers as they shortened, indicating a self-destructive process. Loss of material from fibers coupled with increased overlap of actin and myosin II remaining in the fibers suggested that contraction could be induced not only by increasing the force exerted by contractile motors, but also by decreasing gel structure through partial solation. Finally, cytochalasin accelerated contraction of actin-myosin based gels reconstituted from purified proteins in the absence of myosin-based regulation, further supporting solation-contraction coupling as a possible mechanism for modulating cytoplasmic contractility (Taylor, D.L. and M. Fechheimer. 1982. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 299:185-197). PMID- 1874794 TI - Growth factors and wound repair. PMID- 1874795 TI - Growth factors. PMID- 1874796 TI - Endothelium-derived relaxing and contracting factors. AB - Key discoveries in the past decade revealed that the endothelium can modulate the tone of underlying vascular smooth muscle by the synthesis/release of potent vasorelaxant (endothelium-derived relaxing factors; EDRF) and vasoconstrictor substances (endothelium-derived contracting factors; EDCF). It has become evident that the synthesis and release of these substances contribute to the multitude of physiological functions the vascular endothelium performs. Accumulating evidence suggests that at least one of the EDRFs is identical with nitric oxide (NO) or a labile nitroso compound, which is produced from L-arginine by an NADPH- and Ca(2+)-dependent enzyme, arginine oxidase. The existence of more than one chemically distinct EDRF has been proposed, including an endothelium-derived hyperpolarizing factor (EDHF). The target of EDRF (NO) is soluble guanylate cyclase (increase in cyclic GMP) while EDHF appears to activate a K(+)-channel in vascular smooth muscle. Recent data suggest that muscarinic receptor subtypes selectively mediate the release of EDRF(NO) (M2) and EDHF (M1). EDRF(NO) affects not only the underlying vascular smooth muscle, but also platelets, inhibiting their aggregation and adhesion to the endothelium. The antiaggregatory effect of EDRF is synergistic with prostacyclin, so their combined release may represent a physiological mechanism aimed at preventing thrombus formation. An additional proposed biological function of EDRF(NO) is cytoprotection by virtue of scavenging superoxide radicals. The endothelium can also mediate vasoconstriction by the release of a variety of endothelium-derived contracting factors (EDCF). Other than the unique peptide endothelin, the nature of EDCFs has not yet been firmly established. Autoregulation of cerebral and renal blood flow and hypoxic pulmonary vasoconstriction may represent the physiological role of endothelium dependent vasoconstriction. Growing evidence indicates that the endothelium can serve as a unique mechanoreceptor, sensing and transducing physical stimuli (e.g., shear forces, pressure) into changes in vascular tone by the release of EDRFs or EDCFs. In physiological states, a delicate balance exists between endothelium-derived vasodilators and vasoconstrictors. Alterations in this balance can result in local (vasospasm) and generalized (hypertension) increase in vascular tone and also in facilitated thrombus formation. Endothelial dysfunction may also contribute to the pathophysiology of angiopathies associated with hypercholesterolemia and atherosclerosis. PMID- 1874797 TI - Genetics of the malignant progression of astrocytoma. AB - The tendency of human cancers to progress towards a more malignant state over time is a well described biological phenomenon. Recent investigations elucidating the genetic nature of malignancy and the possible mechanisms responsible for this evolution have suggested that a sequential pathway may exist whereby a cell population accumulates a nested set of genetic aberrations which endow it with the ability to overwhelm other populations and dominate the tumor. Human astrocytomas are a dramatic case in point, where specific genetic events of amplification and deletion are seemingly related to the stages of malignancy. The identification of these aberrations represents the first stage in the dissection of the temporal process of this cancer. Its augmentation with functional analyses will likely allow a fuller genetic description of in vivo transformation. PMID- 1874798 TI - Implications and concepts of polyamine-nucleic acid interactions. AB - Modeling, x-ray diffraction, and solution studies have contributed to the understanding of interactions between polyamines and nucleic acids. Polyamines stabilize a variety of unusual DNA structures and conformations in vitro, including both the left-handed Z and the right-handed A DNA. In addition, polyamines condense DNA and may be important in bending specific sequences. Investigations into the mechanisms of these effects provide support for both specific and nonspecific interactions between polyamines and DNA. Although exact relationships between the binding of polyamines and conformational changes in nucleic acids are still being clarified, polyamines remain important candidates for regulators of DNA conformation in vivo. PMID- 1874799 TI - Isolation of heparan sulfate proteoglycan from beneath the monolayers of rat hepatocytes and its binding to type IV collagen. AB - Primary cultures of rat hepatocytes maintained as monolayer in a serum-free medium synthesise and secrete sulphated proteoglycans. Nearly 5% of the total 35(S)-sulphated material was obtained in a soluble form from beneath the cell layer. A shift in gel filtration pattern on beta-elimination with alkali suggested that it is a sulphated proteoglycan. On ion exchange chromatography over Dowex AG 1 x 2, the major fraction was eluted with 1.25 M NaCl. Further, nearly 80% of the 35(S)-labeled material was susceptible to nitrous acid degradation and more than 90% of the material was resistant to chondroitinase ABC digestion suggesting that it is predominantly a heparan sulphate proteoglycan (HSPG). Since HSPG is a major component of basement membrane, its binding with collagen was studied by a solid phase binding assay. About 75% of the 35(S) HSPG bound to wells coated with type IV collagen whereas only about 20% bound to type I collagen at physiological pH. Binding to collagen IV was reduced by about 50% when free GAG chains were used indicating that the protein core is also involved in interaction with the collagen. These results indicate the possible role of this basal extracellular heparan sulphate proteoglycan in the basal lamina formation. PMID- 1874800 TI - Na(+)-dependent, active nucleoside transport in S49 mouse lymphoma cells and loss in AE-1 mutant deficient in facilitated nucleoside transport. AB - S49 murine lymphoma cells were examined for expression of various nucleoside transport systems using a non-metabolized nucleoside, formycin B, as substrate. Nitrobenzylthioinosine (NBTI)-sensitive, facilitated transport was the primary nucleoside transport system of the cells. The cells also expressed very low levels of NBTI-resistant, facilitated nucleoside transport as well as of Na(+) dependent, concentrative formycin B transport. Concentrative transport was specific for uridine and purine nucleosides, just as the concentrative nucleoside transporters of other mouse and rat cells. A nucleoside transport mutant of S49 cells, AE-1, lacked both the NBTI-sensitive, facilitated and Na(+)-dependent, concentrative formycin B transport activity, but Na(+)-dependent, concentrative transport of alpha-aminoisobutyrate was not affected. PMID- 1874801 TI - Novel immunomodulators with pronounced in vivo effects caused by stimulation of cytokine release. AB - Beta-1,3-D-polyglucose derivatives protect mice against otherwise lethal bacterial infections. This protective effect has been considered to be mediated through mononuclear phagocytes. By using radioactive labelling, we localized the beta-1,3-D-polyglucose derivatized microbeads (GDM) during the period following injection. The GDM was recovered mainly in the milky spots of the omentum. In animals treated with GDM, the total white cell number was significantly increased in peritoneal fluid of mice before and after challenge with E. coli. Bacterial counts in peritoneal fluid of GDM treated animals declined to zero after 24 h. In untreated animals there was a slight increase in bacterial counts until the animals died after about 12 h. Mouse peritoneal macrophages stimulated with GDM released significant amounts of IL-1 and PGE2. There was no significant release of TNF. Levels of IL-1 and PGE2 in peritoneal fluid increased significantly during the first 48 h after treatment with GDM. There was no increase of levels of TNF. After challenge with E. coli, the levels of IL-1, TNF, and PGE2 were significantly lower compared with control animals. In untreated animals the levels of IL-1 and TNF remained elevated until the animals died after about 12 h. These studies demonstrate that the raised levels of arachidonic acid metabolites after pretreatment with GDM or AG seems to inhibit the otherwise lethal elevation of IL-1 and TNF in body fluids which is seen in untreated animals. PMID- 1874802 TI - Tumor necrosis factor stimulates ornithine decarboxylase activity in human fibroblasts and tumor target cells. AB - The activity of the polyamine biosynthetic enzyme, ornithine decarboxylase (ODC), has been shown to be rapidly modulated by a variety of growth regulatory molecules. In this report the effect of the growth modulatory peptide, tumor necrosis factor, on ODC activity was examined on two cell lines which express equivalent TNF binding properties, but differ in their growth response when exposed to this factor. TNF treatment of WI-38 fibroblasts stimulated both their growth and induced ODC activity 5-10-fold when measured 6-24 h after TNF incubation. TNF induced cytotoxicity in ME-180 cervical carcinoma cells and, interestingly, stimulated both ODC activity (3-6-fold) and putrescine accumulation when measured prior to the onset of cytotoxicity. Induction of ODC was TNF concentration-dependent and paralleled the concentration-dependency for cytotoxicity. Based upon studies with cycloheximide, de novo protein biosynthesis was required for TNF-mediated ODC induction in ME-180 cells. The effects of other growth inhibitory peptides and growth factors were analyzed for their combined effect on ODC activity in TNF-treated or untreated ME-180 cells. Interferon gamma treatment had no significant effect on basal ODC activity but inhibited TNF mediated ODC induction by approximately 50%. EGF treatment resulted in a potent stimulation of ODC activity which was not affected by TNF pre-treatment or coadministration on ME-180 cells. These results suggest that TNF has properties which are similar to those of a growth factor and distinct from those of other growth inhibitory peptides. The early growth factor-like actions of TNF occur on both normal fibroblasts and some tumor cells and evidence suggests that these effects are antagonistic to the antiproliferative effects of TNF. PMID- 1874803 TI - Cellular response to double-stranded RNA. AB - The study of double-stranded RNA (dsRNA) encompasses a variety of fields. Basic research in this area has contributed to a greater mechanistic understanding of gene induction, tumor cell growth arrest, the establishment of antiviral states, and immunomodulation. Because of the possible clinical value of these molecules, physicians are now exploring the use of synthetic dsRNA to treat patients with cancer, HIV-1 disease, and immune dysfunction. Continued studies of the mechanisms of action of dsRNA are likely to suggest an even wider scope of clinical applications. PMID- 1874804 TI - Measurement of human cerebral blood flow with [15O]butanol and positron emission tomography. AB - Although H2(15)O is widely used for CBF measurement by positron tomography, it underestimates CBF, especially at elevated flow rates. Several tracers, including butanol, overcome this problem, but the short half-life of 15O provides advantages that cause water to remain the tracer of choice. We report the first use and evaluation of 15O-labeled butanol for CBF measurement. Flow measurements made in a similar fashion with water and butanol at 10-min intervals were compared in normal volunteers under resting and hypercapnic conditions. Regional analysis showed good agreement between the tracers at low flows, and significant underestimation of flow by water relative to butanol in regions of elevated flow. The observed relationship between the tracers and the curve-fitted permeability surface area product for water (133 ml.100 g-1.min-1) follow the known relationship between water and true flow. These observations indicate that [15O] butanol provided accurate measurements of human regional CBF under conditions of elevated perfusion. We conclude that butanol is a convenient and accurate method for routine CBF determination by positron emission tomography. PMID- 1874805 TI - Distribution and kinetics of 3-O-methyl-6-[18F]fluoro-L-dopa in the rhesus monkey brain. AB - Most attempts to model accurately [18F]-DOPA imaging of the dopamine system are based on the assumptions that its main peripheral metabolite, 3-O-methyl-6 [18F]fluoro-L-DOPA ([18F]3-OM-DOPA), crosses the blood-brain barrier but is present as a homogenous distribution throughout the brain, in part because it is not converted into [18F]DOPA in significant quantities. These assumptions were based mainly on data in rodents. Little information is available in the primate. To verify the accuracy of the above assumptions, we administered 18F-labeled 3-OM DOPA to normal rhesus monkeys and animals with lesions of the DA nigrostriatal system. No selective 18F regional accumulation in brain was apparent in normal or lesioned animals. The plasma metabolite analysis revealed that only the negatively charged metabolites (e.g., sulfated conjugates) that do not cross the blood-brain barrier were found in significant quantities in the plasma. A one compartment, three-parameter model was adequate to describe the kinetics of [18F]3-OM-DOPA. In conclusion, assumptions concerning [18F]3-OM-DOPA's behavior in brain appear acceptable for [18F]DOPA modeling purposes. PMID- 1874806 TI - Differentiation of radioligand delivery and binding in the brain: validation of a two-compartment model for [11C]flumazenil. AB - We recently developed a two-compartment, two-parameter tracer kinetic model to estimate the in vivo ligand transport rate (K1) and distribution volume (DV) for the benzodiazepine antagonist [11C]flumazenil (FMZ) as measured by positron emission tomography (PET). The aim of the present study was to validate that this simplified model provides a stable measure of regional benzodiazepine receptor availability even when ligand delivery is altered. Six young normal volunteers underwent two PET studies subsequent to intravenous injections of [11C]FMZ. Each FMZ study was immediately preceded by measurements of CBF following injection of [15O]water. One set of scans (water/FMZ) was acquired under resting conditions and the other set during audiovisual stimulation. Six additional volunteers underwent two FMZ studies under identical resting conditions. Parametric images were analyzed and a comparison of test-retest studies in the stimulation group revealed a significant increase of CBF and K1 of FMZ in the occipital cortex evoked by visual activation, whereas no regional changes were noted for the DV of FMZ. No significant changes were noted for either K1 or DV of FMZ when comparing studies in the rest-rest setting. The results indicate that the use of a simple two-compartment model for the tracer kinetic analysis of [11C]FMZ makes it possible to separate high-affinity binding from altered radio-ligand delivery to the human brain. PMID- 1874807 TI - Ischemic thresholds of cerebral protein synthesis and energy state following middle cerebral artery occlusion in rat. AB - The ischemic threshold of protein synthesis and energy state was determined 1, 6, and 12 h after middle cerebral artery (MCA) occlusion in rats. Local blood flow and amino acid incorporation were measured by double tracer autoradiography, and local ATP content by substrate-induced bioluminescence. The various images were evaluated at the striatal level in cerebral cortex by scanning with a microdensitometer with 75 microns resolution. Each 75 x 75 microns digitized image pixel was then converted into the appropriate units of either protein synthesis, ATP content, or blood flow. The ischemic threshold was defined as the flow rate at which 50% of pixels exhibited complete metabolic suppression. One hour after MCA occlusion, the threshold of protein synthesis was 55.3 +/- 12.0 ml 100 g-1 min-1 and that of energy failure was 18.5 +/- 9.8 ml 100 g-1 min-1. After 6 and 12 h of MCA occlusion, the threshold of protein synthesis did not change (52.0 +/- 9.6 and 56.0 +/- 6.5 ml 100 g-1 min-1, respectively) but the threshold of energy failure increased significantly at 12 h following MCA occlusion to 31.9 +/- 9.7 ml 100 g-1 min-1 (p less than 0.05 compared to 1 h ATP threshold value; all values are mean +/- SD). In focal cerebral ischemia, therefore, the threshold of energy failure gradually approached that of protein synthesis. Our results suggest that with increasing duration of ischemia, survival of brain tissue is determined by the high threshold of persisting inhibition of protein synthesis and not by the much lower one of acute energy failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874808 TI - In vivo binding of nimodipine in the brain: I. The effect of focal cerebral ischemia. AB - We report the regional variation in [3H]nimodipine binding in vivo during focal cerebral ischemia. After intravenous injection, 30 min of circulation of [3H]nimodipine was sufficient to establish a secular equilibrium of distribution in the brain. Rats sustained left middle cerebral and common carotid artery occlusions for 5 min, and 4, 24, and 48 h (n greater than or equal to 6 epr group). They were decapitated 30 min after injection of 250 microCi of [3H]nimodipine and their brains were submitted to autoradiography. The concentrations of [3H]nimodipine in plasma and brain structures, corrected for metabolism of nimodipine, were used to calculate the regional volumes of distribution (V) in the ischemic left (L) and control right (R) hemispheres. Log (VL/VR) was then defined as the group mean of the logarithms of the left-to-right ratio of V of [3H]nimodipine. In the lateral caudate, binding of [3H]nimodipine on the ischemic side was highest within 5 min of occlusion. Log (VL/VR) in this region for the combined sham-operated and normal control rats and those after 5 min and 4 and 24 h of ischemia were -0.014 +/- 0.025, 0.137 +/- 0.056*, -0.201 +/ 0.367, and -0.049 +/- 0.370 (mean +/- SD, *represents p less than 0.01 compared with controls). By contrast, in the superior frontal cortex, values for log (VL/VR) in the same sequence were -0.016 +/- 0.025, 0.028 +/- 0.056, 0.284 +/- 0.228*, and 0.224 +/- 0.069*, thus showing a significant rise in [3H]nimodipine binding only at 4 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874809 TI - In vivo binding of nimodipine in the brain: II. Binding kinetics in focal cerebral ischemia. AB - We report the binding characteristics of [3H]nimodipine to normal and ischemic brain in vivo. We used the 1,4-dihydropyridine, nimodipine, to label the L-type voltage-sensitive calcium channel in focal cerebral ischemia after occlusion of both the middle cerebral and ipsilateral common carotid arteries in rats. Varying concentrations of [3H]nimodipine were infused 3.5 h after the onset of ischemia and circulated for 30 min before the brain was obtained for autoradiography and determination of regional nimodipine content. In separate sets of experiments, the metabolites of nimodipine were determined and the conditions for equilibrium of nimodipine distribution were established. Increased nimodipine uptake was observed in ischemic regions. This increased binding was saturable and specific with an affinity constant, KD, of 0.45 nM and a maximal regional binding capacity, Bmax, ranging from 3.1 to 10.9 pmol/g. Only binding to ischemic tissue was specific and saturable whereas that in nonischemic tissue was nonspecific. In vivo binding of nimodipine may be used to identify cell membrane depolarization and calcium channel activation in focal cerebral ischemia. PMID- 1874810 TI - Reversible focal ischemia in the rat: effects of halothane, isoflurane, and methohexital anesthesia. AB - Barbiturates and the volatile anesthetic isoflurane reduce CMR to similar values. If the mechanism of barbiturate protection against focal ischemic injury is due to a reduction in cellular energy requirements, then isoflurane should similarly reduce ischemic injury. To evaluate this, spontaneously hypertensive rats underwent 2 h of reversible middle cerebral artery occlusion (MCAO) while receiving deep methohexital, isoflurane, or halothane anesthesia. Ninety-six hours postischemia, neurologic deficits were present but without a difference between groups. Mean +/- SD infarct volume, as assessed by triphenyl tetrazolium chloride staining and computerized planimetry, was significantly less in the methohexital group (n = 8; 166 +/- 74 mm3) than in either the halothane (n = 9; 249 +/- 71 mm3; p less than 0.04) or the isoflurane (n = 9; 243 +/- 62 mm3; p less than 0.03) groups. One possible explanation for the lack of protective effect for isoflurane might be related to its vasodilative properties, which could result in a cerebral vascular steal. To examine this possibility, rats anesthetized with methohexital or isoflurane underwent autoradiographic determination of CBF with or without MCAO. In isoflurane-anesthetized sham rats (n = 5; no ischemia), CBF was approximately three times greater than in methohexital-treated (n = 5) sham rats. During ischemia, although a regional reduction in flow was noted in both anesthetic groups, mean flow remained greater in the isoflurane group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874811 TI - Effects of dextromethorphan on regional cerebral blood flow in focal cerebral ischemia. AB - Dextromethorphan (DM), a noncompetitive NMDA antagonist, has been demonstrated to reduce ischemic neuronal damage and edema, but DM's influence on cerebral blood flow has not been extensively studied. In this investigation, it is shown that DM has significant effects on regional cerebral blood flow (rCBF) patterns in a rabbit model of focal cerebral ischemia. rCBF was measured using radioactive microspheres following a 1 h permanent occlusion of the left internal carotid, anterior cerebral, and middle cerebral arteries in rabbits. Somatosensory evoked potentials (SEPs) were used to assess the degree of ischemia; only animals where SEPs were completely abolished were used for a frequency distribution analysis of rCBF. It was found that there were significantly more regions with lower flows in animals treated with normal saline (NS) (n = 7) compared to animals treated with DM (n = 7) (p less than 0.05, ipsilateral left side; p less than 0.001, contralateral right side). The frequency distribution medians were 27.5 ml 100 g 1 min-1 (left) and 70.0 ml 100 g-1 min-1 (right) in the NS group vs. 34.5 ml 100 g-1 min-1 (left) and 80.5 ml 100 g-1 min-1 (right) in the DM group. The left and right hemispheric regional means were 29.4 +/- 20 and 74.3 +/- 23 ml 100 g-1 min 1, respectively, in the NS group vs. 34.4 +/- 16 and 91.0 +/- 28 ml 100 g-1 min 1, respectively, in the DM group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874812 TI - Electrical stimulation of cerebellar fastigial nucleus reduces ischemic infarction elicited by middle cerebral artery occlusion in rat. AB - Electrical stimulation of the cerebellar fastigial nucleus (FN) globally and profoundly increases cerebral blood flow via a cholinergic mechanism. In cerebral cortex, the vasodilation is unassociated with alterations in cerebral glucose utilization, a condition favoring protection against cerebral ischemia. We sought to determine whether FN stimulation would modify the size of the focal ischemic infarction resulting from occlusion of the middle cerebral artery (MCA). The MCA was occluded in anesthetized rats of the spontaneously hypertensive (SHR) or Sprague-Dawley (SD) strains with or without 1 h of electrical stimulation of the FN. Twenty-four hours later, rats were killed and the volume of the infarction established in thionin-stained sections. in SHRs, FN stimulation reduced by 40% the well-established cortical and partially subcortical infarctions elicited by occlusion of the MCA (from 186 +/- 35.2 to 113 +/- 47.1 mm3, mean +/- SD, n = 15; p less than 0.001). The zone of retrieval was anatomically constant, consisting of a rim of cortex dorsal and ventral to the infarction and medially within the thalamus and striatum corresponding to the penumbral zone described by others. The effect was comparable in rats of the SD strain having smaller infarctions. The effect of FN stimulation appears to be selective for the FN system in that it is not evoked by stimulation of the dentate nucleus and is blocked by systemic administration of atropine (1.0 mg/kg). We conclude that excitation of an intrinsic system in brain represented in the rostral FN has the capacity to reduce substantially an ischemic infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874813 TI - Delayed neuronal death is induced without postischemic hyperexcitability: continuous multiple-unit recording from ischemic CA1 neurons. AB - It has been proposed that neuronal hyperexcitability during postischemic chronic stage mediates delayed neuronal death in the hippocampal CA1 region. In the present study, multiple-unit spike discharges were continuously recorded from hippocampal CA1 neurons of the awake Mongolian gerbil for 5 days after 5 min of ischemia. Before ischemia, CA1 neurons showed burst-like spike discharges (so called complex spikes). Spike discharges disappeared 8-40 s after the onset of 5 min ischemia and reappeared 5-30 min after recirculation. The frequency of discharges gradually increased but did not return to the preischemic level. The amplitude of the spike discharges was smaller than that recorded before ischemia and the number of spikes composing the burst-like discharges diminished. CA1 neurons did not show any hyperexcitability for 5 days. However, histological examinations revealed widespread neuronal death in the CA1 region. These results indicate that the delayed neuronal death in the hippocampal CA1 region is induced without postischemic neuronal hyperexcitability. PMID- 1874814 TI - Ischemia-reperfusion does not affect reactivity of isolated canine basilar artery. AB - The effect of ischemia-reperfusion on endothelium-dependent relaxations and reactivity of vascular smooth-muscle cells was studied in rings of basilar arteries obtained from six dogs exposed to 12 min of complete global cerebral ischemia followed by 100 min of reperfusion. Three sham-operated control dogs served as controls. Ischemia was induced either by an increase in intracranial pressure or by aortic occlusion. The rings were suspended for isometric tension recording in physiological salt solution. Ischemia-reperfusion did not affect endothelium-dependent relaxations to vasopressin and bradykinin. In rings without endothelium relaxations to sodium nitroprusside, molsidomine (SIN-1), and papaverine as well as contractions to 5-hydroxytryptamine and KCl were preserved. These results demonstrate that in large canine cerebral arteries, ischemia reperfusion of these durations does not affect relaxations mediated by activation of endothelium or direct relaxations and contractions of vascular smooth-muscle cells. PMID- 1874815 TI - Cerebral blood flow and oxygen consumption in cortical spreading depression. AB - We determined the effects of spreading depression on local cerebral O2 supply, oxygenation, and O2 consumption in the anesthetized rat. Spreading depression was induced by application of 0.5 M KCl to the frontal cortex. Regional cerebral blood flow was determined with [14C]iodoantipyrine and regional O2 extraction was determined microspectrophotometrically. The passage of the spreading depression wave was determined with a multiprobe assembly that recorded NADH redox state (surface fluorometry), extracellular K+ activity, and DC steady potential (surface minielectrodes). As the wave of spreading depression passed, there was an increase in extracellular K+ and a decrease in NADH. Cerebral blood flow was significantly increased (120 +/- 51 ml/min/100 g, mean +/- SD) during the wave as compared with other regions. In the affected cortex, blood flow was not different from that in the contralateral cortex (69 +/- 28 ml/min/100 g) either before or after the wave of spreading depression passed. Arterial and venous O2 saturation were unaffected by the wave and the histogram of O2 saturations of examined veins followed a similar normal distribution in all regions. Oxygen extraction was not altered by the wave of spreading depression. Oxygen consumption was significantly increased during the wave to 7.4 +/- 3.7 ml O2/min/100 g compared with the contralateral cortex (5.1 +/- 2.6 ml/min/100 g) and other regions. It can be concluded that spreading depression caused an increase in cerebral O2 consumption that was adequately matched by an increase in local blood flow. Oxygen delivery was not limited during spreading depression and its effects were quickly over as evidenced by the lack of alteration in oxygenation after the wave of spreading depression passed. PMID- 1874816 TI - Cerebral oxygen metabolism after aneurysmal subarachnoid hemorrhage. AB - Previous studies of cerebral oxygen metabolism and extraction in patients with subarachnoid hemorrhage (SAH) have yielded conflicting results. We used positron emission tomography (PET) to measure the regional cerebral metabolic rate for oxygen (rCMRO2), oxygen extraction fraction (rOEF), and cerebral blood flow (rCBF) 16 times in 11 patients with aneurysmal SAH. All studies were performed preoperatively; no patient had hydrocephalus or intracerebral hematoma on brain CT. Eight patients with no arteriographic vasospasm who were studied on days 1-4 post-SAH had a significant 25% reduction in global CMRO2 compared to age-matched controls, and no significant change in global OEF, suggesting a primary reduction in CMRO2 caused by SAH. Four patients studied seven times during arteriographic vasospasm had significantly increased rOEF with unchanged CMRO2 in arterial territories affected by arteriographic vasospasm compared to territories without vasospasm, indicative of cerebral ischemia without infarction. No brain regions studied with PET were infarcted on follow-up CT. We conclude that the initial aneurysm rupture produces a primary reduction in CMRO2, and that subsequent vasospasm causes ischemia. PMID- 1874817 TI - Effects of focal cortical freezing lesion on regional energy metabolism. AB - Freezing lesions have been shown to cause a depression in glucose use, particularly in cortical areas of the brain ipsilateral to the lesion, and this effect was interpreted to be caused by a depressed functional activity in these regions. The metabolic status of the affected areas has not been previously examined and could be a factor in the observed changes in local CMRglc. In frozen cut and dried sections taken from brains 3 days after freeze lesioning, discrete pieces of the median and lateral parietal cortex, striatum, hippocampus, and hypothalamus were dissected and analyzed for ATP, P-creatine, glucose, and lactate. CMRglc measurements were also made in the same animals. The concentrations of the four metabolites were significantly increased in the lesioned hemisphere, with the most predominant effects observed in the cortical areas that exhibited the greatest depression in CMRglc. The enriched metabolite profile, particularly in the cortical areas, is consistent with the hypothesis that decreased glucose use in the traumatized brain is caused by diminished need rather than by decreased supply of energy. Because the lumped constant in the operational equation of the deoxyglucose method for determination of CMRglc is a function of brain glucose content and decreases gradually in hyperglycemia, the degree of metabolic depression in cortical areas of lesioned hemisphere probably have been somewhat overestimated in this and previous publications. However, provisionally recalculated local CMRglc in the lesioned hemisphere remain significantly lower than in the contralateral hemisphere and in the normal brain. PMID- 1874818 TI - Role of thalamus and white matter in cognitive outcome after head injury. AB - Local CBF (LCBF) and local partition coefficients (L lambda) were measured by xenon-enhanced computed tomography among 15 patients with remote cerebral trauma resulting from severe head injury. Results were compared with similar measures among age-matched normal volunteers (N = 20). The patients were divided into two groups according to different outcomes based on serial cognitive testing: Group I (N = 10) improved but Group D (N = 5) deteriorated throughout a mean interval of 10 years of follow-up. Initial LCBF measurements were performed at mean intervals of 6.8 years after injury. Cortical LCBF values were decreased in frontal (p less than 0.01) and temporal (p less than 0.05) regions among both groups, but only in Group D were flow values decreased in putamen and thalamus (p less than 0.05). L lambda values were reduced in frontotemporal cortex among both groups but in the thalamus only among Group D (p less than 0.05). Mean white matter flow values were normal in Group I but were reduced in Group D (p less than 0.05). Mean partition coefficients for white matter were reduced in both groups (p less than 0.01) but were lower in Group D (p less than 0.05). Reduced perfusion of frontotemporal gray matter is consonant with neuropathological reports following severe brain trauma of neuronal atrophy, gliosis, and infarction affecting these regions. Group comparisons between patients who cognitively improved versus those that deteriorated demonstrate an association between reductions of CBF in putamen, thalamus and subcortical white matter and impaired cognition after severe head injury. PMID- 1874819 TI - Simultaneous and continuous measurement of choroid plexus blood flow and cerebrospinal fluid production: effects of vasoactive intestinal polypeptide. AB - Using laser-Doppler flowmetry during ventriculocisternal perfusion with inulin [14C]carboxylic acid, choroid plexus blood flow (CPBF) and CSF production were measured simultaneously in rats during periods of 3 h. Blood flow and CSF production decreased only slightly during control experiments. The effect of vasoactive intestinal polypeptide (VIP) was studied at different concentrations of the peptide given either intraventricularly or intravenously. Intraventricular administration of VIP (10(-9) or 10(-7) M) resulted in a decrease in CSF production of up to 30%, while CPBF increased by 20%, also demonstrating that CSF production and blood flow are not directly coupled in the choroid plexus. When infused intravenously, VIP (10 or 100 pmol/kg/min) increased CPBF, an effect partly antagonized at higher concentrations owing to a VIP-induced systemic hypotension. No effect of VIP on CSF production could be seen with intravenous administration. PMID- 1874820 TI - Periendothelial acetylcholine synthesis and release in bovine cerebral cortex capillaries. AB - Choline acetyltransferase (ChAT) activity is present in isolated cerebral capillaries, where it has been considered to be a marker for perivascular cholinergic nerve terminals. However, ChAT-like immunoreactivity has been visualized in endothelial cells. This finding raised the possibility that at least part of the biochemically detected ChAT has a nonneuronal origin. To evaluate the relative contribution of endothelial cells and nerve fibers to the total acetylcholine (ACh)-synthesizing capacity of cerebral capillaries, ChAT activity and ACh release were measured in capillaries and in purified endothelial cells isolated from bovine cerebral cortex. Isolated capillaries showed ChAT activity, which was inhibited by 2-benzoylethyl trimethylammonium to the same extent as cerebral ChAT. When preincubated with [3H]choline, these capillaries presented a calcium-dependent enhancement in tritium release upon electrical field stimulation. Purified endothelial cells had minor ChAT activity and lacked the ability to release tritium in response to electrical stimulation, although the endothelial markers alkaline phosphatase, gamma-glutamyltranspeptidase, and 1,1'-dioctadecyl-1,3,3',3'-tetramethyl-iodocarbocyanide perchlorate-labeled acetylated low-density lipoprotein uptake were fully preserved. These data indicate that, within isolated cerebral capillaries, ACh is synthesized and released by a periendothelial structure. The fact that ACh release is provoked by electrical stimulation and by a calcium-dependent mechanism strongly suggests that cerebrovascular ACh has a neuronal origin. PMID- 1874821 TI - Choline acetyltransferase activity associated with cerebral cortical microvessels does not originate in basal forebrain neurons. AB - Cerebral cortical microvessels are innervated by cholinergic fibers that are probably involved in the regulation of local cerebral blood flow and blood-brain barrier permeability. The possibility exists that the cholinergic terminals associated with the cortical microvasculature belong to neurons from the nucleus basalis magnocellularis (NBM), where 70% of the cortical cholinergic projections originate. To test this hypothesis, ibotenic acid (25 nmol) was injected unilaterally in the NBM in rats, and 14 days later, choline acetyltransferase (ChAT) activity was measured in the frontoparietal cortex and in a blood vessel fraction isolated from this region. Lesions of the NBM resulted in a 50% decrease of cortical ChAT as compared with control or sham-operated hemispheres; however, no changes were observed in the ChAT activity associated with cortical microvessels. These results indicate that, in rat cerebral cortex, the perivascular cholinergic terminals do not originate in the basal forebrain. PMID- 1874822 TI - Flow estimation using ultrasound imaging (color M-mode) and computer postprocessing. AB - We have developed a method to calculate flow noninvasively in blood vessels using color Motion-mode (M-mode) and computer postprocessing. The velocity of each point in the cross-sectional area of the vessel was found from the color M-mode recording by correcting for angle both distances and velocities and by assuming a symmetrical circular velocity field. Volume flow was then found by integrating the velocity field at 5-ms intervals through the cardiac cycle. In a cardiovascular hydromechanical model, a correlation of 0.99 and p value of less than 0.001 were found between estimated and measured flow in the model (n = 8). In 20 healthy individuals, we made 31 investigations in the common carotid (CCA), internal carotid (ICA), and external carotid (ECA) artery, comparing flow in the CCA with the added flow in the ICA and ECA. The values (CCA versus ICA + ECA) correlated with r = 0.91 and p less than 0.01. Repeated investigations (n = 8) in one individual gave flow estimates of 495 +/- 50 ml/min in the CCA, 304 +/- 45 ml/min in the ICA, and 165 +/- 37 ml/min in the ECA (means +/- SD). This article shows that this system can make accurate estimation of blood flow to the brain noninvasively. PMID- 1874823 TI - A database of lipid phase transition temperatures and enthalpy changes. AB - The systematic study of the mesomorphic phase properties of synthetic and biologically derived lipids began some 30 years ago. In the past decade, interest in this area has grown enormously. As a result, there exists a wealth of information on lipid phase behavior, but unfortunately, these data have, until now, been scattered throughout the literature in a variety of books, proceedings, and journals. The data have recently been compiled in a centralized database with a view to providing ready access to the same and to the appropriate literature. The compilation facilitates review of what has thus far been accomplished and highlights what remains to be done in this active research area. As such, it represents a convenient summary of the existing data which, when evaluated, will enable us to identify where deficits exist in the data, to reveal the fundamental physicochemical principles upon which lipid phase behavior is based, and to understand more completely lipid phase relations in biological, reconstituted, and formulated systems. The compilation consists of a tabulation of all known mesomorphic and polymorphic phase transition temperatures and enthalpy changes for synthetic and biologically derived lipids in the dry and in the partially and fully hydrated states. Also included is the effect on these thermodynamic values of pH, and of salt and metal ion concentration and other additives such as proteins, drugs, etc. The methods used in making the measurements and the experimental conditions are reported. Bibliographic information includes complete literature referencing and list of authors. As of this writing, the database is current through June 1990 and contains 9500 records. Each record contains 28 fields. Here, we describe how the database originated, its scope and contents, data abstraction procedures, and issues relating to mesophase and lipid nomenclature, data analysis, and evaluation, and database maintenance and distribution. PMID- 1874824 TI - Clustering a large number of compounds. 2. Using the Connection Machine. AB - About 230,000 compounds in the National Cancer Institute Repository are available for screening under a new protocol. This paper is the second on an project to extract a representative sample of these compounds by clustering. The clustering program was implemented on the Connection Machine, a massively parallel computer with 16K processing elements. This implementation reduced a formidable task to a relatively routine run. PMID- 1874825 TI - Clustering a large number of compounds. 3. The limits of classification. AB - Clustering is normally used to group items that are similar. In this application of obtaining a diverse sample from the 230,000 compounds in the National Cancer Institute Repository, we cluster to select compounds that are different from the rest, to optimize screening for new leads. With these constraints, our approach yielded many singleton clusters. We can interpret these results as evidence for a limit to classification, contrary to the customary view of chemistry as a study of classes of compounds. PMID- 1874826 TI - Development of categorical identification of native and non-native bilabial stops: infants, children and adults. AB - Using an infant speech identification (ISI) procedure, English language environment infants, two- and six-year-old children, and adults were tested for their identification of sounds on a native (voiced/voiceless bilabial stop) and a non-native (prevoiced/voiced bilabial stop) speech continuum. Categorical perception of the two contrasts diverged as a function of age, increasing for the native contrast and decreasing for the non-native between two and six years. In Experiment 2, subjects of the same four ages were tested for their identification of a continuum of harmonic tones varying in pitch. Comparison of the results of Experiment 1 with the essentially continuous perception of this pitch continuum supports the view that the perception of the native contrast becomes more categorical with age, while perception of the non-native contrast becomes less categorical, especially at six years. Experiment 3, in which adults were tested on the three continua with a multi-trial open set procedure, demonstrated that results with the ISI procedure in Experiments 1 and 2 are comparable to results with more traditional methods. The results of the three experiments are discussed in terms of the role of specific linguistic experience in the development of categorical speech perception. PMID- 1874827 TI - Unusual phonological patterns and their underlying representations: a case study. AB - An unusual phonological pattern exhibited by a child aged 2;9 is described. The pattern involved the production of word-final strident continuants in words whose adult forms contain these features in initial, rather than final position (e.g. [ops] for soap). The data are interpreted as compatible with models of child phonology that permit direct mapping of features to final position. PMID- 1874828 TI - A longitudinal study of the relationship between early language development and play development. AB - Temporal correspondences between the attainment of specific milestones in play and language were examined through a longitudinal study of four Japanese children (aged 0;7 to 0;11 at the beginning of the study). There were developmental correspondences between the onset of six language landmarks (the emergence of first words, naming words, vocabulary spurts, word-chains, nonproductive two-word utterances, productive two-word utterances) and the onset of subcategories of play. Language and play both reflected the development of underlying symbolic ability, and both developed in parallel manner at the single-word stage. After the emergence of word-chains, language and play developed interdependently. All the children proceeded through the same sequence of stages, but the rate of development was different depending on their environment. PMID- 1874829 TI - Patterns of language learning-related behaviours: evidence for self-help in acquiring grammar. AB - Four kinds of language learning-related behaviours (LLRBs) were examined in the home conversations of six English children studied for six months from age 2;0 to 2;6. The speech of the children was coded for the number of times they participated in language lessons, language practice, metalanguage and revisions of prior language. All the children were active and frequent producers of LLRBs, with revisions being observed most commonly. Further analysis revealed that the majority of the revisions that the children initiated involved grammatical changes, with the revised utterances tending to be more grammatical than their predecessors. An auditory monitor is proposed as a partial explanation for revision behaviour, and is evaluated relative to other possible accounts of the findings. PMID- 1874830 TI - A little goes a long way: evidence for a perceptual basis of learning for the noun categories count and mass. AB - Various theories of learning for the categories count noun and mass noun are compared. It is argued that children assign words to these categories on the basis of intuitions arising from perception that are relevant to Macnamara's (1986) semantic definitions of the categories. These definitions rest on the centrality of identity in the meaning of nouns and the centrality of individuation in the meaning of count nouns but not mass nouns. Empirical evidence is presented that supports the hypothesis that young children classify words as count nouns or mass nouns on the basis of perceptual information about the extension of the words, that is, whether or not the extension consists exclusively of enduring individuals whose discreteness from one another is perceptually salient (count nouns) or not (mass nouns). In an experiment, 48 children with a mean age of 2;10 (S.D. = 0;5) were taught a word for a kind of object (i.e. a perceptually distinct individual) or for a kind of substance (i.e. a collection of small granules). For some children the word was syntactically count and for others it was syntactically mass. Half of the children received incongruous perceptual and syntactic cues. For most of these children, classification of the word was guided by the object- or substance-like appearance of the stimulus despite the presence of incongruent syntactic cues. Syntactic cues influenced classification of the word for a minority of subjects, most of whom were among the oldest in the sample. It is concluded that perceptual information is critical in early decisions about membership in the categories count noun and mass noun. PMID- 1874831 TI - When do children avoid backwards coreference? AB - This study investigated the claim that very young children avoid backwards coreference in their interpretation of sentences containing pronouns. Eighty-one children ranging in age from 3;1 to 8;0 and eight adults acted out four types of pronominal sentences. Cross-sectional data and individual response patterns reveal that children initially prefer internal coreference even when such a response is disallowed for structural reasons. Avoidance of backwards coreference appears to be a late developing phenomenon characteristic of six-year-olds. Adult response patterns, which are manifested by some very young children, emerge as the dominant pattern by age seven. PMID- 1874832 TI - Fuzzy boundaries and the extension of object-words. AB - An extensive fuzzy boundary was identified within the adult extension of two exemplary object-words, 'dog' and 'ball'. The fuzzy boundaries were incorporated into the standard of adult extension against which the preschool child's use of 'dog' and 'ball' was compared, and the investigation provided a framework in which children's responses to fuzzy boundary referents could be accommodated. Responses to fuzzy boundary referents were considered as having precedents within adult extension and the data revealed the provision of precedents for a significant number of the young child's applications and non-applications of the words. The investigation concluded that, through adherence to an oversimplified concept of adult extension, previous research has underestimated the degree of correspondence that exists between child and adult extension. PMID- 1874833 TI - Representational demands in mothers' talk to preschool children in two contexts: picture book reading and a modelling task. AB - Shared book reading is considered to be an influential factor in language and literacy development and has been associated with more complex and demanding forms of tutorial language use. The present study seeks to examine mothers' discourse in joint picture book reading in terms of the level of representational demand which it places on the child, that is the extent to which it requires the child to engage in abstract thought. This was compared with the language used in another interactive, but more product oriented task, modelling a clown using play doh. Twenty-four mother child dyads (in which the mean age of the children was 4;2) were videotaped while engaged on these tasks and the conversation was analysed for representational demand (levels of abstraction), interactive features and communicative function. The mother's conversation was found to be at a higher level of abstraction in reading than in play-doh modelling. The accuracy of child responses to high level requests for information was superior for reading, while responses to low level requests were similar in both situations. The interactive categories were more utterance-based and less attention-based than in the modelling task. PMID- 1874834 TI - A longitudinal analysis of young children's cohesion and noun specification in narratives. AB - The early production of nine cohesive devices during narration about personal experience was examined in an 18-month longitudinal study of 10 children between approximately age 2;0 and 3;6. The specification of noun phrases and types of noun errors were also explored. The number of cohesive ties increased with both age and MLU, due to increased pronominal reference and conjunctions (while clausal and verbal ellipsis decreased). Specific cohesive devices also were acquired at different MLU levels. Most noun phrases were non-problematic and errors declined with increasing age and MLU; specifically, noun omissions declined. However, when new nouns were introduced, approximately one out of five were ambiguous throughout the study. Thus, children's narratives become more comprehensible with age as cohesive links increase, and noun errors decrease, but at 3;6 children are still having difficulty properly managing the introduction of novel nouns. PMID- 1874835 TI - The development of noun definitions: a metalinguistic analysis. AB - Defining is a metalinguistic skill. This study charts the development of the ability to define. A total of 120 participants (40 at each of the ages of 10, 14 and 18 years) defined eight concrete and eight abstract nouns. Each definition was coded to identify the types of responses present in it. Results indicate that there are significant differences in the way concrete and abstract nouns are defined. All three age-groups defined concrete nouns mainly by class and characteristic responses. But it was not until age 18 that abstract nouns were defined by class and characteristic responses. The development of abstract noun definitions follows the development of concrete noun definitions. The ability to define is dependent upon knowledge of the meaning of the word but it is also dependent upon implicit or explicit knowledge of the definitional form. The ability to define abstract nouns is a late developing metalinguistic skill. PMID- 1874836 TI - Children's competence in the specialized register of sportscasting. AB - This study reports on four school-age boys' use of the specialized register of sportscasting as performed both spontaneously and when elicited by the researcher, and compares the boys' production of formal register-marking features to adult usage. Like the commentary of professional sportscasters, the boys' commentating is characterized by heavy use of simple-present action verbs, use of constructions lacking elements that are ordinarily grammatically required (the subject pronoun he, an auxiliary verb, or a main verb), and (in the elicited version) frequent occurrence of passives. The boys invest the most 'ungrammatical' utterance types (those lacking finite verbs) with a function that is not clearly present in adult sportscasting discourse, that of pointing forward in the discourse. PMID- 1874837 TI - Do children exploit the Maxim of Antecedent in order to interpret ambiguous descriptions? AB - Twenty Italian six-year-olds and 20 eight-year-olds were asked to interpret eight ambiguous and eight clear definite descriptions. All ambiguous descriptions could refer to three drawings, one of which had been described by the subjects immediately before the comprehension task. In half of the trials with ambiguous messages the children's interlocutor was present while the children were describing the drawings; in the other half he was absent. In both conditions subjects showed a preference for the referents they had already described, indicating that they applied egocentrically a comprehension strategy based on the Maxim of Antecedent (Jackson & Jacobs, 1982). Children's failures to differentiate their responses in the two conditions are considered to be due to difficulties in taking account of the given-new distinction for relevant information. PMID- 1874838 TI - The influence of linguistic context on young children's understanding of homophonic words. AB - This study investigates young children's understanding of homophones in two different linguistic contexts. Research has shown that children interpret homophones according to their 'primary' sense even though this is inappropriate to the linguistic context. The present study investigates the influence of different contexts on their interpretations of homophones. A picture test, similar to the British Picture Vocabulary Scale (BPVS), was devised, depicting ten homophones in both their primary and secondary senses. Forty-eight children who were in matched pairs following the BPVS pre-test and whose ages ranged from three to six were asked to select the picture which showed the homophone, first when the homophone was in no linguistic context, and secondly following one of two conditions of the same story which differed according to the richness of context provided. Results showed that those children assigned to story B, the expanded version with full linguistic details and explanations of the words it contained, were more able to identify correctly the secondary meanings of the homophones intended than those children given story A, the unexpanded version. Analyses of variance showed both a significant age trend and a story-type effect. These results are interpreted as showing that the linguistic context is an important factor in young children's understanding of word meaning. PMID- 1874839 TI - High-performance liquid chromatographic separation of bile acids and bile alcohols diastereoisomeric at C-25. AB - The high-performance liquid chromatographic separation of the 25R and 25S diastereoisomers of the bile alcohols 5 beta-cholestane-3 alpha,7 alpha,26-triol and 5 beta-cholestane-3 alpha,7 alpha, 12 alpha, 26-tetrol and the bile acids, 3 alpha,7 alpha-dihydroxy-5 beta-cholestane-26-oic acid and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestane-26-oic acid is described. A Radial-Pak microBondapak C18 reversed-phase cartridge was used for the separations and elutions were carried out with acetonitrile-water-methanol-acetic acid mixtures. All eight diastereoisomeric compounds showed baseline separation when up to 200 micrograms of the isomeric mixtures were injected into the column and the method can be used for isolation of pure diastereoisomers of these bile acids and bile alcohols. PMID- 1874840 TI - Use of polymeric reversed-phase columns for the characterization of polypeptides extracted from human pancreata. I. Effect of the mobile phase. AB - The high-performance liquid chromatographic (HPLC) behaviour of two different styrene-divinyl-benzene-based reversed-phase (RP) columns was evaluated using crude acetic acid extracts from normal and diabetic human pancreata as samples. Acetic acid gradients in water and acetonitrile gradients in triethylammonium phosphate (TEAP) and trifluoroacetic acid (TFA) were used as mobile phases, and comparisons were made with a silica-based C4 column. When two different polymeric RP columns were eluted with acetic acid gradients in water, surprisingly similar HPLC profiles of the pancreatic extracts were obtained. Elution of the polymer based columns with acetonitrile gradients in TFA or TEAP resulted in changes in the polypeptide selectivity of these columns, in parallel with that of a silica based C4 column eluted under similar conditions, indicating the general usability of polymeric columns for RP-HPLC of peptides and proteins. The pronounced difference in composition between normal and diabetic samples, which also was demonstrated after size-exclusion chromatography (SEC) on a silica-based and an agarose-based high-performance SEC column, was found to be related to the different ischaemia times for the two types of pancreata. PMID- 1874841 TI - Use of polymeric reversed-phase columns for the characterization of polypeptides extracted from human pancreata. II. Effect of the stationary phase. AB - The potential value of eight commercial available polymer-based reversed-phase (RP) columns for peptide and protein separations was evaluated using crude acetic acid extracts of normal and diabetic human pancreata and mixtures of pure polypeptides as samples. All columns were characterized with acetic acid gradients in water as mobile phase, and different chromatographic profiles were obtained depending on the type of polymer column (bare or derivatized) and the type of ligand. Some of the columns were virtually free from effects related to the polymer skeleton whereas in others the separation was influenced by both the ligand and the polymeric backbone. Two selected polymeric RP columns were, together with a silica-based C4 column, further characterized with acetonitrile gradients in trifluoroacetic acid (TFA), and the separation temperature was found to have a drastic effect on the separation efficiency for proteins with mol. wt. greater than 6000 dalton. No such effect was seen for polypeptides with mol. wt. less than 6000 dalton. Mixtures of pure peptides and proteins were separated using acetic acid gradients in water, acetonitrile or isopropanol, and normally the highest efficiency was found with the use of acetonitrile as mobile phase modifier. Isopropanol was less suitable as an organic modifier. The separation of the beta-lactoglobulin A- and B-chains may be used to give a rapid estimate of the chromatographic usability of polymer-based RP-columns for peptide and protein separations in acetic acid gradients in water and in acetonitrile gradients. Recoveries for insulin, proinsulin, growth hormone, ovalbumin and human serum albumin were measured for several polymer-based RP columns eluted with acetic acid gradients in water and with acetonitrile-based mobile phases. The highest recoveries of serum albumin and ovalbumin were found after elution with acetic acid gradients in water. PMID- 1874842 TI - Immunoaffinity chromatography, its applicability and limitations in multi-residue analysis of anabolizing and doping agents. AB - The use of (multi-)immunoaffinity chromatography in residue analysis is discussed. After an introduction to the immunochemical background an overview of applications is given. A distinction is made between the following methods: (1) single-antibody, single-analyte procedures; (2) single-antibody, multi-analyte procedures; (3) multi-antibody, multi-analyte procedures. It is concluded that immunoaffinity chromatography is superior to most other techniques for sample preparation and extract clean-up. Its advantages in multi-residue procedures are most clear when compared with e.g. high-performance liquid chromatography. In combination with gas chromatography-low-resolution mass spectrometry, very effective multi-residue methods are possible. Most frequently they concern screening procedures which can fulfill the identification criteria for reference methods. It is concluded that the use of (multi-)immunoaffinity chromatography will proliferate further in the 1990s. However, its future viability is highly dependent on the interest of commercial firms and on the involvement of the EC Community Bureau of Reference in manufacturing and supplying the necessary materials. PMID- 1874843 TI - Comparison of two mass-selective detectors with special reference to the analysis of residues of anabolics. AB - In the analysis of residues of anabolic agents the use of combined techniques, especially gas chromatography-mass spectrometry, is of increasing interest. When this method is used for the analysis of residues of anabolics it is very important to have a knowledge of the characteristics of the different types of apparatus on the market and to be sure that the results are not "apparatus dependent". In this study two mass-selective detectors, the Hewlett-Packard 5970 and the ion trap detector 800, were compared by injecting the same samples of derivatized anabolics (standard solutions) into the two systems. PMID- 1874844 TI - Detection of 19-nortestosterone and its urinary metabolites in miniature pigs by gas chromatography-mass spectrometry. AB - The metabolism of 19-nortestosterone was investigated in a miniature non castrated male pig (boar), in a castrated pig (barrow) and in a female pig (sow). Urine samples were taken before and at regular intervals after the injection of 100 mg of Laurabolin (nortestosterone laurate). The sample clean-up consists in preliminary solid-phase extraction, followed by high-performance liquid chromatographic purification and fractionation. Finally, gas chromatography-mass spectrometry is used to identify the 19-nortestosterone metabolites. PMID- 1874845 TI - Identification and characterization of 19-nortestosterone in urine of meat producing animals. AB - To monitor the illegal use of 19-nortestosterone as an anabolizing agent in meat production, the Belgian Institute of Veterinary Expertise applies a strategy of urine control by radioimmunoassay, positive samples being confirmed by thin-layer chromatography. We have evaluated this control strategy, using gas chromatography mass spectrometry to confirm the presence of 19-nortestosterone, or its metabolite oestrane-diol, in positive samples from radioimmunoassay. Our results show that the effective way of proceeding remains reliable in cattle, for mature and immature males as well as non-pregnant females, and in pigs, for pregnant and non-pregnant sows. The possible presence of endogenous 19-nortestosterone in cattle, in pregnant cows urine, and in pigs, in boars and in cryptorchid pigs, impedes the control of the use of 19-nortestosterone on these samples. False positive (not confirmed by gas chromatography-mass spectrometry) results were produced by radioimmunoassay in the urine of castrated pigs and sheep. PMID- 1874846 TI - Test strip enzyme immunoassays and the fast screening of nortestosterone and clenbuterol residues in urine samples at the parts per billion level. AB - The preliminary results of an investigation into the development of "on-site" test strip enzyme immunoassays for the screening of urine samples for the presence of growth promoters, such as 17 beta, 19-nortestosterone and clenbuterol at the parts per billion level are described. Urine samples, enzyme-labelled analyte and a nitrocellulose test strip, containing immobilized antibodies, are incubated together, after which the strip is placed in a chromogen-containing substrate solution for colour reaction. Using prefabricated strips, the tests can be performed in 45-60 min. A similar assay was worked out using a dot-blotting device, allowing the test to be performed in 20-50 min. The tests are simple and easy to perform outside the laboratory. Urine samples identified positive by gas chromatography mass spectrometry were also found to be positive with these test strips and, so far, no false-positive results have been encountered. With standard additions to blank urine samples, positive samples could be distinguished above the 5 ng ml level. However, samples from treated calves contain one or more metabolites of the parent compound, which increase the sensitivity of the assays. Although the tests described can be improved and still have to be evaluated further by analysing more urine samples, the preliminary results are very promising and give a lead to further research into the applicability of such "on-site" tests in residue analysis. PMID- 1874847 TI - Control system for detection of the illegal use of naturally occurring steroids in calves. AB - Within the scope of the National Plan for Hormone Control in The Netherlands, a study was performed to develop a system for control of the illegal use of three naturally occurring hormones [oestradiol-17 beta (E2-17 beta), testosterone (T), progesterone (P)] for fattening purposes in animal production. Using a specific high-performance liquid chromatographic-radioimmunoassay method, reference values were established for concentrations of E2-17 beta, T and P and some of their metabolites in blood plasma and urine from untreated male and female veal calves. E2-17 beta levels of both male and female calves were less than 0.01 microgram/l in blood plasma and less than 0.2 microgram/l in urine. For male veal calves levels of T and epitestosterone (epiT) in blood plasma and urine varied widely. The P levels were less than 0.1-0.3 micrograms/l in blood plasma and less than 0.6-10 micrograms/l in urine from both male and female calves. To investigate the effect of anabolic treatment on the hormone levels in plasma and excreta, male veal calves were injected, subcutaneously into the dewlap, with a solution containing 20 mg of E2-17 beta benzoate and 200 mg of T propionate in 5 ml of arachis oil. Only the levels of E2-17 beta and E2-17 alpha in blood plasma and excreta were elevated until about one week after injection, compared with the untreated control calves and the reference values. T and epiT levels were similar in plasma and excreta from both untreated and treated animals. PMID- 1874848 TI - Combined high-performance liquid chromatography and radioimmunoassay for the screening of 19-nortestosterone and methyltestosterone residues in meat samples. AB - A procedure is described for the detection of 17 beta-19-nortestosterone (17 beta 19-NT) and 17 alpha-methyltestosterone (17 alpha-MT) in muscle tissue by a combination of high-performance liquid chromatography and radioimmunoassay. The steroids were released from the muscle tissue by enzyme digestion, and the extracts were purified by solid-phase extraction. A meat sample from the retail trade, which was proved to contain 17 beta-19-NT and 17 alpha-MT residues by gas chromatography-mass spectrometry, and blank meat samples obtained from non treated experimental animals were purified and the extracts injected into the liquid chromatograph. With an automatic fraction collector, fifteen fractions of 1 ml each were obtained, which after evaporation were subjected to a radioimmunoassay for the steroid concerned. It was demonstrated that none of the fractions from the blank meat samples contains any substance that interfered with the immunochemical detection system. In addition, a good qualitative agreement between the two sets of results was obtained. Although the sample preparation step is rather labour-intensive, the method can be successfully applied as a reliable confirmation method for positive radioimmunoassay screening results in circumstances where no gas chromatography-mass spectrometry facilities are available. PMID- 1874849 TI - Development of a competitive enzyme immunoassay for 17 alpha-19-nortestosterone. AB - Because 17 beta-19-nortestosterone and its esters are frequently used anabolic steroids in cattle in Europe, there is a need for an assay that can also detect certain metabolites. The enzyme immunoassay described here involves the detection and quantitation of the major metabolite 17 alpha-19-nortestosterone in urine. The assay is based on the coating of an antibody raised in a rabbit against 17 alpha-19-nortestosterone-3-carboxy-methyloxime-bovine serum albumin (17 alpha-19 NT-3-CMO-BSA), the competitive incubation of 17 alpha-19-NT and the 17 alpha-19 nortestosterone-3-CMO-horseradish peroxidase label, followed by the detection of the blue colour developed by the action of the enzyme on tetramethylbenzidine. The 3-CMO conjugate of 17 alpha-19-nortestosterone was used to produce an antibody with selective affinity for the 17 alpha-epimer. For the optimization of the assay, different coatings and incubation conditions were tested. The standard curve ranged between 0.98 and 4000 pg per well, with a B/B0 50% of +/- 65 pg per well. Colour was measured with a microtitre plate reader. The method was validated by means of certified blank and spiked cattle urine samples. PMID- 1874850 TI - Use of an immobilized enzyme reactor for the analysis of residues of 17 alpha methyltestosterone in trout by high-performance liquid chromatography. AB - We have recently observed in trout that 48 h after ingestion of a single dose of [14C]-17 alpha-methyltestosterone ([14C]-MT), 25% of the radioactivity was still in the carcass, corresponding to metabolites of 17-MT. These compounds have no appreciable chromophore, fluorophore or electrophore, therefore the usual detection systems was not satisfactory for their analysis. Consequently a method was developed for high-performance liquid chromatographic separation and detection of two of the major tissue metabolites of 17-MT: 5 alpha-androstane-17 alpha-methyl-3 alpha,17 beta-diol and 5 beta-androstane-17 alpha-methyl-3 alpha,17 beta-diol. A column of immobilized 3 alpha-hydroxysteroid dehydrogenase was prepared and used for detection. The NADH produced from 3-hydroxysteroids by this immobilized enzyme reactor was monitored fluorimetrically. The detection limit of this method, as obtained from the calibration curve, was at the picomole level; the limit of quantification in muscle was 1 microgram/kg, at a signal-to noise ratio of 4. PMID- 1874851 TI - Detection of the illegal use of ethinylestradiol in cattle urine by gas chromatography-mass spectrometry. AB - A method for the detection of ethinylestradiol in cattle urine is described, based on enzymic hydrolysis of the sample, clean-up by means of disposable octadecyl and amino solid-phase extraction columns, fractionation by reversed phase high-performance liquid chromatography, and detection by gas chromatography mass spectrometry (selected-ion monitoring). Identification is based on both gas chromatographic and mass spectrometric data. The method has been tested on urine samples for a collaborative study and all the results found were correct. PMID- 1874852 TI - Rapid screening method for the determination of diethylstilbestrol in edible animal tissue by column liquid chromatography with electrochemical detection. AB - A rapid and sensitive screening method for the determination of residues of diethylstilbestrol in edible animal tissue is described. The analyte was extracted from the tissue with tert.-butyl methyl ether, reextracted with 1 M sodium hydroxide and further cleaned up by solid-phase extraction with C18 cartridges. Analysis was performed by isocratic elution with a phosphate-buffered mobile phase, methanol-0.05 M phosphate buffer pH 3.5 (67:33), on a Nucleosil 5 microns C18 column with electrochemical detection at +0.90 V. The average recovery of trans-diethylstilbestrol in spiked samples is 66%, with a standard deviation of 14% (n = 22) in the range 0.5-2.0 microgram/kg. The detection limit is 0.1-0.2 microgram/kg, although at this level other compounds may interfere and give rise to false positive results. PMID- 1874853 TI - Disposition of 17 beta-trenbolone in humans. AB - The urinary excretion and metabolic pattern of 17 beta-trenbolone, a synthetic anabolic steroid hormone used as a growth promotor for beef cattle in several countries, has been studied in a human subject. For the separation of the metabolites of 17 beta-trenbolone, a reversed-phase high-performance liquid chromatographic method was established. The method was tested with metabolites obtained from incubation of 17 beta-trenbolone with rat liver microsomes. Fifteen metabolites could be well separated in one run by using a concave acetonitrile water-methanol gradient. After ingestion of the tracer-labelled hormone at a dose of 0.04 mg/kg body weight 54% of the administered radioactivity was found in the urine after 26 h and 63% after 72 h. Of the urinary material 54% was present as glucuronides, which contained mostly 17 alpha-trenbolone, 17 beta-trenbolone and trendione. At least five other polar metabolites, presumably hydroxylated products, were found in smaller amounts, mostly in the unconjugated and sulphated fractions. Thus, the disposition of 17 beta-trenbolone in humans differs significantly from that in rats, which may have a bearing on the toxicological evaluation of the hormone. PMID- 1874854 TI - Determination of zeranol and beta-zearalanol in calf urine by immunoaffinity extraction and gas chromatography-mass spectrometry after repeated administration of zeranol. AB - A method for the determination of zeranol and its metabolite beta-zearalanol in bovine urine is described. It has been applied to samples from calves given multiple subcutaneous doses of zeranol. Samples were extracted with immunoaffinity columns containing antibodies raised against zeranol and were analysed by gas chromatography-mass spectrometry. The immunoaffinity columns were prepared by coupling immunoglobulin G fractions obtained from rabbit antisera with a Sepharose matrix. The immunizing agent was carboxybutylzeranol coupled to bovine serum albumin. Gas chromatography-mass spectrometry was performed in the negative-ion chemical ionization mode, after derivatization of the compounds to their pentafluorobenzyl ethers, and allowed detection of analytes with a sensitivity of 0.01 ppb in spiked urine. The derivatization method and the gas chromatographic determination were also applied to the similar compounds zearalanone, zearalenone and beta-zearalenol. A synthesis of dideuterated zeranol and beta-zearalanol by isotopic exchange is described. These deuterated analogues had an isotopic purity of more than 99% and were used for quantitation of zeranol and beta-zearalanol by isotope dilution mass spectrometry. The recoveries of zeranol and beta-zearalanol, using the immunoaffinity columns, were determined after extraction from spiked urine and were 84 and 64%, respectively. The urines of treated calves were collected for several days after treatments and were analysed after hydrolysis with beta-glucuronidase and arylsulphatase. The samples showed variable but generally decreasing concentrations of zeranol and beta zearalanol. The levels of beta-zearalanol ranged from less than 0.01 to 98 ppb and were 1.2-3.2 times higher than those of zeranol. PMID- 1874855 TI - Screening and confirmatory analysis of beta-agonists, beta-antagonists and their metabolites in horse urine by capillary gas chromatography-mass spectrometry. AB - A method for the screening and confirmatory analysis of beta-agonists and antagonists in equine urine is described. Following initial enzymic hydrolysis, the basic drugs and metabolites are extracted using Clean Screen DAU or Bond Elut Certify cartridges, and analysed as their trimethylsilyl ether or 2-(dimethyl) silamorpholine derivatives by capillary gas chromatography-mass spectrometry. The method proved to be very sensitive and selective for basic drugs. After administration of therapeutic doses of propranolol, metoprolol, timolol, isoxsuprine and clenbuterol to thoroughbred horses, the parent compound/metabolites could be detected in urine for upto 14-120 h depending on the drug. PMID- 1874856 TI - Determination of clenbuterol in urine as its cyclic boronate derivative by gas chromatography-mass spectrometry. AB - A rapid and reliable gas chromatographic-mass spectrometric method for the determination of clenbuterol in urine is described. Penbutolol was used as internal standard. Four derivatization procedures have been tested, of which 1 butaneboronic acid gave the best results. The method includes extraction of the alkalinized urine (3 ml) with tert.-butyl methyl ether-n-butanol (9:1), derivatization with 1-butaneboronic acid (15 min at room temperature), and analysis in the selected-ion monitoring mode of the derivatives of clenbuterol at m/z 243, 327 and 342 and of penbutolol at m/z 342 and 357. The detection limit is 0.5 ng/ml and the recovery better than 90%. PMID- 1874857 TI - High-performance liquid chromatography with electrochemical detection of buprenorphine and its major metabolite in urine. AB - A procedure was developed for the simultaneous determination of buprenorphine and its major metabolite. N-desalkylbuprenorphine, by reversed-phase high-performance liquid chromatography with electrochemical detection. The detection limit is about 100 pg/ml for the major metabolite and 250 pg/ml for buprenorphine. PMID- 1874858 TI - Rapid high-performance liquid chromatographic determination with fluorescence detection of furosemide in human body fluids and its confirmation by gas chromatography-mass spectrometry. AB - Furosemide (FD: Lasix) is a loop diuretic which strongly increases both urine flow and electrolyte urinary excretion. Healthy volunteers were administered 40 mg orally (dissolved in water) and concentrations of FD were determined in serum and urine for up to 6 h for eight subjects, who absorbed water at a rate of 400 ml/h. Quantification was performed by HPLC with fluorescence detection (excitation at 233 nm, emission at 389 nm) with a limit of detection of 5 ng/ml for a 300-microliters sample. The elution of FD was completed within 4 min using a gradient of acetonitrile concentration rising from 30 to 50% in 0.08 M phosphoric acid. The delay to the peak serum concentration ranged from 60 to 120 min. FD was still easily measurable in the sera from all subjects 6 h after administration. In urine, the excretion rates reached their maximum between 1 and 3 h. The total amount of FD excreted in the urine averaged 11.2 mg (range 7.6 14.0 mg), with a mean urine volume of 3024 ml (range 2620-3596 ml). Moreover, the urine density was lower than 1.010 (recommended as an upper limit in doping analysis to screen diuretics) only for 2 h. An additional volunteer was administered 40 mg of FD and his urine was collected over a longer period. FD was still detectable 48 h after intake. Gas chromatography-mass spectrometry with different types of ionization was used to confirm the occurrence of FD after permethylation of the extract. Negative-ion chemical ionization, with ammonia as reactant gas, was found to be the most sensitive method of detection. PMID- 1874859 TI - Separation of cholesterol esters by silver ion chromatography using high performance liquid chromatography or solid-phase extraction columns packed with a bonded sulphonic acid phase. AB - Two methods for the separation of cholesterol esters, based on the number of double bonds in their fatty acid moieties, are presented. Silver ion chromatography, usually performed on thin-layer chromatographic plates, was made suitable for high-performance liquid chromatography (HPLC) and solid-phase extraction. Separation on a bonded sulphonic acid phase loaded with silver ions was achieved with cholesterol esters containing up to six double bonds in their fatty acid moieties. No cross-contamination between fractions with different numbers of double bonds was detected with the HPLC method, was demonstrated by subsequent gas chromatographic analysis of the fatty acid moieties, following transmethylation. For adequate separations with the solid-phase extraction columns it proved important to avoid overloading. The methods may be of use for the off-line analyses of the sterol compositions of the isolated fractions, which each contain sterol esters with an equal number of double bonds in their fatty acid moieties. PMID- 1874860 TI - High-performance liquid chromatographic separation of bile acid pyrenacyl esters with cyclodextrin-containing mobile phase. AB - The high-performance liquid chromatographic separation of bile acid pyrenacyl esters with cyclodextrin-containing mobile phase is presented. Compared with conventional methods, inclusion chromatography gives much more satisfactory separation of derivatized bile acids in a short time. The application of this method to the separation of glycine-conjugated bile acids in human bile is also described. PMID- 1874861 TI - Fatty acid composition of glycerophospholipids in seven tissues of cod (Gadus morhua), determined by combined high-performance liquid chromatography and gas chromatography. AB - A method for the separation from fish tissues of the four main glycerophospholipid classes, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine, using adsorption high-performance liquid chromatography with ultraviolet detection and consecutive gas chromatographic analysis, based on one injection for their fatty acid compositions, is described. Fatty acid 19:0 was used as an internal standard for the calculation of the relative concentrations of the phospholipids. The patterns of fatty acid distribution within each of the phospholipids from seven cod organs had some general similarities. Phosphatidylcholine had the highest levels of 16:0 and 18:2 n - 6, and the ratio of 20:5 to 22:6 varied between 0.5 and 0.9. Phosphatidylethanolamine had the highest total polyunsaturated fatty acids, (n 3) polyunsaturated fatty acids, and 22:6 n -3, and the ratio of 20:5 to 22:6 varied between 0.2 and 0.5. Phosphatidylinositol showed the highest level of 18:0 and 20:4 n - 6 and had the lowest ratio of (n - 3) to (n - 6). Phosphatidylserine had the highest ratio of (n - 3) to (n - 6) and the lowest ratio of 20:5 to 22:6. A generally low level (less than 1.5%) of the long-chain monoene, 22:1, was found in the phospholipids in all tissues. PMID- 1874862 TI - Improved high-performance liquid chromatographic method for the routine determination of unconjugated 3-methoxy-4-hydroxyphenylethyleneglycol in human plasma using solid-phase extraction and electrochemical detection. AB - An improved semi-automated high-performance liquid chromatographic method is described for the routine determination of unconjugated 3-methoxy-4 hydroxyphenylethyleneglycol in plasma. The 3-ethoxy analogue of the compound is used as an internal standard. The method is based on purification of 0.5-ml plasma samples with phenyl-type reversed-phase extraction columns, reversed-phase separation with an acetate-citrate-methanol mobile phase with an octadecyl-bonded column, and dual-electrode coulometric detection with oxidation at +0.44 V and reduction at -0.25 V. The precision and accuracy of the assay are satisfactory: the lower limit of reliable detection corresponds to a plasma concentration of 1.5 nM. The validity of the determination is demonstrated by an 18% mean increase in plasma levels of 3-methoxy-4-hydroxyphenylethyleneglycol during physical exercise (duration 16 min, n = 13) and a 50% mean reduction in plasma levels induced by a single dose of the monoamine oxidase inhibitor, moclobemide (n = 8). The method is suitable for routine use in pharmacological and physiological experiments. PMID- 1874863 TI - Measurement of reduced and oxidized glutathione in cultures of adult rat hepatocytes. AB - A reversed-phase ion-exchange high-performance liquid chromatographic technique, suitable for the separate measurement of reduced (GSH) and oxidized (GSSG) glutathione in cultures of adult rat hepatocytes, is described. A commercially available Nucleosil 120-7NH2 column was used. A complete run took ca. 22 min. The retention times for GSH and GSSG were 10.6 and 12.7 min, respectively, providing a resolution coefficient of 1.4. The coefficients of variation for GSH and GSSG were ca. 5 and 25%, respectively, for freshly isolated hepatocytes, and 16 and 15%, respectively, for 24-h cultured hepatocytes. The detector response was linear as a function of GSH and GSSG concentration and the hepatocytes concentration studied. Addition of up to 1.5 mg/ml bovine serum albumin to the culture medium had no effect on the linearity. The recovery for standards, ranging from 0 to 150 nmol of GSH or GSSG per millilitre in the presence of hepatocytes, was 98% for GSH and 80% for GSSG. The detection limit of the method was between 0.5 and 1.0 nmol of GSH and GSSG per millilitre. In cultured rat hepatocytes, the GSH content increased during the first 24 h of culture, followed by a slow decrease. After six days of culture, the GSH content was less than 50% of the value found for freshly isolated hepatocytes. GSSG was present in cultured rat hepatocytes in only small amounts and becomes unmeasurable after four days of culture. PMID- 1874864 TI - Solid-phase extraction of plasma vasopressin: evaluation, validation and application. AB - A new solid-phase extraction method using octyl-silica columns to extract vasopressin-like immunoreactivity from plasma has been developed. The extraction was followed by a radioimmunoassay on the vacuum-dried extracts, which were reconstituted in assay buffer. The total recovery of synthetic vasopressin was ca. 100%. Based on co-elution with synthetic vasopressin after separation by reversed-phase high-performance liquid chromatography of plasma extracts from normal Wistar and Brattleboro rats, and the cross-reactivity of the antiserum used in the radioimmunoassay system, the extracted material was found to be indistinguishable from authentic vasopressin. Unknown experimental samples were interpolated on a standard curve established in "zero" plasma (plasma derived from rats subjected to waterload) spiked with known amounts of synthetic vasopressin, and not on a standard curve established in assay buffer. The limit of detection was 1 fmol of vasopressin equivalent per millilitre. The intra- and inter-assay coefficients of variance were 10-16% and 16%, respectively. The procedure reliably showed that osmotic challenge and 24-h dehydration increased, whereas ethanol ingestion decreased vasopressin-like immunoreactivity plasma levels in the rat, compared with normally hydrated controls. PMID- 1874865 TI - Determination of proteins in urine by high-performance liquid chromatography with spectrophotometric detection using a pyrogallol red-molybdate complex. AB - A high-performance liquid chromatographic method with spectrophotometric detection was developed for the determination of proteins in urine. The proteins were separated on an anion-exchange column and eluted with a Tris-HCl buffer with a gradient of sodium chloride concentration and pH. The separated proteins were mixed with a pyrogallol red-molybdate complex reagent and determined spectrophotometrically. Urinary proteins were well separated without desalting the urine. The reproducibility was satisfactory. PMID- 1874866 TI - Immobilized urokinase column as part of a specific detection system for plasminogen species separated by high-performance affinity chromatography. AB - Immobilized urokinase was used as part of a post-column reactor for the specific detection of human plasminogen species which were fractionated using a high performance affinity column. After on-line activation of each peak, plasmin activity was measured by mixing the eluate with a specific fluorogenic substrate and the product was detected by a fluorescence monitor. This detection system gave linear calibration graphs for both purified plasminogens (0.1-50 micrograms) and plasminogens contained in plasma (25-100 microliters). Relative standard deviations for the determination of plasminogens in plasma were 6.1-6.6% (n = 12), showing good reproducibility. The detection limit was as low as 0.1 micrograms of plasminogen. Immobilized urokinase was very stable and no appreciable decrease in activity was found after 100 cycles of operation. In combination with an immobilized benzamidine column, this system made it possible to separate and detect Glu-plasminogen and Lys-plasminogen contained in human plasma samples as small as 100 microliters without any pretreatment. PMID- 1874867 TI - Micellar electrokinetic capillary chromatographic separation and laser-induced fluorescence detection of 2'-deoxynucleoside 5'-monophosphates of normal and modified bases. AB - Micellar electrokinetic chromatography is used to separate dansylated nucleotides, both normal and modified species. The high separation power allows detection of minor components present in less than 1 part per thousand of the major components. Laser-excited fluorescence is used to detect the separated components at the 6 x 10(-18) mol level or 10(-9) M injected material. Combined with high-performance liquid chromatographic enrichment prior to labeling, this technique can be used to assess DNA damage in carcinogenesis studies. PMID- 1874868 TI - Automated screening procedure using gas chromatography-mass spectrometry for identification of drugs after their extraction from biological samples. AB - A novel analytical screening procedure has been developed, using computer controlled gas chromatography-mass spectrometry (GC-MS), to detect 120 drugs of interest to road safety. This paper describes GC-MS methodology suitable for use on extracts of biological origin, while extraction procedures will be the subject of a future communication. The method was devised to identify drugs in extracts of blood samples, as part of an investigation into the involvement of drugs, other than alcohol, in road accidents. The method could be adapted to screen for other substances. The method depends on a "macro" program which was written to automate the search of GC-MS data for target drugs. The strategy used was to initially search for each drug in the database by monitoring for a single characteristic ion at the expected retention time. If a peak is found in this first mass chromatogram, a peak for a second characteristic ion is sought within 0.02 min of the first and, if found, the ratio of peak areas calculated. Probable drug identification is based on the simultaneous appearance of peaks for both characteristic ions at the expected retention time and in the correct ratio. If the ratio is outside acceptable limits, a suspected drug (requiring further investigation) is reported. The search macro can use either full mass spectra or, for enhanced sensitivity, data from selected ion monitoring (which requires switching between groups of ions during data acquisition). Quantitative data can be obtained in the usual way by the addition of internal standards. PMID- 1874869 TI - Determination of ritodrine in biological fluids of the pregnant sheep by fused silica capillary gas chromatography using electron-capture detection. AB - A sensitive and selective gas chromatographic assay method employing splitless injection, fused-silica capillary columns and electron-capture detection is reported for the quantitation of the tocolytic drug, ritodrine, in a variety of biological fluids obtained from the pregnant ewe and fetus. This method has improved sensitivity and selectivity over previously published assay procedures. A 25 m x 0.31 mm I.D., cross-linked 5% phenylmethylsilicone, fused-silica capillary column was employed for all analyses. Linearity of response was observed over the range 2.5-75 ng of ritodrine base per 0.05-0.5 ml of biological fluid, representing approximately 1-75 pg at the detector. The coefficient of variation was less than 10% over the range 2.5-75 ng of added ritodrine. The minimum quantifiable amount is approximately 2.5 ng from a 0.5-ml biological fluid sample. Applicability of this method to biological fluids, obtained from ovine subjects, is demonstrated by the analysis of samples obtained during the course of ritodrine placental transfer studies. PMID- 1874870 TI - Determination of felodipine and its metabolites in plasma using capillary gas chromatography with electron-capture detection and their identification by gas chromatography-mass spectrometry. AB - A novel method for the determination of felodipine and its metabolites in plasma by capillary gas chromatography (GC) with electron capture detection was developed. Felodipine and its oxidized metabolite were assayed by capillary GC after solid-phase extraction with the aid of a cool on-column injection technique. Acid metabolites, methyl monoacid and ethyl monoacid and diacid, were extracted with diethyl ether and propylated with 1-n-propyl-3-p-tolyltriazene before being submitted to capillary GC. These methods were very sensitive and useful for the pharmacokinetic study of felodipine. Felodipine and its metabolites were identified by GC-mass spectrometry. The mass spectral patterns of the peaks of extracts from human plasma samples after oral administration of felodipine were in good agreement with those of reference compounds. PMID- 1874871 TI - Determination of pethidine and its major metabolites in human urine by gas chromatography. AB - Procedures based on gas chromatography were established to determine pethidine and its major metabolites in human urine. The chromatographic system consisted of a glass column packed with 3% (w/w) SP2250 on Chromosorb W (80-100 mesh) linked to a nitrogen-phosphorus detector. Diethyl ether was used as the extraction solvent. Pethidinic and norpethidinic acids, and their conjugated metabolites (after beta-glucuronidase treatment) were determined after conversion into pethidine and norpethidine by acid-catalysed esterification. The retention times of pethidine, norpethidine and chlorpheniramine (internal standard) were 3.3, 4.5 and 7.5 min, respectively. The amount of unchanged drugs and metabolites excreted varied considerably among the subjects. The mean 24-h urinary recoveries in eight patients of pethidine, norpethidine, pethidinic acid, norpethidinic acid, and the glucuronides of pethidinic and norpethidinic acids were 6.62 +/- 5.05, 4.33 +/- 1.19, 18.9 +/- 6.29, 9.10 +/- 4.26, 15.1 +/- 3.02 and 7.57 +/- 2.28%, respectively. This indicates that the major metyabolic pathways of pethidine in the eight patients were hydrolysis followed by conjugation. Over 60% of the dose was accounted for in 24 h after intramuscular administration of 1 mg/kg pethidine. PMID- 1874872 TI - Bioanalysis of erythromycin 2'-ethylsuccinate in plasma using phase-system switching continuous-flow fast atom bombardment liquid chromatography-mass spectrometry. AB - A specific method for the determination of erythromycin 2'-ethylsuccinate (EM-ES) in plasma is described. The method involves a liquid-liquid extraction procedure followed by the analysis of extracts using phase-system switching (PSS) continuous-flow fast atom bombardment (CF-FAB) liquid chromatography-mass spectrometry (LC-MS). In PSS EM-ES is enriched after analytical separation on a short trapping column, from which it is desorbed to the LC-MS interface. In this way, favourable mobile phases can be used for the LC separation and for the MS detection. Using the PSS approach a flow-rate reduction from 1.0 ml/min in the LC system to 15 microliters/min going into the mass spectrometer was achieved without splitting. The determination limit for EM-ES was 0.1 microgram/ml. PMID- 1874873 TI - Identification by gas chromatography and mass spectrometry of lipids from the rat Harderian gland. AB - Lipids from rat Harderian glands were extracted with ethyl acetate, hydrolysed with base and examined by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) as trimethylsilyl (TMS), [2H9]TMS, methyl ester-TMS, picolinyl, nicotinate and nicotinylidene derivatives. The latter three derivatives were used to reveal the structures of the alkyl chains of fatty acids, alcohols and glycerol ethers, respectively. Forty-eight compounds were identified, representing about 97% of the total extracted lipids as measured by GC peak areas. The major constituents were fatty acids with chain lengths from 12 to 22 carbon atoms (mainly C18 and C20) and fatty alcohols (C16 to C26) derived from wax esters. Most of these acids and alcohols were unsaturated in the omega-7 position and were accompanied by smaller amounts of the saturated and omega-5 monounsaturated analogues. glycerol ethers were also identified for the first time in this secretion; the ether chains contained from 14 to 19 carbon atoms (mainly 16) and were straight-chain saturated, unsaturated (omega-5 and omega-7) and branched (iso). The only sterol found was cholesterol amounting to 1.24% of the total extract. PMID- 1874874 TI - High-performance liquid chromatographic determination of PEG 600 in human urine. AB - Polyethylene glycols (PEGs) are non-ionic, water-soluble synthetic polymers which have been widely used for many applications. Since they are of very low toxicity and are readily excreted in urine, PEGs in the molecular weight range 400-6000 have been used extensively in the study of intestinal physiology in man. A high performance liquid chromatographic (HPLC) method has been developed for the determination of PEG 600 in human urine, which includes a pre-column derivatisation step. The dibenzoate derivatives of PEG 600 can be quantitatively prepared, and this, coupled with ultraviolet detection at 230 nm, has greatly improved the limit of detection for the determination of PEGs by HPLC. A suitable extraction procedure has also been developed which enabled PEG levels in urine to be monitored with much greater sensitivity than any previously reported method. PMID- 1874875 TI - Novel direct high-performance liquid chromatographic method for determination of salicylate glucuronide conjugates in human urine. AB - A novel direct high-performance liquid chromatographic (HPLC) assay for the simultaneous determination of three salicylate glucuronide conjugates and other salicylate metabolites in human urine has been developed. Salicylate glucuronide conjugates were purified by HPLC from the urine of a volunteer after oral administration of aspirin and identified by selective hydrolysis with beta glucuronidase and with sodium hydroxide. This method gave high reproducibility with coefficients of variation less than 10%. The total urinary recovery of salicylic acid after a single 1.2-g dose of soluble aspirin was greater than 90%. This assay has been successfully used to re-evaluate the capacity-limited pharmacokinetics of salicylic acid in humans. PMID- 1874876 TI - High-performance liquid chromatographic determination of the 1,4-diketo and 1,4 diketo-2,3-dihydroxy metabolites of lonapalene in rat urine. AB - Individual high-performance liquid chromatographic (HPLC) methods have been developed for the determination of two major metabolites of lonapalene in rat urine. The highly unstable and polar 1,4-diketo-2,3-dihydroxy metabolite (II) is extracted from urine by two extraction columns (phenyl followed by silica), further purified by means of HPLC with a fully end-capped C18 HPLC column and quantified by an ultraviolet detector at 280 nm. Ascorbic acid is used as an antioxidant during extraction and overnight injection of II. Urine samples for total II (free plus conjugated) determination are incubated with arylsulfatase and beta-glucuronadase prior to extraction. The 1,4-diketo metabolite (III) is extracted from urine with a C18 extraction column, further purified with a C18 HPLC column, and quantified by an ultraviolet detector at 260 nm. The detection limit for both metabolites is 100 ng/ml of urine (signal-to-noise = 2.5). The methods were used to analyze urine samples from a long-term toxicology study of lonapalene in rats and to determine the linearity of dose-concentration relationships for both metabolites. PMID- 1874877 TI - High-performance liquid chromatography method for serum methotrexate levels in children with severe steroid-dependent asthma. AB - Monitoring of low-dose methotrexate (MTX), as used in severe steroid-dependent asthma, requires a sensitive and reproducible technique which has hitherto not been available. A high-performance liquid chromatographic method for the determination of MTX in serum is reported. The method involves deproteinization with acetone followed by addition of butanol and diethyl ether. The percentage recovery with this method compared with others was high (90 versus 70%). The samples were chromatographed on a reversed-phase ODS column and monitored at 313 nm. The retention time for MTX was 14.7 min. Pharmacokinetics of MTX was studied in five patients (age 3-15 years) with severe asthma who received a weekly oral dose of 10 mg/m2 body surface area. Following administration, the serum disappearance was monophasic with a half-life of 5 h. A metabolite, 7 hydroxymethotrexate was detected in serum after 2 h and reached a maximum concentration after 6 h. This new method will facilitate monitoring of asthmatic patients on methotrexate and allow for dose response and toxicity studies to be conducted. PMID- 1874878 TI - Simultaneous determination of testosterone and androstadienone (sex attractant) in human plasma by gas chromatography-mass spectrometry with high-resolution selected-ion monitoring. AB - Androsta-4,16-dien-3-one (androstadienone) and androst-4-en-3-one-17 beta-ol (testosterone) in healthy human plasma were simultaneously determined under several experimental conditions by gas chromatography-mass spectrometry with high resolution selected-ion monitoring. Internal standards were [2,2,4,6,6 2H5]androstadienone and [2,2,4,6,6-2H5]testosterone. Samples were extracted with an Extrelut column, purified using Lipidex 5000 and converted into hydroxime trimethylsilyl derivatives for determination. Physiological concentrations of androstadienone and testosterone found in eleven healthy men were 2.05 +/- 0.74 and 18.6 +/- 4.9 pmol/ml in plasma (mean +/- S.D.), respectively. No correlation was observed between these steroid concentrations. PMID- 1874879 TI - Simple and rapid micro-analytical procedures for the estimation of milacemide and its metabolite glycinamide in rat plasma and cerebrospinal fluid by high performance liquid chromatography. AB - A high-performance liquid chromatographic technique is described for the determination of milacemide and its primary metabolite glycinamide in rat plasma and cerebrospinal fluid. Milacemide and glycinamide are derivatized with fluorescamine to form a chromophore and a fluorophore and subsequent analysis using ultraviolet and fluorescence detectors, respectively. The extraction procedures are simple with a limit of detection 2 and 0.5 micrograms/ml for milacemide in plasma and cerebrospinal fluid, respectively, and 0.5 micrograms/ml for glycinamide in plasma or cerebrospinal fluid. The within-batch coefficients of variation for both analytes were less than 3%. Since only a small amount of sample is required, these techniques are well suited for the study of milacemide pharmacokinetics in the rat. PMID- 1874880 TI - Determination of benperidol and its reduced metabolite in human plasma by high performance liquid chromatography and electrochemical detection. AB - An isocratic high-performance liquid chromatographic method with electrochemical detection for the quantification of benperidol and its suggested reduced metabolite TVX Q 5402 in human plasma is described. The method included a two step solid-phase extraction on reversed-phase and cation-exchange material, followed by separation on a cyanopropyl silica gel column (5 microns; 250 mm x 4.6 mm I.D.). The eluent was 0.15 M acetate buffer (pH 4.7) containing 25% acetonitrile (w/w). Spiperone served as internal standard. The inclusion of the cation-exchange step provided sample purity higher than those achieved with other methods. After extraction of 1 ml of plasma, concentrations as low as 0.5 ng/ml were detectable for both benperidol and the metabolite. In plasma samples collected from a schizophrenic patient treated with a single oral dose of 6 mg of benperidol, plasma levels of benperidol and of the metabolite could be measured from 20 min to at least 12 h after administration. PMID- 1874881 TI - Determination of the retinoid (E)-1,2,3,4-tetrahydro-1,1,4,4-tetramethyl-6-(1 methyl-2- phenylethenyl)naphthalene and its phenolic metabolite in human plasma by reversed-phase high-performance liquid chromatography. AB - A rapid, sensitive and specific high-performance liquid chromatographic assay was developed for the determination in plasma of (E)-1,2,3,4-tetrahydro-1,1,4,4 tetramethyl-6-(1-methyl-2- phenylethenyl)naphthalene (1) and its phenolic metabolite (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-2- methylethenyl]-phenol (2). An extraction procedure using protein precipitation and liquid-liquid extraction was combined with a simple column-switching technique. To minimize sample consumption, the assay was adapted to a sample volume of 200 microliters, which was sufficient for more than 90% of all determinations. The quantification limit was 100 ng/ml for 1 and 2, whereas the detection limits were 20 and 30 ng/ml, respectively. The recoveries for 1 and 2 were 91 and 94%, respectively, using ultraviolet detection at 280 nm. The assay was used to quantify both compounds in human plasma samples. PMID- 1874882 TI - Sensitive microbore high-performance liquid chromatographic assay for labetalol in the biological fluids of pregnant sheep. AB - A rapid and sensitive microbore high-performance liquid chromatographic (HPLC) assay is reported for the quantitation of labetalol, an anti-hypertensive agent, in small volumes (250 microliters) of biological fluids (viz., maternal plasma, fetal plasma, amniotic fluid and fetal tracheal fluid) obtained from the chronically instrumented pregnant sheep. Labetalol was extracted from the samples using ethyl acetate and then partitioned into dilute phosphoric acid. Chromatography was performed on a microbore HPLC system using a 2.1 mm I.D. C18 column and detection was accomplished by a low-dispersion fluorescence detector designed for trace analysis. The drug was well separated from endogenous substances in all biological fluids sampled. The calibration curves were linear for all fluids over the range of study with mean coefficients of variation consistently below 5%. Quantitation was possible down to approximately 30 pg of labetalol injected (approximately 1.6 ng/ml in plasma using 250 microliters). PMID- 1874883 TI - Determination of [3H]brifentanil, a potent narcotic analgesic, from rat serum by high-performance liquid chromatography with on-line radioactive detection. AB - A method for rapid analysis of [3H]brifentanil extracted from rat serum is described that has the advantages of sensitivity, speed and specificity. The method is based on extraction from serum via solid-phase extraction followed by chromatographic separation on a reversed-phase high-performance liquid chromatographic column. Detection of [3H]brifentanil is accomplished with an on line radioactive detector, thus the laborious step of peak collection and subsequent liquid scintillation counting is eliminated. The developed method is sensitive to 0.1 ng/ml and has been successfully applied to pharmacokinetic studies in rats. In vivo metabolites retaining the radiolabel have been detected with the method and were more polar than the parent compound as based upon the elution order on the reversed-phase system. PMID- 1874884 TI - Determination of diclofenac in plasma using a fully automated analytical system combining liquid-solid extraction with liquid chromatography. AB - A fully automated analytical system based on liquid-solid extraction combined with column liquid chromatography is described for the determination of diclofenac in plasma. After addition of pH 5 buffer and the internal standard solution to the plasma sample, both sample preparation via a C18 disposable extraction column and injection were performed by a Gilson ASPEC system. Diclofenac and the internal standard were separated on a reversed-phase column, using methanol-pH 7.2 phosphate buffer (56:44, v/v) as mobile phase at a flow rate of 0.4 ml/min. The reproducibility and accuracy of the method were acceptable over the concentration range 31-3140 nmol/l in plasma. PMID- 1874885 TI - Liquid chromatography-mass spectrometry for simultaneous analyses of iminodipeptides containing an N-terminal or a C-terminal proline. AB - Simultaneous analyses of synthetic iminodipeptides containing an N-terminal proline or a C-terminal proline have been demonstrated using liquid chromatography-mass spectrometry with an atmospheric pressure ionization interface system. The separation of iminodipeptides was carried out on a reversed phase high-performance liquid chromatographic column using 0.1% aqueous trifluoroacetic acid-methanol (75:25, v/v, pH 2.0) as mobile phase. Very intense protonated molecular ions [M + H]+ of various synthetic iminodipeptides, Pro-Gly, Gly-Pro, Pro-Ala, Ala-Pro, Pro-Val, Val-Pro, Pro-Leu and Leu-Pro, were observed. Pro-Gly (Pro-X) and Gly-Pro (X-Pro) have the same protonated molecular ion (m/z 173), but the peaks of these compounds on the mass chromatograms were clearly distinguished by the differences of the retention times and mass spectra. The synthetic iminodipeptides containing an N-terminal proline added to urine samples from a patient with prolidase deficiency were also distinguished from iminodipeptides containing a C-terminal proline in urine samples from a patient with prolidase deficiency by scanning the [M + H]+ ion of each iminodipeptide. We established the method to measure simultaneously the various iminodipeptides containing an N-terminal or a C-terminal proline in biological samples. PMID- 1874886 TI - Novel affinity chromatographic system for the single-step purification of glycosaminoglycans from complex systems using volatile buffers. AB - A new system for the isolation and purification of glycosaminoglycans (GAGs) and related molecules from complex systems such as plasma is described. Affinity chromatography which exploits the very high affinity between the polymeric base Polybrene and sulphated polysaccharides was used. A novel volatile buffer system composed of ammonium formate and formic acid, which allows the complete recovery of samples, was developed, and elution conditions were optimised for the separation and purification of GAGs of different charge densities. Using this system the losses associated with dialysis and desalting, frequently necessary preliminaries to further analysis, are avoided. PMID- 1874887 TI - High-performance liquid chromatographic analysis of free palmitic and stearic acids in cerebrospinal fluid. AB - A relatively simple method for extraction of free fatty acids from cerebrospinal fluid with aminopropyl bonded-phase columns, and the estimation of palmitic acid (C16:0) and stearic acid (C18:0) concentrations by high-performance liquid chromatographic analysis is described. The values of C16:0 and C18:0 in patients with non-neurological disorders lie within a narrow range, with a mean (+/- S.D.) of 4.02 +/- 0.33 micrograms/ml for C16:0 and 2.72 +/- 0.39 micrograms/ml for C18:0. PMID- 1874888 TI - Improved method for the determination of serotonin in plasma by high-performance liquid chromatography using on-line sample pre-treatment. AB - An improved method for the determination of serotonin in platelet-rich plasma (PRP) and platelet-poor plasma (PPP), by reversed-phase high-performance liquid chromatography with electrochemical detection and direct plasma injection, is described. The chromatographic system comprises a strong cation-exchange pre column and a C18 analytical column. The method is selective, rapid, simple and sensitive, and offers good reproducibility and recovery. Reference values for serotonin concentrations in healthy adults (n = 10) are 31 nM for PPP and 6 nmol per 10(9) platelets for PRP. The conditions used for the preparation of PRP and PPP may influence the serotonin concentration in PRP. PMID- 1874889 TI - Determination of 3-hydroxykynurenine in human brain and plasma by high performance liquid chromatography with electrochemical detection. Increased concentrations in hepatic encephalopathy. AB - A simple and specific method was developed for the determination of 3 hydroxykynurenine in brain tissue and blood plasma using high-performance liquid chromatography with electrochemical detection. This involved an extraction procedure using strong cation-exchange columns and also permitted the determination of 3-hydroxyanthranilic acid in brain tissue. The method was applied to the investigation of post mortem brain tissue from patients with hepatic encephalopathy. Cortical 3-hydroxykynurenine concentrations were substantially increased in such patients above control values, providing evidence for a dysfunction of tryptophan metabolism in this disease. PMID- 1874890 TI - Rapid high-performance liquid chromatographic assay for total homocysteine levels in human serum. AB - A rapid, isocratic high-performance liquid chromatographic (HPLC) method is described for the determination of total homocysteine levels in human serum. Prior to reversed-phase HPLC analysis, the serum thiols were derivatized with SBD F (ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate), a thiolspecific fluorogenic probe which is commercially available. Retention of SBD-homocysteine was sensitive to pH, and a mobile phase pH of 2.1 ensured baseline separation of serum thiols within 6 min. The method is simple, sensitive, reproducible (between run coefficient of variation of 6.6%) and very suitable for routine determination of serum homocysteine levels in a clinical pathology laboratory. PMID- 1874891 TI - Simple method for the determination of inorganic sulfate in human serum and urine using single-column ion chromatography. AB - A single-column ion chromatographic assay with conductivity detection was developed to determine inorganic sulfate concentrations in human plasma and urine samples. Plasma samples were ultrafiltered to remove proteins. Plasma ultrafiltrate and urine samples were diluted prior to injection onto the anion exchange column. The described method is simple, fast, sensitive and reproducible and was used to study the effect of subchronic administration of acetaminophen on the plasma concentrations and urinary excretion of inorganic sulfate in healthy volunteers. PMID- 1874892 TI - Characterization of prednisone, prednisolone and their metabolites by gas chromatography-mass spectrometry. AB - Human urinary metabolites of the synthetic corticosteroids prednisone and prednisolone were detected in the course of gas chromatographic steroid profiling as methoxime-trimethylsilyl derivatives. Metabolites were provisionaly identified by combined gas chromatography-mass spectrometry. The major metabolites were 11 keto/11-hydroxy conversion products, 20-hydroxy and 4,5-dihydro analogues of the parent drugs. Cortisone, 6-hydroxy and fully saturated A-ring compounds were minor metabolites. Retention indices and mass spectral data are presented. PMID- 1874893 TI - Determination of dimethyl sulphide in blood and adipose tissue by headspace gas analysis. AB - A method for the headspace analysis of dimethyl sulphide in blood and adipose tissue has been established. Blood (0.2 ml) or adipose tissue (0.5 g) with added dimethyl sulphide was sealed in a 10-ml vial using PTFE sheet to prevent escape of dimethyl sulphide from the headspace. Equilibration was performed at 60 degrees C for 4 h, and 20 microliters of gaseous phase sampled from the headspace was subjected to gas chromatography (with flame photometric detection). Calibration curves were prepared for the two samples. Linearity was observed in the range from 5-10 micrograms to 2 mg. PMID- 1874894 TI - High-performance liquid chromatographic determination of morphine and its 3- and 6-glucuronide metabolites: improvements to the method and application to stability studies. AB - Improvements to previously reported methods for the determination of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in human plasma are described. The improved methods involve the use of a solid-phase extraction cartridge and a chromatographic system which uses paired-ion reversed-phase high performance liquid chromatography with a radially compressed column. Only one cartridge is used to prepare each sample for chromatography and each cartridge may be used for at least fourteen 1-ml plasma samples. The recovery is greater than 85%. The improvements to the method of sample pretreatment and in the chromatographic conditions have allowed determination of morphine, M3G and M6G in human plasma down to 13.3 nmol/l (coefficient of variation = 9.3%), 108 nmol/l (6.6%) and 41 nmol/l (6.7%), respectively, using ultraviolet detection alone. It was shown that all three compounds were stable in plasma for up to 101 weeks when stored at -20 degrees C. PMID- 1874895 TI - High-performance liquid chromatographic assay for laudanosine in biological fluids and tissue for neurotoxic studies in rats. AB - A procedure for the determination of laudanosine, the central nervous system active metabolite of the neuromuscular blocking drug atracurium, in serum, cerebrospinal fluid and brain is described. The method uses a readily available internal standard, ethavrine, and a single-step protein precipitation with acetonitrile followed by high-performance liquid chromatographic separation with ultraviolet detection. Norlaudanosine, the major metabolite of laudanosine, can also be quantified. Linearity of detector response was obtained between 1 and 25 micrograms/ml or micrograms/g and the method is suitable for determining neurotoxic concentrations of laudanosine in experimental animals. PMID- 1874896 TI - Determination of thiamphenicol residues in chicken muscles by column liquid chromatography. AB - A column liquid chromatographic (CLC) method for the determination of thiamphenicol residues in chicken muscles was developed. The drug is extracted from minced muscles with ethyl acetate and the extract is evaporated to dryness. The residue is dissolved in 10% sodium chloride solution and partitioned with n hexane. Thiamphenicol is extracted with ethyl acetate and, after evaporation of the solvent, the residue is cleaned up by alumina column chromatography. CLC analysis is carried out on a Nucleosil C18 column with ultraviolet detection of thiamphenicol at 230 nm. The average recoveries of thiamphenicol added to muscles at 0.2 and 0.1 ppm were 92.8 and 90.0%, respectively. The detection limit was 5 ng for thiamphenicol standard, which corresponds to 0.05 ppm in muscles. PMID- 1874897 TI - Determination of amidepin in human plasma by reversed-phase high-performance liquid chromatography with fluorescence detection. AB - An isocratic reversed-phase high-performance liquid chromatographic method for the determination of amidepin has been developed. The method is based on the extraction of alkaline plasma with diethyl ether-dichloromethane, and the injection into the Supelcosil LC-18 column of the evaporated and reconstituted organic phase. After separation, detection is carried out by a fluorescence detector (excitation at 195 nm with no filter). The limit of detection is 10 ng/ml of plasma. The mean coefficient of variation is 12%. The plasma levels after oral administration and after intravenous administration are shown. PMID- 1874898 TI - Determination of alentamol hydrobromide, a novel antipsychotic agent, in human blood plasma and urine by high-performance liquid chromatography with fluorescence detection and solid-phase extraction. AB - Alentamol hydrobromide, (+)-2-(dipropylamino)-2,3-dihydro-1H-phenalen-5-ol monohydrobromide, is a selective dopamine agonist currently being investigated for the treatment of schizophrenia. This paper describes a reversed-phase high performance liquid chromatographic-based method for the quantification of alentamol in blood plasma and urine. The method utilizes solid-phase extraction with carboxylic acid-derivatized silica columns. A limit of quantitation of 0.1 ng/ml in plasma was achieved by virtue of selective extraction and fluorescence detection. Example chromatograms of plasma and urine specimens from clinical trials demonstrate the utility of the method. PMID- 1874899 TI - Pirmenol determination by high-performance liquid chromatography. AB - A method for the determination of pirmenol in serum is presented in this paper. The method consists of extraction of pirmenol and chlorodisopyramide (internal standard) from serum at an alkaline pH using methylene chloride. The organic extract was analysed using high-performance liquid chromatography. The mobile phase consisted of 0.01 M K2HPO4 (pH 2.4)-acetonitrile (94:6, v/v) delivered at ambient temperature and 2 ml/min through a 25 cm x 0.4 mm C18 reversed-phase column. Detection of the compounds of interest was achieved at 210 nm. The analytical method demonstrated low intra- and inter-assay variation. During the analysis of patient samples and a therapeutic drug mixture test serum, no substances that interfered with pirmenol detection were found. The method is shown to be stable, accurate, selective and sensitive enough to be utilized for the analysis of multiple samples such as may be encountered in clinical or research situations. PMID- 1874900 TI - Sensitive determination of free and plasma protein-bound dipyridamole by high performance liquid chromatography. AB - For many years dipyridamole (DP) has been used in the treatment of hypertension as a vasodilator, but recently it has been recognised as an anti-platelet aggregation agent and to potentiate anti-metabolite activity. A rapid and sensitive (20 nM) procedure for the determination of free and protein-bound DP in plasma, using reversed-phase high-performance liquid chromatography on an Ultrasphere XL ODS (3 microns) column (70 mm x 4.6 mm I.D.) with ultraviolet detection (280 nm), is reported. Free and bound DP were separated using ultrafiltration. Concentrations of DP between 0.1 and 10 microM were measured in plasma with a relative standard deviation of less than 9.6%. The subsequent determination of DP levels in patients orally administered 450 mg per day showed that DP binding to plasma protein is higher than 90%. PMID- 1874901 TI - High-performance liquid chromatographic determination of the polar metabolites of nifedipine in plasma, blood and urine. AB - A relatively simple reversed-phase high-performance liquid chromatographic method for the determination of the polar metabolites of nifedipine in biological fluids is described. After conversion of 2-hydroxymethyl-6-methyl-4-(2 nitrophenyl)pyridine-3,5-dicarboxylic acid 5-methyl ester (IV) into 5,7-dihydro-2 methyl-4-(2-nitrophenyl)-5-oxofuro[3,4-b] pyridine-3-carboxylic acid methyl ester (V) by heating under acidic conditions, V was extracted with n-pentane dichloromethane (7:3) and analysed on a C18 column with ultraviolet detection. Subsequently, 2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid monomethyl ester (III) was extracted with chloroform and analysed on the same system. Limits of determination in blood were 0.1 microgram/ml for III and 0.05 microgram/ml for IV and V; these limits were two to ten times higher for urine. This inter-assay variability was always less than 7.5%. PMID- 1874902 TI - Simplified procedure for the determination of sotalol in plasma by high performance liquid chromatography. AB - A simple, specific and rapid reversed-phase high-performance liquid chromatographic (HPLC) procedure for sotalol determination is described requiring small plasma volumes. The high recovery of sotalol from plasma and the high precision of measurement obviate the need for an internal standard. Plasma samples (300 microliters) were deproteinised with 50 microliters of 70% (w/w) perchloric acid in disposable glass tubes. After vortex-mixing and centrifugation, 30 microliters of 4 M K2HPO4 were added followed by gentle shaking. A 20-microliters aliquot was then injected (by autosampler) for HPLC analysis. Chromatography was performed on a glass-lined 250 mm x 4 mm 5-micron C18 steel column. The mobile phase was 6% (v/v) acetonitrile in 0.08 M KH2PO4 buffer (pH 4.6). The flow-rate was 0.8 ml/min. Detection was by fluorescence with excitation and emission wavelengths at 235 and 310 nm, respectively. The retention time for sotalol was 7.1 min. Calibration was linear from 0.16 to 10 micrograms/ml in plasma (r greater than 0.999 for detector response to sotalol). The minimum concentration for quantitation was 0.08 micrograms/ml [within assay coefficient of variation (C.V.) less than 5%]. Recovery was near quantitative (greater than 98%) and replicate (intra-assay precision was less than 5% C.V.). Analysis of samples (n = 10) at concentrations of 0.42 and 4.2 micrograms/ml gave mean values of 0.44 and 4.3 micrograms/ml, respectively. The inter-assay C.V. values were 4.5 and 2.2%, respectively. Other clinically used antiarrhythmic drugs did not interfere. This assay can be performed using other commercial C18 analytical columns by suitable adjustment of mobile phase flow-rate and acetonitrile composition. PMID- 1874903 TI - Simultaneous high-performance liquid chromatographic determination of ascorbic acid and dehydroascorbic acid in biological samples. AB - The ascorbic acid (AA)-dehydroascorbic acid redox couple is an important component of many biological systems, and various physiological roles have been described for this vitamin. Simultaneous measurement of both AA and dehydroascorbate using high-performance liquid chromatography (HPLC) has proven difficult owing to detection problems. A simple, single-step HPLC assay for the simultaneous detection of both AA and dehydroascorbate was developed without the burden of derivatization of either compounds. This has proven to be a reliable technique and should be applicable to a wide variety of biological samples. PMID- 1874904 TI - Simultaneous assay of the activities of two key enzymes in cholesterol metabolism by gas chromatography-mass spectrometry. AB - A very sensitive and specific method for the simultaneous assay of the activities of two key regulatory enzymes in cholesterol metabolism, 3-hydroxy-3 methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34), and cholesterol 7 alpha-hydroxylase (EC 1.14.13.7), is described. The assay is based on the measurement of [2H3]mevalonolactone and 7 alpha-hydroxycholesterol produced by the incubation of [2H3]HMG-CoA and endogenous cholesterol with hamster liver microsomes using isotope dilution mass spectrometry. The incubation mixture was purified by means of solid extraction cartridges, and the extract was treated with benzylamine followed by dimethylethylsilyl imidazole. The resulting ether derivatives of the mevalonylbenzylamide and 7 alpha-hydroxycholesterol were quantified by gas chromatography-mass spectrometry with selected-ion monitoring in a high resolution mode. The method made it possible to assay simultaneously the activities of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in hamster liver microsomes with high sensitivity and accuracy. PMID- 1874905 TI - Determination of 4-hydroxyandrostenedione in plasma and urine by extractive alkylation and electron-capture gas chromatography. AB - A sensitive and specific quantitative assay has been developed for the determination of 4-hydroxyandrostenedione (4-OHA), a potent aromatase inhibitor used in the treatment of estrogen-dependent breast cancer. This steroid has a high first-pass metabolism and is extensively metabolized, mainly by glucuronidation. Plasma levels of unchanged 4-OHA are very low, even after high peroral doses. The analytical method is based on the addition of 17 alpha ethinylestradiol (internal standard), liquid-liquid extraction from biological material followed by extractive alkylation with pentafluorobenzyl bromide and quantitation by gas chromatography. The method has been validated for sensitivity, accuracy and precision and was found to be suitable for application to pharmacokinetic and bioavailability studies of peroral formulations of 4-OHA. PMID- 1874906 TI - Determination of 4-hydroxyandrost-4-ene-3,17-dione metabolism in breast cancer patients using high-performance liquid chromatography-mass spectrometry. AB - A sensitive procedure for studying the metabolism of the steroidal aromatase inhibitor 4-hydroxy-androst-4-ene-3,17-dione (4OHA) was developed based on enzyme hydrolysis, liquid-liquid extraction and reversed-phase liquid chromatography coupled with a mass spectrometer (LC-MS) using a thermospray interface. Seven metabolites were identified from the hydrolysed urine samples together with the parent drug. The major routes of metabolism were via dehydrogenation, reduction of the ketone functional groups, reduction at the C-4-C-5 double bond and hydroxylation at the C-5 position. Confirmation of the identity of 4OHA and its metabolites isolated from female patients' urine samples was accomplished by comparison of the retention times of their corresponding synthetic standards on LC-MS. We have demonstrated that this technique is particularly suitable for studying the metabolism of steroidal drugs. PMID- 1874907 TI - Assay methodology for prednisolone, prednisolone acetate and prednisolone sodium phosphate in rabbit aqueous humor and ocular physiological solutions. AB - Prednisolone, prednisolone acetate and prednisolone sodium phosphate are glucocorticoids used for ocular, anti-inflammatory therapy. A reversed-phase high performance liquid chromatographic assay using ultraviolet detection has been developed that affords baseline resolution of the above analytes in balanced salt solutions and rabbit aqueous humor. The drugs can be quantified at 0.025-0.05 micrograms/ml in the above matrices; 6 alpha-methylprednisolone is used as the internal standard. Both esters of prednisolone are vulnerable to chemical and enzymatic hydrolysis giving prednisolone. Analysis of aqueous humor samples shows prednisolone acetate penetrating/metabolizing primarily to prednisolone; prednisolone sodium phosphate penetrates the cornea giving the ester and alcohol. PMID- 1874908 TI - The determination of nitroaromatics and nitramines in ground and drinking water by wide-bore capillary gas chromatography. AB - A method has been developed to determine the concentration of nitroaromatics and nitramines in drinking water at levels below those previously achieved by gas chromatography. The nitroaromatics and nitramines are extracted from water using toluene and isoamyl acetate, respectively. The extracts are analyzed via a gas chromatograph equipped with a DB-1301 widebore fused-silica capillary column and an electron capture detector. Method detection limits of 0.003 micrograms/L for 2,6-dinitrotoluene (2,6-DNT), 0.04 micrograms/L for 2,4-dinitrotoluene (2,4-DNT), 0.06 micrograms/L for 2,4,6-trinitrotoluene (TNT), 0.3 micrograms/L for cyclotrimethylenetrinitramine (RDX), and 6.0 micrograms/L for cyclotetramethylenetetranitramine (HMX) have been obtained using this method. PMID- 1874909 TI - Influence of the mobile phase on salmon calcitonin analysis by reversed-phase liquid chromatography. AB - The retention properties of calcitonins on a reversed-phase column are examined using salmon calcitonin as the model compound. The effect of the concentration of organic modifier, buffer strength, pH of the mobile phase, and ion-pair reagent are studied. In the absence of an ionic modifier in the eluent the calcitonin peak shapes are not symmetrical. The addition of 0.1% trifluoroacetic acid (TFA), however, results in good peak characteristics without the need to add nonvolatile salts. The retention of the calcitonins was found to be very sensitive to the concentration of the organic modifier (acetonitrile) present in the mobile phase. A change of pH between 2 and 5 has only a slight effect of the k' of salmon calcitonin, but the k' increases significantly at higher pH values. The addition of a phosphate buffer to the mobile phase and an increase in the buffer concentration (0-0.2 M) causes a decrease in the retention of salmon calcitonin. Evidence shows that reproducible, quantitatively measurable data can be obtained using reversed-phase chromatography if the ion-pairing reagent and organic modifier concentrations are carefully controlled. The system also shows a good selectivity for the calcitonin series. Therefore, both highly selective methods (qualitative) as well as quantitative methods for analytical, pharmaceutical, and manufacturing use can be developed by adjusting the high-performance liquid chromatography (HPLC) conditions as discussed. PMID- 1874910 TI - Graphitized carbon black in quartz tubes for the sampling of indoor air nicotine and analysis by microwave thermal desorption-capillary gas chromatography. AB - Nicotine in a smoky indoor air environment can be determined using graphitized carbon black as a solid sorbent in quartz tubes. The temperature stability, high purity, and heat absorption characteristics of the sorbent, as well as the permeability of the quartz tubes to microwaves, enable the thermal desorption by means of microwaves after active sampling. Permeation and dynamic dilution procedures for the generation of nicotine in the vapor phase at low and high concentrations are used to evaluate the performances of the sampler. Tube preparation is described and the microwave desorption temperature is measured. Breakthrough volume is determined to allow sampling at 0.1-1 L/min for definite periods of time. The procedure is tested for the determination of gas and paticulate phase nicotine in sidestream smoke produced in an experimental chamber. PMID- 1874911 TI - Silica gel high-performance liquid chromatography for the determination of cross links in elastin. AB - A high-performance liquid chromatographic (HPLC) procedure for the determination and preparation of desmosine (DES) and isodesmosine (IDE), the major cross-links of elastin, has been developed. Hydrolysates of elastin are treated with a SEP PAK silica-gel small column and then separated on a silica-gel normal phase column using n-propanol-water-25% ammonia (9:3:0.06, v/v/v) followed by detection at 275 nm. The quantitative yields of DES and IDE are 7.98 +/- 0.47 and 6.44 +/- 0.51 (mean +/- S.D., n = 10) mg/g dry weight, respectively, in bovine ligamentum nuchae. Preparations of cross-links are carried out by means of a preparative column (240 mm x 10 mm), using the same solvent system. PMID- 1874912 TI - Microwave radiation: a useful fixation method for viral vaccine quantitation. AB - As an alternative to the formalin fixation of cells before staining, microwave irradiation was found a very advantageous fixation procedure in viral vaccine quantitation assays. The use of microwaves allows to avoid dangerous chemicals and thereby reduces time and equipment. PMID- 1874913 TI - Methods for detecting arctic rabies virus in dilution series of field samples. AB - A modified first passage cell culture method, mouse inoculation test, and ELISA were compared for the detection of rabies in serially diluted field samples. Each original specimen contained rabies antigen, individually identified as an arctic strain by monoclonal antibodies. In 47% of the samples tested in cell cultures, the end-point titer was increased as a result of the first passage. The cell culture method gave higher titers than the mouse inoculation test or ELISA (P less than 0.05 and P less than 0.01, respectively). PMID- 1874914 TI - The use of antibiotics to control bacterial overgrowth of cell cultures used for diagnostic virology. AB - Although penicillin and streptomycin are added routinely to cell culture media, bacterial overgrowth has caused a significant problem. A total of 34.4% cell cultures inoculated with specimens, from immunocompromised patients for the isolation of viruses, was discontinued because of bacterial overgrowth. When ceftazidime and vancomycin were added to inoculated cell cultures the overall proportion of contaminated cultures fell from 16.3 to 0.6% (P less than 0.001). The proportion of cell cultures contaminated after inoculation with specimens from immunocompromised patients fell from 34.4 to 0.4% (P less than 0.001). At the same time the isolation rate of herpes viruses from specimens submitted from immunocompromised patients increased from 5.2 to 16.4% (P less than 0.001). PMID- 1874915 TI - An enzyme immunoassay for detection of IgA class antibodies against hepatitis delta virus. AB - A sensitive and reproducible enzyme-linked immunoassay (ELISA) for IgA class antibodies against the Delta antigen (HDAg) is described. Specificity of the assay was demonstrated by the absence of binding to an unrelated antigen or to uncoated plates and the finding that binding to HDAg was independent of total IgA concentrations in sera. Positive results were obtained with sera from 11 of 14 patients with chronic Delta virus infection (seropositive for HBsAg and IgM anti HDAg, negative for IgM anti-HBc) at serum dilutions of up to 1:10(6). Sera from four normal healthy individuals and from 25 patients with chronic hepatitis B or other liver disorders who had no evidence of exposure to HDV were all negative in the assay. PMID- 1874916 TI - Polymerase chain reaction (PCR) amplification for the detection of porcine parvovirus. AB - A polymerase chain reaction (PCR) amplification method was developed and evaluated to detect porcine parvovirus (PPV). A pair of 20-base primers and an oligonucleotide probe were derived from the DNA sequences common to two isolates of PPV, NADL-8 and NADL-2. The primers flanked 118-bp nucleotides within the region coding for the major structural protein VP2. After DNA amplification of PPV replicative form (RF), a 158-bp fragment was detected in agarose gels. This amplified fragment was shown to be specific for PPV DNA after Southern transfer and hybridization to a 20-base internal probe. The amplified fragment also contained a single EcoRI cleavage site. Various conditions, such as number of cycles and annealing temperature, were examined to optimize the conditions for detecting viral DNAs from infected cell cultures and swine fetal tissues. Four different isolates of PPV, NADL-8, NADL-2, KBSH and Kresse, and two other viruses, canine parvovirus (CPV) and pseudorabies virus (PRV), were included to determine specificity of amplification. Slot blot hybridization with a radiolabeled probe was used to evaluate the sensitivity of PCR amplification. The optimized protocol was specific for PPV detecting equally all four strains of PPV, but failing to amplify CPV or PRV sequences. The PCR method could detect at least 100 fg of viral replicative form (RF) DNA or the equivalent of 1 PFU of infectious virus. The applications of this method include routine detection of PPV in clinical samples and as a contaminant in mammalian cell lines. PMID- 1874917 TI - Assay of anti-HBs antibodies using a recombinant antigen and latex particle counting: comparison with five commercial tests. AB - An assay of anti-HBs antibodies based on agglutination of latex particles coated with recombinant HBs-antigen was compared with Abbott radioimmunoassay (Abbott RIA), which uses a human plasma-derived antigen. The population examined consisted of 76 Abbott-RIA anti-HBs-negative prevaccinated subjects and 1044 serum samples anti-HBs found positive by Abbott-RIA, including 283 samples of subjects vaccinated either with a human plasma-derived vaccine (group A; n = 180) or with a recombinant vaccine (group B; n = 103). Correlation coefficients between the two techniques were respectively r = 0.89 for the whole population (n = 1044), r = 0.98 in group A and r = 0.74 in group B. Anti-HBs titres were higher with latex than with RIA in group B as shown by the regression slopes: latex = 508 + 1.11 RIA in group A and latex = -1138 + 3.97 RIA in group B, suggesting that some vaccinated subjects from group B produced antibodies against epitopes proper to the recombinant antigen. In the prevaccinated population and in group A, the latex results were compared with those of radioimmunoassays (Abbott, Sorin) and enzyme immunoassays (Behring, Roche, Pasteur). Only the Roche-EIA detected anti-HBs in the prevaccinated subjects. The correlation between the various immunoassays was r greater than 0.96 only for values higher than 100 IU/l. PMID- 1874918 TI - A rapid chemiluminescence detection method for PCR-amplified HIV-1 DNA. AB - A solution hybridization assay using acridinium ester labelled probes is described for detection of amplified HIV-1 DNA segments. Amplification was achieved by 30 cycles of the polymerase chain reaction using SK38/SK39 primers specific for a constant region of the HIV-1 gag region together with HLA DQ alpha primers as internal control. Discrimination between hybridized and non-hybridized probes by differential hydrolysis resulted in a three log reduction of the chemiluminescence signal of the non-hybridized probe within 6 min without significant changes in the hybridized probes due to protection of the acridinium ester to hydrolysis by intercalation formation. Chemiluminescence was measured by a two-step-injection method with hydrogen-peroxide and NaOH. About 50 attomols of HIV-1 gag DNA could be detected. Chemiluminescence results, given in relative light units (RLU) of 159 HIV-1-infected patients (range 4013-458319) showed clear discrimination from 64 noninfected control samples (range 838-1477) (cut off 2000 RLU). Comparison with parallel detection of amplified products with autoradiography (32P) and ethidium bromide-stained agarose gels or a p24 antigen ELISA demonstrated better sensitivity and reproducibility of the chemiluminescence assay. The time required for the assay, including measurements, is less than 30 min, which allows reporting 'PCR results' on the same day. PMID- 1874919 TI - Quantitation of hepatitis B surface antibody by an automated microparticle enzyme immunoassay. AB - A fully automated microparticle enzyme immunoassay, IMx AUSAB, was developed for the detection and quantitation of antibody against hepatitis B surface antigen (anti-HBs). The IMx AUSAB assay can complete 24 tests in less than 45 minutes. Anti-HBs concentrations in specimens are calculated automatically by comparison of the specimen rate to values determined from a stored standard curve. IMx AUSAB sensitivity is 2-3 mIU/ml, equivalent in sensitivity to AUSAB RIA or EIA. Specimens from blood donors, diagnostic and hospital patients, hepatitis B vaccinees, and individuals with a variety of infectious and autoimmune diseases tested in parallel by IMx AUSAB and AUSAB RIA or IMx AUSAB and EIA gave overall qualitative agreement of 97.8% (1265/1293) and 99.1% (1281/1293), respectively. The prevalence of anti-HBs ranged from 5.9% in volunteer blood donors to 47.0% of specimens from a sexually transmitted disease clinic. Most discordant specimens (18/34) were low level reactive (less than 10 mIU/ml) by AUSAB RIA, but negative by IMx AUSAB and AUSAB EIA. These specimens were also negative for antibodies to hepatitis B core antigen (anti-HBc). Six discordants were low level reactive by IMx but negative by RIA and EIA. Three of these six specimens were also reactive for anti-HBc suggesting that the IMx AUSAB reactivity resulted from the presence of low level anti-HBs. Quantitative agreement between IMx AUSAB and RIA or IMx and EIA for 106 specimens ranging in anti-HBs concentration from 1 to 30,000 mIU/ml gave linear correlation coefficients of 0.91 and 0.96, respectively. The IMx test was useful for monitoring hepatitis B vaccine response and seroconversion levels after hepatitis B infection. PMID- 1874920 TI - A simple and rapid method for detecting human immunodeficiency virus by PCR. AB - A simple, sensitive and specific method using the polymerase chain reaction (PCR) for amplification of human immunodeficiency virus type 1 (HIV-1) is described. The method involves minimal manipulations. Peripheral blood mononuclear cells (PBMC) were prepared by a rapid Ficoll-Paque gradient method. Lymphocytes were lysed in PCR buffer containing Proteinase K and detergents, and subjected to amplification under stringent conditions, using two primer pairs. Amplified DNA sequences were hybridized with a 3'-end labelled probe, electrophoresed on agarose gels and visualised by ethidium bromide staining. Identification of amplified HIV-1 proviral DNA sequences was confirmed by autoradiography. HIV-1 sequences were amplified in all samples from 103 HIV-1 seropositive individuals, but not in 40 HIV-1 seronegative controls. The absence of contamination may be attributable in part to minimisation of manipulations before amplification. PMID- 1874921 TI - Human immunodeficiency virus: novel enzyme-linked immunoassays for quantitation of envelope glycoprotein 120. AB - Two novel enzyme-linked immunoassays (ELISA) for the quantitation of human immunodeficiency virus type 1 (HIV-1) coded glycoprotein with an Mr 120 (gp120) are described. These are based on the highly specific interaction between gp120 and the mannose-specific lectins from Narcissus pseudonarcissus (NPL) and Galanthus nivalis (GNL). Two systems were developed: (1) an HIV-protein ELISA using HIV-protein (also containing HIV-gp120) for the solid phase and NPL as a detector and (2) a lectin-ELISA using the NPL bound to the solid phase and GNL as detector. The HIV-protein ELISA was validated for quantitation of gp120 within the range 3 to 600 ng/ml; the lectin-ELISA for concentrations between 0.6 and 20000 ng gp120/ml. Serum components did not interfere with the binding of gp120 to the lectins. The ELISAs were used for the quantitation of gp120 in HIV infected CEM cells in vitro. It was found that gp120 appeared in the medium earlier after infection than HIV-p24 and reverse transcriptase, suggesting that gp120 is released as free glycoprotein. Moreover, the ELISAs were also applied successfully for the detection of compounds that bind to gp120 and for the identification of antibodies directed against the highly pathogenic mannan portion of gp120. These ELISAs are considered to be suitable also for the detection of gp120 in the serum of HIV-infected individuals. PMID- 1874922 TI - Large-scale purification of gp70 from Moloney murine leukemia virus. AB - The external envelope glycoprotein, gp70, of the Moloney murine leukemia virus was extracted from NIH 3T3 cells utilizing the detergent n-octyl-beta-D glycopyranoside. The extracted gp70 was sequentially purified utilizing lectin affinity, anion-exchange, and molecular-exclusion chromatography techniques. Approximately 10 mg of gp70 was purified by this method and shown to be 95% homogeneous, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The presence of purified gp70 from Moloney murine leukemia virus was confirmed by amino acid analysis, amino-terminal sequencing, and immunoreactivity with a monoclonal antibody raised against gp70. The procedure is rapid, utilizes commercially available media, and can be used to purify large amounts of retroviral envelope glycoprotein from virus. PMID- 1874923 TI - Clinical review 25: Current status of pancreas transplantation. PMID- 1874924 TI - Hormonally-based male contraceptives: will they ever be a reality? PMID- 1874925 TI - Gonadotropin-releasing hormone antagonist plus testosterone: a potential male contraceptive. AB - No effective hormonal contraceptive has yet been devised for men. Through their suppressive effect on gonadotropin secretion, GnRH antagonists inhibit both testosterone (T) production and spermatogenesis in animals. Long term administration of an antagonist alone would result in androgen deficiency; this would cause unacceptable physiological and behavioral sequellae in men. Therefore, androgen replacement must be included in any GnRH antagonist regimen used in human male contraception. We tested the hypothesis that the combination of a GnRH antagonist plus T would suppress spermatogenesis in the male primate to azoospermic levels while maintaining normal serum T levels. We examined the effects of the GnRH antagonist Deterelix [N-Ac-DNal(2)1-DpCl-Phe2-DTrp3 DhArg(Et2)6 -DAla10-GnRH], alone and with simultaneous T replacement, on sperm production and serum T levels in adult male monkeys (n = 22). After 12 weeks of daily sc antagonist injection, all animals that received antagonist alone (n = 5) and those that 750 micrograms/kg.day antagonist plus T (n = 5) were azoospermic. After 16 weeks, four of five animals that received 250 micrograms/kg.day antagonist plus T became azoospermic. Control animals (n = 7) received daily injections of vehicle; sperm counts increased somewhat during the study period in that group. Castrate range T levels were achieved in animals receiving antagonist alone. T levels in the groups that received T supplementation and in the control group were in the normal male range throughout the treatment period. Sperm counts returned to the pretreatment range in all animals during the recovery period. We conclude that the combination of a GnRH antagonist plus T can induce azoospermia reversibly in this nonhuman primates species, and that a similar combination may be an effective contraceptive regimen in men. The GnRH antagonist alone may be an effective treatment for androgen-dependent neoplasia. PMID- 1874926 TI - Immunohistochemical localization of inhibin subunits in human corpora lutea during menstrual cycle and pregnancy. AB - The cellular localization of the alpha-, beta A-, and beta B-subunits of inhibin was studied in human corpora lutea (CL) during the menstrual cycle and pregnancy. Immunohistochemical techniques using antisera selective for each subunit were used to localize the polypeptide chains. Immunoreactive staining with antisera against the alpha-, beta A-, and beta B-subunits was mainly observed in granulosa luteal cells (luteal cells), whereas thecal luteal cells were faintly stained with antibodies selective for each inhibin subunit. The intensity of immunostaining with alpha-subunit antiserum in luteal cells increased from the early luteal phase to the midluteal phase and subsequently decreased toward the late luteal phase. Inhibin alpha-subunit in the retrogressive CL was not detected. Not only was the immunolocalization of both beta A- and beta B-subunits detected in the luteal cells of the CL of the cycle, but the relative intensity of immunostaining with beta-subunit antiserum changed in a pattern similar to that shown by the alpha-subunit. The luteal cells and thecal luteal cells in the CL of pregnancy exhibited positive staining with antisera directed against each inhibin subunit. The present findings provide further evidence that 1) immunoreactive inhibin subunits are present in luteal cells in the CL of the menstrual cycle; 2) the detectable level of each subunit changes in parallel with the function of the CL over the course of the menstrual cycle; and 3) the CL of pregnancy might be involved in serum inhibin elevation early in gestation. PMID- 1874927 TI - Immunohistochemical detection of parathyroid hormone-related protein in human fetal epithelia. AB - PTH-related protein (PTHrP) is commonly produced by squamous cell carcinomata and is the mediator of the PTH-like features of humoral hypercalcemia of malignancy. It has also been implicated in calcium regulation during fetal development. In this study immunohistochemical techniques, using rabbit polyclonal antibodies to synthetic PTHrP peptides, have been used to localize PTHrP in human fetal tissues from one fetus of 7 weeks and two of approximately 18 and 20 weeks gestation, respectively, in order to identify sites of potential functional significance. PTHrP immunoreactivity was identified in epithelia from many sources, including skin, bronchus, pancreas, pharynx, gut, stomach, and renal pelvis. Thyroid and parathyroid glands, which develop from epithelial origins, also stained positive for PTHrP, as did kidney collecting tubules, adrenal tissue, and skeletal and smooth muscle. PTHrP immunoreactivity was also located in developing long bones and calvaria, where it may have relevance in bone turnover during fetal development. The role of PTHrP at these locations remains to be elucidated, but the identification of specific PTHrP immunoreactivity in fetal epithelia is consistent with PTHrP production by cancers of epithelial origin and supports the hypothesis that PTHrP may have a role in epithelial growth and differentiation. PMID- 1874928 TI - Measurement of individual plasma angiotensins in normal pregnancy and pregnancy induced hypertension. AB - Individual angiotensin peptides were measured by a high pressure liquid chromatography-RIA (HPLC-RIA) technique in the plasma of 20 nonpregnant women, 17 women with normal pregnancy, and 49 with pregnancy-induced hypertension. Immunoreactive angiotensin-II (ANG-II) consisted mainly of ANG-(1-8) octapeptide (greater than 65%), variable proportions (15-25%) of ANG-(4-8) pentapeptide, and small to negligible proportions of ANG-(2-8) heptapeptide and ANG-(3-8) hexapeptide. Levels of ANG-(1-8) were significantly higher in women with normal pregnancy than in both nonpregnant women (P less than 0.0006) and women with pregnancy-induced hypertension (P less than 0.008); in the latter, levels were lower with increasing severity of disease. Levels of ANG-(4-8) were higher in women with normal pregnancy than in women with pregnancy-induced hypertension or nonpregnant women. When expressed as a proportion of ANG-(1-8) levels, however, ANG-(4-8) levels were not higher in normal pregnancy than in women with pregnancy induced hypertension or nonpregnant women. It is concluded that the well known increase in ANG-II levels in normal pregnancy relates predominantly to the active ANG-(1-8) octapeptide and to a far lesser extent to the smaller ANG peptides. Similarly, lower ANG-II levels in pregnancy-induced hypertension relate predominantly to lower ANG-(1-8) levels. PMID- 1874929 TI - Effect of gemfibrozil treatment in sulfonylurea-treated patients with noninsulin dependent diabetes mellitus. AB - This study was initiated to 1) assess gemfibrozil's ability to lower plasma triglyceride (TG) concentration in patients with NIDDM, and 2) determine whether this effect was associated with any changes in glycemic control. Measurements were made of mean hourly plasma glucose, insulin, TG, and FFA concentrations from 1200-1600 h in response to a test meal; hepatic glucose production (HGP); insulin stimulated glucose uptake during a hyperinsulinemic glucose clamp study (MCR); and fasting plasma lipoprotein TG and cholesterol concentrations in 12 patients with NIDDM before and 3 months after gemfibrozil treatment. Although ambient plasma TG and FFA concentrations fell significantly, plasma glucose, insulin, HGP, concentrations fell significantly, plasma glucose, insulin, HGP, and glucose MCR did not change. However, when patients were divided into two groups, those with fasting plasma glucose levels above 9 mmol/L (fair control) and those with levels below 9 mmol/L (good control), a different phenomenon was observed. Patients in fair control had significant decreases in mean hourly plasma concentrations of glucose (15.1 +/- 1.7 to 12.6 +/- 0.9 mmol/L; P less than 0.001), insulin (523 +/- 59 to 471 +/- 75 pmol/L; P less than 0.001), FFA (652 +/ 150 to 504 +/- 76 mumol/L), and HGP (9.5 0.4 to 8.1 +/- 0.4 mumol/kg.min; P less than 0.005), and an increase in glucose MCR (2.63 +/- 0.49 to 3.72 +/- 0.54 mL/kg.min; P less than 0.07) in association with a fall in TG from 6.9 +/- 1.3 to 3.5 +/- 0.9 mmol/L (P less than 0.001). Although fasting low density lipoprotein cholesterol increased (1.8 +/- 0.2 to 2.7 +/- 0.2 mmol/L; P less than 0.05), the ratio of total to high density lipoprotein cholesterol decreased (6.84 +/- 0.88 to 5.80 +/- 1.05; P less than 0.02). Despite a significant fall in mean hourly TG concentration (4.6 +/- 0.7 to 3.8 +/- 0.7 mmol/L; P less than 0.001), neither insulin, FFA, HGP, nor glucose MCR changed in patients in good control. Furthermore, the mean hourly plasma glucose concentration increased from 9.2 +/- 0.7 to 11.7 +/- 1.4 mmol/L (P less than 0.001). Low density lipoprotein cholesterol also increased in this group (1.9 +/- 0.2 to 2.7 +/- 0.2 mmol/L; P less than 0.02), but, as before, the ratio of total to high density lipoprotein cholesterol decreased (8.15 +/- 1.93 to 6.36 +/- 1.03; P less than 0.02). PMID- 1874930 TI - Comparison of intact, midregion, and carboxy terminal assays of parathyroid hormone for the diagnosis of bone disease in hemodialyzed patients. AB - The predictive value of three different RIAs of PTH for the diagnosis of the histological type of bone disease has been compared in 24 asymptomatic patients on chronic hemodialysis who had never been exposed to aluminum intoxication and who agreed to have a bone biopsy after double tetracycline labeling. The serum concentrations of PTH were measured using a two-site immunoradiometric assay for intact PTH(1-84) and region specific assays directed against the C-terminal (53 84) fragment or the midregion (44-68) of the molecule. The bone histomorphometric analysis showed that six patients had nonaluminic adynamic bone disease with low bone formation rate (BFR), eight had mild hyperparathyroidism characterized by increased bone resorption and normal BFR, nine had severe hyperparathyroidism with increased BFR, and only one had true osteomalacia with increased osteoid seam thickness. All PTH assays correlated with the various parameters of bone resorption and bone formation and were able to differentiate the histological type of bone disease only when groups of patients were considered. For classifying individual patients into severe hyperparathyroidism and adynamic bone disease groups, the intact PTH assay had the best predictive value with a sensitivity of 100% and a specificity of at least 70%. A nonaluminic adynamic bone disease was observed in more than 50% of the patients who had normal intact PTH levels (6/11). It is concluded that the intact PTH measurement is superior to C-terminal and midregion assays for the prediction of the histological type of bone disease in hemodialyzed patients and should be of considerable value to adapt their treatment in order to avoid the emergence of both severe hyperparathyroidism and adynamic bone disease. In the absence of aluminum intoxication it seems that maintaining intact PTH concentrations 1 to 1.5 times the upper limit of normal would correspond to the best bone histology. PMID- 1874931 TI - Calcium supplementation reduces vertebral bone loss in perimenopausal women: a controlled trial in 248 women between 46 and 55 years of age. AB - To study the effect of calcium supplementation on perimenopausal bone loss, 295 women were randomized into a control group and 2 supplementation groups receiving, respectively, 1000 and 2000 mg elemental calcium/day for a period of 2 yr. We observed a significant decrease in lumbar bone loss in relation to the calcium supplementation (mean loss after 2 yr of 3.5% in the control group vs. 1.3% and 0.7% in the 1000 and 2000 mg groups, respectively), a significant increase in urinary calcium excretion, and a significant decrease in the urinary hydroxyproline/creatine ratio, serum alkaline phosphatase, osteocalcin, and 1,25 dihydroxyvitamin D. The effect of calcium supplementation on lumbar bone loss was significant in the first year of supplementation, but not in the second. However, the urinary hydroxyproline/creatinine ratio and the serum alkaline phosphatase level remained significantly decreased in the treatment groups at the end of the study; this was not the case for serum osteocalcin. Calcium supplementation did not have a significant effect on metacarpal cortical bone loss. The difference in biochemical parameters between the 2 supplementation groups was small. No significant interaction was observed between the menopausal status of the subjects and the effect of calcium supplementation. We conclude that calcium supplementation retards lumbar bone loss in the first year of calcium supplementation by reducing bone turnover. However, the effect on lumbar bone loss over a longer time span is still uncertain. PMID- 1874932 TI - Hormonal responses during insulin-induced hypoglycemia in manic-depressed, unipolar depressed, and healthy control subjects. AB - Early studies using the insulin tolerance test (ITT) in affective disorders reported a blunted GH response in some depressed patients. However, results from subsequent studies were less consistent. These discrepancies resulted in part from limited sample sizes causing diagnostic heterogeneity. In the present study we examined hormonal response patterns during the ITT in 25 bipolar patients (19 depressed and 6 hypomanic), 91 unipolar depressives, and 51 healthy volunteers to determine whether distinct neuroendocrine response patterns characterized specific diagnostic subgroups. We measured the glucose, GH, PRL, and cortisol responses during a 75-min ITT and observed a diminished cumulative GH response in bipolar hypomanic patients compared to bipolar depressives (P = 0.004) and healthy volunteers (P less than 0.001), and a larger cumulative GH response in bipolar depressives compared to unipolar patients (P = 0.02). No differences were observed in either PRL or cortisol responses among subject groups. The present findings suggest that GH responses during the ITT may be more complex than initially described and partially dependent upon affective disorder subtype. Thus, bipolar patients may have distinctive GH response patterns compared to those of unipolar depressives and healthy controls. Moreover, some of the difference observed in the GH response to the ITT may result from the phase of the manic-depressive illness. These data indicate differences in neuroendocrine substrates between affective disorder subtypes. PMID- 1874933 TI - Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. AB - Maximizing peak bone mass is advocated as a way to prevent osteoporosis. As a prerequisite to the elaboration of any preventive program aimed at maximizing peak bone mass, it is important to determine how the rate of skeletal growth at clinically relevant sites, such as lumbar spine and femoral neck, proceeds in relation to age and pubertal stages in both sexes. Bone mass was assessed in 207 healthy caucasian boys and girls, aged 9-18 yr. Bone mineral density (BMD; grams per cm2) and content (BMC; grams) were determined in lumbar spine (L2-L4), femoral neck (FN), and midfemoral shaft (FS), using dual energy x-ray absorptiometry. Bone variables were correlated with both chronological age and pubertal stage, and compared with young adult (20-35 yr) reference values. The main results are: 1) in males, compared to females, there was a marked age related delay in L2-L4 BMD or BMC increase, but no delay was observed in relation to pubertal stages; 2) at the end of the rapid growth spurt, trends for higher mean values in males were observed for L2-L4 BMC, FN BMD, and particularly FS BMD, but no sex difference was observed for L2-L4 BMD; 3) in females, but not in males, a dramatic reduction in bone mass growth was observed after 15 yr of age, particularly for L2-L4 BMD/BMC and FN BMD. This sharp reduction occurred between the second and fourth years after menarche. In the 14- to 15-yr-old female group, BMD in L2-L4, FN, and FS corresponded to 99.2%, 105.1%, and 94.1%, respectively, and BMC in L2-L4 to 97.6% of the mean values recorded in 20- to 35-yr-old women. In conclusion, this cross-sectional study indicates that during pubertal development, major differences are observed in bone mass growth according to sex and skeletal site. Whereas in males bone mass at different skeletal sites continues to increase substantially between 15-18 yr, skeletal mass growth appears to dramatically slow down at the levels of both lumbar spine and FN at 15 16 yr of age in female adolescents. This suggests that the generally accepted notion that in both males and females bone mass continues to substantially accumulate at all skeletal sites until the fourth decade may not be a constant in human physiology. PMID- 1874934 TI - Insulin effects on glucose and potassium metabolism in vivo: evidence for selective insulin resistance in humans. AB - The effects of insulin on in vivo glucose use and potassium uptake in healthy humans are well documented. However, the interrelationship between these two processes is not fully defined. In order to characterize it, we have used the euglycemic clamp technique on six normal volunteers, two patients with acanthosis nigricans and insulin resistance (AN), and one patient with idiopathic nonazotemic hyperkalemia (HK). In the basal state, all patients had normal fasting blood sugar, the AN patients had fasting hyperinsulinemia (600% of controls), and the HK patient had an elevated plasma potassium level of 5.1 mmol/L (n = 4.2 +/- 0.2 mmol/L). During low dose (1 mU/kg.min), and high dose (10 mU/kg.min) insulin infusions, normals used glucose at a rate of 220 +/- 10 and 470 +/- 20 mg/M2.min, respectively. The HK patient had a normal glucose use at both infusion rates, but the AN patients had a 20% decrease of glucose use compared to normals at the two infusion rates. In normal patients, plasma potassium fell by 0.7 and 1.4 mmol/L at the end of the two infusion periods, respectively. AN patients had a similar fall in potassium, but the HK patient displayed no change in plasma potassium levels during a low dose insulin infusion, and only a 0.6 mmol/L drop during the high dose insulin infusion. These results indicate that: 1) patients with AN are resistant to insulin action on glucose use, 2) AN patients have a normal response to insulin on potassium uptake, 3) HK is a patient with normal response to insulin on glucose use, and 4) this patient is resistant to insulin action on potassium uptake. IN CONCLUSION: 1) we have demonstrated the independence of insulin action on glucose and potassium uptake in vivo, 2) we documented the existence of selective insulin resistance in the above patients, 3) we speculate, that in patients with a normal response to insulin on one parameter of its actions, and subnormal response on another parameter, a postreceptor defect rather than a receptor abnormality must exist. PMID- 1874935 TI - Acanthosis Nigricans, insulin action, and hyperandrogenism: clinical, histological, and biochemical findings. AB - Acanthosis nigricans (AN) is a frequent clinical finding in hyperandrogenic women. Its presence has been used to subgroup such women. We performed this study in order to determine the actual histological prevalence of AN and its relationship to sex hormone levels and insulin action. Insulin-mediated glucose disposal was determined by the euglycemic clamp technique, and neck or axillary skin biopsies were graded blind for the presence and severity of AN in lean and obese women with the polycystic ovary syndrome (PCO) and in age- and weight matched normal ovulatory controls. AN was present on clinical examination in 11 of 13 obese PCO, 3 of 6 lean PCO, 4 of 14 obese normal, and 0 of 4 lean normal women. AN was present on histological examination in 13 of 13 obese PCO, 5 of 6 lean PCO, 13 of 14 obese normal, and 1 of 4 lean normal women. The severity of histological AN was most highly correlated with insulin-mediated glucose disposal (r = -0.61; P less than 0.001) rather than fasting (r = 0.46; P less than 0.05) or glucose-stimulated insulin levels (r = 0.48; P less than 0.01). The only sex steroid correlated with histological AN was dehydroepiandrosterone sulfate (r = 0.46; P less than 0.01). We conclude that 1) clinical skin examination was very insensitive for detecting AN; 2) the best biochemical correlate of histological AN was decreased insulin action, rather than insulin or androgen levels per se; and 3) AN is a very common epiphenomenon of insulin resistance, and its clinical presence should not be used as a criterion for stratifying hyperandrogenic women. PMID- 1874936 TI - The lack of nocturnal serum thyrotropin surge in patients with nontoxic nodular goiter may predict the subsequent occurrence of hyperthyroidism. AB - TSH secretion, with particular regard to the nocturnal TSH surge, was evaluated in 115 subjects with non-toxic nodular goiter. All patients were clinically and biochemically euthyroid. After 18-36 months of follow-up (mean, 24 months), hyperthyroidism occurred in 21 (18%; group 1), while the remaining 94 remained euthyroid (82%; group II). The analysis of hormonal data at the time of first observation showed that the 2 groups had similar total and free T4 and T3 serum concentrations. Morning serum TSH values in group I were lower than those in group II patients (0.6 +/- 0.1 vs. 1.1 +/- 0.1 mU/L; P less than 0.001); this difference was even more striking for the nocturnal values (0.6 +/- 0.1 vs. 2.2 +/- 0.2 mU/L; P less than 0.0001); nocturnal values were significantly lower than morning values in group II, but not in group I. The mean peak TSH value after TRH was also significantly reduced in group I (5.5 +/- 0.4 vs. 9.2 +/- 0.7 mU/L; P less than 0.001). Morning TSH values in group II did not differ from those in controls (1.3 +/- 0.1 mU/L), whereas nocturnal and TRH stimulated peak TSH values were slightly but significantly lower. The nocturnal serum TSH values in control subjects were 62-390% higher than morning values. The nocturnal TSH surge was abolished in 18 of 21 (86%) group I patients and in 7 of 94 (8%) group II patients. TRH testing resulted in an absent or blunted TSH responses in 5 subjects in group I and 6 in group II. Analysis by the Galen and Gambino predictive model; comparing the abolition of the nocturnal TSH surge and the abnormal TRH test as predictors of the subsequent occurrence of hyperthyroidism, showed that the former had higher sensitivity (86% vs. 24%) and predictivity (72% vs. 45%). In conclusion, the results of the present study demonstrate that the evaluation of the nocturnal TSH surge may be useful in identifying patients with nontoxic nodular goiter in whom hyperthyroidism may eventually occur. Patients who lack the nocturnal serum TSH surge are more prone to develop thyroid hyperfunction; their thyroid status should, therefore, be more carefully and frequently monitored. PMID- 1874938 TI - Mechanism of insulin resistance in insulin-dependent diabetes mellitus: a major role for reduced skeletal muscle blood flow. AB - To define the kinetic mechanisms of insulin resistance (IR) in insulin-dependent diabetes (IDDM), we studied seven control (C) and five IDDM (glycohemoglobin, 14 +/- 2+) men matched for age (36 +/- 2 vs. 37 +/- 3 yr), lean body mass (59 +/- 2 vs. 58 +/- 3 kg), and leg volume (mean +/- SEM, 10.4 +/- 0.3 vs. 9.8 +/- 0.5 L). Maximal capacity (Vmax) and affinity (Km) for glucose uptake in whole body (WBGU) and leg skeletal muscle (LGU) were measured during a 120 mU/m2.min insulin infusion, and blood glucose was clamped at about 4, 7, 12, and 21 mmol/L. LGU = femoral arterio-venous glucose difference (FAVGD) X leg blood flow (LBF). Compared to C, IDDMs had about 35% lower rates of WBGU at all glucose levels (P less than 0.01). The FAVGD (millimoles per L) in C vs. IDDM was 1.23 +/- 0.05 vs. 1.06 +/- 0.09, 2.44 +/- 0.11 vs. 2.24 +/- 0.16, 2.91 +/- 0.18 vs. 2.91 +/- 0.30, and 3.27 +/- 0.12 vs. 3.35 +/- 0.4 (P = NS at each glucose). LBF (decaliters per min) was reduced in IDDM vs. C [2.8 +/- 0.5 vs. 4.3 +/- 0.4 (P less than 0.05), 3.1 +/- 0.4 vs. 5.1 +/- 0.7 (P less than 0.05), 2.7 +/- 0.2 vs. 6.3 +/- 0.8 (P less than 0.01), and 3.1 +/- 0.7 vs. 6.5 +/- 0.8 (P less than 0.01) at each glucose level]. Kinetic analysis revealed that 1) the Vmax for WBGU and LGU were reduced in IDDM vs. C (P less than 0.05), and 2) the Vmax for skeletal muscle glucose extraction (FAVGD) was identical in C and IDDM (3.6 mmol/L). The Km values for WBGU, LGU, and glucose extraction were not different in C and IDDM (approximately 6 mmol/L). Thus, in IDDM 1) decreased glucose uptake is due to reduced skeletal muscle glucose uptake; 2) muscle glucose extraction is normal, but blood flow is reduced; and thus, 3) in IDDM, IR is due to reduced glucose and insulin delivery (blood flow) to skeletal muscle. This represents a novel mechanism for in vivo IR. PMID- 1874937 TI - Preservation of pulsatile luteinizing hormone release during postpartum lactational amenorrhea. AB - To evaluate the pulsatile mode of immunoactive LH release during physiological lactational amenorrhea, we withdrew blood samples at 10-min intervals for 24 h from breastfeeding women (n = 9) at both 3 weeks and 3 months postpartum. Nonlactating women (n = 7) were sampled similarly in the early follicular phase of the normal menstrual cycle. Objective LH pulse analysis revealed that the mean frequencies of pulsatile LH release were similar at both times postpartum and in menstruating young women. By 3 months postpartum, mean serum PRL concentrations had declined 50%, and serum LH peak areas doubled. In contrast, LH interpulse interval, peak duration, and maximal, incremental, and fractional LH pulse amplitude did not change significantly. When deconvolution analysis was used to assess pituitary responses to two pulses of exogenous GnRH at 3 months (vs. 3 weeks) postpartum, we found significant increases in maximal LH secretory rates and the total mass of LH secreted. There was no change in the duration or timing of the evoked LH secretory burst and/or the estimated half-life of endogenous LH. In summary, during lactational amenorrhea, pulsatile LH release occurs at a mean frequency no different from that in the normal early follicular phase. As hyperprolactinemia wanes, there is increased pituitary responsiveness to exogenously administered GnRH and a doubling of spontaneous serum LH concentration peak areas. Such amplitude changes are consistent with the hypothesis of increased endogenous GnRH drive (e.g. augmented GnRH secretion per burst and/or increased pituitary responsiveness to available GnRH) during recovery of the postpartum hypothalamopituitary-ovarian axis. PMID- 1874940 TI - The retirement of Professor Robert Edwards. PMID- 1874939 TI - Insulin resistance and hypoglycemia in a patient with systemic lupus erythematosus: description of antiinsulin receptor antibodies that enhance insulin binding and inhibit insulin action. AB - We studied a patient with systemic lupus erythematosus and type B insulin resistance, who progressed from extreme insulin resistance to fasting hypoglycemia. The plasma insulin level was 63.3 +/- 20.9 pmol/L in the fasting state and rose above 1440 pmol/L postprandially. Intravenous administration of human insulin caused almost no decline in plasma glucose. Therefore, it was concluded that the patient was still resistant to insulin and that plasma insulin did not play a crucial role in the development of hypoglycemia. Immunoglobulin G from this patient did not inhibit insulin binding to the insulin receptor; rather, it enhanced [125I]insulin binding in both the immunoprecipitate and the in vitro binding assay to intact cells. Antiinsulin receptor antibodies strongly inhibited insulin internalization in human adipocytes, slowed down the dissociation of [125I]insulin from receptors and failed to induce down-regulation of surface insulin receptors in both the presence and absence of insulin. Finally, autoantibodies mimicked the insulin stimulatory effect on human fat cell lipogenesis even after long term exposure, but inhibited the metabolic potency of insulin when added simultaneously with the natural ligand. We conclude that antiinsulin receptor antibodies induce fasting hypoglycemia, through their continuous receptor stimulatory action, and insulin resistance, possibly by a conformational perturbation of the receptor protein, which, in turn, uncouples insulin receptor binding from receptor function. PMID- 1874941 TI - Bob Edwards--a profile. PMID- 1874942 TI - Fluorescent in-situ hybridization to interphase nuclei of human preimplantation embryos with X and Y chromosome specific probes. AB - Fluorescent in-situ hybridization (ISH) to interphase nuclei of human preimplantation embryos has been demonstrated with the X and Y chromosome specific DNA probes, pBamX7 and pHY2.1, respectively. Assigning the sex on the basis of the number of hybridization signals in the majority of nuclei, the efficiencies with both probes to nuclei from male embryos were considerably higher than those previously reported for pHY2.1 detected by isotopic or conventional non-isotopic methods. Only approximately 15% of nuclei from male embryos failed to hybridize with these probes. With pBamX7, a high incidence (18%) of nuclei with two (or more) signals in embryos classified as males and four signals in a female embryo was observed. In some cases, the double spot nuclei were larger than those with single spots, providing evidence of tetraploidy. The feasibility of using fluorescent ISH for sexing biopsied embryos in couples at risk of X-linked disease and for the preimplantation diagnosis of chromosome abnormalities is discussed. PMID- 1874943 TI - Microsurgical fertilization and teratozoospermia. AB - Semen parameters were correlated with the outcome of partial zona dissection (PZD) in 42 couples with male factor infertility. Although fertilization rates were reduced, 12% of the embryos implanted following replacement. Spermatozoa from teratozoospermic sperm populations were able to fuse with oocytes following zona penetration through the artificial gaps. PZD followed by insemination with less than 5% normal spermatozoa led to 20 embryos which, upon replacement, did not implant. Motility and sperm count were not clearly correlated with the outcome of PZD and are therefore less useful indicators for patient selection. Teratozoospermic patients who previously failed to fertilize were compared to a group of similar patients who had not attempted IVF before. Although fertilization was significantly improved in first-time patients, 41% of the patients whose spermatozoa were initially unable to fertilize had at least one embryo when PZD was performed. Several pregnancies were established in this group. Subzonal sperm insertion (SZI) and PZD were compared in 19 patients using sibling oocytes. A significant fraction of spermatozoa from infertile men were able to fuse with the oolemma when directly inserted into the perivitelline area. Using a sucrose solution to shrink the ooplasm, only 1% of the oocytes were damaged during SZI. Monospermic fertilization rates following PZD and SZI were 15 and 16%, respectively. Both micromanipulation methods were successful in most patients. However, in two small groups of patients, only one technique resulted in fertilization. PMID- 1874944 TI - Presentation of six pregnancies established by sub-zonal insemination (SUZI). AB - Clinical trials were undertaken to evaluate sub-zonal insemination (SUZI) for the procurement of fertilization in infertile couples. We present here the six pregnancies resulting from this work. Insemination of multiple sperm was used, with a mean of 3.7 +/- 2.1 (SD) per oocyte. One hundred and thirty patients presented either with previous failures of fertilization in vitro and/or with severe seminal defects, including oligo-, astheno-, oligo-astheno- or necro zoospermia. Forty-one (31.5%) patients achieved fertilization and 39 had replacement of conceptuses. Six patients achieved a pregnancy (4.6% overall, 15.4% per replacement), four have delivered and two have miscarried. The implantation rate was nine conceptuses from a total of 61 replaced (14.8%); and of the six women who conceived, nine of 11 replaced conceptuses implanted. Of the oocytes recovered, 539 were used for SUZI, of which 69 (12.8%) fertilized. Three singleton pregnancies resulted, two from patients having one conceptus replaced, the other from the replacement of three conceptuses. Two twin pregnancies were produced, both in patients having two conceptuses replaced. The sixth pregnancy, a triplet, occurred in a patient having three conceptuses replaced, one conceived after standard in-vitro fertilization (IVF), the other two after SUZI. Two sets of non-identical twins, both one male and one female, a singleton female and female (non-identical) triplets have been born, normal and healthy. PMID- 1874945 TI - Human preimplantation embryo cryopreservation: selected aspects. AB - This report describes the results of cryopreserving human preimplantation zygotes and cleaved embryos (2-4 cells) in our in-vitro fertilization programme. Cryopreserved zygotes and cleaved embryos resulted in similar post-thaw survival rates (74.8 versus 70.9%). Pregnancy rates per retrieval cycle (RC) and embryos transferred per pregnancy for frozen-thawed zygotes versus frozen-thawed cleaved embryos were 21.8 versus 11.5% (P less than 0.2) and 12.6 versus 17.5 (P less than 0.2), respectively. Pregnancy rates increased significantly for both fresh (P less than 0.0005) and frozen-thawed (P less than 0.05) embryos as the number of embryos replaced per transfer increased from one to three or more. Frozen thawed embryos resulted in multiple implantation rates per transfer of 25 compared to 6.4% (P less than 0.1) for fresh embryos when two embryos were replaced. Pregnancy rates were reduced for fresh (P less than 0.05) and frozen thawed (P less than 0.1) embryos obtained from patient retrieval cycle numbers greater than 3. The method of follicular stimulation during the retrieval cycle did not affect frozen-thawed embryo survival rates. There was no difference in pregnancy rates from frozen-thawed embryos replaced during natural or clomiphene citrate transfer cycles. Patients with cryopreserved embryos had cumulative pregnancy rates of 37.1% (66/178) compared to 23.5% (110/468) (P less than 0.01) for patients with no embryos cryopreserved; cryopreservation of preimplantation embryos is a reliable therapeutic procedure that enhances achievement of pregnancy through in-vitro fertilization. PMID- 1874946 TI - The influence of in-vitro development upon post-thaw survival and implantation of cryopreserved human blastocysts. AB - Blastocysts from 198 patients were frozen using glycerol as cryoprotectant. No difference in the post-thaw survival of blastocysts or implantation rates was found between 177 patients (122 transfers) with all surplus embryos cultured to blastocysts before freezing and 20 patients (12 transfers) whose embryos were considered unsuitable for freezing during cleavage and were then frozen as blastocysts. Nineteen pregnancies were achieved, of which six aborted. Pre freezing morphology was similar in blastocysts of patients in groups 1 and 2 and did not relate to their survival after cryopreservation. A significantly lower proportion with suspected damage after thawing was present among patients becoming pregnant after transfers of single blastocysts (P less than 0.01) and implanting embryos were in general more expanded at the time of transfer. No differences were detected between blastocysts resulting in normal development and those leading to abortion. The developmental consequences of damage to human blastocysts are discussed. PMID- 1874947 TI - Cryoprotection of human oocytes: inappropriate exposure to DMSO reduces fertilization rates. AB - Human oocytes were exposed to the cryoprotectant dimethyl-sulphoxide (DMSO) at either 4 or 37 degrees C. Subsequent fertilization of these oocytes showed that exposure to DMSO at 37 degrees C was associated with a greatly reduced fertilization rate when compared to untreated control oocytes, whereas no such reduction was seen in oocytes exposed to DMSO at 4 degrees C. The significance of these results for the potential cryopreservation of human oocytes is discussed. PMID- 1874948 TI - Whole embryo culture and teratogenesis. AB - Whole embryo culture (WEC) is under evaluation in numerous laboratories to determine the role it should play in teratogen testing. There is general agreement that its role is to complement the Segment II Teratology studies required by regulatory authorities. Currently it is used as a 'screen' in order to minimize the number of compounds used in animal tests and also to determine the mechanism(s) of teratogenesis. This brief review focuses on the study of retinoid teratogenicity in WEC in order to illustrate these points. PMID- 1874949 TI - Vitamin deficiencies and neural-tube defects: human and animal studies. AB - The evidence for an association between vitamin deficiency in early pregnancy and the prevalence of neural-tube defects in humans is reviewed, with particular emphasis on the methodological problems encountered in conducting such studies. It is apparent that there is strong evidence for an association between maternal vitamin status and the outcome of pregnancy, but this is not universally accepted, due to ethical and practical constraints on the design of the studies. There are also problems in obtaining precise information from experiments on animals in vivo. By culturing rat embryos in dialysed serum in which the micromolecular component is defined, it has been possible to demonstrate that significant numbers of neural-tube defects can be produced by the deficiency of a single vitamin (inositol), and that multiple vitamin deficiency produces a further significant increase in the frequency of such defects. PMID- 1874950 TI - Effect of stevioside on growth and reproduction. AB - The effect on growth and reproduction in hamsters of stevioside, which is extracted from stevia leaves (Stevia rebaudiana Bertoni) and is currently used as a non-caloric sweetener, was investigated. Four groups of 20 one-month-old hamsters (10 males and 10 females) were daily force-fed with stevioside (0.0, 0.5, 1.0 and 2.5 g/kg body wt/day, respectively). No abnormalities were found in growth and fertility in both sexes. All males mated females efficiently and successfully. Females showed normal 4-day oestrus cycles and became pregnant after mating. Each female was mated and allowed to bear three litters during the period of experiment. The duration of pregnancy, number of fetuses, as well as number of young delivered each time from females in the experimental groups were not significantly different from those in the control group. The young F1 and F2 hamsters continuously receiving stevioside via drinking water until one month old and daily force-fed afterwards at the same doses as their parents showed normal growth and fertility. Histological examinations of reproductive tissues from all three generations revealed no evidence of abnormality which could be linked to the effects of consuming stevioside. We conclude that stevioside at a dose as high as 2.5 g/kg body wt/day affects neither growth nor reproduction in hamsters. PMID- 1874951 TI - The WHO Task Force on Vaccines for Fertility Regulation. Its formation, objectives and research activities. AB - Over the past 18 years, the WHO Task Force on Vaccines for Fertility Regulation has been supporting basic and clinical research on the development of birth control vaccines directed against the gametes or the preimplantation embryo. These studies have involved the use of advanced procedures in peptide chemistry, hybridoma technology and molecular genetics as well as the evaluation of a number of novel approaches in general vaccinology. As a result of this international, collaborative effort, a prototype anti-HCG vaccine is now undergoing clinical testing, raising the prospect that a totally new family planning method may be available before the end of the current decade. PMID- 1874952 TI - The incidence of abnormal morphology and nucleocytoplasmic ratios in 2-, 3- and 5 day human pre-embryos. AB - Human cleaving pre-embryos at 2 and 3 days and cavitated pre-embryos at 5 days post-insemination have been examined for cell number and the incidence of mononucleated cells. At least 60% of polynucleate or anucleate cells have been detected at all these stages and regardless of morphological grading at day 2. It is concluded that even by the time at which pre-embryo replacement would occur therapeutically, the majority of pre-embryos are unlikely to have full developmental potential. The possible origins of the abnormalities of nucleocytoplasmic ratios are discussed. PMID- 1874953 TI - An investigation of the fate of cells transplanted orthotopically between morulae/nascent blastocysts in the mouse. AB - A technique has been devised for selectively replacing some inside cells (ICs) or outside cells (OCs) of late morulae/nascent blastocysts with corresponding cells from genetically dissimilar, synchronous embryos. The main purpose was to determine whether the inner cell mass (ICM) contributes cells to the overlying polar trophectoderm at any stage during the blastocyst phase of development. Notwithstanding the high incidence and level of chimaerism in ICM derivatives of post-implantation conceptuses obtained in the IC transplantation experiments, trophoblast tissue was composed entirely of host cells in the majority of cases. Even where a donor IC contribution to trophoblast was detected there were strong grounds for suspecting that it was due to tissue contamination rather than genuine chimaerism. Thus, not only did such contributions differ in both level and distribution from those produced by transplantation of OCs but they also varied markedly in frequency according to the day of gestation on which conceptuses were dissected. The possibility that ICs regularly colonize the polar trophectoderm but fail to persist there was excluded by the results of short-term transplantation experiments using an in-situ genetic marker. These findings offer no support for the hypothesis that the ICM serves as a population of stem cells for the trophectoderm as well as the primitive endoderm and ectoderm during normal development. The frequency of chimaerism was lower in OC than IC transplantation experiments. Nevertheless, in a substantial proportion of chimaeras, OCs colonized derivatives of the ICM. This is consistent with evidence from other studies that some outside cells divide differentially at 5th cleavage to produce an OC plus an IC rather than two OCs. PMID- 1874954 TI - Postnatal compensatory growth of manipulated mouse embryos. AB - As an extension of the biometrical analysis of data described in an earlier paper (Papaioannou et al., 1989, Development, 106, 817-827), we have examined the extent of postnatal compensatory growth in body weight and tail length of genetically identical F1 mice from the following groups: controls--the natural offspring of timed matings; transferred controls--offspring from embryos flushed at the 2-cell stage and transferred to recipient foster mothers; and transferred half embryos--offspring developing from one blastomere from the 2-cell stage transferred to recipient foster mothers. There was little difference between the postnatal growth curves of transferred controls and mice produced from half embryos, indicating regulation during prenatal development is complete and that halving an embryo at the beginning of gestation has no lasting effects on its size or postnatal growth rate. In contrast, embryo transfer itself had a significant effect, resulting in smaller litters and larger, more variable animals after birth. There was then a period of postnatal compensatory growth in body weight and tail length after 4 weeks of age. We have provided direct evidence that animals that become relatively large during early growth curtail their growth rate compared to small animals as they approach maximum size and the reverse occurs with small animals. A similar phenomenon was observed for tail length. Although the overall variance of embryo transfer mice is high during postnatal growth, the intraclass correlation coefficient is also high, making them useful for comparative experiments. PMID- 1874955 TI - Influence of genome imprinting on gene expression, phenotypic variations and development. AB - Genome imprinting confers functional differences on parental chromosomes as a result of the differences in epigenetic inheritance from parental germlines. Repressed and derepressed chromatin structures probably constitute the initial germline-dependent 'imprints'. Any subsequent modifications, such as DNA methylation, will be influenced by these initial epigenetic modifications. Hence, epigenetic modifications of parental alleles probably occur progressively and this will affect their potential for expression. It appears that imprinting of some parental alleles is critical for their dosage, affecting embryonic growth, cell proliferation and differentiation. Genetic studies highlight the influence of subsets of imprinted genes and identify those which are crucial for development. Genomic imprinting also affects some transgene loci and dominant mutations with accompanying variable penetrance and expressivity. The response of transgenes can be influenced by modifier genes whose presence is most readily detected in different inbred backgrounds. The influence of modifier genes can in turn be affected by their parental origin, perhaps partly by the maternally inherited oocyte cytoplasmic factors, as well as by complex interactions between some parental alleles and oocyte cytoplasmic factors. The resulting epigenetic modifications of unlinked loci can result in substantial phenotypic variations. PMID- 1874956 TI - In the beginning there was Bob. PMID- 1874957 TI - An investigation by mathematical modelling of whether mouse and human preimplantation embryos in static culture can satisfy their demands for oxygen by diffusion. AB - Mammalian preimplantation embryos are conventionally grown in small, static droplets of medium. By contrast, embryos within the oviduct are subject to mixing forces arising from the action of cilia and the contractions of the myosalpinx. Such forces will minimize the buildup of unstirred layers around the embryos and facilitate the exchange of gases and metabolites. We have devised a mathematical model to investigate whether preimplantation mouse and human embryos grown in static culture can satisfy their requirement for oxygen solely by diffusion i.e. in the absence of stirring. The model incorporates the diffusion coefficients for oxygen in the medium outside and within the embryo, the oxygen tension of the culture medium, the size of the embryo and its oxygen uptake. Solutions of the model are provided for mouse oocytes and 2-cell embryos, mouse blastocysts and human morulae. In each case, the model is solved for two different values of the diffusion coefficient of oxygen within the cell and of the oxygen content of the medium (5 and 20%). The conclusion is that mouse embryos in static culture are likely to be able to satisfy their demands for oxygen by diffusion alone, but that human embryos may become marginally hypoxic, especially at lower oxygen levels. PMID- 1874958 TI - The culture of postimplantation embryos. AB - Culture methods for postimplantation embryos are now widely used in studies of embryo physiology, growth and development. Available methods support growth and development of rat and mouse embryos at all stages of organogenesis. The best results are obtained from embryos between head fold and early limb bud stages; overall growth and differentiation of these embryos in vitro is almost identical to that in vivo. Some examples of the application of postimplantation embryo culture to specific lines of study are given and some possible future developments of the technique are discussed. PMID- 1874960 TI - The intra-vaginal culture technique for supernumerary oocytes from gamete intra Fallopian transfer. AB - The intra-vaginal culture technique has been utilized for supernumerary oocytes produced as a result of gamete intra-Fallopian transfer therapy. This has enabled knowledge regarding fertilization to be gained and in addition, by adapting the technique to include a transportational element, it has been possible to perform embryo cryopreservation in a separate unit. Analysis of the results of 72 GIFT treatment cycles reveals that when more than four oocytes were collected at laparoscopy, 15/32 (47%) pregnancies were achieved, in comparison with 7/40 pregnancies (17.5%) when four or fewer oocytes were recovered (P less than 0.01). Whilst the GIFT pregnancy rate was higher when spare oocytes were fertilized and embryos cryopreserved (9/16; 56%), six of the 16 patients (37.5%) with failed fertilization of spare oocytes still achieved a GIFT pregnancy. PMID- 1874959 TI - Energy substrate requirements for in-vitro development of hamster 1- and 2-cell embryos to the blastocyst stage. AB - Energy substrate requirements (pyruvate, lactate and amino acids) were determined for in-vitro development of hamster 1- and 2-cell embryos to blastocysts, using a chemically defined, protein free medium (hamster embryo culture medium, HECM). One-cell embryos were very sensitive to energy substrate type and concentration. Pyruvate alone could not support development of 1-cell embryos to greater than 4 cells, whereas lactate as sole energy substrate supported 14% development into morulae/blastocysts. Pyruvate, with lactate and 20 amino acids, inhibited 1-cell embryo development into blastocysts relative to lactate and 20 amino acids. The highest development of 1-cell embryos to blastocysts (up to 27%) occurred with reduced lactate concentration (less than 10 mM) and either 20 amino acids or 0.2 mM glutamine. Hamster 2-cell embryos were much less sensitive to energy substrates, requiring only lactate for development to blastocysts (53%). Lactate with 20 amino acids supported 70-75% of 2-cell embryos to blastocysts. Glutamine as sole energy and nitrogen source supported development to morulae and blastocysts of some 2-cell, but not 1-cell, embryos. Pyruvate did not enhance development of 2-cell embryos. We conclude that (i) altering the types and concentrations of available energy substrates drastically changes the developmental responses of 1-cell hamster embryos in vitro and (ii) energy substrate requirements for hamster embryo development in vitro are markedly different from those of mouse embryos, the standard model for studies on preimplantation development. This is the first report of successful in-vitro culture of hamster 1-cell embryos to the blastocyst stage. PMID- 1874961 TI - New insights into triploidy and tetraploidy, from an analysis of model systems for these conditions. AB - While triploids and tetraploids together probably account for approximately 20% of all spontaneous abortions with a numerical chromosomal defect, and consequently give rise to a significant proportion of human pregnancy wastage, relatively little is known about their early embryogenesis and phenotypic features. We have therefore studied the early post-implantation stages of development of spontaneously occurring digynic triploid mouse embryos and experimentally induced diandric and digynic triploids, as well as diandric heterozygous diploids and homozygous tetraploid embryos. This material has been examined morphologically and cytogenetically, in order to investigate whether any relationship exists between their phenotype, genotype and developmental potential. Attention is drawn to the fact that the detailed analysis of this material has already shed important new light on the genetic factors that influence early mammalian development. In addition, it appears likely that it has the potential to provide new insights into pattern formation, in particular in relation to the craniofacial region, the heart and the post-cranial vertebral axis. PMID- 1874962 TI - In-vitro studies on 'spare' human preimplantation embryos in culture. AB - Methods previously used for the biopsy of preimplantation mouse embryos have been applied to individual 'spare' human embryos. Early cleavage-stage human embryos have been cultured and individual blastomeres removed following zonae thinning or drilling. Embryos have also been cultured to the blastocyst stage for the biopsy of three to five trophectoderm cells. Both the biopsied embryo and the biopsied cells have been allowed to develop and/or grow in vitro. PMID- 1874963 TI - Calponin and the composition of smooth muscle thin filaments. PMID- 1874964 TI - Visualization of myosin exchange between synthetic thick filaments. AB - Exchange of myosin molecules between synthetic thick filaments was examined by fluorescence energy transfer and visualized by electron microscopy using streptavidin-gold to detect exchanged biotinylated myosin molecules. N hydroxysuccinimido-biotin (NHS-biotin) was covalently linked to purified adult chicken pectoralis myosin to obtain assembly-competent biotinylated myosin molecules. Two distinct classes of synthetic filaments, distinguishable by length, were prepared. Biotinylated filaments (575 +/- 100 nm) were assembled by a quick dilution (QD) method and unlabelled filaments (1025 +/- 250 nm) were obtained by a sequential dilution (SD). The two filament population maintained their distinct length distributions even when mixed. To measure exchange, biotinylated short (QD) filaments were combined with unlabelled long (SD) filaments at a 1:5 ratio, sampled at varying times and the entry of biotinylated myosin into the previously unlabelled long filaments visualized by the addition of streptavidin-gold. The number of gold particles per micron was examined for fully biotinylated short filaments (less than 700 nm), unlabelled long filaments (greater than 900 nm), and exchanged filaments. Equivalent binding of streptavidin-gold to the two filament types was detected by 60 min suggesting randomization of biotinylated monomers by this time. The precise location of streptavidin-gold sites on the long filaments was also measured. Although labeling was detected along the full length of the filaments, at the earliest time points (5 min) filament ends contained twice the number of gold particles as the filament centers. Approximately equivalent labeling along the entire length of the filaments was observed by 60 min. These results provide additional support for our earlier report of extensive myosin exchange between synthetic thick filaments and show that extensive exchange takes place rapidly along the full length of synthetic thick filaments. PMID- 1874965 TI - X-ray diffraction study of the structural changes accompanying phosphorylation of tarantula muscle. AB - Electron microscopy of negatively stained isolated thick filaments of tarantula muscle has revealed that phosphorylation of myosin regulatory light chains is accompanied by a loss of the helical order of myosin heads. From equatorial X-ray diffraction patterns of tarantula muscles in the phosphorylated state we have detected a mass movement in the myosin filaments that supports this finding. PMID- 1874966 TI - Changes in sarcoplasmic metabolite concentrations and pH associated with the catch contraction and relaxation of the anterior byssus retractor muscle of Mytilus edulis measured by phosphorus-31 nuclear magnetic resonance. AB - The sarcoplasmic concentrations of phosphorus metabolites and pH (pHin) were measured in the anterior byssus retractor muscle (ABRM) of Mytilus edulis by 31P nuclear magnetic resonance spectroscopy. During an active contraction induced by 10(-3) acetylcholine, the concentration of arginine phosphate ([Arg-P]in) decreased from the resting value of 7.47 +/- 0.26 (mean +/- SE, n = 8) to 6.67 +/ 0.29 (n = 6) mumol g-1, and that of inorganic phosphate (Pi) consistently increased from 0.84 +/- 0.06 (n = 7) to 1.61 +/- 0.12 (n = 5) mumol g-1. In the 'catch' state following the active contraction, these concentrations were close to their resting levels, indicating that the catch is an inactive state. 5 hydroxytryptamine caused a rapid relaxation of the catch, which was associated with a slight decrease in [Arg-P]in and an increase in pHin by ca 0.2 units. The sarcoplasmic concentration of ATP (mean, 1.6 mumol g-1) did not change throughout the contraction-relaxation cycle. PMID- 1874967 TI - Expression of slow and fast myosin heavy chains in overload muscles of the developing rat. AB - The present study examines the developmental accumulation of slow myosin heavy chain in the extensor digitorum longus, soleus and plantaris muscles of rats after early post-natal imposition of mechanical overload by removal of synergistic muscles. The proportions of slow and fast myosin heavy chain were measured in each muscle by ELISA. Fibres expressing slow myosin were examined immunocytochemically using a monoclonal antibody specific for slow MHC. Between 30 and 60 days of age, MHC increases by 15% (p less than 0.001) in the soleus and by 27% (p less than 0.001) in the plantaris of normally developing, unoperated animals. The effect of overload on the soleus and plantaris is to accelerate the rate of increase in slow MHC accumulation so that levels are respectively 16 and 39% higher than controls by 30 days of age (p less than 0.001). By 60 days, the control soleus and plantaris attain levels of slow MHC roughly equivalent to their overloaded counterparts. In overloaded plantaris the increase in levels of slow myosin does not occur at the expense of fast myosin expression. In the EDL there is a normal developmentally regulated decrease in slow MHC accumulation, reflected by a 40% decrease in levels of slow MHC (p less than 0.0001) and a 50% decrease in the number of slow fibres (p less than 0.001), between 30 days and 20 weeks of age. This elimination of slow myosin accumulation in the EDL is unimpeded by chronic overload. Thus, muscles react to mechanical overload in a tissue specific manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1874968 TI - Identification of and pattern of transitions of cardiac, adult slow and slow skeletal muscle-like embryonic isoforms of troponin T in developing rat and human skeletal muscles. AB - Using a monoclonal antibody (CDC4) that recognizes both the cardiac and slow skeletal isoforms of troponin T in an immunoblotting procedure, the composition of troponin T isoforms in adult and developing skeletal muscles of the rat and human were studied. Two major isoforms of slow troponin T (HS1 and HS2) were detected in all the adult human skeletal muscles investigated. Significant amounts of another isoform (HS3) in addition to HS1 and HS2 were also detectable in a subgroup of these muscles. All the human fetal skeletal muscles at 20 weeks of gestation expressed HS1 and HS2 isoforms but not HS3. The fetal skeletal muscles, also expressed cardiac troponin T in addition. Unlike the human skeletal muscles, only a single isoform of slow troponin T was detected by antibody CDC4 in both the adult and neonatal rat skeletal muscles. The investigation of fetal rat skeletal muscles using the same antibody, however, detected the presence of not only the embryonic cardiac and adult slow skeletal isoforms but also five additional not previously described isoforms (Es1-Es5) of troponin T. These embryonic isoforms, Es1-Es5, were undetectable in the postnatal skeletal muscles although their small amounts could be detected in the neonatal rat hearts. The analysis of individual skeletal muscles from different parts of the body at different stages of fetal development showed marked variations in both the composition of troponin T isoforms and the time sequence of their transitions in each muscle. PMID- 1874969 TI - A comparison of fibrillation in denervated skeletal muscle of the anaesthetized rat and guinea-pig. AB - We have used intracellular recording in vivo to study fibrillation (spontaneous repetitive membrane activity) in extensor digitorum longus (fast twitch) and soleus (slow twitch) muscles of the anaesthetized rat and guinea-pig denervated for periods of about 10 to 60 days. The proportion of fibres fibrillating in the guinea-pig soleus was greater than 50% in most animals up to the longest period of denervation (65 days). Fibrillation was rarely found in rat soleus after three weeks of denervation. Its incidence in the extensor digitorum longus muscles of both species was intermediate. The mean frequency of fibrillation was higher in guinea-pig extensor digitorum longus (16 Hz) and soleus (8 Hz) than in the rat extensor digitorum longus (3 Hz) and soleus (2 Hz). The resting membrane potentials of the denervated muscles were less than normal and correlated inversely with the frequency of fibrillation but not with the incidence of fibrillation: in rat soleus, many fewer fibers were fibrillating at a given membrane potential than in the other three muscles. The incidence of fibrillation was compared with previously reported tensions of the four denervated muscles and was found to have the same rank order. We suggest that fibrillation may reduce atrophy (and hence tension loss) of denervated muscle, which may have implications for artificial stimulation. Fibrillation frequency was directly related to changes in twitch speed of the four muscles after denervation. PMID- 1874970 TI - Developmental myosin heavy chain progression in avian type IIB muscle fibres. AB - Myosin heavy chain species were investigated during development in avian pectoralis major muscles (type IIB fibres) by high resolution anion-exchange chromatography of the myosin head region, subfragment-1. At 15 days in ovo four distinct fast-type heavy chain species, I, II, III and IV, in order of elution, were identified. By 19 days in ovo, form IV had become predominant and remained the major species through 3-days post-hatch. This form has been named the peri hatch form. Between 3 and 5 days post-hatch, a second massive change occurred such that by 5 days post-hatch a new species, V, apparent at 19 days in ovo in small amounts, dominated and at 8 days post-hatch was the only heavy chain species present. Form V, which corresponds to that previously identified as the post-hatch form, continued as the major species through 20 days post-hatch and was replaced slowly by the adult form. N-terminal sequencing of CNBr peptides from three subfragment-1 heavy chain species, the peri-hatch (form IV), the post hatch (form V) and adult, revealed differences in amino acid sequence consistent with the three being products of different genes. These results confirm and extend recent reports of complexity in fast heavy chain expression prior to hatching in the chicken (Hofmann et al., 1988; Van Horn & Crow, 1989). PMID- 1874971 TI - The annual meeting on Muscle Contraction and Cell Motility in Japan, January, 1991. PMID- 1874972 TI - Abstracts of the 1990 annual meeting on muscle and cell motility physiology. Tokyo, 29-30 October 1990. PMID- 1874973 TI - Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdialysis: evidence of a role for microglia in cytokine production. AB - In vivo levels of interleukin-1 (IL-1) and IL-6, present in the interstitial spaces of brain, have been repeatedly monitored up to 7 days after insertion of a microdialysis probe, designed to induce mechanical trauma to the brain. IL-1 is barely detectable immediately after implantation but over a 24-48 h period a 15 fold increase is seen. In contrast IL-6 levels at day 0 are high, increasing slightly (10%) by day 1 but decreasing to 40% by day 2. The temporal pattern of IL-6 recovery in the cerebrospinal fluid was similar to that in the dialysate but the levels were significantly lower and may reflect diffusion from the site of the probe lesion. Cellular sources of these cytokines include macrophages and neutrophils, which have infiltrated the lesion and microglia resident in the brain, which can be identified at the lesion site within 24 h of probe implantation. The astrocytic response to injury, evidenced by increased glial fibrillary acidic protein staining occurs much later, by day 7, and is unlikely to be responsible for IL-1 and IL-6 production found at 24-48 h. Since upon isolation and stimulation of microglia in vitro with lipopolysaccharide IL-1 and IL-6 can be measured in the supernatant, it would appear that they have the capacity to produce cytokines in vivo. Localised synthesis of cytokines at sites of brain injury by microglia would further stimulate microglia in an autocrine manner and also propagate the astrocytic reaction. PMID- 1874974 TI - Appearance of cytokine-associated central nervous system myelin damage coincides temporally with serum tumor necrosis factor induction after recombinant interleukin-2 infusion in rats. AB - Endogenous tumor necrosis factor (TNF) activity, assessed by L-929 fibroblast bioassay, was determined in serum samples from rats infused intravenously with recombinant interleukin-2 (rIL-2) or rIL-2 vehicle. Parallel studies of cerebral ultrastructure were conducted in additional rats, comparably infused. Rats received rIL-2 or vehicle either one time only or 3 times daily for 3 days. TNF activity was assessed at 2, 4, and 8 h after the single or final infusion. Rats employed for ultrastructural studies were sacrificed at 4 h after the single or final infusion. Every rIL-2-infused rat exhibited unusual abnormalities of axonal ultrastructure, identical to those previously described after in vitro TNF application to living spinal cord slices. Serum samples drawn during and after the development of axonal changes revealed significantly elevated circulating TNF activity. Controls exhibited neither TNF activity nor altered axons. These studies demonstrate that, following rIL-2 infusion in rats, endogenous TNF circulates at elevated levels during the development of rIL-2-related central nervous system abnormalities similar to those produced in vitro by recombinant TNF. Whether rIL-2-induced circulating TNF is causally-related to the observed myelin damage remains to be determined but merits further investigation, particularly since blood-brain barrier function has been shown to be compromised following rIL-2 infusion. PMID- 1874975 TI - Modulation of natural killer cell-mediated lysis by corticotropin-releasing neurohormone. AB - Existence of a reciprocal neuroendocrine-immune relationship led us to study an immunomodulatory role for the corticotropin-releasing factor (CRF) which is a low molecular weight peptide neurohormone of the neuroendocrine system. In the present study, the CRF-induced modulation of natural killer (NK) cell-mediated lysis (CML) was investigated. The pretreatment for 16-18 h of human peripheral blood mononuclear cells (MNC) with CRF in nanomolar concentrations caused a statistically significant increase in the CML function of NK cells as measured against K562 target cells in the 4-h 51Cr-release assay. The maximum stimulation occurred at a final concentration of 1 nM CRF despite some variability from one blood donor to another. The depletion of monocytes from MNC abolished the stimulatory effect of CRF but the effect was reconstituted by the supplementation of monocyte-derived interleukin-1 (IL-1), suggesting the involvement of IL-1 in the stimulation of NK cell-mediated lysis. Additionally, the CRF-induced stimulatory effect was inhibited by specific antibodies to IL-1 (anti-IL-1) or beta-endorphin (anti-beta E), indirectly suggesting that IL-1 and beta E may act as the mediators of stimulation by CRF of NK cell function. Based on these in vitro studies, we hypothesize that the CRF modulates NK cell-mediated lysis via initial stimulation of monocytes to produce IL-1 triggering the release by B cells of beta E for the stimulation of NK cell function. PMID- 1874976 TI - Arrestin mRNA expression, biosynthesis, and localization in degenerating photoreceptors of mutant rds mice retinas. AB - The retinal photoreceptors of the mutant rds mouse are unable to form normal outer segments. Eventually the abnormal cells die in the months following birth. The genetic defect in the rds mouse was recently localized to the peripherin gene that encodes a protein in the outer segment disc margin. Although this mutation may explain the morphogenetic defect, i.e., the failure to form outer segments, the reason for subsequent cell death is not clear. Previously, we demonstrated that the capability to synthesize opsin, an outer segment integral membrane protein, is not compromised by the morphogenetic defect although the opsin steady state content is considerably reduced, since it is not incorporated into an organized outer segment. We have now studied arrestin, a cytoplasmic protein that is part of the phototransduction cascade and appears to shuttle between the inner and outer segment during the light/dark cycle. Since rds mice lack outer segments, it was of interest to determine the effects of the photoreceptor abnormality on arrestin gene expression. Arrestin mRNA levels and protein synthetic rates were high in young rds retinas. When corrected for cell loss, the steady-state arrestin content per cell in the rds retina was comparable to normal. However, in the absence of an outer segment, the total amount of arrestin is concentrated in the remaining inner segment. Consequently, a relatively high level of arrestin is present in the rds inner segment throughout the light/dark cycle. We suggest that the morphogenetic defect indirectly precipitates secondary effects such as the persistent presence of high levels of arrestin or other soluble proteins in the abnormal photoreceptor inner segment, nucleus, and synaptic terminal. This condition, if toxic to the cells, may compromise photoreceptor viability in the rds retina. PMID- 1874977 TI - GABA and enkephalin in the lateral septum of the guinea pig: light and electron microscopic evidence for interrelations. AB - Tract tracing techniques combined with immunohistochemistry in rats and guinea pigs have demonstrated the existence of a hypothalamo-lateral septum enkephalinergic pathway. Numerous enkephalinergic nerve endings encompass cell bodies located in the lateral septum. The present immunocytochemical study, at light and electron microscopic levels, was undertaken in the guinea pig brain to determine whether the contacted perikarya contain gamma-aminobutyric acid (GABA). The antisera against GABA revealed the presence of immunoreactive cell bodies throughout the lateral septum. At the light microscopic level, most GABA neurons appeared round while others were oval with one or two emerging dendrites. Ultrastructurally, cell bodies displayed a moderate number of organelles and a pale nucleus with frequent indentations of the nuclear envelope. The precise relationship between GABA neurons and enkephalinergic terminals was examined by means of a double-immunostaining method showing that 60% of cell bodies receiving synaptic inputs from enkephalinergic afferents contained GABA. These results show that the hypothalamo-septal enkephalinergic pathway prominently innervates GABA containing neurons and also provide anatomical basis suggesting a disinhibitory role for this enkephalinergic tract. PMID- 1874978 TI - Androgenic regulation of dendritic trees of motoneurons in the spinal nucleus of the bulbocavernosus: reconstruction after intracellular iontophoresis of horseradish peroxidase. AB - Androgen-sensitive motoneurons in the spinal nucleus of the bulbocavernosus (SNB) in adult male rats were labeled after intracellular iontophoresis of horseradish peroxidase, after which they were fully reconstructed in three dimensions in order to measure their dendritic trees. Three groups of rats were compared: intact adult male rats and male rats castrated as adults and given Silastic tube implants containing either testosterone or nothing. In the high-androgen groups (intact males and testosterone-treated castrates), soma size and the diameter of the first-order dendrites were larger than in blank-treated castrates. Moreover, the terminal dendrites in all groups possessed growth cones, implying that the dendrites of these motoneurons are capable of growth in adulthood. However, there were no statistically significant group differences in the length, membrane surface area, or volume of the dendritic trees, or in the orientation or branching symmetry of dendrites. In general, there were positive correlations between the size of the motoneuronal soma and various measures of the size of the dendritic tree and between the diameter of individual stem (first-order) dendritic branches and the size of remainder of that dendrite. These data suggest that there may be a modest effect of androgen on the size of the dendritic trees of SNB motoneurons in adulthood, although the effect is much smaller than has previously been reported. PMID- 1874979 TI - Morphogenesis of adrenergic cells in a frog parasympathetic ganglion. AB - The development of the parasympathetic cardiac ganglion of the frog Xenopus laevis was marked by the differentiation of a population of adrenergic small intensely fluorescent (SIF) cells. The neural crest contributes precursors for both SIF cells and the well-studied cholinergic cardiac ganglion neurons; this situation provided an opportunity to determine whether morphogenesis of the two cell types was correlated. Accordingly, we examined the initial differentiation, developmental regulation, and territorial domain of cardiac SIF cells for comparison with their cholinergic neuron neighbors. Adrenergic SIF cells were present during the time when the first cholinergic precursors were becoming postmitotic. Although SIF cells were present first, cholinergic neurons differentiated almost 16 times faster during the first week of embryonic and larval development and outnumbered SIF cells at all subsequent stages. Nonetheless, the accumulation of both cell types were correlated, since the ratio of cholinergic neurons to SIF cells remained at approximately 10 to 1 up to adult life. Early in development, SIF cells and cholinergic neurons were clustered in the sinus venosus portion of the atrium. The asymmetric distribution of cholinergic neurons within the atrium was lost but that of the SIF cells was maintained throughout life. These results identify relationships between the morphogenesis of two cell types in an autonomic ganglion and place constraints upon the cellular mechanisms that could produce the cells from their neural crest precursors. PMID- 1874980 TI - Pudendal motor and premotor neurons in the male rat: a WGA transneuronal study. AB - Anatomical studies using retrograde neuronal tracers were carried out to identify pudendal motoneurons and putative lumbosacral interneurons involved in the generation of penile reflexes in the adult male rat (Sprague-Dawley). In agreement with previous studies, injection of the direct neuronal tracers, horseradish peroxidase or fluoro-gold, into the left M. bulbospongiosus (dorsal division) resulted in direct retrograde labeling of motoneurons only in the ipsilateral dorsomedial (DM) nucleus. In contrast, similar injections of the transneuronal tracer, wheat germ agglutinin (WGA), resulted in direct retrograde labeling of ipsilateral DM motoneurons as well as transneuronal labeling of contralateral DM motoneurons and of bilaterally located putative spinal interneurons. The WGA-labeling was determined to be transneuronal by a series of nerve cut experiments. The direct retrograde WGA-labeling of ipsilateral DM motoneurons and the transneuronal WGA-labeling of contralateral DM motoneurons and bilateral putative spinal interneurons occurred with different time courses. Direct retrograde labeling of ipsilateral DM motoneurons was seen at 20 hours survival and persisted up to 7 days survival. The shortest survival period for detecting transneuronal labeling of contralateral DM motoneurons and putative interneurons was 2 days. Transneuronal WGA-labeling of contralateral DM motoneurons was transient in that the intensity of label increased from 2 to 3 days survival but was markedly reduced at 7 days survival. At the same time, the number of WGA-labeled putative interneurons increased with longer survival times up to 7 days. WGA-labeled putative interneurons were located primarily in regions receiving dendritic projections from WGA-labeled DM motoneurons and, in particular, 1) the ventral gray matter between the DM and dorsolateral nuclei and 2) near the central canal and extending dorsally to the dorsal gray commissure. The rapid and extensive transneuronal transport between DM nuclei suggests that direct synaptic coupling may mediate coordinated, bilateral activation of DM motoneurons. PMID- 1874981 TI - Parabrachial nucleus projection towards the hypothalamic supraoptic nucleus: electrophysiological and anatomical observations in the rat. AB - It has been proposed that the pontine parabrachial nucleus (PBN) participates in the regulation of body fluid balance and the release of vasopressin from the neurohypophysis, although the pathways mediating the latter response are uncertain. This study in the rat, utilizing anatomical and electrophysiological methods, describes a projection from the lateral PBN towards the hypothalamic supraoptic nucleus (SON). Rats received iontophoretic injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L, 2% solution). After 14-17 days, rats were sacrificed and their brains prepared for immunofluorescent visualization of projections to the SON region. PHA-L-labelled terminals were found primarily in perinuclear regions immediately dorsal to the SON. In contrast, injections within the medial PBN and the nearby Kolliker-Fuse nucleus did not reveal labelling in or around the SON. Extracellular recordings from 86 of 118 antidromically identified neurons in anaesthetized rats revealed a set of complex synaptic responses after stimulation in the PBN. Excitatory responses (in 82 of 86 cells) of short (less than 100 msec, 39/82 cells) and long (greater than 100 msec, 43/82) duration were observed in both vasopressin- and oxytocin secreting cells of the SON, while 4/86 cells displayed a depressant response to PBN stimulation. In the adjacent perinuclear zone, 22/39 nonneurosecretory cells responded with an increase in their excitability consequent to an identical stimulus. These data suggest a predominantly facilitatory influence of lateral PBN neurons on SON neurosecretory cells in the rat, and that the PBN-SON projection is an indirect one that utilizes an interneuronal network located in the perinuclear zone adjacent to the SON. PMID- 1874982 TI - Glomerular lesions in spontaneously occurring diabetic WBN/Kob rats. AB - Glomerular lesions in WBN/Kob male rats with spontaneous diabetes were examined histopathologically. The glomerulopathy caused by diabetes was compared with lesions in chronic progressive nephropathy of non-diabetic SD and F344 male aged rats. Diffuse and global thickening of the mesangial area was observed only in WBN/Kob rats and showed a statistically significant correlation with serum glucose concentrations. Therefore, it suggested that the mesangial thickening was a result of hyperglycaemia. Fibrin cap-like lesions were seen in both WBN/Kob and non-diabetic SD or F344 male rats. The severity of these lesions was closely related to that of chronic progressive nephropathy and, therefore, the fibrin cap like lesions were considered to be due to the chronic progressive nephropathy. PMID- 1874983 TI - Acute disseminated Aspergillosis in a cow with special reference to penetration and spread. AB - Acute disseminated aspergillosis caused by Aspergillus fumigatus is reported in a 4-year-old cow given broad spectrum antibiotics and anti-inflammatory therapy. All stomach compartments were infected and hyphal invasion of gastric blood vessels was the probable source of generalization to the liver, lung and kidneys. Throughout the Peyer's patches of the jejunum there were acute necrotic foci with Aspergillus hyphae and similar foci occurred in the corresponding mesenteric lymph nodes. This points to the Peyer's patches being a portal of entry for A. fumigatus to the lymphatic system of the intestine. PMID- 1874984 TI - Interference with sawfly (Arge pullata) poisoning in Fasciola hepatica-infected lambs. AB - Lambs harbouring an 8-week-old infection with Fasciola hepatica, together with fluke-free animals, were dosed orally with 2 g per kg body weight of sawfly larvae (Arge pullata). Fluke-free, non-dosed lambs and lambs infected only with F. hepatica served as controls. Clinico-pathological observations on sawfly dosed, fluke-free lambs revealed the characteristic picture of sawfly poisoning. Four of six animals had to be killed in extremis. In contrast, sawfly-dosed, fluke-infected lambs exhibited only moderate clinico-pathological signs of sawfly poisoning and no deaths occurred. A reduction in the sawfly-induced liver pathology as a consequence of the concurrent F. hepatica infection was also noted. Possible factors responsible for the antagonistic effect of F. hepatica infection on sawfly poisoning in lambs are discussed. PMID- 1874985 TI - In vitro magnesium- and calcium-induced sialidase activity in caprine intestinal mucosa cells. AB - Sialidase activity identical to 0.0196 mg per ml of liberated sialic acids (2.11 Units) was detected in small intestinal contents of goats. Mg++ and Ca++ induced in vitro detection in mucosa cells of both small and large intestines. Magnesium alone induced sialidase activities identical to 0.0128 mg per ml of liberated sialic acids (1.38 Units) and 0.0166 mg per ml (1.79 Units) in small and large intestinal mucosal cells, respectively. Mg++ and Ca++ together induced higher sialidase activities identical to 0.0191 mg per ml (2.06 Units) and 0.0194 mg per ml (2.09 Units) in small and large intestinal mucosal cells, respectively. The enzyme activity was slightly higher in large than in small intestinal mucosal cells. The results are discussed in relation to control of African animal trypanosomiasis. PMID- 1874986 TI - Primary intra-osseous carcinoma of the maxilla in a horse. AB - An 8-year-old Hannoverian horse developed a swelling of the maxilla caused by a tumour of the hard palate. On histological examination the tumour was diagnosed as a primary intra-osseous carcinoma of the maxilla, a rare odontogenic tumour not previously described in the horse. PMID- 1874987 TI - Spontaneous rete testis adenocarcinoma in a Fischer 344 rat: a cytomorphological and ultrastructural study. AB - The report consists of a cytomorphological and ultrastructural description of a spontaneous rete testis adenocarcinoma observed in a 108-week-old Fischer 344 rat. This tumour is considered to be very rare in rats. Crucial evidence for the malignancy of this tumour was the penetration of a neoplastic gland into the tunica albuginea. PMID- 1874988 TI - [Fear of children at the dental office. A pain that isn't without remedy]. AB - Fearful children in the dental office is an old problem which the majority of dentists have to face in their daily practice. With the help of a brief review of the literature, diverse strategies employed to adjust to the different behavior patterns of children in the dental office are detailed. Furthermore, to illustrate several of the techniques proposed, we have during the month of May 1990, systematically filmed different behavior patterns of children in the waiting room, as well as, in the dental operatory. The material thus obtained, permitted the production of videocassettes on the following themes: "How to approach the child in the dental office?"; "How to treat the young anxious child or a child with a difficult behavior pattern?"; "The first visit to the dentist"; "How to present dental injections?"; "The presence of parents in the dental operatory"; and, "Preventive dentistry". These cassettes are meant for dentists, hygienists, dental assistants, as well as, dental students. Moreover, in the hands of parents, this material answers their numerous questions. Each individual will find something in these presentations, or at least some areas for future exploration. PMID- 1874989 TI - Unwarranted and unprofessional--the superfluous removal of clinically acceptable amalgams. PMID- 1874990 TI - Are "fetal protection policies" just and effective? PMID- 1874991 TI - Use of legislation to assure the quality of mammography. PMID- 1874992 TI - Cardiovascular drugs: the urgent need for studies in women. AB - Most clinical decisions about the choice and dosage of drugs given to women with cardiovascular disease are based on studies that were conducted predominantly or exclusively on middle-aged men. Gender differences, when examined, suggest that the hormonal status, older age, and lesser body mass of women, among other features, may be important contributors to the variability in drug levels, efficacy, side effects, and toxicity. Gender-related considerations in pharmacotherapeutic research have the potential to improve the treatment of women with cardiovascular illness. PMID- 1874993 TI - Gender bias against and sexual harassment of AMWA members in Massachusetts. AB - Despite the increasing participation of women in medicine over the past few decades, hindrances to professional advancement for women physicians and medical students persist. The present study sought to assess the prevalence of gender bias and sexual harassment in a sample of women physicians and medical students. Within a one-year period, 54% of respondents encountered some form of sex discrimination. In addition, approximately one-fourth experienced sexual harassment (27%) and/or discrimination related to parenthood (24%). Unwanted sexual attention not viewed as sexual harassment was experienced by more than twice as many respondents (55%). Other forms of discrimination were reported as well: age (22%), sexual preference (20%), and race (7%). Perceptions of the extent of sex discrimination and sexual harassment, of their impact on professional commitment, and of the adequacy of solutions at institutions varied directly with whether or not respondents had experienced some form of employment discrimination within the past 12 months. This study points to the need for clarification of what constitutes sexual harassment and for the creation of safe, effective mechanisms to remedy and prevent all forms of gender bias. PMID- 1874994 TI - Female condoms, an urgent need. PMID- 1874995 TI - Comparison of the mechanical and histologic properties of Achilles tendons in New Zealand white rabbits secondarily repaired with Marlex mesh. AB - Over the years, there have been numberous reports on the treatment of tendo Achillis ruptures. Most of these dissertations have dealt with the treatment of acute ruptures versus the more technically challenging, neglected, ancient rupture. This paper will focus on the neglected rupture, with specific attention directed towards a new technique of surgical repair, using Marlex mesh. Through the exhaustive testing of the tendo Achillis of New Zealand white rabbits at intervals of 1, 3, and 6 months postimplantation, and subsequent implantation in a 13-month follow-up in an adult, it has been demonstrated that this biosynthetic tendon complex very closely approximates the physical properties of the normal tendo Achillis. Furthermore, through the use of histologic examination, it has been shown that this material actually forms a frame or bridgework for ingrowth of normal, orderly, collagen bundles, closely resembling those found in the original tendinous structure. PMID- 1874996 TI - A new classification for traumatic dislocations of the first metatarsophalangeal joint: type IIC. AB - The anatomy, mechanism of injury, and radiographic diagnosis of traumatic dislocation of the first metatarsophalangeal joint are discussed. Previously, three basic types of these dislocations have been described. The authors propose an additional classification which has not been previously reported. PMID- 1874997 TI - Carbon dioxide laser management of plantar verruca: a 6-year follow-up survey. AB - Patients receiving treatment for plantar verruca by carbon dioxide laser vaporization from 1984 through 1989 were surveyed with follow-up from 3 months to 6 years. Materials and methods, operative technique, and results were reviewed. This procedure was used as both a primary treatment as well as secondary or tertiary treatments on recalcitrant verrucae. Solitary as well as multiple or mosaic lesions were evaluated. Patients were surveyed for elimination of all verrucae, partial or complete recurrence, postoperative complications, and satisfaction. The overall success rate, considering all eight treatment categories, was 75%. Ultimate success rates ranged from 93% for solitary lesions to 62% for multiple recalcitrant lesions. The authors' findings show clinical significance in the marked differentiation of success rates in accordance with the classification scheme. That is to say, initial treatment of a solitary lesion showed a higher success rate than initial treatment of multiple lesions, and initial treatment of virgin lesions showed a higher success rate than initial treatment of recalcitrant lesions. Based on the data accumulated, the authors propose that treatment of plantar verruca be initiated early, i.e., while the lesion is solitary and has been heretofore untreated. On the other hand, those lesions having a second or third treatment by carbon dioxide laser vaporization resulted in a higher ultimate success rate than those which had only one primary treatment. The general conclusion is that carbon dioxide laser management should be considered as a viable treatment alternative in relation to other, more traditional, techniques in the treatment of plantar verruca. PMID- 1874998 TI - Computed tomography for diagnosis of Morton's neuroma. AB - Fifteen patients suspected to have Morton's neuroma were examined by computed tomography, which revealed the neuroma in seven cases. All seven underwent surgery and had the diagnosis confirmed. If there is doubt about the diagnosis, it is possible to use computed tomography as shown here. PMID- 1874999 TI - Alternative autogenous bone graft donor sites in brachymetatarsia reconstruction: a review of the literature with clinical presentations. AB - The authors present a literature review on the surgical treatment of brachymetatarsia. They discuss the identification of donor sites for autogenous bone graft harvesting from the foot. Three case reports of brachymetatarsia, one of iatrogenic, and two of congenital origin are presented. PMID- 1875000 TI - Periungual bacterial flora in the human foot. AB - Proper presurgical preparations are presumed to eliminate organisms from the skin, nails, and nail grooves. It has not been documented as to whether surgical scrubs reduce the types and numbers of bacteria and thereby affect the incidence of infection in performing toenail surgery. This study, performed pre- and postsurgical scrub cultures of four sites on 40 subjects. Similar cultures from ten additional patients who underwent nail surgery were also performed. The later set had an additional set of cultures performed after avulsion of the nail plate and the beginning of the actual surgical procedure. Blood cultures were done intraoperatively on the surgical patients. Results revealed that nail grooves are difficult, if not impossible, to antisepticize. The usual presurgical scrub does not eradicate bacteria in these areas. As such, nail surgery must certainly be considered dirty surgery and precautionary measures must be considered. PMID- 1875001 TI - Hallux varus: a step-wise approach for correction. AB - Iatrogenic hallux varus can be an unfortunate complication of hallux abducto valgus surgery. The correction of hallux varus must be performed in a well planned, step-wise method. The authors present both soft tissue and osseous corrections for hallux varus, with two case reports. PMID- 1875002 TI - Epidural morphine as an adjuvant to the treatment of pain in a patient with acute inflammatory polyradiculopathy secondary to Guillain-Barre syndrome. AB - The authors discuss a case of acute inflammatory polyradiculopathy in a patient with Guillain-Barre syndrome. Consultation with podiatry was requested in an effort to remit the severe lower extremity symptoms. Treatment using epidural morphine with subsequent results is discussed. It is the authors' opinion that Guillain-Barre syndrome is the most common acutely or subacutely evolving inflammatory, demyelinating, neuropathy in the United States. PMID- 1875003 TI - Fifth metatarsal head resection for correction of tailor's bunions and sub-fifth metatarsal head keratoma: a retrospective analysis. AB - A variety of surgical procedures traditionally have been employed in the treatment of tailor's bunions and sub-fifth metatarsal head keratomas. The overwhelming majority of literature on this subject evaluates the advantages and disadvantages of various fifth metatarsal osteotomies. The authors have initiated a preliminary investigative study to evaluate the effectiveness of fifth metatarsal head resection and to compare these results with those of other studies that have focused on osteotomy techniques. Subjective and objective analyses of 50 procedures (34 patients) were performed retrospectively. Patients were either satisfied or very satisfied in 84% of the cases reviewed. Symptomatic transfer lesions occurred in only 3% of all feet examined. The most frequent postoperative complication was that of fifth digital malalignment, which presented in nearly 60% of the cases. The procedure possesses advantages and disadvantages, which prior to this study, have been discussed in anecdotal fashion only. PMID- 1875004 TI - Chevron osteotomy in the treatment of hallux valgus. AB - Fifty patients who underwent 80 chevron osteotomies for symptomatic hallux valgus were re-examined and assessed 4 years and 7 months (average) after surgery. Forty five of the patients were satisfied with the result of their surgery, three patients suffered recurrence of their deformity and two had continuance of their symptomatology. The major complications noted were intraoperative intra-articular fracture of the metatarsal head in five feet, loss of initial repair in three feet, and tilt of the distal fragment (metatarsal head) in two feet. The Chevron osteotomy is a relatively simple procedure that corrects the varus deformity of the first metatarsal, realigns the valgus orientation of the metatarsal head, corrects the hallux valgus deformity, and improves symptomatology. PMID- 1875005 TI - Calcifying aponeurotic fibroma. AB - The calcifying aponeurotic fibroma is a rare, benign neoplasm that often presents in the palms or soles of young male children. Microscopic examination of this tumor demonstrates atypical fibroblasts, foci of calcification, and patches of chondroid differentiation. The neoplasm's highly cellular architecture, locally aggressive growth pattern, and tendency to recur may lead to a misdiagnosis of fibrosarcoma and subsequent amputation. This manuscript presents a review of the literature and a unique case involving the digits of the foot. PMID- 1875006 TI - Flexor hallucis brevis muscle flap. AB - The use of muscle flaps for treatment of chronic wounds has become more widespread. The specific use of intrinsic muscle flaps of the foot for treatment of diabetic ulcerations has the potential to provide alternative ways of avoiding amputations. A case report is presented that illustrates the use of the flexor hallucis brevis flap for a chronic ulceration beneath the first metatarsal head. The technique and indications are discussed. PMID- 1875007 TI - Titanium hemi-great toe implant: a preliminary study of its efficacy. AB - The purpose of this preliminary study is to evaluate the effectiveness of the titanium hemi-great toe implant. The device is found to be successful in helping to treat painful degenerative joint disease of the first and second metatarsophalangeal joints. The implant's most promising application appears to be use in patients below the age of 50 years manifesting metatarsophalangeal joint dystrophy, with subsequent clinical debilitation, who become surgical candidates. PMID- 1875008 TI - Magna-FX cannulated screw system and powered metaphyseal stapler in triple arthrodesis. AB - The author introduces two relatively new means of internal fixation for triple arthrodesis. These new methods not only help to reduce intraoperative time, but also provide an excellent, more precise method of internal fixation. A case report and discussion on the use of these devices are included. PMID- 1875009 TI - Assessing the effects of pentoxifylline (Trental) on diabetic neurotrophic foot ulcers. AB - The effects of pentoxifylline (Trental) on diabetic neurotrophic foot ulcers was assessed. Twelve insulin-dependent diabetics were evaluated. Each patient had a peripheral neuropathy with secondary neurotrophic ulceration involving the foot. The ulcers were treated using conservative care for at least 3 months prior to entering the patient in the study. During this time, no appreciable decrease in ulcer size was observed. Prior to commencement of the study, the critical closing pressure of the involved foot and the ulcer size were measured and recorded. Six months later these measurements were repeated. Of the 12 patients who started pentoxifylline, nine finished. The remaining three patients completed the study but had discontinued the medication. Of the nine patients finishing the study and taking pentoxifylline, eight ulcers completely healed, with the remaining one having decreased in size. The average critical closing pressure increased 11 mm. Hg. Pentoxifylline appeared to have accelerated the healing process in the nine diabetic ulcer patients. PMID- 1875010 TI - True aneurysm of the dorsalis pedis artery mimicking a soft tissue tumor. AB - The clinician must be very suspicious in differentiating soft tissue masses on the dorsum of the foot. Radiologic aids are often nonspecific in providing an identity. Surgical expectations may also be altered, as in this case described of an atypical aneurysm of the dorsalis pedis artery. PMID- 1875011 TI - Management of the anticoagulated patient for elective surgery. AB - The authors discuss treatment of the anticoagulated patient prior to elective surgery. They review factors that increase and decrease patient response to this therapy. Recommended procedure for dealing with the anticoagulated surgical patient is then presented. PMID- 1875012 TI - Injuries to the talus-neck fractures and osteochondral lesions (osteochondritis dissecans). AB - The authors discuss pathology to the talus, as determined radiographically. They review pertinent anatomy, including blood supply to this bone. Fractures are categorized, with a review of clinical management. PMID- 1875013 TI - Saphenous and common peroneal nerve block will prevent tourniquet pain in prolonged podiatry procedures. PMID- 1875014 TI - Ultrasonic and endocrinologic aspects in gonadotropin releasing hormone induction of ovulation. AB - Ovarian growth, follicular size, 17 beta-estradiol (E2), androstenedione (A) and testosterone (T) peripheral levels were evaluated in 12 hypogonadotropic patients during the follicular phase on 12 cycles of pulsatile GnRH iv administration. During GnRH therapy, significant correlations between E2 plasma levels and volume of the dominant follicle (p less than 0.001) as well as total follicular volume (p less than 0.001) and total ovarian volume (p less than 0.01) were found. Plasma A was significantly related to the ultrasonic changes of ovarian stroma and those follicles which usually fail to ovulate. Plasma T showed a significant correlation with ovarian stroma (p less than 0.05). Significant correlations of E2/A and E2/T peripheral ratios with volume of the dominant follicle (p less than 0.01) were also found. In spontaneous ovulatory cycles, similar correlations between endocrine and morphological parameters have been already published. The findings of the present investigation indicate that in spontaneous and GnRH induced cycles the endocrine events associated to the follicular development are quite similar. In hypogonadotropic patients, a "normal" follicular maturation may be obtained by means of this therapy. PMID- 1875015 TI - Erythrocyte and platelet fatty acids in retinitis pigmentosa. AB - The fatty acid composition and the glutathione-peroxidase activity (GSH-Px) of erythrocytes and platelets, the production of malondialdehyde (MDA) by platelets and the activity of the main systems of transmembrane cation transport in erythrocyte have been studied in 12 patients (5 males and 7 females) affected by retinitis pigmentosa (RP). A remarkable increase of saturated fatty acids (SFA), particularly of stearic acid (C18:0), has been noted in these patients. The reduced unsaturated/saturated fatty acids ratio (PUFA/SFA) observed in both erythrocytes and platelets and the decrease of arachidonic acid in platelets may depend by an active peroxidation process as documented by the increase of MDA. Platelet glutathione-peroxidase (PTL-GSH-PX) and plasma retinol were in the normal range, whereas erythrocyte glutathione-peroxidase (E-GSH-PX), MDA and plasma alfa-toco-pherol were increased in patients with RP. The activities of Na(+)-K+ pump, cotransport and Na(+)-Li+ countertransport were normal in RP erythrocytes. PMID- 1875016 TI - Involvement of interleukin-1 in the inhibition of in vivo insulin release: possible role of adrenal glands. AB - The effect of recombinant human interleukin-1 beta (rhIL-1b) on in vivo insulin secretion was examined in intact and adrenalectomized (ADX) rats under conscious and pentobarbital anesthetized conditions. In conscious rats, rhIL-1b dose dependently decreased blood glucose levels at 2 h in both groups and significantly inhibited insulin release only at doses of 1 and 10 micrograms/kg in ADX rats. Under pentobarbital anesthesia, rhIL-1b administration decreased blood glucose levels 2 h later in both intact and ADX rats and resulted in severe hypoglycemia in ADX rats. At 2 h later, rhIL-1b significantly suppressed insulin release by pentobarbital injection in both intact and ADX rats. It is concluded that rhIL-1b suppresses in vivo insulin secretion in conscious ADX and anesthetized rats. PMID- 1875017 TI - 1,25-Dihydroxycholecalciferol inhibits the cochemotactic activity of Gc (vitamin D binding protein). AB - The identification of Gc (vitamin D binding protein) with the anionic polypeptide cochemotaxin has recently been reported. In this paper we investigate its dose dependent cochemotactic activity and report the inhibition of Gc enhanced chemotaxis by vitamin D3. These results further support the role of immunomodulating hormone played by vitamin D. PMID- 1875018 TI - Thyroid hormone metabolism and nuclear binding in Gunn rats. AB - We examined the serum concentrations of total, free thyroid hormones and TSH, activity of hepatic T4 5'-deiodinase, and T3 binding to hepatic nuclei in homozygous (j/j) and heterozygous (j/+) Gunn rats. Both total T3 and free T3 (FT3) concentrations in sera from j/j rats were significantly lower than those of j/+ rats on 5-10, 15-20, and 25-30 days after birth. Both total T4 and free T4 (FT4) concentrations in j/j and j/+ rat sera were not significantly different on 5-10 days. However, in j/j rats they were significantly higher than those of j/+ rats on days 15-20 and 25-30. Serum reverse T3 (rT3) concentrations were higher in j/j than in j/+ rats on days 5-10, 15-20, and 25-30. Serum TSH concentration in j/j and j/+ rats on 15 days post-natal were 1.42 +/- 1.28 and 1.65 +/- 1.24 micrograms/l (mean +/- SD), respectively, which were not significantly different from each other. T3 formation from T4 in hepatic microsomal fractions obtained 15 days after birth was significantly lower in homozygotes than in heterozygotes (4.89 +/- 1.18 vs 11.15 +/- 2.38 pmol/mg protein/min, p less than 0.005). Binding constants (Ka) as well as maximal binding capacities (MBC) for T3 of hepatic nuclei from 15 day-old j/j and j/+ rats were similar (ka; 3.58 x 10(9) vs 3.15 x 10(9) M-1, MBC; 0.316 vs 0.380 pmol/mg DNA). From these results we suggest that decreased conversion from T4 to T3 is one of the major reasons for high serum levels of T4 and rT3, and low levels of T3 in j/j rats, and that nuclear T3 binding and pituitary TSH secretion are unaltered in j/j rats. PMID- 1875019 TI - Iodine prophylaxis in schoolchildren residing in the province of Parma, Italy. PMID- 1875020 TI - Update on pulsatile luteinizing hormone-releasing hormone therapy in males with idiopathic hypogonadotropic hypogonadism and delayed puberty. PMID- 1875021 TI - Publishing in biomedical journals: The system in review. PMID- 1875022 TI - Organic acidurias: a review. Part 1. AB - Organic acidemias are disorders of intermediary metabolism that lead to accumulation of organic acids in biologic fluids, disturb acid-base balance, and derange intracellular biochemical pathways. Their clinical presentation reflects the resultant systemic disease and progressive encephalopathy. While in some organic acidemias, disturbed acid-base metabolism is the predominant presenting feature, in others it is less prominent or even absent. The etiologies of the more than 50 different phenotypes include impaired metabolism of branched-chain amino acids, vitamins, glucose, lipids, glutathione, and gamma-aminobutyric acid and defects of oxidative phosphorylation. Most organic acidemias present with neurologic manifestations, which include acutely or subacutely progressive encephalopathy that involves different parts of the nervous system. The age of presentation and the associated systemic, hematologic, and immune findings provide additional guidelines for differential diagnosis. We summarize major organic acidemias, while emphasizing their usual and unusual neurologic presentations. PMID- 1875023 TI - Multiple sulfatase deficiency with early severe retinal degeneration. AB - We report an unusual case of multiple sulfatase deficiency in which neurodegeneration was accompanied by early, severe visual impairment associated with prominent pigmentary retinopathy, suggesting a diagnosis of neuronal ceroid lipofuscinosis. The levels of arylsulfatases A, B, and C, heparan N-sulfatase, N acetylgalactosamine-6-sulfate sulfatase, and iduronate-2-sulfate sulfatase were all markedly decreased in cultured skin fibroblasts. Screening tests for mucopolysacchariduria were consistently negative; however, thin-layer chromatographic analysis of isolated urinary glycosaminoglycans showed increased amounts of heparan sulfate. PMID- 1875024 TI - Morris James Lewis (1852-1928) and the description of the jaw jerk. PMID- 1875025 TI - Cerebral blood flow and oxygen metabolism in rett syndrome. AB - Positron emission tomography was performed on six patients with Rett syndrome to investigate cerebral blood flow and oxygen metabolism, and the results were compared with the concurrent clinical status of the patients. The cerebral metabolic rate of oxygen (CMRO2) was low in five patients, and oxygen extraction fraction was low in four patients; both had a tendency to decline with advancing age. Although the cause is unknown, it is suggested that impaired oxidative metabolism exists in Rett syndrome. An analysis of the distribution among brain regions showed that the ratios of values for the frontal cortex to those for the temporal cortex for both cerebral blood flow and CMRO2 were lower than those for the controls, which may indicate the loss of hyperfrontality in Rett syndrome. PMID- 1875026 TI - Jitteriness beyond the neonatal period: a benign pattern of movement in infancy. AB - Jitteriness is a frequent, well-recognized phenomenon in neonates. Its occurrence in early infancy, beyond the neonatal period, is much less documented. Thirty eight full-term infants who were jittery after 6 weeks of age were followed until the jitteriness disappeared and then reevaluated at the age of 3 years. The jittery movements had already been observed during the neonatal period in 16 babies but not before 6 weeks of age in 22. In 34 infants (89%), 1- and 5-minute Apgar scores were 9 or 10. At the initial examination, a mildly increased muscle tone was found in 12 infants, and hyperactive deep-tendon reflexes were found in 19. The jitteriness resolved at a mean age of 7.2 +/- 3.4 months. At 3 years, 92% of the infants had a normal neurodevelopmental examination, while in the rest only minor, transient disturbances were found. This study indicates that jitteriness as a sole presentation in infants beyond the neonatal period is a benign phenomenon, associated with an excellent prognosis. Its etiology is unknown but seems most likely to be related to a maturational process within the central nervous system. PMID- 1875027 TI - Simultaneous infantile spasms and partial seizures. AB - We report 11 infants with infantile spasms who had partial seizures that occurred concurrently with the infantile spasms. We studied this phenomenon with time locked video electroencephalography. The partial seizures began before the infantile spasms and continued after one or more infantile spasms in seven patients. An infantile spasm occurred at the beginning of the partial seizure in five patients. (One patient had both seizure types simultaneously.) The clinical descriptions of these combinations of seizures were confusing, since they did not match known seizure types. The genesis of these seizures may involve an interaction between processes of focal cortical epileptogenesis (partial seizures) and brain-stem synchronization (infantile spasms). PMID- 1875028 TI - A Japanese family with two types of muscular dystrophy: DNA analysis and the dystrophin test. AB - A unique Japanese family with both Fukuyama type congenital muscular dystrophy (FCMD) and Duchenne muscular dystrophy (DMD) is described. Four boys, all from the sixth generation of the same family, were afflicted with severe neuromuscular diseases beginning in early life, three of them presenting the typical phenotype of FCMD and one, that of DMD. Although DNA analysis by Southern blotting with complementary DNAs representing the whole of the dystrophin coding sequence detected neither gross deletions nor duplications, immunohistochemistry and Western blotting of the biopsied skeletal muscle with an antidystrophin monoclonal antibody (dystrophin test) showed that the approximately 400-kd dystrophin was expressed normally at the sarcoplasmic membrane of the FCMD phenotype patient but was completely absent in the DMD phenotype patient. From these results, it was presumed that two different childhood muscular dystrophies, FCMD and DMD, coexisted in this family. This unique case illustrates the efficacy of the dystrophin test in the differential diagnosis of the two diseases even when conventional means of diagnosis do not give definite answers and DNA analysis of the dystrophin gene is not informative. PMID- 1875029 TI - Cerebrospinal fluid beta-endorphin and cortisol study in Rett syndrome. AB - An evaluation of cerebrospinal fluid and plasma beta-endorphin and cortisol levels was performed in 15 girls affected with classic Rett syndrome. There were no differences between the patient group and the control group in plasma cortisol and beta-endorphin levels. But in Rett syndrome, a significant increase in beta endorphin was noted in the cerebrospinal fluid, with an elevation of the cerebrospinal fluid/plasma beta-endorphin ratio and a decrease in cerebrospinal fluid cortisol. A substantial overlap between patients and control group diminishes the diagnostic value of cerebrospinal fluid beta-endorphin assay in girls suspected of having Rett syndrome. PMID- 1875030 TI - Clinical features and magnetic resonance imaging in congenital and childhood stroke. AB - Fifty-three (5%) of 1064 consecutively imaged children showed an arterial vascular pattern on magnetic resonance images, accounting for 12% of all abnormal studies. Signal abnormalities on T2-weighted scans persisted years after the clinical stroke occurrence. Ipsilateral atrophy of the pons or midbrain was found in 25% of subjects and was strongly associated with congenital lesions. Most infarctions occurred before or during the neonatal period; only 31% were acquired later. We did not find the paucity of posterior circulation lesions or the marked excess of left middle cerebral artery lesions seen in other series. Cardiac disease and venous infarction had an unexpectedly low occurrence. All of the children with arterial border zone infarction had been resuscitated in the neonatal period, while 37% of the children with a single artery infarction had no clinical history of acute illness. PMID- 1875031 TI - The future of child neurology. PMID- 1875032 TI - Spasticity in cerebral palsy and the selective posterior rhizotomy procedure. PMID- 1875033 TI - Central respiratory dysfunction in Mobius syndrome. PMID- 1875034 TI - Proceedings of the John Elgin Patrick memorial symposium. PMID- 1875035 TI - The science and practice of John Patrick: the connection between Oxford, London and Maastricht. PMID- 1875036 TI - Lifestyle influences on prematurity. AB - It is apparent from this review that the lifestyle of an individual gravida can potentially lead to a premature delivery. Some of these adverse behavioral characteristics may be dealt with by education and motivation, and some with actual medical treatment. However, there also appears to be significant need for public policy reorientation if we are to make a significant impact on the problem of preterm delivery. PMID- 1875037 TI - Effects of alcohol (ethanol) on the fetus. AB - Alcohol (ethanol) use during pregnancy can produce a wide spectrum of effects in the developing embryo/fetus that are dependent on the maternal drinking pattern. The effects of chronic ethanol exposure on the developing conceptus are reviewed with primary focus on ethanol teratogenesis, manifesting in the human as the fetal alcohol syndrome or fetal alcohol effects. The effects of acute ethanol exposure on the near-term fetus are described, including suppressed fetal breathing movements, electrocorticographic (ECoG) activity and electrooculographic (EOG) activity. The ethanol-induced suppression of fetal breathing movements is a very sensitive index of acute exposure of the near-term fetus to ethanol, and appears to involve a direct mechanism of action rather than an indirect mechanism involving suppression of electrocortical activity. The disposition of ethanol and its pharmacologically active proximate metabolite, acetaldehyde, and the activity of alcohol dehydrogenase and aldehyde dehydrogenase in the near-term maternal-fetal unit are described, and a pharmacokinetic model is proposed. The effects of short-term ethanol exposure on the near-term fetus include the development of tolerance to the ethanol-induced suppression of fetal breathing movements, low-voltage ECoG activity and EOG activity. The development of tolerance occurs more rapidly to the latter two fetal biophysical activities. The mechanism of tolerance development appears to be pharmacodynamic (functional) in nature, as there is no increase in the rate of ethanol elimination from the maternal-fetal unit. The role of prostaglandins (PGs) in the mechanism of the ethanol-induced suppression of fetal breathing movements is described. In the near-term fetus, there is a direct relationship between fetal blood ethanol concentration and fetal plasma PGE2 concentration, and an inverse relationship between the incidence of fetal breathing movements and each of fetal plasma and fetal cerebrospinal fluid (CSF) PGE2 concentrations. Indomethacin, a PG synthetase inhibitor, selectively blocks and reverses the ethanol-induced suppression of fetal breathing movements. These data support the postulates that the ethanol-induced suppression of fetal breathing movements is mediated by increased PGE2 concentration in the near-term fetus and that the ability of indomethacin to antagonize the ethanol-induced suppression of fetal breathing movements is due to its biochemical action to decrease fetal PGE2 concentration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1875038 TI - Exercise and fetal health. AB - This is a brief review of current information dealing with the impact of maternal exercise on the well-being of the human embryo and fetus. It discusses the theoretical concerns and exercise variables involved in the interaction between exercise and fetal health and focuses on five areas of fetal health where some information is available describing the interaction in the human. These include embryonic development, fetoplacental growth, prematurity, indices of fetal stress/distress, and condition during labor and at birth. It concludes that well conditioned women who continue a regular running or aerobics regimen in the peri conceptual period and throughout pregnancy at levels that exceed current guidelines do not experience an increase in the incidence of failure to conceive, abortion, congenital abnormalities, abnormal placentation, premature rupture of the membranes or preterm labor. Although all their fetuses demonstrate a brisk elevation in heart rate post-exercise throughout pregnancy, they have a significant reduction in the incidence of 4 clinical markers of fetal stress/distress during labor. In addition, at the time of delivery, their % body fat is less than that of the control offspring (11 vs 16%) which accounts for over 70% of the observed 300 g reduction in birthweight. Finally, there is little evidence to suggest that the other exercise regimens studied to date have an adverse effect on fetal health. PMID- 1875039 TI - Biochemical identification of alpha-fodrin and protein 4.1 in human keratinocytes. AB - The mature erythrocyte has a cytoskeleton of less complexity than that of nucleated cells and has been elucidated in greater detail. Two of its major components are the heterodimeric protein spectrin and protein 4.1. We report here our isolation from human keratinocytes of immunoreactive forms of both protein 4.1 and of alpha-fodrin, the extra-erythrocytic form of alpha-spectrin. These keratinocyte proteins are approximately 125 kD and 240 kD in size, respectively. We also have isolated clones containing alpha-fodrin and protein 4.1 sequences from a human keratinocyte cDNA library. These sequences confirm the active transcription in keratinocytes of the alpha-fodrin and protein 4.1 genes. Both alpha-fodrin and protein 4.1 mRNA are detectable by Northern blot analysis in human keratinocytes, where their abundance appears not to be regulated by calcium concentration in the medium. PMID- 1875040 TI - Structural aberration of the rough endoplasmic reticulum and melanosome compartmentalization in long-term cultures of melanocytes from vitiligo patients. AB - Long-term cultures of melanocytes were established from 14 subjects with vitiligo and from five normal controls and analyzed ultrastructurally. Cultured melanocytes from 78.6% of the vitiligo patients demonstrated abnormalities that consisted of 1) dilation of the rough endoplasmic reticulum (RER), 2) circular RER profiles, and/or 3) membrane bound compartments of melanosomes. Cultured melanocytes from control subjects were predominantly normal with only one of the normal cultures demonstrating minimal circular RER profiles. The three unique abnormal structures in cultured vitiligo melanocytes were not always concomitantly expressed and could not be associated with any specific clinical feature of vitiligo. Quantitative analysis of the RER demonstrated that the profiles of dilated RER in cultured vitiligo melanocytes expressed a significant 1.5-2.8-times increase in mean cisternal area over cultured control melanocytes (i.e., 5.41-9.92 microns 2 versus 3.53 microns 2, respectively). The cisterna of the dilated RER profiles frequently contained floccular material that appeared to originate from the ribosomes, an indication that the floccular material may be translation products. The dilation of RER in melanocytes from the same patient persisted through repeated subculturing for up to 14.75 months. Epidermal melanocytes in biopsied skin from a patient whose cultured melanocytes were aberrant also demonstrated dilated and circular RER profiles. These results demonstrate that melanocytes from most vitiligo patients express an innate defect when cultured. Although this defect does not appear to be cytotoxic in vitro, this abnormality may be the primary defect that elicits melanocyte destruction in vivo. PMID- 1875041 TI - Disparate antioxidant enzyme activities in cultured human cutaneous fibroblasts, keratinocytes, and melanocytes. AB - Antioxidant enzyme activities of cultured human foreskin fibroblasts, keratinocytes, and melanocytes from healthy black and Caucasian donors were measured and compared. Fibroblasts had more (p less than 0.05) peroxidase, catalase, glutathione peroxidase, and superoxide dismutase activity than keratinocytes. Keratinocytes had more (p less than 0.05) peroxidase, catalase, glutathione peroxidase, and superoxide dismutase activity than melanocytes. No differences in antioxidant enzyme activities were observed between the cells of any type taken from black or Caucasian people. Antioxidant enzyme activities may affect resistance to damage by oxidants induced by ultraviolet radiation and inflammation. PMID- 1875042 TI - Transforming growth factor-beta improves healing of radiation-impaired wounds. AB - Exogenously applied TGF-beta 1 has been shown to increase wound strength in incisional wounds early in the healing process. An impaired wound healing model was first established in guinea pigs by isolating flaps of skin and irradiating the flaps to 15 Gray in one fraction using a 4-MeV linear accelerator. Incisions made 2 d after irradiation were excised 7 d later, and showed decreased linear wound bursting strength (WBS) as compared to non-irradiated control wounds on the contralateral side of each animal (p = 0.001). The effect of TGF-beta on healing of radiation-impaired wounds was studied using this model. Skin on both left and right sides of guinea pigs was irradiated as above. A linear incision was made in each side. Collagen with either 1, 5, or 20 micrograms of TGF-beta was applied to one side prior to closure with staples, whereas the contralateral side received saline in collagen. Wounds given either 1 or 5 micrograms of TGF-beta were found to be stronger than controls at 7 d (p less than 0.05), whereas those receiving the higher 20-micrograms dose were weaker than controls (p less than 0.05). Thus, TGF-beta in lower doses improved healing at 7 d but very large amounts of the growth factor actually impaired healing. In situ hybridization done on wound samples showed increased type I collagen gene expression by fibroblasts in wounds treated with 1 micrograms TGF-beta over control wounds. These results indicate that TGF-beta improved wound healing as demonstrated by increased WBS. This improvement is accompanied by an up-regulation of collagen gene expression by resident fibroblasts. PMID- 1875043 TI - Squamous carcinoma cell lines produce 1,25 dihydroxyvitamin D, but fail to respond to its prodifferentiating effect. AB - The active metabolite of vitamin D3, 1,25 dihydroxyvitamin D3 [1,25(OH)2D], is produced by normal human keratinocytes (NKC) and regulates their differentiation. Squamous carcinoma cell (SCC) lines lack the ability to differentiate in vitro, which might involve defective 1,25(OH)2D synthesis or response. To address this possibility we obtained four SCC lines (12F2, 12B2, 25, and A431) and first determined whether they could produce 1,25(OH)2D from its substrate 25 hydroxyvitamin D3 (250HD). All could (12F2 greater than NKC greater than 25 greater than 12B2 greater than A431). Furthermore, exogenously added 1,25(OH)2D inhibited 1,25(OH)2D production and stimulated 24,25 dihydroxyvitamin D3 [24,25(OH)2D] production in all cell lines but with different potency (25 = A431 greater than NKC greater than 12B2 greater than 12F2). Cellular binding studies suggested that the high-affinity binding site for 1,25(OH)2D in NKC is not found in 12F2 and 12B2. When the effect of 1,25(OH)2D on differentiation was determined, only NKC responded with an increase in cornified envelope formation, although some of the cell lines responded to the proliferative [at low 1,25(OH)2D concentration] or antiproliferative [at high 1,25(OH)2D concentration] effect of 1,25(OH)2D. Thus, although SCC lines synthesize 1,25(OH)2D and respond to exogenous 1,25(OH)2D with respect to appropriate regulation of endogenous 250HD metabolism, these cell lines fail to respond to the differentiating influence of this vitamin D metabolite. PMID- 1875044 TI - Characterization of glutathione S-transferase in cultured human keratinocytes. AB - The glutathione S-transferase activity and isozymic composition of cultured human keratinocytes were characterized. Keratinocytes were grown in culture and harvested at different stages of differentiation. Glutathione S-transferase activity was found in the soluble cell fraction but not in the microsomal cell fraction. The glutathione S-transferase specific activity of the soluble cell fraction was found to increase as the keratinocytes differentiated in culture. All of the enzymatic activity was found to reside with a single isozymic form that was concluded to be the pi form of the enzyme based on substrate specificity, sensitivity to inhibitors, molecular weight, and reactivity towards antibodies raised to alpha, mu, and pi forms of the enzyme. It is concluded that all of the isozymic forms of glutathione S-transferase noted in whole skin, with the exception of pi, are of extra-keratinocyte origin. PMID- 1875045 TI - In vitro cutaneous biotransformation of propranolol. AB - The metabolism of propranolol by human skin and by several cell preparations has been investigated in vitro. The major metabolites produced by human skin in organ culture and by keratinocytes were N-desisopropylpropranolol (DIP), propranolol glycol (GLY), and naphthoxylactic acid (NLA). Formation of GLY and NLA was linear with incubation time up to 6 d and was directly proportional to propranolol concentration. Fibroblasts and melanocytes also produced GLY and NLA, but appeared to have lower propranolol-biotransforming activity than keratinocytes. The three metabolites detected arise from side-chain oxidation of propranolol, and the use of specific enzyme inhibitors determined that monoamine oxidase and cytochrome P450 isozymes are involved in their formation. Aldehyde and alcohol dehydrogenases are also probably involved in the formation of NLA and GLY, but attempts to inhibit these enzyme systems were inconclusive, possibly due to the chemical instability of the intermediate aldehyde resulting from monoamine oxidase activity. No evidence was found for conjugation or ring oxidation by the skin or isolated cells. Induction of keratinocyte differentiation with Ca++ or phorbol ester treatment resulted in an increase of overall biotransformation and the NLA/GLY ratio. PMID- 1875046 TI - T-lymphocyte-activating properties of epidermal antigen-presenting cells from normal and psoriatic skin: evidence that psoriatic epidermal antigen-presenting cells resemble cultured normal Langerhans cells. AB - Fresh and cultured human Langerhans cells display disparate functional programs, based on their capacities to activate autologous and allogeneic T cells, and with respect to their susceptibility to inhibition by transforming growth factor-beta (TGF beta). We have compared the functional properties of epidermal antigen presenting cells (APC) procured from uninvolved and involved skin of patients with psoriasis with fresh and cultured normal epidermal cells. Freshly obtained psoriatic epidermal APC resembled cultured normal epidermal cells in their superior capacity to activate syngeneic and allogeneic T cells; fresh normal epidermal cells failed to activate syngeneic T cells, and induced only modest proliferation among allogeneic T cells. The modest T-cell--activating properties of fresh, normal epidermal cells were not suppressed by TGF beta, whereas the T cell--activating potential of psoriatic epidermal cells, cultured normal epidermal cells, and blood APC was inhibited approximately 50% by TGF beta. Thus, fresh psoriatic epidermal APC resemble cultured normal epidermal cells functionally. Because these properties are already evident in cells obtained from uninvolved psoriatic skin, the "cultured" functional phenotype of epidermal APC in this disease may precede the appearance of active psoriatic skin lesions. Surface marker analysis of normal and psoriatic epidermal cell suspensions revealed that virtually all of the bone marrow--derived cells in normal epidermal cell suspensions were conventional (CD1+) Langerhans cells, whereas CD1+ cells comprised only a minority of bone marrow--derived (CD45+) cells in psoriatic epidermis. It is speculated that some of the CD1-, CD45+ cells in psoriatic epidermis may be Langerhans cells that have lost their "fresh" phenotype. These data indicate that an abnormality in epidermal APC function exists in psoriatic skin--even before clinical lesions develop, and we speculate that the abnormal capacity of psoriatic epidermal APC to activate syngeneic T cells may be important in the expression of keratinocyte pathology. Because psoriatic epidermal APC functions were profoundly inhibited in vitro by treatment with cyclosporin A, the effectiveness of this drug in psoriasis may be due in part to its ability to inhibit epidermal antigen-presenting cell function in vivo. PMID- 1875047 TI - A successful murine model for contact sensitization to a sesquiterpene-alpha methylene-gamma-butyrolactone: sensitization to alantolactone in four strains of mice. AB - Induction of allergic contact hypersensitivity to a sesquiterpene lactone, alantolactone, was studied in four strains of mice: C3H/He, DBA/2, Balb/b, and Balb/c. The last three were successfully sensitized. A significant dose/response was demonstrated in these species, as well as an experimental "overload effect" in Balb/c and Balb/b strains. Histologic studies confirmed the allergic nature of the reaction. From the overall results, alantolactone can be considered a moderate sensitizer in mouse as well as in guinea pig. This study shows that the murine model can be used for experimental contact sensitization with moderate allergens, without the use of Freund's adjuvant for induction. PMID- 1875048 TI - DNA image cytometry of keratoacanthoma and squamous cell carcinoma. AB - The distinction between the keratoacanthoma (KA) and the squamous cell carcinoma (SCC) can sometimes be difficult on the basis of histologic and clinical criteria. The possible diagnostic significance of DNA ploidy initiated the present study evaluating the DNA ploidy in paraffin-embedded tissue sections of 7 KA and 15 SCC, and fresh frozen tissue touch preparations of 15 of the same cases using the CAS 200 Image Analyzer. In paraffin-embedded tissue sections the main peak DNA index was based on normal epidermis, and ranged from 1.03 to 1.59 in KA and from 1.47-2.71 in SCC. The DNA Index (DI) discriminated KA from SCC in 17 of 22 cases (p less than 0.0007). The highest DNA content of single nuclei ranged from 9.0-18.0 picograms (pg) (DI 2.9-6.03) in KA and 14.8-38.6 pg (DI 4.0-11.03) in SCC. The highest DNA content discriminated KA from SCC in 16 of 22 cases (p less than 0.003). In fresh frozen tissue touch preparations from 15 of the same lesions, there was considerable overlap in DNA indices of KA (0.534-1.39) and SCC (0.464-1.41). Abnormal DNA peaks seen in histograms from three SCC in paraffin embedded tissue sections were lost in the touch preparation histograms, probably due to inadequate sampling. Therefore, image analysis of paraffin-embedded tissue sections is better able to distinguish KA from SCC than touch preparations. PMID- 1875049 TI - Basal cell glycoprotein in pig epidermis closely resembles the beta 1 subunit of the integrin family of cell adhesion molecules. AB - A 135-kD conA-binding glycoprotein isolated from pig epidermis was previously localized to the surface of basal cells in stratified epithelia using affinity purified antibodies. Preembedding immunoperoxidase electron microscopy has now shown that this glycoprotein is concentrated on the lateral surfaces of basal cells but is not detectable on those surfaces adjacent to the basement membrane indicating a role in cell-cell rather than cell-substrate interactions. The basal cell glycoprotein was shown to resemble the beta 1 subunit of the integrin family following the generation of a specific monoclonal antibody (M5.25). The epidermal glycoprotein recognized by M5.25 and by antibodies against the beta 1 fibronectin receptor from human placenta co-migrated on SDS gels under both reducing and non reducing conditions. Its response to disulphide reducing agents was characteristic of beta 1 integrin subunits. In addition, the basal cell glycoprotein was shown to bind to the 120-kD cell-binding fragment of fibronectin in a RGD-dependent manner. It was readily detected by immunoblotting whole cell lysates of cultured pig keratinocytes suggesting increased expression in cultured cells compared to fresh epithelial tissue. The results suggest that beta 1 integrin subunits may be involved in cell-cell interactions between basal keratinocytes in pig epidermis and that these receptors are lost from the cell surface during terminal differentiation. Thus modulation of beta 1 integrin subunit expression may play an important role in regulating differentiation in pig epidermis. PMID- 1875050 TI - Quantitative determination of IL-1 alpha-induced IL-8 mRNA levels in cultured human keratinocytes, dermal fibroblasts, endothelial cells, and monocytes. AB - The presence of the leukocyte chemotactic cytokine interleukin 8 (IL-8) in psoriatic scales and in epidermal tissue overlying allergic patch test reactions suggests a role for this cytokine in certain inflammatory skin diseases. IL-8 can be produced by several cell types present in the skin. Their relative potentials for IL-8 expression has, however, not yet been studied, due to the lack of convenient methods for quantitative comparison of specific mRNA amounts in different cell types. Using a new method for quantification, we compared specific IL-8 mRNA amounts in cultures of keratinocytes, dermal fibroblasts, endothelial cells, and monocytes, stimulated with interleukin 1 alpha (IL-1 alpha). Endothelial cells produced very high, fibroblasts and monocytes intermediate, and keratinocytes low amounts of IL-8 mRNA. We also studied the time course of IL-8 mRNA levels in the four cell types following IL-1 alpha stimulation, and found a clear difference both in onset and stability of the response. We discuss the different strength of the response at different time points in the cell types analyzed in relation to their possible role in regulation of the normal response to stimulation. PMID- 1875051 TI - Blood mononuclear cells from patients with psoriasis exhibit an enhanced adherence to cultured vascular endothelium. AB - Blood mononuclear cells (MNC) from patients with psoriasis were more adherent to monolayers of endothelial cells prepared from human umbilical cord vein than otherwise similar cells from control subjects. This increase in adherence occurred in the presence (mean 37% increase; p less than 0.01) and absence (mean 47% increase; p less than 0.05) of 10% autologous serum and was not related to the disease severity of the patients. The augmented adhesiveness of the patients' cells was also apparent when using monolayers of endothelial cells isolated from human skin. The levels of immune complexes, complement, alpha 2-macroglobulin, acute phase proteins (alpha 1-acid glycoprotein, C-reactive protein and alpha 1 antitrypsin), and tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), and interleukin-1 beta (IL-1 beta) in the patients' sera were within normal limits. When MNC were added to endothelial monolayers that had been incubated with either TNF alpha or the highest concentration of rIL-1 beta used in the study, both the patients' and control's cells exhibited a similar increase in attachment (p less than 0.01). Pretreatment of endothelium with interferon gamma did not enhance the attachment of MNC from either group of subjects. The augmented adherence of the patient's MNC appears to be due to an abnormal adhesiveness of the lymphocytes rather than the monocytes and is not related to an enhanced expression of the cell-surface adhesion molecules CD11a/CD18. It is likely that the circulating MNC of psoriatic patients may be predisposed for extravasation into skin. PMID- 1875052 TI - Cyclic AMP-receptor protein activity in rat preputial cells. AB - Cells from the rat preputial gland--a type of sebaceous gland--exhibited specific responsiveness of cyclic 3',5'-adenosine monophosphate (AMP) dependent protein kinase to stimulation by agents that elevate intracellular cyclic AMP. Electron microscopy shows that the rat preputial gland resembles the human sebaceous gland, not only in terms of containing a sebocyte-like population of cells in an acinar arrangement at different maturational stages, but also in the morphology of its organelles such as abundant and sometimes atypical mitochondria, many perinuclear lysosomes with crystalline inclusions, lipid droplets of various sizes, and peroxisomes. Other cell types, among them duct and inflammatory cells, were evident in the tissue sections, but constituted a minor component. Responses to stimulation of the adenylate cyclase-protein kinase pathways were determined using preputial cells that had been both freshly dispersed and grown in monolayer culture. Stimulation with isoproterenol (IPR) or forskolin (FS) resulted in both cases in an increase of cyclic AMP binding of the regulatory (R) subunits of cyclic AMP-dependent protein kinase, as determined by photoaffinity labeling of R subunits with an azido analog of cyclic AMP ([32P]-8-azido cyclic AMP). Cells from the epidermis under comparable conditions responded to a lesser degree and with a different distribution of R subunit isoforms. There are, therefore, differences in receptor activity as well as in the transduction pathways between the two types of epithelial cell populations. These results indicate that the preputial gland contains precursor cells that differentiate in culture to retain specific molecular mechanisms of action mediated via cyclic AMP. PMID- 1875053 TI - Selective inactivation of human neutrophil elastase by synthetic tannin. AB - Tannins of natural or synthetic origin are well-known adjuvants in topical anti inflammatory therapy of skin diseases. In this study, the influence of synthetic tannin on neutrophil accumulation, enzyme release, and on the proinflammatory activity of neutrophil-derived enzymes was investigated. The results show that synthetic tannin (Tamol) specifically inhibits the neutrophil serine protease human leukocyte elastase (HLE) in an irreversible manner with a half-maximal inhibitory concentration (IC50) of 0.3 microgram/ml. Exogenous protein partially abolished the tannin-dependent HLE inhibition (IC50 of Tamol at 1% protein concentration:1.0 microgram/ml). Synthetic tannin did not influence the activities of other neutrophil enzymes like Cathepsin G, beta-glucuronidase, and myeloperoxidase. The specificity of Tamol for HLE was further substantiated by the lack of inhibition of other serine proteases. Additionally, Tamol had no effect on f-met-leu-phe-induced neutrophil chemotaxis and did not alter enzyme degranulation of neutrophils in response to f-met-leu-phe and opsonized zymosan. We conclude from our results that the anti-inflammatory properties of synthetic tannin may at least in part be due to inactivation of the proinflammatory protease HLE. PMID- 1875054 TI - Minoxidil: inhibition of proliferation of keratinocytes in vitro. AB - Previous studies have suggested that minoxidil stimulates growth of keratinocytes, possibly in a manner similar to the action of epidermal growth factor. Using both a short-term assay, thymidine incorporation, and a longer term assay, cell counting, to assess proliferative growth, we tested the activity of minoxidil in human keratinocyte cultures grown in 0.1 mM Ca(++). Minoxidil failed to stimulate growth in these assays. At concentrations of 5-10 micrograms per ml, minoxidil showed half-maximal inhibition of both EGF- and placental extract stimulated thymidine incorporation. Minoxidil also inhibited proliferative growth in the presence or absence of placental extract. Direct measurement of the ability of minoxidil to compete for binding to the EGF receptor indicated that minoxidil probably does not bind to the EGF receptor. Minoxidil was not toxic, as keratinocytes continued to survive and grow, although at a slower rate, in the presence of minoxidil. PMID- 1875055 TI - Soluble interleukin-2 receptor levels in patients with dermatitis herpetiformis. AB - To determine the role of T-cell activation in dermatitis herpetiformis (DH), soluble IL-2R levels were measured by enzyme-linked immunosorbent assay (ELISA) in the sera of 30 patients with DH. Levels of this shed receptor are considered to be a measure of in vivo T-lymphocyte activation, and are elevated in the sera of many patients with inflammatory and immune-mediated diseases. Fifteen of the thirty (50%) patients with DH had elevated levels of soluble IL-2R compared to one of 31 (3%) healthy HLA-B8 or HLA-DR3 control subjects (p less than 0.00001) and one of 10 (10%) healthy non-HLA-B8/-DR3 subjects (p less than 0.0018). In addition, the mean soluble IL-2R level in the patients with DH (744 +/- 381 U/ml) was also significantly higher than that seen in 31 healthy HLA B8 or HLA DR3 individuals (388 +/- 160 U/ml, p = 0.0001) and 10 healthy non-HLA-B8/DR3 individuals (397 +/- 201 U/ml, p = 0.002). Only two of the 30 patients with DH had active skin lesions at the time of serum sampling, one of whom had elevated levels of IL-2R. Measurement of soluble IL-2R levels in sequential serum samples, available in four patients with DH at times of active and inactive skin disease, demonstrated a temporal association between soluble IL-2R level elevations and active skin disease in two patients and no association in two patients. In one patient a marked elevation in soluble IL-2R levels occurred with the onset of gastrointestinal symptoms, which decreased by 14% with institution of a gluten free diet. In order to determine if soluble IL-2R levels are related to the mucosal immune response, the IL-2R levels were compared to the level of IgA antibodies directed against the dietary antigen beta-lactoglobulin. Ten of eleven (91%) patients with circulating IgA anti-beta lactoglobulin antibodies were also found to have elevated levels of IL-2R. In contrast, in the patients with no detectable IgA anti-beta lactoglobulin antibodies, only four of 16 (25%) had elevated levels of IL-2R (p = 0.001). Because IL-2R levels are not related to activity of the skin disease in patients with DH but are associated with the presence of IgA antibodies against the dietary antigen beta-lactoglobulin, these results suggest that some of the T-cell activation commonly present in DH reflects an ongoing immune response in the gastrointestinal tract. PMID- 1875056 TI - Human keratinocytes adhere to two distinct heparin-binding synthetic peptides derived from fibronectin. AB - Fibronectin is present at the dermal-epidermal junction in normal skin and is increased in skin tissues in inflammatory diseases, skin cancers, and wound repair. The present studies focused on further characterizing the interaction between fibronectin and keratinocytes, specifically addressing whether human keratinocytes utilize multiple adhesion promoting sequences within fibronectin. Initially, direct cell-binding assays were utilized in which keratinocyte adhesion to plastic substrata coated with fibronectin or proteolytic fragments of fibronectin was quantified. Intact fibronectin, a 75-kD proteolytic fragment containing the RGD sequence, and 33/66-kD cell adhesion/heparin binding fragments lacking the RGD sequence derived from the A and B chains of fibronectin, all promoted keratinocyte adhesion in a concentration-dependent manner. To further define putative cell-binding domains within the 33/66-kD fibronectin fragments, we studied three chemically synthesized peptides derived from the amino acid sequence of the 33-kD fragment of the fibronectin A chain: FN-C/H-I (YEKPGSPPREVVPRPRPGV), FN-C/H-II (KNNQKSEPLIGRKKT), and CS1 (DELPQLVTLPHPNLHGPEILDVPST). Substrata coated with either FN-C/H-I or FN-C/H-II promoted keratinocyte adhesion in a concentration-dependent and saturable manner, whereas peptide CS1 promoted no significant keratinocyte adhesion. In solution, both exogenous FN-C/H-I and FN-C/H-II partially inhibited keratinocyte adhesion to the 33/66-kD fibronectin fragments. Furthermore, antibodies prepared against these peptides also inhibited keratinocyte adhesion to the 33/66-kD fibronectin fragments. These data indicate that keratinocyte adhesion to fibronectin is mediated by multiple distinct amino acid sequences, at least two of which are localized to the carboxy-terminal heparin binding domain of fibronectin. PMID- 1875057 TI - Collagen telopeptides (cross-linking sites) play a role in collagen gel lattice contraction. AB - Solubilized interstitial collagens will form a fibrillar, gel-like lattice when brought to physiologic conditions. In the presence of human dermal fibroblasts the collagen lattice will contract. The rate of contraction can be determined by computer-assisted planemetry. The mechanisms involved in contraction are as yet unknown. Using this system it was found that the rate of contraction was markedly decreased when collagen lacking telopeptides was substituted for native collagen. Histidinohydroxylysinonorleucine (HHL) is a major stable trifunctional collagen cross-link in mature skin that involves a carboxyl terminal, telopeptide site 16c, the sixteenth amino acid residue from the carboxy terminal of the telopeptide region of alpha 1 (I) in type I collagen. Little, if any, HHL was present in native, purified, reconstituted, soluble collagen fibrils from 1% acetic acid-extracted 2-year-old bovine skin. In contrast, HHL cross-links were present (0.22 moles of cross-link per mole of collagen) in lattices of the same collagen contracted by fibroblasts. However, rat tail tendon does not contain HHL cross-links, and collagen lattices made of rat tail tendon collagen are capable of contraction. This suggests that telopeptide sites, and not mature HHL cross links per se, are essential for fibroblasts to contract collagen lattices. Beta aminopropionitrile fumarate (BAPN), a potent lathyrogen that perturbs collagen cross-linking by inhibition of lysyl oxidase, also inhibited the rate of lattice cell contraction in lattices composed of native collagen. However, the concentrations of BAPN that were necessary to inhibit the contraction of collagen lattices also inhibited fibroblast growth suggestive of cellular toxicity. In accordance with other studies, we found no inhibition of the rate of lattice contraction when fibronectin-depleted serum was used. Electron microscopy of contracted gels revealed typical collagen fibers with a characteristic axial periodicity. The data provide evidence that collagen telopeptide sites play a role in collagen gel lattice contraction. PMID- 1875058 TI - Expression and secretion of leukocyte chemotactic cytokines by normal human melanocytes and melanoma cells. AB - The capacity of human melanocytes and melanoma cells to produce IL-8 and monocyte chemotactic and activating factor (MCAF) was investigated. Melanocytes expressed mRNA for IL-8 and MCAF, when stimulated with either IL-1 alpha or TNF alpha, but not when stimulated with IL-6, IFN gamma, or LPS alone. IL-8 and MCAF could be induced in a dose-dependent fashion with doses as low as 0.1 ng/ml TNF alpha and 0.5 ng/ml IL-1 alpha. IL-8 and MCAF mRNA were rapidly expressed and peaked between 2 and 4 h for IL-8 and between 4 and 8 h for MCAF. This correlated well with the accumulation of IL-8 antigen as measured by a radioimmunoassay. Supernatants from melanocyte cultures stimulated with either IL-1 alpha or TNF alpha and separated on a heparin-Sepharose column became positive for neutrophil and monocyte chemotactic activity in a dose- and time-dependent fashion. When IFN gamma was added to melanocyte cultures stimulated with suboptimal doses of TNF alpha there was a synergistic increase in secreted IL-8 protein and monocyte chemotactic activity. These data provide further evidence for the possible role of melanocytes in the initiation of an inflammatory reaction. Three different malignant melanoma cell lines stimulated with either TNF alpha or IL-1 alpha expressed IL-8 mRNA, but not mRNA for MCAF. The IL-8 mRNA signal corresponded well with the amount of secreted IL-8 protein. These data suggest that IL-8 and MCAF may play a role in growth regulation and spreading of melanomas. PMID- 1875059 TI - Ultraviolet light-induced augmentation of SS-A/Ro. PMID- 1875060 TI - Autoreactive proliferative responses by T-cell lines isolated from psoriatic lesions. PMID- 1875061 TI - NAP-1/IL-8 immunoreactivity in normal and psoriatic skin. PMID- 1875062 TI - Successful treatment of Taenia saginata and Hymenolepis nana by single oral dose of praziquantel. AB - Infections by adult cestodes are widely distributed in the world, and induced digestive and general disturbances. In this study, 40 patients with Taenia saginata and 15 with Hymenolepis nana were treated by one single oral dose of Praziquantel, at the dosage of 10 mg/kg/day and 20 mg/kg/day respectively. As side effects, no biological disturbances occurred, but 6 patients complained of abdominal pain and diarrhea. The efficiency was complete. Praziquantel, a wide spectrum anti-helminthic day drug, used in schistosomiasis, fascioliasis, cysticercosis, is the best treatment of adult cestodes. PMID- 1875063 TI - Parasitic infections associated with mental retardation in Egypt. AB - Examination of 150 mentally retarded patients for parasitic infections by urine and stool analysis revealed that 115 (76.67%) were positive. The most prevalent parasites found were T. trichiura in 56%, A. lumbricoides in 40.6% and A. duodenale in 21.33%. Double infection was present in 30.67%, triple infection in 15.33% and quadriple infection in 6%. Eosinophilia was detected in 91 (64.08%) of 142 examined cases, all were suffering from intestinal parasites. S. stercoralis was present in 11.33% by stool examination and culture and in 24 (60%) out of 40 examined cases by the IFAT. Toxocara antibodies were present in 38 (56.72%) out of 67 examined cases by the IFAT. Toxoplasma antibodies were present in 106 (74.65%) out of 142 examined cases by the IFAT. PMID- 1875064 TI - A case of ectopic fascioliasis in a farmer from Mansoura City, Dakahlia, Egypt. AB - Human fascioliasis is a new parasitic health problem in Egypt. This paper reports a case of ectopic fascioliasis in the right side of the pleural cavity of a farmer. PMID- 1875065 TI - Leishmania major and Meriones crassus in North Sinai Governorate, Egypt. AB - Zoonotic cutaneous leishmaniasis (ZCL.) now seems to be more than was once thought in North Sinai. In the present study, Meriones crassus (23) and M. sacramenti (10) were collected from limited foci of human CL. Leishmania major (four strains) were isolated from M. crassus as indicated enzymologically by the cellulose acetate electrophoresis of nine different enzymes (MDH, 6 PGD, GD, PK, PGM, NH, GPI, ME and SOD). The four strains were equivalent to zymodeme LON 1 (three strains) and LON 2 (one strain). PMID- 1875066 TI - Some immunological aspects of chronic liver diseases in Egyptian children. AB - This study was conducted on 40 Egyptian children (21 males and 19 females) with various chronic liver diseases, selected from the out-patient Pediatric Hepatology Clinic of Ain Shams University Hospital. Their ages ranged from 1.5 to 13 years with a mean of 5.98 +/- 3.72 years. Twenty healthy children of comparable age and sex to the patients were chosen as controls. All children were subjected to detailed history taking, thorough clinical examination and laboratory investigations including full blood picture, urine and stool examination, liver function tests, prothrombin time and hepatitis B surface antigen in addition to sigmoidoscopy with rectal snip examination, abdominal ultrasonography and liver biopsy. Moreover, immunological investigations were done, that included estimation of the serum complement levels of C3 and C4 by using single radial immunodiffusion method, assessment of the phagocytic and intracellular killing activity of polymorphonuclear leucocytes by living Candida albicans uptake and detection of non organ specific autoantibodies in the serum by indirect immunofluorescence technique. This study showed that the serum level of C3 was increased and C4 was decreased significantly in patients with chronic liver disease, especially in chronic active hepatitis. Regarding phagocytosis, there was significant impairment of the neutrophil phagocytic function but not the intracellular lytic activity of candida albicans. This reduced phagocytic function was more pronounced in patients having chronic hepatitis and cirrhosis than in bilharzial and other cases. Serum autoantibodies; antinuclear and antimitochondrial antibodies were absent in the sera of both patients and controls, while antismooth muscle antibodies were found in the sera of 47.5% of patients with chronic liver diseases and non of the control sera. The highest incidence of these antibodies was present in HBs Ag negative patients with chronic active hepatitis (80%). We concluded that patients with chronic liver diseases have disturbed functions of both complement and phagocytic systems that may lead to increased susceptibility to recurrent infections. So, routine assessment of immunological status with early diagnosis and treatment of infections are important in the proper management of these patients. In addition, detection of serum auto-antibodies in these patients is helpful in the early diagnosis of auto-immune liver diseases. PMID- 1875067 TI - Prevalence of congenital and acquired toxoplasmic uveitis as evidenced by two serologic methods. AB - Anti Toxoplasma antibodies were sought in 34 patients with uveitis and 20 healthy individuals by IHAT and IFAT. The total sero-positivity rate was 26.5%. The prevalence was significantly higher among patients with posterior (42.9%) than with anterior uveitis (7.1%) and control (10%) indicating significant role of Toxoplasma as an aetiologic agent of posterior uveitis. 14.4% of patients with seropositive uveitis were considered to be due to primarily acquired Toxoplasma infection as evidenced by their significant higher IFAT mean titre (576.7 +/- 322.1) than IHAT (48 +/- 18.5). The reported toxoplasmic anterior uveitis case is most probably secondary to posterior involvement. PMID- 1875068 TI - Causes of lymphadenopathy in Egyptian children other than malignancy. AB - Fifty children aged 3 to 12 years presented with cervical or inguinal lymph nodes enlargement were selected from Zagazig University Hospitals. They were subjected to routine laboratory examination as well as histopathological & immunopathological studies. The results revealed eosinophilia and intestinal parasites in 80 percent. Besides, pediculosis and flea dermatitis were also demonstrated in 30 and 12 percent respectively. Histopathological studies of the nodal tissues revealed sinus hyperplasia (ten cases), reactive paracortical hyperplasia (30 cases) and necrosis and caseition (ten cases). Infiltration with eosinophils was demonstrated in the nodal tissues of 40 cases. Immunopathologyical studies revealed cytotoxic T-cells in all the cases, and helper T lymphocytes in only 15 cases. It is concluded that this may give an explanation of some causes of lymphadenopathy in Egyptian children other than malignancy. PMID- 1875069 TI - Detection of antitrichomonal antibodies in sera and cervical secretions in trichomoniasis. AB - The AT, IFAT and ELISA were used to detect circulating and cervical antitrichomonal antibodies, using living and dead whole parasite or soluble protein extract as antigens respectively, in 93 women with proven trichomoniasis and 25 healthy women as controls. The results revealed that the IFA test is the most sensitive one for detecting serum (92.5%) and cervical (87.1%) antibodies. Circulating IgM rather than IgG appeared to be the antibody class involved in infected women, while cervical secretions showed a significant high concentrations of IgA, IgG and IgM. On the other hand, no IgE was detected neither in sera nor in secretions. The detection of antitrichomonal antibodies in controls, with no demonstrable trichomonal infection, may be accounted for previous infection. PMID- 1875070 TI - Effect of certain formulations of the bacterial larvicide, Bacillus thuringiensis, serotype H-14 on Culex pipiens L. in Egypt. PMID- 1875071 TI - Testicular changes in rats after Trichinella spiralis infection. AB - Infection of rats with Trichinella spiralis was found to be associated with testicular enlargement. A paucity of Leydig cells with marked oedema of interstitial areas were observed. Most of the seminiferous tubules were lined by spermatogonia and primary spermatocytes. T. spiralis larvae were not detected in the testes. Using the indirect immunoperoxidase procedure, T. spiralis antigen was detected as weak brown staining. The antigen was diffusely distributed in the cytoplasm of spermatogenic cells, Sertoli cells and focally around the tubular basement membrane of the infected rats. The significance of the results was discussed. PMID- 1875072 TI - Experimental trichinosis: effect of immunosuppression on the host-parasite system. AB - Experimental trichinosis in immunocompetent verus immunosuppressed albino rats was studied over a period of two months. The immunosuppressed ones showed significant delay in expulsion of adult worms, significant increase in the yield of muscle larvae, lower IFA titres and delayed encystation of muscle larvae with mild cellular infiltration. Specific antigen deposits detected in the muscles and different tissues of the immunosuppressed rats indicated augmentation of circulating antigens. In both groups, the liver, kidney, lung, brain and testes showed nonspecific pathological changes but larvae were never detected in examined sections. Incidentally, on the 14th post-infection day, two immunocompetent rats were found pregnant, and near-full-term embryos showed more deposition of Trichinella antigens in most of their tissues indicating placental passage of circulating antigens. This study indicates that in patients receiving immunosuppressive drugs, possible exposure to T. spiralis infection will result in severe manifestations or complications. PMID- 1875073 TI - Length and hatchability of Schistosoma mansoni eggs. AB - Mature Schistosoma mansoni eggs, purely isolated from the intestines of infected mice, were allowed to hatch and classified microscopically according to their lengths. The hatching percentage and the type of shell rupture were studied. An inverse relationship between the length and hatchability of eggs was proved. Smaller eggs have a high hatchability percentage, while eggs larger than 160 um in length failed to hatch. The predominance of oblique type of tear in the shells after rupture suggests a longitudinal arrangement of egg shell chemical constituents. PMID- 1875074 TI - Effect of laval breeding conditions on the morphological, ovarian and behavioral characteristics of Anopheles pharoensis of the emerged females. AB - Under laboratory conditions, morphological, ovarian and behavioral characteristics of Anopheles pharoensis females were found to be affected by a combination of 3 larval environmental factors: quantity of food, density of larvae and salinity of the rearing medium. Size and weight of the emerged females were decreased by lowering the quantity of food (basic ration), increasing the population density of larvae (200 larvae/pan) and increasing the salinity of the rearing medium (1/5 dilution of Sea water). Embryogenesis and behavior of the female were also affected by the larval environmental factors; the female emerged with the undeveloped stag of the ovaries (Christophers's stage I), needs a multiple feeding with 2 blood meals required, at times, to reach the gravid stage and produce the first batch of eggs. The female emerged with fewer number of ovarian follicles and thus affecting the number of produced eggs. The emerged female takes as maximum 4 blood meals to lay 3 batches of eggs during the life cycle (8 days). PMID- 1875075 TI - Capillaria hepatica: an experimental study of infection in white mice. AB - C. hepatica were found in 15.8% of wild caught rats. Experimental studies showed that the host reaction started specifically against developing worm as early as the 9th day post infection. Eggs started to develop inside uterus in the 3rd week P.I. The second month of infection was the maximum growth and activity of worm, egglying, severe liver destruction and necrosis, degeneration, granuloma formation as well as the greatest humoral and cellular responses of the host. By the third month P.I., there was a gradual increase of the fibroblastic activity around the already formed granuloma and a decrease of antibody level in peripheral blood. Areas of hepatic regeneration started between the fibrotic granulomas and the liver enzymatic reactions returned gradually to their normal levels. Viable eggs were seen until the eighth month of infection free or surrounded by fibrous tissue. PMID- 1875076 TI - An assessment of hepatic functional capacities and haemoglobin values in amaebiasis. AB - Fourty adult males with amaebiasis and a match control group of the same age and sex were subjected to complete blood examination. The results showed that the mean values for total serum protein, total serum bilirubin, A.L.P. and Hb % were within the acceptable limits i.e. statistically insignificant, whilst A.S.T. and A.L.T. were not within the acceptable limits, i.e. statistically significant. The percentages of normals as regards the frequency distribution test were as follows: Total serum protein (80%), total serum bilirubin (82.5%), A.L.P. (94.59%), A.S.T. (67.5%), A.L.T. (75%) and Hb. (86.21%). The regression analysis test, confirmed by the correlation test, were performed to indicate the relationship between the intensity of infection (indicated by the population of E. histolytica in stool analysis) and the serum levels of the tests to follow. Accordingly the serum levels of A.L.P., A.S.T. and A.L.T. showed a relatively slight increase, while the total serum protein level and Hb% showed a slight decrease. The serum bilirubin indicated no change whatsoever. PMID- 1875077 TI - Evaluation of the antiparasitic effect of aqueous garlic (Allium sativum) extract in hymenolepiasis nana and giardiasis. AB - The effect of serial dilutions of crude garlic (Allium sativum) extract on adult Hymenolepis nana was studied to detect the minimal lethal concentration which was found to be 1/20. A. sativum was tried in the treatment of 10 children infected with H. nana and 26 infected with G. lamblia as 5 ml crude extract in 100 ml water in 2 doses per day, or commercial preparation (0.6 mg capsules) 2 capsules twice/day for 3 days. A sativum was found to be efficient, safe and shortens the duration of treatment. The possible mode of action of A. sativum and the correlation between the clinical and parasitological findings were discussed. PMID- 1875078 TI - Some myiasis producers in Cairo and Giza abattoirs. AB - The most important insects from medical point of view, are the blood suckers or the insect-borne diseases. Still others, almost non-blood suckers, but may attack man and animal to deposit their eggs or larvae causing pathogenic condition known as myiasis. In the present paper, a total of nine myiasis producing dipterous flies were collected from Cairo and Giza abattoirs. They were: Musca d. vicina, Calliphora vicina, Chrysomyia albiceps, C. marginalis, Lucilia sericata, L. cuprina, Sarcophaga haemorrhoidalis, Wohlfahrtia magnifica and Oestrus ovis. Their role as myiasis producers in man and animal was discussed. PMID- 1875079 TI - Toxoplasma antibodies in patients with meningoencephalitis. AB - This study was carried on 42 patients with meningoencephalitis who had negative C.S.F. cultures for common pathogenic bacteria. The percentage of seropositive Toxoplasma antibodies (IgG) using Indirect Immuno Fluorescent Assay was 10/42 (26%). The clinical presentation and C.S.F. changes with high antibody titres were encountered. The results may incriminate toxoplasmosis as an etiologic agent for meningoencephalitis. PMID- 1875080 TI - Human fascioliasis: a parasitic health problem in Dakahlia Governorate, Egypt. AB - Fascioliasis has a cosmopolitan distribution and is prevalent in sheep-raising countries. Now, it is an increasingly important parasite of man in the Mediterranean countries. In Dakahlia G., human fascioliasis has imposed itself as a parasitic health problem. In this paper, 23 human cases were selected to throw some light on the signs, symptoms and diagnosis of the disease. It was concluded that painful hepatomegaly, fever, anaemia and marked eosinophilia are tetrad suggesting fascioliasis in patient who has consumed watercress as green salade. Data concerning treatment and follow up will be published later. PMID- 1875081 TI - Hepatitis D anti-bodies in some HBs Ag positive in Saudis at Riyadh. AB - This study was done on 212 male and female Saudi blood donors and those visiting the Outpatient Clinics in Al Ali General Hospital during the years 1987 to 1990. None of them had history of hepatitis and all were clinically free. The prevalence of anti-Delta Ab in hepatitis B surface antigen (HBs Ag) carriers was 17.6%. The existence of closely linked family ties and joint family systems, result in close contact between patients and other members of the family and hence the high prevalence rate in normal population (8%). Vaccination against Hepatitis B virus may be particularly necessary. PMID- 1875082 TI - Toxocara canis antibodies by counter immuno-electrophoresis. AB - Counter immunoelectrophoresis was used for anti-toxocaral antibodies in mice experimentally infected with Toxocara canis using adult worm antigen. The test seems to be valuable and gives good information about the infected rate. PMID- 1875083 TI - Parasitic infection in Sennores primary school, El-Fayum Governorate, Egypt. AB - Sennores Center has not been examined for parasitosis. In this paper, a total of 252 pupils in Sennores primary school were examined. The commonest parasite was S. haematobium (29.4%) and the least common was T. saginata (1.2%). Single infection was in 50.4% and double infection was in 40.1%. One case showed triple infection. The whole results were discussed. PMID- 1875084 TI - Effect of nutritive elements on the extracellular protein of different Bacillus strains, toxic to mosquito larvae. AB - The effect of 5 nutritional elements (glucose, peptone, yeast extract, beef extract and lactic acid) on the growth of the 4 tested Bacillus strains (Bacillus thuringiensis Bactimos 78, B. thuringiensis IPS 82, B. sphaericus Solvay 85 and B. sphaericus Rb 80) as well as on the concentration of their extracellular proteins were studied. The nutritive elements were individually tested either dissolved in distilled water or in a buffer base. Results indicated that the bacterial growth was higher when the nutritive elements were dissolved in a buffer base than in dist. water. The concentration of the extracellular proteins were always higher in the absence of the inorganic minerals, although the toxicity of these extracellular proteins against 3rd instar Culex pipiens larvae increased in the presence of these inorganic elements. PMID- 1875085 TI - Trichinosis in camels. PMID- 1875086 TI - A case of chloroquine resistant Falciparum malaria in Saudi Arabia. PMID- 1875087 TI - Generalized pediculosis due to Phthirus pubis. PMID- 1875088 TI - A case of urinary myiasis due to Piophila casei. PMID- 1875089 TI - [Observation of biological macromolecules by scanning electron microscopy]. PMID- 1875090 TI - [Macrophage scavenger receptors: the membrane glycoproteins mediating endocytosis of denatured or modified substances]. PMID- 1875091 TI - [Synchrotron radiation and structural kinetics]. PMID- 1875092 TI - [Beginning and the rate of aging: is there an aging gene?]. PMID- 1875093 TI - [Production of magnetic material by magnetic bacteria]. PMID- 1875094 TI - [Epidermosides--epidermal acylsphingoglycolipids and their barrier function]. PMID- 1875095 TI - [The use of dimethyl sulfoxide (DMSO) for protein fractionation]. PMID- 1875096 TI - A general solution of the problem of mixing of subpopulations and its application to risk- and age-structured epidemic models for the spread of AIDS. AB - A central aspect in the study of the dynamics of sexually transmitted diseases is that of mixing. The study of the effects of social structure in disease dynamics has received considerable attention over the last few years as a result of the AIDS epidemic. In this paper, we formulate a generalization of the Blythe and Castillo-Chavez social/sexual framework for human interactions through the incorporation of age structure, and derive an explicit expression in terms of a preference function for the general solution to this formulation. We emphasize the role played by proportionate mixing, the only separable solution to this mixing framework, through the discussion of several specific cases, and we formulate an age-structured epidemic model for a single sexually active homosexual population, stratified by risk and age, with arbitrary risk- and age dependent mixing as well as variable infectivity. In the special case of proportionate mixing in age and risk, an explicit expression for the basic reproductive number is computed. PMID- 1875097 TI - Modelling and numerical optimization of corneal rotation. AB - Rotational ipsilateral penetrating autokeratoplasty can be performed for patients whose vision is impaired by corneal opacities overlying the pupil and where an adequate area of clear peripheral cornea is present. A method is presented for determining the maximum clear central corneal area that can be obtained by rotational autokeratoplasty and the most appropriate trephine size and placement. The mathematical modelling consists of estimating the shape of the opacity perimeter using nonlinear constrained optimization. PMID- 1875098 TI - [Recent advance on clinical study of pneumonia]. PMID- 1875099 TI - [Pneumonia and changes in pathogenic bacteria]. PMID- 1875100 TI - [Compromised host and pneumonia]. PMID- 1875101 TI - [Image diagnosis of pneumonia]. PMID- 1875102 TI - [Diagnosis and therapy of mycoplasma and viral pneumonia]. PMID- 1875103 TI - [Diagnosis and therapy of Chlamydia pneumonia]. PMID- 1875104 TI - [Diagnosis and therapy of fungal lung diseases]. PMID- 1875105 TI - [Diagnosis and therapy of parasitic lung diseases]. PMID- 1875106 TI - [Diagnosis and therapy of pneumonia caused by drug-resistant strains of bacteria]. PMID- 1875107 TI - [Respiratory tract diseases and infections]. PMID- 1875108 TI - [Pneumonia in the elderly]. PMID- 1875109 TI - [Therapy of pneumonia caused by unknown pathogens]. PMID- 1875110 TI - [Therapy of outpatients with respiratory tract infections]. PMID- 1875111 TI - [A case of retroperitoneal hemorrhage due to multiple myeloma complicated with factor X deficiency and amyloidosis]. PMID- 1875112 TI - [A case of myelodysplastic syndrome with abnormal chromosome t (3;4), proliferation of megakaryocytes and myelofibrosis, transition to overt leukemia]. PMID- 1875113 TI - [A case of Weber-Christian disease associated with cytophagic histiocytosis and pancytopenia]. PMID- 1875114 TI - [A case of chronic myeloid leukemia with cytogenetic remission and disappearance of Ph1 positive cells due to interferon-alpha administration]. PMID- 1875115 TI - [Cytokines]. PMID- 1875116 TI - Posterior approach to the rectum for treatment of selected benign lesions. AB - Access to lesions in the mid-rectum can be difficult. This report summarizes our experience with a posterior approach to the rectum in 22 men and 13 women, age range 21 to 96 years. Surgical indications included villous tumours, rectal prolapse, rectal strictures or rectal fistulae. No postoperative complications were observed in 20 patients, but fistulae developed in seven patients, of whom three required proximal colostomy and surgical treatment. Four healed spontaneously. Two patients developed sacrococcygeal hernia. Pathologic examination of villous tumour showed extensive malignant change in three cases requiring rectal resection with end-to-end colo-anal anastomosis. In two patients mild incontinence developed, treated by biofeedback. Residual peri-anal pain was reported by two patients. The posterior approach to the rectum is particularly useful for benign lesions too high for a transanal resection and too low for a transabdominal resection. PMID- 1875117 TI - Radiological study of changes in the pelvis in women following proctocolectomy. AB - The vagina, uterus and adnexa of 21 women who had a proctocolectomy for ulcerative colitis or Crohn's colitis were examined with vaginography and hysterosalpinography. Six healthy women were used as controls. A characteristic post-operative deformation of the adnexa and the vagina was demonstrated. In 17 of 21 women the fallopian tube anatomy was pathological, in four cases with total obstruction. These abnormalities explain why vaginal discharge, dyspareunia and involuntary sterility are common complaints in women after this type of surgery. PMID- 1875118 TI - Alterations in anorectal function after anterior resection for cancer of the rectum. AB - We have evaluated by means of a clinical and functional study the alterations in anorectal function of a group of 50 consecutive patients who have undergone an anterior resection of the rectum. Results are correlated with the anastomosis location and the time passed after the operation. According to research data this operation changes the patient's defaecation habits and the manometric and radiological parameters of anorectal function. These alterations are more evident in patients with a low anastomosis. The qualitative characteristics of defaecation did not change significantly in relation to the time passed since operation. However, there was a significant increase in compliance 6 months after operation, and the threshold rectal volume and the maximum tolerated volume also showed a significant increase 12 months following operation. PMID- 1875119 TI - Simultaneous resection of colorectal carcinoma and synchronous liver metastases in a district hospital. AB - Of 491 patients operated for carcinomas of the colon or rectum between 1984 and 1989, 106 were tumour stage IV, U.I.C.C.(Dukes' 'D') at time of operation. In 22 of these cases a radical resection of the carcinoma of the colon or rectum and of synchronous liver metastases was performed simultaneously. In 20 patients the metastases were confined to one, in two they were found in both hepatic lobes. In one case a solitary metastasis of the lower lobe of the right lung was resected additionally. Three right-sided hemihepatectomies, one extended right hemihepatectomy, five left-sided hemihepatectomies, three left-sided lateral segmentectomies, seven atypical segmental resections and three wedge resections were performed. The mean operation time for the radical resection of the carcinomas of the colon or rectum as well as of the liver metastases was 3.5 (3 5.2)hours. An average of 3 (0-9) blood units were needed intraoperatively. The major liver resections were performed in complete normothermic vascular ischaemia using the finger fracture method. The time of ischaemia ranged between 8 and 25 min. Only 1 of 22 patients died postoperatively (30 days postoperative hospital mortality rate 4.5%). Five of 17 patients were free of tumour 2 years after operation. Eight of 22 were alive 2 years after operation (non-age corrected 2 year survival rate 36.4%), 2 of them are alive more than 5 years after treatment. Our results demonstrate that simultaneous resection of colon or rectum carcinoma and of synchronous (resectable) liver metastases can be performed successfully, even in a district hospital. PMID- 1875120 TI - Heterogeneity in ploidy and S-phase fraction in colorectal adenocarcinomas. AB - The heterogeneity in the DNA content was analysed in multiple biopsies from the surgical specimens in 77 cases of colonic and 46 cases of rectal adenocarcinomas. Frozen and unfixed tumour tissue was analysed with the flow cytometric technique. A total of 78/123 (63%) of all tumours displayed aneuploid stemlines in one or more pieces of tumour tissue; 45 were homogeneously aneuploid and 33 were heterogeneous, presenting both aneuploid and near-diploid samples. The remaining 45 tumours were homogeneously near-diploid. The heterogeneity in ploidy tended to be slightly higher if ten as compared with four samples from each tumour were analysed. Ploidy correlated to localization in the bowel and gender, but not to age, histopathological tumour stage, tumour differentiation or to the resectability rate for cure. The mean value of the S-phase fraction was 17% (range 7-31%) in the near-diploid and 14% (range 8-20%) in the aneuploid tumours. The range of the intratumoural variation was small for the DNA index (at most 5%) and high for the S-phase fraction (19% for near-diploid and 24% for aneuploid tumour pieces). Neither the mean value nor the heterogeneity in the DNA index and in the S-phase fraction displayed any correlation with the studied characteristics. In conclusion, the ploidy and the S-phase fraction varied considerably both within and between the tumours. As a consequence, multiple sampling is mandatory for a correct classification of colorectal adenocarcinomas based on the DNA content. PMID- 1875121 TI - Phospholipid profiles of human colon cancer using 31P magnetic resonance spectroscopy. AB - Phospholipids of 16 malignant and 11 non-malignant human colon specimens were analyzed using a chloroform-methanol analytical reagent in conjunction with 31P magnetic resonance spectroscopy (MRS) at 202.4 MHz. Sixteen individual generic phospholipids were identified and quantified for statistical intergroup comparisons. Statistically significant elevations in the relative concentrations of lysophosphatidylcholine and phosphatidylcholine plasmalogen were seen in malignant tissues along with significantly depressed levels of sphingomyelin and phosphatidylethanolamine plasmalogen. The malignant and non-malignant tissue groups were further differentiated by the detection of the minor phospholipids, lysophosphatidylcholine plasmalogen, lysophosphatidylethanolamine plasmalogen, lysophosphatidic acid and phosphatidylglycerol exclusively present in the malignant tissues and by significant changes in computed phospholipid metabolic indices that were dominated by choline containing lipids. The 31P MRS methods used represent an advancement over previous protocols for identifying and quantifying major and minor tissue phospholipids making this the first direct study of membrane phospholipids in human colon tissues using 31P MRS. The phospholipid profiles obtained may provide important information regarding the nature of the malignant cell's membrane system and identify markers which may be used to estimate malignant propensity, aggressiveness of disease and provide prognostic information. PMID- 1875122 TI - Metabolism of large bowel mucosa in health and disease. PMID- 1875123 TI - Curative local therapy of rectal cancer. PMID- 1875124 TI - Local curative treatment of rectal cancer. PMID- 1875125 TI - Minimal invasive surgery in the local treatment of rectal cancer. PMID- 1875126 TI - Endoscopic transanal resection for rectal cancer. PMID- 1875127 TI - Cancer of the rectum--local excision. PMID- 1875128 TI - Parasacral surgery for curative treatment of rectal cancer. PMID- 1875129 TI - Exteriorized colonic anastomosis. AB - The risk of anastomotic failure in the unprepared colon is generally high. Therefore, Hartmann's operation is frequently employed in emergencies. We present an alternative technique, the exteriorized anastomosis described until now only for cases of perforation. Exteriorized anastomosis was performed in 14 patients. The preoperative diagnosis was occlusive neoplasm, perforated diverticulitis or traumatic performation of the sigmoid colon. Four patients subsequently developed partial anastomotic dehiscence, but without the consequences of intraperitoneal dehiscence. We think that exteriorized anastomosis is a useful alternative in high risk situations. PMID- 1875130 TI - Secretory IgA- and IgG-coated bacteria in chronically discharging ears. AB - SIgA- and IgG-coated bacteria obtained from 17 discharging middle ears (14 patients, 9 male, 5 female, age range from 1 to 79 years) were evaluated using an immunofluorescence assay. Simultaneously, quantitative and qualitative bacteriological analyses of the middle ear effusions (MEEs) were performed. MEEs containing Staphylococcus aureus harboured bacteria which were intensely coated with both SIgA and IgG antibodies. In contrast, MEEs containing Pseudomonas aeruginosa displayed minimal, if any, SIgA- and IgG-coated bacteria. Two young patients harboured bacteria (Haemophilus influenzae and S. aureus/Streptococcus pneumoniae, respectively) which were heavily coated with IgG, but not with SIgA. Immunoglobulin-coating of bacteria involved in otitis media is of the utmost importance in eradication of the infection. PMID- 1875131 TI - Anatomy of the temporalis fascia. AB - The anatomy of the different layers of the temporalis fascia is reviewed. The superficial and deep layers of the temporalis fascia have been studied by light microscopy to assess any histological difference between the two. We have also assessed the physical characteristics of the different layers by measuring their Young's modulus in the wet and dry states. Anatomically the superficial layer is part of the epicranial aponeurosis and thus covers nearly the entire lateral aspect of the skull. The deep temporal fascial layer covers exactly the temporalis muscle and measures 10 x 12 cm. The fascial layers have a separate arterial and venous supply enabling them to be used as a homograft, a rotation flap or free microvascular flap. Histologically there is no difference between the two layers. A study of the physical characteristics of the two fascial layers using Young's modulus revealed no significant difference in elasticity between the two. The most significant factor affecting the elasticity was the state of hydration of the fascia. PMID- 1875132 TI - Management of retraction pockets of the pars tensa. AB - A study of 73 patients with retraction pockets of the pars tensa (93 affected ears) has been carried out. Of these 32 per cent had otalgia and 31 per cent reported episodes of aural discharge. Adequate audiometric data was available on 75 ears. Mean air-bone gaps were calculated using 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz. Thirty per cent of ears had air-bone gaps of less than 10 dB and in 93 per cent the air-bone gap was less than 30 dB. Air-bone gaps of more than 40 dB were found in seven per cent. Of this group, seven patients were selected for surgical treatment. In all cases the retraction pockets were elevated and averted. In six cases, the thinned tympanic membrane was reinforced with a composite graft of cartilage and perichondrium. This technique has also been used in three patients not included in this study group. An ossiculoplasty was performed in four cases. In the early months, the retraction pockets remained completely everted. However, by 12 months some degree of retraction had recurred in four of the six patients who have been followed for more than 12 months. PMID- 1875133 TI - Realities in ossiculoplasty. AB - The results of ossiculoplasty are frequently reported in terms of closure of the air-bone gap. This parameter is a reliable indicator of the degree of technical success, and is useful in comparing different materials and types of reconstructions. However, assessment of the operated ear alone does not evaluate the effect of surgery on binaural hearing ability, leading to the situation where sub-optimal advice may be given to patients pre-operatively. This article advocates a more patient orientated method of assessing the results of ossiculoplasty. Previous studies have indicated that the operated ear must reach an air conduction level of 30 dB for the speech frequencies, or be within 15 dB of the other ear, to ensure that the patient will gain significant benefit. A graphical method for the prediction of patient benefit is presented, and compared to the rule of thumb quoted above. The implications for surgeons and patients considering ossiculoplasty are obvious. Many statements routinely made to patients prior to surgery for conductive hearing loss are unduly optimistic and unrelated to the realities of reported results. There is a need to determine what types of such hearing losses can be helped surgically, and more importantly to what extent the patients hearing disability can be relieved. PMID- 1875134 TI - Characterization of severely and profoundly hearing impaired adults attending an audiology clinic. AB - Despite the fact that around 12 per cent of adult patients attending an audiology department will be severely hearing impaired (pure tone averages of 0.5, 1, 2 and 4 kHz of 70 dB HL or worse in the better hearing ear), their clinical and audiometric characteristics have not been well documented. These characteristics were collected prospectively in 132 adult patients attending a Severe Impairment Clinic, set up to manage their specific problems. The inability to provide sufficient masking makes audiometric assessment of the severity of the impairment uncertain in the poorer hearing ear in 52 per cent of these patients. In addition, the limited bone conduction output makes it almost invariably impossible to assess the masked bone conduction thresholds and hence the air-bone gap in the poorer ear. Hence, accurate characterization is only practical of the better hearing ear in such patients. In 67 per cent of the better hearing ears, there was a mixed hearing impairment, the air-bone gap being 20 dB or greater. The aetiology of the conductive component was almost equally otosclerosis and chronic otitis media. In only 19 per cent was the impairment of a pure sensorineural type, broken down as 6 per cent congenitally acquired, 5 per cent due to meningitis and 9 per cent being adult in onset. In the remaining 14 per cent of patients the type of impairment could not be classified as the bone conductive thresholds were off scale. Having had experience of managing these patients at a special clinic and knowing the workload involved, it is argued that consideration be given to setting up such clinics in most departments. PMID- 1875135 TI - Effect of nasal packing on eustachian tube function. AB - Sixty-three patients undergoing surgery to the nasal septum followed by bilateral packing had pre- and post-operative tympanometry in order to determine the effect on eustachian tube function. Fifty-five of the 126 ears tested (46 per cent) developed a reduction in middle ear pressure of at least 50 daPa; 76 per cent became normal within 24 hours of removing the nasal packs. All ears were asymptomatic and no patient had evidence of middle ear effusion. Nasal packing following septal surgery is a frequent cause of short-lasting eustachian tube dysfunction but rarely severe enough to cause symptoms or middle ear effusion. Tubal dysfunction is most likely due to a combination of surgical oedema and a direct effect of the nasal packing. PMID- 1875136 TI - Interpretation of maxillary sinus radiographs in children. AB - Nasal symptoms are a frequent cause of referral to paediatric ENT clinics. It is the policy of our unit to view sinus radiographs without a report at the initial clinic attendance. This study demonstrates there is no statistically significant difference in the interpretation of the radiographs between two ENT surgeons and a radiologist although there was a tendency for the radiologist to have a greater specificity. This finding may have financial implications. In addition a clear sinus radiograph is shown to be a significant negative finding. PMID- 1875137 TI - Submucous resection of the nasal septum as an outpatient procedure. AB - We report our experience of submucous resection of the nasal septum under local anaesthesia as an outpatient procedure. We have audited 50 consecutive cases and compared the results with a similar group of patients in whom the operation was carried out in the usual way under general anaesthesia. We have found the procedure to be safe, effective and economically advantageous. PMID- 1875138 TI - The microbiology of peritonsillar sepsis. AB - Pus obtained by needle aspiration of 91 peritonsillar abscesses was examined microbiologically. A positive culture was obtained in 55 patients (60 per cent). Sixty-four bacteriological isolates were grown. Forty patients had a pure growth of a single organism, of which 21 (53 per cent) were beta Haemolytic streptococci. Pure growths of Staphylococcus aureus were found in only three patients. Fifteen patients had mixed organisms, including anaerobes, in their pus and the resistance to penicillin was low. Only the bacteroides species were generally penicillin resistant. The vast majority of patients made a good recovery following needle drainage of the abscess and treatment with parenteral penicillin. The patients with a mixture of penicillin sensitive and penicillin resistant organisms also made a good clinical recovery following needle drainage and administration of parenteral penicillin. The relevance of these findings in the pathogenesis and management of peritonsillar sepsis is discussed. PMID- 1875139 TI - Histological changes in free jejunal grafts used in pharyngeal reconstruction. AB - A histological study was performed of biopsies taken from jejunal free grafts used in pharyngeal reconstruction. The main findings were a decreased crypt/villi ratio and a mild chronic inflammatory infiltrate. There was no evidence of metaplastic or dysplastic transformation. PMID- 1875140 TI - Subtotal parathyroidectomy for secondary hyperparathyroidism in chronic renal failure. AB - Twenty-seven patients on chronic haemodialysis and with secondary hyperparathyroidism underwent subtotal parathyroidectomy during the period 1985 1989. The operation was indicated by severe clinical symptoms and evidence of radiological abnormalities not responsive to conservative treatment (low phosphorus diet, phosphate binding substances, oral calcium and vitamin D). If despite intensive medical management, inadequate control of parathyroid hyperplasia continues surgical intervention becomes necessary. Ultra-sonography was performed pre-operatively in all 27 cases and detected 42 of 99 glands (42.5 per cent). Also scintigraphy was carried out in every patient but it gave a relatively low detection rate (24.5 per cent). Surgery was followed by improvement in 20 patients and progression of hyperparathyroidism in seven cases. Three of the seven patients failed to improve after subtotal parathyroidectomy, necessitating a re-intervention; the remaining four responded sufficiently to medical therapy. From our experience we conclude that subtotal parathyroidectomy for renal hyperparathyroidism is recommended. PMID- 1875141 TI - Malakoplakia of the temporal bone in a nine-month-old infant. AB - A case of malakoplakia, of the temporal bone in a nine-month-old male child is reported. The lesion presented as an aural polyp, associated with a lower motor neuron facial palsy. On exploration, the granuloma was noted to involve the temporal bone, eroding the bony labyrinth. It was successfully treated with surgical debridement, and antibiotics. A review of the relevant literature is presented. PMID- 1875142 TI - Meningitis from canine Pasteurella multocida following mastoidectomy. AB - A case of Pasteurella multocida meningitis, following a mastoidectomy is presented. The association of close contact with pets, many of which harbour Pasteurella multocida as part of their normal buccal flora. This case confirms the potential benefit of taking an ear swab prior to mastoid surgery and in seeking an appropriate 'pet' history. PMID- 1875143 TI - Total avulsion of an osseointegrated screw. AB - The close union achieved between pure grade titanium and healthy bone makes dislocation a rare event. We report the case of the total avulsion of an apparently well-integrated implant from a healthy mastoid bone. PMID- 1875144 TI - Rhinocerebral mucormycosis: use of liposomal amphotericin B. AB - Rhinocerebral mucormycosis is a rare but often fatal condition characterized by an aggressive necrotizing infection spreading from the nose to the paranasal sinuses, orbit and hence to the central nervous system. A case is reported in which a diabetic male with advanced mucormycosis was successfully treated by a combination of surgery, supportive therapy and liposomal amphotericin B. Liposomal delivery allows the drug to be both less toxic and more effective, and this is the first reported case of its use in rhinocerebral mucormycosis. PMID- 1875145 TI - Intracranial extension of a naso-ethmoid schwannoma. AB - A rare case of intracranial extension of a naso-ethmoid schwannoma is presented. Its subsequent removal with few sequelae confirmed the benign nature and good prognosis of the disease. PMID- 1875146 TI - Parapharyngeal space melioidosis in a diabetic. AB - Pseudomonas pseudomallei, a gram negative organism causing melioidosis, is found in tropical and subtropical regions. It may manifest as a pulmonary lesion, osteomyelitis, soft tissue abscesses, abscesses in various organs or in septicaemic form. Melioidosis of the parapharyngeal space has not been reported so far. A case of melioidosis of the parapharyngeal space which was successfully treated by drainage and prolonged antibiotic therapy is reported here. Melioidosis should be suspected in severe forms of deep neck space infection, especially if the patient comes from an endemic area. PMID- 1875147 TI - Small lymphocytic lymphoma presenting with simultaneous involvement of parotid and submandibular glands bilaterally, maxillary sinus, hard palate and optic nerve. PMID- 1875148 TI - Pseudoaneurysm of the internal carotid artery: a forgotten complication of tonsillitis? AB - Pseudoaneurysm of the internal carotid artery is an uncommon but potentially lethal complication of tonsillar or peritonsillar sepsis, which appears to have occurred more frequently prior to the introduction of penicillin. Management of such a case is discussed, and a literature review presented. PMID- 1875149 TI - Unusually placed oesophageal foreign body. AB - Oesophageal foreign bodies are common occurrences. A variety of cases have been reported in the past. We present here a unique case of an unusually placed foreign body. PMID- 1875150 TI - Nasal haemangiopericytoma. AB - Haemangiopericytoma is an uncommon vascular tumour frequently diagnosed with difficulty. The immunohistochemical findings of strong positivity to vimentin together with other diagnostic features (histological and ultrastructural) improves the certainty of its diagnosis. We report a case arising in the nose and outline diagnostic problems especially relating to histopathology. PMID- 1875151 TI - Use of the flexible oesophagoscope for the removal of an intramural oesophageal foreign body. PMID- 1875152 TI - Wegener's granulomatosis: familial occurrence. PMID- 1875153 TI - ADHD and LD connection. PMID- 1875154 TI - School-based assessment of attention deficit-hyperactivity disorder. AB - Schools are uniquely situated to provide information relevant to the assessment and treatment of Attention Deficit-Hyperactivity Disorder (ADHD) across a variety of tasks, settings, and observers. The importance of the school setting to the assessment and treatment of ADHD has resulted in the development of numerous measures appropriate for such assessment, but few guidelines for their use. The purpose of this article is to describe school-based assessment procedures and their relationship to ADHD. These procedures include teacher rating measures, direct observations in classrooms and on playgrounds, peer rating and sociometric measures, and permanent product measures such as academic performance. It is recommended that school-based assessment of ADHD involve the concurrent use of multiple measures to assess adequately the wide variety of symptoms associated with this disorder. It is further recommended that assessment serve the purpose of determining treatment efficacy to avoid unwarranted preoccupation with diagnostic issues that are as yet unresolved. The components of a comprehensive school-based assessment of ADHD are described, and their relationship to school based treatment is discussed. PMID- 1875155 TI - Cognitive training in ADHD children: less to it than meets the eye. AB - This article reviews cognitive training studies that have been carried out with children with attention deficit-hyperactivity disorder (ADHD) during the past decade. The efficacy of cognitive training as a single intervention and as an adjunct to stimulant treatment is discussed. The impact of training on the cognitive, academic, and behavioral functioning of youngsters with ADHD is summarized. Although this treatment modality is inherently appealing, there is little empirical support for its clinical utility with children with hyperactivity. PMID- 1875156 TI - Stimulant medication and parent training therapies for attention deficit hyperactivity disorder. AB - The present article provides a brief overview of the clinical use of two of the most commonly used and effective therapies for Attention Deficit-Hyperactivity Disorder (ADHD) in children: stimulant medication treatment and training parents in child behavior management skills. The clinical issues involved in the use of each treatment, as well as their limitations, are reviewed, along with evidence for their efficacy. It is concluded that ADHD is a developmental disorder of attention, impulse control, and regulation of activity level that requires multiple treatment methods, which must be applied over long time intervals if they are to produce an impact on the outcome of children with ADHD. PMID- 1875157 TI - Effects of stimulant medication on learning in children with ADHD. AB - It is well established that stimulant medication improves classroom manageability and attention in terms of time on task, but does stimulant medication improve learning or long-term academic achievement in children with ADHD? There is no clear evidence that it does, but there are at least two reasons why beneficial effects may be obscured in research studies and clinical practice: (1) Higher than-optimal doses may be prescribed if behavioral response (rather than cognitive response) is used to titrate the dose, and (2) treatment may be overinclusive if diagnostic groups are targeted in which a significant proportion of cases do not have favorable cognitive responses to medication. This article addresses these two issues and describes a large clinical series of patients who were evaluated using a double-blind medication assessment protocol designed to overcome some of the theoretical deficiencies suggested by these issues. PMID- 1875158 TI - Social impact of stimulant treatment for hyperactive children. AB - Most children diagnosed with ADHD have extensive and enduring problems in the social arena. Despite its limitations, the standard stimulant treatment regimen for children with ADHD is a useful therapeutic modality as well as an heuristic tool for increasing our understanding of both optimal and problematic interpersonal functioning. This article explores the social impact of stimulant treatment, delineating documented improvements, identifying elusive domains and puzzling patterns, and highlighting unintended and potentially undesirable outcomes. Medication-related changes in the behaviors and perceptions of the diagnosed child's adult caretakers are distinguished from those observed in peers, and the need to enhance our understanding of peer cultures is underscored. We present new findings on the effects of stimulant treatment on social cognition and affect, and then discuss the critical need to map the attributional sequelae of any treatment approach. The final sections explore contemporary controversies and improved strategies for balancing the costs, risks, and benefits of stimulant treatment in the service of enhancing interpersonal competence, satisfaction, and harmony. PMID- 1875159 TI - Procedural knowledge in mathematics: the role of the curriculum. AB - Over the last few years, the information processing model of cognition has become increasingly prominent in the field. With this model, and other related research in cognitive science, there is a greater appreciation for the role of instruction in learning theory. One of the model's central tenets is that, as learners become more competent, they move from declarative to procedural states of knowledge. Researchers have concerned themselves with the efficiency of this transition, as well as with any systematic misconceptions that develop along the way. A carefully developed curriculum addresses both of these concerns. This article will focus on three principles of curriculum development: the nature of examples, explicitness, and parsimony. Recently conducted research that supports these principles will also be discussed. It is suggested that special educators strongly consider these principles when selecting or developing curricular material for students with learning disabilities. PMID- 1875160 TI - Response patterns of children with learning disabilities: is impulsivity a stable response style? AB - A correlational analysis was conducted to assess the relationship among various assessment instruments, including Kagan, Rosman, Day, Albert, and Phillips's (1964) Matching Familiar Figures Test (MFFT), and actual classroom performance vis-a-vis impulsive responding. Subjects were 22 children (16 male, 6 female), ages 5 to 11 years, enrolled in an academic remediation program. The results do not support a relationship between impulsivity, as measured by the MFFT, and academic progress in a classroom setting. Implications for task-specific measures of impulsivity and remediation are discussed. PMID- 1875161 TI - On the dynamics of bursting systems. AB - The dynamics of three-variable models of bursting are studied. It is shown that under certain conditions, the dynamics on the attractor can be essentially reduced to two dimensions. The salient dynamics on the attractor can thus be completely described by the return map of a section which is a logistic interval map. Two specific bursting models from the literature are shown to fit in the general framework which is developed. Bifurcation of the full system for one case in investigated and the dynamical behavior on the attractor is shown to depend on the position of a certain nullcline. PMID- 1875162 TI - Minimization of intermediate concentrations as a suggested optimality principle for biochemical networks. II. Time hierarchy, enzymatic rate laws, and erythrocyte metabolism. AB - The multiobjective problem of minimizing all intermediate concentrations is solved for a model of glycolysis, the pentose monophosphate shunt and the glutathione system in human erythrocytes. It turns out that one solution out of four obtained corresponds qualitatively to the real system. Furthermore, it is shown that for any reaction system, the mentioned optimality principle implies distinct time hierarchy in that some reactions are infinitely fast and subsist in quasi-equilibrium. Finally, the relationships to the standard method of deriving enzymatic rate laws are discussed. PMID- 1875163 TI - Numerical simulation of thermal bone necrosis during cementation of femoral prostheses. AB - The implant of a femoral prosthesis is a critical process because of the relatively high temperature values reached at the bone/cement interface during the cementation of the infibulum. In fact, the cement is actually a polymer that polymerizes in situ generating heat. Moreover, the conversion of monomer into polymer is never 100%; this is dangerous because of the toxicity of the monomer. In this paper, we present a 3-D axisymmetric mathematical model capable of taking into account both the geometry of the implant and the chemical/physical properties of the cement. This model, together with its numerical simulation, thus represents a useful tool to set up the optimal conditions for the new materials developed in this orthopaedic field. The real complex geometry is assumed to be a bone/cement/metallic system having cylindrical symmetry, thus allowing the model to be reduced to two space variables. The cementation process is described by the Fourier heat equation coupled with a suitable polymerization kinetics. The numerical approximation is accomplished by semi-implicit finite differences in time and finite elements in space with numerical quadrature. The full discrete scheme amounts to solve linear positive definite symmetric systems preceded by an elementwise algebraic computation. We present various numerical simulations which confirm some critical aspects of this orthopaedic fixing technique such as thermal bone necrosis and the presence of unreacted residual monomer. PMID- 1875164 TI - Lupus antiribosomal P antisera contain antibodies to a small fragment of 28S rRNA located in the proposed ribosomal GTPase center. AB - The ribosomal P proteins are necessary for GTPase activity during protein synthesis. In addition to antibodies to the P proteins, sera from lupus patients contain anti-rRNA activity. To determine whether lupus antiribosomal sera recognize the region of 28S rRNA recently proposed to form part of the ribosomal GTPase center, an rRNA fragment corresponding to nucleotides (nt) 1922-2020 was transcribed in vitro and tested for antigenicity. 18 of 24 (75%) lupus sera containing anti-P antibodies, but only 2 of 24 (8%) lupus sera without anti-P, immunoprecipitated this rRNA fragment (p less than 0.001). The binding was specific, since no significant differences were observed between anti-P positive and negative lupus sera in binding to the RNA fragment transcribed in the antisense orientation or to a control region of rRNA. The majority of sera tested protected a rRNA fragment of approximately 68 nucleotides. To evaluate the fine specificity of the anti-28S antibodies, deletions and site-directed mutations were made in the RNA fragment. The anti-28S antisera required nt 1944-1955 for recognition and were remarkably sensitive to destabilizing as well as nondestabilizing mutations in the stems of the RNA fragments. Detection of antiprotein and anti-RNA antibodies directed against a functionally related domain in the ribosome, together with the remarkable specificity of anti-28S antibodies, strongly suggests a direct role for this region of the ribosome in initiating and/or maintaining antiribosomal autoantibody production. PMID- 1875165 TI - Endotoxin-neutralizing properties of the 25 kD N-terminal fragment and a newly isolated 30 kD C-terminal fragment of the 55-60 kD bactericidal/permeability increasing protein of human neutrophils. AB - The bactericidal/permeability-increasing protein (BPI) of polymorphonuclear leukocytes (PMN) is a potent cytotoxin, specific for Gram-negative bacteria, that also inhibits endotoxin activity by neutralizing isolated bacterial lipopolysaccharides (LPS). We have previously shown that an isolated 25 kD N terminal fragment of human BPI carries all the antibacterial activities of the parent 55-60 kD molecule. In this study we have compared the LPS-neutralizing activities of human holo-BPI, the N-terminal fragment and a 30 kD C-terminal fragment that we have now isolated. We show that the N-terminal fragment also has LPS-neutralizing activity as detected by inhibition (up to 95%) of (a) activation by LPS of procoagulant proteases in Limulus amebocyte lysates, (b) LPS "priming" of PMN, and (c) LPS-mediated production of tumor necrosis factor in whole human blood. Holo-BPI and the 25 kD fragment have similar neutralizing potency (in nanomolar range) in all assays toward "smooth" LPS from Escherichia coli O111:B4 and O55:B5 (possessing long chain polysaccharide or O-antigen), and "deep rough" LPS from Salmonella minnesota Re595 mutant (possessing no O-antigen). The C terminal fragment of BPI is devoid of antibacterial activity when tested against BPI-sensitive E. coli J5, but does have endotoxin-neutralizing activity. This activity is weak relative to holo-BPI and the 25 kD N-terminal fragment in the Limulus and PMN-priming assay, but is comparable for inhibition of TNF production in whole blood. We conclude that the principal determinants for LPS recognition and neutralization, like those for antibacterial action, reside in the N-terminal half of the BPI molecule, but that sites within the C-terminal half can also contribute to BPI-LPS interaction once LPS is detached from the bacterial envelope. PMID- 1875166 TI - Ultrastructural localization of albumin transport across the cerebral microvasculature during experimental meningitis in the rat. AB - Injury to the blood brain barrier (BBB) is a fundamental sequela of bacterial meningitis, yet the precise mechanism facilitating exudation of albumin across the endothelium of the cerebral microvasculature remains conjectural. After intracisternal inoculation of Escherichia coli (0111:B4) lipopolysaccharide in rats to elicit a reversible meningitis and BBB injury, we utilized in situ tracer perfusion and immunolabeling procedures to identify by transmission electron microscopy the precise topography and microvascular exit pathway(s) of bovine serum albumin (BSA). Results revealed that during meningitis there was: (a) an inducible increase in immunodetectable monomeric BSA binding to the luminal membrane of all microvascular segments in the pia-arachnoid and superficial brain cortex; (b) similar uptake of both colloidal Au-BSA (as well as monomeric BSA) by plasmalemmal vesicles but no detectable transcytosis to the abluminal side; and (c) predominant exit of both perfused Au-BSA and immunodetectable monomeric BSA through open intercellular junctions of venules in the pia-arachnoid. This was corroborated in separate experiments documenting focal pial venular leaks of in situ perfused 0.01% colloidal carbon black during experimental meningitis. These results provide precise localization of BBB injury in meningitis to meningeal venules, confirm a paracellular exit pathway of albumin via open intercellular junctions, and suggest an injury mechanism amenable to specific therapeutic intervention. PMID- 1875167 TI - Evidence that natural murine soluble interleukin 4 receptors may act as transport proteins. AB - The present studies were undertaken to determine whether the interleukin 4 binding proteins (IL-4BPs) previously identified in the biological fluids of mice are soluble forms of IL-4Rs. We also studied the binding properties of IL-4BPs in order to gain insight into their physiological role in vivo. Affinity-purified IL 4BPs and recombinant soluble IL-4Rs generated similar one-dimensional (Cleveland) peptide maps after digestion with either Staphylococcus aureus V8 protease or trypsin, indicating structural similarities. Furthermore, a rat mAb directed against the murine IL-4Rs immunoprecipitated the IL-4BPs and completely inhibited binding of 125I-IL-4 to a purified preparation of IL-4BPs. Taken together these data indicate that the IL-4BPs are soluble IL-4Rs. At 4 degrees C the IL-4BPs competitively inhibited the binding of IL-4 to membrane IL-4Rs but their ability to prevent binding of IL-4 to cells at 37 degrees C, at the same concentrations, was significantly reduced. Kinetic binding studies of soluble IL-4BPs vs. membrane IL-4Rs disclosed important differences in their rates of dissociation from IL-4. Whereas dissociation at 4 degrees C was slow for both, dissociation of IL-4 from IL-BPs at 37 degrees C was considerably faster (t 1/2 of 2 min) than dissociation of IL-4 from membrane IL-4Rs (t 1/2 of approximately 69 min). Temperature-dependent changes in dissociation kinetics were reversible, and could not be accounted for by either inactivation of the IL-4BPs at 37 degrees C or receptor internalization. Additional experiments also demonstrated that when IL 4BPs bind to IL-4 at 37 degrees C, the IL-4/IL-4BPs complex can rapidly dissociate, allowing IL-4 to bind to membrane IL-4Rs. In addition, binding of IL 4 by the IL-4BPs protects IL-4 from proteolytic degradation. Taken together, these results suggest that the IL-4BPs are naturally occurring forms of soluble IL-4Rs and that some of their properties (fast dissociation kinetics and protection of IL-4 from proteolysis) are consistent with a potential role as carrier proteins for IL-4 in the circulation. PMID- 1875168 TI - Differentiation of primitive human multipotent hematopoietic progenitors into single lineage clonogenic progenitors is accompanied by alterations in their interaction with fibronectin. AB - We have previously demonstrated that primitive progenitors from human bone marrow termed long term bone marrow culture initiating cells (LTBMC-IC) adhere avidly to irradiated bone marrow stroma, while more mature clonogenic progenitors fail to do so. In this study we examine the interaction between these progenitors and components of the bone marrow stroma. (a) We demonstrate that both primitive LTBMC-IC and more mature clonogenic progenitors adhere to intact fibronectin. (b) Primitive LTBMC-IC and multi-lineage CFU-MIX progenitors adhere to the 33/66 kD COOH-terminal heparin-binding cell-adhesion promoting fragment of fibronectin, but adhere significantly less to its 75 kD RGDS-dependent cell-binding fragment. In contrast, more differentiated single-lineage progenitors adhere equally well to the 33/66 kD RGDS independent and the 75 kD RGDS-dependent cell-adhesion fragments of fibronectin. (c) Both primitive LTBMC-IC and clonogenic progenitors adhere to the three known cell-attachment sites in the 33/66 kD cell-adhesion promoting fragment, FN-C/H I, FN-C/H II and CS1. However, LTBMC-IC and CFU-MIX progenitors adhere significantly better to FN-C/H II than to the flanking FN-C/H I and CS1 cell-attachment sites. In contrast, single-lineage progenitors adhere equally well to all three cell attachment sites in the 33/66 kD cell-adhesion promoting fragment. (d) Finally, adhesion of primitive LTBMC-IC to intact irradiated stroma can be inhibited partially by peptide FN-C/H II and almost completely by a combination of FN-C/H II and peptide FN-C/H I and CS1. This study demonstrates that adhesive interactions between primitive hematopoietic progenitors and the extracellular matrix component fibronectin can occur. Specific changes in adhesion to the 33/66 kD cell-adhesion promoting fragment and the 75 kD RGDS-dependent cell-adhesion fragment of fibronectin are associated with differentiation of primitive multi-lineage progenitors into committed single lineage progenitors. Such differences in adhesive interaction with fibronectin may allow hematopoietic progenitors at various stages of differentiation to interact with specific supportive loci of the bone marrow microenvironment. Finally, the ability to block adhesion of LTBMC-IC to intact irradiated stroma with peptides FN-C/H II, FN-C/H I and CS1 suggests that receptors responsible for this interaction may be important in the homing of primitive progenitors to the bone marrow. PMID- 1875169 TI - Mature murine B and T cells transferred to SCID mice can survive indefinitely and many maintain a virgin phenotype. AB - To seek information on the potential lifespan of normal B and T lymphocytes, lymph node (LN) cells from unprimed mice were transferred to H-2-identical severe combined immunodeficiency (SCID) hosts. At a population level, the donor B and T cells survived for at least 10 mo post-transfer with no reduction in their numbers. In terms of antibody production, LN-injected SCID mice remained responsive to several different antigens and contained unprimed precursors of memory cells for greater than or equal to 6 mo post-transfer. Most of the B and T cells recovered from LN-injected SCID mice expressed the typical virgin phenotype of mature lymphocytes from young mice. These findings suggest that many of the transferred lymphocytes might have remained in interphase as virgin cells from the time of injection. This did not apply to all of the transferred cells, however, because 20-40% of CD4+ cells from long-term SCID hosts displayed a memory phenotype, 7% incorporated 2-bromodeoxyuridine over 5 d, and total numbers of B and T cells increased gradually (twofold) over a 10-mo period. Collectively, the data favor the view that the pool of mature B and T cells in adult mice is largely self sufficient: some of the cells proliferate, presumably in response to environmental antigens, but many mature cells can remain quiescent for prolonged periods. Input of new cells from the primary lymphoid organs continues, but at a much reduced rate relative to young life. PMID- 1875170 TI - Presentation of viral antigen to class I major histocompatibility complex restricted cytotoxic T lymphocyte. Recognition of an immunodominant influenza hemagglutinin site by cytotoxic T lymphocyte is independent of the position of the site in the hemagglutinin translation product. AB - Class I major histocompatibility complex (MHC) restricted T lymphocytes preferentially recognize fragments of polypeptides processed through a nonendosomal presentation pathway. At present the intracellular compartment(s) in which polypeptide fragmentation occurs and factors which influence the formation of an antigenic epitope are not well understood. To assess the role of residues flanking an antigenic site in the generation of the antigenic moiety recognized by class I MHC restricted T lymphocytes we have moved the coding sequence for an immunodominant H-2Kd restricted site on the influenza A/JAPAN/57 hemagglutinin (residues 202-221) by site-directed mutagenesis to six different positions along the coding sequence of the hemagglutinin gene. We have found that all six classes of mutants are recognized by MHC class I restricted T cells as efficiently as the wild type hemagglutinin gene product. Thus neither N-terminal to C-terminal position within the translation product nor sequences flanking the antigenic site influence processing. PMID- 1875171 TI - Granulocyte/macrophage colony-stimulating factor and interleukin 3 release from human peripheral blood eosinophils and neutrophils. AB - Human peripheral blood eosinophils released eosinophil survival-enhancing activity when stimulated with the calcium ionophore, ionomycin. The release of activity was detected as early as 3 h after stimulation and was inhibited by an immunomodulating agent, cyclosporin A. The survival-enhancing activity was completely abolished by treatment with anti-interleukin 3 (IL-3) and anti granulocyte/macrophage colony-stimulating factor (GM-CSF) monoclonal antibodies. Moreover, IL-3 and GM-CSF were measurable in ionomycin-stimulated eosinophil supernatants by immunoassay. Eosinophils produced approximately one-half as much IL-3 and one-fifth as much GM-CSF as ionomycin-stimulated mononuclear cells. Neutrophils also produced IL-3 and GM-CSF, but the amounts were less than those produced by eosinophils. These observations suggest a novel role for eosinophils in pathophysiology of allergic inflammation and host defense mechanisms. PMID- 1875173 TI - The growing ferment. Access to care. PMID- 1875172 TI - Expression of mRNA and immunoreactivity for the granulocyte/macrophage colony stimulating factor in activated human eosinophils. AB - Using in situ hybridization, we have shown that activated human peripheral blood eosinophils express mRNA for granulocyte/macrophage colony-stimulating factor (GM CSF). Between 15 and 27% of eosinophils gave positive hybridization signals for GM-CSF mRNA after stimulation with the calcium ionophore A23187 or interferon gamma, and 4 and 6% after incubation with interleukin 3 (IL-3) or IL-5. Activated eosinophils also gave specific immunoreactivity with an anti-GM-CSF polyclonal antibody, suggesting translation of the mRNA. These data indicate that eosinophils may be an important source of GM-CSF at sites of allergic inflammation. Furthermore, the identification of GM-CSF production by human eosinophils suggests that the pro-inflammatory potential of this cell type may be substantially greater than hitherto recognized. PMID- 1875174 TI - Prescription for saving our profession. PMID- 1875175 TI - Bioethics training. PMID- 1875176 TI - New St. George needed. PMID- 1875177 TI - Medical paperwork. PMID- 1875178 TI - Regarding the safety of silicone implants. PMID- 1875179 TI - Bone marrow culture for diagnosis of mycobacterial and fungal infections in febrile patients. AB - The perception and evaluation of patients with fever are constantly evolving. Due to sophisticated technology and financial constraints, increasing numbers of tests are performed earlier in patient evaluation. One is bone marrow culture for mycobacteria and fungi. To assess the yield of this procedure, we reviewed the results of cultures performed from 1982-1986 at Shands Hospital at the University of Florida. There were 124 patients so evaluated. No fungal cultures were positive. Four mycobacterial cultures were positive: three Mycobacterium avium intracellulare, all in patients with AIDS (Acquired Immune Deficiency Syndrome), and one Mycobacterium tuberculosis in a patient with disseminated disease. Three patients ultimately found by other means to have disseminated mycobacterial infection were culture negative. We conclude that this procedure is of very low yield and only warranted in the patient with severe immunocompromise or the patient with strong clinical evidence of disseminated tuberculosis. PMID- 1875180 TI - Left ventricular aneurysm and intraventricular thrombi. Investigation and surgical correlations. AB - Formation of a left ventricular aneurysm and intraventricular thrombus represents one of the dreaded sequelae of coronary artery disease and acute myocardial infarction. The present emphasis is to reduce the incidence by reduction of cholesterol and fats, elimination of smoking, improved detection and control of hypertension and diabetes mellitus. Earlier diagnosis is available with stress testing and other noninvasive techniques. Cardiac catheterization allows detection of occlusive lesions. The CASS and other studies increasingly prove that percutaneous angioplasty and coronary artery bypass surgery improve life expectancy and implicitly should reduce the incidence of acute myocardial infarction. In the setting of the latter, thrombolytic agents may reduce the amount of myocardial injury. Despite these measures, formation of left ventricular aneurysms remains a common occurrence. Diagnosis and management are critical issues to the cardiac surgeon. PMID- 1875181 TI - Elements of physician advocacy. PMID- 1875182 TI - Preventive health care for older persons. PMID- 1875184 TI - It takes a worried doctor to sing a worry song. PMID- 1875183 TI - Thyroid hormone. Basis for its hypocholesterolemic effect. AB - The liver is the key organ involved in cholesterol homeostasis. Thyroid hormone binds to nuclear receptors in the liver and thereby acts to alter the expression of several genes coding for proteins involved in cholesterol homeostasis. The expression of apo B-100, the major protein of LDL, is markedly decreased by thyroid hormone while expression of apo A-I, the major protein of HDL, is profoundly increased by thyroid hormone. The thyroid hormone acts to increase hepatic LDL receptor and cholesterol 7 alpha hydroxylase gene expression. The increase in cholesterol 7 alpha hydroxylase, the enzyme which catalyzes the rate limiting reaction in the degradation of cholesterol to form bile acids, occurs the most rapidly (within one hour) and requires low physiological doses of hormone. Inspection of the 5' flanking region of the cholesterol 7 alpha hydroxylase gene revealed two possible thyroid responsive elements, suggesting that thyroid hormone may exert a primary effect on this gene. The alterations in gene expression produced by thyroid hormone would be expected to result in decreased LDL levels because of decreased apo B-100 synthesis, increased HDL to assist in reverse cholesterol transport from peripheral tissue to the liver, increased removal of LDL from blood by increased hepatic LDL receptors, and increased elimination of cholesterol as neutral sterols and bile acids due to increased cholesterol 7 alpha hydroxylase. These actions would lead to lower serum cholesterol levels. PMID- 1875185 TI - Fusion of influenza virions with a planar lipid membrane detected by video fluorescence microscopy. AB - The fusion of individual influenza virions with a planar phospholipid membrane was detected by fluorescence video microscopy. Virion envelopes were loaded with the lipophilic fluorescent marker octadecylrhodamine B (R18) to a density at which the fluorescence of the probe was self-quenched. Labeled virions were ejected toward the planar membrane from a micropipette in a custom-built video fluorescence microscope. Once a virion fused with the planar membrane, the marker was free to diffuse, and its fluorescence became dequenched, producing a flash of light. This flash was detected as a transient spot of light which increased and then diminished in brightness. The diffusion constants calculated from the brightness profiles for the flashes are consistent with fusion of virus to the membrane with consequent free diffusion of probe within the planar membrane. Under conditions known to be fusigenic for influenza virus (low pH and 37 degrees C), flashes appeared at a high rate and the planar membrane quickly became fluorescent. To further establish that these flashes were due to fusion, we showed that red blood cells, which normally do not attach to planar membranes, were able to bind to membranes that had been exposed to virus under fusigenic conditions. The amount of binding correlated with the amount of flashing. This indicates that flashes signaled the reconstitution of the hemagglutinin glycoprotein (HA) of influenza virus, a well-known erythrocyte receptor, into the planar membrane, as would be expected in a fusion process. The flash rate on ganglioside-containing asolectin membranes increased as the pH was lowered. This is also consistent with the known fusion behavior of influenza virus with cell membranes and with phospholipid vesicles. We conclude that the flashes result from the fusion of individual virions to the planar membrane. PMID- 1875186 TI - The role of N-acetylneuraminic (sialic) acid in the pH dependence of influenza virion fusion with planar phospholipid membranes. AB - It is known that fusion of influenza virus to host cell membranes is strongly promoted by acidic pH. We have determined conditions required to obtain pH dependent fusion of influenza virus to planar bilayer membranes. The rate of viral fusion was determined from the flash rate of R18-labeled virions delivered to the surface of the planar membrane by pressure-ejection from a pipette. For a bilayer formed only of phospholipids and cholesterol, the fusion rate was independent of pH and unaffected by the phospholipid composition. When the gangliosides GD1a + GT1b were included in the planar membrane, however, the fusion rate varied steeply with pH. The rate at pH 7.4 in the presence of the gangliosides was about an order of magnitude less than in their absence. At pH less than approximately 5.5, the rate was about an order of magnitude greater in the presence of gangliosides than in their absence. The fusion rate with planar membranes containing globoside, a ceramide-backboned glycolipid, was also independent of pH, indicating that the pH dependence required sialic acid on the carbohydrate moiety of the glycolipid. The gangliosides GM1a and GM3, both of which possess sialic acid, produced the same pH-dependent fusion rate as seen with GD1a + GT1b, indicating that the presence, but not the location, of terminal sialic acids is critical. Incubating virus with soluble sialyllactose blocked fusion to both ganglioside-free and ganglioside-containing planar membranes. These results show that the pH dependence of influenza virion fusion arises from the interaction of the sialic acid receptor with the influenza hemagglutinin. A model for sialic acid-hemagglutinin interactions accounting for pH-dependent fusion is presented. PMID- 1875187 TI - Multiple conductance states of the light-activated channel of Limulus ventral photoreceptors. Alteration of conductance state during light. AB - The properties of light-dependent channels in Limulus ventral photoreceptors have been studied in cell-attached patches. Two sizes of single-channel events are seen during illumination. Previous work has characterized the large (40 pS) events; the goal of the current work was to characterize the small (15 pS) events and determine their relationship to the large events. The small events are activated by light rather than as a secondary result of the change in membrane voltage during light. The mean open time of the small events is 1.34 +/- 0.49 ms (mean +/- SD, n = 15), approximately 50% of that of the large events. The large and small events have the same reversal potential and a similar dependence of open-state probability on voltage. Evidence that these events are due to different conductance states of the same channel comes from analysis of relatively infrequent events showing a direct transition between the 15 and 40-pS levels. Furthermore, large and small events do not superpose, even at positive voltages when the probability of being open is very high, as would be predicted if the two-sized events were due to independent channels. Expression of the different conductance states is not random; during steady illumination there are alternating periods of several hundred milliseconds in which there are consecutive, sequential large events followed by periods in which there are consecutive, sequential small events. At early times during the response to a step of light, the large conductance state is preferentially expressed. At later times, there is an increase in the relative contribution of the low conductance state. These findings indicate that there is a process that changes the preferred conductance state of the channel. This alteration has functional importance in the process of light adaptation. PMID- 1875188 TI - Selectivity and gating of the type L potassium channel in mouse lymphocytes. AB - Type l voltage-gated K+ channels in murine lymphocytes were studied under voltage clamp in cell-attached patches and in the whole-cell configuration. The kinetics of activation of whole-cell currents during depolarizing pulses could be fit by a single exponential after an initial delay. Deactivation upon repolarization of both macroscopic and microscopic currents was mono-exponential, except in Rb Ringer or Cs-Ringer solution in which tail currents often displayed "hooks," wherein the current first increased or remained constant before decaying. In some cells type l currents were contaminated by a small component due to type n K+ channels, which deactivate approximately 10 times slower than type l channels. Both macroscopic and single channel currents could be dissected either kinetically or pharmacologically into these two K+ channel types. The ionic selectivity and conductance of type l channels were studied by varying the internal and external permeant ion. With 160 mM K+ in the cell, the relative permeability calculated from the reversal potential with the Goldman-Hodgkin-Katz equation was K+ (identical to 1.0) greater than Rb+ (0.76) greater than NH4+ = Cs+ (0.12) much greater than Na+ (less than 0.004). Measured 30 mV negative to the reversal potential, the relative conductance sequence was quite different: NH4+ (1.5) greater than K+ (identical to 1.0) greater than Rb+ (0.5) greater than Cs+ (0.06) much greater than Na+, Li+, TMA+ (unmeasurable). Single channel current rectification resembled that of the whole-cell instantaneous I-V relation. Anomalous mole-fraction dependence of the relative permeability PNH4/PK was observed in NH4(+)-K+ mixtures, indicating that the type l K+ channel is a multi-ion pore. Compared with other K+ channels, lymphocyte type l K+ channels are most similar to "g12" channels in myelinated nerve. PMID- 1875189 TI - Permeant ion effects on the gating kinetics of the type L potassium channel in mouse lymphocytes. AB - Permeant ion species was found to profoundly affect the gating kinetics of type l K+ currents in mouse T lymphocytes studied with the whole-cell or on-cell patch gigaohm-seal techniques. Replacing external K+ with Rb+ (as the sole monovalent cation, at 160 mM) shifted the peak conductance voltage (g-V) relation by approximately 20 mV to more negative potentials, while NH4+ shifted the g-V curve by 15 mV to more positive potentials. Deactivation (the tail current time constant, tau tail) was slowed by an average of 14-fold at -70 mV in external Rb+, by approximately 8-fold in Cs+, and by a factor of two to three in NH4+. Changing the external K+ concentration, [K+]o, from 4.5 to 160 mM or [Rb+]o from 10 to 160 mM had no effect on tau tail. With all the internal K+ replaced by Rb+ or Cs+ and either isotonic Rb+ or K+ in the bath, tau tail was indistinguishable from that with K+ in the cell. With the exception of NH4+, activation time constants were insensitive to permeant ion species. These results indicate that external permeant ions have stronger effects than internal permeant ions, suggesting an external modulatory site that influences K+ channel gating. However, in bi-ionic experiments with reduced external permeant ion concentrations, tau tail was sensitive to the direction of current flow, indicating that the modulatory site is either within the permeation pathway or in the outer vestibule of the channel. The latter interpretation implies that outward current through an open type l K+ channel significantly alters local ion concentrations at the modulatory site in the outer vestibule, and consequently at the mouth of the channel. Experiments with mixtures of K+ and Rb+ in the external solution reveal that deactivation kinetics are minimally affected by addition of Rb+ until the Rb+ mole fraction approaches unity. This relationship between mole fraction and tau tail, together with the concentration independence of tau tail, was hard to reconcile with simple models in which occupancy of a site within the permeation pathway prevents channel closing, but is consistent with a model in which a permeant ion binding site in the outer vestibule modulates gating depending on the species of ion occupying the site. A description of the ionic selectivity of the type l K+ channel is presented in the companion paper (Shapiro and DeCoursey, 1991b). PMID- 1875190 TI - Indian bunchy top disease of tomato plants is caused by a distinct strain of citrus exocortis viroid. AB - A viroid has been isolated from tomato plants affected by Indian bunchy top disease of tomato (Lycopersicon esculentum Mill.). In dot blot hybridization assays with 32P-labelled cRNA probes specific for the detection of various viroids, the Indian viroid was shown to be most closely related to the citrus exocortis viroid (CEVd). Sequence determination showed that the viroid consists of 372 nucleotides and confirmed its close relationship with CEVd. The viroid, for which we propose the acronym CEVd-t, differs from the Australian CEVd strains A and B by 36 and 47 nucleotides, respectively, and from the Spanish grapevine isolate by 52 changes. A phylogenetic analysis confirmed the closet relationship with CEVd in all structural domains, except the pathogenicity and left-terminal domains, which are closely related to the corresponding domains of the potato spindle tuber and tomato apical stunt viroids, respectively. PMID- 1875191 TI - Artificial defective interfering RNAs derived from brome mosaic virus. AB - Naturally occurring defective interfering RNAs (DI-RNAs) greatly reduce the accumulation of their helper virus in vivo, but are rarely associated with plant positive-strand RNA viruses. Deletion mutants pRNA-2 M/S and pRNA-2 E/S, derived from brome mosaic virus (BMV) genomic RNA-2, replicated in a manner dependent on BMV RNA-1 and -2, and effectively interfered with their accumulation in barley protoplasts. Based on their mode of replication, these mutant RNAs have been termed parasitic RNAs (pRNAs). When present with RNA-1 and -2 at low inoculum amounts, pRNA-2 M/S and pRNA-2 E/S reduced the level of replication of RNA-2, the parental RNA, by 37% and 64%, respectively. Greater amounts of pRNA in the inoculum completely eliminated the replication of both RNA-1 and -2. Mutations that prevented translation of truncated proteins from the pRNAs did not affect interference, but those that reduced pRNA replication decreased their ability to interfere with genomic RNA replication. At a molar pRNA: genomic RNA inoculum ratio of 1.5:1, pRNA-2 E/S reduced the accumulation of all helper virus RNAs by greater than 60%. This occurred in the presence of wild-type RNA-3 or delta SGP RNA-3, a deletion mutant of RNA-3 that lacks the subgenomic promoter necessary for coat protein expression, demonstrating that the interference mediated by the pRNAs was not effected by encapsidation. These data indicate that the expression of pRNAs that function as artificial DI-RNAs in transgenic plants may be an approach for inducing resistance to virus infection which is applicable to a wide range of plant viruses. PMID- 1875192 TI - A spontaneous red clover necrotic mosaic virus mutant with a truncated movement protein. AB - A spontaneous red clover necrotic mosaic virus mutant, TpM-341, was isolated by multiple passage of Czechoslovakian isolate TpM-34 in beans, followed by three cycles of single lesion isolation in cowpea and in Chenopodium quinoa. The symptoms induced in cowpea by TpM-34 and TpM-341 differed. TpM-34 gave rise to chlorotic lesions which expanded with time, often becoming confluent with adjacent lesions, and developed necrotic margins; the plants became systemically infected. TpM-341 induced necrotic lesions which, once developed, did not expand further; plants did not become systemically infected. Analysis of pseudorecombinants formed between the RNAs of TpM-34 and TpM-341 showed that RNA 2 determined the difference in symptoms. Comparison of the nucleotide sequence of the open reading frames (ORFs) encoding the P2 movement proteins of the two isolates revealed only one difference, a deletion of an A residue in a sequence of four A residues (nucleotides 790 to 793). Construction of full-length TpM-34 and TpM-341 RNA 2 cDNA clones, from which infectious RNA 2 could be transcribed in vitro, and in vitro mutagenesis of a cDNA clone of TpM-341, confirmed that the difference in the symptoms induced by TpM-341 was caused by the loss of this A residue. This single base deletion was predicted to cause a translational frame shift in the P2 ORF causing the loss of 88 amino acids at the C terminus which were replaced by a sequence of 34 different amino acids, producing a truncated P2 protein. In vitro translation of RNA 2 transcribed from cDNA clones showed that RNA with four or three A residues starting at nucleotide 790 produced proteins of Mr 36K and 30K respectively, in agreement with the predictions based on the nucleotide sequence. PMID- 1875193 TI - Transgenic plants and insect cells expressing the coat protein of arabis mosaic virus produce empty virus-like particles. AB - The 3' end of the RNA-2 of arabis mosaic virus (ArMV) was cloned and sequenced. The N-terminal amino acid sequence of the virion coat protein was determined by Edman degradation and the corresponding coding region identified. This gene was modified at the 5' and 3' ends by use of mismatched primers in the polymerase chain reaction (PCR), in order to facilitate the cloning of the gene, and to provide it with a methionine initiation codon. The modified cloned gene was expressed in transgenic plants, recombinant baculovirus-infected insect cells and bacteria. Both the insect cells and the plants expressing the modified coat protein gene contained empty virus-like particles (VLPs) similar to the empty virus shells found in plants infected with ArMV. These VLPs were not detected in the Escherichia coli expressing the coat protein. Analysis of the primary amino acid sequence in the ArMV coat protein revealed extensive regions of identity with that of grapevine fanleaf virus. Patterns in these identities may reflect a three-domain organization of the proteins. PMID- 1875194 TI - The nucleotide sequence and luteovirus-like nature of RNA 1 of an aphid non transmissible strain of pea enation mosaic virus. AB - An examination of the genomic strategy of pea enation mosaic virus (PEMV) RNA 1 has verified strong organizational and sequence relationships between PEMV and the beet western yellows-potato leafroll luteovirus subgroup. Sequence analysis of RNA 1 demonstrated five predominant open reading frames (ORFs). The extreme 5' ORF encodes a 34K product of unknown function. The second ORF encodes an 84K product which overlaps 90% of ORF 1 (in a unique reading frame) and is expressed by internal initiation beginning at the second start codon from the 5' terminus. This protein contains a protease-like motif characteristic of serine- and cysteine-based proteases, suggesting involvement in post-translational processing of viral translation products. The third ORF is characterized by a number of RNA polymerase motifs and a helicase-like motif typical of RNA-dependent RNA polymerases. It overlaps (out of frame) the ORF 2 product and is proposed to be expressed by a frameshift fusion of the ORF 2 and ORF 3 products. The fourth ORF encodes the viral coat protein, and is immediately followed in frame by a 33K ORF thought to represent the aphid transmission subunit of the PEMV virion. Northern blot analysis of polysome-associated RNA suggests that both products are expressed from an 1800 nucleotide subgenomic mRNA, with the 33K product expressed as a read-through fusion with the coat protein monomer. PMID- 1875195 TI - Molecular evidence for a role of domestic ducks in the introduction of avian H3 influenza viruses to pigs in southern China, where the A/Hong Kong/68 (H3N2) strain emerged. AB - The haemagglutinins (HAs) of five H3 influenza A viruses isolated from domestic ducks and one from a goose in southern China were analysed antigenically and genetically. The patterns of reactivity of two of the duck viruses and the goose virus with a panel of monoclonal antibodies to 10 different epitopes on the H3 HA were similar to those of influenza viruses isolated from wild ducks and pigs, as well as those of the earliest human H3 viruses. The other three isolates from domestic ducks were different from each other and from these viruses antigenically. Sequence analysis revealed that the HA genes of the two duck viruses and the goose virus were closely related to those of isolates from wild ducks and pigs; the identities between the deduced amino acid sequence of the HA of one of the isolates from domestic ducks and those of isolates from a wild duck and a pig were 98.7% and 99.5%, respectively. The antigenic and genetic similarity between these H3 HAs suggests that in southern China, the hypothetical influenza epicentre, domestic ducks may have played a role in the introduction of avian influenza viruses to pigs from feral ducks. The findings also support the hypothesis that the pig was a 'mixing vessel', producing a new human pandemic strain, A/Hong Kong/68 (H3N2), by genetic reassortment. PMID- 1875196 TI - Replication of influenza A viruses in an avian macrophage cell line. AB - The virulent avian influenza virus A/Ty/Ont/7732/66 (H5N9) (Ty/Ont) causes severe destruction of the lymphoid cells in infected birds. Previous studies have suggested that viral infection of macrophages may be involved. However, Ty/Ont failed to replicate productively in primary cultures of chicken macrophages. Therefore, in an effort to develop an in vitro system for our studies, we examined the susceptibility of an avian macrophage cell line, HD11, to Ty/Ont. We found that Ty/Ont replicated in the HD11 cells to high titres, as measured by haemagglutination (HA) assays and infectivity yields. To determine whether this property was unique to Ty/Ont, we also examined the replication of influenza viruses representative of all 13 HA subtypes and an attenuated variant of Ty/Ont. All of the tested viruses replicated in HD11 cells; the avirulent strains required the presence of trypsin in the culture medium whereas virulent viruses and the attenuated variant of Ty/Ont did not. These results suggest that the HD11 cells can support the replication of a wide variety of influenza viruses and that this continuous avian cell line may prove useful for in vitro studies on these viruses. PMID- 1875197 TI - Analysis of the glycoprotein gene of Tacaribe virus and neutralization-resistant variants. AB - We have previously generated neutralization-resistant variants of Tacaribe virus in the presence of a monoclonal antibody (MAb) specific for the envelope glycoprotein. The envelope glycoprotein precursor (GPC) genes of two variant viruses were sequenced following polymerase chain reaction amplification of a specific region of the Tacaribe virus S RNA, and compared with the GPC gene of the parental virus. Multiple nucleotide changes in the 3' half of the GPC gene were identified in the variants, suggesting that this part of the gene codes for the envelope glycoprotein of Tacaribe virus recognized by the MAb. Both variants showed unique amino acid substitutions up to 166 residues apart, suggesting that the most likely basis for neutralization resistance was a change in an epitope in which the critical residues are juxtaposed by conformation rather than by proximity in coding. PMID- 1875198 TI - Expression strategy of the potato virus X triple gene block. AB - The mode of expression of the overlapping genes of the triple block positioned internally in potato virus X (PVX) RNA was examined. The results of In vitro translation of synthetic RNA transcripts and natural PVX-specific methylmercuric hydroxide-denatured dsRNAs suggest that the 25K protein is expressed as a single translation product of the 2.1 kb subgenomic (sg) RNA and that both the 12K and 8K proteins are expressed from the same 1.4 kb sgRNA. PMID- 1875199 TI - Peripheral wear of Wagner resurfacing hip arthroplasty acetabular components. AB - One hundred nine Wagner resurfacing arthroplasty acetabular components retrieved at revision surgery were examined for type, depth, and extent of wear at the periphery of the components. Ninety-two components were found to have evidence of peripheral wear caused by impingement of the femoral neck on the edge of the component. The thickness of the wall loss due to this impingement wear was found to be less the farther that measurements were taken from the edge of the component. Thus, when those components with any evidence of impingement wear were analyzed, it was found that significantly fewer components had evidence of impingement at depths of 3 mm and 5 mm in from the edge of the component. It is suggested that future designs of resurfacing hip arthroplasty acetabular components should be at least 3 mm and possibly 5 mm less than a hemisphere. This is likely to lead to less impingement on the femoral neck and therefore less cause for mechanical loosening and less production of wear debris. PMID- 1875200 TI - An evaluation of the efficacy of postoperative blood salvage after total joint arthroplasty. A prospective randomized trial. AB - The efficacy of a postoperative blood salvage system was assessed in 239 consecutive patients undergoing total knee or total hip arthroplasty. Patients were randomly allocated to either a control group using a standard drainage system or to the study group using the Solcotrans blood salvage canister. The median amount of homologous blood required after operation by the study group was reduced by 74% from the amount required by the control group (mean, 67 ml vs 256 ml, respectively; P less than .0001). Thirteen percent (13%) of the study group required postoperative homologous blood transfusions, as compared to 39% of the control group (P less than .0001). Additionally, patients in the study group had higher hemoglobin levels beginning on the first postoperative day. This study indicates that a postoperative blood salvage system safely and effectively reduces the amount of homologous blood required and sustains higher hemoglobin levels after operation. PMID- 1875201 TI - Long-term follow-up evaluation of a prototype press-fit knee prosthesis. A. T. Moore's distal femoral resurfacing arthroplasty. AB - Austin T. Moore designed a little-known prototype press-fit distal femoral resurfacing knee prosthesis. The implant's history and its long-term follow-up result in one existing patient are reported in the 51st anniversary year of Dr. Moore's first prosthetic procedure. PMID- 1875202 TI - Knee manipulation following total knee arthroplasty. Analysis of prognostic variables. AB - In an effort to identify prognostic indicators for knee manipulation, the authors retrospectively reviewed the records of 60 osteoarthritic patients with posterior stabilized knee implants who required manipulation (94 knees) between January 1984 and December 1986. They also studied the records of 28 consecutive osteoarthritic patients who were implanted with 41 posterior stabilized knees between January 1985 and September 1985 whose knees did not require manipulation (control group). In both patient groups the following parameters were assessed and compared: overall knee alignment, joint line elevation, anterior to posterior (AP) dimension of the knee, AP placement of the tibial component, patellar height, obesity, age, preoperative flexion, time of manipulation, single vs bilateral knee implants, final flexion, final Hospital for Special Surgery (HSS) score, and the development of heterotopic ossification. The findings of this study showed that an increase in the AP knee dimension by 12% or greater was a critically independent variable that significantly predisposed patients to manipulation. They also show that quadriceps adhesions were another major factor leading to manipulation, and that rupturing of these adhesions led to an increase in heterotopic ossification. This review also indicated that 3 months after knee arthroplasty was a significant time for evaluation because knee flexion and HSS score at this point in the patient's recovery positively correlated with the final HSS score. PMID- 1875203 TI - Prophylactic and early therapeutic use of the Greenfield filter in hip and knee joint arthroplasty. AB - The orthopaedic literature does not provide clear guidelines for the protection of the extremely high-risk thromboembolic patient undergoing hip and knee total joint or related reconstructive surgery. Nor is there agreement of how to protect the immediate postoperative patient with thromboembolic complications. The authors, believing that routine anticoagulation measures are ill-advised in these two circumstances, elected instead to place a Greenfield vena cava filter for prevention of life-threatening thromboembolism. Using prospective selection criteria, 47 patients could be followed over a 24-76-month period. There were no clinical embolic episodes in either group and no late complications of the filter placement. The few complications in this series were related to insertion, only one of which lead to minor long-term disability. The caval patency rate was 96%. The authors have concluded that such prophylactic use of the Greenfield vena cava filter is justified since it contributes to safer and more reliable total hip and total knee surgery with only minor morbidity. PMID- 1875204 TI - Exposure of the hip using a modified anterolateral approach. AB - This report outlines an exposure to the hip using one curved skin incision, permitting retention of the femoral neck, and allowing access to both the anterior and posterior aspects of the hip, the whole of the proximal femur, and the circumference of the acetabulum. This approach is useful in revision surgery. The anterior abductors are mobilized using partial sharp release. A review of postoperative abductor function is presented, demonstrating satisfactory function after partial sharp release. PMID- 1875205 TI - Calcar resorption beneath a well-fitting flanged femoral prosthesis. AB - Forty-three of 51 Link SP hip prostheses inserted 4 years previous to this study were clinically and radiographically reviewed. All demonstrated bone resorption in excess of 2 mm under the collar, but this resorption was not progressive. No prosthesis had loosened. The collar of a prosthesis, even when securely cemented into the femur with a carefully matched neck cut, was decoupled from its functional position in all the reviewed cases at 4 years. Its only remaining function was to prevent subsidence within the cement mantle, should it ever become necessary to provide stability. PMID- 1875206 TI - Postoperative use of continuous passive motion, transcutaneous electrical nerve stimulation, and continuous cooling pad following total knee arthroplasty. AB - Three rehabilitation modalities relating to in-hospital postoperative care following unilateral total knee arthroplasty (UTKA) were studied regarding their effect on pain management and UTKA outcome: (1) continuous passive motion (CPM); (2) CPM with transcutaneous electrical nerve stimulation (TENS); and (3) CPM with continuous cooling pad (CCP). Phase I: CPM. Twenty-two UTKA patients were randomized into two postoperative care groups: (1) 12 with CPM; and (2) 10 with no CPM. Total hospitalization pain medication consumption was significantly less for the CPM group (P less than .05). Phase II: CPM With TENS. Forty-eight UTKA patients were randomized into three postoperative care groups: (1) 18 with an ipsilateral thigh TENS unit delivering sensory threshold stimulation; (2) 18 with a subthreshold TENS unit; and (3) 12 with no TENS unit. All groups used CPM. No significant difference was found regarding pain medication consumption. Phase III: CPM With CCP. Thirty consecutive UTKA patients were divided into two postoperative care groups: (1) 15 with a CCP unit; and (2) 15 with no CCP unit. Both groups used CPM. No significant difference was found regarding total or intramuscular hospitalization pain medication consumption. However, oral hospitalization pain medication consumption was significantly less for the CCP group (P less than .01). This postoperative UTKA study demonstrates significantly decreased total in-hospital pain medication consumption when comparing CPM vs no CPM, significantly decreased oral in-hospital pain medication consumption when comparing CPM with CCP vs CPM without CCP, but no difference when comparing CPM with TENS vs CPM without TENS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875207 TI - Efficacy of intraoperative autotransfusion in primary total hip arthroplasty. AB - The role of intraoperative autotransfusion in diminishing perioperative transfusion requirements was studied in 64 patients undergoing primary total hip arthroplasty. The total transfusions administered in a 3-day perioperative period were tabulated for the study group (in which intraoperative autotransfusion was utilized) and compared to that of the control group. Despite the use of the Cell Saver autotransfusion device, no significant difference was noted between the total units of blood transfused perioperatively in the two groups. Moreover, calculations of mean perioperative blood loss (intra- and postoperative) were not significantly different, nor was there any difference in mean hemoglobin concentrations between the two groups on the third postoperative day. All 64 patients received 4 units or less of banked blood in the perioperative period. The authors conclude that this modality of blood conservation is not necessary in primary hip arthroplasty and that a well planned autologous prebanking program should be sufficient in the vast majority of cases to avoid the use of banked homologous blood. PMID- 1875208 TI - Capsular impingement as a source of pain following bipolar hip arthroplasty. AB - Concerns regarding the extent and predictability of pain relief with bipolar hemiarthroplasty have been raised. Inconsistent clinical results have been reported, with persistent postoperative groin pain noted in some patients. A diverse number of bipolar operative techniques have been reported, but discussion of the surgical treatment of capsular tissue has usually been omitted. Although the source of postoperative pain is difficult to determine, the authors report the relief of groin pain after a capsulectomy in a patient with a preexisting bipolar hemiarthroplasty, thus offering one possible etiology. PMID- 1875209 TI - Influence of prosthetic joint line position on knee kinematics and patellar position. AB - Prosthetic joint line position after total knee arthroplasty (TKA) was investigated using sagittal roentgenograms obtained from six fresh frozen cadaver knees. A specially designed knee testing device was developed that allowed for a controlled flexion angle while maintaining a constant quadriceps force. Pre- and postoperative roentgenograms were obtained from 30 degrees to 120 degrees in 15 degrees intervals. Steinman pins inserted into the medial femoral condyle and patella were used as reference points in the roentgenograms. A displacement vector between the medial femoral condyle and tibial plateau was used to analyze the tibiofemoral joint relationship. The functional patellar length (Insall Salvati ratio), was used to determine correct patellar height. Another displacement vector was used to measure the patellofemoral joint relationship, and the angle between the patellar cut surface and femoral long axis was also calculated. Bone resection thickness from the femoral, tibial, and patellar surfaces was equal to the prosthetic thickness. This reconstructive scheme produced correct ligament balance and flexibility of the knee without the aid of tensioning devices or special measurements. Patellar tracking appeared to be identical before and after surgery. This accurate but simple surgical technique also reproduced normal knee extensor mechanisms that may influence longevity and long-term results of TKA. PMID- 1875211 TI - Ceramic head implantation failures. PMID- 1875210 TI - Treatment of acutely infected arthroplasty with local antibiotics. AB - The authors have identified 22 patients with acutely infected total joint arthroplasties, 9 hips, and 13 knees. Following organism identification and assessment of the patients' general medical condition, the patients were treated with an implantable antibiotic pump. This allowed the delivery of a high concentration of antibiotic solution to a localized area. Systemic levels of antibiotic were kept to a minimum, thereby eliminating potential serious side effects of antibiotic treatment. Local concentrations were extremely high, exceeding the minimal inhibitory concentration (MIC) in all cases by 8-10-fold. Twenty patients have been followed for 30 months, and of these, 17 patients are considered to be infection free. There were three failures. The organisms that have been treated have been gram negatives, gram positives, and some mixed infections. Results are encouraging with this form of treatment, and additional patients are continually being added to the study. PMID- 1875212 TI - A simple and effective method of sterilizing Esmarch bandages. AB - The authors evaluated three methods of sterilizing Esmarch bandages. A commercially available autoclave tape laid along the whole length of the midpoint of the width of the bandage was used to determine sterility. Satisfactory sterility was achieved by rolling the Esmarch loosely, with a standard crepe bandage interposed between layers. Tightly rolled bandages and folded bandages without the crepe bandage interposition could not be reliably sterilized. PMID- 1875213 TI - Range of motion in contemporary total hip arthroplasty. The impact of modular head-neck components. AB - The prosthetic range of motion (PROM) of two modular total hip arthroplasty (THA) systems and one older nonmodular comparison system was evaluated. The head-neck geometry of the modular systems resulted in a smaller PROM than the nonmodular system. Longer head-neck components commonly had flanges, which caused the greatest reduction in PROM. This effect became more pronounced as head size decreased. Modular head-neck components offer recognized benefits but can be associated with notably smaller ROM and increased risk of prosthetic impingement. The surgeon should be aware that in modern systems PROM decreases when neck width is increased. Moreover, in cases of prosthetic instability the potential role of the flange of a modular head should be evaluated. Methods are suggested for maximizing PROM clinically through preoperative planning, optimal femoral neck resection, and implant utilization. PMID- 1875214 TI - Polymerase chain reaction: the molecular microscope of residual disease. PMID- 1875215 TI - Organ preservation in bladder carcinoma: a matter of selection. PMID- 1875216 TI - The significance of circulating cells carrying t(14;18) in long remission from follicular lymphoma. AB - Peripheral blood mononuclear cell fractions from 15 patients in continuous clinical remission from follicular lymphoma for longer than 10 years were examined for cells carrying the t(14;18) translocation using the polymerase chain reaction (PCR). The assay used was able to detect one positive cell in approximately 5 x 10(5) cells (a single 14q+ molecule in 2.5 micrograms DNA). Cells positive for t(14;18) were found in six of eight patients initially presenting with stage III or IV disease, compared with zero of seven of those with stage I or II disease (P less than .05). In two cases 14q+ junction regions were also successfully amplified from formalin-fixed biopsy material obtained at presentation 12 and 17 years previously. In both, sequence analysis demonstrated that the cells circulating in remission belonged to the original clone. These results indicate that cells bearing t(14;18) frequently persist in the peripheral blood in long remission of advanced follicular lymphoma and question the value of their presence as a predictor of relapse. PMID- 1875217 TI - Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy. AB - Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials. PMID- 1875218 TI - Allogeneic bone marrow transplantation as therapy for primary induction failure for patients with acute leukemia. AB - The survival of patients with acute leukemia who do not achieve a remission with primary therapy is very poor. High-dose chemoradiotherapy followed by allogeneic bone marrow transplantation (BMT) has been shown to be effective therapy for patients with acute and chronic leukemia. Therefore, we determined the long-term disease-free survival of patients who did not achieve a remission and were then treated with high-dose therapy and bone marrow allografting from matched sibling donors. Twenty-one patients (median age, 28 years) who did not achieve a remission with induction chemotherapy were subsequently treated with allogeneic BMT. After BMT, 90% achieved a complete remission. Six died of complications of the therapy, and six patients relapsed between 27 and 448 days after BMT. Nine patients (43%; median age, 25 years) are alive between 556 and 4,174 days after BMT. The cumulative probability of disease-free survival at 10 years is 43%. This study suggests that allogeneic BMT can be an effective therapy to achieve long term control of acute leukemia, even in those patients who do not achieve a remission with primary therapy. PMID- 1875219 TI - Importance of bone marrow cytogenetic evaluation before autologous bone marrow transplantation for Hodgkin's disease. AB - Alkylating agents used either with or without radiation therapy have been associated with the development of myelodysplastic syndrome (MDS) and acute nonlymphoblastic leukemia (ANLL) after treatment of both malignant and nonmalignant disorders. This report describes seven patients with recurrent Hodgkin's disease (HD) evaluated for bone marrow transplantation (BMT) who developed chromosomal abnormalities, and emphasizes the importance of bone marrow cytogenetic studies before bone marrow harvest. Three patients with histologically normal bone marrow underwent autologous BMT and subsequently developed an MDS or ANLL. Four patients had the clonal abnormality detected before bone marrow harvest and did not proceed to BMT. PMID- 1875220 TI - Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: prolonged survival and preservation of cognitive function. AB - Combination chemotherapy with or without radiotherapy has had only modest efficacy in the treatment of primary CNS lymphoma. Median survival of these patients, treated primarily with radiotherapy, is 13 months; 5-year survival is less than 5%. Thirty consecutive non-acquired immune deficiency syndrome patients with primary CNS lymphoma were treated with barrier-dependent chemotherapy using intraarterial mannitol to open the blood-brain barrier (BBB). Follow-up included extensive neuropsychologic testing of all patients. Thirteen patients received cranial radiation 1 to 9 months before referral (group 1). Seventeen patients received initial BBB disruption chemotherapy with subsequent radiation only for tumor progression or recurrence (group 2). The difference in median survivals from diagnosis--17.8 months for group 1 and 44.5 months for group 2--was statistically significant (P = .039). Group 1 survival is comparable with the 20 month median survival of a historical series of patients (n = 208) treated with radiotherapy with or without chemotherapy. Group 2 patient survival represents an advance in the survival of CNS lymphoma and was associated with preservation of cognitive function in six of seven nonirradiated complete responders observed for 1 to 7 years. Patient toxicity was manageable in this intensive therapeutic regimen. In this series, a plateau in survival curves suggests that a major portion of these patients may be cured without the neuropsychologic sequelae associated with cranial radiation. PMID- 1875221 TI - Impact of autologous bone marrow infusion on hematopoietic recovery after high dose cyclophosphamide, etoposide, and cisplatin. AB - Because of potential tumor contamination and inadequacy of current purging technique of bone marrow in patients with solid tumors, we investigated an alternative approach to high-dose therapy without autologous bone marrow (ABM) infusion. Three levels of nonmyeloablative doses of cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 165 mg/m2 (CVP) were administered to patients with metastatic solid tumors. Patients were randomized to ABM (n = 46) or no-ABM (NABM) (n = 46) infusion after CVP to study the impact of ABM on hematopoietic recovery, morbidity, and mortality. All patients had ABM harvested, underwent conventional chemotherapy, and then received CVP. Seventy three patients received two courses of similar doses. The following were the median days to absolute neutrophil count (ANC) of 0.1 x 10(9)/L: for the ABM arm, 19, 21, and 19 and for the NABM arm, 23, 20, and 21 at levels 1, 2, and 3, respectively, during course 1 (P = .01, .80, and .01, respectively). During course 2, ANCs to 0.1 x 10(9)/L and 0.5 x 10(9)/L were attained significantly faster at levels 1 and 3 in the ABM arm. ANC to 1.0 x 10(9)/L was comparable in both arms. Incidence of infection and duration of fever were similar in both arms. Although mortality and the incidence of delayed hematopoietic recovery were more frequent in the NABM arm, this was not statistically significant. Platelet recovery was consistently prolonged in course 2 in both arms, with demonstrable benefit of ABM in course 2 when dose levels were collectively considered. We conclude that (1) ABM enhanced recovery of ANC to 0.1 x 10(9)/L; (2) ABM did not decrease the incidence of infections and the duration of fever; and (3) CVP can be safely given without ABM to carefully selected patients. PMID- 1875222 TI - Prognosis in T2N0M0 stage I breast carcinoma: a 20-year follow-up study. AB - In a study of prognosis in node-negative breast carcinoma, we investigated 293 T2N0M0 patients treated by mastectomy and axillary dissection with a median follow-up of 19.8 years. The probability of surviving 20 years considering all causes of death was 41.3% +/- 3.0%. Recurrence-free survival (Kaplan-Meier estimate) was 68.6% +/- 3% at 10 years and 63.2% +/- 3.1% at 20 years. The estimated probability of cure determined by the method of Brinkley and Haybittle was 63% (95% confidence interval [Cl], 55% to 72%). Prognosis was related to primary tumor size with the best separation (P = .06) when tumors from 2.1 to 3.0 cm (33% chance of recurrence at 20 years) and from 3.1 to 5.0 cm (44% chance of recurrence at 20 years) were compared. The histologic tumor type was prognostically important. Recurrence at 20 years was not significantly different for patients with invasive duct (34%) and lobular (42%) carcinoma. Women with special types (medullary, mucinous, papillary, etc) of carcinoma had a 25% chance of recurrence. Subsequent contralateral breast carcinoma was diagnosed in 29 patients, and four of these were fatal, accounting for only 4.6% of breast carcinoma deaths. Thirty-two patients (10.9%) developed a nonmammary malignant neoplasm (NMMN) after the ipsilateral breast carcinoma, and 69% of these lesions were fatal. Although the chances of recurrence at 20 years related to tumor size and type did not differ statistically in the series, there were trends that suggest that T2N0M0 patients can be stratified into recurrence risk groups based on tumor size and histologic type. These factors should be taken into consideration in the design and analysis of clinical adjuvant therapy trials. Measures for the early detection of common NMMNs should be included in the routine follow-up of T2N0M0 breast carcinoma patients. PMID- 1875223 TI - Integration of conservative surgery, radiotherapy, and chemotherapy for the treatment of early-stage, node-positive breast cancer: sequencing, timing, and outcome. AB - The optimal means of combining breast-conserving surgery, radiation therapy, and chemotherapy for the treatment of patients with early-stage, node-positive breast cancer is not known. We reviewed the results in 295 patients treated at the Joint Center for Radiation Therapy and affiliated institutions from 1976 to 1985. All patients had positive axillary nodes on dissection, had no gross residual disease in the breast or axilla after surgery, and received breast irradiation (with or without nodal irradiation) and three or more cycles of a cyclophosphamide, methotrexate, and fluorouracil (CMF)-based or doxorubicin-containing regimen. Median follow-up in patients without any failure was 78 months. Breast failure rates were assessed in relation to the sequencing of radiotherapy and chemotherapy. The different sequences were not randomly assigned, and the characteristics of the sequence groups differed. The actuarial 5-year breast failure rate was 4% in 99 patients receiving radiotherapy before chemotherapy; 8% in 54 patients sequentially receiving some chemotherapy, then radiotherapy without concurrent chemotherapy, then further chemotherapy; and 6% in 116 patients receiving concurrent chemotherapy and radiotherapy. However, the failure rate was 41% in 26 patients who received all chemotherapy before radiotherapy. The crude incidences of local failure within 4 years of treatment in these groups were 3%, 2%, 4%, and 15%, respectively (P = .065 for all four groups not being the same). The actuarial 5-year local failure rate was 5% for 252 patients irradiated within 16 weeks after surgery compared with 35% for 34 patients irradiated more than 16 weeks after surgery. The 4-year crude incidences were 4% and 12% for the two groups, respectively (P = .06). These results suggest that delaying the initiation of radiotherapy may result in an increased likelihood of local failure. Formal randomized controlled trials will be needed to confirm these results and to improve the integration of these treatment modalities. PMID- 1875224 TI - Lack of efficacy of high-dose leucovorin and fluorouracil in patients with advanced pancreatic adenocarcinoma. AB - Leucovorin potentiates the cytotoxicity of fluorouracil (5-FU) in experimental tumor systems and appears to enhance the effectiveness of 5-FU in patients with colon cancer. Twenty-two eligible patients (18 previously untreated) with advanced pancreatic adenocarcinoma were treated in a phase II trial of leucovorin 500 mg/m2/d for 6 days by continuous intravenous infusion with 5-FU 370 mg/m2/d by rapid intravenous injection on 5 consecutive days, beginning 24 hours after initiation of leucovorin infusion. Among the 20 assessable patients, there were no complete or partial regressions, although there was one minor response lasting 4 months. Three patients had stable disease for 5, 20, and 21 months, respectively. Median survival was 10 weeks. Toxicity was predominantly mucosal; stomatitis grade 2 or worse was seen in five patients, and diarrhea grade 2 or worse was seen in four. Hospitalization for toxicity was necessary in four previously untreated patients and three previously treated patients. The median WBC nadir was 4.6 (range, 1.4 to 9.6) x 10(3)/microL, and the median platelet nadir was 147.0 (range, 69.0 to 240.0) x 10(3)/microL. This combination of leucovorin and 5-FU did not demonstrate meaningful therapeutic activity in patients with adenocarcinoma of the pancreas and was associated with moderate to severe toxicity. It should not be considered a standard treatment for patients with this disease. PMID- 1875225 TI - Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma: a multicenter phase II study. AB - Twenty-five assessable patients with metastatic melanoma have been entered in a multicenter phase II study of two induction cycles of human recombinant interleukin-2(IL2), 18 x 10(6) IU/m2/d continuous intravenous (IV) infusion on days 1 to 5 and days 12 to 17. Dacarbazine (DTIC), 850 mg/m2 IV bolus was given on day 26. The cycle was repeated at 5 weeks. Maintenance therapy was scheduled 3 weeks after the completion of induction treatment, consisting of IL2, 18 x 10(6) IU/m2/d for 5 days alternating with DTIC, 850 mg/m2 IV every 3 weeks, for a total of 18 weeks. Six patients responded (24%); two complete and four partial. Stable disease was seen in five patients. None of the six patients with more than two sites of metastases responded. Maximum response was observed in the first 3 months of treatment. Progression-free periods of 6 months and longer were seen in the two complete responders (8 and 17+ months), in two of the four partial responders (7 and 12+ months), and in three of the five patients with stable disease (9+, 15, and 17+ months). Toxicity included fever, skin rash, fatigue, anorexia, and diarrhea in most patients. Two patients had a weight gain of more than 10%. Eight patients needed intensive care for the observation and treatment of a myocardial injury (one patient), ventricular tachycardia (one), hypotension and oliguria (four), and sepsis (two). Sequential treatment with IL2 and DTIC appears to be effective but not clearly better than could be expected of IL2 alone. PMID- 1875226 TI - Calculating dose intensity. PMID- 1875227 TI - Levamisole and melanoma. PMID- 1875228 TI - Dose-intensity analysis and randomized trials. PMID- 1875229 TI - Antimicrobial contact activity of econazole sulfosalicylate. AB - The aim of this investigation was to compare the contact action of econazole sulfosalicylate (E-SSA) on mycetes (Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, Trichophyton rubrum, T. cutaneum, Pityrosporum sp.), Gram positive bacteria (Staphylococcus aureus, Streptococcus faecalis) and Gram negative bacteria (Escherichia coli, Citrobacter freundii) with that exerted by econazole nitrate (E-NIT). The results show E-SSA activity greater than E-NIT (in particular against mycetes and Gram-negative bacteria). The E-SSA contact activity trials illustrated certain properties of this imidazole sulfosolicylate such as: absence of latency time, antimicrobial activity proportional to its concentration, when a high concentration is used, given the limiting influence of pH and ionic strength of the medium. The higher E-SSA contact activity, in relation to E-NIT, can be correlated to its greater lipophylia considering also the lipophylic properties of SSA and the scarce dissociation of E-SSA. PMID- 1875230 TI - Comparative efficacy of cefotetan and clindamycin plus amikacin as antimicrobial prophylaxis for major head and neck surgery. AB - A total of 41 patients were randomly allocated to receive either cefotetan (total dose, 20 g) or clindamycin (total dose, 12 g) plus amikacin (total dose, 5 g) as perioperative antimicrobial prophylaxis for major head and neck surgery. The two groups were similar in age, male to female ratio, stage of cancer, and the various types of surgery. No patient received radiotherapy or chemotherapy before surgery. The wound infection rate was 4% in the group of patients receiving cefotetan and 0% in the group receiving clindamycin plus amikacin. No major side effects were observed in either group. On the basis of this study a five-day perioperative course with cefotetan may be considered effective antimicrobial prophylaxis in patients undergoing major head and neck oncologic surgery. PMID- 1875231 TI - Intravenous ciprofloxacin for the treatment of severe infections. AB - Intravenous ciprofloxacin at a daily dosage of 400 mg divided in two doses was administered to 19 patients with severe infections caused by ciprofloxacin susceptible bacteria. These infections included: 11 surgical would infections, 5 soft tissue infections, 2 respiratory tract infections, 1 urinary tract infection. The offending pathogens were: 8 coagulase-negative staphylococci, 3 Staphylococcus aureus, 3 Pseudomonas aeruginosa, 2 Proteus spp., 1 Escherichia coli, 1 Branhamella catarrhalis, 1 Klebsiella ozenae and 1 Serratia liquefaciens. Overall, 17 of 19 infections (89%) showed a satisfactory clinical response to trial therapy (15 cures and 2 improvements). Microbiological eradication was observed in 17 out of 20 isolated pathogens. Emergence of resistance to ciprofloxacin occurred in 1 coagulase-negative Staphylococcus and was associated with clinical failure. No side effects were observed. We conclude that intravenous ciprofloxacin may represent efficacious and safe therapy of severe infections; however close microbiological monitoring seems to be necessary to evaluate the emergence of resistance during quinolone therapy. PMID- 1875232 TI - 5-Fluorouracil, epirubicin and cyclophosphamide (FEC combination) in advanced breast cancer. AB - Thirty patients with advanced breast cancer, not pretreated with chemotherapy for advanced disease, received a polychemotherapy regimen containing 5-fluorouracil (500 mg/m2 iv), epirubicin (50 mg/m2 iv) and cyclophosphamide (500 mg/m2 iv) every four weeks. All patients were evaluable for response and for toxicity. No complete remissions were observed, while 13 patients (43.5%) achieved a partial remission for a median duration of 46 weeks. The main side-effects were alopecia (grade 2-3 in 57%), leukopenia (grade 3-4 in 33%) and nausea/vomiting (grade 3-4 in 27%). In three cases we observed laboratory signs of cardiotoxicity without clinical symptoms. PMID- 1875233 TI - Skull, patella and thigh cryptococcosis after a crashing injury of the temporal bone. AB - An unusual case of triple location (skull, patella and thigh) Cryptococcus neoformans is described. The peculiarity of the case is based on the probability of direct post-traumatic bone inoculation, subsequent seeding from skull to patella, thigh and cerebral spinal fluid (CSF), patella involvement, lack of evidence of lung involvement and lack of predisposing underlying disease. The response to surgery and a combination of amphotericin B and 5-flucytosine administration was favorable without relapse at follow-up after 7-year discontinuation of therapy. PMID- 1875234 TI - A retrospective view of beta-lactamases. AB - The discovery of a penicillinase (later shown be a beta-lactamase) 50 years ago in Oxford came from the thought that the resistance of many Gram-negative bacteria to Fleming's penicillinase might be due to their production of a penicillin-destroying enzyme. The emergence of penicillinase-producing staphylococci in the early 1950s, particularly in hospitals, raised the question whether the medical value of penicillin would decline. The introduction of new semi-synthetic penicillins and cephalosporins in the 1960s began to reveal many beta-lactamases distinguishable by their different substrate profiles. In this period it was established that genes encoding beta-lactamases from Gram-negative bacilli could be carried from one organism to another on plasmids and also that penicillin inhibited a transpeptidase involved in bacterial cell wall synthesis. During the last two decades a number of these enzymes have been purified and the genes encoding them have been cloned. Much has now been learned, with the aid of powerful modern techniques, about their structures, their active sites, their relationship to penicillin-sensitive proteins in bacteria and to their likely evolution. Further knowledge may contribute to a more rational approach to chemotherapy in this area. Experience suggests that a need for new substances will continue. PMID- 1875235 TI - Beta-lactamase: lessons in the art of survival. AB - 1. A beta-lactamase molecule is a marvelous device enabling its marker to thrive in a hostile and potentially lethal environment. What is more, the protective effect is extended to otherwise vulnerable organisms, securing their survival in the sheltered neighborhood. Curiously, such environmental implications had no discernible impact on the strategy of antibacterial chemotherapy. Moreover, traditional diagnostic routines are largely responsible for the sheltered survival of susceptible pathogens. 2. For half a century, since their existence was discovered by Abraham and Chain, beta-lactamases have never ceased to amaze us with an ever-widening spectrum of structural and functional variants, appearing in increasingly rapid succession in an ever broader range of bacteria. Whereas the phenomenon itself was the predicted outcome of unguarded expansion of beta-lactam therapy, its scope is a testimony to the unique advantage of an otherwise irrelevant, and thus freely modifiable and transmissible, enzyme as a key to survival. 3. Perhaps the least expected lesson is to be had from the adaptive behaviour of the beta-lactamase molecule itself. Faced with virtually countless structural variations on the beta-lactam theme, nearly all created so as to frustrate its function, the beta-lactamase molecule proves to be so versatile in overcoming so many of its potential inhibitors that it makes us reflect on the evolutionary significance of coping and survival at the molecular level. PMID- 1875236 TI - Transient state kinetic studies on catalysis and inhibition of staphylococcal beta-lactamase. AB - The interaction of beta-lactamase with a beta-lactam substrate may, in addition to hydrolysis of the beta-lactam by way of an acylenzyme intermediate, lead to transient or permanent inhibition through one or more branches in the catalytic pathway. The balance between these processes depends on the interplay between the chemical reactivities of interacting groups and on effects on protein conformation and stability but the molecular basis is not fully understood. Examples of physical and kinetic probes of some of the mechanisms are discussed. PMID- 1875237 TI - Some molecular properties of Citrobacter diversus beta-lactamases. AB - Citrobacter diversus ULA-27, a clinical isolate showing a broad resistance pattern towards both penicillins and cephalosporins, produces chromosome encoded beta-lactamases. However, the strain remains susceptible to some cephamycins, imipenem, ceftazidime and tetracyclines. Crude bacterial extracts analyzed by isoelectric focusing on polyacrylamide gels, revealed the presence of two main isoforms and some "satellite" bands focusing in the pH range 5.7-7.2. The isoform showing the pIs 6.8 and 6.2 were characterized as class "A" beta-lactamases (according to Ambler's classification) based on the rate of interaction of beta iodopenicillanate and the amino acid sequence around the active site serine. The substrate specificity of the Citrobacter diversus beta-lactamases explains the resistance phenomenon of this bacterium to penicillins and cephalosporins. PMID- 1875238 TI - Penicillin-binding proteins in Streptococcus pneumoniae: alterations during development of intrinsic penicillin resistance. AB - Four out of the five high molecular weight penicillin-binding proteins (PBPs) of Streptococcus pneumoniae are involved in the development of intrinsic penicillin resistance. In beta-lactam resistant laboratory mutants, point mutations in the PBP 2x-genes were identified that result in low penicillin-affinity mutant proteins. In contrast, PBPs 1a, 2x, and 2b of resistant clinical isolates are highly altered as can be recognized biochemically and immunologically; DNA sequence analysis of the PBP 2x gene from resistant strains confirmed these results. The variability of the three PBPs analyzed implies a very heterogeneous gene pool accessible to the pneumococcus that is used for recruitment of resistant PBP genes in wild type strains. PMID- 1875239 TI - Comparison of the effectiveness of various antibiotics in the treatment of methicillin-susceptible Staphylococcus aureus experimental infective endocarditis. AB - The effectiveness of various antibiotics was tested in the eradication of a strain of methicillin-susceptible Staphylococcus aureus (MSSA) of cardiac vegetations, in an experimental model of endocarditis in rabbits. Twelve animals comprised the control group and 48 the treated ones. After inducing the experimental endocarditis, the animals were treated for three days; then mortality, blood cultures at 48 and 72 hours and the title of the colony forming units per gram of vegetation (CFU/g) were evaluated. Imipenem and the cloxacillin gentamicin association were found to be as effective as cloxacillin in eradicating the microorganisms of the vegetation. Clindamycin in high doses was shown to be a valid alternative. Vancomycin, teicoplanin, rifampin and ciprofloxacin were less effective than cloxacillin. The experimental model seems to be an effective method for evaluating antimicrobial treatments in staphylococcal endocarditis. PMID- 1875240 TI - Aztreonam biliary excretion in bile duct ligated jaundiced rats. AB - An experimental study was undertaken to assess aztreonam biliary concentrations in bile duct ligated jaundiced rats. The study proved that aztreonam biliary concentrations are sufficient to inhibit Gram-negative bacteria within the first and the second hour after antibiotic administration. The experimental model suggests that clinical conditions such as lithiasis or neoplasms of the biliary tree should not totally inhibit the antibiotic excretion. PMID- 1875241 TI - Combination-sensitive neurons in the medial geniculate body of the mustached bat: encoding of relative velocity information. AB - 1. Orientation sounds (pulses) emitted by the mustached bat (Pteronotus parnellii) consist of up to four harmonics (H1-4); each harmonic contains a constant frequency (CF) component and a terminal frequency modulated (FM) component, so that there are eight components in total (CF1-4 and FM1-4). By referring the echo from a target to the emitted pulse, the mustached bat derives velocity information from Doppler shift and distance information from echo delay. In this study, the responses of single neurons in the medial geniculate body (MGB) to synthetic biosonar signals were investigated. Stimuli consisted of CF, FM, and CF-FM sounds. Paired CF-FM sounds were used to mimic any two harmonics of pulse-echo pairs. The dorsal and medial divisions of the MGB were found to contain combination-sensitive neurons. These neurons responded poorly to individual sounds regardless of frequency and amplitude and were facilitated by paired sounds presented at particular frequencies, amplitudes and inter-component intervals (simulated echo delay). Combination-sensitive neurons were tuned to the frequencies that characterize particular components of natural biosonar signals and were classified according to the components of pulse-echo pairs that best matched the spectral selectivity of the neuron. Two classes of combination sensitive neurons were found, CF/CF and FM-FM. This paper focuses on CF/CF combination-sensitive neurons, which extract velocity information from paired CF components, and on CF2 and CF3 neurons, which, although not combination sensitive, are tuned to the frequencies of the CF2 and CF3 components of biosonar signals. 2. CF2 and CF3 neurons were sharply tuned in frequency. The best frequencies of the most sharply tuned CF2 neurons were all approximately equal to 61.17 kHz (SD = 370 Hz), which closely matches the frequency at which P. parnellii stabilizes the CF2 component of an echo when compensating for Doppler shift. Thus CF2 neurons are specialized for a fine analysis of Doppler compensated echoes. 3. Tuning curves of CF2 and CF3 neurons remained narrow regardless of stimulus level. When compared at high stimulus levels (30 and 50 dB above minimum threshold), bandwidths of tuning curves of CF2 and CF3 neurons were much smaller than those of peripheral auditory neurons turned to CF2 or CF3 frequencies but were about the same as those of cortical neurons tuned to CF2 or CF3 frequencies. Thus the sharpening of neural tuning curves by the bat's central auditory system occurs within or before the MGB.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1875242 TI - Response of joint capsule neurons to axial stress and strain during dynamic loading in cat. AB - 1. Experiments were conducted to test the hypothesis that the responses of joint capsule mechanoreceptors better encode tissue stress or tissue strain. The experimental model was a small ligament from the cat knee capsule, which was stretched uniaxially in vitro. Experiments were done with either force or displacement as the controlled variable, and with steps, sinusoids, or pseudorandom Gaussian noise (PGN) as the input function. 2. The strength of coupling between neural discharge and both strain and stress was quantified during step experiments using linear correlation coefficients. The correlation between the frequency of neural discharge and stress was 0.93 +/- 0.09 (SD). The correlation between frequency of neural discharge and strain was -0.91 +/- 0.06. The magnitudes of these correlation coefficients were not significantly different. 3. The strength of coupling between neural discharge and both strain and stress during sinusoidal and PGN experiments was quantified by the use of an information theoretic statistic, transinformation. Out of 282 sinusoidal runs, transinformation between neural discharge and stress was significantly greater than transinformation between strain and neural discharge 241 times. Transinformation between strain and neural discharge was significantly greater 15 times. 4. During PGN experiments, transinformation between stress and neural discharge was greater than transinformation between strain and neural discharge in all 19 experimental runs. 5. Conditional transinformation between strain and neural discharge, given stress, was calculated for all sinusoidal and pseudorandom experiments. This statistic was greater than zero in 268 out of 289 experimental runs, indicating that a component of strain independent of stress is being signaled in the neural discharge. PMID- 1875243 TI - Sensitivity of MST neurons to optic flow stimuli. I. A continuum of response selectivity to large-field stimuli. AB - 1. Neurons in the dorsomedial region of the medial superior temporal area (MSTd) have large receptive fields that include the fovea, are directionally selective for moving visual stimuli, prefer the motion of large fields to small spots, and respond to rotating and expanding patterns of motion as well as frontal parallel planar motion. These characteristics suggested that these neurons might contribute to the analysis of the large-field optic flow stimulation generated as an observer moves through the visual environment. 2. We tested the response of MSTd neurons in two awake monkeys by systematically presenting a set of translational and rotational stimuli to each neuron. These 100 X 100 degrees stimuli were the motion components from which all optic flow fields are derived. 3. In 220 single neurons we found 23% that responded primarily to one component of motion (planar, circular, or radial), 34% that responded to two components (planocircular or planoradial, but never circuloradial), and 29% that responded to all three components. 4. The number of stimulus components to which a neuron responded was unrelated to the size or eccentricity of its receptive field. 5. Triple-, double-, and single-component neurons varied widely in the strength of their responses to the preferred components. Grouping these neurons together revealed that they did not form discrete classes but rather a continuum of response selectivity. 6. This continuum was apparent in other response characteristics. Direction selectivity was weakest in triple-component neurons, strongest in single-component neurons. Significant inhibitory responses were less frequent in triple-component neurons than in single-component neurons. 7. There was some indication that the neurons of similar component classes occupied adjacent regions within MSTd, but all combinations of component and direction selectivity were occasionally found in immediate juxtaposition. 8. Experiments on a subset of neurons showed that the speed of motion, the dot density, and the number of different speed planes in the display had little influence on these responses. 9. We conclude that the selective responses of many MSTd neurons to the rotational and translational components of optic flow make these neurons reasonable candidates for contributing to the analysis of optic flow fields. PMID- 1875244 TI - Sensitivity of MST neurons to optic flow stimuli. II. Mechanisms of response selectivity revealed by small-field stimuli. AB - 1. In these experiments we examined the receptive field mechanisms that support the optic flow field selective responses of neurons in the dorsomedial region of the medial superior temporal area (MSTd). Our experiments tested the predictions of two hypotheses of optic flow field selectivity. The direction mosaic hypothesis states that these receptive fields contain a set of planar direction selective subfields that match the local directions of motion within optic flow fields. The vector field hypothesis states that these receptive fields are uniquely sensitive to distributed properties of planar, circular, or radial optic flow fields. 2. Experiments using large-field stimuli revealed that some neurons showed changes in optic flow field selectivity depending on the position of the stimulus in the receptive field; these are position-dependent responses. However, other neurons maintained the same optic flow field selectivities in spite of changes in stimulus position; these are position-invariant responses. We have used the position dependence or invariance of optic flow field selectivity as a way of testing the direction mosaic and vector field hypotheses. Position dependence is more consistent with the direction mosaic hypothesis, whereas position invariance is more consistent with the vector field hypothesis. 3. To test for position effects, we examined the optic flow field selectivity of small subfields within the large receptive fields of 160 MSTd neurons. First, we centered small-field optic flow stimuli of various sizes over the same position in the receptive field. Most MSTd neurons showed decreasing response amplitude with decreasing stimulus size but maintained optic flow field selectivity. 4. We then placed small-field stimuli at various positions within the large receptive field of these MSTd neurons. Position-invariant response selectivity was most prominent in single-component neurons, suggesting that they were more consistent with the vector field hypothesis. Position-dependent response selectivity was most prominent in triple-component neurons, suggesting that they were more consistent with the direction mosaic hypothesis. However, the variations in planar direction preference throughout the receptive field of these triple component neurons were not consistent with a direction mosaic explanation of the large-field circular or radial selectivity observed. 5. Small-field position studies also demonstrated the existence of zones within the receptive field in which either direction-selective inhibitory or direction-selective excitatory responses predominated. The degree of overlap between these zones increased from nonselective to triple- to double- and finally to single-component neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1875245 TI - Fastigial nucleus activity in the alert monkey during slow eye and head movements. AB - 1. Single units were recorded extracellularly from the fastigial nucleus of three macaque monkeys. Two untrained animals were subjected to whole-body yaw rotations in the light and dark and to full-field horizontal optokinetic stimuli provided by a drum with vertical stripes. The third also was subjected to sinusoidal yaw rotations but, in addition, was trained to follow a small spot, which moved in various ways relative to the animal, to reveal possible smooth pursuit and vestibular sensitivities. 2. On the basis of their responses to vestibular and optokinetic stimuli and their responses during smooth pursuit, fastigial neurons could be divided functionally into a rostral and a caudal group. 3. Most rostral neurons exhibited an increased firing for contralateral head rotations and ipsilateral optokinetic stimuli. A few had the opposite combination of directional preferences. The average firing rates increased monotonically both with contralateral head velocity and ipsilateral drum velocity and decreased monotonically for the oppositely directed movements. There was no change in firing rate for either spontaneous saccades or smooth pursuit of a small moving spot. 4. In contrast, neurons in the caudal fastigial nuclei not only have a robust vestibular sensitivity, but respond during smooth pursuit as well. Most discharge during contralateral head velocity and contralateral smooth pursuit so that they exhibit very little modulation during the vestibuloocular reflex (VOR) or when the rotating animal is fixating a target stationary in the world (SIW). The remaining neurons discharge during contralateral head rotations but ipsilateral eye rotations; these units exhibit their greatest modulation during the SIW condition. 5. Because they respond during quite different behavioral situations, it seems likely that rostral fastigial neurons are involved with descending control of the somatic musculature, whereas the caudal neurons are involved in oculomotor control. The sparse anatomic and lesion data that is available is consistent with this idea. PMID- 1875246 TI - Coding the sweet taste in the nucleus of the solitary tract: differential roles for anterior tongue and nasoincisor duct gustatory receptors in the rat. AB - 1. A variety of chemicals that humans describe as sweet drive neurons in the nucleus of the solitary tract (NST) of the rat more vigorously when applied to the taste receptors associated with the nasoincisor ducts (NID) than when applied to taste receptors on the anterior tongue (AT). 2. The differential effects of sweet stimuli applied to the AT and NID also are evident in the set of across neuron correlations produced by these stimuli. The psychophysical similarity among the sweet stimuli is better accounted for by responses to stimulation of the NID than by responses to stimulation of the AT (mean correlation between pairs of sweet stimuli = +0.70 for the NID, +0.44 for the AT). 3. Disaccharides or polysaccharides of glucose, i.e., maltose (0.3 M) and Polycose (0.1 M), are poor stimuli on the NID, evoking responses only 17.8 and 26.7% as great as the response elicited by sucrose (0.3 M), an optimal stimulus for this receptor subpopulation. This suggests that Polycose and maltose interact with receptor sites distinct from those with an affinity for sweet stimuli. Polycose and maltose also are ineffective stimuli on the AT, evoking responses only 11.8 and 4.9% as large as the response evoked by an optimal stimulus for this receptor subpopulation, a mixture of electrolytes (0.3 M NaCl, 0.03 M HCl, and 0.01 M quinine HCl). 4. The relative effectiveness of the sweet sugars in driving NST neurons (sucrose greater than fructose greater than glucose) correlates with their order of effectiveness in generating preference behavior in the rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875247 TI - Individuated finger movements of rhesus monkeys: a means of quantifying the independence of the digits. AB - 1. Two rhesus monkeys were trained to perform flexion and extension movements of each digit of the right hand and of the wrist. Movements of all five digits and the wrist were monitored simultaneously. During each instructed movement, the instructed digit (or wrist) had the greatest excursion; other, noninstructed digits moved to varying degrees. 2. To assess the degree of independence of the different digits during these movements, I plotted, as a function of the instructed digit's position, the position of each noninstructed digit. The resulting trajectories typically were linear, with consistent slopes from trial to trial. 3. The slopes of these noninstructed digit versus instructed digit trajectories were used to calculate an individuation index for each instructed movement and a stationarity index for each digit. These indexes quantified two different aspects of independence. The individuation index reflects the degree to which other digits remained still during instructed movement of a given digit. The stationarity index reflects the degree to which a given digit remained still whenever it was a noninstructed digit. 4. In accordance with casual observation, thumb flexion and wrist flexion and extension consistently had both high individuation and stationarity and therefore can be said to be independent of the fingers. Although the same cannot be said of the other fingers, the present analysis provides a means of quantifying the degree of independence of these digits as well. 5. Factors are discussed that might contribute to the motion of noninstructed digits and to the trajectory linearity. PMID- 1875248 TI - Regional cerebral blood flow during voluntary arm and hand movements in human subjects. AB - 1. Regional cerebral blood flow (rCBF) was measured using positron emission tomography in six normal volunteers while at rest and while performing four different repetitive movements of the right arm. 2. The four movements were performed in random order and consisted of abduction of the index finger, making a fist, sequential thumb to digit opposition, and shoulder flexion. All the movements were done at the same rate, using an auditory cue and involved displacements through similar amounts of the physiological range at each joint. 3. Increases in rCBF were interpreted as evidence of local neural activation and all four movements were associated with significant increases in CBF in the contralateral sensorimotor and premotor areas and in the supplementary motor area (SMA). 4. The average increase in blood flow in the contralateral sensorimotor cortex was significantly greater for the shoulder movement (31%) than for the three other movements. The increases with finger opposition (21%) and fist-making (24%) were not significantly different, and both were significantly greater than with index finger movement (13%). These data indicate that neither "fractionation" nor distal movement per se cause selective activation of sensorimotor cortex. 5. Significantly greater increases in blood flow in both the contralateral premotor cortex and the SMA ("nonprimary motor areas") occurred with shoulder movement than with the other movements. Because this difference may be related to the significantly greater activation occurring concurrently in the sensorimotor cortex, this finding does not prove unequivocally a "selective" role of the nonprimary motor areas in proximal movement. 6. Neither of the two nonprimary motor areas showed selective activation when a simple sequence of finger movements was performed compared with repetitive contractions of the same fingers. 7. Shoulder movement alone was associated with significant increases in rCBF in the ipsilateral sensorimotor cortex (10%), the superior vermis of the cerebellum (19%), and Brodmann areas 5 and 40 in the contralateral hemisphere. 8. The average location of the center of excitation in the sensorimotor cortex and SMA differed for the four movements and was interpreted as evidence of within limb somatotopy. The shoulder focus lay highest in the sensorimotor cortex and lowest in the SMA. PMID- 1875249 TI - Mechanical and electromyographic responses to stretch of the human ankle extensors. AB - 1. During maintained ankle extension with background torques ranging from 0 to 70 N.m, the ankle extensors were stretched by a 5 degree rotation of the ankle joint. Maximal stretch velocity was 170 degrees/s. Regression analysis of simultaneous measurements of total torque and needle and surface electromyograms (EMG) from the soleus and gastrocnemius muscles showed that the soleus muscle generates about two-thirds of the maximal torque (approximately 120 Nm) with the subjects in sitting position. In addition, it was found that there is considerable cross talk between the soleus and gastrocnemius muscles when EMGs are recorded by surface electrodes. 2. The soleus EMG response to stretch began with a "phasic" response (latency 41 +/- 4 ms, mean +/- SD), consisting of two peaks, labeled M1 and M2. The phasic response ended 120-140 ms after stretch onset and was followed by a period of reduced EMG activity, ending at 170-210 ms. After this "silent period," a smaller "tonic" response was seen. The phasic responses of the soleus muscle were much larger than the corresponding responses in the anterior tibial muscle. In contrast, the tonic responses were comparable in the soleus and anterior tibial muscles. 3. The amplitudes of the phasic M1 and M2 responses were independent of the level of the background contraction. This disagrees with the "automatic gain principle," according to which the amplitudes of M1 and M2 should increase proportionally with the background EMG. In contrast to the phasic responses, the amplitude of the tonic EMG response, measured 200 400 ms after stretch onset, followed the automatic gain principle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875250 TI - The raccoon lateral cervical nucleus: a single-unit analysis. AB - 1. Properties of 90 lateral cervical nucleus (LCN) neurons responsive to light tactile stimulation of ipsilateral body surfaces were examined in pentobarbital sodium-anesthetized raccoons. Peripheral receptive fields (RFs) of 60 of these lay totally or partially on glabrous skin of the forepaw. There were 71 neurons antidromically activated from the contralateral thalamic ventro-basal complex (VB) or medial lemniscus. Results were compared with previous findings in the raccoon spinocervical tract (SCT) and the dorsal column-medial lemniscal system (DC-MLS). 2. RFs located on glabrous skin of the digits were significantly smaller than those located on glabrous skin of the palm. All RFs, whether on glabrous skin of the forepaw or elsewhere, tended to be larger than those of either SCT or DC-MLS neurons. LCN units with glabrous forepaw RFs tended to be located ventrally within the nucleus. 3. Of those LCN neurons for which the RFs lay totally or partially on glabrous skin of the forepaw, relative numbers that were rapidly adapting (RA; 77%) versus slowly adapting (SA; 23%) were comparable with those found in the SCT and in VB. Relative numbers of LCN neurons that were classed as light touch (87%) versus multireceptive (13%) were comparable with those found in the SCT. 4. In contrast to both the SCT and VB, but in common with the prethalamic DC-MLS, indentation velocity coding functions of both RA and SA units fell within homogeneous groupings, power function exponents for RA units tending to be steeper than those for SA units (range of b = 0.710 - 0.919 vs. 0.448 - 0.883). 5. It is concluded that the raccoon spinocervicothalamic system (SCTS) as a whole lacks the "modality and place specificity" associated with the DC-MLS. Although the SCTS probably makes significant contributions to properties of VB neurons, these properties primarily reflect those of neurons of the DC-MLS. PMID- 1875251 TI - Saccadic burst neurons in the oculomotor region of the fastigial nucleus of macaque monkeys. AB - 1. The discharge of 255 neurons in the fastigial nuclei of three trained macaque monkeys was investigated during visually guided saccades. Responses of these neurons were examined also during horizontal head rotation and during microstimulation of the oculomotor vermis (lobules VIc and VII). 2. One hundred and two units were characterized by bursts of firing in response to visually guided saccades. Ninety-eight of these (96.1%) were located within the anatomic confines of the fastigial oculomotor region (FOR), on the basis of reconstruction of recording sites. During contralateral saccades, these neurons showed bursts that preceded the onset of saccades (presaccadic burst), whereas, during ipsilateral saccades, they showed bursts associated with the end of saccades (late saccadic burst). They were hence named saccadic burst neurons. Sixty-one saccadic burst neurons (62.2%) were inhibited during microstimulation of the oculomotor vermis with currents less than 10 microA. 3. All saccadic burst neurons were spontaneously active, and the resting firing rate varied considerably among units, ranging from 10 to 50 imp/s. The tonic levels of activity did not correlate significantly with eye position. 4. The presaccadic burst started 18.5 +/- 4.7 (SD) ms (n = 45) before the onset of saccades in the optimal direction (the direction associated with the maximum values of burst lead time, number of spikes per burst, and burst duration). Optimal directions covered the entire contralateral hemifield, although there was a slightly higher incidence in both horizontal and upper-oblique directions in the present sample. The duration of the presaccadic burst was highly correlated with the duration of saccade (0.85 less than or equal to r less than or equal to 0.97). 5. The late saccadic burst was most robust in the direction opposite to the optimal in each unit (the nonoptimal direction). Its onset preceded the completion of ipsilateral saccade by 30.4 +/- 5.9 ms. The lead time to the end of saccade was consistent among different units and was constant also for saccades of various sizes. Thus the late saccadic burst started even before the saccade onset when the saccade duration was less than 30 ms. Unlike the presaccadic burst, its duration was not related to the duration of saccade. 6. Discharge rates of saccadic burst neurons were correlated neither to eye positions during fixation nor to the initial eye positions before saccades. 7. Eye-position units and horizontal head-velocity units were located rostral to the FOR.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1875252 TI - Long-term potentiation of thalamic input to the motor cortex induced by coactivation of thalamocortical and corticocortical afferents. AB - 1. Intracellular recordings were obtained from neurons in the motor cortex (MCx), in which excitatory postsynaptic potentials (EPSPs) were evoked by microstimulation of the somatosensory cortex (SCx) and the ventrolateral nucleus (VL) of the thalamus. The effects of combined tetanic stimulation of SCx and VL on the amplitudes of these EPSPs were studied. 2. Amplitudes of both corticocortical (CC) and thalamocortical (TC) EPSPs were potentiated after combined tetanic stimulation. This potentiation occurred exclusively in neurons that were located in the superficial layers (II/III) and that received direct input from both the SCx and VL, with both inputs synapsing in close proximity to each other. In all cases, the potentiation lasted until the electrode went out of the cell (21 +/- 25 min, mean +/- SD) the longest being 90 min. We therefore refer to this potentiation as long-term potentiation (LTP). 3. Tetanic stimulation of the thalamus only did not produce LTP in neurons receiving direct input from the VL. 4. LTP was not induced in either CC or TC EPSPs in neurons located in layer V and/or in neurons receiving long-latency CC EPSPs. 5. It is concluded that TC input from the VL to the MCx is potentiated only when coactivated with the CC input from the SCx. PMID- 1875253 TI - Recruitment of crab gastric mill neurons into the pyloric motor pattern by mechanosensory afferent stimulation. AB - 1. The gastropyloric receptor (GPR) cells are stretch-sensitive muscle receptors in the crab stomatogastric nervous system that use both 5-hydroxytryptamine (serotonin) and acetylcholine as cotransmitters. Brief stimulation of these afferent neurons causes two gastric mill neurons to be recruited into the pyloric motor pattern. 2. The GPR cells evoke complex synaptic potentials in the lateral gastric (LG) and medial gastric (MG) motor neurons, two component neurons of the gastric mill central pattern generator. When the gastric mill is quiescent (as often happens in vivo), GPR stimulation transiently inhibits LG and MG. After this transient inhibition, these cells undergo a prolonged excitation during which they fire bursts of action potentials at a constant phase relation to the pyloric motor pattern. 3. To determine the causes for this effect, we examined the effects of GPR stimulation on these two cells and on the inferior cardiac motor neuron, which is electrically coupled to them. When GPR is stimulated, all three cells receive rapid biphasic synaptic potentials that are blocked by nicotinic antagonists, followed by a slow, prolonged depolarizing potential. 4. The slow, prolonged depolarizing potential is not blocked by nicotinic or muscarinic cholinergic antagonists but is mimicked and occluded by exogenously applied serotonin. 5. The prolonged excitation, mediated at least in part by serotonin, may be responsible for the recruitment of the gastric mill neurons into the pyloric motor pattern. Thus sensory input can directly exert prolonged modulatory effects that change the functional cellular composition of pattern generating circuits. PMID- 1875254 TI - Taste-responsive neurons of the glossopharyngeal nerve of the rat. AB - 1. Taste sensibilities of neurons in mammalian glossopharyngeal nerves have been inadequately studied, although they innervate the majority of taste buds and may provide unique taste information. 2. Extracellular responses of glossopharyngeal neural units to taste stimuli infused into foliate or vallate papillae were recorded in anesthetized rats. A 0.3-ml/min infusion of stimuli into papillae resulted in short-latency, 5-s nerve-impulse rates that approached 10 times the response rates observed using less invasive means of stimulation. 3. Sucrose, Na saccharin, NaCl, NH4Cl, KCl, HCl, citric acid, acetic acid, MgSO4, and quinine.HCl were effective stimuli for glossopharyngeal neurons at concentrations that have behavioral significance. 4. Response spectra for individual neural units with either foliate or vallate receptive fields fell into three clusters. Forty-six percent were A units that responded most strongly to acids and chloride salts, NH4Cl being the most effective; neither quinine nor sucrose was effective. Twenty-three percent were S units that responded to sugars and saccharin; quinine, salts, and acids were not effective. Thirty-one percent were Q units that responded to quinine; neither NaCl, HCl, nor sucrose was effective stimulus for these fragile units. 5. Glossopharyngeal A neural units were more sensitive to 1 mM HCl than were electrolyte-sensitive H units of the chorda tympani, although both respond generally to salts and acids. Units relatively specific for sodium salts (N units), which are common in the chorda tympani nerve, were not found in the glossopharyngeal nerve, which explains losses in sodium-specific behavior after cutting only the chorda tympani nerve. 6. Q units were the only glossopharyngeal neural units that responded significantly to quinine, and units with similar response spectra do not occur in the chorda tympani nerve. Q units probably mediate aversive reflexes to quinine that are eliminated by cutting only the glossopharyngeal nerve. Glossopharyngeal S neural units were more sensitive to sucrose and are more common than their counterparts in the chorda tympani, although it is not known how they might compare with sugar-sensitive units in the greater superficial petrosal nerve. 7. These data strongly suggest that posterior taste bud fields innervated by the glossopharyngeal nerve are specialized for functions different from those of anterior taste bud fields innervated by the facial nerve. PMID- 1875255 TI - Neuronal activity related to saccadic eye movements in the monkey's dorsolateral prefrontal cortex. AB - 1. Single-neuron activity was recorded from the prefrontal cortex of monkeys performing saccadic eye movements in oculomotor delayed-response (ODR) and visually guided saccade (VGS) tasks. In the ODR task the monkey was required to maintain fixation of a central spot throughout the 0.5-s cue and 3.0-s delay before making a saccadic eye movement in the dark to one of four or eight locations where the visual cue had been presented. The same locations were used for targets in the VGS tasks; however, unlike the ODR task, saccades in the VGS tasks were visually guided. 2. Among 434 neurons recorded from prefrontal cortex within and surrounding the principal sulcus (PS), 147 changed their discharge rates in relation to saccadic eye movements in the ODR task. Their response latencies relative to saccade initiation were distributed between -192 and 460 ms, with 22% exhibiting presaccadic activity and 78% exhibiting only postsaccadic activity. Among PS neurons with presaccadic activity, 53% also had postsaccadic activity when the monkey made saccadic eye movements opposite to the directions for which the presaccadic activity was observed. 3. Almost all (97%) PS neurons with presaccadic activity were directionally selective. The best direction and tuning specificity of each neuron were estimated from parameters used to fit a Gaussian tuning curve function. The best direction for 62% of the neurons with presaccadic activity was toward the contralateral visual field, with the remaining neurons having best directions toward the ipsilateral field (23%) or along the vertical meridian (15%). 4. Most postsaccadic activity of PS neurons (92%) was also directionally selective. The best direction for 48% of these neurons was toward the contralateral visual field, with the remaining neurons having best directions toward the ipsilateral field (36%) or along the vertical meridian (16%). Eighteen percent of the neurons with postsaccadic activity showed a reciprocal response pattern: excitatory responses occurred for one set of saccade directions, whereas inhibitory responses occurred for roughly the opposite set of directions. 5. Sixty PS neurons with saccade-related activity in the ODR task were also examined in a VGS task. Forty of these neurons showed highly similar profiles of directional specificity and response magnitude in both tasks, 13 showed saccade-related activity only in the ODR task, and 7 changed their response characteristics between the ODR and VGS tasks.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1875256 TI - Trochlear unit activity during ocular convergence. AB - 1. Ocular convergence is usually accompanied by excyclotorsion of the eyes. Furthermore, the magnitude of cyclotorsion is dependent on the elevation of the eyes. The reason for this excyclotorsion during convergence is not understood. 2. Excyclotorsion could be produced by either increased activity in the inferior oblique muscle or decreased activity in the superior oblique muscle. An earlier study indicated that convergence may also be accompanied by a temporal (lateral) translation of the eye. This observation is more consistent with a relaxation of the superior oblique than contraction of the inferior oblique. 3. This hypothesis was tested by recording the activity of 31 neurons in the trochlear nucleus, which contains the superior oblique motoneurons. This was done in alert monkeys that were trained to make both versional and vergence eye movements. In addition, the cyclotorsion associated with convergence was measured in one of these monkeys. 4. A consistent excyclotorsion associated with convergence was observed. Trochlear unit activity decreased during convergence in all cells tested. The magnitude of this decrease was significantly greater than that seen with conjugate adduction. Furthermore, the size of the decrease varied systematically with ocular elevation in a manner that was consistent with earlier measures of cyclotorsion during convergence. 5. These results suggest that the excyclotorsion seen during convergence, and perhaps the lateral translation of the eye, are due to a relaxation of the superior oblique muscle. This relaxation during convergence is greater than that which accompanies similar conjugate movements of the eyes. We hypothesize that this peculiar pattern of muscle innervation has a motor rather than sensory function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875257 TI - Behavior of upper cervical inspiratory propriospinal neurons during fictive vomiting. AB - 1. The role of upper cervical inspiratory (UCI)-modulated neurons in respiratory muscle control during vomiting was examined by recording the impulse activity of these neurons during fictive vomiting in decerebrate, paralyzed cats. Fictive vomiting was identified by a characteristic series of bursts of coactivation of phrenic and abdominal muscle nerves, elicited either by electrical stimulation of supradiaphragmatic vagal nerve afferents or by emetic drugs, which would be expected to produce expulsion of gastric contents in nonparalyzed animals. 2. Data were recorded from 43 propriospinal UCI neurons, located in the C1-C3 spinal segments near the border of the intermediate gray matter and lateral funiculus, which were antidromically activated with floating pin electrodes placed in the ipsilateral lateral funiculus, usually at T1-T3. Some cells (9/21 tested) were also activated from the upper lumbar cord (L1). During respiration, most neurons (n = 40) had an augmenting discharge pattern during inspiration. In addition, more than one-half (55%) fired tonically during the remainder of the respiratory cycle. About 40% of UCI neurons showed variations in their firing pattern during the noninspiratory portion of respiration. These latter two properties of UCI neurons were not observed in dorsal and ventral respiratory group (DRG and VRG-, respectively) bulbospinal inspiratory (I) neurons previously recorded under similar conditions. 3. During fictive vomiting, the firing pattern of most UCI neurons fell into one of three main categories. More than one-half (53%) were active in phase with bursts of phrenic discharge and were thus classified as Active-type cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875258 TI - Attempts to physiologically classify human thenar motor units. AB - 1. This study was designed to determine whether human thenar motor units can be classified into types by the same physiological criteria used for other mammalian limb motor units and to consider whether such classification is functionally relevant. 2. Contractile responses of 25 human thenar single motor units were examined when their motor axons were stimulated intraneurally at rates from 1 to 100 Hz and intermittently at 40 Hz in a conventional 2-min fatigue test. Twitch and tetanic forces were measured together with various indexes of contractile rate. 3. Twitch contraction times and subtetanic to maximum tetanic force ratios were both distributed continuously. "Sag" in tension was not evident in unfused force profiles. Thus these units could not be divided into fast and slow types by the use of traditional contractile rate criteria. 4. Most units were fatigue resistant, with force fatigue indexes (FI) ranging from 0.33 to 1.14. None could be classified as fatiguable (FI less than 0.25). Seven units (28%) fell into the fatigue-intermediate (FI = 0.25-0.75) category, whereas 18 units (72%) had FI greater than 0.75, i.e., they were fatigue-resistant units. However, these units could not be classified by conventional FI and contractile rate criteria, because fatigue-resistant and fatigue-intermediate units had similar contractile rates. 5. Additional FI were calculated to describe changes in contractile rate. During the fatigue test, units behaved in one of three ways, showing 1) little change in either force or rate; 2) contractile slowing during the contraction and relaxation phases, with little or no force loss; or 3) both force and rate reduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875259 TI - Force-frequency relationships of human thenar motor units. AB - 1. Force-frequency relationships were examined in 30 human thenar single motor units. The technique of intraneural stimulation was used to stimulate the motor axon in the median nerve proximal to the elbow with a tungsten microelectrode. 2. The stimulation consisted of either single shocks or trains of pulses (1 or 2 s duration) at constant rates varying between 5 and 100 Hz. To control various mechanical artifacts, the stimuli were delivered after electronically resetting the force baseline, and the stimuli were phased to the pulse pressure wave. Thumb flexion and abduction force components were recorded and the magnitude and direction of the resultant force calculated. Electromyographic responses (EMG) were recorded from both the proximal and distal thenar muscle surfaces. 3. For all units, twitch force began to fuse between 5 and 8 Hz and maximum tetanic force was achieved between 30 and 100 Hz. Half-maximum tetanic force was produced at 12 +/- 4 (SD) Hz, as assessed by interpolation using the nearly linear force frequency relationship between 8 and 30 Hz (on logarithmic frequency coordinates). 4. For the majority of units (n = 19), the strongest force changes in response to variations in stimulation frequency occurred between 5 and 10 Hz (sensitivity 6 +/- 1 mN/Hz). Fewer units showed highest force-frequency sensitivity between 8 and 15 Hz (n = 7; 4 +/- 3 mN/Hz) or 10 and 20 Hz (n = 4; 5 +/- 2 mN/Hz).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875260 TI - Morphology and axonal projection patterns of individual neurons in the cat perigeniculate nucleus. AB - 1. The lateral geniculate nucleus is the primary thalamic relay through which retinal signals pass en route to cortex. This relay is gated and can be suppressed by activity among local inhibitory neurons that use gamma-aminobutyric acid (GABA) as a neurotransmitter. In the cat, a major source of this GABAergic inhibition seems to arise from cells of the perigeniculate nucleus, which lies just dorsal to the A-laminae of the lateral geniculate nucleus. However, the morphological characteristics of perigeniculate cells, and particularly the projection patterns of their axons, have never been fully characterized. We thus examined the morphology of these cells: individually by intracellular injection of horseradish peroxidase (HRP) and en masse with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHAL). 2. We recorded from 12 perigeniculate cells that we impaled and successfully labeled with HRP. These cells exhibited response properties generally consistent with those described previously. They had long response latencies to stimulation of the optic chiasm and relatively large, often diffuse, receptive fields. The visually evoked responses of most of the cells were dominated by one eye. Compared with cells of the lateral geniculate nucleus, perigeniculate cells had large somata (517 +/- 136 microns 2 in cross-sectional area, mean +/- SD), which were fusiform or multipolar in shape, and dendritic arbors that extended a considerable distance (1,095 +/- 167 microns) parallel to the border between the perigeniculate and lateral geniculate nuclei. Terminal arbors of some dendrites were quite complex and beaded. 3. The axons of six perigeniculate cells were labeled sufficiently well to trace and reconstruct over a considerable distance. Each of these axons formed branches that descended to innervate the lateral geniculate nucleus, and this geniculate innervation was exclusively limited to the A-laminae. Terminal boutons within the A-laminae were nearly all en passant, which gave the axons a beaded appearance. Furthermore, branches of five of these six axons provided local innervation of the perigeniculate nucleus, generally within each labeled cell's own dendritic arbor. Three of the cells also exhibited an axon branch that extended medially and caudally away from the soma, but we were unable to trace these axon branches to their targets. 4. Within the lateral geniculate nucleus, each arbor of perigeniculate axons derived from two main components. One was a narrow, sparse medial component that innervated laminae A and A1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1875261 TI - Behavioral deficits induced by local injection of bicuculline and muscimol into the primate motor and premotor cortex. AB - 1. The role of intracortical GABAergic inhibition in the performance of hand movements was studied in macaque monkeys while they performed two behavioral tasks: a raisin pick-up test and a visual reaction-time task. A gamma aminobutyric acid (GABA) agonist, muscimol (MUS; 1-5 microgram), and an antagonist, bicuculline methiodide (BMI, 1-10 micrograms), were injected at various sites in the precentral motor cortex (MC), at which single-unit activity was related to the manual aspects of the performance of the reaction-time task. 2. Manual dexterity in the raisin pick-up task was severely disturbed by injections of either MUS or BMI into the hand MC. The effect was less severe after injections into the postarcuate premotor cortex (PM). 3. Performance of the reaction-time task was unstable after injection of BMI. The instability was caused by increased electromyogram (EMG) activity and by cocontractions of agonistic and antagonistic muscles of the arm during the pressing or release of the lever. 4. Reaction time was increased by injection of MUS, although the effect was temporary and decayed within 60 min. These deficits were consistent with the time course of the decrease in the total amount of EMG activity of hand muscles related to the task. As in the case of the raisin pick-up task, performance deficits were greater when MUS and BMI were injected into the hand MC and smaller when they were injected into the PM. 5. After injection of BMI, the animals gradually began to display muscle activity in response to a green warning signal that did not require a behavioral response. The muscle activity accelerated to spontaneous muscle twitches without any external stimulus, and the animals were unable to continue the task. These BMI-induced twitches were eliminated by injection of barbiturate. 6. Appropriate levels of GABAergic inhibition in the MC appear, therefore, to be important for the regulation of spatiotemporally organized ensembles of muscle activity, in particular for reciprocal contraction at the task-related joints. PMID- 1875262 TI - Intracellular study of electrophysiological features of primate spinothalamic tract neurons and their responses to afferent inputs. AB - 1. Intracellular recordings were made from 43 spinothalamic (STT) neurons in the lumbosacral region of the spinal cord in anesthetized macaque monkeys. The antidromic responses of these neurons to electrical stimulation of the ventral posterior lateral (VPL) nucleus of the thalamus were examined, and orthodromic responses to electrical stimulation of the sural nerve or to mechanical stimulation of hindlimb skin were recorded to study the electrophysiological features of these neurons and their responses to afferent inputs. 2. The resting membrane potential of the neurons ranged from -26 to -70 mV and the antidromic latency from 2.3 to 9.1 ms. Three of the neurons were located in lamina 1 and were recorded so briefly that only antidromic and spontaneous activity could be studied. The rest of the neurons were located in laminae III-V and were of the wide-dynamic-range (WDR) type. 3. The antidromic action potentials recorded in the somas of STT neurons typically showed a fast rising phase and a short initial segment-somadendritic (IS-SD) delay. After repetitive antidromic stimulation, a progressive elongation of the IS-SD delay, widening of the spike, and failure of the SD spike were observed. 4. The afterpotential of the antidromic action potential consisted of a fast afterhyperpolarization (AHPf) and sometimes a delayed depolarization (DD) and a slow afterhyperpolarization (AHPs). The amplitude and the duration of the AHPs were progressively increased when longer trains of stimuli were used. When the membrane potential was hyperpolarized, the amplitude of the AHPs decreased, suggesting an involvement of K+ and/or Cl- ions. However, the AHPs completely disappeared when the strength of stimulation was adjusted to a level just below the threshold for the axon, suggesting that it was unlikely that recurrent inhibition contributed to the AHPs. 5. The background activity of 32 STT neurons was analyzed. The membrane potential at which spikes were triggered in these neurons was around -42 mV. The width and the rise time of the spontaneous spikes were shorter than those of antidromic action potentials, although the maximum rate of rise was similar. The heights of the spontaneous spikes were slightly shorter than those of antidromic action potentials. 6. Three types of background activity have been observed. One type had a very low average spontaneous rate with a bursting firing pattern, consisting of a few spikes superimposed on a depolarization. This type of activity was seen mostly in lamina I neurons. The second type of activity had a moderate to high spontaneous rate with a fairly constant interval between spikes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1875263 TI - Two forms of inhibition of spinothalamic tract neurons produced by stimulation of the periaqueductal gray and the cerebral cortex. AB - 1. Recordings were made from the lumbosacral spinal cord in anesthetized macaque monkeys. The inhibitory effects of electrical stimulation of the periaqueductal gray (PAG) and the cerebral cortex or cerebral peduncle (CP) were tested and compared by recording 1) cord dorsum potentials evoked by stimulation of the sural nerve, 2) discharges recorded extracellularly, and 3) membrane potentials recorded intracellularly from spinothalamic tract (STT) neurons at rest (background activity) or in response to stimulation of the sural nerve. 2. Stimulation of the cortex or in the CP preferentially reduced the amplitude of the N1 and N2 waves of the cord dorsum potential evoked by stimulation of the sural nerve, without affecting the N3 wave. Stimulation of the PAG, on the other hand, reduced the amplitude of the N3 wave with little effect on the N1 and N2 waves. 3. The activity of 62 STT neurons was recorded extracellularly. Stimulation of the PAG or the cortex/CP inhibited nonpreferentially the responses of the neurons in the superficial laminae to all afferent inputs. On the other hand, stimulation of the PAG or the cortex/CP inhibited preferentially the responses of most STT neurons in deep layers of the dorsal horn to the small or large afferent input, respectively. 4. Thirty-five neurons were recorded intracellularly. The membrane potential of the neurons averaged -45.5 +/- 10.1 (SD) mV. All neurons were recorded in laminae III-VI; the neurons were of the wide-dynamic-range (WDR) type and had background activity. 5. The inhibitory effects of stimulation of the PAG were tested on all 35 neurons. In 32 of the neurons, stimulation of the PAG evoked a hyperpolarization. The background activity of the neurons was reduced (generally it completely ceased) by the hyperpolarization. In three neurons stimulation of the PAG did not evoke a hyperpolarization and the background activity of the neurons did not change. Nevertheless, the responses of these three neurons to afferent input were inhibited by stimulation in the PAG. 6. The inhibitory effects of stimulating the cortex and/or the CP were tested in 26 of the 35 neurons. Stimulation of the cortex and/or the CP evoked a hyperpolarization in all the neurons, although, in 10 of the 26 neurons, stimulation of the CP also evoked a depolarization. The hyperpolarization generally blocked the background activity of the neurons. 7. The effective stimuli in the PAG and the cortex/CP to evoke a hyperpolarization in STT neurons were short, high-frequency trains of pulses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1875264 TI - Dependence of discharge rate on sound pressure level in cochlear nerve fibers of the alligator lizard: implications for cochlear mechanisms. AB - 1. Rate-level functions for individual cochlear nerve fibers of the alligator lizard, Gerrhonotus multicarinatus, were generated by measuring a fiber's driven discharge rate (the difference between the average discharge rates in the presence and absence of a tone burst) as a function of sound pressure level. 2. When plotted in double logarithmic coordinates, the rate-level function approaches a straight line at low sound pressure levels and saturates at high levels. Thus the rate-level function is a saturating power function of sound pressure. We developed an algorithm to estimate the exponent of the straight-line portion of the function. When tested on simulated data with known parameters, the algorithm provided unbiased estimates of the exponent. 3. Nerve fibers innervating two distinct regions of the alligator lizard's auditory organ, the free-standing region and the tectorial region, have differing rate-level functions. 4. The mean exponent estimate of the rate-level functions of fibers innervating the free-standing region is approximately 2 at all frequencies. For stimulus frequencies at the characteristic frequency (CF), the mean value was 2.1 +/- 0.10 (SE, n = 131). For stimulus frequencies above and below CF, the mean exponent estimates were 2.1 +/- 0.13 (n = 49) and 2.1 +/- 0.11 (n = 34), respectively. A value of 2 is expected for a broad class of nonlinear systems. 5. The mean exponent estimates of the rate-level functions of fibers innervating the tectorial region were 3.0 +/- 0.30 (n = 32) for stimulus frequencies at CF, 2.5 +/- 0.33 (n = 3) for stimulus frequencies below CF, and 1.0 +/- 0.21 (n = 16) for stimulus frequencies above CF. Both the deviation from square-law behavior at CF and the frequency dependence of the exponent imply that nonlinear processing in the tectorial region differs intrinsically from that in the free-standing region. 6. For free-standing fibers, the saturation rate of the rate-level function (the maximum driven rate) is independent of stimulus frequency. This suggests that, in the free-standing region, 1) the alternating (AC) component of the receptor potential makes no significant contribution to the average rate of discharge and 2) neural saturation results from a process that occurs after the narrow-band frequency-selective process(es). 7. In tectorial fibers, the saturation rate is a bandpass function of sound frequency, with a broad peak between 150 and 300 Hz. This function appears to be common to all tectorial fibers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1875265 TI - Changes in central delay of soleus H reflex after facilitatory or inhibitory conditioning in humans. AB - 1. Central delay (CD) changes after facilitatory or inhibitory conditioning of the soleus H reflex have been investigated in a group of normal subjects as a function of the conditioning and test stimulus intensities and also as a function of the Hmax/Mmax ratio. Both facilitation and inhibition of the reflex response have been obtained by conditioning stimulation of the ipsilateral tibial nerve at suitable conditioning-test stimulus intervals. CD changes have been extrapolated from the variations of the time interval between afferent and efferent neural volleys underlying the H reflex, directly recorded from the sciatic nerve. 2. The CD was significantly decreased by facilitatory and increased by inhibitory conditioning. Facilitatory CD changes were positively related to test stimulus strength (at a given conditioning stimulus intensity) and negatively related to conditioning stimulus strength (at a given test stimulus intensity). Both trends were reversed after inhibitory conditioning. The effectiveness of facilitatory conditioning was positively related to the individual Hmax/Mmax ratio whereas a negative relationship could be observed after inhibitory conditioning. 3. Also, the "conditioning threshold" (the minimal conditioning stimulus strength affecting the reflex size) and the "maximal conditioning effect" (the conditioning stimulus intensities leading to either the saturation of the facilitatory effect or the suppression of the reflex response) were significantly related to the Hmax/Mmax ratio. 4. We suggest that temporal changes in the H reflex pathway after facilitatory or inhibitory conditioning stimuli depend both on the size of the motoneuronal pool underlying the reflex response, as determined by the test stimulus intensity, and on the individual excitability of the motoneuronal pool, as defined by the Hmax/Mmax ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875266 TI - Preceptor teaching strategies: behaviors that facilitate role transition in senior nursing students. AB - This article describes the learning outcomes of students who participated in a senior preceptorship course. Data from student logs and course evaluations forms were analyzed descriptively to identify the specific instructional strategies of preceptors that were instrumental in teaching students the roles and functions of the staff nurse. Role modeling was one of the most effective strategies and also the one regarded by preceptors as least significant. PMID- 1875267 TI - Stages in the development of a needs assessment questionnaire. AB - This article describes the stages in the development of a questionnaire for use in a large-scale needs assessment study as the basis for a staff development program. While a considerable literature exists on questionnaire design in general, we emphasize the need for a conceptual framework behind the questionnaire, proceeding from analysis of the objectives of the needs assessment and guiding both the construction of variables and the reduction and analysis of the questionnaire's data. PMID- 1875268 TI - Relocation. An educational challenge. AB - Moving! The word evokes thoughts of chaos, disorder, and stress. In this article, the authors describe their experience in designing and providing educational programs to facilitate the relocation of an entire hospital to a new facility in a large metropolitan area. PMID- 1875269 TI - The 1990s. A new education-service dichotomy. AB - In the past, the notion of the "education-service dichotomy" concerned the divergent priorities of academia and the clinical care delivery setting. Collaboration has resulted in a great deal of reconciliation between the differing emphases of these two orientations. Recently, a new and possibly more problematic dichotomy of the 1990s presents itself WITHIN the practice setting. This article describes trends that may adversely affect the educational and administrative dynamics internal to the clinical practice setting, suggests changes that must be undertaken in order to bring goals into closer alignment, and gives specific strategies used in one medical center nursing service that have successfully averted a "new dichotomy scenario". PMID- 1875270 TI - A staff development workshop on cultural diversity. AB - In a multicultural society, nurses work with clients from diverse cultural groups. The beliefs, values, and customs of these groups greatly influence the client's response to health care. Nurses need to understand the culture of the client in order to provide competent care. This article describes a process for developing a cultural diversity workshop that allows nurses to develop skills in dealing with clients from diverse backgrounds. Guidelines for identifying workshop content, educational group leaders, and suggestions for workshop evaluation are included. PMID- 1875271 TI - The job aid: a user-friendly, cost-effective tool. PMID- 1875273 TI - A program on the immune system for health care workers. PMID- 1875272 TI - The nursing process applied to staff development. PMID- 1875274 TI - Getting started. AB - Taking the time to address both the internal and external evaluation components for every offering is without a doubt very time consuming. However, with today's focus on quality and cost effectiveness, staff development educators must take the necessary time. Further, the data can often be used to justify continuing programs that administration may want to cut, especially when the external evaluation indicates a significant change in on-the-job performance. PMID- 1875275 TI - Treatment of spider bites by high voltage direct current. AB - Between September 7, 1988, and January 15, 1991, 147 cases of confirmed (19) and suspected spider bites have been treated by high voltage direct current (HVDC) shocks. Venom damage to tissue was arrested at the time of treatment. Pain and systemic symptoms usually improved within 15 minutes. Lesion excision or grafts have not been necessary in any of the 127 cases with completed followup. PMID- 1875276 TI - Geriatric abdominal surgery under local anesthetic: a case report. AB - Abdominal surgery in a fragile elderly patient is often a dilemma, especially in the rural hospital setting where complex anesthesiology services are not available. We have done thyroidectomies and umbilical and inguinal hernias under local anesthesia, and report the following case where the technique was extended to a critically ill geriatric patient with a strangulated hernia. PMID- 1875277 TI - A department comes of age. PMID- 1875278 TI - [Study of components in crude drugs by head space gas chromatography. I. Components of Asiasari radix]. AB - Determinations of volatile components of essential oil contained in Asiasari Radix were studied by head space gas chromatography. The head space gas, which was generated by heating 0.2 g of crude drug with 1.0 ml of water at 90 degrees C for 45 min, was analyzed directly by gas chromatography or gas chromatography mass spectrometry. This method was rapid, and did not require tedious procedures and time consuming, and without contamination of the column. PMID- 1875279 TI - [Studies on early changes in myocardial electrolytes and histological reaction in isoproterenol-induced myocardial injury]. AB - To determine morphological changes in the very early stage of damage and recovery of myocardial fibers in relation to electrolytes and water content in the myocardium, experimental myocardial infarcts were produced after injection of 75 mg/kg isoproterenol (Isp) to rats weighing 270 +/- 10 g. Electrolytes were examined by an atomic absorption spectrophotometer, and histologic examination was performed by light and electron microscopy. At 30 min after Isp injection, Ca and water contents of myocardium increased, but Mg decreased. These myocardial damages showed a maximum level from 6 to 12 h after injection of Isp. It consisted of reversible injury of muscle fibers represented by eosinophilic and fatty degeneration, intermingled with coagulation necrosis of fibers which was irreversible. Most of these eosinophilic degeneration fibers recovered to normal fibers between 12 h and 3 d after the injection. The chronological changes of Ca, Mg, and water contents were well correlated to the morphological early changes of myocardial fibers, and this experimental model by using Isp may be useful for examining the recovery of damaged myocardial tissue and estimating the effects of therapeutics. PMID- 1875280 TI - [Pharmacological studies on leaf of Arctostaphylos uva-ursi (L.) Spreng. III. Combined effect of arbutin and indomethacin on immuno-inflammation]. AB - A study was carried out to examine the combined effect of arbutin isolated from the leaves of Arctostaphylos uva-ursi (L.) Spreng. (Bearberry leaf) and indomethacin on Type IV allergic reaction-induced immuno-inflammation, carrageenin-induced edema and adjuvant-induced arthritis. Contact dermatitis caused by picryl chloride (PC-CD) and sheep red cell delayed type hypersensitivity (SRBC-DTH) was not inhibited by the oral application of arbutin at 2 divided doses immediately before and 16 h after the application, but arbutin at dose of 50 mg/kg 24 h after the application rapidly decreased the swelling of PC-CD. Arbutin (p.o.) plus indomethacin (s.c.) showed inhibitory effect on the swelling of PC-CD and SRBC-DTH stronger than that of indomethacin alone. When arbutin (p.o.) and indomethacin (s.c.) in a given portion were simultaneously administered, the inhibitory effect was more potent than that of indomethacin alone in both carrageenin-induced edema and adjuvant-induced arthritis. These results suggest that arbutin may increase the inhibitory action of indomethacin on PC-CD, SRBC-DTH, carrageenin-induced edema and adjuvant-induced arthritis, but further investigations are required to understand the mechanism involved. PMID- 1875281 TI - The kinetics of flurbiprofen in synovial fluid. AB - Steady state plasma and synovial fluid flurbiprofen concentrations obtained from 26 rheumatoid arthritis patients receiving 100 mg of flurbiprofen b.i.d. were analyzed using the NONMEM program. Only one synovial fluid sample per patient was available. Population estimates for the plasma parameters, clearance, volume of distribution, and elimination half-life were 1.75 L hr-1, 11.9 L, and 4.8 hr, respectively, and the corresponding interindividual variances in these parameters were 29, 19 and 23%, respectively. The apparent elimination half-life from synovial fluid was 7.1 hr. After accounting for interindividual variability there was a residual variability of approximately 40% in both the plasma and synovial fluid concentrations. PMID- 1875282 TI - Theoretical model for both saturable rate and extent of absorption: simulations of cefatrizine data. AB - A pharmacokinetic model incorporating saturable rate of absorption of the Michaelis-Menten type was recently developed to fit cefatrizine (CFZ) plasma concentrations with time following oral administration of 500-mg capsules to humans. This model (MM) was statistically superior to models incorporating either first-order or zero-order absorption. However, the MM model does not predict the reduction in extent of absorption with dose observed in vivo. In this study, a model is proposed in which a time constraint, delta t, is added to the MM model. This new model (MM-delta t) is tested with data following doses of 250, 500, and 1000 mg of CFZ. When delta t is set to 1.5 hr, the predicted relative changes with dose in bioavailability, F, peak plasma concentration, Cmax, the time at which the peak concentration occurs tmax, and the mean absorption time, MAT, are generally in good agreement with the experimental data. The time interval of 1.5 hr is compatible with passage by a limited region within the small intestine where drug is absorbed by a facilitated transport mechanism. Influence of each absorption model parameter (Vmax, Km, and delta t) on total area under the concentration versus time curve (AUC), F, Cmax, and tmax, is assessed by simulation. The MM-delta t model is able to summarize the nonlinerity observed in both rate and extent of absorption. PMID- 1875283 TI - Mathematical model for in vivo pharmacodynamics integrating fluctuation of the response: application to the prolactin suppressant effect of the dopaminomimetic drug DCN 203-922. AB - We propose a general pharmacokinetic-pharmacodynamic model that integrates the rhythmic fluctuation of hormone secretion for the description of the hormone lowering effect of a drug. The mathematical model takes into account the variation in response observed after administration of a placebo and the drug. It is assumed that the change with time in the physiological response during the placebo period results from fluctuations in the concentration of hypothetical endogenous molecules. The mathematical formulation for predicting the response after drug intake is derived assuming competitive interaction of these "molecules" with the active species for binding to receptors. The suggested "fluctuation model" was implemented in order to describe the time course of the prolactin (PRL) plasma level after administration of two oral doses (2.5 and 5.0 mg) of the dopaminomimetic compound DCN 203-922 (DCN) to 9 healthy male subjects. Its performance was compared with that of conventional modeling approaches, in which the circadian changes after placebo are neglected and the hormone baseline is assumed to be constant. The new model provided a better description of the time course of PRL in most subjects. It was used for prediction of the amplitude and duration of the PRL suppressant effect after single and chronic administration of DCN at various dosage regimens as well as after changes in drug absorption. PMID- 1875284 TI - An initial slope method for model structure: independent estimation of the elimination rate constant of a metabolite. AB - A model structure-independent method for calculating the true elimination rate constant of a primary metabolite is presented. It does not require direct metabolite administration and uses data on drug and metabolite blood (plasma) concentrations after a bolus drug input. The method has been tested and compared with the moment method and the area function method using errorless and errant data simulated on the basis of one- and two-compartment models of the metabolite kinetics. In contrast to known methods the proposed method provided exact estimates of the elimination rate constant in the case of errorless data of both one- and two-compartment models. However the estimates are sensitive to random errors in the concentration data. PMID- 1875285 TI - Mean time parameters for generalized physiological flow models (semihomogeneous linear systems). AB - This note gives expressions for recirculation mean time parameters of the disposition kinetics of particles in a semihomogeneous stationary linear system. In such a system each compartment may have an arbitrary single-pass disposition function, rather than a known parametric (usually monoexponential) one. Such systems provide a generalization of physiological flow models. Given observations of arterial blood concentrations and tissue amounts, and making the additional assumptions that (i) the fraction of total blood flow exiting each tissue that goes to each other tissue is constant and known, and (ii) the fraction of drug entering each tissue that is eliminated to the outside is constant and known, the input to each tissue can be known, and therefore both its total blood flow and its single-pass disposition function can be estimated. Recirculation mean time parameters can be computed from these estimates. Application to real thiopental data is presented as an example. PMID- 1875286 TI - Designs for population pharmacodynamics: value of pharmacokinetic data and population analysis. AB - Analyses of simulated data from pharmacokinetic/pharmacodynamic (PK/PD) studies varying with respect to the amount and timing of observations were undertaken to assess the value of these design choices. The simulation models assume mono- or biexponential drug disposition, and Emax-type pharmacodynamics. Data analysis uses a combined PK/PD population analysis or a hybrid, individual-PK/population PD analysis. Assuming that the goal of the PK/PD studies is to estimate population PD, performance of designs is judged by comparing the precision of estimates of population mean PD parameters and of their interindividual variability. The simulations reveal that (i) PK data, even in small number (2 points per person from as few as 25-50% of persons) are very valuable for estimating population PD; (ii) designs involving more individuals, even if many are sparsely sampled, dominate designs calling for more complete study of fewer persons; (iii) the population analysis is generally superior to the hybrid analysis, especially when the PK model is misspecified (biexponential assumed to be monoexponential for analysis); (iv) varying sampling times and doses among subjects protects against the ill effects of model misspecification. In general, the results are quite encouraging about the usefulness of sparse data designs to estimate population dose response. PMID- 1875287 TI - Application of a linear recirculation model to drug targeting. AB - Current interest in drug targeting has inspired theoretical considerations of its potential and problems. Previously, drug targeting has been considered in terms of more or less elaborate compartmental models. The present paper shows how an equivalent analysis of the potential advantage of drug targeting may be derived with the minimum reliance on a specific model. A linear recirculation model is used to describe the drug concentration profile at some target site and in the rest of the body. Equations for the AUCs of drug and of a drug-carrier conjugate can then be derived. These AUCs are used to define a drug targeting index (DTI), a measure of drug targeting selectivity previously derived from a specific model. It is shown that the DTI can be defined solely in terms of extraction ratios for elimination of free drug, when release of drug is confined to the target site. The expression for DTI is shown to be equivalent to that previously derived from several more model-dependent approaches. PMID- 1875288 TI - Comparison and critique of two models for regional drug delivery. AB - A simple stochastic recirculatory formalism is used to compare models of regional drug delivery due to Hunt et al. and Boddy and Aarons. It is shown that these two models are equivalent when regional delivery is ideal. The latter model has the advantage of simplicity. However, the former model appears more useful in relating predictions to experimentally accessible quantities. Neither model is sufficiently general to cover all possible topologies of regions associated with drug response and toxicity. Knowledge of this topology is essential in determining the drug targeting index. The underlying assumptions of the models are discussed, and situations where these assumptions may break down are identified. Finally, it is noted that the analysis of regional delivery may also apply to metabolite and prodrug kinetics. PMID- 1875289 TI - Sesamoidectomy for the treatment of chronic neuropathic ulcerations. AB - Neuropathic ulcerations in diabetic patients are frequent causes of hospitalizations and morbidity. The plantar aspect of the first metatarsophalangeal joint is a common location for these ulcerations, because of the significant weightbearing forces generated through this joint and the presence of sensory and motor neuropathy. The authors describe 24 cases in which excision of the tibial sesamoid, fibular sesamoid, or both, was performed to resolve these lesions. PMID- 1875290 TI - A systematic approach for radiographically evaluating joint disease in the foot. AB - A methodic analysis of foot radiographs is valuable when evaluating for joint disease. The author presents a system that allows the interpreter to establish a list of expected differential diagnoses. This is especially useful when the arthritide does not present with its classic radiographic appearance. PMID- 1875291 TI - Diagnosis of a computer-simulated podiatric patient. AB - The authors discuss the use of computers in medicine. A patient presenting with a condition requiring surgery is represented by a data file in a computer program. The user obtains data from the file by selecting items from a menu. Data are presented on the screen in pop-up windows. By examining the data and making judgments, the user may determine the pathology and make first a provisional and then a definitive diagnosis. PMID- 1875292 TI - Tarsal coalitions. A surgical classification. AB - The surgical alternatives for the treatment of tarsal coalitions include procedures as diverse as arthroplasty and arthrodesis. Traditional classifications of tarsal coalitions are primarily descriptive and afford little information regarding preferred treatment. For this reason, the author introduces the Articular Classification System, which is based on the patient's osseous age, the articular involvement of the coalition, and the associated secondary arthritic changes. This classification system can be used as a framework to discuss recommended surgical procedures and their long-term results. PMID- 1875293 TI - Use of thermography for initial detection of early reflex sympathetic dystrophy. AB - Reflex sympathetic dystrophy is one of a complex of overlapping, sympathetically maintained pain syndromes which are usually initiated by a minor injury that resolves quickly but leaves behind a persistent pain that generalizes to much or all of the limb. The pathophysiology of reflex sympathetic dystrophy is reviewed to show that the pain is accompanied by cooling of the limb, beginning with the distal end and gradually progressing throughout. Thermography is shown to be an effective way to monitor near-surface blood flow in the limbs and to be sensitive to changes accompanying painful conditions. The usefulness of this technique for early detection of reflex sympathetic dystrophy is demonstrated and illustrated with several examples. PMID- 1875294 TI - The effect of various forms of immobilization on plantar foot pressure. AB - In this study, 16 subjects wore different types of immobilization devices while peak pressures on the plantar aspect of the foot were measured using the Electrodynogram (E.D.G.) system. Objective and subjective data were generated and analyzed. Peak pressures decreased on the plantar aspect of the foot as the form of immobilization progressed up the leg. PMID- 1875295 TI - Modification of high-heeled shoes to decrease pronation during gait. AB - One of the reasons that high heels may contribute to the formation of halux valgus is that the wearers pronate during propulsion. This pilot study was performed to determine whether relocation of the heel under the counter of a fashion high-heeled pump could change the degree of pronation of the foot during the gait cycle. The authors report that more foot stability was experienced by the subjects when the center of the heel was offset between 2 and 4 mm medial to the center of the heel counter. This study is designed to promote further research into whether the shoe industry should change the design parameters of high-heeled fashion shoes in order to improve foot function. PMID- 1875296 TI - [The environment: political and ethical issues for human health]. PMID- 1875297 TI - [Deaths associated with methadone]. AB - Used as early as 1946 as an analgesic then to treat heroin addicts, the addicting and toxic potential of methadone was quickly recognized. 25 deaths between 1981 and 1986 were reportedly due to methadone in Geneva of which 2 were violent deaths, 9 were caused by a combination of opiates and methadone and 14 were directly related to methadone. Three deaths were noted during the two first weeks of methadone substitutive therapy. Six were noted less than two weeks before leaving jail and 15 were associated with benzodiazepine ingestion. Postmortem blood levels cannot help determine the severity of poisoning neither a causal relationship between methadone and death. Pathological findings as well as the medical history should be taken into consideration. PMID- 1875298 TI - [Acute poisoning by insecticides with anticholinesterase activity. Evaluation of the efficacy of a cholinesterase reactivator, pralidoxime]. AB - Pralidoxime is the most frequently used antidote in anticholinesterase insecticide poisoning, owing to its cholinesterase reactivating action. The efficiency of Pralidoxime has been retrospectively evaluated by comparing two groups of 31 patients, the first one treated by Pralidoxime in the most commonly used doses (1200mg/24H), the second one untreated. Age, sex and nature of poison were taken in consideration to make a matched distribution in both groups. The clinical and biological initial features were nearly the same in both groups; the other therapeutic measures were the same. There was no statistical difference between the both groups for evolutive criteria such as that mortality, duration of artificial ventilation, intubation, atropine administration, decrease in plasma cholinesterase. The results pleading against the use of Pralidoxime, at least at this dose, in anticholinesterase insecticide poisoning, warrant confirmation by prospective randomized studies. The efficiency of Pralidoxime warrants confirmation firstly in the course of poisonings by some clearly identified insecticides, to which pralidoxime is supposed to be the most effective, cater used in high doses, as recommended by some authors. PMID- 1875299 TI - [Manchineel poisoning. Report of a case]. AB - Clinical signs of poisonings by beach-trees are reviewed following a recent case report. Painful symptoms are the main features owing to the caustic effect of the plant liquid. However the prognosis is usually good. PMID- 1875300 TI - [Inhibition of cytochromes P-450. Biochemical mechanisms and possible therapeutic consequences. I--Inactivation by formation of reversible complexes]. AB - Inactivation of cytochrome P-450 dependent monoxygenases, a major family of hepatic oxidative drug-metabolizing enzymes, has been an area of intensive pharmacological and toxicological investigation. Several classes of drugs are known to be inducers or inhibitors of P-450 isoenzymes. The reversible inhibition of the oxidative microsomal metabolism could be directly related to the ability of the drug to bind cytochrome P-450 as shown by the formation of an inhibitory complex. Such effects result in many drug-drug interactions, affect drug disposition and drug action and could interact with the metabolism of endogenous steroids. This review is concerned primarily with a mechanistic interpretation of the reversible interactions between several classes of therapeutic agents and various P-450 isozymes. The effects of structural modifications on the inhibitory activity were also described. PMID- 1875301 TI - [Air sampling. Why and how?]. AB - The determination of airborne contaminants concentration levels at the workplace is presented as an answer to industrial hygiene problems. A step by step logical method is presented, based upon a preliminary survey as wide as achievable, then the sampling step occurs in order to complete the first assessment. Contaminant exposure, identification of pollution sources and effectiveness of engineering controls can be evaluated by air sampling and analysis. Two field experiences are given as examples (lead and styrene exposures). PMID- 1875302 TI - [Practical application of a strategy of air sampling at the workplace]. AB - Rhone-Poulenc has defined a sampling strategy of the assessment of exposure levels to toxic chemicals at the workplace by inhalation. This strategy is based on the following principles: 1. The exposure measurements must be carried out on carefully selected "homogeneous exposure groups" (HEG). 2. In order to qualify the exposure levels, the strategy specifies a statistical method for estimating the probability of exceeding the professional exposure limit, for a given HEG. 3. Professional judgement is essential in evaluating the risk of professional exposure. PMID- 1875303 TI - [Assessment of exposure to chemical substances in the air at the workplace for comparison with limit values and measurement strategy. Presentation of the work of the European Committee on Normalization in its current state]. AB - After summarizing the various difficulties or uncertainties involved in sampling and measuring procedures at the workplace, two phases to assess workplace exposures are described: an initial appraisal and, when applicable, periodic measurements. The initial assessment includes the identification of potential exposures, the determination of workplace factors, and the assessment of exposures. For exposure measurements, the selection of workers, pattern of sampling and number of samples have to be determined. Conclusions are drawn from the results. PMID- 1875304 TI - [Medical surveillance of people exposed to substances]. AB - Medical surveillance is only one of the ways to estimate the health risk and to assure a good health for workers exposed to atmospheric polluting agents. Occupational practitioner defines himself the forms of this surveillance, according to the risks; excepted a few cases about which legislation determines the minimal contents. Without neglecting clinical exam, in spite of poor and late symptoms, an important place is reserved to biological monitoring: early detection of effects and dosing the product or its metabolites in biological fluids. PMID- 1875305 TI - [Monitoring the air in the workplace. Vapors and gases]. AB - In order to control occupational exposure to gases and vapors, the industrial Hygienist use different sampling instruments and analytical procedures to measure directly or indirectly the gas and vapor concentrations in working atmospheres. The main techniques employed are here described. PMID- 1875306 TI - [Monitoring the air in the workplace: airborne particles]. AB - A good monitoring of the exposition to noxious dusts are dependent on physical factors and regulations. They are reviewed, particularly those issued from the work made by the CEN. The main devices available on the French market are described. PMID- 1875307 TI - When they drink too much. Nursing interventions for patients with disordered water balance. AB - Disordered water balance affects as many as 60% of severely psychiatrically disabled persons. Most patients do not progress to the point of a medical emergency, but are in a state of mild chronic intoxication, making them unavailable for treatment and requiring nursing care to treat the effects of the chronic intoxicated state. Interventions depend on the severity of the disordered water balance and vary from teaching fluid intake control to controlling all patient access to fluids. Nursing management of water intoxication is a trial and error approach. Through a thorough assessment and close observation of the patient, the nurse can determine which interventions would be most appropriate for the patient. PMID- 1875308 TI - Battered women and the myth of masochism. AB - Domestic violence is a major health issue. Research on this problem is just in its infancy. It remains a problem because there has been widespread acceptance of violence in our culture as a means of solving and dealing with problems. Women have been the targets. Waites admonishes health professionals to stop using the concept of masochism as an explanation for abusive behavior. She asks instead for us to look at female motivation in terms of the actual choices that are available and the realistic consequences of these choices. Perhaps only then will health professionals become able to break the cycle of violence and intervene in a way that stops the woman from becoming another homicide statistic. PMID- 1875309 TI - When staff are assaulted. A nursing consultation support service. AB - Increasing patient to staff assaults led to the development of a Nursing Consultation Service, which can respond to the needs of assault victims and set the tone for institutional attitudes of nonblaming concern. A member of the consultation service meets with each known assault victim to review the incident, offer support, and provide assistance in addressing issues aroused by the incident. Implementation of this service and the use of a continuous monitor to track assault incidents is vital to highlight problem areas and develop assault prevention strategies. PMID- 1875310 TI - Dressing for success. Promoting independence among cognitively impaired elderly. AB - In demented persons, activities of daily living skills may deteriorate more quickly than their cognitive decline warrants because caregivers do not allow them to perform ADLs to the full extent of their abilities. Caregiver actions that promote independent behaviors were used with subjects in home and nursing home settings. Four of five home subjects showed decreased caregiver assistance and increased ability to dress more independently. Although nursing home subjects did not show a decrease in caregiver assistance, observation showed that some nursing home caregivers did incorporate behavioral strategies, suggesting potential clinical efficacy of the strategies. PMID- 1875311 TI - What is the impact of the use of humor as a coping strategy by nurses working in geropsychiatric settings? PMID- 1875312 TI - Helping the medicine go down. Nurses' and patients' perceptions about medication compliance. AB - The issue of medication compliance is a multidimensional phenomenon that rests not only with the patient, but also with the interactions of caregivers. Study results revealed that nurses and patients generally perceive estimated frequency of medication compliance to be similar, although increased length of time as a psychiatric nurse was associated with nurses perceiving patients as being less compliant. Reasons given by patients and nurses for medication noncompliance differed. Patients' responses were characterized by being more concrete and varied in nature than those of the nurse. PMID- 1875313 TI - Third molar surgery: the effect of primary closure, wound dressing and metronidazole on postoperative recovery. AB - One hundred and forty eight patients with bilateral symmetrically impacted lower third molars entered a clinical crossover trial to compare the effects on postoperative recovery of a Bismuth Iodoform Paraffin Paste (BIPP) socket dressing, primary closure using a resorbable suture (Softgut) and to ascertain if prophylactic metronidazole influenced the outcome. The results reaffirm the surgical principle that contaminated surgical wounds such as third molar sockets are best kept open with a dressing. Attempts at primary closure should be resisted if there is no intention to prescribe antibiotic cover. However, if a suitable antibiotic is taken then primary closure using a resorbable suture can be carried out with confidence. This may reduce the need for outpatient follow up. PMID- 1875314 TI - Historical vignette--the death of an Australian army doctor on Thursday Island in 1915 after envenomation by a stonefish. PMID- 1875315 TI - Ketamine, treatment for unwanted penile turgescence. PMID- 1875316 TI - Potential recruits in medical outpatients. PMID- 1875317 TI - Sleep manipulation prior to airborne exercises. PMID- 1875318 TI - Diabetus mellitus in the services. PMID- 1875319 TI - Smoking. PMID- 1875320 TI - Sir David Bruce Lecture 1990. "Heads and tales". PMID- 1875321 TI - Anterior cruciate ligament reconstruction using the Gore-tex ligament. AB - Twenty two Army patients with synthetic (Gore-tex) anterior cruciate ligament (ACL) reconstructions were reviewed (mean follow up 18 months). Reconstruction appeared to abolish the pivot shift sign in all cases, but some subjective instability persisted in all but 6 patients. Outcome was also assessed by medical (PULHHEEMS) grading: 6 patients were fully fit (graded L2), 7 returned to moderate activity but not full fitness (L3), and 9 remained severely incapacitated (L7 or L8) with 4 of this group being medically discharged. Specific operative complications included: prosthesis breakage (3 partial, 1 complete), infected prosthesis(1), and problems with the tibial screw(3). The range and frequency of complications was similar in other series. Physical fitness is an integral part of a soldier's job, placing particular demands on the knee and on surgical repair of knee injuries. Reports on the Gore-tex ACL prosthesis in other groups have been more encouraging, but there are difficulties in comparing this study with others. ACL insufficiency remains a serious problem, with implications for a soldier's fitness and career. The Gore-tex prosthesis improves stability but does not always allow a soldier to return to full fitness. PMID- 1875322 TI - Is patellectomy compatible with an Army career? AB - The aim of this study was to assess the impact of patellectomy on the service career of soldiers. Information on 184 individuals on whom patellectomy was performed between 1981 and 1986, was retrieved from computer records. The criterion for success of the operation was the recovery to a fully fit category. Fifty three patients (29%) regained full fitness. The outcome of patellectomies performed for chondromalacia patellae and osteoarthritis appears to be worse than that for patellar fractures. PMID- 1875323 TI - Tri-service Health Questionnaire-1989. AB - An anonymous, self administered health questionnaire survey of the habits and attitudes of servicemen in the 3 Services was conducted. The overall response rate was 75%. This paper reports the results of questions on smoking. The Army had the greatest percentage of smokers, smoked most heavily and had the worst attitude to smoking of the 3 Services. The RAF had the best results in these fields. There was a higher percentage of smoker, who smoke more heavily in Germany/seadraft than UK/shoredraft. There was a rank gradient in percentage smokers, with the lowest ranks smoking the most. A sizeable proportion of the smoking population wish to give up, have tried to do so and feel their Medical Officer should be interested in their smoking habits. A reduction in prevalence of cigarette smoking to less than 30% within 5 years is recommended as a Tri service Health Policy Goal, with the Army, Tri-Service 16-20 year olds and Private-Corporal rank equivalents and recruits, as specific target groups for intervention. The health promotion strategy should include concerted anti-smoking advice from Medical Officers. PMID- 1875324 TI - Does the ultrasound diagnosis of low-lying placenta in early pregnancy warrant a repeat scan? AB - A retrospective analysis of 732 consecutive deliveries at this hospital was undertaken to see if the early (15-20 weeks) pregnancy ultrasound placental localisation was of value, and whether the diagnosis of low-lying placenta warranted a repeat scan. The placental site was reported as normal in 413 pregnancies, as low-lying in 79 and was not recorded in 240. None of the women with a low-lying placenta developed placenta praevia. There were no significant differences in pregnancy outcome between those women with a low-lying placenta and those in whom it was normally situated. The ultrasound diagnosis of low-lying placenta between 15 and 20 weeks gestation does not warrant a repeat scan. PMID- 1875325 TI - Pilonidal sinus in an amputee. AB - A pilonidal sinus developed in the superio-medial aspect of the thigh of an above knee amputee. This is an unusual site for the condition to develop. We suggest that the same aetiological factors that were responsible for the "Jeep Bottom" of World War II were also responsible for this problem in the amputation stump of a Falklands campaign casualty. PMID- 1875326 TI - Mediastinal abscess resulting from dental infection. AB - A case of dental sepsis is presented which resulted in a deep neck infection and eventually caused a mediastinal abscess. The microbiology of such a mixed infection is briefly discussed with emphasis on the synergistic activity of the organisms. The anatomy of the fascial spaces is also described to draw attention to the possible routes of spread of this potentially life threatening condition. PMID- 1875327 TI - AJ-p97: a novel antigen of the human sperm tail fibrous sheath detected by a neurofilament monoclonal antibody. AB - Using indirect immunofluorescence (IIF), the RT97 anti-neurofilament monoclonal antibody (MoAb) detected an intracellular antigen in the principal piece of human ejaculated sperm tails. Its localisation to the tail fibrous sheath (FS) was confirmed by immunoelectron microscopy (IEM), which showed the binding of the gold particles to the outer FS surface. During spermatogenesis the antigen was first expressed on the spermatid FS, and its expression was continued on ejaculated mature sperm. In Western blotting of sperm lysates, the RT97 reacted with a 97 kDa protein (AJ-p97) which lacked disulphide bonds. This antigen was not detected on mouse or rat sperm tail FS, suggesting a sequence divergence of the AJ-p97 during evolution. The significance of these results and the relationship of AJ-p97 to neurofilaments are discussed, together with the use of the antibody as a probe for the structural dissection of the FS and for analysing the molecular events that take place during spermiogenesis, especially those involved in sperm tail morphogenesis. PMID- 1875328 TI - Human spermatozoal FA-1 binds with ZP3 of porcine zona pellucida. AB - Experiments were carried out to study the binding of the major porcine zona pellucida glycoprotein ZP3 (Mr = 55,000) with human FA-1, a fertilization-related antigen isolated from human male germ cell plasma membranes and with GA-1, a germ cell antigen isolated from murine male germ cell plasma membranes. FA-1 showed a dose-dependent binding with ZP3 in an enzyme-linked immunosorbent assay (ELISA) and by the Western blot procedure. FA-1 also bioneutralized the sperm ligand activity of ZP3 in a boar sperm/porcine zona pellucida attachment assay. In contrast, GA-1 displayed no reactivity for ZP3 using any of these procedures. These results indicate that FA-1 but not GA-1 has zona pellucida binding activity in the porcine system. PMID- 1875329 TI - Changes in natural killer cell activity in normal pregnant and postpartum women: increases in the first trimester and postpartum period and decrease in late pregnancy. AB - Changes in the activity and number of natural killer (NK) cells in peripheral blood in normal pregnant and postpartum women were examined. NK activity was measured in a 4-h 51Cr-release assay and evaluated by conventional relative lytic units and absolute lytic units which represent the total NK activity within a fixed volume of circulating blood. The number of NK cells was analyzed with FITC conjugated monoclonal antibodies and by use of an automated flow cytometer. Unexpectedly, the relative NK activity increased in the first trimester and also for 1 month postpartum compared to the activity in normal non-pregnant controls. On the other hand, absolute NK activity decreased in the third trimester compared to the activity in normal non-pregnant controls. The percentage of CD57+ cells decreased in the second trimester, but the percentage of CD16+ cells did not change during pregnancy or the postpartum period. The absolute counts of CD57+ cells and CD16+ cells decreased in the second and third trimesters and increased transiently in the postpartum period. These findings indicate that the increased NK activity in the first trimester and at 1 month postpartum is induced by increased cytotoxic activity of individual NK cells, and that the decreased NK activity in late pregnancy is induced by a decrease in the numbers of NK cells. These physiological changes may play an important role in implantation in early pregnancy, protection of the fetal allograft in late pregnancy and in the natural defense against infection during the puerperal period. PMID- 1875330 TI - Lymphocyte subsets in patients with oestrogen deficiency. AB - We have previously shown that in patients with idiopathic premature ovarian failure there were significant changes in lymphocyte subsets. To test our hypothesis that these changes were due to oestrogen deficiency we studied lymphocyte subsets in patients with oestrogen deficiency due to other causes. Blood was taken for serum oestradiol, lymphocyte counts and lymphocyte subset counts (CD2+, CD4+, CD8+ and B cells) before oestrogen replacement in 19 patients with gonadal dysgenesis, 22 patients with hypothalamic-pituitary failure and 24 healthy female control subjects. The CD4:CD8 ratio in both groups of patients was significantly lower than that in the normal control subjects while the percentages and counts of lymphocytes and CD8+ cells were significantly higher. There was a significant positive correlation between the serum oestradiol level and the CD4:CD8 ratio. These findings support the hypothesis that the changes in lymphocyte subsets are due to oestrogen deficiency. PMID- 1875331 TI - Kinetics of lymphoproliferative responses of lymphocytes harvested from the uterine draining lymph nodes during pregnancy in rats. AB - Paraaortic lymph node (PALN) cells were harvested from virgin and pregnant rats bearing syngeneic or allogeneic fetuses at all stages of pregnancy including the pre-implantation period. The specific and non-specific alloreactivity of these cells was analyzed in mixed lymphocyte reactivity (MLR) against mitomycin-C treated-paternal strain or unrelated cells. Mitogen stimulation of the cell utilized PHA, Con-A and PWM. Cells bearing T cell markers were labeled in an indirect assay using the monoclonal antibodies W3/25 and MRC OX 8. Specific alloreactivity is strongly suppressed in the pre-implantation and implantation stages of pregnancy. Specific and non-specific alloreactivities were enhanced at mid-pregnancy and normalized by the end of pregnancy. Reactivity to polyclonal mitogens is enhanced at mid-pregnancy, and the CD4+/CD8+ ratio is very low during all phases of pregnancy. PMID- 1875332 TI - HIV protease: a novel chemotherapeutic target for AIDS. PMID- 1875333 TI - Cholinergic activity of acetylenic imidazoles and related compounds. AB - A series of acetylenic imidazoles related to oxotremorine (1a) were prepared and evaluated as cholinergic agents with in vitro binding assays and in vivo pharmacological tests in mice. 1-[4-(1H-Imidazol-1-yl)-2-butynyl]-2-pyrrolidinone (1b) was a cholinergic agonist with one-half the potency of oxotremorine. Analogues of 1b with a 5- or 2-methyl substituent in the imidazole ring (compounds 1c and 1g) were cholinergic partial agonists. Analogues of 1b with a methyl substituent at the 5-position in the pyrrolidinone ring (7b) or at the alpha-position in the acetylenic chain (8b) were antagonists. Various analogues of these imidazole acetylenes where the pyrrolidinone ring was replaced by an amide, carbamate, or urea residue were prepared. Several compounds which contained 5-methylimidazole as the amine substituent were partial agonists. The activities of the imidazole compounds are compared with those of the related pyrrolidine and dimethylamine analogues. Agonist and antagonist conformations for these compounds at muscarinic receptors are proposed. PMID- 1875334 TI - Inhibitors of the protease from human immunodeficiency virus: design and modeling of a compound containing a dihydroxyethylene isostere insert with high binding affinity and effective antiviral activity. AB - The peptidomimetic template and the dihydroxyethylene isostere insert that were applied successfully to the design of renin inhibitors have been extended to the related protease from human immunodeficiency virus (HIV). The present report describes the structure-activity study leading to the identification of an inhibitor with a Ki of less than 1 nM for the HIV type-1 protease (compound II). This compound, containing a diol insert, is highly effective in blocking polyprotein processing in in vitro cell culture assays. Results obtained from kinetic analysis, studies of the stereochemistry of the insert, and modeling have led to insights as to the requisites involved in the active site-inhibitor interaction. PMID- 1875335 TI - 2-Chloro-1-(2,4-dichlorophenyl)-3-(1H-imidazol-1-yl)-2-phenylpropan-1-one hydrochloride, a novel, nonmutagenic antibacterial with specific activity against anaerobic bacteria. AB - 1-(2,4-Dichlorophenyl)-2-phenylpropen-1-one (2) is identified as a potent antibacterial agent. A compound, 2-chloro-1-(2,4-dichlorophenyl)-3-(1H-imidazol-1 yl)-2-phenylpropan++ +-1-one (5) has been designed with the intention of its acting as a pro-drug, liberating the lethal species 2 specifically within the target anaerobic bacterial cell following bioreduction by bacterial ferredoxin or related electron transfer proteins. The synthesis and biological activity of 5 is described and compared with the activities of the analogous alpha-bromo ketone 6 and alpha-fluoro ketone 7. Synthesis of 6, 7, and the corresponding alpha-hydroxy ketone 11 is also described. PMID- 1875336 TI - Synthesis and antitumor evaluations of symmetrically and unsymmetrically substituted 1,4-bis[(aminoalkyl)amino]anthracene-9,10-diones and 1,4 bis[(aminoalkyl)amino]-5,8-dihydroxyanthracene-9,10-diones. AB - The ipso bis displacements of fluoride from 1,4-difluoroanthracene-9,10-dione (3) and 1,4-difluoro-5,8-dihydroxyanthracene-9,10-dione (4) by excess of a diamine (or a monoamine) in pyridine at room temperature lead to the symmetrically substituted 1,4-bis-substituted analogues 5 and 6, respectively. The ipso monodisplacements of fluoride from 3 and 4 can be accomplished by treatment with less than 1 molar equiv of a diamine (or a monoamine) to yield 7 and 8, respectively. Treatment of 7 or 8 with a different diamine leads to the unsymmetrically substituted 1,4-bis[(aminoalkyl)amino]anthracene-9,10-diones 9 and 10, respectively. Many of the synthetic unsymmetrical analogues have been evaluated for their antitumor activity against L1210 in vitro and in vivo. Cross resistance of analogue 10a with mitoxantrone (2) and doxorubicin was evaluated against MDR lines in vitro against human colon carcinoma LOVO and its subline resistant to DOXO (LOVO/DOXO). Potential mechanisms for the observed cytotoxicity are presented and discussed. PMID- 1875337 TI - Synthesis and biological activity of angiotensin II analogues containing a Val His replacement, Val psi[CH(CONH2)NH]His. AB - The dipeptide mimic Val psi[CH(CONH2)NH]His (4) was incorporated into angiotensin II (AII) analogues to provide an octapeptide saralasin derivative (29) as well as tetrapeptide analogue 19. Three C-terminal tetrapeptides (21, 25, and 28) were also prepared. All compounds were tested for their ability to displace 3H-AII from rabbit adrenal gland homogenate and as antagonists of AII and AI on guinea pig ileum. The octapeptide analogue 29 was 700 times less active than the parent peptide 30. All the C-terminal fragments 19, 21, 25, and 28 have no measurable AII antagonist activity. Of the four tetrapeptide fragments, only 21 showed any appreciable binding activity. PMID- 1875339 TI - Synthesis and DNA-binding properties of polyamine analogues. AB - The synthesis of a series of novel polyamine analogues is reported. The DNA binding of these compounds and a variety of other polyamines were compared with their IC50 values against HeLa cell. There seemed to be no apparent correlation between the DNA binding and toxicity against HeLa cells. PMID- 1875338 TI - Conformationally restricted polysubstituted biphenyl derivatives with angiotensin II receptors antagonist properties. AB - The synthesis and in vitro activity of new nonpeptide angiotensin II antagonists is presented. Compared to previously reported biphenyl compounds, the new analogues 8 and 9 have reduced conformational freedom derived from steric hindrance. Methyl 4'-methyl-2',6'-dimethoxy[1,1'-biphenyl]-2-carboxylate 4 has been synthesized by a Von Pechmann condensation of orcinol with oxocyclohexane-2 carboxylate followed by dehydrogenation. This scheme provided the carbon skeleton of the biphenyl potentially substituted on the 2-, 2'-, 4'-, and 6'-positions. Elaboration of the subsituents led to a biphenyl derivative used to alkylate a 2 n-butyl-4-chloro-5-(hydroxymethyl)imidazole. After coupling with the imidazole two regioisomers were separated and identified by 1H NMR. NOESY experiments were useful to establish regiochemistry of the final products that have angiotensin II blocking activity. Their affinity for angiotensin II receptors was established in a binding assay experiment and in an isolated organ test. The presence of 2',6' dimethoxy substituent on the biphenyl moiety of the antagonist was found to significantly decrease affinity for the receptor. PMID- 1875340 TI - Synthesis of structural analogues of lyngbyatoxin A and their evaluation as activators of protein kinase C. AB - Syntheses of several new analogues of lyngbyatoxin A from a single common intermediate are described. These compounds bear a carbon chain at the 7-position of the indolactam V (ILV) nucleus which contains either a hydrophilic or a lipophilic group. The effect of these minor structural alterations on the ability of the ILV analogues to activate the enzyme protein kinase C (PKC) was determined by measuring the extent of phosphorylation of calf thymus histone (III-S). Introduction of a hydroxyl group on the C-7 appendage was found to dramatically decrease compound 3's ability to activate PKC. This result is interpreted in terms of the decreased ability of 3 to associate with the membrane bilayer. PMID- 1875341 TI - Preparation and anticonvulsant activity of a series of functionalized alpha heteroatom-substituted amino acids. AB - Potent anticonvulsant activity has been reported for (R,S)-2-acetamido-N-benzyl-2 methylacetamide (2a). Select alpha-heteroatom substituted derivatives of 2a have been prepared (26 examples) in which the alpha-methyl group has been replaced by nitrogen (3a-q), oxygen (3r-u), and sulfur (3v-z) containing moieties. The functionalized amino acid derivatives were evaluated in the maximal electroshock seizure (MES) and horizontal screen (tox) tests in mice. The most active compounds were (R,S)-2-acetamido-N-benzyl-2-(methoxyamino)acetamide (31), and (R,S)-2-acetamido-N-benzyl-2-(methoxymethylamino)acetamide (3n). After ip administration, the MES ED50 values for 31 (6.2 mg/kg) and 3n (6.7 mg/kg) compared favorably with phenytoin (9.50 mg/kg). PMID- 1875342 TI - Aldosterone antagonists. 4. Synthesis and activities of steroidal 6,6-ethylene 15,16-methylene 17-spirolactones. AB - Several steroidal 6,6-ethylene-15,16-methylene 17-spirolactones were synthesized to find new progestogens that exhibit both progestational and antimineralocorticoidal activities. The influence of substituents in the 10- and 13-position of the steroidal framework on both properties was investigated. It was found that only compound 12, carrying methyl groups at the 10- and 13 positions, possesses high progestational and antimineralocorticoidal activity. PMID- 1875343 TI - Synthesis and evaluation of antiinflammatory activities of a series of corticosteroid 17 alpha-esters containing a functional group. AB - A series of 21-desoxy-21-chlorocorticosteroids that contain a functionalized ester group at 17 alpha has been prepared and examined to separate their systemic activity from topical antiinflammatory activity. Introduction of the functionalized ester group at 17 alpha was carried out by an acid-catalyzed formation of cyclic ortho esters with 17 alpha,21-hydroxyl groups of corticosteroids and subsequent acid-catalyzed hydrolysis. As for the functional group, chloro, methoxy, acetoxy, cyano, cyclopropyl, or alkoxycarbonyl group was introduced at the terminal carbon atom of the 17 alpha-alkanoate group. The topical antiinflammatory activity and systemic activity of these compounds were examined and found to be significantly dependent on the functionalities in the 17 alpha-esters. Among these derivatives, a series of 17 alpha (alkoxycarbonyl)alkanoates (17 alpha-OCO(CH2)nCOOR) showed an excellent separation of the systemic activity from topical activity. The effects of the number of methylene groups (n) and of the alkyl groups of the ester (R) on either topical or systemic activity of the corticosteroid derivatives were also investigated. PMID- 1875344 TI - 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 8. Side chain ether analogues of lovastatin. AB - A general route for preparing side chain ether analogues of lovastatin is presented. These analogues proved to be weaker inhibitors of HMG-CoA reductase than the corresponding side chain ester analogues. Interestingly, inhibitory potency was enhanced markedly when the 4-fluoro group was incorporated in the aromatic moiety of the side chain benzyl group of 2d. PMID- 1875345 TI - A new class of analogues of the bifunctional radiosensitizer alpha-(1 aziridinylmethyl)-2-nitro-1H-imidazole-1-ethanol (RSU 1069): the cycloalkylaziridines. AB - A series of compounds related to alpha-(1-aziridinylmethyl)-2-nitro-1H-imidazole 1-ethanol (RSU 1069, 1) were synthesized and evaluated as selective hypoxic cell cytotoxic agents and as radiosensitizers. The aziridine moiety was replaced with a number of other potential alkylating groups including cycloalkylaziridines and azetidines. The data indicated that modification of the aziridine of 1 resulted in a substantial decrease in the ability of the compounds to selectively kill hypoxic cells. However, these modifications did not affect the compounds' in vitro radiosensitizing activity since many of the derivatives were as potent as 1. All of the compounds that were evaluated in vivo were less toxic than 1, and several members of this series had significant activity. The best compound was trans-alpha-[[(4-bromotetrahydro-2H-pyran-3-yl) amino]methyl]-2-nitro-1H imidazole-1-ethanol (18), which, due to its activity and log P value, is a candidate for additional in vivo studies. PMID- 1875346 TI - 3-Hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors. 7. Modification of the hexahydronaphthalene moiety of simvastatin: 5-oxygenated and 5-oxa derivatives. AB - Modification of the hexahydronaphthalene ring 5-position in simvastatin 2a via oxygenation and oxa replacement afforded two series of derivatives which were evaluated in vitro for inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and acutely in vivo for oral effectiveness as inhibitors of cholesterogenesis in the rat. Of the compounds selected for further biological evaluation, the 6 beta-methyl-5-oxa 10 and 5 alpha-hydroxy 16 derivatives of 3,4,4a,5-tetrahydro 2a, as well as, the 6 beta-epimer 14 of 16 proved orally active as hypocholesterolemic agents in cholestyramine-primed dogs. Subsequent acute oral metabolism studies in dogs demonstrated that compounds 14 and 16 evoke lower peak plasma drug activity and area-under-the-curve values than does compound 10 and led to the selection of 14 and 16 for toxicological evaluation. PMID- 1875347 TI - Synthesis and biochemical studies of 16- or 19-substituted androst-4-enes as aromatase inhibitors. AB - Androst-4-en-17-one derivatives [19-acetoxide 4, 16-bromides 14 and 15, 19,19 difluoride 18, and (19R,S)-19-acetylenic alcohol 25] and androst-4-en-17 beta-ol derivatives 3, 5, 10, 12, and 19 were synthesized and tested for their ability to inhibit aromatase in human placental microsomes. All the 17-oxo steroids, except compound 25 and 17,19-diol 3 of this series, were effective competitive inhibitors with apparent Ki's ranging from 170 to 455 nM. 19,19-Difluoro steroid 18 and 19-acetylenic alcohol 25, a weak competitive inhibitor (Ki = 7.75 microM), caused a time-dependent, pseudo-first-order inactivation of aromatase activity with kinact's of 0.0213 and 0.1053 min-1 for compounds 18 and 25, respectively. NADPH and oxygen were required for the time-dependent inactivation, and the substrate, androst-4-ene-3,17-dione, prevented it, but a nucleophile, L-cysteine, did not in each case. The results strongly suggest that aromatase would attack the 19-carbon of steroids 18 and 25. PMID- 1875348 TI - Nonpeptide angiotensin II receptor antagonists: the discovery of a series of N (biphenylylmethyl)imidazoles as potent, orally active antihypertensives. AB - A new series of nonpeptide angiotensin II (AII) receptor antagonists has been prepared. These N-(biphenylyl-methyl)imidazoles, e.g. 2-butyl-1-[(2' carboxybiphenyl-4-yl)methyl]-4-chloro-5- (hydroxymethyl)imidazole, differ from the previously reported N-(benzamidobenzyl)imidazoles and related compounds in that they produce a potent antihypertensive effect upon oral administration; the earlier series generally were active only when administered intravenously. It has been found that the acidic group at the 2'-position of the biphenyl is essential. Only ortho-substituted acids possess both high affinity for the AII receptor and good oral antihypertensive potency. The carboxylic acid group has been replaced with a variety of acidic isosteres, and the tetrazole ring has been found to be the most effective. The tetrazole derivative, DuP 753, is currently in development for the treatment of hypertension. PMID- 1875349 TI - Highly selective adenosine A2 receptor agonists in a series of N-alkylated 2 aminoadenosines. AB - A wide variety of 2-substituted aminoadenosines were prepared for comparison with the moderately A2 receptor selective adenosine agonist 2-anilinoadenosine (CV 1808). High selectivity combined with significant affinity at the A2 receptor in rat membranes was observed for those amines bearing a two-carbon chain to which was attached an aryl, heteroaryl, or alicyclic moiety. 2-(2 Phenethylamino)adenosine (3d), a 14-fold A2 selective compound, was modified by introduction of a variety of substituents in the benzene ring and the side chain. Some of these changes led to improved A2 affinity and increased selectivity. Replacement of the phenyl moiety by cyclohexenyl produced a 210-fold selective agonist 3ag (CGS 22989) whereas the cyclohexanyl analogue 3af (CGS 22492) was 530 fold selective at the A2 site. These compounds showed hypotensive activity in rat models over a range of doses without the bradycardia observed with less selective agonists. PMID- 1875350 TI - Synthesis and evaluation of stilbene and dihydrostilbene derivatives as potential anticancer agents that inhibit tubulin polymerization. AB - An array of cis-, trans-, and dihydrostilbenes and some N-arylbenzylamines were synthesized and evaluated for their cytotoxicity in the five cancer cell cultures A-549 lung carcinoma, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma, SKMEL-5 melanoma, and MLM melanoma. Several cis-stilbenes, structurally similar to combretastatins, were highly cytotoxic in all five cell lines and these were also found to be active as inhibitors of tubulin polymerization. The most active compounds also inhibited the binding of colchicine to tubulin. The most potent of the new compounds, both as a tubulin polymerization inhibitor and as a cytotoxic agent, was (Z)-1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene (5a). This substance was almost as potent as combretastatin A-4 (1a), the most active of the combretastatins, as a tubulin polymerization inhibitor. Compound 5a was found to be approximately 140 times more cytotoxic against HT-29 colon adenocarcinoma cells and about 10 times more cytotoxic against MCF-7 breast carcinoma cells than combretastatin A-4. However, 5a was found to be about 20 times less cytotoxic against A-549 lung carcinoma cells, 30 times less cytotoxic against SKMEL-5 melanoma cells, and 7 times less cytotoxic against MLM melanoma cells than combretastatin A-4. The relative potencies 5a greater than 8a greater than 6a for the cis, dihydro, and trans compounds, respectively, as inhibitors of tubulin polymerization are in agreement with the relative potencies previously observed for combretastatin A-4 (1a), dihydrocombretastatin A-4 (1c), and trans combretastatin A-4 (1b). The relative potencies 5a greater than 8a greater than 6a were also reflected in the results of the cytotoxicity assays. Structure activity relationships of this group of compounds are also discussed. PMID- 1875351 TI - Relaxant activity of 6-cyano-2,2-dimethyl-2H-1-benzopyran-4-carboxamides and thiocarboxamides and their analogues in guinea pig trachealis. AB - Structural modifications of the potassium channel activator cromakalim (1) are described in which the amide moiety at C-4 has been replaced by carboxamide and thiocarboxamide functions. Analogues in which the hydroxyl group at C-3 has been oxidized or removed are also disclosed. Such analogues display an interesting profile of smooth muscle relaxant activity in the guinea pig isolated trachea, not all of which appears to result from the opening of potassium channels, but few compounds retain useful in vivo activity. However, one compound in particular, 6-cyano-2,2-dimethyl-N-methyl-2H-1-benzopyran-4-thiocarboxamide (13) was shown to be a potent potassium channel activator in vitro and to provide prolonged protection to guinea pigs from the respiratory effects of inhaled histamine. PMID- 1875352 TI - Synthesis, stereochemistry, and biological activity of the 1-(1-phenyl-2 methylcyclohexyl)piperidines and the 1-(1-phenyl-4-methylcyclohexyl)piperidines. Absolute configuration of the potent trans-(-)-1-(1-phenyl-2 methylcyclohexyl)piperidine. AB - The (-)- and (+)-isomers of the cis- and trans-Ph/Me 1-(1-phenyl-2 methylcyclohexyl)piperidines have been synthesized and the achiral cis- and trans Ph/Me 1-(1-phenyl-4-methylcyclohexyl)piperidines were prepared, and their in vitro [displacement of [3H]TCP (1-[1-(2-thienylcyclohexyl)]piperidine) from the PCP (1-(1-phenylcyclohexyl)piperidine) binding site] and in vivo (rotarod assay) activities determined. The 1-(1-phenyl-2-methylcyclohexyl)piperidine isomers were resolved by classical crystallization procedures, through the diastereomeric salts obtained with d- and l-10-camphorsulfonic acid. The relative stereochemistry of the cis- and trans-Ph/Me 1-(1-phenyl-2 methylcyclohexyl)piperidines and the achiral cis- and trans-Ph/Me 1-(1-phenyl-4 methylcyclohexyl)piperidines was established by using 13C and 1H NMR. Both (-) trans-1-(1-phenyl-2-methylcyclohexyl)piperidine ((-)-2) and (+)-trans-1-(1-phenyl 2-methylcyclohexyl)piperidine ((+)-2) were examined by single-crystal X-ray analysis, and the absolute configuration of (-)-2 was determined to be 1S,2R. The (-)-2 was found to be about five times more potent than PCP in vitro and twice as potent in vivo. It is the most potent of all of the simple methyl-substituted cyclohexyl PCP isomers and is among the most potent PCP-like compounds which have been synthesized. It was nine times more potent in vitro and four times more potent in vivo than (+)-2. The racemic cis-1-(1-phenyl-2 methylcyclohexyl)piperidine (3), and its enantiomers ((+)-3 and (-)-3), were essentially inactive in vitro and in vivo. The cis-Ph/Me 1-(1-phenyl-4 methylcyclohexyl)piperidine (18) was more potent than trans-Ph/Me 1-(1-phenyl-4 methylcyclohexyl)piperidine (17), but considerably less potent than (-)-2. The enantioselectivity observed at the PCP binding site for (-)-2 could indicate that this site can discriminate between enantiotopic edges of the achiral PCP (choosing the pro-1-S edge), as does the mu-opioid receptor in the prodine series of opioids. Benzimidoyl or benzoyl group replacement of the phenyl ring in the 1 (1-phenyl-2-methylcyclohexyl)piperidine series gave compounds which showed little in vitro and in vivo activity. PMID- 1875353 TI - Acyclic analogues of 2-(4-phenylpiperidino)cyclohexanol (vesamicol): conformationally mobile inhibitors of vesicular acetylcholine transport. AB - Several 1,3-disubstituted propan-2-ols and one alpha,beta-disubstituted ethanol (11i) were synthesized and evaluated as potential acyclic mimics of the vesicular acetylcholine transport inhibitor 2-(4-phenylpiperidinyl)cyclohexanol (1, vesamicol, AH5183). Analogues containing the 4-phenylpiperidyl fragment (11a, 11b) were more potent than those containing the 4-phenylpiperazyl moiety (11e, 11f). Substitution at the second terminal carbon of the propyl (or ethyl) fragment with simple lipophilic aryl substituents yielded potent inhibitors of vesicular acetylcholine storage, including (-)-11a and d-11i, which are equipotent with vesamicol. However, the activity of analogues containing bicyclic aryl groups was susceptible to aryl substitution patterns (11g vs 11h), indicating a definite receptor site topography. In addition, the inhibitory activity of these acyclic analogues was enantioselective, exhibiting a preference, similar to the parent vesamicol, for the levorotatory isomer [(-)-11a vs (+)-11a]. Therefore, the simple lipophilic acyclic vicinal amino alcohols may successfully mimic the biological activity of vesamicol. PMID- 1875354 TI - Synthesis of 2-deoxy-2-[(2,2-difluoro-3-hydroxytetradecanoyl)amino]-3-O- [(R)-3 (tetradecanoyloxy)tetradecanoyl]-D-glucopyranose 4-phosphate. AB - 2-Deoxy-2-[(2,2-difluoro-3-hydroxytetradecanoyl)amino]-3-O-[(R)-3- (tetradecanoyloxy)tetradecanoyl]-D-glucopyranose 4-phosphates (9H,L) were synthesized from allyl 2-amino-2-deoxy-4,6-O- isopropylidene-beta-D glucopyranoside (1), (+/-)-3-[(benzyloxycarbonyl)oxy]-2,2-difluorotetradecanoic acid, and (R)-3- (tetradecanoyloxy)tetradecanoic acid. Both compounds 9H and 9L were more active than GLA-60 for the prostaglandin D2 releasing test on macrophages. PMID- 1875355 TI - 3-(5-Alkyl-4-hydroxy-3-methoxy-1-naphthalenyl)-2-methyl-2-propenoic acids as orally active inhibitors of IL-1 generation. PMID- 1875356 TI - The evolutionary relationships among arboviruses and the evolutionary relationships of their vectors provides a method for understanding vector-host interactions. PMID- 1875357 TI - Wood rats and kangaroo rats: potential reservoirs of the Lyme disease spirochete in California. AB - The etiologic agent of Lyme disease, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, was isolated repeatedly from dusky-footed wood rats, Neotoma fuscipes Baird, and California kangaroo rats, Dipodomys californicus Merriam, in northern California. All animals were collected in a region endemic for Lyme disease but for which the natural reservoir of B. burgdorferi was unknown. Similar attempts to isolate spirochetes from lizards, other species of rodents, jack rabbits, and deer between 1987 and 1991 were unsuccessful. Spirochetes isolated from wood rats and kangaroo rats were antigenically similar to strains of B. burgdorferi that had been isolated previously from the western black-legged tick, Ixodes pacificus Cooley & Kohls, in California. Similar enzootic cycles involving wood rats or kangaroo rats should be sought in other regions of the United States where the reservoirs of this spirochete are unknown. PMID- 1875358 TI - Insect repellent N,N-diethylphenylacetamide: an update. AB - N,N-diethylphenylacetamide (DEPA) has repellent activity against hematophagous insects including mosquitoes, black flies, horse flies, muscoid flies, rat fleas, and ticks, as well as land leeches and cockroaches. The efficacy of DEPA is comparable to that of N,N-diethyl-3-methylbenzamide (DEET) in both laboratory and field tests. Toxicological studies indicate that DEPA is safe for human use. Different formulations as well as fabrics impregnated with DEPA are effective for personal protection from insect bites. PMID- 1875359 TI - Species composition of the Anopheles gambiae complex (diptera: Culicidae) at two sites in western Kenya. AB - At two sites in the Kisumu area of western Kenya, the species composition of the Anopheles gambiae complex was determined by analysis of ovarian polytene chromosomes. Of 1,915 females, 26.1% were An. arabiensis Patton and 73.9% were An. gambiae Giles; one arabiensis x gambiae hybrid was identified. No major differences in the proportions of An. arabiensis and An. gambiae were observed between sites or between years. The ratio of An. arabiensis/An. gambiae was 6.7:1 (n = 231) in cow-baited traps, 0.2:1 (n = 1,525) in indoor resting samples, and 0.5:1 (n = 145) in all-night human bait catches. The proportion of An. arabiensis decreased progressively from 50.0% to 8.3% (n = 1,129) during 11 wk from September to November 1987; this change was correlated negatively with night temperature and positively with temperature range. In cow-baited traps, 97.4% (n = 194) of An. arabiensis were cow-fed and 95.8% (n = 1,054) of An. gambiae from indoor resting collections were human-fed. In indoor collections, 37.2% (n = 215) of An. arabiensis were cow-fed and 23.1% (n = 26) of An. gambiae from cow traps were human-fed. This demonstrates post-blood-feeding endophily by An. arabiensis and suggests post-blood-feeding exophily by An. gambiae. Malaria infection rates were higher for An. gambiae than for An. arabiensis by a ratio of 3:1 in 1986 (by Plasmodium falciparum ELISA) and 2.3:1 in 1987 (by dissection). Despite the higher proportion of infective An. gambiae, both species in this area serve as efficient vectors through their remarkably stable contact with the human population as demonstrated by their blood feeding and resting behavior. PMID- 1875360 TI - Stimulation of vitellogenesis by pyrethroids in mated and virgin female adults, male adults, and fourth instar females of Ornithodoros moubata (Acari: Argasidae). AB - The effects of several pyrethroids on vitellogenesis, i.e., vitellogenin (Vg) synthesis and ovarian development in unfed mated female adults of Ornithodoros moubata were investigated. Survival of ticks treated with pyrethrin, resmethrin, and etophenprox was very low. Ticks treated with cypermethrin (CyM), fenvalerate (Fev), and flucythrinate (Flu) survived even when high concentrations were used. Vg titer in the hemolymph of unfed mated females was the same level on day 5 and about three times higher on day 10 after treatment with CyM, Fev, and Flu, as that of engorged adult females. CyM was the most effective in inducing vitellogenesis and was further evaluated in unfed virgin females, males, and fourth instars. CyM was shown to stimulate vitellogenesis in unfed virgin females adults. Oviposition did not occur but ovaries were well developed. CyM also was shown to stimulate Vg in the hemolymph of unfed and fed adult males; however, the Vg levels were very low compared to that of engorged adult females. Extremely high concentrations of Vg were observed in the hemolymph of female nymphs (fourth instar), particularly engorged nymphs, treated with CyM (10 micrograms). No ovarian development was observed in these nymphs. Vg stimulated by CyM was shown to be immunologically and electrophoretically the same as that of normal engorged females. PMID- 1875361 TI - Distribution of sandflies (Diptera: Psychodidae) in three vegetation habitats in the Marigat area, Baringo District, Kenya. AB - A total of 4,467 phlebotomine sandflies representing nine species and two genera were collected using polythene material coated with castor oil in three vegetation types in Marigat area from February to May 1986. Sandfly relative abundance was greatest in the closed-canopy forest (61% of total catch), followed by the open-canopy woodland (38%) and the thicket (1%). Nine species of sandflies were collected in both the closed-canopy forest and the open-canopy woodland. The thicket yielded only four species. The sandfly population in the vegetation was composed of Sergentomyia bedfordi (61%), S. antennatus (31%), S. ingrami (3%), S. schwetzi (2%), and S. africanus (1%). Plebotomus species rarely occurred in the study area. In the closed-canopy forest and the open-canopy woodland, female S. bedfordi were most abundant during the dry season, while males predominated during the wet period. Inversely, more male S. antennatus were collected during the dry season, while females predominated in the open-canopy woodland during the wet season. In the closed-canopy forest, male S. antennatus outnumbered the females during both dry and wet seasons. Both S. antennatus and S. bedfordi increased in abundance during the dry season. PMID- 1875362 TI - Mark-release-recapture studies with Culex mosquitoes (Diptera: Culicidae) in Southern California. AB - Cohorts of Culex adults were marked uniquely with date- and site-specific fluorescent dust colors and were released at centrally located residences and at peripheral breeding sources to study population dispersal, size, additions, and deletions. The recapture rate of Cx. quinquefasciatus females was higher and the mean distance dispersed was lower in residential than in agricultural or park habitats. Dispersal was associated with host-seeking activity and ranged from 0.6 to 1.0 km/d. Survivorship ranged from 0.65 to 0.84 per day, and population density ranged from 36,612 to 671,634 females per km2. The sampling efficiency of CO2-baited traps in residential habitats increased coincidentally with increasing population density. Gravid traps were most effective in residential habitats where there were few competitive oviposition sites. Teneral Cx. stigmatosoma were extremely dispersive, and few marked females were recaptured. Unmarked females were more abundant at CO2-baited traps in residential habitats than at traps near productive peripheral breeding sources. Few Cx. tarsalis were released, and the recapture rate in residential habitats was low when compared with rural sites. PMID- 1875363 TI - Time-activity budget of adult screwworm behavior (Diptera: Calliphoridae). AB - A time-activity budget of adult screwworm behavior was determined in an outdoor screened enclosure. Screwworms spent most (75.7%) of their time in the passive behaviors of resting and grooming. The adults spent 9.5% of daytime activity feeding, mainly on flowers or nectaries, but also on animal wound fluids and feces. Adults moving in vegetation preferred walking over flying in both frequency and duration. Flying was a frequent activity, but flights were of short (13.7 s) duration. Courtship, mating, and oviposition constituted less than 1% of a fly's total activity. The unusual behavior characterized as "bubbling" was interpreted as either thermoregulation or a nectar concentration. PMID- 1875364 TI - Aedes triseriatus (Diptera: Culicidae) and La Crosse virus. IV. Nutritional deprivation of larvae affects the adult barriers to infection and transmission. AB - Groups of Aedes triseriatus (Say) were reared either as nutritionally deprived (two regimens) or well fed (one regimen) throughout larval development, and the vector competence of resulting small, normal, and large females was assessed for La Crosse virus. When fed a high dose of virus (4.6 log10/0.025 ml in Vero cell culture), 90% of small Ae. triseriatus females transmitted La Crosse virus to suckling mice compared with 70% of normal and 42% of large females. Among small females, 100% had disseminated infections as did 86% of normal females, whereas only 69% of large females had disseminated infections. All females had infected mesenterons (midguts). When fed a low dose of virus (2.2 log10/0.025 ml in Vero cell culture) in a second experiment, 15% of small females transmitted compared with 0% of large females; 50% of small females developed disseminated infections compared with 16% of large females. mesenteronal infection occurred in 70% of small but only 32% of large females. Electron microscopy of mesenteronal tissues from large and small females revealed physical differences in the basement membranes (basal laminae). The mesenterons of small females had 3-6 laminae (mean thickness of the basement membrane = 0.14 microns) compared with 9-16 laminae (mean thickness of the basement membrane = 0.24 microns) in large females. These morphological differences indicated that the mesenteronal escape barrier, which accounted for the difference in the percentage of small and large females with disseminated infections, may be, in part, a physical barrier that was modified by nutritional deprivation in the larval instars. PMID- 1875365 TI - Blood consumption by the cat flea, Ctenocephalides felis (Siphonaptera: Pulicidae). AB - The volume of blood consumed by actively reproducing female cat fleas, Ctenocephalides felis (Bouche), while feeding in confinement feeding chambers on cats for 3 h, was investigated using two radionuclide blood tags (51Cr erythrocyte and 125I-albumin) and the gravimetric method. Female fleas consumed an average of 0.110 ml (+/- 0.026 ml) of blood per 100 females in 3 h as determined using the dual radionuclide system. The single 51Cr-erythrocyte tag overestimated blood consumption by 11.3% and the single 125I-albumin tag underestimated blood consumption by 6.4%. The gravimetric method underestimated blood consumption by 72.2% compared with the dual radionuclide value. Investigations of blood consumption of nonconfined female fleas were conducted with cats housed in metabolic cages and restricted from grooming. These investigations were conducted using the single 51Cr-erythrocyte tag, and the data obtained were corrected to compensate for using a single erythrocyte tag. Female cat fleas consumed an average of 13.6 microliters (+/- 2.7 microliters) of blood per day, which was equivalent to 15.15 times their body weight. In an additional study, direct exposure to 40 kHz ultrasound did not reduce blood consumption by the fleas. PMID- 1875366 TI - Two new species of chiggers (Acari: Trombiculidae) from small mammals collected in Brazil. AB - Two new species of chiggers are described from mammals collected in Fazenda Agua Limpa, Federal District, Brazil: Trombewingia brasiliensis from Bolomys lasiurus and Parasecia lasiurus from B. lasiurus and Oxymycterus sp. PMID- 1875367 TI - Venezuelan equine encephalomyelitis virus infection in and transmission by the tick Amblyomma cajennense (Arachnida: Ixodidae). AB - To assess a possible role of ticks as the maintenance host for epizootic strains of Venezuelan equine encephalomyelitis (VEE) virus, laboratory experiments were conducted to determine if ticks could become infected, maintain, and transmit the virus. Larval and nymphal Amblyomma cajennense (F.) and larval Dermacentor nitens Neumann ticks were exposed to epizootic VEE virus (Trinidad donkey strain) by allowing them to feed on viremic guinea pigs (strain 13). In A. cajennense, transstadial transmission was observed from larvae to nymphs and adults. Horizontal viral transmission to a mammalian host was accomplished by nymphs. Infection rates in nymphs and adults were 2% (42/2,750) and 4% (9/244), respectively, afer ingestion of virus as larvae. Virus was detected in A. cajennense adult ticks for up to 171 d after infection in the larval stage. A cajennense, exposed as nymphs, ingested virus but did not become infected (0/164 after 10 d after taking an infective bloodmeal). No virus was detected in D. nitens 7 d after exposure. These findings suggest that A. cajennense potentially could be involved in an interepizootic maintenance cycle of epizootic VEE viral strains. PMID- 1875368 TI - Defensive behavior of eastern chipmunks against Aedes triseriatus (Diptera: Culicidae). AB - Eastern chipmunks (Tamias striatus L.) were placed in Plexiglas cages with 0, 2, 5, 10, or 20 female Aedes triseriatus Say mosquitoes for 2 h. Previously published studies demonstrated little effective mosquito defensive behavior because of pause behavior by the chipmunks. By recording chipmunk behavior on videotape, pause behavior was reduced, and the chipmunks exhibited effective mosquito defense. The chipmunks defended themselves actively by attacking mosquitoes in flight, biting, head shaking, body turning, face grooming, hindfoot scratching, and flicking the tail. These defensive behaviors were correlated positively with the number of mosquitoes exposed to the chipmunks and with the number of mosquitoes killed. PMID- 1875369 TI - Comparative sensitivity of four Anopheles (Diptera: Culicidae) to five repellents. AB - Five repellents were evaluated against Anopheles albimanus Wiedemann An. freeborni Aitken, An. gambiae Giles, and An. stephensi Liston, using a "free choice," dose-response testing procedure on rabbits. Overall, deet was the most effective repellent based on effective dosages (ED50's and ED95's), except against An. albimanus. An. albimanus was significantly more tolerant to deet compared with dimethyl phthalate or ethyl hexanediol. Permethrin was effective against all four anopheline species at the ED50 levels; however, the ED95 values were higher compared with the other repellents. There were significant differences in sensitivity of some of the four species to all the repellents tested, except dimethyl phthalate and indalone. The variability in the response of these anopheline species to repellents confirm that the extrapolation of repellent data from one anopheline species to another is unreliable and that comprehensive tests are needed for each species. PMID- 1875370 TI - Mermithid (Nematoda: Mermithidae) parasitism of Simulium damnosum s.l. (Diptera: Simuliidae) in Sierra Leone and the need for vector control. AB - Females of Simulium damnosum Theobald s.l. were systematically collected at four sites in the Gorawa Chiefdom of Sierra Leone, West Africa, over a period of 15 mo from July 1986 to September 1987. The prevalence of mermithids infecting parous females varied from 0 to 7.9%, whereas the prevalence of mermithids in nulliparous females varied from 0 to 42.8%. The peak incidences of mermithid infection in nulliparous females occurred during the rainy season (15.2% in October 1986, 42.8% in August 1987). The high incidence of mermithids was associated with a high monthly biting rate, particularly during the month before the peak mermithid period (5,240 in September 1986, 4,878 in July 1987). PMID- 1875371 TI - Effect of an experimental systemic compound, CGA-184699, on life stages of the cat flea (Siphonaptera: Pulicidae). AB - The experimental drug CGA-184699 (N-[2,5-dichloro-4-(1,1,2,3,3,3 hexafluoropropoxy)-phenylaminoc arbonyl]-2,6-difluorobenzamide) was evaluated for efficacy against cat fleas, Ctenocephalides felis (Bouche), held in flea cages on cats. When administered orally, the compound acts systemically and prevents development of the next generation of fleas. There was no effect on adults, but eggs from adults that fed on treated cats had reduced viability. Most larvae that emerged from surviving eggs died. Within the first 2 wk after treatment of cats with CGA-184699, most death of progeny occurred in the egg stage, but as time passed, more eggs hatched but larval mortality prevented development to adults. A single oral dose of CGA-184699 virtually eliminated the next generation of adult fleas for a period of 44 d. PMID- 1875372 TI - Distribution of biting Culex tritaeniorhynchus (Diptera: Culicidae) among pigs: effects of host size and behavior. AB - The distribution of biting Culex tritaeniorhynchus Giles females among pigs was analyzed to determine the effect of host size and behavior on host selection by the mosquitoes. The number of Cx. tritaeniorhynchus collected per sow was significantly greater than that on her piglets. Sleeping piglets were attacked more frequently by mosquitoes than wakeful ones. The distribution of biting mosquitoes among different-sized piglets was aggregated compared with expected random distribution, and one of four data sets showed significant host size dependence. Pig activity (including mosquito defensive behavior) significantly reduced the number of attacking mosquitoes, but total pig activity score was not related significantly to total mosquito counts during the early half of the night or the entire night. Data on the residence times of mosquitoes on pigs indicated that interrupted (and consequently multiple feedings) were frequent. The effects of size-dependent (age-dependent) host selection by Cx. tritaeniorhynchus on the amplification of Japanese encephalitis virus were discussed in relation to control programs. PMID- 1875373 TI - Glauconyssus: a new genus associated with African bats (Acari: Macronyssidae). AB - Glauconyssus, n. g., is elected for Glauconyssus tanzaniensis, n. sp., a parasitic mite of Glauconycteris poensis from Mt. Kilimanjaro, Tanzania. PMID- 1875374 TI - Artificial feeding of Ornithodoros concanensis (Acari: Argasidae) nymphs on bovine blood and morphological changes in erythrocytes undergoing hemolysis in the tick midgut. AB - The morphology of bovine erythrocytes undergoing hemolysis in the midgut of the argasid tick Ornithodoros concanensis Cooley & Kohls was examined after feeding nymphal ticks artificially on parafilm and latex membranes. Percentage of successful feeding was significantly higher on parafilm (63%) than on latex (43%) membrane. However, there was no difference in the amount of blood taken per tick. Scanning electron microscopy was used to follow the morphological changes of red blood cells in the tick gut during an 80-h postfeeding period. Erythrocytes converted from normal discocytes to spiculated cells (echinocyte stage III) within 20 h. During the development of spicules (echinocytosis), erythrocytes lost membrane surface area by the release of microvesicles. At 30 h after feeding, the first spherocytes appeared and after 80 h, only smooth spheres of different sizes were present. Reasons for the observed modifications in red blood cell morphology are discussed. PMID- 1875375 TI - Ectoparasites of a population of urban gray squirrels in northern Florida. AB - Ectoparasites infesting a population of urban gray squirrels (Sciurus carolinensis Gmelin) in northern Florida were collected monthly during 1974. Eleven species were identified: one flea (Orchopeas howardi (Baker], three suckling lice (Enderleinellus longiceps Kellogg & Ferris, Hoplopleura sciuricola Ferris, and Neohaematopinus sciuri Jancke), one tick (Dermacentor variabilis Say), two mesostigmatid (gamasid) mites (Androlaelaps casalis (Berlese) and A. fahrenholzi (Berlese], and four chiggers (Eutrombicula alfreddugesi (Oudemans), E. splendens (Ewing), Leptotrombidium peromysci Vercammen-Grandjean & Langston, and Parasecia gurneyi (Ewing]. The flea and three suckling lice represent core species of ectoparasites for the gray squirrel; the remainder are probably satellite species. Only E. longiceps varied significantly in prevalence or intensity of infestation among host age groups; subadult squirrels had higher intensities than adults. Peak prevalence of O. howardi occurred in January and attained maximum intensity in March, whereas both prevalance and intensity were minimum in August. Prevalence of H. sciuricola was maximum in November and remained at similar levels through June. It then declined significantly to its minimum in September-October. Intensity of infestation, however, was greatest in August, September, and January. Maximum prevalence of N. sciuri occurred from January to March and was minimum in September; intensity of infestation reached maxima in January, June, and August. PMID- 1875376 TI - Effect of ivermectin on the volume of blood ingested by two species of ticks (Acari: Ixodidae) feeding on cattle. AB - Females of the lone star tick, Amblyomma americanum (L.), and the American dog tick, Dermacentor variabilis (Say), were fed on ivermectin (Ivomec)-treated and untreated bovines to determine the effect of the acaricide on volume of blood ingested and to compare the weight differences between the treatment and control groups at various time intervals after attachment. Adult females from each genus were collected from Bos tarus hosts and subjected to hematin assays on three collection dates to estimate the volume of blood ingested. Before feeding, lone star ticks contained an average of 2.0 microliters of blood and had an average weight of 5.2 mg. Unengorged American dog tick females had an average blood volume of 3.3 microliters and a mean weight of 5.8 mg. Ticks of both species reacted to ivermectin by expressing lower mean weights, and they consumed smaller quantities of blood. Lone star tick females were significantly affected in terms of amount of blood consumed and body weight changes when compared with control ticks. After feeding on treated cattle, lone star tick females contained smaller quantities of blood than pretreatment females, but there were no significant differences observed until day 12 between the control and the treated groups. American dog tick females on treated hosts had measurable quantities of blood that were significantly different among the experimental groups. PMID- 1875377 TI - Search for a sex pheromone in Triatoma mazzottii (Hemiptera: Reduviidae). AB - Hexane extracts of volatile substances from sexually mature male and female Triatoma mazzottii Usinger, collected with cold glass trap (-10 degrees C) and evaluated in a wind tunnel, demonstrated the absence of a sex pheromone. The females failed to secrete a liquid from the sixth and seventh abdominal sternite. PMID- 1875378 TI - Chrysomya megacephala (Diptera: Calliphoridae) has reached the continental United States: review of its biology, pest status, and spread around the world. AB - Chrysomya megacephala (F.), an Old World calliphorid of considerable public health importance, was first discovered in Brazil in 1977 and is now widely distributed in Latin America. Reports that this species has become established in southern California, and the collection of a specimen in Texas, suggest that C. megacephala may be expanding its range rapidly in North America. The biology and worldwide spread of this pest are reviewed to alert entomologists and public health workers to this growing threat. PMID- 1875379 TI - Gonotrophic development in the rodent bot fly Cuterebra fontinella (Diptera: Oestridae). AB - The gonotrophic development of Cuterebra fontinella Clark begins after the larval pupal molt, the point at which winter diapause often occurs in many Cuterebra spp. Adult females emerge with their eggs at stage 3 and require an additional 5 d to complete oogenesis. Other species of Cuterebra also may have similar developmental sequences and require a period of several days after eclosion to complete development of their ova. PMID- 1875380 TI - Human envenomization by Plectreurys tristis Simon (Araneae: Plectreuridae): a case report. AB - A case of human envenomization by a plectreurid spider, Plectreurys tristis Simon, is reported for the first time. The patient was bitten on the calf of the leg and initially experienced pain, edema, and slight pallor at the bite site. Numbness persisted for approximately 1 h in the affected leg. Symptoms resolved without specific treatment, and no significant sequelae were observed. PMID- 1875381 TI - Problems and issues in developing a cochlear implant programme for children. AB - This paper considers the implications for deaf children and their families of the establishment of a cochlear implant programme for children. The importance of recognizing that implantation affects the whole child and that a multidisciplinary whole-child approach is necessary is stressed. The elements of a cochlear implant support service for families with deaf children are described. PMID- 1875382 TI - A family of neuromuscular stimulators with optical transcutaneous control. AB - A family of miniature implantable neuromuscular stimulators has been developed using surface-mounted Philips 4000-series integrated circuits. The electronic components are mounted by hand on printed circuits (platinum/gold on alumina) and the electrical connections are made by reflow soldering. The plastic integrated circuit packages, ceramic resistors and metal interconnections are protected from the body fluids by a coating of biocompatible silicone rubber. This simple technology provides reliable function for at least 4 months under implanted conditions. The circuits have in common a single lithium cell power-supply (3.2 V) and an optical sensor which can be used to detect light flashes through the skin after the device has been implanted. This information channel may be used to switch the output of a device on or off, or to cycle through a series of pre-set programs. The devices are currently finding application in studies which provide an experimental basis for the clinical exploitation of electrically stimulated skeletal muscle in cardiac assistance, sphincter reconstruction or functional electrical stimulation of paralysed limbs. PMID- 1875383 TI - A preliminary report on a new hydraulic sphincter for controlling urinary incontinence. AB - A new pressure-regulated artificial urinary sphincter (AUS) has been developed which overcomes many of the deficiencies of earlier devices. This implantable AUS comprises a circular occluder cuff and the means to inflate and deflate through a pressure-regulated valve. The device is made from medical-grade silicone rubber and filled with radio-opaque isotonic fluid. A few days before surgery the implant is coated on the outside with an antibiotic-loaded silicone rubber solution. Tests have shown that the regulated pressure was very easily adjusted in situ by injecting or withdrawing the hydraulic fluid through a hypodermic needle penetrating a self-sealing filling port. When set, the regulated pressure remained very stable. The mechanism by which cuff pressure was increased to overcome stress incontinence worked well. Of the five earlier devices (AUS Mk I) implanted, none has survived without mechanical failure. The two latest implants (Mk II), which were rigorously tested for defects before implantation, have been more successful. PMID- 1875384 TI - Ceramic bearing surfaces in total artificial joints: resistance to third body wear damage from bone cement particles. AB - Studies of explanted Charnley hip prostheses have shown damage or scratching of the polished stainless steel femoral heads. This surface damage is probably due to third body wear by bone cement particles. Damaged femoral heads will produce increased wear rates of ultra high molecular weight polyethylene (UHMWPE) acetabular cups. Sliding wear tests carried out in the laboratory have shown that alumina ceramic counterfaces are more resistant to third body damage from bone cement particles than stainless steel counterfaces. The use of the ceramic femoral heads in artificial hip joints will help to preserve the smooth surface finish on the femoral bearing surface, which is necessary to ensure low wear rates of the UHMWPE cup throughout the lifetime of the prosthesis. PMID- 1875385 TI - In vitro evaluation of an implantable left ventricular assist device. AB - The development of implantable left ventricular assist devices (LVADs) has almost reached the stage of providing permanent circulatory support in patients who are unsuitable for, or denied, the transplant option. As part of our ongoing haemodynamic evaluation of the Thermo Cardiosystems Inc. (Boston, USA) Mark 14 pneumatic LVAD, pressure-volume loops have been produced from in vitro studies using a modified National Heart Lung and Blood Institute (NHLBI, USA) mock circulatory loop. These studies have demonstrated that during certain phases of the pump cycle non-physiologically high and low pressures are generated within the LVAD. Such abnormal pressures may damage either the bioprosthetic valves in the LVAD or the native heart, and may have adverse effects on cardiovascular control mechanisms. PMID- 1875386 TI - The implanted electrical resistance strain gauge: in vitro studies on data integrity. AB - The aim of this research is to investigate, and thus counter, the adverse effects of tissue fluid ingress on the performance of the electrical resistance strain gauge when used in ascertaining in vivo loading on a spinal implant. Moisture absorption has been minimized by adopting maximum metallic coverage in a package comprising stainless steel foil on vacuum-injected pacemaker grade epoxide. In a simulation of the implanted environment, cyclic strain wet endurance testing in saline suggests that, in the body, the fall in indicated quasi-dynamic strain would be less than 1.5% at 24 weeks post-operation (the longevity needed to span adequately the bony fusion phase). This implies that stiffening of the fusion mass will be deducible to a similar accuracy (from stepped-load exercises), in which creep is a secondary effect. However, crucial information (from quasi static (passive) studies) regarding remodelling and load-sharing processes would be subject to a total signal error (primarily due to grid corrosion) in excess of 16% by 24 weeks, since long-term drifts are not inherently cancelled. Signal compensation is therefore additionally required, and an approximate empirical characterization of total error versus time has been derived. PMID- 1875387 TI - Controlling radio frequency interference from neurological prostheses. AB - The simplest kind of radio frequency (RF) coupled neurological prosthesis, in which a burst of RF, generated by the external equipment, provides the stimulus energy via a passive implanted receiver, is the most troublesome in respect of RF interference (RFI). Because the low ratio of pulse duration to interpulse interval is usually the case, the peak power transmitted is necessarily high, of the order of watts. This paper outlines a series of measurements by which the mode of RFI generation by a typical external equipment was precisely identified, enabling rational and appropriate countermeasures to be taken. PMID- 1875388 TI - Rapid communication: cleaning up a Hartley oscillator. AB - In a programme to understand, and learn to control, radiofrequency interference from neurological prostheses, it was discovered that a harmless-looking Hartley oscillator (one type of harmonic oscillator) generated a forest of harmonics extending to 1 GHz. These harmonics were not difficult to eliminate. The point of this paper is to emphasize that, given the selection of instruments used by most development engineers, the harmonics would probably have been missed. PMID- 1875389 TI - Direct Gram's stain of vaginal discharge as a means of diagnosing bacterial vaginosis. AB - The diagnosis of bacterial vaginosis (BV) by direct gram-stained smear of vaginal discharge was evaluated in 90 consecutive patients. Vaginal secretions from 20 healthy female volunteers were also examined. All specimens were examined by culture for growth of Gardnerella vaginalis and Lactobacillus spp. Only 35 (38.9%) of the patients with vaginal discharge satisfied the clinical diagnosis of BV. The vaginal gram-stained smear from all these 35 patients contained typical gardnerella morphotypes characteristic of BV and G. vaginalis was isolated from all of them as well as from a further 10 patients who did not satisfy the criteria for diagnosis of BV. The semi-quantitative assessment of gardnerella morphotypes was found to correlate positively with the semi quantitative assessment of G. vaginalis growth by culture (p less than 0.0001). There was a strong inverse relationship between the quantity of lactobacillus and gardnerella morphotypes. Direct gram-staining of smears should facilitate the diagnosis of BV for clinicians with minimum need for confirmation by culture, particularly in a third world setting with few or no laboratory facilities. PMID- 1875390 TI - An improved selective medium for the isolation of Escherichia coli O157. AB - Sorbitol-MacConkey medium has become widely used for the isolation of verotoxigenic (VT+) Escherichia coli O157. However, many organisms other than VT+ E. coli O157, especially other serogroups of E. coli and Proteus spp., may not ferment sorbitol, and thus may be confused initially with VT+ E. coli O157. Rhamnose is not fermented by VT+ E. coli O157, but is by most sorbitol non fermenting E. coli of other serogroups. Cefixime is a cephalosporin antibiotic that is more active against Proteus spp. than against E. coli. Inclusion of rhamnose and cefixime in sorbitol-MacConkey agar improves its selectivity for the isolation of VT+ E. coli O157. PMID- 1875391 TI - Selected faecal bacteria and nutrients essential for antagonism of Salmonella typhimurium in anaerobic continuous flow cultures. AB - As few as five of the species of bacteria commonly found in human faeces- Escherichia coli, Enterobacter aerogenes, Enterococcus faecalis, Bacteroides ovatus and Fusobacterium varium--when grown together in anaerobic continuous flow cultures exerted antagonistic effects on Salmonella typhimurium as great as those given by mixed bacteria from extracts of human faeces. In a single culture, the population of S. typhimurium was c. 10(8) cfu/ml but in mixed cultures with the five antagonistic bacteria or mixed faecal bacteria it was reduced to c. 10(3) cfu/ml. Antagonism appeared to be the result of competition for the growth limiting amino acids, arginine, serine, threonine and aspartic acid. Optimal manifestation of antagonism required the presence of carbon sources fermentable only by antagonistic bacteria, such as lactose 0.1%, w/v, sucrose 0.1% (w/v) and starch 0.2-0.3% w/v. These carbohydrates promoted the growth of the antagonistic bacteria, particularly E. coli and B. ovatus. However, an increase in concentration by several fold of any one of four growth-limiting amino acids in the medium diminished the antagonistic effects and the population of S. typhimurium rose 10(2)-10(3)-fold. PMID- 1875392 TI - A study of the antigenic composition of the fragilis group of Bacteroides. AB - Representative strains of 22 serotypes of the fragilis group of Bacteroides and four non-fragilis control strains of B. melaninogenicus, B. disiens, B. bivius and Fusobacterium nucleatum were tested by SDS-PAGE and immunoblotting with hyperimmune rabbit sera. SDS-PAGE showed 25 polypeptide bands but, after immunoblotting, 24 antigenic bands were observed in various combinations in all the strains. Three of these were detected only in the control strains, whereas six others were present in different combinations in all strains of the fragilis group but were not present in the controls. Cluster analysis of the antigenic bands showed that the controls were antigenically different from the fragilis group strains. Strains of the fragilis group from the same geographic localities grouped in single clusters; most faecal isolates and NCTC strains appeared separate. There was no correlation between the species of Bacteroides and their antigenic structure. SDS-PAGE with immunoblotting is a superior technique for typing the fragilis group of Bacteroides. Specific antigens have been identified which may be used in the serodiagnosis of infection with these organisms. PMID- 1875393 TI - Characterisation and functional aspects of monoclonal antibodies specific for surface proteins of coagulase-negative staphylococci. AB - Mouse monoclonal antibodies (MAbs) raised against whole cells of Staphylococcus epidermidis strain 354 were characterised morphologically and functionally. Nine MAbs showed strong reactivity with coagulase-negative staphylococci (CNS). Only two MAbs were specific for CNS; both belonged to the IgG1 subclass, and one, MAb 36.4, reacted only with the strain used for immunisation. In immunoblotting, both CNS-specific MAbs 36.3 and 36.4 reacted strongly with cell-wall protein bands of 220 Kda of S.epidermidis strain 354 and weak reactivity was observed with a 110 Kda band. MAb 36.3 reacted also with 220-230 Kda bands of two other S.epidermidis strains (291 and ATCC 35984) and a 160-180 Kda band of S.epidermidis strain 354. Only MAb 36.4 promoted phagocytosis of strain 354 by polymorphonuclear leucocytes (PMNL) and monocytes, whereas MAb 36.3 and the other MAbs lacked this activity. Opsonisation of S. epidermidis with MAb 36.4 in the presence of complement enhanced uptake by PMNL, but not by monocytes. Furthermore, S.epidermidis strain 354 opsonised with MAb 36.4 induced chemiluminescence of PMNL. Immuno-gold electronmicroscopy with both MAbs 36.3 and 36.4 demonstrated a homogeneous distribution of gold particles on the surface as well as close to the surface of S.epidermidis. PMID- 1875394 TI - Transfer of resistance determinants from a multi-resistant Staphylococcus aureus isolate. AB - The clinical isolate Staphylococcus aureus WBG1024 was resistant to cadmium, benzyl penicillin, kanamycin, neomycin, streptomycin, tetracycline and trimethoprim and harboured a conjugative plasmid pWBG637 (34.5 kb) and non conjugative plasmids of 23.8, 4.4, 2.8 and 1.9 kb. Transduction and mixed-culture transfer experiments demonstrated that the 4.4-kb plasmid (pWBG632) encoded resistance to tetracycline and the 23.8-kb plasmid (pWBG628) encoded resistance to cadmium, benzyl penicillin, kanamycin, neomycin and streptomycin. The conjugative plasmid pWBG637 was able to mobilise a further 4.4-kb plasmid (pWBG633) encoding streptomycin resistance and recombined with the multiresistance plasmid pWBG628 to produce transconjugantes of various resistance phenotypes. PMID- 1875395 TI - Usefulness of three probes in typing isolates of methicillin-resistant Staphylococcus aureus (MRSA). AB - Fifty-nine epidemiologically unrelated methicillin-resistant Staphylococcus aureus (MRSA) isolates from different geographical areas and 23 phage-type 77 MRSA isolates from France were investigated. Cellular DNA, digested with restriction endonucleases EcoRI or HindIII, was probed with plasmids carrying the gene encoding 16S rRNA (pBA2), the gene aacA-aphD (pSF815A) and the gene aacA aphD plus part of IS256 (pIP1307). When probed with pBA2, most of the unrelated isolates displayed the same hybridisation pattern. A greater diversity in patterns was detected in gentamicin-resistant strains with the two other probes. The most accurate fingerprinting of these isolates was obtained with the probe pIP1307. Moreover, this probe appeared to be useful for tracing the phage-type 77 epidemic MRSA isolates widespread in French hospitals. PMID- 1875396 TI - Antimicrobial susceptibility testing of mycoplasmas by ATP bioluminescence. AB - The susceptibility of 72 mycoplasmas to a range of antimicrobial agents was assessed in a 6-h ATP bioluminescence system. ATP was assayed with the Amerlite Analyser. Correlation with conventionally determined MICs was excellent for erythromycin and tetracycline even at 3 h. However, for ciprofloxacin, correlation was poor unless incubation was extended to 6 h. PMID- 1875397 TI - Adherence of Serratia marcescens in the pathogenesis of urinary tract infections in diabetic mice. AB - The adherence of Serratia marcescens to bladder epithelial cells of mice with alloxan-induced diabetes was studied. S. marcescens adhered more strongly to the bladder epithelial cells of diabetic mice than to those of normal mice both in vitro and in vivo. The susceptibility of diabetic mice to urinary tract infection may be due to an increased adhesive capacity of bladder epithelial cells. PMID- 1875398 TI - Detection of Borrelia burgdorferi in cerebrospinal fluid by the polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used to amplify specific DNA sequences from different clinical isolates of Borrelia burgdorferi and from cerebrospinal fluid (CSF) of two patients with Lyme disease of the central nervous system. The amplification products were separated by polyacrylamide gel electrophoresis and visualised by ethidium bromide staining. The definitive identification of amplified DNA as a part of the B. burgdorferi flagellin gene was achieved by hybridisation to a 40-base oligonucleotide probe complementary to a part of the spirochaetal gene but not to the primers. Attempts to cultivate borreliae from either patient were unsuccessful and one patient had no serological marker in serum or CSF to indicate borreliosis. Clinical symptoms of both patients regressed with antibiotic therapy. The PCR system is a powerful and rapid technique to amplify flagellin gene sequences from CSF of patients with neuroborreliosis. Only one-tenth of the time needed for cultivation was required from CSF sampling to diagnosis. Gene amplification might, for the first time, allow effective monitoring of therapy for patients with Lyme disease of the central nervous system. PMID- 1875399 TI - HCO3(-)-coupled Na+ influx is a major determinant of Na+ turnover and Na+/K+ pump activity in rat hepatocytes. AB - Recent studies in hepatocytes indicate that Na(+)-coupled HCO3- transport contributes importantly to regulation of intracellular pH and membrane HCO3- transport. However, the direction of net coupled Na+ and HCO3- movement and the effect of HCO3- on Na+ turnover and Na+/K+ pump activity are not known. In these studies, the effect of HCO3- on Na+ influx and turnover were measured in primary rat hepatocyte cultures with 22Na+, and [Na+]i was measured in single hepatocytes using the Na(+)-sensitive fluorochrome SBFI. Na+/K+ pump activity was measured in intact perfused rat liver and hepatocyte monolayers as Na(+)-dependent or ouabain suppressible 86Rb uptake, and was measured in single hepatocytes as the effect of transient pump inhibition by removal of extracellular K+ on membrane potential difference (PD) and [Na+]i. In hepatocyte monolayers, HCO3- increased 22Na+ entry and turnover rates by 50-65%, without measurably altering 22Na+ pool size or cell volume, and HCO3- also increased Na+/K+ pump activity by 70%. In single cells, exposure to HCO3- produced an abrupt and sustained rise in [Na+]i from approximately 8 to 12 mM. Na+/K+ pump activity assessed in single cells by PD excursions during transient K+ removal increased congruent to 2.5-fold in the presence of HCO3-, and the rise in [Na+]i produced by inhibition of the Na+/K+ pump was similarly increased congruent to 2.5-fold in the presence of HCO3-. In intact perfused rat liver, HCO3- increased both Na+/K+ pump activity and O2 consumption. These findings indicate that, in hepatocytes, net coupled Na+ and HCO3- movement is inward and represents a major determinant of Na+ influx and Na+/K+ pump activity. About half of hepatic Na+/K+ pump activity appears dedicated to recycling Na+ entering in conjunction with HCO3- to maintain [Na+]i within the physiologic range. PMID- 1875400 TI - Permeance of Cs+ and Rb+ through the inwardly rectifying K+ channel in guinea pig ventricular myocytes. AB - Inward currents carried by external Cs, Rb, NH4 and K through the IK1 channel were studied using a whole-cell voltage clamp technique. Cs, NH4, and Rb currents could be recorded negative to -40 mV following depolarizing prepulses (greater than or equal to 0 mV and 200-1000 msec in duration). The current activation displayed an instantaneous component followed by a monoexponential increase (tau a) to a peak amplitude. Subsequent inactivation was fit by a single exponential, tau ia. With hyperpolarization, tau a and tau ia decreased e-fold per 36 and 25 mV, respectively. In Ca-free external solutions (pipette [Mg] approximately 0.3 mM), inactivation was absent, consistent with the hypothesis that inactivation represents time- and voltage-dependent block of Cs, NH4, and Rb currents by external Ca. The inactivation and degree of steady-state block was greatest when Cs was the charge carrier, followed by NH4, and then Rb. K currents, however, did not inactivate in the presence of Ca. Na and Li did not carry any significant current within the resolution of our recordings. Comparison of peak inward current ratios (Ix/IK) as an index of permeability revealed a higher permeance of Cs (0.15), NH4 (0.30), and Rb (0.51) relative to K (1.0) than that obtained by comparing the steady-state current ratios (Cs:NH4:Rb:K approximately 0.01:0.06:0.21:1.0). At any given potential, tau a was smaller the more permeant the cation. In the absence of depolarizing prepulses, the amplitude of tau a was reduced. Divalent-free solutions did not significantly affect activation in the presence of 0.3 mM pipette [Mg]. When pipette [Mg] was buffered to approximately 50 microM, however, removal of external Ca and Mg lead to a four- to fivefold increase in Cs currents and loss of both time-dependent activation and inactivation (reversible upon repletion of external Ca). These results suggest that (i) permeability ratios for IK1 should account for differences in the degree to which monovalent currents are blocked by extracellular Ca and (ii) extracellular or intracellular divalent cations contribute to the slow phase of activation which may represent either (a) the actual rate of Mg or Ca extrusion from the channel into the cell, a process which may be enhanced by repulsive interaction with the incoming permeant monovalent cation or (b) an intrinsic gating process that is strongly modulated by the permeant monovalent ion and divalent cations. PMID- 1875401 TI - Osmotic effects of protein polymerization: analysis of volume changes in sickle cell anemia red cells following deoxy-hemoglobin S polymerization. AB - Polymerization-depolymerization of proteins within cells and subcellular organelles may have powerful osmotic effects. As a model to study these we analyzed the predicted volume changes following hemoglobin (Hb) S polymerization in sickle cell anemia (SS) red cells with different initial volumes. The theoretical analysis predicted that dehydrated SS red cells may sustain large polymerization-induced volume shifts whose direction would depend on whether or not small solutes were excluded from polymer-associated water. Experiments with SS cells from promptly fractionated venous blood showed oxygenation-induced swelling, maximal in the densest cells, in support of nonexclusion models. The predicted extent of cell dehydration on polymerization was strongly influenced by factors such as the dilution of residual soluble Hb and the increased osmotic contribution of Hb in cells dehydrated by salt loss, largely overlooked in the past. The osmotic effects of polymer formation may thus play an important part in microcirculatory infarction by dense SS cells, as they become even denser and stiffer during deoxygenation in the capillaries. PMID- 1875402 TI - Perceived personal immunity to the consequences of drinking alcohol: the relationship between behavior and perception. AB - Heavy drinkers, moderate drinkers, light drinkers, and nondrinkers were asked to rate a variety of negative health and social consequences of using alcohol. Subjects made probability ratings for fictional others who were heavy, moderate, or light drinkers or nondrinkers. Subjects also made probability ratings for themselves as hypothetical heavy, moderate, or light drinkers or nondrinkers and for themselves actually. A pattern of perceived personal immunity was found across groups. Subjects rated fictional others and themselves as hypothetical drinkers to be more likely to experience negative consequences than their actual selves. All groups of subjects (heavy, moderate, and light drinkers and abstainers) rated their actual chances of experiencing negative consequences to be approximately equal. In contrast, heavy drinkers saw the effects of drinking for other heavy drinkers as less likely than did subjects who had light or abstinent drinking patterns who rated fictional heavy drinkers. These findings suggest that individuals who drink more tend to deny the potential harm that may result from alcohol consumption. Short-term social consequences were viewed as most likely to occur. Long-term consequences were perceived as least likely to occur. PMID- 1875403 TI - Parental acceptability of treatments for children's hypercholesterolemia. AB - This study examined the acceptability ratings of three alternative treatments applied to case descriptions which varied in their level of problem severity. Evaluations were provided by 40 parents seeking services in a Pediatric Preventive Cardiology Clinic for treatment of their children's hypercholesterolemia. Results indicated that both diet and diet plus goal setting were rated as significantly more acceptable than medication. Ratings of diet and diet plus goal setting did not vary as a function of problem severity, however, medication was rated as more acceptable when applied to a more severe case example, as opposed to a mild case example. Findings are discussed in relation to the clinical significance of these findings and the need for future research. PMID- 1875404 TI - Measuring contraceptive values: an alternative approach. AB - Previous assessments of individuals' values for various contraceptive consequences have employed one of four methodologies: free elicitation, direct ratings, multiple regression, or factor analysis. All four methodologies are flawed because they produce group rather than individual values, relying on rating scales, and fail to incorporate information regarding consequence trade offs. Axiomatic conjoint measurement is proposed as an alternative methodology and used to determine individuals' values for a selected set of contraceptive consequences at two stages of the family-planning career. PMID- 1875405 TI - Preventing relapse in obesity through posttreatment maintenance systems: comparing the relative efficacy of two levels of therapist support. AB - The present study compared the relative effectiveness of a therapist-supported maintenance condition with a minimal contact maintenance condition in preventing relapse following an obesity treatment program. Thirty-two subjects who completed an initial 12-week cognitive/behavioral plus aerobic exercise treatment program were matched on absolute weight loss and randomly assigned to one of two maintenance conditions. Subjects were assessed at pretreatment, posttreatment, and 3, 6, and 12 months following posttreatment using measures of weight, blood pressure, and depression. Three- and six-month follow-up results indicated that subjects who participated in the therapist-supported maintenance group continued to lose weight and/or maintained therapy-induced weight loss to a greater degree than control subjects. At the 12-month follow-up assessment therapist-supported subjects maintained therapy-induced weight loss better than the control subjects. These findings suggest that maintenance programs which provide continued contact emphasizing relapse prevention training may be an important adjunct in the maintenance of therapy-induced weight loss. PMID- 1875407 TI - Agreements signed to test foods for cancer prevention. PMID- 1875406 TI - Efficacy of a self-directed behavioral health change program: weight, body composition, cardiovascular fitness, blood pressure, health risk, and psychosocial mediating variables. AB - This study assessed the efficacy of a comprehensive behavioral health program designed to promote self-initiated change in overweight healthy middle-aged adults (M = 49 years). Three treatment groups (total n = 25) differing in type of social support provided (i.e., group plus professional versus group plus peer versus group only) received 13 treatment sessions and 6 maintenance sessions scheduled over a full year. A self-directed change intervention taught several cognitive-behavioral techniques as they applied to exercise adherence, weight reduction/maintenance, and stress management. Combined treatment groups (n = 25) improved significantly more than an assessment only control group (n = 9) in weight, percentage body fat, cardiovascular fitness, exercise adherence, health risk appraisal, chronic tension (MBHI, scale A), and systolic and diastolic blood pressure at both post-treatment and 6-month follow-up assessments. Self motivation, group treatment attendance, and health-risk appraisal significantly related (r's = .30-.56) to several posttreatment and follow-up measures of behavioral health change. No significant differences were found among the three treatment groups on any of the outcome measures. PMID- 1875408 TI - 1971-1991: quality of life gains increased attention. PMID- 1875409 TI - Supermarket computer gives free diet advice and easy recipes. PMID- 1875410 TI - NIH appropriations bills moving through House, Senate. PMID- 1875411 TI - President's panel examines cancer among the poor. PMID- 1875412 TI - How many human cancer genes? PMID- 1875413 TI - Randomized dose-searching phase ILE/II trials of fractionation in radiation therapy for cancer. AB - This article describes a new design, phase ILE/II dose searching, used in four prospective, randomized, multicenter clinical trials of escalating total doses of hyperfractionated radiation. This design combines an experimental protocol with a statistical application of ranking and selection theory. Its purpose was to identify (within a certain margin of error) a dose that achieved the highest rate of clinical response from a set of doses that were tolerable in terms of both acute (within 90 days) and late (more than 90 days) toxic effects (LE). We calculated the number of patients required to reliably test toxicity under various assumptions. To determine the maximum tolerated total dose for hyperfractionated radiation, we randomly assigned patients with tumors that responded to radiation therapy in a dose-dependent manner from four body sites (lung, upper respiratory and digestive tract, bladder, and brain) to one of three regimens receiving total doses (D1, D2, or D3) differing by increments of 4.8 Gy. All patients received two fractions of 1.2 Gy each (separated by 4-6 hours) daily 5 days a week. The lowest total dose was set at the level considered tolerable with standard once-a-day radiation therapy. We tested tumor responses and late toxic effects of higher doses by assigning patients to these three regimens until acute effects and early estimates of late effects were found to be acceptable for the highest dose D3; thereafter, regimen D1 was closed, and additional patients were assigned to D2, D3, and D4 (an escalated total dose greater than D3 by an increment of 4.8 Gy). The assignment of patients was performed in a weighted manner (1:1:2), so that greater numbers were assigned to the highest dose regimen (whether D3 or D4) to allow rapid evaluation of the feasibility of the highest dose. PMID- 1875414 TI - Cancer risk after iodine-131 therapy for hyperthyroidism. AB - Cancer incidence was studied in 10,552 patients (mean age, 57 years) who received 131I therapy (mean dose, 506 MBq) for hyperthyroidism between 1950 and 1975. Follow-up on these patients was continued for an average of 15 years. Record linkage with the Swedish Cancer Register for the period 1958-1985 identified 1543 cancers occurring 1 year or more after 131I treatment, and the standardized incidence ratio (SIR) was 1.06 (95% confidence interval = 1.01-1.11). Significantly increased SIRs were observed for cancers of the lung (SIR = 1.32; n = 105) and kidney (SIR = 1.39; n = 66). Among 10-year survivors, significantly elevated risks were seen for cancers of the stomach (SIR = 1.33; n = 58), kidney (SIR = 1.51; n = 37), and brain (SIR = 1.63; n = 30). Only the risk for stomach cancer, however, increased over time (P less than .05) and with increasing activity administered (P = not significant). The risk for malignant lymphoma was significantly below expectation (SIR = 0.53; n = 11). Overall cancer risk did not increase with administered 131I dose or with time since exposure. The absence of any increase in leukemia adds further support to the view that a radiation dose delivered gradually over time is less carcinogenic than the same total dose received over a short time. Only for stomach cancer was a possible radiogenic excess suggested. PMID- 1875415 TI - Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study. AB - Four hundred eleven women with metastatic breast cancer were randomly assigned to receive either 60 mg/m2 doxorubicin (130 patients), 320 mg/m2 bisantrene (146 patients), or 14 mg/m2 mitoxantrone (135 patients). The doses were given intravenously every 3 weeks with a cross-over design to determine their relative efficacy and toxicity. To be eligible, patients must have had one previous chemotherapy regimen, and patients who were estrogen receptor positive must have failed endocrine therapy. There were 365 patients assessable for response and 399 assessable for toxic effects. The median age was 57 years; 18% were premenopausal or perimenopausal. Visceral dominant disease was present in 66% of the patients. Ninety-seven percent of the patients had a disease-free interval from diagnosis to first recurrence of less than 1 year. The response rate was 28% with doxorubicin, 13% with bisantrene, and 14% with mitoxantrone (P = .004). Median time to treatment failure was 133 days with doxorubicin, 66 days with bisantrene, and 68 days with mitoxantrone (logrank P = .06). The median survival was 315 days for doxorubicin, 290 days for bisantrene, and 177 days for mitoxantrone (logrank P = .04), although survival at 2 years was similar for all three agents. There were five responses in the 66 patients crossed over to doxorubicin and one response each for patients crossed over to bisantrene (39 patients) or mitoxantrone (63 patients). Toxicity leading to discontinuance of therapy was more common with doxorubicin, and discontinuance of therapy was due primarily to patient's request or cardiotoxicity. The major dose-limiting toxic effect for all three agents was leukopenia. Nausea and vomiting, mucositis, and alopecia were more severe with doxorubicin. Congestive heart failure developed in nine patients treated with doxorubicin, zero patients treated with bisantrene, and two patients treated with mitoxantrone. A decrease in the left ventricular ejection fraction, as defined by moderate to severe Alexander grade changes, was more common in patients treated with doxorubicin (doxorubicin-treated patients = 20%, bisantrene treated patients = 5%, and mitoxantrone-treated patients = 10%). This study demonstrates that bisantrene and mitoxantrone have only modest activity in metastatic breast carcinoma. The activity of doxorubicin is greater than that of the other two agents, but at a cost of increased toxicity. PMID- 1875416 TI - Glutathione content in human bone marrow and circadian stage relation to DNA synthesis. AB - DNA synthesis and contents of reduced glutathione (GSH) and oxidized glutathione were determined every 4 hours during a 24-hour period in 70 human bone marrow samples from 10 healthy males. The mean GSH contents during the sampling periods were low, varying from 1.94 to 3.27 nmol/mg protein between the subjects; the mean values for all samples were 2.54 +/- 0.06 nmol/mg protein. The GSH content varied markedly within the individual according to circadian stage (31.0% to 90.2%; mean, 51.4%). Between individuals the mean percentage of cells in DNA synthesis varied from 10.6% to 14.5%, but there was an intraindividual circadian stage-dependent variation, ranging from 48.9% to 274.0% (mean, 126.6%), relative to the lowest value. After adjustment for a slight phase difference between GSH content and DNA synthesis observed for some of the subjects, a statistically significant correlation was found between the GSH content and the fraction of cells in DNA synthesis. The myelosuppressive effect of many chemotherapeutic agents assumed to be detoxified by GSH-dependent mechanism(s) should be considered in the light of the low GSH content in human bone marrow, the circadian variation of DNA synthesis, and the circadian stage-dependent relationship of the GSH content and DNA synthesis. PMID- 1875417 TI - Colorectal cancer screening. PMID- 1875418 TI - Ocular phototoxicity. PMID- 1875419 TI - Chronic obstructive pulmonary disease in blacks and whites: pulmonary function norms and risk factors. AB - Chronic obstructive pulmonary disease (COPD) and asthma are significant causes of illness and death in blacks. Racial differences in normal values of pulmonary function tests must be considered in both patient care and research. Assessment of risk factors is an important part of COPD management and prevention. An extensive review of data from the National Center for Health Statistics and from other population-based studies confirmed lower lung volumes in blacks compared to whites. However, the ratio of forced expiratory volume in 1 second to forced vital capacity was not lower in blacks; racial differences in flow rates were inconsistently reported. Thoracic dimensions were smaller in blacks than in whites in healthy populations. The cause and the physiologic and pathophysiologic significance of these racial differences are unknown. Population-based studies in blacks have firmly established only age and cigarette smoking as risk factors for COPD other than asthma. In 1987, 43% of black men aged 45 and older smoked cigarettes compared to only 30% of white men. Further research is needed on racial differences in pulmonary function and the effects of multiple risk factors to enhance understanding of COPD etiology and prevention. More vigorous smoking prevention and cessation efforts should be targeted for blacks by physicians and public health organizations. PMID- 1875420 TI - The need for a standard national immunization record. AB - Perhaps the most significant link in achieving the nation's immunization objectives is the extent of parental knowledge. Admittedly, this is a weak link. The 1990 federal objectives calling for an official format using common guidelines for completion of immunizations, though well-conceived, has not been used exclusively by health care givers. The lack of accord has permitted the proliferation of many different immunization records that are not only confusing to parents, but also to health care providers at times. A standard national immunization record could be an essential element in strengthening the weak link of parental knowledge of immunizations and stressing the importance of preserving such a record for a lifetime. PMID- 1875421 TI - The role of topical thrombin in skin grafting. AB - A prospective study to evaluate the efficacy of thrombin as a hemostatic agent in burn patients was conducted on 24 patients undergoing debridement and skin grafting. All patients also acted as their own control. Results showed a 43.5% reduction in bleeding on the thrombin-treated sites compared with the control sites. There was no adverse effect on the rate of wound healing from the thrombin, and no difference in the nature of the scar seen at the thrombin treated site compared with the control site. PMID- 1875422 TI - Mandibular fractures in an American inner city: the Harlem Hospital Center experience. AB - A retrospective study of 116 patients treated at Harlem Hospital for mandibular fractures between 1984 and 1987 was performed. Men comprised 84% of the population studied. The mechanisms of injury were assault with fists and blunt objects (33%), falls (10%), kicking (3%), penetrating injuries (3%), and vehicular accidents (1%). The body of the mandible (46%) and the angle (22%) were the most common fracture sites. Intermaxillary fixation with arch bars was the most frequent method of treatment (55%), followed by open reduction and internal fixation (33%). The complication rate with open reduction was relatively low (15%) despite the fact that 73% of these patients were heavy drug or alcohol abusers with documented poor oral hygiene. This study further substantiates the findings that in the poor inner cities, blunt trauma from drug-related violence has become the major cause of mandibular fracture. Treatment of these patients should include prophylactic broad-spectrum antibiotics, improved oral hygiene, and supplemental nutrition. PMID- 1875423 TI - Clinical assessment of gestational age: a comparison of two methods. AB - The ratio of fundal height (FH) to maternal abdominal length (MAL) was defined as percentage of maternal abdominal length (PMAL) and compared to FH alone in 100 consecutive uncomplicated pregnancies from the 18th week of gestation to delivery at term. Reference graphs for fetal growth evaluation were developed using these two clinical methods. The predictive value of each technique was assessed by comparing gestational age estimates in 29 additional patients at various gestational ages. The correlation coefficient between the known gestational ages and estimates by the PMAL method was .86, and between known gestational ages and estimates by the FH method, .94. Twenty more patients were evaluated by three obstetricians in a double-blind fashion to determine gestational ages by each technique. The average deviation from the real gestational age varied from 2.07 to 3.14 weeks using the FH method, and from 2.82 to 3.97 weeks using the PMAL graph. It was concluded that FH measurement correlates better with gestational age than its ratio to the MAL. PMID- 1875424 TI - Oral mucosa pigment changes in heavy drinkers and smokers. AB - The preliminary observation that heavy drinking and smoking produced oral mucosal changes consisting of splotchy areas of depigmentation surrounded by hyperpigmentation was tested. The study population was comprised of 52 patients from an alcohol detoxification ward, who were compared with 54 patients from psychiatric inpatient and day hospital services. Structured interviewing was developed for both samples of patients who met either diagnostic criteria for alcohol abuse or dependence, or criteria for alcoholism on the Short Form of the Michigan Alcohol Screening Test, and were identified as nonsmokers or as those who smoked one to three or more packs of cigarettes a day. Photographs of the inner surface of the lips, oral mucosa, and gingivae independently were rated for severity of oral pigment change by two raters blind to a patient's alcohol or smoking history. This study demonstrates that reported observable oral pigment changes identify patients who are heavy smokers and drinkers, and may be a useful diagnostic sign. PMID- 1875426 TI - Keloid formation on palmar surface of hand. AB - Keloid formation is never seen on the palms of the hands. The occurrence of a large keloid forming after a surgical procedure performed in the palmar surface of the hand of a black female patient is described. This is the first known case report in English literature. PMID- 1875425 TI - Comparative histochemical studies of rats infected with a pathogenic and nonpathogenic trypanosome. AB - Histochemical variations in tissues from rats inoculated with Trypanosoma lewisi and Trypanosoma rhodesiense were investigated. During peak parasitemia, the liver of rats inoculated with T lewisi showed increased glycogen distribution. However, glycogen depletion was noted in the liver and spleen of animals inoculated with living cells of T rhodesiense. Depletion was very apparent from day 4 to day 10. Throughout the period of observation, only a small amount of lipid infiltration occurred in tissues from animals inoculated with both organisms. Protein tests revealed a normal distribution of protein in tissues. Sections of the liver from rats inoculated with T lewisi showed strong alkaline phosphatase activity on days 7, 10, and 13. Alkaline phosphatase activity for T rhodesiense-infected animals was positive for days 4, 7, and 10. Strong positive reactions for acid phosphatase were observed on days 10 and 13 for some tissues (liver, spleen, and kidney) from rats inoculated with T lewisi. On days 4, 7, and 10, intense staining reactions also were observed for livers and spleens of animals inoculated with T rhodesiense. Regardless of tissues observed, histochemical variations were not observed in animals inoculated with the derivatives (ie, metabolic products and homogenates) of T lewisi and T rhodesiense. PMID- 1875427 TI - Myxedema mimicking myocardial ischemia in a young black male. AB - High elevations of creatine kinase secondary to myxedema in a 29-year-old black male resulted in an erroneous diagnosis of mycardial infarction. PMID- 1875428 TI - Practical causal inference for ecoepidemiologists. AB - Environmental scientists and managers must determine whether a relationship between an environmental factor and an observed effect is causal and respond accordingly. Epidemiologists have, over the past 150 yr, developed a systematic approach to evaluating these relationships. Their criteria for objectively evaluating the relationship between a suspect cause and a chronic disease are (1) probability, (2) time order, (3) strength of association, (4) specificity, (5) consistency on replication, (6) predictive performance, and (7) coherence. These criteria can be used, with little modification, to evaluate associations in relation to diseases in fish and wildlife suspected to be caused by exposure to chemical pollutants. Some populations of fish and wildlife are members of the same guilds as subpopulations of humans. Investigations of chemically induced disease in these sentinel populations of fish and wildlife may identify the potential risks posed to these human subpopulations. Evidence evaluated using the epidemiologic criteria may assist environmental managers to determine whether a substantive case can be made to initiate preventative or remedial action. By applying the null hypothesis, scientists are forced to consider how much information must be ignored to conclude that a causal relationship does not exist. PMID- 1875429 TI - Epidemiology of Great Lakes bald eagles. AB - Historical data are provided to support the hypothesis that organochlorine chemicals introduced into the Great Lakes ecosystem following World War II are the cause of reproductive loss among bald eagles (Haliaeetus leucocephalus) in the basin. This is supported with data on concurrent population fluxes of extrabasin North American bald eagle populations and the European white-tailed sea eagle (Haliaeetus albicillus) where the same chemicals were produced and released. Organochlorine chemicals appear as a unique stress on Great Lakes bald eagle populations when compared with stresses on successful populations of bald eagles continentwide. Shoreline birds bear significantly higher concentrations of these persistent toxics than inland birds. Association between contaminated prey and elevated concentrations of PCBs, DDT, and DDE in Great Lakes bald eagles are presented. A fledging ratio is used to support the hypothesis that maternal prezygotic exposure affects the viability of embryos and chicks. The ratio of the mean number of fledglings per successful territory to the mean number of fledglings per active territory, when the numerator is greater than 1.4, provides an index of exposure to contaminants by parental animals and affected offspring. When the ratio is greater than 2, parental exposure to organochlorine chemicals should be considered. The adverse effects of prezygotic exposure to the same contaminants in other animal species dependent upon Great Lakes fish, and extrabasin bald eagle populations dependent upon contaminated fish, provide consistency to the argument. The mechanism of action of the organochlorine chemicals further strengthens the causal argument indicting DDT, DDE, and PCBs. A strong association between DDT/DDE and bald eagle reproductive success is provided. However, the role of PCBs is not ruled out. Only data for total PCB concentrations in bald eagle tissue are available, and until specific PCB congeners are quantified there will be uncertainty concerning PCB's role in the Great Lakes bald eagle's lack of success. PMID- 1875430 TI - Great Lakes embryo mortality, edema, and deformities syndrome (GLEMEDS) in colonial fish-eating birds: similarity to chick-edema disease. AB - Several species of colonial fish-eating birds nesting in the Great Lakes basin, including herring gulls, common terns and double-crested cormorants, have exhibited chronic impairment of reproduction. In addition to eggshell thinning caused by high levels of DDT and metabolites, the reproductive impairment is characterized by high embryonic and chick mortality, edema, growth retardation, and deformities, hence the name Great Lakes embryo mortality, edema, and deformities syndrome (GLEMEDS). The hypothesis has been advanced that GLEMEDS in colonial fish-eating birds resembles chick-edema disease of poultry and has been caused by exposure to chick-edema active compounds that have a common mode of action through the cytochrome P-448 system. Detailed evidence has been collected from the following three groups of studies on herring gulls in the lower Great Lakes during the early 1970s; Forster's terns in Green Bay, Wisconsin in 1983; and double-crested cormorants and Caspian terns in various locations in the upper Great Lakes from 1986 onwards. It has proved difficult to establish not only the onset of the disease in the various species at various locations but also the period in which chick-edema active compounds were released. Anecdotal evidence suggested that serious egg mortality in Lake Ontario herring gulls first occurred in 1966, through the signs of chick-edema disease were not looked for until 1974. Only indirect evidence is available on the date of the release of one of the presumed causal agents, 2,3,7,8-tetrachlorodibenzo-p-dioxin, but highest levels may have occurred in the early to mid 1960s. More reliable data show that the onset of the improvement of reproduction of Lake Ontario herring gulls coincided with the declines in organochlorine compounds and particularly 2,3,7,8-TCDD and PCB. Similarly, information on the onset of the disease and exposures in the Forster's tern and double-crested cormorants in Green Bay is uncertain but bird banders did not observe deformities until the 1970s, which corresponds with the onset of high levels of PCB. If the disappearance of the Caspian tern from Saginaw Bay in the mid 1960s corresponds with the onset of GLEMEDS at that location, then there is a close temporal relationship to the onset of high PCB levels. Chick-edema disease is difficult to diagnose because there is no specific lesion, but rather there is a suite of lesions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1875431 TI - Profound hypothermia (less than 10 degrees C) compared with deep hypothermia (15 degrees C) improves neurologic outcome in dogs after two hours' circulatory arrest induced to enable resuscitative surgery. AB - Deaths from uncontrollable hemorrhage might be prevented by arresting the circulation under protective hypothermia to allow resuscitative surgery to repair these injuries in a bloodless field. We have shown previously that in hemorrhagic shock, circulatory arrest of 60 minutes under deep hypothermia (tympanic membrane temperature, Ttm = 15 degrees C) was the maximum duration of arrest that allowed normal brain recovery. We hypothesize that profound cerebral hypothermia (Ttm less than 10 degrees C) could extend the duration of safe circulatory arrest. In pilot experiments, we found that the cardiopulmonary system did not tolerate arrest at a core (esophageal) temperature (Tes) of less than 10 degrees C. Twenty two dogs underwent 30-minute hemorrhagic shock (mean arterial pressure 40 mm Hg), rapid cooling by cardiopulmonary bypass (CPB), blood washout to a hematocrit of less than 10%, and circulatory arrest of 2 hours. In deep hypothermia group 1 (n = 10), Ttm was maintained at 15 degrees C during arrest. In profound hypothermia group 2 (n = 12), during cooling with CPB, the head was immersed in ice water, which decreased Ttm to 4 degrees-7 degrees C. The Tes was 10 degrees C in all dogs during arrest. Reperfusion and rewarming were by CPB for 2 hours. Controlled ventilation was to 24 hours, intensive care to 72 hours. In the 20 dogs that followed protocol, best neurologic deficit scores (0% = normal, 100% = brain death) at 24-72 hours were 23% +/- 19% in group 1 and 12% +/- 8% in group 2 (p = 0.15). Overall performance categories and histologic damage scores were significantly better in group 2 (p = 0.04 and p less than 0.001, respectively). We conclude that profound cerebral hypothermia with CPB plus ice water immersion of the head can extend the brain's tolerance of therapeutic circulatory arrest beyond that achieved with deep hypothermia. PMID- 1875432 TI - Experimental hemorrhage and blunt trauma do not increase circulating tumor necrosis factor. AB - Tumor necrosis factor (TNF) is a potent cytokine mediator of the shock states associated with sepsis and burn injury. This experimental study was done to determine whether circulating TNF plays a major role in the vasomotor collapse seen following experimental hemorrhage and blunt injury. Twenty anesthetized pigs were divided into two groups. Ten animals were bled 60% of their calculated blood volume in 15 minutes. Animals in Group IA (n = 5) had no treatment, and Group IB animals (n = 5) were given twice the shed volume as crystalloid 30 minutes after hemorrhage. The other animals, groups IIa and IIb (n = 5 each), were first subjected to a blunt injury to the thigh sufficient to cause a midshaft femur fracture, then bled and similarly treated. In both groups, mean arterial pressure (MAP), cardiac output (CO), and serum TNF activity by L929 bioassay were measured at 15-minute intervals for 120 minutes after hemorrhage or hemorrhage and blunt injury. An additional three animals were infused with 4 x 10(8)/kg heat-killed E. coli to validate the TNF assay. All bled animals sustained a fall in MAP and CO to a mean of 33% of baseline values, with or without fracture. Group IB and IIB animals responded to fluid resuscitation by restoration of MAP and CO to 85%-97% of the baseline values. Tumor necrosis factor was not detectable before injury and remained undetectable in all these animals during the 120 minutes of the experiment despite hemorrhage alone or combined hemorrhage and blunt trauma, with or without fluid resuscitation. The test animals receiving the E. coli responded with markedly elevated TNF levels, which peaked at 90 minutes after injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875433 TI - "Directed" emergency room thoracotomy: a prognostic prerequisite for survival. AB - The results of 163 patients (49 SWs, 85 GSWs, 29 blunt trauma) who had resuscitative thoracotomy in the emergency room (ERT) were reviewed to reassess the indications for the procedure. The Revised Trauma Score (RTS) of the patients ranged from 0 to 3 in 138, 4 to 8 in 21, and greater than 8 in four. No patient with blunt trauma survived. Sixteen patients [12 (24.5%) with stab wounds and 4 (4.7%) with gunshot wounds] were eventually discharged, an overall survival of 9.8%. Eight of the survivors were without vital signs on arrival at the emergency center and one of them had only signs of life at the scene. Survival was best when the site of penetration was thoracic (n = 84) and the ERT was "directed" at potential cardiac injury. Fifty-six of these patients (66.6%) did have cardiac wounds with tamponade and 12 of them survived (21.4%). Two of the remaining 28 patients, both with pulmonary injury, were salvaged. This was significantly (p less than 0.001) higher than in patients with head and neck (n = 4), abdominal (n = 19), or multiple site (n = 40) injury when the ERT was nondirected. Two of the five patients (40%) with extremity vascular injuries survived after ERT was successful in restoring a cardiac rhythm. These data suggest that in patients without vital signs, ERT "directed" at potential cardiac injury based on thoracic penetration is an important prognostic prerequisite for survival. Emergency room thoracotomy is not beneficial in blunt trauma and its role in penetrating abdominal injuries remains unproven. PMID- 1875434 TI - Bacterial translocation in trauma patients. AB - Sepsis and multiple system organ failure (MSOF) are major causes of morbidity and mortality in trauma patients. Bacterial translocation induced by hypotension, endotoxemia, or burns is a reproducible phenomenon in the laboratory. The incidence of bacterial translocation to mesenteric lymph nodes (MLNs) in 29 critically ill patients was evaluated to determine its relationship to subsequent sepsis and MSOF. Bacterial translocation was documented in 3 of 4 patients who underwent laparotomy for gastrointestinal (GI) disease. No trauma patient (25 patients), even at second exploration 3-5 days after injury, had a positive MLN culture. Five patients died; 4 trauma patients, one with GI disease. Forty percent of the trauma patients had major complications, predominantly pulmonary infections with gram-negative bacteria. However, infectious complications and outcome were not related to MLN culture results. The classical progression of bacteria from the gut to the bloodstream via the MLNs may require time and gut mucosal injury. The data suggest that bacterial translocation to the MLNs is not a common occurrence in acutely injured trauma patients. PMID- 1875435 TI - Severely injured geriatric patients return to independent living: a study of factors influencing function and independence. AB - Our previous work demonstrated that geriatric trauma patients (age greater than 65 years) consume disproportionate amounts of health care resources. In the past we hypothesized that late mortality is high, long-term outcome is poor, and return to independence is low in a severely injured geriatric population. Of 6,480 trauma admissions over 5 years, geriatric patients (n = 495) with blunt trauma injury (n = 421) and an ISS greater than 16 (n = 105) who survived until discharge (n = 61) underwent long-term follow-up (mean = 2.82 years). We surveyed 20 measures of functional ability; 10 measures of independence; availability and use of rehabilitation resources; employment history; alcohol use; support systems; and nursing home requirements. Of the 105 patients, 7 were subsequently lost to follow-up. Among the remaining 98, 44 (44.9%) died in hospital and 54 (55.1%) were discharged and interviewed. The mean age of the contacted patients was 72.6; their mean ISS was 23.3. Forty eight of 54 (88.9%) were alive at the time of interview, while 6/54 (11.1%) had died. Although only 8/48 patients regained their preinjury level of function, 32/48 (67%) returned to independent living. The 32 independent patients, those with "acceptable" outcome, were compared with an "unacceptable" outcome group composed of the 44 in-hospital deaths, the 6 late deaths, and the 16 dependent patients. Factors associated with poor outcome include a GCS score less than or equal to (p = 0.001), age greater than or equal to 75 (p = 0.004), shock upon admission (p = 0.014), presence of head injury (p = 0.03), and sepsis (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875436 TI - Total mesh wrapping for parenchymal liver injuries--a combined experimental and clinical study. AB - This study examined a mesh wrap technique that provides effective hepatic tamponade and clinical experience with the technique in 6 patients is reported. Technical feasibility and effectiveness were investigated in 8 miniature swine. The animals were divided into two groups: group A (n = 4), control animals; stellate liver lacerations without mesh wrap or other measures for hemostasis, and group B (n = 4); stellate liver laceration with synthetic absorbable mesh wrap applied for hepatic hemostasis. Except for mesh application, all variables were held constant for both groups. All animals in the control group died within 20 to 120 minutes (mean: 65 minutes). All animals in group B survived (p = 0.029). The livers were harvested for gross and microscopic examinations. No abscess, bile leak, or hematoma was noted. Clinically, total mesh wrapping was attempted in 6 patients with blunt exsanguinating liver injuries. The technique failed intraoperatively in two patients with juxtacaval lacerations and hepatic vein avulsion injuries. One patient with a bilobar gunshot wound died later of sepsis. In three patients with bursting injuries, the technique successfully controlled bleeding and resulted in long-term survival. In conclusion, the total hepatic mesh wrap (1) is geometrically, technically, and mechanically feasible, (2) was not associated with complications in this series, and (3) can effectively secure hemostasis following parenchymal liver injury. PMID- 1875437 TI - Child pedestrian injury: a population-based collision and injury severity profile. AB - Linked multiple data sources were analyzed to provide a population-based collision and injury severity profile among pedestrians under 20 years of age struck by a motor vehicle during 1986-1987 in Hartford, Connecticut. Data sources included police accident reports, medical examiner records, and hospital charts. There were 234 motor vehicle-pedestrian collisions reported to the police in the study period. Of these, 213 were Hartford residents resulting in an annual age specific pedestrian collision rate of 22.8 per 10,000 persons. A spot map of collision location reveals several well-defined geographic areas, which includes nearly half (45%) of the motor vehicle-pedestrian collisions. We reviewed 143 of 192 medical charts (75%) and 6 medical examiner records. The case fatality rate was 4.2% and the mean Injury Severity Score was 4.4. These findings will be useful for designing, implementing, and evaluating a targeted child pedestrian safety program. PMID- 1875438 TI - Cardiac output measurement in critical care patients: Thoracic Electrical Bioimpedance versus thermodilution. AB - Thoracic Electrical Bioimpedance (TEB) is a method for measuring cardiac performance which is noninvasive, continuous, has minimal technical requirements, and no patient risk. We used a commercially available TEB device to measure cardiac output in patients with thermodilution catheters in place. We compared the cardiac output measurements for the two modalities. We also compared the average hospital cost for initial cardiac assessment using the two techniques. The mean difference between the two cardiac output measurements was small (0.23 +/- 0.56) and not affected by the magnitude of the cardiac output readings. There was a strong correlation between COTD and COTEB (r = 0.91) and the regression slope was 0.91 with a Y intercept of 0.76. Cost analysis demonstrated that the use of TEB was approximately $600 less than thermodilution. Thoracic electrical bioimpedance measurement of cardiac output may offer a valuable alternative to the invasive measurement of the thermodilution catheter. PMID- 1875439 TI - EAST issues seminar: the education of the trauma surgeon in the 21st century. PMID- 1875440 TI - Defining the major trauma patient and trauma severity. AB - Criteria for defining the major trauma patient have been specified by physicians using Injury Patient Management Categories (PMCs), a computerized classification that can be used effectively with routinely collected discharge abstract data from non-trauma center hospitals as well as trauma centers. These criteria for major trauma not only include the more severe and complex single injuries, but also include criteria for identifying combinations of injuries that require tertiary level care. Major trauma patients identified as tertiary using PMCs are compared with existing and frequently used measures of injury severity such as AIS and ISS. Analyses suggest that the Injury PMCs identify major trauma patients accurately and more specifically than other indicators of severity that are commonly used. In addition, unlike other measures that are generally limited to registries, PMC tertiary patient criteria differentiate major trauma patients at both trauma centers and non-trauma centers without additional data collection. Using this method thus facilitates trauma systems evaluation and patient outcome assessment. PMID- 1875441 TI - A randomized trial of replacement antioxidant vitamin therapy for neutrophil locomotory dysfunction in blunt trauma. AB - Studies in patients with serious trauma indicate that the observed neutrophil (PMN) locomotory dysfunction is partly the result of auto-oxidation as shown by evidence of preactivation, diminished reducing capacity, and low serum and cellular ascorbic acid and alpha-tocopherol. To investigate whether replacement of the antioxidant vitamins ascorbic acid and alpha-tocopherol can improve the PMN locomotory defect, ascorbic acid, alpha-tocopherol, ascorbic acid and alpha tocopherol, or placebo was administered to a total of 46 victims of blunt trauma. PMN locomotion was quantitated using a micropore filter assay. Locomotion data were analyzed by repeated measures analysis with a split plot design and data for days 2-6 after injury were compared. Compared with placebo, the antioxidants improved PMN locomotion. The mean differences in distance migrated (treated minus placebo) were ascorbic acid and alpha-tocopherol = 11.3 +/- 3.0 microns (one tailed p = 0.001) (mean +/- SE); ascorbic acid = 4.7 +/- 3.4 microns (p = 0.19); and alpha-tocopherol = 3.3 +/- 2.9 microns (p = 0.27). Although both antioxidants given together produced the best results, a plot of the 95% confidence intervals indicates that ascorbic acid and alpha-tocopherol, either given alone, were also better than placebo. We conclude that antioxidant replacement therapy significantly improves the PMN locomotory abnormality in blunt trauma. PMID- 1875442 TI - Continuous arteriovenous rewarming: report of a new technique for treating hypothermia. AB - Survival is rare after major trauma if core temperature falls below 32 degrees C. Available rewarming methods are often ineffective. We utilized arterial and venous catheters to create a circulatory fistula through the heating mechanism of a modified commercially available counter-current fluid warmer to achieve simple, rapid extracorporeal rewarming. PMID- 1875443 TI - The autotransfusion effect of external leg counterpressure in simulated mild hypovolemia. AB - We examined the cardiovascular response of external leg counterpressure in healthy volunteers at 100 mm Hg compression pressure. To stimulate mild hypovolemia, measurements were made with the subjects in a 60 degrees head-up tilt position. Left ventricular end-diastolic volume (LVEDV) and cardiac output (CO) were calculated from two-dimensional echocardiography. Flow through the inferior vena cava (IVC) below the origin of the hepatic veins was determined by the Doppler ultrasound technique. The application of counterpressure significantly increased LVEDV, CO, and arterial blood pressure over that seen with tilting without the device. These responses were accompanied by a small but significant increase in IVC flow. We therefore concluded that external leg counterpressure transferred blood to the central circulation by compression of the venous capacitance vessels (an autotransfusion effect) in mild hypovolemia, but such an effect may not benefit patients in a hypovolemic shock state because of the small amount of translocated blood. PMID- 1875444 TI - Predictors of abdominal injury in children with pelvic fracture. AB - During a 48-month period, 2,248 children (aged less than 15 years) were consecutively admitted to a regional pediatric trauma center with blunt trauma (ICD-9-CM code greater than or equal to 800). Fifty-four children (2.4%) had injury to the pelvic circle, as diagnosed by radiographic examination; 13 of these children had concomitant abdominal or genitourinary (GU) injury. Contingency table analysis and stepwise logistic regression were used to determine the best predictors of abdominal injury. The mean age of the children was 8.6 years. Eighty-nine percent of the injuries were motor-vehicle related (59% pedestrian; 30% crash occupant). Nine children (17%) required transfusions of packed red blood cells; 9 children (17%) required surgery. There were 6 deaths in this group, a mortality rate of 11.1%. The most common fracture sites in the pelvis were the pubic rami (59%), ilium or pelvic rim (17%), and the sacrum (6%). Ten children (19%) had multiple pelvic fractures. Location of fracture was strongly associated with the probability of abdominal injury: 80% of children with multiple pelvic fractures had concomitant abdominal or GU injury, compared with 33% with fracture of the ilium or pelvic rim, and 6% with isolated pubic fractures (p less than 0.001). The variables that best predicted abdominal or GU injury using a backward-elimination, stepwise logistic model were the presence of multiple pelvic fractures (p less than 0.002) and unweighted Revised Trauma Score (p less than 0.05); age of child, systolic blood pressure, respiration rate, Glasgow Coma Scale score, and mechanism of injury were not predictive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875445 TI - Superselective embolization of superior gluteal artery pseudoaneurysms following intramuscular injection: case report. AB - Two bleeding superior gluteal artery pseudoaneurysms occurred in a patient with advanced malignant disease following an intramuscular injection. This was diagnosed by angiography and successfully managed by superselective embolization. This avoided further surgery and no additional complication from the pseudoaneurysm occurred up to the time of the patient's demise. PMID- 1875446 TI - An experimental study of lung lesions caused by extracellular enzyme of Streptomyces thermohygroscopicus. AB - Rabbits and rats were infected intratracheally with extracellular enzyme of Streptomyces thermohygroscopicus (H9-4) by only one exposure, and lesions of the lung developed including mononuclear macrophage infiltration as well as bronchitis and vasculitis. The obvious damages in type I pneumocytes, endothelial cells of capillaries and arterioles in the lung were observed by electron microscopy. Immunofluorescent histochemistry examination revealed exudation of plasma fibronectin which might play an important role during the process of lesion repairing in lung. The experiment also confirmed that extracellular enzyme of Streptomyces thermohygroscopicus might directly damage the lung tissue. These experimental data may serve as valuable reference for studying the etiology and pathogenesis of farmer's lung disease. PMID- 1875447 TI - Noninvasive diagnosis of latent pulmonary hypertension in COPD by exercise-load impedance rheopneumogram: a comparative study with right heart catheterization. AB - Impedance rheopneumogram (IRP) and right heart Swan-Ganz catheter examinations were simultaneously carried out in 63 patients. Two equations for calculating after-exercise-pulmonary-pressure (PAPm) were obtained by stepwise regression analysis: 1) PAPm (kPa) = -1.40-0.88.InHs+8.30.(B-F)+5.78.Q-B/B-Y (r = 0.730, IRP is measured at rest); 2) PAPm(kPa) = 6.46-5.04.Hs/square root of R-R +4.35.Q-B/B Y-19.34.(Q-C) (r = 0.648, IRP is measured after exercise). This is a new method for diagnosing latent pulmonary hypertension noninvasively. PMID- 1875448 TI - Effects of benzyltetrahydropalmatine on delayed after depolarization and triggered activity and on His-bundle electrogram and ECG in animal experiment. AB - Standard microelectrode techniques were used to study the effects of benzyltetrahydropalmatine (BTHP) on ouabain-induced delayed after depolarization (DAD) and triggered activity in isolated guinea papillary muscles. The results indicate that ouabain-induced DAD and triggered activity were abolished by BTHP 100 mumol/L. In anesthetized rabbit ECG heart rate was reduced in a dose dependent manner from control value of 288 +/- 14 to 261 +/- 14 (BTHP 5 mg/kg) and 226 +/- 36 bpm (BTHP 10 mg/kg). P-R interval was prolonged. In His-bundle electrogram, H-V interval and V duration were not affected, but A-H interval was prolonged from 41 +/- 3 to 45 +/- 5 ms. PMID- 1875449 TI - Effect of central RAS on one-kidney Grollman hypertension in rats and its mechanism. AB - The effect of central renin-angiotensin system (RAS) on one-kidney Grollman hypertension during the maintaining phase and its mechanism were investigated in rats. The arterial blood pressure (ABP) and the content of angiotensin II (A II) and norepinephrine (NE) in brain regions was measured respectively. 4 weeks after operation the ABP was elevated significantly, and it sustained at high level 8 weeks post-operatively. However, ABP in the control group underwent no significant changes at the same period. The A II and the NE content in the brain regions of the operated group were significantly higher than in those of the age matched control group. During the maintaining phase of hypertension captopril (150 micrograms/10 microliters) was injected into the lateral cerebroventricle at 0.5 h, 1.0 h and 1.5 h respectively, and ABP and content of A II and NE were determined at the corresponding time. The results showed that the above three parameters decreased consistently at 0.5 h and 1.0 h, and increased gradually at 1.5 h, suggesting that the central RAS might play an important role in the maintaining phase of one-kidney Grollman hypertension in rats. PMID- 1875450 TI - The effects of the combination of phentolamine and vasopressin on hepatic and systemic hemodynamics in cirrhotic portal hypertensive dog model. AB - The experimental study was aimed at elucidating the effects of phentolamine and vasopressin used separately or in combination on hepatic and systemic hemodynamics in cirrhotic portal hypertensive dogs. The results showed that either of the two drugs used separately could lead to reduction in portal venous pressure and could also influence systemic hemodynamics or lower hepatic blood flow. When phentolamine in combination with vasopressin was administered, no side effect could be found on hepatic and systemic hemodynamics, suggesting that the drugs used in combination could efficaciously decrease portal hypertension and counteract their respective side-effect. This combination therapy will be useful in treating bleeding from esophageal variceal rupture in cirrhotic patients with portal hypertension. PMID- 1875451 TI - Relationship of VLDL receptor and LPL in metabolism of VLDL by macrophage. AB - Macrophages were incubated with 125I-VLDL for 5 h in presence or absence of lipoprotein lipase (LPL) inhibitor, benzene boronic acid (BBA). Both the uptake and degradation of 125I-VLDL by macrophages were saturable, and the uptake and degradation curves were virtually identical. When macrophages were incubated with 125I-VLDL for 10 h in presence of BBA, the uptake and degradation of 125I-VLDL were still saturable. However, in absence of BBA, the uptake and degradation were no longer saturable. The results suggest that with macrophages incubated with VLDL for a shorter period, VLDL was taken up predominantly via receptor pathway, with a longer period of incubation, LPL played a striking role in uptake of VLDL. PMID- 1875452 TI - Skin-visceral divergent projection of cholecystokinin-containing dorsal root ganglion neurons: a tri-labelling study with fluorescent tracers and immunohistochemistry. AB - Skin-visceral divergent projections of cholecystokinin (CCK)-containing dorsal root ganglion neurons were studied by combined technique of fluorescent double labelling and immunohistochemistry. Fast blue (FB) and nuclear yellow (NY) were injected into the coeliac ganglion and the cutaneous branches of left 9th-11th intercostal nerves, respectively. Three kinds of neurons labelled with fluorescein were observed in T9-11 dorsal root ganglia: FB-labelled neurons with blue-fluorescent cytoplasm; NY-labelled neurons with yellow-fluorescent nucleus and double-labelled neurons with blue cytoplasm and yellow nucleus. The double labelled neurons were found to account for 2.8% of total labelled neurons. The sections containing neurons labelled with fluorescein were stained by CCK immunohistochemical procedure. Four kinds of neurons could be identified: NY neurons with CCK-immunoreactivity (NY+CCK); FB-neurons with CCK-immunoreactivity (FB+CCK); NY+FB neurons with CCK-immunoreactivity (NY+FB+CCK); and neurons only CCK-positive. NY+FB+CCK tri-labelled neurons accounted for approximately 11.5% of NY+FB double-labelled neurons, and for 0.4% of all CCK-positive neurons. The findings clearly indicated that the peripheral processes of some sensory dorsal root ganglion neurons divergently project to both skin and visceral structure and contain CCK. PMID- 1875453 TI - Simultaneous pancreaticoduodenal and renal transplantation in one diabetic patient with end-stage renal disease. AB - The diabetic patient with renal failure underwent simultaneous pancreaticoduodenal and renal transplantation. Duodeno-cystostomy was performed for the drainage of exocrine secretion. Immediately after grafting, the pancreatic and the renal graft regained normal function, and there was no operative complication whatever. The patient had functioning pancreatic graft and became insulin-independent for more than 3 months, although two transplanted kidneys were rejected. Immunosuppression consisted of cyclosporine A, azathioprine and prednisone. Our results suggest that hemorrheological parameters may serve as early indicators of acute rejection and be used to estimate the efficacy of anti-rejection and anti-coagulation therapy. PMID- 1875454 TI - Information medicine and its primary functions of exploitation of medical resources. AB - The aim of this paper is to continue the discussion on the defects of the structures of medical resources and their applicability at the present time, and then to design the qualitative networklike subsystem of the new research Quantitatively Medicine Simulating and Operating by Computer (QMSOC) and a five library model of the new knowledge-base of QMSOC. Finally, a set of results from the primary functions of exploitation of pancreas-glucagon-insulin information by QMSOC are presented. PMID- 1875455 TI - Effects of cigarette smoking, hypoxia and vasoactive mediators on the production of PGI2 and TXA2 in cultured pulmonary artery endothelial cells. AB - Effects of cigarette smoke extract (CSE) and some vasoactive mediators on the production of PGI2 and TXA2 in normoxic and hypoxic pulmonary artery endothelial cells (PAECs) in culture were studied. The production of PGI2 in PAECs was inhibited by hypoxia or verapamil, but promoted by angiotensin II (A II), noradrenaline (NE) or platelet activating factor (PAF), while that of TXA2 slightly increased except when treated with PAF. The effect of AII, NE, PAF and verapamil, however, was not influenced by hypoxia. CSE inhibited the production of PGI2 in normoxic PAECs but did not further reduce 6-keto-PGF1 alpha in hypoxic PAECs medium. The results suggest that a) the production of PGI2 during hypoxia might be stimulated by vasoactive mediators produced during hypoxia, not by hypoxia directly; b) the production and release of PGI2 were related to intracellular calcium; c) the augmented production of PGI2 might be one of the mechanisms in the pulmonary vasodilating role of PAF; and d) prostaglandin production might be associated with the alteration of hypoxic pulmonary vasoreactivity after cigarette smoking. PMID- 1875456 TI - [Effects of family medicine education on medical students' attitudes]. AB - Undergraduate education is considered to be one of the main contributory factors for the development of family medicine through increasing the number of medical graduates opting for a career in family practice. To evaluate the effects of family medicine education on student's attitudes, 140 fifth year medical students were asked in 1989 to fill in a questionnaire both before and after their curricula. The average age of the 123 students who completed the questionnaire on both occasions was 24.9 years; 106 were males; 17 were tuition free and 26 took additional family medicine clerkships. On aggregate, the students' disposition toward family medicine before their curricula appeared to be uncertain. Mean scores on the attitude scale did not significantly differ between socioeconomic subgroups before the curricula. After the curricula, students' attitudes were significantly altered, especially toward the future development of family medicine in Taiwan. However, their disposition toward family practice as a career changed the least. The degree of alteration in students' attitude toward family medicine before and after the curricula was related to the intensity of the course and to their socioeconomic backgrounds. PMID- 1875457 TI - Intramuscular-injection-associated gluteal fibrotic contracture and hepatitis B virus infection among school children. AB - A case control study was carried out to determine the exposure factors of gluteal fibrotic contracture (GFC). Sixty two school children were taken as the case group and were matched for sex, age and village of residence with 62 of their classmates constituting the control group. It was found that all 62 members of the case group had received intramuscular (IM) injections at some time prior to the onset of GFC, while only 57 of the control group had received IM injections. This difference is a statistically significant (p = 0.029). Injection sites on both buttocks were higher in the case group than among the controls. The odds ratio for the prevalence of hepatitis B virus infection (HBV) in the case group as compared to the control group was 3.0 (95% CI 1.1-7.8). A trend correlation was found between the annual frequency of IM injection, GFC and HBV infection. We concluded that IM injections played an important role in GFC and added to the risk of HBV infection, because they had been administered by improperly sterilized reusable syringes in an area where both GFC and HBV infections were prevalent and IM injection was common. PMID- 1875458 TI - Primary adenocarcinoma of the esophagus. AB - From Oct. 1982 to Sep. 1990, 450 cases of tissue proven carcinoma of the esophagus were treated at Taichung Veterans General Hospital, seven of these were primary adenocarcinoma of the esophagus, but only two had been diagnosed pre operatively (by endoscopy). Most primary lesions may have originated from the submucosal gland of esophagus. The pathological characteristics included submucosal tumor infiltration without dysplasia of epithelium around the tumor margin and absence of Barrentt's epithelium. Five of the seven patients received surgical resection and four patients showed negative lymph node metastasis. Three of the node negative patients are still alive 23, 29 and 58 months after the operation. Thus long term survival may be expected after surgical resection in node negative primary adenocarcinoma of the esophagus. PMID- 1875459 TI - [Diabetic foot infections: a preliminary report]. AB - Foot infection is a common cause of hospitalization for diabetic patients. Our study aimed to analyze patients' age, sex, the primary sites of infection, presenting features, outcome, bacteriologic studies and their clinical significance in diabetic foot infections. The age of our diabetic patients with foot infections ranged from 43 to 82 years, with a mean of 62.5 years; fifty-two of them were males and twenty-eight were females. The male to female ratio was 1.9:1, but there was no statistically significant difference between the sexes (p greater than 0.05). The commonest age group was the seventh decade of life (47.5%), followed by the sixth decade (32.5%). The commonest primary site of infection was the toes (53.8%), followed by foot area other than toe (25%) and the leg area was the least frequent (21.2%). Cellulitis combined with other foot lesions presented in 78.8% of these patients, foot ulcers in 75% of them, gangrenous change in 68%, necrotizing cellulitis or fasciitis in 16.3%, abscess formation in 12.5% and osteomyelitis in 7.5%. The legs were amputated in 53 patients (66.3%), usually below the knee (in 47.5%). We found that patients with a long history of DM had statistically significantly higher rate of amputation (p less than 0.01) than patients with only a brief history. Bacterial cultures from the infected foot lesions yielded numerous organisms in 58.8% of cases and a single organism in 31.1% of cases. Proteus mirabilis was the commonest organism isolated, followed by E. coli, Pseudomonas aeruginosa. The commonest month of the onset of diabetic foot infection was January, followed by February. PMID- 1875460 TI - Insulinoma: a case report. AB - Insulinoma is a rare disease, which frequently causes hypoglycemic symptoms and signs or even shock. However, other diseases that produce similar symptoms and signs should firstly be ruled out. We describe a 63 years old male veteran who suffered from repeated episodes of seizure and conscious disturbance upon fasting, on and off for 8 years. Serial examinations led to the suspicion that this might be a case of insulinoma; the suspicion was later confirmed by pathologic examination after the tumor had been excised, and his problems disappeared. After six years, a follow-up examination showed that his condition was still stable. PMID- 1875461 TI - Dilaceration of a central incisor with iatrogenic root perforation--a case report. AB - Dilacerated tooth is caused by disruption of the follicle of the developing tooth secondary to traumatic injury of its deciduous predecessor. This case presented a dilacerated permanent maxillary incisor which was perforated in root canal at buccal side by general practitioner and treated successfully by conservative endodontic therapy. PMID- 1875462 TI - [Acetabular roof reconstruction with femoral head bone-graft for severe acetabular deficiency in total hip replacement]. AB - From July 1984 to September 1989 at Taichung Veterans General Hospital, 14 patients (15 hips) received femoral head bone-grafting by modified Harris method as a part of their total hip replacement for acetabular bony deficiencies. They were followed up for an average of 31.7 months (range from 7 to 66 months). The clinical results were classified as excellent (58.3%) and good (41.7%) by Harris hip scoring system. All the grafts presented as "solid incorporation" with the pelvic wall and only one of the grafts was assessed to be "definite resorption" (volume reduction greater than 50%) by radiologic study. The "biologic viability" of these grafts were proved to be positive by scintigraphy in three-dimensional technique (SPECT). According to our limited experience and primary follow-up studies, we found that good clinical results depend on ideal positioning of the acetabular component in the true acetabulum and femoral head bone-grafting is an ideal procedure for the reconstruction of severe acetabular dysplasia in total hip arthroplasty. PMID- 1875463 TI - [Evaluation of urinary polyamines in patients with nasopharyngeal carcinoma]. AB - A new and simple enzymatic assay utilizing an acylpolyamine amidohydrolase and putrescine oxidase was adopted for measuring urinary polyamines (U-Pa). Serum carcinoembryonic antigen (S-CEA) was determined for comparison. The study population consisted of patients with pathologically proven nasopharyngeal carcinoma (NPC) who were referred to Kaohsiung Medical College Hospital. We found that polyamine levels were markedly elevated during radiotherapy but declined when the treatment was completed. Thus mean polyamines and the positive rate of polyamine elevation was higher in patients suffering from an active stage of the disease than in patients whose cancer had stabilized. However, the level of carcinoembryonic antigen was not elevated whilst undergoing radiotherapy. Therefore, routine measurement of polyamine levels may have a clinical utility in monitoring the disease state of the tumor. However, the low sensitivity of U-Pa test (22%) precludes its use as an effective screening method for this condition. Nevertheless, because of its simplicity, convenience and rapidity for monitoring NPC, U-Pa test should be considered a valuable tool in the clinical investigation of NPC patients. PMID- 1875464 TI - Clinical experience in threaded-in cup acetabuloplasty. AB - By utilizing torque and compression to gain purchase of the acetabular cup into the bony margin of the acetabulum, the concept of threaded-in acetabular implant is attractive. However, controversies about long term fixation have recently arisen. From July 1985 to June 1989, 37 cases (42 hips) were treated with Mecron hemispheric self-tapering threaded-in acetabular cup. With a minimum postoperative period of 2 years, 29 cases (32 hips) were followed up clinically and roentgenographically for an average of 39 months. Among these THRs, 15 operations (47%) were performed primarily and 17 operations (53%) were performed as revisional arthroplasty. Of the 15 primary THRs, 10 hips were operations for osteonecrosis of the femoral head. The success rate in the primary group was 87%, and 59% in the revisional group. In our experience, the Mecron threaded-in cup has been associated with a relatively high rate of failure. However, the high percentage of revisional surgeries and osteonecrotic cases in this study may be factors determining the poor results. PMID- 1875465 TI - [Combined CA-125 test and ultrasonography in the presurgical evaluation of ovarian mass]. AB - Clinicians are urgently searching for ways of differentiating a malignant from a benign ovarian mass. How to approach or what is the prognosis? Some have shown the CA-125 test combined with ultrasonography to be highly sensitive and specific, when compared to single parameter. We examined 238 patients who underwent laparotomy for adnexal mass. Of these 44 were found to suffer from malignant tumors and 194 from benign lesions. Before the operation, CA-125 level was measured; pelvic ultrasonography was performed on each patient and the sonographic data were evaluated on an echostructural scoring system. After a sophisticated computer assisted analysis, the results of the combined tests were CA-125 greater than or equal to 65 U/ml or US score greater than or equal to 8 with a sensitivity of 77.3%, a specificity of 81.4% and a diagnostic accuracy of 80.7%. Therefore we confirm that CA-125 may be considered as a useful adjunct to sonography in the differential diagnosis of adnexal mass. PMID- 1875466 TI - Renal oncocytoma: report of two cases and review of literature. AB - Renal oncocytoma was previously reported as a benign tumor arising from proximal tubular epithelial cells, but malignant potential with local invasion and distant metastasis has been emphasized in recent literature. It is difficult to differentiate it from renal cell carcinoma, but four typical angiographical signs may give suggestive evidence of the tumor. Radical nephrectomy with lymphadenectomy may be the choice of treatment, except in solitary kidney, bilateral tumors, or contralateral renal cell carcinoma. We report two female patients who were found incidentally to have renal tumors during a survey of right upper quadrant pain. Typical angiographic signs were found incidentally to have renal tumors during a survey of right upper quadrant pain. Typical angiographic signs were found in one patient, and atypical signs in the other. Three and eight years after radical nephrectomy with para-aortic lymphadenectomy, there has been no evidence of local recurrence or distant metastasis. PMID- 1875467 TI - Primary retroperitoneal sarcomas--a report of 16 cases. AB - From November 1982 to August 1990, 16 patients with primary retroperitoneal sarcoma were treated in our hospital. The most frequent types of tumor were liposarcoma (6), malignant fibrous histiocytoma (3). The commonest clinical findings were palpable abdominal mass (14/16). In management of these patients; nine patients underwent complete resection of the tumor; three patients underwent partial resection of the tumor and four patients underwent biopsy only. The histology of tumor appeared to have prognostic significance. Patients suffering from liposarcoma (3/5) and malignant fibrous histiocytoma (1/2) survived the longest. With a mean follow up of 25.0 months, the three year overall survival rate of complete resection group was 50 per cent. No patients with partial resection and biopsy only group survive three years and the total three-years overall survival rate was 29%. The mean survival for patients after adjuvant chemotherapy and/or radiotherapy was similar to that after a radical operation alone. The prognosis of primary retroperitoneal sarcoma is grave and complete resection of the tumor as initial treatment seems to provide the only chance of cure for these patients. PMID- 1875468 TI - The posterior glottis. AB - The posterior glottis is an area of the larynx previously referred to by the terms 'posterior commissure' and 'interarytenoid'; these are poorly defined and a new definition of this unique area of the larynx is provided. Within the text is a series of experiments performed on nearly 300 larynges. The posterior glottis was examined in relation to the following: the embryology, the epithelium, mathematical dimensions, gross anatomy, microanatomical structures, submucosal spaces and the spread of carcinoma related to this area. Various significant findings were made. There exists a pharyngoglottic duct which divides the embryonic larynx into anterior (membranous) and posterior (cartilaginous) parts. The epithelium of the posterior glottis in neonates and non-smokers is respiratory in nature and the notion of a laryngeal respiratory function is reinforced by a mathematical analysis of the cross sectional areas of the larynx during inspiration. The presence of a posterior cricoarytenoid ligament which stabilizes the arytenoid is confirmed. The spread of carcinoma to the posterior glottis from the different primary laryngeal and pyriform fossa sites shows differing modes of invasion but in particular a direct extension and connection with the subglottis. The most significant conclusion from these studies is that the posterior glottis is so intimately related to the subglottis that it must be considered as part of the subglottis. The acceptance of this fact, however, requires a new definition of the larynx from that given by the American Joint Committee on Cancer Staging and that of U.I.C.C. The posterior glottis considered as part of the subglottis requires a review of our present understanding of the structure and function of the larynx and in particular the spread of cancer posteriorly. PMID- 1875469 TI - The urological application of electrosurgery. PMID- 1875470 TI - Iohexol clearance for the determination of glomerular filtration rate in clinical practice: evidence for a new gold standard. AB - X-ray fluorescence analysis provides a simple method of measuring glomerular filtration rate from the clearance of ordinary unlabeled radiographic contrast media. To measure the accuracy of iohexol clearance using a clinically simple 2 sample single injection technique, a comparison was made in 30 patients with classical continuous infusion techniques for plasma (y = 1.03x - 0.015, r = 0.981) and renal (y = 0.950x + 7.26, r = 0.964) iohexol clearance. A comparison was made with classical inulin clearance. The renal clearance of iohexol and inulin was virtually identical (y = 0.998x + 2.31, r = 0.986). Single injection iohexol clearance agreed closely with the renal inulin clearance (y = 0.947x + 4.92, r = 0.983) as did clearance based on a single 3-hour sample (y = 0.875x + 12.63, r = 0.962). Iohexol clearance using x-ray fluorescence is a simple, rapid and accurate alternative to inulin clearance for clinical and research purposes. PMID- 1875471 TI - Microscopic hematuria: advances in identification of glomerular dysmorphic erythrocytes. AB - The high diagnostic sensitivity and specificity of microscopically visible, typically glomerular dysmorphic erythrocytes for identification of the cause of glomerular bleeding have been recognized worldwide. Although glomerular dysmorphic erythrocytes are simple to detect on phase contrast microscopy, immediate microscopic diagnosis still is indispensable, since a change in the morphology of the erythrocytes with restriction of the diagnostic relevance is anticipated because of the high autolytic potency of the urine. It may be postulated that this need for immediate diagnosis has led to the method being neglected owing to the high work load at hospitals and physician offices. Moreover, a physician who does not perform microscopic investigations or who lacks experience with the method will not be able to use this diagnostic technique, since it appeared to be impossible to transport urine samples by mail. In the context of a study comprising 30 patients, of whom 10 had histologically confirmed glomerulonephritis, we have shown that glomerular dysmorphic erythrocytes have a manifest form stability for at least 3 days. The preservative used was thimerosal. Also, the urine can be investigated independent of time even after alcoholic Papanicolaou staining without an alteration of erythrocyte morphology. The practicality of the form stability of glomerular erythrocytes can be exploited in everyday medical routine. There are well founded prospects that the rate of early diagnosis of glomerulonephritis will increase. PMID- 1875472 TI - The nutcracker syndrome: new aspects of pathophysiology, diagnosis and treatment. AB - Magnetic resonance imaging (MRI) was used to study vascular anatomy in 3 patients with the nutcracker syndrome and in 10 healthy volunteers. From these studies an abnormal branching of the superior mesenteric artery from the aorta was identified as being the cause of the nutcracker syndrome. Consequently, surgical transposition of the left renal vein to achieve an unobstructed renal venous backflow was performed successfully in 2 patients, while 1 underwent nephrectomy. In 1 patient adjuvant ureteral instrumentation became necessary to aid occlusion of persisting shunts between peripelvic venous varicosities and the urinary tract. Awareness of the pathophysiology of the nutcracker syndrome ensures an early diagnosis, which should be confirmed by a combination of diagnostic procedures, including MRI. PMID- 1875473 TI - Fine needle cytodiagnosis of renal tuberculosis. AB - A total of 8 patients in whom renal tuberculosis was suspected on clinical or radiological grounds but in whom confirmation could not be achieved by urine culture underwent renal fine needle aspiration. Immediate cytodiagnosis was accomplished in 7 of 8 patients by the finding of Langhans' giant histiocytes, epithelioid histiocytes and necrotic debris. Later confirmation was obtained in all 8 cases by radiometric culture of aspiration material or saline rinses of the fine needles. This experience introduces fine needle aspiration cytology as a diagnostic modality in renal tuberculosis. PMID- 1875474 TI - Cytogenetic abnormalities associated with renal cell carcinoma. AB - Cytogenetic analysis was performed on 23 renal cell carcinomas (21 sporadic and 2 associated with von Hippel-Lindau's disease). Clonal chromosomal abnormalities were found in 19 of 21 of the sporadic tumors. The most frequent abnormalities were a loss or rearrangement of material in 3p (11 of 21 cases) or an extra chromosome 7 (7 of 21 cases). Correlation between specific chromosomal abnormalities and clinical presentation was absent with the exception of trisomy 7 and -Y, which occurred only in patients more than 60 years old. An increasing number of cytogenetic abnormalities were associated with a greater likelihood of renal vein and/or capsule involvement. Both patients with von Hippel-Lindau's disease had tumors with a normal karyotype. PMID- 1875475 TI - Flow cytometric deoxyribonucleic acid analysis in stage I renal cell carcinoma. AB - Tumor deoxyribonucleic acid (DNA) content was analyzed by flow cytometry in 60 consecutive patients with stage I renal cell carcinoma. Of 59 evaluable tumors 27 (46%) were homogeneously diploid, 1 (2%) was tetraploid and 31 (52%) were aneuploid. Of the 32 nondiploid tumors 25 were heterogeneous concerning ploidy. One of the 27 patients with diploid tumors had metastases compared to 5 of the 32 patients with nondiploid tumors (not significant). There was a significant difference in survival between patients with diploid and nondiploid tumors (p = 0.043). Neither nuclear grade, tumor cell type nor tumor size correlated with survival. Analysis of DNA content seems to predict survival significantly for patients with stage I renal cell carcinoma. PMID- 1875476 TI - The management of transitional cell carcinoma in solitary renal units. AB - Ten patients with urothelial malignancies involving a solitary functioning renal unit were treated at our center for an average of 24 months or until death. These patients were all managed by parenchyma-sparing methods, including percutaneous as well as ureteroscopic tumor resection. Of our patients 9 have received adjunctive chemotherapy in the form of bacillus Calmette-Guerin instillations. At the time of this report 5 of our patients were alive without evidence of disease, 4 were alive with evidence of either residual or recurrent neoplasia and 1 was dead of disease 5 years after original presentation. Patients with higher grade tumors or carcinoma in situ did less well than patients with low grade disease. We present an analysis of our experience with this complex patient population and discuss the implications of these data within the context of a growing literature on the topic of upper tract urothelial malignancy. PMID- 1875478 TI - Extracorporeal shock wave lithotripsy: an outpatient procedure. AB - At many centers circumstances have dictated that extracorporeal shock wave lithotripsy (ESWL*) be performed on an outpatient (that is same-day surgery or 1 day stay) basis. At our center, Louisiana Lithotripter, Inc., which is a privately owned ESWL unit located at Tulane University Hospital, we have had the opportunity to treat patients in the inpatient and outpatient setting since inception. Since our first ESWL treatment on December 18, 1985 we have treated more than 2,500 patients. Additionally, our unit was named an American Urological Association Training Center in October 1986, resulting in more than 200 urologist, nurse and technician trainee visits. The first 1,779 cases through December 31, 1988 have been thoroughly reviewed. The rate of outpatient ESWL has increased from 22% of the first 100 cases to more than 90% of the last 100. The cumulative over-all rate reached 70%. Currently, more than 95% of our cases are planned as same-day procedures. Safe and effective outpatient ESWL is able to be performed with first generation technology, paving the way for appropriate clinical application to newer technological modalities. PMID- 1875477 TI - Planned delayed nephrectomy after ethanol embolization of renal carcinoma. AB - Planned delayed nephrectomy after preoperative ethanol infarction was done in 6 patients with renal carcinoma. Three patients had intracaval extension of tumor, 2 had renal vein but no vena caval extension and 1 had no renal vein or vena caval involvement. Nephrectomy was delayed 22 to 44 days after embolization. In the patients with inferior vena caval extension shrinkage of tumor thrombus after embolization allowed for easier surgical resection. Furthermore, delay of nephrectomy after preoperative infarction was of value in improving the clinical status of high risk patients. PMID- 1875479 TI - Analgesia in anesthesia-free extracorporeal shock wave lithotripsy: a standardized protocol. AB - We treated 101 patients at our stone facility with the Dornier HM3 lithotriptor modified with the anesthesia-free design upgrade. A protocol designed by our anesthesiologists consisting of intravenous and intramuscular injections for sedation was used without any general or regional anesthesia required. Pre medication with intramuscular meperidine and promethazine, and oral diazepam was sufficient sedation in 43 patients, while 37 required additional intravenous meperidine and/or midazolam during the procedure, 16 were treated with intraprocedural medication alone and 5 required no medication at all. Care before, during and after the procedure was rendered by the urology staff for patients in American Society of Anesthesiologists risk category I or II. Treatment was successfully completed in all patients without complications. We compared this group to the 99 patients treated consecutively before the modification. Voltage used, number of shocks and stone burden were comparable in the 2 groups but average treatment time was prolonged with the upgraded equipment (39.2 versus 27.1 minutes) to a significant degree (p less than 0.001). PMID- 1875480 TI - Renal calculi in lower pole calices: what is the best method of treatment? AB - Percutaneous nephrolithotomy and extracorporeal shock wave lithotripsy (ESWL*) can be used in the treatment of lower pole caliceal calculi. In a retrospective analysis these 2 therapies were compared for treatment of solitary lower pole caliceal calculi to evaluate morbidity. During a 2-year period 23 patients treated with percutaneous nephrolithotomy and 24 who underwent ESWL with the Siemens Lithostar were analyzed in regard to the success rate, effectiveness quotient, complication rate, length of hospitalization and disability period. Followup consisted of ultrasound and/or a plain film of the kidneys, ureters and bladder 1 day and 1 to 3 months postoperatively. A nephrotomogram was included in the ESWL group. Complete removal of all stone fragments was achieved in 93.6% of the patients treated percutaneously without retreatment. In the ESWL group the success rate was 79.2% with a 41.6% retreatment rate. On the other hand, the ESWL group had a shorter hospitalization and an earlier return to normal physical activities. Among the patients who underwent a percutaneous operation 13% had complications compared to 4.1% in the ESWL group. The recurrence rate was higher in the former group (13% within a median of 18 months, compared to 8.3% within a median of 11 months in the ESWL group). The mean stone diameter was 1.42 cm. in the percutaneous group and 1.22 cm. in the ESWL group. Stone composition was similar in both groups. Since ESWL is an effective noninvasive procedure without the need for routine anesthesia and hospitalization, and with prompt return of the patient to a normal life it must be considered the method of choice for lower caliceal stones less than 2 cm. in diameter. However, percutaneous nephrolithotomy will continue to have a primary role in the management of larger stones. PMID- 1875481 TI - Extracorporeal shock wave lithotripsy for struvite renal calculi: prospective study with extended followup. AB - To clarify the significance of retained stone particles after extracorporeal shock wave lithotripsy (ESWL) for struvite renal calculi we followed 22 otherwise healthy women for 16 to 52 months (mean 39 months). Each patient had persistent Proteus mirabilis bacteriuria before ESWL and received a standardized regimen of antimicrobial therapy in the perioperative period only. Of the 22 patients 19 (86%) were cured of the persistent bacteriuria. Of these 19 patients 16 had retained stone particles at the beginning of surveillance and 10 had retained particles at last followup. None of the particles produced symptoms or enlarged. However, 1 of the patients who was rendered stone-free had a P. mirabilis reinfection at 20 months and a new stone developed. Of the 22 patients 3 (14%) had continued persistent P. mirabilis bacteriuria after ESWL. Two patients were subsequently cured of the infection with antibiotics alone (1), and with antibiotics and extraction of a new ureteral stone (1). The remaining patient had expansion of retained stone particles after 51 months of surveillance. We conclude that a stone-free kidney is an unrealistic objective of ESWL monotherapy for struvite renal calculi. However, the treatment usually will eradicate the accompanying persistent bacteriuria and sterile stone particles will not enlarge during the first 2 to 4 years after treatment. PMID- 1875482 TI - Bacteremia during extracorporeal shock wave lithotripsy of renal calculi. AB - An increasing incidence of bacterial endocarditis has been observed since the beginning of the last decade. An explanation for this fact is the expansion of diagnostic and therapeutic procedures in diverse medical disciplines. In a clinical study performed on 49 consecutive patients undergoing extracorporeal shock wave lithotripsy a 14.3% rate of bacteremia was detected during treatment. The bacterial spectrum consisted of gram-positive cocci, gram-negative cocci, Bacteroides capillosus and Proteus mirabilis. In principle, these results do not call for an antibiotic prophylaxis. Nevertheless, according to the recommendations of the American Heart Association and the Deutsche Gesellschaft fur Herz- und Kreislaufforschung, patients with a cardiac risk predisposing to bacterial endocarditis must receive perioperative antibiotic prophylaxis. PMID- 1875483 TI - Treatment of ureteral calculi with extracorporeal shock wave lithotripsy using the Lithostar device. AB - Shock wave requirements for fragmentation and the ultimate outcome after extracorporeal shock wave lithotripsy (ESWL) with the Lithostar device were analyzed in 107 renal units with solitary ureteral calculi. In situ treatment was done in 54 stones without prior manipulation and in 15 after failure of endoscopic manipulation. A total of 25 ureteral calculi was treated after bypass with a ureteral catheter or stent and 13 after push back to the pelvicaliceal system. Shock wave requirement for fragmentation was significantly higher for calculi of 101 to 400 mm. X mm. when compared with the requirement for smaller calculi. Shock wave requirement was also significantly higher for patients with similar sized stones treated in the prone compared to the supine position. The average number of shock waves required for disintegration was not significantly different among in situ or any of the manipulation categories of similar sized stone populations. Over-all satisfactory clearance was achieved in 77.5% of the treated ureteral calculi. Clearance status was unaffected by size up to 400 mm. X mm. and the position of the patient during treatment (prone or supine). Clearance of ureteral stones treated in situ without prior manipulation (76.5%) was numerically inferior, although statistically insignificant, to that for successfully manipulated calculi (bypassed 88% and pushed back 92.3%) but it was significantly better than the outcome obtained after failed manipulation (46.2%). ESWL with the Lithostar device is a successful mode of treatment within the entire ureteral length, and a vigorous attempt at push back before lithotripsy is unnecessary. PMID- 1875484 TI - Balloon dilation of the distal ureter to 24F: an effective method for ureteroscopic stone retrieval. AB - Early in our ureteroscopic experience, in an effort to facilitate retrieval of ureteral calculi with the 11.5F and 12.5F rigid ureteroscopes, the distal ureter was routinely balloon dilated to 24F. Among 131 ureteroscopic procedures all consecutive 108 distal ureteral calculi were successfully removed. However, only 65% of 23 upper ureteral calculi were extracted. A followup excretory urogram (6 weeks or later) in 86 patients revealed no distal ureteral strictures. A followup cystogram in 30 patients showed low grade vesicoureteral reflux in 20% of the patients and none of these individuals was symptomatic. As such, balloon dilation of the distal ureter to 24F appears to be well tolerated. Presently, given the advent of smaller ureteroscopes and lithotriptor probes, such extensive ureteral dilation is necessary only in a minority of patients with distal ureteral calculi. In these few patients with calculi resistant to lithotripsy balloon dilation of the ureter to 24F may allow for successful, safe stone extraction, thereby precluding open ureterolithotomy. PMID- 1875485 TI - Conversion of the electrohydraulic electrode to an electromechanical stone impactor: basic studies and a case report. AB - A 3.3F electrohydraulic electrode (Wolf 2137.23) has been confined within a spring with a metal end cap, irrigated with water and covered with a 0.003-inch metal sheath (outside diameter 5F). The electrohydraulic lithotripsy discharge (Wolf Generator 2137.50) at E1 causes the metal cap to extend 3 mm. at 1,500 cm. per second and creates an impact pressure of 600 to 800 bar. Stone fragmentation efficiency of the electromechanical impactor was equivalent to unshielded electrohydraulic lithotripsy (gallstone 2.83 mg. per pulse, struvite/apatite 1.41 mg. per pulse, cystine 0.41 mg. per pulse, uric acid 1.48 mg. per pulse and 100% calcium oxalate monohydrate 0.10 mg. per pulse). Studies of the discharge of the electromechanical impactor within the pig ureter showed that minimal ureteral submucosal edema and hemorrhage occurred at 300 shocks discharged at a single point, and disruption of the mucosa and partial injury to the muscle layer occurred after 600 shocks given at the site of a pinched pig ureter. Pushing the electromechanical impactor perpendicular to the wall of the pig bladder will create a mechanical perforation within 35 shocks (electrohydraulic lithotripsy within 2 shocks). One patient had excellent fragmentation of a lower ureteral mixed monohydrate and dihydrate stone under direct vision performed with the electromechanical impactor passed via a 9.5F ureteroscope. There was no evidence of mucosal injury with 500 shocks. The electromechanical impactor has been developed to provide a safe and inexpensive method of ureteral stone fragmentation or disimpaction. These studies were performed to establish limits of safety that may allow use of the electromechanical impactor for stone fragmentation in the ureter without the need for ureteroscopy. PMID- 1875486 TI - Early clinical experience with the transverse colon-gastric tube continent urinary reservoir. AB - The clinical results of the first 4 patients undergoing reconstruction with the transverse colon-gastric tube urinary reservoir are presented. All patients had a minimum 1-year follow-up. All 4 patients are continent with stable or improved renal function. Two patients required reoperation. Indications as well as possible modifications of this procedure are discussed. PMID- 1875487 TI - Continent diversion with an appendix conduit and an ileocecal bladder. AB - Since March 1989, 23 patients have undergone continent urinary diversion with an ileocecal bladder and a reimplanted appendix conduit. In 21 patients this procedure was combined with a radical cystectomy. Of the patients 7 required an endoscopic procedure before satisfactory self-catheterization could be established. This problem was more common early in the series. The continence mechanism is extremely simple and rapid to construct. Continence rates have been most satisfactory, with only 2 patients having secondary incontinence. PMID- 1875488 TI - Lower urinary tract reconstruction following cystectomy: experience and results in 126 patients using the Kock ileal reservoir with bilateral ureteroileal urethrostomy. AB - Between May 1986 and February 1990, 126 consecutive men underwent lower urinary tract reconstruction by means of bilateral ureteroileal urethrostomy using a Kock ileal reservoir. The early complication rate was 11.1%. Late complications requiring rehospitalization or reoperation have been surprisingly few: 1 for prolapse of the afferent antirefluxing nipple valve, 1 for calculi and 4 for artificial urinary sphincter placement due to unsatisfactory continence. Good continence has been achieved in 94% of the patients during the day and in 84% at night. Tumor recurred in the pelvis in 5 patients, with 4 requiring cutaneous urinary diversion. All patients had progression or died of metastatic disease. Our experience has yielded extraordinary results in terms of patient acceptance with few late complications or need for reoperation. PMID- 1875489 TI - Early repair of iatrogenic injury to the ureter or bladder after gynecological surgery. AB - Contrary to the traditional doctrine of delayed intervention in post-hysterectomy injuries of the ureter or bladder, the policy at our department has been to operate as soon as possible after the diagnosis is made. Of 68 patients (25 with vesicovaginal fistulas and 43 with ureteral injuries) early intervention was possible in 40 (59%). Primary healing was obtained in all patients. These results suggest that there is no disadvantage in early repair. PMID- 1875490 TI - Bacillus Calmette-Guerin and interleukin-2 for treatment of superficial bladder cancer. AB - A total of 22 patients with bladder cancer received bacillus Calmette-Guerin (BCG) and interleukin-2. Significant bladder tumor remissions were noted in 15 of 17 patients (88%). Of 5 patients with carcinoma in situ 1 was noncompliant and he died of carcinoma in situ. The other 4 patients are in remission. BCG alone was instilled in 22 additional patients with superficial bladder cancer. The remission rates were encouraging. Of the 22 patients 13 (59%) had remission of the bladder tumor. A half dose of BCG (60 mg.) is adequate when given weekly for 6 weeks. Maintenance therapy is important as noted in both of our clinical arms. BCG and interleukin-2 therapy results in a higher remission rate. PMID- 1875491 TI - Single potential analysis of cavernous electrical activity in impotent patients: a possible diagnostic method for autonomic cavernous dysfunction and cavernous smooth muscle degeneration. AB - Cavernous electrical activity was recorded in 214 patients with erectile dysfunction and in 39 normal patients. In 34 of the 39 normal patients potentials of a uniform shape were recorded during flaccidity. At cutoff frequencies of 0.5 to 500 Hz. the duration was 8 to 18 seconds (mean 12.8 +/- 2.8, seconds, standard deviation), the amplitude was 250 to 750 microv. (mean 444 +/- 109 microv.) and the polyphasity was 8 to 22 (mean 13.8 +/- 3.3). With increasing tumescence and rigidity during audiovisual sexual stimulation, high frequency potentials of low amplitude and short duration were found in the normal patients. In impotent patients with an upper motor neuron or peripheral lesion specific types of potentials were observed. In 11 of 14 impotent patients with insulin-dependent diabetes for more than 20 years and with clinical findings of cavernous myopathy the potentials showed low amplitude, irregular shape and slow depolarizations. Abnormal findings of cavernous electrical activity were recorded in 51.6% of the consecutive impotent patients. Our clinical study suggests that single potential analysis of cavernous electrical activity may be useful in the diagnosis of cavernous autonomic neuropathy and cavernous smooth muscle myopathy. PMID- 1875492 TI - Penile sensory disorders in erectile dysfunction: results of a comprehensive neuro-urophysiological diagnostic evaluation in 123 patients. AB - A total of 123 patients with complaints of erectile dysfunction and no clinically overt neurological disease underwent a comprehensive neuro-urophysiological diagnostic evaluation. The results were compared with those obtained in 50 healthy volunteers. Data gathered consisted of somatosensory evoked potentials from the posterior tibial nerve (tibial evoked potential) and from the dorsal penile nerve (pudendal evoked potential). Also, 2 sacral reflex latencies were measured (bulbocavernosus reflex and urethro-anal reflex). A total of 58 patients (47%) had at least 1 abnormal neuro-urophysiological measurement. Neuro urophysiological abnormalities were found more frequently in older patients. The tibial evoked potential was abnormal in 30 patients (24%), pudendal evoked potential in 21 (17%), bulbocavernosus reflex in 26 (21%) and urethro-anal reflex in 32 (26%). It was concluded that somatosensory disturbances constitute an important part of neuro-urophysiological abnormalities. Our results suggest a relationship between erectile dysfunction and subclinical, age-related (penile) sensory disorders. Our study corroborates the importance of penile sensibility for erectile (patho)physiology as suggested by others and supports the concept of sensory deficit impotence as an important cause of erectile dysfunction. PMID- 1875493 TI - Controlled trial of infusion cavernosometry in impotent and potent men. AB - Infusion cavernosometry often is performed to diagnose venous leak impotence. However, normal values have seldom been established in proved potent men. We performed a prospective study of infusion cavernosometry on nocturnal penile tumescence confirmed potent male volunteers and impotent men. Of 20 potent male controls 19 had resistance values of greater than 5 (mm. Hg.minute)/ml. Of 38 impotent men 20 (53%) had resistance values of less than 5 (mm.Hg. minute)/ml. There was considerable overlap between resistance values and infusion rates in potent and impotent men. Impotent men with resistances of greater than 5 (mm.Hg.minute)/ml. more often had normal nocturnal penile tumescence results than men with lower resistance values. Venous leakage is a significant cause of impotence. PMID- 1875494 TI - Pharmacological erection program using prostaglandin E1. AB - A total of 72 impotent patients entered into a pharmacological erection program using prostaglandin E1. Of the men 35 (49%) used prostaglandin E1 on a regular basis, while 37 (51%) failed to continue in the program beyond the in-office dose titration period. In patients who continue to use prostaglandin E1 the median duration of drug use is 7 months, with a range of 2 to 28 months. There have been no instances of cavernous fibrosis, systemic reaction or chemical priapism (erection present longer than 4 hours) in any patient. Only 8 men (11%) were unable to achieve an adequate erection with prostaglandin E1 injections. The most common adverse effect of prostaglandin E1 was penile pain after injection. The incidence of severe pain leading to drug discontinuation was 17% (12 of 72 patients) while mild to moderate pain occurred in 22% (16 of 72). Over-all, intracavernous prostaglandin E1 injections appear to be a safe, effective treatment for impotence in most men. PMID- 1875495 TI - Effect of meal on the physiological and physicochemical actions of potassium citrate. AB - The effect of meals on the physiological and physicochemical actions of potassium citrate was examined in 8 patients with nephrolithiasis maintained on a constant metabolic dietary regimen. Potassium citrate (20 mEq. 3 times per day), whether given with food or on an empty stomach, significantly increased urinary pH, citrate and potassium, and decreased urinary calcium and ammonium. Moreover, potassium citrate decreased urinary saturation of calcium oxalate and uric acid, although it slightly increased that of brushite. However, there was no significant difference in these measures when the drug was given with meals from the time when it was given on an empty stomach. Thus, the effect of potassium citrate on urinary risk factors is unaffected by food. PMID- 1875496 TI - Urinary excretion of Tamm-Horsfall protein in elderly women. AB - The incidence of urinary tract infection is higher in the geriatric population than in younger adults despite the exclusion of patients with known risk factors. Tamm-Horsfall protein, a renal glycoprotein excreted in urine, may constitute a natural defense mechanism against ascending urinary tract infection by binding mannose-sensitive fimbriated microorganisms. We hypothesized that the quantity of Tamm-Horsfall protein excreted is decreased in the elderly. Native aggregated Tamm-Horsfall protein was measured in urine samples from 24 young women (group 1, mean age 33 years) and 47 female nursing home patients (group 2, mean age 84 years) using enzyme-linked immunosorbent assay techniques. Another 16 elderly women (group 3, mean age 85 years) had active urinary tract infection. The aggregated Tamm-Horsfall protein was then disaggregated by dilution and quantified. Significant differences in mean urinary disaggregated Tamm-Horsfall protein concentrations were found between groups 1 (64.22 mg./l.) and 2 (35.07 mg./l.), and between groups 1 and 3 (34.71 mg./l.), respectively. In contrast, mean aggregated Tamm-Horsfall protein levels were significantly higher in group 2 (1.56 mg./l.) than in group 1 (0.92 mg./l.) or group 3 (0.97 mg./l.). Our studies show that urinary disaggregated Tamm-Horsfall protein concentration is decreased in the elderly, and that aggregated Tamm-Horsfall protein is increased compared to younger adults. The aggregated Tamm-Horsfall protein concentration is decreased in the elderly during episodes of urinary tract infection. PMID- 1875497 TI - Clinical application of video image flexible ureteronephroscope for diagnosis of upper urinary tract disorders. AB - Ureteroscopy has become the diagnostic and therapeutic procedure of choice for many conditions of the upper urinary tract. Technology is progressing rapidly in endourology, facilitating both goals. As reported previously, we developed a 2F video image flexible ureteronephroscope. This instrument is the smallest caliber of all ureteronephroscopes available to date. Because of the small diameter the device can be inserted into the ureter cystoscopically in a manner similar to catheter insertion. The procedure is done with the patient under local anesthesia. We performed ureteronephroscopic procedures on 79 patients using mainly a 6F passively deflecting flexible ureteronephroscope, which consists of the aforementioned 2F video image flexible ureteronephroscope and a 3F working channel. The area to be viewed was accessed successfully in 41 of 43 patients (95%). Over-all, diagnostic maneuvers were successful in 64 of 79 patients (87%). We suggest that the 2F and 6F flexible ureteronephroscopes would be indicated when conclusive diagnosis for upper urinary disease is not obtained by other means. PMID- 1875498 TI - Percutaneous suprapubic cystostomy using a modified urethral sound. AB - We developed a modified urethral sound designed for simple insertion of a percutaneous suprapubic cystostomy tube during an operation. The advantages of this instrument are discussed. PMID- 1875499 TI - Filling and voiding pressures measured by ambulatory monitoring and conventional studies during natural and artificial bladder filling. AB - A total of 20 men awaiting elective prostatectomy for bladder outflow obstruction underwent conventional medium filling cystometry and ambulatory monitoring of bladder pressures during natural bladder filling. Total bladder capacity was similar during both tests (medium filling cystometry 256 +/- 138 ml. and ambulatory monitoring 248 +/- 120 ml., p not significant) as was the voided volume (medium filling cystometry 180 +/- 100 ml. and ambulatory monitoring 179 +/- 88 ml., p not significant). However, the peak urinary flow rate at the end of medium filling cystometry (4 +/- 6 ml. per second) was significantly lower than during ambulatory monitoring (9 +/- 4 ml. per second, p less than 0.05). The bladder contraction pressure during medium filling cystometry (79 +/- 44 cm. water) was significantly lower than during ambulatory monitoring (107 +/- 39 cm. water, p less than 0.005). Bladder pressures during voiding recorded after natural filling were significantly greater than after artificial filling. This finding may have significant implications for the use of conventional cystometry to study conditions such as outflow obstruction. PMID- 1875500 TI - Transperineal ultrasonic voiding cystourethrography using a newly devised chair. AB - Using a newly devised chair for transperineal sonography we performed ultrasonic voiding cystourethrography in a total of 219 male patients and volunteers. The study produced adequate images in more than 80% of the people examined. Valsalva's maneuver during urination elicited an intermittent depression of the bladder dome toward the bladder base. In patients with benign prostatic hyperplasia or bladder neck contracture the bladder neck did not open well. Urethral stricture was associated with a marked opening of the bladder neck and posterior urethra. In patients with detrusor-sphincter dyssynergia an involuntary contraction of the external sphincter was observed. These results indicate that this method is useful for screening male patients for diseases causing voiding disturbance and for making differential diagnosis of such diseases. PMID- 1875501 TI - Radial artery hypoplasia: a further association with the VATER syndrome? AB - A case of radial artery hypoplasia in a girl with the VATER syndrome is reported. This finding should alert surgeons dealing with vascular access for dialysis and suggests the possibility of intrauterine ischemia in the etiology of upper limb anomalies in these patients. PMID- 1875502 TI - Segmental renal hypoplasia of vascular origin causing renal hypertension in a 3 year-old girl. AB - A rare case of renal hypertension in a 3-year-old girl caused by segmental renal hypoplasia of vascular origin is presented. Resection of the hypoplastic segment of the kidney permitted successful treatment of the high blood pressure with preservation of renal function. Elevated plasma renin activity in the renal vein of the affected side and biochemical investigations demonstrated that the resected segment of the renal cortex was the source of the renin leading to hypertension by activation of the renin-angiotensin-aldosterone system. PMID- 1875503 TI - A case of vesical paraganglioma behind the symphysis pubis. AB - We report on a 15-year-old boy with a vesical paraganglioma behind the symphysis pubis. Magnetic resonance imaging and transurethral intravesical ultrasonography were helpful in the preoperative localization of the lesion. PMID- 1875504 TI - Chromosomal anomaly and malformation syndrome with abdominal polyorchidism. AB - We describe a neonate who presented with multiple severe malformations including polyorchidism. To our knowledge this is the second case reported with ipsilateral testes located intra-abdominally. Chromosomal studies in cases of polyorchidism have been reported previously only once and the patient exhibited a normal karyotype. Our patient had a chromosome 21 long arm deletion. Interestingly, a trisomy 21 patient has been reported with agonadism. We suggest that genes on chromosome 21 may have some role in gonadal development. PMID- 1875505 TI - Renoduodenal fistula in a patient with chronic nephrostomy drainage: a case report. AB - We describe the occurrence of a renoduodenal fistula related to a nephrostomy tube in a patient with xanthogranulomatous pyelonephritis and renal calculi. The patient was successfully treated by nephrectomy. Etiological, diagnostic and therapeutic aspects are discussed. PMID- 1875506 TI - Recurrent malacoplakia of the female urethra. AB - Malacoplakia, a rare inflammatory lesion, afflicts the genitourinary system in most cases. A 22-year-old women had a recurrence of urethral malacoplakia that had been excised 5 years earlier. The recurrence was accompanied by staphylococcal infection in the urinary tract. The pathological specimens in both instances had the features typical of malacoplakia with von Hansemann cells and Michaelis-Gutmann bodies. PMID- 1875507 TI - Epilation of hair-bearing urethral grafts using the neodymium:YAG surgical laser. AB - Nonhair-bearing skin should be used when grafting is necessary during urethroplasty for stricture or hypospadias repair. Occasionally, this is not possible or hair-bearing skin is used inadvertently. Traditionally, electrocoagulation has been the method used for epilation when intraluminal hair has become a problem, such as interfering with flow, as a focus for recurrent urinary tract infection or acting as a nidus for calculus formation. Electrocautery also is performed during grafting in an attempt to prevent the growth of hair when hair-bearing skin is used. Unfortunately, due to lack of penetration the hair follicles are not destroyed and the epilating procedure fails or is only partially successful. The neodymium:YAG surgical laser can photocoagulate tissue to a depth up to 5.0 mm, and thus, has the ability to destroy hair follicles. We report 4 cases presenting with clinical problems directly related to hair-bearing urethral grafts successfully treated by neodymium:YAG laser epilation. PMID- 1875508 TI - Urethrovaginal reconstruction using a perineal artery axial flap. AB - A 19-year-old woman was born with a cloacal malformation and a common urogenital sinus. We describe a method of urethral and vaginal reconstruction to correct these anomalous problems. A neourethra was constructed from tubularized anterior vaginal epithelium. A perineal artery based axial flap was used to cover the neourethra plus widen the vaginal orifice. PMID- 1875509 TI - Purulent corporeal cavernositis secondary to papaverine-induced priapism. AB - Intracavernous autoinjection of vasoactive substances is used to treat erectile dysfunction. Infection of the corpora cavernosa can be a serious life-threatening complication with this treatment modality. Cavernositis is an unusual complication, especially in otherwise healthy men. In diabetic patients with altered blood supply to the penis and a change of cavernous tissue ischemia can lead to a fulminant infection. We report on a 63-year-old diabetic patient who presented with purulent cavernositis a few weeks after beginning intracavernous injection of papaverine. Treatment included bilateral corporotomy, debridement, and placement of intracorporeal irrigation and suction drains. The patient survived this serious infection leaving both corpora cavernosa with severe fibrosis. PMID- 1875510 TI - Complication of a penile prosthesis reservoir: venous compression masquerading as a deep venous thrombosis. AB - We report a case of vascular compromise secondary to the reservoir of an inflatable penile prosthesis. The problem masqueraded as deep venous thrombosis in the lower extremity of a patient 3 years after a spinal cord injury. PMID- 1875511 TI - Azoospermia: a complication of hydrocele repair in a fertile population. AB - Although minor complications have been reported, hydrocelectomy generally is considered to be a safe procedure. We recently treated 3 patients who became azoospermic after hydrocele repair. Of the patients 2 underwent bilateral and 1 unilateral hydrocelectomy. All 3 patients had iatrogenic injury to the vas deferens or epididymis after hydrocele repair. PMID- 1875513 TI - Re: Corporeal plication for surgical correction of Peyronie's disease. PMID- 1875512 TI - Primary seminoma of the seminal vesicle: report of a case. AB - We report on the clinical and histological findings of a primary extragonadal germ cell tumor that was proved to be a seminoma of the seminal vesicle. The patient had left ureteral obstruction at diagnosis. The testes were normal on physical and ultrasound examination, and the retroperitoneum was free of tumor. There was no recurrence 8 months postoperatively. PMID- 1875514 TI - Re: Small urothelial carcinoma: diagnosis and treatment by cold forceps biopsy. PMID- 1875515 TI - Penile detumescence: characterization of three phases. AB - In 22 dogs in which erection was induced by cavernous nerve stimulation, we analyzed the intracavernous pressure changes during detumescence without and with acute clamping of the aorta or electrostimulation of the lumbar sympathetic chains. Additionally, the degree of venous outflow obstruction was assessed by saline perfusion of the cavernous body during aortic occlusion. Detumescence had three distinct phases: an initial phase exhibiting a small pressure increase; a second phase showing a slow pressure decrease; and a third phase in which a fast decrease occurred. The first phase was abolished by aortic clamping, whereas the other phases were not significantly affected. Sympathetic stimulation abolished or prevented the second phase. Perfusion of the cavernous body during the second phase resulted in a pressure rise to off-scale values; however, when initiated during the terminal phase or in the nonstimulated penis, the pressure increase was slight. Our study indicates that the arterial flow rate influences the duration of the first phase of detumescence and that venous drainage is completely restored in the third phase. Furthermore, sympathetic stimulation causes an almost immediate full restoration of venous drainage, as cavernous perfusion initiated with an intracavernous pressure about twice as high as without sympathetic stimulation failed to increase pressure to off-scale values. PMID- 1875516 TI - Age-related changes in the rat detrusor muscle: the contractile response to inorganic ions. AB - The effect of age on in vitro rat bladder responsiveness function in inorganic ions, CaCl2, KCl, BaCl2 and MgCl2, was investigated, and the results were compared between young (six months old) and aged (16 and 24 months old) rats. In the aged bladders the contractile strength and contractile speed responding to CaCl2 were significantly less compared to the young. On the other hand, the muscle contraction of the three groups following depolarization of the cell membrane by adding KCl and BaCl2 did not differ significantly. The change in muscle relaxation responding to MgCl2 was also insignificant. These results suggest that although contractile and relaxation mechanisms of the detrusor muscle per se are not affected by an aging process, the contractile ability which is related to calcium ion is impaired in the aged rats. It is likely that decreased membrane permeability to calcium ions and/or the change in the intracellular contractile mechanisms related to calcium ions may account for the decreased muscle contractility in the aged rats. PMID- 1875517 TI - Maintenance of erection of penile glans, but not penile body, after transection of rat cavernous nerves. AB - Two experiments tested the widely held assumption that the cavernous nerves (CN) are essential not only to erection of the penile body, via the corpora cavernosa, but also to erection of the glans penis, via the corpus spongiosum. In Experiment 1, the copulatory behavior and reflexive erections of male rats were studied before and after the CN were transected bilaterally (n = 8), unilaterally (n = 6), or sham-operated (n = 6). In postoperative tests, bilaterally operated males were severely impaired in their attempts to effect intromission, and they had the expected deficits in reflexive erections of the penile body, but their capacity for erection of the glans penis was only minimally impaired. Sham-operated males were unaffected by surgery, and unilaterally transected males had intermediate values. Experiment 2 tested the hypothesis that activity of the bulbospongiosus muscles was responsible for the residual erectile capacity of the glans after CN transection in Experiment 1. Males had bilateral sections of the CN (n = 9), or of the nerves innervating the bulbospongiosus muscles (n = 10), or of both of these nerves (n = 8), or sham surgery (n = 10). Relative to CN transection alone, the combined denervation further reduced glans penis erections, but did not eliminate them. These results suggest that the cavernous nerves of the rat are not the only peripheral nerves facilitating vascular engorgement of the corpus spongiosum. PMID- 1875518 TI - Three-D muscular arrangement at the ureteropelvic junction and its changes in congenital hydronephrosis: a stereo-morphometric study. AB - Ureteral walls were obtained from twelve autopsies without urological diseases and from surgical material of twelve patients operated for congenital hydronephrosis. The specimens were submitted to computer-assisted analysis of 3-D muscular architecture at the ureteropelvic junction (UPJ). Serial histologic sections in parallel with the wall were prepared. A geometric model was introduced to simplify the muscular layer, replacing bundles with vectors of corresponding size and direction. The vector distribution visualized that normally, the ureteral muscles change their arrangement with age, from a circular pattern in neonates to an oblique mesh in adults. In addition, longitudinal muscles emerged at the age of two years in the subepithelial layer. In patients with congenital hydronephrosis, not only were such growth-related changes ambiguous or lacking, but there also were various abnormalities; segmental muscular hypoplasia, disarrangement of bundles or lack of longitudinal fibers. These were considered to closely correlate with the urinary obstruction in patients with this disease. PMID- 1875519 TI - Establishment and characterization of a new human prostatic carcinoma cell line (DuPro-1). AB - A new human prostate adenocarcinoma cell line (DuPro-1) has been established from the athymic nude mouse supported xenograft DU5683. This was accomplished by embedding dispersed xenograft cells in 0.1 by 5.0 cm. spaghetti-like strands of Basement Membrane MATRIGEL [BMM (Collaborative Research, Inc.)], a unique technique facilitating the transition to tissue culture. Now passed over 30 times, the cells display anchorage and serum concentration independent growth with a doubling time of 22 to 24 hours. Cells exhibit pronounced morphological differences when grown on BMM coated culture dishes, assuming a pseudoglandular configuration, in contrast to typical homogeneous monolayer growth on plastic culture dishes. Light and electron microscopy show cohesive sheets of anaplastic epithelial cells, consistent with prostate carcinoma. Karyotypic analysis revealed all human chromosomes, near tetraploidy, 10 to 12 markers, and 3 to 4 X chromosomes, without a Y chromosome. Cells injected s.c. or embedded in BMM and implanted in the subrenal capsule space are equally tumorigenic in male and female athymic mice, suggesting that DuPro-1 cells are hormonally insensitive. Embedding cells in BMM may be useful in developing other tissue culture cell lines from neoplasms difficult to initiate in vitro. DuPro-1 should provide a valuable means to study the biology, immunology, and chemosensitivity of human prostate cancer. PMID- 1875520 TI - Characteristics of blood flow velocity patterns of central systemic veins in healthy adults assessed by Doppler echocardiography. AB - To evaluate the differences in shape and phase lag of the flow velocity curves in the superior (SVC) and inferior (IVC) venae cavae and the hepatic vein (HV), Doppler echocardiographic examination was performed in 40 healthy adults (aged 20 to 67 years, mean +/- SD: 39 +/- 12 years). Flow velocity patterns in each vein were characterized by 4 major deflections: S wave, a systolic forward flow; D wave, a diastolic forward flow; A wave, a small backward flow or reduction of diastolic forward flow due to atrial contraction; and O wave, a small backward flow or reduction of forward flow after the second heart sound. Except for a reduced phasic flow in a collapsed IVC, the venous flow velocity recordings in each vein demonstrated very similar pulsatile patterns and small differences in mean time lags of less than 50 msec. In general, the lowest values of peak A/peak S, peak O/peak S and peak D/peak S were observed in HV flow and the highest in IVC flow. Backflows of A and O waves were prominent in HV flow, but small and least frequent in IVC flow. These data suggest that the baseline of the central venous flow recordings might shift downward in HV flow and upward in IVC flow. However, even if both the baseline shift and amplitude of the flow curve were normalized in each venous flow velocity curve, apparent differences in shape of the flow velocity curves would remain. We concluded that the characteristics and differences of each central venous flow velocity pattern should be noted in studies of these areas. PMID- 1875521 TI - Evaluation with Fourier analysis on radionuclide angiography of viable but stunned myocardium in patients with right ventricular myocardial infarction. AB - Stunned myocardium of right ventricle was studied by radionuclide angiography (RNA) and Thallium myocardial scintigraphy (TL) in 39 patients with inferior myocardial infarction with and without right ventricular myocardial infarction (RVMI). RNA was performed within 1 week of the onset (acute phase) and after 1 month, when exercise cardiac scintigraphy (EX-TL) was also performed. The ejection fraction (EF) of each ventricle calculated from RNA and the phase and amplitude evaluated visually and quantitatively by Fourier analysis were compared between the acute phase and 1 month after the onset of myocardial infarction. The degree of visualization of right ventricle was examined in EX-TL 1 month after the onset. (1) In RNA obtained in the acute myocardial infarction, abnormalities in the right ventricle (delayed phase or low amplitude image) were observed in 18 (46%) but not in 21 (54%) of the 39 patients (N group). Of those 18 patients, the abnormalities in the right ventricle alleviated in 11 (RVMI-A group) but persisted in 7 (RVMI-B group) in RNA obtained 1 month after the onset. (2) In the acute phase, the right ventricular ejection fraction (RVEF) was 39.4 +/- 10.4% in N group, 30.8 +/- 5.3% in RVMI-A group, and 29.6 +/- 8.9% in RVMI-B group, with significant differences between N group and the other two groups (P less than 0.05) but no significant difference between RVMI-A and RVMI-B groups. (3) After 1 month, RVEF was 40.1 +/- 10.1% in N group, 42.2 +/- 8.4% in RVMI-A group, and 32.2 +/- 9.8% in RVMI-B group, being improved in RVMI-A group and showing a significant difference as compared with RVMI-B group (p less than 0.05). (4) In EX-TL of RVMI-A group, the right ventricle was visible although the uptake of TL was reduced in the entire right ventricle. In RVMI-B group, only part of the right ventricular free wall was visible with defects in the other areas of right ventricle. The sign of RVMI showed improvements in many of the patients after the acute phase, and their condition was considered to have been so-called stunned myocardium, which is a complex of symptoms of reversible myocardial ischemia, rather than RVMI. PMID- 1875522 TI - Comparative study between St. Jude Medical and bioprosthetic valves in the right side of the heart. AB - Comparative long-term performance characteristics of St. Jude Medical (SJM) and bioprosthetic valves were conducted retrospectively for patients who underwent prosthetic valve replacement in the right side of the heart from 1975 to 1988. Fifty-four patients received either SJM (n = 18) or bioprosthetic (n = 37) valves. The cumulative follow-up for SJM valves was 91 valves-years (range 3.9 to 7.2 years) and that for bioprostheses was 282 valve-years (range 1.3 to 14.8 years). Follow-up rate was 100%. The actuarial survival rate excluding hospital deaths at 5 years was 81 +/- 10% for SJM and 97 +/- 3% for bioprosthetic valve recipients (p = ns). The rates of freedom from thrombosis or anticoagulant related hemorrhage, structural valve failure, prosthetic valve endocarditis, reoperation, and overall valve-related complications at 5 years were 72 +/- 11%, 100%, 100%, 83 +/- 9%, and 72 +/- 11% for SJM valve recipients, and 100%, 97 +/- 3%, 97 +/- 3%, 94 +/- 4%, and 94 +/- 4% for bioprosthetic valve recipients, respectively. Structural valve failure, prosthetic valve endocarditis and reoperations occurred at a similar incidence in each of the two types of prostheses. Thrombosis and overall valve-related events occurred more frequently in SJM valve recipients (5.5 +/- 2.5 vs 0%/valve-year; p less than 0.02, 6.6 +/- 2.7 vs 1.1 +/- 0.6 %/valve-year; p less than 0.03, respectively). The bioprosthetic valve which did not need warfarin anticoagulation therapy had low incidence of valve-related complications and showed good long-term durability even in the younger age group. The bioprosthetic valve was superior to the SJM valve in the right side of the heart. PMID- 1875523 TI - Intraaortic balloon entrapment--a case report and a review of the literature. AB - A case of intraaortic balloon entrapment is reported. To our knowledge, this is the tenth case in the literature. We conclude that balloon entrapment can occur without any signs of rupture of the balloon and that the balloon should be removed surgically. PMID- 1875524 TI - Pressure-volume relationships of finger arteries in healthy subjects and patients with coronary atherosclerosis measured non-invasively by photoelectric plethysmography. AB - Knowledge of the mechanical properties of the small arteries is important for understanding physiological and pathophysiological conditions in the human peripheral circulation. We have recently developed a new method for the noninvasive measurement of arterial elastic properties in human fingers using photoelectric plethysmography. In this study, the pressure-volume relationship, an index for expressing arterial elasticity, was measured by this method in the finger arteries of 91 healthy subjects and 102 patients with coronary artery disease. Aging effects on the elastic properties of finger arteries were examined in healthy subjects classified into three groups: under 30, 31-49, and over 50 years of age. The pressure-volume curve shifted downward with increase in age, indicating that the elasticity of finger arteries decreased with age. Patients with 75% or greater coronary stenosis, as compared with age-matched healthy subjects, showed distinctly lower elasticity of finger arteries. As the number of diseased coronary arteries increased, the elasticity of finger arteries tended to decrease steadily. The elasticity of finger arteries decreased in coronary disease patients with hypertension much more than in those without hypertension. These results suggest that age-related changes in arterial elasticity can occur in peripheral small arteries, and that peripheral arteries in patients with coronary atherosclerosis are less elastic than those in healthy subjects. PMID- 1875525 TI - Assessment of superior vena caval blood flow velocity in ischemic heart disease. AB - In order to evaluate the right atrial function in patients with ischemic heart disease, we studied the superior vena caval blood flow velocity using pulsed Doppler echocardiography. The subjects included 31 patients with anteroseptal infarction (ANT), 23 with inferior or inferoposterior infarction (INF + POS), 27 with effort angina pectoris (EAP) and 15 with vasospastic angina pectoris (VAP). The systolic peak flow velocity (PFVs) was significantly reduced only in INF + POS compared with those in ANT, EAP and VAP (36.8 +/- 1.8 cm/sec vs 46.9 +/- 2.1 cm/sec, 46.4 +/- 2.1 cm/sec and 42.6 +/- 1.9 cm/sec, p less than 0.05, respectively). No significant difference in diastolic peak flow velocity (PFVd) was found between the 4 groups. PFVs/PFVd was significantly reduced only in INF + POS compared with those in ANT, EAP, and VAP (1.39 +/- 0.05 vs. 1.75 +/- 0.08, 1.76 +/- 0.09, and 1.62 +/- 0.09, p less than 0.05, respectively). These results suggested that INF + POS caused impairment of the right atrial reservoir function. PMID- 1875526 TI - Myocardial blood flow, alternans of ST segment elevation, conduction delay and ventricular arrhythmia during acute myocardial ischemia with and without retrograde blood flow in canine hearts. AB - The technique of retrograde blood flow has been shown to decrease collateral flow into the ischemic myocardium, and to cause severe myocardial ischemia in dogs. Ischemia with retrograde blood flow in dogs is similar to ischemia in human hearts. Therefore, we examined the effect of retrograde blood flow on myocardial blood flow, ST segment elevation, alternans of ST segment elevation, conduction delay and ventricular arrhythmia in dogs. Sixty dogs were divided into two groups. In group A (N = 32), the left anterior descending coronary artery was occluded for 10 min. In group B (n = 28), ischemia was induced by the technique of retrograde blood flow for 10 min. During ischemia, the myocardial blood flow at the ischemic zone measured by a H2 gas clearance method was 11.2 +/- 1.6 in group A and 5.7 +/- 0.7 ml/min/100 g in group B (p less than 0.01). The maximal ST segment elevation was 13.6 +/- 1.9 in group A and 27.2 +/- 2.1 mV in group B (p less than 0.001); the maximal alternans of ST segment elevation was 5.3 +/- 1.1 in group A and 10.1 +/- 1.4 mV in group B (p less than 0.01); the maximal conduction delay was 51.6 +/- 8.4 in group A and 111.1 +/- 6.2 msec in group B (p less than 0.001); and the incidences of ventricular premature beats (greater than 5/min), ventricular tachycardia and fibrillation were 34%, 41% and 22% in group A, and 68%, 79% and 25% in group B (p less than 0.01, p less than 0.01 and not significant, respectively). It is concluded that ischemia with retrograde blood flow can be used to examine occlusive and reperfusion ventricular arrhythmia in dogs, because the incidences of ventricular premature beats and ventricular tachycardia were high, but that of ventricular fibrillation was not high despite the severe ischemia. PMID- 1875527 TI - A comparison of excimer laser, thermal probe, and mechanical devices for recanalizing occluded human arteries. AB - To evaluate the mechanism of excimer laser recanalization and compare the results with those of laser-assisted thermal probe recanalization and mechanical recanalization, a total of 42 human atherosclerotic totally occluded arterial segments (2-15 cm long) were recanalized by excimer laser with a 400-800 micron quartz fiber pulsed at 20 Hz with 50 mJ/mm2 of energy (n = 21), an Argon heated thermal probe at 10-12 watts (n = 11), a guidewire directed through a 6 Fr multipurpose catheter, or an angioplasty balloon catheter (n = 10). On histologic examination, the excimer laster created a single round lumen or multiple lumens ("Swiss-cheese" like appearance) with no evidence of thermal injury at the perimeter of the lumen. The incidence of perforation in vitro was less with an excimer laser catherter (8/21 or 38%) than with the thermal prove (10/11 or 91%) (p less than 0.01). However, serial histologic cross-sectional examination showed that the pathway of the devices were essentially the same in all recanalization procedures. The pathway of the device was located outside the atheroma but proximal to the internal elastic membrane in 13 arteries with the excimer laser (62%), in 10 arteries with the thermal probe (91%), and 8 arteries with mechanical devices (80%). These results indicate that although the eximer laser could recanalize human atherosclerotic arteries without thermal injury, the fiber frequently deflected around firm atherosclerotic plaque and advanced in a dissection plane between the plaque and media. A similar course was noted for the thermal probe or during mechanical recanalization with a guidewire and catheter. To insure the safety of an excimer fiber or a thermal probe to reopen complete occlusions, better guidance systems must be developed. PMID- 1875528 TI - Effects of residual coronary stenosis on myocardial salvage after reperfusion in dogs. AB - In order to study the effects of residual stenosis on myocardial salvage, we created 99% coronary stenosis with or without contrast washout delay at reperfusion in six groups of dogs. In Group A (n = 8), the artery was occluded for 1h before being fully reperfused. In Group B (n = 9), the artery was occluded for 1h, then subjected to 6h of 99% stenosis without contrast washout delay. In Group C (n = 8), the artery was occluded for 1h, followed by 1 week of 99% stenosis without contrast washout delay. In Group D (n = 10), again the artery was occluded for 1h, then subjected to 6h of 99% stenosis with contrast washout delay. In Group E (n = 8), the artery was occluded for 7h, then fully reperfused for 1 week. Finally, in Group F (n = 8), the occlusion lasted for a full week. All dogs were sacrificed 1 week after occlusion. In Group A, myocardial creatine phosphokinase activity (CK) in the inner layer was 43.8 +/- 12.5% that of non infarcted myocardium. Myocardial CK in Group B (46.5 +/- 7.4%) was little different but in Group C it dropped to 26.6 +/- 8.4%, suggesting that 99% residual stenosis is not deleterious if it is continued for 6h or less but that it will result in considerable depletion of myocardial CK, it is is sustained for 1 week. In Group D, myocardial CK dropped markedly to 11.3 +/- 3.7%, little different from that for either Group E (13.3 +/- 2.6%) or Group F (9.3 +/- 3.3%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875529 TI - The role of oxygen free radicals and extracellular calcium ions in reperfusion induced arrhythmias. AB - To examine the role of oxygen free radicals and extracellular calcium ions in reperfusion-induced ventricular arrhythmias, we evaluated the effects of hypoxic reperfusion, oxygen free radical scavengers, allopurinol and hypocalcemic reperfusion on reperfusion-induced ventricular arrhythmias. The hearts of male Sprague-Dawley rats were perfused in the working heart mode. Whole heart ischemia was induced for 15 min and then reperfused. Rats were divided into 5 groups: control group, scavenger group, allopurinol group, hypoxia group and hypocalcemia group. Scavenger, hypoxic and hypocalcemic perfusions were undertaken only during the period of perfusion. The incidence of reperfusion-induced ventricular fibrillation (Vf) was reduced in the scavenger group (100% to 38%) and the hypoxia group (100% to 50%). Spontaneous reversion of Vf to regular sinus rhythm was recognized in the hypoxia and hypocalcemia groups. In conclusion, oxygen free radicals would play an important role in the genesis of the reperfusion arrhythmias, and extracellular calcium concentration would also play an important role in sustaining the reperfusion arrhythmias. Notably, hypoxic reperfusion had protective effects on both processes. PMID- 1875530 TI - Effects of nifedipine on diastolic abnormalities in low-flow and pacing-induced ischemia in isolated rat hearts. AB - An animal experimental model which stimulates human effort angina, especially in terms of diastolic abnormalities, was developed using isovolumically beating perfused rat hearts. Using this model, we studied the effects of nifedipine, a Ca2+ channel blocker, on diastolic properties during pacing-induced ischemia. When the preload of the left ventricle was set at a low level, low-flow ischemia (coronary perfusion pressure of 40 mmHg) plus tachycardia (480 beats/min for 4 min) did not induce an increase in left ventricular end-diastolic pressure (LVEDP). However, with a high preload, low-flow ischemia plus pacing tachycardia induced an increase in LVEDP of 8.4 +/- 5.4 mmHg (p less than 0.01) and a prolongation of the time constant of ventricular pressure decline (6.8 +/- 4.6 msec, p less than 0.05) immediately after pacing tachycardia. Pretreatment with nifedipine (3 x 10(-8) M) prevented the rise in LVEDP induced by pacing tachycardia. Thus, in isolated perfused hearts, diastolic abnormalities similar to those seen in angina pectoris were obtained by low-flow ischemia plus pacing tachycardia. The response to nifedipine suggested that an alteration of Ca2+ movement may play an important role in the increase in left ventricular stiffness under these conditions. PMID- 1875531 TI - Serum from patients with restenosis after percutaneous transluminal coronary angioplasty stimulates proliferation of bovine vascular smooth muscle cells under low extracellular calcium condition. AB - We compared the effects on the proliferation of bovine vascular smooth muscle cells (VSMC) of serum from 36 patients without restenosis (group A), and 21 patients with restenosis (group B) after percutaneous transluminal coronary angioplasty (PTCA). Baseline characteristics were similar in both groups, except for the greater number of patients with unstable angina at the time of PTCA (52 vs 22%, p = 0.020) and the shorter interval between PTCA and repeat angiography in group B (106 +/- 30 vs 153 +/- 112 days, p = 0.022). Cultured bovine VSMC were stimulated with patient serum (5%) obtained at repeat angiography in either Ca(2+)-containing or Ca(2+)-free culture medium. DNA synthesis was assessed by [3H]thymidine incorporation. The following indices of VSMC proliferation were used: S(+) = [3H]thymidine uptake stimulated by 5% serum in Ca(2+)-containing medium/[3H]thymidine uptake stimulated by 5% fetal calf serum (FCS) in Ca(2+) containing medium, S(-) = [3H]thymidine uptake stimulated by 5% serum in Ca(2+) free medium/[3H]thymidine uptake stimulated by 5% FCS in Ca(2+)-free medium, and D = S(-)-S(+). D represented the preserved DNA synthesis in Ca(2+)-deprived medium. S(-) was lower than S(+) in group A (1.35 +/- 0.56 vs 1.57 +/- 0.58, p less than 0.0001), whereas it was higher than S(+) in group B (1.64 +/- 0.66 vs 1.50 +/- 0.58, p = 0.010). D was significantly higher in group B than in group A (0.14 +/- 0.23 vs -0.22 +/- 0.28, p less than 0.0001), and was not associated with any continuous variables including serum calcium level on univariate regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875532 TI - [Pain assessment using fuzzy set theory]. PMID- 1875533 TI - [Changes in the water-electrolyte balance and kidney function in the elderly]. PMID- 1875534 TI - [Hemodynamic effects of endothelin in anesthetized dogs]. AB - The purpose of the present study was to investigate and compare the hemodynamic responses that can be elicited in anesthetized dogs by intravenous administration of endothelin at rates of 300 (group E-I, n = 9) and 600 pmol.kg-1 (group E-II, n = 9) for 15 minutes. In group E-I, no significant pressure response was observed after administration of endothelin and cardiac index remained unchanged throughout the experiment. However, right and left ventricular work indices increased significantly but left ventricular maximum dp/dt and pulmonary vascular resistance decreased significantly. In group E-II, mean arterial pressure increased significantly by elevating systemic vascular resistance with marked decrease in cardiac index. However, right and left ventricular work indices remained unchanged throughout the experiment. On the other hand, each dose of endothelin significantly increased pulmonary capillary wedge pressure and left ventricular end-diastolic pressure but decreased heart rate. The present data revealed that the hemodynamic effects were different according to the doses of endothelin infused. In conclusion, our results show that endothelin (600 pmol.kg 1 BW) produces a long lasting increase in arterial pressure and endothelin induced pressure responses are caused by an elevation in systemic vascular resistance. PMID- 1875535 TI - [The effect of inhalation of sevoflurane for an hour on the liver of beagles]. AB - The effect of sevoflurane in comparison with that of enflurane and halothane, each at 1.8 MAC, on the liver was examined after inhalation exposure to beagles under controlled respiration for 1 hr. No abnormalities were observed in general conditions in the animals exposed to any of these anesthetics. Recovery time to spontaneous respiration after the end of anesthesia was similar for each group, but the awakening was quickest in sevoflurane exposed group. Blood pressure dropped immediately after the initiation of exposure in each group, but it recovered quickly to preexposure levels after the end of the exposure. Minor and reversible elevations in the values of GOT, GPT, LDH and bilirubin were noted without the organic change of the liver in beagles after the inhalation exposure to 1.8 MAC of each anesthetic. Since similar changes were observed in beagles exposed to enflurane or halothane, we conclude that no change in the liver specifically associated with sevoflurane was found under these experimental conditions. PMID- 1875536 TI - [Clinical studies on the risk of aspiration pneumonitis with respect to gastric pH and volume--effects of age, induction time, H2-blocker and anesthetic technique]. AB - The age-related risk of aspiration pneumonitis was studied by measuring gastric pH and volume in patients undergoing elective surgery. Control group (without administration of H2-blocker) showed the greatest risk in 12-19 yr sub-group, and the risk decreased with age. Famotidine (H2-blocker) was very useful for premedication in patients of all ages, though slightly uncertain in 12-19 yr sub group. In 12-19 yr sub-group, the proportion of patients with gastric fluid volume greater than or equal to 0.4 ml.kg-1 was significantly greater in PM group (induction of anesthesia in the afternoon) than AM group (in the morning). Furthermore, the effects of anesthetic technique on gastric pH were examined. Gastric pH increased significantly during N2O-O2-halothane and N2O-O2-enflurane anesthesia; while during N2O-O2-epidural and N2O-O2-fentanyl anesthesia, gastric pH was unchanged significantly and stayed low. PMID- 1875537 TI - [Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--7. Effects on natural killer cell activity]. AB - Twenty four patients who underwent ophthalmic surgery were studied to evaluate activities of natural killer (NK) cells during and following total intravenous anesthesia with droperidol, fentanyl and ketamine. They were divided into three equal groups according to anesthetic methods employed. In enflurane group, anesthesia was induced with thiopental 5 mg.kg-1 and succinylcholine 1 mg.kg-1, and maintained with 1-2% enflurane, nitrous oxide (50%) and oxygen (50%). In original NLA group, anesthesia was induced as above and maintained with droperidol 0.15 mg.kg-1, fentanyl 5-10 micrograms.kg-1, nitrous oxide (70%) and oxygen (30%). The patients of total intravenous anesthesia group received droperidol 0.15 mg.kg-1, ketamine 2 mg.kg-1 and succinyl-choline 1 mg.kg-1 for induction of anesthesia, and then were given fentanyl 5-15 micrograms.kg-1, ketamine 2 mg.kg-1.hr-1 and oxygen (30%) for the maintenance of anesthesia. Vecuronium was given to every patient of the three groups for intraoperative muscle relaxation. Hartmann's solution was used at a speed of 5 ml.kg-1.hr-1. Peripheral venous blood 10 ml was drawn on six occasions during and after the surgery for the measurement of NK cell activities and endocrine response as judged by plasma catecholamine and cortisol levels. NK cell activities decreased significantly on the first post-operative day in enflurane group, but no significant differences were found among three groups in NK cell activities. The data suggest that inhaled anesthetics should not be easily employed for patients with depressed immune response, malignant disease and prolonged surgery. PMID- 1875538 TI - [The effects of thromboxane receptor antagonist on hemodynamic responses after neutralization of heparin by protamine]. AB - In a double blind test, the effects of ONO 3708, thromboxane A2 (TXA2) receptor antagonist, on hemodynamic responses after neutralization of heparin by protamine, were evaluated in 19 patients undergoing coronary artery bypass graft. Severe circulatory disturbances were not observed in all patients after intravenous administration of protamine (3 mg.kg-1) over 5 minutes, and in particular ONO 3708 (2.5 micrograms.kg-1.min-1 given with continuous infusion) group (n = 10) showed no deleterious hemodynamic responses to protamine. On the other hand, in placebo group (n = 9) the mean pulmonary artery pressure (mPAP) and the mean pulmonary/systemic artery pressure ratio (Pp/Ps) increased significantly, immediately following protamine administration, compared with the baseline values and ONO 3708 group. The results suggest that pulmonary hypertension after protamine is associated with TXA2 release and that ONO 3708 is useful to avoid this reaction. PMID- 1875539 TI - [Effects of halothane and barbiturate on hepatic circulation and hepatic oxygen metabolism during hypoxia in dogs]. AB - Hepatic oxygen metabolism and the hepatic energy charge were assessed in 21 mongrel dogs receiving 1 to 1.5 MAC of halothane or thiamylal (20-30 mg.kg-1.hr 1) intravenously while inhaling graded hypoxic mixtures (FIO2 0.21-0.08). Hepatic blood flow was measured using electromagnetic flowmetry: hepatic oxygen delivery and consumption were calculated from measured hepatic blood flow and oxygen content in hepatic arterial, portal venous blood and hepatic venous blood. In the hypoxia-halothane group, portal venous blood flow (FIO2 0.15-0.10), portal venous oxygen content (FIO2 0.10-0.08) and hepatic oxygen consumption (FIO2 0.08) significantly decreased compared with the hypoxia-thiamylal group. Arterial ketone body ratio (AKBR), which indicates the mitochondrial energy charge level, decreased with the development of hypoxia, and in the hypoxia-halothane group, the decrease of AKBR was significantly greater than in the hypoxia-thiamylal group at FIO2 0.08. The serum catecholamine levels, epinephrine and norepinephrine, increased in both groups at FIO2 0.08. In the hypoxia-halothane group, however, the increase of norepinephrine was significantly higher than in the hypoxia-thiamylal group at FIO2 0.08. These results suggest that, compared with halothane, thiamylal could suppress the exaggerated reaction to hypoxic hypoxemia, maintain hepatic circulation and hepatic oxygen metabolism and therefore maintain the hepatic mitochondrial redox state in better condition. PMID- 1875540 TI - [Effects of intravenous lidocaine administration on auditory brainstem response]. AB - The effect of lidocaine on the auditory brainstem response (ABR) was investigated in 14 neurologically normal patients. Lidocaine 1.5 mg.kg-1.min-1 was injected intravenously over a 5 min period immediately followed by a continuous infusion of lidocaine 60 micrograms.kg-1.min-1. The seven peak latencies (waves I-VII) and amplitudes (waves I-VII) of the ABR were recorded before and 7-8 min after lidocaine infusion. Peak latencies of waves IV, V, VI, VII increased after epidural anesthesia compared with control values. Amplitudes of all waves were unchanged following intravenous lidocaine injection compared with control values. Interpeak latencies (I-II, II-III, III-IV, IV-V, V-VI, VI-VII), of every second peak (I-III, II-IV, III-V, IV-VI, V-VII), of every third peak except (III-VI, IV VII) were unchanged compared with control values. Interpeak latencies of every fourth peak, of fifth peak increased after lidocaine injection compared with control values. The data obtained in this study with lidocaine injection were similar to the data after epidural anesthesia with lidocaine. One of the reason of the latency changes of ABR after epidural anesthesia was the systemic effect of lidocaine absorbed intravenously from the epidural space. PMID- 1875541 TI - [Blood biochemistry during acidosis associated with ATP-induced hypotensive anesthesia]. AB - Several investigators reported metabolic acidosis during ATP-induced hypotensive anesthesia. To elucidate the etiology, we studied blood biochemistry during hypotensive anesthesia for tympanoplastic surgery. The blood concentration of lactic acid, uric acid, phosphoric acid and carbonic acid increased and their total amount coincided with the base excess change. We also found that metabolic intermediates of glycolysis and of the catabolic pathway of adenosine also increased proportionally. The result suggests that the metabolic change is caused by lactic acid produced from glycolysis promoted by ATP and by the catabolic products of administered ATP itself. PMID- 1875542 TI - [The effect of continuous epidural infusion of a combination of 1% mepivacaine and buprenorphine for post-operative pain relief]. AB - Using a portable 2 ml.hr-1 type infusor (Baxter Infusor), the effect of continuous epidural infusion for post-operative pain relief for 72 hours was studied in 32 patients after upper abdominal surgery. The patients were randomly allocated into four groups: Group 1 (n = 8) received continuous epidural infusion of 1% mepivacaine and buprenorphine 0.2 mg (48 ml.hr-1); group 2 (n = 8) 1% mepivacaine and buprenorphine 0.4 mg (48 ml.hr-1); Group 3 (n = 8) saline and buprenorphine 0.2 mg (48 ml.hr-1); Group 4 (n = 8) saline and buprenorphine 0.4 mg (48 ml.hr-1). The effect was evaluated at intervals of 12-hour until 72 hours postoperatively. Patients received supplemental buprenorphine intramuscularly as needed. In each period during the 12 to 72-hour after operation, the percentage of the patients who needed no supplemental buprenorphine was 62.5-100%, which is higher than during the 0 to 12-hour (25.0%). The percentage of the patients who showed no pain on coughing and changing in position in Group 1 and 2 was higher than in Group 3 and 4 in each period (P less than 0.05 12-24 and 36-72 hr). Continuous epidural infusion using Baxter Infusor with the combination of 1% mepivacaine and buprenorphine is effective for alleviating postoperative pain during the 12 to 72 hours after the operation, and for prevention of pulmonary complications. PMID- 1875543 TI - [The evaluation of incremental positive end-expiratory pressure on right ventricular hemodynamics as determined by the thermodilution technique]. AB - Effects of incremental positive end-expiratory pressure (PEEP) on right ventricular (RV) hemodynamics were studied in 10 patients undergoing coronary artery bypass grafting, abdominal aneurysmectomy and partial hepatectomy, using Swan-Ganz catheter mounted with the rapid response thermistor. PEEP was increased from 0 (baseline) to 15 cmH2O with increment of 5 cmH2O, and right ventricular ejection fraction (RVEF), RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), and cardiac output (CO) were computed with a thermodilution technique at each PEEP. At 15 cmH2O PEEP, RVEF, RVEDVI and RVESVI were comparable with the baseline, while right arterial pressure, RV peak systolic pressure and mean pulmonary arterial pressure increased significantly compared with the baseline. Increased afterload of RN caused by PEEP did not affect RV contractility. Decreased cardiac and stroke volume indices were attributed to the decrease of preload caused by the increase of intrathoracic pressure. We conclude that PEEP at 5 to 15 cmH2O does not influence right ventricular hemodynamics, and RVEDV is a reliable index to monitor RV hemodynamics instead of right arterial pressure to determine optimal PEEP. PMID- 1875544 TI - [Effects on hemodynamics and myocardial metabolism of prostaglandin E1 and trimethaphan after a descending aorta cross-clamp in experimentally coronary constricted dogs]. AB - We investigated the hemodynamic effects of prostaglandin E1 (PGE1) and trimethaphan (TMP) during cross-clamp of the descending aorta in experimentally coronary constricted dogs. Using 21 mongrel dogs, the blood flow of the left anterior descending coronary artery was reduced to 50% by constricting the artery. After stabilization of hemodynamics, we cross-clamped descending aorta and administered PGE1 (1.0 microgram.kg-1.min-1) or TMP (5.0 micrograms.kg-1.min 1). The drugs were discontinued just before the clamp on the aorta was released. In the PGE1 group, cardiac output (CO) and left ventricular dp/dt (LVdp/dt) increased significantly 5 minutes after clamping, with CO remaining at its high level even after the clamp was released. In the TMP group, CO increased significantly 15 minutes after administration and returned to the preclamping value soon after declamping. LVdp/dt was unchanged during clamping and decreased significantly after declamping. In addition, marked increase of the myocardial blood flow (MBF) in the ischemic areas was seen in the PGE1 group, whereas no changes were seen with the TMP. In the ischemic heart, PGE1 can not only decrease afterload which is elevated by the cross-clamping of the aorta, but also increase the coronary blood flow and MBF in the ischemic areas. PMID- 1875545 TI - [Anesthetic management of pheochromocytoma by continuous intravenous injection of prostaglandin E1]. AB - We had five cases of surgical removal of pheochromocytoma by continuous intravenous injection of prostaglandin E1. During anesthesia, we used Swan-Ganz catheter for circulatory monitoring and measured plasma catecholamines. When PGE1 dose was increased from 0.05 to 0.1 and 0.15 microgram.kg-1.min-1, total systemic vascular resistance and mean arterial pressure were decreased but heart rate and cardiac output were not significantly altered from the preanesthetic values. Plasma catecholamines were also similar to the preanesthetic values. Therefore, the results suggest that the mechanism of suppression of hypertension by PGE1 is by affecting vascular beds directly rather than by diminishing catecholamine excretion from sympathetic nerve and adrenal medulla. During manipulation of pheochromocytoma, mean arterial blood pressure increased extremely. Although PGE1 was injected at a rate of 0.3 to 0.5 microgram.kg-1.min-1 in some cases, we could not suppress the elevation of blood pressure. PGE1 alone could not normalize blood pressure and heart rate, and other cardiovascular agents were necessary. PMID- 1875546 TI - [The anesthetic management of a patient with the malignant hyperthermia trait diagnosed preoperatively]. AB - A patient for fixation of ankle arthrodesis diagnosed as having malignant hyperthermia trait preoperatively is reported. A 17 year old man was anesthetized with enflurane for orthopedic surgery of the knee joint. At that time malignant hyperthermia developed. He was critically ill, but resuscitated and recovered from acute renal failure on 7th day after operation. Ca2+ release test was performed. Ca2+ releasing speed was prominently accelerated in this patient. We could identify him as having malignant hyperthermia trait. Epidural anesthesia with procaine chloride was given cautiously. No drug which may induce malignant hyperthermia was used. Nevertheless, malignant hyperthermia occurred. This disease has various forms of presentation. The mechanism is equivocal, and in some cases, it is difficult to judge it immediately. This patient was managed without complication. We consider that tourniquet and stress provoked signs of malignant hyperthermia in this patient. PMID- 1875547 TI - [Prevention of hypertension at intubation with intravenous nicardipine]. AB - We administered a calcium channel blocker, nicardipine 0.01 mg.kg-1 i. v. bolus or 5 micrograms.kg-1.min-1 i. v. infusion before induction with thiamylal or modified NLA (thiamylal, droperidol and butorphanol) to prevent hypertension at intratracheal intubation, and measured blood pressure and heart rate before and after intubation. Blood pressure of all experimental groups was significantly reduced in comparison with the control group right after intubated. Nicardipine is effective to prevent hypertension at intubation. PMID- 1875548 TI - [Ventricular arrhythmia associated with the use of an electrosurgical unit in a patient with a Swan-Ganz catheter]. AB - We experienced short-run type ventricular arrhythmia associated with use of electrosurgical unit (ESU) in a patient with a Swan-Ganz catheter. Leakage current was not detected from the body of the five different devices used in this study. Nevertheless, there is a possibility of leakage current to the electrode of the intra-cardiac catheter thereby exciting the myocardium, because the grounding of the five devices used simultaneously on the patient were not of EPR system. The other possibility, that is the occurrence of pulse direct current voltage by rectification of high frequency current at the contact point of electrosurgical knife's tip and vital organ is a speculation but not underlined by a definite proof. In summary, the cause of ventricular arrhythmia associated with the use of ESU could not be identified in the present case. It must always be remembered that whatever safety measures may be prescribed for electrical instruments, a complete prevention of EMI is impossible. Also it must be stressed that whenever many devices are used simultaneously on a patient, EPR system is very important for avoiding electrical hazard. PMID- 1875549 TI - [Severe bradycardia and hypotension during spinal anesthesia: a report of five cases without morbidity]. AB - We reported five cases of sudden onset of bradycardia and hypotension during spinal anesthesia in which measurable parameters of the patients were monitored continuously by inter-operating-room local area network system. In the first two cases, episodes of bradycardia and hypotension were caused by incomplete spinal blockade. In the third patient, severe bradycardia was preceded by gradual decrease of heart rate following high spinal blockade. In the last two cases of high spinal anesthesia, no remarkable change of the heart rate was observed before sudden onset of bradycardia and hypotension. All five patients were easily and adequately treated and they showed no signs of hypoxia. We would like to emphasize the importance of adequate and continuous monitoring during spinal anesthesia. PMID- 1875550 TI - [Malfunctioning of infusion pumps due to interference from an electrosurgical unit]. AB - We observed the incidence of pump errors by the interference from the electrosurgical unit (Vallylab, Force 4B) set at coagulation or cut mode, with three infusion pumps: Terumo STC-523, STC-525 and STC-525-01. The STC-525-01 painted with electrically conductive paint inside was used during electrosurgery on experimental basis. Malfunctioning of the STC-523 pump occurred frequently by using electrosurgical unit set at coagulation mode and placed close to the pump. The STC-525-01 showed markedly lower incidence of malfunctioning. Therefore, the STC-252-01 pump can be used safely during electrosurgery. Additionally, we discovered, through an estimation of radiated electrical field around the electrosurgical unit, the cable of an active electrode was important as an interference source. To minimize electrosurgical interferences, we propose the following recommendations; 1) keeping the infusion pump and its AC line as far as possible from the active electrode cable, 2) keeping the output of electrosurgical unit as low as possible, 3) operating the pump with its internal battery power supply, and 4) monitoring the operation of the pump while using electrosurgery. PMID- 1875551 TI - Serologic evidence of toxocariasis in northeast Brazil. AB - Sera from 54 Brazilian children with a history of tropical eosinophilia syndrome were screened for toxocariasis. The enzyme-linked immunosorbent assay detected 21 positive sera (40%). Many of these cases (15 of 21) were positive for Dilofilaria immitis as well. Of the six Toxocara-positive children with hypereosinophilia, two were asthmatic. Their sera were further examined by the Toxocara species specific Ouchterlony's diffusion-in-gel test and one Toxocara canis and one T. cati infections were identified. This is the first report of serologically diagnosed toxocariasis in Brazil. PMID- 1875552 TI - Effects of hyperlipaemic serum on interleukin-2 (IL-2) production, IL-2 receptor expression, and T cell proliferation induced by IL-2 in cynomolgus monkeys. AB - The effect of hyperlipaemic serum on mitogen-induced T lymphocyte proliferation was investigated with cynomolgus monkeys. The mitogen-induced blastogenesis was remarkably inhibited when either hyperlipaemic or normal monkey lymphocytes were incubated with hyperlipaemic sera. Hyperlipaemic serum also inhibited ConA induced interleukin 2 (IL-2) production as well as IL-2 receptor (IL-2R) expression of normal monkey lymphocytes. On the other hand, it showed slight inhibition of T-cell proliferation induced by adding recombinant human IL-2 to IL 2R-positive normal monkey lymphocytes. These results indicate that hyperlipaemic serum inhibited an early stage of T-cell autocrine activation pathway including IL-2 production and IL-2R expression. PMID- 1875553 TI - Evaluation of microbial metabolites for trypanocidal activity: significance of biochemical and biological parameters in the mouse model of trypanosomiasis. AB - Trypanosomiasis is a parasitic disease, prevailing in both humans and animals, caused by a single-cell parasite, Trypanosoma spp. Three microbial metabolites, namely antiamoebin, F-857 and 6-MFA, were evaluated for trypanocidal activity by using a mouse model of trypanosomiasis, which is caused by T. evansi. The significance of the biological and biochemical parameters with respect to physio pathology of trypanosomiasis and their implications in the evaluation of new trypanocidal compounds were discussed. PMID- 1875554 TI - [Thin basement membrane disease in patients with asymptomatic hematuria and/or proteinuria: a clinicopathological study]. AB - To clarify the incidence of thin basement membrane disease (TMD) among the patients with idiopathic asymptomatic hematuria and/or proteinuria, in 217 serious renal biopsies (children 85, adults 132) were studied with clinical and morphometric analysis. TMD used is defined as follows: 1) Glomerulus in minor abnormalities; 2) GBM less than or equal to 200 nm in width, with more than 20% in total glomerular capillary surface; 3) Absence of significant immunoglobulins or complement components. Out of 217 patients 93% had either IgA nephropathy (55%), normal glomeruli (21%) or TMD (17%). TMD consisted of 22% in children and 14% in adults. Remained 15 consisted of non-IgA mesangial proliferative glomerulonephritis (6 cases), incomplete foot process disease (5), membranous nephropathy (2), membranoproliferative glomerulonephritis (1), and unclassified (1). Patients with TMD were found mostly (71%) in younger age less than 20 years old. Out of the patients with TMD, 38% had renal abnormality in the family history, but remainders were sporadic. The common urinary abnormality in TMD was microscopic hematuria occasionally with mild proteinuria (95%), while proteinuria only was rare (5%). Outcome of TMD was favorable prognosis with normal renal function. TMD was histologically divided into 2 groups; diffuse type (GBM thinning was more than 50% in the capillary surface) (19 cases; 51%), and focal type (it was less than 50%) (18 cases; 49%). The incidence of those family history was 64% and 15%, respectively (p less than 0.05). It was concluded that TMD was a popular disorder in patients with asymptomatic hematuria and/or proteinuria and it may expect 17% in incidence. PMID- 1875555 TI - [The mechanisms of exercise-induced proteinuria--relationship between urinary excretion of proteins and lactate after exhaustive exercise]. AB - Exercise-induced proteinuria is of the mixed glomerular-tubular type and has been thought to be due to increased glomerular permeability to macromolecular proteins in response to activation of the renin-angiotensin system and catecholamines and a reduction in renal hemodynamics. The excretion of the tubular type of proteins, however, can't be explained by the above mechanism. Two groups, consisting of subjects with the highest (H-alb, n = 20) and the lowest (L-alb, n = 20) excretion of albumin 30 min after exhaustive exercise were selected from a total of 69 normal male participants. No differences in VO2max, maxHR, changes in plasma angiotensin II, catecholamines, urine volume, or Ccr following exercise were observed between the two groups. The increase in blood lactate concentration immediately after exercise, increases in urinary excretion of lactate, pyruvate, alpha 1 M, beta 2 M, albumin and decrease in Cl- excretion 30 min after exercise in the H-alb group were significantly greater than in the L-alb group. The greater the urinary excretion of lactate and pyruvate, the greater the excretion of albumin, alpha 1M and beta 2M, and the less the urinary excretion of Cl-. The coefficient of correlation between the urinary excretion of lactate and beta 2M was 0.757, and between urinary excretion of albumin and beta 2M, 0.756 (p less than 0.001). These results suggest that exercise-induced organic acids and/or decrease in renal circulatory pH caused by organic acids may alter renal glomerular permeability and inhibit renal tubular reabsorption of low molecular weight proteins (alpha 1M, beta 2M). The permeability of the glomerular basement membrane (GBM) to macromolecular proteins may be altered by a reduction in the charge barrier of the GBM, which may be caused by the over-production of organic acids and a lower pH. PMID- 1875556 TI - [Clinical significance of urinary FDP-E measured by latex photometric immunoassay (LPIA) in the renal disease]. AB - It is well known that urinary FDP is one of the parameters of intrarenal coagulation in renal disease. The measurement of urinary FDP, however, is not satisfactory enough, since it is not a quantitative and sensitive method. Latex photometric immunoassay has recently been developed as a quantitative and more sensitive method. Since fibrinogen reacts with FDP-E less than FDP, the measurement of urinary FDP-E is much better than that of urinary FDP in order to determine the presence of intrarenal coagulation and fibrinolysis of patients with renal diseases. The aim of this study is to clarify the clinical significance of urinary FDP-E measured by LPIA in the renal disease. The results were as follows: (1) Urinary FDP-E correlate with urinary protein, FDP, FDP-D, fibrinopeptide A (FPA), but not serum FDP-E. (2) The diseases which showed higher amounts of urinary FDP-E were diabetic nephropathy, amyloidosis and chronic glomerulonephritis. On the other hand, the diseases which showed smaller amounts of urinary FDP-E were minimal change, toxemia of pregnancy and lupus nephritis. All patients with higher amounts of urinary FDP-E showed marked renal dysfunction. But all the patients with the marked renal dysfunction did not always show higher amounts of urinary FDP-E. The urinary FDP-E showed a positive correlation to 1/serum creatinine. These results suggested that the measurement of urinary FDP-E is a useful method in determining the presence and degree of intrarenal coagulation and fibrinolysis in renal diseases. PMID- 1875557 TI - [Effect of partial nephrectomy on mercuric chloride-induced acute renal failure]. AB - We investigated the effect of partial nephrectomy on mercuric chloride (HgCl2) induced acute renal failure (ARF) in rats. HgCl2 (2 mg/kg) was subcutaneously injected to male Wistar rats 2 days or 2 weeks after either partial nephrectomy or sham surgery. Both deterioration of renal function (serum creatinine, creatinine clearance, and fractional excretion of sodium) and renal tubular damage due to HgCl2-induced ARF were inhibited by 5/6 nephrectomy. A moderate inhibitory effect was also noted by uninephrectomy. The levels of renal tissue ATP and total nucleotide did not increase 12 and 48 hours after uninephrectomy. These results suggest that partial nephrectomy is effective in suppressing the development of HgCl2-induced ARF. The mechanisms of the protection are not explained completely by a consequence of hypertrophy or an acceleration of intracellular energy metabolism. Intrarenal blood flow redistribution may be involved in one of the mechanisms. PMID- 1875558 TI - [Study of tartrate resistant acid phosphatase in patients with chronic renal failure on maintenance hemodialysis]. AB - In the diagnosis of renal osteodystrophy (ROD) and the monitoring of its clinical course, several biochemical parameters have been appreciated as a useful indicators. The present investigations were designed to evaluate the clinical value of serum tartrate resistant acid phosphatase (TRACP) as an additional parameter of osteoclastic activity in ROD based upon the concept that TRACP was marker enzyme specific for osteoclast. Serum TRACP was assayed in 72 patients on long term hemodialysis and compared with conventional parameters of ROD such as ALP, Osteocalcin, Hydroxyproline. Bone change was analyzed according to Jensen's method and categorized into 4 stages. Serum TRACP was exclusively elevated and revealed a evident correlations with each parameters as follows: TRACP v. PTH-C, r = 0.501 p less than 0.01. Hydroxyproline, r = 0.429 p less than 0.05., ALP, r = 0.001., Osteocalcin, r = 0.540 p less than 0.01. In addition, TRACP value in the patients with high stage significantly higher than that in those low stage ROD. These results suggest that measurement of TRACP would be of clinical importance and useful for diagnosis of ROD in chronic maintenance hemodialized patients. PMID- 1875559 TI - [Effect of recombinant human erythropoietin (rEPO) on angina pectoris in patients with chronic maintenance hemodialysis]. AB - We studied the effects of recombinant human erythropoietin (rEPO) on angina pectoris in patients with chronic maintenance hemodialysis. We evaluated hemodynamic changes and exercise tolerance in 6 patients underwent symptom limited treadmill exercise tests, before and 3-months after treatment with rEPO. Hemoglobin concentration and hematocrit increased significantly from 8.1 +/- 1.0 to 10.3 +/- 1.1 g/dl, from 25.7 +/- 2.7 to 31.5 +/- 2.5%, respectively. Exercise duration increased significantly from 291 +/- 68 to 396 +/- 77 sec. Maximal oxygen uptake (VO2max) also increased significantly from 18.3 +/- 3.3 to 24.2 +/- 3.4 ml/kg/min during correction of anemia. Systolic blood pressure (SBP) and pressure rate product (PRP) at rest, and at maximal exercise showed no significant changes, on the other hand ischemic ST change at maximal exercise decreased significantly from 1.2 +/- 0.7 to 0.2 +/- 0.3 mm under 3-months treatment. Our results suggest that improvement of exercise capacity and ST depression in patients with chronic hemodialysis is the outcome of increased coronary oxygen supply with unchanged cardiac oxygen demand after correction of renal anemia treated with rEPO. PMID- 1875560 TI - [Clinical study of renal cell carcinoma as incidental finding]. AB - Reports on renal cell carcinoma (RCC) as an incidental finding have been increasing in recent years as the imaging modalities including ultrasonography (US) and computerized tomography (CT) scan have gained popularity in clinical medicine. Because effective treatment in RCC is only surgical removal of the involved kidney even at present, it is imperative for urologists to find and to diagnose the RCC in early stage. Whether RCC found incidentally is in early stage cancer is not determined at present. To determine if the RCC found incidentally is in early stage cancer and if the survival rate is better than that of the RCC found with symptoms, we undertook the following study. Between December 1972 and March 1990, 65 patients with RCC were registered at the Department of Urology, Teikyo University Hospital. Of 65 patients 20 with RCC as an incidental finding were subjected to this study. 34 patients with RCC found with symptoms including hematuria were subjected to control group. Causes of the diagnosis in 20 patients included workup for non-urological diseases in 11 patients (55.0%), workup for urological disease other than RCC in 5 patients (25.0%) and routine medical checkup in 4 patients (20.0%). First-line imaging modalities for the diagnosis was US in 9 patients (45.0%), DIP in 6 patients (30.0%) and CT in 5 patients (25.0%). Size of the tumor, pathological stage (pT) and grade in these 20 patients were tended to be smaller and lower, respectively, but these results were not significant as compared to those of the control group. Incidence of the remote metastasis, at the time of diagnosis, however, was significantly lesser than that of the control group (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875561 TI - [A case of renal failure due to primary cholesterol atheroembolism]. AB - We report a patient presenting rapid deterioration of renal function due to primary cholesterol atheroembolism. The patient was 75-year-old hypertensive male and was admitted to a hospital because of rt. hemiplegia which developed 2 weeks earlier. On admission, his blood pressure was 200/100 mmHg and serum creatinine level was 2.9 mg/dl with urinalysis 1+ both for protein and hematuria. 2 weeks later, an angiotensin converting enzyme inhibitor (ACE inhibitor, delapril 15 mg/day) was given to control high blood pressure. Immediately after this medication, his renal failure rapidly progressed with a fall in blood pressure (110/60 mmHg) and oliguria (100 ml/day). Although he was transferred to our hospital and was treated with hemodialysis, he died of an attack of acute myocardial infarction in a week. At post-mortem examination, microscopic findings of the kidney disclosed numerous occlusions of medium-sized artery by cholesterol emboli. These emboli were also observed in other organs, but not so prominent as in the kidney. The coronary arteries exhibited severe sclerosis. In this presented case, acute deterioration of renal function was caused by ACE inhibitor, although which was administered in a volume depleted condition. Therefore, further study would be necessary whether or not ACE-inhibitors predispose the patients with this disease to acute renal failure. PMID- 1875562 TI - [Two cases of renovascular hypertension detected by 2-D Doppler method]. AB - Renovascular hypertension is most frequent causes of secondary hypertension. Although angiography of renal artery is reliable procedure for the diagnosis of the renovascular hypertension, it is expensive and invasive. We report two cases which become possible to make diagnosis of the renovascular hypertension by measurement of velocity of segmental or interlobar artery using 2-D color Doppler method. Case 1: 39 year-old male was hospitalized because of hypertension (200/130 mmHg). Ccr was 82 ml/min. 2-D Doppler test demonstrated that the Vmax, the Vmin and the Vmin/Vmax of the right segmental artery were 40 cm/sec., 24 cm/sec. and 0.60, respectively. The Vmax, the Vmin, and the Vmin/Vmax of the left segmental artery were 42 cm/sec., 22 cm/sec. and 0.52, respectively. Renal angiography shows right renovascular stenosis. After percutaneous transluminal angioplasty, the blood pressure became normal and Vmin/Vmax ratio of the right segmental artery was down to 0.52. Case 2: 46 year-old male was hospitalized because of chronic renal failure (Ccr: 14.6 ml/min) and uncontrollable hypertension. 2-D Doppler test demonstrated that the Vmax, the Vmin, the Vmin/Vmax ratio and the acceleration of the right segmental artery were 10 cm/sec., 6 cm/sec., 0.62 and 1.7 m/sec.2, respectively. The Vmax, the Vmin, the Vmin/Vmax ratio and the acceleration of the left interlobar artery were 8 cm/sec., 5 cm/sec., 0.63 and 0.8 m/sec.2, respectively. Renal angiography shows bilateral renovascular stenosis. Thus, the elevated value of Vmin/Vmax ratio (over 0.6) (mean value: 0.43 +/- 0.08, when Ccr is over 70 ml/min, whereas 0.32 +/- 0.11, when Ccr is under 30 ml/min) and decreased acceleration (under 2.0 m/sec. 2) of the segmental or the interlobar artery seems to be helpful for the diagnosis of renovascular hypertension. PMID- 1875563 TI - [Two cases of nephrotic syndrome associated with hydronephrosis]. AB - We reported two cases of nephrotic syndrome associated with hydronephrosis. A forty four year old male patient who suddenly complained of nephrotic syndrome, showed left hydronephrosis caused by lower ureteral stenosis. Renal biopsy specimen obtained from the right kidney revealed minor glomerular abnormalities. A sixteen year old female patient had a long history of proteinuria before the onset of nephrotic syndrome. She suffered from bilateral hydronephrosis of which the etiology was unclear. Renal biopsy specimen obtained from the left kidney revealed membranous nephropathy. Because in both cases urine samples collected from each ureter showed the presence of a massive protein, the other kidney was thought to be involved with the same disease. The association of nephrotic syndrome with hydronephrosis is extremely rare. The significance of this unusual combination was discussed with respect to the literature. PMID- 1875564 TI - [A case of iron and aluminum related osteomalacia in a long-term hemodialysis patient]. AB - A 32-year-old woman undergoing hemodialysis for 12 years was referred because of systemic bone pain and pathological fracture of ribs and right tibia. Her serum ferritin was 4800 ng/ml, liver CT level was extremely high and skeletal scintigram by 99 m-Tc-MDP revealed high activity of soft tissue. Her serum aluminum was elevated more than 20 micrograms/dl by deferoxamine infusion test. Osteomalacia and positive staining of both aluminum and iron was observed by bone biopsy examination. After treatment with deferoxamine as a chelating agent of iron and aluminum, bone pain was relieved and second bone biopsy specimen revealed improvement of osteomalacia. But serum aluminum was slightly reduced and serum ferritin level and liver CT level were unchanged. PMID- 1875565 TI - [Experimental bladder tumor]. AB - Experimental bladder tumor was reviewed in this paper. Many investigators have been studying on the bladder carcinogenesis since occupational bladder cancers were reported. Main object in research for bladder cancer was to identify and remove environmental causes and various factors related to the development of bladder cancer. Human bladder cancers can be classified into papillary non invasive and nodular invasive cancer. The establishment of an animal model of bladder cancer similar to human bladder cancer is important to clarify the natural history of this disease and obtain basic data on its clinical diagnosis and treatment. Bladder carcinogenesis has been known to occur in a two-stage process: initiation and promotion. Recently inhibitory effects on the bladder carcinogenesis were also studied. In this paper we described the results that have been obtained in our laboratory concerning animal bladder carcinomas. PMID- 1875566 TI - [Effect of biological response modifiers on a spontaneous murine renal cell carcinoma regression of metastases caused by the streptococcal preparation OK 432]. AB - The effect of the streptococcal preparation OK-432, which is one of the biological response modifiers, was examined in BALB/c mice using a transplantable murine renal cell carcinoma (Renca) of spontaneous origin, and an analysis of effector cells was performed. The tumor grew progressively and metastasized consistently to the abdominal lymph nodes and then to distant organs following the inoculation of Renca cells in the left renal subcapsular site in BALB/c mice, and the survival time of the mice was under 42 days. In this tumor model, i.p. administration of OK-432 after tumor inoculation significantly extended the survival time and significantly inhibited the formation of the inoculated tumor itself. Removal of the left kidney on the 7th day after tumor inoculation neither extended the survival time nor augmented the effect of OK-432. Splenic cells obtained on the 7th day after tumor inoculation from Renca-bearing mice treated with OK-432 were capable of lysing syngeneic Renca cells, NK-sensitive allogenic YAC-1 cells, and LAK-sensitive EL-4 cells in a 4-hour 51Cr-release assay in vitro. Those obtained from healthy mice treated with OK-432 also showed cytotoxic activity against Renca cells. The cytotoxicity of splenic cells from Renca bearing mice treated with OK-432 was lost almost completely for both Renca and YAC-1 cells after in vitro treatment with anti-asialo GM1 antibody, and was partially lost after in vitro treatment with anti-Thy-1,2 antibody. Additionally, in vivo i.p. administration of anti-asialo GM1 antibody significantly counteracted the effect of OK-432 on survival. These findings demonstrated that Renca cells were NK-sensitive and that the i.p. administration of OK-432 was beneficial for the prevention of the spontaneous metastasis of Renca carcinoma. As the effectors, NK cells played a dominant role and activated T cells were also involved. PMID- 1875567 TI - [Histological and immunohistochemical studies on the damage of contralateral testis following the unilateral testicular torsion in Wistar rats]. AB - The effect of experimental unilateral torsion of the testis on the contralateral intrascrotal testis in Wistar rats was evaluated histologically and immunohistochemically. The results were summarized as follows. 1) Histological damage of the seminiferous tubules in the contralateral testis was present only in adult rats. 2) The histological change 3-5 weeks after the experimental torsion consisted of marked decrease of spermatocytes, loss of spermatids and spermatozoa and numerous Sertoli-cell only tubules. Hyperplasia of the interstitial cells was demonstrated without thickness of the basement membrane and infiltration of the inflammatory cells. The tubular diameter and the ratio of contralateral testicular weight to rat body weight were significantly decreased (p less than 0.05) in torsion group. 3) Using an indirect immunofluorescent method, the positive immunohistochemical staining on spermatid and spermatozoa of normal testicular tissue was demonstrated using only the serum of rat with histological damage on the contralateral testis. Therefore, the phenomenon may be ascribable to the presence of antisperm antibody. It is concluded that the mechanism of the damage in seminiferous tubules of the contralateral testis with experimental torsion in adult Wistar rats is related to the humoral immunity producing antisperm antibody. PMID- 1875568 TI - [Clinical course of bone metastases by prostatic cancer studies with conventional X-ray]. AB - The clinical courses of bone metastases in 81 cases of prostatic cancer were examined using conventional X-ray. All patients received endocrine therapy as the initial treatment; castration and estrogen were given to 46 cases, castration and antiandrogen to 19, LH-RH analog to 11, flutamide to 5. The response to endocrine therapy was evaluated every 6 months after the start of the treatment according to National Prostatic Cancer Project criteria. The prognosis was calculated by cause-specific survival. The types of untreated bone metastases on X-ray were classified into five: sclerotic in 12 cases (15%), mixed but mainly sclerotic in 25 (31%), mixed but mainly lytic in 14 (17%), lytic in 8 (10%) and undetermined with positive scintigraphy in 22 (27%). Two mixed types showed more spread metastases and tendency of elevated prostatic acid phosphatase when compared with other types. Temporary enlargement of sclerotic area within 6 months after start of the treatment did not correlate with deterioration of disease. Remodeling of metastatic areas occurred 6-36 months after start of the treatment showed curative course and the prognosis of these groups were favorable. Most of lytic areas tended to sclerotic finding following endocrine therapy regardless of effects by endocrine therapy. Sclerotic and two mixed types showed better and worse tendencies, respectively. On viewpoint of remodeling, change of metastatic area and newly appearance of metastases, an evaluation criteria of response to the therapy was proposed, which showed good correlation with prognosis. From these observations, it was concluded that bone metastases tended from lytic to sclerotic changes and that lytic-sclerotic cycles occurred repeatedly along with disease progression regardless of effect to therapy. Remodeling seemed to be curative signs of metastatic area. PMID- 1875569 TI - [Endourological re-establishment by transluminal puncture for a complete obliteration of traumatic urethral disruption]. AB - We performed transluminal re-canalization by needle puncture under fluoro endoscopic control on a total of ten patients (membranous urethra, 8; bulbous urethra, 2) with complete obliteration after traumatic urethral disruption. The re-canalized tract was created by balloon dilation, internal urethrotomy or endoscopic resection of the scar tissue. The patient age ranged from 10 to 57 years (mean age; 37.9 +/- 15.3 years). A transluminal puncture was attempted in three patients by transperineal-transurethral approach and in seven by transurethral approach. In one of them, who sustained a complete membranous disruption 5 weeks ago, transluminal puncture failed because of the movable proximal urethra. The remaining nine patients voided without difficulty for the mean follow-up period of 18.1 +/- 14.3 months (range: 2-46). Three patients had mild stress urinary incontinence. A transluminal puncture is less invasive, safe and reliable for re-establishment of the true proximal part of the disrupted urethra. It can be recommended as a useful technique for endo-urological re establishment for a completely obliterated urethra. Although this endoscopic re establishment requires urethral sounding or internal urethrotomy for 6 months postoperatively, it may be an alternative to conventional surgical repair. PMID- 1875570 TI - [Studies on pulmonary metastasis of renal cell carcinoma--pulmonary embolism revealed by lung-perfusion imaging and metastasis]. AB - Invasion of renal cell carcinoma to veins is known to have a close relation with pulmonary metastasis. We speculated that a tumor thrombus would lodge in the pulmonary artery before establishment of a clinically apparent pulmonary metastasis. This may be particularly true in patients with renal vein or vena cava involvement of renal cell carcinoma. In this instance, it is crucial to know the clinical consequence of tumor thrombi in the pulmonary artery. Thus, we investigated these issues with the aid of lung-perfusion imaging in 22 renal cell carcinoma patients with and without vein involvement. The lung-perfusion imaging revealed positive in 8 of the patients examined prior to treatment. The incidence of positive finding was well correlated with an extensive vein invasion. Patients with positive imaging prior to treatment were associated with pulmonary metastasis at a higher rate than those with negative findings. These findings have indicated that vein invasion should be related with tumor thrombus formation in the pulmonary artery, and such a status in the lung would, in part, result in pulmonary metastasis. Two different clinical courses were found by an analysis of patients with the positive imaging prior to treatment. One is the clinical course in which positive findings were correlated with a newly developed metastasis in the lung. Thus, care should be taken in development of the metastasis during the follow-up when patients show the positive lung-perfusion imaging prior to treatment. On the other hand, we found two patients in whom the positive findings disappeared during the follow-up. PMID- 1875571 TI - [Vesicoureteral reflux and renal scarring. Report of cooperative study of "Progressive renal disease" of Ministry of Health and Welfare]. AB - 196 cases with vesicoureteral reflux (VUR) from multiple centers were analysed to examine the relationship between VUR and reflux nephropathy. The high correlation (p less than 0.01) was observed between reflux and renal scarring. Even in cases in whom VUR was not demonstrated at the time of testing, renal scarring of various degrees was recognized, suggesting either co-existed hypoplastic kidney or pre-existed infection. The renal scarring, but not VUR, had a significant correlation with proteinuria and hypertension. Retrospective analysis shows that the surgical treatment was closely related to the degree of renal scarring but not to the degree of reflux. Renal scarring progressed even when reflux did not become worse, which is probably accounted for by the presence of pyelonephritis. Although frequency of pyelonephritis decreased significantly (p less than 0.01) from 0.60 +/- 0.89 to 0.084 +/- 0.305 times/patient. year after anti-reflux surgery, renal scarring progressed in 13 kidneys (5.8%). Seven of the 13 kidneys became worse due to the surgical failure. The scar progression was recognized in the remaining six kidneys (three patients) including adult cases despite the successful surgical correction of reflux. Our study points to the urged need for a prospective clinical trial designed for the study of the pathological and clinical background of progressive renal failure in VUR. PMID- 1875572 TI - [Clinical efficacy of modified M-VAC chemotherapy for advanced urothelial carcinoma and influence of squamous cell carcinoma-associated antigen on efficacy of the chemotherapy]. AB - The efficacy of modified M-VAC chemotherapy was evaluated in twenty-two patients with advanced urothelial carcinoma (18 cases of transitional cell carcinoma, 3 of transitional cell associated with squamous cell carcinoma and 1 of squamous cell carcinoma). Among the 22 patients, 14 underwent two or more courses of modified M VAC chemotherapy and had lesions suitable for the evaluation. Three of the 14 patients achieved complete response and 6 partial response, resulting in a 64.3% response rate. With regard to the direct effect according to the site of the lesion, the response rate was 75% for the urinary bladder, 100% for lung, 100% for subcutaneous tissues, and 75% for lymph nodes metastasis, whereas the chemotherapy was ineffective for metastasis in the bone and muscle. With this neoadjuvant chemotherapy the primary tumor of the urinary bladder was downstaged from T2 to T0 in one patient who showed complete response. In 4 of 5 patients achieving partial response, the primary tumors were downstaged from T2 to T1. Of 9 patients given this chemotherapy for metastatic lesions, 2 achieved complete response and are alive, whereas all 3 without response died of cancer within the 1 year following the chemotherapy. Since most of the cases associated with the squamous cells carcinoma component showed no response to the therapy, it seems that the level of serum squamous cell carcinoma-associated antigen may be helpful for predicting the efficacy of modified M-VAC chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875573 TI - [Studies on calcium oxalate crystal formation in urolithiasis. Multi-regressive analysis of urinary CaOx crystalline volumes and the effects of urinary various substances on CaOx crystal formation]. AB - Because human urine contains various substances which can affect each other, it is quite difficult to clarify the mechanism of formation of calcium oxalate (CaOx) crystal in urine. The authors recently determined CaOx crystalline content and the concentrations of other substances in urine specimens from patients with urolithiasis and healthy volunteers, and subjected the data to multi-regressive analysis for the purpose of assessing the effect of these urinary substances on CaOx crystal formation. 1. In analysis of urine from patients with urolithiasis, the partial correlation coefficients of CaOx crystal formation with oxalic acid, sodium, calcium, uric acid magnesium were 0.67, 0.28, 0.18, and -0.10, respectively. The formula of regression was as follows: Amount of CaOx crystal (X 10(6) microns3/ml) = 3.59 X 10(-2) Ox (mM/L) + 4.72 X 10(-3) Ca (mM/L) + 4.52 X 10(-3) Na (mM/L) + 2.51 X 10(-4) UA (mM/L) -2.39 X 10(-2) Mg (mM/L) -1.65. The multiple correlation coefficient was 0.759. Thus, in patients with urolithiasis, urinary crystal formation was most dependent on the oxalic acid level, sodium, calcium, and uric acid were found to promote crystal formation, while magnesium to suppress it. 2. In analysis of urine from healthy volunteers, the partial correlation coefficients of CaOx crystal formation with oxalic acid and inorganic phosphorus were 0.51 and -0.24, respectively. The formula of regression was as follows: Amount of CaOx crystal (X 10(6) microns3/ml) = 1.91 X 10(-2) Ox (mM/L) 3.43 X 10(-4) P (mM/L) +0.29 The multiple correlation coefficient was 0.525.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875574 TI - [Macroscopic tumor thrombus in renal cell carcinoma]. AB - Prognosis of 114 patients treated for renal cell carcinoma from 1972 to 1988 was investigated to evaluate intravenous tumor extension as a prognostic factor. Those in whom presence or absence of macroscopic tumor thrombus was not confirmed were not included in the current patient group. Tumor stages were evaluated according to TNM criteria except that intravenous tumor thrombus was not counted for local staging. Incidence of T3 and T4 tumors, distant metastasis and grade 3 anaplasia (G3) were higher in V+ group (V1 + V2) than in V0 group, which appeared to be a major difference of background making 5-year actuarial survival rates in V1 and V2 patient groups worse than in V0. Therefore, 5-year actuarial survival rates in N0 and M0 cases receiving radical nephrectomy were compared and found 83.3% in V2 group, 54.4% in V1 and 87.3% in V0. Since V1 group included G3 tumors more frequently than the other two groups, 5-year survival rates were further compared after excluding those with G3 tumors and found to be identical among V0, V1 and V2 groups. The current results indicate that macroscopic intravenous extension of renal cell carcinoma is an accompanied phenomenon secondary to high grade and invasive tumors and therefore, not a primary risk factor for prognosis. Accordingly, it is questionable to regard macroscopic tumor thrombus itself as a risk factor for clinical staging. PMID- 1875575 TI - [The evaluation of cystoscopy in the screening of asymptomatic microhematuria]. AB - As a prospective study on asymptomatic microhematuria, complete urological examinations including cystoscopy, IVP, ultrasound and urinary cytology were performed on 422 patients over 40 years old between January 1987 and December 1988 (group A). The results of group A was compared with that of retrospective study on 266 patients, who had incomplete urological examination between January 1984 and December 1985 (group B). Cystoscopy was performed on 321 patients (87.2%) in group A and on 108 patients (40.6%) in group B. Bladder tumor was found in 10 cases (2.4%) in group A, including 7 cases of male patients (5.7%), but in only 1 case (0.4%) in group B. Since the negative rate of abnormal urinary cytology was 50% and that of abnormal IVP was 90% in 10 cases of bladder tumor in group A, cystoscopy was considered to be an essential examination for the screening of patients with asymptomatic microhematuria over 40 years old patients. PMID- 1875576 TI - [Regional lymphadenectomy for renal pelvic and ureteral cancers]. AB - Thirty-four patients with renal pelvic and ureteral cancers received regional lymphadenectomy since 1980. The patients consisted of 21 with renal pelvic cancers, 10 with ureteral and 3 with renal pelvic and ipsilateral ureteral. Fifteen patients (44.1%) had metastatic nodes: 13 with renal hilar or para-aortic metastases and 2 with pelvic nodal involvements only. Thirteen of these 15 patients with nodal metastasis had high grade tumors and 14 had high stage tumors. The 5-year survival rate of these 15 patients was 26.3% which was considerably poor when compared with 19 patients without metastasis. Twenty patients with high grade and high stage tumors who received respective operations with regional lymphadenectomy had significantly better prognosis compared with the historical control group (15 patients, from 1961 to 1979). Additional regional lymphadenectomy for renal pelvic and ureteral cancers appears to be a valuable operation for improving prognosis. PMID- 1875577 TI - [Treatment of malignant pheochromocytoma by combination of CVD regimen and transarterial embolization]. AB - We performed combination therapy with cyclophosphamide, Vincristine and Dacarbazine (CVD) regimen and transarterial embolization (TAE) in 2 cases of malignant pheochromocytoma with metastases. Case 1: 59-year-old female. After primary left adrenal lesion had been removed, recurrence at the left renal hilar region and metastases to the right iliac bone and 5th cervical vertebra occurred. We took 3 courses of CVD regimen after TAE for the lesions in the right iliac bone. Her endocrinological data has been normal for more than 1 year after treatment. Case 2: 29-year-old male. Total cystectomy, ileal conduit and pelvic lymphadenectomy had been performed for the primary lesion of the urinary bladder. 2 years after the 1st operation, metastases to the right obturator nodes and multiple bones occurred. We gave 3 courses of CVD regimen followed by TAE for the lesions in the right obturator nodes. Just after treatment, we could stop insulin and reduce anti-hypertension drugs, but the effect of treatment was temporary. In conclusion, combination of CVD regimen and TAE is effective for malignant pheochromocytoma with metastases. PMID- 1875579 TI - Kansas Medical Society membership directory, 1991. PMID- 1875578 TI - Unicompartmental knee arthroplasty. PMID- 1875580 TI - [Chemotherapeutic regimens that were considered effective to cure pulmonary infection caused by Mycobacterium avium-Mycobacterium intracellulare complex]. AB - During the period of 24 years from 1965 to 1988, we treated a total of 181 patients who had pulmonary infection caused by Mycobacterium avium--Mycobacterium intracellulare complex (MAI complex). Of these 181, 34 (19%) were cured showing sputum conversion and disappearance of cavity or marked reduction of cavity in the size to 1/2 or less or change of the cavity to thin-walled one. In these patients, negative culture continued at least for one year by monthly sputum examination. The most frequently used regimen in these patients was RFP + INH + SM, and the secondly RFP + INH + EVM, and thereafter multiple drug regimens including RFP + INH. The most frequently used drugs were RFP, INH, EVM, SM and EB. Based on the above results, we recommend the regimen RFP + INH + EVM + EB or RFP + INH + SM + EB, to which, if possible, were added a combination of MC + SX + KT. (As to abbreviations, refer to Table 3). PMID- 1875581 TI - [Primary operation of pericardiectomy and decortication of the right lung for tuberculous pericarditis with empyema]. AB - A 28-year old man who complained of ortho-apnea and fever was diagnosed to have cardiac tamponade. Pericardiocentesis was immediately carried out and peri cardiac window was created on the 11th day. Typical caseating granulomas with acid-fast bacilli were detected in sections of the pericardium. A positive culture of Mycobacterium tuberculosis was observed in the sputum and the pericardial fluid. Though 3-month anti-tuberculosis treatment with streptomycin, isoniazid, and rifampicin was continued with 6-week steroid therapy, progressive thickness of the pericardium was suggested subsequent constriction. Pericardiectomy for pericarditis and decortication for empyema in the right thorax was performed at the same time. After 10 x 12 cm pericardium was resected through median sternotomy, decortication of the right lung was performed through right posterolateral thoracotomy. In the case with thickened pericardium, early pericardiectomy is recommended. PMID- 1875582 TI - [A case of pleuritis tuberculosa which was diagnosed as inoculated tuberculosis after 43 years]. AB - In May, 1946, one hundred two children were detected to have inoculated tuberculosis on their arms among the primary school children in Hyogo prefecture who had received anti-typhoid vaccine on the same spot. Of the 102 patients in the past 25 years, 26 (25%) developed secondary tuberculosis. One of these inoculated tuberculosis patients, 53-years-old woman, was admitted for pleuritis tuberculosa in September, 1989. She had not been included in secondary tuberculosis group. The relationship between her past inoculated tuberculosis and the pleurisy has not been proved. However, this pleurisy would have been developed in case it was caused by the past tuberculosis after 43 years. PMID- 1875584 TI - Update on the Alzheimer's Association. PMID- 1875583 TI - Recognizing alcohol abuse in the elderly. PMID- 1875585 TI - AGEWELL: a nursing directed program. PMID- 1875586 TI - My friend Beth age 92. PMID- 1875587 TI - [Various aspects of the anti-aggregatory action of diltiazem and cordaphene in patients with ischemic heart disease]. AB - Some aspects of the antiaggregatory action of calcium antagonists were studied in 50 patients with stable angina pectoris. Dilzem (diltiazem) and cordaphene (nifedipine) were tested for their effects on the erythrocytic component of hemostasis, taking into account their capability of suppressing hemolysis, which made ADP, an important thrombocytic activator, enter the blood flow. The two agents significantly reduce the concentration of plasma ADP, free hemoglobin, diminish mechanical erythrocytic resistance, and block platelet aggregation to a varying degree. A relationship was established between the levels of blood nifedipine and the magnitude of rheological effects. With this, the patients with coronary heart disease showed a good antianginal effect. PMID- 1875588 TI - [Characteristics of nicardipine treatment of patients with ischemic heart disease]. AB - The new calcium antagonist nicardipine (barizine) was tested for effects on platelet function and transient myocardial ischemia in 23 patients with coronary heart disease. Prior to the therapy, lower platelet function was more frequently encountered in patients with more severe angina pectoris and more prolonged myocardial ischemia. The efficacy of nicardipine was demonstrated to be related to the clinical course of coronary heart disease and the baseline platelet function. It is advisable to prescribe the drug to patients with Functional Class II stable angina and higher platelet functional activity. PMID- 1875589 TI - [Effect of xanthinol niacinate on the autoimmunity and capillary permeability in patients with stable stenocardia]. AB - A three-month antianginal therapy with long-acting nitrates and xanthinol nicotinate given in various daily doses have shown that there is a positive clinical effect, a reduction in the level of immune complexes and IgG in most patients, which is followed by a decrease in capillary permeability and dienic conjugate levels both in erythrocytes and plasma. PMID- 1875591 TI - [Prognostic significance of "silent" myocardial ischemia in patients with unstable stenocardia]. AB - A 24-hour ECG monitoring was performed in 30 patients with unstable angina. Ten patients had episodes of transient ST-segment displacement only in the presence of anginal attacks (Group 1), 10 had ST-segment displacement episodes in the presence of both anginal attacks and silent myocardial ischemia (Group 2), and 10 with the displacements concurrent with only silent ischemia (Group 3). The patients from the groups were not significantly different in terms of major clinical, history, and angiographic data. Following an average of 1 year, death and acute myocardial infarction were observed in 1 (10%) and 2 (22.2%) in Group 1; 1 (10%) and 3 (33.3%) in Group 2; and 2 (20%) and 5 (62.5%) patients, respectively. It was concluded that episodes of silent myocardial ischemia are prognostically more hazardous than those of transient hypoxic ECG changes concomitant with anginal attacks. PMID- 1875590 TI - [Contractile function of the myocardium in patients with ischemic heart disease after aortocoronary bypass]. AB - Fifty patients with coronary heart disease underwent repeated coronary ventriculography in different periods after aortocoronary bypass. The myocardial contractility in the patients after direct myocardial revascularization was comparatively analyzed in relation to the function of imposed aortocoronary anastomoses. Myocardial segmental contractility considerably improved in 23 patients after aortocoronary bypass who had functioning shunts, the integral function being satisfactory within the whole follow-up, whereas left ventricular myocardial function progressively diminished in 27 patients with closed anastomoses. Progressive coronary bed atherosclerosis was found to have a noticeable effect on myocardial contractility. PMID- 1875592 TI - [Selection of the optimal criteria of evaluation of the results of spiroergometry in patients with ischemic heart disease]. PMID- 1875593 TI - [Modeling the effectiveness of the rehabilitation treatment of patients in the post-infarction period]. AB - A two-year follow-up of 400 patients with prior myocardial infarction and usage of regression and discriminant analysis algorithms provided a number of linear models to predict changes in the patients' working capacity over the observed period. A variety of models depending on the feasibility of a laboratory to apply instrumental tools for examination suggested their wide utilization. The advantage of the models is that a small set of signs is used, no computer engineering is required. The models may be used in patients with different clinical disease (uncomplicated, repeated or cardiac aneurysm-complicated myocardial infarction). The modelling provided accurate prediction at 84-100% levels. PMID- 1875594 TI - [Possibilities of the questionnaire method for detection of the symptoms of preclinical stages of coronary arteriosclerosis and ischemic heart disease]. AB - A comprehensive study was made of 140 males aged 26-55 years who were divided into 3 groups: (1) 47 healthy individuals; (2) 67 subjects with early signs of coronary heart disease; and (3) 29 patients with coronary heart disease (Functional Class II). The pattern of chest pain was thoroughly analyzed by a specially developed questionnaire. The results were compared with the data obtained from an interview by Rose's questionnaire. The analysis demonstrated that neither Rose's questionnaire nor the detailed one specially developed by the authors identified subjects with preclinical coronary heart disease. PMID- 1875595 TI - [Electrophysiological mechanisms of the effect of allapinin in patients with paroxysmal supraventricular tachycardia]. AB - An intracardiac electrophysiological study was undertaken to examine 15 patients with paroxysmal supraventricular tachycardias. Allapinin intravenously given in a dose of 0.4 mg/kg, was tested for effects. The agent was demonstrated to cause a substantial inhibition of rapid retrograde pathway function in atrioventricular nodal tachycardia and abnormal antero- and retrograde pathway function. This is the major aspect of the drug's action that prevents the development of episodes of paroxysmal supraventricular tachycardias. The agent fails to virtually affect the function of the atrioventricular node in the anterograde direction in the two types of the tachycardia. Thus, allapinin has the mechanism of action that is typical of quinidine-like drugs used in supraventricular tachycardias. PMID- 1875596 TI - [Evaluation of the possibility of selection of individual anti-arrhythmia therapy]. AB - Antiarrhythmic therapy was chosen for 3-7 days by modified chronic electrophysiological study at three stages: (1) the efficacy of a drug, its action onset and termination were defined; (2) a dosage was chosen on an individual basis and the duration of drug potency was specified; (3) the dosage regimen of a drug given as a course therapy was confirmed by the results of trials. Its choice was made on the basis of the oral administration of a tested drug and multiple programmed electric cardiostimulation. In late periods (3-37 months), the therapy was effective and safe in 51 (86%) of 59 patients. The drug regimens and doses were in poor agreement with conventional ones in 49% of the patients. The method proposed makes it possible to choose antiarrhythmic therapy on an individual basis and reduce the number of complications. PMID- 1875597 TI - [Spontaneous restoration of cardiac rhythm in patients with a persistent form of atrial fibrillation]. AB - A total of 15 patients with spontaneously arrested sustained atrial fibrillation (its duration 7.0 +/- 1.6 years) were followed up. After termination of atrial fibrillation, all the patients had signs of the sick sinus syndrome (profound sinus bradycardia, pacemaker migration, inferior atrial and atrioventricular rhythms). Thirteen of 15 patients suffered from rheumatic heart disease, nine of them had severe heart failure. Four patients immediately died. An atrial fibrillation relapse occurred in the immediate period in most cases, and rhythm recovery was unaccompanied by the improvement of the patients' condition. PMID- 1875598 TI - [Use of dietary fish oil--an alternative to drug therapy of dyslipidemia]. AB - The clinical efficacy of "Food ichthyenic oil", a new foodstuff, was studied in 129 patients with atherogenic dyslipidemia. The oil was given in a daily dose of 30 ml which contained 8 g polyunsaturated fatty acids of the omega-3 class. All the patients were divided into 3 groups: (1) 44 patients with 5.2-6.5 mmol/l cholesterol; (2) 37 with over 6.5 mmol/l, and (3) 48 with hypercholesterolemia (cholesterol over 5.2 mmol/l and hypertriglyceridemia (triglycerides over 2.3 mmol/l). Following 1-month therapy, all the groups displayed lower low density lipoprotein cholesterol levels and significantly higher high density lipoprotein cholesterol concentrations. After 4-month intake of ichthyenic oil, the levels of total and LDL cholesterol returned to the baseline values, whereas the concentration of HDL cholesterol was significantly higher than the baseline one. Following 12-month therapy, there were 15 and 14% decreases in total and LDL cholesterol, respectively, a 16% increase in HDL cholesterol. The patients from Group 3 exhibited low VLDL cholesterol and triglyceride levels. PMID- 1875599 TI - [Use of Doppler echocardiography for studying hemodynamics in paroxysmal supraventricular tachycardia]. AB - Eighteen patients in whom sustained supraventricular tachycardia paroxysms were induced by programmed transesophageal pacing were examined. Doppler echocardiography was used to study left ventricular systolic and diastolic function, as well as cardiac output and pulmonary systolic pressure during sinus rhythm and paroxysms. A profound decrease in the cardiac index during paroxysms was found in 2 patients, one of them had higher pulmonary pressure. The cardiac index increased on an average from 4.4 +/- 0.9 l/min.m-2 during sinus rhythm to 4.8 +/- 1.4 l/min.m-2 during paroxysms. The diastolic function of the left ventricle was ascertained to be one of he factors that determine cardiac index in supraventricular tachycardia paroxysms. PMID- 1875600 TI - [The role of genetic factors in determining the ECG indicators]. AB - ECG parameters were examined in 62 families with a history of arterial hypertension. A genetical-and-dispersion analysis of ECG parameters were made. There was a high genetic determination with X-chromosomal effect, R-R interval duration, and Makruse index values. A high degree of inheritance of P-Q interval duration, left ventricular activation time and R wave height in the lead V6 was ascertained. The household more frequently displayed the early ventricular repolarization syndrome and the partial preexcitation syndrome. There was a genetic determination of these electrocardiographic phenomena. The findings provide evidence for the fact that search for genetic markers of arterial hypertension among ECG parameters seems to be promising. PMID- 1875601 TI - [Value of isometric and dynamic exercise tests with standard drug doses for selecting long-term antihypertensive treatment with vasodilators, adrenergic beta blockaders and diuretics]. AB - The paper presents the results of the study into the efficacy of single routine doses of essential antihypertensive agents (nifedipine, propranolol, and hydrochlorothiazide) versus its course treatment at rest and during isometric and dynamic exercise tests. The efficacy was assessed by using the Dixon criterion. The routine drug dose tests performed at rest and during isometric and dynamic exercise were shown to have a varying informative value in the prediction of long term treatment with the above drugs. The isometric and dynamic exercise tests are of the greatest significance in the evaluation of the antihypertensive routine dose of nifedipine, whereas the dynamic exercise test alone is of value for propranolol and the rest exercise test, the both exercise tests for hydrochlorothiazide. Thus, the results of the corresponding routine drug dose tests are of varying predictive informative value, which is essential both for choosing an effective drug and for making an objective assessment of the outcomes of the course therapy. PMID- 1875602 TI - [Pulmonary hemodynamics in patients with hypertension during acute drug tests using obsidan and corinfar]. AB - Two-dimensional and Doppler echocardiographies were used to examine 102 hypertensive patients who were found to have pulmonary hypertension, whose manifestation was determined by the degree of arterial hypertension, cardiac contractile insufficiency and diminished left heart pump function. The degree of pulmonary hypertension was related to the hemodynamic type and maximal with hypokinetic circulation when the pump function of the heart was minimal. Obsidan caused a decrease in pulmonary and systemic arterial hypertension, producing higher effects with hypokinetic hemodynamics. Corinfar was demonstrated to attenuate pulmonary hypertension to a greater extent. Its action on systemic arterial hypertension was highest in patients with hyperkinetic circulation. Heterodirectional hemodynamic effects of these drugs make it expedient to study their combined action on the hemodynamic of hypertensive patients. PMID- 1875603 TI - [Predicting the volume and hemodynamic outcome of radical correction of tetralogy of Fallot on the basis of angio- morphometry]. AB - Using the findings from angiographic examination of 91 patients with Fallot's tetrad, the authors developed an angiomorphometric protocol which may predict the feasibility of radical correction of the defect prior to an operation and hemodynamic parameters in the immediate postoperative period, peak right/left ventricular systolic pressure ratios, in particular. The reasons for discrepancy of estimated and measured right/left ventricular systolic pressure ratios were defined and their time course was followed up 12 hours after radical Fallot's tetrad correction in relation to the type of plastic operations. PMID- 1875604 TI - [Electrodestruction of the atrioventricular junction in a patient with post infarction ventricular tachycardia]. PMID- 1875605 TI - [The first experience with clinical use of ultrahigh frequency electric current for destruction of the atrioventricular junction]. PMID- 1875607 TI - [Use of biofeedback in the treatment of arterial hypertension]. PMID- 1875606 TI - [Release of myocardial enzymes after ablation of the bundle of His]. PMID- 1875608 TI - [The mutual aggravation syndrome in pancreatic cancer and diabetes mellitus]. AB - Examined were 27 patients with pancreatic cancer and concomitant diabetes mellitus. It was established that in women, the likelihood of pancreatic cancer development increases with the age. Obesity and cholelithiasis are also the risk factors for development of cancer of the given location. In pancreatic cancer and diabetes mellitus lasting more than 2 years which is an independent disease with a tumor developed against its background, the mutual aggravation syndrome occurs: a severe course of diabetes and increased growth of a neoplasm. PMID- 1875609 TI - [Prevention of suppurative-infectious complications after radical surgery in rectal cancer]. AB - In 32 patients with rectal cancer, the endolymphatic antibiotic therapy was performed 2-5 days before and for 7-10 days after radical operation. Attenuation of an inflammation around a tumor, decrease in bacterial contamination of the perineal wound, reduction in incidence of postoperative purulent-inflammatory complications were noted. PMID- 1875610 TI - [Acute hepatorenal failure as a component of multiorgan failure syndrome in patients after surgical intervention]. AB - The etiology, pathogenesis, clinical features of acute postoperative hepatorenal failure (APHRF) in 50 surgical patients were studied. APHRF was considered as a component of the multiorgan insufficiency syndrome. The general somatic factors contributing to APHRF development were established: chronic pathology of the liver and kidneys, chronic cardiogenic pathology, hypertension. The risk factors for APHRF development before, at operation and at the nearest period after it were distinguished: shock, hemorrhage, massive transfusion of blood, or its components, hypoxia, systemic arterial hypotension. The attention is attracted to the significance of combination of the systemic arterial hypotension with the contributing general somatic factors and risk factors before, at operation and at the nearest period after it in APHRF development. PMID- 1875611 TI - [Several problems of surgical treatment in acute biliary pancreatitis]. AB - The authors used in 39 patients with the intact gallbladder and after previously performed cholecystectomy the therapeutical tactics developed on the basis of consideration of the peculiarities of clinical course of acute biliary pancreatitis, and as well the original methods of treatment (auriculotherapy, selective hepatic vagotomy). This permitted to achieve the reduction in incidence of complications down to 11.5%, lethality--to 2.8%. PMID- 1875612 TI - [Use of Soviet fibrin adhesive in liver surgery in experimental animals]. AB - The results of a comparative experiment for studying the native glue composition on a fibrin base, which possesses the hemostatic and adhesive properties and has the influence on the processes of regeneration, and modern synthetic medical glues are presented. The essential advantages of a fibrin-based glue were revealed. PMID- 1875613 TI - [Results of surgical treatment of bleeding gastric tumors]. AB - The results of surgical treatment of 132 patients with gastric tumors complicated by bleeding are presented. In 58.4% of the patients, the radical intervention was performed, in uncomplicated course of a disease--in 73.2%. Lethality after the emergency operations was 38.1% and considerably exceeded that after the elective interventions (7.8%). This dictates the necessity to improve the conservative hemostatic measures. PMID- 1875614 TI - [Biochemical criteria of early diagnosis of postoperative pancreatitis in oncologic patients]. AB - With the aim of diagnosis of postoperative pancreatitis in 88 oncologic patients operated on for malignant tumors of the upper alimentary canal and pancreatoduodenal zone, including those with trauma or resection of the pancreas, the comparative analysis of significance of different biochemical indices was carried out. A high sensitivity and informative value of measuring a content of the middle molecular mass peptides and components of kallikrein-kinin system with calculation of a toxicity coefficient permit to recommend their use as the additional diagnostic criteria. PMID- 1875615 TI - [Changes in cytotoxicity of natural killer cells and level of large granule containing lymphocytes in patients with lung cancer under the effects of cryosurgery]. AB - The parallel study of the content of large granule-containing lymphocytes (LGL) and natural killer activity (NKA) in donors, patients with benign tumors in the lungs and bronchial or pulmonary cancer in operative intervention and combined cryosurgical treatment was carried out. The stimulating effect of cryodestruction of malignant tumors with their subsequent spontaneous thawing on LGL content and NKA in patients was established. Administration of prodigiosan immunomodulator contributed to increase in natural resistance of an organism of the patients. The positive correlation of NKA and LGL content was noted. PMID- 1875616 TI - [Experience in the use of the AKA-2 device in the formation of esophago intestinal anastomosis]. AB - Two techniques of the compressive anastomosis formation were used. At the early postoperative period, there were no complications. Three months after the operation, 4 patients were examined. In 1, the cicatricial anastomotic stenosis, caused by the errors in technique of the anastomosis creation, was revealed. In the remaining 3 patients, there were no impairment in healing of an anastomosis. In 9 patients, in formation of an anastomosis, all the layers of the intestinal wall and only mucous membrane of the esophagus were stitched. No impairment in anastomotic healing was noted. Of the 16 patients operated on with the use of the AKA-2 apparatus (in all the cases, the compressing rings with a small diameter- 20 mm were used), 1 died at day 4 after the operation from ischemic insult of the brain. PMID- 1875617 TI - [Effectiveness of some methods in the treatment of primary squamous cell cancer of the skin]. AB - In studying the long-term results of treatment of 330 patients with primary planocellular cutaneous cancer treated by surgical or radial methods, it was established that surgical methods of treatment were more effective as compared with the radial ones in exophytic and endophytic tumor growth irrespective of its stage and location. No one of the methods employed permitted to achieve stable cure in ulcerous-infiltrative growth of a tumor. PMID- 1875618 TI - [Dysplasia of the epithelium of the gastric mucosa]. PMID- 1875619 TI - [Carcinoids]. AB - The clinical features, diagnosis, treatment and long-term results in 24 patients with carcinoids of the different organs were studied. Benign carcinoid was revealed in 2, that with a potential malignancy--in 2, a malignant one--in 20 patients. In 6 patients, the combination of carcinoid and cancer of different location was observed. A radical operation was performed in 17 patients. Nine patients died, of them 3--from spreading of cancer of different location. PMID- 1875620 TI - [Use of allograft of pancreatic islet cell cultures in complex treatment of acute purulent process in patients with diabetes mellitus]. AB - The results of treatment of 170 patients with diabetes mellitus and purulent wounds which appeared after opening the abscesses and phlegmons, and as well of 270 patients with gangrene of the lower extremities are presented. Early opening the abscess, improved quality of debridement of purulent wounds, and as well allotransplantation of pancreatic islet cell cultures (45 cases) permitted to stop progressing of the purulent process, place early secondary sutures, and in patients with the sutures placed, to achieve primary healing of the wounds. PMID- 1875622 TI - [Diagnosis and treatment of recurrences of duodenal ulcer perforation after its closure]. AB - In a work, the information about the patients who had their duodenal ulcer once (836 case), or twice (28) perforated is analysed. Recurrency of a perforative ulcer after its closure was noted in 1.4% of cases. After closure of a perforating ulcer, it is expedient to watch and examine the patients in a specialized institutions. In disease recurrency after closure of a perforative ulcer and ineffective therapy, the performance of radical operation preventing the subsequent development of a disease complication is indicated. PMID- 1875621 TI - [Effectiveness of a cryosurgical method in the treatment of primary localized skin cancer]. AB - The long-term results of cryosurgical treatment of primary localized cutaneous cancer were studied in 930 patients with 1154 solitary and primary multiple synchronous and metachronous tumors. A high effectiveness of the method was established. The maximum therapeutical effect was noted in patients with I stage tumors and exophytic form of growth, the minimal one--with IIA stage tumors and endophytic form of growth irrespective of their location and histologic structure. PMID- 1875623 TI - [High resection of the left testicular vein and ligation of the internal iliac artery using a retroperitoneoscope]. AB - In 90 youths at the age of from 14 to 16 years suffering from left-sided varicocele, the authors have used a retroperitoneoscope for high ligation and transection of the testicular vein. There were no complications at the time of operation and after it. In control examination 1.5-2 years later, no varicocele recurrences were revealed. In 15 patients with profuse bleeding from carcinomatous tumor of the urinary bladder, the authors performed ligation of the internal iliac arteries by means of a retroperitoneoscope. PMID- 1875624 TI - [Metastatic involvement of regional lymph nodes and long-term results of the treatment of patients with cancer of the thoracic part of the esophagus]. AB - The patients who underwent the radical operations for cancer of the thoracic esophagus were subdivided into three groups: group 1--patients with no metastatic involvement of the regional lymph nodes (N0); group 2--with enlarged regional lymph nodes because of their hyperplasia, but without metastatic involvement (NX); group 3--with metastatic involvement of the regional lymph nodes (N1). The best results of 5-year survival after radical operation (50.2%) were noted in patients with a tumor size less than 3 cm, infiltration of only muscular layer, high degree of cancer differentiation, without metastatic involvement of regional lymph nodes. In presence of metastases, the 5-year survival was 6.01%. Discovering at operation the enlarged lymph nodes is a poor prognostic sign, 5 year survival of these patients do not exceed 9%. PMID- 1875625 TI - [Current problems in the diagnosis and treatment of thyroid cancer]. PMID- 1875626 TI - [Characteristics of healing of anastomoses in surgery of the alimentary tract performed with laser irradiation]. PMID- 1875627 TI - [Retroperitoneal ganglioneuroma simulating appendiceal infiltrate]. PMID- 1875628 TI - [Combined gastrectomy after exploratory laparotomy in gastric lymphosarcoma]. PMID- 1875629 TI - [Successful treatment of a patient with perforation of bleeding gastric tumor]. PMID- 1875630 TI - [Metastasis of melanoma into the stomach and small intestine]. PMID- 1875631 TI - [Leiomyosarcoma in a patient with multiple malignant neoplasms]. PMID- 1875632 TI - [Development of 2 cancerous tumors from malignant gastric ulcer after perforation]. PMID- 1875633 TI - [10-year result of repeated laparotomy with subtotal gastric resection for cancer in a patient with tuberculous cervical lymphadenitis]. PMID- 1875634 TI - [Dysplasia of the epithelium of the gastric mucosa and cancer]. PMID- 1875635 TI - [A case of hepatic lipoma]. PMID- 1875636 TI - [Ecchondroma of the ribs]. PMID- 1875637 TI - [Uncommon localization of accessory mammary glands]. PMID- 1875638 TI - [Benign tumors of the stomach and intestine]. PMID- 1875639 TI - [Giant leiomyoma of the stomach]. PMID- 1875640 TI - [A rare source of acute gastric hemorrhage]. PMID- 1875641 TI - [Pleomorphic adenoma of soft tissues of the thigh]. PMID- 1875642 TI - [Lymphangioma of the abdominal cavity]. PMID- 1875643 TI - [A case for storage and transportation of biopsy materials]. PMID- 1875644 TI - [Causes of late diagnosis of cancer of the large intestine and its complications]. AB - The results of treatment of 44 patients with complicated colonic cancer were studied. It was established that at the prehospital stage, more 60% of them were not examined purposefully, although there were indications for such an examination. Early symptoms of development of a colonic tumor were revealed. The main causes of late diagnosis were the inadequate oncologic watchfulness of the polyclinical physicians, and as well a low level of organization of the prophylactic medical examinations. PMID- 1875645 TI - [Clinical aspects and diagnosis of early signs of cerebrovascular insufficiency]. PMID- 1875646 TI - [Etiology, pathogenesis, clinical aspects and prevention of acquired immunodeficiency syndrome]. AB - It is suggested that etiology, pathogenesis and clinical pattern of HIV-infection advanced stages (AIDS) may be closely associated with acute accidental involution of the thymus and activity of the hypothalamic-pituitary-adrenal axis in 10-35 year-olds. Feasibility of preventing the disease progression in HIV-infected individuals by stimulation of microcirculation in the thymic cortex needs further investigations. PMID- 1875647 TI - [Once more about interstitial nephritis]. AB - A comparative study was made of 25 patients (Group 2, control) with documented pyelonephritis and 55 patients (Group 1) who had a morphological picture of chronic interstitial inflammation without signs of abnormal urodynamics, bacteriuria, urographic and sonographic evidence of pyelonephritis. All the patients underwent life-time morphological study, their immunological spectrum (IgA, IgG, IgM, IgE) was explored. They had a test for sensitization of a peripheral blood mononuclear fraction to one or several drugs which had been given to the patients. The patients from Group 1 displayed significantly elevated IgE levels and a regularly detected sensitization of mononuclears to one or several drugs. Morphologically, there were signs of congenital renal tissue dysplasia in the presence of diffuse interstitial inflammation. Positive immunofluorescence findings were seen in the tubular wall of 10 (18%) patients. The findings made it possible to define diagnostic criteria for interstitial nephritis, a nosological entity. PMID- 1875648 TI - [Training of general practitioners]. PMID- 1875649 TI - [Value of experience in medical practice]. PMID- 1875650 TI - [Stable stenocardia as a form of ischemic heart disease]. PMID- 1875651 TI - [A.P. Chekhov and military medicine]. PMID- 1875652 TI - [Clinical pharmacology of diuretics]. PMID- 1875653 TI - [Clinical value of determining the fibronectin level in internal diseases]. PMID- 1875654 TI - [Evaluation of compensatory possibilities of the cardiovascular system in patients before reconstructive operations on the aorta and major arteries]. AB - To determine functional reserves of cardiovascular system, two procedures were comparatively studied in evaluation of central hemodynamics: tetrapolar chest rheography under isovolemic loading and rheopolyglucin test. Close correlation registered in results of the tests allowed the authors to employ subsequently the isovolemic test alone. The patients with circulatory subcompensation and decompensation received 7-14-day preoperative cardiostimulation. PMID- 1875655 TI - [Experience with using balloon dilatation of the coronary arteries]. AB - The paper presents the analysis of balloon dilations of the coronary arteries in 18 patients with ischemic heart disease. A multimodality clinical examination of the patients involving provocative tests and echocardiography is recommended to be performed both preoperatively and postoperatively. PMID- 1875656 TI - [Restoration of coronary circulation and left-ventricular function after thrombolytic therapy of acute myocardial infarction in elderly patients]. PMID- 1875657 TI - [Causes of diagnostic errors in ventricular pre-excitation syndrome associated with mitral valve prolapse]. AB - Clinical appearance and misdiagnosis in 27 patients having associated preexcitation syndrome and mitral prolapse have been analyzed. Misdiagnosis of myocardial infarction, rheumatic and congenital heart disease, infectious allergic myocarditis were most typical errors in this condition identification: in 9, 3 and 2 patients, respectively. PMID- 1875658 TI - [Diastolic mitral regurgitation in atrioventricular block]. AB - Diastolic mitral block was revealed by ++Doppler echocardiography in patients with atrioventricular block degree I, II and III in atrial flutter. The leading mechanism in pathogenesis of diastolic mitral regurgitation lies in delayed contraction of the left ventricle in relation to the left atrium causing incomplete closure of mitral cusps. Other factors contributing to diastolic mitral insufficiency involve overloading of the left ventricle and rigidity of its myocardium. All the patients with atrioventricular block and diastolic mitral regurgitation showed tricuspid diastolic regurgitation. Diastolic mitral regurgitation induces volumetric overloading of the left atrium. PMID- 1875659 TI - [Characteristics of the changes in echocardiographic indicators of the electric cardiac pacing in alcoholics]. AB - To specify cardiovascular function in alcoholics (74 males capable for work by their age) of stage II, they under went M-mode ECG at the height of the rhythm induced by transesophageal pacing. One third of the examinees demonstrated worsening of the left ventricular contractility evident from reduced ejection fraction (by 17.1%) and shorter anteroposterior size of the left ventricle (diminution by 18.1%). Paradoxical movement of the interventricular septum in the systole emerged in one fifth of the patients at the height of the stimulation. It is believed important to identify a group of patients with initially abnormal intracardiac hemodynamics (13.6%). They suffered further deterioration of myocardial contractility. The study of ECG findings at the height of atrial stimulation detects latent alcoholic myocardiodystrophy. PMID- 1875660 TI - [The role of gastroduodenal diseases in the development of cardiac arrhythmia of the sick sinus syndrome type]. AB - A total of 105 patients with suspected sick sinus syndrome were examined. All of them underwent transesophageal pacing and endoscopical investigation. A relationship is shown between lesions of the gastrointestinal tract and emergence of the sinus vagal depression leading to various disturbances of cardiac rhythm. PMID- 1875661 TI - [Radiological diagnosis--current problems and achievements]. PMID- 1875662 TI - [Causes of errors in the current diagnosis of infectious endocarditis]. PMID- 1875663 TI - [Non-invasive diagnosis of lesions of peripheral blood vessels in patients with diabetes mellitus]. AB - Clinical examination of 51 diabetes mellitus patients with the disease running a severe, moderate and light course included ultrasound dopplerography to measure arterial and venous pressure on the malleolus and photoplethysmography to evaluate arterial pressure in the great toe. There appeared a relationship between the disease severity and venous pressure, toe pressure index, pressure gradient malleolus--toe. The closest correlation was with the venous pressure. At late stages of diabetic angiopathy calcinosis of the arterial wall distorts real value of malleolar systolic pressure necessitating multimodality investigation of peripheral vessels in diabetic patients. PMID- 1875664 TI - [New aspects of using adrenomimetics in the diagnosis and treatment of bronchial asthma]. AB - It is suggested to use alpha-stimulating effect of naphthyzine and halazoline for pharmacological spirometric testing in evaluating the inflammatory-edematous component of bronchial obstruction. These anti-edema agents combined with standard bronchospasmolytics (beta 2-agonists and cholinolytics) proved effective in arresting episodes of asphyxia. Optimal doses of naphthyzine and halazoline, related side effects have been clarified in case of their addition to selective beta 2-agonists, cholinolytics and combinations thereof. In contrast to nonselective adrenomimetic drugs adrenaline and ephedrine, naphthyzine, halazoline or similar medicines do not produce cardiostimulation this justifying their use in combination with selective bronchospasmolytic berotec, salbutamol , berodual and atrovent. PMID- 1875665 TI - [Principles of conservative treatment of trophic leg ulcers]. AB - Long-term experience gained in the treatment of 647 patients suffering from trophic ulcer of the leg due to chronic venous insufficiency led the author to the conclusion on minimal benefit of chemotherapy in the treatment of the condition. Good therapeutic effect was achieved with enzymes used for cleansing purposes and local elastic compression of the leg with 3% boric acid solution fomentation. Epithelialization ++ of the ulcer occurred in 86.2% of the patients. PMID- 1875666 TI - [Drug therapy of pulmonary and portal hypertension in liver cirrhosis]. AB - Detailed examination of hemodynamics in patients with portal and pulmonary hypertension was performed upon acute drug tests and course administration of nitrosorbide++, corinfar and propranolol. Ultrasound and rheography investigations were employed to elucidate the relations between portal and pulmonary hypertension in cirrhosis patients. Criteria of early diagnosis are discussed. Nitrosorbide++ produced positive effect on hepatic blood flow, corinfar improved pulmonary hemodynamics in lack of its influence on hepatic blood flow, while propranolol resulted in the drop of both portal and pulmonary hypertension, normalization of general hemodynamics. PMID- 1875667 TI - [Hemodynamics of the lesser circulation and pulmonary ventilation in patients with chronic glomerulonephritis and chronic renal failure]. AB - Examination of 97 chronic glomerulonephritis sufferers with various degrees of chronic renal failure revealed a rise of the average dynamic pressure in the pulmonary artery and alterations in pulmonary ventilation. The most pronounced shifts were registered in associated chronic renal failure of degree II. PMID- 1875668 TI - [The renin-angiotensin-aldosterone system and arterial hypertension in patients with rheumatoid arthritis]. AB - Renin-angiotensin-aldosterone++ system was investigated in 60 patients suffering from rheumatoid arthritis. Forty-four of them (group 1) had arterial hypertension (144 +/- 4/94 +/- 2 mm Hg), sixteen were free of hypertension (120 +/- 3/80 +/- 1 mm Hg). Twenty-nine control subjects comparable by AH standing and demographic parameters had essential hypertension stage IB-IIA by A. L. Myasnikov classification (141 +/- 3/89 +/- 1 mm Hg). A tendency to renin suppression was dominating in 72% of group 1 patients (plasma renin activity less than 1.0 ng/ml/h). In this group there appeared high concentrations of A II (14.2 +/- 3.1 pg/ml) and plasma aldosterone++ (238 +/- 94 ng/ml). Rheumatoid vasculitis manifested in 86% of patients. Control subjects exhibited plasma renin activity greater than 3.0 ng/ml/hin 48%, average A II concentration was similar to that of group 1 (12.4 +/- 2.7 ng/ml/h, p greater than 0.05), plasma aldosterone++ level was significantly lower (176 +/- 29 ng/ml, p less than 0.05). Correlations were established between A II concentration and ESR (r = 0.39, p less than 0.05), A II and rheumatoid factor titers (r = 0.40, p less than 0.05). These indicate that immunopathological reactions are responsible for shifts in renin-angiotensin aldosteron system in hypertensive rheumatoid arthritis subjects. PMID- 1875669 TI - [Evaluation of biochemical studies in the diagnosis of the cholestasis syndrome]. PMID- 1875670 TI - [Use of infrared spectrophotometry of bile for diagnosis of cholelithiasis and predicting the chemical composition of the concrements]. AB - Infrared spectrophotometry was applied in bile investigation from 47 cholelithiasis, 53 acalculous chronic cholecystitis and 23 control subjects. A cholelithiasis--specific shift in the absorption band appeared in the range of 900-1150 cm-1. Bile calculi removed at surgery from 110 relevant patients and bile from them were exposed to infrared spectrophotometry. The authors derived a correlation between the shape of the absorption band for bile in the range of 1500-1800 cm-1 and chemical composition of the concrement. PMID- 1875671 TI - [Study of central and porto-hepatic hemodynamics before the surgical treatment of patients with liver cirrhosis and portal hypertension]. AB - Basing on the results of hemodynamic findings related to the heart and liver in 41 patients with hepatic cirrhosis and portal hypertension (33 of them were operated on for portal hypertension), it is suggested that when deciding on the type of surgery in such patients, initial status of central and portal hemodynamics as well as expected changes in these parameters due to surgery should be taken into consideration. Pathogenetic grounds for some routine interventions in hepatic cirrhosis and portal hypertension are thought open to question. PMID- 1875672 TI - [Clinical characteristics of acute cholecystitis in males]. AB - The analysis of 682 case histories of males suffering from acute cholecystitis suggested a conclusion on occasional deviations in clinical manifestations of the disease in males. Various combinations of complications are not a rare finding making the diagnosis problematic. Acute destructive process in the gall bladder occurs in the presence of chronic inflammatory and infiltrative alterations in the hepatopancreatoduodenal area. Clinically, general symptoms of endotoxicosis dominate, local signs presenting indistinctly. Late diagnosis results in late surgical treatment: 9.2% of the admitted patients only are operated on within 24 hours since hospitalization. The authors hold that choledochotomy is indicated to 50.7% of the patients. Lethal postoperative outcome was registered in 2.2% of those operated on. The deaths were attributed to cardiovascular and hepatic failure. PMID- 1875673 TI - [Enterosorption in the combined treatment of patients with multiple sclerosis]. AB - Fifty-nine patients exhibiting an exacerbation of multiple sclerosis were examined for efficacy of enterosorption with the fibrous coal sorbent vaulen. The solvent powder was administered 3 times a day in a dose of 50-60 mg/kg for 20 days between meals. The relief of neurological symptoms started on treatment days 3-4 with subsequent attenuation within the course of treatment. This agreed with discontinuation of liquor hypertension and recovery of normal immunological spectra of serum parameters. The method of enterosorption is simple, safe and readily arrests the disease exacerbation. PMID- 1875674 TI - [Cardiac lesion in a young woman caused by amitriptyline poisoning with subsequent long-term intake of pyrazidol]. PMID- 1875675 TI - [Leopard syndrome with clear phenotypic manifestations]. PMID- 1875676 TI - [Chronic bronchitis: developmental mechanisms and the principles of the treatment and prevention]. PMID- 1875677 TI - [Drug therapy of chronic pancreatitis]. AB - Potentialities of current chemotherapy of chronic pancreatitis are delineated. An individual approach is advocated for patients with the primary and secondary disease varying in etiology, for those with and without external and internal pancreatic insufficiency. Indications are validated for application of drugs distinct from each other by mechanism of action and intended for pain relief, of kallikrein-protease and other trypsin inhibitors, replacement polyenzymatic therapy, stimulators of pancreatic exocrine secretion, antihistamine drugs, parenteral feeding, vitamins, detoxicating, immunomodulating and psychopharmacological agents. Approaches to management of chronic pancreatitis and its complications as well as associated diseases are detailed. Chronic pancreatitis sufferers must be followed up and undergo prophylactic treatment. PMID- 1875678 TI - Depression and self-enhancement among Japanese and American students. AB - This study examined the cultural generalizibility of the negative relationship between depression and self-enhancement. Japanese (n = 116) and American (n = 125) students completed the Zung (1965) Self-Rating Depression Scale and three measures of self-enhancement (i.e., the tendency to see oneself in a positive light). As expected, Japanese subjects were found to be more depressed and less self-serving than Americans. Negative correlations between depression and self enhancement measures were obtained for both samples. Regression analyses of the relationships between measures indicated that sample differences in self enhancement were explained largely by sample differences in depression. It is proposed that, relative to the Americans, Japanese students had a negative self schema that led to higher depression and lower self-enhancement. PMID- 1875679 TI - Factors affecting philanthropic behavior of Jewish adolescents. AB - A field study of children's philanthropic behavior, focusing specifically on the giving patterns of adolescents, was conducted in a Jewish school in the United States over a 5-month period. Classrooms were observed by using ethnographic methods, and a written questionnaire was administered to seventh- through ninth graders (N = 48). Monetary records from 23 class sessions were analyzed. Giving to charity was inversely related to age, with the oldest students in the school giving the least. Both teachers of adolescents and the majority of the adolescents attributed this finding to the dispositions of the givers rather than to contextual factors in the school or to the nature of the charitable enterprise. PMID- 1875680 TI - Factors affecting relationships of Turkish adolescents with parents and same-sex friends. AB - The present study attempted to investigate the differences between Turkish late adolescents' relationships with their parents and friends by using Armsden and Greenberg's (1987) scales for measuring attachment. In addition, an attempt at determining predictors of different aspects of attachment was made. The findings were that (a) similar dimensions of attachment emerged from a factor analysis of Turkish data when compared with Armsden and Greenberg's factors, (b) the data provide evidence for the argument that relationships should be studied with an awareness that they exist within a sociological background that includes other relationships, and (c) regression analysis predicting different aspects of attachment indicated that different variables may be important as determinants of men's and women's relationships with significant others. PMID- 1875683 TI - Tissue engineering. Selected papers from the UCLA Symposium of Tissue Engineering. Keystone, Colorado, April 6-12, 1990. PMID- 1875681 TI - Date rape: expectations, avoidance strategies, and attitudes toward victims. PMID- 1875682 TI - Locus of control, depression, and suicidal ideation among American, Philippine, and Turkish students. PMID- 1875684 TI - Recipes for reconstituting skin. AB - Reconstituted Living Skin Equivalent (LSE) is made up of a dermal equivalent (DE) on which keratinocytes are plated where they give rise to a multilayered differentiated epidermis. The dermal equivalent develops through interactions between fibroblasts and collagen fibrils that begin to form after the cell-matrix precursor is cast. The gel that forms as a result of collagen polymerization and fluid trapping is contracted uniformly in all dimensions. By securing it at ends and edges in the mold in which it is cast, the final dimensions, strength and morphology of the forming tissue are altered. The same phenomena are seen in casting tubular tissues for the fabrication of small caliber blood vessel equivalents. The cells of the dermal equivalent are biosynthetically active and enrich the matrix to different degrees with secretory products, depending on how the cells are stimulated and on the presence or absence of an epidermis. Collagen biosynthesis by dermal cells in the DE is sensitive to growth factors, ascorbate concentrations and amino acid pools. Both ascorbate and TGF beta 1 increase total collagen biosynthesis at least two-fold by one week after tissue formation. With TGF beta 1 present, the capacity of cells in the DE to synthesize collagen increases with time, over a two-week period. If ascorbate (200 micrograms/ml) is added just after the tissue is cast and daily thereafter, contraction lattice is blocked, and collagen biosynthesis is enhanced relative to contracted controls that had received 200 micrograms/ml ascorbate once. The increase was nearly an order of magnitude over that of controls and was coordinate with a comparable increase in hyaluronate and sulfated glycosaminoglycan (GAG) production as shown by TCA-precipitable glucosamine in the intercellular matrix of the DE. Both the LSE and the Living Dermal Equivalent (LDE) exhibit complex responses to UV radiation and to various chemicals that are greatly different from responses given by monolayered cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875685 TI - Optimization of human endothelial cell attachment to vascular graft polymers. AB - Endothelial cells (EC) covering the blood-contacting surface of a prosthetic material could potentially enhance the subsequent nonthrombogenicity of the surface. In order to create such a surface, the EC must become attached to the surface, spread and ultimately form a monolayer. In this study we examined several factors that influence these processes. On ePTFE surfaces, surface pretreatment with human serum for 30 minutes at a concentration of 1.4 gm percent protein resulted in significantly more attached EC when compared to other concentrations or when compared to fetal calf serum or human serum albumin. The rate of EC spreading was strongly influenced by temperature, with a maximum occurring at 37 degrees C. During real-time video microscopy, it was noted that the rate of EC attachment and spreading was primarily dependent on arrival of the EC to the surface rather than attachment and spreading. Thus as a method of increasing EC delivery, the concept of filtering EC onto the graft lumenal surface was tested by pressurizing the graft lumen to speed EC delivery to the surface. This technique produced a 2 to 5-fold increase in EC attachment when compared to gravity forced cell deposition. We conclude that an ePTFE graft can be rapidly endothelialized using these simple measures. PMID- 1875686 TI - Effects of pulsatile flow on cultured vascular endothelial cell morphology. AB - Endothelial cells (EC) appear to adapt their morphology and function to the in vivo hemodynamic environment in which they reside. In vitro experiments indicate that similar alterations occur for cultured EC exposed to a laminar steady-state flow-induced shear stress. However, in vivo EC are exposed to a pulsatile flow environment; thus, in this investigation, the influence of pulsatile flow on cell shape and orientation and on actin microfilament localization in confluent bovine aortic endothelial cell (BAEC) monolayers was studied using a 1-Hz nonreversing sinusoidal shear stress of 40 +/- 20 dynes/cm2 (type I), 1-Hz reversing sinusoidal shear stresses of 20 +/- 40 and 10 +/- 15 dynes/cm2 (type II), and 1 Hz oscillatory shear stresses of 0 +/- 20 and 0 +/- 40 dynes/cm2 (type III). The results show that in a type I nonreversing flow, cell shape changed less rapidly, but cells took on a more elongated shape than their steady flow controls long term. For low-amplitude type II reversing flow, BAECs changed less rapidly in shape and were always less elongated than their steady controls; however, for high amplitude reversal, BAECs did not stay attached for more than 24 hours. For type III oscillatory flows, BAEC cell shape remained polygonal as in static culture and did not exhibit actin stress fibers, such as occurred in all other flows. These results demonstrate that EC can discriminate between different types of pulsatile flow environments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875687 TI - Endothelialization of the luminal sac in artificial cardiac prostheses: a challenge for both biologists and engineers. AB - Thromboembolic complications are a major obstacle for the permanent use of artificial cardiac prostheses. Many of these complications are caused by the intrinsic thrombogenicity of the biomaterials, which are used to cast the luminal blood sac. Numerous attempts have been made to improve the hemocompatibility of the new generation of totally implantable blood pumps, mainly by physico-chemical modifications of the biopolymeric materials and the blood contacting surfaces. We, on the other hand, believe that the most promising and challenging approach, from both the biologists' and engineers' point of view, is to coat the luminal surfaces of cardiac prostheses with a functional monolayer of autologous endothelial cells (ECs) and thus reproduce "nature's biocompatible blood container." The key to lining an artificial heart with a nonthrombogenic monolayer of endothelial cells is to explore the molecular and cellular mechanisms which render the EC lining inside the beating ventricle nonthrombogenic and resistant to flow-induced shear stresses and cyclic, tensional deformations. This knowledge has then to be translated into biotechnological know-how, in order to maintain an intact EC monolayer inside the blood sac of an artificial device. In this paper we emphasize some of the bioengineering issues associated with the endothelialization of the luminal sac, and also discuss some aspects related to the blood sac itself. PMID- 1875688 TI - Bioengineering in development of the hybrid artificial pancreas. AB - The hybrid artificial pancreas for treatment of diabetes consists of insulin secreting pancreatic tissue which is surrounded by a membrane that protects the tissue from rejection by the immune system following implantation. In this paper, we review the alternative therapeutic approaches for diabetes under study and then discuss the technical requirements that must be met by a hybrid device useful to humans. Previous work on intravascular and extravascular immunoisolation devices is reviewed from the standpoint of these requirements, and three critical unresolved issues are discussed: biocompatibility, oxygen supply limitations, and prevention of immune rejection. PMID- 1875689 TI - Hematopoiesis on suspended nylon screen-stromal cell microenvironments. AB - A three-dimensional culture system for the growth of primate and rodent bone marrow was developed in our laboratory. This method involves the seeding of stromal cells onto a nylon screen and the inoculation of fresh or cryopreserved bone marrow hematopoietic cells after stromal cell processes had extended across 3 to 4 out of every 5 mesh openings. Stromal cells attach, grow, and secrete matrix proteins which contribute to an intricate microenvironment for the support of multilineage hematopoiesis, which was observed for greater than 270 days in the rat model and for greater than 12 weeks in the human system, as evidenced by flow cytometry analysis and in vitro clonogenic assays. The adherent zones of these suspended nylon screen cultures consisted primarily of immature cells. These cultures could also be used as substrates for cytotoxicity measurements; treatment of rat bone marrow cultures of various ages with cytosine beta-D arabinofuranoside, cyclophosphamide, 5-fluorouracil, or methotrexate resulted in a dose-dependent decrease in CFU-C numbers and altered the phenotypic distribution of hematologic cells in the adherent zone. The use of a modification of this method to generate large numbers of active cytolytic cells after greater than 75 days culture of rat bone marrow-derived natural killer cells is described also. Suspended nylon screen bone marrow culture also has potential uses in genetic insertion and graft vs. host disease studies, blood component therapy, the evaluation of ex vivo purging programs, and in marrow expansion for transplantation. PMID- 1875690 TI - Transplantation of polymer encapsulated neurotransmitter secreting cells: effect of the encapsulation technique. AB - Deficits associated with neurological diseases may be improved by the transplantation within the brain lesioned target structure of polymer encapsulated cells releasing the missing neurotransmitter. Surrounding cells with a permselective membrane of appropriate molecular weight cut-off allows inward diffusion of nutrients and outward diffusion of neurotransmitters, but prevents immunoglobulins or immune cells from reaching the transplant. This technique therefore allows transplantation of post-mitotic cells across species. It also permits neural grafting of transformed cell lines since the polymer capsule prevents the formation of tumors by physically sequestering the transplanted tissue. In the present study, we compared the ability of dopamine-secreting cells, encapsulated by 2 different methods, to reverse experimental Parkinson's disease, a neurodegenerative disease characterized by motor disturbances due to a lack of dopamine within the striatum following degeneration of the dopaminergic nigro-striatal pathway. PC12 cells were loaded in polyelectrolyte-based microcapsules or thermoplastic-based macrocapsules and maintained in vitro or transplanted in a rat experimental Parkinson model for 4 weeks. Chemically induced depolarization increased the in vitro release of dopamine from macrocapsules over time, while no increase in release was observed from microcapsules. Encapsulated PC12 cells were able to reduce lesion-induced rotational asymmetry in rats for at least 4 weeks, regardless of the encapsulation technique used. With both encapsulation methods, PC12 cell viability was greater in vivo than in vitro which suggests that the striatum releases trophic factors for PC12 cells. More brain tissue damage was observed with microcapsules than macrocapsules, possibly the result of the difficulty of manipulating the more fragile microcapsules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875691 TI - Semipermeable polymer tubes provide a microenvironment for in vivo analysis of dorsal root regeneration. AB - The regeneration of lesioned axons is critically influenced by the local microenvironment. In this study, semipermeable polymer tubes were used to provide a defined microenvironment in vivo to analyze the regeneration of dorsal root axons under various conditions in the adult rat. Cut dorsal root fibers grew across a 2.7 mm gap within enclosed polymer tubes by 4 weeks. The pattern of axonal outgrowth was dramatically influenced by mechanical factors such as the inner surface topography of the polymer tube. Tubes containing various molecular and cellular substrates were also used to study their effect on dorsal root regeneration. PMID- 1875692 TI - Recent progress in bone induction by osteogenin and bone morphogenetic proteins: challenges for biomechanical and tissue engineering. AB - Implantation of demineralized bone matrix results in local bone induction. Bone induction is a sequential biological chain reaction that consists of chemotaxis and proliferation of mesenchymal cells and differentiation of bone. Osteogenin, a bone morphogenetic protein has been purified and the amino acid sequence determined. Recently a family of bone morphogenetic proteins have been cloned and expressed by recombinant DNA technology. The availability of growth and morphogenetic factors will permit the rational design of new bone. The challenge for the biomechanical engineer is to attain mechanically optimal and functionally adaptive new bone for various skeletal prostheses. We are on the threshold for fabrication of new bone based on sound architectural design principles of tissue engineering based on cellular and molecular biology of growth and differentiation factors. PMID- 1875693 TI - Candidates for the mechanosensory system in bone. AB - Some potential mechanisms by which bone cells sense mechanical loads are described and hypotheses concerning the functioning of these mechanisms are explored. It is well known that bone tissue adapts its structure to its mechanical load environment. Recent research has illuminated the biological response of bone to mechanical loading at the cellular level, but the precise mechanosensory system that signals bone cells to deposit or resorb tissue has not been identified. The purpose of this paper is to describe the current status of this research and to suggest some possible mechanosensory systems by which bone cells might sense environmental loads. PMID- 1875694 TI - Experimental studies on repair of large osteochondral defects at a high weight bearing area of the knee joint: a tissue engineering study. AB - There is a vast clinical need for the development of an animal model to study the fundamentals of healing of injured or diseased diarthrodial joints (knee, hip, shoulder, wrist, etc). Current prosthetic replacements do not offer acceptable treatment for injuries and diseases of these joints in young active individuals. New clinical treatment modalities, based on sound biologic principles, are sought for the development of repair or healing tissues engineered to have similar biomechanical properties as normal articular cartilage. In this paper we present a brief review of this need, and propose a grafting procedure which may lead to a successful animal model for studies of long term repair of major osteochondral defects. This grafting procedure uses an autologous periosteum-bone graft or an autologous-synthetic bone replacement graft. We have applied these grafts for in vivo repair of large surgically created defects in the high weight bearing area of the distal femoral condyle of mature New Zealand white rabbits. Further, an interdisciplinary study, including histochemistry, biochemistry (composition and metabolic activities), and biomechanics (biphasic properties), was performed to assess the feasibility of our animal model to generate viable repair tissues. We found our grafting procedure produced, 8 weeks postoperatively, tissues which were very similar to those found in normal articular cartilage. However, our histological studies indicate incomplete bonding between the repair tissue and the adjacent cartilage, and lack of an appropriate superficial zone at the articular surface. These deficiencies may cause long term failure of the repair tissue. Further studies must be undertaken to enhance development of a strong bond and a collagen-rich surface zone. This may require the use of growth factors (e.g., transforming growth factors beta) capable of simulating extra collagen production, or the use of serum derived tissue glue for bonding. At present, we are pursuing these studies. PMID- 1875695 TI - The effects of knee motion and external loading on the length of the anterior cruciate ligament (ACL): a kinematic study. AB - A six-degrees-of-freedom mechanical linkage device was designed and used to study the unconstrained motion of ten intact human cadaver knees. The knees were subjected to externally applied varus and valgus (V-V) moments up to 14 N-m as well as anterior and posterior (A-P) loads up to 100 N. Tests were done at four knee flexion angles; 0, 30, 45, and 90 deg. Significant coupled axial tibial rotation was found, up to 21.0 deg for V-V loading (at 90 deg of flexion) and 14.2 deg for A-P loading (at 45 deg of flexion). Subsequently, the knees were dissected and the locations of the insertion sites to the femur and tibia for the anteromedial (AM), posterolateral (PL), and intermediate (IM) portions of the ACL were identified. The distances between the insertion sites for all external loading conditions were calculated. In the case when the external load was zero, the AM portion of the ACL lengthened with knee flexion, while the PL portion shortened and the intermediate (IM) portion did not change in length. With the application of 14 N-m valgus moment, the PL and IM portions of the ACL lengthened significantly more than the AM portion (p less than 0.001). With the application of 100 N anterior load, the AM portion lengthened slightly less than the PL portion, which lengthened slightly less than the IM portion (p less than 0.005). In general, the amount of lengthening of the three portions of the ACL during valgus and anterior loading was observed to increase with knee flexion angle (p less than 0.001). PMID- 1875696 TI - A finite helical axis as a landmark for kinematic reference of the knee. AB - Reference coordinates based on the finite helical axis for flexion of the knee from 0 to 90 deg are proposed. Six degree-of-freedom tracking allows the use of such a helical axis as a kinematic landmark for knee motion representation. Data from five human subjects in vivo are presented as a path of finite helical axes for flexion of the knee from 20 to 80 deg. The finite helical axis rotates by an average of 11.4 deg, the centrode translates an average of 19.8 mm, and the total axial translation averages 0.1 mm during flexion from 20 to 80 deg. Error due to the transducer was measured on a fixed-pivot pendulum and found to be 1.0 deg and 1.9 mm rms for the helical axis orientation and position, respectively, and 0.1 mm for the axial translation. Reproducibility and soft tissue effects on the measurements were repeatable to 4.0 deg and 2.7 mm rms in orientation and position, respectively, and 0.1 mm for the axial translations. Soft tissue errors averaged 4.9 deg and 3.6 mm in position and orientation, and 0.3 mm in the axial translations. PMID- 1875697 TI - Gas transport in serpentine microporous tubes under steady and pulsatile blood flow conditions. AB - A serpentine gas exchange unit was built with cylindrical tubular microporous membranes featuring periodic arcs with a fixed curvature ratio (ratio of tube radius to radius of curvature) of 1/14 and circular angles between 30 and 360 deg. Oxygen transfer was measured under steady and pulsatile blood flow conditions in vitro and ex vivo to assess the design features which most effectively augment gas transfer. Under steady blood flow conditions, oxygen transfer increased with circular angles beyond 70 deg. Under pulsatile conditions, a wide range of geometrical and fluid mechanical parameters could be combined to enhance gas transfer performance, which eventually depended upon the secondary Reynolds number and the Womersley parameter. PMID- 1875698 TI - Estimating three-dimensional temperature fields during hyperthermia: studies of the optimal regularization parameter and time sampling period. AB - During hyperthermia therapy it is desirable to know the entire temperature field in the treatment region. However, accurately inferring this field from the limited number of temperature measurements available is very difficult, and thus state and parameter estimation methods have been used to attempt to solve this inherently ill-posed problem. To compensate for this ill-posedness and to improve the accuracy of this method, Tikhonov regularization of order zero has been used to significantly improve the results of the estimation procedure. It is also shown that the accuracies of the temperature estimates depend upon the value of the regularization parameter, which has an optimal value that is dependent on the perfusion pattern and magnitude. In addition, the transient power-off time sampling period (i.e., the length of time over which transient data is collected and used) influences the accuracy of the estimates, and an optimal sampling period is shown to exist. The effects of additive measurement noise are also investigated, as are the effects of the initial guess of the perfusion values, and the effects of both symmetric and asymmetric blood perfusion patterns. Random perfusion patterns with noisy data are the most difficult cases to evaluate. The cases studied are not a comprehensive set, but continue to show the feasibility of using state and parameter estimation methods to reconstruct the entire temperature field. PMID- 1875699 TI - Analytical model of corneal surgery. AB - We present a model of the human cornea in order to study the changes in its shape resulting from surgical operations (e.g., radial keratotomy). A simple closed form solution is given for a thin linearly elastic spherical shell model of the cornea. We assume axisymmetry and isotropy in the shell surface. The surgery is modeled by permitting Young's modulus and shell thickness to depend on position. The analytical nature of the solution permits principal shell curvatures to be explicitly calculated. The model is used to investigate the effect of surgery on corneal flattening and the associated sensitivity to intraocular pressure changes. PMID- 1875700 TI - Changes in the incidence of alcohol-impaired driving in the United States, 1973 1986. AB - Studies of motor vehicle fatality data have indicated that alcohol involvement in fatal crashes has declined substantially in the United States since 1980. To determine the actual incidence of alcohol-impaired drivers on U.S. roads, a national roadside survey using portable breath-testing devices was carried out in 32 localities in the spring of 1986. The same sampling design and survey procedures used in a 1973 national roadside survey were followed as much as possible. The 1986 survey found 3.1% of the late-night weekend drivers to have a blood alcohol concentration (BAC) of 0.10% or more, compared to 4.9% of drivers in 1973. Similarly, 8.3% of the 1986 drivers were at or above 0.05% BAC, compared to 13.5% in 1973. The data indicate that the incidence of alcohol-impaired driving on weekend nights has fallen by one-third or more in the United States since 1973 and that the decline affected most population subgroups. PMID- 1875701 TI - Alcohol-related relative risk of fatal driver injuries in relation to driver age and sex. AB - The relative risks of fatal crash involvement at various blood alcohol concentrations (BACs) were examined using data on fatal driver injuries from the Fatal Accident Reporting System in conjunction with driver exposure data from the second national road-side breath-testing survey. Based on driver fatalities in single-vehicle crashes, it was estimated that each 0.02 percentage increase in the BAC of a driver with non-zero BAC nearly doubles the risk of being in a fatal crash. Crash risk was found to increase with increasing BAC among all of the six age and sex groups studied. At BACs in the 0.05-0.09 percent range, the likelihood of a crash was at least nine times greater than at zero BAC for all age groups. Younger drivers with BACs in the 0.05-0.09 range had higher relative risks than older drivers, and females had higher relative risks than males. At very high BACs (at or above 0.15 percent), the risk of crashing was 300 to 600 times the risk at zero or near-zero BACs. These relative risk estimates are considerably higher than estimated in other studies, but other studies have based their estimates on all crashes rather than single-vehicle crashes only. In this study, relative risks were also lower when based on driver fatalities in all crashes. However, when plausible assumptions were made about the BAC distributions of other participants in multiple-vehicle crashes (whose actual BAC is often unknown), the relative risks based on the maximum BAC of the crash participants were nearly as high as those estimated in single-vehicle crashes. PMID- 1875702 TI - Differences between roadside and subsequent evidential breath alcohol results and their forensic significance. AB - Breath alcohol measurements for forensic purposes are typically not made at the time of a driving incident but at some later time. Therefore, the magnitude of variation in breath alcohol concentration (BrAC) following the time of arrest is of concern. The use of roadside preliminary breath test (PBT) instruments can provide data on BrAC closer to the time of a driving incident and allow for comparison with later evidential analysis. This retrospective study evaluates two distributions (N = 968): differences between PBT results and the first evidential breath test (PBT-BrAC1) and differences between two (duplicate) evidential breath alcohol tests (BrAC1-BrAC2). The two distributions were shown to vary from each other and from the normal with statistical significance (p less than .05). The PBT-BrAC1 distribution had greater variability (SD = .025) than the BrAC1-BrAC2 distribution (SD = .010). An important result was that the PBT was equal to (within duplicate sampling variability) or greater than BrAC1 in approximately 85.5% of the cases. The remaining 14.5% could not be explained by sampling variability within the duplicate test distribution. The variability in both distributions typically exceeds the normally accepted alcohol elimination rates. The conclusion is that differences between roadside and subsequent evidential breath results cannot be attributed solely to absorption or elimination kinetics. Intra-individual breath sample differences can be large and thus obscure the accurate evaluation of absorption and elimination rates. Breath tests conducted within approximately 2 hours of driving will reflect, within experimental uncertainty, the BrAC at the time of driving. PMID- 1875703 TI - The prevalence of antisocial behavior among U.S. Army DWI offenders. AB - This study compares arrest records for three groups of male soldiers. The first group of 76 had been arrested for DWI, completed a 5-day, in-patient evaluation/education program and were subsequently re-arrested, all within the period from January 1985 through December 1987. The second group of 76 was composed of a random sample, matched by age and ethnicity who had completed the 5 day program following a DWI but had not been re-arrested. The third group was a control group of 76, matched by age and ethnicity, but with no record of DWI, who were randomly selected from the same military units as the initial two groups. Soldiers with one DWI had significantly more arrests than did soldiers in the control group; soldiers with two DWI arrests had significantly more arrests than either of the other groups. The data indicate that soldiers apprehended for DWI are more likely than non-arrestees to be arrested for a wide variety of antisocial behaviors. PMID- 1875704 TI - Attitudes toward alcoholism among psychologists and marriage, family and child counselors. AB - This study examines the attitudes of 589 randomly chosen licensed California psychologists and marriage, family and child counselors toward alcoholism. Their anonymous replies revealed that the two professional groups were relatively homogeneous in nature. The majority of each subscribed to the disease concept of alcoholism, recognized the importance of abstinence in problem resolution and as a treatment goal, rejected insight as a prerequisite of sobriety, believed in a positive prognosis and were extremely willing to be involved in the treatment of alcoholics. Negative attitudes toward alcoholics were expressed with respect to attribution of responsibility and a persistence of stigmatization of the alcoholic. PMID- 1875705 TI - Gender-specific drinking styles in alcoholics and nonalcoholics. AB - This study examined sex differences in drinking style when considering both alcoholics and nonalcoholics (controls). The Alcohol Use Inventory was employed as a descriptive instrument. Of the 16 primary scales two results of significant interaction were obtained indicating sex differences in problem drinking practices corrected, as it were, for sex differences in normal drinking practices. Female alcoholics used alcohol to alter their mood more than did the alcoholic men, whereas women in the control group used it less for this purpose than did the male controls. The second interaction effect indicated that female alcoholics drank in response to marital difficulties much more than did male alcoholics. The control women, by contrast, demonstrated less of a likelihood to drink for this reason than did male controls. PMID- 1875706 TI - Personality characteristics of alcoholic fathers and their sons. AB - Recovering alcoholic fathers with a positive family history of alcoholism and their 10-15 year-old sons were assessed on a variety of personality measures and compared to a matched group of nonalcoholic fathers with a negative family history of alcoholism, and their sons. Assessment instruments for the sons included the Personality Inventory for Children, High School Personality Questionnaire, Junior Eysenck Personality Inventory and the Tridimensional Personality Questionnaire. Comparable questionnaires were administered to the fathers: the MMPI, 16 Personality Factor Questionnaire, Eysenck Personality Inventory and the Tridimensional Personality Questionnaire. No psychopathology or extreme personality variants were observed in either fathers' or sons' groups. However, MANOVAS and linear discriminant functions revealed significant differences on several personality measures between fathers' and sons' groups. Compared to sons of nonalcoholics, sons of alcoholics were relatively more compulsive, insecure and fearful while being more subdued and detached. The recovering alcoholics were more impulsive and regimented than the nonalcoholics. An index resulting from the combination of the best personality discriminators was significantly correlated in father-son pairs. In addition, this index was significantly correlated with key neurocognitive variables from our previous study which assessed the same father-son pairs. This atypical CNS profile, encompassing altered electrophysiology, neuropsychological performance and personality traits, may be useful in identifying those at increased risk for developing alcoholism. PMID- 1875707 TI - Drinking among subgroups in the adult population of New York State: a classification analysis using CART. AB - Using data from a representative sample of 5,952 adults in New York State, CART (Classification and Regression Trees) methodology was used to classify abstainers and drinkers according to interactions among 10 sociodemographic characteristics. A CART analysis classifying abstainers versus drinkers selected income at $25,000 for the initial split with high rates of drinking among higher income individuals. Low rates of drinking were shown for low income women with less than a high school education. A second CART analysis was performed for drinkers only, revealing a number of subgroups of heavier drinkers, including non-Jewish, non Oriental men under 35 years old and never-married or divorced minority women over the age of 24. PMID- 1875708 TI - The inheritance of alcohol consumption patterns in a general population twin sample: I. Multidimensional scaling of quantity/frequency data. AB - Quantity/frequency data on alcohol consumption were obtained by mailed questionnaire from 2,903 same-sex monozygotic and dizygotic Australian twin pairs. Nonmetric multidimensional scaling was applied to these data. A three dimensional solution was required to account for the observed pattern of twin concordances for alcohol consumption. These results suggest separate determination of abstinence, frequency of consumption and quantity consumed when drinking, rather than inheritance of a single continuum of overall consumption level. PMID- 1875709 TI - Development of a "Steps Questionnaire". AB - Thousands of men and women have begun their recovery from alcoholism through the support of Alcoholics Anonymous (AA) and its well-known "12-Step" program. The purpose of the present study was to develop a scale to measure alcoholics' levels of agreement with the first three of AA's 12 Steps and to test the relationship between sobriety and belief in these three steps. Using both factor analysis and Rasch analysis, two versions of a "Steps Questionnaire" were developed. A 96 member subset of the original subject pool was assessed quarterly for 1 year following inpatient treatment to determine the predictive validity of the questionnaire. The results of this study suggested that agreement with AA's first three steps can be measured and that agreement with AA's first step correlates with number of sober days posttreatment. The dichotomization of Steps Questionnaire scores into total agreement versus partial agreement with Step 1, and from this the reduction of uncertainty in the prediction of abstention over a lengthy follow-up period, provides support for AA's contention that total surrender to one's powerlessness over alcohol is part of the process of achieving abstention. PMID- 1875710 TI - Reductions in cirrhosis deaths in the United States: associations with per capita consumption and AA membership. AB - Cirrhosis mortality and morbidity rates have declined in many jurisdictions, including the U.S., in recent years. Previous research in Canada and Europe suggests that these declines are linked to changes in per capita consumption of alcohol and changes in the availability and/or utilization of services to reduce abusive drinking (e.g., treatment, Alcoholics Anonymous). In this study, changes in cirrhosis death rates in the 50 U.S. states and the District of Columbia between 1974 and 1983 were regressed onto changes in per capita consumption (1974 83). AA membership (1974-83) and alcoholism treatment (1979-82). No significant relationship between treatment and cirrhosis changes was observed; however, the measure of change in treatment may not reflect the full extent of changes that occurred in the 1974-83 period. As predicted, decreases in per capita consumption and increases in AA membership were significantly associated with decreases in cirrhosis rates. PMID- 1875711 TI - Specifying the relationship between alcohol use and cognitive loss: the effects of frequency of consumption and psychological distress. AB - Previous research has found a relationship between increased quantity of alcohol usually consumed per drinking occasion and decreased sober cognitive performance. It has been suggested that the effects of quantity of alcohol consumed may be conditional upon the frequency of alcohol use and that decreased performance in social drinkers may be a consequence of psychological distress (i.e., anxiety and depression). An analysis of data from a representative sample of employed men and women in metropolitan Detroit indicates that the relation between quantity of alcohol consumed per occasion and abstraction performance is conditional upon the frequency of alcohol use but that the relationship cannot be accounted for by psychological distress. PMID- 1875712 TI - Hemodynamic effects of a single moderate dose of alcohol in elderly subjects. AB - The effects of 0.5 g ethanol/kg body weight and of an iso-volumic control drink were compared in eight normotensive subjects aged 70-96 years. Blood alcohol concentration reached a mean (+/- SEM) maximum of 44.4 +/- 5.0 mg/dl at 50 minutes after the start of drinking. Compared to control, alcohol increased mean sitting and standing heart rates by 3.4 +/- 1.3 (p = .08) and 5.4 +/- 1.9 (p less than .05) beats/minute, respectively; mean venous haematocrit rose by 3.9 +/- 1.3% (p less than .05). There were no significant changes in sitting or standing systolic or diastolic blood pressures after alcohol compared to the control drink. A single moderate dose of alcohol has only minor haemodynamic effects in normotensive elderly subjects. The rise in heart rate after alcohol may be a reflex response that helps to maintain blood pressure in the face of reduced circulating plasma volume due to alcohol-induced diuresis. PMID- 1875713 TI - [Pregnancy and labor in women over 40 years of age]. AB - During the 1970-1989 period, there were 23,915 deliveries of which 278 (1.16%) occurred in women 40 years of age or older. The latter included 62 (22.3%) primiparas, 158 (56.8%) pluriparas and 58 (20.9%) multiparas. The control group consisted of 14,400 women 20-34 years of age (50% primiparas and 50% pluriparas) from the same period. There was no antenatal visit in 9.4% of the women 40 years of age or older. This group included more housewives, more unmarried women and more women with previous spontaneous and induced abortions than the control group (P less than 0.05). Threatened abortion (16.2%), EPH gestosis (22.3%), impaired glucose tolerance (8.3%), gestational diabetes (7.2%), delivery before 37 weeks (11.5%), delivery after 42 weeks (3.6%), premature rupture of the membranes (18.3%), meconium-stained amniotic fluid (19.8%), elective caesarean section (11.5%), caesarean section delivery (16.5%), vacuum extraction (4.7%), placental lysis or uterine exploration (4.3%) were more frequent in the study than in the control group (P less than 0.05). There were more cases with episiotomy (P less than 0.001) in the control group, whereas there were no differences as regards cervical cerclage, weight gain above 14kg, breech presentation, transverse presentation and assisted breech delivery between the two groups (P greater than 0.05). There was no case of uterine rupture or maternal death either in the study or the control group. The authors conclude that a woman 40 years of age and older is in an advanced age for pregnancy and delivery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875714 TI - [T lymphocyte subpopulations in women with spontaneous abortions]. AB - Investigations were carried out to observe changes in the functional T-lymphocyte activity, as well as the presence of single T-lymphocyte subpopulations in the first trimester of pregnancy in 10 pregnant women with recurrent abortions in their previous pregnancies, compared to 8 healthy pregnant women in the first trimester and 20 of them in the third trimester of pregnancy, and in 30 healthy nonpregnant women at the fertile age. The functional T-lymphocyte activity (PHA test) was decreased in pregnant women with recurrent abortions (54 +/- 0.99) and in healthy pregnant women (56 +/- 2.50) compared to healthy nonpregnant women (76 +/- 4.80). The total number of lymphocytes in the first trimester was decreased in the investigated group (22 +/- 5.38) and also in healthy pregnant women (25 +/ 1.55) in relation to nonpregnant women (33 +/- 3.15). The percentage of T lymphocytes was similar (59 +/- 4.32 and 58 +/- 1.96 in relation to 80 +/- 2.80). Helper T-lymphocytes (T-4) were significantly decreased in the investigated group (28 +/- 4.25) compared to the group of healthy pregnant women in the first trimester (32 +/- 1.60) and healthy nonpregnant women (55 +/- 2.37). Suppression T-lymphocytes (T-8) were significantly increased in the investigated group (30 +/ 3.11) in relation to healthy pregnant women in the first trimester (25 +/- 2.45) and to healthy nonpregnant women (23 +/- 1.95). The ratio of helper T-lymphocytes and suppression T-lymphocytes (T4:T8) was significantly lower in pregnant women with recurrent abortions compared to healthy pregnant women in the first trimester and to healthy nonpregnant women. PMID- 1875715 TI - [Development of peritubular myoid cells in the rat testis]. AB - In the testes of 47 embryos, fetuses and newborn rats (Fisher strain), until the 15th day of life, the appearance and numerical dynamics of "premyoid" and myoid cells were analysed by light microscopy. The material was prepared routinely (fixed in Bouin fluid, embedded in paraffin, and cut to the thickness of 7 micrometers). The embryos of the 12th to 17th day of gestation were serially sectioned in toto, while fetal testes on the 18th to 21th day of gestation were removed and serially cut as well as the rat testes after birth. In each testis ten seminiferous tubules (cords) sectioned perpendicularly were analysed and only in two testes was it possible to find out nine but not ten perpendicularly sectioned tubules. Until the first week after birth, the lengthened cells that envelope tubules (cords) are called "premyoid". In the second half of the second week two types of lengthened cells in the envelope could be seen: one with a very thin, dark nucleus and the other with a lighter and thicker nucleus located peripherally, toward the interstitium. The former are considered myoid cells and the latter as fibroblasts. The numerical dynamics of "premyoid" and myoid cells evidently depends on the "pulsatile" effect of gondotropins. In the prenatal period, it was possible to see two increases in the number of these cells: on the 16th and on the 20th day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875716 TI - [Epilepsy and pregnancy]. AB - A total of 132 women with epilepsy were confined in the period from 1978-1989. Their pregnancies and outcomes were analysed. The special aim was to find out if the anticonvulsive therapy has any correlation with the occurrence of fetal malformations in the studied group of women. In 43.9% of pregnant women with epilepsy, methyl-phenobarbitone as an anticonvulsive drug was administered, while carbamazepine was applied in 13.6% cases. A combination of phenytoin and phenobarbitone was prescribed in 18.9% of cases. Primidone was the drug of choice in 8% cases and 5.3% of patients were treated with various combinations of anticonvulsive drugs. Hyperemesis, threatened spontaneous abortion and premature labor complicated significantly more pregnancies in patients with epilepsy than on controls. Pregnancies from the studied group were terminated by the cesarean section in significantly more cases (11.2%) than in the control group (5.4%). Newborns from mothers with epilepsy had a statistically lower birthweight (3173 +/- 575 g) than those born from healthy mothers (3376 +/- 510g). Fifteen newborns or 11.2% were born with congenital malformations, while among the control group of newborns only two were malformed. It is noticed that the newborns from mothers treated with phenitoin and phenobarbitone had dysmorphic anomalies of the face more frequently. The drugs mentioned above interfere with the metabolism of K vitamin and as a result of this interreaction, mothers and newborns can suffer from coagulation disorders. In conclusion it is important to mention that no anticonvulsant drug seems to be absolutely safe when used during pregnancy since each of them has a teratogenic effect on the fetus. PMID- 1875717 TI - [Characteristics of cancer of the female reproductive organs as observed at the Gynecology-Obstetrical Department of the Osijek General Hospital]. AB - In the 1980-1989 period, 671 women were diagnosed with a malignant tumour of reproductive organs at the Department of Gynaecology, Cervical cancer proved most frequent, with 46.5% of the cases, followed by the cancer of the uterine body occurring in 29.5% of the patients. In 18.8% of the women, ovarian and oviductal cancer was diagnosed, whereas vulvar and vaginal cancer was found in 5.5% of the cases. There were 76.1% of the patients older than 50 years. Nulliparas suffered from ovarian and uterine body cancer significantly more often than from cervical cancer (t = 3.794; p less than 0.001, i.e. t = 2.974; p less than 0.001). However, terti- or multiparas had cervical cancer significantly more often than the cancer of ovaries or the uterine body (t = 3.711; p less than 0.001, i.e. t = 3.000; p less than 0.01). The first stage ovarian cancer was diagnosed in 15.0% of women only, whereas 37.1% of cervical and 78.3% of uterine body cancers were discovered at the first stage. At the time of diagnosis, the mean age of the patients with cervical cancer was 55.8 years, with ovarian cancer 57.9 years, with oviductal cancer 57.3 years, with uterine body cancer 60.8 years and with vulvar cancer 71.7 years. There were 34% of cervical cancer patients at the premenopausal age 15.5% with uterine body cancer and 27.5% of those suffering from ovarian cancer. The general five-year survival rate for patients suffering from the cancer of reproductive organs was 40.6%, i.e. 40.5% for cervical cancer, 54.7% for uterine body cancer, 23.4% for ovarian and oviductal cancer and 17.7% for vulvar or vaginal cancer. The total of 25% of the patients were lost from the evidence. PMID- 1875718 TI - [T lymphocytes, non-malignant and premalignant changes in the planocellular epithelium of the uterine cervix]. AB - T lymphocytes play an important role in the immune response to both neoplasia and viral infection. Normally, about 60% of T lymphocytes in the peripheral blood are T4 (helper) lymphocytes, while 20-30% are T8(suppressor) lymphocytes. When this ratio is inverted, most significant changes occur. The aim of the study was to examine the T4/T8 lymphocyte ratio in the peripheral blood of patients with nonmalignant and premalignant changes of the cervical epithelium and to compare it with that in patients without any cytological or colposcopical cervical abnormality. The results show a significant decrease of the T4/T8 lymphocyte ratio in the peripheral blood of patients with leukokeratosis (1.55) and especially of those with cervical intraepithelial neoplasia (1.19), compared with the results of the control group (2.31). These findings, as well as the knowledge of the importance of immune response in the control of the onset of malignancy, that the determination of T4/T8 lymphocyte ratio might be helpful in the prediction of the degree of premalignant cervical chance and indicate patient's follow-up. PMID- 1875719 TI - [Pregnancy outcome after conization]. AB - The outcome of pregnancy in 68 women with previously made conisation of the uterine cervix is presented. As a control group were 68 pregnancies which were the first in the protocol following the examined ones. Of 68 women of observed group there were 45 (66.2%) term deliveries, 10 (14.7%) preterm deliveries, and 13 (19.1%) spontaneous abortions, while in women of control group the results were 52 (76.5%), 6 (8.8%) and 10 (14.7%) respectively. This did not represent a statistical significance (chi 2 = 1.89; p less than 0.05). In the first desired pregnancy after conisation 43 (63.2%) women were resting in bed and taking medicaments, 20 (29.4%) had cervical cerclage, while in women of the control group there were 14 (20.6%) and 5 (7.4%), respective what represents statistically significant difference (chi 2 = 25.4; p less than 0.01; chi 2 = 11.3; df = 1, p less than 0.01). Of 43 women of observed group with resting and medicaments in pregnancy 33 (76.7%) had term deliveries, 8 (18.6%) preterm deliveries and 2 (4.7%) spontaneous abortions, while in 25 women without resting and no medicaments, the results were 13 (52%), 11 (44%), 1 (4%) respectively. This represents statistical significant difference (chi 2 = 4.42; p less than 0.05). In the control group of 54 women without resting and no medicaments, there were 45 (83.3%) term deliveries, 3 (5.6%) preterm deliveries and 6 (11.1%) spontaneous abortions, while in 25 women after conisation and no resting there were 13 (52%), 11 (44%), 1 (4%) respectively. This represents a statistical significance (chi 2 = 8.59; p less than 0.01). (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875720 TI - [Results of the IVF/GIFT program in Maribor]. AB - The results of the IVF/GIFT programme for 1989 in Maribor are presented. During this period 4 clinical pregnancies were attended by the IVF procedure and one by GIFT and ZIFT each. In the IVF procedure the highest percentage of pregnancies was obtained in the group of women with the tubal factor of infertility (n = 34) where 4 clinical pregnancies on 22 ET were registered (18.1%). Cycle synchronisation with contraceptives, followed by stimulation with CC-HMG proved to be the most successful protocol for the cycle stimulation. With this protocol, pregnancy was attained in 4 of 19 stimulated cycles (21.0%). In the spontaneous cycles (n = 17) no pregnancy was registered. PMID- 1875721 TI - [Malignant melanoma arising from a cystic dermoid teratoma of the ovary]. AB - The primary malignant melanoma of the ovary is a rare kind of neoplasm. This one is in the world literature the eleventh well-documented case having developed in the ovary of a 66-year-old woman. A unilateral ovarian teratoma was removed, within which a malignant melanoma was found. The junctional activity of melanocytes was demonstrated in the epidermis within the teratoma. An extraovarian primary melanoma was not observed. The patient was treated with a bilateral adnexectomy and hysterectomy. PMID- 1875722 TI - [Recurrent adenocarcinoma of the uterus]. AB - In a 60-year-old woman because of postmenopausal haemorrhage diagnostic curettage was performed. The histopathologic finding was the adenocarcinoma of the endometrium. The clinical stage was Ib, grade 2 or respectively presumptive stage IV with regard to ultrasound and radiographic findings. After radical hysterectomy and the resection of the sigmoid colon, chemotherapy with cytostatics was applied for 6 months. Three months after chemotherapy the recurrence of the tumour in the vaginal formix and superficial inguinal lymph nodes metastases appeared. Colpectomy with the extirpation of vaginal carcinoma and inguinal lymphadenectomy were performed, followed by irradiation. The course of the disease has shown that when the cancer is located near the point of entry of the uterine tube, the diagnosis and, if needed, therapy should be extended to inguinal regions too. PMID- 1875723 TI - [Electromyography of the uterus in monitoring pregnancies with symptoms of premature labor]. AB - Characteristics of uterine muscle action potentials in 100 gravidas with symptoms of preterm labor or imminent abortion (presence of contractions with cervical changes) from 18th till the 32nd weeks of pregnancy are analysed. Twenty four gravidas with uncomplicated pregnancy were monitored electromyographically from the 20th weeks until term, once a week. There was low electrical activity in uncomplicated pregnancies up to 7 days before labor. A similar trend was observed in pregnancies that were finished before term. But, in symptomatic pregnancies finished preterm, the index of uterine muscle electrical activity (expressed in the percentage of voltage plus frequency) was continuously, although not significantly, above the values in symptomatic and asymptomatic term pregnancies. In only 2 out of 18 (11.1%) before term terminated pregnancies and in 45 out of 82 (54.9%) in term accomplished pregnancies, was electrical silence was registered during clinical symptoms (p less than 0.01). In preterm accomplished pregnancies, higher voltages and more frequent occurrence of biphasic and polyphasic spikes were registered (p less than 0.05), although the single parameter was of no prognostic significance. With a successful tocolytic treatment, the index of uterine muscle electrical activity was significantly reduced (from 57.16 to 20.86, t = 2.52, p less than 0.02) and was similar to that registered in symptomatic term pregnancies subjected to no tocolytic treatment. Although intravenous tocolysis was shown diminish voltage and frequency, in preterm delivered pregnancies no reduction in electrical activity was observed. Uterine electromyography could be used as a predictor of successful or unsuccessful tocolytic treatment. PMID- 1875724 TI - Differential age-dependent attenuation of reflex tachycardia by verapamil in rats. AB - To determine if verapamil alters baroreflex function differently depending on age, reflex heart rate responses to intravenous infusions of phenylephrine or sodium nitroprusside were compared in conscious 5- and 14-month-old rats before and after daily oral administration of verapamil (100 mg/kg) for 6 days. The effects of verapamil on parasympathetic and sympathetic mediation of heart rate were also assessed by repeating baroreflex tests after treatment with either propranolol or atropine. All reflex heart rate responses were initially smaller in 14- than in 5-month-old rats. Regardless of age, magnitude of reflex bradycardia or the effects on it of either cholinergic or beta-adrenergic blockade, were unaffected by verapamil. By contrast, reflex tachycardia which was attenuated in both age groups, was decreased further by subsequent cholinergic or beta-adrenergic blockade in 5-month-old rats, but only by cholinergic blockade in 14-month-old rats. These findings suggest that while verapamil did not affect autonomic mediation of reflex bradycardia, it reduced that of reflex tachycardia differently depending on age. Whereas it attenuated both sympathetic and parasympathetic mediation of reflex tachycardia in 5-month-old rats, it attenuated only sympathetic mediation in 14-month-old rats. PMID- 1875725 TI - Effects of age on diabetes- and insulin-induced changes in pancreatic levels of alpha-amylase and its mRNA. AB - During aging, protein synthesis undergoes decremental changes in many organs and tissues. In the pancreas, as well as in other exocrine glands, the rate of protein synthesis declines with age. However, it is unknown whether this decline is related to intrinsic aging changes which affect the secretory cell function. In this study, we compared the ability of pancreatic acinar cells to synthesize amylase and its messenger RNA (mRNA) in response to insulin treatment of young and old rats rendered diabetic with streptozotocin (STZ). In STZ-induced diabetic rats, amylase protein and its mRNA levels were reduced drastically in the pancreas of young and old groups. Injections of these diabetic rats with insulin increased pancreatic amylase mRNA contents significantly in both young and old rats. Insulin also increased proportions of amylase protein synthesis in the pancreas of both age groups. These results indicate that the pancreatic cells remain effective during aging in their transcriptional activity for functional amylase mRNA in response to an exogenous stimulus of insulin. PMID- 1875726 TI - Endurance-training induced changes in skeletal muscle phosphoglycerate kinase of old Wistar rats. AB - Sufficiently intense, long-term, endurance training has been shown in several studies to induce a variety of adaptations in skeletal muscle, including a substantial restoration of the activities of several muscle enzymes which are known to be modified during biological aging. This activity-restoration may reflect either an increase in the amounts of enzyme proteins or an enhancement of the specific activities of these molecules. The present study examined the effect of long-term endurance training on the status of phosphoglycerate kinase in skeletal muscle of old rats, as compared with the enzyme isolated either from non trained old or young animals. The kinetics of heat inactivation, which differ markedly between young and old forms of phosphoglycerate kinase, were used as a sensitive probe for the status of the enzyme. The results reveal a remarkable similarity between the heat inactivation patterns of phosphoglycerate kinase from the muscle of old, exercise-trained rats and enzyme purified from young animals, while enzyme samples isolated from sedentary old animals are significantly more heat-stable. Adaptation to endurance-training is thus evident at the molecular level, and maintains phosphoglycerate kinase in its young form. The aging of this enzyme has been previously shown to involve only conformational changes, which develop following a reversible partial oxidation of reactive cysteine residues. Whether the adaptation of the enzyme to endurance-training results from enhancement in its turnover rate (i.e., dwell time in the cell becoming too short for modifications to develop) or is due to increased protection against oxidation (being the first step in the enzyme's aging) remains to be studied. PMID- 1875727 TI - Blood-nerve and blood-brain barrier permeabilities and nerve vascular space in Fischer-344 rats of different ages. AB - The permeability-surface area product (PA) of [3H]- or [14C]sucrose at the blood nerve barrier (BNB) of the sciatic nerve; and at the blood-brain barrier (BBB), were determined in Fischer-344 rats at 3, 11 and 31 months of age. PA was determined by using an in vivo i.v. bolus injection of radiotracer with two-time point graphic and quantitative autoradiographic methods. Vascular space and water content of the tibial nerve of these rats also were determined using quantitative morphometry and dry and wet weight ratios, respectively. There was no significant difference between mean PA(BNB) in any age group [(PA(BNB) at 3 months = 1.2 +/- 0.1 (mean +/- S.E.), at 11 months = 1.8 +/- 0.3; and at 31 months = 1.4 +/- 0.2 x 10(5) ml/s . g wet wt; n = 5-8 rats], nor any difference in PA(BBB). The mean ratio (%) of surface area of endoneurial blood vessels/nerve cross-section of the tibial nerve also did not differ between any group [3 months: 16 +/- 2 vessels; mean surface area ratios = 2.20 +/- 0.10%, n = 5; 11 months: 22 +/- 3 vessels and 2.48 +/- 0.21%, n = 5; 11 months: 22 +/- 3 vessels and 2.48 +/- 0.21%, n = 5; and at 31 months: 26 +/- 1 vessels and 2.40 +/- 0.23%, n = 4). The mean nerve water in rats at 31 months was 64.8 +/- 1.1% wet wt and did not differ from that at 11 months (66.0 +/- 0.6% wet wt) or at 3 months (65.1 +/- 1.0% wet wt) (n = 5-8 nerves). Our results indicate that BBB and BNB integrities are not altered in senescent Fischer-344 rats. PMID- 1875728 TI - Supplemental growth hormone alters body composition, muscle protein metabolism and serum lipids in fit adults: characterization of dose-dependent and response recovery effects. AB - Using double-blind, placebo-controlled procedures, the effects of low and high therapeutic dosages of methionyl-human growth hormone (met-hGH) on body composition, muscle protein metabolism and serum lipids were studied in 7 fit adults without growth hormone (GH) deficiency. Dose-dependent changes in body composition were observed that in part appeared to be influenced by a response recovery effect, as measured by responses factored according to the duration of washout between exposure to the low and high dosages of met-hGH (6 weeks vs. 12 weeks vs. 18 weeks). Increases in fat-free weight were accompanied by an increase in skeletal muscle protein metabolism. Basal levels of cholesterol were inversely related to peak levels of GH in response to exercise stimulation and IGF-I, while GH supplementation lowered levels of total cholesterol and high- and low-density lipoproteins. A dose-dependent effect occurred for total cholesterol, and the percent change in cholesterol was related to the percent change in insulin-like growth factor I (IGF-I). Endogenous levels of GH were attenuated in response to stimulation and IGF-I levels were increased after treatment with GH, but no dose dependent changes were observed. We conclude that met-hGH alters body composition and muscle protein metabolism, and decreases stored and circulating lipids in fit adults with a pre-existing supranormal body composition. The physiological profile of the person was not as important as the treatment conditions in determining the somatic and physiological response outcomes. PMID- 1875729 TI - Exposure to estradiol impairs luteinizing hormone function during aging. AB - The loss of ovulatory cyclicity in many mammals is caused by changes in the hypothalamic-pituitary (H-P) control of the preovulatory luteinizing hormone (LH) surge. This work evaluated the anterior pituitary (AP) component of the H-P axis by determining the ability of perifused AP to release LH following sustained but pulsatile LHRH stimulation. The normal dual discharge profile of LH was affected by age. The first hour of the response, unaffected by cycloheximide, was similar in 5-6-month-old (mature), 12-13-month-old (declining litters) and 16-18-month old (irregularly cycling) mice. The remaining protein synthesis-dependent part of the response was reduced in the 16-18 and 22-24-month-old (anestrus) mice. The role of estradiol (E2) in AP aging was further tested as AP from ovariectomized (OVXed) mice, deprived of E2 since puberty, responded as well as the mature proestrous group. In contrast, aged mice subjected to long-term E2 exposure (cycling or OVXed plus E2 replacement) failed to produce the dual response pattern. Since alterations in LH response occurred during the protein-dependent phase, synthetic processes that involve packaging and transport of stored LH, or the production of new LH, may be affected by age. Furthermore, E2 is a major factor in altering LH function and appears to act before middle age. PMID- 1875731 TI - Effects of aging on the induction of experimental systemic lupus erythematosus (SLE) in mice. AB - The study was designed to determine whether manifestations of autoimmunity are altered with age, using an experimental model in which systemic lupus erythematosus (SLE) is induced in mice. Young (2-month-old), and aging (18-month old) BALB/c female mice were immunized with a human monoclonal anti-DNA antibody that bears a common idiotype (16/6 Id). Control groups were either left untreated or were injected with human IgM (HIgM). Anti-16/6 Id levels were found to be significantly lower in the old mice than in the young. Similarly, anti-anti-16/6 Id (murine 16/6 Id+) values were lower in the old. Mice injected with the 16/6 Id also produced various autoantibodies, including anti-dsDNA, anti-RNP, anti-Sm and anti-histones antibodies. The levels of these antibodies were lower in the old mice than in the young, yet the differences were not statistically significant. Levels of autoantibodies examined in control animals were either similar in both age groups (anti-RNP and histones) or lower in the old (anti-dsDNA and Sm). Four months after a booster injection of 16/6 Id, the young mice developed clinical manifestations of SLE, including proteinuria and leukopenia, which were seen, in milder form, in the aged mice. Immune complex depositions examined by immunohistology on kidney sections suggested similar differences based on the age of the animals. Our results suggest that aging might actually be associated with a decline in the capacity to produce autoimmune responses. PMID- 1875730 TI - The influence of age on the healing of normal and ischemic incisional skin wounds. AB - Experimental studies have not shown that the 'common' clinical experience, which suggests that wound healing is impaired in an old organism, is valid for healthy old experimental animals. We have developed a model in the rat for ischemic wound healing by using an H-shaped double skin flap, where the test wound is the horizontal line in the H. Our previous studies have shown that the blood flow in this wound is only 7% of that of a normally vascularized wound on the first postoperative day. Functional (biomechanical) properties of this wound are decreased by up to 67% after 10 days of healing and certain key properties by up to 64% after both 10 and 20 days. This study reports on the effect of aging, using 3- and 24-month-old rats. The 'normal' incisional wounds healed equally well in both groups. On the other hand, the ischemic wounds in the old animals were found to be impaired by 40-65% compared to similar wounds in the young animals. It is concluded that ischemia is deleterious for wound healing in old age and that one of the key elements of the clinical experience of impaired wound healing in old age is probably based on concomitant diseases in old patients, contributing to varying degrees of ischemia in the traumatized tissue. PMID- 1875732 TI - Effect of thymic hormone treatment on several immune functions of nude mice. AB - Studies of the effect of short-term, intense treatment with thymic hormone on mitogen response, cytotoxicity to EL-4 lymphoma and natural killer cell (NK) activity was investigated Balb/c nude mice (about 12-16-week-old) were treated 5 times per week for 3 weeks with: Facteur Thymic Serique (FTS) and Thymopentin (TP5, Thymopoietin 32-36) at 1 microgram and 10 ng; TM4 1 ng (an enzyme resistant variant of FTS); Thymosin Fraction V (TF5), 10 and 1 microgram; and 0.1 ml saline, and killed 2 days after the last treatment. The animals were monitored for changes in weight, hematocrit, peripheral blood lymphocyte (PBL) and spleen mitogen response. Additional groups of nude mice were immunized with 1 x 10(7) 5000 R irradiated EL-4 cells 10 days before sacrifice and tested for the presence of cytotoxic T-lymphocytes (CTL). The results show that weight and hematocrit were similar among the groups. Treatment with FTS significantly elevated the number of PBL. Spleen stimulation in mice treated with 1 microgram TP5 was depressed to mitogen concanavalin A (ConA) and lipopolysaccharide (LPS) stimulation. The phytohemagglutinin (PHA) response was not different among the treatment groups. The PBL mitogen response to ConA and LPS was generally increased over saline control in the hormone treated groups but was not statistically significant. The PHA response was only slightly elevated. No CTL was generated in nude mice in any of the groups. However, there was a statistically significant general depression of NK activity in all of the hormone treated animals compared with saline. The results indicate that the basic differentiation defect of the T-cells of nude mice cannot be restored to full functional activity by short-term treatment. PMID- 1875733 TI - Cell age dependent decay of human erythrocytes glutathione S-transferase. AB - Human red blood cells contain both glutathione S-transferase sigma (GST sigma) and glutathione S-transferase rho (GST rho). While the first isozyme does not change in red blood cell fractions of different mean density (age), GST rho, the main isozyme, shows a pronounced cell age dependent decay. Ion-exchange chromatographic experiments show that GST rho consists of only one isozymic form in young erythrocytes but is present in two components, with different electric charge, in mature and old cells. The "secondary" GST rho isozyme is more heat stable than the "primary" GST rho isozyme with the result that the total GST activity shows an apparent increase in heat stability during cell aging due to the formation of "secondary" isozymes. The kinetic properties and specificity of this enzyme do not show appreciable modifications during cell ageing. The data reported in this paper suggest that red blood cell aging is associated with a reduced detoxifying ability due to GST rho decay. PMID- 1875734 TI - Age influence on the thymic capacity to promote differentiation of T cells: induction of different composition of T cell subsets by aging thymus. AB - Three kinds of experiments were performed to see the differential effect of aging thymus on T cell differentiation in nude mice and thymectomized mice. In the experiment of thymus grafting into nude mice, the thymic capacity to promote T cell differentiation was the highest at newborn stage, and declined to 80% of the peak level at as early as 1 week of age. The level at 4 weeks of age was 50-60% of the peak level and did not greatly change thereafter with advancing age of thymus donors, up to 24 months of age. However, composition of T cell subsets differed with age of thymus graft; i.e. L3T4(CD4)+ T cells were more easily induced than Lyt-2(CD8)+ T cells by aging thymus, resulting in an increase of the ratio of L3T4+/Lyt-2+ T cells with advancing age of thymus donors. The decreased number of T cells and their subsets in the mice thymectomized at 4 weeks of age could be almost totally recovered by the grafting of newborn thymus, but less efficiently by the grafting of 24-month-old thymus. In the latter case again, L3T4+ T cells were more easily induced than Lyt-2+ T cells, resulting in an increase of the ratio of L3T4+/Lyt-2+ T cells by the grafting of the old thymus. In neonatal mice thymectomized 3 days after the birth, Lyt-2+ T cells were more severely affected than L3T4+ cells, resulting in high ratio of L3T4+/Lyt-2+ T cells. It was suggested that the capacity of the thymus to induce T cells started to decline as early as 1 week of age and did not greatly change between 4 weeks and 24 months of age. However, the composition of T cell subsets induced by the thymus changed with age, with preference for L3T4+ T cells over Lyt-2+ T cells. PMID- 1875736 TI - Deciding whether a new test/measure is useful. PMID- 1875735 TI - Effects of aging and caloric restriction on I-compounds in liver, kidney and white blood cell DNA of male Brown-Norway rats. AB - Rodent tissues display species-, strain-, sex- and tissue-specific adduct-like DNA modifications termed I-compounds, which increase with age, are modulated by diet and are presumably derived from indigenous metabolic intermediates. We have explored whether I-compounds are affected by caloric restriction, which is known to extend life span and retard age-related degenerative and neoplastic diseases. Male Brown-Norway rats were fed NIH-31 diet ad libitum (AL). Calorically restricted (CR) rats received 60% of AL consumption, starting at 3.5 months. DNA was analyzed by 32P-postlabeling at 1, 4, 8, 12, 16 and 24 months of age in liver, kidney and white blood cells. I-compounds in AL liver and kidney exhibited complex tissue specific profiles; I-compound levels increased with age, plateaued between 8 and 18 months depending on tissue and diet and were 8.7 (liver) and 27.4 (kidney) modifications in 10(8) nucleotides at 24 months, thereby exceeding the corresponding 1-month values by 3.7- and 16.6-fold. CR resulted in similar profiles but did not diminish age-related increases, rather I-compound levels in CR liver and kidney were increased by about 70% and 30% versus age-matched AL rats. White blood cells exhibited few I-compounds and at low levels; age-related increases were small overall but more pronounced in CR rats. Higher I-compound levels in CR animals, which were presumably a consequence of metabolic effects elicited by CR, thus correlated with extended life span and, therefore, may be beneficial, in agreement with previous findings showing an association between reduced I-compound levels and hepatocarcinogenesis as well as organ susceptibility to diseases. PMID- 1875737 TI - How fast are hospital prices really rising? AB - The hospital services component of the Consumer Price Index (CPI) measures the cost of hospital services to private patients paying list prices. It is, however, widely used as an estimate of the overall rate of inflation in hospital prices in spite of the fact that there are strong reasons to believe that it is inappropriate to use the CPI for this purpose. This is because: 1) A growing number of patients are enrolled in health maintenance organizations (HMOs) and preferred provider organizations (PPOs), which negotiate discounts from list prices; and 2) the size of the discounts may have been increasing. The potential result is a gap between the rate of inflation of list prices and the rate of inflation of actual prices paid in transactions. This study explores whether such a gap exists and determines its possible magnitude. In addition, parallel indices for list and actual prices are computed on the basis of data from California hospitals for fiscal years 1983-1988. The analysis suggests that list price inflation has greatly exceeded actual inflation--by a factor of two for recent years. These findings have broad implications for evaluating not only inflation but also the impact of cost containment strategies. PMID- 1875738 TI - Interval adherence to mammography screening guidelines. AB - The objectives of this research were to document adherence to mammography screening guidelines among women over 50 years of age and to investigate factors related to adherence. Selected sociodemographic variables--personal breast health history, provider-related variables, and medical care utilization--were studied. Data were collected through a random digit dial telephone survey of 693 women from two geographic areas. While 48% had had a mammogram in the last year, only 20% reported at least two recent mammograms at yearly intervals. Adherence was significantly associated with having a higher income, being white, being 51 to 64 years old and having had breast symptoms and/or a family history of breast cancer. Additionally, women who had a regular physician, higher frequency of clinical breast examination, and a recent physician visit were more adherent. Women enrolled in Health Maintenance Organizations (HMOs) and/or covered by commercial plans were more adherent than women with no insurance or with entitlement coverage only. These relationships were generally maintained in multivariate analysis. While this study is consistent with others that demonstrate increasing adoption of mammographic screening, it also illustrates that the goal of regular screening according to guidelines has yet to be achieved. PMID- 1875739 TI - Organizational assessment in intensive care units (ICUs): construct development, reliability, and validity of the ICU nurse-physician questionnaire. AB - Health Services Research has a growing need for reliable and valid measures of managerial practices and organizational processes. A national study of 42 intensive care units involving over 1,700 respondents provides evidence for the reliability and validity of a comprehensive set of measures related to leadership, organizational culture, communication, coordination, problem solving conflict management and team cohesiveness. The data also support the appropriateness of aggregating individual respondent data to the unit level. Implications for further research are discussed. PMID- 1875740 TI - Development of an instrument to measure job satisfaction among dentists. AB - Because of the rapid changes that have occurred in the dental profession, the Dentist Satisfaction Survey (DSS) was developed to assess both facet and overall job satisfaction among dentists. The DSS was administered to a sample of 558 California general dentists. The results suggest that the DSS is a practical, reliable, and valid measure of dentists' job satisfaction. Internal consistency reliability coefficients for all facet subscales and the overall job satisfaction scale ranged from 0.60-0.92. The DSS discriminated between groups of dentists known to have different levels of job satisfaction; dentists identified by dental society presidents as being very dissatisfied scored significantly differently in the hypothesized direction on the DSS. A high correlation (r = 0.68) was found between judges' independent ratings of dentists' satisfaction based on their open ended comments and DSS scores. While the majority of respondents were satisfied with most facets of their jobs, substantial variation was found among dentists in their levels of satisfaction. PMID- 1875741 TI - Perceived need for dental care among persons living with acquired immunodeficiency syndrome. AB - Compromised oral health holds significant implications for the general health of medically vulnerable, HIV infected individuals. Past studies have reported that these individuals frequently suffer from oral opportunistic infections and have a tendency to develop severe periodontal disease. This study extends past research by examining the prevalence of oral infections according to patient characteristics and by reporting, for the first time, the level of perceived dental need in a large, multi-site sample of individuals with symptomatic HIV disease. Data for this study come from a survey of 857 clients of the Robert Wood Johnson Foundation's AIDS Health Services Program in 9 U.S. cities. More respondents (52%) reported a need for dental care than for any other service need. Multivariate analysis showed that clients who were white, in low-income groups, used intravenous drugs, or had a past history of oral opportunistic infections were more likely to report dental need. Relations between age, gender, insurance status, or disease status and perceived need were statistically nonsignificant. Forty-seven percent of the clients reported they had an oral opportunistic infection, the second outcome variable examined in this study. Statistically significant differences (P less than 0.05) were found in the prevalence of oral opportunistic infections among race and disease severity groups. Whites and the more severely ill were more likely to report an infection than their respective counterparts. PMID- 1875742 TI - Rating journals in health care administration. The perceptions of program chairpersons. AB - The perceived quality of a journal is often a heavily weighted factor in the appraisal of faculty performance. We developed a listing of 53 prominent journals in the field of health care administration and surveyed the chairpersons of the 52 accredited graduate programs in the United States, Canada, and Puerto Rico, asking each to rate the level of achievement of a faculty member who published in each journal. Using the chi-square goodness-of-fit method for a multinomial experiment, we were able to identify six distinct "tiers" of journals and show a relationship between the subject category of a journal and its tier ranking. The implications of the study findings for faculty members are addressed, followed by a discussion of the data limitations and suggestions for future research. PMID- 1875743 TI - Contracting between public agencies and private psychiatric inpatient facilities. AB - Purchasing human services through contracts with private providers has become an increasingly common practice over the past 20 years. Using data from a national survey of psychiatric inpatient facilities, this paper examines the extent to which psychiatric units in privately controlled general hospitals and private psychiatric specialty hospitals (N = 611) participate in contractual arrangements to provide services to governmental bodies. It also examines how the likelihood of such a practice is affected by hospital characteristics (general or specialty, for profit or nonprofit) and features of hospitals' environments, including the competitiveness of the market for psychiatric inpatient care and the population's need for services in the hospital's county. The findings indicate that nonprofit psychiatric specialty hospitals were more likely than other types of hospitals to enter into such contracts, and that forces such as local competition and need for services were not predictors of such involvement. Contracting was shown to have a significant impact on the level of referrals a hospital accepted, but these levels were also affected by competition and need. Among hospitals with public contracts, referral acceptance from public agencies was unaffected by these factors, but they did have a significant effect on referral acceptance by hospitals without public contracts. These data suggest that public agencies contracting for services with private hospitals may represent a means by which "public sector" patients may gain access to private providers. Further, this mechanism may impose sufficient structure and regulation on the acceptance of such patients that many concerns of hospital administrators regarding patients who are costly and difficult to treat and discharge can be allayed. PMID- 1875744 TI - Comparison of psychiatric screening tests in a general medical setting using ROC analysis. AB - Receiver operating characteristic (ROC) analysis was used to evaluate the usefulness of three self-administered screening instruments in helping primary care physicians detect anxiety and depressive disorders. This research was secondary to an investigation of hypochondriasis. The three tests were the Whitely Index (WI), the Somatosensory Amplification Scale (SAS), and the Somatic Symptom Inventory (SSI). Participating subjects were 75 patients seen in a general medical clinic and diagnosed as being free of hypochondriasis by DSM-III R criteria. Psychiatric disorder was assessed with the Diagnostic Interview Schedule, version III-A. The three instruments delineated patients with depressive disorders versus no depressive disorders and patients with anxiety disorders versus no anxiety disorders. For depressive disorder, the areas under the curve (AUC) were 0.87, 0.75, and 0.82 for the WI, SAS, and SSI, respectively. For anxiety disorders the AUCs were 0.79, 0.76, and 0.74, respectively, for the three tests. Although the WI yielded slightly higher values, the areas under the ROC curves did not differ significantly among the three tests. Because of its relatively short length--13 items--it was concluded that the WI can be useful for screening primary care patients, both with respect to depressive and anxiety disorders. PMID- 1875745 TI - A health status questionnaire using 30 items from the Medical Outcomes Study. Preliminary validation in persons with early HIV infection. AB - Many current health status instruments either are too long to use in many acquired immune deficiency syndrome (AIDS) clinical trials or omit important concepts. In this study, human immunodeficiency virus (HIV)-relevant items developed for the Medical Outcomes Study (MOS) from subscales for cognitive function, energy/fatigue, health distress, and a single quality of life item were added to a portion of the MOS Short-form General Health Survey. The resulting 30 item questionnaire reliably and distinctly measured ten aspects of health and took less than 5 minutes to complete. To test its validity, this modified measure was used to compare the health of 73 subjects with asymptomatic HIV infection and 44 with early AIDS-related complex (ARC). Compared with ARC subjects, asymptomatic individuals reported superior overall health, less pain, and better physical function, role function, cognitive function, and quality of life (rank sum, P less than 0.02). Asymptomatic subjects' scores were higher on most subscales than the age-adjusted scores of MOS outpatients with hypertension, diabetes, recent myocardial infarction, or depression; ARC patients scored closest to hypertensive patients. This instrument, containing a subset of the MOS measures of health-related quality of life, may be a useful outcome measure for AIDS clinical trials. PMID- 1875746 TI - Practice variation in rheumatologists' encounters with their patients who have rheumatoid arthritis. AB - This article examines practice variation among rheumatologists in their use of time and procedures in follow-up outpatient encounters with rheumatoid arthritis patients. It focuses on differences across individual physicians rather than differences in populations of patients. In addition, the total variance is divided into parts due to patient characteristics, the providers' economic and other incentives to do procedures or reduce contact time, individual practice styles, and the random sampling of encounters. Data are taken from a stratified random sampling of U.S. rheumatologists. Analyses are based on 1,154 outpatient follow-up encounters with rheumatoid arthritis patients provided by 66 physicians, each of whom reported at least ten such encounters. There are large differences among the physicians in visit length, number of monitoring procedures used per encounter, and whether the encounter included measurements of complete blood count/urinalysis or erythrocyte sedimentation rate. Individual practice style differences are far more important causes of the variation that was observed among providers than are patient differences or practice incentive differences. It was determined that 5-40% of the cost of specific management activities could be saved by reducing the highest use. PMID- 1875747 TI - [International experts commented on the characteristics of perindopril, a new highly potent and well tolerated ACE. Perindopril has been able to reduce the thickness and rigidity of the arterial wall in animal studies]. PMID- 1875748 TI - [Protected bronchoalveolar lavage: a new endoscopic method in the diagnosis of bacterial pneumonia]. AB - BACKGROUND: The identification of causative microoganisms in severe pneumonias is a usually difficult problem. Protected brushing (PB) has a good specificity but a limited sensitivity. Conventional bronchoalveolar lavage (BAL-C) has an excellent sensitivity but a doubtful specificity. The investigation of a new technique such as the protected bronchoalveolar lavage (BAL-P) appears as logical, as it should combine the advantages of PB and BAL-C without their drawbacks. METHODS: In 15 patients without bacterial or fungal infections and in 23 with bacterial or fungal pneumonia, quantitative cultures were carried out in the samples obtained with PB, BAL-P and BAL-C. PB and BAL-C were performed with the usual technique. BAL-P was performed through the internal catheter of a telescoped double catheter with reabsorbable distal cap within the fibroscope channel. 40 ml of saline were instillated for the lavage. RESULTS: With BAL-P sensitivity was 95% and specificity 89%. These were, respectively, 55% and 94% with PB, and 95% and 42% with BAL-C. The technique of BAL-P was more complex an longer than that of PB. CONCLUSIONS: If these results are confirmed in further studies, BAL-P might become a method of choice for the bacterial pneumonias where now PB is indicated. However, in patients with hypersecretion or when bronchoscopy should be rapidly carried out, PB is technically more feasible. PMID- 1875749 TI - [Characterization of Haemophilus influenzae's resistance to ampicillin]. AB - BACKGROUND: The resistance of Haemophilus influenzae to ampicillin is nearly always dependent on plasmid-mediated betalactamase production. The betalactamase type most frequently identified was TEM-1; type ROB has occasionally been identified. The presence of plasmid-mediated betalactamase has been studied in H. influenzae strains moderately susceptible or resistant to ampicillin. METHODS: The test used in the detection of the presence of betalactamase was nitrocefin hydrolysis; the enzyme type was identified by analytic isoelectric focusing; the codifying gene of this betalactamase was identified by hybridisation with a TEM-1 probe labeled with digoxigenine. Strains studied were 110, obtained during the period 1987 to 1989 and isolated from four Hospitals of the Valles area of Barcelona. RESULTS: Enzyme production was detected in 105 of 110 strains studied; TEM-1 type betalactamase was identified in 108 and positive hybridisation was obtained in these strains with the TEM-1 probe. CONCLUSIONS: Nitrocefin hydrolysis is a reliable test for the detection of betalactamase production, although it may be unable to detect it (falses negatives) when the production is low. The only betalactamase type identified was TEM-1. The frequency of the strains with non-enzymatic resistance was 1.8%. PMID- 1875750 TI - [Treatment of solitary toxic thyroid nodule with 131I: results in 43 patients]. AB - BACKGROUND: Evaluation of the therapy with high-dose 131I in solitary toxic thyroid adenoma, with particular attention to the effects on thyroid function and on the nodular size. METHODS: A retrospective study of 43 patients with solitary thyroid nodule treated with radioactive iodine (mean dose 26.6 mCi, range 10-35) and followed up for 49.7 +/- 36.6 months (range 6-186) with periodical clinical, laboratory and echographic evaluations. RESULTS: Thirty-two patients (74.4%) had a normal thyroid function during follow-up. Five (11.6%) remained with hyperthyroidism and in 6 (13.9%) hypothyroidism developed 6-30 months after the administration of radioactive iodine. Three of these 6 had subclinical hypothyroidism, with mild increases in serum thyrotropin (TSH). Neither the development of hypothyroidism nor its persistence were significantly correlated with the initial thyroxin (T4) or triiodothyronine (T3) levels, the nodular size, the 131I dose, the incomplete inhibition of the extranodular thyroid parenchyma or the previous therapy with antithyroid drugs. The nodule diminished in size in 15 cases (38.4%), it disappeared in 9 (23%), it remained unchanged in 12 (30.7%) and it increased in 3 (7.7%). CONCLUSIONS: The treatment of the solitary toxic thyroid nodule with relatively high 131I doses is a safe and effective procedure, with a prevalence of residual hypothyroidism which is lower than previously reported. The disappearance of the nodule was only achieved in a minority of cases. PMID- 1875751 TI - [Non alcoholic steatohepatitis. Mid-term clinical and histologic course in 10 patients]. AB - BACKGROUND: The progressive character of the hepatic lesions in nonalcoholic steatohepatitis (NASH) has not been well established. In the present study, the clinical and histological course of this condition was evaluated at medium term. METHODS: Then patients (6 females and 4 males) with NASH, in a non-cirrhotic stage at the time of diagnosis, were followed up during 58 +/- 7 months (range 24 to 88 months). RESULTS: Nine patients were obese, but a significant reduction of body weight was found at the end of the study (p = 0.0072). Other clinical, physical or laboratory changes were not found, although in two cases hepatic biochemical tests were within normal limits when the follow-up biopsy was performed. Changes in the characteristic hepatic features were also absent, although fat infiltrates disappeared in three cases. Six patients had increased fibrosis and a progression of the hepatic architectural distortion; four reached the stage of cirrhosis. The evolution of the hepatic lesion correlated with the interval between diagnostic and follow-up biopsies (r = 0.69; p less than 0.05) and with the reduction in body weight (r = 0.64; p less than 0.05). CONCLUSIONS: In most cases, NASH results in a progressive hepatic distortion with can end in cirrhosis, although the change is slow and silent. PMID- 1875752 TI - [Value of bronchoalveolar lavage in the diagnosis of fungal and bacterial pneumonia]. PMID- 1875753 TI - [Pulmonary fibrosis]. PMID- 1875754 TI - [Septic thrombophlebitis of the great vessels of the neck. A severe complication of central venous catheters]. AB - Septic thrombophlebitis of the large veins of the neck is an uncommon, but extremely severe, complication in carriers of central venous catheters. Treatment of these cases is difficult and, generally, the clinical condition does not permit surgical approach. Four patients with septic central vein thrombophlebitis are reported. They were treated with conservative measures including catheter removal and high-dose parenteral antibiotics for at least four weeks, with excellent results in all. The relevant literature and the therapeutic alternatives are reviewed. PMID- 1875755 TI - [The patient with cancer and his or her family]. PMID- 1875756 TI - [Is endoscopic retrograde cholangiopancreatography essential for the diagnosis of cancer of the pancreas?]. PMID- 1875757 TI - [Health problems of the intercontinental traveler. Experience at the Clinic i Provincial Hospital of Barcelona]. PMID- 1875758 TI - [Tuberculosis mortality]. PMID- 1875759 TI - [Hemiballism and acquired immunodeficiency syndrome]. PMID- 1875760 TI - [Bronchial hyperreactivity in cough associated with angiotensin converting enzyme inhibitors]. PMID- 1875761 TI - [Pancreatic cancer and ABO blood types: a study of cases and controls]. AB - BACKGROUND: A hospital-based case-control study (controls were matched to cases by age, sex and hospital) has been carried out to analyze the relation between pancreatic cancer and blood type. METHODS: This study is based on data collected by the Boston Collaborative Drug Surveillance Programme. This large hospital based study has been collecting hospital admissions occurred in six different countries. To estimate relative risk (RR) associated with blood type, odds ratios were calculated by multiple logistic regression using conditional maximum likelihood estimation based on the matching factors (age, sex and hospital). The final analysis is based in 108 matched sets (108 cases and 374 controls). RESULTS: The results indicate a modest excess risk among persons with blood type A (RR = 1.52, 95% confidence interval: 0.87-2.67). Smoking was also a positive predictor of disease. CONCLUSIONS: In accordance with previous reports, this study shows some evidence of a positive association between blood type A and risk of pancreatic cancer. PMID- 1875762 TI - [Hospital morbidity statistics: the accuracy of the diagnosis reported in the discharge registry book]. AB - BACKGROUND: The registry book of admission and discharges (RBD) is operative in most public and private hospitals of this country. Currently its reformation is contemplated, consisting in a modification of the minimal set of basic data and its computerization. The aim of the present study was to evaluate the accuracy of the discharge diagnosis recorded in the RBD and to analyze the possible factors implicated in the current quality level. METHODS: In a sample of 9 hospitals from the Seville province, 2,634 discharges were selected with a stratified sampling process which was proportional to the number of discharges in each stratum during 1985. The accuracy of the diagnosis recorded in the RBD was estimated by comparing it with that in the clinical record (CR). RESULTS: The accuracy indexes showed that, for the large diagnostic groups, only in 45% of discharges the diagnosis coincided in both documents. The accuracy increased to 89% when the estimation was made after excluding those discharges where the diagnosis was not recorded in the RBD and/or in the CR (n = 1303). CONCLUSIONS: The fulfillment of the RBD appears as the main error source, followed by the selection of the major diagnosis and its transcription in the different documents of the circuit. It is concluded that a precondition for the success of a reformed RBD is to guarantee the fulfillment of data. PMID- 1875764 TI - [Can the occurrence of pancreatic cancer be prevented?]. PMID- 1875763 TI - [Deep venous thrombosis of the upper extremity: a study of 10 cases]. AB - BACKGROUND: Deep venous thrombosis (DVT) of upper limbs is less common than in lower limbs, although an increased prevalence has been observed in recent years. METHODS: The cases of DVT of upper limbs seen in an internal medicine service during a 24 month period were reviewed. Ten episodes out of overall 103 instances of DVT were identified (9.7%). The diagnosis was confirmed by colour echo-Doppler and/or phlebography. Subcutaneous calcium heparin was subcutaneously given at a dose of 2500 IU per 10 kg of body weight every 12 hours for 7 days, associated with oral anticoagulants given for a variable period in each case. RESULTS: The predisposing factors were: strenuous physical exercise (2 cases), oral contraceptives (2 cases), C-protein deficiency (1 case), parenteral drug abuse (PDA) (1 case), mediastinal mass (1 case), indwelling catheter (1 case) and absence of an apparent factor (2 cases). The colour echo-Doppler diagnosis was definitive in all cases where the study was carried out (8/10). The response to therapy was favourable in all cases. No case of pulmonary thromboembolism was found and post-phlebitic sequelae did not develop in the patients who could be followed up (6/10). CONCLUSIONS: The prevalence of deep venous thrombosis of upper limbs is increasing in recent years. The introduction of colour echo Doppler is a very helpful noninvasive diagnostic procedure. Subcutaneous calcium heparin at the reported dose is a good therapeutic approach. PMID- 1875765 TI - [How far to lower the arterial pressure of the hypertensive patient?]. PMID- 1875766 TI - [The hospital as an enterprise]. PMID- 1875767 TI - [Tuberous sclerosis]. PMID- 1875768 TI - [Multifocal hepatic steatosis simulating hepatic metastasis]. PMID- 1875769 TI - [Pleural effusion associated with lymphedema]. PMID- 1875770 TI - Computer-assisted series design in chemical synthesis of bioactive compounds. PMID- 1875771 TI - Evolution of the 4-anilidopiperidine class of opioid analgesics. PMID- 1875772 TI - Effects of sympathomimetic agents on opiate analgesia, tolerance and dependence in mice. AB - The effects of chronic pretreatment with ephedrine and phenylpropanolamine (PPA) on the antinociceptive activities of morphine and codeine, as well as their effects on the induction and expression of tolerance to, and dependence on morphine and codeine in mice are reported. Chronic pretreatment with ephedrine or PPA attenuated the antinociceptive effects of subsequently administered morphine or codeine. When administered during the induction phase, sympathomimetics enhanced opiate tolerance with little or no effect on the development of physical dependence. Given in the expression phase, ephedrine and PPA did not significantly affect tolerance, whereas there was significant suppression of withdrawal signs. The possible implications of these results are discussed. PMID- 1875773 TI - Interaction between the inhibitory effects of morphine and clonidine on intestinal transit in mice. AB - Both clonidine and morphine dose-dependently inhibited intestinal transit in mice. This inhibitory effect of clonidine was antagonized by prior administration of yohimbine but not by naloxone, while morphine's effect was antagonized by both yohimbine and naloxone. Morphine pretreatment did not induce any apparent tolerance to the effect of clonidine and morphine tested 4 h later. However, yohimbine became more potent in antagonizing the effect of clonidine while naloxone remained ineffective. Morphine pretreatment enhanced the antagonistic effectiveness of both yohimbine and naloxone against morphine. Clonidine pretreatment at a dose that did not induce any tolerance slightly enhanced the antagonistic effects of yohimbine and naloxone against morphine. Yohimbine also became more effective against clonidine but naloxone remained ineffective. At higher doses of clonidine pretreatment tolerance to the effects of morphine and clonidine were observed. These results suggest that both alpha 2-adrenoceptors and opioid receptors are involved in the inhibitory action of morphine on intestinal transit, while clonidine mainly acts through the alpha 2 adrenoceptors. In addition, there is a close interaction between the alpha 2 adrenoceptors and opioid receptors in the intestine. PMID- 1875774 TI - Lower environmental temperature: effect of long-term exposure on diazepam-induced changes in brain GABA. AB - Long-term diazepam (DZ) treatment (5 mg/kg, i.p. for 15-30 consecutive days) reduced GABAergic activity in hypothalamus and cerebellum with the alteration of GABA synthesis and its release process. This long-term DZ-induced inhibition in GABAergic activity in hypothalamus and cerebellum was not altered when DZ-treated rats were exposed (2 h/day) to lower environmental temperature (LET; 12 degrees C) for 7-30 consecutive days. Although repeated exposure to LET did not affect the GABA system in cerebellum and hypothalamus, striatal GABAergic activity was significantly enhanced under similar conditions. This LET-induced (repeated exposure) stimulation in striatal GABAergic activity was prevented when rats were treated with DZ along with repeated LET exposure (2 h/day) under long-term conditions. PMID- 1875775 TI - Changes in the adhesive phenotype of regional lymphocytes in rats with adjuvant arthritis: alteration by cyclophosphamide. AB - A quantitative spectrophotometrical method was used to study the adhesive phenotype of lymphocytes from regional lymph nodes of rats with early stage adjuvant-induced arthritis (AA), pretreated or not with cyclophosphamide (CY). The results showed that adhesion of lymphocytes from AA-sensitized lymph nodes to gelatin and collagens (type I, II, III and IV) was enhanced, especially to collagen type II. However, adhesion to fibronectin and to fibrinogen did not differ from adhesion in nontreated rats. Application of CY was found to aggravate AA development and influence the lymphocytes' adhesiveness. Adhesion was inhibited in all cases except to fibrinogen, where it was augmented, compared to the adhesion in both AA and control groups. Relationships between the lymphocyte adhesive phenotype and the expression of histological changes suggest that lymphocyte-matrix interactions could play an important role in the pathogenesis of AA development and the mechanism of CY action. PMID- 1875776 TI - The effect of some immunomodulators administration to rats on palmitic and oleic acids incorporation into the lipids of liver cell organelles. AB - The incorporation of equimolar doses of [14C]-palmitic and [3H]-oleic acids into the lipid moiety of hepatocytes after muramyl dipeptide (MDP), adamantylamide dipeptide (AdDP) and levamisole (LM) administration were investigated. The utilization of [14C]-palmitic acid for the synthesis of neutral lipids and phospholipids of crude nuclear fraction increased significantly after MDP and AdDP administration and to a lesser extent after LM. While the incorporation of [3H]-oleic acid did not change significantly after MDP and AdDP, LM significantly increased the incorporation of this acid into the phospholipids of nuclear and microsomal fractions. The changes in the incorporation of saturated palmitic and unsaturated oleic acids suggest a possible influence on deacylation-reacylation mechanisms. These changes could alter the physical properties of membrane and affect certain membrane functions, including the activity of membrane bound enzymes and transport mechanisms. PMID- 1875777 TI - Protein binding characterization of pethidine and norpethidine and lack of interethnic variability. AB - Using dialysis, incubation experiments and gas liquid chromatographic method, we studied the binding of pethidine (P) and norpethidine (N) to various protein components and plasma of both healthy volunteers and patients. The displacement interactions and interethnic variations of P and N were also examined. The (mean +/- S.D.) plasma protein binding ranged from 72 +/- 2.8 to 43 +/- 2.7% and from 57 +/- 3.0 to 27 +/- 3.9%, respectively, at various concentrations of P and N. Protein concentration-dependent binding was observed in P and N with albumin and alpha 1-acid glycoprotein. Albumin was found to be the major protein component in the binding, whereas gamma-globulin contributed smaller binding activity than other protein fractions at therapeutic concentration of the drugs. The binding affinities of P were comparatively higher than N in all circumstances. The % P bound was almost constant with respect to various concentrations of N and vice versa, indicating these two compounds exhibited no displacement action on the binding site to one another. The (mean +/- S.D.) % P bound for Caucasian, Chinese and Nepalese patients were 59 +/- 15%, 55 +/- 10% and 58 +/- 12%, respectively, at near 0.1 micrograms/ml of P, implying the absence of interethnic variation in P protein binding. PMID- 1875778 TI - Nephrotoxicity of tobramycin. Value of examining various protein and enzyme markers. AB - The value of various protein and enzyme markers for the assessment of early nephrotoxicity of tobramycin was studied in 18 patients with febrile infection. The renal clearance of creatinine and the excretion of the following protein and enzyme markers were measured on the first and the last day of the 5-8 day treatment period: albumin, N-acetyl-beta-D-glucosaminidase (NAG), beta 2 microglobulin, alpha-amylase, lysozyme and retinol-binding protein (RBP). Diurnal excretions of beta 2-microglobulin, lysozyme and RBP, all markers of tubular dysfunction, were already increased on the first treatment day, compared to similar control patients treated with non-aminoglycoside antibiotics and reference values of our laboratory. The excretion of NAG, an enzyme released from tubular cell lysosomes, was not increased initially, but on the last treatment day it was increased most consistently of all the markers studied. Glomerular filtration rate was halved in 5 of the patients. The results suggest that the initial increase in beta 2-microglobulin, lysozyme and RBP excretion is a result of an early tubular transfer block by tobramycin, whereas the late increase in NAG excretion probably reflects the progress of tubular cell damage during the course of aminoglycoside therapy. PMID- 1875779 TI - Coronary atherosclerosis: current therapeutic approaches and future trends. AB - Invasive cardiovascular procedures, such as percutaneous translumenal coronary angioplasty (PTCA) and aorto-coronary bypass surgery (ACBS), that are currently employed in treating the coronary stenosis or occlusion caused by atherosclerosis represent a major therapeutic advance for managing coronary heart disease (CHD). However, the cellular proliferative response and associated intimal hyperplasia that can follow the damage to blood vessels that occurs with these procedures leads to late complications which cannot be effectively controlled by presently available drugs. Hence, a new approach is required for managing these complications, termed "restenosis" (in the case of PTCA) or "stenosis" (in the case of ACBS). Existing drug therapy is reviewed and some new approaches to this problem are provided herein. Further studies of growth factors and other substances that influence the cellular proliferative response that follows injury to the blood vessel wall could lead to the development of effective therapy. Inhibition of intimal hyperplasia and/or acceleration of endothelial cell re growth provide a basis for such new approaches. Platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), as well as endothelium-derived relaxing factor(s) (EDRF) and calcitonin gene-related peptide (CGRP) are among the substances discussed. Modification of certain currently available drugs (e.g. Ca(2+)-antagonists) could also be of value in meeting this therapeutic demand. PMID- 1875780 TI - Evidence that nitric oxide modulates food intake in mice. AB - Nitric oxide (NO) may be an intercellular modulator within the central nervous system. L-arginine, which results in NO synthesis, increased food intake in mice while the inhibitor of NO synthesis, L-NG-nitro arginine (L-NO Arg) inhibited food intake in food deprived mice. L-arginine, but not D-arginine, partially reversed the inhibitory effect of L-NO Arg on food intake. These findings suggest the possibility that NO may be a physiological modulator of food intake and that the possibility of exploring the utility of L-NO arg in the treatment of obesity should be explored. PMID- 1875781 TI - Catechol-O-methyltransferase and aromatic L-amino acid decarboxylase activities in human gastrointestinal tissues. AB - Human gastrointestinal samples from the corpus, antrum, bulbus, jejunum and ileum were assayed for soluble and membrane-bound catechol-O-methyltransferase (COMT) and aromatic L-amino acid decarboxylase (AADC) activity in vitro. The mean soluble COMT activities with 3,4-dihydroxybenzoic acid (DBA) and 3,4 dihydroxyphenylalanine (L-DOPA) as substrate were 70-242 and 70-174 pmol/min mg, respectively. The membrane-bound COMT activities ranged from 33 to 60 pmol/min mg in the different parts of the intestine. The AADC activities, measured with L DOPA as the substrate, increased from 114 pmol/min mg in the corpus to 3488 pmol/min mg in the jejunum. The affinity of the soluble COMT was approximately 20 times higher for DBA (Km 15-19 microM) than for L-DOPA (Km 300-600 microM). The Km-values for L-DOPA of AADC and COMT were of the same order of magnitude. The specific COMT inhibitors, nitecapone and OR-611, effectively inhibited in vitro the human intestinal COMT activity. Nanomolar concentrations caused 50% inhibition with both DBA and L-DOPA as substrate. PMID- 1875782 TI - Antagonism of the morphine-induced locomotor activation of mice by fructose: comparison with other opiates and sugars, and sugar effects on brain morphine. AB - The mouse locomotor activation test of opiate action in a 2+2 dose parallel line assay was used in a repeated testing paradigm to determine the test, opiate and hexose specificities of a previously reported antagonism of morphine-induced antinocociception by hyperglycemia. In opiate specificity studies, fructose (5 g/kg, i.p.) significantly reduced the potency ratio for morphine and methadone, but not for levorphanol, meperidine or phenazocine when intragroup comparisons were made. In intergroup comparisons, fructose significantly reduced the potencies of levorphanol and phenazocine, but not methadone or meperidine. In hexose/polyol specificity studies, tagatose and fructose significantly reduced the potency ratio for morphine, whereas glucose, galactose, mannose and the polyols, sorbitol and xylitol, caused no significant decrease in potency. Fructose, tagatose, glucose and mannose (5 g/kg, i.p.) were tested for effects on brain morphine levels 30 min after morphine (60 min after sugar), and all four sugars significantly increased brain morphine relative to saline-pretreated controls. It is concluded that the antagonism of morphine by acute sugar administration shows specificity for certain sugars and occurs despite sugar induced increases in the distribution of morphine to the brain. Furthermore, the effects of fructose show an opiate specificity similar to that of glucose on antinociception observed previously in our laboratory, except that methadone was also significantly inhibited in the present study, when a repeated-testing experimental design was used. PMID- 1875783 TI - Effect of photoperiod on body weight and food intake of obese and lean Zucker rats. AB - Although the rat is usually not considered to be sensitive to photoperiod, under some experimental conditions photoperiod responses are unmasked. In addition, we have observed photoperiod-induced changes in body weight gain in lean and obese Zucker rats. In this experiment, body mass, food intake, body composition, brown adipose tissue (BAT) thermogenic state, and blood concentrations of corticosterone, insulin, and glucose were evaluated under one of two lighting conditions: a short (10 h light: 14 h dark) or a long (14 h light: 10 h dark) photoperiod. Plasma corticosterone and glucose concentrations measured under fasting conditions were unaffected by photoperiod in either genotype. The amount of BAT mitochondrial protein isolated was less in long photoperiod rats. BAT mitochondrial GDP binding was unaffected by photoperiod in the lean rats, but tended to be lower in long photoperiod obese rats than in short photoperiod obese rats. Although, photoperiod had no effect on daily food intake of rats exposed to the short versus long photoperiod, body mass was heaviest in obese rats raised in long photoperiod. Plasma insulin was increased in both lean and obese rats in long photoperiod. In addition, fat storage appeared to shift to internal depots in the lean rats exposed to long photoperiod. Our data demonstrate that photoperiod does have an effect on male Zucker rats with respect to body weight and fat distribution, with the obese rats being more sensitive to changes in photoperiod than the lean rats. PMID- 1875784 TI - Vasorelaxant effect of C16-PAF and C18-PAF on renal blood flow and systemic blood pressure in the anesthetized rat. AB - The renal vasoactive and systemic hypotensive effects of platelet activating factor (C16:0-PAF and C18:1-PAF) were examined in anesthetized male Wistar rats. Bolus injections of C16-PAF (0.5-25 ng/kg) and C18-PAF (2.5-200 ng/kg) into the arterial circulation of the kidney produced increases in renal blood flow (6-15%) before causing dose-dependent systemic hypotension (2-64 mmHg). The dose-response curves for renal blood flow and systemic blood pressure generated by intrarenal C18-PAF administration were approximately 7 fold to the right of the dose response curves generated by C16-DPAF. Intrarenal injections of vehicle or the biologically inactive enantiomer C16-DPAF (25-200 ng/kg) did not affect renal blood flow or systemic blood pressure. These results suggest that C16:0-PAF is a more potent renal vasodilator and hypotensive lipid than C18:1-PAF. PMID- 1875785 TI - Reduced levels of mRNA for myofibrillar proteins in skeletal muscle from septic rats. AB - The influence of sepsis on transcription of myofibrillar proteins in skeletal muscle was studied in rats. Sepsis was induced by cecal ligation and puncture (CLP); control rats were sham-operated. Sixteen hours later, muscle levels of mRNA for myofibrillar proteins were determined by using cDNA probes specific for transcripts for alpha actin and myosin heavy chain. Sepsis resulted in a 2-6 fold decrease in alpha actin mRNA levels and an even more pronounced reduction in myosin heavy chain mRNA levels. Results suggest that sepsis-induced reduction of muscle protein synthesis is at least partly regulated at the transcriptional level. PMID- 1875786 TI - Regulation of 35S-TBPS binding by bicuculline is region specific in rat brain. AB - The allosteric regulation of specific 35S-TBPS binding to the convulsant site on the GABAA receptor/chloride (Cl-) ionophore complex was studied in various brain regions in an attempt to characterize regional heterogeneity of the protein subunits forming the complex. Bicuculline methiodide (BIC), a GABAA antagonist, enhanced binding in cortex (CTX), substantia nigra (SN) and cerebellum (CBL), inhibited binding in inferior colliculus (IC) and did not affect binding in superior colliculus (SC). Similar results were found in CBL and IC using SR 95531, another GABAA antagonist. The levels of endogenous GABA in the different tissue samples could not account for the regional differences in binding. When the functional regulation of these receptors was measured using 36Cl- uptake in microsomes, muscimol-stimulated uptake was completely blocked by BIC in CBL and IC but was not affected by BIC in SC. Additionally, picrotoxin completely blocked muscimol-stimulated uptake in CBL but had no effect in IC or SC. These findings provide a functional basis for regional heterogeneity of GABAA receptor. PMID- 1875787 TI - Endothelin-1-induced nociception. AB - Intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of morphine to mice antagonized the abdominal constriction induced by an i.p. injection of endothelin-1 (ET-1; 0.1 mg/kg). The ED50 values (95% confidence intervals) were 39.3 (16.5-80.2) ng and 1.5 (0.8-4.9) ng, respectively. The antagonism of ET-1 induced abdominal constriction by morphine was blocked by naloxone (1.0 mg/kg, s.c.) or by 24 h pretreatment with beta-funaltrexamine (beta-FNA; 8.84 micrograms, i.c.v.). These results demonstrate for the first time that the stimulus resulting from an i.p. injection of ET-1 is transmitted via ascending (pain) pathways that are subject to attenuation by opioid (mu) receptor activation. Hence, ET-1-induced abdominal constriction is a new pain model which, given the other pharmacology of ET-1, might represent a unique model with potential specific utility for anginal or other visceral pain. PMID- 1875788 TI - The treatment of late luteal phase dysphoric disorder. AB - This mini-review provides a comprehensive discussion of the management of the late luteal phase dysphoric disorder (LLPDD). The various treatments will be described with particular attention to their efficacy and the nature of side effects. These include: psychoactive drugs (lithium, anxiolytics, antidepressants), nutritional agents (L-tryptophan, Vitamin B6, prostaglandins precursors and inhibitors), dopamine agonists, diuretics, antihypertensives, hormonal interventions (gonadotrophin releasing hormone analogues, oestradiol, tamoxifen, progesterone, danazol, and oral contraceptives). Less attention has been given to non-pharmacologic approaches such as diet, exercise and psychotherapy. The availability of an operational definition of LLPDD in the DSM III-R and the improvement in research methodology has provided a clearer direction for clinical management and for future investigations. PMID- 1875789 TI - Stimulation of pulmonary surfactant secretion by activating neutrophils in rat type II pneumocytes culture. AB - The influence of activating neutrophils on the secretion of phosphatidylcholine (PC), the predominant component of pulmonary surfactant, was examined using primary culture of rat type II pneumocytes. Simultaneous addition of neutrophils and opsonized zymosan, but not neutrophils or opsonized zymosan alone, to type II pneumocytes caused a significant increase in PC secretion without affecting the release of lactate dehydrogenase, a marker of cytotoxicity. The increase in PC secretion was dependent on the number of activating neutrophils. In addition, pretreatment of culture with the combination of superoxide dismutase and catalase inhibited the increase in PC secretion. These findings indicate that activating neutrophils stimulate the secretion of pulmonary surfactant and that the stimulation is mediated by oxygen radicals. PMID- 1875790 TI - Effect of nasal instillation of female urine or vaginal exudate on serum cortisol and prolactin levels in isolated and anesthetized male rhesus monkeys (Macaca mulatta). AB - Two male adult rhesus monkeys were used and caged individually. The room was temperature-controlled having a light-dark period of 12/12 hours. The animals were rapidly immobilized and immediately anesthetized with ketamine i. m. (10 mg/kg of body weight). They were bled four times at 15, 30, 45 and 60 mins after the ketamine injection, twice a week for 6 weeks. When necessary, maintenance doses of ketamine were administered. The serum levels of cortisol and prolactin after nasal instillation of a suspension of vaginal exudate showed lower values than in control conditions (nasal instillation of saline). The control levels of cortisol tended to increase up to 60 mins, whilst in experimental conditions (nasal instillation of female urine or vaginal exudate) did not show such an increase. Cortisol remained similar during the sampling and similar to the 15 mins control levels, but the difference is statistically significant only after instillation of vaginal exudate as compared with control. The levels of prolactin did not show significant variations during sampling either in control or after female urine instillation. However, the instillation of vaginal exudate decreased the prolactin levels at 15 mins which tended to recover the control levels up to 60 mins. These results support the hypothesis, discussed in a previous paper, that some chemical information from females suppresses or mitigates the effect of acute stress resulting from handling the animals before anesthesia. PMID- 1875791 TI - Fluoxetine pretreatment reduces breaking points on a progressive ratio schedule reinforced by intravenous cocaine self-administration in the rat. AB - Fluoxetine, a specific serotonin re-uptake inhibitor, reduced the breaking points reached by rats on a progressive ratio (PR) schedule reinforced by intravenous cocaine (0.6 mg/inj). This effect was dose-dependent. Specifically, fluoxetine (2.5, 5.0, 10.0, and 20.0 mg/kg, IP) significantly decreased breaking points at all but the lowest dose. These data support a role for the serotonergic system in cocaine reinforcement. We argue that facilitating serotonergic activity reduces the rewarding value of cocaine, thus suggesting an aversive role for serotonin in cocaine reinforcement. PMID- 1875792 TI - Phosphoramidon prevents cerebral vasospasm following subarachnoid hemorrhage in dogs: the relationship to endothelin-1 levels in the cerebrospinal fluid. AB - There is increasing evidence that the conversion of big endothelin-1 (big ET-1) to endothelin-1 (ET-1) is specifically inhibited by the metalloproteinase inhibitor phosphoramidon. We investigated the effect of phosphoramidon on delayed cerebral vasospasm from subarachnoid hemorrhage (SAH) using a two-hemorrhage canine model. The magnitude of the vasospasm and the drug effect were determined angiographically. On SAH Day 7, diameter of the basilar artery decreased to about 55% of the control value obtained before SAH (on Day 0). Immunoreactive ET (IR ET) in the cerebrospinal fluid (CSF) significantly increased after SAH (on Day 7). The intracisternal pretreatment of phosphoramidon potently suppressed the decrease in diameter of the basilar artery after SAH, i.e., observed decrease was only about 20%, compared with the value before SAH. In the phosphoramidon group, IR-ET in CSF markedly increased (on SAH Day 2), but the increased levels of IR-ET significantly declined on SAH Day 7. These results clearly indicate that phosphoramidon effectively prevents delayed cerebral vasospasm. Whether the prevention is due to the inhibition of conversion of big ET-1 to ET-1 is now under study. PMID- 1875793 TI - Gossypol effects on endothelial cells and tumor blood flow. AB - Isomers (-, +) of the antitumor agent gossypol (G) were studied for their ability to reduce tumor ATP and blood flow in rats bearing subcutaneously implanted pancreatic tumors. A 50% reduction in tumor ATP/Pi within ih of a single injection of -G was associated with a 60% decline in tumor blood flow. To determine if these changes in tumor physiology could be due to a direct drug effect on tumor endothelium, G isomers were compared for their ability to alter protein (125I-BSA) permeability and metabolic (32P) labelling of cultured endothelial cells. Treatments for ih produced no endothelial cell leakage, but 24h exposures to either -G (5 microM) or +G (50 microM) produced complete permeability of the monolayers to 125I-BSA. In contrast, 0.5-I.Oh exposures to -G (4 microM) produced 2 to 3-fold increases in phosphorylated 27 kDa heat-shock protein, hsp-27. Hsp-27 phosphoprotein isoforms were differentially labelled following -G and +G exposures with the phosphorylation profile of -G appearing most similar to that of oxyradical producing agents known to induce hsp-27 and injure endothelial cells. We postulate that the tumor ischemic effects of -G are mediated by endothelial response to oxyradical production in a mechanism similar to that of tissue ischemia-reperfusion injury. PMID- 1875795 TI - Enhanced enzyme-linked immunosorbant assay on membranes for the identification of mutants and pathogens. AB - With variations in the concentrations of antibodies and blocking agents and reduction in incubation times, qualitative enzyme-linked immunosorbant assay can be performed in a matter of two hours, for more rapid identification of mutants and antigens. PMID- 1875794 TI - Amelioration of hyperlipidemia by low fat diets in chronically streptozotocin diabetic rats. AB - The effects of reduced dietary fat intake on plasma lipid levels were examined in diabetic rats. One week after induction of diabetes (D) with streptozotocin (65 mg/kg, iv), the animals were fed food pellets consisting of 1.5% (D1.5), 2.5% (D2.5) or 5% (D5) fat for two weeks. Irrespective of the diets, both food and water consumed by untreated diabetic rats were 2- to 5-fold greater respectively compared to normal. Plasma glucose concentrations were also similarly increased. Plasma and skeletal muscle lipid levels were significantly greater than controls in D2.5 and D5, but not in the D1.5 group. Plasma and muscle lipid concentrations correlated directly with fat consumption. In D5 rats receiving insulin treatment, plasma glucose and lipid concentrations were comparable to control values. These findings indicate that the degree of hyperlipidemia in chronically diabetic rats is directly related to dietary fat intake. They also demonstrate that dietary interventions can modulate some of the metabolic abnormalities in diabetes. PMID- 1875796 TI - Prostaglandin synthesis is increased in selenium supplemented human mesangial cells despite suppression of phospholipase A2-activity. AB - Antioxidants play an important role in the regulation of phospholipid hydrolysis and arachidonate metabolism. Supplementation of cultured human mesangial cells with selenium resulted in suppression of phospholipase A2-activity and significantly increased production of three major prostaglandins. However, prostacyclin synthesis benefits most from selenium supplementation, suggesting that there is a specific action of selenium-dependent glutathione peroxidase on this pathway. Like in endothelial cells, production of platelet activating factor is significantly inhibited by selenium supplementation. PMID- 1875797 TI - Aminoguanidine decreases urinary albumin and high-molecular-weight proteins in diabetic rats. AB - The effect of aminoguanidine (AG) on diabetic proteinuria was studied in control rats ([C]), streptozotocin (SZ)-induced diabetic rats ([DM]), control rats treated with AG [( C + AG]), or diabetic rats treated with AG [( DM + AG]). Increased glycation of hemoglobin (HbA1C), and glomerular basement membrane (GBM) type IV collagen (IV-C) at 10 wk of stable diabetes were associated with the appearance of high-molecular-weight (HMW) cross-linked type I collagen and HMW proteinuria of 62 kD, 69 kD albumin and 77 kD proteins to the levels of 362, 381, and 408%, while 9.9, 13.5, 17, 18, and 23 kD proteins were decreased, respectively, to non-detectable, 37, 16, and 13%. AG decreased cross-linkage of type I collagen and significantly decreased urinary 62 kD protein to 54%, 69 kD albumin to 40%, and 77 kD protein to 49% at 10 wk in [DM + AG] compared to [DM] without changing diabetic control. It is suggested that glycation-derived late stage protein modification is etiologically important for diabetic proteinuria, and that AG can potentially prevent diabetic HMW proteinuria. PMID- 1875798 TI - Upregulation of glucose metabolism by granulocyte-monocyte colony-stimulating factor. AB - Alterations of glucose metabolism were investigated for 6 hours following an intraarterial injection of murine recombinant granulocyte-monocyte colony stimulating factor (GM-CSF) (30 micrograms/kg body weight). GM-CSF resulted in a transient elevation of plasma glucose. The rate of whole body glucose appearance, as measured by infusion of [6-3H] glucose, was increased by about 10% between 0.5 and 3 hours following GM-CSF injection. In vivo glucose utilization of individual tissues was investigated by the tracer 2-deoxyglucose technique. At 30 min, GM CSF increased glucose utilization by 80-90% in liver and lung, and 50-60% in skin and spleen. At 3 and 6 hours, glucose utilization by these tissues returned toward control levels except for lung. There was a 40-50% increase in glucose utilization by skeletal muscle 30 min after GM-CSF which was sustained for 6 hours. Glucose utilization of testis, ileum and kidney did not change significantly. Plasma concentrations of insulin, glucagon and tumor necrosis factor were not altered in response to GM-CSF. These findings indicate that some of the acute metabolic effects of a short-term administration of GM-CSF are observed in macrophage-rich tissues, and suggest that GM-CSF may be involved in the metabolic upregulation of immunologically active tissues. PMID- 1875799 TI - Sensitization does not alter phasic and tonic responses to carbachol in isolated epithelium-free guinea-pig trachea. AB - An alteration in the handling of Ca2+ has been proposed as the pathogenic mechanism underlying the airway smooth muscle hyperresponsiveness of asthma. The present study tested the hypothesis that the altered responsiveness of receptor operated contraction to carbachol in allergic asthma results from a change in the phasic or tonic components. Using a kinetic approach, the phasic and tonic responses to 10 microM carbachol were quantitated in isolated epithelium-free trachea 21 days after guinea-pigs were sensitized with ovalbumin and aluminum hydroxide (as adjuvant) to generate preferentially IgE-like antibodies. Sensitization was confirmed by challenge of the isolated trachea with ovalbumin. The steady-state and kinetic characteristics of the phasic and tonic responses were the same from sensitized animals and animals treated with saline and aluminum hydroxide (control) and before and after challenge of the trachea from both groups of animals. The present results demonstrate that immunologic sensitization and challenge do not appear to elicit a defect in the phasic or tonic responses of receptor mediated contractions in airway smooth muscle and suggest there is no alteration in the handling of Ca2+ in smooth muscle from sensitized and challenged guinea-pig trachea. PMID- 1875800 TI - Inhibition of hepatic adenylate cyclase by NADH. AB - Adenylate cyclase activity in isolated rat liver plasma membranes was inhibited by NADH in a concentration-dependent manner. Half-maximal inhibition of adenylate cyclase was observed at 120 microM concentration of NADH. The effect of NADH was specific since adenylate cyclase activity was not altered by NAD+, NADP+, NADPH, and nicotinic acid. The ability of NADH to inhibit adenylate cyclase was not altered when the enzyme was stimulated by activating the cyclase was not altered when the enzyme was stimulated by activating the Gs regulatory element with either glucagon or cholera toxin. Similarly, inhibition of Gi function by pertussis toxin treatment of membranes did not attenuate the ability of NADH to inhibit adenylate cyclase activity. Inhibition of adenylate cyclase activity to the same extent in the presence and absence of the Gpp (NH) p suggested that NADH directly affects the catalytic subunit. This notion was confirmed by the finding that NADH also inhibited solubilized adenylate cyclase in the absence of Gpp (NH)p. Kinetic analysis of the NADH-mediated inhibition suggested that NADH competes with ATP to inhibit adenylate cyclase; in the presence of NADH (1 mM) the Km for ATP was increased from 0.24 +/- 0.02 mM to 0.44 +/- 0.08 mM with no change in Vmax. This observation and the inability of high NADH concentrations to completely inhibit the enzyme suggest that NADH interacts at a site(s) on the enzyme to increase the Km for ATP by 2-fold and this inhibitory effect is overcome at high ATP concentrations. PMID- 1875801 TI - The importance of volume in regulating gastric emptying. AB - There is now substantive evidence that the provision of exogenous carbohydrate at high rates (1-2 g. min-1) can enhance performance during prolonged exercise. This finding has revived research into the factors determining the rate of exogenous carbohydrate delivery during exercise. While the rate of muscle oxidation of exogenous carbohydrate could be determined by the rate of gastric emptying or of intestinal carbohydrate absorption or of muscle glucose uptake and oxidation, most physiologists seem to have assumed that gastric emptying is the factor that limits the rate of exogenous carbohydrate delivery during exercise. Furthermore, studies of gastric emptying have suggested that the carbohydrate content of the ingested solution is an important factor determining its rate of gastric emptying. However, the findings of recent studies employing a repeated drinking design suggest that the gastric volume and therefore the pattern of drinking during exercise will have a significant, possibly major, influence on the rate of both carbohydrate and water delivery from any solution. This review considers this evidence and its practical implications for athletes who wish to ingest carbohydrate during exercise and for exercise physiologists designing studies to optimize carbohydrate delivery to muscle during exercise. It is proposed that, if gastric volume is an important determinant of the rate of gastric emptying, a more standardized method for reporting the rates of gastric emptying of different solutions should be adopted. PMID- 1875802 TI - Why haven't we learnt our lesson? Autologous blood transfusion. PMID- 1875803 TI - The special hostel for care of people with dementia. PMID- 1875804 TI - A positive AIDS test--how to tell? PMID- 1875805 TI - Of ends and means. PMID- 1875806 TI - The Western Australian Centre for Remote and Rural Medicine. PMID- 1875807 TI - Elderly patients' responses to preoperative autologous blood collection. AB - OBJECTIVE: To follow the haematological response in elderly patients to preoperative autologous blood collection. DESIGN: A prospective, randomised study. SETTING: Malmo General Hospital, Sweden. PATIENTS: Sixty patients with a mean age of 71 years (range, 60-82 years) who were to undergo total hip replacement were randomly divided into four groups of 15. One group served as control. Three units of blood were collected from patients in the other three groups, the first unit at least 30 days before the planned operation, with an average interval of 10 days between collections. Iron supplementation was given to one group as a substitution remedy, another group was given iron and folic acid and the third group was without supplementation during the collection period. MAIN OUTCOME MEASURES: Haematological and biochemical tests were performed on blood samples taken at the time of each collection, on the morning of the hip replacement operation, and ten days after and six weeks after the operation. RESULTS: No major complication was encountered with blood collection. The patients tolerated the procedure very well including the substitution remedies. Haematological and biochemical parameters remained within the normal range during the collection period and after the operation. No patient in the autologous groups needed homologous blood during the operation; three units of homologous blood were used after the operation in these patients. CONCLUSION: Preoperative blood collection from the elderly is safe and well tolerated. The procedure should be encouraged in elective orthopaedic operations regardless of age. PMID- 1875808 TI - Continuing medical education undertaken by general practitioners using the rural registrar scheme. AB - OBJECTIVE: To evaluate the first full year of operation of the rural registrar scheme by comparing the educational activities undertaken by the participating rural general practitioners with those undertaken in the previous year. DESIGN: Retrospective questionnaire survey mailed to all participants. SETTING: Continuing medical education (CME) for rural general practitioners (GPs) in South Australia. PARTICIPANTS: All 25 GPs who used the scheme from July 1989 to June 1990 were included in the study. All were from solo or two person practices in rural South Australia. One had gone abroad and could not be contacted, and 23 of the remaining 24 responded. INTERVENTIONS: A competent locum was supplied at no cost to the GP, so that the GP could leave the practice to undertake CME. MAIN OUTCOME MEASURES: GPs were asked to outline CME activities for two consecutive years, to rate the educational value of each activity, and to note whether skill or knowledge acquisition was most relevant. RESULTS: The rural registrar scheme increased the amount of time that rural GPs spent on CME. The range of topics studied increased considerably. CONCLUSIONS: The provision of a satisfactory locum service has enabled rural GPs to participate in a wide range of CME activities, which reflect the diversity of general practice. Most participants preferred individual, experiential study programmes to more structured CME programmes. PMID- 1875809 TI - Bacterial meningitis in children under five years of age in Western Australia. AB - OBJECTIVES: To describe the epidemiology and the associated mortality and serious neurological sequelae of bacterial meningitis in children under five years of age in Western Australia, and to consider the potential impact of a Haemophilus influenzae type b vaccine on this group of children. DESIGN: A retrospective survey, using multiple sources of case ascertainment. PATIENTS: All children in Western Australia from one month to five years of age who developed bacterial meningitis, over a five-year period (from 1984 to 1988 inclusive). MAIN OUTCOME MEASURES: Episodes of bacterial meningitis, deaths associated with bacterial meningitis, and sensorineural deafness (requiring hearing aids) and cerebral palsy following bacterial meningitis. RESULTS: Two hundred and seventy episodes of bacterial meningitis were identified; 200 occurred in non-Aboriginal children and 70 in Aboriginal children. There were 16 meningitis-associated deaths (case fatality rate, 5.9%), 7 children developed profound sensorineural deafness and a further 7 children developed cerebral palsy after bacterial meningitis. H. influenzae type b caused nearly 70% of the cases of childhood bacterial meningitis. The annual incidence rate of H. influenzae meningitis was significantly greater in Aboriginal children (150 episodes per 100,000 children under five years of age per year) than in non-Aboriginal children (27 episodes per 100,000), and the mean age of onset of H. influenzae meningitis was significantly lower in Aboriginal children (6.8 months) than in non-Aboriginal children (19.8 months). CONCLUSIONS: Any conjugate H. influenzae type b vaccine should be effective when administered to non-Aboriginal children in the first six months of life, but only the most immunogenic vaccines (for example, the vaccine known as PRP-OMP) are likely to be effective in Aboriginal infants. PMID- 1875810 TI - Investigating male sexual dysfunction. Cavernosograms and penile flow studies. PMID- 1875811 TI - Principles behind practice. 7. Case-control studies. AB - The case-control study is often a very simple, cheap and quick way to test the hypothesis that a particular factor causes a disease or that a particular treatment is helping patients who receive it. There also seems to be an inherent logic in comparing patients and well people to see how they differed in the past, or in comparing those who did and did not survive a certain illness to see how their treatment differed. Despite these appealing features, the case-control approach is subject to a number of pitfalls. These can usually be avoided by an appropriately designed study, and by careful collection and analysis of the data. Even so, the results of a case-control study are a lower order of evidence than those produced from a properly conducted randomised controlled trial. PMID- 1875813 TI - "Doctor, I don't feel sick, but ...": the older patient. PMID- 1875812 TI - Seeing red. Flushed orbit and red eye. PMID- 1875815 TI - The physician as a patient. PMID- 1875814 TI - Reactions to argasid tick bites by island residents on the Great Barrier Reef. AB - OBJECTIVE: To attribute a cause and quantify allergic-like symptoms observed among island residents. DESIGN: Skin prick tests and intradermal injections with ultraviolet-irradiated, filtered (0.22 microns) whole-body homogenates of the soft tick, Ornithodoros capensis, were used to reproduce experimentally the symptoms observed. SETTING: Heron Island, Great Barrier Reef, Australia. PARTICIPANTS: Island residents were designated as such after having spent more than 1 month on the island during the summer seabird breeding season. INTERVENTIONS: Control measures were instigated using a residual insecticide, delta-methrin, sprayed inside sleeping quarters. MAIN OUTCOME MEASURES: Acaricide spraying reduced (X2 = 4.42; P less than 0.05) the number of island residents complaining of having been bitten by ticks, yet was considered an inefficient control measure as 67% reported being attacked by ticks after spraying. RESULTS: Among 97 island residents, elevated total IgE levels were associated with reaction to tick bite in 11 cases (X2 = 27.17; P less than 0.001), but were not of reliable diagnostic value. Symptoms included intense pruritus, blistering (a major feature), erythema, weeping lesions, lymphangitis, dull ache, rheumatic pain and general lassitude, and intense discomfort. Sera from two of four volunteers with known reactions to O. capensis and one of four others with reactions to the Australian paralysis tick, Ixodes holocyclus, cross-reacted with antigens from a total of four of six biting/stinging and non-biting arthropods (radioallergosorbent tests). CONCLUSIONS: Symptoms associated with reactions to tick bite peaked in severity at 35-40 hours and thus the response was most likely delayed type IV hypersensitivity. PMID- 1875816 TI - Isospora belli infection. A report of two cases in patients with AIDS. AB - OBJECTIVE: To present the findings of Isospora belli infection in two patients with the acquired immunodeficiency syndrome (AIDS). CLINICAL FEATURES: One patient was part Aboriginal, the other an immigrant recently arrived from Peru. Both men were infected with the human immunodeficiency virus (HIV). They presented with watery diarrhoea, one with severe weight loss. Isospora belli oocysts were detected in multiple faecal specimens from both patients. One patient had a concomitant infection with Cryptosporidium sp. INTERVENTION AND OUTCOME: There was a rapid response to treatment with cotrimoxazole (960 mg, four times a day for 10 days). A complete response was obtained in the patient with concurrent cryptosporidiosis. The diarrhoea recurred after cessation of treatment, necessitating maintenance therapy. CONCLUSION: Although Isospora belli is an uncommon cause of gastroenteritis in Australia, it is increasingly recognised as a cause of diarrhoea in travellers, immigrants from endemic areas and immunocompromised people. It has also been reported in the Aboriginal community; this article reports the first case of AIDS-related isosporiasis in an Aborigine. It is likely that both patients acquired Isospora belli before they become HIV seropositive. PMID- 1875817 TI - Hospital admissions due to drug reactions. PMID- 1875818 TI - Let ethics committees authorise new drugs for treatment. PMID- 1875819 TI - Cervicothoracic pain due to fatigue of pectoral girdle musculature. PMID- 1875820 TI - Sabin oral poliomyelitis vaccine. PMID- 1875821 TI - Thiamine in our bread and wine. PMID- 1875822 TI - Acupuncture for bronchial asthma? PMID- 1875823 TI - EMLA Cream and herpetic neuralgia. PMID- 1875824 TI - Gentian violet. PMID- 1875825 TI - More "cot death" fallacies. PMID- 1875826 TI - Potential health effects of greenhouse effect and ozone layer depletion in Australia. PMID- 1875827 TI - Australian patterns of tobacco smoking in 1989. PMID- 1875828 TI - Necrotising arachnidism in Australia. PMID- 1875829 TI - Insulin therapy: how many injections? PMID- 1875830 TI - Opposition from deaf groups to the cochlear implant. PMID- 1875831 TI - Medicines in pregnancy. PMID- 1875832 TI - Airbags: safety delayed. PMID- 1875833 TI - Frequent hospital admissions for bacterial infections among aboriginal people with diabetes in central Australia. AB - OBJECTIVE: To determine hospital-based morbidity and mortality from bacterial infections among Aboriginal people with diabetes in central Australia. DESIGN: Examination of medical records on diabetic inpatients between January 1984 and December 1986. SETTING: Alice Springs Hospital in central Australia, covering an Aboriginal population of about 12,500 people. PATIENTS: Subjects admitted with a bacterial infection (n = 165) were selected from the database of all Aboriginal people known to have diabetes in the region (n = 374; all had non-insulin dependent diabetes). MAIN OUTCOME MEASURES: Number of admissions, type and site of infections, causative organisms, duration of hospital stay and cause of death. RESULTS: The 281 admissions for infections accounted for 4.6% of adult Aboriginal admissions to hospital. Thirteen patients died. Eleven patients required amputation of a digit or limb. In 1986, 13/200 patients admitted with diabetes had bacteraemia compared with 14/1885 patients who did not have diabetes. One patient had Fournier's gangrene, one had malignant otitis externa, one community acquired Acinetobacter pneumonia, one pneumonia with Succinivibrio spp. found in blood cultures, and one meningitis and transverse myelopathy with Streptococcus milleri found in blood cultures. CONCLUSIONS: The frequency, type and severity of infections in the relatively young patients result in high personal costs to the community and financial costs to the health care system. Standard preventive measures must be implemented to control severe bacterial infections among subjects with diabetes in this socially and economically marginalised population group. PMID- 1875834 TI - Reflotron cholesterol measurements in 1112 Australian children aged 10-12 years. AB - OBJECTIVE: To study the distribution of blood cholesterol concentration in a sample of Western Australian schoolchildren. DESIGN: The Reflotron dry-chemistry system (Boehringer Mannheim, Germany) was used to measure cholesterol in finger prick blood samples obtained from Year 6 children aged 10-12 years attending government schools in metropolitan Perth. Recruitment methods ensured that children from different socioeconomic strata were represented. PARTICIPANTS: For the 1239 children enrolled in Year 6 in 30 government schools, parental consent to participate was obtained for 1144; of these cholesterol concentration was measured in 1112. RESULTS: The measurement method proved practicable and was generally well accepted. Cholesterol levels were somewhat lower than those obtained using a laboratory reference method and a bias, relative to national quality assurance standards, was estimated to be -0.32 mmol/L. Mean cholesterol level in boys (4.28 mmol/L, SD 0.69) was not significantly different from that in girls (4.35 mmol/L, SD 0.72). Allowing for measurement bias, 52% of boys and 57% of girls had cholesterol levels exceeding the National Heart Foundation's designated "desirable" level of 4.5 mmol/L for children. CONCLUSIONS: The distribution of cholesterol levels in Australian children compares unfavourably with distributions in children in countries with low rates of cardiovascular disease and indicates a need for widespread, appropriate diet and lifestyle changes. PMID- 1875835 TI - Social, neurological and cognitive disorders in alcoholics. AB - OBJECTIVES: To construct the social, neurological and neuropsychological profiles of patients with suspected alcohol related brain damage, and to test the hypothesis that cognitive dysfunction develops in alcoholics before signs of alcohol related neurological disease. DESIGN: The study design comprised: a retrospective analysis of patients' records; a comparison of patients' demographic and social variables with age-matched population data from the 1986 Census; and a comparison of neuropsychological test scores of male patients with suspected alcohol related brain damage and age-matched controls. SETTING: The Neuropsychology Unit of Royal Prince Alfred Hospital, a tertiary referral teaching hospital. PARTICIPANTS: All patients (n = 641) referred to the Neuropsychology Unit for assessment of suspected alcohol related brain damage from July 1, 1987 to June 30, 1989, and a control group (n = 93) consisting of healthy volunteers who drank no more than 40 g of alcohol per day. RESULTS: Of the patients, 515 (80%) were men and 410 (64%) were 55 years or younger; their median daily alcohol consumption was 180 g. Compared with the general population the patients were significantly more likely to be in receipt of social security payments, to be separated, divorced or widowed and living in rented or temporary accommodation. However, the proportion of professional and skilled individuals was the same as in the general population. Cerebellar degeneration (38%), peripheral neuropathy (34%) and seizures (14%) were the most frequent neurological disorders. Frontal lobe dysfunction (58%) and short-term memory loss (32%) were the most frequent cognitive abnormalities. Dementia was relatively uncommon (4%). The mean age of male patients with alcohol related brain damage but no neurological disorders (43 years) was significantly less than the mean age of those with neurological disease (54 years; P less than 0.001). In the former, neuropsychological tests of frontal lobe function showed significant impairment compared with control subjects (P less than 0.001), despite normal intelligence. CONCLUSIONS: Cognitive impairment in alcoholics frequently takes the form of frontal lobe dysfunction and may be relatively subtle, requiring a neuropsychological examination for diagnosis. Signs of cognitive impairment may precede those of alcohol related neurological disorders by more than ten years. PMID- 1875836 TI - Personality and coping style as influences on alcohol intake and cigarette smoking during pregnancy. AB - OBJECTIVE: To determine if personality and coping style are central determinants of drinking and smoking at risk to fetal health during pregnancy. DESIGN, SETTING AND PARTICIPANTS: A sample of 99 women recently confined at a Sydney obstetric hospital received a semi-structured interview and completed a number of questionnaires. MEASURES: Alcohol and cigarette consumption over designated intervals since conception were assessed by interview. Questionnaires assessed maternal anxiety and postnatal depression, as well as coping strategies and personality characteristics such as impulsiveness. RESULTS: After confirmation of pregnancy, two-thirds of those previously drinking ceased while only one-third of those who had been smokers then abstained, with intake levels showing a similar pattern of a relatively greater decrease in alcohol than cigarette consumption over the course of the pregnancy. Personality and coping style differences were not demonstrated between the following contrasting groups: (a) smokers v. non smokers prior to confirmation of pregnancy; (b) on-going drinkers v. relative abstainers during pregnancy; and (c) excessive smokers and drinkers before pregnancy v. all other subjects. Comparison of drinkers and non-drinkers before pregnancy suggested less "mature" coping styles for the latter, an unexpected finding. CONCLUSION: There was little support for the hypothesis that drinking and smoking at risk to health (before and during pregnancy) are determined by the individual's personality and general coping repertoires. PMID- 1875837 TI - Persistent ductus arteriosus in adults. A review of surgical experience with 25 patients. AB - OBJECTIVE: To review the clinical features, operative details and course of adults with persistent ductus arteriosus. DESIGN: Retrospective study. Information on subjects was obtained by case records review. SETTING: The Cardiothoracic Unit, Royal Prince Alfred Hospital, Sydney. PATIENTS: Twenty-five adults aged 16 years and over with persistent ductus arteriosus, from 1974-1990. INTERVENTION: Surgical division or ligation of persistent ductus, via left thoracotomy or median sternotomy. MAIN OUTCOME MEASURES: Preoperative clinical features; postoperative mortality and morbidity. RESULTS: There was a high incidence of symptoms in this group of adults with persistent ductus arteriosus, many having anatomical (aneurysm, calcification) and/or haemodynamic (heart failure, pulmonary hypertension) complications. There was one death (mortality, 4%) of a young woman with significant preoperative pulmonary hypertension. The remaining 24 patients (96%) left hospital completely well between 4 and 12 days after surgery. CONCLUSIONS: Persistent ductus arteriosus, although primarily a paediatric problem, may present in adulthood. Closure by operative means (or in selected cases, by interventional catheter) is warranted in all adult subjects with left to right shunt, other than for patients over 60 years of age with neither heart failure nor cardiomegaly. PMID- 1875839 TI - Functional endoscopic sinus surgery. PMID- 1875838 TI - Principles behind practice. 8. Screening as a strategy for disease control. PMID- 1875840 TI - The confused patient. PMID- 1875841 TI - General practitioners' views of students: students' views of general practitioners. PMID- 1875842 TI - The Army Reserve. PMID- 1875843 TI - Thromboembolism and its management in pregnancy. AB - OBJECTIVES: To formulate recommendations for the management of thromboembolism during pregnancy. DATA SOURCES: The English language published literature derived from Medline and covering the following aspects of thromboembolism in pregnancy was reviewed: epidemiology; pathogenesis; clinical features; investigations; the pharmacology of various anticoagulants; management and prophylaxis of deep vein thrombosis and pulmonary embolism; medicolegal aspects. STUDY SELECTION: Publications published between 1960 and 1990 were cited. These studies were selected because data appeared reliable and with appropriate conclusions. DATA SYNTHESIS AND CONCLUSIONS: Many questions are still not completely resolved, but the information gathered should provide firm guidelines to practitioners in the areas of diagnosis, the choice of anticoagulant drugs, methods of administration of the drugs, and measurement of therapeutic endpoints. PMID- 1875844 TI - Westernisation, insulin resistance and diabetes in Australian aborigines. AB - OBJECTIVE: To examine the published data on the impact of westernisation on obesity, non-insulin dependent diabetes mellitus (NIDDM), and coronary heart disease (CHD) in Australian Aborigines. DATA SOURCES: Fifty-five articles from Australian and international sources (primarily peer-reviewed journals) are cited. STUDY SELECTION: Twenty-eight reports providing data on the diet, lifestyle, health and "lifestyle diseases" of Australian Aborigines before and after westernisation are included in this review. A further 27 articles on obesity, NIDDM, CHD, insulin resistance, and the impact of diet and exercise were used to help interpret the Aboriginal data. DATA EXTRACTION: Information on dietary composition, anthropometry, disease and risk factor prevalence, and relevant biochemical measurements were used for comparative and interpretive purposes. DATA SYNTHESIS: The traditional hunter-gatherer lifestyle of Australian Aborigines, characterised by high physical activity and a diet of low energy density (low fat, high fibre), promoted the maintenance of a very lean body weight and minimised insulin resistance. In contrast, for most Aborigines a Western lifestyle is characterised by reduced physical activity and an energy dense diet (high in refined carbohydrate and fat) which promotes obesity and maximises insulin resistance. When they make the transition from their traditional hunter-gatherer lifestyle to a westernised lifestyle, Aborigines develop high prevalence rates for obesity (with an android pattern of fat distribution), non-insulin dependent diabetes, impaired glucose tolerance, hypertriglyceridaemia, hypertension and hyperinsulinaemia. The striking improvements in carbohydrate and lipid metabolism in diabetic and non-diabetic Aborigines after a temporary reversion to a traditional hunter-gatherer lifestyle highlight the potentially reversible nature of the detrimental effects of lifestyle change, particularly in young people who have not yet developed diabetes. CONCLUSION: It is suggested that insulin resistance was important to the survival of Aborigines as hunter-gatherers, but is also the underlying metabolic characteristic predisposing them to obesity, NIDDM and CHD after westernisation. Intervention strategies to prevent chronic diseases related to insulin resistance should be directed at lifestyle modification. To be effective such programmes will have to be developed and implemented at the community level. PMID- 1875845 TI - A glossary of pain terms for medicolegal work. PMID- 1875846 TI - Propranolol overdose--a dramatic response to calcium chloride. AB - OBJECTIVE: To present a case of severe propranolol overdose which responded dramatically to the administration of calcium chloride. CLINICAL FEATURES: A 22 year-old female Caucasian who was unemployed arrived by ambulance to a hospital emergency department after propranolol overdose. She was convulsing and in electromechanical dissociation. An electrocardiogram showed sinus rhythm with broad QRS complexes. She had no relevant medical history. INTERVENTION: Resuscitation with basic and then advanced life support and administration of oxygen, adrenaline, atropine, fluids and bicarbonate gave no response. Calcium chloride, however, repeatedly produced a dramatic restoration of blood pressure and a narrowing of the QRS complexes. She made a good recovery with no sequelae. CONCLUSION: Calcium chloride may have a role to play in propranolol overdose. PMID- 1875847 TI - On living with rheumatoid arthritis. PMID- 1875848 TI - Detecting the cause of Lyme disease in Australia. PMID- 1875849 TI - Caffeine and disease. PMID- 1875850 TI - The AIDS test and preventive health care. PMID- 1875851 TI - AIDS. PMID- 1875852 TI - Quality assurance in health care. PMID- 1875853 TI - Chemical carcinogenesis--toluene? PMID- 1875854 TI - Methadone dosage and retention of patients in maintenance treatment. PMID- 1875855 TI - Surgical waiting list in Victorian hospitals. PMID- 1875856 TI - Flying Obstetric and Gynaecology service. PMID- 1875857 TI - On perpetuating a medieval tradition. PMID- 1875858 TI - Fatal cerebral haemorrhage after tiger snake bite. PMID- 1875859 TI - Human cutaneous anthrax. PMID- 1875860 TI - Idarubicin. PMID- 1875861 TI - Influenza vaccine, 1991-1992. PMID- 1875862 TI - [Heart involvement in mixed connective tissue disease (MCTD)]. AB - The incidence of cardial involvement in mixed connective tissue disease (MCTD) was investigated by two-dimensional echocardiography. Pericardial manifestation was found in two patients. Mitral valve prolapse was detected in 61% of the patients, which may indicate a specific cardial involvement in MCTD. Myocardial changes were rare. PMID- 1875863 TI - [Somatomedin C level and stimulation of growth hormone and adrenal cortex function by administration of releasing hormones and physical exertion in patients with obesity]. AB - In a clinical study on potential determinants underlying the impairment of growth hormone stimulation in obese human subjects, we examined in 20 otherwise healthy adult obese subjects (14 females, six males, age 18 to 40 years, body mass index greater than 29 kg/m2) the responses of growth hormone (hGH), adrenocorticotropic hormone (ACTH) and cortisol to releasing hormone stimulation (growth hormone releasing hormone and corticotropin-releasing hormone) and the responses of hGH, ACTH, cortisol and free fatty acids (FFA) to physical exercise. Subjects with somatomedin-C levels less than or equal to 0.7 U/ml (group 1) were more obese than subjects with somatomedin-C levels greater than 0.7 U/ml (group 2) (p less than 0.01). In group 1, hGH increased by 4.3 +/- 1.2 ng/ml in response to releasing hormone administration and by 0.9 +/- 0.3 ng/ml in response to physical exercise (normal responses, increase by greater than 7 ng/ml), in group 2, hGH increased by 6.7 +/- 1.4, and 2.4 +/- 0.8 ng/ml, respectively (p less than 0.05 vs. group 1). Moreover, FFA stimulation by physical exercise was blunted in group 1 (p less than 0.05 vs. group 2). In contrast, ACTH stimulation was found increased in group 1 in comparison to group 2, particularly in response to physical exercise (p less than 0.01), and resulted in enhanced cortisol stimulation (p less than 0.05). Thus, impaired hGH stimulation in obese human subjects is not explained by an altered relationship between hGH and somatomedin C levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1875864 TI - [Port-catheter perforation into the duodenum and other early complications after port implantation before intra-arterial infusion therapy of the liver with chemotherapeutic drugs]. AB - Early complications following implantation of intraarterial hepatic port catheter systems from 1985 to 1988 in 24 patients are reported with special view to the perforation of a port catheter into the duodenum. In this case the primary postoperative angiographic control four weeks after implantation showed correct placement and perfusion of the liver. The perforation occurred before starting any cytostatic regimen. We observed a total of 21% irregularities and complications: dislocation of port membrane (n = 1), incorrect catheter displacement but regular liver perfusion (n = 1), catheter leakage (n = 1), subhepatic abscess (n = 1) and perforation of the catheter in the duodenum. When possible we combine port-implantation with resection of the liver. PMID- 1875865 TI - [Portal hypertension in childhood. Freiburg gastroenterology conference]. PMID- 1875866 TI - [Intermittent ventilation--a new therapy in chronic respiratory failure]. PMID- 1875867 TI - [Therapeutic concept in ovarian cancer]. PMID- 1875868 TI - [Should a patient use self-ventilation?]. PMID- 1875869 TI - [Responsibilities of the physician in "Rehabilitation 2000"]. PMID- 1875870 TI - [Castleman tumor as differential diagnosis of unilateral hilus enlargement]. PMID- 1875871 TI - [Mediators in purulent meningitis]. PMID- 1875872 TI - The black bag. PMID- 1875873 TI - Addicted docs. Care givers who need care. PMID- 1875874 TI - The successful treatment of psychogenic polydipsia and water intoxication with propanolol. A case report. AB - Psychogenic polydipsia (PPD), which can lead to water intoxication (WI), is a problem with many psychiatric patients. The case history of one schizophrenic patient presented here shows that propanolol therapy can reduce PPD and WI, possibly decrease thirst, and improve schizophrenic symptoms and behavior. When combined with regular weight evaluation and behavioral treatment to restrict water intake, the therapy can further reduce the risk of developing life threatening WI complications. PMID- 1875876 TI - Pill for AIDS-related pneumonia. PMID- 1875875 TI - Right-to-die issues in Minnesota. PMID- 1875877 TI - HIV infection in the medical work place. Are physicians and patients at risk? PMID- 1875878 TI - HIV infection in the health care setting. Putting the risk in perspective. PMID- 1875879 TI - Neonatal seizures: an overview. AB - Seizures in the newborn are different from those occurring in older children and adults. Health care professionals may find it difficult to recognize neonatal seizures because of their sometimes subtle manifestations. Convulsive behavior has many etiologies; some are associated with a favorable and some with a poor prognosis. Treatment protocol is controversial because both the seizures themselves and the drugs used to treat them may damage the immature brain. The high mortality and morbidity rates of infants who experience seizures make it imperative that the neonatal seizure be recognized, its etiology diagnosed, and treatment begun promptly. PMID- 1875880 TI - What is an organized infant? AB - Organization is a term used to describe the establishment of integrated functioning between an infant's physiologic and behavioral systems. When these systems are well integrated, the infant is able to interact with the environment without disruptions in autonomic, motor, and state functioning. As a result, he will not experience alterations in vital signs, color, state, or digestive functions that may compromise his future growth and development. Infants who can maintain or regain physiologic and behavioral organization will conserve energy for growth, provide caregivers with clear behavioral cues that indicate their needs, facilitate the establishment of parent-infant attachment, and use self consoling or habituating behaviors when interacting with an environment that is too stimulating. As a result, developmental outcomes can be enhanced, particularly in infants who are at risk for neurobehavioral sequelae and developmental delays. Nurses can help infants achieve and maintain organization by providing an environment that supports their physiologic and behavioral organization. PMID- 1875881 TI - Genetic risks and other hazards for the NICU nurse. PMID- 1875882 TI - Documentation: short, simple, and meaningful. AB - Nursing diagnosis has been incorporated into the documentation in our neonatal units because it gives nurses credit for their unique functioning, provides for consistency in communication, facilitates continuity of care, and is therefore likely to improve the quality of nursing care. The documentation system utilizes flow sheets to document physiological functioning. The nursing progress note/individualized patient care plan provides for a narrative note and continuous update of the patient care plan, keeping it current and meaningful. Previous care plans have involved massive writing about nursing actions. By providing reference tools that list the actual nursing actions, this system allows the nurse's written documentation to describe what the focus of the nurse's work has always been: the patient and the patient's responses to nursing care. PMID- 1875883 TI - United States Maternal and Child Health Services. Part II: a comparison with Western Europe and strategies for change. AB - Part I of this article showed that accessibility and quality of health care in the United States is determined by race, language, national origin, income level, education, age, and location of residence; that there is consistent correlation of low income with inaccessibility to perinatal care and poor pregnancy outcome; and that certain traditional American values are in part responsible. Despite many well-designed programs, the existing system of maternal-child health care delivery in the U.S. remains an overly complex, fragmented, and fundamentally flawed network fraught with financial and institutional obstacles to care. Major health indices, such as infant mortality rate and teenage pregnancy rate, attest to the fact that our system is failing. PMID- 1875884 TI - Corporate funding: resource for neonatal nursing research. PMID- 1875885 TI - Education in the NICU: an introduction. PMID- 1875886 TI - Vancomycin. PMID- 1875887 TI - Standards enhance program quality. PMID- 1875888 TI - Experiences of a Navy nurse in the Middle East. PMID- 1875889 TI - [Diagnostic significance of urinary endothelin concentration]. AB - We investigated plasma Endothelin concentration (s-ET) and urinary Endothelin concentration (u-ET) in eleven patients undergoing subtotal esophagectomy through r-thoracal and abdominal approach for esophageal cancer (nine men and two women). S-ET and u-ET, sodium excretions fraction (FENa), free-water clearance (CH2O, uric NAG Index, creatinine clearance rate (Ccr), primary water balance (PWB) and primary sodium balance (PNB) were measured during the perioperative period till the 7th day. Urinary Endothelin concentration in the postoperative 3 and 6 hours, and the 2nd postoperative day were significantly higher than preoperative value. No significant values were obtained in plasma Endothelin Highly significant correlations were obtained between urinary Endothelin concentration and FENa, CH2O, PWB and PNB. Furthermore, u-ET was well correlated with s-ET. We concluded that the measurement of u-ET may be useful as an indicator of renal tubular function and global renal functions with high sensitivity. PMID- 1875890 TI - [Effect of transfusion of blood components on gastric cancer patients--special reference to the incidence of postoperative hepatitis and prognosis]. AB - To evaluate the effect of blood transfusion on incidence of postoperative hepatitis and prognosis of gastric cancer, the data of 493 patients having been operated on curatively in our hospital were divided into two groups: those who received transfusion before the beginning of components transfusion and those who received transfusion after that. The data indicated that the incidences of postoperative hepatitis increased from 3.7% to 5.4% after the beginning of transfusion of blood components, but the 5-year survival rates did not differ significantly. The 5-year survival rates of transfused patients and non transfused patients were 57%, 84%, respectively (p less than 0.001) and the rates decreased according to the dose of whole blood and/or packed red cells. The same results were obtained when limited to stages I + II, But they were not deteriorated by fresh frozen plasma significantly. The result suggests that it is better to refrain from unnecessary blood transfusion and transfuse whole blood in the case of massive transfusion to decrease the incidence of postoperative hepatitis and more better to transfuse leucocyte-free blood to avoid immunological effect. PMID- 1875891 TI - [Studies on the clinical evaluation of tissue polypeptide antigen (TPA) levels in the peripheral and draining venous blood of gastric cancer patients]. AB - Correlation with TPA levels of peripheral (p) and draining (d) venous blood, and 11 histopathologic variables, postoperative recurrence and survival was examined in 40 patients with gastric cancer. Elevation of d-TPA levels was correlated with tumor location, size, macroscopic type, invasive layer of gastric wall, venous invasion, node and liver metastases and stage classification, though elevation of p-TPA levels was correlated only with liver metastasis. No significant difference of p-TPA levels was found between the patients with and without cancer recurrence. d-TPA levels (mean 1318U/l and positive rate greater than 726U/l of mean +/- 2SD in patients with benign diseases, 59%) of the former were significantly higher than those (518U/l and 15%) of the latter. Correlation between d-TPA levels and recurrent sites was not found. Most of the patients with hematogenous recurrence showed the elevated p-TPA levels, but none of the patients with local recurrence revealed the elevation. Survival in both patients with non-elevated p- and d-TPA levels was significantly better than in patients with the elevated levels. These results suggest d-TPA levels are more closely correlated with histopathologic variables and postoperative recurrent rates than p-TPA levels, preoperative determination of p- and d-TPA levels is useful for the estimation of the postoperative prognosis and patients with elevated p- and d-TPA levels should be clinically treated as patients with high recurrence and poor prognosis. PMID- 1875892 TI - [Analysis of factors relating to early repairment of the surgical margin following liver resection--factors relating to duration of hospital stay]. AB - To analyze relating factors to early repairment of the surgical margin of the remnant liver we measured plasma fibronectin (FN), coagulation factor XIII (XIII), polymorphonuclear leukocyte elastase (PMNE), platelet counts (Plt), prothrombin time (PT%) before and at the first, third, 7th and 14th days after liver resection in 25 patients. Changes in these factors (1) were compared with their clinical status, such as liver cirrhosis, high fever, abscess formation, duration of drainage and use of microwave tissue coagulator (MTC) (2). The multivariate analysis about the factors influencing the duration of hospital stay (3) were carried out. (1) In the all cases FN, XIII (14th), PT%, Plt decreased and PMNE increased significantly versus pre-operative data. There were significant correlations between FN and XIII, FN and PMNE. (2) In the cirrhotic group FN, XIII, PT% and Plt were significantly lower than those of non cirrhotic group. In the abscess formation group PT% was significantly lower than the no abscess formation group. In the MTC group XIII, PT% and Plt were significantly lower than those of the no-MTC group. In conclusion, FN, XIII, Plt and PT% in the cirrhotic, high fever, abscess formation or longer drainage group were in lower levels compared with the each control group. (3) By the multivariate analyses, abscess formation, high fever and liver cirrhosis were the most influencing factors for the duration of hospital stay. PMID- 1875893 TI - [Functional and morphological changes of the liver after brain death maintained with the combined administration of vasopressin and catecholamine]. AB - We investigated the functional and morphological changes of the liver after brain death for long period maintained with the combined administration of arginine vasopressin (ADH) and catecholamine. Twenty five brain-dead patients suffered from severe closed head injury were studied. The average age was 38.2 y.o. Systemic circulation was maintained normal for at least 6 days with ADH and catecholamine. ADH was infused constantly with an average dosage of 0.3 mU/kg/min. Simultaneous infusion of catecholamine was adjusted to maintain the mean arterial pressure above 80 mmHg. The morphological changes were not remarkable in the liver cells throughout the study. Levels of activated partial thromboplastin time (APTT) except in 5 patients remained within normal range for two weeks. According to this data, it can be considered that there is no marked lowering in the activity of protein synthesis of the liver. The progressive increase of serum alkaline phosphatase, LAP, gamma-GTP, and total bilirubin were observed as the characteristic changes of the liver after brain death. Serum levels of total bilirubin were markedly elevated especially in the patients who received massive transfusion. Histologically, cell infiltration into the Glisson's sheath became remarkable in all cases as day proceeded. These findings suggest the dysfunction of bile excretion might occur due to the denervation from the brain. PMID- 1875894 TI - [Effect of glucagon and insulin on the histochemical and functional alterations in the Langerhans islands after hepatectomy in dogs]. AB - Changes of Langerhans islands after 40% hepatectomy, and effects of GI therapy on the islets were investigated in dogs. In control group, one week and four weeks after the hepatectomy, ivGTT was examined followed by a blood sampling from the portal vein to measure the changes of glucose, insulin and glucagon, and areal changes of the islets were measured. In GI group, the same experiment was done with added GI therapy after operation. The following results were obtained. 1) In control group, portal plasma insulin level and insulin response were decreased one week after surgery, and sizes of islets were enlarged four weeks after surgery. 2) In GI group, there were no decrease in portal plasma insulin level and insulin response one week after surgery, and no enlargement of the sizes of the islets four weeks after surgery. 3) Changes in glucagon level and glucagon response were same as those of insulin, glucose level and these response. There was no difference between the two groups. 4) According to these observation, glucagon and insulin are exhausted one week after hepatectomy in dogs. It seems to be necessary to provide the dog with glucagon and insulin after hepatectomy. PMID- 1875895 TI - [Effect of LAK cells on liver regeneration after partial hepatectomy]. AB - Lymphokine activated killer (LAK) cells can destroy not only tumor cells but also syngeneic regenerating liver cells. This study was started to determine the effect of passive transfer of LAK cells on liver regeneration after partial hepatectomy. C3H mice were received 70% hepatectomy and LAK cells were injected intravenously at a dose of 5 X 10(7) cells/body. After 36 hours, 3H-thymidine uptake into the residual liver was measured. LAK cells transferred group showed 31% suppression compared with control group. In vitro, 24 hours addition of LAK cells to the primary culture of regenerating liver cells caused 97% suppression of 3H-thymidine uptake at effector to target ratio, 50/1. Then we examined the effects of IL-2 administration on liver regeneration. Though IL-2 showed no effect on cultured liver cells, intraperitoneal administration of IL-2 after hepatectomy at a dose of 1 X 10(4)u/body 5 times every 8 hours brought 38% suppression of 3H-thymidine uptake of the residual liver. Cyclosporine A, which can suppress the IL-2 production of lymphocytes, promoted liver regeneration 45% over the control at a dose of 10 mg/kg. These results suggest that LAK cells could regulate liver regeneration. PMID- 1875896 TI - [Experimental study of endotoxemia and reticuloendothelial system in hepatectomized cirrhotic rats]. AB - To investigate acute hepatic failure associated with endotoxemia and reticuloendothelial system (RES) in hepatectomized cirrhotic patients, lipopolysaccharide (LPS) at the dose of 0.2 micrograms/100gBW was injected intravenously into the 70% hepatectomized three groups of rats as follows; LC: rats with thioacetamide-induced liver cirrhosis, CONTROL: rats with normal liver, LC + FN: cirrhotic rats with intravenous supplementation of fibronectin. 1) The survival rates at 24 hours after hepatectomy of each group of LC, CONTROL and LC + FN were 0%, 100%, and 80%, respectively. Residual liver of group-LC revealed massive necrosis in histological study. 2) Phagocytic index (K) of injected 3H labeled LPS were 0.100/min, 0.155/min and 0.146/min, respectively. 3) Uptake of injected 3H-labeled LPS at 15 minutes after injection was remarkably elevated into the liver compared with the lung and spleen in each group. Also uptakes into the liver per gram of tissue were 0.96% ID/g, 3.00% ID/g and 1.46% ID/g, respectively, and those per total organ were 5.95% ID/TO, 8.20% ID/TO and 9.21% ID/TO, respectively. 4) Level of plasma fibronectin decreased and that of serum total bile acid increased remarkably after injection of LPS in group-LC compared with the others. These results suggest the mortality of hepatic necrosis by LPS in group-LC is attributed to markedly reduced RES function especially in the liver, and supplementation of fibronectin decreases the mortality by enhancing RES function. PMID- 1875897 TI - [The growth rates of liver metastases in pancreatic cancer--comparison on growth rates between clinical cases and established human pancreatic cancer cell lines]. AB - By measuring the doubling time both of clinical liver metastases and cultured human pancreatic cancer cell lines, we studied the possibility of occult liver metastases at the time of pancreatectomy in patients with pancreatic cancer. Doubling times of 3 pancreatic cancers were obtained from the measurements of size of liver metastases after pancreatectomy and those were compared with those of cultured human pancreatic cancer cell lines established from two of these cases. Doubling time of liver metastases were about fifteen times as long as those of cultured cell lines. On the assumption that growth rates of liver metastases were constant, the size of liver metastases at the time of pancreatectomy was calculated in three cases. The calculated sizes of these liver metastases were 140 microns, 2.4 mm, and 8.3 mm respectively. These results indicate that occult liver metastases have already existed in patients with pancreatic cancer even though they were clinically undetectable at the time of operation. And some adjuvant therapies against occult liver metastases are necessary for achievement of the better prognosis. PMID- 1875898 TI - [Immunologic function against infection in splenic autotransplanted mice]. AB - The increasing recognition of the danger of overwhelming postsplenectomy infection (OPSI) has led surgeons to attempt to maintain splenic function after spleen injury. One technique they use when splenorrhapy or partial splenectomy are not feasible is the deliberate autotransplantation of splenic tissue. But the amount of splenic tissue necessary to prevent OPSI remains controversial, and opinions differ about the importance of the location and size of the splenic fragments implanted. The mice were divided into five groups, I. splenectomy, II. splenectomy +30% of the spleen implanted intraperitoneal site, III. splenectomy +50% implanted intraperitoneally, IV. splenectomy +50% implanted subcutaneously and V. Sham operation. This study assessed the blood flow of the splenic tissue, increasing weight of splenic mass, histology, the serum level of the immunoglobulins (IgG, IgA, and IgM), pneumococcal antibody titers after vaccination, and survival after intravenous pneumococcal challenge. This study demonstrated that intraperitoneal transplantation showed better regeneration and afforded better protection from OPSI than subcutaneous transplantation. And 30 to 50 percent of the whole splenic tissue mass protected against experimental pneumococcal sepsis. The splenic autotransplants developed in volume and blood supply after 8 weeks, and immunologic function against infection recovered at the same time. PMID- 1875899 TI - [Cerebral infarction after coronary artery bypass surgery--its cause, management and prevention]. AB - Among 535 cases of simple CABG, cerebral infarction was complicated in 5 cases (0.9%). Their mean age (65.2 years old) was high, and 80% of them had the history of hypertension or diabetes mellitus or both. The causes of the cerebral infarction were considered to be the embolism of atheromatous debris from the ascending aorta (3 cases), the cerebral hypoperfusion due to cerebral arterial disease and hypotension during cardiopulmonary bypass (1 cases), and the embolism of the left atrial thrombus formed during repeated supraventricular tachyarrhythmias (1 case). Both cases of the multiple infarctions were lost in hospital 10 months and 21 months postoperatively. Two of the three cases of single infarction suffered from the permanent neurological deficits. To prevent cerebral infarction which might totally deprive of the efficacy of the CABG, it is important to check and properly manage the atheromatous change of the ascending aorta, the cerebral arterial disease, and also postoperative supraventricular tachyarrhythmias. PMID- 1875900 TI - [Interaction of lung cancer cells and fibroblasts]. AB - Fibroblasts are found to secrete several factors, but complex interactions between cancer cells and fibroblasts are not well known. In this report, it was discussed how fibroblasts derived from lung cancer tissues affected lung cancer cells in vitro and in vivo. As results, the growth of 4 of eight cancer cells was promoted by any medium conditioned by fibroblasts (C.M) in vitro. Fifty percent of the 12 fibroblasts had some effect on promoting the growth of cancer cells, but had no effect on suppressing cancer cells. The C.Ms promoting the growth of cancer cells in vitro exerted the same effect in nude mice, too. Coinoculation of fibroblasts and cancer cells into nude mice gained higher tumorigenicity than cancer cells alone with no relation to their subclasses. It was suggested that to examine the effect on promoting the growth of cancer cells by fibroblasts derived from lung cancer tissues in vitro was able to prospect how fibroblasts affected cancer cells in vivo and fibroblasts made some good condition to transplanted cancer cells into nude mice by means different from growth factors. PMID- 1875901 TI - [Proliferative activity assessed on the basis of DNA ploidy patterns in primary lung cancer]. AB - Flow cytometric cellular DNA-RNA content analysis by acridine orange staining was conducted on surgical fresh specimens of primary lung carcinomas from 66 patients (31 squamous cell carcinomas, 34 adenocarcinomas and 1 large cell carcinoma). The frequency of aneuploid tumors was 84.6% among the tumors. RNA content (RNA Index) in the DNA aneuploid tumor much more significantly (p less than 0.05) increased than the DNA diploid tumor. Tumor doubling time in the DNA aneuploid tumor was significantly (p less than 0.05) shorter than in the DNA diploid tumor. In the patients with lung cancers that recurred within 1 years, recurrence of the DNA aneuploid tumor was higher than the DNA diploid tumor. It is evident from the above results that proliferative activity in the DNA aneuploid tumor increases much more than in the DNA diploid tumor. This in turn may induce early recurrence in patients with lung cancer. PMID- 1875902 TI - [Acute occlusion of the iliac arteries due to blunt trauma]. AB - Two cases of acute iliac occlusion due to blunt trauma are presented. The cause of injuries were a fall from bicycle in case 1 and a compression between an automobile and a wall in case 2. The end-to-end anastomosis was possible in case 2, but an interposition of an artificial prosthesis was necessary because of the length of damaged artery in case 1. Both cases were associated with the pelvic fracture, adding the perforation of small bowels and the bladder in case 2. Postoperative course was almost uneventful except fasciotomy was needed for the compartment syndrome of the right lower extremity in case 2. PMID- 1875903 TI - [A case report of cystic adventitial degeneration communicating with the hip joint in the external iliac artery]. AB - Cystic adventitial degeneration is an uncommon cause of arterial obstruction. Its etiology is debated. We report a case in which the left external artery was affected and the cystic mass communicated with the hip joint. The findings of this case support the embryonic theory that the articular synovium and adventitial cysts have the same mesenchymal origin. PMID- 1875904 TI - [Cardiovascular effects of increased intra-abdominal pressure during pneumoperitoneum: preliminary report]. PMID- 1875905 TI - [Study of stroma promoting factor on carcinoma cell using alginic acid microcapsule: preliminary report]. PMID- 1875906 TI - [Xenotransplantation in diabetic rats: adult pig islet isolation: preliminary report]. PMID- 1875907 TI - Mechanism of nerve growth factor mRNA regulation by interleukin-1 and basic fibroblast growth factor in primary cultures of rat astrocytes. AB - Neonatal rat cortical astrocytes in primary culture synthesize and secrete nerve growth factor (NGF). Interleukin-1 beta(IL-1) and basic fibroblast growth factor (bFGF) treatment of astrocytes increased NGF mRNA content by about 2-fold. The effect of these two factors was specific, because other growth factors, such as tumor necrosis factor-alpha, insulin-like growth factor-1, and epidermal growth factor, failed to change NGF mRNA content. The concentrations of IL-1 and bFGF causing half-maximal stimulation were 1 unit/ml and 1 ng/ml, respectively. The increase in NGF mRNA elicited by IL-1 and bFGF was maximal at 3 hr of incubation. In the presence of IL-1 this increase persisted for 36 hr, whereas in the presence of bFGF the initial increase in NGF mRNA was followed by a decrease to 50% of control levels after 24 hr of incubation. Readdition of bFGF after 24 hr of treatment gave a similar increase in NGF mRNA content, suggesting that the decrease at 24 hr was not due to receptor desensitization. The effect of IL-1 was reversible, because removal of IL-1 after 3 hr of incubation resulted in a decrease of NGF mRNA content to control levels by 6 hr, whereas a readdition of IL-1 at this time led to a 2-3-fold increase in NGF mRNA content after an additional 3 hr of treatment. This second increase in NGF mRNA was also maintained for several hours. The combined treatment of astrocytes with maximally effective doses of IL-1 and bFGF produced an additive increase in NGF mRNA content, suggesting that different mechanisms are operative. Treatment of astrocytes with cycloheximide increased (about 6-fold) NGF mRNA content, and this content failed to increase further with IL-1 or bFGF treatment. Experiments using actinomycin D indicated that IL-1 increased the stability of the NGF mRNA. bFGF treatment failed to change this parameter. Thus, IL-1 increases NGF mRNA content in astrocytes, at least in part, by stabilizing mRNA, whereas bFGF does not affect mRNA stability but may act at the level of NGF gene transcription. PMID- 1875908 TI - Hormonal regulation of microsomal flavin-containing monooxygenase: tissue dependent expression and substrate specificity. AB - The substrate- and tissue-dependent hormonal regulation of flavin-containing monooxygenase (EC 1.14.13.8) was studied in male and female rats. Hypophysectomy of males reduced liver microsomal N,N-dimethylaniline N-oxidation, thiobenzamide S-oxidation, and imipramine N-oxidation, although the reduction was not as marked with the latter substrate. Castration also reduced flavin-containing monooxygenase-dependent activities, but not to the same extent as hypophysectomy. Administration of growth hormone or testosterone to hypophysectomized males only partially restored basal activities. In female rats, hypophysectomy had no effect on N,N-dimethylaniline N-oxidation or thiobenzamide S-oxidation and actually stimulated imipramine N-oxidation (98%). These effects were demonstrated to be tissue- and sex-dependent. For example, hypophysectomy markedly (300%) enhanced imipramine N-oxidation in male kidney and significantly decreased the same activity in male and female lung. Correlations between levels of the enzyme determined by immunoquantitation (with antibody to the rat liver enzyme) and activities toward these three substrates, in male and female liver, lung, and kidney, also provide evidence for the existence of multiple forms of flavin containing monooxygenase, which appear to be under different hormonal regulation. PMID- 1875909 TI - Molecular genetic basis of rapid and slow acetylation in mice. AB - The molecular genetic basis of N-acetylation polymorphism has been investigated in inbred mouse models of the human acetylation polymorphism. Two genomic clones, Nat1 and Nat2, were isolated from a C57BL/6J (B6) mouse (rapid acetylator) genomic library. The Nat1 and Nat2 genes both have intronless coding regions of 870 nucleotides and display greater than 47% deduced amino acid similarity with human, rabbit, and chicken N-acetyltransferases. Amplification of Nat1 and Nat2 from A/J (A) mouse (slow acetylator) genomic DNA by the polymerase chain reaction and subsequent sequencing revealed that Nat1 was identical in B6 and A mice, whereas Nat2 contained a single nucleotide change from adenine in B6 to thymine in A mice. This nucleotide substitution changes the deduced amino acid at position 99 from asparagine in B6 to isoleucine in A mice. Hydropathy analysis revealed that this amino acid change alters the hydropathy of the flanking peptide segment in NAT2 from hydrophilic in the B6 mouse to hydrophobic in the A mouse. The amino acid change occurs in a region of the gene where no polymorphism has yet been reported in human or rabbit NAT2 and may represent an important structural domain for N-acetyltransferase activity. Nat1 and Nat2 have the same 5' to 3' orientation in the B6 mouse; the two genes are separated by approximately 9 kilobases, with Nat1 located 5' of Nat2. PMID- 1875910 TI - Purification and characterization of the major hepatic cannabinoid hydroxylase in the mouse: a possible member of the cytochrome P-450IIC subfamily. AB - Acute cannabidiol treatment of mice inactivated hepatic microsomal cytochrome P 450IIIA (P-450IIIA) and markedly inhibited in vitro cannabinoid metabolism. Antibodies raised against purified P-450IIIA inhibited the microsomal formation of quantitatively minor cannabinoid metabolites but had no effect on the major metabolites. Cannabinoid hydroxylation to the major metabolites was used as a functional probe to isolate and purify a P-450 (termed P-450THC) from hepatic microsomes of untreated mice. The purified protein had an apparent molecular weight of 47,000 and a specific content of 15.4 nmol/mg and exhibited an absorbance maximum at 452 nm for the reduced carbon monoxide complex. NH2 terminal sequence analysis of the first 16 residues of P-450THC suggests that it is a member of the P-450IIC subfamily, because its sequence is 85 and 69% identical to published sequences of rat hepatic P-450IIC7 and P-450IIC6, respectively. P-450THC exhibited high activity for cannabinoid hydroxylation and specifically produced 6 alpha- and 7-hydroxy-delta 1-tetrahydrocannabinol, as well as 6 alpha-, 7-, and 4"-hydroxycannabidiol. Unlike anti-P-450IIIA antibody, antibody raised against purified P-450THC markedly inhibited the microsomal formation of all major cannabinoid metabolites. Similar immunoinhibition studies also revealed the existence of orthologs of mouse P-450THC and P-450IIIA in human liver microsomes. Thus, cannabidiol treatment of mice resulted in the inactivation of at least two constitutive P-450 isozymes, which together account for the majority of the detected cannabinoid metabolites. PMID- 1875911 TI - Role of inositol (1,4,5)trisphosphate in epidermal growth factor-induced Ca2+ signaling in A431 cells. AB - The effects of epidermal growth factor on Ca2+ signaling in A431 cells were investigated. Epidermal growth factor induced a transient Ca2+ signal in the absence of external Ca2+ and a sustained response in the presence of extracellular Ca2+, indicating an ability to mobilize intracellular Ca2+ as well as the ability to increase Ca2+ entry from the extracellular space. The Ca(2+) ATPase inhibitor thapsigargin also activated Ca2+ entry, and neither epidermal growth factor nor the guanine nucleotide-dependent protein-linked receptor agonist bradykinin activated additional Ca2+ entry over that due to thapsigargin. In nominally Ca(2+)-free medium, the addition of bradykinin to A431 cells rapidly but transiently increased inositol 1,4,5-trisphosphate and, in parallel fashion, transiently increased cytosolic Ca2+. Unexpectedly, under these experimental conditions, epidermal growth factor elicited a small but significant Ca2+ signal after the addition of bradykinin. Experiments were designed to determine whether the Ca2+ response to epidermal growth factor after bradykinin results from mobilization of Ca2+ by an inositol 1,4,5-trisphosphate-independent mechanism. Epidermal growth factor stimulated additional inositol 1,4,5-trisphosphate formation in bradykinin-treated cells. Furthermore, the Ca2+ signals elicited by both bradykinin and epidermal growth factor were blocked in cells microinjected with the inositol 1,4,5-trisphosphate receptor antagonist heparin, whereas the intracellular Ca(2+)-ATPase inhibitor thapsigargin still mobilized Ca2+. Finally, histamine, a less efficacious guanine nucleotide-dependent protein-linked receptor agonist, as well as photolyzed, microinjected, caged inositol 1,4,5 trisphosphate, also mobilized Ca2+ after bradykinin. The results of this study show (i) that epidermal growth factor activates intracellular Ca2+ release as well as Ca2+ entry, the latter most likely resulting from an indirect effect due to the depletion of intracellular Ca2+ pools, (ii) that the actions of epidermal growth factor on Ca2+ homeostasis can be fully accounted for by inositol 1,4,5 trisphosphate formation, and (iii) that the ability of A431 cells to produce Ca2+ signals when epidermal growth factor is applied after bradykinin can be explained by the rapid and complete desensitization of the bradykinin stimulated phospholipase C activity. PMID- 1875912 TI - Agonistic activities of histamine-albumin conjugates at histamine H2 receptors on human HL-60 promyelocytic leukemia cells. AB - We previously identified functional histamine H2 receptors on human HL-60 promyelocytic leukemia cells [J. Biol. Chem. 264: 18356-18362 (1989)]. In the present study, we have compared the action of histamine-albumin conjugates on H2 receptor activation with that of histamine alone. Both histamine and conjugates increased intracellular levels of Ca2+ in an H2 receptor-specific manner. However, binding of fluoresceinated histamine-albumin conjugates to HL-60 cells was not dissociated by 10(-4) M unlabeled histamine, although this concentration of histamine significantly desensitized conjugate responses. These data suggest that histamine-albumin conjugates not only activate H2 receptors but also bind to HL-60 cells nonspecifically or in an H2 receptor-unrelated manner. Moreover, histamine-induced Ca2+ mobilization was transient, whereas conjugate-induced Ca2+ mobilization was sustained for more than 10 min, as a result of the influx of extracellular Ca2+. Therefore, the functional difference between histamine and conjugates may provide a good model for the further understanding of the activation mechanisms of receptor-operated Ca2+ influx. PMID- 1875913 TI - Patterns of internal and external tetraethylammonium block in four homologous K+ channels. AB - Tetraethylammonium (TEA) is a small ion that is thought to block open K+ channels by binding either to an internal or to an external site. For this reason, it has been used to probe the ion conduction pathway or pore of K+ channel mutants and a K+ channel chimera. The results suggested that the region between transmembrane segments 5 and 6 (S5-S6 linker) was involved in the formation of both the internal and the external TEA binding sites and the K+ conduction pathway. Therefore, we compared internal and external TEA block of the currents expressed in Xenopus oocytes injected with RNAs from four related K+ channel clones, DRK1, RCK1, RCK2, and r-NGK2, which have only subtle structural differences in the S5 S6 linker. r-NGK2 was the most sensitive to external TEA and the least sensitive to internal TEA application. For DRK1 the profile was reversed. RCK1 was blocked equally well from either side, whereas RCK2 was more strongly blocked by internal TEA. The internal block was voltage dependent, whereas the external block was virtually voltage independent. As predicted from block of whole-oocyte currents, internal TEA produced a slow block of DRK1 and RCK2 single-channel currents but had almost no effect on r-NGK2 single-channel currents. Tetrapentylammonium produced a stronger block than TEA at the internal site, and the block was relieved by inward K+ currents, therefore suggesting that the internal TEA binding site is located within the K+ conduction pathway. These results, together with the TEA block of single-channel currents, establish what has until now been inferred by extrapolation from other studies, i.e., that TEA is an open-channel blocker in K+ channel clones. DRK1 mutants with extensive amino- and carboxyl terminal deletions showed the same blocking profile as the parent DRK1. We conclude that TEA blocks these K+ channels at two sites, which define the inner and outer mouths of the channel pores. Comparison of the primary amino acid sequences in the S5-S6 linker suggests which residues may be responsible for the different patterns of TEA block. PMID- 1875914 TI - Role of the steroid 17 alpha-hydroxylase in spironolactone-mediated destruction of adrenal cytochrome P-450. AB - Previous investigations have established that spironolactone (SL) is converted to a reactive metabolite by adrenal microsomal enzymes, resulting in the degradation of cytochrome P-450 (P-450). Deacetylation of SL to 7 alpha-thiospironolactone (7 alpha-thio-SL) is the first step in the activation pathway, but further NADPH dependent metabolism of 7 alpha-thio-SL is required for P-450 destruction. Studies were done to evaluate the role of the steroid 17 alpha-hydroxylase in the activation of 7 alpha-thio-SL by adrenal microsomes. Incubation of guinea pig adrenal microsomes with 7 alpha-thio-SL in the presence of NADPH effected greater than 50% declines in P-450 content and in 17 alpha-hydroxylase activity but no change in the rate of 21-hydroxylation. Preincubation of the microsomes with antisera to the 17 alpha-hydroxylase P-450 isozyme (P-450(17 alpha,lyase)) decreased 17 alpha-hydroxylase but not 21-hydroxylase activity and prevented the degradation of P-450 by 7 alpha-thio-SL. Control IgG had no effect on 17 alpha hydroxylase activity or on the 7 alpha-thio-SL-mediated destruction of P-450. When added to a purified P-450(17 alpha,lyase) preparation, 7 alpha-thio-SL and the endogenous substrate progesterone caused typical type I spectral changes, but SL did not. Incubation of a purified and reconstituted 17 alpha-hydroxylase system, consisting of P-450(17 alpha,lyase), NADPH-P-450 reductase, cytochrome b5, and dilauroylphosphatidylcholine, with 7 alpha-thio-SL plus NADPH effected the complete degradation of the P-450(17 alpha,lyase). Neither progesterone nor SL caused P-450 destruction with the reconstituted enzyme preparation. The results provide direct evidence for the activation of 7 alpha-thio-SL by the 17 alpha-hydroxylase and support the hypothesis that a mechanism-based inhibition of the enzyme occurs. The data also provide additional evidence that 7 alpha-thio-SL is an obligatory intermediate in the degradation of P-450 by SL. PMID- 1875915 TI - Solubilization and characterization of a high affinity ivermectin binding site from Caenorhabditis elegans. AB - Ivermectin is a member of the avermectin family of compounds that are used to treat helminth and arthropod diseases in humans, domestic animals, and plants. A membrane-bound high affinity ivermectin binding site was extracted from Caenorhabditis elegans with the nonionic detergent 1-O-n-octyl-beta-D glucopyranoside. The free-living nematode C. elegans is highly sensitive to the avermectins and was used as a model of parasitic nematodes. The membrane-bound and detergent-solubilized ivermectin binding sites are stable and exhibit high affinity binding, with dissociation constants of 0.11 nM and 0.20 nM, respectively. The maximum binding of [3H]ivermectin is 0.54 pmol/mg of membrane protein and 0.66 pmol/mg of detergent-soluble protein. Kinetic analysis of ivermectin binding shows that the ivermectin binding sites form a slowly reversible complex with ivermectin. The rates of dissociation of [3H]ivermectin with the solubilized and membrane-bound binding sites are 0.005 min-1 and 0.006 min-1, respectively. The association rate of the soluble binding site is 0.053 nM 1 min-1, slightly slower than that observed for the membrane-bound site, 0.074 nM 1 min-1. To characterize the ivermectin binding site, competition experiments were performed by inhibiting [3H]ivermectin binding with several avermectin derivatives and the neurotransmitter gamma-aminobutyric acid (GABA). The order of potency was 22,23-dihydroavermectin B1a monosaccharide greater than 22,23 dihydroavermectin B1a aglycone greater than 3,4,8,9,10,11,22,23-octahydro B1 avermectin for both the membrane-bound and NOG-soluble binding sites. GABA did not compete with ivermectin binding, although it has been suggested that ivermectin acts at the GABA-gated chloride channel in some invertebrate systems. Optimum ivermectin binding and assay conditions have been determined. The detergent-soluble ivermectin binding site appears to be negatively charged and has a pl of 4.0 and an apparent Mr in Triton X-100 micelles of 340,000. Detergent solubilization of a high affinity ivermectin binding site will enable the subsequent purification and characterization of a putative site of ivermectin action. PMID- 1875916 TI - Rapid and sensitive gas-chromatographic determination of caffeine in blood plasma, saliva, and xanthine beverages. AB - A gas chromatographic procedure is reported for the determination of caffeine in plasma, saliva, and xanthine beverages. Using a 75 cm column packed with OV-17, nitrogen-sensitive detection, and 1 ml samples, a suitable limit of analysis (coefficient of variation (CV) = 10.2%) of 50 ng/ml was obtained in plasma. Within-day CVs at caffeine concentrations of 0.1-0.5-2.0-7.5-15.0 micrograms/ml in plasma were 7.7-5.6-4.8-3.8-3.4%, respectively. The limit of detection, defined as the injected quantity of caffeine giving rise to a signal to noise ratio of 2, is 40 pg, corresponding to a plasma concentration of 1 ng/ml. The procedure involves addition of the internal standard 7-pentyl theophylline and alkaline extraction of the sample with dichloromethane. The method described rivals any gaschromatographic assay published so far in rapidness and accuracy. Plasma and saliva caffeine concentrations were determined in a healthy male volunteer after swallowing 400 ml of coffee. The calculated pharmacokinetic parameters, assuming complete absorption of caffeine from the G.I. tract, agree well with previously published values. PMID- 1875918 TI - Isolation and partial characterization of a protein kinase NII from wheat germ chromatin. AB - A protein kinase, type NII, has been purified from wheat germ chromatin. The enzyme, which uses both ATP and GTP as phosphoryl donors, catalyzes the phosphorylation of casein, phosvitin and E. coli RNA polymerase, but not of histone proteins. Polypeptide bands at 46 kDa, 37 kDa and 25 kDa were estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autophosphorylation of the 25 kDa subunit was observed following incubation of the purified kinase with (gamma-32P)ATP and (gamma-32P)GTP. PMID- 1875917 TI - A proposed role for IF-3 and EF-T in maintaining the specificity of prokaryotic initiation complex formation. AB - Initiation factor-free 30S subunits of E. coli ribosomes bind aminoacyl-tRNAs more efficiently than fMet-tRNA(fMet). Elongator-tRNA binding was unaffected by IF-1 or IF-2 but was inhibited by IF-3. Their combination reduced this binding up to 40% and stimulated that of fMet-tRNA(fMet). Unexpectedly, EF-T also prevented elongator-tRNA binding by complexing both to the 30S and to the aminoacyl-tRNAs. Using AUGU3 as mRNA, elongator-tRNAs competed with fMet-fRNA(fMet) and with tRNA(fMet), fMet-tRNA(fMet) reacted with puromycin after addition of 50S subunits suggesting that it occupied the P site. EF-T directed binding of phe-tRNA to the 30S.AUGU3 complex at the A site only if fMet-tRNA(fMet) or tRNA(fMet) filled the P/E site. We propose that one function of EF-T may be to prevent the entry of aminoacyl-tRNAs into the 30S particle during initiation. The possibility that a special site for fMet-tRNA resides on 16S rRNA is also discussed. PMID- 1875919 TI - Activated ribosomal RNA synthesis in regenerated rat liver upon inhibition of protein synthesis. AB - Cycloheximide (Cyh), administered at a dose of 5 mg/kg body wt blocks protein synthesis in normal rat liver (NRL) and regenerating rat liver (RRL). The rate of synthesis of 45S pre-rRNA in RRL, studied after RNA labelling in vivo is activated 2.8 times. Pre-r RNA synthesis in RRL is more sensitive to the stopped translation, but never falls down to the level in NRL. The major contribution to the rDNA transcription activation in RRL comes from the 20-fold increase in the number of pol I molecules engaged in the transcription, the elongation rate being 1.4-fold accelerated. Cyh quenches partially the enhanced rDNA transcription in RRL: the number of pol I molecules and their elongation rate are about 1.7-fold and 1.5-fold higher, respectively, than the corresponding values in NRL after Cyh treatment. The results show that two different mechanisms control the number and the rate of initiation and elongation of RNA polymerase I in rat liver; one of them depends on continuous protein synthesis and can be inactivated by Cyh, the other is Cyh resistant. PMID- 1875920 TI - DNA sequence specific interactions of histone H1. AB - Histone H1 is know to play a role in the formation and maintenance of higher order chromatin structure. It has been recently suggested that the linker histone might be also involved in the regulation of the activity of individual genes. If H1 is a regulatory factor in eukaryotic gene transcription, it should possess specificity of binding to defined DNA sequences. This review is an attempt to summarize and discuss the existing literature data on DNA sequence-specific interactions of histone H1. PMID- 1875921 TI - Small acidic peptides are bound to E. coli DNA. AB - Low molecular weight peptides have been isolated by alkali extraction from deproteinized DNA of E. coli cells grown in the presence of radioactive glutamic acid or orthophosphate. The labeled peptides, purified by gel filtration chromatography on Sephadex G25 and G10, contain prevailingly glutamic acid, aspartic acid, glycine, serine and alanine. Electrophoretic studies at different pH show that some peptide fractions contain a phosphoric residue. The N-terminus of the phosphorylated peptides is apparently blocked and they were able to bind to DNA in the presence of Mg2+ ions. Moreover the acidic peptides extracted from E. coli DNA show a sharp activity in the control of lambda phage DNA transcription 'in vitro'. PMID- 1875922 TI - Inhibition of translation of transforming growth factor-beta 3 mRNA by its 5' untranslated region. AB - We have cloned and sequenced the 5' untranslated region of the transforming growth factor-beta 3 (TGF-beta 3) mRNA as well as the adjacent genomic sequence. S1 nuclease analysis identified a single transcription start site. We have thus determined that the 5' untranslated region is about 1.1 kb long and contains 11 open reading frames. In vitro translation of the TGF-beta 3 precursor coding sequence was markedly inhibited by the presence of the 5' untranslated region. Similarly, when the 5' untranslated region of TGF-beta 3 was introduced upstream of the coding sequence of chloramphenicol acetyltransferase, in vitro translation was inhibited. Furthermore, upon transfection into 293 cells, chloramphenicol acetyltransferase expression was inhibited by the 5' untranslated region of TGF beta 3. The degree of translational inhibition was inversely proportional to the amount of transfected DNA. Mutation analysis implicated multiple segments of the 5' untranslated region as contributing to the inhibitory effect. Deletion of much of the 5'-most 640 nucleotides, including 8 of the 11 upstream ATGs, relieved much but not all of the inhibitory influence of the 5' untranslated region of TGF beta 3 mRNA. The two upstream open reading frames closest to the initiator codon for the TGF-beta 3 coding sequence also decreased translational efficiency, since mutation of either ATG resulted in increased translation. Transfection results with T47-D cells, a cell line which expresses TGF-beta 3 mRNA, were similar to those obtained with the 293 cell line. Thus, TGF-beta 3 mRNA is a recent example of an expanding group of growth-related mRNAs in which the 5' untranslated region contains upstream open reading frames and other sequences which inhibit translation. PMID- 1875923 TI - Derepression of mouse beta-major-globin gene transcription during erythroid differentiation. AB - Functional analysis of the mouse beta-major-globin gene promoter has revealed a negative regulatory element (-100 to -250 bp) which represses promoter activity in mouse erythroleukemia (MEL) cells. Promoter activity is induced 14-fold during terminal differentiation of MEL cells. Three major in vitro binding sites for NF1 (-250 bp), GATA-1 (-212 bp), and a sequence at -165 bp (BB1) have been defined in this region. Site-directed mutagenesis of any one of the three sites resulted in a five- to sixfold up-regulation of promoter activity in uninduced MEL cells, but only three- to fourfold stimulation was observed from the mutant promoters during MEL cell terminal differentiation. This finding suggests that all three sites are required for repressor activity in uninduced MEL cells and that derepression occurs during MEL cell differentiation. BB1 DNA-binding activity decreases during MEL cell differentiation, suggesting a central role for this factor in modulating the effects of the repressor element. The BB1-binding factor also competes with the CCAAT-binding protein for binding the CCAAT motif. The fact that a reduced but significant stimulation of promoter activity during differentiation is observed in the absence of the repressor element raises the possibility that the BB1 factor also down-regulates transcription in undifferentiated MEL cells by displacing binding of CCAAT-binding protein to the proximal CCAAT motif. PMID- 1875924 TI - Determination of Candida tropicalis acyl coenzyme A oxidase isozyme function by sequential gene disruption. AB - A recently developed transformation system has been used to facilitate the sequential disruption of the Candida tropicalis chromosomal POX4 and POX5 genes, encoding distinct isozymes of the acyl coenzyme A (acyl-CoA) oxidase which catalyzes the first reaction in the beta-oxidation pathway. The URA3-based transformation system was repeatedly regenerated by restoring the uracil requirement to transformed strains, either through selection for spontaneous mutations or by directed deletion within the URA 3 coding sequence, to permit sequential gene disruptions within a single strain of C. tropicalis. These gene disruptions revealed the diploid nature of this alkane- and fatty acid-utilizing yeast by showing that it contains two copies of each gene. A comparison of mutants in which both POX4 or both POX5 genes were disrupted revealed that the two isozymes were differentially regulated and displayed unique substrate profiles and kinetic properties. POX4 was constitutively expressed during growth on glucose and was strongly induced by either dodecane or methyl laurate and to a greater extent than POX5, which was induced primarily by dodecane. The POX4 encoded isozyme demonstrated a broad substrate spectrum in comparison with the narrow-spectrum, long-chain oxidase encoded by POX5. The absence of detectable acyl-CoA oxidase activity in the strain in which all POX4 and POX5 genes had been disrupted confirmed that all functional acyl-CoA oxidase genes had been inactivated. This strain cannot utilize alkanes or fatty acids for growth, indicating that the beta-oxidation pathway has been functionally blocked. PMID- 1875925 TI - Expression of the murine alpha B-crystallin gene in lens and skeletal muscle: identification of a muscle-preferred enhancer. AB - The alpha B-crystallin gene is expressed at high levels in lens and at lower levels in some other tissues, notably skeletal and cardiac muscle, kidney, lung, and brain. A promoter fragment of the murine alpha B-crystallin gene extending from positions -661 to +44 and linked to the bacterial chloramphenicol acetyltransferase (CAT) gene showed preferential expression in lens and skeletal muscle in transgenic mice. Transfection experiments revealed that a region between positions -426 and -257 is absolutely required for expression in C2C12 and G8 myotubes, while sequences downstream from position -115 appear to be determinants for lens expression. In association with a heterologous promoter, a 427 to -259 fragment functions as a strong enhancer in C2C12 myotubes and less efficiently in myoblasts and lens. Gel shift and methylation interference studies demonstrated that nuclear proteins from C2C12 myoblasts and myotubes specifically bind to the enhancer. PMID- 1875926 TI - In situ distinction between steroid receptor binding and transactivation at a target gene. AB - We have developed a DNA interference assay in the yeast Saccharomyces cerevisiae that is designed to indicate the intracellular DNA-binding status of the estrogen receptor. The assay utilizes a promoter containing multiple copies of a GAL4 estrogen receptor binding sequence. This element is designed so that either an estrogen receptor or a GAL4 molecule, but not both, can occupy it simultaneously. The assay is extremely sensitive, and at concentrations of estrogen receptor below that required for maximal transcriptional activation of its target estrogen response element, a quantitative inhibition of GAL4-mediated transcription is seen. Inhibition occurs thought the disruption of complex cooperative interactions among the GAL4 molecules in this reporter. The data obtained from our experiments show that at low concentrations of receptor, hormone is required to promote DNA binding. Overexpression of receptor leads to occupation of the estrogen receptor element in the absence of ligand. In contrast, this latter receptor form will not activate transcription. Our results are consistent with a two-step process for receptor activation. Ligand first causes dissociation of receptor from an inhibitory complex within the cell and produces a DNA-binding form. Second, it converts receptor to a transcriptionally competent form. With use of this yeast model system, these two steps can be distinguished in situ. PMID- 1875928 TI - Double-strand gap repair in a mammalian gene targeting reaction. AB - To better understand the mechanism of homologous recombination in mammalian cells that facilitates gene targeting, we have analyzed the recombination reaction that inserts a plasmid into a homologous chromosomal locus in mouse embryonic stem cells. A partially deleted HPRT gene was targeted with various plasmids capable of correcting the mutation at this locus, and HPRT+ recombinants were directly selected in HAT medium. The structures of the recombinant loci were then determined by genomic Southern blot hybridizations. We demonstrate that plasmid gaps of 200, 600, and 2,500 bp are efficiently repaired during the integrative recombination reaction. Targeting plasmids that carry a double-strand break or gap in the region of DNA homologous to the target locus produce 33- to 140-fold more hypoxanthine-aminopterin-thymidine-resistant recombinants than did these same plasmids introduced in their uncut (supercoiled) forms. Our data suggest that double-strand gaps and breaks may be enlarged prior to the repair reaction since sequence heterologies carried by the incoming plasmids located close to them are often lost. These results extend the known similarities between mammalian and yeast recombination mechanisms and suggest several features of the insertional (O-type) gene targeting reaction that should be considered when one is designing mammalian gene targeting experiments. PMID- 1875927 TI - Two isoforms of murine hck, generated by utilization of alternative translational initiation codons, exhibit different patterns of subcellular localization. AB - Mammalian hck, a member of the src family of tyrosine kinases, is expressed predominantly in cells of the myeloid and B-lymphoid lineages. Using mutational analysis, we have investigated the molecular basis of two immunoreactive forms of murine hck of 56 and 59 kDa found in numerous hemopoietic cell types. Our results indicate that translation of murine p59hck initiates from a CTG codon located 21 codons 5' of an ATG that is utilized to generate p56hck. We provide evidence that two human hck isoforms are generated by the same mechanism. Subcellular fractionation studies reveal that while p59hck and p56hck are associated with membranes of various murine B-lymphoid and myeloid cell lines, p59hck alone is also located in the cytosol. In contrast to membrane-associated p59hck, which is metabolically labeled with [3H]myristic acid and exhibits amphiphilic properties in Triton X-114 detergent, cytosolic p59hck is hydrophilic, suggesting that it is not acylated. Possible mechanisms are proposed to account for these observations. PMID- 1875929 TI - High expression of a 3'----5' exonuclease activity is specific to B lymphocytes. AB - V(D)J joining, the immunoglobulin heavy-chain (IgH) class switch, and somatic hypermutation directed at variable regions are unique genetic recombination or mutation events which occur during B-cell differentiation. The enzymatic process directing and controlling these events remains obscure. An assay for exonucleolytic activity has been devised, and an exonuclease activity expressed at high levels in normal B lymphocytes has been detected. The high expression of this enzyme is specific to B lymphocytes and may be developmentally regulated. We have partially purified a B-cell-associated nuclease by column chromatography. Using this preparation, we have begun a rigorous analysis of its activity. This activity is a nonprocessive, 3'----5' exonuclease with a requirement for divalent cations. Our studies demonstrate that EDTA, poly(dI-dC), and glycerol are all inhibitory to B-cell-associated exonucleolytic activity. The exonuclease displays sequence preference but no sequence specificity when tested on a variety of native DNA substrates. This nuclease is distinct from other exonuclease activities previously described. PMID- 1875931 TI - Repair of a synthetic abasic site involves concerted reactions of DNA synthesis followed by excision and ligation. AB - A synthetic analog of an abasic site in DNA is efficiently repaired by a short patch repair mechanism in soluble extracts of Xenopus laevis oocytes (Y. Matsumoto and D. F. Bogenhagen, Mol. Cell. Biol. 9:3750-3757, 1989). We present a detailed analysis of the repair mechanism, using extracts depleted of endogenous nucleotide pools. ATP was required for repair with a sharp optimal concentration of 5 mM. The initial rate of repair was increased by preincubation of the DNA in the extract in the presence of ATP. During this preincubation, the DNA was cleaved on the 5' side of the lesion by a class II apurinic-apyrimidinic endonuclease, but removal of the abasic sugar residue was not observed prior to addition of deoxynucleotides to the reaction. Immediately following DNA synthesis, excision and ligation proceeded in a coordinated manner to complete repair. DNA preincubated in the extract in the absence of deoxynucleotides remained associated with repair enzymes during gel filtration. These observations suggest that the enzymes involved in concerted repair of the abasic site form a complex on DNA. PMID- 1875930 TI - The extracellular matrix coordinately modulates liver transcription factors and hepatocyte morphology. AB - The extracellular matrix (ECM) promotes tissue morphogenesis, cell migration, and the differentiation of a variety of cell types. However, the mechanisms by which ECM causes differentiated gene expression have been unknown. In this report, we show that culturing the hepatocyte-derived cell line H2.35 on an ECM gel changes cell morphology and selectively stimulates the transcription of a subset of liver specific genes, including serum albumin. Transcriptional activation by ECM also occurs with transfected plasmids bearing the transcriptional enhancer of the albumin gene. ECM substrates of different composition activated the albumin enhancer only when the ECM promoted a cuboidal, differentiated cell morphology. Enhancer activation by the ECM was mediated by two liver transcription factors, HNF3 alpha and eH-TF, which appear to be regulated differently by matrix. Specifically, we found that a collagen gel substratum caused a selective increase in the factor HNF3 alpha at the levels of mRNA accumulation and DNA-binding activity in nuclear extracts, both in H2.35 cells and in the hepatoma cell line HepG2. We conclude that the ECM can stimulate cell differentiation by selectively activating transcriptional regulatory factors and that such regulation occurs coordinately with ECM-promoted changes in cell shape. PMID- 1875932 TI - Differential regulation of glucose transporter isoforms by the src oncogene in chicken embryo fibroblasts. AB - The increase in glucose transport that occurs when chicken embryo fibroblasts (CEFs) are transformed by src is associated with an increase in the amount of type 1 glucose transporter protein, and we have previously shown that this effect is due to a decrease in the degradation rate of this protein. The rate of CEF type 1 glucose transporter biosynthesis and the level of its mRNA are unaffected by src transformation. To study the molecular basis of this phenomenon, we have been isolating chicken glucose transporter cDNAs by hybridization to a rat type 1 glucose transporter probe at low stringency. Surprisingly, these clones corresponded to a message encoding a protein which has most sequence similarity to the human type 3 glucose transporter and which we refer to as CEF-GT3. CEF-GT3 is clearly distinct from the CEF type 1 transporter that we have previously described. Northern (RNA) analysis of CEF RNA with CEF-GT3 cDNA revealed two messages of 1.7 and 3.3 kb which were both greatly induced by src transformation. When the CEF-GT3 cDNA was expressed in rat fibroblasts, a three-to fourfold enhancement of 2-deoxyglucose uptake was observed, indicating that CEF-GT3 is a functional glucose transporter. Northern analyses using a CEF-GT3 and a rat type 1 probe demonstrated that there is no hybridization between different isoforms but that there is cross-species hybridization between the rat type 1 probe and the chicken homolog. Southern blot analyses confirmed that the chicken genomic type 1 and type 3 transporters are encoded by distinct genes. We conclude that CEFs express two types of transporter, type 1 (which we have previously reported to be regulated posttranslationally by src) and a novel type 3 isoform which, unlike type 1, shows mRNA induction upon src transformation. We conclude that src regulates glucose transport in CEFs simultaneously by two different mechanisms. PMID- 1875933 TI - Phorbol esters selectively and reversibly inhibit a subset of myofibrillar genes responsible for the ongoing differentiation program of chick skeletal myotubes. AB - Phorbol esters selectively and reversibly disassemble the contractile apparatus of cultured skeletal muscle as well as inhibit the synthesis of many contractile proteins without inhibiting that of housekeeping proteins. We now demonstrate that phorbol esters reversibly decrease the mRNA levels of at least six myofibrillar genes: myosin heavy chain, myosin light chain 1/3, myosin light chain 2, cardiac and skeletal alpha-actin, and skeletal troponin T. The steady state message levels decrease 50- to 100-fold after 48 h of exposure to phorbol esters. These decreases can be attributed at least in part to decreases in transcription rates. For at least two genes, cardiac and skeletal alpha-actin, some of the decreases are the result of increased mRNA turnover. In contrast, the cardiac troponin T steady-state message level does not change, and its transcription rate decreases only transiently upon exposure to phorbol esters. Phorbol esters do not decrease the expression of the housekeeping genes, alpha tubulin, beta-actin, and gamma-actin. Phorbol esters do not decrease the steady state message levels of MyoD1, a gene known to be important in the activation of many skeletal muscle-specific genes. Cycloheximide blocks the phorbol ester induced decreases in transcription, message stability, and the resulting steady state message level but does not block the tetradecanoyl phorbol acetate-induced rapid disassembly of the I-Z-I complexes. These results suggests a common mechanism for the regulation of many myofibrillar genes independent of MyoD1 mRNA levels, independent of housekeeping genes, but dependent on protein synthesis. PMID- 1875935 TI - Synapsis, strand scission, and strand exchange induced by the FLP recombinase: analysis with half-FRT sites. AB - We have used a previously described cross-linking assay and half-FRT site substrates to examine the requirements for synapsis, strand exchange, and strand scission. The cross-linking assay showed that the minimum functional FRT site needed for synapsis contains two inverted FLP-binding elements surrounding an 8 bp core. This indicates that four FLP molecules interact with four binding elements in a synaptic complex. The analysis using half-sites showed that the enzyme can catalyze efficient strand exchange between a half-site and the intact FRT site. The reaction occurred only if the half-site had at least 2 bp but no more than 4 bp of the adjoining core sequence. The exchange occurred exclusively at the regions of limited core homology between the respective half-site and the FRT site. The absence of strand exchange between an intact site and a half-site bearing regions of core nonhomology indicates that 1 bp of homology is not sufficient for the formation of stable recombinant structures. Qian et al. (X.-H. Qian, R. B. Inman, and M. M. Cox, J. Biol. Chem. 265:21779-21788, 1990) have recently shown that the FLP protein can catalyze the formation of dimeric, trimeric, and tetrameric complexes with half-FRT sites. We show that only half sites that contained at least 2 bp of adjacent core could form stable dimer products and be cleaved by the enzyme. Stable dimers were formed between a noncleavable half-site and a cleavable half-site, suggesting that only a single cleavage event is needed for the formation of the dimer. PMID- 1875934 TI - Glucocorticoid regulation of transforming growth factor beta 1 activity and binding in osteoblast-enriched cultures from fetal rat bone. AB - Transforming growth factor beta (TGF-beta) enhances replication and bone matrix protein synthesis and associates with distinct binding sites in osteoblast enriched cultures from fetal rat bone. In the organism high levels of or sustained exposure to glucocorticoids alters bone cell activity and decreases bone mass, effects that may be mediated in part by changes in local TGF-beta actions in skeletal tissue. Preexposure of osteoblast-enriched cultures to 100 nM cortisol reduced the stimulatory effects of TGF-beta 1 on DNA and collagen synthesis by 40 to 50%. Binding studies showed that cortisol moderately enhanced total TGF-beta 1 binding, but chemical cross-linking and polyacrylamide gel electrophoretic analysis revealed an increase only within Mr 250,000 (type III) TGF-beta-binding complexes, which are thought to represent extracellular TGF-beta storage sites. In contrast, a decrease in TGF-beta 1 binding was detected in Mr 65,000 (type I) and 85,000 (type II) complexes, which have been implicated as signal-transducing TGF-beta receptors. Our present studies therefore indicate that glucocorticoids can decrease the anabolic effects of TGF-beta 1 in bone, and these may occur in part by a redistribution of its binding toward extracellular matrix storage sites. Alterations of this sort could contribute to bone loss associated with glucocorticoid excess. PMID- 1875936 TI - Target frequency and integration pattern for insertion and replacement vectors in embryonic stem cells. AB - Gene targeting has been used to direct mutations into specific chromosomal loci in murine embryonic stem (ES) cells. The altered locus can be studied in vivo with chimeras and, if the mutated cells contribute to the germ line, in their offspring. Although homologous recombination is the basis for the widely used gene targeting techniques, to date, the mechanism of homologous recombination between a vector and the chromosomal target in mammalian cells is essentially unknown. Here we look at the nature of gene targeting in ES cells by comparing an insertion vector with replacement vectors that target hprt. We found that the insertion vector targeted up to ninefold more frequently than a replacement vector with the same length of homologous sequence. We also observed that the majority of clones targeted with replacement vectors did not recombine as predicted. Analysis of the recombinant structures showed that the external heterologous sequences were often incorporated into the target locus. This observation can be explained by either single reciprocal recombination (vector insertion) of a recircularized vector or double reciprocal recombination/gene conversion (gene replacement) of a vector concatemer. Thus, single reciprocal recombination of an insertion vector occurs 92-fold more frequently than double reciprocal recombination of a replacement vector with crossover junctions on both the long and short arms. PMID- 1875937 TI - The serum response factor is extensively modified by phosphorylation following its synthesis in serum-stimulated fibroblasts. AB - Growth factor regulation of c-fos proto-oncogene transcription is mediated by a 20-bp region of dyad symmetry, termed the serum response element. The inner core of this element binds a 67-kDa phosphoprotein, the serum response factor (SRF), that is thought to play a pivotal role in the c-fos transcriptional response. To investigate the mechanism by which SRF regulates c-fos expression, we generated polyclonal anti-SRF antibodies and used these antibodies to analyze the biochemical properties of SRF. These studies indicate that the synthesis of SRF is transient, occurring within 30 min to 4 h after serum stimulation of quiescent fibroblasts. Newly synthesized SRF is transported to the nucleus, where it is increasingly modified by phosphorylation during progression through the cell cycle. Within 2 h of serum stimulation, differentially modified forms of SRF can be distinguished on the basis of the ability to bind a synthetic serum response element. SRF protein exhibits a half-life of greater than 12 h and is predominantly nuclear, with no change occurring in its localization upon serum stimulation. We find that the induction of SRF synthesis is regulated at the transcriptional level and that cytoplasmic SRF mRNA is transiently expressed with somewhat delayed kinetics compared with c-fos mRNA expression. These features of SRF expression suggest a model whereby newly synthesized SRF functions in the shutoff of c-fos transcription. PMID- 1875938 TI - Transcriptional activation in an improved whole-cell extract from Saccharomyces cerevisiae. AB - We report an improved in vitro transcription system for Saccharomyces cerevisiae. Small changes in assay and whole-cell extraction procedures increase selective initiation by RNA polymerase II up to 60-fold over previous conditions (M. Woontner and J. A. Jaehning, J. Biol. Chem. 265:8979-8982, 1990), to levels comparable to those obtained with nuclear extracts. We have found that the simultaneous use of distinguishable templates with and without an upstream activation sequence is critical to the measurement of apparent activation. Transcription from any template was very sensitive to the concentrations of template and nontemplate DNA, extract, and activator (GAL4/VP16). Alterations in reaction conditions led to proportionately greater changes from a template lacking an upstream activation sequence; thus, the apparent ratio of activation is largely dependent on the level of basal transcription. Using optimal conditions for activation, we have also demonstrated activation by a bona fide yeast activator, heat shock transcription factor. PMID- 1875939 TI - Differential ability of proximal and remote element pairs to cooperate in activating RNA polymerase II transcription. AB - To investigate the synergism or cooperative interaction between transcription elements, we have designed and constructed a series of synthetic polymerase II promoters with different combinations of elements. These include three different CCAAT boxes, which correspond to the binding sites for CP1, CP2, and NFI, a GC box, a CACCC box, and an ATF/CREB-binding site. The synthetic promoters containing these elements in proximal positions were linked to a test gene (CAT). Tandem repeats of AP1- and AP2-binding sites, the simian virus 40 enhancer, and DNA-binding sites for GAL-estrogen receptor were cloned downstream of the test gene. The strength of these promoters was then tested in transient-expression assays in HeLa TK- cells. In the context of the adenovirus major late promoter TATA box, the promoters containing only certain combinations of elements are active in this assay. Some elements appear to cooperate nearly universally, but others exhibit strong selectivity. These results indicate strongly selective synergistic interactions between elements and suggest that levels of promoter strength may be determined by the extent of compatibility between factors bound to proximal and enhancer sites. PMID- 1875940 TI - Telomerase is processive. AB - Telomerase synthesizes tandem repeats of the sequence d(TTGGGG) onto input d(TTGGGG)n primer oligonucleotides (C. W. Greider and E. H. Blackburn, Cell 43:405-413). An intrinsic RNA component of the enzyme provides the template for d(TTGGGG)n repeat synthesis [C. W. Greider and E. H. Blackburn, Nature (London) 337:331-337, 1989; G.-L. Lu, J. D. Bradley, L. D. Attardi, and E. H. Blackburn, Nature (London) 344:126-132, 1990]. In a typical reaction, products greater than 2,000 nucleotides were synthesized in 60 min. Dilution and primer challenge experiments showed that these long products were synthesized processively. The apparent processivity was not due to a higher affinity of the enzyme for long d(TTGGGG) products over the shorter competitors. The degree of processivity was quantitated; telomerase synthesized approximately 520 nucleotides before half of the enzyme had dissociated. After dissociating, telomerase reinitiated d(TTGGGG)n synthesis on new primer oligonucleotides. The products from a telomerase reaction have a characteristic 6-nucleotide banding pattern (C. W. Greider and E. H. Blackburn, Cell 51:887-898, 1987). A strong pause in the reaction occurs after the addition of the first G in the sequence d(TTGGGG). Both the processivity and the banding pattern analysis imply that in the elongation mechanism there must be a translocation step after the 9 nucleotides of internal template RNA have been copied to the extreme 5' end. PMID- 1875941 TI - Identification of a specific exon sequence that is a major determinant in the selection between a natural and a cryptic 5' splice site. AB - The first intron of the early region 3 from adenovirus type 2 contains a cryptic 5' splice site, Dcr1, 74 nucleotides downstream from the natural site D1. The cryptic site can be activated when the natural site is inactivated by mutagenesis. To investigate the basis for selection between a natural and a cryptic 5' splice site, we searched for cis-acting elements responsible for the exclusive selection of the natural site. We show that both the relative intrinsic strength of the sites and the sequence context affect the selection. A 120 nucleotide segment located at the 3' end of exon 1 enhances splicing at the proximal site D1; in its absence the two sites are used according to their strength. Thus, three cis-acting elements are involved in the silencing of the cryptic site: the sequence of D1, the sequence of Dcr1, and an upstream exonic sequence. We show that the exonic element folds, in solution, into a 113 nucleotide-long stem-loop structure. We propose that this potential stem-loop structure which is located 6 nucleotides upstream of the exon 1-intron junction is responsible for the preferential use of the natural 5' splice site. PMID- 1875942 TI - Interactions between adenylate cyclase and the yeast GTPase-activating protein IRA1. AB - The adenylate cyclase system of the yeast Saccharomyces cerevisiae contains many proteins, including the CYR1 polypeptide, which is responsible for catalyzing the formation of cyclic AMP from ATP, RAS1 and RAS2 polypeptides, which mediate stimulation of cyclic AMP synthesis by guanine nucleotides, and the yeast GTPase activating protein analog IRA1. We have previously reported that adenylate cyclase is only peripherally bound to the yeast membrane. We have concluded that IRA1 is a strong candidate for a protein involved in anchoring adenylate cyclase to the membrane. We base this conclusion on the following criteria: (i) a disruption of the IRA1 gene produced a mutant with very low membrane-associated levels of adenylate cyclase activity, (ii) membranes made from these mutants were incapable of binding adenylate cyclase in vitro, (iii) IRA1 antibodies inhibit binding of adenylate cyclase to the membrane, and (iv) IRA1 and adenylate cyclase comigrate on Sepharose 4B. PMID- 1875943 TI - trans activation of nerve growth factor in transgenic mice containing the human T cell lymphotropic virus type I tax gene. AB - Three lines of transgenic mice containing the human T-cell lymphotropic virus type I (HTLV-I) tax gene develop neurofibromas composed of perineural fibroblasts (S. H. Hinrichs, M. Nerenberg, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1340-1343, 1987; M. Nerenberg, S. H. Hinrichs, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1324-1327, 1987). Tumors and tumor cell lines derived from these mice produce neurite outgrowth from PC-12 cells and nerve growth factor (NGF), as determined by RNA (Northern) blot analysis and enzyme-linked immunosorbent assays. In vitro cotransfection studies demonstrate that Tax is able to trans activate the NGF promoter in NIH 3T3 fibroblast cells. The major cis-acting tax-responsive element in the NGF promoter (AGGGTGTGACGA) has 92% homology with a tax-responsive element contained within the 21-bp repeats of the HTLV-I long terminal repeat. The receptor for NGF is also expressed in the transgenic tumor cells, suggesting that Tax may activate an autocrine mechanism through the upregulation of NGF. PMID- 1875944 TI - elt-1, an embryonically expressed Caenorhabditis elegans gene homologous to the GATA transcription factor family. AB - The short, asymmetrical DNA sequence to which the vertebrate GATA family of transcription factors binds is present in some Caenorhabditis elegans gene regulatory regions: it is required for activation of the vitellogenin genes and is also found just 5' of the TATA boxes of tra-2 and the msp genes. In vertebrates GATA-1 is specific to erythroid lineages, whereas GATA-2 and GATA-3 are present in multiple tissues. In an effort to identify the trans-acting factors that may recognize this sequence element in C. elegans, we used a degenerate oligonucleotide to clone a C. elegans homolog to this gene. We call this gene elt-1 (erythrocytelike transcription factor). It is single copy and specifies a 1.75-kb mRNA that is present predominantly, if not exclusively, in embryos. The region of elt-1 encoding two zinc fingers is remarkably similar to the DNA-binding domain of the vertebrate GATA-binding proteins. However, outside of the DNA-binding domains the amino acid sequences are quite divergent. Nevertheless, introns are located at identical or nearly identical positions in elt-1 and the mouse GATA-1 gene. In addition, elt-1 mRNA is trans-spliced to the 22-base untranslated leader, SL1. The DNA upstream of the elt-1 TATA box contains eight copies of the GATA recognition sequence within the first 300 bp, suggesting that elt-1 may be autogenously regulated. Our results suggest that the specialized role of GATA-1 in erythroid gene expression was derived after separation of the nematodes and the line that led to the vertebrates, since C. elegans lacks an erythroid lineage. PMID- 1875945 TI - Inducibility of the DNA repair gene encoding O6-methylguanine-DNA methyltransferase in mammalian cells by DNA-damaging treatments. AB - The inducibility of the mammalian O6-methylguanine-DNA methyltransferase (MGMT) gene encoding the MGMT protein (EC 2.1.1.63) responsible for removal of the procarcinogenic and promutagenic lesion O6-alkylguanine from DNA was examined by an analysis of transcription of the MGMT gene following exposure of repair competent (Mex+) and repair-deficient (Mex-) cells to N-methyl-N'-nitro-N nitrosoguanidine (MNNG). While human and rodent Mex- cells (CHO-9, V79, HeLa MR) showed no detectable MGMT mRNA despite the presence of the gene in their genome, the amount of it in several Mex+ lines (NIH 3T3, HeLa S3, HepG2) paralleled their MGMT activity. However, none of these cell lines showed an increase in the MGMT mRNA level after treatment with various concentrations of MNNG. In contrast, MNNG treated rat hepatoma cells, H4IIE and FTO-2B, both Mex+, had three- to fivefold more MGMT mRNA than the corresponding untreated controls as measured 12 to 72 h after alkylation. N-Methyl-N-nitrosourea, methyl methanesulfonate, N-hydroxyethyl N-chloroethylnitrosourea, UV light, and X rays caused a similar accumulation of MGMT mRNA in rat hepatoma cells. Studies with inhibitors of RNA and protein synthesis indicate that the induced increase in the amount of MGMT mRNA was due to enhanced transcription of the gene. Furthermore, they revealed the turnover of the MGMT mRNA to be relatively low (half-life, greater than 7 h). Mutagen-induced increase of transcription of MGMT mRNA in H4IIE cells was accompanied by elevation of MGMT repair activity and resulted in reduction of mutation frequency after a challenge dose of MNNG. Although induction of MGMT mRNA transcription has been observed in two rodent hepatoma cell lines so far, this appears to be the first demonstration of inducibility of a mammalian gene encoding a clearly define DNA repair function. The transcription activation of the MGMT gene protects cells from the mutagenic effects of methylating agents. PMID- 1875946 TI - Characterization of the major regulatory element upstream of the human alpha globin gene cluster. AB - The major positive regulatory activity of the human alpha-globin gene complex has been localized to an element associated with a strong erythroid-specific DNase I hypersensitive site (HS -40) located 40 kb upstream of the zeta 2-globin mRNA cap site. Footprint and gel shift analyses of the element have demonstrated the presence of four binding sites for the nuclear factor GATA-1 and two sites corresponding to the AP-1 consensus binding sequence. This region resembles one of the major elements of the beta-globin locus control region in its constitution and characteristics; this together with evidence from expression studies suggests that HS -40 is a primary element controlling alpha-globin gene expression. PMID- 1875947 TI - 5'-flanking sequences mediate butyrate stimulation of embryonic globin gene expression in adult erythroid cells. AB - A stable transfection assay was used to test the mechanism by which embryonic globin gene transcription is stimulated in adult erythroid cells exposed to butyric acid and its analogs. To test the appropriate expression and inducibility of chicken globin genes in murine erythroleukemia (MEL) cells, an adult chicken beta-globin gene construct was stably transfected. The chicken beta-globin gene was found to be coregulated with the endogenous adult mouse alpha-globin gene following induction of erythroid differentiation of the transfected MEL cells by incubation with either 2% dimethyl sulfoxide (DMSO) or 1 mM sodium butyrate (NaB). In contrast, a stably transfected embryonic chicken beta-type globin gene, rho, was downregulated during DMSO-induced MEL cell differentiation. However, incubation with NaB, which induces MEL cell differentiation, or alpha-amino butyrate, which does not induce differentiation of MEL cells, resulted in markedly increased levels of transcription from the stably transfected rho gene. Analysis of histone modification showed that induction of rho gene expression was not correlated with increased bulk histone acetylation. A region of 5'-flanking sequence extending from -569 to -725 bp upstream of the rho gene cap site was found to be required for both downregulation of rho gene expression during DMSO induced differentiation and upregulation by treatment with NaB or alpha-amino butyrate. These data are support for a novel mechanism by which butyrate compounds can alter cellular gene expression through specific DNA sequences. The results reported here are also evidence that 5'-flanking sequences are involved in the suppression of embryonic globin gene expression in terminally differentiated adult erythroid cells. PMID- 1875948 TI - Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene. AB - Two forms of activated BCR/ABL proteins, P210 and P185, that differ in BCR derived sequences, are associated with Philadelphia chromosome-positive leukemias. One of these diseases is chronic myelogenous leukemia, an indolent disease arising in hematopoietic stem cells that is almost always associated with the P210 form of BCR/ABL. Acute lymphocytic leukemia, a more aggressive malignancy, can be associated with both forms of BCR/ABL. While it is virtually certain that BCR/ABL plays a central role in both of these diseases, the features that determine the association of a particular form with a given disease have not been elucidated. We have used the bone marrow reconstitution leukemogenesis model to test the hypothesis that BCR sequences influence the ability of activated ABL to transform different types of hematopoietic cells. Our studies reveal that both P185 and P210 induce a similar spectrum of hematological diseases, including granulocytic, myelomonocytic, and lymphocytic leukemias. Despite the similarity of the disease patterns, animals given P185-infected marrow developed a more aggressive disease after a shorter latent period than those given P210-infected marrow. These data demonstrate that the structure of the BCR/ABL oncoprotein does not affect the type of disease induced by each form of the oncogene but does control the potency of the oncogenic signal. PMID- 1875949 TI - Tissue factor mRNA in THP-1 monocytic cells is regulated at both transcriptional and posttranscriptional levels in response to lipopolysaccharide. AB - Tissue factor (TF) is transiently expressed in human monocytes exposed to the inflammatory agonist bacterial lipopolysaccharide (LPS). Since TF is the major cellular initiator of the coagulation protease cascades, it is inferred that its expression within the vasculature is strictly regulated. In this study, we investigated mechanisms which control TF mRNA expression in the human monocytic cell line THP-1. LPS induced a rapid and transient accumulation of the mature 2.2 kb TF mRNA, which was maximal at 2 h. After stimulation, the rate of transcription of the TF gene was increased (3.3 +/- 1.3)fold. In addition, we observed a significant change in TF mRNA stability: at 1 h after LPS stimulation, TF mRNA was stable during a 60-min period and had a half-life of greater than 120 min, whereas at 2 h, the half-life had declined to 25 +/- 5 min. Furthermore, a larger (3.4-kb) TF RNA species was induced in these cells; the size of this species and data from selective hybridizations with intron-specific probes are consistent with the presence of an unspliced copy of intron 1. These results demonstrate that the LPS-induced accumulation of TF mRNA levels in these monocytic cells is accomplished by both transcriptional and posttranscriptional control mechanisms. PMID- 1875950 TI - Induction of neurite outgrowth by v-src mimics critical aspects of nerve growth factor-induced differentiation. AB - PC12 cells treated with nerve growth factor (NGF) or infected with Rous sarcoma virus differentiate into sympathetic, neuronlike cells. To compare the differentiation programs induced by NGF and v-src, we have established a PC12 cell line expressing a temperature-sensitive v-src protein. The v-src-expressing PC12 cell line was shown to elaborate neuritic processes in a temperature inducible manner, indicating that the differentiation process was dependent on the activity of the v-src protein. Further characterization of this cell line, in comparison with NGF-treated PC12 cells, indicated that the events associated with neurite outgrowth induced by these two agents shared features but could be distinguished by others. Both NGF- and v-src-induced neurite outgrowths were reversible. In addition, NGF and v-src could prime PC12 cells for NGF-induced neurite outgrowth, and representative early and late NGF-responsive genes were also induced by v-src. However, unlike NGF-induced neurite growth, v-src-induced neurite outgrowth was not blocked at high cell density. A comparison of phosphotyrosine containing-protein profiles showed that v-src and NGF each increase tyrosine phosphorylation of multiple cellular proteins. There was overlap in substrates; however, both NGF-specific and v-src-specific tyrosine phosphorylations were observed. One protein which was found to be phosphorylated in both the NGF- and v-src-induced PC12 cells was phospholipase C-gamma 1. Taken together, these results suggest that v-src's ability to function as an inducing agent may be a consequence of its ability to mimic critical aspects of the NGF differentiation program and raise the possibility that Src-like tyrosine kinases are involved in mediating some of the events triggered by NGF. PMID- 1875952 TI - Inhibitors of membrane lipid metabolism enhance complement-mediated nucleated cell killing through distinct mechanisms. AB - The ability of nucleated cells to survive limited complement attack has been attributed to metabolic processes unique to these cells, such as rapid elimination of terminal complement complexes (TCC) from their surfaces. The biochemical processes activated by complement channels responsible for cell defense remain poorly defined. Metabolic inhibitors affecting membrane lipid turnover have been shown to increase the complement-mediated cell death. Whether these metabolic inhibitors increase lytic susceptibility of target cells by reducing the rate of TCC elimination has not been previously evaluated. In the present study, inhibitors of membrane lipid transmethylation and lysolecithin reacylation were evaluated in view of the observations that TCC concurrently increase lipid transmethylation and inhibit lysolecithin reacylation, and the inhibition of lipid transmethylation correlates with increased complement mediated cell death. We have measured the formation as well as the elimination of C5b-9 on the target membrane that affect the outcome of cell death. Our results in the present communication indicated that inhibitors of transmethylation and lysolecithin reacylation increased TCC-mediated cell death through distinct pathways, the former by allowing more efficient deposition of TCC, and the latter by impairing TCC elimination. PMID- 1875951 TI - Multiple CArG boxes in the human cardiac actin gene promoter required for expression in embryonic cardiac muscle cells developing in vitro from embryonal carcinoma cells. AB - Chimeric genes composed of the human cardiac actin promoter driving the Escherichia coli lacZ reporter gene were constructed, transfected, and stably integrated into genomes of P19 embryonal carcinoma cells. The transfected constructs were expressed actively in cardiac myocytes formed following dimethyl sulfoxide (DMSO)-induced cell differentiation but poorly in undifferentiated cultures and in cultures treated with retinoic acid to develop into derivatives of the neuroectoderm. A number of deletions of the promoter were constructed and tested. Three regions required for efficient expression in P19-derived cardiac muscle were identified, each containing sequences referred to as CArG boxes (CC[AT-rich]6GG). This analysis indicated that regulatory sequences important for expression in cardiac muscle were present upstream of the core promoter identified previously by transient assays in skeletal myoblasts. Expression of the cardiac actin promoter was enhanced 10-fold in undifferentiated P19 cells in the presence of the myoD protein. The promoter regions important for expression in P19-derived cardiocytes were similar to those important for myoD-induced enhancement, a result we interpret to be consistent with the idea that cardiac muscle might contain a myoD-like activity. PMID- 1875953 TI - Interaction of the envelope glycoprotein of human immunodeficiency virus with C1q and fibronectin under conditions present in human saliva. AB - Human saliva has been shown to reduce the infectivity of human immunodeficiency virus (HIV) particles in vitro. The factors in human saliva involved in this inhibition of HIV infectivity are unknown, although the salivary sediment of normal individuals has the major HIV neutralizing activity. Interestingly, the first complement component (C1) has been detected on the surface of the salivary sediment in the whole saliva of normal individuals. At the relatively low ionic strength of saliva, we determined that purified human C1q bound with high affinity to the envelope glycoprotein of HIV. Normally, the interaction of the C1q globular heads with immune complexes causes C1 activation. However, direct interactions between C1 and rgp120 (or rgp160) did not lead to C1 fixation, as determined by hemolytic studies with rate-limiting levels of C1, nor did rgp120 cause C1 activation as determined by activated C1s-mediated C4 conversion in normal human serum. Using ELISA, it was observed that intact C1, with the C1r2C1s2 tetramer associated with the collagen-like stem of C1q, did not bind to immobilized rgp120, whereas free C1q did bind. In addition, digestion of the C1q stem portion with collagenase completely eliminated its binding to rgp120. These findings suggest that the collagen-like stem region of C1q, rather than the globular heads, may participate in the binding to the envelope glycoprotein of HIV. Fibronectin, which is present in submandibular saliva, appeared to bind to rgp120 and to enhance the interaction of C1q with rgp120. It is conceivable that C1q and fibronectin, in binding and sequestering HIV particles (i.e. to the salivary sediment), may play an important role in the reduction of HIV transmission via saliva. Further studies will be needed to test the latter speculation. PMID- 1875955 TI - Toward the conquest of pain. PMID- 1875954 TI - The Fab/c fragment of IgG produced by cleavage at cyanocysteine residues. AB - The intra- and inter-heavy chain disulfides of rabbit IgG were cleaved by mild reduction with either dithiothreitol or sulfite and cyanocysteines generated by treatment with either 2-nitro-5-thiocyanobenzoic acid or KCN, respectively. When cleavage occurs at a cyanocysteine residue in the hinge region of one heavy chain alone the Fab/c fragment is produced. Fab/c was also produced by papain digestion of IgG. Fab/c made by papain digestion was able to active complement in haemolytic assays; this activity was lost after cleavage of its accessible disulfide bonds. Fab/c made by cyanylysis of sulfite-reduced IgG was also active in these assays, but Fab/c made by cyanylysis of dithiothreitol-reduced IgG was not. Treatment of the latter fragment with cysteine and cystine resulted in partial reformation of cleaved disulfide bonds. Fab/c was also made from human IgG and from murine IgG2a and IgG2b. PMID- 1875956 TI - History of pain concepts and pain therapy. AB - The development of the concept of pain and its treatment constitutes one of the most interesting and fascinating chapters in the history of medicine. The concept proposed by Aristotle and other ancient Greek philosophers that pain was a passion of the soul remained widely accepted for some 22 centuries, and treatment remained empirical and often ineffective. For a century after the scientific study of pain began, several theories were proposed, and these theories prompted the development of various therapeutic modalities. However, until two decades ago, pain research remained conceptually stagnant; the meager work done was not commensurate with the magnitude and clinical importance of pain. Consequently, pain treatment remained somewhat empirical and ineffective. Whatever knowledge and effective therapeutic modalities were available were not properly applied, primarily because medical students and physicians were not taught the basic principles of pain management. Fortunately, during the past two decades, significant advances have been made in our knowledge of basic mechanisms and a variety of new modalities have been introduced and old ones refined. Although we should be proud of these advances, much more needs to be done if the millions of patients with acute and chronic pain are to be managed effectively. This requires sustaining and expanding research programs; educating and training health professionals; and informing the public. PMID- 1875957 TI - Psychological aspects of pain. AB - Psychological factors have a major role in the development and maintenance of pain. Further research to clarify the nature of the relationship between these factors and pain is required. When evaluating patients with acute or chronic pain, attention must be given to psychological factors. PMID- 1875958 TI - The difference between acute and chronic pain. AB - Acute and chronic pain are different clinical entities. Acute pain is provoked by a specific disease or injury, serves a useful biologic purpose, is associated with skeletal muscle spasm and sympathetic nervous system activation, and is self limited. Chronic pain, in contrast, may be considered a disease state. It is pain that outlasts the normal time of healing, if associated with a disease or injury. Chronic pain may arise from psychological states, serves no biologic purpose, and has no recognizable end-point. Both acute and chronic pain are an enormous problem in the United States, costing 650 million lost workdays and $65 billion a year. The therapy of acute pain is aimed at treating the underlying cause and interrupting the nociceptive signals. The therapy of chronic pain must rely on a multidisciplinary approach and should involve more than one therapeutic modality. PMID- 1875959 TI - Nonnarcotic analgesics and tricyclic antidepressants for the treatment of chronic nonmalignant pain. AB - Chronic nonmalignant pain is often characterized by multiple treatment failures, a pattern of maladaptive behavior, and depression. Often there is a history of inappropriate and excessive use of medications for pain. Prior and ongoing use of narcotics and sedatives acts to compound and aggravate the chronic pain syndrome. A first step in treatment is controlled withdrawal of these agents. Nonnarcotic analgesics, NSAIDs, and tricyclic antidepressants are commonly employed in patients with chronic pain. Effective use of these agents requires understanding of their pharmacokinetic and pharmacodynamic properties. Use of a fixed-time schedule is necessary to achieve an effective, sustained therapeutic response. Careful patient education and monitoring for side effects and toxicity are necessary, particularly in the elderly and patients with coexisting medical disorders. Incidence of side effects and toxicity may be reduced by choice of drug and modification of dosing regimen. Nonnarcotic analgesics, TCAs, and NSAIDs are seldom effective by themselves in resolving the pain and distress of patients with chronic nonmalignant pain. This is particularly true when maladaptive behavior coexists. A comprehensive multimodal pain management program encompassing additional pain-relieving strategies and behavior-modifying techniques should be considered and utilized in conjunction with medication. PMID- 1875960 TI - Temporomandibular disorders and facial pain. PMID- 1875961 TI - Diagnosis and treatment of myofascial pain. AB - The importance of muscle as a source of pain should not be underestimated. Proper diagnosis of the four types of muscle pain (tension, spasm, muscle deficiency, and trigger points) is essential to effective management. Pain-diagnostic instruments can quantify tenderness and spasm and help evaluate treatment results. PMID- 1875962 TI - Update on postoperative pain management. PMID- 1875963 TI - Postoperative pain management in children. AB - Postoperative pain management in children is a topic that has been neglected in the past but is currently an active field of interest and effort. Clearly, the child's cognitive understanding of and emotional response to pain are different than an adult's, and these differences make pain assessment and control more difficult. Ongoing work to develop more accurate techniques of estimating pain intensity in children may have helpful results. The effects of untreated pain in children are similar to those in adults but may have more long-term consequences in children. In the past, postoperative pain treatment in children was often inadequate, but newer techniques, such as continuous infusion of opioids, patient controlled analgesia, epidural administration of opioids, and regional analgesia, hold promise for improved care in the future. PMID- 1875964 TI - Acute herpetic and postherpetic neuralgia: clinical features and management. AB - Herpes zoster is a prevalent disorder that is transitory in most patients. Postherpetic neuralgia is defined by the persistence of pain following herpes zoster for some arbitrarily defined period, such as two months. Although most patients with postherpetic neuralgia experience a gradual remission of the pain, symptoms are prolonged in many, and intractable pain occurs in a few. This review describes the clinical characteristics and management of these syndromes. PMID- 1875965 TI - Organization of a multidisciplinary pain center. AB - Chronic pain is a complex, multifaceted experience that leads not only to disability and dysfunction but also to suffering and unrealized human potential. To be effective, a pain management center must be multidisciplinary in concept as well as practice. It must employ practitioners whose assessments are not restricted to specialty interests. They must communicate effectively with other specialists and cooperate to design and implement the best treatment program for each patient. The ultimate goal is rehabilitation of the patient to a more functional life despite residual pain. This may involve breaking the doctor shopping cycle for those patients seeking cure, detoxification to more appropriate medications, addressing personal and family conflicts through counseling, assisting the patient in resolving socioeconomic problems, and, ultimately, teaching the patient to function more effectively within the bounds of any physical limitations. PMID- 1875966 TI - Paracentesis with intravenous infusion of albumin as compared with peritoneovenous shunting in cirrhosis with refractory ascites. AB - BACKGROUND: There is no satisfactory treatment for refractory ascites in patients with cirrhosis. Both peritoneovenous shunts and paracentesis have been used, but there is uncertainty about their relative merits. METHODS: We studied 89 patients with cirrhosis and refractory ascites who were randomly assigned to receive either repeated large-volume paracentesis plus intravenous albumin or a LeVeen peritoneovenous shunt. Patients in the paracentesis group in whom recurrent tense ascites developed during follow-up were treated with paracentesis, and those in the peritoneovenous-shunt group with diuretic agents or by the insertion of a new shunt if there was shunt obstruction. RESULTS: During the first hospitalization, ascites was removed in all 41 patients in the paracentesis group and in 44 of the 48 patients in the peritoneovenous-shunt group. The mean (+/- SD) duration of hospitalization in the two groups was 11 +/- 5 and 19 +/- 9 days, respectively (P less than 0.01). There were no significant differences in the number of patients who had complications or died. During follow-up, 37 patients in each group were hospitalized again. In the paracentesis group, the number of rehospitalizations for any reason (174 vs. 97 in the peritoneovenous-shunt group) or for ascites (125 vs. 38) was significantly higher, and the median time to a first readmission for any reason (1 +/- 1 vs. 2 +/- 2 months) or for ascites (2 +/- 2 vs. 8 +/- 17 months) was significantly shorter than in the peritoneovenous-shunt group. The total times in the hospital during follow-up, however, were similar in the two groups (48 +/- 49 and 44 +/- 39 days, respectively). Three patients had obstructions of their peritoneovenous shunts during their first hospitalizations, and 15 patients had a total of 20 obstructions during follow-up. Survival was similar in both groups. CONCLUSIONS: The LeVeen shunt and paracentesis are equally effective in relieving refractory ascites. The former may provide better long-term control of ascites, but shunt occlusion is common and survival is not improved. PMID- 1875967 TI - Advanced glycosylation end products in patients with diabetic nephropathy. AB - BACKGROUND: Glucose reacts nonenzymatically with proteins in vivo, chemically forming covalently attached glucose-addition products and cross-links between proteins. The excessive accumulation of rearranged late-glucose-addition products, or advanced glycosylation end products (AGEs), is believed to contribute to the chronic complications of diabetes mellitus. METHODS: To elucidate the relation of AGEs to diabetic complications, we used a radioreceptor assay to measure serum and tissue AGEs in diabetic (Types I and Type II) and nondiabetic patients with different levels of renal function. Serum AGEs were measured as a low-molecular-weight (less than or equal to 10 kd) peptide fraction and a high-molecular-weight (greater than 10 kd) protein fraction. RESULTS: The mean (+/- SD) AGE content of samples of arterial-wall collagen from 9 diabetic patients was significantly higher than that of samples from 18 nondiabetic patients (14.5 +/- 5.2 vs. 3.6 +/- 1.5 AGE units per milligram, P less than 0.001). Moreover, diabetic patients with end-stage renal disease had almost twice as much AGE in tissue as diabetic patients without renal disease (21.3 +/- 2.8 vs. 11.5 +/- 1.9 AGE units per milligram, P less than 0.001). The AGE levels in both serum fractions were elevated in the patients with diabetes, and the levels of AGE peptides correlated directly with serum creatinine (P less than 0.001) and inversely with creatinine clearance (P less than 0.005), suggesting that levels of AGE peptides increased with the severity of diabetic nephropathy. In six patients with diabetes who required hemodialysis, the levels of AGE peptides were five times higher than in eight normal subjects (82.8 +/- 9.4 vs. 15.6 +/- 3.4 AGE units per milliliter, P less than 0.001). In another group of diabetic patients the mean serum creatinine level, which decreased by 75 percent during a session of hemodialysis, whereas the level of AGE peptides decreased by only 24 percent. Serum levels of AGE peptides were normal in two patients with normal serum creatinine levels after renal transplantation. CONCLUSIONS: AGEs accumulate at a faster-than-normal rate in arteries and the circulation of patients with diabetes; the increase in circulating AGE peptides parallels the severity of renal functional impairment in diabetic nephropathy. PMID- 1875968 TI - Relation between skin cancer and HLA antigens in renal-transplant recipients. AB - BACKGROUND: Recipients of renal allografts are at an increased risk for skin cancer. It is also known that recipients who are homozygous for HLA antigens are at an increased risk for certain cancers, as are those who are mismatched with their donors for these antigens. In a case-control study we assessed the relation between skin cancer in renal-transplant recipients and HLA homozygosity and mismatching. METHODS: Of 764 patients who received renal transplants between 1966 and 1988, 66 had squamous-cell carcinoma or basal-cell carcinoma of the skin after transplantation. HLA homozygosity was assessed in all 66 recipients, and HLA mismatching in 39; the results were compared with those in 124 recipients without skin cancer. We also investigated the relation between skin cancer and the use of immunosuppressive drugs. In separate case-control analyses we investigated the influence of exposure to the sun and keratotic skin lesions on the risk of skin cancer. RESULTS: The risk of squamous-cell carcinoma was increased in recipients mismatched for HLA-B antigens; the relative risks were 2.6 (95 percent confidence interval, 1.1 to 6.5) and 5.0 (95 percent confidence interval, 1.3 to 19.0) with mismatching for one and two antigens, respectively, as compared with no mismatching. Mismatching for HLA-A or HLA-DR antigens had no effect on the risk of squamous-cell carcinoma, and there was no association between mismatches at any of the HLA loci and the occurrence of basal-cell carcinoma. The total doses of azathioprine and prednisone were not associated with the occurrence of skin cancer or with HLA matching. Exposure to sunlight and keratotic skin lesions were strongly associated with skin cancer but not with HLA mismatching. Homozygosity for HLA-DR was more frequent among the patients with squamous-cell carcinoma (relative risk, 2.5; 95 percent confidence interval, 0.95 to 4.6) and among patients with 100 or more keratotic skin lesions (relative risk, 4.8; 95 percent confidence interval, 1.5 to 15.1). CONCLUSIONS: HLA-B mismatching is significantly associated with the risk of squamous-cell carcinoma in renal-transplant recipients, as is HLA-DR homozygosity. An indirect effect on the level of immunosuppression does not appear to explain these findings, nor does exposure to sunlight or the number of keratotic skin lesions account for this observation. PMID- 1875969 TI - Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease. AB - BACKGROUND: The treadmill exercise test identifies patients with different degrees of risk of death from cardiovascular events. We devised a prognostic score, based on the results of treadmill exercise testing, that accurately predicts outcome among inpatients referred for cardiac catheterization. This study was designed to determine whether this score could also accurately predict prognosis in unselected outpatients. METHODS: We prospectively studied 613 consecutive outpatients with suspected coronary disease who were referred for exercise testing between 1983 and 1985. Follow-up was 98 percent complete at four years. The treadmill score was calculated as follows: duration of exercise in minutes--(5 x the maximal ST-segment deviation during or after exercise, in millimeters)--(4 x the treadmill angina index). The numerical treadmill angina index was 0 for no angina, 1 for nonlimiting angina, and 2 for exercise-limiting angina. Treadmill scores ranged from -25 (indicating the highest risk) to +15 (indicating the lowest risk). RESULTS: Predicted outcomes for the outpatients, based on their treadmill scores, agreed closely with the observed outcomes. The score accurately separated patients who subsequently died from those who lived for four years (area under the receiver-operating-characteristic curve = 0.849). The treadmill score was a better discriminator than the clinical data and was even more useful for outpatients than it had been for inpatients. Approximately two thirds of the outpatients had treadmill scores indicating low risk (greater than or equal to +5), reflecting longer exercise times and little or no ST segment deviation, and their four-year survival rate was 99 percent (average annual mortality rate, 0.25 percent). Four percent of the outpatients had scores indicating high risk (less than -10), reflecting shorter exercise times and more severe ST-segment deviation; their four-year survival rate was 79 percent (average annual mortality rate, 5 percent). CONCLUSIONS: The treadmill score is a useful and valid tool that can help clinicians determine prognosis and decide whether to refer outpatients with suspected coronary disease for cardiac catheterization. In this study, it was a better predictor of outcome than the clinical assessment. PMID- 1875970 TI - Shattuck Lecture--the health care industry: where is it taking us? PMID- 1875971 TI - Allergic rhinitis. PMID- 1875972 TI - Transient monocular blindness caused by vasospasm. PMID- 1875973 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 38-1991. A 33-year-old man with dilatation of the ascending aorta and aortic regurgitation. PMID- 1875974 TI - Toward a basic understanding of diabetic complications. PMID- 1875975 TI - Immunogenetic factors in skin cancer. PMID- 1875976 TI - Prognostic applications of exercise testing. PMID- 1875977 TI - Risk of transmission of HIV from surgeon to patient. PMID- 1875978 TI - Serotonin and coronary artery disease. PMID- 1875979 TI - Detection of inhaled pentamidine in health care workers. PMID- 1875980 TI - Myasthenia gravis unmasked by cocaine abuse. PMID- 1875981 TI - Pseudoanuria due to superabsorbent diapers. PMID- 1875982 TI - The health care proxy and the living will. PMID- 1875983 TI - Prevalence of dermatophytes and yeasts (Candida spp., Malassezia furfur) in HIV patients. A study of former drug addicts. AB - The prevalence of dermatophytes and yeasts (Candida spp. and Pityrosporum spp.) was studied in 40 former drug-addicts, all of whom were HIV seropositive but otherwise had no other symptoms (2nd Stage CDC Atlanta, 1987). We considered 7 skin areas for dermatophytes and Pityrosporum spp. (scalp, forehead, nose, back, chest, groin, toe webs) and the mouth for yeasts. Dermatophytes were found in 8 (20%) and tinea pedis was the most common dermatophytosis: Tricophyton rubrum was the fungus most frequently isolated (6 cases or 15%). The HIV+ group showed almost the same rate of dermatophytes colonisation compared to a group of 121 athletes and to the control group. Candida spp. was present in 27 cases (67.5%) but clinical oral lesions were evident only in 5 patients (12.5%). Statistically significant differences were found in the presence of Candida spp. in HIV patients and controls (p less than 0.05). The lipophilic yeast Pityrosporum ovale was evaluated with quantitative and qualitative methods. Quantitative variations were evident between HIV patients and controls. P. ovale was present in 10 cases: 3 (7.5%) of them showed dischromic lesions while in 7 cases (17.5%) no clinical symptoms were evident. PMID- 1875984 TI - A survey of dermatophytes from human patients in the United States from 1985 to 1987. AB - A survey of dermatophytes isolated from patients seeking medical advice was made from 1985 to 1987 in the United States. The survey included 54 locations with data from 45 cities and one state. Listing of the isolated dermatophytes and the frequency given by percentage of the total follows: Trichophyton rubrum 54.8%, T. tonsurans 31.3%, T. mentagrophytes 6.0%, Microsporum canis 4.0%, Epidermophyton floccosum 2.0%, M. gypseum 0.6%, and T. verrucosum 0.2%. Out of a total of 14,696 isolates M. audouinii was cultured 13 times, T. violaceum 12 times, M. nanum 6 times, T. terrestre 4 times, and T. soudanense twice. Single isolations were made of M. fulvum, M. ferrugineum and T. schoenleinii. Collection of dermatophyte data in Tucson, Arizona, began in 1966. In 1987, the first case of tinea capitis caused by T. tonsurans was observed. Other isolates of this organism as the cause of tinea capitis were made in this city during that year. These infections were in black children. With the recent growth of Tucson, the percentage of blacks in the population increased and this pathogen was introduced into the general population. PMID- 1875985 TI - Potential pathogenicity of Cladosporium tennuisimum, Phaeoisaria clematidis and Ramichloridium subulatum in a mouse model. AB - The potential pathogenicity of one isolate each of Cladosporium tennuisimum, Phaeoisaria clematidis and Ramichloridium subulatum for mice was investigated by intravenous, intraperitoneal and subcutaneous routes of inoculation with saline and mucin suspensions of the organisms. No mice died during the experimental period. Dark nodular lesions were formed in the liver, spleen, kidneys, intestine, stomach, omentum and diaphragm after inoculation through the intravenous and intraperitoneal routes. Gross lesions were produced in the lungs of one mouse inoculated intravenously with R. subulatum. Localised nodular lesions were formed in the subcutis following the subcutaneous route. Tissue response was characterised by granulomatous inflammatory reaction. Fungal elements were confined within the granulomata. Though the fungi showed limited pathogenic potential, they may represent a hazard under conditions of compromised host immunity. PMID- 1875986 TI - Virulence and pathogenicity of human and environmental isolates of Cladosporium carrionii in new born ddY mice. AB - Three strains of Cladosporium carrionii, two human isolates and one from a xerophilous plant, were used to study the effect of culture conditions in 106 newborn ddY mice. Growth in a complex medium (YPG) and a basal synthetic medium (BSM) was compared. Filamentous forms developed during static incubation while conidia were readily formed with shaking. Mice inoculated intraperitoneally were sacrificed and autopsied after 4 weeks. Mortality was related only to sporulated exponential phase growing cells. Invasiveness ability was preserved in all experimental conditions. BSM medium that inhibited exopigment formation appeared more suitable than YPG to obtain intact cells for further studies. Biochemical and physiological alteration associated with shape changes during differentiation of vegetative cells into spores could play an important role in virulence of C. carrionii. PMID- 1875987 TI - Deficiency in the incorporation of labeled thymidine and inhibition in the biosynthesis of interleukin-2 in lymphocytes obtained from Histoplasma capsulatum infected mice. AB - The incorporation of (3H) thymidine and the biosynthesis of interleukin-2(IL-2) were investigated in Concanavalin A (ConA) and histoplasmin stimulated lymphocytes from spleen of infected Balb/c mice with the yeast phases of Histoplasma capsulatum. The ability to incorporate (3H) thymidine of Con A stimulated lymphocytes in culture from spleen of Histoplasma capsulatum infected mice, as well as the IL-2 content present in the supernatants of that cultures, were depressed along the first three weeks of the experiments, but starting week five, normal values were restored or even discretly increased. Incorporation of (3H) thymidine in histoplasmin stimulated lymphocytes remained inhibited along the seven weeks the experiment lasted. Results showed that inoculation of H. capsulatum yeast in mice provoked a temporary immunosuppression on cell mediated immunity, that can be explained by means of the inability of T cells to produce enough IL-2 necessary for the proliferation of T cells in culture. PMID- 1875989 TI - Problems of drug dependence 1990. Proceedings of the 52nd annual meeting. The Committee on Problems of Drug Dependence, Inc. Richmond, Virginia, June 1990. PMID- 1875988 TI - HLA antigens in Brazilian patients with paracoccidioidomycosis. AB - Eighty patients with paracoccidioidomycosis were typed for 43 HLA specificities from loci A, B, C and DR. A highly significant increased frequency of HLA-B40 (relative risk 29.2) and HLA-Cw1 (relative risk 8.8) were found in patients compared to control subjects. The frequencies HLA-A2, B7 and B21 were also increased in patients and haplotypes-B40-Cw1 and -A2-B40 were positively correlated with the disease. DR antigen frequencies were not significantly altered in the patients and evidence of a protective effect was not found for any of the 43 antigens tested. These findings further support the involvement of the HLA system in the genetic susceptibility to paracoccidioidomycosis and the importance of ethnic variability in this association. PMID- 1875990 TI - Prodynorphin gene expression in neuronal and endocrine cell types. PMID- 1875991 TI - Tissue-specific splicing of pro-enkephalin mRNA. AB - A testis cDNA library derived from 4-6 week-old rats was screened using a 32P labeled 435 base pair (bp) cDNA probe derived from exon 3 of rat brain proenkephalin (PE). Two positive clones were isolated from an initial screening of approximately 20,000 recombinant bacteriophage plaques. The longest insert (1,500 bp) was sequenced and was found to contain a portion of intron A at the 5' terminus. Intron B was sliced as it is in the brain, therefore, the domain structure of the cDNA was intron A-exon 2-exon 3, reading in the 5'-3' direction. Since the translational initiator codon is located at the 5'-terminus of exon 2, the reading frame of PE is unaltered, however, within intron A are 4 upstream AUG codons which exist in a favorable context for initiation of translation. It is probable that translation of PE would be inhibited by the presence of these upstream initiator codons, which may explain the discrepancy between the levels of PE mRNA and opioid peptides in the testis. Hypophysectomy prior to the onset of puberty was found to drastically reduce the level of PE mRNA in the testis and epididymus, suggesting that pituitary factors affect the expression of the PE gene in these tissues, either directly or indirectly. PMID- 1875992 TI - Synaptic regulation of the enkephalin gene and transcription factors in vivo: possible roles in drug abuse. PMID- 1875993 TI - In memoriam: Ulrich Weiss 1908-1989. PMID- 1875994 TI - Synthetic and biological studies of potential affinity ligands for the cannabinoid receptor based on CP-55, 244. PMID- 1875995 TI - Synthesis and receptor binding of cocaine analogs. PMID- 1875996 TI - Use of naltrexone for the diagnosis and treatment of reproductive hormone disorders in women. PMID- 1875997 TI - Neuroendocrine (HPA) and gastrointestinal effects of opiate antagonists: possible therapeutic application. PMID- 1875998 TI - Preclinical evaluation of the effects of buprenorphine, naltrexone and desipramine on cocaine self-administration. PMID- 1875999 TI - Buprenorphine treatment for concurrent heroin and cocaine dependence: phase I study. PMID- 1876000 TI - Intestinal contractions: excitatory actions of opioids. PMID- 1876001 TI - Assessing substance abuse and other psychiatric disorders: history of problems, state of affairs. PMID- 1876002 TI - The SCID: a clinical instrument for assessing psychiatric disorders. PMID- 1876003 TI - The CIDI and CIDI-substance abuse module (SAM): cross-cultural instruments for assessing DSM-III, DSM-III-R and ICD-10 criteria. PMID- 1876004 TI - Categorizing substance abusers using the ASI: implications for evaluation and treatment. PMID- 1876005 TI - Diagnosing personality disorders in substance abusers. PMID- 1876006 TI - Animal conflict, analgesia and the modulatory effects of FMRFamide-related peptides. PMID- 1876007 TI - FMRF-NH2-like peptides antiopiates. PMID- 1876008 TI - Illicit drug use during pregnancy: effects of opiates and cocaine on human placenta. PMID- 1876009 TI - Substance abuse patterns in pregnant women. PMID- 1876010 TI - Specificity of conditional responding to naturalistic stimuli in humans with different drug-use histories. PMID- 1876011 TI - A comparison of drug use and adjustment in urban adolescent children of substance abusers. PMID- 1876012 TI - College undergraduate drug use and life-styles, 1969, 1978 and 1989. AB - G SUBSTANCE ABUSE / * ep ENTS / * psychol INE HOL DRINKING / psychol BEHAVIOR PMID- 1876013 TI - Impulsivity and substance abusers: changes with treatment and recovery. PMID- 1876014 TI - Cathinone, a phenylpropylamine alkaolid from khat leaves that has amphetamine effects in humans. PMID- 1876015 TI - A substance abuse consultation service: characteristics of patients and pedagogical potential. PMID- 1876016 TI - Preliminary report on psychiatric comorbidity in adolescent substance abusers. PMID- 1876017 TI - Putative aminoalkylindoles (AAI) antagonists. PMID- 1876018 TI - Conformationally restrained aminoalkylindoles: potent, stereoselective ligands at the cannabinoid binding site. PMID- 1876019 TI - Cannabinoid-like effects of aminoalkylindole compounds on the physical properties of brain membranes: fluorescence polarization studies. PMID- 1876020 TI - Characterization of aminoalkylindole binding: selective displacement by cannabinoids. PMID- 1876021 TI - Marijuana use by methadone maintenance patients. PMID- 1876022 TI - Human avoidance responding with added point loss during acute tobacco abstinence. PMID- 1876023 TI - The role of nicotine titration in the smoking behavior. PMID- 1876024 TI - Smoking cessation, depression and dysphoria. PMID- 1876025 TI - Effect of repeated nicotine administration in nonsmokers. PMID- 1876026 TI - Smoking cessation for adolescent substance users: preliminary considerations. PMID- 1876027 TI - Behavioral and subjective effects of buspirone and lorazepam in sedative abusers: supra-therapeutic doses. PMID- 1876028 TI - Diazepam preference in males with and without a family history of alcoholism. PMID- 1876029 TI - Divided attention task performance in women with and without familial alcoholism. PMID- 1876030 TI - Human aggressive responding: effects of response-cost and ethanol. PMID- 1876031 TI - Reduced amplitudes of somatosensory evoked potentials observed after chronic ethanol exposure. PMID- 1876032 TI - Studies of the effect of nicotine on synaptosomal calcium accumulation using FURA 2. PMID- 1876033 TI - Synthesis and anticonvulsant activity of dextromethorphan analogs. PMID- 1876034 TI - Dextromethorphan inhibits but dextrorphan potentiates behavior induced by PCP and ketamine in rats. PMID- 1876035 TI - HIV infection in female intravenous drug abusers (IVDAs) of childbearing age in NYC drug clinics and their demographic profile. PMID- 1876036 TI - Factors associated with elevated risk of HIV among Hispanic IVDAs. PMID- 1876037 TI - HIV-risk behaviors among a middle class population: a preliminary investigation among adolescent vs. adult substance users. PMID- 1876038 TI - Chronic cocaine-induced supersensitivity id blocked by co-treatment with the peptide cyclo-(Leu-Gly). PMID- 1876039 TI - Genetic differences in the development of cocaine-kindled seizures. PMID- 1876040 TI - Lack of a genetic correlation between the convulsant and epileptogenic effects of cocaine and lidocaine. PMID- 1876041 TI - Day hospital versus inpatient cocaine dependence rehabilitation: an interim report. PMID- 1876042 TI - A treatment crisis: cocaine use by clients in methadone maintenance programs. PMID- 1876043 TI - Incidence of personality disorders in cocaine vs. alcohol-dependent females. PMID- 1876044 TI - Clinical features of cocaine induced paranoia. PMID- 1876045 TI - Liver function tests in non-parenteral cocaine users. PMID- 1876046 TI - Stereospecificity of mixed-action opioid agonist/antagonists in morphine-tolerant squirrel monkeys. PMID- 1876047 TI - The effect of prenatal methadone exposure of development and nociception during the early postnatal period of the rat. PMID- 1876048 TI - Involvement of spinal adenosine in descending antinociception produced by supraspinal receptor-selective opioid agonists. PMID- 1876049 TI - [D-Met2]-FMRFamide (DMFa): production of naloxone-sensitive antinociception in mouse tail-flick test. AB - Considerable data support the hypothesis that mammalian FMRFamide (Phe-Met-Arg Phe-NH2) or mammalian FMRFamide-related peptides (FaRPs) function as endogenous antiopiates (for review see Raffa, 1988). We report here that central administration (i.c.v.) of a FaRP with D-amino acid substitution in the second position, i.e. [D-Met2]-FMRFamide (DMFa), produces dose-related, naloxone reversible antinociception in the mouse tail-flick test. Hence, this modification appears to confer agonist-like activity. PMID- 1876050 TI - A computer-aided investigation into the role of hydrogen bonding in the binding conformation of the endo-ethenotetrahydrooripavine, PEO. PMID- 1876051 TI - Effects of opiate agonists and antagonists on cerebral metabolic activity in the conscious rat. PMID- 1876052 TI - Differential effects of calcitonin gene-related peptide in tests utilizing thermal versus nociceptive stimuli. PMID- 1876053 TI - Nonpeptide opioids: in vivo effects on the immune system. PMID- 1876054 TI - Distribution of opioid peptides in brain and GI tract: age- and species-specific differences. PMID- 1876055 TI - Modulation of NK activity: role of neuroendocrine status. PMID- 1876056 TI - Dependence-producing drug testing in opiate users in Warsaw, Poland. PMID- 1876057 TI - Metyrapone-induced withdrawal symptoms: symptoms in methadone-maintained patients. PMID- 1876058 TI - Cardiovascular components of the response to morphine. PMID- 1876059 TI - Factors influencing assessment of opioid miosis in humans. PMID- 1876060 TI - Spinal action of cannabinoid-induced antinociception. PMID- 1876061 TI - Aminoalkylindoles (AAIs): structurally novel cannabinoid-mimetics. PMID- 1876062 TI - Importance of reactive metabolites to the in vivo hepatic clearance of phencyclidine (PCP). PMID- 1876063 TI - Influence of phencyclidine (PCP) pharmacokinetics on PCP dependence after i.v. and s.c. routes of administration. PMID- 1876064 TI - Withdrawal from nicotine fails to produce a conditioned taste aversion to saccharine in rats and mice. PMID- 1876065 TI - The relationship between cocaine venous blood levels and the cardiovascular and subjective effects of smoked and intravenous cocaine. PMID- 1876066 TI - Low doses of caffeine can serve as reinforcers in humans. PMID- 1876067 TI - Assessment of mazindol for abuse liability. PMID- 1876068 TI - Low-dose caffeine discrimination in normal humans. PMID- 1876069 TI - Low-dose caffeine physical dependence in normal subjects: dose-related effects. PMID- 1876070 TI - The effects of deprivation on the reinforcing efficacy of smoking. PMID- 1876071 TI - Acute opioid physical dependence in humans: effects of varying the morphine morphine interval. PMID- 1876072 TI - Acute physical dependence in opiate-naive humans. PMID- 1876073 TI - Relative abuse liability and pharmacodynamics of transnasal and intramuscular butorphanol. PMID- 1876074 TI - Changes in mood, craving and sleep during acute abstinence reported by male cocaine addicts. PMID- 1876075 TI - Double blind assessment of buprenorphine withdrawal in opiate-addicts. PMID- 1876076 TI - Use and abuse of prescription and recreational drugs by chronic pain patients. PMID- 1876077 TI - Nicotine dependence in an urban population of young adults: prevalence and co morbidity with depression, anxiety and other substance dependencies. PMID- 1876078 TI - Drug use and abuse at historical black colleges. PMID- 1876079 TI - Drug use in women with bulimia and anorexia nervosa. PMID- 1876080 TI - Qat use in New York City. PMID- 1876081 TI - Patterns of drug abuse treatment utilization in a general population. PMID- 1876082 TI - Opening the "black box" of drug abuse treatment-measurement and evaluation of the treatment domain. PMID- 1876083 TI - Alerting drug abusers to overdose threats: the media's role. PMID- 1876084 TI - Metabolic studies of drugs of abuse. AB - Although still very preliminary, these studies exemplify how metabolic brain measurements can address questions of relevance in the investigation of drugs of addiction such as: 1. Mechanisms of drug toxicity, i.e., vascular pathology demonstrated from chronic use of cocaine. 2. Neurotransmitters that may be involved in the pharmacological actions of drugs, i.e., alcohol and the benzodiazepine-Gaba receptor complex, marijuana, and the cannabinoid receptor. 3. Mechanisms of drug withdrawal, i.e., hyperresponsivity of the brain to alcohol in the alcoholic, possibly as a consequence of increased sensitivity of the benzodiazepine-Gaba receptor complex. 4. Knowledge about brain function, i.e., the relation between activation of the cerebellum by marijuana and alcohol and the mood-changing effects of these drugs, suggests that the cerebellum may play a role in the mood disturbing actions seen with these drugs (a role which is different from the classical one which associates the cerebellum to motor regulation). Future work will provide more definitive answers to the above questions and will similarly provide information about mechanisms of toxicity, addiction, withdrawal, and reinforcement of other drugs of abuse. PMID- 1876085 TI - A historical perspective on British and American drug policies. PMID- 1876086 TI - Predictors of HIV seropositivity in Newark and Jersey City i.v. drug users not currently enrolled in treatment. PMID- 1876087 TI - Needle sharing behaviors associated with HIV among intravenous drug users (IVDUs): a two-year study. PMID- 1876088 TI - Ibogaine fails to reduce naloxone-precipitated withdrawal in the morphine dependent rat. PMID- 1876089 TI - HIV infection in intravenous drug abusers (IVDAs) in NYC drug treatment clinics: 1985-1989. PMID- 1876090 TI - The role of cocaine use in the HIV transmission among IVDUs: 1987 and 1988 cohort study. PMID- 1876091 TI - Effects of education on high risk HIV transmission behaviors. PMID- 1876092 TI - New York City's needle exchange experiment: policy implications from its first year. PMID- 1876093 TI - Diseases commonly found in the drug abuser: is there more than HIV? PMID- 1876094 TI - Intravenous drug abusers with antisocial personality disorder: high rate of HIV-1 infection. PMID- 1876095 TI - Psychiatric symptoms, high risk behaviors and HIV positivity among methadone patients. PMID- 1876096 TI - Preliminary results of polymerase chain reaction (PCR) testing of ELISA negative IVDUs in methadone treatment. PMID- 1876097 TI - Pre-treatment natural history of cocaine addiction. PMID- 1876098 TI - Behavioral and cardiovascular effects of cocaine and alcohol combinations in humans. PMID- 1876099 TI - Relapse to cocaine use following treatment: preliminary findings on the role of social support. PMID- 1876100 TI - Effects of bromocriptine on subjective and autonomic responses to cocaine associated stimuli. PMID- 1876101 TI - Effects of cocaine alone and in combination with bromocriptine in human cocaine abusers. PMID- 1876102 TI - Concurrent effects of acute intravenous cocaine in context of chronic desipramine in humans. PMID- 1876103 TI - Amantadine and desipramine in the treatment of cocaine abusing methadone maintained patients. PMID- 1876104 TI - Clinical trail of multiple treatment agents for cocaine dependence: a placebo control; elimination study. PMID- 1876105 TI - Mazindol treatment of cocaine abuse. A double-blind investigation. PMID- 1876106 TI - Fluoxetine for cocaine abuse in methadone patients: preliminary findings. PMID- 1876107 TI - In vitro d-amphetamine and cocaine increase opioid binding in mouse brain homogenate. PMID- 1876108 TI - Opiate-induced inhibition of calcium flux in immune cells. AB - Administration of morphine as a subcutaneous implant inhibits the initial influx of calcium (Ca2+) induced by mitogens in mouse splenocytes. This effect was not reproduced by incubation of splenocytes with morphine (10(-8)-10(-4)M). Within T cell subpopulations, CD4+, but not CD8+ cells were affected. Adrenalectomy abolished this effect of morphine in CD4+ but not B cells. Moreover, simultaneous administration of the opiate antagonist naltrexone blocked the effect of morphine in B cells, but not in CD4+ cells. These data indicate that inhibition of Ca2+ influx by morphine may be mediated through distinct glucocorticoid-dependent and independent mechanisms. The morphine-induced inhibition of Ca2+ influx in immune cells reported here may be an early event mediating opiate-induced immunosuppression. PMID- 1876109 TI - Acute effects of secobarbital and ethanol as a function of family alcoholism history. PMID- 1876110 TI - Neurofunctional consequences of in utero cocaine exposure. PMID- 1876111 TI - New trends in infant pain management: potential for opiate dependence. PMID- 1876112 TI - Cocaine, catecholamines and cardiac toxicity. PMID- 1876113 TI - Mapping the metabolic correlates of drug-induced euphoria. PMID- 1876114 TI - Effects of chronic cocaine on the behavioral and immunological effects of chronic stress in mice. PMID- 1876115 TI - Intrathecal morphine and insulin cause hypoglycemia in mice by different mechanisms. PMID- 1876116 TI - Immunosuppressive agent modulates the severity of opiate withdrawal. PMID- 1876117 TI - Opioid self-administration contingent on physiologic parameters. PMID- 1876118 TI - In vivo concentration-response relationships for fentanyl: absence of acute tolerance in the rat tail-flick test. PMID- 1876119 TI - Intraspinal opioids in frogs: a new behavioral model for the assessment of opioid action. PMID- 1876120 TI - Chronic tolerance to nicotine's effects on suppressing hunger and caloric intake. PMID- 1876121 TI - Acute marijuana smoking reduces vagal tone. PMID- 1876122 TI - Elevated drug saliva levels suggest a "depot-like" effect in subjects treated with sublingual buprenorphine. PMID- 1876123 TI - Interaction of cocaine with ethanol. PMID- 1876124 TI - Cocaethylene inhibits uptake of dopamine and can reach high plasma concentrations following combined cocaine and ethanol use. PMID- 1876125 TI - Acute tolerance to cocaine pressor effects in humans. PMID- 1876126 TI - Pharmacologic effects of methamphetamine vapor inhalation (smoking) in man. PMID- 1876127 TI - Plasma levels of methamphetamine after smoking of methamphetamine hydrochloride. PMID- 1876128 TI - Alcohol effects on HCG stimulated gonadal hormones in women. PMID- 1876129 TI - Medical methadone/interim report. PMID- 1876130 TI - Outpatient comparison of buprenorphine and methadone maintenance. I. Effects on opiate use and self-reported adverse effects and withdrawal symptomatology. PMID- 1876131 TI - Outpatient comparison of buprenorphine and methadone maintenance. II. Effects on cocaine usage, retention time in study and missed clinic visits. PMID- 1876132 TI - Methadone maintenance outcome as a function of detoxification fear: preliminary findings. PMID- 1876133 TI - Comparison of SCID and LEAD standard diagnoses for drug and psychiatric disorders. PMID- 1876134 TI - Utility of the Cognitive Status Examination (CSE) for detection of neuropsychological impairment in substance abuse patients. PMID- 1876135 TI - Use of Psychopathy Checklist with opiate addicts. PMID- 1876136 TI - Problems associated with the assessment of personality disorders in substance abusers. PMID- 1876137 TI - Nathan B. Eddy Memorial Award Lecture. PMID- 1876138 TI - Symptom clustering of substance dependence and abuse: examining internal validity of DSM-III, and-IIIR symptom criteria. PMID- 1876139 TI - Cocaine symptoms are predicted by familial psychopathology. PMID- 1876140 TI - Alterations in the distribution of the auditory P300 evoked response potential: similarities between ethanol and divided attention task performance. PMID- 1876141 TI - Nicotine effects in EEG spectral data: smokers vs. non-smokers. PMID- 1876142 TI - Effects of ethanol, diazepam and amphetamines on cerebral metabolic rate: PET studies using FDG. PMID- 1876143 TI - Auditory evoked response brain potentials in individuals at risk for alcoholism: influence of task demands and motivational factors. PMID- 1876144 TI - Cocaine interaction with sulpiride, methysergide, naloxone and desipramine: neurophysiological effects of mesolimbic and neostriatal neuronal activity. PMID- 1876145 TI - Changes in the behavioral effects of cocaine by magnesium in squirrel monkeys. PMID- 1876146 TI - Effects of naltrexone on cocaine self-administration by rhesus monkey. PMID- 1876147 TI - Buprenorphine suppresses cocaine self-administration by rhesus monkeys over 1 to 4 months of daily treatment. PMID- 1876148 TI - Cocaine vs. food choice in rhesus monkeys: effects of increasing the response cost for cocaine. PMID- 1876149 TI - Biological evaluation of compounds for their physical dependence potential and abuse liability. XIV. Animal Testing Committee of the Committee on Problems of Drug Dependence, Inc. (1990). PMID- 1876150 TI - Dependence studies of new compounds in the rhesus monkey and mouse (1990). AB - Norcocaine dose-dependently attenuates abrupt morphine withdrawal in rhesus monkeys. These results suggest a possible role for this metabolite in the interaction of cocaine with the opioid system. PMID- 1876151 TI - Measurement of brain ethanol concentrations in humans with in vivo proton magnetic resonance spectroscopy. PMID- 1876152 TI - Evaluation of new compounds for opioid activity (1990). PMID- 1876153 TI - Immunological function in active heroin addicts and methadone-maintained former addicts: observations and possible mechanisms. PMID- 1876154 TI - The semitic serpent. PMID- 1876155 TI - Marketing the nursing profession. PMID- 1876156 TI - Formative clinical evaluation--quo vadis. PMID- 1876157 TI - Threats to identity. PMID- 1876158 TI - Extreme methods of weaning. PMID- 1876159 TI - [Identification of advocacy intervention in psychiatric nursing]. PMID- 1876160 TI - Stimulating and entertaining the frail aged. PMID- 1876161 TI - AIDS education in schools. PMID- 1876162 TI - Private sector AIDS-testing discouraged. PMID- 1876163 TI - Wither the community health nurse. PMID- 1876164 TI - Doctors urge compulsory AIDS tests. PMID- 1876165 TI - Specializing in midwifery. PMID- 1876166 TI - [The private nurse practitioner]. PMID- 1876167 TI - Smith & Nephew Helpline. Edition 1. PMID- 1876168 TI - Shrinking resources a nursing management perspective. PMID- 1876169 TI - Genetic factors and the psychiatric nurse. PMID- 1876170 TI - [Management of patients with AMS 800 urinary artificial sphincter]. AB - In the following report we would like to describe the role of the nurse in the handling of patients with persistent urinary incontinence and more specifically the patients who have artificial sphincter implants. The success of these implants largely depend on careful evaluation, preparation surgery and follow-up care and it is quite clear that the nurse plays a major role in the team. The purpose of this paper is therefore, to outline the role of the nurse in this process which in turn can serve as a guideline to other centres as they too commence to do these implants. Our experience stems from the fact we have already evaluated +/- 200 patients of which 56 have had the implants. PMID- 1876171 TI - Nursing, a lamp or a limp? PMID- 1876172 TI - A healthier system. PMID- 1876173 TI - [The community health nurse in the next decades]. PMID- 1876175 TI - High HIV infection in Natal. PMID- 1876174 TI - Why AIDS campaigns are not working. PMID- 1876176 TI - Scientific misconduct. FASEB rejects OSI rules. PMID- 1876177 TI - Yeast embryology. Pathways of morphogenesis. PMID- 1876178 TI - Cell biology. Virus receptors as permeases. PMID- 1876179 TI - Neuroscience. Back together again. PMID- 1876180 TI - Sperm competition. PMID- 1876181 TI - Beneficial ghee? PMID- 1876182 TI - Spatial maps. PMID- 1876183 TI - A 'unified theory' of prion propagation. AB - There is now very persuasive evidence that the transmissible agent for spongiform encephalopathies such as scrapie, consists of a modified form of the normal host protein PrPc, devoid of any nucleic acid. On the other hand, because there are many different strains of scrapie agent with distinct phenotypes which can be propagated in animals homozygous for the PrPc gene, it has been suggested that a nucleic acid must be a component of the agent. Can the two views be reconciled? PMID- 1876184 TI - Cloning of a human gene encoding the general transcription initiation factor IIB. AB - Transcription factor IIB (TFIIB) has a central role in transcription of class II genes. The purification of the human TFIIB protein and isolation of a complementary DNA encoding TFIIB activity is reported here. The sequence of TFIIB, which seems to be encoded by a single gene, contains a repeated motif, in addition to a motif with similarity to the prokaryotic sigma-factors. The recombinant protein expressed in bacteria substituted for all the functions attributed to the human TFIIB protein. PMID- 1876185 TI - Evolutionary distinctiveness of the endangered Kemp's ridley sea turtle. AB - The endangered Kemp's ridley sea turtle (Lepidochelys kempi) nests almost exclusively at a single locality in the western Gulf of Mexico, whereas the olive ridley (L. olivacea) nests globally in warm oceans. Morphological similarities between kempi and olivacea, and a geographical distribution that "...makes no sense at all under modern conditions of climate and geography", raise questions about the degree of evolutionary divergence between these taxa. Analysis of mitochondrial (mt) DNA restriction sites shows that Kemp's ridley is distinct from the olive ridley in matriarchal phylogeny, and that the two are sister taxa with respect to other marine turtles. Separation of olive and the Kemp's ridley lineages may date to formation of the Isthmus of Panama, whereas the global spread of the olive ridley lineage occurred recently. In contrast to recent examples in which molecular genetic assessments challenged systematic assignments underlying conservation programmes, our mtDNA data corroborate the taxonomy of an endangered form. PMID- 1876186 TI - Charge movement during Na+ translocation by native and cloned cardiac Na+/Ca2+ exchanger. AB - Na+/Ca2+ exchange is electrogenic and moves one net positive charge per cycle. Although the cardiac exchanger has a three-to-one Na+/Ca2+ stoichiometry, details of the reaction cycle are not well defined. Here we associate Na+ translocation by the cardiac exchanger with positive charge movement in giant membrane patches from cardiac myocytes and oocytes expressing the cloned cardiac Na+/Ca2+ exchanger. The charge movements are initiated by step increments of the cytoplasmic Na+ concentration in the absence of Ca2+. Giant patches from control oocytes lack both steady-state Na+/Ca2+ exchange current (INaCa) and Na(+) induced charge movements. Charge movements indicate about 400 exchangers per micron 2 in guinea-pig sarcolemma. Fully activated INaCa densities (20-30 microA cm-2) indicate maximum turnover rates of 5,000 s-1. As has been predicted for consecutive exchange models, the apparent ion affinities of steady state INaCa increase as the counterion concentrations are decreased. Consistent with an electroneutral Ca2+ translocation, we find that voltage dependence of INaCa in both directions is lost as Ca2+ concentration is decreased. The principal electrogenic step seems to be at the extracellular end of the Na+ translocation pathway. PMID- 1876187 TI - High risk of squamous cell carcinoma of the cervix for women with HLA-DQw3. AB - Many immune responses are controlled by genes of the major histocompatibility complex (MHC). In man these include the loci encoding the HLA-A, -B, -C, -DR, -DQ and -DP antigens, and many diseases have been linked with these. But attempts to identify HLA genes in man that might explain why an immune response against malignant tumours should be ineffective have so far been disappointing, apart from the association reported between the HLA-DR1 antigen and a susceptibility to a rare carcinoma of the thyroid gland. Here we describe another strong connection between a common malignant tumour and an HLA antigen, namely between HLA-DQw3 and squamous cell carcinoma of the cervix: from the 1988 United States tumour registry, 1 in every 63 newborn girls will develop this invasive cancer. We found that 88% of 66 patients had the leukocyte antigen HLA-DQw3 when it would normally be expected in only 50% of individuals. In animals the immune system and the MHC act in defence against virally induced tumours, but until now there has been no evidence that they do so in humans: as squamous cell carcinoma is probably virally induced, our discovery of its association with an HLA antigen will be important to the understanding of the immunogenetic basis of a susceptibility to this tumour. PMID- 1876188 TI - Basal body movements as a mechanism for mitochondrial genome segregation in the trypanosome cell cycle. AB - The mitochondrial genome of Trypanosoma brucei is organized in the form of a complex catenated network of circular DNA molecules. This mass of DNA, known as the kinetoplast, is present at a unique site in the single mitochondrion, and is replicated in a discrete, periodic S phase of the cell cycle. The single-copy nature of the kinetoplast suggests that there is a mechanism ensuring segregation fidelity of replicated copies to each daughter cell. Historically, speculation regarding the nature of this mechanism has often attributed significance to the close association between the kinetoplast and the flagellum basal body. We provide here direct evidence that this mitochondrial DNA complex is indeed linked to the basal body, and segregation of the kinetoplast DNA is dependent on a microtubule-mediated separation of the new and old flagellar basal bodies during the cell cycle. This unique system may represent the remnants of an evolutionarily archaic mechanism for genome segregation. PMID- 1876190 TI - Informatics: here we come. PMID- 1876189 TI - Cloning of an NF-kappa B subunit which stimulates HIV transcription in synergy with p65. AB - The transcription factor NF-kappa B is a protein complex which comprises a DNA binding subunit and an associated transactivation protein (of relative molecular masses 50,000 (50K) and 65K, respectively). Both the 50K and 65K subunits have similarity with the rel oncogene and the Drosophila maternal effect gene dorsal. The 50K DNA-binding subunit was previously thought to be a unique protein, derived from the 105K gene product (p105). We now report the isolation of a complementary DNA that encodes an alternative DNA-binding subunit of NF-kappa B. It is more similar to p105 NF-kappa B than other family members and defines a new subset of rel-related genes. It is synthesized as approximately 100K protein (p100) that is expressed in different cell types, contains cell cycle motifs and, like p105, must be processed to generate a 50K form. A 49K product (p49) can be generated independently from an alternatively spliced transcript; it has specific kappa B DNA-binding activity and can form heterodimers with other rel proteins. In contrast to the approximately 50K protein derived from p105, p49 acts in synergy with p65 to stimulate the human immunodeficiency virus (HIV) enhancer in transiently transfected Jurkat cells. p49/p100 NF-kappa B could therefore be important in the regulation of HIV and other kappa B-containing genes. PMID- 1876191 TI - Cherry: who are you? AB - Do we need a new role model to inspire today's teenagers to look at nursing as a career? If so, who and what should this character be? Billingsley offers her ideas. PMID- 1876192 TI - Learning collaboration in a laboratory setting. AB - Collaboration is a process that contributes in many ways to improved nursing care. Before collaboration can be practiced effectively, the component skills must be learned. This paper describes a course for graduate students that was developed for this purpose. The students learn basic skills in the classroom and apply them to patients in a laboratory setting. An overview of collaboration, the collaboration course, and clinical application is presented. PMID- 1876193 TI - Res ipsa loquitur--putting the health care provider on the hot seat. AB - Just when you thought you knew all of the fine points of malpractice, McMullen describes a new way of getting sued. Fortunately, she also suggests ways to avoid it. PMID- 1876194 TI - The importance of collaboration with staff nurses in the socialization of nursing students. AB - The future of the nursing profession depends on excellent preparation of its students. Vital to this preparation is the cooperation between nurses in education and nurses in service. This article focuses on the promotion of effective collaboration among faculty, staff nurses, and nursing students in the socialization of students into the profession. PMID- 1876195 TI - Intuitive skills in crisis management. AB - This article is a synthesis of nursing and management research findings on intuition and explains why intuition is particularly useful in crisis management. Drawing on applications from organizational psychology, it includes ways to enhance the nurse's ability to exercise and develop intuitive skills. The authors assert that the highly complex, rapidly changing, and often unpredictable circumstances that require crisis management in nursing are best met through applying the complementary cognitive skills of analytic reasoning and intuition. PMID- 1876196 TI - Is national health insurance imminent? AB - What is meant by the rhetoric about "reforming" health care financing and who is driving this movement? Mahrenholz details the whole frightening situation. PMID- 1876197 TI - Pairing students for community health nursing home visits. AB - Faculty paired community health nursing (CHN) students for home visits to reduce students' anxiety and enhance their learning of the nursing process. The pairing method involved 60 students over a three-semester period. The process is described and advantages and disadvantages are analyzed. The net results are favorable. Faculty found that students' fear of entering an unfamiliar home was supplanted by a sense of challenge at working collaboratively with a peer. Furthermore, the pairing experience increased students' confidence in making decisions about client care and offered them more physical safety when visiting high-crime urban settings. Students felt positive about the increased safety and expressed greater confidence in their CHN role and their application of the nursing process. PMID- 1876198 TI - Ethics, policy, and allocation of scarce resources in nursing service administration: a pilot study. AB - Between the 10-year projection of a half million FTE nursing shortage, astronomical medical care costs and a lingering recession, nursing administrators have no option but to make difficult choices in resource allocation. What are the ethics inherent in such a situation? Silva & Lewis reveal the opinions of current nurse leaders. PMID- 1876200 TI - The Oncology Nursing Society. AB - Oncology nursing is one of the fastest moving and most exciting specialties in nursing today. ONS, not surprisingly, is one of the strongest specialty groups. Taylor profiles the history of this group. PMID- 1876199 TI - Multiple mentoring strategy in the academic preparation of quality assurance directors. AB - Availability of adequately educated and trained nursing quality assurance directors is a must for the survival of health care institutions. Educators meet many challenges in preparing masters students for this role. Issues pertaining to definition of a relevant course of study in theoretical and practical content areas, and faculty's lack of personal experience with the role are situations that must be resolved. This article describes a model of multiple mentoring through collaboration that was implemented at a large urban nursing department with satisfactory solutions. PMID- 1876201 TI - Some inflammatory observations. PMID- 1876202 TI - It's not always "better to be safe than sorry": a fourth amendment restriction on mandatory AIDS testing. PMID- 1876203 TI - Arterial aneurysms. PMID- 1876204 TI - Management of the infant with meconium stained amniotic fluid. PMID- 1876205 TI - [Correlations between thalamic projections to different areas of the parietal association cortex of the cat]. AB - Projections of thalamic neurons to parietal association cortex of cat were examined by means of the retrograde axonal transport of fluorescent dyes (primuline and fast blue). It has been demonstrated that a dorsal part of the pulvinar (PL) and a dorsal part of the caudal area of the lateral posterior nucleus (LP) projected mostly to the middle suprasylvian gyrus (MSSG), while a ventral part of PL and a ventral part of the rostral area of LP--to the rostral suprasylvian gyrus (RSSG). Double labelled neurons were found in PL, LP, suprageniculatus, anterior ventral, ventral lateral as well as in the central lateral, paracentral and central medial nuclei after injections of two different dyes into MSSG and RSSG. Topic organization of sources of cortical projections from the PL--LP complex can probably provide a high level of discrimination of visual signals by single cortical neurons. At the same time during integration of information of a different subcortical origin RSSG and MSSG act, probably, in concord to a considerable extent, that suggests insufficient differentiation of RSSG and MSSG corresponding approximately to cortical areas 5 and 7 of cat. PMID- 1876206 TI - [Changes in quantitative characteristics of the efferent activity of the locomotor generator after decerebellation]. AB - Quantitative changes of efferent activity parameters of the locomotor generators of hindlimbs were investigated after decerebellation on the decerebrated immobilized cats. Removal of modulating influences of the cerebellum on nuclei of descending systems caused an insignificant increase in the activity of the generator half-centre, increased instability of the generator functioning, diminished the statistical dependence between changes in parameters of the activity of the generator half-centres and strengthened the generators' sensitivity to afferent signals. The functional significance of descending signals in functioning of the locomotor and scratch generators is discussed. PMID- 1876207 TI - [Rearrangement of the efferent activity of a locomotor generator under electric activation of descending systems in immobilized cats]. AB - Rearrangement of the locomotor generator activity evoked by phasic electrical stimulation of different descending systems has been investigated on decerebrated immobilized cats. The rearrangement heavily depends on the stimulation phase. A maximal increase of the locomotor cycle duration by electrical stimulation of the Deiters nucleus takes place in the end of an "extensor" phase. Stimulation of the Deiters nucleus during the flexor phase decreases the locomotor cycle duration. A maximal increase of the locomotor cycle duration by electrical stimulation of the red nucleus, pyramidal tract and reticular gigantocellular nucleus takes place in the first half of a "flexor" phase. Electrical activation of these descending pathways during the flexor phase promotes an increase in intensity of this phase and a decrease in intensity of the "extensor" phase. Electrical activation of the Deiters nucleus increases intensity of the extensor phase and decreases that of the "flexor" phase. Possible principles of the suprasegmental correction of the locomotor generator activity are discussed. PMID- 1876208 TI - [Structure of receptive fields of visually sensitive neurons of the cat hippocampus]. AB - Structure of receptive fields of visually sensitive neurons in areas CA1 and CA3 of the dorsal hippocampus was investigated in alert cats with the brain-stem pretrigeminal section. The receptive field (RF) structure of 76 hippocampal neurons was analyzed by methods of scanning the RF by moving stimuli and mapping all their surface by a stationary flashing spot. According to presented data the neurons were classified into three groups: neurons with homogeneous structure of the RF (54%), with nonhomogeneous (28%) and neurons more sensitive to stimulus motion (18%) than to a stationary flashing light. Experiments have shown that responses of hippocampal neurons are highly specific ones. Thus, 9% of neurons with the nonhomogeneous RF structure have shown specific responses to variation of the contrast and contours of moving stimuli. The presented results show that hippocampal visually driven neurons have well developed mechanism for processing visual sensory information and apparently this quality ensures participation of the limbic system in visually controlled behavior of the animal. PMID- 1876209 TI - [Reciprocal modulating effect of serotonin and dopamine on neurons of rat spinal ganglia]. AB - It was found in experiments on isolated dorsal root ganglion neurons of rats that dopamine (10(-8)-10(-6) Mol/l) potentiated depolarizing neuronal responses evoked by injection of 5-hydroxytryptamine from micropipette. Similar concentrations of 5-hydroxytryptamine (10(-8)-10(-6) Mol/l) potentiated neuronal depolarizing responses evoked by dopamine. Potentiating action of monoamines on combined neuronal responses depended on concentration and was inhibited by antagonists of dopamine (haloperidol) and 5-hydroxytryptamine (deseril) receptors. This effect of monoamines had postsynaptic nature and was bound with an increase of Ca2+ and cAMP intracellular concentrations. PMID- 1876210 TI - [Inhibiting effect of the presentation of additional stimuli on neuronal responses in the cat sensorimotor cortex during a conditioned reflex]. AB - Conditional responses of the sensomotor cortex neurons were registered in awake cats which were trained to respond to presentation of conditional stimuli (a single sound click) by instrumental conditional movement. Those neuronal responses were registered 50-150 ms before realization of reflex movements. During external stimulation after the reflex beginning, conditional neuronal reactions appeared 50-250 ms later, but the latencies of conditional movements did not change. It is supposed that the studied phenomenon is a result of the growing exteroceptive attention of cats to external stimulation. PMID- 1876211 TI - [Effect of local superficial cooling of the rat cerebral cortex on unit activity of neurons--hypothetical sources of corticofugal signals]. AB - Unit activity and primary responses (PR) in the cortex area SI and evoked potentials (EP) in the striatum of the rat's brain were recorded during electrocutaneous stimulation of the contralateral forepaw. The cortex in the area of sensory representation of the stimulated extremity was cooled superficially, which promoted an increase of the PR amplitude in the cooling zone. Such cooling facilitated EP to the same stimulus in the striatum. The facilitation was accompanied by changes in time parameters of the neuronal responses in the 5th and 6th layers of the cortex: the latency and spike responses increased, a rhythmic organization of the responses either appeared or (if it was presented before cooling) became more intensive and period of the rhythm got longer. An increase in the spike number and amplitude of PR evoked by cooling in response to applied stimulus was not so high as an increase in the EP amplitude in the striatum and did not completely coincide with it in time. The data obtained permitted suggesting that the effect of corticofugal signals on the sensory reaction in the striatum was rather due to their time organization then to intensity. PMID- 1876212 TI - [Unit activity in the thalamic reticular nucleus during external stimulation in cats taught an instrumental conditioned reflex]. AB - Application of heteromodal extrastimuli (ES) promotes selected excitation of most of the responding neurons in the thalamic reticular nucleus (R). Twelve of 32 tested neurons responded to visual ES and 4 from 21 tested neurons responded to auditory ES. Initial responses of neurons and quantity of cells with initial responses decreased during habituation to ES. Grouped discharges disappeared after external stimulation. Initial responses to ES and to the following conditional stimulus appeared during external inhibition (EI), while late responses usually accompanying conditioning were inhibited almost in half of the studied neurons. It was suggested that R neurons participated in EI and in habituation to ES. PMID- 1876213 TI - [Effect of nucleus entopeduncularis stimulation on thalamic nuclei motor neurons under normal conditions and after injury of the nigrostriatal dopaminergic system produced by the neurotoxin MPTP]. AB - Two groups of acute experiments were performed on cats anesthetized by ketamine and immobilized by myorelaxine to study reactions of neurons in ventral anterior (VA) and ventral lateral (VL) thalamic nuclei to stimulation of nucleus entopeduncularis (nEp) in normal animals and in those treated with chronic injections of neurotoxin--N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 5 mg/kg, i.m., daily, for five days). It was established that in normal cats 28% of the neurons studied have responded to nEp stimulation by inhibition with the latency shorter than 7 ms. In a half of inhibiting neurons after the first phase of inhibition which lasted 18 +/- 2 ms, the second inhibitory phase was registered. The duration of the latter was 25 +/- 4 ms. In MPTP-treated cats the number of neurons inhibited after nEp stimulation was practically the same as in normal ones (24.5%). A tendency of the first phase shortening and a statistically significant increase of the second inhibition phase duration up to 50 +/- 11 ms were found. It was suggested that changes in the inhibitory processes in VA-VL neurons receiving afferents from nEp might be explained by hyperpolarization of the nerve cell membrane evoked by increasing pallidothalamic inhibitory influences. That hyperpolarization created conditions for a decrease in Cl(-) dependent and an increase in Ca(2+)-dependent K(+)-related phases of inhibitory postsynaptic potentials. PMID- 1876214 TI - [Preganglionic parasympathetic innervation of the intact and partially denervated rat stomach]. AB - The preganglionic parasympathetic innervation of normal and vagotomized rat stomach have been investigated by the horseradish peroxidase (HRP) technique. After the HRP injection into the antrum and fundus muscles the labelled cells were revealed in nuclei dorsalis nervi vagi bilaterally, but preferentially in the left nucleus. The most numerous labelled cells were observed after injection into the region of the curvatura minor. When HRP was injected into the vagotomized stomach one, three, four and six months after the surgery procedures the labelled cells in the nuclei nervi vagi were not revealed. Mechanisms of regeneration of nervi vagi efferents and normalization of the stomach activity are discussed. PMID- 1876215 TI - [Effect of temperature and emotional factors on the catecholamine content in intestinal and splenic adrenergic plexuses of celiac plexus-decentralized rats]. AB - Effects of temperature and emotive factors on the catecholamine content in intestinal and splenic adrenergic plexuses of celiac plexus-decentralized rats have been studied using histofluorescence and computer analysis. It is shown that the catecholamine content in the plexuses gets higher during hypothermia and remains unchanged during hyperthermia and emotional stress. PMID- 1876216 TI - [Afferent projections of the bulbar locomotor region located in the medial reticular formation of the brain stem]. AB - Afferent projections to the functionally identified bulbar locomotor region which is situated in the medial reticular formation were studied in cats and rats by means of horse-radish peroxidase technique. Cells of origin of such projections were found not only in hypothalamic and mesencephalic locomotor regions but also in the interstitial nucleus of Cajal and adjacent structures and in the ventral part of the caudate nucleus. PMID- 1876217 TI - [Cluster headache and chronic paroxysmal hemicrania: current therapy]. AB - In acute attacks of cluster headache (CH), the mainstays of treatment are inhalation of pure oxygen (due to lack of any side effects), ergotamine aerosol, and intranasal application of local anaesthetics. The following treatments have hitherto been recommended for the prevention of attacks: young patient with first manifestation-methysergide; middle aged patient with episodic or chronic CH steroids; older patient with history of resistance to therapy-lithium. These guidelines have been superceded as a result of the demonstration of the efficacy of several other drugs which have reduced side effects. This increased variety of treatments also reduces the importance of clinical differentiation between episodic and chronic cluster headache. Today, the drugs of first choice for treatment of episodic cluster headache are steroids or calcium channel blockers like verapamil, replacing methysergide which is now drug of second choice. In chronic CH, verapamil and lithium are normally prescribed, steroids-possibly in combination with one of the other drugs-are regarded as drugs of second choice. Another possibility, used with increasing frequency, is valproate acid, and the experimental drug budipine may be a further alternative in therapy resistant patients. There is no convincing role for invasive surgical procedures, particularly in the light of the increased number of effective drugs. The treatment of choice for chronic paroxysmal hemicrania is indometacin, although individual patients may respond to salicylates, naproxene, prednisone and ergotamine. PMID- 1876218 TI - [Transcranial magnetic stimulation in psychogenic paralysis]. PMID- 1876219 TI - [Diagnostic tests in carpal tunnel syndrome]. AB - In a first series 100 patients underwent surgical treatment for carpal tunnel syndrome (CTS) after being tested by provocative tests for sensory disturbances preoperatively. In addition to the well-established tests like passive wrist flexion (Phalen's test) or wrist extension, active movement tests of the patient against resistance were investigated. Tests of active movement were introduced because of the high values of intraoperatively measured pressure at the median nerve, similar to those recorded with passive movements. All investigated provocative tests for sensory disturbances related to CTS, investigated by active and passive movements, were positive in 72% to 84% of patients. Average delay times for reaction of these provocative tests ranged between 15.7 and 19.5 s. Furthermore Tinel's sign showed a sensitivity of 64% and the flick sign one of 69%. The specificity of tests and signs for the CTS was assessed on a group of 50 surgically treated patients with cervical nerve root entrapment at the C5-C8 level. In this group and a second CTS group the most sensitive of each test in the first series (active and passive provocational movement), Tinel's sign and flick sign were investigated. By forming subgroups in both diseases we showed that the results of the total groups were not influenced by a possible double crush. We could demonstrate high sensitivities in cervical nerve root entrapment for Phalen's sign with 74% and for active thumb abduction with 68% and a medium sensitivity for Tinel's sign with 40%--thus implying low specificity for CTS. Only the flick sign turned out to be relatively specific for CTS--its sensitivity in cervical nerve root entrapment was around 26%--indicating its potential to function as a valid criterion for the differential diagnosis of CTS and cervical nerve root entrapment syndrome. PMID- 1876220 TI - [Significance of dystrophin analysis in adult myopathies. Study methods, case reports and current pathogenetic considerations]. PMID- 1876221 TI - [Eosinophilia-myalgia syndrome]. AB - The following is an outline of one typical case of chronic eosinophilia-myalgia syndrome (EMS). In 1987 a 62-year-old woman began taking L-tryptophan, 1.5 g nightly, due to sleeping difficulty. During the months preceding the appearance of EMS she continued to take L-tryptophan, derived from the biosynthetic production of the Japanese manufacturer "Showa Denko". She has suffered increasingly from severe myalgia and a proximal muscle weakness since July of 1989. In November, 1989 her white blood cell count measured 12.1 X 10(9)/l with 3.6 X 10(9) eosinophil cells/l. The bone marrow exhibited an increased granulopoesis and an extreme increase in the amount of eosinophil cells. The muscle biopsy specimen indicated an inflammation with perivascular distribution. The eosinophil cell count of the blood was quickly normalized via the introduction of prednisone over a short period. In the absence of further immunosuppressive therapy a slow improvement can be seen in the myalgia and in her general condition. Since the beginning of 1990 there has been a slow development of hyperpigmented scleroderma-like skin changes with distal distribution. PMID- 1876222 TI - [Chronic hyperthyroid myopathy. A contribution to the differential diagnosis of myopathic limb-girdle syndrome]. PMID- 1876223 TI - [Symptomatic cluster headache: coincidence or causal relation? Report of six cases]. PMID- 1876224 TI - [Dystrophia myotonica (Steinert disease)--a frequently misdiagnosed disease]. PMID- 1876225 TI - Muscarinic acetylcholine receptor subtype mRNA expression and ligand binding in the aged rat forebrain. AB - Previous studies indicate that a 20-30% decline in muscarinic acetylcholine receptor binding occurs in localized areas of rat brain during aging. In this study, reduced [3H]-quinuclidinyl benzilate binding was observed in striata from 24-25-month-old rats relative to 5-6-month-old animals using homogenate binding assays. To determine if the decline in receptor concentration occurs as a result of decreased receptor synthesis, the expression of the m1, m3, and m4 muscarinic receptor mRNAs as well as [3H]-QNB binding were determined in adjacent sections of young and old male rats using in situ hybridization and in vitro receptor autoradiography respectively. A significant decline in collective muscarinic receptor binding as assessed by [3H]-QNB was observed in the caudate putamen, olfactory tubercle, nucleus accumbens, and several frontal and parietal cortical areas. The only difference observed in muscarinic mRNA expression for any of the three subtypes examined was a decline in m1 hybridization in the olfactory tubercle. The results of this study demonstrate that the regional brain areas displaying age-related decreases in receptor binding do not correlate with those areas showing a decrease in muscarinic receptor expression. Apparently, the decline in muscarinic acetylcholine receptor density with age does not result from a decline in receptor gene expression. PMID- 1876226 TI - Functional elongation of CA1 hippocampal neurons with aging in Fischer 344 rats. AB - Dendritic function of CA1 pyramidal cells was measured during intracellular recording in vitro and correlated with in vivo behavior in Fischer 344 rats. The aged rats (greater than 26 months) were significantly impaired on a water maze test of hippocampal behavioral function. CA1 neurons from these aged rats demonstrated an elevated action potential threshold compared to the young rats. Electrotonic length (L, in lambda), calculated independently from physiological transients and electrotonic cell reconstructions, was significantly longer in neurons from aged rats (L = 0.73 +/- 0.02 lambda; mean +/- SEM) than in neurons from young rats (L = 0.66 +/- 0.02 lambda). Analysis of proximal and distal synaptic potentials pointed to a more distal electrotonic siting of all dendritic synapses in the aged neurons. Thus, electrical lengthening of dendrites, alterations in synaptic location and decreased excitability in neurons from aged rats with behavioral impairment may represent an endpoint of neuronal reactive mechanisms in response to the aging process. PMID- 1876227 TI - Effect of age on blood vessels and neurovascular appositions in the CA1 region of the rat hippocampus. AB - Rats aged 3, 9, 24 and 30 months were used in this study. Increased basal lamina thickening in capillaries, muscular large vessels and nonmuscular large vessels was shown with advancing age. There is also an age-related increase in the area of mitochondria in smooth muscle cells. These ultrastructural changes may underlie observed age-related functional changes in the vasculature. They may be a compensatory response of the vessel wall cells to a declining capacity to handle the continual and varying shear stress exerted by the blood. Ultrastructural differences between capillaries and the two types of large vessels are reported and discussed in terms of their functional significance. It was noted that there are more dendrites adjacent to capillaries than to large vessels, however, this was unaffected by increasing age. Since advancing age did not alter the number of neuronal processes adjacent to vessels, age-related compromises in vessel function may not be subjected to neuronal regulation. PMID- 1876228 TI - Beneficial effects of nicotine administered prior to a delayed matching-to-sample task in young and aged monkeys. AB - Our earlier studies have demonstrated that administration of low micrograms/kg doses of nicotine to young adult monkeys prior to a delayed matching-to-sample (DMTS) task resulted in a centrally mediated improvement in performance of the task, particularly when delay intervals which most greatly challenged the animal's capabilities were involved. The present study confirmed these findings using a completely computer driven and automated procedure. In addition, performance on the DMTS was observed to be enhanced when animals were again tested 24 h after the dose of nicotine. Further analysis of the data indicated that the majority of enhancement to nicotine could be accounted for by a greatly increased performance at the least preferred stimulus color. Position preference (left vs. right stimulus) was not a factor in nicotine-induced enhancement. Two aged monkeys (34 years old Macaca mulatta) were significantly more difficult to train in the DMTS task and their longest delay capabilities were significantly shorter than the young animals (Macaca fascicularis). Nevertheless, the aged animals were essentially similar in most respects in their responses to nicotine administration. These data are consistent with a role for central nicotinic systems in memory performance and with the ability of nicotine to produce enhancement of selective features of mnemonic strategy in young and old monkeys. Furthermore, it is possible that either model, the aged animal, or the young animal stressed to his mnemonic capability may provide a good model for learning and memory disorders in humans. PMID- 1876229 TI - Loss during aging of beta-endorphinergic neurons in the hypothalamus of female C57BL/6J mice. AB - Beta-endorphin (B-EP) content is often reduced in hypothalami of aging rodents. The objective of this study was to determine whether reduced B-EP content is associated with a reduced number of B-EP immunoreactive neurons. Serial coronal sections extending from the caudal hypothalamus through the retrochiasmatic area were examined by quantitative light microscopy in mature (5-6 month) and senescent (24-28 month) mice that had been ovariectomized 1 week earlier and injected with colchicine 24-48 h before sacrifice. Old mice were acyclic. As expected, B-EP immunoreactive cell bodies were restricted to the region of the arcuate nucleus. There was a 35% loss of B-EP immunopositive neurons in old, macroscopically disease-free animals. By contrast, some old animals with pituitary tumors had no loss of B-EP neurons. These results suggest that a subpopulation of B-EP neurons either die or stop synthesizing detectable concentrations of B-EP in aged mice. The basis for the absence of reduced B-EP neurons in some mice with pituitary tumors is unclear, but this observation underscores the importance of distinguishing age-related changes associated with diseases of aging from those that are independent of such diseases. PMID- 1876230 TI - Subcortical hyperintensities on brain magnetic resonance imaging: a comparison between late age onset and early onset elderly depressed subjects. AB - Subcortical structural changes have been reported to occur in some elderly subjects with late age onset depression. Given the association between diseases affecting subcortical structures and affective disorders, this suggests that these structural changes may be involved in the etiology of late age onset depression in some patients. With the advent of Brain Magnetic Resonance Imaging (MRI), "in vivo" analysis of these subcortical structures is now possible. The authors report a higher occurrence of caudate (60% vs. 11%) and large deep white matter hyperintensities (60% vs. 11%) in late age onset elderly depressed subjects compared with early onset elderly depressed subjects. These results suggest that late age onset depression may be mediated by caudate and white matter structural changes in some patients. PMID- 1876231 TI - The effects of age on eyeblink conditioning in the freely moving Fischer-344 rat. AB - The effects of age were assessed on the ability of male Fischer-344 rats to acquire a classically conditioned eyeblink using the "delay" paradigm. Using a 350 ms white noise conditioning stimulus and a 100 ms coterminating periorbital shock (2 mA, 60 Hz, AC) we have demonstrated that these rats exhibit deficits as early as middle age. Middle-aged and senescent rats (18 and 30 months) exhibited significantly fewer conditioned responses than young rats (3 and 12 months). Since all of the rats responded to a test noise, and there were no differences in threshold to evoke a blink, this result is likely to be due to an associative deficit. Thus, our results indicate that eyeblink conditioning in the freely moving rat is a useful model system for behavioral and neurobiological analyses of the effects of age on associative learning and memory. PMID- 1876232 TI - Nicotinic cholinoceptive neurons of the frontal cortex are reduced in Alzheimer's disease. AB - The cellular distribution of nicotinic acetylcholine receptors was studied in the frontal cortex (area 10) of 1) Alzheimer patients and compared to 2) age-matched and 3) middle-aged controls using the monoclonal antibody WF 6 and an immunoperoxidase protocol. Statistical analysis revealed significant differences between the number of labeled neurons among all three groups tested (middle-aged controls greater than aged controls greater than Alzheimer cases). No differences were seen for cresyl violet-stained samples. These findings underline that the nicotinic receptor decrease found with radioligand binding may reflect a postsynaptic in addition to a presynaptic component. PMID- 1876233 TI - Restoration of circadian corticosterone rhythm in ventromedial hypothalamic lesioned rats. AB - The effects of ventromedial hypothalamic (VMH) lesions on the circadian periodicity of blood corticosterone were studied in female rats. The rats were kept on a 12-hour light/12-hour dark illumination regimen and fed ad libitum. Three, 10 and 12 weeks after the VMH lesions, the concentrations of blood corticosterone were measured every 4 h for 48 h in the same unanesthetized rats. Three weeks after the operation, the circadian rhythm in VMH-lesioned rats was disturbed and disappeared. The corticosterone levels at 03:00, 07:00, and 11:00 were significantly higher than those in sham-operated rats. 10 and 12 weeks after the operation, the circadian rhythm, however, was notable (p less than 0.05, p less than 0.05). The elevated mean corticosterone levels over 48 h at 3 weeks after the operation decreased at 10 and 12 weeks. The sham-operated rats showed a significant circadian rhythm at 3, 10 and 12 weeks after the operation (p less than 0.001 in each period) with a peak concentration at 19:00 and through at 07:00. These findings show that the corticosterone circadian rhythms which were disturbed in the dynamic phase after VMH lesions recovered in the static phase of obesity, suggesting that the ventromedial hypothalamus is not an essential biological clock of circadian corticosterone rhythm. PMID- 1876234 TI - Chronic sodium or chloride depletion upregulates angiotensin II receptors in the anterior pituitary lobe of young rats. AB - The effect of chronic (35 days) and selective sodium or chloride depletion on the regulation of angiotensin II receptors in the anterior pituitary gland of young male rats was studied by quantitative autoradiography. Both chronic sodium or chloride depletion produced significant extracellular fluid volume contraction, stimulation of the circulating renin-angiotensin system and increased the number of angiotensin II receptors in the anterior pituitary gland. Changes in angiotensin II receptors in both sodium- and chloride-depleted animals were associated with increased plasma prolactin levels. Our results suggest a participation of the pituitary renin-angiotensin system in the physiological response and/or possible adaptation to chronic sodium or chloride depletion. Extracellular fluid volume contraction and profound chronic stimulation of the circulating renin-angiotensin system may contribute to regulate anterior pituitary angiotensin II receptors and may influence prolactin release. PMID- 1876235 TI - Differential early time course activation of the brainstem catecholaminergic groups in response to various stresses. AB - The effects of various stressors (restraint, ether, histamine and insulin-induced hypoglycemia stress) on the early time course activation of the different catecholaminergic (CA) cell groups A1/C1, A2/C2 and locus ceruleus (LC) from the brainstem were studied. The activity of the central noradrenergic neurons was assessed by measuring in tissue punches the 3,4-dihydroxyphenylacetic acid (DOPAC) level, a side metabolite of noradrenaline (NA) and adrenaline biosynthesis that is thought to reflect the activity of NA cells. Short 5 min restraint stress led to an immediate increase of DOPAC level in the three CA groups. In the A1/C1 and A2/C2 groups the maximal increase, respectively +75 and +50%, was already reached at the end of the application of the stress while for the LC the maximum (+84%) was obtained 15 min after the onset of the stress. Return to baseline level was achieved within 2 h. Continuous immobilization stress did not further alter the DOPAC concentration in the LC and the A1/C1 while a progressive increase up to 85% in the A2/C2 group was seen over 20 min. Following a 2-min exposure to ether, DOPAC was increased in all three structures within 5 min. At this time the maximum was already reached in the A1/C1 and LC, respectively +99 and +43%. After histamine or insulin injection DOPAC level increased in the A1/C1 and A2/C2 in the +25/+50% range but was not significantly affected in the LC. In all the stress situations studied the increase in DOPAC level, particularly in the A1/C1 group always preceded or was concomitant to the increase of plasma corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876236 TI - Exogenous growth hormone inhibits bovine but not murine pituitary growth hormone secretion in vitro: evidence for a direct feedback of growth hormone on the pituitary. AB - To test the hypothesis that one aspect of growth hormone (GH) regulation involves a direct effect of GH on its own secretion at the level of the pituitary, we evaluated the effects of human GH on basal and GH-releasing factor (GRF)-induced GH secretion in rat and bovine pituitary cell cultures. Both 4 h (acute) and 24 h (chronic) exposure of bovine pituitary cells to exogenous human GH significantly (p less than 0.001) reduced GH secretion. Acute treatment resulted in a decrease in GH secretion from 579 +/- 24 to 500 +/- 17 ng/ml 4 h (mean +/- SEM, n = 24) while chronic treatment resulted in a GH decrease from 595 +/- 21 to 483 +/- 17 ng/ml/4 h. In contrast, human GH treatment of rat somatotropes had no effect on basal GH secretion. GRF-stimulated GH secretion was not affected by either acute or chronic GH exposure in either species. These results demonstrate that there are species-specific differences in the ability of GH to regulate its own secretion and provide evidence for a direct inhibitory effect of GH at the level of the bovine pituitary. PMID- 1876237 TI - Estradiol rapidly stimulates dopamine release from the posterior pituitary in vitro. AB - Dopamine (DA) from both the posterior pituitary (PP) and stalk-median eminence (SME) inhibits prolactin (PRL) secretion from the anterior pituitary. Estradiol participates in the regulation of PRL release, in part by modulating DA release from the SME. However, little is known concerning the effects of estradiol on the release of DA from the PP. The objective of this study was to examine whether estradiol rapidly affects the potassium-evoked release of endogenous DA from the PP and SME in vitro. Tissues were dissected from ovariectomized rats and allowed to equilibrate in media for 30 min. Two pulses of 28 mM K+, 3 min each, were then given 30 min apart. Test substances were added 20 min before the second stimulus. DA in the media was determined by HPLC. Estradiol, at a concentration of 1 and 10 nM, significantly stimulated the potassium-evoked DA release from the PP by 34 and 47%, respectively. This stimulation was specific since 17 alpha-estradiol, a biologically inactive isomer, and testosterone, were without effects. Estradiol did not alter DA release from either the SME or isolated neural lobes of the PP. Naloxone, an opioid receptor antagonist, abolished the estradiol-induced stimulation of DA release from the PP. In contrast, amphetamine, a DA-releasing agent, significantly increased DA release in the presence of naloxone. In conclusion, (1) estradiol stimulates DA release from the PP but not the SME or neural lobe; this effect is rapid and stereospecific, and (2) the effects of estradiol appear to be mediated via an opioid(s) peptide(s) from the intermediate lobe. PMID- 1876238 TI - Sex difference in estradiol regulation of progestin receptor mRNA in rat mediobasal hypothalamus as demonstrated by in situ hybridization. AB - Previous studies have shown that estrogen increases the level of progestin receptors (PR) to a greater extent in female than in male rat hypothalamus. In order to determine if sex-specific regulation of the PR protein might be attributable to estrogenic effects on the PR message, in situ hybridization was used to assess sex differences in levels of estrogen-inducible PR mRNA in specific brain nuclei. Here, we report a sexually differentiated pattern of estrogen-regulated PR gene expression. In female hypothalamus, estrogen administered to gonadectomized rats induced a 3.6- and a 3.3-fold increase in PR mRNA in the ventrolateral aspect of the ventromedial nucleus and arcuate nucleus, respectively, but failed to alter the level of PR mRNA in the same neuronal groups of the male. Hormone treatment did not affect the levels of PR mRNA in the dorsomedial or medial amygdaloid nuclei of either sex. These results lead towards a molecular explanation of sex differences in female reproductive behavior by revealing an estrogen-dependent up-regulation of the message for PR, a transcription factor, in a region- and sex-specific fashion. PMID- 1876239 TI - Production of a growth hormone-releasing hormone-like peptide and its mRNA by human lymphocytes. AB - Human peripheral blood lymphocytes (PBL) contain immunoreactive growth hormone releasing hormone (irGRH). Both the intracellular content and the release of irGRH from PBL are increased following lymphocyte activation. Although binding of lymphocyte-derived irGRH to a GRH1-44 antibody dilutes in parallel with standard GRH1-44, irGRH elutes earlier on gel chromatography with an apparent molecular weight of approximately 50 kD. On reverse-phase high performance liquid chromatography, irGRH elutes later than GRH1-44. Northern blot analysis also detected the presence of two GRH mRNA transcripts in PBL, one similar in size to the hypothalamic species of 0.75 kb and another larger transcript of approximately 10 kb. Despite these differences in physicochemical behaviour, both the lymphocyte-derived irGRH GRH1-44 were biologically active as demonstrated by enhancing the transcription of growth hormone mRNA both in dispersed rat pituitary cells and in PBL. PMID- 1876240 TI - Symptomatic Chiari malformation in adults: a new classification based on magnetic resonance imaging with clinical and prognostic significance. AB - Thirty-five consecutive adults with Chiari malformation and progressive symptoms underwent surgical treatment at a single institution over a 3-year period. All patients underwent magnetic resonance imaging scan before and after surgery. Images of the craniovertebral junction confirmed tonsillar herniation in all cases and allowed the definition of two anatomically distinct categories of the Chiari malformation in this age group. Twenty of the 35 patients had concomitant syringomyelia and were classified as Type A. The remaining 15 patients had evidence of frank herniation of the brain stem below the foramen magnum without evidence of syringomyelia and were labeled Type B. Type A patients had a predominant central cord symptomatology; Type B patients exhibited signs and symptoms of brain stem or cerebellar compression. The principal surgical procedure consisted of decompression of the foramen magnum, opening of the fourth ventricular outlet, and plugging of the obex. Significant improvement in preoperative symptoms and signs was observed in 9 of the 20 patients (45%) with syringomyelia (Type A), as compared to 13 of the 15 patients (87%) without syringomyelia (Type B). Postoperative reduction in syrinx volume was observed in 11 of the 20 patients with syringomyelia, including all 9 patients with excellent results. Magnetic resonance imaging has allowed a classification of the adult Chiari malformation in adults based on objective anatomic criteria, with clinical and prognostic relevance. The presence of syringomyelia implies a less favorable response to surgical intervention. PMID- 1876241 TI - Conservative treatment of patients with acoustic tumors. AB - Seventy of 178 patients with acoustic tumors initially were treated conservatively and have been followed up for an average of 26 +/- 2 months. The tumor size was determined by the mean maximum anteroposterior and mediolateral diameters, using computed tomographic or magnetic resonance imaging scans obtained sequentially throughout the follow-up period. The average tumor growth was 1.6 +/- 0.4 mm the 1st year, and 1.9 +/- 1.0 mm the 2nd year (range, -2 to 17 mm/y): 4 tumors showed apparent regression, 28 (40%) had no detectable growth, and 37 (53%) exhibited growth (average, 3.8 +/- 1.2 mm/y). Within individual patients, the tumor growth rate determined during the 1st year of follow-up was predictive of tumor growth rate determined during the following year. Rapid tumor growth or clinical deterioration in 9 of the 70 patients (13%) who initially were treated conservatively necessitated subsequent surgery an average of 14 +/- 5 months after the patient was initially seen. This group had a larger initial tumor size (27.0 +/- 3.4 mm vs. 21.3 +/- 0.9 mm, P less than 0.05), and a faster 1-year growth rate (7.9 +/- 2.3 mm/y vs. 1.3 +/- 0.3 mm/y, P less than 0.05) than the 61 patients who did not require surgery. Two patients, however, experienced neurological deterioration that required surgery, even though there was no tumor growth. The high incidence of acoustic tumors with no detectable growth or apparent spontaneous regression must be taken into account when evaluating the indications for surgery and the efficacy of radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876242 TI - C6 glioma-astrocytoma cell and fetal astrocyte migration into artificial basement membrane: a permissive substrate for neural tumors but not fetal astrocytes. AB - Cortically homografted C6 glioma-astrocytoma cells both invade the rat host brain as a mass and migrate as individual cells. In contrast, fetal astrocytes derived from homografted whole pieces of fetal cortex migrate only as individual cells throughout the brain of the rat but are not capable of invasion. Our experiment explored the migratory capacity (over 7 days) of cultured purified fetal astrocytes and C6 cells after seeding 10(6) cells on a hydrated artificial basement membrane wafer (Matrigel). The artificial basement membrane wafer was not a suitable substrate for the growth of cultured fetal astrocytes. In contrast, C6 cells migrated as individual cells from the surface of the wafer into the substrate. Individual C6 cells migrated 1.8 mm in the first 4 days and then ceased migration. The C6 cells were observed at the base of a digestion tube that extended from and was open to the surface of the wafer. At 3 days, micropockets were observed to form around each C6 cell at the base of each tube. By 7 days, the majority of pockets observed were large and contained several C6 cells. These multiple cell groups appeared to be progenitors of tumor masses. These data indicate that C6 glioma-astrocytoma cells, which in vivo appear to be a model for glioblastoma multiforme, primarily migrate as individual cells through artificial basement membrane and secondarily form tumor masses. Progenitor tumor masses form by coalescence of individual C6 cell micropockets or the division of a single cell in an individual micropocket. PMID- 1876243 TI - Posterior fossa ependymomas: report of 30 cases and review of the literature. AB - Thirty patients with histologically confirmed posterior fossa ependymomas operated on between January 1976 and December 1988 were reviewed. The median age was 44 years (range, 1-69 yr). There were 7 children (aged 5 yr or younger) and 23 adults (aged 16 yr or older). There were 18 female patients and 12 male patients. Headache, nausea and vomiting, and disequilibrium were the most frequent symptoms. The most common findings were ataxia and nystagmus. Gross total resection was performed in 8 patients (27%), subtotal resection in 21 patients (70%), and biopsy in only 1 patient (3%). Tumors were low grade in 73% and high grade in 27%. Twenty-seven patients underwent posterior fossa radiotherapy (median dose, 5400 cGy). Fourteen patients also underwent spinal irradiation (median dose, 3520 cGy). Age was the only significant prognostic factor identified (P less than 0.01). The 5-year survival rates were 76% for adults and 14% for children. All 14 patients who died had recurrent or residual tumor at the primary site. This review suggests that in patients with primary posterior fossa ependymomas the following is true: 1) the young patient (5 yr old or younger) has a poor prognosis; 2) there was a trend toward a better 5-year survival rate with a gross total resection; 3) if recurrence occurs, it will be at the primary intracranial site; and 4) symptomatic spinal seeding does not occur frequently. PMID- 1876244 TI - The prognostic significance of postoperative residual tumor in ependymoma. AB - Between 1970 and 1989, 29 patients with intracranial ependymomas were evaluated and treated at the Children's Hospital in Boston. With a median follow-up of 82 months, the actuarial survival rates at 5 and 10 years were 61 +/- 10% and 46 +/- 12%, respectively. Anaplastic histological findings were uncommon (2 of 29). Initial postoperative radiotherapy was given to 25 patients, with a median tumor dose of 5360 cGy. With a median time to recurrence of 22 months, local failure (within 2 cm of original enhancing mass) was the predominant pattern of relapse (15 of 16 failures). The presence of radiographic residual disease seen on postoperative magnetic resonance imaging or computed tomographic scans was the most important prognostic variable for patients with intracranial ependymoma. Analysis of the 19 patients who underwent postoperative imaging revealed a 75 +/- 15% 5-year freedom from progressive disease for 9 patients with no residual disease, as compared with 0% freedom from progressive disease for the 10 patients with gross residual disease (P = 0.03). In contrast, the surgical assessment of residual disease was not significant (P = 0.4). Age at presentation was also a significant prognostic factor. The overall actuarial survival rate at 12 years for infants 24 months or younger at diagnosis was 0%, as compared with 62 +/- 13% for older patients (P = 0.03). For non-anaplastic ependymomas, complete surgical resection followed by local-field, high-dose (greater than 54 Gy) radiotherapy appears to offer the greatest chance for long-term survival. Because of the markedly reduced survival rate for patients with radiologically apparent postoperative disease, maximal surgical resection and novel therapeutic endeavors appear warranted for this high-risk group. Future protocols should use postoperative imaging, not operative reports, to stratify patients with ependymoma. PMID- 1876245 TI - Cerebral vasospasm and vasoconstriction caused by endothelin. AB - We investigated the histological changes between arteries constricted by endothelin for 7 days and vasospastic arteries induced by the double injection of autologous blood. Group 1 was a sham-operated group. Group 2 animals received a continuous cisternal injection of endothelin-1 (1.7 x 10(-9) mol/7 days) by a miniosmotic pump implanted in the neck musculature for 7 days. Group 3 received double injections of cisternal blood administered 48 hours apart. Angiography showed severe constriction of the basilar artery, 34.6% and 43% in Groups 2 and 3, respectively, on Day 7. Histological study showed marked constriction of the basilar artery in both Group 2 and Group 3. Degenerative changes in endothelial cells and smooth muscle cells were observed in both Group 2 and Group 3. Immunohistochemical study demonstrated endothelin-1 in the endothelial cells in Group 2, but not in Group 1 or in Group 3. It is suggested that endothelin-1 may play an important role in the pathogenesis of cerebral vasospasm. PMID- 1876246 TI - Cervical spondylotic myelopathy: treatment with posterior decompression and Luque rectangle bone fusion. AB - Cervical spondylotic myelopathy appears to result from a combination of factors. The two major components are 1) compressive forces resulting from narrowing of the spinal canal, and 2) dynamic forces owing to mobility of the cervical spine. There is substantial evidence to suggest that the repetitive trauma to the spinal cord that is sustained with movement in a spondylotic canal may be a major cause of progressive myelopathy. Utilization of extensive anterior procedures that remove the diseased ventral features as well as eliminate the dynamic forces owing to the accompanying fusion have grown in popularity. Cervical laminectomy enlarges the spinal canal, but does not reduce the dynamic forces affecting the spinal cord, and may actually increase cervical mobility, leading to a perpetuation of the myelopathy. The authors propose the combination of posterior decompression and Luque rectangle bone fusion to deal with both the compressive and the dynamic factors that lead to cervical spondylotic myelopathy. Ten patients who had advanced myelopathy underwent the combined procedures. Nine of the 10 experienced significant neurological improvement, and the 10th has had no progression. The combination of posterior decompression and Luque rectangle bone fusion may offer a simple, safe, and effective alternative treatment for cervical spondylotic myelopathy. PMID- 1876247 TI - Use of intrathecally administered morphine in the treatment of postoperative pain after lumbar spinal surgery: a prospective, double-blind, placebo-controlled study. AB - Improved control of postoperative pain is now known to reduce the incidence of morbidity. Although spinally administered narcotics have found a clear role in chest and abdominal surgery, their role in lumbar spinal surgery is debated. We conducted a prospective, double-blind, randomized, placebo-controlled trial of intrathecally administered morphine sulfate after lumbar spinal surgery in 56 patients. Patients received 0, 0.125, 0.25, or 0.5 mg of intrathecally administered morphine during extradural lumbar spinal operations, and the effects on postoperative analog pain scores, narcotic consumption, complications, and length of hospitalization were assessed. As compared with systemic narcotic administration, intrathecally administered morphine provided superior analgesia in a dose-dependent fashion without an increase in narcotic side effects. Consumption of parenteral narcotics on the first postoperative day and over the total hospitalization period decreased in correlation with increasing doses of intrathecally administered morphine. Mean length of hospitalization was significantly decreased, as compared with the control group, in patients receiving 0.25 or 0.5 mg of intrathecally administered morphine. When proper precautions are observed, intrathecally administered morphine can improve the postoperative care of patients undergoing lumbar spinal surgery. PMID- 1876248 TI - Prevention of an air embolism by moderate hypoventilation during surgery in the sitting position. AB - The effect of ventilation (normo-, hypo-, and hyperventilation) on transverse sinus pressure (TSP), central venous pressure (CVP), mean arterial blood pressure (mABP), and heart rate was studied in 15 patients undergoing neurosurgical treatment in the sitting position for tumors of the posterior fossa, and the findings were compared with the influence of positive end expiratory pressure (PEEP) on these parameters. TSP was not influenced significantly by PEEP ranging from 0 to 15 mbar, whereas CVP increased. At the same time, mABP decreased slightly. In contrast, TSP showed characteristic changes with varying ventilation: during normoventilation [end expiratory CO2 pressure (PECO2), 38 mm Hg], TSP was 3 mm Hg and increased to 7 mm Hg on average with hypoventilation (PECO2, 44 mm Hg), whereas hyperventilation (PECO2, 32 mm Hg) caused a reduction in TSP to the atmospheric range. At the same time, CVP remained unchanged, whereas mABP increased with hypoventilation. Presuming that the risk of venous air embolism is closely related to the level of TSP, our results allow the following conclusions. 1) PEEP does not seem to be effective in preventing venous air embolism. 2) Hyperventilation is dangerous in the sitting position, as TSP is reduced to the atmospheric and even subatmospheric range. 3) To prevent air embolism, moderate hypoventilation is recommended during the most critical period of exposing the posterior fossa followed by normoventilation when surgery of the actual lesion has begun. PMID- 1876249 TI - Intracerebral temperature in neurosurgical patients. AB - Recent laboratory results have indicated that the ischemic brain is very sensitive to minor variations in temperature. This has created new interest in hypothermia and brain temperature. There is, however, very little information available regarding human intracerebral temperature and its relation to body core temperature during normal and pathological circumstances. We therefore made continuous measurements of the temperature of the lateral ventricle in 15 neurosurgical patients utilizing a newly developed technique with copper constantan thermocouples introduced through a plastic catheter also used for monitoring intracranial pressure. The intraventricular temperature was higher than the rectal temperature during approximately 90% of all measurements. The largest temperature gradient measured was 2.3 degrees C. Usually the difference between the temperature of the rectum and the brain was much smaller, the mean value being 0.33 degrees C. For the patients in the most severe condition, the rectal temperature was sufficiently close to the brain temperature to afford a reliable basis for adequate clinical judgment. PMID- 1876250 TI - Telecanthal approach for meningiomas in the ethmoid and sphenoid sinuses. AB - In three cases involving meningiomas in the ethmoid and sphenoid sinuses, transbasal spreading of the interocular distance (telecanthal approach) was used for tumor removal and reconstruction of the skull base. This telecanthal approach involves 1) bilateral en bloc removal of the superior lateral rim of the orbit, the nasal bone, and the posterior lateral wall of the orbit; 2) detachment of the medial canthal ligaments; and 3) spreading of the interocular distance. This approach provides a wide working space beneath the anterior half of the midline skull base, and needs neither a facial incision nor significant retraction of the brain. The surgical technique and its modification are described. The discussion focuses not only on comparisons with other techniques, but on the indications for this approach. Meningiomas originating in the paranasal sinuses are rare; a brief review of the literature concerning the clinicopathological features and pathogenesis is also given. PMID- 1876251 TI - Operative approach to the frontal skull base: extensive transbasal approach. AB - An operative technique called the extensive transbasal approach is reported with the operative results of 11 cases. This is an operative mode in which en bloc osteotomy of the orbital roofs and frontal sinus is performed after ordinary bifrontal craniotomy. Through this approach, a far wider operative space than that afforded by conventional operative techniques is possible, and reconstruction of the frontal base can be made securely. We consider this approach of major clinical value. PMID- 1876252 TI - A shape-corrective shunt-passer using a titanium-nickel alloy. PMID- 1876253 TI - A familial coincidence of pseudotumor cerebri and communicating hydrocephalus. AB - A family in which the mother and two of four daughters had a diagnosis of pseudotumor cerebri and one son developed communicating hydrocephalus is described. The other two daughters both have a long history of headaches but no signs of intracranial hypertension. The argument is advanced that there exists a defect of cerebrospinal fluid absorption common to pseudotumor cerebri and communicating hydrocephalus. PMID- 1876254 TI - Hypertrophic spinal pachymeningitis: report of two cases and review of the literature. AB - The cases of two patients with idiopathic pachymeningitis hypertrophica that caused progressive paraparesis are presented. Gadolinium-enhanced magnetic resonance imaging was used to demonstrate this pathological entity in one patient, and myelography was used in the other. Decompressive surgery led to significant neurological improvement. The etiology, diagnosis, and management of this disease is discussed, and the literature is reviewed. To our knowledge, this is the first report to describe the features of this rare pathological entity on magnetic resonance imaging. PMID- 1876255 TI - The clinical importance of the inferolateral trunk of the internal carotid artery. AB - The inferolateral trunk (ILT) of the internal carotid artery (ICA) is a branch that arises inferiorly from the C4 segment of the cavernous ICA. It provides blood supply to the 3rd, 4th, and 6th cranial nerves, as well as to the gasserian ganglion. The ILT anastomoses to branches of the internal maxillary artery, providing collateral circulation between the external carotid artery and the ICA systems. Retinal and cerebral emboli can arise from the external carotid artery system and travel via the ILT to the ICA. Cranial nerve palsies may result after occlusion of the ILT. We present the cases of four patients who had iatrogenic neurological dysfunction subsequent to intravascular procedures that involved the ILT. These cases provide further clinical confirmation of the importance of this blood vessel. A 5th case involving iatrogenic occlusion of the ILT and no neurological deficit is also presented, demonstrating that the ILT is not the sole blood supply of the cranial nerves in the cavernous sinus. PMID- 1876256 TI - Brain stem abscess treated successfully by medical therapy. AB - A case of a solitary brain stem abscess in a 55-year-old man is presented. The computed tomographic scan and clinical picture allowed the presumptive diagnosis to be made. The abscess resolved completely after treatment with chloramphenicol, vancomycin, and ceftazidime administered intravenously. Medical therapy should be considered as an effective treatment of a brain stem abscess, provided the antibiotic therapy is administered under close clinical and computed tomographic monitoring. PMID- 1876257 TI - Double compartment hydrocephalus in an adult. AB - A case of double-compartment hydrocephalus in an adult is presented. Although this entity is infrequently noted in children, it is diagnosed even more rarely in the adult population. A discussion of the spectrum of abnormal cerebrospinal fluid dynamics of the 4th ventricle and treatment options are presented. PMID- 1876258 TI - Primary intrasellar coccidioidomycosis simulating a pituitary adenoma. AB - The case of a 68-year-old woman who had relatively acute, unilateral ophthalmoplegia is reported. Radiological studies indicated a mass lesion involving the pituitary gland and left cavernous sinus. Pathological tissue obtained by the transsphenoidal approach revealed the presence of a Coccidioides granuloma. This pathological entity should be considered when evaluating patients with a pituitary mass and ophthalmoplegia. PMID- 1876259 TI - Subependymoma with rhabdomyosarcomatous differentiation: report of a case and literature review. AB - A unique gliomesenchymal neoplasm, consisting of a subependymoma, a form of low grade glioma, and a rhabdomyosarcoma, is described. It arose and recurred in the brain stem of a 52-year-old man. Immunohistochemical studies demonstrated the presence of a neuroectodermal marker S-100 protein within some sarcoma cells. The occurrence of this rare tumor supports the concept that striated muscle may derive from a neuroectodermal precursor lesion. PMID- 1876260 TI - Extreme lateral approach to intradural lesions of the cervical spine and foramen magnum. PMID- 1876261 TI - Civilian gunshot wounds to the head. PMID- 1876262 TI - Reactions of cell structures of the brain of laboratory animals to oxygen insufficiency. PMID- 1876263 TI - Method for identifying adrenergic nervous elements by the glyoxylic method using pontamine sky blue. PMID- 1876264 TI - Interhemispheric asymmetry of the interaction of transcallosal and ascending flows of excitation in the visual cortex of the cat. AB - Interhemispheric interrelationships under conditions of the combination of transcallosal stimulation and monocular photostimulation with varied time intervals have been studied in acute experiments on 20 curarized cats with topographic recording of evoked potentials (EP) from homotypical areas of the visual cortex of both hemispheres. Interhemispheric asymmetry was established in the amplitude-temporal parameters of the visual and transcallosal EP, as well as of the resulting EP in the entire range of lags between the heteromodal stimuli. The asymmetry of the viral EP was greatest in magnitude, the asymmetry of the transcallosal EP was medium in magnitude, and the minimal magnitude was that of the visual EP with photostimulation the contralateral eye. With the combination of transcallosal and visual stimulation, dynamics were found of the magnitude of the resulting EP which reaches a maximum of the magnitude and has a monohemispheric directivity in conditions of the model experiments which correspond to the most natural conditions of the transcallosal interrelationship of the hemispheres. It is hypothesized that the transcallosal interrelationship is an important factor of the formation of the relative specialization of the cerebral hemispheres. PMID- 1876265 TI - Influence of brain stem structures on the formation of the defensive behavior of animals. AB - The dependence of the dominant form of the defensive behavior of white male mongrel rats on the functional state of the brain stem inhibitory locomotor system has been studied in chronic experiments. It was established that the electrolytic destruction of the inhibitory zones of the cuneate nucleus of the midbrain, the medial parabrachial nucleus, the central and great nuclei of the raphe leads to the dominance of active defensive reactions in animals in confrontations with partners. The opposite effect is exerted by local injection of kainic acid into these regions of the brainstem. It is hypothesized that the functional state of the brain stem inhibitory locomotor system can exert a modulating influence on the formation of the defensive behavior of animals. PMID- 1876266 TI - Participation of cholinergic mechanisms in the origination of the dendritic potential of the cerebral cortex. AB - The influence of a series of muscarinic (M) and nicotinic (N) substances on the dendritic potentials of the cerebral cortex was studied in acute experiments on adult cats under deep nembutal anesthesia. M-Antagonists in large doses and M agonists, N-agonists and acetylcholine elicited a decrease in the amplitude of dendritic potentials. M-Antagonists in small doses and N-antagonists elicited an increase in the amplitude of the dendritic potentials. The application of an anticholinesterase substance, proserine, to the cortex elicited an increase in the amplitude and duration of the dendritic potentials. It is hypothesized that there are postsynaptic M-cholinoreceptors of the M1 type, presynaptic M cholinoreceptors of the M2 type, and presynaptic N-cholinoreceptors in the neuropil of layer I of the cortex. PMID- 1876267 TI - Responses of frog vestibular neurons to combined temperature microstimulation of the semicircular canals. AB - The temperature microstimulation of the semicircular canal (heat bursts lasting about 2 sec with a peak amplitude of 0.5-5.0 degrees C) can be regarded as an analog of angular acceleration acting within the cavity of the given canal; the combination of temperature microstimulations targeted simultaneously on several canals can serve as a physical model of accelerated rotation having complex spatial characteristics. The recording of the activity of neurons of the vestibular nuclei of the frog (n = 278) in response to temperature microstimulation of the canals showed that 80% of the neurons have inputs from one to two canals and only 20% from three to six canals. The distribution of laterality was characterized by the predominance of ipsilateral inputs: 201 neurons (72.3%) had only ipsilateral inputs; 14 neurons (5%) had only contralateral inputs; 63 neurons (22.7%) had both inputs. The ipsilateral horizontal (67.6%) and the posterior (61.9%) were the most effective inputs; while among the contralateral, the posterior (21.2%) canals were the most effective; the least effective were the contralateral horizontal (8.6%) and the anterior (5.0%) canals. The presence of latent canal inputs (both excitatory and inhibitory) which showed up in combination with effective inputs was demonstrated. PMID- 1876268 TI - Influence of pineal peptides on the dynamics of the circadian and minute motor biorhythms in rats. AB - A peptide preparation of the pineal, epithalamin, when administered chronically, exerts a modulating influence on the diurnal fluctuations of the motoric activity of rats. It also decreases the amplitude of apomorphine stereotypy and induces a restructuring of a modulatory character in its rhythmic structure. It is hypothesized that the pineal peptides participate in the maintenance of homeostasis by means of the stabilization of rhythmic processes of various periods. PMID- 1876269 TI - Parasympathetic control of the spontaneous defibrillation of the heart ventricles in animals of various ages. AB - The role of the parasympatetic division of the nervous system in the process of the spontaneous defibrillation of the heart ventricles in guinea pigs of various ages has been investigated. It was shown that the intensification of parasympathetic control in newborn and sexually mature animals by means of the stimulation of the vagus nerves through the administration of acetylcholine leads to an increase in the duration of ventricular fibrillation, while in old animals this leads to the possibility of its prevention. The important role of the maintenance of sympathetic control in the mechanisms of the recovery of normal cardiac rhythm has been demonstrated. PMID- 1876270 TI - Neurophysiological and pathomorphological features of the development of alcoholism (experimental investigation). PMID- 1876271 TI - Neurophysiological mechanisms of the attention disturbance in children with learning difficulties. AB - The features of orientation reaction (OR) and the background EEG were investigated with the purpose of studying the neurophysiological mechanisms of the disturbance of voluntary attention in children aged 6.5-9 years with learning difficulties caused by delayed mental development (DMD). A decrease in the expressivity of components of the OR as compared with the norm, discovered in a situation of involuntary attention against a background of insufficiently developed cortical rhythmicity in the alpha range, was compensated for given an increase in the significance of the stimuli. These facts support the hypothesis of a deficit in regulatory corticofugal influences in children with DMD. The inadequacy of the engagement of central regions of the cortex characteristic of children with DMD in the realization of OR in a situation of directed attention can be regarded as a reflection of disturbances of the integrative activity of the brain. PMID- 1876272 TI - Capacity of bottle-nosed dolphins for generalization based on a relative sign. AB - Using a new modification of a previously proposed method in the bottle-nosed dolphin, a conditioned reflex was developed and consolidated to a relative spatial sign, namely the choice always of the left out of two identical objects under conditions of constant change of the position of this pair of stimuli against the background of one of the sides of the pen. The specialization was checked by means of the presentation of the pair of stimuli through various changes of the surrounding setting, including the discordance of external landmarks, as well as by the means of the presentation of the stimuli. Then the objects were replaced by others (12 pairs of stimuli) sharply differing from the initial stimuli in form, size, material, etc. The maintenance of appropriate choice, including with change in the medium of presentation of the stimuli) attested to the capacity of the dolphins to abstract and generalize on the basis of a relative sign, i.e., of abstraction and generalization in the "to the left to the right in general" choice of two objects. PMID- 1876273 TI - Interrelationships of the emotionally positive and negative regions of the brain of the edible snail. AB - The changes in the behavior of the garden snail during self-stimulation through electrodes chronically implanted in specific regions of the brain are described in this study. The stimulation of the mesocerebral region led to an increase in the frequency of reinforced behavior, whereas stimulation of the rostral portion of the parietal ganglia led to a decrease in the frequency of reinforced behavior. An inference is reached regarding the emotional coloration of the effects of the stimulation of these regions. The interrelationships of the neurons located in the mesocerebrum and the parietal ganglia were studied in neurophysiologic experiments. It was found that the activation of the cells of the mesocerebrum inhibits the spontaneous activity of the serotoninergic cells of the pedal ganglia which sensitize the defensive reactions of the snail, and simultaneosly attenuate the sensory input of the command neurons of defensive behavior, which leads to the effective inhibition of the defensive reactions that is necessary during the activation of sexual behavior. PMID- 1876274 TI - Reactions of neurons of the somatosensory cortex of the rabbit to nociceptive stimuli of varying genesis. PMID- 1876275 TI - Role of the basal ganglia in the reproduction of instrumental reactions developed in response to electrostimulation of the hippocampus. AB - A defensive instrumental conditioned reflex (CR) successively to light flashes and to electrostimulation of the dorsal hippocampus (DH) and the caudate nucleus (CN) was developed in dogs with electrodes implanted in the brain. The contralateral of the DH, CN, the accumbent nucleus (AN) and the globus pallidus (GP) were tested for reproducibility of the instrumental movement. In a second series, the percent of evoked movements was compared with the EP arising in response to signal and test stimulation. The degree of participation of the tested structures in the motivational, signal, and executive components of the CR was elucidated. In the first series the movements were practically not reproduced. In the second series, in the presence of connections from the signal to the tested structures, they were elicited only by stimulation of the AN (15%). In the same series, given bilateral connections, movements in response to the stimulation of the basal ganglia occurred somewhat more frequently (up to 28%). The stimulation of the contralateral DH elicited movements in 75-100% of cases. When stimulation of the CN became a signal, the stimulation of the AN and the GP was accompanied in 40-100% of cases by movement. Thus, the AN participates to a minimal degree in the executive component of the CR. Participation of the basal ganglia in the signal component of the CR was greatest in the third series, which indicates that intrasystemic generalization is more effective than intersystemic. PMID- 1876276 TI - Role of gamma-aminobutyric acid in the inhibitory effect of emotional stress on the sexual activity of mice. PMID- 1876277 TI - Hypothalamic monoamines in the postnatal ontogenesis of rats. PMID- 1876278 TI - User-pay for hospital services. PMID- 1876279 TI - A survey of available beds in area health boards: 1976-1991. AB - The last few years has been a period of great change for the health service. A survey was undertaken to examine trends between 1976 and 1991 in the number of available beds within area health boards. Data collection included a survey of area health boards. The survey found that between 1976 and 1991 available beds decreased by 31.0%. However, most of the decrease occurred over the last 3 years; between 1988 and 1991 bed numbers decreased by 18.5%. PMID- 1876280 TI - Alkylating agents and purine analogues in primary glomerulonephritis with nephrotic syndrome. PMID- 1876281 TI - Primary hyperlipidaemia is not associated with increased urinary albumin excretion. AB - In a group of 141 otherwise healthy subjects attending a lipoprotein clinic, urinary albumin excretion was measured to determine whether primary hyperlipidaemia was associated with evidence of early renal dysfunction. There was no evidence of increased urinary albumin concentrations or albumin:creatinine ratios when compared with data for normal controls. There were no differences in these parameters when the values for the upper and lower quartiles of the cholesterol distribution were compared, and no relationship existed between plasma cholesterol and albuminuria. A weak association was shown between plasma triglyceride and urinary albumin concentration after log transformation of the data. We conclude that hyperlipidaemia per se is not associated with renal disease as measured by sensitive assays of albuminuria. PMID- 1876282 TI - Effect of two regimens of intravenous amino acid infusion on renal haemodynamics, renal tubular function and sodium and water homeostatic hormones in healthy humans. AB - The effect of two different regimens of intravenous infusion of amino acids on glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium and water handling judged from the clearance of lithium (CLi), and plasma concentrations of angiotensin II (Ang II), aldosterone (Aldo), arginine vasopressin (AVP), atrial natriuretic peptide (ANP), growth hormone (GH), and glucagon was investigated in healthy humans. In the first protocol (n = 11) the infusion lasted 90 min; both GFR and RPF increased significantly (median increase 7.1% and 9.1% respectively, P less than 0.05 both). In the second protocol (n = 13) the infusion lasted 30 min; both GFR and RPF tended to increase (median increase 3.5% and 7.4%) but the change did not reach significance. The changes in tubular sodium and water handling were similar in the two protocols. Absolute reabsorption rates in the proximal tubules were unaltered, resulting in an increased output into the distal tubules that was totally compensated for by an increased distal reabsorption. Thus no changes in urinary excretion of sodium and water were observed. Ang II, Aldo, AVP, ANP and GH were unchanged by amino acid infusion, but glucagon increased. It is suggested that the alterations in renal haemodynamics and distal tubular reabsorption may be mediated by glucagon. PMID- 1876283 TI - Control of hypertension by verapamil enhances renal damage in a rat remnant kidney model. AB - The effect of calcium channel blockers on the progression of renal failure is controversial. In contrast with earlier studies, we recently reported that moderately large doses of verapamil significantly accelerated chronic renal failure in the rat remnant kidney model. Studies reporting beneficial effects of verapamil were characterised by a much lower dose of verapamil and by the start of treatment immediately after renal ablation, which potentially interfered with the initial phase of remnant kidney hypertrophy. We therefore studied the effects of a high, fully antihypertensive oral dose of verapamil (100-150 mg/kg/per day; group Vera high) and a low, haemodynamically almost ineffective dose (10-15 mg/kg per day; group Vera low), on the progression of chronic renal failure in female Wistar rats with 5/6 nephrectomy. The treatment was started no earlier than 5 weeks after renal ablation, and matched groups of 20 animals were followed for 16 weeks thereafter. High-dose verapamil reduced systolic blood pressure to median values of 130-140 mmHg throughout the experimental period, whereas blood pressure in Vera low animals remained elevated at median values of 165-172 mmHg similar to non-treated rats with 172-185 mmHg median systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876284 TI - Comparison of blood biocompatibility during haemodialysis with cuprophane and polyacrylonitrile membranes. AB - Clotting within the dialyser is one of the most significant clinical parameters of biocompatibility. A study was designed to evaluate the biocompatibility of two different dialysis membranes (cuprophane and polyacrylonitrile) during therapy with conventional heparin. Transient leukopenia during cuprophane but not during polyacrylonitrile haemodialysis was observed, and elastase release using polyacryonitrile membranes was reduced (P less than 0.001). An elevation in F VIII:C activity during cuprophane haemodialysis has to be taken as an indication of endothelial disturbances. There was a significant (P less than 0.001) platelet activation (beta-thromboglobulin) and combined thrombin/plasmin generation using cuprophane membranes. This new synthetic polyacrylonitrile membrane inactivates the clotting in an extracorporeal system to a sufficient degree and allows a reduction in dosages of heparin. Platelet activation, platelet turnover, disturbances of endothelium, fibrinolysis activation, and granulocyte activation are reproducible parameters of a described interaction model. They also permit a comparison of different haemodialysis membranes. PMID- 1876285 TI - Tumour necrosis factor does not increase during routine cuprophane haemodialysis in healthy well-nourished patients. AB - Serum tumour necrosis factor (TNF) was measured by both bioassay and immunoassay (ELISA) during routine cuprophane acetate haemodialysis in 17 asymptomatic patients. In 14 (82%) there was no change in the serum values during haemodialysis. TNF was found to increase, using both assays, in three patients, the responders. These patients differed from the others in terms of body mass index, mean index 16.8 kg/m2 (range 14.8-18.2), compared to the non-responders, mean 24.1 kg/m2 (range 19.6-33.1), P less than 0.05, and had an increased serum calcium, mean 2.9 mmol/l (range 2.6-3.2) compared to the non-responders, mean 2.4 mmol/l (range 1.7-2.8), P less than 0.05. Two of the TNF responders subsequently died of cachexia and respiratory infection. The third underwent a successful parathyroidectomy, and when retested after an increase in body-weight with a normal serum calcium concentration no longer showed an increase in TNF during haemodialysis. PMID- 1876286 TI - The effect of vitamin C intake on plasma oxalate in patients on regular haemodialysis. AB - Plasma oxalate was measured on two occasions in 18 patients with end-stage renal failure on regular haemodialysis treatment: once while on a routine dose of vitamin C (100 mg/day) and subsequently after 2 weeks administration of a larger dose of vitamin C (500 mg/day). Pre- and post-dialysis concentrations were all markedly increased, reflecting the reduced glomerular filtration rate of end stage renal failure. Both pre- and post-dialysis oxalate increased significantly following the increase in ascorbate dose but there was no significant correlation between plasma oxalate and ascorbate results. Considerations governing dosage of vitamin C in patients with chronic renal failure are discussed. PMID- 1876287 TI - Comparison of survival in continuous ambulatory peritoneal dialysis and hospital haemodialysis: a multicentric study. AB - We compared the survival of 842 patients on centre haemodialysis to 272 patients on continuous ambulatory peritoneal dialysis (CAPD). All patients selected had begun treatment between 1 January 1984 and 30 June 1988 and were from six centres which participate in a regional renal patients registry. Patients on CAPD were older and had a greater proportion of diabetes and other associated diseases. Age, diabetes, and cardiovascular diseases were associated with a shorter survival on treatment in all the patients studied. Without adjustment for risk factors, patient 3-year survival was higher in centre haemodialysis than in CAPD, 80% versus 64% respectively. However, no significant differences could be shown in the survival rates of the two treatment modalities after accounting for the heterogeneity of the patients in the two groups, either by stratification or by multivariate analysis (Cox). Age was the main predictive factor for CAPD patient survival, while the influence of diabetes and cardiovascular diseases was less clear. Technique survival was much better in centre haemodialysis (94% versus 56% in CAPD, 3-year survival). Older age and diabetes mellitus were associated with a greater risk of switching from centre haemodialysis to CAPD and a trend to retain those patients on CAPD. PMID- 1876288 TI - Correction of anaemia with recombinant human erythropoietin despite low serum ferritin. PMID- 1876289 TI - Causes and treatment of infertility. PMID- 1876290 TI - Fertility services at the Chiltern. PMID- 1876291 TI - Depression and diet. PMID- 1876292 TI - Managing arterial ulcers. PMID- 1876293 TI - Exploring a medical phenomenon. PMID- 1876294 TI - The future need not be baby-bound. PMID- 1876295 TI - Critical incident analysis. PMID- 1876296 TI - 'Angels of Death' cause sensation in Austrian courts. PMID- 1876297 TI - RMNs have a part to play. PMID- 1876298 TI - Whose body is it anyway? PMID- 1876300 TI - Substance abuse. The last resort. PMID- 1876299 TI - Substance abuse. A problem for society? PMID- 1876301 TI - New needles for old. PMID- 1876302 TI - EUSOL: there'll be no eulogy. PMID- 1876303 TI - Your wound care questions answered. PMID- 1876304 TI - Wound care. Nurses: the weak link. PMID- 1876305 TI - Midwifery. Developing counselling skills. PMID- 1876306 TI - Why the UK needs nurse anaesthetists. PMID- 1876307 TI - From practice to theory. PMID- 1876308 TI - Planning informed nursing care. PMID- 1876309 TI - In touch with reality. PMID- 1876310 TI - Drug addict--not me! PMID- 1876311 TI - Pneumatoceles and pneumothorax in Pneumocystis carinii pneumonia. PMID- 1876312 TI - Kaizen, the changing face of health care. PMID- 1876313 TI - Coronary artery bypass grafting. The relationship of surgical volume, hospital location, and outcome. AB - The relationship between mortality, surgical volume, and location was investigated in the university medical centers (UMCs) in the Greater New York metropolitan area for patients undergoing coronary artery bypass grafting (CABG) in 1986. Three high-volume and five low-volume institutions, with a total of 49 surgeons, performed a total of 3,408 CABG operations. The crude mortality rates were 4% for simple, 14.7% for complex, and 5.3% combined for all UMC CABG operations. The crude mortality rates for CABG operations in high- and low-volume centers were respectively 3.6% and 4.8% for simple and 16.1% and 11.3% for complex operations. No statistically significant differences between urban (N = 6), suburban (N = 2), high-volume (N = 3), or low-volume (N = 5) centers or physicians were found (all p values greater than 0.05). Taken together, these findings suggest that surgical volume and location are not significant factors for predicting outcome for CABG. PMID- 1876314 TI - Optimal therapy of cryptococcosis in patients with the acquired immunodeficiency syndrome. AB - Although amphotericin B (AB) is the primary therapeutic agent for cryptococcosis complicating the acquired immunodeficiency syndrome (AIDS), the total dose administered is extremely variable, and the end point of therapy has not been well defined. Since these patients require life-long suppressive therapy following the primary therapy, the definition of treatment "end point" becomes crucial. To delineate more effective treatment approaches, we reviewed the medical records of 48 patients with cryptococcosis complicating AIDS. Fever (81%) and headache (77%) were the predominant symptoms. A clinical response to AB (defervescence and resolution of symptoms) was noted in 46% of the febrile patients. The cumulative AB dose administered to the time of clinical response was variable (0.1-1.76 g), but was noted early in the majority of the patients (less than 0.4 g). Repeat fungal cultures from the initial positive site for Cryptococcus neoformans (CN), obtained after observation of the clinical response, were negative in 7/7 patients. Nosocomial bacterial infections were quite common and often complicated intravenous AB therapy. Bacteremias were documented in 10/14 febrile episodes occurring during AB therapy in the 22 patients with an initial clinical response. Bacteremias were identified in 6/21 patients who failed to defervesce with AB therapy. Staphylococcus aureus (N = 9) and Salmonella species (N = 2) were the most common pathogens causing bacteremia. An algorithm for the treatment of cryptococcosis complicating AIDS may shorten the duration of primary intravenous AB therapy. This might reduce secondary infectious complications and the costs of hospitalization. PMID- 1876315 TI - Mary Edwards Walker, MD: the only woman ever awarded the Congressional Medal of Honor. PMID- 1876316 TI - Artificial neural networks: one step too far? PMID- 1876317 TI - Contrasting attitudes in the evolution of surgery for treating ulcerative colitis and Crohn's disease. PMID- 1876318 TI - Pneumatoceles. PMID- 1876319 TI - Traumatic thrombosis of a vertebral artery in a hypoplastic vertebrobasilar system. Protective effect of collateral circulation. PMID- 1876320 TI - Left paraduodenal hernia. PMID- 1876321 TI - Increased lead absorption in a potter and her family members. PMID- 1876322 TI - Requirement that prescriber's name be imprinted or stamped on prescription forms. PMID- 1876323 TI - Incidence of high-level gentamicin resistance among enterococci isolated from blood cultures in a community hospital in New York. PMID- 1876324 TI - The research-practice relationship. Commentary and response. PMID- 1876325 TI - Movement and time: exertion and perceived duration. AB - This study examined differences in consciousness indexes (perceived duration of time) at different levels of physical exertion within the framework of Newman's model of health and with emphasis on Prigogine's theory of dissipative structures. The sample consisted of 100 volunteers participating in regular aerobic exercise. Instruments included 817E Monarch Stationary Bicycles, 1800 Dynamap Automatic Blood Pressure/Pulse Monitors, the production method of time estimation, and the Perceived Exertion Scale. Repeated measures ANOVA revealed significant differences in consciousness indexes during exertion (p less than .00001). Paired t-tests yielded significant differences between the resting consciousness index and consciousness indexes at preferred, increased, and decreased exertion levels (p = .000). Results indicate that the consciousness index decreased with physical exertion regardless of actual exertion level. In addition, changes in perceived exertion and in physiological parameters suggest a pattern of expanding consciousness that is consistent with the theoretical framework. PMID- 1876326 TI - The lived experience of health in the oldest old: a phenomenological study. AB - In the United States and in many other parts of the world, the fastest growing age group is 80 years and over. It is precisely in this oldest old age cohort that very little is known about the experience of health. The purpose of this study was to investigate the lived experience of health for the oldest old within the community through the use of the phenomenological method. While there has been some research on the personal experience of health, the meaning of these experiences has not been studied in the oldest old, community dwelling elderly. Findings reveal that for this age group, health is an abiding vitality emanating through moments of rhapsodic reverie in generating fulfillment. There are many implications for further research and practice based on the meaning of health as described by the oldest old. PMID- 1876327 TI - Cultural care: the missing link in severe sensory alteration. AB - The phenomenon of severe sensory alteration has been studied for some twenty-five years. Sensory overload, sensory deprivation, and sleep deprivation have been identified as contributing factors in its cause. Yet, the incidence of severe sensory alteration remains high. In this paper the author suggests that Leininger's theory of cultural care advocating the use of culturally assistive, supportive, or facilitative acts in nursing care, may provide important new insights into this phenomenon. PMID- 1876328 TI - Struggling with going along when you do not believe. AB - The phenomenon central to this study is, "struggling with going along in a situation you do not believe in." It emerged as a predominant universal lived experience within the lives of outstanding nurses in the United States studied earlier by the author. The purpose of the research reported in this article was to generate a structure of the lived experience of "struggling with going along in a situation you do not believe in," using Parse's research methodology. Through the processes of the method: participant selection, dialogical engagement, extraction-synthesis and heuristic interpretation, a structure of the lived experience for persons over 65 years of age was generated. This structure is: struggling with going along in a situation you do not believe in is justifiable yielding, as opposing views intensify personal convictions and compel disclosure while suffering consequences. When linked with the major concepts of Parse's theory, the theoretical definition is: valuing the powering of revealing concealing. Recommendations for further study are offered. PMID- 1876329 TI - A Rogerian theoretical tapestry. AB - A five-level analytical framework is employed in order to critically analyze Martha E. Rogers' science of unitary human beings. Philosophical and epistemological threads are followed in an attempt to evaluate the coherence and comprehensiveness of her theoretical work. The interconnectedness between the five levels is demonstrated, and areas of debate and concern are elucidated. The philosophical and epistemological tapestry emerging from Rogers' theoretical thinking is found to reflect coherence in her philosophical and epistemological positions and beauty in the pattern found therein. The challenge lies in finding innovative methods of inquiry congruent with Rogers' view. PMID- 1876331 TI - Nursing theory 25 years later. PMID- 1876330 TI - Mysteries of health and healing: two perspectives. PMID- 1876332 TI - Chaos in nursing research. PMID- 1876333 TI - Evaluating nursing theory-based practice. PMID- 1876334 TI - Surgical correction of the Wolff-Parkinson-White syndrome. AB - The results of corrective surgery in 75 consecutive patients with Wolff-Parkinson White (WPW) syndrome are reported. There were 47 male and 28 female patients with a median age of 27 years. Intraoperative mapping disclosed 88 accessory pathways, of which 83 were successfully divided at the primary operation without mortality. Two patients underwent successful reoperation at three days and two years respectively. Patient success rates were 93% and 96% for first and total operations. Complications, usually minor, occurred in 20 patients, including permanent pacemaker implantation in two. Surgical correction of WPW syndrome is recommended as a safe alternative to lifelong medical treatment. PMID- 1876335 TI - Duodenal ulcer relapse after eradication of Helicobacter pylori. AB - Thirty-six patients with healed duodenal ulcers, 27 infected with Helicobacter pylori and nine uninfected, were followed for up to 12 months to determine the rate of ulcer relapse. Eight patients withdrew over the follow up period. At one year, 15 of 20 (75%) infected patients and one of eight (13%) uninfected patients had relapsed, p less than 0.05. Eradication of H pylori favourably influences the natural history of duodenal ulcer recurrence. Significant patient morbidity may be prevented by using measures to eradicate H pylori during or after duodenal ulcer healing. PMID- 1876336 TI - Recent advances in retinal surgery. PMID- 1876337 TI - Murine typhus in Kaukapakapa? AB - We report a patient who had not been outside New Zealand with a fever and maculopapular rash. Serology suggested acute murine typhus due to R typhi. This is the first reported case in New Zealand from a nontraveller. PMID- 1876338 TI - Haemophilus influenzae type b cellulitis. AB - Five cases of cellulitis due to H influenzae type b in children are described. Cellulitis due to H influenzae type b should be treated in hospital using parenteral antibiotics in appropriate dosage to cross the blood brain barrier; it is recommended a lumbar puncture is performed in all cases of cellulitis in under two year olds, both to exclude meningitis and to allow the giving of steroids immediately prior to starting the first dose of antibiotics. Index cases and close contacts should be offered chemoprophylaxis to prevent spread of the organism. It seems likely that a vaccine against H influenzae b, effective in under two year olds, will become available in the next few years. PMID- 1876339 TI - Instillation of scolicidal agents into hepatic hydatid cysts: can it any longer be justified? PMID- 1876340 TI - Where have all the doctors gone? (2). Intraurban trends: changes in the geographic distribution of general practitioners in Auckland, 1980-7. AB - During the 1980s the Auckland metropolitan area increased its share of all general practitioners in New Zealand at a much faster rate than its share of the population, resulting in a high level of availability by 1987. In the light of such trends, neoclassical theory would predict a diffusion of general practitioners into areas with fewer doctors where there is less competition for patients. Data for 1980-7, however, indicates that for every FTE general practitioner who located in doctor poor areas of the city, 1.87 general practitioners continued to open practices in areas already well provided for. Or, for every extra consultation that took place in low income suburbs, 1.51 extra consultations occurred in more affluent localities. These results do not provide strong support for a market led diffusion of doctors into areas of need and any gains in increased equity appear to have been achieved at the expense of considerable inefficiency given the likely presence of induced demand. PMID- 1876341 TI - Reflections on carcinoma in situ. PMID- 1876342 TI - The Medical Council and ethics. PMID- 1876343 TI - Water fluoride and fractures. PMID- 1876344 TI - High risk children with deafness. PMID- 1876345 TI - Acute aortic dissection and thrombolysis. PMID- 1876347 TI - Transcervical resection of endometrium--a reason for caution. PMID- 1876346 TI - Giardiasis and municipal water supply. PMID- 1876348 TI - Health reforms: what do they mean for nurses and patients? PMID- 1876349 TI - Still smiling after all these years. Interview by Lyndon Keene. PMID- 1876350 TI - Immunisation. PMID- 1876351 TI - How well is my career? PMID- 1876352 TI - Nursing education: development with purpose. PMID- 1876353 TI - Management of antenatally diagnosed fetal ovarian cysts. AB - 1. Fetal ovarian cysts are usually unilateral, diagnosed in the third trimester and are uncommon. 2. Average ovarian cyst size is 5 x 5 cm at diagnosis and size does not change throughout the pregnancy. 3. Most cysts are functional in origin and histologically benign, simple cysts. 4. Polyhydramnios is a common finding but associated anomalies are rare. 5. Although large cysts can compress other viscera and torsion or rupture can occur, in utero aspiration has limited value in prenatal management. 6. Vaginal delivery with confirmed fetal pulmonary maturity or at term is appropriate. 7. Soft tissue dystocia is rare. Cesarean delivery should be reserved for obstetrical indications only. 8. The best predictor of neonatal cyst torsion risk is length of the cyst pedicle rather than cyst size. 9. When surgery is indicated a cystectomy, with preservation of maximal ovarian tissue is to be preferred over oophorectomy. 10. Ultrasound guided aspiration of neonatal ovarian cysts may be an alternative to surgical management. PMID- 1876354 TI - Postpartum ovarian vein thrombophlebitis: a review. PMID- 1876355 TI - Maternal positions during labor. PMID- 1876356 TI - Vaginal bleeding in premenarchal girls: a review. AB - Vaginal bleeding in childhood is not a common complaint. Serious medical or sociological problems can underly this irregular symptom in young girls. Therefore it requires careful medical investigation followed by appropriate sociologic and psychologic support. The variable etiologies of vulvovaginitis are the most common causes of vaginal bleeding during the prepubertal period. External blood loss can be related to trauma or urologic factors. It can be the presenting sign of relatively rare benign and malignant neoplasms of the genital tract. Precocious menstruation in itself or as a part of precocious puberty must be suspected in these cases. Vaginal bleeding in prepubertal girls is uncommon but warrants careful evaluation because of the special status of the young patient. PMID- 1876357 TI - Heart rate patterns in fetuses exposed to cocaine. AB - Heart rate patterns of 42 fetuses exposed to cocaine near the time of delivery were compared with patterns in 42 controls. Decreased long-term variability and an increased frequency of contractions were observed more often in the cocaine group (P = .046 and P = .0306, respectively). There were no significant differences in the frequency of fetal tachycardia or decelerations. Although accelerations were less frequent in cocaine-exposed fetuses, the difference compared with controls was not statistically significant. We found no characteristic heart rate pattern in fetuses exposed to cocaine near delivery. The heart rate patterns likely represent the underlying state of fetal oxygenation. Frequent contractions in an unstimulated labor should raise suspicions of maternal cocaine use. PMID- 1876358 TI - The relationship between recent cocaine use and pregnancy outcome. AB - We conducted urine screening for cocaine metabolite in 500 consecutive women admitted to a labor and delivery unit. The pregnancy outcome of 411 of the women was determined at that admission. The prevalence of cocaine-positive urines was 15.3% (95% confidence interval 11.8-18.8%). A subset of this population that had not received prenatal care had a prevalence of 62% (95% confidence interval 47.2 76.6%). Women with positive urines were almost four times more likely to have preterm labor and over twice as likely to deliver a premature infant or one with a 1-minute Apgar score of 6 or lower. Our findings support the concept that urine drug screening for cocaine and/or other drugs of abuse should be considered in patients who present with no prenatal care, premature labor, premature delivery, and delivery of an infant with a 1-minute Apgar score of 6 or less. This strategy may enable us to identify and bring to therapy a population of women that could potentially go unrecognized. PMID- 1876359 TI - Heart rate as a predictor of first-trimester spontaneous abortion after ultrasound-proven viability. AB - To discover whether first-trimester spontaneous abortion can be predicted by embryonic heart rate (EHR), we performed a cross-sectional study during the first trimester of pregnancy using high-frequency transvaginal sonography combined with pulsed Doppler. Heart rate was measured in 603 embryos; of these, 580 continued beyond 13 weeks' gestation and 23 ended in first-trimester spontaneous abortion. Based on the continuing pregnancies, we constructed and compared EHR nomograms relating to gestational age, mean diameter of the gestational sac, and crown-rump length (CRL). Embryonic heart rate correlated best with CRL (r = 0.87), and the correlation was best described by a second-degree polynomial regression equation. The mean EHR increased progressively from 110 beats per minute (bpm) at CRL of 3 4 mm to 171-178 bpm at CRL 15-32 mm. At CRL greater than 32 mm, the EHR remained stable at a mean of 170 bpm. The EHRs of the 23 embryos that spontaneously aborted in the first trimester were evaluated according to these nomograms. In 15 cases, the EHR fell outside the 95% confidence interval for CRL (sensitivity 65%), but it was within normal limits in eight (false-negative rate 35%). In ten embryos for which pregnancy continued beyond 13 weeks, the EHR fell outside the 95% confidence interval (specificity 98%, false-positive rate 2%). Our findings suggest that EHR measurements in early pregnancy may be useful in the prediction of first-trimester spontaneous abortion after ultrasound-proven viability. PMID- 1876360 TI - Multifetal reduction of triplets and pregnancy outcome. AB - Multifetal pregnancy reduction has been suggested as a strategy to improve pregnancy outcome in grand multiple gestations of three or more fetuses. We prospectively investigated multifetal pregnancy reduction in 13 women with triplet pregnancies in the first trimester following ovulation induction, in vitro fertilization, or gamete intrafallopian transfer procedures. Eleven women whose triplet pregnancies followed similar reproductive technologies and who declined or were not offered the procedure were managed expectantly. Mean (+/- standard deviation) infant birth weight was 2227 +/- 478 g in the multifetal reduction group and 2239 +/- 399 g in the group managed expectantly. Gestational age was 35.5 +/- 2.3 weeks in the study group and 35.7 +/- 2.5 weeks in the triplets managed expectantly. Newborn hospital days as well as newborn and maternal complications were not statistically different between the management groups. Maternal interventions included tocolytic medication, home uterine activity monitoring, and extended hospitalization, and were more common in the triplets managed expectantly than in the study group of triplets reduced to twins. Multifetal pregnancy reduction for triplet pregnancies does not necessarily improve pregnancy outcome, though it may be offered on the basis of parental choice. PMID- 1876361 TI - Pregnancy outcome following ultrasound diagnosis of macrosomia. AB - Both elective cesarean and early induction have been proposed for pregnancies in which the fetus is suspected to be macrosomic by ultrasound examination. We studied 242 nondiabetic women with estimated fetal weights (EFWs) by ultrasound of at least 4000 g or the 90th percentile for gestational age at 36 or more weeks' gestation. In 66 of 86 women (77%) delivering within 3 days of ultrasound examination, EFW exceeded birth weight. In only 41 of these 86 women (48%) were the EFWs within the corresponding 500-g category of birth weight. A trial of labor resulted in vaginal delivery in 76 of 106 women (72%). There were five cases of shoulder dystocia but no birth trauma. Estimated fetal weights and birth weights were not significantly different between the women who had a trial of labor and those who did not. Our results do not support cesarean delivery or early induction as a means of preventing infant morbidity when fetal macrosomia (weight of 4000 g or more or the 90th percentile for gestational age) is diagnosed by ultrasound. PMID- 1876362 TI - Uterine contraction pressures achieved in parturients with active phase arrest. AB - An adequate trial of labor preceding cesarean delivery for arrest of cervical dilatation in the active phase of labor has not been defined precisely. We reviewed the records of 85 consecutive women at term who received oxytocin for induction or augmentation of labor and who subsequently delivered by cesarean for arrest of labor in the active phase. The mean duration of oxytocin infusion was 15 hours for induction of labor and 8.9 hours for augmentation. Thirty-four (92%) of the 37 women who received oxytocin induction and 44 (92%) of the 48 who had oxytocin for augmentation achieved at least 200 Montevideo units of uterine pressure. All 85 newborns were vigorous at birth and had no complications during their stay in the hospital nursery. Evaluation of uterine contraction pressure can provide a quantifiable end point for the management of oxytocin induction or augmentation of labor. PMID- 1876363 TI - Maternal hemodynamics in pregnancies complicated by hyperthyroidism. AB - The hemodynamics of six pregnant women with hyperthyroidism were studied before and after therapy. Cardiac output was measured by Doppler technique, and blood pressure by automated cuff. When compared with values in euthyroid pregnant women, blood pressure (83.6 mmHg, P less than .001), heart rate (89.2 beats per minute, P less than .001), cardiac output (11.2 L/minute, P less than .001), and stroke volume (123 mL, P less than .001) were significantly elevated. Total peripheral resistance was significantly reduced (609 dyne.second.cm-5, P less than .001). Despite normalization of thyroid indices after therapy, cardiac output remained markedly elevated (9.7 L/minute, P less than .001) and vascular resistance remained reduced (708 dyne.second.cm-5, P = .01). Although the hemodynamics of pregnant thyrotoxic women normalize with therapy, they remain significantly hyperdynamic. PMID- 1876364 TI - Umbilical artery resistance index as a screening test for fetal well-being. I: Prospective revealed evaluation. AB - Abnormalities of the human fetoplacental circulation, a common association with fetal morbidity and mortality, can be detected by Doppler ultrasound examination of the umbilical arterial blood flow. The value of this procedure as a screening test was assessed in 369 women whose fetuses were evaluated on 1354 occasions using both computerized antenatal fetal heart rate (FHR) analysis and continuous wave Doppler ultrasound. The FHR analyses were used to guide management, but the results of the Doppler measurements were not made available to the clinical staff. The mean duration of each nonstress test (NST) was 27 minutes, compared with 6 minutes for the Doppler examination. Increased resistance indices in the umbilical artery identified those fetuses with an abnormal NST or a clinical diagnosis of antenatal distress with a high sensitivity and negative predictive value. The high rate of false-positive results with respect to these two end points was reduced when fetal distress in labor was included as a third end point. The value of the Doppler examination in predicting fetal distress was applicable to appropriately grown as well as small for gestational age fetuses. PMID- 1876365 TI - Umbilical artery resistance index as a screening test for fetal well-being. II: Randomized feasibility study. AB - To determine whether the time taken for fetal assessment could safely be reduced by preliminary screening with Doppler ultrasound, 897 women having fetal assessment in the high-risk unit of the John Radcliffe Hospital, Oxford, were randomly allocated to two groups. In the Doppler group, preliminary assessment was by umbilical artery resistance estimation, and in the fetal heart rate (FHR) group by computerized FHR analysis. To minimize the risk of failing to recognize fetal distress, the criteria for using the nonallocated method as well were deliberately conservative. Thus, 66% of the 1869 Doppler studies done in the Doppler group and 39% of the 2069 FHR tests done in the FHR group needed to be followed by the nonallocated tests. Trained nursing staff performed the Doppler studies as part of their routine duties. Doppler studies were unsuccessful in obtaining a result on 26% of the occasions. Under the above clinical circumstances, preliminary Doppler screening did not reduce the time taken for fetal assessment. There were no significant differences in perinatal outcome between the groups, except that emergency as opposed to elective cesareans were less frequent in the Doppler group. As this finding was not predicted by previous hypothesis, it needs to be confirmed. PMID- 1876366 TI - Doppler evaluation of umbilical and uterine-arcuate arteries in the postdates pregnancy. AB - To assess the correlation between Doppler velocimetry and perinatal outcome in the postdates pregnancy, 75 women who were at least 41 weeks' gestation were evaluated twice weekly until delivery. Evaluation included Doppler velocimetry of the umbilical and uterine-arcuate arteries, as well as nonstress testing and amniotic fluid volume estimation. The mean umbilical artery systolic-diastolic ratio (S/D) was significantly higher in the pregnancies with subsequent abnormal perinatal outcomes than in those with normal outcomes (2.42 versus 2.19; P = .03). Using a receiver operating characteristic curve, an abnormal umbilical artery S/D was defined as 2.40 or greater. Using this value, sensitivity was 57.1% and specificity was 77.8%. Our study suggests that an umbilical artery S/D of 2.40, rather than the more traditionally accepted cutoff of 3.0, may be a useful threshold to identify those postdates pregnancies at high risk for abnormal perinatal outcome. PMID- 1876367 TI - Relationship of small-for-dates sac size to crown-rump length and spontaneous abortion in patients with a known date of ovulation. AB - Spontaneous abortion after established sonographic viability is rare. This study prospectively evaluated 39 late first-trimester abortions after fetal viability was established by ultrasound. The average crown-rump length measurement and mean sac diameter in this group were determined and compared with predicted values based on known conception dates, and the discrepancy between actual and predicted measurements was noted. The same calculations were then made on 39 prospectively matched non-aborting controls. We also determined the difference between sac size and crown-rump length in both groups. Significant differences were found for all three measures. Small-for-dates sac size and small-for-dates crown-rump length were defined as having a discrepancy score greater than 1 standard deviation (SD) above normal. Small-for-dates sac/crown-rump length was defined as having a discrepancy score less than 1 SD below normal. A high percentage of aborters was correctly predicted by a mean sac diameter (82%) or crown-rump length (77%) that was greater than +1 SD, with few false positives (12.8 and 5.1%, respectively). The cutoff for differences of sac minus crown-rump length measurements (10.1 mm) was less sensitive (56%), but just as specific (82%). When both the mean sac diameter and crown-rump length were smaller than expected (according to known date of ovulation), the ability to predict abortion was 71% with few false positives (3.5%). PMID- 1876368 TI - Fetal cardiac abnormalities detected by transvaginal sonography at 12-16 weeks' gestation. AB - The use of transvaginal ultrasound scanning has substantially improved early pregnancy imaging of fetal anatomy. We detected cardiac abnormalities in ten fetuses at 12-16 weeks' gestation using transvaginal ultrasound. PMID- 1876369 TI - Individual growth curve standards in triplets: prediction of third-trimester growth and birth characteristics. AB - We investigated the ability of Rossavik growth models, determined from measurements obtained before 24 weeks (head circumference [HC], abdominal circumference [AC], femur diaphysis length, and estimated fetal weight [EFW]) or 25 weeks (thigh circumference), to predict third-trimester growth and birth characteristics in normally growing triplets. Comparisons of coefficient c values for six anatomical measurements indicated no statistically significant differences in the second-trimester growth of triplets, twins, and singletons. Third-trimester triplet values for HC, AC, and femur diaphysis length were predicted with an accuracy of +/- 6-8%. For thigh circumference and EFW, the comparable values were +/- 17 and +/- 15%, respectively. The HC at birth was predicted without bias; the random error was approximately -27 to 9.0%. Weight, AC, and thigh circumference were systematically overestimated (16.5, 20.9, and 16.3%, respectively). After correction for systematic errors, these characteristics could be predicted with random errors of -13.0 to 9.5% (weight), 12.0 to 2.8% (AC), and -16.7 to 11.3% (thigh circumference). Growth Potential Realization Index values had means of approximately 100% and ranges from 90-121%. The mean triplet value of the Neonatal Growth Assessment Score was 13.6, ranging from 2.8-26.5. These results are similar to those for singletons and twins and indicate that individual assessment of growth in triplets can be performed with the same methods used for both singletons and twins. PMID- 1876370 TI - The impact of National Health Service Corps physicians in the lowering perinatal mortality rate in Dade County, Florida. AB - In some parts of Dade County, Florida, perinatal mortality rates have revealed serious problems in the delivery of health care to poor pregnant women. From 1982 1985, the reported perinatal mortality rates varied from 32-36 per 1000 live births, more than double the national average. Under the leadership of the Primary Health Care Consortium of Dade County (a federation of community health centers and other primary care providers), National Health Service Corps obstetricians and pediatricians served inner-city, medically needy patients as part of a coordinated perinatal plan from 1987-1989. Data on fetal and neonatal deaths, collected from census tracts adjacent to the community health centers, were used to study the impact of Corps obstetrician and pediatrician placement. The respective perinatal mortality rates were compared with those of 1986 as historic controls. Within a year, the overall perinatal mortality rate was reduced by 45%. As a result, an estimated 320 lives were saved between 1987-1989. This public health achievement represents a measurable impact due to assignment of National Health Service Corps physicians and can be used as a working model to reduce perinatal mortality in medically underserved communities in the United States. PMID- 1876371 TI - Pregnancy outcome in an active-duty population. AB - The number of women in the military has grown since the initiation of the all volunteer force. Pregnancy is no longer a justification for discharge from active service. Previously published reports have shown that active military service is associated with poor pregnancy outcomes. We compared a group of active-duty pregnant women (N = 331) matched for age and gravidity with a control group of dependent wives of active-duty personnel (N = 1218). Study variables examined were the incidences of cesarean and operative vaginal delivery, Apgar scores of less than 7 at 5 minutes, preterm complications (preterm labor and premature rupture of membranes) requiring transfer to a tertiary care center, pregnancy induced hypertensive syndromes, intrauterine growth retardation (IUGR) (infant weight less than 2500 g), and pregnancy-related complications. In the active-duty group, the rates of primary cesarean (P less than .001), transfer for preterm complications (P less than .0001), pregnancy-induced hypertensive syndromes (P less than .01), and IUGR (P less than .05) were greater than in the control group. Active-duty servicewomen, despite defined limitations of work and ready access to health care, continue to represent a high-risk population. PMID- 1876372 TI - Utility of Leopold maneuvers in screening for malpresentation. AB - Malpresentation is a common complication of pregnancy. Using ultrasound as the gold standard, we prospectively tested Leopold maneuvers as a screen for nonvertex presentation in the third trimester. In our hands this technique performed poorly. Values for sensitivity, specificity, positive predictive value, and negative predictive value were 28, 94, 24, and 95%, respectively, in a population with a 7% prevalence of noncephalic presentation. Much of the correlation between the screening and diagnostic tests seemed to arise from chance (kappa = 0.13). PMID- 1876373 TI - Evaluation of a rapid enzyme immunoassay test for detection of group B Streptococcus. AB - The purpose of this study was to determine the reliability of the ICON immunoassay in detecting vaginal group B Streptococcus in pregnant women. Vaginal cultures were obtained at the time of sterile speculum examinations from 300 laboring women. The frequency of vaginal group B streptococcal colonization was 10%. A duplicate vaginal swab was used in the immunoassay, which required less than 10 minutes for completion. The immunoassay could reproducibly detect 3+ to 4+ growth (greater than 10(5) colony-forming units per milliliter of vaginal fluid), which was considered heavy colonization. The overall sensitivity, specificity, positive predictive value, and negative predictive value were 33, 95, 43, and 93%, respectively, compared with culture. For heavy colonization (3+ to 4+ growth), the sensitivity, specificity, positive predictive value, and negative predictive value were 100, 95, 32, and 100%, respectively. The immunoassay is a highly sensitive and specific test for detection of heavy vaginal colonization by group B streptococci in obstetric patients, but cultures are required to detect light group B streptococcal colonization. PMID- 1876374 TI - A clinicopathologic study of 153 cases of complete hydatidiform mole (1980-1990): histologic grade lacks prognostic significance. AB - Although the significance of histologic grading in hydatidiform mole has previously been investigated, most studies evaluated patients treated before 1975. Since 1975, many advances have been made in the understanding and treatment of hydatidiform mole, including the division of molar pregnancy into complete and partial hydatidiform mole. We retrospectively studied 153 cases of complete hydatidiform mole diagnosed and treated at the Brigham and Women's Hospital between 1980-1990 to determine the current prognostic significance of histologic grading in this disease. The histologic grade (based on the criteria of Hertig and Sheldon) was compared with the subsequent clinical course, including the rates of spontaneous remission, persistent gestational trophoblastic tumor, metastatic disease, "high-risk" metastatic disease, chemotherapy resistance, and survival. The histologic grade of the original complete hydatidiform mole did not correlate significantly with any index of clinical outcome evaluated. PMID- 1876375 TI - Problems encountered with the Bethesda System: the University of Iowa experience. AB - This paper provides a descriptive summary of 1 year's experience with the Bethesda Cytologic Classification System at the University of Iowa Hospitals and Clinics. Cytotechnologists and pathologists criticized the failure of the new classification system to provide microscopic criteria for the following categories: adequacy of the smear (satisfactory, less than optimal, unsatisfactory), atypical squamous cells of undetermined significance, atypical glandular cells of undetermined significance, and inflammation-associated changes. Clinicians criticized the "less than optimal" category and the reporting of koilocytosis, moderate dysplasia, and endometrial cells. Suggestions for modifying the Bethesda System include: eliminating the less than optimal response, defining what constitutes an unsatisfactory smear, eliminating the terms low-grade and high-grade squamous intraepithelial lesion, and changing the reporting of endometrial cells. PMID- 1876376 TI - Vaginal cuff closure at abdominal hysterectomy: comparing sutures with absorbable staples. AB - To compare two methods of vaginal cuff closure during abdominal hysterectomy, 60 patients were randomized to one of two cuff-closure methods. The vaginal cuff was closed with three interrupted 0-Dexon sutures in 30 and with absorbable staples in 30. Both groups were similar with respect to age, gravidity, parity, preoperative indication, hemoglobin, and hematocrit. The operative technique and quantity of irrigation used was standardized. Operative blood loss was calculated by the weight method and an unactivated, medium flat Jackson-Pratt drain was left in place for collecting postoperative cuff cultures at 24 and 48 hours. The mean operative times in the suture group (97.4 minutes) and staple group (93.4 minutes) were not significantly different (P greater than .05). Cuff-closure time was more rapid (P = .0001) in the staple group (5.8 minutes) than in the suture group (9.3 minutes). Intraoperative cultures were positive in eight of 30 suture patients (26.7%) and eight of 30 staple patients (26.7%). Postoperative cultures at either 24 or 48 hours were positive in four women (13.3%) in the suture group and six (20%) in the staple group. Febrile morbidity occurred in six (20%) in each group. Three staple and two suture subjects developed a vaginal cuff abscess or hematoma, one of whom was readmitted to the hospital for intravenous antibiotics and draining of the vaginal cuff abscess. The presence of a positive vaginal cuff culture did not predict clinical outcome. Based on these observations and the increased cost of the stapling device, we conclude that there is no significant clinical advantage of surgical staples over traditional sutures for vaginal cuff closure at abdominal hysterectomy. PMID- 1876377 TI - A computer method for visual presentation and programmed evaluation of labor. AB - Manual graphing of the progress of labor is considered useful but is not often done. The early detection of some deviations requires special graphics aids. Our objective was to develop an easy-to-use computer program for the integrated visual presentation of information characterizing the progress of labor. Through the use of inexpensive personal computers equipped with graphics monitors, the program provides a combined graphics display of timed progressive cervical dilatation, fetal station, and stimulation of uterine activity (oxytocin infusion). For the early detection of abnormalities, phase-specific normal ranges (reference areas) are displayed. In addition, protraction/arrest as well as precipitate labor disorders are highlighted and computer messages are displayed. The program was evaluated through the assessment of 405 labors entered into a local area network of computers. On average, the program identified 1.5 abnormalities per recorded labor (2.0 for labors resulting in vaginal delivery). The graphic presentation of the labor curve, produced within 3 seconds, displayed 27% more information than the tabular format on the same screen area and provided a single-screen display of the labor curve even for patients with excessive data. The computer-generated display of labor curves facilitates visual presentation and interpretation of labor progress and can also help to translate quality assurance criteria into clinical practice. PMID- 1876378 TI - Preliminary experience with magnetic resonance imaging in patients with third trimester bleeding. AB - Fifteen patients with third-trimester bleeding, in whom transabdominal ultrasound had failed to identify a definitive source of bleeding, underwent magnetic resonance imaging (MRI). Magnetic resonance imaging correctly identified three cases of placenta previa. In four patients, intrauterine blood was identified in hematomas. One hematoma was associated with a previa, two progressed to acute abruptions, and one was associated with a clot at the marginal cord insertion. Blood was seen leading away from the placenta in a case that progressed to an acute abruption. It was also seen in the region of the cervix in two patients with placenta previa. One patient had a normal MRI but had a fresh clot at delivery, which presumably formed after the imaging. In the remaining seven patients, MRI scans were negative and the placentas were normal at delivery. Our preliminary results suggest that MRI is helpful in evaluating patients with unexplained third-trimester bleeding. PMID- 1876379 TI - Finapres: a noninvasive device to monitor blood pressure. AB - Often, obstetric patients are not evaluated in preliminary studies during the development of new medical devices. The purpose of this study was to compare the Finapres digital probe with oscillometric and arterial line devices for recording blood pressures in low- and high-risk pregnant women. A total of 38 women were studied, including 24 with pregnancy-induced hypertension, two with chronic hypertension, two with cardiac disease, and ten who had no risk factors but requested epidural catheter placement. The comparison of Finapres or oscillometric recordings with direct arterial values confirmed that systolic recordings were imprecise for both devices (r = 0.80 and r = 0.64, respectively). Diastolic recordings (Korotkoff sound, phase 4) from the Finapres were accurate compared with the arterial values (r = 0.84). The Finapres performed at least as reliably as the oscillometric monitor in assessing blood pressure in our pregnant population and provided continuous measurements. When very accurate systolic recordings are needed, arterial catheter placement may be necessary. PMID- 1876380 TI - Clinical use of immunoperoxidase markers in excluding ectopic gestation. AB - Ectopic pregnancy is suspected when a pregnancy test is positive and an Arias Stella phenomenon with decidua is seen on endometrial curettings in the absence of chorionic villi and trophoblast. We performed immunoperoxidase stains for beta hCG, hPL, placental alkaline phosphatase, and keratin (AE1/AE3) on endometrial curettings of 72 patients with first-trimester bleeding in whom ectopic pregnancy was suspected based on routine hematoxylin and eosin (H&E) stain. Negative immunoperoxidase stains correlated with a retrospective patient chart review identified only ten patients with extrauterine pregnancy, a prevalence of 14%. The sensitivity of hCG, hPL, placental alkaline phosphatase, and keratin markers in detecting trophoblastic cells in the curettings was 42, 48, 24, and 69%, respectively. Each marker had a specificity of 100%. When both keratin and hPL were used, the sensitivity improved to 73%; however, there was no advantage in using three or more markers. We conclude that 73% of patients suspected to have ectopic pregnancy would be spared additional diagnostic techniques when immunoperoxidase markers for keratin and hPL are used on endometrial curettings without trophoblast on routine H&E stain. The procedure requires only 3 hours of laboratory time. PMID- 1876381 TI - Improving the Cytobrush as an aid in the evaluation of the abnormal Papanicolaou test. AB - In a series of 39 patients undergoing cervical conization, the Cytobrush was used to determine whether dysplasia involved the endocervical canal. To improve the specificity of the Cytobrush for this purpose, a sleeve was designed to guide the brush into the endocervical canal in order to minimize contamination from ectocervical lesions. Both the unsleeved and sleeved Cytobrush demonstrated good sensitivity for detecting dysplasia within the endocervical canal (89 and 95%, respectively). The sleeved Cytobrush demonstrated greater specificity than the unsleeved Cytobrush (90 versus 60%; P less than .05). Compared with endocervical curettage, the Cytobrush used in conjunction with the described "cytosleeve" offers an inexpensive, less painful, and accurate method of determining endocervical involvement of dysplasia. PMID- 1876382 TI - Use of the intestinal isolation bag in gynecologic surgery. AB - Exposure of the operative site during laparotomy is, at times, suboptimal. The major viscera requiring retraction out of the operative field are the small intestines. Usually, multiple cloth laparotomy packs are used to compress and displace the intestines. We describe the use of an intestinal isolation bag to house the small intestines and keep them out of the operative field. Using this technique, laparotomy packs are not required. Because the bag itself takes up very little space, the size of the operating field is not compromised. In addition, the bag does not abrade or desiccate the bowel, potentially reducing serosal injury and adhesion formation. PMID- 1876383 TI - Diagnosis and management of chronic hypertension in pregnancy. AB - Pregnancies complicated by chronic hypertension are at increased risk for the development of superimposed preeclampsia, abruptio placentae, and poor perinatal outcome. The frequency of these complications is particularly increased in patients with severe hypertension and those with preexisting cardiovascular and renal disease. Such women should receive appropriate antihypertensive therapy and frequent evaluations of maternal and fetal well-being. In contrast, in patients with mild essential chronic hypertension, the maternal and perinatal benefits from antihypertensive medications are highly controversial. A review of the literature revealed two placebo-controlled studies, four trials comparing treatment versus no medication, and three comparisons of methyldopa and oxprenolol. In only one of these studies were subjects randomized in the first trimester. No differences in pregnancy outcome were found with the use of antihypertensive drugs. Evaluation of the woman with chronic hypertension who is considering pregnancy should begin before conception to establish the cause and severity of the hypertension. Appropriate management should include frequent evaluation of maternal and fetal well-being; antihypertensive medications may be useful in patients with severe disease as well as in those with target organ involvement. PMID- 1876384 TI - Counseling the infertile couple: when enough is enough. AB - Therapy of infertility rarely offers a clear end point for cessation after repeated failure. Yet fertility treatment, especially if repeatedly unsuccessful, is associated with economic as well as emotional cost. Stopping treatment becomes an increasingly important option for couples whose therapy does not produce the desired result. It is the clinician's obligation to make infertile couples aware of this option early in the treatment plan and to give specific suggestions that allow these couples to stop treatment at a medically arbitrary, yet temporally well-defined point. To this end, we suggest the following for infertile couples undergoing treatment: 1) an ongoing relationship with a qualified counselor; 2) the best estimates for pregnancy rates, including the background (treatment independent) rate, for all forms of treatment available at any point in time; 3) the option of stopping treatment from the start; 4) encouragement to seek second opinions throughout treatment; 5) time off from treatment; and 6) the opportunity to set arbitrary but relatively firm time limits. Incorporation of these suggestions into the therapeutic plan for infertile couples underscores the imperfect nature of infertility treatment and acknowledges that sometimes the most we can do for our patients is to help them stop. PMID- 1876385 TI - Abortion: is there a rational precept? AB - Recent Supreme Court rulings have augmented the potential role of the individual states in abortion regulation. As a result, largely political influences have escalated the abortion debate to the point that there is currently no identifiable center, and consensus seems impossible. The traditional concept of viability has proven an inadequate basis for extension of personal rights and protections to the fetus. Conservative interpretation of a proposed neurologic definition of human life would suggest that human life does not start until approximately 70 days post-conception. Standardization and widespread acceptance of a definition of "brain life" would potentially clarify many medical and legal questions regarding elective abortion and would parallel currently accepted medical and legal definitions of death. PMID- 1876386 TI - The effect of the New York State restrictions on resident work hours. AB - New York state has recently restricted the hours that residents may work to an average of 80 hours per week. We have complied with these regulations through the addition of nonresident personnel, including attending physicians, a physician assistant, and nurse midwives. This study was designed to assess the effect of these changes on our residents. A questionnaire covering the effects of our new system was distributed to both attending and resident staff. Surgical case load and Council on Resident Education in Obstetrics and Gynecology (CREOG) scores since the change were compared with those of previous years. A marked improvement in resident life-style was noted. Although residents commented that they had increased time for reading, this was not reflected in an improvement in the CREOG scores. The quality of patient care was not felt to be improved, and the continuity of care was considered to be adversely affected. Resident surgical case load was unchanged. The assignment of emergency room coverage to attending physicians and gynecologic floor coverage to a physician assistant was seen as having a detrimental effect on resident experience. We conclude that the new restrictions on resident work hours in New York have improved resident quality of life. However, there does not appear to be an improvement in patient care, which was the original intent of the statute. Concerns are discussed about the effect of this decrease in hours worked on resident experience and education. Further research is needed to assess the long-term effects of reduced resident work hours on both patient care and resident education. PMID- 1876387 TI - Elevated serum testosterone, hirsutism, and virilism associated with combined androgen-estrogen hormone replacement therapy. PMID- 1876388 TI - Dynamic urethral pressure profilometry pressure transmission ratio: what do the numbers really mean? PMID- 1876389 TI - Ultrasonic surgical aspiration in the treatment of vulvar disease. PMID- 1876390 TI - Methotrexate treatment of ectopic pregnancy. PMID- 1876391 TI - Do morbid outcomes increase with restraint use? PMID- 1876392 TI - The AIDS patient and the last ICU bed: scarcity, medical futility, and ethics. PMID- 1876393 TI - Quality assessment with a computerized anesthesia information management system (AIMS). AB - Private practice anesthetists are skeptical about the worth of quality assessment programs because of the difficulty of creating and maintaining an accurate and efficient medical record, the paucity of data caused by the recent shift in emphasis from process to outcome data, the tendency of adverse outcomes to be presented with no denominators, the lack of integration between process and outcome data, and the tendency for quality assessment programs to require duplicate documentation. An efficient anesthesia information management system (AIMS) gathers accurate, complete, and legible information before, during, and after each anesthetic procedure. One such system used in a private practice setting at Burbank Hospital, Fitchburg, Massachusetts, has a computerized data base to draw from preoperative, intraoperative, and postoperative events, with a judicious selection of both process and outcome indicators. The clinical anesthesia data base can be an effective tool for practical and efficient clinical competency evaluations and can lead to many improvements in the quality of anesthesia care delivery. PMID- 1876394 TI - Downstream outcomes: using insurance claims data to screen for errors in clinical laboratory testing. AB - A methodology is described by which health insurance claims data might be used to discover the occurrence of systematic errors by clinical laboratories. False positive results should generate a series of tests or treatments that are eventually abandoned as the false signal of the initial test is discovered while false-negative results may cause necessary tests or treatments to be unduly delayed. False results may also generate adverse outcomes such as an unusually high number of deaths or hospitalizations among persons who have received particular laboratory tests. Health insurance claims data may be used to discover these patterns and how the inclusion of laboratory results on claims would improve the precision of such inferences. Appropriate statistical tests are discussed. PMID- 1876396 TI - [Total knee endoprosthesis]. PMID- 1876395 TI - Teaching the tenets of quality: a survey of medical schools and programs in health administration. AB - This article reports the results of a survey of medical schools and programs in health administration to determine the national scope of the teaching of quality assurance in higher education. The responses from 98 medical schools and 64 schools of public health or health administration programs suggest that medical schools have not yet successfully integrated training in QA into the medical school or residency curriculum. Health administration programs appear to give QA courses more serious attention, to offer a more well-rounded program in QA, and to evaluate students' progress in QA courses more carefully. No statistically significant differences were found between public and private medical schools, between undergraduate and graduate levels, or across geographic regions in response rates or in provision of QA training. PMID- 1876397 TI - [Endoprosthesis of the knee joint: current status and trends]. AB - Knee joint endoprosthetics has proved to be at least as successful as hip joint endoprosthetics, although the total implantation rate has risen to only about 15%, which ignores its widespread unpopularity. There is a great variety of artificial knee joints, although according to ISO standards all models can be reduced to four basic ones. Deciding to use a stabilized, semi-constrained or unconstrained artificial knee prosthesis requires careful consideration especially if the possibility of its removal is taken into account. The main reason for unsatisfactory clinical results is still retropatellar pain. Intensive basic research is necessary in this area as well as in the development of new materials that might be used for new prosthetic designs. Designers as well as surgeons should aim at regaining the natural function level with no pain for the patient. PMID- 1876398 TI - [Sled prosthesis, rotating knee and hinge prosthesis: St. Georg model and ENDO model. Differential therapy in primary knee joint arthroplasty]. AB - During the last 20 years the surgeons at the ENDO Klinik in Hamburg have implanted more than 7,000 cemented primary knee prostheses of their own design, formerly the St. Georg models and now the ENDO models. The sled prosthesis, rotating knee and hinge prosthesis are each stabilized to a different degree. The indication depends on the type of deformity, the disease. affecting the knee and the type of patient. As a result of our experience with the three systems they are now implanted in the ratio of 30:60:10, and we are convinced that in order to treat all problems encountered in diseased knees it is essential to have different prostheses with various degrees of stabilization. PMID- 1876399 TI - [Intermediate results of kinematic knee prosthesis]. AB - A retrospective study of 88 of 117 kinematic total knee prostheses was carried out at the Department of Orthopaedics, University Clinic, Innsbruck. In 71 cases the clinical and functional score of the knee Society was applied. Radiographs were taken under fluoroscopic control. In 3 cases, the need for revision surgery was already obvious. A slight varus angle of 2.1 degrees became apparent. Flexion contracture showed a correlation with the inclination of the femoral component. Radiolucencies of the tibial component showed up in cases with a reduced tibial angle. Radiolucencies of the patella component correlated with lateral subluxation. PMID- 1876400 TI - [2- to 5-year follow-up of cementless implantable knee joint prosthesis of the Miller-Galante type]. AB - Based on a prospective study protocol, the two- to five-year results of the Miller-Galante cementless total knee arthroplasty are presented. Sixty-four implants were placed in 59 patients: 60 implantations were cementless and 4 cemented. Clinically, the scores for pain, range of motion, walking and stair climbing improved significantly. Radiographically, the uncemented components displayed no signs of definite or possible loosening, whereas one of the cemented components was found to be definitely loose. On histological evaluation of the retrieved implants, all components had bone ingrowth. PMID- 1876401 TI - [The GSB knee joint: reoperation and infections]. AB - The GSB-III knee prosthesis is one of the semi-constrained types and consequently ranks between the non-constrained condylar prostheses and the fully constrained hinges. Its kinematics can be classified as "physiological" in the sagittal plane as far as the relationship between femur and tibia in the various degrees of flexion is concerned, which is a replica of a normal knee joint. The high average range of postoperative mobility as well as the extremely low aseptic loosening rate after 10 years prove the truth of this statement. A simple operative technique requiring a few special instruments allows even the less experienced knee surgeon to be successful and to obtain good results in cases with severe deformity and poor bone quality. The survival curves of the GSB-III prosthesis (n = 638) show a cummulative success rate of over 90% after 10 years. Looking separately at cases complaining of more or less severe pain, we frequently find underlying patellar problems, the main cause for revisional surgery. This problem is not specific for our prosthesis, but must be considered a so far unsolved worldwide problem. Infections are another relatively frequent cause for revisions. Disturbed wound healing, arterial insufficiency and malignant rheumatoid arthritis are the outstanding risk factors. For a reliable comparison of the different knee prostheses we ought to have a globally accepted evaluation system, which unfortunately still does not exist. PMID- 1876402 TI - [Hinge endoprosthesis of the knee joint. Long-term results based on the Blauth prosthesis]. AB - Knee prostheses of the condylar or hinge type have constructional features that have both advantages and disadvantages. Both types are compromises as a result of different demands. Here we report long-term results with the Blauth prosthesis as an example of the efficiency of the hinge concept. The Blauth prosthesis is constructed according to the low-friction principle without a weight-bearing axis. Load transmission to the bone is accomplished by large interface areas. The sliding bearing of the patella is oriented perpendicular to the transverse axis of rotation. A prospective multicentric study reports on 511 prosthesis with a follow-up between 1 and 15 years. Aseptic loosenings were confirmed in 1.2% of the patients, deep infections in 3.3%. The survival analysis showed a probability of 89% that a prosthesis would not have a deep infection or loosen. A hinged knee prosthesis shows positive long-term results even compared with the condylar types if the relevant principles of construction are adequately considered. PMID- 1876403 TI - [Continuous passive motion in the after care of knee joint prostheses]. AB - Since 1982 there have been many reports on the use of continuous passive motion in the postoperative care of patients with total knee arthroplasty. Continuous passive motion (CPM) has proven to provide good results at our clinic. CPM is often described as having a positive effect on the postoperative range of motion. It also seems to decrease the length of the hospital stay. In addition, a low incidence of thrombosis has been reported and we could detect no negative effects on wound healing. PMID- 1876404 TI - [Failures of knee joint prostheses. An analysis of knee prostheses and component revisions, 1980-1987]. AB - Total knee arthroplasty has become more common in the last 20 years as a result of the continuous improvement in prosthetic design and operative techniques. Therefore, there have also been more failures. To show the reasons for these failures and the difficulties and results of revision surgery we studied the 48 uni- or tricompartmental revisions of total knee arthroplasties we performed in our institute between 1980 and 1987. Twelve to 94 months (mean 40.4) after revision we found 66% good or very good results. The main reason for failure was a poor surgical technique, which we found in 69% in unicompartmental, and in 28% in tricompartmental prostheses. Revision surgery needs a high level of practical knowledge and flexibility. The main problems consist of correction of the alignment and the filling of bone defects. Thus, we reconstructed ten large defects at the tibial plateau, which resulted in one very good, seven good and two moderate results. PMID- 1876405 TI - [Problems of infected knee prosthesis]. AB - Our report is based on 47 infected knee arthroplasties that were revised and followed up in our hospital between 1984 and 1990. Various surgical and therapeutic management options are assessed. In our patient population our experience revealed that the two-stage reimplantation seemed to offer the best chances for management of infected knee arthroplasty. Infections with gram negative bacteria tend to take a less favorable course than those caused be gram positive organisms. A division into categories of infected knee joints is presented and the complexity of problems related to the diagnosis is discussed. PMID- 1876406 TI - [Mid- to long-term results after treatment of 118 cases of periprosthetic infections after knee joint replacement using one-stage exchange surgery]. AB - From 1976 to 1985, 157 periprosthetic infections after knee arthroplasty were treated surgically at the ENDO-Klinik in Hamburg. Of these, 118 cases underwent one-stage revision arthroplasty using specific antibiotic-loaded cement; 104 were available for analysis after a postoperative follow-up period of 5-15 years. Seventy-six cases were cured as a result of this single operation. This number was increased to 84 by a repeated operation in cases that had failed to respond to therapy. In 20 cases one-stage revision arthroplasty failed in the treatment of periprosthetic infections after replacement of the knee joint. PMID- 1876407 TI - Pennsylvania Medical Society membership directory 1991-1992. PMID- 1876408 TI - Patient care threatened by presence of concentrated lidocaine syringes. PMID- 1876409 TI - PNA member Lee Levin: an entrepreneurial profile. Interview by Kimberley Jackson. PMID- 1876410 TI - Rural nurses need more AIDS education. PMID- 1876411 TI - Commission of Women spearheads study of gender bias in court system. PMID- 1876412 TI - Gender gap in research hit by ANA. PMID- 1876414 TI - Career paths. PMID- 1876413 TI - Supreme Court ruling on family planning violates free speech, professional ethics. PMID- 1876415 TI - AIDS protection is patient's right. PMID- 1876416 TI - ANA launches childhood immunization campaign. PMID- 1876417 TI - Validation of hourly pain intensity profiles with chronic pain patients. AB - This study examines how empirically derived pain intensity profiles relate to psychological adjustment in chronic pain patients. Hourly pain intensity ratings over the course of a day of 189 chronic pain patients were categorized into 6 groups using a hierarchical regression analysis technique. The profiles reflected linear, curvilinear, multilinear or "no profile" effects. Judges' ratings of pain intensity profiles were found to be less reliable than ratings based on empirical analysis. The majority of patients showed linear profiles while 26% of the patients showed no consistent relationship between hourly pain intensity and time of day. Patients who showed no consistent trend in their pain ratings reported having significantly higher ratings of emotional distress. They tended to have conflicts at home and showed more pain behavior than patients who had a distinct pain profile. Support is given for the potential clinical utility of pain rating profiles. PMID- 1876418 TI - Relationship between perceived self-control of pain, pain description and functioning. AB - Recent research has shown an association between preferred coping style and pain report. The present study explores in a sample of 51 patients with chronic pain of myofascial origin the relationship between a dispositional measure of coping, the internality dimension of the Pain Locus of Control Scale (PLOC), and ratings of pain intensity, frequency, and pain-related behavioral functioning. Patients above the median on the internality dimension of the PLOC reported their pain as less intense and frequent than those below the median. No differences were noted on the behavioral functioning measures. Results are consistent with previous studies and indicate an association between ability to control pain and variations in magnitude and periodicity of pain. The clinical implication of the data is that strategies which provide reduction in pain intensity and frequency might be expected to result in increased perception of personal control of pain. PMID- 1876419 TI - Mechanism of analgesia induced by hypnosis and acupuncture: is there a difference? AB - Hypnosis and acupuncture can alleviate experimentally induced pain but the mechanism of analgesia remains unclear for both techniques. Experimental pain was induced by cold pressor test (CPT) in 8 male volunteers. Analgesic effect of hypnosis (HA) and acupuncture (AA) was assessed before and after double-blind administration of placebo or naloxone, in a prospective, cross-over study. We found that pain intensity was significantly lower with HA as compared with AA, both with naloxone (P less than 0.001) and placebo (P less than 0.001). Within HA or AA groups, pain scores did not differ significantly when naloxone or placebo was administered. During AA, however, pain scores were similar to control values when naloxone was given (P = 0.05) but decreased significantly with placebo (P less than 0.002). Analog scales for pain intensity and pain relief showed a good correlation (r = 0.94). Plasma levels of beta-endorphins did not change significantly in any combination. Heart rate, peripheral arterial blood pressure and skin conductance were very insensitive indices to assess pain intensity or relief, as well as intensity of acupuncture stimulation or depth of hypnotic trance. We conclude: (1) HA and AA can significantly reduce pain from CPT, and HA is more effective than AA: (2) HA and AA are not primarily mediated by the opiate endorphin system; and (3) plasmatic levels of beta-endorphins are not significantly affected by either HA or AA nor by naloxone or placebo administration. PMID- 1876420 TI - Local toxicity with subcutaneous methadone. Experience of two centers. AB - We report on 8 patients treated with subcutaneous methadone for cancer-related pain at 2 institutions. The success of other subcutaneous agents for pain control has been well demonstrated. It was felt that methadone would be useful due to its low cost. Unfortunately, 7 of the 8 patients experienced adverse reactions at the subcutaneous sites requiring cessation of subcutaneous methadone. PMID- 1876421 TI - Subcutaneous lidocaine for treatment of neuropathic cancer pain. AB - Three patients with terminal malignancy reporting ineffective analgesia using systemic and subsequently spinal opiates were treated with subcutaneous infusion of 10% lidocaine hydrochloride. During the infusion, reasonably stable blood concentrations were achieved and maintained using a subcutaneous infusion at varying dose rates over days to months with improvement of the pain complaints which continued to be refractory to conventional analgesics. Blood lidocaine levels obtained at regular intervals revealed effective concentrations between 2 and 5 micrograms/ml for each patient. PMID- 1876422 TI - An open label study of oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough cancer pain. AB - Ten patients with advanced cancer and breakthrough pain between the ages of 39 and 78 received oral transmucosal fentanyl citrate (10-15 micrograms/kg) 4 or 5 times each over 2 days (42 total administrations) in an open study. Baseline vital sign and rating scale results did not vary over administrations, except for heart rate which showed an 8 beats/min decrease over 4 administrations. Heart rate and oxygen saturation did not vary significantly over 120 min of evaluation, and minimal changes in blood pressure and respiration rate were found. Significant reduction in pain scores as measured by a pain descriptive scale, the McGill-Melzack scale, and a numeric (VAS) scale were seen at all evaluations from 5 to 120 min. Average time to onset of pain relief was 9.5 min after administration. Wellbeing was significantly increased at all evaluations. Activity level as recorded by the investigator was significantly reduced from 10 to 30 min after administration, however, activity level as reported by the patient was significantly increased at 5 min and from 60 to 120 min after OTFC administration. There were no significant adverse effects. PMID- 1876423 TI - Long-term results of peridural morphine in 225 patients. AB - The long-term results of peridural morphine in 225 cancer patients have been evaluated. Two methods were employed: percutaneously implanted catheter (175 patients) and subcutaneous reservoirs (50 patients). In the 225 patients, the mean duration of implantation of the peridural catheter was 47.3 days (7-420 days), the mean daily dose of morphine was 13.4 +/- 6.9 (5-80 mg) delivered by 2.6 +/- 0.7 (1-8) injections. The mean duration of action was calculated to be 9.3 +/- 3.8 h (3-32 h). Satisfactory analgesia was achieved in 133 patients (59.1%) in whom peridural morphine was the sole analgesic treatment. Peridural morphine appeared to be especially effective in patients with pain arising in the abdominal region. Complications due to morphine and the catheter were evaluated. PMID- 1876424 TI - Ischaemic spinal cord lesion following percutaneous radiofrequency spinal rhizotomy. AB - Two patients are presented in whom percutaneous radiofrequency spinal rhizotomy was complicated by contralateral paresis. Both patients were elderly and suffered from cardiac failure, chronic obstructive respiratory disease, and generalized vascular disease. Investigation of the paresis indicated a contralateral ischaemic cord lesion. It is suggested that local haemodynamic changes induced by heat-mediated rhizotomy may compromise oxygen delivery to the adjacent cord, especially in the presence of pre-existent cardiovascular disease. PMID- 1876425 TI - Tardive dyskinesia and chronic pain. AB - Psychotropic drugs are frequently used to treat chronic pain. Tardive dyskinesia is a serious complication of such therapy, but is not mentioned in the pain literature. Two cases are reported and the implications discussed. PMID- 1876426 TI - The effect of 'detailing' on physicians' prescribing behavior for postsurgical narcotic analgesia. AB - Physicians have been frequently reported to prescribe inadequately pain medication in the hospitalized patient. A number of methods and techniques have been attempted to alter this phenomenon including audit, standard setting, drug utilization evaluation and sanctioning. The purpose of the following study was to demonstrate the behavioral efficacy of the technique of detailing. We reviewed the postsurgical records of 320 patients for pre-established criteria on the administration of meperidine before and after detailing of the proper prescribing with regard to timing and dose. The data show 30% of the sample meeting the criteria before detailing and 43% after detailing had been given. We conclude the method of detailing can be effective in altering physician's prescribing behavior for meperidine in postoperative surgical patients. PMID- 1876427 TI - Functional properties of spinomesencephalic tract (SMT) cells in the upper cervical spinal cord of the cat. AB - Response and receptive field properties were evaluated for 62 spinomesencephalic tract cells in the upper cervical spinal cord (C1-C3) of cats anesthetized with sodium pentobarbital and alpha-chloralose. Recordings were made from cells in laminae I-VIII and X contralateral to antidromic stimulating electrodes positioned in the rostral, caudal and intercollicular region of the midbrain. The mean antidromic threshold for all cells was 185 +/- 132 microA, and conduction velocities ranged from 2.3 to 38.6 m/sec. Twelve cells were backfired from both midbrain and diencephalic stimulation sites. Receptive fields ranged from simple, i.e., ipsilateral forelimb or face, to complex, i.e., excitatory and/or inhibitory responses from large portions of the body. Peripheral receptive fields included muscles, joints, cornea, dura, forelimbs, hind limbs, tail, and/or testicles. Five functional classes of cells were observed: (a) wide dynamic range (14 cells); (b) high threshold (2 cells): (c) low threshold (4 cells); (d) deep/tap (11 cells); and (e) non-responsive (31 cells). Eight cells were evaluated for responses to different doses (5-150 micrograms) of intravenous (i.v.) serotonin. Two of the 8 cells exhibited excitatory effects, whereas 2 cells classified as deep/tap and 4 cells classified as non-responsive were not affected. The results of this study have shown the upper cervical component of the spinomesencephalic tract is made up of a heterogenous population of cells involved in the integration of varied inputs from large portions of the body. It is proposed that the large population of SMT cells in the upper cervical spinal cord may be involved in pain mechanisms, especially those related to the affective consequences of acute and chronic pain. PMID- 1876428 TI - Short-latency excitatory postsynaptic potentials are evoked in primate spinothalamic tract neurons by corticospinal tract volleys. AB - The responses of 8 wide-dynamic-range (WDR) STT neurons to electrical stimulation of the sensorimotor cortex or the cerebral peduncle were recorded intracellularly in anesthetized monkeys. EPSPs and spikes were evoked in STT neurons with short latencies ranging from 0.4 to 5.3 msec after the corticospinal volley, indicating a monosynaptic connection in at least some STT neurons. Spatial and temporal summation seem necessary for the cortex to maintain an effective excitatory influence on STT neurons. It is postulated that the cortical facilitation of STT neurons helps them to acquire more nociceptive signals during behavioral tasks such as exploring a new object so that the brain can make decisions about whether to continue or to abandon a certain task. Possible implications for central pain states are discussed. PMID- 1876429 TI - The formalin test in mice: the influence of ambient temperature. AB - The ambient temperature had a confounding influence on the licking response in the formalin test. No effect was demonstrated in the early phase. In the late phase, the licking activity was much lower at 20 degrees C than at 25 degrees C. Both the intensity and the duration of the response were increased by increasing the ambient temperature from 20 degrees C to 28 degrees C. 5,6 Dihydroxytryptamine lesions of descending serotonergic pathways induced an increase in the nociceptive response at an ambient temperature of 20 degrees C, while the response was no different from control values at 25 degrees C. Differences in paw skin temperature may explain these temperature dependent effects. It was concluded that control of the ambient temperature is necessary to obtain reliable results in the formalin test, late phase. PMID- 1876431 TI - The use of experimental pain in evaluating the effects of dorsal column stimulation on clinical pain. PMID- 1876430 TI - Comments on 'Parturition pain treated by intracutaneous injections of sterile water,' by L. Ader, B. Handsson and G. Wallin (Pain, 41 (1990) 133-138) PMID- 1876432 TI - Toward an integrated understanding of fibromyalgia syndrome. I. Medical and pathophysiological aspects. AB - Fibromyalgia syndrome (FS) is a chronic pain disorder characterized by diffuse musculoskeletal soreness, stiffness, non-restorative sleep and psychological disturbance. At present, much about the etiology, pathological mechanisms and course of FS are unknown. Indeed, standardized diagnostic criteria have only been recently agreed upon. The present paper is the first of a two-part series which reviews the extant empirical literature concerning FS, with a view to arriving at an integrated understanding of the syndrome. The present paper describes the clinical presentation of FS and historical conceptualizations of the disorder. Available research on pathophysiological mechanisms in FS is then presented. In this section we have included literature concerning histology of muscle, sleep architecture, neurotransmitter anomalies and neuropeptide involvement in FS symptomatology. PMID- 1876433 TI - Toward an integrated understanding of fibromyalgia syndrome. II. Psychological and phenomenological aspects. AB - The present paper is the second of a 2-part series in which extant empirical literature concerning fibromyalgia syndrome (FS) is reviewed in order to provide a preliminary approach to forming an integrated understanding of the syndrome. Research on psychological disturbance in FS is reviewed with particular emphasis on affective dysfunction among FS patients. The phenomenology of FS is then described. We attempt to suggest that FS represents a quantitatively and qualitatively experience distinct from similar chronic pain syndromes. Substantive findings in FS research are summarized in the final section and potential ways in which these findings might be integrated to provide a more cohesive model for future research are suggested. PMID- 1876434 TI - The effects of dorsal column stimulation on measures of clinical and experimental pain in man. AB - Despite the extensive use of dorsal column stimulation (DCS) for the control of various chronic pain conditions, most clinicians report only modest success rates. Surprisingly, there has been little placebo-controlled investigation of its efficacy for altering either clinical or experimental pain perception. The current study compared the effects of DCS to placebo stimulation on clinical pain perception, perceived intensity of painful heat stimuli and visual stimuli, and the discrimination of small changes in noxious heat intensity and in light intensity. We found that DCS, but not placebo stimulation, significantly altered ratings of spontaneous clinical pain as well as those of painful cutaneous heat. In addition, heat discrimination thresholds were increased by DCS, but not placebo. On the other hand, DCS had no effect on ratings of visual stimulus intensity nor on visual discrimination, suggesting that the DCS modulation of pain perception was not due to a general change in attention. These data indicate that DCS significantly alters pain transmission in humans. Nevertheless, the relatively small reduction in clinical pain (less than 30%) must be weighed against the invasive nature of electrode implantation. PMID- 1876435 TI - Comparison of human pain sensation and flexion withdrawal evoked by noxious radiant heat. AB - The purpose of this study was to determine the reliability of flexion withdrawal magnitude as an indicator of pain sensation. In 10 healthy human volunteers, we compared the magnitude and latency of integrated biceps EMG with the subjects' rating of pain, using a visual analog scale, elicited by noxious radiant heat stimuli applied to the dorsal forearm. The magnitude and inverse latency of withdrawal, although variable, increased exponentially as a functions of stimulus temperature. The stimulus response functions for mean withdrawal magnitude and mean pain intensity were similar for lower stimulus temperatures, but at higher temperatures the withdrawal continued to increase exponentially whereas pain intensity reached a plateau. The pain intensity and withdrawal magnitude for each stimulus were poorly correlated. Under the conditions of this experiment, mean pain intensity and mean withdrawal magnitude were both well correlated with stimulus temperature, but the magnitude of withdrawal did not reliably reflect the intensity of pain sensation. PMID- 1876436 TI - Spinal and supraspinal correlates of nociception in man. AB - The objective of this work was to simultaneously measure pain-related spinal and supraspinal physiological responses in humans. The sural nerve compound action potential (CAP), the spinal withdrawal reflex (RIII), the somatosensory evoked potential (SEP) and subjective magnitude ratings were elicited by electrical stimulation of the sural nerve in 10 healthy subjects. The sural nerve CAP was used to normalize the evoking stimulus current and to help identify the peripheral nerve afferent types contributing to the physiological and psychophysical responses. Normalizing stimulus current to a proportion of that which elicited a just maximal sural nerve CAP significantly reduced individual variability in magnitude ratings, the RIII and the SEP. Pain and RIII responses only occurred at stimulus levels that were greater than or equal to 1.5 x that which produced a just maximal sural nerve CAP and both responses were positively related to stimulus intensity above that level. Activity in the large diameter A beta fibers will be saturated at stimulus levels near that which produced a just maximal CAP, which implies that both the pain and RIII responses can be attributed to recruitment of the smaller diameter A delta fibers. Although the amplitudes of the P200 and P300 peaks of the SEP were significantly related to stimulation at noxious levels, both were also affected by stimulation at innocuous levels. This result implies that these peaks receive contributions from both noxious and innocuous somatosensory processes. Clearly, the non-pain-related components of these SEP peaks must be identified and isolated before their potential in measuring supraspinal nociceptive processes can be fully realized. PMID- 1876437 TI - Efficacy of ICS 205-930, a novel 5-hydroxytryptamine3 (5-HT3) receptor antagonist, in the prevention of migraine attacks. A complex answer to a simple question. ICS 205-930 Migraine Study Group. AB - To investigate whether the novel, potent and highly selective 5 hydroxytryptamine3 (5-HT3) receptor antagonist ICS 205-930 can prevent migraine attacks, we conducted simultaneously two randomized, double-blind, placebo controlled, multicentre, international trials, involving a total of 204 patients, suffering from classic or common migraine. Both trials had the same parallel group design (1 month baseline observation, followed by 3 months treatment) and both produced remarkably similar results. The primary efficacy parameter was the proportional reduction in attack frequency recorded after 3 months of treatment. Twenty-two patients withdrew prematurely from the trials and could not be assessed for efficacy. Mild to severe constipation was reported by about 50% of the patients on active treatment. None of the doses of ICS 205-930 tested (50 mg, 25 mg and 15 mg daily) produced a statistically significantly better result to reduce attack frequency than did placebo. However, confidence intervals for the difference in effect with placebo were wide, indicating that 15 mg ICS 205-930 may produce a 57% reduction in attack frequency as compared to placebo. The most unusual finding was that, for all efficacy parameters, the best results were obtained with the lowest dose (15 mg), the worst results with the highest dose (50 mg) and an intermediate effect with 25 mg. Such an inverse relation between dose and efficacy suggests a bell-shaped dose-response curve, implying that doses lower than 15 mg might well prove to be more effective. Thus, the present study has produced inconclusive, but intriguing results. Lower doses should be further investigated before drawing any definite conclusion on the efficacy of ICS 205 930 in the prophylactic treatment of migraine. PMID- 1876438 TI - Prediction of postoperative pain and duration of hospitalization using two anxiety measures. AB - This study examined the extent to which measures of anxiety could predict pain and the length of hospitalization following surgery in 111 patients with gallstones over and above what could be predicted on the basis of biographical and medical status variables. Self-reported pain on the third day postoperative could hardly be explained by the variables measured. Preoperative anxiety did not increase the value of the prediction. Age, type of surgery, cystitis and wound infection explained a significant proportion of the variance in postoperative hospital stay. Over and above these variables. A-state on the third postoperative day and also A-state and specific anxiety measured 1 day before surgery exerted a significant increase on the values of prediction of the length of postoperative hospitalization. PMID- 1876439 TI - Preparing children for venous blood sampling. AB - A convenience sample of 100 children, aged 6-12 years, attending Kuwait government hospital laboratories for venous blood sampling was studied. A picture book was used to prepare half of the children for the procedure. Preparation was carried out just prior to sampling and took less than 5 min. The story provided a simple description of venous blood sampling, and why it is carried out; it stressed that the pain is noticeable but not unbearable, and that children will experience less pain if they relax their arm and cooperate with the technician. Prepared children reported significantly less pain, and radial pulse rates confirmed that they were less distressed by the procedure. Observers' and parents' evaluations also indicated that prepared children coped better. Various explanations for the benefits observed are discussed, together with requirements for managing the pain, fear and stress experienced by children during medical treatment. PMID- 1876440 TI - Central pruritus. Case report. AB - An 82-year-old woman experienced generalized pruritus not due to skin or systemic disease. Scratching the skin with a needle induced a crisis of intense pruritus, insensitive to any drug. The pruritus had the characteristics of a central sensation. PMID- 1876441 TI - Effects of sympathectomy in a model of causalgiform pain produced by partial sciatic nerve injury in rats. AB - In a previous report we presented a novel behavioral model of neuropathic pain disorders, produced in rat by a unilateral ligation of about half of the sciatic nerve. The model is characterized by rapid onset of behaviors suggesting spontaneous pain and disordered responses to non-noxious and noxious stimuli. These include reduced withdrawal thresholds to repetitive touch in the partially deafferented skin ('touched-evoked hyperesthesia'), touch-evoked allodynia, reduced withdrawal thresholds to noxious thermal stimuli and exaggerated responses to noxious heat and mechanical stimuli ('thermal hyperalgesia'). Some of these disorders are seen at mirror image sites on the hind limb opposite the lesion. These disorder start within hours after partial nerve injury, last many months and are very similar to causalgia in humans following partial nerve injury. Since sympathetic efferent activity is known to aggravate causalgia in humans and sympathectomy is known to relieve it, we studied the effect of changing sympathetic outflow in the rat model. Reversible sympathectomy was carried out using guanethidine injected intraperitoneally in 3 experiments, each at a different time in relation to the partial nerve injury. We found that: (1) sympathectomy performed several months postoperatively alleviated the sensory disorders bilaterally; (2) sympathectomy prior to nerve injury partially prevented the appearance of thermal hyperalgesia but did not affect hyperesthesia to repetitive touch; and (3) sympathectomy at the time of nerve injury aggravated the sensory disorders during the first few days. As maintenance and production of the sensory disorders in this animal model depended on sympathetic nervous outflow, we conclude that the rats were suffering from a syndrome analogous to sympathetically maintained causalgia in man. PMID- 1876442 TI - Tissue donors: painful nerve lesions and reflex sympathetic dystrophy. PMID- 1876443 TI - Considerations on taxonomy of pain. PMID- 1876444 TI - Decreased clinic utilization by chronic pain patients after behavioral medicine intervention. PMID- 1876445 TI - Pulmonary function in the patients submitted to lung exeresis. AB - The effects of lung surgery on respiratory function were investigated in 80 patients; 17 patients were submitted to left pneumonectomy (LPN); 11 patients were submitted to right pneumonectomy (RPN); 7 patients underwent a left upper lobectomy (LUL); 16 patients a left lower lobectomy (LLL); 17 patients were submitted to right upper lobectomy (RUL); 12 patients underwent right lower lobectomy (RLL). All patients were submitted to spirometry and arterial blood gas analysis. The effects of lung surgery on respiratory function depends upon the extent of the resected tissue. PMID- 1876446 TI - Cardiological risk in patients undergoing abdominal aortic aneurysm surgery. An analysis of 523 cases. AB - The paper reports a consecutive series of 523 patients undergoing abdominal aortic aneurysm surgery, paying particular attention to the cardiological risk factor. Coronary disease was present in 167 (31.9%) cases and the overall mortality rate was 1.7%: 5 cases (3%) in the group of coronary disease patients; 4 cases (1.2%) in the group of noncoronary disease patients. All fatal cardiac complications during the postoperative period occurred in those patients who presented coronary cardiopathies before surgery. The preoperative cardiological risk was therefore much greater and more significant in this group of patients. This risk factor should therefore be assessed prior to the operation in order to prepare the necessary medical or even surgical therapeutic measures. PMID- 1876447 TI - Circadian rhythm of sinoatrial conduction time assessed by 24 hours ECG monitoring. AB - SACT was evaluated in 50 subjects during 24 hours ECG monitoring. All of these subjects presented frequent atrial beats with no evidence of bradyarrhythmias. SACT was measured in accordance with Strauss' formula (SACT = P2P3 - P1P1/2). Twenty-four hours recording were divided in to 4 time intervals, 6 hour each, starting 7 o'clock. The SACT is higher during nighttime than during daytime. The phenomenon is, presumably, attributable to predominance of the para-sympathetic tone during the night. PMID- 1876448 TI - Abdominal aortic aneurysms surgery in over 75 years old patients. Experience in 142 cases treated between 1980-1989. AB - The paper describes the Authors' experience of abdominal aortic aneurysm surgery in over 75-year-old patients. One hundred and forty-two cases were operated over a 10-year period (1980-89). Seventy-two patients were treated electively and 70 underwent emergency surgery following rupture of the aneurysm. Operative mortality during elective surgery was comparable to that in younger patients, whereas the mortality rate during emergency surgery was notably higher than that in under 75-year-old patients. Follow-up confirmed that the life expectancy of operated patients is significantly better than that of patients with untreated abdominal aortic aneurysms. PMID- 1876449 TI - Effect of an inhibitor of PGE (flurbiprofen) on colony growth from normal and leukemic peripheral leukocytes in basal conditions and in presence of testosterone or cortisol. AB - The Authors have controlled the colony growth in coltures from peripheral leukocytes of normal subjects and from patients with CML and AML. The cultures were prepared on double agar layer in basal conditions and after adding flurbiprofen and/or cortisol and/or testosterone. The exam of the plates has shown a light similar stimulating activity on the growth of all substances separately considered, with and evidence ability of flurbiprofen of potentiate the action of the two hormones, both in coltures from normal and leukemic peripheral leukocyte CFU-GM. PMID- 1876450 TI - G.F.R. measuring with 99mTc-DTPA: limits in obstructive acute renal failure. AB - After a short introduction on the advantages and limits of G.F.R. determination with Ccr, the radioisotopic methods proposed by Schlegel and Gates for this parameter are described, and as well as ERPF and FF, without blood serial samples being necessary. In a severe renal failure case due to obstruction, the Authors have found a great mismatch in the results between the traditional methods and the radioisotopic ones. After the clinical case description, a possible explanation of this discrepancy is proposed: Schlegel and Gates' methods, which well correlate Ccr in chronic renal failure cases, in severe renal failure on obstructive basis, of recent onset, could not indicate the effective glomerular filtrate, but the nephronic mass, functionally blocked by the endocapsular hypertension secondary to the obstruction, but anatomically unaffected and so recoverable by a timely irradication of the obstruction. PMID- 1876451 TI - Copper in human seminal plasma. AB - One hundred and twenty five randomly selected semen samples revealed the range of copper in seminal plasma from 7.5 to 400 ug/dl. The metal had no statistical correlation with number of spermatozoa or with its percentage of motility. PMID- 1876452 TI - Multiple myeloma in L'Aquila and Avezzano, Italy, 1970-89. Changes in incidence rates, symptoms at diagnosis, and survival. AB - From 1970 to 1989, multiple myeloma was diagnosed in 184 residents in the counties of L'Aquila and Avezzano, two cities of the Region Abruzzo in Central Italy. The data were analysed for variations by sex, classes of age, urban and residence areas, symptoms and clinical stages at presentation, causes of death, and survival curves. The average annual incidence rate in the period 1970-89 was 5.8 per 100,000 residents. This increase in trend is statistically-significant (p less than 0.01). The average incidence was consistently higher among males, the age group 61-70 years old, and residents in urban areas for the decades 1970-79 and 1980-89. The increase in incidence rates of multiple myeloma was evident in all population categories, without significant differences (p greater than 0.05) in any evaluated class. The patients diagnosed in 1970-79 presented significantly (p less than 0.05) higher percentage of bone involvement at first diagnosis with respect to the patients diagnosed in 1980-89. A significant difference (p less than 0.05) was also observed in the clinical stage distribution. Patients from the 1980-89 decade survived for a significant (p less than 0.0001) longer period of time than the diagnosed between 1970-79. No differences (p greater than 0.05) were noted regarding causes of death. These results confirm the recent data of an increased incidence of multiple myeloma in the world. This trend could be due to an improvement in diagnosis and recording of multiple myeloma. On the other hand, environmental and occupational factors may play an important role in this increase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876453 TI - Two pregnancies in a Cushing's syndrome. Case report. AB - A case of patient with Cushing's syndrome due to an adrenal adenoma who conceived twice in the course of the disease is described. Pregnancy is known to be rare in these patients. When first seen she had some manifestations of Cushing's syndrome, but follow-up was lost prior to complete investigation. She conceived a few months later and gave birth to a 900 g premature liveborn infant. At the beginning of a second pregnancy, an adrenal adenoma was resected. The remainder of her pregnancy was uneventful and she delivered a normal fullterm 4 kg infant. Both children show normal physical and neurological development up to date. The patient presented herein illustrates the early diagnosis of Cushing's syndrome during pregnancy is extremely important, and early surgical treatment is indicated in order to avoid maternal and fetal complications. PMID- 1876454 TI - Bilateral popliteal artery entrapment syndrome. A case report and clinical considerations. AB - The authors report their experience in the management of a rare case of bilateral popliteal artery entrapment syndrome occurred to their observation. This unusual pathological entity, arising mostly in young subjects and unilaterally, in this case was bilateral and developed in a 51 years old patient. The clinical case is fully documented by multiple Echo-Doppler and arteriographic examinations which clearly demonstrate the peculiar characteristics of the disease. Finally the patient received a two stage surgical treatment with a good global result. The Authors stress the importance of a correct diagnostic approach to this unusual disease to avoid the possibility to misdiagnose it. PMID- 1876455 TI - The concomitance of renal artery stenosis and Conn's adenoma in a hypertensive woman. AB - A case of adrenal aldosterone-secreting adenoma concomitant with active renal artery stenosis in a hypertensive middle-aged woman is reported. The concomitance of the two lesions was previously reported in the literature only in five more reports, that are mentioned and commented here. This association is thought to be almost anecdotal, but some remarks must be done in order to rule out the risk of leaving an ignored lesion at the time of the definitive treatment. The widespread use of noninvasive imaging techniques is effective to find unsuspected adrenal adenoma in the presence of renovascular hypertensive disease, whereas unknown renal artery stenosis can be revealed by more aggressive diagnostic attitude, that is justified only in well selected cases of Conn's disease. PMID- 1876456 TI - A father and son with visceral leishmaniasis. A description of the pediatric case. AB - The paper reports a case of a 6-year-old boy affected by visceral leishmaniasis. In addition to clinical and anamnestic findings, diagnosis was made on the basis of the rapid increase in the titer of anti-Leishmania antibodies (16-fold), while the marrow smear was negative. A complete recovery was obtained using antimonial drugs. PMID- 1876457 TI - Noninvasive assessment of left ventricular function in asymptomatic diabetics and its relation to metabolic control and microangiopathy. AB - Fifty otherwise healthy patients with diabetes mellitus (37 males, 13 females; mean age: 53 +/- 10 years) of more than five year duration were compared with twenty six healthy age and sex matched controls. Detailed echocardiographic evaluation was done in all and systolic time intervals (STI) were measured. In diabetics, metabolic control and presence of microangiopathy were evaluated. PEP Index (patients: 146.23 +/- 17.04; controls: 121.99 +/- 5.15; p less than 0.001), PEP/LVET ratio (patients: 0.38 +/- 0.07; controls: 0.32 +/- 0.02; p less than 0.001), LVEF% (patients: 54.1 +/- 10.56; controls: 64.71 +/- 6.33; p less than 0.001), all were significantly altered in diabetics suggesting left ventricular dysfunction. The left ventricular posterior wall thickness (patients: 0.96 +/- 0.23 cm; controls: 0.85 +/- 0.12 cm; p less than 0.01) and interventricular septal thickness (patients: 1.2 +/- 0.24 cm; controls: 0.87 +/- 0.25 cm; p less than 0.001) in diastole were increased in diabetics. The PEPI correlated with day to-day control but not with chronic glycemic control of diabetes mellitus. The PEP/LVET was significantly increased in patients with severe, as compared to those with none or mild microangiopathy (p less than 0.05). Thus, significant left ventricular dysfunction is evident in asymptomatic, otherwise healthy diabetics. Both metabolic control and microangiopathy may be responsible for the abnormalities. PMID- 1876458 TI - The history of the calcaneal fracture. AB - The treatment of intra-articular calcaneal fractures has been a source of controversy in the past century. Major shifts in emphasis among four broad categories of therapy--no reduction, closed reduction, open reduction, and primary arthrodesis have occurred. The historical foundations of each of these treatments are traced to the present and related to modern approaches. The evolution of classification systems and developments in understanding the pathomechanisms of these fractures are also reviewed. According to several authors, modern treatment is making increasing use of open reduction after appropriate analysis and classification by computed tomography. PMID- 1876459 TI - Apophyseal fracture of the lumbar spine in adolescence. AB - A case of adolescent lumbar disc herniation with apophyseal fracture is reported. The patient, a 12-year-old boy, experienced sudden onset of pain during athletic activity. Examination revealed tenderness on palpation of the L-5 and S-1 spinous processes, straightening of the lumbar spine, and exquisite pain on 10 degrees of hyperextension. Straight leg raising, Lasegue's, and bowstring tests were all positive. Magnetic resonance imaging and computed tomography confirmed the diagnosis. Treatment included exercise, ibuprofen administration, and limitation of sports activity. At 23 months, the patient is symptom-free. A literature review of 20 cases with computed tomographic or myelographic diagnosis is presented, and conservative and surgical treatment programs are outlined. PMID- 1876460 TI - Gunshot wounds to the extremities. Experience of a level I trauma center. AB - Gunshot wounds to the extremities are more common today, largely because civilian handgun injuries have increased. Such injuries, which are usually caused by low velocity missiles, should be treated differently from those caused by high velocity (military) missiles. Bone involvement, including fractures and joint injuries, necessitates orthopaedic management. At the University of Medicine and Dentistry of New Jersey-New Jersey Medical School's (UMDNJ-NJMS) University Hospital, a level I trauma center, 44 gunshot wounds (32 lower-extremity and 12 upper-extremity) with orthopaedic complications were treated between January 1986 and December 1988. The protocol/questionnaire used by the UMDNJ-NJMS is presented here to assist the orthopaedic surgeon in the evaluation and treatment of these problematic injuries. PMID- 1876461 TI - Popliteal arterial injuries associated with fractures or dislocations about the knee as a result of blunt trauma. AB - A total of 73 patients with popliteal arterial injuries due to blunt trauma were treated at the Los Angeles County/University of Southern California Medical Center between January 1975 and January 1986. The injuries resulted from high energy trauma (70% were motor-vehicle-related), and were associated with a variety of fractures and dislocations about the knee. Forty-eight of the patients (66%) had open injuries, 27% of which became infected; the infection rate for all injuries was 22%. The average time from injury to anastomosis was 14.6 hours. The overall amputation rate in the series was 15%. Ten of the 11 amputations were associated with open, type III fractures. The amputation rate did not correlate with type of fracture, delay in diagnosis, or delay in surgery of up to 24 hours, but was directly related to the degree of soft-tissue trauma. PMID- 1876462 TI - Tips of the trade #37. Technique for reduction of shoulder dislocation. AB - A modification of the hippocratic technique for reduction of a dislocated shoulder is presented. This technique facilitates application of traction and rotation. PMID- 1876463 TI - Organism-specific antibody indices, the cerebrospinal fluid-immunoglobulin index and other tools: a clinician's guide to the etiologic diagnosis of central nervous system infection. PMID- 1876464 TI - Pseudomonas aeruginosa cellulitis and ecthyma gangrenosum in immunocompromised children. AB - Pseudomonas aeruginosa skin infections are generally considered to be secondary manifestations of disseminated disease. A retrospective analysis of all cases of P. aeruginosa skin infections seen at St. Jude Children's Research Hospital since 1962 revealed 16 episodes of the infection (ecthyma gangrenosum, 8 episodes, 7 patients; cellulitis, 8 episodes, 7 patients) in which blood cultures were uniformly negative for P. aeruginosa. All cases were identified while the patients were receiving ambulatory care. Five episodes developed while the patients' neutrophil counts were greater than 1 x 10(9) cells/liter. Eight patients had acute lymphoblastic leukemia, 2 had acute myeloid leukemia, 2 had aplastic anemia, 1 had transient agranulocytosis and 1 had cyclic neutropenia. There were no solid tumor patients. Although patients received different antibiotic combinations, all had resolutions of their lesions without fatal complications. Patients diagnosed as having cellulitis required a mean of 9.2 days of treatment with intravenous antibiotics, as compared with 17.8 days for those with ecthyma gangrenosum (P less than 0.05 by the Wilcoxon test). These observations show that P. aeruginosa skin infections can develop in the absence of bacteremia in immunocompromised children. PMID- 1876465 TI - Resolution of otitis media with effusion with the use of a stepped treatment regimen of trimethoprim-sulfamethoxazole and prednisone. AB - This double blind, placebo-controlled trial was designed to determine whether intervention with a stepped regimen of trimethoprim-sulfamethoxazole (TMP-SMX) and prednisone would prevent high risk children from developing chronic otitis media with effusion (OME) and recurrent acute otitis media. Forty-two children were enrolled, assigned to treatment with active drug or placebo and then examined at 2-week intervals. They received TMP-SMX (or placebo) during the first 2 weeks, TMP-SMX and prednisone (or placebo) during Weeks 3 and 4 for persistent OME and TMP-SMX (or placebo) for Weeks 5 and 6 if OME was still unresolved. After treatment 48% of active drug and 14% of placebo subjects resolved OME bilaterally (P less than 0.05). Active drug subjects also had fewer acute otitis media episodes than placebo subjects while receiving study treatment (P less than 0.01). Although this treatment regimen produced short term OME resolution, long term benefits were not demonstrated. PMID- 1876466 TI - Lack of association between neutropenia and the incidence of bacteremia associated with indwelling central venous catheters in febrile pediatric cancer patients. AB - To assess the incidence of bacteremia in pediatric cancer patients with indwelling central venous catheters with fever, we reviewed the records of all 67 such patients sequentially admitted during a 10-month period at our institution. There were a total of 140 episodes of fever in these 67 patients. In 55 of the episodes (39%) patients were nonneutropenic (absolute neutrophil count, greater than 500/mm3); 85 episodes (61%) were associated with neutropenia. Twenty-four percent of all episodes of fever in nonneutropenic patients were related to bacteremia vs. 9.5% of episodes of fever in the presence of neutropenia (P less than 0.05). When clinical evidence of an exit site infection was absent, the incidence of bacteremia in the neutropenic and nonneutropenic groups was similar (11% in the neutropenic group; 10% in the nonneutropenic group). We conclude that bacteremia is frequently observed in febrile pediatric cancer patients with indwelling venous catheters who are not neutropenic, particularly if there is clinical evidence of an exit site infection. Thus empiric antibiotic therapy is warranted in all pediatric oncology patients with indwelling catheters who develop fever. PMID- 1876467 TI - Astroviruses as a cause of nosocomial outbreaks of infant diarrhea. AB - During a 16-month study period at a children's hospital, 32 children developed nosocomial gastroenteritis caused by astroviruses. Twenty-five of these occurred during 2 epidemic outbreaks in medical and surgical infants' wards. From the community, 13 confirmed cases were admitted during the study period. Both community-acquired and nosocomial cases occurred during autumn, winter and early spring. The attack rates during outbreaks ranged between 7 and 62% and were highest among children with underlying gastrointestinal diseases. Diarrhea and vomiting were the most common clinical manifestations. The median duration of symptoms was 4 days and that of virus excretion was 5 days. Hospital infection with astroviruses is common and usually affects children less than 2 years of age. The probable mode of transmission is spread via contaminated hands. PMID- 1876468 TI - Advances and problems in the diagnosis of human immunodeficiency virus infection in infants. PMID- 1876469 TI - Cervical neurenteric fistula causing recurrent meningitis in Klippel-Feil sequence: case report and literature review. PMID- 1876470 TI - Office diagnosis of neonatal chlamydial conjunctivitis. PMID- 1876471 TI - Axillary vs. rectal temperatures in ambulatory and hospitalized children. PMID- 1876472 TI - Measles giant cell pneumonia in a child with human immunodeficiency virus infection. PMID- 1876473 TI - Neonatal retropharyngeal abscess. PMID- 1876474 TI - Purulent pericarditis in a neonate. PMID- 1876475 TI - Multisystem disease in an eight-year-old boy. PMID- 1876476 TI - Utility of beta-2-microglobulin concentrations as a marker of infection with human immunodeficiency virus. PMID- 1876477 TI - Multidrug resistant Salmonella typhi. PMID- 1876478 TI - Management of infants with suspected neonatal sepsis and a positive urine latex agglutination test for group B streptococci. PMID- 1876479 TI - Non-exercising muscle metabolism during exercise. AB - Glycogen decrements have been observed in non-exercising muscles during exercise. We therefore investigated whether the degraded glycogen was retained within the muscle in the form of glycolytic intermediates, or whether it was effluxed from the non-exercising muscles. For these studies a suspension harness was used to unload the hindlimb muscles at rest and during exercise [McDermott et al. (1987) J Appl Physiol 63:1275-1283]. Concentrations of glycogen and glycolytic intermediates glucose 6-phosphate, fructose 6-phosphate, fructose 1,6 bisphosphate, glycerol 3-phosphate, and lactate) were measured in non-exercising and exercising muscles (soleus, plantaris, red and white gastrocnemius) during a 90-min exercise about 15 m/min, 8% grade). On-line electromyographic analysis showed that the contractile activity in the non-exercising muscles was markedly lower than in the exercising muscles. Similar decrements in muscle glycogen levels were observed in both the non-exercising and exercising muscles at the end of the 90-min, exercise bout (P less than 0.05), despite significantly different activity profiles. An increase in tissue lactate concentrations occurred in both non-exercising and exercising muscle (P less than 0.05), although only slight changes in the glycolytic intermediates occurred. The sum total of all the accumulated glycolytic intermediates and lactate (converted to glucosyl units) in the non-exercising muscles only accounted for a small fraction of the glycogen degraded (approximately 15%-28%). We conclude that the metabolism of glycogen is enhanced in non-exercising muscle, and that glycogen utilization is uncoupled from the energetic demands of the muscle. Furthermore, the glycogen mobilized in non-exercising muscle is not retained within the muscle in other metabolite pools.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876480 TI - Tedisamil blocks single large-conductance Ca(2+)-activated K+ channels in membrane patches from smooth muscle cells of the guinea-pig portal vein. AB - Enzymatically dispersed smooth muscle cells of the guinea-pig portal vein were studied by the patch-clamp technique. They were found to have Ca(2+)-dependent K+ channels with the typical properties of the "BK" channel, i.e. a reversal potential at the calculated equilibrium potential for K+ ions, a striking voltage dependence, and a conductance of approximately 200 pS ([K+]o 50 mM, [K+]i 150 mM, positive patch potentials). Tedisamil, a new bradycardic agent with an inhibitory action on K+ currents in heart muscle, reduced the open probability of the BK channels concentration-dependently (1-100 microM) when applied at the cytosolic side of membrane inside-out patches. At 100 microM [Ca2+]i, the IC50 of tedisamil was 13.8 microM (mean, n = 5). Tedisamil increased the frequency of channel closures, and reduced the mean duration of openings from 8 ms to less than 1 ms, while the mean duration of closures within bursts (1-2 ms) was not altered. Tedisamil did not affect long closures (greater than 160 ms) between bursts, either. The mean time of residence of tedisamil at the BK channel was estimated to be 1-2 ms. Hence, tedisamil, in comparison to the "slow" blocker Ba2+ and the "fast" blocker tetraethylammonium, holds the position of an "intermediate" K+ channel blocker. PMID- 1876481 TI - What does TnCDANZ fluorescence reveal about the thin filament state? AB - Fluorescence of skinned psoas fibres reconstituted with the troponin C subunit labelled with the fluorescent probe dansylaziridine (TnCDANZ) increases upon activation with Ca2+. This fluorescence enhancement is due to Ca2+ binding to the Ca(2+)-specific binding sites of TnCDANZ and attachment of cross-bridges to the actin filament. We found that approximately 20% of the enhanced fluorescence signal derived from Ca2+ binding to TnCDANZ and 80% from cross-bridge attachment during maximal activation. Furthermore we studied the effects of different cross bridge states on TnCDANZ fluorescence. "Weakly" bound, non-force-generating cross bridge states (pCa 8, low ionic strength) and rigor cross-bridges revealed similar effects on the TnCDANZ fluorescence. "Strongly" attached, force generating states, however, increased fluorescence to the greatest extent. These results suggests a complex system of reciprocal couplings between TnC and different attached cross-bridge states. Cooling or increase of inorganic phosphate decreased isometric force but hardly decreased fluorescence, suggesting the accumulation of attached cross-bridge states with low tension output. PMID- 1876482 TI - Contraluminal p-aminohippurate transport in the proximal tubule of the rat kidney. VIII. Transport of corticosteroids. AB - Using the stop-flow peritubular capillary microperfusion method contraluminal transport of corticosteroids was investigated (a) by determining the inhibitory potency (apparent Ki values) of these compounds against p-aminohippurate (PAH), dicarboxylate (succinate) and sulphate transport and (b) by measuring the transport rate of radiolabelled corticosteroids and its inhibition by probenecid. Progesterone did not inhibit contraluminal PAH influx but its 17 alpha- and 6 beta-hydroxy derivatives inhibited with an app. Ki of 0.36 mmol/l. Introduction of an OH group in position 21 of progesterone, to yield 11-deoxycorticosterone, augments the inhibitory potency considerably (app. Ki, PAH of 0.07 mmol/l). Acetylation of the OH-group in position 21 of 11-deoxycorticosterone, introduction of an additional hydroxy group in position 17 alpha to yield 11 deoxycortisol or in position 11 to yield corticosterone brings the app. Ki, PAH back again into the range of 0.2-0.4 mmol/l. Acetylation of corticosterone or introduction of a third OH group to yield cortisol does not change the inhibitory potency, but, omission of the 21-OH group or addition of an OH group in the 6 beta position reduces or abolishes it. Cortisol and its derivatives prednisolone, dexamethasone and cortisone exert similar inhibitory potencies (app. Ki, PAH 0.12 0.27 mmol/l). But again, omission of the 21-OH group in cortisone or addition of a 6 beta-OH group reduces or even abolishes the inhibitory potency against PAH transport. The interaction of corticosterone was not changed when 11 beta, 18 epoxy ring (aldosterone) was formed. On the other hand, the interaction was considerably augmented if the 11-hydroxy group was changed to an oxo group in 11 dehydrocorticosterone (app. Ki, PAH 0.02 mmol/l). When the A ring of corticosterone is saturated and reduced to 3 alpha, 11 beta tetrahydrocorticosterone the inhibitory potency is not changed very much. But if more than four OH or oxo groups are on the pregnane skeleton or if the OH in position 21 is missing, the inhibitory potency decreases drastically (app. Ki, PAH 0.7-1.7 mmol/l). Introduction of a 21-ester sulphate into corticosterone, cortisol and cortisone does not change app. Ki, PAH very much. Glucuronidation, however, reduces it (app. Ki, PAH approximately 1.2 mmol/l). None of the tested corticosteroids interacts, in concentrations applicable, with dicarboxylate transport and only the sulphate esters interact with sulphate transport. Radiolabelled cortisol, D-aldosterone, 11-dehydrocorticosterone, and corticosterone are rapidly transported into proximal tubular cells. With the latter three compounds no sign of saturation and no transport inhibition with probenecid could be seen.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1876483 TI - Transport of L-leucine hydroxy analogue and L-lactate in rabbit small-intestinal brush-border membrane vesicles. AB - Substitution of the alpha-amino group of amino acids by hydroxyl groups yields hydroxy analogues (HA), which have been ascribed beneficial effects in nitrogen sparing diets for uremic patients. In this study, intestinal uptake of L-leucine HA (L-LeuHA) and L-lactate into rabbit jejunal brush-border membrane vesicles was investigated. An inward-directed H+ or Na+ gradient stimulated uptake of both labelled substrates in a voltage-clamped assay. The H+ gradient was the major driving force of uptake as compared with the Na+ gradient, and it led to a transient accumulation of both L-LeuHA and L-lactate. The proton ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) reduced the initial H(+) gradient-driven uptake rates of both substrates, but was without effect on Na(+) gradient-driven uptakes. The H(+)-gradient-driven L-LeuHA uptake was saturable (apparent Kt = 15.4 mM). Alpha-HA of L-leucine, L-isoleucine, L-valine, D leucine, D-valine or L-lactate inhibited the H(+)-gradient-driven L-LeuHA or L lactate uptakes whereas free branched-chain amino acids had no effect. Preloading the vesicles with one of the L- or D-HA of branched-chain amino acids or with L lactate stimulated tracer L-LeuHA and also tracer L-lactate uptakes in the presence of a H+ gradient. It is concluded that H(+)-gradient-driven transport of L- and D-stereoisomeric HA of branched-chain amino acids as well as of L-lactate across rabbit intestinal brush-border membranes is mediated by the same carrier. Furthermore, there exists a Na+ gradient-driven L-lactate transport system in the rabbit intestinal brush-border membrane. PMID- 1876484 TI - Microelectrode study of voltage-dependent Ba2+ and Cs+ block of apical K+ channels in the skin of Rana temporaria. AB - The blockage of the apical K+ channels in frog species Rana temporaria by Ba2+ and Cs+ is strongly voltage-dependent. The interaction of both blockers with the K+ channels was studied by recording relations between the K+ currents (IK) and the transepithelial and intracellular potential. Mucosal Ba2+ and Cs+ depress IK, hyperpolarize the cell and induce pronounced nonlinearities in the current/voltage (I/V) relations. The nonlinearities are caused by the voltage dependent interaction of Ba2+ and Cs+ with the binding site. Consequently, the apical membrane resistance not only depends on the blocker concentration but also on the apical membrane potential. Also the fractional resistance, fRa, and the voltage divider ratio, fVa, will change with blocker concentration and voltage. Owing to this non-ohmic behaviour, measurements of fVa in the presence of Ba2+ deviate markedly from the expected fRa values. The inhibitory effect of Ba2+ and Cs+ was analysed at different transepithelial and apical membrane voltages. The relation between the Michaelis-Menten constants and the voltage could be fitted with equations based on Eyring rate theory with the assumption of a single binding site. With this model we calculated the relative electrical position of the binding site for the blocker (delta), referred to the extracellular side of the channel. We obtained for Ba2+, delta = 0.34 +/- 0.05 and for Cs+, delta = 0.81 +/- 0.01. Comparison of the results from apical and transepithelial I/V relations demonstrates that the analysis of the transepithelial data provides overestimated values of the Hill coefficient and results in an underestimation of delta. PMID- 1876485 TI - Two types of fast K+ channels in rat myelinated nerve fibres and their sensitivity to dendrotoxin. AB - The effect of dendrotoxin (DTX), a component of the venom of the Eastern green mamba snake, Dendroaspis angusticeps, on K+ currents in rat myelinated nerve fibres was studied in voltage clamp experiments, immunocytochemistry and binding experiments. The analysis of K+ tail currents in 160 mM KCl solution revealed that K+ channels with slow gating kinetics predominate in the intact node of Ranvier. These slow K+ channels were not blocked by DTX. Intact nerve fibres additionally showed fast K+ tail currents of small amplitude which could be blocked by DTX. After enzymatic demyelination with pronase, fast K+ currents of large amplitude appeared. Analysis of the non-monotonous voltage dependence of the fast K+ conductance and the partial pharmacological block by DTX suggest the presence of two subtypes of fast K+ channels in rat nerve fibres similar to the Kf1 and Kf2 channels previously described in the frog and toad node of Ranvier. The DTX concentration required for 50% inhibition (IC50) for the Kf1 component was 8 nM. The IC50 of the blocked Kf2 component was the same as that for Kf1, but the Kf2 component was only partially blocked (about 50%). In contrast to frog nerve, these two fast K+ channel subtypes are located predominantly in the paranodal region. Immunocytochemical staining experiments with DTX using the peroxidase-antiperoxidase technique confirmed the electrophysiological data. In intact nodes, either no staining or only slight staining in some fibres was found. After demyelination, extensive staining of paranodal and internodal regions occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876486 TI - Widespread synchronous [Ca2+]i oscillations due to bursting electrical activity in single pancreatic islets. AB - Pancreatic beta cells, tightly organized in the islet of Langerhans, secrete insulin in response to glucose in a calcium-dependent manner. The calcium input required for this secretory activity is thought to be provided by an oscillatory electrical activity occurring in the form of "bursts" of calcium action potentials. The previous observation that islet intracellular free Ca2+ levels undergo spontaneous oscillations in the presence of glucose, together with the fact that islet cells are coupled through gap junctions, hinted at a highly effective co-ordination between individual islet cells. Through the use of simultaneous recordings of intracellular calcium and membrane potential it is now reported that the islet calcium waves are synchronized with the beta cell bursting electrical activity. This observation suggests that each calcium wave is due to Ca2+ entering the cells during a depolarized phase of electrical activity. Moreover, fura-2 fluorescence image analysis indicates that calcium oscillations occur synchronously across the whole islet tissue. The maximal phase shift between oscillations occurring in different islet cells is estimated as 2 s. This highly co-ordinated oscillatory calcium signalling system may underlie pulsatile insulin secretion and the islet behaviour as a secretory "syncytium". Since increasing glucose concentration lengthens calcium wave and burst duration without significantly affecting wave amplitude, we further propose that it is the fractional time at an enhanced Ca2+ level, rather than its amplitude, that encodes for the primary response of insulin-secreting cells to fuel secretagogues. PMID- 1876487 TI - Gating currents of inactivating and non-inactivating potassium channels expressed in Xenopus oocytes. AB - The Xenopus oocyte expression system in combination with patch-clamp techniques allows the measurement of ionic currents from a single class of genetically engineered ion channels. Ionic currents in the nanoampere range from oocytes injected with cRNA, corresponding to potassium channels, can be recorded in the inside-out patch configuration. These recordings have a high time resolution at low background noise. Substitution of impermeant ions for potassium and blocking of the channel conductance with tetraethylammonium allows the recording of potassium gating currents, Ig, which is hampered in natural excitable cells by the simultaneous presence of sodium channels and a variety of different potassium channels. The "on" transients, Ig(on), are fast and can have amplitudes of up to several tens of pA. Upon repolarization to -100 mV after small depolarizations, "off" gating currents, Ig(off)g, which reverse most of the "on" charge displacement, Q(on), within 1 ms, are readily observed. However, this fast recovery of the gating charge is drastically reduced upon increasing the amplitude of the depolarizing pulse. In contrast to sodium channels, this temporary charge immobilization is complete within a few milliseconds at positive membrane potentials. Furthermore, there seems to be no direct correlation between charge immobilization and inactivation because the same phenomenon occurs for channels that do not inactivate. PMID- 1876488 TI - Baccalaureate and master's degree programs in nursing accredited by the NLN 1991 92. PMID- 1876490 TI - Criteria and guidelines for the evaluation of associate degree programs in nursing. PMID- 1876489 TI - State-approved schools of nursing R.N. 1991. PMID- 1876491 TI - Recognizing and assisting the impaired nurse: recommendations for nurse managers. AB - The impaired nurse places the client, her/himself, and all members of the healthcare community at risk. As members of the nursing profession, the priority of all nurses is to protect clients and adhere to professional standards of practice. In light of the statistics validating increased abuse by nursing professionals, the author believes that Peer Assistance Programs and Employee Assistance Programs are necessary and should be supported. To do less is to continue a "conspiracy of silence". PMID- 1876492 TI - Alzheimer's disease: diary of a caregiver. PMID- 1876493 TI - Autonomy: part of the nursing role? PMID- 1876494 TI - Said another way. Seeing the world through different lenses. PMID- 1876495 TI - One year later: evaluating a changing delivery system. AB - One year after the introduction of primary nursing on four medical and surgical units in the tertiary hospital, a 23-item survey was distributed to primary and associate nurses on these units to evaluate the nurses' perceptions of the status of this change in nursing care delivery. Lewin's theory of change provided direction for evaluation of the change. The survey assessed improvements in patient care, changes in nursing practice, and interactions with other disciplines. The majority of nurses surveyed reported that patient care had improved under primary nursing; 100% of the primary nurses agreed that care had improved. The nurses identified continuity of care, communications, and awareness of patient problems as specific areas of improvement. They also identified improved interactions with many members of the healthcare team; the greatest were with dietitians, social workers, and physicians. The authors reported both positive and negative perceptions of how practice had changed under primary nursing. Results from the survey provided suggestions for continued support for staff nurses in this change in nursing care delivery within the studied facility, and suggested the need for future assessment and further evaluation. PMID- 1876496 TI - Intervention strategies for environmental control. PMID- 1876497 TI - The lady with the lamp. PMID- 1876498 TI - A health environment: nurses concern. PMID- 1876499 TI - Nursing negligence. PMID- 1876500 TI - Nursing and HIV/AIDS: focus on counselling. PMID- 1876501 TI - Difficulties encountered in transport of the critically ill child. AB - A prospective survey of difficulties encountered in 100 pediatric emergency interhospital transfers was undertaken to identify needs for education of referring doctors and of transport service staff, as well as weaknesses in the organization of a pediatric emergency transport service (PETS). Such obstacles to smooth retrieval included administrative difficulties, mistakes in management, and unresolved acute severe physiologic derangements in the child. Three hundred ninety-four problems were found: 24% were preventable by improved education of referring doctors; these included unrecognized needs for ventilatory support, added oxygen, chest x-ray or nasogastric tube, and difficulties with airway selection, placement, and care. Twenty-eight percent were preventable by better PETS organization, education, protocols, or telephone checklists; examples include equipment problems and clinical derangements unrecognized at referral. Difficulties owing to conditions of transport (eg. vibration, dysbarism, and air turbulence) were uncommon (five percent of patients). Regular reviews of performance of all PET services, combined with measures to educate referring doctors, can improve patient outcome. PMID- 1876502 TI - Complaints and compliments in the pediatric emergency department. AB - We conducted an analysis of all communications received from patients or their families by the director of a pediatric emergency department over a three-year period, during which approximately 150,000 visits occurred. Communications were characterized as complaint or compliment and subclassified by type: waiting time, staff attitude, quality of medical care, and billing. Chi 2 analysis was used to identify factors that predisposed to complaint or compliment and to identify the subtype. After quality-of-care issues, complaints stemmed most often from billing issues or waiting time for care for nonurgent disorders (especially medical problems), while complimentary letters most frequently addressed staff attitude and quality of care. The problems that we identified might be addressed by providing families improved access to non-emergency department care sources, education regarding the role of an emergency department, and better explanation of billing procedures during the registration process. Additionally, our findings serve as a reminder that many parents appreciate the care given to their children, particularly for life-threatening emergencies. PMID- 1876503 TI - Effects of albumin on ionized calcium in vitro. AB - Human serum albumin is used to treat hypoproteinemia in neonates or used as a volume expander. We tested the hypothesis that the addition of human serum albumin to neonatal serum decreases the serum ionized calcium (iCa) concentration. Concentrated human serum albumin was added to 12 placental and cord serum samples to reach seven incremental concentrations from 0 to 20.0 g/L. Serum iCa concentration decreased significantly with the addition of serum albumin. From multiple regression analysis, the effect of albumin addition on serum iCa concentration had more marked effects at high baseline albumin or low baseline Ca concentrations. From this in vitro study, we speculate that fast infusion of albumin in human neonates has the potential for acutely lowering serum iCa concentration. PMID- 1876504 TI - The effect of diazepam enema on the rectal mucosa of rats. AB - The use of undiluted intravenous diazepam solution administered as an enema has been recommended for the acute management of seizures when intravenous access cannot be obtained. It is well absorbed, rapidly effective, and generally accepted as being safe when used in this manner. The effect of intravenous diazepam solution on the rectal mucosa has not been studied. This study demonstrates that there are no acute changes in the rectal mucosa of adult rats after administration of 10 to 20 times the recommended human dose. PMID- 1876505 TI - Herpetic gingivostomatitis associated with a petechial skin rash. PMID- 1876506 TI - In-flight esophageal variceal bleeding en route for liver transplantation: a case report and review of the literature. AB - Esophageal variceal bleeding owing to portal hypertension is a potential threat in pediatric patients awaiting liver transplantation. We report a case of a three year-old boy with severe congenital hepatic fibrosis, Caroli's disease, and portal hypertension who developed a life-threatening variceal hemorrhage for the first time in his life during commercial air transport to a liver transplantation center. Factors precipitating variceal bleeding are discussed, particularly those resulting from changes in altitude. It is recommended that prophylactic treatment for variceal bleeding be at least considered in children awaiting liver transplantation prior to prolonged air transportation. Because of differences in capabilities of treatment providers in various locales, and because there are as yet no conclusive data, the treatment of choice must be decided on an individual basis. Equipment for treating in-flight hemorrhage should be available. PMID- 1876507 TI - Pediatric chin injury: occult condylar fractures of the mandible. AB - The diagnosis of occult mandibular condylar fractures in children is often missed or delayed on initial examination when children present with a laceration to the chin. A clue to the diagnosis of this type of skeletal injury to the mandible is the knowledge of a commonly occurring pattern of injury associated with chin trauma. Chin laceration, fracture of the parasymphyseal region near the chin, and fracture of the condyles are often concomitant injuries of the mandible. This article reviews three case reports of children who sustained a chin laceration, fracture in the region near the chin, and fracture to the mandibular condyles secondary to chin trauma that were not initially diagnosed on clinical examination. PMID- 1876508 TI - Toxicity with dextromethorphan-containing preparations: a literature review and report of two additional cases. AB - Dextromethorphan-containing cold/cough preparations are frequently prescribed and bought over the counter for use in children. Although generally considered safe, dextromethorphan has been shown to cause CNS side effects, including hyperexcitability, increased muscle tone, and ataxia. Two deaths have been reported with intentional dextromethorphan overdose. A literature review, brief review of pharmacology, and report of two cases of adverse reactions to dextromethorphan-containing preparations are presented. PMID- 1876509 TI - Lung injury resulting from a nonaccidental crush injury to the chest. AB - A six-week-old infant presented with rib trauma and a lung contusion from a nonaccidental compressive chest injury. He developed an illness consistent with diffuse alveolar damage, which worsened over 26 hours. This was complicated by a pneumomediastinum, and the patient recovered with conservative management. The value of isotope bone scanning in addition to x-rays is discussed. Nonaccidental injury should be considered in the differential diagnosis of a pulmonary contusion. PMID- 1876510 TI - Pain and decreased movement of left arm. PMID- 1876511 TI - Congenital syphilis: an emerging emergency. AB - Is a condition such as congenital syphilis within the purview of pediatric emergency medicine? The following case histories would suggest that it is. PMID- 1876512 TI - Cross-sectional echocardiographic measurements of right ventricular size and growth in patients with pulmonary atresia and intact ventricular septum. AB - Fifteen patients with pulmonary atresia or critical pulmonary stenosis and intact ventricular septum were studied. All were operated on in the neonatal period, with valvotomy or a systemic to pulmonary arterial shunt, or both. In 12 patients, right ventricular to pulmonary arterial communication was established in the neonatal period. In three patients, only systemic to pulmonary arterial shunts were constructed. Six patients died. The median follow-up period for the surviving patients was 64 months (range, 12-87 months). Right and left atrial and ventricular dimensions and areas, the tricuspid annular diameter, and the cross sectional area of the aortic root were measured in cross-sectional echocardiograms from the neonatal period, at the age of 1 year, and at the latest clinical follow-up. A classification of right ventricular morphology was made, based on identification of the inlet, the trabecular, and the outlet parts. Most of the patients had hypoplastic right ventricles at birth but at the latest follow-up, seven of nine surviving patients had right ventricles in the normal range. Right ventricular growth was better in patients who were given a right ventricular to pulmonary arterial communication in the neonatal period and those with complete right ventricular anatomy. The patients who died had severely hypoplastic right ventricles and small tricuspid valves. PMID- 1876513 TI - Left ventricular myocardial mass determined by cross-sectional echocardiography in normal newborns, infants, and children. AB - Changes in left ventricular muscle mass may be an important diagnostic or prognostic finding in children with congenital heart defects, but there are no data on normal mass as determined by cross-sectional echocardiography (CSE) in children. Fourteen newborns, 12 infants, and 69 children (1.5-17 years old) with a structurally normal heart were studied. End-diastolic and end-systolic volume and mass were calculated from biplane-paired echocardiographic imaging planes apical two-chamber and apical four-chamber views-using both an area/length and a Simpson's rule geometric method. Data were compared with M-mode measurements. There was a good correlation between area/length and Simpson's rule method [r = 0.94, standard error (SE) 4 g/m2]. To validate the measurements, interobserver data were gathered and end-diastolic and end-systolic mass measurements were compared. Interobserver variability for the measurements on the echocardiographic recordings was low at 4.8%; for end-diastolic mass the correlation between two observers was r = 0.99 (SE 3.3 g/m2) and for end-systolic mass r = 0.97 (SE 7.6 g/m2). Correlation between end-systolic and end-diastolic mass was acceptable (r = 0.88, SE 5.9 g/m2) for the CSE mass determination, but poor for the M-mode measurements (r = 0.51, SE 20.2 g/m2). Similarly, correlation between M-mode mass and mass estimated by CSE was poor, at r = 0.58 for end-diastolic and r = 0.094 for end-systolic mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876514 TI - Cardiomyopathy in glycogen-storage disease type III: clinical and echographic study of 18 patients. AB - Cardiac examinations were performed on 18 patients with glycogen-storage disease (GSD) type III. Clinical examination was always normal and the electrocardiograms revealed nonspecific data. Similarly, serum muscular enzyme activities were not useful in indicating the presence of cardiomyopathy. Echocardiographic evidence of myocardiopathy was found in five of the 16 children studied (mean age, 9.5 years). Echocardiographic parameters remained stable during the follow-up period (at least 3 years). The other 11 children had no echocardiographic evidence of cardiomyopathy. No relationship was found between peripheral myopathy and cardiomyopathy. All patients with GSD type III should be regularly investigated by echocardiography in respect of their cardiac muscle status. PMID- 1876515 TI - Reassessment of usefulness of porcine heterografts in mitral position in children. AB - The use of porcine heterograft valves in children is restricted because of valve calcification and dysfunction at follow-up. Because of inability to monitor the anticoagulant status or of desire of some teenage girls to get married and get pregnant, several pediatric patients received porcine heterografts. The purpose of this paper is to examine the issue of heterografts in children, based on our experience with children and adolescents, aged 1 to 20 years, who underwent left heart valve replacement during a 7-year period ending April 1985. Ninety-four percent of the lesions were rheumatic in origin, 4% congenital, and 2% infectious. Of 168 mitral valves replaced, 54 (32%) were porcine heterografts and 114 (68%) were mechanical valves. These were divided into four groups, based on type of valve implanted and age at implantation: mechanical (M), age greater than 15 years (M greater than 15), 49 cases; heterografts (H) age greater than 15 years (H greater than 15), 34 cases; mechanical, age less than or equal to 15 years (M less than or equal to 15), 65 cases; and heterografts, age less than or equal to 15 years (H less than or equal to 15), 20 cases. None of the patients with heterografts received anticoagulation. Five-year actuarial valve survival was 86% for M greater than 15, 96% for H greater than 15, 82% for M less than or equal to 15, and 60% for H less than or equal to 15. The respective 9-year valve survival was 86%, 72%, 75%, and 18%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876516 TI - Open heart surgery in children of Jehovah's Witnesses: extreme hemodilution on cardiopulmonary bypass. AB - Between January 1979 and July 1989, 15 children of Jehovah's Witnesses underwent corrective open surgery for congenital heart disease (CHD) on cardiopulmonary bypass (CPB). Ages ranged from 1.5-17 years and body weight from 9.1-63 kg, with five patients weighing less than 15 kg. Eight children were cyanotic, and two of them had had previous thoracic operations. All operations were performed in moderate to deep hypothermia using a modified version of isovolemic hemodilution with bloodless priming technique of extracorporeal circulation. Mean hematocrit levels decreased from 47.3% (36.9-70%) to 34.6% (27.2-49.1%) after hemodilution, and then to 17.9% (10.5-25.6%) during bypass. They increased again to 34.1% (24.4 50%) at the end of the operation and to 33.4% (25.1-40%) on day 12. All intra- and postoperative hematocrit levels were significantly lower (p less than 0.001). There was one postoperative death, not related to the technique. Our results demonstrate that bloodless cardiac surgery on bypass is feasible in children as shown in this special group of children of Jehovah's Witnesses. Knowing the risks of homologous blood transfusion this technique should be used more extensively in the future. PMID- 1876517 TI - Balloon dilatation of a stenosed aortic homograft conduit following repair of the common arterial trunk. AB - An 8-year-old boy, who underwent surgical correction of a common arterial trunk at the age of 10 months, developed stenosis of the 15-mm aortic homograft. Chest x-ray demonstrated calcification of the homograft, and at cardiac catheterization there was a 57 mmHg gradient across the conduit. He underwent balloon dilatation using a 15-mm balloon catheter. After four inflations at a pressure of 5.5 atm, the gradient decreased to 34 mmHg. Six months later he had a Doppler-estimated gradient of 38 mmHg. PMID- 1876518 TI - Unique variant of partial anomalous pulmonary venous connection with intact atrial septum. AB - Partial anomalous pulmonary venous connections (PAPVCs) are rare in association with an intact atrial septum. However, the diagnosis should be considered in patients with otherwise unexplained findings of left-to-right shunt and right heart enlargement. An unusual variant is presented, which we considered unsuitable for operative repair, based on findings at catheterization. Developmental, hemodynamic, and surgical considerations are discussed. PMID- 1876519 TI - Patent ductus venosus. AB - A patent ductus venosus has been reported on only two previous occasions. Both involved adults who presented with recurrent bouts of encephalopathy. We present the case of an infant with complex congenital heart disease and multiple other abnormalities, in whom a patent ductus venosus was an incidental finding at necropsy. The etiology of this condition and the options for management are discussed. PMID- 1876520 TI - Successful modified Fontan procedure in an adolescent after left pneumonectomy. AB - We performed a Waterston's anastomosis on a patient with complicated tricuspid atresia when she was two months of age. At age 14 years she required left pneumonectomy for massive, idiopathic hemoptysis. Four months after the pneumonectomy we substituted a modified Fontan anastomosis for the Waterston anastomosis. Restudy when she was 17 years of age showed continued satisfactory function. PMID- 1876521 TI - Tetralogy of Fallot with severe pulmonary valvar stenosis and pulmonary vascular sling (anomalous origin of the left pulmonary artery from the right pulmonary artery). AB - A patient with the rare combination of tetralogy of Fallot with severe pulmonary valvar stenosis and pulmonary vascular sling is presented. The limitations imposed by pulmonary artery hypoplasia on the display of pulmonary vascular sling by conventional imaging techniques are discussed. PMID- 1876522 TI - Associated occurrence of persistent truncus arteriosus and asplenia. AB - An infant with persistent truncus arteriosus associated with splenic agenesis and the asplenia syndrome is reported, including clinical, echocardiographic and autopsy findings. To the authors' knowledge this association has not been previously reported. PMID- 1876523 TI - Franz Buchner. January 20, 1895--March 9, 1991. PMID- 1876524 TI - Histopathologic diagnosis of pigmented lesions of the skin. AB - The present review deals with the histopathologic diagnosis of the commonest pigmented lesions of the skin with emphasis on melanocytic tumors. The discussed entities are systematized in pigmented lesions with and without an increase in the number of melanocytes, i.e. melanocytic hyperplasia, and in those that actually are melanocytic neoplasias. Histopathological, ultrastructural, and immunohistochemical features of relevance for the differential diagnosis are discussed in depth. One section is dedicated to the immunohistochemical markers of melanocytic lesions, the other one to the electron microscopy of malignant melanoma. Neoplasms simulating malignant melanoma and the less frequent variants of this tumor are also discussed. The diagnosis of pigmented lesions of the skin represents one of the most frequent and difficult challenges in dermatopathology, and useful clues for the differential diagnosis, especially of melanocytic dysplasias and neoplasias, are presented in the present article. PMID- 1876525 TI - Metastatic tumors to the female breast. An autopsy study of 12 cases. AB - Twelve cases of metastatic tumors to the female breast are reported. Ten of them were incidentally discovered at autopsy; two cases were diagnosed ante mortem but one was misinterpreted as primary. The patients' mean age was 58 years. The metastasizing tumors included cutaneous malignant melanoma (four cases); ovarian, renal and gastric adenocarcinoma (two cases each); and individual cases of pulmonary and pancreatic carcinoma. The patients with melanoma were younger than the others (49.7 vs. 62.7 years). The results of the present study indicate that breast metastases, although rare, are not exceptional especially in large autopsy series. Their recognition in surgical material would result in more adequate treatment against the primary tumor, thereby avoiding unnecessary radical surgery to the breast. PMID- 1876526 TI - Distribution of basement membrane-associated heparan sulfate proteoglycan in idiopathic and AIDS-associated Kaposi's sarcoma. AB - In the present study we analyzed the immunohistochemical distribution of different major basement membrane (BM) components with special emphasis on the BM associated heparan sulfate proteoglycan (HSPG) in early and late stages of Kaposi's sarcoma (KS), both of idiopathic and AIDS-associated origin. In early KS all BM components tested were found surrounding the small clefts of tumour vessels. Heparan sulfate proteoglycan showed the weakest and often fragmented pattern of staining. In the late, nodular sarcomatous form of KS individual tumour cells were surrounded by a BM composed of collagen IV, laminin and fibronectin, while heparan sulfate proteoglycan was not detectable in most cases. Neither between idiopathic and AIDS-associated KS nor between cutaneous and visceral lesions were significant differences in the staining pattern. Our findings of a rather selective expression of various BM-components and the known distribution in normal blood and lymphatic capillaries raises the hypothesis that KS-cells may be derived from cells of lymphaticovenous differentiation. PMID- 1876527 TI - Mycosis fungoides and Sezary syndrome in Japan. Clinicopathologic study of 107 autopsy cases. AB - We reviewed 111 clinical and pathological materials of patients who had been entered as mycosis fungoides (MF) or Sezary syndrome (SS) in the Annuals of the Pathological Autopsy Cases in Japan during the 29-year-period since the Annuals' inception in 1958. One hundred and seven patients were classified. Of these, 64 were in Group 1 (mycosis fungoides, MF), 23 in Group II (Sezary syndrome, SS), and 20 in Group III (non-Hodgkin's lymphoma, NHL). The clinicopathologic features of Groups I and II (MF, SS) were similar to those of cutaneous T cell lymphoma (CTCL) in Europe and the United States. Those of Group III (NHL) were indistinguishable from primary cutaneous non-Hodgkin's lymphoma. It was suggested that some patients with adult T cell leukemia/lymphoma (ATLL) with skin lesions used to be misdiagnosed as MF or SS in earlier years when ATLL was still unknown. It was concluded that CTCL in Japan has clinicopathologic features quite like those of CTCL in Europe and the United States and that they are probably the same disease. PMID- 1876528 TI - Distinction of mesothelioma from carcinoma in pleural effusions. An immunocytochemical study on routinely processed cytoblock preparations. AB - The study was designed to find out whether the commercially available antibodies BMA 130 c, BMA 120, V 9, KL 1, B 72.3 TAG, HEA 125 and Ber-EP 4 would be of help in distinguishing carcinomas from a mesothelial process (mesothelioma/pleuritis) in pleural effusion specimens routinely processed by the cytoblock method. All of the 20 carcinomas included in the study but also 19 of the 20 mesotheliomas expressed cytokeratin (KL 1), whereas vimentin expression was found in 7 of the 20 carcinomas and 19 of the 20 mesotheliomas. 19 of the 20 carcinomas reacted with the epithelial markers B 72.3 and HEA 125, and 18 of them with Ber-EP 4. In contrast, only a few of the 20 mesotheliomas showed a weak reaction to these markers (1 with HEA 125, 2 with B 72.3, and 3 with Ber-EP 4). BMA-130 c was detected in 10/20 carcinomas but in none of the mesotheliomas. BMA-120 was observed in the effusions from 17/20 mesotheliomas and in cover cells which had undergone reactive changes, but also in 2 cases of ovarian carcinoma. The results show that reaction to the "epithelial markers" B 72.3, HEA 125 and Ber-EP 4 is strongly indicative of carcinoma and not of mesothelioma, whereas a positive reaction with the antibody BMA-120 in the absence of reaction to the epithelial markers makes a mesothelial process very likely. However, immunocytochemical distinction cannot be made as yet between mesothelioma cells and pleuritic cells. If simultaneous positivity for BMA-120 and an "epithelial marker" in a pleural effusion is observed the primary tumor could be an ovarian carcinoma. PMID- 1876529 TI - Immunohistochemical estrogen receptor assessment in hyperplastic, neoplastic, and physiologic endometria. AB - Endometrial hyperplasias and some endometrial carcinomas arise in a setting of estrogen excess. Steroid hormones interact with cells via specific receptors; assessing receptor levels may indicate a tissue's potential for interaction with that hormone. To examine estrogen receptor (ER) levels in endometrial hyperplasia, endometrial carcinoma, and physiologically cycling endometrium, an immunohistochemical technique utilizing a monoclonal anti-estrophilin (estrogen receptor) antibody was applied to formalin-fixed, paraffin-embedded tissue. In complex hyperplasia and grade I adenocarcinoma, the mean percentages of epithelial cells demonstrating nuclear staining for ER was mildly decreased compared to proliferative endometrium. A trend was noted toward less ER staining in atypical hyperplasia compared to non-atypical complex hyperplasia. ER varied with physiologic cycling of the endometrium. ER was also present in atrophic endometrium, myometrium, adenomyosis, and leiomyomata. Immunohistochemistry permits localization of ER and is a useful technique in ER assessment of endometrial hyperplasias and carcinomas. PMID- 1876530 TI - Prognostic significance of accessory cells and lymphocytes in nasopharyngeal carcinoma. AB - Forty-five consecutive biopsy specimens of nasopharyngeal carcinoma (NPC) and 10 biopsies of healthy nasopharyngeal mucosa obtained from non-cancer patients were investigated by immunohistochemical methods. Monoclonal (B2, T1) and policlonal antibodies (against S-100 protein and lysozyme) with reference to infiltrating lymphocytes and accessory cells (monocytic/macrophagic and dendritic cells) were used. Variable population densities of dendritic cells (S100+) were demonstrated in 22 out of the 45 cases (49%) of NPC; the distribution of these cells was typically within the cancer nests. Monocytic/macrophagic cells (Lys+) were found along the tumor margins and interspersed among the tumor cells in 14 out of 45 (31%) cases. No significant statistical correlation between density of accessory cells and histological type of NPC (classified according to Micheau criteria) was found. Cases with a moderate to marked density of dendritic and monocytic/macrophagic cells survived longer than those with a slight one (mean survival of 63%, 67% and 29%, 27% respectively). In NPC tissues T-lymphocyte infiltration was prevalent. In contrast, B cells were numerous and T cells rare in normal control tissues. The intensity of T-cell infiltration was significantly high in cases with a marked density of S-100+ cells, according to the ability of these cells to present antigens to sensitized T-cells. This study suggests a prognostic significance for reactive cells infiltrating NPC, which means longer survival for cases associated with marked infiltration density of accessory cells. PMID- 1876531 TI - Atypical mitoses in colorectal adenomas. AB - The frequency of spontaneously occurring mitotic figures, the proportion atypical mitoses and spatial position (vertical, oblique or horizontal) of metaphasial plates were studied in 62 specimens: 47 with colorectal adenomas, and 15 with chronic ulcerative colitis (control cases). The characteristics of the atypical mitoses at pro-phase, pro-metaphase, metaphase, anaphase and telophase were defined and illustrated. The results indicated that atypical mitoses occurred in 8.9% in control patients, in 37.2% of the specimens tubular adenomas having low grade dysplasia, in 80.8% in tubular adenomas with high-grade dysplasia, in 68.5% of villous adenomas with low-grade dysplasia and in 65.5% of villous adenomas with high-grade dysplasia. For villous adenomas with high-grade dysplasia having invasive growth, 81.3% of atypical mitoses was recorded. Oblique or horizontal metaphasial plates were present in 8% of the metaphases in control cases but in as much as 25% in tubular adenomas with low-grade dysplasia, in 37% of those with high-grade dysplasia, in 42% for villous adenomas with low-grade dysplasia, in 56% for those with high-grade dysplasia and in 53% for villous adenomas with invasive growth. The classification of the various degrees of dysplasia is at present done by the characteristic of the dysplastic cells at interphase. This paper demonstrates that qualitative and quantitative morphological alterations of the mitotic apparatus takes place in the various histological types of colorectal adenomas. Perhaps both the number of atypical mitoses and the spatial position of the mitoses should be registered in attempts to shed more light on the biological behaviour of adenomatous lesions of the colorectal mucosa. PMID- 1876532 TI - Adenosquamous carcinoma of the esophagus. A case report. AB - A case of adenosquamous carcinoma of the esophagus is presented. This carcinoma is a typical neoplasm of the upper aerodigestive tract almost exclusively originating in squamous epithelium in continuity with minor salivary glands. It is a very rare tumor in the esophagus, and is often diagnosed as mucoepidermoid carcinoma. The differential diagnosis between them is important due to the better prognosis of the last entity. The histology and electron microscopy is described and the literature is reviewed. PMID- 1876533 TI - Third meeting of the European Association for Haematopathology, Wurzburg, 7-11 October 1990. PMID- 1876534 TI - Morphometric and stereological study of the glandular epithelium of the lateral prostate of the intact and castrated guinea pig. AB - The glandular epithelium of the lateral prostate of the guinea pig was described within the framework of a morphometric model in terms of relative densities and absolute dimensions. A combination of direct measurement and point and intersection counting techniques was used. The quantitative data generated in the intact animals were compared with those of castrated controls. Castration was accompanied by a significant decrease in height of the glandular epithelium and in sizes of secretory and basal cells and their corresponding nuclei. On a per cell basis, significant decreases in total volume and surface area of granular endoplasmic reticulum were detected after castration. This was accompanied by a significant reduction in the total volume of Golgi cisternae. The total volume, surface area, and number of highly electron-dense and clear granules decreased significantly compared with the intact control animals. However, no significant changes in these parameters of low electron-dense granules were found. Significant reductions in the total volume and surface area of condensing granules, lysosomes, and mitochondria, but not their number, were detected. The average sizes of condensing granules, secretory granules, lysosomes, and mitochondria were decreased significantly after castration. The present study showed that the alterations in the secretory function of the secretory cells of the lateral prostate was reflected by the quantitative changes in granular endoplasmic reticulum, Golgi complexes, and secretory granules on a per cell basis. The data generated in the present study will serve as a baseline for further studies of the lateral prostate of the guinea pig. PMID- 1876535 TI - Family aggregation of cancer of the prostate in Quebec: the tip of the iceberg. AB - Cancer of the prostate is one of the most common cancers among males in North America. Although some causative factors have been suggested by several surveys, the etiology of this common cancer is poorly understood. In a case-control study of prostatic cancer in Greater Montreal, 21 of 140 patients with prostatic cancer (15.0%) gave a positive family history of the same cancer, as compared with two cases among 101 (2.0%) population-based controls. This indicates about an eightfold difference in occurrence of cancer of the prostate among first-degree family members of the case group with an odds ratio (OR) of 8.7 and 95% CI, 2.00 38.17. In this report we present the pedigrees of three families (two cases and one control) with four pathologically confirmed cases of cancer of the prostate in each family. This data suggest that a familial predisposition to prostatic cancer may become apparent in later decades of life. In these family aggregations, in addition to the genetic factors, environmental factors may also play an important role in the etiology of the same cancer among family members. PMID- 1876536 TI - Density-dependent regulation of epidermal growth factor receptor expression in DU 145 human prostate cancer cells. AB - Androgen-independent prostate cancer cells may rely on an autocrine loop for growth stimulation, and have been shown to express both the epidermal growth factor receptor (EGFR) and its stimulatory ligands. We have shown here that DU 145 prostate cancer cells have a decreased amount of EGFR in confluent cultures when compared to levels seen in subconfluent cultures. This down-regulation of EGFR numbers is not due to cell proliferation or nutrient depletion, but can be correlated only with whether cell-cell contact exists throughout the culture. This is reminiscent of the situation existing in some tumors whereby EGFR expression is higher in cells at the invading margins of the tumor. PMID- 1876537 TI - In vivo assay for conversion of testosterone to dihydrotestosterone by rat prostatic steroid 5 alpha-reductase and comparison of two inhibitors. AB - An in vivo assay for steroid 5 alpha-reductase in rat ventral prostate has been developed and used to compare the inhibitory activity of N,N-diethyl-4-methyl-3 oxo-4-aza-5 alpha-androstane-17 beta-carboxamide (4-MA) and 6-methylene-4 pregnene-3,20-dione (LY207320). Immature rats (70-80 g) received test compounds 30 min prior to s.c. injection of [3H]-T. The rats were sacrificed 30 min later and the ventral prostates were analyzed for [3H]-T metabolites. Intraprostatic [3H]-T and [3H]-DHT reached peak levels within 5 min after injection of [3H]-T and declined to about 25% of peak levels after 2 hr. 4-MA was a very potent inhibitor of [3H]-DHT formation with an estimated IC50 of 0.2 mg/kg. LY207320, an inhibitor of 5 alpha-reductase in vitro, was weakly active in vivo and did not achieve greater than 45% inhibition at high doses (greater than 200 mg/kg, s.c.). Tissue uptake of [3H]-T was also inhibited by LY207320, which may contribute to its inhibitory activity on accessory sex organ growth in the rat. PMID- 1876538 TI - Distribution of Langerhans cells and HLA class II molecules in prostatic carcinomas of different histopathological grade. AB - We have investigated Langerhans cell (LC) distribution in 38 prostatic carcinomas, of various degrees of differentiation, by immunohistochemistry with a polyclonal anti-S-100 serum, furthermore evaluating the expression of HLA class II-DR by neoplastic cells using a monoclonal antibody (MoAb) that reacts with a monomorphic determinant in formalin-fixed paraffin-embedded tissue. Antiserum to S-100 protein identified LCs mostly in carcinomas ranging from grade 1 to grade 2, while LCs were inconspicuous in grade 4 and virtually absent in grade 5 cancers. Moreover, sections stained with the anti -HLA-DR MoAb displayed an immunoreactivity, both cytoplasmic and apical, especially confined to neoplastic glands of low grade (1-2) carcinomas. Although we did not find a direct correlation between the two parameters under investigation and lymphoid infiltrate, we were able to document an increased number of HLA class II-positive interstitial cells in low-grade carcinomas, corresponding mostly to macrophages. Our results indicate that LC number is inversely correlated to the histopathological grade and directly to the expression of HLA class II-DR molecules by tumor cells; we believe that this might be important in understanding the more favorable biological behavior of low-grade prostate carcinomas as opposed to the higher grades, since LCs and HLA class II molecules may provide a means of eliciting the immune response, both LCs and epithelial cells expressing HLA class II molecules being capable of direct antigen presentation to immune cells. In this context macrophages might play a primary role in controlling tumor progression. To the best of our knowledge this is the first time that an attempt is made to correlate LCs and HLA class II expression to histopathological grading of prostatic carcinomas. We would also suggest that the presence of LCs and HLA class II molecules, either singly or in combination, in carcinoma of the prostate represents a good prognostic indicator, being constantly associated with the clinically less aggressive low-grade tumors. The evaluation of these two parameters might prove useful in the assessment of intermediate grades where no valid histologic criteria have been found to predict the clinical course of the disease. PMID- 1876539 TI - Survival of Salmonella typhimurium ATCC 14028 on the surface of chicken legs or in mechanically deboned chicken meat gamma irradiated in air or vacuum at temperatures of -20 to +20 C. AB - Response-surface methodology was used to develop predictive equations for the response of Salmonella typhimurium ATCC 14028 on the surface of chicken legs or within mechanically deboned chicken meat (MDCM) to the effects of gamma radiation doses of 0 to 3.60 kGy (100 krad = 1 kGy) at temperatures of -20 to +20 C in air or vacuum. A streptomycin-resistant mutant was used in these studies to allow accurate estimations of the surviving salmonellae in the presence of residual normal flora. This strain has been demonstrated to have no significant shift in its biological properties nor in its resistance to ionizing radiation. The response of S. typhimurium to gamma radiation was similar on both chicken legs and MDCM. The radiation was significantly more lethal to the bacterial cells at temperatures above freezing. The response-surface equations developed from the studies predict that the number of viable cells per gram of MDCM or per square centimeter of the surface of chicken legs would be reduced approximately 2.8 to 5.1 log units at 0 C by radiation doses within the range of 1.5 to 3.0 kGy. The results of the present studies are similar to those obtained previously with sterile mechanically deboned chicken meat. PMID- 1876540 TI - Research note: the effects of darkling beetles on broiler performance. AB - Six polyvinylchlorine pipe darkling beetle traps were placed in 20 commercial broiler production facilities, and the relative level of beetle infestation was determined from weekly sampling during 4 wk of the growout period. The average number of beetles found at each facility was compared with the following production parameters: mortality, feed conversion, condemnation rate, and production cost. In the 20 commercial broiler flocks evaluated, the level of darkling beetles within the facility was not related to any of the production parameters measured. PMID- 1876541 TI - Research note: lack of effect of a live yeast culture on broiler breeder and progeny performance. AB - Broiler breeders were fed corn and soybean diets containing 0, .1, .3, or .5% of a live yeast culture from 21 through 64 wk of age. In addition to assessing various breeder reproductive variables, chicks from each treatment level were grown to 17 days of age at 30, 40, 50, and 60 wk of breeder age. With the exception of a significant decrease in fertility at the .3% level, there were no effects on broiler breeder or progeny performance. PMID- 1876542 TI - Research note: effect of tetracycline hydrochloride and oxytetracycline hydrochloride given via drinking water on early mortality of broiler chicks from twenty-eight-week-old dams. AB - The effect of tetracycline HCl and oxytetracycline HCl on early mortality in straight-run Peterson x Hubbard cross broiler chicks from 28-wk-old dams was studied. Treatments consisted of a sham-treated control, and groups treated with a tetracycline either HCl (25 mg/454 g of BW per day) or an oxytetracycline HCl (14.6 mg/454 g of BW per day). Each group was treated via the drinking water for the first 5 days after hatching. There were 24 replications per treatment with 54 chicks each. Birds were maintained at a density of 622.5 cm2 per chick. Chicks treated with tetracycline HCl and oxytetracycline HCl had significantly (P less than .05) improved livability when compared with the sham-treated controls both at 2 and 6 wk of age (1.00 and .83 versus 1.79 at 2 wk, and 2.79 and 3.29 versus 4.29% mortality at 6 wk, respectively). No significant differences in mortality were observed between tetracycline HCl-treated chicks and oxytetracycline HCl treated chicks. At the end of the 6-wk trial, no differences between treatments were seen in the productive performance of the broilers. The observed differences in livability at 6 wk of age could increase the number of saleable broilers by 10 to 15 thousand per million chicks placed. PMID- 1876543 TI - Genotype, feeding regimen, and diet interactions in meat chickens. 1. Growth, organ size, and feed utilization. AB - Allomorphic growth of organs and feed utilization were measured in cockerels from two meat lines known to differ in growth potential under alternate-day and daily feeding of diets differing in nutrient density. The faster growing line consumed more feed and utilized feed more efficiently than the slower growing line. Relative weights of heart and all segments of the gastrointestinal tract except the esophagus were smaller in the faster than in the slower growing line whereas breast, thigh, and drumstick were greater for the faster than the slower growing line. These patterns existed regardless of diet. In contrast, line by feeding regimen interactions were noted for most traits; the faster growing line was influenced more by restricted feeding than the slower growing line. Thus, the practice of selecting individuals in a restricted-feeding environment when commercial stocks have feed available to them at all times may be faulty. Although the alternate-day feeding regimen improved feed efficiency, results indicated that full benefit of feed restriction would be realized by feeding a diet higher in nutrient density. PMID- 1876544 TI - Genotype, feeding regimen, and diet interactions in meat chickens. 2. Feeding behavior. AB - Feeding behaviors were compared for males from two lines of meat chickens differing in growth potential fed lower and higher density diets ad libitum either daily or on alternate days. Males from the faster growing line ate and drank more often but stood and rested less often than those from the slower growing line. Rate of feed intake per unit BW was, however, similar for both lines. Greater crop and lower intestinal contents of the faster growing line suggested a higher feed intake and storage ability. Even though males fed the lower energy diet initially consumed similar amounts of ME on days of food restoration, by 24 h they lagged behind those fed the higher energy diet, suggesting capacity of the gastrointestinal tract (GIT) to be a limiting factor in energy consumption. At older ages, chicks fed the different diets had similar GIT contents, suggesting that excessive eating and less resting observed for males fed the lower density diet contributed to their poorer energy utilization. On the day of feed restoration, males fed on alternate days ate and stood more often and had poorer GIT clearance than those with feed continuously made accessible to them. PMID- 1876545 TI - Genotype, feeding regimen, and diet interactions in meat chickens. 3. General fitness. AB - Several fitness traits were measured in males from two meat lines fed diets differing in nutrient density ad libitum daily or on alternate days. Criteria of evaluation were antibody response to SRBC, blood heterophil:lymphocyte ratios, incidence of leg deformities, and resistance to Escherichia coli inoculation. Males from the heavier line had lower antibody titers to SRBC inoculation than those of the lighter line. Diets, feeding regimens, and interactions among them did not influence response to SRBC. Lines, diets, feeding regimens, and interactions among them were not significant for heterophil:lymphocyte ratios. Chicks fed daily had a higher incidence of leg deformities than those fed on alternate days. There were no differences between lines or diets, nor were interactions significant. Interactions were present between main variables for response to E. coli inoculation whether the measure was initial weight loss, recovery, or lesion scores, demonstrating the complexity of genotype environmental relationships in resistance to this infectious agent. PMID- 1876546 TI - Effects of imperfect albinism (sal-s) on egg production in two lines of chickens. AB - Two trials were conducted with two different lines of chickens to determine whether a gene for sex-linked imperfect albinism (sal-s) affected various egg production traits. In a line with relatively good egg production, sexual maturity was delayed for albino compared with nonalbino hens, but overall egg production by albinos was higher. The increased production resulted in eggs with reduced yolk and shell weights. Albumen weights were not affected, and because the eggs from albinos were smaller, Haugh unit scores were higher. In another trial, sexual maturity of hens of a heavy line was not affected by the genotype, but these hens did not receive controlled lighting during the growing period. Egg production curves of these hens were very similar to those seen in the first trial. The laying house mortality rates were not affected by the sal-s gene, despite several periods of high environmental temperature. These trials suggest that sal-s could be used in a sex-linked cross of commercial layers or broiler breeders. PMID- 1876547 TI - Sex-linked and maternal effects on growth in chickens. AB - A study was designed to estimate the contribution of various types of genetic variation in growth of chickens using populations that widely differed in growth rate. Populations tested included a commercially developed sire line (CM), a fertility-selected, broiler-type line (FS), and the pureline Jersey Giant (JG). A full set of F1 crosses and purelines of both sexes was used to estimate the following genetic effects: heterosis due to the autosomes, heterosis due to the sex chromosomes, average line effects, maternal effects, and additive sex linkage. Average line effects were highly significant beyond hatching for both body weight and shank length, with rank-order CM greater than FS, which was greater than JG. Significant differences between the sexes within a line were observed for CM and JG line effects, confirming the existence of sex-linked factors. There was no average heterosis or sex-by-heterosis interaction for growth-related traits, but specific heterosis was frequently significant. Maternal effects were sporadic and generally of little importance beyond hatching. Additive sex linkage, however, was highly significant and influenced body weight beyond hatching. These data indicate that the primary advantages in increasing growth via cross-breeding in chickens comes from average line effects and additive sex linkage. Heterosis and maternal effects can influence performance, especially in specific crosses, but these effects appear to be sporadic and of less importance than sex linkage. PMID- 1876548 TI - Genetic correlations among growth, feed, and carcass traits of broiler sire and dam populations. AB - Genetic correlations based on sire variance and covariance components were estimated for broiler traits. Data were collected from various selected and control strains of sire and dam populations during five generations of selection. Results of analyses of variance for each of the strains within generations and populations were pooled across strains and generations. Correlations between body and carcass weights were all above .8. Weight gain (WG) had similar correlations with these traits with the exception of body weight at 28 days (.57 in site and .69 in dam populations). Body and carcass weights and WG had high correlations with feed consumption (FC) (greater than .7); however, values for feed efficiency (FE) varied: -.58, -.23 for 28-day body weight; -.17, .16 for 42-day body weight; .25, .43 for WG; and .53 in the dam population for carcass weight. Correlations of body and carcass weights and WG with abdominal fat weight (AFW) and percentage (AFP) were generally small to moderate with values being about half as large for AFP as for AFW. Feed consumption and FE were negatively correlated (-.51, -.22) in both populations. In the dam population, FC was positively correlated with AFW and AFP (.42, .55) but FE was negatively correlated with these traits (-.41, .70). Abdominal fat weight and AFP were highly correlated (.99, .97). Values tended to be similar not only for these populations but also for this and other studies. Simultaneous genetic improvement of growth rate, FE and carcass leanness is feasible in broilers. Selection for WG, FE, and AFP should be effective. PMID- 1876549 TI - Serological evidence for major histocompatibility complex (B complex) antigens in broilers selected for humoral immune response. AB - Genetic selection for early humoral immune responsiveness against two simultaneous antigens, namely, heat-killed Escherichia coli and Newcastle disease virus vaccine (NDV), was performed in a heterogenic population of broiler chickens. The humoral immune response was measured prior to 24 days of age, depending on the vaccine. Chicks were divided into two populations according to their antibody response: a population of high responders to both antigens and a population of low responders. After four generations of selection, a significant difference was observed in the immune response of the two populations, and therefore, an attempt was made to identify possible differences in the segregation of major histocompatibility complex genes. Using alloantisera prepared in B-congenic White Leghorn, the high responders exhibited a high percentage of chickens having erythrocytes agglutinated with B5 antisera, and the low responders exhibited a high percentage of chicks with erythrocytes agglutinated with B15 and B19 antisera. The B13 antisera agglutinated cells of similar proportions of chickens in the two populations. A random commercial broiler flock was screened with the antisera, and correlation was high between B haplotype and antibody level to E. coli following vaccination. The present work indicated the possibility of a direct association between the genetic characteristics represented in the B complex and humoral antibody response in a broiler population. PMID- 1876550 TI - Effect of the MN t(1;4) translocation on some economic traits of the chicken. AB - The F2 progeny from an original mating between chickens that were carriers of the MN t(1;4) chromosome translocation and the inbred WI-ES line were compared to determine if the translocation had any effect on selected economic traits. Homozygous translocation (TT), heterozygous translocation (TN), and karyotypically normal (NN) individuals were compared. Traits analyzed were body weight at 8, 18, 39, and 55 wk of age; shell deformation; Haugh units; egg weights at 32 and 55 wk of age; sexual maturity; egg production; and male fecundity. The TT group had greater body weights at 39 and 55 wk than the TN and NN groups, and at 55 wk the TN group was heavier than NN group. Shell deformation was greater for TT birds at 32 wk. At 32 wk, Haugh units of the TT and TN birds, and the TN and NN birds were not significantly different. The TT eggs were heavier than the TN eggs at 32 wk, which in turn were heavier than the NN eggs. Sexual maturity was reached in the order NN, TN, then TT. Eggs from TT males had the lowest fertility and highest percentage of late dead embryos. There were increased early deaths among embryos from heterozygous males. An unexplained higher number of pips among embryos from normal males was noted. No differences were noted among any other traits in either sex. Results suggest that this translocation may have some effect on production traits. PMID- 1876551 TI - Genetic association of selection for increased leg muscle and increased shank diameter with body composition and walking ability. AB - Body compositions of a randombred control population (RBC2), a line selected for increased 16-wk BW (F), a line selected for increased shank diameter (FL), and a line selected for increased leg muscle mass (FM) were compared at 16 wk of age. The F line originated from the RBC2 population and the FL and FM lines were developed as sublines of the F line. The F and FL lines were developed through mass selection of BW and shank width, respectively. The FM line was developed through family selection for leg muscle mass. Selection for BW in the F line has resulted in an increase in the proportion of breast muscle and a decrease in the relative amount of leg bone in comparison with the RBC2 population. Selection for increased shank width in the FL line has increased not only shank weight but has produced concomitant increases in the weight of the tibiotarsal and femur bones. Although FL line has also shown a correlated increase in BW in association with increases in shank width the increase in leg bone weight was relatively greater than the increase in BW. Therefore, the relative weights of leg bones in the FL line increased such that they were more similar to the RBC2 population than to the F line. Although the amount of leg muscle increased slightly in the FM line, the relative proportion of leg muscle did not increase significantly. The selection program used was probably ineffective in increasing the proportion of leg muscle because of the high percentage (low selection intensity) of families selected and small family size for estimating family means.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876552 TI - The effect of different levels of relative humidity and air movement on litter conditions, ammonia levels, growth, and carcass quality for broiler chickens. AB - An experiment using 4,800 commercial broiler males (Ross x Ross) was conducted in 12 climatic chambers. Three levels of relative humidity (RH) (45, 40, to 80, and 75%) and two levels of internal air circulation (7.7 to 9.9 and 17.8 to 24.5 cm/s), with each level replicated and, therefore, forming a 3 x 2 x 2 factorial arrangement of treatments, arrangement of treatments, were imposed as the main effects. Broilers were group weighed and feed efficiencies calculated at 14, 28, and 42 days of age. Percentage dry matter of the litter and a subjective evaluation of general litter conditions (moisture and caking) were scored weekly, with the percentage nitrogen and total quality of litter produced in each chamber measured at the conclusion of the study. Ammonia levels were measured in each chamber every second day. A sample of birds (36) from each chamber was processed at 42 days and scored for litter spots and ammonia burns on the breast and for the incidence and severity of twisted legs, crooked toes, and infected and calloused hocks and foot pads. Mean body weight was significantly greater (32 g) at 42 days of age in birds exposed to 45% RH compared with the two higher regimens of RH. Both the incidence and severity of ammonia burns on the breast and infected foot pads were significantly higher with 75 versus 45% RH. Increases in RH significantly increased caking and litter moisture and reduced the percentage of dry matter and the percentage of nitrogen found in the litter. Ammonia levels were more variable but generally increased with increases in RH. The two levels of air movement within the chambers produced less influence on the environment than RH, although the scores for both litter moisture and caking were significantly lower with increased levels of internal air circulation. PMID- 1876553 TI - The effect of feed intake on body temperature and water consumption of male broilers during heat exposure. AB - Two trials were conducted to study the effect of feed intake on rectal temperature and water consumption of acclimated and unacclimated broilers during heat exposure. Male broiler chicks, 100 per trial, were raised as one group to 29 days for Trial 1 and 36 days for Trial 2. The birds were moved to environmental chambers and 50 per trial were acclimated by being subjected to 3 consecutive days of 24 C, 35 C, 24 C cyclic temperature. After acclimation, the birds were exposed to a linear change in temperature from 24 to 41 C over 3 h with a constant 10 C dewpoint, starting at 0800 h on Day 34 for Trial 1 and on Day 41 for Trial 2. The feeding schedule for the day of the heat exposure was as follows. For the feed group, feed was removed from the birds at 0400 h and placed back at 0700 h. For the no feed group, feed was removed at 0700 h. At 0800 h, feed was removed from all birds but water was accessible throughout the heat exposure. Acclimated and unacclimated birds given access to feed for 1 h before a heat exposure consumed 60 and 50 mL of water per broiler, respectively, during the heat exposure. However, for broilers not receiving feed, the water consumption was 58 and 30 mL per broiler, respectively. Acclimated and unacclimated broilers given access to feed had similar body temperatures, but the acclimated broilers not receiving feed had a significantly lower ending rectal temperature than the unacclimated group. PMID- 1876554 TI - The influence of egg sequence position on fertility, embryo viability, and embryo weight in broiler breeders. AB - A study was undertaken to determine whether fertility, early embryo viability, and the weight of the egg, shell, and embryo are influenced by the position of an egg in a laying sequence. One hundred and three Indian River broiler breeder hens were housed individually in cages at 21 wk of age. Beginning at 43 wk of age, each hen was inseminated once per week, with 50 microL of fresh undiluted pooled semen from Indian River broiler breeder males. Beginning at 45 wk of age, and for the following 45 days, all eggs laid were collected. Eggs were collected hourly for 8 h after "lights on" and a final daily collection was made 14 h after lights on. Each egg was classified as "first-of-sequence" or "subsequent". Eggs were weighed and placed in a forced-air incubator twice per week. After 168 h of incubation, the eggs were removed from the incubator, weighed and assessed for fertility and embryo viability status. The embryo was also weighed. Shell weight was recorded after 3 to 4 days of air drying. Egg weight was significantly greater in first-of-sequence compared with subsequent eggs. First-of-sequence eggs exhibited significantly smaller Day 7 embryos (on a percentage basis), lower shell weight (on a percentage basis), and significantly less egg weight loss during the 7 day incubation period (absolute and percentage basis) than did subsequent eggs on a sequence. Least squares (LS) means for fertility did not differ significantly between first (87.02%) and subsequent (89.56%) eggs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876555 TI - Feed consumption of egg strain pullets at onset of lay. AB - An experiment was conducted to investigate the performance of four strains of commercial egg type pullets (A, B, C, and D) from 19 to 30 wk of age. The feed consumption differences during this period as well as feed consumption patterns 10 days prior to and after the first oviposition were of special interest. Two hundred and sixty-four birds (66 birds per strain) were fed a diet formulated to contain 2,750 kcal/kg ME, 17% CP, and 3.4% calcium. Results show that the average age to the first egg and percentage of hen-day egg production were not significantly different among the four strains of birds. However, egg weights of Strain A and C birds were significantly heavier than those of the Strain B and D birds. The birds from Strains B and D had significantly lower body weight than Strain A birds at the end of 18 wk, but body weights were not significantly different at the end of 30 wk. Feed intake per bird per day of pullets from Strains A and C was generally higher than that of those from Strains B and D in the first and second 4-wk period. Some of the consumption differences were significant. Feed intake in the third period (27 to 30 wk) was similar for the four strains of birds. Although different strains showed different feed consumption patterns around the first oviposition, all strains showed a drop on the day of the first oviposition. When the strains were combined, feed consumption was lower on that day than during the 8 days prior to the first oviposition. PMID- 1876556 TI - Effects of type of cage front and feed trough partitions on productivity and ingestive, agonistic, and fearful behaviors of egg-type hens. AB - Two groups of White Leghorn pullets reared in floor pens were used to study the effects on performance and behavior in cages of horizontal wire cage fronts with and without feed trough partitions (HP and H, respectively) and vertical wire cage fronts with and without feed trough partitions (VP and V, respectively). In Experiment 1, hens in HP and VP cages consumed more (P less than .05) feed than hens in either H or V cages. This greater feed consumption combined with similar egg production resulted in significantly poorer feed conversion (P less than .05) for hens in VP cages. Hens in HP cages had fewer drinking bouts (P less than .05) and an intermediate amount of feeding time. Hens in H, V, and VP cages did not differ significantly in number of drinking bouts and feeding times. There were differences in feeding location preferences among treatments (P less than .05) but not within treatments. In Experiment 2, effects of horizontal (H) and vertical (V) wire cage fronts were examined to determine their effects on productivity and fearful behavior. Hens in H cages had better feather scores (P less than .05) than hens in V cages. Type of cage front had no significant effects on age at sexual maturity, egg production, mortality rate, average egg weight, and body weight. PMID- 1876557 TI - Reproductive performance of artificially inseminated hens receiving saline drinking water. AB - Laying hens were selected at random and placed in individual cages in a commercial type layer shed. One hundred hens received town water and one hundred received town water supplemented with 2 g NaCl/L. Half the hens on each water treatment were inseminated every 7 days with mixed semen collected from six cockerels of a commercial table egg strain maintained on town water. The remaining hens were inseminated with semen from six cockerels receiving town water supplemented with 2 g NaCl/L. Eggs were collected and stored at 12 C over a 7-day period before eggs with defective shells were identified and removed. All remaining eggs were incubated and candled at 7 and 18 days of incubation to detect infertile eggs and embryonic deaths. Data from six consecutive hatches were analyzed. The incidence of eggs with defective shells doubled in hens receiving the saline drinking water. These hens had a significantly (twofold) higher incidence of embryonic deaths and a significantly lower (13%) hatchability of fertile eggs. For every 100 eggs laid the numbers of settable eggs and chicks hatched were significantly reduced in hens receiving the saline drinking water. The saline water reduced the numbers hatched by 20% for every 100 eggs laid. The water treatment given to the cockerels had little effect on reproductive performance. PMID- 1876558 TI - Use of a most probable number method modified with a deoxyribonucleic probe to monitor control by food preservatives of natural Salmonella contamination in animal meat meals. AB - A most probable number (MPN) technique using a DNA probe was developed for determination of Salmonella in naturally contaminated meat meals. The method eliminated the need for 180 selective plates and 75 selective tubes and saved 27 h when compared with a traditional technique; yet it still yielded identical MPN of Salmonella per 100 g in five naturally contaminated samples. The method was used to monitor the effect of a commercial food preservative (Sal Curb) at 0, .25, .50, 1.0, and 2.0% in meat meals with initial contaminations of 1,100, 93, or 7 MPN organisms/100 g. The preservative greatly reduced MPN in the 1,100 and 93 MPN samples in a time and dose-dependent manner, but in the sample with 7 MPN organisms/100 g of material, it resulted in 0 MPN organisms per 100 g after 24 h at all levels tested. PMID- 1876559 TI - Effect of coccidiosis on plasma epinephrine and norepinephrine levels in turkey poults. AB - Plasma epinephrine, norepinephrine, and glucose levels were measured in 3- to 4 wk-old turkey poults that had been infected with the coccidium Eimeria adenoeides. When measured at 6 days postinoculation, the acute stage of the infection, the epinephrine and norepinephrine levels of the infected poults showed a dose-dependent increase over levels in controls, with poults that were most heavily infected having the highest levels. The catecholamines appeared to show a classic stress-elicited response: this response increases with time to high levels during the acute stage of the infection, and then returns to levels approximately the same as those of the controls as the poults recover from the infection. Anorexia, or feed restriction, appeared to be primarily responsible for the increase in norepinephrine. However, epinephrine levels in the infected poults were significantly higher than in their pair-fed, uninfected counterparts, indicating that factors other than reduced feed consumption contributed to the increase. The data indicate that plasma catecholamines are increased during coccidial infection. As pressor compounds, they may contribute to the previously observed changes in blood pressure and heart function in infected poults. PMID- 1876560 TI - Simultaneous colonization of Campylobacter jejuni and Salmonella typhimurium in day-old chicks. AB - Day-old chicks were challenged with Campylobacter jejuni or Salmonella typhimurium or both to assess the influence of these two bacteria upon the colonization of one another. Median colonization dose (CD50), a measure indicating the number of organisms required to colonize one-half of the challenged chickens, was used to assess the influence of these organisms upon the colonization of one another. Chicks were gavaged with serial dilutions of 1) C. jejuni, 2) S. typhimurium, 3) dilutions of C. jejuni and a fixed level of S. typhimurium, or 4) dilutions of S. typhimurium and a fixed level of C. jejuni. Six days postchallenge, cecal contents were quantitatively assayed for the challenge organisms. Birds challenged with only C. jejuni or birds challenged with both C. jejuni and S. typhimurium had a CD50 of 120 C. jejuni cells. The CD50 values for S. typhimurium alone (48 cells) and S. typhimurium simultaneously colonized with C. jejuni (180 cells) were not significantly different (P less than .05). The colonization levels of either organism were generally correlated with the challenge dose and ranged up to 63 million cells per gram. It was concluded that the CD50 for both C. jejuni and S. typhimurium in 24-h-old chicks were similar, and the presence of one of these particular co-colonizers does not influence the CD50 of the other. PMID- 1876561 TI - Effect of surgical and chemical in ovo bursectomy on hatchability, mortality rate, and antibody response in hypertensive and hypotensive lines of turkeys. AB - The effect of in ovo bursectomy on hatchability, mortality rate, and antibody response to keyhole limpet hemocyanin (KLH) was studied in hypertensive and hypotensive lines of turkeys. Experiments were conducted to assess the optimal time to perform surgical in ovo bursectomy in turkey embryos for the lowest mortality rate. Factors such as the ease of operation, hatchability, and least deaths were considered. Surgical bursectomies at 25, 24, 23, and 22 day embryonation resulted in 75, 20, 0, and 10% hatchability, respectively. The surgical procedure performed at 25-day embryonation resulted in superior hatchability and ease of operation, and it was less traumatic as evidenced by fewer deaths. The hatchability of embryos injected with testosterone (TE) at 15 days incubation was 55%. Birds subjected to surgery or chemical treatment had increased mortality rates. Cyclophosphamide (CY) treatment at 1 and 2 days posthatch caused a significant increase in deaths over groups not treated with CY. Both primary and secondary KLH responses were significantly lower in bursectomized and TE-injected groups, than in shamoperated or nonoperated control groups. PMID- 1876562 TI - Use of ascorbic acid to prevent the decline in eggshell quality observed with saline drinking water. AB - Three experiments were carried out to determine the value of ascorbic acid in overcoming the poor eggshell quality problem associated with the use of saline drinking water. Laying hens were supplied with either town water or town water supplemented with NaCl, ascorbic acid, or a combination of NaCl and ascorbic acid. Supplementing the drinking water lf laying hens with NaCl (2 g/L) significantly increased the incidence of eggshell defects and significantly decreased eggshell quality. Simultaneous supplementation of the saline drinking water with ascorbic acid (1 g/L) prevented these detrimental effects. This response to ascorbic acid was dependent upon concentration. Ascorbic acid acted as a preventive rather than a remedial treatment: hens producing eggs with defective shells as a result of receiving saline drinking water failed to show any improvement in eggshell quality or any reduction in the incidence of eggshell defects when the saline water was supplemented with ascorbic acid. PMID- 1876563 TI - Diet dilution and compensatory growth in broilers. AB - Two experiments were conducted to note the response of broiler chickens to degrees of diet dilution from 4 to 11 days of age. In Experiment 1, broilers were fed conventional broiler diets from 0 to 4 and 11 to 56 days of age. From 4 to 11 days, birds were fed a conventional corn and soybean meal broiler starter, or the same diet in which major nutrients were replaced with 25, 40, or 55% ground rice hulls. Mineral and vitamin sources were not affected by dilution. Each of the three diluted diets together with an undiluted control diet was fed to three replicate floor pen groups of 30 male or 30 female broilers. In a second similar experiment, male birds were fed a regular broiler starter from 4 to 11 days or a diet diluted with 50% rice hulls. In this second experiment, rice hulls were substituted for all ingredients including those providing vitamin and mineral supplements. In Experiment 1, diet dilution resulted in a significant (P less than .05) reduction in body weight at 11 days of age, although by 42 days there was complete recovery of body weight with no change in overall efficiency of feed utilization. This same trend was seen in both sexes. Calculation of energy balance suggests these birds to have used energy very efficiently during the period of undernutrition. Diet dilution had no effect on carcass characteristics at 42 days, although for males at 56 days there was an indication of reduced abdominal fat content (P less than .05). In Experiment 2, compensatory gain was incomplete, although results were confounded due to an outbreak of infectious bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876564 TI - Ileal digestibility and urinary excretion of D-xylose and L-arabinose in ileostomized adult roosters. AB - An experiment with ileostomized adult roosters was conducted to determine the ileal digestibility and urinary excretion of D-xylose and L-arabinose. As a reference, D-glucose was included in the experiment. The sugars were tested at graded dietary levels of 2.5, 5.0, 7.5, and 10.0%. Mean ileal digestibility of D glucose and D-xylose was nearly 100%. Ileal digestibility of L-arabinose decreased linearly (P less than .05) with increasing dose level. The corresponding ileal digestibilities for L-arabinose at dietary levels of 2.5, 5.0, 7.5, and 10.0% were 95.5, 93.6, 80.3, and 74.6%. Both pentose sugars were partly excreted in the urine. The extent of this urinary excretion in percentage of intake increased linearly (P less than .05) as the dietary level increased. In roosters fed the 2.5% D-xylose diet, 7.2% of the D-xylose consumed appeared in the urine. This level increased to 20.2% when roosters were fed a diet containing 10.0% D-xylose. Corresponding values for L-arabinose at these dietary inclusion levels were 8.7 and 16.6%. PMID- 1876565 TI - Nutritional evaluation of soybeans varying in trypsin inhibitor content. AB - A series of experiments was conducted to assess, by various methods, the nutritional value of a raw, Kunitz inhibitor-free, low trypsin-inhibitor soybean variant (LTS) in comparison with raw conventional soybeans (RCS) and heated dehulled soybean meal (HDS). The gross energy, protein, and amino acid concentrations of LTS were similar to those of RCS. The protein quality of the soybeans was compared in two trials in which young chicks were fed 9% or 16% CP diets containing one of the soybeans as the sole source of dietary protein. The protein quality of LTS was superior to that of RCS but inferior to that of HDS. True digestibilities of amino acids and TMEn were determined with a precision-fed cockerel assay using conventional and cecectomized birds. No significant effect of bird type on digestibility was found. The mean digestibility of 16 amino acids in RCS, LTS, and HDS was found to be approximately 68, 83, and 92%, respectively. The TMEn of LTS was greater than that of RCS. Chick growth assays indicated that amino acid bioavailability values of lysine and TSAA for LTS were greater than those for RCS but slightly lower than those for HDS. In an additional chick assay with a corn and HDS diet (22% CP), the dietary HDS protein was replaced with LTS or RCS protein at 25, 50, 75, or 100%. Performance of chicks fed LTS was better than that of chicks fed RCS at all replacement levels, but the difference was not significant at the 25% replacement level. Feed efficiencies of chicks fed 25 or 50% of the dietary soybean protein as LTS were not significantly different from that of chicks fed the corn and HDS control diet. The results of the present study indicated that the nutritive value of LTS is substantially greater than that of RCS but somewhat lower than that of HDS. PMID- 1876566 TI - Effect of rearing regimens on pullet growth and subsequent laying performance. AB - Treatments consisted of eight pullet dietary regimens: high protein with low, medium, or high ME; low protein with high ME, step-up protein, and diets with gradually decreasing protein levels and increasing ME levels with deficient methionine and TSAA levels, recommended methionine levels (TSAA-deficient), or recommended methionine and TSAA levels. Two additional regimens were introduced at 20 wk by selecting light and heavy birds, from caged birds maintained under high protein, medium ME conditions. Laying performance was measured from 20 to 64 wk. During the rearing period, birds fed the low energy and the methionine deficient regimens consumed less energy (P less than .05). Body weight at 8 wk was affected by initial protein levels (P less than .05), but such effect was not seen after 16 wk of age. Birds on the step-up protein regimen consumed less feed during the laying period but also produced less egg mass (P less than .05). Birds with heavier body weights at 20 wk had better laying performance than birds with lighter body weights (P less than .05). A rearing regimen (0 to 20 wk) that resulted in a total protein intake of 1,140 g and a total ME intake of 20.0 Mcal was shown to control final pullet body weight and maximize laying performance; although at higher ME intake (21.5 Mcal) no detrimental effect was seen. PMID- 1876567 TI - Effect of diet and population density on male turkeys under various environmental conditions. 1. Turkey growth and health performance. AB - The performance of 1,312 male market turkeys (Large White, Nicholas strain) from 0 to 20 wk of age fed diets varying in feed form and energy level was measured under two stocking densities (.21 or .46 m2 per bird) and four lighting and temperature programs. The four diets were 1) corn and soybean meal with 1% supplemental fat, mash (CSM); 2) as 1, pelleted (CSP); 3) as Diet 1 but with 1, 2, 4, 6, and 8% supplemental fat during 0 to 4, 4 to 8, 8 to 12, 12 to 16, and 16 to 20 wk of age, respectively (CSF); and 4) as Diet 1 but with barely included at 0, 20, 35, 50, and 65% during the respective 4-wk age periods (CSB). The four light and temperature programs were 1) Environment A with intermittent light [4 [2 h light (L):4 h dark (D)]] in combination with cycling temperature at 7 and 21 C during light and dark photoperiod, respectively; Environment B with intermittent light, 21 C; Environment C with continuous light (18L:6D) and cycling temperature of 7 to 21 C; and Environment D with intermittent light, 7 C. Lighting and temperature programs started at 1 and 4 wk of age, respectively. Body weights at 20 wk of age decreased (P less than .05) with increasing temperature (13.86 versus 12.26 kg for Environments D and B, respectively) with cycling temperature intermediate (13.51 kg for Environment A). Intermittent light (P less than .05) improved BW and feed conversion by 3.4 and 2.0%, respectively, compared with continuous light. Rearing males at .21 m2 per bird versus .46 m2 per bird decreased weight (P less than .05) by 5.5%. Twenty-week BW of males fed the CSP (13.52 kg) and CSF (13.58 kg) diets were greater (P less than .05) than those fed CSM (12.90 kg) and CSB (12.69 kg) diets. Significant (P less than .05) interactions between diet, environment, and density were not detected for most performance characteristics. Environmental measurements indicated higher dust and ammonia levels in the warm environment (B). Isolates of aspergillus and incidence of airsacculitis at time of processing were greatest in Environment B. PMID- 1876568 TI - Effect of diet and population density on male turkeys under various environmental conditions. 2. Body composition and meat yield. AB - Large White Nicholas male turkeys were reared at two stocking densities (.21 or .46 m2 per bird) and fed one of four diets: 1) control corn and soybean (mash) with 1% fat (CSM); 2) as Diet 1, pelleted (CSP); 3) as Diet 1 with supplemental fat increasing from 1 through 8% with age (CSF); and 4) as Diet 1 with barley at 0, 20, 35, 50, and 65% during successive 4-wk periods (CSB). The turkeys were reared in four environments: (A) intermittent light schedule [4(2 h light (L):4 h dark D))] with temperature at 7 or 21 C during light and dark photoperiod, respectively; (B) and (D) with intermittent light (2L:4D) with a constant 21 and 7 C temperatures, respectively; (C) continuous light cycle (18L:6D) with temperatures as in Environment A. At 20 wk of age, two turkeys per replicate pen, were killed for determination of body composition and meat yield. Compared with turkeys fed CSM diet, those on CSF and CSP diet had increased percentage carcass fat. Meat yield per bird and percentage carcass fat were greater for turkeys reared at .46 m2 per bird compared with rearing at .21 m2 per bird. Pelleting and fat supplementation resulted in significantly increased amounts of breast meat and leg compared with CSM. Breast meat yield (percentage) and amount were greater at 7 C (Environment D) than at 21 C (Environment B) and the cycling regimen (Environment A). Percentage abdominal fat was greatest at 7 C. Interactions of environment and diet were detected for breast meat yield percentage (P less than .023) and weight (P less than .036). Diet type had no effect on percentage breast meat or weight in Environment C. An increased amount of breast meat was obtained by feeding CSP in Environments A, B, and D, and dietary fat supplementation increased breast meat yield in Environments A and D over CSM treatment. PMID- 1876569 TI - Effects of dietary amino acid levels on bone development in broiler chickens. AB - Studies with several species suggest that dietary protein may influence bone calcification. Six pens of six male broilers in two consecutive trials were fed from 1 to 21 days either .5 or 1.0% Ca in diets with 80, 90, 100, 110, or 120% of the amino acid (AA) standards suggested by Thomas et al. in 1986 at a constant .46% nonphytate P. The BW and feed conversion rate (FCR) were determined, and bone measurements were taken. Both AA and Ca levels influenced BW with an interaction of the two factors. The Ca level, but not AA level, influenced FCR. The lower Ca level inhibited feed intake. Increasing AA levels reduced bone ash but did not affect tibia breaking strength. There was an interaction of AA and Ca on tibia ash, tibia weight, and tibia length. The higher AA levels supported normal linear growth of the tibia but decreased rate of calcification, especially in the diets with .5% Ca. In diets with marginal Ca levels, higher AA levels may reduce bone calcification. PMID- 1876570 TI - Immune response of chicks fed various levels of zinc. AB - Five experiments were conducted to determine the effects of zinc intake on the immune response of chicks. Ancona chicks (Experiment 1), New Hampshire (Experiment 2), New Hampshire x Leghorn (Experiment 3), and broiler chicks (Experiments 4 and 5) were fed semipurified (Experiments 1, 2, 3, and 4) or corn and soybean meal diets (Experiment 5) containing from 8 to 88 micrograms zinc/g of diet. An extra group of chicks in Experiments 1, 2, and 4 were fed a diet adequate in zinc but at an intake similar to that of chicks fed the lowest zinc level in each respective experiment. Low zinc intake (less that 28 micrograms zinc/g of diet) suppressed body weight at all times measured. The effect of zinc intake on the size of lymphoid tissues was variable, but at 5 wk of age, chicks fed 8 micrograms zinc/g of diet had smaller bursae of Fabricius and thymi than those fed additional zinc. Zinc intake had no influence on the primary and secondary immune response to SRBC or delayed hypersensitivity to phytohemagglutinin-P (PHA) or human gamma globulin in Ancona and broiler chicks. However, zinc intake did have a small effect in chicks from the New Hampshire parents. In Experiments 1, 2, and 4 (at least at certain times), antibody titers were reduced in pair-fed chicks. Thus, although zinc supplementation at the levels of practical diets did not affect immune function, feed restriction did. PMID- 1876571 TI - The influence of various calcium and phosphorus levels on tibia strength and eggshell quality of pullets during peak production. AB - One thousand and eighty DeKalb XL pullets were randomly allocated to nine treatments and arranged in a 3 x 3 factorial to determine the effects of three levels of dietary calcium (2.75, 3.75, and 4.25%) and three levels of dietary available phosphorus (.30, .40, and .50%) on eggshell quality and tibia weight, tibia breaking strength, tibia ash, and bone mineral content of pullets during peak production. Feed consumption increased as dietary calcium or phosphorus increased. Increasing dietary calcium caused a significant linear increase in egg specific gravity, but dietary phosphorus had no significant effect on egg specific gravity. Calcium and phosphorus levels did not significantly affect egg production, body weight, plasma chloride, or phosphorus. Ionized calcium increased significantly as dietary calcium increased. Tibia breaking strength, tibia weight, tibia ash, and bone mineral content increased significantly with increasing dietary calcium. Dietary phosphorus had no significant effect on these parameters. However, when 2.75% calcium was fed, reducing dietary phosphorus significantly decreased tibia weight, tibia ash, and bone mineral content. PMID- 1876572 TI - The effect of clenbuterol supplementation on growth performance and on plasma hormone and metabolite levels of broilers. AB - In the present experiment, clenbuterol was supplemented (.42 ppm) from Day 1 or from 2 or 4 wk of age until slaughter age (6 wk). The effects on growth performance and on plasma hormone and metabolite profiles were investigated at 2, 4, and 6 wk of age in male and female broilers. There were no consistent or cumulative effects of clenbuterol feeding on growth and feed efficiency. Clenbuterol feeding from Day 1, but not later, depressed subsequent feed intake. Relative abdominal fat pad weight was reduced profoundly and was even more pronounced after prolonged supplementation and for females. Fat content of thigh meat (including skin), but not of breast meat (without skin), was reduced by clenbuterol feeding. No consistent effects of clenbuterol supplementation on plasma thyroid hormones, growth hormone, insulin-like growth factor-I, and corticosterone levels were detected. Very low density lipoprotein (VLDL) concentrations were depressed in male broilers fed clenbuterol for 6 wk, but the plasma triglyceride level did not follow this pattern. There was no evidence for a consistent effect of clenbuterol on lipolysis in vivo, measured by plasma glycerol level. Between 4 and 6 wk of age, plasma VLDL and glycerol levels decreased in females but increased in males. This corresponds to the higher fat deposition in females. However, the most consistent effects were age-related changes in the plasma levels of most hormones and metabolites. From the present study, it seems that clenbuterol acts primarily on fat deposition, the extent being dependent on sex, location of fat, and duration of beta-adrenergic agonist supplementation. PMID- 1876573 TI - Pharmacokinetics of ursodeoxycholic acid in rat. AB - The pharmacokinetic behaviour and metabolism of ursodeoxycholic acid (UDCA) have been studied in the rat. After oral administration of both 3H-labelled (4 muCi/kg body wt) and unlabelled (20 mg) UDCA, UDCA appeared in serum almost entirely in conjugated form (taurine conjugated); UDCA was present in bile mostly as taurine conjugated; the more relevant metabolite is 3 alpha,6 alpha, 7 beta trihydroxycholanoic acid which represents 10% of the total bile acid pool. UDCA increased bile flow and selectively decreased biliary cholesterol secretion, while phospholipid secretion was unaffected. Faecal UDCA excretion was 15-20% while the urinary extraction was 1.5% during 24 h. The data show that UDCA, when administered in high dose, is promptly secreted into bile almost entirely metabolized to tauroursodeoxycholic acid, where it (1) desaturates the cholesterol in bile, (2) exerts choleretic properties. PMID- 1876574 TI - Blood content in guinea-pig tissues: correction for the study of drug tissue distribution. AB - The blood content in different organs or tissues of guinea-pigs was determined by means of [125I]bovine serum albumin. The blood distribution expressed as percentage of total body blood for various organs or tissues ranged from 0.35 (adipose) to 17.5 (muscle)%. The blood content in tissue preparations expressed as the blood background correction factor, F (ml blood/g wet tissue) depended on the extent of bleeding during experiment; that factor can cause a considerable difference in the results of a tissue distribution study of a drug. Blood content was high in the lung (0.36 ml/g), heart, liver, kidney and spleen, but low in adipose and brain tissues (0.021 ml/g). The distribution of valproic acid in various tissues of guinea-pigs after intravenous injection was determined from the homogenates of isolated organs. The results showed that blood contamination can greatly alter the data of tissue distribution of a drug to as much as 25%. This study proposed a maximum (non-bled) and a minimum (extreme-bled) blood background correction factor for respective tissues of guinea-pigs, as well as equations for correcting the blood contamination in tissue during the drug distribution study. The results suggest that to obtain an exact analysis of drug concentrations in specific tissues, a correction for the blood of that specific tissue is necessary. PMID- 1876575 TI - Continuous read-out of cytochrome b, flavin and pyridine nucleotide oxido reduction processes in the perfused frog heart and contracting skeletal muscle. AB - The time-sharing instrument for continuous read-out of the fluorescence levels of NAD(P)H and oxidized-flavoproteins, which also makes simultaneous dual beam differential absorption measurements of cytochrome b, has been applied to the study of the metabolic control of the frog heart, perfused in vitro with normal and variously modified Ringer solutions, and to the frog skeletal muscle in situ. In the ionically depolarized resting heart, the long term kinetic analysis of the redox processes during oxygen/anoxia transitions has proved to be an adequate method for identifying and following three fundamental intracellular redox compartments: (1) the respiratory system, (2) the microsomal system, and (3) the glycolytic system. The provision of substrates and/or suitable inhibitors has allowed the description of functional interrelationships within the mitochondrial and the cytoplasmic spaces. The ouabain major site of response has been located on the cytosolic pyridine nucleotides, with a very small response in the mitochondrial space. The switching on and off of substantial fractions of the NAD(P)+/NAD(P)H and Fpoxidized/Fpreduced pools has been observed, which helps to clarify the large phase shift between the overall pyridine nucleotide and flavin oxidation-reduction processes, during the cycle of the spontaneously beating heart and during skeletal muscle contraction and recovery, here originally prompted out. PMID- 1876576 TI - Mechanism of dichlorovos-induced inhibition of calcium-dependent contractions in the rat tail artery. AB - The inhibitory effect of dichlorovos (an organophosphate pesticide) on Ca(2+) dependent contractions has been studied in isolated helical strips of rat tail arteries. Isometric contractions were evaluated under standard organ bath conditions. Dichlorovos caused concentration-dependent relaxation of 10(-7) M NE induced contractions as well as inhibition of both phasic and tonic components of NE contractions. Extracellular calcium-dependent contractions in K(+)-depolarized medium as well as NE-induced contractions due to mobilization of membrane-bound calcium pool and intracellular calcium-dependent caffeine contractions were significantly attenuated by dichlorovos. The results strongly support our previous observation that dichlorovos interferes with calcium metabolism in the rat tail artery. PMID- 1876577 TI - The effects of electrical stimulation, adenosine and adenosine-5'-triphosphate (ATP) on mouse rectal muscle. AB - The effects of electrical field stimulation and of purine compounds, adenosine and adenosine-5'-triphosphate (ATP) were examined on the mouse isolated rectum. Electrical field stimulation induced frequency-dependent contractions of mouse rectal muscles which were potentiated by physostigmine and inhibited by atropine or tetrodotoxin. Contractile amplitude at 37 degrees C was significantly (P less than 0.05) greater than at 25 degrees C, but the degree of potentiation by physostigmine was significantly (P less than 0.05) greater at 25 degrees C. ATP (1.6 x 10(-4)-1.28 x 10(-3) M) and adenosine (1.8 x 10(-4)-1.48 x 10(-3) M) inhibited in concentration-related fashion contractile responses induced by KCl (1.34 x 10(-2) M-1.07 x 10(-1) M) by acetylcholine (2.2 x 10(-7) M-1.4 x 10(-5) M) and by CaCl2 in high KCl (120 mM)-CaCl2-free Tyrode solution. Theophylline and quinidine ('purinoceptor' antagonists) antagonized ACH contractile effects and so could not be satisfactorily employed in the characterization of the purine receptors in the mouse rectum. It may be concluded from this study that in the mouse rectum, acetylcholine is an excitatory neurotransmitter and that there is a non-adrenergic, non-cholinergic inhibitory neuromuscular transmission in this tissue. Further, ATP and adenosine have been demonstrated to cause relaxation in this tissue by possibly a post-synaptic mechanism involving inhibition of Ca2+ influx into the depolarized muscle. PMID- 1876578 TI - [Immune deficiency and its sequelae. On the 75th Congress of the German Society of Pathology in Friedrichshaven 21-15 May 1991]. PMID- 1876579 TI - [Quality assurance in pathology]. PMID- 1876581 TI - [Forensic medicine topics in pathology. I. On the legal status of clinical autopsy]. PMID- 1876580 TI - [Medical waste in pathology. Recycling, disposal--cost control]. PMID- 1876582 TI - [Uncertain malignant peritoneal tumors in 28 years of autopsy. Histologic reclassification]. PMID- 1876583 TI - [Lectin histochemical study of HIV-associated changes in the central nervous system with mistletoe lectin I (ML I)]. PMID- 1876584 TI - [Osteoglophonic skeletal dysplasia--a variant of generalized fibrous dysplasia? Case report and review of the literature]. PMID- 1876585 TI - [Curt Froboese is 100 years old]. PMID- 1876586 TI - [Disorders of the innervation of the large intestine--classification and diagnosis. Results of a consensus conference of the Society of Gastroenteropathology 1 December 1990 in Frankfurt/Main]. PMID- 1876587 TI - [Malignant diseases of the respiratory tract]. PMID- 1876588 TI - [Etiology of bronchial cancer: smoking, passive smoking, environment and occupation]. AB - The inhaled tobacco smoke is the most important determinant in the etiology of lung cancer and there is a clear dose-effect relation between lung cancer risk and the duration of smoking, the number of cigarettes and the intensity of inhalation. The opinions about lung cancer risk from passive smoking are divided and the published data are still in discussion. Occupational substances include chromates, nickel, beryllium, alkylated compounds, vinylchloride, arsenic compounds and in particular asbestos. Fortunately air pollution has no or small part in the etiology of lung cancer. PMID- 1876589 TI - [Tumor markers, significance for clinical diagnosis]. AB - A wide variety of tumour markers has been described in bronchial carcinoma. Clinical studies have been most frequently conducted with the substances CEA, NSE, CK-BB and for the peptid hormones ACTH, calcitonin and ADH. The serum levels for CEA, NSE and CK-BB correlate to a certain extent with the stage of the tumour disease, the prognosis and the survival time. On the other hand, the peptid hormones have no clinical significance on account of their low sensitivity and specificity. Outside of clinical studies the determination of tumour markers in bronchial carcinoma is clinically irrelevant. PMID- 1876590 TI - [Immunohistochemical markers in lung tumors--a status evaluation]. AB - Immunohistochemical investigations on tumours of the lung and pleura led to an enlarged knowledge about the characterization of the tumours biology and the typical morphological feature of lung tumours. A helpful tool was the elaboration of monoclonal antibodies against different cellular proteins and proliferation markers which revealed a detailed information on proliferation tendency and immunological reaction of the tumour. The most informative parameter in adenocarcinomas was the distinguished expression of the carcino embryonic antigen (CEA). The immunohistochemical investigations are helpful for the differentiation of primary and secondary lung- and pleural tumours, but also pointed out a high heterogeneity of malignant lung tumours. Nevertheless the present tumour markers- be considered to give an indication for diagnosis, therapy and prognosis of the development of the disease--have to be correlated with clinical and biochemical data for further estimation of their value. PMID- 1876591 TI - [Early and late postoperative complications in thoracic surgery interventions]. AB - Two types of postoperative complications should be distinguished, i.e. early complications including a lethality within 30 days and delayed complications which may occur after several years. In the period between 8/1985 and 12/1987 216 operations were carried out on patients with bronchial carcinoma. The operative lethality rate was 2.3%. The most frequently performed operation was lobectomy with 59% followed by pneumonectomy including extended pneumonectomy with 17.5%. 57.7% of patients with bronchial carcinomata were resected in the early stage I and II, and 26.4% of patients in stage IIIa. Squamous cell carcinomata occurred most frequently, with an incidence of 41%. Of the common postoperative complications cardiac arrhythmia was to be found most often (27%). Pulmonary embolism developed in 5% of all cases, cerebral complications in 3.7%, wound infections in 2.3% and post-operative haemorrhages in 1.3%. Bronchus stump insufficiency and dehiscence of suture were found in 2.2%, and pleural empyema in 4.2% of the complications directly resulting from the operation. Only 6 of 9 patients had suffered an persistent bronchopleural fistula lasting 7 days. Infections of the respiratory tree were identified in 18.3% and pneumonia in only 8.3% of cases. Delayed empyemas and bronchus fistulas belong in the category of delayed complications. The risk of deformation of the vertebral column caused by processes of involution in the cavity of pneumonectomy should be kept in mind following pneumonectomy. A distinction shall be made between the postthoracotomy syndrome an classical intercostal neuralgia, which has a sharply defined clinical picture and may be treated by operative neurolysis or resection of the nerve. PMID- 1876592 TI - [Pleural mesothelioma: etiology and practical consequences]. AB - In the course of the past few decades there has been a heavy world-wide increase in the incidence of mesotheliomas among the industrialised nations. A characteristic feature of this is an extremely great difference in respect of the expected incidence of the tumour between persons who had been in contact--even though a long time back--with asbestos fibre dust, or who worked or resided near sources of asbestos emission, or who had contact with asbestos fibres in their household, on the one hand, and with the rest of the population on the other. Hence, pleuromesothelioma is not only a tumour signalling the risk brought about by the presence of asbestos or of zeolites in the environment, it is also so to say the environmental tumour par excellence. Among the members of those artisan professions where products containing asbestos are being employed, pleuromesotheliomas have been a far more frequent source of professionally conditioned cancer than among the workers of the asbestos industry proper. Since the latency period is as a rule 30 years, the physician must go back scrupulously 20 to 60 years in the patient's previous history to find out whether there had been an exposure to asbestos at any time that would induce tumour formation, the more so since a mere couple of weeks' exposure can be enough to induce a tumour so many years later. On account of the pleurotropy of inhaled asbestos fibres, pointers to an asbestosis of the lungs and/or pleura should be followed up on target. Further practical consequences are discussed. PMID- 1876593 TI - [Diagnosis of diffuse pleural mesotheliomas]. AB - Main clinical symptoms and signs in diffuse malignant pleura mesotheliomas are thoracic pain (58%) and gradually increasing dyspnoea (50%). Pleural effusion is the most frequent x-ray manifestation (80%), but it is haemorrhagic in only 50% of the cases. Cytology has a sensitivity of approx. 50%; with the epithelial type it yields definitely better results (76%) than with the biphasic (49%) or fibrous (25%) types. The carcinoembryonic antigen level is usually low in the effusion, but enhanced values do not exclude a diffuse malignant pleura mesothelioma. For differentiation against metastasised adenocarcinomas, which is often difficult, it is recommended to effect histological examination of the tumour tissue obtained either by pleura punch biopsy (sensitivity 40-50%) or by thoracoscopy (sensitivity 90-95%). In this manner, accurate staging is possible in conjunction with CT. Particularly in case of fibrous growth, it is sometimes only thoracotomy that enables final diagnostic clarification. PMID- 1876594 TI - [Therapy of malignant pleural mesothelioma]. AB - The different therapeutical procedures of malignant pleura-mesothelioma are reviewed. A comparison of studies published so far is difficult or impossible because of the heterogeneity of the clientele and of the protocols. The median survival of untreated patients is 6 months from the date of diagnosis. Radical surgical treatment results in 2-year survival in 10-37%. As these data are not different from those of untreated patients, and additionally this procedure is associated with a perioperative mortality of 6-31%, the indication for radical resection has to be applied very critically. As pleuramesotheliomas are often resistant to radiotherapy, tumour remissions under this treatment are extremely rare. However, this therapy has a palliative analgesic benefit. Chemotherapy with anthracycline containing combinations leads to partial remissions in 20% and a median survival of 11 months. Whether multimodal therapeutical concepts are advantageous or not, will have to be established. PMID- 1876595 TI - Ultrastructural characterization of calcitonin gene-related peptide-containing fibers and islet cells in the rat pancreas. AB - Morphology and structural organization of calcitonin gene-related peptide (CGRP) immunoreactive nerve fibers and islet cells in rat pancreas were analyzed with light and electron microscopic immunocytochemistry. Immunoreactive axons innervate exocrine and endocrine parenchyma, but are most abundant in connective tissue septae between pancreatic lobules and within the perivascular space of small arterioles. In the stromal compartment and perivascular space, immunoreactive product is confined to thin, unmyelinated axons, which represent a prominent component of large nerve bundles, composed of numerous, other, unlabeled axons and dendrites. Immunoreactive axons and terminals display multiple varicosities, filled with lucent spherical vesicles (40 nm average diameter), and are often in direct contact with unlabeled dendrites, presumed to arise from intrinsic pancreatic neurons. However, definitive synaptic contacts involving immunoreactive axon terminals were never observed, nor was CGRP immunoreactivity ever detected in neuronal cell bodies within intrapancreatic ganglia. Cellular immunoreactivity is relegated to perikarya at the peripheral margin of each islet of Langerhans, which emit one or more short, thick processes, which often terminate upon fenestrated capillaries. Immunoreaction product in these cells is concentrated in large secretory vesicles (approximately 230 nm diameter), which are dispersed throughout the somata and frequently appear to open into the perivascular space of capillaries. Immunoreactive axons, innervating the islets, are sparse and do not appear to have preferential association with immunoreactive cells. Present findings provide further evidence for a dual role of CGRP in pancreatic functions via a neuronal pathway and hormonal mechanisms. PMID- 1876596 TI - Pancreatic secretion by the anaesthetized rabbit in response to secretin, cholecystokinin, and carbachol. AB - Considerable differences exist among species in the patterns of regulation of pancreatic secretion. Although rabbit pancreas is quite often used for in vivo and in vitro studies of pancreatic function, responses of this gland in vivo to common pancreatic stimuli have never been characterised in detail. That was the purpose of this study. The data demonstrate the existence of a spontaneous fluid secretion that can be increased by intravenous infusions of secretion (sevenfold), cholecystokinin-octapeptide (CCK8) (threefold), and carbachol (sixfold). The electrolyte composition of the secretion evoked by each of these stimuli was similar: sodium and potassium concentrations were constant and slightly higher than those in plasma at all secretory rates, whereas bicarbonate concentration rose with secretory rate to approach a plateau of about 125 mmol/L, and chloride concentration fell to a plateau of about 35 mmol/L. In terms of protein secretion, secretin caused a small but significant rise in output, while CCK8 and carbachol evoked the expected large increase. Thus, regulation of pancreatic electrolyte secretion in rabbit differs from that in dog, cat, and human, on the one hand, and rat, on the other hand, and most closely resembles the pattern observed in guinea pig. PMID- 1876597 TI - The effect of dopamine in a model of biliary acute hemorrhagic pancreatitis. AB - Perfusion of the main pancreatic duct in cats with a dilute solution of bile salts increases ductal permeability. Subsequent perfusion of a permeable duct with activated pancreatic enzymes results in acute edematous pancreatitis. Simultaneous infusion of 16-16 dimethyl-PgE2 converts edematous pancreatitis to acute hemorrhagic pancreatitis (AHP). AHP may be associated with a reduction in pancreatic blood flow; it is certainly associated with increases in microvascular permeability. Low dose dopamine is a splanchnic vasodilator and may also reduce pancreatic microvascular permeability through beta agonist effects. In these studies, we investigated the effect of dopamine in an established feline model of biliary AHP. We also studied its effect on blood flow in both normal pancreas and after induction of AHP. We found that dopamine significantly reduced the degree of pancreatic inflammation, even when administered up to 12 h after onset of biliary AHP. However, the drug had no significant effect on blood flow either in normal pancreas or in the gland affected by hemorrhagic pancreatitis. We concluded that the effect of dopamine was most likely due to its ability to reduce pancreatic microvascular permeability. PMID- 1876598 TI - Pancreatic polypeptide and peptide YY inhibit the denervated canine pancreas. AB - Pancreatic polypeptide and peptide YY are inhibitors of pancreatic exocrine secretion in vivo but not in vitro, which suggests secondarily mediated mechanism(s) of action. To determine the role of extrinsic neural and intrinsic cholinergic elements on this inhibitory effect, a total of nine dogs underwent two-stage extrapancreatic denervation and creation of a chronic pancreatic fistula. After recovery, pancreatic polypeptide or peptide YY (400 pmol/kg/h) was administered during the intermediate hour of a 3-hour secretion (125 ng/kg/h)/cholecystokinin (50 ng/kg/h) infusion. Exocrine secretion pancreatic polypeptide or peptide YY hours was compared with that of the first and third hours. The studies were then repeated during infusion of atropine (10 micrograms/kg/h). Despite extrinsic denervation, pancreatic polypeptide and peptide YY significantly inhibited secretin/cholecystokinin-induced pancreatic output. Although less profound, significant inhibition persisted in the presence of an atropine background. Pancreatic polypeptide or peptide YY infusion also decreased the exocrine response to meal stimulation. We conclude that the inhibitory effects of pancreatic polypeptide and peptide YY are not mediated by extrapancreatic, and possibly not by intrapancreatic cholinergic, neural pathways. PMID- 1876599 TI - Intracolonic infusion of bile salt stimulates release of peptide YY and inhibits cholecystokinin-stimulated pancreatic exocrine secretion in conscious dogs. AB - The purpose of this study was to examine the effect of transanal (intracolonic) infusion of bile acid on release of peptide YY (PYY) and cholecystokinin (CCK) stimulated pancreatic exocrine secretion in seven conscious dogs. CCK-8 (50 ng/kg/h) was given intravenously for 120 min and either taurocholic acid (TA, 1 or 2 mmol/h) or saline was infused transanally (150 ml/h) during the 0-60-min period of CCK infusion. Transanal infusion of TA (1 or 2 mmol/h) significantly inhibited output of CCK-8-stimulated pancreatic protein, compared to transanal infusion of saline during the first 60 min. On the average, the magnitude of inhibition was approximately 45%. Plasma concentrations of PYY increased significantly in response to intracolonic infusion of TA or saline. Transanal infusion of TA (1 or 2 mmol/h) significantly increased plasma levels of PYY when compared with transanal infusion of saline during the first 60 min. The magnitude of the increase of plasma PYY levels was approximately 50 pg/ml (p less than 0.05). Plasma levels of pancreatic polypeptide were not altered significantly by transanal infusion of TA. Our results suggest that release of endogenous PYY by TA in the colon plays a role in the inhibition of CCK-stimulated pancreatic exocrine secretion. Bile salts in the hindgut may participate in the physiologic regulation of pancreatic exocrine secretion by stimulation of release of ilealcolonic PYY. PMID- 1876600 TI - Effect of a new synthetic protease inhibitor on beta-endorphin release during acute pancreatitis in dogs. AB - The effect on endogenous beta-endorphins of a new synthetic protease inhibitor was studied in acute pancreatitis. Pancreatitis was induced by the injection of autologous bile mixed with trypsin into the main pancreatic duct after ligation of the accessory duct. Plasma beta-endorphin concentrations and cardiovascular function were measured. Ten dogs (control group) were given 10 ml/kg/h of lactate Ringer's solution intravenously beginning 1 h before the induction of pancreatitis and continuing throughout the experiments. Six dogs received an intravenous infusion of 3 mg/kg/h of a new synthetic protease inhibitor, E-3123 (4-(2-succinimidoethylthio)4-geranidinobenzoate methanesuLfonate), in lactate Ringer's solution soon after the induction of pancreatitis. Plasma beta-endorphin concentrations in the control group increased significantly. However, plasma beta endorphin levels in the protease inhibitor group did not increase as in the control group. The protease inhibitor infusion improved hypotension, myocardial depression, and plasma lactate, suggesting that the inhibitory effect of the protease inhibitor on beta-endorphin release contributed to the improvement. PMID- 1876601 TI - Inhibitory action of islet amyloid polypeptide and calcitonin gene-related peptide on release of insulin from the isolated perfused rat pancreas. AB - Islet (or insulinoma) amyloid polypeptide (IAPP) is a 37-residue peptide recently purified from amyloid deposits in the pancreas of patients with type 2 diabetes and from amyloid deposits of a human insulinoma. IAPP immunoreactivity has been identified in islet B cells of diabetic and nondiabetic humans. IAPP is structurally similar to calcitonin gene-related peptide (CGRP). The purpose of this study was to examine the effects of IAPP and CGRP on glucose- and carbachol stimulated release of insulin and pancreatic polypeptide (PP) from the isolated perfused rat pancreas. IAPP and CGRP, at 10(-7) M, failed to inhibit glucose stimulated (16.7 mM) release of insulin. At the same concentration, however, IAPP significantly (p less than 0.05) inhibited carbachol-stimulated (10(-7) M) release of insulin by 30%, and CGRP significantly inhibited carbachol-stimulated release of insulin by 33% when compared with the control group. IAPP also significantly decreased carbachol-stimulated release release of PP. IAPP and CGRP, at 10(-8) M, did not inhibit carbachol-stimulated release of insulin and PP. These results suggest that IAPP and CGRP may have roles in the regulation of secretion of insulin. IAPP may inhibit secretion of insulin, at least in part, by blocking cholinergic mechanisms. PMID- 1876602 TI - Tolbutamide stimulates proliferation of pancreatic beta cells in culture. AB - To investigate the beta-cell cytotrophic action of tolbutamide, pancreatic cells were dissociated from neonatal rat pancreata and then cultured for 10 days in the presence of various concentrations of tolbutamide. After counting insulin positive beta cells, dose-response curves were plotted and analyzed. Increasing concentrations of tolbutamide cause an increase in beta-cell numbers until a maximum response is reached at a concentration of about 100 micrograms/ml. At greater concentrations, tolbutamide becomes inhibitory. At concentrations of 100 micrograms/ml of tolbutamide, beta-cell numbers are doubled. We further investigated the effect of glucose on tolbutamide-induced stimulation. Tolbutamide fails to stimulate beta cells after culture in medium containing low glucose concentrations. High concentrations of glucose are required for tolbutamide action. Preexposure for as little as 16 h to low glucose abolishes the stimulatory action of tolbutamide. The experiments indicate that adequate glucose concentrations are necessary for the preservation of tolbutamide-induced beta-cell survival and proliferation. Addition to the culture medium of the calcium channel blocker diltiazem or the calmodulin antagonist chlorpromazine affects a decrease in beta-cell numbers. This decrease depends on the concentration of the drug. Addition of tolbutamide reverses that decrease, which suggests that calcium is required for beta-cell survival and proliferation. Tolbutamide action seems to be specific, since fibroblasts are unaffected at concentrations of tolbutamide that are stimulatory for beta cells. At high concentrations, tolbutamide is cytotoxic for fibroblasts. Comparison with other sulfonylureas supports the superior activity of tolbutamide. The "second generation" sulfonylurea glyburide is cytotoxic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876603 TI - Definitions and classifications of pancreatitis. AB - The historical progress of medical knowledge has followed two primary courses. One course has been based mostly on pathology: the description of specific groups of features and of the corresponding causes and symptoms, i.e., the description of different diseases that are progressively distinguished one from another. At the present time, disorders of molecular biology as well as pathological lesions are increasingly playing a role in the definition of diseases. The second course is a preliminary step to the first: when pathological data have not been available, patients have been classified according to symptoms. This does not lead to the description of the diseases but rather of the syndromes. It is puzzling to see that this obsolete method is still commonly used in pancreatology. PMID- 1876604 TI - Pancreaticoduodenal transplantation with enteric drainage following native total pancreatectomy for chronic pancreatitis: a case report. AB - Pancreas transplantation is usually performed in patients with denovo type I diabetes, who have advanced secondary complications. We report a case in which whole pancreaticoduodenal transplantation, with enteric drainage, was performed to correct both endocrine and exocrine deficiencies in a patient with hyperlabile diabetes and steatorrhea, unresponsive to oral enzyme replacement therapy, following staged total pancreatectomy for idiopathic or familial chronic pancreatitis. The transplant was performed one year after completion of native pancreatectomy and immediately established an insulin-independent euglycemic state, with normal oral and intravenous glucose tolerance test results and correction of steatorrhea. Beginning one year posttransplant, the patient had intermittent episodes of steatorrhea, associated with mild elevation of blood sugar levels, which were presumed to be due to rejection and, indeed, responded to antirejection treatment with antilymphocyte globulin and temporary increases in steroids dosages. At 20 months posttransplant, steatorrhea did not respond to antirejection treatment and an acute abdomen developed. Laparotomy revealed a perforated graft duodenum, which was resected; pathology showed transmural necrosis secondary to chronic rejection. The pancreas graft itself was left in situ, disconnected from the intestinal tract. The patient remained normoglycemic after graft duodenectomy but resumed oral enzyme replacement therapy in an attempt to combat recurrence of severe steatorrhea. However, his overall situation remained improved compared to pretransplant, since the exocrine deficiency was tolerable in the absence of a diabetic state. Ten months postgraft duodenectomy (38 months posttransplant), elevations in blood sugar levels were treated with another course of antirejection treatment and levels temporarily declined. At 14 months postgraft duodenectomy (42 months posttransplant), graft endocrine function again declined and exogenous insulin was resumed. Six months later, four years after the original transplant, a new enteric-drained pancreaticoduodenal graft was placed, once again resulting in an insulin independent, steatorrheafree state. With improvements in immunosuppression, pancreas transplantation could be offered to selected patients with hyperlabile diabetes, following total pancreatectomy for benign disease; if the enteric drainage technique is used, in the absence of rejection, exocrine deficiency could be corrected as well. PMID- 1876605 TI - Pancreatitis caused by measles, mumps, and rubella vaccine. AB - Acute pancreatitis may result from viral infections, including mumps, coxsackie B, Epstein-Barr, and varicella. However, viral pancreatitis has not been reported after immunization with viral vaccines. We report the occurrence of acute pancreatitis in an adult who had received measles, mumps, and rubella II vaccine (MMR II). PMID- 1876606 TI - Pancreas divisum. PMID- 1876607 TI - Amino acid variations at a single residue in an autoimmune peptide profoundly affect its properties: T-cell activation, major histocompatibility complex binding, and ability to block experimental allergic encephalomyelitis. PMID- 1876608 TI - Cerebral vascular effects of peptide histidine methionine in canine and bovine species. AB - Peptide histidine methionine (PHM) is a neuropeptide with structural homology to vasoactive intestinal peptide (VIP), itself a putative vasodilatory neurotransmitter. Intra-arterial administration of PHM caused a transient, dose dependent increase in canine vertebral artery blood flow in vivo. PHM was less potent in this effect than VIP. The interaction of PHM with the vasoconstrictor amines, norepinephrine, histamine, and serotonin, was examined using isolated strips of the bovine middle cerebral artery. PHM shifted the concentration response curves for vasocontraction by norepinephrine and histamine to the right but did not affect the vasocontraction induced by serotonin. These results suggest that PHM may have a role in the regulation of the cerebral circulation. PMID- 1876609 TI - Indometacin: renal handling and effects in the isolated perfused rat kidney. AB - We investigated renal handling and effects of indometacin on renal function in the isolated perfused rat kidney (IPK). Indometacin concentrations less than 2.5 ng/ml did not influence renal function, while higher concentrations caused a decrease in urinary flow and electrolyte excretion. The presence of 133 ng/ml prostaglandin E2 (PGE2) in the perfusate fully opposed these effects on kidney function. Only a small fraction of the filtered indometacin is excreted into the urine, indicating extensive reabsorption of the compound. This is probably a passive process, dependent on the tubular load, urinary pH and urinary flow. Indometacin accumulates extensively in the IPK, causing a kidney to perfusate ratio between 5 and 9. Accumulation decreased with increasing perfusate concentration. This can be explained by active secretion: increasing the perfusate concentration leads to a saturation of the active secretion and a decrease in the relative accumulation. We conclude that indometacin accumulates extensively in the IPK, that it affects kidney function and that this influence is probably caused by the inhibition of PGE2 synthesis. PMID- 1876610 TI - Depression and chronic fatigue. PMID- 1876611 TI - Depression and chronic fatigue in children. A masquerade ball. AB - Major depression disease is uncommon in children; it occurs mostly in children with a depressed parent or in children under major psychosocial stress such as physical or sexual abuse. Most depression in children is masked, i.e., the child presents with signs or symptoms such as headaches, abdominal pain, muscle weakness, vomiting, dizziness, hyperactivity, or school avoidance. Careful evaluation of the history is required to assist in the diagnosis. Some basic laboratory tests should be done to rule out organic disease. Psychiatric referral should be carried out after an appropriate evaluation. PMID- 1876612 TI - Depression, chronic fatigue syndrome, and the adolescent. AB - To summarize, CFS and depression present very real problems for adolescent patients, their families, and their physicians. The wealth of symptoms presented may signal the presence of any number of psychiatric or physiologic disorders. As part of the evaluation to rule out other maladies, the physician must identify the developmental issues and life stress events with which patients or their families are struggling. Helping patients to accept psychiatric referral to address these issues is indicated if it is thought that they may be contributing to the onset or maintenance of the symptoms. Referral is also indicated if a protracted clinical course evolves and the patient's normal course of growth and development appears to be in jeopardy. PMID- 1876613 TI - Exercise. Practical treatment for the patient with depression and chronic fatigue. AB - Exercise should be part of everyone's lifestyle, but may be a particularly important part of the treatment of patients with depression and chronic fatigue. It will reliably and consistently decrease feelings of tiredness and despondency, although it is seldom sufficient as a sole treatment intervention for such patients. When initiating an exercise program, a baseline assessment should be followed by an exercise prescription and an appropriate degree of patient education about exercise physiology. This should be followed, in addition to other treatment interventions, by regular follow-up visits to make appropriate adjustments; provide encouragement and motivation to continue; monitor weight, body fat, and nutrition; and assess the effectiveness of the program on the underlying problem. PMID- 1876614 TI - Depression and chronic fatigue in the high school student and athlete. AB - By presenting the salient aspects of a case study of a high school student athlete, we have attempted to show how participation in sports can negatively impact on self-concept, self-esteem, physical acceptance, and self-efficacy, thereby contributing to an overall feeling of inadequacy, helplessness, hopelessness, and ultimately leading to depression and chronic fatigue. An early maturer, this student experienced early success in several sports without a great deal of effort and investment, and derived much of his sense of being from the recognition and reinforcement accorded him by significant others, most notably from a father who placed a higher premium on success in athletics than on other equally worthwhile pursuits. When continued success was not forthcoming, and as later-maturing peers caught up to and surpassed his athletic accomplishments, the student sought to protect his sense of self-esteem by rationalizing that his lack of success was due to a physical problem. He became obsessed with the thought that he was gradually losing his athletic identity and he lapsed deeper and deeper into a depressed state. His compulsive overtraining and starvation diet failed to produce his image of the "ideal body" that, of course, was unachievable because of his distorted view of reality. Ultimately, this behavior resulted in hospitalization for treatment of an eating disorder and clinical depression. Even a successful senior football season after his psychiatric care could not filter through his distorted perceptions and he could not cope with the thought of participating in another track and field season and having his performance bested by others whom he had once handily beaten. Thus, once again, he engaged in self protective behavior and sought verification from sportsmedicine professionals. Diagnosis of Tom's condition was possible only through the collaborative efforts of the athletic trainer, physical therapist, sport psychologist, and family physician. Professionals involved in sportsmedicine must be aware of the critical role that highly valued activities like sports play in the psychosocial development of adolescents. To the adult, these activities may seem trivial, frivolous, and removed from the "real world," but to the adolescent, they are an important source of self-esteem during a critical and volatile period of self concept edification. During a period of awakening sexuality and heightened awareness of their physical being, activities that emphasize the physical aspect of self gain prominence. Those who derive positive experiences benefit from enhanced feelings of physical self-efficacy and self-esteem.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1876615 TI - Depression and chronic fatigue in the college student-athlete. AB - For the most part, the intercollegiate athlete is a well-adjusted individual who demonstrates considerable vigor and well-being and less depression, anxiety, and fatigue when compared with nonathletic counterparts. The well trained athlete also demonstrates a personality that may be somewhat rigid, is strongly goal oriented, and strives for excellence. It is not unrealistic to expect that when confronted with diminished performance or success, athletes may be compelled to drive themselves harder to succeed. Such behavior typically leads to the phenomenon of overtraining, which can express itself in the form of chronic fatigue and depression. A number of other organic causes of chronic fatigue and depression must be excluded by careful evaluation and appropriate diagnostic testing. Although the evaluation of the athlete who presents with chronic fatigue and depression can be somewhat complex, a diagnostic framework has been outlined that may assist the clinician in the assessment of the athlete who presents with such complaints. PMID- 1876616 TI - Depression and chronic fatigue in the patient with heart disease. AB - Depression and chronic fatigue are frequently associated with heart disease. They may precede the onset of myocardial infarction, singly or together, and increase the morbidity and mortality of patients with a history of MI. Virtually all such patients have a transient depression, usually accompanied by anxiety, with onset soon after hospitalization. Although this depression is transient and usually abates spontaneously, it frequently warrants therapeutic intervention. Psychosocial and personality factors play a significant role in the recovery of a patient with a cardiac condition. The clinician must be alert for the effects of changing roles within the family and behaviors that may lead to chronic invalidism. Anxiety disorders, often combined with depression, may mimic cardiac disease and may result from it, leading to chronic fatigue and weakness. Proper diagnosis usually leads to considerable improvement. Cardiac drugs, in addition to many others, may produce depression and fatigue that may be misdiagnosed. Often, discontinuing or changing a medication will lead to marked diminution of such symptoms. Observational and listening skills are key ingredients of the "art" of medicine; they can lead to interventions that are not only therapeutic, but which improve the "quality" of life. PMID- 1876617 TI - Depression and chronic fatigue in cancer patients. AB - Fatigue is a very common symptom among cancer patients. It is crucial to diagnose those patients for whom the fatigue is a symptom of depression, and to treat them appropriately. The key to providing complete and satisfying care is to identify and address the psychologic, social, and medical vulnerabilities of each cancer patient. No one is in a better position to accomplish that than the primary physician. PMID- 1876618 TI - Depression and chronic fatigue in the patient with chronic pain. AB - Chronic benign pain is commonly associated with chronic fatigue and depression. Depression and chronic fatigue syndrome are also associated with each other and often include pain. Psychologic factors are prominent in these conditions, and they may share neurobiologic factors as well. Management requires separately addressing each component of patients' distress and usually includes physical rehabilitation, education, administration of nonhabituating medications and often counseling. Depression may be a favorable prognostic sign, as it suggests a treatable condition and provides incentive for recovery. PMID- 1876619 TI - Fatigue and depression in the patient in the intensive care unit. AB - The recognition, management, and treatment of fatigue and depression in the patient in the intensive care unit has been presented in a framework to allow consideration of intrapsychic, interpersonal, environmental, and disease factors that can be altered by various means. It is rare that fatigue so seriously complicates the primary illness as to be life threatening itself. Depression and delirium are associated with increased morbidity and mortality on their own; therefore, prompt attention to major depressive disorders and organic effective disorders is necessary. Through it all, attention to the person who has the disease with fatigue, depression, or both is essential. PMID- 1876620 TI - Depression, chronic fatigue, and the premenstrual syndrome. AB - Depression, chronic fatigue, and premenstrual syndrome often coexist in women seeking treatment for premenstrual distress. A reliable diagnosis can be made by prospectively rating symptoms for two cycles, taking a careful history, performing physical and gynecologic examinations, and obtaining basic laboratory test results and a psychosocial evaluation. Appropriate dietary, hormonal, or antidepressant treatment provided in a caring and competent manner can benefit many women suffering from this otherwise disabling/condition. PMID- 1876621 TI - Chronic fatigue and depression in the ambulatory patient. AB - Fatigue, pain, and emotional upset remain the most common problems affecting humanity and for which we still know so very little. Chronic fatigue syndrome is most likely a number of as yet unproven various undifferentiated illnesses that are exceedingly difficult to distinguish from depression. There probably is a subset of patients with CFS who do have true immune dysfunction and persistent viral infection, and this particular group of patients should be further investigated. This group is the minority of patients who present with chronic fatigue. Although chronic fatigue syndrome may be the result of an organic illness in psychologically susceptible individuals, it remains most important to assess underlying psychologic factors that then need to be addressed. These factors may very likely have a profound effect on immune function, but more research is needed in this area. The diagnostic evaluation of patients with chronic fatigue syndrome should initially focus on causes for fatigue other than Epstein-Barr viral infection. Significant underlying medical conditions should be ruled out, and extensive inquiry into symptoms suggestive of depression and anxiety should be aggressively pursued. Treatment should include psychiatric support and counseling, good nutrition, adequate rest, and a gradual increase in activity. Anti-inflammatory agents and serotonin-replenishing antidepressants are helpful when muscle pain and tenderness are a major part of the patient's symptoms. Psychoactive drugs are useful when indicated. Low doses of antidepressants such as doxepin (10-25 mg at night) are generally well tolerated and have shown efficacy in numerous patients, although there are no reports of controlled trials. PMID- 1876622 TI - Treatment of depression. New pharmacologic approaches. AB - Recurrent major depression is an underdiagnosed, undertreated mood disorder that affects approximately 10 million Americans. Although the tricyclic antidepressants are the oldest and best studied class of antidepressant medications available, their use is routinely compromised by unsatisfactory pharmacokinetic and side-effect profiles. The newer antidepressant medications have longer half-lives and are less likely to produce side effects. The prototypes of the newer antidepressants are bupropion (Wellbutrin) and fluoxetine (Prozac). Fluoxetine distinguishes itself in that its half-life is 2 to 3 days, whereas the mean half-life of buproprion and the tricyclics are 10 to 14 hours. For this reason, fluoxetine is routinely administered once daily in the morning. Both of these agents bind to the cholinergic, histaminergic, and alpha-1 adrenergic receptors with minimal affinity, and are less likely to yield clinically significant side effects. The use of the newer antidepressants has led to improved patient compliance and physician acceptance. PMID- 1876623 TI - Depression and chronic fatigue. Indications for psychiatric consultation. AB - Symptoms of fatigue and the fatigue syndrome itself are familiar complaints heard by nonpsychiatric physicians in the general hospital. The nature of these complaints is often diffuse and frequently conceals atypical psychiatric disorders. In the general hospital setting, consultation psychiatry, which functions as the interface between psychiatry and these medical practitioners, is ideally situated to assist in the assessment and management of these patients. This article reviews the methods of approach that psychiatric consultants can use to assist their nonpsychiatric colleagues in identification and referral for problems involving fatigue. In addition, a brief review of diagnosis, management, and treatment of such patients is given. PMID- 1876624 TI - Depression and fatigue in the primary care physician. AB - Fatigue is a symptom that is found in a variety of psychiatric disorders. The nature of a physician's life may foster such symptoms that can be either a reaction to work or a sign of an emotional disorder. This article summarizes various developmental stages that can lead to such problems. These difficulties may also be found in the physician's family and can be easily overlooked. PMID- 1876625 TI - Relationship of lateral ventricular size to psychophysiological measures and short-term outcome. AB - To examine clinical and psychophysiological correlates of lateral ventricular size, computerized tomographic (CT) scans were obtained on a sample of 88 patients who had experienced their first psychotic episode. Patients met DSM-III criteria for schizophrenia, schizophreniform disorder, or affective disorder with psychotic features. For patients with schizophrenia, large lateral ventricles were associated with unfavorable outcome. No association between outcome and ventricular size was found in patients with affective or schizophreniform disorder. Patients with mood disorders who had large ventricles consumed significantly greater amounts of alcohol than those with small ventricles. No differences were found between patients with large or small ventricles in premorbid functioning, smooth pursuit eye tracking, or electrodermal activity. PMID- 1876626 TI - Atenolol in premenstrual syndrome: a test of the melatonin hypothesis. AB - Eleven patients with prospectively documented premenstrual depression were given 100 mg atenolol or placebo daily to suppress melatonin secretion during the symptomatic premenstrual phase of the menstrual cycle. There was no significant improvement in mood following treatment with atenolol vs. placebo. These findings suggest that bright light may exert antidepressant effects in patients with premenstrual syndrome through mechanisms other than melatonin suppression and that atenolol does not appear to be a viable treatment modality for the majority of patients with premenstrual depression. PMID- 1876627 TI - Disengagement of attention in schizophrenia. AB - We compared covert shift of visual attention in patients with schizophrenia or bipolar disorder, both in states of remission, to normal controls to examine the persistence of lateralized attentional deficits into nonpsychotic states. Although patients were slower in all conditions than normals, there was no difference in pattern of attentional shift among the groups. This suggests that the left-hemisphere deficit in shift of covert attention in schizophrenia may be limited to periods of florid illness. PMID- 1876628 TI - Noradrenergic function in obsessive-compulsive disorder: behavioral and neuroendocrine responses to clonidine and comparison to healthy controls. AB - To evaluate noradrenergic (NE) function in obsessive-compulsive disorder (OCD), behavioral, physiological, and neuroendocrine responses to the alpha 2-adrenergic agonist clonidine were examined in 18 patients with OCD and 10 healthy subjects. Subjects received single i.v. doses of 2 micrograms/kg of clonidine administered under double-blind, placebo-controlled, random-assignment conditions. Following clonidine, but not following placebo, patients transiently experienced a significant reduction of obsessions and compulsions. Significant drowsiness and a reduction in anxiety were also noted, but the antiobsessional effect appeared independent of the soporific and antianxiety effects. Growth hormone (GH), cortisol, and 3-methoxy-4-hydroxyphenylglycol responses to clonidine did not differentiate patients from healthy controls. Blood pressure and pulse in response to clonidine did not differ between groups. Improvement in OCD symptoms after clonidine significantly correlated with GH response to clonidine, suggesting specific noradrenergic mediation. This finding lends only partial support for a primary defect of noradrenergic function in OCD. PMID- 1876630 TI - MRI-induced headache. PMID- 1876629 TI - Mania: sympathoadrenal function and clinical state. AB - We investigated sympathoadrenal and sympathetic nervous system activity, catecholamine disposition, and clinical state in 19 hospitalized manic patients. Severity of the core manic syndrome, anxiety, and hostility correlated with 24 hour urinary excretion of epinephrine relative to its metabolites, but only weakly with norepinephrine. Agitation, however, correlated most strongly and significantly with norepinephrine. Eight of the patients had mixed states: concurrent manic and depressive syndromes. There were no differences between mixed and pure manic patients with respect to catecholamine or metabolite excretion or precursor/product ratios, but mixed manic patients tended to have higher excretion of norepinephrine and had increased variance with respect to catecholamine measures. These data suggest that the function of the adrenal medulla, whether directly or indirectly, is important in the symptoms of both mixed and pure mania. PMID- 1876631 TI - Doubt about evidence for a schizophrenia gene on chromosome 5. PMID- 1876632 TI - Epidemiological study of eating disorders: time for a change of emphasis. PMID- 1876633 TI - Amnesia: lesion location and functional deficit--what is the link? PMID- 1876634 TI - Karl Philipp Moritz' Journal of Empirical Psychology (1783-1793): an analysis of 124 case reports. AB - Karl Philipp Moritz edited Gnothi Sauton, the Journal of Empirical Psychology (1783-1793), which stands as the first of numerous psychological and psychiatric periodicals. We evaluated 124 psychiatric or neurological case reports from the journal according to modern diagnostic criteria and present a brief outline of the contributors' and patients' sociodemographic characteristics, selected case reports and the surmised risk factors. A reliable diagnostic reassignment of the well-described cases was feasible; this may indicate that patients retain similar psychiatric disturbances over the centuries. As in the popular literature of the period, examples of 'sentimental students' and 'desperate soldiers' represented the most frequently discussed, prototypical high-risk personalities in the Journal, which marked the step from literature to empirical science. The influences of this case material upon contemporary psychiatric writing and thought are reviewed. PMID- 1876635 TI - Blunting of neuroendocrine responses to infusion of L-tryptophan in women with perimenstrual mood change. AB - The neuroendocrine response to L-tryptophan infusion was measured at two stages of the menstrual cycle, premenstrually and postmenstrually, in 13 women with and 13 women without premenstrual depression (the MC and NMC groups respectively). Previous studies have shown that in non-depressed women, this challenge test results in an increase in circulating prolactin and growth hormone. In depressed women both responses are blunted. In this study the growth hormone and cortisol responses were smaller in the MC group than the NMC group on both occasions. The prolactin response was blunted premenstrually compared with postmenstrually in both groups. These findings suggest that women who experience premenstrual depression may have neuroendocrine abnormalities throughout the cycle. The neurotransmitter abnormalities reflected in these altered endocrine responses appear to interact with neuroendocrine changes that normally occur premenstrually resulting in a vulnerability to depression at that phase of the cycle. PMID- 1876636 TI - A further exploration of the relationships between immune parameters and the HPA axis activity in depressed patients. AB - In order to investigate the relationship between the immune apparatus and the hypothalamic-pituitary-adrenal (HPA)-axis activity in depressed patients, we measured in vitro lymphocyte responses to the mitogens Phytohaemagglutinin (PHA), Pokeweed (PWM) and Concanavalin A (Con A) and 8 a.m. baseline cortisol values in plasma, free cortisol excretion in 24 h urine (UFC), basal and post-dexamethasone beta-endorphin values. Major depressed patients with melancholia/psychotic features exhibited a significantly lower mitogen-induced blast transformation as compared to minor and simple major depressed patients. The lymphocyte responses to the three mitogens were significantly inversely related to baseline cortisol values and postdexamethasone beta-endorphin values. The proliferative capacity of lymphocytes to stimulation with PHA and PWM was significantly and positively related to UFC excretion. Up to 45% of the variance in the immune-responses to the mitogens was explained by the baseline cortisol, post-dexamethasone beta endorphin and UFC values. PMID- 1876637 TI - Centrum semiovale white matter CT changes associated with normal ageing, Alzheimer's disease and late life depression with and without reversible dementia. AB - A standardized, reliable means of assessing CT attenuation numbers in the centrum semiovale and surrounding grey matter was developed. This was applied to cranial CT scans of 60 normal controls (36 aged greater than 60 years), 25 elderly patients with major depression (14 of whom had the dementia syndrome of depression), and 10 patients with Alzheimer's disease (AD). Subjects received neuropsychological evaluation. Centrum semiovale (CSO) CT attenuation numbers decreased with increasing age for both white and grey matter. White matter attenuation values best discriminated elderly controls from the three patient groups. Both white and grey matter CSO attenuation values correlated with performance on a number of cognitive tasks. PMID- 1876638 TI - Nature, nurture and depression: a twin study. AB - We studied a series of twins systematically ascertained through 214 probands (84 monozygotic, 130 dizygotic) who had had one or more episodes of hospital-treated major depression. A variety of definitions of depression were applied to the co twins all of which resulted in (a) markedly higher rates of disorder than are found in the general population, (b) significantly higher monozygotic than dizygotic concordance. The results of applying a simple additive model in which depression is considered as a threshold trait suggested that both genetic factors and shared family environment make substantial and significant contributions to the familiality of depression. PMID- 1876639 TI - Coping: a genetic epidemiological investigation. AB - This study examines data on self-report coping behaviour, life events and symptoms of anxiety and depression in a general population sample of 827 female twin pairs. Factor analysis identified three almost uncorrelated coping factors: turning to others; problem solving; and denial. Turning to others and problem solving were negatively and denial was positively related to levels of anxiety and depression. Turning to others and problem solving buffered the depressogenic and anxiogenic effects of stressful life events, while denial exacerbated the anxiogenic effects of life events. Structural equation model-fitting indicated that twin resemblance in turning to others and problem solving could be explained entirely by genetic factors with an estimated heritability of 30 and 31%, respectively. For denial, twin resemblance could be best explained by familial environmental factors accounting for 19% of the total variation. Genes may affect the vulnerability to psychiatric disorders in part by influencing coping behaviour. PMID- 1876640 TI - Psychiatric symptoms, personality and ways of coping in chronic fatigue syndrome. AB - This study aimed to investigate the psychological characteristics of chronic fatigue syndrome (CFS: Holmes et al. 1988). A battery of psychometric instruments comprising the General Health Questionnaire (GHQ), the Beck Depression Inventory (BDI), the Minnesota Multiphasic Personality Inventory (MMPI) and the Lazarus Ways of Coping (WoC) inventory, was administered to a sample of clinically defined CFS sufferers (N = 58), to a comparison group of chronic pain (CP) patients (N = 81) and to a group of healthy controls matched for sex and age with the CFS sample (N = 104). Considerable overlap was found between CFS and CP patients at the level of both physical and psychological symptoms. This raises the possibility that CFS sufferers are a sub-population of CP patients. However, while there was some commonality between CFS and CP patients in terms of personality traits, particularly the MMPI 'neurotic triad' (hypochondriasis, depression and hysteria), CFS patients showed more deviant personality traits reflecting raised levels on the first MMPI factor, emotionality. Moreover, results were not consistent with the raised emotionality being a reaction to the illness, but rather were consistent with the hypothesis that emotionality is a predisposing factor for CFS. The majority of CFS patients fell within four personality types, each characterized by the two highest MMPI scale scores. One type (N = 20) reported a lack of psychological symptoms or emotional disturbance contrary to the overall trend for the CFS sample. This group conformed to the ICD 10 classification of neurasthenia. PMID- 1876641 TI - Factors affecting survival in Alzheimer's disease. AB - Factors affecting survival of 178 patients diagnosed using NINCDS/ADRDA criteria for Alzheimer's disease were studied. All patients were drawn from the Camberwell Health Authority Area and so were a representative sample of subjects from a clinical old age psychiatry service. The mortality rate of the sample was 3.5 times that expected after adjustment for age. Younger subjects had a higher standardized mortality ratio than older subjects. The cumulative three-year mortality of the sample was 47%. Factors shown to be associated with a reduced survival included: increasing age, longer duration of illness, male sex, presence of physical illness, poor cognitive function, observed depression and absence of misidentification syndromes. Apraxia was a stronger predictor of early death than aphasia or dysmnesia. PMID- 1876642 TI - Season of birth for Alzheimer's disease in the Southern Hemisphere. AB - Season of birth was compared in 170 clinically diagnosed cases of Alzheimer's disease (AD) in Australia and 170 matched controls. A further comparison was made with a large population sample of the elderly. No evidence for seasonality of birth was found. This finding held not only for the total series of 170 cases, but also for the 143 born in the Southern Hemisphere, for sporadic cases, and for those with earlier onset. These negative findings in Australia contrast with the positive finding in London by Philpot et al. (1989). PMID- 1876643 TI - The psychobiology of minor head injury. AB - Twenty-six consecutive admissions to an accident and emergency unit with minor head injury were examined. This was defined as a head injury warranting brief in patient overnight stay but with a post-traumatic amnesia of less than 12 hours. Each patient had a neurological examination, a post-traumatic symptom check list completed, EEG power spectra analysis and auditory brain stem-evoked potential recordings, and a four-choice reaction-time measurement. These assessments were repeated six weeks later. Six months after the head injury a symptom check list was completed and four-choice reaction time measured again. Post-traumatic symptoms are persistent in half of all patients at six weeks and six months follow-up. The EEG power spectra showed a significant change in theta power between the first recording and the second one at six weeks, with relative reduction being noted. Approximately half of all patients had significant delays in brain stem conduction time at day 0. There was a trend towards a decrease in brain stem conduction time at six weeks, though in almost half the brain stem conduction time still remained abnormal at six weeks. Head-injured patients had prolonged choice reaction times at day 0 with serial improvement between then and six months, though the values at six weeks were still significantly longer than healthy controls. It is suggested that these findings reflect both cortical and brain stem damage following minor head injury, the brain stem damage being more persistent. There appear to be three patterns of recovery, half recovering within six weeks, a minority persisting over six months with persisting brain stem dysfunction and less than a third showing an exacerbation of symptoms with no evidence of brain stem dysfunction, the exacerbation being possibly a consequence of psychological and social factors. PMID- 1876644 TI - Occurrence of schizotypal and borderline symptoms in parasuicide patients: comparison between subjective and objective indices. AB - Seventy-six patients were interviewed within a week of admission following a parasuicide episode. Axis II diagnosis on DSM-III was made for schizotypal, borderline, histrionic, and antisocial personality disorder. In addition patients completed a self-rating questionnaire, the Schizotypy Questionnaire of Claridge & Broks (1984), which assesses schizotypal and borderline personality traits. The objective and subjective indices of schizotypal and borderline symptoms correlated significantly but allocation of patients to a diagnosis missed several patients who nevertheless rated themselves as having a high frequency of these symptoms. There was an asymmetry of symptom pattern reminiscent of Foulds & Bedford's (1975) hierarchy model. The presence of schizotypal symptoms appeared to be higher in the hierarchy: they predicted borderline symptoms, but a high frequency of borderline symptoms did not necessarily predict schizotypy. We suggest that the occurrence of schizotypal symptoms should become a more explicit focus of clinical assessment and treatment of these patients, especially those who repeatedly harm themselves and we suggest ways in which cognitive therapies may be adapted to do this. PMID- 1876645 TI - Parasuicide and the lunar cycle. AB - Admissions to hospital following parasuicide in one city over eighteen years exhibit a cyclical variation apparently synchronized with the lunar quarters. The effect would only account for approximately 0.7 out of the average of 46 parasuicides per 100,000 adults per lunar cycle (95% CI 0.6-0.8), and fails to reach statistical significance. PMID- 1876646 TI - Perceived interpersonal risk factors of non-endogenous depression. AB - In a case-control study, two potential interpersonal risk factors of non endogenous depression, namely a patient's perception of their current intimate partner as dysfunctional and a patient's recall of exposure to previous deprivational parenting, were quantified. The interpersonal characteristics of the partner were assessed principally by a brief self-report questionnaire, the Intimate Bond Measure (IBM). By cross-sectional and longitudinal comparison of this instrument with other interview-derived and self-report measures, the convergent, discriminant and predictive validity of the IBM in depressed patients was established. Further, little evidence of any distorting effect of depressed mood or neuroticism was detected. The perception of the current intimate partner as dysfunctional imparted a risk to non-endogenous depression of at least five times, while reported exposure to parental 'affectionless control' was quantified as a four times' risk. Importantly, IBM care scores predicted the course of the depressive disorder over a six-month period. PMID- 1876647 TI - Psychosocial family intervention in schizophrenia: a review of empirical studies. AB - This paper reviews the recent empirical studies on psychosocial family intervention in schizophrenia. Six family educational intervention studies and five more intensive family work studies with 2-year follow-up have been included. A series of questions is asked relating to the effects of such interventions, the efficacy of the different educational models, the active ingredients of these multi-component treatment packages, and the contribution of this new generation of studies to our understanding of the mechanisms through which these interventions work. Suggestions for further research are made. Finally, from the published manuals, the common components of these diverse, multi-component treatment packages of different family-intervention studies are identified. PMID- 1876648 TI - Object chaining and thought disorder in schizophrenic speech. AB - The phenomenon of object chaining was investigated to determine its relationship to thought disorder in schizophrenia. Samples from thought-disordered schizophrenics (N = 12) and controls (10 non-thought-disordered schizophrenics and 10 normals) were analysed. Using the object subject ratio (OSR) to measure object chaining, we found higher OSRs in the speech of thought-disordered subjects than in that of subjects free of thought disorder. Object chaining correlated with low predictability of speech. We conclude that object chaining is associated with reduced speech comprehensibility and probably contributes to the judgement that thought disorder is present. PMID- 1876649 TI - Follow-up studies of anorexia nervosa: a review of four decades of outcome research. PMID- 1876650 TI - The incidence and prevalence of anorexia nervosa and bulimia nervosa in primary care. AB - General practitioners using DSM-III criteria have studied the incidence and prevalence of anorexia nervosa and bulimia nervosa in a large (N = 151,781) representative sample of the Dutch population. The incidence rate for anorexia nervosa is 6.3 and for bulimia nervosa 9.9 per year per 100,000 population. The prevalence of bulimia nervosa is three times higher in larger cities than in smaller urbanized or rural areas, while anorexia nervosa is found with almost equal frequency in areas with a different degree of urbanization. PMID- 1876651 TI - DSM-III compulsive personality disorder: an epidemiological survey. AB - A two-stage probability sample of community subjects was developed with a full psychiatric examination employing DSM-III criteria in conjunction with the Epidemiological Catchment Area (ECA) survey conducted in Baltimore, MD. This report details the observation on those subjects diagnosed with compulsive personality disorder and compulsive personality traits. The results indicate that this condition has a prevalence of 1.7% in a general population. Male, white, married and employed individuals receive this diagnosis most often. Our data suggest a dimensional rather than categorical character for this disorder. The disorder imparts a vulnerability for the development of anxiety disorders. PMID- 1876652 TI - Determinants of somatization in primary care. AB - This study explores possible determinants of somatization in primary care. Hypotheses were tested on samples of 'somatizers', 'psychologizers' and controls recruited by epidemiological procedures. Although 'somatizers' were found to be similar to 'psychologizers' in many respects, they were (i) less depressed; (ii) reported lower levels of social dissatisfaction, social stress and less dependence on their relatives; (iii) more likely to have an unsympathetic attitude towards mental illness and less likely to consult a doctor about psychological symptoms, and (iv) more likely to have received medical in-patient care as an adult before they had consulted their doctor with their current illness. These findings are discussed in the context of previous research. PMID- 1876653 TI - General practitioner referral to specialist psychiatric services: a comparison of practices in north- and south-Verona. AB - Specialist psychiatric services run by the Italian National Health Service are mainly hospital-based in North-Verona and community-based in South-Verona. Ninety two GPs from both areas participated in a one-day survey of their provision of psychiatric care, and this paper focuses on socio-demographic and clinical variables associated with specialist psychiatric referral. The one-day prevalence figure for GP referral to specialist psychiatric services was 7.3% (17.6/10,000): the figures did not differ between the sexes or between the two areas. Whereas in North-Verona 49% of the patients referred were sent to the two local hospital based public services and 51% to other agencies (mainly to private psychiatrists), in South-Verona 71% of referrals were to the community-based public service. Log-linear analysis showed that past psychiatric history, psychological presenting complaint, social problems and GPs' psychiatric diagnosis exerted positive joint main effects on GP referral to specialist psychiatric services, and that diagnosed organic illness had a negative effect in this regard. In the presence of a psychological complaint, a psychiatric diagnosis proved to be quite unimportant, so that those without a psychiatric diagnosis were just as likely to be referred as those with one. However, in the absence of a psychological complaint a GP diagnosis of depression greatly increased the risk of referral. Though the type of psychiatric service proved not to be an important determinant of GP referral to specialist psychiatric services it influenced the GPs' choice of referral agency. PMID- 1876654 TI - A three-year follow-up of psychiatric morbidity in urban and rural primary care. AB - Follow-up by examination of medical and psychiatric records was carried out on 357 patients with conspicuous psychiatric morbidity in two general practices three years after clinical and personality assessment using structured interview schedules. One practice was an inner-city urban one and the other was rural. Full follow-up data over the 3-year period was available for 301 patients (84.3%). After three years patients with personality disorder and those in the urban practice had greater morbidity, more contacts with all levels of the psychiatric service and more psychotropic drugs, particularly benzodiazepines. Despite this increased morbidity, the number of consultations with the general practitioner for psychiatric illness was no higher in the urban group and those for medical illness were significantly higher in the rural one. The implications of the findings are discussed with particular reference to developments in community psychiatric care. PMID- 1876655 TI - Life events, social problems and physical health status as predictors of emotional distress in men and women in a community setting. AB - The main aim of this study was to construct logistic models of emotional distress (defined as a GHQ-30 score of 6 or greater) in a community sample of 226 men and 225 women. The independent variables included were: sociodemographic characteristics, physical health status, social problems and undesirable life events. Univariate comparisons showed that in both sexes undesirable life events and social problems were associated with emotional distress; in men the presence of physical symptoms and widowed, separated or divorced status also showed such an association. Separate logistic regression models for men and women confirmed the importance of undesirable life events and social problems as predictors for emotional distress. In women there was also a significant interaction effect between the two variables on emotional distress. Sociodemographic characteristics and physical health status did not exert a statistically significant effect in these models. PMID- 1876656 TI - In sickness and in health: associations between physical and mental well-being, employment and parental status in a British nationwide sample of married women. AB - Many studies have been published which have examined the relationship between paid employment and women's health. As employment outside the home is likely to have differential effects for women with different family commitments, further analysis taking account of the association between paid employment and household circumstances is necessary. Using data from a large, representative British sample, this paper examines the effects of interactions between paid employment, social class, and parental status on women's health. The results show differential effects of these variables on physical and mental health. The most important influence on women's mental health (as measured by the 30-item General Health Questionnaire) is the age of their youngest child; women with children under five are most likely to show signs of psychological disturbance. With respect to physical health, age of the youngest child has no significant effect, but there is an interaction between employment status and social class. Paid employment, particularly full-time work, is associated with good physical health for middle-class women but not for working-class women. PMID- 1876657 TI - The use of the Clinical Interview Schedule for the evaluation of mental health in the aged community. AB - As a part of a survey to study the health and living conditions of the elderly population, a random sample of residents aged 65 and over are examined using the Clinical Interview Schedule (CIS) in order to evaluate their psychiatric status. The aim of this study is to evaluate this standard method of assessment as a case identification instrument in our country. The schedule was completed by 91 subjects. It is easily administered, easily scored, and economical on time. Its completion rate is high. The weighted total scores (WTS) range from 0 to 48. Using the case criteria defined by Cooper & Schwarz (1982), 27 subjects (30%) are considered cases and 64 (70%) are regarded as non-cases. The sensitivity coefficients for the WTS are examined against the overall severity rating at different cut-off points. The optimum cut-off can be anywhere between 16 and 20 points. The WTS has higher validity coefficients to detect the following diagnostic categories (sensitivity, specificity): normals (100%,-); personality (100%, 92%) and affective disorders (100%, 75%). In general the CIS items are given low ratings. Psychotic symptoms are rarely found in this sample. One main problem arose: the item depersonalization is misunderstood by some patients probably because of interpreting it as an upsetting memory disturbance. PMID- 1876658 TI - Effects of food FR and food deprivation on disruptions in food-maintained performance of monkeys during phencyclidine withdrawal. AB - Six rhesus monkeys self-administered orally-delivered phencyclidine (PCP) and water under concurrent fixed-ratio (FR) 8 schedules. Liquids were available during three 6.5-h periods daily preceded by 1-h components when food was available under an FR 64 (lever press) schedule. After 10 days of stable behavior, water was substituted for PCP for 8 days. PCP was subsequently reinstated, and this PCP withdrawal sequence was repeated using different food FR values (64, 128, 256, 512 and 1024). Each time the food FR was changed behavior was allowed to stabilize for at least 10 days. Under all FR values food maintained responding decreased markedly during PCP withdrawal, with a gradual recovery over the next 8 days. As the FR value increased from 64 to 1024 there was a parallel shift downward in food-maintained performance. When PCP was reinstated, food-reinforced responding generally returned to baseline rates during the first few days. In a second experiment monkeys were tested for PCP withdrawal effects under relatively food deprived or food satiated conditions under both an FR 512 and 1024 schedule of food delivery. The results showed that the decrease in food-maintained responding during withdrawal was inversely related to the total amount of food consumed during the control period. The results of these experiments indicate that manipulation of both the response requirements for food (FR) and the total amount of food available (food deprivation/satiation) alters the magnitude of response disruptions during PCP withdrawal. PMID- 1876659 TI - Different patterns of behavior produced by haloperidol, pentobarbital, and dantrolene in tests of unconditioned locomotion and operant responding. AB - Three motor-impairing drugs with different putative mechanisms of action (haloperidol 0.00, 0.075, 0.15, 0.30 mg/kg IP; pentobarbital 0.00, 4.5, 9, 12 mg/kg IP; and dantrolene 0.00, 5, 7.5, 10 mg/kg IP) produced strikingly similar patterns of dose-dependent attenuation in unconditioned locomotor behavior. However, the same drugs and doses produced highly divergent patterns of disruption when tested using different groups of rats in a food-rewarded operant task, which included both response initiation and maintenance components (FR1-FR1 two lever chain). Haloperidol animals began the session as fast as vehicle animals and slowed dose-dependently across trials; pentobarbital animals started off significantly slower than controls but soon achieved comparable speeds; and dantrolene animals were slower throughout the session. These results suggest that the observed neuroleptic-induced deterioration in responding over trials, especially in response initiation, was not simply a result of motoric disruption. Rather, the profile of this deterioration is consistent with the anhedonia hypothesis of neuroleptic action and supports the view that dopamine neurons are involved in the biological basis of food reward. PMID- 1876660 TI - Opiate antagonists reduce cocaine but not nicotine self-administration. AB - Rats were trained to self-administer cocaine in 1-h sessions on a fixed ratio 5 (FR5) schedule of reinforcement. Acquisition was carried out at a unit dose of 0.3 mg/kg and responding was then stabilized at cocaine doses of 0.1, 0.3, and 1.0 mg/kg/infusion. Pretreatments with naltrexone (0.1-10 mg/kg, SC) 20 min prior to the start of self-administration sessions resulted in decreases in cocaine self-administration at doses of 0.1 and 0.3 mg/kg/infusion, but not at 1.0 mg/kg/infusion. Decreases depended on the dose of naltrexone used, with greater decreases in self-administration occurring at higher antagonist doses. In addition, treatment with the opiate antagonist naloxone also reduced cocaine self administration at a unit dose of 0.3 mg/kg. A group of rats trained to self administer nicotine at a dose of 0.03 mg/kg/infusion on the same schedule of reinforcement was unaffected by naltrexone treatment. These results may indicate that an endogenous opiate system plays a role in cocaine reinforcement. PMID- 1876661 TI - Selective dopamine antagonists reduce nicotine self-administration. AB - The effects of selective D1 (SCH23390) and D2 (spiperone) dopamine antagonists, as well as of haloperidol, were examined on nicotine self-administration, food maintained responding, and locomotor activity in rats. Antagonists reduced both operant responding and locomotor activity. Response patterns indicated that motor impairment was not the cause of the decreases, since responding was attenuated only in the latter half of operant sessions. Locomotor activity scores were significantly reduced by SCH23390, but not by spiperone. The effects of dopamine antagonists on nicotine self-administration are different from the effects of these antagonists on cocaine self-administration. Results are discussed in terms of the role of dopamine in drug reinforcement versus its role in sensorimotor integration. PMID- 1876662 TI - Tolerance to the analgesic, but not discriminative stimulus effects of morphine after brief social defeat in rats. AB - One of the most prominent consequences of defeat in a social confrontation is a long-lasting tolerance-like insensitivity to the analgesic effects of opiates, even when only small short-lived changes in nociception are detectable during the acute social stress. The present experiments examined (1) which kinds of social experiences lead to morphine tolerance, (2) whether or not the morphine tolerance in defeat-experienced rats extends from the analgesic effects to the discriminative stimulus and rate-decreasing effects of morphine, and (3) how long morphine tolerance lasts after a defeat experience. After five brief social confrontations including attack and threat by a resident rat leading to submission or defeat of the intruder, the latter exhibits marked tolerance to the analgesic effects of morphine, but not to the discriminative stimulus or behaviorally suppressive effects. Changes in social housing did not alter morphine's behavioral effects. Tolerance to the analgesic morphine effects was detected for 2 months after the defeat experience, whereas the discriminative stimulus and rate-decreasing effects were closely similar to those before defeat. This pattern was seen in animals for whom discriminative stimulus training with morphine was suspended after defeat as well as in those for whom it continued. In additional defeated and non-defeated animals, morphine's effects on the acoustic startle reflex was assessed. In contrast to the tail flick reflex to a noxious heat stimulus, the acoustic startle response remained unaffected by defeat experience or by morphine (up to 30 mg/kg). The long-lasting and large degree of tolerance after brief social defeat experiences appears to be limited to the analgesic effects of morphine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876663 TI - Ultrasounds during morphine withdrawal in rats. AB - Ultrasounds (US) in rats may communicate affective states, as they occur only in highly significant situations such as maternal care, sex and aggression. Withdrawal from morphine is a manipulation which dramatically alters autonomic, somatic and motor functions; the present experiment demonstrated the production of US in this context and the influence of previous social experience in their production. Sixty male Long-Evans rats with distinct social experiences (social inexperience, defeat or copulation) underwent 72 h of continuous morphine exposure (4 x 75 mg morphine or placebo pellets) and subsequent withdrawal. The rats were observed for 10 min in equally treated pairs and while solitary at 6, 24 and 96 h after pellet removal. US were emitted by all groups and consisted primarily of two distributions of pure tone whistles with little frequency modulation: 1-2 s 21-25 kHz ("low") signals and the more prevalent 0.02-0.1 s 44 52 kHz ("high") signals. Morphine withdrawn rats lost weight, displayed wet dog shakes, were hypoactive and emitted threefold more US vocalizations with a fourfold greater duration than placebo controls. Defeat-experienced morphine withdrawn rats were more hypoactive than either socially inexperienced or copulatory experienced rats while increasing vocalization rates and total duration. This increased duration of ultrasounds included a shift in the distribution of individual US durations from less than 0.3 s to greater than 1.0 s. US are readily emitted at high rates in morphine withdrawn laboratory rats, which may implicate an opioid involvement in their generation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876664 TI - Influence of acute and chronic haloperidol treatment on dopamine metabolism in the rat caudate-putamen, prefrontal cortex and amygdala. AB - The present study investigated the actions of single and repeated injections of the classical antipsychotic drug, haloperidol (1 mg.kg-1 IP), on dopamine (DA) metabolism in three distinct rat brain regions, namely the prefrontal cortex, amygdala and caudate-putamen (CP), using a high-performance liquid chromatographic assay. Acute administration of the drug caused significant elevations in concentrations of two major DA metabolites in all three areas studied. Less marked acute increases were seen in the CP following 10 days of repeated haloperidol treatment. However, in both the prefrontal cortex and the amygdala, the development of such "tolerance" was somewhat delayed in comparison, occurring only after a 22-day treatment schedule. The amygdala displayed the greatest degree of neurochemical tolerance, returning to control values by day 22 of chronic treatment. When allowance was made for the withdrawal effects of antipsychotic drug administration, a genuine tolerance phenomenon was observed in all three areas examined. These data suggest that if neurochemical tolerance is a prerequisite for functional DA receptor blockade and hence therapeutic efficacy, then both the prefrontal cortex and amygdala should be considered as potential therapeutic targets of haloperidol and perhaps antipsychotic drugs in general. PMID- 1876665 TI - Cholinergic stimulation of substantia nigra: effects on feeding, drinking and sexual behaviour in the male rat. AB - Previous studies have shown that cholinergic stimulation of the substantia nigra increases food intake but not other activities. The present experiments were undertaken to determine whether or not activities other than feeding could be stimulated if conditions were appropriate. Microinjections of the cholinergic agonist carbachol (0.5 micrograms/0.5 microliters each side) bilaterally into substantia nigra increased the consumption of dry spaghetti, and, in subsequent tests, changed sexual behaviour in male rats. Ejaculation, mount and intromission latencies were unaffected but intromission frequency (though not mount frequency) was reduced following cholinergic stimulation (experiment 1). In a second experiment, an increase in the consumption of 2.0% saccharin solution and lab chow was stimulated by intranigral carbachol while the intake of tap water, and locomotion, gnawing, grooming, rearing and sniffing were all unaffected. These data indicate that cholinergic stimulation of substantia nigra can affect activity for which there is a pre-existing tendency, regardless of its form. A possible role for nigral acetylcholine in the control of pars compacta dopamine containing neurones is discussed. PMID- 1876666 TI - Evaluation of a psychophysiological model of classical fear conditioning in anxious patients. AB - Skin conductance variables have been compared in 30 anxious patients and 30 controls to investigate the extent to which anxiety is associated with increased autonomic arousal, reduced habituation or enhanced aversive conditioning. Skin conductance level, variability (spontaneous fluctuations) and response amplitudes to tones were significantly greater in patients than controls. Habituation of skin conductance responses to a series of ten innocuous tones (80 dB, 1 s) did not differ between the groups. Aversively conditioned skin conductance responses were measured to a further series of ten tones after a conditioning trial in which a loud white noise (100 dB) followed tone 11. All subjects showed enhanced (conditioned) responses to the tones after the conditioning trial, but patients did not show greater conditioning than controls. The results indicate that anxious neurotic out-patients have greater sweat gland activity and reactivity than controls but fail to demonstrate differences in central mechanisms of habituation or conditioning. PMID- 1876667 TI - Characterization of a psychophysiological model of classical fear conditioning in healthy volunteers: influence of gender, instruction, personality and placebo. AB - Two experiments are described which evaluate the role of associative mechanisms and placebo effects on aversively conditioned skin conductance responses in groups of healthy volunteers. In both experiments, skin conductance level (SCL), variability (spontaneous fluctuations, SF) and amplitude (SCR) were recorded during a sequence of tone stimuli (80 dB, 1 s, 360 Hz). All the variables habituated during the first ten presentations of the tones. Tone 11 was immediately followed by a loud (100 dB) aversive brief (1 s) white noise UCS. The conditioning trial significantly enhanced SCRs to a further ten presentations of the tones and increased SCL and variability (SF). No enhancement of SCRs occurred when tone 11 was omitted and the UCS occurred in temporal isolation (experiment 1). Thus enhanced SCRs to tones following paired tone-noise presentation involves an associative mechanism. Increased "spontaneous" variability was shown to involve both conditioning and sensitization following the UCS. In both experiments females showed greater conditioned SCRs than males. In experiment 2 no effect of "anxiolytic" placebo could be discerned and there were no general relationships between questionnaires scores of extraversion or neuroticism with skin conductance measures in a group of 40 volunteers. The results question the role of conditionability and autonomic lability as major determinants of extraversion and neuroticism. These studies validate the use of the psychophysiological model of aversive conditioning in pharmacological studies of the mechanisms of habituation, conditioning and sensitization. PMID- 1876668 TI - Biphasic effect of tricyclic antidepressants on the release of norepinephrine from the adrenergic nerves of the rabbit heart. AB - The release of norepinephrine (NE) from the right atrium of the rabbit heart was used as a model to investigate biphasic effects due to tricyclic antidepressants, similar to those clinically observed in the treatment of depression and known as "therapeutic window". Strips of the atrium were loaded with 3H-NE, and then superfused by Krebs solution. The basal release and the electrical stimulation evoked release of 3H-NE were measured in the presence and absence of four clinically used tricyclic antidepressants: imipramine, amitriptyline, desipramine and nortriptyline. In addition, guanethidine, an adrenergic neuron blocker, was also studied. At lower concentrations (0.5-10 microM) tricyclic antidepressants increased, whereas higher concentrations (50-100 microM), inhibited the evoked release of NE. This inhibition was not prevented by the alpha2 adrenoceptor antagonist yohimbine, excluding the possibility of alpha 2 adrenoceptor-mediated inhibition of NE release. In higher concentrations the tricyclic antidepressants increased the basal release of NE in a Ca-independent way. Secondary amine derivatives were more potent inhibitors of the evoked release, and enhance the resting basal release of NE to a greater extent than the tertiary ones. Similarly, guanethidine (1-50 microM) also decreased the evoked release and increased the basal release of NE in a concentration dependent manner. Yohimbine failed to counteract the inhibition caused by guanethidine and the increment of the basal release was Ca-independent. It is concluded that the effect of tricyclic antidepressants in potentiating the release of NE is masked by their adrenergic neuron blocking properties, i.e. they inhibit the release of NE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876669 TI - Effects of nicotine on the acoustic startle reflex amplitude in rats. AB - The acoustic startle reflex was used to measure changes in sensorimotor reactivity in response to nicotine administration and cessation. Male rats received saline, 6 mg/kg/day or 12 mg/kg/day nicotine delivered subcutaneously by osmotic minipumps. The pumps delivered their contents during a 10-day period of implantation, after which time they were explanted. Animals were tested for startle reflex amplitudes using two levels of white noise bursts prior to pump implantation, on days 1 and 7 of nicotine or saline administration, and on several days following drug cessation. Nicotine produced a dose-dependent increase in startle amplitude during the period of administration that decreased during cessation. Results are interpreted in terms of nicotine's actions to enhance attentional processes. PMID- 1876670 TI - An animal model of anhedonia: attenuation of sucrose consumption and place preference conditioning by chronic unpredictable mild stress. AB - Chronic exposure to very mild unpredictable stress has previously been found to depress the consumption of, and preference for, highly palatable sweet solutions. The present study used the place conditioning procedure to investigate whether these effects result from a decreased sensitivity to reward. Rats were subjected to chronic mild unpredictable stress for a total of 4 weeks. During weeks 3 and 4, they received four training trials, in which rewards were presented in a distinctive environment, and four further non-rewarded trials in a different environment. The rewards used in different experiments were food pellets, dilute (0.7%) and concentrated (34%) sucrose solutions, and dl-amphetamine sulphate (0.5 and 1.0 mg/kg). In all experiments, non-stressed animals showed an increase in preference for the environment associated with reward; in stressed animals, these effects were abolished or greatly attenuated. Chronic unpredictable mild stress, which may be comparable in intensity to the difficulties people encounter in their daily lives, appears to cause a generalized decrease in sensitivity to rewards. PMID- 1876671 TI - Naloxone blockade of amphetamine place preference conditioning. AB - Amphetamine and naloxone were examined in place conditioning, in order to study possible interactions between endogenous opioids and catecholamines in reinforcement. After initial preferences were determined, animals were conditioned with amphetamine alone (1.0 mg/kg SC), naloxone alone (0.02, 0.2 or 2.0 mg/kg SC) or combinations of amphetamine plus naloxone. A reliable, long lasting preference for the compartment associated with amphetamine was observed, reflecting the reinforcing properties of this drug. No preference or aversion was observed in animals that received saline in both compartments. Naloxone (0.02, 0.2 and 2.0 mg/kg) produced a dose-dependent place aversion; while the lowest dose had effects similar to saline, the higher doses produced significant place aversions. Naloxone, at all three doses examined, prevented the ability of amphetamine to produce a place preference. Thus, the lowest dose of naloxone, having no effects alone in place conditioning was still able to block the reinforcing effects of amphetamine. These results suggest that the reinforcing effects of amphetamine are dependent on activation of opiate receptors, and provide further evidence that interactions between endogenous opioids and catecholamines may be important in reinforcement. PMID- 1876672 TI - Enhanced development of morphine tolerance in rats treated with 2-deoxy-D galactose. AB - Rats treated subcutaneously for 6 days with morphine developed a weak tolerance which was characterized by a decrease in the analgesic action of the opioid. Under those experimental conditions a simultaneous intracerebroventricular application of 2-deoxy-D-galactose enhanced development of morphine tolerance, while other deoxy-sugars like 2-deoxy-D-glucose and 6-deoxy-D-galactose were ineffective. In contrast, no influence of 2-deoxy-D-galactose on a more enhanced morphine tolerance after a 11-day pretreatment with morphine was found. The results are discussed in the light of a rather specific interference of 2-deoxy-D galactose with neuronal glycoprotein processing and related cellular mechanism underlying adaptive processes involved in the development of morphine tolerance. PMID- 1876673 TI - Audiogenic seizure susceptibility: inhibitory effect of glucose injection is counteracted by prior glucose. AB - Audiogenic seizure susceptibility was examined in SJL/J mice injected with glucose 15-30 min before priming and/or subsequent tests. The obtained results confirm previous reports that glucose will inhibit seizure activity if given shortly before a test. In addition, it was found that glucose give 2-4 days previously would counteract the inhibitory effect of glucose injected shortly before testing. PMID- 1876674 TI - Society for Psychophysiological Research, 31st annual meeting. October 9-13, 1991, Chicago, Illinois. Abstracts. PMID- 1876675 TI - The use of biosensors in pacemaker technology: experience with a ventricular rate responsive pacemaker. AB - Ten elderly patients each had a ventricular rate responsive pulse generator (Activitrax) placed in them to help correct severe conduction abnormalities; none had suspected ischemic heart disease. The pulse generator was programmed to a maximal pacing rate of 125 ppm, a medium activity threshold, and a rate response of 6. Six weeks after implantation of the pulse generator, the patients were evaluated before exercising and again when the pacing rate reached 125 ppm. The evaluation protocol included an M-mode echocardiogram from which the following measurements were taken: the left ventricular end-diastolic volume (EDV), the end systolic volume (ESV), the ejection fraction (EF), and the peak systolic pressure/end-systolic volume (PSP/ESV). The numerical values were recorded, calculated, and compared statically with the following results: the EDV increased from 91 +/- 10 to 125 +/- 20 cc (p less than .05); the ESV decreased from 64 +/- 10 to 24 +/- 6 cc (p less than .005); the EF increased from 41 +/- 5 to 61 +/- 10% (p less than .05); and the PSP/ESV ratio increased from 1.70 +/- 1 to 4.10 +/ 2 mm Hg/cc (p = 10). Also, during the maximal pacing rate, the septum of all patients showed paradoxical septal motion. All patients in our study have been asymptomatic and have shown an increase in their exercise capacity. We conclude that during exercise the left ventricular function ins influenced more by heart rate than by AV synchrony, as indicated by an elevated EDV in most patients. PMID- 1876676 TI - Bacterial infections in a hematology and oncology inpatient unit. Changing spectrum of bacteremias. AB - The incidence of infection is increased in patients with cancer and certain hematologic disorders. We retrospectively reviewed all the patients evaluated for infection in our Hematology-Oncology unit during a six month period. The purpose of this study was to identify the most common organisms causing infection, evaluate the usefulness of tests performed as well as to determine the outcome and complications of therapy. Contrary to earlier experience the most common organisms causing bacteremia were gram-positive. Despite this finding, gram negative organisms remained important pathogens specially of the respiratory and urine tract judging by their predominance in urine and sputum cultures. Of the commonly ordered tests, the chest X-ray was the most frequently positive test for infection and the complication rate of antibiotic therapy was 15%. We conclude that in addition to the traditional antibiotics effective against gram-negative organisms, institution of antibiotics effective against gram-positive organisms including Staphylococcus epidermides, should be considered early in the management of these patients. PMID- 1876677 TI - New concepts in the field of vascular disorders of the skin. PMID- 1876678 TI - Health conditions among elderly Puerto Ricans: gender differences. AB - The health conditions of 466 free-living elderly Puerto Ricans were surveyed islandwide between September 1984 and September 1985. The questions pertaining to this topic are made up of 17 items: seven questions about background information and a list of ten of the most frequently reported health conditions among the elderly. It is part of a larger study of the socio-demographic characteristics of this population, comprised of 173 questions. The statistical tests of significance utilized were those of Kendall's Tau B and Cramer's V. The structural variables of sex, age, and marital status were found to be the most statistically significant for the presence of health conditions at the time of the interview. The implications of this for the elderly, social and public policy planners, formal and informal care gives and the health care establishment are discussed. PMID- 1876679 TI - [Utilization of health services in Puerto Rico of persons with mental disorders]. AB - As part of a major study on the prevalence of mental disorders in Puerto Rico, this paper describes the mental health care utilization patterns of persons with a Diagnostic Interview Schedule (DIS) disorder within the last year. The main findings of this analysis show that a) there is a high rate of health service utilization, b) the public sector is the main provider of services c) persons with a DIS disorder use more the non psychiatric physician d) those with alcohol abuse and/or dependence tend to use more the services of general practitioners while schizophrenics, somatizers and those with cognitive impairment use more the services of mental health specialists. The use of other resources such as clergy or spiritualists do not substitute the use of health services. PMID- 1876680 TI - [Knowledge, practices and attitudes towards AIDS in young Puerto Ricans]. PMID- 1876681 TI - "Is leishmaniasis possible in Puerto Rico?". AB - In a survey encompassing eight different ecological regions, Lutzomyia cayennensis puertoricensis was found in five, and L. c. viequesensis in one of 24 sites. The search centered on arboreal microhabitats. These subspecies were the two phlebotomids reported 40 years before by Fairchild and co-workers. In the face of these findings the possibility of leishmaniasis being introduced from the Dominican Republic is discussed. It was concluded that conditions in Puerto Rico do not seem apt for the establishment of the disease. PMID- 1876682 TI - Lactic acid levels as a prognostic measure in acutely Ill patients. PMID- 1876683 TI - Striving for the sharpest image. PMID- 1876684 TI - Radiography of the ankle mortise. AB - Radiographers often use methods to position the ankle that produce inaccurate images of the ankle mortise. This article describes a technique using a 15 degree to 20 degree internal-oblique position of the leg and foot to demonstrate the ankle mortise radiographically. A textbook protocol also is included. PMID- 1876685 TI - Port film dosage in radiation therapy. AB - Portal verification has led many radiation therapy departments to implement policies of taking weekly port films for every patient. This has caused some to question the impact of port film dosage, once considered negligible. Using clinical data from 100 patients, this article examines the impact of port film dosage and offers suggestions for documentation and alternatives for decreasing dosages. PMID- 1876686 TI - Computer frame freezing of fluoroscopic images. AB - Simple but flexible frame freezing of fluoroscopic images can improve the utility of real-time x-ray imaging. A frame-freeze system based on a personal computer has been developed. The system is easily installed using standard hardware that is non-invasive of the fluoroscopic imaging chain. The frozen images can be used as a reference or for hard-copy documentation of real-time or videotaped procedures. PMID- 1876687 TI - Teaching strategies to foster critical thinking. AB - The teaching of critical thinking is a relatively new focus in higher education. Some argue that to advance as a profession radiologic technology must examine the role of critical thinking in the professional curriculum. Attitudes that impede critical thinking are presented as well as sample teaching methods designed to foster critical thinking. PMID- 1876688 TI - People make the difference. PMID- 1876689 TI - Educational levels, ethnic origin and age. PMID- 1876690 TI - Click on the video learning connection. PMID- 1876691 TI - Child abuse--mistaken diagnosis? PMID- 1876692 TI - [Low radiation doses: risks and benefits]. PMID- 1876693 TI - [Radiation risks. Results of the new evaluation]. AB - The dose revision for the atomic bomb survivors of Hiroshima and Nagasaki and the evaluation of cancer mortality, based on data up to 1985, resulted in new estimates of radiation risks that are substantially larger than the earlier estimates. The new results and reasons for the changes are discussed. The risk estimates are related to the current discussion on dose limits in radiation protection and to the attempts to reduce doses in X-ray diagnostics. PMID- 1876694 TI - [A new radiation protection dose limit for occupationally exposed personnel in the Federal Republic of Germany]. AB - In the Federal Republic of Germany, as in most other countries, the dose limit is 50 mSv per year for occupationally exposed persons, as recommended by the International Commission on Radiological Protection (ICRP). A reduction in the annual dose limit was recently considered in connection with a discussion of a higher estimation of radiation risk. In the recent amendment of the German Radiological Protection Ordinance, however, the dose limit of 50 mSv per year was retained and additionally a new occupational lifetime dose limit of 400 mSv was introduced. The possible consequences of the 400 mSv dose limit will be discussed on the basis of the previous results of dose monitoring in the Federal Republic of Germany. PMID- 1876695 TI - [Intra-arterial fibrinolysis in central artery occlusion]. AB - Central retinal artery occlusion is known to have a poor natural outcome, and also conventional therapeutic procedures e.g. paracentesis, hemodilution or local massage show unfavorable results. As in intraarterial fibrinolytic therapy in cerebral vessels, we also applied this method to the territory of the ophthalmic artery in 6 patients with occlusion of the central retinal artery. The fibrinolysis was done with a microcatheter superselectively, placed in the proximal part of the ophthalmic artery. The amount of urokinase varied from 200,000 to 900,000 IU, diluted in saline solution. In 5 patients, fluorescein angiography was carried out before and after fibrinolytic therapy, confirming the significant improvement of retinal and choroidal perfusion seen on the arterial ophthalmic angiogram. All patients showed an improvement of visual function after therapy, two patients even had a complete recovery of visual acuity. PMID- 1876696 TI - [Intracranial giant aneurysm due to the effects of radiation]. AB - Two cases of intracranial giant aneurysms of the carotid artery are presented, probably caused by radiation damage. Both patients had been treated for hypophyseal adenoma by transfrontal implantation of yttrium seeds (35 and 45 mCi). Preoperative carotid angiographies had shown no vascular abnormalities; the aneurysms were revealed 8 and 11 years after these examinations. No identical cases could be found in the literature. Further etiological hypotheses are discussed. PMID- 1876697 TI - [Spontaneous healing of a carotid-cavernous sinus fistula]. AB - After a fall, a 67-year-old patient was admitted to our hospital. The unique clinical sign was an exophthalmus, which led to the diagnosis of carotid cavernous sinus fistula. During his stay in our clinic the fistula was verified by CT and angiography. Transfemoral embolization was planned, but the fistula closed spontaneously prior to the intervention. PMID- 1876698 TI - Congenital A-V fistula of the breast. AB - A case of congenital A-V fistula in the breast of a young woman is presented. The chief complaint was murmur when lying down, especially in the prone position, a palpable lump and the presence of varicose-like veins in the breast. Arteriography revealed an A-V fistula in the left breast. The arterial supply originated from the ipsilateral internal mammary vein and superior thoracic artery and drainage was towards the axillary vein and, to a minor degree, towards the internal mammary vein. The lesion was corrected surgically. Six months later there was no evidence of recurrence. PMID- 1876699 TI - Postprandial gastro-oesophageal reflux demonstrated by radiology. AB - An investigation to detect food-stimulated gastro-oesophageal (GE) reflux was carried out in 54 consecutive fasting patients, 35 of whom experienced reflux while 19 did not. All patients then received a standard meal (566 kcal), and the investigation was repeated 1 h later. Out of the 35 with GE reflux in the fasting state, 33 also had GE reflux in the postprandial state, and 17 of the 19 patients with no GE reflux while fasting also had none in the postprandial state. It is concluded that the radiological method can identify most patients in whom food stimulated GE reflux could be of clinical significance. PMID- 1876700 TI - [Multiple para-aortal accessory spleens. Differential diagnosis from retroperitoneal lymphoma]. AB - We report a case of multiple paraaortic accessory spleens in the retroperitoneal space. CT guided large-bore biopsy confirmed the diagnosis and excluded malignant involvement of retroperitoneal lymph nodes. PMID- 1876701 TI - [History of the German-Japanese Radiological Affiliation]. PMID- 1876702 TI - [An unusual cardiac configuration. Heterotopic heart transplantation in endomyocardial fibrosis]. PMID- 1876703 TI - [Acute pancreatitis?]. PMID- 1876704 TI - Nurse negligent in mixing twins: Res Ipsa Loquitur. PMID- 1876705 TI - Recovery room nurse fails to monitor patient. Case in point: Eyoma v. Falco (589 A. 2d 653--NJ 1991). PMID- 1876706 TI - Legal case briefs for nurses. OR.: did nurse fail to call ambulance?; "Hearsay evidence"; GA.: agency seeks injunction vs. former employee: "trade secret". PMID- 1876707 TI - Sexual relationship with patient: license revocation. Case in point: Heinecke v. Dept. of Commerce (810 P, 2d 459--UT 1991). PMID- 1876708 TI - Drug receptors and control of the cardiovascular system: recent advances. PMID- 1876709 TI - Molecular modeling and quantitative structure-activity analysis of antibacterial sulfanilamides and sulfones. PMID- 1876710 TI - Chemistry and pharmacology of cannabis. PMID- 1876711 TI - Pharmacology of synthetic organic selenium compounds. PMID- 1876712 TI - [Idea and reality of teaching analysis. A plea for reforms (I)]. PMID- 1876714 TI - [Religious roots of antisemitism]. AB - In agreement with Freud, the author characterizes the unconscious structure of ecclesiastic and of contemporary racist anti-Semitism as paranoid projections of unconscious guilt feelings and of profound narcissistic injury. Chasseguet Smirgel's thesis concerning the perverse character of anti-Semitism and Ostow's attempt to relate anti-Semitism to apocalyptic ideas are discussed as well. PMID- 1876713 TI - [3 letters by Anna Freud to Eva Rosenfeld]. PMID- 1876715 TI - Case #4. Irritation fibroma. PMID- 1876716 TI - Health link. We owe it to the growing number of women afflicted with bulimia to be informed, aware and to care. PMID- 1876717 TI - Second time around. PMID- 1876718 TI - Make time for treatment. There needs to be a clear distinction between a recall, root planing and routine appointment. PMID- 1876719 TI - Joint risk from multiple compound exposure. PMID- 1876720 TI - The dependence of the risk of research reactors from their operating schedule--a case study. AB - The dependence of the radiological consequences of the "Demokritos" research reactor on the operating schedule of the reactor is assessed in this paper. The 5 MW reactor is located within the limits of Athens city, a large population center with over 3 million inhabitants. The consequences examined would be due to the occurrence of a postulated accident, a 20% core melt loss of coolant accident, that is also considered as the design basis accident of the reactor. Three operating schedules are taken into account: (a) a continuous operation schedule; (b) a 16 hr/day, 5 days/week schedule; and (c) the present 8 hr/day, 5 days/week operating schedule. The assessment of the source term emerges from a conservative estimation of fission product releases to the reactor operating floor, and further under the conservative assumptions of no filter mitigation, and a ground release to the environment. The results of the analysis indicate that there is a direct relation between consequences and duration of operation, the former becoming appreciable as the continuous operation limit is approached. In all cases examined, the thyroid dose and the latent thyroid health effects would be the limiting consequences. PMID- 1876721 TI - The Seveso Directive: an Italian pilot study in enabling communication. AB - In 1982 the Council of the European Communities issued a Directive on the Major Accident Hazards of Certain Industrial Activities, commonly known as the Seveso Directive. Besides other requirements, the Directive specifies that members of the public liable to be affected by a major accident from certain industrial activities must be informed of safety measures and how they should behave in the event of an accident. The Directive was subsequently amended in an extensive way. Upon the transposition of the Seveso Directive and its amendments into national legislations, the 12 European Member States are faced with the task of "appropriately and effectively" informing the public about major accident hazards. Delays are observed throughout the community, both in transposing the Directives and implementing public information. A pilot study on "Risk Information Needs" was commissioned and carried out at two Seveso sites in Italy in order to begin to resolve some of the problems involved in the provision of public information and to suggest appropriate guidelines. One hundred subjects answered an experimental protocol designed to assess their "information needs." This article presents the theoretical background, the pragmatic aims, and the design of the study. It also summarizes its most relevant findings and suggests some recommendations for the provision of information to the public. PMID- 1876722 TI - Risk prevention and policy-making in automatic systems. AB - Accidents with automatic production systems are reported to be on the order of one in a hundred or thousand robot-years, while fatal accidents are found to occur one or two orders of magnitude less frequently. Traditions in occupational safety tend to seek for safety targets in terms of zero severe accidents for automatic systems. Decision-making requires a risk assessment balancing potential risk reduction measures and costs within the cultural environment of a production company. This paper presents a simplified procedure which acts as a decision tool. The procedure is based on a risk concept approaching prevention both in a deterministic and in a probabilistic manner. Eight accident scenarios are shown to represent the potential accident processes involving robot interactions with people. Seven prevention policies are shown to cover the accident scenarios in principle. An additional probabilistic approach may indicate which extra safety measures can be taken against what risk reduction and additional costs. The risk evaluation process aims at achieving a quantitative acceptable risk level. For that purpose, three risk evaluation methods are discussed with respect to reaching broad consensus on the safety targets. PMID- 1876723 TI - Applications of probabilistic risk assessments: the selection of appropriate tools. AB - Probabilistic risk assessment (PRA) is an important methodology for assessing the risks of complex technologies. This paper discusses the strengths and weaknesses of PRA. Its application is explored in three different settings: adversarial policy processes, regulatory/licensing procedures, and plant safety audits. It is concluded that PRA is a valuable tool for auditing safety precautions of existing or planned technologies, especially when it is carried out as an interactive process involving designers and plant personnel who are familiar with actual, everyday operations. PRA has not proven to be as well-suited in providing absolute risk estimates in public-policy debates concerning the acceptability of a technology, or for the licensing and regulatory procedures. The reasons for this are discussed. PMID- 1876724 TI - More large accidents through complexity? AB - Many would tend to characterize modern society as steeped in complexity. This complexity is seen by a number of professional people to imply risk-taking--or risk-making--on a high level. "A single mistake may give consequences of quite different proportions from earlier times," as one critic puts it. This hypothesis of increasing risks on a high level--of worst things getting worse--has been tested on fires in Sweden. Fire has always been a powerfully upsetting agent to the social fabric. Today industrial fires dominate the picture economically. The cost of industrial fires is about three times the cost of residential fires in Sweden. It is of interest to note that the damage cost of the worst fires (as measured in insurance payments) does not form an increasing part of overall fire damage costs, as one would expect from the above hypothesis. Whether the hypothesis holds with regard to indirect costs due to production stand-still is more uncertain. We can conclude that the potential of complexity to create large abnormal occurrences may have been somewhat prematurely announced--at least with regard to fires in Sweden. PMID- 1876725 TI - Public perception of the risks of floods: implications for communication. AB - Floods in the U.S. kill an average of 162 people each year and cause $3.4 billion in property damage. Flood control programs have been successful in lowering, but not eliminating, the risks to lives and property. Since the late 1960s, the federal government has emphasized flood insurance as a primary tool for improving location and flood-proofing decisions, as well as for reimbursing flood losses. Since only 12.7% of houses in flood plain areas are covered by flood insurance, the program has been ineffective. We interviewed people living in three communities that had recently been flooded. Most people had little knowledge of the cause of floods or what could be done to prevent damage. People who work and who are better educated know more and are more likely to have flood insurance. Current government publications about flood risks are not likely to be understood by those at risk. There is little effective communication about the nature and magnitude of the risks and what individuals can do to protect their lives and property and lower their financial risks. The risk management program should both emphasize communication and enforcement of the current law requiring people at risk who hold federally funded loans to be insured. PMID- 1876726 TI - Fishing a superfund site: dissonance and risk perception of environmental hazards by fishermen in Puerto Rico. AB - Risk perception studies show that individuals tend to underestimate significant risks, overestimate negligible ones, and distrust authorities. They also rely on a variety of strategies or heuristics to reach decisions regarding their risk taking behavior. We report on a survey of fishermen and crabbers engaged in recreational and substance fishing in a Puerto Rican estuary (near Humacao), which has been declared a "Superfund site" because of suspected contamination by mercury, and at ecologically similar control sites. Nearly everyone interviewed at the Humacao site was aware of the mercury contamination, but either denied its importance, believed the contamination was restricted to a distant part of the estuary, or assumed that the estuary would be closed by the authorities if the threat was real. All site-users consumed the fish and crabs they caught. At Humacao, the average catch was 7 fish per fishermen (mostly tilapia, Tilapia mossambica, and tarpon, Megalops atlantica) and 13 crabs per crabber (all blue crabs, Callinectes sapidus). On average, the site-users returned to the lagoons about 3-4 times per month. At control sites, fewer fish were eaten. The worst case consumption of tarpon, a species which concentrated mercury at Eastern Puerto Rico, provided an exposure exceeding the EPA reference dose, whereas consumption of one tarpon per week did not entail excess exposure. Fortunately, few individuals caught tarpon exclusively. Unlike counterparts in the northeastern United States, they trusted authorities and indicated that they would have heeded warnings of mercury contamination posted where they fished. PMID- 1876727 TI - Predicting EPA's forthcoming CO standards in light of new clinical evidence. AB - For the past several years, the EPA has been monitoring clinical studies on the adverse health effects of heart patients' exposure to carbon monoxide. This paper examines the impact of three such studies (including the multi-center CO study organized by the Health Effects Institute) on the forthcoming EPA standards for carbon monoxide. Eleven peer-nominated specialists with expertise in environmental science and public policy were interviewed according to a specific protocol. Overall, the experts felt that the HEI study would receive greater weight than the other two studies in the regulatory process for a variety of technical reasons. Weighting each expert opinion equally, we conclude that there is about a 0.69 probability that the CO standards will be retained at their present levels, a 0.28 probability that the standards will be tightened, and a 0.03 probability that the standards will be relaxed. When asked to imagine that the HEI data were never collected and then asked to reassess their probability judgments, the mean probability judgment that the standards will be relaxed rose to 0.11, while the mean probability judgment that the standards will be tightened fell to 0.20. A modest degree of variability in expert opinion is reported in the paper. While the HEI study may receive relatively great weight in the regulatory process, it increases only slightly the probability that EPA's CO standards will be changed. PMID- 1876728 TI - A note on the influence of rail defects on the risk associated with shipping hazardous materials by rail. AB - Existing approaches to routing hazardous material shipments by rail recognize that track condition is an important influence, but have not included it in the risk assessment and routing models. This note explores the influence of track condition based on predictions of internal defects in the rail. The method developed predicts the expected frequency of accidents and subsequent consequences in terms of the expected number of fatalities accounting for one aspect of track condition-internal defects. It is intended to indicate the magnitude and impact of track condition. The formulation integrates models of consequences and the risk of a hazardous spill found in the literature with the frequency of accidents as a function of the number of defects. The number of defects may be based on observations or predicted as a function of the cumulative traffic. The models are used to calculate the expected number of fatalities per year for a particular route. Application of the methodology to a hypothetical route shows that the risk associated with the transportation of hazardous material shipments varies significantly with the expected number of defects in the track. Therefore, risk not only varies from route to route but over time for any section of track as the condition deteriorates. PMID- 1876730 TI - A review of FaultrEASE version 1.0. AB - Many systems analysts will be surprised to encounter a program which is billed as a fault-tree development program "perform[ing] logical mathematical operations," but which does not perform Boolean reduction. The rather careful wording quoted in the introduction to this review can, in retrospect, be taken to refer to the fact that gates are quantified using formulas from the calculus of probabilities, and not to claim that Boolean reduction is performed. Since this program does not perform Boolean reduction, its use is limited to essentially graphical applications of the type illustrated in Fig. 1. For this limited application, the program has some features which make it attractive; it is easy to develop and print a passable drawing of a fault tree, and it is easy to do "what-if" analyses (looking at the effects of changing connections or statistics). However, for fault-tree analyses of even moderate complexity, a Boolean processor is necessary (a large fault tree for a real problem in which no events are repeated is arguably a pathological case). Many such algorithms exist on DOS machines, and most of them run within (and are limited to) the usual 640k memory limitation. To be fair, it has to be noted that some commercial algorithms of this type cost far, far more than FaultrEASE (their costs are measured in thousands of dollars rather than hundreds).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876729 TI - Parametric distributions for soil ingestion by children. AB - This note presents parameterized distributions of estimates of the amount of soil ingested by children based on data collected by Binder et al. (1986). Following discussions with Dr. Binder, we modified the Binder study data by using the actual stool weights instead of the 15 g value used in the original study. After testing the data for lognormality, we generated parameterized distributions for use in risk assessment uncertainty analyses such as Monte Carlo simulations. PMID- 1876731 TI - [History of the introduction of ether anesthesia in Spain. A new contribution to its study]. AB - Ether anesthesia was introduced in Spain on January 13, 1847. Dr. Diego de Argumosa y Obregon, from Madrid, was the first Spanish surgeon who operated with the help of sulphuric ether. Almost at the same time, by the end of January, the dentist Oliverio Machechan administered ether to 2 patients in whom he performed dental operations. Subsequently, ether was used in several parts of Spain: Barcelona, Pamplona, Motril, and by several Madrid surgeons through February and March. In Santiago de Compostela ether was also introduced very soon, and, on the basis of the data from the studies of Dr. Jose Gonzalez Olivares (the surgeons who first tried it in that town), most authors dealing with this issue state that it was probably in Santiago de Compostela where these experiments were carried out simultaneously with those by Argumosa in Madrid or even before. We have in some occasions defended that thesis; however, we were not satisfied with it and we decided to reinvestigate the facts. We had access to other sources and we concluded that anesthetics were really used a very early phase in Santiago de Compostela, but in the case of ether it was later than Argumosa and Oliverio Machechan used it in Madrid and Mendoza in Barcelona. In the present article we analyze these facts in detail, with emphasis on those that we consider historically relevant and that had not been previously dealt with by any other author addressing these issues. PMID- 1876733 TI - [Anesthetic management of a hydatid cyst adhering to the inferior vena cava]. AB - A patient with a hepatic hydatid cyst with fistula formation to inferior vena cava is reported. To carry out the resection, the cyst was isolated from systemic circulation by means of cardiopulmonary bypass. Inferior vena cava was cannulated through the right atrium until the implantation area of the cyst (above the hepatic veins) was surpassed. Bypass was carried out in 25 minutes by means of cannulation of the ascending aorta, without clamping the aorta, myocardial protection or hypothermia. Postoperative analgesia was achieved with a lumbar epidural catheter. Measures to prevent anaphylactic shock are recommended, an anesthetic technique based on the prevention of hypersensitivity reactions and a careful surgical technique to prevent hydatid dissemination. PMID- 1876732 TI - [Anesthetic approach in 2 patients with pulmonary lymphangiomyomatosis]. AB - Pulmonary lymphangiomyomatosis (PLM) is an idiopathic disease of females in fertile age. It results in respiratory failure characterized by obliteration of the small airways, emphysema, formation of bullae, hemoptysis, pneumothorax, pulmonary fibrosis, severe hypoxemia and reduced carbon monoxide diffusion capacity. The major lymphatic ducts are also involved, resulting in chylous pleural effusion and ascites. Pulmonary abnormalities improve objectively and subjectively after surgical therapy, which consists in bilateral oophorectomy. Its evolution results in death in no more than 10 years. We report the anesthetic approach to 2 patients with PLM. Patient 1 was a female who had already been diagnosed of PLM and had received medical and surgical therapy, requiring reoperation for the resection of cystic intestinal masses and abdominal eventration. Patient 2 had been scheduled for bilateral oophorectomy after a diagnosis of PLM. We discuss the clinical condition of both patients, the course of the disease, the previous treatments and the anesthetic technique in each case. PMID- 1876734 TI - [A rare complication of endotracheal intubation: posterior luxation of the left arytenoid cartilage]. AB - The luxation of the arytenoid cartilage is a very uncommon complication of endotracheal intubation. Symptoms usually are aphonia, dysphonia, pain or discomfort in the throat, odynophagia and laryngeal stridor. It may be due to several factors: the pressure of the convex aspect of the tube on the arytenoid, traumatic or prolonged intubations, reintubations within a short period, or some systemic diseases. We report a case of posterior luxation of the left arytenoid in a patient who had been anesthetized for the radical cure of a left inguinal hernia. The clinical features developed when he recovered from anesthesia, with aphonia and discomfort in the throat. The diagnosis was made by indirect laryngoscopy. Treatment with nonsteroidal antiinflammatory agents was instituted. Aphonia disappeared after 2 weeks and dysphonia persisted. The patient became asymptomatic with corticosteroids on the fourth week after operation. Early diagnosis under laryngoscopic vision is recommended, with adequate therapy to prevent fibrosis of the cricoarytenoid joint with permanent sequelae. PMID- 1876735 TI - [Diclofenac reduces the sedative and hypnotic dosage of midazolam]. PMID- 1876737 TI - [Flumazenil in the treatment of floppy baby syndrome]. PMID- 1876736 TI - [Epidural morphine and naltrexone: withdrawal syndrome]. PMID- 1876738 TI - [Allergic reactions to local anesthetics]. PMID- 1876739 TI - [Ether anesthesia by the rectal route]. PMID- 1876740 TI - [Ether by the rectal route for the treatment of cholera]. PMID- 1876741 TI - [Committee on ethics and clinical investigation]. PMID- 1876743 TI - [Epidural perfusion with fentanyl in the treatment of postoperative pain]. AB - In 40 patients with high abdominal surgery the analgesia achieved with continuous epidural phentanyl infusion was evaluated. Treatment was started when the patients had pain, with the injection of 150 micrograms of phentanyl in 18 ml of saline and going on with the infusion. The patients were divided in 4 groups. Each received a different infusion dose. The variables pain, alertness, pO2, pCO2 and hemodynamic status at the beginning of infusion and after 6, 18 and 24 hours were evaluated. All patients had an adequate postoperative analgesia. In the statistical analysis the only significant difference was an increase in pCO2 after 24 h in the patients who received the highest doses. The incidence of nausea and vomiting was 10%, with 13.04% of urinary retention Clinical respiratory depression was not observed. We think that administration of 150 micrograms of epidural phentanyl followed by a continuous epidural infusion of the drug (0.5 microgram/kg/hour in 5 ml of saline) is an adequate technique of postoperative analgesia. PMID- 1876742 TI - [Comparative study of peridural anesthesia with bupivacaine alone and combined with fentanyl during vaginal delivery]. AB - Two groups of primiparous women with single fetus in cephalic presentation were prospectively randomized at the end of pregnancy to receive epidural analgesia with 0.25% bupivacaine, either single (n = 102) or associated with 0.05 mg of phentanyl (n = 102). Phentanyl significantly reduces the period of development of analgesia and increases the interdose period. The quality of analgesia is significantly better when fentanyl is associated with bupivacaine. The evolution of delivery (dilatation and expulsion) and the perinatal results (cord pH and vitality of the newborn as assessed by the Apgar test) were similar in both groups. We conclude that the association of phentanyl with bupivacaine has advantages for epidural analgesia during delivery, as the quality of analgesia is improved, its duration is prolonged and there are no adverse effects on the evolution of delivery or on the newborn. PMID- 1876745 TI - [Changes in total and differential leukocyte counts during heart surgery with extracorporeal circulation]. AB - The changes in leukocyte overall and differential counts during anesthesia and surgery were evaluated in 24 patients scheduled for cardiac surgery with cardiopulmonary bypass. All the end of cardiopulmonary bypass a marked and sustained leukocytosis was found (10.2 and 11.1 x 10(9).l-1), which was significantly different from baseline values (6.7 x 10(9).l-1), the values previous to cardiopulmonary bypass (6.2 and 6.4 x 10(9).l-1, and the values 30 minutes after it (5.3 x 10(9).l-1). In the differential count there were significant increases in neutrophils, associated with band and immature forms, corresponding with significant reductions in lymphocytes. There was no significant association of leukocyte variability during and after cardiopulmonary bypass and the perfusion time, the type of oxygenator or the need for intraoperative transfusion. All the reported changes tended to become normal during the first postoperative days. PMID- 1876746 TI - [Platelet changes during heart surgery with extracorporeal circulation]. AB - The changes in the number of platelets during anesthesia and operation were evaluated in 24 patients (8 females and 16 males) scheduled for cardiac surgery with cardiopulmonary bypass. There was a significant (p less than 0.05) thrombopenia at the beginning of perfusion, which persisted 60 minutes after the end of cardiopulmonary bypass. There were no significant differences when these changes were evaluated depending on the type of oxygenator, the need for transfusion or the duration of cardiopulmonary bypass. There was a reduction in the platelet count at the beginning of the bypass (207 to 124 x 10(9).1(-1), when blood contacts with the synthetic surfaces of the circuits and the oxygenator, al though-the most marked reduction was found at the end of bypass (95.9 x 10(9).1 1), coinciding with protamine administration. The function and number of platelets tended to become normal in the first hours of the postoperative period. PMID- 1876744 TI - [Addition of fentanyl to mepivacaine in axillary brachial plexus block. Effects on the anesthetic and postoperative analgesic quality]. AB - The possible potentiating effect of phentanyl on mepivacaine in brachial plexus blockade was evaluated, both for operative anesthesia and postoperative analgesia. Sixty ASA I patients, scheduled for upper limb surgery, were selected and distributed in 3 groups: 1) Mepivacaine 1% 40 ml (control group); 2) Mepivacaine 1% 40 ml + phentanyl 100 micrograms; 3) Mepivacaine 1% 40 ml + subcutaneous phentanyl 100 micrograms. The latency time and the quality of anesthesia were evaluated. The duration of analgesia was evaluated on the basis of the time from the administration of the first analgesic. There were no significant differences between the 3 groups in the latency times of the development of blockade nor in the quality of surgical anesthesia. Also, there were no significant differences in the duration of postoperative analgesia (307, 316 and 326 minutes, respectively, in each group). It was concluded that the addition of phentanyl 100 micrograms to the local anesthetic in the axillary blockade of the brachial plexus does not change the anesthetic characteristics nor the time of postoperative analgesia. PMID- 1876747 TI - Effects of CD-349, a dihydropyridine derivative, on contraction induced by vasoactive agents in canine basilar artery after subarachnoid hemorrhage. AB - We investigated the effects of CD-349, a dihydropyridine derivative, on contraction induced by vasoactive agents in canine basilar artery after subarachnoid hemorrhage (SAH). Ca(2+)-induced contraction of basilar arterial strips preincubated with serotonin (5-HT, 3x10(-6)M) was potentiated in strips from SAH. However, Ca(2+)-induced contraction of arterial strips which were depolarized with isotonic K+ (64mM) was attenuated in strips from SAH. These Ca(2+)-induced contractions of the basilar arteries preincubated with 5-HT and K+ from both control and SAH dogs were significantly inhibited by CD-349 and nicardipine, both dihydropyridine derivatives. 5-HT contracted the basilar arterial strips in a concentration-dependent manner; however, the maximal contraction of the basilar arterial strips to 5-HT was enhanced in SAH. Endothelium-dependent relaxation in response to substance-P was attenuated in SAH when compared to that in control dogs. Early treatment with CD-349 (1 or 2mg/kg/day, i.m.) for 1 week reversed not only the enhanced contraction of the basilar artery in response to 5-HT but also the impairment of endothelium dependent relaxation in response to substance-P in SAH. It is expected that CD 349 may be a useful agent for the treatment of cerebrovascular diseases such as SAH. PMID- 1876748 TI - Influence of a pre-existing phospholipidosis on the accumulation of amiodarone and desethylamiodarone in rat alveolar macrophages. AB - Amiodarone is an antiarrhythmic drug that concentrates in the lungs and can cause pulmonary damage in humans. The purpose of the present study was to examine the influence of a pre-existing lung pathology on the pulmonary accumulation of amiodarone and its primary metabolite, desethylamiodarone. To study this problem, male Fischer 344 rats were administered chlorphentermine to induce a phospholipidosis in the alveolar macrophages of the lungs. The accumulation of amiodarone and desethylamiodarone in phospholipidotic alveolar macrophages was measured following 5 weeks of amiodarone administration. When calculated on a per cell basis, the levels of both drugs were increased over 10-fold in phospholipid laden macrophages compared to cells from control rats in which a phospholipidosis was not present. When phospholipidotic macrophages were exposed to amiodarone and desethylamiodarone in vitro, both drugs were accumulated to a higher level than occurred in cells from control rats. The results of this study demonstrate that the presence of a pre-existing phospholipidosis results in an enhanced accumulation of amiodarone and desethylamiodarone in rat alveolar macrophages. PMID- 1876749 TI - Enzymatic hydrolysis of indometacin farnesil, a prodrug of indomethacin, by carboxylesterase in cultured synovial cells. AB - The hydrolysis of indometacin farnesil (IMF) in the synovial cells of rat and human and the subcellular fractions of rat liver were investigated in relation to the inhibition of prostaglandin E2 (PGE2) production in the synovial cells. The inhibition of PGE2 production in cultured human synovial cells by anti inflammatory drugs was potent in the order of IND, IMF and acetyl salicylic acid. However, when the cells were pretreated with IMF, the inhibitory activity of IMF was retained even after the compound was washed out from the medium. No duration of the inhibition was seen in the pretreatment of the cells with IND or acetyl salicylic acid. These results suggest that IMF incorporated into the synovial cells was hydrolyzed gradually to IND. In fact, IMF was taken up by rat synovial cells in culture and considerable amount of IND, which increased with culture period, was found out in the cells. Furthermore, the IMF hydrolase activity was found in microsomal and lysosomal fractions of rat liver, and the hydrolase was identified as carboxylesterase by using bis-(p-nitrophenyl) phosphate, a specific inhibitor of carboxylesterase. PMID- 1876751 TI - Cyclosporin A blood levels are not influenced by dietary alterations in lipids. AB - The bioavailability of an oral dose of cyclosporin A (CSA) is variable. CSA is highly lipid soluble with approximately 40% of the CSA in the intravascular compartment bound to lipoproteins. This study was undertaken to determine what effect acute alterations in plasma lipids following a high fat meal would have on CSA whole blood levels 12 to 14 hours after the last dose. Fifteen renal transplant patients with stable renal function and on CSA therapy alone for a minimum of three months were investigated. Anthropometric data was recorded and baseline blood samples were drawn for CSA, liver function, renal function, vitamins A and E. triglycerides, cholesterol and lipoproteins following an overnight fast. The subjects then received a high fat (72.8% of caloric value) or a low fat (12% of caloric value) meal and post-prandial samples were drawn at two and four hours. The correlation between CSA levels (r = 0.72) taken on the two study days (one week apart) was less than expected despite no change in dosage. Cholesterol levels remained unchanged but triglyceride levels rose following the high fat meal. CSA levels did not correlate with the post-prandial changes in triglycerides, nor with any other parameter of lipid metabolism, lipid transport, or total body fat. This study demonstrated that CSA whole blood levels are not influenced by acute variations in lipids following a meal and therefore the time of sampling for a CSA trough level will not be influenced by the proximity to a recent meal. PMID- 1876752 TI - Effect of microcystin-LR (MCLR) on hepatic microsomal membrane fluidity. AB - Microcystin-LR (MCLR) is a potent cyclic heptapeptide hepatotoxin which appears to cause death due to hemorrhagic shock secondary to blood loss from the vasculature into the damaged liver. The molecular mechanism of toxicity is not known. Previous studies have demonstrated altered hepatic sulfhydryl status and enhanced lipid peroxidation following exposure of mice to MCLR. In the present study, mice were treated with 100 micrograms MCLR/kg and killed 10, 20 or 30 min post-treatment. Significant time-dependent decreases in hepatic microsomal membrane fluidity occurred. When microsomes from control animals were incubated in vitro with various concentrations of MCLR, no alterations in membrane fluidity were observed. The results suggest that MCLR-induced alterations in microsomal membrane fluidity involve an indirect and secondary effect rather than a direct interaction of the toxin with the membranes. PMID- 1876753 TI - Postnatal development of acetohexamide reductase activities in microsomes and cytosol of rat liver. AB - The postnatal development of acetohexamide reductase activities in liver microsomes and cytosol were examined in male rats. The developmental pattern of acetohexamide reductase activity in liver microsomes was distinguished from that in liver cytosol. Furthermore, acetohexamide reductase activity in liver microsomes was effectively suppressed by castration, but the activity in liver cytosol was not affected by castration. These results clearly indicate that enzymes with physiologically different roles can catalyze the metabolic reduction of acetohexamide in rat liver. PMID- 1876750 TI - Effect of vanadate on renal hypertrophy and sorbitol accumulation in streptozotocin induced diabetes in rats. AB - Vanadate has been previously shown to normalize blood glucose in streptozotocin induced diabetic (STZ-DM) rats. The effect of a previously studied dose of vanadate (0.8 mg/ml) in drinking water on blood glucose, renal hypertrophy, and whole kidney polyol accumulation was studied in STZ-DM rats. Rats with diabetes of 5 weeks duration had higher blood glucose, greater urinary output, higher kidney weight, lower body weight, and higher kidney to body weight ratios than controls. Whole kidney sorbitol concentrations were significantly increased in diabetes but myo-inositol levels were unchanged vs control animals. After four weeks of oral vanadate treatment, blood glucose, urine volume, and kidney weights were similar to control values. Kidney to body weight ratios fell below that of the STZ-DM animals, but because body weights remained decreased, the kidney to body weight ratios were not normalized. Renal sorbitol levels returned to control values and renal myo-inositol levels remained unchanged in STZ-DM and normal animals treated with vanadate. These results provide evidence that vanadate therapy may result in regression of the hypertrophy and polyol accumulation characteristic of diabetic nephropathy in STZ-DM rats. This effect is most likely due to normalization of blood glucose by the insulin-mimetic activity of vanadate treatment. PMID- 1876754 TI - Decrease in the specific forms of cytochrome P-450 in liver microsomes of a mutant strain of rat with hyperbilirubinuria. AB - Eisai-hyperbilirubinuria rats (EHBR) is a mutant originated from Sprague Dawley rats. The activities of UDP-glucuronyltransferase and drug metabolizing enzymes in EHBR were compared with those in Sprague Dawley rats as the control. The activity of aniline hydroxylase was significantly increased in liver microsomes of EHBR whereas the activity of ethylmorphine N-demethylase was found to be significantly decreased in EHBR as compared to control rats. In addition, the activity of testosterone 7 alpha-hydroxylase was increased in EHBR whereas the activity of testosterone 6 beta-hydroxylase was significantly decreased in EHBR as compared to control rats. Western blot analysis of liver microsomes of EHBR with antibodies to P-450IA2, P-450IIB1, P-450IIC11 and P-450IIIA2 showed that the amounts of P-450IIB1 and P-450IIIA2 in liver microsomes were significantly lower in EHBR than in control rats. These results indicated the form-specific alteration in the amounts of cytochrome P-450 in liver microsomes of EHBR. PMID- 1876755 TI - Lack of vagal influence on pulmonary visco-elasticity in puppies. AB - We recently demonstrated that most of the change in lung function following inhaled histamine in 8-10 week old puppies was due to changes in the tissue visco elastic properties and argued that vagally-mediated reflexes may be responsible for this phenomenon (Sly and Lanteri, J. Appl. Physiol. 1990; 68: 1562-1567). To test this hypothesis we compared 5 puppies treated with inhaled lignocaine or bilateral cervical vagotomy did not alter baseline pulmonary mechanics and there were no differences in the response to histamine challenge between the three groups. These results show that vagal reflexes, mediated via the central nervous system, are not involved in the response of the pulmonary tissues to inhaled histamine, but do not exclude the possible involvement of local axonal reflexes. PMID- 1876756 TI - Respiratory system mechanical behavior in the chicken. AB - We evaluated whether the avian respiratory system displays the same fundamental mechanical behavior during external forcing as found in mammals. We measured airway flow and pressures in the trachea, air sacs and thoracoabdominal cavity in 4 anesthetized-paralyzed roosters during sinusoidal volume oscillations at the trachea in the normal range of euthermic breathing frequency, f(0.2 to 1.0 Hz), and tidal volume, VT (10-50 ml). From the pressure and flow waveforms, we calculated resistance (R) and elastance (E) of the total respiratory system and its major compartments (lungs, air sacs and chest wall). E of the chest wall was minimum (147 cmH2O.L-1 +/- 7 SE) at 0.2 Hz-50 ml and was consistently, slightly lower than E of the total respiratory system over the entire range studied. Both elastances showed the same dependence on f and VT, increasing slightly with increasing f and decreasing with increasing VT. R of the chest wall was maximum (35.6 cmH2O.L- 1.sec-1 +/- 2.2 SE) at 0.2 Hz-10 ml and decreased with increasing f and VT, although the VT effect diminished at the higher f. E and R of the air sacs were much smaller than those of the chest wall, but showed similar f and VT dependencies. R of the lungs, due to resistance of the airways, was minimum (6.8 cmH2O.L-1.sec-1 +/- 1.5 SE) at 0.2 Hz-10 ml and increased with both f and VT. Total respiratory R reflected R of the air sacs and chest wall at low f and R of the lungs at high f. The f and VT dependencies of E and R in the chicken were strikingly similar to those measured in various types of mammalian respiratory tissues (Stamenovic et al. (1990) J. Appl. Physiol. 69: 973-988. We conclude that, despite important anatomical differences between species, avian and mammalian respiratory tissues exhibit fundamentally similar mechanical behavior. PMID- 1876757 TI - Gas physical properties and respiratory system resistance measured by flow interruption. AB - If the flow of gas at the airway opening of a tracheostomized dog is suddenly interrupted during expiration, the airway pressure exhibits a sudden very rapid rise, called delta Pinit, which has been shown previously to equal the resistive pressure drop across the airways in open-chest dogs, and to have a significant additional contribution from the tissues of the chest wall in intact dogs. In the present study we attempted to separate the contributions of airways and tissues to delta Pinit in intact dogs by performing flow interruptions with the lungs full of gas mixtures having different physical properties. A Moody plot (the Friction coefficient calculated using delta Pinit versus the Reynolds number) had a marked negative slope at Reynolds numbers up to 5 x 10(4), whereas the plot is predicted to have a slope close to zero at Reynolds numbers greater than 4 x 10(3) on the basis of purely fluid dynamic considerations. Assuming delta Pinit to be the result of a linear dependence of airway resistance on flow and a constant tissue resistance, we were able to account for the negative slope of the Moody plot. We also found that the values of airway and tissue resistances estimated from the data were very close to those estimated by more direct means in a previous study of delta Pinit. We conclude that it is possible to discern the separate effects of airway and tissue resistances in delta Pinit at high Reynolds numbers. PMID- 1876758 TI - Electrical and mechanical output of the expiratory muscles in anesthetized dogs. AB - In anesthetized intact and vagotomized dogs chest wall diameters, expiratory muscles' (EM) electrical activity, work, mean pressure and volume displacement contributed by EM contraction were assessed in the supine and upright posture during rebreathing, and during continuous positive pressure breathing (CPAP) in the supine posture. Corresponding inspiratory mechanical output variables were related to diaphragm activity. During resting breathing triangularis sterni and internal interosseous were more easily recruited than transversus abdominis and external oblique. EM activity increased with tilting, CPAP and rebreathing. Vagotomy depressed or abolished abdominal EM activity, with lesser effects on rib cage EM. Expiratory mechanical output grossly paralleled EM activity: it markedly depended on rib cage and abdominal EM coactivation, besides lung inflation and chest wall shape. Upper rib cage configuration at end-expiration never departed from the relaxation one, suggesting trivial effects of the triangularis sterni contraction. Lower chest wall distortion occurred almost regularly, so that much of EM activity was not converted into external work. In contrast with expiratory electromechanical relations, those for the diaphragm were always highly significant and independent of EM activation. PMID- 1876759 TI - Respiratory muscle activation by limb muscle afferent stimulation in anesthetized dogs. AB - In 10 chloralose anaesthetized and spontaneously breathing dogs, we assessed the effect of limb muscle afferents on the peak integrated EMG activities of the genioglossus, alae nasi, costal diaphragm, parasternal intercostal, triangularis sterni, and transverse abdominis muscles. The influence of vagal and baroreceptor afferents were eliminated by vagotomy and perfusion of carotid sinuses at a constant pressure. Muscle afferents were activated by stimulating the central end of the gastrocnemius nerve for 1 min at 40 Hz and at different voltages. Stimulation at voltages equal to 5, 10 and 20 times twitch-threshold increased minute ventilation to 165, 216 and 250% of pre-stimulation values, respectively, which was achieved by increasing breathing frequency (shortening of the inspiratory and expiratory times) and tidal volume. The activity of the parasternal intercostal and alae nasi muscles increased by a similar degree to that of the diaphragm while the activities of the genioglossus and transverse abdominis were augmented to a greater degree than that of the diaphragm. On the other hand, the motor drive to triangularis sterni increased significantly only at 20 times twitch-threshold and to a lesser degree than that to the diaphragm. These results suggest that upper airway, inspiratory and expiratory rib cage and abdominal muscles may be independently regulated. Differences in the sensitivity of these muscles to the activation of limb muscle afferents can be explained by a complex pattern of central projections of these afferents on the central respiratory controllers or by intrinsic properties of the motor output of these controllers. PMID- 1876760 TI - Reflex apnea induced by high-frequency oscillatory ventilation in rabbits. AB - In rabbits with intact vagus nerves, HFOV applied for 10-20 s caused apnea (i.e., respiratory arrest for as long as HFOV lasted) accompanied by tonic discharges of the diaphragm. To identify the vagal mechanisms involved in this type of apnea, the vagus nerves of anaesthetized rabbits were gradually cooled from 37 degrees C to 0 degree C, i.e., the vagal fibres were, corresponding to their diameter, successively blocked. At each temperature, the effects of HFOV on spontaneous breathing were compared with those of static lung inflation and deflation: Between 20 degrees C and 14 degrees C, the lung inflation reflex (mediated by pulmonary slowly adapting stretch receptors = PSR) was weakened or abolished, whereas the lung deflation reflex (mediated by rapidly adapting stretch receptors = RAR) was reinforced; the HFOV-induced apnea occurred less frequently, however, the accompanying diaphragmatic activity was enhanced. Between 14 degrees C and 5 degrees C, both HFOV and large static inflation caused a slight increase of breathing frequency in the majority of animals. Some animals, however, responded even below 14 degrees C by apnea to both HFOV and inflation, and, under these conditions, both HFOV- and inflation-induced apnea were accompanied by a pronounced tonic diaphragmatic activity. At 5 degrees C, the effects of HFOV as well as of inflation (except in two animals) and deflation were abolished. From the results we conclude that in rabbits the apnea during HFOV is mainly mediated by stimulation of PSR, and the concomitant tonic activity of the diaphragm is mainly due to stimulation of RAR, as it is reinforced with gradual blockade of PSR fibres and abolished when only non-myelinated fibres are intact. PMID- 1876762 TI - The oxygen debt hypothesis in juvenile rainbow trout after exhaustive exercise. AB - A 5 min bout of exhaustive exercise in 2-3 g rainbow trout resulted in a 2.0-2.5 fold increase in oxygen consumption (MO2), a 5-fold increase in whole-body lactate (LAC) levels and a near depletion in whole-body glycogen (GLY), ATP and creatine phosphate (CP) stores; glucose, ADP and AMP did not change. Recovery of MO2 and LAC was complete by 6 h, by which time GLY had stabilized at about 65% resting levels without further recovery through 24 h. Complete recovery of ATP required 1.0-1.5 h, whereas restoration of CP required only 5 min. The MO2 recovery curve was resolved into an initial fast component (t1/2 = 0.23 h) and a second slower component (t1/2 = 2.1 h), comprising approximately 20% and 80% respectively of the excess post-exercise oxygen consumption (EPOC). The fast component was satisfactorily accounted for by the standard components of the 'alactacid O2 debt'. However, the slow component could not be completely explained by changes in whole body LAC and GLY during recovery based on scenarios of either oxidation or GLY resynthesis as the primary fate of LAC. The classical 'O2 dept hypothesis' (Hill and Lupton, Quart, J. Med. 16: 135-171, 1923; Margaria et al., Am. J. Physiol. 106: 689-715, 1933) cannot be the complete explanation of EPOC in the trout. PMID- 1876761 TI - Effect of oxygen on potassium-excited ventilation in the decerebrate cat. AB - Raising arterial potassium ([K+]a) from ca. 3.5 to 6.5 mM, as occurs in heavy exercise, excites the arterial chemoreceptors and ventilation (VE) in anaesthetised cats. We have previously shown that the excitation of chemoreceptors by potassium is enhanced by hypoxia and abolished by hyperoxia, and here we show, in decerebrate cats, that the potassium-induced increase in VE is also abolished by hyperoxia. 100% oxygen was given abruptly in hypoxia (PETO2 ca. 50 Torr), with inspired gas tensions adjusted to give the same PETO2 and PETCO2 values before all tests on a given animal. Intravenous infusions of 150 mM KCl, which raised [K+]a from 3.9 +/- 0.3 mM to 7.4 +/- 0.3 mM (mean +/- SE), always excited hypoxic VE (42 +/- 8%; P less than 0.01). Hyperoxia, given during KCl infusion, reduced VE to a value not significantly greater (P greater than 0.27) than the hyperoxic value obtained before infusion. These results show that: (i) VE reflects the responses of chemoreceptors to K+, (ii) that abrupt hyperoxia removes the potassium-induced ventilatory drive, and (iii) that, in our experiments, K+ appears to have excited VE only via the peripheral chemoreceptors. PMID- 1876763 TI - Oxygen supply and uptake in tissue models with unequal distribution of blood flow and shunt. AB - The effects of unequal distribution of blood flow on O2 uptake are studied on a model composed of 3 tissues compartments with blood flow/O2 requirement ratios in the relation 9:3:1 (unequal blood flow model), a model with 33% shunt blood flow (shunt model), and a single compartment model without shunt (reference model). Diffusion limitation is assumed to be absent. Total blood flow (Q), arterial O2 content (CaO2) and O2 requirement of tissue are varied singly, and the resulting (mixed) venous O2 content (CvO2) and O2 uptake are calculated. In the reference model, CvO2 become zero, and O2 uptake starts falling below the O2 requirement, as soon as the O2 delivery (Q.CaO2) becomes smaller than the O2 requirement. In contrast, in the unequal blood flow model, decrease in the ratio O2 uptake/O2 requirement and in CvO2 sets in earlier, and proceeds more gradually, with decreasing Q or CaO2 or increasing O2 requirement; this is, because O2 delivery limitation sets in sequentially in the compartments, starting with the least perfused compartment. The shunt model behaves similarly to the reference model if Q or O2 requirement is varied, and to the unequal blood flow model if CaO2 is varied. Some features such as the parallel fall of O2 uptake and of CVO2 with decreasing CaO2, common to the unequal blood flow and shunt models, are similar to expected effects of diffusion limitation. Therefore, when the influence of diffusion limitation on tissue O2 supply is to be investigated quantitatively, the effects of a possible unequal distribution of blood flow must be taken into account. PMID- 1876764 TI - The effect of centrally administered adenosine on fetal breathing movements. AB - The central effects of the adenosine analogue L-2-N6-(phenylisopropyl) adenosine (L-PIA) on breathing movements was determined by making injections into the fourth ventricle in unanesthetized fetal sheep. Administration of 0.5 micrograms L-PIA reduced the percent time during which fetal breathing occurred from 48.0 +/ 5.2 (SEM) to 19.5 +/- 6.1. Inspiratory slope was reduced to 62 +/- 5.5 and to 43 +/- 5.7 percent of the control values when 0.2 and 0.5 micrograms L-PIA were given respectively. The effects of L-PIA on the percent time fetal breathing movements occurred and on inspiratory slope were prevented by the prior systemic administration of theophylline (plasma concentrations approximately 15 micrograms/ml). When the vehicle for L-PIA, dimethyl sulfoxide in Ringer solution was given into the fourth ventricle or when 0.5 micrograms L-PIA was given systemically, there was no effect on fetal breathing. None of these protocols resulted in a change in sagittal sinus blood pH, PO2 or, PCO2. These data indicate adenosine acts at the brain stem to depress fetal respiratory drive. PMID- 1876765 TI - Veterinary nuclear medicine. PMID- 1876766 TI - A personal history of veterinary nuclear medicine. PMID- 1876767 TI - Nuclear medicine equipment. PMID- 1876768 TI - Nuclear medicine artifacts and image quality. PMID- 1876769 TI - Thyroid scintigraphy in small animals. PMID- 1876771 TI - Liver scintigraphy: application in small animals. PMID- 1876770 TI - The principles and practice of bone scintigraphy in small animals. PMID- 1876772 TI - Kidney scintigraphy. PMID- 1876773 TI - Statistical methods in biopharmacy. Satellite meeting of the 47th World Session of the International Statistical Institute. Paris, 7-8 September 1989. Proceedings. PMID- 1876776 TI - On the use of historical controls in the analysis of laboratory data. AB - Our purpose is to propose a method of data analysis incorporating historical controls. It consists of three steps of hypothesis testing procedure. The first step is the check of concurrent controls. The second is the significance testing of treatment groups in comparison with historical controls which are composed of negative and positive controls. The third is the significance testing of a linear trend of the dose-response relationship. The superiority of the proposed procedure is also verified. PMID- 1876774 TI - Using empirical Bayes methods in biopharmaceutical research. AB - A compound sampling model, where a unit-specific parameter is sampled from a prior distribution and then observed are generated by a sampling distribution depending on the parameter, underlies a wide variety of biopharmaceutical data. For example, in a multi-centre clinical trial the true treatment effect varies from centre to centre. Observed treatment effects deviate from these true effects through sampling variation. Knowledge of the prior distribution allows use of Bayesian analysis to compute the posterior distribution of clinic-specific treatment effects (frequently summarized by the posterior mean and variance). More commonly, with the prior not completely specified, observed data can be used to estimate the prior and use it to produce the posterior distribution: an empirical Bayes (or variance component) analysis. In the empirical Bayes model the estimated prior mean gives the typical treatment effect and the estimated prior standard deviation indicates the heterogeneity of treatment effects. In both the Bayes and empirical Bayes approaches, estimated clinic effects are shrunken towards a common value from estimates based on single clinics. This shrinkage produces more efficient estimates. In addition, the compound model helps structure approaches to ranking and selection, provides adjustments for multiplicity, allows estimation of the histogram of clinic-specific effects, and structures incorporation of external information. This paper outlines the empirical Bayes approach. Coverage will include development and comparison of approaches based on parametric priors (for example, a Gaussian prior with unknown mean and variance) and non-parametric priors, discussion of the importance of accounting for uncertainty in the estimated prior, comparison of the output and interpretation of fixed and random effects approaches to estimating population values, estimating histograms, and identification of key considerations in the use and interpretation of empirical Bayes methods. PMID- 1876777 TI - A statistical procedure for the estimation of accuracy parameters in interlaboratory studies. AB - Interlaboratory studies are conducted to estimate the accuracy of methods of laboratory measurements. The standard parameters used to describe this accuracy are the repeatability and the reproducibility. Usually variance components models are used to estimate these parameters. If the model assumptions are violated the resulting estimates for reproducibility and repeatability may, however, be biased. A new method of residual analysis in variance components models- developed by the author--may be used to detect violations of the model assumptions. If the residual analysis indicates that the model assumptions are violated, a simple robust method--which makes fewer assumptions--may be used for the estimation of accuracy parameters. The application of this residual analysis is demonstrated using data of an interlaboratory study. Graphical methods play an important role in the evaluation of the residuals. The analysis of the residuals uses methods similar to those used for the analysis of Studentized residuals in the linear model. The estimates obtained by the variance components model and the simple robust method are compared. The results of the residual analysis may be used to decide which of the two estimates can be considered more appropriate. The necessity of residual analysis in the analysis of interlaboratory studies by variance components models is pointed out. Potential hazards inherent to residual analysis in variance components models are discussed. Conclusions for the analysis of interlaboratory studies are drawn. PMID- 1876775 TI - The construction of biochemical reference ranges and the identification of possible adverse drug reactions in the elderly. AB - In the assessment of adverse drug reactions (ADRs) it is important to establish what is a normal range of values for a given biochemical measurement. Furthermore, such ranges need to be specific to the study population, for example, the elderly. A mixture of Gaussian distributions has been used in the construction of the reference ranges with maximum likelihood used to obtain estimates of the unknown parameters. With this approach, well-defined reference ranges have been established. Brief details are given of the numbers of ADRs identified in the study population using these ranges. PMID- 1876778 TI - Estimation of the mean and standard deviation using order statistics. AB - Estimation of the mean and standard deviation of a distribution using linear combinations of the order statistics of a censored sample is discussed. Existing methods are compared with the optimal estimator of this type and new approximations to the optimal estimator are proposed. Their performances in the presence of outliers are assessed by means of simulation. PMID- 1876779 TI - Analysis of the crossover design in the presence of residual effects. AB - When a residual effect is suspected in a two-period crossover trial, an analysis of the first-period data is often chosen instead of the potentially biased crossover analysis. This paper indicates how the usual crossover test has to be interpreted correctly and that its bias has two different consequences, namely a conservative or a liberal test decision if a positive (carryover) or a negative (withdrawal) residual effect exists. A multiple testing procedure is presented allowing for simultaneous crossover and first-period analysis controlling the experimental error rate. This procedure together with the correct interpretation of the crossover test enables many useful applications of crossover designs. PMID- 1876780 TI - A random effects model for ordinal responses from a crossover trial. AB - Crossover studies have been successfully conducted in the case of continuous responses. Existing procedures of analysis for ordinal responses, on the other hand, are rarely satisfactory unless strict, usually unrealistic, assumptions are made. In this paper we investigate a random effects model and show that the model is simple and general. Interpretation of parameters is easy, though with a complicated fitting procedure. PMID- 1876781 TI - Determination of optimal designs using linear models in crossover trials. AB - This study determines the optimal designs for crossover trials with fixed size of population, in order to estimate contrasts between two treatment effects, for various numbers of periods. The problem is approached in the framework of a linear model, taking into consideration the structure of a variance matrix constructed from two random sources: linked-to-subject random effect and linked to-measurement random error. Different models, as well as different optimality criteria, are considered. For example, when two periods are planned, for the criterion of the minimization of the variance of the treatment-effect estimator, in the presence of residual effect, the optimal design corresponds to four groups of sequences, (T1, T2), (T2, T1), (T1, T1), (T2, T2); without residual effect it corresponds to two groups, (T1, T2), (T2, T1). Optimal designs are given for the comparison of two treatments when using three or four periods. PMID- 1876782 TI - Interim analysis in clinical trials. AB - The early development of experimental design discouraged a sequential approach to the analysis of data, yet this seems a natural form of scientific enquiry. Clinical trial investigators should continuously monitor the quality of their techniques, but will often wish to delegate data monitoring to an independent group. The history and functions of data monitoring committees (DMCs) are reviewed. DMCs come in many shapes and sizes. They will need to consider many aspects of the data before making recommendations to the investigators, who have ultimate responsibility for early termination or protocol changes. Statistical issues form part of the assessment, and will involve management, safety and efficacy. Two broad approaches to early stopping are (i) the demonstration of strong evidence that a treatment effect falls above or below some critical value (not necessarily zero); (ii) stochastic curtailment based on prediction of final results. The latter is examined somewhat critically. Most trials will involve group sequential analyses at discrete time points. The effect of repeated data inspection on (i) is well known, although its relevance is debatable. Bayesian and likelihood methods do not entirely remove the difficulty. PMID- 1876783 TI - Step-down multiple tests for comparing treatments with a control in unbalanced one-way layouts. AB - We show how a well-known multiple step-down significance testing procedure for comparing treatments with a control in balanced one-way layouts can be applied in unbalanced layouts (unequal sample sizes for the treatments). The method we describe has the advantage that it provides p-values, for each treatment versus control comparison, that take account of the multiple step-down testing nature of the procedure. These joint p-values can be used with any value of alpha, the fixed type I family wise error rate bound, that may be specified by the investigator. To determine the p-values, it is necessary to compute a multivariate Student t integral, for which a computer program is available. This procedure is more powerful than the step-down Bonferroni procedure of Holm and the single-step procedure of Dunnett. An example from the pharmaceutical literature is used to illustrate the procedure. PMID- 1876784 TI - Some extensions to a new approach for interim analysis in clinical trials. AB - There already exists many methods for group sequential analysis of clinical trials. A new approach suggests to preserve the overall type I error alpha by requiring that a succession of interim analyses be significant at the alpha level. In this paper, this procedure is extended. A rule for early acceptance of H0 is presented, with an extension for flexible number and times of analyses. A real example is given. PMID- 1876785 TI - Individual bioequivalence: what matters to the patient. AB - Current procedures for assessing the bioequivalence of two formulations are based on the concept of average bioequivalence. That is, they assess whether the average responses between individuals on the two formulations are similar. We show first that average bioequivalence is not sufficient to assure that an individual patient could be expected to respond similarly to the two formulations. To have such reasonable assurance requires a different notion of bioequivalence; individual (or within-subject) bioequivalence. Second, we propose a simple statistical procedure for assessing individual bioequivalence. This decision rule, TIER (test of individual equivalence ratios) requires the specification of the minimum proportion of subjects in the applicable population for which the two formulations being tested must be bioequivalent (a regulatory decision). The TIER rule is summarized in terms of the minimum number of subjects with bioavailability ratios falling within the specified equivalence interval necessary to be able to claim bioequivalence for given sample size and type I error. We recommend that the corresponding lower bounds (one-sided confidence intervals) for the proportion of bioequivalent subjects be calculated. PMID- 1876786 TI - Sample sizes for bioequivalence studies. AB - In recent years a number of decision rules, based on sound statistical principles, have been proposed for deciding if a test formulation is bioequivalent to a reference formulation. The decision rule based on confidence intervals has been accepted by regulatory agencies, at least by the Food and Drug Administration of the United States. A useful property of this decision rule is that the regulatory agency need not require a certain sample size, since the level of protection against wrongly deciding bioequivalence is set by the choice of the alpha level used to compute the confidence intervals. The manufacturer claiming bioequivalence is concerned about sample size, for sample size determines the probability of falsely deciding non-bioequivalence when the test formulation does indeed have an acceptable relative bioavailability. Curves of probability of rejecting bioequivalence have been computed for error coefficient of variation of 10, 20 and 30 per cent, for relative bioavailability from 70 to 130 per cent, and for protection levels of 90 and 95 per cent. These curves can be used for choosing the sample size for a bioequivalence study. PMID- 1876787 TI - Problems induced by meta-analyses. AB - Over 150 meta-analyses of randomized control trials have so far been published in the English language, and new ones are appearing at a rate of over fifteen per year. This explosion of a relatively new method of evaluating clinical medicine presents a number of challenges to statisticians and those responsible for health care policy. The pitfalls of retrospective research must be avoided, and the quality of the original trials should be evaluated. Heterogeneity of the control event rates and the treatment differences need to be dealt with statistically. Most important are the problems raised by the need to update meta-analyses as new trials are published. PMID- 1876788 TI - Maximum likelihood techniques applied to method comparison studies. AB - One component of method comparison studies is the assessment of relative bias. Most authors use ordinary regression techniques for this purpose. The potential inadequacies in this approach are highlighted and a more generally applicable maximum likelihood technique proposed. The properties of the various methods of estimation are obtained by means of a simulation study, using a variety of different within-assay precision profiles. PMID- 1876789 TI - Analysis of phase II clinical trials in haematology and oncology: comparison of the triangular test to the usual methods. AB - Phase II cancer clinical trials are non-comparative trials which are designed to determine whether the response rate p to the treatment under study is greater than a certain value p0, that is, to test H0, given by p less than or equal to p0 against H1 given by p greater than po. By choosing type I error alpha and the power 1-beta and by specifying H1, that is, by choosing a clinically relevant improvement p1), one can compute the number of patients N to be included for a fixed-sample approach. Various other approaches have been proposed such as multistage methods and Wald's continuous sequential probability ratio test (SPRT). As an alternative approach, we extended the triangular test (TT), proposed by Whitehead for comparative trials, to the situation of non-comparative trials with a binary outcome. We expressed H0 and H1 in terms of the log odds ratio statistics, namely log [p(1-p0)/p0-(1-p)]. With this choice, the two statistics of interest, Z and V, have simple expressions: Z is the difference between the observed number of positive outcomes and the expected number under H0 and V is the variance of Z under H0. After every group of n patients, Z is plotted against V, and the trial proceeds until a boundary is crossed. In our simulations, type I error alpha and the power 1-beta were close to nominal values with the TT and the average sample size was close to Wald's continuous SPRT and compared favourably with the multistage methods proposed by Herson and Fleming. Given its statistical properties and its easy use, the TT should be considered for planning and analysing cancer phase II trials. PMID- 1876790 TI - Random models for margins of a 2 x 2 contingency table and application to pharmacovigilance. AB - The identification of new adverse drug reactions is often tricky. For a given case, the relationship between drug exposure and symptom occurrence is usually questionable. It could be investigated statistically from a series of drug-event association cases with an independence test between the two variables. Analysing the related 2 x 2 contingency table obviously requires knowledge of its margins. However this information is often not available. We develop a calculation of the P-value by choosing some random models for the unknown margins. Under the hypothesis of independence, a negative binomial distribution for the frequency of the drug-event association cell is obtained, exactly or approximately. This method allows investigation of the causal relationship when some parameters, as incidence of the symptom in the population, are uncertain. An example is presented. PMID- 1876791 TI - The potential for spread of HIV in the heterosexual population in Norway: a model study. AB - A simulation model is used to investigate the potential for indigenous spread of human immunodeficiency virus (HIV) in the heterosexual population in Norway. The heterosexual population is grouped according to age, sex and whether paired or single. Estimates of various parameters of sexual behaviour are taken from a population-based questionnaire study. The questionnaire was sent to a random sample of 10,000 individuals, with a response rate of 63 per cent. The main simulation result is that with no inflow of infection from other risk groups, the heterosexual epidemic will decline if the average transmission probability per intercourse is 1 per cent or less. This result is insensitive to changes in the initial conditions. It is sensitive to changes in sexual behaviour, and to the shape of the transmission probability distribution. A review of empirical partner study data indicates an average transmission probability about 0.1 per cent per intercourse when no transmission modulating cofactors are present. It is concluded that with present sexual behaviour, the indigenous spread of HIV is not likely to sustain an epidemic in the Norwegian heterosexual population. PMID- 1876792 TI - An estimating equation approach for the analysis of case-control studies with exposure measured at several levels. AB - Liang gave an extension of the Mantel-Haenszel estimating procedure for a common odds ratio to logistic regression models. It is applicable to case-control studies with multiple exposure levels, which yield K 2 x J tables. This paper provides variance and covariance estimators, which are consistent in both sparse data and large-strata, for Liang's estimating functions in the K 2 x J tables case, and proposes an approximate confidence interval method for the common odds ratios. PMID- 1876793 TI - Analyses of black and white differentials in the age trajectory of mortality in two closed cohort studies. AB - We examine the relationship of age to mortality in blacks and whites in two cohort studies, the 20-year follow-up of the Evans County, Georgia. Study population and the 25-year follow-up of the Charleston Heart Study population. We conducted analyses with two parametric forms of hazard models (Gompertz and Weibull) for total mortality experience and considered the fit of the two hazard models in each study both separately and with the data pooled. We evaluated the robustness of conclusions about differences in the age pattern of mortality for blacks and whites by comparing results from the two hazard models. Where the tests were non-nested, we used an information-based statistic (AIC) to compare the fit of the models to the data. Results were robust to the selection of the hazard function, that is both models provided evidence that mortality rates at younger ages were lower for white than black females but that mortality rates increased more rapidly with age for white females. The absolute differences and the differences in the rates of increase were in the same direction, but smaller, for males. Though both models represented the general features of mortality patterns, the information statistic suggested better performance of the Gompertz function. The Gompertz function was also less sensitive to the initial age of determination of mortality exposure. PMID- 1876794 TI - Assessing the influence of reversible disease indicators on survival. AB - In a randomized clinical trial of the effect of prednisone versus placebo on survival in patients with liver cirrhosis, follow-up visits were scheduled after 3, 6 and 12 months of treatment and thereafter once a year. At each follow-up the prothrombin index, a measure of liver function, was recorded and scored as either low or normal. The interaction between treatment and prothrombin index was analysed using a three-state illness-death model with recovery. The continuous time Markov process model with constant or piecewise constant intensities suggested by Kay allows inference to proceed even though the status of the disease indicator, here the prothrombin index, is only known at the time of each visit and not between visits. We compare the analysis with the theoretically incorrect, but practically rather common approximation, where the status of the disease indicator is assumed to remain constant from one visit until just before the next. Under this approximation both standard parametric methods and non parametric approaches developed by Aalen and Johansen are available. PMID- 1876795 TI - Estimating standardized parameters from generalized linear models. AB - Although the traditional unrestricted ('non-parametric') estimators of directly standardized rates and rate differences remain unbiased in sparse data, they tend to suffer from instability (low precision). As a result, many authors have proposed more precise estimators based on parametric models for the rates. This paper provides a general approach for constructing estimators of standardized parameters using generalized linear models, and shows that, in some common special cases, these model-based ('smoothed') estimators can have an exceptionally simple form. PMID- 1876796 TI - Generalized Norton-Simon models of tumour growth. AB - This paper considers the analysis of serial data on the growth of tumours in laboratory rodents. I propose a model-a generalization of the tumour growth model of Norton and Simon-that leads to a rich family of growth and decay curves. The model assumes that unperturbed growth follows the generalized logistic form; it accommodates time-varying treatment effects through an effective dose function. I fit two such models to data on a human prostate tumour growing in nude mice and compare the fitted curves and dose functions with a non-parametric curve and dose function estimated from a cubic spline model. All three models account for both random animal effects and autocorrelation. Monte Carlo results suggest that (a) maximum likelihood estimates of growth parameters are biased, although not severely, and (b) standard errors are conservative in small samples but become increasingly accurate in larger samples. PMID- 1876797 TI - Evaluation of statistical methods for monitoring periodontal disease. AB - Three methods for detecting the progression of periodontal disease based on the change in attachment level on teeth are compared from a statistical point of view. Regardless of gradual or burst disease progression theories, the regression method is found to be the most efficient way to detect changes. The exact false alarm rate is computed when the decision is based on the maximum regression coefficient at all sites during several visits. PMID- 1876798 TI - The analysis of failure time data in crossover studies. AB - Clinical trials of new drugs in the treatment of angina pectoris frequently make use of exercise tests to evaluate efficacy. The crossover design is often employed. The methods commonly used to analyse the various exercise times, for example, 'time to pain', are insensitive and potentially biased by the manner in which they deal with the censored nature of the data. Survival analysis can be adapted for use in crossover trials, both in a relatively simple way, and also through the full power of the Cox model. This is considerably more sensitive and not subject to the same bias. This methodology leads to the use of median survival times to illustrate treatment effects and this provides a practical interpretation of clinical relevance. The estimation of median survival times in crossover trials poses some special problems. The methodology is illustrated throughout by means of a specific two-period example in which atenolol was compared with the combination of atenolol and nifedipine. The three-period design is also briefly discussed. PMID- 1876799 TI - Recovery of inter-block information in cross-over trials. AB - For cross-over designs, we show that one can recover information on direct and/or residual treatment effects from an inter-block (patients as blocks) analysis as is done in an incomplete block design. By combining the intra- and inter-block estimates, we obtain the generalized least squares estimate. In analysing cross over trials, we recommended this approach provided the between-patient variance component can be estimated efficiently. PMID- 1876800 TI - Approximate multinormal probabilities applied to correlated multiple endpoints in clinical trials. AB - Clinical trials with multiple endpoints incur increased familywise type I errors. The Bonferroni correction is a common method used to modify the p-values to account for multiple significance testing. For independent endpoints the Bonferroni method is slightly conservative whereas with high correlation the conservatism is extreme, as demonstrated by Pocock et al. This paper presents a procedure which allows for the correlation present, whilst adjusting the multiple p-values. The method is based on an approximation derived for multinormal probabilities. PMID- 1876801 TI - A quasi-exact test for comparing two binomial proportions. AB - The use of the Fisher exact test for comparing two independent binomial proportions has spawned an extensive controversy in the statistical literature. Many critics have faulted this test for being highly conservative. Partly in response to such criticism, some statisticians have suggested the use of a modified, non-randomized version of this test, namely the mid-P-value test. This paper examines the actual type I error rates of this test. For both one-sided and two-sided tests, and for a wide range of sample sizes, we show that the actual levels of significance of the mid-P-test tend to be closer to the nominal level as compared with various classical tests. The computational effort required for the mid-P-test is no more than that needed for the Fisher exact test. Further, the basis for its modification is a natural adjustment for discreteness; thus the test easily generalizes to r x c contingency tables and other discrete data problems. PMID- 1876802 TI - Baseline comparisons in randomized clinical trials. PMID- 1876803 TI - Testing for a change point in registry data with an example of hypospadias. PMID- 1876804 TI - [Drugs are overrunning us. A study performed among nursing students]. PMID- 1876805 TI - [Food handlers. A practical study]. PMID- 1876806 TI - [Considerations on old age]. PMID- 1876807 TI - [Undergraduate education in community health nursing. Apropos an active method]. PMID- 1876808 TI - [On the occasion of the II National Meeting of Primary Nursing Care. Do we believe what we are doing?]. PMID- 1876809 TI - [An interesting initiative: Group 5. The development of primary health care in the community of Valencia]. PMID- 1876810 TI - [The needle for health use with a safety device. An interesting innovation for nursing]. PMID- 1876811 TI - [The Drug Law]. PMID- 1876812 TI - [The management of hospital solid wastes from an environmental health perspective]. PMID- 1876813 TI - [Differences in taking the arterial pressure]. PMID- 1876814 TI - [The nutritional status of the elderly. Some considerations on its assessment]. PMID- 1876815 TI - [Hospital to primary care diversion. The whys of a reality]. PMID- 1876816 TI - [A stretcher bed for transporting critical patients]. PMID- 1876818 TI - Hepatitis B virus. PMID- 1876817 TI - [Continuing education. 61. Subject: administration. Topic: general concepts on the Spanish health system]. PMID- 1876819 TI - Love and terror. Is a chemical messenger key to treating Alzheimer's? PMID- 1876820 TI - Gas vaccine. Bioengineered immunization could shield against nerve gas. PMID- 1876821 TI - Mind reader. Do personality tests pick out bad apples? PMID- 1876822 TI - Seeking senescence. Specific genes may control how many times a cell can divide. PMID- 1876824 TI - A press release on dioxin sets the record wrong. PMID- 1876823 TI - A gentler therapy? Retinoic acid turns off a form of leukemia. PMID- 1876825 TI - Molecular zippers in gene regulation. PMID- 1876826 TI - Cancer and poverty. PMID- 1876827 TI - Prescription drug prices. PMID- 1876828 TI - Surgeon-warriors? PMID- 1876829 TI - Hints emerge from the Gallo Probe. PMID- 1876830 TI - Popovic blasts accusers, demands report be withdrawn. PMID- 1876831 TI - The Gallo factor: questions remain. PMID- 1876832 TI - Penicillin's forgotten man: Norman Heatley. PMID- 1876833 TI - Convergence of Ets- and notch-related structural motifs in a heteromeric DNA binding complex. AB - Analysis of the heteromeric DNA binding protein GABP has revealed the interaction of two distinct peptide sequence motifs normally associated with proteins located in different cellular compartments. The alpha subunit of GABP contains an 85 amino acid segment related to the Ets family of DNA binding proteins. The ETS domain of GABP alpha facilitates weak binding to DNA and, together with an adjacent segment of 37 amino acids, mediates stable interaction with GABP beta. The beta subunit of GABP contains four imperfect repeats of a sequence present in several transmembrane proteins including the product of the Notch gene of Drosophila melanogaster. These amino-terminal repeats of GABP beta mediate stable interaction with GABP alpha and, when complexed with GABP alpha, directly contact DNA. These observations provide evidence for a distinct biochemical role for the 33-amino acid repeats, and suggest that they may serve as a module for the generation of specific dimerization interfaces. PMID- 1876834 TI - Purification of an allene oxide synthase and identification of the enzyme as a cytochrome P-450. AB - Fatty acid hydroperoxides (lipoxygenase products) are metabolized to allene oxides by a type of dehydrase that has been detected in plants, corals, and starfish oocytes. The allene oxides are unstable epoxide precursors of more complex products such as jasmonic acid, the plant growth hormone. Characterization of the dehydrase enzyme of flaxseed revealed that it is a 55 kilodalton hemoprotein. The spectral characteristics of this dehydrase revealed it to be a cytochrome P-450. It operates with the remarkable activity of greater than or equal to 1000 turnovers per second. The results establish a new catalytic activity for a cytochrome P-450 and illustrate the cooperation of different oxygenases in pathways of fatty acid metabolism. PMID- 1876835 TI - Specificity for aminoacylation of an RNA helix: an unpaired, exocyclic amino group in the minor groove. AB - An acceptor stem G3.U70 base pair is a major determinant of the identity of an alanine transfer RNA. Hairpin helices and RNA duplexes consisting of complementary single strands are aminoacylated with alanine if they contain G3.U70. Chemical synthesis of RNA duplexes enabled the introduction of base analogs that tested the role of specific functional groups in the major and minor grooves of the RNA helix. The results of these experiments indicate that an unpaired guanine 2-amino group at a specific position in the minor groove of an RNA helix marks a molecule for aminoacylation with alanine. PMID- 1876836 TI - Identification of Ets- and notch-related subunits in GA binding protein. AB - Recombinant cDNA clones that encode two distinct subunits of the transcription factor GA binding protein (GABP) have been isolated. The predicted amino acid sequence of one subunit, GABP alpha, exhibits similarity to the sequence of the product of the ets-1 protooncogene in a region known to encompass the Ets DNA binding domain. The sequence of the second subunit, GABP beta, contains four 33 amino acid repeats located close to the NH2-terminus of the subunit. The sequences of these repeats are similar to repeats in several transmembrane proteins, including Notch from Drosophila melanogaster and Glp-1 and Lin-12 from Caenorhabditis elegans. Avid, sequence-specific binding to DNA required the presence of both polypeptides, revealing a conceptual convergence of nuclear transforming proteins and membrane-anchored proteins implicated in developmentally regulated signal transduction processes. PMID- 1876837 TI - Design and synthesis of a mimetic from an antibody complementarity-determining region. AB - A technique for producing non-peptide compounds (mimetics) of designed specificities was developed that permitted the synthesis of a conformationally restricted molecule that mimicked the binding and functional properties of monoclonal antibody (MAb) 87.92.6, which recognizes the reovirus type 3 cellular receptor. Binding of either MAb 87.92.6, peptide analogs, or 87.1-mimetic to the cellular receptor inhibited cellular proliferation. The mimetic was a synthetic beta-loop structure that mimics the second complementarity-determining region of the MAb. These studies may lead to strategies for the synthetic design of antibody complementarity regions, ligands, and other pharmacologically active agents that are water soluble, resistant to proteolysis, and nonimmunogenic. PMID- 1876838 TI - Photoperiodism and effects of indoleamines in a unicellular alga, Gonyaulax polyedra. AB - Mediation of photoperiodic effects by indoleamines, especially melatonin, is known in higher vertebrates. A similar mechanism may occur in a unicellular alga, the dinoflagellate Gonyaulax polyedra. This organism entered the dormant stage of a cyst upon short-day treatment at lowered temperatures. Interruption of darkness by 2 hours of light prevented cyst formation, even when the overall duration of light was the same as in cyst-inducing short days. When given in a noninducing photoperiod, melatonin and an analog, 5-methoxytryptamine, substances that had previously been shown to occur in Gonyaulax, provoked cyst formation. Methoxylated indoleamines may play a role as mediators of darkness in this unicellular, in a similar way as in vertebrates, suggesting a common biochemical basis of photoperiodism. PMID- 1876839 TI - Shaking the family tree. PMID- 1876840 TI - Women lab heads. PMID- 1876841 TI - EC biotechnology policy. PMID- 1876842 TI - Boston loses 1992 AIDS meeting. PMID- 1876843 TI - Jawboning prehistory. PMID- 1876844 TI - Policy-making: getting better data. PMID- 1876845 TI - Forecasting the global AIDS epidemic. PMID- 1876846 TI - Sigma factor relatives in eukaryotes. PMID- 1876847 TI - Evidence of lactate dehydrogenase-B allozyme effects in the teleost, Fundulus heteroclitus. AB - The evolutionary significance of protein polymorphisms has long been debated. Exponents of the balanced theory advocate that selection operates to maintain polymorphisms, whereas the neoclassical school argues that most genetic variation is neutral. Some studies have suggested that protein polymorphisms are not neutral, but their significance has been questioned because one cannot eliminate the possibility that linked loci were responsible for the observed differences. Evidence is presented that an enzymatic phenotype can affect carbon flow through a metabolic pathway. Glucose flux differences between lactate dehydrogenase-B phenotypes of Fundulus heteroclitus were reversed by substituting the Ldh-B gene product of one homozygous genotype with that of another. PMID- 1876848 TI - Proliferative breast disease: diagnosis and implications. PMID- 1876849 TI - [Respiratory disorders in trauma patients. Pulse oximetry as an extension of prehospital diagnostic and therapeutic possibilities]. AB - The early diagnosis and adequate treatment of respiratory complications in trauma cases has a decisive influence upon the patients' posttraumatic development. Pulse oximetry enables us to evaluate and monitor the prehospital respiratory situation objectively for the first time. Within a prospective study conducted from October 1988 to October 1989 in 336 unselected, primarily traumatized, emergency patients rescued by our "SAR Ulm 75" helicopter team, to determine the possibilities and limitations of this method, we maintained continuous pulse oximetric monitoring in all cases. The practical applicability and functional stability of the pulse oximeters used were adequate. On-the-spot intubation was necessary in 45% of the patients (or they were intubated prior to our taking over). Oxygen inhalation by nasal cannula was needed in 55%. While not being decisive for immediate intubation, monitoring with a pulse oximeter does play an essential role in controlling respiratory therapy. In 32% of our cases, pulse oximetric monitoring permitted early adjustment of the respiratory therapy to meet the patients requirements. This method is of special value in disclosing life-threatening respiratory complications (9.3%) i.e., valve pneumothorax. Within a group with a high percentage of multiple traumas (27%) and thorax traumas (39%), this was of enormous assistance in the differential diagnosis. Level and rate of increase of oxygen saturation can be an indication of the severity of a thorax trauma. The limitations of pulse oximetric monitoring, especially those resulting from low peripheral perfusion in trauma cases (7 patients), are fairly rare. PMID- 1876850 TI - [The relative value of electromyography (EMG) in the evaluation of the results of surgical repair of biceps tendon rupture in the arm]. AB - Ten patients treated for rupture of a biceps tendon were re-evaluated 2 years or longer after surgery. Four patients complained of loss of strength and increased fatigue. The concentric EMG examination and the technically more demanding Macro EMG technique showed normal motor unit action potential patterns in the muscle operated on and in the contralateral muscle used as control. The symptom weakness could not be explained by myopathic or neurogenic muscle changes. Concentric EMG had the same diagnostic yield as Macro EMG in this study. Concentric EMG is sufficient to scan for pathological findings within the biceps muscle. If any are present they should initially be interpreted as evidence of a further pathologic condition and not as sequelae of the tendon rupture. PMID- 1876851 TI - [Tarsal tunnel syndrome. Nerve compression syndrome in the foot]. AB - Pathological changes in sensation over the sole of the foot do not always correspond to the full area of distribution of the posterior tibial nerve. Some neurologists advise separate examination of the tibial nerve, the medial and lateral plantar nerves, in order to ascertain whether either or both might be affected. 60 preparations of cadaveric feet in the Department of Anatomy were examined. Using a measuring grid, the position and size of the nerves in the tarsal tunnel were assessed and the facial band which define and divide the osteofibrous canal delineated. The corners of the measuring grid were the tip of the medial malleolus (A), the tip of the calcaneal tubercle at its greatest distance from the medial malleolus (B) and the tuberosity of the navicular bone (C). These points can also be clearly identified clinically. They define a triangle whose sides A-B and B-C are of constant equal length and whose base A-C varies little. The operative approach includes a T-shaped incision of the retinaculum. The vertical line of the T lies underneath the skin incision. The horizontal line corresponds with the upper border of the abductor hallucis muscle. The upper border of the abductor hallucis is defined and the muscle retracted medially to expose the deep fascia. This layer is removed together with the connective tissue bridge which stretches between the fascia and the calcaneus. The plantar nerves are discovered and run to the sole of the foot without further obstruction. PMID- 1876852 TI - [Ultrasound evaluation of multidirectional instability of the shoulder]. AB - In a prospective study we evaluated the active a-p translation of the humeral head in the glenoid socket and the passive cranio-caudal translation of the humeral head in relation to the acromion. In 150 healthy volunteers we documented normative data. These results were compared with the data recorded in 34 patients with multidirectional shoulder instabilities. With the arm adducted or in 90 degrees flexion we found no statistically significant differences between volunteers and patients or between the sexes, or between the dominant and the non dominant extremity in the relationship between the humeral head and the dorsal brim of the glenoid. In 90 degrees abduction and neutral rotation of the arm the dorsal overhang of the humeral head in relation to the dorsal brim of the glenoid was 1.5 mm (+/- 3.5 mm) on the dominant and 1.9 mm (+/- 3.4 mm) on the non dominant side in the volunteer group. However, in patients with multidirectional shoulder instability the humeral head demonstrated such a high degree of a.-p. translation that we found a ventral overhang of 2.9 mm (+/- 3.7 mm) on the dominant and 0.7 mm (+/- 4.6 mm) on the opposite side. These differences to the volunteer group were statistically highly significant (P less than 0.001). In patients the difference between the dominant and the non-dominant extremity was also significant (P less than 0.05). After active movement into the 90 degree abducted and external rotated position of the arm the differences between volunteers and patients increased, until finally the differences in patients between the dominant and the non-dominant side were highly significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876853 TI - [Interpretation of MR tomography findings in trauma surgery]. AB - MR-Imaging is well established as the most sensitive method for the diagnosis of avascular necrosis of the femoral head. In this paper preliminary results are analyzed in an attempt to clarify whether as in a vascular necrosis of the femoral head. MR changes after trauma or surgery allow conclusions concerning the vitality of the bone. Comparison of clinical, MR and histological findings revealed that we cannot yet differentiate between fibrosis of the bone marrow with sustained vitality of the osteocytes and bone necrosis. Therefore, conclusions with implications for therapy should be drawn with extreme care. PMID- 1876854 TI - [Gunshot wounds. Therapeutic possibilities in a developing African country]. AB - This report is based on experience with the treatment of 135 patients who had sustained mainly gunshot injuries but also injuries from mines and hand grenades. The different sorts of the therapy were directly dependent on the different injury causes. Second- and third-grade fractures caused by middle and high velocity projectiles were treated by the open method, external fixation, debridement and draining. The therapy of choice is the application of a fixateur externe (external fixation). The prognosis after fixation with further treatment as needed was very good, even when not performed until several weeks after the injury, especially in the restitution of extremity continuity, which can sometimes help to prevent unnecessary amputations, especially of the upper extremities. PMID- 1876855 TI - [Tissue-preserving ventral compression osteosynthesis of dens axis fractures using endoscopy and special instruments]. AB - Endoscopic operations are tissue-preserving operative methods, which are increasing constantly in importance. Lag screw osteosynthesis is suitable for performance as an endoscopic operation with specially designed instruments. We have developed a set that allows lag screw osteosynthesis into the axis of the dens. Under endoscopic view the soft tissues are divided and a tube is placed through which the screw is inserted with the aid of an image intensifier. Two patients have so far been operated on in this way, both without complications. PMID- 1876856 TI - [Experience with plating of intra-articular fractures of the calcaneus]. AB - There have been various attempts to improve the results of treatment of fractures of the calcaneus in recent decades. Descriptions of conservative treatment with plaster cast, functional treatment and several methods of closed and open reduction and stabilization have been published. We believe that, especially in young patients, intraarticular fractures with depression of the posterior articular facet should be treated by open anatomical reduction, autologous bone grafting and stabilization with plates. In our clinic 15 fractures of the calcaneus have been treated in this manner in the last few years, and the results are very satisfying. PMID- 1876857 TI - [Elbow dislocation with fracture of the coronoid process and comminuted fracture of the radius head]. AB - In fractures of the elbow with an associated fracture of the coronoid process, the size of the coronoid fragment determines the stability of the joint. A diminution of the arch of the incisura semilunaris by about 30 degrees causes instability of the elbow. We present an alternative way of treating the special case of a fracture of the coronoid process combined with comminuted fracture of the proximal end of the radius. A suitable fragment of the head of the radius is used to reconstruct the coronoid process. The stability achieved allows early functional postoperative treatment with a good range of movement at the elbow joint. PMID- 1876858 TI - [Femoral head preserving therapy in medial femoral neck fractures. A clinical study of the effects of treatment method on the outcome]. AB - The main problem with fractures of the femoral neck is the high incidence of avascular necrosis and non-union. While the rate of pseudarthroses has been lowered by treatment with stable compression screws, no effect of this technique on the incidence of head necrosis is evident. The reasons for this are rupture of vessels, wide dislocation of fragments and diminution of blood supply owing to intracapsular hematoma. Since 1982 we have been using a defined indications and therapy schedule for these fractures, which is based on the main principle of open operative treatment in younger patients. This procedure is the only one that makes accurate reduction and stable internal fixation of fragments possible. With the opening of the capsule and evacuation of the hematoma pressure on the blood vessels is relieved. The analysis of data recorded in 81 patients treated with open reduction and stable internal fixation revealed that poor functional results and avascular necrosis occur especially in fractures of Garden's stages III and IV that are operated on longer than 6 h after the trauma is sustained. Therefore, the operation should be performed as soon as possible as an emergency procedure to reduce the likelihood of such severe complications. PMID- 1876859 TI - Fanconi anemia: constitutional aplastic anemia. PMID- 1876860 TI - Introduction: the molecular biology of hematopoiesis. PMID- 1876861 TI - Regulation of primitive human hematopoietic cells in long-term marrow culture. PMID- 1876862 TI - Stroma-cell dependent hematopoiesis. PMID- 1876863 TI - Transcription factor regulation of hematopoietic lineage cells. PMID- 1876864 TI - Retroviral-mediated gene transfer of human adenosine deaminase into murine hematopoietic cells. PMID- 1876865 TI - Mixed cryoglobulinemia cross-reactive idiotypes: implications for the relationship of MC to rheumatic and lymphoproliferative diseases. PMID- 1876866 TI - Bloom syndrome and ataxia telangiectasia. PMID- 1876867 TI - The role of proteoglycans in cervical dilatation. PMID- 1876868 TI - Cervical distensibility changes in pregnancy, term, and preterm labor. PMID- 1876869 TI - Ultrasound: a new approach to the evaluation of cervical ripening. PMID- 1876870 TI - Cervical mucus and sperm transport in reproduction. PMID- 1876871 TI - Incompetent cervix: pathogenesis, diagnosis and treatment. AB - The incompetent cervix is a diagnostic dilemma. There are no well-defined or strict criteria to diagnose cervical incompetence, and therefore the indications for treatment are not always clear. Forty years ago, when the basic methods of treatment were first described, the diagnosis seemed relatively simple and the treatment acceptable. There have been very few large, prospective, randomized, well-controlled studies to determine the efficacy of the various surgical methods. Liberal use of cerclage procedures in situations of moderate risk for premature delivery or as prophylactic measures in multiple pregnancy does not appear to improve outcome as judged by prematurity or fetal survival. At the present, fetal survival cannot be a measure of the success of a surgical procedure because so many other factors play a role in outcome, such as the quality of obstetrical and neonatal care. Therefore, outcome of surgical procedures should be judged by more objective criteria, such as prolongation of pregnancy (in weeks) and birth weight. The methods that would allow making an unequivocal and objective diagnosis of incompetent cervix are not yet available. Until we reach this goal, the subject of cervical incompetence and effectiveness of its treatment will remain challenging and elusive. PMID- 1876872 TI - Pharmacological modulation of cervical compliance in the first and second trimesters of pregnancy. PMID- 1876873 TI - Use of prostaglandins for induction of labor. PMID- 1876874 TI - The physiology of the uterine cervix in reproduction. PMID- 1876875 TI - The physiology of the uterine cervix in reproduction. Introduction. PMID- 1876876 TI - Relationship between myometrial and cervical functions in pregnancy and labor. PMID- 1876877 TI - Tropical pulmonary eosinophilia. PMID- 1876878 TI - The lazy eye. PMID- 1876879 TI - Correlation of lower respiratory tract inflammation with changes in lung function and chest roentgenograms in patients with untreated tropical pulmonary eosinophilia. AB - Forty-one patients with untreated tropical pulmonary eosinophilia (TPE) were studied to determine whether there was any relationship between lower respiratory tract inflammation and either changes in lung function or abnormalities in chest roentgenograms. Total number of inflammatory cells in bronchoalveolar lavage (BAL) fluid, consisting of alveolar macrophages, lymphocytes, eosinophils and neutrophils had significant negative correlations with transfer factor (TLCO) (r = 0.519, p less than 0.001), transfer coefficient (KCO) (r = 0.312, p less than 0.05) and total lung capacity (TLC) (r = 0.352, p less than 0.05). The absolute count of eosinophils in BAL fluid had a significant negative correlation with TLCO (r = 0.430, p less than 0.01) and KCO (r = 0.300, p = 0.05), but not with forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) or TLC. However, the absolute count of alveolar macrophages had a significant negative correlation with FVC (r = 0.343, p less than 0.05), FEV1 (r = 0.341, p less than 0.05) and TLC (r = 0.305, p less than 0.05), but not with TLCO or KCO. The total number of lymphocytes had a negative correlation with TLC (r = 0.315, p less than 0.05). There was no correlation between the types of cells recovered in BAL fluid and changes in chest radiographs as assessed by the ILO classification for occupational lung diseases. These data suggest that there may be a dissociation of pulmonary pathophysiological changes produced by different inflammatory cells in the lower respiratory tract. Macrophages and lymphocytes may produce more harm to the lung, as evidenced by significant negative correlations of these cells with lung volumes. PMID- 1876880 TI - A study of amblyopia in 18-19 year old males. AB - During a vision screening of 6,556 National Service pre-enlistees aged 18-19 years at the Medical Classification Centre of Central Manpower Base, 48 subjects were found to have visual acuity of 6/12 or less in one or both eyes in the absence of ocular pathology. The prevalence of amblyopia in this population is 0.73%. Amblyopia was due to anisometropia in 24 cases (50%), strabismus in 9 cases (18.7%), high astigmatism (meridional) in 7 cases (14.5%) and other causes or a combination of factors in 8 cases (16.7%). Strabismic amblyopia is most commonly associated with esotropia. There is a positive association between the severity of amblyopia and the degree of strabismus in strabismic amblyopes. Meridional amblyopia tends to be less severe than most other types of amblyopia. The amblyopes were detected late (average 7-10 years of age) and orthoptic treatment of a small minority of them upon diagnosis was unsuccessful. PMID- 1876881 TI - Mortality among psychiatric inpatients in Singapore. AB - This study examines the Standardized Mortality Ratio (SMR) by age, sex and cause of death among psychiatric inpatients in Singapore. Mortality in mentally ill inpatients was found to be 2.79 times that of the general population. The SMR decreased with age and the SMR for those 70 years and above was lower than that reported in the literature. The mortality ratio was most accentuated in the younger patients, especially in the female. Excess mortality was observed in both the natural as well as the unnatural causes of death. Among the natural causes of death, infection and pneumonia showed high excess in mortality. In the unnatural causes of death, suicide was predominant. PMID- 1876882 TI - Maintenance haemodialysis in Singapore. AB - The chronic haemodialysis programme of the Singapore General Hospital started in 1968 as a hospital-based fully nurse-assisted programme. This has since expanded to include Self Dialysis and Home Dialysis programmes. Data of 425 patients who entered the dialysis programmes was analysed retrospectively. The major cause of end stage renal failure was chronic glomerulonephritis (52%). Almost half of the patients in the haemodialysis programme were patients on self-dialysis (49%). There were 157 withdrawals and 116 deaths. Survival has improved tremendously with the use of treated water for dialysis from 1981. The 5 year survival in an earlier group of patients dialysed with untreated water was 48% compared with 81% in a late group dialysed with treated water (p less than 0.001). The pattern of complications has also changed with a lower incidence of dialysis osteomalacia, hypertension, hepatitis and eradication of dialysis dementia. PMID- 1876883 TI - Validation of the General Health Questionnaire in female video display unit (VDU) operators in Singapore. AB - Fifty-seven Chinese female Video Display Unit operators employed in a multi national company were asked to complete the 28-item General Health Questionnaire (GHQ-28). This is part of a study on stress and asthenopia in this group of workers. Validity of the GHQ-28 was determined by comparison with the Clinical Interview Schedule (CIS). The GHQ-28 was found to give optimum results with a cut off score of 5/6. The CIS classified 28.07% as cases and this was comparable to the estimated prevalence of 28.03% derived from the GHQ. PMID- 1876884 TI - Cigarette smoking among school children in Singapore. Part II--Development of the smoking habit. AB - The second in this series on smoking among school children in Singapore aims to define the characteristics of young smokers. Results show that of respondents who had ever smoked, the median age of experimentation with smoking was 12 years. This was seen among boys as well as girls. The median age at which current smokers went on to smoke regularly was 14 years, approximately two years after trying their first cigarette. Friends and parents were the main sources of the first cigarette for all categories of smokers, whether they be ex smokers, experimenters or current smokers. Among the reasons as to why current smokers smoked, the leading two were "to relax" (46.4%) and "out of sheer curiosity" (22.3%). Boys tend more to smoke with friends of the same sex (40.6%) whilst girls preferred mixed company (45.5%) when they smoked. Fathers played a major role in the development and continuation of smoking among those who had ever smoked before--52.0% of boys and 51.6% of girls currently smoking reported that their fathers smoked as well. PMID- 1876885 TI - Ureterorenoscopy: factors influencing success. AB - The first 100 patients with ureteric calculi to undergo planned ureteroscopy and lithotripsy were retrospectively studied to evaluate the factors which influenced the success of the procedure. All 75 males and 25 females who underwent this procedure had surgical indications to treat the stones. The factors influencing a successful outcome were studied over four different time frames. It was found that the procedure was more successful in females, and lower ureteric stones. The stone size did not affect the outcome as expected. The learning curve was very evident as increased experience produced higher success rates for ureteric access and lithotripsy, less morbidity, shorter operating time and lower open surgery rates. The introduction of the miniscope and laser lithotripsy was however the most significant factor in ensuring a successful outcome. PMID- 1876886 TI - The anatomy of the Fossa of Rosenmuller--its possible influence on the detection of occult nasopharyngeal carcinoma. AB - The Fossa of Rosenmuller (FOR) is a well established site of origin of nasopharyngeal carcinoma (NPC). Detection of early NPC requires a sound knowledge of the anatomy of the FOR. The authors study the anatomy of the FOR with the aid of CT Scan and discuss the possible influence of the anatomy of the FOR on the detection of occult NPC. This paper reveals that there are cases of postnasal space which cannot be fully inspected clinically due to the peculiar anatomy of the FOR. PMID- 1876887 TI - The diagnostic yield of upper gastrointestinal endoscopy in the investigation of anaemia. AB - Computer records of patients endoscoped over a 34-month period were studied to assess the diagnostic yield of gastrointestinal endoscopy in patients with anaemia. Patients with obvious gastrointestinal bleeding and known gastrointestinal pathology were excluded. On hundred and thirty-six patients were endoscoped for anaemia. Eighty-three of them (61%) had iron deficiency anaemia and 53 (39%) had other types of anaemia. The ages of the patients with iron deficiency anaemia (mean 56 years) were significantly lower than those of other anaemias (means 65 years), (p less than 0.003). Patient characteristics were otherwise comparable. There were significant endoscopic findings (ulcers, carcinoma and haemorrhagic or erosive gastritis) in 26 of 83 patients (31%) with iron deficiency anaemia, in 11 of 53 patients with other anaemias (21%) and 37 of 136 patients (27%) combined. Significant endoscopic findings were found in 506 of 2224 patients (23%) endoscoped during this period who were not anaemic, did not have obvious gastrointestinal haemorrhage and were not known to have gastrointestinal diseases. The diagnostic yield for iron deficiency anaemia was significantly higher than for the non anaemic group (p less than 0.05). There was no difference between the diagnostic yields of iron deficiency and other anaemias, other anaemias and the non anaemic group, or total anaemias and the non anaemic group. Gastrointestinal symptoms and history of analgesic or steroid usage did not appear to increase the incidence of gastrointestinal lesions in either iron deficiency anaemia or other anaemias. Twenty-three of 41 patients (56%) who had no cause for anaemia found at the end of all investigations were colonscoped.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1876888 TI - Shivering during regional anaesthesia and its control with pethidine. AB - Ninety-seven consecutive patients who underwent four different types of regional anaesthesia such as lumbar epidural, spinal, caudal and brachial blocks were studied for their incidence of shivering. Fifty percent of patients who received epidural anaesthesia shivered compared to 19% of patients who received either spinal or caudal anaesthesia. None of the patients who had brachial block shivered. Intravenous injection of 25 mg pethidine would stop shivering in almost all patients who shivered during regional blocks. PMID- 1876889 TI - Comparison between flowcytometry and immunoperoxidase staining for the enumeration of lymphocyte subsets. AB - Immunoperoxidase staining was compared with flowcytometry for the enumeration of lymphocyte subsets. The percentages obtained for peripheral blood lymphocytes using immunoperoxidase (CD3 = 76 CD4 = 27.9, B = 10.7 CD4/CD8 = 1.8) differed significantly from those obtained by flowcytometry (CD3 = 65.7 CD4 = 39.4, CD8 = 25.6, B = 16.7, HLA DR = 11.9 CD4/CD8 = 1.54) for certain subsets (CD3, CD4, B). There was no significant difference in lymphocyte subsets between children and adults using the same method. These differences are probably due to the different methods used to prepare lymphocytes for analysis. Other factors that should also be considered are the presence of CD4 antigen on monocytes and CD8 on natural killer cells. PMID- 1876890 TI - The outcome of patients with acute bronchial asthma presenting to the emergency room. AB - We collected data on patients above the age of 5 years with acute bronchial asthma who presented to the emergency room of Hospital Sains Universiti Sains Malaysia during the period between 1 January to 31 March 1990. Two hundred and twelve patients (57% males and 43% females) who made a total of 271 visits were recorded. This constitutes 16.3% of all adults and paediatric medical cases seen in the emergency room during this period. The majority of patients presented between 8 pm and 6 am which contrasts with the attendance pattern due to other causes. We also recorded two peak periods of presentation (between 8 pm and 12 midnight and between 6 am and 10 am). Thirty-one (11.4%) cases resulted in admission. Of the 240 cases that were successfully treated and discharged from the emergency room, there were 59 relapses (in 45 patients). Twenty-two percent of the relapses occurred within 24 hours of the last visits. We recorded lower rates of admission as well as relapses compared to all previous studies. Our finding of bimodal pattern of presentations was also not previously reported. PMID- 1876891 TI - Life-threatening arrhythmias after intravenous lidocaine alone or with magnesium in myocardial infarction complicated by ventricular fibrillation. AB - To compare the effects of Lidocaine (LID) alone or with Magnesium Sulfate (M) on life-threatening ventricular arrhythmias which followed cardioverted prolonged ventricular fibrillation (VF) during an acute myocardial infarction (AMI), we studied 34 (24.63%) out of 138 patients aged from 52 to 83 years (mean: 66.92 + 8.82) with an anterior AMI, who had cardioverted prolonged VF. Twenty patients (58.8%)--Group A--received LID 2 mg/min at constant-rate infusion through a subclavian catheter following a bolus of LID 100 mg, whereas 14 patients (14.2%)- Group B--received LID at the same dose + M 2.5 mg/min. All the patients had continuous monitoring and LID serum level was measured daily by means of immunofluorescent method (TDX Abbot; range 1.5-5 micrograms/ml). Group A had the following mean serum levels of LID; 250 + 0.9; 1.52; 245 +/- 0.9; 3.20 + 1.1. Group B showed: 2.65 + 1.2; 2.80 + 1.8; 3.10 + 1.2; 3.25 + 1.1. Continuous monitoring displayed the following arrhythmias respectively for Group A and Group B: VT 37 times vs 16(P less than 0.05, significant), transiently cardioverted VF during therapy 17 times vs 6(p less than 0.01, significant), 8 deaths from VF vs 6 - 3 from VF and 3 from asystole - (p = NS). LID + M treatment seemed to be more effective than LID alone to reduce life-threatening arrhythmias following cardioverted prolonged VF of AMI but not the deaths. In addition, M would raise moderately LID serum level and this fact, not yet well known, needs further investigation. PMID- 1876892 TI - Drugs and the elderly. AB - Prescribing for the older individual requires a great deal of thought. Multiple pathology is usually associated with multiple drug taking and therefore a high risk of adverse drug reactions. Physiological changes have important bearing on drug usage. Constant vigilance is required to ensure safe prescribing. PMID- 1876893 TI - Parkinson's disease. AB - The management of the elderly patient with idiopathic Parkinson's disease requires great attention to detail. Treatment should only be considered when the daily activities of life are affected. Medication should be commenced cautiously. Regular review is essential and co-ordination with other members of the multidisciplinary team is vital. PMID- 1876894 TI - Infections in the elderly. AB - Infections are a leading cause of morbidity and mortality in the elderly. Altered host defences, a senescent immune system, chronic illnesses, and environmental factors all contribute to the aged's predisposition to infection. Infections can present in atypical fashion contributing to diagnostic and therapeutic delays. Awareness of altered antibiotic absorption, metabolism, and excretion in the elderly is essential to correct antibiotic selection and dosing. Additionally, antibiotic interactions with medications commonly used to treat chronic illnesses should be taken into consideration prior to antibiotic prescribing. Prevention of infectious complications in the elderly requires interest, education, vaccination, and early intervention. PMID- 1876895 TI - Pericardial mesothelioma presenting as a mediastinal mass. AB - A case of malignant mesothelioma of the pericardium, who presented with an anterior mediastinal mass, is reported. Such a presentation of the pericardial mesothelioma is distinctly rare. As in most of the other reported cases, our patient also did not have any exposure to asbestos. The diagnosis in the present case was established after surgery. Most of the cases reported in the literature, were diagnosed only at postmortem. The treatment of choice is surgical resection of the tumour. The prognosis of pericardial mesothelioma is poor and till now, only two long survivals have been reported. PMID- 1876896 TI - Vaginal vault prolapse--a case report. AB - Vaginal vault prolapse after hysterectomy is a distressing complication for both the patient and the surgeon. Successful repair of post-hysterectomy vault prolapse is one of the most difficult problems in gynaecological surgery. The aim of the surgery should be to restore coital function and cure the prolapse permanently. PMID- 1876897 TI - Drug interaction between cyclosporine A and quinine in a renal transplant patient with malaria. AB - We report a previously undocumented drug interaction between cyclosporine A and quinine. A 39 year old Asian with a recent renal transplant was diagnosed to have a mild cerebral falciparum malaria. He was treated with seven days of oral quinine (600 mg, 8 hourly), followed by a stat dose of pyrimethamine (75 mg)- sulfadoxime (1200mg) because of a strong suspicion of chloroquine resistant falciparum malaria. Using a polyclonal radioimmunoassay method, we measured morning trough cyclosporine A level before, during and after the quinine treatment. Results showed a gradual decrease in the cyclosporine A level from a baseline value of 328 ng/ml to 107 ng/ml after seven days of oral quinine with a subsequent rise to pre-treatment level after discontinuation of quinine. There was no significant change in the dose of cyclosporine A administered during the period of quinine treatment (4.05 to 3.83 mg/kg body weight). Biochemical liver function tests, serum creatinine and hematological parameters were also essentially unchanged during this period. In vitro study showed no significant methodological interference in the cyclosporine assay by quinine dihydrochloride. These findings suggest an in vivo drug interaction between cyclosporine A and quinine. The mechanism of this interaction is not clear. Further studies are required to confirm the significance of this observation. Quinine and its stereoisomer, quinidine should be used with caution until further information is available. PMID- 1876898 TI - [Results of a questionnaire survey of physicians on issues of medical occupational expertise]. AB - Results of questionnaire survey of 275 physicians of major clinical specialties are provided in regard to 26 aspects of medical expertise. Information is provided which characterise physicians' knowledge of medical expertise provisions, the sources of this knowledge, the assessment of competence of this expert commission and of its director, ungrounded issue of sick lists, denial to identify factual disability, causes leading to this phenomenon and also ways of reducing the level of morbidity associated with temporary disability. PMID- 1876899 TI - [Mortality trends of Krasnoyarsk Region population from oncological diseases]. AB - An increasing general trend in aging of population during the last decade stipulates the necessity to conduct a comparison (both in time and territory aspect) of either age-specific health indices or their standard variants because without age peculiarities of population during different years the results might be misrepresented. The data acquired in the course of the present study indicate that oncological morbidity of population in the Krasnoyarsk region in the majority of age and social groups (urban and rural inhabitants) not only have not increased but even dropped in 1989 as compared with 1959. One should be careful in assessing general indices of population health along with obligatory use of methods permitting to take into account the demographic peculiarities of population in the years compared. PMID- 1876900 TI - [Methods of assessing the state of the digestive system in mass examinations of rural population]. AB - On the basis of physician's logic a questionnaire has been elaborated for identifying the most common diseases of digestive system during mass medical check-ups of rural population. 98 combinations of signs were considered in the diagnostic algorithm for making conclusions regarding 11 diseases. The programme elaborated envisages recommendations on the volume of examinations necessary for verification of diagnoses. The questionnaire and rules governing it were verified for 152 patients. By means of mathematical statistics methods the informativeness of the signs used have been assessed. The analysis showed a great diagnostic value of choosing signs on the basis of physician's logic taking into account their pathogenetic correlation. The efficiency of questionnaires have been demonstrated and sufficient under conditions of automated examinations sensitivity (on the average for diseases 78.1%) and specificity (on the average for diseases 70.0%). PMID- 1876901 TI - [Use of the standardization principle in public health institutions]. PMID- 1876902 TI - [Development of rural clinics system under conditions of restructuring of Soviet public health]. PMID- 1876903 TI - [Experience in organizing competition of school health education teams]. AB - One of the main tasks of Soviet medicine--the healthy lifestyle formation among population can be accomplished with the help of school health education teams. The training of school health education teams is one of the forms of out-of school hours activities in hygienic education and training of pupils and can easily be accomplished through organizational plans of activities at any school or industrial training school. The organization of school health education teams should unite the efforts of teachers, specialists from the service of healthy lifestyle formation, cultural institutions, young communist league and youth organizations and other departments and public agencies concerned. Using various active publicity media school health education teams should become active healthy lifestyle promotion organizations and their performance can be conducted before any audiences. The working experience of school health education teams is in need of investigation, improvement and dissemination. PMID- 1876904 TI - [Qualification characteristics of specialists--graduates of medical and pharmaceutical institutes]. AB - The development of medical education is associated with scientific elaboration of a system of periodically renewed requirements for specialists training quality, introduction of new methods and means for objective assessment of their professional competence. The present dectarative, non-constructive and non classifying nature of qualification characteristics for graduates of medical and pharmaceutical institutes necessitated the carrying out of investigations aimed at the elaboration of a new system of qualification characteristics capable to fulfill the function of scientifically substantiated quality standards of higher medical education for every specialty. The paper describes the evolution of methodological approaches to the making of these documents, considers their new structural peculiarities, provides the technology of their projecting, determines their place in the target system of continuous medical education. The major peculiarity of a new system of qualification characteristics is the adequacy of targets to the requirements for the performance of specialists in applied public health, the possibility of estimating or evaluating the achievement of targets, the possibility of projecting these targets with the help of through programmes of specialties in the educational process by their specification in intermediate targets of training which are the basis for improving the system of training at all stages. The authors analyse the international experience and outline the prospects for the use of new ideas in future work on qualification characteristics. Recommendations are made to use the proposed methodology for correcting qualification characteristics in the system of secondary medical education and in the system of postgraduate training of physicians and pharmacists. PMID- 1876905 TI - [Teaching social hygiene and public health administration]. PMID- 1876906 TI - [Pioneers of zemskaia medicine: N. A. Dolgorukov]. PMID- 1876907 TI - [Assessment of the old as a cumulation of the outdated and the current in the study of history of neurology in the 19th and early 20th centuries]. PMID- 1876908 TI - [Public health and medical sciences of Bukovina during 50 years of Soviet rule]. PMID- 1876909 TI - [Clinico-morphological characteristics of dilated cardiomyopathy]. AB - The paper presents the results of a clinicomorphological study of 50 patients with dilated cardiomyopathy. ECG, echocardiography, x-ray revealed atrial fibrillation, parasystole, extrasystole, impairment of intraventricular conduction, symptoms of a focal cicatricial myocardial lesion, high end-systolic and end-diastolic volumes, reduced ejection fraction, marked axial dilatation of the heart. Morphologic evaluation showed diffuse and diffuse microfocal cardiosclerosis, combination of sites of hypertrophic myocardiocytes with dystrophic foci, atrophy, sclerosis. Morphological evidence is available for arrhythmic, cardiomegalic, aneurysmic, infarction-like and pseudovalvular dilated cardiomyopathy. PMID- 1876910 TI - [Psychoemotional condition and autonomic nervous system in patients suffering from myocardial infarction in the young age]. AB - The analysis of clinical pattern, psychovegetative disturbances and metabolic defects in coronary patients with a history of myocardial infarction at young age provided information for recognition of two subgroups: normal-weight and overweight patients. Metabolic derangement manifesting with high total cholesterol and triglycerides levels occurred in group II whereas dystonia was registered in both groups as shown by assessment of reactivity and vegetative tone. Background parasympathetic activation and sympathoadrenal activation in exercise grew. Overweight patients seemed to have a marked vegetative dysfunction. The two patterns established have both theoretical and practical significance in terms of design of therapeutical measures. PMID- 1876911 TI - [Pathogenesis of homeometric and heterometric autoregulation of the heart in mitral valve defects]. AB - Right ventricular (RV) function was investigated using rheopulmonography at Valsalva's manoeuvre and echocardiography in 36 patients with rheumatic heart disease which were divided into three groups: with RV normal-size chamber and normal thickness of the wall (I), with normal-size RV chamber and myocardial hypertrophy (II), with RV dilatation and hypertrophy. In patients of group I there appeared mitral stenosis of degree I (Gorlin) and insignificant elevation of pressure in the pulmonary artery. Mitral defect was compensated through the mechanism "stress-mobilization" underlying homeometric autoregulation of the heart. As a result, muscular thickness grows without hypertrophy and becomes stronger. In more pronounced narrowing of mitral opening (group II) the second stage of the compensation comes: in latent pulmonary hypertension hypertrophy develops as a prolonged adaptation to greater load. Hypertrophic myocardium is the most resistant to overloading with external pressure. In group III patients with mitral narrowing degree 2 and more distinct pulmonary hypertension one can observe an addition of Frank--Starling mechanism--heterometric type of autoregulation. In spite of its triggering compensation of the defect remains insufficient (circulation deficiency becomes clear-cut in patients of group III). PMID- 1876912 TI - [Hypokininemia in chronic bronchitis caused by cotton dust]. AB - Examination of 102 patients who developed bronchitis due to exposure to cotton dust running a complicated or noncomplicated course recognized a moderate hyperkininemia in 40% of cases (4.46 +/- 0.43 against the normal 2.90 +/- 0.42) and apparent hypokininemia in 60-63% of cases (0.52 +/- 0.03 against 2.90 +/- 0.42). Hypokininemia appeared in association with pathological shifts in external respiration and central hemodynamics. It is an unfavourable factor contributing to formation of occupation complications of chronic bronchitis: pulmonary emphysema, pulmonary hypertension and cor pulmonale. PMID- 1876913 TI - [Two-dimensional pulse Doppler echography in chronic hepatitis]. AB - A separate estimation of blood flow in the portal and hepatic veins using ultrasonic two-dimensional tomography and impulse Doppler echography of the liver was tried in 30 chronic sufferers with hepatitis versus 31 healthy controls. Two dimensional impulse Doppler echography recorded the blood flow spectrum in the right hepatic vein at the site of its entering of vena cava inferior as well as in the portal vein at the portal fissure simultaneously with ECG. The index of portal blood flow and that of right hepatic vein flow in systole are proposed. The above method warrants a separate estimation of hepatic circulation in hepatic pathology whereas its combination with ultrasonic tomography increases its diagnostic potential at early stages of hepatic impairment. The analysis of the central and hepatic hemodynamics established hepatic circulation participation in regulation of central hemodynamics. PMID- 1876914 TI - [HBO in the combined therapy of purulent peritonitis and peritoneal sepsis]. AB - The study was made of HBO effect on changes of biologic fluid toxicity in purulent peritonitis. HBO was introduced in combined therapy of 68 patients (32 with general peritonitis and 36 with peritoneal sepsis). Lethality in peritonitis patients reached 40.6% (19 patients), in sepsis patients 33.3% (12 patients). PMID- 1876915 TI - [Insulin effect on lipidemia and immunological indices in diabetes mellitus type 1]. AB - Biochemical and immunologic studies were carried out in 361 patients with diabetes mellitus type I treated with large nonphysiological doses of insulin and physiological ones. Atherosclerosis and noticeable changes in lipid serum spectrum, immunity derangement occurred significantly more often in heparin overtreatment suggesting a conclusion on a possible role of chronic insulin overdosing in mechanisms of atherosclerosis development in diabetics. PMID- 1876916 TI - [Clinical manifestations, diagnosis and treatment of anaerobic non-clostridium infections]. PMID- 1876917 TI - [Microcirculation and capillary permeability during hemodialysis in patients with renal insufficiency]. AB - Time course changes in microcirculation (MC) and capillary permeability (CP) were investigated in 191 patients with acute renal failure (ARF) and 45 patients with terminal chronic renal failure (CRF). Similar in type MC and CP disturbances were found in all CRF and oligoanuria ARF patients. These were more pronounced in CRF sufferers depending in degree on the disease severity. Knizeli's phenomenon ranged from 2.2.KII to 3.3.KIII. The total conjunctival index reached 22.99-25.20 in CRF and 19.4 in ARF. Unlike ARF patients, those with CRF had no positive trend in MC and CP. A transient change for the better came after hemodialysis and was seen in occasional patients. It is suggested that no response to hemodialysis is indicative of CRF and ARF poor prognosis. The trend in MC can help in prognostication of CRF development in acute cases. PMID- 1876918 TI - [Hyperbaric oxygenation in the treatment of compression mononeuropathies]. AB - 105 patients with compression mononeuropathies were divided into 2 groups by duration of HBO performed under an original method. The effect of HBO treatment was assessed by changes in neurological symptoms and positive trend on ENMG. The most appreciable response was obtained in acute disease treated by 4-session short course. Longer courses of VIII-X sessions were less efficient. PMID- 1876919 TI - [Radiodiagnosis of metastases to the upper abdominal and retroperitoneal lymph nodes]. AB - The examination of 170 patients with cancer of the esophagus and proximal stomach made it possible to specify x-ray, ultrasonic and CT signs of cancer metastases to the upper abdomen and retroperitoneum. A scheme of radiodiagnosis of these metastases is suggested. The diagnostic value of x-ray, echography and CT was considered in relation to various lymph nodes involvement. PMID- 1876921 TI - [Differential diagnosis of coma in the therapeutic practice]. PMID- 1876920 TI - [Neocytapheresis in donors]. AB - Various techniques and blood separators were employed to obtain therapeutic doses of immature erythrocytes (neocytes) from blood of 18 donors. Regimens of neocyte apheresis, preparative efficiency of blood separators, morphofunctional and biophysical characteristics of neocytes obtained were compared. Neocyte apheresis shows promise for hematological patients dependent on red cells transfusion. PMID- 1876922 TI - [Treatment of ascites in liver cirrhosis]. PMID- 1876923 TI - [Prenatal ultrasonic diagnosis of a single heart ventricle]. PMID- 1876924 TI - [Psychological characteristics of patients with borderline arterial hypertension and prophylaxis of cardiovascular diseases]. PMID- 1876925 TI - [Antithrombogenic characteristics of vascular wall and intravascular thrombocyte activation in atherosclerosis of peripheral arteries]. PMID- 1876926 TI - [ATP therapy in paroxysmal supraventricular tachycardias during emergency care]. PMID- 1876927 TI - [Clinico-electromyographic examination of patients with chronic atypical lung diseases]. PMID- 1876928 TI - [Obligate anaerobic non-sporulating microflora in pleural empyema]. PMID- 1876929 TI - [Complications of duodenal ulcer in young patients]. PMID- 1876930 TI - [Alimentary correction of alcoholic liver diseases]. PMID- 1876931 TI - [Atropine test for the choice of surgical methods in duodenal ulcer]. PMID- 1876932 TI - [Early active detection of proctologic diseases using a system of step-by-step automated screening]. PMID- 1876933 TI - [Biochemical criteria of endogenous intoxication in large intestine diseases]. PMID- 1876934 TI - [Parathyroid gland cysts and primary hyperparathyroidism]. PMID- 1876935 TI - [Treatment of complicated transverse colon diverticulosis by prolonged retroperitoneal novocaine blockade]. PMID- 1876936 TI - [A course and outcome of chronic hepatitis with the presence of serum markers of replication phase of hepatitis B virus]. PMID- 1876937 TI - [Effect of social, genetic and personality factors on the outcome of iron deficiency anemia and their role in the disease prognosis]. PMID- 1876938 TI - [Computerized tomography in the diagnosis of heart neoplasms]. AB - Computed tomography (CT) was used to study 56 and 4 patients with primary and secondary cardiac blastomas, respectively. CT allows differentiation between a racemose and dense endocardial tumor, localization of myxoma pedicle, recording its prolapse into the adjacent chamber, identification of extra-, intracardiac and intramyocardial tumor growth as well as changes in adjacent vessels. CT image of cardiac myxoma is similar to a filling defect of diminished density, that of extra-endocardial tumors display polymorphism. Blastomatous invasion of the heart is characterized by blurring of cardiovascular elements boundaries, pericardial thickening and fluid accumulation. CT is advocated as a new, noninvasive and highly efficient diagnostic modality in cardiac tumors. PMID- 1876939 TI - [Epidural analgesia in the surgical treatment of patients with diabetes mellitus]. PMID- 1876940 TI - [Urgent cerebral pathology in hypophyseal nanism]. PMID- 1876941 TI - [Laser reflexotherapy in osteoarthrosis deformans and rheumatoid arthritis]. PMID- 1876942 TI - [Clinical and laboratory evaluation of ciprofloxacin effectiveness]. PMID- 1876943 TI - [Food poisoning , complicated by infectious-toxic shock and acute stomach dilatation]. PMID- 1876944 TI - Health service improvisation or resource distribution? PMID- 1876945 TI - Some research achievements at the University of Natal Medical School, 1951-1991. PMID- 1876946 TI - Attitudes to organ donation. PMID- 1876947 TI - Breast cancer--all the breakthroughs since lunchtime. PMID- 1876948 TI - Calling the AIDS shots at Wits--'guidelines on HIV infection and AIDS'. PMID- 1876949 TI - The renal histopathology of essential malignant hypertension in black South Africans. AB - The renal histopathology of essential malignant phase hypertension in two groups of black South Africans was studied. The first, an autopsy series, consisted of material obtained in 1956-1961, a period when adequate antihypertensive therapy had not yet become generally available. The second group, a renal biopsy series, was from an era when effective antihypertensive therapy was available (1979 1989). The study showed that the clinical and histopathological changes of malignant hypertension were similar in both the pre-treatment and treatment eras. Fibrinoid necrosis was found in 92% of the autopsy sections and 44% of the biopsies. While mucinous, onion-skin and fibrotic changes of the blood vessels were commonly found, they were not invariably present and could not be considered the histopathological hallmark of malignant nephrosclerosis. It was often impossible on histological examination to distinguish malignant nephrosclerosis arising de novo from that superimposed on long-standing previous benign hypertension. Replication of internal elastic lamina, which has been considered a marker of long-standing previous benign hypertension, was a nonspecific finding and was frequently observed in young hypertensive subjects with a short clinical history. When fibrinoid necrosis is present, diagnosis of malignant nephrosclerosis can be made with confidence in black South Africans. PMID- 1876950 TI - Significant cost-saving with modification of antihypertensive therapy. AB - Thirty patients attending Somerset Hospital Outpatient Department, Cape Town, who were on nifedipine for hypertension or chest pain, were followed up for 6 months after alternative therapy was instituted. After the change of treatment, blood pressure control improved and no serious side-effects were encountered. Reserpine combined with a thiazide was a major component of the new regimen which reduced the monthly cost per patient from R54 to R14, a saving of 73%. If this saving was extended to 5% of the potential hypertensive patients in the RSA it would amount to R8 million per month. Although a self-assessment depression inventory was completed by 21 patients, our study does not fully evaluate the impact on quality of life. The likelihood of side-effects is, however, small--provided that the maximum daily dose of reserpine does not exceed 0.1 mg. We feel that a more considered approach is needed in the choice of antihypertensive agents. PMID- 1876951 TI - Assessing operability in squamous carcinoma of the oesophagus. Are pre-operative investigations unreliable? AB - Pre-operative investigations, although providing useful information, were unreliable in predicting resectability in patients with malignant oesophageal lesions. Chest radiographs excluded metastasis and active tuberculosis. The barium swallow examination determined the length of the lesion and displayed various displacements, none of which excluded resectability. Tumour infiltration of the airways was the only change visible at bronchoscopy that contraindicated resection. Computed axial tomography was unreliable in excluding extra oesophageal tumour extension and operability. As all these pre-operative investigations have their limitations in assessing operability, exploration of the lesion is essential to determine resectability for squamous carcinoma of the oesophagus, provided there is prior histological confirmation of a malignant oesophageal lesion. PMID- 1876952 TI - Septic shock in the Intensive Care Unit, Hillbrow Hospital, Johannesburg. AB - The records of all patients with septic shock admitted to an intensive care unit during a 15-month period were analysed retrospectively. The main purpose of the study was to describe the aetiology and clinical features of illness, and to determine the outcome of the patients, including those factors influencing prognosis. Thirty-five patients (46% medical, 54% surgical) fulfilling the criteria for the diagnosis of septic shock were admitted to the study. There were 21 male and 14 female patients. Most infections were community-acquired (69%). The two most common sources of infection were the respiratory tract and abdomen. All patients required inotropic blood pressure support. Most patients (94%) were mechanically ventilated and 7 required dialysis. Organisms, sometimes multiple, were isolated in 18 patients. Fifty percent of the isolates (12 of 24) were Gram negative, 10 were Gram-positive and there were 2 associated Candida albicans bacteraemias. The overall mortality rate was 40%. There was no difference in outcome between community or hospital-acquired infections, infections with Gram positive or Gram-negative organisms, or in patients with differing sources of sepsis. Features associated with a poorer prognosis were older age and higher bilirubin value. PMID- 1876953 TI - Surgical management of multiple limb gangrene following dehydration in children. AB - Multiple limb gangrene and auto-amputation without arterial vascular occlusive disease is uncommon. Seven such paediatric patients were managed at King Edward VIII Hospital, Durban, during the 6-year period ending in 1989. The spectrum and degree of limb gangrene ranged from phalangeal necrosis to distal limb mummification affecting one or more limbs. The most affected child had gangrene and mummification of all limbs as well as gangrene of the ear lobes and the tip of the nose. The main associated factor was severe fluid loss--2 children had received herbal enemas, with resultant hypotension, hypoperfusion, hypernatraemia and acidosis, which, it is postulated, led to peripheral thrombosis and the ensuing gangrene. It is suggested that aggressive fluid therapy, including low molecular weight dextran and correction of the metabolic derangement, should form the main thrust of the therapeutic endeavour. Once gangrene is established, surgical debridement and rehabilitation is all that is possible. Using this procedure only 2 patients died in the acute resuscitation phase. PMID- 1876954 TI - Immunity to rabies after administration of prophylactic human diploid-cell vaccine. AB - The immune status to rabies of 14 volunteers was determined using the commercially available Trousse Platelia Rage (Diagnostics Pasteur) enzyme immunoassay test system. Twelve subjects were evaluated before and between 6 months and 60 months after prophylactic intramuscular (deltoid) administration of rabies human diploid-cell vaccine, while the effect of booster doses on a further 2 volunteers was evaluated over an 11-year period. Optical density values were converted to international units to allow correlation with World Health Organisation seroneutralisation references. Values of greater than or equal to 0.5 IU are considered protective. The results showed that most individuals were still immune 2 years after vaccination; there was a tendency for serum antibody levels to decrease over a 5-year post-vaccination period. Antibody levels rose sharply after booster immunisation, after which they decreased at a much slower rate. In general, results revealed that after the first booster, additional booster vaccinations at 5-yearly intervals would provide adequate prophylactic immunity. There was, however, much individual variation, which emphasises the need to evaluate each individual at regular and shorter intervals to determine the need for booster vaccine doses. The test method employed is economical and well suited to such evaluations. PMID- 1876955 TI - Plasma noradrenaline and adrenaline levels in eclampsia. A preliminary study. AB - Plasma noradrenaline and adrenaline levels were measured in 18 women with eclampsia and 20 normotensive pregnant women matched for age and parity. While plasma noradrenaline concentrations were not statistically different in the two groups, plasma adrenaline values were higher in patients with eclampsia. The increases in adrenaline levels, although significantly elevated, were thought to be more related to stresses, such as muscular activity associated with convulsions. This study suggests that the aetiology of hypertension in pregnancy is not related to sympathetic overactivity. PMID- 1876956 TI - Low prevalence of delta hepatitis virus infection among blacks in Natal. AB - The prevalence of delta hepatitis virus (DHV) infection among hepatitis B surface antigen (HBsAg)-positive black subjects in Natal was determined. A total of 172 subjects was tested for the presence of antibodies to DHV; all were HBsAg positive. They comprised three groups: 51 urban children identified in a community-based seroprevalence survey, 81 subjects identified during a family study, and 40 institutionalised children. None of the 172 subjects was positive for antibodies to DHV. Based on calculations using a binomial distribution of infection, there was a 95% probability that the prevalence of DHV infection was below 30/100,000 HBsAg-positive persons. While DHV infection was found to be rare among blacks in Natal, the risk of delta hepatitis becoming widespread is ever present, since the high incidence of hepatitis B virus infection in black children provides ample opportunity for the concomitant spread of DHV. PMID- 1876957 TI - Subcellular distribution of asialoglycoprotein receptor in liver regeneration. AB - Asialoglycoprotein (ASGP) receptor specific activity was determined directly using a radiolabelled ligand (asialoorosomucoid) binding assay in various fractions of rat liver cells before and 24 hours after two-thirds partial hepatectomy. The specific activity of ASGP receptor in the plasma membrane fraction was significantly reduced 24 hours after partial hepatectomy. In an attempt to identify a subgroup of receptor involved in intercellular recognition the calcium-dependent ASGP receptor was re-assayed after pre-incubation in ethylenediaminetetra-acetic acid. This revealed significant amounts of additional receptor in microsomal preparations but not in plasma membrane fractions. Cryptic receptor levels were not affected by partial hepatectomy. Plasma membrane-bound receptor was significantly decreased in regenerating liver. PMID- 1876958 TI - An inflatable birth canal dilator. A randomised pilot study. AB - An inflatable device designed to achieve controlled dilatation of the pelvic floor soft tissues before the second stage of labour in women with epidural analgesia was tested in a randomised pilot study. Assisted vaginal delivery was required in 4/14 primiparous women (29%) after use of the dilator, and 8/16 controls (50%). The concept of improving the efficiency of pelvic floor dilatation and reducing the trauma associated with childbirth was found to be worth pursuing, and potential improvements in the design of the dilator were identified. PMID- 1876959 TI - Non-ketotic hyperglycinaemia in a neonate. A case report. AB - Non-ketotic hyperglycinaemia was diagnosed in a newborn infant presenting with lethargy, apnoea, hiccoughs and myoclonic seizures. The typical findings of raised cerebrospinal fluid:plasma glycine ratio, a burst suppression pattern on electro-encephalography, hypodense areas seen on computed tomography and lack of acidosis, ketosis and serum organic acid abnormality confirmed the diagnosis. Prenatal diagnosis by investigating the glycine cleavage enzyme system from a chorionic villus sample is not yet available. PMID- 1876960 TI - Necrotising fasciitis after caesarean section--association with non-steroidal anti-inflammatory drugs. A report of 3 cases. AB - Three cases of necrotising fasciitis following caesarean section are described. Each patient had received non-steroidal anti-inflammatory drugs (NSAIDs) in the immediate postoperative period. While the association of necrotising fasciitis and the use of NSAIDs may be coincidental, the use of this group of drugs, which impair normal defence mechanisms, should be avoided if at all possible in the postpartum patient. PMID- 1876961 TI - Guidelines on HIV infection and AIDS--notes on the statement from Wits. PMID- 1876962 TI - Hunger striking. PMID- 1876963 TI - Fish oil supplementation and cardiovascular disease. PMID- 1876965 TI - Temple Fay, M.D. 1895-1963. PMID- 1876964 TI - [Critical evaluation of femoro-popliteal-crural in situ venous bypass- experiments on valve elimination and hemodynamics]. AB - In a retrospective study we compared the results of 96 reversed (group I) and of 45 in-situ (group II) femoropopliteal infragenual venous bypasses. All reconstructions were done without TEA of the connecting vessels and without pre-, intra- or postoperative in - or outflow manipulations. The outflow tract (state of the crural arteries) in both groups was similar (p = 0.1). The states of ischemia were different (more cases of limb threatening ischemia in group II, 0.001 less than p less than 0.005). In opposition to most publications the cumulative patency rates were statistically different (88.8%/68.4% after 3 months, 73.1%/25.4% after 2 years, p less than 0.005). Also limited function rates-exclusion of all cases with reocclusion within 3 months respectively all operations with severe faults in indication or technique of operation, showed worse results for the group II (p less than 0.05). Most early reocclusions of in situ-bypass were caused by leaks of the bypass vein or residual valves. In an experimental study we could demonstrate, that the conventional methods of valve destruction are followed by an extensive trauma of the venous wall or by an incomplete rupture of the valves. After elimination of the valvular function their afibrinolytic sinus lie free in the vein lumen. We invented and tested experimentally and clinically a new valve-destroying instrument, the Elektrovalvulectome, which does not rupture the valves, but does excise them in toto. Additionally the cutting head of the instrument can be changed in situ and so adapted to the different diameters of the venous conduit. The results were excellent. We found from own hemodynamic measurements and from the literature, that the numerous theoretical advantages of the in situ venous bypass, except the better hemodynamics, are without practical relevance. From our own experiences and those of the literature we must conclude: 1. The in-situ venous bypass is a good method for femorocrural reconstructions. 2. If the distal anastomosis lies in the popliteal artery, we prefer the free orthograd venous bypass. 3. The valves should not be ruptured or incised, but excised in toto. PMID- 1876966 TI - Serum neuron-specific enolase levels after subarachnoid hemorrhage. AB - We examined serum levels of neuron-specific enolase by enzyme immunoassay in 29 patients with subarachnoid hemorrhage due to ruptured cerebral aneurysm. Serum neuron-specific enolase levels were significantly higher in patients with a poor neurological status than in patients with a good neurological status on admission, and the greater the amount of subarachnoid blood, the higher the serum neuron-specific enolase level. Patients with a good outcome had low serum neuron specific enolase levels throughout their courses. Serum neuron-specific enolase levels increased with development of delayed ischemic neurological deficits and, especially in poor outcome patients, high levels persisted until 3 weeks after the subarachnoid hemorrhage. PMID- 1876967 TI - Hypothermic protection following middle cerebral artery occlusion in the rat. AB - The effects of deep hypothermia on ischemic neuronal injury were examined using a permanent middle cerebral artery occlusion model in the rat. Animals were maintained at temporalis temperatures of either 24 degrees C or 36 degrees C and killed 6 hours after arterial occlusion. Normothermic rats displayed an average infarct volume of 25.1% +/- 1.6% of the right hemisphere, whereas hypothermic rats had an average infarct volume of 4.1% +/- 1.3% (p less than 0.001). The right/left hemispheric ratio was 1.05 +/- 0.02 in the normothermic group and 1.00 +/- 0.02 in the hypothermic group (p less than 0.05). These results suggest that hypothermia to 24 degrees C may reduce cerebral infarction and edema formation following middle cerebral artery occlusion in the rat. PMID- 1876968 TI - The use of anterior Caspar plate fixation in acute cervical spine injury. AB - Optimal management of cervical cord injury in the presence of documented instability and/or compression of neural elements remains a controversial topic. Surgery and internal stabilization of cervical spine fracture/dislocations are effective and well accepted, but controversy exists on the relative merits of the anterior versus the posterior approach as well as the optimal timing of surgical intervention. We report our experience with the Caspar technique and instrumentation for anterior stabilization in 54 patients for acute cervical spine injury. Our series consists of 38 male and 16 female patients whose ages ranged from 16 to 68 years, with a mean age of 29.2 years. Thirty-two of these patients had complete neurological sensory/motor deficits at the time of presentation, eight were neurologically intact, and 14 had preservation of some motor and sensory function. All 54 patients had radiographic evidence of posterior instability as well as anterior disruption of either a vertebral body or intervertebral disk. We found that "early" intervention (less than 24 hours after injury) was performed frequently in the neurologically compromised patients. Twelve of the 22 patients undergoing surgery less than 24 hours after admission regained significant neurological function, with 13 of 22 developing postoperative complications. In the "delayed" group (surgery more than 24 hours after injury, mean 14.3 days), 14 patients experienced postoperative complications, with 15 of 24 demonstrating neurological improvement. The eight patients who were intact did uniformly well. There was no mortality during the follow-up. All 54 patients showed a solid fusion (clinically and radiologically) within 6 months of surgery. In two cases the plates had to be removed, without risking the fusion. Our experience suggests that although anterior cervical fusion and Caspar plating remain appropriate for patients with documented anterior compromise of the canal, it should not substitute for more traditional posterior stabilization procedures. Because this route has the potential for more serious complications, it should be reserved for the cases in which anterior decompression is deemed necessary or posterior fusion was unsuccessful. With appropriate selection of patients, no adverse effect of early surgery was demonstrated. In fact, neurologically compromised patients had the benefits of increased ease of patient care and early transfer to rehabilitation. PMID- 1876969 TI - Induced hypertension during restoration of flow after temporary middle cerebral artery occlusion in the rat: effect on neuronal injury and edema. AB - The effect of hypertension instituted during restoration of flow after focal ischemia was studied. After the middle cerebral artery (MCA) of 12 rats was occluded for 2 hours, the ligatures were released and flow was restored for a period of 2 hours. In the control group, mean arterial pressure (MAP) was not manipulated. In the hypertensive group, the MAP was elevated by 25-30 mm Hg immediately after reestablishment of MCA patency. The area of neuronal injury, determined by 2,3,5-triphenyltetrazolium staining, was significantly smaller in the hypertensive group. Specific gravity, determined by microgravimetry, did not differ between groups. The data demonstrate that modest hypertension, when induced during reperfusion after 2 hours of MCA occlusion, reduces neuronal injury and does not exacerbate edema formation. PMID- 1876970 TI - Ruptured saccular aneurysm associated with duplication of the vertebral artery. AB - A case of a ruptured aneurysm arising from a duplicated segment of the intracranial portion of the vertebral artery is reported. This particular association, which can be explained by the embryological development of the vertebral artery, has not been described previously. PMID- 1876971 TI - Paraplegia in a pregnant thalassemic woman due to extramedullary hematopoiesis: successful management with transfusions. AB - The investigation and treatment of a pregnant thalassemic woman who developed severe paraplegia is presented. Magnetic resonance imaging showed a paravertebral mass infiltrating the epidural space, resulting from extramedullary hematopoiesis (marrow heterotopia). The patient was treated successfully with repeated blood transfusions and made a complete recovery. The literature (36 cases) is reviewed and the magnetic resonance imaging features of spinal extramedullary hematopoiesis are presented. The efficacy of transfusions in the management of spinal cord compression due to marrow heterotopia in thalassemic patients is discussed. PMID- 1876972 TI - Maffucci's syndrome associated with intracranial enchondroma and aneurysm: case report. AB - Maffucci's syndrome is a rare, congenital mesodermal dysplasia combined with dyschondroplasia and hemangiomatosis. Enchondromatous involvement of the skull bones is rare in this syndrome. A rare case of Maffucci's syndrome associated with enchondroma at the skull base, left internal carotid artery aneurysm, and goiter is reported. Two other previously reported cases of Maffucci's syndrome with associated aneurysms and the present case suggest that Maffucci's syndrome may be associated with aneurysm. PMID- 1876973 TI - Dural arteriovenous malformation in the anterior cranial fossa: report of a case. AB - We present an unusual case involving intracranial arteriovenous malformations in the anterior cranial fossa located symmetrically on both sides. A mixed pial and dural arteriovenous malformation, the nidus of which was localized in the brain parenchyma, was found on the right side and a pure dural arteriovenous malformation on the left side. Our case is felt to support the hypothesis of a congenital origin for dural arteriovenous malformation in the anterior cranial fossa, because the dural arteriovenous malformation coexisted with the mixed pial and dural arteriovenous malformation, which can be attributed to a disturbance of normal embryonic development. PMID- 1876974 TI - Spontaneous closure of a high-risk dural arteriovenous malformation of the transverse sinus. AB - The case of a 44-year-old woman with tinnitus of her left ear is presented. An arteriogram demonstrated a posterior dural arteriovenous malformation (AVM) on that side with drainage via dilated cortical veins into the superior sagittal sinus. No intervention was undertaken. When angiography was repeated 7 years later, no dural AVM was seen. PMID- 1876975 TI - Alfred Reginald Allen: the mythic career of a gifted neuroscientist. PMID- 1876976 TI - Familial medulloblastoma in siblings: report in one family and review of the literature. PMID- 1876977 TI - Occupational cervico-brachial disorders among dentists. Analysis of ergonomics and locomotor functions. AB - The aim of the investigation was to compare dentists with and without occupational cervicobrachial disorders with regard to the mobility of the neck and shoulders and the static endurance of the shoulder muscles. Further, differences in working position and the task performance on a stimulated case were to be analysed. The investigation was carried out during a visit to the workplace of 143 dental officers in the Public Dental Service in Malmohus District and the Municipality of Malmo. Of these dentists, 96 had signs of cervico-brachial disorders and discomfort while 47 had not. The ergonomic examination showed, that significantly more dentists without symptoms of pain applied a wedge cushion under the upper part of the back of the patient to get an optimum view (p less than 0.05). It was also found that significantly more dentists without symptoms were aware of and utilised the naturally arising pauses in their work than dentists with pain and discomfort. Further dentists with cervico-brachial disorders kept their head sidebent and rotated to a greater extent than dentists without symptoms (p less than 0.01). No significant difference was found between the two groups concerning mobility of the neck and shoulders. Significant differences were found between women with and without cervico-brachial systems. PMID- 1876978 TI - Tobacco habits among teenagers in the city of Goteborg, Sweden, and possible association with dental caries. AB - Frome nine dental clinics within the Public Dental Service in the City of Goteborg, 2145 patients aged 14 to 19 answered a questionnaire concerning their tobacco habits. Tobacco was used in some form by 27 per cent of the patients and use increased with age. Smoking was more common among girls than among boys: 24 and 12 per cent, respectively. The statistical analyses showed that smoking as a habit and an increased number of cigarettes smoked per day are positively correlated with increases in the number of decayed, missing and filled teeth and the number of initially decayed proximal surfaces. Further, all caries epidemiological data were significantly higher among patients with tobacco habits compared to non-users. It can be concluded that there is a correlation between the tobacco habit and increased caries prevalence. However, dietary and oral habits have to be further elucidated before any definite conclusions can be made regarding the effect of the tobacco habit per se on the development of caries. PMID- 1876979 TI - Is snuff a potential risk factor in occlusal wear? AB - Oral snuff contains fairly high percentages of inorganic, potentially abrasive elements and the use of snuff has been identified as one factor that contributes to occlusal wear. In the first part of the present study, the snuff habits of 100 users were investigated. 41 per cent reported that they sometimes got snuff between their teeth and another 14 per cent said that this happened often. Thirteen and six per cent, respectively, admitted that they sometimes of often used snuff as chewing tobacco. In the second part, an experimental model, using a so-called Bruxcore, was set up to estimate the degree of occlusal wear when chewing snuff compared to when chewing with nothing in the mouth. After 3000 chewing strokes on each plate, the wear of the plate used while chewing snuff was significantly less compared to the plate used while chewing with nothing in the mouth. The most likely explanation for this finding is that the salivary flow was more than twice as high when chewing snuff compared to chewing with nothing in the mouth, and that the saliva serves as a lubricant that protects the surface from wear. It is concluded that the use of oral snuff is not an important risk factor in occlusal wear. PMID- 1876980 TI - Secondary caries related to various marginal gaps around amalgam restorations in vitro. AB - Secondary caries lesions were produced in vitro by immersing human tooth-blocks with amalgam restorations every third day for 4 weeks in glucose- or sucrose containing broth inoculated with a strain of Streptococcus mutans. The lesions at the cavity walls were related to various standardized micro-spaces (0, 30, 40, 60 and 80 microns) around the restorations. When a thick, sucrose induced layer of plaque covered the margin, dentine caries was found in all cases where a gap was present (30 microns or more). In the presence of a thin, glucose induced layer of plaque, dentine caries was detected only in the specimens with 60 and 80 microns gap-widths. Caries lesions were detected on the outer free enamel surfaces in all specimens. Lesions in the enamel of the cavity walls were observed with polarized light in 46% in the presence of sucrose- and in 21% in the presence of glucose induced plaque. PMID- 1876981 TI - Regression of phenytoin-induced gingival overgrowth after withdrawal of medication. AB - The regression of phenytoin-induced gingival overgrowth after withdrawal of medication was studied in 10 children. After only one month a statistically significant (p less than 0.05) in buccolingual dimension of the marginal gingiva was observed in both the maxillary and mandibular incisor areas. Children diagnosed as responders (i.e. exhibiting pseudopockets) showed a more rapid and significantly greater decrease (p less than 0.05) in buccolingual dimension at 1 and 3 months after withdrawal of PHT medication than non-responders. Compared to a control group of children on other antiepileptic drugs, no significant differences could be found in the thickness of the marginal gingiva six months after withdrawal of medication. PMID- 1876982 TI - Salivary mutans streptococci and caries prevalence in 8-year-old Swedish schoolchildren. AB - The aim of this study was to obtain cross-sectional information about the quantitative distribution of salivary mutants streptococci assessed with a clinically applicable microbiological method and the relation to dental caries in young schoolchildren. A total of 355 8-year-old children were examined for the presence and number of mutants streptococci in saliva by a specially prepared strip, the "Strip-mutans" method, cultivated in a selective broth. The strips were first visually examined and grouped by aid of a templet provided by the manufacturer and thereafter transferred to a laboratory for enumeration of colony forming units (CFU) with aid of a stereomicroscope. Caries scores were obtained from the dental records. Mutans streptococci were identified in 70% of all children. 46% were free from the bacterium or harboured low levels (0-10 CFU) while high levels (greater than or equal to 500 CFU) were found only in 6% of the material. Strong positive correlations (p less than 0.001) were found between different levels of mutans streptococci infection and the caries experience in both the primary (dmfs) and the permanent (DMFS) dentition. A statistically significant correlation between the direct examination and the microscopic enumeration was disclosed (r = 0.84). The bacterial culturing technique used in this study proved to be practical and reliable and thus useful in clinical routines of pediatric dentistry. PMID- 1876983 TI - [Clinical nursing--Bobath' principles]. PMID- 1876984 TI - [Working environment--a harsh working place]. PMID- 1876985 TI - [Health, sickness, suffering, death. 2. Wholeness--human dignity and medical science]. PMID- 1876986 TI - [What do laws and agreements say about vacation conditions?]. PMID- 1876987 TI - [It happens every day]. PMID- 1876988 TI - [Clinical nursing--no easy shortcuts]. PMID- 1876989 TI - [An elegy]. PMID- 1876990 TI - [Drug information--old wine in new flasks. Assortment of insulin modernized]. PMID- 1876991 TI - [Nursing research--appreciation. Interview by Grethe Kjaergaard]. PMID- 1876992 TI - [Health, sickness, suffering, death. 3. Wholeness--culture and dying]. PMID- 1876993 TI - [The weakest don't have to pay]. PMID- 1876994 TI - [Psychiatric nursing--brute force. Interview by Teddy Osterlin Koch]. PMID- 1876995 TI - [Psychiatric nursing. Violent patients need security]. PMID- 1876996 TI - [AIDS staff takes flight]. PMID- 1876997 TI - [Hospital & Rehab 91. Thus far the biggest health fair]. PMID- 1876998 TI - [Health, sickness, suffering, death. 4. Wholeness--dying and the individual]. PMID- 1876999 TI - [Apoplexy and automobile driving]. PMID- 1877000 TI - [What do we know about it?]. PMID- 1877001 TI - [Hidden camera. Interview by Mogens Cuber]. PMID- 1877002 TI - [Soviet Union--snowball effect]. PMID- 1877003 TI - [On the heels of infection]. PMID- 1877004 TI - [Nursing research. Affectionate research. Interview by Grethe Kjaergaard]. PMID- 1877005 TI - [Why does one want to have the experience?]. PMID- 1877006 TI - [Philosophy. Rejection of purely situational ethics]. PMID- 1877008 TI - [EEC. Minimal requirements for computer terminal work stations]. PMID- 1877007 TI - [Social medicine. Better health with a good social network]. PMID- 1877009 TI - [Mental health. Nursing care in district psychiatry]. PMID- 1877010 TI - [Mental health. More mentally ill with substance abuse in welfare home. Interview by Lars Peter Bergqvist]. PMID- 1877011 TI - [Mental health. Monday on day watch]. PMID- 1877012 TI - [Mental health. Care and restraint]. PMID- 1877013 TI - [Mental health. Now it is here ... continuing education]. PMID- 1877014 TI - [Mental health. A valid discharge]. PMID- 1877015 TI - [Mental health. Art and knowledge in psychiatric nursing]. PMID- 1877016 TI - [It concerns mental health]. PMID- 1877018 TI - [Mental health. When the healing is by strides]. PMID- 1877017 TI - [Mental health. Brian on a short leash]. PMID- 1877019 TI - [Mental health. Departure in psychiatry]. PMID- 1877020 TI - Teamwork helps rural hospital rise to the occasion. PMID- 1877021 TI - HIV bill passes House committee, subcommittee considers mandatory testing. PMID- 1877022 TI - TDH says watch for Listeria infection. PMID- 1877023 TI - Health commissioner Robert Bernstein talks about public health in Texas. PMID- 1877024 TI - The shape of things to come: PPRC ponders payment reform. PMID- 1877025 TI - The lowdown on low fees in Texas Medicaid. PMID- 1877026 TI - R-e-s-p-e-c-t. The public image of physicians. PMID- 1877027 TI - 'Bill of Rights' for physicians who serve--don't leave for the next war without it. PMID- 1877028 TI - Texas physician did the right thing in publicized prescription forgery. PMID- 1877029 TI - Look before you sign on the dotted line with HMOs and PPOs. PMID- 1877030 TI - Sexual abuse of children. AB - Sexual abuse of children is a pervasive and growing problem, which has demanded the attention of several professional groups. Because most children never reveal the abuse, understanding the psychodynamics involved is fundamental to the detection of these victims. Physicians should be aware of the masked clinical and behavioral indicators of sexually abused children that signal the need for further questioning. Through appropriate inspection of genitalia and anus in routine examination of the child, the physician can establish rapport and a foundation of trust critical for disclosure of abuse. The history the child gives is the most important evidence and is most credible when spontaneous, consistent, and detailed. Physicians must report any suspicion of child abuse to the Texas Department of Human Services (TDHS) and/or law enforcement agencies. Finally, physicians can help prevent such sexual abuse by providing anticipatory guidance for parents and caretakers of children. PMID- 1877031 TI - How trimester of entry into prenatal food program affects birth weight. AB - During 1988, 80% of women in the Special Supplemental Food Program for Women, Infants, and Children (WIC) in Texas enrolled in the program after the first trimester of pregnancy. Infants born to these women displayed higher rates of low birth weight than those born to women who entered WIC during their first trimester. Infants born to women who enrolled in WIC during the second trimester had higher birth weights than those born to women who waited until the third trimester to enter WIC. If the trimester of WIC enrollment for Texas is adjusted with use of an unweighted national sample, more women would have enrolled during the first two trimesters of pregnancy and 362 fewer babies with low birth weight would have been delivered by WIC enrollees during 1988. Efforts should be made to encourage early enrollment in WIC--and prenatal care--for women at high risk for delivering low birth weight infants. PMID- 1877032 TI - Comprehensive care for patients with hemophilia: an expanded role in reducing risk for human immunodeficiency virus. AB - Hemophilia is an inherited coagulation disease that affects approximately 1 in 5,000 to 10,000 males worldwide. Chronic joint disease and other long-term complications of recurrent bleeding persist in patients with hemophilia despite improved and more available clotting protein concentrates. The best care can be provided to patients who are followed regularly in specialized treatment centers. Services of every "comprehensive" hemophilia treatment center (HTC) have expanded since previous treatment with clotting factor concentrates infected many hemophilics with the human immunodeficiency virus (HIV). Each HTC offers therapeutic, educational, and counseling expertise in care for the complications of HIV. A nationwide network of specialists now provides care for patients with hemophilia and related congenital abnormalities. In Region VI (Texas, Oklahoma, and Arkansas), the treatment centers and their affiliates provide medical, psychosocial, orthopedic/physical therapy, dental, and case management services. Extramural funded research programs provide care and laboratory testing at no cost to individual subjects. PMID- 1877033 TI - Updated definition of brain death in Texas. AB - In most instances, brain death is established on the basis of straightforward clinical findings in adult patients having suffered head trauma or cerebral hemorrhage. In exceptional instances, including infants or adults having the neurologic criteria with a backdrop other than trauma or hemorrhage, or who are being treated with barbiturate coma, a different diagnostic procedure is necessary. Various considerations in brain death diagnosis in these exceptional circumstances are listed, with an update of ancillary diagnostic procedures. Reasons for avoiding unnecessary delays of diagnosis are underscored. PMID- 1877034 TI - Lung function in adult idiopathic scoliosis: a 20 year follow up. AB - Severe idiopathic scoliosis may lead to respiratory failure, which can be treated by assisted ventilation. Twenty four patients with surgically untreated idiopathic scoliosis who had been examined in 1968 were re-examined in 1988 to assess changes in lung function and risk factors for respiratory failure. The patients were aged 15-67 years in 1968 and had a scoliotic angle of 10-190 degrees and a vital capacity of 1.0-6.0 litres. Spirometric values and scoliotic angles were determined in 1968 and 1988, and arterial blood gas tensions in 1988. The decline in spirometric values over the 20 years was of the same magnitude as the predicted decline due to aging. Arterial blood gas tensions in 1988 were strongly correlated with the scoliotic angles and spirometric indices recorded in 1968. Hypoxaemia and hypercapnia was seen in four patients in 1988 (then aged 43 67 years) and these were the four patients who had a vital capacity below 43% predicted in 1968. The remaining 20 patients had blood gas values within normal limits. Two further patients had died from respiratory failure before 1988, so a total of six patients had developed respiratory failure. In a multiple logistic analysis vital capacity expressed as % predicted in 1968 was the strongest predictor of the development of respiratory failure, followed by the scoliotic angle. Respiratory failure occurred only in patients who had a vital capacity below 45% predicted in 1968 and an angle greater than 110 degrees. Thus respiratory failure develops in adults with scoliosis with a large angle and a low vital capacity when normal aging reduces the ventilatory capacity further. Such individuals merit close follow up. PMID- 1877035 TI - Chronic persistent cough and gastro-oesophageal reflux. AB - Chronic cough persisting for two months or more that remains unexplained after extensive investigations is a common clinical problem. The purpose of this study was to determine whether such cough is associated with otherwise asymptomatic gastro-oesophageal reflux. Thirteen patients with chronic persistent cough that was unexplained after a standard diagnostic assessment were identified. All were non-smokers. The mean (SE) duration of cough was 17.8 (8.0) months. Ten had never had reflux symptoms and three had had mild symptoms only after the onset of the cough. All the patients completed standardised cough diary cards for eight weeks and underwent 24 hour ambulatory oesophageal pH monitoring. A reflux episode was defined as a fall in oesophageal pH to below 4.0. Nine control subjects were matched for age, lung function, and body mass index. The patients experienced significantly more episodes of reflux per 24 hours than the controls (115.8 (SE 31.7) versus 4.7 (1.4) and longer reflux episodes (15.5 (5.8) versus 1.7 (0.5) minutes), and the oesophageal pH was below 4.0 considerably longer (84.5 (20.2) versus 3.8 (1.3) minutes). Cough occurred simultaneously with 13% (2.2%) of reflux episodes and within five minutes in another 35% (5.8%) of episodes, whereas gastro-oesophageal reflux occurred simultaneously with 78% (5.5%) of cough episodes and within five minutes in another 12% (2.3%) of episodes. It is concluded that chronic persistent cough that remains unexplained after a standard diagnostic assessment is associated with otherwise asymptomatic gastro oesophageal reflux. It is suggested that a self perpetuating mechanism may exist whereby acid reflux causes cough via a local neuronal oesophageal-tracheo bronchial reflex, and the cough in turn amplifies reflux via increased transdiaphragmatic pressure or by inducing transient lower oesophageal sphincter relaxation. Further study of this mechanism and the role of specific antireflux treatment in chronic persistent cough is warranted. PMID- 1877036 TI - Exercise but not methacholine differentiates asthma from chronic lung disease in children. AB - Bronchial provocation challenges with exercise and methacholine were performed on the same day or within a short interval in 52 children with asthma, 22 with other types of chronic lung disease (including cystic fibrosis), and 19 control subjects with no evidence of chronic lung disease. There were no significant differences in the baseline lung function before the two types of challenge in the individual groups and differences between the patients with asthma and with chronic lung disease were minor. When the mean -2 SD of the methacholine response of the control group was taken as the lower limit of normal, 49/52 (94%) patients with asthma and 18/22 (82%) with chronic lung disease responded abnormally. In contrast, with the mean +2 SD of the exercise response of the control group as the upper limit of normal, 41/52 (79%) asthmatic patients responded but none of those with chronic lung disease. Thus the response to the two types of challenge helps to distinguish asthma from other types of chronic lung disease in children. PMID- 1877037 TI - Budesonide and terbutaline or terbutaline alone in children with mild asthma: effects on bronchial hyperresponsiveness and diurnal variation in peak flow. AB - The effects of treatment with budesonide (200 micrograms twice daily) and terbutaline (500 micrograms four times daily) has been compared with the effects of placebo and terbutaline in 27 children with mild asthma, aged 7-14 years, in a double blind, randomised placebo controlled study over eight weeks. Bronchial responsiveness (PC20 histamine), lung function, the amplitude of diurnal variation in peak expiratory flow (PEF), and symptom scores were measured. Baseline FEV1 was over 70% predicted and PC20 histamine less than 8 mg/ml. Twelve children were treated with budesonide and terbutaline and 15 with placebo and terbutaline. After four and eight weeks of treatment the change in PC20 was significantly greater after budesonide and terbutaline than after terbutaline alone by 2.1 (95% CI 0.5-3.8) and 1.3 (95% CI 0.1-2.5) doubling doses respectively. Mean FEV1 did not change in either group. The change in afternoon and nocturnal PEF was significantly greater after budesonide and terbutaline than after terbutaline alone. The amplitude of diurnal variation in PEF did not change significantly in either group. Peak flow reversibility decreased in the budesonide group. There were no differences between treatments for cough and dyspnoea, but wheeze improved in the budesonide group. The children with mild asthma treated with budesonide and terbutaline showed improvement in bronchial responsiveness, afternoon and nocturnal PEF, and symptoms of wheeze and a fall in peak flow reversibility by comparison with those who received terbutaline alone. PMID- 1877038 TI - Increased platelet aggregate formation in patients with chronic airflow obstruction and hypoxaemia. AB - Platelet aggregate formation in vivo was assessed by means of the platelet aggregate ratio and from platelet release products (beta thromboglobulin, platelet factor 4, thromboxane B2) in 23 patients with chronic airflow obstruction with and without hypoxaemia and in 10 control subjects without respiratory disease. Eight of the 11 hypoxaemic patients were having long term oxygen therapy. The platelet aggregate ratio was lower in the hypoxaemic patients (0.88 (SE 0.03] than in the non-hypoxaemic (0.97 (0.01] and control groups (1.00 (0.02], and there was a trend to lower aggregate ratios in the more hypoxaemic patients. Platelet release products in the peripheral venous blood were not increased in the patients or control subjects. Platelet behaviour is altered in chronic hypoxaemia and this enhanced platelet activity could contribute to the pulmonary vascular damage found in these patients through direct effects or mediator release. PMID- 1877039 TI - Phosphodiesterase inhibitors: new opportunities for the treatment of asthma. PMID- 1877041 TI - Surgical treatment of carcinoma of the oesophagus. PMID- 1877040 TI - Intramural oesophageal dissection. PMID- 1877042 TI - Statistics in respiratory medicine. 3. Scale, parametric methods, and transformations. PMID- 1877043 TI - Pulmonary haemosiderosis associated with left atrial myxoma. AB - A patient with features suggesting pulmonary haemosiderosis was found to have a myxoma. The pulmonary lesion cleared after excision of the tumour. PMID- 1877044 TI - Successful pulmonary resection after spontaneous hemopneumothorax in the Eisenmenger syndrome. PMID- 1877045 TI - Squamous cell carcinoma occurring in the wall of a chronic aspergilloma. AB - An aspergilloma that occurred within an area of bronchiectasis in a 52 year old man persisted for 12 years despite medical and surgical treatment. A squamous cell carcinoma developed in the wall of the cavity. PMID- 1877046 TI - Measures of reversibility in response to bronchodilators in chronic airflow obstruction. PMID- 1877047 TI - Risk of tuberculosis in immigrant Asians: culturally acquired immunodeficiency. PMID- 1877048 TI - An unusual esophageal foreign body perforation--a case report and review of the literature. AB - Esophageal foreign body remains a common clinical problem. Esophageal perforation is an uncommon associated condition which almost affects invariably the esophagus. A rare case of cervical esophageal perforation secondary to an unexpected migration of a swallowed foreign body is presented. Methods of treatment are discussed and the literature is reviewed. PMID- 1877049 TI - Congenital pulmonary arteriovenous fistula: a rare cause of cyanosis in childhood. AB - Two children (both females) aged 15 months and 4 years are described as very rare cases of central cyanosis in childhood being caused by a congenital pulmonary arteriovenous fistula. The initial diagnosis was made based on cyanosis and chest radiographs, with normal physical, ECG, and radiological findings of the heart. They had no family history of the Rendu-Weber-Osler syndrome. The patients underwent cardiac catheterization and pulmonary angiography, where the diagnosis was confirmed. After the surgery, both were symptom-free, and had no evidence of the disease. PMID- 1877050 TI - A case of an intramural coronary artery associated with transposition of the great arteries. AB - One case of an intramural coronary artery in association with transposition of the great arteries is presented. A 16-month-old infant was admitted for the second-stage operation of complete transposition after a subclavian patch plasty for the aortic isthmus stenosis, division of the persisting arterial duct, and pulmonary artery banding had been performed in the first-stage operation soon after birth. The primarily planned arterial switch operation was, however, not performed because of an unusual coronary artery morphology and pattern--a separated origin of both coronary arteries from the posterior, "facing" sinus of Valsalva and an intramural course of the left anterior descending artery. This very rare case of coronary artery variation is presented from the surgical point of view. PMID- 1877051 TI - Congenital giant arteriovenous malformation in a 31-year-old male. AB - In this case presentation we report the history of a 31-year-old male suffering from a congenital giant arteriovenous malformation (AVM) of the neck and the right chest wall over the course of 12 years. This vascular tumor was fed by dilated arteries, branches of the right external carotid, and both subclavian arteries. The first therapeutic procedure was an isolated ligation of the draining arteries, which was not successful as angiography showed two years later. As the patient rejected any further therapy, the enormous growing tumor was again treated 9 years later. At this time an interdisciplinary management involving radiologists and surgeons was arranged. Superselective embolization preceding surgical radical tumor resection was performed. After a follow-up period of almost 1 year no further signs of progression were seen, except the postsurgical embolization of one collateral external carotid branch and a beginning skin necrosis which was to be expected. However, recently progression has become evident, but the patient has refused further treatment. PMID- 1877052 TI - Reflections on heart transplantation. PMID- 1877053 TI - Endothelial function and contractility of human vena saphena magna prepared for aortocoronary bypass grafting. AB - The aim of this study was to examine whether contractility and endothelial function of the human saphenous vein prepared for aortocoronary bypass grafting are altered by the surgical technique, e.g. cannulation and gentle distension of the vessel. Two segments (2 cm length each) of native vena saphena magna and 2 segments (2 cm length each) of the same vessel prepared for coronary bypass grafting were taken for further experimentation. After ligation of all side branches the segments were cannulated and arranged in two systems (with two segments each) in a serial manner (system I: prepared vessel followed by a native segment; system II: native vessel followed by a prepared segment) and perfused with Tyrode's solution at a constant flow rate of 20 ml/min (PO2 = 45 mmHg). Pressure gradient was measured continuously over each segment as a function of the vessel's radius according to the Hagen-Poiseuille equation. Endothelial and smooth muscle function was checked by perfusion with increasing concentrations of acetylcholine (ACH) to provoke the release of endothelium-derived relaxing factor (EDRF) (ACH; 0.3, 1, 3, 10, 30 mumol/L) after precontraction of the vessels with 1 mumol/L norepinephrine (NE). This showed normal contractility and ACH-induced relaxation in the native vessels but a reduced contractile response and a total lack of ACH-EDRF-induced relaxation in the prepared vessels. Perfusion with 5 hydroxytrytamine (5-HT) (0.25, 0.5, 1, 10 mumol/L for 10 min each concentration) resulted in marked constriction of all vessels with preserved contractility which could be completely prevented by pretreatment with the 5-HT2-receptor antagonist ketanserine (20 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877054 TI - An alternative technique for orthotopic cardiac transplantation, with preservation of the normal anatomy of the right atrium. AB - The standard technique for orthotopic cardiac transplantation implies large atrial anastomoses which do not preserve the anatomical integrity of the donor atria. This may become a potential source of electrophysiological and mechanical atrial dysfunction, especially in the right atrium with the sinus node and the sensitive low-pressure atrioventricular valve. As an improvement we suggest an alternative technique which we have recently developed for orthotopic cardiac transplantation; it combines the simple, convenient left atrial connection of the standard technique with individual anastomoses of the superior and inferior venae cavae, preserving the right atrium of the donated heart intact. This technique and our first results in two cases are described. Postoperatively, no arrhythmias and no signs of tricuspid insufficiency were observed. PMID- 1877055 TI - PTFE sutures for mitral valve reconstruction--histological findings in man. AB - A case of mitral valve reconstruction with replacement of the chordae tendineae by polytetrafluoroethylene (PTFE) sutures is described in a 52-year-old man. 21 days after operation mitral valve insufficiency due to rupture of a natural chorda led to reoperation with mitral valve replacement. The cardiac valve tissue was examined both macroscopically and microscopically. It showed a proliferation of fibroblasts. However, there was no endothelial cell layer detectable. To the best of our knowledge our case is the first report of the histological changes in human cardiac valvular tissue after implantation of PTFE sutures. PMID- 1877056 TI - Early neurological and electroencephalographic changes after coronary artery surgery in low-risk patients younger than 70 years. AB - Between September 1986 and January 1988 neurological examination and electroencephalography (EEG) was performed before and one week after coronary artery bypass grafting in 66 patients younger than 70 years. Twenty patients were randomized to a bubble oxygenator without an arterial line filter (Group I), 22 patients to a bubble oxygenator with a depth adsorption filter (Group II), and 24 patients to a membrane oxygenator without a filter (Group III). No patient suffered a major stroke but early central nervous system dysfunction occurred after the operation in four patients (20%) in Group I, in four patients (18%) in group II and in two patients (8%) in group III. The difference between group I and III was not statistically significant but a larger number of patients in the groups might alter this. Our prospective study demonstrated a significant incidence of neurologic dysfunction in a low risk patient population undergoing standard coronary artery bypass surgery. PMID- 1877057 TI - Postoperative arrhythmias and risk factors after open heart surgery. AB - Cardiac arrhythmias were recorded during 24 hours in 40 consecutive patients requiring open-heart surgery, using continuous Holter monitoring. Most patients developed both supraventricular and ventricular arrhythmias. Complex ventricular arrhythmias were detected in 31 patients (78%) and 2 patients suffered an immediate postoperative myocardial infarction. The following risk factors were considered: age, sex, type of heart disease, preoperative left ventricular ejection fraction, cardiopulmonary bypass and aortic clamping duration, length of anesthesia, dopamine administration, and maximal level of CK and CK-MB. Only dopamine administration, even in low renal dose, was associated with the number and severity of ventricular arrhythmias. PMID- 1877058 TI - Preoperative assessment of the likelihood of infection of the lower respiratory tract after cardiac surgery. AB - Lower-respiratory-tract infections are among the most frequent complications observed in the intensive care unit, leading to delayed postoperative recovery time and increased costs and mortality. We have tried to evaluate the prognostic value of perioperative bacteriology of tracheal aspirates in assessing the risk of such complications. In a prospective study aspirates of 100 patients undergoing cardiac surgery were taken immediately after intubation and were analysed for microorganisms by Gram-stain and microbiological cultures using standard procedures. All patients received perioperative antibiotic prophylaxis with a single dose of 2 g ceftriaxone intravenously. From 26 patients with bacteriologically positive tracheal secretion, 8 (30.7%) developed lower respiratory tract infection whereas only 1 of 72 patients (1.4%) with negative bacteriological results developed this complication. Smoking (p less than 0.01) and abnormal preoperative lung function (p less than 0.01) were significantly more frequent in patients developing postoperative pneumonia. Regarding the results of this study, the risk of developing pulmonary infection in the early postoperative course after cardiac surgery can be estimated from the tracheal aspirates. PMID- 1877059 TI - Bronchoscopic removal of foreign bodies in children: retrospective analysis of 822 cases. AB - At the Department of Thoracic and Cardiovascular Surgery of Hacettepe University, a total number of 822 pediatric bronchoscopies were performed from 1984 through 1990 for suspected foreign body aspiration. Of the children 65.3% were boys and 34.7% were girls ranging in age from one month to 14 years. Definitive statement of foreign-body aspiration was obtained from 394 patients. Unilateral hyperaeration, atelectasis, and unilateral parenchymal infiltration were the most common radiological findings. In all endoscopic procedures, a pediatric rigid bronchoscope was used under general anesthesia and controlled ventilation. Foreign bodies were found in 77.7% of the 822 patients. In the rest of the children inflammatory disorders were confirmed. The foreign bodies most commonly found in 639 patients were sun-flower seeds (21.1%), beans (10.4%), water-melon seeds (10%), and hazelnuts (9.8%). In our presented series, the incidence of non fatal complication was 1.8%, apart from these patients 5 of them (0.6%) died after the bronchoscopic procedures. PMID- 1877060 TI - Tracheal agenesis: an unresolved problem. AB - A case of tracheal agenesis diagnosed at birth is discussed in which surgical correction was attempted. Both main bronchi were divided and anastomosis of the main right bronchus to the larynx was attempted, after intrapericardial release of the right lung and severing of the lower pulmonary ligament: bronchoplastic reconstruction of the trachea was impossible. We think that tracheal agenesis, a rare cause of respiratory distress in the newborn, has no suitable therapy today. It is justified to attempt surgical correction if any promising device is at hand or if any doubt exists that an uncorrectable situation is present. PMID- 1877061 TI - Parameters of the circadian rhythm of pineal melatonin secretion affecting reproductive responses in Siberian hamsters. AB - The major function of the mammalian pineal gland appears to be its central role in photoperiodism. The pineal hormone, melatonin, is synthesized and secreted primarily at night, under the control of a circadian oscillator that is entrained to the light-dark cycle. Both the circadian phase and the duration of the nocturnal peak of melatonin secretion are established primarily by interactions between the endogenous circadian oscillator and the daily photic cycle. The duration of the melatonin peak varies inversely with day length, and this relationship between day length and the duration of each circadian melatonin peak appears to be an integral part of the photoperiodic mechanism. When pinealectomized animals are given daily melatonin infusions of long duration, they exhibit physiologic responses that normally are observed during exposure to short day photoperiods; when administered short-duration melatonin infusions, the animals display long photoperiod-type responses. In addition to the importance of the duration of each melatonin peak, certain other parameters appear to be significant. If a long-duration infusion of melatonin is interrupted by a period of 2 hours or more without melatonin (i.e., to produce two short duration infusions), the responses are those typical for long day-exposed animals. Thus, to elicit short day-type responses, each long-duration melatonin peak must be relatively continuous; responses are not determined simply by the total time of exposure to melatonin in each circadian cycle. Also, long-duration melatonin peaks may not be effective to elicit photoperiod-type responses unless they are present at frequencies of nearly once every 24 hours or more. PMID- 1877062 TI - The influence of portacaval anastomosis on gonadal and anterior pituitary hormones in a rat model standardized for gender, food intake, and time after surgery. AB - Portacaval anastomosis causes delayed growth, decreased testes and liver weights, and elevated estradiol serum levels in male rats compared with sham-operated controls. Female rats treated with portacaval anastomosis grow at a normal rate despite changes in liver weight and estradiol levels similar to those observed in the male rats. This study examined the pituitary gonadal axis in both genders in this animal model. The rats receiving portacaval anastomosis were compared with both pair-fed and sham-operated control groups. Portacaval anastomosis decreased serum testosterone and increased estradiol in the male animals, while both testosterone and estradiol were increased in the females compared with gender matched pair-fed and sham controls. Because pair feeding lowers male testosterone to a lesser extent, impaired nutrition may partially account for the decrease in the males treated with portacaval anastomosis. The ratio of estradiol to testosterone increased following anastomosis in male rats, but it was decreased in similarly treated females. Portacaval and anastomosis decreased luteinizing hormone without changing follicle-stimulating hormone in both male and female rats compared with sham-operated controls. Growth hormone was significantly decreased in male portacaval-treated rats compared with sham- and pair-fed animals. Increased insulin levels were found in both male and female pair-fed and portacaval anastomosis-treated animals. These data suggest that following portacaval anastomosis in rats, growth, serum testosterone, estradiol to testosterone ratios, and growth hormone are altered in a gender-specific manner with gender-independent changes in insulin and luteinizing hormone levels. These gender-specific effects may protect the portacaval anastomosis-treated female rat from growth retardation. PMID- 1877063 TI - Production and biologic action of relaxin within the ovarian follicle: an overview. AB - The studies described here support the concept that relaxin is a product of the ovarian follicle and interacts with systemic hormones in the local regulation of the ovary. This report reviews the work indicating that relaxin is a product of the ovarian follicle and presents evidence for the biologic action of relaxin within the follicle. Production of relaxin by cells of the theca interna was given support by immunocytochemical localization work, in vitro production studies, and detection of relaxin mRNA by in situ hybridization. The relaxin content of porcine follicular fluid was shown to increase with development induced by gonadotropins. During thecal cell culture, luteinizing hormone and porcine follicular fluid increased relaxin secretion, whereas the presence of granulosa cells was without effect. A biologic action for relaxin on connective tissue remodeling was supported by an increase in follicle-stimulating hormone stimulated plasminogen activator activity by granulosa cells. Additional work is needed to investigate the possibility of other roles for relaxin within the follicle, to identify relaxin receptors, and to explore the interaction of relaxin with endocrine and other paracrine factors in the ovary. PMID- 1877064 TI - The role of the adenylyl cyclase system in the regulation of corpus luteum function in the human and in nonhuman primates. AB - We have reviewed the properties of luteinizing hormone/human chorionic gonadotropic (LH/hCG)-sensitive adenylyl cyclase (AC) of human corpus luteum (CL) and its regulation by several hormones and nonhormonal activators. We have also described the changes in enzyme activity in membrane preparations of human and cynomolgus monkey CL obtained at various stages of the menstrual cycle and pregnancy. The data have been analyzed with respect to the functional status of the luteal tissue and to the species differences among primate CL. In the menstrual cycle, luteal AC responsiveness to LH/hCG was detectable during the midluteal phase, but not during the late luteal phase or in the follicular phase of the following cycle. In addition, nonhormonal stimulation was high in CL obtained during the midluteal and late luteal phases, but declined drastically by the follicular phase of the next cycle. In early pregnancy, the enzyme was unresponsive to LH/hCG stimulation, yet its sensitivity to nonhormonal stimulation was similar, if not identical, to that of midluteal phase CL. Functional activity was also evident at the end of pregnancy. These results demonstrate that expression of AC activity in primate luteal membrane changes significantly with varying hormonal status under physiologic conditions. It is concluded that the AC system in luteal membranes is an effective model to study the mechanisms that regulate function and life span of the human and nonhuman primate CL. PMID- 1877065 TI - In vitro effects of dihydrotestosterone on granulosa cell production of estrogen and progesterone. AB - To investigate the direct effects of androgens on follicle development, intact, immature female rats were given 8 IU PMSG (0 hour) and four injections of either vehicle or dihydrotestosterone (DHT), 1 mg/kg body weight, at 0, 12, 24, and 36 hours after PMSG. Granulosa cells from small (less than 200 microns), medium (200 to 400 microns), and large (greater than 400 microns) follicles were isolated and cultured in the presence or absence of 0.5 microM DHT in vitro for 48 hours, and the medium was assayed for progesterone and estrogen. Results show that DHT caused an increase in progesterone accumulation in all granulosa cells, regardless of follicle size. However, DHT inhibited estrogen accumulation in granulosa cells from different-size follicles and the inhibition varied depending on the duration of androgen exposure in vivo. The inhibition of estrogen accumulation was seen in granulosa cells from small follicles without prior exposure to DHT in vivo, while an inhibition of estrogen accumulation was seen in granulosa cells from medium and large follicles exposed to DHT treatment in vivo. Taken together, the results of experiments with in vivo and/or in vitro DHT treatment show that the androgen increases granulosa cell progesterone synthesis regardless of follicle size. However, the estrogen accumulation by granulosa cell is dependent on follicle size and duration of DHT exposure. PMID- 1877066 TI - Estrogen receptor stereochemistry: ligand binding and hormonal responsiveness. AB - Estrogen stimulation of the uterus produces a spectrum of biochemical responses that are customarily linked together. This report is an overview of a series of studies by our laboratory investigating the role of different ligand structures in eliciting hormonal responses. Diethylstilbestrol (DES) and certain structural analogs, indenestrol A (IA), indenestrol B (IB), and pseudo-DES, were used as probes to segregate various genomic responses previously considered interrelated, most notably the events of specific protein synthesis and DNA synthesis. These compounds have weak uterotrophic activity; however, they interact with high affinity specifically with mouse uterine estrogen receptors (ERs). All of them produce stoichiometrically similar amounts of ER complex in the nucleus. Indenestrol A and IB possess a single chiral carbon atom and exist as a mixture of enantiomers (ENTs). Competitive binding assays of pure ENTs and cytosolic ERs demonstrated a stereochemical chiral preference for the IA isomer but not IB. This preference was also evident from nuclear ER occupancy experiments. Biologic activity of the IA ENTs also demonstrated differences as seen by receptor binding. Ornithine decarboxylase (ODC) activity was stimulated 600% by DES and partially by IA (rac). All of the ODC activity produced by IA (rac) was due to the IA(C3)-S ENT. Uterine DNA synthesis was measured after treatment with the IA compounds. Indenestrol A (rac) increased DNA synthesis to 40% of the level seen with DES. The weak ENTs showed no activity and the active ENTs were weaker than the IA racemic. These compounds should be useful probes for studying the individual responses involved in estrogen-induced uterine growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877067 TI - [Stimulation or stagnation of research on aging?]. PMID- 1877068 TI - [The Dutch Reading Test for Adults: a measure of premorbid intelligence level]. AB - The construction of the Dutch Adult Reading Test (DART) is described. The DART is the Dutch version of the National Adult Reading Test. Both tests consist of a series of words with an irregular pronunciation. The score on the test is a predictor of premorbid intelligence of brain damaged patients. Furthermore, results of reliability and validation studies with the DART are reported. The main findings, which were obtained with the NART, were replicated by the DART. These findings consist of a high correlation (.85) with verbal intelligence in healthy controls (n = 22) and insensitivity to cerebral deterioration in brain damaged and demented patients (n = 53). The test also appeared to be insensitive to cognitive deterioration in a group of psychotic patients (n = 43). PMID- 1877069 TI - ['Dementia' and 'memory' in daily and weekly publications: an analysis of newspaper clippings in the period 1987-1990]. AB - Government, scientists and health care workers show an increasing interest in dementia and memory defects. It is unclear, however, whether the general public has acquired more access to the increased knowledge in this field. This is important to know because many people seem to worry about memory dysfunctions or about a possible dementia. An analysis of newspaper articles over a period of 3 years (March 1987 until March 1990) shows that the number of newspaper articles on memory has decreased. On the other hand, the average number of articles on dementia has increased from 11 per month in the first year to 25 and 28 in the second and third year. In these articles, most attention is given to research on dementia and to health care services for dementia patients. The number of articles on general aspects of dementia remained practically unchanged, although these articles in particular have an important informative function. In national newspapers, the attention for the six different themes is unequally divided. The themes 'general aspects of dementia', 'health care services' and 'research on dementia' have a relatively high impact. Finally, it appears that the same headline of an article can evoke different emotional reactions in a group of judges. Taking the results of this research into account, the authors argue that more health education activities should be directed at memory defects and dementia. Furthermore they conclude that a more systematic evaluation of these activities is necessary. PMID- 1877070 TI - [Home food services for the elderly: the consumer and his appreciation of a warm meal service in Arnhem]. AB - An important instrument to achieve prolonged independence of elderly is the provision of meals, in particular cooked meals at home. The purpose of the present study is an evaluation from the consumers perspective of a meals-on wheels service in Arnhem. Furthermore, the 77 meals-on-wheels consumers in this study, all making intensive use of the service, are described and compared to a representative sample of elderly. The participants appeared to be vulnerable from the perspective of health (particularly the women) and social situation. The perceived quality of both meals and service seem to be high. The taste, the quality of the meat and the first impression of the meal are important determinants of overall perceived meal quality. Responsiveness and reliability have a significant contribution to perceived service quality. PMID- 1877071 TI - [Social skills of the elderly, a cross-sectional study]. AB - A previous review of the literature showed that the elderly are expected to be less skillful in social situations than the young. This hypothesis is supported by two cross-sectional studies. Here it is tested in two ways. First the social skills of a stratified sample of 300 subjects (150 men and 150 women, evenly distributed over the age-range 56-85 years) were measured by self-report questionnaires, and compared to those of younger norm groups. The response was 45%. Secondly the relationship between social skills and age was examined within the group of elderly subjects. Both parts of the study showed results that were incompatible with the hypothesis. The elderly did not prove less skillful than the young, and no negative correlation between age and social skills was found within the research group. Contrary to the hypothesis, the elderly tended to be less anxious in social situations than the young. It is concluded that differences in social skills are much greater within, than between, age-groups. PMID- 1877072 TI - [Planning ability of older and younger adults]. AB - This investigation was aimed at the effects of ageing on planning. The investigation was carried out with young adults, middle-aged adults and elderly. Because of a suggested resemblance of problems described in elderly with impairments in patients with prefrontal cortical damage, and because the prefrontal cortex is important for planning, a test specifically sensitive to planning deficits in left prefrontal patients, the Tower of London test, was administered. On this test, the elderly solved significantly less problems in the allotted time than the two younger groups. However, the elderly did not show the same type of problem as that described in prefrontal patients. Such patients perform significantly worse on first attempts (problems correctly solved in one attempt). On this variable the elderly in our study equalled the younger adults in performance. However, they less often succeeded when the first attempt was not correct. To check whether this result could be explained simply by decreased mental and psychomotor speed and visuo-spatial function, regression functions between age and Tower score were computed, partialing out scores on tests of these more elementary abilities. A significant effect of age remained, which we tentatively interpret as an effect on planning ability. PMID- 1877073 TI - Perioperative nursing: moral and ethical issues in high--technology practice. AB - The caring component of perioperative nursing practice entails responsibility and accountability for nurses to identify and address the moral/ethical issues inherent in the practice. Ethical/moral issues in perioperative nursing are becoming more complex as technology becomes more sophisticated, financial resources become more restricted, and choices regarding care occur in an ambiguous environment. The practice environment must provide processes by which nurses can examine the ethical/moral choices made or to be made both to support the nurse and to increase the body of knowledge of perioperative nursing practice. PMID- 1877074 TI - Lasers and OR nursing: directions for the future. Nurse round table discussion. PMID- 1877075 TI - Being an effective speaker. AB - Communication in a group is an essential quality for success in nursing. Despite this, many nurses who must have communication skills to advance have little training in public speaking. Some nurses seek to correct such deficiencies in their education by taking courses in the evenings or on weekends to improve their understanding of the elements of effective speaking. Other nurses learn by self reflection, study, and ongoing practice. This article has presented guidelines for speaking in a group that can offer assistance in mastering this important nursing skill. Elements of nonverbal communication are crucial for effective communication. However, despite the importance of non-verbal communication to the message, language is what makes communication possible. It is language that allows people to communicate new ideas and thoughts and to solve problems. PMID- 1877076 TI - Malpractice and the National Practitioner Data Bank: what OR nurses need to know. AB - The National Practitioner Data Bank will record any payments made for any reason related to a malpractice suit in a central data bank available to a number of designated parties. Hospitals will be required to request this information to screen applicants and at least every 2 years for appointment renewals. The data bank may also be consulted by hospitals and state licensing boards as they deem necessary and by professional societies when reviewing membership applications. It is in the best interests of all malpractice defendants to insist on adequate representation of their personal, professional, and financial interests, which may necessitate insurance carriers providing each defendant with individual counsel. PMID- 1877077 TI - Puerile respiration: Laennec's stethoscope and the physiology of breathing. PMID- 1877078 TI - Elisha Kent Kane, M.D., U.S.N., 1820-1857. PMID- 1877079 TI - Rising stars: Carl G. Jung and astrology. PMID- 1877080 TI - Elisha Kent Kane's unpublished treatise on dropsy. PMID- 1877081 TI - Rockefeller Foundation fellowships in the humanities. PMID- 1877082 TI - Memoir of Francis C. Wood, 1901-1990. PMID- 1877083 TI - Francis Clark Wood: his contributions to medical science, 1901-1990. PMID- 1877084 TI - Memoir of John Perry Hubbard, 1903-1990. PMID- 1877085 TI - Memoir of Arthur M. Dannenberg, Sr., 1891-1990. PMID- 1877086 TI - Strategies for coping with low environmental temperatures. PMID- 1877087 TI - Restricted diffusion in photosynthetic membranes. AB - The structural organization of membrane proteins and their linkage by diffusion are topics of much debate. Functional studies in photosynthetic membranes, where rapid equilibration of electron transport between redox centers appears restricted to isolated domains, shed new light on the subject. PMID- 1877088 TI - Is hsp70 the cellular thermometer? AB - Cells respond to an increase in temperature by inducing the synthesis of the heat shock proteins, which are a small set of evolutionarily conserved proteins. We review the evidence leading us to suggest that the free pool of one of these proteins, hsp70, serves as a cellular thermometer that regulates the expression of all heat shock proteins. PMID- 1877089 TI - Molecular studies in Alzheimer's disease. AB - In the past decade, there has been an explosion of information relating to the molecular neurobiology of Alzheimer's disease (AD). Molecular dissection of the neuropathology of AD has provided insight into the pathogenesis of this disease and has defined areas where investigation may prove useful in elucidating the cause of this disorder and suggest new treatments. PMID- 1877090 TI - Photosynthetic reaction centers: interfacing molecular genetics and optical spectroscopy. AB - In the elucidation of the mechanism by which certain photosynthetic bacteria convert light into chemical energy, genetics has become intertwined with biophysical techniques. While X-ray crystallography has yielded an atomic resolution structure of the photosynthetic reaction center (RC), optical spectroscopy remains the most important technique for screening mutants. Newly developed imaging devices and genetic techniques should enable biophysicists to characterize rapidly the spectra of extremely large numbers of RC and light harvesting (LH) antennae mutants. The intrinsic pigments of the RC and LH antennae act as spectroscopic reporters for assembly and function of these integral membrane proteins. To optimize this genetics/spectroscopy interface, new algorithms that relate the structure of the genetic code to the physico-chemical properties of the amino acids are being developed to design libraries of mutants. PMID- 1877091 TI - Cell-penetrating inhibitors of calpain. AB - Inhibitors of the calcium-dependent cysteine protease calpain are described that are new analogs of the naturally-occurring compounds E-64 and leupeptin. These new derivatives, unlike the parent compounds, can inhibit calpain within cells. Their lack of charged groups probably accounts for this improved membrane permeability. These new inhibitors are proving useful in exploration of the role of calpain in many cellular processes, including platelet activation. PMID- 1877092 TI - Recognition of nascent polypeptides for targeting and folding. AB - A major difference between the refolding of proteins in vitro and the in vivo folding process, in which we include localization and assembly, is the need for additional factors in vivo, apart from the protein product itself. Thus, the amino acid sequence of a naturally selected protein contains not only the information specifying its three-dimensional structure, but also the information that enables these factors to recognize the nascent polypeptide. In this review, we consider how this latter information may be encoded and, in turn, interpreted by binding species. PMID- 1877093 TI - [Unstable fractures of the lateral end of the clavicle and principles of their treatment]. AB - 25 fractures of the lateral end of the clavicle were treated during the last six years. 22 of them were unstable because of additional rupture of the coracoclavicular ligaments. Only in two patients conservative treatment was successful, in six cases conservative treatment was unsuccessful. Altogether 20 fractures had to be operated. Coracoclavicular screw fixation (Bosworth) is recommended for simple fractures and plating for multifragmental injuries. Operative methods using K-wires are frequently impaired by wire-migration and therefore require a longer period of external immobilization. Independent of the type of surgery objective and subjective results were equally good. PMID- 1877094 TI - [Treatment of acromioclavicular dislocations by a pin and tension band fixation]. AB - Dislocations of the acromioclavicular joint are common injuries in sports and traffic accidents. The most widely used classification of these injuries is the one of Tossy, Tossy III and Tossy II injuries are indications for operative treatment. Among several different surgical approaches a very common procedure is the temporary fixation of the AC-joint by two pins, tendon band wiring and suturing of the ligaments. Recently we have been using a temporary transfixation by only one pin, tension band fixation with PDS and suturing of the ligaments. The advantages of this method are: preservation of clavicular rotation, easier operation and metal removal, and less damage of the joint cavity. Results and complications are presented. PMID- 1877095 TI - [Variable head endoprosthesis in the treatment of femoral neck and trochanteric fractures]. AB - During 1978 to 1987 361 patients (312 female, 49 male) were treated with Variokopf-prosthesis (a bipolar hip prosthesis with a variable head) after femoral neck fracture, per- or subtrochanteric fracture. The mean age was 83 years. During postoperative treatment 73 patients (20.2%) died. 288 could be discharged. 98 of these died before the follow-up examination. The follow-up was possible in 103 cases. A good to satisfactory result was found in 91 cases (88%). A poor result in twelve cases (12%) (Score by Merle d'Aubigne et al.). CONCLUSIONS: 1. The Variokopf-prosthesis is a favourable alternative to a normal hip prosthesis (e.g. Moore), 2. The implantation of a Variokopf-prosthesis was found to be indicated as well in the treatment of medial femoral neck fractures as in special cases in the treatment of per- or subtrochanteric fractures. 3. The operation should be performed soon after the trauma--after a two to three days treatment. 4. The dorsal approach is superior to the lateral in the treatment of hip fractures because of short operating time and the possible early mobilisation of the patients. PMID- 1877096 TI - [Experience with Ender nailing in 671 cases]. AB - Between 1976 and 1987 at the Surgical Department of the University of Erlangen Nurnberg, 671 fractures of the trochanteric region of the femur were treated by Ender nailing. In 54 cases (8.0%) there were intraoperative complications, in 82 cases (12.2%) postoperative complications occurred. Reoperation became necessary at 57 (8.5%) patients. Because of this complication rate we only see indications for Ender nailing in patients with skin lesions over the fracture site, valgus angulation of the proximal fragment and in the palliative treatment of pathological fractures. PMID- 1877097 TI - [Ender nailing--an attempt at determining the position]. AB - Fractures of the coxal end of the femur at first are strained by bending because of appearing compressive and tractional forces. Only second torsion and shearing forces have their effects on the feature of the fracture. In operative treatment of fractures near hip-joint this kind of implant is the best, which mostly is corresponding to the physiological flow of force, according to the anatomic conditions. The more a method brings these conditions, the earlier the fracture and with it the patient can be charged again. The Ender-nail largely fulfills these conditions by its axial position in the field of force and its elastic fixation in the femur shaft. We report about our own experiences in 346 cases using the Ender-nail. PMID- 1877098 TI - [Clinical results of Palmer's primary cruciate ligament insertion without augmentation]. AB - The clinical importance of primary cruciate ligament reconstruction without augmentation-plasty is discussed on the background of long term results following 51 operations. Based on standardized methods of evaluation 38 patients had a very good and good result, in eleven cases the operation lead to a fair and in two cases to a poor result. A significant instability with a pivot shift grade III was recorded in two cases: twelve patients showed a low degree of instability whereas 37 patients had regained full stability. The coincidence of a cruciate ligament lesion and a rupture of a collateral ligament had a negative influence on the postoperative long term result (p less than 0.01). Our results suggest that a primary repair without augmentation-plasty is a qualified procedure for stabilizing the knee joint in cases with an acute femoral rupture without accompanying collateral lesions. In patients with old ruptures or a complex joint lesion primary repair with augmentation is recommended. PMID- 1877099 TI - [The place of bundle nailing in the surgical treatment of fractures of the shin bones]. AB - Authors report about their good experiences with the tibia bundle-nailing during 23 years' patient-material on the Traumatological Department of the Hospital in Eger/Hungary comparing to other osteosynthesis methods. They report about their operative technic, the indications, post-operative treatment and analyse their results. In connection with operative treatment of 251 patients with this method they emphasize that the bundle-nailing of Hackethal is by correct indication a method of tried integrity in these days, too. PMID- 1877100 TI - [Electronic data processing in the hospital: current status, options, "branch packets", customer-specific software and users' needs]. AB - Data management in hospitals used to be the data management of the hospital management in the last 15 years, not however the data management the doctors performed. The acceptance for electronic means slowly rising more software is used in the clinics today but still by the doctors privately. Software specialists have registered the growing market available for their products. That is why the danger to accept even unusuable software rises every day, as unexperienced software-beginners as doctors mostly are often relied on offers without being told about their dignity and usefulness. PMID- 1877101 TI - Urologic oncology. A festschrift for Dr. Willet F. Whitmore, Jr. PMID- 1877102 TI - Role of lymphadenectomy in renal cell carcinoma. AB - A hilar or limited lymph node dissection will not remove the primary lymphatic drainage area of either kidney. For a lymphadenectomy to have a therapeutic benefit, an extended dissection is required, particularly for right-sided tumors. An extended lymphadenectomy may not be justified in all patients with renal cell carcinoma, particularly those with small tumors (who rarely have lymphatic disease) or grossly positive nodes (who have a high risk of existing distant metastases). For some patients with T3 or V+ tumors and palpably normal retroperitoneal nodes, an extended nodal dissection may resect microscopically involved nodes and result in an improved survival rate. This hypothesis will not be tested appropriately until a randomized controlled study is performed. PMID- 1877103 TI - The incidental renal mass. Management alternatives. AB - The problem of the incidental renal mass will confront all urologists with increasing regularity, and no universal strategy can be employed. Complete excision of the mass, including a margin of normal tissue, may be adequate therapy if a cancer is present and will preserve renal parenchyma if the lesion is benign. Care must be taken not to stretch the limits of this approach. Larger lesions (greater than 3-4 cm) are likely to be cancer and are better treated with a nephrectomy. While this management philosophy is logical and appealing, it has not been validated by clinical experience, and caution must still be exercised. PMID- 1877104 TI - Inferior vena caval involvement by renal cell carcinoma. Use of venovenous bypass as adjunct during resection. AB - Venovenous bypass allows the safe conduct of operation during resection of renal cell carcinoma with inferior vena caval involvement by allowing venous return when the inferior vena cava is clamped, thus preventing hypotension. It obviates the heparin required for full cardiopulmonary bypass and therefore decreases postoperative bleeding. A blood retrieval system decreases the volume of banked blood required. A Moretz clip placed early on the intrapericardial inferior vena cava allows adequate venous return and prevents a massive pulmonary tumor embolism. PMID- 1877105 TI - Management of renal cell carcinoma with vena caval thrombi via cardiopulmonary bypass and deep hypothermic circulatory arrest. AB - Cardiopulmonary bypass with deep hypothermic circulatory arrest allows safe and effective removal of renal tumors with extensive thrombi involving the vena cava under controlled circumstances without permanent side effects. The technique averts extensive dissection of the inferior vena cava and occlusion of major vessels while providing up to 60 minutes of safe operating time in a bloodless field and complete visibility of the interior of the vena cava. Adjunctive procedures for tumor excision or cardiac revascularization can be performed at the same time without increased operative risk. PMID- 1877106 TI - Accuracy of imaging modalities in staging the local extent of prostate cancer. AB - In this study, none of the evaluated clinical staging methods was found to predict reliably the presence or absence of extracapsular growth of histologically proved carcinoma of the prostate. In this respect, digital rectal examination, transrectal ultrasound, CT, and MR imaging cannot contribute to treatment decisions in localized prostate cancer. Further studies are under way to determine the value of 7.5-MHz scanners in transrectal ultrasound and high resolution surface coils in MR imaging. PMID- 1877107 TI - Digital rectal examination and carcinoma of the prostate. AB - Urologists have considered themselves to be the experts in the use of digital rectal examination for the evaluation of diseases of the prostate. However, without close attention to the teaching of this examination, it probably is inaccurate and unreliable. Moreover, many patients who are destined to die of prostate cancer never develop a palpable abnormality. In patients with prostate cancer, a palpable abnormality usually indicates the presence of carcinoma, but the majority of patients will be upstaged by pathologic examination. In patients undergoing a digitally guided biopsy, it appears critical that those with a negative biopsy be followed closely, as they have a measurable risk of developing overt carcinoma. It is unclear how transrectal ultrasound will interface with digital rectal examination because of the multiple echo patterns this disease can exhibit. PMID- 1877108 TI - Long-term follow-up after radical prostatectomy. Identification of prognostic variables. AB - We report one of the largest series of patients treated by radical prostatectomy followed for a minimum of 10 years. The tumor-free survival rate at 10 years seems superior to that achieved with alternative methods of treatment. Pathologic stage, DNA histograms, and tumor grade all correlate with prognosis but none is sufficiently powerful as an independent factor to allow selection of patients for surgery. Although a survival benefit has not been demonstrated, adjuvant treatment such as postoperative irradiation or early hormonal therapy may be indicated in patients with established poor prognostic factors. PMID- 1877109 TI - Is combined modality therapy appropriate for apparently localized carcinoma of the prostate? AB - In a pilot study at the authors' institution, 17 patients with stage C carcinoma of the prostate had preoperative therapy with diethylstilbestrol. After 8 to 12 weeks of DES at 3 mg per day, the surgical margins, seminal vesicles, and pelvic lymph nodes were free of tumor in seven patients. In one patient, no residual tumor could be found despite an extensive search, and in two other cases, only small foci of atypical cells could be found. The authors suggest a trial of the proper role of neoadjuvant hormonal therapy in stages B2 and C prostatic carcinoma. PMID- 1877110 TI - Iridium-192 brachytherapy in the treatment of cancer of the prostate. AB - Aggressive radiotherapy was used in 170 patients with advanced localized carcinoma of the prostate. After pelvic lymphadenectomy, 192Ir brachytherapy was used to deliver 3500 cGy to the prostate within 2 days. External-beam therapy (4500 cGy) was then given to a total of 8000 cGy. Random biopsies 18 months afterward were negative for residual cancer in 62 of 83 patients (75%), and 37 of 45 patients (82%) with pathologically proved localized disease remain without evidence of disease. Morbidity was significantly reduced in the most recent 70 patients by improvements in technique. The authors believe such therapy should be considered for patients with advanced stage B2 or C disease in particular. PMID- 1877111 TI - Local failure after definitive radiation or surgical therapy for carcinoma of the prostate and options for prevention and therapy. AB - The incidence of local failure and its relation to distant failure following definitive therapy of carcinoma of the prostate is discussed. Local failure may arise from incomplete resection, tumor spillage, clones of radioresistant cells, development of new tumors in an organ left in situ, or inadequate treatment portals. The authors review the various measures used as prophylaxis or treatment of local failure in relation to clinical and pathologic stage. PMID- 1877112 TI - Environmental and nutritional factors significantly associated with cancer of the urinary tract among different ethnic groups. AB - A high incidence rate of urinary tract cancer in the Acre District among the Jewish population compared with the non-Jewish population has been studied. The dietary and environmental factors identified and the possible mechanisms of the protective effect that may be conferred by fluid intake, olives and olive oil, cumin, and pepper (chili pepper and pepper) are discussed. PMID- 1877113 TI - Evaluation of a new bladder tumor marker. AB - Two monoclonal antibodies have been developed that bind to a shed bladder tumor associated antigen. Preliminary data have demonstrated that antigen-positive tumors shed detectable amounts of antigen in the urine while antigen-negative tumors do not. This antigen may be differentially metabolized by normal and malignant urothelial cells. Further characterization of this antigen and its evaluation as a urinary marker for antigen positive bladder cancers is continuing. PMID- 1877114 TI - Molecular and immunologic approaches in the management of bladder cancer. AB - Because of the heterogeneous nature of bladder cancer and the various therapeutic options available, the management of the disease is a constant challenge to clinicians. A variety of new biologic approaches are beginning to unravel some of the pathophysiology underlying the behavior of these tumors and provide means to assess it at the clinical level. Monoclonal antibodies are particularly well suited for more immediate application as diagnostic and prognostic tools and may also have an impact on the treatment of patients with bladder cancer. PMID- 1877115 TI - Transurethral resection and intravesical therapy of superficial bladder tumors. AB - The treatment of superficial bladder cancer is aimed at eradicating existing disease, inhibiting tumor recurrence, and preventing progression to invasion or metastasis. Transurethral resection is the primary modality, with intravesical therapy used in some cases to kill residual overt or occult carcinoma and premalignant lesions. Among the agents tested extensively, BCG appears to be more effective than mitomycin C, doxorubicin, or thiotepa, especially against carcinoma in situ. A number of questions remain to be answered about the management of this disease. PMID- 1877116 TI - Will Rogers and the results of radical cystectomy for invasive bladder cancer. AB - Disease-free survival rates for patients with muscle-invasive bladder cancer treated by radical cystectomy with bilateral pelvic lymphadenectomy with or without adjuvant chemotherapy are 75% to 80% in stage B disease, 60% in stage C disease, and approximately 50% in stage D disease. Vascular invasion is an important prognostic factor in meticulously staged patients. Powerful selection factors, including more accurate clinical and pathologic staging and improved surgery, as well as unspecified selection factors, may contribute to the improved results. In order to evaluate the impact of adjuvant chemotherapy, a randomized, controlled study is necessary. PMID- 1877117 TI - Neoadjuvant therapy in invasive bladder cancer. Problems and pitfalls. AB - It is clear that some transitional-cell tumors of the bladder will respond to combined therapy. However, in the absence of randomized controlled trials, the impact of repeated transurethral resections versus the effect of chemotherapy cannot be assessed adequately, and such trials are urgently needed before neoadjuvant therapy can be considered standard. In addition, newer chemotherapy agents or the combination of currently available drugs with the addition of hematopoietic growth factors such as granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor to reduce toxicity and permit dose intensification in an attempt to increase overall response rates offer fruitful avenues for clinical research. Although cisplatin-based chemotherapy obviously does not have the same impact on bladder cancer that it does on testicular cancer, the initial results are encouraging. The "wall" has been breached, and the demonstration that urothelial tumors can be added to the list of chemotherapeutically responsive tumors should encourage urologic, radiologic, and medical oncologists to combine efforts in randomized, controlled studies of integrated approaches to therapy. PMID- 1877118 TI - Preoperative and postoperative adjuvant chemotherapy using CISCA (cyclophosphamide, doxorubicin, and cisplatin) in the treatment of invasive transitional-cell carcinoma of the bladder. AB - Fifteen patients with invasive (T2-T4) transitional-cell carcinoma of the bladder were scheduled for three courses of CISCA followed by radical cystectomy and two additional courses of CISCA. Seven patients completed the entire protocol, and 13 completed all the preoperative courses. Seven of 13 patients demonstrated downstaging of their cancers. Of these patients, one has died, one is alive with disease, and five are free of disease at 7 to 38 (mean 17) months. Of the six patients without downstaging, one survives free of disease at 42 months and one is alive with disease 12 months after cystectomy. Downstaging appears to be an important prognostic indicator. Additional studies are being conducted to determine if neoadjuvant chemotherapy improves long-term survival. PMID- 1877119 TI - Interval report of a phase I-II study utilizing multiple modalities in the treatment of invasive bladder cancer. A bladder-sparing trial. AB - Clinicians at the Massachusetts General Hospital have used two cycles of methotrexate, cisplatin, and vinblastine (MCV) before radiotherapy and cisplatin in 53 patients with muscle-invasive bladder cancer. Eleven patients did not complete the protocol, but overall, the toxicity was not formidable. Of the total patients accessioned, 34 are alive. Of the 34 patients in the series who completed the full treatment protocol, the estimated survival rate at 54 months is 77%. This interim analysis suggests that the treatment is achieving at least limited success in saving lives and bladders. PMID- 1877120 TI - The ileal neobladder. AB - The ileal neobladder in many respects approximates the theoretically ideal continent urinary diversion. The technique, while more technically demanding than the performance of the standard ileal loop diversion, is not difficult, particularly for surgeons used to performing radical retropubic prostatectomies. The ileal neobladder appears to approximate most closely the optimal bladder substitution. Although currently feasible only in males, future considerations could conceivably involve urologists working with their colleagues in gynecology and colorectal surgery to extend the benefits of bladder substitution using the ileal neobladder to selected patients having cystectomy for associated gynecologic or colorectal malignancies. PMID- 1877121 TI - Genitourinary rhabdomyosarcoma in children. AB - The survival rates for childhood rhabdomyosarcomas have risen from 20% to 50% with the institution of a multidisciplinary approach involving the pediatric oncologist, radiation therapist, and surgeon. Increased survival has been particularly striking in the case of genitourinary rhabdomyosarcomas, which have a more favorable prognosis than rhabdomyosarcomas occurring in other anatomic sites. By stratifying genitourinary rhabdomyosarcomas by anatomic subgroup, i.e., paratesticular, bladder or bladder-prostate, and gynecologic, insight into specific predictors of failure can be obtained. Patients judged to be high risk at diagnosis can then be selected for more intensive or novel forms of therapy. PMID- 1877122 TI - Urologic sarcoma in adults. Memorial Sloan-Kettering Cancer Center experience based on a prospective database between 1982 and 1989. AB - Urologic sarcoma is a group of rare tumors with a generally poor prognosis. These sarcomas share prognostic characteristics with soft-tissue sarcomas arising from other sites. A staging system that incorporates tumor grade and size is valuable in identifying patients at high risk of dying of disease. Patients with sarcomas that are high-grade, greater than 5 cm in diameter, or metastatic at the time of presentation (MSKCC stages 3 and 4) have a combined 3-year relapse-free survival rate of 26%. Complete surgical resection, preferably with negative margins, still offers the best chance of cure. For reasons that are not clear, multimodality therapy in rhabdomyosarcoma is less effective in adult than in pediatric disease. Present-day chemotherapeutic regimens are ineffective in controlling disseminated sarcoma. The adoption of a uniform staging system coupled with multi institutional collaboration may allow progress to be made in this otherwise deadly form of genitourinary cancer. PMID- 1877123 TI - [43rd meeting of the German Society for Urology. Berlin, 18-21 September 1991. Abstracts]. PMID- 1877124 TI - Digitally-directed transrectal biopsy using Biopty gun versus transrectal needle aspiration: comparison of diagnostic yield and comfort. AB - A technique for digitally-directed core biopsy using the Biopty device and prospective comparison of accuracy and comfort, using this technique simultaneously with transrectal needle aspiration, are presented. To better estimate the true prevalence of carcinoma in the study population, a repeat combined procedure was performed on all subjects who did not have carcinoma confirmed on the initial core biopsies. All procedures were done by one investigator and all pathology reviewed by one senior pathologist. A total of 180 combined procedures were performed on 100 consecutive patients with palpably abnormal prostates; 30 carcinomas were detected. Digitally-directed Biopty biopsy yielded a sensitivity rate of 87 percent compared with 57 percent for needle aspiration (p less than 0.05). Using a numerical comfort scale, the Biopty device was also rated less painful than needle aspiration (p = 0.0001). The morbidity of the combined procedure was minimal, with a minor complication rate of 2.2 percent. No infections occurred. PMID- 1877125 TI - Polytetrafluoroethylene vs. polypropylene suture for endoscopic bladder neck suspension. AB - Between May 1989 and October 1989, 24 women underwent a prospective, randomized study comparing polypropylene (Prolene) and polytetrafluoroethylene (Gore-Tex) sutures for endoscopic bladder neck suspension. Polypropylene was associated with significantly more suture pain than polytetrafluoroethylene. Polytetrafluoroethylene was more difficult to tie at a predetermined tension. PMID- 1877126 TI - Application of smooth Teflon clip to inferior vena cava during radical cystectomy to prevent postoperative pulmonary embolism. AB - Between 1976-1986, a smooth Teflon clip was applied to the inferior vena cava of 56 patients who underwent radical cystectomy for bladder cancer. The purpose of the clip is to narrow the lumen of the inferior vena cava so that large emboli will be trapped and thus prevented from reaching the lungs. These 56 patients were compared with a group of 26 historical controls who underwent radical cystectomy without application of such a clip between 1967-1976. One patient (1.8%) whose vena cava was clipped had a pulmonary embolus which was fatal. Four (15.4%) of the 26 control patients had postoperative pulmonary emboli, the embolic event being fatal in 3 (11.5%). Application of the smooth Teflon clip to the inferior vena cava significantly lessens the incidence of pulmonary embolism following radical cystectomy. PMID- 1877127 TI - Urinary incontinence volume patterns in elderly inpatient men. AB - Urinary incontinence is a costly and debilitating disease of the aged. Although the most common clinical finding is detrusor hyperreflexia on filling cystometry, the role of this urodynamic abnormality in the etiology of incontinence is uncertain. The purpose of this study was to evaluate elderly patients who have cystometric detrusor hyperreflexia and to determine the incontinence volume characteristics of these patients during regular daily activities. Ten patients with detrusor hyperreflexia during filling cystometry and an incontinence volume level above 1 L per day were evaluated according to the volume of urine loss per incontinence episode during a ten-day measurement period. All patients studied were found to have an irregular urinary incontinence volume distribution with a wide range of involuntary urine loss per incontinence episode. An irregular pattern of incontinence volume was found in each patient which suggests that detrusor hyperreflexia is manifest as an irregular involuntary loss of urine during daily activities of elderly inpatients. This unstable bladder activity relative to the volume of urine loss appears to be an important factor in the pathophysiology of urinary incontinence in aged inpatients. PMID- 1877128 TI - Metabolic changes in patients undergoing right colon continent urinary pouch diversion. AB - The concept of continent urinary diversion is undergoing re-evaluation now that a stable continent valve can be produced with certainty. The right colon pouch consists of the distal 6 inches of the terminal ileum, the cecum, ascending colon, and proximal third of the transverse colon, and has a volume of up to 1,200 mL. The present study investigates the electrolyte changes that occur when urine is held in the pouch for increasing lengths of time. No significant changes in serum electrolytes occurred with catheterization intervals up to six hours in a group of patients that were studied for an excess of six months. PMID- 1877129 TI - Macroscopic vasovasostomy re-examined. AB - Results of 273 consecutive macroscopic vasovasostomy procedures performed at a single institution over a nine-year period between 1978 and 1987 were reviewed. When patients operated on less than five years after vasectomy were compared with those in whom more than five years had elapsed since vasectomy, significant declines in technical success rates as measured by return of sperm to the ejaculate (93% vs. 74%, p less than 0.004), biologic recovery as measured by mean sperm counts (55 million vs. 35 million) and mean progressive sperm motility (30% vs. 13%), and clinical success as measured by pregnancy rates (52% vs. 30%, p less than 0.02), were observed. Examination of complications of vasovasostomy showed a 7.7 percent overall complication rate and a 1.5 percent incidence of major complications. PMID- 1877131 TI - Anterior urethral polyp associated with hematuria in six-year-old child. AB - Anterior urethral polyps are rare, occur only in male patients, and have been associated with obstruction, terminal hematuria, and enuresis. We believe this is the fifth reported case of anterior urethral polyp associated with terminal hematuria. The radiographic findings, treatment, and pathology are reviewed. PMID- 1877130 TI - Enuresis and the voiding cystourethrogram: a re-evaluation. AB - Eighty-three children with a chief complaint of nocturnal enuresis and no history of urinary tract infection (UTI) were prospectively evaluated with a contrast voiding cystourethrogram (VCUG). The following four historical details of presentation were noted: primary vs. secondary enuresis, daytime wetting, urgency, and frequency. Each of these four symptoms were treated as a dichotomous variable, and the prognostic value with respect to vesicoureteral (VUR) reflux was assessed using a linear logistic regression model. Nineteen ureters in 13 patients (16%) demonstrated VUR: grade I, 7 ureters; grade II, 5 ureters; grade III, 3 ureters; grade IV, 4 ureters; and grade V, 0 ureters. Three patients demonstrated renal scarring (16%) and 2 patients underwent surgery. The linear regression analysis revealed that no one symptom, group of symptoms, or absence of all four symptoms segregated those patients likely to have reflux with statistical validity. One of 6 children, therefore, who present with nocturnal enuresis and sterile urine will have reflux. Screening these children with a VCUG should be considered. PMID- 1877132 TI - Treatment of staghorn calculi with extracorporeal shock-wave lithotripsy and percutaneous nephrolithotomy. AB - Between August 1983 and August 1987, 72 staghorn calculi were treated in 66 patients. Treatment was with percutaneous nephrolithotomy (PCNL) in 30, extracorporeal shock-wave lithotripsy (ESWL) in 18, combination PCNL-ESWL in 23, and nephrectomy in 1. Complications occurred in 59 percent of patients and were twice as common after PCNL as after ESWL. Radiologic follow-up on 69 kidneys (97%) showed 58 percent were stone-free, 15 percent had residual sand or matchheads less than 5 mm, 17 percent had residual fragments of 5-15 mm, and 10 percent had greater than 15 mm residual stone burden. With a mean follow-up of thirty months, 2 of 40 stone-free patients had persistent asymptomatic Proteus urinary tract infections, and 4 of 22 patients with residual calculi less than or equal to 15 mm required additional operative treatment. PMID- 1877134 TI - Effect of occluding the urethra while recording urethral stress profile. AB - The correlation between clinical and tonometric incontinence is frequently poor, with urethral profile results that do not correspond to clinical reality. Among potential causal factors, we have attempted to determine the importance of the absorption of kinetic energy from the mass of urine driven against the urethral captor (the hydraulic ram effect). Twenty patients (average age 50 +/- 10 years, para 2) suffering from genuine stress urinary incontinence, underwent urodynamic investigation with a constant air-flow pneumatic catheter equipped with two captors separated by an inflatable cuff located just above the urethral captor to block the inrush of urine into the urethra. After cystometric examination had excluded an unstable bladder, two urethral profiles were registered successively, first with cuff deflated, and then with cuff inflated. The values for urethral functional length (FL) and transmission factor (TF) show no significant changes. The values for the maximal urethral closing pressure (MUCP) were significantly lower in the second profile (cuff inflated) in 18 of 20 cases (average decrease 7 cm H2O), which corresponds to 14 percent of the average MUCP measured during the first profile (cuff deflated). The depression quotient increased from an average 0.80 to 1.05 from first to second profile. This study allows quantification of the urethral "hydraulic ram effect" which modifies determination of the MUCP during registration of urinary stress profile. PMID- 1877133 TI - Extracorporeal shock-wave lithotripsy in patients with spinal cord dysfunction. AB - Patients with spinal cord dysfunction are at an increased risk for urolithiasis. A retrospective study was undertaken to determine the effectiveness of extracorporeal shock-wave lithotripsy (ESWL) in this population. Thirteen kidneys received 19 treatments averaging 2,350 shocks per renal unit. All but one of the stones showed good fragmentation; however, none of the patients was stone-free at three months. Four of 9 patients with long-term follow-up were stone-free at five to fifteen months. Our poor stone-free rate is similar to that found in other studies of patients with spinal cord dysfunction. ESWL was well tolerated in this population, however, the clearance of stones is poor and delayed. PMID- 1877135 TI - Digital-directed transrectal core biopsy with spring-loaded biopsy device (Biopty). PMID- 1877136 TI - Immunohistochemical staining of CA 50 antigen in human bladder cancer. Relation to histologic grade, clinical stage, and prognosis. AB - The immunohistochemical detection of tumor marker CA 50 was studied in bladder cancer of WHO grades I-III. The material consisted of tumors in 83 patients and the mean clinical follow-up time was thirteen years (range 9.6-22 years). The fraction of CA 50-positive cells (FPtot) in microscopic image was scored 0-100 percent. Also the maximally staining region was selected, and the fraction of CA 50-positive cells in this region was scored 0-100 percent (FPmax). The average staining intensity of CA 50-positive cells was scored from 0 to 3 in the whole section (ASItot) and in the maximally staining area (ASImax). The inverse relation between histologic grade, FPtot (p = 0.0001), and ASItot (p = 0.006) was statistically significant. FPtot (p = 0.039) and ASItot (p = 0.018) were also inversely related to clinical stage. Occurrence of metastasis during the follow up was associated with low CA 50 positivity (FPtot, p = 0.003; ASItot, p = 0.002). The lower the staining intensity or the lower the fraction of CA 50 positive cells, the more aggressive was the tumor. In survival analysis, low FPtot (p = 0.002) and ASItot (p = 0.007) values were related to high risk of bladder cancer death. The results show that immunohistochemical staining of bladder tumor specimens with CA 50 can be used to predict bladder cancer aggressiveness and survival. PMID- 1877137 TI - Diagnostic usefulness of post-void film in intravenous urogram. AB - A survey was sent to urologists to assess their subjective evaluation of the post void film in the intravenous urogram (IVU). Most of the urologists believed that the post-void film should be a routine part of all IVUs, particularly in men over forty years of age, and estimated that the film contributed useful information in 30 percent of cases. One hundred fifty IVUs were reviewed to assess the actual value of the post-void film in 119 different patients. In these patients, the postvoid film was seen to give unique information not available by history or films of the filled bladder in only 3 percent of the cases. Therefore, we conclude the post-void film should not be a routine part of every IVU, and should be obtained on an as-needed basis only. PMID- 1877138 TI - Fifty-six-year-old woman with flank pain and azotemia. PMID- 1877139 TI - Adrenal cortical carcinoma with vena cava tumor thrombus requiring cardiopulmonary bypass for resection. AB - We believe this is the fifteenth case report of adrenal cortical carcinoma with tumor thrombus to the vena cava, and the fourth reported case of a left-side tumor propagating thrombus to the vena cava. The patient underwent successful resection which required cardiopulmonary bypass. The caval tumor thrombus was very friable and gelatinous, unlike many renal cell thrombi, and required special surgical considerations. PMID- 1877140 TI - Gallbladder and pancreatic metastases from bilateral renal carcinoma presenting with hematobilia and anemia. AB - A case of bilateral metachronous renal cell carcinoma with gallbladder and pancreatic metastases, presenting with hematobilia and anemia is presented. The presentation of metastatic renal cell carcinoma with hematobilia and anemia is previously unreported. This case illustrates (1) the occasionally very long interval between metachronous renal carcinoma; (2) this tumor's propensity to unusual metastases and unpredictable presentation; and (3) the significant palliation which may be achieved by appropriate surgical resection of these metastases. PMID- 1877141 TI - Adrenal rest carcinoma in hilum of kidney. AB - Adrenocortical rests are uncommon in adults and infrequently undergo malignant changes. Most of the published cases are those of functional tumors allowing preoperative diagnosis on the basis of the resulting endocrinopathy. Most nonfunctioning tumors were found accidentally at operation or autopsy. A case is presented of a parapelvic nonfunctioning adrenocortical rest carcinoma situated in the renal hilus in a fifty-year-old woman. No such tumor has been described previously. PMID- 1877142 TI - Vas deferens abscess six years post vasectomy. PMID- 1877143 TI - Penetration of lomefloxacin into human prostatic tissue. PMID- 1877144 TI - Special applications in use of flexible cystoscope. PMID- 1877145 TI - Unsettled outlook for education. PMID- 1877146 TI - Veterinary medicine: the shape of things to come. PMID- 1877147 TI - History of the healing professions. PMID- 1877148 TI - Two hundred British veterinary years. PMID- 1877150 TI - Working together for excellence. PMID- 1877149 TI - A brief history of the schools. PMID- 1877151 TI - Veterinary education in the European Community. PMID- 1877152 TI - CPD and the universities: 2000 and beyond. PMID- 1877153 TI - New pig disease. PMID- 1877154 TI - Weak calf syndrome. PMID- 1877155 TI - [Ultrasound diagnosis of bile ducts after cholecystectomy]. AB - The paper is concerned with the results of multiprojectional ultrasound investigation of the biliferous system in 68 patients at varying time after cholecystectomy. In most cases (77.9%) signs of dilated biliary ducts were undetectable. Dilatation of the hepaticodoch was most frequently determined by choledolithiasis, stricture or stenosing papillitis, rarely--by pancreatic head cancer. Investigation of the biliary ducts in patients after cholecystectomy should be started with ultrasound tomography; endoscopic retrograde cholangiopancreatography or iv cholangiography and dynamic cholescintigraphy were indicated after the detection of the signs of dilated ducts (the anteroposterior diameter of the common hepatic duct was over 6 mm). PMID- 1877156 TI - [Computerized tomography of the mechanical jaundice in the involvement of the distal region of the common bile duct]. AB - Computerized tomography (CT) is a noninvasive indirect method of instrumental investigation for imaging the liver, bile ducts and the adjacent organs. CT enables one to confirm objectively the mechanical nature of jaundice, to assess a degree and level of involvement of the biliary tract, to assess the nature and spreading of disease. CT sensitivity for the diagnosis of pancreatic head cancer was 78.8%, specificity-91.3%, that for choledocholithiasis--84.6%, specificity- 96.7%. CT in jaundice made it possible to establish diagnosis at various levels of accuracy: from differentiation of mechanical and parenchymatous jaundices to preliminary assessment of malignant tumor resectability facilitating a choice of surgical tactics. PMID- 1877157 TI - [Computerized tomography in the differential diagnosis of biliopancreatoduodenal diseases]. AB - The paper is concerned with analysis of CT-investigation of 150 patients with diseases of the biliopancreatoduodenal area, whose diagnosis was verified histologically or by clinical observation over time, using other methods, (USI, RCPG, etc.). The authors have arrived at a conclusion that for increasing the informative value of CT one should use various methods of a contrast study of the duodenum and biliary tract, electron reconstruction of CT images in different projections. They have pointed out the most significant differential-diagnostic CT signs, proposed a table to facilitate the identification of causes and a level of obturation of the bile ducts, the table playing an important role in a choice of adequate therapy. PMID- 1877158 TI - [X-ray diagnosis of urinary tract diseases in genital endometriosis]. AB - The paper is concerned with the results of combined investigation of 157 women suffering from genital endometriosis, operated on for this disease. The involvement of the lower parts of the ureters in a pathological process was detected in 48 patients before operation and in 6 patients at operation. Comparison of x-ray and operative findings with histology specimens made it possible to define endogenous and exogenous forms of ureteral endometriosis and three variants of an x-ray picture in this pathology (the absence of abnormal changes of the urinary tract, hydroureter is over the narrowed part of the ureter, hydroureteronephrosis). The authors have shown a high informative value of combined x-ray investigation and the effectiveness of its use in clinical practice. PMID- 1877159 TI - [Computerized tomography in the diagnosis of asymptomatic renal cysts]. AB - The authors analyzed CT-data on 1732 patients aged 21 to 83 to detect symptom free renal cysts which were found in 30% of the patients. The rates and prevalence of symptom-free renal cysts were studied. A high resolution was noted. A majority of cysts was detected in patients over 50. The rates and prevalence of renal cysts testified to their low clinical significance (in the authors' opinion). PMID- 1877160 TI - [The role of computerized tomography in the diagnosis and evaluation of the dissemination of malignant kidney tumors]. AB - CT, performed in 66 patients with suspected renal tumors, showed renal cell carcinoma in 36. Tumor spreading was correctly established in 80.6%. Accurate diagnosis was made in 64 of 66 cases. The authors regard CT as an effective method for the recognition of sizable processes and differential diagnosis of solid tumors. Among the visual methods of investigation, used to define a tumor stage, CT turned out to be the most effective one. PMID- 1877161 TI - [Magnetic resonance tomography in the diagnosis of renovascular hypertension]. AB - MR tomography was used for investigation of 38 patients with renovascular hypertension (RVH) and 26 healthy persons. A possibility of the use and practical value of the method in the diagnosis and evaluation of renal function and renal arteries (RA) were under study. Some quantitative MRT indices were calculated both for the patients and healthy persons. They included spin-spin relaxation time, proton density, and signal intensity. These data can provide important information on renal function in RVH with relation to kidney sizes and the state of the renal parenchyma (evaluation of the cortical substance and medulla and the border between them). In some cases MRT ensures noninvasive diagnosis of PA stenosis. PMID- 1877162 TI - [Radioendovascular prosthesis of renal arteries in patients with renovascular hypertension]. AB - A high percentage of restenoses after roentgenovascular dilatation of the renal arteries laid the basis of a search for new therapeutic methods for these patients. Experiments on implantation of nitinol spiral endoprostheses showed their ability for long-term permeability of renal arteries, not causing their thrombosis and intimal spreading, destruction of formed elements of the blood, change in plasma proteins. Morphological investigations have shown rapid formation (during 14 days) of connective tissue neointima, covered on the side of the blood flow with the true vascular endothelium (ensuring a nonadhesive surface and laminar blood flow), around the coils of an endoprosthesis. This method after its experimental development started to be used in clinical practice. The authors reported the first experience in the clinical use of this method (12 patients with vasorenal hypertension). A 15-month follow-up revealed a stable antihypertensive effect in all patients. PMID- 1877163 TI - [Radiodiagnosis of malignant lymphoma of the small intestine]. AB - The authors observed 10 patients with malignant lymphoma revealed by x-ray; 2 of them were supposed to be afflicted with heavy alpha-chain disease with malignant transformation. An x-ray picture revealed a triad of pathognomonic symptoms and a regular parallelism of intestinal changes with clinicolaboratory findings. In all the cases the diagnosis was confirmed by morphological data. PMID- 1877164 TI - [Angiographic diagnosis of agenesia, aplasia and hypoplasia in children]. AB - Problems of the diagnosis of congenital renal developmental defects (CRDD) still continue to present a certain interest. Basing on their own experience in the diagnosis of CRDD in 188 of 527 children with renal pathology, the authors arrived at a conclusion that intravital diagnosis of renal aplasia was not only possible with the help of angiography, but also extremely necessary because agenesia and aplasia were two separate entities in their genesis, limiting the potentialities of reconstructive operations in aplasia. Hypoplasia in children was very frequent and was characterized by 5 types of the angiographic picture. Analyzing the state of the contralateral kidneys in CRDD, the authors considered some features of compensatory hypertrophy. PMID- 1877165 TI - [Dynamics of kidney function by renography findings in the connection to the results of radiotherapy of urinary bladder cancer]. AB - The paper is devoted to analysis of the potentialities of radionuclide renography as a method for assessment of the effectiveness of radiotherapy of bladder cancer. The results obtained suggested close correlation between change of renal function and the results of irradiation. Normal renal function was observed in 3 patients, improvement--in 16 patients, and deterioration--in 8 patients whereas a complete effect of radiotherapy brought about the following figures: 5, 11 and 3, respectively. A conclusion was made of a high significance of renography parameters in objective assessment of the results of radiotherapy of bladder cancer in conjunction with other therapeutic modalities. PMID- 1877166 TI - [Ultrasound and radiologic diagnosis of breast nodules in young women]. AB - Mammography as a priority method of diagnosis of breast nodules in young women is of low efficacy as a result of a dense background of the breast as distinct from echography permitting the detection of abnormal lesion against this background. Altogether 126 patients with clinical manifestations of breast nodules were investigated. Apparatus methods used for investigation of 38 of them, revealed but manifestations of fibrocystic mastopathy. Assessment of the efficacy of x-ray and ultrasound diagnostic methods was performed in 88 patients with breast nodules (the patients varied in age from 14 to 40). Radiodiagnostic accuracy in benign tumors was 54.1% that in malignant tumors--78.1%. Ultrasound investigation proved to be the most informative method for diagnosis of breast nodules in young women, and the use of a proposed algorithm would permit optimization of the diagnostic process. PMID- 1877167 TI - [Computerized tomography in the diagnosis of soft tissue neoplasms of the extremities and trunk]. AB - Analysis of CT data on 213 patients with soft tissue and trunk tumors has shown that a majority of malignant and benign tumors have a similar picture (except lipoma). Features of the contours of a tumor and its inner structure do not permit the assessment of its nature. The only significant differential-diagnostic sign of malignant soft tissue tumors is destruction of an adjacent bone, noted in 17.6%. The majority of malignant and benign soft tissue tumors (70.9%) on CT scans look like a single node; recurrent tumors look multinodular (78.2%). Verification of soft tissue tumors, revealed by CT, should be done using morphological methods. PMID- 1877168 TI - [Descending myelography with water contrast media by the methods of lateral puncture of the great occipital cisterna]. AB - A method of lateral puncture of the great occipital cistern for descending myelography with water soluble contrast substances was employed. It was used in 150 neurosurgical inpatients aged 4 to 70 with various diseases of the spinal marrow and its coats. A new water soluble drug iopamidol-200 (or 300) (Bracco, Italy) was used for diagnosis of spinal tumors. The drug dosage was worked out for adults as well as for children. A study was made of possible side-effects on a vast clinical material (80 patients). The new contrast substance iopamidol possesses better tolerance by patients and better roentgenocontrast properties than amipack. PMID- 1877169 TI - [Radiodiagnosis and radiotherapy of hemangiopericytoma (review of literature)]. PMID- 1877170 TI - [Radiodiagnosis of duodenal sarcoma]. PMID- 1877171 TI - [Cholangiography with selective catheterization of the bile ducts]. AB - The paper is concerned with the use of selective catheterization of the bile ducts during endoscopic cholangiocholecystography. This method alongside with routine ones was employed for investigation of 82 patients with pathology of the hepatoduodenopancreatic area, that helped to avoid diagnostic errors. PMID- 1877172 TI - [Echotomographic evaluation of normal hip joints in the newborn babies]. PMID- 1877174 TI - Update on Blue Cross & Blue Shield liquidation. PMID- 1877176 TI - Remarks at the 1990 WVU Investiture Ceremony. PMID- 1877175 TI - Things I know now that I didn't know or appreciate enough before serving in the legislature .... PMID- 1877177 TI - Parenteral and oral acyclovir for management of varicella pneumonia in pregnancy: a case report with review of literature. AB - Varicella pneumonia is a relatively rare disease in the reproductive-aged woman, but has a reported 41 percent maternal mortality rate in pregnancy. Seventeen cases managed with intraveneous acyclovir are reviewed. We report successful management with the unpublished addition of oral acyclovir to complete antiviral therapy on an outpatient basis. PMID- 1877178 TI - Adolescent perceptions of teenage morbidity and mortality in a rural population. AB - Health-related questionnaires were administered to 742 high school seniors in small towns in rural West Virginia. Students tended to overestimate the immediate threat to their health from cancer, heart disease and AIDS. They recognized a threat from auto accidents to their life and health in the immediate future, but nevertheless indulged in high-risk drinking and driving behavior. A surprisingly high percentage were concerned about stress and depression (40 percent) and suicide (11 percent). One-third of students had either planned or attempted suicide, suggesting that appropriate health education for this age group should include more emphasis on psychosocial issues and stress management. PMID- 1877179 TI - Medical students are saying "no" to practicing in West Virginia--what can be done about it? PMID- 1877180 TI - Diagnosis and antibiotic treatment of community-acquired pneumonia. AB - Only a few pathogens cause most community-acquired pneumonias. In outpatients, treatment is empiric, based on the results of chest films, leukocyte counts, and Gram's stains (if available). Antibiotics must always cover pneumococci and should cover Mycoplasma pneumoniae in young adults and during epidemic periods. A follow-up chest film in smokers and those older than 40 years is strongly recommended. In inpatients, the evaluation and treatment are tailored to individual cases. A search for a wider range of causes, using invasive tests if necessary, is undertaken, and all likely pathogens should be covered with the initial antibiotic therapy. PMID- 1877181 TI - Thrombotic thrombocytopenic purpura treated with plasma exchange or exchange transfusions. AB - Of 40 patients with thrombotic thrombocytopenic purpura, 17 were treated with plasma exchange, 15 with exchange transfusions, and 6 with both types of therapy. One patient died before being treated and another patient was seen but not treated. Plasma exchange was performed daily for a mean of seven exchanges per patient. The replacement fluid during plasma exchange was fresh frozen plasma in all cases. The complete response rates for each type of treatment were as follows: 88% for plasma exchange (15 patients), 47% for exchange transfusions (7 patients), and 67% for exchange transfusions and plasma exchange (4 patients). Clinical and laboratory factors were examined for any statistically significant association with therapy response. Treatment with plasma exchange was statistically the initial factor most strongly associated with prognosis. Paresis, paresthesias, seizures, mental status change, and coma showed no association with response to treatment. Some of the laboratory factors that did not show significant association with treatment response were the initial creatinine, hemoglobin, platelet count, lactate dehydrogenase, and total bilirubin. This study supports the hypothesis that plasma exchange has significantly improved the prognosis of patients with thrombotic thrombocytopenic purpura. These patients should be treated aggressively regardless of the severity of their symptoms. PMID- 1877182 TI - Access to medical care for documented and undocumented Latinos in a southern California county. AB - To determine local access to medical care among Latinos, we conducted telephone interviews with residents of Orange County, California. The survey replicated on a local level the national access surveys sponsored by the Robert Wood Johnson Foundation. We compared access among Latino citizens of the United States (including permanent legal residents), undocumented Latinos, and Anglos, and analyzed predictors of access. Among the sample of 958 respondents were 137 Latino citizens, 54 undocumented Latinos, and 680 Anglos. Compared with Anglos, Latino citizens and undocumented immigrants had less access to medical care by all measures used in the survey. Although undocumented Latinos were less likely than Latino citizens to have health insurance, by most other measures their access did not differ significantly. By multivariate analysis, health insurance status and not ethnicity was the most important predictor of access. Because access to medical care is limited for both Latino citizens and undocumented immigrants, policy proposals to improve access for Latinos should consider current barriers faced by these groups and local differences in access to medical care. PMID- 1877183 TI - Mentors and role models for women in academic medicine. AB - Senior mentors and role models have a positive influence on the career advancement of junior professionals in law, business, and medicine. In medicine an increasing number of women are pursuing academic careers, but available senior mentors to provide career guidance are often lacking. We report on the results of a national survey of 558 full-time faculty women, aged 50 years and younger, in departments of medicine in the United States, regarding their experience with role models and mentors. Women with mentors report more publications and more time spent on research activity than those without mentors. Women with a role model reported higher overall career satisfaction. This report, with illustrative examples, may be helpful to other women pursuing academic careers and to physicians who serve as mentors or role models to others. PMID- 1877184 TI - Hypoglycemias. AB - Low plasma glucose concentrations that may or may not be sufficiently low to result in symptoms can be observed as a concomitant of several diverse diseases. Treatment of the primary underlying disorder usually alleviates the hypoglycemia. For patients whose primary symptom is that of hypoglycemia, it is essential to confirm that the plasma glucose concentration is low during the occurrence of symptoms. Symptoms that occur after meals usually are mild and rarely signify serious disease. With rare exceptions, hypoglycemia resulting in major symptoms occurs in the food-deprived state. Lower concentrations of plasma insulin and C peptide and a concomitant low plasma glucose are major clues to a correct diagnosis. PMID- 1877185 TI - Penicillin allergy. PMID- 1877186 TI - Points to consider in the care of patients infected with the human immunodeficiency virus. PMID- 1877187 TI - Harmful health effects of passive smoking. PMID- 1877188 TI - Immunoglobulin G subclasses. PMID- 1877189 TI - Asthma without wheezing. PMID- 1877190 TI - Eosinophilia-myalgia syndrome. PMID- 1877191 TI - Chronic granulomatous disease. PMID- 1877192 TI - New uses of intravenous immune globulin therapy. PMID- 1877193 TI - Feline-transmitted sporotrichosis in the southwestern United States. PMID- 1877194 TI - Transmission of malaria in San Diego County, California. PMID- 1877195 TI - Daunorubicin, amsacrine, and sinus arrest. PMID- 1877196 TI - A time to lead, a time to follow. PMID- 1877197 TI - Women mentors needed in academic medicine. PMID- 1877198 TI - Hypoglycemia--a major risk of insulin therapy. PMID- 1877199 TI - An agenda for public health in the 1990s. PMID- 1877200 TI - AIDS awareness among rural Utah physicians. AB - Studies of physicians' attitudes and knowledge of the acquired immunodeficiency syndrome (AIDS) and the clinical precautions they take against exposure to the human immunodeficiency virus (HIV) have focused on urban physicians. To determine rural physicians' knowledge and attitudes about AIDS, a questionnaire was mailed to 321 physicians practicing in rural Utah. Of the 169 physicians who completed questionnaires, 96% thought that their community or area of service had only a minor or no problem with AIDS; 89%, however, thought that their chance of seeing a patient who was HIV-positive was fair to moderate. Of the 169 respondents, 3% were not sure whether they would even treat a patient who had AIDS, 67% said they would, and 30% said they would not. Although all physicians are at risk of seeing a patient who has had exposure to HIV and other blood-borne diseases such as hepatitis B, only 55% of the respondents felt a need to take clinical precautions to prevent their exposure to the virus. Our study shows the need for all rural Utah physicians to reevaluate their risk of exposure to HIV, to increase precautionary measures for their own protection, to consider the ethical responsibility of treating AIDS patients, and to take a more active role in teaching their patients how to protect themselves from exposure to the virus. PMID- 1877202 TI - Intranasal ethmoid sinus surgery, 1980 to 1990. AB - The Scientific Board of the California Medical Association presents the following inventory of items of progress in otolaryngology/head and neck surgery. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in otolaryngology/head and neck surgery that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Otolaryngology/Head and Neck Surgery of the California Medical Association, and the summaries were prepared under its direction. PMID- 1877203 TI - Treatment of vocal cord paralysis. PMID- 1877201 TI - Lyme disease. PMID- 1877204 TI - Phonatory diagnosis and phonosurgery. PMID- 1877205 TI - Skull base surgery. PMID- 1877206 TI - Functional endoscopic sinus surgery in children. PMID- 1877207 TI - Cochlear implants in children. PMID- 1877208 TI - Anticytoplasmic autoantibody test for Wegener's granulomatosis. PMID- 1877209 TI - Gadolinium magnetic resonance imaging in Bell's palsy. PMID- 1877210 TI - Laser therapy for early cancer of the vocal cords. PMID- 1877211 TI - Autoimmune or immune-mediated causes of deafness. PMID- 1877212 TI - Transoral approach to mandibular angle fractures. PMID- 1877213 TI - Alteration of the natural history of Pneumocystis carinii infection in patients with acquired immunodeficiency syndrome receiving aerosolized pentamidine. PMID- 1877214 TI - Tonic spasms in multiple sclerosis. Anatomic basis and treatment. PMID- 1877215 TI - Withdrawal effects of metoclopramide. PMID- 1877216 TI - Artificial urinary sphincter erosion in cardiovascular surgical patients. A cause for concern. PMID- 1877217 TI - Volunteering in West Africa. PMID- 1877218 TI - The fabric is sound but the edges are fraying. PMID- 1877219 TI - Hypocholesterolemia and malabsorption in HIV infection. PMID- 1877220 TI - The International Medical Corps. PMID- 1877221 TI - Preventing the contact dermatitis caused by a transdermal clonidine patch. PMID- 1877222 TI - Possible complications of acupuncture. PMID- 1877223 TI - Carbon monoxide poisoning. PMID- 1877224 TI - Reserpine as monotherapy for mild hypertension? PMID- 1877225 TI - What the doctor ordered. PMID- 1877226 TI - The health status of minority populations in the United States. AB - There is increasing national recognition that while our nation's health care system is the most expensive in the world, the health care status of Americans overall ranks poorly compared with other Western, industrialized nations. In the United States we tend to look at minority-majority variations of health status, as well as the variations of many other indicators by race or ethnicity, because race and ethnicity are particularly important components of our society. In general, health status indicators of minority Americans are worse than those of whites. In some locales, death rates of minority Americans are comparable to those of Third World nations. At the same time, minority Americans make up a rapidly increasing proportion of the nation's population and work force. Our baseline national data on some minority groups, however, currently are inadequate to detect shifts in health status. Finally, the rapidly expanding problem of the acquired immunodeficiency syndrome among some minority populations provides both an imperative and an opportunity to learn how model prevention programs should be designed and executed. PMID- 1877227 TI - Fine needle aspiration biopsy of superficial masses in children. AB - Fine needle aspiration biopsy (FNAB) is an underused diagnostic procedure in children, particularly in the evaluation of superficial masses. A total of 54 FNABs of superficial masses were performed in children aged 1 month to 15 years. Adequate material for diagnosis was obtained in 50 attempts. The cytologic diagnosis increased clinical understanding and provided a guide for treatment in 46 of the 50 cases. The cytologic diagnosis was confirmed in 15 of 19 patients who underwent an operation. Surgical intervention was obviated in 31 patients. There was one false-positive diagnosis of cancer. We describe the role of FNAB in children and its technique, accuracy, and diagnostic problems. PMID- 1877228 TI - Nonsteroidal anti-inflammatory drugs. Proposed guidelines for monitoring toxicity. AB - The most common toxicities of nonsteroidal anti-inflammatory drugs (NSAIDs) are gastropathy, renal dysfunction, and liver function abnormalities. We outline an approach to monitoring patients on long-term NSAID therapy, focusing on the early detection of complications. Gastropathy caused by NSAID use is more common in elderly patients or those with a history of dyspepsia, peptic ulcer disease, or alcohol abuse. Fecal occult blood testing and hemograms are less accurate in detecting gastropathy than direct visualization but are convenient and relatively inexpensive. We recommend the periodic use of these tests to detect NSAID-induced acute or chronic blood loss. Renal toxicity is seen in patients with preexisting renal disease or functional volume depletion and in the elderly. Complications include renal insufficiency, hyponatremia, hyperkalemia, and protein-uria. Renal function should be monitored during the first few weeks of NSAID therapy, especially in high-risk patients, with periodic testing thereafter. Hepatic toxicity is less common but warrants occasional determinations of alanine aminotransferase levels. Elderly patients and those with renal insufficiency or alcohol abuse have a higher risk of complications. Nonsteroidal anti-inflammatory drugs should be used cautiously in those patients at high risk for complications. Strategies can be used to limit toxicity. Patients taking these drugs long term should be monitored periodically for signs of blood loss, renal dysfunction, and hepatic dysfunction. PMID- 1877229 TI - Is deleting the digital rectal examination a good idea? AB - Many groups have taken the position that the digital rectal examination should be discontinued as part of the annual screening physical examination. We examined the effects of not doing a digital rectal examination on the early diagnosis of prostate cancer. The average time since a previous rectal examination increased as the stage of cancer increased. The digital rectal examination proved to be a relatively insensitive test, with 40% of stage D cancers being detected initially within 12 months of the most recent examination. Nevertheless, an annual digital rectal examination did detect a greater percentage of lower stage (and thus more localized and potentially curable) cancers when repeated within 12 months. When the last rectal examination was more than 24 months previous, cancers detected were more likely to be advanced. Without a digital rectal examination, patients would have their disease detected only by the presence of symptoms. When it was done because of symptoms, 81% of our patients had stage D cancers compared with 32% of stage B and 38% of stage C patients. Without the routine use of this examination, patients with prostate cancer would be more likely to have higher stage and less potentially curable lesions at the time of diagnosis. We conclude that the digital rectal examination remains an important part of routine annual physical examinations. PMID- 1877230 TI - The clinical diagnosis of splenomegaly. AB - Assessing for the presence of splenomegaly is an important component of the physical examination. Although several methods of palpation and percussion of the spleen have been described, until recently they have not been validated by noninvasive imaging techniques such as ultrasonography, radionuclide scanning, and computed tomography that offer objective means to assess splenomegaly. We review the literature comparing various physical examination techniques with noninvasive imaging modalities and conclude that palpation and percussion of the spleen are complementary but frequently insensitive and that further studies are needed to evaluate the efficacy of specific diagnostic methods. PMID- 1877232 TI - Painful subacute thyroiditis in Hawaii. AB - Between 1960 and 1982 we prospectively studied 269 patients with painful subacute thyroiditis to determine the demographic characteristics, seasonality, and natural course of the disease. The mean age for all patients was 37.1 years. The female:male ratio was 6.7:1. At the first visit, disease was bilateral in 69%. No epidemic or seasonal pattern was identified. The mean duration of thyroid tenderness was 2.2 months and that of palpable thyroid lumps was 2.8 months. This time difference, sometimes lasting many months, left a painfree "window" during which the palpable hard residual mass of subacute thyroiditis may be confused with other thyroid problems, especially cancer. PMID- 1877233 TI - Use of antiepileptic drugs in pregnancy. AB - The Scientific Board of the California Medical Association presents the following inventory of items of progress in neurology. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in neurology that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Neurology of California Medical Association, and the summaries were prepared under its direction. PMID- 1877231 TI - Understanding osteoporosis. AB - Considerable progress has been achieved recently in our understanding of the normal process by which bone mass is regulated. Age-related trabecular bone loss is characterized not simply by a global loss of bone but also by cortical porosity and loss of trabecular connections. Because bone strength depends on architectural as well as material properties, bone quantity alone cannot define fracture risk with precision. Traditional therapies for osteoporosis increase bone mass, and estrogen therapy, in particular, profoundly decreases fracture risk. The pharmacologic restoration of bone quantity and quality, however, remains elusive. Modern biotechnology offers the hope that progress may come about through the development of growth factors and other osteotropic compounds for clinical use. PMID- 1877234 TI - Human T-cell leukemia virus myelopathy. PMID- 1877235 TI - Acquired immunodeficiency syndrome dementia. PMID- 1877236 TI - Treatment of cluster headaches. PMID- 1877237 TI - Electroencephalographic brain mapping. PMID- 1877238 TI - Transcranial Doppler study. PMID- 1877239 TI - Myth of the chronic fatigue syndrome. PMID- 1877240 TI - Botulinum toxin therapy. PMID- 1877241 TI - Carotid endarterectomy. PMID- 1877242 TI - Intravascular (angiotropic) large-cell lymphoma ('malignant angioendotheliomatosis') with small vessel pulmonary vascular obstruction and hypercalcemia. PMID- 1877243 TI - Resolution of bowel obstruction due to newly diagnosed inoperable advanced ovarian cancer with medical therapy. PMID- 1877244 TI - Intractable hiccups as a presentation of central nervous system sarcoidosis. PMID- 1877245 TI - The trial and tribulation of Egerton Yorrick Davis. PMID- 1877246 TI - Subacute thyroiditis. PMID- 1877247 TI - Two medical worlds--separate and unequal. PMID- 1877248 TI - Cancer patients and support groups. PMID- 1877249 TI - Redwood Medicare Assignment Program. PMID- 1877250 TI - The sailor who couldn't play pool. PMID- 1877251 TI - Concerned patient. PMID- 1877252 TI - Identification of major allergens from the house dust mites, Dermatophagoides farinae and Dermatophagoides pteronyssinus, by electroblotting. AB - The allergens were separated from the extracts of house dust mites by SDS polyacrylamide gel electrophoresis (SDS-PAGE) and identified by autoradiography. Over 30 protein bands of the whole body extract of Dermatophagoides farinae were apparent on 10-20% gradient SDS-PAGE, and 13 bands with MW between 93KD and 12KD bound with specific IgE antibodies in patients' sera sensitive to house dust mites. The major allergenic component of the whole body extract of D. farinae was the protein of MW 14-15KD, which was detected in 95.7% of 47 patients' sera sensitive to house dust mites. The extract of Dermatophagoides pteronyssinus supplied by Bencard Company, England was thought to contain feces enriched material as noted in a few broad protein bands on SDS-PAGE. Seven allergenic components were shown by autoradiography. The protein band of MW 14-15KD was one of the most frequently revealed allergens on autoradiography, which has appeared in 32.5% of 40 patients' sera sensitive to house dust mites. The electrobotting technique used in the present study was fast, convenient and highly useful for both the identification of allergen components and the screening of specific IgE antibody. The individual variations of IgE immune responses to the allergenic components of the two house dust mites were discussed. PMID- 1877253 TI - Isometric and isokinetic torque curves at the knee joint. AB - Isometric and isokinetic torques of bilateral quadriceps and hamstrings were measured with Isokinetic Rehabilitation and Testing System (Model No. Cybex 340) on 40 normal untrained subjects, 20 males and 20 females, ranging between the ages of 23 and 35 years. The mean peak isometric and isokinetic torque values of both muscle groups showed no significant differences between dominant (right) and nondominant (left) limbs in both sexes; however there were significant differences between the male and the female. As the angular velocity increased, the peak torque significantly decreased, and the point of peak torque output occurred significantly later in the range of motion for quadriceps and hamstrings (p less than 0.01). There were no significant changes in the hamstrings to quadriceps (H/Q) ratios as the angular velocity increased. However, there were significant differences of mean H/Q ratio between male and female (p less than 0.01). Height had significant positive correlation with peak isometric and isokinetic torques for both quadriceps and hamstrings (p less than 0.01). Weight was found to correlate significantly with peak isometric and isokinetic torques (p less than 0.01). The mean isometric torques were significantly higher than the mean isokinetic torques for any joint angles in both sexes (p less than .01). PMID- 1877254 TI - Influence of nutrition on anti-tumor activity. AB - Nutritionally supporting the malnourished tumor bearing host may not benefit the disease outcome, but, rather, may preferentially "feed the cancer". We hypothesized that repletion is beneficial only when it augments an anti-tumor immune response. To support this hypothesis, 240 A/J mice were assigned to isocaloric dietary groups (24%, 5%, or 2.5% protein). On day 14 the mice received either immunogenic C1300- neuroblastoma (NB) or non-immunizing TBJ-NB. On day 21 half of the restricted animals were repleted with 24% protein chow. At day 35, chromium-release cell-mediated cytotoxicity was measured. In the group of mice that received 2.5% protein chow, nutritional repletion specifically augmented anti-tumor activity for C1300-NB which elicits a host immune response (33.78 L.U. (repleted) vs 3.47 L.U. (depleted) p less than 0.01), in contrast, nutritional repletion was detrimental for non-immunizing TBJ-NB, where further depression of cytotoxicity was seen (1.37 L.U. (repleted) vs 2.06 L.U. (depleted) 0 less than 0.01). This suggests that the influence of nutritional repletion in tumor nearing animals is dependent on the integrity of host's anti-tumor immunity. PMID- 1877255 TI - Neurosurgical application of fibrin adhesive. AB - We have tried fibrin adhesive, which mimics the end stage of plasmatic coagulation, in 26 patients with various neurosurgical problems such as: repair of cerebrospinal fluid (CSF) leaks, sealing of the vascular anastomosis sites, reinforcements of aneurysmal clippings, and hemostasis after resection of brain tumors. Presented in this report are 11 intracranial aneurysms, 11 brain tumors, 2 lipomyelo-meningoceles, and one each of cerebral arteriovenous malformation and torn dura resulting from a mastoidectomy. Procedures which seemed to be impossible or very difficult by conventional neurosurgical techniques could be accomplished in all cases without any complication. Our experience with fibrin adhesive suggests that it is a valuable adjuvant to various microneurosurgical procedures, and it may be potentially useful for protection of major cerebral veins and venous sinuses during cerebral retraction. PMID- 1877256 TI - Changes of cardiac output during treadmill exercise by impedance cardiography. AB - Nine athletes and ten nonathletes were selected randomly to study the changes of cardiac function during exercise by impedance cardiography. The speed of the treadmill was maintained at 3.4 mph, and its grade was increased by 1% (Balke protocol). The exercise was continued until the target heart rate (THR), 85% of maximum oxygen uptake (VO2max). The measured parameters for pre- and post exercise were stroke volume (SV), heart rate (HR), and cardiac output (CO). Average stroke volume of athletes at pre-exercise, 71.1 ml, was higher than that of nonathletes, 64.6 ml, and stroke volume of the former at post-exercise, 97.0 ml, was also higher than that of the latter, 85.2 ml. Therefore, despite the lower heart rate, cardiac outputs of athletes at pre- and post-exercise, 4.98 and 16.3 L/min, were higher than those of nonathletes, 4.87 and 14.2 L/min. For the second phase of the study, cardiac outputs of three subjects were measured during the continuous treadmill exercise with newly developed electrodes and shoes for minimizing motion artifact. Though there were several studies measuring cardiac output during continuous bicycle exercise, this is thought to be the first study in the world measuring cardiac output during continuous treadmill exercise without aid of ensemble averaging. PMID- 1877257 TI - Piriformis syndrome--a case report. AB - Piriformis syndrome, a term applied to an abnormal condition of the piriformis muscle, is characterized by symptoms and signs due to sciatic nerve entrapment at the greater sciatic notch. Recently we reviewed a case of unusual low back pain, radiating to the left lower extremity with tenderness particular in the left buttock. The patient was successfully treated by sectioning the piriformis tendon. We described the clinical features of a case of piriformis syndrome and reviewed the foreign literature. PMID- 1877258 TI - Two cases of nickel dermatitis showing vitiligo-like depigmentations. AB - The authors reviewed two patients showing "vitiligo-like depigmentations" where the skin had been in close contact with a metal spectacle frame made of nickel alloy. In spite of the hypersensitivity to nickel in both patients, they showed clinical and histologic findings indicate that the formation of "vitiligo-like depigmentation" does not result from posinflammatory hypopigmentation but from chemical hypomelanosis. We could not explain the underlying mechanisms; however, the speculation that the "vitiligo-like depigmentation" may come from the direct effect of the nickel itself, prompted us to report these cases. PMID- 1877259 TI - Giant malignant schwannoma of the diaphragm: CT and ultrasound findings. AB - A rare case of malignant schwannoma of the diaphragm is presented. The CT and ultrasound findings are described, correlated with the pathologic findings. During surgery, the tumor presented as a dumbbell shaped mass with central disruption of the right diaphragm. PMID- 1877260 TI - Congenital absence of pectoralis major: a case report and isokinetic analysis of shoulder motion. AB - Although pectoralis major plays an important role as a prime or assistant mover for the varied range of shoulder movement, there was no significant functional loss in ordinary activities in case of congenital absence of this muscle, because of compensation of surrounding muscles. This report describes a 22-year-old soldier with unilateral congenital absence of pectoralis major, who had difficulties in specific upper extremity movement, such as throwing or climbing. There was no visible or radiological evidence of associated anomalies of ipsilateral upper extremity. Electrodiagnostic study showed normal findings except delayed latency of medial pectoral nerve supplying rudimentary pectoralis minor of the involved side. On isokinetic study of movement for both shoulders, peak torque and average power for horizontal adduction were markedly-diminished on the involved side. PMID- 1877261 TI - An analysis of 2361 cases of renal biopsy in Korea. AB - To evaluate the distribution pattern of renal diseases based on needle biopsy, we analyzed 2361 cases of renal biopsy and necropsy material examined at the Department of Pathology from 1973 to 1988. The average age was 21.1 years for males and 23.7 years for females. The adult cases comprised 60.2% and the child cases 39.8%. The male to female ratio was 1.6: 1 in adults and 2.3:1 in children. Glomerular diseases were 97.8% of the total; primary glomerulonephritis (GN) 59.8% and secondary GN 27.6% The major glomerular diseases, in descending order of frequency, were; minimal change nephrotic syndrome (MCNS; 24.2%), IgA nephropathy (IgAN; 17.8%), benign recurrent hematuria (BRH; 8.8%), membranous GN (MGN; 7.9%), acute poststreptococcal GN (APSGN; 7.3%), mesangioproliferative GN (MspGN; 5.5%), minimal mesangiopathy (5.5%), membranoproliferative GN(4.1%), and focal segmental glomerulosclerosis (FSGS; 2.7%). GN of systemic disease included 77 cases of lupus nephritis, 157 cases of Henoch-Schonlein purpura nephritis (HSPN) and 7 cases of systemic infection excluding Hepatitis B viral hepatitis. The most common glomerular diseases were MCNS, IgAN, MGN and MspGN in adults, and MCNS, BRH, HSP-N and APSGN in children. HBs antigenemia was found in 71 cases, of which MGN and IgAN were the most frequent. HBs antigenemia-associated MGN was prevalent in male children, whereas IgAN was prevalent in adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877262 TI - Benign brainstem hemorrhage simulating transient ischemic attack. AB - A 48-year-old hypertensive man had sudden onset of symptoms suggesting vertebrobasilar insufficiency, which were transient in nature lasted for only 4 hours. Brain computed tomography revealed a small hematoma in the pontomedullary junction. This is an uncommon presentation of benign brainstem hemorrhage simulating transient ischemic attack. We propose that computed tomographic scan using thin slices of 3mm to 5mm thickness at the level of brainstem is required before starting anticoagulation therapy for vertebrobasilar transient ischemic attack. PMID- 1877263 TI - Combined use of ciprofloxacin and sucralfate. AB - The effect of sucralfate on the bioavailability of ciprofloxacin hydrochloride was assessed in 12 healthy male volunteers. The study was a four-period crossover design where subjects were randomized to one of four treatment sequences at entry. Treatments A, B, and C included sucralfate 2 g q12h for five doses. For treatment A, the fifth dose sucralfate was administered concurrently with ciprofloxacin 750 mg. For treatment B, 750 mg of ciprofloxacin was administered two hours before the fifth dose of sucralfate. Treatment C consisted of ciprofloxacin 750 mg six hours before the fifth dose of sucralfate. A 750-mg dose of ciprofloxacin was administered alone for treatment D. Blood and urine samples were collected at predetermined time intervals for 24 hours. Ciprofloxacin concentrations were determined by HPLC. The area under the concentration versus time curve from zero to infinity and the urinary recovery of ciprofloxacin were used for determining relative bioavailability. Concurrent administration of ciprofloxacin and sucralfate (treatment A) resulted in a significant decrease (p less than 0.05) in ciprofloxacin absorption. The relative bioavailabilities for treatments A, B, and C were 0.0429 +/- 0.0202, 0.829 + 0.21, and 0.965 + 0.32, respectively, relative to ciprofloxacin alone. In normal volunteers, ciprofloxacin may be administered between two and six hours before sucralfate, allowing sufficient time for ciprofloxacin absorption prior to the sucralfate dose and thereby minimizing the chance of a significant interaction. In patients with decreased gastric emptying the interaction may be more difficult to avoid. PMID- 1877264 TI - Comparative study of fluconazole and clotrimazole in the treatment of vulvovaginal candidiasis. AB - Fluconazole is a new oral triazole antifungal with good activity against Candida spp. In this study, we investigated the effectiveness and tolerability of a three day course of treatment with fluconazole compared with clotrimazole vaginal tablets in nonpregnant women with acute Candida vaginitis. Of the 90 evaluable patients who received fluconazole, 76 (84 percent) were asymptomatic seven to ten days after treatment compared with 84 of 95 (88 percent) treated with clotrimazole. An additional ten patients in the fluconazole group (11 percent) and seven in the clotrimazole group (7 percent) had improvement in their signs and symptoms. Only four patients in each group (4 percent) were considered treatment failures. Mycological cures were obtained in 89 and 93 percent of patients treated with fluconazole and clotrimazole, respectively, seven to ten days posttreatment. Clinical cure rates remained high one month posttreatment: 79 percent in the fluconazole group and 83 percent in the clotrimazole group. Both therapies were well tolerated. One patient discontinued treatment after she developed diarrhea while receiving fluconazole. The most common adverse effects associated with fluconazole use were nausea (six percent) and diarrhea (three percent). No clinically significant laboratory abnormalities were observed. In this investigation, oral fluconazole therapy was found to be as safe and effective as clotrimazole vaginal tablets in women with acute vulvovaginal candidiasis. PMID- 1877265 TI - Patient acceptance of Nordiject: a new drug delivery system for growth hormone. AB - Twenty-seven children, aged 5-20 years, with growth retardation were enrolled in an open study to evaluate the acceptability of a new injection pen (Nordiject 24, Novo Nordisk A/S) for administration of recombinant human growth hormone (r-hGH). Prior to this study, 17 of the patients had been receiving treatment with r-hGH administered via syringes and vials; their experiences with this conventional technique have been used for comparison with Nordiject. The injection pen is provided with a replaceable 27-gauge needle and a cartridge containing 24 IU of reconstituted r-hGH (12 IU/mL). A benzyl alcohol 0.9% solution is used as the solvent for the reconstitution. The pen can be regulated for doses from 0.5 to 8 IU per injection; regulation is accomplished by a turning movement. The patients had no problems with the dissolving procedure or handling the pen. Nearly two thirds of the patients experienced less injection pain with the pen as compared with the syringe. Special attention was paid to local tolerability, which was reported to be good. The thigh was the preferred injection site. The residual contents from 68 cartridges returned by the patients were analyzed for microbial contamination. Contamination was detected in only one cartridge, which could not be confirmed in a repeated test. Because of the simplification of the injection procedure afforded by the injection pen, 20 of 27 patients were able to perform the injections themselves and hence assume a more active role in their treatment. The patients who previously had been using conventional syringes strongly preferred the pen, and all patients wished to continue using the device. PMID- 1877266 TI - Aztreonam-induced myelosuppression during treatment of Pseudomonas aeruginosa pneumonia. AB - Aztreonam is a synthetic, monobactam antibiotic structurally related to the beta lactam class of drugs. It has inhibitory activity against many aerobic gram negative bacteria, although it does not inhibit gram-positive or anaerobic bacteria. Administration of aztreonam occasionally is associated with minimal and transient adverse effects. This case report describes a patient we believe experienced bone marrow suppression approximately ten days after aztreonam was given for treatment of pneumonia caused by Pseudomonas aeruginosa. This untoward effect primarily was manifested as neutropenia, although normochromic, normocytic anemia and thrombocytopenia were noted as well. One week after aztreonam was discontinued, the patient's bone marrow suppression resolved spontaneously. Although the mechanism responsible for myelosuppression is unclear, aztreonam may be implicated as the offending agent based on the temporal relationship between the development of neutropenia and its administration, and the resolution of neutropenia upon its discontinuation. PMID- 1877267 TI - Decreased hypoprothrombinemic response to warfarin secondary to the warfarin nafcillin interaction. AB - Patients who are receiving multiple medications must be screened for significant drug interactions. The specific mechanism of a drug interaction determines whether the patient may experience a subtherapeutic effect or a potentially toxic reaction. Three cases of relative warfarin resistance, possibly related to high dose nafcillin, are described in this report. Several reports have suggested that penicillinase-resistant penicillins, such as nafcillin and dicloxacillin, exert an important enzyme-inducing effect in patients receiving warfarin. This potential interaction must be appropriately recognized and managed in order to maintain adequate anticoagulation in this patient population. PMID- 1877268 TI - Flutamide-induced methemoglobinemia. AB - The authors report a case of clinical methemoglobinemia occurring one year after a patient began receiving flutamide 750 mg/d for prostate cancer with bone metastasis. The patient presented with severe cyanosis involving his lips and proximal extremities and moderate dyspnea. Methemoglobinemia was 16.2 percent of the total hemoglobin and intravenous ascorbic acid was administered. Clinical examination and laboratory analysis revealed no other cause. There was no biochemical evidence of congenital methemoglobinemia and no other regular drug use or chemical exposure was found. Moreover, clinical improvement and normalization of the methemoglobin level after the drug was discontinued is highly suggestive of flutamide-induced methemoglobinemia. Due to its chemical structure derived from anilide, flutamide may be considered as a potential methemoglobin-inducing agent. PMID- 1877269 TI - Chemical peritonitis associated with intraperitoneal vancomycin. AB - A case of chemical peritonitis associated with intraperitoneal vancomycin is reported. A 23-year-old woman presented with signs and symptoms consistent with a chronic ambulatory peritoneal dialysis catheter exit-site infection. Intraperitoneal vancomycin (Vancoled) 1 g was given, followed by 25 mg/L into each subsequent exchange. On day 4 the patient developed abdominal pain and cloudy dialysis effluent. The vancomycin was discontinued, and the dialysate cleared by day 8. Fluid cultures were negative, and Staphylococcus aureus was isolated from the exit site. Subsequent intravenous vancomycin, and smaller intraperitoneal doses, failed to repeat the event. Fluid and serum white blood cell count, serum immunoglobulins and complement, culture results, and the temporal relationship are strongly suggestive of a vancomycin-induced chemical peritonitis. PMID- 1877270 TI - Dextran inhibition of human immunodeficiency virus. PMID- 1877271 TI - Fluoxetine and suicidal ideation. PMID- 1877272 TI - The controversy of heparin therapy as an adjunct to thrombolysis in acute myocardial infarction. AB - Heparin is used routinely in the US as adjunct therapy for prevention of reocclusion after thrombolysis during acute myocardial infarction. A review of the literature shows controversy over the efficacy of heparin following thrombolysis. Both beneficial and a lack of beneficial effects have been reported with heparin. From a pathophysiologic viewpoint, there appears to be a need for full heparinization in the postlytic period because the residual stenosis is highly thrombogenic. However, optimal dose, time, and mode of heparin therapy has not been defined. Despite a lack of definitive data, it seems reasonable to administer intravenous heparin immediately after thrombolytic therapy to achieve a partial thromboplastin time 1.5-2.0 times control that is concurrent with an antiplatelet agent such as aspirin. These recommendations are consistent with the consensus opinion of the American College of Cardiology and the American Heart Association. PMID- 1877273 TI - Three-point versus two-point method for early individualization of aminoglycoside doses. AB - An approach using two serum concentrations following the initial dose of an aminoglycoside was retrospectively evaluated using the first and third samples from all three-point studies conducted by the pharmacokinetic consult service in 1988. The same Sawchuk and Zaske method was used for the three-point and two point studies. Although the predicted peaks and troughs from the two-point study were statistically different from those of the three-point study, it is the authors' opinion that the root mean squared error of 0.38 mg/L (95% confidence interval [CI] 0.31-0.45) for the peaks and 0.09 mg/L (95% CI 0.06-0.11) for troughs is well within the limits of acceptable clinical error for gentamicin and tobramycin. Eliminating one-third of initial aminoglycoside concentrations could result in significant time and cost savings. PMID- 1877274 TI - Optimizing drug delivery from metered-dose inhalers. AB - Metered-dose inhalers (MDIs) are being used with increasing frequency to administer medication used in the treatment of respiratory tract disorders. Inhaled medication is delivered directly to the tracheobronchial tree, allowing for a rapid and predictable onset of action. Studies show that only about ten percent of the dose from an MDI actually reaches the lung. The site of deposition within the lung is influenced by the aerosol characteristics, interpatient variability, and the technique by which the patient uses the inhaler. Spacer devices have been designed to overcome some of the problems encountered with MDIs and may be beneficial in certain groups of patients. The studies reviewed in this article suggest ways to alter the variables affecting inhalation in order to optimize drug delivery so that the patient will obtain the most benefit from the inhaled medication. PMID- 1877275 TI - Pharmacokinetic simulation of the effect of multiple-dose activated charcoal in phenytoin poisoning--report of two pediatric cases. AB - Activated charcoal is commonly used to inhibit the absorption of phenytoin after acute overdose. There are also reports of multiple-dose activated charcoal (MDAC) increasing the clearance of phenytoin in adults. We describe our experience modeling phenytoin pharmacokinetics during therapy with MDAC in the treatment of two cases of acute phenytoin poisoning in children. After extensive attempts at modeling the serum phenytoin concentrations, simulations were performed to identify the possible consequences of MDAC administration. Phenytoin elimination was more rapid than was expected, based on previously reported phenytoin pharmacokinetic parameters. Moreover, the time to peak phenytoin concentration and time course of phenytoin intoxication appeared to be shorter than available reports of phenytoin intoxication treated with a single dose of activated charcoal. MDAC may prevent continued phenytoin absorption and increase phenytoin elimination rate via gastrointestinal dialysis. The effect of MDAC on the clearance of phenytoin can be described by a first-order elimination rate constant of approximately 0.02-0.04/h. PMID- 1877276 TI - Tuberculosis in the elderly: incidence, manifestations, PPD skin tests, and preventive therapy. AB - Tuberculosis is a chronic infection caused by Mycobacterium tuberculosis. The incidence of tuberculosis has declined dramatically over the past decades, but it is still highly prevalent in the geriatric population. This report describes the etiology, clinical manifestations, and immunologic changes of tuberculosis in the elderly. The basis for tuberculin skin testing and its interpretation in patients over 65 years of age are discussed, as well as the controversies regarding preventive therapy with isoniazid in the elderly. Guidelines for tuberculosis screening in long-term care facilities are proposed. PMID- 1877277 TI - Adverse effects and drug interactions associated with fluoxetine therapy. AB - Fluoxetine, an inhibitor of serotonin reuptake, was released by the Food and Drug Administration in 1988 and was among the most prescribed drugs for that year. Although fluoxetine has been promoted as a safe antidepressant, a recent literature search revealed a number of case reports of adverse effects and drug interactions attributed to its use. This review familiarizes healthcare professionals with some of the currently known interactions and adverse effects and suggests ways of avoiding such events in clinical practice. PMID- 1877278 TI - Use of restricted antibiotics in primary care. AB - The objective of this study was to detect and evaluate the use of restricted antibiotics (RAs) in our ambulatory care site. We retrospectively analyzed 1084 treatments of a selected group of intramuscularly administered antibiotics that are usually considered restricted for use in hospitals. Five cephalosporins, four aminoglycosides, and one acylureidopenicillin were analyzed. The study was conducted in 47 primary health centers over six months. We reported the information on a special order form for parenteral prescriptions and evaluated the selection and the dosing interval of each antibiotic. Of the 1084 treatments, cefonicid was the antibiotic most frequently prescribed (61.3 percent), followed by tobramycin (15.3 percent), cefotaxime sodium (6.7 percent), amikacin (3.8 percent), cefuroxime (3.8 percent), mezlocillin (3.7 percent), netilmicin sulfate (3.7 percent), ceftizoxime sodium (0.8 percent), cefoxitin (0.5 percent), and streptomycin sulfate (0.4 percent). Based on our survey criteria, 59 percent of the 710 orders that indicated diagnosis had a correct or possibly correct indication; the remaining percentage was considered unnecessary therapy or poor drug choice. Of the 1050 orders that indicated a dosing interval, 75.4 percent showed an appropriate dosing interval. We assume that most of the infections treated in our ambulatory care site could be resolved with or without common antibiotics. In this study we obtained objective data of the use of ten RAs in order to determine if their use in ambulatory patients was justified. We observed that a small number of prescriptions agreed with the recommended criteria stated in this survey for use of these antibiotics in outpatient infections. PMID- 1877279 TI - Asthma, aerosols, and patient education. PMID- 1877280 TI - Research productivity and funding. PMID- 1877281 TI - Probable famotidine-induced thrombocytopenia. PMID- 1877283 TI - Comment: Pharm.D.: all or some? PMID- 1877282 TI - Gastric obstruction with extended-release tablets. PMID- 1877284 TI - Correction: clonidine patch toxicity. PMID- 1877285 TI - Primary acquired sideroblastic anemia and myelodysplastic syndrome from a geriatric point of view. AB - The median age of occurrence of primary acquired sideroblastic anemia is 74.4 years, with a range of 12 to 96 years (calculated from 452 cases). Of 445 cases, 60.4% were male, and 39.6% female. Not only primary acquired sideroblastic anemia, but the entire myelodysplastic syndrome must be considered as a disease of old age. PMID- 1877286 TI - [Biology of aging in Europe]. PMID- 1877287 TI - [Biology of aging in Europe]. PMID- 1877288 TI - The change in the supply with reduction equivalents in different organs of the rat during aging. AB - The rate of metabolic kinetics and the frequency of biological cycles may be correlated with the rate of aging and the maximum life-span potential. Therefore, investigation either into changes with age of such parameters within one species or into differences between species may give some information about the genetic programming of the aging process. Male Sprague-Dawley rats aged 3.5, 7, 12, 17, 23, and 33 months (m) were used to determine the changes with age of those metabolic pathways mentioned in the title, using the liver (LI), kidney (KI), brain (BR), heart (HE) and the skeletal muscle (SM). The maximum percentage of glucose utilization via the pentose pathway, compared to the total glucose utilization, was calculated after intravenous administration of D-[1-14C]- and D [6-14C]glucose by the determination of the trioses (as lipids) 3 hours after the application. Furthermore, in rats aged 13 and 25 m the kinetics of both glucoses was measured in liver, kidney, heart, brain, skeletal muscle, spleen (SP), and testes (TE) during the first 3 hours after application. Pentose pathway values were calculated. The results indicate a decrease in the glucose utilization via the pentose pathway in the course of aging in liver, kidney, heart and skeletal muscle and a decrease from 3.5 months on in brain, younger rats exhibit a higher rate of glucose utilization via the pentose pathway as do old ones, the reduction of the pentose pathway may possibly be the cause of higher lipofuscin accumulation in the cells of some organs, lacking sufficient reduction equivalents for lipid metabolism. PMID- 1877289 TI - Modifications of the biosynthesis of type-I and type-III collagens and fibronectin during diabetes and atherosclerosis. AB - Results show that diabetes, which is a major risk factor for arterio atherosclerosis, mimicks an accelerated aging, at least as far as the thickening of basement membranes and fibronectin and collagen biosynthesis are concerned. A similar sequence of events could be demonstrated in human atherosclerotic plaque formation. In conclusion, we could demonstrate a disregulation of extracellular matrix components biosynthesis (type-III collagen and fibronectin) in diabetes and atherosclerosis. PMID- 1877290 TI - Atherosclerosis starts in childhood--fact, myth or insinuation? AB - There is evidence that atherosclerotic vascular disease is observed already in childhood. The data on epidemiology, geographical variation and incidence is incomplete, and several risk factors have been identified and described. It is hoped that international collaborative research studies such as that on the effect of differences in nutrition or diabetes control in children, between our clinic and the Valle Hebron Children Hospital in Barcelona (sponsored by the Child Health Foundation) will generate knowledge on how to prevent premature atherosclerosis in childhood diabetes. PMID- 1877291 TI - Assessment of the age of atherosclerosis risk in population studies using a two factorial mathematical model. AB - The risk of atherosclerosis was assessed using a mathematical model of competition between LDL and HDL on 365 randomly selected persons. The results speak for the fact that the risk falls between the ages of 30 and 40 years for males, and 40 and 50 years for females. We are of the opinion that our procedure may be valid for sex comparison studies attempting to objectify the prevalence of atherosclerosis in population studies. PMID- 1877292 TI - Effect of smoking on different biological parameters in aging mice. AB - To investigate the harmful effect of smoking three groups of CBA/Ca male mice of different ages were subjected to smoking for different time durations. Body weight changes and acute cold tolerance were measured throughout the experiment. Thyroid hormone levels (T4, T3), TSH and lipid peroxidation products (as malondialdehyde and lipofuscin) were determined from either the blood or some organs. There was a decrease in body weight related to aging and it was most pronounced in the oldest animals (Group III). However, significant body-weight loss due to smoking was found in the youngest animals (Group I). Similarly, smoking resulted in a body-weight loss of the other two older groups (Groups II and III) as well. The greatest change in withstanding cold stress was measured in Group I and less so in Group II, as a consequence of smoking. Simultaneously, the youngest animals (Group I) showed the most remarkable changes in thyroxine (T4) and 3,3,4-triiodothyronine (T3) serum concentrations. Both hormone levels were significantly lower in the smokers. The T3 serum levels of the oldest animals (Group III) did not differ, while the T4 levels apparently increased. The TSH blood level in the oldest group was lower (by 20%) in the smokers compared to controls. Malondialdehyde (MDA) and lipofuscin content in most of the organs were considerably higher in the aging animals than those of the younger ones. The most significant elevations of these lipid peroxidation products were found in the smokers compared to the age-matched controls. The present results indicate that smoking probably accelerates the aging process. PMID- 1877293 TI - The influence of twelve weeks of aerobic training on the blood lipids of middle aged men. AB - Lipoprotein profiles revealed a significant increase in total cholesterol between trained and control groups and an increase of HDL-C in both groups after exercise. There were no significant differences in resting cholesterol levels, nor in LDL-C after exercise in both groups. The results of the study suggest that improvement in work capacity as a result of training is not necessarily accompanied by changes in the lipid profile. PMID- 1877294 TI - [Dementia and internal diseases: incidence of internal diseases in Alzheimer dementia, vascular dementia and other dementing diseases]. AB - The medical histories and postmortems of 30 patients with neuropathologically verified Alzheimer's disease were compared with a group of 20 patients suffering from vascular dementia and a group of 10 patients with other forms of dementia. The total numbers of clinically or pathologically diagnosed medical disorders did not show significant differences between the different forms of dementia. Metabolic, infectious, degenerative, and malignant disorders occurred with similar frequency in all investigated groups. Cardiovascular diseases were only slightly more common in patients with vascular dementia. In contrast to several earlier clinical or epidemiological studies, it has to be concluded that patients with Alzheimer's dementia cannot be considered physically "healthier" than patients with other forms of dementia. Therefore, they need the same medical attention as do other elderly demented patients. PMID- 1877296 TI - [Analysis of the self concept of independently living senior citizens]. AB - The analysis of research on self-concept of the elderly shows a need for more complex methods that measure not only self-esteem and subjective age identity, but also those that reflect the specificity of life in the elderly. The self concept of 140 elderly living in one community (65-93 years) was analyzed by an age-specific, self-concept interview. Factor-analysis resulted in a 10-factor assessment with the main factor being "bodily competency and purpose of life". Other factors were subjective age identity, composure, social integration, resignation, etc.. The subjects were cluster-analyzed. The first cluster contained almost 50% of the elderly who had a positive self-concept of competency, social integration, mood, and self-esteem; they were younger, often married, and in good health. Some clusters identified elderly with a moderate self-concept and some problems regarding health and activities of daily life. A very negative self-concept was shown by two groups of socially isolated (7.14%) and strongly physically and/or psychologically handicapped (5.71%) elderly, who had a generally negative self-concept and needed psychosocial therapy. Implications for further research are discussed. PMID- 1877297 TI - [From HSAN reports (Health and Nursing Care Liability Committee): 1,400 liability cases per year]. PMID- 1877295 TI - Changes of the glycosaminoglycan metabolism in human lung fibroblasts and porcine aortic endothelium cells influenced by the number of subcultures in vitro and by lipids in the medium. AB - In vitro aging fibroblasts and porcine aortic endothelium cells were treated with a commercial soy-bean lipid emulsion and incubated in 35S-sulfate or 3H glucosamine respectively. The glycosaminoglycans (GAGs) were characterized by enzyme digestion following proteolysis. Uronic acid concentrations were determined in fibroblast cultures. The GAG content is lower in the last possible passage than in the foregoing ones. Lipid treatment leads to an increase, especially in early passages. The incorporation of radiolabeled precursors decreases with increasing in vitro age in both cell types. By lipid treatment the heparansulfate (HS) radioactivity of fibroblasts is increased insignificantly, while the GAG radioactivity of endothelium cells and the chondroitinsulfate (CS) radioactivity of fibroblasts are decreased. The in vitro age-related reduction of the precursor incorporation is more pronounced in CS as compared to HS, whereby the HS radioactivity shows a percentual increase, especially following lipid treatment. The effect of lipids shows changes related to in vitro aging. The role of cellular GAG metabolism and lipid loads in arteriosclerosis is discussed. Even in the arterial wall different cell types may react differentially. PMID- 1877298 TI - [Researcher on future negotiations. The government should not interfere in it. Interview by Jan Thomasson]. PMID- 1877299 TI - [Life after heart surgery is easier with good information. Interview by Gunilla Lindberg]. PMID- 1877300 TI - [Kirsten Stallknecht, Danish Nursing Council: we are well-organized--this will give us power in the EEC. Interview by Christer Hansson]. PMID- 1877301 TI - [How shall we have it?]. PMID- 1877302 TI - [Quality work gives appetite in Halmstad. Interview by Carina Roxstrom]. PMID- 1877303 TI - [Nurse led relief action to Romania. Interview by Jan Thomasson]. PMID- 1877304 TI - [Lidkoping, a safe and secure community. Interview by Stefan Samuelsson]. PMID- 1877305 TI - [Fredrika Bremer (1801-1865)]. PMID- 1877306 TI - [Eva's research is down to earth and useful. Interview by Elisabet Forslind]. PMID- 1877307 TI - [Bohus district introduces new measuring method for cost and quality]. PMID- 1877308 TI - [Good working environment--a question of body and soul. Interview by Jan Thomasson]. PMID- 1877309 TI - [SHSTF protest in Dalarna--physicians' wage increase an affront against all others. Interview by Jan Thomasson]. PMID- 1877310 TI - [Histo-Center--the laboratory is always open. Interview by Elisabet Forslind]. PMID- 1877311 TI - [Research activities are on track]. PMID- 1877312 TI - [Hildegard is school children's health enterprise. Interview by Carina Roxstrom]. PMID- 1877313 TI - [Dea Trier Morch, 1941-]. PMID- 1877314 TI - [Psoriasis--the great hidden widespread disease]. PMID- 1877315 TI - [Malignant melanoma--nurses can make a contribution in preventive activities]. PMID- 1877316 TI - [Condyloma--laser treatment gives positive results]. PMID- 1877317 TI - [Neonatal care--when you were small]. PMID- 1877318 TI - [A revolutionary in maternal care. Interview by Elisabet Forslind]. PMID- 1877319 TI - [To be a midwife is a natural choice for me]. PMID- 1877320 TI - [Say helloh to the public]. PMID- 1877321 TI - [Need written orders!]. PMID- 1877322 TI - [In neonatal medicine there is a risk of giving too big a dose. Interview by Elisabet Forslind]. PMID- 1877323 TI - [Reduced interest in agreement with profession]. PMID- 1877324 TI - [Investing in education]. PMID- 1877325 TI - [Red pencil affects education reform. Swedish nurses are no good in the EEC in continuing education either]. PMID- 1877326 TI - [Care for the aged according to the Danish model: in Strand patients are boarding guests with a personal life]. PMID- 1877327 TI - [Svava Jakobsdottir (1930-)]. PMID- 1877328 TI - [Administration of prostaglandin E1 in diabetics and non-diabetic patients with severe Fontaine stage IIb arterial occlusive disease]. AB - The success in therapy of prostaglandin E1 intra-arterially and intravenously applied to diabetics and non-diabetics with PAOD, stages IIb-IV according to Fontaine, was scrutinized in a city hospital primarily concerned with geriatrics, metabolism, and angiology. All the patients included were examined in retrospective studies with regard to the improvement of their situations during their stays in hospital and--in addition to that--a part of them prospectively some time after their stays in hospital. In all, 99 patients were included in the retrospective examination of which there were 60 diabetics and 39 non-diabetics. Of the 60 diabetics 53 were in stage IV, 5 in stage III, and 2 in stage IIb while in case of non-diabetics 26 were in stage IV, 10 in stage III, and 3 in stage IIb. 50 of the diabetics and 27 of the non-diabetics were treated intra arterially. The prospectively orientated post-observation included 38 diabetics and 24 non-diabetics. The results of the retrospective examination revealed a significantly superior efficiency of intra-arterially applied PGE1 compared with the intravenous application, both, with regard to the reduction of needed analgesics and the improvement of the clinical situation. A comparison between intra-arterially treated diabetics and non-diabetics showed a significantly higher rate of success of the diabetics regarding to the improvement of the clinical situation. Concerning the prospective post-examination: due to their PAOD the diabetics took significantly more often analgesics at the time of their post-examination than the non-diabetics. Also concerning the development of their clinical situations the diabetics turned out to have worse results than the non diabetics, however, the differences were not significant in this case. PMID- 1877329 TI - [Effect of stepwise hypervolemic versus isovolemic hemodilution in patients with intermittent claudication on muscle oxygen pressure during exercise]. AB - In patients with intermittent claudication and concomitant high hematocrit values a stepwise hypervolemic hemodilution versus isovolemic hemodilution (intravenous infusion of 500ml 10% hydroxyethylstarch solution (HES)(mean molecular weight 200.000/substitution degree 50%) or vensection and subsequent infusion of 10% HES (200/0.5)) were performed intraindividually. Measurements of muscle tissue oxygen pressure (pO2) values using a standardized pedalergometric exercise test as well as the pain free walking distance using a standardized treadmill were performed. Optimal results of muscle tissue oxygen pressure (pO2) behaviour after pedalergometric exercise test as well as muscular performance on the treadmill were found using isovolemic hemodilution at an average hematocrit value of 40.60%. In contrast, hypervolemic hemodilution at a comparable hematocrit level (40.50%) induced a "retarded reactive hyperoxia" and only a moderate increase of painfree walking distance. PMID- 1877330 TI - [Incidence and symptomatology of lung embolism in relation to the site of deep venous thrombosis]. AB - The uncertainty about the true incidence of pulmonary embolism (PE) in connection with deep venous thrombosis (DVT) becomes evident when comparing the results of autopsy--vs. clinical studies, with the former showing a three-fold elevated rate of embolisation. In order to evaluate the percentage of clinically inapparent PE, all patients (65 females, 54 males, mean age 61.3 years) hospitalized between April 1989 and March 1990 with suspected DVT and/or PE underwent duplex sonography and pulmonary scintigraphy. In 108 cases, DVT could be ascertained, whereas 11 patients only suffered from PE. In 57.4% of all DVT, PE was diagnosed. Of the 73 cases with PE, only 53.4% of the patient stated typical symptoms primarily. In more than 1/4 of the patients with primary symptoms of PE, no DVT could be diagnosed. There was no significant difference between the occurrence of PE in relation to the localisation of DVT, with 1/3 to 1/2 being asymptomatic. 1/4 of the patients with leg-thrombosis and 1/7 with thrombosis of the iliac vein did not complain of typical symptoms of thrombosis. Furthermore, an increased PE rate seems to occur with an elevated ultrasound echogenity of the thrombus. As a result of the study pulmonary szintigrams seem to be indicated in all cases of DVT in order to evaluate the total PE risk. PMID- 1877331 TI - Visceral ischemia following aortic surgery. AB - Intestinal ischemia after aortic surgery is a rare (1-5%) complication, often with a fatal outcome (greater than 50%). During the period 1974-1987, 554 abdominal aortic operations were performed in our department. 17 patients (3%) were reoperated due to bowel ischemia, ten of these patients died. 12 patients were operated on due to aortic aneurysm (9 emergency operations) and 5 due to occlusive disease. A retrospective analysis of the files of the 17 patients was performed to try to identify the risk patient. Preoperative investigations demonstrated that the inferior mesenteric artery (IMA) was patent in 3 patients and occluded in 5 patients. As to the other 9 patients no information could be found (all with aneurysm). After the primary operation, 11 patients had persistent circulation via at least one of the hypogastric arteries and none of them had persistent circulation via the IMA. 11 patients had bloody diarrhea before reoperation and in 6 patients peritonitis was observed. Rectoscopy was performed in 8 patients and in 7 there was indication of ischemia. The most common finding among the laboratory tests was a rise in the creatinine level which was observed in 10 patients. Other laboratory tests such as blood gases, leucocytes, thrombocytes or temperature were of little predictive value per se. Patients operated on due to ruptured aortic aneurysm are risk patients. No other predictive symptom or sign was found to preoperatively identify the patient at risk for intestinal ischemia. An intraoperative method for evaluating the intestinal blood flow would be of great value when considering selective intestinal vascular reconstruction. PMID- 1877332 TI - [Mid-term results of our first 53 "in situ" bypasses]. AB - The "in situ" bypass technique was adopted by our group in 1986. A total of 53 "in situ" bypasses were carried out until June 1989. The worst symptoms were incapacitating claudication, rest pain or ischemic necrosis, each in about one third of the patients. The site of the distal anastomosis was the popliteal artery below the knee in 40 instances, the peroneal artery in 7 and other infrapopliteal vessels in 6. Valve incisions were performed uneventfully with re usable instruments featuring a sharp-edged blade and an indicator for rotation control of the blade ("Insitutom RG"). Vein branches were located mostly by angiography, but residual arterio-venous fistula remained a vexing problem. In the beginning they were ligated under local anaesthesia. Later on they were dealt with successfully using transluminal embolization. Patients were last examined in July 1990 when the follow-up time ranged from 12 to 51 months. 5 patients had died and 5 were lost to follow-up. Patency rates were evaluated according to the life-table method. They were gratifying for femoro-popliteal bypasses with 87% after one year and 83% after two and three years. Femoro-tibial-peroneal bypasses performed below average, but their number was too small to draw conclusions. PMID- 1877333 TI - [Infra-inguinal arterial reconstruction: in situ or reversed venous bypass?]. AB - Since 1984 one of our surgeons treated 154 patients for infrainguinal arterial insufficiency. The patients had a mean age of 72 years and suffered from multiple concomitant diseases. The indication for operation consisted in a chronic critical ischemia in every case. 98 reversed (RV) and 56 in situ (IS) vein bypasses had to be implanted. No statistical significant differences could be found concerning survival, graft patency and limb salvage (life table analysis). Nearly half of our patients died during the 5 year observation period. The cumulative 5 year graft patency and limb salvage rate was 86% and 89% in the RV and 80% and 84% in the in situ group. PMID- 1877334 TI - [Peri-capillary fibrin cuffs--an O2 diffusion block?]. AB - In 42 patients with a chronic venous insufficiency Stage I-III transcutaneous oxygen tension was measured above the medial ankle and the leg ulcer edges respectively at 44 degrees C. The measurement point was biopsied and evaluated immunfluorescencehistologically for pericapillary fibrin cuffs (PCF). Fibrin cuffs are associated with decreased tcpO2-tensions. All PCF-positive biopsies were from areas with a tcpO2 less than 35 mmHg. The difference of PCF-positive and PCF-negative biopsies concerning the mean tcpO2 was significant (Wilcoxon-U Test; p less than 0.001). The evidence of pericapillary fibrin cuffs associated with tcpO2 tensions up to 33 mmHg proves that this phenomenon alone cannot be a diffusion barrier. PMID- 1877335 TI - A single blind randomized, controlled trial of hydrotherapy for varicose veins. AB - Sixty-one patients suffering from primary varicosity were divided into 2 groups, one receiving regular hydrotherapy, the other no such treatment for 31/2 weeks. Objective evaluation of the venous competence showed an apparently greater benefit in the control group in respect to light reflex rheographic venous filling time. The leg volume changes, however, indicated a stronger and more persistent reduction in the experimental group. The same applied for ankle and calf circumferences, which were reduced significantly only in patients treated with hydrotherapy. Furthermore some (but not all) of the subjective symptoms yielded significantly more frequent improvement in this group. In conclusion this controlled study implies that hydrotherapy may help patients suffering from primary varicose veins, a notion which was previously often stated but so far not scientifically verified. PMID- 1877336 TI - Recurrent bleeding from a hepatic artery aneurysm feeding a large cavernous hemangioma of the liver. AB - We describe a patient with an aneurysmatic dilatation of the hepatic artery feeding a giant cavernous hemangioma. The 51-years-old man presented with massive gastrointestinal hemorrhage due to chronic rupture of the aneurysm into the pancreatic duct. The patient died 25 days after resection of the aneurysm in liver failure and septic shock. We think that this cavernous hemangioma was responsible for a high blood flow within the hepatic artery for many years. This high blood flow caused the degenerative alterations in the wall of the artery, resulting in aneurysm formation and rupture. This is the first case mentioned in literature with rupture of a hepatic aneurysm generated by high blood flow. PMID- 1877337 TI - [Arteriovenous fistula of the superior mesenteric artery after resection of the ileum]. AB - Acquired arterio-venous fistulas of the superior mesenteric artery are a rare event following abdominal injuries or surgery. Clinical symptoms present as cramplike abdominal pain and diarrhea with a history of previous laparatomy or a penetrating abdominal trauma. The clinical examination may reveal a paraumbilical pulsation with flow murmur. The exact localization and the extent of the a.-v. fistula may be established by selective arterial mesentericography. An urgent vascular reconstruction is indicated in order to prevent secondary alterations due to portal hypertension. Apart from vascular surgery, successful percutaneous catheter embolization has been reported. PMID- 1877338 TI - [Secondary aorto-duodenal fistulas as a cause of massive gastrointestinal hemorrhages]. AB - Aorto-duodenal fistulas represent a rare but highly dangerous complication following reconstructive aortic interventions. They may be the source of severe gastrointestinal hemorrhages. The recognition of cause and localization of the latter may be difficult. Only an immediate diagnosis permits urgent surgical intervention and may prevent the otherwise fatal outcome. The importance of an early diagnosis is underlined by two case reports. PMID- 1877339 TI - Upper extremity aneurysms. AB - Five cases of upper extremity aneurysms are reported in 4 male and 1 female patients. Four were of traumatic and one of arteriosclerotic origin. Diagnosis and treatment are discussed. PMID- 1877340 TI - [Vascular lesions in Behcet's disease]. AB - Vascular lesions in Behcet's disease are generally localized in the venous system: up to 24% of the cases reported in the literature are accompanied by thrombosis/thrombophlebitis. Reports of arterial involvement are rare but have increased during the last decade. Surgical treatments of arterial aneurysms and occlusions are often followed by recurrences due to progression or relapses of the inflammatory vessel wall lesions. Aneurysms of the pulmonary artery are rare. They may be complicated by thrombosis within the aneurysm and massive hemoptysis due to bronchial erosion and formation of an arterio-bronchial fistula. 27 cases of Behcet's disease are reported. PMID- 1877342 TI - [A histo-anatomical study on the spleens of a frilled shark, Chlamydoselachus anguineus]. AB - The spleens of a frilled shark, Chlamydoselachus anguineus was histo-anatomically studied. The results were as follows. 1. Two independent spleens, one in the dorsal mesogastrium and the other in the ventral mesenterium (Ligamentum hepatoduodenale), are noted. Splenic branches are provided either from a. lienogastrica for the former or from Truncus coelomesentericus for the latter. The venous system holds a non-collateral position to the arterial system and drains the intrasplenic blood by complicate routes. The vascular architecture of the intestinal tract of Chlamydoselachus is same as that of the sixgill shark, Hexanchus. 2. Histologically, both spleens consist of the white pulp (arteries and periarterial lymphatic sheath) and the red pulp. No active hemopoiesis is noted. Ellipsoids are present around arterial terminals. Arterial terminals communicate directly to venous vessels of the red pulp. Both incompletely-formed collateral veins of intrasplenic arteries and capsular drainage veins are noted. These features are essentially same as those of other elasmobranch spleens. PMID- 1877341 TI - [Hypothenar hammer syndrome]. AB - The relatively rare Hypothenar Hammer Syndrome is presented and discussed, illustrated by two cases. Percutaneous blockage of the stellate ganglion is suggested in order to prevent the amputation of the affected finger or fingers. PMID- 1877343 TI - [A case of the persistent sciatic artery]. AB - During the dissecting practice of students at Gifu University School of Medicine in 1989, a rare developmental anomaly showing the sciatic artery was found in the left lower limb of a cadaver of 88-year-old Japanese female. The left sciatic artery (5 mm in diameter) arose from the internal iliac artery and appeared at the buttock between the piriformis and superior gemellus muscles through foramen infrapiriforme. The femoral artery (6 mm in diameter) of the left lower limb was normal in distribution and belonged to the type III by Adachi's classification (1928). The terminal vessel of the femoral artery was joined to the sciatic artery at the popliteal fossa. PMID- 1877345 TI - Topographical anatomy for sinus surgery. PMID- 1877344 TI - [The relationship between the sympathetic nerves and immunocytes in the spleen]. AB - Ever since Galen, the ancient Greek physician, said "Melancholic women develop disease more than sanguine women," it has been said that the mental condition affects the physical condition. However, there is hardly any scientific verification. About half a century ago, Selye (1936) proposed a relationship between stress and immune function, and it is becoming increasingly clear that the nervous system and immune system interact with each other. Also researchers have strongly hoped to demonstrate the existence of specific pathways by which immunocytes can be directly regulated by the nervous elements instead of by the humoral influence of immunomodulators. In this study, the author showed by electron microscopic observation how the immunocytes in the guinea pig spleen are directly innervated. The sustentacular supporting element of the guinea pig spleen is the connective tissue system which includes the capsulo-trabecular, peri-vascular and reticular systems. The latter system is composed of the outer sheath of the reticular cell or its cellular processes which have abundant microfilaments and the inner minute connective tissue space in which lamina densa like material, collagenous fibrils, elastic fibers and nervous elements are present. The sympathetic adrenergic nerves for the spleen enter the organ, and scatter around the arterial walls. All components of the connective tissue system are continuous with each other, and the nervous elements appearing in the reticular system are the elongated ones from other connective tissue systems, especially peri-vascular connective tissue. Thus, the adrenergic nerves are more abundant in the white pulp, into which the central artery penetrates, than in the red pulp which arterioles or capillaries pass through. The minute connective tissue space of the reticular system may be called the noradrenalin (NA) canal because catecholamine released from the naked adrenergic nerve terminals in this tissue diffuses and is stored in this enclosed space. The reticular system in the spleen divides the parenchyma into small non-endothelial vascular spaces owing to its meshwork, and free mobile immunocytes, such as T-cells, B-cells and macrophages, stagnate in these spaces. This stagnation of the mobile immunocytes and the presence of the adrenergic nerves in the NA canals provide the chance for the immunocytes and nerves to meet each other in the following fashion; the reticular cell sheaths show the exposed phenomena owing to the contraction of the microfilament-rich reticular cell processes, caused by noradrenalin in the NA canal, and the nervous elements in the NA canals can face the nonendothelial vascular spaces where mobile immunocytes pass freely.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1877346 TI - Hyperresponsiveness to tussive stimuli in cigarette smoke-exposed guinea-pigs: a role for capsaicin-sensitive, calcitonin gene-related peptide-containing nerves. AB - Environmental pollutants may induce airway hyperresponsiveness to bronchonconstrictor stimuli, but if there is a concomitant change in other defensive reflexes, like the cough reflex, is not known. We have examined how two weeks' exposure to cigarette smoke influences airway sensitivity to inhaled irritants acting mainly through capsaicin-sensitive sensory neurons (citric acid, capsaicin) or rapidly adapting stretch receptors (cigarette smoke, histamine). Guinea-pigs were exposed, over a period of one hour, to cigarette smoke or room air, twice daily for 2 weeks. Twenty-four hours after the end of the smoke exposure coughing produced by nebulized citric acid (0.40 M) and capsaicin (30 microM) was enhanced 3.7 (P less than 0.001) and 2.5 (P less than 0.05) times, respectively, whereas the cigarette smoke-induced cough was unchanged. The enhanced responsiveness gradually returned to normal over a period of three weeks and was not mediated by cyclo-oxygenase products since it was not affected by indomethacin (3 mumols kg-1). In contrast, the broncho-constrictor responses to citric acid, capsaicin, cigarette smoke and histamine (0.70 mM) were not altered by inhalation of cigarette smoke. Smoke-exposed animals had a significantly (P less than 0.05) increased amount of calcitonin gene-related peptide-like material (CGRP, contained in capsaicin-sensitive sensory neurons) in tracheal tissue, suggesting that chronic irritation stimulates peptide synthesis. The amount of neuropeptide Y-like material (in autonomic motor nerves) in pulmonary tissue was not changed indicating some 'specificity' in the irritative effect of smoke. It is concluded that prolonged exposure to cigarette smoke produces a tussive hyperresponsiveness that seems to involve specifically capsaicin-sensitive, CGRP containing sensory neurons mediating cough. The present data demonstrate the development of a 'sensory' hyperresponsiveness, separate from airway hyperresponsiveness to bronchoconstrictor agents. PMID- 1877347 TI - Dual effects of vasoactive intestinal peptide (VIP) on leucocyte migration. AB - Vasoactive intestinal peptide, at different concentrations, was tested on the migration of leucocytes by using the sealed capillary migration test. Vasoactive intestinal peptide, at 10(-7)-10(-9)M, inhibited, while at 10(-12)-10(-14)M, stimulated mononuclear leucocyte migration. The migration of polymorphonuclear leucocytes was inhibited by vasoactive intestinal peptide at 10(-6)-10(-9)M, a stimulation was found at 10(-13)-10(-14)M. The inhibiting effect of vasoactive intestinal peptide on leucocyte migration was abolished when vasoactive intestinal peptide was split into C- and N-terminal fragments, while a stimulating effect was retained in the N-terminal fragment, at 10(-14)M, for mononuclear cells. Helodermin and peptide T, as well as two other members of the secretin-glucagon family, secretin and gastric inhibitory peptide, had no effect on the migration. When VIP antiserum was tested, it had an inhibiting effect, which was not seen with control serum, supporting a physiological effect of the lower vasoactive intestinal peptide concentrations. Vasoactive intestinal peptide seems to have dual effects on mononuclear and polymorphonuclear leucocyte migration and, generally, intact vasoactive intestinal peptide seems to be needed for these effects. PMID- 1877348 TI - The contribution of ultrafiltration pressure for glomerular hyperfiltration in young nephrectomized rats. AB - Ablation of renal tissue in infancy is followed by increased ultrafiltration pressure, enlarged filtering area and decreased hydraulic conductivity of the glomerular capillaries. This study examines the effect of a calcium channel blocker, felodipine, on ultrafiltration pressure and renal function in rats uni nephrectomized at 5 days of age. The rats were treated with felodipine from 24 to 60 days of age or left untreated. Sham-operated untreated rats were used as controls. Arterial blood pressure levels were similar in the three groups of rats. Glomerular filtration rate and renal plasma flow in the left kidney were significantly higher in treated and untreated rats than in sham-operated untreated rats; significantly higher values were also found in treated than in untreated rats. Single nephron glomerular filtration rate was significantly higher in treated and in untreated than in sham-operated untreated rats, but was not different in treated and untreated rats. Ultrafiltration pressure was significantly higher in untreated rats than in treated and in sham-operated untreated rats. Ultrafiltration coefficient (Kf) was significantly higher in treated rats than in untreated and sham-operated untreated rats. Hydrolic conductivity of the glomerular capillaries was significantly lower in untreated than in treated and in sham-operated rats, but was not different in treated and sham-operated rats. Glomerular volume was higher in treated and untreated rats than in sham-operated rats. CONCLUSION: high ultrafiltration pressure is not an absolute requirement for the hyperfiltration that follows infant nephrectomy. PMID- 1877349 TI - Oedema-preventing mechanisms in a low-compliant tissue: studies on the rat tail. AB - The long-term effect of elevated tail venous pressure (Pv) on interstitial fluid pressure (Pi) and colloid osmotic pressure (COPi) was studied in rats. Measurements were performed on different rats after 1-5 days of congestion, and on a sham operated control group. Two different degrees of venous stasis were obtained by means of graded ligation of tail veins and skin. Moderate degree of ligation (group 1) caused no visual oedema. More extensive ligation (group 2) gave marked oedema already on day 1 and further progression and exudation from the skin during the following 3 days. Tail venous pressure was measured by micropuncture and interstitial fluid pressure by the wick-in-needle technique. Interstitial fluid was sampled by a dry wick method, and colloid osmotic pressure was measured with a membrane osmometer. In group 1, Pv had increased from 6.5 to 21.5 mmHg on day 1, and thereafter remained unchanged. Interstitial fluid pressure increased from 3.4 to 16.9 mmHg after ligation and to 19.2 mmHg on day 1. Colloid osmotic pressure fell from 11.7 to 5.8 mmHg. From day 1, both interstitial fluid pressure and colloid osmotic pressure remained largely unchanged. In group 2 rats, tail venous pressure increased to 33.0 and 36.3 mmHg on day 1 and 2 and then fell towards control level during the following 3 days. Interstitial fluid pressure increased to 22.9 and 31.4 mmHg before a rapid decline towards control level. Colloid osmotic pressure was reduced from 11.7 to 5.6 mmHg. We conclude that hydrostatic counterpressure may provide an oedema preventing effect of up to about 15 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877350 TI - Transmural fibre direction in the anterior wall of the feline left ventricle: theoretical considerations with regard to uniformity of contraction. AB - Previous studies of non-uniform performance of a myocardial region have indicated that measurement of local contraction is vectorial. Myocardial performance in one direction mainly, but not exclusively, depends on performance of the wall fibres in this same direction irrespective of wall depth. In this study we therefore determined fibre direction across the anterior wall of the left ventricle in twelve cats. Based on the fibre configuration a simple model is developed to analyse and predict the degree of uniformity of contraction. Fibre direction shifted continuously across the wall, from almost alignment with global apex-to base axis in the endocardium (90 degrees), to close to the equatorial direction (0 degrees) in the midwall, and finally to about -50 degrees in the epicardial layer. The model predicts less uniformity with reduction of preload, and in the event of subendocardial ischaemia, which fits well with experimental data. Analysis of uniformity based on the integrated vectorial contribution of all myocardial layers thus provides a way to quantify regional uniformity/non uniformity as a regulatory mechanism of cardiac function. PMID- 1877351 TI - Is the humoral renal antihypertensive activity of the spontaneously hypertensive rat (SHR) reset to the high blood pressure? AB - The kidneys have a humoral antihypertensive system, located in the renal medulla and presumably antagonizing the pro-hypertensive renin-angiotensin system. Medullipin I and II and maybe platelet activating factor (PAF), seem to be the mediators of this system, known to be activated after reversal of renovascular hypertension or when the perfusion pressure to a normotensive kidney is suddenly elevated. The present study was undertaken to investigate whether this system is functioning also in the spontaneously hypertensive rat (SHR), and if it is then reset in proportion to the increased mean arterial pressure (MAP). Isolated kidneys from spontaneously hypertensive rats and from Wistar Kyoto rats (WKY) were cross-perfused in vivo from anaesthetized intact Wistar Kyoto rat 'donors'. After 30 min of perfusion at 100 mmHg the perfusion pressure to the isolated kidneys were, for 60 min, either kept unaltered at 100 mmHg or, for the Wistar Kyoto rat kidneys, increased to 150-200 mmHg and, for the spontaneously hypertensive rat kidneys, raised to 200 or 250 mmHg. The results show that the humoral antihypertensive system is present also in spontaneously hypertensive rat kidneys, but is here reset upwards to or even beyond the elevated MAP level. Furthermore, all mean arterial pressure reductions caused by high-pressure perfusion of Wistar Kyoto and spontaneously hypertensive rat kidneys were accompanied by reductions in heart rate (HR) in the 'donors', in agreement with previous observations after reversing renal hypertension and after i.v. medullipin I injection. In fact, in spontaneously hypertensive rat kidneys, the 'incretory' depressor mechanism appears to be more markedly reset upwards than is the 'excretory' depressor mechanism inherent in pressure diuresis with consequent salt-volume elimination. In conclusion spontaneously hypertensive rats, like Wistar Kyoto rats and Wistar rats, have a humoral antihypertensive system in the kidneys, but it is reset upwards even beyond the elevated mean arterial pressure level in spontaneously hypertensive rats. The combination of a depressor response and reduced heart rate in the 'donors' renders further evidence that the medullipins are the principal, though probably not the only, humoral antihypertensive factors released from the cross-circulated kidneys. PMID- 1877352 TI - Effect of felodipine on the myogenic response to dynamic stretch in vascular smooth muscle. AB - In the present experiments we examined the effect of felodipine, a vasoselective dihydropyridine calcium antagonist, on contractile responses to dynamic and static stretch of the isolated portal vein of the rat. Dynamic stretch was applied to the vascular smooth muscle at graded rates (from 0.5-1.5% muscle length s-1). Earlier observations (Johansson & Mellander 1975) of a rate dependent excitation of the vascular smooth muscle by dynamic stretch were confirmed. Addition of felodipine, 3 nM, reduced the spontaneous activity at static lengths to about 50% but resulted in much stronger inhibition of the dynamic stretch responses. Particularly the rate-dependent increase in active force was no longer evident since the response at high rates of passive lengthening was most clearly reduced by felodipine. By contrast, lowering of the extracellular Ca2+ concentration resulted in a comparable attenuation of the spontaneous contractile activity and of the dynamic stretch responses which still showed the typical rate dependence. Therefore, the pronounced inhibition by felodipine of the dynamic myogenic reactivity of the rat portal vein appeared to be a specific effect and not simply related to the overall reduction in contractile activity. We suggest that felodipine, in addition to its inhibition of action potentials and excitation-contraction coupling may exert a special negative influence on the mechano-electrical coupling, i.e. the process that couples dynamic stretch of the vascular smooth muscle to membrane excitation. PMID- 1877353 TI - Passive avoidance conditioning and unitary activity in the basolateral amygdaloid nucleus of the rat. AB - Single unit activity was recorded in the basolateral nucleus of amygdala in rats in a passive avoidance test. Simultaneously, visual control of exploratory behaviour was carried out. Prior to establishing the conditioning, the mean frequency of the unit discharge was 14 Hz (SD = 9) and 1 minute after conditioning this unit activity decreased to values close to zero; later on (24 and 48 hours), a progressive recovery of the discharge was observed. Behavioural changes were also detected. The long term recovery of unit activity follows the time course of the extinction process. The possible significance of these findings is discussed in relation to some of the functional roles of this nucleus. PMID- 1877354 TI - Strenuous prolonged exercise elevates resting metabolic rate and causes reduced mechanical efficiency. AB - Resting O2 consumption, net mechanical efficiency during cycling exercise and excess postexercise O2 consumption (EPOC) was measured in 15 army cadets after 3 or 4 days of continuous simulated combat exercises (estimated energy demand: 40 MJ day-1), no organized sleep and virtually no food intake (stress experiment). They exercised for 30 minutes at a work load corresponding to about 50% of maximal O2 uptake. An identical test using the same absolute work load was repeated when the cadets were completely recovered from the combat course (control experiment). Resting O2 consumption increased by 15% from 279 +/- 7 ml min-1 (control) to 320 +/- 8 ml min-1 (stress, P less than 0.001). Mechanical efficiency decreased from 24.6 +/- 0.4% (control) to 20.9 +/- 0.2% (stress, P less than 0.001). EPOC1h increased from 0.58 +/- 0.41 l (control) to 2.24 +/- 0.2% (stress, P less than 0.05). Glucose infusion during exercise (0.20 g kg-1 body weight) had no effect on mechanical efficiency or EPOC. About 1/5 of the increase in exercise O2 uptake can be explained by a substrate shift from carbohydrates to fat, as evidenced by a reduction in R-value during exercise from 0.90 +/- 0.012 (control) to 0.80 +/- 0.010 (stress). Hence, after severe physical stress combined with sleep deprivation and food restriction, O2 uptake is increased both at rest and during submaximal exercise. PMID- 1877355 TI - Glucose and ketone body turnover in fasting grey seal pups. AB - Concentration and metabolic replacement (turnover) rate of glucose and ketone bodies were determined at intervals during a 52 day postweaning fast in five grey seal (Halichoerus grypus) pups, using bolus injections of radiotracers. Blood glucose was maintained at a high level throughout the fast, while beta hydroxybutyrate increased 26 times from day 3 to day 37, whereafter it by and large was maintained. Glucose replacement rate decreased to 56% of the day 9 value at day 37 and dropped further to only 32% of the day 9 level at day 52 in two seals, while in another 2 seals it increased at this late stage. The average ketone body replacement rate ranged between 8.6 and 13.8 mumols min-1 kg-1, but did not change significantly (P greater than 0.05) during the fasting period. These results suggest a reduced gluconeogenesis from protein and increased production of ketone bodies, which may in part replace glucose as energy source during fasting. PMID- 1877356 TI - Evidence in the sheep for an interaction between systemic angiotensin II and cerebral angiotensinergic mechanisms. PMID- 1877357 TI - Effect of longstanding venous stasis and hypoproteinaemia on lymph flow in the rat tail. AB - This study was performed to provide information on the determinants of lymph flow by comparing the effect of venous stasis and hypoproteinaemia in the rat tail. This low-compliant tissue was chosen in an attempt to induce preferential changes in interstitial pressure or volume. The removal rate (kAlb) of 125I-labelled human serum albumin (I-HSA) injected subcutaneously was monitored with external gamma-counting equipment and used as a measure of lymph flow. Interstitial fluid hydrostatic pressure (Pi) was measured with wick-in-needle technique, and interstitial fluid was collected post mortem by dry wicks. Colloid osmotic pressure of plasma (COPp) and wick fluid (COPi) was measured with a colloid osmometer. In a separate group of experiments, 51Cr-EDTA and [125I]HSA were used to measure the interstitial fluid volume. Venous stasis, induced by bilateral ligation of the external tail veins, increased interstitial fluid hydrostatic pressure from 1.7 to 16 mmHg and kAlb from 0.030 to 0.063 h-1, whereas tail circumference was nearly constant. Interstitial volume averaged 1.17 ml/g dry weight in control animals and 1.27 ml/g during increased venous pressure. Daily injections of aminonucleoside in salt-loaded rats (0.3% NaCl as drinking water) reduced colloid osmotic pressure of plasma from 19.1 to 8.5 mmHg and of wick fluid from 11.2 to 2.9 mmHg, while interstitial fluid hydrostatic pressure increased to 5.2 mmHg. The removal rate of 125I-labelled human serum albumin increased to 0.113 h-1, compared to 0.051 h-1 in salt-loaded controls. The interstitial volume showed a marked increase in salt-loaded hypoproteinaemic rats, 1.75 ml/g dry weight, compared to 1.30 ml/g in salt-loaded controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877358 TI - Burst firing of mesencephalic dopamine neurons is inhibited by somatodendritic application of kynurenate. AB - Midbrain dopamine neurons of the zona compacta substantia nigra (SN) and ventral tegmental area (VTA), giving rise to the nigrostriatal and mesolimbocortical midbrain dopamine pathways, respectively, typically display a spontaneous activity consisting of single spikes and bursts. Previously, intracerebroventricular administration of the excitatory amino acid (EAA) antagonist kynurenate has been shown to inhibit burst firing and induce a regular, pacemaker-like firing of ventral tegmental area midbrain dopamine neurons. In the present experiments, zona compacta substantia nigra and ventral tegmental area midbrain dopamine neurons were recorded in the chloral hydrate anaesthetized male rat. Kynurenate was administered locally, either by micro iontophoresis or by pneumatic (micropressure) ejection. Both forms of local kynurenate application produced an immediate inhibition of burst firing and a slightly increased regularity of firing in both zona compacta substantia nigra and ventral tegmental area midbrain dopamine neurons. The present results indicate that excitatory amino acid nerves tonically modulate midbrain dopamine neuronal burst firing directly on the midbrain dopamine cell bodies, further stressing the importance of excitatory amino acid innervation in the physiological function of midbrain dopamine neurons, particularly in the dynamic aspects involved in the behavioural modulation and pharmacological responses of these psychopharmacologically important neurons. PMID- 1877359 TI - Cardiac cell membrane repolarization is required for onset of mechanical restitution in papillary muscle. AB - In 10 voltage clamped ferret papillary muscles at 37 degrees C (single sucrose gap), the duration of resting (diastolic, holding) potential was varied in order to define the mechanical restitution process. Following a period of steady state voltage clamp depolarizations to +20 mV, a single test depolarization clamp of 200 or 500 ms duration was introduced. Then, the following period at resting (holding) potential was varied. All the mechanical restitution curves for the 500 ms clamps were delayed by 300 ms compared with the 200 ms clamps. When mechanical restitution was plotted as the relationship between contractile force and test electrical diastolic interval, all processes started from zero interval (i.e. the time of repolarization). Variation of diastolic holding potential between -70 mV and -40 mV did not affect the starting time, but the final force values at full restitution were approached faster and were higher for -70 mV than for -40 mV. There was an inverse relationship between force and second inward current during mechanical restitution after an initial phase of restitution of current. Mechanical restitution is postulated to be due to passage of contractile calcium with time from an uptake to a release compartment within the sarcoplasmic reticulum. Thus the rise of contractile force with increasing test cycle duration should have been independent of whether a 200 or 500 ms depolarization was used. In order to accommodate the discrepancy, we postulate either that (1) sarcoplasmic reticulum calcium release channels require sarcolemmal repolarization to begin to be reactivated or (2) that trigger calcium (calcium induced calcium release from the sarcoplasmic reticulum) is derived from the sarcolemma. PMID- 1877360 TI - Cigarette smoke-induced changes in guinea-pig airway responsiveness to histamine and citric acid. AB - The effect of 50 min cigarette smoke exposure on airway responsiveness to the bronchoconstrictor and tussive effects of histamine and citric acid has been examined in guinea-pigs. Intravenous histamine increased intratracheal pressure (ITP) in anaesthetized guinea-pigs and the dose-response curve was significantly (P less than 0.05) steeper in cigarette smoke- than in air-exposed animals. ED50 values were 11.4 nmol kg-1 (7.4-16.8, 95% confidence interval) and 42.5 nmol kg-1 (28.8-61.4, 95% confidence interval), respectively (P less than 0.05) in smoke- and air-exposed guinea-pigs indicating an enhanced reactivity. However, the sensitivity to intravenous histamine was not changed by the cigarette smoke exposure, and the maximum increase in intratracheal pressure was the same as in control animals (air: 247 +/- 21%, n = 4; smoke: 223 +/- 18%, n = 7). The cigarette smoke-induced hyperresponsiveness to intravenous histamine was not altered by pretreatment with nebulized lidocaine (0.20 M), ipratropium bromide (0.30 mM) or cromoglycate (0.06 M), suggesting that a neural reflex is unlikely to be involved in the development of hyperresponsiveness. Conscious, smoke exposed guinea-pigs had a significantly (P less than 0.001) reduced responsiveness to citric acid (0.40 M) and cigarette smoke. Both cough and bronchoconstriction were suppressed for about 1 h, but unchanged 24 h after exposure. The hyporesponsiveness to citric acid was inhibited by atropine (1.4 mumol kg-1 i.p.) and may therefore, at least in part, be due to increased airway secretions. The present data demonstrate that inhalation of cigarette smoke may alter guinea-pig airway responsiveness to tussive and bronchoconstrictor stimuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877361 TI - Interaction between antisecretory opioid and sympathetic mechanisms in the rat small intestine. AB - The putative existence of an endogenous opioid antisecretory mechanism in the small intestine was tested in anaesthetized Sprague-Dawley rats. Cholera secretion was elicited with cholera toxin and net fluid secretion was measured in vivo using a gravimetric technique allowing on line registrations. Opioid blockade with naloxone (10 mg kg-1 i.v.) increased the cholera secretion significantly but had no effect on control absorption. Pretreatment with phentolamine (2 mg kg-1 i.v.) eliminated the effect of opioid blockade indicating an interaction between the opioid and the adrenergic mechanisms. The effect of naloxone on cholera secretion was unchanged after acute division of the sympathetic nerves to the intestine and removal of the adrenals. Chronic sympathetic denervation of the small intestine, on the other hand, abolished the effect of opiate blockade on the secretion. The antisecretory effect of sympathetic nerve stimulation was unchanged by opiate blockade. CONCLUSION: An intrinsic antisecretory opioid mechanism has been demonstrated in the small intestine of the rat. This endogenous opioid mechanism seems to decrease secretion indirectly via peripheral activation of the sympathetic antisecretory system. PMID- 1877362 TI - Effects of cervical sympathetic nerve stimulation and neuropeptide Y (NPY) on cranial blood flow in the cat. AB - Effects of cervical sympathetic nerve stimulation (SNS) at 10 Hz and intravenous infusion of neuropeptide Y (NPY), 10 and 100 pmol x kg body wt-1 x min-1 for 5 min, on regional blood flow in the cat were investigated with radioactive microspheres. Sympathetic nerve stimulation caused significant reductions in blood flows in the facial tissues including the eye. Alpha-adrenoceptor blockade with phenoxybenzamine and combined beta- and alpha-adrenoceptor blockade with propranolol and phenoxybenzamine abolished the effects of sympathetic nerve stimulation in most facial tissues except in the tongue, upper eyelid and masseter muscle. In most cranial tissues, neuropeptide Y reduced regional blood flow and increased vascular resistance. No effect of neuropeptide Y on vascular resistance was observed in the choroid. In the present study, evidence for a non adrenergic component in sympathetic vasoconstriction was found in the tongue, upper eyelid and masseter muscle but not in the majority of feline facial tissues. Neuropeptide Y was a potent vasoconstrictor in many cranial tissues, while in parts of the uvea, the effects of neuropeptide Y were less pronounced. PMID- 1877363 TI - The effect of meal size on postprandial increase in cardiac output. AB - Heart rate, stroke volume, cardiac output and mean arterial blood pressure were followed from the resting pre-meal situation and for 2 hours after intake of standardized meals in four healthy individuals. Continuous records of stroke volume and cardiac output were achieved with an improved method of Doppler ultrasonography. A smallish meal and one 2 1/2 times larger were both given twice and in random order to each of the four test persons. The consumption of a meal invariably resulted in a cardiac output increase, which developed gradually to reach a maximum level 30 to 60 min after end of the meal. The postprandial cardiac output increase resulted from significant increases in both heart rate and stroke volume. There were distinct and significant differences between the circulatory responses to small and large meals. The increase in cardiac output after a large meal was considerably larger and lasted for longer than the increase after a small meal. Two hours after a small meal cardiac output was nearly or fully back to pre-meal values, while cardiac output was still markedly elevated 2 hours after a large meal. Consequently, the total 'extra' amount of blood delivered by the heart over 2 post-meal hours was significantly--about 100% -larger after the large meal than after the small one. Mean arterial blood pressure either fell or remained almost unchanged in the hour after a meal, so that total peripheral resistance was consistently and significantly reduced in the postprandial period--and considerably more so after a large meal than after a small one. PMID- 1877364 TI - Pulmonary vascular pressure profile in adult ferrets: measurements in vivo and in isolated lungs. AB - We have determined the vascular pressure profile in lungs of adult ferrets utilizing an anaesthetized open chested preparation and have compared the pressure profile in vivo with that in isolated, perfused lungs. Ten adult ferrets, mean body weight 980 +/- 108 g, were studied. For in vivo measurements, five ferrets were anaesthetized, mechanically ventilated and the left chest wall resected. Pressures were measured in the pulmonary artery, left atrium and by micropuncture, in 20-50 microns diameter subpleural arterioles and venules. During micropuncture, ventilation was stopped for 1-2 min and the lungs kept distended at an airway pressure of 6 cmH2O. Left atrial pressure was raised to approximately 8 cmH2O with saline infusion so that lungs were in Zone 3. Cardiac output was measured by thermodilution. Lungs of five other ferrets were isolated and perfused with a steady flow roller pump. In these lungs blood flow was adjusted so that pulmonary artery pressure was similar to that in anaesthetized ferrets, with airway and left atrial pressures at 6 and 8 cmH2O respectively (Zone 3). Blood haematocrit (35 +/- 7%) was similar in the two groups. In lungs of anaesthetized ferrets total arteriovenous pressure drop was 12.1 +/- 1.9 cmH2O, with cardiac output being 210 +/- 80 ml kg body weight-1 min-1. Fractional resistance in arteries was 37%, 37% in microvessels and 26% in veins. In isolated ferret lungs, though blood flow was only 48 +/- 10 ml kg body wt-1 min-1 for the same total arteriovenous pressure drop as in vivo, the longitudinal distribution of vascular resistance was similar to that in live ferrets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877365 TI - A comparison of laser Doppler flowmetry with the radiolabelled microsphere reference flow technique to measure tracheal blood flow in dogs. AB - Measurements of tracheal wall blood flow were made in anaesthetized, ventilated dogs during resting ventilatory conditions, during application of positive end expiratory pressure (PEEP) and during eucapnic hyperventilation of dry air, using laser Doppler flowmetry and the radiolabelled microsphere reference flow technique. Six regions of the trachea were studied in each dog, and the average laser Doppler flowmetry measurement derived from 12 sites within each region was compared with the reference flow measurement, obtained using 15 microns diameter microspheres labelled with 113Sn, 103Ru, 141Ce or 151Gd. Under each set of ventilatory conditions, there was a weak, but significant, correlation between laser Doppler flowmetry and reference flow values (baseline r = 0.44, hyperventilation r = 0.44, and PEEP r = 0.74). Average laser-Doppler flowmetry and reference flow values showed a similar reduction from baseline during application of PEEP. The mean (SD) change from baseline, expressed as a percentage, was -63 (15)% for laser-Doppler flowmetry values, and -63 (21)% for reference flow values. However, there was no correlation between the magnitude of change measured in individual regions using the two techniques. During hyperventilation, laser Doppler flowmetry measurements showed variable changes from baseline, and the mean change was -12 (45)%, which was not significantly different from zero. Reference flow values increased during hyperventilation, the mean change being 87 (77)%. The results indicate that laser Doppler flowmetry and reference flow measurements of airway wall blood flow are not directly comparable. PMID- 1877366 TI - Potassium homeostasis during and following exhaustive submaximal static handgrip contractions. AB - The aim of the present study was to follow local potassium homeostasis during and after exhaustive contractions. Eight subjects performed static handgrip with their right forearm at 10%, 25% and 40% maximal voluntary contraction. Blood flow (venous occlusion plethysmography) and the venous effluent plasma potassium concentration were followed during the contractions and during a 60-min recovery period. Electromyography was registered during exercise (frequency analysis). With all three protocols the blood flow increased significantly during the contractions and the same was true of the effluent plasma potassium concentrations. In the recovery period blood flow and the venous effluent plasma potassium concentration returned to base values within 30 min following 40% maximal voluntary contraction while following 10% and 25% maximal voluntary contraction, venous effluent plasma potassium concentration was still significantly below resting values one hour after the exercise had ceased, indicating a long-lasting uptake of potassium from the blood into the muscles. In line with this a significant potassium deficit was still seen after 1 hour of recovery following 10% and 25% maximal voluntary contraction. It is concluded that the recovery of potassium homeostasis following prolonged low-intensity contractions is a slow process. This may be due to either sequestration of potassium in other tissues with a subsequent slow release and/or insufficient sodium/potassium pump activation. The contraction induced potassium loss may play a major role in muscle performance since it may impair mechanical force production, and it is hypothesized that this may be the origin of low-frequency fatigue. PMID- 1877367 TI - Potential-dependent potassium currents in the rapidly adapting stretch receptor neuron of the crayfish. AB - The outward current was analysed in the rapidly adapting stretch receptor neuron of the crayfish Pacifastacus leniusculus with a two-micropipette potential clamp technique and K(+)-selective microelectrodes in an attempt to establish if the properties of this current could explain the difference in adaptive behaviour compared to the slowly adapting receptor. A fast activating outward current carried by K+ was revealed. The time constant of activation(tau n) was dependent on potential and had a mean value of 0.5 ms at potential steps to 0 mV. Activation followed a second-order process according to the Hodgkin-Huxley model. The potential dependence of activation (n infinity) followed by a sigmoid curve n infinity = 1/(1 + exp/[(E - En)/a]) with a half maximal activation potential En = -44 mV and a = -13 mV. When long pulses were applied the outward potassium current decreased with two time constants, one that was potential independent (0.2 s) and one that was potential dependent (2-8 s). The latter could be explained by accumulation of K+ in the extracellular space of the neuron. The potential dependence of inactivation followed a sigmoid function infinity = 1/(1 + exp[(E - Ek)/+a]) with Ek = -36 mV and a = 13 mV. The inactivation properties are different from those of the classical fast transient (IA) current. The transport system for the outward potassium current during depolarizing potential steps in the rapidly adapting stretch receptor is similar to the current found in the slowly adapting receptor neuron. However, the activation is faster and seems to occur at potentials more negative than in the slowly adapting receptor. These differences can contribute to but not entirely explain the difference in adaptive behaviour between the slowly and rapidly adapting receptor. PMID- 1877368 TI - Extracellular levels of adenosine and its metabolites in the striatum of awake rats: inhibition of uptake and metabolism. AB - The level of purines in the striatum of awake, freely moving rats was studied using microdialysis. The calculated extracellular concentration of adenosine and its metabolites inosine and hypoxanthine was very high immediately after implantation of the dialysis probe but decreased within 24 h to a level which remained stable for two days. Using in vitro calibration to determine the relative recovery of the dialysis probes we estimated resting levels in the striatal extracellular space to be 40, 110 and 580 nM, respectively. Inhibition of adenosine deaminase by deoxycoformycin produced a significant 1.4-fold increase in extracellular adenosine levels and a fall in inosine and hypoxanthine. A combination of three uptake blockers (dipyridamole, lidoflazine and nitrobenzylthioinosine), caused a 4.5-fold increase in extracellular adenosine levels without any change in inosine or hypoxanthine levels. After uptake inhibition deoxycoformycin did not have any significant effect. The present results show that the microdialysis technique can be used to determine levels of purines in the extracellular fluid of defined brain regions in awake animals. The high levels recorded during the first several hours after implantation may be artefactually high and reflect trauma. The results also show that adenosine levels can be altered in vivo by inhibitors of adenosine transport and adenosine deaminase. The present results indicate that the physiological adenosine level in striatal extracellular space is in the range 40-460 nM. PMID- 1877369 TI - Low ambient temperature increases baroreflex-governed sympathetic outflow to muscle vessels in humans. AB - Microelectrode multi-unit recordings of muscle nerve sympathetic activity, primarily involved in blood pressure regulation, were made from the right peroneal nerve in 10 healthy subjects during exposure to cold inside a box used for hypothermic surgery. Blood pressure was monitored by an automatic cuff applied to the left arm. Heart activity (ECG) and the temperature inside the box were monitored. Muscle nerve sympathetic activity outflow and blood pressure were stable during 15 minutes initial rest at 22.7 +/- 0.3 degrees C (mean +/- SEM). All subjects increased muscle nerve sympathetic activity and blood pressure with lowering of ambient temperature. The box temperature was 10.5 +/- 0.3 degrees C at the end of the cooling period. With rewarming the changes in muscle nerve sympathetic activity and blood pressure were reversed. Mean outflows of muscle nerve sympathetic activity during initial rest, final phase of cooling period, and post-rewarming were 20.3 +/- 2.7, 26.6 +/- 3.2 and 20.2 +/- 2.8 burst min-1, respectively. Systolic blood pressure during the same periods was 118 +/- 3, 131 +/- 4 and 120 +/- 4 mmHg, respectively, whereas corresponding values for diastolic blood pressure were 73 +/- 2, 82 +/- 2 and 75 +/- 2 mmHg (P less than 0.001 for all variables; (ANOVA). It is concluded that muscle nerve sympathetic activity, while not regarded as being involved in body temperature regulation, is under the influence of ambient temperature and contributes to blood pressure elevation in a cold environment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877370 TI - The action of 2,3-butane-dionemonoxime on the inotropic state in guinea-pig myocardium. AB - Isolated papillary muscles from guinea-pig right ventricles were used (temperature 33 degrees C, stimulation frequency 0.5 Hz). Isometric twitch and action potentials were recorded. Upon addition of 2,3-butane-dionemonoxime (BDM) (2 mM) the peak twitch force was reduced from 4.17 +/- 0.4 mN/mm2 to 1.68 +/- 0.3 mN/mm2 (n = 9, P less than 0.001). The time course of the isometric twitch was slightly altered. Time to peak tension (TPT) was reduced by 12.0 +/- 3% (n = 9, P less than 0.001) whereas time to half relaxation (THR) was left unaffected. The rate of rise of force was reduced by 35 +/- 3.2 mN/mm2s i.e. 46 +/- 3%. The action potential duration and amplitude was not significantly changed by the drug. The shape of the curve relating peak twitch force of an extra beat to the preceding test interval, i.e. mechanical restitution, was affected by 2 mM 2,3 butane-dionemonoxime. The curve reached its maximum faster after addition of the drug. Maximum postextrasystolic potentiation (force in response to the prepreceding test interval) was 3.2 +/- 0.4 mN/mm2 in 2 mM 2,3-butane dionemonoxine and 7.6 +/- 0.7 mN/mm2 in control (n = 6). However the percentage potentiation was very similar in control (82%) and in presence of 2,3-butane dionemonoxime (91%). Peak twitch force in relation to peak force of the preceding potentiated contraction during decay of postextrasystolic potentiation was analysed. There was a linear relation between the variables, the slope being 0.34 +/- 0.04 in control and 0.30 +/- 0.02 in 2,3-butane-dionemonoxime. This suggests that the drug is without an action on the fraction of calcium recirculating within the cell.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877371 TI - Lesions of bulbo-spinal serotonergic or noradrenergic pathways reduce nociception as measured by the formalin test. AB - Intrathecal administration of the neurotoxins 5,6-dihydroxytryptamine (5,6-DHT) and 6-hydroxydopamine (6-OHDA) in rats selectively lesioned the descending spinal serotonergic and noradrenergic pathways, respectively. Four days after neurotoxin administration the behaviour was evaluated in the formalin test. Several behavioural variables were recorded. The statistical analysis of the results was supplemented using a multivariate statistical method (partial least squares projection to latent variables, PLS) in addition to traditional analysis of variance. The described methods for recording and statistical analysis of behaviour appear to be useful in describing drug-induced differences in behavioural patterns in the formalin test. Both types of lesion reduced the pain related behaviour in the formalin test (protection of the paw, biting and licking). The results indicate that the descending monoaminergic pathways are parts of a network which maintains adequate nociceptive responses to a chemical stimulus, or to stimuli lasting several minutes, as in the formalin test. PMID- 1877372 TI - The microsphere technique in anaesthetized and awake pregnant guinea-pigs: reproducibility of repeated blood flow measurements. AB - Repeated microsphere injections are extensively employed for measurements of uteroplacental blood flows in experimental animals. However, this technique has not been systematically validated in pregnancy. In the present series of experiments the effects of three consecutive microsphere injections on central haemodynamics and regional blood flows were studied in 43 late pregnant guinea pigs. In group A (n = 13) experiments were carried out in the awake chronically catheterized animal. In group B (n = 8) animals were studied under anaesthesia. In two additional anaesthetized groups reference withdrawal rate (C, n = 7) and the amount of injected spheres (D, n = 7) were increased 2-3 fold. Cardiac output, mean arterial blood pressure, heart rate as well as regional blood flows to placenta, ovaries, kidneys, heart, liver and carcass remained unaltered in all protocols. Myoendometrial blood flow increased in group A and C and a similar pattern could be demonstrated in group B and D but was not statistically significant. Adrenal blood flow was enhanced in groups A and C and brain blood flow increased in group C and D. The gastrointestinal tract especially the stomach was sensitive to repeated microsphere injections since blood flow reductions were apparent in all groups but were statistically significant only for groups A and D. In group E (n = 8), the three microsphere labels were injected simultaneously. The coefficients of variability for these blood flow measurements were in the range of 3.6-6.8% for different organs. It is concluded that repeated microsphere injection in an ideal method to measure placental blood flow. However, the technique may provide inaccurate results with respect to the myoendometrium and gastrointestinal tract. PMID- 1877373 TI - Decreased insulin-stimulated 3-0-methylglucose transport in in vitro incubated muscle strips from type II diabetic subjects. AB - Peripheral insulin resistance in type II diabetes mellitus has been attributed to alterations in skeletal muscle glucose metabolism. However the direct dose response relationship between insulin and glucose transport has not yet been studied in human skeletal muscle. We investigated 3-0-methylglucose transport in in vitro incubated skeletal muscle strips from eight healthy controls (age 61 +/- 6 yrs) and six lean type II diabetic patients treated with oral antidiabetic medication (age 73 +/- 3 yrs). Rectus abdominis muscle samples (approximately 1 g), obtained during elective abdominal surgery, were clamped at their resting length in vivo, whereupon strips (20-50 mg) were prepared for in vitro incubation. Measurements of high-energy phosphates and glycogen levels revealed that the muscle strips maintained energy levels during the incubation period. Glucose transport responded to insulin in a dose-response manner in the control group, with a 2-fold increase following maximal stimulation. Muscle strips from the diabetic group demonstrated a marked decrease in the insulin dose-response curve (P less than 0.01), when compared to healthy muscle strips. At a maximal insulin concentration (10,000 microU x ml-1), the response of the diabetic muscle tissue was 50% less than that of the healthy control tissue (P less than 0.05). This report demonstrates a dose-response curve for insulin stimulated 3-0 methylglucose transport in in vitro incubated human skeletal muscle strips. Furthermore, in type II diabetic muscle, our results provide evidence for one or several defects at a postreceptor level. PMID- 1877374 TI - The effects of hypobaric hypoxia (50.6 kPa) on blood components in guinea-pigs. AB - One hundred and five male (Hartley) guinea-pigs weighing 350-380 g and 30 splenectomized guinea-pigs were exposed to simulated hypobaric hypoxia of 50.6 kPa (equal to an altitude of 5486 m) for 14 days. The partial pressure of oxygen was set at half that at sea level. The white blood cell count increased significantly on day 3 of the simulated high altitude experiment but returned to normal on day 7, whereas the red blood cell count increased continuously. To study the effect of high altitude exposure on platelets, the platelet count in the splenectomized group was compared to that in a non-splenectomized group. Investigation of the resistance of red blood cell membranes to osmotic pressure under hypobaric conditions revealed a shift of the onset of haemolysis in the hyperosmotic direction. These findings may help to increase our understanding of the biochemical mechanisms of adaptation to hypobaric hypoxia. PMID- 1877375 TI - On the role of polyamines in bone resorption induced by parathyroid hormone. AB - In order to elucidate the possible role of polyamines in the mobilization of mineral from long-term bone cultures stimulated with parathyroid hormone we have measured the activity of ornithine decarboxylase in osteoblasts, the levels of polyamines in calvarial bone and determined the effect of added polyamines and inhibitors of polyamine biosynthesis on calcium mobilization. Parathyroid hormone (10 nmol l-1) stimulated omithine decarboxylase activity by approximately 50% in both cultured bone cells of osteoblastic phenotype, UMR 106 and in mouse calvarial osteoblast-like cells. In mouse calvaria the levels of putrescine and spermidine were increased by parathyroid hormone after 24 hours. The levels of spermine were very low and were unchanged by parathyroid hormone. The two polyamine synthesis inhibitors alpha-difluoromethylornithine (DFMO; 2 mmol l-1) and methylglyoxal-bis-guanylhydrazone (MGBG; 50 mu mol l-1) did not significantly affect the mobilization of 45Ca from parathyroid hormone-stimulated bones. All three polyamines, putrescine, spermidine and spermine, inhibited the mobilization of 45Ca induced by parathyroid hormone in a dose-dependent manner. The inhibition induced by putrescine was reversible. In summary, we have shown that parathyroid hormone increases the accumulation of polyamines in bone, but the effect is small. Furthermore, inhibition of polyamine biosynthesis does not reduce parathyroid hormone-induced mineral mobilization and the addition of polyamines leads to a reduced rather than a stimulated mineral mobilization. Thus, polyamines do not seem to be critically involved in the changes in bone resorption induced by parathyroid hormone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877376 TI - Changes in plasma hypoxanthine and free radical markers during exercise in man. AB - Eight men cycled for about 6 minutes at workloads corresponding to 44 and 72% of maximal oxygen uptake and to fatigue at 98% maximal oxygen uptake. Blood samples from a brachial artery and a femoral vein were taken at rest and during exercise. Hypoxanthine, xanthine and urate in plasma were significantly elevated at fatigue and after 10 minutes of recovery. Only hypoxanthine showed a significant arterio femoral venous difference. The release of hypoxanthine from the legs increased during the recovery period and was three-fold higher 10 minutes post exercise than at the end of exercise. It is concluded that the marked increase in plasma hypoxanthine which occurs during intensive exercise originates from the working muscle whereas the transformation to xanthine and urate may occur in other tissues. Glutathione, methemoglobin and malondialdehyd (MDA) were used as plasma markers of free radicals. Total glutathione (glutathione + glutathionedisulfide) in blood and plasma increased during intensive exercise and may be indicative of free radical formation. However, MDA was not detectable in plasma during any conditions (less than 0.1 mumol x l-1 plasma) and methemoglobin decreased slightly during exercise. Further studies using more specific techniques are required to determine whether the formation of free radicals is increased after brief intensive exercise. PMID- 1877377 TI - Intracellular cytosolic free calcium concentration in the macula densa and in ascending limb cells at different luminal concentrations of sodium chloride and with added furosemide. AB - The juxtaglomerular apparatus fulfils several important regulatory functions in the kidney, such as tubuloglomerular feedback (TGF) control and control of renin release. The macula densa (MD) cells sense the fluid load by perceiving the distal NaCl concentration via a Na-K-2Cl cotransport system in the luminal cell membrane. It has been proposed that macula densa cell activation may involve changes in intracellular cytosolic free calcium concentration ([Ca2+]i), as one link in the chain of events activating TGF or releasing renin. We therefore investigated the changes in the intracellular calcium concentrations with fura-2, using a video system, in macula densa cells, and compared them with the changes in the corresponding concentrations in the ascending limb of the loop of Henle (c TAL). The results show that our technique for analysing intracellular cytosolic free calcium in isolated perfused tubules is valid for this purpose, and the Kd value obtained was similar to that found by Grynkiewicz et al. (1985). The intracellular cytosolic free calcium concentration was about 90 nM both in the macula densa and c-TAL cells, and the macula densa cell intracellular cytosolic free calcium concentration increased by about 20 nM when the tubular lumen was perfused with Na and Cl at low concentrations. No significant changes were noted when furosemide was added to the perfusion solutions. We consider it hardly likely that this small change in intracellular cytosolic free calcium concentration can be entirely responsible for full activation of renin release or full inactivation of the TGF control mechanism. It would seem that the signal transmission from the macula densa cells could occur by other routes than through activation of intracellular cytosolic free calcium concentration. PMID- 1877378 TI - Total muscle NADH during 30-min submaximal exercise: effects of endurance training. PMID- 1877380 TI - Microbial cytochromes P-450 and xenobiotic metabolism. PMID- 1877379 TI - Microbial transformations of herbicides and pesticides. PMID- 1877381 TI - Foodborne yeasts. PMID- 1877382 TI - High-resolution electrophoretic purification and structural microanalysis of peptides and proteins. PMID- 1877383 TI - An environmental assessment of biotechnological processes. PMID- 1877384 TI - Fate of recombinant Escherichia coli K-12 strains in the environment. PMID- 1877385 TI - Patterns of divergence in homologous proteins as indicators of secondary and tertiary structure: a prediction of the structure of the catalytic domain of protein kinases. AB - The secondary structure and elements of tertiary structure have been predicted for the catalytic domain of protein kinases using a method that extracts structural information from the patterns of conservation and variation in an alignment of homologous proteins. The central features of this structural prediction are: (a) the catalytic domains of protein kinases do not incorporate a Rossmann fold; (b) the core of the structure is founded on beta sheets built from pairs of bent antiparallel beta strands; (c) five helices, including an especially long helix (alignment positions 129-152) that lie on the outside of the folded core. These proteins are important in many aspects of metabolic regulation. PMID- 1877386 TI - Thymidylate synthase inhibitors: the in vitro activity of a series of heterocyclic benzoyl ring modified 2-desamino-2-methyl-N10-substituted-5,8 dideazafolates. AB - Heterocyclic para-aminobenzoate modifications of 2-desamino-2-methyl-5,8 dideazafolic acid and a series of its N10-substituted analogs have produced a number of interesting compounds that have enabled a deeper understanding of the biochemical events required for activity in this class of antimetabolite. There is a relationship that has become apparent between compound potency and both uptake via the reduced-folate carrier and FPGS substrate activity. Rapid cellular uptake and metabolism of polyglutamate forms that are approximately 100-fold more potent as inhibitors of TS can translate a modest TS inhibitor such as ICI D1694 into a very potent inhibitor of cell growth (approximately 500- and approximately 10-fold more potent than CB3717 or ICI 198583, respectively). Polyglutamation may therefore act as an almost essential activation step and ICI D1694 may be highly specific for tumors expressing both the reduced-folate carrier and FPGS. Polyglutamation of folate analogs also leads to drug retention which may play a major role in the pharmacodynamics of TS inhibition by ICI D1694 in vivo. Current studies with 3H-ICI D1694 are aimed at demonstrating metabolism to polyglutamates in tumor cells. The serious toxic limitations of CB3717, i.e., liver and kidney toxicities, are not seen with ICI D1694 reflecting the good water solubility of the drug compared with CB3717. The toxicities observed in mice are however to hematological tissues and are due to its TS inhibitory effects. Thus ICI D1694 may elicit toxicities in man more typical of an antimetabolite than of CB3717. The clinical evaluation of ICI D1694 may further our understanding of the role that metabolism to polyglutamates may have in therapeutic activity. PMID- 1877387 TI - Regulation of gene expression by insulin. AB - Insulin after binding to its plasma membrane receptor regulates many cellular processes as well as the expression of several genes. These effects of insulin can be temporarily classified as short-term (minutes) and long-term (hours-days). The different steps of gene expression that may be under insulin control are reviewed. The main focus of the review is on the regulation of gene transcription by insulin. A putative insulin negative regulatory sequence is proposed based on the comparison of the 5'-upstream regions of the phosphoenolpyruvate carboxykinase and protein disulfide isomerase genes and compared with a recently identified positive insulin regulatory element located in the 5'-upstream region of the glyceraldehyde-3-phosphate dehydrogenase gene. PMID- 1877388 TI - The biological significance of lipoprotein lipase modulation by phenobarbital and heparin. AB - When confluent cultures of 3T3 F442A cells were treated with insulin, differentiation occurred within 6 days as indicated by LPL secretion followed by increased intracellular levels of protein and triacylglycerol. PB increased LPL secretion 2- to 3-fold and intracellular LPL 3- to 10-fold in a time-dependent manner; these increments were less in proportion to the length of the time interval between confluence and initiation of PB treatment. These results are consistent with the notion that PB promotes conversion of adipocyte precursors to mature adipocytes by increasing the proportion of the former that become susceptible to the differentiating stimulus. Human subjects treated with heparin by continuous i.v. infusion over 4 days showed an initial decrease in serum triacylglycerol concentration in response to the initial bolus injection, accompanied by sharp increases in circulating LPL and HTGL, but the triacylglycerol concentration returned to normal within 24 hr. Rats infused with heparin by means of peritoneal implantation of osmotic minipumps demonstrated dose-dependent increases in circulating LPL, accompanied by reduction in heart muscle LPL but inconsistent changes in other tissues examined. Heparin had no effect on the clearance of circulating LPL but did reduce the total body pool of endothelial-bound enzyme. No changes in fasting triacylglycerol and free glycerol were observed, but exogenous VLDL were cleared at a faster rate in heparinized animals. Since the latter also manifested a decrease in de novo fatty acid synthesis, it seems that the heparinized rat is able to maintain circulating levels of triacylglycerol by efficient re-esterification of preformed fatty acids despite the enhanced lipolysis consequent upon higher plasma LPL activity. PMID- 1877389 TI - Application of metabolic-control logic to fuel utilization and its significance in tumor cells. AB - The importance and the value of applying metabolic-control logic to the question of fuels, their rates of utilization and their significance to the process of proliferation are presented. Application of the recently developed quantitative theory of metabolic control of branched pathways provides a hypothesis to account for the high rate of both glycolysis and glutaminolysis in lymphocytes, macrophages and, in particular, in tumor cells. Both glycolysis and glutaminolysis provide metabolic intermediates for biosynthetic pathways: for example, glucose-6-phosphate for the formation of ribose-5-phosphate, and glutamine, ammonia and aspartate which are required for the synthesis of purine and pyrimidine nucleotides. However, the rates of both glycolysis and glutaminolysis are greatly in excess (greater than 400-fold) of the requirements for the biosynthetic processes. If energy formation per se was the major reason for the high rate of glutamine utilization, why is the oxidation only partial? The ability of the cell to divide will require the synthesis of all the DNA, RNA, phospholipids, etc., at precise times in the cell cycle. Hence very high and accurate sensitivity of the processes that provide the precursors for these compounds to their specific regulators will be expected. Maintenance of high rates of glycolysis and glutaminolysis at all times can be seen therefore as a device to allow intermediates to be "tapped off" at the precise rate required whenever they are needed for biosynthesis. Maximal activities of some key enzymes of glycolysis, the tricarboxylic acid cycle and glutaminolysis from a variety of normal, neoplastic and suppressed cells are presented. The relative activities of hexokinase and 6-phosphofructokinase suggest that, particularly in neoplastic cells, in which the capacity for glucose transport is high, hexokinase could approach saturation in respect to intracellular glucose; consequently, hexokinase and phosphofructokinase could play an important role in the regulation of glycolytic flux in these cells. The activity of pyruvate kinase is considerably higher in tumorigenic cells than in nontumorigenic cells and higher in metastatic cells than in tumorigenic cells: for nontumorigenic cells the activities range from 28.4 to 574, for tumorigenic cells from 899 to 1280, and for metastatic cells from 1590 to 1627 nmol/min per mg of protein. The ratio of pyruvate kinase activity to 2 x phosphofructokinase activity is very high in neoplastic cells. The mean is 22.4 for neoplastic cells, whereas for muscle from 60 different animals it is only 3.8.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1877391 TI - Structural and functional diversities of a family of signal transducing protein kinases, protein kinase C family; two distinct classes of PKC, conventional cPKC and novel nPKC. AB - Recent molecular cloning and biochemical experiments on the nature of protein kinase C (PKC) have revealed the existence of two distinct classes of phorbol ester (and diacylglycerol) receptor/protein kinase, conventional PKC (cPKC) and novel PKC (nPKC). Each of these classes contains multiple related molecules expressed in tissues and cells in a type-specific manner. Although nPKC does not show the typical PKC activity ascribable to conventional PKCs and thus was neglected in earlier studies, several lines of evidence suggest that nPKCs are involved in a variety of cell responses to physiological stimuli and phorbol esters. It is possible that in some cases nPKC is the major mediator of the so called PKC-activators, such as phorbol esters, mezerein, and bryostatins. In addition to the clear difference between cPKC and nPKC, functional diversity among conventional PKCs has also been demonstrated; PKC gamma differs in its competence to mediate the signal toward transcriptional activation through TPA responsive cis-acting elements from cPKC alpha and nPKC epsilon. The differences between cPKC and nPKC and among the individual members of each of these two classes, and their specific pattern of distribution in tissues and cells, provide a rationale by which to explain the specificity and diversity of cellular responses to external stimuli generating DAG and to phorbol esters. The results presented here also provide a means to dissect the complex signaling pathway in cells and to analyze the molecular basis underlying the signal transduction processes mediated by this family of protein kinases. PMID- 1877390 TI - Alternative splicing is an efficient mechanism for the generation of protein diversity: contractile protein genes as a model system. AB - Alternative splicing has emerged in recent years as a widespread device for regulating gene expression and generating protein diversity. Its analysis has provided some mechanistic understanding of this form of gene regulation and, in addition, has provided new insights into some fundamental aspects of splicing. This mode of regulation is particularly prevalent in muscle cells, where genes such as troponin T are able to generate up to 64 different isoforms from a single transcriptional unit. Alternative splicing has the potential to raise the coding capacity of the small multigene families that code for the contractile proteins so that several million structurally different sarcomeres can be generated. The mammalian alpha-tropomyosin gene has proved particularly useful for the analysis of the mechanisms involved in this type of regulation. In particular, the mutually exclusive splicing of exons 2 and 3 has provided answers about the processes involved in the three main regulatory steps: (a) establishment of mutually exclusive behavior; (b) the elements involved in setting up the default pattern of splicing, and (c) the switch from the default to the regulated splicing pattern in some cell types. PMID- 1877392 TI - Construction and chemotherapeutic potential of carboxypeptidase-A/monoclonal antibody conjugate. AB - Carboxypeptidase-A and a monoclonal antibody (KS1/4) directed against a human lung carcinoma cell line (UCLA-P3) were derivatized by treatment with succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate and N-succinimidyl 3 (2-pyridyldithio)propionate, respectively. Admixture of these entities produced a stable conjugate containing 4 to 5 enzyme molecules per molecule of antibody. The conjugate (Mr approximately equal to 300 kDa) was purified to homogeneity by HPLC gel filtration and HPLC ion-exchange chromatography. Neither the catalytic activity of the enzyme nor the antigen-binding capacity of the monoclonal antibody was impaired in the conjugate. UCLA-P3 cells that had been exposed to the conjugate and then washed thoroughly were extremely sensitive to methotrexate alpha-alanine (MTX-Ala), a prodrug form of MTX. At 10(-5) M, MTX-Ala was almost as effective as free MTX in blocking the replication of conjugate-treated cells. These results demonstrate the chemotherapeutic potential of enzyme-monoclonal antibody conjugates used in conjunction with prodrugs. PMID- 1877393 TI - Platinum coordination complexes which circumvent cisplatin resistance. AB - In the search for a platinum complex capable of oral administration, the poor bioavailability of established drugs has been circumvented by the discovery of a novel class of platinum (IV) ammine/amine dicarboxylate dichlorides. These compounds, when administered orally to mice carrying the ADJ/PC6 plasmacytoma, exhibit antitumor selectivities far superior to those of cisplatin or carboplatin (given intraperitoneally). Oral activity comparable to that of intraperitoneal cisplatin and carboplatin has also been demonstrated in a panel of human ovarian tumor xenografts. Platinum (IV) ammine/amine dicarboxylates retain cytotoxicity in cultures of L1210/cisplatin and L1210/tetraplatin acquired resistant cells. This property does not translate into a cisplatin-resistant variant of the ADJ/PC6 tumor, in the example of JM221. This result reflects experience with tetraplatin, a drug currently in phase I study, which is comparably ineffective against an ADJ/PC6/cisplatin variant. It is a moot point whether either L1210 or ADJ/PC6/cisplatin-resistant variants are clinically predictive screening models, since this issue must be determined ultimately by clinical study. We have attempted to resolve this dichotomy through the establishment of human ovarian carcinoma lines, both in vitro and in vivo, where there is evidence that response to platinum coordination complexes in the several models reflects that of the donor patient's tumor to platinum-based clinical therapy. The data herein for platinum (IV) ammine/amine dicarboxylates in these models gives encouragement to the notion that these novel compounds may be of value as oral therapeutic agents, whilst also providing an important lead to the discovery and development of a new generation of platinum drugs possessing broad clinical utility. PMID- 1877394 TI - Enhanced expression of the cellular oncogene MYCN and progression of human neuroblastoma. AB - A central issue in cancer research is how tumors evolve and acquire a more aggressive phenotype. It is a widely discussed hypothesis that tumor cell populations progress by evolutionary change as a result of the generation of a variant cell through genomic instability followed by selection of particular variant clones having a growth advantage within the particular tissue environment. Genetic instability appears to be characteristic of neoplastic cells, but no consistent increase in instability seems to accompany progression of the malignant phenotype of the tumor. It is reasonable to assume that quantitative or qualitative changes of cellular oncogenes contribute to the emergence of more malignant phenotypes. Although any one of the molecular changes of cellular oncogenes identified over the past years is a good candidate as an element in progression, amplification appears particularly frequently as a correlate to advanced tumor stage. The fact that amplification does not show up in all progressing tumors of a particular type, for instance in only 50% of advanced-stage neuroblastomas, is often construed as speaking against a role in progression. One should be aware, however, that it is the enhanced expression of a gene consequent to amplification and not amplification per se that affects the cellular phenotype. There are alternative molecular pathways by which expression of a particular gene may become deregulated. During the past decade much information has accrued about genetic alterations in tumor cells. The activation of the oncogenic potential of cellular genes can take different routes among which mutational alteration, translocation and amplification predominate. In particular, amplification has found its way to practical use due to its association with more aggressively growing types of human cancer. MYCN amplification in neuroblastoma is a paradigm for the prognostic significance of oncogene alteration, and at the same time has represented the clinical debut of oncogene research. The full significance of oncogene amplification as a predictor for poor prognosis became clear with the more recent identification of amplified ERBB2 in aggressively growing breast cancers. The state of the art is that amplified cellular oncogenes define cancer patients who have a poor prognosis and require a specific therapeutic regimen. PMID- 1877395 TI - The heterologous expression of the cytochromes P450: a new approach for the study of enzyme activities and regulation. AB - The superfamily of cytochrome P450s encompasses a vast arena of biologically important reactions. The ever-increasing numbers of P450s and the diversity of their enzymatic properties dictate the need to develop new approaches for studying their chemical, physical and catalytic properties. The heterologous expression of P450s in various cell systems (e.g., COS cells, yeast, E. coli, etc.) now provides a means of producing recombinant proteins for such studies. The example is presented of the expression of P450(17)alpha in COS cells and the use of this technique for the comparison of the enzymatic properties of the rat, bovine and human enzymes. Further, studies are described whereby cotransfection results in the simultaneous expression of more than one P450 permitting the construction of 'designer membranes' for assessing protein-protein interactions and the reconstruction of complex pathways of metabolism. Recent advances with genetically engineered systems point to the power of the transfection technique for the study of structure-function relationships with this class of important hemoproteins. PMID- 1877396 TI - Inositol lipid phosphorylation in the cell nucleus. AB - Inositol lipid metabolism has been analyzed in isolated rat liver nuclei and nuclear fractions, in order to determine the subcellular distribution of the sites of lipid phosphorylation and breakdown. Lipid kinases and phosphoesterases appear to be tightly bound nuclear components, and can utilize exogenous substrates administered to membrane-depleted structures. The possible involvement of specific carrier protein in the nuclear metabolism of inositol lipids has also been analysed by studying the uptake and processing of phosphatidylinositol transferred to the isolated nuclei by phosphatidylinositol transfer protein (PI TP). PI-TP greatly stimulates the incorporation of phosphatidylinositol from microsomal membranes and synthetic vesicles, and the lipid taken up is available for phosphorylation and breakdown by enzymes associated to the nucleus. The results obtained support previous data on the metabolic and structural role of nuclear lipids, and suggest that the cell nucleus is a site of lipid phosphorylation, not necessarily involving enzymes and substrates located on the nuclear membrane. They also indicate that an integrated signalling pathway can exist at the nuclear level utilizing inositol lipid-derived second messengers and PKC to control replication and transcription. PMID- 1877397 TI - Hydrophobized antiviral antibodies and antisense oligonucleotides. AB - A method of suppressing virus reproduction in cells has been proposed. The approach consists of affecting the cells with antiviral antibodies artificially hydrophobized with fatty acid residues. Reproduction of influenza viruses in MDCK cells and respiratory-synticial virus in HeLa cells was used as a model to demonstrate that poly- and monoclonal antibodies, modified by 1 or 2 stearic acid residues, are potent, unlike the non-modified antibodies, at inhibiting viral reproduction. The observed phenomenon is apparently due to penetration of hydrophobized antibodies into the cells. Thus, in particular, considerable antiviral activity is exhibited by monoclonal antibodies against NP-protein of influenza virus, which is an antigen accessible to antibodies only inside the infected cells. Hydrophobized antibodies do not affect the kinetics of viral protein synthesis; they block the virus withdrawal from the cells, probably by interfering with the assembling and budding of virus particles. To enhance penetration of oligonucleotides ("oligos") into cells, chemical modification of the former at the 5'-end phosphate group by fatty radicals has been suggested. The undecanol-modified oligo namely an oligo complementary to the protein binding sites located at the influenza virus polymerases encoding RNA, was synthesized using a DNA-synthesator. The above modified oligo effectively suppressed the influenza A/PR8/34 virus reproduction and inhibited synthesis of the virus specific proteins in MDCK cells. The non-modified antisense oligo and the modified nonsense oligo did not affect the virus development under the same conditions. PMID- 1877398 TI - Properties of purine and pyrimidine analogs. PMID- 1877399 TI - Regulation of de novo and salvage pathways in chemotherapy. AB - An overview was presented of our approach of inhibition of de novo and salvage pathways in pyrimidine and purine metabolism. 1. Combination of acivicin, an inhibitor of de novo biosynthesis, and dipyridamole, a transport inhibitor, provided synergistic cytotoxicity in hepatoma and colon carcinoma cells. 2. AZT, a competitive inhibitor of the salvage enzyme, thymidine kinase, and 5-FU or MTX provided synergistic cytotoxicity in hepatoma 3924A. In human colon carcinoma HT 29 cells AZT and methotrexate yielded synergistic cytotoxicity and thymidine and hypoxanthine together provided protection from the action of these drugs. 3. These observations are significant because in rat hepatoma 3924A and in human cell lines HT-29, HL-60 and K562 thymidine kinase activity was 16- to 67-fold higher than that of dTMP synthase. Therefore, inhibition of dTMP synthase activity alone may provide poor responses because the salvage pathways can circumvent this block. 4. In leukemic patients treated with tiazofurin, an inhibitor of IMP dehydrogenase, the rate-limiting enzyme of GTP biosynthesis, and with allopurinol, which inhibits GPRT activity through raising plasma hypoxanthine levels, synergistic therapeutic results were obtained. The responses in sensitive patients entailed a decrease in IMP dehydrogenase activity and GTP concentration in leukemic cells and down-regulation of the ras and myc oncogenes. The down-regulation of the ras oncogene by tiazofurin through the decrease of GTP concentration has now been shown in K562, HL-60 and hepatoma cells and in patients with chronic granulocytic leukemia in blast crisis. Tiazofurin may be useful in studies on selective depression of the expression of the ras oncogene. 5. In 27 consecutive patients 50% responded positively to tiazofurin treatment. From this group, 10 out of 12 patients (83%) with chronic granulocytic leukemia in blast crisis responded to tiazofurin treatment. PMID- 1877401 TI - [Optic disc and glaucoma]. PMID- 1877400 TI - Studies on the mechanisms of inhibition of L1210 cell growth by 3,4 dihydroxybenzohydroxamic acid and 3,4-dihydroxybenzamidoxime. AB - Didox and Amidox inhibit L1210 cell growth in culture. At least one of the mechanisms in the mode(s) of action of the compounds is directed at the ribonucleotide reductase site. Partially purified preparations of ribonucleotide reductase activity are inhibited by Amidox and Didox. The formation of deoxycytidine nucleotides from [14C]cytidine in intact L1210 cells is also blocked. Didox and Amidox cause the decrease in the intracellular pools of the four dNTPs. Hydroxyurea-resistant L1210 cells are not cross-resistant to either Didox or Amidox. These data suggest that Didox and Amidox are not inhibiting ribonucleotide reductase through a mechanism similar to hydroxyurea. PMID- 1877402 TI - [Extracellular matrix of the optic nerve lamina cribrosa in monkey eyes with experimentally induced glaucoma]. AB - The changes of immunoreactivity and immunolocalization of the extracellular matrices (ECM), collagen type I through VI, laminin, fibronectin and alpha elastin, of optic nerve lamina cribrosa in argon laser induced glaucoma in monkey eyes were examined using a immunohistochemical method, biotin-streptavidin system. The results were consistent with the previous findings that in the experimental glaucoma eyes, diffuse immunoreactivity of collagen type I, III, V, VI, fibronectin were detected in the thickened and irregular laminar beams, while linear staining for collagen type IV and laminin were seen around the laminar beams and vascular walls were densely, thickly and irregularly, and furthermore immunoreactivity for alpha-elastin was reduced markedly in the glial columns and moderately in the lamina cribrosa. In the lamina cribrosa with optic disc cupping in laser-induced monkey glaucoma, the immunoreactivity for alpha-elastin was changed most greatly, and no qualitative differences were detected in comparison with normal fellow eyes for the other ECM components. PMID- 1877403 TI - [The distribution and characterization of sulfated-proteoglycans in the normal human lamina cribrosa]. AB - The distribution and morphological characterization of the sulfated-proteoglycans in the normal human lamina cribrosa under the electron microscope after staining with cationic-dye (Cuprolinic-Blue) in critical electrolyte condition were studied. Three types of Cuprolinic-Blue positive filaments were identified associated with collagen in the lamina cribrosa according to their size, electro density and their relation to the collagen fibrils. The thin and short Cuprolinic Blue positive filaments (referred to as CB-1 filament in this communication) distributed over the collagen fibers in relatively regular fashion. The intermediate-sized Cuprolinic-Blue positive filaments (CB-2) were seen randomly associated with collagen fibers. The clusters of large CB-3 filaments were seen unevenly associated with loosely packed collagen fibers. The higher electron density of CB-2 and CB-3 filaments than those of CB-1 filaments were also demonstrated. Cuprolinic-Blue positive dots and blots as well as various sizes of filaments could be identified in the basal lamina surrounding the collagen beams and in the basement membrane of the blood vessels. PMID- 1877404 TI - [Scanning electron microscopic observation of the collagen fibrillar network in Bruch's membrane by cell maceration]. AB - Cellular elements, including retinal pigment epithelia, were removed by the cell maceration method to obtain a three-dimensional view of the collagen fibrillar networks of Bruch's membrane. A bird's eye view of the inner collagenous zone of Bruch's membrane was obtained using the eyes of albino rabbits and Japanese monkeys. The eyes were treated with a low concentration of NaOH for several days and then observed with a scanning electron microscope. This procedure allowed the exposed inner collagenous zone of Bruch's membrane to be observed. In addition, the outer collagenous zone was also be observed in some of the specimens. Both zones were formed by dense lattices of fine collagen fibrils, and these fibrils frequently formed bundles in the outer collagenous zone. In the posterior poles of the eyes obtained from Japanese monkeys, a network of wavy fine collagen fibrils was observed. In both outer and inner collagenous zones, most of the collagen fibrils ran parallel to the retina. Fenestration of the sheet-like elastic layer was frequently observed through gaps in the thin collagen fibrillar network of the inner collagenous zone. The method employed in this study was considered suitable to obtain a wide bird's eye view of the collagenous zone of Bruch's membrane. PMID- 1877405 TI - [Three-dimensional observation of elastic tissue in Bruch's membrane by formic acid extraction]. AB - Japanese monkey and albino rabbit choroid were treated with hot-formic acid to remove the cellular elements and the extracellular matrices excluding the elastic tissues so that both three-dimensional and bird's eye views of the elastic layer of Bruch's membrane could be obtained. The only elastic layer was extracted and observed with a scanning electron microscope. Elastic layers were frequently extracted as translucent monolayered sheets with oval, sector-shaped fenestrations of varying sizes. Elastic fibers of 100-200nm in diameter crossed each other in these fenestrations. Other fine fibers connecting these elastic fibers and their sheet-like elastic plate were also observed. In Japanese monkey eyes, lattice structures formed by thick elastic fibers, 200-300nm in diameter, were conspicuous. This method proved suitable for the observation of the three dimensional structure of the elastic layer of Bruch's membrane. PMID- 1877406 TI - [Lectin binding in the interphotoreceptor matrix in neuraminidase-induced retinal detachment]. AB - Binding sites of fluorescence isocyanate-labeled lectins, peanut agglutinin (PNA) and Ricinus communis agglutinin-1 (RCA-1), were studied in the interphotoreceptor matrix (IPM) of adult rat retinas that were pretreated with an intravitreous injection of neuroaminidase. The localization of binding sites to the subretinal IPM differed significantly between the two lectins. PNA bound to the subretinal IPM components in a cord-like fashion that formed a bridge between the apical photoreceptor outer segments and the surface of the RPE. On the other hand, RCA-1 showed homogeneously prominent binding to the subretinal space IPM, the intensity of which appeared to inversely correlate with the extent of neuraminidase-induced retinal separation. The results suggest that the IPM may consist of mucin-type glycoconjugates as recognized by PNA and serum-type ones as bound by RCA-1, and that these IPM components may play different roles in the maintenance and organization of photoreceptor-RPE complex, e.g. the mucin-type for the retinal adhesion and the serum-type for the transport of metabolites. PMID- 1877407 TI - [A comparative study of optic disc appearances in progressive and non-progressive low-tension glaucoma]. AB - The relation between the optic disc appearances and the progression of visual field defects was studied by retrospective case review of 148 eyes of 74 patients with a diagnosis of low-tension glaucoma (LTG). Visual fields were tested by a Goldmann perimeter and the subjects were divided into two groups, i.e. 43 eyes (29.1%) with progression and 105 eyes (70.9%) without progression, according to Esterman's scale. In the group which showed progression, mean IOP (p less than 0.05), level of change in IOP and maximum of IOP (p less than 0.01) were significantly higher. No differences were observed in any of the following parameters: prevalence of peripapillary hemorrhage or crescent, rim pallor, disc/arteriole ratio, number of rim-crossing vessels. Mildly hypoplastic disc, however, was statistically more frequent in the progressive group (p less than 0.05). The authors suspect that not only IOP but some inherent factors concerning the optic nerve head may play an important role in the progression of LTG. PMID- 1877408 TI - [Reproducibility of three-dimensional point by point measurements on the optic nerve head surface using a computerized image analysis system]. AB - The reproducibility of topographic measurements of the optic nerve head was studied using a prototype Humphrey Retinal Analyzer system (Allergan Humphrey SKB, San Leandro, CA). Digital simultaneous stereographic images were obtained using programs in the Analyzer. The analyzer expressed the results in terms of microns of elevation at approximately 300 locations on the optic nerve head surface. At least 3 separate stereoscopic digital images were made of each of 8 eyes of 5 subjects. One randomly selected image of each disc was analyzed twice in order to determine intra-image reproducibility, and topographic analyses of two randomly selected images of each disc were compared to estimate the inter image variability. We calculated the coefficients of variation (CV) of measurements at the center point of the optic disc. Further, we computed the absolute value of the difference in the degree of elevation among the measured locations on the optic disc and calculated the median and 95 percentile value of that group of approximately 300 differences. The CV, medians, and the 95 percentile values thus obtained for the 8 discs ranged from 0 to 6.1%, from 6 to 20 microns, and from 20 to 69 microns, respectively for intra-image reproducibility. Those for inter-image reproducibility ranged from 1.5 to 59.1%, from 6 to 33 microns, and from 36 to 92 microns, respectively. PMID- 1877409 TI - [Color vision defects of macular diseases]. AB - Patients with macular diseases such as x-linked juvenile retinoschisis, cone dystrophy, and age-related macular degeneration were studied regarding color vision defects. In 9 of 15 eyes of patients with x-linked juvenile retinoschisis, blue-yellow defects were demonstrated. In the older patients with this dystrophy, color vision defects were more severe than in younger ones. Fluorescein angiography revealed retinal pigment epithelium (RPE) atrophy at the macular area in these older patients. Therefore, it was suggested that the color vision defects were due to dysfunction of the outer sensory retina, occurring secondarily to the inner sensory retina. In patients with cone dystrophy, all the examined eyes showed severe color vision defects. It was proved that the size of the atrophic lesion which when ophthalmoscopically evaluated was found to have some relationship with the degree of color vision defects. In patients with age related macular degeneration, most of the examined eyes showed color vision defects. Moreover eyes with soft drusen formation and/or RPE detachment usually showed more severe color vision defects than the eyes with hard drusen formation and/or RPE atrophy. PMID- 1877410 TI - [The investigation of the stereoacuity in infants measured by the TV-Random Dot Stereo Test]. AB - Evaluation of the level of stereoacuity in infants as early as possible is very important to detecting abnormalities and preventing further disturbance in visual functions. We developed a new instrument which permits the quantitative measurement of stereoacuity in infants. A total of 217 ophthalmologically normal infants were tested and stereoacuity was detected in 141 infants. Stereopsis is likely to arise at 3-4 months of age and develops as the infant grows. It can develop rapidly after the age of one year. The rate of detection was 48% in infants below 6 months old, and 65% as an overall mean among all age groups under 3 years of age. This new instrument, the TV-Random Dot Stereo Test, is very important to quantitatively measure stereoacuity of infants aged under 3 years, more simply and with greater reliability than other kinds of stereo tests for infants. PMID- 1877411 TI - [Endophthalmitis in Japan--a nationwide study with reference to type and etiology]. AB - A nationwide clinical study on bacterial and fungal endophthalmitis was done with special reference to their type and etiology. Two hundred and eighty cases of endophthalmitis were reviewed. All cases were divided into two categories such as exogenous (trauma, surgery, and ulcer) and endogenous (metastasis). Penetrating trauma was responsible for 93 cases (33.2%), surgery for 88 cases (31.4%), ulcer for 11 cases (3.9%) and metastasis for 88 cases (31.4%). Out of the 280 cases, 79 cases (28.2%) were microbiologically diagnosed through aqueous or vitreous tap or biopsy. The total numbers of isolated organisms amounted to 87 consisting of 43 Gram-positive bacteria, 30 Gram-negative bacteria and 14 fungi. The positive isolation was 31 out of 86 (36%) from the aqueous and 52 out of 103 (50%) from the vitreous. Exogenous types associated with trauma, surgery or ulcer were mainly caused by Gram-positive bacteria of 37 strains, led by coagulase-negative staphylococci in 14 cases. On the other hand, endogenous cases were mainly due to Gram-negative bacteria of 14 strains including Klebsiella pneumoniae in 5 cases, E. coli in 4 cases and fungi of 11 strains including candida spp in 9 cases. PMID- 1877412 TI - [Clinical evaluation of modifications of the SRK formula]. AB - It was previously reported that the axial length and the refractive error were analyzed in selecting intraocular lens powers which were calculated by the SRK formula. Moreover, the predicted postoperative refraction was compared with the actual postoperative refraction. Two modifications of the SRK formula were derived from these relationships as follows; Modified SRK formula 1: R = 0.98 (P I)-0.16L + 4.48, Modified SRK formula 2: R = 0.82 (P-I)-0.21L + 5.39. The modifications of the SRK formula were evaluated in 200 other eyes after posterior chamber lens implantation. As a result, the average refractive error was + 0.397 +/- 0.585D by the standard SRK formula, but it decreased by an average numbers of + 0.037 +/- 0.557D and + 0.047 +/- 0.547D respectively by modified SRK formulae 1 and 2. While the incidence of deviation within +/- 1.0D was 87.0% for the standard SRK formula, it was 94. 5% for both modified SRK formulas. The refractive errors, moreover, were less dependent on the axial length with both modified SRK formulae. The predicted postoperative refraction was more accurate by modified SRK formulae, especially between emmetropia and myopia up to 0.5 diopters. PMID- 1877413 TI - [A case of lacrimal gland malignant lymphoma, associated with Sjogren's syndrome]. AB - A 64 year-old female complained of left upper lid swelling. Painless mass lesions were found in her bilateral lacrimal gland areas. She also complained of a dry sensation in both eyes and her mouth. The rose bengal test, Schirmer's test and fluorescein dye test were positive. Lip biopsy revealed chronic sialoadenitis and rheumatoid factor titer was elevated. Anti-nuclear and anti-RNP antibodies were positive. Anti-SS-A and anti-SS-B antibodies were both negative. Left pre-and post auricular, cervical and inguinal lymph nodes were palpable. Excisional biopsies of bilateral orbital lesions and an inguinal lymph node revealed the presence of reactive lymphoid hyperplasia in the right orbit, and B cell type, diffuse, large cell lymphoma, in the left orbit and inguinal lymph node. Intensive chemotherapy resulted in complete remission. Lacrimal gland lymphoma must be considered when examining cases of Sjogren's syndrome. PMID- 1877415 TI - Is organized medicine dying? PMID- 1877414 TI - [A case of central retinal vein occlusion accompanied by central retinal artery occlusion]. AB - A 81-year-old woman developed central retinal vein occlusion (CRVO) in her left eye subsequent to central retinal artery occlusion (CRAO). She noticed sudden visual loss in the left eye. At initial examination, her left visual acuity was 0.03, and only a small visual field was preserved at temporal area. The left fundus showed findings of mild non-ischemic CRVO. In addition white clouded retina was recognized at the left posterior pole which indicated CRAO. FAG showed remarkably prolonged arterial circulation, but no retinal capillary obliteration. Then retinal hemorrhage increased rapidly and her left eye developed hemorrhagic retinopathy. Two weeks after initial examination, FAG showed extensive retinal capillary obliteration. In this case it was supposed that central retinal artery occlusion due to arteriosclerosis produced ischemic capillaropathy and venous thrombosis, after which restoration of arterial circulation caused hemorrhagic retinopathy. PMID- 1877416 TI - Staphylococcus aureus endocarditis in community hospitals. AB - We compared 13 cases of Staphylococcus aureus endocarditis from community hospitals to previous series all of which originated from university or tertiary care hospitals. In our experience Staph. aureus was the third leading cause of endocarditis and accounted for 20% of cases. The infection presented as one of three syndromes: native valve endocarditis, prosthetic valve endocarditis and endocarditis in drug addicts. Laboratory data revealed leukocytosis; infiltrates, nodules, congestive heart failure and cardiomegaly were seen on chest x-ray; and echocardiography infrequently detected vegetations. Criteria which favored the diagnosis of endocarditis in staphylococcemic patients were: absence of a primary site of infection, community acquisition of infection, metastatic infectious sequelae and vegetations documented by echocardiography. Treatment requires prolonged intravenous administration of high dose bactericidal antimicrobial agents; commonly nafcillin or oxacillin combined for a variable period with gentamicin. The mortality rate in our series was 23% and complications occurred in 70% of cases. PMID- 1877417 TI - The FDA as an information source for family physicians. PMID- 1877418 TI - ACOG issues report on induction and augmentation of labor. PMID- 1877419 TI - Good news from Washington, D.C.: medical malpractice reform proposals. PMID- 1877420 TI - Senate adopts two amendments on HIV and health professionals. PMID- 1877421 TI - Medicare, geriatrics and the family physician. PMID- 1877422 TI - Storage of poliovirus vaccine. PMID- 1877423 TI - The meaning of basic health care. PMID- 1877424 TI - Front-line attack on STD epidemic. PMID- 1877425 TI - Esophageal foreign bodies. AB - An impacted esophageal foreign body is most often an urgent, rather than a life threatening, medical situation. Pharmacologic or mechanical methods can be used to relieve the impaction, depending on the patient, as well as the location and physical properties of the foreign body. Flexible fiberoptic esophagoscopy is the accepted standard of care for removal of an object that is not smooth, radiopaque, inert or recently impacted. Although controversial, balloon catheter extraction may be an acceptable alternative in selected cases of esophageal impaction. Intravenous glucagon is useful in relieving distal impaction. PMID- 1877426 TI - Testicular torsion: a surgical emergency. AB - Testicular torsion is caused by twisting of the spermatic cord, which results in compromised testicular blood flow. The degree of ischemic injury is determined by the severity of arterial compression and the interval between the onset of symptoms and surgical intervention. Torsion usually occurs at puberty, and an anatomic defect known as "bell-clapper" deformity is usually present. Typical symptoms include acute scrotal pain with associated nausea and vomiting. Up to one-half of patients report previous similar episodes. On examination, the testis is high-riding, tender, swollen and firm. Testicular scan or Doppler ultrasound examination can be helpful in distinguishing torsion from acute epididymitis. Prompt surgical treatment is indicated to reduce the torsion, and bilateral orchiopexy is performed to prevent recurrence. Exocrine function, as determined by semen analysis, is often abnormal after unilateral torsion. PMID- 1877427 TI - Office dermatologic testing: the Tzanck preparation. AB - Whether a vesicobullous disease is intraepidermal or subepidermal is often difficult to determine from the clinical examination. The Tzanck preparation can provide clues that aid in the diagnosis of a number of diseases. It is particularly helpful in confirming the diagnosis of herpes infection. This article outlines the materials and steps for performing this valuable test. PMID- 1877428 TI - Diagnosing rheumatoid arthritis: current criteria. AB - Rheumatoid arthritis is a chronic, systemic inflammatory connective tissue disorder with major effects on the articular system. Causative mechanisms remain unknown, and no specific diagnostic tests are available. Descriptive criteria form the basis of disease classification and diagnosis. Either the 1987 American College of Rheumatology criteria for classification of rheumatoid arthritis or the new rheumatoid arthritis classification tree may be used to diagnose and classify this disease. PMID- 1877429 TI - Idiopathic hemochromatosis. AB - Hemochromatosis is a rare disorder in which about four times the normal amount of iron is absorbed in the intestine, resulting in the accumulation of iron in the skin, liver, pancreas and heart. Radiographic features may include a small liver on plain abdominal films, increased hepatic density on computed tomographic imaging, and loss of liver signal on magnetic resonance imaging as a result of the strong paramagnetic effect of iron. Management includes phlebotomy and supportive treatment of damaged organs. PMID- 1877430 TI - Serious soft tissue infections of the head and neck. AB - The head and neck contain a number of spaces that can be invaded by organisms of the mouth or by spread of cervical osteomyelitis. Infection in these spaces may progress from superficial infection to cellulitis to the formation of an abscess requiring immediate drainage. Spread of infection between spaces depends on anatomic location. Most patients require hospitalization and intravenous antibiotic therapy. Because a deep space infection may be occult, a high index of suspicion is required for diagnosis. Early recognition is necessary to avoid tissue damage, bacteremia or airway compromise. The possibility of deep space infection should be considered in any patient who does not respond to the usual treatment of an abscessed tooth or tonsillitis. This type of infection also should be considered in a toxic patient who has a fever of unknown origin, with or without blood cultures that show anaerobic organisms. Computed tomography or magnetic resonance imaging is usually necessary to locate the infection and to detect suppuration that will be amenable to surgical exploration and drainage. PMID- 1877431 TI - Techniques for antepartum fetal surveillance. AB - Deciding when to intervene in a pregnancy can be a complicated problem. Several methods of antepartum fetal surveillance can be helpful in the assessment of fetal well-being. The nonstress test is an effective screening tool for fetal well-being. Newer techniques such as the biophysical profile, fetal vibroacoustic stimulation and Doppler velocimetry are also available. PMID- 1877432 TI - Alcoholism in women. AB - Women differ from men in their drinking patterns and in the biologic consequences of alcohol use. Women more often drink at home and conceal their drinking behavior. Because women have a higher percentage of body fat and a lower percentage of body water than men, the same amount of alcohol causes more severe toxic effects in women than in men. Heavy alcohol consumption in women is associated with gynecologic dysfunction and fetal alcohol syndrome. Depression, anxiety or other psychiatric illness is also common in women alcoholics. Family physicians should be alert to the subtle behaviors that suggest alcoholism and be familiar with the available community resources and treatment options. PMID- 1877433 TI - Treatment of diabetes in the elderly. AB - Diabetes mellitus is one of the most common medical problems in elderly patients. There is a strong rationale for therapy in most patients with diabetes, even those who are asymptomatic. Family physicians should be aware of several age associated differences in the management and treatment of diabetes in older patients. For elderly patients, dietary modifications may include an increase in the percentage of carbohydrates and a decrease in the percentage of fat. For obese patients, dietary therapy should also emphasize a decrease in overall calories. Oral hypoglycemic agents are generally used as the initial drug therapy. Insulin therapy should be instituted when oral agents fail to reduce the blood glucose level, when the blood glucose level is very high and in other special circumstances. A careful choice of medications for other common problems associated with diabetes, such as hypertension, hyperlipidemia and peripheral neuropathy, is also essential. PMID- 1877434 TI - Adenosine for paroxysmal supraventricular tachycardia. AB - Adenosine is the most recent drug approved for the treatment of paroxysmal supraventricular tachycardia. Its advantage is that it is just as effective as verapamil and is far less toxic. The lack of toxicity is due to the extremely short half-life (one to seven seconds). The mechanism of action of adenosine is different from that of other antiarrhythmic agents. For the specific purpose of ameliorating paroxysmal supraventricular tachycardia, adenosine appears to be an ideal antiarrhythmic drug. PMID- 1877435 TI - HIV can be transmitted from asymptomatic carriers. PMID- 1877436 TI - Frequency of late reversibility in stress-redistribution thallium-201 SPECT using an early reinjection protocol. AB - To assess the efficacy of an early thallium-201 reinjection protocol for reducing the need for late redistribution imaging, the frequency of thallium-201 late reversibility was prospectively assessed in 62 patients who had stress redistribution thallium-201 studies by single-photon emission computerized tomography (SPECT), and who received 1 mCi of thallium-201 reinjection immediately following stress tomographic acquisition. These patients also demonstrated greater than or equal to 2 segments with nonreversible defects at 4 hour imaging and underwent late (18-to 72-hour) redistribution imaging. When the criterion of late reversibility was defined as greater than or equal to 1 segment with a 4-hour nonreversible defect demonstrating late reversibility, late reversibility was present in 36 (58%) of the 62 patients and in 88 (24%) of 368 SPECT segments. When the criterion of greater than or equal to 2 segments was used, late reversibility was found in 21 (34%) of the 62 patients and in 73 (20%) of the 368 segments. Of the 21 patients who had greater than or equal to 2 late reversible segments, 12 (57%) exhibited late reversibility in greater than or equal to 3 segments. The frequency of detected reversible defects increased from 32% by 4-hour imaging to 48% by combined 4-hour and late imaging (p less than 0.0001). The patients who demonstrated late reversibility could not be distinguished from those who had only late nonreversible defects by analysis of the clinical, exercise, and electrocardiographic (ECG) variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877437 TI - Long-term angiographic follow-up after angioplasty of venous coronary bypass grafts. AB - From April 1981 to June 1987, 57 patients underwent venous coronary bypass graft percutaneous angioplasty and had a minimal follow-up of 18 months. The procedure was elective for 28 patients, urgent for 19, and was considered as an emergency for 10. A total of 64 grafts were dilated that had been bypassed 58 +/- 48 months previously (range 2 to 184 months); lesions were located on the aortic anastomosis in 12 grafts, on the body in 38, and on the coronary anastomosis in 14. Technical success was 95.3% (61 of 64) per lesion; clinical success was 84.4% (54 of 64) per lesion and 82.5% (47 of 57) per patient. Thrombotic complications with images of a lacunar defect occurred in 11 grafts (17.2%). Predictive factors for these complications were: age of grafts 38.5% for greater than 60 month grafts versus 2.6% for less than 60 month grafts (p less than 0.01); site of lesion, body lesion 28.9% versus anastomosis none (p less than 0.01); type of lesion, concentric and short 6% versus other 29% (p less than 0.05); and recent fibrinolysis in 66% versus 10.6% (p less than 0.05). Long-term follow-up is available in the 47 successful patients and the three limited non-Q wave myocardial infarction patients. Two patients died at 13 and 17 months. Long-term angiographic follow-up is available in 45 of 48 patients or 94%. At the end of the study, 35 of 57 (61.4%) venous bypass grafts in 32 patients (64%) were patent after one or more percutaneous transluminal angioplasties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877438 TI - A comparison of multilesion percutaneous transluminal coronary angioplasty in elderly patients (greater than 70 years) and younger subjects. AB - Results of multilesion percutaneous transluminal coronary angioplasty (PTCA) were compared in 210 elderly patients (70 to 92 years, [group I] and 210 younger patients (40 to 69 years, [group II]. The elderly patients included more women (43% versus 24%) and patients with unstable angina (73% versus 55%). PTCA was successful in 87% of lesions in group I and in 94% in group II (p less than 0.001). Only circumflex artery dilatation was less successful in group I (78% versus 91%, p less than 0.002). PTCA was successful in all lesions of at least one vessel in 89% of group I patients and in 94% of group II patients (p less than 0.06). Successful dilatation of all lesions was achieved in 77% of group I and in 85% of group II patients (p less than 0.05). Complication rates were similar for both groups. These data demonstrate a high rate of success and safety in elderly patients undergoing multilesion PTCA despite the presence of several risk factors (advanced age, female sex, unstable angina). The lower PTCA success rate in these patients compared with younger subjects is almost entirely attributable to reduced success for circumflex artery lesions. PMID- 1877439 TI - Inability of coronary blood flow reserve measurements to assess the efficacy of coronary angioplasty in the first 24 hours in unselected patients. AB - To determine functional and anatomic changes in the first 24 hours after coronary angioplasty, we studied at random 15 patients (9 men, mean age 60 years) who underwent coronary angioplasty of 16 coronary arteries. Quantitative coronary angiography and coronary flow reserve measurements from digitized coronary angiograms were performed before, immediately after, and 24 hours after coronary angioplasty. Calculated were the minimal luminal diameter, obstruction area, and percentage diameter stenosis from two preferably orthogonal projections. Prior myocardial infarction in the myocardial region of interest was present in four patients. Seven patients had multivessel disease. Collateral vessels supplying the compromised flow region were observed in three patients. Six patients had refractory unstable angina pectoris. After coronary angioplasty, angiographically visible dissection was noted in six patients, whereas side branch occlusion was observed in one. Minimal luminal diameter before, immediately after, and 24 hours after was 0.93 +/- 0.18 mm, 1.53 +/- 28 mm, and 1.53 +/- 0.21 mm, respectively; obstruction area was 0.70 +/- 0.26 mm2, 1.92 +/- 0.69 mm2, and 1.87 +/- 0.51 mm2, respectively; diameter stenosis was 60.4 +/- 8.0%, 36.8 +/- 11.4%, and 37.6 +/- 5.3%, respectively. The coronary flow reserve (lower limit of normal with this technique 3.4) was essentially the same before and immediately after coronary angioplasty (1.26 +/- 0.59 vs 1.30 +/- 0.42, p = NS) with a slight improvement to 1.78 +/- 0.90 (p less than 0.05) 1 day later. Coronary artery dimensions correlated poorly with coronary blood flow reserve before and after angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877440 TI - The coronary artery response to implantation of a balloon-expandable flexible stent in the aspirin- and non-aspirin-treated swine model. AB - Intracoronary stents may potentially alleviate some of the problems associated with coronary angioplasty. Since the anatomy and physiology of swine coronary arteries closely resemble those of humans, the response to implantation of the Glanturco-Roubin, balloon-expandable, flexible stent was studied in this model. Additionally, the effect of aspirin, 1 mg/kg/day orally, on this response was evaluated. Eighteen Hanford minature swine underwent stenting of the left anterior descending coronary artery. Two died within 24 hours of stent implantation. The 16 survivors were put to death at 4 (n = 4), 11 (n = 4), 28 (n = 4), 56 (n = 3), and 180 (n = 1) days. Angiographically, reduction of stent lumen diameter of 0.1 to 1.3 mm was observed and was maximum at 11 days, with gradual improvement at subsequent time periods. Scanning electron microscopy, transmission electron microscopy, and light microscopy showed early disruption of subjacent endothelium, and adherence of platelets to exposed subendothelium and stent wires. Microthrombi were readily apparent. At 11 days, intimal thickening, made up predominantly of smooth muscle cells with abundant extracellular matrix, was observed and covered the stent wires. At 28 days, regression of intimal thickening was apparent and a confluent endothelium with flow-directed orientation was seen. At 56 and 180 days, the luminal surface was smooth; intimal thickening averaged 525 microns over the stent wires and 55 microns away from the wires. Findings in aspirin-treated animals were similar to results in those that did not receive aspirin. Thus in this swine model, stent implantation results in a time-dependent and self-limited vascular response. PMID- 1877441 TI - Attenuation of circadian variation by combined antianginal therapy with suppression of morning and evening increases in transient myocardial ischemia. AB - The circadian variation of total ischemic activity was examined during 3289 hours of ambulatory ECG monitoring in 101 patients with stable angina pectoris and proved coronary artery disease, who were not receiving any prophylactic antianginal therapy. The 101 patients displayed 411 episodes of ischemia, 312 (76%) of which were silent; a circadian rhythm was noted for the occurrence of total and silent ischemia. Thirty-eight percent of the ischemic episodes occurred between 6 AM and 12 noon, and total and silent ischemia were significantly more frequent during this period compared with the other three 6-hour periods (p less than 0.01); a lesser peak was noted in the evening. The effects of metoprolol and combined therapy with metoprolol and nifedipine on the circadian variation of ischemic activity were studied in two subgroups of patients in a random, double blind study design (31 patients receiving metoprolol and 42 receiving combined therapy). During therapy with metoprolol the morning increase in ischemic activity was attenuated, and the highest frequency of ischemia was then noted in the evening (6 AM to 12 noon compared with 6 PM to 12 midnight; p less than 0.05). Combined therapy abolished the morning peak as did metoprolol monotherapy, but even the evening increase in ischemic activity was attenuated (p less than 0.05). The diurnal distribution of the mean heart rate at the onset of ischemia, when patients were off therapy, showed a morning increase similar to the increase in ischemic activity but no second peak in the evening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877442 TI - Transmural distribution of myocardial edema by NMR relaxometry following myocardial ischemia and reperfusion. AB - To determine the distribution and extent of myocardial edema resulting from ischemia and reperfusion, seven open-chest dogs underwent occlusion of the left circumflex coronary artery for 2 hours (group I), and 10 underwent occlusion for 2 hours and reperfusion for 2 hours (group II). Proton nuclear magnetic resonance spectroscopy (T1 and T2 relaxation times) and percent water content were determined to quantitate the amount of edema. There was a transmural increase of the T1 relaxation time of the central ischemic zone in groups I and II, although this increase was significantly greater in group II in both the subendocardium (group I = 707.8 +/- 12.5 msec, group II = 813.2 +/- 36.2 msec; p less than 0.01) and subepicardium (group I = 641.7 +/- 20.5 msec, group II = 760.5 +/- 34.7 msec; p less than 0.01). These increases were also observed in the T2 weighted relaxation time in the subendocardium (group I = 54.7 +/- 0.8 msec, group II = 78.7 +/- 6.3 msec; p less than 0.005) and subepicardium (group I = 54.0 +/- 1.4 msec, group II = 73.1 +/- 4.0 msec; p less than 0.001). Transmural differences were evident between the myocardial layers with increased T1 relaxation times (p less than 0.01) in the subendocardium in both groups. Similar increases were noted in the percent water content of the myocardium. Thus T1 and T2 relaxation times lengthened with an increase in myocardial water content following occlusion, and these relaxation times were augmented by reperfusion. We conclude that ischemia-induced edema occurs in a transmural distribution from subendocardium to subepicardium following occlusion, and this edema is further enhanced by reperfusion. PMID- 1877443 TI - Functional recovery of hibernating myocardium after coronary bypass surgery: does it coincide with improvement in perfusion? AB - To determine the relationship between functional recovery and improvement in perfusion after coronary artery bypass graft surgery (CABG), 49 patients were studied. Radionuclide angiography was performed before, 1 month after, and 6 to 12 months after CABG to evaluate regional wall motion. Exercise thallium-201 myocardial perfusion imaging was done before and 1 month after CABG to assess regional perfusion. Preoperative asynergy was observed in 108 segments, and 74 of them showed an improvement in wall motion 1 month after CABG (segment A). Sixty six of these segments (89%) were associated with an improvement in perfusion. Eight segments that had not improved 1 month after CABG demonstrated a delayed recovery of wall motion 6 to 12 months after CABG (segment B). However, seven of eight segments (88%) already showed an improvement in perfusion 1 month after CABG. A total of 82 segments exhibited functional recovery after CABG and were considered hibernating segments. In the preoperative study segment B more frequently had areas of akinesis or dyskinesis than segment A (75% vs 34%, p less than 0.05). The mean percent thallium-201 uptake in segment B was lower than that in segment A (74% +/- 9% vs 83% +/- 8%, p less than 0.05). Functional recovery of hibernating myocardium usually coincided with an improvement in perfusion. However, delayed functional recovery after reperfusion was observed in some instances. Severe asynergy and severe thallium-201 defects were more frequently observed in these segments with delayed recovery. Hibernating myocardium might remain stunned during those recovery periods. PMID- 1877444 TI - U74006F, a novel 21-aminosteroid, inhibits in vivo lipid peroxidation but fails to limit infarct size in a canine model of myocardial ischemia reperfusion. AB - Peroxidation of membrane lipids has been suggested to play a role in the pathogenesis of myocardial ischemia/reperfusion injury. We therefore assessed the efficacy of U74006F, a potent in vitro vitamin E-like inhibitor of lipid peroxidation, in limiting infarct size in a canine model of transient coronary artery occlusion. Twenty dogs underwent 2 hours of occlusion of the left anterior descending coronary artery and 6 hours of reperfusion. U74006F or saline solution was administered continuously from 1 hour of occlusion to the end of the experiment. U74006F blunted any increase in production of conjugated dienes (an index of lipid peroxidation) at both 30 minutes (1.73 +/- 0.16 mol/L x 10(-4) vs 2.62 +/- 0.22 in control dogs, p less than 0.05) and 6 hours (1.39 +/- 0.22 vs 2.06 +/- 0.18 in control dogs, p less than 0.05) after reperfusion. Furthermore, 6 hours after reflow vitamin E levels tended to be lower than baseline values in control dogs and higher than baseline values in dogs treated with U74006F. However, analysis of infarct size indicated no statistically significant difference between the two groups when expressed either as a percentage of the left ventricle (10.4 +/- 1.8% in U74006F vs 15.2 +/- 2.4% in control dogs) or as a percentage of the area at risk (33.0 +/- 5.5% in U74006F vs 37.8 +/- 4.5% in control dogs). Although U74006F appeared to be a potent in vivo inhibitor of lipid peroxidation, it failed to limit infarct size after 2 hours of occlusion and 6 hours of reperfusion in this canine model. PMID- 1877445 TI - Positive and negative exercise test results with and without exercise-induced angina in patients with one healed myocardial infarction: analysis of baseline variables and long-term prognosis. AB - The prognostic implications of exercise test results with and without exercised induced angina are not completely understood. In the Program On the Surgical Control Of the Hyperlipidemias (POSCH), 838 subjects with hyperlipidemia who had one healed myocardial infarction were studied and followed for 6 to 13 years (mean 8.6). Of the 417 control subjects, 279 had a treadmill exercise test result that was definitely positive or negative. Angina was also induced by exercise in 30% (45/150) and 8% (10/129) of those with a positive and a negative test result, respectively (p less than 0.0001). The data showed no difference between subjects with a positive or a negative test result with or without angina as regards levels of blood lipids, type of myocardial infarction (Q or non-Q wave), left ventricular function, or prognosis as defined by death, atherosclerotic coronary heart disease death, or myocardial infarction. PMID- 1877446 TI - Time course of creatine kinase release after termination of sustained ventricular dysrhythmias. AB - Differentiation between primary and secondary (caused by acute myocardial infarction) ventricular fibrillation has important therapeutic and prognostic implications. The diagnosis of myocardial infarction is based on clinical, ECG, and creatine kinase MB isoenzyme (MBCK) activity. Enzymatic criteria might not be able to confirm the diagnosis of myocardial infarction after recent cardioversion. The routine use of electrophysiologic studies involving the induction and termination of ventricular dysrhythmias provides a setting in which enzyme release as a result of cardioversion alone can be examined. Therefore a systematic investigation of the magnitude and time course of creatine kinase (CK) and MBCK release was performed after termination of ventricular dysrhythmias in 57 patients undergoing electrophysiologic studies. Of patients requiring external cardioversion, only 50% had an elevation in CK and MBCK activity. Elevation when present corrected with the number of shocks and cumulative energy delivered. The magnitude of MBCK release exceeded 10% of the total CK activity in 9% of observations. Pace-termination of ventricular tachycardia did not result in enzyme release. Arrhythmia characteristics, coronary artery disease, and left ventricular function did not affect the magnitude of the time course of enzyme release. These data suggest that cardioversion with multiple shocks may result in a component of MBCK release, and thus a false positive diagnosis of primary acute myocardial infarction may be made by relying exclusively on the enzyme release pattern. PMID- 1877447 TI - Effects of electrophysiologic testing of the automatic implantable cardioverter defibrillator on left ventricular systolic function and diastolic filling. AB - We investigated the effects of electrophysiologic testing of the automatic implantable cardioverter-defibrillator (AICD) on left ventricular systolic function and diastolic filling in 12 patients. Ventricular tachycardia or ventricular fibrillation was induced by programmed electrical stimulation and alternating-current, respectively. Patients were studied before and immediately after, 10 minutes after, and 1 hour after defibrillation by the AICD using M mode, two-dimensional, and pulsed Doppler echocardiography. Immediately after defibrillation, increases were found in the peak early filling velocity (70 +/- 10 cm/sec to 84 +/- 24 cm/sec, p less than 0.01), peak early-to-atrial filling velocity ratio (1.05 +/- 0.21 to 1.29 +/- 0.26, p less than 0.005), and maximum rate of diastolic chamber enlargement (82 +/- 26 mm/sec to 102 +/- 44 mm/sec, p less than 0.05). These changes were not evident at 10 minutes and 1 hour. Cardiac output and ejection fraction were unchanged after defibrillation. Heart rate and diastolic filling time were unchanged. We conclude that electrophysiologic testing of the AICD does not impair left ventricular function in the immediate to 1-hour period after defibrillation. Left ventricular systolic function is unchanged and diastolic filling is enhanced. PMID- 1877448 TI - Effects of long-term amiodarone therapy on the defibrillation threshold and the rate of shocks of the implantable cardioverter-defibrillator. AB - The effects of long-term amiodarone therapy on the defibrillation thresholds and the rate of shocks were evaluated in 62 patients who had implantation of an automatic cardioverter-defibrillator (n = 53) or prophylactic implantation of patch electrodes (n = 9) who were survivors of sudden cardiac death (n = 34) or had refractory rapid ventricular tachycardia (n = 28). There were 53 men and 9 women, with ages ranging from 18 to 76 years (mean +/- SD, 60 +/- 12). Coronary artery disease occurred in 50 patients (80.6%), cardiomyopathy occurred in six (9.7%), valvular heart disease developed in two (3.2%), primary electrical disease developed in two (3.2%), hypertensive heart disease materialized in one (1.6%), and Ebstein's anomaly occurred in one (1.6%). The left ventricular ejection fraction varied from 10% to 75% (mean, 37 +/- 17%). All patients had failed a mean of 3.9 +/- 1.6 antiarrhythmic drugs prior to implantation of the device. Twenty-eight patients (45%) were taking amiodarone up to the time of surgery, with a mean daily dose of 406 +/- 147 mg (range 200 to 800) and for a mean duration of 6.0 +/- 6.7 months (range 1 to 36 months). The mean defibrillation threshold (DFT) was 12.0 +/- 4.4 joules (range 5 to 20) in the group taking amiodarone and was not significantly different from that of the group not taking amiodarone (n = 32) (mean DFT 12.3 +/- 5.5 joules, range 5 to 30; p = 0.77).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877449 TI - Single- versus dual-chamber sensor-driven pacing: comparison of cardiac outputs. AB - Previous studies have shown that single-chamber sensor-driven pacing improves exercise tolerance for patients with chronotropic incompetence. However, long term single-chamber pacing has a number of inherent problems that limit its usefulness. Although sensor-driven dual-chamber pacing largely obviates the problems inherent with single-chamber sensor-driven pacing, the physiologic benefit of dual-chamber sensor-driven pacing has not yet been demonstrated. Accordingly, the purpose of this study was to compare exercise-induced cardiac output for patients with chronotropic incompetence, after programming their pacemakers to either a simulated sensor-driven single or simulated dual-chamber mode. Cardiac output was measured noninvasively at rest and peak exercise using standard Doppler-derived measurements, obtained in a blinded fashion. At rest the Doppler-derived resting VVI and DDD cardiac outputs were 4.49 +/- 0.3 L/min and 4.68 +/- 0.3 L/min, respectively. At peak exercise, the DDD cardiac output was 5.07 +/- 0.5 L/min, whereas the simulated activity VVI and DDD cardiac outputs were 6.33 +/- 0.6 L/min and 7.41 +/- 0.70 L/min, respectively. Analysis of variance showed that there was an overall significant difference in cardiac output from rest to peak exercise (p less than 0.001). However, only the simulated activity DDD cardiac output was significantly different from its respective control value (p less than 0.05). Thus this study shows for the first time that the addition of rate responsiveness to dual-chamber pacing results in a significant improvement in cardiac output for patients with chronotropic incompetence. PMID- 1877450 TI - Mixed venous oxygen saturation for differentiating stable from unstable tachycardias. AB - Current antitachycardia systems are incapable of adequately distinguishing stable from unstable tachycardias. Previously, integration of a pressure sensor or an impedance sensor, together with electrogram analysis, has been investigated as an improved method of identifying unstable arrhythmias. A mixed venous oxygen saturation sensor was investigated for differentiating stable from unstable paced and induced tachycardias in 10 patients. During rapid pacing at 600, 500, 400, 350, 300, and 250 msec cycle lengths, mixed venous oxygen saturation decreased as cycle length decreased. For any given cycle length, rapid ventricular pacing tended to result in greater mixed venous oxygen desaturation compared with atrial pacing. Mixed venous oxygen saturation decreased similarly during induced ventricular tachycardias at cycle lengths greater than 230 msec. However, ventricular tachycardias at cycle lengths less than or equal to 230 msec and ventricular fibrillation had no effect on mixed venous oxygen saturation until after termination. Subsequently, a mixed venous oxygen saturation-tiered therapy algorithm (cycle length less than or equal to 230 msec = unstable; cycle length greater than 230 msec and MVO2 greater than or equal to 6% over 30 seconds = unstable) was developed and was tested retrospectively in 113 paced and induced tachyarrhythmias in these 10 patients for detecting unstable tachycardias (defined as a decrease from baseline systolic arterial pressure of greater than or equal to 50 mm Hg at 15 seconds). The mixed venous oxygen algorithm had 93% sensitivity and 96% specificity compared with rate-only (rate greater than or equal to 170 beats/min) detection with 93% sensitivity and 71% specificity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877451 TI - Age-related changes in the clinical and electrophysiologic characteristics of patients with Wolff-Parkinson-White syndrome: comparative study between young and elderly patients. AB - The natural history of patients with Wolff-Parkinson-White (WPW) syndrome remains an intriguing question with respect to clinical decision-making, since serial electrophysiologic data spread over several decades in the same patient are not available in the literature. To study the age-related changes in WPW syndrome, we compared two separate groups of patients referred to this Medical Center for electrophysiologic studies because of a clinical presentation with significant arrhythmias. An elderly group of 42 patients aged 50 years or more were compared with a younger group of 51 patients aged 15 to 30 years. The groups were comparable in terms of clinical presentation, including the number of patients who had reported syncopal episodes and those requiring cardioversion of their tachyarrhythmias. Baseline electrophysiologic variables such as sinus rate; sinoatrial conduction time; corrected sinus node recovery time; AH interval; and effective refractory periods of the right atrium, atrioventricular (AV) node, and right ventricular muscle, were significantly greater in the elderly group. Similarly, the anterograde effective refractory period of the bypass tract, the shortest atrial pacing cycle length with 1:1 anterograde conduction via the bypass tract, retrograde effective refractory period of the bypass tract, the shortest ventricular pacing cycle length with 1:1 retrograde conduction via the bypass tract, the shortest consecutive preexcited R-R interval during atrial fibrillation, and the cycle length of orthodromic atrial ventricular reciprocating tachycardia were significantly greater in the elderly group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877452 TI - Abnormal responses to orthostatic testing in children and adolescents with recurrent unexplained syncope. AB - Syncope in the pediatric age group is a frequent event. Most often the cause is readily apparent--i.e., orthostatic hypotension or a vasovagal event. However, there are a large number of children with frequent recurrent unexplained syncope. Neither history, physical examination, nor standard testing reveals a cause. One hundred four consecutive patients were evaluated by orthostatic testing after standard methods found no cause for the recurrent syncope. Forty-seven (44%) of these 104 patients had syncope produced by orthostatic testing. Twenty-six of the 47 (55%) became syncopal within 5 minutes of testing initiation and 21 of the 47 (45%) after 5 to 11 minutes of testing. These patients had an average decrease of 81.5 mm Hg in blood pressure and a 25 beat/min decrease in heart rate. Of 12 control subjects, none lost consciousness with standing times as long as 14 minutes. Pacing was ineffective in preventing syncope, as two patients with a previously implanted normally functioning pacemaker had recurrent syncope clinically. Syncope was also induced by orthostatic testing, with the pacemaker showing a normal response with pacing as the patient became bradycardic. The syncopal event produced by orthostatic testing occurred with a downward blood pressure trend and a narrowing of the pulse pressure without a significant increase in heart rate. This was followed by a sudden drop in blood pressure and then by bradycardia. There is a group of children and adolescents with recurrent unexplained syncope due to abnormal orthostatic control mechanisms. Orthostatic testing appears helpful in identifying these patients. PMID- 1877453 TI - Dilated cardiomyopathy with mitral regurgitation: decreased survival despite a low frequency of left ventricular thrombus. AB - Ninety-one patients with dilated cardiomyopathy were studied by two-dimensional, pulsed, and color Doppler echocardiography (1) to detect and quantify mitral regurgitation (MR), (2) to record apical flow velocities in systole and diastole, and (3) to detect the presence of left ventricular thrombi. MR was detected in 57% of the patients and thrombi were present in 40%, but the occurrence of both MR and thrombus was rare (8%). Apical flow velocity was significantly higher throughout the cardiac cycle in the group with MR (diastole 15 +/- 7 vs 9 +/- 7 cm/sec; systole 29 +/- 12 vs 16 +/- 13 cm/sec; p less than 0.001 for both), accounting for the rarity of thrombi in this group. Follow-up data on 89% of the patients showed markedly decreased survival in the group with MR (22% vs 60% at 32 +/- 6 months, p less than 0.005), and this was evident even in patients with mild MR. Thus although MR is a noninvasively obtainable marker of a large subgroup of patients with dilated cardiomyopathy "protected" from left ventricular thrombus formation, it is a sensitive marker of decreased survival. PMID- 1877454 TI - Characteristics of serial electrocardiograms in heart transplant recipients. AB - To characterize "normal electrocardiogram patterns" after transplantation, serial surface 12-lead electrocardiograms (ECGs) taken 2 weeks, 1 month, and 1 year postoperatively in a group of 50 heart transplant recipients were analyzed and were correlated with clinical parameters. Some recipient atrial activity was evident in 40% of patients at 2 weeks, but in only 16% at 1 year; donor atrial activity was normal in 90% to 94% of patients at all times. ECG intervals generally were normal and did not change over time. The most prevalent abnormality was the presence of incomplete (IRBBB) or complete right bundle branch block (RBBB) patterns (14% at 2 weeks, 16% at 1 month, and 22% at 1 year). In patients with hemodynamic measurements available approximately at the time of the ECG recording 1 year following transplantation, there was a significant correlation between the presence of IRBBB and RBBB patterns and somewhat higher levels of right atrial mean pressure (6.8 versus 3.9 mm Hg, p = 0.01), pulmonary artery systolic pressure (32.5 versus 24.5 mm Hg, p = 0.001) and diastolic pressure (16.2 versus 11.2 mm Hg, p = 0.004), and right ventricular systolic pressure (31.4 versus 26.9 mm Hg, p = 0.019) and pulmonary artery wedge mean pressure (11.3 versus 7.9 mm Hg, p = 0.010). Repolarization changes were also common but decreased in frequency over time (78% at 2 weeks to 34% at 1 year) and did not correlate with the presence or absence of rejection. We conclude that ECG abnormalities in heart transplant recipients are generally mild and that IRBBB and RBBB patterns correlate with increased right heart pressures. PMID- 1877455 TI - Chagas' cardioneuropathy: effect of ganglioside treatment in chronic dysautonomic patients--a randomized, double-blind, parallel, placebo-controlled study. AB - To date, there is no effective pharmacologic treatment for Chagas' cardioneuropathy, one of the most common causes of congestive heart failure and sudden death in the world. Fifty-eight adults with positive serology for Chagas' disease and abnormal autonomic nervous system tests participated in this placebo controlled clinical trial with Cronassial (mixed gangliosides), 40 mg daily intramuscular injection for 4 or 8 weeks. We measured postural response (heart rate, systolic and diastolic arterial blood pressure changes in response to standing); heart rate changes induced by cough and hyperventilation reflex tests; dizziness on standing; number of stress-induced arrhythmias; and periodic acid Schiff (PAS)-positive T-lymphocyte percentage in blood samples. Cronassial is safe and significantly improves systolic blood pressure (p = 0.050) and double product responses to postural stress (p = 0.028), hyperventilation heart rate response (p = 0.007), frequency of dizziness episodes (p less than 0.001), number of arrhythmias (p = 0.033), and percentage of PAS-positive T-lymphocyte counts (p less than 0.001) compared with placebo. PMID- 1877457 TI - Altered myocardial high-energy phosphate metabolites in patients with dilated cardiomyopathy. AB - Myocardial high-energy phosphate metabolism in patients with dilated cardiomyopathy (DCM) of ischemic or idiopathic etiology was assessed at rest by one-dimensional phase-encoded 31P-nuclear magnetic resonance (NMR) spectroscopy studies performed in conjunction with 1H imaging in 20 patients with DCM and in 12 normal volunteers. The measured values of anterior myocardial phosphocreatine/beta-adenosine triphosphate (PCr/beta-ATP), corrected for partial saturation and contamination of the spectra by blood metabolites, averaged 1.80 +/- 0.06 (mean +/- SE) in normal volunteers and 1.46 +/- 0.07 in the patients overall, a highly significant (p less than 0.001) decrease. In patients with DCM accompanied by coronary artery disease (n = 9), the PCr/beta-ATP ratio averaged 1.53 +/- 0.07, while in those with DCM alone it was 1.41 +/- 0.12 (n = 11), a value that was not significantly different. There was no significant correlation (r = 0.34) between myocardial PCr/ATP ratio and left ventricular ejection fraction in patients. These studies demonstrate that myocardial PCr/ATP ratios are reduced at rest in human ischemic and idiopathic dilated cardiomyopathy. PMID- 1877456 TI - Angiotensin II and phorbol esters depress cardiac performance and decrease diastolic and systolic [Ca2+]i in isolated perfused rat hearts. AB - Both angiotensin II and the protein kinase C activator, phorbol 12-myristate 13 acetate (PMA), significantly depressed developed pressure, oxygen consumption, and coronary flow in isolated perfused rat hearts and caused a decrease in diastolic and systolic [Ca2+]i and [Ca2+]i transients. PMA and angiotensin II did not change the levels of cAMP but moderately decreased PCr/Cr. The decrease in systolic [Ca2+]i and amplitude of [Ca2+]i transients caused by PMA and angiotensin II resulted in depressed cardiac function. Hearts perfused with PMA and angiotensin II had a decreased sensitivity to extracellular calcium. Depressed developed pressure and oxygen consumption in the PMA- and angiotensin II-treated hearts may have been due to a decrease in amplitude of effective [Ca2+]i transients, because the [Ca2+]i threshold for cross-bridge interaction was presumably higher than the diastolic [Ca2+]i in these hearts. PMID- 1877458 TI - Tricuspid atresia: association with persistent truncus arteriosus. AB - Clinical, echo-Doppler, and pathologic data of a rare case of tricuspid atresia in association with truncus arteriosus are presented. There are only six patients (including the patient reported here) with this anomaly in whom detailed pathologic and/or clinical descriptions are available in the literature. An additional six cases were mentioned in the literature but without any details. A prevalence rate of 1.4% among tricuspid atresia cases is estimated. All infants presented with symptoms of cyanosis and/or congestive heart failure within a few days to 2 months after birth and died shortly thereafter. Cardiomegaly and increased pulmonary vascular markings on the chest x-ray film and left axis deviation with left ventricular hypertrophy on the ECG are usually present. Echocardiographic, catheterization, and angiocardiographic studies are helpful in documenting anatomic and physiologic features of this anomaly. Pathologically, the muscular type of tricuspid atresia, type I or II truncus arteriosus, a large subtruncal VSD, and a hypoplastic right ventricle are present. It is concluded that coexistence of tricuspid atresia and truncus arteriosus is rare; clinical, laboratory, and pathologic features are distinctive; the clinical presentation early in life with rapid demise is common; and prompt palliative surgery immediately after recognition of this anomaly should be undertaken. PMID- 1877459 TI - Comparative angiographic quantitative analysis of the immediate efficacy of coronary atherectomy with balloon angioplasty, stenting, and rotational ablation. AB - Interventional cardiology has branched in two directions: devices that primarily dilate coronary stenoses and those that debulk coronary tissue. Presently the optimum coronary intervention has not been found. While patients are awaiting randomized trials, a comparison based on matched quantitative coronary analysis may be useful to evaluate results of new interventional techniques. Therefore we compared 51 patients undergoing atherectomy with individually matched patients who were undergoing balloon angioplasty and stenting. The lesions were matched according to location of stenosis and reference diameter. Atherectomy and stenting resulted in larger gains in minimal luminal diameter compared with conventional balloon angioplasty. The minimal luminal diameter was increased from 1.2 +/- 0.4 mm to 2.6 +/- 0.4 mm in the atherectomy group and from 1.2 +/- 0.3 mm to 1.9 +/- 0.4 mm in the angioplasty group (p less than 0.00001). Atherectomy and stenting resulted in similar gains in minimum luminal diameter (1.4 mm vs 1.3 mm, p = NS). In addition, atherectomy and stenting appear to be more effective in resisting elastic recoil because of tissue removal and an intrinsic dilating effect, respectively. In matched populations directional atherectomy and stenting appear to be more effective intracoronary interventional devices than balloon angioplasty based on the immediate results. However, atherectomy is limited in smaller coronary vessels because of its larger size. PMID- 1877460 TI - Atrial antitachycardia pacing in children and young adults. AB - Atrial antitachycardia pacing was tested in 23 children and young adults. The majority of these patients had had operative repair of congenital cardiac defects and had both bradycardia and tachycardia. Pacemakers were usually implanted by the transvenous technique using bipolar leads. In each patient it was possible to find a tachycardia termination algorithm that successfully converted the tachycardia. In some patients very complex algorithms were necessary. In each patient it was also possible to find an algorithm that successfully differentiated the abnormal tachycardia from sinus tachycardia. Twelve patients required no antiarrhythmic drugs after pacemaker implantation, while 10 patients required one drug and one patient required two drugs. Eight of 23 patients had symptomatic tachycardias that required reprogramming the pacemaker to a different tachycardia termination sequence. Seven patients required reoperations, five for adapter problems and two for infection or erosion. Cardiac function improved in 15 of the 23 patients. Antitachycardia pacing is a viable option for management of tachycardias in children and young adults. PMID- 1877461 TI - Echocardiographic evidence that regional right ventricular dysfunction occurs frequently in anterior myocardial infarction. PMID- 1877462 TI - Focal basal perfusion defects: an unusual location of ischemia after coronary artery bypass grafting. PMID- 1877463 TI - Impending paradoxical embolism: echocardiographic diagnosis of an intracardiac thrombus crossing a patent foramen ovale. PMID- 1877464 TI - Echocardiographic detection of transient right heart thrombus: now you see it, now you don't. PMID- 1877465 TI - Cardiomyopathy with mitochondrial DNA mutations. PMID- 1877466 TI - Mitral regurgitation after ventricular tachycardia surgery. PMID- 1877468 TI - Preoperative detection of pericardial angiosarcoma by transesophageal echocardiography. PMID- 1877467 TI - Isolated partial anomalous pulmonary venous connection: echocardiographic diagnosis and a new color Doppler method to assess shunt volume. PMID- 1877469 TI - Prolapsing right atrial myxoma evaluated by transesophageal echocardiography. PMID- 1877470 TI - Cholesterol pericarditis causing cardiac tamponade. PMID- 1877471 TI - Percutaneous pericardial biopsy under echocardiographic guidance. PMID- 1877472 TI - Use of guiding catheters to target pericardial and endomyocardial biopsy sites. PMID- 1877473 TI - Is hypertension an insulin-resistant state? Metabolic changes associated with hypertension and antihypertensive therapy. AB - In this review, the relationship between hypertension and abnormal carbohydrate metabolism is explored. A review of the current literature reveals that people with hypertension are also likely to suffer from insulin resistance, glucose intolerance, and hyperinsulinemia. Likewise, hypertension is prevalent in obese and diabetic patients. Deficiency of insulin at the cellular level may be a common mechanism in the development of hypertension in patients with type I or type II diabetes mellitus. Essential hypertension appears to be an insulin resistant state. Insulin resistance may engender hypertension by increasing peripheral vascular resistance as well as by increasing salt retention at the level of the kidney. Therefore effective antihypertensive therapy should include agents that do not adversely affect carbohydrate metabolic abnormalities. Commonly used antihypertensive agents, such as thiazide, thiazide-like diuretics, and beta-blockers, are associated with glucose intolerance and increased insulin resistance. In contrast, angiotensin-converting enzyme inhibitors, calcium antagonists, and peripheral alpha-blockers (such as prazosin and terazosin) do not adversely affect glucose tolerance or insulin sensitivity. In addition, alpha blockers have a positive effect on the serum lipid profile. The entire multifactorial cardiac risk profile must be considered when choosing therapeutic agents for conditions that have an impact on cardiovascular disease. PMID- 1877474 TI - Comparison of chest pain, electrocardiographic changes and thallium-201 scintigraphy during varying exercise intensities in men with stable angina pectoris. AB - This study was performed to evaluate the presence of angina pectoris, electrocardiographic changes and reversible thallium-201 defects resulting from 2 different levels of exercise in 19 patients with known coronary artery disease and evidence of exercise-induced ischemia. The exercise protocols consisted of a symptom-limited incremental exercise test (Bruce protocol) followed within 3 to 14 days by a submaximal, steady-state exercise test performed at 70% of the maximal heart rate achieved during the Bruce protocol. The presence and time of onset of angina and electrocardiographic changes (greater than or equal to 0.1 mV ST-segment depression) as well as oxygen uptake, exercise duration and pressure rate product were recorded. Thallium-201 (2.5 to 3.0 mCi) was injected during the last minute of exercise during both protocols, and the images were analyzed using both computer-assisted quantitation and visual interpretations. Incremental exercise resulted in anginal symptoms in 84% of patients, and electrocardiographic changes and reversible thallium-201 defects in all patients. In contrast, submaximal exercise produced anginal symptoms in only 26% (p less than 0.01) and electrocardiographic changes in only 47% (p less than 0.05), but resulted in thallium-201 defects in 89% of patients (p = not significant). The locations of the thallium-201 defects, when present, were not different between the 2 exercise protocols. These findings confirm the sequence of the ischemic cascade using 2 levels of exercise and demonstrate that the cascade theory is applicable during varying ischemic intensities in the same patient. PMID- 1877475 TI - Usefulness of technetium-99m-MIBI and thallium-201 in tomographic imaging combined with high-dose dipyridamole and handgrip exercise for detecting coronary artery disease. AB - Forty-two patients with known stable coronary artery disease, referred for coronary angiography, were examined with technetium-99m-hexakis-2-methoxy-2 methylpropyl-isonitrile (MIBI) tomography combined with a high-dose dipyridamole infusion (0.7 mg/kg) and handgrip stress. MIBI tomography was unable to show coronary artery disease only in 2 patients, thus yielding a sensitivity figure of 95%. MIBI tomography correctly identified 27 (82%) of 33 stenotic lesions (greater than or equal to 50% diameter stenosis) of the left anterior descending artery, 17 (61%) of 28 of those of the left circumflex artery, and 28 (90%) of 31 of those of the right coronary artery. The overall vessel sensitivity was 78%. The computed lumen diameter stenoses were more advanced in cases detected than in those not detected with MIBI tomography: 87 +/- 14 vs 76 +/- 14% (p less than 0.01). The 50 to 69% stenoses did not show any tendency to produce less positive findings than those with greater than or equal to 70% stenoses. In the subgroup of 21 patients who also presented for thallium scintigraphy, the overall diseased vessel identification rate was 76% for thallium tomography and 83% for MIBI tomography (p = not significant). Minor noncardiac side effects related to the dipyridamole-handgrip test occurred only in 5% of 63 study sessions. A high-dose dipyridamole combined with isometric exercise is a safe stress method, and when used during scintigraphy, MIBI tomography is at least as efficient a tool as thallium tomography in detecting diseased vessel territories in patients in coronary artery disease. PMID- 1877476 TI - Comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Urochinasi per via Sistemica nell'Infarto Miocardico (USIM) Collaborative Group. AB - In a randomized trial of the effects on in-hospital mortality of intravenous urokinase plus heparin versus heparin alone, 2,531 patients with acute myocardial infarction in 89 coronary care units were enrolled for greater than 30 months. Patients admitted within 4 hours of the onset of pain were randomized to receive either intravenous urokinase (a bolus dose of 1 million U repeated after 60 minutes) plus heparin (a bolus dose of 10,000 U followed by 1,000 IU/hour for 48 hours) or heparin alone (infused at the same rate). Complete data were obtained in 2,201 patients (1,128 taking urokinase and 1,073 taking heparin). At 16 days, overall hospital mortality was 8% in the urokinase and 8.3% in the heparin group (p = not significant). Among patients with anterior infarction, mortality was 10.3% in the urokinase and 13.9% in the heparin group (p = 0.09; relative risk = 0.73). The incidence of major bleeding (urokinase 0.44%, heparin 0.37%) as well as the overall incidence of stroke (urokinase 0.35%, heparin 0.20%) was similar in the 2 groups. The rates of major in-hospital cardiac complications (reinfarction, postinfarction angina) were also similar. PMID- 1877477 TI - Prediction of major cardiac events after peripheral vascular surgery using dipyridamole echocardiography. AB - Patients undergoing peripheral vascular surgery are at increased risk of postoperative cardiac complications. To evaluate the role of dipyridamole echocardiography in predicting major cardiac events, 109 unselected patients undergoing elective peripheral vascular surgery were prospectively studied. Preoperative dipyridamole echocardiograms were interpreted by an echocardiographer unaware of all clinical data. Patients were followed up until hospital discharge by research physicians without knowledge of dipyridamole echocardiography results. Outcomes were classified using strict predefined criteria by reviewers unaware of other clinical and echocardiographic data. Of the 109 patients, 9 (8%) had positive studies defined as development of new regional wall motion abnormalities or worsening of preexistent wall motion abnormalities. Of these 9 patients, 7 had postoperative events, including 3 cardiac deaths, 1 nonfatal myocardial infarction, 2 with unstable angina, and 1 with pulmonary edema. Only 1 event occurred among the 100 patients with negative studies. The sensitivity and specificity of dipyridamole echocardiography for predicting cardiac events after vascular surgery were 88 and 98%, respectively; the positive and negative predictive values were 78 and 99%. The relative risk of having a cardiac event if dipyridamole echocardiography was abnormal was 78 (95% confidence interval, 11 to 564; p less than 0.0001). If these results are extended and confirmed by other investigators, preoperative dipyridamole echocardiography may be an important screening test for patients undergoing elective peripheral vascular surgery. PMID- 1877478 TI - Dispersion of ventricular repolarization in the long QT syndrome. AB - To identify markers of dispersion of the ventricular repolarization in the idiopathic long QT syndrome, body surface potential maps were analyzed in 40 such patients (mean age +/- standard deviation 21 +/- 11 years) and in 30 healthy control subjects (mean age 24 +/- 7 years). In each subject, 117 chest leads were recorded and maps of the integral values of the QRST interval were calculated. A multipolar distribution of the values, a marker of gross electrical inequalities of repolarization, was found only in 4 patients. To detect minor regional disparities of ventricular recovery, all the ST-T waveforms were analyzed in each subject. The ST-T waves were represented by a discrete series of potential values. The "similarity index" was computed by applying a principal component analysis, which represents (in percent) to what extent 1 fundamental pattern of ST-T reproduces all the recorded waveforms. The mean value of the similarity index was significantly lower in patients with long QT syndrome than in control subjects (49 +/- 10 vs 77 +/- 8%, p less than 0.0001). A value less than 61% (corresponding to 2 standard deviations below the mean value for controls) was found in 35 of 40 patients and in only 1 control subject (sensitivity 87%, specificity 96%). Thus, the similarity index is a more sensitive marker than the multipolar distribution of QRST integral maps in revealing electrical disparities of the ventricular recovery times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877479 TI - Dimensions of the human posterior septal space and coronary sinus. AB - Accurate anatomic localization of accessory pathways during preoperative electrophysiologic study and during operative mapping depends on a knowledge of the dimensions of the posterior septal space and the left free wall. These dimensions were therefore studied in 48 human cadaver hearts. Mean distance from the coronary sinus orifice to the left margin of the posterior septal space was 2.3 +/- 0.4 cm and mean length of the left free wall was 5.0 +/- 1.0 cm. The posterior septal space at the level of the valve anuli extended a mean of 3.4 +/- 0.5 cm around the epicardium. The width of the posterior septum measured in the coronary sinus was related to heart weight and a combination of body weight and patient age (p less than 0.05). The probability of an accessory pathway being located in the left free wall or the posterior septum during catheter mapping was calculated for various distances from the coronary sinus orifice for adults of different ages and body weights. In adults, accessory pathways located in the proximal 1.5 cm of the coronary sinus are almost always in the posterior septum. Those located between 1.5 and 3 cm from the coronary sinus orifice may be in either the left free wall or the posterior septum, and those located greater than 3 cm from the coronary sinus orifice are almost invariably in the left free wall. PMID- 1877480 TI - Stability over time of variables measuring heart rate variability in normal subjects. AB - Both time and frequency domain measures of heart rate (HR) variability have been used to assess autonomic tone in a variety of clinical conditions. Few studies in normal subjects have been performed to determine the stability of HR variability over time, or the correlation between and within time and frequency domain measures of HR variability. Fourteen normal subjects aged 20 to 55 years were studied with baseline and placebo 24-hour ambulatory electrocardiograms performed 3 to 65 days apart to assess the reproducibility of the following time domain measures of cycle length variability: the standard deviation of all normal cycle intervals; mean normal cycle interval; mean day normal cycle interval; night/day difference in mean normal cycle interval; root-mean-square successive cycle interval difference; percentage of differences between adjacent normal cycle length intervals that are greater than 50 ms computed over the entire 24-hour electrocardiographic recording (proportion of adjacent intervals greater than 50 ms); and the frequency domain measures of high (0.15 to 40 Hz), low (0.003 to 0.15) and total (0.003 to 0.40) power. The mean and standard deviations of these measures were virtually identical between placebo and baseline measurements and within the studied time range. Variables strongly dependent on vagal tone (high frequency, low-frequency and total power, root-mean-square successive difference, and percentage of differences between adjacent normal cycle intervals greater than 50 ms computed over the entire 24-hour electrocardiographic recording) were highly correlated (r greater than 0.8). It is concluded that measures of HR variability are stable over short periods of time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877481 TI - Comparison of allografts and prosthetic valves when used for emergency aortic valve replacement for active infective endocarditis. AB - Aortic valve replacement (AVR) using allografts is an established method of treating aortic valve disease. It is uncertain, however, whether the increased technical demands of allograft AVR can be justified in emergency operations. This study reports 15 patients treated between 1987 and 1990 for acute bacterial or fungal endocarditis involving the aortic valve. Patients underwent emergency AVR because of severe congestive failure, overwhelming sepsis or cerebral emboli. Eight patients received prosthetic valves (group I: 4 mechanical, 4 porcine) and 7 received human allografts (group II: 5 aortic and 2 pulmonary). The groups were comparable in age (group I, 55 years; group II, 51 years), intravenous drug abuse (group I, 1; group II, 3), and previous AVR (group I, 3; group II, 2). One group I and 4 group II patients had septal abscesses. Additional procedures in group I included mitral valve replacement (2), tricuspid valve replacement (1) and aortic root replacement (1). Additional procedures in group II were mitral valve repair (1), root replacement (1), atrial septal defect closure (1) and aortocoronary bypass (1). Mean bypass times (group I, 189 minutes; group II, 204 minutes) and cross-clamp times (group I; 108 minutes; group II, 121 minutes) were similar. Operative deaths occurred in 4 of 8 group I and 1 of 7 group II patients. All surviving patients have been successfully followed (group I, 28 months; group II, 18 months). No group I patient has required reoperation. One group II patients required reoperation for recurrent infection affecting the allograft, and another group II patient died 10 months postoperatively from noncardiac causes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877482 TI - Electrocardiographic correlates with left ventricular morphology in idiopathic dilated cardiomyopathy. AB - The purpose of the present study was to verify whether the electrocardiographic pattern of patients with idiopathic dilated cardiomyopathy (IDC) might be useful in predicting measurements of left ventricular (LV) morphology. A total of 12 electrocardiographic criteria for LV enlargement were evaluated in 67 patients with IDC, aged 14 to 68 years (mean 48), and were correlated to LV wall thickness, volume and mass, as assessed at angiography (all patients) and echocardiography (50 patients). Linear regression analysis showed weak correlations between multiple electrocardiographic criteria and LV wall thickness, volume and mass. Multiple logistic regression analysis showed that total 12-lead QRS amplitude, voltage criteria of Sokolow and Lyon, overshoot and U-wave inversion were the variables significantly related to LV wall thickness, as assessed by angiography (r = 0.55, p less than 0.005) and echocardiography (r = 0.43, p less than 0.025). The sum of T/R-wave ratios, the RV6/RV5 ratio and the Romhilt-Estes score were predictors of LV end-diastolic volume, as determined by angiography (r = 0.83, p less than 0.001) and echocardiography (r = 0.77, p less than 0.005). Total 12-lead QRS amplitude and the sum of T/R-wave ratios were the only independent predictors of LV mass, either angiographically (r = 0.81, p less than 0.001) or echocardiographically measured (r = 0.71, p less than 0.025). It is concluded that a single electrocardiographic criterion for prediction of LV morphology in patients with IDC is barely effective. Multiple electrocardiographic criteria should be utilized to better predict LV mass and distinguish reliably between LV wall thickening and dilatation. PMID- 1877483 TI - Factors influencing Doppler indexes of left ventricular filling in healthy persons. AB - Ninety-three healthy persons aged 11 to 91 years were studied to assess the factors influencing Doppler indexes of left ventricular (LV) diastolic filling. The effects of physical activity, alcohol consumption and smoking were tested in addition to those of age, sex, heart rate, body mass index, blood pressure, left atrial diameter, and LV end-diastolic diameter, wall thickness, mass and fractional shortening. The data were fitted stepwise into multiple linear regression models both in the total population and in 3 groups aged less than 40, 40 to 60 and greater than 60 years. In the total population, age explained 45 to 68% of the variation in the peak early and late diastolic velocities, their ratio, deceleration of the early velocity, atrial filling fraction and peak filling rate normalized to mitral stroke volume. With advancing age--and with increases in either body mass index, heart rate, diastolic blood pressure or LV mass--the indexes of early filling decreased, whereas with regular modest use of alcohol or regular aerobic exercise they increased (p less than 0.05 for all). In the middle-aged subjects, gender explained 32 to 57% of the variation in the peak atrial velocity, early to atrial peak velocity ratio and atrial filling fraction; the peak velocity ratio measured 1.4 +/- 0.3 (mean +/- standard deviation) in men vs 1.0 +/- 0.2 in women (p less than 0.001). In conclusion, many constitutional and physiologic factors and even life-style can influence the Doppler indexes of LV filling. This demonstrates the exquisite sensitivity of the method but indicates also that individual measurements must be interpreted with caution. PMID- 1877484 TI - Bivariate genetic analysis of left ventricular mass and weight in pubertal twins (the Medical College of Virginia twin study). AB - Left ventricular (LV) hypertrophy in adults is a recognized risk factor for the subsequent development of cardiovascular morbidity. To make informed preventive health decisions it is important to understand the interaction of genes and environment on LV mass. In both children and adults, weight is a strong correlate of LV mass. We hypothesized that genetic influences common to both of these variables could in part explain the strong relation between weight and LV mass in children. In a population of 341 twins (11 years old), these questions were asked: (1) How much of the total variance of LV mass is under genetic control? (2) After accounting for weight and weight adjusted for sexual maturity, how much of the remaining variance is genetic? (3) Of the total genetic variance, what proportion is specific for LV mass and what proportion is common to both weight and LV mass? (4) How much of the correlation between these 2 variables is explained by genes common to both LV mass and weight? Univariate genetic analyses documented that genes operating at different magnitudes in boys (63%) and girls (71%) explain a significant proportion of the variance of LV mass. After removing the effect of weight and sexual maturity by regression methods, genes remain an important influence. Bivariate genetic analyses confirmed that genes common to LV mass and weight significantly influence the covariation of these variables and that greater than 90% of the correlation of LV mass and weight is due to common genes. PMID- 1877485 TI - Left ventricular ejection fraction measured with Doppler color flow mapping techniques. AB - To determine if left ventricular (LV) ejection fraction (EF) can be accurately measured from the color Doppler examination, 11 patients (aged 0.4 to 22 years) underwent 2-dimensional and color Doppler examinations within 24 hours of cardiac catheterization. With use of a biplane Simpson's rule, LV end-diastolic volume, end-systolic volume and EF were measured from cineangiograms, 2-dimensional echocardiograms and color Doppler examinations. The 2-dimensional echocardiographic and color Doppler measurements were obtained from apical 4 chamber and long-axis views. The color Doppler examinations were performed by placing the color sector over the left ventricle only. The velocity scale was set at the lowest possible Nyquist limit (less than 0.17 m/s), and the highest possible carrier frequency was used to obtain this limit. With these settings, all flow signals in the LV chamber were aliased so that the entire chamber was filled with mosaic color Doppler signals. Motion of the surrounding LV walls gave rise to nonaliased (pure red-blue) signals. With use of an off-line analysis system equipped with a color frame grabber, the border of the mosaic color flow area was traced to obtain volumes and EF. End-diastolic and end-systolic volumes measured with color Doppler correlated well with those measured from 2 dimensional echocardiography (r = 0.99, standard error of the estimate [SEE] = 11.9 ml; r = 0.99, SEE = 4.4 ml, respectively) and cineangiography (r = 0.92, SEE = 16.8 ml; r = 0.90, SEE = 9.9 ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877486 TI - Dipyridamole sesta MIBI myocardial imaging. PMID- 1877487 TI - Anatomy of the "posterior septal space". PMID- 1877488 TI - Usefulness of serum creatinine as a marker for coronary events in elderly patients with either systemic hypertension or diabetes mellitus. PMID- 1877489 TI - Usefulness of placement of intraoperative epicardial wires during automatic implantable cardioverter-defibrillator insertion to preclude the need for transvenous catheters at the predischarge electrophysiology study. PMID- 1877490 TI - Electrophysiologic effects of intravenous propafenone at rest, during isoproterenol infusion and during exercise in the Wolff-Parkinson-White syndrome. PMID- 1877491 TI - Urinary kallikrein excretion in congestive heart failure. PMID- 1877492 TI - Comparison of mitral valve area results of balloon mitral valvotomy using the Inoue and double balloon techniques. PMID- 1877493 TI - Transesophageal echocardiographic features of stenotic bioprosthetic valves in the mitral and tricuspid valve positions. PMID- 1877494 TI - Diagnosis of patent ductus arteriosus in adults by biplane transesophageal color Doppler flow mapping. PMID- 1877495 TI - Echo-Doppler study of right ventricular filling in asymptomatic patients with Senning operation for transposition of the great arteries. PMID- 1877496 TI - Incidence and significance of a "step-down" in oxygen saturation from superior vena cava to pulmonary artery. PMID- 1877498 TI - Medical demobilization in wartime Russia, 1917 to 1918. PMID- 1877497 TI - Mitral and pulmonary venous flow under influence of positive end-expiratory pressure ventilation analyzed by transesophageal pulsed Doppler echocardiography. PMID- 1877499 TI - Benjamin Franklin's Poor Richard's Almanack and its maxims on physicians, medicine and nutrition. PMID- 1877500 TI - A major error in nomograms for estimating body mass index. AB - The Surgeon General's Report on Nutrition and Health and Diet and Health include a nomogram for determining body mass index (BMI, in kg/m2) when the subject's weight and height are known. I regret to report that the BMI in nomograms in these books are highly inaccurate when compared with direct calculations of BMI. Anyone wishing to use a nomogram for the rapid estimation of BMI should be cautioned against relying on the versions that appear in these books. PMID- 1877501 TI - The nature and individuality of within-subject variation in energy intake. AB - Examinations of observed within-subject variation in the energy intake of 29 adults participating in the Beltsville One-Year Dietary Intake Study suggest that individuals possess characteristic patterns of variability in total food intake (expressed as energy intake). Although the day-to-day variation appears to contain a sizable random component, significant nonrandom components were detected in the observed variation of all but one subject. Up to 37% of the total variance observed for a subject could be explained by the long- and short-term patterns identified in food intake. Both the shape and the amplitude of these patterns were unique to the individual subject, suggesting that observed within subject variance is a function of the particular combination of environmental and biological pressures on the individual's total food intake at any one time and of the methodological errors inherent in the estimation of this intake. PMID- 1877502 TI - Estimation of deep abdominal adipose-tissue accumulation from simple anthropometric measurements in men. AB - Equations have been developed for the prediction of deep abdominal adipose-tissue (AT) accumulation from anthropometric measurements in a sample of 110 men. An equation including the waist circumference and age could predict 74% of the variance in the amount of deep abdominal AT with an SEE of 29.6 cm2 (29.2% of the mean deep abdominal AT value), whereas another equation including the sagittal diameter, the waist-to-hip ratio (WHR), and age explained 76.6% of its variance with an SEE of 28.1 cm2 (27.7%). Equations excluding age as an independent variable were also developed. These results indicate that equations in which simple anthropometric measurements are used can provide further information in the assessment of the risk of cardiovascular disease in men. However, we must remember that our ability to predict the amount of deep abdominal AT from anthropometry is limited. PMID- 1877503 TI - Dietary intake and biochemical indices of nutritional status in an elderly population, with estimates of the precision of the 7-d food record. AB - Nutritional status was assessed in 82 healthy, free-living elderly subjects aged 65-89 y through anthropometric measurements, a 7-d dietary record, and selected serum indicators. The percentage of elderly subjects reporting intakes below two thirds of recommended intakes was highest for folate, vitamin D, calcium, magnesium, and zinc and varied from 23% to 72%. Of the nutritional indicators only serum zinc concentrations were deficient. The 7-d food record accurately classified individuals by usual or habitual intake for all nutrients except cholesterol. Dietary predictors of nutritional status were explored by using multiple regression. Iron status was predicted by protein and vitamin C intake and protein status, by dietary zinc. Serum concentrations of folate, vitamin C, and zinc were positively correlated to the dietary intake of the respective nutrients. The 7-d record was sufficiently precise to describe the intake of this healthy elderly population and to demonstrate evidence of clear relationships of dietary intake to serum nutritional indicators. PMID- 1877504 TI - Intracellular potassium and membrane potential in rat muscles during malnutrition and subsequent refeeding. AB - Nutrition alters total body potassium (TBK) and muscle potassium but little is known about in vivo intracellular K+. We measured free intracellular potassium ion activity (aKi+), membrane potential (Em), and total potassium (Kt) and calculated intracellular potassium concentration [K+]i in predominantly slow- (soleus) and fast- (extensor digitorum longus) twitch muscles in rats undergoing underfeeding and subsequent refeeding. After underfeeding, aKi+ and Em decreased (P less than 0.025 and P less than 0.006, respectively) only in soleus muscle with restoration after refeeding, whereas [K+]i decreased in both muscles (P less than 0.005) and remained low after refeeding. K+ supplementation did not significantly change these indices or the ratio of free to total intracellular potassium (gamma Ki+). The data show that aKi+ behaves differently from [K+]i during malnutrition and that changes in aKi+ occur especially in slow-twitch fibers, suggesting that previously observed changes in TBK and muscle function are the result of fundamental alterations in muscle-cell energetics and membrane functions, not just mass. PMID- 1877505 TI - Dietary energy requirements of young adult men, determined by using the doubly labeled water method. AB - We examined the hypothesis that current recommendations on dietary energy requirements may underestimate the total energy needs of young adult men, by measuring total energy expenditure (TEE) and resting energy expenditure (REE) in 14 weight-maintaining healthy subjects leading unrestricted lives. TEE and body composition were measured by using 2H(2)18O, and REE was measured by using indirect calorimetry. All subjects had sedentary full-time occupations and participated in strenuous leisure activities for 34 +/- 6 (SE) min/d. TEE and REE were 14.61 +/- 0.76 and 7.39 +/- 0.26 MJ/d, respectively, and 202 +/- 2 and 122 +/- 2 kJ.kg-1.d-1. There were significant relationships between TEE and both body fat-free mass (r = 0.732, P less than 0.005) and measured REE (r = 0.568, P less than 0.05). Measured TEE:REE values were significantly higher than the recommended energy requirement (1.98 +/- 0.09, compared with 1.55 or 1.67, P less than 0.005). These results are consistent with the suggestion that the current recommended energy intake for young adult men may underestimate total energy needs. PMID- 1877506 TI - Energy requirements of a postobese man reporting a low energy intake at weight maintenance. AB - Three experiments were performed to test the validity of the low reported energy intake of weight maintenance in a postobese man. In the first experiment the subject reported a mean energy intake of 8008 kJ/d during 16 d and he maintained a stable body weight. This finding was not reproduced in the second experiment, which consisted of a 6-d inpatient study during which the subject was confined to a whole-body calorimeter for 5 d. Indeed, he lost weight when fed a controlled energy intake of 7950 kJ/d. Moreover, this experiment showed that direct and indirect calorimetry provided comparable energy-expenditure measurements during this period. Finally, when the subject was refed a controlled energy intake of 7950 kJ/d for 21 d, body weight and fat losses were observed. Therefore, these observations do not support the validity of the low energy intake that may be reported by people predisposed to obesity. PMID- 1877507 TI - Skeletal muscle density: effects of obesity and non-insulin-dependent diabetes mellitus. AB - Obesity is associated with increased lean mass but its effects on lean-tissue density are less clear. To examine the effects of obesity and non-insulin dependent diabetes mellitus (NIDDM) on lean-tissue composition and density, cross sectional computed tomography (CT) scans of the midthigh were obtained in 20 men of various weights. Obesity was associated with increases in thigh-adipose (r = 0.75) and lean-tissue volumes (r = 0.52) and with reduced density of lean tissue (r = -0.73). The increased lean tissue in obesity was due to a nonadipose tissue component with a density below the normal range of muscle, an effect compounded by NIDDM, whereas normal-density muscle volume was unchanged. PMID- 1877508 TI - Decreased stature associated with moderate blood lead concentrations in Mexican American children. AB - The relationship of blood lead concentration to stature was evaluated by examining data from a sample of 1454 Mexican-American children aged 5-12 y, derived from the data sets of the Hispanic Health and Nutrition Examination Survey (HHANES) conducted in 1982-1984. The results indicate that there is an inverse relationship between blood lead concentration in the range 0.14-1.92 mumol/L with stature. The present finding suggests that growth retardation may be associated even with moderate concentrations of blood lead. Therefore, permissible exposure levels of lead for children deserve reexamination in light of the present analysis. PMID- 1877509 TI - A new procedure to assess the energy requirements of lactation in Gambian women. AB - The combined 24-h energy expenditure (24-h EE) of mother and child was measured with a respiratory chamber (indirect calorimeter) in a group of 16 lactating Gambian women and was compared with that of a control group of 16 nonpregnant, nonlactating (NPNL) Gambian women. Breast-milk production (738 +/- 47 g/d: mean +/- SE) was adequate to allow a normal rate of growth of their 2-mo-old babies (28.0 +/- 2.4 g/d). The combined 24-h EE (mother and child) was higher (8381 +/- 180 kJ/d. P less than 0.001) than that of NPNL women (6092 +/- 121 kJ/d). Two thirds of this differences could be attributed to the child's EE and one-third to a greater spontaneous physical activity of lactating women. The energy retained by the child for growth in conjunction with the calorimetric measurements allowed the calculation of the extra energy requirements for lactation, which were found to be 2100 kJ/d. These results confirm the values of the current dietary recommendations for lactation, based on the energy cost of milk production. PMID- 1877510 TI - Digestion of bovine milk proteins in patients with a high jejunostomy. AB - Digestion of milk proteins was studied in short-bowel patients. After ingestion of water, purified beta-lactoglobulin (beta-Ig), or skim milk, effluents were collected at the stoma. The flow rate of the effluent peaked in the first 30-min period after ingestion and returned to the basal value within the first 60 min. After milk ingestion 1) the nitrogen concentration of effluents peaked in the first 30 min, 2) SDS-polyacrylamide gel electrophoresis and Western blot indicated the presence of beta-Ig and alpha-lactalbumin (alpha-lac) in jejunal effluents but only during the first 30 min whereas caseins were detected during the initial 1-2 h effluents, and 3) immunoenzymo metric assay indicated that 64% and 44% of the beta-Ig and alpha-lac, respectively, were recovered in an intact antigenic form. Results indicate that the digestion of milk proteins in humans differs quantitatively. Digestion appeared partially incomplete in the upper jejunum, suggesting the importance of the ileum for completion of digestion. PMID- 1877511 TI - Plasma response to oral beta-carotene in Guatemalan schoolchildren. AB - The response to oral doses of beta-carotene (0 mg, n = 10; 15 mg, n = 20; and 30 mg, n = 21) was studied in 51 Guatemalan children aged 8-15 y, with mean fasting plasma retinol concentrations of 1.72 +/- 0.38 mumol/L. Beta-carotene was delivered with a chocolate drink containing 8.4 g fat. Serial blood sampling was performed at intervals up to 48 h. Circulating retinol concentrations remained relatively constant. The maximum increases in plasma beta-carotene after the 30- and 15-mg doses for all subjects occurred at 24 h and were 0.29 and 0.23 mumol/L, respectively. Time of maximum increase for individuals varied and average maxima over the 48-h period for individuals were 0.13 and 0.26 mumol/L for the 15- and 30-mg-treatment groups, respectively. Increased plasma beta-carotene concentrations were not predicted by recent intake of dietary vitamin A, fasting plasma concentrations, or anthropometric measurements. PMID- 1877512 TI - Diarrhea, respiratory infections, and growth are not affected by a weekly low dose vitamin A supplement: a masked, controlled field trial in children in southern India. AB - Incidence, duration, and severity of diarrhea and respiratory symptoms were monitored weekly for 1 y in 15,419 children 6-60 mo of age in a randomized, placebo-controlled, masked clinical trial conducted in southern India. Half the children received weekly doses of 8.7 mumol (2500 microgram) vitamin A and 46 mumol (20 mg) vitamin E (treated) and the other half, 46 mumol vitamin E (control). Medical and ocular examinations and anthropometric measurements were obtained before and after 52 wk of intervention. Ocular examinations also were obtained after 26 wk. Supplements were delivered weekly from calibrated dispenser bottles by community health volunteers who also recorded each mother's recall of daily morbidity of her child during the previous week. Baseline characteristics of treated and control subjects were similar and documented a prevalence of 11% xerophthalmia and 72% undernutrition. Weekly treatment with the low-dose vitamin A supplement did not influence the incidence, severity, or duration of diarrhea or respiratory infections and did not influence linear or ponderal growth. PMID- 1877513 TI - Nutritional status of infants with cystic fibrosis associated with early diagnosis and intervention. AB - The purpose of this study was to characterize the nutritional status of infants diagnosed with cystic fibrosis (CF) through neonatal screening and to determine if they would achieve normal nutrition when managed with early intervention. In addition, nutrient intake was assessed to determine energy and macronutrient consumption patterns. Evaluation of growth revealed that normal patterns could be achieved with mean energy intake values at ages 6 and 12 mo of 481 and 426 kJ/kg body wt (115 and 102 kcal/kg body wt), respectively. Biochemical assessment demonstrated low alpha-tocopherol and linoleic acid values at diagnosis in the majority of infants whereas one-third had abnormal indices of protein nutriture. Essential fatty acid deficiency was also demonstrated at diagnosis by abnormal triene-tetraene ratio values in 27% of screened infants. With predigested formula and dietary supplementation, there was improvement in all indices of nutritional status and only a low percentage of patients showed mild biochemical abnormalities at age 12 mo. PMID- 1877514 TI - Carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus: effects of a low-fat, high-carbohydrate diet vs a diet high in monounsaturated fatty acids. AB - Nineteen patients affected by non-insulin dependent diabetes mellitus (NIDDM), in good glycemic control (fasting plasma glucose 7.2 +/- 0.3 mmol/L, glycosylated hemoglobin 6.3 +/- 0.2%), underwent three isocaloric dietary phases. In phases 1 and 3 the diet was rich in complex carbohydrates (Carbo) whereas in phase 2 it was rich in monounsaturated fatty acids (Mono). Plasma glucose concentrations were 7.1 +/- 0.3 and 7.2 +/- 0.3 mmol/L for the two Carbo phases and 7.5 +/- 0.4 mmol/L for the Mono phase (NS). Plasma total cholesterol values for the Carbo phases were 6.2 +/- 0.2 and 6.4 +/- 0.2 mmol/L, respectively, and 6.5 +/- 0.2 mmol/L on the Mono phase (NS). Similarly, no significant changes were noticed for plasma triglycerides and high-density-lipoprotein (HDL) cholesterol. Thus, both diets were well-tolerated and did not alter glucose homeostasis or worsen plasma lipid concentrations. Consequently, these results suggest that a wider dietary choice can be made available to NIDDM patients without producing unwanted side effects. PMID- 1877515 TI - Coronary-heart-disease risk-factor status of the Cretan urban population in the 1980s. AB - The traditional Cretan diet has been associated with low coronary-heart-disease (CHD) mortality rates. This study reports on the prevalence of CHD risk factors among 387 Cretan bank employees. Mean cholesterol concentration has risen by 36% over 26-y; dietary intake has changed: consumption of meat, fish, and cheese has increased and consumption of bread, fruit, and potatoes has decreased. Although the percentage contribution of fat to total energy intake has decreased from 40% to 36%, there has been a reduction in monounsaturated fatty acid consumption and an increase in the consumption of saturated fatty acids whereas the consumption of polyunsaturates has not been altered. Exception for diminished physical activity, the prevalence of other risk factors (smoking, blood pressure, and body mass index) remained relatively stable over this period. These changes in the CHD risk-factor status of the Cretan urban population occurred over a period in which CHD mortality rates are reported to have increased. PMID- 1877516 TI - Caffeinated and decaffeinated coffee effects on plasma lipoprotein cholesterol, apolipoproteins, and lipase activity: a controlled, randomized trial. AB - Coffee consumption has been associated with elevated plasma cholesterol. One hundred eighty-one men consumed a standard caffeinated coffee for 2 mo followed by randomization to continue caffeinated coffee (control), change to decaffeinated coffee or no coffee for 2 mo. Plasma low-density-lipoprotein (LDL) cholesterol and apolipoprotein B concentrations increased significantly (0.12 +/- 0.65 mmol/L, P less than 0.025; 0.06 +/- 0.12 g/L, P less than 0.0004, respectively) in the group that changed to decaffeinated coffee. In a subgroup (n = 51), post-heparin lipoprotein lipase decreased significantly more (-270 mmol free fatty acids.L-1.h-1, P less than 0.003) in the decaffeinated-coffee group. Resting heart rate and blood pressure did not change significantly. Change from caffeinated to decaffeinated coffee increased plasma LDL cholesterol and apolipoprotein B whereas discontinuation of caffeinated coffee revealed no change. This finding suggests that a coffee component other than caffeine is responsible for the LDL cholesterol, apolipoprotein B, and lipase activity changes reported in this investigation. PMID- 1877517 TI - Iodine and selenium deficiency. PMID- 1877518 TI - Fish-oil feeding decreases tumor growth? Odeleye and Watson revisited. PMID- 1877519 TI - Calcium supplementation and iron absorption. PMID- 1877520 TI - Protein turnover, experimental diets, and bed rest. PMID- 1877521 TI - Dietary supplements and work performance. PMID- 1877522 TI - Beta-carotene's effects on serum lipoproteins and immunologic indices in humans. PMID- 1877523 TI - Measurement of knee height in frail, elderly nursing home residents. PMID- 1877524 TI - Are the FAO/WHO/UNU predictive equations for resting metabolic rate accurate? PMID- 1877525 TI - The coming era of cytologic automation. PMID- 1877526 TI - Immunophenotyping of hematologic malignant conditions: to flow or not to flow? PMID- 1877527 TI - The efficacy of an automated preparation device for cervical cytology. AB - A new automated method for collecting and preparing cells for cytologic screening (termed the ThinPrep process) was tested. Four hundred forty-nine specimens prepared by ThinPrep and conventional methods were evaluated. This study compared specimen adequacy and detection of disease with the two methods. For the ThinPrep method, exfoliated cells were collected in suspension, gently dispersed, collected on a polycarbonate filter, and transferred to a glass slide. The ThinPrep method reduced the number of smears that lacked endocervical columnar cells by 24%. Significant improvement with the ThinPrep, versus the conventional method, also was found for detection of low-grade cervical intraepithelial lesions. Thus, the ThinPrep method improved specimen quality and reliability of cytologic detection of cervical neoplasia. PMID- 1877528 TI - Distribution of BCA-225 in adenocarcinomas. An immunohistochemical study of 446 cases. AB - BCA-225 is a glycoprotein identified in human breast carcinoma cells that has been reported to show a restricted distribution in other human tissues. To further define the presence of BCA-225 in human carcinomas, the authors performed an immunohistochemical study, applying a commercially available monoclonal antibody to BCA-225 to formalin-fixed, paraffin-embedded sections of 446 adenocarcinomas from a variety of sites. BCA-225 expression was found to be common in adenocarcinomas of the breast (98%), kidney (94%), ovary (80%), and lung (74%) but was infrequent in adenocarcinomas of the gastrointestinal tract (10-16%). Adenocarcinomas of the prostate, bile ducts, thyroid, endometrium, endocervix, and pancreas showed an intermediate frequency of BCA-225 expression (36-68%). Although rare tumor cells in three hepatocellular carcinomas showed reactivity for BCA-225, staining of more than 10% of the tumor cells was not seen in any of the 23 hepatocellular carcinomas that were studied. The authors conclude that BCA-225 is expressed commonly in human adenocarcinomas and that it is not a breast-specific antigen. Antibodies to BCA-225 may have utility in helping one to exclude hepatocellular carcinoma in certain clinical settings. PMID- 1877529 TI - Geographic variations in the histologic characteristics of the gastric mucosa. AB - Histologic sections of 205 gastrectomy specimens, which were obtained for benign and malignant diseases, were reviewed. All patients were Mexican nationals. The following histologic features were recorded: intestinal metaplasia, intramucosal cysts, ciliated gastric cells, and different types of pyloric cells ("ordinary"; with granular cytoplasm; with small cytoplasmic vacuoles; with large cytoplasmic vacuoles; or with homogeneous "glassy" cytoplasm). The percentage of specimens showing intestinal metaplasia was similar in those containing gastric ulcers (42.7%) or adenocarcinomas (50.0%). Intestinal metaplasia was decreased in men 59 years of age or older and in women 69 years of age or older. Diffuse-type adenocarcinoma accounted for 90% of the gastric tumors. Only 3 of the 205 specimens (1.9%) contained intramucosal cysts, and only 1 (0.4%) showed ciliated cells. Pyloric cells with granular cytoplasm were observed in 21.2% of the specimens, and pyloric cells with small cytoplasmic vacuoles were seen in 1.9%. Pyloric cells with large vacuoles or "glassy" cytoplasm were not found in any case. These results indicate differences in the proportions of several histopathologic findings in the gastric mucosa, between Mexicans and other ethnic groups that have been investigated in previous surveys. The authors' findings support the hypothesis that different environmental factors, acting in disparate geographic regions, may account for dissimilarities in the histologic appearance of "normal gastric mucosa." PMID- 1877530 TI - Primary carcinoid of the common bile duct. Immunohistochemical characterization of a case and review of the literature. AB - A 39-year-old woman with a primary carcinoid of the common bile duct is presented. The tumor showed argyrophilia; and, by immunohistochemical studies, chromogranin, serotonin, and somatostatin were demonstrated. The patient has no symptoms 42 months after surgical treatment. To the authors' knowledge, this is the first report of a carcinoid of the common bile duct as studied by immunohistochemistry. When six choledochal carcinoids were reviewed, the following characteristics were observed: in none of the cases were endocrine symptoms present; women were affected more frequently than men; the carcinoids occurred in younger patients than did adenocarcinomas; metastases were present in half of the patients; and, as a group, carcinoids seemed to have a better prognosis than adenocarcinomas in this location. PMID- 1877531 TI - Uterine leiomyoma with skeletal muscle differentiation. Report of a case. AB - Skeletal muscle differentiation is reported in a uterine leiomyoma from a 54-year old woman. Evidence of rhabdomyoblastic features included a typical light microscopic appearance, immunoreactivity with antimyoglobin antibodies by immunoperoxidase studies, and the presence of myofibrils by electron microscopic examination. The patient is well more than two years after surgery. PMID- 1877532 TI - Frozen sections of cellular lymphoid proliferations provide adequate DNA for routine gene rearrangement analysis. AB - Optimal use of frozen tissue procured as part of a thorough diagnostic workup of suspected lymphoma is important, and conservation of similar samples is a prerequisite for maintaining a large and varied frozen archive repository. The authors have evaluated a simple tissue-conserving method for the preparation of cellular lymphoid specimens for immunoglobulin and T-cell receptor gene rearrangement analysis. Initially, 16-microns-thick frozen tonsil sections were examined to determine adequacy for DNA extraction. Specimens containing three, six, and nine sections each were evaluated separately. DNA quantitation disclosed yields ranging from 84 to 204 micrograms (mean, 156 micrograms). The authors have used this technique on 24 cellular lymphoid proliferations from their frozen archives. Six to ten 16-microns sections were used, depending on tissue size. DNA quantitation ranged from 0 to 520 micrograms (mean, 135 micrograms). Twenty-one of 24 cases yielded adequate DNA for analysis; each showed appropriate germline or rear-ranged bands with respect to the particular morphologic diagnosis. Attempts to obtain adequate DNA with the use of this technique on skin biopsy specimens with lymphoid infiltrates resulted in overall poor yields; this may be because of dermal collagen or small sample size. This method of sample preparation provides adequate DNA for routine Southern blot hybridization analysis of cellular lymphoid tissues and offers the additional advantage of allowing preservation of frozen tissue for future study. PMID- 1877533 TI - An evaluation of three commercial fecal transport systems for the recovery of enteric pathogens. AB - Twenty-five isolates, including six strains of Shigella species, six strains of Salmonella species, five strains of Yersinia enterocolitica, six strains of Campylobacter jejuni, and two strains of Vibrio parahaemolyticus, were inoculated at a concentration of 1.5 x 10(4) colony-forming units/mL into the following transport systems: Fekal Enteric Plus (Trend Scientific, Inc., St. Paul, MN), Cary Blair Transport Medium (Remel, Inc., Lenexa, KS), and Para-Pak C & S (Meridian Diagnostics, Inc., Cincinnati, OH). The Fekal Enteric Plus system showed a greater than or equal to 50% recovery of the original bacterial inoculum after 96 hours for all Salmonella, Shigella, and Yersinia strains tested and after as long as 72 hours for Vibrio strains. The Cary Blair Transport System showed greater than or equal to 50% recovery of the initial inoculum at 96 hours for five of six Salmonella strains, four of six Shigella strains, all Yersinia strains, and one of two Vibrio strains. With the use of the Para-Pak C & S, greater than or equal to 50% recovery of the original inoculum after 96 h was demonstrated for five of six Salmonella strains, four of six Shigella strains, all Yersinia strains, and one of two Vibrio strains. All three systems did not demonstrate even 10% recovery of the initial C. jejuni inoculum at 24 hours when held at room temperature. PMID- 1877534 TI - Allergic fungal sinusitis. Report of three cases associated with dematiaceous fungi. AB - Most reported cases of allergic sinusitis have been attributed to Aspergillus, based on the morphologic features of the organisms in tissue sections. However, in most cases, cultures have not been done. This is a report of three cases of non-Aspergillus allergic fungal sinusitis. The patients' ages were 11, 16, and 43; two were male and one was female. Histopathologic study disclosed fungal organisms resembling Aspergillus. However, cultures of these patients' nasal secretions grew Drechslera, Exserohilum, and Bipolaris fungal organisms. The non Aspergillus nature of these infections was further supported by positive Fontana Masson melanin staining. The authors conclude that allergic fungal sinusitis most likely results from non- Aspergillus organisms. For definitive fungal identification, tissue culture is mandatory. When tissue is not cultured or no organisms grow, a Fontana-Masson stain can be a useful adjunct in fungal identification. PMID- 1877535 TI - Immunohistochemical expression of galactomannan in the cytoplasm of phagocytic cells during invasive aspergillosis. AB - The monoclonal antibody EB-A1 to galactomannan is apparently specific for detecting Aspergillus species and Penicillium marneffei in formalin-fixed, paraffin-embedded tissues. It reveals hyphae, remnants of filaments, and organisms in the cytoplasm of some phagocytic cells. PMID- 1877536 TI - The impact of a clinic for adults with HIV infection on the microbiology laboratory. AB - The Infectious Diseases Clinic (IDC) discussed serves adults who are seropositive for human immunodeficiency virus. The authors reviewed the outpatient and inpatient microbiology tests of a three-month period during 1989 for a systematic sample of IDC patients. The 249 patients in the sample had 682 microbiology tests performed during the period (mean 2.7 tests per patient). Tests most frequently requested were mycobacterial culture, routine blood culture, and cryptococcal antigen determination. Patients with acquired immunodeficiency syndrome (43% of IDC patients) accounted for 63% of the requested IDC tests. IDC patients comprised about 2.4% of patients served but accounted for 3.9% of the requested microbiology tests and 6.6% of the microbiology work load for reported tests. Using Centers for Disease Control case projections, the authors estimated that services to IDC patients in 1993 would comprise 6.6% of all microbiology tests and 10.6% of the microbiology work load. The implications of these data for microbiology probably also apply to other laboratory testing and emphasize the need for more efficient ways to use and perform diagnostic studies required by patients with HIV infection. PMID- 1877537 TI - Failure of dithiothreitol and pronase to reveal a false-positive cryptococcal antigen determination in cerebrospinal fluid. AB - A patient with squamous cell carcinoma of the lung and a serum rheumatoid factor (RF) of 1:1,280 had a positive cerebrospinal fluid (CSF) latex agglutination test (LAT) for cryptococcal antigen, in culture-negative, India-ink-negative CSF. Pretreatment of the sample of CSF with 2-mercaptoethanol (2-ME) ablated the antigen titer and established the presence of a false-positive LAT, whereas CSF pretreated with dithiothreitol (DTT) and pronase continued to yield a false positive result. The differing ability of pronase, DTT, and 2-ME to eliminate interfering substances from CSF has not been previously described. Moreover, because RF is unlikely to cross the blood-brain barrier, the authors postulated that malignant disease was responsible for the patient's false-positive LAT in CSF. Hence, the authors report the case to emphasize that false-positive LAT results in CSF are unlikely to be produced by RF and to underscore the benefit of using enzymatic and sulfhydryl-reducing agents when the validity of the initial test results are in doubt. Such a procedure will optimize the chances of accurately identifying false-positive LAT results in CSF. PMID- 1877538 TI - Rapid removal of heparin from plasma by affinity filtration. AB - Coagulation test abnormalities caused by the presence of heparin are not uncommon and frequently result in additional laboratory investigation and unwarranted therapy. Methods to neutralize the effect of heparin include the addition of polyanions, enzymes, or resins to the clinical samples. These techniques are time consuming and cumbersome and produce inconsistent results. As an alternative, use of a positively charged porous filtration medium to remove heparin from the sample is described. The filtration procedure requires less than one minute and provides a consistent and total removal of heparin at plasma concentrations in excess of therapeutic levels. Chromogenic substrate analysis for residual heparin activity confirms total removal of the drug at levels greater than one unit/mL of plasma. In clinical trials, filtration normalized the activated partial thromboplastin time (APTT) of all patient specimens containing heparin (n = 41). Filtration did not shorten the coagulation assay times of patients receiving warfarin (n = 36) or of those with a variety of acquired coagulopathies (n = 14). The level of coagulation factors adsorbed to the filter medium compares favorably to that adsorbed by other commercially available heparin-binding resins. Routine use of the filter in the clinical laboratory allows for the rapid and definitive identification of heparin in specimens with prolonged coagulation times and provides clinically meaningful data. PMID- 1877539 TI - Plasmapheresis. A therapeutic option in the management of heparin-associated thrombocytopenia with thrombosis. AB - Heparin-associated thrombocytopenia with thrombosis (HATT) is an uncommon syndrome that is estimated to occur in 1-5% of patients with heparin-induced thrombocytopenia. Early diagnosis requires careful clinical surveillance, and the management of these patients can be complex. Cessation of heparin therapy and substitution or addition of oral anticoagulants, antiplatelet agents, dextrans, and prostacyclin analogues have been advocated. The authors are aware of only two case reports in the literature that examine the use of plasmapheresis as a therapeutic alternative. The authors report a case of a 53-year-old white man who developed HATT after a single protamine-reversed exposure to heparin. Controlled platelet aggregation studies performed before and after apheresis sessions documented a dramatic response and rapid normalization of platelet number and function in the patient. The authors conclude that plasmapheresis could be a valuable adjunct in the successful management of patients with HATT. When done in conjunction with platelet aggregation studies, an objective measurement of therapeutic efficacy can be achieved. PMID- 1877540 TI - Air-exposed urine dipsticks give false-positive results for glucose and false negative results for blood. AB - Urine dipstick jars often are left uncapped, which led the authors to wonder what effect prolonged air exposure might have on dipstick accuracy. Unexpired Ames Multistixs (Miles Inc., Elkhart, IN) were exposed to ambient air for intervals of up to eight weeks and were used to test urine for the presence or absence of blood, protein, and glucose. Multistixs were read by a blinded participant. A urine sample reading negative for glucose with unexposed (control) Multistixs tested trace positive with three of three Multistixs exposed for 7 days, and 1+ (three of six) or trace positive (three of six) (P less than 0.05) with Multistixs exposed for 28 days. A urine sample reading 1+ for blood with controls tested negative with five of six (P less than 0.05) and six of six (P less than 0.05) Multistixs exposed for 28 and 56 days, respectively. Protein detection was accurate up to 56 days. The authors conclude that urine dipstick jars should be recapped to avoid prompting needless evaluations of glucosuria or delaying detection of important causes of microscopic hematuria. PMID- 1877541 TI - How should bromodeoxyuridine labeling be counted? PMID- 1877542 TI - Gene rearrangements in the diagnosis of lymphoma/leukemia. PMID- 1877543 TI - Chromosomal abnormalities in a low-grade B-cell lymphoma of mucosa-associated lymphoid. PMID- 1877544 TI - Nasal considerations in orthognathic surgery. AB - The functional correction of dentofacial deformities by orthognathic surgery produces major changes in facial appearance. Facial esthetics must therefore be equally appreciated by the orthodontist and the maxillofacial surgeon. The orthodontist must perform a thorough esthetic facial evaluation along with his usual orthodontic evaluation. The treatment plan must then be based on the esthetic evaluation and knowledge of the facial changes caused by orthodontic treatment and skeletal jaw surgery. Central to facial form is the nose. This article will outline the proper functional and esthetic evaluation of the nose in relation to the face. Nasal and upper lip changes associated with maxillary procedures will also be covered in detail. In light of these two areas, proper treatment planning and sequencing will be discussed. PMID- 1877545 TI - Consistency of orthodontic treatment decisions relative to diagnostic records. AB - The purpose of this study was to evaluate how incremental information obtained from different types of diagnostic records contributes to the determination of orthodontic treatment decisions. Pretreatment records of 57 orthodontic patients were assessed by five orthodontists who were part-time faculty members and also in private practice. This sample consisted of dental school orthodontic patients who had Class II malocclusions and included patients at three different dental developmental stages. The following diagnostic records were used: study models (S), facial photographs (F), a panoramic radiograph (P), a lateral cephalogram (C), and its tracing (T). Five combinations of diagnostic records were presented to the orthodontists in the following sequence: (1) S; (2) S + F; (3) S + F + P; (4) S + F + P + C; and (5) S + F + P + C + T. The simultaneous interpretation of all diagnostic records (S + F + P + C + T) was used as the "diagnostic standard." There was a diagnostic standard for each of the patients and for each of the orthodontists. The diagnostic standard was achieved: (1) S = 54.9%, (2) S + F = 54.2%, (3) S + F + P = 60.9%, and (4) S + F + P + C = 59.9%. Thus, in a majority of cases (55%), study models alone provided adequate information for treatment planning, and incremental addition of information from other types of diagnostic records made small differences. PMID- 1877546 TI - The nature of Class II relapse after Herbst appliance treatment: a cephalometric long-term investigation. AB - The purpose of this investigation was to assess the number of, and the interrelation between, skeletal and dental components that contribute to Class II relapse after Herbst treatment. A comparison was made between 15 relapse and 14 stable cases at least 5 years after treatment. Lateral cephalograms taken before and immediately after Herbst treatment, as well as 6 months and 5 to 10 years after treatment, were analyzed. The results revealed that relapse in the overjet and sagittal molar relationship resulted mainly from posttreatment maxillary and mandibular dental changes. In particular, the maxillary incisors and molars moved significantly (p less than 0.05) to a more anterior position in the relapse group than in the stable group. The interrelation between maxillary and mandibular posttreatment growth was favorable and did not contribute to the occlusal relapse. It is hypothesized that the main causes of the Class II relapse in patients treated with the Herbst appliance were a persisting lip-tongue dysfunction habit and an unstable cuspal interdigitation after treatment. PMID- 1877547 TI - Perception of personal dental appearance in young adults: relationship between occlusion, awareness, and satisfaction. AB - Information about the individual perception of a patient's own occlusion is considered of importance in orthodontics. One hundred thirty young adults (mean age, 18.1 years) were clinically examined and interviewed with the purpose of relating self-awareness and satisfaction to the actual occlusal status and determining whether dissatisfaction is based on realistically perceived anomalies. From study casts taken at the time of examination, six anterior traits were recorded as either malocclusion, minor deviation, or near-ideal occlusion according to two sets of criteria. Self-awareness was assessed by analyzing agreement between the subjects' reports on the presence of the six traits and the corresponding recordings. Satisfaction was evaluated from three questions with fixed alternative answers. The majority of the young adults (63%) were characterized as having near-ideal occlusion or only minor deviations. Only mild and moderate malocclusions were present in the sample since severe malocclusions are routinely treated during childhood. The subjects were generally aware of anterior traits. Almost all the subjects (98%) with near-ideal occlusion or minor deviations expressed satisfaction. Malocclusion was present in 14 of the 16 subjects who were dissatisfied, and dissatisfaction was based on realistically perceived anomalies. However, traits rated as malocclusion were present in 30% of the satisfied subjects, which may in part be explained by the mild degree of malocclusion in the sample. Awareness of occlusal traits varied among the satisfied subjects. PMID- 1877548 TI - Comment on a review article. PMID- 1877549 TI - Comment on malpractice suits. PMID- 1877550 TI - Nitinol alloys: so, who's on first? PMID- 1877551 TI - Shear, torsional, and tensile bond strengths of ceramic brackets using three adhesive filler concentrations. AB - The effect of changes in adhesive filler concentration on the shear, torsional, and tensile bond strength of a chemical, a mechanical, and a chemical/mechanical retained ceramic bracket was evaluated. Two hundred ten bovine teeth were bonded with one of three ceramic brackets using a 30%, 55%, or 80% filled adhesive. The brackets were debonded with a shear, torsional, or tensile force to test the bond strength and the site of bond failure. No significant difference was found in the shear, torsional, or tensile bond strength of each ceramic bracket type in relation to changes in the adhesive filler concentration. However, there was a trend toward increased bond strength with increasing filler concentration. Combining the data according to adhesive type revealed that the 80% filled adhesive displayed a significantly greater shear bond strength than the 30% or 55% filled adhesive and a greater torsional bond strength than the 30% filled adhesive. This supports the hypothesis of increased bond strength with increased adhesive filler concentration. The mechanically retained ceramic bracket showed greater shear bond strength and maximum shear bond strength in torsion than the chemical or chemical/mechanical retained ceramic bracket. The tensile bond strength of the mechanically retained ceramic bracket was similar to that of metal brackets reported in other studies, and the failure site was at the bracket adhesive interface. PMID- 1877552 TI - Alterations of hyoid bone position and pharyngeal depth and their relationship after surgical correction of mandibular prognathism. AB - The present investigation studied changes of hyoid bone position and pharyngeal depth at the levels of the second and fourth cervical vertebrae and their relationships in mandibular prognathism patients who received combined orthodontic-surgical treatment. The material consisted of presurgical and 1-year postsurgical profile cephalograms of 52 adult orthognathic surgery patients (40 females and 12 males) who initially had mandibular prognathism and had undergone bilateral vertical ramus osteotomy through an extraoral incision in the retroangular area. Hyoid bone position and pharyngeal depth were assessed on the profile radiographs with 10 cephalometric variables. Paired t tests were used to evaluate the operative changes in all cephalometric parameters. The relationships between pairs of variables describing hyoid bone position and pharyngeal depth were assessed by means of Pearson's product-moment correlation analysis. Significant differences (p less than 0.01) were observed for the distances of the hyoid bone to the maxilla and the mandible. The distances of the hyoid bone with the anterior cranial base, the vertebral column, and the anterior pharyngeal wall, and the measurements representing pharyngeal depth exhibited no significant changes (p greater than 0.05). Moderate correlations were seen between (1) the depth of the pharynx at the fourth cervical vertebra and the hyosymphyseal distance (r = 0.34) and the distance between the point of the projection of the hyoid bone to the mandibular line with its posterior border (r = -0.34), and (2) the depth of the pharynx at the second cervical vertebra and the distance of the hyoid bone with the anterior pharyngeal wall at the level of the fourth cervical vertebra (r = -0.33).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877553 TI - Adaptability of the adult primate craniofacial complex to asymmetrical lateral forces. AB - The adaptability of the adult craniofacial skeleton to altered functional relationships has been reported. An experimental quantification of these changes is lacking, however, and the possible underlying mechanisms of the alterations have not been explained. The purpose of this investigation was to evaluate the effect that lateral displacement of the mandible has on the dentoalveolar, craniofacial, and neuromuscular system in the adult rhesus monkey. Ten adult monkeys were studied; five served as controls, three were fitted with bilaterally inclined mandibular splints designed to deviate the mandible toward the left on closure, and two animals had flat splints to provide even occlusal contact. Pretreatment and posttreatment assessment of dentoalveolar and craniofacial change was made from mounted study casts, cephalometric head films, electromyograms and computed tomograms. Axial computed tomographic scans were used to evaluate potential changes in bone density at the lower part of the mandible, the condyle, the coronoid process, the neck of the condyle, and the zygomatic arch by means of a one-way analysis of variance. Changes in the measured variables were not observed in the control animals or in the animals with flat splints. Animals with inclined splints, however, demonstrated attrition and intrusion of maxillary molars and mild proclination of the maxillary incisors. Posttreatment computed tomographic scans in these animals showed significantly increased bone density in the right coronoid process (p less than 0.05) and bilaterally at the necks of the condyles (p less than 0.005). Resting electromyographic activity remained low and was not significantly different among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877554 TI - Skeletal, dental, and functional effects of headgear-activator therapy on Class II malocclusion in Japanese: a clinical case report. AB - Ten orthodontic patients in whom a headgear-activator appliance was used in the first phase of treatment for Class II malocclusion were clinically evaluated. All patients had abnormal perioral muscle function at the initial examination. Myofunctional methods were used before and during active treatment. Pretreatment and posttreatment cephalometric tracings were evaluated to examine the effect of the appliance on dental, skeletal, and soft tissue structures. Five of the 10 cases illustrated distal movement of the lower first molar, a phenomenon not mentioned previously in the literature. Growth stimulation of the mandible was also observed in this patient sample, with some subjects demonstrating above average mandibular growth when compared with a control group of normal subjects. Abnormal oral function was eliminated, and all patients had clinically acceptable results at the end of the treatment period. The headgear-activator appliance can be considered an effective tool for the control of vertical growth problems in growing mixed-dentition patients. PMID- 1877555 TI - In memoriam. Earl has gone home. PMID- 1877556 TI - Support services for pediatric trainees. A survey of training program directors. AB - We conducted a survey of pediatric training program directors (75% response rate) regarding program support services for house staff, directors' attitudes about stress in training, and program plans to ameliorate such stress. Support services included explicit measures to alleviate stress, policies that may minimize stress, evaluation of house staff performance, feedback regarding career concerns, and benefits (eg, medical insurance and child care). Most programs offered services to reduce stress from training, but few offered preventive services. Support policies were reported to be inadequate, especially in the areas of coverage for leaves of absence. Maternity leave represented most leaves of absences, as 10% of the female house staff and 11% of the male house staff members became parents. Program directors' terms were short, and only 30% perceived these roles to be their primary roles. Male directors believed that female house officers had a harder time adjusting to their programs. We suggest changes and present a simple way for program directors to evaluate their support services. PMID- 1877557 TI - Optimal positioning of endotracheal tubes for ventilation of preterm infants. AB - Accurate knowledge of upper-airway dimensions is required to prevent malpositioning of endotracheal tubes in preterm infants. We measured vocal cord carina, oral-carina, and nasal-carina distances in situ at autopsy of two groups of infants (less than 1000 and greater than or equal to 1000 g). In all 24 infants, crown-heel length, crown-rump length, and occipitofrontal circumference were better than weight in predicting upper-airway dimensions. Flexion of the neck decreased and extension increased both nasal-carina and oral-carina distances. Lateral rotation produced no significant changes. The postmortem data were not different from nasal-carina distances measured radiologically in 40 living, nasally intubated and ventilated infants, confirming the clinical validity of our findings. Regression equations were derived to predict optimal endotracheal tube lengths based on the external measurements of crown-rump length and crown-heel length. PMID- 1877558 TI - Evaluation of auditory brain-stem response in full-term infants of cocaine abusing mothers. AB - The purpose of this study was to examine the association between perinatal cocaine exposure and the prevalence of hearing deficit in the newborn. Auditory brain-stem response testing was performed on 50 infants of cocaine-abusing mothers and 50 control infants. All infants were born at full term. Cocaine exposed infants had lower birth weights and a greater incidence of maternal tobacco and alcohol use. No differences were found in size, method of delivery, Apgar scores, or use of other illicit substances. Four infants of cocaine-abusing mothers and two control infants failed initial auditory brain-stem response testing. There were no differences in absolute or interpeak latencies of waveforms noted between the two groups. These data suggest that there is no increased incidence of hearing deficit as determined by auditory brain-stem response in newborns of cocaine-abusing mothers born at term and without other risk factors. PMID- 1877559 TI - Ductal patency in neonates with respiratory distress syndrome. A randomized surfactant trial. AB - The purpose of this study was to evaluate in a controlled study the effect of exogenous surfactant on various manifestations of ductal patency. Premature infants with respiratory distress syndrome were randomized to receive surfactant (Survanta) (n = 22) or air (n = 14). In neonates receiving surfactant, there was a greater tendency for an audible murmur to develop (13 of 22 vs four of 14). In spite of this, the clinical use of indomethacin was similar for the two groups, 10 (45%) of 22 vs six (43%) of 14. Excluding neonates given indomethacin early, a comparable number of surfactant-treated neonates (9/17 [53%]) vs control neonates (6/12 [50%]) demonstrated spontaneous closure of the ductus within a physiologic time frame (on or before day 4). For the gestational ages studied, the beneficial effects of exogenous surfactant were not associated with either an increased risk for delayed closure of the ductus arteriosus or a greater incidence of indomethacin usage. Utilization of exogenous surfactant does not appear to have an adverse impact on ductal patency. PMID- 1877560 TI - Safety of a preadolescent basketball program. AB - A preadolescent youth basketball program was prospectively studied to determine injury rates and the kinds of injuries sustained. The overall injury rate was 7.6% (39 injuries among the 510 children aged 5 to 12 years). Girls had a higher injury rate than boys (P less than .02). Only 12 children (2.4%) suffered significant injuries as defined by the inability to play for at least one session. Most injuries were contusions (35.9%), followed by strains or sprains (28.2%), epistaxis (12.8%), lacerations (5.1%), and one finger fracture (2.6%), the most significant injury. Games were more likely to produce injuries than practice sessions; most injuries occurred in the second half of game play. This study documents a low injury rate in an organized preadolescent basketball program. PMID- 1877561 TI - Decreasing severity of chronic uveitis in children with pauciarticular arthritis. AB - We compared the current prevalence and severity of chronic uveitis in children with pauciarticular juvenile rheumatoid arthritis in Seattle, Wash, with that of children with the same condition in the same area in 1975. The prevalence of eye disease decreased from 45% in 1975 to 13% in 1989, and the proportion of patients with severe visual loss decreased from 21% in 1975 to none in 1989. We could not attribute these findings to differences in known risk factors for iritis, such as age, sex, or presence of antinuclear antibodies. There was no difference in the duration of follow-up between the two groups. It is possible that the decline in prevalence of uveitis reflects a referral bias for eye disease in the 1975 population. However, the decrease in disease severity remains unexplained and may represent more effective treatment, earlier surveillance for ocular disease, or a change in the frequency of ocular manifestations of this disease in the 1989 group. PMID- 1877562 TI - Family history of myocardial infarction and hemodynamic responses to exercise in young black boys. AB - The influence of family history of coronary artery disease on children's hemodynamic responses to exercise was examined with 25 black boys aged 7 to 10 years. Blood pressure, heart rate, cardiac output, stroke volume, and total peripheral resistance were evaluated during preexercise, peak exercise, and recovery stages. Children with a family history of CAD exhibited greater systolic blood pressure and total peripheral resistance during preexercise and peak exercise stages than did those without a family history of coronary artery disease. After controlling for preexercise differences, the group with a family history of coronary artery disease exhibited greater increases in systolic blood pressure and less attenuation of total peripheral resistance to peak exercise than the group without a family history of coronary artery disease. Cardiac output indexed by body surface area and stroke volumes were higher at all times in the group without a family history compared with the group with a family history of coronary artery disease. Findings are compared with those of adult studies in terms of influence of family history of coronary artery disease on cardiovascular reactivity to stress. PMID- 1877563 TI - Physiologic responses to playing a video game. AB - The displacement of sports and other physical activities by television and video may contribute to the associations among television viewing, obesity, and reduced physical fitness. Because video games are widely played by children and adolescents, we assessed the metabolic and cardiovascular responses to video game playing. Heart rate, blood pressure, and oxygen consumption were measured serially over 30 minutes in 32 males and females aged 16 to 25 years (mean +/- SEM, 20 +/- 1 years) while they played the "Ms Pac-Man" video game under standard laboratory conditions and compared with measurements made in a standing but inactive position. Playing the video game significantly increased heart rate, systolic and diastolic blood pressure, and oxygen consumption. Energy expenditure increased from 6.08 +/- 0.24 kJ/min while the subjects stood inactive to 10.94 +/ 0.49 kJ/min while they played. The increase in metabolic rate and cardiovascular stimulation was similar in magnitude to mild-intensity exercise. PMID- 1877564 TI - Arterial catheter-related infections in children. A 1-year cohort analysis. AB - To determine the incidence of infection secondary to arterial catheterization in children as well as the risk markers, we prospectively evaluated, during a 1-year period, all arterial catheters installed in children admitted to the pediatric intensive care unit. A total of 340 cannulas were placed in 310 children aged 80 +/- 4 months (mean +/- SEM) for a period of 64 +/- 4 hours. Most catheters were inserted percutaneously (99%) in the radial artery (86.5%). Ninety-two percent (313/340) of the catheters were sterile (group 1), 5% (17/340) were contaminated (less than 10 colony-forming units on semiquantitative culture) (group 2), and 3% (10/340) were considered either locally infected (ie, greater than or equal to 10 colony-forming units) (eight of 10) or associated with a possible catheter related sepsis (two of 10) (group 3, or infected group). The incidence of local inflammation at the insertion site was higher in group 2 than in group 1 (18% vs 2.9%) but not statistically different between groups 3 and 1 (10% vs 2.9%). The duration of arterial catheterization was longer in group 3 than in group 1 (125 +/- 31 vs 61 +/- 4 hours). The risk of infection was nonexistent in the first 48 hours of catheterization. Thereafter it was calculated as being 6.2% (10/161), but it correlated poorly with the duration of arterial catheterization. These results confirm the very low incidence of infection related to arterial catheterization in children. Thus, routine catheter reinsertion is, in our opinion, unjustified. PMID- 1877565 TI - Radiological case of the month. Congenital syphilis. PMID- 1877566 TI - Picture of the month. Subcutaneous fat necrosis of the newborn. PMID- 1877567 TI - Lichen sclerosus et atrophicus in children. AB - The symptoms, findings, associated conditions, and treatment of lichen sclerosus et atrophicus were studied in 10 girls and one boy. Lichen sclerosus et atrophicus is a benign but chronic condition of the anogenital area of girls and, less frequently, of boys. The characteristic lesions are hypo-pigmented plaques in a figure-of-8 pattern surrounding the vulva and anus and often involving the natal cleft. The affected hypopigmented skin is sharply demarcated from the normal skin. Hemorrhagic, bullous lesions are uncommon. Fissures and ulcers are seen on the labia, between the labia, and on the perineum, anus, and natal cleft in many children and on the glans penis in boys. Lichen sclerosus et atrophicus causes painful defecation and anal and vulval bleeding. In two patients, one girl and one boy, anal stenosis due to lichen sclerosus et atrophicus and laxative treatment developed. Lichen sclerosus et atrophicus mimics sexual abuse and has led to false accusation and investigations. The anogenital lesions cleared in three patients at the ages of 9, 11, and 12 years, but lesions can persist into adulthood. PMID- 1877568 TI - Treatment of ulcerated hemangiomas with the pulsed tunable dye laser. AB - Hemangiomas are the most common tumor of infancy and are characterized by rapid growth during the first 6 months of life. During the rapid growth phase, approximately 5% to 10% of the hemangiomas ulcerate. Ulcerated lesions are painful, may bleed, and are at risk for bacterial infection. Previous therapy has included daily local wound care, topical antibiotics, and local and systemic steroids. We treated nine infants (eight female and one male) with ulcerated hemangiomas by means of a vascular-specific (585-nm) pulsed (450-microsecond) tunable dye laser. Eight of the nine patients had a single ulceration, whereas one patient had two ulcerations within a large hemangioma. Six of the ulcerations healed with a single laser treatment. One ulceration required two treatments to heal, and the remaining two required three treatments. Pain was subjectively decreased within 2 to 3 days in all patients after a single treatment. The pulsed tunable dye laser should be considered in the treatment of all ulcerated hemangiomas. PMID- 1877569 TI - Family physicians and neonatology. PMID- 1877570 TI - Misdiagnosis of Reye's-like illness. PMID- 1877571 TI - Congenital syphilis associated with negative results of maternal serologic tests at delivery. PMID- 1877572 TI - Response of seronegative adults to measles immunization. PMID- 1877573 TI - Improvement of leukemic hyperleukocytosis with only fluid and allopurinol therapy. PMID- 1877574 TI - Myopathy associated with ketoconazole treatment. PMID- 1877575 TI - Gallstones in children. PMID- 1877576 TI - Obesity and body-mass index. PMID- 1877577 TI - The clinic attending: teaching strategies for patient encounters. PMID- 1877578 TI - Water intoxication. A prevalent problem in the inner city. PMID- 1877579 TI - Oral water intoxication in infants. An American epidemic. AB - Between 1975 and 1990, a total of 34 patients with water intoxication were treated at St Louis (Mo) Children's Hospital, 24 of these in the last 3 years, indicating a marked increase in incidence of this previously rare condition. Thirty-one were infants living in poverty who ingested excessive amounts of water offered at home by their caretakers. Exhaustion of the supply of infant formula was the most common reason given for this substitution. Infants were treated by a single infusion of hypertonic saline or a slow infusion of isotonic saline. Central pontine myelinolysis was not observed as a complication of hypertonic saline therapy. Modification of the Special Supplemental Food Program for Women, Infants, and Children to provide sufficient formula for the growing infant and better education of mothers as to the hazards of excessive water ingestion might reduce the incidence of this preventable and life-threatening condition. PMID- 1877580 TI - Vasopressin levels in infants during the course of aseptic and bacterial meningitis. AB - We measured urine vasopressin (VP) once daily on days 1 through 3 in 18 patients hospitalized with meningitis. Urine VP values were 215 +/- 100, 116 +/- 44, and 69 +/- 23 pg/mL on days 1 through 3, respectively, for children with bacterial meningitis and 34 +/- 14, 20 +/- 4, and 15 +/- 4 pg/mL for those with aseptic meningitis. Urinary VP levels of infants with bacterial meningitis were significantly greater than those of healthy ambulatory subjects (n = 18) on all three study days; VP values of infants with bacterial meningitis were also greater than those of infants with aseptic meningitis on study days 2 and 3. The VP levels for the subjects with aseptic meningitis were significantly greater than those of the controls on day 1 only. None of the infants exhibited the clinical syndrome of inappropriate antidiuretic hormone secretion. PMID- 1877581 TI - Demographic and risk factors associated with chronic dieting in adolescents. AB - A comprehensive, school-based survey was administered to 36,320 Minnesota public school students in grades 7 through 12 during the 1987-1988 school year. Self reported chronic dieting was much higher in girls than in boys (12.1% of all girls vs 2.1% of boys). For girls, the percentage of chronic dieters was significantly less in grades 7 and 8 (7.8%) than in grades 9 and 10 (13.5%) or grades 11 and 12 (14.3%). There were no differences among urban, suburban, or rural youth. Black girls were less likely to diet compared with white girls. Chronic dieters were more likely than other students to report maladaptive weight loss techniques, such as self-induced vomiting (relative risk, 9.92 for girls and 9.40 for boys), laxative use (relative risk, 7.18 for girls and 11.00 for boys), ipecac use (relative risk, 8.33 for girls and 11.00 for boys), and diuretic use (relative risk, 7.30 for girls and 13.5 for boys). It is suggested that chronic dieting may serve as a screening marker for more severe eating and weight-loss behaviors. PMID- 1877582 TI - The effect of valproic acid on plasma carnitine levels. AB - Plasma total, free, and acyl carnitine levels were determined in four groups of children: (1) those treated with valproic acid as monotherapy (n = 43), (2) those treated with valproic acid plus other antiepileptics as polytherapy (n = 91), (3) those treated with other antiepileptic drugs alone (n = 43), and (4) normal patients (n = 89). The mean free carnitine level was significantly lower in both the valproic acid monotherapy (29.9 mumol/L) and polytherapy (21.4 mumol/L) groups compared with normal subjects (36.8 mumol/L); it was also significantly lower than that in patients treated with other antiepileptic drugs (36.7 mumol/L). Comparison of valproic acid polytherapy and monotherapy yielded significantly lower free carnitine levels in the polytherapy group. The ratios of acyl to free carnitine for monotherapy (0.41) and polytherapy (0.45) were significantly higher than that in the normal group (0.25). This study indicates that a general decrease in the carnitine pool should be anticipated in patients taking valproic acid polytherapy and, to a lesser degree, monotherapy. Carnitine levels in the group taking other drugs did not differ from normal. PMID- 1877583 TI - Effect of long-term community health education on body mass index. The Stanford Five-City Project. AB - Being overweight is a risk factor for cardiovascular heart disease and other medical problems. The purpose of this study was to examine the effect of a community-wide cardiovascular risk reduction trial (the Stanford Five-City Project) on body mass index. In the Stanford Five-City Project, two treatment cities (n = 122,800) received a 6-year mass media and community organization cardiovascular risk reduction intervention. Changes in the treatment cities were compared with two control cities (n = 197,500) for changes in knowledge of risk factors, blood pressure, plasma cholesterol level, smoking rate, body mass index, and resting pulse rate after 5-1/3 years of the education program. Both cohort and cross-sectional (independent) samples were used in the study. In the independent surveys, subjects in the treatment communities gained significantly less weight than subjects in the control communities (0.57 kg compared with 1.25 kg) over 6 years. In the cohort, there were no significant overall differences. The study provides some evidence that a community health education program may help reduce weight gain over time, but more effective methods must be developed if this important risk factor is to be favorably affected in broad populations. PMID- 1877584 TI - Carotid atherosclerosis measured by B-mode ultrasound in populations: associations with cardiovascular risk factors in the ARIC study. AB - To assess whether carotid atherosclerosis measured by B-mode ultrasound is related to cardiovascular risk factors, 386 cases with carotid artery wall thickening and an equal number of controls free of arterial intima-media thickening were drawn from the cohort of the Atherosclerosis Risk in Communities (ARIC) Study examined in four communities in the United States between 1988 and 1990. Cases and controls were individually matched on sex, race, age group, study center, and date of examination. The mean values of total cholesterol, low density lipoprotein (LDL) cholesterol, total triglyceride, blood pressure, and pack-years of cigarette smoking were higher in cases than controls. Mean high density lipoprotein (HDL) cholesterol was lower in cases than controls. Case control differences were all statistically significant. Multivariable-adjusted odds ratios point to differences of considerable magnitude in the risk of carotid atherosclerosis between groups defined by clinical and public health-oriented risk factor cut-points. PMID- 1877585 TI - Serum copper and the risk of acute myocardial infarction: a prospective population study in men in eastern Finland. AB - The authors investigated the association of serum copper concentration with the risk of acute myocardial infarction in 1,666 randomly selected men aged 42, 48, 54, or 60 years who had no symptomatic ischemic heart disease at entry. Baseline examinations in the Kuopio Ischaemic Heart Disease Risk Factor Study in Eastern Finland were done during 1984 to 1988. In Cox multivariate survival models adjusting for age, examination year, ischemic electrocardiogram in exercise, maximal oxygen uptake, diabetes, family history of ischemic heart disease, cigarette-years, mean systolic blood pressure, serum high density lipoprotein (HDL) cholesterol subfraction HDL2 and low density lipoprotein (LDL) cholesterol concentrations and blood leukocyte count, serum copper concentration in the two highest tertiles (1.02-1.16 mg/liter and 1.17 mg/liter or more) associated with 3.5-fold (95% confidence interval (Cl) 1.3-9.4, p less than 0.05) and 4.0-fold (95 percent Cl 1.5-10.8, p less than 0.01) risk of acute myocardial infarction. These data indicate that high copper status, reflected by elevated serum copper concentration, is an independent risk factor for ischemic heart disease. PMID- 1877586 TI - Effects of urban air pollution on emergency room admissions for chronic obstructive pulmonary disease. AB - The authors assessed the relation between sulfur dioxide and other air pollutants (black smoke, carbon monoxide, nitrogen dioxide, and ozone) and daily emergency room admissions for chronic obstructive pulmonary disease in Barcelona, Spain, during 1985-1986. Barcelona is a Mediterranean city of 1.7 million inhabitants that has air pollution levels lower than standard values. A weak but statistically significant association between emergency room admissions and levels of sulfur dioxide, black smoke, and carbon monoxide was observed. Daily emergency room admissions for chronic obstructive pulmonary disease increased by 0.02 and 0.01 for each microgram of sulfur dioxide and black smoke per cubic meter, respectively, and 0.11 for each milligram of carbon monoxide per cubic meter, after adjusting for meteorologic and temporal variables. Similar estimations were obtained after controlling for the autocorrelation effect by means of time series analysis. In addition, when the data were stratified by season, the effects remained in summer. This strengthened the conclusion that the relation observed in winter, spring, and throughout the study period was indeed real. After truncating the data according to sulfur dioxide or black smoke levels, the authors still found effects for these pollutants at levels below the air quality guideline of 100 micrograms/m3 established by the World Health Organization. The consistency of these results with other recent toxicologic and epidemiologic observations suggest that current air pollution standards do not totally protect public health with a margin of safety in specific places. PMID- 1877587 TI - The risk of Vibrio illness in the Florida raw oyster eating population, 1981 1988. AB - In the period 1981-1988, 333 cases of bacteriologically confirmed Vibrio illness were reported in Florida adult residents. A total of 197 patients (59.2%) had consumed raw oysters the week prior to becoming ill, and among those 197, 38 (19.3%) had a liver disease, 13 (6.6%) had past gastric surgery, and 15 (7.6%) were diabetic. To calculate a population-based incidence rate, the authors obtained prevalence estimates of annual raw oyster consumption, liver disease, previous gastric surgery, and diabetes through a random telephone survey of Florida adult residents and applied them to the January 1985 Florida population. The estimated age-standardized annual incidence of Vibrio illness per million was 95.4 for raw oyster eaters with liver disease, 9.2 for raw oyster eaters without liver disease, and 2.2 for non-raw oyster eaters. Those with prior gastric surgery had a moderately increased risk of Vibrio illness. The annual incidence for Vibrio septicemia was 82.8 for raw oyster eaters with liver disease, 2.0 for raw oyster eaters without liver disease, and 0.4 for non-raw oyster eaters. While estimates on which these data are based are subject to a number of potential biases, this is the first study to provide estimates of the risk of Vibrio illness in raw oyster eaters, and it supports the recommendation that raw oyster consumption should be avoided by persons with liver disease. PMID- 1877588 TI - Control for environmental risk factors in assessing genetic effects on disease familial aggregation. AB - A probabilistic model was developed to assess the impact of two independent dichotomous familial risk factors on familial aggregation of a disorder in pairs of relatives where one member was ascertained as a proband or index subject (i.e., a case or control). Under this model, one risk factor is of primary interest (i.e., a susceptibility gene), while the effect of the other is to be controlled (i.e., an environmental risk factor). Familial aggregation was examined within strata defined by the status of proband and relative with respect to the environmental factor. The findings suggest that for proband-relative pairs, under both the additive and multiplicative models, an environmental factor can be controlled in the analysis based solely on the status of the proband. If the relation between the genetic and environmental factors is neither additive nor multiplicative, however, the analysis must take account of environmental risk factors in both proband and relative. PMID- 1877590 TI - Re: "Depressed mood and development of cancer". PMID- 1877589 TI - Estimating the relation between dietary intake obtained from a food frequency questionnaire and true average intake. AB - Knowledge of the regression relation between dietary intake reported on a food frequency questionnaire and true average intake is useful in interpreting results from nutritional epidemiologic studies and in planning such studies. Studies which validate a questionnaire against a food record may be used to estimate this regression relation provided the food record is completed by each subject on at least two occasions. Using data collected from women aged 45-69 years during 1985 1986 in the pilot study of the Women's Health Trial, the authors show how variation in diet over time and intraindividual correlation between a questionnaire and food record obtained close together in time affects the estimation of the regression. The authors' method provides estimates of the regression slope and the questionnaire "bias" that are corrected for these effects, together with standard errors. A computer program in the SAS language, for carrying out the analysis, is provided. PMID- 1877591 TI - Re: "Predictors of sudden cardiac death among Hawaiian-Japanese men". PMID- 1877592 TI - Re: "Hyperinsulinemia and elevated blood pressure: cause, confounder, or coincidence? PMID- 1877593 TI - Temporal trends in human immunodeficiency virus type 1 seroconversion 1984-1989. A report from the Multicenter AIDS Cohort Study (MACS). AB - The 5-year temporal trends in human immunodeficiency virus type 1 (HIV-1) seroconversion between 1984 and 1989 among homosexual/bisexual men participating in the Multicenter AIDS Cohort Study (MACS) are reported. Of 3,262 initially seronegative men, 368 (11.3%) had seroconverted by December 31, 1989. Although the incidence of seroconversion declined precipitously during the first 3 years of follow-up (from 4.1% to 0.9% per 6 months), no evidence for a further substantial reduction was noted after mid-1987, since 6-month incidence rates ranged between 0.5% and 1.2%. The Chicago cohort experienced an increase in HIV-1 seroconversion during both semesters of 1989; 2.1% and 1.6% per 6 months, respectively, became newly infected. Other MACS centers did not report such an increase. Center-specific differences were observed by race; black men were at higher seroconversion risk than white men in Baltimore/Washington (relative risk (RR) = 3.4) and Chicago (RR = 2.4), while Hispanic men were at higher risk than white men in Chicago (RR = 3.3). Younger age (less than 35 years) was also associated with HIV-1 seroconversion (RR = 1.5). It is disturbing to report an overall annual seroconversion rate of 1.2% for the 2 years prior to December 31, 1989, as well as evidence for a sustained recent increase in Chicago during 1989. Long-term maintenance of safe-sex behaviors should be the cornerstone of acquired immunodeficiency syndrome prevention among homosexual/bisexual men. PMID- 1877594 TI - Occupational exposure to electromagnetic fields and breast cancer in men. AB - Data from a population-based case-control study of breast cancer in men were used to examine the hypothesis that occupational exposure to electromagnetic fields increases the risk of breast cancer. Incident cases (n = 227) diagnosed between 1983 and 1987 were obtained from 10 population-based cancer registries of the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Controls (n = 300) were selected by random digit dialing and from Medicare eligibility lists. Exposure status, defined as ever having been employed in a job which has been classified as involving potential exposure to electromagnetic fields, was assigned without knowledge of case/control status. An elevated risk was found for any job with exposure (odds ratio (OR) = 1.8, 95 percent confidence interval (CI) 1.0-3.7), and risk was highest among electricians, telephone linemen, and electric power workers (OR = 6.0, 95 percent CI 1.7-21) and radio and communications workers (OR = 2.9, 95 percent CI 0.8-10). Risk did not vary with duration of exposed employment. The risk was highest among subjects who were first employed in jobs with exposure before the age of 30 years and who were initially exposed at least 30 years prior to diagnosis. These results lend support to the theory that electromagnetic fields may be related to breast cancer in men. The hypothesis warrants evaluation in women. PMID- 1877595 TI - Comparability of data obtained from farmers and surrogate respondents on use of agricultural pesticides. AB - Information from surrogates is increasingly being used in case-control studies to evaluate cancer risks from pesticides; however, little is known about the quality of this type of information. To address this concern, the authors compared interview data collected in 1987 from 95 male Iowa farmers and their wives or other surrogates on the use of specific agricultural pesticides. Agreement between direct and surrogate interviews was excellent (83-100%) for responses to dichotomous (yes/no) questions regarding past agricultural use of specific pesticides. Although there were more discrepancies for detailed questions (e.g., the number of days per year on which each pesticide was handled), responses from spouses appear to be adequate for epidemiologic studies of pesticides and cancer. PMID- 1877596 TI - Serum micronutrients and risk of cancers of low incidence in Finland. AB - The associations between serum alpha-tocopherol, beta-carotene, retinol, retinol binding protein, and selenium levels and the subsequent occurrence of different cancers of low incidence were investigated in a nested case-control study of 39,268 men and women participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey in Finland. During follow-up from the baseline in 1968-1972 to the end of 1977, a total of 115 cancers of the lip, oral cavity, pharynx, larynx, esophagus, liver, gallbladder, kidney, urinary bladder, brain, and skin were reported to the nationwide Finnish Cancer Registry. Alpha tocopherol, beta-carotene, retinol, retinol-binding protein, and selenium concentrations were determined from stored serum samples collected from these cancer cases and matched controls at baseline. Several sites indicated an elevated risk of cancer at low levels of the serum variables, although only a few of these associations were statistically significant. Only melanoma patients had significantly lower serum alpha-tocopherol and beta-carotene levels than corresponding controls. Since the numbers of cancer cases were small, no firm conclusions can be drawn from these results until they have been confirmed in studies based on larger cohorts or on pooled data from several small samples. PMID- 1877597 TI - Tubal sterilization, hysterectomy, and the subsequent occurrence of epithelial ovarian cancer. AB - Several hypotheses predict that tubal sterilization and hysterectomy may influence a woman's risk of developing ovarian cancer. To examine the relation between these surgeries and epithelial ovarian cancer, the authors analyzed data from the Cancer and Steroid Hormone Study, a case-control study of women aged 20 54 years. Eight population-based cancer registries in the United States identified women with newly diagnosed epithelial ovarian cancer during 1980-1982 (n = 494). A comparison sample of female residents of these eight areas (n = 4,238) was identified through random digit dialing. Women who had had tubal sterilization (relative risk (RR) = 0.69, 95% confidence interval (Cl) 0.50 0.95), a hysterectomy only (RR = 0.55, 95% Cl 0.38-0.81), or a hysterectomy with unilateral oophorectomy (RR = 0.60, 95% Cl 0.31-1.17) had lower risks of ovarian cancer than did women who had never had any sterilization surgery. However, the negative associations with tubal sterilization and hysterectomy only appeared to wane after two decades. These findings may be partly explained by the screening for occult ovarian pathology that often accompanies pelvic surgery: Women whose ovaries screen as "negative" may be temporarily at low risk of being diagnosed with ovarian cancer. However, because the decreased risks persisted for so long, it is conceivable that hormonal, mechanical, or circulatory sequelae of these sterilization procedures may act to lower ovarian cancer risk. PMID- 1877598 TI - Blood pressure in Mexican Americans, whites, and blacks. The Second National Health and Nutrition Examination Survey and the Hispanic Health and Nutrition Examination Survey. AB - Previous studies of Mexican Americans have shown mean diastolic and systolic blood pressures and prevalence rates of hypertension which are either lower than or similar to those for non-Hispanic whites despite the predominance of obesity in Mexican Americans. However, those results are based on restricted samples from California and Texas. Using data from the Second National Health and Nutrition Examination Survey (1976-1980) and the Hispanic Health and Nutrition Examination Survey (1982-1984), the authors examined ethnic differences in blood pressure and hypertension. Regression analyses, stratified by sex, were used to compare mean blood pressures and rates of hypertension in Mexican Americans with those for whites and blacks. Mean diastolic and systolic blood pressures, as well as the prevalence of hypertension, were lower in Mexican Americans than in non-Hispanic whites or in blacks, with whom they shared a remarkably similar risk profile. This effect was unchanged after adjustment for age, body mass index (weight (kg)/height (cm)2 x 100), and education, indicating that blood pressure differences between Mexican Americans, whites, and blacks were not explained by the established correlates of high blood pressure. There are several possible reasons for lower blood pressure in Mexican Americans, including genetic, life style, and cultural factors. PMID- 1877599 TI - The Hypertension Prevention Trial: assessment of the quality of blood pressure measurements. AB - Blood pressure variability is an important consideration in hypertension trials for determining required sample size and consequently making accurate outcome statements. The Hypertension Prevention Trial was a randomized controlled trial carried out in 1983-1986 in four US clinics on men and women with high normal diastolic blood pressure. This trial provided an opportunity to assess conditions affecting blood pressure measurement variability. Trained blood pressure observers measured systolic and diastolic blood pressures twice, 30 seconds apart, using a random-zero sphygmomanometer. The quality of blood pressure measurements was assessed by computing the variability of the two readings per participant-visit for each blood pressure observer at each study clinic. Other sources of variability investigated included observer digit preference, time of day, and ambient temperature. On the basis of data from this population, it is estimated that the standard deviation of blood pressure values can be reduced by 5% by taking two measurements per participant-visit. An additional reduction of variability can be effected by having the duplicate blood pressure measurements made by different blood pressure observers. In special instances where the range of blood pressure values is very restricted, use of the random-zero sphygmomanometer can increase or decrease the among-participant variability in blood pressure values, depending upon where the distribution of blood pressure values is centered. PMID- 1877600 TI - White-black differences in cardiovascular malformations in infancy and socioeconomic factors. The Baltimore-Washington Infant Study Group. AB - Cardiovascular malformations were examined for white/black variation in the Baltimore-Washington Infant Study. In this population-based case-control study, cases (n = 2,087) were live births with cardiovascular malformations ascertained through pediatric cardiology centers and 53 hospitals in Maryland, the District of Columbia, and northern Virginia between 1981 and 1987. Controls (n = 2,721) were a random sample of infants from the live-birth cohort that gave rise to the cases. The proportion of infants that were white was similar for all cases as a group and controls (0.68 and 0.67, respectively). Subgroup analysis, however, revealed an excess of white infants among cases with Ebstein's anomaly (odds ratio (OR) = 3.7, 95% confidence interval (Cl) 1.1-12.5), aortic stenosis (OR = 3.6, 95% Cl 1.7-7.6), pulmonary atresia (OR = 2.5, 95% Cl 1.0-6.1), coarctation of the aorta (OR = 2.2, 95% Cl 1.4-3.5), and D-transposition of the great arteries (OR = 1.6, 95% Cl 1.1-2.5), and a deficit of white infants among cases with pulmonary stenosis (OR = 0.6, 95% Cl 0.4-0.8) and heterotaxia (OR = 0.4, 95% Cl 0.3-0.8). These associations remained when cases were stratified by infant's age or by method of diagnosis. Controlling for socioeconomic factors attenuated the white excess for Ebstein's anomaly (OR = 3.0, 95% Cl 0.9-10.5), disclosed a white excess among cases of L-transposition of the great arteries (OR = 2.8, 95% Cl 1.0-8.0), and revealed that the white excess for aortic stenosis was limited to low and middle socioeconomic strata. These results highlight racial variations in cardiovascular malformations, suggest that socioeconomic factors account for some of this variation, and identify malformation subgroups for which further evaluation of sociocultural, environmental, and familial factors is needed. PMID- 1877601 TI - Risk of death from Alzheimer's disease in a community population of older persons. AB - A random sample of 467 persons over age 65 years from the population of an urban US community, stratified by age, sex, and performance on a brief memory test, underwent clinical evaluation for dementing illness in 1982-1984. Of these persons, 134 had probable Alzheimer's disease, 166 had possible Alzheimer's disease, and 167 had no evidence of Alzheimer's disease. Over a median follow-up period of 4.9 years following evaluation, 165 (35%) died. Overall, persons with probable Alzheimer's disease had a relative risk of death 1.44 (95% confidence interval (Cl) 1.05-1.96) times that of the unaffected. Level of cognitive impairment and the presence of cachexia upon physical examination both strongly and independently modified risk of death. Among those with probable Alzheimer's disease, mortality for those with mild or moderate cognitive impairment and no evidence of cachexia was comparable to that of the unaffected. However, among those with probable Alzheimer's disease and either severe cognitive impairment or cachexia, the risk of death was substantially higher. Persons with probable Alzheimer's disease who had both severe cognitive impairment and clear cachexia had a risk of death 4.60 (95% Cl 1.63-13.1) times that of unaffected persons. PMID- 1877602 TI - Randomized recruitment in case-control studies. AB - A new sampling approach for case-control studies offers a flexible alternative to frequency matching. In the "randomized recruitment" method, subjects are individually randomized to be recruited or not on the basis of investigator imposed recruitment probabilities that can depend on both disease status and values of covariates already available or ascertained in a screening interview. When there is prior information about the odds ratios associated with the screening variables, such a design can achieve "probability matching," without the well-known disadvantages that encumber traditional matching. The method can also be used to enlarge the relative size of subsamples of interest. Following randomized recruitment, a modified logistic regression analysis allows unbiased estimation of effects associated with all variables studied, including the "matching" variables. One can also readily fit an additive model. The method is illustrated by developing the recruitment probabilities required for probability matching on age, sex, and cigarette smoking status in an ongoing study of lung cancer and exposure to radon progeny in which smoking cases are undersampled. PMID- 1877603 TI - Blind assignment of exposure does not always prevent differential misclassification. AB - The authors argue that one can never be certain whether an exposure variable which is measured with error is subject to differential misclassification in either a case-control study or a cohort study. They present hypothetic examples that demonstrate that even when misclassification is nondifferential in a 2 x 3 table, the observed odds ratios in the 2 x 2 table created by collapsing over two exposure levels can be either in the opposite direction from or more extreme than the odds ratio that would be obtained if exposures were classified correctly. The anomalies are explained by the observation that the 2 x 2 tables exhibit differential misclassification. In general, collapsing over categories which have different risks of disease and different probabilities of exposure misclassification can induce differential misclassification and even nonconservative estimates of relative risk. Collapsing of exposure levels can occur in the analysis or at the exposure assessment stage. Since indistinguishable categories can be collapsed implicitly, blind assessment of exposure, i.e., assignment without knowledge of disease status, does not guarantee that misclassification is nondifferential. PMID- 1877604 TI - Re: "Does nondifferential misclassification of exposure always bias a true effect toward the null value?". PMID- 1877605 TI - Re: "Associations are not effects". PMID- 1877606 TI - Foreword: the human genome initiative: genetics' lightning rod. PMID- 1877607 TI - Patents for critical pharmaceuticals: the AZT case. AB - Patents and other statutory types of market protections are used in the United States to promote scientific research and innovation. This incentive is especially important in research intensive fields such as the pharmaceutical industry. Unfortunately, these same protections often result in higher monopoly pricing once a successful product is brought to market. Usually this consequence is viewed as the necessary evil of an incentive system that encourages costly research and development by promising large rewards to the successful inventor. However, in the case of the AIDS drug Zidovudine (AZT), the high prices charged by the pharmaceutical company owning the drug have led to public outcry and a re examination of government incentive systems. This Note traces the evolution of these incentive programs--the patent system, and, to a lesser extent, the orphan drug program--and details the conflicting interests involved in their development. It then demonstrates how the AZT problem brings the interest of providing inventors with incentives for risky innovative efforts into a sharp collision with the ultimate goal of such systems: ensuring that the public has access to the resulting products at a reasonable price. Finally, the Note describes how Congress and the courts have attempted to resolve these problems in the past, and how they might best try to solve the AZT problem in the near future. PMID- 1877608 TI - Prenatal genetic testing and screening: constructing needs and reinforcing inequities. AB - This Article considers the influence and implications of the application of genetic technologies to definitions of disease and to the treatment of illness. The concept of "geneticization" is introduced to emphasize the dominant discourse in today's stories of health and disease and the social construction of biological phenomenon is described. The reassurance, choice and control supposedly provided by prenatal genetic testing and screening are critically examined, and their role in constructing the need for such technology is addressed. Using the stories told about prenatal diagnosis as a focus, the consequences of a genetic perspective for and on women and their health care needs are explored. PMID- 1877609 TI - Rehabilitation Act--choice of law--Glanz v. Vernick. PMID- 1877610 TI - Classify and control: genetic information in the schools. AB - Recent advances in molecular and behavioral genetics are providing theoretical models to explain complex behavior--learning disabilities and behavioral problems -in simple biological terms. There are intrinsic difficulties in interpreting genetic information. Yet genetic explanations are particularly appealing in school systems pressed by demands for efficiency and accountability. Thus, genetic explanations are affecting the way children are categorized in the schools. This Article reviews genetic advances bearing on educational issues and their implementation through biological tests. It suggests the social consequences and legal implications of the growing prevalence of genetic assumptions. PMID- 1877611 TI - Confidentiality of genetic information in the workplace. AB - This Article analyzes existing legal protections for the confidentiality of information collected through genetic screening or genetic monitoring in the workplace. It notes that there are a variety of protections, such as ethical codes for occupational physicians, statutes protecting health care information in the hands of the employers, and tort, contract and constitutional principles. It describes defenses to suits based on improper disclosure of medical information. The Article then analyzes legal bases for employee and third party access to the employee's genetic information. In response to gaps in existing legal protections, it suggests parameters for a model law protecting the confidentiality of genetic information collected in the workplace. PMID- 1877612 TI - Congenital myopathy with oculo-facial abnormalities (Marden-Walker syndrome). AB - Marden-Walker syndrome present in the neonatal period is characterized by oculo facial abnormalities, congenital myopathy, and contractures. A newborn infant with a similar pattern of anomalies is reported, and further evidence for autosomal recessive inheritance as well as new neuropathological findings are included. PMID- 1877613 TI - Familial occurrence of esophageal atresia with and without tracheoesophagel fistula: report of two unusual kindreds. AB - We describe 2 unique kindreds with familial occurrence of esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) and reviewed the literature on familial EA +/- TEF. EA +/- TEF appears to be causally heterogeneous with evidence pointing to the existence of non-genetic developmental and multifactorial forms. The literature suggests that the parents of a single affected child should be given an empiric recurrent risk between 1/2 and 2%, rising to 20% if more than one sib is affected. The empiric risk of an affected child born to an affected parent is 3-4%. Empiric risk figures are useful in counseling families at the present time; however, the 2 kindreds presented here raise the possibility of autosomal dominant transmission in certain families. A third generation of affected offspring, or additional family reports should help to clarify this issue in the future. PMID- 1877614 TI - Statistical approaches for the detection of heterozygotes for biotinidase deficiency. AB - We applied and evaluated 3 statistical approaches for the detection of heterozygotes for biotinidase deficiency in a randomly selected population of French adults. The first method, which used a cutoff value to dichotomize the population, lacked sensitivity. The second approach calculated the probability of heterozygosity for a given enzyme activity through the application of Bayes theorem to the normal density functions of the enzyme distributions of the obligate heterozygote and the test populations. A priori values of the means and standard deviations (SDs) of the genotypic distributions were used. This method was sufficiently sensitive for both population screening and genetic counseling, but requires prior knowledge of the frequency of the deficient gene (q). The third approach was similar to the second, however, maximum likelihood estimates of the means and SDs of the genotypic distributions were calculated and used to determine the probability of heterozygosity for a given enzyme activity. This method was as sensitive as the second method and is appropriate for screening populations for which there is little prior information about the gene frequency and the genotypic distributions. This method can also be used to estimate the gene frequency of the disorder within a given ethnic or racial population. Using this method, we estimated the frequency of heterozygotes (2pq) in the French population to be 0.012, which was similar to that estimated from the results of neonatal screening for biotinidase deficiency. These methods can be used to detect heterozygotes and to estimate the gene frequency of other inherited enzyme deficiencies. PMID- 1877615 TI - Phenotypic and phoniatric findings in mosaic cri du chat syndrome. AB - We report on mosaic 46,XY/46,XY,del(5)(p15) cri du chat syndrome. The clinical findings are compared with those compiled from a literature survey. A phoniatric evaluation was performed and compared with that of a cri du chat patient without mosaicism previously observed by the authors. PMID- 1877616 TI - Complementation by two non-homologous recombinant chromosomes 3. AB - The first example known to us of complementation by two non-homologous chromosomes 3 is present in the karyotype of a phenotypically normal brother of an inv(3)(p25q21) carrier. The normal chromosomes 3 are replaced by two complementary recombinant chromosomes 3. The longer recombinant duplicates 3q21 qter and is deficient for 3p25-pter. It is identical to the recombinant inherited by infants born with multiple congenital anomalies to inv(3)(p25q21) carriers. The shorter recombinant duplicates 3p25-pter and is deficient for 3q21-qter. This recombinant has previously been observed only in prometaphase spreads from sperm of an inv(3) carrier from the same kindred. Theoretically it is possible for the carrier of these complementary recombinant chromosomes 3 to produce sperm carrying either a normal 3, or the inversion 3, which could then fertilize an egg carrying a normal 3 followed by normal fetal development. However, the spouse of our propositus reported one first trimester spontaneous abortion, followed by no recognized pregnancy over the next 12 years of marriage. PMID- 1877617 TI - PI polymorphism in Israel: report on six Jewish population groups. AB - A total of 1148 Israeli Jews was typed for PI and divided by areas of origin into six groups: Eastern Europe (n = 236), Central Europe (n = 156), Rumania (n = 158), Bulgaria (n = 215), North Africa (n = 229), and Middle East (n = 154). Frequencies of PI*M1 (0.74-0.77) in Jews of European countries were higher than 0.68 in Jews of N. Africa and 0.62 in Jews of the Middle East. PI*M2 frequencies were correspondingly lower in European Jews: 0.11-0.14 vs 0.19 and 0.20 in non European Jews. PI*M3 frequency range was 0.07-0.11 in European Jews and was highest in Middle Eastern Jews (0.17). PI*Z was found in one MZ individual. PI*S was low (less than 0.01) except in Sephardi Jews of Bulgaria and N. Africa (0.016 and 0.015). A rare variant, PI*Elemberg, was observed in five individuals from different countries of origin. The present results are in accord with those of a previous study on some Israeli Jewish groups and on some other Middle Eastern groups. PMID- 1877618 TI - Ullrich-Turner syndrome in mother and daughter: prenatal diagnosis of a 46,X,del(X)(p21) offspring from a 45,X mother with low-level mosaicism for the del(X)(p21) in one ovary. AB - A woman with Ullrich-Turner syndrome but with normal secondary sex characteristics became pregnant on two occasions (ages 23 and 24). She had a 45,X karyotype in 100/100 lymphocytes and 50/50 skin fibroblasts. The first pregnancy ended in a miscarriage at 2 months of gestation. In the second pregnancy cultured amniocytes showed a 46,X,del(X)(p21) karyotype. This pregnancy resulted in an apparently normal girl. Biopsies of the mother's ovaries were obtained at the time of cesarean section. Grossly the ovaries appeared normal, and histologically the number of primordial follicles appeared normal. In the right ovary, 5/100 cells were 46,X,del(X)(p21), while all 100 cells in the left ovary were 45,X. PMID- 1877619 TI - Ectrodactyly of hands and feet in a child with a complex translocation including 7q21.2. AB - A three-way translocation involving a break point of 7q21.2 was found in a boy with tetramelic ectrodactyly. PMID- 1877620 TI - Interstitial tandem direct duplication of the long arm of chromosome 4 (q23-q27) and possible assignment of the structural gene encoding human aspartylglucosaminidase to this segment. AB - We report on a girl with a previously undescribed de novo direct tandem duplication 4q involving the segment q23----q27. Clinical manifestations included postnatal growth and psychomotor retardation, microcephaly, hirsute forehead, epicanthic folds, strabismus, depressed nasal bridge, long philtrum, small mouth, tetralogy of Fallot, and sacral dimple. Her phenotype is compared with that of previously reported cases of duplication 4q. An increased activity of the enzyme aspartylglucosaminidase (AGA) in cultured fibroblasts was demonstrated. This suggests possible assignment of the AGA gene to the chromosomal segment 4q23--- 4q27. PMID- 1877621 TI - Mouse major histocompatibility complex and lung development: haplotype variation, H-2 immunolocalization, and progressive maturation. AB - The association of the mouse major histocompatibility complex (H-2), lung maturation, and corticosteroid responsiveness has recently been demonstrated in congenic B10 (H-2b) and B10.A (H-2a) mice (Hu et al.: American Journal of Medical Genetics 35:126-131, 1990). We have investigated additional haplotypes [B10.BR (H 2k) and B10.D2 (H-2d)] to confirm that there is a strong association between H-2 haplotype variation and the degree of pulmonary maturation. Lungs of B10.D2, B10.BR, B10, and B10.A congenic mice achieve haplotypic specific maturation: B10.D2 lungs greater than B10 lungs = B10.BR lung greater than B10.A lungs. It appears that the expression of these developmental potentials is under corticosteroid regulation. Further, to test the hypothesis that H-2 antigens would be expressed earlier in embryonic lungs with the H-2b (B10) or H-2k (B10.BR) haplotype than with the H-2a (B10.A) haplotype, we investigated the spatiotemporal patterns of H-2 antigen localization in B10, B10.BR, and B10.A congenic mouse strains with and without corticosteroid treatment. The spatial patterns of H-2 antigen localization was similar in the B10, B10.BR, and B10.A mouse lungs; however, these patterns appeared earlier in both untreated and treated B10 and B10.BR mice as compared with untreated B10.A mice, suggesting an H-2 haplotype associated rate of pulmonary maturation. Following corticosteroid treatment, all congenic strains had a temporally comparable spatial distribution of H-2 antigens. Our results provide preliminary evidence suggesting that both a lung "developmental gene(s)" and a "glucocorticoid responsiveness gene(s)" are most likely outside the K-D subregions of the H-2 complex. A model of the H-2 regulation of lung maturation and corticosteroid responsiveness is discussed. PMID- 1877622 TI - Apparent association of mental retardation and specific patterns of deletions screened with probes cf56a and cf23a in Duchenne muscular dystrophy. AB - A total of 162 Duchenne (DMD) patients and two girls with a DMD phenotype were analysed for deletions in the central region of the dystrophin gene in order to determine if there was a correlation between mental retardation (MR) and the pattern of deletion. Approximately 43% of the patients studied had deletions with two dystrophin cDNAs, cf23a and cf56a, and among 148 patients who were mentally assessed, 50% were mentally retarded. The average IQ in the group of patients with DNA deletions did not differ significantly from those patients with no detectable deletions. However, six unrelated DMD boys with MR showed an identical pattern of deletion. Our observations in the group of patients who had detected DNA deletions suggest that exon 52 of the dystrophin gene may be functionally significant in the manifestation of MR: 70% (19/27) of patients with a deletion of this exon were mentally retarded, whereas only 38% (15/39) of MR patients had deletions not involving exon 52. This difference was statistically significant. PMID- 1877623 TI - Biochemical and clinical characterization of prealbuminCHICAGO: an apparently benign variant of serum prealbumin (transthyretin) discovered with high resolution two-dimensional electrophoresis. AB - We report identification, biochemical, clinical, and genetic studies of an apparently benign, electrophoretic variant of serum prealbumin (PALB, transthyretin, TTR) in a North American kindred of Swedish ancestry. The variant polypeptide stems from a C to T point mutation in exon 4 which results in methionine instead of threonine at position 119 of the mature molecule. It was discovered incidentally in a girl with classic alpha-1-anti-trypsin (A1AT) deficiency and her father during diagnostic A1AT phenotyping by ISO-DALT high resolution two-dimensional electrophoresis (2DE). Twelve relatives in the four generation paternal kindred, including five individuals who were heterozygous for the variant prealbumin, were studied. In each of these five heterozygotes, the variant allele product was equimolar and isoelectric with the normal protein, yet migrated with an apparently lower mass in the SDS-PAGE dimension. The inheritance pattern was consistent with autosomal dominant transmission. Histories and physical examinations showed no evidence of amyloidosis, as has been observed with other variants of prealbumin. Mean values of serum prealbumin and retinol binding protein levels were higher in the carriers as compared to the normal relatives in the family, but the difference was not statistically significant. Thyroid hormone levels and distribution of thyroxine and triiodothyronine among binding proteins in serum were within reference limits. Four members of the lineage had dominant, scalp-restricted keratinaceous cysts, yet only three of these four individuals had the variant. We counseled the family that this is likely a benign variant with regard to amyloidosis-related morbidity or shortened life span, although senile effects cannot be entirely ruled out. The provisional designation assigned to this allele is PALBCHICAGO. The substitution of methionine at position 119, as predicted by the DNA sequence, was confirmed by amino acid sequencing of CNBr and tryptic peptides. This substitution occurs at a CpG dinucleotide that may be a point mutational "hot spot," as has been postulated for the methionine-30 and isoleucine-122 PALB variants. The apparently lower mass of the variant probably results from a more compact conformation in SDS. With the exception of histidine-58, a charge substitution, all other amyloidosis-related prealbumin variant polypeptides had normal mobility in the ISO-DALT 2DE system. PMID- 1877624 TI - Acardiac amorphous twin with prune belly sequence in the co-twin. AB - We describe a twin with acardia acephalus or "Twin Reversed Arterial Perfusion Sequence" and prune belly sequence in the co-twin. In a former quite similar case a prune belly appearance of the co-twin of an acardiac fetus was found to be secondary to the ascites caused by cardiac failure. In the present case, we are dealing with the prune belly sequence as a separate condition, given the fact there were no signs of ascites or cardiac failure. We also found associated anomalies: agenesis of the left ureter and kidney, dysplastic right kidney and anal atresia. Urinary tract obstruction has never been described in the co-twin of an acardiac amorphous fetus. PMID- 1877625 TI - Prenatal sonographic documentation of cystic hygroma regression in Noonan syndrome. AB - Prenatal diagnosis of a posterior nuchal cystic hygroma was made at 13 weeks of gestation in a fetus diagnosed at birth with Noonan syndrome. Through serial sonographic evaluation during pregnancy, the embryologic evolution of cystic hygroma into nuchal skin thickening was appreciated and later correlated with postnatal findings of nuchal skin fold redundancy and pterygium colli in a patient with Noonan syndrome. These observations support the concept of the jugular lymphatic disruption sequence as pathogenesis of the nuchal findings in severely affected Noonan syndrome patients. PMID- 1877626 TI - Molecular analysis of Gaucher disease in a Vietnamese-Czechoslovak patient with high residual glucocerebrosidase activity. AB - A Vietnamese-Czechoslovak type 1 Gaucher disease patient with mild hematological complications was found to have approximately 20% of the normal level of fibroblast glucocerebrosidase activity. Using primers that recognize exon 9 sequences of the glucocerebrosidase structural gene absent in the pseudogene, genomic DNA sequences flanking exons 9 and 10 of the glucocerebrosidase structural gene were amplified by the polymerase chain reaction. Allele-specific oligonucleotide hybridization to amplified genomic DNA sequence of exons 9 and 10 showed an A----G transition in exon 9 that resulted in the 370Ser----370Asp substitution in one of the alleles. In the other allele, a T----C transition in exon 10 resulted in the 444Leu----444Pro substitution, creating a NciI cleavage site. The heterozygote status of the patient's parents was confirmed biochemically by the detection of intermediate levels (42-55% of normal) of fibroblast glucocerebrosidase activity. Allele-specific oligonucleotide hybridization to amplified parental genomic DNA showed that the exon 9 mutation was present in the Czechoslovak father, whereas the exon 10 mutation was inherited from the patient's Vietnamese mother. This is the first report of the exon 10 mutation in a person of Vietnamese origin. PMID- 1877627 TI - Sex identification by polymerase chain reaction using X-Y homologous primer. AB - A method of sex identification using the polymerase chain reaction technique is described. Using a pair of nucleotide primers from an X-Y homologous region, both the X and the Y sequences can be amplified simultaneously, and more importantly, they result in fragments of different lengths. The success of the procedure is therefore monitored by the presence of a X-specific band while sex is identified by the presence or absence of a Y-specific band. PMID- 1877628 TI - New X-linked syndrome of mental retardation, short stature, and hypertelorism. AB - We present a three-generation family with five retarded, abnormally appearing males and two abnormally appearing females (presumably manifesting carriers). The phenotype of the patients is different from that of all other previously described types of X-linked mental retardation (XLMR). The patients had prominent forehead, frontal bossing, hypertelorism, broad nasal tip, and anteverted nares. Chromosomes were normal including fragile X analysis. Skeletal roentgenograms were normal. PMID- 1877629 TI - Genetic epidemiology of hereditary motor sensory neuropathies (type I). AB - Patients affected with hereditary motor sensory neuropathy (HMNS) type I were traced through hospital records. Each case was re-examined, a family history was drawn, and EMG examination was performed in those members of the family who could have inherited the trait. In the prevalence year 1987, in a population of 1,067,130 inhabitants of 2 contiguous provinces of northeast Italy, 100 living cases were recorded in 30 families, giving a minimal prevalence rate estimate of 9.37/100,000. HMSN I is inherited as an autosomal dominant trait, when clinical evaluation includes EMG. No difference may be established clinically between the 2 subtypes (Ia, linked to chromosome 1 and Ib, linked to chromosome 17). Sporadic cases are very rare and the mutation rate, including both the subtypes, is estimated between 3 and 6 X 10(-6). PMID- 1877630 TI - Renal tubular dysgenesis and very large cranial fontanels in a family with acrocephalosyndactyly S.C. type. AB - We describe the first case of renal tubular dysgenesis in a newborn female who survived 15 days. The immunohistochemical and lectin binding studies confirmed the lack of proximal tubule differentiation. Electron microscopy showed undifferentiated tubular epithelium. Widely patent cranial fontanels were present in the proposita. The father and sister showed acrocephalosyndactyly Saethre Chotzen type. The parents were not related and there was no familial history of renal pathology. PMID- 1877631 TI - Angular homeostasis VII: non-monotonic correction systems. AB - We extend our model of angular homeostasis to correction functions that have a single maximum at a discrepant angle less than pi radians. We find that there are stable, and asymptotically stable, solutions that in general consist of self intersecting curves. We investigate conditions for these curves to be periodic, and describe their symmetries. One typical pattern of such a closed curve involves a finite number of loops, each having a reflection axis of symmetry, with the complete curve having a cyclic rotation group. These bear a close resemblance to patterns found in lobulated biological structures (such as the petals of a flower or the primitive fetal hand). We further discuss implications for morphogenesis. PMID- 1877632 TI - On the genetic imprinting suggested in Angelman syndrome. PMID- 1877633 TI - Diaphragmatic hernia and epidermolysis bullosa in two sibs. PMID- 1877634 TI - Postaxial polydactyly as heterozygote manifestation in Ellis-Van Creveld syndrome? PMID- 1877635 TI - Occupational therapy: an endangered species or an academic discipline in the 21st century? PMID- 1877636 TI - The contribution of motor skills and playfulness to the play performance of preschoolers. AB - Consideration of a child's motor proficiency, intrinsic motivation, internal locus of control, and freedom to suspend many of the constraints of objective reality were proposed to provide a more comprehensive assessment of play than would an assessment of play performance alone. For empirical validation of this conceptual model of play, 29 subjects (15 nondisabled children and 14 children with juvenile rheumatoid arthritis) between the ages of 4 years 6 months and 6 years 6 months were given four assessments: (a) the Preschool Play Scale (Bledsoe & Shepherd, 1982, Knox, 1974); (b) the Bruininks-Oseretsky Test of Motor Proficiency (Bruininks, 1978); (c) the Preschool and Primary Internal-External Locus of Control Scale (Nowicki & Duke, 1974); and (d) tests of associative fluency (Wallach & Koogan, 1965; Ward, 1968). Multiple regression procedures revealed that, when considered together, scores on the Bruininks-Oseretsky Test of Motor Proficiency, tests of associative fluency, and the Preschool and Primary Internal-External Locus of Control Scale predicted scores on the Preschool Play Scale, thereby supporting the usefulness of the proposed theoretical model. Further, there was no significant difference in the mean scores of the two groups on the Preschool Play Scale. Although this finding may be an artifact of the small sample size, it also may support the authors' belief that children with motor impairments are able to compensate for their limitations by developing areas of relative strength that allow them to play normally. When this belief was further tested with Pearson product-moment correlations and Fisher's Z transformations, it was found that correlations between the test scores of the nondisabled children were not significantly different from those of the children with juvenile rheumatoid arthritis. Clearly, further research is needed. PMID- 1877637 TI - Ventilatory and cardiometabolic responses to unilateral sanding in elderly women with ischemic heart disease: a pilot study. AB - This study was undertaken to investigate how 8 elderly women with ischemic heart disease would respond to a unilateral sanding activity. Three ventilatory measures-expiratory tidal volume, respiratory rate, and expiratory volume--and four cardiometabolic measures--metabolic equivalent, systolic blood pressure, heart rate, and pressure rate product--were continuously recorded during the sanding activity. The two independent variables were angle of the sanding board and sanding velocity. The activity was graded to yield five conditions: (a) sitting at rest; (b) 0 degrees at 15 cycles per min (cpm); (c) 0 degrees at 30 cpm; (d) 15 degrees at 15 cpm; and (e) 15 degrees at 30 cpm. The findings indicated that increasing the angle of the board while holding the velocity constant did not always increase the mean values of the ventilatory and cardiometabolic measures. However, increasing the velocity while holding the angle constant always increased the mean values of the dependent variables. The data also indicated that the metabolic equivalent reached during the sanding activity was no greater than 2, which corresponds to a light activity, such as playing a musical instrument. Replication of the study with a larger sample size may further elucidate the behavior of these two functions during a graded sanding activity. In the present study, a unilateral sanding activity by elderly patients with cardiac impairment was shown to provide valuable data on ventilatory and cardiometabolic functions. The study also demonstrated that a unilateral sanding activity can be safely used as a graded activity in occupational therapy for the cardiac rehabilitation of elderly women. PMID- 1877638 TI - Comparison of pencil-grip patterns in first graders with good and poor writing skills. AB - The purpose of this study was to compare nondysfunctional children with and without handwriting difficulties for an examination of grip and hand preference. Additionally, in the group of children with handwriting difficulties, the children with decreased proprioceptive-kinesthetic finger awareness were compared with the children without such a decrease. The results suggest that children with handwriting difficulties may demonstrate a lower grip score than children without handwriting problems. In addition, among children with poor handwriting, those with decreased proprioceptive-kinesthetic finger awareness may demonstrate a lower grip score than those with good proprioceptive-kinesthetic awareness. Children with poor hand-writing also show less hand preference than those with good handwriting. PMID- 1877640 TI - The use of technical aids among community-based elderly. AB - The growing elderly population will increase the need for assistive technology in the form of technical aids and housing adaptations to facilitate independence in activities of daily living. In this study, which was undertaken to facilitate a better understanding of the life-styles of the disabled elderly and the role of technical aids, 57 disabled persons over 74 years of age were studied. All of the subjects were residents of a rural Swedish community. The subjects had a total of 422 aids, an average of 7.4 per person. Seventy-five percent of the aids were being used, and 42 persons had at least one aid that granted autonomy. This finding illustrates the importance of technical aids in home care. It is recommended, therefore, that information about assistive technology be disseminated to personnel at all levels of community-based care. PMID- 1877639 TI - Toy Control Program evaluation. AB - The Toy Control Program for the Apple IIe microcomputer is a software and hardware package developed for the training of single-switch scanning skills. The specially designed scanning programs provide on screen visual feedback and activate a battery-powered toy to reinforce performance. This study examined whether the training of preschool subjects in single-switch scanning skills with the Toy Control Program would result in increased task completion scores and increased levels of attention to task, as compared with conditions of toy activation only and microcomputer programs with screen reinforcement only. The results showed that the subjects paid significantly more attention to the toys as reinforcers (p less than .01). No significant difference was found for the performance results of the three conditions. These findings support the use of a program like the Toy Control Program, which integrates the instructional capabilities of a computer with the reinforcement potential of a toy and the creativity of a therapist. PMID- 1877641 TI - The effects of a short thumb opponens splint on hand function in cerebral palsy: a single-subject study. AB - An AB single-subject research design was used to assess the effectiveness of a short thumb opponens splint on hand function in a 4-year-old girl with cerebral palsy. Baseline data for active range of motion, grip and pinch strength, grasp patterns, the Box and Block Test of manual dexterity (Mathiowetz, Voland, Kashman, & Weber, 1985), and 1-in. cube stacking were collected twice a week for 4 weeks. The child was fitted with a short thumb opponens splint, which was worn 6 hr during the day and all night for 4 weeks. The twice-weekly measures of the dependent variables continued during the treatment phase. Visual and statistical analysis of the data indicate that the child showed a clinically significant improvement in palmar and radial abduction, thumb opposition, grip strength, performance on the Box and Block Test scores, cube stacking, and lateral pinch. These results suggest that for this child with cerebral palsy, the use of a short thumb opponens splint improved underlying aspects of hand function as well as hand function itself. Replication of this study with a more complex single subject design involving more subjects is recommended to confirm these results. PMID- 1877642 TI - Occupational therapy service: individual and collective understandings of the founders, Part 2. AB - This inquiry continues to explore the understandings of patient, therapist, and occupation held by the founders of the National Society for the Promotion of Occupational Therapy. The first part of this search, published in the April 1991 issue of AJOT, discussed personal narratives and anecdotes about George Edward Barton, Susan Elizabeth Tracy, and William Rush Dunton, Jr. This second part extends that discussion through an examination of the shaping influence of World War I on Dunton's beliefs and through consideration of the views held by Eleanor Clarke Slagle, Herbert J. Hall, Susan Cox Johnson, and Thomas Bessell Kidner. Influenced by contemporary historical forces as well as their personal experiences, the founders shared a common understanding that the right occupation could help persons in need. Personal narratives found within the early occupational therapy literature illustrate each founder's unique understanding of the manner in which occupation might address contemporary problems. Each view contributed to the development of a multifaceted therapy. Exploration of the multiple interpretations that shaped a common idea may help current therapists to better understand their heritage of caring and to compare it with current practices. PMID- 1877643 TI - Occupational therapy intervention for overuse syndrome. PMID- 1877644 TI - An assistive eye-drop mold. PMID- 1877645 TI - A system for involving patients in program planning. AB - Although standards exist that require occupational therapists and other health care professionals to include patients in the treatment planning process, our observations lead us to believe that patient involvement is not being maximized. The Patient Participation System allows therapists to actively involve patients in a systematic goal-setting process. The initial results of the use of this system indicate that patients can be effectively involved in establishing personalized, specific goals; identifying outcomes; and evaluating treatment effectiveness. PMID- 1877646 TI - Role of leukocytes in metabolic and functional derangements of experimental glomerulonephritis. AB - Nephrotoxic nephritis (NTN) is characterized by an influx of leukocytes into the glomerulus, with accompanying glomerular dysfunction and a marked increase in glomerular eicosanoid production. We examined the relationship between the glomerular inflammatory cell infiltrate and the concomitant metabolic/functional changes in this model of renal disease using a combination of in vivo immunologic strategies to both decrease [X-irradiation and cobra venom factor (CVF)] and increase (preimmunization with rabbit immunoglobulin G or accelerated NTN) the inflammatory cell infiltrate. With the use of these manipulations, a close correlation between glomerular leukocytes and the proteinuria of NTN was observed. The ablative strategies (X-irradiation and CVF) also attenuated the increase in leukotriene B4 (LTB4) generation seen with NTN and virtually completely prevented the increase in thromboxane B2 (TxB2) production (basal and angiotensin II elicited). Accelerated NTN, in contrast, increased and prolonged the rise in glomerular LTB4 production and exacerbated the increase in TxB2 production. Glomerular prostaglandin E2 production was not altered by the induction of nephritis nor any of the aforementioned immunologic manipulations. Regression analysis established that glomerular TxB2 production correlated significantly with the leukocyte influx at both 3 and 24 h. Glomerular LTB4 production correlated only with the presence of leukocytes at 3 h. Both glomerular TxB2 and LTB4 production were closely correlated with the renal dysfunction as assessed by proteinuria. These data suggest that leukocytes play a direct critical role in both the functional and metabolic alterations that occur in the setting of NTN. They further imply that leukocytes are crucial to the observed increase in glomerular eicosanoid production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877647 TI - Endothelin synthesis by rabbit renal tubule cells. AB - Endothelins regulate nephron sodium and water transport, prostaglandin E2 (PGE2) synthesis, and phospholipid metabolism. Recent studies suggest that renal tubule cells synthesize endothelins. To determine which nephron sites have such potential, endothelin production by cells derived from different nephron segments was examined. Immunoreactive endothelin 1 (ET-1) and endothelin 3 (ET-3) were measured in supernatants of cultured rabbit proximal tubule (PT), medullary thick ascending limb (MTAL), cortical collecting tubule (CCT), and inner medullary collecting duct (IMCD) cells. All cell types released immunoreactive ET-1 and ET 3. However, the amounts of endothelin produced differed as follows: IMCD greater than MTAL greater than CCT much greater than PT for ET-1 and IMCD greater than MTAL = PT = CCT for ET-3; in all cases ET-1 much greater than ET-3. To confirm de novo ET-3 synthesis, IMCD cells were labeled with [35S]cysteine, and the supernatant was immunoprecipitated with anti-ET-3 antibody. Sample and standard ET-3 eluted at identical positions on high-performance liquid chromatographs, confirming de novo synthesis of ET-3 by cultured IMCD cells. These data raise the possibility of an important functional role for nephron-derived endothelin and, in particular, endothelin produced by tubule cells in the medulla. PMID- 1877648 TI - Effects of maleic acid on renal phosphorus transport: role of dietary phosphorus. AB - The effects of maleic acid on renal phosphate (Pi) transport were examined by clearance and brush-border membrane vesicle (BBMV) transport studies. In normal rats, maleic acid 50 mg.kg body wt-1.h-1 increased the phosphaturia (P less than 0.001). Intraperitoneal administration of a similar dose of maleic acid decreased the BBMV uptake of Pi but not glucose. In rats fed a low-phosphate diet (0.03%), the maleic acid-induced phosphaturia was blunted, but the inhibitory effect on the BBMV transport of Pi persisted. In chronic parathyroidectomized rats fed a low-phosphate diet, where the filtered load of Pi was higher than in the previous groups, the phosphaturia was abolished, but the inhibition of the BBMV transport of Pi was sustained. Both the in vitro incubation of BBMVV and in vivo administration of maleic acid were associated with a competitive inhibition of Pi transport. These studies indicate that the maleic acid-induced phosphaturia is expressed at the apical membrane entry step of Pi, and the enhanced distal tubular reabsorption accounts for the lack of phosphaturia in dietary Pi deprivation. PMID- 1877649 TI - Pathogenesis of glomerular sclerosis in subtotally nephrectomized analbuminemic rats. AB - The Nagase analbuminemic rat (NAR), a mutant of the Sprague-Dawley (SD) strain, exhibits persistent hypercholesterolemia, thrombocytosis, and enhanced platelet aggregation, abnormalities possibly involved in the genesis of glomerular sclerosis (GS). Previous observations suggest that these rats never develop aging GS. We studied the development of GS in NAR after 5/6 nephrectomy (Nx). Fifteen days after Nx, marked glomerular hypertension was observed in NAR, compared with only mild elevations in SD rats. Glomerular hypertrophy was more marked in SD rats than in NAR. Enalapril normalized glomerular volume and partially reversed glomerular hypertension in NAR without altering platelet function or cholesterol levels. Glomerular endothelial injury and intraluminal fibrin deposition were seen only in NAR. Two months after Nx, severe GS and massive glomerular lipid deposition were seen in NAR, whereas only mild glomerular injury occurred in SD rats. Enalapril attenuated GS and prevented lipid deposition in NAR. Glomerular hypertension may be a key factor in the genesis of GS in this model in association with endothelial injury, intracapillary coagulation, and lipid accumulation. PMID- 1877650 TI - Indirect Na+ dependency of urate and p-aminohippurate transport in pig basolateral membrane vesicles. AB - Membrane vesicles were used to study the basolateral transport of urate and p aminohippurate (PAH) in the proximal tubule of the pig kidney. Consistent with a cooperation between a Na(+)-2-oxoglutarate cotransporter and a 2-oxoglutarate urate or a 2-oxoglutarate-PAH exchanger, urate and PAH uptakes were stimulated in presence of extravesicular 2-oxoglutarate when an inwardly directed Na+ gradient was applied. Both transports exhibited, however, different characteristics. The optimal 2-oxoglutarate concentration for stimulating uptakes was 10 microM for PAH and 150 microM for urate. Extravesicular chloride was required to observe a stimulation of PAH uptake but not of urate uptake. Transports of both PAH and urate exhibited different affinity sequences for various organic anions. Stimulated PAH uptake was inhibited by probenecid greater than cold PAH greater than urate = pyrazinoate greater than lactate, whereas stimulated urate uptake was inhibited by probenecid greater than cold urate greater than PAH and not by pyrazinoate or lactate. These results are consistent with independent transport processes for urate and PAH in pig basolateral membrane vesicles, both being indirectly driven by an inwardly directed Na+ gradient. PMID- 1877651 TI - Vasoconstrictor effect of angiotensin and vasopressin in isolated rabbit afferent arterioles. AB - The present studies were performed to examine the vasoconstrictor effect of angiotensin II (ANG II), angiotensin III (ANG III), and vasopressin in isolated afferent arterioles of the rabbit kidney. Afferent arterioles were dissected together with their glomerulus and perfused with a pressure head of 120 cmH2O. Changes in vasomotor tone were assessed as diameter changes on videotaped recordings. Afferent arterioles responded to the angiotensins and vasopressin with dose-dependent reductions in vascular diameters with half-maximum responses being observed at concentrations between 10(-9) and 10(-8) M. Responses to ANG II and III were inhibited by saralasin. Contractile responses to ANG II and vasopressin were not altered by prior occlusion of the efferent arteriole, suggesting that afferent vasoconstriction does not represent a myogenic reaction to an increase in efferent resistance. The vasoconstrictor response to ANG II was largely eliminated by removal of the glomerulus and the distal-most portion of the afferent arteriole, whereas the response to vasopressin remained intact. Our data are consistent with the notion that the juxtaglomerular apparatus (JGA) and/or glomerulus may control proximal afferent arteriolar contractility by electrotonic or myogenic coupling mechanisms or by producing cofactors that modulate vasomotor responses. PMID- 1877652 TI - Neurogenic regulation of rate of achieving sodium balance after increasing sodium intake. AB - Evidence that the renal sympathetic nerves have direct effects on renal tubular function suggests that neurogenic mechanisms may play an important role in the daily regulation of sodium balance. We evaluated the influence of the renal nerves on the rate of elevating urinary sodium excretion (UNaV) after a step increase in fixed sodium intake. Conscious rats with innervated (INN) or denervated (DNX) kidneys were placed on low-sodium intake (LNa = 0.3 meq/day) or a normal sodium intake (NNa = 1.0 meq/day) by intravenous infusion. Hourly changes in UNaV were determined 24 h before and 72 h after increasing sodium intake to either NNa or high-sodium intake (HNa = 5.0 meq/day). Switching from LNa to NNa, INN rats increased UNaV within 24 h; however, DNX rats did not begin to increase UNaV until hour 60. Cumulative sodium balance over 72 h was more positive in DNX rats (INN = 1.29 +/- 0.29 meq; DNX = 2.06 +/- 0.21 meq, P less than 0.05). During the LNa-to-HNa switch, both INN and DNX rats increased UNaV equally for 12 h; however, at this time INN rats continued to increase UNaV, whereas DNX rats did not. DNX rats had a net accumulation of 2.54 meq more sodium than INN rats over 72 h. Significant inhibition of plasma renin activity within the first 24 h occurred only in rats receiving the LNa-to-HNa switch in sodium intake, and this response was not different between rats with innervated and denervated kidneys. These data suggest that the renal nerves provide a rapid sodium excretory response to step increases in sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877653 TI - Augmented bidirectional HCO3 transport by rat distal tubules in chronic alkalosis. AB - Free-flow micropuncture studies show both augmented net HCO3 reabsorption in the distal tubule of rats with chronic metabolic alkalosis and higher HCO3 delivery to this nephron segment. The present studies in rats used in vivo microperfusion of surface distal tubules to investigate whether the augmented net reabsorption 1) was due to decreased HCO3 secretion and/or to increased proton secretion or 2) depended on the higher HCO3 delivery to the distal tubule. Artificial perfusates were designed to simulate in situ deliveries of HCO3 to the distal tubules of both alkalotic and control animals and to represent extremes of in situ Cl deliveries. Rather than being decreased, both measured and calculated HCO3 secretion were higher in the alkalotic animals for each perfusate used. Similarly, calculated proton secretion (difference between net HCO3 reabsorption and calculated HCO3 secretion) was higher for the alkalotic animals using each HCO3-containing perfusate. Augmented net HCO3 reabsorption by alkalotic animals was more clearly demonstrated using higher HCO3 deliveries and Cl-free perfusates. These studies demonstrate that both the reabsorptive and secretory components of net HCO3 transport are increased in the distal tubule of animals with chronic metabolic alkalosis. PMID- 1877654 TI - Effects of acute nitric oxide inhibition on rat glomerular microcirculation. AB - Endothelium-derived relaxing factor (EDRF), recently identified as nitric oxide (NO), has been shown to be released by glomerular endothelial cells and might influence the glomerular microcirculation. To examine this hypothesis, we studied in rats the renal effect of acute administration of NG-monomethyl-L-arginine (L NMMA), a specific inhibitor of NO synthesis. Adult male Munich-Wistar rats were studied before and after intravenous administration of either pure saline or a bolus injection of L-NMMA (20 mg) followed by a continuous infusion of the inhibitor (0.4 mg/min). Although saline alone had no effect on systemic or glomerular hemodynamics, L-NMMA promoted marked systemic hypertension, glomerular arteriolar vasoconstriction, and glomerular hypoperfusion. Since efferent resistance was disproportionately increased, glomerular hydraulic pressure was also markedly elevated. The glomerular ultrafiltration coefficient (Kf) fell to 42% of control. Single-nephron glomerular filtration rate was unaffected. Striking polyuria was also observed. These findings suggest that EDRF exerts a basal relaxing effect on the glomerular microcirculation. PMID- 1877655 TI - Opposed responses of large and small coronary arteries to propranolol during exercise in dogs. AB - This study was carried out to determine the relative role of alpha- and beta adrenoceptors at the level of large epicardial and small resistance coronary arteries when sympathetic tone is increased by exercise. The responses of left circumflex coronary diameter and blood flow were examined at rest and during treadmill exercise in seven chronically instrumented dogs during control conditions (saline) and after propranolol administration (1 mg/kg) either alone or in combination with phentolamine (1.5 mg/kg). In control conditions, graded treadmill exercise (5, 10, and 12 km/h) resulted in a progressive increase in coronary artery diameter and decrease in coronary vascular resistance. After propranolol, coronary vascular resistance slightly increased at rest and then progressively decreased during exercise. Surprisingly, coronary artery diameter significantly decreased at rest as well as throughout the exercise period. Phentolamine significantly reduced the propranolol-induced effects on coronary arterial diameter but did not restore the exercise-induced dilation of the large coronary arteries observed during control conditions. In addition, phentolamine prevented the propranolol-induced increase in coronary vascular resistance at rest and reinforced the exercise-induced decrease in coronary vascular resistance observed under propranolol. Thus beta-adrenoceptors are essential in the mediation of exercise-induced dilation of large coronary arteries. In contrast, activation of beta-adrenoceptors is only partially responsible for the decrease in coronary vascular resistance during exercise. Finally, constriction of large coronary arteries after propranolol is mainly explained by the unmasking of alpha adrenergic tone at rest, but other mechanisms are involved during exercise. PMID- 1877656 TI - Effect of blood flow rate and blood flow history on newborn pulmonary microcirculation. AB - The purpose of this study was to determine whether increased pulmonary blood flow and/or the history of pulmonary blood flow alters microvascular pressures in lungs of newborns. Using the direct micropuncture technique, we measured pressures in 20- to 60-microns-diameter arterioles and venules in isolated lungs of newborn rabbits at consecutive blood flow rates of 50 (baseline), 100, and/or 200 ml.min-1.kg-1. Then in some lungs we returned blood flow rate to baseline and repeated microvascular pressure measurements. We kept left atrial pressure the same at all blood flow rates. When blood flow rate increased and left atrial pressure was maintained constant, pulmonary arterial, 20- to 60-microns-diameter arteriolar, and 20- to 60-microns-diameter venular pressures increased such that the percentage of total pressure drop that occurred across veins increased. When we returned blood flow to baseline, venular pressure returned to baseline, but arteriolar and pulmonary arterial pressures returned to values less than baseline so that the percentage of the total pressure drop that occurred across microvessels decreased. Thus both blood flow rate and blood flow history are important determinants of the longitudinal distribution of pulmonary vascular pressures across newborn lungs. These findings also suggest that in newborn lungs venules greater than 60 microns diameter are poorly distensible such that higher blood flow rates result in increased microvascular pressures. Hence, under conditions of increased pulmonary blood flow, such as occurs with left to right shunts, the tendency for edema formation will increase in newborn lungs even if left atrial pressure does not increase. PMID- 1877657 TI - Quantitation of dynamic AV nodal properties and application to predict rate dependent AV conduction. AB - A number of functional properties of the atrioventricular (AV) node have been described in response to changes in the atrial input rate. The purpose of this study was 1) to develop quantitative descriptors of these properties, and 2) to determine whether they can account for rate-dependent changes in AV nodal conduction. The delay in AV nodal conduction of single premature beats (recovery) was found to be an exponential function of coupling interval with a time constant of 66 +/- 2 (+/- SE) ms. A single abbreviated (facilitation) cycle did not alter the time constant of recovery or basal conduction for a subsequent beat but shifted its recovery curve to the left to an extent exponentially related to the facilitation cycle length. The induction of a tachycardia with HA interval fixed so as to control the recovery and facilitation variables resulted in a first order onset of AV conduction slowing (fatigue). The fatigue process had a time constant in the range of 70 beats and a magnitude that was a decaying exponential function of HA interval. An equation incorporating quantitative descriptors of recovery, facilitation, and fatigue accurately predicted rate-dependent changes in AH interval. We conclude that 1) the AV nodal properties of recovery, facilitation, and fatigue are amenable to quantitative characterization, and 2) rate-dependent changes in AV nodal conduction time can be well described in terms of these underlying properties. PMID- 1877658 TI - Ischemia and reperfusion-induced arrhythmias in rabbits with chronic heart failure. AB - The incidence of ventricular arrhythmias occurring during acute myocardial ischemia and reperfusion was studied in anesthetized rabbits with chronic heart failure. Cardiac failure was induced by volume and pressure overload and was characterized by marked hypertrophy (84%) and lower systolic aortic blood pressure (112 +/- 3 mmHg) than in controls (124 +/- 2 mmHg, P less than 0.01). During the first 20 min postcoronary artery ligation, the incidence and duration of ventricular fibrillation were greater in the heart failure group (76% and 485 +/- 77 s, respectively) compared with the control group (27% and 86 +/- 37 s, respectively, P less than 0.01). Reperfusion-induced arrhythmias after various ischemic durations were also more frequent in the heart failure group than in the control group. Papillary muscles taken from rabbits with heart failure showed a reduced diastolic potential and a prolonged action potential duration (APD90) compared with the control group (by 7 and 46%, respectively), but there was no change in maximum upstroke velocity. The present study established that rabbits with pronounced morphological signs of chronic heart failure have an enhanced susceptibility to ischemia and reperfusion-induced arrhythmias. As already described in situations of uncomplicated cardiac hypertrophy, a delay in the repolarization process could represent an arrhythmogenic mechanism in this model. PMID- 1877659 TI - Collagen remodeling and changes in LV function during development and recovery from supraventricular tachycardia. AB - Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dYsfunction and dilatation. Termination of SVT appears to improve symptoms of congestive heart failure. However, the structural events that occur during development and regression of SVT-induced cardiomyopathy are unknown. Accordingly, LV function (simultaneous echocardiogram-catheterization) and collagen content and distribution were measured in pigs (23-25 kg) assigned to three groups: 1) rapid atrial pacing (240 beats/min) for 3 wk (SVT, n = 10); 2) SVT for 3 wk, followed by deactivation of the pacemaker and a 4-wk recovery period (PST, n = 9); and 3) sham-operated controls (CON, n = 10). LV fractional shortening was 30 +/- 2% in CON, fell to 13 +/- 2% with SVT (P less than 0.05), and returned to CON values with PST (31 +/- 2%). SVT resulted in significantly increased LV end-diastolic dimension compared with CON (4.9 +/- 0.3 vs. 3.5 +/- 0.2 cm, P less than 0.05) and no change in LV wt/body wt (2.7 +/- 0.2 vs. 2.6 +/- 0.2 g/kg, P = 0.85). Termination of SVT (PST) resulted in development of hypertrophy, LV mass increased to 3.50 +/- 0.3 g/kg (P less than 0.05 vs. CON). With the use of pressure-dimension-thickness relations during diastole, the regional chamber stiffness constant (Kc) was computed. Kc was unchanged by SVT compared with CON (5.3 +/- 1.4 vs. 3.7 +/- 0.5, P greater than 0.35) but increased with PST (7.4 +/- 0.6, P less than 0.05). LV hydroxyproline content significantly fell with SVT compared with CON (2.24 +/- 0.58 vs. 2.68 +/- 0.45 mg/g dry wt, P less than 0.05, respectively) and significantly increased with PST (3.68 +/- 0.85 mg/g dry wt, P less than 0.05). With the use of transmission electron microscopy, collagen fibril diameter was reduced with SVT compared with CON (1.45 +/- 0.5 vs. 1.7 +/- 0.5 microns, P less than 0.05) and increased with PST (3.3 +/- 1.4 microns, P less than 0.05). Scanning electron microscopy revealed disruption of collagen struts between adjacent SVT myocytes and a thickened collagen weave with PST. Thus chronic SVT resulted in systolic and diastolic dysfunction and reduced collagen support of adjoining myocytes. Early recovery from SVT was associated with LV hypertrophy, increased collagen, and increased LV stiffness. PMID- 1877660 TI - Correlation of myocardial necrosis with kinetics of 111In-labeled myosin-specific antibody in isolated rabbit septum. AB - Radiolabeled monoclonal antibody fragments to myosin, specifically 111In-labeled antimyosin, have been shown to be effective for imaging areas of myocardial infarct. To determine if 111In-labeled antimyosin can be used to assess the extent of necrosis, we compared the tissue retention fraction of 111In-labeled antimyosin with the amount of creatine kinase (CK) released from the isolated, perfused, interventricular rabbit septum after an intervention to induce tissue necrosis. 111In-labeled antimyosin was injected and tissue radioactivity was monitored for a 60-min period under control conditions. Effluent samples were also collected during this period and assayed for CK content. After a period of Ca2+ depletion followed by Ca2+ repletion, 111In-labeled antimyosin was again injected, and washout and CK data were collected. Comparison of the changes in 111In-labeled antimyosin retention fraction from control to intervention with the corresponding increase in CK released during intervention resulted in a correlation coefficient of 0.83. To corroborate the findings of the Ca2+ depletion followed by repletion experiments, further experiments were conducted in which zero-flow ischemia followed by reperfusion was used as a means of introducing necrosis in the septum. The resulting correlation coefficient between CK release and 111In-labeled antimyosin retention fraction was 0.82. The results of these experiments indicate that 111In-labeled antimyosin can be used to quantitatively estimate the extent of necrosis in the rabbit septum, as determined by CK release, and endorse the potential use of tracer kinetics in humans for quantitation of myocardial necrosis in vivo. PMID- 1877661 TI - Activated oxygen species do not mediate hypercapnia-induced cerebral vasodilation in newborn pigs. AB - In newborn pigs, vasodilation in response to hypercapnia is dependent on prostaglandin (PG) H synthase. We investigated the contribution of activated oxygen by-products to hypercapnia-induced PGH synthase-dependent dilation of pial arteries and arterioles in anesthetized newborn pigs. Activated oxygen species were generated on the cerebral surface using xanthine oxidase and hypoxanthine. Catalase, H2O2, and iron or N-(2-mercaptopropionyl)-glycine (MPG) were used to separate effects of superoxide anion and hydroxyl radical. All the activated oxygen species tested caused vasodilation of both arteries and arterioles. Vasodilation to all activated oxygen species was largely reversible with only the hydroxyl radical encouraging combination of xanthine oxidase, hypoxanthine, H2O2, and FeCl3, causing significant dilation 20 min after removal of treatment. Cotreatment with MPG blocked this residual dilation. Neither pretreatment with the extracellular superoxide anion radical scavenger, superoxide dismutase (SOD), the intracellular superoxide anion radical scavenger, Tiron, the H2O2 scavenger, catalase, nor hydroxyl radical scavengers, dimethyl sulfoxide (DMSO) and MPG, altered vasodilation of pial arteries or arterioles in response to hypercapnia. Furthermore, the increase in cerebral prostanoid synthesis in response to hypercapnia was not affected by pretreatment with SOD, Tiron, catalase, DMSO, or MPG. We conclude that the progressively reduced forms of oxygen that would be produced during PGH synthase metabolism of arachidonic acid can dilate pial arteries and arterioles of newborn pigs. However, these activated oxygen species are not responsible for the vasodilation to hypercapnia in the newborn pig, suggesting that eicosanoids cause the dilation. PMID- 1877662 TI - Effect of skin concavity on subcutaneous tissue fluid pressure. AB - We tested the hypothesis that mechanical factors associated, with a skin concavity can cause the local tissue fluid pressure to become more negative. Perforated Teflon collars, 26 mm in diameter and having various heights (5, 10, 13, and 16 mm), were implanted into the fascial plane of the inguinal and abdominal areas of six sheep. After several weeks, visible signs of edema were no longer apparent, and the skin formed a concavity within the center of each collar. The depth of each concavity was measured using an electronic micrometer, and the tissue fluid pressure beneath the concavity was measured using a needle method. Over the entire range of collar heights, the average depth of the concavities ranged from 1.1 to 4.7 mm in the abdominal tissues and from 1.8 to 5.5 mm in the inguinal tissues. The respective values of tissue fluid pressure averaged -4.6 to -13.0 and -5.7 to -12.8 mmHg. The results therefore indicate that implanting deeper collars leads to the formation of deeper concavities in the skin and also to greater negativity in the free tissue fluid pressure beneath the skin. Linear regression extrapolation to a collar height of 0 mm corresponded to a tissue fluid pressure of -1.0 mmHg in the abdominal tissue and -2.4 mmHg in the inguinal tissues. A model based on excessive pumping of the lymphatic system in the vicinity of a concavity is provided to explain this newly described phenomenon. We conclude that mechanical factors associated with the formation of a skin concavity cause or permit the tissue fluid pressure to reach levels of negativity far greater than those that exist in the absence of a concavity. PMID- 1877663 TI - NMR studies of beta-oxidation and short-chain fatty acid metabolism during recovery of reperfused hearts. AB - The effects of beta-oxidation on the contractile recovery and metabolic activity of postischemic (10 min) rabbit hearts were examined during reperfusion with the short-chain fatty acid butyrate. Hearts received either 13C-enriched butyrate or acetate to evaluate metabolic targeting with 13C nuclear magnetic resonance (NMR) spectroscopy. Acetate and butyrate supported similar contractility (rate of pressure development, dP/dt) and 31P-NMR-detected, high-energy phosphate (HEP) levels during normal perfusion. In postischemic hearts, butyrate sustained a greater percentage of preischemic dP/dt (83 +/- 4%) than did acetate reperfusion (44 +/- 6%, P less than 0.05) with no differences in HEP. The efficiency of oxygen consumption per unit of work was greater in hearts reperfused with butyrate (2.8 +/- 0.2 microM.g-1.mmHg-1) vs. acetate (3.4 +/- 0.1). Inhibition of butyrate oxidation with 4-bromocrotonic acid (4-BCA) during normal perfusion severely reduced dP/dt and HEP. Acetate supported normal dP/dt and HEP levels during perfusion with 4-BCA and butyrate, but contractile recovery during reperfusion with acetate, 4-BCA, and butyrate (46 +/- 6%) was similar to that with acetate alone. With acetate and butyrate combined at reperfusion, acetate accounted for 56% of substrate entering oxidative metabolism at acetyl CoA and delayed contractile recovery (57 +/- 5% at midpoint and 80 +/- 6% at end). Thus improved respiratory efficiency of contraction in reperfused hearts was related to the activity of beta-oxidation. PMID- 1877664 TI - Afferent vascular resistance control during hemorrhage in normal and autonomically blocked rabbits. AB - We examined the role of the arterial and cardiac baroreceptors on the hindquarter conductance and heart rate responses of conscious rabbits bled at approximately 3% blood volume (BV)/min to 80% BV (i.e., 20% BV removed). We used rabbits with both sets of baroreceptors working and when only one or neither sets was working. Each animal was studied with normal effector function and during autonomic blockade (hormonal + local effectors), where release of arginine vasopressin (AVP) and renin (angiotensin II, ANG II) were enhanced. The local response (LR) to hemorrhage was determined in a separate group of neurohumorally blocked rabbits. The estimated constrictor response (ECR) was the difference between the LR and net conductance response. In normal rabbits, the ECR was 49 units, with the estimated arterial-to-cardiac barorecptor drive ratio approximately 2.8:1 and with the two receptor groups acting by simple addition. Both barorecptors contributed to the rise in heart rate, with the relative arterial-to-cardiac baroreceptor drive ratio approximately 4:1. When hemorrhage was performed during autonomic blockade, ECR was 84 units (compared with normal rabbits, P less than 0.01), but blood pressure was poorly maintained and the constrictor effect was not under baroreceptor control. Although the baroreceptors were critical for AVP release during autonomic blockade, they played no role in renin release (ANG II production); the latter was released in large amounts, producing near-maximum constriction, which was unrelated to the afferent input. Thus neurally mediated regulation during hemorrhage has substantial advantages over that mediated primarily through the pressor hormones. PMID- 1877665 TI - Effects of spatial dispersion of acetylcholine release on AV conduction responses to vagal stimulation in dogs. AB - We determined the effects on atrioventricular (AV) conduction of changing the spatial dispersion of acetylcholine (ACh) release from vagal nerve fibers in anesthetized dogs. We paced the atria at a constant rate and stimulated the vagus nerves with one stimulus burst per cardiac cycle. We varied the spatial heterogeneity of ACh release in the cardiac tissues by changing the stimulus voltage, and we varied the quantity of ACh release from each excited nerve fiber by changing the number of pulses per stimulus burst. We slightly changed the stimulus timing with each heartbeat to scan the entire cardiac cycle. We constructed phase-response curves (PRCs) by plotting the changes in AV conduction time as a function of the timing of vagal stimulation. We found that the amplitude of the PRC varied directly with average AV conduction time (AV), whereas the minimum-to-maximum phase difference of the PRC varied inversely with AV. However, for any given change in AV, the specific characteristics of the PRCs did not depend on whether we varied the number of pulses per burst or the stimulus voltage. Therefore, the phase-dependent characteristics of the dromotropic responses appear to be unaffected by the spatial dispersion of ACh release from the vagal nerve endings. The effects of vagal activity on the AV conduction time are determined by those conducting fibers that are the least restrained by neurally released ACh. PMID- 1877666 TI - Influence of hyperglycemia on cerebral adenosine production during ischemia and reperfusion. AB - We hypothesized that systemic hyperglycemia would alter cerebral adenosine concentrations during ischemia and reperfusion. In the present study, we analyzed brain tissue and cerebrospinal fluid (CSF) from hyperglycemic and normoglycemic rats before ischemia, after 15 min of incomplete forebrain ischemia, and during 60 min of reperfusion. Hyperglycemic rats received 3 g/kg of 17% D-glucose intraperitoneally, which increased blood glucose to 357 +/- 23 mg/100 ml compared with 128 +/- 12 mg/100 ml in normoglycemic rats. Brain tissue was sampled by the freeze-blow technique, and CSF was obtained by collecting cortical perfusate from the closed cranial window. Tissue and CSF were analyzed for adenosine and its metabolites inosine and hypoxanthine, and tissue was also analyzed for adenine nucleotides. Hyperglycemia significantly attenuated the increase in brain tissue and CSF adenosine and its metabolites during ischemia while preserving adenine nucleotide concentrates. This attenuation of ischemic adenosine production persisted after 5 min of reperfusion in tissue and throughout 60 min of reperfusion in CSF. Because adenosine, a cerebral vasodilator, can inhibit the release of neuronal excitotoxins as well as affect neutrophil-endothelial interactions, adenosine has been proposed as an endogenous neuroprotector. Thus the attenuation of adenosine and its metabolites may be a factor in the pathogenesis of increased ischemic brain injury associated with systemic hyperglycemia. PMID- 1877667 TI - Evidence of a role for compounds derived from arginine in coronary response to serotonin in vivo. AB - Recent studies have demonstrated that a nitroso compound derived from L-arginine (Arg) may be the endothelium-derived relaxing factor (EDRF) released from vascular endothelium. Synthesis of EDRF from L-Arg is inhibited by analogues of Arg such as NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine (L NNA). We tested the role of compounds derived from Arg in the constriction of the proximal left anterior descending coronary artery (LAD) to serotonin in vivo by measuring responses before and during infusion of L-NMMA or L-NNA. In open-chest anesthetized dogs the LAD was perfused at constant pressure (80 mmHg) from a reservoir. Large-artery diameter was measured with piezoelectric crystals, and coronary flow was measured with an in-line electromagnetic flow probe. Intracoronary serotonin (5 and 50 micrograms/min) caused a dose-dependent constriction of the proximal LAD and increase in coronary flow. Intracoronary L NMMA (2 mg/min) or L-NNA (2 mg/min) augmented the constriction to serotonin, whereas the increase in coronary flow was blunted only by L-NNA. L-Arg (10 mg/min, intracoronary) alone did not alter either the large-artery constriction or the increase in flow to serotonin; however, it prevented the enhanced constriction to serotonin following L-NMMA. Constriction to the endothelium independent agent prostaglandin F2 alpha was not affected by L-NMMA. We conclude that a metabolite of L-Arg modulates the large coronary artery response to serotonin in vivo. PMID- 1877668 TI - Prevention of the oxygen paradox in hypoxic-reoxygenated hearts. AB - Reoxygenation after 60 min substrate-free hypoxic perfusion (modified Tyrode solution, 37 degrees C) caused isolated Langendorff hearts (from rats) to rapidly develop hypercontracture and sarcolemmal disruptions indicated by massive and sudden loss of enzymes ("oxygen paradox"). Reoxygenation (30 min) caused an augmented loss of creatine kinase by 25.8% (lactate dehydrogenase by 40.1%) of the initial total tissue activity. It was investigated whether a temporary contractile blockade by 2,3-butanedione monoxime (BDM; 20 mM) can prevent reoxygenation-induced injury. In the presence of BDM, reoxygenation no longer caused hypercontracture or increased enzyme release. Instead, ultrastructure recovered, and contents of creatine phosphate (CrP) were partially restored (60 min hypoxia: 0.4 mumol CrP/g dry wt; after subsequent 60 min reoxygenation in presence of BDM: 7.8 mumol CrP/g dry wt). When BDM was eluted after first 20 min of reoxygenation, an attenuated but distinct increase in enzyme release was still observed. When BDM was eluted after 60 min of reoxygenation, ultrastructure did not deteriorate and increase of enzyme release remained virtually absent. During first 30 min after removal of BDM, the increased loss of creatine kinase amounted to only 5.7% (lactate dehydrogenase to 6.9%) of the initial total tissue activity. The results demonstrate that the oxygen paradox can be prevented in the hypoxic-reoxygenated heart when the contractile apparatus is temporarily paralyzed during the initial phase of reoxygenation. PMID- 1877669 TI - Periodicities of cardiac mechanics. AB - Using a finite-difference equation to model cardiac mechanics, we simulated the stable action of the left ventricle. This model describes the left ventricular end-diastolic volume as a function of the previous end-diastolic volume and several physiological parameters describing the mechanical properties and hemodynamic loading conditions of the heart. Our theoretical simulations demonstrated that transitions (bifurcations) can occur between different modes of dynamic organization of the isolated working heart as parameters are changed. Different regions in the parameter space are characterized by different stable limit cycle periodicities. Experimental studies carried out in an isolated working rat heart model verified the model predictions. The experimental studies showed that stable periodicities were invoked by changing the parameter values in the direction suggested by the theoretical analysis. We propose in the present work that mechanical periodicities of the heart action are an inherent part of its nonlinear nature. The model predictions and experimental results are compatible with previous experimental data but may contradict several hypotheses suggested to explain the phenomenon of cardiac periodicities. PMID- 1877670 TI - Skeletal muscle metabolism in heart failure in rats. AB - 31P nuclear magnetic resonance (NMR) was used to examine the metabolism of skeletal muscle in rats 6-8 wk after myocardial infarction (MI). These in vivo measurements were supplemented by measurement of creatine, phosphocreatine (PCr), and ATP in freeze-clamped muscle using high-performance liquid chromatography (HPLC) and assays of key muscle enzymes to better define the muscle abnormality observed in heart failure. Resting PCr/(PCr + Pi) and pH were similar in MI rats and controls. Rats with MI had lower pH and PCr/(PCr + Pi) than controls during sciatic nerve stimulation at 1 and 2 Hz. These changes were more severe in rats with large (greater than or equal to 46%) infarcts, and changes in pH and PCr/(PCr + Pi) were correlated with infarct size. Free [ADP] in vivo was estimated from the NMR and HPLC measurements. [ADP] was increased in rats with large infarcts during nerve stimulation, implying a defect in oxidative metabolism. Citrate synthase, a mitochondrial enzyme, was reduced in rats with large MI. Citrate synthase levels were correlated with changes in PCr/(PCr + Pi) at 2 Hz. The NMR changes in skeletal muscle can be explained by reduced oxidative capacity of skeletal muscle, and this proposition is supported by the demonstration of reduced citrate synthase levels in skeletal muscle of rats with large infarcts. PMID- 1877671 TI - Activation of brain adenosine receptors evokes vasodilation in skin arterioles. AB - Metabolically stable adenosine (ADO) agonists were infused into cannulas chronically implanted in the lateral cerebral ventricle intracerebroventricularly (icv) while responses in skin microcirculation of pentobarbital-anesthetized hamsters were observed with intravital microscopy. Cyclohexyladenosine (CHA; A1 receptor selective; 0.0001-1 pmol) and N-ethylcarboxoamidoadenosine (NECA; A2 receptor selective; 0.01-0.05 pmol) were delivered in 10 microliters of bicarbonate-buffered Ringer vehicle. Mean systemic arterial blood pressure, heart rate, skin arteriolar diameter, and red blood cell velocity were continuously monitored. Blood flow was calculated from measurements of arteriolar diameter (20 40 microns) and red blood cell velocity. CHA icv caused dose-related decreases in blood pressure and heart rate, as well as increases in cutaneous perfusion. Comparable amounts of CHA administered intravenously evoked no response. Pretreatment with an A1-selective antagonist xanthine amine congener (XAC, 5 pmol icv or 1 mg/kg iv) had no effect on the depressor response but antagonized the bradycardia. In contrast, a nonselective antagonist 8-phenyltheophylline (8pTHEO, 5 pmol icv or 0.3 mg/kg iv) had no effect on the bradycardia but attenuated the depressor response. By either route, both antagonists prevented the cutaneous microcirculatory responses evoked by icv CHA. NECA icv produced hypotension but no change in the skin, and the depressor response was not altered by icv XAC. These observations provide direct evidence that chemical stimulation of central nervous system (CNS) ADO receptors is linked to a cutaneous vascular response that can be dissociated from other cardiorespiratory depressant actions of CNS ADO. PMID- 1877672 TI - Vasoactive intestinal polypeptide enhances automaticity of supraventricular pacemakers in anesthetized dogs. AB - Effects of the cardiac neuropeptide vasoactive intestinal polypeptide (VIP) and isoproterenol (ISO) were compared on sinus nodal, subsidiary atrial, and atrioventricular junctional pacemaker automaticity in pentobarbital sodium anesthetized dogs (n = 14). Autonomic cardiac nerves were decentralized by bilateral vagotomy and stellectomy. VIP and ISO (30, 100, and 300 pmol/kg iv) were administered during sinus rhythm and either after crushing the sinus node to unmask a latent subsidiary atrial pacemaker (n = 7 dogs) or after injecting pentobarbital sodium into the sinus node artery to elicit an atrioventricular junctional pacemaker (n = 7). Spontaneous sinus nodal, subsidiary atrial, and atrioventricular junctional pacemaker rates (after autonomic nerve decentralization) were 142 +/- 4, 114 +/- 3, and 79 +/- 4 beats/min (means +/- SE), respectively. Both VIP and ISO dose dependently increased the rates of all three pacemaker sites. Combined muscarinic-cholinergic (atropine; 0.11 mg/kg iv) and beta-adrenergic receptor blockade (nadolol; 0.5 mg/kg iv) abolished the stimulatory effects of ISO on subsidiary atrial and atrioventricular junctional pacemakers but did not affect the responses to VIP. We conclude that exogenous VIP enhances the automaticity of sinus nodal, subsidiary atrial, and atrioventricular junctional pacemakers independently of muscarinic-cholinergic and beta-adrenergic receptors. Based on the previous demonstration of VIP immunoreactive nerves throughout the heart, our findings also suggest that endogenous VIP may be involved in cardiac pacemaker regulation. PMID- 1877673 TI - Ischemic contracture begins when anaerobic glycolysis stops: a 31P-NMR study of isolated rat hearts. AB - The relationships among myocardial ATP, intracellular pH, and ischemic contracture in Langendorff-perfused rat hearts were investigated by 31P nuclear magnetic resonance spectroscopy during total global normothermic ischemia while the left ventricular pressure was recorded continuously via an intraventricular balloon. Glucose-perfused hearts (n = 63) were divided into five groups based on the time of onset of contracture (TOC), and three other groups of hearts were treated to vary the ischemic glycogen availability. ATP levels, which showed no evidence of accelerated ATP depletion during contracture, were significant and variable at TOC. Intracellular pH initially declined and then leveled off at TOC, with lower final pH in hearts with later TOC. We conclude that contracture began when anaerobic glycolysis (and thus glycolytic ATP synthesis) stopped. These results, though consistent with the concept that ischemic contracture in normal hearts results from rigor bond formation due to low ATP levels at the myofibrils, suggest that TOC is more closely related to glycolytic ATP production than to total cellular ATP content, thus providing evidence of some degree of subcellular compartmentation or metabolite channeling. In glycolytically inhibited hearts, the quite early contracture may have a Ca2+ component. PMID- 1877674 TI - Sustained effects of endothelin-1 on rabbit, dog, and rat pulmonary circulations. AB - Effects of endothelin-1 (10(-8) M) on the pulmonary vascular resistance compliance profile were examined in isolated blood-perfused rabbit, dog, and rat lungs using occlusion techniques. Capillary permeability was assessed by filtration coefficient (Kfc). Cyclooxygenase products were assessed by radioimmunoassay. In rabbit lungs, endothelin-1 increased all resistances except large vein; ibuprofen reversed the constriction. Endothelin-1 decreased total vascular compliance (CT), which was reversed by ibuprofen. Cyclooxygenase products were unchanged by endothelin-1 or endothelin-1 plus ibuprofen. In dog lungs, large vein resistance increased after endothelin-1; ibuprofen increased large arterial resistance. Endothelin-1 decreased CT and middle compartment compliance, and endothelin-1 plus ibuprofen decreased large vessel compliance (CLV). Ibuprofen reversed the endothelin-1 increase in plasma 6-oxo-prostaglandin F1 alpha. In rat lungs, ibuprofen reversed the endothelin-1 increase in small arterial resistance. Endothelin-1 decreased CLV, and endothelin-1 plus ibuprofen returned the compliance to baseline values. Ibuprofen potentiated the endothelin 1 increase in plasma prostanoids. Endothelin-1 plus indomethacin increased vascular resistance and blocked prostaglandin production. Kfc was increased only in rat lung after endothelin-1 plus ibuprofen. In summary, endothelin-1 increased pulmonary vascular resistance, which was attenuated by prostacyclin in dogs and rats. In rabbits, the resistance increase was reversed by ibuprofen. PMID- 1877675 TI - Whole body vascular capacitance response to vasopressin is mediated by autonomic function. AB - Effects of intravenous infusions of arginine vasopressin (AVP) on whole body vascular capacitance were determined in anesthetized cats when autonomic nervous system function was intact and, in other cats, when reflexes were blocked by the ganglionic blocking agent pentolinium. With the use of the constant cardiac output-reservoir technique, changes in reservoir volume were assumed to reflect reciprocal changes in whole body vascular capacitance. Relationships between the dose of AVP and the plasma concentration of the peptide achieved during infusions were not significantly different in the two groups of animals. Blood pressure responses to AVP were greater, whereas heart rate responses to the peptide were abolished in ganglion-blocked cats. In cats with intact autonomic function, reservoir volume decreased by 1.6, 4.2, and 7.8 ml/kg at AVP doses of 1, 10, and 100 ng.kg-1.min-1, respectively. In contrast, in ganglion-blocked cats, reservoir volume did not change significantly at 1.0 and 10 ng.kg-1.min-1 of AVP, and the highest dose caused a much smaller change in volume (3 ml/kg) than that observed in cats with intact autonomic function (7.8 ml/kg). Systemic compliance was unchanged by AVP in both groups of animals, suggesting that the increases in whole body vascular capacitance were likely due to changes in unstressed volume. The results suggest that reflexively mediated changes in autonomic function increase whole body vascular capacitance during elevations in the circulating levels of AVP to plasma concentrations that are biologically relevant. These findings may explain how AVP decreases cardiac output in animals with an intact autonomic nervous system. PMID- 1877676 TI - Subendocardial coronary compression in beating dog hearts is independent of pressure in the ventricular lumen. AB - Ventricular decompression has been shown to have little effect on either the magnitude or transmural distribution of the extravascular resistance in the small hearts of the cat or rabbit. This study tests whether that independence from ventricular pressure also occurs in the large heart of the dog, which should be more representative of the human. We measured regional myocardial flow in each in situ dog heart during three conditions: normally beating, vented beating, and arrest. Hearts were perfused at constant pressure and maximally dilated with 0.4 1.0 mg/min ic adenosine. Total coronary blood flow was measured with an electromagnetic flowmeter, and regional flow was assessed with radiolabeled microspheres. Although arrest resulted in more than a doubling of flow to the inner layer, greatly reducing ventricular pressure by venting had no significant effect on subendocardial flow. Subepicardial flow was minimally affected by either venting or arrest. We conclude that both the magnitude and the transmural distribution of extravascular resistance in the large heart of the dog is unrelated to the pressure in the ventricular lumen. PMID- 1877677 TI - Segmental vascular resistance during pulsatile and steady perfusion in 3- to 5-wk old rabbit lungs. AB - To determine the mechanisms by which pulsatile perfusion reduces vascular resistance in isolated lungs, we compared the effects of pulsatile versus steady perfusion on total and segmental vascular resistance in isolated lungs of 3- to 5 wk-old rabbits. Lungs were perfused alternately with steady and pulsatile flow for 45-min periods at a constant total arteriovenous pressure drop. Blood flow was adjusted to keep mean pulmonary arterial pressure at 20 cmH2O, when left atrial and airway pressures were 8 and 6 cmH2O, respectively. We partitioned the pulmonary circulation into three longitudinal vascular segments, i.e., arteries, microvessels, and veins, by measuring pressures in 20- to 50-microns-diameter subpleural arterioles and venules by the micropipette servo-nulling method. We found that in the isolated, perfused 3- to 5-wk-old rabbit lung, in which arteries and veins are the main sites of resistance, pulsatile flow results in a 20-36% reduction in total vascular resistance, mainly due to a reduction in arterial and venous resistances. The decrease in total vascular resistance was similar in lungs that were untreated or treated with papaverine, indicating that the effect of pulsatile flow was not due to active vasomotion. The reduction in arterial resistance was greater than that in veins (31-55 vs. 19-22%), especially when pulse amplitude was high (5-10 vs. 20-30 cmH2O). Total vascular resistance was also lower after 45 min of pulsatile perfusion with a pulse rate of 200 pulses/min than 80 pulses/min (0.126 +/- 0.04 vs. 0.154 +/- 0.059 cmH2O.min.ml 1.kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877678 TI - Differential effects of intra- and extraluminal endothelin on cerebral arterioles. AB - The differential effects of intraluminal and extraluminal application of endothelin, the endothelium-derived constricting factor, were studied in isolated intracerebral arterioles that were cannulated and perfused in vitro. Extraluminal and intraluminal application of 10(-8) M endothelin constricted the arterioles to 38.2 +/- 6.7 and 75.1 +/- 5.7% of the control diameter, respectively. Constrictions induced by either the intraluminal or the extraluminal application of endothelin were inhibited in a Ca(2+)-free solution. Nimodipine attenuated, but did not completely abolish, the constriction induced by the extraluminal application of endothelin, but it did abolish the constriction induced by the intraluminal application. The duration of vasoconstriction also differed between intra- and extraluminal application. Vessel diameter quickly returned to the control value as soon as intraluminal perfusion of endothelin was terminated. In contrast, the constriction induced by extraluminal application of endothelin lasted much longer and was difficult to reverse. The differential effect of intraluminal and extraluminal endothelin application appears to reflect the important barrier-function of the cerebrovascular endothelium of intracerebral arterioles. PMID- 1877679 TI - Regional function, blood flow, and oxygen utilization relations in repetitively occluded-reperfused canine myocardium. AB - Temporary coronary occlusion followed by reperfusion severely reduces contractile function in the involved segment. We tested whether an uncoupling exists between O2 utilization (MVO2) and systolic shortening in the ischemic-reperfused segment subjected to repetitive coronary occlusion and reperfusion. In 10 anesthetized open-chest dogs, left ventricular pressure and segment length (sonomicrometry) relations were measured in the left anterior descending (LAD, ischemic reperfused) segment and circumflex coronary artery (nonischemic segment). Four 12 min LAD occlusions were each followed by 30 min reperfusion. MVO2 was determined in both segments by transmural blood flow (15 microns microspheres) and regional coronary arterial-venous O2 extraction after each occlusion-reperfusion period. The four occlusion-reperfusion periods did not produce necrosis by staining with triphenyltetrazolium chloride. LAD occlusion produced dyskinesis [control = 16 +/ 3.0% systolic shortening (SS) vs. -8.8 +/- 1.5%, P less than 0.0001]. The first reperfusion restored SS only to 2.3 +/- 2.0%, which progressively deteriorated to -3.9 +/- 1.1% (P less than 0.05) with subsequent occlusion-reperfusion episodes. Relative to the nonischemic segment, MVO2 in the ischemic-reperfused segment decreased by only 18% despite dyskinesis. Pressure-length analysis showed systolic stiffening during reperfusion with displacement of the passive ischemic pressure-length loop to the left. Segment work (integral of each loop) continued to be generated at 34.5% of control levels after the last occlusion-reperfusion event in contrast to the negative SS. We conclude that 1) MVO2 in the ischemic reperfused segment without necrosis remains elevated despite severe reductions in systolic shortening, and 2) the discrepancy between systolic shortening and MVO2 is partially due to persistent development of segment work. PMID- 1877680 TI - Polyethylene glycol-conjugated superoxide dismutase fails to blunt postischemic reactive hyperemia. AB - We tested the hypothesis that superoxide dismutase (SOD) conjugated with polyethylene glycol (PEG-SOD) would alter hyperemia following complete global cerebral ischemia. Thirty minutes before ischemia pentobarbital-anesthetized piglets were assigned to receive 3 ml of either PEG-SOD (10,000 U/ml; n = 10), an equivalent concentration of PEG (n = 10), or saline (n = 10) in a randomized and blinded manner. Cerebral ischemia was sustained for 10 min by cross-clamping the ascending aorta. Measurements of cerebral blood flow (radiolabeled microspheres) and oxygen consumption were made before ischemia and at 2, 4, 8, 12, and 15 min of reperfusion. Plasma SOD activity was higher in PEG-SOD-treated piglets (134 +/ 8 U/ml) than in PEG or saline-treated piglets (less than 5 U/ml). All groups and all brain regions demonstrated postischemic hyperemia. There were no differences in blood flow between groups at any time point in any region. At 2 min of reperfusion, blood flow to cerebrum rose from 31 +/- 4 to 88 +/- 9 ml.min-1.100 g 1 (saline), 44 +/- 6 to 102 +/- 17 ml.min-1.100 g-1 (PEG), and 31 +/- 3 to 83 +/- 16 ml.min-1.100 g-1 (PEG-SOD). During reperfusion cerebral oxygen consumption was not different from preischemic values in any group. In conclusion, we demonstrated that exogenously administered PEG-SOD raises serum SOD activity but does not alter the patterns of early cerebral blood flow or metabolic recovery after 10 min of complete global cerebral ischemia in piglets. PMID- 1877681 TI - Vasorelaxant effects of short chain fatty acid salts in rat caudal artery. AB - Acetate relaxes rat caudal artery and increases tissue adenosine 3',5'-cyclic monophosphate (cAMP) levels. The present study's purpose was to determine whether related ultrashort chain (volatile) fatty acids, propionate (C3), butyrate (C4), and octanoate (C8) would do so as well. It was found that butyrate and propionate had very similar vasorelaxant profiles to acetate; they relaxed caudal artery strips precontracted with KCl, phenylephrine, arginine vasopressin, and prostaglandin F2 alpha. The vasorelaxation was endothelium independent, was not blocked by indomethacin, and was associated with a rise in tissue cAMP levels but not in guanosine 3',5'-cyclic monophosphate (cGMP) levels. The mean effective concentration for butyrate (0.8 mM) was lower than that for acetate (2.0 mM) or propionate (1.9 mM). Propionate-mediated relaxation was blocked by the stilbene inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Vasorelaxant effects of octanoate were also not dependent on endothelium and were not affected by indomethacin. Maximal vasorelaxant effect of octanoate was greater than that of acetate, propionate, or butyrate; vasorelaxant effect of octanoate was only slightly attenuated by DIDS and was associated with only a minimal effect on tissue cAMP levels. Results suggest that vasodilatory effects of acetate generalize to propionate and butyrate, but that vasorelaxant effects of octanoate may be occurring via a separate mechanism. PMID- 1877682 TI - Efficacy of Cushing response during development in sheep. AB - Mean aortic pressure (MAP) increases (Cushing response) when intracranial pressure (ICP) approaches MAP. We elevated ICP to levels equivalent to normal baseline MAP with infusion of mock cerebrospinal fluid (CSF) into the lateral cerebral ventricles and contrasted responses in near-term fetal sheep, 1-wk-old lambs, and adult sheep anesthetized with pentobarbital sodium. With CSF infusion 1-wk-old lambs and adults produced sustained increases in MAP of 16 +/- 1 and 22 +/- 2 mmHg, respectively, over a 40-min period. However, cerebral blood flow fell 66 and 57%, and cerebral O2 uptake fell 34 and 37%, respectively. In the near term fetus, MAP increased by 11 +/- 1 mmHg and cerebral blood fell 49% at 3 min of elevated ICP. However, by 15 min MAP had increased further (+17 +/- 2 mmHg) and cerebral blood flow was nearly restored. In contrast to postnatal sheep, cerebral O2 uptake was maintained throughout in the fetus. The mechanism of increased MAP differed among groups. In adults total peripheral resistance fell significantly, whereas in the fetus and lamb it remained constant. Cardiac output increased in each group, but, because of the fall in peripheral resistance, increased cardiac output was relatively more important to the rise in MAP in adults. In addition, marked vasoconstriction occurred in intestines and skin in the fetus. The Cushing response is well-developed in near-term fetal sheep. After birth it may lose its effectiveness in providing for the basal metabolic demand of the brain. PMID- 1877683 TI - Two new inbred rat strains derived from SHR: WKHA, hyperactive, and WKHT, hypertensive, rats. AB - Two new strains of inbred rats have been developed. One, WKHA, exhibits hyperactivity, and the other, WKHT, exhibits hypertension. Both of these traits are expressed in the SHR. By crossing spontaneously hypertensive rats (SHRs) with Wistar-Kyoto (WKY) controls, followed by recombinant selected inbreeding, we succeeded in genetically separating the hyperactivity from the hypertension in two new strains. Longitudinal studies indicate a persistence of hypertension without hyperactivity in WKHTs, and hyperactivity without hypertension in WKHAs, over at least 1 year. Ventricular enlargement, another characteristic of SHRs, was observed in adult WKHTs after the onset of hypertension; however, ventricles were already enlarged in normotensive WKHAs at 6 wk. The emergent behavioral profile of WKHAs indicates that they retain the hyperactivity trait and hyperreactivity to stress, and not some of the other behaviors of SHRs, such as poor habituation. Studies in WKHTs suggest that they are an improvement over SHRs as a model of genetic hypertension as they lack some prominent behavioral abnormalities. Nevertheless, the four genetically related strains (WKHA, WKHT, SHR, and WKY), used together, are considered most appropriate for seeking correlations of biological differences with either hypertension or hyperactivity. PMID- 1877684 TI - Oxygen metabolite effects on creatine kinase and cardiac energetics after reperfusion. AB - Noninvasive 31P nuclear magnetic resonance measurements indicate that during the initial reperfusion phase myocardial tissue contents of phosphocreatine (PCr) recover rapidly, while ATP levels remain low and recover slowly. There is also a burst of H2O2 during the first 10 min of reperfusion, as indicated by the in vivo inactivation of catalase that occurs only when H2O2, and the inactivator 3 aminotriazole (AMT), are simultaneously present. Neither H2O2 production nor CK inactivation was discernable after ischemia alone. In excitable tissue the PCr and ATP pools are equilibrated by the enzyme creatine kinase (CK), but myocardial CK activity is decreased by 20% after reperfusion, though not by simple washout. Extrapolating from the well-known air sensitivity of CK, we find that limited exposure in vitro to small concentrations of H2O2 can markedly diminish CK activity. We postulate that failure of certain CK isoenzymes at energy-using termini may decouple the relative rates of PCr production and ATP regeneration and hence cause elevated PCr-to-ATP ratios. The assumptions of 1) CK equilibrium during the reperfusion period to calculate free ADP levels and 2) cardiac recovery deduced from the elevation of PCr levels may require reexamination. PMID- 1877685 TI - Pentobarbital produces dissimilar changes in glucose influx and utilization in brain. AB - The effects of pentobarbital sodium on local cerebral glucose utilization (LCGU) and 3-O-methylglucose (3-MG) influx were measured by quantitative autoradiography in 52 brain areas of control and treated rats. Pentobarbital (50 mg/kg ip) lowered LCGU to a relatively uniform rate (approximately 35 mumol.100 g-1.min-1) in 24 of 25 forebrain areas. Among the 18 hindbrain areas, LCGU was decreased by pentobarbital by 15-55% (range 50-157 and 28-110 mumol.100 g-1.min-1 in control and treated rats, respectively). In contrast, pentobarbital lowered the 3-MG influx rate constant and permeability-surface area product by 20-30% in nearly all brain structures. The 3-MG results fit a model in which both the half saturation constant and the maximal velocity of the glucose carrier are decreased by pentobarbital. After pentobarbital treatment, the ratio of local cerebral plasma flow (LCPF) to LCGU was the same as in controls for brain areas in which LCGU was less than 35 mumol.100 g-1.min-1 but was higher in brain areas where LCGU exceeded 35 mumol.100 g-1.min-1. Pentobarbital produced dissimilar changes in LCGU, 3-MG influx, and LCPF; these processes may thus not be closely linked during pentobarbital anesthesia. PMID- 1877686 TI - Sympathetic nerve activity and renal responses during continuous negative pressure breathing in humans. AB - A stretch stimulus of the cardiopulmonary receptors results in a diuresis and natriuresis in dogs due to a suppression of renal sympathetic nerve activity. In the present experiment, the stretch stimulus in humans was given by means of continuous negative-pressure breathing (CNPB), and muscle sympathetic nerve activity (MSNA), renal responses, and hormones were measured to examine whether MSNA response during CNPB correlated with the usual renal and hormonal responses for stretch stimulus of the cardiopulmonary receptors. Nine healthy males were subjected to CNPB at -11 mmHg for 60 min. MSNA in the peroneal muscle nerve fascicles was measured continuously before (pre-CNPB), during, and after CNPB (post-CNPB). A step and sustained decrease (P less than 0.05) in MSNA (30 +/- 6% for burst frequency and 37 +/- 4% for total activity from pre-CNPB level) was observed during CNPB and it returned to pre-CNPB level at post-CNPB. Urinary excretion increased by 58 +/- 18% (P less than 0.05) during CNPB, and the diuresis was entirely osmolal in nature because of a significant increase (P less than 0.05) in Na excretion and a constant free-water clearance. The plasma level of norepinephrine decreased significantly (P less than 0.05) during CNPB and remained decreased (P less than 0.05) at post-CNPB. A twofold increase (P less than 0.05) in plasma atrial natriuretic peptide and a 35 +/- 9% reduction (P less than 0.05) in plasma renin activity were observed during CNPB, whereas no change was observed in plasma aldosterone and arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877687 TI - Physiological consequences of NaCl ingestion by Na(+)-depleted rats. AB - We investigated the temporal relationships between NaCl intake, gastrointestinal Na+ content, and plasma concentrations of Na+, aldosterone, and plasma renin activity (angiotensin). Rats depleted of approximately 2.2 mmol Na+ by combined dietary Na+ restriction and furosemide injection (10 mg sc) drank a preload of 1, 2, or 3 mmol 0.5 M NaCl. Intake of a test 0.5 M NaCl solution given 15, 30, 60, or 120 min later was reduced by approximately 50% of the preload content, irrespective of the interval between preload and test. At 15 min after starting to drink, 61-71% of ingested Na+ remained in the stomach, 15-18% in the small intestine, approximately 5% was calculated to be in extracellular fluid, and less than 1% was excreted. Rates of gastric and gastrointestinal clearance of Na+ were related to the quantity of NaCl ingested. Whereas gastric emptying was initially very rapid (30-61 mumol/min) and decreased with time, gastrointestinal clearance was constant (16-39 mumol/min). Drinking 3 mmol NaCl reliably reduced plasma aldosterone concentrations within 15 min and renin activity within 30 min. Drinking 1 or 2 mmol NaCl reliably reduced levels of these hormones within 30-60 min. The results describe for the first time the distribution of Na+ after Na(+) depleted rats drink NaCl. They suggest that the rat determines the quantity of Na+ it requires within the first 15 min of ingestion and thus does not depend on signals generated by the prolonged influence of Na+ in the gastrointestinal tract or the fall in plasma concentrations of aldosterone and angiotensin. PMID- 1877688 TI - Arterial baroreflex control of cardiac and renal sympathetic nerve activities is uniform in frequency domain. AB - To investigate wideband dynamic properties of arterial baroreflex control of cardiac and renal sympathetic nerve activities, we assessed the transfer function using a "white-noise technique." In pentobarbital sodium-anesthetized cats, we simultaneously recorded, as the output, cardiac sympathetic nerve activity (CSNA) and renal sympathetic nerve activity (RSNA), while aortic pressure (AP) was randomly perturbed to impose input pressure changes with broad frequencies. We calculated the transfer function from AP to CSNA or to RSNA over the frequency range of 0.01-5 Hz through the spectral analysis of the input and output. We found that the gain, phase shift, and coherence of those transfer functions were statistically indistinguishable. The gain was rather flat below 0.05 Hz, steadily increased above 0.05 Hz, and plateaued above 0.3 Hz. The phase shift was out of phase up to 0.05 Hz and led by approximately 4 degrees above 0.05 Hz. The coherence was high (above 0.7) below 0.3 Hz and became lower above 0.3 Hz. These results suggest that arterial baroreflex control is uniform and similar between the two activities in the frequency range of 0.01-0.7 Hz. PMID- 1877689 TI - Intravenous nutrient-induced satiety depends on feeding-related gut signals. AB - To determine whether feeding-generated gut signals act in conjunction with intravenous nutrients to suppress food intake, nutrients were infused intravenously to dark-fed rats during different portions of the 12:12 h light dark cycle. During 4-day test periods rats received 35.5-37 kcal/day of a solution containing 25% glucose-4.25% amino acids. Food intakes were reduced by 40.5 +/- 1.1 and 30.7 +/- 1.8 kcal or 110 and 87% of the calories infused in the dark (fed) phase over 8 and 12 h, respectively. When administered in the light phase while rats were fasted, 8- and 12-h infusions reduced food intake significantly less than in the dark: 21.3 +/- 1.1 and 19.6 +/- 0.7 kcal/day or only 57 and 55% of the infused calories, respectively. With 24-h infusions, as in previous studies, food intake was reduced by 24.5 +/- 2.1 kcal/day or 68% of the infused calories. These results suggest that gut signals generated by concurrent feeding act with intravenous glucose and amino acids to produce a more compensatory reduction in daily food intake. PMID- 1877691 TI - Amiloride sensitivity of chorda tympani response to NaCl in Fischer 344 and Wistar rats. AB - Fischer 344 (F-344) rats fail to prefer NaCl solutions to water at any concentration and avoid NaCl solutions preferred by other strains, including Wistar rats. Behavioral and electrophysiological responses of the mammalian gustatory system to NaCl have been shown to depend on a sodium transport system that is specifically blocked by lingual application of the sodium-transport blocker amiloride. The present study examined whether strain differences exist between F-344 and Wistar rats in the amiloride sensitivity of the chorda tympani (CT) electrophysiological response to NaCl. Whole nerve CT recordings were obtained from adult F-344 and Wistar rats during chemical stimulation of the anterior tongue. Responses to NaCl solutions ranging from 0.01 to 1.0 M were examined both before and after pretreatment with amiloride hydrochloride. Integrated whole nerve responses to NaCl solutions were expressed relative to the response to 0.5 M NH4Cl. Strain differences in the response to NaCl solutions emerged, with F-344 animals showing a significantly larger amplitude of the tonic response to NaCl, relative to NH4Cl, than Wistars. F-344 rats were also more sensitive to the sodium-channel blocker amiloride. These results suggest that strain differences in amiloride sensitive signals mediated by the CT nerve may contribute to the NaCl aversion displayed by F-344 rats. PMID- 1877690 TI - Endothelium-derived relaxing factor in regulation of basal cardiopulmonary and renal function. AB - The endothelium has emerged as an important modulator of vascular tone by producing both vasodilating and vasoconstricting substances. In vitro studies have demonstrated that endothelial cells produce endothelium-derived relaxing factor (EDRF), which promotes vasodilation via the stimulation of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). However, the role of EDRF in the basal regulation of cardiopulmonary and renal function is not well defined. The present study was therefore designed to assess the function of EDRF by studying two groups of normal anesthetized dogs, of which one received a competitive inhibitor to EDRF generation, NG-monomethyl-L-arginine (L-NMMA; 50 micrograms.kg 1.min-1 iv), and the other received a vehicle. The L-NMMA infusion produced no significant increase in mean arterial pressure but marked increases in systemic, pulmonary, and renal vascular resistances compared with the vehicle group. Although renal blood flow decreased with L-NMMA, no changes were observed in glomerular filtration rate or sodium excretion. Associated with the cardiopulmonary and renal responses with L-NMMA was a modest increase in plasma endothelin (7.9 +/- 1.3 to 10.2 +/- 1.8 pg/ml, P less than 0.05), an endothelium derived vasoconstrictor. No alteration was observed in plasma or urinary cGMP with EDRF inhibition. These cardiopulmonary and renal responses with L-NMMA may be attributed not only to EDRF inhibition but to an imbalance between endothelium derived relaxing and contracting factors. PMID- 1877692 TI - Drinking after osmotic challenge depends on circadian phase in rats with free running rhythms. AB - Rhythmic phase-dependent modulation of the amount of water intake of rats occurs after several types of dipsogenic treatments. Previous studies conducted on rats in light-dark cycles confound direct effects of the light-dark cycle with the effects of circadian rhythmicity entrained to the light-dark cycle. The present study isolates the effect of circadian phase on the amount of drinking induced by injection of hypertonic saline. Free-running rhythms were induced in rats, and then water intake was measured after injections of both hypertonic and isotonic saline at different phases of the rats' circadian cycle. After injections of hypertonic saline, rats drank more water in their active phase than in their inactive phase. No difference in the amount of intake was found in rats that received isotonic saline at different phases of their circadian rhythms. The results indicate a circadian modulation of the drinking induced by cellular dehydration. PMID- 1877693 TI - Influence of fatty acid oxidation in lateral hypothalamus on food intake and body composition. AB - This study tested the concept that the level of fatty acid oxidation in the ventrolateral hypothalamus (VLH) reflects peripheral energy stores and elicits compensatory responses to changes in energy balance status. Fatty acid oxidation rates in the VLH were chronically altered over a 14-day period by infusing into the VLH either 0.1 mM 4-pentenoic acid (4-PA; 5 ng/h) or 1.0 mM L-carnitine (L Carn; 98 ng/h). Fatty acid oxidation rates in the VLH were altered to a similar extent as by overfeeding (reduced 37% by 4-PA) and dietary restriction (increased 28% by L-Carn). Diffusion of infusates was limited, since there were normal rates of fatty acid oxidation in the ventromedial hypothalamus and cortex. There were no significant effects of altering fatty acid oxidation in the VLH on food intake, body weight, body composition, or serum levels of glucose, insulin, and free fatty acids. The results of this experiment indicate that the level of fatty acid oxidation in the VLH is unlikely to independently elicit changes in food intake or peripheral metabolism. PMID- 1877694 TI - Association between decreased splenic ATP levels and immunodepression: amelioration with ATP-MgCl2. AB - Although it is known that decreased ATP levels in liver and kidney contribute to organ dysfunction after shock, it remains unknown whether there is any association between decreased splenocyte ATP levels and splenic immune functions. Moreover, although studies have shown that ATP-MgCl2 treatment after shock improves hepatic and renal ATP levels and organ function, it remains unknown whether splenocyte ATP levels and immune functions are similarly affected by this agent. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mmHg, maintained at that pressure for 60 min, resuscitated with shed blood and Ringer lactate, and treated with ATP-MgCl2 (80 mumol/kg) or vehicle (saline). Splenocytes (SPL) were harvested at various intervals after hemorrhage, ATP levels were assessed by 31P nuclear magnetic resonance spectrometry, and functions were determined by measuring proliferative capacity and interleukin (IL)-2, and IL-3 synthesis. Hemorrhage depleted SPL ATP levels to 1.7 +/- 0.8% of control levels. However, there was a significant increase in ATP levels of ATP MgCl2-treated mice (77 +/- 11%, P less than 0.05) compared with vehicle-treated animals (13 +/- 4.1%) at 1 h after resuscitation. SPL ATP levels returned to control by 2 h after resuscitation in the ATP-MgCl2 group, whereas ATP levels of the vehicle-treated mice remained significantly depressed (P less than 0.05) for up to 12 h after resuscitation. At 1 h after resuscitation, SPL proliferative capacity and IL-2 and IL-3 synthesis were all profoundly depressed in the vehicle treated group (P less than 0.05 vs. control).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877695 TI - Pethidine (meperidine) inhibition of oxytocin secretion and action in parturient rats. AB - Pethidine (also known as meperidine and as Demerol) injected subcutaneously at 10 mg/kg into parturient rats on the birth of the second pup resulted in a marked slowing of the progress of parturition, associated with reduced plasma oxytocin concentrations. Injection of the opiate antagonist naloxone counteracted the inhibition of oxytocin secretion and largely prevented the slowing of parturition. In vitro, pethidine inhibited spontaneous, oxytocin-induced and acetylcholine-induced contractions of uteri from rats immediately post partum, and these effects were not reversed by naloxone. In anesthetized lactating rats, pethidine inhibited the suckling-induced milk-ejection reflex and attenuated oxytocin-induced contractions of mammary myoepithelium. Finally, pethidine depressed plasma oxytocin concentrations in rats given 2% saline to drink for 24 h to stimulate oxytocin secretion. Thus pethidine inhibits oxytocin secretion in all three conditions; this inhibition is probably mediated by central opioid receptors. In addition, however, pethidine depresses the oxytocin responsiveness both of mammary myoepithelium and of myometrium. The latter effect at least is not opioid mediated. PMID- 1877696 TI - Loss of integrative control of peripheral circulation during desynchronized sleep. AB - Regional blood flow (BF) changes during sleep were measured in rabbits at low, neutral, and high ambient temperatures (Ta) with radioactive microspheres. At both low and high Ta, peripheral vasomotor changes at the onset of desynchronized sleep (DS) were incompatible with thermoregulatory homeostasis. At low Ta, BF decreased in muscle (with the disappearance of shivering), whereas it increased in the arteriovenous anastomoses (AVA) and in the splanchnic bed. At high Ta, BF decreased in muscle (with the disappearance of panting) and in the AVA, whereas it increased in the splanchnic bed. An impaired central nervous regulation underlies the disruption of peripheral circulation patterns in this sleep stage. The lack of adaptive vasomotor adjustments in DS, which has little consequence in normal conditions, may become relevant in cardiovascular pathophysiology when BF redistribution through increased neurogenic vasomotor activity becomes a major compensating mechanism. PMID- 1877697 TI - Myocardial aging: antioxidant enzyme systems and related biochemical properties. AB - The effects of aging on myocardial antioxidant enzyme activity, lipid peroxidation, and other related biochemical properties were investigated in male Wistar-Furth rats at 4, 26, and 31 mo of age at rest and after an acute exercise bout. The results showed that resting heart cytosolic superoxide dismutase (CuZn SOD) activity was significantly decreased in the heart with aging (66 +/- 6.5 U/mg protein at 4 mo vs. 49 +/- 3.8 U/mg protein at 31 mo) and was elevated in all age groups after exercise. Mitochondrial Mn SOD activity was almost doubled in both 26- and 31-mo-old rats compared with that at 4 mo. Myocardial catalase and cytosolic glutathione peroxidase (GPX) activities were significantly decreased with age, whereas mitochondrial GPX was 29% higher (P less than 0.05) in 31- than 4-mo-old rats. Glutathione S-transferase activity in the heart also declined with age (P less than 0.05 at 31 mo). Malondialdehyde contents in both heart homogenate and mitochondria were significantly increased at old age. Activity of several enzymes related to myocardial energy production, e.g., citrate synthase, malate dehydrogenase, and lactate dehydrogenase, as well as myocardial protein content showed an age-related decline. These data indicate that myocardial antioxidant capacity is weakened during aging and that the compensatory increases of mitochondrial SOD and GPX may be an important mechanism in coping with free radical damage in senescent heart. Findings in the present investigation seem to support the free radical theory of aging. PMID- 1877698 TI - Fetal fluid responses to long-term 5 M NaCl infusion: where does all the salt go? AB - The fetus must obtain Na and Cl ions in order to grow. However, the regulation of electrolyte acquisition by the fetus is not well understood. To explore fetal electrolyte balance, we intravenously infused 5 M NaCl at a rate equal to 80% of the total fetal body Na+ and Cl- content per day (240 mM/day) for 3 days into late-gestation fetal sheep. We hypothesized that the increase in fetal osmolality resulting from the infusion would cause a transplacental water movement into the fetal compartment, leading to hydrops fetalis and/or polyhydramnios. The fetal-to maternal osmotic gradient was initially -2.8 +/- 0.9 (SE) mosmol/kgH2O and rose by 4.8 +/- 1.8 mosmol/kgH2O during the infusion. Fetal plasma [Na+] and [Cl-] increased (3.0 +/- 0.4 and 5.5 +/- 0.5 meq/l, respectively), but the normal maternal-to-fetal transplacental concentration gradients for these ions were not reversed. Most of the infused Na+ (92 +/- 14%) and Cl- (82 +/- 12%) was excreted by the fetus in large volumes of hypotonic urine. Amniotic fluid osmolality and [Na+] were unchanged, but amniotic [Cl-] increased 5.7 +/- 2.4 meq/l. The amniotic plus allantoic fluid volume, as estimated by ultrasonography, was increased (43.5 +/- 14.5%) at day 2 and returned to control by day 3 of infusion. There was no fetal edema during the study or at autopsy. In light of these results, we propose a novel and somewhat complex mechanism for transplacental fluid and electrolyte movement in which placental capillary permeability increases along the length of the capillary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877699 TI - Interactions between brain acetylcholine and prostaglandins in control of vasopressin release. AB - We have examined in conscious rats the interaction between centrally acting prostanoids and acetylcholine in the stimulation of vasopressin secretion. The intracerebroventricular (icv) administration of carbachol (25 ng) resulted in marked transient increases in the plasma vasopressin concentration and mean arterial blood pressure and a transient reduction in heart rate. Central cyclooxygenase blockade by pretreatment icv with either meclofenamate (100 micrograms) or indomethacin (100 micrograms) virtually completely blocked these responses. Prostaglandin (PG) D2 (20 micrograms icv) caused transient increases in the plasma vasopressin concentration (much smaller than after carbachol) and heart rate, whereas mean arterial blood pressure rose gradually during the 15-min course of the experiment. Pretreatment with the muscarinic antagonist atropine (10 micrograms icv) decreased the peak vasopressin response to icv PGD2 by approximately one-third but had no effect on the cardiovascular responses. We conclude that the stimulation of vasopressin release by centrally acting acetylcholine is dependent on increased prostanoid biosynthesis. On the other hand, stimulation of vasopressin release by icv PGD2 is partially dependent on activation of a cholinergic pathway. PMID- 1877700 TI - Functional evidence for sympathetic nerve activity in conscious cervical spinal rats. AB - Experiments in anesthetized animals have demonstrated sympathetic nerve activity after cervical spinal cord transection (CST), yet little evidence exists for sympathetic nerve activity in conscious spinal animals. We determined the effect of CST on mean arterial pressure (MAP), heart rate (HR), and plasma renin activity (PRA) in conscious rats. Next, we tested for the presence of functionally significant sympathetic nerve activity 24 h after CST by measuring MAP, HR, urine flow, urinary sodium excretion (UNaV), urinary potassium excretion (UKV), and PRA before and for 2 h during administration of adrenergic antagonists (propranolol + phentolamine) or vehicle. CST resulted in significant decreases in MAP (100.0 +/- 1.6 to 75.0 +/- 1.4 mmHg), HR (353 +/- 7.5 to 315 +/- 6.6 beats/min), and PRA (2.2 +/- 0.3 to 1.2 +/- 0.2 ng angiotensin I.ml-1.h-1). Subsequent adrenergic blockade resulted in a further drop in HR (-52 +/- 21 beats/min), as well as two- to threefold increases in UNaV and UKV. We conclude that CST causes an overall decrease in sympathetic drive. However, sympathetic nerve activity to the heart and kidney remains after CST and is responsible for support of HR and retention of sodium and potassium. PMID- 1877701 TI - Developmental changes in ovine cerebral artery composition and reactivity. AB - We have examined age-related changes in segments of common carotid (Com), basilar (Bas), posterior communicating (PC), and middle cerebral (MC) arteries taken from 14 near-term fetal lambs, 62 newborn lambs 3-7 days old, and 42 adult nonpregnant sheep. Transition from fetal to newborn life was associated with a decreased water content in all arteries ranging from 0.6% (Com) to 2.3% (Bas), no change in the relative content of cellular protein, an increase in wall thickness ranging from 4% (MC) to 26% (Com), an increase in maximum contractile tension ranging from 18% (MC) to 82% (Com), an increase in stiffness, an increase in the maximum active stress ranging from 6% (Bas) to 43% (Com), a decrease in the amine-to potassium ratio (calculated as the maximum response to 10 microM serotonin with 20 microM histamine divided by the maximum response to 122 mM K+) ranging from 8% (Bas) to 51% (Com), and a decrease in the norepinephrine-to-potassium ratio ranging from 2.1% (Bas) to 56% (Com). Thus developmental changes associated with the transition from fetal to newborn life were much more pronounced in the larger, more proximal Com than in the smaller, more distal cerebral arteries, suggesting that, at term, the cerebral arteries are more mature both functionally and structurally than the Com arteries. Similarly, the transition from newborn to adult life was associated with much greater changes in Com characteristics than with those of the cerebral arteries. These studies demonstrate that the effects of aging vary considerably along the cerebrovascular tree and that conclusions based on developmental studies of large systemic arteries cannot be freely extrapolated to the smaller arteries of the circle of Willis. PMID- 1877702 TI - Endometrial transport generates the maternal-fetal electrical potential difference in guinea pigs. AB - These studies examined the transport characteristics of the uterine endometrium with respect to the origin and mechanism of generation of the maternal-fetal electrical potential difference (PD) in pregnant guinea pigs. Late-gestation animals were used in two experimental preparations. In vivo, a sealed uterine pouch that preserved blood flow to the endometrium was prepared by removal of the fetus, placenta, and fetal membranes from the uterus and replacement with Earle's solution, a balanced electrolyte solution. In vitro, sections of uterine wall comprised of myometrium and endometrium without fetal membranes were mounted in Ussing chambers. Transuterine PDs (fetal side negative) were indistinguishable in vivo and in vitro, averaging 29.6 +/- 4.5 and 32.6 +/- 6.1 (95% confidence interval) mV in the respective preparations. Both values are within the range of maternal-fetal PD measured in intact guinea pigs, indicating that the fetoplacental unit is not essential in generating an intrauterine PD. The maternal-fetal PD, therefore, is likely a passive result of the fetus and placenta being immersed in fluids at the intrauterine potential. In vitro, both PD and short-circuit current (Isc) were completely inhibited by ouabain (10(-3) M) at the serosal (maternal) side of the uterine wall but unaffected by the inhibitor from the luminal (fetal) side. Amiloride (10(-5) M) and valinomycin (10(-5) M) caused decreases in the PD when added to the luminal side, both in vivo and in vitro, and were both ineffective from the serosal side in vitro. Isc was reduced 83% from 315 +/- 24 to 53 +/- 6 (SE) microA/cm2 after luminal amiloride (5 x 10(-4) M), indicating that Na+ is the predominant ion actively transported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877703 TI - Angiotensin II does not contribute to rapid reflex control of arterial pressure. AB - Pharmacological blockade of the renin-angiotensin converting enzyme reportedly alters the heart rate (HR) power spectrum in conscious dogs, suggesting that these hormones contribute to the short-term regulation of arterial blood pressure. We tested this possibility using four independent procedures. First, HR power spectrum was determined in seven awake dogs before and after administration of enalaprilat (300 ng/kg), a converting-enzyme inhibitor. There were no significant changes in the average amplitude for the spectral peak between 0.003 and 0.1 Hz (i.e., the "low-frequency peak"). Second, the HR power spectrum was measured in 11 awake rabbits before and after treatment with deoxycorticosterone acetate (1 mg.kg-1.day-1) and salt (0.9% saline ad libitum) for 7 days to depress plasma renin levels. There were no significant changes in the amplitude of the HR power spectrum, although mean HR decreased from 206 +/- 3 to 184 +/- 4 beats/min after treatment. In the third experiment, another group of rabbits (n = 8) was tested after 2 wk on a low-salt diet to elevate plasma angiotensin levels and then after 2 wk on a normal salt diet. Once again there were no significant effects on the HR power spectrum. Finally, tranquilized dogs (n = 9) were subjected to sinusoidally varying lower body negative pressure at selected frequencies of 0.008-0.12 Hz. Tests were conducted in the control state and after administration of an angiotensin receptor antagonist (saralasin, 1 microgram.kg 1.min-1). Lower body negative pressure-induced fluctuations in arterial blood pressure were similar in both states. We find no evidence for the role of the renin-angiotensin system in the moment-to-moment regulation of arterial pressure and HR. PMID- 1877704 TI - Regional blood-brain barrier transport of cationized bovine serum albumin in awake rats. AB - Regional blood-brain barrier permeability-surface area products (PAs) of cationized bovine serum albumin (cBSA) with isoelectric point (pI) approximately 8 or greater than or equal to 11 and of native bovine serum albumin (nBSA;pI approximately 4) were determined in awake male Sprague-Dawley rats after bolus intravenous injection. The albumins were labeled with 125I. Brain uptakes were assessed by autoradiography and by direct assay of radioactivity in brain regions. nBSA uptake into brain was statistically insignificant over 3 h, whereas cBSA uptake was significantly even at 6 min. Mean PA values of cBSA with pI approximately 11 (1.69-2.65 x 10(-5) ml.s-1.g-1) in most brain regions were twofold higher than PAs of cBSA with pI approximately 8 (0.98-1.37 x 10(-5) ml.s 1.g-1), whereas mean PA for nBSA did not differ significantly from zero. Autoradiographs of brain slices and net distributions in brain compartments at 6 and 30 min after injection suggested that cBSA entered the brain parenchyma via blood vessels and cerebrospinal fluid but that the former was the main route. The results quantitate for the first time regional brain PA values for cationized proteins and suggest specific mechanisms at cerebral blood vessels that distinguish transport of cationized from noncationized macromolecules. PMID- 1877705 TI - Activation of renal mechanoreceptors increases vasopressin release in rabbits. AB - Electrical stimulation of afferent renal nerves increases plasma vasopressin (AVP) concentration, but the role of these nerves in the control of AVP release is not known. The aim of the present study was to investigate the effect of activation of renal mechanoreceptors and chemoreceptors on plasma AVP concentration in anesthetized rabbits. Intrapelvic pressure was increased to activate renal mechanoreceptors, and the renal pelvis was perfused with 1.0 M NaCl, 0.1 M KCl, and 1.0 M mannitol solutions to activate R2 chemoreceptors. With increased pelvic pressure, plasma AVP concentration increased from 12.4 +/- 3.8 to 36.2 +/- 16.1 pg/ml at 5 min and to 37.4 +/- 16.1 pg/ml at 10 min (P less than 0.01). Plasma renin activity increased from 15.7 +/- 4.0 to 22.1 +/- 3.3 ng.ml 1.2 h-1 (P less than 0.05), but blood pressure and heart rate did not change significantly. Similar increases in plasma AVP concentration occurred during perfusion of the renal pelvis with 1.0 M NaCl (17.6 +/- 8.1 to 53.7 +/- 24.0 pg/ml), 0.1 M KCl (9.2 +/- 2.1 to 39.7 +/- 17.3 pg/ml), and 1.0 M mannitol (27.5 +/- 10.9 to 77.5 +/- 30.8 pg/ml) solutions. However, because pelvic pressure increased by 40-50 mmHg during the perfusions, the experiments were repeated with use of a different perfusion method in which pelvic pressure increased by less than 5 mmHg. Under these conditions, plasma AVP concentration did not change significantly during perfusion with any of the solutions. To determine whether the mechanoreceptor-induced increase in AVP release is mediated by the renal nerves, pelvic pressure was increased in another group of rabbits after renal denervation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877706 TI - Phase response curves to light in young and old hamsters. AB - The phase-shifting effects of 1-h light pulses on the circadian rhythm of locomotor activity were measured in young (less than 12 mo old) and old (greater than 16 mo old) hamsters. Phase response curves (PRCs) for both age groups showed an inactive region [approximately circadian time (CT) 0 through CT12], a delay region (CT12 through CT16), and an advance region (CT16 through CT24) as has been reported for young animals. Significant age group differences in the amplitude of phase shifts were measured, with older animals showing larger shifts limited to the region of the "break point" at CT16. The free-running period of the activity rhythm was measured before the first light pulse; age-related decreases of period length consistent with previous reports were measured. The findings indicate that the response of the circadian clock to the major environmental synchronizing agent, light, is different in old hamsters compared with young adults. PMID- 1877707 TI - Characterization of electroencephalographic state in fetal baboons. AB - Long-term recordings of the electroencephalograms (EEGs) from the non-human fetal primate have been visually scored for state. Data were obtained from three fetuses using recently developed techniques for chronic instrumentation of the pregnant baboon. Seven days or more after surgery, nine chart records of 4-5 h in duration were analyzed. These records were made during an interval in gestation from 143 to 153 days (term = 175 to 185 days). Criteria for differentiation of EEG state were based on the presence (state 1) or absence (state 2) of trace alternant, which is the predominant characteristic of EEG activity during quiet sleep in human preterm and term infants. Two patterns of EEG activity were readily distinguished at both standard (30 mm/s) and compressed (30 mm/min) EEG chart speeds. On a minute-by-minute basis, there was an overall concurrence of 82.9% for EEG state when scored from compressed and standard EEG records. From the compressed records, state 1 was present on average 38.3% of the time, with a mean epoch duration of 15.1 min, while epochs of state 2 averaged 25.9 min. We conclude that at least two EEG states are present at this gestation in the fetal baboon. These two states can be reliably defined visually by scoring methods directly comparable to those used for EEG recognition of sleep states in the human newborn infant. To validate the conclusion that these fetal state assignments based on patterns of EEG activity correspond to sleep states, it will be necessary to determine if the oscillations of other physiological parameters are coherent with these patterns. PMID- 1877708 TI - Glucagon in physiological concentrations stimulates brown fat thermogenesis in vivo. AB - Our aims were to further characterize the stimulatory effect of glucagon on brown fat and to test the hypothesis that physiological levels of hyperglucagonemia would stimulate brown fat thermogenesis. In the first set of experiments, glucagon (1 mg/kg sc twice daily) or vehicle control was administered three times in 26 h. This large dose of glucagon produced increases in GDP binding to brown fat mitochondria. In addition, Scatchard analysis indicated a glucagon-induced increase in number of GDP binding sites without evidence for alteration in binding site affinity. No consistent increase in brown fat mitochondrial GDP binding was produced 2 h after a single injection of glucagon (1 mg/kg). In the second set of experiments, glucagon was administered intraperitoneally by constant osmotic minipump infusion. Glucagon in a dose of 150 micrograms.kg-1.day 1 for 5 days produced significant increases in GDP binding to brown fat mitochondria, whereas glucagon serum levels were increased but stayed within the usual physiological range. A larger dose of glucagon administered by constant infusion virtually eliminated body weight gain over 7 days while significantly increasing nucleotide binding (GDP) to brown fat mitochondria. An important role for glucagon in thermogenic regulation is suggested. PMID- 1877709 TI - Failure to demonstrate that accelerated gastric emptying after VMH lesions is secondary to excess weight gain. PMID- 1877710 TI - Dengue-1 virus envelope glycoprotein gene expressed in recombinant baculovirus elicits virus-neutralizing antibody in mice and protects them from virus challenge. AB - In order to test the feasibility of baculovirus (Autographa californica nuclear polyhedrosis virus, AcNPV) expression vectors for making immunogens against dengue-1 (DEN-1) virus, a portion of the envelope (E) glycoprotein gene of DEN-1 virus was cloned and expressed. The recombinant baculovirus contains 107 nucleotides from the 3' terminus of the DEN-1 matrix (M) gene, which encodes a hydrophobic signal peptide and extends through the first 1, 245 nucleotides of E, terminating 243 nucleotides before the 3' terminus of E. When the recombinant virus was grown in Spodoptera frugiperda cells, about 1 mg of E antigen was made per 10(9) cells. Recombinant E antigen reacted with E protein-specific monoclonal antibodies and stimulated production of DEN-1 virus neutralizing antibody in BALB/c mice. Mice immunized with recombinant E antigen or with heat-inactivated DEN-1 virus were protected significantly against lethal DEN-1 virus challenge. A dose/response effect was observed, with increasing amounts of recombinant antigen leading to increased survival. These results demonstrate the utility of baculovirus for producing immunogens against DEN-1 virus. PMID- 1877711 TI - Efficacy of ivermectin for control of microfilaremia recurring after treatment with diethylcarbamazine. I. Clinical and parasitologic observations. AB - We compared the efficacy of a single dose of ivermectin with that of a standard course of diethylcarbamazine (DEC) for the control of microfilaremia in 60 patients with bancroftian filariasis who had developed recurrent microfilaremia after each of three or more prior treatments with DEC. The study was done as a randomized, double-blind trial. Complete, but in some cases, transient clearance of microfilaremia was observed in both treatment groups. At one year, recurrent microfilaremia was present in seven patients treated with ivermectin and in five treated with DEC. Pretreatment levels of microfilaremia were significantly higher in patients who relapsed within one year after treatment than in those who remained amicrofilaremic. Side effects with both treatments were common, but mild. Febrile reactions were more frequent in the ivermectin group; localized reactions consistent with a flare-up of acute filarial disease occurred mostly in the DEC group. We conclude that ivermectin is an effective and practical alternative to DEC for treatment of recurrent microfilaremia due to bancroftian filariasis. PMID- 1877713 TI - Alveolar hydatid disease of the liver: a report on thirty-nine surgical cases in eastern Anatolia, Turkey. AB - The charts of 39 consecutive patients who underwent surgery between 1979 and 1989 with a diagnosis of alveolar hydatid disease (AHD) of the liver were reviewed. The analysis of these cases from eastern Anatolia, which is the endemic region in Turkey, was undertaken to determine the current experience for AHD lesions. Of these patients, 33 (84.6%) had unresectable disease and the remaining six patients (15.4%) were treated by hepatic resection of the primary lesion. In the unresectable cases, laparotomy with biopsy was the most commonly used surgical procedure (56.4%), followed by tube drainage of the necrotic cavity (18.0%), marsupialization (5.1%), and cystojejunostomy (5.1%). Diagnostic studies and operative findings were useful in detecting the AHD lesions. Differential diagnosis was established mainly by histopathologic examination of a biopsy specimen or resected tissue. Pulmonary metastases were seen in two cases, and mortality occurred due to brain metastases in two other cases. Mebendazole was administered postoperatively to 19 patients with indications for 1) advanced AHD, 2) adjuvant therapy to radical and palliative surgical procedures, and 3) recurrences of disease after hepatic resection. The patients were treated with daily doses of approximately 50 mg/kg for periods of one and six years (median 3.2 years). Encouraging results were obtained in 11 of nineteen patients. Five year survival was seen in 8 of the patients with AHD in this series. There were 18 deaths (46.2%) in our 39 patients. Long-term follow-up was not possible in four cases, and 17 patients (43.6%) were still living. The causes of mortality were advanced AHD in 14 cases, brain metastases in two, and acute myocardial infarction in another two.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877712 TI - Efficacy of ivermectin for control of microfilaremia recurring after treatment with diethylcarbamazine. II. Immunologic changes following treatment. AB - We compared the effect of a single dose of ivermectin with that of a standard course of diethylcarbamazine (DEC) on several parameters of the host's antifilarial immune response in 60 patients with bancroftian filariasis enrolled in a double-blind drug trial. All participants had measurable serum levels of antifilarial antibodies and parasite antigens at the onset of the study. Drug induced clearance of microfilaremia was associated with a temporary increase in HC 11 antigenemia and a decrease in serum levels of antibodies to soluble filarial antigens. Antigenemia progressively declined in patients who remained amicrofilaremic after treatment, but declined and then increased in persons with recurrent microfilaremia. Treatment triggered a sustained increase in serum levels of interleukin-1, tumor necrosis factor, and interleukin-6 in all patients studied. Although ivermectin and DEC are believed to exert their antiparasite activity via different mechanisms, the same pattern of serologic changes was observed in patients treated with either drug. PMID- 1877714 TI - Eosinophil-rich, granulomatous inflammatory response to Plasmodium berghei hepatic schizonts in nonimmunized rats is age-related. AB - Inflammatory responses to Plasmodium hepatic schizonts within the livers of non immunized animals have long been assumed to be initiated only after the parasites have matured and begun to burst. However, recent reports of inflammatory responses around hepatic schizonts suggested a re-examination of this issue. We injected Norway-Brown rats of various ages intravenously with Plasmodium berghei sporozoites and studied subsequent liver histopathology. We found that the ability of these rats to mount an inflammatory response is age-dependent. Young (4 weeks) rats had weak inflammatory responses against hepatic schizonts, whereas older (8-10 weeks) rats mounted a strong response. Older rats had many granulomatous reactions within the liver; eosinophils represented a pioneer component of the cellular infiltrate. There was a reduction in the numbers of surviving hepatic schizonts in the older rats, suggesting that these granulomatous and eosinophilic reactions had effectively destroyed some of the hepatic schizonts. We found clear evidence of inflammatory cells (eosinophils) infiltrating hepatic schizonts as early as 40 hours post-injection with sporozoites, a time well before any hepatic schizonts could have burst within the liver. This presents histological evidence that inflammatory cells can recognize and infiltrate intact hepatocytes containing schizonts in immunologically naive animals. PMID- 1877716 TI - Hypnozoites of Plasmodium simiovale. AB - Hypnozoites of Plasmodium simiovale were detected in liver biopsies from a rhesus monkey (Macaca mulatta) inoculated eight days previously with sporozoites from heavily infected anopheline mosquitoes. The tissue forms, 6 mu in diameter, were found within the cytoplasm of hepatic parenchymal cells by immunofluorescence and restained with Giemsa. This is the first report of latent, pre-erythrocytic stages from an ovale-type relapsing malaria. PMID- 1877715 TI - Infection of Aedes albopictus and Aedes aegypti mosquitoes with dengue parent and progeny candidate vaccine viruses: a possible marker of human attenuation. AB - Dengue (DEN-1) and DEN-4 parent (P) and progeny candidate vaccine (CV) viruses were compared in their abilities to infect and to replicate in Aedes aegypti and Aedes albopictus mosquitoes. The DEN CV clones were temperature sensitive (ts) and had small plaque morphology. The DEN-1 and DEN-4 CV viruses differed in their ability to infect, to replicate in, and to be transmitted by mosquitoes. The DEN 1 CV virus was not attenuated for the vector mosquitoes; oral infection rates with the CV virus were as high as or higher than the P virus, and the CV virus replicated efficiently in mosquitoes after oral infection. The DEN-4 CV virus was attenuated; it was less efficient than its P virus in infection and replication in mosquitoes. Thus, the ts phenotype and small plaque morphology are not reliable biological markers for prediction of vector attenuation. Similar results were reported by others for attenuation in man and monkeys. These studies with DEN-1 and DEN-4 viruses, and previously reported studies with DEN-2 virus and with DEN-3 virus suggest that vector and vertebrate host attenuation are genetically linked. Thus, vector attenuation may be a biological marker for human attenuation. PMID- 1877717 TI - Anopheline ecology and malaria infection during the irrigation development of an area of the Mahaweli Project, Sri Lanka. AB - A study on adult anopheline ecology and malaria vector incrimination was carried out from 1986 to 1989 during irrigation development in an area of the Mahaweli Project in eastern Sri Lanka. Eleven potential vector species were collected resting indoors or by using human or bovid bait, and from light trap catches. Overall, Anopheles vagus (Donitz), An. annularis (van der Wulp), and An. subpictus (Grassi) were the most prevalent, and An. culicifacies (Giles) and An. barbirostris (van der Wulp) were the least prevalent species. The abundance of An. aconitus (Donitz), An. jamesii (Theobald), An. pallidus (Theobald), and An. subpictus increased after irrigation development, while An. annularis, An. barbirostris, An. culicifacies and An. varuna (Iyengar) decreased. Populations of An. nigerrimus (Giles), An. tessellatus (Theobald), and An. vagus did not change substantially. Seven species were infected with malaria parasites, as determined by enzyme-linked immunosorbent assays (ELISA) done on mosquito head-thorax triturates. The main species involved were An. annularis, at peak abundance during the 1986-1987 period of development leading to the onset of irrigation, and An. subpictus, during times of seasonal abundance in the post-irrigation period of 1988 to 1989. Although occurring at low abundance, An. culicifacies was involved in malaria transmission irregularly throughout the study period. While there was strong ELISA-based evidence implicating An. subpictus as a major post irrigation vector, confirmation of its vector status must await dissection and ELISA-based evidence of P. vivax and P. falciparum sporozoite infection rates in salivary glands. PMID- 1877718 TI - Strain specificity in the liver-stage development of Plasmodium falciparum in primary cultures of new world monkey hepatocytes. AB - Primary cultures of Aotus and Saimiri monkey hepatocytes were infected with sporozoites of the Plasmodium falciparum NF 54 strain from mosquitoes fed on gametocyte cultures, and with sporozoites of the P. falciparum Santa Lucia strain from mosquitoes fed on an infected Aotus monkey. After 4-8 days, one exoerythrocytic (EE) parasite per 30,000 sporozoites was detected in one of three experiments performed with the P. falciparum NF54 strain. However, numerous EE parasites were detected in Aotus and Saimiri cells infected with sporozoites of the P. falciparum Santa Lucia strain. At day 6, most of the parasites contained several hundred nuclei, and were morphologically similar to those previously described in vivo using light or electron microscopy. A monoclonal antibody directed against the repeat region of the circumsporozoite protein of P. falciparum labeled the plasma and parasitophorous vacuole membrane of five-day old EE parasites by immunoelectron microscopy, thus supporting previous observations by immunofluorescence indicating that the CS protein persists throughout the EE development of P. falciparum. These results demonstrate that liver stages of P. falciparum can be obtained in Aotus and Saimiri monkey cells, they also suggest a parasite strain specificity for hepatocytes. PMID- 1877719 TI - Prevalence of antibodies to spotted fever group rickettsiae in dogs from southeastern Australia. AB - Recent epidemiologic data suggests that Rickettsia australis, the cause of Queensland tick typhus, is present in southeastern Australia. In order to further confirm this observation, a canine serosurvey was undertaken to determine if naturally occurring antibodies were present in pet and farm dogs from this newly recognized endemic area. Thirty-five of 312 surveyed dogs (11.2%) had indirect immunofluorescent antibody titers of 1:64 or greater against R. australis antigen. Positive control sera were obtained from two dogs experimentally inoculated with R. australis. One of these dogs was serially sampled and a rickettsemia could not be documented. None of 26 control sera obtained from dogs from South Australia, New Zealand, western Victoria, or North Carolina had antibody titers greater than or equal to 1:64. These results suggest that spotted fever group rickettsiae are present in Southeastern Australia. PMID- 1877720 TI - Enterobius egg granuloma of the vulva and peritoneum: review of the literature. AB - Two cases of Enterobius granuloma containing eggs only are reported. The first case involved the vulva, where no such granuloma has been reported previously. The coexistence of peritoneal granuloma and rectal adenocarcinoma in the second case suggests the possibility of direct penetration of the damaged colonic wall by the parasite, as emphasized by several previous reports of neoplastic involvement and perforation of the intestinal wall in cases of ectopic infections. The diagnostic criteria of Enterobius eggs granuloma, which might be a diagnostic dilemma for pathologists who are not familiar with such criteria, are described herein. PMID- 1877721 TI - Standard and reduced doses of mefloquine for treatment of Plasmodium falciparum in Tanzania: whole blood concentrations in relation to adverse reactions, in vivo response, and in vitro susceptibility. AB - Fifty-three asymptomatic Tanzanian school children with 400-31,000 asexual Plasmodium falciparum parasites/microliter of blood were given standard, one half, one-quarter, or one-eighth of the recommended mefloquine treatment dose of 25 mg base/kg body weight. Mefloquine and main metabolite concentrations were determined in 100 microliters of capillary blood using a high performance liquid chromatographic method. In the standard, one-half, and one-quarter dose groups, all children cleared the parasites within three days after treatment. Reappearance was noted in one of the children in the one-quarter dose group during 49-56 days of followup. Among the children given one-eighth of a dose, two had an RII response and four had an RI response with early recrudescence. All 24 hour in vitro micro-tests (n = 30) showed full susceptibility for mefloquine. Adverse gastrointestinal reactions were reported by eight children on the first day after treatment, four of whom had been given a standard dose. These children had higher mefloquine concentrations one day after treatment than the other children in this group (P less than 0.05). In the standard dose group (n = 13), the area under the curve of capillary whole blood concentrations of mefloquine versus time was 52.4-112.1 mumol/liter x days. The highest concentration on day 1 was 2.75-7.20 mumol/liter and the median terminal half-life was 17.4 days. The highest concentrations of the main metabolite were observed 1-2 weeks after treatment and the median half-life was 18.9 days. The concentrations in the other groups were approximately proportional to those in the standard dose group both for mefloquine and the metabolite.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877722 TI - Pre-travel health, immunization status, and demographics of travel to the developing world for individuals visiting a travel medicine service. AB - It is estimated that five million Americans will travel to the developing world over the next year. This study examines the demographic profile, past medical and immunization history, itinerary, and reason for travel of 2, 445 travelers to the developing world seen at a travel medicine service from 1984 through 1989. The travelers age ranged from three months to 85 years (mean age 43). A chronic medical condition was reported by 654 (27%). Four percent of all travelers were intolerant of sulfonamides, and 9% had contraindications to mefloquine for malaria prophylaxis. Many travelers were due to receive the primary series or updatings of routinely recommended immunizations: 43% for tetanus/diphtheria, 55% of those born after 1956 for measles, and 70% for polio if their travel itinerary included a polio risk. Most travel (71%) was for vacations, 13% was for teaching or study, 11% for business, and 5% for missionary activities. The median duration of travel was 21 days; 5% traveled for more than one year. While over 150 countries were visited, 52% of all travel was to 10 countries in East Africa, the Indian subcontinent, the Far East, and South America. Information about the epidemiology of travel to the developing world can help physicians and travel medicine services develop more effective preventive measures for travelers. PMID- 1877723 TI - Species-diagnostic differences in a ribosomal DNA internal transcribed spacer from the sibling species Anopheles freeborni and Anopheles hermsi (Diptera:Culicidae). AB - Approximately 460 base pairs (bp) of DNA sequence that included the second internal transcribed spacer (ITS2) and some flanking 5.8S and 28S ribosomal RNA coding regions were compared between the two closely related and morphologically indistinguishable mosquito species Anopheles freeborni and A. hermsi and a third related species, A. occidentalis. Sequences were determined from 14 clones of polymerase chain reaction (PCR)-amplified DNA obtained from four colonies of A. freeborni, two colonies of A. hermsi, and one individual A. occidentalis. Four clones showed independent single bp differences from the consensus for the relevant species. Eleven sites differed between the consensus sequences of A. hermsi and A. freeborni; 28 sites differed between A. hermsi and A. occidentalis. With the exception of a single bp mismatch in the 5.8S and two single bp mismatches near the undetermined junction of the ITS2 and 28S regions, all differences were confined to the ITS2 region. A PCR-based species-diagnostic assay for the cryptic species A. hermsi and A. freeborni was developed; it uses four synthetic oligonucleotides, two derived from areas of interspecies sequence difference in the ITS2, and two derived from highly conserved regions in the flanking coding sequences. Small amounts of mosquito DNA amplified in the presence of these four primers produce fragments of diagnostic size for each species: 900 bp for A. freeborni, 350 bp for A. hermsi, and approximately 1.2-1.4 kb for various other Anopheles species tested. We believe that this general approach to the development of species-diagnostic assays can be extended easily to other complexes of closely related, morphologically indistinguishable species. PMID- 1877724 TI - Acetate metabolism: new mysteries from old data. PMID- 1877725 TI - Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome. AB - Acute ethanol administration (3 g/kg twice a day) to pregnant mice, from the 9th thru the 11th day of gestation, resulted in hypomethylation of fetal deoxyribonucleic acid (DNA). Nuclei isolated from the fetuses of the ethanol treated mice had lower levels of methylase activity relative to controls even in the presence of excess S-adenosylmethionine, which serves as the methyl donor for the enzyme DNA methyltransferase. Acetaldehyde, at concentrations as low as 3 to 10 microM, inhibited DNA methyltransferase activity in vitro. Since DNA methylation is thought to play an important role in the regulation of gene expression during embryogenesis, ethanol-associated alterations in fetal DNA methylation may contribute to the developmental abnormalities seen in the fetal alcohol syndrome. PMID- 1877726 TI - Chronic tolerance and sensitization to alcohol in sons of alcoholics. AB - In view of conflicting results concerning differences between sons of alcoholics and sons of nonalcoholics in response to a single alcohol challenge (with a given dose), we exposed these high and low risk groups to several sessions in which they drank alcohol at the same dose in order to measure the development of chronic tolerance or sensitization with repeated doses. Sons of alcoholics and sons of nonalcoholics received a moderate dose of alcohol (0.5 g/kg) in three sessions with alcohol, followed by a placebo session. Sons of alcoholics developed reverse tolerance or chronic sensitization to repeated dosings of alcohol in finger pulse amplitude, while sons of nonalcoholics did not. Sons of alcoholics failed to show chronic tolerance in skin conductance and finger temperature, while sons of alcoholics did show the development of tolerance. Sons of alcoholics demonstrated greater motor activity throughout the sessions, both before and after alcohol. These results indicate that high and low risk groups differ in terms of their developmental adaptation to alcohol, as well as in the temperamental trait of behavioral activity. PMID- 1877727 TI - Ro15-4513 attenuates the consumption of ethanol in deprived rats. AB - This research investigated the effects of Ro15-4513 (Ro15), a partial inverse benzodiazepine agonist, on the drinking behavior of 23-1/2 hr fluid deprived rats. Water-deprived rats were maintained on a two-bottle regimen of a saccharin ETOH solution along with tap water available for 30 min/day for several days. Following this acclimation period, animals were pretreated with either Ro15 (1.0, 2.5, and 5.0 mg/kg) or Tween-80 vehicle injections. Pretreatment with Ro15 at all doses tested resulted in a significant reduction of the saccharin-ETOH solution; however, Ro15 did not alter the rats' consumption of water. The effects of Ro15 on general fluid consumption was investigated in Experiment 2. Following acclimation to a two-bottle regimen of a saccharin-solution and tap water 30 min/day, naive animals were pretreated with Tween-80 vehicle or Ro15 injections. Ro15 failed to alter saccharin or water consumption. The results of this study support previous reports suggesting that Ro15 attenuates the oral consumption of ETOH; however, this effect does not appear to be due to a general suppression of fluid intake. PMID- 1877728 TI - Reduced cerebral grey matter observed in alcoholics using magnetic resonance imaging. AB - Twenty-eight chronic alcoholics and 36 age- and sex-matched non-alcoholic controls were examined with magnetic resonance imaging and brain morphometric analyses. Results confirmed large increases in subarachnoid cerebrospinal fluid (CSF) volume and mild ventricular enlargement in the alcoholics and revealed associated volume reductions of localized cortical and subcortical cerebral structures. Volume losses in the diencephalon, the caudate nucleus, dorsolateral frontal and parietal cortex, and mesial temporal lobe structures were the most prominent. Significant correlations between increments in cortical and ventricular CSF and decrements in the volume of cortical and subcortical grey matter were noted. Although there was little evidence for relationships between performance on neuropsychological tests and volume of grey matter structures, significant correlations between some cognitive measures and subcortical and cortical fluid volumes were found. The parallels between this pattern of affected structures and recent neuropathological findings are discussed. PMID- 1877729 TI - Changes with age in the proliferative response of splenic T cells from rats exposed to ethanol in utero. AB - The fetal alcohol syndrome is associated with altered immunity. Several laboratories have confirmed that rodents exposed to ethanol in utero demonstrate both diminished proliferative responses of T cells to mitogens and diminished proliferative responses of T-blast cells to human recombinant interleukin 2 (rIL2). We examined the developmental time course of these altered immune responses by testing the immune function of in utero ethanol-exposed rats at various ages. We found that while diminished splenic T cell proliferative responses could not be detected at 2 weeks, they were present at 6 weeks after birth and suppression was maximal at 6 weeks and 3 months. Thereafter, at 5 and 7 months, the altered immune responses gradually declined and normalized at 8 months of age. Thus, both altered T cell mitogenesis and the blunted IL2-induced proliferative response of T-blast cells could serve as biomarkers of fetal exposure to ethanol. PMID- 1877730 TI - Trauma in cirrhosis: an indicator of the pattern of alcohol abuse in different societies. AB - While some morbidities associated with the excessive use of alcohol are related to the total amount of alcohol consumed--cirrhosis being an example--other pathologies, such as trauma and those of psycho-social origin, are mainly related to the frequency of acute alcoholic intoxication rather than to the total amount consumed. The balance between these two types of alcohol-associated morbidities can provide an indication of the relative frequency of intoxication, and thus of the pattern of alcohol abuse in a population. Since trauma is highly associated with acute alcoholic intoxication, the prevalence of bone fractures was determined in cirrhotics in nine countries. The prevalence of rib and vertebral fractures on routine chest x-rays showed a 17-fold variation in the different countries, from 2% and 6% in Spain and Italy to 30% and 34% in Canada and the USA, suggesting marked differences in the pattern of alcohol abuse to intoxication. Conversely, the prevalence of cirrhosis is twice as high in Spain and Italy than in Canada and the USA. A strong positive correlation between per capita consumption and cirrhosis mortality (r = 0.86; p less than 0.01) exists among the nine countries studied, while the correlation between per capita alcohol consumption and the prevalence of trauma is not statistically significant (r = 0.40). Supporting a strong association between trauma and alcoholic intoxication, the prevalence of trauma was found to be highly correlated: r = 0.88, p less than 0.002, with the degree of concern for the psycho-social consequences of alcohol abuse in the different countries. Data indicate that trauma can be used as an objective indicator to assess the pattern of alcohol abuse in a population. PMID- 1877731 TI - Personality stability and adolescent substance use behaviors. AB - Several personality needs have consistently been identified as placing adolescents at heightened risk for the relatively intensive use of alcohol and other drugs. At the same time, little is known about the natural history of personality change during adolescence as it relates to substance use behaviors. Yet, this question is of clear importance to our understanding of personality risk factors for substance use because personality needs appear less temporally stable during adolescence than later in the life span. In this study, we use prospective longitudinal data to investigate the relation of high-risk personality needs to substance use in two groups of adolescents: those who maintained a temporally stable personality need structure across 3 years and those who showed considerable changes in personality needs during the same time interval. Subjects were 12, 15, or 18 years old at the first test time and 15, 18, or 21 years old, respectively, at the second test time. For subjects of both sexes, only those who maintained a temporally stable, low-risk personality profile showed quite conservative substance use patterns across time compared with all others. Generalized personality changes were linked to more intensive substance use behaviors in males, especially among those who had high levels of risky personality needs at the first test time. In contrast, personality change, per se, did not appear as relevant to females' alcohol and other drug use behaviors until combined with information regarding their level of high-risk personality needs. The results are discussed in terms of their implications for prevention and future research. PMID- 1877732 TI - Blood pressure dysregulation associated with alcohol withdrawal. AB - Alcoholics' blood pressures (BP) are typically elevated during withdrawal. Do such elevations predict future blood pressure dysregulation or are they simply a transitory effect of alcohol toxicity? Thirty-two patients admitted to the hospital for alcohol detoxification were tested to examine the relationship between admission BP and response to isometric handgrip administered 4 to 5 days (session 1) and 3 to 4 weeks (session 2) postdetoxification. Alcoholics were divided into three groups based on admission BPs: Hypertensive (HT, greater than or equal to 160/95 mmHg), Borderline Hypertensive (BHT, 140/90-159/94 mmHg), and Normotensive (NT, less than 140/90 mmHg). In sessions 1 and 2, the groups no longer differed on resting BP or heart rate (HR) but did differ on BP and HR response to handgrip: Compared with the NT group, the HT and BHT groups had greater rises in systolic and diastolic BP and HR. There was a trend for HT alcoholics to report a positive parental history of hypertension (91%) compared to BHT and NT alcoholics (64% and 60%, respectively), suggesting the existence of premorbid factors to this exaggerated cardiovascular response. Further, alcohol consumption, based on a quantity-frequency index, was significantly higher in the HT group than in the NT group. The results suggest that transitory elevations in blood pressure observed during alcohol withdrawal may predict future BP abnormalities. PMID- 1877733 TI - Ethanol inhalation and dietary n-6, n-3, and n-9 fatty acids in the rat: effect on platelet and aortic fatty acid composition. AB - The effects of 18-carbon n-6, n-3, and n-9 fatty acid diets and ethanol exposure on the fatty acyl composition of platelets and vascular tissue were examined. An experimental design was devised to control the dietary content of 18-carbon fatty acids. The levels of 18:3n6, 18:3n3 and 18:1n9 were varied by a formulation of dietary oils which contained similar proportions of 18:2n6. Male Sprague-Dawley rats were fed a purified diet containing 11% by weight of either borage oil (BOR) rich in 18:3n6, linseed/safflower oil (LSO) rich in 18:3n3, or sesame oil (SES) rich in 18:1n9 for 7 weeks and exposed to ethanol vapors by means of inhalation for the final 6 days of the dietary regimen. Moderate blood ethanol levels of 118 +/- 6.6 mg/dl were obtained. Total lipids were extracted from platelets and aortae, and the fatty acid distributions were analyzed by gas chromatography. BOR feeding resulted in increases in the proportion of n-6 fatty acids (18:3n6, 20:3n6, 20:4n6) in platelets and aorta. Animals fed the LSO diet had increased levels of n-3 fatty acids (18:3n3, 20:5n3, 22:6n3). The SES-based diet resulted in an increase in 18:1n9 in both aorta and platelets. Following ethanol exposure alone, the most marked change in the fatty acid profile was a decrease in 20:4n6 in the platelet. This effect was not observed in rats supplemented with BOR. No significant changes were observed in the aortic fatty acid content at this level of ethanol exposure. The results suggested that, in the rat, a diet enriched with BOR effectively prevented ethanol-induced alterations in platelet fatty acid composition. PMID- 1877734 TI - Estimation of blood alcohol concentrations in young male drinkers. AB - This research examined individual differences in the ability to self-monitor the effects of alcohol. Thirty-nine male subjects consumed 0.75 ml/kg alcohol and estimated their blood alcohol concentrations (BACs) at peak BAC and on the ascending and descending limbs of the blood alcohol curve. Family history of alcohol dependence did not affect the accuracy of estimation of BACs. Subjects who reported lower levels of subjective intoxication underestimated their BACs more than did subjects who reported higher levels of subjective intoxication. Subjects with less behavioral impairment underestimated their BACs more than subjects with greater behavioral impairment on the ascending limb of the blood alcohol curve. Accuracy was better on the ascending limb compared with peak BAC and the descending limb, and accuracy became worse over time on the descending limb. It appears that cues to the effects of alcohol rapidly become unavailable on the descending limb, which may contribute to decisions concerning further alcohol consumption and driving after drinking. PMID- 1877735 TI - Alterations of ATP levels and of energy parameters in the blood of alcoholic and nonalcoholic patients with liver damage. AB - Blood adenine nucleotides were determined in patients with alcoholic and non alcoholic liver diseases. They included patients with alcoholic hepatitis (AH), alcoholic liver cirrhosis (ALC), non-alcoholic liver cirrhosis (NALC), and amoebic liver abscess (ALA) (28 patients). A decrease of 28% to 39% in blood ATP levels was observed among the patients with AH and the cirrhotic groups, respectively (p less than 0.05), whereas no significant changes in blood ATP levels were detected in the ALA group. Although total blood adenine nucleotides were significantly diminished in AH, ALC, and NALC groups, the AH patients retained their energy relationships within normal range. On the other hand, the cirrhotic groups, independently of their etiology, failed to maintain an adequate ATP/ADP ratio, energy charge, and phosphorylation potential in the blood, suggesting a decreased energy availability in their blood cells. Nevertheless, the mechanism involved in these effects remains to be elucidated, a failure of the damaged liver to supply purines to extra-hepatic tissues might be a major event altering the blood energy parameters. PMID- 1877736 TI - In vivo microdialysis study of brain ethanol concentrations in rats following oral self-administration. AB - Using intracerebral microdialysis, the time-course of ethanol absorption was determined in the striatum of rats after oral self-administration of an ethanol solution. Microdialysis samples were collected every 10 min for 1 hr before and 1 hr after consumption of ethanol over a 5-min period. Substantial levels of ethanol were detected in the brain in the first sample taken after self administration although these levels did not correlate with the amount of ethanol consumed. Striatal ethanol levels reached maximum or near maximum by the second sample and remained constant for the time points between 20 and 60 min; at these times, brain ethanol levels correlated significantly with the amount consumed. This study demonstrates that oral consumption of ethanol leads to measurable brain levels within a relatively short time. Results suggest that experimental animals may experience the central effects of ethanol during the course of drinking and this could play a role in alcohol preference or avoidance behavior. PMID- 1877737 TI - Individual mood profiles in alcohol withdrawal. AB - Daily self-reports of moods, using a Swedish Mood Adjective Check List with six bipolar dimensions, were performed in patients with alcohol dependence. One group (n = 13), consisting of inpatients in late withdrawal at a home for addicts, was studied for 6 weeks; another group (n = 12), consisting of outpatients in full remission, was studied for 1 week. The results of the ratings on the check-list were used to test a statistical model for its capacity to describe the individual courses of mood states during the recovery process. Time Series Analysis revealed that the individual courses of moods fitted an autoregressive statistical model and could thereby be summarized in numerical measures for individual baselines, amplitudes, and lengths of recovery. Such individual profiles of the alcohol recovery process, may be useful for both clinical and research purposes, making it possible, for instance, to predict points in time for an individual's recovery with respect to his total well-being, as well as the various dimensions of his mood states. PMID- 1877738 TI - A revised conservative estimate of the incidence of FAS and its economic impact. AB - We have conducted a new analysis of the incidence of fetal alcohol syndrome (FAS) and its economic impact based on prospectively gathered data of consecutive pregnancies. This more conservative analysis reflects our concern over possible inclusion of "false positives" in our previous estimate and now puts the overall rate in the western world at 0.33 cases per 1000. The estimate among whites is 0.29 per 1000 compared with 0.48 per 1000 for blacks. We did not include estimates for native Americans owing to the absence of prospectively gathered data on FAS for this group. Retrospective studies suggest larger disparities. Both prospective and retrospective studies may be influenced by examiner bias especially for minorities since minorities are often evaluated against standards derived from whites. Based on our estimates and the number of black and white children born each year, we estimate that about 1200 children are born with FAS each year in the United States. This is a probable lower limit based on considerations of ascertainment and absence of relevant information for other minorities such as native Americans. In calculating economic costs, we have now adjusted our estimates to take into account costs that would be incurred whether cases were FAS or not, and also have now included estimated costs for anomalies in FAS cases not considered in previous estimates. Based on these considerations, we now estimate the incremented annual cost of treating this disorder at $74.6 million. About three-quarters of this economic burden is associated with care of FAS cases with mental retardation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877739 TI - Suppression of immune responsiveness: sex differences in prenatal ethanol effects. AB - Exposure to ethanol in utero results in changes in the offspring's developing immune system, including thymus lymphocyte subpopulation shifts and functional lymphocyte changes that persist in adult animals. The present study was designed to define further the extent of changes in the immune system that result from fetal ethanol exposure and to compare effects in male and female offspring. In adulthood, male and female offspring from Sprague-Dawley dams fed an ethanol containing liquid diet (alcohol, A), an isocaloric liquid control diet (pair-fed, PF), or laboratory chow and water (control, C) during pregnancy were tested for several measures of immune competency. Prenatal ethanol exposure differentially affected male and female offspring. Fetal ethanol-exposed males exhibited a decrease in thymocyte number as well as a decreased splenic lymphocyte proliferative response to the T-cell mitogen, concanavalin A (Con A), with a concomitant decrease in recoverable blast cells, when compared with PF and C males. Further, the defect in T-cell proliferation of A males was not due to an inability to produce the critical growth factor, interleukin-2 (IL-2), but to an inability of lymphoblasts to utilize exogenous IL-2. Fetal ethanol-exposed females showed some suggestion of lower thymocyte counts and decreased splenic T cell proliferative responses to Con A compared to PF and C females. For most of the immune measures, however, no significant differences occurred among A, PF, and C females. In utero ethanol exposure did not significantly alter spleen cell counts or IL-2 production, splenic B-cell proliferation to bacterial lipopolysaccharide (LPS), or thymocyte response to IL-2 in animals of either sex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877740 TI - Disulfiram implant: a double-blind placebo controlled follow-up on treatment outcome. AB - Seventy-six alcohol-dependent patients participated in a study of the clinical effect of implanted disulfiram (DS). The patients were randomized to a DS group (n = 40), receiving a subcutaneous abdominal implantation of 10 x 100 mg DS tablets and a placebo group (PL group) receiving an implantation of 9 x 100 mg calcium phosphate tablets together with one calcium phosphate tablet containing 1 mg DS. Both groups believed they were receiving DS. At admission there was no significant difference between the DS and PL groups with regard to demographic characteristics, psychosocial adjustment, drinking variables, medical disorders, or laboratory results. After a study period of approximately 300 days, 63 patients (33 DS; 30 PL) were assessed using a battery of tests. There was no significant difference between the groups with regard to reduction in average alcohol consumption, number of days to the first alcohol intake after implantation, or level of psychosocial function. Nevertheless, both groups reduced their ethanol consumption significantly, probably due to the psychological deterrent effect. The DS implant did result in a significantly higher incidence of wound complications. This study does not support the idea that a 1-g DS implant has any significant clinical effect different from the implant containing only 1 mg DS (placebo). PMID- 1877741 TI - Response of three hormones to diazepam challenge in sons of alcoholics and controls. AB - This study evaluates the hypothesis that the decreased reaction to ethanol reported for sons of alcoholics will also be observed following infusions of a benzodiazepine. The investigation compared 37 men who were family history positive for alcoholism with 37 family history negative controls on postinfusion levels of cortisol, prolactin, and growth hormone following 0.12 and 0.20 mg/kg of diazepam given IV over 7 minutes. The results demonstrated no evidence of a decreased response for the sons of alcoholics on the levels of these three hormones. PMID- 1877742 TI - Vitamin B12 and folate status in rats after chronic administration of ethanol and acute exposure to nitrous oxide. AB - The chronic administration of ethanol or brief exposure to nitrous oxide (N2O) decreases the activity of hepatic methionine synthase and disrupts normal metabolic processes that require folate and vitamin B12. This combination of drugs has clinical relevance since alcoholic patients often require surgery and receive N2O as a component of their anesthetic. To assess this clinical problem using a rodent model, rats were given a liquid ethanol diet (35% of calories as ethanol) and control rats were pair-fed a liquid diet with carbohydrate substituting for the caloric content of ethanol. After receiving liquid diets for 6 weeks, rats were exposed to 60% N2O/40% O2 for 6 hr. Urinary excretions of formic acid and formiminoglutamic acid (FIGLU) were used as indirect markers of folate status. In both the ethanol-fed and control groups, excretion of formic acid and FIGLU markedly increased the first day after N2O and returned towards background values by the second day after N2O exposure. Ethanol treatment alone decreased methionine synthase activities in liver, but not kidney or brain. Exposure to N2O further decreased methionine synthase activities, and recovery of methionine synthase activity after N2O occurred over a period of 4 days at the same rate in both the ethanol-fed and control groups. Ethanol treatment for 6 weeks combined with acute exposure to N2O did not deplete the rats of vitamin B12 in blood, liver, kidney, or brain. We conclude that in this animal model, chronic treatment with ethanol does not markedly exacerbate the disturbances in folate/vitamin B12 metabolism caused by brief exposure to N2O. PMID- 1877743 TI - Plasma norharman (beta-carboline) levels are elevated in chronic alcoholics. AB - Based on the hypothesis that condensation products of neurotransmitters with aldehydes are involved in the pathogenesis of alcoholism, aromatic beta carbolines (norharman and harman) were measured in the blood plasma of alcoholics and nonalcoholics. The identity of the extracted compounds was confirmed by various elution conditions of the high performance liquid chromatography (HPLC), newly developed radioreceptor assays, and the mass spectrum of norharman. The levels of norharman and harman in nonalcoholics were unchanged after a load with ethanol (1 g/kg body weight). The norharman levels of the alcoholics were significantly higher than that of the nonalcoholic controls (99.5 +/- 26.6 pg/ml vs. 26.9 +/- 10.7 pg/ml; p less than 0.001) and did not change significantly during a 3-week detoxication period. In the subgroup of alcoholics with delirium or hallucinosis, a slight increase of norharman during detoxication could be detected while in alcoholics with vegetative withdrawal symptoms norharman levels dropped slightly over time (p = 0.07). No difference was found with respect to harman between nonalcoholics and alcoholics. These results suggest disturbed regulatory processes in the formation and/or metabolism of norharman in alcoholics. Further investigations are needed to reveal a possible marker function of norharman in alcoholic patients. PMID- 1877744 TI - Inhibition of retinoic acid synthesis and its implications in fetal alcohol syndrome. PMID- 1877745 TI - Hypothesis: prenatal ethanol-induced birth defects and retinoic acid. AB - A hypothesis is presented to explain the biochemical basis of ethanol-induced birth defects. Prenatal ethanol exposure causes central nervous system and limb abnormalities in humans and in animals. Retinoic acid and didehydroretinoic acid are known to play an important role in the central nervous system and limb developments. Ethanol is known to inhibit the formation of retinoic acid from retinol and deplete hepatic retinoid levels. It is hypothesized that ethanol reduces the levels of retinoic acid in the developing embryo either by inhibiting conversion of retinol to retinoic acid and/or by depleting the level of retinol, thereby causing central nervous system and limb abnormalities. PMID- 1877746 TI - A hypothetical mechanism for fetal alcohol syndrome involving ethanol inhibition of retinoic acid synthesis at the alcohol dehydrogenase step. AB - Ethanol acts as a teratogen causing brain, craniofacial, and limb abnormalities in those suffering from fetal alcohol syndrome. Normal embryonic development of the vertebrate nervous system and limbs has recently been shown to be governed by retinoic acid, the active form of vitamin A. Retinol dehydrogenase is an enzyme needed to convert vitamin A (retinol) to retinoic acid, a molecule that specifies embryonic pattern formation by controlling gene expression. Ethanol acts as a competitive inhibitor of the retinol dehydrogenase activity attributed to mammalian alcohol dehydrogenase (ADH), an enzyme that uses both retinol and ethanol as substrates. An hypothesis is presented in which many of the abnormalities observed in fetal alcohol syndrome may be caused by high levels of ethanol acting as a competitive inhibitor of ADH-catalyzed retinol oxidation in the embryo or fetus. This would presumably result in a reduction of retinoic acid synthesis in embryonic tissues such as the nervous system and limbs that require critical levels of this molecule to specify spatial patterns. PMID- 1877747 TI - Selectivity of membrane electrodes based on derivatives of dibenzyltin dichloride. AB - Selectivity properties are established for membrane electrodes prepared by incorporating bis(p-methylbenzyl)tin dichloride, dibenzyltin dichloride, and bis(p-chlorobenzyl)tin dichloride in plasticized polymer membranes. These electrodes display an unusually high level of selectivity for dibasic phosphate over many common anions. Electrodes prepared with the p-chloro derivative possess the best detection limit and the highest degree of selectivity for phosphate. Selectivity coefficients are calculated for phosphate relative to the following groups of anions: salicylate, benzoate, thiocyanate, iodide, nitrate, bromide, chloride, acetate, fluoride, pyrophosphate, arsenate, adenosine 5'-cyclic monophosphate, adenosine 5'-monophosphate, adenosine 5'-diphosphate, and adenosine 5'-triphosphate. Tin-carbon hyperconjugation within the organotin compound is hypothesized to be critically important in the selective response to phosphate. Enhancement of tin-carbon hyperconjugation by increasing the electron withdrawing power of substituents on the benzyl ring is predicted to provide even higher levels of selectivity for phosphate. PMID- 1877748 TI - On-column sample gating for high-speed capillary zone electrophoresis. AB - High-speed zone electrophoresis in a fused-silica capillary is described. Elevated electric fields and short capillary lengths allow a mixture of fluorescein isothiocyanate (FITC) labeled amino acids to be separated in times as short as 1.5 s. Formation of the analyte zone at the head of the capillary is controlled by laser-induced photolysis of a tagging reagent. This gating procedure allows rapid and automated introduction of sample into the capillary. Ultimately, Joule heating of the buffer limits the speed and efficiency of the separation. PMID- 1877749 TI - Sample gating in open tubular and packed capillaries for high-speed liquid chromatography. AB - A new liquid chromatography instrument is described that employs small-diameter capillary columns and an optically controlled sample gating procedure to separate a mixture of fluorescein isothiocyanate (FITC) labeled amines in as few as 6 s. Efficiency of the separation, expressed as the number of theoretical plates, is observed to increase linearly with column length and thus analysis time. The combination of short analysis time and automated sample introduction allows signal averaging to be used to enhance the precision of the measurement. PMID- 1877750 TI - Determination of molecular weight distributions of tert-octylphenol ethoxylate surfactant polymers by laser desorption Fourier transform ion cyclotron resonance mass spectrometry and high-performance liquid chromatography. AB - Triton polymers are commercial surfactants whose molecular weight distributions are conventionally determined by means of high-performance liquid chromatography (HPLC). However, in the case of the important octylphenol ethoxylates [p-C8H17 C6H4-O-(CH2CH2O)n-H], HPLC cannot resolve individual oligomers of high molecular weight Triton surfactants (e.g., greater than 2000 u or so; u = unified atomic mass unit). In this paper, we show that laser desorption Fourier transform ion cyclotron resonance mass spectrometry (LD/FT/ICR/MS) provides a simple and accurate measure of such Triton surfactant molecular weight distributions up to at least 3500 u, based on a single-shot laser pulse measurement of a few seconds duration. Comparison of LD/FT/ICR/MS and HPLC molecular weight distributions of low molecular weight surfactants shows that laser desorption/ionization produces minimal fragmentation and thus offers an accurate measure of the relative abundances of the neutral oligomers, without the need for prior chromatographic separation of the components. Moreover, for all Triton polymer molecular weight distributions (700-3000 u), LD/FT/ICR/MS provides much more highly resolved profiles of oligomer relative abundances. Finally, LD/FT/ICR/MS reveals the presence of poly(ethylene oxide) side products of the polymerization process, which are not observed by HPLC with conventional ultraviolet absorption detection. PMID- 1877751 TI - Quantitative retention-biological activity relationship study by micellar liquid chromatography. AB - In a previous paper, the usefulness of micellar liquid chromatography (MLC) in predicting octanol-water partition coefficients of organic compounds was reported. This paper is the first successful report of a quantitative retention activity relationship study using the retention factor in MLC for predicting the biological activity of a group of phenolic compounds. Excellent correlation was obtained between the capacity factor in MLC and the bioactivity (measured as log 1/C, where C is the 50% inhibitory growth concentration) of 26 para-substituted phenols. A single MLC retention parameter is capable of describing the bioactivity of phenols, while three conventional molecular descriptors (log P(ow), pKa, and R) are needed to achieve a similar correlation. This indicates that both hydrophobic and electronic interactions are incorporated in a single MLC retention parameter, which is due to the amphiphilic nature of surfactants in the system. In situations like this, QRAR is a suitable alternative to QSAR since measuring MLC retention is much easier than measuring different molecular descriptors needed to build the QSAR model. Addition of 10% 2-propanol to a micellar system (hybrid system) proved to be the best chromatographic system for the best estimation of the phenols bioactivity. Other chromatographic factors such as pH and stationary phase also showed significant effect on the correlation between capacity factor k' and log 1/C. PMID- 1877752 TI - pH dependence of hydrochloric acid diffusion through gastric mucus: correlation with diffusion through a water layer using a membrane-mounted glass pH electrode. AB - Solute diffusion coefficients (D) can indicate a dependence upon actual solute concentrations. Here a single compartment has been utilized, in which effective HCl diffusion to a membrane-mounted glass pH electrode can be measured across the pH spectrum. The study has investigated HCl diffusion through both mucus and water layers as a function of HCl concentration. The observed dynamic responses of a liquid-film and mucus-coated electrodes over a range of HCl concentrations suggest that the speed at which equilibrium is attained is pH dependent; equilibrium was reached rapidly under more acidic and alkaline conditions. Estimated values of DHCl also indicate a strong pH dependence for both liquid film and mucus. In both instances, a greater than 10-fold reduction in DHCl at pH 7.5 as compared with that at pH 3.5 has been demonstrated. Furthermore, estimated values of DHCl are approximately 4-fold smaller through the mucus gel, as compared with a water layer. The findings indicate that the most powerful influence on diffusional resistance is pH itself, whereby a marked drop in H+ diffusion is likely to occur towards neutral pH irrespective of the composition of the gel barrier. Possible implications of the findings are discussed in relation to mucosal protection from acid. PMID- 1877753 TI - Simplified sample preparation for fluoride determination in biological material. AB - A simple and rapid preparation method for the determination of fluoride in biological materials (blood and food) of various origins, is described. A homogenized sample was placed in a plastic diffusion cell and calcium phosphate added, it was then dried at 55 degrees C and treated with 70% HClO4 and 40% AgClO4. After digestion for 24 h at 55 degrees C, the fluorides released were fixed on the upper part of a diffusion cell containing a thin layer of NaOH. The analyses of the diffused fluoride were carried out with an ion-selective electrode. The proposed microdiffusion method, without mineralization, enables quantitative separation of the fluoride from the biological samples. PMID- 1877754 TI - Evaluation of microwave digestion and solvent extraction for the determination of trace amounts of selenium in feeds and plant and animal tissues by electrothermal atomic absorption spectrometry. AB - A sensitive method for the accurate determination of Se in agricultural products at sub-ppm levels is described. The proposed procedure involves the wet oxidation of samples by using a mixture of nitric, sulphuric and perchloric acids, co extraction of Se and added Pd with diethylammonium N,N-diethyldithiocarbamate in chloroform, and electrothermal atomic absorption spectrometric determination of Se in the organic extract. Atomization and extraction conditions are discussed. Special attention is given to the wet oxidation step, and its advantages in speed and simplicity over conventional heating have been evaluated using an automated microwave digestion system. The results reported, obtained from several reference materials, confirm the accuracy of the method with which a detection limit of 0.002 micrograms g-1 of Se can be achieved. PMID- 1877755 TI - Duodenal glands of the pony (Equus caballus). AB - The ultrastructure and histochemistry of the duodenal glands of the pony (Equus caballus) was examined in four horses. Unlike that of most species except for the rabbit, the submucous glands of the horse contain two distinct cell types, serous and mucous. These cells are described. PMID- 1877756 TI - [The development of the bovine stomach: morphologic and morphometric analysis. II. Observations of the morphogenesis associated with the omasum and abomasum]. AB - This study represents a continuation of part 1 of a study of the development of the bovine stomach. Material and methods are more fully described in part i of the study. In this part 2 of the study further developmental stages and morphometric analysis is presented. PMID- 1877757 TI - [The development of the bovine stomach: morphologic and morphometric analysis. III. Spatial and morphometric reconstruction]. AB - This work represents a summary of the study presented in parts I and II, previously published in this journal. The data collected in those studies is presented in three dimensional reconstructions of the stomach of the developing calf. PMID- 1877758 TI - Arthrographic observations of the equine distal interphalangeal joint (Articulationes interphalangeae distalis manus) and navicular bursa (Bursa podotrochlearis). AB - Twenty cadaver limbs of adult horses were examined by arthrographic examination of the distal interphalangeal joint. The joint capsule and space is described. Comparison is made with existing descriptions. PMID- 1877759 TI - Left cranial vena cava in a horse. AB - A complete left cranial vena cava (LCVC) was found in a normal horse. The LCVC was well developed, but there was a complete absence of the right cranial vena cava. The azygous vein was normally distributed on the right side of the thoracic vertebral bodies but passed ventral to the aortic arch to empty into the cranial vena cava on the left close to the origin of the aortic arch. The LCVC passed over the dorsal aspect of the left atrium to reach the coronary sulcus on the caudal aspect of the heart. The LCVC opened into the right atrium via a 5 cm diameter orifice (orifice of coronary sinus). The vena cordis magna joined the LCVC 6 cm from the orifice of the coronary sinus. Complete dissection of the horse revealed no other developmental abnormalities. This case is compared with similar cases in the literature. PMID- 1877760 TI - [Histomorphometric study of the morphological variations of the thyroid follicles in the rat as a function of age and sex]. AB - The thyroid glands of male and female rats (Sprague Dawley) 10 to 60 weeks of age were examined histomorphometrically. The results show a clear sex dimorphism. The thyroid follicles in the male animals show a greater functional activity than in the female animals. But while the morphology of the follicles in the females was constant throughout the period of observation, in the males the activity gradually diminished. PMID- 1877761 TI - Development of the bovine duodenum with reference to enterochromaffin cells. AB - The present light microscopic study describes the morphological changes which occur in the duodenal mucosa of the bovine fetus from the third month of gestation until birth with regard to the sequence of appearance and morphology of enterochromaffin cells. The mucosa of the duodenum is prepared for digestive activity during the first months of development. This becomes obvious in the early differentiation of the fetal intestinal mucosa. The enterocytes in villus epithelium contain glycogen in the early months. These glycogen pools seem to shrink during the following months. They may provide a metabolic reserve for the fetus, which derives all of its nutrition from carbohydrates. Enterochromaffin cells appear in the three month old bovine fetus with two cell-types situated in the epithelial lining of crypts and villi. The density of enterochromaffin cells increases during gestation. There were no findings to indicate that the fetal enterochromaffin cells did not originate from endoderm. The early appearance from enterochromaffin cells (which are the producers of serotonin, 5 hydroxytryptamine) correlates with first gastrointestinal movements, which are known to commence in the first third of gestation, leading us to believe that 5 HT represents the chemical inducer of muscular motility in the developing intestine. PMID- 1877762 TI - [The deciduous hoof capsule (Capsula ungulae decidua) of the equine fetus and newborn foal]. AB - The term Eponychium is used to describe the deciduous hoof capsule in veterinary medical and embryological literature. In other aspects of veterinary medicine, the term is generally reserved for the perioplic corium of the permanent hoof. In order to clarify this double usage, the structure and origin of the hoof epidermis from 10 equine fetus at different stages of development and 4 newborn foals were investigated and described using light microscopical techniques. Epidermal tubules and lamellae are already present in the non-cornified fetal hoof epidermis. These structures, along with the formation of a white line, allow this epidermis to be divided into the same segments as are commonly used when referring to the permanent hoof. The greatest part of the deciduous hoof epidermis consists of the sole and frog, with significant portions forming in the coronary corium and that of the hoof wall as well. The perioplic corium only makes up insignificant portions of the fetal hoof capsule, however. Between the second half of the gestation period and birth, this deciduous (primary) hoof capsule is continually being replaced from below by newly-forming, cornified permanent hoof capsule. On the basis of its structure and origin, we therefore suggest that the term "deciduous hoof capsule (Capsula ungulae decidua)" be used as a replacement for the word "Eponychium" when referring to the primary hoof epidermis. PMID- 1877763 TI - [Myology of the pelvic limb of the domestic turkey Meleagris gallopavo]. AB - Pelvic limbs of 150 turkeys from a normal farmer's strain and from a Broad Breasted strain were examined by dissection to determine growth from birth to adulthood. Schematic figures and photographs show the course of the dissection. The pictures show how the muscles are related to the skeleton of the pelvic limb in the farmer's strain as well as demonstrate the surfaces upon which the muscles insert. The configuration of the muscles in the turkey are similar to the generally known model in birds. It is necessary, however, to describe the musculature and its relations to the skeleton before functional conclusions can be drawn or before studies of deficiencies in movements related to the selection of broad breasted strains can be made. PMID- 1877764 TI - Relationship of temperature pattern and serious bacterial infections in infants 4 to 8 weeks old 24 to 48 hours after antibiotic treatment. AB - STUDY OBJECTIVE: A new management approach to selected febrile infants 4 to 8 weeks old evaluated for possible sepsis is outpatient ceftriaxone therapy, with subsequent re-evaluation 24 to 48 hours after presentation. This study assessed whether the temperature profile of such infants during the 24- to 48-hour period after treatment distinguished those with from those without serious bacterial infections (SBIs). DESIGN: Prospective, descriptive clinical study. PARTICIPANTS: One hundred sixty-one febrile infants 4 to 8 weeks old. SETTING: An urban pediatric emergency department and hospital. MEASUREMENTS AND MAIN RESULTS: All infants underwent a sepsis evaluation (lumbar puncture, CBC/blood culture, and urinalysis/urine culture) and were hospitalized for at least 48 hours. Temperatures were measured on presentation and then every four hours during hospitalization. All infants received parenteral third-generation cephalosporin antibiotic therapy, and none received antipyretic medication unless fever was documented. Fever (rectal temperature of more than 38.0 C) was documented during the 24- to 48-hour period after presentation in 28 infants (17.6%)--one of a total of 18 infants (5.6%) with SBI and 27 of a total of 143 infants (19%) without SBI (alpha, more than .2: power .30). All bacterial isolates in cases of SBI were susceptible to third-generation cephalosporin antibiotics. All repeat blood and urine cultures that were performed in infants with bacteremia or urinary tract infections, respectively, were negative 24 hours after presentation. CONCLUSION: Infants 4 to 8 weeks old who remain febrile during the 24 to 48-hour period after presentation and initiation of parenteral antibiotic therapy are less likely to have SBI. This study did not have sufficient power for this difference to be statistically significant. PMID- 1877765 TI - Diazepam and intubation in emergency treatment of seizures in children. AB - STUDY OBJECTIVES: This study was undertaken to determine the incidence of endotracheal intubation after the use of diazepam compared with phenobarbital or phenytoin in emergency treatment of seizures in children. DESIGN: The records of all children (98) were reviewed in a case-control fashion. A logistic regression model was used to determine whether there was an association between diazepam administration and intubation, adjusting for all other covariates (age, weight, convulsion time before first anticonvulsant was given, response latency, diagnosis, and therapy). SETTING: All children were treated in an emergency department and then transported to a tertiary pediatric center by a pediatric transport team. TYPE OF PARTICIPANTS: All patients were children, with a median age of 2.7 years (range 0.17 to 15.3 years). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Only the use of diazepam was found to be significantly associated with intubation after adjusting for all other covariates (adjusted odds ratio, 49.4; P less than .001). In the comparison of diazepam versus phenobarbital or phenytoin used as the first anticonvulsant, median response latency did not differ (27.0 vs 32.5 minutes, P greater than .83). CONCLUSION: A significant association was found between diazepam use and intubation. Response latency was not shorter when diazepam was used as the initial anticonvulsant compared with phenobarbital or phenytoin. PMID- 1877766 TI - Pediatric emergency department complaints: a three-year analysis of sources and trends. AB - STUDY OBJECTIVE: To identify the incidence and major causes of patient and parental complaints in a pediatric emergency department. DESIGN: Retrospective analysis of complaints received regarding patients seen between January 1987 and December 1989. SETTING: ED of Children's Hospital of Pittsburgh. PARTICIPANTS: All complaints received during the three-year period. INTERVENTIONS: Complaints were reviewed for reason, validity, and location at which patient was seen. MEASUREMENTS AND RESULTS: One hundred seventy-six complaints from a total of 154,648 ED visits yielded a frequency of 1.1 complaints per 1,000 patient visits. Main reasons for dissatisfaction were misdiagnosis, billing, and inadequate treatment; 49% of complaints were judged valid. There were 0.69 complaints per 1,000 patient visits in the nonurgent medical portion of the ED. Patients seen emergently (critical care and trauma) had a significantly lower complaint frequency of 0.08 per 1,000 patient visits (P less than .001 by chi 2 analysis). CONCLUSION: Assessment of ED complaints is useful to highlight areas of patient dissatisfaction and develop plans for improving patient care. PMID- 1877767 TI - Respiratory effects of spinal immobilization in children. AB - STUDY OBJECTIVE: To assess the restrictive effects of two spinal immobilization strapping techniques on the respiratory capacity of normal, healthy children. DESIGN: Prospective study with each subject serving as his own control. PARTICIPANTS: Fifty-one healthy children 6 to 15 years old. INTERVENTIONS: Participants' forced vital capacity (FVC) measurements were first obtained with children standing and lying supine and then in full spinal immobilization using two different strapping configurations, cross straps and lateral straps. Straps were tightened to allow one hand to fit snugly between the strap and child. MEASUREMENTS AND MAIN RESULTS: Supine FVC was less than upright FVC (P less than .001). FVC in spinal immobilization ranged from 41% to 96% of supine FVC (80 +/- 9%). There was no difference in FVCs between strapping techniques (P = .83). CONCLUSION: Spinal immobilization significantly reduced respiratory capacity as measured by FVC in healthy patients 6 to 15 years old. There is no significant benefit of one strapping technique over the other. PMID- 1877768 TI - Narrow-angle glaucoma presenting as acute, painless visual impairment. AB - A 42-year-old woman presented with the acute onset of bilateral blurred vision that occurred immediately after bending over. She denied pain or any other associated symptoms. Markedly increased intraocular pressure readings were found. Treatment for acute narrow-angle glaucoma was initiated, and normal vision returned. This case represents an atypical presentation of acute narrow-angle glaucoma, a true ophthalmological emergency. The pathophysiology and treatment options of this disease process are summarized. PMID- 1877769 TI - Trauma-precipitated migrainous hemiparesis. AB - Migraine is a pleomorphic condition in which neurologic manifestations may be absent or a minor or a major feature. Similarly, head injury may range from trivial to lethal with regard to neurologic morbidity. Migraine may be precipitated by a variety of stimuli, including head trauma, significant or trivial. Presented is the case of a patient with migrainous hemiparesis precipitated by minor head injury. The clinical features and laboratory and radiological findings of trauma-precipitated migraine are reviewed. PMID- 1877770 TI - Permanently imbedded subcutaneous acupuncture needles: radiographic appearance. AB - During the evaluation of a victim of a motor vehicle accident, routine radiographs of the patient's cervical spine, chest, and pelvis revealed multiple radiopaque foreign bodies along his posterior neck, chest, abdomen, and pelvis. Repeat examination of the patient disclosed no evidence of foreign bodies. Further questioning revealed that the patient had received acupuncture therapy five years earlier in Korea. We discuss the radiographic findings of permanently imbedded subcutaneous acupuncture needles and their differential diagnosis. The medical complications of acupuncture are reviewed. PMID- 1877771 TI - Adenosine use during pregnancy. AB - Adenosine is a naturally occurring endogenous nucleoside that suppresses atrioventricular nodal conduction time, terminates supraventricular tachycardia, and restores sinus rhythm. Its use has been reported in children and adults but not in pregnant patients. This case documents the successful termination of a supraventricular tachycardia in a 39-week pregnant hypotensive patient. Emergency physicians may wish to consider adenosine use in pregnant patients needing emergency therapy or when conventional therapy fails. PMID- 1877772 TI - Stroke following oral trauma in children. AB - Stroke after oral trauma in children is a rare but catastrophic event. We describe two cases of stroke in children after each child fell with a writing instrument in the mouth. Both children had a latent period prior to the onset of neurologic symptoms. Ischemic infarction in the distribution of the middle cerebral artery was present in both cases. Both children were left with permanent hemiparesis. The case reports are reviewed and diagnosis and therapy are discussed. Emergency physicians should be aware of the risk of neurologic complications following apparently asymptomatic oral trauma. PMID- 1877773 TI - Dissections of the cervicocerebral arteries. AB - We present four cases of cerebral ischemia secondary to dissections of cervicocerebal arteries. The majority of patients presented with transient ischemic attacks and strokes, although one patient presented with headache and focal seizure. In addition to history and physical examination, the diagnostic evaluation of these patients included computed tomography scan, carotid duplex studies, angiogram, and, in some cases, magnetic resonance imaging studies. Initially, the patients were anticoagulated with heparin and then with warfarin for a period of six to eight weeks. The emergency physician must consider such dissections in younger patients with sudden neurologic deficits and no or few risk factors for cerebrovascular disease. In our experience, these are not rare syndromes; with proper workup, prompt diagnosis, and therapy, the prognosis is usually excellent. PMID- 1877774 TI - Carl Jelenko III, MD 1931-1991. PMID- 1877775 TI - Preventable sudden death in children with sickle hemoglobinopathies and fever: the need for a protocolized approach. PMID- 1877776 TI - Injury prevention: can we meet the challenge? PMID- 1877777 TI - Bias in searching ED patients. PMID- 1877778 TI - UC Irvine graded response system. PMID- 1877779 TI - Sunflower seed syndrome: a prickly proctological problem. PMID- 1877780 TI - The potential utility of a rapid CK-MB assay in evaluating emergency department patients with possible myocardial infarction. AB - STUDY OBJECTIVES: To determine the sensitivity, specificity, and predictive values of a new rapid creatine kinase-MB (R-CK-MB) assay compared with a standard CK-MB (S-CK-MB) assay and to determine its potential use in the evaluation of emergency department patients with possible myocardial infarction. DESIGN: Retrospective patient identification with subsequent testing of excess sera for CK-MB and total CK using an identity-unlinked procedure. SETTING: Large, urban, teaching hospital ED. PARTICIPANTS: All adult patients with excess sera and one of several defined presentations chosen to identify those with possible myocardial ischemia or infarction. Patients with clearly documented noncardiac etiologies of their symptoms or signs were excluded. MAIN RESULTS: The sensitivity, specificity, and positive and negative predictive values of 271 patient specimens for the R-CK-MB assay compared with the S-CK-MB assay were 100%, 96.8%, 75.0%, and 100%, respectively. The R-CK-MB assay was positive for 32 patients (11.8%). Of these, eight (25.0%) were admitted to unmonitored beds, and five (15.6%) were discharged home. All of these 13 patients had initial ECGs without evidence of ischemia or infarction. On follow-up, at least eight of the 13 had evidence of infarction. CONCLUSION: The R-CK-MB assay demonstrated high sensitivity and specificity compared with the S-CK-MB assay. When used for patients in whom a cardiac care unit admission is not considered, the rapid assay may identify some patients with unsuspected myocardial infarction and prevent inadvertent discharge or admission to unmonitored beds. PMID- 1877781 TI - Transesophageal electrocardiography using a temporary pacing balloon-tipped electrode in acute cardiac care. AB - STUDY OBJECTIVE: The study was undertaken to determine the feasibility of obtaining esophageal ECGs using resterilized 3F temporary pacing balloon-inflated electrodes in place of the more expensive pill-electrode and its associated expensive preamplifier. SETTING: Tests were conducted in the emergency department and ICU. TYPE OF PARTICIPANTS: Subjects were 12 acutely ill patients for whom standard 12-lead surface ECGs were insufficient to afford accurate, immediate arrhythmia diagnosis. INTERVENTIONS: Reasonable quality esophageal ECGs were obtained by use of the electrodes, generally with minimal patient discomfort. The test never required more than ten minutes. Of the 12 patients who participated in this preliminary study, esophageal ECGs enabled definitive diagnoses to be made in ten cases. CONCLUSION: The use of resterilized temporary pacing balloon inflated electrodes enables esophageal ECGs to be obtained in an acute care setting. PMID- 1877783 TI - The HIV-1 seroprevalence rate of injured patients admitted through California emergency departments. California HIV-1 Emergency Department Seroprevalence Study Group. AB - STUDY OBJECTIVES: To measure the HIV seroprevalence of injured emergency department patients in a number of California hospitals and to examine the relationship between ED seroprevalence and local AIDS incidence. DESIGN: Prospective blinded testing for HIV-1 antibody was performed on routinely collected blood samples. SETTING: Ten California hospitals; group 1 included three hospitals from counties of high AIDS incidence (more than 40 cases per 100,000 population), group 2 included three hospitals from counties of intermediate AIDS incidence (20 to 40 cases per 100,000 population); and group 3 included four hospitals from counties of low AIDS incidence (less than 20 cases per 100,000 population). TYPE OF PARTICIPANTS: Eligible patients were all adult trauma victims admitted to a participating hospital through the ED during a consecutive three-month period occurring between June and November 1989. MEASUREMENTS: HIV-1 antibody testing was done using enzyme immunoassay confirmed by immunofluorescence assay. Equivocal results were confirmed by Western blot. Mann-Whitney U test, chi 2 test, and multiple logistic regression were used where appropriate. RESULTS: There were 2,264 patients with adequate blood samples for serologic testing. The seroprevalence rates for hospitals in groups 1, 2, and 3 were significantly different (chi 2 = 8.44, P = .02): Group 1, 2.5% (19 of 756: 95% confidence interval [CI], 1.5% to 3.9%); group 2, 0.9% (10 of 1,078; CI, 0.5% to 1.7%); and group 3, 0.5% (two of 430; CI, 0.06% to 1.7%). CONCLUSION: This study suggests that local AIDS incidence rates do not necessarily predict the seroprevalence rates of injured patients who are admitted through local EDs. PMID- 1877782 TI - Prediction of electrolyte abnormalities in elderly emergency patients. AB - STUDY OBJECTIVES: To evaluate the operating characteristics of a previously published decision rule (Lowe's criteria) for the ordering of the stat serum electrolyte panel (SEP) and to identify features from the history and physical examination that are predictive for clinically significant electrolyte abnormalities (CSEA) in older emergency patients. DESIGN: A cross-sectional study using a physician questionnaire, record review, and telephone follow-up. SETTING: An urban, university hospital emergency department with approximately 70,000 patient visits a year. TYPE OF PARTICIPANTS: A convenience sample of patients 55 years of age or older who presented for care for any reason were identified by a research associate stationed in the ED. INTERVENTIONS: Physicians managing 1,766 patients were interviewed to determine the presence or absence of 20 dichotomous clinical variables, ten of which constitute Lowe's criteria set. All patients were followed by chart review and/or telephone interview. MEASUREMENTS AND MAIN RESULTS: The determination of clinical significance was made on record review using pre-established guidelines. The SEP was ordered on 800 of the patients on the index visit. The yield of CSEA in this group was 16%. Lowe's criteria operated with a sensitivity of 0.95 (95% confidence intervals, 0.89-0.98) and a specificity of 0.10 (95% confidence intervals, 0.07-0.12) for predicting CSEAs in this population. Logistic regression analysis showed that impaired ability to communicate, acute seizures, vomiting, and prior abnormal electrolytes were independent predictors for CSEA. CONCLUSION: Lowe's criteria showed useful sensitivity but poor specificity in this population. The criteria may be used to encourage selective test ordering by physicians when a low pretest probability for CSEA exists and as part of an algorithm for emergency nurses who order tests to expedite patient care. PMID- 1877784 TI - Emergency departments and crowding in United States teaching hospitals. AB - STUDY OBJECTIVES: To assess the extent and distribution of hospital and emergency department crowding nationally. DESIGN: The research design consisted of a mailed questionnaire disseminated in the fall of 1988 to the member institutions of the National Association of Public Hospitals (NAPH) and the Council of Teaching Hospitals (COTH). TYPE OF PARTICIPANTS: Study participants included hospital administrators and ED directors from 239 of the non-Veterans Administration, general acute care, US members of COTH and NAPH. MEASUREMENTS: Key measures of hospital and ED crowding including mean ED holding times for floor and ICU beds. MAIN RESULTS: Three fourths of responding hospitals reported increases in ED visits over the preceding three years. Mean ED holding times for admitted patients were 3.5 hours (median, 2.0 hours) for a floor bed and 2.9 hours (median, 1.5 hours) for an ICU bed. Half of all hospitals noted maximum waits for floor and ICU beds of ten hours or more and seven hours or more, respectively. Measures taken by hospitals to manage crowding during August 1988 included restricting access to some types of patients (mean, 3.6 days), actively transferring patients to other hospitals (mean, 2.2 days), transfer refusal (mean, 2.8 days), and total ambulance diversion (mean, 1.6 days). CONCLUSIONS: Our study strongly suggests that ED crowding is not an isolated phenomenon; ED crowding and its attendant problems appear to affect hospitals with similar adverse effects regardless of ownership. Although our results suggest that ED crowding is concentrated in metropolitan areas and in a smaller subset of hospitals, we found instances of crowding among hospitals nationwide. PMID- 1877785 TI - Medical problem solving and uncertainty in the emergency department. AB - STUDY OBJECTIVE: To compare the diagnostic processes of experienced emergency physicians with those of novices. DESIGN: Prospective, convenience sample of patients. SETTING: Emergency department of a county university medical center in a large southwestern urban community. PARTICIPANTS: Experienced emergency physicians (attending and senior residents) and novice clinicians (junior residents and senior medical students). INTERVENTIONS: Participants developed initial diagnostic impressions after reviewing the chief complaint, nurse triage notes, and vital signs. Tests were then selected, and a final diagnostic impression was identified after results were known. Clinicians also marked a visual analog scale corresponding to their estimate that each diagnostic possibility was correct. RESULTS: Experienced physicians increased their certainty more than novices (P = .014). They deviated from a standard history physical-laboratory sequence more often than novices (P = .008). CONCLUSION: Expertise in medical decision making is characterized by a moderate initial level of certainty concerning a diagnosis that significantly increases as the experienced clinician follows a flexible strategy of testing to arrive at a final diagnosis. PMID- 1877787 TI - Computers free nurses for care. PMID- 1877786 TI - Work-related stress and depression among physicians pursuing postgraduate training in emergency medicine: an international study. AB - STUDY OBJECTIVE: To compare the levels of work-related stress and depression reported by physicians-in-training in emergency medicine in three survey sites and to determine the effects of gender and marital status on stress and depression among these physicians. DESIGN: Cross-sectional mail surveys. SETTING AND TYPE OF PARTICIPANTS: Physicians-in-training in the United States, United Kingdom, and Australasia. INTERVENTION: Questionnaires requesting demographic information and including scales assessing work-related stress and depression were administered. MEASUREMENTS AND RESULTS: A 3 x 2 x 2 multivariate analysis of variance in which survey site, gender, and marital status were independent variables and stress and depression scale scores were dependent variables revealed significant differences when stress and depression were analyzed simultaneously. Univariate analyses of variance revealed significant differences in stress by survey site and gender and in depression for all three independent variables. Comparison of adjusted means revealed that respondents from the United Kingdom reported significantly higher levels of stress than did respondents from the United States and that women reported significantly higher levels than men. Respondents from the United States reported significantly higher levels of depression than did respondents from the other countries, women reported higher levels than men, and unmarried respondents reported higher levels than married respondents. CONCLUSION: Despite limitations resulting from self-report bias, cross-sectional survey methodology, sampling error, and differences in training among the three survey sites, the respondents experienced similar levels of stress and depression attributable to anticipated sources. PMID- 1877788 TI - ANA voices opposition to 'gag rule'. PMID- 1877789 TI - Bank gathers malpractice data. PMID- 1877790 TI - Caring is the key to critical care. PMID- 1877791 TI - Law restores bargaining rights. PMID- 1877793 TI - Technology improves patient care. PMID- 1877792 TI - The political nurse. PMID- 1877794 TI - Mandatory HIV testing opposed. PMID- 1877795 TI - Inadequate staffing threatens care, RNs say. PMID- 1877797 TI - Some systems change, some don't. PMID- 1877796 TI - You've decided to change jobs--now what? PMID- 1877798 TI - Computers--practical application of a vision. PMID- 1877799 TI - Crowding threatens emergency care. As I see it. PMID- 1877800 TI - Stint in Saudi Arabia was challenging. PMID- 1877801 TI - [Practical indications for anorectal manometry]. AB - Anorectal manometry has taken on an important role in the investigation of functional anorectal disorders. This investigation studies the two factors, the resistive system and the capacitive system, involved in anorectal function, continence and defecation. Practical indications can be grouped into three categories concerning different aspects of physiopathological, diagnostic and therapeutic interest. Manometry is essential in the investigation of disorders of pelvic static function, is useful in colorectal surgery and of interest in a wide range of proctological diseases. PMID- 1877802 TI - [Defecography or dynamic rectography]. PMID- 1877803 TI - [Practical indications for biofeedback type rehabilitation]. PMID- 1877804 TI - [Carcinomas of the anal canal. Chemotherapy]. PMID- 1877805 TI - [Gastro-esophageal symptoms in cirrhosis]. PMID- 1877807 TI - The dynamics of linear growth in distance, velocity and acceleration. AB - Growth of body, leg, trunk and arm length from birth to adulthood is studied in the subjects of the First Zurich Longitudinal Growth Study, using a recently developed technique, the 'structural average curve'. In this way truly longitudinal average curves are obtained for velocity, acceleration and distances, and various phases of growth are analysed not only graphically, but also by descriptive parameters in terms of timing, intensity and duration. These phases consist of the pubertal spurt (PS), the mid-growth spurt (MS) and growth in infancy. The overall pattern is the same in all variables studied: velocity drops sharply after birth, followed by a kink between 7 and 12 months, and a more gradual decrease until the MS, which peaks around 7 years. In girls the PS immediately follows the MS, while in boys a 'latency period' of approximately constant growth velocity precedes the PS, which occurs almost 2 years later, and is more intense than in girls. There are no appreciable sex differences in the MS, but the PS is later and more intense for boys, even when accounting for the smaller adult size of girls. When comparing linear variables the PS turns out to be earlier for the legs than for the trunk, whereas the trunk has an earlier MS. The trunk starts high in relative distance and in velocity after birth, whereas the legs have a high velocity throughout childhood. In adolescence the trunk again shows more intense growth. Surprisingly, the growth of the arms in many ways resembles more that of the trunk and not that of the legs. PMID- 1877806 TI - [Primary malignant melanoma of the rectum. A case report]. AB - The authors report a case of primary malignant melanoma of the rectum seen in an 84-year-old woman. This blackish tumour measuring 3 cm in diameter and situated 8 cm from the anal margin was treated by surgical excision. The patient died during the immediate postoperative period. PMID- 1877808 TI - Menarcheal age for Norwegian women born 1830-1960. AB - Data from birth records from the maternity hospitals in the three main cities in Norway have been used to study the trend in menarcheal age for women born from about 1830 to about 1960. The investigation is based on a sample of 200-300 records around every 10th year from each of the three clinics in partly overlapping time periods relating to a total of 9152 women. The recollected age at menarche fell from just above 16 years for women born around 1830 to just above 13 years for those born around 1960, the decrease being not totally linear. These results correspond closely with a previously published investigation from Oslo from about the same period of time (Brudevoll, Liestol and Walloe, 1979), but our results, which cover more of Norway, show a more linearily shaped curve than the results covering only Oslo. We have also analysed the relationships of several independent variables to menarcheal age, using multivariate linear regression methods. Besides the woman's year of birth, which was the most important variable throughout the whole period of time, various geographical variables were found to be of moderate importance. Being born in the countryside and in towns other than Oslo and Bergen led to a slightly higher age at menarche. No significant difference between Oslo, Bergen and Trondheim was detected except for the period up to about 1880 where the Bergen women had about 2.6 months earlier menarche than the Oslo women. Married women amongst the sample had experienced menarche a little earlier than the unmarried, and among married women there was an association between occupation and menarcheal age, women from the lowest social classes having the latest ages at menarche. The importance of these socially related parameters declined with time, and for women born after 1945 the difference seemed to have disappeared. The age at menarche was found to be positively related to a woman's age at first birth; the further back in time the stronger the relation. In addition, delayed age at menarche was also found to be associated with irregularities in the menstrual cycles in later life. PMID- 1877809 TI - Characterization of digital dermatoglyphic features in Salazar Valley: comparison with other Basque valleys. AB - Digital dermatoglyphics of a sample from the Basque Valley of Salazar, situated in the West of the Pyrenees, were analysed. The results showed bimanual differences in both sexes, and also sexual differences for both hands. The comparative study with other Basque valleys showed that, in spite of their supposed common origin, the geographic barriers and the isolation have generated a genetic/dermatoglyphic and linguistic differentiation. PMID- 1877810 TI - Ethnic and environmental factors affecting fetal growth in Papua New Guinea. AB - We studied 738 live singleton births in Papua New Guinea to examine the contribution of ethnic origin and environmental factors to birth weight and gestation. Maternal history, examination and post-partum anthropometry, infant anthropometry and clinical gestational assessment were performed, and placental blood slides and histology were examined. Mothers from Highlands provinces who delivered on the coast had larger babies (mean birthweight 3.34 SD 0.48 kg) than either indigenous coastal mothers (mean 3.10 SD 0.51 kg) or those migrating to Port Moresby from other coastal regions (mean 3.14 SD 0.51 kg). This was due to a combination of longer gestation and better intrauterine growth (assessed by birthweight standard deviation scores). Gestation was slightly longer in Highlands mothers delivering on the coast compared with those delivering in the Highlands, but birthweight standard deviation scores were unchanged. Malarial infection of the placenta was almost never found. Stepwise regression analysis showed that parity, maternal height, Highlands origin and maternal body mass index (weight/height2) were all significant predictors of birthweight standard deviation score, while maternal body mass index and Highlands origin were predictors of gestational length. We conclude that Highland mothers have a tendency to deliver heavier babies, and do not demonstrate the fetal growth retarding effects of altitude seen in other races. Although the incidence of low birthweight was only 7.1% in our study, we found that indices of maternal nutrition were predictors of birth weight. PMID- 1877811 TI - Basal metabolic rate and physique of Gurkha and British soldiers stationed in Britain. AB - Measurements of basal metabolic rate (BMR) and physique were made on Gurkha soldiers stationed in Britain, and on British controls matched by body weight and occupational background. Gurkhas were significantly shorter, with greater body mass index, calf circumference and subscapular skinfold thickness than the European controls, although there was no difference in BMR between the two groups. For the Gurkhas, linear regression analysis incorporating factors which may influence BMR showed a positive relationship between the length of time since leaving Nepal and BMR, supporting the view that Asians living in temperate regions have higher BMR than those living in the tropics. PMID- 1877812 TI - Family resemblance in body circumferences and their ratios: the Nancy family study. AB - The purpose of this study was to investigate the familial resemblance for individual body circumferences (suprailiac, waist, thigh and arm) and for the waist/suprailiac (as surrogate for the waist/hip) and the waist/thigh circumference ratios, in a sample of 216 unselected nuclear families with children aged 10-25 years. Familial correlations were jointly computed, using the maximum-likelihood method. The highest familial resemblance was observed for the waist circumference and for the waist/suprailiac and the waist/thigh circumference ratios. There was no significant difference between father offspring and mother-offspring correlations when considering individual body circumferences. In contrast, when considering the two ratios there was a stronger mother-child than father-child similarity. Furthermore, there was a higher resemblance of the mother with her daughter than with her son, but no significant sib sex difference in the father-offspring relationship. There was also a heterogeneity of sibling correlations for the two ratios, the like-sex pairs exhibiting higher correlations than the unlike-sex pairs. Lastly, the similarity observed between spouses, of similar magnitude to the father-offspring correlation, suggests the contribution of environmental rather than genetic factors for explaining the familial resemblance of the two ratios. In conclusion, the great family resemblance for the waist/suprailiac and the waist/thigh circumference ratios (correlations ranging from 0.23 to 0.68) appears remarkable, and should be taken in consideration, given the predictive value of these indices for disease in adulthood. PMID- 1877813 TI - [A comparative study of intra-arterial infusion chemotherapy and systemic chemotherapy in the treatment of locally advanced breast cancer]. AB - A comparative randomized study of intra-arterial infusion chemotherapy (IA) and systemic chemotherapy (IV) was carried out on 41 patients with locally advanced breast cancer, and the following results were obtained. 1) The response rate of primary lesions to IA (63.2%) was better than that of IV (40.9%). 2) In the patients treated with IA, grade of leukopenia, as well as the percentage of gastro-intestinal disorders, was low. 3) More prolonged follow-up studies are required on the therapeutic effects on micrometastasis. The author confirmed that IA was an efficacious neoadjuvant therapy in terms of down staging of locally advanced breast cancer. PMID- 1877814 TI - [Clinical study of drug accumulation in gastric cancer after preoperative intra arterial EAP II injection therapy]. AB - Preoperative intra-arterial injection therapy using etoposide, epirubicin and carboplatin (EAP II) was done for patients with resectable advanced gastric cancer. Twenty-six patients (14 males and 12 females) were treated. The concentrations of adriamycin (ADM) and platinum (Pt) were measured in cancer tissue, normal mucosa and regional lymph-nodes which were obtained operatively and in sera just before operation. But the concentration of etoposide was not measured, because when we used preoperative intra-arterial injection therapy using etoposide, epirubicin and cisplatin (EAP I), the mean concentration of etoposide was less than the detectable limit in all tissues and in sera. There were no significant differences among the mean concentrations of ADM in all tissues and in sera. And the mean concentration of ADM in cancer tissue was not higher than that of intra-arterial EAP I injection therapy. The mean concentration of platinum in sera was significantly lower than in cancer tissues, normal mucosa and lymph-nodes. And the mean concentrations of platinum in cancer tissues and lymph-nodes were higher than those of intra-arterial CDDP or EAP I injection therapy. It was concluded that preoperative intra-arterial EAP II injection therapy may be an effective method to improve the usefulness of preoperative intra-arterial injection therapy for gastric cancer. PMID- 1877815 TI - [Evaluation of effective neo-adjuvant chemotherapy (FLEP therapy) in the treatment of advanced gastric cancer]. AB - Ten patients with non-resectable gastric cancer were subjected to a neo-adjuvant chemotherapy (FLEP therapy), consisting of 4 drugs (leucovorin and 5-FU i.v., CDDP and etoposide i.a.) combination therapy from August 1989 to April 1991. The response rate of this therapy with primary lesions, metastatic lymph-nodes (mainly paraaortic lymph nodes), metastatic liver tumor and peritoneal dissemination were 50, 50, 25 and 33%, respectively. Five cases underwent total gastrectomy. Pathological evaluation of these cases was Grade 1 or 2. Side effects were mainly gastrointestinal disturbances, namely stomatitis, nausea, vomiting and anorexia, along with bone marrow suppression. Performance status of these patients improved to a significant degree by the therapy. This therapy seemed to be effective in controlling paraaortic lymph-node metastasis. The advantage of i.a. delivery was investigated by Tc-MAA scintigraphy. The distribution of Tc-MAA after i.a. injection suggested that i.a. chemotherapy enhanced intraabdominal drug concentration. There is no established treatment for far advanced cases, so this therapy seems to be worth a try. PMID- 1877817 TI - [Effects of preoperative local administration of BRM on cellular immunity and prognosis of patients with esophageal cancer]. AB - We studied the effects of OK-432 administered preoperatively on the cellular immunity and prognosis of patients with esophageal cancer. The preoperative injection of OK-432 was effective to preserve the NK activity in the peripheral blood. Especially the local priming and eliciting with OK-432 seemed to contribute to the activation of NK cells in the regional lymph nodes and to the improved prognosis of the patients. PMID- 1877816 TI - [Hyper-thermo chemotherapy of esophageal cancer with thermosensitive liposome, TAC-1043]. AB - Antitumor activity of the thermosensitive liposome, TAC-1043, was examined. The TAC-1043, produced by Takeda Chemical Industries, Ltd., contained entrapped cisplatin in a large unilamellar vesicle (LUV). LUV is composed of dipalmitoylphosphatidyl choline (DPPC) and distearoylphosphatidyl choline (DSPC) in the ratio of 9:1. The in vitro sensitivity of TAC-1043 was examined by SDI assay with MTT, using human esophageal cancer cell lines (TE-2, KY). TAC-1043 was effective at the concentration of 10 micrograms/ml, 41 degrees C and 43 degrees C. The in vivo effect of TAC-1043 together with hyperthermia was examined using mouse tumor MM 48. TAC-1043 combined with hyperthermia significantly suppressed the tumor proliferation. PMID- 1877818 TI - [Pharmacokinetics following intraperitoneal infusion of cisplatinum with and without sodium thiosulfate rescue in carcinomatous peritonitis in advanced gastric cancers]. AB - The pharmacokinetics of ip cisplatinum (100 mg/body) was studied in 10 patients with advanced gastric cancer. Five patients were administered ip-cisplatinum with STS and another 5 patients were given the same without STS. As a result, 1) the level of free-CDDP in ascites fluid was significantly elevated after administration, showing that free-CDDP possessing anti-tumor activity persisted in the ascites fluid for a long time and reached the peak concentration 30 minutes after administration. 2) The free-CDDP transferred into the blood after administration also persisted for a long time in parallel with changes in the free-CDDP level in the ascites fluid. 3) The AUC, MRT and VRT of the free-CDDP concentration in the peritoneal cavity after ip administration of CDDP were high, clearly indicating the direct effect on peritoneal concentration. 4) The AUC, MRT and VRT of free-CDDP in the venous phase after ip administration of CDDP were higher than after its iv administration, suggesting that effects equivalent to or greater than those of the iv route drug can be expected in the venous phase. 5) The frequency of side effects induced by the combination of STS was lower than that of side effects induced by the administration without combined STS. Much larger doses of CDDP may be given ip by combining with STS. PMID- 1877819 TI - [Evaluation of carboplatin administration into the serous cavity in the treatment of malignant effusion]. AB - Carboplatin, a new analogue of cisplatin, was administered into the serous cavity in nine primary lung cancer patients with malignant effusion, consisting of six malignant pleural effusions, two malignant pericardial effusions and one malignant ascites. Clinical effects, toxicities and pharmacokinetics were studied. The doses of carboplatin were 300 mg/m2 in seven patients, 200 mg/m2 in one patient and 1,100 mg/body in one patient. In seven evaluable patients, consisting of four non-small cell lung cancers and three small cell lung cancers, the response rate was 85.7% with 3 CR cases, 3 PR cases and 1 NR case. As toxicities, thrombocytopenia was observed in 57.1%, leukopenia in 57.1%, anemia in 71.4%, anorexia in 42.9%, nausea or vomiting in 28.6%, and low grade fever in 14.3%. However local pain, renal or liver dysfunction were not observed. The pharmacokinetics of free platinum concentration was analyzed with a two compartment model (t1/2 beta = 18.60 hours) and 14.8% of total platinum remained free in effusion 24 hours after intracavitary administration. A high level of free platinum in effusion was maintained over a long period after carboplatin administration. This method was considered to be effective for the treatment of malignant effusion from the viewpoint of pharmacokinetics and less toxicity. PMID- 1877820 TI - [Chemotherapy in malignant gynecologic tumors using intraperitoneal catheter with a subcutaneous reservoir]. AB - Malignant gynecologic tumors are liable to encourage intraperitoneal dissemination and liver metastasis. Using an implantable reservoir (R), we undertook intraperitoneal (ip) administration of CDDP (P) and etoposide (E). After the ip injection of 150 mg of P, 300 mg of E was diluted with 1,500 ml of saline solution through the R. P and E of the intraperitoneal fluid and blood were measured after the administration, and the therapeutic results were evaluated. The blood concentration of P and E reached peaks at 30-60 minutes and at about 4 hours, respectively, after administration. Detectable levels of both P and E were observed at up to 48 hours after administration. In the first treatment of patients who showed severe peritonitis carcinomatosa and high intraperitoneal levels of proteins, the transfer to blood of P from the peritoneal cavity was slow, but as the treatment progressed (second and third administrations) protein binding P decreased and peritoneal permeability improved. Both maximum blood P concentrations and the concentrations of free P were also increased 48 hours after administrations. The area under the curves (AUC) of the blood free P and E concentrations were 8.0 and 274.0 (microgram/ml x h), respectively, which were higher than those following intravenous administration. The results showed 3 CR and 6 PR. This ip regimen obtained a 64.3% response rate for measurable lesions. A patient in stage IV of ovarian cancer showed marked remission of a liver metastatic focus. Repeated ip administration through R proved to be effective by means of systemic therapy. PMID- 1877821 TI - [Intraperitoneal cancer chemotherapy using an implantable reservoir in patients with peritonitis carcinomatosa]. AB - Intraperitoneal cancer chemotherapy using an implantable reservoir has been recognized as an effective treatment. In this report, we evaluate treatment results in 20 cases undergoing this chemotherapy and the correlation between reservoir-use period and cumulative survival rates. Twenty patients with an average age of 59.3 years were all observed to have peritoneal dissemination during operations in the period of January 1987 through January 1991. Their primary diseases were 10 cases of gastric cancer, 8 cases of colorectal cancer, 1 case of appendiceal carcinoma, and 1 case of malignant tumor of retroperitoneum. Intraperitoneal reservoirs were implanted in surgically-made pockets in subcutaneous lower abdomen, and their catheters were inserted into Douglas cul de sac. Medications used were CDDP, MMC, and 5-FU. The average number of administration was about 6 or 7, but, the maximum number was 67 in one case. Contrast media or RI infused via reservoirs was recognized to diffuse widely within the peritoneal cavity. Eighteen of 20 cases (90%) obtained good conditions to undergo ambulant treatments. The longest survival records were 827 days in a gastric cancer group, 639 days in a colorectal cancer group, and 326 days in a malignant tumor of retroperitoneum group. Two cases having the former two survival records are still alive at this writing. One case with appendiceal carcinoma is PS 0 and now under out-patient treatment at 2 years and 6 months after operation. The 50% survival period, and 6-month, 1-year, and 2-year cumulative survival rates were 8.8 months, 60%, 40.5%, and 37%, respectively in the gastric cancer group; and 13.5 months, 75%, 63%, and 31.5%, respectively, in the colorectal cancer group. On the contrary, 50% using period, and 6-month, 1 year, and 2-year cumulative using rates were 5.3 months, 40%, 10%, and 10%, respectively, in the gastric cancer group; and 7.9 months, 58%, 0%, and 0%, respectively, in the colorectal cancer group. Evaluation of the correlation between the reservoir use periods and cumulative survival rates has led to the conclusion that cumulative survival rates are extended significantly p = 0.0011 in each cancer group with more than 6 months treatment period compared to within each cancer group with less than 6 months treatment. 1) Intraperitoneal cancer chemotherapy using an implantable reservoir enables patients to receive treatment at outpatient clinics. 2) The continuous treatment for more than 6 months suggests the possibility for longer survival. PMID- 1877822 TI - [Antitumor Effector mechanism of plant alkaloid preparation, cepharanthin, by intratumoral administration]. AB - The antitumor effect of biscoclaurine alkaloids, at a distant site was examined in the double grafted tumor system, in which mice received simultaneous intradermal inoculations of Meth-A in both right (10(6) cells) and left (2 x 10(5) cells) flanks and were then injected with 0.5 mg of CR in the right tumor on days 3, 4 and 5. CR inhibited the growth of not only the right but also the left, non-treated tumor. In order to examine the role of lymph nodes in the antitumor activity of CR, regional (axillary and inguinal) lymph nodes were resected. Since in resected mice the antitumor activity of CR against the left tumor was weakened, the regional lymph nodes have a very important role in the antitumor effect of intratumoral administration of CR at a distant site. Spleen cells prepared from CR treated mice were examined for Lyt-1, Lyt-2 and L3T4 phenotypes. The number of Lyt-1 positive lymphocytes increased in the spleen after intratumoral administration of CR. Isolated tumor cells obtained from the right tumor treated with CR and the left side tumor on day 6 were cultured for 24 h. The culture supernatants were harvested and tested for the presence of chemotactic activity for neutrophil or macrophage. Significant neutrophil chemotactic factor (NCF) activity was detected in the culture media from CR treated right tumor tissue, and macrophage chemotactic factor (MCF) activity was detected in the culture media from left tumor tissue. CR-induced NCF was partially neutralized by treatment with anti-human IL-8 IgG, and might be murine IL-8 factor. These results suggest that intratumoral administration of CR first induces neutrophils in the right tumor, then Lyt-1 positive cells in the spleen, and subsequently induces cytotoxic macrophages in the left, non-treated tumor, thus bringing about the regression of distant tumors. PMID- 1877823 TI - [A loco-regional cancer chemotherapy, using a fibrin clot as a drug carrier--the oncolytic effects and putative mechanisms]. AB - Anticancer drug (AD), adriamycin (ADM) or cisplatinum (CDDP) were individually encapsulated into an insoluble fibrin clot (FC), using our own technique. FC-ADM or FC-CDDP was intraabdominally placed in AH 130-bearing rats, and ADM or CDDP solution was intraabdominally injected (IP) into other cancer-bearing rats. The survival time was recorded and related oncolytic mechanisms were investigated. Eleven of 14 rats treated with FC-CDDP, and four of eight rats given FC-ADM, survived for more than 200 days. In these animals, the ascites disappeared within 10 to 14 days after the treatment, and there was neither a recurrence of ascites nor metastases. Eight of these rats underwent challenge of AH 130 cells. All the challenged animals revealed no evidence of recurrence of the cancer and showed a killing activity against the AH 130 cancer cells. Survival time in the other cancer-bearing rats was shorter than three weeks, and the direct cause of death was cachexia. Our newly devised FC-AD showed high activity against implanted AH 130 tumors. These activities are attributed to both a sustained release of AD and immunoresponses induced with FC-AD. PMID- 1877824 TI - [Endoscopic injection of liposomal adriamycin targeting lymph node metastasis of gastric cancer]. AB - Gastric submucosal injection of 5 mg liposomal adriamycin (L-ADM) close to the main gastric cancer tumor was done in 15 patients by endoscopy. This approach was based on the idea that preoperative adjuvant chemotherapy targeting lymph node metastasis in patients with gastric cancer may be effective for prevention of lymph node recurrence. ADM concentrations in the regional lymph nodes were assessed and compared with those in patients who were administered 5 mg of free adriamycin (F-ADM) i.v. preoperatively. ADM concentrations in Group 7 lymph nodes (according to the General Rules for Gastric Cancer Study) were: After 2 days; 7.21 +/- 5.98 micrograms/g (n = 2) in the L-ADM group and 0.59 +/- 0.23 micrograms/g (n = 3) in the F-ADM group. After 4 days; 4.93 +/- 3.93 micrograms/g (n = 2) in the L-ADM group and 0.36 +/- 0.0 micrograms/g (n = 2) in the F-ADM group. After 6 days; 2.08 +/- 0.49 micrograms/g (n = 2) in the L-ADM group and 0.05 +/- 0.05 micrograms/g (n = 3) in the F-ADM group. L-ADM group: those who had L-ADM injected into the side of the lesser curvature of the stomach. F-ADM group: those who had F-ADM administered i.v. These data demonstrate that gastric submucosal injection of L-ADM is well suited for specific delivery to the regional lymph nodes, suggesting that this type of administration may prevent lymph node recurrence of gastric cancer by targeting lymph node metastasis. PMID- 1877825 TI - [Enhanced effect of intraperitoneal administration of CDDP combined with caffeine against peritoneal metastasis]. AB - The enhanced effect of CDDP combined with caffeine against P-388 leukemia was investigated. No synergistic effect was shown after one hour simultaneous treatment with CDDP and caffeine. But the growth inhibition was enhanced by the addition of caffeine after one hour treatment with CDDP. It is suggested that caffeine inhibits DNA repair by the reduction of CDDP-induced elongation of G2 + M phase. The increase in life span of mice after ip transplantation was observed by frequent ip injections of caffeine after CDDP injection. It is suggested that the effect of intraperitoneal administration of CDDP against peritoneal metastasis is enhanced by combination with caffeine. PMID- 1877826 TI - [Development of slow releasing anticancer drug based with absorbable biomaterial chitin]. AB - To have a comparatively more slowly releasing anticancer drug with effectiveness, Plachitin was prepared by chemical combination of CDDP and chitin (poly-N-acetyl D-glucosamine). Chitin is absorbed by the living body over several months. To investigate the slow releasing property, it was implanted in thigh muscle of mice and rabbit. Pt level in different organs and in urine was measured at regular intervals. Pt level in implanted muscles was higher in comparison to low serum level in mice. It was released slowly over 1 to 2 months in mice, whereas in rabbit it took about three weeks. Pt releasing period of the Plachitin was different according to the adopted method of implantation. Anticancer effect of Plachitin was investigated by injecting 180 sarcoma cells in mouse peritoneal cavity and subsequent implantation of Plachitin. In control groups chitin was used instead of Plachitin. The survival rate of mice in the Plachitin group after 14 days was higher than in the chitin group, and the anticancer effect of the Plachitin was confirmed. PMID- 1877827 TI - [Loco-regional cancer therapy for hepatic metastasis]. AB - We undertook a clinical evaluation of chemotherapy for hepatic metastasis of gastric, colorectal and breast cancer. Between 1980 and 1989, chemotherapy for hepatic metastasis of gastric cancer was performed in 96 cases. Between 1973 and 1989, chemotherapy for hepatic metastasis of colorectal cancer and breast cancer was performed in 40 and 14 cases. RESULTS: (1) In hepatic metastasis of gastric cancer, the 50% survival period was 149 days in local injection therapy, 132 days in arterial infusion therapy and 117 days with no chemotherapy. There was no significant difference in the survival period in gastric cancer. (2) In hepatic metastasis of colorectal cancer, the 50% survival period was 445 days in arterial infusion therapy, 206 days in local injection therapy and 96 days with no chemotherapy. The survival period with hepatic metastasis of colorectal cancer that had undergone chemotherapy was longer than for no chemotherapy. (3) In hepatic metastasis of breast cancer, arterial infusion therapy was more effective, and the survival period was prolonged significantly. PMID- 1877828 TI - [Trans-arterial infusion chemotherapy through the inferior epigastric artery for malignant abdominal tumors without laparotomy]. AB - A new technique of intra-arterial catheterization through the inferior epigastric artery using a subcutaneously-implanted silicon reservoir was tried for arterial infusion chemotherapy in patients with cancer located in specific lesions. Eight surgically uncontrollable tumors, consisting of 6 hepatic metastasis, one surgically incurable gastric cancer and one recurrent rectal cancer, were treated by continuous arterial infusion of cis-diamminedichloroplatinum (CDDP) using this new method. Clinical antitumor effect was evaluated by CT scan, sonography or operation. CR, PR and NC were observed in 3, 3 and 2 patients, respectively. No significant difference in CDDP levels in serum was found between CR plus PR and NC cases. Since this method can be done without laparotomy, more patients may benefits from arterial infusion chemotherapy. PMID- 1877829 TI - [Five-hour hepatic arterial infusion of high-dose 5-FU on weekly schedule for liver metastases from colorectal cancer]. AB - The study of 5-hour hepatic arterial infusion of high-dose 5-FU on a weekly schedule (weekly high-dose 5-FU HAI: WHF) was conducted to reveal a new pump-free regimen to avoid the reduction of QOL due to continuous infusion pumps. By the phase I study, the recommended dose was determined to be 1.000 mg/m2/5 hrs qw. Thus far, 20 cases entered the phase II study of this regimen, and 1 CR and 10 PRs were observed in 15 evaluated cases without major toxicity. This regimen is highly effective for liver metastases from colorectal cancer without reduction of QOL in patients by pumps. A study of this regimen involving a large number of cases is required. PMID- 1877831 TI - [An experimental study on portal infusion of 5-fluorouracil]. AB - We conducted these experiments to investigate the differences between continuous portal and one shot portal infusion of 5-fluorouracil (5-FU) using male Donryu rats. Continuous portal infusion of 5-FU (20 mg/kg/day x 5 days) revealed no remarkable side effects on the rats with significant decrease in the number of liver metastases generated by intraportal inoculation of ascites hepatoma AH60C. Consecutive 5-day administration of 5-FU (20 mg/kg x 5) by one shot method via spleen resulted in no metastases but caused death in 75% of rats because of severe leukopenia and dehydration. The rats receiving one shot infusion of 5-FU (33.3 mg/kg x 3, day 1, 3, 5) via spleen showed a significant decrease in the number of metastases without lethal side effects. Continuous portal infusion of 5 FU would be a safe and effective therapy to prevent liver metastases, whereas one shot portal infusion of 5-FU may give rise to severe side effects while preventing liver metastases. PMID- 1877830 TI - [Clinical application of chemotherapy via the portal vein with liposome encapsulated adriamycin in inoperable metastatic liver cancer]. AB - We studied the effects of liposome-entrapped adriamycin (L-ADM) administered via the portal vein and the clinical application of this treatment in the therapy and inhibition of liver metastasis, experimentally and clinically. Liposomes composed of egg phosphatidylcholine (cholesterol 50 mol%) were used as drug carriers. We examined the distribution in tissues and antitumor effect of freeze-dried L-ADM administered via the portal vein to rabbits bearing VX2 tumors. The liver concentration of ADM increased after delivery and cardiac uptake decreased compared with free drug treatment. The life span was prolonged by L-ADM treatment compared with the control group and the free ADM group. This L-ADM administration was confirmed to be safe and revealed a decrease in the heart toxicities compared with free adriamycin. Nineteen cases were studied from Jan. 1986 to May 1991 via the portal vein and the clinical effects were evaluated. From Mar. 1988 to date, 10 cases were treated with L-ADM (20-30 mg every 2 weeks/body) in patients with inoperable cases using subcutaneously implanted reservoir. The median survival was 450 days; 275 days for colon cancer, 492 days for gastric cancer, and 1,052 days for uterine cancer (range: 136-1,152 days), compared with 141 days (range: 52-253 days) in 9 cases of historical control treated with free-ADM via the portal vein. These results suggest that chemotherapy via the portal vein with L ADM for metastatic liver cancer may increase survival time. PMID- 1877832 TI - [Experimental studies on prevention of liver metastases by continuous intraportal chemotherapy]. AB - Our experiment was designed to elucidate the efficacy of continuous intraportal chemotherapy (CIPC) for the prevention of liver metastases. Catheter was introduced into ileocecal vein of white rabbit for administration of adriamycin (ADM). VX2 cells were inoculated into portal vein to form liver metastases. Three experiments were designed as follows: 1) Immediately after inoculation of tumor cells, ADM was administered continuously for 7 days. 2) Continuous administration of ADM started on the 3rd day after inoculation of tumor cells. 3) Immediately after inoculation of tumor cells, ADM was administered by CIPC or systemically for 7 days. The same number of tumor cells were inoculated into portal vein and no treatment was given in control group. The rabbits were sacrificed on the 14th day. Number and size of liver metastases were calculated. Results were as follows: In 1) and 2), the metastases in CIPC group were significantly decreased in number and size compared with those in control group. In 3), no metastasis was observed in CIPC group, but a third of the rabbits developed metastases in systemic group. These results suggest that CIPC is effective for prevention of liver metastases and its efficacy is greater than for systemic chemotherapy. PMID- 1877833 TI - [Comparative study on the comparative efficacy of hepatic arterial or portal venous infusion of adriamycin to control hepatic carcinoma growth]. AB - To compare the efficacy of intrahepatic arterial and intraportal venous infusions of anticancer drugs, the following two experiments were performed. 1. Adriamycin (3 mg kg) aqueous solution (ADR) was administered into hepatic artery (HA group) and portal vein (PV group) of a rabbit with 2 cm diameter VX2 liver tumor. The ADR levels of the tumor tended to be about 3-fold higher in HA than in PV group (p less than 0.1) one hour after ADR infusion. No significant difference was seen in the ADR levels of liver, heart, kidney, and bone marrow between the two groups. The ADR concentration ratio of tumor to liver was significantly higher in HA group than in PV group. 2. VX2 tumor cells (1 x 10(7) cells) were transplanted through the portal vein of the rabbit. ADR aqueous solution (1 mg/kg, 5 ml) was infused into the rabbit liver via HA and PV, at 3, 5, and 7 days after tumor inoculation. The rabbits were killed and the livers were excised 21 days after tumor implantation. The number of VX2 tumor nodules on the liver surface was less in HA group than in PV group. These results suggest that hepatic arterial infusion of anticancer drug is more useful to inhibit the growth of liver tumor than portal venous infusion. PMID- 1877834 TI - [An experimental study of ethanol injection on VX2 liver cancer]. AB - Ethanol injection therapy for rabbit VX2 cancer of the liver was performed to measure the extent of ethanol infiltration using normal hepatic tissue as control, to observe the serial histological findings after ethanol injection, and to determine the influence of the ethanol on survival days with VX2 cancer of the liver. The necrotic area caused by ethanol showed a significant dose-dependent correlation in the range of 0.1-1.0ml in the normal liver, and a significant correlation in the range of 0.2-1.0ml also in VX2 cancer of the liver. Further, VX2 cancer of the liver showed a significant extension in the number of survival days in the injection group after ethanol injection; 39.5 +/- 5.7 days in the injection group, against 29.3 +/- 2.9 days in the control group. In the successive observation of histological findings after injection, fibrosis started from the 3rd-5th day after ethanol injection and showed acceleration after the 7th day. Eosinophilic infiltration was seen in the VX2 cancer group but not among the controls. Since ethanol causes direct necrosis of the injected region, it is suggested that ethanol injection therapy is a potentially effective method of treating cancer of the liver. PMID- 1877835 TI - [Evaluation of continuous intra-arterial infusion chemotherapy after hepatic resection of liver metastases in colorectal cancer]. AB - We retrospectively evaluated continuous intra-arterial infusion chemotherapy after hepatic resection for hepatic metastases of colorectal cancer. From 1982 to 1990, we treated 22 patients with continuous intra-arterial infusion chemotherapy after hepatic resection, and 43 patients with only hepatic resection. 5-FU (250 mg/day) was administered continuously through implantable reservoir immediately after hepatic resection, and continued as long as possible. The total dose of 5 FU administered was 1.75-46.0 g (mean 17.4 g). We divided the patients into three groups: the first was administered a total dose of 5-FU more than 15 g, the next with less than 15 g, and the last with only hepatic resection was not given 5-FU. The 5-FU group receiving more than 15 g showed the lowest rate of hepatic metastasis recurrence. We compared the group showing recurrence within six months after hepatic resection (early recurrent group) with the group evidencing recurrence on and after six months (late recurrent group). In the former group, extra-hepatic recurrence significantly increased, whereas in the latter group hepatic recurrence significantly increased (p less than 0.05). In the early recurrent group, moderately or poorly differentiated adenocarcinoma significantly increased (p less than 0.01). According to the pathological result of pre operative biopsy, one should check for extra-hepatic lesion as much as possible, and choose systemic chemotherapy for the early recurrent group. PMID- 1877836 TI - [Significance of radionuclide examination in hepatic arterial infusion chemotherapy using implantable reservoir]. AB - Technetium 99m macroaggregated albumin (Tc-MAA) perfusion scintigraphy has been performed during hepatic arterial infusion chemotherapy using implantable reservoir. A total of 40 radionuclide (RI) studies were performed on 25 patients with liver metastasis of colorectal origin. Of 40 RI studies, 12 (30%) showed impaired liver perfusion. Three studies showed no perfusion of the liver, 3 increased radiotracer accumulations at liver hilus, 2 extrahepatic distributions, 2 catheter occlusions, 1 extravasation and 1 unilobar distribution. The accumulation of Tc-MAA in the tumor was graded from Grade I (tumor uptake decreased or similar relative to liver) to Grade III (tumor uptake remarkably increased). The response to chemotherapy was evaluable in 14 cases. A case with Grade I resulted in NC. Of 6 cases with Grade II, 1 resulted in MR, 3 in NC and 1 in PD. Of 8 cases with Grade III, 2 resulted in PR, 1 in MR and 5 in NC. Tumor response was observed in cases showing increased uptake of Tc-MAA. SPECT was performed in 7 cases, and revealed that hepatic tumors were hypervascular. We concluded that RI examination reveals not only hepatic perfusion, but also tumor microcirculation. PMID- 1877838 TI - [A case of malignant hemangioendothelioma effectively treated with intra-arterial continuous infusion of interleukin-2]. AB - An 82-year-old female presented with a tumor in the right-frontal region and was diagnosed as MHE, based on the clinical and pathological findings. Increased LAK (lymphokine-activated killer cell) activity was observed during treatment with intraarterial continuous infusion of rIL-2. In addition, the decrease in tumor size was started when LAK activity became high. Treatments for MHE and mechanism of these therapies were discussed using data from this case and other authors' reports. PMID- 1877837 TI - [Role of oxygen species and lipid peroxidation for anti-tumor effect of intra arterial injection with degradable starch microspheres]. AB - The role of superoxide and lipid peroxidation for anti-tumor effect of intra arterial injection with degradable starch microspheres (DSM) was investigated in rabbits. The anti-tumor effect of intra-arterial injection with DSM was studied in rabbits with VX2 carcinoma of the hind leg. The tumor growth in rabbit treated with DSM 5 times was completely suppressed, and thiobarbituric acid (TBA) reactive substances in the tumor tissue treated with DSM were significantly increased. But the anti-tumor effect of DSM and the increase in TBA reactive substances in the tumor tissue treated with DSM were significantly inhibited by treatment with superoxide dismutase combined with catalase. These results suggest that the anti-tumor effect of intra-arterial injection with DSM may be due to ischemia-reperfusion injury and that active oxygen species and lipid peroxidation may play an important role in the anti-tumor effect of intra-arterial injection with DSM. PMID- 1877839 TI - [Prevention of local recurrence after sphincter-saving resection for rectal cancer]. AB - The main cause of local recurrence after curative operation for rectal cancer is intra-operative implantation of viable shed cancer cells. The present study was undertaken to investigate whether irrigation of remnant rectum prior to anastomosis would prevent local recurrence in rectal cancer. Remnant rectum was irrigated 20 times with physiologic saline using 30 ml enema syringe. One hundred thirty-five patients with rectal cancer underwent sphincter-saving resection for cure. Twenty-six of these patients, received irrigation with physiologic saline, and the remainder received no irrigation. Viable cancer cells were still present in remnant rectum after irrigation 10 times, but absent after 20 times. Distribution by age, sex, stage and the distal clearance margin was similar in both groups. Local recurrence occurred in none of the irrigation-treated patients and in 11 percent of the untreated ones (p less than 0.05). Our results indicate that irrigation 20 times with 30 ml of physiologic saline of the remnant rectum prior to anastomosis is an effective method of preventing local recurrence after resection of rectal cancer. PMID- 1877840 TI - [Intra-arterial infusion chemotherapy for locally advanced breast cancer using implantable reservoir connected with catheter inserted in recurrent radial artery]. AB - Intra-arterial infusion chemotherapy through a catheter incubated at the recurrent radial artery and connected to an implantable reservoir was performed in eight patients with supraclavicular lymph node metastasis including four locally advanced recurrent breast cancers and two inflammatory breast cancer. Clinical response in breast cancer patients was 1 CR, 3 PR, 1 NC, and 1 PD. There was no complication related with catheter insertion. Therefore from the aspect of quality of life, this system was considered useful for treatment of advanced breast cancer, especially locally advanced recurrent breast cancer. PMID- 1877841 TI - [Two cases of stage IV breast cancer with locally advanced lesion treated by intra-arterial infusion chemotherapy using implantable reservoir]. AB - Intra-arterial infusion chemotherapy was used for 2 cases of Stage IV breast cancer with locally advanced lesions using implantable reservoir. The first case is a 64-year-old female who had multiple bone metastases with locally advanced breast lesion. A total dose of 220 mg ADM was injected via reservoir at outpatient department. The other case is a 66-year-old female who had multiple bone metastases with locally advanced breast lesions. A total dose of 235 mg ADM was injected via reservoir. After obtaining satisfactory response of local lesions, a standard radical mastectomy was performed for both cases. It was concluded that this method was useful for controlling locally advanced lesions of Stage IV breast cancer and beneficial for patient QOL. PMID- 1877842 TI - [Infusion of LAK cells and anticancer drugs with a total implantable port to a patient with metastatic liver and spleen tumors]. AB - A case of hepatic and splenic metastases of lung cancer infused with LAK cells and anticancer drugs from hepatic artery with total implantable port (Port-A Cath: Pharmacia, Incorp.) was reported. A 56-year-old male was admitted to our hospital because of general fatigue, jaundice, pleural effusion and elevation of transaminase caused by hepatic and splenic metastases of lung carcinoid. Abdominal ultrasonography revealed 6 hepatic metastatic foci 10-35 mm in diameter and splenic metastases. The patient received 5 courses of MMC infusion, CPA (2 courses) and epirubicin, CDDP (3 courses), and 5 courses of LAK cells (total 1.4 x 10(10)) with IL-2 and OK-432. Eight months after initiation of treatment, jaundice and pleural effusion disappeared, transaminase returned to the normal level and the condition of the patient improved. Although the response of hepatic metastases to the treatment was NC, the size of a splenic metastasis decreased from 35 x 55 mm to 24 x 35 mm (PR). PMID- 1877843 TI - [Regional immunochemotherapy for liver metastasis of esophageal cancer in a patient with variant hepatic artery]. AB - A patient with metastatic liver tumor from esophageal cancer having an anomaly of the hepatic artery was treated by regional immunochemotherapy using two infuserports, which were implanted transfemoral to the right and the left hepatic artery, respectively. The schedule of this therapy was as follows: CDDP (30 mg/m2) on day 1 and 8, 5-FU (1,000 mg/m2) on day 1, 2, 8, 9, 15 and 22, and OK 432 (1 KE/body) on day 3-6, 10-13 and 16-20 were administered via the hepatic artery; and OK-432 (5 KE/body) was also injected intramuscularly three times a week. After the first course of this therapy was performed via the left hepatic artery, metastatic foci in the left lobe regressed, while those in the right lobe progressed markedly. Thereafter, the second course was performed via the right hepatic artery, and then the third course was via both right and left hepatic artery. Following these trials, metastatic foci of the right and the left lobes showed remarkable regression. These results suggest that the effect of immunochemotherapy is closely related with the local concentration of anti-cancer agents. PMID- 1877844 TI - [Superior mesenteric arterial infusion chemotherapy against intestinal obstruction caused by peritoneal carcinomatosis]. AB - For 4 patients with peritoneal carcinomatosis who had severe abdominal pain and vomiting, intra-arterial infusion chemotherapy, via the superior mesenteric artery was performed. After the treatment, all patients were free of their symptoms and began to eat again. Severe complications such as superior mesenteric arterial thrombosis did not occur. It is concluded that our treatment is clinically useful because the quality of life of these patients at the end stage was improved. PMID- 1877845 TI - [Interstitial hyperthermia (MINERVE) for perineal local recurrence of rectal cancer]. AB - Interstitial hyperthermia (MINERVE) was performed for 2 patients with perineal local recurrence of rectal cancer. The MINERVE was a 20 W generator of 550-610 kHz with 4 pairs of probes creating an electromagnetic field (Odam Co., France). The basic regimen was five irradiation treatments of 2 Gy per week, with two hyperthermia treatments (for 60 minutes at more than 43.5 degrees C) a week, 500 mg of 5-FU or 25 mg of CDDP per hyperthermia treatment, and 3 g/day of PSK. The radiation therapy was performed prior to hyperthermia, the chemotherapy at the same time. Perineal tumors and symptoms disappeared completely in 1 patient and were reduced in 1 patient. This treatment is expected to be clinically as a part of multidisciplinary treatment for superficial malignant tumors. PMID- 1877846 TI - [Intra-arterial infusion chemotherapy for advanced bladder cancer and prostate cancer using reservoir system]. AB - Eight patients with bladder cancer and two patients with prostate cancer were given intra-arterial infusion chemotherapy using the reservoir system. The tip of the catheter was inserted through the femoral artery to the common iliac artery and we compressed both femoral arteries during infusion. Five patients with locally advanced bladder cancer and two patients with prostate cancer were evaluated for the clinical and pathological efficacy of the treatment. Clinically, the efficacy of four of the five patients with bladder cancer was CR or PR and pathologically (according to Shimosato's criteria), the efficacy was two in IVb or III, and three in IIb. Clinically, the efficacy in two patients with prostate cancer was CR or PR, and pathologically the efficacy was IVb or IIb. Three patients had complications of the reservoir system. These results suggest that good therapeutic efficacy and an improved quality of life can be obtained by intra-arterial chemotherapy using the reservoir system. PMID- 1877847 TI - [Assessment of tissue platinum concentration, X-ray computed tomogram, and microangiography after CDDP intraperitoneal administration in VX2 ovarian tumor]. AB - After intraperitoneal administration of cis-diamine-dichloroplatinum, tissue Pt concentration, dynamic CT, and microangiography were estimated in white rabbit model having been transplanted with VX2 ovarian tumor. The high Pt concentration resulting from CDDP intraperitoneal administration was recognized in kidney, liver, and VX2 ovarian tumor. CT scans demonstrated that CDDP administration inhibited the development of VX2 tumor, revealing the appearance of small areas with no enhancement corresponding to necrotic regions in the tumor external rim. A tumor time-density curve showed a significantly delayed washout of the excretory phase following CDDP administration. Regarding microangiography models, tumor vessels of less than 30 microns decreased. It was suggested that the tumor microcirculation diminished because of the increased tissue pressure concomitant with tumor necrosis. PMID- 1877848 TI - [Intraperitoneal chemotherapy through implantable injection port in patients with advanced ovarian (or tubal) carcinoma]. AB - A total of 38 cycles of intraperitoneal chemotherapy through implantable injection port were carried out in 9 patients with advanced or recurrent ovarian (tubal) carcinoma. The combination chemotherapy consisted of cisplatin 100 mg or carboplatin 450 mg, 5-FU 500 mg and OK-432 10 KE was administered every four weeks for a total of six cycles. Clinical response was evaluated after chemotherapy. Of the eight evaluated patients (in one patient chemotherapy is not completed yet), 1 had complete response, 3 partial response, 2 stable disease and 2 progressive disease. Therapy-related toxic effects were moderate, consisting chiefly of myelosuppression that seemed dose limiting. PMID- 1877849 TI - [Prevention of scald injury due to intraperitoneal hyperthermic perfusion for far advanced gastric cancer]. AB - In an attempt to prevent scald injury on the peritoneo-serosal surface due to intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastric cancer patients, a histamine H2-receptor antagonist, cimetidine, was prescribed for 9 patients. The IPHP treatment was carried out with a closed circuit using a heated perfusate, and intra-abdominal temperature was kept over 44 degrees C throughout IPHP, for 120 minutes. Of 18 patients given IPHP, 9 were administered intravenously cimetidine at a dose of 50 mg/kg just before IPHP (cimetidine group) and the remaining 9 were prescribed IPHP and not given cimetidine (control group). Amounts of exudate and protein from peritoneal cavity and serum histamine were compared between the two groups. The amount of intra-abdominal exudate was 768 +/- 95 ml for 24 hours in the control group, against 408 +/- 75 ml in the cimetidine group. The protein amounts in exudate throughout IPHP were 62.5 +/- 23.5 g in the control group, against 15.9 +/- 5.4 g in teh cimetidine group. Both the exudate and protein amounts were significantly decreased in the cimetidine group, compared with the controls (p = 1.416 x 10(-7), p = 5.358 x 10(-5)). Serum histamine levels in the cimetidine group increased 2.5 to 6.5 fold for over 12 hours after IPHP, compared to those in the control group. These findings suggest that cimetidine suppresses scald injury on the peritoneo-serosal surface by competitive inhibition with histamine. Consequently, histamine originated from the scald region was released into the circulating blood. Thus, cimetidine helped to prevent thermal injury due to the IPHP. PMID- 1877850 TI - Future of specialist journals. PMID- 1877852 TI - Clinical signs of early osteoarthritis: reproducibility and relation to x ray changes in 541 women in the general population. AB - The definition and classification of early clinically apparent osteoarthritis both in clinical situations and in epidemiological surveys remains a problem. Few data exist on the between-observer reproducibility of simple clinical methods of detecting hand and knee osteoarthritis in the population and their sensitivity and specificity as compared with radiography. Two observers first studied the reproducibility of a number of clinical signs in 41 middle aged women. Good rates of agreement were found for most of the clinical signs tested (kappa = 0.54-1.0). The more reproducible signs were then tested on a population of 541 women, aged 45-65, drawn from general practice, screening centres, and patients previously attending hospital for non-rheumatic problems. The major clinical signs used had a high specificity (87-99%) and lower sensitivity (20-49%) when compared with radiographs graded on the Kellgren and Lawrence scale (2+ = positive). When analysis was restricted to symptomatic radiographic osteoarthritis, levels of sensitivity were increased and specificity was lowered. These data show that certain physical signs of osteoarthritis are reproducible and may be used to identify clinical disease. They are not a substitute for radiographs, however, if radiographic change is regarded as the 'gold standard' of diagnosis. As the clinical signs tested seemed specific for osteoarthritis they may be of value in screening populations for clinical disease. PMID- 1877851 TI - Dietary fish oil and the severity of symptoms in patients with systemic lupus erythematosus. AB - A prospective, double blind, cross over study assessing the effects of a low fat, high marine oil diet in 27 patients with active systemic lupus erythematosus has been performed. The patients were given 20 g daily of MaxEPA (eicosapentaenoic acid) or 20 g of olive oil (placebo) in matching capsules added to a standardised isoenergetic low fat diet. When individual outcome measures of the 17 patients who completed the full 34 week study were considered 14 who were receiving MaxEPA achieved useful or ideal status, whereas 13 receiving placebo were rated as worse or no change. The difference between the two types of capsule was statistically significant. No major side effects were noted, and it is suggested that dietary modification with additional marine oil may be a useful way of modifying disease activity in systemic lupus erythematosus. PMID- 1877853 TI - Two methods of assessment of methotrexate hepatotoxicity in patients with rheumatoid arthritis. AB - Serial liver biopsy specimens from 18 patients with rheumatoid arthritis receiving a weekly dose of methotrexate 7.5-20 mg for a minimum of 12 months were assessed semiquantitatively and by a microcomputer image analysis system. The semiquantitative histological method showed a significant increase in pericellular collagen and in overall disease while morphometry showed a significant increase in pericellular, perivenular, and portal tract collagen. There was a significant correlation between the two methods, but morphometry had the advantage of objectivity and efficiency. There was no correlation between the increase in collagen and the accumulated dose of methotrexate, which suggests that other factors in addition to methotrexate may contribute to liver injury. PMID- 1877854 TI - Different training patterns and bone mineral density of the femoral shaft in elite, female athletes. AB - The effects of sporting activity and of menstrual status on the bone mineral content of the femoral mid-shaft were investigated. The cohort consisted of 67 elite, female athletes comprising 21 runners, 36 rowers, and 10 dancers. Twenty five of these athletes were amenorrhoeic, 27 eumenorrhoeic, and 15 were taking the oral contraceptive. The bone mineral content was also measured in 13 eumenorrhoeic, sedentary women. The mean (95% confidence interval) bone mineral content in the runners was 1.51 (1.47 to 1.55) g/cm2, which was significantly higher than in the rowers, dancers, and sedentary controls whose values were 1.43 (1.40 to 1.47), 1.39 (1.33 to 1.45), and 1.40 (1.34 to 1.45) g/cm2 respectively. There was no significant difference in the bone mineral content between the amenorrhoeic, eumenorrhoeic, and oral contraceptive taking athletes. These results may have implications for devising exercise strategies to reduce the possibility of fractures in later life. PMID- 1877855 TI - High prevalence of systemic disease and mortality in Asian subjects with systemic lupus erythematosus. AB - All patients with systemic lupus erythematosus (SLE) (American Rheumatism Association criteria with positive antinuclear antibody titre) and who attended any of the three general hospitals in Leicester over a 10 year period were ascertained using several complementary sources. Eighty seven subjects (26 Asian, 61 white) were identified. The estimated prevalence of SLE in Leicester is 0.4/1000 for Asian and 0.2/1000 for white subjects. Mean age of onset of the disease was 24 years in Asian and 31 years in white subjects, with both groups showing a female preponderance. Proteinuria (greater than 1 g/24 h) was noted in 15 (58%) Asian and 21 (35%) white subjects; neuropsychiatric disease in 10 (38%) Asian and 8 (13%) white subjects; myalgic symptoms with raised muscle enzymes in 9 (35%) Asian and 3 (5%) white subjects. Nineteen (73%) Asian subjects were positive for extractable nuclear antigens as well, at some stage of their disease, compared with 6 (10%) white subjects. Immunosuppressive treatment was required in 12 (46%) Asian and 12 (20%) white subjects, and deaths of seven Asian and five white subjects were attributed to SLE. These findings show that Asian subjects have a higher prevalence of SLE with greater systemic disease and mortality. PMID- 1877857 TI - Rheumatology in the past. PMID- 1877856 TI - Distribution of type VI collagen expression in synovial tissue and cultured synoviocytes: relation to fibronectin expression. AB - Type VI collagen has recently been shown to be an important component of connective tissue. Double label immunofluorescence procedures were used to immunolocalize type VI collagen in normal and rheumatoid synovium and its distribution was compared with that of fibronectin. In normal synovium type VI collagen is expressed in the synovial membrane but not in the interstitium of the villus. In rheumatoid synovium, however, type VI collagen is extensively deposited in both the interstitial connective tissue and along the lining of the synovial membrane. Cultured rheumatoid and normal synoviocytes produce type VI collagen and fibronectin and incorporate them into their extracellular matrix. These data suggest that type VI collagen may play a part in matrix remodelling of the inflamed joint. PMID- 1877858 TI - Rheumatology in the future. PMID- 1877859 TI - Combination chemotherapy in rheumatoid arthritis. PMID- 1877860 TI - A note on the history of the journal. PMID- 1877861 TI - History of books and journals and periodicals in rheumatology. PMID- 1877862 TI - Art, history, and rheumatism: the case of Erasmus of Rotterdam 1466-1536 suffering from pustulotic arthro-osteitis. AB - Pustulotic arthro-osteitis probably associated with retroperitoneal fibrosis has been diagnosed in Erasmus of Rotterdam, based on paintings of Quentin Massys (1517) and Hans Holbein the younger (1523), historical letters of Erasmus, and postmortem examination of the skeleton. This case report is a description of the earliest known case of pustulotic arthro-osteitis, a syndrome reported for the first time in 1967 and seen more commonly in Japan than in Europe. Works of art of many different kinds may provide an important source of evidence of disease and contribute to a better understanding of the natural history of a disease. PMID- 1877864 TI - Cryptosporidial enteritis complicated by conjunctivitis. PMID- 1877863 TI - Quality assurance and audit: lessons from North America. PMID- 1877865 TI - Drugs and the elderly. PMID- 1877866 TI - Raised plasma concentrations of endothelin-1 in systemic lupus erythematosus. PMID- 1877867 TI - Mycoplasmas and human arthritis. PMID- 1877868 TI - [Effect of low molecular weight regulators on the biosynthesis of rifamycin B by Amycolatopsis mediterranei strains]. AB - Formation of differentiation regulators of the A-factor group in representatives of Nocardia and Nocardia-like actinomyces: N. asteroides, N. brasiliensis, Amycolatopsis mediterranei and "Streptomyces listeri" was observed. The effect of the regulators of different nature (barbital, A-factor and B-factor) on biosynthesis of rifamycin B by A. mediterranei strains was studied. It was shown that the A-factor stimulated rifamycin B production in the adifferentiated low active variant isolated from a natural population of the active strain VNIIA 1713 of the rifamycin B-producing culture. B-Factor insignificantly inhibited biosynthesis of rifamycin B in the studied strains of A. mediterranei. PMID- 1877869 TI - [A system for screening natural immunosuppressors]. AB - Criteria for directed screening of antibiotics with immunosuppressive action were defined. The first stage included screening of cultures producing antiaspergillous antibiotics. At the second stage, the antibiotics whose antifungal activity decreases in the presence of insulin (at the background of calcium salts) and erythromycin and increases in the presence of verapamil were selected. The screening of antibiotic-producing cultures among 123 strains of mycelial fungi and 181 strains of actinomycetes resulted in isolation of 3 fungal cultures and 2 actinomycetes which produced antibiotics corresponding to cyclosporine A as evidenced by thin-layer and high performance liquid chromatographies. PMID- 1877870 TI - [A new approach to the search for antineoplastic compounds]. AB - The necessity of using microbial test systems with regular reproduction of associated impairments in cell differentiation and division in screening of antitumor compounds is substantiated. Conditions for induction of such impairments during secondary growth in prokaryotic and eukaryotic mycelial microorganisms were developed. The fungal culture, Fusarium bulbigenum var. blasticola, the growth of whose secondary colonies was selectively inhibited by representatives of various classes of antitumor agents such as alkylating agents, antimetabolites, antibiotics, plant preparations, etc. was isolated. PMID- 1877871 TI - [Structure-activity relationship in cephalosporin antibiotics. I. Impact of nitrogen functions on biological activity of cephalosporins--7 aminocephalosporanic acid derivatives]. AB - The impact of the nitrogen containing functional groups of the radical at position 7 in the cefem nucleus on antimicrobial activity of cephalosporins against gram-positive and gram-negative organisms was studied. 235 compounds were tested. It was shown that the presence or absence of the above mentioned functional groups could not be used as the only factor for estimating the pharmacological properties of the antibiotics under investigation. There were different and, occasionally, diametrically opposite effects of the spatial arrangement of the nitrogen-containing descriptors on gram positive and gram negative organisms. It was concluded that prediction of the biological activity of cephalosporins by the pattern recognition according to the presence and spatial arrangement of the functional groups was possible. A way for designing novel compounds with the required biological activity is proposed. PMID- 1877872 TI - [Structure of heliomycin produced by Streptomyces heliomycini and antibiotic 11 98 produced by Streptomyces olivocinereus]. AB - The data on UV, 1H NMR and mass spectroscopy confirmed that heliomycin produced by S. heliomycini and antibiotic 11-98 produced by S. olivocinereus were identical with resistomycin. The major minor component produced by S. heliomycini was shown to be resistoflavin which was also confirmed by physicochemical methods. PMID- 1877874 TI - [Aminoglycoside-inactivating enzymes in strains of Salmonella and genes encoding them]. AB - Aminoglycoside resistance patterns of 56 strains isolated from man, cattle and environment were determined. 34 out of 42 gentamicin-resistant strains were shown to produce AAC(3)-II and 7 strains produced ANT(2"). All the 48 kanamycin resistant strains produced APH(3')-I. Spot hybridization of the 42 gentamicin resistant strains with the inner fragment of the aacC2 gene revealed positive signals for all the strains. Hybridization of the 48 kanamycin-resistant strains with the aphA1 gene probe provided positive results in all the strains. The AAC(3)-IV encoding gene was not detected by DNA-DNA hybridization in the strains studied. PMID- 1877873 TI - [Prospects for using DNA probes for rapid diagnosis of antibiotic resistance in clinical strains of enteric bacteria]. AB - Aminoglucoside resistance patterns of clinical strains of enteric bacteria isolated from inpatients of Moscow clinics were determined. APH(3')-I and AAC(3) II were shown to be the most frequent. The aphA1 and aacC2 genes encoding the enzymes were cloned from the R plasmid of the transconjugant of the E. coli clinical strains. DNA probes based on the determined nucleotide sequences of the cloned genes were constructed and used in DNA-DNA hybridization experiments. The results on the occurrence of APH(3')-I and AAC(3)-II in the strains tested were confirmed by the DNA-DNA hybridization. Prospects for developing a set of DNA probes for rapid diagnosis of antibiotic resistance are discussed. PMID- 1877875 TI - [Some aspects of antibiotic resistance of oligotrophic bacteria]. AB - Antibiotic resistance spectra of a large group of oligotrophic and eutrophic bacteria from the open soil and aquatic ecosystems were studied. It was shown that sometimes antibiotic resistance of the oligotrophs was of plasmid nature. A possible transfer of plasmid antibiotic resistance from oligotrophs to pathogenic eutrophic soil and aquatic bacteria in the natural ecosystems is discussed. It was demonstrated that there was no insurmountable transcription/translation barriers between oligotrophic and eutrophic bacteria though the two bacterial groups are taxonomically and evolutionally very distant. A hypothesis was proposed that oligotrophic bacteria are likely to be one of the possible pools of plasmid antibiotic resistance for pathogenic microbes. Plasmid-free strains of some oligotrophic bacteria were selected. With the method of antibioticograms, taxonomic patterns for oligotrophic bacteria of the central group were developed. PMID- 1877876 TI - [High performance rapid method for estimating the sensitivity of viruses to synthetic compounds]. AB - A high performance semiautomatic microprocedure was used. It provided reliable quantitative estimation of antiviral and toxic properties of synthetic compounds. The procedure is rapid, technologically simple and cost-effective. PMID- 1877877 TI - [Comparative study of the effect of daunorubicin and its nitroxyl derivative on in vitro function of rat liver mitochondria]. AB - The effect of rubomycin (daunorubicin) and its nitroxyl derivative, ruboxyl, on respiration and oxidative phosphorylation of the rat liver mitochondria was comparatively studied. It was shown that ruboxyl had a more pronounced uncoupling effect than rubomycin, especially during respiration in the presence of the glutamate mixture with malate. Unlike rubomycin, ruboxyl in concentrations of 0.05 to 0.5 mM induced stimulation under metabolic conditions rather than respiration. When the antibiotic concentration increased ruboxyl started to inhibit the respiration as compared to the control and the inhibition level appeared to be higher than that induced by rubomycin. Possible mechanisms for decreasing rubomycin toxicity by its modification with the nitroxyl radical are discussed. PMID- 1877878 TI - [Multifactorial experiment on the combined action of doxycycline and a low molecular weight immunomodulator of microbial origin in experimental anthrax infection]. AB - Chemotherapeutic efficacy of combined therapy of experimental anthrax infection with subtherapeutic doses of doxycycline and a low molecular weight immunomodulator of microbial origin was studied with mathematical design of the experiment and multifactorial analysis. A marked synergistic effect of oral doxycycline and the immunomodulator was observed. The results of the multifactorial experiment were computer processed and polynomial statistic models (the second order equations) describing the survival rate and mean lifespan (MLS) were derived. The equal level lines characterizing the survival rate and MLS were plotted against the fixed values of the time factor of administering the immunomodulator and the dose of the antibiotic. The doses of the immunomodulator and the time of its administration were optimized with respect to the maximum therapeutic effect with doxycycline subtherapeutic doses. PMID- 1877879 TI - [Experimental study of the pharmacokinetics of an amphotericin B derivative]. AB - Absorption, distribution and excretion of a new water soluble derivative of amphotericin B (NWSDA) were studied after its administration by different routes. After the antibiotic intravenous administration the therapeutic concentrations in blood, organs and urine were shown to remain for prolonged periods. The likely sites of NWSDA deposition were detected with microbiological and radionuclide methods. The most prolonged periods of antibiotic preservation were stated in the renal cortex, spleen and lungs. The ways of NWSDA excretion were studied in operated animals. Only 3.5 per cent of the antibiotic was excreted with urine and bile for 24 hours. The pharmacokinetic parameters of NWSDA after its intravenous administration were estimated. The bioavailability of the antibiotic after its intramuscular and oral administration was found to be low. PMID- 1877880 TI - [Validation of a new procedure for calculating tissue/blood distribution coefficient]. AB - An economic procedure for calculating the tissue/blood distribution coefficient (Kp) for physiological models of pharmacokinetics is substantiated. It stems from evaluation of Kp vs. the drug concentration in tissue and blood specimens. The estimate of the time for collecting biosubstrates for assay of the drug content in them is inverse of the constant of the blood drug elimination rate: Kp = Ct/Cb, where Ct and Cb are the drug concentrations in tissues and blood at the time moment equal to 1/kel. In this procedure the estimates of Kp agree with the values calculated by the AUC procedure which is the most exact but much more labour-consuming. PMID- 1877881 TI - [Impact of nitrogen assimilation on regulation of antibiotic production in Streptomyces hygroscopicus 155]. AB - The enzymes of the assimilation pathways in cultures of S. hygroscopicus grown in the presence of various nitrogen sources were investigated. No assimilation activity of glutamate dehydrogenase (GDH) was observed. Activities of alanine dehydrogenase (ADH), GDH, glutamine: 2-oxoglutarate aminotransferase (GOGAT) and glutamate synthetase (GS) were studied. High concentrations of ammonium and alanine induced ADH formation. The levels of GS remained low in media with NH4Cl. Various nitrogen sources had no impact on the activity of GOGAT which suggested the involvement of constitutive synthesis. ADH was likely to play an alternative role. Determination of the quantitative and qualitative composition of the free amino acids confirmed the involvement of the GS-GOGAT pathway in nitrogen assimilation. The concentration of ammonium ions in the media with one amino acid or in the presence of several amino acids lowered the antibiotic activity while in the media with alanine and the other nitrogen compounds it increased the antibiotic activity. PMID- 1877882 TI - [Biological sensors, their use in medicine and biotechnology]. PMID- 1877883 TI - [Cytologic control of protoplast formation and regeneration in Streptomyces erythraeus, strain BTCC-2]. AB - Experiments on protoplast formation and regeneration in S. erythraeus, strain BTCC-2 (Saccharopolyspora erythrae) were performed under microscopic control at all the stages. It was shown that the highest protoplast titer was provided by the mycelium grown in one step in the absence of glycine. For characterizing the protoplasts formed by the mycelium grown under different conditions, their regeneration capacity was estimated by microscopic examination of the protoplasts after 15-20-hour growth in microchambers and evaluation of the regeneration efficiency 7-10 hours later. Of interest was the fact of spontaneous development of colonies consisting of the protoplast-like cells (L-cells) in 15-20 hours. Such colonies were formed only by the protoplasts grown from the mycelium incubated in one step in the absence of glycine or in the presence of 0.1 per cent of glycine. Such conditions provided also the maximum efficiency of the protoplast regeneration. The long-term storage of protoplasts led to a decrease in their viability. PMID- 1877884 TI - The free nucleocapsids of the viral haemorrhagic septicaemia virus contain two antigenically related nucleoproteins. AB - A protein of 34 kDa (Nx) was induced in vitro by the infection of fish cell cultures with the rhabdovirus agent of viral haemorrhagic septicaemia (VHS) of the trout. This protein only appeared as a major component in concentrated or intracellular labeled VHS virus but not in purified VHS or in the related infectious haematopoietic necrosis virus. That Nx protein is antigenically related to the nucleoprotein of purified virus was shown by its reaction with four anti-nucleoprotein monoclonal antibodies (at least 3 of them reacting non competitively against different epitopes) and by immunoprecipitation with polyvalent international reference sera. The Nx protein was shown to be specifically associated with free non-infective particles isolated by ultracentrifugation which were confirmed to be nucleocapsids by electron microscopy. PMID- 1877885 TI - Eye pathology associated with measles encephalitis in hamsters. AB - Measles encephalitis was produced in 41 hamsters by intracerebral injection of the hamster-neuroadapted Mantooth HBS viral strain. Group I (n = 10) included 2 day old (newborn) hamsters, each inoculated with 0.02 ml of 1:20 diluted virus. This group was sacrificed 4 days postinoculation (DPI). Group II (n = 31) included 25-day old hamsters, each inoculated with 0.03 ml of 1:10 diluted virus. This group was sacrificed 6, 13, 17, and 31 DPI. Clinical and histological evidence of measles encephalitis was present in all infected hamsters. Retinal lesions varied with the age of the animals at the time of inoculation. Retinal folds were observed in the 2-day old group and represented one form of retinal dysplasia. In the 25-day old group, however, earliest retinal involvement was in the form of hemorrhages, followed by focal retinitis in animals sacrificed 6-17 DPI. Measles keratitis was noted only in animals sacrificed 6 DPI. In 25-day old hamsters, measles keratitis and retinal hemorrhages represented the acute manifestations, whereas retinitis occurred later. However, ocular involvement did not correlate with the degree of severity of measles encephalitis. PMID- 1877886 TI - A comparison of the sensitivity and specificity of sialodacryoadenitis virus, Parker's rat coronavirus, and mouse hepatitis virus-infected cells as a source of antigen for the detection of antibody to rat coronaviruses. AB - Sialodacryoadenitis virus (SDAV) and Parker's rat coronavirus (PRC) are two recognized viral strains which cause spontaneous disease in the laboratory rat. Currently there is no recognized practical procedure which will accurately differentiate infections with these strains. Using SDAV- and PRC-infected L-2 cells as the source of antigen, and sera from rats collected post inoculation with either of these viral strains, the indirect fluorescent antibody (IFA) procedure was used to determine whether antibody titers could be used to differentiate infections from the homologous and heterologous virus. There was no detectable difference in the sensitivity or specificity of these systems in detecting antibody to the homologous or heterologous virus. Thus there was no evidence that SDAV- and PRC-infected cells would serve to differentiate antibody to the homologous virus using the IFA technique. In addition, antibody titers were similar when mouse hepatitis virus (MHV)-infected cells were used as the source of antigen for the IFA technique. However, using MHV or SDAV-infected cells as the source of antigen, there was a significant difference in antibody titers to the homologous virus detected using the immunoenzyme technique. PMID- 1877887 TI - Analysis of bovine herpesvirus 4 (DN 599) major antigens with monoclonal antibodies and polyclonal immune serum. AB - Monoclonal antibodies (MAbs) and polyclonal immune sera were produced and used to identify the major antigens of bovine herpesvirus type 4 (BHV-4). SDS polyacrylamide gel electrophoresis of immunoprecipitates of radiolabeled lysates from infected cells resolved 24 peptide bands varying from 12 kDa to over 300 kDa. Six peptides were identified as major viral antigens by immunoprecipitation. Based on the pattern of radioimmunoprecipitation, MAbs were assigned into four groups. Group 1 precipitated a tunicamycin-sensitive glycoprotein complex which contained six components (245, 190, 152, 123, and 48/46 kDa). Deglycosylation with endoglycosidase F revealed two peptides with Mr of 93 and 38 kDa as the basic peptides of the glycoprotein complex. In addition, a 115 kDa glycopeptide containing glycan-peptide bonds of mixed type was identified. Group 2 precipitated a non-glycosylated protein complex consisting of three monomers (33/31/30 kDa). Groups 3 and 4 reacted with single monomeric non-glycosylated peptides with Mr of 48 and 14 kDa, respectively. Although none of the MAbs exhibited significant neutralizing activity, some reacted strongly in immunosorbent and/or immunohistochemical assays, suggesting they may be good candidates for use in diagnostic assays. PMID- 1877888 TI - Amantadine inhibits an early, M2 protein-dependent event in the replication cycle of avian influenza (H7) viruses. AB - Analysis of the effects of amantadine during a single cycle of replication of A/FPV/Rostock virus in vitro showed that, as with other influenza A viruses, an M2 protein-dependent step early in infection was inhibited. No effect was observed on later steps in replication under the conditions used. PMID- 1877889 TI - Proposal for a procedure for complete inactivation of the Creutzfeldt-Jakob disease agent. AB - We have examined complete inactivation conditions on brain homogenates from mice affected with Creutzfeldt-Jakob disease agent, and recommend for routine use a reliable procedure first treating the affected materials with 1 N NaOH for 60 min and then autoclaving at 121 degrees C for 30 min. PMID- 1877890 TI - Ultrastructure of inter-odontoblastic fibres in the rat molar. AB - Radially directed inter-odontoblastic collagen fibres were observed in ultra-thin sections of the radicular pulp/predentine complex of rat molars. Bundles of fibres crossed the distal junctional complexes of the odontoblasts, went through the whole thickness of the predentine and were incorporated into the mineralized dentine. Scanning electron microscopy showed that bundles of radial fibres are not found between the coronal odontoblasts of the rat molar but only in the root. The radial fibres were inserted into the predentine along vertical long-axial crests. The intercrest interval was not tightly fixed and the pattern of fibre bundle insertion did not show a regular periodicity. PMID- 1877891 TI - Temperature dependence of water transport into the mineralized matrix of freeze dried human dentine. AB - Ten dentine sections cut perpendicular to the dentinal tubules from human mature non-carious third molars, were freeze-dried and then rehydrated by immersion in water at four temperatures, 10, 25, 40 and 70 degrees C. The uptake of water by the sections was assessed as a function of rehydration time. The data were analysed using a theoretical model in which the uptake is ascribed to two processes. The first is capillary suction of water into the dentinal tubules, the second is the diffusion of water from the two faces of the section into the mineralized matrix. By fitting theory to experiment the diffusion coefficient of water in intertubular dentine at the different temperatures was found. Using the Arrhenius relation the activation energy of diffusion of water in intertubular dentine was calculated as Ea = 29.5 +/- 2.2 kJ/mol, which is of the order of the strength of a hydrogen bond. Transport of water in the mineralized matrix during rehydration is thus most likely a hopping of water molecules along the surfaces of the collagen and/or mineral, each jump involving the breaking of one hydrogen bond. PMID- 1877892 TI - Functional disturbances of the masticatory system in relation to articulatory disorders of speech in a group of 6-8-year-old children. AB - In the sample of 208 children, clinical signs and symptoms of craniomandibular disorder were mild, somewhat more common in boys than in girls, and clearly more common in children referred for speech therapy than in the control group. Of variables measured in millimetres, the differences indicate sexual dimorphism rather than differences between boys and girls in the occurrence of craniomandibular disorders. The differences may also reflect later maturing of neuromuscular control in boys rather than true differences between boys and girls in the prevalence of craniomandibular disorder. Logistical regression showed that children with articulatory speech disorders had more subjective symptoms and retrusive interferences, smaller maximal opening, and larger maximal laterotrusion and protrusion movements of the mandible than the controls. Thus different dysfunctions of the orofacial region tend to coexist in the same individuals. Subjective symptoms and clinical signs are mild in 6-8-yr-old children and may reflect immaturity of fine motor control. PMID- 1877893 TI - A study of human jaw movements deduced from scratches on occlusal wear facets. AB - In a previous investigation, scratches on tooth wear facets provided information about functional movements of the mandible in the occlusal range. Depending on the type of facet observed, two or three main directions were found. The aim now was to answer two questions: (1) how long does it take for a newly formed scratch to disappear? and (2) do the observed orientations of the scratches change over a long period of time? Eleven wear facets from lower first molars were analysed in four subjects with good natural dentition. Scratches recorded on cellulose replicas were observed under an interference microscope. The same wear facets were recorded one, two, three and six months later. From the photographs of the replicas, a sample of scratches was selected at random and their direction was measured. In the first part of the study, scratches absent at the time of the first observation appeared one month later; 87% of the new scratches had disappeared after one month. Ninety-six percent of the same group of scratches had disappeared after two months. In the second part of the study the angle made by each scratch with the sagittal plane was recorded. It was found that: (1) jaw movements in their occlusal phase can take any possible direction and (2) the distribution of the observed scratches was not random; preferential orientations exist and those present on the working facets are different from those on the non working facets. Similar orientations were identified 6 months later. PMID- 1877894 TI - Growth potential of the rat mandibular condyle as an isogeneic transplant traversing the interparietal suture. AB - The mandibular condyle of 5-, 10- or 20-day inbred male rats was transplanted across the interparietal suture of male litter-mates and the transverse dimension of the neurocranium was measured from dry skulls at 25 or 35 days. The width of the neurocranium had increased significantly from days 5 or 10 to 25 in the rats with the transplants, whereas the difference from controls was small or non existent by 35 days. Histological examination showed that the cartilaginous zone was reduced in the transplants at 25 days but that there were still layers of chondrocytes at 35 days. It is suggested that the rat mandibular condyle is endowed with a tissue-separating, interstitial growth potential that, to some extent, is unrelated to mobility, and essentially effected by chondrocyte hypertrophy. PMID- 1877895 TI - Cyclical changes in pH in bovine developing enamel as sequential bands. AB - Developing enamel was stained with pH indicators and a banded colour pattern exhibiting alternate acidic (5.8-6.0) and neutral (7.0-7.2) staining was clearly visualized. The pH values of the enamel samples scraped from respective bands were confirmed by measuring them in suspensions with a pH meter. Neutral bands corresponded to red stripes of glyoxal bis(2-hydroxyanil) staining and acidic bands to unstained ones, suggested a correlation of the acidic and neutral stripes with the zones of ruffle-ended and smooth-ended ameloblasts. PMID- 1877896 TI - Predicting foodstuff from jaw dynamics during masticatory crushing in man. AB - In previous in vitro experiments using an Instron instrument, each test food was found to have characteristic textural properties. In vivo experiments were now made (1) to determine the degree to which variations in the vertical jaw movements during the crushing phase of mastication can be explained by the inherent properties of the foodstuff being chewed, and (2) to establish the degree to which the foodstuff being chewed can be identified by certain features of the jaw dynamics. Five adults were used for chewing tasks with standardized pieces of beef, carrot or peanut. Each subject made two trials with each foodstuff. The movement of the lower incisal point was monitored; features of movement associated with jaw closing in the first chewing cycle were considered. Five of these features were not suitable to categorize the various test foods. Each of the remaining 4, however, was able to distinguish either one food from the 2 others (2 cases), or one from another (2 cases). Pattern recognition techniques based upon principal component analysis could differentiate jaw closing patterns associated with chewing beef from those involving peanut or carrot. The extent to which peanut could be distinguished from carrot was not as predictable as the categorization of peanut or carrot versus beef. Cross correlation of in vitro force-time breakage characteristics and the jaw movement data showed that on average 52% of the variation in the vertical jaw movement during crushing of food could be explained by the inherent properties of the food.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877897 TI - Infant-adult differences in unmasked thresholds for the discrimination of consonant-vowel syllable pairs. AB - Speech sound discrimination thresholds were obtained for two speech sound contrasts (/ba/ vs. /da/ and /ba/ vs. /ga/) for infant and adult subjects. The stimuli were computer-generated synthetic tokens. An adaptive (one-up, one-down) threshold procedure was used with the visual reinforcement infant speech discrimination procedure for the infant subjects. Adults were tested using the same apparatus and threshold-tracking protocol as the infants. There was a 28-dB difference in threshold for discrimination of /ba/ versus /da/ and a 25-dB difference in threshold for discrimination of /ba/versus/ga/ between the infants and the adults. The differences reveal that to reach a criterion level of performance on a simple speech perception task, infants require much greater stimulus intensity than do adults. This has implications for our understanding of normal auditory development, for our notions of hearing impairment in infants and for the role of intensity in research studies of infant speech perception. PMID- 1877898 TI - Objective measures of sentence level with respect to loudness. AB - The best method for objectively measuring the level of running speech has not yet been established. In the present study, subjective and objective measures of the level of sentence pairs were compared. Psychoacoustic judgments of the loudness of ten sentence pairs were made by ten listeners. The level of the sentences was measured using four objective methods. The purpose was to determine which of the objective measures best matched the psychoacoustic data. The objective methods included: Sound level meter (SLM), percentile level, average power level (Leq) and the loudness calculation procedure according to ISO 532 B. There were no significant differences between the estimates using the SLM set on either 'Impulse', 'Fast' or 'Slow' settings, the Leq, the percentile level Lmax and the percentile loudness Nmax to N30 using conventional calculation techniques. The measures obtained using A-weighting on the SLM were not found to be superior to the unweighted measures. These findings have implications for the measurement of the level of sentences used in clinical audiology. PMID- 1877899 TI - Use and benefit of hearing aids in the tenth decade--and beyond. AB - The purpose of this study was to evaluate the use and benefit of hearing aids in 185 hearing-disabled subjects born before 1900, consecutively fitted with a hearing aid during the first 6 months of 1989. Information from 138 (75%) subjects, 117 females and 21 males with a median age of 93 years (range 90-107), was obtained from a questionnaire, which was mailed 4-6 months after the fitting procedure. The questionnaire included questions concerning use of the hearing aid(s), self-reported benefit, handling problems, overall satisfaction/dissatisfaction, social and domiciliary situation and self-reported visual capacity. Among these elderly subjects 75% had previously been provided with hearing aids, while 25% were first-time users. The results demonstrate that 76% use the hearing aid(s) at home and in small groups, and that 51% use the hearing aid(s) each day; however, 35% did not respond to this question. 64% expressed general satisfaction with their aid(s). Despite instruction and counselling, handling problems were frequently present. In those previously fitted with hearing aids a higher rate of time-related use and satisfaction was present, and handling problems were less frequent than in the first-time applicants. It is concluded that elderly hearing-impaired subjects in the tenth decade use and benefit from hearing aids; however, more problems concerning use and benefit of hearing aids are present in this age group than in the younger age groups. PMID- 1877900 TI - Clinical evaluation of a programmable three-channel automatic gain control amplification system. AB - This paper reports on the clinical evaluation of a commercially available head worn programmable 3-channel automatic gain control (AGC) hearing instrument (Siemens, Triton 3000). A preliminary fitting procedure is developed for the 3 channel AGC amplification system, which is compared by 26 experienced hearing instrument wearers with their own single-channel AGC instruments. The benefits of both amplification systems are assessed by speech audiometry at different signal to-noise ratios utilizing German rhyme test speech material. In addition, subjective judgements concerning sound quality, speech intelligibility and comparison with the subject's own instrument are evaluated. The results indicate that the multichannel compression instrument is superior to single-channel aids in competitive speech situations. If the 3-channel AGC instrument is used as an automatic noise reduction system in patients requiring a certain amount of low frequency gain, a markedly better speech recognition can be achieved compared to the subject's personal aids. PMID- 1877901 TI - Test-retest variability in audiometric threshold with supraaural and insert earphones among children and adults. AB - The effect of age and earphone condition on test-retest intrasubject variability in audiometric threshold was investigated. Ten subjects in each of the following age groups were investigated: 6-9 years, 10-13 years and young adults. Test retest audiometric thresholds were collected at six frequencies (250, 500, 1,000, 2,000, 4,000 and 8,000 Hz) under three earphone conditions (Telephonics TDH-50P supraaural and Etymotic Research ER-3A insert earphone coupled to an immittance probe cuff or a foam insert). No statistically significant differences were found in variability of test-retest differences as a function of age, earphone condition or test frequency (p greater than 0.05). The clinical application of the insert earphone is recommended with children and adults as it affords no greater test-retest variability and at the same time provides a solution to a number of limitations incurred with the use of the supraaural earphone. PMID- 1877902 TI - Binaural masking level differences in children with a history of otitis media. AB - The binaural hearing of children with and without a history of otitis media (OM) was assessed by determining their binaural masking level differences (BMLDs). The test was also administered to a group of adults. BMLDs for the non-OM children were not significantly different from those of adults. However the mean BMLD of the OM children was significantly lower than that of non-OM children. Some children in the OM group had small (15-25 dB HL) sensitivity deficits in one or both ears. However, no correlation was found between BMLD and hearing level in cases of either symmetric or asymmetric loss. Exclusion of OM children with residual middle ear abnormalities did not abolish the significant difference between the OM and non-OM groups. We suggest that the small BMLDs in the OM group may be associated with these children having difficulties detecting and attending to signals in noisy environments. PMID- 1877904 TI - A ten-year follow-up case report following surgical correction of anterior open bite. AB - A case is reported whereby an anterior open-bite was treated with the Kole osteotomy in an adult Chinese girl. This study documents cephalometrically the post-treatment changes occurring in the dento-alveolar complex over a ten year follow-up period and describes the possible mechanisms contributing to the remarkable stability of the open-bite correction. PMID- 1877903 TI - Minimal morbidity in outpatients undergoing oral surgical procedures under general anaesthesia in the dental surgery. AB - Economic pressures have resulted in an increased demand for surgical treatment under general anaesthesia on an outpatient basis. Previous studies have reported a high incidence of severe morbidity associated with general anaesthesia in both general dentistry and oral surgery. This is particularly marked with dento alveolar procedures. The ready availability of relatively inexpensive monitoring equipment together with upgraded standards recently announced by various authorities necessitates that all practitioners review their current practices in the areas of sedation and general anaesthesia. In addition to the ultimate importance of patient care and safety, the increased incidence of litigation leaves no latitude for complacency. This paper details a relatively simple, cost effective general anaesthetic technique suitable for outpatient oral surgical procedures in the dental surgery in which all relevant recommendations at the time of writing were observed or exceeded. Associated morbidity was considerably less than previously reported, with a high degree of patient satisfaction. PMID- 1877905 TI - Eosinophilic granuloma of the oral region: a potential diagnostic problem. AB - Eosinophilic granuloma is a condition which may initially present with oral symptoms. Its variable oral clinical manifestations can result in a potential diagnostic problem for the dental surgeon. Two cases are presented which illustrate the difficulties in making a definitive diagnosis. The importance of a biopsy in diagnosis and the use of a whole-body skeletal scan in formulating a treatment plan are highlighted. PMID- 1877906 TI - The effect of cheese on dental caries: a review of the literature. AB - The relationship between nutrition and dental health has been a topic of interest for many years. Recently, the cariostatic properties of cheese have been the subject of intensive research. Most of these studies suggest that the use of cheese as the final food in a meal will help to reduce caries. Several mechanisms by which cheese may reduce enamel demineralization have been proposed. Chewing cheese stimulates saliva flow. The alkaline nature of saliva buffers the acids formed in plaque. There is also an increased rate of sugar clearance due to the diluting action of cheese-stimulated saliva. Research has also suggested that chewing cheese may reduce the levels of cariogenic bacteria. This may be secondary to the reduced incidence of caries as conditions within a carious lesion tend to promote the growth of these organisms. The high calcium and phosphorus content seems to be another factor in the cariostatic mechanism of cheese. Both casein and whey protein seem to be involved in the reduction of enamel demineralization. Casein phosphopeptides may also be responsible for some anticariogenicity by concentrating calcium and phosphate in plaque. An overview of the effect of milk on dental caries is also presented in this review. PMID- 1877907 TI - The range of functional mandibular movement in bruxists. 3. Results. AB - Part 3 presents the results of the examination carried out in Part 2. A summary of the tooth tapping task and the chewing task is given with comment on the coronal, sagittal, and horizontal plane of bruxists and non-bruxists. PMID- 1877908 TI - Endurance of jaw elevator muscles during cementation of a single molar crown. AB - Muscle activity of four jaw-closing muscles was monitored in 19 healthy subjects by EMG, under conditions associated with cementation of a crown restoration. Each subject performed two maximum voluntary contractions (MVC), each of two minutes duration, separated by a thirty-minute time interval. There was no visual feedback of muscle activity. Local analgesia, psychologic reinforcement and actual cementation were other conditions tested. All muscles fatigued as a function of time. For this experimental procedure the ipselateral muscles demonstrated less endurance than contralateral muscles. Psychologic reinforcement did not alter muscle activity. The effect of local analgesia was inconclusive and requires further investigation. PMID- 1877909 TI - Severe abrasion of composite and amalgam restorations in a patient with lupus erythematosus systemic. Case report. AB - A case of repeated severe abrasion of amalgam and composite resin restorations in a patient under treatment for Lupus erythematosus systemic is reported. The patient had a history of audible nocturnal bruxism. Severe roughening occurred within three weeks of placement of the restorations and was related precisely to surfaces in contact with the opposing restored dentition. Examination by SEM revealed an unusual wear pattern of the amalgam restorations. PMID- 1877910 TI - The dental profession in Hong Kong. PMID- 1877911 TI - Comparison between two procion dyes and alizarin red to assess marginal leakage in resin restorations. A laboratory study. AB - To assess the width of the gaps that may occur in resin restorations bonded to dentine, buccal and lingual cavities were prepared in 18 caries- and restoration free extracted molar teeth. All teeth were restored with composite resin. Nine of the teeth were then thermocycled for five hours. All teeth were stained with 0.5 per cent, 1.0 per cent or 1.5 per cent solutions of chloro-s-triazinyl dyes (Reactive Red and Reactive Orange 14) or Alizarin Red in order to assess the effectiveness of each stain in detecting marginal leakage. Quantitative assessment indicated that Reactive Orange 14 was superior to the other two stains as it more clearly defined the marginal gaps of the restorations. This superiority was evident for both thermocycled and nonthermocycled teeth. PMID- 1877912 TI - Soft tissue calcifications in the differential diagnosis of opacities superimposed over the mandible by dental panoramic radiography. AB - Not all opacities observed on panoramic dental radiographs are associated with the jaws. Two thousand six hundred and twenty-eight panoramic radiographs obtained from a single dental health clinic were evaluated for the presence of opacities associated with the mandible. Opacities were observed in 4 per cent of cases. The radiographic features of these opacities are presented. The importance of including soft tissue calcifications which may be superimposed over the mandible on panoramic views in the differential diagnosis is discussed. Information on the various soft tissue calcifications which can occur in this region is presented. PMID- 1877913 TI - The treatment of facial disharmony and malocclusion by jaw surgery. Case reports. AB - Examples are given of the Australian Cranio-Facial Unit's methods of dealing with facial disharmony and malocclusion by orthognathic surgery. Members of the Unit specialize in different aspects of craniofacial structure and function, and their teamwork is described. Treatment planning and assessment are illustrated by traditional cephalometric and other analytical procedures, and by pattern profile analysis. An appraisal is made of the Unit's increasing use of computer technology to facilitate these analyses, and to integrate various sources of information about facial disharmony. PMID- 1877914 TI - A large dermoid cyst of the neck. Case report. AB - An elderly patient presented with a large asymptomatic submental swelling which had been present for about fifteen years. The clinical diagnosis was a dermoid cyst and the lesion was removed in toto. Histological examination confirmed the clinical diagnosis. Unless such lesions are very large and cause displacement of the tongue, there is usually no associated dyspnoea, dysphagia or dysphonia. PMID- 1877915 TI - Transmigration of permanent mandibular canines. Case report. AB - Transmigration is the migration of a tooth across the midline of the jaw. This phenomenon is found only in relation to the permanent mandibular canines. Two cases are reported. In both, the cause of this deviation was an odontome found in the site normally occupied by the mandibular canine. The literature on transmigration is reviewed. PMID- 1877916 TI - The range of functional mandibular movement in bruxists. 4. Discussion and conclusions. AB - A study of some kinesiological characteristics of the mandible of non-bruxist and bruxist subjects was carried out using a closed circuit television point movement tracking system. The use of incandescent light bulbs attached to the incisor teeth of the maxilla and mandible as the point movement source allowed records to be made without head restraint of the subjects examined. Records were stored on magnetic tape. Mandibular movement was studied using the vertical, lateral and anteroposterior components of movement. Two components of movement were combined electronically for all three combinations of the components and the signals produced were used to prepare envelopes of motion graphically, on an X-Y recorder, in the coronal, sagittal and horizontal planes. Qualitative analysis of envelopes of motion in three planes mutually at right angles proved useful in providing information which demonstrated trends to minor differences between non bruxist and bruxist subjects. However, variations of patterns of movement occurred frequently enough in each test of each group to negate any possibility at present of using these techniques in the development of diagnostic procedures. PMID- 1877917 TI - Replacement of low copper amalgams by a group of general dental practitioners. AB - The replacement of low copper amalgams was studied in a number of general practices in Adelaide in 1975 duplicating, by design, the method of a similar Canadian study. The results of this study are in surprising agreement with the Canadian data, and are still relevant to modern practice as the high copper alloys have not proven to have greatly superior longevity. This study involved 60 dentists who, over 271 working days, replaced an average of 6.7 amalgam surfaces/dentist/day. This is equivalent to 1541 amalgam surfaces replaced/dentist/year. In addition, the reasons given for the removal of existing amalgam restorations were closely congruent with those given by the Canadian dentists. This study also indicated that many of these restorations increased in size. This is evident through restorations extending from two surfaces to involve three surfaces. PMID- 1877918 TI - Comparison of dental needs with the treatments actually received. AB - The main purpose of the study was to determine the types, causes, dental needs, and follow-up treatments of the chief complaints of a socioeconomically disadvantaged population of patients attending a public dental hospital. Around half of the 301 patients examined were 45 years of age and older, and the vast majority were of caucasian origin. The most common dental complaints in 259 patients were toothache, broken teeth, lost fillings, and painful, broken or loose dentures. The most frequent causes of the chief complaints were judged to be dental caries, and inadequate restorations and removable prostheses. On examination, most of the patients also had one or more other unsatisfactory restorations or removable prostheses, especially in the 35 years and over age group. Deep periodontal pockets were also found most often in this age group. After four to six months, of the 259 patients with chief complaints, 113 had had their complaints treated and 45 had not, 47 patients were given a different form of treatment from that proposed, while 31 treatments were uncompleted, and 23 patients could not be followed up. PMID- 1877920 TI - The effects of temperature on the setting of glass ionomer (polyalkenoate) cements. AB - Glass ionomer (polyalkenoate) cements have proved to be superior to zinc phosphate cements as orthodontic luting agents. Setting behaviours at different temperatures were recorded by an oscillating rheometer under controlled conditions. The working time of these cements can be increased by mixing on a chilled glass slab with setting time at mouth temperatures remaining rapid. Where more than one orthodontic band is cemented per mix, the authors recommend refrigeration of the glass slab for at least one hour prior to mixing the cement. PMID- 1877919 TI - Effects of pulsing with xylitol on mixed continuous cultures of oral streptococci. AB - Continuous culture is a means whereby organisms can be grown at rates approaching those occurring naturally. Moreover, the effect of adding transient excesses of various nutrients to the culture vessel ('pulsing') simulates the effect of dietary challenge on dental plaque organisms. Mixed cultures of Streptococcus mutans T8 and Streptococcus milleri B448 were grown glucose-limited in a chemically defined medium under an atmosphere of 5 per cent carbon dioxide in nitrogen, at a dilution rate of D = 0.1 h-1 and controlled pH of 7.0. The level of arginine in the medium reservoir was adjusted so that Strep. milleri predominated over Strep. mutans in a stable coexistence. After equilibration, the culture vessel was pulsed with various carbohydrates to a final concentration of 5 x 10(-2)mol/L. Samples were then taken at regular intervals and differential viable counts of Strep. mutans and Strep. milleri were done on mitissalivarius agar. Results demonstrated that pulsing with glucose, fructose, 'coupling sugar', lactose, xylose and sorbitol gave Strep. mutans a clear ecological advantage. In direct contrast, pulsing with xylitol resulted in a marked antimicrobial effect on Strep. mutans while Strep. milleri was essentially unaffected. This supports recent findings by other workers that uptake of this pentitol by Strep. mutans in batch culture sets up a 'futile cycle', leading to depressed growth or even cell death. PMID- 1877921 TI - Dentist-patient relations. PMID- 1877922 TI - Insisting on policy and protocol. PMID- 1877923 TI - The need for a national task force on dementia. PMID- 1877924 TI - Expert nursing care: some reflections. PMID- 1877925 TI - Used sharps: a hazard in household rubbish. PMID- 1877926 TI - An expensive hobby. PMID- 1877927 TI - Nurse and the law. Disclosing the risks. PMID- 1877928 TI - The third age. Don't give CAM back! PMID- 1877929 TI - Pentamidine. PMID- 1877930 TI - RACS Lecture. The collegiate role in the development of professionalism in the modern community. PMID- 1877931 TI - Comparative study of the role of endo-urological manipulation in the treatment of ureteric calculi using extracorporeal shock wave lithotripsy. AB - The results of treatment of 115 patients with upper and mid-ureteric calculi, using endo-urological manipulation and extracorporeal shock wave lithotripsy were reviewed. The number of shocks administered, the kilovoltage used, the radiation exposure time and the degree of fragmentation achieved were evaluated. Complications occurring in the course of this treatment were also reviewed. A significantly lower number of impulses was required for fragmentation to be apparent at 24 h post-treatment, when the ureteric calculus was able to be manipulated back into the renal pelvis. However, at 6 weeks post-extracorporeal shock wave lithotripsy (ESWL) satisfactory fragmentation was apparent in approximately equal percentages of patients who had undergone successful and unsuccessful manipulation. In addition, a significantly greater mean radiation exposure was used in the treatment of mid-ureteric calculi that could not be successfully manipulated and required treatment in situ within the ureter. These results suggest that treatment of a ureteric calculus in situ within the ureter provides a satisfactory method of fragmentation, although fragmentation takes longer to become apparent than when treatment is undertaken upon a calculus within the renal pelvis. The greater radiation exposure for patients in whom ureteric calculi were treated in in situ within the ureter may reflect the operators' attempts to visualize a change in configuration of the calculus similar to that seen when treatment is given to a stone that has been successfully manipulated. However, since the absence of fragmentation at 24 h post-surgery does not indicate a failed treatment in this group, prolonged screening of the calculus with fluoroscopy may be unnecessary. The complication rate of this method of treatment was low. PMID- 1877932 TI - Radiation therapy for the management of localized prostate carcinoma. AB - Radiation therapy has been reported as an effective modality for the curative management of localized prostate carcinoma. In a 6 year period (1982-87), 141 patients with localized prostate carcinoma were treated at Auckland Hospital. Most patients were given radiation to the prostate alone. The overall local failure rate was 14%, with 57 patients developing distant metastases at the time of analysis. Toxicity was generally acceptable but was clearly related to the size of the treatment volume. The 5 year actuarial survival for all patients was 69.5%. Relapse-free survival rate was 39% at 5 years. Clinical stage and histological differentiation were significant factors affecting survival. Histology was a significant factor in local control. Radiation therapy for localized prostate carcinoma is effective, with a high rate of local control and low morbidity. PMID- 1877933 TI - Polytef paste for urinary incontinence. AB - A series of 28 patients injected with polytetrafluoroethylene (PTFE) (Polytef, Mentor) paste for urinary incontinence is presented. The cystoscopic method of injection was used in 25 patients. Twenty-four adult females with stress incontinence were treated: 10 of these were long-term cures and five improved. Success rates were higher in those who had had previous gynaecological surgery (10 of 12: P less than 0.05) or who had well supported vaginal walls (5 of 5: P less than 0.05). Three adult males were treated, but all failed. Complications including the risk of micro-embolization are discussed. Low morbidity is an attraction and it is concluded that this treatment may have a place for older women with stress incontinence and a well-supported, preferably scarred, anterior vaginal wall. It may be performed under topical local anaesthetic if desired. The availability of a more suitable agent would widen the application of the technique. Subject to long-term experience vindicating early trials, glutaraldehyde cross-linked collagen may be a suitable replacement for PTFE in this role. PMID- 1877934 TI - Detection of gonadal carcinoma in situ in childhood and implications for management. AB - Cells with the characteristic features of carcinoma in situ (CIS) were detected in histological sections of the gonads of three of seven children with clinical syndromes associated with a high risk of gonadal neoplasia. It is suggested that early detection of these cells may be useful in resolving problems of management, including gonadectomy and decisions about sex of rearing. Early detection of CIS cells may have a place in the management of the undescended testis. PMID- 1877935 TI - Preliminary results of conservative treatment of early breast cancer with tumourectomy, axillary dissection and postoperative radiotherapy. A retrospective review of 107 patients. AB - A consecutive series of 107 patients with early breast cancer treated by tumourectomy, axillary dissection and postoperative radiotherapy was retrospectively reviewed. The average age at presentation was 48, range 30-79. Only 23.4% of women were post-menopausal. Average follow-up time was 48 months, range 19-94 months. Eight-three per cent had palpable lesions, the remaining 16.8% had needle localization. Ninety-four patients (88.7%) had lesions less than 2 cm in diameter clinically. One patient had a lesion greater than 3 cm in diameter clinically. Seventy-two per cent had invasive duct carcinoma. Twenty (18.9%) had invasive disease at the margins and fifteen were re-excised. Of the 20 patients who had invasive disease at the margins, three developed local recurrence. True loco-regional recurrence rate (i.e., loco-regional recurrence rate without distant metastasis) was 2.8%. All had level I and II axillary dissections and 26.4% were up-staged from clinical stage 1 to pathological stage II. Five patients died, three with recurrences and two with unrelated disease. Tumourectomy, axillary dissection and postoperative radiotherapy is an acceptable regimen for early carcinoma of the breast. PMID- 1877937 TI - Open subtalar dislocation. AB - Open subtalar dislocation is a rare injury, accounting for about 0.1% of all dislocations and, consequently, the natural history and outcome of this injury and their relevance to treatment are not well documented. A retrospective study at Westmead Hospital revealed 10 patients who presented with this injury between 1978 and 1988. We had the opportunity to review all of these patients in 1987 and again in 1989. We found a high incidence (60%) of poor results, and that the only factor that influenced the outcome was infection. It is concluded that the poor prognosis is due to the nature of the injury itself, rather than any particular factors in the subsequent management. Specifically, there was no relation to the direction of the dislocation, the presence of fractures in the foot, the time elapsed before reduction, or the period of immobilization. PMID- 1877936 TI - Gastrointestinal cancer follow-up: the effectiveness of sequential CEA, TPA and Ca 19-9 evaluation in the early diagnosis of recurrences. AB - One-hundred and seventy-four consecutive patients who underwent curative resection for gastric and colorectal cancer between 1983 and 1985 were studied prospectively to evaluate the roles of sequential carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and Ca 19-9 determinations and independent clinical examinations, in the early diagnosis of resectable recurrences. Sixty six recurrences (33 from gastric and 33 from colorectal cancer) were detected between 6 and 42 months after primary surgery. In gastric cancer CEA, TPA and Ca 19-9 showed a sensitivity of 64%, 73% and 60% respectively and a specificity of 67%, 65% and 54% respectively. Nine patients (27%) underwent surgical treatment for recurrent disease, and four of these (44.4%) had resectable recurrence, for a total resectability rate of 12%. Of these four patients, three are still living after 12, 36 and 44 months respectively from re-operation without evidence of neoplastic disease. In one of these patients, re-operation was performed on the basis of the elevation of the three markers, without any other clinical sign of disease. This patient had a resectable solitary hepatic recurrence. In colorectal cancer. CEA, TPA and Ca 19-9 showed a sensitivity of 73%, 73% and 49% respectively, and a specificity of 77%, 87% and 97% respectively. Fourteen patients (42.4%) underwent surgical treatment for recurrent disease and eight of these (57%) showed resectable recurrence, for a total resectability rate of 24.2%. Six patients are still living after 9, 16, 21, 31, 41 and 53 months respectively from re-operation without evidence of neoplastic disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877938 TI - Physics and function of operating room suction. AB - A study was done to evaluate the performance of suction apparatus in the operating room. The investigation was prompted by perceived poor suction performance in a suite of new operating rooms built in accordance with Standards Australia (SA) specifications. SA performance tests were conducted on each of four suction outlets in nine operating rooms. All 36 outlets complied with SA standards for flow-rate (minimum 40 L/min) and occluded negative pressure (ONP; minimum -60 kPa). However, 24 collection units failed to comply with standards (ONP) of -40 kPa achieved in less than 4 s when a 4 L disposable suction apparatus was connected (mean time to ONP: 6.1 s, 95% confidence interval: 4.9, 7.3). When smaller capacity suction jars were substituted, more units met SA standards. The standards therefore need revision to include specification of the capacity of the collecting apparatus. Other factors that were found to degrade suction performance significantly were air leakage and defective shut-off valves. The physical principles involved in operating room suction are described. Surgeons and anaesthetists should understand these principles, and it is recommended that a simple pre-operative check of the suction apparatus should be carried out, as follows: (1) Turn the wall control knob fully on, and disconnect the suction apparatus. The gauge should register zero. (2) Connect the suction jars. If the indicated gauge pressure is in excess of -15 kPa, investigate the equipment for excessive resistance, particularly in the shut-off valve, which should be replaced with a new unit if necessary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877939 TI - A comparison of standard and rapid infusion methods of liver preservation during multi-organ procurement. AB - The standard and rapid infusion techniques of liver preservation during multi organ procurement were compared in the porcine model of orthotopic liver transplantation. Group I (n = 48) had the standard method of procurement while group II (n = 34) underwent the rapid infusion method. Donor liver function was compared between the two methods using the criteria of survival, liver function tests and histology. No statistically significant difference was evident between the two groups. Because of logistical advantages, the rapid infusion method is recommended as the technique of choice during multi-organ procurement. PMID- 1877940 TI - Prognostic significance of nuclear DNA content in phaeochromocytoma. AB - Nuclear DNA content of 27 phaeochromocytomas was measured by image analysis of thin sections and monolayer smears of nuclei extracted from thick sections (cytospins) using archival paraffin-embedded tissue blocks. Recurrence was assessed on the basis of clinical follow-up or urinary catecholamine levels. The mean follow-up was 5.0 years, with a range of 4 months to 15 years. Although it is not possible to differentiate accurately malignant tumours using DNA analysis, prediction of benign tumours is possible. Using thin sections, all tumours were benign when the percentage of cells with a DNA content of 2.5 c (2 c = diploid) was less than 40% and the DNA content of 5 c was less than 4%. Using the cytospin preparation, all diploid tumours were benign. Thus, patients with diploid tumours may be saved intensive long-term follow-up. Aneuploid and tetraploid tumours, however, continue to require careful lifelong follow-up. PMID- 1877941 TI - Free flap from a non-replantable digit for microvascular digital reconstruction in a multi-digital hand injury. AB - Multi-digit hand injuries require assessment of possible methods of repair and consideration of long-term function to determine the most appropriate management for the individual patient. A case is presented in which an amputated non replantable digit was used as a source of a free flap to cover a large defect on another injured digit. PMID- 1877942 TI - Iatrogenic spinal subdural haematoma. AB - Spinal subdural haematoma is a rare condition, usually seen in association with lumbar puncture or a bleeding disorder. It carries a high morbidity and mortality, and successful treatment requires prompt surgical intervention. We present a case of mixed spinal subarachnoid and subdural haemorrhage complicating failed spinal anaesthesia combined with anti-coagulation in an elderly woman, together with a review of the literature. PMID- 1877943 TI - Multiple hepatic abscesses due to Yersinia enterocolitica. PMID- 1877944 TI - An unusual cervico-laryngeal haemangioma. PMID- 1877945 TI - Hamartoma of the breast. AB - A case of hamartoma of the breast is reported and the literature reviewed. The clinical, radiological and pathological features of this rare condition are discussed, together with the difficulties in diagnosis. Familiarity with this lesion should enable it to be recognized more frequently in future. PMID- 1877946 TI - Torsion of the gall-bladder: rare, unrecognized or under-reported? AB - Four cases of torsion of the gall-bladder are reported. The clinical features closely mimic those of acute cholecystitis. Although conservative management was initially instituted, close monitoring of our patients led to appropriate surgical intervention. Review of the literature suggests that torsion is uncommon. Four surgical registrars at busy district general hospitals seeing four cases in one year suggests that it is under-reported. Acute torsion can develop after a period of recurrent abdominal pain--retrospectively diagnosed as 'chronic torsion'. A prospective study using currently available imaging procedures to assess gall-bladder mobility, itself associated with torsion, could reveal whether this leads to chronic pain. PMID- 1877947 TI - Primary squamous carcinoma of the liver: clinical and histopathological features. AB - A case of primary squamous carcinoma of the liver is analysed in the light of 21 previously reported cases. Symptoms of abdominal pain, weight loss and intermittent fever were in keeping with those most frequently recorded for the tumour type. Histopathological evaluation suggested metaplastic origin from a cholangiocarcinoma. A squamous carcinoma found in the liver need not reflect metastatic spread and primary tumours can be resected if well localized. PMID- 1877948 TI - Fatal haemoperitoneum due to liver metastases from nasopharyngeal cancer. AB - Spontaneous rupture of hepatic metastases is rare, there being only 22 cases documented in the literature. We report here the first such case due to nasopharyngeal carcinomatous metastases. This is of interest because in South East Asia ruptured hepatocellular carcinoma is the usual cause of spontaneous fatal haemoperitoneum. PMID- 1877949 TI - Quality assurance project: treatment outlines for schizoid and schizotypal personality disorders. PMID- 1877950 TI - Psychiatric care of the elderly. PMID- 1877951 TI - Forensic psychiatric services in Victoria. PMID- 1877952 TI - Depression subtyping: unitary, binary or arbitrary? PMID- 1877953 TI - Culture and behaviour of East Asians. PMID- 1877954 TI - Suicide in New Zealand 1957-1986: the influence of age, period and birth-cohort. AB - New Zealand suicide rates from 1957 to 1986 were analysed for age, period and cohort effects. Cumulative suicide rates were relatively stable but more complex patterns were revealed by detailed analysis. There was a steadily increasing rate in young men and a recent increase in elderly men. Reduced mortality rates in equivalent categories of accidental and "undetermined" deaths could have accounted for only a proportion of these increases. A cohort effect was noted in men, with increasing risks of suicide in the young for successive birth-cohorts born from 1947 onwards. In women a period effect was likely, with increasing rates for all age-groups between 1957-61 and 1962-66, followed by a decline recently among all except the youngest age-groups. These trends in women may have been largely due to changes in barbiturate prescribing. In both sexes poisoning declined as a method of suicide, while hanging and carbon monoxide poisoning increased. Firearm suicides also increased in men. The implications of these results for prevention are considered. PMID- 1877955 TI - Sir Burton G. Burton-Bradley. PMID- 1877956 TI - An examination of recent suicides in remote Australia: further information from the Kimberley. AB - Aboriginal suicide has emerged as an issue of public concern only within the recent past. Within the last decade there has been a substantial increase from levels that were previously low. Under the shadow of the Royal Commission into Aboriginal Deaths in Custody these increases, involving primarily young adult males, raise serious questions. Two years ago the author examined a series of suicides that had occurred in one area of remote Aboriginal Australia, the Kimberly region of Western Australia. This paper examines suicides that have occurred in the following two years, with comparisons both with the previous suicides, and with a group of age-matched Aborigines from the general Kimberly population drawn from a random sample survey. PMID- 1877957 TI - The social and family context of aboriginal self-harmful behaviour in remote Australia. AB - In the preceding paper information was presented on a series of recent Aboriginal suicides in the Kimberley region of Western Australia. In this paper the author proceeds to an examination of the social and historical context of these events, which have occurred in conjunction with increases in other violent behaviours. Drawing from information generated by a survey of a stratified random sample of Aborigines from across the region, the rapidly changing environment of childhood is discussed, with particular attention to the structural and functional changes in caretaking roles. The inter-cultural context of these, as yet, largely intra cultural manifestations of disadvantage, are emphasised. PMID- 1877958 TI - Biopsychosocial psychiatry and the criminal justice system: a case report. AB - In criminal proceedings a psychiatrist may be called upon to give evidence as to the state of mind of an accused at the time an alleged crime was committed. Seldom is the psychiatrist able to examine the person at or before the time of the offence and therefore arrives at an opinion by examining the person at some later time. Information gained by this examination is combined with all relevant reports and transcripts concerning the accused, collateral history from friends, relatives or other treating health professionals and the results of any clinical investigations. The psychiatrist ultimately forms an opinion as to the probable state of mind of the accused at the material time. PMID- 1877960 TI - Clonazepam in acute mania: a double blind trial. AB - In a double-blind trial involving acutely manic patients, clonazepam was compared to placebo, both groups receiving chlorpromazine as needed. The group receiving clonazepam showed significantly more improvement in their manic but not their psychotic symptoms compared to the placebo group. This effect was not primarily related to the sedative effects of clonazepam. Clonazepam tended to reduce the need for phenothiazine medication. Side effects related to sedation were more common to the clonazepam group. These findings are the first to indicate that clonazepam may have a specific antimanic effect over and above that of phenothiazines alone. PMID- 1877959 TI - Attitudes of psychiatric patients and their relatives to involuntary treatment. AB - In 1979 a Guardianship Board assumed responsibility in South Australia for the welfare of those mentally ill or handicapped people unable to look after their own health or safety, or to manage their own affairs. This study examines the attitudes to guardianship and involuntary treatment of 79 patients referred to the Board from a psychiatric hospital, all of whom were under guardianship at the time of the study. Forty-seven of their relatives took part in the project, which included measures of patients' psychiatric symptoms and relatives' punitiveness. Although almost 70% of patients objected to Guardianship in principle, they made more positive than negative statements about it. Nearly 60% rated involuntary treatment, including medication, as helpful. Patients reported a level of psychiatric symptoms less than half of that of a psychiatric outpatient sample. Relatives were strongly in favour of Guardianship, stating frequently that it allowed an improved relationship between themselves and the patient. Patients who believed that they were suffering from a mental illness were comparatively happy about being under Guardianship, and a belief that the patient was mentally ill was significantly associated with reduced extrapunitiveness in relatives. PMID- 1877961 TI - Concordance with recommendations in a consultation-liaison psychiatry service. AB - We studied the concordance of physicians with the recommendations of psychiatric consultants in a sample of 270 consultations in a 400-bed general hospital. Of the patients about whom a consultation was sought, 37% had a past psychiatric history, and 67% were on psychotropic drugs. Twelve percent had Organic Mental Disorder, 35% Affective Disorder, and for 24% no DSM-III diagnosis could be made. The psychiatrist made psychotropic drug recommendations in 62%, and the physicians' concordance with this recommendation was 86%. The physician's discharge summary included a diagnosis which concorded with the psychiatrist's diagnosis in 53% of files. The psychiatrist recommended further investigations in only 5.2% of files. PMID- 1877962 TI - Propofol as an anaesthetic agent for ECT: effect on outcome and length of course. AB - Recent reports of reduced seizure duration with ECT under propofol anaesthesia have led to concerns that propofol may diminish the efficacy of this treatment. To investigate the effect of propofol on the response to ECT, we reviewed records of 66 patients with primary depression treated with ECT, 37 of whom had been assessed prospectively with pre- and post-ECT Hamilton and Zung depression severity ratings. Despite demonstrating that the individual seizure duration was significantly reduced with propofol compared to thiopentone we found no evidence of reduced ECT efficacy with propofol. Courses under propofol anaesthesia were on an average two treatments longer than with thiopentone. Although this difference was not statistically significant this may have been due to a type II error. These results suggest that it is premature to abandon the use of this new anaesthetic agent in ECT without controlled prospective outcome studies. PMID- 1877963 TI - Authoritarianism among medicine and law students. AB - This study assessed the effects of gender, faculty, and year (level) on "authoritarianism" among university students within the faculties of law and medicine. A questionnaire, using the Ray Adapted F Scale to measure authoritarianism, was administered to 454 students at the University of Western Australia. The first, third and sixth year medical students were compared with first, third and final year law students. Gender alone was responsible for a significant source of variance, with males more authoritarian than females. Faculty alone showed a strong trend towards significance with medicine more authoritarian than law. Although no other 2- or 3- way interactions were significant a trend was apparent in which females became more and males less authoritarian with increasing level. PMID- 1877964 TI - A 13 year follow-up of child psychiatry training. AB - The graduates from two child psychiatry training programmes over a 13 year period responded to a questionnaire designed to elicit their retrospective evaluations of various aspects of their educational experience. Information is presented about areas of knowledge judged important, specific experiences which were helpful and unhelpful, and current patterns of practice of these graduates. Their attitudes toward supervision and supervisors are discussed, as are implications for recruitment of future trainees and teachers/faculty. PMID- 1877965 TI - The self-organization of human psychological functioning. AB - This article describes the traditional model of human psychological functioning which dominates current theorizing, contrasts it with the new, emerging perspective of self-organizing processes, and applies this new approach to a theory of human psychological functioning. In the traditional model there is an assumption that processes of functioning are discretely different from physical structure. This assumption is shown to be intrinsic to a linear conceptual framework which implies that (a) stability of functioning derives from physical structure; (b) functioning is determined by the effects of enduring, antecedent components; (c) the environment can selectively influence structure; and (d) observational methods are capable of accessing and revealing processes of functioning. In the contrasting self-organizational perspective, structure and functioning are assumed to be given in one another at the level of organizational process. This formulation implies that as a system functions (a) its orderliness and stability are being determined by the ongoing functioning itself; (b) at the level or organizational functioning there are no antecedent structures separate from consequent activity; (c) systemic functioning exists as a unitary and continuous organizational process; and (d) organizational functioning cannot be instructed by environmental events. The work of Prigogine and of Maturana are examined as a basis for a theory of human psychological functioning as a self organizing system. The theory that is proposed describes how attentional and experiential functioning evolve as a system of organizational continuity and coherence and how the process by which people recognize and identify their functioning secures this organizational functioning. PMID- 1877966 TI - Beneficial effects of bradykinin on porcine ischemic myocardium. AB - Exogenous bradykinin was administered to pigs in which an experimental infarction was evoked by ischemia and reperfusion. Ischemia (45 min) was induced in a closed chest model with a balloon catheter in the left anterior descending artery, reperfusion by deflating and removing the balloon. The pigs were treated with saline (n = 11) or bradykinin (0.1 mg/kg in 30 min) infusion (n = 10) during the last 15 min of the ischemic period and the first 15 min of reperfusion. During ischemia, heart rate increased in the saline group to 120 +/- 9% of the initial value (p less than 0.05) and in the bradykinin group to 155 +/- 13% (p less than 0.05). After reperfusion, the rate-pressure product was increased in both groups. The increase of arterial creatine kinase levels was significantly less in the bradykinin-treated group. However, the catecholamine and purine levels were increased, as was the plasma renin activity when compared with the saline group. Two weeks after the infarction, six pigs had died in each group. In three out of five surviving saline-treated pigs and one out of four surviving bradykinin treated pigs, a sustained ventricular tachyarrhythmia was inducible after programmed electrical stimulation. In conclusion, although systemically administered bradykinin caused a temporary increase in myocardial ischemia, it did reduce the (enzymatic indices of) infarct size. Therefore, the beneficial effects, previously found for ACE-inhibitors might at least partially be related to the potentiation of endogenous bradykinin. PMID- 1877968 TI - Coronary artery anomalies and bicuspid aortic valves in the Syrian hamster. AB - The condition of coronary arteries and aortic valves was studied in 552 Syrian hamsters belonging to a single family subjected to high endogamous pressure. The study was carried out using a corrosion-cast technique. In 178 hamsters the aortic valve was bicuspid. In 138 specimens, 54 of them with normal aortic valves and 84 with bicuspid aortic valves, anomalies in the origin of the coronary arteries could be classified in three morphologic types: left coronary artery from the pulmonary trunk (36 cases); single right coronary artery (84 cases); left coronary artery from the dorsal aortic sinus (18 cases). Results of a chi 2 contingency test show that the frequency of left coronary artery from the pulmonary trunk and single right coronary artery significantly increases when the aortic valve is bicuspid. The present findings suggest that there is a developmental complex consisting of biscuspid aortic valve and anomalous origin of the coronary arteries. PMID- 1877967 TI - Lack of significant effects of superoxide dismutase and catalase on development of reperfusion arrhythmias. AB - It has been reported that agents having the ability to scavenge oxygen-derived free radicals reduce the severity of ventricular arrhythmias that occur after brief coronary occlusion and reperfusion. Superoxide dismutase plus catalase (SOD + CAT) or placebo was administered in a blinded randomized fashion prior to coronary occlusion in rats (n = 25 each group) undergoing a 5-min left coronary occlusion followed by 15 min of reperfusion. During reperfusion, ventricular tachycardia (VT) developed in 96% of animals in both groups. Reperfusion ventricular fibrillation (VF) developed in 60% of the placebo group vs 56% in the SOD + CAT group (p = 1.0). Irreversible VF occurred in 40% of the placebo group vs 20% in the SOD + CAT group (p = 0.22). Atrioventricular block occurred in 12% of placebo and 4% of SOD + CAT animals (p = 0.61). There were no significant difference between groups in duration of VT (85 +/- 15 s (mean +/- SEM) placebo vs 81 +/- 14 s SOD + CAT, p = 0.81), total duration of VT plus VF (391 +/- 76 s placebo vs 256 +/- 64 SOD + CAT, p = 0.45) or numbers of single ventricular ectopic beats (65 +/- 15 placebo vs 97 +/- 18 SOD + CAT, p = 0.18). Heart rate at reperfusion was slightly higher in control than SOD + CAT animals (340 +/- 33 vs 319 +/- 32, p = 0.02). Risk zone size, determined by Monastral blue injection, was equal in both groups (34 +/- 2% of ventricular mass). The occurrence of reperfusion VF in this model could not be predicted by heart rate at reperfusion (331 +/- 33 VF animlas vs 328 +/- 36 no VF, p = 0.77), or by risk zone size (34 +/- 2%, VF and no VF groups).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1877969 TI - The interaction of the Bainbridge and Bezold-Jarisch reflexes in the conscious dog. AB - Experiments were undertaken to determine the efferent path of the Bainbridge reflex and to investigate the interaction of the Bainbridge reflex with the Bezold-Jarisch reflex in conscious, chronically instrumented dogs. The Bainbridge reflex was elicited by distending the left atrium by inflating a chronically implanted balloon catheter. The Bezold-Jarisch reflex was elicited using chemical stimulation of left ventricular receptors with infusions of veratridine (0.1-0.8 micrograms/kg/min) into the left circumflex coronary artery. Heart-rate responses to left atrial balloon inflation were compared before and after either beta-1 antagonism with metoprolol or cholinergic antagonism with atropine, and before and during left ventricular receptor stimulation with intracoronary veratridine. Left atrial balloon inflation alone caused a significant increase in heart rate (70.1 +/- 5 bpm), left atrial pressure (14 +/- 3 mmHg) and mean arterial blood pressure (10 +/- mmHg). Heart-rate responses to left atrial distension were inhibited, but not abolished by either cholinergic or beta-1 antagonism. Left atrial distension after both cholinergic and beta-1 antagonism abolished the heart-rate response to balloon inflation. These results indicate that the efferent component of the Bainbridge reflex has both a vagal and a sympathetic component in conscious dogs. Left atrial distension during simultaneous left ventricular receptor stimulation resulted in a significantly decreased tachycardia than did left atrial distension alone (26 +/- 3 bpm compared to 68 +/ 8 bpm in the control experiments). In addition, the slope of the heart rate vs left atrial pressure relationship was significantly inhibited by left ventricular receptor stimulation (1.8 +/- 0.2 bpm/mmHg compared to 5.7 +/- 0.3 bpm/mm Hg in the control experiments). There were no significant differences in either the left atrial pressure or arterial blood pressure changes between the two groups. These data suggest an interaction between these two reflexes that may be occurring in the central nervous system. PMID- 1877970 TI - Significance of geometrical reference models of the left ventricle for a new concept of evaluation of cardiac pumping function. AB - A methodological approach based on Frank's pressure-volume (P-V) diagram and model calculations for analyzing the determinants of stroke volume (SV) under conditions of altered ventricular geometrical configuration is discussed with respect to the underlying geometrical models. The approach is generalized in the sense that alterations in myocardial elasticity are considered. In addition, simplifying assumptions on which the stress-length (sigma-1) diagram in previous studies was based are now discarded. It can be shown that calculated stroke volume is only slightly affected by the choice of the models when referring to average wall stress. However, if we use the formula for midwall stress recommended by Mirsky, then the influence of the geometrical model becomes more important. Based on the example of a rat with experimental aortic stenosis in the decompensated stage it is demonstrated that this methodological approach is an indispensible completion of O. Frank's concept when evaluating ventricular dynamics, and could gain clinical significance in future. PMID- 1877971 TI - Cell culture systems to study progression and inhibition of intimal proliferations. AB - Vascular smooth muscle cells, endothelial cells, and fibroblasts are the main cellular constituents of artery walls. Mass cultures and clone cultures of these cell types have meanwhile become valuable tools in the research of the genesis, pathophysiology, and therapy of vessel-wall diseases. With transfilter co-culture systems the three-layered construction of the artery wall can be imitated in vitro, and it has become possible to induce smooth muscle cell proliferates in these in vitro system which resemble, in many respects, intimal proliferates as they often occur after angioplasty, stent- or bypass operations in the form of secondary stenoses. With this technique the interaction of the three cell species of artery walls can be easily studied. The time-course of the development of smooth muscle cell proliferates in vitro resembles the in vivo scenario. Addition of oxidized lipoproteins and monocytes to the culture medium of transfilter cultures leads to atheroma-like proliferates. Culturing whole artery segments is another in vitro technique for induction of intimal proliferates, and enables the production of intimal proliferates in a way similar to transfilter culture systems. Because of the striking similarities of the cellular responses of transfilter- and organ-culture systems with in vivo processes in atherogenesis, and in the development of secondary stenoses after angioplasty, the described co culture systems are suitable for studying the genesis, pathophysiology, and therapy of stenosing artery processes, as well as to obtain further insight into basic problems of cell interaction in vessel walls. PMID- 1877973 TI - S'-subsite mapping of endoproteinase Glu/Asp-C from Actinomyces sp. AB - The S'-subsite specificity of the endoproteinase Glu/Asp-C from Actinomyces sp. was studied by acyl transfer reactions using amino-acid- and peptide-derived nucleophilic amino components. The following results were obtained: 1. The enzyme prefers amino acid amides with hydrophobic side chains in P'i position. In addition, positively charged functions in this position favour S'-P' interactions significantly. 2. Stereospecific binding is a prerequisite for nucleophilic efficiency. 3. Dipeptide amides are more efficient amino components in comparison to free dipeptides whereas oligoglycines show a poor nucleophilic behaviour independent of chain length. PMID- 1877972 TI - Adaptive protection of the heart and stabilization of myocardial structures. AB - Adaptation of animals to short-term stress exposure (ASE) protected the heart against arrhythmias in acute ischemia and reperfusion and eliminated the decrease in threshold of fibrillation and arrhythmias is acute myocardial infarction and postinfarction cardiosclerosis. Cardioprotective effect of ASE was provided not only by the activation of GABAergic, opioidergic and cholinergic stress-limiting system but also by a mechanism formed at the level of heart itself. Isolated hearts of animals adapted to short-term stress exposure possessed a strikingly enhanced resistance to toxic doses of catecholamines, Ca2+, and to reperfusion damage following total ischemia. Contracture-inducing and arrhythmogenic effects of these factors and the release of CK into the perfusate were manifold reduced in ASE. Mitochondria and elements of SR Ca-pump isolated from the hearts of adapted animals were much more resistant to autolysis. This phenomenon of adaptive stabilization of structures (PhASS) was accompanied by the accumulation of HSP 71 and a simultaneous increase in the heart thermal stability. In the coronary artery ligation the PhASS lacked the anti-ischemic effect, but it provided a decrease of the necrotic zone by more than 40%, the ischemic zone being unchanged, due to its cytoprotective effect. PMID- 1877974 TI - Determination of osteocalcin in serum by an ultramicro-ELISA with alkaline phosphatase as marker enzyme. AB - A competitive ELISA for osteocalcin in 10 microliters samples has been developed with alkaline phosphatase as a marker enzyme. The assay for osteocalcin has an inter-assay and intra-assay variability of 13% and 12%, respectively; the limit of detection is 3.6 pg per assay. The assay was used to measure osteocalcin serum levels in patients with chronic hemodialysis and several bone diseases. The method for the purification of osteocalcin is also described. PMID- 1877975 TI - Preparation of a neoglycoprotein using a homobifunctional reagent and its applicability for protein blotting and electron microscopy. AB - A new method for the preparation of a neoglycoprotein (chemically mannosylated bovine serum albumin, D-Man.BSA) is described using the homobifunctional reagent divinylsulphone.D-Man.BSA purified by affinity chromatography on ConA-Sepharose 4B shows microheterogeneity as demonstrated by immunoaffinity electrophoresis with free ConA in the first-dimension gel. The dissociation constant K for the neoglycoprotein-ConA complex has been calculated to be 2.5.10(-5) M. Biotinylated D-Man.BSA is a useful reagent to detect carbohydrate binding proteins of L1210 leukemia cells on blots. The neoglycoprotein labelled with colloidal gold may be used to demonstrate L1210 cell surface D-Man binding proteins by preembedding electron microscopy. PMID- 1877976 TI - Influence of white blood cells on the filterability of human erythrocytes: modelling of the filtration process and experimental results. AB - In medical research and clinical practice, the increasing application of filtration measurements, to characterize the erythrocyte deformability has aroused an intensive discussion about possible erroneous interpretations of measured values (filterability indices). In the present paper the influence of white blood cells (WBC) on these indices is described and discussed in relation to a mathematical model of the filtration process. We found for two gravity filtration systems, using cellulose filters and concentrated erythrocytes suspensions sensitivities of their filterability indices of (1 +/- 0.1)% per 100 WBC/microliter (initial filtration rate measurement) and (3 +/- 0.3)% per 100 WBC/microliter (hemofiltrometer). In comparison to Nuclepore filtration systems with sensitivities of 5-12% per 100 WBC/microliters, cellulose filters were much less sensitive to WBC. The necessity, advantages and disadvantages of additional procedures for WBC removal are discussed. A standardization of residual WBC-count in limits of 500 +/- 300 WBC/microliters at a hematocrit of 60% is proposed. Fitting of the filtration curves of the hemofiltrometer to a model function may either improve the accuracy of estimation of filterability indices or divide them into two model parameters with different WBC-sensitivities: the initial filtration rate parameter having a low WBC-sensitivity ((0.9 +/- 0.2)% per 100 WBC/microliter) and the occlusion related parameter having a 12 times higher sensitivity ((11 +/- 1)% per 100 WBC/microliter). Interpretation, advantages and disadvantages of the model parameters are discussed also in comparison to the filterability index. PMID- 1877977 TI - Disturbance of brightness discrimination and active avoidance learning after lesions of nucleus reticularis tegmenti pontis (NRTP) of rats are related to impairment of goal-directed behaviour. AB - Long-Evans hooded rats were not able neither to reach criterion of active avoidance tasks in a Y-maze and in a jump test, nor in brightness discrimination after lesions of the NRTP without preoperative experience in these tests. After preoperative consolidation of active avoidance, the retention of Y-maze avoidance performance was zero and of jump test avoidance at 25%. The Y-maze avoidance was again relearned except in the task with 2:2 alternation of goals whereas retention of brightness discrimination was not affected. In the jump test, avoidance relearning was evidently retarded. Ambulatory and exploratory behaviour in the open field were significantly reduced after NRTP lesions. The NRTP is evidently involved in the establishment and control of goal-directed behaviour. PMID- 1877978 TI - Natriuresis secondary to carotid chemoreceptor stimulation with almitrine bismesylate in the rat: the effect on kidney function and the response to renal denervation and deficiency of antidiuretic hormone. AB - Almitrine bismesylate simulates the effects of arterial hypoxia in producing a specific and long-lasting excitation of the peripheral arterial chemoreceptors. Previous work has shown that almitrine produces a diuresis and natriuresis when given intravenously to anaesthetised rats in a stable mannitol induced diuresis. This response is abolished by glossopharyngeal nerve section implying that it is afferently mediated via the carotid body chemoreceptors. We have studied further the efferent limb of this response. The diuresis and natriuresis occurs without significant detectable changes in effective renal plasma flow and glomerular filtration rate suggesting that it is produced mainly by inhibition of renal tubular sodium and water reabsorption. Almitrine produces a diuresis and natriuresis in rats after bilateral nephrectomy and transplantation of a kidney from a donor rat. This effect is not therefore efferently mediated by the renal nerves and probably involves a humoral agent. Almitrine produces a diuresis and natriuresis in rats after bilateral adrenalectomy and in rats with congenital hypothalamic diabetes insipidus indicating that neither adrenal hormones nor changes in antidiuretic hormone levels are implicated. PMID- 1877979 TI - Pharmacokinetics of almitrine in healthy volunteers and patients with essential hypertension. AB - Pharmacokinetic studies with the arterial chemoreceptor stimulant almitrine (100 mg per os) were performed in 12 healthy volunteers and 8 patients with essential hypertension stage I in order to evaluate the suitability of the drug for physiological tests. The parent compound was determined gas-chromatographically. Almitrine was absorbed with maximal serum levels after 1.8 +/- 0.4 h in healthy volunteers and 1.5 +/- 0.3 h in patients. The elimination proceeded biexponentially with terminal half-lives from 14.6 to 43.4 h in volunteers and 12.5-45.0 h in patients. Further characteristics were large distribution volumes (16.1 +/- 4.5 ml/g in healthy volunteers, 13.9 +/- 4.7 ml/g in patients) and large interindividual variations of all pharmacokinetic parameters by a factor of 2 to 6. Significant differences between healthy individuals and patients were not observed. The drug was well tolerated. The pharmacokinetic properties of almitrine should be included into its evaluation as a test compound. PMID- 1877980 TI - Incisor growth acceleration after lesions in the lateral pontine reticular formation of rats. AB - The length of upper and lower incisors of Long-Evans hooded rats between gingiva and top were measured before and after small bilateral symmetric electrolytic lesions of the pontine reticular formation between the ventromedial parabrachial nucleus and the motor trigeminal nucleus. Ten days after lesions of this region 8.5 mm posterior to bregma the length of upper incisors was 13.4 +/- 0.7 mm compared with 6.1 +/- 0.2 mm before lesion (p less than 0.01) and the length of the lower incisors 17.1 +/- 0.4 mm compared with 10.2 +/- 0.2 mm before lesion (p less than 0.01). A second group with a smaller lesion of this region 9.0 mm posterior to bregma reached upper incisor length of 13.2 +/- 0.4 mm (p less than 0.05) and lower incisor length of 14.7 +/- 0.5 mm (p less than 0.05) at the 20th postoperative day. Sham-operated controls had no tooth growth acceleration. PMID- 1877981 TI - Mitochondrial pyruvate dehydrogenase complex subunits as autoantigens in human primary biliary cirrhosis. AB - Primary biliary cirrhosis is an evolutive and chronic human liver disease characterized by presence of antimitochondrial autoantibodies in the serum. We present the biochemical definition of these autoantigens and show that purified pyruvate dehydrogenase complex contains three of the major mitochondrial antigens of M2 type i.e. the E2 subunit (dihydrolipoamide acetyl transferase), the X subunit and the E1 alpha subunit (pyruvate dehydrogenase), by immunoblotting experiments and inhibition of enzyme activity with several types of serums. PMID- 1877982 TI - Phosphamidon, methylparathion and dichlorvos impact on tissue oxidative metabolism in penaeid prawn, Metapenaeus monoceros. AB - Changes in oxidative metabolism of hepatopancreas and muscle tissues of penaeid prawn, Metapenaeus monoceros was studied, following its exposure to selected organophosphorous insecticides phosphamidon, dichlorovos and methylparathion. The OPI are found to inhibit the activity levels of acetylcholinesterase, succinate dehydrogenase, isocitrate dehydrogenase, pyruvate dehydrogenase, lactate dehydrogenase and cytochrome-c-oxidase and cause accumulation of acetylcholine in the hepatopancreas and muscle tissues. These changes in the activity levels of selected oxidative enzymes during insecticide exposure in these tissues of prawn indicates the shift in the metabolic emphasis from aerobic to anaerobic conditions and is interpreted as a functional adaptation to insecticide induced metabolic stress. These observed changes at cellular level pave way for successful survival of prawns in insecticide polluted environ. PMID- 1877983 TI - Purification and characterization of the glycoprotein allergen from Prosopis juliflora pollen. AB - Highly active glycoprotein allergens have been isolated from pollen of Prosopis juliflora by a combination of Sephadex G-100 gel filtration and Sodium dodecyl sulphate-Poly-acrylamide gel electrophoresis. The glycoprotein fraction was homogeneous, and had molecular weight 20,000. The purified glycoprotein allergen contained 20% carbohydrate, mainly arabinose and galactose. Enzymatic digestion of glycoprotein with protease released glycopeptides of molecular weight ranging from less than 1,000 to more than 5,000 on Sephadex G-25 gel filtration. Antigenicity or allergenicity testing of these glycopeptides by immunodiffusion, immunoelectrophoresis, and radioallergosorbent test indicated complete loss of allergenic activity after digestion with protease whereas incubation with beta-D galactosidase and periodate oxidation had little affect on the allergenic activity of the glycoprotein fraction. But incubation with alpha-D-glucosidase did not affect the allergenic activity significantly. All these tests indicated that protein played significant role in allergenicity of P. juliflora pollen. PMID- 1877984 TI - Insulin mimetic role of vanadate on plasma membrane insulin-receptors. AB - Vanadate possesses insulin-mimetic effects, and has been reported to correct the metabolic imbalances in streptozotocin-induced diabetes. Rats were made diabetic by a single i.v. injection of streptozotocin (55 mg/kg body weight) in citrate buffer. After the onset of diabetes, the diabetic rats were treated with sodium orthovanadate (0.3 mg/ml) for 15 days. The increased percentage of 125 I insulin binding to the liver plasma membrane insulin receptors and increased plasma membrane phospholipids were found to be reduced significantly in vanadate treated diabetes. Hence the mode of action of vanadate may be similar to that insulin. PMID- 1877985 TI - B--Z conformational transition in d(CGCGCGTTAATT), d(CGCGCGTTAA) and d(CGCGCGTT). AB - Conformational studies on three DNA-oligomers (d(CGCGCGTTAATT), d(CGCGTTAA) and d(CGCGCGTT) in solution by circular dichroism spectroscopy are reported. In low salt solution, all three DNA oligomers exhibit a characteristic B-conformation. However, under the influence of high salt concentration i.e. 5M NaCl, the octamer d(CGCGCGTT) exhibits 'A' conformation whereas the decamer and dodecamer retain B conformation. On addition of millimolar amount of NiCl2 to the 5M NaCl, solution of oligodeoxynucleotides a B-Z transition is observed in octamer, decamer and dodecamer. However, NiCl2 titrations show that mid point of transition for dodecamer is at 2.25 mM, for decamer is at 13 mM NiCl2 and for octamer is 17 mM at NiCl2. In 60% alcohol all three oligonucleotides remain in the B-conformation. The melting temperatures of oligonucleotides at various salt concentration are also reported. Thermodynamic parameters calculated by melting profile using a two state model show that dodecamer and decamer are most stable in their 5M NaCl, B form. However, octamer is more stable in its Z form than that of its 'A' form. PMID- 1877986 TI - Fenvalerate induced changes in evoked potentials from the ventral nerve cord (VNC) of cockroach, Periplaneta americana. AB - Changes in evoked potentials from the VNC of P. americana were recorded under in vitro and topical application of sublethal doses of fenvalerate. In this study significant changes in physical characteristics of action potentials like threshold voltage, duration, latency and amplitude were noticed. In in vitro studies the effects were found to be dose dependent, while in topical exposure maximum effect was noticed at 3h, followed by recovery during subsequent periods of exposure. Moreover, changes were more pronounced in in vitro than topical exposure. PMID- 1877987 TI - Characterization of a hexammineruthenium-stimulated external NADH oxidase from rat liver mitochondria. AB - The existence of an external hexammineruthenium-stimulated NADH oxidase in rat liver mitochondria is postulated. This enzyme is localized on the outer surface of the inner mitochondrial membrane, is specific for NADH and requires oxygen. The apparent affinity of the enzyme for NADH amounts to about 4 microM. Furthermore, the enzyme is characterized by an alkaline pH optimum and a linear Arrhenius plot (14 kJ/mol). The electron transfer from NADH to oxygen is not linked with the respiratory chain but is connected with the formation of superoxide radicals. PMID- 1877988 TI - Cultured bovine endothelial cells convert big endothelin isopeptides to mature endothelin isopeptides. AB - The incubation of big endothelin-1 (big ET-1), big ET-2 or big ET-3 with cultured bovine endothelial cells (ECs) resulted in their conversions to mature endothelins (ETs). These conversions apparently exhibited Michaelis-Menten kinetics as a function of each big ET isopeptide. The conversions of big ETs were abolished by phosphoramidon. These results indicate that vascular endothelium can convert exogenous big ET-1 to mature ET-1 through a phosphoramidon-sensitive metalloprotease, and that this enzyme has also high affinities for big ET-2 and big ET-3. PMID- 1877989 TI - Subacute physiological stress induced by phosphamidon on carbohydrate metabolism in midgut gland of prawn, Penaeus indicus. AB - Midgut gland carbohydrate metabolism of penaeid prawn, Penaeus indicus was studied on acute and acclimation to sublethal concentration of phosphamidon. The midgut gland tissue of acclimated prawn showed inhibited glycolysis with an onset of gluconeogenesis. In general acclimation to sublethal concentration resulted in the elevation of the synthetic phase of midgut gland carbohydrate metabolism. PMID- 1877990 TI - Charge forms of serum and whey transferrin in rat differ in the sialic acid content of their glycan chains: immunological implications. AB - Transferrin has been purified from both rat whey and rat serum. Both proteins migrated as the same size on electrophoresis in the presence of sodium dodecyl sulphate but when electrophoresed under native conditions showed the presence of multiple charge forms. The patterns observed were not altered by iron binding or removal and all forms were shown to bind iron. Treatment with neuraminidase tended to condense all bands into a single species common to both transferrins whereas treatment with a peptide N-glycosidase resulted in a complex pattern of bands consistent with removal of one of the two glycan chains of the transferrins. A sensitive enzyme-linked immunosorbent assay (ELISA) was set up to examine the transferrins. Iron binding and removal and treatment with peptide N glycosidase all modified the ELISA signal obtained. Neuraminidase, however, did not affect the ELISA signal. PMID- 1877991 TI - Effect of polyunsaturated (PUFA n-6) and saturated fatty acids-rich diets on macrophage metabolism and function. AB - Previous reports of our laboratory have shown that PUFA (n-6)-rich diets cause important changes of the metabolism of the immune tissues. In this study, alterations of macrophage metabolism and function were examined in rats fed polyunsaturated (UC) or saturated (SC) fatty acids-rich diets during 6 weeks. The UC group decreased intraperitoneal cell migration and macrophage phagocytosis. These changes were related to modifications of macrophage metabolism. The UC group showed also increased G-6-PDh in inflammatory macrophages. These findings suggest that pentose-phosphate pathway is not the unique metabolic factor to control phagocytosis. PUFA-rich diet reduced glutaminase activity. Therefore, this amino acid might be one of the possible metabolic reasons for the impaired macrophage function observed. PMID- 1877992 TI - Influence of antioxidants on SOD activity in bovine sperm. AB - SOD activity and susceptibility to peroxidation on spermatozoa from frozen and fresh bovine semen were determined either in presence or not of synthetic (BHA) or natural (vitamin E) antioxidants. In sperm suspensions incubated with vitamin E, SOD activity was higher than in the control samples and the ones treated with BHA. It was found a highly significative correlation between malondialdehyde production and SOD activity. SOD activity could be used in bovine spermatozoa as a metabolic indicator of membrane integrity. PMID- 1877993 TI - Altered [3H]ryanodine binding is not associated with malignant hyperthermia susceptibility in terminal cisternae preparations from swine. AB - Based on comparisons between Pietrain malignant hyperthermia susceptible swine and Yorkshire control swine, other investigators have reported a 3-fold lower Kd for [3H]ryanodine binding to terminal cisternae in the malignant hyperthermia swine. However, the Kd of [3H]ryanodine binding did not correlate with malignant hyperthermia susceptibility when examined within the same strain (a Yorkshire/Duroc cross) in the present study. The values of Kd for the malignant hyperthermia susceptible and control swine in the present study were similar to those previously reported for the Pietrain strain, suggesting that the control strain chosen, not malignant hyperthermia susceptibility, accounts for what appeared to be a low Kd in Pietrain muscle. PMID- 1877994 TI - Some biochemical properties of human lymphoblastoid Namalwa cells grown anaerobically. AB - Using cultured lymphoblastoid Namalwa cells, we have demonstrated that humans cells can be grown for long periods in the absence of oxygen. Such anaerobic growth occurs at the same rate as that of aerobic cultures, but is characterized by a strict dependence on pyruvate. Cells in anaerobic culture undergo a severe loss of mitochondrial cytochromes, that is reversible on reaeration. Anaerobically grown cells show a two-fold increase in glucose consumption, consistent with anaerobic glycolysis providing the source of ATP for cellular maintenance and growth. The requirement for pyruvate is explained by the necessity for these cells to re-oxidise NADH derived from metabolic reactions. Detailed study of anaerobically grown human cells provides a new framework for investigating tissues depleted in mitochondrial functions, as occurs in mitochondrial diseases and the ageing process. PMID- 1877995 TI - Studies on the changes in plasma lipids and lipoproteins in patients with benign and malignant breast cancer. AB - Experimental studies and epidemiological data suggest that, high fat diet increases the risk of developing breast cancer, both in animal and in human population. Cases of postmenopausal, untreated women with malignant and benign breast tumors, were compared for their age, body weight, plasma lipid fractions and lipoproteins. There was a significant increase in body weight, total plasma lipids, total cholesterol, LDL--cholesterol, VLDL--cholesterol, phospholipids, triacylglycerols, free fatty acids in malignant breast cancer patients. HDL- cholesterol had been significantly decreased in benign and malignant patients when compared with the control subjects. PMID- 1877996 TI - Effect of atrazine on some aspects of lipid metabolism in fresh water fish. AB - The impact of atrazine, a triazine herbicide, on the lipid metabolism of fish, Sarotherodon mossambica was studied. Significant changes were reported in the lipid profiles of liver and muscle as a function of exposure period. PMID- 1877997 TI - Alteration of the ecto-protein phosphorylation profile of intact goat spermatozoa during epididymal maturation. AB - Intact cauda-epididymal mature and caput-epididymal immature goat spermatozoa were assessed for their capacity to phosphorylate the outer surface proteins upon incubation in a modified Ringer's solution containing [delta-32P]ATP. The immature spermatozoa possessed markedly greater (approximately 7-fold) efficacy to phosphorylate the ecto-proteins than the mature cells. Autoradiographic analysis of the 32P-labelled proteins resolved by SDS-PAGE, showed that multiple sperm ecto-proteins are phosphorylated by an endogenous ecto-cyclic AMP independent protein kinase (CIK) and the phosphorylation profile of these proteins underwent marked alteration during the epididymal sperm maturation. The intact caput-sperm as well showed nearly 4-fold higher specific activity of ecto CIK than the cauda-sperm when the kinase activity was estimated using phosvitin as the exogenous protein substrate. The data suggest that the ecto-CIK and its specific protein substrates located on the sperm outer-surface, may have important roles in regulating the epididymal maturation of the male gametes. PMID- 1877998 TI - We are part of the planet, you know! PMID- 1877999 TI - Risk management. Turning liabilities into manageable responsibilities. PMID- 1878000 TI - May you live with "interesting" laws. Government regulation in the 1990s. PMID- 1878001 TI - Sign language. PMID- 1878002 TI - The consultive model with computers. An innovation in service delivery. AB - As the field of communication disorders continues to evolve, it must look beyond itself to bring together all the resources available in a community to maximize the process of remediation. The consultive model effectively does this by extending the amount of stimulation and feedback available to the client. The addition of the computer to the process provides a structure for agents of change that can be controlled by the supervising clinician. The computer also enhances accountability and improves report-generation capabilities. Although there are still many factors to consider, the consultive model using computers promises to be an efficient, effective service delivery system for the treatment of communication disorders. PMID- 1878003 TI - Adults with neurological impairment from multicultural populations. Results of a clinical survey. PMID- 1878004 TI - A profile of clinical coordinators in ESB-accredited training programs. PMID- 1878005 TI - Characterization of the fluorescent morphological structures in human arterial wall using ultraviolet-excited microspectrofluorimetry. AB - In this study, the fluorescent morphological structures in normal coronary artery, normal aorta, and atherosclerotic aorta were histochemically identified and spectroscopically characterized in situ using ultraviolet-excited microspectrofluorimetry. Excitation wavelengths of 290 nm and 310/312 nm were employed to observe two distinct fluorescence bands, with peak emission wavelengths near 335 nm and 380 nm, respectively. Emission of the short wavelength 335 nm band, previously assigned to tryptophan residues in tryptophan containing proteins, was observed from all the morphological structures in the vessel walls and was isolated in groups of smooth muscle cells in aorta and coronary artery media. The long wavelength 380 nm band was assigned to distinct fluorophores associated with the structural proteins collagen and elastin and was observed in collagen fibers and elastic fibers, respectively. The corresponding morphological structures in normal aorta, normal coronary artery, and atherosclerotic aorta exhibited similar fluorescence lineshapes. In atherosclerotic plaque, a distinct fluorescence band, peaking near 370 nm, was observed in the emission from both ceroid granules and necrotic core. Using a simple, quantitative model, differing contributions of collagen, elastin, and tryptophan-containing protein fluorescence were shown to account for over 95% of the emission from the intima, media, and adventitia layers of non-necrotic aorta and coronary artery. PMID- 1878006 TI - Apolipoprotein E deficiency with a depressed mRNA of normal size. AB - We studied a 39-year-old man who had palmar xanthomas complicated with marked hyperlipidemia. His serum cholesterol and triglyceride were 2000 and 6300 mg/dl, respectively. Serum apolipoprotein E (apo E) was undetectable in the patient by the methods of single radial immunodiffusion, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and radioimmunoassay. Serum apo E concentrations of his father and sister were low. This evidence is consistent with a diagnosis of familial apo E deficiency. We studied the synthesis of apo E in cultures of peripheral blood monocyte macrophages (M-M cultures) obtained from the patient, and detected no secretion of apo E in the culture medium and no newly synthesized apo E in the cell lysate. There were only trace amounts of apo E mRNA of the M-M cultures and the size of the mRNA appeared the same as normal apo E mRNA, indicating a different mutation of the gene from that of the case reported by Zannis et al. (J. Biol. Chem., 260 (1985) 12891). PMID- 1878007 TI - Hemorheological disturbances, metabolic parameters and blood pressure in different types of obesity. AB - Body fat distribution characterized by a high waist/hip ratio (WHR) has been described as a risk factor in the incidence of cardiovascular diseases and associated mortality. Hemorheological changes have been shown to accompany several risk factors. Gynoid and android obese women were compared in the present study with respect to hemorheological and metabolic variables and blood pressure. The android obese women had a significantly higher hematocrit and red blood cell count and showed higher blood viscosity at both high and low shear rates than women with the gynoid obesity type. Blood pressure was also higher in the android group. No significant differences were shown in concentration of cholesterol or triglycerides in serum nor in the microrheological properties of the red blood cells. The filterability index, which mirrors the number of rigid erythrocytes in the blood, was found to correlate with the plasma insulin concentration (r = 0.78, P less than 0.05) in the android but not in the gynoid obese women. It is concluded that the pathological changes in blood rheology observed in the android obese women may contribute to the high rate of cardiovascular events and associated mortality reported in this type of obesity. PMID- 1878008 TI - Hyperlipoproteinemia in one-year-old analbuminemic rats. AB - Plasma lipoprotein distribution and apolipoprotein concentrations, as well as kidney function and histopathology of heart, aorta, liver and kidney were investigated in 1-year-old Nagase analbuminemic rats (NAR) and control Sprague Dawley rats (SDR). The NAR, particularly the females, were found to be severely hyperlipidemic. Plasma total cholesterol in non-fasted animals was 6.1 +/- 0.3 mM in the female NAR vs. 2.5 +/- 0.2 mM in the female SDR (P less than 0.01). Most of the cholesterol was located in the LDL (1.019-1.063 g/ml) and HDL2 (1.063 1.125 g/ml) density range. Plasma triglycerides were 6.1 +/- 0.6 mM in the female NAR vs. 1.3 +/- 0.3 mM (P less than 0.01) in the female SDR. Plasma phospholipids were raised up to 5.4 +/- 0.3 mM vs. 2.4 +/- 0.1 mM (P less than 0.01). NAR have increased concentrations of plasma apolipoproteins A-I (about 3-4-fold) and B (about 2-fold), but the levels of apolipoproteins A-IV and E are not increased. There was less proteinuria in the male NAR than in the male SDR (P less than 0.01). Relevant histopathological findings in the NAR included hepatocytic lipofuscinosis and hemosiderosis in Kupffer cells. Tubular lesions were more common in kidneys from NAR than from SDR, and included protein casts, cortical lipofuscinosis, proximal tubular hyperplasia and proliferative interstitial nephritis. Glomerular changes were similar in both strains. Calcinosis of the aortic media and the corticomedullary region of the kidney was characteristically present in the female SDR but absent in the female NAR. Atherosclerotic lesions were not observed. In summary, 1-year-old NAR maintained on standard rat chow, are hyperlipoproteinemic. The increased levels of plasma LDL and HDL cholesterol are not associated with an increase in the incidence or severity of atherosclerotic or glomerular lesions. PMID- 1878009 TI - Effect of drinking pattern on plasma lipoproteins and body weight. AB - The effect of drinking pattern on plasma lipoproteins and body weight was examined in three groups of squirrel monkeys: (1) controls fed isocaloric liquid diet; (2) regular drinkers given liquid diet containing ethanol (EtOH) substituted isocalorically for carbohydrate at 12% of calories daily; and (3) binge drinkers fed 6% EtOH calories daily for a four-day period followed by three days of 20% EtOH to mimic a weekend bout drinking cycle. The number of calories offered per day was the same for all groups, and the average weekly EtOH consumption (12% calories) was identical for the two alcohol treatments. The entire study lasted six months. There were no significant differences in plasma cholesterol, triglyceride or liver function tests. Regular drinkers had the highest high density lipoprotein2/high density lipoprotein3 (HDL2/HDL3) protein and apolipoprotein A-I/B ratios of any group and exhibited a significant elevation in the molar plasma lecithin:cholesterol acyltransferase (LCAT) rate (nmol/min/ml). Binge drinking produced a selective increase in low density lipoprotein (LDL) cholesterol and apolipoprotein B, and a depression in the fractional LCAT rate (% esterified/min). During the course of the study, controls ate 92% of their diet while the alcohol groups each consumed 95% of the liquid diet. Despite this difference, body weight and Quetelet index (weight/height2) decreased progressively in the order controls greater than regular drinkers greater than binge drinkers. Results from our study indicate that moderate, regular daily consumption of EtOH at 12% of calories causes a modest reduction in body weight and produces a coronary protective lipoprotein profile (increases HDL2/HDL3, increases apolipoprotein A-I/B, low LDL cholesterol). By contrast, when this same average weekly dose is concentrated in a binge cycle, unfavorable alterations in lipoprotein composition (increases LDL cholesterol, increases apolipoprotein B) and metabolism (decreases LCAT activity) occur along with weight loss and depletion of body fat. These studies point to the value of the squirrel monkey model in evaluating both favorable and pathophysiological effects of chronic EtOH intake. PMID- 1878010 TI - Homocysteine content of lipoproteins in hypercholesterolemia. AB - In order to study the connection between homocysteine and lipid metabolism in atherosclerosis, homocysteine was determined in lipoprotein fractions from men with hypercholesterolemia. All lipoprotein fractions contain a considerably higher level of homocysteine in hypercholesterolemia, compared to normolipemic men, varying from 2.2 to 7.2 times higher estimated per unit volume of serum used for lipoprotein isolation, and from 2.4 to 4.1 times higher, estimated per gram protein. The largest difference in homocysteine content, estimated per gram protein, is present in the LDL fraction, amounting to 4.1 times higher in the hypercholesterolemic than the normolipemic group. In contrast, cholesterol is not higher in hypercholesterolemic than normolipemic men in any lipoprotein fraction, estimated per gram protein, and cholesterol is higher in hypercholesterolemic men only in the LDL fraction, estimated per unit volume. In both LDL and VLDL fractions homocysteine is correlated with cholesterol (r = 0.78, P less than 0.001; r = 0.59, P less than 0.01, respectively) and with protein (r = 0.72, P less than 0.01; r = 0.78, P less than 0.001, respectively). The atherogenic index for homocysteine, LDLHCy/HDLHCy, is 3.5 times higher in the hypercholesterolemic than the normolipemic group. The atherogenic index for cholesterol, LDLChol/HDLChol, is 2.2 times higher in the hypercholesterolemic than the normolipidemic group. The results suggest that analysis of the homocysteine content of the serum and lipoprotein fractions may prove to be useful for assessing risk, prognosis and response to therapy in persons with atherosclerosis. PMID- 1878011 TI - Effect of probucol on triglyceride turnover in streptozotocin-diabetic rats. AB - The long-term effect of probucol on triglyceride turnover was examined in streptozotocin (40 mg/kg) diabetic rats. Two diabetic groups were prepared: one group received a probucol-containing (1%) diet (probucol-treated diabetic) and the other standard diet (diabetic control). After 4 months of probucol diet, triglyceride turnover was estimated using Triton WR1339. In diabetic control rats, glucose, triglyceride and cholesterol concentrations in plasma and in the very low density lipoprotein (VLDL) fraction were markedly elevated and plasma insulin was suppressed compared to non-diabetic control rats. There was no significant difference in body weight, plasma glucose and insulin between the 2 diabetic groups. However, the probucol-treated diabetic group showed significantly suppressed levels of triglyceride and cholesterol in total plasma and in the VLDL fraction compared to each corresponding diabetic control value. On the other hand, there were no significant differences in triglyceride secretion rate between the 2 diabetic groups. Newly secreted VLDL particles after Triton injection from diabetic control rats were significantly cholesterol enriched and triglyceride-depleted compared to those from non-diabetic control rats. However, the composition of those from probucol-treated diabetic rats was similar to that of non-diabetic control group. Prominent hypertriglyceridemia without increase in triglyceride secretion rate in diabetic control group indicates triglyceride removal defect in diabetic rats. Significant suppression of plasma triglyceride level without changes in the triglyceride secretion rate in the probucol-treated diabetic group suggests that probucol stimulated triglyceride removal in diabetic rats. Thus, probucol might normalize VLDL composition, thereby contributing to accelerated triglyceride removal from the circulation of streptozotocin diabetic rats without affecting glucose metabolism. PMID- 1878012 TI - Platelet hypersensitivity in cholesterol-fed rabbits: enhancement of thromboxane A2-dependent and thrombin-induced, thromboxane A2-independent platelet responses. AB - Hypercholesterolemia (mean plasma cholesterol: 15 mM) was induced in rabbits by the feeding of a chow diet enriched with a low amount (0.25%, w/w) of cholesterol only. Platelet size and protein content decreased significantly, but the whole blood platelet count did not change. The platelets became enriched in cholesterol, as indicated by a significant increase in the cholesterol:phospholipid molar (C/P) ratio. Specific responses of washed platelets stimulated with various agonists were studied to determine the effects of hypercholesterolemia on the various pathways of platelet aggregation in the absence of plasma components. In platelets from hypercholesterolemic rabbits compared with controls: aggregation induced by ADP was not altered; collagen induced responses (aggregation, secretion of [14C]serotonin from prelabelled platelets, thromboxane A2 (TXA2) formation, mobilization of [3H]arachidonate from prelabelled platelets) were enhanced; with aspirin-treated platelets, aggregation induced by the TXA2 mimetic U46619 was enhanced: and thrombin-induced responses of both untreated platelets (aggregation, secretion of granule contents, TXA2 formation) and aspirin-treated platelets (aggregation) were enhanced. Thus, platelets from cholesterol-fed rabbits not only form more TXA2, but they aggregate more extensively when stimulated by its mimetic. In addition, it has not been previously recognized that these platelets are also hypersensitive to thrombin-induced aggregation that is independent of TXA2. PMID- 1878013 TI - Foam cells of the rabbit atherosclerotic plaque arrested in metaphase by colchicine show a macrophage phenotype. AB - Proliferative activity of smooth muscle cells and foam cells characterizes experimental atherosclerotic plaques as they first appear. Immunohistochemical and ultrastructural methods were applied to cells arrested in metaphase by colchicine and the phenotype of cells in mitosis was detected. Most of the metaphase arrested FC found in aortic plaques of cholesterol fed New Zealand rabbits were positive to the anti-macrophage monoclonal antibody and negative to the anti-smooth muscle actin monoclonal antibody. Moreover, most of the metaphase blocked FC had the ultrastructural features of macrophages. These preliminary results further strengthen previous observations on rabbit plaques that the FC pool is mainly constituted by macrophages and show, for the first time, that the dimension of this pool depends not only on migration of circulating monocytes but also on the in situ proliferation of macrophages. PMID- 1878014 TI - Body fat distribution affects responses to high fat cholesterol containing diet in male cynomolgus monkeys. PMID- 1878015 TI - Homocysteine content of plasma in ischemic heart disease, the reducing effect of pyridoxine, folate, cobalamin, choline, riboflavin and troxerutin. Correction of a calculation error. PMID- 1878016 TI - Searching for clues to effective use of biologic response modifiers. PMID- 1878017 TI - Psychiatric intervention after the Piper Alpha disaster. PMID- 1878018 TI - Regional anaesthesia and cough effectiveness. A study in patients undergoing caesarean section. AB - We report the results of a study of the effects of spinal and epidural anaesthesia for Caesarean section on commonly used indicators of a patient's ability to cough effectively. Both spinal and epidural anaesthesia, after the achievement of a block adequate for surgery, were associated with statistically significant decreases (p less than 0.05) in all the respiratory variables recorded: forced vital capacity, forced expiratory volume in one second, peak expiratory flow rate and maximum expiratory pressure. We conclude that although the observed changes are unlikely to impair the normal patient's ability to cough effectively in these circumstances, there may be clinically significant impairment in the presence of an inadvertently high block or in a patient with pre-existing pulmonary disease. PMID- 1878019 TI - Deafness in children. PMID- 1878020 TI - Dose-related effects of prostaglandin F2 alpha isopropylester on intraocular pressure, refraction, and pupil diameter in monkeys. AB - Topical application of Prostaglandin F2 alpha (PGF2 alpha) to the eye reduces intraocular pressure (IOP) in all mammalian species studied thus far, including humans. The L-isopropylester derivative is currently the one most commonly used in experimental and clinical studies. Dose-response relationships were determined between PGF2 alpha-IE and IOP, pupillary diameter, and refraction in ketamine anesthetized ocular normotensive cynomolgus monkeys. Single doses of 10 and 30 micrograms had smaller and less consistent but longer lasting IOP-lowering effects than repeated doses (twice daily for 3 days) of 1-5 micrograms. For repeated dosing in this manner, the just-maximal dose is probably between 2-5 micrograms, producing a approximately 70% reduction in IOP to a final IOP of approximately 5 mm Hg. Continuing treatment for up to 18 days did not further enhance the efficacy of twice daily treatment with a submaximal 1-microgram dose. Partial reversal of anesthesia-induced tonic accommodation occurred with single 10- and 30-micrograms doses and with repeated 1-microgram doses, but additional myopia of 0.5-1.5 diopters was induced with repeated higher doses. These physiologic findings and previous morphologic data are consistent with a proposed dual PG action on the ciliary muscle, one involving a short-onset long-lasting direct effect on the muscle fibers (causing relaxation and narrowing of the muscle bundles) and the second involving a slowly developing but shorter duration dissolution of the intermuscular connective tissues. PMID- 1878021 TI - Cardiopulmonary resuscitation skills of preregistration house officers: five years on. PMID- 1878022 TI - The reproducibility of the self-report of occupational exposure to asbestos and dust. AB - The reproducibility of self-reported exposure to asbestos and dust was examined in 116 male veterans who completed an initial mail survey and subsequent occupational clinic questionnaire a mean of 213 +/- 68 days later. For the 114 subjects who answered the asbestos question of the mail survey, 68 (60%) gave concordant replies, while 46 (40%) gave discordant answers later in the clinic. Of 51 subjects who answered yes to asbestos exposure in the clinic, 11 (22%) had answered no and 13 (26%) had answered not sure. Failure to note asbestos exposure could not be blamed exclusively on past, relatively low-level of exposure because many of the respondents had significant exposure histories. For dust exposure, 31 (29%) had discordant replies and 77 (71%) had concordant answers. Self-reported history of occupational exposure to asbestos and dust were not as reproducible as the smoking history and may be underreported when mail survey methods alone are used. PMID- 1878023 TI - Community obstetric care in West Berkshire. AB - OBJECTIVE: To assess the effects of a revised obstetric booking policy whereby all low risk pregnant women received their antenatal care entirely in the community. DESIGN: Comparison of the distribution of antenatal clinic attendances, transfers, and perinatal mortality rates for 1987 and 1989, before and after introduction of the revised policy. SETTING: West Berkshire Health District. SUBJECTS: All women who delivered with a registrable birth in the district in 1987 (5817 women) and 1989 (5372). MAIN OUTCOME MEASURES: Attendances at community and consultant antenatal clinics; bookings transferred from community care to consultant care; perinatal mortality rates. RESULTS: Of 5372 women delivering in West Berkshire in 1989, 3185 (58.3%) were originally booked for general practitioner-midwife care, of whom 1567 (49.2% of general practitioner-midwife bookings) were transferred to consultant care. 1618 women (30.1% of all women delivered) received their entire obstetric care from general practitioners and midwives. Attendance at hospital antenatal clinics was reduced by 16%. In 1989 the perinatal mortality rates (1987 values) for the district were 6.3 (7.6) per 1000 births overall; 8.2 (8.3) per 1000 consultant bookings; 5.0 (4.7) per 1000 for community bookings; and 10.2 (14.4) per 1000 for women transferred to consultant care. CONCLUSION: Antenatal care of low risk pregnant women may safely be provided by their general practitioner and midwife. PMID- 1878024 TI - Suicide among men in the highlands of Scotland. PMID- 1878025 TI - Accuracy of the clinical assessment of thyroid size. AB - A number of clinical decisions regarding treatment of thyroid diseases are influenced by the evaluation of thyroid size. In order to evaluate the accuracy of clinically estimated thyroid size, two experienced specialists in endocrinology and two junior doctors independently examined 53 patients. The ultrasonically-determined size was used as standard. An average error of 39% (range 0-566%) was demonstrated, the experienced doctors being more accurate than the younger ones. No relation was found between type of gland and accuracy of clinical estimation. In conclusion, palpation of the thyroid should not be used when an accurate size evaluation is considered of importance, e.g. in the estimation of radioiodine dose. PMID- 1878026 TI - Fluoridated water in day-care centers. PMID- 1878027 TI - Blood pressure control in primigravid women with mild hypertension. PMID- 1878028 TI - Esophagography and esophagoscopy. PMID- 1878029 TI - 'Reattachment of a fractured central incisor tooth fragment'. PMID- 1878030 TI - Management of bleeding in early pregnancy. PMID- 1878031 TI - Racism and psychiatry. PMID- 1878032 TI - Panic attacks in schizophrenia. PMID- 1878033 TI - A survey of dog bites in Thanet. PMID- 1878034 TI - Pulmonary dirofilariasis. PMID- 1878035 TI - Molteno implant surgery in refractory glaucoma. PMID- 1878036 TI - Gut blood flow velocities in the newborn. PMID- 1878037 TI - Management of endobronchial hemorrhage. PMID- 1878038 TI - Toxic shock syndrome. PMID- 1878039 TI - IUPAC Medicinal Chemistry report. PMID- 1878040 TI - Suggested refinements to the Vitez QA model. PMID- 1878041 TI - Amantadine for influenza A. PMID- 1878042 TI - Regulation of nickel exposure. PMID- 1878043 TI - Adolescent pregnancy. PMID- 1878044 TI - Scleral fixated intraocular lenses. PMID- 1878045 TI - Latent rabies. PMID- 1878046 TI - Papillary cystic neoplasm of the pancreas. PMID- 1878047 TI - The finding among AIDS patients of paradoxical hypouricemia in the presence of volume depletion combined with hyponatremia and high fractional excretion of sodium. PMID- 1878048 TI - A method to prevent tampering with an infusion pump. PMID- 1878049 TI - Sudden cardiac arrest during epidural anesthesia: venous air embolism? PMID- 1878050 TI - A retractor for cholecystectomy. PMID- 1878051 TI - Medication compliance in epilepsy. PMID- 1878052 TI - Superior oblique palsy as a complication of anterior ethmoidal artery ligation. PMID- 1878053 TI - Acute angle-closure glaucoma following botulinum toxin. PMID- 1878054 TI - Chemoprophylaxis for haemophilus influenzae type b. PMID- 1878055 TI - Endoscopic and histological findings in subjects with dyspepsia. PMID- 1878056 TI - Posttraumatic gustatory rhinorrhea. PMID- 1878057 TI - Effect of oral high frequency oscillation. PMID- 1878058 TI - 24-hour intragastric acidity and plasma gastrin after omeprazole treatment and after proximal gastric vagotomy in duodenal ulcer patients. PMID- 1878059 TI - Industrial veterinary medicine. PMID- 1878060 TI - Meanings of conception rate. PMID- 1878061 TI - Plasma von Willebrand factor levels and congestive heart failure. PMID- 1878062 TI - Count-based ratios for determining left ventricular volume. PMID- 1878063 TI - Myocardial viability. PMID- 1878064 TI - Periodic physician recredentialing. PMID- 1878065 TI - MRI quantification. PMID- 1878066 TI - Amiodarone-acenocoumarin interaction. PMID- 1878067 TI - Barium enema retention catheters. PMID- 1878068 TI - Residency training and abortion. PMID- 1878069 TI - Should routine liver biopsy be done for the definite diagnosis of acute fatty liver of pregnancy? PMID- 1878070 TI - Regional anaesthesia and cough effectiveness. PMID- 1878071 TI - Failure of hydrocortisone to prevent postoperative sore throat. PMID- 1878072 TI - High-performance liquid chromatographic analysis of 5-ethylpyrimidines and 5 methylpyrimidines in plasma. AB - A high-performance liquid chromatographic (HPLC) method employing a C18 reversed phase column, a mobile phase of sodium acetate and methanol, and an ultraviolet detector was developed for the analysis of 5-ethylpyrimidines and 5 methylpyrimidines in plasma. Samples were prepared for HPLC by sequential cation exchange and anion-exchange column chromatography. Linear standard curves were obtained for samples containing 0.05-50 micrograms/ml 5-ethyl-2'-deoxyuridine and 5-ethyluracil, 0.05-10 micrograms ml 5-(1-hydroxyethyl)uracil, and 0.1-50 micrograms/ml thymidine, thymine and 5-hydroxymethyluracil. Applicability of the method to determination of the kinetics of 5-ethyl-2'-deoxyuridine elimination by the isolated perfused rat liver was demonstrated; clearance of the drug was 1.29 ml/min. PMID- 1878073 TI - MDL 72222, a selective 5-HT3 receptor antagonist, suppresses voluntary ethanol consumption in alcohol-preferring rats. AB - The effect of the selective 5-HT3 receptor antagonist MDL 72222 on voluntary ethanol consumption was examined in Sardinian ethanol-preferring (SP) rats in a free choice (10% ethanol and water) experiment. SP rats consumed 8.1 +/- 1.1 g/kg ethanol daily. MDL 72222 treatment (3.0, 5.0 and 7.0 mg/kg i.p. 3 times daily for 6 days) inhibited ethanol consumption during the 6 days of treatment by 25%, 50% and 75%, respectively, without modifying total fluid intake. We suggest that 5 HT3 receptor activation plays a permissive role in alcohol preference. PMID- 1878074 TI - The value of brainstem auditory evoked potentials in early diagnosis of Wernicke's encephalopathy. AB - Statistical analysis of the interpeak latencies of brainstem auditory evoked potentials (BAEP) shows that a delayed IPL I-V is a very sensitive indicator for an early diagnosis of Wernicke's encephalopathy. In cases of uncomplicated delirium tremens no significant deviations of BAEP were found. PMID- 1878075 TI - Do alcoholic beverages have an additional effect on the postprandial gastrin response in humans? AB - The hormone gastrin plays an important role in the regulation of acid secretion in the stomach which, in turn, stimulates the digestion of food. Previous studies reported that administration of beer and wine but not ethanol and spirits increases gastrin secretion in fasting volunteers. It is not known whether alcoholic beverages combined with a normal meal have an additional effect on the postprandial gastrin response. We therefore measured the gastrin response in eight volunteers who received either alcoholic beverages (40 g alcohol) in the form of beer, red wine or spirits, or mineral water as control in combination with a dinner. Two glasses were drunk before the meal, two glasses during the meal. Plasma gastrin concentrations were twofold increased at one hour after the dinner as compared to predinner values. However, no additional effect of beer, wine or spirits on this postprandial response was seen. The present study does not support the hypothesis that the consumption of beer or wine during a meal has a positive effect on the release of gastrin and therefore most probably does not contribute to an improved digestion of food by stimulation of acid secretion. PMID- 1878076 TI - Hepatic transmethylation and blood alcohol levels. AB - Golden Syrian hamsters that have elevated hepatic alcohol dehydrogenase activity were divided into four groups and group-fed on four different liquid diets for five weeks. Group I was fed a control diet formulated for hamsters. Group II was fed the control diet containing 20 micrograms of 4 methylpyrazole per litre. Group III was fed the hamster ethanol liquid diet (ethanol amounting to 36% of total calories). Group IV was fed the ethanol diet to which 4-methylpyrazole (20 micrograms/litre) was added. Groups I, II and III were group-fed the amount consumed by Group IV on a daily basis. Upon killing the animals, blood alcohol levels were found to be elevated in Group IV but not in Group III. Hepatic methionine synthetase (MS) was inhibited in Group IV. Betaine-homocysteine methyltransferase was induced in this group to compensate for the MS inhibition and liver betaine was lowered reflecting this induction. None of these changes were seen in Group III. Since none of the animals showed an aversion to their respective diets and gained weight normally, these data indicate that it was the elevated blood levels of ethanol rather than nutritional factors that were related to the changes in methionine metabolism. PMID- 1878077 TI - Alcohol-induced depression: involvement of serotonin. AB - We examined tryptophan and serotonin (5-hydroxytryptamine) levels in the blood after consumption of alcohol. Forty-five minutes after drinking, whole blood serotonin concentration was significantly reduced, whereas no changes were observed in tryptophan level. The diurnal rhythm of 5-HT in subjects who the day before had drunk alcohol was quite different from the control group, but very similar to that of patients with depression. The results strongly suggest that the mechanism of depression after alcohol drinking may be related to serotonin. PMID- 1878078 TI - Intracerebral grafting impedes hippocampal cell loss during withdrawal after long term alcohol consumption in rats. AB - We previously found that, in the hippocampal formation as well as other central nervous system regions, withdrawal from alcohol following long periods of ingestion did not impede the ethanol-induced degenerative changes, including cell loss: on the contrary, neuronal degeneration was found to be increased in withdrawn rats. By grafting withdrawn rats either with immature hippocampal blocks or with suspensions of cultured astrocytes, we hoped to arrest the process of cell loss or even reverse it, because it is known that grafted material might display trophic and eventually protective effects in conditions of brain damage. The dentate granule and hippocampal CA3 pyramidal cells were counted both in the grafted hemisphere and in the contralateral one. Grafts of astrocyte suspensions did not interfere with the ongoing process of cell death in withdrawn rats. Conversely, grafts of hippocampal tissue impeded the degeneration observed in the granule and pyramidal cells of the grafted hemisphere, although in the contralateral one the cell loss persisted. We therefore conclude that the protective effect displayed by solid grafts might be a local process dependent on the release of diffusible trophic agents. We cannot explain the absence of any effect displayed by astroglial grafts, inasmuch as in different experimental situations such an effect was described. PMID- 1878079 TI - The urinary excretion of the collagen degradation markers pyridinoline and deoxypyridinoline in an experimental rat model of alcoholic bone disease. AB - (1) The effect of chronic (6 weeks) ethanol feeding on whole-body skeletal tissue in the rat was studied by analysis of the urinary pyridinium crosslinks of collagen, pyridinoline (PYD; found predominantly in the collagens of cartilage and bone and to a lesser extent in other tissues) and deoxypyridinoline (DPD; found only in type I collagen of bone and dentine). (2) The urinary concentrations of total, free and conjugated PYD were unaltered by ethanol feeding. In contrast, there were significant reductions in total and conjugated DPD concentrations. The reduction in the concentration of free DPD did not achieve statistical significance. The urinary PYD/DPD molar ratios, of total and conjugated forms, were increased. (3) Alcohol feeding caused the total 24 hr urinary PYD excretion to fall slightly, by 15%. There were no statistically significant effects on excretion of free and conjugated forms of PYD, nor on the free/total, free/conjugated and conjugated/total molar ratios. In contrast, the 24 hr urinary excretion of total, free and conjugated DPD was significantly reduced by 25-55%. Furthermore, the free/total and free/conjugated molar ratios were significantly increased by 40% and 80%, respectively, and the conjugated/total molar ratio was significantly reduced by 16%. (4) Data from the analysis of plasma electrolytes, enzymes and metabolites did not support the contention that the effects on collagen degradation were a result of secondary organ dysfunction due to alcohol consumption. (5) The results suggest that chronic ethanol feeding for 6 weeks is having a primary effect on skeletal tissue. A reduction in the absolute rate of bone resorption is implicated and ethanol may inhibit the normal formation of the mature crosslinks. PMID- 1878080 TI - Alcohol consumption of patients with supraventricular tachyarrhythmias other than atrial fibrillation. AB - We studied the recent alcohol consumption and other possible precipitating factors in 99 consecutive patients (53 men and 46 women) all under 65 years of age with sustained re-entry and automatic supraventricular tachyarrhythmias and compared them with those of two groups of controls. One control group was derived from the Emergency Room patients and matched for age and sex; the other group (44 men, 22 women, mean age 48.7 years) was randomly selected from the general out-of hospital population. There were 50 patients with supraventricular tachycardia, 30 with atrial flutter, and 19 with paroxysmal atrial tachycardia. Coronary heart disease (14% of patients), hypertension (10%), and dilated cardiomyopathy (6%) were the most prevalent cardiovascular diseases associated with the arrhythmias. The self-reported alcohol consumption of patients with arrhythmias during the week preceding the arrhythmia did not differ significantly from that of hospital or population controls, although significantly more patients than controls had liver enzyme levels above normal; neither were there any significant differences between the groups regarding prevalence for alcoholism as judged by the CAGE questionnaire. The results were essentially similar when patients with supraventricular tachycardia and those with intra-atrial tachyarrhythmias (flutter and paroxysmal tachycardia) were separately compared with the controls. We conclude that alcohol consumption, although a risk factor for atrial fibrillation, is not associated with the induction of other supraventricular tachyarrhythmias in patients of working age. PMID- 1878081 TI - The relationship between social skills and adolescent drinking. AB - Studies of the drinking patterns of Australian youth have revealed the widespread use of alcohol, with substantial numbers of high school students drinking on a daily basis and regularly becoming intoxicated. The present research investigated the relationship between social skills and drinking behaviour in teenagers. The Adolescent Alcohol Involvement Scale was administered to 82 males and females aged between 13 and 16 to distinguish among drinkers, problem drinkers and non drinkers. To measure social skills, the Adolescent Problem Inventory was administered to boys and the Problem Inventory for Adolescent Girls to girls. There were significant group differences on the social skills measures with non drinkers receiving the highest scores, indicating the most social skills, followed by drinkers and problem drinkers. An analysis of results showed that 11% of drinkers and 50% of problem drinkers were in the incompetent range of social skills performance while no non-drinkers scored in this range. None of the problem drinkers scored in the highly competent range of performance whereas 22% of drinkers and 40% of non-drinkers did. Results are discussed in terms of linking a number of problem behaviours in adolescence, such as drinking, smoking and delinquent behaviour, to deficits in social skills. PMID- 1878082 TI - Alcohol consumption patterns in a primary care population. AB - Over a one-year period the authors administered the Diagnostic Interview Schedule to 459 randomly selected patients attending an urban general medicine practice. Alcohol abuse and alcohol dependence disorders were diagnosed as current in 12% of the patients, while 19% of the patients met criteria for a past disorder. In addition, 11% and 3%, respectively, reported a history of previous or current heavy consumption. The lifetime prevalence of alcohol consumption disorders is significantly higher in males than females, while current disorders are significantly more common in younger than older individuals. Based upon the number of reported symptoms, patients reporting current disorders appear to have a more serious form of disease than patients reporting a past disorder. We conclude that disorders of alcohol consumption are common in our medical practice. Moreover, our findings suggest that many patients do recover from alcohol consumption disorders (i.e. are currently symptom-free by self-report) and disease severity may be an important factor in this process. PMID- 1878083 TI - Relative kindling effect of detoxification and non-detoxification admissions in alcoholics. AB - We reviewed the histories of 340 men and 60 women who were admitted for alcohol detoxification to determine if hospitalizations unrelated to detoxification increased the prevalence of seizures observed in these patients. Previous investigations on this cohort suggested that recurrent detoxification admissions increased the probability of seizure histories. Detoxification and non detoxification hospitalizations were calculated from patient reports and chart reviews on patients admitted for alcohol detoxification. Discriminant analysis of each type of hospitalization and total hospitalizations for each sex revealed an increased risk of seizure activity correlating with non-detoxification hospitalizations, but the correlation was weaker than that observed for detoxification admissions and for total admissions. This correlation between hospitalizations and seizure prevalence supports the hypothesis that recurrent alcohol withdrawal may have a kindling effect. PMID- 1878085 TI - [Dysplasia in the digestive tract]. PMID- 1878084 TI - Tumour necrosis factor and polymorphonuclear leukocytes in alcoholic hepatitis. PMID- 1878086 TI - [Gleason's classification of prostatic adenocarcinomas]. PMID- 1878087 TI - [Muir-Torre syndrome. Multiple visceral cancers associated with an isolated sebaceous epithelioma]. AB - One case of Muir-Torre Syndrome (MTS) is reported. It is characterized by an unusual association of an unique cutaneous sebaceous epithelioma and multiple visceral adenocarcinomas. The patient was a 67 year-old white woman, from a family with inherited cancer syndrome, who developed previously four colic and one endometrial carcinomas. The morphologic spectrum of the cutaneous tumors observed in the MTS is represented by kerato-acanthoma and/or sebaceous tumors as in the original case described by Torre. The cutaneous tumors are usually multiple and follow after numerous visceral cancers such as colic, endometrial, urinary, or gastric carcinomas. The visceral cancers are remarkable because of the familial character, the multiplicity of tumors and the low-grade malignancy. Our case highlights the difficulty to make an accurate diagnosis for rare histological variants of cutaneous tumors in the MTS. PMID- 1878088 TI - [Association of a pheochromocytoma and a homolateral clear cell renal carcinoma]. AB - A 61 years old man had a clear cell type carcinoma of the right kidney and a small asymptomatic homolateral adrenal pheochromocytoma. A von Hippel-Lindau disease suggested by this association was not confirmed in this case. However the measurement of plasma and urinary catecholamines, VMA and Iodine 131 MIBG (meta iodo-benzyl-guanidine) scans are usefull in case of clinical doubt in patients with renal adenocarcinoma. This observation and others in medical literature demonstrate the interest of resection of adrenal glands during a nephrectomy for adenocarcinoma. PMID- 1878089 TI - [Presentation of standardized forms for studying surgical specimens of digestive tract carcinomas]. PMID- 1878090 TI - [A case of erythema elevatum diutinum mimicking Kaposi's sarcoma]. PMID- 1878091 TI - [Inguinal hibernoma. A case report]. PMID- 1878092 TI - [Multiple stenoses in the biliary tract]. PMID- 1878093 TI - [Arterial pathology of competition cyclists]. PMID- 1878094 TI - Long-term consequences of CNS treatment for childhood cancer, Part I: Pathologic consequences and potential for oncogenesis. AB - The pathologic changes associated with the treatment of cancer of the nervous system are reviewed. Computed tomographic, magnetic resonance imaging, and positron emission tomographic findings of these abnormalities are described, followed by discussion of the known histopathologic features. For the most part, pathologic effects are primary vascular and/or demyelinating. We review each of these effects at all levels of the neural axis. This review concludes with a discussion of the risk of developing second malignancies. Although this complication is infrequent, the likelihood that survivors of childhood cancer will develop a second malignancy is 10 times that of age-matched controls. This phenomenon in part relates to genetic predisposition, environmental factors, and host susceptibility. These qualifications not withstanding, most studies implicate central nervous system radiation with and without chemotherapy as the primary etiology for second malignancies. PMID- 1878095 TI - MRI following severe perinatal asphyxia: preliminary experience. AB - In 30 children suffering from severe perinatal asphyxia an attempt was made to determine the early prognostic signs of severe hypoxic-ischemic brain injury with magnetic resonance imaging (MRI). Ten early (1-4 days of age), 16 intermediate (2 4 weeks of age), and 38 late MRI (older than 1 month of age) procedures were performed on a 2.35 T MR-system. Severe cerebral necrosis was suspected by T2 hyperintensity of the white matter, with blurred limits to the cortex in early MRI, and was confirmed by T1 hyperintensity of the cortex in intermediate MRI. Severe cerebral necrosis was established at 3 months of age. Of the 11 children with this pattern (group A), 8 had severe and 3 had moderate cerebral palsy on subsequent examination. Thirteen children (group B) had normal late MRI scans; none developed severe cerebral palsy or marked mental retardation. Two children (group C) had focal ischemic lesions. Four children had intracranial hemorrhage (group D). Groups A and B did not differ in the severity of their perinatal histories and findings, suggesting that MRI during the first 3 months is of significant prognostic value. PMID- 1878096 TI - Tentorial subdural hemorrhage in term newborns: ultrasonographic diagnosis and clinical correlates. AB - Tentorial subdural hemorrhage with its supratentorial and infratentorial extensions were diagnosed by cranial ultrasonography and computed tomography in 9 term newborns. Vacuum extraction or forceps delivery was used in 6 patients. Abnormal neurologic manifestations developed after a period of normality in 8 patients. Increased intracranial pressure was the most common presentation. All patients had hemorrhage at the falcotentorial junction near the incisura; 5 also had hemorrhage around the tentorial leaflet. Posterior fossa retrocerebellar subdural hemorrhage developed in 5 patients and posterior interhemispheric subdural hemorrhage developed in 4. All 6 patients who received conservative treatment had normal neurodevelopmental outcomes. Of the other 3 patients upon whom suboccipital craniotomies were performed, only 1 had a normal outcome. Although it localized the tentorial subdural hemorrhage either at the incisura area or at the tentorial leaflet, ultrasonography failed to identify all patients with retrocerebellar or posterior interhemispheric subdural hemorrhage. Parturitional tentorial subdural hemorrhage may not be uncommon. Ultrasonography and computed tomography are complementary in the diagnosis. Surgical decompression of the posterior fossa subdural hematoma is necessary only in the presence of acute hydrocephalus or signs of brainstem compression. PMID- 1878097 TI - Cortical blindness in children: a study of etiology and prognosis. AB - Thirty-four children (20 boys, 14 girls) with congenital and acquired cortical blindness were analyzed for visual outcome in relation to etiology, visual evoked potentials, electroencephalography, and cranial computed tomography. All 7 children with congenital cortical blindness remained blind on subsequent examination. Of the 27 children with acquired blindness, 16 (59%) had poor visual outcome. Poor visual outcome occurred in those with cardiac arrest, hypoxia, status epilepticus, intracranial hemorrhage, cerebral thrombosis, and head trauma. Good visual outcome occurred in children with hypotensive episodes after cardiac surgery. Of the 12 children with recovery of vision, the interval from acute loss of vision to partial or total recovery was 2 weeks to 5 months. Seven children had complete recovery of vision with no residual visual field defect. The majority of children (87%) had focal or multifocal spike-and-waves and slow sharp-wave discharges on electroencephalography. None had photic recruitment response or occipital spike-and-wave discharges. Flash visual evoked potential studies performed during acute episodes of cortical blindness documented 11 with absent response, 10 with bilateral increases in latency, and 6 with normal responses. There was no correlation between normal visual evoked potentials and a good visual outcome. Only 2 of 6 children with normal responses had normal vision. Abnormal or absent responses are more predictive of a poor recovery of vision because only 3 of 21 (14%) had normal vision on subsequent examination. Abnormal electroencephalographic findings with focal or multifocal spike-and-wave discharges or cerebral atrophy on cranial computed tomography are also poor prognostic signs. PMID- 1878098 TI - Membrane cerebral lipids in Rett syndrome. AB - The lipid membrane composition of cerebral tissue from 5 patients with classic Rett syndrome, ages 12-30 years, and from 14 age-matched controls was studied. The results demonstrated a selective loss of myelin-associated lipids and an enrichment of gangliosides in temporal white matter. The ganglioside pattern revealed an increase of astroglial cell-associated gangliosides and reduced proportions of gangliosides GD1a and GT1b. This latter finding may be crucial in synaptic function. The fatty acid compositions of ethanolamine phosphoglyceride, choline phosphoglyceride, and galactosylceramide were normal. PMID- 1878099 TI - Magnetic resonance imaging in preterm infants. AB - Magnetic resonance imaging was performed in 9 preterm infants at 37-43 weeks postmenstrual age. They all were born at 26-35 weeks gestation. Myelination was graded according to its most cephalic location. Myelination pattern 2 (myelination observed in the posterior limb of the internal capsule and adjacent structures of the thalamus and lenticular nucleus) was demonstrated in 2 infants, pattern 3 (myelination of the corona radiata) in 3 infants, and pattern 4 (myelination of the centrum semiovale) in 4 infants. Bilateral low intensity areas were found on T1-weighted images in 7 infants and a ribbon-like, high intensity was observed in 5. These findings revealed a wide variety of magnetic resonance imaging appearance in apparently normal preterm infants. Caution is needed in interpreting the pathologic nature of such features in preterm infants during the perinatal period. PMID- 1878100 TI - Phasic sleep components in infants with cyanosis during feeding. AB - Although brainstem immaturity has been postulated as one of the pathogenesis underlying cyanosis during feeding (CDF), there has been no widely accepted physiologic parameter that reflects brainstem function. We recently proposed that the dissociation index (DI), one of the phasic sleep parameters, is a reliable and quantitative sleep parameter for assessing brainstem maturation during early infancy. In the present study, we evaluated brainstem impairment in infants with CDF using phasic sleep components. Polysomnographies were obtained for 12 infants with CDF who were equally divided into 2 groups: one had or subsequently experienced apparent life-threatening events or sudden infant death syndrome (ALTE-SIDS group) and the other did not (CDF group). Rapid eye movement density and the number of gross movements (body movements, including the trunk, lasting greater than or equal to 2 sec) in the patients were identical to those in the controls. In the CDF group, the decrease of the average DI value from the controls was significantly less than the decrease in the ALTE-SIDS group. CDF may be a mild expression of brainstem immaturity. DI appears to be useful when evaluating infants with cyanosis during feeding. PMID- 1878101 TI - Acute hemiplegia associated with HIV infection. AB - An acute hemiplegia secondary to a large cerebral infarct is described in a 16 month-old infant with congenitally-acquired human immunodeficiency virus infection. Serial imaging studies during the next year documented improvement in his hemiplegia and a static underlying human immunodeficiency virus encephalopathy. Acquired immunodeficiency syndrome should be included in the differential diagnosis of children with acute hemiplegia. PMID- 1878102 TI - Ultrasonographic findings in thalamus and basal ganglia in term asphyxiated infants. AB - Three severely asphyxiated term neonates demonstrated bilateral hyperechogenicity in the thalamus and basal ganglia. During evolution, areas of attenuated echogenicity appeared in these structures at the same time as periventricular cysts were evident in 2 patients with coexistent periventricular leukomalacia. All 3 patients developed ventricular dilatation; in the 2 patients with periventricular leukomalacia, the ventricular border was irregular in the outer (dorsal) margin, and interhemispheric fissures were widened as a manifestation of cerebral atrophy. Furthermore, the thalamic inner (ventral) margins of the lateral ventricles were irregular in all 3 patients. This previously unrecognized finding points to a particular form of cerebral atrophy localized in the gangliothalamic region that contributes to the development of ventriculomegaly. The reported sonographic sequence implies profound damage in the thalamus and basal ganglia in asphyxiated infants which undoubtedly has contributed to the poor outcomes of our patients. PMID- 1878103 TI - Acute dyskinesias in young asthmatics treated with theophylline. AB - Two young children, 5 and 30 months of age, developed acute transient dyskinesias. The novel features of these patients were classic orobuccal-lingual dyskinesias, their young ages, and the association with asthma and theophylline. The movements resembled tardive dyskinesias of older patients on neuroleptics, but neither patient had any exposure to neuroleptic drugs. Choreiform movements were moderately severe and remitted several hours after discontinuation of theophylline or over days in the patient who remained on the drug. No symptomatic treatment of dyskinesia was required. Both infants otherwise had normal neurologic examinations with no clinical evidence of meningoencephalitis, seizures, or stroke. Both infants required hospitalization for respiratory distress, but not intensive care. The highest theophylline levels measured in these patients were 22 and 25 micrograms/ml and levels determined closest to the appearance of dyskinesias were lower. Urine toxicology screen for other drugs and routine blood work were normal. The infants, examined subsequently for 1 1/2-2 years for asthma, have demonstrated no reappearance of dyskinesias or other neurologic abnormalities. We propose an interaction of theophylline, hypoxemia, or other factors related to asthma in the pathophysiology of reversible dyskinesia in our patients. PMID- 1878104 TI - Monomelic amyotrophy in siblings. AB - Monomelic amyotrophy is a rare, benign motor neuron disorder. Electrophysiologic studies are suggestive of localized chronic anterior horn cell disease. Two young siblings are reported with monomelic amyotrophy who had proximal muscle weakness confined to one arm. We propose that monomelic amyotrophy, at least in this family, is inherited as an autosomal recessive trait. PMID- 1878105 TI - Leber congenital amaurosis in siblings with diffuse dysmyelination. AB - Two brothers are described with the previously unrecognized combination of Leber amaurosis and abnormal myelin detected by magnetic resonance imaging. Both have evidence of delayed psychomotor development and one has autistic features. A possible relationship with infantile autism or a peroxisomal dysfunction syndrome is explored. No peroxisomal defect was found in these patients. PMID- 1878106 TI - Marine biosurfactants, I. Screening for biosurfactants among crude oil degrading marine microorganisms from the North Sea. AB - Three bacterial strains of marine origin were isolated during a screening for biosurfactants among n-alkane degrading microorganisms. One strain-identified as Alcaligenes sp. MM1-produced a novel glucose lipid. In the case of Arthrobacter sp. EK 1 the well-known trehalose tetraester was found as major component. From another pure culture classified as Arthrobacter sp. SI 1, extracellular emulsifying agents with properties indicating high molecular weight substances were detected. Furthermore trehalose corynomycolates were found at up to 2 g/l. The isolated biosurfactants showed good interfacial and emulsifying properties. PMID- 1878108 TI - Marine biosurfactants, III. Toxicity testing with marine microorganisms and comparison with synthetic surfactants. AB - Eight synthetic and nine biogenetic surfactants were tested on their toxicity. Because of their possible application as oil dispersants against oil slicks on sea, the test organisms used were marine microorganisms (mixed and pure cultures of bacteria, microalgae, and protozoa). Bacterial growth was hardly effected or stimulated, whilst that of algae and flagellates was reduced. All substances tested were biodegraded in sea water. The bioluminescence of Photobacter phosphoreum (Microtox test) was the most sensitive test system used. A ranking shows that most biogenetic surfactants were less toxic than synthetic surfactants. No toxicity could be detected with the glucose-lipid GL, produced by the marine bacterium Alcaligenes sp. MM1. PMID- 1878107 TI - Marine biosurfactants, II. Production and characterization of an anionic trehalose tetraester from the marine bacterium Arthrobacter sp. EK 1. AB - Within a screening for biosurfactants we could isolate various n-alkanes utilizing marine bacteria which were capable of synthesizing glycolipids. One strain was identified as Arthrobacter sp. EK 1 which produced trehalose lipids. After purification by column and thick layer chromatography the main fraction, an anionic 2,3,4,2'-trehalose tetraester, was obtained. The chain lengths of fatty acids ranged from 8 up to 14, furthermore succinate could be detected. Since the place of substitution of succinate has so far not been cited in literature, a definitive structural elucidation was carried out chemically by hydroboration and by 1H, 2D1H, 13C and 13C-1H correlation NMR measurements. All investigations confirmed the exact position of succinate at C 2 atom of trehalose. After improvement of growth conditions the production of the trehalose tetraester increased up to 4.8 milligrams during a fermentation in 20 l bioreactor under nitrogen limitation. PMID- 1878109 TI - Synthesis and biological behavior of a boronated analogue of the antiestrogen U 23,469-M. AB - A boronated analogue of the antiestrogen U 23,469-M (D. Lednicer, D. W. Emmert, S. C. Lyster, and G. W. Duncan, J. Med. Chem. 12, 881 (1969] was prepared, for possible use in neutron capture therapy of estrogen receptor-positive tumors. In this analogue, the terminal OH group was replaced by a B-decachloro-o-carboranyl residue. This compound showed a large, non-specific uptake in ZR 75-1 breast cancer-derived cells. It could partially inhibit the uptake of estradiol in these cells. Accumulation in the cells at physiologically obtainable concentrations was, however, too low to envisage a therapeutic effect following thermal neutron irradiation. PMID- 1878110 TI - Characterization of two thioredoxins in pig heart including a new mitochondrial protein. AB - Heart tissue contains two different thioredoxins. One is a specific mitochondrial protein and is best prepared from pre-isolated, intact heart mitochondria (mt thioredoxin) whereas mitochondria-depleted tissue homogenates contain the major cellular thioredoxin of cytoplasmic origin (c-thioredoxin). Both heat-stable proteins are clearly differentiated chromatographically. They exhibit slightly different molecular weights (12,300 vs. 12,000) and isoelectric points (4.7 vs. 4.8) but differ remarkably in their cysteine content: mt-Thioredoxin has two cysteine residues like the bacterial proteins, and c-thioredoxin possesses six cysteines. Heart extracts were also shown to contain a NADPH-specific thioredoxin reductase of the known mammalian type. A specific function or target enzyme of mt thioredoxin has not as yet been established. PMID- 1878111 TI - Cataract induction by 1,2-naphthoquinone. I. Studies on the redox properties of bovine lens proteins. AB - Conditions of oxidative stress may lead to cataract formation. Reaction of certain flavoproteins, the NADH: oxidoreductases, with different quinones is well known to form hydrogen-peroxide. This reaction was investigated to get more information on cataract induction by naphthalene and its quinone metabolites. Protein extracts from bovine lens cortex exhibit "diaphorase" activity, indicated as dye reduction in the presence of NADH and dichlorophenol-indophenol (DCPIP) or ferricyanide. Different redox cycling compounds are shown to be active in this "diaphorase" reaction by lens protein extract (LCE): Oxygen consumption can be detected in the presence of pyrroloquinoline quinone and juglone whereas 1,4 naphthoquinone, menadione and paraquat are no redox cyclists in this flavoprotein catalyzed reaction. PMID- 1878112 TI - Cataract induction by 1,2-naphthoquinone. II. Mechanism of hydrogenperoxide formation and inhibition by iodide. AB - Naphthalene cataract is probably due to peroxide production through naphthoquinone (NQ) redox cycling and/or glutathione conjugation. Both mechanisms yield losses of essential SH-groups in cristallins and are thus probably involved in protein modification finally visible as lens opacity. 1,2-Naphthoquinone produces H2O2 in the presence of either ascorbate, glutathione, NADH or--to a lesser extend--by homogenates of lens protein preparations. In the presence of 1,2-naphthoquinone and the above reductive additions, both, oxygen uptake and H2O2 formation can be observed. Reductive oxygen activation in these systems are diminuated by iodide in a concentration-dependent manner. Since maleimide-treated proteins are less capable to activate oxygen by 1,2-naphthoquinone, a direct oxygen activation by the interactions of 1,2-naphthoquinone with protein-SH is indicated. Catalysis of "diaphorase"-type (dia) enzymes via NADH--dia--1,2-NQ--O2 seems not to operate in hydrogenperoxide production during 1,2-naphthoquinone lens toxicity. PMID- 1878113 TI - On the relationships between the genetic code coevolution hypothesis and the physicochemical hypothesis. AB - This paper analyzes the relationships between the genetic code coevolution hypothesis and the physicochemical hypothesis by means of a comparative study of the precursor-product amino acid pairs on which the former hypothesis is based. Even if the coevolution between the biosynthetic relationships of amino acids and the organization of the genetic code is not questioned in this paper, the results and the arguments used lead us to believe that the selective pressures considered essential by the physicochemical postulates, played a more active role than that of the precursor-product relationships in defining the allocation of these amino acids in the genetic code. It is furthermore pointed out that the two evolutionary hypothesis might be aspects of the same selective pressure, and thus difficult to differentiate. PMID- 1878114 TI - Partial characterization of anti-HLA class II antibodies isolated by aid of sepharose-peptide immunoadsorbents. AB - Synthetic peptides selected from HLA-DQ and HLA-DP glycoproteins were coupled to Sepharose, and used for the isolation of anti-HLA Class II antibodies from the immune sera of rabbits immunized with human lymphoblastoid cells expressing Class II antigens. Antibodies from early and late bleedings displayed remarkable differences in affinity for peptides and for soluable membrane proteins: these differences might be due to an early immune response directed preferentially against surface linear determinants, and to a late response to assembled (discontinuous) sites. The possibility that such antibodies might be used for the identification of amino acid stretches involved in the formation of the same assembled determinant is considered. PMID- 1878115 TI - Legislative decisions: death and taxes. PMID- 1878116 TI - Topical wound management. A discussion of the use of povidone-iodine. PMID- 1878117 TI - Collaboration with a vendor. PMID- 1878118 TI - Clinical evaluation of a polymeric membrane dressing in the treatment of dermal ulcers. PMID- 1878119 TI - Financial repercussions of incontinence management. PMID- 1878120 TI - Convincing the non-compliant patient to change his behavior. PMID- 1878121 TI - The management of selected complications following ileo-anal anastomosis with pouch reservoir. Part I: Complications following stage I procedure. PMID- 1878122 TI - Resolving the dressing dilemma: selecting wound dressing by category. PMID- 1878123 TI - Achieving a state of urinary continence for residents of nursing facilities. Part I: The history and physical examination. PMID- 1878124 TI - Phospholipase A2--a mediator between proximal and distal effectors of inflammation. AB - Phospholipase A2 (PLA2) is known to play an important intracellular role in inflammatory processes but does it also perform a vital function extracellularly? Here, W. Pruzanski and P. Vadas marshall the evidence supporting PLA2 as a mediator of inflammation, specifically in linking local and systemic effects. PMID- 1878125 TI - Staphylococcal-enterotoxin-dependent cell-mediated cytotoxicity. AB - T cells equipped with sophisticated TCR and MHC recognition structures, an efficient cytokine communication network and lethal cytotoxic effector functions constitute one of the bulwarks of the mammalian immune system. However, infective agents have developed strategies to undermine T-cell immunity; for example, certain bacterial toxins serve as 'superantigens' by binding to preserved determinants on MHC class-II-encoded proteins and activating T cells expressing particular sequences of TCR V beta gene products. In this paper, Mikael Dohlsten and colleagues present evidence suggesting that these bacterial superantigens direct T cells to eradicate MHC class-II-expressing antigen-presenting cells, thus counteracting specific T-cell functions. PMID- 1878126 TI - Thyroid-associated ophthalmopathy--a model for the association of organ-specific autoimmune disorders. AB - The development of a characteristic ophthalmopathy is a feature of autoimmune diseases of the thyroid. The link between the conditions has not yet been discovered, but here Jack Wall and colleagues develop the theory that an autoimmune response to a 64 kDa antigen expressed on both thyroid and eye muscle membranes is responsible for this thyroid-associated ophthalmopathy. PMID- 1878127 TI - Second generation immune networks. AB - Network approaches have had little impact on immunology because they have addressed the wrong questions. They have concentrated on the regulation of clonal immune responses rather than on the supraclonal properties of the immune system that emerge from its network organization, such as natural tolerance and memory. Theoretical advances, observations in unimmunized mice and humans, and the success of novel therapeutics in autoimmune diseases have recently promoted a new burst of research on the structure, temporal dynamics and metadynamical plasticity of immune networks. PMID- 1878128 TI - The discovery of thyroid autoimmunity. PMID- 1878129 TI - Allelic variations of human TCR V gene products. PMID- 1878130 TI - HIV and idiotypic T-cell regulation. PMID- 1878131 TI - Tolerance and immune regulation. AB - Understanding of both the phenomenon of immunological tolerance and the mechanisms by which it is achieved is rapidly advancing, as was evident from a recent meeting. This report summarizes key developments in both T- and B-cell biology. PMID- 1878132 TI - Immunotherapy of rheumatic diseases--practice and prospects. AB - Present treatments for rheumatic diseases are both toxic to patients and largely ineffective in modifying the disease process. This report, based on a meeting recently held in London, investigates how far recent molecular and immunological advances can be converted into more effective, less toxic and, above all, more specific therapies. PMID- 1878133 TI - Primitive cytokines: harbingers of vertebrate defense. AB - The evolution of the immune system has awarded cytokines a key role as coordinators of the immune response. The exquisite action of cytokines in fine tuning and controlling the response raises the question of whether or not these molecules have been highly conserved through evolution. Gregory Beck and Gail Habicht have isolated and characterized two major cytokines, interleukin 1 and tumor necrosis factor, from invertebrates. In this article, they speculate on the possible function of these molecules and on the existence of other cytokines in invertebrates. PMID- 1878134 TI - The synergy between naive and memory T cells during activation. AB - Naive and memory T-cell subsets differ in their ability to synthesize and respond to a variety of cytokines in vitro and each subset can produce cytokines that amplify the response of the other subset. The significance of these interactions to antigen responsiveness has, until now, been unclear. In this article Arne Akbar and colleagues point out that both subsets are activated to the same extent by alloantigen and suggest that synergy may be an important event in initiating potent responses against transplanted allografts. PMID- 1878135 TI - The B-cell antigen receptor complex. PMID- 1878136 TI - Development of lectin-based idiotype vaccines for polysaccharide antigens. PMID- 1878137 TI - The effects of glucocorticoids on lymphocyte numbers. PMID- 1878138 TI - Immunology, inflammation and asthma. PMID- 1878139 TI - T cells, macrophages and platelets in asthma. AB - The role of T cells, macrophages and platelets in asthma is discussed. Peripheric T cell populations are normal as well in atopic as in non atopic. Macrophages can release histamine releasing factors and PAF in presence of allergens. Platelets stimulated by contact with allergens or PAF decreased the aggregation pattern induced by common inducers. These data show that different cells can play a role in the inflammatory process in asthma. PMID- 1878140 TI - Bronchoalveolar lavage cell data in drug-induced pneumonitis. AB - In an attempt to evaluate the diagnostic help of bronchoalveolar lavage cell data in drug-induced pneumonitis (D.I.P.), we collected through the world literature 167 cases of D.I.P. In 122 cases, data were available for individual analysis (68 associated with amiodarone prescription and 54 with other drugs). 28 drugs were incriminated. Apart from 13 cases with normal BAL cell profile, the most prominent feature in the other 109 was a lymphocyte alveolitis either pure or associated with neutrophil and/or eosinophil alveolitis along with an imbalance in T-lymphocyte phenotype. These characteristics closely resembled those observed in hypersensitivity pneumonitis due to inhalation of organic dust. Nonetheless, about one third or more of cases displayed no lymphocytosis but neutrophil and/or eosinophil alveolitis. Taken together, these findings are in no way specific for D.I.P. but could be of interest to help diagnosis and understanding of iatrogenic alveolitis, especially when a provocation test coupled with sequential BAL is performed. PMID- 1878141 TI - [Thursdays of allergy. The drug allergy]. PMID- 1878142 TI - Studies on bio-antioxidants--prooxidation of vitamin E on the autoxidation of linoleic acid in sodium dodecyl sulfate micelles. AB - The reaction of vitamin E (alpha-tocopherol) with linoleic acid containing peroxidized linoleic acid has been studied. No significant reaction was found in ethanol solution, whereas in sodium dodecyl sulfate micelles vitamin E reacted rapidly with peroxidized linoleic acid, and thereby induced the peroxidation of linoleic acid, leading to oxygen absorption. The reaction kinetics was studied in detail by u.v. spectroscopy, HPLC and ESR spectroscopy. It was found that the main product was alpha-tocopherone with alpha-tocopheroxy radical as the reaction intermediate. A mechanism involving two consecutive bimolecular reactions between peroxidized linoleic acid and alpha-tocopherol and between peroxidized linoleic acid and alpha-tocopheroxy radical, with rate constant 2.93 and 6.21 mol/L-1s-1 respectively is proposed. The micellar effect on the reaction is discussed. PMID- 1878143 TI - Correlation of annual change of luteinizing hormone-releasing hormone (LH-RH) with gonadal development in amphioxus. AB - The present study demonstrates for the first time by RIA that LH-RH is present in the heads as well as the bodies of the amphioxuses of both sexes. Gonadoliberin increases gradually during the course of gonadal development. At the time of gonadal maturity, LH-RH content reaches a maximum. The annual change of LH-RH correlates well with gonadal development and the gonadosomatic index (GSI). The reproductive season of the amphioxus covers about three months from May to July, and LH-RH content starts to increase in May (66.89 +/- 5.26 ng) and reaches the peak in June (158.57 +/- 3.17 ng), indicating that LH-RH is likely also to be involved in the reproductive activity of the chordate. This finding is of significance in understanding the evolutionary process of the reproductive endocrine in the vertebrate. PMID- 1878144 TI - Inhibitory property characterization and reactive site exploration of the arrowhead proteinase inhibitor. AB - Affinity chromatography was used to separate two components A and B of the crystalline arrowhead proteinase inhibitor. Both A and B are double-headed and multifunctional proteinase inhibitors. Inhibitor A is capable of inhibiting equimolarly trypsin and chymotrypsin simultaneously, and has a weak inhibitory activity toward kallikrein; whereas inhibitor B can inhibit two molecules of trypsin simultaneously, and shows rather higher inhibitory activity toward kallikrein than inhibitor A, but its inhibitory activity toward chymotrypsin is much weaker than that of inhibitor A. The results of chemical modification and the competitive binding of trypsin and chymotrypsin with inhibitor A showed that the two reactive sites of both inhibitors A and B are Lys and Arg residues. Among them the Lys reactive site is specific for inhibiting mainly trypsin, whereas the active domain composed of the Arg reactive site appears to be multifunctional and capable of inhibiting many different Ser proteinases. Based on the structural characteristics of inhibitors A and B, it was predicated that the two reactive sites should be located in the positions Lys-Ser (44-45) and Arg-Tyr-Lys (76-78), respectively. In inhibitor A, there exists another hydrophobic residue involved in inhibiting chymotrypsin. This residue might be situated in the reactive region composed of the Arg reactive site. PMID- 1878145 TI - Internalization of gap junctions between neuron and glial cell and formation of annular lamellar bodies in Chinese leech Whitmania pigra. AB - This paper reveals the formation of annular lamellar body (ALB) in the ganglion of leech by means of in situ fixation and the lanthanum nitrate tracer technique. This formation involves both wrapping and internalization of the gap junctions between glial processes themselves, as well as between neuron and glial process. The results indicate that there is probably an active process of internalization of membrane structures involving gap junctions between neuron and glial cell in the central nervous system in leech. The functions of ALB are discussed. PMID- 1878146 TI - [Metabolic regulation of ingestion in monogastric animals]. AB - Evidence has accumulated over the past 2 decades to show that the regulation of the fat body mass is integrated in the control of food intake. It was suggested long ago that the metabolic stimulation to eat originated from a shortage of available circulating metabolites; particularly, glucose uptake and utilization has been a central feature of many hypotheses since Mayer's glucostatic theory. In the first section of this contribution, evidence is presented that in rats and man a premeal decline in blood glucose concentration is causally related to meal initiation. The origin of the decline and the possible role of "glycemia sensitive" neurons located in the lateral hypothalamus (LH) as central sensors of this metabolic stimulus to eat are discussed. In the second section, it is suggested that LH energy utilization and ventro-medial hypothalamus (VMH) energy storage reflect metabolic change at the periphery and also determined the neuronal activity which monitors storage or mobilization of fuels into and from stores. Since glucose is a precursor of triglycerides deposited in adipose tissue and since oxidation of fatty acids in peripheral tissues has a glucose-sparing effect, circulating glucose seems a likely candidate for the signal mediating the effect of fat deposits on food intake. PMID- 1878147 TI - Age-related changes in plasma porcine growth hormone (GH) profiles and insulin like growth factor-I (IGF-I) concentrations in Large White and Meishan pigs. AB - Plasma GH profiles and IGF-I concentrations were determined in Large White intact male (LW-M), female (LW-F) and castrated male (LW-C) and in Meishan intact male (MS-M) pigs between 10 and 140 d of age. Mean GH levels slightly increased between 10 and 45 d of age in LW pigs, in connection with an alteration in the temporal distribution of GH peaks, whereas neither interpulse GH level nor maximum GH level were affected. Mean GH levels decreased after 45 d of age, in connection with a decline in maximum and interpulse GH levels. IGF-I concentrations were low between 10 and 45 d of age and increased thereafter. GH secretory profiles did not differ significantly between LW-M and LW-F at either age. Castration had no effect at 45 d of age whereas LW-C exhibited lower mean, maximum and interpulse GH levels and smaller sum of GH pulse areas and widths than LW-M or LW-F at 140 d of age. IGF-I was lower in LW-C or LW-F than in LW-M at 140 d of age. The pattern of age-related changes in GH and IGF-I was similar in MS and LW pigs. However, interpulse GH level was higher and sum of GH pulse widths was smaller in MS-M than in LW-M, whatever the age. The results indicate that: i), GH and IGF-I secretions were similar in Meishan, and Large White pigs; ii), in both breeds, GH secretion declined after 45 d of age, due to decreased maximum and interpulse GH levels; iii), sex and/or castration effects on GH and IGF-I secretion were observed after 45 d of age only. PMID- 1878148 TI - Hepatic and portal-drained viscera balances of amino acids, insulin, glucagon and gastrin in the pig after ingestion of casein or rapeseed proteins. AB - Hepatic and intestinal balances of amino acids, insulin, glucagon and gastrin were studied in 6 non-anaesthetized Large White pigs (mean body weight 64 +/- 4.8 kg) after ingestion of casein or rapeseed proteins. The animals were fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein. In addition, 2 electromagnetic flow probes were implanted, one around the portal vein and the other around the hepatic artery. After a preliminary adaptation to each diet the animals received at 1-wk intervals and according to a double latin square design, 3 test meals of 800 g each, one containing 23.2% of rapeseed concentrate (diet RA 12) and the others 13.9 or 27.8% of hydrochloric casein (diets CA 12 and CA 24). Each observation period lasted 12 h. Amino acids from all diets were very well absorbed. In 12 h, the absorption of total amino acids as a percentage of the ingested quantities was 99% for CA 12, 102% for CA 24 and 104% for RA 12. Hepatic uptake of total amino acids in 12 h expressed as a percentage of the absorbed quantities was 13% for CA 12, 66% for CA 24 and 25% for RA 12. Differences in the hepatic extraction rate of essential amino acids appeared between the 2 levels of casein ingestion and for Arg between the 2 protein sources. Whatever the nature of the ingested protein or the level of casein, the liver showed a net production of Asp and Glu. The production and hepatic balance of insulin were the lowest after ingestion of RA 12. No differences were noted in the same parameters for glucagon and gastrin. Independently of the nutritional situation, the hepatic extraction rate of insulin appeared to be higher than those of glucagon and gastrin. Our results showed that the nature as well as the level of dietary proteins have large effects on the sequence and volume of absorptive phenomena, the hepatic metabolism of nutrients, the production of gastrointestinal hormones and the non hepatic tissue disposal of absorbed nutrients. PMID- 1878149 TI - Influence of suckling and continuous cow-calf association on the resumption of post-partum ovarian function in Bos indicus cows monitored by plasma progesterone profiles. AB - The effect of suckling on post-partum ovarian function was monitored by weekly plasma progesterone determinations using enzyme immunoassay in 16 Small East African Zebu (Bos indicus) cows maintained with a fertile bull. Five cows continuously suckled their calves (COS), but starting 30 d after calving 6 cows remained with their calves which were prevented from suckling using nose plates (NOS) while 5 calves were separated and penned (PEN). The mean (+/- SE) interval from calving to first behavioural oestrus was 81 +/- 11 d and was significantly (P less than 0.001) shorter for PEN (43 +/- 10 d) than NOS (72 +/- 9 d) or COS cows (133 +/- 11 d). COS cows nonetheless weaned heavier (P less than 0.001) calves at 5 months. Ovarian activity determined by plasma progesterone levels greater than or equal to 1.3 ng/ml indicated that "silent ovulation" was initiated in 44% of cows by 40 +/- 6 d post-partum. The results indicate that continuous suckling or constant cow-calf interaction extend the post-partum anoestrous interval in Ethiopian Zebu cows. However, early-weaned calves or those on restricted suckling would need extra nutritional supplementation to ensure continued growth. PMID- 1878150 TI - In situ evaluation of the ruminal and intestinal degradability of extruded whole horse beans. AB - Four rumen and proximal duodenum fistulated non-lactating Holstein cows were used to determine the effect of extrusion at 120 degrees C of whole horse beans (Vicia faba cv Talo) on in vitro nitrogen (N) solubility and in situ degradation of dry matter (DM) and crude protein (CP) in the rumen and intestine. Cows were fed a ration of 30% whole horse beans (WHB) and 70% Italian rye-grass hay. The degradation of DM and CP was estimated using nylon bags suspended in the rumen for 2, 4, 7, 16, 24 and 48 h; the effective ruminal degradability of DM and CP was evaluated assuming a ruminal outflow rate of 0.06/h. Bags incubated in the rumen for 16 h were introduced into the small intestine through the duodenal cannula and subsequently recovered in the feces. Extrusion of WHB reduced N solubility in buffer solution (21.1 vs 74.9%). Processing diminished the effective rumen degradability of DM (74.6 vs 80.4%) and CP (70.2 vs 89.2%). Meanwhile, the amounts of DM and CP digested in the intestine increased: 9.6 vs 1.4% and 25.2 vs 3.0% respectively. Therefore, feeds containing extruded WHB increase the availability of dietary proteins in the intestine compared with diets containing raw WHB. PMID- 1878151 TI - [Angiotensin II receptors in the human placenta are type AT1]. AB - Membrane angiotensin II receptors were measured in human placenta by means of 125I [Sar1 Ile8] All (angiotensin II antagonist) and characterized by using 2 other antagonists of angiotensin II: Dup 753 and CGP 42112A. These are specific and selective ligands which enable identification of AT1 and AT2 receptor subtypes respectively. The [Sar1 Ile8] All affinity is similar (Kd approximately 1 nmol.l-1) in the 3 different placental structures examined. However, the Bmax of villous tissues is approximately 9 times higher than that observed in chorionic plate but remains near that found in basal plate. In the central area of the placenta, mean values of 125I [Sar1 Ile8] All binding observed at a single concentration of 0.15 nmol.l-1 are 242 +/- 31 fmol/mg proteins in basal plate, 300 +/- 35 in villous tissues and 36 +/- 8 in chorionic plate. The umbilical vein and arteries respectively have 8.8 +/- 4.8 and 4.0 +/- 1.7 fmol/mg protein. The subtype analysis shows that only AT1 receptor is present in placental tissues. The Bmax values as well as those obtained by the relative measurement performed at a fixed 125I [Sar1 Ile8] All concentration of 0.15 nmol.l-1 indicate that the highest concentrations of angiotensin II receptors are found in placental villous tissues. PMID- 1878152 TI - [Effect of vasopressin and indomethacin on provoked diuresis in pregnant and non pregnant Meriones crassus]. AB - The dynamics of induced diuresis was studied in Meriones crassus, a desert rodent species, during estrus and pregnancy. In response to hydration, pregnant Meriones crassus excrete excess water more rapidly than non pregnant females. Diuresis appears earlier in pregnant females indicating a more rapid inactivation of vasopressin. The possible interaction between vasopressin and prostaglandins, and its effect on renal excretion during pregnancy, was studied during arginine vasopressin treatment and after inhibition of endogenous AVP and prostaglandins. Results show a decrease in renal response to endogenous vasopressin during pregnancy in Meriones crassus, which may be due to the increase in renal prostaglandin levels. PMID- 1878153 TI - [Training: the tool against diarrhea in Mexico]. PMID- 1878154 TI - [Patterns in the household acceptance of oral rehydration therapy in a cohort of rural mothers]. AB - The household acceptance of oral rehydration solution salts was studied in a cohort of 75 rural mothers over a two year period. The study was carried out in a rural Mexican village between August 1985 and February 1988. There were 636 episodes of diarrhea, with an average of four episodes per child per year. There were no deaths due to diarrhea or its complications and only 2% of these episodes required the use of parenteral solutions. Acceptance of oral rehydration remained around 50% during subsequent bouts of diarrhea. Variables such as a medium high socioeconomic level of the family, and the reading of journals and newspapers by the mother and the presence of water supply in the home were significantly associated with the acceptance of oral rehydration treatment. On the other hand, families classified as traditional rejected the procedure with significantly higher frequency. The data presented indicates the need for redesigning oral rehydration, treatment programs to increase their impact at the community level. PMID- 1878155 TI - [A follow-up during the first year of life of newborn infants with very low weight at birth]. AB - Groups of low-weight neonates, especially those under 1,500 g, discharged from the Intensive Care Unit, have a greater frequency of having psychoneurologic, audiologic, language and ophthalmologic scars in comparison with those neonates who suffered no complications. These frequencies vary considerably depending on different authors, the type of sequela and the duration of the follow-up. It is difficult to identify early on, which of these children will be affected in his later development. The currently used prognostic indexes have shown the importance of combining the child's psychoneurologic and biologic evolution as well as his surrounding environmental factors. Thirty-eight newborns were studied. Each weighted 1,500 g or less and were discharged from the Neonatal Intensive Care Unit. All of the patients were subsequently evaluated by specialists in Neurology, Psychology, Social Communication, Neuromotor Rehabilitation and Ophthalmology at 3, 6, 9 and 12 months of age (37 weeks) and included in a study conducted by the Program for Pediatric Follow-up at the National Institute of Perinatology. In general, the number of abnormalities found in each of the specialties during the first months of life was notorious, which later decreased as the child got older. For example, Neurology found abnormalities at 3 months in a proportion of 0.61 and at 12 months, it decreased to 0.19 (P less than 0.001). During neuromotor stimulation something similar was seen at three months a proportion of 0.39 abnormalities were recorded while at 12 months this decreased to 0.18. The human communication tests showed a proportion of 0.32 at 3 months and 0.10 at 12 months (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878156 TI - [The neurological and psychomotor evolution at 2 years of age of newborn infants who underwent assisted ventilation]. AB - It is important to evaluate the development of neonates submitted to assisted ventilation since it is one of the most commonly used procedures in patients with respiratory failure. A group of 50 neonates who had been submitted to assisted ventilation were studied and compared to another group of 50 children with the same inclusion criteria, except for the fact that they had not needed ventilation. They were each evaluated since birth and thereafter every two months during their first year of life and every three months in the second year. The Amiel Tison Neurological Assessment was used to evaluate the children during the first year while the Mayo Clinic General Neurological Exploration adapted for nursing children was applied during the following year. In assessing psychomotor development, the Brunette Lezine Scale, standardized for Mexican children, was used. For practical purposes, a sample of the results obtained during the second year are presented while some pertinent variables are commented on. For those included in the ventilated group, results show a higher frequency of hyaline membrane disease (27 cases), intraventricular hemorrhage (19), pneumonia (18), and arterious duct persistence (13). The control group showed the following frequencies, respectively: 0, 4, 5, and 4 cases. The ventilation group was found to have a statistically significant higher relative risk rate (P less than 0.05) and a higher risk for neurologic sequelae (P less than 0.001) when compared to the control group. Asphyxia and hemorrhaging were factors associated and present in the ventilated group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878157 TI - [Anthropometry at birth of the child of a mother with a change in glucose metabolism]. AB - The study compares 156 newborns whose mothers had an endocrinological diagnosis of various glucose metabolism disorders, and a control group of 42 newborn whose mothers had no glucose metabolism disorder. The entire sample including the control group had 98 males and 100 females. The study group with 156 newborns was divided into 4 groups, depending on the degree of the mother's disorder. In group 1, the baby's mothers suffered diabetes mellitus type 1; group 2, diabetes type 2; group 3, gestational diabetes; and group 4, pregnancy disorders of glucose. We observed that there were no differences among the groups in the weight/height ratio. Nevertheless there was great variability in the correlation between height and weight among the study groups. Multiplex box and whisker plots conform that intergroup dispersions in the weight height ratio was greater for the experimental group than for the control group. The pattern results was similar for the weight-head circumference ratio. We concluded that adequate control of glucose metabolism disorder during pregnancy results in product with normal growth indices. PMID- 1878158 TI - [The evolutionary anthropometric profile of the child of a mother with a change in glucose metabolism]. AB - There is not sufficient information about the follow up of children belonging to mothers with some degree of glucose metabolism disorder. At The National Institute of Perinatology were studied 151 newborn. The babies were divided into four groups. The group 1 consisting of babies born from mothers with diabetes mellitus type I; group 2 of babies born from mothers with diabetes mellitus type II; group 3 including babies from mother with gestational diabetes and group 4 babies from mothers who presented alteration in glucose metabolism during pregnancy. After the evaluation of the somatic indicator we found an harmonic behavior in group 3 in weight, height and head circumference again. The most important finding was the low correlation in anthropometry at birth and one year of age. Finally we conclude that a strict control on the follow-up of the somatic growth of children, must be achieved because the hypertrophy during the first year of age depends on sociocultural and economic patterns. PMID- 1878159 TI - [Congenital lobar emphysema]. AB - This article includes the way cases of congenital lobe emphysema were treated at the Hospital Infantil de Mexico "Federico Gomez" during 1971 to 1989. A total of 17 cases were gathered, 13 were males and 4 were females; admittance age varied from 13 days to 3 years. The children's main symptoms were respiratory failure and cyanosis. The diagnosis was enhanced by a chest X-ray where lobe hyperclarity was detected, as well as a deviation of the mediastinum and a collapsed lung. A lobectomy was performed in all cases. The upper left lobe was seen to be the most affected. Two of the children died. It is important to recognize this disease early on and conduct prompt surgical treatment. PMID- 1878160 TI - [Child abuse in a Costa Rican community]. AB - Included in this article is a summary of the information gathered during 1989, after conducting a community project dealing with the prevention and care for abused children in Canton de la Union, Provincia de Cartago. Sixty-five cases of child abuse were cared for during this period 58.5% dealt with physical harm while 41.5% included diverse forms of sexual abuse. Cases of physical abuse were equally represented in both sexes while a higher incidences of female victims was seen in cases of sexual abuse. We found that there was a greater number of types of abusers among the females (totalling 12) than among the male children (totalling 6). In over half of the cases, the children came from homes where both a paternal as well as a maternal figurehead was represented, only in 12% of the cases were the mothers single. PMID- 1878161 TI - [A comparative study between the use of the Spicer-Edwards method and the coagglutination reaction for identifying Salmonella antigens]. AB - A comparative study between tube agglutination using Spicer-Edwards antisera and a coagglutination method using Staphylococcus aureus Cowan 1 (NCTC 8530) protein A to detect Salmonella flagellar antigens was carried out. A total of 39 Salmonella strains belonging to eight serogroups of the Kauffmann-White scheme were typed by both methods. Each serogroup include monophasic and biphasic strains. Statistical analysis of the results showed that the coagglutination method was more sensitive and specific that the classic tube agglutination method normally used in different laboratories. The use of less antiserum in the coagglutination method to detect Salmonella antigens without loss of specificity or sensitivity represents an important saving for clinical laboratories and for epidemiologic research that require the identification of these antigens. PMID- 1878162 TI - [The consistency and validity of a measurement in clinical pediatric research. Its definition, evaluation and interpretation]. AB - In clinical pediatric research as in all research, one of the fundamental characteristics is the measurement of the studied features, either clinical, of laboratory or cabinet. A measurement must have two fundamental characteristics, for it to be considered as scientific: consistency and validity. The first one is centered on the variability of the measurement, which is due to the measuring instrument, to the subject or entity which is measured and to the individual or individuals who carry out the measuring, this is known as intra or interobserver variability, respectively. Validity is the fact of "actually" measuring what we want to measure. Both characteristics of measurement, are often mixed, between them and with other concepts, and this is the reason of not having a clear idea of what is the real meaning. This paper discusses the different terms that have been used for consistency and validity of a measurement. Also it points out how to assess consistency, from the validity, taking into account the measuring scale of the variables and the number of observers. Easy examples are used for the application of different formulas and for the interpretation of the results. PMID- 1878163 TI - [Intestinal malacoplakia in childhood]. PMID- 1878164 TI - Low-frequency parameterization of hydrogen bonding. AB - We review the model of the hydrogen bond developed by Lippincott and Schroeder and discuss the frequency range in which it is valid, specifically in the optical and near infrared range. We then show why and how to modify the Lippincott and Schroeder formulate to apply to the far infrared and lower ranges. The contrasts between the old and modified systems, particularly with respect to the effective force constants are worked out and plotted for an example. PMID- 1878165 TI - Theory of low-frequency vibrations in DNA macromolecules. AB - To describe low-frequency dynamics of DNA macromolecules a model is developed taking into account the hydrogen bond stretching in base pairs, the backbone flexibility and intranucleoside mobility. For double-stranded DNA the normal vibrations are found and the structure of low-frequency spectrum is determined. The agreement between theory and Raman spectroscopy data for B-DNA is demonstrated. Conformational dependences of vibration spectrum during the B----A and helix----coil DNA transitions are studied. The contribution coming from low frequency mobility to the nucleic-protein recognition processes is discussed. PMID- 1878166 TI - An algorithm for the DNA sequence generation from k-tuple word contents of the minimal number of random fragments. AB - An algorithm is described for generation of the long sequence written in a four letter alphabet from the constituent k-tuple words in the minimal number of separate, randomly defined fragments of the starting sequence. It is primarily intended for use in sequencing by hybridization (SBH) process- a potential method for sequencing human genome DNA (Drmanac et al., Genomics 4, pp. 114-128, 1989). The algorithm is based on the formerly defined rules and informative entities of the linear sequence. The algorithm requires neither knowledge on the number of appearances of a given k-tuple in sequence fragments, nor the information on which k-tuple words are on the ends of a fragment. It operates with the mixed content of k-tuples of the various lengths. The concept of the algorithm enables operations with the k-tuple sets containing false positive and false negative k tuples. The content of the false k-tuples primarily affects the completeness of the generated sequence, and its correctness in the specific cases only. The algorithm can be used for the optimization of SBH parameters in the simulation experiments, as well as for the sequence generation in the real SBH experiments on the genomic DNA. PMID- 1878167 TI - Synthesis and characterization of stereoisomers of 5,6-dihydro-5,6-dihydroxy thymidine. AB - Six products were isolated by reverse phase HPLC from the reaction of thymidine with osmium tetroxide. Four of the products were identified as stereoisomers of 5,6-dihydro-5,6-dihydroxy-thymidine (TG). The absolute configurations of these four compounds (from the shortest to the longest HPLC retention times) were determined by two-dimensional nuclear magnetic resonance spectroscopy to be (-) trans-5S,6S-, (+)-trans-5R,6R-, (-)-cis-5R,6S-, and (+)-cis-5S,6R-5,6-dihydro-5,6 dihydroxy-thymidine. The other two products were dimers with unknown linking sites. Parameters of the mass and nuclear magnetic resonance spectra are reported and discussed. PMID- 1878168 TI - The wac gene product of bacteriophage T4 contains coiled-coil structural patterns. AB - The bacteriophage T4 late gene wac (whisker antigen control) encodes the protein which forms the fibrous structure on the neck of the virion called whiskers. Amino acid sequence analysis of wac gene product, as deduced from the nucleotide sequence, indicate ten alpha-helical domains (19-40 residues long) with coiled coil structural patterns. These regions comprise about 70% of the entire 486 amino acid sequence. The alpha-helices are separated by short stretches of polypeptide chain which are similar to the loop regions of the globular protein sequences. We propose a structural model for the dimer of wac gene product molecule, that we call fibritin in which two polypeptide chains associate in a parallel fashion and form a segmented alpha-helical coiled-coil rod similar to epidermal keratins. PMID- 1878169 TI - A transition from a twice-folded structure to a hairpin in oligo(dG) in the presence of magnesium ions. AB - A long (dG)n stretch can fold twice forming an intramolecular tetrahelix stabilized by guanine tetrads and stacking interactions between them (G structure). In this paper, we show that magnesium ions induce a transition of the (dG)n stretch from the G-structure to the hairpin stabilized by Hoogsteen-like G.G base pairs (G-hairpin). This transition between the G-structure and the G hairpin is detected by chemical probing. The characteristic time of the transition for a (dG)28 at 4 degrees C exceeds five hours, which allowed us to separate these two forms by electrophoresis at low temperature. We believe that the slowness of the transition is due to the fact that half of the deoxyguanosines in the insert must change their conformation from syn to anti or vice versa. PMID- 1878170 TI - Polyelectrolyte effects on 9-aminoacridine-DNA binding. AB - The 9-aminoacridine-DNA binding curve is analyzed in two ways: with polyelectrolyte effects neglected and with polyelectrolyte effects included. It is found that the analysis which includes polyelectrolyte effects is consistent with the violation of neighbor exclusion displayed by diacridine complexes as observed by Atwell et al. and by Zimmerman and coworkers. However the analysis which neglects polyelectrolyte effects is inconsistent with the diacridine results. This comparison supports the necessity of including polyelectrolyte effects in the analysis of drug-DNA binding curves. PMID- 1878171 TI - Design and synthesis of sequence-specific DNA-binding peptides. AB - Design, synthesis and DNA binding activities of two peptides containing 32 and 102 residues are reported. A nonlinear 102-residue peptide contains four modified alpha helix-turn-alpha helix motifs of 434 cro protein. These four units are linked covalently to a carboxyterminal crosslinker containing four arms each ending with an aliphatic amino group. From CD studies we have found that in aqueous buffer in the presence of 20% trifluoroethanol the peptide residues assume alpha-helical, beta-sheet and random-coiled conformations with the alpha helical content of about 16% at room temperature. Upon complex formation between peptide and DNA, a change in the peptide conformation takes place which is consistent with an alpha - beta transition in the DNA binding alpha helix-turn alpha helix units of the peptide. Similar conformation changes are observed upon complex formation with the synthetic operator of a linear peptide containing residues 7-37 of 434 cro repressor. Evidently, in the complex, residues present in helices alpha 2 and alpha 3 of the two helix motif form a beta-hairpin which is inserted in the minor DNA groove. The last inference is supported by our observations that the two peptides can displace the minor groove-binding antibiotic distamycin A from poly(dA).poly(dT) and synthetic operator DNA. As revealed from DNase digestion studies, the nonlinear peptide binds more strongly to a pseudooperator Op1, located in the cro gene, than to the operator OR3. A difference in the specificity shown by the non-linear peptide and wild-type cro could be attributed to a flexibility of the linker chains between the DNA-binding domains in the peptide molecule as well as to a replacement of Thr-Ala in the peptide alpha 2-helices. Removal of two residues from the N-terminus of helix alpha 2 in each of the four DNA-binding domains of the peptide leads to a loss of binding specificity. PMID- 1878172 TI - Over-the-shoulder medicine. PMID- 1878173 TI - A comparison of changes in the transcutaneous oxygen tension and capillary blood flow in the skin with increasing compressive weights. AB - Two measures are being advocated to evaluate physiologic changes associated with compression of skin: transcutaneous oxygen tension (tcO2) and laser-Doppler blood flow. This study asked: 1) What changes occur in tcO2 and laser-Doppler blood flow with increasing compressive weight; and 2) do these measures respond differently to increasing weight? An indenter was used to apply incremental weight to the trochanter of healthy volunteers. During the first session, tcO2 was measured, and laser-Doppler blood flow was measured during the second session. The mean values of tcO2 and laser-Doppler blood flow were analyzed for significant changes over the range of applied weight. If significant change occurred, the polynomial that best described the data was determined. Mean values for tcO2 showed a significant decrease with increasing compressive weight. Its decrease was described by a second degree polynomial (quadratic). The weight that resulted in the tcO2 reaching zero for individual subjects ranged from 400-1000. Mean values for laser-Doppler blood flow showed a significant decrease with increased weight. The decrease was best described by a first degree polynomial (line), which is a different pattern from the tcO2. Laser-Doppler blood flow continued to decline with increasing weight beyond the point where tcO2 reached zero. During low-flow states, tissue oxygen utilization may exceed oxygen delivery and lead to ischemia even though capillary closure has not occurred. PMID- 1878174 TI - Delayed presentation of a carotid-cavernous sinus fistula in a patient with traumatic brain injury. AB - Carotid-cavernous sinus fistulas are rare complications of traumatic brain injury, facial trauma and postorthognathic surgery. A high level of clinical suspicion is necessary, particularly for patients who are unable to communicate, to establish the diagnosis. A case of delayed presentation of a carotid-cavernous sinus fistula after traumatic brain injury is presented. This case illustrates that early recognition of this disorder is crucial to prevent significant morbidity. PMID- 1878175 TI - The effect of ice on intra-articular temperature in the knee of the dog. AB - The effect of surface cooling on intra-articular temperature was examined in dogs' knees. Four treatment protocols were examined: local ice compress application for 5, 15 and 30 min and local ice bath immersion for 15 min. Intra articular temperatures were recorded using a needle microprobe inserted into the knee and continuous temperature recordings were made before, during and after the treatment. Rectal temperatures were also simultaneously recorded. Intra-articular temperatures rapidly dropped during icing. Five minutes of ice compress application resulted in a 2.2 +/- 1.2 degrees C intra-articular temperature drop with no change in rectal temperature. After 15 min of ice compress application, the joint temperature fell 4.1 +/- 1.3 degrees C with no change in rectal temperature. Thirty minutes of local ice compress application dropped the knee temperature 6.5 +/- 4.0 degrees C with a slight 0.5 +/- 0.3 degrees C drop in rectal temperature. Fifteen minutes of ice water immersion caused a much greater drop in intra-articular temperatures (20.2 +/- 8.4 degrees C) than could be achieved with ice compress. Rectal temperatures fell slightly during immersion (1.6 +/- 0.3 degrees C). After the removal of any type of cryotherapy, intra articular temperatures continued to drop for several minutes and then a prolonged rewarming period commenced. The mean time required to return to baseline intra articular temperature varied from 22-60 min, depending on the type and duration of cryotherapy. We conclude that brief periods of topical cold application to a dog's knee can induce significant and long lasting depression of intra-articular temperatures and that this is a local effect not dependent on core temperature cooling. PMID- 1878176 TI - Electromyographic feedback for learning to activate thoracic inspiratory muscles. AB - The utility of EMG feedback for modifying the muscular pattern of breathing was investigated in twenty-four subjects divided into two groups (feedback, no feedback. Each took part in three 20-min training sessions, 24 h apart. All the subjects were instructed to increase the thoracic contribution of inspired gas. The feedback subjects were shown an EMG signal of the inspiratory muscles of the upper thorax and a signal indicating their current breathing phase (inspiration or expiration). The no feedback subjects only saw the breathing phase signal. The subjects' ability to control muscular activity was assessed as the relative increase in EMG from expiration to the subsequent inspiration. Analysis of variance with group and session as factors showed that feedback subjects performed significantly better, although the improvement in performance over the sessions by the two groups was not significantly different. These results lend some support to the clinical use of EMG feedback in breathing therapy aimed at changing the thoracoabdominal distribution of ventilation. However, further research for improving learning is necessary. PMID- 1878177 TI - Motor unit firing rates in postpolio and control subjects during submaximal contraction. AB - Postpolio patients have a deficit in strength recovery after isometric activity. The cause for this is unknown, but may be the result of higher motor unit firing rates during the activity, which leads to excessive fatigue of the motor units. The purpose of this study was to determine whether postpolio subjects recruited motor units at higher firing rates than control subjects. Twelve control and seven postpolio subjects were tested for maximal voluntary contraction of the quadriceps isometrically. Randomly, subjects performed isometric contractions for five 10-s periods freely against gravity (threshold) and at 20% and 40% of maximal voluntary contraction. Decompositional motor unit electromyographic analysis was used to measure motor unit amplitude, motor unit firing rate and counted number of motor units identified. Analysis was by univariate analysis of variance. Motor unit firing rate was not significantly greater (P greater than 0.05) in postpolio subjects than control subjects at all three levels of contraction. Thus, it is unlikely that an increased motor unit firing rate leads to the deficit in recovery of strength in postpolio subjects. PMID- 1878178 TI - Experience with rehabilitation in the acquired immunodeficiency syndrome. AB - Patients with the acquired immunodeficiency syndrome (AIDS) represent a novel referral population for rehabilitation services. Limited information about the rehabilitation needs of individuals with human immunodeficiency virus infection is available. We reviewed 51 consecutive patients with AIDS referred to a rehabilitation consult service. Common problems encountered included generalized deconditioning (27%) and neurologic dysfunction (45%). Neurologic presentations were diverse and included hemiparesis, diffuse cognitive dysfunction and dementia, myelopathy, myopathy and peripheral neuropathy. Other patients were referred for wound care as well as the management of the local effects of Kaposi's sarcoma, various musculoskeletal syndromes and new onset blindness. Problems identified included impaired mobility (76%), difficulty with self-care (57%), impaired cognition (29%) and uncontrolled pain (37%). Among the rehabilitation interventions utilized were therapeutic exercise (73%), gait aids (45%), bathroom and safety equipment (45%), orthotics (29%), vocational counseling (4%), pain management (29%) and whirlpool treatments (10%). Five patients were too ill or refused treatment. We conclude that AIDS patients referred for rehabilitation have a wide variety of physical deficits, demonstrate a considerable degree of functional impairment and may require multiple rehabilitation interventions. PMID- 1878179 TI - A comparison of contractile properties in the preferred and nonpreferred leg in a mixed sample of dystrophic patients. AB - No study of how muscle contractile function is related to limb preference in human muscular dystrophy is presently available. The purpose of this study was to determine if the ankle plantarflexor (PF) and dorsiflexor (DF) muscle groups of the preferred leg are more or less affected than the nonpreferred one in a mixed sample of myotonic and limb-girdle patients. Measurements of lower limb preference were made as well as of PF and DF evoked and voluntary contractile responses. Isometric contractile properties and peak values for torque production during maximum isometric twitch and voluntary contractions were measured. No significant difference was found in terms of contractile properties between the preferred and nonpreferred leg for both DF and PF muscle groups, except for the large PF twitch torque observed in the nonpreferred side (P less than 0.05). These results, however, reveal a clear tendency for both muscle groups on the preferred side to be weaker than those on the nonpreferred side. This last finding, in conjunction with the equally if not presumably stronger PF/DF muscles on the preferred leg of healthy adult subjects, would suggest that the equivalent bilateral muscle force observed in the present study may be interpreted as giving support to the hypothesis that overwork or overuse of dystrophic muscles may be harmful in weakening the musculature. PMID- 1878180 TI - Invariant characteristics of gait initiation. AB - Studies were undertaken first to describe the invariant characteristics of gait initiation and second to better understand the function of each limb in the process of gait initiation. Analysis of variance indicated significant main effects for speed for time to onset of EMG activity and force plate recordings, time to swing toe-off and heel-strike and stance toe-off. However, when the dependent variables were expressed as a percentage of the initiation cycle, no significant main effects were noted. For the second study, two force plates were utilized, and reflective markers were placed on the sacrum and anterior superior iliac spines. The timing of heel-strike of the swing limb and toe-off of the stance limb showed a high degree of coordination in both experiments (r = 0.95 and 0.98). It was concluded that the relative invariance of selected parameters indicates that gait initiation is centrally programmed. It also appears that the swing limb, although forces were very small, is responsible for the initial weight shift to the stance limb and that the stance limb is then primarily responsible for the generation of momentum. PMID- 1878181 TI - Tethered cord syndrome complicating spina bifida occulta. A case report. AB - The insidious onset of back and/or leg pain, weakness and spasticity of the lower limb, sensory deficits and neurogenic bladder and bowel in a child with spina bifida might represent a tethered cord syndrome. A case report of a child with sudden neurologic deterioration describes this condition. The successful management in children and adults with tethered cord syndrome is improved with early recognition and careful monitoring. PMID- 1878182 TI - Recurrent severe traumatic brain injury. Series of six cases. AB - Six of 141 persons treated for severe traumatic brain injury at the Medical College of Virginia were found to have a history of similar previous injury. These cases are presented in the context of the phenomenon of recurrent severe traumatic brain injury, which has received no systematic attention in epidemiologic studies of trauma. PMID- 1878183 TI - The use of transdermal scopolamine to control drooling. A case report. AB - Drooling is a serious social handicap experienced by some neurologically impaired patients. No one method has been identified to control drooling for all patients, however, anticholinergic drugs recently have been utilized. In the case study described, transdermal scopolamine patches were found to be effective for controlling drooling in a traumatic brain-injured patient for whom more conservative methods failed. From a baseline saliva flow rate, saliva flow decreased an average of 30% with one-patch and 59% with two-patch dosing. No significant side effects were observed with treatment, and the decrease in drooling was maintained for a 4-month period. Although transdermal scopolamine may represent one acceptable facet of long-term treatment, it must be stressed that efficacy is variable across patient populations and that treatment approaches must be individualized. PMID- 1878184 TI - Positive effects of interaction coaching on infants with developmental disabilities and their mothers. AB - Modification of maternal responsivity was attempted in a study of the effects of interaction coaching. Twenty-three mothers and their infants with developmental disabilities participated in an interaction coaching component that consisted of six sessions of providing feedback to mothers about incidence of overstimulation observed on videotapes. Suggestions were given for ways to interact in a more contingently responsive manner. Compared with a control group of 17 mother-infant pairs, the interaction coaching group mothers increased responsibility and decreased stimulation. The infants were less fussy and performed better on standardized developmental assessments. PMID- 1878185 TI - Recognition of affective facial expressions by children and adolescents with and without mental retardation. AB - Children and adolescents with mental retardation were compared with children and adolescents without mental retardation on their ability to recognize facial expressions. The groups were matched for either chronological age (CA) or mental age (MA). Children and adolescents with mental retardation recognized facial expressions less accurately than did subjects without retardation who were matched on CA. The MA-matched groups showed no differences in accuracy at the younger MA but a difference was found at the older MA. However, subjects categorized as having cultural-familial retardation did not differ from subjects without retardation matched for MA at either the younger or older MA. Results suggest that children with mental retardation are less able than children without retardation to develop emotional recognition skills by observational learning. PMID- 1878187 TI - Some developmental implications of a disturbance in responding to complex environmental stimuli. AB - From infancy, normally developing children exhibit a preference for certain stimuli, such as those that contain a particular amount of complexity. As children increase in age, they become more proficient in responding to more complex multicomponent instructional stimuli. In contrast, the literature abounds with examples of children with developmental delays and handicaps who exhibit varying degrees of a disturbance in responding to complex stimuli, and research and theory suggest that the presence of a disturbance in responding to complex multicomponent stimuli may deleteriously influence their development. Based on recent research, it appears that the effects of this disturbance may be altered by teaching such children a generalized set to respond to complex multicomponent stimuli. PMID- 1878186 TI - Recognition of facial expressions of emotion by persons with mental retardation. AB - A sample of 511 children and adults with mental retardation or borderline intelligence (1 SD below the mean IQ) and children of average intelligence were tested on their ability to recognize the six basic facial expressions of emotion as they are exemplified in Ekman and Friesen's (1975) normed photographs. Each subject was shown four sets of six photographs, one of each emotion. Subjects were read 24 short stories; after each one they were asked to point to the photograph that depicted the emotion described. Children and adults with mental retardation or borderline intelligence were less proficient at identifying facial expressions of emotion than were children of average intelligence. Among individuals with mental retardation or borderline intelligence, recognition of accuracy of facial emotion increased with IQ. Among individuals with average intelligence, recognition accuracy increased with age. PMID- 1878188 TI - Typical and atypical repetitive motor behaviors in young children at risk for severe mental retardation. AB - A sample of children, ages 1 to 3 years, identified as being at risk for severe mental retardation, was observed in a semi-longitudinal study to assess their pattern of typical repetitive movements topographically similar to aberrant, stereotyped behaviors and to determine the prevalence of atypical stereotypies at this age. Frequency scores, collected using a partial-interval time-sampling procedure, were analyzed on three variables (age, time of measurement, and environmental condition) using repeated measures analysis of variance. Results were discussed in light of similar studies of infants without disabilities. PMID- 1878189 TI - Assessing the acquisition of incidental information by secondary-age students with mental retardation: comparison of response prompting strategies. AB - The effectiveness and efficiency of four response prompting conditions (progressive time delay, progressive time delay with a descriptive consequent event, system of least prompts, and system of least prompts with a descriptive consequent event) were compared. Students with moderate to severe mental retardation were taught to read functional recipe words. Maintenance and students' acquisition of incidental information were assessed when it was (a) embedded in the prompts of the system of least prompts procedure, (b) included in the descriptive praise statements following correct performance with the progressive time delay and system of least prompts procedures, and (c) not presented. A multiple probe design across behaviors, replicated across subjects, was used. Results indicated that (a) each of the procedures produced criterion level responding: (b) efficiency data on traditional measures were roughly equal; (c) maintenance checks showed no differential effects related to the instructional condition; and (d) incidental information was acquired, although it was not directly targeted for instruction. PMID- 1878190 TI - The self-injury hypothesis: addressing a neurologist's concerns. AB - Coulter (1991) concluded that a "poor study design" (p. 81) was used and my hypothesis was unproven. My article was not an experimental study in the sense of presenting experimental data intended to confirm or deny my hypothesis. Rather, it: 1. Described remarkable similarity between movements in patients with mental retardation during self-injury episodes and reports in the literature of involuntary movements during confirmed frontal lobe seizures; 2. Pointed out that the movements by some patients with mental retardation were so frequent and/or forceful that self-injury resulted; 3. Presented the hypothesis that the movements by patients with mental retardation may, in some cases, be involuntary and due to undiagnosed frontal lobe seizures; and 4. Suggested that if this hypothesis were correct, then one ought to consider what sort of treatment approaches might reduce the incidence/severity of frontal lobe seizure episodes. I agree that a well-designed experimental study to test my hypothesis would be very desirable. The preceding literature review has shown how difficult it would be using present methods to do a definitive study that rigorously confirms or rejects my hypothesis. Other approaches might be considered for testing my hypothesis with persons who are unable to give informed consent. One approach using rigorous observable criteria was suggested. In the interim, it seemed worthwhile to present my hypothesis to mental retardation professionals with the hope that others would consider this possibility and its implications for diagnosis and treatment, and the hope that some patients might benefit sooner rather than later. I appreciate Coulter's (1991) comments because they provided an opportunity to clarify potential misunderstandings. It is possible that other readers have had similar concerns, and I trust that this is the appropriate forum for addressing such matters. PMID- 1878191 TI - Ecological validity revisited: a 10-year comparison of two journals. PMID- 1878192 TI - What's in a name: a comment on Goldfarb's guest editorial. PMID- 1878193 TI - The effects of neuromuscular stimulation on muscle tone at the knee in paraplegia. AB - Resting muscle tone of the leg was measured in terms of thigh muscle stiffness and knee resonant frequency in muscles of spinal cord injured subjects who had been involved in an electrical neuromuscular stimulation training programme of the thigh muscles over at least 2 months. The thigh circumference of these patients was 6.6% larger than before training commenced (P less than 0.001) and showed increased muscle stiffness and resonant frequency compared to a similar group of paralysed subjects who had not used any neuromuscular stimulation. Resonant frequency and stiffness after the long-term training were similar to those of non-injured controls and therefore the stimulation programme seemed to reverse the effects of paralysis on muscle tone. Short periods of rest (30 min) caused increased muscle stiffness in non-injured controls and paralysed muscles trained by neuromuscular stimulation. Additional 15 min periods of neuromuscular stimulation further increased muscle stiffness in the trained muscles but also in the muscles of paralysed subjects who had no long-term neuromuscular training. In contrast, 15 min sessions of passive movement of the knee decreased muscle stiffness in long-term trained paralysed muscles and untrained paralysed muscles. Knee resonant frequency was also significantly decreased in the trained paralysed muscles. Results show that muscle tone varies depending on the amount of previous movement or rest and that although neuromuscular stimulation of paralysed muscles increases muscle stiffness and knee resonant frequency, it is in fact restoring such properties of the muscle to a state approaching that of non-injured controls. PMID- 1878194 TI - Similarities between some properties of the soma and sensory receptors of primary afferent neurones. AB - The electrical properties of the somata of neurones associated with low threshold, cutaneous mechanoreceptors were studied in young, anaesthetized rats. The adaptation properties of slowly and rapidly adapting afferents were compared by recording from the somata during mechanical stimulation of the skin and during the injection of depolarizing current pulses through the recording electrode. Membrane potential and action potential conformation were recorded from each cell, together with the axonal conduction velocity. Axonal conduction velocities were in the ranges 62-18 m/s (A alpha/beta) and 7-4 m/s (A delta). Somata with A alpha/beta-axons which were associated with slowly adapting receptors gave sustained discharges when depolarized by injected current, whereas those associated with rapidly adapting receptors gave a brief discharge only (median response: five impulses). Somata with A delta-axons had similar characteristics to fast-conducting, rapidly adapting afferents. In a separate study it was shown that, for neurones which gave an adapting response to intracellular current injection, action potentials recorded from the somata were able to follow electrical stimulation of their axons at frequencies up to 100 Hz, indicating that the adaptation of responses to mechanical stimulation in the other experiments was not due to failure of impulses to invade the somata. The results suggest that the adaptation properties of a mechanoreceptor may be due to the presence of a particular type of ionic channel in the terminals of the nerve which is also present in the membrane of its soma. PMID- 1878195 TI - Regulation of mouse mammary cell differentiation by extracellular milk proteins. AB - Differentiation of mammary epithelial cells prepared from pregnant mice was stimulated by culture on floating collagen gels in the presence of lactogenic hormones. Differentiation was measured by the induction of casein synthesis and fatty acid synthase activity, both of which increased by up to 15-fold during 12 days of culture. Addition of a 10-30 kDa fraction of goat whey proteins to culture medium from day 3 inhibited casein synthesis by greater than 20% compared with control cultures on days 4-12, and prevented further induction of fatty acid synthetase activity. Inhibition of secretory cell differentiation by this fraction, which is known to inhibit milk synthesis acutely in explant culture and lactating goats, suggests that similar autocrine mechanisms may mediate the sequential local effects on milk yield and cell differentiation elicited by manipulation of milking frequency or efficiency. PMID- 1878196 TI - Kinetics of lactate and glucose metabolism in the pregnant ewe and conceptus. AB - Two monotocous and two ditocous ewes were infused at 124-130 days of gestation with a mixture of L-[U-14C]lactate and D-[6-3H]glucose via a maternal or umbilical catheter, separate days being used for each infusion. Plateaux-specific radioactivities of plasma lactate and glucose were used to derive a four-pool model describing the fluxes between the lactate and glucose pools of the infused conceptus and mother. The average turnover rate of lactate was 23.3 and 13.2 mg carbon min-1 in the conceptus and 32.0 and 44.0 mg carbon min-1 in the mother for monotocous and ditocous ewes, respectively. Glycolysis rates within both conceptus and mother in all sheep were high, accounting for about 80 and 60% of the respective rates of lactate turnover. The synthesis of glucose from lactate accounted for 13 and 31% of the glucose turnover in the mother in monotocous and ditocous ewes, respectively, but was insignificant in the conceptus. Glycolysis within the conceptus used only glucose which had entered and mixed with the conceptus glucose pool; there was no direct transfer of carbon from the maternal glucose pool to the conceptus lactate pool. This finding is an important validation for the use of tracer methods to determine glucose use within the whole conceptus rather than within fetal corporeal tissues alone. PMID- 1878197 TI - The effect of distension of the urinary bladder on coronary blood flow in anesthetized dogs. AB - To determine whether distension of the urinary bladder reflexly affects coronary blood flow, experiments were performed in eleven dogs anaesthetized with sodium pentobarbitone. Both ureters were cannulated and the urinary bladder was distended with warm Ringer solution at a steady intravesical pressure. Arterial blood pressure was prevented from changing by a pressurized reservoir of warm Ringer solution connected to the femoral arteries. Coronary blood flow was measured with an electromagnetic flowmeter positioned around the origin of the left circumflex coronary artery. When the reflex increase in heart rate was prevented by atrial pacing in seven dogs, distension of the urinary bladder always caused a decrease in mean coronary blood flow. Similar results were obtained in all eleven dogs after administration of propranolol. The decrease in mean coronary blood flow was significantly reduced by atropine or bilateral cervical vagotomy, and was abolished by bretylium tosylate. The results showed that distension of the urinary bladder reflexly decreased mean coronary blood flow, a response involving efferent cardiac vagal and sympathetic pathways. PMID- 1878198 TI - Components of transmembrane potassium (86Rb+) flux during evoked tension development in dog saphenous vein: contribution of the Na(+)-K+ pump. AB - The relationship between the concurrent increase in net K+ efflux and isometric tension development has been studied in perifused dog saphenous vein strips using 86Rb+ as a marker for K+. Noradrenaline, acting through alpha-adrenoceptors, or depolarization induced by raised extracellular K+ (in the presence of an alpha adrenoceptor antagonist) increased both 86Rb+ efflux and isometric tension. However, even with a high concentration of K+ (120 mmol l-1) the evoked changes in 86Rb+ efflux and tension were small compared with those produced by noradrenaline. There was a linear relationship between 86Rb+ efflux and tension maintained throughout the time course of each evoked response. This linear relationship was the same for each response evoked throughout the concentration range of noradrenaline (1-100 mumol l-1) or K+ (30-120 mmol l-1) used. Substitution of extracellular Ca2+ by Ba2+ did not alter either basal tension or 86Rb+ efflux; nor did it alter either the magnitude of noradrenaline-evoked changes in 86Rb+ efflux or tension, or the slope of the relationship between the two seen with Ca2+. The cardioactive steroid, acetylstrophanthidin, altered the evoked response to exogenous noradrenaline and to K+ depolarization in that there was now a significant increase in 86Rb+ efflux relative to tension, although the linear relationship between the two was maintained. In the nominal absence of extracellular Ca2+ the increase in 86Rb+ efflux produced by exogenous noradrenaline was maintained but the evoked increased in tension was reduced. The data shows for dog saphenous vein: (a) that gross evoked 86Rb+ efflux is attenuated by an active backflux mediated by the sodium-potassium pump and (b) that 86Rb+ efflux can occur through a membrane potential-activated pathway and through an independent alpha-adrenoceptor-activated pathway but although the linear relationship between 86Rb+ efflux and tension can be best explained by their co-dependence upon Ca2+, the present experiments provide no objective evidence for an internal calcium-activated pathway. PMID- 1878199 TI - The effects of cholesterol depletion on the sodium pump in human red cells. AB - Sodium pump function has been studied in human erythrocytes depleted of membrane cholesterol by incubation with phosphatidylcholine liposomes. The cells were sodium loaded by incubation in alkaline sodium phosphate and sodium pump activity was assessed by measurements of ouabain-sensitive 86Rb uptake at 37 degrees C. Cholesterol depletion had a biphasic effect; depletion by 5-25% increased sodium pump activity by a mean of 16.1% (S.D. 3.2%), whereas depletion by 35-50% decreased sodium pump activity by a mean of 14.8% (S.D. 3.8%). Cholesterol depletion had no reproducible effect on the ouabain-insensitive uptake of Rb. These results support the hypothesis that there may be an optimum membrane cholesterol content for sodium pump function. PMID- 1878200 TI - Absorption and intestinal catabolism of fatty acids in the rat: effect of chain length and unsaturation. AB - Simultaneous portal blood absorption and intestinal mucosal catabolism of labelled fatty acids were investigated. Anaesthetized adult Wistar rats were infused intraduodenally either with 90 mumol of capric (C10:0), oleic (C18:1), linoleic (C18:2) or arachidonic (C20:4) 1-14C acids or with 30 mumol of each labelled fatty acid in addition to 30 mumol of oleic acid and 30 mumol of monopalmitin. For mixed infusates, experiments were carried out with two additional long-chain fatty acids: palmitic (C16:0) and erucic (C22:1) 1-14C acids. Radioactivity was quantified in the lipids and in the catabolic products in portal blood recovered at 5 min intervals for 1 h after infusion. At the end of the experiment, the disappearance of radioactivity from the mucosa was quantified. When labelled fatty acids were infused alone, 49% of the radiolabelled lipid disappearing from the mucosa was recovered in the blood for C10:0, but only 7.8% for C18:1, 6.4% for C18:2 and 10.6% for C20:4. With mixed infusates, 41% of the radiolabelled lipid disappearing from the mucosa was recovered in the blood for C10:0 compared with 12% for C18:1, 10.2% for C18:2, 10.5% for C20:4 and 2.7% for C16:0 and 2% for C22:1. Labelled catabolites appear with the same profiles as those of the respective fatty acids in blood. These studies confirm a minor absorption into blood of long-chain fatty acids compared to the medium-chain fatty acids and highlight differences in the catabolism of the fatty acids according to their chain length and their degree of unsaturation. The differences might be related to the differences in the fatty acid hydrosolubility and to their different affinities for the I- and L-cytosolic fatty acid binding proteins. These phenomena may be important in nutrition in relation to the availability of essential fatty acids. PMID- 1878201 TI - Arginine vasopressin stimulation of chloride secretion in Madin-Darby canine renal epithelial layers. AB - Arginine vasopressin (AVP) at a concentration of 0.1 microM stimulates an inward short-circuit current (SCC) in voltage-clamped Madin-Darby canine kidney epithelial layers with a mean peak of 3.1 +/- 0.8 microA cm-2 (n = 6). The response to AVP is markedly attenuated when inward SCC is stimulated with forskolin or prostaglandin E1, in Cl(-)-free media and by the Cl(-)-transport inhibitors, bumetanide and 5-nitro-2-(3-phenylpropylamino)-benzoic acid, consistent with an AVP-stimulated basal to apical Cl- secretion. Endogenous release of prostaglandins may contribute to AVP stimulation of Cl- secretion. PMID- 1878202 TI - Automated purification of synthetic oligonucleotides. AB - We have automated the trityl-on purification of oligonucleotides by use of an XYZ axis robotic solid-phase extraction system. This greatly decreased the preparation time required for oligonucleotide purification. After about 15 min for set up of the samples and instrument, the oligonucleotides are automatically purified with a 15-min run time per sample. Thus, for example, the purification of 15 oligonucleotides requires only about 15 min of preparation time and 4 h of machine time. Yields and purity are equivalent to manual methods. PMID- 1878203 TI - Heparin-mediated transformation of Escherichia coli with Ustilago maydis DNA. AB - The inhibiton of Escherichia coli transformation caused by simple preparations of Ustilago maydis plasmid and genomic DNA can be efficiently overcome by the use of the linear polyanion heparin. Techniques using heparin have been derived that should facilitate the production and isolation of plasmids passed through Ustilago maydis and may be of benefit in other systems where similar inhibitory phenomena or low transformability are observed. PMID- 1878204 TI - 96-well plates for recombinant library maintenance and dot-blot production. PMID- 1878205 TI - Isolation and purification of specific, overlapping mRNA species by electroelution from agarose gels. PMID- 1878206 TI - DNA fragment purification: removal of agarose 10 minutes after electrophoresis. PMID- 1878207 TI - Accurate determination of pH in organic phenol and phenol:chloroform. PMID- 1878208 TI - Protein B: a versatile bacterial Fc-binding protein selective for human IgA. AB - Protein B, a selective bacterial IgA Fc-binding protein isolated from group B streptococci, has been used to quantify fluid phase and immobilized human IgA. Protein B detects both human IgA1 and IgA2 subclasses and is also reactive with secretory IgA. Protein B can be used immobilized to microtiter plates to capture IgA or following biotinylation as a tracer for fluid phase or immobilized human IgA. The studies presented here suggest protein B will prove to be a valuable reagent for quantitative immunochemical procedures involving human IgA antibodies and facilitate a variety of studies of IgA responses in man. PMID- 1878209 TI - Computer software for molecular biology. PMID- 1878210 TI - A program for computer-assisted scoring of Southern blots. AB - SCORE, a program for computer-assisted scoring of Southern blots of clone DNA, retains the use of expert human judgment while taking over much of the drudgery of the scoring task. The primary functions of the program are to help make an aligned overlay of the fluorescence gel image and the autoradiogram blot image, to keep track of band and lane locations and to store the resulting data directly into a database. Use of SCORE has resulted in greatly increased efficiency and accuracy. PMID- 1878211 TI - A computer program that simulates cloning of DNA. AB - Easy Cloner is a computer program that manipulates DNA sequences as in cloning experiments and produces maps of the resulting plasmids. The program runs in the graphics mode of an IBM PC or compatible computer and is operated by using a mouse to point to the required actions. The program is available in the public domain. PMID- 1878212 TI - Computer-aided cell colony counting. AB - Counting cell colonies is a tedious task when performed with the light microscope. Moreover, unless strict double-blind protocols are adhered to, biased counts are difficult to avoid. Presented here is a computer software application that performs accurate, reproducible cell colony counts with a minimum of user generated bias. The application is based upon the Apple IICX computer system with Image software and AppleScan. Colonies are grown on 24-well plates and prepared in such a way as to permit good quality scanning. The scans are then transferred to Image and the individual colonies in each well are counted. Good correlation with counts done by light microscopy is achieved. PMID- 1878213 TI - Estimation of sample size and assurance probability in library screening. PMID- 1878214 TI - A computer program to assist in the preparation of oligonucleotide solutions. PMID- 1878215 TI - A Macintosh computer program for designing DNA sequences that code for specific peptides and proteins. AB - A computer program (PINCERS) is described for use in the design of synthetic genes and mixed-probe DNA sequences. A protein sequence is reverse translated with generation of synonymous codons at each position producing a degenerate sequence. In order to locate potential restriction enzyme sites, the degenerate sequence is searched with a library of restriction enzymes for sites that utilize any combination of synonymous codons. These sites are indicated in a map so that they may be incorporated into the synthetic gene sequence. The program allows the user to select the appropriate codon usage table for the organism of interest and then to set a threshold usage frequency below which codons are not generated. PINCERS may also be used to assist in planning the synthesis of mixed-probe DNA sequences for cross-hybridization experiments. It can identify regions of specified length with the protein sequence that have the least overall degeneracy, thereby minimizing the number of probes to be synthesized and, therefore, maximizing the concentration of a given probe sequence. PMID- 1878216 TI - Image processing software for enhanced visualization of faint or noisy autoradiographic images. AB - A computer program for digital image processing is described which can be implemented using scanning densitometer hardware pre-existing in most biology departments plus computer video hardware which may either pre-exist in the biology department or would represent a moderate upgrade over an already planned computer purchase. The primary purpose of this computer program is to provide contrast enhancement of faint or low contrast autoradiograph images and to implement background subtraction and digital smoothing methods which permit visualization of blurry electrophoresis bands against noisy backgrounds. However, the program also has modest editing capabilities that allow its use in the routine preparation of images for publication. Finally, the program has facilities for deblurring, edge enhancement and multiple image averaging, which give it usefulness in other forms of photographic analysis. PMID- 1878217 TI - Electrophoretic gel image analysis software for the molecular biology laboratory. AB - We present GelReader 1.0, a microcomputer program designed to make precision, digital analysis of one-dimensional electrophoretic gels accessible to the molecular biology laboratory of modest means. Images of electrophoretic gels are digitized via a desktop flatbed scanner from instant photographs, autoradiograms or chromogenically stained blotting media. GelReader is then invoked to locate lanes and bands and generate a report of molecular weights of unknowns, based on specified sets of standards. Frequently used standards can be stored in the program. Lanes and bands can be added or removed, based upon users' subjective preferences. A unique lane histogram feature facilitates precise manual addition of bands missed by the software. Image enhancement features include palette manipulation, histogram equalization, shadowing and magnification. The user interface strikes a balance between program autonomy and user intervention, in recognition of the variability in electrophoretic gel quality and users' analytical needs. PMID- 1878218 TI - Pro-Search, Biblio-Links and Pro-Cite: software to gather and manage scientific and technical information. AB - Pro-Search, Biblio-Links and Pro-Cite combine to form a system for managing scientific information on the desktop. Pro-Search provides access to over 400 databases (500 on the IBM PC), Biblio-Links converts records downloaded from online, CD-ROM and diskette information services into Pro-Cite records. Pro-Cite is a full-featured bibliographic database for managing scientific literature. PMID- 1878219 TI - Nucleocytoplasmic translocation of ribosomal RNA in the rabbit blastocyst: participation of sulfhydryl groups. AB - The release of ribosomes from the nucleus in the rabbit blastocyst was investigated by pulse-labeling embryos to within 5 min of the earliest appearance of radiolabeled ribosomal RNA (rRNA) in the cytoplasmic fraction. The accumulation of radiolabeled 4.7 and 1.9 kilobase mature rRNA species in the cytoplasm was then followed during a 2 hour chase period, using polyacrylamide gel electrophoresis to identify the rRNAs. Colchicine, cytochalasin B, KCN, and EDTA were found to have no effect on the release of radiolabeled rRNA from the blastocyst nucleus during the 2 hour chase. Oligomycin, a known inhibitor of the nuclear envelope nucleoside triphosphatase, and the protein synthesis inhibitors puromycin and cycloheximide blocked rRNA release after a short delay. In contrast, actinomycin D and the sulfhydryl-reactive agents N-ethylmaleimide and diamide produced an abrupt and complete block to further rRNA release. The results indicate that ribosomes leave the nuclear compartment by an energy dependent process. They further underscore the importance of reduced sulfhydryl groups in a rapidly growing blastocyst with a high level of oxidative metabolism. PMID- 1878220 TI - Nuclear transplantation in bovine embryo: fine structural and autoradiographic studies. AB - Nucleolar fine structure, "blebbing" activity of nuclear envelope, and activation of heterogeneous nuclear RNA (hnRNA) synthesis were studied in bovine reconstructed embryos obtained by electrofusion of a single eight-cell blastomere with an enucleated oocyte. Developmental progress of nucleolar fine structure and hnRNA synthesis are arrested during three cell cycles following fusion. The activation of both appears during the eight-cell stage of the reconstructed embryo, after the same number of cell cycles after fusion as in nonmanipulated bovine embryos after fertilization. "Blebbing" activity of nuclear envelope, which is already absent in original blastomeres, reappears after fusion and continues for the next two cell cycles. From the present results, it can be concluded that the donor nuclei are arrested after fusion in morphology and function. Their reactivation corresponds to the developmental pattern typical for normal bovine embryos. PMID- 1878221 TI - Embryonic transcription in in vitro cultured bovine embryos. AB - The rate of cleavage and the onset of embryonic transcription of bovine embryos cultured in vitro (IVC) has been investigated. Embryos were derived from in vitro matured, in vitro fertilized oocytes (IVM/IVF) to improve developmental synchrony. The rate of cleavage was assessed by morphological evaluation between the one- and eight- to 16-cell stage. The rate of cleavage was found to be equivalent to that reported for in vivo recovered embryos. To assess the onset of embryonic transcription, embryos were cultured to the eight- to 16-cell stage in the presence of alpha-amanitin for various periods of time followed by two dimensional polyacrylamide gel electrophoresis. Embryos readily cleaved to the eight- to 16-cell stage in the presence of inhibitor. alpha-Amanitin-sensitive protein synthesis was first detected at 36-48 h post-insemination (hpi) and continued up to 84 hpi. We conclude that bovine embryos produced by IVM/IVF/IVC are competent to initiate embryonic transcription at 36-48 h post-insemination and suggest that in vitro-induced cleavage arrest is not due to failure of the embryonic genome to initiate transcription. PMID- 1878222 TI - Analysis of proteins expressed at the time of murine organogenesis. AB - Two-dimensional electrophoretograms were prepared from wild-type C57BL/6J embryos from day 7.5 through day 9.0 of development. This time period encompasses a critical window of development as the embryo traverses from an egg cylinder through major organogenesis. Consequently, we term this resource MOPED (for mouse organogenesis protein electrophoresis database). By resolving and analyzing the behavior of approximately 1,000 polypeptides per time point, we were able to track many of these polypeptides through this time period in development. Of special note was a burst of induced protein synthesis that was observed in mouse embryos development. Polypeptides observed in mouse embryos that match those identified previously in mouse fibroblasts were noted. Two of them (the intermediate filament-associated protein and tropomyosin-4) were significantly altered in 8.5 day embryos. As more polypeptides are designated, it will be possible to expand the known proteins in the database. MOPED establishes the patterns of synthesis of a large number of polypeptides during a crucial period of development. Thus MOPED is designed to analyze proteins relevant to mouse embryogenesis in the future. PMID- 1878223 TI - Situs inversus in the developing mouse: proteins affected by the iv mutation (genocopy) and the teratogen retinoic acid (phenocopy). AB - To decipher genes that are important in the determination of laterality, we compared two-dimensional protein gels from wild-type C57BL/6J mice and C57BL/6J mice that carried the iv mutation, which confers random determination of visceral situs. To span the time period(s) during which laterality determination occurs, we compared computer-analyzed two-dimensional protein gels from wild-type mouse embryos and iv/iv mouse embryos at 7.5, 8.0, and 8.5 days post-coitum. One polypeptide that was expressed only on day 8.0 of development and only in wild type embryos represents a particular candidate for determination of laterality. Day 8.5 postcoitum represents the earliest time in murine development that laterality is manifest. Two-dimensional gels were compared from 8.5 day embryos that were C57BL/6J wild-type, C57BL/6J iv/iv, or C57BL/6J wild-type and exposed to the teratogen retinoic acid late on day 7. Reproducible alterations of protein synthesis were observed in both the iv genocopy and retinoic acid phenocopy, yielding abnormal laterality determination. The intersection of these peptide changes identifies a protein likely to play a role in the determination of laterality. PMID- 1878224 TI - Effects of pH on the reactivation of human spermatozoa demembranated with Triton X-100. AB - The aim of this work was to study the role of different parameters involved in the motility of human spermatozoa. Human spermatozoa were totally demembranated with 0.05% Triton X-100, and the demembranation was checked using electron microscopy. We have shown that, with a concentration of ATP-Mg lower than 2 mM, a pH effect was observed with a dose-dependent motility reactivation at pH 7.1, with 14% +/- 2.0% motile cells at 1 mM ATP-Mg and a straight line velocity (VSL) of 12.0 +/- 1.4 microns/sec. However, at pH 7.8, more than 65% of the spermatozoa were reactivated with as low as 0.02 mM ATP-Mg and 77.8% +/- 2.5% of them were motile at 1 mM ATP-Mg and had a VSL of 23.4 +/- 3.9 microns/sec. The depletion of free calcium by the addition of 0.5 mM EGTA in the reactivation medium (RM) improved the percentage of motile cells and the VSL most markedly at low ATP-Mg and low pH. If no MgSO4 was added in RM, cells were not motile at pH 7.8, but 30 40% reactivated at pH 7.1. If 5 mM Ca2+ was added to the RM, up to 88% of the cells became reactivated at both pHs, but the beat frequencies were very low, suggesting different mechanisms of reactivation when Mg2+ or when Ca2+ is present in the RM. PMID- 1878225 TI - Complement component C1q and its receptor are involved in the interaction of human sperm with zona-free hamster eggs. AB - C1q is a component of the classical complement pathway that can react with the Fc fragment of immunoglobulins and with other proteins, such as fibronectin, laminin, and a specific C1q receptor present on several cell types. Given its role in many adhesion systems, mainly related to phagocytosis, we tested the effects of C1q on the interaction between human spermatozoa and zona-free hamster eggs. The presence of C1q in the medium used for gamete coincubation resulted in promotion of sperm-oolemma adhesion and an inhibition of penetration. The number of adherent sperm per egg at 5 micrograms/ml concentration was 90 +/- 35 vs. 29 +/- 7 for the control (P less than 0.001). At 1 microgram/ml, the lower concentration at which C1q had an effect, the number of penetrating sperm/egg was 0.6 vs. 1.7 for the control without C1q (P less than 0.01), and the percent of penetrated eggs was 28% vs. 85%. At 50 micrograms/ml, the percent of penetrated eggs was 7%, with a penetration index of 0.07. The addition of C1q to the medium resulted in sperm agglutination, which varied between sperm donors. The presence of C1q receptors, as detected by anti-C1qR monoclonal antibodies (Mabs), was demonstrated both on zona-free hamster eggs by immunobead rosetting and on human spermatozoa by immunobead binding and indirect immunofluorescence. Mabs directed against different epitopes of C1qR had different effects on gamete interaction, with a partial inhibition of penetration mediated by some of them. The binding of C1q to antibody-free human spermatozoa was also demonstrated both by means of indirect immunofluorescence and utilizing 125I-C1q.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878226 TI - Proteasome (multicatalytic proteinase) of sea urchin sperm and its possible participation in the acrosome reaction. AB - The egg jelly-induced acrosome reaction of the sea urchin, Strongylocentrotus intermedius, was inhibited by succinyl-Leu-Leu-Val-Tyr-4-methyl-coumaryl-7-amide (Suc-Leu-Leu-Val-Tyr-MCA), but not by Suc-Ala-Ala-Pro-Phe-MCA. The proteases with hydrolytic activity toward the former were purified from sperm extract by DEAE Sephacel and hydroxylapatite chromatographies, Sephacryl S-300 gel filtration, and heparin-Sepharose CL-6B chromatography. Two types of protease were separated, and the molecular weights were estimated to be 65 and 700 kDa, respectively, by gel filtration. The former was accompanied by hydrolytic activity toward Suc-Ala Ala-Pro-Phe-MCA, which was not hydrolyzed by the latter. Polyacrylamide gel electrophoresis of 700 kDa protease gave a single protein band under nondenaturing conditions and at least eight bands in the range of 22-33 kDa in the presence of sodium dodecyl sulfate (SDS). The substrate specificity and the inhibitor sensitivity of 700 kDa protease indicate that it contains two types of the activity, one is chymotrypsin-type and the other trypsin-type. The former activity was enhanced by poly-L-lysine or SDS. These properties of 700 kDa protease are similar to those of proteasomes (multicatalytic proteinases) isolated from various eukaryotic sources. We had previously shown that inhibitors of chymotrypsin-like proteases inhibit the increase of intracellular Ca2+ concentration by egg jelly, resulting in the inhibition of the acrosome reaction of St. intermedius (Matsumura and Aketa, Gamete Res 23:255-266, 1989). Bringing these findings together, we suggest that the chymotrypsin-like activity of sperm proteasome participates in the onset of the acrosome reaction of St. intermedius. PMID- 1878227 TI - Cross-linking a maturation-dependent ram sperm plasma membrane antigen induces the acrosome reaction. AB - ESA152 is a highly hydrophobic 18 kDa sialoglycoprotein, which becomes expressed on ram sperm in the proximal cauda epididymis. ESA 152 is expressed on all regions of the sperm surface, most strongly on the posterior region of the head, most weakly on the anterior region of the head. In this paper, we show that induction of the acrosome reaction with Ca2+ ionophore causes ESA152 to be redistributed from the posterior to the anterior region of the head plasma membrane. Cross-linking ESA152 with bivalent antibody causes similar redistribution and induces the acrosome reaction. Induction of the acrosome reaction with ESA152 antibody requires Ca2+ but is insensitive to (10 ng/ml) pertussis toxin. PMID- 1878228 TI - Ribosomal gene amplification in oocytes of the lizard Podarcis sicula. AB - In order to provide cytological evidence of amplification, Podarcis sicula oocytes were studied by cytophotometry, thymidine incorporation and in situ DNA DNA hybridization. Our results show that DNA replication is completed during the preleptotene stage, the leptotene oocytes having the typical 4C nuclear DNA content. Between the zygotene and the mid-pachytene stages further DNA synthesis occurs with consequent increase of the ribosomal nuclear DNA content. These results and the variations in nucleolar organization observed during differentiation give clear evidence of the existence of ribosomal gene amplification in Podarcis sicula oocytes. PMID- 1878229 TI - Anesthesia at sea: initial experience aboard the hospital ship USNS Comfort during the Iraqi crisis. PMID- 1878230 TI - Anesthesiology in Germany. PMID- 1878231 TI - The effectiveness of oral clonidine as a sedative/anxiolytic and as a drug to blunt the hemodynamic responses to laryngoscopy. AB - STUDY OBJECTIVE: To determine the effects of oral clonidine premedication on sedative, anxiolytic, and hemodynamic responses during the immediate preoperative period, laryngoscopy/intubation, and postanesthetic recovery. DESIGN: Randomized double-blind assignment to one of four treatment groups (clonidine 0.1 mg, clonidine 0.2 mg, triazolam 0.25 mg, or placebo); n = 10 per group. SETTING: Inpatient surgery in a university-staffed tertiary center. PATIENTS: Forty ASA physical status I and II adults of both sexes scheduled for a variety of procedures requiring general anesthesia. INTERVENTIONS: Anxiety and sedation scored on ordinal scale at time of treatment and 90 minutes later, just prior to anesthetic induction. Standardized induction protocol with automated hemodynamic monitoring at 1-minute intervals and a 45-second laryngoscopy to ensure a vigorous stress response. MEASUREMENTS AND MAIN RESULTS: Triazolam and both doses of clonidine increased sedation at 90 minutes both absolutely and compared with a placebo. Clonidine 0.2 mg decreased anxiety absolutely at 90 minutes but no more than a placebo. Clonidine 0.2 mg decreased systolic, mean, and diastolic blood pressures (BPs) but not heart rate (HR) at 90 minutes. Clonidine 0.2 mg also blunted the increase in systolic blood pressure (SP) [but not in diastolic blood pressure (DP) or HR] that accompanied laryngoscopy. There were no treatment differences in postanesthetic hemodynamics or duration of recovery. CONCLUSIONS: Oral clonidine 0.2 mg was effective in reducing the level of behavioral and hemodynamic responses preoperatively and in blunting systolic hypertension produced by prolonged laryngoscopy. PMID- 1878232 TI - Postoperative pain management and respiratory depression after thoracotomy: a comparison of intramuscular piritramide and intravenous patient-controlled analgesia using fentanyl or buprenorphine. AB - STUDY OBJECTIVE: To compare the analgesic efficacy of fentanyl, buprenorphine, and piritramide and to define the respiratory risk during conventional postoperative pain management and patient-controlled analgesia (PCA). DESIGN: Randomized, single-blind study. SETTING: Department of anesthesiology of an urban hospital. PATIENTS: Sixty patients (ASA) physical status II and III) recovering from unilateral thoracotomy performed under standardized general anesthesia including intercostal blockade. INTERVENTIONS: Patients were treated with intramuscular (IM) piritramide (7.5 to 15 mg as needed) or intravenous (IV) PCA with fentanyl (demand dose 34 micrograms) or buprenorphine (demand dose 80 micrograms) during the early postoperative period, using the On-Demand Analgesia Computer (ODAC, Janssen Scientific Instruments, Beerse, Belgium). MEASUREMENTS AND MAIN RESULTS: The mean postoperative observation period was 24 to 25 hours. During this time, patients requested 55.8 +/- 23.2 mg of piritramide, 1.04 +/- 0.54 mg of fentanyl, or 1.81 +/- 0.78 mg of buprenorphine. Analgesia in all groups was judged mostly good to excellent, with a preference for PCA. Side effects were only of minor intensity in all groups; euphoria or dysphoria occurred only with buprenorphine. Two patients using PCA and five patients having IM analgesia developed short periods of respiratory depression (respiratory rate less than or equal to 8 breaths/minute and/or oxygen (O2) desaturation less than or equal to 90%), which promptly responded to commands to breathe deeply. Respiration rates did not differ, and frequent arterial blood sampling showed normal mean partial pressures of oxygen (PO2) and carbon dioxide (PCO2) and arterial oxygen saturation (SaO2) in all subgroups. CONCLUSIONS: Opioid-induced respiratory depression occurred infrequently during postoperative pain management whether by conventional means or using PCA, even though high doses of opioid analgesics were required intermittently for adequate postoperative pain relief by either technique. PMID- 1878234 TI - Trial of labor: a study of 110 patients. AB - STUDY OBJECTIVE: The purpose of the study was to determine whether epidural analgesia is unsafe for trial of labor (TOL). DESIGN: Retrospective chart review. SETTING: Inpatient obstetric department at a university medical center. PATIENTS: One hundred ten ASA physical status I and II term parturients who attempted a TOL between December 1987 and June 1988. INTERVENTIONS: All the parturients previously had low transverse uterine incisions and received continuous electronic fetal and uterine pressure monitoring throughout labor. All the parturients were offered epidural analgesia during labor with bupivacaine 0.25%. MEASUREMENTS AND MAIN RESULTS: Sixty-seven percent of the parturients had successful vaginal delivery. Fifty-one of the 110 parturients had epidural analgesia for labor. There were two complete uterine ruptures; neither had epidural catheters. Both of the complete ruptures presented with monitored fetal distress rather than abdominal pain. Both mothers and their infants recovered uneventfully. CONCLUSIONS: Uterine rupture presents as monitored fetal distress rather than abdominal pain. Thus, epidural analgesia can be used in patients attempting a TOL. PMID- 1878233 TI - Effect of preanesthetic rectal famotidine on pH and volume of gastric contents in pediatric outpatients. AB - STUDY OBJECTIVE: To determine the feasibility and effects of preanesthetic rectal famotidine on gastric fluid pH and volume in pediatric patients. DESIGN: Randomized, prospective, double-blind, controlled study. SETTING: Operating room at a medical center. PATIENTS: Eighty patients undergoing minor surgery under general anesthesia randomly allocated to one of two groups. INTERVENTIONS: Thirty four patients in Group 1 were given 0.5 mg/kg of diazepam rectally 30 to 120 minutes before anesthesia induction. Thirty-eight patients in Group 2 received 1 mg/kg of famotidine, a new histamine (H2) blocker, and 0.5 mg/kg of diazepam through the same route. Six patients in Group 1 and two patients in Group 2 were excluded from the study due to gastrointestinal (GI) disorders. MEASUREMENTS AND MAIN RESULTS: Patients with gastric pH less than 2.5 or volume of gastric contents greater than 0.4 ml/kg were considered to be at risk for pulmonary aspiration. Thirty-five (92%) of the Group 2 patients had gastric contents with pH greater than 2.5 and gastric volume less than or equal to 0.4 ml/kg. Only 13 (38%) of the patients in Group 1 had similar gastric pH and volume. Rectal administration did not cause the children pain, and no anorectal problems of famotidine were detected. CONCLUSIONS: Famotidine 1.0 mg/kg administered rectally 30 minutes prior to general anesthesia appears to result in a satisfactory increase in gastric pH. PMID- 1878236 TI - Atracurium use in a patient with familial periodic paralysis. AB - We describe a patient with the hypokalemic type of familial periodic paralysis (FPP) who received atracurium for muscle relaxation as required for diagnostic laparoscopy. Electrocardiographic (EKG) T-wave changes suggestive of hypokalemia were not supported by blood determinations. Arterial blood measurements of potassium (K+), pH, and arterial carbon dioxide tension (PaCO2) and the patient's esophageal temperature were maintained within normal limits. The degree of muscle relaxation was closely monitored by a peripheral nerve stimulator and train-of four (TOF) measurement of muscle twitch height. At the conclusion of the surgical procedure, no reversal to the muscle relaxant was needed or given. The patient regained preoperative muscle strength, and her postoperative course was uneventful. PMID- 1878235 TI - The clinical effectiveness of epidural bupivacaine, bupivacaine with lidocaine, and bupivacaine with fentanyl for labor analgesia. AB - STUDY OBJECTIVE: To examine the efficacy of bupivacaine alone and in combination with lidocaine or fentanyl for epidural analgesia during labor. DESIGN: Randomized, single-blind study. SETTING: Labor and delivery unit at a university medical center. PATIENTS: Forty-five primiparas requesting epidural analgesia. INTERVENTIONS: Following epidural placement at L3-4 interspace, patients received either bupivacaine 0.5% (Group 1, n = 15), bupivacaine 0.25% with lidocaine 1% (Group 2, n = 15), or bupivacaine 0.5% with fentanyl 50 micrograms in 10 ml of saline (Group 3, n = 15). Patients in Groups 1 and 2 received 6 to 10 ml of local anesthetic depending on patient height, while patients in Group 3 received 5 ml of local anesthetic plus 50 micrograms of fentanyl in 10 ml of saline. All solutions contained epinephrine 1:200,000. MEASUREMENTS AND MAIN RESULTS: Patients were assessed at regular intervals following administration of the epidural solution. Visual analog scale (VAS) scores were used to measure onset of analgesia, time to complete pain relief, duration of analgesia, and patient satisfaction with therapy. The frequency of shivering and pruritus and the extent of sensory/motor block also were evaluated. There were no intragroup differences in time to complete pain relief or patient satisfaction. However, patients in Group 3 noted the most rapid onset and longest duration of pain relief. Patients in Group 3 also experienced significantly less shivering and had the lowest degree of motor block. Two patients in Group 3 experienced mild pruritus. CONCLUSIONS: Epidurally administered fentanyl safely extended the duration of labor analgesia while reducing bupivacaine dose requirements and magnitude of motor block. In this setting, the combination of bupivacaine and lidocaine offered no clinical advantage over bupivacaine alone. PMID- 1878237 TI - Bilateral tension pneumothorax due to a defective anesthesia breathing circuit filter. AB - A 25-year-old healthy patient developed bilateral tension pneumothorax during general endotracheal anesthesia due to a defective anesthesia breathing circuit filter. Prompt diagnosis and treatment of the pneumothorax was facilitated by the use of capnography and pulse oximetry. The manufacturing process of the breathing circuit and filter that made this accident possible has since been corrected by the manufacturer. Anesthesiologists must be alert to the possibility of such accidents with any breathing system using bacterial filters. PMID- 1878238 TI - History of anesthesia in Germany. AB - The first ether anesthetic was administered in Germany by J.F. Heyfelder (1798 1869) at the Erlangen University Hospital on January 24, 1847. Thereafter, famous discoveries occurred in the field of pharmacology. Albert Niemann isolated cocaine from the coca shrub in 1860; Emil Fischer synthesized the first barbiturate, Veronal, in 1902; and Helmut Weese promoted the first ultra-short acting barbiturate, hexobarbital (Evipan), in 1932. The local anesthetic effect of cocaine was reported by Koller at the Congress of the German Society for Ophthalmology on September 15, 1884, in Heidelberg. Many new techniques were tried first in German hospitals. Friedrich Trendelenburg carried out, by tracheotomy, the first operation with endotracheal intubation in 1869, and Franz Kuhn promoted and clinically practiced endotracheal intubation in Heidelberg beginning in 1900. August Bier performed the first operation under spinal anesthesia at the Kiel University Hospital on August 16, 1898. Carl Ludwig Schleich (1859-1922) standardized the methods of infiltration anesthesia by using a cocaine solution in sufficient dilution. The development of anesthesia machines was greatly influenced by Heinrich Drager (1847-1917) and his son Bernhard Drager (1870-1928). The Drager Company in Lubeck built the first anesthesia machine with a carbon dioxide (CO2) absorber and circle system in 1925. Paul Sudeck and Helmut Schmidt worked with this system at the Hamburg University Hospital and reported their results in 1926. The first Drager anesthesia machine was produced in 1902 and introduced into clinical use by Otto Roth (1863-1944) in Lubeck. Before the Second World War, three universities in Germany carried out research in the field of anesthesia: the University of Freiburg with H. Killian, the University of Hamburg with P. Sudeck and H. Schmidt, and the University of Wurzburg with C.G. Gauss. Killian and Gauss established the first journals, Der Schmerz and Narkose und Anaesthesie, in 1928. After the Second World War, the field of anesthesia in Germany rapidly regained international standards. The journal Der Anaesthesist was founded in 1952, and the German Society for Anesthesiology and Intensive Medicine was established in 1953. PMID- 1878239 TI - History of emergency medicine in Germany. AB - The beginnings of organized emergency care can be traced through military history dating back to the Middle Ages. In 1769, the first civilian rescue society was established to look after shipwrecked persons. Sociological and technical requirements of the late 19th century led to the formation of different rescue associations and to writing of regulations for rescue and ambulance services. The development of quality assurance was interrupted by World War I. Around 1930, the rescue service was mostly the responsibility of the Red Cross and fire brigades but included the first actions of emergency physicians. Today the rescue service functions to bring a physician, often an anesthesiologist, to the victim as quickly as possible. Modern rescue laws fix a lead time of 5 to 15 minutes for a professional rescue service to reach the scene. The medical equipment and qualifications of personnel treating life-threatening trauma and diseases have improved, and in this context, the role of the anesthesiologist is important. PMID- 1878240 TI - Anesthesia training in West Germany. AB - The specialty of anesthesia was established in German medicine in 1953 with the founding of the Germany Society of Anaesthesia and the inclusion of a "specialist in anesthesia" as part of the German medical training requirements. Anesthesia training is offered to students and residents and as a part of continuing education. A residency training program lasts at least 4 years, including 6 months of intensive care unit (ICU) training, and ends with an oral examination. About 900 anesthesia departments in West Germany are accredited for residency training programs. Of those, about 320 are fully accredited. Continuing education in West German anesthesia is very similar to that offered in the United States. PMID- 1878241 TI - Development of intensive care medicine in Germany. AB - As of 1991, intensive care medicine in Germany is not an independent medical specialty but a part of other main medical specialities such as anesthesiology, internal medicine, surgery, and pediatrics. Accordingly, there is neither formal training nor a separate board examination in intensive care medicine. As in other countries, intensive care units (ICUs) were established during the 1950s and 1960s, triggered by the positive experience with consolidation of polio victims in special respiratory care units. Surgical (or operative) ICUs predominantly are operated by anesthesiology departments, as anesthesiologists' expertise in respiratory and hemodynamic support qualifies them for the management of the critically ill patient in the perioperative phase. This article gives a brief review of the development of intensive care medicine in Germany, thereby providing the historical background for its present national and regional organization, facilities, and education and training programs. PMID- 1878242 TI - Medical equipment ordinance and lack of personnel: two contrary factors influencing anesthesia patient safety. AB - In January 1986, West German legislators enacted the Medical Equipment Ordinance (MedGV) to define specific regulations for both manufacturers and operators of medical equipment and to offer a measure of safety to patients. We describe the history of MedGV, its regulations, and the mechanisms developed to enforce those regulations. We also evaluate its impact on clinical practice in light of the current staff shortages in anesthesia practice and research in Germany. Finally, we focus our discussion on the distinction between improved equipment as a minor factor in critical-incidents and the inadequate manpower as a major factor in anesthesia mishaps. It is unclear what will develop after 1993, when the national states in Europe form a common market. PMID- 1878243 TI - Citropten and bergapten suction blister fluid concentrations after solar product application in man. AB - Citropten (5,7-dimethoxycoumarin) and bergapten (5-methoxypsoralen) are present in bergamot oil which is used as a cosmetic tanning product. The aim of this study was to quantify, using HPLC, the amount of citropten and bergapten in the skin after the application of suntan products (emulsion and oil formulations). A suction blister technique, performed on the volar aspect of the forearm, permitted the collection of these two molecules. The blister fluid concentrations were 37 and 51 ng/ml (emulsion) and 26 and 23 ng/ml (oil), respectively, for citropten and bergapten. Our results show that the suction blister technique could be used for comparing transepidermal penetration of several compounds in vivo in man. PMID- 1878244 TI - Efficacy of topical dimetindene in experimentally induced pruritus and weal and flare reactions. AB - Double-blind, placebo-controlled studies were performed to assess the effect of 0.1% dimetindene gel on the itch threshold to intracutaneous histamine and on the weal and flare reaction after intracutaneous injection of histamine in normal volunteer subjects. Treatment of the forearm skin in 20 volunteers resulted in an increase in itch threshold with dimetindene gel compared to placebo. Treatment of the forearm skin with dimetindene gel in 32 volunteers had no significant effect on weal thickness in subjects treated for 10, 30 or 60 min, but there was a significant reduction in weal thickness in those subjects treated for 120 min. Topical dimetindene may be of value in treating conditions mediated through histamine release. PMID- 1878245 TI - Automatic scanner for multi-point laser Doppler flux recordings on human skin. AB - A computer-driven device is described which moves the probes of a laser Doppler flowmeter linearly back and forth over the skin and stops precisely at preselected points to measure capillary perfusion. It offers extended possibilities to record the spatio-temporal flux changes in response to a local stimulus (e.g. injection of a vasoactive substance). PMID- 1878246 TI - Transforming growth factor alpha: in vivo release by normal human skin following UV irradiation and abrasion. AB - Transforming growth factor alpha (TGF alpha) is a keratinocyte-growth-stimulating factor which may have a role in epidermal hyperproliferation, psoriasis, and wound healing. Since increased epidermal proliferation occurs in response to UV radiation, we have measured the amount of TGF alpha in exudates from normal and UVB-irradiated human skin. Cutaneous exudates were obtained using the skin chamber abrasion technique from one side of the back of volunteers (n = 10) with normal skin (collected following skin contact times of 2 and 30 min). Exudates were similarly obtained from the contralateral side of the back at sites irradiated 2 h previously with 3 x the minimum erythemal dose UVB. Levels of TGF alpha were measured by radioimmunoassay. Normal human skin released TGF alpha immediately after abrasion: unirradiated, 63 +/- 18 ng/ml; irradiated, 89 +/- 15 ng/ml. Levels of TGF alpha increased within 30 min to 110 +/- 14 ng/ml in unirradiated skin and to 190 +/- 17 ng/ml in irradiated skin. Irradiated sites at 30-min time points were significantly higher (p less than 0.05) than all other samples. The presence of releasable TGF alpha in normal skin suggests a role for TGF alpha in wound repair mechanisms. PMID- 1878247 TI - Transepidermal water loss modifications in rats and humans treated with cyclosporin. AB - Modifications of transepidermal water loss (TEWL) of rat and human skin induced by oral administration of cyclosporin (CS) were investigated. The integrity of the cutaneous barrier was evaluated using TEWL measurement which is a relatively simple and noninvasive means of assessing the functional state of the cutaneous barrier. After 12 weeks, the TEWL of treated rats decreased significantly and this difference was still present after the 16 weeks of treatment. In humans, there was a statistically significant decrease of TEWL on both forearm and thigh in CS-treated patients compared to non-CS-treated patients and controls (p less than 0.05). These results suggest that CS causes skin modifications, particularly concerning its barrier status. The nature of these skin modifications still remains to be determined. PMID- 1878248 TI - Ciclopiroxolamine cream 1%: in vitro and in vivo penetration into the stratum corneum. AB - Studies were conducted to assess the penetration of 1% ciclopiroxolamine cream, establishing the concentrations of the antimycotic compound in different layers of the stratum corneum with two skin models. Results of in vitro studies using skin from domestic pigs indicate that ciclopiroxolamine has the ability to penetrate fast into the epidermis, by inhibiting and killing inoculated Trichophyton mentagrophytes. In vivo investigation of the stratum corneum has been performed in healthy human volunteers by 20 strippings collected in four layers. Fungicidal concentrations of ciclopiroxolamine were determined after extraction from the strippings. These studies demonstrate that the concentrations reached levels which are sufficient to inhibit and kill pathogenic fungi. PMID- 1878249 TI - One gene encoding three proteins with different functions. PMID- 1878251 TI - Surfactant proteins and SP-D. PMID- 1878250 TI - Developmental expression of pulmonary surfactant protein D (SP-D). AB - Surfactant protein D (SP-D) is a collagenous, surfactant-associated, carbohydrate binding protein that is synthesized by pulmonary epithelial cells. In the present studies, we examined the expression of SP-D and SP-D mRNA during late fetal (day 17, 19, 21) and early postnatal (day 5) rat lung development using immunochemical, cell-free translation, and Northern hybridization assays. SP-D mRNA and immunoreactive SP-D protein were first detected in guanidine extracts of whole rat lung at 21 days of gestation and reached even higher concentrations during the postnatal period. Likewise, immunoperoxidase studies of rat lung using affinity-purified antibodies to SP-D showed no staining at day 17 or 19, but demonstrated strong cytoplasmic staining of cuboidal epithelial cells lining immature airspaces at day 21 and strong cytoplasmic staining of type II and nonciliated bronchiolar cells in adult lung. SP-D also appeared in amniotic fluid by day 21 and was partially purified by affinity chromatography on maltosyl agarose under conditions used for the isolation of rat lung SP-D. These studies indicate that the production of SP-D is increased shortly prior to birth, and that the increases in total lung SP-D and SP-D mRNA are temporally correlated with SP-D secretion and the appearance of SP-D in amniotic fluid. PMID- 1878252 TI - Changes in lipid structure produced by surfactant proteins SP-A, SP-B, and SP-C. AB - Pulmonary surfactant phospholipids may assume several different structures including tubular myelin, unilamellar and multilamellar vesicles, and others. These populations of materials appear to have similar phospholipid compositions but may differ in their association with surfactant proteins SP-A, SP-B, or SP-C. We have used electron microscopy to determine the changes in structure of simple lipid mixtures (phosphatidylglycerol, dipalmitoylphosphatidylcholine) produced by adding one or combinations of the three proteins. Adding SP-A to lipids generated multilamellar structures composed of membranes with fuzzy or particulate surfaces. In contrast, SP-B or SP-C generated discoidal particles and structures that appeared to be sheets of membrane formed by associated particles. Used together, SP-A and SP-B reorganized some of the lipid into tubular myelin, a structure that was not observed in SP-A, SP-C recombinants. These observations confirm the in vitro formation of tubular myelin reported by others and support the possibility that surfactant materials with defined structure can be produced in vitro for analyses of their molecular organizations. PMID- 1878253 TI - In vivo regulation of surfactant proteins by glucocorticoids. AB - Surfactant proteins have key roles in regulating surfactant secretion, in recycling, and in the assembly of the surfactant monolayer but little is known about their regulation in vivo. Surfactant proteins SP-A, SP-B, and SP-C have been shown to be upregulated by glucocorticoids in vitro, but the role of glucocorticoids in the physiologic regulation of surfactant protein synthesis remains unknown. We have studied the effects of exogenously administered glucocorticoids on the regulation of steady-state surfactant protein mRNA accumulation. We have also studied the effects of adrenalectomy on the accumulation of the surfactant protein mRNAs. Surfactant protein genes appear to have quantitatively different responses to exogenously administered glucocorticoids, with SP-C mRNA increasing at the lowest dose, SP-A and SP-B mRNA increasing in response to similar glucocorticoids doses but with SP-B yielding the highest maximum response. Adrenalectomy, however, does not alter surfactant protein mRNA levels. These observations support a minor role for glucocorticoids in maintaining the steady-state accumulation of surfactant protein mRNA. Adrenalectomy decreases total pulmonary SP-A when compared to sham-operated animals in the absence of changes in its mRNA. Therefore, glucocorticoids may have translational or post-translational effects that regulate total pulmonary SP A accumulation, but the effects appear to be minor. These findings support a potential role for the adrenal in the pulmonary response to stress and demonstrate for the first time differential accumulation of the surfactant protein mRNAs to glucocorticoids in vivo. PMID- 1878254 TI - Use of a monoclonal antibody enzyme-linked immunosorbent assay to measure human respiratory glycoprotein production in vitro. AB - High-molecular-weight glycoprotein from human airway cultures was used to generate murine monoclonal antibodies, one of which recognizes a high-molecular weight, hyaluronidase-resistant glycoprotein localized by immunofluorescent microscopy and immunogold electron microscopy to the secretory granules of human airway submucosal gland mucous cells and goblet cells. This monoclonal antibody was used to develop an enzyme-linked immunosorbent assay (ELISA) that was adapted to the study of respiratory glycoprotein secretion from human airways in vitro. Using the assay, the effect of a known mucus secretagogue, the cholinergic agonist methacholine, was studied on explant cultures of tissue from human bronchus or from human nasal mucosa. In studies of human bronchus explants, methacholine, 100 and 10 microM, stimulated increased secretion of respiratory glycoprotein (RGP) by 109 +/- 8% (n = 14; P less than 0.001) and 96 +/- 14% (n = 9; P less than 0.001), respectively, above control values. In studies of human nasal turbinate mucosal explants, methacholine, 100 and 10 microM, stimulated increased secretion of RGP by 75 +/- 28% (n = 7; P less than 0.01) and 70 +/- 21% (n = 4; P less than 0.01) above control values. An ELISA for the measurement of RGP secretion may provide a sensitive and more specific method for the performance of in vitro studies of RGP secretion from human tissues. PMID- 1878255 TI - Temporal segregation of surfactant secretion and lamellar body biogenesis in primary cultures of rat alveolar type II cells. AB - Pulmonary alveolar type II cells synthesize and secrete the phospholipids of surfactant. However, type II cells isolated from adult rat lungs rapidly lose their characteristic morphology and differentiated functions (such as surfactant specific phospholipid and protein biosynthesis) when maintained on tissue culture plastic. In this study, phospholipid secretion and its regulation by type II cells grown on tissue culture plastic were examined up to 8 days after isolation. Type II cells were preincubated with [3H]choline for varying 24-h periods during culture prior to examining phosphatidylcholine ([3H]PtdCho) secretion. Type II cells cultured for 4 days and incubated with [3H]choline 24 h before the secretion experiment failed to show significant basal and tetradecanoyl phorbol acetate (TPA, 100 nM)-stimulated [3H]PtdCho secretion (basal, 0.29 +/- 0.01%; TPA, 0.48 +/- 0.04%). In contrast, type II cells incubated with [3H]choline for the first 24 h during culture and then cultured for 3 more days showed significant [3H]PtdCho secretion (basal, 1.27 +/- 0.19%; TPA, 6.24 +/- 0.82%). Subcellular fractionation of type II cells revealed that [3H]choline was incorporated into phosphatidylcholines in a lamellar body-enriched fraction during the first 24 h of culture but that the assimilation of phosphatidylcholine into the lamellar body fraction progressively declined with increasing time in culture. Radiolabel incorporated into the lamellar body fraction labeled during the first 24 h of culture was detectable for up to 8 days in culture. The [3H]PtdCho incorporated into the lamellar body during the first 24 h of culture was lost gradually over 8 days, suggesting the continuous secretion or turnover of the lamellar bodies during culture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878256 TI - Release of tumor necrosis factor in guinea pigs upon acute inhalation of cotton dust. AB - In guinea pigs, inhalation of cotton dust results in an acute pulmonary response with symptoms of increased breathing rate, cough, bronchoconstriction, and periods of apnea. These symptoms resemble those noted in individuals upon exposure to cotton and other organic dusts. A major contaminant of cotton dust is bacterial endotoxin. Because endotoxin, or lipopolysaccharide, is recognized to be a potent stimulator of tumor necrosis factor (TNF), it was postulated that TNF might be released in the lung following cotton dust exposure and associated with the pulmonary inflammatory response. Groups of guinea pigs were exposed to an atmosphere of 33 mg/m3 cotton dust for up to 6 h. At 3, 6, 7.5, and 24 h, lungs were isolated and lavaged to assess cell populations and production of TNF. Neutrophil infiltration was apparent by 3 h as was a marked increase in TNF in bronchial alveolar lavage fluid. Alveolar macrophages (AM) isolated at 3 h showed enhanced release of TNF upon in vitro culture when compared with those isolated at the other time points. AM were found to be primed to release TNF upon ex vivo stimulation with lipopolysaccharide. The greatest effect was noted with AM isolated 1.5 h after the 6-h cotton dust exposure. These results demonstrate the ability of cotton dust to cause release of TNF in the lung and suggest a role for TNF in the inflammatory response to cotton dust. PMID- 1878257 TI - Staphylococcal enterotoxins and the immune system. PMID- 1878258 TI - The effect of Mycoplasma arthritidis infection on the phagocytic activity of macrophages in rats and mice. AB - The phagocytic activity of mononuclear phagocytes of A/J mice and Wistar rats was estimated by the carbon clearance test following injection of Mycoplasma arthritidis. In mice, the overall phagocytic activity was significantly increased at the end of the first week (P less than 0.0001), but the increase was marginal by the third and fourth weeks after injection. A significant increase in the relative weight of liver and spleen was observed even when phagocytic activity had returned to levels similar to those of controls (P less than 0.001). In rats, the overall phagocytic activity was significantly increased until the fourth week (P less than 0.00001). There was not, however, an increase in the relative weight of liver and spleen as observed for the mice. The results are discussed in the context of factors contributing to the pathogenic mechanisms responsible for differences in the patterns of arthritis due to mycoplasma observed in mice and rats. PMID- 1878260 TI - Neonatal tetanus despite protective serum antitoxin concentration. AB - Using the ELISA technique to estimate serum antibodies against tetanus toxin, seven neonates with clinical tetanus were found to have antibody levels 4-13 times higher than the presumed minimum protective level of 0.01 IU/ml. All but one of their mothers had been vaccinated with tetanus toxoid in pregnancy. In two other neonates, whose mothers had received multiple booster doses of toxoid during pregnancy, the anti-toxin concentrations were 100- and 400-times the presumed protective level. Therefore the toxin dose may overwhelm the pre existing anti-toxin level and produce disease. Furthermore, multiple booster injections of tetanus toxoid may not only enhance serum anti-toxin titres, but could also lead to an ineffective immune response. PMID- 1878259 TI - Potentials of Shigella flexneri Y strain TSF21 as a candidate vaccine against shigellosis: safety, immunogenicity and protective efficacy in Bonnet monkeys. AB - A thymine-requiring and temperature-sensitive mutant of Shigella flexneri Y was tested in Bonnet monkeys for safety, immunogenicity and protective efficacy. A dose of 10(11) cells when fed orally mimicked natural infection in having invaded epithelial cells, but was otherwise clinically non-reactogenic. Animals immunized with two oral doses, each dose consisting of 1 x 10(11) mutant bacteria, were fully protected when challenged, with respect to the lack of any clinical symptoms or detectable histological abnormalities in the intestinal mucosa. Unimmunized animals when similarly challenged developed frank dysentery and the intestinal mucosa showed severe histological abnormalities. Titres of serum antibodies increased by about 11-fold of the base level in animals immunized with a dose of 10(11) cells, but not with lower doses. The challenge bacteria appeared to be phagocytised by macrophages. In some monkeys of a particular group, congestive patches were seen in the stomach, but not in any other part of the gut, after the animals were fed with the virulent parent strain. The lesions were relatively severe in the immunized groups of animals. PMID- 1878261 TI - Genetic analysis of the polymorphism of the human apolipoprotein E using automated solid-phase sequencing. AB - A direct sequencing approach has been used to analyze the polymorphism in the human apolipoprotein E gene. A method is described, in which the DNA is amplified by the polymerase chain reaction, immobilized, and sequenced by a semi-automatic procedure adaptable to clinical diagnosis. The three alleles of the apolipoprotein E gene, which differ from each other by two nucleotide substitutions and which influence serum cholesterol levels, were analyzed. The solid-phase method was able to resolve the correct nucleotide sequence in samples from both homozygous and heterozygous individuals. No cloning steps are needed and the immobilization and separation of the DNA is accomplished using magnetic beads. PMID- 1878262 TI - A simple, effective method for the construction of subtracted cDNA libraries. AB - A simple method is described for the construction of subtracted cDNA libraries. The technique was used to create a human pancreatic tumor cDNA library that was screened using either hybridization with cDNA probes or antibodies. cDNA from a well-differentiated tumor cell line (CD-11) was subtracted against RNA from an undifferentiated tumor cell line (Panc-1). The subtracted cDNA was purified from RNA-cDNA hybrids by oligo-dA cellulose affinity chromatography. Single-stranded subtracted cDNA was used as a template for random primed second-strand synthesis using the Klenow's fragment of DNA polymerase. After ligation with Eco R1 adapters, cDNA was inserted into lambda gt11. A library of 140,000 primary pfu was obtained that contained 92% recombinants. A small portion of this library (40,000 pfu) was subjected to probe screening with a mucin cDNA probe known to be differentially expressed by CD-11 cells. The ratio of mucin cDNA clones to actin cDNA clones was increased by greater than 300-fold in the subtracted cDNA library compared to a standard cDNA library from the same cell line. The absolute number of mucin cDNA clones per 40,000 pfu was also increased 32-fold in the subtracted library. Pancreatic tumor mucin cDNAs were also identified in the subtracted library by antibody screening. The subtraction procedure yielded a 50-fold enrichment in differentially expressed cDNA detected by antibodies, compared to a nonsubtracted library from the same cell line. PMID- 1878263 TI - A test of human cDNA synthesis by the polymerase chain reaction. AB - A fast and efficient method to test the quality of human cDNA synthesis based on the polymerase chain reaction (PCR) is described. An aliquot of the cDNA reaction is used as a template for PCR amplification of a segment of the human histidyl tRNA synthetase gene. The presence of an intron of approximately 300 bp in that region of the gene permits the identification of any genomic contamination in the cDNA sample. The same protocol has also been used with other mammalian DNAs with similar results. PMID- 1878264 TI - Moving forward on research. PMID- 1878265 TI - Statistics--with confidence? PMID- 1878266 TI - Good general practice--fellowship of the RCGP by assessment. PMID- 1878267 TI - Longer booking intervals in general practice: effects on doctors' stress and arousal. AB - A controlled trial was carried out to determine whether longer booking intervals at surgeries affected general practitioners' self-assessed levels of stress and arousal. Sixteen general practitioners from 10 practices took part. Surgery sessions with patients booked at 10 minute intervals (experimental sessions) were compared with the doctors' usual booking intervals of between 7.5 and 5.0 minutes (control sessions). Stress and arousal were assessed by the general practitioner before and after each surgery session using a mood adjective check list. The study included 109 experimental and 184 control sessions. The median consultation length increased from six minutes in the control sessions to seven minutes in the experimental sessions. At the end of the experimental sessions, stress scores were lower, and arousal scores higher than at the end of the control sessions (P less than 0.001). There were no significant differences between experimental and control sessions in stress or arousal at the start of the sessions. Favourable mood changes were seen more consistently in the experimental sessions than control sessions, with less than a quarter of doctors showing increased stress or decreased arousal after sessions relative to before. It is concluded that longer booking intervals are of psychological advantage to general practitioners. PMID- 1878268 TI - The potential and limitations of opportunistic screening: data from a computer simulation of a general practice screening programme. AB - Given the continuing emphasis on preventive medicine in general practice, there is considerable interest in the relative effectiveness of different ways of inviting patients to attend for screening. Recently, opportunistic methods have been advocated as being particularly useful but these methods often fail to reach a high proportion of the target population. Many patients do not consult and when they do they are not always invited to attend for screening. In this study a computer simulation model has been used to examine the effects of these variables in more detail. The notes of a random sample of 190 patients (97 women, 93 men) aged 30-50 years, registered with one general practitioner, were used to provide data for the model. The simulation model showed that increasing the number of screening appointments available each week has only a small effect on screening rates and that a ceiling is reached when 25 appointments per 1000 patients are available. In contrast, increasing the proportion of eligible consulting patients who are invited has a substantial effect such that it could take nearly 12 years to screen 90% of a target population if only one out of every four patients were invited compared with under four years if three out of every four patients were invited. The results suggest therefore that opportunistic screening methods are unlikely to achieve desired screening rates within acceptable time limits. It is argued that to achieve target levels of screening, practices will need to combine opportunistic methods with more formal methods of invitation. PMID- 1878269 TI - Determinants of forearm bone density in premenopausal women: a study in one general practice. AB - Predictors of distal and proximal forearm bone density, measured by photon absorbtiometry, were investigated in 248 premenopausal women aged 39-56 years. Only one strong predictor of lower bone density was found--history of previous fracture at any site (P less than 0.001). Two other factors showed a weaker association with density, but only at the distal site--history of diuretic use showed a positive association (P less than 0.02) whereas alkaline phosphatase level was inversely correlated with density (P less than 0.01). Other factors were not significant predictors: these included age, calcium intake, level of exercise, anthropometric measures of obesity, serum calcium level, parity, lactation history, a menopausal symptom history, use of the contraceptive pill, smoking and alcohol intake. These results contrast with the far stronger predictors found for postmenopausal women and suggest that genetic endowment rather than lifestyle may be the major determinant of bone density before the menopause. PMID- 1878270 TI - Patient participation in general practice: who participates? AB - A postal survey of 4066 men and women aged between 16 and 64 years was carried out in a general practice in Oxfordshire which had a patient participation group, established in 1972. The aim of the survey was to ascertain the knowledge and use of the group among adults aged 16-64 years. The adjusted response rate was 73%. Despite the length of the group's existence only 45% of these patients were aware of it and only 7% had ever attended a meeting. Awareness of the group and sometime attendance were significantly less in men, patients aged between 16 and 29 years, those in social classes 4 and 5, single people and those who smoked. Patients who consulted more than four times per year were more likely to be aware of the group than less frequent consulters. The possible reasons for the unrepresentative nature of the patients attending the group are discussed, together with implications for practice policies and development. Various strategies for making the group more representative are proposed, including advertising within the practice and elsewhere, and the formation of special interest groups for patients with defined medical and social needs, in the hope that this will make the concept of patient participation more relevant. PMID- 1878271 TI - Changes in practice morbidity between the 1970 and 1981 national morbidity surveys. AB - The primary aim of the study was to evaluate practice differences in reported morbidity in the second and third national morbidity surveys (1970/71, 1981/82) and to discuss their cause. A secondary aim concerned the validation of trends identified from analysis of the data from the total populations in the practices. Altogether 19 practices participated in both surveys. Annual prevalences (that is, the number of patients attending the general practitioner with a condition per 1000 persons at risk) were examined for: all conditions; each of three categories of seriousness of disease; diseases aggregated by chapter of the International classification of diseases; and each of 130 rubrics of the disease classification. Annual prevalence for 'all conditions' was approximately the same for males in both surveys, whereas for females there was an increase. In both sexes, annual prevalence for 'serious conditions' increased slightly and for 'trivial conditions' increased substantially. For 'intermediate conditions', there was a modest decrease in males. In the analysis at ICD chapter level, substantial increases in prevalence occurred in infectious diseases, nervous system diseases, circulatory diseases, genitourinary diseases, musculoskeletal diseases, symptoms, signs and ill-defined conditions, injuries and poisonings. Decreases were found in blood diseases, mental disorders and digestive diseases. Among 130 individual conditions examined, increased annual prevalence was found for mumps, fungal infections, hypothyroidism, diabetes, gout, senile dementia, angina, left heart failure, catarrh, hay fever and asthma, orchitis, acne, osteoarthritis and for some symptoms. Decreases were found for iron deficiency anaemia, anxiety state, refractive errors, haemorrhoids, chronic bronchitis, functional disorders of the stomach, carbuncle and skin infections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878272 TI - Patients' views of the consultation: comparison of a prison and general practice population. AB - Prisoners' perceptions of why they consulted the doctor, how ill they thought they were and what happened during the consultation were studied in Bedford prison using a questionnaire. Patients' perceptions were compared before and after the consultation and with the perception of the doctor. The figures from this study were compared with comparable groups in a similar general practice survey. Prisoners perceived themselves to be more ill than comparable groups living in the community and both doctor and prisoners perceived that the prisoners received less reassurance. Prisoners were less likely to attend the doctor because their treatment had not worked, or because the doctor had asked them to return than comparable groups living in the community. The perception of the doctor and the prisoners about what occurred in the consultation diverged. The doctors perceived that they provided more advice and support than the prisoners felt they received. These perceptions may reflect a more difficult doctor-patient relationship and poorer continuity of care in prison medicine. These problems might be overcome if the prison medical service were run by the National Health Service and prison doctors had no role in the management of prisoners. PMID- 1878274 TI - Treatment of skin cancers in general practice. PMID- 1878273 TI - Out of hours attendance in an army practice. AB - There is some evidence that rates of out of hours calls in army general practices are higher than the average for the NHS. In an attempt to reduce out of hours demand a programme of preventive and educational initiatives for patients was introduced at an army practice in Hohne, West Germany early in 1985. This included regular child development clinics, well woman clinics, a practice booklet and leaflets about the management of simple illnesses, a library of books and videos for patients and health education videos in the waiting room. The project was complemented by an audit of doctors' prescribing habits followed by drawing up agreed protocols for the treatment of common disorders such as sore throat. Annual attendance rates per registered patient were recorded for 1984-86 to compare use of out of hours services by patients before and after the introduction of the project. Out of hours attendance rates fell by 35% (from 0.17 per annum to 0.11 per annum) overall and by 61% in young children. The total annual attendance rate dropped by 14% (from 5.13 to 4.43) during the same period, but fell by only 1% over the same period at a similar practice in Osnabruck. The decrease was particularly marked for out of hours attendances which the doctor classified as lower urgency: attendances classed as very low urgency decreased by 78% between 1984 and 1986 but those classed as medium urgency decreased by only 2%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878275 TI - General practitioners' opinions of hospice care. PMID- 1878277 TI - Screening for glaucoma in general practice. PMID- 1878276 TI - Ultrasound in the diagnosis of symptomatic breast disease. PMID- 1878279 TI - The family history and the family doctor. PMID- 1878278 TI - Calculation of the underprivileged area score. PMID- 1878280 TI - Silver tolerance and accumulation in yeasts. AB - Debaryomyces hansenii (NCYC 459 and strain 75-21), Candida albicans (3153A), Saccharomyces cerevisiae (X2180-1B), Rhodotorula rubra (NCYC 797) and Aureobasidium pullulans (IMI 45533 and ATCC 42371) were grown on solid medium supplemented with varying concentrations of AgNO3. Although Ag+ is highly toxic towards yeasts, growth on solid media was still possible at Ag concentrations of 1-2 mM. Further subculture on higher Ag concentrations (up to 5 mM) resulted in elevated tolerance. The extent of Ag tolerance depended on whether Ag-containing plates were exposed to light prior to inoculation since light-mediated reduction of Ag+ to Ag0 resulted in the production of a less toxic silver species. Experimental organisms exhibited blackening of colonies and the surrounding agar during growth on AgNO3-containing medium especially at the highest Ag concentrations tested. All organisms accumulated Ag from the medium; electron microscopy revealed that silver was deposited as electron-dense granules in and around cell walls and in the external medium. X-ray microprobe analysis indicated that these granules were metallic Ag0 although AgCl was also present in some organisms. Volatile and non-volatile reducing compounds were produced by several test organisms which presumably effected Ag+ reduction to Ag0. PMID- 1878281 TI - Reduced hepatic iron uptake from rat aglycotransferrin. AB - Rat aglycotransferrin (rAgTf) was produced from the disialosyl diantennary fraction of rat transferrin (rTf) by treatment with peptide: N-glycosidase F. Following removal of the enzyme by gel filtration and isolation of the deglycosylated protein by lectin chromatography, rAgTf was compared to rTf both in vitro and in vivo. No significant differences were found between the two proteins with respect to affinity for iron and kinetics of Fe release from the N lobe and C-lobe. The fluorescence emission spectrum of apo-rTf was red-shifted by approximately 3 nm relative to diferric rTf; however, no spectral difference was detected between rTf and rAgTf when the analogous forms (apo or diferric) were compared. Plasma clearance of radioactive iron administered to rats as either rTf or rAgTf was comparable. Reticulocytes took up iron from rAgTf slightly faster than from rTf. In contrast, Fe acquisition by the liver from rAgTf was significantly reduced relative to rTf. This finding contrasts sharply with earlier observations with asialotransferrin (rAsTf) and provides a basis for discounting charge loss as the mechanism of enhanced hepatic Fe uptake from rAsTf. It is suggested that the glycan complement of rTf, while unimportant for interaction of the protein with specific receptors, probably plays a role in the interaction with low-affinity hepatic binding sites. PMID- 1878282 TI - The location of exon boundaries in the multimeric iron-storage protein ferritin. AB - The nature of the amino acids whose codons border introns in ferritin genes is novel; the disposition of these intron boundaries within the three-dimensional structure of the 24-subunit molecule differs significantly from that of other proteins. These observations are discussed in relation to the functions of isoferritins. PMID- 1878283 TI - The cortical potential related to sensory feedback from voluntary movements shows somatotopic organization of the supplementary motor area. AB - In topographic EEG mapping, the peak negativity of movement-related cortical potentials (MRCPs) occurs after the onset of movement and appears anterior to motor cortex, over the region of the supplementary motor area (SMA). This peak, referred to as the frontal peak of the motor potential (fpMP), may well be related to sensory feedback from the movement. The somatotopic organization of the SMA is such that the upper extremity is anterior to the lower extremity. We mapped the MRCPs close to the onset of EMG activity relating to finger and toe movements. The fpMP of finger movements mapped more anteriorly than that of toe movements. These maps offer additional evidence that fpMP originates in the SMA. PMID- 1878284 TI - Quantitative representation of the upper surface of the human head. AB - A three dimensional digitizer was used to locate 62 positions on an electrode cap placed on the heads of nine subjects. Nonlinear regression methods were used to obtain the best fit sphere, ellipsoid, and perturbed ellipsoid. RMS errors varied from approximately 1 cm to 2 mm, depending on subject and surface chosen. The spherical coordinates of the standard 10/20 electrodes on best fit spheres were obtained. A method to estimate ellipsoid axes using only three standard EEG head dimensions with an ordinary tape measure is derived from the data. The results have at least two potential applications: the forward/inverse problem in EEG and MEG, and the estimation of surface Laplacians from EEG data. PMID- 1878285 TI - Partitioning of deep versus superficial intracranial sources using current source densities is not valid. AB - An analytic method has recently been proposed for partitioning scalp-recorded EEG and evoked potential (EP) data into parts arising from deep (i.e., subcortical) vs. superficial (i.e., cortical) sources. The method is based on the observation that the current source density (CSD) is selectively sensitive to electrical activity arising from superficial sources, and the conjecture that the residual potential which remains after subtracting the CSD from the scalp potentials, represents activity from deep sources. We investigated the validity of this procedure by simulating scalp potential data for superficial and deep dipole sources with known locations and orientations. Our single-dipole simulations demonstrated that, when the actual location of the source was superficial, the partitioning procedure erroneously attributed a sizeable proportion of the total topographic variance to the activity of deeper sources. This produced a consistent bias in the simulations with two dipoles, when both superficial and deep sources were present. In such cases, the relative contribution of the deeper source was consistently overestimated, and the scalp topography of the deep source activity was profoundly misrepresented by the residual which results from subtracting the CSD from the scalp potential. We conclude that the proposed method for partitioning EEG and EP data into components arising from deep vs. superficial intracranial sources is not valid. PMID- 1878286 TI - EEG laterality in the era of structural brain imaging. AB - Bilateral EEG recording is a common practice when brain laterality needs to be assessed in cognitive neurophysiology and psychiatry research. Its precision and validity remain uncertain. With structural brain imaging methods, it is possible to examine EEG electrode placements according to the 10-20 system and the validity of inferences made on derived data. Frequent sources of placement errors are examined along with important factors that contribute to EEG imbalance. Examples are mentioned where asymmetries of EEG/ERP caused by cranial and parenchymal brain asymmetries may be mistaken for cognition-related laterality changes. Because external skull landmarks are not reliable predictors of cranial and parenchymal brain asymmetries, laterality assessment cannot be guaranteed by the 10-20 system. Consequently, a return, on a case-to-case basis, to nonstandard montages, assisted by structural brain imaging is seen as an acceptable alternative. PMID- 1878287 TI - Global field power measurement versus classical method in the determination of the latency of evoked potential components. AB - The Global Field Power measurement (GFPM) was proposed as a method for the determination of component latency in multichannel evoked potential (EP) recordings (Lehmann and Skrandies 1980). In contrast to the classical method (CM) of peak latency determination using only two or three electrodes, multichannel recordings deal with data from twenty or more recording electrodes. We compared the GFPM and CM in evoked potential recordings. Sixty five subjects volunteered for 3 different response tasks. In a P3 oddball paradigm targets consisted of 2000 Hz tonebursts, nontargets of 1000 Hz tonebursts. Flash and Pattern Visual Evoked Potentials (VEP) also were recorded. At peak GFPM latency we found steeper voltage gradients than at CM latency. Both N200 and P300 had a significantly different topography at latencies determined by GFPM than at latencies determined by CM. For VEP we did not find a significant difference between CM and GFPM. Our Data suggests that multichannel recording adds additional dimensions to EP measurements and that only GFPM leads to an unbiased data-reduction as it determinesone momentary map in time which has maximal field strength. PMID- 1878288 TI - Desensitization of the EGF receptor alters its ability to undergo EGF-induced dimerization. AB - Treatment of A431 cells with EGF has been shown to induce the formation of EGF receptor dimers. Sucrose density gradient centrifugation as well as surface radio iodination followed by crosslinking were used to study further the properties of EGF receptor monomers and dimers as well as the regulation of dimer formation. We have shown previously that treatment of A431 cells with high doses of EGF at 37 degrees C leads to the desensitization of the EGF receptor without a significant loss of cell surface 125I-EGF binding [Kuppuswamy and Pike (1989) J. biol. Chem. 264, 3357-3363; Cunningham et al. (1989) J. biol. Chem. 264, 15351-15356]. Desensitization of the EGF receptor led to a decrease in the ability of receptor monomers to be induced to form dimers by EGF both in vivo and in vitro. These data suggest that the sensitivity of a cell to EGF may be modulated by altering the capacity of the EGF receptor to form oligomers. PMID- 1878289 TI - Epidermal growth factor and phorbol ester actions on the TSH induced down regulation of the isoenzyme I (PKA I) of cyclic AMP-dependent protein kinases in dog thyroid cell primary cultures. AB - In dog thyroid cell primary cultures the prolonged presence (up to 4-6 days) of TSH induced down regulation of the isoenzyme I (PKA I) of cAMP-dependent protein kinases. In the simultaneous presence of TSH and EGF this down regulation of PKA I was maintained, although it was slightly smaller than in assays without EGF. In contrast, the simultaneous presence of TPA, totally inhibited the TSH induced down regulation of PKA I. These results partly explain the previously observed additivity of TSH and EGF, and the non-additivity of TSH and TPA actions on cell proliferation in these cells. PMID- 1878290 TI - Clinical significance of retrograde flow in the vertebral artery. AB - Although retrograde vertebral artery flow was described over 100 years ago, its relationship to symptoms remains unclear. We documented 43 patients who were found by duplex scanning to have reverse flow in the vertebral artery. Of this group, seven patients (16%) were found to have symptoms described as typical for the "subclavian steal" syndrome. Nearly one-third were asymptomatic. Of the remaining patients, 13 (30%) presented with nonhemispheric symptoms while nine (21%) had hemispheric symptoms. Nine patients had "to and fro" flow in the vertebral artery. This variant was not found in subclavian steal patients but correlated with nonhemispheric symptoms. During follow-up (mean: 19 months) none of the asymptomatic patients became symptomatic, and there were no strokes or stroke-related deaths. Surgical procedures which restored antegrade vertebral artery flow did not necessarily improve symptoms of posterior circulation ischemia. In some patients improvement in posterior circulation symptoms was noted following carotid endarterectomy. It is concluded that retrograde flow in the vertebral artery is, per se, a benign entity. Accurate selection of surgical candidates remains imprecise. It will require not only identification of vertebrobasilar disease but as yet undefined tests to assure symptoms are due to these stenoses. PMID- 1878291 TI - Physician practices in the diagnosis and management of patients with pulmonary embolism. AB - To examine the diagnostic work-up and subsequent management of patients with pulmonary embolism, we retrospectively reviewed the medical records of 60 patients who had arteriographically proven pulmonary embolism. Ventilation perfusion scans were utilized in 47 patients and were classified as showing a high (55.3%), moderate (14.9%), low (8.5%), or indeterminate (21.3%) probability of pulmonary embolism. Of the 33 patients treated with anticoagulation, complications occurred in 10 (30.3%). Of the 39 patients treated with inferior vena cava filters, complications occurred in 16 (41.0%) patients, with the most clinically significant complication being recurrent pulmonary embolism, found to occur in one (2.6%) patient. For patients treated with anticoagulation, heparin was started an average of 0.3 (+/- 0.5) days following the initial suspicion of a pulmonary embolism. The average time to reach a therapeutic partial thromboplastin time level was 2.0 (+/- 1.8) days, and warfarin was started an average of 6.2 (+/- 4.1) days after heparin was begun. Among the 60 patients, five (8.3%) died from the pulmonary embolism, and two of these had at least a five day delay before diagnosis was made by pulmonary arteriography. Since the ventilation-perfusion scan had a sensitivity of 70.2% and a false negative rate of 8.5%, it is not always sufficiently accurate in making final treatment decisions, so there should be less hesitation in attaining pulmonary arteriograms. Therapeutic partial thromboplastin time levels should be more aggressively sought. Warfarin should be started within the first few days of heparin therapy. Inferior vena cava filters should be utilized in patients who have a contraindication to anticoagulation therapy or a complication from anticoagulation therapy. PMID- 1878292 TI - Local anesthesia for surgery on the foot: efficacy in the ischemic or diabetic extremity. AB - The efficacy, risks, and benefits of the use of local anesthesia for surgery on the foot were assessed in 75 patients who underwent 127 procedures with lower calf, ankle, metatarsal-ray, and digital blocks. There were 23 procedures on digits alone, 97 forefoot operations (transmetatarsal amputations, wound debridements, closures, osteotomies, joint resections), six ankle or hind-foot amputations, and one open ankle disarticulation. There were no complications directly related to the use of local anesthesia; specifically, no extension of preexisting infection or ischemia due to injection in the foot. There were three deaths (30-day mortality 4%). The procedures were uniformly well tolerated, even in patients with ongoing myocardial ischemia or severe metabolic disorders. Local anesthesia is a safe and effective method to perform local debridement or amputation of the foot in an ischemic or diabetic extremity. PMID- 1878293 TI - Late results of small untreated abdominal aortic aneurysms. AB - We report our experience with 73 patients who were initially selected for nonoperative management of an abdominal aortic aneurysm less than 5 cm in diameter. Size of the aneurysm was determined by ultrasound (34); arteriography (16); computerized tomography (17); plain x-ray (4); and magnetic resonance imaging (2). End points of the study were subsequent elective resection, rupture, death from cause other than rupture, or an intact aneurysm followed for a minimum of three years. Overall, 28 (38%) aneurysms were subsequently resected on an elective basis; four (5%) ruptured; 15 (21%) were intact at the time of the patient's death; and 26 (36%) remained intact during follow-up of 3 to 6.5 years. Indications for elective resection were aneurysm enlargement (21); symptoms suggesting impending rupture (3); and improvement in medical condition (4). In the 43 aneurysms initially less than 4 cm diameter, 16 (37%) had elective resection and one (2%) ruptured, and in the 30 that were 4-4.9 cm, 12 (40%) were resected and three (10%) ruptured. The four aneurysms that ruptured had enlarged to greater than 5 cm prior to rupture. We conclude that aneurysms less than 4 cm can be safely followed. Aneurysms 4-4.9 cm should be considered for operation, depending upon the size of the aneurysm, patient's life expectancy, and risk factors for surgery. Any aneurysm that enlarges should be resected, especially if the aneurysm becomes larger than 5 cm in diameter. PMID- 1878294 TI - Simultaneous resection of renal carcinoma and abdominal aortic aneurysm. AB - A 62-year-old man with a 6.5 cm abdominal aortic aneurysm and coexistent left renal cell carcinoma was treated by simultaneous radical left nephrectomy and abdominal aortic aneurysm repair. Care was taken to avoid potential infection of the bypass graft by inadvertent contamination with urine. Pathologic examination of the left kidney revealed a renal cell carcinoma, clear cell type, with no evidence of invasion into the renal vein or lymph node metastases. The patient had an uncomplicated recovery and is well and free of disease four years after operation. In cases of equivalently life threatening surgical diseases, simultaneous resection is warranted. PMID- 1878295 TI - Acute pancreatitis following aortic aneurysm repair: report of three cases. AB - This paper reports three cases of acute pancreatitis that occurred after repair of an abdominal aortic aneurysm. The aneurysms were ruptured in two patients and asymptomatic in one. No patient had biliary disease or history of pancreatitis or alcohol abuse. Two of the patients required operation for drainage and debridement; one died. The etiology and diagnosis are discussed. PMID- 1878296 TI - Acute arterial insufficiency of the male genitalia. AB - Three patients developed severe ischemia of the penis or scrotum from acute arterial occlusion. In one case, nonhealing ulceration of the glans developed after atheroembolism to the dorsal penile artery. One patient had penile ischemia after ligation of pelvic and femoral collateral circulation during repair of an aorto-bilateral-iliac artery aneurysm. A third patient had ischemia of the penis and scrotum from thromboembolism to the iliac arteries during repair of an aortoenteric fistula. Only seven patients have been described with acute arterial occlusion and severe ischemia of the male genitalia. A rare phenomenon because of rich collateral circulation, acute ischemia of the genitalia nevertheless must be recognized as a sign of severe vascular disease and a consequence of major arterial ligation or occlusion in the pelvis and groins. PMID- 1878297 TI - Late upper extremity embolic complications of occluded axillofemoral grafts. AB - The use of axillary femoral grafting in the treatment of patients at high risk for aortoiliac reconstruction has become a widely accepted treatment modality. Ischemia and even loss of the donor upper extremity have been reported to occur early after graft occlusion. This report describes three patients who developed emboli to the upper extremity at nine, 15, and 34 months following occlusion of their axillary femoral graft. Based on our experience, we consider an occluded axillofemoral graft a permanent threat to the viability of the donor upper extremity. Anatomic changes suggestive of potential ischemia include: presence of a blind pouch in the graft stump, or "Y" elongation of the artery with proliferative changes in the intima. PMID- 1878298 TI - Intraaortic balloon pump entrapment. AB - Catheter entrapment is a rare complication of intraaortic balloon counterpulsation caused by the formation of hard blood clot within the balloon itself. We present two cases of intraaortic balloon pump entrapment seen at the University Hospital, Boston. This phenomenon usually presents as a limb threatening vascular emergency. The entrapped catheter becomes stuck fast within the iliac system during withdrawal of the device, occluding arterial flow at that level. The etiology of this phenomenon, and a proposed management scheme is discussed. Preoperative radiographic determination of the level of entrapment may be necessary. We feel it is necessary to control the abdominal aorta prior to removal of an entrapped intraaortic balloon. PMID- 1878299 TI - Complications of anomalous origin of the right subclavian artery: case report and review of the literature. AB - A 35-year-old black woman presented with thrombosis of an anomalous right subclavian artery and distal arterial embolization. Initially, her right subclavian artery was reimplanted onto the common carotid artery, and a brachial artery embolectomy plus intraoperative thrombolytic therapy were used to reopen her distal arterial circulation. When her brachial artery repair thrombosed the following day, a distal ulnar artery bypass and repeat thrombolytic therapy were required to restore arterial patency. Six months later, she returned with severe, progressive, neointimal hyperplasia of her brachial artery and a second attempt at arterial reconstruction was unsuccessful. She eventually required a right below-elbow amputation. This patient demonstrated an anomalous right subclavian artery that presented with distal embolization without an antecedent history of severe atherosclerotic disease or the development of a right subclavian artery aneurysm. A review of the medical literature relating to complications of this anomaly is provided. PMID- 1878300 TI - An unusual cause of transient ischemic attacks: case report. AB - A 42-year-old black man, a physician, presented with a three week history of intermittent right arm and leg numbness and weakness, lasting about five minutes. This was not associated with headache, visual changes, seizures, aphasia or loss of consciousness. There was no history of head trauma, migraines, or previous attacks. Positive findings on physical examination were confined to a blood pressure of 182/80; evidence of hypertensive retinopathy; normal carotid pulses without bruits; and a Grade II/VI systolic ejection murmur with normal sinus rhythm. Initial hematocrit was 25.7%; white blood cell count 14,000 cu/mm with a normal differential; platelet count 532,000 cu/mm. An electrocardiogram showed left ventricular hypertrophy. Duplex scan demonstrated normal carotid bifurcations bilaterally, and arteriogram revealed no carotid or intracranial pathology. Hemoglobin electrophoresis revealed sickle cell disease of the SS type. He was treated with transfusion therapy and has remained asymptomatic at 40 months. Approximately 20% of children with the SS type sickle cell disease will have cerebrovascular symptoms caused by small intracranial artery occlusion due to sludging of the abnormal hemoglobin. This unusual cause of transient ischemic attacks can occur in older patients of African-American ancestry and must be recognized to enable early and effective therapy with exchange transfusion. PMID- 1878301 TI - Celiac artery aneurysm. AB - Aneurysms of the celiac artery are unusual lesions and account for only 4% of all splanchnic aneurysms. In recent years, the incidence has been noted to rise because of the increased use of sonography, computerized tomography, and arteriography. Although patients are often asymptomatic at the time of diagnosis, the risk of rupture is high; therefore, surgical resection should be undertaken in acceptable candidates. We report the case of a large celiac artery aneurysm treated with distal pancreatectomy and celiac artery aneurysmectomy. PMID- 1878302 TI - Hyperparathyroidism presenting as an unusual cause of lower extremity gangrene. AB - Vascular surgeons are often consulted on the management of lower extremity ulcerations and gangrene which are commonly due to atherosclerotic arterial occlusive disease or to chronic venous insufficiency. The following report describes an unusual case of severe lower extremity cutaneous gangrene associated with secondary hyperparathyroidism and a review of the literature. PMID- 1878303 TI - Ischemia/reperfusion injury in skeletal muscle. AB - Ischemia/reperfusion injury to skeletal muscle may be explained by a cascade of cellular and systemic events initiated by an ischemic period followed by reperfusion. During the period of ischemia there is a gradual reduction of intracellular energy stores. Adenosine triphosphate is gradually depleted despite the buffering effect of creatine phosphate which is present in large stores in muscles. As well, glycogen stores are depleted with resultant production of small amounts of energy and large accumulations of lactate. Upon reperfusion there is a reactive hyperemia, resulting in an overall increase in muscle blood flow, despite the fact that areas may continue to be underperfused. Results of this blood flow are mixed with the beneficial effects of removing metabolic by products and supplying exogenous substrates and oxygen. However, this blood flow also causes harmful effects by washing out necessary precursors for adenine nucleotide resynthesis. Production of oxygen free radicals occurs with resultant membrane lipid peroxidation, and calcium influx occurs upon reoxygenation with resultant disruption of oxidative rephosphorylation in the mitochondria. The sequestration of white blood cells in the muscle due to up regulation of both neutrophil receptors and endothelial leukocyte adhesion molecules results in a prolongation of the reperfusion injury. This subsequently results in damage to remote organs, including lung, heart, and kidneys. The future for therapeutic interventions aimed at reducing this injury lie mostly in the ability to modulate the reperfusion effect. PMID- 1878304 TI - Intestinal ischemia. PMID- 1878305 TI - Assessing school-related stressors and coping mechanisms in adolescents. AB - Despite a plethora of instruments used to measure stressors and coping mechanisms in adolescents little attention has been paid to issues of reliability and validity. In an endeavour to overcome this problem, a statistical methodology was implemented to develop scales from existing item sets. Items from Kohn and Frazer's (1986) Academic Stress Scale were combined with Strutynski's (1985) list of problems and, together with items from Patterson and McCubbin's (1987) Adolescent Coping Orientation for Problem Experiences, were administered to 1699 secondary school students in Australia. Two scale, the School Stressors Inventory for Adolescents (SSIA) and the Coping Inventory for Adolescents (CIA), were produced with five and four subscales respectively. Both have strong face and factorial construct validity, and high to modest reliability. PMID- 1878306 TI - A prospective study in the Australian petroleum industry. I. Mortality. AB - This paper reports the mortality experience of employees of the Australian petroleum industry from 1981 to 1989. Two surveys by personal interview incorporated more than 15,000 employees representing 92% of the eligible population. Subjects were included in the analysis after completing five years of service in the industry. At the time of this report the cohort does not include sufficiently large numbers of women for useful analysis; results presented are restricted to men. By 31 December 1989, 76,529 person-years of observation had accumulated for male mortality with 241 deaths. The standardised mortality ratio (SMR) analysis showed a favourable mortality experience for most causes with overall cancer rates slightly lower than those of the national population. Whereas deficits were seen in some cancer sites, notably lung cancers (SMR 0.5, 95% confidence interval (95% CI) 0.3-0.8), mortality for lymphohaematopoietic cancers, notably leukaemia (SMR 1.6, 95% CI 0.6-3.4) suggested increased risk. The SMR for cancers of the pleura was 3.9 (95% CI 0.8-11). Two of the three cases seen had previous employment, however, in industries with likely exposure to asbestos. PMID- 1878307 TI - A prospective study in the Australian petroleum industry. II. Incidence of cancer. AB - This paper reports incidence of cancer in employees of the Australian petroleum industry from 1981 to 1989. Two surveys by personal interview incorporated more than 15,000 employees, representing 92% of the eligible population. Subjects were included in the analysis after completing five years of service in the industry. At the time of this report the cohort did not include sufficiently large numbers of women for useful analysis; results presented are restricted to the men. On 31 December 1989, 50,254 person-years of observation had accumulated in the men with 152 incident cancers reported. The standardised incidence ratio (SIR) analysis showed overall cancer rates close to those of the national population. Whereas deficits were seen in some cancer sites, notably lung cancer (SIR 0.5, 95% confidence internal (95% CI) 0.3-0.9), incidence rates for some other cancer sites suggested increased risk. An excess of observed over expected cases was present in all subcategories of lymphohaematopoietic cancer except Hodgkin's disease (no cases), and was most apparent in myeloid leukaemia (SIR 4.0, 95% CI 1.6-8.2). The other major site with a raised number of cases observed over expected was melanoma (SIR 1.4, 95% CI 0.8-2.1). PMID- 1878308 TI - Retrospective cohort mortality study of workers at an aircraft maintenance facility. I. Epidemiological results. AB - A retrospective cohort study of 14,457 workers at an aircraft maintenance facility was undertaken to evaluate mortality associated with exposures in their workplace. The purpose was to determine whether working with solvents, particularly trichloroethylene, posed any excess risk of mortality. The study group consisted of all civilian employees who worked for at least one year at Hill Air Force Base, Utah, between 1 January 1952 and 31 December 1956. Work histories were obtained from records at the National Personnel Records Centre, St. Louis, Missouri, and the cohort was followed up for ascertainment of vital state until 31 December 1982. Observed deaths among white people were compared with the expected number of deaths, based on the Utah white population, and adjusted for age, sex, and calendar period. Significant deficits occurred for mortality from all causes (SMR 92, 95% confidence interval (95% CI) 90-95), all malignant neoplasms (SMR 90, 95% CI 83-97), ischaemic heart disease (SMR 93, 95% CI 88-98), non-malignant respiratory disease (SMR 87, 95% CI 76-98), and accidents (SMR 61, 95% CI 52-70). Mortality was raised for multiple myeloma (MM) in white women (SMR 236, 95% CI 87-514), non-Hodgkin's lymphoma (NHL) in white women (SMR 212, 95% CI 102-390), and cancer of the biliary passages and liver in white men dying after 1980 (SMR 358, 95% CI 116-836). Detailed analysis of the 6929 employees occupationally exposed to trichloroethylene, the most widely used solvent at the base during the 1950s and 1960s, did not show any significant or persuasive association between several measures of exposure to trichloroethylene and any excess of cancer. Women employed in departments in which fabric cleaning and parachute repair operations were performed had more deaths than expected from MM and NHL. The inconsistent mortality patterns by sex, multiple and overlapping exposures, and small numbers made it difficult to ascribe these excesses to any particular substance. Hypothesis generating results are presented by a variety of exposures for causes of death not showing excesses in the overall cohort. PMID- 1878309 TI - Retrospective cohort mortality study of workers at an aircraft maintenance facility. II. Exposures and their assessment. AB - Methods are presented that were used for assessing exposures in a cohort mortality study of 15,000 employees who held 150,000 jobs at an Air Force base from 1939 to 1982. Standardisation of the word order and spelling of the job titles identified 43,000 unique job title organisation combinations. Walkthrough surveys were conducted, long term employees were interviewed, and available industrial hygiene data were collected to evaluate historic exposures. Because of difficulties linking air monitoring data and use of specific chemicals to the departments identified in the work histories, position descriptions were used to identify the tasks in each job. From knowledge of the tasks and the chemicals used in those tasks the presence or absence of 23 chemicals or groups of chemicals were designated for each job organisation combination. Also, estimates of levels of exposure were made for trichloroethylene and for mixed solvents, a category comprising several solvents including trichloroethylene, Stoddard solvent, carbon tetrachloride, JP4 gasoline, freon, alcohols, 1,1,1 trichloroethane, acetone, toluene, methyl ethyl ketone, methylene chloride, o dichlorobenzene, perchloroethylene, chloroform, styrene, and xylene. PMID- 1878310 TI - Asphalt and risk of cancer in man. AB - Epidemiological publications regarding the carcinogenic potential of asphalt (bitumen) are reviewed. In 1984 the International Agency for Research on Cancer (IARC) stated that there is "inadequate evidence that bitumens alone are carcinogenic to humans." They did, however, conclude that animal data provided sufficient evidence for the carcinogenicity of certain extracts of steam refined and air refined bitumens. In the absence of data on man, IARC considered it reasonable to regard chemicals with sufficient evidence of carcinogenicity in animals as if they presented a carcinogenic risk to man. Epidemiological data for man accumulated since the IARC report do not fulfil the criteria for showing a causal association between exposure to asphalt and development of cancer. The studies cited all suffer from a lack of data on exposure or potential confounders, which are necessary to establish whether or not such an association may or may not exist. In view of the evidence (or lack thereof) regarding asphalt today, an appropriate public health attitude suggests at least that action be taken to protect those working with asphalt by monitoring the workplace, taking whatever steps are possible to minimise exposures and to inform workers of potential hazards. At the same time, a need exists for well designed analytical epidemiological studies to determine whether a risk of cancer in man exists from exposure to asphalt. PMID- 1878311 TI - Risk assessment using exposure intensity: an application to vermiculite mining. AB - Estimation of exposure-response relations from epidemiological data is complicated by the fact that exposures usually vary in intensity over time. Cumulative exposure indices, which do not separate the effects of intensity and duration, are commonly used to circumvent this problem. In this paper the estimation of relative risk for specific ranges of exposure intensity from such data is considered using existing statistical methods for fitting multivariate relative risk models. This has the advantage that it does not assume that exposure intensity and duration have equivalent effects on risk. It also throws light on the possible existence of a threshold. The procedure was applied to data from a cohort of 406 vermiculite miners to examine the lung cancer risk associated with exposure to fibrous tremolite, which contaminated the vermiculite. The pattern of exposure-response differed substantially from that obtained using a cumulative exposure index to assess risk. PMID- 1878312 TI - Effects of consumption of ethanol on the biological monitoring of exposure to organic solvent vapours: a simulation study with trichloroethylene. AB - This study illustrates possible influences of consumption of ethanol on the pharmacokinetic behaviour of inhaled trichloroethylene (TRI) in relation to biological monitoring of exposure. The results were obtained for a standard male worker of 70 kg by physiologically based pharmacokinetic modelling. Depending on the pattern of consumption of ethanol, enzyme inhibition or induction was assumed to prevail in this worker. The inhibition and induction were modelled by assuming competitive metabolic interaction between TRI and ethanol and increased maximum velocity (Vmax) of TRI metabolism respectively. Ingestion of moderate amounts of ethanol before the start of work or at lunch time, but not at the end of work, caused pronounced increases in blood TRI concentrations and decreases in the urinary excretion rates of TRI metabolites, this effect lasting until the next day. The effects were smaller the higher the exposure concentration of TRI. Induction of TRI metabolism, supposedly by consumption of ethanol the previous evening, caused only small changes in the pharmacokinetic profile at 50 ppm, but appreciable changes at 500 ppm. PMID- 1878313 TI - New perspectives in biomonitoring liver function by means of serum bile acids: experimental and hypothetical biochemical basis. AB - The functional activity of the liver and the variety of its responses to injury makes the choice of appropriate tests of function a difficult task. Because of the highly efficient uptake of bile acids by the normal hepatocyte, the determination of serum bile acid (SBA) concentration has been proposed as a test to detect early changes of liver function not associated with cytotoxicity. Several biomonitoring studies have been carried out on subjects occupationally exposed to hepatotoxic substances, by evaluating SBAs as indicators of early liver dysfunction. Even though these studies are not exactly comparable because of the different protocols adopted, most of them show a significant increase in SBA concentrations among the exposed subjects compared with unexposed controls. Furthermore, higher prevalences of subjects with abnormal SBA concentrations occur in those exposed to mixtures of organic solvents. Increased SBA concentrations among the subjects exposed to various xenobiotics have been explained by assuming a change in function of hepatocytes. As regards the nature of the mechanisms involved in the increase in SBA concentrations, recent experimental observations pointed out that some chlorinated aliphatics were able to inhibit cell membrane ATPases and alter cytosolic calcium homeostasis. The lack of any relation, however, between exposure and SBA concentrations remains an important point to clarify and at present prevents the use of measurement of SBA concentrations as an index of effect. PMID- 1878314 TI - Inter and intraindividual variations in plasma cholinesterase activity and substance concentration in employees of an organophosphorus insecticide factory. AB - During a period of 10 months, inter and intraindividual variations in plasma cholinesterase (ChE) activity were studied in 331 employees of an organophosphorus insecticide factory, and in 193 healthy volunteers without occupational exposure to known ChE inhibitors. Repeated (n = 6) measurements of ChE activity and ChE substance concentration were performed in 410 subjects. The study showed substantial intraindividual variations of ChE activity and ChE substance concentration (up to 40%) in the employees and in the reference group. When effects due to sex, ChE-1 phenotype, body weight, and height were considered, one subgroup of employees of the organophosphorus insecticide factory showed a significantly lower average ChE activity than other subgroups; as ChE substance concentrations were found to be proportionally decreased, it was concluded that the low ChE activity was unrelated to occupational exposure. A combined determination of ChE activity and ChE substance concentration is recommended as a rational diagnostic tool when an unexpected decrease of plasma ChE activity is registered in people joining organophosphorus insecticide health surveillance programmes. PMID- 1878315 TI - Determination of urinary 2,5-hexanedione concentration by an improved analytical method as an index of exposure to n-hexane. AB - 2,5-Hexanedione is a main metabolite of n-hexane and is considered as the cause of n-hexane polyneuropathy. Therefore, it is useful to measure 2,5-hexanedione for biological monitoring of exposure to n-hexane. The analytical methods existing for n-hexane metabolites, however, were controversial and not established enough. Hence, a simple and precise method for determination of urinary 2,5-hexanedione has been developed. Five ml of urine was acidified to pH 0.5 with concentrated hydrochloric acid and heated for 30 minutes at 90-100 degrees C. After cooling in water, sodium chloride and dichloromethane containing internal standard were added. The sample was shaken and centrifuged. 2,5 Hexanedione concentration in an aliquot of dichloromethane extract was quantified by gas chromatography using a widebore column (DB-1701). Urinary concentration of 2,5-hexanedione showed a good correlation with exposure to n-hexane (n = 50, r = 0.973, p less than 0.001). This method is simple and precise for analysis of urinary 2,5-hexanedione as an index of exposure to n-hexane. PMID- 1878316 TI - A cohort mortality study and a case-control study of workers potentially exposed to styrene in the reinforced plastics and composites industry. PMID- 1878317 TI - Blinks as an index of cognitive activity during reading. AB - Horizontal and vertical EOG recordings of eye movements were analyzed to determine the spatial and temporal distribution of blinks and the patterns of eye movements (saccades and fixation pauses) exhibited by six subjects during the reading of stories presented in two formats (on paper and on a VDT). The frequency and placement of blinks was not affected by the presentation condition. Blinks were determined to be non-randomly distributed during reading. Significantly more blinks (36%) occurred in conjunction with saccades than the proportion of time consumed by saccades (12%) would predict. Significantly more blinks (36%) occurred in the vicinity of line change saccades, which accounts for 15% of reading time, and with fixation pauses associated with regressions (42%), which accounts for 26% of reading time, than with fixation pauses during normal reading (22%), which accounts for 60% of reading time. The results of the study suggest that blink behavior during reading is under perceptual and cognitive control. PMID- 1878319 TI - Blocking observed in human eyelid conditioning. AB - The status of blocking in human eyelid conditioning was examined in a series of four experiments modelled on rabbit nictitating membrane (NMR) procedures to ensure comparability with the animal literature. The first three employed Tones and Lights as CSs and a preliminary experiment established equivalent salience of these stimuli. The fourth employed all light conditioned stimuli (CSs). Each of the experiments balanced order of presentation of blocked and non-blocked stimuli in extinction; each yielded reliable evidence of blocking tested in extinction. However, the blocking effects were attenuated or abolished in those groups receiving the to-be-blocked stimulus on the first trial in extinction. The results show blocking to be a relatively weak, easily disrupted phenomenon compared with rabbit studies. They suggest that rapid re-appraisal of stimulus significance plays a more important role in human subjects than has been observed in animal studies. PMID- 1878318 TI - The fear potentiated startle effect. Blink reflex modulation as a result of classical aversive conditioning. AB - A differential conditioning study examined whether an acoustic startle probe, presented during extinction of an aversively conditioned visual stimulus, potentiated the reflex eyeblink response in humans and whether this potentiation varied with the change in affective valence of the conditioned stimulus. Sixty college students were randomly assigned to view a series of two slides, depicting either unpleasant/highly arousing, unpleasant/moderate arousing, neutral/calm, pleasant/moderate arousing or pleasant/highly arousing scenes and objects (duration: 8 sec). During preconditioning (8 trials) and extinction (24 trials) acoustic startle probes (white noise bursts [50 ms; 95 dBA] were administered during and between slide presentation). During acquisition (16 trials) CS+ was reinforced by an electric shock. Startle response magnitudes significantly increased from preconditioning to extinction and were substantially larger to CS+. Conditioned startle reflex augmentation linearly increased with the pleasantness of the slides. Furthermore, subjects showed a greater post conditioning increase of judged aversiveness to slides that they had previously reported to be more pleasant, exactly paralleling the startle reflex results. PMID- 1878320 TI - Blocking and unconditioned response diminution in human classical autonomic conditioning. AB - This paper summarizes the results of three experiments on blocking and unconditioned response diminution in human SCR conditioning. Recent theories of conditioning propose that reduced processing of the unconditioned stimulus due to conditioning results in reduced unconditioned response magnitude and in blocking of conditioning of a second conditioned stimulus when it is in compound with the previously conditioned stimulus. In these experiments, clear evidence of diminution of the unconditioned response was obtained in all three studies, but blocking was found only in the third study, which employed a within-subject design and in which the blocking was observed only after at least one extinction trial on both the blocked and nonblocked stimuli. Order of testing was not a factor in this delayed blocking effect. These results do not support the view that blocking occurs because of reduced processing of the unconditioned stimulus in the unconditioned response diminution sense. PMID- 1878321 TI - Component summation or configuration in human eyelid conditioning depends upon stimulus properties. AB - The experiment reviewed here merges Garner's (1974) distinction of separable and integral stimulus properties with the field of Pavlovian eyelid conditioning with human subjects. According to one rule, two sets of stimuli (separable vs integral) were constructed. A differential compound conditioning procedure was used with one group of subjects being trained with a subset of the separable material and then tested with a new subset. The same procedure was used with a second group but with integral material. The experiment showed a reversal of conditioning effects, depending on the properties of stimuli. Separable compounds showed results as predicted by elementistic conditioning theories: the associative values of the elements summed up. With integral compounds, the associative values of the elements were irrelevant. Instead, integral compounds were processed and classified primarily on the basis of similarity. PMID- 1878322 TI - The quality of evidence. PMID- 1878324 TI - Sucking habits: clinical management in dentistry. AB - Excellent results were obtained by using the classical palatal crib for the patient, who is appraised as having morphological, functional and psychological changes resulting from finger and/or pacifier sucking habits. PMID- 1878325 TI - Interceptive correction of anterior crossbite. AB - The purpose of this paper was to evaluate a passive method to correct anterior crossbite of only one incisor by creating a composite inclined plane. A total of 15 children were selected, aged 6 to 8. The results at the end of one week showed that in all cases the incisor was in normal position. PMID- 1878323 TI - Blood pressure hyperreactivity in non-human primates during dietary sodium combined with behavioral stress. AB - The potential for behavioral stress alone or combined with dietary salt to augment pressor reactivity to the onset of daily experimental sessions was examined in normotensive, intact baboons over the course of four months. During twice daily experimental sessions, adult male baboons experienced food/shock conflict such that lever pulling not only served to earn food, but was also occasionally punished with cued mild electric shock. Blood pressure and heart rate were measured during a baseline period of fixed-ratio food reinforcement (3 weeks), during conflict stress (2 weeks), and after dietary salt was added to the daily conflict protocol (CONFLICT + SODIUM, 3 weeks). Reactivity, i.e., acute changes in blood pressure and heart rate to the daily experimental sessions, was not evident during food reinforcement sessions nor during the CONFLICT stress alone condition. The addition of a high salt diet virtually doubled blood pressure increases and heart rate decreases to the onset of experimental sessions. Average reactivities during CONFLICT + SODIUM periods were 11.2/7.9% delta for SBP/DBP (systolic/diastolic blood pressure, mmHg), and -5.65% delta for HR (heart rate, BPM). Neither atenolol nor hydrochlorothiazide diuretic significantly altered cardiovascular reactivity during CONFLICT + SODIUM in comparison to a preceding non-drug CONFLICT + SODIUM period. When atenolol and diuretic effects were directly compared, atenolol mildly augmented, while diuretic mildly decreased DBP but not SBP reactivity during CONFLICT + SODIUM. Reactivity was eliminated after salt loading and behavioral sessions were terminated. These findings provide evidence that enhanced salt ingestion may synergistically act with behavioral stress to produce pressor hyperresponsiveness to otherwise benign environmental events. PMID- 1878326 TI - Primary impaction of primary teeth: a review and report of three cases. AB - Primary impaction of primary teeth is rare. Only ten cases have been found in the world literature. It affects almost always second molars and the finding is usually occasional. Three cases of this abnormality, two of the upper jaw and one of the mandible, are presented. The analysis of the characteristics of these cases and the cases in the literature, suggests that ankylosis has probably a leading role in the etiopathogenesis. The following criteria for a correct diagnosis is presented: 1) deep retention into the bone; 2) absence of caries, restorations and resorptions; 3) frequent passing of the corresponding permanent premolar; and possible retention of the corresponding adjacent tooth. More attention is recommended in the study of the lesion for the future. PMID- 1878327 TI - Comparison of craniofacial morphology in monozygotic twins with their siblings. AB - Lateral cephalometric radiographs from 33 families of monozygotic twins and their siblings were digitized. Eight skeletal parameters were measured: FA to SN, SNA, SNB, ANB, angle of convexity, mandibular plane to SN angle, Y axis and pogonion to NB distance. Monozygotic twin pairs and their siblings showed a normal distribution pattern for all the skeletal parameters, except the pogonion to NB distance measurement. There was found to be a statistically significant correlation between age and facial angle and ANB. A familial aggregation effect was found for SNA, ANB and angle of convexity. Some genetic influence was found for FA, mandibular plane angle and Y axis, while the Pg to NB distance showed neither genetic influence, nor a familial aggregation. PMID- 1878328 TI - Background factors of enamel focal demineralization in groups of Finnish and Russian children. AB - The aim of this study was to analyze the occurrence of EFD lesions in relation to some background factors in Finnish and Soviet children. Children aged 7, 9 and 12 years (n = 1187) were examined clinically in Helsinki, Kuopio (Finland), Moscow and Leningrad (USSR). A questionnaire sent to the parents was used to collect data on toothbrushing frequency, use of sweets, cakes, soft drinks, sugar sweetened tea/coffee and mother's education. In addition to bivariate analysis, log-linear regression models were used for comparing the simultaneous association in two ethnic groups. In general, the Finnish children had more EFD lesions than the Soviet children did. Among the Finns no consistent associations were found between the number of EFD lesions and the use of different sugar products or differences in toothbrushing habits. The number of EFD lesions decreased consistently according to mother's education with the Finnish children, but not with the Soviet children. The final multivariate model for Finnish children included age, toothbrushing frequency, place of residence (Kuopio) and use of soft drinks. The respective model for the Soviet children included age and place of residence (Leningrad). Evidently, the demineralization process or tooth resistance differs in these two ethnic groups. PMID- 1878330 TI - The effect of acid etching times on ground primary enamel. AB - The purpose of this study was to investigate the relationship of etching times on the effect of acid etching on the ground primary enamel with respect to the quality of etching patterns. Labial surfaces of 40 extracted or exfoliated caries free primary anterior teeth were used. The outer, middle and inner enamel layers were ground without water cooling with a carbide bur from the distal to the mesial direction on the same labial surfaces of the enamel. Each layer was divided into incisal, central and cervical areas. Forth percent phospholic acid gel was used for each etching time group, 10, 20, 30 and 60 seconds. All specimens were washed with an air spray for 30 seconds. The following observations were obtained using the SEM: 1. Over-etching was evident in all cases etched for 60 seconds and this characteristic was particularly prominent in the inner enamel layers. 2. Thirty seconds was the optimal time for etching on the ground primary enamel. PMID- 1878329 TI - Effect of the mineralizing agent on the permanent teeth. AB - In a two-year pragmatic clinical trial, the effect of the mineralizing agent was evaluated on permanent teeth of the first eruption group among Finnish children (7-years old at the beginning of the study) with a low prevalence of DFS. In the test group (n = 123, biweekly mouthrinsing with a 2% solution of mineralizing agent and 0.2% NaF solution) the percentage reduction in increment of both EFDS and DFS was high, whereas in the control group (n = 123, biweekly mouthrinsing with placebo and 0.2% NaF solutions) the incidence for symptoms of caries disease did not differ from that normally found in this age cohort. Positive clinical effect of tested solution was age-related and was associated with remineralization of old and inhibition of occurrence of new EFD lesions. PMID- 1878331 TI - Designing dental health education materials for schoolteachers: formative evaluation research. AB - In the past, many school based dental health education programs have appeared to fail to bring about changes in children's behavior or measureable improvements in oral health. The reasons why this has been so are not always clear, but part of the explanation may be that inadequate attention has been paid to the research preceding the development of the dental health education materials used in the programs. This paper describes a rational planning cycle for evaluation research, which includes problem definition research, planning research, audience pre testing and post-production audience testing for acceptability. Further stages involve post-dissemination evaluation, which include measures of effectiveness and implementation, but this paper argues that the four phases described above constitute a logical means of providing target groups with appropriate, acceptable and efficacious material. PMID- 1878332 TI - An unusual case of hypodontia with extensive caries: a multidisciplinary treatment approach. PMID- 1878333 TI - Parotitis in a three-year-old. AB - Facial swelling cannot routinely be attributed to dento-alveolar infections until a thorough head, neck and oral examination has been completed. Facial swelling from parotitis is not commonly encountered in the pediatric patient. The purpose of this report was to document a case of unilateral parotid gland infection presumably secondary to traumatic obstruction of Stenson's duct. The parotitis resolved following a course of oral penicillin VK and lemon juice to stimulate salivary flow. Several parotid gland disorders which involve facial swelling were discussed. PMID- 1878334 TI - Calcium channel blocker prevents stress-induced activation of renin and aldosterone in conscious pig. AB - A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, we studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress. Renin and aldosterone levels were repeatedly measured by radio-immunoassay in blood samples taken periodically over 24 hours from a chronically implanted arterial cannula. Pretreatment of the animals (N = 11) with nisoldipine, 2 x 20 mg p.o. daily for 2 days before and on the day of immobilization, transiently attenuated the stress induced increase of plasma renin activity and completely prevented the rise of aldosterone, as compared to nontreated controls (N = 10). The finding that nisoldipine suppresses RAA activation induced by a nonpharmacologic stimulus in the conscious intact animal may have clinical implications. PMID- 1878335 TI - Double-blind, randomized comparative study of the antihypertensive effect of nicardipine slow-release and nifedipine slow-release in hypertensive patients with coronary heart disease. AB - The main aim of this study was to investigate whether a new slow-release formation of nicardipine can control hypertension and whether its antihypertensive effect is manifest throughout the dose intervals. In a randomized, double-blind placebo-controlled study, the antihypertensive effect of two calcium antagonists (Type II) was investigated in two independent groups of hypertensive patients with coronary artery disease. One group of patients received 40 mg nicardipine slow-release b.i.d. and the other 20 mg nifedipine slow-release b.i.d. The effect of the active drugs on blood pressure (BP), heart rate, and hemodynamics was compared with placebo within each group. In addition, a group comparison was made to establish whether nicardipine had any advantage over nifedipine. Twenty-eight patients [27 female, 1 male; 55 (41-72) years old], 18 with previous myocardial infarction (MI) entered the study (nicardipine, 15 patients; nifedipine, 13 patients). A placebo period of 3 days was followed by a 13-day drug treatment period. From the first to last trial day, BP and heart rate were measured three times daily. At the end of the placebo and the active drug periods, the following measurements were carried out: ambulatory BP monitoring by half-hourly recording for 12.5 hours with the Remler system, ergometric tests with ECG, and right heart catheterization. Both drugs lowered the BP at rest, during exercise, and during usual daily activities. The antihypertensive effect of nicardipine was significant for the daytime mean arterial BP (MAP) and for systolic BP and diastolic BP at various stages of the exercise tests. The difference between the effect of nicardipine and nifedipine was not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878336 TI - Subcellular localization of prostaglandin-E2 in rat heart tissue. AB - It has been reported that isolated rat heart myocytes and cardiac mesenchymal cells convert arachidonic acid mainly into three types of prostaglandins (PGs): PGE2, PGF2 alpha, and PGI2. In addition, we have demonstrated that fresh atrial slices of patients with heart-valve disease contain appreciable quantities of PGE2 and PGF2 alpha. However, there have been no reports on the subcellular localization of the prostaglandin system in heart muscle tissue. The present study was performed to define the distribution of PGE2 in mitochondrial, microsomal, and cytosolic fractions, isolated by differential centrifugation from homogenates of fresh normal rat atrium and ventricle slices. In addition, we determined whether differences exist in PGE2 levels between atrial subcellular fractions and those of ventricular fractions. The results showed that PGE2 was located mainly in the high-speed cytosolic supernatant fraction of the heart homogenates analyzed. Furthermore, PGE2 concentrations (ng/mg protein) were significantly higher in fractions obtained from atrial than those of ventricular tissue. PMID- 1878337 TI - Murine polymorphonuclear leukocytes synthesize and secrete the third component and factor B of complement. AB - Complement proteins in serum are synthesized mostly by hepatocytes and many other cell-types have also been shown to synthesize complement in various tissues. However, polymorphonuclear leukocytes (PMNs) have never been reported to secrete complement. This paper demonstrates the synthesis and secretion of C3 and factor B by murine peritoneal exudate PMNs elicited with OK432 (Streptococcus preparation). Using [35S]methionine incorporation and immunoprecipitation, C3 and factor B produced by PMN are found to be antigenically and physically identical to macrophage C3 and factor B. ELISA analysis reveals that culture supernatant of PMN--free of macrophage contamination--contains C3 antigen, and both flow cytometric analysis and immunoperoxidase staining also demonstrate the presence of intracellular C3 using special precautions to eliminate non-specific staining. The role of complement produced by PMN is currently unknown, but it is very important to take this new finding into consideration for further clarification of the roles of complement in extravascular inflammatory sites. PMID- 1878338 TI - Identification and characterization of a prolactin-like polypeptide synthesized by mitogen-stimulated murine lymphocytes. AB - Previously, we have reported that concanavalin A (Con A)-stimulated murine splenocytes synthesize and secrete into the medium a substance with prolactin (PRL)-like properties. Western blot analysis of the culture medium of Con A stimulated murine splenocytes identified a PRL-like polypeptide (Ly-PLP) with an apparent molecular weight (Mr) of 46 kd. Rabbit anti-rat PRL antibody (S-9, NIDDK) was used for immunostaining. Specificity was proved by the absence of a band in properly preabsorbed primary and secondary antibodies. Electroeluted Ly PLP enhanced the mitogenic response of lymphocytes to Con A. In situ hybridization analysis of dispersed lymphocyte smears demonstrated the presence of an mRNA that hybridized with a rat PRL cDNA probe. The size of the mRNA species was 1.4 kb on Northern blot analysis. Two-dimensional peptide map analysis of pituitary PRL and Ly-PLP showed three peptides with identical migration characteristics. Western blot analysis of lymphocyte culture medium following Con-A-affinity column treatment provided evidence that the Ly-PLP was a non-glycoprotein. Therefore, we conclude that Ly-PLP represents a structural variant of pituitary-PRL (Pit-PRL), and provide evidence to strongly suggest that it is a novel lymphokine. PMID- 1878339 TI - TNF inhibits malaria hepatic stages in vitro via synthesis of IL-6. AB - We examined the capacity of murine recombinant tumor necrosis factor (rmTNF) to induce an inhibitory effect at the hepatic stage on malaria induced by Plasmodium yoelii sporozoites. When injected three times, 1.0 micrograms of rmTNF was found to protect 78% of mice against a sporozoite challenge. In contrast, whatever the dose and the schedule of administration, no inhibition was observed when purified hepatocyte cultures were infected with P. yoelii. The addition of non-parenchymal hepatic cells to hepatocyte cultures restored the capacity of TNF to modulate hepatic stage development, leading to up to 44% inhibition. Antibodies to interleukin 6 reversed the anti-parasite activity in the co-culture system. PMID- 1878340 TI - Alternative complement pathway activation by HIV infected cells: C3 fixation does not lead to complement lysis but enhances NK sensitivity. AB - HIV infected T and monocytic cell lines could activate and fix C3 fragments when incubated in human serum under conditions allowing for activation of the alternative complement pathway. Normal T lymphocytes incubated with HIV could also activate and fix C3. This activity was, at least in part, the property of the virus itself since cell-free HIV could efficiently activate C3. The C3 activating HIV infected cells were resistant to complement-mediated lysis, even after prolonged incubation periods. However, their sensitivity to cell-mediated natural killing increased, presumably due to their interaction with complement receptor bearing NK lymphocytes. The results suggest that the alternative complement pathway may contribute to the depletion of CD4+ T lymphocytes during HIV infection in vivo. PMID- 1878341 TI - Human complement component factor B rescues HIV-1-infected leukemic T cells from cytopathic death. AB - The addition of 5-10% of fresh normal human serum (NHS) from normal individuals into a culture of primarily HIV-1-infected CD4+ leukemic T-cell lines CEM and MT4 was found to rescue the infected cells from cytopathic death, enabling the cells to achieve growth within 10 days. The HIV-1-infected cells cultured in ordinary medium with fetal calf serum (FCS) all died within 10 days. The effect of NHS was ascribed to human complement component factor B and one or more factor B dependent heat-labile co-factors. The cells which survived in the presence of NHS rapidly lost surface expression of CD4 and became completely resistant to rechallenge by HIV-1. Viral genomes were dramatically reduced in surviving cells within 30 days, and one cell-line CEM completely expelled them during this period. The results suggest that factor B has protective and potential therapeutic significance in HIV-1 infection. PMID- 1878342 TI - Expression of medial class I histocompatibility antigens on RMA-S mutant cells. AB - The RMA-S mutant T cell line is defective in H-2b restricted antigen presentation and has markedly reduced surface expression of Kb and Db. We examined RMA-S for the expression of the medial class I histocompatibility antigens Qa1b and Mta. While RMA-S targets varied in their susceptibility to lysis by cytotoxic T lymphocytes (CTL) specific for Qa1b, Mta levels were detectable but consistently low compared to the parent RMA cell line. Addition of synthetic ND1 alpha 1-26 or ND1 alpha 1-17 peptides that mimic MTF alpha (the ligand of Mta) increased killing of RMA-S by anti-Mta alpha CTL to levels comparable to or better than RMA, with 300 nM peptide being fully effective. None of the MTF peptides increased the killing of RMA-S by anti-H-2b or anti-Qa1b CTL, even at the highest (1 microM) peptide concentrations. RMA-S cells treated with 100 microM of either the ND1 alpha 4-26 or ND1 alpha 1-26 peptides showed a small increase in the fluorescent staining for beta 2-microglobulin but not for H-2Kb or H-2Db. These results show that Mta and Qa1b, although affected, are not obliterated by the defect in RMA-S cells; that the association of MTF peptides with HMT is exclusive; and that MTF enters the endoplasmic reticulum in the same fashion as other endogenous peptides. PMID- 1878343 TI - HLA and epidermolysis bullosa: evidence for independent assortment of Weber Cockayne subtype of epidermolysis bullosa and HLA complex. AB - The purpose of this study was to examine the genetic linkage (but not the association) between HLA complex and Weber-Cockayne Subtype of epidermolysis bullosa (EBS-WC). We HLA typed 44 members of three multi-generation families in which 24 members have the clinical evidence of EBS-WC. The patterns of inheritance of various HLA haplotypes and the disease were mathematically analyzed to estimate frequency of recombination (i.e. genetic distance) between HLA complex and the disease by calculating Lod Scores for each family separately as well as all for three families combined. Our results show that only one family had a positive Lod Score. The Lod Scores for the remaining two families as well as the combined Lod Score for all three families were negative. These data suggest that odds are against the genetic linkage between HLA complex and Weber Cockayne Subtype of epidermolysis bullosa and in favor of independent assortment of the disease and HLA complex. PMID- 1878344 TI - Autocrine secretion of an EGF-like substance by a cell line (HSC-1) derived from a human skin squamous cell carcinoma. AB - The presence of EGF-autocrine secretion was investigated in a cell line derived from a human squamous cell carcinoma (HSC-1). The cell line was found to secrete the epidermal growth factor (EGF)-like substance. Meanwhile, normal human and uninvolved and involved psoriatic epidermal cells did not show any evidence of EGF secretion in culture. Not was any evidence of EGF secretion observed in vitro in several malignant cell lines other than HSC-1 derived from human squamous cell carcinomas, adenocarcinoma and melanoma. The addition of EGF did not stimulate, but rather inhibited, the growth of HSC-1 cells in GIT medium as well as Dulbecco's modified essential medium with low concentrations of fetal calf serum (0.5-1%) in vitro. Overexpression of EGF receptors is known to occur in HSC-1. The results suggest that HSC-1 cells exhibit autocrine secretion of the EGF-like substance but not autostimulation in anchorage-dependent cell culture. PMID- 1878345 TI - Proliferation and collagen synthesis by human dermal fibroblasts cultured from different body sites. AB - Distal areas in systemic sclerosis (scleroderma), such as the dorsal skin of the hand are more frequently involved and more indurated than proximal areas. On the contrary, the observation often made after surgical excision or trauma is that distal body areas heal more slowly than proximal areas. A possible explanation may be that dermal fibroblasts from distal body parts are more capable, when stimulated, to synthesize greater or lesser amounts of collagen and proliferate at different rates than dermal fibroblasts from more proximal skin. In this study, cultures of dermal fibroblasts from three different body sites (arm, forearm, and hand) of healthy volunteers were investigated for their proliferative activity and collagen synthesis after stimulation in 3% or 10% fetal bovine serum. No significant differences were observed in cell proliferation or in the relative or absolute collagen synthesis by fibroblasts cultured from the hand, forearm or upper arm. We conclude that other in vivo factors are responsible for the observed differences in fibrosis and healing at different body sites. Moreover, if clonal expansion of different fibroblast phenotypes occurs in these physiologic or disease states, it must be of a magnitude that overcomes the fundamental proliferative and biosynthetic baseline. PMID- 1878346 TI - Immunohistochemical study of lepromin reaction in healthy adults. AB - Lepromin reaction was studied with immunoperoxidase techniques using monoclonal antibodies. The skin reactions were induced by injecting Mitsuda antigen into healthy adults without a family history of leprosy. Both early (48 hours) and late (3 weeks and 2 months) reactions were examined. In the late reaction, focal collections of epithelioid cells had formed, and not only T- but also B lymphocytes were observed around the granuloma. CD1a+ cells were also confirmed to have increased in the late reaction. PMID- 1878347 TI - Abstracts for the XVIth annual meeting of the Japanese Society for Investigative Dermatology. July 10-12, 1991, Nagasaki, Japan. PMID- 1878348 TI - Gold out of lead? The NIH's new "financial management plan". PMID- 1878349 TI - Interleukin-2: counteracting pleiotropy by compartmentalization. AB - Interleukin-2 (IL-2) belongs to a series of mediators that are produced by T cells and exert multiple, pleiotropic effects in an autocrine or paracrine fashion. IL-2 plays a fundamental role in the ontogeny of developing T cells in the thymus and supports the growth or effector function of a wide array of immunologically relevant cells, including macrophages and B and NK lymphocytes, as well as a variety of different T-cell subpopulations. Nonetheless, the function of this lymphokine must be highly controlled in vivo to avoid systemic effects that might endanger the specificity of an immune response and result in autoimmune reactions. Accordingly, various mechanisms guarantee compartmentalization of IL-2, that is, chronological and spatial restriction of IL-2 production, bioavailability, and state of responsiveness. The secretion of IL-2, as well as the expression of the two components of the high-affinity IL-2 receptor (IL-2R), are developmentally controlled during ontogeny and, within the cellular immune system, are restricted to defined pre- and intrathymic stages of immature T cells or T-cell precursors. In the peripheral lymphoid organs, IL-2 is produced by a defined population of mature CD4+ T lymphocytes in which the IL-2 gene is transcribed or silenced, depending on the combination of antigenic and nonspecific activation signals to which the cell is exposed. Thus, the absence of certain costimulatory signals leads to a long-lasting inactivation of the IL-2 gene, a phenomenon that accompanies nondeletional T-cell tolerance. IL-2 has a short half-life and is secreted in apposition to the cell with which the T cell interacts. Expression of the high-affinity IL-2R is activation-dependent in most cell types. Thus, different mechanisms, intervening in all compartments relevant for the action of IL-2, together contribute to a restriction of IL-2 effects, conferring a relative specificity to this pleiotropic mediator. PMID- 1878350 TI - The role of the p50 and p65 subunits of NF-kappa B in the recognition of cognate sequences. AB - An important regulatory element for expression of the MHC class I gene H-2Kb is a palindromic 11-bp enhancer sequence, 5'-GGGGATTCCCC-3', which was shown to interact with the constitutive factor(s) KBF1/H2TF1 and the inducible nuclear factor NF-kappa B, a multisubunit transcription activator. Recent data from molecular cloning and biochemical analyses of KBF1 and NF-kappa B have shown that KBF1 corresponds to the dimerized DNA-binding subunit of NF-kappa B (p50) and that NF-kappa B forms a DNA-binding heterodimer of one p50 and one p65 subunit. In this study, we investigated differences in the binding specificity of the p50 dimer and p50-p65 by using mutants of the H-2Kb motif in binding competition assays. Both forms of NF-kappa B bound with high affinity to a wild-type H-2Kb motif. In contrast to the p50 dimer, p50-p65 had a strongly reduced requirement for an 11th base pair to efficiently recognize the motif. Only in the presence of spermine could the p50 dimer also efficiently bind to motifs altered in positions 1 or 11, suggesting that DNA bending was important for protein-DNA recognition. An H-2Kb motif mutated in one half site such that the frequently found kappa B motif 5'-GGGACTTTCC-3' is created was efficiently recognized only by p50-p65. The decameric kappa B motifs of reduced symmetry, which are most frequently found as cis-acting elements in promoter and enhancer sequences, seem to be bound preferentially by the p50-p65 heterodimer. It thus appears that p65 extends the DNA-binding specificity of NF-kappa B and thereby allows efficient recognition of a wider spectrum of binding motifs. PMID- 1878351 TI - Differential regulation of hepatocyte-enriched transcription factors explains changes in albumin and transthyretin gene expression among hepatoma cells. AB - To investigate the regulation of genes whose expression is enriched in liver we studied expression of the albumin and transthyretin (TTR) genes in a series of rat hepatoma cell lines (FaO, C2, C2rev7, and H5) that express these genes at different rates. The level of expression of albumin and TTR was compared to the expression and DNA-binding activity of four transcription factors, HNF1/LFB1, C/EBP, HNF3, and HNF4, that are found at high concentrations in liver. We conclude that the levels of these factors are controlled both transcriptionally (HNF-3, HNF-4, and C/EBP) and post-transcriptionally (HNF-1/LFB1), and that the cellular concentration of these DNA-binding proteins helps explain the level of transcriptional activity observed for the genes they regulate. PMID- 1878352 TI - Nutrient intakes of different social-class groups: results from the Scottish Heart Health Study (SHHS). AB - Food frequency questionnaire and socio-demographic data were collected from over 10,000 Scottish men and women aged 40-59 years in a cross-sectional study of coronary heart disease (CHD) risk factors. Dietary intake, including the antioxidant vitamins C and E and beta-carotene, was assessed for different socio economic groups. Trends in nutrient intakes were found with social-class (occupational) groups I-V. The non-manual-manual distinctions were clear even after standardizing for serum cotinine, and alternative classification by housing tenure and level of education did not confound the social-class effect. Total energy intake was significantly higher in the manual (men 10,363 KJ, women 7507 KJ) than in the non-manual (men 9156 KJ, women 7169 KJ) groups, and all nutrient amounts except for vitamin C, vitamin E, beta-carotene and fibre were significantly higher in the manual than the non-manual groups. Alcohol intake was lower in manual women, but higher in manual men compared with their respective non-manual groups. Sex and social-class differences were maintained after adjusting for total energy. Women in general, and manual women in particular, had the highest percentage energy from total fat (40.2) and saturated fat (18.2), while the percentage energy from polyunsaturated fat was lower in men than women, and lowest in manual men (4.4). The polyunsaturated:saturated fat (P:S) ratios were, for non-manual and manual men 0.32 and 0.31, and for non-manual and manual women 0.31 and 0.28. Fibre and antioxidant vitamin intakes, when expressed as nutrient densities, were lower in men than women, and lowest in manual men. Overall, men and women in manual occupations had a poorer-quality diet than did those in non-manual occupations. The coincident low P:S ratios and low antioxidant vitamin intakes in manual groups may contribute to an increased risk of CHD. Thus, the findings are compatible with the view that poor diet may be a contributory factor to the higher mortality rates for CHD which occur in the lower socio-economic groups. PMID- 1878353 TI - Antioxidant vitamin intakes assessed using a food-frequency questionnaire: correlation with biochemical status in smokers and non-smokers. AB - The increasing interest in the possible role of antioxidant vitamins in many disease states means that methods of assessing vitamin intakes which are suitable for large-scale investigations are now required. The suitability of the food frequency questionnaire, which was developed by the Medical Research Council - Cardiff Group, for determining dietary intake of antioxidant vitamins in epidemiological studies was investigated in 196 Scottish men. The validity of the dietary data was assessed by comparison with serum vitamin concentrations, and separate analyses were performed for current smokers and non-smokers. The results showed that total energy intake and the percentage of energy derived from sugar were higher in smokers, and that both dietary and serum values of vitamin C, beta carotene and vitamin E were lower in smokers than non-smokers. After adjustment for serum lipids, energy intake and body mass index, correlation coefficients between dietary and serum vitamins C and E were similar for smokers (r 0.555 and 0.25 respectively) and non-smokers (r 0.58 and 0.32 respectively). Correlation between dietary and serum carotenes was reduced from 0.28 in non-smokers to 0.09 in smokers and correlations for retinol and total vitamin A were weakly significant only for non-smokers. The food-frequency questionnaire assigned greater than 70% of subjects correctly into the upper or lower plus adjacent tertiles of serum vitamin values, with the exception of beta-carotene and total vitamin A for smokers. Thus, the food-frequency questionnaire appeared to be an adequate tool for assigning individuals into tertiles of serum antioxidant vitamins with the main exception of beta-carotene for smokers. Marked differences do occur between the vitamins and between the smoking groups which may reflect reduced accuracy of reporting on the food-frequency questionnaire or differential absorption and metabolism of the vitamins. PMID- 1878354 TI - The effect of nutritional intake on outcome of pregnancy in smokers and non smokers. AB - The relationship between nutrient intake and pregnancy outcome (adjusted birth weight and gestational age) was investigated in randomly selected non-smokers (n97) and in heavy smokers (15 + cigarettes/d) (n72) booking for ante-natal care at a hospital in South London. Weighted dietary intakes (7d) were obtained at 28 and 36 weeks gestation. Birth weight was adjusted for gestational age, maternal height, parity and sex of infant. Compared with non-smokers, intakes of micronutrients and fibre were lower in smokers at both 28 and 36 weeks, and smokers reduced their intakes more in late pregnancy. The babies of smokers had a lower adjusted birth weight but there was no difference in length of gestation between smokers and non-smokers. After controlling for smoking, social class and alcohol consumption, nutrient intakes at 28 weeks were found to have no effect on adjusted birth weight. However, intakes of protein, zinc, riboflavin and thiamin at 36 weeks, and the change in intakes of these nutrients (plus iron) between 28 and 36 weeks, had independent positive effects on birth weight. Some of the effect of smoking on birth weight appeared to be mediated through differences in nutrient intakes. Smoking explained 14.3% of the variance in birth weight in this population and a further 2.4-7.2% was explained by change in nutrient intakes between 28 and 36 weeks. It is recommended that women in pregnancy do not reduce their dietary intakes in late pregnancy. PMID- 1878355 TI - The efficiency of chewing during eating and ruminating in goats and sheep. AB - The total amounts of time spent eating and ruminating per 24 h by goats and sheep were determined. The efficiencies of chewing during eating (mean value of C.EAT) and chewing during ruminating (mean value of C.RUM) on the breakdown of feed particles to below the critical size required to leave the rumen (less than 1.0 mm) were investigated. All studies were done with the animals fed on a chaffed lucerne (Medicago sativa) hay diet. Goats spent more time eating (+3.1 h; P less than 0.01), and less time ruminating (-2.2 h; P less than 0.05) per 24 h, than sheep, when fed hourly at ad lib. intake. The efficiency of chewing during eating (mean value of C.EAT) in breaking down feed particles to less than 1.0 mm was greater in goats (85%; P less than 0.01) than sheep (48%). The process of rumination in sheep served to reduce the feed particles which were greater than 1.0 mm in the rumen to less than 1.0 mm. Sheep tended to be more efficient in this process than goats (59 v. 48%), with the difference not attaining significance (P greater than 0.1). The greater frequency of chews (number of total jaw movements/min) during eating in goats (P less than 0.01), or during ruminating in sheep (P less than 0.001), was the major component explaining differences in efficiency between the two species in both the eating and rumination processes. When corrected for the number of chews/min, the differences in mean value of C.RUM and mean value of C.EAT were not significant between goats and sheep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878356 TI - The effect of a nutritionally-balanced cassava (Manihot esculenta Crantz) diet on endocrine function using the dog as a model. 1. Pancreas. AB - Growing dogs were divided into three groups and were fed on a control (rice) diet, a diet in which cassava (Manihot esculenta Crantz; gari) was used as the carbohydrate source, and the rice diet to which cyanide (equivalent to that present in gari) was added. Each group consumed its diet for 14 weeks, during which plasma thiocyanate concentration and plasma lipase (EC 3.1.1.3) activity were monitored. Plasma free amino acids were determined from pooled samples taken at the end of the experimental period, and the insulin status of the dogs was evaluated using the gluconeogenic index. The dogs were killed and the pancreas examined for histopathology. Dogs fed on both gari diet and the rice + cyanide diet generated significant amounts of thiocyanate when compared with the controls, with the rice + cyanide group having higher plasma thiocyanate than the gari group (P less than 0.01). Plasma lipase activity rose significantly at the end of the experimental period in the dogs fed on gari (P less than 0.05). Gluconeogenesis from protein was greatest in the dogs fed on gari, five times greater than that in the control dogs, while gluconeogenesis from protein in the dogs fed on rice + cyanide was approximately twice as high as that of the control dogs. Histopathological examination of the pancreas showed haemorrhage, necrosis, fibrosis and atrophy of the acinar tissue and fibrosis of the islets of Langerhans in the dogs fed on gari. The pancreas of the dogs fed on rice + cyanide showed similar lesions but haemorrhage was not prominent and fibrosis was more marked.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878357 TI - The effect of a nutritionally-balanced cassava (Manihot esculenta Crantz) diet on endocrine function using the dog as a model. 2. Thyroid. AB - Growing dogs were divided into three groups and were fed on nutritionally balanced diets. Control dogs were fed on a rice diet, the cassava (gari) group ate a diet in which gari provided the carbohydrate source, while the rice + cyanide group consumed the rice diet to which hydrocyanic acid (equivalent to that present in gari) was added. Each group consumed its diet for 14 weeks, during which plasma thiocyanate concentration and total serum triiodothyronine (T3) were monitored. At the end of the experiment the concentrations of the plasma free amino acids phenylalanine and tyrosine, the thyroid weights and histology were determined. While plasma thiocyanate remained undetectable in control dogs, animals consuming both gari and rice + cyanide generated significant amounts. In the control dogs and the gari group, total serum T3 increased 40 and 38.8% respectively from the basal level by the end of the period (P less than 0.02). In contrast there was a decrease in T3 by 36% in the dogs fed on rice + cyanide (P less than 0.05). This group also showed significant thyroid enlargement and a histological picture consistent with parenchymatous goitre, whereas the gari group was essentially normal. The relatively low mean thyroid weight, the rise in total serum T3 level and the normal histological appearance of the gland indicate that dogs that consumed the gari diet were essentially normal with respect to their thyroid function, in spite of their high blood thiocyanate content. In contrast, dogs that consumed rice with cyanide suffered from hypothyroidism and goitre.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878358 TI - Plasma 65Zn kinetics in the rat. AB - The amount of 65Zn in the plasma of rats after intravenous injection was found to decline following closely two-compartment kinetics over a period of 90 min. Comparative analysis of the amount of 65Zn present in the two kinetic pools at various time-intervals post-injection with the actual physiological location of the 65Zn, revealed that the initial pool (Qa) is primarily the blood plasma, while the second pool (Qb) is primarily within the liver. The plasma Zn concentration and Qa were both found to fall reproducibly during Zn depletion, whereas Qa and Qb increased following injection of Escherichia coli endotoxin in contrast to the decline in plasma Zn concentration. Further investigation of the nature of Qb indicates that it represents in part a metabolic pool within the liver which varies substantially in response to Zn status in a manner similar to metallothionein. PMID- 1878359 TI - Iron absorption during normal human pregnancy: a study using stable isotopes. AB - The absorption of iron has been determined in nine healthy women studied serially during pregnancy and once post delivery. Following the oral administration of 5 mg aqueous 54FeSO4 plus ascorbic acid and the intravenous injection of 200 micrograms 57FeSO4, the isotope ratios of 54Fe: 56Fe and 57Fe: 56Fe in serum were measured by the use of inductively-coupled-plasma mass spectrometry whereby metal ions are vaporized into an argon plasma without previous blood sample preparation. Mean oral Fe absorption was 7.6 (range 1-22)% at 12 weeks gestation, 21.1 (range 9-58)% at 24 weeks, 37.4 (range 18-56)% at 36 weeks and 26.3 (range 8 54)% at 12 weeks post delivery. All the other biochemical and haematological indices were within normal limits for pregnancy. The significant increase (P less than 0.01) in Fe absorption during normal pregnancy suggests that most women would have the potential to meet the Fe demands of pregnancy without the need for supplementation if dietary Fe has similar availability to the aqueous preparation. PMID- 1878360 TI - Disposition kinetics and dosage regimen of vitamin E administered intramuscularly to sheep. AB - Three experiments were conducted to estimate the effects of single intramuscular (IM) administrations of vitamin E on blood plasma and tissue concentrations of alpha-tocopherol in sheep. In Expt 1, plasma kinetics of alpha-tocopherol in sheep (n 30) were investigated following IM administration of three doses (ten sheep/dose) of DL-alpha-tocopheryl acetate, (20, 40 and 60 mg/kg live weight). Plasma profiles of alpha-tocopherol consisted of a lag phase followed by an apparent first-order absorption and elimination phase. The rate of absorption and elimination, as well as the lag phase, were independent of the dose, but the extent of absorption was directly proportional to dose. In Expt 2 (eighteen experimental and five control sheep), the animals were injected as in Expt 1 and were killed at 0, 80 and 176 h. Increases in alpha-tocopherol levels in organs were much higher than in plasma. Some tissues such as liver, spleen, lung and adrenal appeared to exhibit rapid absorption and elimination phases. The amount absorbed was proportional to the dose administered. Other organs such as heart, kidney and pancreas had a slow elimination rate. In Expt 3, D-alpha-tocopherol was injected IM into ten sheep at either 604 mg or 1208 mg. The mean hepatic alpha-tocopherol concentrations in both groups rose rapidly and after 4 weeks of dosing its concentrations were higher than the predosing levels. The increase in hepatic tocopherol concentrations were higher following 1208 mg dosing than 604 mg D-alpha-tocopherol. No simple relationship existed between plasma and hepatic alpha-tocopherol concentrations. This suggests a difference in body mechanisms controlling vitamin E in blood and liver. PMID- 1878361 TI - Riboflavin deficiency in the rat: effects on iron utilization and loss. AB - Iron absorption and daily loss of Fe were measured in riboflavin-deficient (B2-) Norwegian hooded rats and controls (B2+). Animals were fed on a test meal extrinsically labelled with 59Fe and whole-body radioactivity measured for 15 d. Riboflavin deficiency led to a reduction in the percentage of the 59Fe dose absorbed and an increased rate of 59Fe loss. All post-absorption 59Fe loss could be accounted for by faecal 59Fe, confirming that the loss was gastrointestinal. Fe concentrations and 59Fe as a percentage of retained whole-body 59Fe were higher in the small intestine of riboflavin-deficient animals than their controls, 14 d after the test meal. A separate experiment demonstrated that riboflavin deficiency was associated with a significant proliferative response of the duodenal crypts of the small intestine. These observations may explain the enhanced Fe loss in riboflavin deficiency. PMID- 1878362 TI - Carrageenan-induced granuloma and iron status in rats with dietary polyunsaturated fatty acid deficiency. AB - Sprague-Dawley rats were fed for 4 months on a control diet or a polyunsaturated fatty-acid (PUFA)-deficient diet. The combined effects of iron overload (Fe dextran) or Fe deficiency (desferrioxamine) on carrageenan-induced granuloma were studied. PUFA deficiency induced changes in Fe metabolism, but no alterations in lipid peroxidation variables were observed. Inflammation implied an increase in lipid peroxidation, Fe storage and caeruloplasmin concentration, together with symptoms of anaemia. PUFA deficiency in inflamed rats gave rise to a lower inflammatory response (granuloma weight and prostaglandin E2 concentration) and ethane exhalation. Fe overload potentiated inflammatory and lipid peroxidation processes, whereas Fe deficiency decreased them. PMID- 1878363 TI - Issues relating to nutrient analysis. PMID- 1878364 TI - Membrane vesicles in the study of transport processes: a critical analysis of the experimental procedure. AB - A critical analysis of the use of membrane vesicles in the study of cotransport processes is presented. Transport experiments were simulated according to two different models, stressing those conditions that seemed more relevant in affecting the measurements. In particular, we observed that the experimental Vmax values were underestimated. This underevaluation depended on the incubation time employed to measure the initial uptake rate and on the time necessary to wash the vesicles. Also the temperature and the composition of the washing solution, together with the Q10 of the transport process taken into consideration, had a consistent influence on the uptake. All the above mentioned effects were affected by the vesicle volume: the smaller the volume, the greater the underestimate of the uptake. This theoretical analysis underlines, on the one side, that the experimental data should be interpreted with some caution, on the other, that the examined procedure allows an internal check of its validity by adopting suitable simulations of the experiments. The use of the presented models as a tool for the planning and the critical analysis of the experimental results is suggested. PMID- 1878365 TI - Influence of phloretin and alcohols on barrier defects in the erythrocyte membrane caused by oxidative injury and electroporation. AB - Oxidative damage by diamide, periodate and oxygen-derived reactive species, but also exposure to electroporation induce in the erythrocyte membrane dynamic, presumably fluctuating, defects having the properties of aqueous holes with definable radii and selectivities. These leaks, which can be quantified by measuring tracer fluxes or rates of colloid-osmotic lysis, are here shown to be inhibited by phloretin and a small number of related phenol compounds (phenolphthalein, hydroxyacetophenones, nitrophenol), while a host of other 'membrane-active' agents is not effective in this respect. I50 values range from about 200 microM for phloretin and phenolphthalein to about 10 mM for 4 nitrophenol. Inhibition by phloretin is reversible, not competitive and not related in its extent to the extent of leakiness. In contrast, the enhancement of transbilayer mobility of amphiphilic lipid probes, which invariably goes along with leak formation of the type described, is not affected by phloretin. Aliphatic alcohols (hexanol, butanol) have an amplifying effect on leaks induced by oxidative damage but do not affect leaks induced by electroporation. The alcohol-amplified leaks maintain the properties of aqueous holes as indicated by a low activation energy of leak fluxes. Since both, inhibition and stimulation of leak fluxes do not go along with appreciable changes of the apparent radii of the aqueous holes, changes in the dynamics (opening and closing) of the defects are proposed to underly the effects of phloretin and alkanols. The membrane lipid domain is likely to be the site of the leaks and of their modulation. PMID- 1878366 TI - pH-dependent lipid packing, membrane permeability and fusion in phosphatidylcholine vesicles. AB - We have studied the rate of membrane fusion, the lipid dynamics and order and the membrane permeability of phosphatidylcholine vesicles as a function of pH. Acidification induced very different effects depending on the state of the bilayer. In liquid-crystalline bilayers, acidification decreased the rate of membrane fusion, the acyl chain motion and disorder and the rate of K+ release, whereas in solid bilayers acidification increased the rate of membrane fusion, the lipid acyl chain disorder and the rate of K+ release. These pH-dependent modifications are interpreted in terms of conformational and/or packing changes of the phosphatidylcholine head group in the membrane. In solid bilayers, these changes are not easily accommodated by the rigid structure, and the resulting stress leads to an unstable bilayer. PMID- 1878367 TI - Changes of the compositional asymmetry of phospholipids associated to the increment in the membrane surface potential. AB - The contribution of phosphatidylinositol (PI) and phosphatidylserine (PS) to the outer negative membrane surface potential was studied in normal, PS-rich and PI rich yeast cells. Under carefully defined conditions; PS and PE were quantified by using the non-penetrating chemical probe trinitrobenzenesulfonic acid (TNBS) and the PI by degradation with a specific phospholipase C. An asymmetric distribution of phospholipids in the plasma membrane with more PS (80-90%), PI (70-85%) and PE (70-85%) in the inner leaflet was found. When compared to normal cells there were 3-times more PI and 2-times more PS in the outer leaflet of the PI-rich and PS-rich cells. These values are consistent with the two-times increased surface potential in these cells. Interestingly, the contribution of PI was around twice the contribution of PS to the surface potential in the cells studied. When compared to normal cells there was a two-times increased accessibility of PS to TNBS in the PI-rich cells and the accessibility of PI to phospholipase C was also increased two-times in the PS-rich cells, while the proportion of derivatized PE was similar in all cells. Taking into account that the amount of PI is similar in normal cells and PS-rich cells and the amount of PS is similar in PI-rich cells and normal cells, a charge driven transbilayer transport of acidic phospholipids can be proposed. PMID- 1878368 TI - Uptake and endocytic pathway of transferrin and iron in perfused rat liver. AB - Uptake and distribution of transferrin and iron in perfused rat liver are dependent on perfusion temperature, time and uptake affinity. Transferrin passes at least two different compartments on its receptor-mediated recycling pathway, which are separable by centrifugation in a shallow Nycodenz gradient. Perfusion at lowered temperature (16 degrees C) is sufficient for internalization of transferrin and iron. Passage of radiolabelled iron to other than endosomal compartments as well as recycling of labelled transferrin are largely suppressed at this perfusion temperature, as much less is released by further perfusion with unlabelled transferrin than at 4 degrees C where the ligand is largely washed off the surface, or 37 degrees C, where the recycling pathway is operating. But also at lowered temperature only a part of the iron in endosomal fractions can be assigned to transferrin. A considerable part of the total uptake of transferrin and iron can be attributed to low-affinity mechanisms even at very low transferrin concentrations. Transferrin receptors are concentrated in endosomal fractions in comparison to fractions representing different plasma membrane domains of the liver. Endosomal fractions specifically display detergent activated NADH-acceptor oxidoreductase which may be part of the iron uptake system. PMID- 1878369 TI - Phase transition of dimyristoylphosphatidylglycerol bilayers induced by electric field pulses. AB - The phase transition of dimyristoylphosphatidylglycerol (DMPG) bilayers has been studied by measurements of light scattering under high electric field pulses. Midpoints of phase transitions have been identified by a clear discontinuity of field induced relaxation amplitudes. We show that the phase transition of DMPG suspensions in monovalent salt is virtually independent of the electric field strength up to approx. 35 kV/cm. A shift of the lipid phase by electric field pulses has been observed, however, for DMPG suspensions in the presence of Ca2+ ions. DMPG suspensions exhibit a jump of the phase transition temperature from 17 degrees C at Ca/DMPG molar ratios r less than 1/7 to 32 degrees C at r greater than 1/7. Field pulses of 60 to 100 microseconds applied to DMPG suspensions with Ca2+ at r greater than 1/7 induce discontinuities of relaxation amplitudes in the temperature range 15 to 22 degrees C in addition to the 'standard' one at 32 degrees C, when the electric field strength is above 15 kV/cm. These results indicate that electric field pulses induce a transition from the phase formed at 'high' Ca(2+)- to the one formed at 'low' Ca(2+)-ion concentrations. Our results are consistent with a dissociation field effect on Ca(2+)-lipid complexes which drives the phase transition. PMID- 1878370 TI - A study on peroxidative damage of the porcine intestinal brush-border membranes using a fluorogenic thiol reagent, N-(1-pyrene)maleimide. AB - To examine the effects of lipid peroxidation on the protein conformation in the porcine intestinal brush-border membranes, a fluorogenic thiol reagent, N-(1 pyrene)maleimide (NPM) was employed. By treatment of NPM-labeled membranes with 100 microM ascorbic acid/10 microM Fe2+ in the presence of various concentrations of tert-butyl hydroperoxide (t-BuOOH), the fluorescence intensity of the complex decreased with the formation of conjugated diene, depending on the hydroperoxide concentration. The temperature dependence profile of the fluorescence intensity of NPM-labeled control membranes showed a thermal transition of the NPM fluorescence at 27-28 degrees C. The transition phenomenon of the NPM fluorescence in the membranes around this temperature disappeared by treatment of the labeled membranes with 100 microM ascorbic acid/10 microM Fe2+/0.6 mM t BuOOH. The difference in response of the fluorescence characteristics of the bound NPM for temperature variation between the control and peroxidized membranes was also observed in the quenching efficiency with acrylamide. Measurement of the fluorescence polarization revealed that the harmonic mean of the rotational relaxation times of the bound NPM molecules to the membrane proteins increased from 1.96 to 4.93 microseconds by lipid peroxidation of the membranes. This indicates that the movement of the region containing NPM-labeled SH groups in the membrane proteins is restricted by lipid peroxidation. Treatment of NPM-labeled peroxidized membranes with sodium dodecyl sulfate (SDS) resulted in a restoration of the intensity of the NPM fluorescence to the level of the control ones. In addition, the temperature dependence profile of the fluorescence intensity of NPM labeled peroxidized membranes in the presence of SDS also showed an appearance of a transition phenomenon around 30 degrees C. The result of SDS-polyacrylamide gel electrophoresis of the peroxidized membranes revealed that high-molecular-weight aggregates of the membrane proteins were not formed by lipid peroxidation. On the basis of these results, changes in the environmental properties around NPM labeled SH groups in the membrane proteins by lipid peroxidation are discussed. PMID- 1878371 TI - Comparisons of steady-state anisotropy of the plasma membrane of living cells with different probes. AB - We have used an extended Perrin equation which was in agreement with literature data for steady-state anisotropy (rSS) for a wide variety of artificial and isolated biological membranes labeled with various probes (Van der Meer et al. (1986) Biochim. Biophys. Acta 854, 38-44 to obtain the static component (r infinity) for the intact plasma membranes of living cells. We show that lipid structural order parameters can be obtained for DPH and TMA-DPH in the plasma membranes of intact cells. We have examined the relationship between 'fractional limiting hindered anisotropy', r infinity/r0, which is related to the lipid structural order parameter, of DPH, TMA-DPH, DPHpPC, and a series of depth dependent probes (n-(9-anthroyloxy) fatty acids, with n = 2-16), using data from 19 cell types. There was a linear relationship between r infinity/r0 values of DPH and TMA-DPH, but the relationship between either of these probes was non linear with respect to DPHpPC or the series of fatty acid probes. The relationship between r infinity/r0 values of DPHpPC and the series of fatty acid probes was linear, suggesting that they not only undergo similar motions in the membrane, but also experience similar types of restriction to motion, a type which is different from that experienced by DPH and TMA-DPH. We show that for the plasma membranes of living cells, 'second degree' order parameters can be estimated for DPH and TMA-DPH, and propose that the parameter r infinity/r0, or the 'fractional limiting hindered anisotropy', analogous to a 'first degree' order parameter, can be estimated for DPHpPC and the depth-dependent fatty acid probes to evaluate the density of membrane packing. PMID- 1878372 TI - Active and monomeric human red cell glucose transporter after high performance molecular-sieve chromatography in the presence of octyl glucoside and phosphatidylserine or phosphatidylcholine. AB - The human red cell glucose transporter (Glut 1) was purified by ion-exchange chromatography in the presence of octyl glucoside. The state of association of the protein was studied, and the transport activity was determined after exchange of copurified membrane lipids for phosphatidylserine (PS) or phosphatidylcholine (PC). The purpose was to analyze the Glut 1 preparation for homogeneity and activity prior to attempts at crystallization. Analyses by high performance molecular-sieve chromatography showed that the Glut 1 was monomeric immediately after the ion-exchange purification: the Mr of the Glut 1 polypeptide was estimated to be 49,000 +/- 6000 by TSKgel G3000SW chromatography monitored by low angle laser light-scattering photometry, differential refractometry and UV photometry. This required determination of the absorption coefficient of the Glut 1, which was measured to be 1.13 +/- 0.03 ml mg-1 cm-1 at 280 nm, referring to the polypeptide concentration. The Mr value is consistent with the cDNA-deduced Mr 54,117 of the very similar HepG2 glucose transporter polypeptide. At 2 degrees C, pH 7 and an ionic strength of 0.06 M, the Glut 1 associated gradually during three days to form oligomers. These formed much more rapidly at room temperature or at high ionic strength. Freshly prepared Glut 1 retained high activity after separation from membrane lipids on a TSKgel G3000SW column in the presence of 40 mM octyl glucoside and 1 mM PS or PC. In contrast, most of the activity was lost when the membrane lipids were separated from the protein in the absence of eluent lipids. The presence of a phospholipid was thus essential for retention of high activity of the Glut 1 in octyl glucoside and PC was nearly as effective as PS. PMID- 1878373 TI - Purification of a K(+)-channel protein of sarcoplasmic reticulum by assaying the channel activity in the planar lipid bilayer system. AB - A K(+)-channel protein of the sarcoplasmic reticulum (SR) was purified by assaying the channel activity in a planar lipid bilayer system. The light fraction of SR vesicles was solubilized in 3-[(3-cholamidopropyl)dimethylammonio] 1-propanesulfonate (CHAPS) and fractionated by an anion-exchange chromatography and followed by gel filtration chromatography and affinity chromatography with concanavalin A. All fractions in each steps were mixed with asolectin solubilized in CHAPS and reconstituted into vesicles by dialysis. The channel activity of each fraction was assayed after the reconstituted vesicles had been fused into a planar lipid bilayer. The final fraction which showed the K(+)-channel activity contained only 100 kDa protein in a silver-stained gel after SDS-PAGE and an anti Ca(2+)-ATPase antibody did not recognize the protein. The characteristics of the K(+)-channel were identical to those observed in native SR vesicles when using the same method. The channel showed a single-channel conductance of 120 pS in 0.1 M KCl and marked voltage dependence. The channel did not permeate Ca2+ and Cl- and was blocked by neomycin B. PMID- 1878374 TI - Comparative electrophysiological study of reconstituted giant vesicle preparations of the rabbit skeletal muscle sarcoplasmic reticulum K+ channel. AB - Sarcoplasmic reticulum (SR) membranes isolated from rabbit skeletal muscle were reconstituted into two types of giant vesicles: (1) Giant proteoliposomes prepared by freeze-thawing of a mixture of SR vesicles and sonicated phospholipid vesicles without the use of detergent. (2) Giant SR vesicles prepared by fusion of SR vesicles using poly(ethylene glycol) (PEG) as a fusogen and without the addition of exogenous lipid. These giant vesicles were patch-clamped and properties of the single voltage-dependent potassium channel in the excised patch were studied. Single-channel conductance in a symmetrical solution of 0.1 M KCl and 1 mM CaCl2 was 140.0 +/- 10 pS (n = 5) for freeze-thawed vesicles and 136.4 +/- 15 pS (n = 7) for PEG vesicles. Both types of vesicles exhibited a sub conductance state having 55% of the fully open state conductance. The voltage dependence of open-channel probability could be expressed in terms of thermodynamic parameters of delta Gi = 0.95 kcal/mol and z = -0.77 for freeze thawed vesicles and delta Gi = 0.92 kcal/mol and z = -0.87 for PEG vesicles. These values correlated well with previous data obtained by fusion of native SR vesicles with a planar lipid membrane. Channel orientation was found to be conserved in both types of vesicles used in the present study. PMID- 1878375 TI - The effects of density fluctuations on the partitioning of foreign molecules into lipid bilayers: application to anaesthetics and insecticides. AB - An extensive computer-simulation study is performed on a simple but general molecular model recently proposed (Jorgensen et al. (1991) Biochem. Biophys. Acta 1062, 277-238) to describe foreign molecules interacting with lipid bilayers. The model is a multi-state lattice model of the main bilayer transition in which the foreign molecules are assumed to intercalate at interstitial lattice positions. Specific as well as non-specific interactions between the foreign molecules and the lipid acyl chains are considered. Particular attention is paid to the fluctuating properties of the membrane and how the presence of the foreign molecules modulates these fluctuations in the transition region. By means of computer-stimulation techniques, a detailed account is given of the macroscopic as well as microscopic consequences of the fluctuations. The macroscopic consequences of the fluctuations are seen in the thermal anomalies of the specific heat and the passive trans-membrane permeability. Microscopically, the fluctuations manifest themselves in lipid-domain formation in the transition region which implies an effective dynamic membrane heterogeneity. Within the model it is found that certain anaesthetics and insecticides which are characterised by specific interactions with the lipids have a strong effect on the heterogeneity of the membrane inducing regions of locally very high concentration of the foreign molecules. This leads to a broadening of the specific heat peak and a maximum in the membrane/water partition coefficient. These results are in accordance with available experimental data for volatile general anaesthetics like halothane, local anaesthetics like cocain derivatives, and insecticides like lindane. PMID- 1878376 TI - Evidence for the activity of a phospholipid exchange protein in vivo. AB - Liposomes containing a self quenching concentration of a fluorescent phosphatidylethanolamine analog, were microinjected into Chinese hamster ovary cells. Immediately after microinjection, little intracellular fluorescence was observed. 10 min post-injection, labeling of the nuclear envelope and mitochondria became evident. Combined with control studies, our results suggest that phospholipid exchange protein(s) facilitates phosphatidylethanolamine movement in vivo. PMID- 1878377 TI - [Film-screen combinations for mammography]. AB - Optimizing and standardizing mammography as well as its quality assurance are gaining in importance with regard to the screening programmes that are being initiated for the early detection of breast cancer. In Germany, the guidelines of the Bundesarztekammer, the directives implementing section 4 and section 16 of the Rontgenverordnung and the standards DIN 6868, Part 7 and 52 are available. The data in these standards concerning tolerances and guide values for physical variables of the imaging system are only partially consistent. This also applies to the comparison with the document "Quality criteria for x-ray exposures in medical diagnostics" of the Commission of the European Communities. The different statements concerning the switch-off value of the dose in particular, reflect an uncertainty as to how unsharpness and noise of the image receptor impair the medical value of the images. With regard to the increased demands for visual resolution capacity, it can be stated that the "Medical quality requirements" and the "Radiographic guide-lines" harmonize with one another only inadequately. Contrast is one of the most important image quality parameters in mammography. Practically no statement is made on this in the available documents. One reason for the present unsatisfactory situation is certainly the especially high demands placed on image quality in mammography. In the present paper, these points of criticism are discussed in detail and proposals for closer specification and better delineation of the physical image quality parameters are submitted. PMID- 1878378 TI - [A modified radiographic technique for the x-ray study of the paranasal sinuses]. AB - A cassette frame holder enabling two partial radiograms of the paranasal sinuses in different projections on a single x-ray film is described. PMID- 1878379 TI - [Genetic injuries caused by radiation and other harmful environmental pollutants]. AB - Cancer may be induced by chemicals, ionizing radiation and certain viruses. The first causal relationships between occupation and increase in cancer have been reported two and half centuries ago. In the meantime, many other occupational toxicants have been identified as cancer inducing agents. However, quantitative risk estimates can be established in a few cases only. On the other hand, modern epidemiological investigations have brought about the main causes of cancer in highly civilized populations as certain life-styles; approximately 35% are attributed to inadequate diet and nutrition, 30% to tobacco, 7% are hormone related in context with human reproduction, 4% due to occupational exposures, 3% may be caused by alcohol consumption, 1,5% by UV radiation and 1% by medicines (cytostatics included). Cancer risks from radiation exposure are comparatively very low. Although radiation can be measured precisely and reliably as physical units, cancers induced by nuclear weapon fallout and precipitation from the accident of Chernobyl will never be detected by epidemiological methods due to their minimal proportions. The attribution of causes obtained in this way allows for the conclusion: human cancers are mostly due to chemically definable factors, and thus are avoidable. PMID- 1878380 TI - [Balloon dilatation and local thrombolysis in massive pulmonary embolism--initial results of a new therapy concept]. AB - The high mortality rate among patients suffering from massive pulmonary embolism makes it imperative to act quickly. The first and foremost goal must be to lower the pulmonary pressure rapidly and to relieve the right ventricle. In three patients with massive pulmonary embolism we therefore tried to crush the thrombus by means of a balloon catheter. The diameters of the balloons were adapted to the size of the vessels to be treated; the balloon diameters were between 10 and 20 mm. Recanalisation resulted in a rapid improvement of perfusion and haemodynamic relief of the right ventricle. This was clinically documented by the drop in pulmonary pressure levels and an impressive improvement of general well-being. Dilation was followed by thrombolytic therapy adapted to the relevant situation. This method of thrombus crushing by means of balloon catheters is indicated in case if massive thrombi in the main stem of the a. pulmonalis, with elevated pulmonary pressure levels, and corresponding clinical signs and symptoms. It can follow alternatively as a first possibility of pressure relief directly after diagnostic pulmangiography. The initial clinical results of this new treatment method are most encouraging. Complications have not been observed so far. PMID- 1878381 TI - [Thoracic intervertebral disk prolapse--the place of imaging procedures]. AB - MR tomography is now considered to be the examination method of choice in diagnosis of thoracic vertebral disk prolapses, since all the other imaging methods do not lend themselves easily to this task. The advantages of MR are that it is non-invasive, that the soft parts yield strong contrasts, and that multiplanar sections are possible; sagittal section is particularly useful in the preoperatively important correct localisation of the height. CT proved of equal value only in calcified disk prolapse. However, since calcification does not entail any additional therapeutic consequences, MR can be used in this case too as a leading imaging method. If MR can be applied, myelography and myelo-CT should be set aside. PMID- 1878382 TI - [Sonographic findings in trauma-induced liver injuries]. AB - In 12 of 49 patients operated on for liver injuries we performed sonographic examination of the abdomen on admission to hospital within the framework of emergency diagnostics. The most sensitive finding was the identification of the presence of intraabdominal free fluid. The liver injury itself was sonographically diagnosed in only 5 patients. Sonographically, an additional injury of the spleen was found in 2 of 3 patients; in one patient it was possible to detect an injury of the kidney. PMID- 1878383 TI - [Atypical bone metastases in prostate cancer]. AB - Two cases of prostatic cancer with single bone metastasis in the tibia are discussed. The intense uniform involvement of a solitary limb bone with high perfusion and blood pool activity in the 3-phase bone scan and the positive white blood cell scan (observed in one case) were not typical for a metastatic bone lesion. Conventional radiomorphology--lamellar, periosteal reaction, disseminated medullar sclerosis, no localized lesion--also led to other differential considerations such as osteomyelitis and malignant lymphoma, which could not be specified by CT and MRI. Even if there is no typical morphology in scintigraphic and radiologic imaging, biopsy should be performed to exclude bone metastasis in prostatic cancer. PMID- 1878384 TI - [Diagnostic imaging and treatment of an invasive thymoma together with myasthenia gravis]. AB - A 40-year old woman with an invasive thymoma and myasthenia gravis is described in this article. Chest-x-ray, CT and MRI of the mediastinum could not offer definite results on tumour malignancy. Radical surgical removal was the consequence. This revealed a tumour infiltration of the pleura and pericardium; hence an adjuvant irradiation must have been performed. Mestinon--treatment was afterwards gradually reduced. PMID- 1878385 TI - [Observations on the same or different conditions as the cause of the same or different overload damage]. AB - Under identical conditions, the same changes develop if the spinal column is overstrained/overburdened. Under varying conditions, varying changes develop if the spinal column is overstrained/overburdened. Conversely, on presentation of an x-ray conclusions can be drawn from which conditions the changes have resulted. PMID- 1878386 TI - [Digital archiving and communication in hospitals]. AB - Different concepts and already available components of a HIS (Hospital Information System) for archiving all data in a hospital are described. Using the example of the Kiel University Hospital, it is shown that a complete HIS-system can be made from already commercially available components. PMID- 1878387 TI - [Techniques, results and risks of chemoembolization of malignant liver tumors]. AB - This is a report on 55 chemoembolizations (ChE) in 31 patients with primary (n = 10) and secondary (n = 21) liver malignomas. Probing of the segmental arteries was always possible by means of a coaxially placed 3F catheter system. Chemoembolization was effected with a mixture of ivalon particles, 20 mg mitomycin or 40-60 mg epirubicin and an ethibloc solution. More than 75% of the patients showed a decrease in tumour size and/or tumour density. The proportion of surviving patients was 80.6% after 6 months. Within this period, extrahepatic metastases were seen for the first time in 19.4% of the patients. References in literature on techniques and results of chemoembolization are discussed. PMID- 1878388 TI - Three-dimensional imaging of the anal sphincter: a new approach to anorectal manometry. AB - Anorectal dysfunction can be an extreme embarrassment and inconvenience to persons afflicted with the condition, disrupting their lifestyle. Evaluation of the anal sphincter and the distinction between muscular and neural etiology is essential. Three-dimensional imaging of the anal sphincter by use of anorectal manometry with an eight-port perfused catheter combined with computer analysis aids in defining anal sphincter function. The use of three-dimensional imaging is valuable to the physician in the determination of the presence of a muscular defect, the location of the defect and the appropriateness of surgical intervention to resolve the anal dysfunction. PMID- 1878389 TI - Practical considerations of the gastrostomy button. AB - Low-profile gastrostomy replacement devices (LPGRDs), also called gastrostomy buttons, provide patients with a desirable alternative to traditional catheters. Contraindications to LPGRDs include acutely angled gastrostomy tracts, tracts created with a mucosa lining, the need for jejunal feedings or significant decompression, planned retroesophageal dilation and tracts that are longer than the LPGRDs. Gastrostomy and patient considerations lead to a variety of scheduling practices. Management adaptations help maintain LPGRD patency and functioning of the anti-reflux valve and plug. Other adaptations are necessary for patients receiving thickened feedings or medications per gastrostomy, needing intermittent decompression or having high intra-abdominal pressure. Determining the correct LPGRD size and dilating the tract or cauterizing conclude this discussion which is summarized in a checklist following the text. PMID- 1878390 TI - Position statement. Responsibilities of the gastroenterology registered nurse related to conscious sedation. PMID- 1878391 TI - Position statement. Manipulation of endoscopes during endoscopic procedures by gastroenterology nurses and associates. PMID- 1878392 TI - A new approach to esophageal varices: endoscopic variceal ligation. AB - Bleeding from esophageal varices is a devastating complication of portal hypertension and is associated with a high mortality rate. The management goals for this group of patients are to achieve hemostasis in the acute phase, reduce variceal size, reduce the potential of rebleeding and eliminate varices with a follow-up program. For the past two decades, the gold standard of treatment has been endoscopic sclerotherapy but at the expense of many complications, which often cause serious morbidity. Endoscopic variceal ligation was developed as an alternative to endoscopic sclerotherapy. The experience to date shows that the goals of therapy can be achieved with fewer complications than those associated with sclerotherapy. PMID- 1878393 TI - The transition to video: considerations for the GI laboratory manager. AB - During the past few years, endoscopic technology has moved increasingly toward the use of video equipment. As a GI laboratory manager, one is confronted with many tasks in converting the unit practice from fiberoptic equipment to video equipment. This article will examine the steps in that process. PMID- 1878394 TI - Techniques in performing continuous distal esophageal pH monitoring in infants. AB - Clinically significant gastroesophageal reflux in infants can be diagnosed accurately by using sophisticated recording equipment and standardized procedure methods. Consistency in the performance of continuous distal esophageal pH monitoring will provide precise, reliable and accurate results. PMID- 1878395 TI - Blood and blood product administration. PMID- 1878396 TI - Towards a process evaluation model for community-based initiatives aimed at preventing the spread of HIV amongst injecting drug users. AB - An action research model is presented for the evaluation of community-based interventions. The short- and long-term application of this model is illustrated by means of a study of a community drug team which was initiated to prevent the spread of HIV infection amongst substance misusers in south-west London. A client caseload of 155 was monitored over a year-long period and the results used to evaluate the extent to which the CDT had achieved its stated aims and objectives. Other tools used in the evaluation and monitoring were surveys of generic, specialist and general practitioner services, and needs assessment of samples of drug users. The potential of the model is explored, both in terms of its research role and in facilitating service development. The value of action research methodology in assessing HIV/AIDS prevention is stressed. PMID- 1878397 TI - Stressors and rewards of being an AIDS emotional-support volunteer: a scale for use by care-givers for people with AIDS. AB - This study describes scales which can be used to identify the levels of stress and reward associated with being a AIDS emotional-support volunteer. Four categories of stressors were identified. These were 'emotional overload', 'client problems', 'lack of support' and 'lack of training'. The reward categories were 'personal effectiveness', 'emotional support', 'social support' and 'empathy/self knowing'. There were low, but positive correlations between these stressor scales and other measures of psychological morbidity, the 28-item General Health Questionnaire (GHQ) and the Maslach Burnout Inventory (MBI). Levels of stress and reward were positively correlated and, taken together, the scales may be of use as a measure of the degree of involvement of volunteers in the AIDS care-giving process. Although these scales were derived from items provided from AIDS emotional-support volunteers many of the items may also be relevant to other health workers providing care for people with AIDS. PMID- 1878398 TI - Compulsory HIV antibody testing, universal precautions and the perceived risk of HIV: a survey among medical students and consultant staff at a London teaching hospital. AB - Routine screening of patients and health care staff for HIV has not been endorsed by the medical profession. Instead universal precautions have been recommended as being the most effective way of minimizing the occupational risk of HIV infection. Consultant staff and undergraduate medical students at the Royal Free Hospital and School of Medicine, London, were asked about their attitudes towards compulsory HIV antibody testing, their compliance with universal precautions and their perceived risk of HIV infection. A substantial proportion of staff and students supported compulsory HIV antibody testing for patients, health care workers and certain subgroups of the population. Most of the clinical students and about half the consultants failed to comply with universal precautions. Staff and students saw themselves at greater risk of HIV infection in the hospital than in their personal lives. Clearly, these beliefs and practices must be taken into account when introducing a policy of universal precautions. PMID- 1878399 TI - Counselling patients with HIV infection about laboratory tests with predictive values. AB - Laboratory tests, including CD4 counts, p24 antigen, raised levels of B2 microglobulin, neopterin and CMV antibodies, have been established as important predictive markers of disease progression in patients with HIV infection. As HIV antibody testing becomes more accepted in medical practice, counselling about these laboratory predictors of progression can help patients and doctors plan together the patients' care and treatment. Addressing patients' main concerns at each stage of investigation and illness may help them to plan ahead of crises, reduce stress, and enhance communication between patients and health care providers. PMID- 1878400 TI - HIV infection in persons with prior mental retardation. AB - This paper presents five case studies of persons who were mentally retarded prior to infection with human immunodeficiency virus (HIV). Particular emphasis is placed on neuropsychological functioning, and its interaction with management and treatment. The effects of HIV on neurological functioning in such persons has not been previously documented. Although it may be hypothesized that mentally retarded people are at increased risk for developing neurological complications, these preliminary data suggest this is not so and that the development of HIV related encephalopathy is no different in the mentally retarded, manifesting in the AIDS-related complex (ARC) and AIDS stages of illness. Within the context of HIV infection, the cognitive status of the mentally retarded creates unique treatment and management difficulties, and some guidelines are presented. PMID- 1878401 TI - Dimensions, content and validation of the fear of AIDS schedule in health professionals. AB - We examined the structure of the Fear of AIDS Schedule (FAIDSS) in a sample of 134 health care workers. Factor analysis indicated that there were five discrete dimension of fear of AIDS: fears of loss of control, of sex, of HIV infection through blood and illness, of death and medical interventions, and of contact with outsiders. These dimensions had low to moderate intercorrelations. The dimensions of fear of HIV infection through blood or illness, was significantly correlated with desired personal social distance from people with AIDS, and this dimension along with fear of death and medical interventions were correlated with desired public social distance. Fear of infection through blood and illness were predictors of both desired personal social distance and public social distance from people with HIV infection. The data suggest greater discrimination of AIDS fears with greater closeness of interaction with people with HIV disease, and that these dimensions of the FAIDSS are both reliable and valid measures of AIDS fears. PMID- 1878402 TI - Quantitative analysis of burnout and its associated factors in AIDS nursing. AB - A study was conducted to examine burnout and associated factors in the nursing care of AIDS patients in the hospital setting. Oncology nurses served as a comparison group and 64 subjects completed the Maslach Burnout Inventory. Although nurses working in the area of Oncology suffered burnout with greater frequency, nurses working in the area of AIDS showed greater intensity of burnout after adjustment for frequency of burnout. The study identified hospital differences in burnout scores, lending support to the environmental model of burnout proposed by Maslach. Male nurses were as likely to suffer burnout as female nurses. Having previously worked in other stressful areas did not influence burnout scores. On the other hand nurses who had worked in a particular unit for a greater length of time were more likely to suffer burnout, and age significantly influenced burnout inversely. PMID- 1878403 TI - The impact of HIV upon injecting drug users: a longitudinal study. AB - This paper provides quantitative and qualitative material relating to concern about HIV infection and AIDS, HIV status and patterns of drug use, and sexual behaviour amongst 14 injecting drug users. It is part of a longitudinal study involving interviews with 115 regular illicit drug users conducted between December 1987 and June 1988, of whom 21 were current injectors. Follow-up interviews with 14 of these injectors were conducted between September 1989 and April 1990. Whilst there are some encouraging signs of behaviour change in relation to needle-sharing, sexual behaviour change was less apparent. It is concluded that there is still a long way to go in terms of encouraging, facilitating and supporting continued safer practices. PMID- 1878404 TI - The development of a community-based HIV/AIDS counselling service in a rural area in Uganda. AB - This paper describes the evolution of a counselling service in the context of an HIV/AIDS research programme in rural Uganda. The background to AIDS counselling both in Europe/America and in Africa is outlined first, and the cultural context of the programme explained. The evolution of the counselling procedure is then described and village case studies are used to illustrate the development and the difficulties that have been faced in finding an appropriate counselling model. It is noted that the Euro-American model of person-to-person counselling needs to be adapted to the rural African setting, by placing the emphasis on support for the family. It is emphasized that the approach to counselling needs to remain flexible and sensitive to the sociocultural context in which it is developed. PMID- 1878405 TI - World Health Organization Global AIDS Statistics. PMID- 1878406 TI - Sequence-selective DNA recognition by synthetic ligands. PMID- 1878407 TI - (N-succinimidyl 4-pentynoate)hexacarbonyldicobalt: a transition-metal carbonyl complex having similar uses to the Bolton-Hunter reagent. AB - The synthesis of the transition-metal carbonyl complex (N-succinimidyl 4 pentynoate)hexacarbonyldicobalt [[(C4H4O2N)O(CO)CH2CH2C identical to CH]Co2(CO)6] is described. This cobalt carbonyl complex is structurally similar to the Bolton Hunter conjugation reagent and has been successfully employed as a nonradioactive tracer for labeling the drug carbamazepine. The metal carbonyl tracer can be detected at extremely low concentrations (ca. 1 pmol) by FT-IR spectroscopy in the v(CO) region (2150-1800 cm-1). The cobalt carbonyl labeled carbamazepine retains good recognition for anti-carbamazepine antibodies. This novel labeling procedure, which can be broadly termed carbonylmetalloimmunoassay (CMIA), has considerable potential for assaying a wide range of biological materials. PMID- 1878408 TI - Production of macrophage-derived cytotoxic factor by N-[3 [(carbamoylmethyl)thio]propionylated] neoglycoproteins. AB - 6-Phosphomannosylated bovine serum albumin (Man6P-BSA), a neoglycoprotein endocytosed by macrophages, bearing either 3-(2-pyridyldithio)propionyl or 3 [(carbamoylmethyl)thio]propionyl residues coming from alkylation of thiol residues by iodoacetamide were prepared and tested for their immunomodulator properties. The supernatants of mouse peritoneal macrophages incubated with Man6P BSA bearing 3-[(carbamoylmethyl)thio]propionyl groups, and by a lesser extent 3 (2-pyridyldithio)propionyl groups, were cytotoxic to L929 cells, suggesting the presence of a tumor necrosis factor like compound. This macrophage-activation process is linked to the capacity of Man6P-BSA to be endocytosed via membrane lectins of macrophages, because the supernatants of macrophages incubated with unglycosylated conjugates were not cytotoxic. The cytotoxic activity induced by 3 [(carbamoylmethyl)thio]propionyl groups bound onto Man6P-BSA was similar to that induced by Man6P-BSA bearing muramyl dipeptide, indicating that endocytosed neoglycoproteins bearing 3-[(carbamoylmethyl)thio]propionyl residues are potent macrophage activators. PMID- 1878409 TI - Immunoadsorbents with synthetic oligosaccharide hapten representing blood group A substances. AB - Immunoadsorbents with a synthetic oligosaccharide hapten representing human blood group A specific substances are prepared. The synthetic hapten, known as A trisaccharide, which carries a space arm, is chemically attached to various solid supports, either directly through a suitable functional group at the end of the spacer arm or indirectly via a protein conjugated to the hapten. The preparation involves simple and mild procedures for the activation and/or derivatization of the supports. The latter includes naturally occurring polyhydroxy materials such as agarose, cellulose, or cellulose derivatives, and other particulate materials such as inorganic diatomites and a synthetic organic copolymer. The methods used for the coupling concern specifically the preparation of controlled-capacity and high-efficiency immunoadsorbents, with limited incorporations, which may be prepared easily and used for the selective removal, or affinity chromatographic separation, of specific antibodies from plasma environment or blood. It has been found that while hapten incorporation to the support may be varied rather easily, the physical nature of the support as well as the form of the hapten is important in determining the efficiency of an immunoadsorbent. PMID- 1878410 TI - Fluorine-18 labeling of monoclonal antibodies and fragments with preservation of immunoreactivity. AB - A new method is reported for labeling proteins with the positron-emitting nuclide 18F. Initially, 4-[18F]-fluorobenzylamine was prepared in two steps from aqueous [18F]fluoride in high yield. The 18F acylation agent was formed by reaction of this product with disuccinimidyl suberate. Overall yields for the 4 [18F]fluorobenzylamine succinimidyl ester ([18F]SFBS), decay corrected to the end of cyclotron bombardment, were about 30% in a synthesis time of 60 min. After a 15-min reaction, 30-45% (decay corrected) of the [18F]SFBS could be coupled to intact antibodies and their F(ab')2 and Fab fragments. Coupling yields were dependent on protein concentration but not reaction time. HPLC purification of [18F]SFBS was necessary to obtain optimal coupling efficiency and immunoreactivity. The immunoreactivities of 18F-labeled F(ab')2 and Fab fragments of an antimyosin antibody were 89 +/- 5% and 75 +/- 9%, respectively. Biodistribution studies in normal mice demonstrated similar in vivo behavior of 18F-labeled antibody fragments and those labeled with 125I by using N succinimidyl 3-[125I]iodobenzoate. These results indicate that this method may be useful for labeling monoclonal antibodies and other proteins and peptides with 18F. PMID- 1878411 TI - N-succinimidyl 5-(trialkylstannyl)-3-pyridinecarboxylates: a new class of reagents for protein radioiodination. AB - N-Succinimidyl 5-(trialkylstannyl)-3-pyridinecarboxylates (alkyl = Me, Bu) have been prepared and used as a precursor to label N-succinimidyl 5-[131I]iodo-3 pyridinecarboxylate (SIPC). SIPC was obtained in greater than 80% yield from either the methyl or butyl precursor with N-chlorosuccinimide and heating at 60 65 degrees C. Significantly lower yields were observed with tert-butyl hydroperoxide. After a 30-min incubation with [131I]SIPC at pH 8.5, goat IgG, an intact monoclonal antibody (MAb), and a MAb F(ab')2 fragment were labeled in 60 65% yield. Specific binding of the MAb and MAb fragment after SIPC labeling was identical with that observed with N-succinimidyl 3-iodobenzoate and higher than that reported previously for these MAbs after labeling by using the Iodogen method. When 5-[131I]iodonicotinic acid was injected into normal mice, thyroid uptake was less than 0.2% of the injected dose, reflecting the inertness of this compound to deiodination. Paired-label biodistribution studies indicate that for both the MAb and the F(ab')2 labeled by using SIPC, accumulation of activity in the thyroid and other tissues is comparable to that observed when these proteins were labeled by using N-succinimidyl 3-iodobenzoate. The results of this study suggest that SIPC may be a reagent for labeling MAbs with halogen nuclides. PMID- 1878412 TI - Models of membrane resonance in pigeon semicircular canal type II hair cells. AB - Pigeon vestibular semicircular canal type II hair cells often exhibit voltage oscillations following current steps that depolarize the cell membrane from its resting potential. Currents active around the resting membrane potential and most likely responsible for the observed resonant behavior are the Ca(++)-insensitive, inactivating potassium conductance IA (A-current) and delayed rectifier potassium conductance IK. Several equivalent circuits are considered as representative of the hair cell membrane behavior, sufficient to explain and quantitatively fit the observed voltage oscillations. In addition to the membrane capacitance and frequency-independent parallel conductance, a third parallel element whose admittance function is of second order is necessary to describe and accurately predict all of the experimentally obtained current and voltage responses. Even though most voltage oscillations could be fitted by an equivalent circuit in which the second order admittance term is overdamped (i.e., represents a type of current with two time constants, one of activation and the other of inactivation), the sharpest quality resonance obtained with small current steps (around 20 pA) from the resting potential could be satisfactorily fit only by an underdamped term. PMID- 1878413 TI - The role of structural symmetry in linearizing ocular reflexes. AB - This work presents a simulation study using an anatomically relevant model of the vestibulo-ocular reflex (VOR). The aim is to explore the functional properties of a bilateral structure in the premotor circuits of the oculomotor system. The major conclusions using sinusoidal inputs are: A bilateral structure in a sensory motor system improves its linear range beyond expected central limits, if provided with symmetric interconnections. Given a bilateral (push-pull) sensory arrangement, non-linear sensor characteristics are actually advantageous. The greatest improvement in linear range of the reflex (here VOR) relies on intact sensors on both sides. In the case of a single sensor (unilateral head velocity input), or unmatched bilateral sensors, this study predicts a decrease in the linear range and the appearance of a variable bias. These implications are compatible with available data and can be tested in a clinical environment. PMID- 1878414 TI - Probability density function of successive intervals of a nonhomogeneous Poisson process under low-frequency conditions. AB - The probability density function (pdf) of successive intervals of a truncated, nonhomogeneous Poisson process was examined under both low- and high-frequency conditions. In general, if the instantaneous rate contains a single frequency component, then the phase of this component is not represented in the interval pdf. However, if the instantaneous rate contains harmonically related components, with fundamental frequency of the same order as, or less than, the mean rate, then the phases of these components do appear in the interval pdf. Correction formulae for estimating synchronization indices under low-frequency conditions are derived. PMID- 1878415 TI - Simulation of local evolutionary dynamics of small populations. AB - A simple stochastic model assuming continuous traits, normally distributed modifications, selection for fertility and multiplicative fitness was used to simulate phenotypic evolution by "reproducing individuals" in a given fitness landscape. Of particular interest was how small populations cross saddles separating distinct adaptive peaks. The simulated evolution exhibits a strong dualism: at the same level of reproductive errors, sexual reproduction provides significantly better local adaptation and asexual reproduction provides significantly better adaptive dynamics. PMID- 1878416 TI - On the rate of convergence in topology preserving neural networks. AB - A formal analysis of the neighborhood interaction function selection in the topology preserving unsupervised neural network is presented in this paper. The definition of the neighborhood interaction function is motivated by anatomical evidence as opposed to what is currently used, which is a uniform neighborhood interaction set. By selecting a neighborhood interaction function with a neighborhood amplitude of interaction which is decreasing in spatial domain the topological order is always enforced and the rate of self-organization to final equilibrium state is improved. Several simulations are carried out to show the improvement in rate between using a neighborhood interaction function vs. using a neighborhood interaction set. An error measure functional is further defined to compare the two approaches quantitatively. PMID- 1878417 TI - Controlling the dynamics of a two-joined arm by central patterning and reflex like processing. A two-stage hybrid model. AB - It is demonstrated, that a two-joined arm performing goal directed movements is controllable (a) by two central pattern generators (CPG) representing sampled data control, each referring to one joint, initiated for exactly one period, and producing the angular movement width about this joint, and (b) by reflex-like processes operating continuously with respect to time. The latter eliminate the effects of dynamic coupling, gravity, inertia, and mechanical impedance on the movement by 'proprioceptive feedforward' of position, velocity and acceleration signals, thus enabling the CPGs to handle the arm segments as if they were independent and free from forces. Higher ordered centers (with respect to the CPGs) therefore only need to control the kinematics, not dynamics, of the arm. PMID- 1878418 TI - On the dynamic organization of memory. A mathematical model of associative free recall. AB - The interaction of memory structures and retrieval dynamics is discussed. A mathematical model for associative free recall is presented to support the view that the organization of simple processing units plays an important role in the retrieval of memory traces. Computer simulations show that "flexibility" and "fidelity" of the dynamics strongly depend on the network structure, the amplification and decay parameters, and the noise term. PMID- 1878419 TI - Treatment of early stage-B chronic lymphocytic leukemia with alpha-2b interferon after chlorambucil reduction of the tumoral mass. AB - Eleven patients with early CLL (two in Rai's stage 0, seven in stage I, and two in stage II) received aIFN (3 MU subcutaneously three times a week for a median of 8 months; range, 4-12) after their tumor mass had been reduced with intermittent chlorambucil. Following chlorambucil/aIFN administration, a significant reduction in blood lymphocyte counts (from 25.1 +/- 12.0 x 10(9)/l to 6.3 +/- 5.32 x 10(9)/l; p less than 0.001) and in CD 19-positive cells (from 21.0 +/- 12.0 x 10(9)/l to 3.8 +/- 2.3 x 10(9)/l; p less than 0.001) was observed. Three of seven patients with stage-I and one of two with stage-II disease moved to stage 0, and a complete response (CR) was observed in two patients with stage I at diagnosis. Overall, there were eight patients who, after treatment, had either a CR (2 cases) or stage-0 disease (6 cases), which compares favorably with two patients with stage-0 disease before entering the study (p = 0.015). In five patients (including the two who achieved a CR) aIFN further improved the disease status achieved with chlorambucil. PMID- 1878420 TI - The influence of blood donation on iron stores assessed by serum ferritin and hemoglobin in a population survey of 1359 Danish women. AB - The general impact of blood donation on iron status was studied in a population survey comprising 1359 nonpregnant Danish women in age cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550 postmenopausal; 180 (13%) were blood donors. Iron stores were assessed by serum (S)-ferritin and hemoglobin (Hb). Hb levels were not significantly different in donors: mean 137 +/- 10 (SD) g/l (8.5 +/- 0.6 mmol/l) compared with nondonors, 139 +/- 11 g/l (8.6 +/- 0.7 mmol/l). Values less than 121 g/l (7.5 mmol/l) were observed in 3.3% of donors vs 3.8% of nondonors. Correlations between S-ferritin and Hb were without practical relevance: rs = 0.29, p less than 0.0001 in donors vs rs = 0.22, p less than 0.0001 in nondonors. Blood donation had a profound influence on iron status, especially in the premenopausal women population. Donors had lower S-ferritin than nondonors in all age-groups and in pre- and postmenopausal groups (p less than 0.001 in all groups). Premenopausal donors had a median S-ferritin of 31 micrograms/l vs 39 micrograms/l in nondonors, postmenopausal donors of 47 micrograms/l vs 72 micrograms/l in nondonors. S-ferritin values less than 15 micrograms/l (i.e., depleted iron stores) were observed in 31.7% of premenopausal donors vs 15.2% of nondonors, and in 7.0% of postmenopausal donors vs 2.9% of nondonors. Iron deficiency anemia (i.e., S-ferritin less than 15 micrograms/l and Hb less than 121 g/l) was seen in 2.8% of donors vs 1.5% of nondonors. Donors using oral contraceptives had higher S-ferritin, median 33 micrograms/l compared with nonusers, 22 micrograms/l, and a lower frequency of depleted iron stores, 29% vs 39%. Ideally, the frequency of phlebotomy should be adjusted according to S-ferritin as well as Hb levels. If Hb is used as single criterion for donation, only donors with predonation values greater than or equal to 124-125 g/l should be allowed to undergo phlebotomy. PMID- 1878421 TI - Hepatic and splenic abscesses--a common complication of intensive chemotherapy of acute myeloid leukemia (AML). A prospective study. AB - In order to determine the frequency of hepatosplenic abscesses in AML patients during chemotherapy and to evaluate the clinical and laboratory characteristics of this complication we performed a prospective study over a 28-month period. Fifty-five consecutive patients with de novo AML or relapse who received intensive chemotherapy underwent regular ultrasound examinations. In 16 patients (29.1%) hepatic and/or splenic abscesses were detected sonographically. Histopathological evidence for abscess formation was obtained in five of these 16 patients. In three patients granulation tissue and in one patient necrotizing granulomas were found. Causative micro-organisms were proven in only three patients: Candida hyphae were demonstrated in one patient, gram-positive cocci in another. Bacteria and fungi were seen in the tissue specimen of the third patient. Patients with hepatosplenic abscesses had significantly prolonged fever after neutrophil recovery but did not differ from patients without abscesses in any other laboratory or clinical features. Due to the absence of specific alerting clinical and laboratory signs and symptoms of hepatosplenic abscesses, routine ultrasound examination is required for detection of this complication. The presence of hepatic and/or splenic abscesses does not necessarily worsen the prognosis, but it may influence the decision on further chemotherapy and antimicrobial treatment. PMID- 1878422 TI - A Czechoslovakian teenager with Hb E-beta zero-thalassemia [IVS-I-1 (G----A)] complicated by the presence of an alpha-globin gene triplication. AB - We have examined the molecular basis of three inherited hemoglobin (Hb) disorders present in a Czechoslovakian girl with a severe, transfusion-dependent, hemolytic anemia. She is heterozygous for Hb E (on a genetic background specific for Czechoslovakian families), heterozygous for the beta zero-thalassemia (thal) allele IVS-I-1 (G----A), and heterozygous for an alpha-globin gene triplication. The combination of these three undesirable traits results in a severe chain imbalance that is the basis of the serious hemolytic disorder observed in this teenager. PMID- 1878423 TI - Effects of suramin on phagocytes in vitro. AB - In the therapeutically important range (100-200 micrograms/ml), suramin was found to increase the phagocytic activity of human monocytes (measured by the uptake of Saccharomyces cerevisiae and sensitized sheep red blood cells) in vitro. Suramin itself was a chemotactic signal for monocytes and increased the chemiluminescence of neutrophil granulocytes. Suramin seems to act via the ATP-binding P2 receptors of human phagocytes. PMID- 1878424 TI - Studies on the role of recombinant human erythropoietin in the growth regulation of human nonhematopoietic tumor cells in vitro. AB - Recombinant human (rh) erythropoietin (EPO) is attracting increasing interest as an agent for treating cancer-related anemia. Thus, we have tested the effects of rhEPO on the clonal growth of 22 different cell lines derived from a wide range of human solid tumors (head and neck 3, lung 2, breast 2, stomach 1, colorectal 3, hepatocellular 1, pancreas 1, ovary 1, choriocarcinoma 1, osteogenic sarcoma 1, glioblastoma 2, neuroblastoma 1, prostate 1, renal 2) in vitro. RhEPO (dose range 0.01-100 U/ml) caused no significant and reproducible stimulation of clonal growth as measured by a capillary modification of the human tumor cloning assay in agar in any of the cell lines tested. In particular, there was no sensitivity for rhEPO of those cell lines which were shown to be responsive to interleukin-3 and GM-CSF. On the other hand, there were no growth inhibitory effects of rhEPO on the cell lines of this study. Finally, neutralizing anti-human EPO antibody had no effect on the clonal growth of two kidney carcinoma cell lines, making autocrine growth regulation by hEPO in these lines unlikely. PMID- 1878425 TI - Immune hemolytic anemia and renal failure associated with rifampicin-dependent antibodies with anti-I specificity. AB - A 50-year-old woman with primary biliary cirrhosis developed immune hemolytic anemia and renal failure while receiving rifampicin for the treatment of refractory pruritus. Serological studies revealed the presence of rifampicin dependent antibodies of the IgM class that, when tested against a wide panel of erythrocytes, had anti-I specificity. Subsequently, rifampicin was withdrawn and prednisone treatment instituted, this resulting in a rapid resolution of the hemolysis, whereas hemodialysis was required for recovery of the renal function. A role is suggested for the anti-I specificity of the antibodies in the development of renal failure associated with rifampicin therapy. PMID- 1878426 TI - Synchronization of the circannual reproductive rhythm of the ewe by discrete photoperiodic signals. AB - Although many species display endogenous circannual rhythms of biological activity that are synchronized by day length, the specific photoperiodic requirements for synchronizing such rhythms are not established for any species. We tested the hypothesis that the circannual reproductive rhythm of sheep can be synchronized by exposure to just one or two discrete blocks of photoperiodic information each year. Ewes were pinealectomized to prevent their ability to transduce photoperiodic information into altered reproductive neuroendocrine activity. During the 53/4 yr following pinealectomy, specific photoperiodic signals were restored for discrete periods of time via replacement of 24-h patterns of melatonin, the pineal hormone that transmits photic information to the reproductive neuroendocrine axis. The ewes were kept in a 12-mo photoycycle that alternated between short (8L:16D) and long (16L:8D) days every 6 mo and that was 6 mo out of phase with the geophysical year. Pineal-intact control ewes exhibited synchronous annual reproductive cycles. Noninfused pinealectomized control ewes did not exhibit synchronous cycles. Pinealectomized ewes infused with alternating 70-day blocks of short- and long-day patterns of melatonin every 6 mo for the first 21/2 yr of the experiment exhibited synchronous annual reproductive cycles that were 6 mo out of phase with those of ewes maintained outdoors. This synchrony persisted when the frequency of the melatonin treatment was reduced to just one 70-day block of a long-day pattern of melatonin each 365 days. Cycle period was 368 +/- 3 days; standard deviation of the date of onset of reproductive induction averaged only 3 days. Our study provides the first direct evidence that a single block of photoperiodic information a year can synchronize a circannual rhythm. PMID- 1878427 TI - Direct pituitary effects of estradiol and progesterone on luteinizing hormone release, stores, and subunit messenger ribonucleic acids. AB - To determine the direct, chronic actions of progesterone (P4) and estrogen (estradiol, E2) on anterior pituitary synthesis and release of LH, 24 western range ewes underwent hypothalamic-pituitary disconnection (HPD) and ovariectomy (OVX) during the breeding season and were pulsed with exogenous GnRH with or without steroid replacement. Sequential blood samples were collected before infusion of GnRH and on Days 7 and 14 of GnRH infusion. Silastic capsules of P4 and/or E2 were implanted s.c. on Day 7 and remained in place throughout the experiment. Control ewes received only GnRH infusion. Blood sampling was centered around three exogenous GnRH pulses. After the final blood sampling, pituitaries were collected and stored at -70 degrees C. Concentrations of LH in serum and pituitaries were determined by RIA. Relative concentrations of LH subunit mRNAs were determined by Fast Blot analysis. Simultaneous implantation of P4 and E2 lowered LH pulse amplitude 70% and mean serum levels 30% compared with controls. Neither steroid alone affected LH release. E2 alone or in combination with P4 lowered LH-beta subunit mRNA concentrations 40% compared with controls while alpha-subunit levels were unchanged. Only E2 alone altered the pituitary content of LH, causing a 60% decrease. We conclude that the combination of P4 and E2 is necessary for inhibition of GnRH-stimulated LH secretion. E2 inhibits GnRH stimulated LH-beta subunit mRNA concentrations but does not affect alpha-subunit mRNA concentrations. The control of pituitary LH content by P4 and E2 is the result of changes in both LH-beta subunit mRNA concentrations and LH secretion. PMID- 1878428 TI - Insulin-like growth factors in sheep uterine fluids: concentrations and relationship to ovine trophoblast protein-1 production during early pregnancy. AB - Uterine luminal fluids (ULFs) from Days 10, 12, 14, and 16 cyclic (C) and pregnant (Px) ewes were analyzed for presence of insulin-like growth factors (IGF I, IGF-II) and other mitogenic factor(s). IGF content and non-IGF mitogenic activity were measured by IGF RIAs after removal of IGF binding proteins and by stimulatory effects on DNA synthesis of density arrested AKR-2B cells, respectively. ULF IGF-I content was not different between days, but differences in IGF-I between C and Px groups at Day 16 (C greater than Px) were found (p less than 0.05). ULF IGF-II content was not different between C and Px ewes; however, differences among days (p less than 0.01) were apparent. In both C and Px ewes, Day 14 ULF had highest IGF-II content (C: 4.60 +/- 0.98 ng/ml, Px: 5.39 +/- 1.38 ng/ml). In Day 12 and Day 14 (C and Px) ULF, IGF-II concentration was about 10 fold greater than that of IGF-I. AKR-2B mitogenic activity in ULF differed among days (p less than 0.01), but not between C and Px ewes. Highest activity was observed for Day 14 and Px ULF, whereas lowest activity was for Day 10 C and Day 16 Px ULF. Sephadex G-200 gel-filtration chromatography of ULF from Day 14 Px ewes demonstrated mitogenic activity in the column void volume fractions and in the 30-kDa size range of eluted proteins. Day 13 conceptuses were cultured in serum-free medium to define the effect of exogenous IGFs on ovine trophoblast protein-1 (oTP-1) secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878429 TI - Human chorionic gonadotropin treatment prevents depressed 17 alpha hydroxylase/C17-20 lyase activities and serum testosterone concentrations in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats. AB - It is known that administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes decreased serum testosterone concentrations in the rat. Previous studies in this laboratory have shown that in rats TCDD exposure results in decreased 17 alpha-hydroxylase and C17-20 lyase activities. The decreases in these activities paralleled decreases in testicular microsomal heme and cytochrome P450 contents. As reported herein, neither testicular mitochondrial cytochrome P450 content nor the activity of cholesterol side-chain cleavage was altered in rats exposed to TCDD. Since the production of testosterone in the testis is dependent on LH, it is important to determine the early effects of TCDD on serum LH concentrations in the rat. Male Sprague-Dawley rats were given a single, oral dose of TCDD (50 micrograms/kg). Serum LH concentrations were determined by RIA on Days 1, 2, 3, 5, and 7 following TCDD treatment. Rat serum LH concentrations were decreased to 60% of controls as early as Day 1 and continued to be depressed on Days 2 and 3 at 53% and 59% of control values, respectively. Rat serum LH returned to control values by Day 5 in spite of continued depression of serum testosterone concentrations. The early depression in serum LH levels caused by TCDD may be related to the subsequent androgenic deficiency in the rat. Treatment of rats with hCG was found to be able to prevent the depression of the activities of testicular microsomal 17 alpha-hydroxylase and C17-20 lyase and serum testosterone concentrations caused by TCDD. These data indicate that TCDD decreases serum testosterone by decreasing P450(17 alpha) and C17-20 but not P450sec activities and that hCG treatment prevents the TCDD-induced decrease. PMID- 1878430 TI - Effects of neonatal exposure to diethylstilbestrol on early mouse embryo development in vivo and in vitro. AB - Eight-week-old female mice of the NMRI strain that had been treated neonatally with diethylstilbestrol (DES, 5 micrograms/day for five days) or not (controls) were treated with gonadotropins to induce ovulation and then were artificially inseminated. Ova or young embryos were recovered from the oviducts on the morning after insemination and on Days 2, 3, and 4. In other experiments, ova were obtained from inseminated females on the morning after ovulation and cultured in vitro. In DES-treated females, a few zygotes developed to the 4-cell stage, but no more advanced stages were seen. Under in vitro conditions, zygotes from DES treated females developed into blastocysts and to the implantation stage, but the incidence of these stages was lower than with zygotes from controls. Our results point to an abnormal oviductal function in DES-treated females that is not compatible with early embryo survival, even though an additional zygote factor contributing to degeneration of early cleavage stages cannot be excluded. PMID- 1878431 TI - Fertility of transgenic female mice expressing bovine growth hormone or human growth hormone variant genes. AB - Although growth hormone (GH) exerts various direct and indirect stimulatory effects on gonadal development and function, excessive levels of GH in acromegalic patients and in transgenic animals are often associated with reproductive disorders. We have examined reproductive performance of transgenic female mice expressing the following hybrid genes: mouse metallothionein-1 (MT)/human placental GH variant (hGH.V), MT/bovine GH(bGH), and phosphoenolpyruvate carboxykinase (PEPCK)/bGH. This allowed us to evaluate the effects of chronic GH excess in three animal models and to obtain some information on the significance of the lactogenic activity of the foreign GH (hGH.V vs. bGH) and on the developmental stage of transgene expression (MT vs. PEPCK). Transgenic animals from each line had elevated plasma insulin-like growth factor-I levels and greatly increased adult body weight. Plasma bGH levels were significantly higher in PEPCK/bGH than in MT/bGH transgenic mice. Approximately 20% of transgenic MT/hGH.V and MT/bGH females and over 60% of transgenic PEPCK/bGH females were infertile. Transgenic females that did reproduce ovulated either a normal or increased number of eggs but exhibited a variety of reproductive disorders including increased interval between pairing with a male and conception, increased interval between litters, reduced number of litters, reduced fetal growth, increased pre- and postnatal mortality, and alterations in sex ratio. Among adult offspring of these females, the proportion of transgenic animals was significantly less than the expected 50%. While some characteristics (e.g., fetal crown-rump length and weight on Day 14 of pregnancy) were affected to a comparable extent in transgenic females from all three lines, MT/hGH.V and PEPCK/bGH females were, in general, more severely affected than the MT/bGH animals. Sterility of PEPCK/bGH females appeared to be due to luteal failure since treatment with progesterone led to pregnancy. Greatly increased intervals between successive litters appeared to be due to failure to mate during postpartum estrus and to sterile matings during this period. Reduced fetal size and weight may have been due to chronic glucocorticoid excess because comparable changes could be induced in normal females by injections of dexamethasone during pregnancy, and plasma corticosterone levels were previously shown to be elevated in transgenic mice from each of these lines. Comparison of these results with data obtained from matings of normal female mice to transgenic males from the same lines suggests that reduced fetal growth is due primarily to maternal genotype, while reduced "transmission" of the hybrid genes is not, and presumably reflects increased mortality of transgenic progeny at various stages of development.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1878432 TI - Testosterone inhibits gonadotropin-releasing hormone pulse frequency in the male sheep. AB - The objective was to determine the effect of chronic testosterone (T) treatment on GnRH and LH secretion in wethers. Rams were either castrated only or castrated and immediately treated with Silastic implants containing T. Several weeks later, a device for collecting hypophyseal-portal blood was surgically implanted. Six to seven days later, blood samples were collected simultaneously and continuously from the portal vessels and jugular vein of pairs of conscious animals. Samples were divided at 10-min intervals for 6-12 h. One hour before the end of collection, all animals received i.v. injections of 250 ng of GnRH. In samples collected simultaneously from 6 pairs of animals, T reduced the frequency of both GnRH pulses (1.8 +/- 0.2 vs. 0.9 +/- 0.3/h, p less than 0.03) and LH pulses (1.6 +/- 0.1 vs. 0.8 +/- 0.3/h, p less than 0.03). T did not alter amplitude of either GnRH or LH pulses. Testosterone reduced mean GnRH (9.7 +/- 0.6 vs. 7.9 +/- 0.5 pg/ml, p less than 0.05), whereas mean LH was not significantly reduced (9.6 +/- 1.4 vs. 6.1 +/- 1.8 ng/ml, p = 0.16). These results support the hypothesis that T reduces GnRH pulse frequency. PMID- 1878433 TI - Localization of sulfated glycoprotein-2 (clusterin) on spermatozoa and in the reproductive tract of the male rat. AB - Sulfated glycoprotein-2 (SGP-2) is one of the major proteins secreted by rat Sertoli cells and epididymal cells in culture. The disulfide-linked dimeric protein secreted by Sertoli cells and found in seminiferous tubule fluid is composed of monomers of Mr 47 000 and 34 000 whereas the epididymal protein exhibits monomers of Mr 40 000 and 29 000. When both forms were chemically or enzymatically deglycosylated, they yielded proteins of similar molecular weight. No modification of the higher molecular weight testicular form by epididymal cells or fluids could be detected in incubation media. SGP-2 mRNA was localized in epididymal epithelium by in situ hybridization. Northern blot analysis indicated the testicular and epididymal mRNAs were of similar size. These findings suggest that the two forms of the protein occur because of tissue specific post-translational modifications. The detergent-extracted protein from washed testicular spermatozoa is of the higher molecular weight form while epididymal sperm carry the lower molecular weight form. Immunohistochemical evidence suggests that the testicular form is removed prior to the initial segment of the epididymis and the epididymal form is applied in the proximal caput epididymidis. SGP-2 was immunolocalized to the sperm membrane at the ultrastructural level and was distinctly different from the immunolocalization of outer dense fiber proteins and fibrous sheath proteins. PMID- 1878434 TI - Estrous cycle-related changes in mast cell numbers in several ovarian compartments in the rat. AB - The absolute number of mast cells in several ovarian compartments was studied during the estrous cycle of the rat. The number of mast cells significantly increased on proestrus (either in the morning or in the evening) in the ovarian medulla and cortex, whereas no significant changes were found in the ovarian bursa. During proestrus, abundant mast cells were present in the bursal cavity along with eosinophil and mononuclear leucocytes. Mast cells in the different ovarian compartments corresponded to mature mast cells, and degranulated or immature cells were only rarely found. These results seem to indicate that migration from an extraovarian source could be the mechanism underlying cyclic changes in ovarian mast cells. PMID- 1878435 TI - Regulation of placental low-density lipoprotein uptake in baboons by estrogen: dose-dependent effects of the anti-estrogen ethamoxytriphetol (MER-25). AB - In the present study, increasing amounts of the anti-estrogen 1-(p-2 diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenoletha nol (MER-25) were administered to pregnant baboons (Papio anubis) to block the action of endogenous estrogen and to determine effect on placental low-density lipoprotein (LDL) uptake. Pregnant baboons were untreated (n = 8) or received MER-25 orally at a dosage of 25 (n = 10), 50 (n = 8), or 75 (n = 4) mg/kg BW daily on Days 140-170 of gestation (term = 184 days). Placentas were removed on Day 170 of gestation and villous tissue was dispersed with 0.1% collagenase. Placental cells (10(6] were incubated in Medium 199 for 12 h at 37 degrees C with increasing amounts of 125I-LDL, with or without a 100-fold excess of unlabeled baboon LDL. Mean (+/- SEM) placental uptake (ng/micrograms cell protein) of 125I-LDL was 55% (6.4 +/- 1.0), 75% (3.6 +/- 0.7), and 81% (2.7 +/- 0.2) lower (p less than 0.001) in baboons that received MER-25 in doses of 25, 50, and 75 mg/kg BW, respectively, than in untreated baboons (14.2 +/- 1.3 ng/micrograms cell protein). Maximal effect occurred with 50 mg MER-25, because LDL uptake was not further decreased with greater levels of MER-25. Dissociation constants for placental LDL uptake, as determined by Scatchard analysis, were unaltered by anti-estrogen treatment. The amount of 125I-LDL degradation by placental cells of untreated and MER-25 treated baboons was proportional to LDL uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878436 TI - Immunological and molecular characterization of plasminogen activator inhibitors 1 and 2 in baboon (Papio anubis) placental tissues. AB - Two major plasminogen activator inhibitors (PAI-1 and PAI-2) increase in the peripheral circulation during pregnancy in humans. PAI-1 is of vascular endothelial origin whereas PAI-2 is produced primarily by human placental tissues. This study was undertaken to determine a) if PAI-1 and PAI-2 are also present in the baboon and b) their association with pregnancy. Citrated plasma was obtained from pregnant baboons sequentially at 15 +/- 3-day intervals between Days 30 and 140 of pregnancy. PAI activity increased significantly (p less than 0.05) at Day 120 (15.3 IU/ml) and 140 (21.8 IU/ml) of gestation and returned to baseline (2.6 IU/ml) 48 h post cesarean section. Placental tissues obtained at cesarean section during the third trimester were either placed in explant culture, fixed for immunocytochemistry, or frozen for RNA extraction. Western blot analysis of tissue culture media (TCM) indicated that the polyclonal antibody to PAI-1 reacted with a major band (Mr 47 000) in TCM from placental tissues while the PAI-2 antibody reacted primarily with a doublet (Mr 67 000 and 69 000) in these same media. PAI-1 was immunocytochemically localized primarily in the chorioamniotic tissue (CAM-D) and PAI-2 was found predominantly in placental villi. Slot blot hybridization with cDNAs to PAI-1 and PAI-2 indicated that the mRNA for PAI-2 was found primarily in placental villi, whereas the mRNA for PAI-1 was present in all three tissue compartments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878437 TI - Regulation of uterine progesterone receptors by the nonsteroidal anti-androgen hydroxyflutamide. AB - We have recently reported that the anti-androgen hydroxyflutamide causes delayed implantation and exhibits antideciduogenic activity in the rat. The present experiments were conducted to examine whether hydroxyflutamide binds to the uterine progesterone receptors and/or alters the progesterone binding sites in the uterus. Cytosol and nuclear fractions from decidualized rat uterus were incubated with [3H]-R5020 without or with increasing concentrations of radioinert R5020, RU486, dihydrotestosterone, or hydroxyflutamide. From the log-dose inhibition curves, the relative binding affinity of both hydroxyflutamide and dihydrotestosterone was less than 0.1% and 2%, compared with R5020 (100%) for displacing [3H]-R5020 bound to uterine cytosol and nuclear fractions, respectively. Injection of estradiol-17 beta (1 microgram/rat) to ovariectomized prepubertal rats induced a 1.85-fold increase in uterine weight by 24 h. Hydroxyflutamide at 2.5 or 5.0 mg did not significantly alter the estrogen induced increase in uterine weight. Compared to vehicle alone, estrogen induced an approximately 5-fold increase in uterine cytosolic progesterone binding sites. Hydroxyflutamide at both 2.5- and 5.0-mg doses significantly attenuated the estrogen-induced elevation in uterine progesterone binding sites. These studies demonstrate that hydroxyflutamide does not bind with high affinity to progesterone receptors, but suppresses the estrogen-induced elevation in progesterone receptor levels in the uterus. PMID- 1878438 TI - The timing of neuroendocrine sexual maturity in the male lamb by photoperiod. AB - In spring-born female lambs, the long days of summer, followed by their gradual decrease, provide the seasonal cue necessary to time puberty to early autumn (approximately 30 wk of age). Male lambs begin spermatogenesis during mid-summer, some 20 wk before puberty occurs in females. Unlike young female lambs, male lambs attain puberty at the same age under a variety of photoperiodic manipulations, raising the possibility that sexual maturation in males is not affected by photoperiod. We have reinvestigated the role of photoperiod on puberty in the male lamb, using a more precise indicator of reproductive activation--the decreased sensitivity of the hypothalamo-pituitary axis to inhibitory steroid feedback leading to increased LH secretion. To test whether photoperiod can influence the onset of neuroendocrine sexual maturation in male lambs, this study compared the timing of the decrease in sensitivity to inhibitory steroid feedback in two groups of males under opposite photoperiodic conditions. Eight males were reared indoors from 2 wk of age under conditions simulating the natural increasing and decreasing day lengths around the summer solstice; an additional 7 males were exposed to a reversed simulated natural photoperiod in which the changes in day length were amplified and accelerated relative to outdoor conditions. Both groups of lambs were castrated and received s.c. implants of Silastic estradiol capsules to provide a constant steroid feedback signal. The timing of reduction in sensitivity to estradiol negative feedback, measured as a sustained increase in circulating of LH above 1.0 ng/ml, was used to define neuroendocrine sexual maturity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878439 TI - In vitro maturation of ovarian oocytes from unstimulated rhesus monkeys: assessment of cytoplasmic maturity by embryonic development after in vitro fertilization. AB - One-hundred and sixty-six cumulus-enclosed oocytes, obtained from ovaries of unstimulated rhesus monkeys, were subjected to six different treatments in vitro- two types of media (simple = TALP; complex = CMRL) x three levels of gonadotropins (none, FSH, FSH + hCG)--to assess their ability to undergo maturation, fertilization, and embryo development. A summary of development in culture for all experimental treatments is as follows: 58% of oocytes underwent germinal vesicle breakdown; 37% extruded a first polar body; 17% had more than one pronucleus and/or two polar bodies after insemination (i.e., were activated/fertilized); and 12% cleaved (i.e., developed) to at least the 2-cell stage in vitro. Of 45 oocytes incubated only in medium (either simple or complex) without gonadotropins, only 3 were activated/fertilized (6.7%), and only one embryo developed to at least the 2-4-cell stage (2.2%). There were no differences between oocytes incubated with only FSH and oocytes incubated with FSH + hCG. Activation/fertilization (20.7% vs. 6.7%) and embryo development (greater than or equal to 2 cells; 15.7% vs. 2.2%) were significantly higher in treatments with than without gonadotropin supplementation. There were no statistically significant differences attributable to incubation in different media during oocyte maturation. Cumulus-enclosed oocytes recovered from unstimulated ovaries of rhesus monkeys can resume maturation during culture in vitro, as shown by their ability to be fertilized and by the cleavage in vitro of the resultant zygotes. PMID- 1878440 TI - Slowed transcription and rapid messenger RNA turnover contribute to a decline in synthesis of ovine trophoblast protein-1 during in vitro culture. AB - Ovine trophoblast protein-1 (oTP-1) is produced in massive amounts by conceptuses during the Day-12-20-period of early pregnancy. The rate of production of oTP-1 declines during culture of conceptuses, however, suggesting a role for critical intrauterine factors for continued production. The present study was conducted to define the mechanism responsible for the in vitro decline in oTP-1 synthesis. Over 24 h culture, synthesis of oTP-1 was initially rapid but then declined such that there was little increase in either the protein or its antiviral activity after 12 h. By contrast, the release of total protein into the medium continued at an approximately linear rate for the entire 24-h period of culture. By using in situ hybridization to tissue sections and dot-blot analysis of tissue extracts with labeled cDNA probes, it was shown that the quantity of oTP-1 mRNA fell 3- to 5-fold during culture, whereas the amount of actin mRNA remained relatively constant. To determine whether this selective fall in levels of oTP-1 mRNA resulted from decreased transcription rate and/or high turnover rate of existing mRNA, conceptuses were either provided continuously with [3H]uridine for 24 h or labeled for 9 h and then exposed to medium enriched in unlabeled uridine and cytidine for a further 15 h. Specific incorporation of 3H into oTP-1 mRNA was assessed by hybridization to excess oTP-1 cDNA immobilized on nitrocellulose membranes. In the continuous labeling study, 3H in total RNA increased at an approximately linear rate for at least 18 h, whereas the content of 3H in oTP-1 mRNA peaked at 9 h and declined about 10-fold by 24 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878441 TI - Drug-induced disturbances of carbohydrate metabolism. PMID- 1878442 TI - Drug-induced hypertension. PMID- 1878443 TI - Toxicity of comfrey. PMID- 1878444 TI - Toxicology of oximes used in treatment of organophosphate poisoning. PMID- 1878445 TI - Blood interactions with novel polyurethaneurea hydrogels. AB - The influence on blood of polyurethaneurea hydrogels in vitro was investigated based on poly(ethylene oxide). A hydrogel was compared with the regenerated cellulose membrane Cuprophan in terms of complement activation, as determined by measurement of C3a concentration. The hydrogel induced less complement activation and the presence of poly(ethylene oxide) is likely to be beneficial to platelet reactivity. The ability to vary the polymer composition and the solubility of the polymers in organic solvents makes the polyurethaneurea hydrogels strong candidates for composite biomaterials. PMID- 1878446 TI - Interaction between phospholipids and biocompatible polymers containing a phosphorylcholine moiety. AB - Random and block copolymers containing a phospholipid polar group in their side chain were synthesized by the copolymerization between 2-methacryloyloxyethyl phosphorylcholine and styrene. These copolymers showed amphiphilic character, especially poly(methacryloyloxyethyl phosphorylcholine-block-styrene) formed stable polymer micelles in water. The interaction between natural phospholipid, dipalmitoylphosphatidylcholine and methacryloyloxyethyl phosphorylcholine copolymers was investigated. The amount absorbed of dipalmitoylphosphatidylcholine from its liposomal solution on to the poly(methacryloyloxyethyl phosphorylcholine-co-styrene) surface increased with increase of methacryloyloxyethyl phosphorylcholine composition. Moreover, when poly(methacryloyloxyethyl phosphorylcholine-block-styrene) was added to dipalmitoylphosphatidylcholine solution, organization of dipalmitoylphosphatidylcholine molecules and stabilization of bilayer structure of dipalmitoylphosphatidylcholine liposome were found. This means that methacryloyloxyethyl phosphorylcholine moieties in the copolymer have a strong affinity to dipalmitoylphosphatidylcholine molecules. The blood compatibility of methacryloyloxyethyl phosphorylcholine copolymers was also investigated with particular attention to the aggregation ability of platelets after contacting methacryloyloxyethyl phosphorylcholine copolymers; this ability decreased when platelets were put in contact with polymers without a methacryloyloxyethyl phosphorylcholine moiety. On the other hand, aggregation ability remained at almost the same level to that of original platelets after contact with methacryloyloxyethyl phosphorylcholine copolymers. From these findings, we concluded that methacryloyloxyethyl phosphorylcholine copolymers show excellent blood compatibility due to adsorption of lipids from plasma and the formation of an organized adsorption layer of lipids on the surface of the methacryloyloxyethyl phosphorylcholine copolymers. PMID- 1878447 TI - New surface modification for Ti-6Al-7Nb alloy: oxygen diffusion hardening (ODH). AB - PVD-TiN coating and N+ implantation of Ti-6Al-7Nb alloy resulted in surface hardening to a depth of less 3 microns. The new oxygen diffusion hardening (ODH) treatment increased the hardness gradually to 50 microns. PUD-TiN showed an improvement in the tribological properties, while N+ implantation increased the PE wear rate. The wear rate of the ultrahigh-molecular-weight as well as the friction coefficient were reduced to one-half of the values achieved with the combination of CoCrMo-alloy when paired against the ODH-treated surface. In pairing with ZrO2-containing bone cement the ODH-treated surface showed only a minimal reaction. PMID- 1878448 TI - Adhesion of endothelial cells and adsorption of serum proteins on gas plasma treated polytetrafluoroethylene. AB - From in vitro experiments it is known that human endothelial cells show poor adhesion to hydrophobic polymers. The hydrophobicity of vascular prostheses manufactured from Teflon or Dacron may be the reason why endothelialization of these grafts does not occur after implantation in humans. We modified films of polytetrafluoroethylene (Teflon) by nitrogen plasma and oxygen plasma treatments to make the surfaces more hydrophilic. Depending on the plasma exposure time, modified polytetrafluoroethylene surfaces showed water-contact angles of 15-58 degrees, versus 96 degrees for unmodified polytetrafluoroethylene. ESCA measurements revealed incorporation of both nitrogen- and oxygen-containing groups into the polytetrafluoroethylene surfaces, dependent on the plasma composition and exposure time. The thickness of the modified surface layer was approximately 1 nm. The adhesion of cultured human endothelial cells from 20% human serum-containing culture medium to modified polytetrafluoroethylene surfaces with contact angles of 20-45 degrees led to the formation of a monolayer of cells, which was similar to the one formed on tissue culture polystyrene, the reference surface. This was not the case when endothelial cells were seeded upon unmodified polytetrafluoroethylene. Surface-modified expanded polytetrafluoroethylene prosthesis material (GORE TEX soft tissue) also showed adhesion of endothelial cells comparable to cell adhesion to the reference surface. The amounts of serum proteins, including fibronectin, adsorbed from serum-containing medium to modified polytetrafluoroethylene surfaces were larger than those adsorbed to unmodified polytetrafluoroethylene. Moreover, the modified surfaces probably allow the exchange of adsorbed serum proteins with cellular fibronectin. PMID- 1878449 TI - Ion implantation effects on friction and wear of joint prosthesis materials. AB - The literature contains many results from in vitro friction and wear tests for simulating the behaviour of human joint prostheses. However, they are difficult to correlate, even when they are not contradictory. In friction tests, several friction-mechanisms occur when the Ti-6AI-4V titanium alloy rubs against the UHMWPE polyethylene. Corrosion effects which increase wear happen when the 316L stainless steel is used in Ringer's solution. Ion implantation surface treatments have been performed on these three materials. When the operating conditions were optimized, an important reduction of wear and corrosion was observed. The property improvements are due to structural modifications in a thin layer of the materials. PMID- 1878450 TI - Bioactive glass ceramics: properties and applications. AB - Heat treatment of an MgO-CaO-SiO2-P2O5 glass gave a glass ceramic containing crystalline apatite (Ca10(PO4)6O,F2] and beta-wollastonite (CaO,SiO2) in an MgO CaO-SiO2 glassy matrix. It showed bioactivity and a fairly high mechanical strength which decreased only slowly, even under load-bearing conditions in the body. It is used clinically as artificial vertebrae, iliac bones, etc. The bioactivity of this glass ceramic was attributed to apatite formation on its surface in the body. Dissolution of calcium and silicate ions from the glass ceramic was considered to play an important role in forming the surface apatite layer. It was shown that some new kinds of bioactive materials can be developed from CaO,SiO2-based glasses. Ceramics, metals and organic polymers coated with bone-like apatite were obtained when such materials were placed in the vicinity of a CaO,SiO2-based glass in a simulated body fluid. A bioactive bone cement which was hardened within 4 min and bonded to living bone, forming an apatite, was obtained by mixing a CaO,SiO2-based glass powder with a neutral ammonium phosphate solution. Its compressive strength reached 80 MPa comparable to that of poly(methyl methacrylate) within 3 d. A bioactive and ferromagnetic glass ceramic containing crystalline magnetite (Fe3O4) in a matrix of CaO,SiO2-based glassy and crystalline phases was obtained by a heat treatment of a Fe2O3-CaO.SiO2-B2O3-P2O5 glass. This glass ceramic was shown to be useful as thermoseeds for hyperthermia treatment of cancer. PMID- 1878451 TI - Glass ceramic approach to controlling the properties of a glass-ionomer bone cement. AB - Glass-ionomer dental cements have potential as bone cements in joint replacement surgery. However, commercially available glasses used in dental cements suffer from the loss of fluorine during the melting procedure and from phase separation of the glass upon quenching, giving rise to inter- and intra-batch variation. A model glass was examined in which minimal loss of fluorine is observed. This results in a glass whose composition is reproducible between batches. This glass will crystallize both above and below the glass transition temperature following heat treatments. Cements can be produced whose properties vary with the degree of crystallinity of the glass-ceramic. A commercial glass was also examined and was found to crystallize to an apatite phase. PMID- 1878452 TI - Reactions of cells at implant surfaces. AB - The surface of implants is an important parameter in host-implant integration. Several strategies can be used to obtain integration, such as the application of grooves or pores at the implant surface. Most of these surface alterations, however, will lead to an increase of total implant surface area which might influence the inflammatory response to an implant. As far as integration with bone is concerned several biomaterials have been successful in mimicking this material, by having similar crystals at their surface (calcium phosphate ceramics) or by containing a certain amount of calcium and phosphorus. Polyactive, a poly(ethylene oxide)-poly(butylene terephthalate) segmented copolymer, also possesses favourable integration properties with bone, but initially lacks calcium and phosphorus. It is proposed that the application of hydrogels as biomaterial may add a new dimension to integration capacity. PMID- 1878453 TI - Modulation of the membrane surrounding particulate cement and polyethylene in the rabbit tibia. AB - Twenty-nine mature New Zealand white, female rabbits were divided into four groups. Using sterile technique, a 6 mm drill hole was made in the tibia 1 cm distal to the knee joint. The marrow was scooped out underneath the hole. The right tibia received Simplex particulate cement polymer (PMMA) (groups 1 and 2) or polyethylene particles (UHMWP) (groups 3 and 4). The left leg functioned as a prepared but non-implanted control. All animals were fed a standard diet; those in groups 1 and 3 received plain water, while groups 2 and 4 drank water in which sodium naproxen was dissolved (1.375 mg/ml). Animals were killed after 16 wk. The implant area was harvested and grown in tissue culture. The cumulative collection of tissue culture supernatants over 3 d was assayed for prostaglandin E2 (PGE2) via radioimmunoassay. PGE2 production was significantly higher in the membrane harvested from the right side containing particulate cement with no sodium naproxen (group 1) compared with controls (P less than 0.05). The ratio of PGE2 values for the right divided by the left side yielded higher values in group 1, compared with groups 2, 3 or 4 (P less than 0.01). Previous studies have suggested that particulate debris and PGE2 production are associated with arthroplasty loosening. This experiment has demonstrated that PGE2 production by the membrane surrounding particulate debris can be suppressed by the administration of oral sodium naproxen. Because non-steroidal anti-inflammatory drugs are known to inhibit prostaglandin synthesis in man, these agents may prove useful in retarding the bone loss associated with early prosthetic loosening. PMID- 1878454 TI - Interactions of copolymeric poly(glyceryl methacrylate)-collagen hydrogels with neural tissue: effects of structure and polar groups. AB - In a previous study we developed copolymeric glyceryl methacrylate-collagen hydrogels for implantation in surgical lesions of the rat brain. Such materials provide porous matrices that can serve as support systems for oriented growth of scar tissue and axonal growth. In the present work, we have investigated the effect of structural modifications (studied by mercury porosimetry) of polymeric matrices and the effect of polar groups on the response of the brain tissue. The findings show that the fractional porosity and the pore size distribution of matrices are critical for tissue ingrowth and that negative charges, i.e. carboxylic acid groups, incorporated in the polymer have a strong influence on reactive astrocytosis. PMID- 1878455 TI - Electrochemical corrosion behaviour of hydroxyapatite-glass-titanium composite. AB - To determine whether hydroxyapatite(HA)-containing glass would exhibit the desired stability and activity under in vivo conditions, electrochemical corrosion behaviour of HA-glass-titanium composites was estimated by anodic polarization measurement in a simulated body fluid, 0.001 N HCl solution, 0.1 M NaCl solution, 0.1% albumin solution, and 0.1% fibrinogen solution. Potentiostatic anodic polarization measurements were made from each rest potential to +2 V versus s.c.e. with an increasing rate of 1 mV/s. Anodic polarization curves for pure titanium provided typical passive corrosion behaviour in HCl solution. The breakdown potentials were +1.4 V in HCl solution and +1.2 V in other solutions. The glass-coated specimens showed extremely low current density, less than 0.001 microA/cm2, from rest potential to about +1.8 V, and showed a slight increase in current density over +1.8 V. The polarization curves for the HA-glass-Ti composites were quite different from those for Ti and the glass-coated specimens. The current density for 50-90% HA -glass-Ti composites increased drastically from less than 0.001 to 10 microA/cm2 around rest potential (about -0.5 V), and continued to rise slightly up to +2 V. Addition of protein in NaCl solution exhibited little effect on anodic polarization curves for Ti and HA-glass-Ti composites. PMID- 1878456 TI - In vitro degradation of a PHB/PHV copolymer and a new technique for monitoring early surface changes. AB - The use of polyhydroxbutyrate and its copolymers as degradable materials for surgical use is showing increasing promise due to their long degradation profile. Of considerable interest were the interfacial changes and their role in affecting the overall or bulk degradation pattern. The role of pH and its effect on the degradation pattern were examined as polymer degradation significantly altered, depending on whether it was subjected to an alkaline or an acidic medium. In vitro surface changes were monitored using two techniques (scanning electron microscopy and goniophotometry); bulk changes were monitored by gravimetric, mechanical and molecular weight techniques. It was concluded that the bimodal molecular weight distribution plays a significant part in the degradation pattern and that this pattern is also considerably altered by pH. PMID- 1878457 TI - Micro-observation and characterization of bonding between bone and HA-glass titanium functionally gradient composite. AB - Bioactive composite implants consisting of hydroxyapatite (HA)-glass (G) ceramic layer and Ti-6AI-4V alloy, so-called HA-G-Ti functionally gradient implant, were provided for investigating the bonding behaviour of bone to the implant in vivo. The HA-G-Ti composites were implanted in femur and tibia of dog for various periods (1-12 month). Microstructural appearance of the interface between bone and the HA-G coating layer as well as the transverse sections of the HA-G coating layer and further apposition of bone to the implant have been studied in detail with SEM. The ingress of collagen fibres into the HA-G coating layer and the deposit of apatite on the collagen fibres and HA crystal grains being containing within the HA-G coating layer have been observed. Radiographical experiments indicate that the reparative process in the bone tissue surrounding the implants is markedly ahead even at one month after implantation. FT-IR measurement and X ray diffraction were carried out for studying the characterization of the calcified bone matrix around the implants and the new bone proliferated along the HA-G-coated face (surface). PMID- 1878458 TI - Rat peritoneal immune response to carbon fibre reinforced epoxy composite implants. AB - The aim of this paper was to evaluate the histocompatibility of differently cured carbon fibre reinforced epoxy composites, studying their potential to induce an intolerance reaction in neighbouring tissues after peritoneal implantation in the rat. According to the microscopic and scanning electron microscope findings, the inductive capacity to generate connective tissue and cellular reaction was greatest in the partially cured material compared to the fully cured material. In addition, only the partially cured material implants appeared totally coated by macrophages at various stages of activation. The differences in the cellular reactions and scar tissue deposition in the interstices of these two composites are probably related to the chemical surface properties rather than to the structural characteristics of the materials. PMID- 1878459 TI - Partially biodegradable polyacrylic-polyester composites for internal bone fracture fixation. AB - New partially resorbable composite formulations based on components used in surgery were synthesized in rod form (length 15-20 mm, diameter 4 mm). The biostable components were poly(methyl methacrylate) in hydrophobic implants and poly(2-hydroxy ethyl methacrylate) in hydrophilic ones. The biodegradable components were commercially available suture yarn made from poly (alpha-hydroxy esters): polyglycolide, a polyester derived from glycolic acid; and a copolyester of glycolic and lactic acids, polyglactin 910. Biodegradation in phosphate buffered solution at pH 7.0 and 37 +/- 0.5 degrees C was analysed gravimetrically. There was no measurable loss of mass after treatment for 20-25 d. Composite microstructure was examined by phase-contrast, cross-polarized light microscopy. PMID- 1878460 TI - Calcification of soft tissue employed in the construction of heart valve prostheses: study of different chemical treatments. AB - Biological heart prostheses present medium and long-term problems, owing to progressive deterioration and calcification of the tissue. To study the latter problem, we compared the effectiveness of anticalcification treatments in calf pericardium samples implanted into female Wistar rats after the following procedures: group I, control group (glutaraldehyde 0.2%); group II, proteoglycans group, group III, control group (glutaraldehyde 0.625%); groups IV and V, subjected to lipid removal with chloroform/methanol and SDS; group VI, pericardial tissue treated with 0.1 M AI3+ for 24 h; and group VII, chemical treatment with 0.1 M La3+ for 24 h. Positive results were obtained with lipid removal and chemical treatment with AI3+. The selective extraction of proteoglycans resulted in considerable accumulation of calcium salts in the tissue. PMID- 1878461 TI - Osteogenic potential of culture-expanded rat marrow cells as assayed in vivo with porous calcium phosphate ceramic. AB - It has been established that, when whole marrow is introduced into porous calcium phosphate ceramic, bone forms on the walls of the pores. To extend earlier studies, bone marrow cells derived from the femora of inbred rats were introduced into tissue culture and the adherent cells cultivated, mitotically expanded, passaged, harvested, placed in small cubes of porous calcium phosphate ceramics and grafted into subcutaneous sites of syngeneic rats. Marrow-derived, cultured mesenchymal cells introduced into ceramics showed strong osteogenic potential, with bone forming in the pore regions of ceramics as early as 2 wk after implantation. Osteogenesis could be observed after the eighteenth passage. With increasing passage number, the initiation of osteogenesis and the apparent rate of bone formation declined and the course of osteogenesis was delayed. In the future, it may be possible to culture marrow cells as a source for reparative cells for implantation back into autologous in vivo sites. PMID- 1878462 TI - Influence of surface texture of polymeric sheets on peripheral nerve regeneration in a two-compartment guidance system. AB - Synthetic guidance channels are useful tools to study the mechanisms underlying peripheral nerve regeneration. In the present study, the lumen of silicone elastomer tubes was divided into two compartments by a polymer strip 10 mm long placed along the tube length. The influence of varying the surface texture of hydrophilic and hydrophobic polymer strips on the morphology of the regenerated neural tissue was analysed. Hydrophilic nitrocellulose (NC) and hydrophobic polyvinylidene fluoride (PVDF) films with smooth (S-NC and S-PVDF) or rough (R NC, R-PVDF) surface texture were used. Five channels of each type were used to repair transected rat sciatic nerves and analysed after 4 wk. Tissue strips bridged the nerve stumps in all R-NC and R-PVDF tubes, in five of the S-NC and three of the S-PVDF tubes. In R-NC and R-PVDF tubes, bell-shaped tissue adhering to the polymer strip was observed, whereas in S-NC and S-PVDF tubes round, free floating nerve cables were seen. All the cables contained myelinated and unmyelinated axons and Schwann cells grouped in microfascicles and surrounded by an epineurial layer. For both rough strips, the initial cell layer consisted of macrophages adhering to the polymer surface. The epineurial nerve tissue contacting the rough surface was significantly thinner for PVDF compared with NC strips. No difference in epineurial thickness was observed for nerves facing the silicone tube or for smooth NC and PVDF strips. S-PVDF tubes contained significantly more myelinated axons than S-NC tubes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878463 TI - Modern metal processing for improved load-bearing surgical implants. AB - A review of modern methods for preparing metallic alloys that could be useful for the fabrication of load-bearing metallic biomaterials is presented. The use of rapid solidification processing and surface modification of metals by ion implantation or surface coatings and variations thereof is used currently for the formation of novel metallic alloys in other high-tech fields, notably the optoelectronics industry. Further studies to explore potential benefits for surgical implant fabrication through the application of these technologies is recommended. PMID- 1878464 TI - [Non-Hodgkin's lymphoma with low degree of malignancy]. PMID- 1878465 TI - [Chronic myeloid leukosis. Current status]. PMID- 1878466 TI - [Role of aluminum in osteodystrophy and anemia in chronic renal failure]. PMID- 1878467 TI - [Erythropoietin in the treatment of anemia in chronic renal insufficiency]. PMID- 1878468 TI - [Cyclosporin in the treatment of idiopathic nephrotic syndrome]. PMID- 1878469 TI - [Endoscopic therapy in the digestive system]. PMID- 1878470 TI - [Neurologic disorders in alcoholism]. PMID- 1878471 TI - [Neurologic manifestations of vasculitis]. PMID- 1878472 TI - [Digital angiography in the central nervous system]. PMID- 1878473 TI - [Community-acquired pneumonia]. PMID- 1878474 TI - [Current status of osteomyelitis]. PMID- 1878476 TI - [Silent ischemic cardiopathy]. PMID- 1878475 TI - [Spontaneous bacterial peritonitis in the cirrhotic patient]. PMID- 1878477 TI - [Arterial hypertension and insulin resistance]. PMID- 1878478 TI - [Thrombolysis in pulmonary thromboembolism]. PMID- 1878479 TI - [New findings on the etiopathogenesis of diabetes mellitus]. PMID- 1878480 TI - [Hypertension of endocrine origin]. PMID- 1878481 TI - [Therapeutic approach in hyperthyroidism]. PMID- 1878482 TI - [Reactive arthritis]. PMID- 1878483 TI - [Pulmonary involvement in HIV infection]. PMID- 1878484 TI - Antiarrhythmic effect of L-propionylcarnitine in isolated cardiac preparations. AB - The effects of L-propionylcarnitine on reperfusion-induced ventricular arrhythmias were studied in isolated hearts from spontaneously hypertensive rats. During reperfusion, 60% (n = 15) of the hearts from control spontaneously hypertensive rats hearts developed irreversible ventricular fibrillation. In contrast, irreversible ventricular fibrillation did not occur in hearts from normotensive Wistar Kyoto rats (n = 11, p less than 0.01). In a second group of spontaneously hypertensive rats, the addition of 10(-6) M L-propionylcarnitine to the medium during ischemia and reperfusion reduced the incidence of irreversible ventricular fibrillation to 14% (n = 14, p less than 0.05 versus control spontaneously hypertensive rats, NS versus Wistar Kyoto rats). Concentrations of L-propionylcarnitine from 10(-6) to 10(-2) M were tested on isolated guinea pig papillary muscles using microelectrodes. Resting potential, action potential amplitude, action potential duration and active tension were not modified by L propionylcarnitine; and 10(-3) M L-propionylcarnitine did not influence the oscillatory afterpotentials induced by digitalis. We conclude that reperfusion ventricular arrhythmias are more severe in spontaneously hypertensive rats than in Wistar Kyoto rats and that the antiarrhythmic effect of L-propionylcarnitine in spontaneously hypertensive rats is mediated by myocardial protection from damage induced by reperfusion. PMID- 1878485 TI - Relation between epicardial electrograms and signal-averaged electrocardiograms after acute myocardial infarction in dogs. AB - Signal-averaged electrocardiograms allow the non-invasive detection of late potentials which represent locally delayed conduction in the myocardium. To validate this method, it is necessary to compare the signal-averaged data with electrograms recorded directly from the heart. However, the studies performed to date involve only a consecutive collection of the invasively and non-invasively obtained data. To obtain a more direct comparison, we examined this relation at operation by simultaneous epicardial and signal-averaged measurements. Acute infarction in animals was chosen, because the ischemic area is a zone of delayed conduction whose presence can be verified in a signal-averaged electrocardiogram. For this purpose, the left anterior descending artery, proximal of large septal and diagonal branches, was tied off in nine mongrel dogs after thoracotomy. Before infarction, a signal-averaged electrocardiogram was recorded from the body surface. At the same time, epicardial electrograms were performed using bipolar electrodes both from the supply area of the left anterior descending artery and from that of the circumflex artery. Five minutes after coronary ligation, both the epicardial measurements and the signal-averaged electrocardiogram were repeated on the open thorax. Before occlusion of the left anterior descending artery, narrow activation complexes occurred in general in the epicardial electrograms and no late potentials were recorded in any dog by the signal averaged electrocardiogram. Five minutes after coronary ligation, fractionated and prolonged electrograms occurred in the epicardial recordings from the ischemic zone, while the activation complexes in the uninfarcted supply area of the circumflex artery remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878486 TI - Reflex effects of descending colon distension on coronary blood flow in anesthetized dogs. AB - To find out whether distension of the descending colon reflexly affects coronary blood flow, experiments were performed in nine dogs anesthetized with pentobarbitone. The descending colon was isolated between ligatures and distended with warm Ringer solution at a steady intraluminal pressure. Arterial blood pressure was prevented from changing by withdrawing blood from the left femoral artery. In two of the nine dogs the arterial blood pressure was also kept constant by tightening a plastic snare round the thoracic aorta. The reflex increase in heart rate was prevented by atrial pacing. Distension of the descending colon at constant heart rate and arterial blood pressure always caused a decrease in mean coronary blood flow, amounting to 2.44 +/- 1.8 ml/min (mean +/ SD), equal to a percent decrease of 14.3 +/- 10.5. This response was completely abolished by section of the hypogastric nerves, thus demonstrating that a reflex mechanism is involved. PMID- 1878487 TI - Temporal relations of the endocrine response to exercise. AB - We have followed the hormonal response to exercise in twelve normal males cycling at a constant moderate load for ten minutes. Plasma concentrations of a variety of hormones were measured at set times before and during exercise and for twenty minutes afterward. The plasma concentration of norepinephrine and epinephrine and plasma activity of renin rose to a maximum at the end of exercise and then declined. The plasma concentrations of neurotensin and atrial natriuretic peptide followed a similar course. Plasma vasopressin rose to a peak at the end of exercise and then fell transiently below the initial value ten minutes after exercise. The plasma concentrations of aldosterone, prolactin and adrenocorticotropin increased during exercise but continued to do so, reaching a peak at ten minutes after exercise. Plasma growth hormone increased during exercise and continued to increase throughout the period of twenty minutes' recovery. Cortisol did not change during exercise but rose progressively during the recovery period. Plasma concentrations of glucagon did not change while that of insulin decreased during exercise. The plasma concentration of bombesin slowly increased during exercise and declined during recovery, reaching a basal value 10 minutes later. PMID- 1878488 TI - A comparison of contractile function between papillary muscles and isolated myocytes from the same human hearts. AB - The contractile function in response to increasing extracellular calcium and isoprenaline has been investigated using papillary muscles from seven human hearts (failing and non-failing) obtained at the time of transplant. Myocytes have been enzymatically isolated from adjacent myocardium, and their contractile characteristics measured in parallel to those of the intact papillary muscle. Similar experiments were performed on rabbit hearts, but in this case separate animals were used for the papillary muscles and cells. For human myocardium, the EC50 (concentration for half-maximal effect) for calcium, and the percentage increase in amplitude between basal (1.3mM) and maximally activating calcium, was similar between papillary muscle and cells. Variability of absolute responses was 4-5 times greater for papillary muscle than for myocytes. Isoprenaline accelerated the time to peak tension, time to 50% relaxation and time to 90% relaxation in papillary muscle; a similar effect on shortening was seen for time to peak tension and time to 50% relaxation in cells. Time to peak tension and time to 50% relaxation were not significantly different between the human preparations with isoprenaline, but the time to 50% relaxation with high calcium was faster for myocytes than for papillary muscle (p less than 0.05). Isoprenaline induced after-contractions in some cells, prolonging the time to 90% relaxation. This was not observed in papillary muscle preparations. Papillary muscles were less sensitive to the stimulatory effects of isoprenaline than cells taken from the same hearts. EC50 values were higher (p less than 0.05) and increases in contraction were lower (p less than 0.05) in whole tissue. This difference between cells and papillary muscle was not seen in rabbit hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878489 TI - NADPH oxidase activity in the monocytes and neutrophils of patients with rheumatic fever. AB - The enzyme NADPH oxidase is involved in the production of oxygen free radicals. We measured its activity in neutrophils and monocytes obtained from patients with acute rheumatic fever, chronic rheumatic heart disease, acute streptococcal pharyngitis and normal controls. Follow up studies were made at 15 days, 3 months and 6 months. Streptococcal membrane antigen, carbohydrate antigens and latex were used to stimulate the oxidative activity in the neutrophils and monocytes. These three agents caused a significant increase in the enzyme activity of the phagocytes of patients with acute rheumatic fever and chronic rheumatic heart disease (p less than 0.001) but not in acute pharyngitis. Maximal NADPH oxidase enzyme activity was observed in patients with acute rheumatic fever. During the follow-up, there was a significant decline in the enzymatic activity in patients with acute rheumatic fever but not in those with chronic rheumatic heart disease. Enzymatic activity was greater when the phagocytic cells were triggered with membrane as compared to carbohydrate antigen and latex in all the groups and at all intervals. The enzymatic response of neutrophils and monocytes was similar although the magnitude of the NADPH oxidase activity was significantly higher in neutrophils than in monocytes. PMID- 1878490 TI - Vulvar malignancy. AB - Treatment of invasive vulvar malignancy has become more individualized during the past decade. In the past, radical vulvectomy with bilateral inguinofemoral lymphadenectomy was the standard therapy for invasive squamous cell carcinoma and melanoma of the vulva. This is no longer always the case. The treatment of stage I and stage II invasive squamous cell carcinoma of the vulva has become more individualized. Less radical surgery appears to produce the same results as ultraradical surgery. Wide local excision of early lesions associated with ipsilateral lymph node dissection appears to be adequate therapy in many cases. Likewise, treatment of early melanoma (0.75 mm in thickness) can be managed by wide local excision with or without groin dissection of the ipsilateral side. This more conservative approach has resulted in significantly fewer postoperative complications and has improved the self-image of many women undergoing treatment for vulvar malignancy. PMID- 1878491 TI - Maternal/fetal medicine. PMID- 1878492 TI - Gynecologic oncology. PMID- 1878493 TI - Drug therapy during pregnancy. AB - Fetal dysmorphic syndromes have been described with exposure to most commonly used anticonvulsants, most recently carbamazepine (Tegretol, Ciba-Geigy, Basel, Switzerland). Fetal genetic susceptibility may determine which infants are affected. Long-term use of heparin in pregnancy may cause significant osteoporosis, which appears to be reversible. Pharmacokinetic studies of ritodrine have resulted in recommendations for more appropriate infusion regimens, including a role for intramuscular therapy for patients undergoing maternal transport. Nifedipine shows promise as a tocolytic with fewer side effects than ritodrine but equivalent efficacy. Indomethacin is also an effective tocolytic, and clinically significant side effects have not been seen with 48 hours or less of treatment. Indomethacin has also been used successfully for treatment of polyhydramnios. PMID- 1878494 TI - Medical disorders in pregnancy, including hypertensive diseases. AB - Medical disorders, including hypertensive diseases, may exist prior to pregnancy (eg, connective tissue diseases, chronic hypertension, thyroid disease) or may manifest themselves for the first time during pregnancy (eg, gestational diabetes, gestational hypertension). The outcome for a particular pregnancy will depend on the nature of the disease, the severity of the disease process at onset of pregnancy, and the quality of obstetric and medical management used. Management of pregnancies with preexisting medical disorders should begin before conception. These women should be evaluated to determine the severity of the disorder and to establish the presence of possible target organ damage. In addition, they should be counseled regarding the potential adverse effects of the disease on pregnancy outcome and the effects of pregnancy on their disease. These women should be instructed regarding the importance of early onset of prenatal care and compliance with frequent prenatal visits. PMID- 1878495 TI - The very tiny baby, multiple births, and other questions about preterm deliveries. AB - The progressive change of the limit of viability accepted for very preterm babies has resulted in a progressive improvement of survival, but also in costs for days spent in intensive care and for numbers of severely handicapped babies. Multiple births, including twins but especially triplets and quadruplets, result in severely premature births, high death rates, high costs, and severe risk of handicap. As most supermultiple pregnancies are the result of ovulation-inducing drugs, this rise has to be limited. More than acute care, prevention is the only good solution, from both an ethical and an economical standpoint. PMID- 1878496 TI - Fetal assessment in postterm pregnancy. AB - There is considerable disagreement over the management of postterm pregnancies. The main controversy is whether to adopt a policy of routine induction or one of selective induction allied to frequent fetal surveillance. Current evidence suggests that routine induction at 42 weeks' gestation does not increase the risk of instrumental delivery or cesarean section. To adopt the former approach, it is important that gestation is confirmed by early ultrasound examination, which has reduced the true incidence of postterm pregnancy to less than 6%. There have been no recent significant advances regarding methods of fetal surveillance in the postterm pregnancy. PMID- 1878497 TI - Cervical malignancies. AB - Articles published between August 1989 and July 1990 related to squamous cell carcinoma of the cervix are reviewed. A discussion of new histopathologic findings is given along with current hormonal receptor studies. The host immunocompetence with an immunologic staging system is presented. Recent studies of the clinical application of the serum squamous cell antigen are reviewed. The finding of positive pelvic nodes at the time of a radical hysterectomy is investigated within literature review. The advantages and risks of radical surgery, radiation therapy, and combined treatments are presented with no clear conclusion being found. Advanced or recurrent cervical cancers may be treated with radiation, chemotherapy, or ultraradical surgery depending on the clinical setting. Early studies of combination therapies are given for these difficult situations. PMID- 1878498 TI - Breast malignancy. AB - Risks associated with oral contraceptive use have been shown for women who begin using them before age 25 and before their first full-term pregnancy. The effectiveness of chemoprevention is being studied. Screening may reduce mortality by 30% in women aged 50 to 69. Breast-conserving lumpectomy is indicated for small tumors. In some postmenopausal node-positive patients, a combination of hormonal and chemotherapy may be useful. In metastatic breast cancer, dose intensification of chemotherapy has been investigated. Palliative treatment involves tamoxifen. Analysis of steroid hormone receptor status involves fine needle aspiration, enzyme immunoassay, and a new autoradiographic procedure using radiolabeled estrogens. Prognostic factors under study include oncogene amplification, urokinase plasminogen activator level, expression of growth factors and growth factor receptors, proliferation parameters such as ploidy and S-phase fraction, mutations, and cathepsin D levels. PMID- 1878499 TI - Ovarian malignancy. AB - Despite major advances in the management of ovarian cancer over the last two decades, overall prognosis remains poor. Attempts to improve early detection by screening with sonography and tumor markers have thus far been unsuccessful. The tumor marker CA-125 has, however, proven to be useful in indicating responsiveness to chemotherapy, and in turn predicts survival. Patients with well or moderately well-differentiated stage IA-1 and IB-1 ovarian cancers have excellent survivals and do not require adjuvant therapy. In contrast, patients with poorly differentiated stage I and II tumors have a 20% failure rate and should be treated. Carboplatinum, with its favorable spectrum of toxicities, is becoming the platinum analogue of choice. Taxol is a new active agent for ovarian cancer and may prove efficacious in combination with platinum for ovarian cancer. Second-look surgery should no longer be performed routinely. Recent data suggest that tumor heterogeneity may compromise immunotherapy that targets cell surface antigens. PMID- 1878500 TI - Vaginal malignancy. AB - Various malignant neoplasms, either primary or secondary, can affect the vagina. The most common primary malignant tumors of the vagina are squamous cell cancers; however, they are among the most uncommon of all primary gynecologic cancers. Vaginal intraepithelial neoplasia is being diagnosed with increasing frequency and continues to be a challenging problem. Laser therapy and topical 5 fluorouracil are the preferred treatment methods reported in the current literature. Invasive cancer of the vagina is primarily a disease of the older woman and presents most commonly with abnormal bleeding. Radiotherapy continues to be used as external beam or intracavitary treatment for the majority of women with this problem. Vaginal melanomas are a special group of vaginal neoplasms and appear to have a much poorer prognosis than their vulvar counterparts. It would appear that early diagnosis is the most favorable factor affecting outcome, with treatment modality being secondary. PMID- 1878501 TI - Neonatal and infant problems of low birth weight. AB - New therapies are being developed to improve survival of low-birth-weight infants, especially those weighing less than 1000 g. The most exciting new development is the use of surfactant replacement therapy for treatment of respiratory distress syndrome. This therapy results in less severe acute lung disease and has decreased mortality from respiratory distress syndrome. As more infants survive, consideration of long-term sequelae including chronic lung disease and neurologic outcome are of paramount importance. This review covers strategies for prevention and treatment of respiratory distress syndrome (including surfactant replacement). New and evolving treatments for amelioration of chronic lung disease and issues in neurologic outcome for the low-birth-weight infant (including prevention of intraventricular hemorrhage) are addressed. PMID- 1878502 TI - Endometrial malignancy. AB - This article reviews published papers on endometrial carcinoma from August 1989 to July 1990. The hypothesis of two different pathogenic types of endometrial carcinoma, which are well correlated with favorable and unfavorable prognosis, has been established. The prognosis for patients under 21 years of age with well differentiated endometrial carcinoma is excellent; for them, a conservative, fertility-preserving treatment is possible. The characteristics of carcinomas with unfavorable prognoses are also discussed. These prognostic factors are measurable in tissue from preoperative curettage. Measurement of myometrial invasion by vaginal sonography and nuclear magnetic resonance imaging is possible with a high degree of safety preoperatively as well. At least intraoperatively, an exact measurement of depth of invasion can be obtained by frozen-section diagnosis. In an optimal preoperative examination, it should be possible to select patients with a high rate of metastases for intraoperative lymphadenectomy. For adjuvant postoperative therapy, percutaneous radiotherapy is indicated in high-risk patients in whom no optimal lymphadenectomy has been done. Vaginal irradiation, however, used in all cases up until now, is known to bring about more local complaints. Adjuvant progestagen treatment in low-risk patients is dangerous because it can cause a higher rate of cardiovascular disease and does not reduce death by recurrent disease. The profit for high-risk patients seems very small. Analysis of endometrial carcinoma tissue shows a high rate of receptors for luteinizing hormone-releasing hormone and analogues. Adjuvant chemotherapy in high-risk patients until now has been without measurable effect. PMID- 1878503 TI - Barrier contraceptives, spermicides, and periodic abstinence. AB - Although barrier contraceptives were among the first methods of preventing unwanted pregnancy ever described for human use, with the advent of the non coitally related oral contraceptives and intrauterine devices, they gradually fell into relative disuse. However, for a variety of reasons, this is no longer the case. There is a renewed interest in these techniques both as a major form of birth control and also as our best protection against the transmission of sexually transmitted diseases, many of which are now occurring in epidemic form. This latter reason has stimulated fresh approaches to both physical barriers and spermicidal agents. In addition, attempts have also been made to assess the true effectiveness of periodic abstinence and ways in which to make its use more accurate and acceptable. PMID- 1878504 TI - Intrauterine devices. AB - Approximately 60 million women use the intrauterine device (IUD) worldwide; however, owing primarily to nonmedical reasons, the IUD is far less popular in the United States. Although the contraceptive mechanism of action is unknown, it appears that spermicidal activity may be important. Overall, the efficacy of the copper devices is quite good, such that the overall lifespan can probably be extended. Possible pelvic infection remains the greatest potential risk, although in properly selected women the risk is quite low. Use of prophylactic antibiotics at the time of insertion may offer additional protection against this risk. Although IUD users may have more nonspecific vaginal inflammation than do other women, the clinical significance is probably limited. Further, users do not appear to have elevated risks for cervical infections. Although menometrorrhagia persists as a potential problem, the mechanism for such bleeding is not well understood. Finally, the retroflexed uterine position does not appear to increase the risk of abnormal outcomes. PMID- 1878505 TI - Combined progestin and estrogen (oral), and other forms of hormonal contraception. AB - This review examines controversies concerning serious side effects of oral contraceptives. Current concerns about the pill are with either relatively small excess risks or with very long-term effects, which need not be small. The main outstanding questions are the effects on cardiovascular disease of lowering doses and the effects on breast cancer of oral contraceptive use at a young age. In the end, the possible effects on breast cancer incidence cause the most concern. It is argued that most epidemiologic studies are too small to reliably detect effects among particular subgroups and it is possibly too soon to know what the long-term effects of using oral contraceptives while young on breast cancer actually are. However, complacency is contraindicated. PMID- 1878506 TI - Experimental methods of contraception. AB - While most new contraceptives currently in development incorporate existing contraceptive agents into new delivery systems, several types of contraceptives with novel mechanisms of action are making steady progress. The antiprogestin mifepristone (better known as RU 486) is being tested as an ovulation inhibitor, as a once-a-month pill, and as a postcoital contraceptive. An antiestrogen, Centchroman (Hindustan Latex, India), is in use in India as a once-a-week, nonsteroidal pill. The development of more potent pituitary gonadotropin antagonists has improved their potential to block ovulation in women and to inhibit spermatogenesis in men (which requires concurrent administration of testosterone). Another promising male contraceptive is an intraluminal vas occlusion plug tested extensively in China that can be removed with no apparent detriment to future fertility. Finally, several types of immunocontraceptives could become the most specific form of fertility control by directing an antibody response against the fertilized or unfertilized egg or against sperm. PMID- 1878507 TI - Abortion. AB - In 1990 abortion literature was characterized by articles relating to 1) the safety of surgical abortion procedures, 2) advances in knowledge and experience with medical abortifacients such as mifepristone (RU 486), and 3) reviews of psychologic and ethical considerations. Although technical methods differ greatly between countries and continents, there is increasing similarity between termination protocols in the United States, the United Kingdom, and Europe. The advent of mifepristone will make this even more so. Surgically, although dilatation and evacuation procedures are far more common in the United States than in other countries, the literature reflects a fine-tuning of analysis and technique, with safety the major consideration. Knowledge about the effectiveness of mifepristone continues to grow, and the effective dose for early first trimester termination appears established. There is increasing evidence that at least in the short term, the negative psychologic sequelae of abortion are infrequent and are inconsequential as a public health issue. PMID- 1878508 TI - Sterilization. AB - Sterilization has become the most widely used method of family planning in both the developed and developing world. This article discusses the importance of presterilization counseling and describes the timing of the procedure, methods of anesthesia, and occlusion techniques (eg, tubal ligation and the use of rings and clips) in female sterilization. Other topics covered in sterilization of women are long-term follow-up and complications, reversal of sterilization, impact of national sterilization policies, and nonsurgical sterilization. The article includes a short section on surgical contraception for men. PMID- 1878509 TI - Investigative procedures in urogynecology. AB - History and physical examination do not always correlate with final urodynamic diagnoses in incontinent women. A large number of diagnostic procedures are available to help the clinician establish the correct diagnosis. The importance of urine culture, Q-tip test, ultrasound, pessary test for potential incontinence, neurophysiologic testing, endoscopy, urethral pressure profiles, stress/pad tests, uroflowmetry, and cystometry are discussed. The physician should understand the importance and limitations of each of the different investigative procedures. PMID- 1878510 TI - Urge incontinence and stress incontinence. AB - Urinary incontinence remains a common problem that adversely affects the quality of life of millions of women. In detrusor instability, treatment measures often lack efficacy or are accompanied by unacceptable side effects. In this review, standard treatments are discussed, together with recent pharmacologic advances and the introduction of newer techniques including maximal electrical stimulation. The nonsurgical treatment options currently available for genuine stress incontinence are considered in the light of recent advances. PMID- 1878511 TI - Choice of operation for genuine stress incontinence. AB - Surgery, the definitive treatment for most patients with genuine stress urinary incontinence, continues to evolve, as does the rationale for choice and application of given operations. The history of surgical progress to the present is well covered by Kohorn (Obstet Gynecol Clin North Am 1989, 16:841-852) and includes those operations that have progressively supplanted the anterior colporrhaphy on which the gynecologist traditionally depended. Emphasis on the secure retropubic placement of the bladder neck has led to the development of a number of modifications of open retropubic cystourethropexy, minimal incision needle suspension techniques, and various sling operations; recently reported modifications are acknowledged. The rationale of curing incontinence by restoring normal anatomy in the course of identifying and repairing discrete fascial defects has led to increased acceptance and use of the paravaginal or obturator shelf repair. PMID- 1878512 TI - Urinary tract infections in women. AB - Factors influencing urinary tract infections depend on a balance between bacterial virulence (bacterial adhesion to tissues, hemolysin, and aerobactin) and on the host's defenses (local immunoglobulin production). Predisposing factors for the development of urinary tract infections in women are physiologic changes with aging, use of catheters, and genitourinary operations. Therapy for uncomplicated urinary tract infections usually consists of a single dose of medication for 3 to 7 days, although the 1-day regimen was proved to be quite effective. Treatment of complicated urinary tract infections is by intravenous medications. New drugs for treatment of urinary tract infections are also reviewed. PMID- 1878513 TI - Pathology of the fallopian tube. AB - Tubal carcinoma and serous adenocarcinoma of the ovary are remarkably similar in biologic characteristics and tumor markers, which suggests that the management for tubal carcinoma would be based on that for ovarian carcinoma. The cases with rare histologic features, including endometrioid carcinoma, mixed mullerian tumor, and malignant fibrous histiocytoma have been reported. In the genesis of tubal pregnancy, microscopic evidence of silent inflammation has attracted special interest recently. With the development of sophisticated diagnostic tests and the progress of medical management, it has become possible to treat unruptured tubal pregnancies by pharmacologic approaches, laparoscopy, or transvaginal sonographic control. This review briefly outlines the conspicuous pathologic and etiologic features of neoplasms, ectopic pregnancy, and abnormality of the fallopian tube, and discusses some recent observations regarding these disorders. PMID- 1878514 TI - Pathology of the ovary. AB - Recent medical articles on pathology of the ovary have contributed to a better understanding of ovarian cancer. Postmenopausal women with ovarian neoplasms, especially bilateral ones, are at great risk that they are malignant. Methods for histologic and frozen-section sampling of ovarian neoplasms may vary from one pathology laboratory to another. Primary peritoneal cancer is a distinct clinical entity and all physicians operating on women with pelvic cancers should be alert for its presence. Serum CA 125 analysis may be of value in determining whether to carry out a second-look operation in women with epithelial ovarian cancer. The influence of rupture of the capsule of epithelial ovarian tumors, hydronephrosis, and disease limited to the ovaries and survival are discussed. PMID- 1878515 TI - Benign breast disease. AB - Perhaps the most remarkable trend relevant to benign breast disease during the past year is the relative paucity of new investigations. This interesting trend is reflected in one of the most remarkable recent texts on this subject. In The Breast: Comprehensive Management of Benign and Malignant Disorders (Bland et al., eds. WB Saunders, 1991), only 70 of 1100 pages are devoted to benign breast disease. The majority of recent reports have focused on three issues: symptomatic treatment of breast pain, expectant management of clinically benign masses in younger women, and cytologic differentiation of benign and precancerous cystic lesions. PMID- 1878517 TI - Family planning. PMID- 1878516 TI - New developments in breast cancer research. AB - The last few years have shown an extraordinary development of laboratory and clinical research in breast cancer. The areas which appear particularly important for possible clinical application are many and diversified. In this review we will update the present knowledge regarding four major issues: 1) biologic and molecular tests of prognostic significance in operable breast cancer patients; 2) detection of breast cancer cells in the bone marrow; 3) the endocrine aspects of breast cancer treatment; and 4) the indication of conservative treatments. PMID- 1878518 TI - Gynecologic urology. PMID- 1878519 TI - Gynecologic pathology. PMID- 1878520 TI - Audit of diagnostic accuracy of FNA cytology specimens taken by the histopathologist in a symptomatic breast clinic. AB - One thousand and two patients with palpable breast lumps have had fine needle aspiration at a surgical symptomatic breast clinic where the pathologist takes, stains and immediately reports the aspiration cytology smears. High levels of complete sensitivity (95.7%) and specificity (100%) have been maintained with a combined complete sensitivity for aspiration cytodiagnosis, mammography and clinical assessment of 99.7%. Significant reductions of unnecessary biopsies and out-patient revisits have allowed major resource savings to be made. In view of the high degree of accuracy obtained by this approach to the investigation of palpable breast lesions, combined clinics with their benefits for the patient, both physical and psychological, should be encouraged. PMID- 1878521 TI - Evaluation of the cost effectiveness of establishing a fine needle aspiration cytology clinic in a hospital out-patient department. AB - In an attempt to reduce the number of inadequate smears processed by our laboratory and the false negative rate of fine needle aspiration cytodiagnosis, we have introduced a fine needle aspiration cytology service where aspirates are taken by the cytopathologist in a clinic. In the 12 month period since the introduction of this service, the number of inadequate smears fell sharply. Nine per cent of the specimens were inadequate compared with 43% of specimens from other sources. The establishment of the clinic resulted in a threefold reduction in the cost of diagnosing breast lesions. PMID- 1878522 TI - Comparative ploidy studies using cytological and paraffin section preparations. AB - The ploidy profiles of benign and malignant tumours can be obtained using image analysis. However, the results of ploidy studies have varied according to the type of specimen used. We compared the ploidy profiles of paraffin embedded thin sections, cytospin preparations of disaggregated cells, and cytological smears from the same specimen as defined by image analysis. Ten benign breast lesions, 10 breast carcinomas and 10 malignant melanomas were investigated in this way. Preparations stained by the Feulgen technique were examined using the MD20 video image analysis densitometry system. Ploidy profiles were obtained by measuring the integrated optical density of at least 200 nuclei. By paying proper attention to the quality of fixation and presence or absence of cytoplasm around cells, comparable results were found for all preparations in each case. We therefore conclude that if careful attention is paid to the technical quality of the material, reliable ploidy results can be obtained by image analysis. PMID- 1878523 TI - Does microhistology improve the cytological diagnosis of liver and pancreatic tumours? AB - Guided percutaneous fine needle aspiration cytodiagnosis of the liver, retroperitoneum and pancreas was performed in 197 patients. In 42 cases, material left after the smears were prepared was embedded in paraffin wax for histological examination. Six liver tumours and seven pancreatic tumours were identified in this material. In two cases the diagnosis of liver cell carcinoma was made only after microhistological examination. Re-examination of the cytological material in both cases disclosed features of liver cell carcinoma which were underestimated in the first examination and diagnosed only broadly as cancer cells. On the other hand, in another case cancer cells were present only in the smear and absent in the microhistological preparation. Diagnosis of pancreatic tumours was generally not improved by microhistological examination. In one case cancer cells were present only in the cytological material. In another case a cytological diagnosis of suspected cancer was confirmed as adenocarcinoma by microhistology. The diagnosis of non-neoplastic material in the remaining 29 cases were identical by cytopathology and microhistology. It is concluded that the microhistology of needle aspirate material complements cytological examination and can refine diagnosis although it increases cost. PMID- 1878524 TI - The significance of nuclear grooves and phagocytosis in the diagnosis of metastatic papillary carcinoma of the thyroid. AB - A 57-year-old patient presented with a lesion of the iliac bone. Cytological smears prepared from material aspirated from the lesion revealed cells with longitudinal nuclear grooves and haemosiderin within their cytoplasm. These observations led to a diagnosis of metastatic thyroid papillary carcinoma which was confirmed by histological examination. PMID- 1878526 TI - Terminology: fine needle aspiration cytology and biopsy. PMID- 1878525 TI - Metastatic renal clear cell carcinoma in the thyroid gland diagnosed by fine needle aspiration cytology. AB - An 81-year-old woman presented with a mass in the right lobe of the thyroid. Fine needle aspiration of this lesion showed metastatic clear cell carcinoma. This was subsequently confirmed histologically. In patients with metastatic carcinoma, tumour deposits are frequently found in the thyroid. The most common metastatic tumour to masquerade as a primary thyroid tumour is a renal cell carcinoma. In patients with this tumour the possibility that a thyroid mass may be a metastatic deposit should always be considered. PMID- 1878527 TI - Carcinoid tumour of breast diagnosed by FNA. PMID- 1878528 TI - Fine needle aspiration cytodiagnosis as a pre-requisite for primary medical treatment of breast cancer. AB - The accurate non-surgical diagnosis of breast lumps allows assessment of breast cancer patients for conservation or neoadjuvant primary treatment before surgical intervention. We have analysed the accuracy of clinical assessment, fine needle aspiration cytology (FNAC), and mammography in over 868 women seen in a symptomatic breast clinic. Clinical examination by an experienced breast physician, together with FNAC, detected over 99% of the cancers with a 12% false positive rate. A cytological diagnosis of definite carcinoma was obtained in 69% of women with breast cancer with no false positive result from the women with benign conditions producing a 100% positive predictive value. These results indicate that it would be acceptable to give pre-surgical systemic endocrine or chemotherapy to women with positive cytology which is therefore a prerequisite for a neoadjuvant therapy programme. PMID- 1878529 TI - Stability of diltiazem in different biological fluids. AB - The hydrolysis of diltiazem in biological fluids: whole blood, plasma, and gastric fluid was investigated under conditions considered close to the physiological situation. The most significant rate of hydrolytic degradation was found in whole blood (half-life of 27 h), followed by plasma (half-life of 88 h), while the least significant degradation rate was observed in gastric fluid (half life 153 h). The kinetic profiles of diltiazem hydrolysis indicate that hydrolytic degradation in the biological fluids makes a minimal contribution to the clearance and disposition of the drug. PMID- 1878530 TI - A method for calculating the mean residence times of catenary metabolites. AB - A method for calculating the mean residence times of metabolites in the body, systemic circulation, and peripheral tissue is described. The calculations require the AUC, AUMC, and derivatives of the plasma concentration versus time curves of the metabolite and its precursor. The method is applicable to metabolites with any precursor order and does not require separate administration of the metabolite. The approach is applied to published data for the primary and secondary metabolites of ketamine. PMID- 1878531 TI - Endogenous plasma N-acetylcysteine and single dose oral bioavailability from two different formulations as determined by a new analytical method. AB - A method to quantitate N-acetylcysteine in plasma using reductive cleavage with tributylphosphine and post-HPLC column derivatisation with omicron-phthalaldehyde is described. Using this method, endogenous average concentrations of 0.08 microM were measured in 10 volunteers participating in a crossover study to compare the bioavailability of two different formulations of N-acetylcysteine. The drug was detected in plasma for up to 12 h after administration of a single oral dose (200 mg); the Cmax values were up to 20 times the endogenous levels. The sensitivity and selectivity of the method should thus enable the behaviour of N acetylcysteine after oral administration to be properly described and bioavailability studies to be performed. PMID- 1878532 TI - Kinetics of acetaminophen after single- and multiple-dose oral administration as a gradient matrix system to healthy male subjects. AB - The in vivo characteristics of two formulations of a recently developed controlled-release system, the Gradient Matrix System (GMS-1 and GMS-2), with acetaminophen as a model drug compound have been determined in healthy volunteers both after separate single- and multiple-dose administration. Values for the mean residence time (MRT) were increased from 5.2 h for an oral solution to 10.2 and 13.3 h for two GMS formulations after single dosing. Peak plasma concentrations were lower for the two GMS formulations after single dosing compared to the oral solution. The bioavailability, relative to the oral solution, was 91 per cent and 84 per cent for the two GMS formulations tested. After multiple dosing of one of the GMS formulations over 5 days, no change in AUC compared to the single dose AUC occurred. Steady state was reached within 2-3 days of twice daily dosing of the GMS formulation. The peak-trough-fluctuation (per cent PTF) was 44 per cent. No signs of dose dumping were observed in fasted subjects. A plateau-like plasma drug concentration profile at steady state was maintained with the GMS formulation. PMID- 1878533 TI - Comparison of in vitro and in vivo release characteristics of acetaminophen from gradient matrix systems. AB - An effort was made to correlate the in vivo and in vitro release data of acetaminophen from two formulations of a recently developed controlled-release system, the Gradient Matrix System (GMS-1 and GMS-2). The in vivo release curves, obtained by deconvolution of the plasma concentration time plots, showed a small inter-subject variability. GMS-1 with fastest in vitro release also showed fastest in vivo release. A good relationship was only found after time-scaling of the release data. PMID- 1878534 TI - Disposition and pharmacodynamics of dichloroacetate (DCA) and oxalate following oral DCA doses. AB - Healthy volunteers received intravenous and/or oral doses of sodium dichloroacetate (DCA) in various single and multiple dose regimens. A crossover bioavailability study proved abortive because second and subsequent doses showed significantly longer terminal elimination half-lives (means 3.64 h and 9.9 h, respectively) than was the case for initial doses (1.58 h). A parallel bioavailability comparison failed to show that oral doses were significantly different from 100 per cent bioavailability (AUCoral, 604 micrograms h-1 ml-1; AUCi.v., 489 micrograms h-1 ml-1). The time required to elapse between individual doses, in order to prevent second doses having relatively long half-life values, varied in different individuals from 1 week to greater than 3 months. No cardiac or central nervous system effects were recorded by echocardiography and digit symbol substitution tests, respectively. The mean renal clearance of DCA was 42.9 ml h-1. No differences were observed in DCA kinetics between male and female subjects. PMID- 1878535 TI - Bioavailability of diltiazem as a function of the administered dose. AB - Diltiazem undergoes extensive first-pass metabolism; extrapolation from single to repeated administration thus underestimates plasma concentration values. In order to validate the hypothesis of a partially saturable first-pass effect, four single doses of diltiazem (10, 20, 40, and 120 mg) were administered at weekly intervals to eight healthy volunteers. Results showed that: (a) the inter-subject variability was highest at the lowest dose at the highest dose; (b) bioavailability was almost nil in 3 of 8 of the subjects after the administration of the 10 mg dose; (c) the mean bioavailability increased with the dose from 11.8 +/- 2.5 per cent after 10 mg to 28.2 per cent after 120 mg; (d) the elimination half-life was dose-related; (e) the renal excretion of diltiazem increased with the administered dose from 1.0 +/- 0.3 per cent after 10 mg to 3.0 +/- 0.5 per cent after 120 mg; (f) the greatest amounts of circulating metabolites were present after the lowest doses. These results are consistent with a partially saturable first-pass effect for diltiazem. PMID- 1878536 TI - [The value of NMR tomography in the planning of HDR-afterloading brachytherapy in cervical carcinomas. The experiences with 41 patients]. AB - In 41 patients with inoperable cervical carcinomas, afterloading brachytherapy was used in combination with radiotherapy after planning with MRI (1.5 T spin echo multislice technique). In 27 women, phantoms neutral to MRI were introduced into the uterus to create a topographic situation comparable to that during brachytherapy; at the same time, the position of the applicators was marked. Under the circumstances, MRI demonstrated the position of the uterus and the tumour, the vagina, the bladder, the rectosigmoid and the applicator phantoms in every case. In 88% it was possible to demonstrate the margin of the tumour and normal myometrium. In 18% of the patients, the technique lead to a significant and, in a further 30%, to a marginal improvement in brachytherapy technique. PMID- 1878537 TI - [The diagnosis of bladder carcinomas by NMR tomography: an improvement with Gd DTPA?]. AB - 85 patients suffering from urinary bladder carcinoma were examined by magnetic resonance imaging in a prospective study. Following precontrast diagnosis, 15 patients were given an intravesicular application of gadolinium-DTPA (Gd-DTPA). Another 35 patients received an intravenous bolus of GD-DTPA. A diagnostic advantage was achieved in only 2 of 15 tumours by using intravesicular contrast application. Compared to the precontrast diagnosis, a 14% improvement from 69% (precontrast) to 83% (contrast medium) was seen with Gd-DTPA applied intravenously in the diagnosis of the tumour stage. The diagnostic gain lies in the improved tumour recognition, the improved demarcation of papillary, non muscle-infiltrating tumours and in the more definite diagnosis of infiltration into neighbouring organs and the pelvic wall. Demarcation of perivesicular fatty infiltration is rendered more difficult by Gd-DTPA. PMID- 1878538 TI - [The current status of the diagnosis and therapy of nonocclusive intestinal ischemia (NII)]. AB - Nonocclusive gut ischaemia is a disease of advanced age. Its causes are reduced cardiac output or shock, facilitated by digitalis, adrenaline, ergotamine and diuretics. The persisting microcirculation and development of gut necrosis leads to an increase in certain serum enzymes, such as lactate, LDH and CK-NB. The early application of mesenteric angiography using a DSA technique reveals four grades of underperfusion. Early and correct diagnosis of the disease should lead to intra-arterial treatment with prostaglandin. In ten out of 42 cases, conservative therapy led to reperfusion of the gut. PMID- 1878539 TI - [Transhepatic balloon dilatation of the ductus choledochus and the removal of choledochal calculi]. AB - In eight patients with stones in the bile duct, the concretions were removed percutaneously; in six, they were pushed into the duodenum following dilatation of the papilla and in two patients they were removed percutaneously by a transhepatic route using a Dormier basket. In two patients a stenosis at a choledocho-jejunostomy was successfully dilated by a percutaneously introduced balloon catheter. In five patients stenoses due to tumours of the bile duct were dilated percutaneously and an endoprosthesis introduced. There were no serious complications. The percutaneous transhepatic approach for the treatment of bile duct stones and of malignant obstruction is a valuable alternative to endoscopic and surgical treatment. PMID- 1878540 TI - [MR tomography of the liver at 1.5 tesla. The value of T1-weighted imaging with a fast multislice gradient-echo sequence during respiratory standstill]. AB - The diagnostic value of a fast multislice gradient-echo sequence was compared with that of conventional spin-echo sequences in a prospective study of 76 patients. With the multislice gradient-echo sequence, the entire liver can be examined in less than 3 minutes since five sections can be imaged during one breath-holding period. The strongly T1-weighted gradient-echo sequence (GRE 100/5/80 degrees) yields a significantly better T1-contrast than the T1-weighted spin-echo sequence (SE 500/15) (p less than 0.01) and thus improves the visualization of liver lesions. Another major advantage of the fast gradient-echo sequence is the pronounced reduction of motion artefacts. PMID- 1878541 TI - [The optimization of chondromalacia patellae diagnosis by NMR tomography. The use of an apparatus for cartilage compression]. AB - The aim of this study was to improve the MRI diagnosis of CMP, with special reference to the early stages and accurate staging. For this purpose, the retropatellar cartilage was examined by MRI while compression was carried out, using 21 patients and five normal controls. The compression was applied by means of a specially constructed device. Changes in cartilage thickness and signal intensity were evaluated quantitatively during FLASH and FISP sequences. In all patients the results of arthroscopies were available and in 12 patients, cartilage biopsies had been obtained. CMP stage I could be distinguished from normal cartilage by reduction in cartilage thickness and signal increase from the oedematous cartilage during compression. In CMP stages II/III, abnormal protein deposition of collagen type I could be demonstrated by its compressibility. In stages III and IV, the method does not add any significant additional information. PMID- 1878542 TI - [The estimation of the effective dose in bone mineral measurements with photon absorptiometry and computed tomography]. AB - There is still some uncertainty in the assessment and comparison of patient dose which results from bone mineral measurements on the lumbar spine by photon absorptiometry and x-ray computed tomography (CT). In the literature, skin dose values are offered in almost all cases. These are not meaningful, however, as the size of the irradiated volume and the radiation sensitivities of the respective organs are not taken into account. Here, the concept of effective dose has to be applied. An assessment of effective dose resulted in approximately 1 mu Sv for absorptiometry and approximately 30 mu Sv for computed tomography with low kV and mAs values. For lateral lumbar spine films which are often taken in connection with absorptiometry, at least 700 mu Sv have to be added. In CT, additional 30 mu Sv result from the lateral topogram which is required for positioning. The concept of effective dose, the data and assumptions used in its assessment and a comparison to other risk factors, as for example natural background radiation of approximately 2400 mu Sv per year, are discussed in detail. PMID- 1878543 TI - [The comparative measurement of the bone marrow dose in quantitative computed tomography (QCT), dual-photon radiography (DPX) and conventional x-rays of the LS]. AB - One of the issues in the discussion on the best method for measuring the bone mineral content is the relevance of the applied dose. We used highly sensitive thermoluminescent dosimeters (TLD) to directly compare bone marrow doses in a human phantom. DPX gave a bone marrow dose in the lumbar spine of 4 mu Gy, in QCT the dose corrected to the same amount of irradiated marrow was about 1 mGy. This value is in the same range as conventional a.p. plus lateral view x-rays of the lumbar spine. Corrected to the total body dose, the QCT dose is as low as 10% of the yearly background irradiation. It should therefore be radiobiologically irrelevant. PMID- 1878544 TI - [The diagnostic accuracy of MRT in cruciate ligament injuries]. AB - Lesions of the anterior cruciate ligaments may be demonstrated by MRI with an accuracy of 99%. Standardised technique with sagittal and coronal projections produces excellent results. Localisation of the site of rupture can be achieved in 95% of cases. MRI provides a valuable method for diagnosing lesions of the cruciate ligaments. PMID- 1878545 TI - [The x-ray morphology of parosteal osteosarcoma (POS)]. AB - 31 cases of parosteal osteosarcoma (POS) including both the differentiated and dedifferentiated variant were reviewed. Most patients were in the second and third decades of life. The tumours usually arose in the meta-diaphyseal (52%) and diaphyseal (33%) portion of long bones with a predilection for the knee (55%). Twenty-seven percent of patients showed involvement of the medullary cavity. 68% of lesions affected the bone cortex. A periosteal reaction was observed in 24% of patients. The characteristic but not pathognomic sign of a fine radiolucent line separating the tumour from the cortex was seen in only 48%. No characteristic radiographic features were evident that allowed a differentiation between the differentiated and the dedifferentiated POS. The presence or absence of medullary involvement was no a reliable diagnostic criterion. In all dedifferentiated POS, however, we observed a periosteal reaction. PMID- 1878546 TI - [A 3-dimensional reconstructive procedure in lumbar computed tomography]. AB - In this study, 50 patients were examined by a Siemens' "Somatom Plus"; continuous 2 mm sections between the third lumbar and first sacral vertebra were obtained. The accuracy of the 3-D reconstruction software programme was checked by measuring a polyethylene phantom of a second lumbar vertebra. Reconstruction was carried out with a threshold definition of 150 Hu. In each case, four standard projections and medio-sagittal, medio-lateral and coronary sections were reconstructed, photographed and compared with axial CT sections and conventional radiographs. All these imaging procedures were suitable for the diagnosis of osteochondrosis and chondrosis. Spondylosis was diagnosed more frequently on 3-D CT. Spondylarthrosis, with narrowing of the intervertebral foramina and root canals is shown particularly well by 3-D CT, since the entire extent of these structures can be seen. 3-D surface reconstruction of the lumbar spine is useful in the diagnosis of lumbar spondylarthrosis with narrowing of the root canals and of the spinal canal. This method of axial Ct is superior to conventional radiography of the lumbar spine in the usual two planes. PMID- 1878547 TI - [A rare location of aseptic bone necrosis]. PMID- 1878548 TI - [Acute calcifying tendinitis of the musculus longus colli]. PMID- 1878549 TI - [A combination of multiple cerebral aneurysms, fibromuscular dysplasia and multiple spinal hemangioblastomas. A random or a dysontogenetically explicable coincidence?]. PMID- 1878550 TI - [Variability and reproducibility in the determination of left-ventricular heart volume by cine-MR. A comparison of measurement methods]. AB - Sixteen normal individuals were examined on a 1.5 T instrument using gradient echo sequences (cine-MR). The results of various computations were tested with respect to agreement and reproducibility of the methods. The ejection fractions calculated from bi-plane and 3-dimensional reconstructed volumes showed very low standard deviations of mean values (SD less than 2%). Volumes calculated from a single plane produced the greatest scatter of mean values (SC approximately 5%). In all sixteen subjects, the MR findings showed good reproducibility. There was very little inter-observer variability (variability less than 5%). A comparison of various methods showed that bi-plane and monoplane volume calculations obtained by MR in the cardiac axis are more accurate than those obtained by echocardiography (MR:R greater than 0.75, p less than 0.001; echo:R less than 0.75, p greater than 0.05). PMID- 1878551 TI - [Arrhythmogenic effect of acoustic cavitation in isolated rat heart perfused with physiological solution]. AB - In experiments on isolated rat hearts the effects of focused continuous and impulse ultrasound (543 Hz, with intensity up to 7.8 W/cm2 at a focal region) on a pressure developed by left ventricle and electrograms were studied. In all experiments ultrasound induced extra-excitations of the heart, which appeared when intensity was 1.35 +/- 0.21 W/cm2 (n = 9). Simultaneously with the extra excitations the cavitation bursts were recorded at intensity of 1.52 +/- 0.18 W/cm2 (n = 6). Acoustic cavitation (after 30 sec of exposure) resulted in a significant decrease of the developed pressure (from 100.8 +/- 3.8 mm Hg to 95.1 +/- 4.3 mm Hg, p 0.001), measured in 2 min after the end of the exposure. In the absence of cavitation the ultrasound was found to have no effects on cardiac performance. Electrograms recorded during acoustic pacing show that a pattern of the heart excitation changed from stimulus to stimulus. PMID- 1878552 TI - [Synchronization effects in the pacemaker during high-frequency atrial stimulation]. AB - The succession of intra-impulse intervals in venous sinus of isolated frog heart was studied during suprathreshold atrial stimulation at a frequency exceeding the initial pacemaker rate by l5-200%. Near to the initial and multiple frequency pacemaker synchronization takes place with the stimulator rhythm. With the stimulation of frequency increase atrial impulses begin to conduct retrogradely and regular ectopic rhythm is established. A unilateral pacemaker acceleration with the unilateral frequency drawing together is revealed in intermediate areas. Different effects appear to accompany it including asymptotic and cyclic synchronization proving in the form of arrhythmias. PMID- 1878553 TI - [Effects of dephosphorylated core of 2',5'-oligoadenylate (2',5'-ApApA) on the electric activity of snail neurons]. AB - On nervous ganglion of snail Helix pomatia was shown the effect of dephosphorylated core of 2',5'-oligoadenylate (2',5'-ApApA) on pacemaker electrical activity of RPa2 snail neurons. In experiments, solution of 2',5' ApApA in concentration 5 x 10(-5) mol/l effected snail nervous ganglion in the course of 2 min then it was washed in the course of 2 hours. PMID- 1878554 TI - [Postsynaptic potentiation of end plate currents in the rat diaphragm at different levels of synaptic acetylcholinesterase activity]. AB - Nerve-evoked end-plate currents were recorded intracellularly in rat diaphragm when acetylcholinesterase (AChE) was intact or in the presence of galanthamine which reduces AChE activity up to 50% or 75%. Coefficient of correlation of the dependence between half-decay time and amplitude of end-plate currents during short tetanic stimulation pulse (20, 50 and 100 impulses per second) of motor nerve and the slope of this dependence were used to estimate the postsynaptic potentiation. Our results indicate that postsynaptic potentiation shows up clearly when AChE is fully active and grows significantly when AChE activity is slightly reduced. It is proposed that the modulation of the synaptic transmission can be performed by means of postsynaptic potentiation and synaptic AChE can take part in such way of modulation when varying its own activity under the influence of any endogenous factors. PMID- 1878555 TI - [Adaptation of the body to the effects of stress increases the resistance of cardiac nuclei to damaging effects of single-chain exogenous DNA]. AB - The effect of adaptation to stress exposure on the resistance of nuclear DNA to damaging effect of one-chain exogenous DNA was investigated by flow cytometric fluorescence method. It was shown that after the administration of one-chain DNA in concentration of 50 micrograms/ml into the nuclei suspension almost half of nuclear DNA was damaged in control. In adaptation this phenomenon was 5.5 times less pronounced. When the one-chain DNA concentration was increased, this protective effect of adaptation remained. The possible mechanism of the DNA protective effect of adaptation is under consideration. PMID- 1878556 TI - [Functional activity of the venous system in the development of hypertension in rats]. PMID- 1878557 TI - [Post-resuscitation toxemia and possibilities of its correction by albosorb]. AB - Albumin with enhanced sorption capacity (albosorb) was infused in animals after 10 min long clinical death caused by blood loss to correct endogenic intoxication. The albosorb infusion enhanced the blood plasma astringency both with respect to hydrophobic and hydrophilic molecules. PMID- 1878558 TI - [Study of eye proteoglycans by means of infrared spectroscopy]. AB - The infrared spectra of standard hyaluronic acid, proteochondroitin sulfate, aggregates of proteoglycans and spectra of the vitreous body, cornea and sclera were obtained in the region of 4000-400 cm-1. The comparative analysis of the spectra of these tissues and spectra made it possible to identify greater absorption bands of these biopolymers. PMID- 1878559 TI - [Mechanism of antioxidant action of carnosine]. AB - The comparative study of the antiradical activity of carnosine and vitamin C was carried out by the means of the evaluation of quenching of ESR signals of 2,2 diphenyl-1-picrylhydrazyl (DFPH) and semiquinone radical of alpha-tocopherol. It was shown that carnosine is not able to quench the ESR signals of the stable radical of DFPH and semiquinone radical of alpha-tocopherol. It permits to conclude that: a) carnosine does not interact directly with highly active free radicals; b) carnosine is unable to regenerate the radical of alpha-tocopherol to form the antiradical synergistic couple. The data obtained are consistent with the idea that there is a difference between on the antioxidant mechanism action of vitamin C and carnosine due to the difference in the antiradical activity of these compounds. PMID- 1878560 TI - [Platelet activating factor inhibits irritant-induced leukocyte migration into mouse peritoneal cavity]. AB - The effect of platelet-activating factor (PAF) on the leucocytes accumulation into mouse peritoneal cavity, that induced by high-molecular irritants carrageenan and polyacrylic acid pentaerytritol (carbopol) was studied. It was found that injection of PAF into peritoneal cavity one hour before i.p. injection of the irritants did not change their effects. On the contrary the injection of PAF simultaneously with the irritants or 3 and 6 hours after these injections inhibited the leucocyte accumulation into the peritoneal cavity and/or these injections increased the leucocyte adhesion to the peritoneal covering. It was supposed that finding effects are mediated by the change of leucocytes adhesion under action of PAF. PMID- 1878561 TI - [Effects of high-density lipoproteins on thrombin-induced platelet aggregation]. AB - Using new-developed method of aggregates radius measurement in suppression of washed human platelets, it has been shown, that HDL, in concentration of 190 ug/ml and in higher ones, totally inhibited aggregation, induced by 0.075 U/ml thrombin. For the same effect on aggregation, induced by 0.225 U/ml thrombin, HDL in concentration of 1320 ug/ml were needed. PMID- 1878562 TI - [Effects of lipid peroxidation stimulation and inhibition on myoglobin and creatine kinase kinetics in uncomplicated and complicated forms of myocardial infarct]. PMID- 1878563 TI - [Neutrophil motility in patients with early infection (rapid analysis using automatic image processing system, Magiscan)]. AB - The authors studied the dependence of blood neutrophil motility on the physical state of patients with infected wounds. Neutrophil motility was recorded and analyzed with the help of Magiscan-2a system of automatic image processing. A special software was developed for monitoring the movement of cells and measuring their displacements. Motility of each separate cell and a mean motility of the neutrophil population were determined on the glass in the microscope field (512 x 512 microns). Velocity of each neutrophil was shown to be nonuniform but approximately constant. Cell velocities in each probe were distributed in a continuous manner. Mean velocity of neutrophils in the probe was a stable index of the population motility. Decrease in neutrophil motility in the blood of patients with infected wounds was probably due to the adverse effect of serum factors. The application of the system of image processing makes it possible to carry out express analysis of neutrophil motility to estimate the efficiency of medical treatment. PMID- 1878564 TI - [Detection of nootropic activity indicated by acute inhibition of orientation reaction]. AB - Exploratory locomotor activity was studied in the experiments on adult male mice. It was shown that routine nootropic drugs as well as newly synthesized nootropic compounds were able to facilitate the development of inhibition during one registration session. Inhibition may be used for revealing only selective nootropic drugs devoid of sedative and stimulating effects. PMID- 1878565 TI - [Anti-ischemic action of a 1-hydroxy-2,2,6,6-tetramethylpiperidine derivative from a series of nitroxyl bioantioxidants]. AB - The experiments have been performed on 216 Wistar rats to examine anti-ischaemic action of the 1-hydroxy-2,2,6,6-tetramethyl-piperidine derivative (I), whose antioxidant properties were, earlier shown for model systems. Introduction of I (10(-4) M) into the perfusion medium and the subsequent storage (37 degrees C) of isolated liver was shown to decrease the accumulation of lipid peroxidation products (MDA). Compound I administrated (5 x 10(-6)-10(-5) M) in perfuse medium of isolated (Langendorff method) and ischemized (30 min, 37 degrees C) heart improves contractile function (Pmax) and decreases end-diastolic pressure at postischaemic period. In vivo injection of I increases (12 mg/kg, i.p.) the number of rats survival after sublethal time (2.5 h) of liver total ischaemia, increase (35 mg/kg, i.p.) the number of rats survival and improves parameters of heart function after ischaemic shock (6 h ischaemia and reperfusion of limbs). The analog of I, corresponding amine, possessing no antioxidant properties also fails to exhibit any anti-ischaemic effect. PMID- 1878566 TI - [Experimental assessment of the effectiveness of modified polyhemoglobin in the model of extreme hemodilution]. AB - The efficacy of the modified polyhemoglobin suggested as an artificial oxygen transporting substitute was estimated in the model of extreme hemodilution in dogs. It was shown that O2 consumption in dogs had been supported on the normal level during 4 hours after total exchange transfusion with the polyhemoglobin solution. Index of hemodynamics testifies that preparation has hemodynamics action. The conclusion was made that this modified polyhemoglobin has been effective O2 carrying blood substitute. PMID- 1878567 TI - [Study of antimutagenic properties of bio-ginseng in mammalian cells in vitro and in vivo]. AB - The impact was studied of bio-ginseng produced from ginseng callus cells on the rate of chromosome rearrangements in Chinese hamster cells and in continuous tumor cells of mice (Ehrlich strain). Bio-ginseng reduced rate of spontaneous SCE as well as the level of mitomycin C-induced chromosome aberrations in Chinese hamster cells. It protected ascitic tumor cells (Ehrlich strain) against the mutagen action of urea nitrosomethyl. PMID- 1878568 TI - [Immunosuppression induced by respiratory viruses (influenza virus, adenovirus) in mice]. AB - The influence of respiratory viruses (adenovirus, influenza virus) on humoral immune response to heterologous T-dependent and T-independent antigens was studied. It was shown that inoculation of mice by the influenza virus (A/PR8/34 A/PR/8) 3 days before sheep red blood cells administration led to the inhibition of antibody forming cell (AFC) and immunoglobulin, forming cell (IFC) increase on 69% and 59% respectively. Adenovirus type 6 induced the similar suppression of AFC and IFC formation. Thus, viruses induced immuno-suppression, which was polyclonal. It was also shown that virus of one strain (type) could inhibit immune response to another strain (type) of virus. The immune response to T independent antigen was not suppressed. The virus-induced immunosuppression was dependent on: 1) the infectivity of respiratory viruses, 2) the route of virus and heterologous antigen injection, and 3) the interval between the viruses and antigen inoculation. PMID- 1878569 TI - [Dynamics of local defensive reactions in the lungs in acute experimental inflammatory process induced by respiratory syncytial virus]. AB - Study has been made of broncho-associated lymphoid tissue (BALT), the number and functional activity of lung phagocytes, with 42 mice BALB/c, induced by respiratory-syncytial virus. With virus inflammation a decreased number of lung macrophages, their stronger attraction and increased lung chemotaxis have been observed. The addition of bacterial infection was accompanied by an increase in lung neutrophil, lymphocyte and macrophage, a decrease in lung neutrophil chemotaxis, an increase in macrophage phagocytosis and BALT hyperplasia. PMID- 1878570 TI - [Study of the action of tumor cell immunosuppressive factors on the production of cytokines by lymphocytes and macrophages and the mitogenic activity of interleukin-2]. AB - The effect of immunosuppressive factors (ISF) derived from tumor cell lines (mastocytoma P-815, leukosis EL-4 and melanoma B16) on the production of interleukin-1 (IL-1) by macrophages and of interleukin-2 (IL-2) by splenocytes of BALB/C mice was investigated. We could show that treatment of above cells by the tumor products resulted in strong decrease of IL-2 production but did not affect IL-1 secretion. ISF inhibited the proliferation of BALB/C lymphoblasts caused by recombinant IL-2. Thus, one of the significant mechanisms of ISF action seems to be disturbance of monolymphokine cascade of lymphocyte activation. PMID- 1878571 TI - [Increase in the quantity of highly repetitive sequences in extrachromosomal circular DNAs under inhibition of translation by cycloheximide]. AB - Small polydispersed circular DNA(spcDNA) was isolated from cultivated HeLa cells. Cells were treated by cycloheximide in concentrations of 1 and 50 micrograms/ml. Gradient fractions were dot blotted to nitrocellulose filters and were hybridized with different repetitive DNAs. The pool of repetitive DNA sequences in fraction of spcDNA increased for cycloheximide treated cells. The content of Alu sequences increased by 1.5-2.5 times, "classical" satellite DNA--by 5-7 times, alpha satellite--by 3-5 times. PMID- 1878572 TI - [Decrease of incidence of chromosome aberrations after a course of hyperbaric oxygenation]. AB - The influence of the course of hyperbaric oxygenation (HBO) on the peripheral blood lymphocytes chromosomes of 7 patients with different pathology and of 3 healthy volunteers was studied. It is proved that after HBO course the frequency of chromosome, aberrations of chromatid type hasn't been practically changed whereas the frequency of aberrations of chromosome type significantly decreases by three times on the whole. PMID- 1878573 TI - [Effects of strophanthin K and beta-acetyldigoxin in vitro on energy transformation of myocardial contractile protein system in toxic-allergic lesions of the cardiac muscle]. AB - Strophanthin K and beta-acetyldigoxin in vitro in concentration of 10(-6) M in TAM sharply increased the force generated by isolated myocardial contractile protein system (MCPS), and normalized the work performed by the system. This was accompanied by increase of ATP internal energy release (enthalpy) intensity, while a portion of energy, dissipating into heat did not increase proportionally. The mechanical efficiency of contractile process was normalized due to beta acetyldigoxin, and exceeded the normal level due to strophanthin K effect. Strophanthin K proved a positive effect on quantitative and qualitative economy of MCPS energy utilization, while beta-acetyldigoxin effected, on the whole, extensively. PMID- 1878574 TI - [Extrathymic localization of thymalin-containing cells in the epithelium of organs morphogenetically analogous to the thymus in prenatal human ontogenesis]. PMID- 1878575 TI - [Development of traumatic shock is accompanied by increased activity of polyspecific antibodies reacting with DNA and endotoxins]. PMID- 1878576 TI - [Seasonal changes in cardiovascular indices and monoamine content in the brain of rabbits]. AB - In our previous studies a rather substantial difference between the initial values of the cerebral blood flow was found. On the other hand the brain monoamine content varies in different months of the year when studied. Comparative analysis of these parameters in rabbit brain was the aim of this paper. The content of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in cortical and subcortical structures and the local cerebral blood flow (ICBF), the systemic arterial pressure (SAP) and pulse rate (PR) were studied. There were found seasonal variations in all parameters. A certain LCBF retardation in subcortical structures and cortex and the weakest effect of the stimulation was observed in May. There was a drop in SAP and some PR increase in the spring (April-May). Brain NA and 5-HT content showed seasonal changes with the lowest values near the winter months and reaching maximum in May as the PR does. Content of DA was low in May. So it seams possible that the ion ICBF in May can be explained by the decrease of brain DA at that time. The ICBF and the reactivity of cerebral microvessels seem to depend on the monoamine content and show seasonal variability. PMID- 1878577 TI - [Allotransplantation of cultured fibroblasts on non-healing wounds after autodermatoplasty]. AB - An allograft from man cultured fibroblasts has been received. Results of its transplantation on long not-healing donor wounds in 13 patients after autodermatoplastic operations have been studied. Expressed stimulating influence of cultured fibroblasts on donor wound epithelialization processes has been stated. In spite of allograft applications there has been no tearing away reactions. It has been connected with elimination of superficial cell antigens during cultivation. Microbe contamination of more than 10(2) is the contraindication for grafting. PMID- 1878578 TI - [Correlation between activity of tissue basophils and leukocytes and permeability of mesenteric venules of rats in experimental peritonitis]. AB - Calculation of adhered leukocytes, degranulated mast cells and leaked mesentery venules have been prepared in 1, 2, 4 and 8 hours after induction of inflammation. Number of adhered to the venular walls leukocytes enhanced with constant speed for the first 4 hours. The speed of the appearance of new mast cells with the signs of the degranulation in the period was raised. Alteration of the number (share) of leak vessels had parallel dynamic. This data show that in this model of inflammation the main role in disturbances of the permeability is played by products of the degranulation of must cells. In 4 hours and more predominant significance in genesis of disturbances of transport function of vessels wall begin to acquire metabolites of activated leukocytes--free radicals of the oxygen. Apparently this substances played an important role in the mechanism of releasing of the thrombosis. PMID- 1878579 TI - [Changes in interneuronal connections in the sensory-motor cortex of the offspring of moderately alcoholized female rats]. PMID- 1878580 TI - [Parameters of lens protein fluorescence quenching in early stages of hereditary cataract]. AB - Several physico-chemical parameters of lenses were investigated in IOR/Hab mice with hereditary cataract aged 4, 6, 8 weeks, i.e. at the stage preceding the development of cataract. The level of restored glutathione in the IOR/Hab lenses /2.0 mM/ was the lowest as compared to other lines but almost the same as in CBA/J /2.3 mM/. In the process of studying protein fluorescence quenching in cortex homogenates by nitrate anions a significant increase of the quenching constant was discovered in IOR/Hab mice: 10.4 M-1 in four-week animals and up to 32.3 M-1 in eight-week animals. The data obtained suggest that a progressing growth of the quenching constant in line IOR/Hab lenses is related to a decreased density of the protein negative charge resulted from their decreased phosphorylation. PMID- 1878581 TI - [Characteristics of morphological changes in ovary wounds after the use of steel and plastic scalpels]. AB - A comparative study of steel and plasma scalpel use in ovary operations is carried out in an experiment. 25 fertile female rabbits were operated on, in each one ovary was dissected by a steel scalpel, the other--by a plasma one. Sampling was performed on the 3-d, 7, 14, 21, 28-30-th day. At the relaparotomy of appendages operated on with the help of plasma scalpel, commissuring process was less prominent. Histological picture analysis has also shown plasma scalpel advantages--smaller tissue injuries, speeding up of wound healing process, drop in inflammatory reaction in response to influence. PMID- 1878582 TI - Does the breakpoint within the major breakpoint cluster region (M-bcr) influence the duration of the chronic phase in chronic myeloid leukemia? An analytical comparison of current literature. PMID- 1878583 TI - Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group. AB - Between April 1985 and March 1987 130 children and adolescents up to 18 years of age with first relapse of acute lymphoblastic leukemia (ALL) were registered on the stratified and randomized multicentric trial ALL-REZ BFM 85 designed for patients pretreated with intensive front-line therapies. Stratification criteria were time and site of relapse: bone marrow (BM) relapse on or up to 6 months after stopping front-line therapy (group A), BM relapse beyond 6 months after therapy (group B), and isolated extramedullary relapse at any time (group C). Treatment consisted of alternating courses of polychemotherapy including randomly administered high- or intermediate-dose methotrexate (HDMTX:12 g/m2 as 4-hour infusion; IDMTX: 1 g/m2 as 36-hour infusion). During maintenance therapy the patients received daily oral thioguanine and biweekly intravenous (IV) MTX. The overall second complete remission (CR) rate was 92% (groups A, B, and C: 88%, 92%, and 100%), and the probability of event-free survival (EFS) at 6 years is 0.31 +/- 0.04 (groups A, B, and C: 0.18 +/- 0.05, 0.30 +/- 0.07, and 0.72 +/- 0.11). HDMTX did not prove to be superior to IDMTX, which led to premature stopping of randomization. Risk factor analyses showed early relapse, particularly BM relapse within 18 months, and T-cell phenotype to be independent predictors of poor outcome. The incidence of central nervous system (CNS) relapses following BM relapse was 19%, indicating that reprophylaxis to the CNS with IV/intrathecal (IT) MTX was insufficient. For 17 children who received bone marrow transplantation in second CR from HLA-compatible siblings the EFS was 0.53 +/- 0.12 at 5 years. Their outcome was not influenced by the above-mentioned risk factors. With the proposed treatment regimen long-lasting second remissions can be achieved in about one third of patients even after intensive front-line treatment. PMID- 1878584 TI - Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma. AB - H65-RTA is an immunoconjugate that consists of the A chain of ricin (RTA), a ribosomal-inhibiting protein, coupled to a murine monoclonal antibody (H65) directed against the pan-T-cell antigen CD5. The CD5 antigen is heterogeneously expressed on cutaneous T-cell lymphoma tumor cells, but is not expressed on normal cells except lymphocytes. A phase I trial was therefore conducted in which 14 patients with cutaneous T-cell lymphoma progressive on other therapies were treated with up to three cycles of H65-RTA. The maximal tolerated dose (MTD) of H65-RTA was 0.33 mg/kg/d administered intravenously for 10 days as defined by dyspnea at rest at higher doses. Other reversible side effects included myalgia, mild hypoalbuminemia with weight gain, pedal edema, fatigue, fevers, and chills. Six patients received more than one cycle of H65-RTA without increased side effects compared with the first cycle. Pharmacokinetic analysis showed that peak serum drug levels were dose-dependent, and ranged from 1.13 to 5.56 micrograms/mL, with a terminal half-life ranging from 1.0 to 2.9 hours. The development of antibodies against the immunoconjugate was associated with a lower peak drug level, but not with enhanced side effects. Partial responses lasting from 3 to 8 months were documented in four patients. Three of the responding patients received more than one cycle of H65-RTA in the presence of anti immunoconjugate antibodies. The results from this phase I trial suggest that H65 RTA is an active drug in the treatment of cutaneous T-cell lymphoma. The immunoconjugate may be safely administered repeatedly, even in the presence of anti-immunoconjugate antibodies, with responses noted. Additional studies at the MTD are needed to define the response rate in this disease. PMID- 1878585 TI - Enzyme replacement therapy for Gaucher disease. AB - Four patients with moderately severe type I Gaucher disease were treated with commercially available mannose terminated glucocerebrosidase (Ceredase; Genzyme, Boston, MA) for up to 13 months. The enzyme was administered at the rate of three to four times weekly at one fourth the total recommended dosage, greatly decreasing the cost. Marked regression of hepatomegaly and improvement in liver function tests, peripheral blood counts, and serum angiotensin-converting enzyme levels were documented. The two patients with pulmonary involvement manifested improvement in pulmonary function tests. Skeletal disease remained unchanged. PMID- 1878587 TI - Phase I-II trial of pentoxifylline for the prevention of transplant-related toxicities following bone marrow transplantation. AB - Disease relapse and transplant related toxicities have limited the application of bone marrow transplantation (BMT) in the treatment for hematologic malignancies. Because elevated levels of tumor necrosis factor alpha (TNF-alpha) have been correlated with the development of transplant related complications, we conducted a phase I-II trial of pentoxifylline (PTX), a xanthine derivative capable of down regulating TNF-alpha production, in patients with hematologic malignancies undergoing BMT. Thirty consecutive adult patients (median age, 34) were entered and received either an allogeneic (n = 26) or autologous (n = 4) BMT. Patients were enrolled at increasing dose levels (1,200, 1,600, and 2,000 mg/d) from day 10 through day +100 posttransplant. PTX was well tolerated with no significant adverse side effects noted at any of the dose levels administered. The actuarial day 100 survival for these 30 patients was 90% (95% confidence interval 79% to 100%). When compared with a good risk control group, PTX recipients experienced less mucositis (3.7 +/- 1.1 v 18.7 +/- 1.1 days, P = .004), less hepatic venocclusive disease (10% v 65%, P = .001), a lower incidence of renal insufficiency (3% v 65%, P = .0003), required less days of total parenteral nutrition (TPN) (24.0 +/- 1.3 v 35.0 +/- 2.4, P = .001) and were discharged from the hospital earlier than controls (day 26.0 +/- 1.8 v 37.0 +/- 3.8, P = .01). In addition the incidence of graft-versus-host disease (GVHD) greater than or equal to grade II was also reduced among the PTX recipients (35% v 68%, P = .03). PTX at doses in excess of 1,200 mg/d further reduced the severity of mucositis, and TPN requirements resulting in earlier hospital discharge than patients receiving 1,200 mg/d of PTX. In this study oral administration of PTX in doses up to 2,000 mg/d was well tolerated and associated with a reduction in morbidity and mortality in patients undergoing BMT. Prospective randomized trials are currently in progress to test these preliminary observations. PMID- 1878586 TI - Recombinant human granulocyte-macrophage colony-stimulating factor after chemotherapy in patients with acute myeloid leukemia at higher age or after relapse. AB - To reduce critical neutropenia after chemotherapy (CT) for acute myeloid leukemia (AML) we administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients over the age of 65 years with newly diagnosed AML and to patients with early or second relapse. CT was 9-day 6-thioguanine, ara-C, and daunorubicin (TAD9) in newly diagnosed AML and sequential high-dose ara-C and mitoxantrone (S-HAM) for relapse. In patients whose bone marrow was free from blasts a continuous intravenous infusion of GM-CSF 250 micrograms/m2/d started on day 4 after CT. Thirty-six patients entered the study and 30 of them did receive GM-CSF. For comparison, a historical control group of 56 patients was used. Complete remission rate was 50% (18 of 36) versus 32% in controls (P = .09), and early death rate was 14% versus 39% (P = .009). Treatment with GM-CSF was not associated with major adverse events. Two patients showed a marked leukemic regrowth that was completely reversible in one patient and appeared to be GM-CSF independent in the other patient. Remission duration does not seem to be reduced after GM-CSF. Under GM-CSF the blood neutrophils recovered 6 and 9 days earlier in the TAD9 (P = .009) and S-HAM (P = .043) groups associated with a rapid clearance of infections in most patients. We conclude that GM-CSF was of therapeutic benefit to our patients and this provides a basis for larger controlled trials. PMID- 1878588 TI - Use of recombinant human interleukin-2 in conjunction with syngeneic bone marrow transplantation in mice as a model for control of minimal residual disease in malignant hematologic disorders. AB - Unlike allogeneic bone marrow transplantation (BMT), autologous BMT is not accompanied by immune-mediated graft-versus-leukemia (GVL) effects; hence, the relapse rate observed after autologous BMT in malignant hematologic disorders is higher than that observed after allogeneic BMT. Autologous BMT represents a much safer medical procedure available for many patients in need in situations where allogeneic BMT is not feasible or risky. The present experiments were designed to investigate whether it might be possible to combine the therapeutic benefits of autologous BMT with additional immunotherapy after BMT. The tumor model used for investigating GVL effects was the murine B-cell leukemia (BCL1), a spontaneous, nonimmunogenic, highly lethal leukemia of BALB/c origin. BALB/c mice inoculated with 10(3) BCL1 leukemia cells were treated on day-1 with cyclophosphamide 100 mg/kg and transplanted with normal syngeneic BM cells on day 0. High-dose recombinant interleukin-2 (rIL-2) (100,000 Cetus units x 3/day intraperitoneally x 5 consecutive days) was initiated on day +1, +7, or +21 after BMT. Kinetics of lymphocyte reconstitution after syngeneic BMT indicated a steep increase in the absolute number of peripheral blood lymphocytes on days 17 through 24. All experimental groups were observed for relapse. Mice receiving no rIL-2 therapy relapsed and died within 50 days after BMT, whereas mice receiving rIL-2 showed long-term disease-free survival. Optimal time for administration of rIL-2 was noted at 3 weeks post-BMT, with 90% of the mice surviving with no evidence of disease for more than 1 year. Similarly, when 10(4) BCL1 cells were given 1 day after syngeneic BMT to simulate minimal residual disease after syngeneic BMT, rIL 2 therapy administered at 14 days post-BMT seemed effective in prolonging disease free survival in contrast to the same regimen given at 1 day after BMT. Our data suggest that immunotherapy with rIL-2 should be further investigated as a new immunotherapeutic tool for decreasing the relapse rate after BMT for hematologic malignancies. PMID- 1878589 TI - Demonstration of osteonectin mRNA in megakaryocytes: the use of the polymerase chain reaction. AB - Platelets have been shown to release osteonectin on thrombin stimulation. The origin of platelet osteonectin was unclear as it may have been synthesized by megakaryocytes or it may have been endocytosed from plasma as other platelet alpha-granule constituents are. Platelet osteonectin has a larger apparent molecular size than the bone species, although the molecular basis for this difference has not been elucidated. These two issues have been addressed here by (1) examining the potential for osteonectin biosynthesis in human megakaryocytes by demonstrating the presence of osteonectin mRNA in purified megakaryocytes, and (2) comparing the coding portion of osteonectin transcript in megakaryocytes to the size of its bone counterpart. Because of the limitations of cell population purity and in obtaining sufficient numbers of megakaryocyte cells for Northern analysis, we have used the polymerase chain reaction (PCR) to detect the presence of human osteonectin mRNA in megakaryocyte and megakaryocyte-depleted bone marrow cells. Isolation of RNA, cDNA synthesis, and PCR were performed on human osteosarcoma SaOS-2 cells, enriched megakaryocytes, and megakaryocyte-depleted cells. Restriction enzyme analysis of PCR DNA products confirmed the identity of the products as those encoding osteonectin for all three cell populations studied. In addition, the sizes of DNA indicate that osteonectin genomic DNA, nuclear RNA, or altered transcript were not amplified, and that the transcript from megakaryocytes is the same size as that from bone cells. These data suggest that the difference in protein size between platelet and bone osteonectin is due to posttranslational modification. To overcome the possibility that megakaryocyte signal originated from contaminating cells (less than 5% by cell count), all three cell populations were diluted to less than one cell per tube and PCR amplification was performed. Limiting dilution analyses demonstrated the presence of osteonectin mRNA in single megakaryocytes as well as in single cells from the cell population depleted of megakaryocytes, suggesting the capacity for osteonectin biosynthesis in all cells studied. The procedure we describe in this report can be used to examine specific characteristics of mRNA molecules in heterogeneous cell populations and in situations where only small quantities of cells can be obtained. PMID- 1878590 TI - Granulocyte-macrophage colony-stimulating factor (GM-CSF) in human long-term bone marrow cultures: endogenous production in the adherent layer and effect of exogenous GM-CSF on granulomonopoiesis. AB - This study was designed to assess the presence of endogenous granulocyte macrophage colony-stimulating factor (GM-CSF) within adherent layers of human Dexter-type cultures and to investigate the effect on granulomonopoiesis of adding exogenous GM-CSF to the culture medium. The presence of GM-CSF was demonstrated using a bioassay, in which adherent layers from normal bone marrows gave rise to endogenous granulocyte-macrophage colony-forming units (CFU-GM) that were specifically inhibited by increasing amounts of an anti-GM-CSF neutralizing antibody. Using an immunoassay, the estimated amounts of GM-CSF were less than or equal to 40 pg per flask in adherent layers, while remaining undetectable in supernatants. The addition of 10 ng or purified recombinant GM-CSF per milliliter of culture medium increased slightly the CFU-GM output over a 5-week culture period. The addition of 50 ng/mL decreased significantly the CFU-GM output after 5 weeks of culture. This decrease was associated with major modifications of the adherent layer cell composition. Large round or ovoid macrophages were generated at the expense of the interdigitated and elongated stromal cells and the extracellular fibronectin network was no longer observed. These studies suggest that GM-CSF production by accessory cells (stromal cells and/or monocytes) is almost equal to its consumption by hematopoietic cells, a situation similar to that found in long-term cultures of murine marrows. They also show that the maintenance of granulomonopoiesis is decreased by adding more than 10 ng/mL of exogenous GM-CSF to the culture medium, which is related to the induction of adherent macrophages, the disappearance of the major smooth-muscle-like stromal cell component of the adherent layer, and that of the fibronectin extracellular matrix. PMID- 1878591 TI - Most primitive hematopoietic stem cells are stimulated to cycle rapidly after treatment with 5-fluorouracil. AB - To test whether primitive hematopoietic stem cells (PHSC) cycle rapidly during recovery from an initial 5-fluorouracil (5-FU) treatment, two doses of 5-FU were administered 1, 3, 5 or 8 days apart. Cells from treated marrow donors were mixed with untreated competitor marrow that would produce genetically distinguishable erythrocytes and lymphocytes, using hemoglobin (Hb) and glucosephosphate isomerase (GPI) transplantation markers. These cell mixtures were injected into lethally irradiated hosts. Functional abilities of donor marrow populations were assessed after 3, 6, and 12 months as percentages of donor type Hb and GPI in the host's circulating erythrocytes and lymphocytes, respectively. Bone marrow from mice treated with two doses of 5-FU 3 to 5 days apart was severely affected, producing circulating erythroid and lymphoid cells an average of only 25% of normal for doses 3 days apart, and 14% of normal for doses 5 days apart. Two doses of 5-FU administered 1 day or 8 days apart had much smaller effects, producing circulating cells 75% or 58% of normal. Thus, most PHSC are stimulated to proliferate rapidly 3 to 5 days after treatment with 5-FU, but far fewer PHSC proliferate as early as 1 day, or as late as 8 days, after the 5-FU treatment. PMID- 1878592 TI - Administration of erythropoietin to newborn rats results in diminished neutrophil production. AB - Very high concentrations of erythropoietin (epo), in clonogenic cultures, result in reduced production of neutrophils, and fetal progenitors are more sensitive to this effect of epo than are those of adults. However, the significance of this observation is unclear because no evidence of reduced neutrophil production has been presented following administration of recombinant epo to human or animal subjects. In the present study we injected newborn rats, beginning on the first day of life, with 20, 200, or 2,000 U epo/kg body weight, and measured serum epo concentrations after 2, 8, 24, or 48 hours. After selecting a dose that resulted in serum concentrations greater than 1,000 mU/mL (a concentration that resulted in down-modulation of neutrophil production from neonatal rat progenitors in vitro) other newborn rats were treated for 3 days with that dose (1,000 U epo/kg) or a vehicle control. Administration of epo resulted in increased hematocrits (P less than .001), reticulocyte counts (P less than .001), normoblasts/femur (P less than .05), and normoblasts/spleen (P less than .001). Recipients of epo also had more erythroid colony-forming units (CFU-E) (P less than .001) and higher CFU E tritiated thymidine suicide rates (P less than .01) than did controls. However, femurs and spleens of epo recipients contained fewer postmitotic neutrophils (femur, P less than .01; spleen, P less than .01), proliferative neutrophils (femur, P less than .01; spleen, P less than .02), granulocyte-macrophage colony forming units (CFU-GM) (P less than .005), and lower CFU-GM tritiated thymidine suicide rates (P less than .01). Seven and nine days after twice-daily administration of 2,000 U epo/kg, blood neutrophil concentrations had diminished (P less than .05). Thus, administration of high doses of recombinant epo to newborn rats resulted in diminished neutrophil production accompanying accelerated erythropoiesis. PMID- 1878593 TI - The role of interleukin-1 and granulocyte-macrophage colony-stimulating factor in the paracrine stimulation of an in vivo-derived murine myeloid leukemia. AB - WEHI-274.3 is a cell line isolated from an in vivo-derived, murine myelomonocytic leukemia. Although the survival and growth of WEHI-274.3 cells in vitro is absolutely dependent on the addition of exogenous growth factors such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or colony-stimulating factor-1, when injected into syngeneic mice the cell line is tumorigenic. Sera from normal mice contain low levels of an activity that sustains survival of WEHI-274.3 but does not stimulate growth. In contrast, sera from mice bearing the WEHI-274.3 leukemia contained levels of CSF-1 and GM-CSF that stimulated the growth of WEHI-274.3 cells. Supernatants of cultures of WEHI 274.3 cells contained an activity that stimulated 3T3 fibroblasts to release an activity that stimulated the growth of the WEHI-274.3 cells. The 3T3-stimulatory activity released by the WEHI-274.3 cells was neutralized completely with an antiserum specific for murine IL-1 alpha, but not with antiserum specific for IL 1 beta. Moreover, WEHI-274.3 cells both in vitro and in vivo contained high levels of IL-1 alpha and IL-1 beta mRNAs. The leukemia-stimulatory activity released by the 3T3 cells was neutralized by an antiserum specific for GM-CSF. We postulate that the IL-1 alpha constitutively released by the WEHI-274.3 cells stimulates the production of GM-CSF from host cells such as fibroblasts or endothelial cells. A similar paracrine mechanism of growth stimulation may occur in acute myeloid leukemias in humans. PMID- 1878594 TI - Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse. AB - To define the clinical and biologic significance of childhood acute mixed-lineage leukemia diagnosed by stringent criteria, we studied 25 cases of acute lymphoblastic leukemia expressing greater than or equal to 2 myeloid-associated antigens (My+ ALL), and 16 cases of acute myeloid leukemia expressing greater than or equal to 2 lymphoid associated antigens (Ly+ AML). These cases represented 6.1% of 410 newly diagnosed ALLs (two treatment protocols) and 16.8% of 95 AMLs (two protocols). T-lineage--associated antigens were identified in 9 of the My+ ALL cases and in 14 of those classified as Ly+ AML; all but 1 of the 19 cases that could be subclassified had an early thymocyte stage of differentiation. The My+ ALL cases had an increased frequency of French-American British (FAB) L2 morphology (36%); the Ly+ AML cases were characterized by FAB M1 or M2 morphology, low levels of myeloperoxidase reactivity and combined populations of myeloperoxidase-positive large blasts and small blasts generally of hand-mirror morphology. Karyotypic abnormalities included t(9;22)(q34;q11) in three cases of My+ ALL, 11q23 translocations in two cases of My+ ALL, and 14q32 translocations in three My+ ALL and five Ly+ AML cases. Mixed-lineage expression lacked prognostic significance in either ALL or AML; however, the findings indicate that some patients with Ly+ AML may respond to prednisone, vincristine, and L-asparaginase after failing on protocols for myeloid leukemia. At relapse, two My+ ALLs had converted to AML and two Ly+ AMLs to ALL; one case in each group showed complete replacement of the original karyotype. Acute mixed-lineage leukemia does not adequately describe the heterogeneity of the cases identified in this study and should be replaced by a set of more restrictive terms that indicate the unique biologic features of these leukemias. PMID- 1878595 TI - An inherited defect of neutrophil motility and microfilamentous cytoskeleton associated with abnormalities in 47-Kd and 89-Kd proteins. AB - A 2-month-old male Tongan infant presented with fever, severe skin and mucosal infections, hepatosplenomegaly, thrombocytopenia, and normal neutrophil counts. While polymorphonuclear neutrophil (PMN) morphology was normal, several neutrophil motile functions were found to be altered in the patient. Furthermore, two siblings had died in infancy with a similar clinical picture, raising the possibility of an inherited neutrophil defect. Random migration and chemotaxis, assessed by the under agarose method, were profoundly impaired. Actin polymerization, as measured by flow cytometry of N-(7-nitrobenz-2-oxa-1,3-diazol 4-yl)phallacidin (NBD-phallacidin)-stained PMNs, showed lower basal F-actin and a 1.75-fold increase in response to 10(-7) mol/L formyl-methionyl-leucyl phenylalanine (FMLP) compared with a 4.51-fold increase in control. Microscopic examination of NBD-phallacidin-stained PMN spread on glass showed decreased area of spreading and F-actin-rich filamentous projections distinct from control. The early phase of FMLP-induced right angle light scattering was absent, similar to the effect caused by cytochalasin-B (CB), an inhibitor of actin polymerization. Accordingly, FMLP induced secretion of elastase without the addition of CB. Staphylococcus aureus killing was 50% of control whereas superoxide production response to FMLP and surface expression of CD11b were greater than twice normal. Partial defects in actin polymerization and scatter were seen in the parents and release of elastase, in the absence of CB, was also increased in both parents. Sodium dodecyl sulfate-polyacrylamide electrophoresis of whole cell proteins from the patient showed a marked decrease in an 89-Kd protein (8% of control) and a marked increase in a 47-Kd protein (4.2-fold). Both mother and father had decreased 89-Kd (77% and 42% of control) and increased 47-Kd proteins (2- and 3.4 fold), although neither had recurrent infections or chemotactic defects. These studies describe a new inherited actin dysfunction syndrome associated with severe propensity to fungal infection and draw attention to the proteins of apparent molecular weights of 89 Kd and 47 Kd, which may be of great importance in the regulation of actin polymerization in human PMNs. PMID- 1878596 TI - Regulation of human fetal and adult globin genes in mouse erythroleukemia cells. AB - We have examined whether transfected mouse erythroleukaemia (MEL) cells can be used to examine differential expression of human gamma- and beta-globin genes. These cells, which express only their adult globin genes, will transcribe the human adult beta gene but not the fetal gamma genes when they are introduced on an intact human chromosome 11 by cell fusion. However, MEL cells stably transfected with the human A gamma gene attached to one of the active elements (HS2) of the beta-globin locus control region (LCR) readily produce gamma-globin mRNA in amounts equivalent to those seen with a comparable beta gene insert. When both beta and gamma genes are attached to HS2, equal amounts of beta A gamma mRNAs are produced, irrespective of the gene order. Furthermore, when HS2 is inserted into the 5' end of a 40-kb cosmid containing the G gamma A gamma-117 delta beta genes in their normal chromosomal organization (but with the Greek HPFH -117 A gamma gene mutation), it directs expression of readily detectable amounts of G gamma A gamma and beta-globin mRNAs in MEL cells. Therefore, under these circumstances we have observed no competition between beta and gamma genes for expression in MEL cells. These findings suggest that MEL cells are capable of perpetuating regulatory information involved in developmental control when it is provided by an intact chromosome, but are incapable of reconstructing such information on transfected DNA. PMID- 1878597 TI - Heterogeneity of the molecular basis of hereditary pyropoikilocytosis and hereditary elliptocytosis associated with increased levels of the spectrin alpha I/74-kilodalton tryptic peptide. AB - Hereditary pyropoikilocytosis (HPP) and hereditary elliptocytosis are closely related, congenital disorders of the red blood cell usually associated with defective spectrin self-association and abnormal limited tryptic digestion of the N-terminal of domain of spectrin. Enhanced cleavage by trypsin of spectrin from affected individuals at arginyl residue 45* and lysyl residue 48* frequently yields increased amounts of an alpha 1/74-Kd fragment at the expense of the normal alpha 1/80-Kd parent fragment. Limited tryptic digestion of three unrelated individuals with HPP showed the alpha 1/74 defect. To ascertain the molecular defect responsible for the abnormality, the structure of exon 2 of the alpha-spectrin gene was examined. Genomic DNA from the subjects was amplified by the polymerase chain reaction using primers flanking exon 2. Restriction endonuclease digestion of amplified products showed the loss of the HindIII site at codons 47 and 48 in one allele of subject 1 and abolished the AhaII site at codons 27 and 28 in one allele of subjects 2 and 3. Nucleotide sequence analysis of subcloned amplified DNA from the HPP subjects showed three novel amino acid substitutions. In subject 1 (a black individual), a single base substitution (AAG ---AGG) at codon position 48 changes amino acid residue lysine to arginine. In subject 2 (a white individual), a single base substitution (CGT----AGT) at codon 28 changes arginine to serine. In subject 3 (a black individual), a different base substitution at position 28 (CGT----CTT) changes arginine to leucine. These mutations occur at positions of the alpha l domain where other mutations have also been described, indicating that the normal residues at these positions play an important role in spectrin dimer self-association and thus, in membrane stability. PMID- 1878598 TI - Hairy cell leukemia: splenectomy after alpha 2b-interferon therapy. PMID- 1878599 TI - Rapid functional assay for the detection of multidrug-resistant cells using the fluorescent dye rhodamine 123. PMID- 1878600 TI - Diagnosis of chronic granulomatous disease. PMID- 1878601 TI - Inhibition of interleukin-2-induced tumor necrosis factor release by dexamethasone: does it reduce the antitumor therapeutic efficacy? PMID- 1878602 TI - [Trends in cancer mortality]. PMID- 1878603 TI - [Estimation of cancer incidence in France]. AB - National cancer incidence rates are not available in most countries. An estimation of the national cancer incidence from regional incidence data in France is proposed here. National cancer incidence rates (1978-1982) were estimated from the incidence and the mortality observed during the same period in five French departments with a cancer registry and from national mortality data. The cancer registries used for this estimation are: Bas-Rhin, Calvados, Cote d'Or, Doubs and Isere. The estimation was performed assuming that, for a given cancer site, sex and age group, the mortality/morbidity ratio is the same in the aggregate of the five departments and in France as Crude, age-specific and standardised on world population incidence rates were estimated for the most frequent cancer sites and for each sex. An estimation of the annual number of cases in France between 1978 and 1982 for the main cancer sites is also given. PMID- 1878604 TI - Genetic and molecular approach for breeding and use of laboratory fish for the detection of agents with carcinogenic and/or promoting activity. AB - Xiphophorine fish from wild populations are insusceptible to develop neoplasia. In contrast, certain backcrosses of Xiphophorus maculatus (platyfish) with Xiphophorus helleri (swordtail) as the recurrent parent, produce offspring that develop neoplasia in a Mendelian fashion. We concentrated our research on melanoma. The starting signal for the development of melanoma comes from an accessory v-erbB-related oncogene, x-erbB*, which is highly homologous to the human EGF receptor gene, and is part of a platyfish-specific tumor gene-complex designated as Tu. Normally, the platyfish is protected from its own Tu by Tu specific regulatory gene systems. The swordtail has neither evolved the Tu complex nor the regulatory gene systems. Therefore, the backcross procedure dismantles the regulatory gene systems thus permitting Tu-directed melanoma formation. x-erbB* derived from the platyfish, together with the swordtail derived oncogenes src, sis, pdgf-r, ras, myc, erbA are expressed or overexpressed in the melanoma, and inositol lipid turnover is considerably elevated. x-src and inositol lipid turnover have also been found elevated in the healthy tissues (eg brain) of the tumourous fish. To construct a fish strain which is highly susceptible to mutagenic carcinogens, we introduced a particular regulatory gene, ie an oncosuppressor gene (Bs), into the genome of the animals developing Mendelian inherited melanoma, by introgressive breeding. Bs prevents the strain from germ line-inherited melanoma but, following carcinogen-induced impairment in a somatic cell gives rise to the Tu-directed development of clonal melanoma in a particular fish, x-src activity and inositol lipid turnover are elevated in the tumor but, in contrast to the animals bearing the inherited melanoma, are not elevated in the brain. Promoting carcinogens (tumor promoters) do not induce melanoma in this strain. Similarly, in order to breed a fish strain susceptible to tumor promoters, we introduced a regulatory gene (the oncostatic gene g, golden) coding for a pre-transformational arrest of pigment cell differentiation in the stem cell stage of the fish that develop the Mendelian inherited melanoma. The new strain is incapable of developing melanoma. Its x-src activity and inositol lipid turnover is elevated in the brain indicating that the biochemical processes which were found to be correlated with the hereditary melanoma formation, are running in the new strain without the occurrence of melanoma. Following treatment with tumor promoters that overcome the arrest of pigment cell differentiation, melanoma develops within a very short latent period. PMID- 1878605 TI - [Tumor regression as a prognostic factor in breast cancer]. AB - Two hundred and fifty evaluable patients with breast cancer entered a protocol combining neoadjuvant and consolidation therapy by vinblastine (V), thiotepa (T), methotrexate (m) and 5-fluorouracil (f) (VTMF) with or without Adriamycin (A) (Doxorubicin; Adria Laboratories, Colombus, OH USA), and radiation therapy as exclusive locoregional treatment. Tamoxifen was given to 195 patients, 130 post menopausal and 65 pre-menopausal, and was omitted in 55 patients (31 postmenopausal and 24 pre-menopausal). There were 19 stage I, 86 IIa, 51 IIB, 36 IIIA and 58 IIIB. Primary chemotherapy induced tumor volume regression of more than 75% in 41% of the patients and complete clinical regression in 30% of the patients. The 5 years DFS rates were 100% for stage I, 82% for stage IIA, 61% for stage IIB, 46% for stage IIIA and 52% for stage IIIB patients. Among the 72 primary relapses there were 39 distant metastases, 6 locoregional and distant metastasis and 27 isolated locoregional metastases. The actuarial rate of locoregional recurrence is 13% for T2, 18% for T3, 19% for T4. At 5 years the rate of breast preservation was 94%. Cosmetic results are excellent or good for most patients. The 5 years overall survival (OS) were 95% for stage I, 94% for stage IA, 80% for stage IIB, 60% for stage IIIA and 58% for stage IIIB. In multivariate analysis tumor regression appears as an independent and significant factor. This parameter should be preserved in many patients with infiltrative breast cancer. PMID- 1878606 TI - [Concomitant association of radiotherapy and chemotherapy in inflammatory breast cancer. Initial results of phase II trial]. AB - Between 01/1986 and 12/1987, 15 patients displaying inflammatory breast carcinoma, were included in a phase II trial. The aim of the treatment was to increase the local response by the potentiation of radiotherapy by concomitant chemotherapy (continuous infusion 5 FU, vindesine, Cyclophosphamide). This treatment consisted of four series of radiotherapy: 18 Gy/10 fractions/12 days spaced by a 2-week rest period between series, to a total dose of 72 GY to the breast tumor. Chemotherapy was undertaken over the first 5 days of radiotherapy in each series. Two patients had metastatic disease (bone-liver). Seven patients had not responded to an initial standard chemotherapy treatment. Six patients were initially treated with the concomitant association. The treatment was very well tolerated by all 15 patients. Inflammation disappeared in all patients within 6 weeks after the beginning of the association. A tumor decrease was observed in all patients, complete in 60%. All 7 patients who had failed initial chemotherapy recurred 8 to 19 months after the association, despite a good response; 3 died of disease and 4 were in local or metastatic evolution on last follow up. The 6 patients treated initially with the association Radiotherapy/Chemotherapy were all alive with a 27 months median follow up (24 40). 2/6 mastectomies were performed: one for breast recurrence and one for persistent residual mass. In this latter patient histologic examination showed no residual active tumor. 4/6 patients have their breast preserved without sequelae. High local response rates were observed with the concomitant combination of radiotherapy and chemotherapy, specially when administered as initial treatment. PMID- 1878607 TI - [Fotemustine: a pilot phase II trial in sarcoma of the soft tissues]. AB - Fotemustine has been administered to 10 patients with metastatic or redux soft sarcoma in a phase II pilot study. The main inclusion criteria were: at least one measurable site, Karnofsky index (KI) higher than 60%, no specific treatment within the last 4 weeks, correct haematological status. Induction treatment comprised fotemustine 100 mg/m2 D1-D8-D15 in a 1 h intravenous infusion protected from light, followed by a 5-week rest period. In patients with no progressive disease, maintenance treatment comprised fotemustine 100 mg/m2 D1 q 3 weeks, until progression or toxicity. Patients characteristics were: 9 M/1 F; median age: 51 years [26-66]; median KI 90% [60-100]; median number of previous drugs: 5 [2-8]; 6 patients had two or more metastatic sites and one patient had developed a sarcoma following chest radiotherapy. Evaluation was carried out in weeks 4 and 8, following the first fotemustine injection. One case of minor response and one case of stabilisation were observed, but they were of short duration. The main toxicity was haematological with delayed leucopenia and thrombopenia (nadir: week 6). In patients who have undergone previous chemotherapy, fotemustine is not efficient according to the first step of the Gehan statistical guidelines. PMID- 1878608 TI - [Secretion by Candida albicans of substances stimulating the proliferation of a cell line of malpighian epithelioma of the mouth]. PMID- 1878609 TI - Burnout as a risk factor for coronary heart disease. AB - During the preparation of a prospective study of exhaustion as a precursor of myocardial infarction (MI), the authors found that many coronary patients said that they had been burned out at some time in their lives. Therefore, the question, "Have you ever been burned out?" was included in the study. The cohort was formed by 3,877 men, aged 39 to 65, and was followed up on for 4.2 years. Among the men who were free of coronary heart disease (CHD) at screening, 59 subjects experienced a fatal or nonfatal myocardial infarction during follow-up. Those who endorsed the above question when they entered the study were found to be at increased risk for myocardial infarction when the authors controlled for age, blood pressure, smoking, and cholesterol; RR (relative risk) = 2.13; p less than .01. About one third of those who were exhausted before myocardial infarction had been burned out at some time in their lives, chi 2 = 7.09, p less than .01. The data indicate that a state of exhaustion before myocardial infarction is often a reactivation of earlier periods of breakdown in adaptation to stress. PMID- 1878610 TI - Work resumption and leisure activities after cardiac rehabilitation: the development of criteria to measure social recovery. AB - In a multicentered trial, the authors investigated 280 cardiac patients to determine the level of recovery of their social life after they had completed a physical training program. Data on work and leisure activities (sports, hobbies, social contacts, and odd jobs) were obtained immediately before and after rehabilitation and again 12 months later by means of semistructured interviews and an inventory of leisure activities. For the analysis of leisure variables, they developed a classification procedure to assign patients to one of five categories indicating an unchanged good outcome, significant recovery, nonparticipation, significant deterioration, or an unchanged poor outcome. The results after rehabilitation showed that some patients had benefited more than others. In addition, improvement or deterioration in one aspect of social recovery appeared to be independent from other aspects. Further systematic research is needed to determine which factors influence the amount of benefit derived from rehabilitation. PMID- 1878611 TI - Immunological and psychosocial predictors of disease recurrence in patients with early-stage breast cancer. AB - Ninety women with recently diagnosed stage I or stage II breast cancer who had been admitted to the NIH Clinical Center and were participating in a randomized trial were entered onto this behavioral immunology protocol. Patients were immunologically and psychosocially assessed at baseline (approximately 5 days after surgery) and again at 3 and 15 months post surgery. All of the patients were followed up for a minimum of 5 years, and 60% of the patients were followed for 7 years or longer. Twenty-nine women in the study group reported disease recurrences over the entire follow-up period. Causal path modeling statistical techniques showed that natural killer (NK) cell activity was a strong predictor of disease outcome when the outcome variable was defined as recurrence v nonrecurrence of disease (chi 2 = 6.9, p less than .001). Higher NK cell activity at follow-up predicted disease-free survival over the follow-up period. When the disease outcome variable was operationally defined as time to recurrent disease, the psychosocial factors were more strongly predictive of the rate of disease progression for those who had a recurrence (chi 2 = -4.1, p less than .01), but NK cell activity was seemingly less relevant in this latter case. Overall, these findings suggest that including mood and potentially relevant immunological variables, along with important biological prognostic variables, in multivariate and prospective models such as those examined in this study, potentially contributes more to the explanation of greater outcome variance of early-stage breast cancer than has been believed in the past. PMID- 1878612 TI - Effectiveness of a videotaped behavioral intervention in reducing anxiety in emergency oral surgery patients. AB - This study evaluated the effectiveness of a videotaped behavioral treatment program in reducing dental anxiety in emergency oral surgery patients. It compared a videotaped placebo program and a no-treatment control condition. Anxiety, measured for two periods during the study (an anticipatory phase just before oral surgery and a post oral surgery phase), was evaluated by means of self-report, physiological, and behavioral observation measures. Results revealed significant treatment group as well as Group X Sex interaction effects for the heart rate index of physiological arousal. Results also revealed that the treatment program was reported by subjects to be significantly more helpful than the placebo program. Overall, these results suggest that a short, videotaped behavioral intervention can have a positive effect on the oral surgery patient, and that the sex of the subject may be an important variable to be incorporated in evaluating the effectiveness of this type of treatment program. PMID- 1878613 TI - Psychosocial and physiological correlates of male gender role stress among employed adults. AB - Previous research has identified male gender role stress (MGRS) as a construct that leads men, as a function of traditional socialization processes, to appraise certain situations in ways that produce psychosocial and physiological distress. Because the initial research was based on college undergraduates, the current study explored the relationship of MGRS to psychosocial and physiological risk factors for cardiovascular disease among employed adults. As predicted, men obtained significantly higher scores than women on a measure, the MGRS Scale, developed to assess this construct. Women with elevated MGRS Scale scores, however, experienced undesirable outcomes much the same as their male counterparts. Specifically, MGRS Scale scores were significantly associated with Type A behavior, hostility, personal loss, life dissatisfaction, and elevated systolic and diastolic blood pressure. The authors discuss possible environmental contributors to the development and maintenance of MGRS, including organizational factors associated with male-dominated work environments. PMID- 1878614 TI - Impulsive artistic creativity as a presentation of transient cognitive alterations. AB - A 27-year-old right-handed male mosaic artisan who had not shown any interest in drawing or artistic activity was admitted to the Department of Neurology for attacks of bizarre behavior and convulsive disorder. The patient reported feeling "waves" engulfing him during the attacks, leaving him floating helplessly. During some attacks, the patient impulsively initiated drawing activity. Interictal sleep-deprivation EEG showed a left frontotemporal focus of paroxysmal discharge. Brain tomography with SPECT showed low 99Tc-HMPAO uptake in the left frontoparietal region. Psychodiagnostic tests gave evidence of dysfunction of the left frontal region, with preference of the right hemisphere. It is suggested that the attacks of altered cognitive state were, in this case, provoked by spreading depression of the left hemisphere, while the integrative functions of the right hemisphere remained intact. Thus, the impulsive artistic creativity during the attacks may represent a "release phenomenon" of the complex visuospatial skills of the right (subdominant) hemisphere. This symptomatology of transient cognitive alterations is unique and, to the best of our knowledge, has not been previously reported. PMID- 1878615 TI - Smoking policies in hospitals. PMID- 1878616 TI - The practical business of treatment--16. Can't treat, won't treat? Alcoholic liver disease. AB - An alcohol intake of more than 35 units per week will predispose to alcoholic liver disease, although not all patients with alcohol-induced liver damage have a dependency syndrome and only about 20% of those with an unremitting heavy alcohol intake will develop liver disease. In those with evidence of chronic liver disease, a liver biopsy is the most important investigation because it confirms the diagnosis and is indicative of the prognosis. Abstinence remains the mainstay of treatment and a multi-disciplinary approach is the best way to achieve this in most cases. In patients with severe alcoholic hepatitis, specific therapies such as high dose corticosteroids and propylthiouracil have shown promising results but are still under evaluation. Liver transplantation has been used successfully in patients with recurrent complications arising from portal hypertension, but whether a minimum period of abstinence should be a requirement remains the subject of debate. PMID- 1878617 TI - Tobacco addiction and control in Spain. AB - In Spain there is a high prevalence of smokers: 39.2% in the general population, 61.9% of the working population, and 35% of doctors. At the same time, health education on smoking is inadequate, and tobacco is cheap. As a result, it is difficult to implement legislation which bans or restricts smoking in some areas. It is clear that more education on smoking and health is needed at every level of the Spanish population. PMID- 1878618 TI - Tobacco prevention in hospitals needs prolonged and sustained effort. AB - The smoking control, policy implemented at a Barcelona hospital over a 3-year period resulted in a reduction of smoking in the hospital and a raised awareness of the exemplary role health professionals can have. However, participation by health professionals in the project decreased over the 3-year period. Although reduced, the smoking rate in the hospital still is at a high level; this should trigger health professionals to further exploit their potential in smoking reduction efforts. PMID- 1878619 TI - Hospital smoking policies: examples of good practice? AB - Health services should be taking a lead in implementing smoking policies which promote smoke-free environments for patients, visitors and staff, and ensure that patients and staff are provided with information and advice about smoking and how to give it up. Yet the evidence suggests that the implementation of such policies is patchy, particularly in countries where there are high smoking rates amongst health workers, including doctors. This article discusses, in the light of experience from Spain and the UK, some of the factors which are important in determining the success of such programmes. It is argued that such programmes will be of benefit to the future health of both patients and staff. PMID- 1878620 TI - Tobacco prevention in hospitals. The British experience. AB - There are three themes in this paper of interest to a UK audience. The first draws attention to the importance of congruity between the hospital environment and education about the harmfulness of smoking. A smoking policy is an integral part of the education process. Secondly, there are clear benefits to accrue from combining several educational elements in one smoking control programme, which has a synergistic effect. Thirdly, hospital staff are health promoters, too, and their training should reflect the importance of their public health role. PMID- 1878621 TI - Tobacco prevention in hospitals: long-term follow-up of a smoking control programme. AB - This paper presents the results of a smoking control programme carried out in Sant Jaume i Santa Magdalena Hospital in Mataro (Barcelona, Spain) involving the entire hospital staff. The general objectives of the programme were: (1) to reduce tobacco consumption among hospital staff and (2) to create an awareness of their exemplary role as health professionals. In order to achieve these aims, different activities were carried out: lectures on the consequences of smoking; restrictions on smoking in hospital areas; and smoking cessation help for those who wished to give up smoking. To measure the effectiveness of the intervention, a survey of smoking habits and attitudes among the hospital staff was conducted before the start of the programme in 1986 and repeated two and a half years later in 1989. The population studied in both surveys (n = 298 and n = 304) was similar by sex, age, and professional status. Regarding tobacco consumption there was the same proportion of never smokers, while the percentage of current smokers was reduced by 11 between the two surveys (51 to 40%), and the ex-smokers group showed an increase (16 to 23%). These differences were significant. There was also a remarkable change in attitudes among the health professionals, especially with regard to their disposition to give advice to stop smoking. The results show a reduction of the prevalence of smoking among the hospital staff and a positive change in their attitudes towards smoking. PMID- 1878622 TI - Increased severity of alcohol withdrawal in in-patient alcoholics with a co existing anxiety diagnosis. AB - The purpose of this study was to determine whether alcoholics with a co-existing anxiety disorder (dual-diagnosed group) experienced different withdrawal symptomatology from alcoholics without an anxiety disorder (alcohol-only group). Symptoms of alcohol withdrawal were measured on admission to an in-patient treatment program and throughout treatment (days 0, 2, 7, 14 and 21) using the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale. The dual-diagnosed group exhibited more severe alcohol withdrawal, as indicated by higher total CIWA-Ar scores, at all time points than the alcohol-only group. The possibility that anxiety disorders and alcohol withdrawal share a common neurochemical basis and that the CIWA-Ar scale may be useful as a screening instrument for anxiety disorders in alcoholics is discussed. PMID- 1878623 TI - The motivation for change from problem alcohol and heroin use. AB - This paper provides an overview of the first study in Switzerland on spontaneous remission from substance abuse, conducted 1988. After a rigourous screening process, 60 practically treatment-free remitters could be identified. While 14 of the 30 alcohol cases reduced their consumption almost to abstinence, all but two heroin remitters stopped their consumption altogether. No selection bias could be detected when comparing the groups studied with clinic populations, survey data and police records. The qualitative analysis of the collected extensive life histories led to a typology of the autoremission process. The motivation to change, the implementation of the decision, the maintenance and the negotiation of a new identity or meaning in life represent the three major stages. This paper focuses on the first stage and the role of negative vs positive experiences in setting off subsequent changes in alcohol or heroin consumption. The variation in the motivational background is illustrated by a close look at the rich life history accounts as well as by quantitative data on life events and cognitive prerequisites of change. Methodological drawbacks of this first exploratory study, such as recall problems and a narrow definition of addiction excluding psychological problems, are discussed and the necessity of future prospective studies is underlined. PMID- 1878624 TI - Like parent like child? Associations between drinking and smoking behaviour of parents and their children. AB - This paper examines the association between the smoking and drinking behaviours of parents and their adolescent children, and the effect of gender and social class upon this association. It is based on data collected from a cohort of young people and their parents, resident in the west of Scotland. Both social class and parental smoking behaviour were independently associated with young people's smoking, with young people from lower social class households or whose parents smoked being most likely to smoke. Social class and gender were independently associated with young people's drinking, with males and young people from non manual households being most likely to drink. Parental drinking behaviour was associated positively with young people's drinking only in non-manual classes and among daughters. We conclude that it is important to take social class and gender into account since it may influence whether or not there is an association between the behaviour of young people and that of their parents, and it may influence young people's behaviour in addition to influences from parental behaviour. PMID- 1878625 TI - Symptoms and correlates of anabolic-androgenic steroid dependence. AB - Forty-nine male weight lifters, all users of anabolic-androgenic steroids (AASs), completed an anonymous, self-administered questionnaire to investigate addictive patterns of use. At least one DSM-III-R symptom of dependence was reported by 94% of the sample. Three or more symptoms, consistent with a diagnosis of dependence, were reported by 57%. Dependent users (n = 28) could be distinguished from non dependent users (n = 21) by their use of larger doses, more cycles of use, more dissatisfaction with body size, and more aggressive symptoms. Multiple regression analysis revealed that dosage and dissatisfaction with body size were the best predictors of dependent use. Patterns of other substances used, although not predictive of AAS dependence, revealed very low cigarette use and at the same time high alcohol consumption. These data support the notion that AASs are addicting, and suggest that dissatisfaction with body size may lead to dependent patterns of use. The implications for both prevention and treatment are discussed. PMID- 1878626 TI - Drinking on television: a content analysis of recent alcohol portrayal. AB - The portrayal of alcohol on British television was examined in a systematic sample of 50 programmes broadcast in 1988. Nearly three-quarters of the programmes contained visual or verbal references to alcohol. On average, there was a reference to alcohol in every six and a half minutes of programming. Alcohol was most prominently featured in fictional programmes, particularly in one soap opera, Eastenders. A third of the programmes showed specific brands of alcohol. It is estimated that the portrayal of alcohol in Britain's most popular programmes is worth pounds 487 million of free promotion to the alcohol industry per annum. Nevertheless, in comparison with an earlier study, carried out in 1986, there appeared to be fewer alcohol images. A number of recommendations are made for further action and monitoring of alcohol portrayal. PMID- 1878627 TI - Sharing spoons: a risk factor for HIV-1 infection in Vienna. AB - Sharing of needles and syringes plays a central role in HIV-1 transmission among intravenous drug users (IVDUs). There have been several suggestions to protect the injecting population from further harm, but focused mainly on the use of sterile needles and syringes as well as information about safer sexual behavior. This study examined a total of 366 IVDUs at the drug dependence out-patient ward of the Psychiatric University Clinic of Vienna. HIV-1 antibodies were found in 29.7% (58) in 1989 and in 26.9% (42) in 1990. The results show that in 1989 14% and in 1990 5% IVDUs who never shared needles or syringes or other drug paraphernalia were found to be HIV-1 positive. In spite of the high information standard among Viennese drug addicts on risk reduction, the underestimated co factors during drug administration might be responsible for a further HIV-1 transmission. Educational interventions on this subject should address even IVDUs who do not share needles and have adjusted to 'safer sex' practices. PMID- 1878628 TI - Cannabis use in a large sample of acute psychiatric admissions. AB - A sample of 908 patients drawn from two London Psychiatric Hospitals is described in terms of age, sex, self-reported drug and alcohol history, drug urinalysis results and initial psychiatric diagnosis. Some (34.5%) of respondents admitted to using cannabis at least once in their lifetime and 13% of those tested had urines positive for cannabis on admission. Cannabis use is commoner in young males. These is a higher likelihood that an initial diagnosis of 'psychosis' will be made at admission if patients either report use of cannabis or present a urine sample positive for cannabis. PMID- 1878629 TI - Familial history of opium use and reported problems among opium addicts in Pakistan. AB - One-hundred and twenty-nine opiate addicts on a monthly maintenance regimen were studied. Subjects with a positive family history of opium use had an earlier age of onset than the subjects without a family history of opium use. Self-reported psychosocial problems resulting from opium use were documented in only seven subjects. Individuals who began opium use after 1979, when it became illegal to use the drug, had a significantly later age of onset than subjects who began before 1979, suggesting that negative legal sanctions can delay initiation of opium consumption. PMID- 1878630 TI - Abuse of neuroleptic drugs. PMID- 1878631 TI - Cigarette sales in New Zealand. PMID- 1878632 TI - Outpatient treatment for alcohol abusers. PMID- 1878633 TI - The consequences of child sexual abuse. PMID- 1878634 TI - What now for IPPNW? PMID- 1878635 TI - The practice manager. PMID- 1878636 TI - Helen Mackay, another iron lady. PMID- 1878637 TI - New dietary reference values. PMID- 1878638 TI - Comparison of breast carcinomas diagnosed in the 1980s with those diagnosed in the 1940s to 1960s. AB - OBJECTIVE: To find out if breast carcinomas diagnosed in the 1980s differ from those diagnosed a few decades ago. DESIGN: Retrospective comparative cohort study. SETTING: City of Turku, south western Finland. PATIENTS: 439 patients with breast carcinoma diagnosed in 1945-65 with a median follow up of 27 years (95% of all those histologically diagnosed in Turku); and 370 patients with breast carcinoma diagnosed in 1980-4 with a median follow up of 6 years (94% of all those histologically diagnosed in Turku). MAIN OUTCOME MEASURES: Breast cancer incidence, mortality from breast cancer, age at diagnosis, stage of cancer, seven histological factors, DNA ploidy. RESULTS: Age adjusted incidence of breast cancer increased from 30.8/100,000 person years in 1953-7 to 62.2/100,000 in 1983 7; mortality in breast cancer increased from 16.7 to 17.2/100,000 person years. Survival of patients with stages II to IV (but not with stage I) improved. The mean age at diagnosis increased from 55.5 years in 1945-55 to 62.5 years in 1980 4 (p less than 0.0001); the proportion of patients with T0-1 carcinomas increased from 13% to 41% (p less than 0.0001) and with pN0 carcinomas from 43% to 55% (p = 0.003) from 1945-65 to 1980-4. There was no change in histological type or DNA ploidy of breast cancer, but in the 1980-4 cohort carcinomas were more often well differentiated, had lower mitotic counts and less nuclear pleomorphism, more often had a well defined tumour margin, and had less tumour necrosis. There was, however, no difference between the two cohorts in these histological characteristics except for tumour necrosis when they were compared in a multivariate log linear model at a given size of primary tumour. CONCLUSION: Improved survival with breast cancer can at least partially be explained by detection of increased numbers of small carcinomas with favourable histological characteristics. PMID- 1878639 TI - Insulin dependent diabetes in childhood and material deprivation in northern England, 1977-86. AB - OBJECTIVE: To determine the incidence of insulin dependent diabetes in the Northern region of England in children less than 16 years old in the period 1977 to 1986 and to relate the incidence data to an index of deprivation. DESIGN: Retrospective analysis of hospital case records identified from the regional health authority's computer; validation of the primary source with hospital clinic registers and community paediatric registers. SETTING: Northern region, excluding South Cumbria District Health Authority (659,300 children under 16 in 1981). PATIENTS: All children diagnosed with insulin dependent diabetes before the age of 16 and resident in the region at time of diagnosis. MAIN OUTCOME MEASURES: Incidence rates for the 10 year period and analysis of incidence rates within categories of deprivation. RESULTS: 919 incident cases were identified. The validation procedure covered 54% of all cases identified and gave 95% completeness of ascertainment. The average annual incidence over the 10 year period was 14.8/100,000 for girls and 13.4/100,000 for boys. The annual incidence for the most and least deprived areas of the region was 18.7/100,000 (95% confidence interval 16.2 to 21.5) for boys and 7/100,000 (5.6 to 8.8) for girls. There was a highly significant trend (p less than 0.001) of decreasing incidence with decreasing level of deprivation. CONCLUSIONS: In the north of England the incidence of childhood diabetes is related to material deprivation. PMID- 1878640 TI - Renal disease, epidermal necrosis, and epithelial cell antibodies. AB - OBJECTIVE: To describe the association between epithelial cell IgM, which has previously been associated with an increased incidence of loss of renal graft in children, with a novel cutaneous eruption and unexplained native renal disease. DESIGN: Observational study on children with epithelial cell antibody presenting with unexplained renal or skin disease. SETTING: General paediatric department and regional paediatric nephrology unit. PATIENTS: Six children (five girls, one boy), who presented to the unit in 1989-90. RESULTS: Three children, two of whom had a history of a hyperpigmented rash, presented with hypertension, proteinuria, and impaired renal function. Renal biopsy specimens from two of these children showed severe arteriolar endothelial cell swelling with arteriolar occlusion. These children fully recovered after treatment with antihypertensive drugs. The third child developed end stage renal failure and required dialysis. Three other children presented with an unusual cutaneous eruption but no evidence of renal disease. Histology of the skin lesions showed acute epidermal necrosis and features consistent with a viral infection. CONCLUSIONS: The aetiology and pathogenesis of the epithelial cell antibody are unknown. These cases indicate that it may have a role in native kidney disease and focal epidermal necrosis. Clinical and histological features suggest that the antibody may be associated with a viral infection. PMID- 1878641 TI - Growth of asthmatic children during treatment with budesonide: a double blind trial. AB - OBJECTIVE: To determine whether the inhaled glucocorticosteroid budesonide has any adverse effect on short term linear growth in children with mild asthma. SETTING: Outpatient clinic in secondary referral centre. PATIENTS: 15 children aged 6-13 years with normal statural growth velocity during the previous year, no signs of puberty, and no use of systemic or topical steroids in the two months before the study. DESIGN OF INTERVENTIONS: Double blind, randomised crossover trial with two active periods in which budesonide was given in divided daily doses of 200 micrograms and 800 micrograms. During run in and two washout periods placebo was given. After the second washout period the children received open treatment with 400 micrograms budesonide daily. All periods were of 18 days' duration. MAIN OUTCOME MEASURE: Growth of the lower leg as measured twice a week by knemometry. RESULTS: Mean growth velocity of the lower leg was 0.63 mm/week during run in and during washout 0.64 mm/week. Budesonide treatment was associated with a significant dose related reduction of growth velocity: the mean reduction in growth velocity during treatment was 0.11 (95% confidence interval 0.15 0.36 (0.13 to 0.59) mm/week with 800 micrograms budesonide (p less than 0.05; Page's test). During treatment with 400 micrograms budesonide a reduction of 0.17 (-0.10 to 0.45) mm/week was found. CONCLUSIONS: Treatment with inhaled budesonide is associated with a dose related suppression of short term linear growth in children with mild asthma. PMID- 1878642 TI - Increased birth weight in northerly islands: is fish consumption a red herring? PMID- 1878643 TI - In praise of non-fundholding practices. PMID- 1878644 TI - Variations in budgets of fundholding practices. PMID- 1878645 TI - Fundholding and cash limits in primary care: blight or blessing? PMID- 1878646 TI - Controlled trials in single subjects. 1. Value in clinical medicine. PMID- 1878647 TI - Controlled trials in single subjects. 2. Limitations of use. PMID- 1878648 TI - ABC of antenatal care. Vital statistics of birth. PMID- 1878649 TI - The health of the nation. PMID- 1878650 TI - Surgeons who are hepatitis B carriers. PMID- 1878651 TI - Limiting the number of oocytes and embryos transferred in GIFT and IVF. PMID- 1878652 TI - Birth weight as a risk factor for raised blood pressure. PMID- 1878653 TI - Wheezing or asthma. PMID- 1878654 TI - Daughters of stilboestrol. PMID- 1878655 TI - Diagnosing pancreatic masses. PMID- 1878656 TI - Genetics and lung disease. PMID- 1878657 TI - Creutzfeldt-Jakob disease and blood transfusion. PMID- 1878658 TI - Complications of pregnancy and delivery and psychosis in adult life. PMID- 1878659 TI - Anaesthetists' role in introducing audit into surgery. PMID- 1878660 TI - Target payments for cervical smears. PMID- 1878662 TI - Proceedings of the seventeenth annual meeting of the European Group for Bone Marrow Transplantation. 27-31 January, 1991, Cortina d'Ampezzo, Italy. PMID- 1878661 TI - Uptake of cervical smear testing among travellers. PMID- 1878663 TI - Donor cell leukaemia after bone marrow transplantation for severe aplastic anaemia. PMID- 1878664 TI - Androgen dependence in patients with severe aplastic anemia after antilymphocyte globuline therapy. PMID- 1878665 TI - Bone marrow transplantation (BMT) for acquired severe aplastic anaemia (SAA): long term follow-up of 107 consecutive patients. PMID- 1878666 TI - New approach of treatment of severe aplastic anemia. Cooperative Group on the Treatment of Aplastic Anemia. PMID- 1878667 TI - How do BMTs cure leukaemia? New directions. PMID- 1878668 TI - What is graft versus host disease? PMID- 1878669 TI - Unrelated bone marrow transplant. Use of IL2 receptor monoclonal antibody (IL2-R Ab) in prophylaxis of GVHD. The GEGMO Group. PMID- 1878670 TI - Study on the hematopoietic stem cells from umbilical cord blood. PMID- 1878671 TI - Mother as HLA haploidentical marrow donor for children with advanced leukemia. PMID- 1878672 TI - Unrelated donor marrow transplantation: an interim analysis of the international marrow unrelated search and transplant (IMUST) Study. II. PMID- 1878673 TI - Improvement of communications between existing European registries by use of telematic system. PMID- 1878674 TI - Bone marrow donors worldwide (BMDW). PMID- 1878675 TI - The dose of total body irradiation (TBI), and GvHD prophilaxis have a crucial role on relapse risk and survival after BMT for leukaemia. PMID- 1878676 TI - VP16 and TBI as conditioning regimen for allogeneic BMT in patients with high risk and relapsed ALL and NHL. PMID- 1878677 TI - Allogeneic BMT versus autologous BMT in childhood acute lymphoblastic leukemia (ALL): an Italian cooperative study of vincristine (VCR), F-TBI and cyclophosphamide. AIEOP (Associazione Italiana Ematologia ed Oncologia Pediatrica) Italy. PMID- 1878678 TI - Relative toxicity of two different conditioning regimens in patients undergoing allogeneic bone marrow transplantation. PMID- 1878679 TI - BAVC regimen in CR AML patients. PMID- 1878680 TI - Variation in statistical reports and analysis on one and the same medical question. The Leukemia Working Partly. PMID- 1878681 TI - Documentation of the EBMT solid tumor registry (STR) data. A "crux (? or X) for doctors"? PMID- 1878682 TI - Effect of IL-1 and TNF-alpha on early progenitor cells: implications for bone marrow purging. PMID- 1878683 TI - Liquid marrow serum-free culture in patients acute lymphoblastic leukemia a potential application to purge marrow for autologous transplantation. PMID- 1878685 TI - High-dose chemotherapy with autologous bone marrow rescue: haematopoietic reconstitution by non-cryopreserved marrow. PMID- 1878684 TI - The Parma international randomized study in relapsed non Hodgkin lymphoma: 1st interim analysis of 128 patients (as 15 January 1991: 153 patients). PMID- 1878686 TI - IL-2 treatment after autologous bone marrow transplantation in poor prognosis Hodgkin's disease: defective IL-2-induced LAK activity? PMID- 1878687 TI - Use of recombinant IL-2 (RU49637) after autologous bone marrow transplantation (BMT) in patients with hematological neoplasias: a phase 1 study. PMID- 1878688 TI - Monoclonal anti TNF alpha antibody in the treatment of acute GvHD refractory both to corticosteroids and anti IL-2 R antibody. PMID- 1878689 TI - Prospective randomized study of GVHD prevention using an anti IL2 receptor (CD25) MoAb after allogeneic bone marrow transplantation (BMT). PMID- 1878690 TI - The dose-response effect: a critical analysis. PMID- 1878691 TI - European Bone Marrow Registry in solid tumors: 7 years of experience. PMID- 1878692 TI - Kinetics of relapse of leukemia after bone marrow transplantation: cytogenetic follow up of patients with chronic myelogenous leukemia. PMID- 1878693 TI - Bone marrow transplantation for leukaemia in Europe. Report from The Working Party Leukaemia. PMID- 1878694 TI - Patterns of relapse after bone marrow transplantation for chronic myeloid leukaemia. PMID- 1878695 TI - Cytogenetic follow-up after allogeneic bone marrow transplantation for Ph+ CML: update of the European Cooperative Study. PMID- 1878696 TI - Alloimmune effects of bone marrow transplantation for leukaemia on the leukaemic diseases. PMID- 1878697 TI - Karyotype and BCR studies after bone marrow transplantation for chronic myeloid leukaemia. PMID- 1878698 TI - An assessment of chimeric transcript detection in CML patients after bone marrow transplantation. AB - The Polymerase Chain Reaction (PCR) was used to evaluate minimal residual disease in 21 Ph+ CML patients at various intervals after allogeneic bone-marrow transplantation (ABMT) by amplification of bcr-abl cDNA. All patients were cytogenetically Ph- at the moment of molecular analysis. Of these 76% were PCR negative, 24% positive for bcr-abl transcripts. 100% of the Cyclosporine A/Methotrexate treated patients (7/7) were negative. Severe chronic GvHD was twice as frequent in PCR positive patients (60%) than in negative ones (31%). The only patient who relapsed during follow up was PCR positive. The two longest survivors were PCR negative. These data are still insufficient for assessing the predictive value of PCR analysis in CML. Patients. 25 patients with Ph+ CML at diagnosis were enrolled in this study. Two died soon after BMT because of infection for failure of engraftment/early relapse, two were Ph chromosome positive and PCR+, and were therefore dismissed from this study. All remaining 21 patients were cytogenetically Ph- at the time of molecular analysis and underwent ABMT from matched donors. All patients were conditioned with cyclophosphamide and TBI: 330 cGy the three days prior to transplantation (990 cGy total, treatment B), or 200 cGy two times daily for three days (1200 cGy total, treatment A). In 3 cases the marrow was treated for GvHD prophilaxis with Campath alone or Campath plus BT 5/9 monoclonal antibodies (1). All patients were treated with Cyclosporin A (CS) 5 mg/kg i.v. from the day prior to transplantation until 25-30 days after; 9 of these were treated with CS plus Methotrexate (MTX). PMID- 1878699 TI - BCR-ABL transcripts detected by polymerase chain reaction (PCR) after allogenic BMT for CML: analysis of 32 longterm disease free patients. PMID- 1878700 TI - Persistence of BCR/ABL transcripts after BMT for CML detected by PCR reflects a high risk of relapse. PMID- 1878701 TI - Effects of alpha-IFN on chronic myeloid leukemia (CML) hematopoiesis maintained in long-term cultures. PMID- 1878702 TI - Is graft versus leukaemia separable from graft versus host disease? PMID- 1878703 TI - Intensive therapy for high grade multiple myeloma (MM). PMID- 1878704 TI - Autologous bone marrow transplantation with immunotoxin purged marrow for multiple myeloma. Long term results in 14 patients with advanced disease. PMID- 1878705 TI - Allogenic BMT for multiple myeloma (MM). The Italian experience. PMID- 1878706 TI - Allogeneic bone marrow transplantation in multiple myeloma using HLA-compatible sibling donors--an EBMT Registry Study. PMID- 1878707 TI - Methodology of evaluation in EORTC trials including BMT in acute myelogenous leukemia (AML) in first complete remission (CR). EORTC Leukemia Cooperative Group (LCG) and GIMEMA. PMID- 1878708 TI - Time intervals influence outcome of bone marrow transplantation (BMT) in patients with acute lymphoblastic leukemia. The Leukemia Working Party of EBMT. PMID- 1878709 TI - Allogeneic versus autologous bone marrow transplantation versus chemotherapy for treatment of acute myeloid leukemia in first complete remission (BGM 84 and BGMT 87 studies). The BGMT Group. PMID- 1878710 TI - Autologous marrow transplantation in first remission acute myeloid leukemia using marrow purged with mafosfamide. PMID- 1878711 TI - Idarubicin plus ARA-C followed by allogeneic or autologous bone marrow transplantation in advanced acute lymphoblastic leukemia. PMID- 1878712 TI - Bone marrow transplantation for myelodysplastic syndrome and secondary leukemia: outcome of 86 patients. PMID- 1878713 TI - Prognostic variables in bone marrow transplantation for secondary leukaemia and myelodysplastic syndromes: a survey of the working party on leukaemia. PMID- 1878714 TI - Immunological response in vitro by Candida after allogeneic bone marrow transplantation. PMID- 1878715 TI - Late marrow failure occurring after HLA identical bone marrow transplant. PMID- 1878716 TI - Levels of soluble low affinity IL2 receptors (s-IL2 R) and TNF in the serum after BMT. PMID- 1878717 TI - Male sexual function following bone marrow transplantation. PMID- 1878718 TI - Hepatic veno-occlusive disease following bone marrow transplantation treated by prostaglandin E1. PMID- 1878719 TI - Haemostatic changes in uncomplicated bone marrow transplants. PMID- 1878721 TI - Strategies for acute myelogenous leukemia. PMID- 1878720 TI - Early deaths in children after bone marrow transplantation: data of the AIEOP BMT Group. PMID- 1878722 TI - Progress in allogeneic and autologous BMT for acute lymphoblastic leukaemia (ALL). PMID- 1878723 TI - Effects of treatment regimens in patients allografted for acute and chronic myelogenous leukemia. PMID- 1878724 TI - Bone marrow transplantation for chronic myeloid leukaemia. PMID- 1878725 TI - The rationale of autologous bone marrow transplantation. PMID- 1878726 TI - Bone marrow transplantation from unrelated donors for genetic diseases following conditioning with Busulphan and Cyclophosphamide. PMID- 1878727 TI - Bone marrow transplantation in children and in adults with thalassemia. PMID- 1878728 TI - Bone marrow transplantation for adult patients with thalassemia major. PMID- 1878729 TI - Endocrine function after bone marrow transplantation for thalassemia. PMID- 1878730 TI - Persistence of mixed chimerism in class 3 thalassemic patients following BMT. PMID- 1878731 TI - Randomised placebo controlled study of RH-GM-CSF following ALG in the treatment of aplastic anaemia. PMID- 1878732 TI - The use of GM-CSF as an adjunct to autologous/syngeneic bone marrow transplantation: a prospective randomized controlled trial. PMID- 1878733 TI - RHU GM-CSF shortens aplasia duration after ABMT in non-Hodgkin's lymphoma: a randomized placebo-controlled double-blind study. PMID- 1878734 TI - Successful stimulation of autologous bone marrow recovery by GM-CSF and IL-3 after an unrelated donor BMT for juvenile CML complicated by graft failure. AB - We report the case of a boy with juvenile chronic myeloid leukemia (jCML), who after initial treatment with interferon alpha-2 (IFN) and hydroxyurea underwent bone marrow transplantation (BMT) from a matched unrelated donor complicated by graft failure. Subsequent stimulation of hematopoiesis by GM-CSF and IL-3 promoted autologous recovery. In contrast to the course of disease pre-BMT, the boy is now off any therapy remaining in complete remission more than 500 days after BMT. PMID- 1878735 TI - Human recombinant GM-CSF in allogeneic bone marrow transplantation for leukaemia: double-blind placebo controlled trial. AB - A double-blind randomised trial compared 20 patients with leukaemia receiving human recombinant granulocyte macrophage colony stimulating factor (GM CSF), with 20 patients receiving placebo for 14 days after allogeneic matched sibling bone marrow transplantation. The median neutrophil count at 14 days was significantly higher in the GM CSF group (1.90 vs. 0.46 x 10(9)/l). The duration of hospital stay, the number of antibiotic days, and the number of fever days was the same for both patient groups. The lymphocyte count was significantly higher in the GM CSF group than in the placebo group between days 10 and 15 after transplantation. The GM-CSF group had lower haemoglobin concentrations and platelets counts, and higher plasma urea creatinine and bilirubin, than the placebo group. There was no evidence that GM CSF was associated with a greater incidence of leukaemic relapse. PMID- 1878736 TI - Serum erythropoietin levels in allogeneic, non T-depleted bone marrow transplantation, and the effects of rhEpo administration. PMID- 1878737 TI - How do allogeneic bone marrow transplants cure leukaemia? The role of graft versus host disease. PMID- 1878738 TI - The role of BMT for neuroblastoma relapse patients. A report of the EBMT-STR. PMID- 1878739 TI - Single or double consolidation treatment according to remission status after initial therapy in metastatic neuroblastoma: first results of LMCE 3 study in 40 patients. PMID- 1878740 TI - Unpurged ABMT for neuroblastoma: AIEOP-BMT experience. PMID- 1878741 TI - A single center experience with bone marrow transplantation for high risk neuroblastoma. PMID- 1878742 TI - The effects of probucol on the progression of atherosclerosis in mature Watanabe heritable hyperlipidaemic rabbits. AB - 1. Probucol was administered to mature Watanabe heritable hyperlipidaemic (WHHL) rabbits (approximately 9 months old). Groups of WHHL rabbits were randomly selected and treated as follows: Group 1 killed at 9 months (n = 9); Group II placed on sham-treated diet at 9 months and followed for 6 months (n = 8); Group III placed on probucol at 9 months and followed for 6 months (n = 8). Probucol was administered by mixing 1% wt/wt drug with standard laboratory diet. 2. Plasma concentrations of probucol increased to 93 +/- 11 micrograms ml-1 in Group III during the initial 2 weeks and increased further to 149 +/- 24 micrograms ml-1 at the end of the treatment period. 3. Plasma concentrations of total cholesterol, unesterified cholesterol and phospholipids were significantly reduced overall by probucol, while triglycerides were not affected. 4. No statistically significant differences were observed in the presence of oxidized products in low density lipoproteins (LDL) isolated from plasma of controls compared to probucol-treated rabbits. However, LDL from probucol-treated animals was resistant to oxidation in the presence of Cu2+ (3 microM). 5. Group I had aortic atherosclerosis covering 70 +/- 5% of intimal area of thoracic aortae, that increased to 91 +/- 3% in Group II. This was associated with cholesterol contents of aortae increasing from 1.4 +/- 0.2 microgram mg-1 in Group I to 2.7 +/- 0.3 microgram mg-1 in Group II. Probucol administration did not produce a statistically significant reduction of atherosclerotic lesion area (78 +/- 7%). However, probucol treatment reduced cholesterol content to 1.9 + 0.3,ugmg-' (P < 0.01). Collagen content of aortae was not affected by probucol treatment. 6. Thus, while probucol did not promote regression, the drug did retard the continued deposition of cholesterol esters into atherosclerotic lesions of mature WHHL rabbits. PMID- 1878743 TI - The diverse effects of cromakalim on tension and 86Rb efflux in canine arterial smooth muscle. AB - 1. To characterize further the K+ channels opened by cromakalim in arterial smooth muscle, the effects of cromakalim on tension and 86Rb efflux were compared in endothelium-denuded strips of coronary, mesenteric and middle cerebral (MC) arteries of the dog. 2. Cromakalim relaxed strips precontracted with 20.9 mM K+. The maximum relaxation induced by cromakalim varied in the arteries used; 94% in the coronary artery, 60% in the mesenteric artery and only 38% in the MC artery. Cromakalim failed to relax arterial strips precontracted with 65.9 mM K+. 3. When the effects of cromakalim on 86Rb efflux were determined in 20.9 mM K(+) contracted strips, cromakalim-induced relaxations were accompanied by a large increase in 86Rb efflux in the coronary artery, by a small increase in the mesenteric artery but by an apparent decrease in the MC artery. 4. When 10(-7) M nifedipine was added to 20.9 mM K(+)-contracted strips, to inactivate Ca2(+) activated K+ (KCa) channels, cromakalim produced a greater increase (measured from the point at which cromakalim was administered) in 86Rb efflux than in the absence of nifedipine, suggesting that the effects of cromakalim on 86Rb efflux from the 20.9 mM K(+)-contracted strips may be the resultant of two opposing effects: an increased 86Rb efflux perhaps due to the opening of ATP-sensitive K+ (KATP) channels, and a decreased efflux due to the closing of KCa channels. 5. After the inactivation of Kca channels in 20.9mM K+-contracted strips, the cromakalim-induced increase in 86Rb efflux measured as area under the curve was eight times greater in the coronary artery than in the MC artery. The increase in 86Rb efflux in the mesenteric artery was intermediate between these extremes. 6. Cromakalim also increased the 86Rb efflux from 65.9 mm K+-contracted strips. This increase was not augmented by the addition of nifedipine. Under these conditions, a similar variation in efflux response (as area under the curve) for cromakalim was noted in the arteries used. 7. The relaxant responses of each artery to cromakalim were competitively antagonized by glibenclamide, a blocker of KATP channels. The cromakalim-induced increase in 86Rb efflux was also inhibited by glibenclamide. 8. These results suggest that cromakalim-opened K+ channels in the three arteries may differ in terms of their frequency of occurrence in the plasmalemma, their permeability to 86Rb and their ability to modulate tension development. On the other hand, the activities of Kca and voltage-sensitive K+ channels, estimated from the effects of nifedipine, were similar in the three arteries. PMID- 1878744 TI - P2 purinoceptor regulation of mucin release by airway goblet cells in primary culture. AB - 1. The effects of adenine analogues on mucin release by airway goblet cells have been examined in a hamster primary tracheal epithelial cell culture. 2. Adenosine, a P1 receptor agonist, had no effect on mucin release even at 2 mM, while ATP, a P2 receptor agonist, stimulated mucin release in a dose-dependent fashion with an apparent EC50 of 20 microM. The relative potency order among adenine nucleotides was ATP greater than ADP greater than AMP = adenosine. 3. ATP gamma S, a non-hydrolyzable analogue of ATP, was equipotent with ATP in stimulating mucin release. The potency order among some ATP analogues was ATP greater than 2-methylthio ATP greater than alpha, beta-methylene ATP greater than beta, gamma-methylene ATP. Reactive blue 2, a putative P2 gamma-purinoceptor antagonist, did not block the ATP-induced mucin release. 4. The present results indicate that mucin release by airway goblet cells is stimulated by extracellular ATP via P2 receptor-mediated mechanism. We suggest that this mechanism may be important in the physiological regulation of airway goblet cell mucin release in vivo. PMID- 1878746 TI - Investigation into the 5-hydroxytryptamine receptor mediating smooth muscle relaxation in the rat oesophagus. AB - 1. An investigation has been made into the 5-hydroxytryptamine (5-HT) receptor mediating relaxation of rat oesophagus in preparations precontracted with carbachol. 2. In tissues treated with pargyline (100 microM) and in the presence of corticosterone (30 microM) and cocaine (30 microM) the potency of 5-HT and 5 methoxytyramine (5-MeOT) was not changed but the maximum response to these agonists was reduced. Thus there was no evidence of metabolism and/or uptake through an amine depleting mechanism. 3. The relaxant concentration-effect curves to 5-HT were shifted to the left in a concentration-related manner by isobutylmethylxanthine (1 and 10 microM), suggesting the involvement of adenosine 3':5'-cyclic monophosphate in these responses. 4. 5-HT produced concentration related relaxations of rat oesophagus with an EC50 value of 0.24 microM. Several indole agonists were tested and the following rank order of potency of key agonists obtained: 5-HT greater than alpha-methyl-5-hydroxytryptamine = 5 carboxamidotryptamine (5-CT) greater than 5-MeOT. In contrast, 2-methyl-5 hydroxytryptamine, sumatriptan and 8-hydroxy-2-(di-n-propylamino) tetralin were weak or inactive. 5. The substituted benzamides, metoclopramide, cisapride, renzapride and R,S-zacopride acted as partial agonists, producing 60-70% of the 5 HT maximum. 6. The relaxation responses to 5-HT were neither inhibited by antagonists selective for 5-HT1 or 5-HT2 receptors nor by the 5-HT3 receptor antagonists, ondansetron, granisetron or MDL 72222. 7. The relaxation responses induced by 5-HT, 5-CT, 5-MeOT and renzapride were selectively inhibited by high concentrations of ICS 205-930 with pKB values of approximately 6. 8. The 5-HT receptor mediating relaxation in rat oesophagus cannot be designated 5-HT1, 5-HT2 or 5-HT3 under the current 5-HT classification, but the observed effects are consistent with stimulation of the putative 5-HT4 receptor. PMID- 1878745 TI - Pulse exposure to protein synthesis inhibitors enhances vascular responses to des Arg9-bradykinin: possible role of interleukin-1. AB - 1. The modulation of the spontaneous increase in contractile responses to des Arg9-bradykinin (des-Arg9-BK) of rabbit aortic strips incubated in vitro was studied. Rapid hypotensive responses to exogenous kinins were also measured in rabbits anaesthetized 5 h following pretreatment. 2. Continuous exposure to the protein synthesis inhibitors cycloheximide (71 microM) or anisomycin (3.8 microM) profoundly inhibited the sensitization to des-Arg9-BK in incubated aortic strips. However, temporary (3 h) inhibition of protein synthesis in vitro followed by further incubation (3 h) of tissues without inhibitor, paradoxically enhanced both the maximal contractile responses to des-Arg9-BK (1.7 microM) and the apparent affinity of the kinin without affecting contractions to noradrenaline (NA, 100 nM) at 6.5 h. 3. The stimulatory activity of the short treatment (pulse) with cycloheximide was abolished in the presence of dexamethasone sodium phosphate (100 microM throughout the incubation). The function of receptors for kinins did not appear to be altered directly by the steroid treatment. 4. Interleukin-1 beta (IL-1 beta), applied at low concentrations (100-250 pg ml-1) on aortic strips between 3 h and 6.5 h of incubation time, mimicked the selective stimulatory effect of the cycloheximide pulse on responses to des-Arg9-BK. Higher concentrations of IL-1 beta (0.5-5 ng ml-1) did not further amplify the responses to des-Arg9-BK but decreased the contractile responses to NA. 5. The modulation by IL-1 beta of vascular sensitivity to des-Arg9-BK and to NA was prevented by blockade of protein synthesis. 6. The induction in vivo by IL-1 beta (5 micrograms kg-1) or by cycloheximide (10 mg kg-1) of cardiovascular responsiveness to des-Arg9-BK was demonstrated with a blood pressure assay of exogenous kinins or with tissues isolated ex vivo 5 h after pretreatment of animals. Evidence of active disposition of cycloheximide in vivo was also obtained. 7. We propose the production of endogenous IL-1 as a possible mechanism for the enhancement of responsiveness to des-Arg9-BK observed in tissues pulsed with a protein synthesis inhibitor and for the inducing effect of cycloheximide or E. coli lipopolysaccharide in vivo. These results suggest that effects mediated by the BK1 receptor for kinins are potentially present in pathological conditions associated with IL-1 production. PMID- 1878747 TI - The role of endogenous thromboxane in contractions to U46619, oxygen, 5-HT and 5 CT in the human isolated umbilical artery. AB - 1. The effects of selective thromboxane antagonists and a thromboxane synthase inhibitor on the contraction to 9,11-dideoxy-11 alpha,9 alpha-epoxymethano prostaglandin F2 alpha (U46619) and oxygen in the human umbilical artery (HUA) were examined. The effect of the antagonists on contractions to both 5 hydroxytryptamine (5-HT) and 5-carboxamidotryptamine (5-CT) were also examined. 2. U46619 (0.3 nM-10 microM) contracted the HUA. This contraction was antagonized by two selective thromboxane receptor antagonists EP092 (10 nM-1 microM) and GR32191B (10 nM-1 microM). The contraction was not affected by the selective thromboxane synthase inhibitor, dazoxiben (10 nM-1 microM). 3. When the oxygen tension was increased from 16 mmHg to 120 mmHg, the HUA transiently contracted. Both thromboxane antagonists inhibited this contraction in a concentration dependent manner with 1 microM almost completely abolishing the response (the oxygen-induced contraction of the control preparation normally increases with a second exposure to 120 mmHg oxygen). 4. In low (16 mmHg) oxygen, responses to both 5-HT and 5-CT were unaffected by both thromboxane receptor antagonists at concentrations up to 1 microM. In high oxygen (120 mmHg) responses to both 5-HT and 5-CT were biphasic in nature, with an additional initial high sensitivity phase, which was abolished by a cyclo-oxygenase inhibitor. In high oxygen, EP092 and GR32191B blocked this initial phase in a concentration-dependent manner, returning sensitivity to 5-HT and 5-CT to that seen in low oxygen. 5. The thromboxane synthase inhibitor, dazoxiben, at concentrations greater than 10 nm inhibited the contraction to 120 mmHg oxygen and at 1 microM, dazoxiben almost abolished the response. In low oxygen, the response to 5-HT was unaffected by dazoxiben at concentrations up to 10 microM. In high oxygen, the initial phase of the contraction to 5-HT was inhibited by concentrations greater than 10 nm, with no effect on the maximum response. 6. The results show that thromboxane receptor antagonism or blockade of thromboxane synthesis selectively attenuates oxygen induced contractions and those responses to 5-HT and 5-CT which are dependent on high oxygen for their expression. This suggests that the contractions caused by high oxygen tension, and the enhancement of the contractile effects of low concentrations of 5-HT and 5-CT in the presence of high oxygen tension are mediated by endogenously released thromboxane A2. PMID- 1878748 TI - Adenosine-induced dilatation of the rabbit hepatic arterial bed is mediated by A2 purinoceptors. AB - 1. This study was carried out in order to identify the receptor responsible for adenosine-induced dilatation of the hepatic arterial vascular bed. 2. Livers of 10 New Zealand White rabbits were perfused in vitro with Krebs-Bulbring buffer via the hepatic artery and the portal vein at constant flows of 26 and 77 ml min 1 100 g-1 liver respectively. The tone of the preparation was raised by the presence of noradrenaline in the perfusate (concentration: 10(-5) M). 3. Dose response curves for adenosine and its analogues 5'-N-ethyl-carboxamido-adenosine (NECA), the 2-substituted NECA analogue CGS 21680C, and R- and S-N6-phenyl isopropyl-adenosine (R- and S-PIA) were obtained after their injection into the hepatic arterial supply. 4. The order of vasodilator potency of these agents was: NECA greater than CGS 21680C greater than adenosine greater than R-PIA greater than S-PIA. Their potency, expressed relative to that of adenosine, was in the approximate ratio 10:3:1:0.3:0.1, consistent with that resulting from activation of P1-purinoceptors of the A2 sub-type (which mediate vasodilatation due to adenosine). 5. The P1-purinoceptor antagonist 8-phenyltheophylline (10(-5) M) caused significant attenuation of the vasodilatation to adenosine and analogues. 6. It is concluded that adenosine-induced dilatation of the hepatic arterial vascular bed is mediated by P1-purinoceptors of the A2 sub-type. PMID- 1878749 TI - Characterization of P2X- and P2Y-purinoceptors in the rabbit hepatic arterial vasculature. AB - 1. Responses to adenosine 5'-triphosphate (ATP) and its agonists were studied in the isolated liver of the rabbit dually perfused through the hepatic artery and the portal vein. 2. In the hepatic arterial vascular bed at basal tone, ATP and its agonists elicited vasoconstrictor responses with the rank order of potency alpha,beta-methylene ATP greater than 2-methylthio ATP greater than ATP, consistent with their action at the P2X-purinoceptor. 3. When tone was raised with noradrenaline (10(-5) M), vasodilator responses were produced with ATP and 2 methylthio ATP; alpha,beta-methylene ATP produced only further constriction. The rank order of vasodilator potency was 2-methylthio ATP greater than ATP much greater than alpha,beta-methylene ATP, consistent with their action at the P2Y purinoceptor. 4. Methylene blue (10(-5) M) antagonized vasodilator responses to acetylcholine and ATP, but not those to adenosine or sodium nitroprusside. Addition of 8-phenyltheophylline (10(-5) M) antagonized responses to adenosine but not those to sodium nitroprusside. Responses to ATP remaining after antagonism with methylene blue were not further antagonized by 8 phenyltheophylline. 5. These results present evidence for discrete P2X- and P2Y purinoceptors in the rabbit hepatic arterial bed which mediate vasoconstrictor and vasodilator responses respectively. 6. Vasodilatation produced by ATP was entirely due to direct action at the P2Y-purinoceptor, and not at a P1 purinoceptor following breakdown to adenosine. The antagonism of these responses by methylene blue is consistent with the view that vasodilatation by ATP takes place largely via endothelial P2Y-purinoceptors that lead to release of endothelium-derived relaxing factor. However, we cannot exclude the possibility that P2y-purinoceptors located on the vascular smooth muscle play a contributory role in ATP-induced vasodilatation. PMID- 1878750 TI - Endothelins: vasoconstrictor effects and localization in canine cerebral arteries. AB - 1. The vascular effects of endothelin and localization of endothelin-like immunoreactivity were characterized in isolated cerebral arteries of dogs. 2. Endothelin-like immunoreactivity was detected in a few populations of endothelial cells of dog basilar artery. 3. Endothelin-1, endothelin-2 and endothelin-3 contracted isolated ring preparations of cerebral arteries in a dose-dependent manner independently of the presence of endothelium. The ED50 values (and 95% confidence intervals) for the contraction were 411 pM (242-697 pM) and 478 pM (295-776 pM) for endothelin-1 and endothelin-2, respectively. Endothelin-3 induced vascular contraction at a higher concentration (ED50 = 26.5 nM, 95% confidence interval = 15.7-45.7 nM). 4. The increases in tone induced by endothelin-1 and endothelin-2 did not return to the resting level after repeated washings, while a rinse with Krebs solution reversed the vasoconstrictor response to endothelin-3. The endothelins did not cause any vasodilator response in arteries precontracted with uridine 5'-triphosphate even in the presence of intact endothelial cells. 5. NiCl2 (1 mM) attenuated the contractions induced by endothelin-3 (10-300 nM) and those to relatively low doses (1 nM) but not higher doses (10-100 nM) of endothelin-1 and endothelin-2. The contractions in response to endothelin-1, endothelin-2 and endothelin-3 were greatly attenuated in Ca(2+) free solutions although high concentrations of endothelin-1 and endothelin-2 still evoked contractions. 6. These results suggest that the vasoconstriction induced by endothelin-3 and lower doses of endothelin-1 and endothelin-2, largely depends on the influx of Ca2+ ions. The apparent insensitivity to Ni2+ shows that additional distinct mechanisms also operate in the vasconstrictor responses to high concentrations of endothelin-1 and endothelin-2. 7. The presence of endothelin-like immunoreactivity in endothelial cells suggests that endothelin is a potential endogenous spasmogen. PMID- 1878751 TI - Rapid decrease in neuropeptide Y gene expression in rat adrenal gland induced by the alpha 2-adrenoceptor agonist, clonidine. AB - 1 The mechanism of regulation of the neuropeptide Y (NPY) gene by pharmacological treatment with the alpha 2-adrenenoceptor agonist, clonidine, was investigated by quantitative Northern blot analysis of the effects of this drug on the NPY mRNA levels in rat adrenal gland and medulla oblongata/pons. 2 In the adrenal gland, clonidine-treatment (50 microgram kg-1, s.c., once daily) resulted in decrease in the amount of NPY mRNA to 44 +/- 10% of the control level in 24 h and then its increase to 162 +/- 16% of the control level after 5 days. Concomitant changes in putative NPY pre-mRNA species (7.0 and 3.3 kb) were observed, probably due to changes at the level of NPY gene transcription. 3 The short-term (24 h) effect of clonidine was blocked by yohimbine (5 mg kg-1, i.p., once daily). Yohimbine alone tended to increase the NPY mRNA level after 24h. 4 The recovery/increase in the NPY mRNA level in the adrenal gland after 5 days treatment with clonidine was similar to its increase after treatment with reserpine (0.5 mg kg-1, i.p., once daily). 5 NPY gene expression in the medulla oblongata/pons was not changed by short- or long-term treatment with clonidine. 6 These results suggest that clonidine suppresses NPY gene expression in the adrenal gland, probably at the level of transcription, by activation of the alpha 2-adrenoceptor. PMID- 1878752 TI - Comparison of the effects of the K(+)-channel openers cromakalim and minoxidil sulphate on vascular smooth muscle. AB - 1 The actions of the potassium channel openers, cromakalim and minoxidil sulphate, were compared in a range of isolated blood vessel preparations. 2 Cromakalim and minoxidil sulphate inhibited spontaneous mechanical activity of the guinea-pig portal vein and relaxed the noradrenaline precontracted rat aorta with similar potency. In contrast, minoxidil sulphate was less potent than cromakalim in inhibiting spontaneous activity in the rat portal vein and was essentially inactive in the noradrenaline precontracted rat mesenteric artery and rabbit aorta. 3 Minoxidil sulphate did not antagonize the effects of cromakalim in the rabbit aorta indicating it was not acting as a partial 'agonist'. 4 Charybdotoxin, noxiustoxin and rubidium failed to discriminate between cromakalim and minoxidil sulphate indicating that the apparently selective effects of minoxidil sulphate were not mediated by either Ca(2+)-activated potassium channels, delayed rectifiers or rubidium impermeable potassium channels. 5 Glibenclamide antagonized the effects of cromakalim in an apparently competitive manner whereas the effects of minoxidil sulphate were antagonized in a non competitive manner. The involvement of subtypes of ATP-sensitive potassium channels is discussed. PMID- 1878753 TI - Modulation by the epithelium of the extent of bronchial narrowing produced by substances perfused through the lumen. AB - 1 Airway narrowing was determined in vitro as a measure of bronchial reactivity. A bronchial segment from pig lung was perfused with a Krebs solution and the change in flow rate to drugs and small ions perfused intraluminally was compared with that obtained by application to the serosal surface. 2 The sensitivity (EC50) to acetylchloline was 30 times greater on the serosal surface than on the luminal surface. Concentrations of histamine and carbachol which had threshold responses on flow rate when perfused intraluminally virtually stopped flow on the serosal surface. Potassium depolarizing solutions (containing either KCl or K2SO4) and vanadate (VO3-) had little or no effect intraluminally but completely stopped flow through the bronchial segment when applied to the serosal surface, i.e. they closed off the airway. 3 After removal of the epithelium the sensitivity to drugs and K+ perfused intraluminally was increased to equal that on the serosal surface. 4 No evidence for suppression of smooth muscle contraction by a putative epithelium-derived inhibitory factor (EpDIF) could be obtained: no inhibition of smooth muscle contractility was seen when the agents listed above were perfused intraluminally and their perfusion continued while they were applied to outside. 5 It was concluded that the epithelium plays a crucial role as an impermeant barrier in modulating the responsiveness of the airways smooth muscle. PMID- 1878754 TI - Evidence for prejunctional inhibitory muscarinic receptors on sympathetic nerves innervating guinea-pig trachealis muscle. AB - 1 Relaxation responses induced by stimulation of the postganglionic sympathetic nerve trunk were studied in the isolated, fluid-filled, innervated tracheal tube preparation of the guinea-pig. 2 The thromboxane-mimetic U46619, prostaglandin F2 alpha and histamine each caused concentration-dependent increases in the intraluminal pressure (ILP) of the fluid-filled tracheal tube, reflecting contraction of the trachealis muscle. Sympathetic nerve stimulation in the presence of the spasmogens caused relaxations which increased with increasing ILP. Relaxant responses evoked in the presence of these three spasmogens were comparable at any given ILP. 3 Muscarinic agonists caused concentration-dependent increases in ILP, pilocarpine being more potent than acetylcholine. Sympathetic nerve-induced relaxations were reduced in the presence of pilocarpine and acetylcholine when compared to those obtained at the same ILP in the presence of U46619. This inhibitory effect of muscarinic agonists on sympathetic nerve induced responses was concentration-dependent. 4 Exogenously applied noradrenaline opposed the contractile effect of U46619 and acetylcholine to a similar extent, indicating that a comparable degree of postjunctional functional antagonism exists between the sympathetic neurotransmitter noradrenaline and both spasmogens. 5 The selective M2 muscarinic antagonists, gallamine and methoctramine, altered neither the postjunctional contractile action of acetylcholine nor its inhibitory effect on sympathetic nerve-induced relaxations. In addition, the inhibitory effect of acetylcholine was not modified by concentrations of pirenzepine known to block M1 muscarinic receptors. 6 The postjunctional contractile action of acetylcholine and its inhibitory effect on sympathetic neuro-transmission were antagonized by atropine, by the M3 muscarinic antagonist hexahydrosiladiphenidol and by higher concentration of pirenzepine. 7. These results suggest that in the guinea-pig trachea, muscarinic cholinoreceptor agonists inhibit sympathetic neurotransmission via activation of muscarinic receptors located on the sympathetic nerve endings. These inhibitory prejunctional muscarinic heteroreceptors are of the M3 subtype. PMID- 1878755 TI - The effect of E. coli STa enterotoxin on the absorption of weakly dissociable anti-malarial drugs from rat intestine in vivo. AB - 1. The effect of E. coli heat stable (STa) enterotoxin on the absorption of radiolabelled anti-malarial weak bases and their appearance in peripheral blood was assessed in vivo by a recirculation procedure in rat intestinal loops. 2. Enterotoxin increased the jejunal disappearance of quinine (P less than 0.05), trimethoprim (P less than 0.05), proguanil (P less than 0.05) and chloroquine (P less than 0.001) and left pyrimethamine disappearance unaltered. Peripheral blood levels of trimethoprim (P less than 0.02) and proguanil (P less than 0.05) were higher after STa exposure. 3. In the ileum, enterotoxin increased the luminal disappearance (P less than 0.05) and peripheral blood appearance (P less than 0.001) of chloroquine. The luminal disappearance rate of trimethoprim was reduced (P less than 0.05) and that of pyrimethamine unchanged. 4. The increased jejunal absorption of the anti-malarial drugs occurred despite STa causing a reduction in the amount of net fluid absorption. It seems likely that the enhanced absorption with STa exposure is related to the effect of STa on the microclimate pH. An elevation in the microclimate pH would increase the amount of undissociated weak base available for non-ionic diffusion. 5. The favourable elevation of microclimate pH by STa seemed to be outweighted by the reduced fluid absorption in the ileum. Only chloroquine still showed enhanced absorption in the ileum and this may have been because unlike the other antimalarial drugs, chloroquine has two dissociable groups likely to be affected by the mucosal surface pH changes. PMID- 1878756 TI - Short-term effects of administration of anticonvulsant drugs on free carnitine and acylcarnitine in mouse serum and tissues. AB - 1. The short-term evolution of concentrations of free carnitine and acylcarnitine was studied in the serum, liver, kidney, heart and skeletal muscle of mice after administration of single therapeutic doses of the anticonvulsant drugs, valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT) and phenobarbitone (PHB). 2. The effects of the drugs were immediate but transitory, control levels of free carnitine and acylcarnitine having been recovered or almost recovered in serum and in all tissues 8 h post administration (p.a.). 3. VPA was the only drug that significantly reduced free carnitine concentration in serum, which recovered control levels by 4 h p.a. 4. All the drugs studied brought about marked deficits of serum acylcarnitine, which had disappeared 2 h p.a. in the case of VPA and not until 8 h p.a. for CBZ, PHT or PHB. 5. The minimum concentrations of free carnitine and acylcarnitine in serum were invariably associated with the maximum concentration of drug in serum. 6. Free carnitine concentration was not affected by VPA in any tissue, PHT and PHB brought about significant deficits in heart and kidney, and CBZ a significant deficit in muscle. 7. Acylcarnitine concentration was significantly reduced in heart, kidney and muscle by CBZ, PHT and PHB, but in liver the effects of all drugs were very small. 8. These results are compatible with the hypothesis that the primary cause of anticonvulsant-induced alteration of carnitine metabolism is interference with renal reabsorption of carnitine. PMID- 1878757 TI - An electrophysiological study of the actions of angiotensin II at the sympathetic neuroeffector junction in the guinea-pig vas deferens. AB - 1. The effects of angiotensin II on sympathetic neuroeffector transmission in the guinea-pig vas deferens have been investigated by the use of intracellular and focal extracellular recording techniques to measure indirectly, the release of adenosine 5'-triphosphate (ATP). 2. Angiotensin II (10-100 nM) did not alter the amplitude of the first excitatory junction potential (e.j.p.) in a train but increased the amplitude of subsequent e.j.ps. There was a corresponding increase in the probability of occurrence of extracellularly recorded evoked excitatory junction currents (e.j.cs). Spontaneous quantal transmitter release was unaffected by angiotensin II. 3. The enhancement of transmitter release produced by angiotensin II was prevented by the angiotensin receptor antagonist, saralasin. 4. The increase in transmitter release produced by angiotensin II was due to an increase in the probability of transmitter release from individual varicosities and not due to any detectable change in the configuration of the nerve terminal impulse or to the induction of repetitive firing. 5. There was no overall enhancement of e.j.ps or e.j.cs by angiotensin II in reserpinized tissues. Surprisingly, the predominant effect of angiotensin II in reserpinized vasa deferentia was to inhibit evoked transmitter release, an effect reversed by indomethacin (3 microM). 6. The results show that angiotensin II increases the release of sympathetic transmitter by activating prejunctional angiotensin II receptors. However, when the co-transmitter noradrenaline was depleted, angiotensin II now inhibited transmitter release indirectly, presumably by stimulating prostaglandin formation in the smooth muscle cells which then inhibited release transjunctionally. PMID- 1878758 TI - Characterization of endogenous noradrenaline release from intact and epithelium denuded rat isolated trachea. AB - 1. Overflow of endogenous noradrenaline (NA) from the in vitro incubated rat trachea evoked by two periods of electrical field stimulation (S1, S2 at 3 or 15 Hz) or by high potassium (60 mM) was determined by high performance liquid chromatography (h.p.l.c.) with electrochemical detection. 2. In the presence of the neuronal uptake inhibitor desipramine, the alpha 2-adrenoceptor antagonist, yohimbine, enhanced the overflow of NA evoked by stimulation at 3 Hz by about 100% suggesting the presence of presynaptic inhibitory autoreceptors on the sympathetic nerves innervating the trachea. 3. When desipramine and yohimbine were present throughout the experiments, the overflow of NA evoked by the second period of electrical stimulation (S2) was significantly smaller than that evoked by the first (S1). This decline of overflow was prevented when the NA precursor, tyrosine, was additionally present throughout the experiments. 4. After removal of the epithelium, the tissue content of NA was reduced by about 30%, suggesting that part of the NA may be present and released within the epithelium. However, the overflow of NA evoked by stimulation at 3 Hz or 15 Hz was reduced by 70-80%, indicating that the epithelium may additionally exert a permissive role on the release of NA within the airways, possibly by suppressing inhibitory factors. 5. Stimulation by high potassium (60 mM for 10 min) caused a large overflow of NA (about 45% of the tissue NA), both from epithelium-free and epithelium-denuded tracheae. Thus the 'endogenous inhibition' of NA release after removal of the epithelium is surmountable when a high potassium stimulus is applied. PMID- 1878759 TI - Effects of pretreatment with caffeine or ryanodine on the myocardial response to simulated ischaemia. AB - 1. The cytoplasmic calcium concentration ([Ca]c) of rat isolated atrial myocardium was assessed with the dye indo-1. Dye-loaded atria were superfused with physiological salt solution and excited with radiation at 360 nm, while epifluorescence emissions were collected simultaneously at 400 nm and 500 nm. The ratio of these emissions was used as a measure of [Ca]c. 2. Dye-loaded atria showed a phasic rise and fall in [Ca]c with each applied electrical pacing stimulus. The amplitude of these oscillations was reduced by the presence of caffeine (10(-3)-10(-2) M) or of ryanodine (10(-8)-10(-6) M) in a concentration dependent manner. 3. Atria superfused with a solution the composition of which resembled that found extracellularly in regions of myocardial ischaemia rapidly lost systolic increments in [Ca]c, while end-diastolic [Ca]c values gradually rose. 4. Pretreatment with caffeine (10(-2) M) or ryanodine (10(-7) M) protected atria against the rise in end-diastolic [Ca]c that occurred when the tissue was exposed to conditions of simulated ischaemia. PMID- 1878760 TI - Haemodynamic effects of human alpha-calcitonin gene-related peptide following administration of endothelin-1 or NG-nitro-L-arginine methyl ester in conscious rats. AB - 1 We investigated the peripheral haemodynamic effects of human alpha-calcitonin gene-related peptide (CGRP) following administration of endothelin-1 or NG-nitro L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide production, in conscious, chronically-instrumented, Long Evans rats. 2 Infusion of endothelin-1 (3 nmol kg-1 h-1) caused hypertension, bradycardia and renal, mesenteric and hindquarters vasoconstrictions. Co-infusion of human alpha-CGRP (1.5 nmol kg-1 h 1) reduced the hypertension and abolished the hindquarters vasoconstriction caused by endothelin-1 but the renal and mesenteric vasoconstrictor actions of endothelin-1 were not affected. 3 Infusion of human alpha-CGRP (15 nmol kg-1 h-1) in the presence of endothelin-1 caused hypotension and hyperaemic vasodilatation in the hindquarters; the mesenteric vasoconstrictor effects of endothelin-1 were diminished, but there was only a transient reversal of the renal vasoconstrictor effects of endothelin-1. 4 Pretreatment with the non-peptide angiotensin II receptor antagonist, DuP 753 (10 mg kg-1), caused slight hypotension associated with renal, mesenteric and hindquarters vasodilatations, but DuP 753 did not affect responses to endothelin-1 infusion. However, under these conditions co infusion of human alpha-CGRP (15 nmol kg-1 h-1) caused a sustained reversal of the renal vasoconstrictor effects of endothelin-1. 5 These results indicate that the failure of human alpha-CGRP to cause sustained reversal of the renal vasoconstrictor effects of endothelin-1 in the absence of DuP 753 was due to activation of the reninangiotensin system (possibly as a consequence of the hypotension). 6. In the second experiment, L-NAME (l0mgkg-1) caused renal, mesenteric and hindquarters vasoconstrictions similar to those seen in the presence of endothelin-1. However, the renal vasoconstrictor effects of L-NAME were reversed completely by human alpha-CGRP (l5nmolkg- h-1), even though the latter caused hypotension comparable to that seen in the presence of endothelin 1. These results are consistent with a lack of functional activation of the renin angiotensin system by human alpha-CGRP in the presence of L-NAME. 7. The vasoconstrictor effects of L-NAME on the hindquarters were completely reversed by infusion of human alpha-CGRP, but hindquarters flow and vascular conductance did not rise above baseline levels. Hence these results indicate the hindquarters hyperaemic vasodilator effects of human alpha-CGRP seen in the presence of endothelin-1 were contributed to by nitric oxide-mediated mechanisms. PMID- 1878761 TI - Effect of capsaicin on PAF-induced bronchial hyperresponsiveness and pulmonary cell accumulation in the rabbit. AB - 1 Platelet activating factor (PAF), but not the carrier molecule bovine serum albumin (BSA) induced bronchoconstriction in the anaesthetized rabbit. This bronchoconstriction was not altered by prior treatment with capsaicin. 2 Rabbits demonstrated increased airways responsiveness to histamine 24h after exposure to PAF but not to BSA. PAF failed to increase airways responsiveness to histamine in animals pretreated with capsaicin (80 mg kg-1). 3 A significant increase in inflammatory cells was obtained in bronchoalveolar lavage (BAL) 24h after PAF exposure in vehicle-treated rabitts. This was associated with an increase in the numbers of neutrophils and eosinophils. Capsaicin treatment inhibited the PAF induced influx of inflammatory cells found in BAL, although this was not associated with an inhibition of PAF-induced pulmonary eosinophilia. 4 Capsaicin induced motor effects were modest in epithelium-intact rabbit bronchial preparations, but were significantly enhanced in epithelium-denuded preparations in the presence of thiorphan. The contractile response to capsaicin was significantly inhibited in tissues exposed to a consecutive dose of capsaicin. Furthermore, ruthenium red abolished capsaicin-induced contraction in epithelium denuded preparations. 5 Tissue content of calcitonin gene-related peptide-like immunoreactivity and substance P-like immunoreactivity was not reduced in bronchus and iris obtained from capsaicin-treated rabbits, although capsaicin induced contractile responses in rabbit bronchus obtained from animals previously treated with capsaicin were significantly reduced. Furthermore, airway responses to histamine, methacholine and electrical field stimulation in vitro, were not altered by pretreatment of rabbits in vivo for 3 days with capsaicin. 6. In conclusion, PAF-induced airways responsiveness and pulmonary cell accumulation is inhibited by in vivo capsaicin pretreatment in the rabbit, via a mechanism that may not involve depletion of sensory neuropeptides. PMID- 1878762 TI - Stereoselective effects of the enantiomers of bupivacaine on the electrophysiological properties of the guinea-pig papillary muscle. AB - 1 Direct myocardial effects of the S(-)- and R(+)-enantiomers of bupivacaine were compared in the guinea-pig isolated papillary muscle by recording transmembrane action potentials with the standard microelectrode technique. 2 In 5.4 mM K+, at a stimulation rate of 1 Hz, the maximal rate of depolarization (Vmax) was reduced to 59.9 +/- 1.4% (n = 10) of control (mean +/- s.e.mean) in the presence of 10 microM R(+)-bupivacaine, and to 76.7 +/- 1.2% (n = 14) in the presence of the same concentration of S(-)-bupivacaine. This was mainly due to a difference in time constant at which block dissipated during the diastolic period. Recovery was slower in the presence of R(+)-bupivacaine. The slower recovery in the presence of R(+)-bupivacaine resulted also in a more pronounced frequency-dependent block of Vmax. 3 Time constants for recovery from use-dependent block became significantly faster for both enantiomers on hyperpolarization, while no significant change was observed at depolarization. At all membrane potentials recovery was slower in the presence of R(+)-bupivacaine. 4 The action potential duration (APD) was shortened to a greater extent in the presence of R(+) bupivacaine over a large range of stimulation frequencies. 5 We conclude that S( )-bupivacaine affects Vmax and APD in the guinea-pig papillary muscle less than the R(+)-enantiomer at different rates of stimulation and resting membrane potentials. PMID- 1878763 TI - Social images of suicide. AB - Emile Durkheim's analysis of historical attitudes of societies toward suicide led him to claim that (1) the social disapproval of suicidal conduct increased constantly from ancient times to the present; (2) such increased disapproval was generated by the growing emphasis put on the dignity and sacredness of the individual; (3) the condemnation of suicidal conduct was therefore essentially moral, and it expressed the strong reaction of the collective conscience against offenses to the cult of the individual. In this study we show that Durkheim's interpretation of the historical evidence is erroneous: not increasing condemnation of suicide, but rather tolerance or mild aversion is the typical social response to suicide. Also, when confronted with the historical evidence, Durkheim's claim that increased disapproval of suicide accompanied increased consideration for the dignity of the individual is shown to be unfounded. Our argument develops in four steps. First, we survey the historical evidence on views of suicidal conduct from classical times to the nineteenth-century; second, we present the moral statistics literature on suicide which flourished during Durkheim's lifetime; third, we analyze Durkheim's own theory of anomic suicide. In the conclusion we propose an alternative interpretation of the historical evidence on attitudes on suicide, and a different framework in which to highlight their significance in contemporary society. PMID- 1878764 TI - The effects upon helping behaviour of wearing pro-gay identification. AB - Shoppers were approached either by an ostensibly pro-gay person, wearing a tee shirt bearing a pro-gay slogan, or by a person wearing an unmarked tee-shirt, asking for change of a pound. Help was less likely to be given to the ostensibly pro-gay person. This effect was not attenuated when the request was justified by a socially acceptable reason for needing change (although, overall, help was more likely to be given when requests were so justified). There were no effects of the sex of the subject or the sex of the person asking for change; nor were there any interactions involving those variables. The results suggest that the negative attitudes towards homosexuals reported in other studies have clear behavioural correlates and that 'homophobia' may be widespread in the general population. PMID- 1878765 TI - The representation of self in multidimensional cognitive space. AB - A number of studies point to the efficiency with which people process self relevant trait information. The derivative models of self-cognition account for many judgement latency and memory effects. These models tend to limit themselves, however, by neglecting the cognitive representation of the traits themselves. In contrast, research on implicit personality theory has focused on the cognitive representation of trait information, but has not always addressed the relationship between self and the judged traits. These two research domains were linked in an effort to specify the cognitive representation of self. A method for locating individuals and traits within the same spatial representation was developed and validated in two studies. In Study 1, subjects exhibited superior recall for traits located closest to self. In Study 2, subjects rapidly selected which of two traits better or least described self. 'Better' judgements were faster with increasing closeness to self of selected traits whereas 'least' judgements were faster with increasing closeness to self of non-selected traits, supporting the view of self as fixed anchor in self-relevant decision making. Taken as a whole, these two studies provided further evidence for the self as an evaluative organization of knowledge. PMID- 1878766 TI - Growth rates and patterns of organs and tissues in the bovine fetus. AB - Ninety-two purebred Jersey fetuses from clinically normal dams derived from a variety of sources but unexposed to experimental infection, were killed between 80 and 260 days after conception and dissected to provide basic parameters of a normal population. Organs and tissues were weighed and measured and the equations for the regression of the values on fetal age evaluated. Growth followed a sigmoid curve with rapid changes in growth rate between 140 and 170 days' gestation. While a few variables increased their growth rate over the late fetal period, the majority maintained a low even rate of growth. Thyroid and cerebellum weights showed a marked reduction in growth rate at this time. Long bone length and crown-anus length were the most predictable parameters for a given gestational age. PMID- 1878767 TI - Disposition of tylosin in goats. AB - The disposition kinetics of tylosin was studied in goats after intravenous (i.v.) or intramuscular (i.m.) injection of 15 mg/kg body wt. Following i.v. injection, tylosin was rapidly and widely distributed with a distribution half-life of 0.2 h and volume of distribution of 1.7 l/kg. It was slowly eliminated with a mean elimination half-life of 3.04 h and a total body clearance rate of 6.8 ml/kg/min. Following i.m. injection, tylosin was slowly absorbed (tau 1/2 ab of 1.82 h). Tylosin concentration in serum was greater than 1 microgram/ml after 1 h and persisted up to 12 h post-injection. The peak concentration (Cmax 2.38 micrograms/ml) was obtained after 4.19 h. The systemic bioavailability of tylosin injected intramuscularly was 72.6% and the serum protein bound fraction was 37.59% of the total drug. Tylosin was excreted in milk and urine at concentrations much higher than that in serum. Low concentrations of tylosin were reported in ruminal juice of goats. In conclusion tylosin should be injected every 14 h to obtain an appreciable concentration in serum, milk and urine. PMID- 1878768 TI - The microflora of the lower respiratory tract of the horse: an autopsy study. AB - A series of 31 thoroughbreds and 18 non-thoroughbreds was examined post mortem to assess what bacteria might be present in the lower respiratory tract, and to assess their significance by correlating the bacteriological findings with histological changes in the lung. The distal trachea and seven representative lung sites were swabbed in each case. Sixty-six per cent of the sites were sterile with remaining sites producing scanty growths of mainly coagulase negative Staphylococcus spp., E. coli, Bacillus spp. and Pseudomonas spp. Anaerobes, mainly Clostridium perfringens, Bacteroides fragilis and Bacteroides oralis, were only recovered on enrichment media and were isolated more frequently from the right lung than the left. More bacterial species were isolated from thoroughbreds than non-thoroughbreds. Significant inflammation was absent in the majority of lungs examined and this correlated well with the large percentage of sterile sites and low number of potential pathogens. The results indicate that the lower respiratory tract of horses is normally sterile or may contain small numbers of bacteria of low pathogenicity. Chlamydia and respiratory viruses were not isolated from any horse. PMID- 1878769 TI - Pyaemia in pigs. AB - Pyaemia is by far the most important cause of condemnation in pigs slaughtered in Singapore abattoirs. Between 1983 and 1987, 1757 from a total of 4,899,731 pigs were condemned by meat inspectors for pyaemia, accounting for 0.036% of the total condemnations. The common post-mortem findings of affected pigs during the 5-year period are presented. Abscesses were most commonly seen in the liver (22%), spleen (21%), gastrohepatic lymph node (20%) and bronchial lymph node (17%). Pseudomonas pseudomallei was the most predominant organism isolated, accounting for 39% of the pyaemic cases. The public health significance of abscesses in pigs is discussed with particular reference to melioidosis. PMID- 1878770 TI - Effect of electrical stunning on somatosensory evoked responses in the turkey's brain. AB - The effects of head only or waterbath electrical stunning on somatosensory evoked responses in the brain of turkeys were examined. When head only stunning with a sinusoidal AC of 50 Hz was followed within 15 s by neck cutting the evoked responses were absent following the stun. When neck cutting was not performed, the evoked responses returned from 30 s after the stun. When currents between 120 and 250 mA were used in a waterbath stunner some birds retained their evoked responses immediately after the current was applied. The proportion of birds that retained their responses after the stun was not related to the level of the current that was applied. PMID- 1878771 TI - The production performance of imported Friesian cattle under heavy Trypanosoma challenge in a rain forest zone of Nigeria. AB - The productivity of 76 newly imported pregnant Friesian cattle and two bulls under heavy trypanosome challenge in the rain forest belt of Nigeria is reported. At the first visit in August 1989 and within 7 months of arrival of the heifers, the herd population had reduced by 26 (33.3%) as a result of deaths (six animals) and culls/salvages (20). The surviving 52 animals were generally in poor health with classical symptoms of trypanosomiasis. Thirty-one (40.8%) of the pregnancies were unsuccessful because of abortions (13 animals), premature births (seven), embryonic deaths (five) and death of heifers (six). Of the 45 successful calvings, 16 perinatal deaths occurred. All serum samples were negative for brucellosis. Only 41 (63.1%) of the 65 productive heifers lactated of which 24 (58.5%) yielded milk only for 6 months and less. The remaining 17 (41.5%) heifers were still at different stages of lactation ranging from 3 to 7 months within the period of analysis. Treatment with isometamidium (Samorin) at 0.5 mg/kg body weight cured the infection and prevented reinfections and/or relapses within 3 months of administration. A rise in the haematocrit and milk production after Samorin treatment was recorded. Careful analysis of the outbreak indicated that the reproductive wastages and poor lactational performance may have been induced by the severe trypanosomiasis diagnosed in the herd. PMID- 1878772 TI - Radiographic investigation of dystocia in the West African dwarf goat. AB - Lateral and ventrodorsal radiographs were obtained from 30 West African dwarf goats with dystocia. The pelvic size was estimated from the ventrodorsal radiographs as the product of the transverse and conjugate diameters of the pelvic inlet. Radiography clearly showed the number of fetuses present, their presentation and position. The posture was clearly defined in singletons but not in twins and triplets. The commonest abnormal fetal disposition was bilateral flexion of the forelimbs with the head in the pelvic canal. The major maternal abnormality was small pelvic area. Of 19 dead fetuses, 13 showed radiographic signs of intrauterine death including free intracavity gas, tissue emphysema, abnormal fetal disposition and overlapping cranial bones. It was concluded that radiography is useful during examination of goats with dystocia especially small sized goats that cannot be manipulated easily. PMID- 1878773 TI - An abattoir survey of female genital disorders of imported camels (Camelus dromedarius) in Kano, Nigeria. AB - An abattoir survey of 850 female genital organs of imported camels was conducted at the Kano abattoir between October 1987 and April 1988. An incidence of 4.49% of disorders was recorded, including follicular cystic degeneration (0.12%), ovarian haemorrhagic cysts (0.47%), pyometra (0.35%), early embryonic mortality (0.12%), endometrial haemorrhages (0.47%), fetal maceration (0.12%), abscess (0.24%), vulvar tick infestation (1.77%) and cervical hypoplasia (0.12%). PMID- 1878774 TI - Number and distribution of retinal ganglion cells in anubis baboons (Papio anubis). AB - The number of retinal ganglion cells in Papio anubis was determined from light microscopic observations of wholemounted and vertically sectioned retinal tissue and electron microscopic examination of optic nerve cross sections. The total number of ganglion cells ranged from 1.41 to 1.81 million (mean 1.58 million, n = 6, SD = 169,927) per retina. The distribution of ganglion cells in cresyl violet stained wholemounts was also examined. Isodensity contours were almost circular perifoveally, but became horizontally elongated outside of the central retina, providing strong evidence for a visual streak. Ganglion cell somata within the streak were found to be significantly smaller than those outside of the streak in comparing regions of equal density. Finally, the distribution of blood vessels within the retina formed a watershed pattern with its crux centered on the ridge of this horizontally oriented high-density zone. Combined, these features indicate that anubis baboons possess a visual streak specialization as reported for lagomorphs, felines, and several primate species. Further, the visual streak appears more pronounced in anubis baboons than in any other primate species studied to date, with the possible exception of Homo sapiens, a similarly ground dwelling/foraging and secondarily terrestrial species. PMID- 1878775 TI - Inter- and intrasexual dimorphisms in the vocal control system of a teleost fish: motor axon number and size. AB - In one species of vocalizing fish, the plainfin midshipman (Porichthys notatus), large, nest-guarding males ('type I') use striated muscles to produce acoustic communication signals that include short duration (less than 1 s) 'burps' important in agonistic encounters and long duration (in the order of minutes) 'hums' which function in attracting females to nest sites during the breeding season. Females, and a second group of smaller reproductively active males ('type II') that 'sneak' spawn, do not generate hums, although they produce burps. Differences in vocal behavior are paralled by a relative increase of 6-fold in the sonic muscle of type I males. Inter- and intrasexual dimorphisms in sonic muscle mass were matched by those in the cross-sectional area of sonic motor axons, but not by those in number of axons. Thus, axon size was 2- to 3-fold larger in type I males than in females, type II males, or juveniles, none of which differed significantly from each other. Axon number was similar between type I males and females of a similar body size, despite the extreme dimorphism in sonic muscle mass. Axon number, however, was slightly greater (0.1-fold) in type I males and females compared to the smaller-sized juveniles and type II males. Type II males, in comparison to the non-reproductive juvenile males, have gonads that are about 20-fold larger and produce mature sperm. Nevertheless, the two groups resemble each other in body and swimbladder size, as well as sonic motor axon size and number. This suggests that type II males represent a subset of juvenile males that undergo precocious gonadal hypertrophy and spermiogenesis, but retain juvenile-like nongonadal traits. The results are discussed within the context of the development of vertebrate motor systems as well as the evolution of alternative reproductive tactics among teleost fishes. PMID- 1878776 TI - A brain atlas of the northern fulmar (Fulmarus glacialis) in stereotaxic coordinates. AB - The brain of a procellariiform bird, the Northern Fulmar (Fulmarus glacialis), is presented in the form of a stereotaxic atlas. The Northern Fulmar is especially interesting because both field and laboratory evidence support olfaction as one of its major sensory systems. The nasal cavity and olfactory bulb of most procellariiforms are among the largest of all avian orders; the central olfactory pathways may be more extensive as well. A brain atlas of the Northern Fulmar, a relatively accessible procellariiform species on which several studies have already been done, can provide reference for research both on neural mechanisms underlying olfaction and on comparative neuroanatomical data within Aves and between avian and nonavian groups. PMID- 1878777 TI - Read but not write "idea": evidence for a third reading mechanism. AB - Most information processing accounts of reading incorporate either two or three mechanisms by which oral reading may be accomplished. The existence of a "third" mechanism by which words may be read lexically but without semantic mediation remains controversial. We report data from a patient (W.T.) with an infarction involving Wernicke's area who was unable to write, repeat, or comprehend words of low imageability yet read these and other words reliably; the patient could not, however, read nonwords. As the patient was unable to read on the basis of sublexical print-to-sound correspondences and, at least for words of low image ability, was unable to read by means of a semantically mediated process, the data from this patient are most readily accommodated by models of reading incorporating three mechanisms. PMID- 1878778 TI - Understanding of relational time terms before and after in Parkinsonian patients. AB - The role of the relational time terms before and after in language comprehension was investigated using patients with Parkinson's disease (PD) and normal controls (NC) in Greek. Results lead to the following four conclusions: (a) Comprehension by PD patients of before and after constructions displaying syntactic, semantic, and cognitive constraints equivalent to those of English is significantly different from that of NC matched on chronological age, sex, education, and socioeconomic status. (b) Before is better understood than after. (c) Syntactic variables, when semantic effects are partialed out, do not affect performance. The same is true of semantic effects when syntactic variables are partialed out. (d) Order of mention of events is a predominant source of errors when syntax and semantics are controlled. The data are discussed in relation both to findings with aphasics and to developmental results on the same time terms. PMID- 1878779 TI - Aphemia after a penetrating brain wound: a case study. AB - The speech of a patient with aphemia (pure anarthria) resulting from a penetrating brain wound was studied using linguistic and acoustic observations as well as electromyographic recordings from four labial muscles. The results are discussed in relation to phonetic disintegration's syndrome and apraxia of speech which, respectively, enhance linguistic disorders and motor programming disturbance. PMID- 1878780 TI - Word identification in isolation and in context by college dyslexic students. AB - College dyslexic students (DYS) were compared to chronological age (CA)-matched and to reading age (RA)-matched control groups on tasks assessing naming of words and nonwords, regular and irregular words, and the use of context in word identification. The DYS group had the slowest naming latency for words in all tasks. In addition, they had extreme difficulty in naming nonwords, which in terms of the dual-route model for word recognition indicates impairment in the indirect route to the lexicon. However, they displayed a regularity effect in reading regular and irregular words and thus apparently utilized the indirect route in reading words. Correlational data supported the conclusion that the data are in conflict with the traditional dual-route model, and an alternative conceptualization is suggested. The use of context is discussed in terms of the interactive-compensatory model (Stanovich, 1980) and findings were generally supportive of the model. The DYS subjects of the present study appeared to be different from the RA controls and their performance did not support a developmental-lag model for explaining their reading problems. PMID- 1878781 TI - Early lexical development in children with focal brain injury. AB - Early lexical development in 27 children with focal brain injury was studied cross-sectionally and longitudinally. Data were obtained from children between 12 and 35 months of age who acquired their lesion prenatally or within the first 6 months of life. Results for the group as a whole provide clear evidence for delays in lexical comprehension and production, and for a larger number of comprehension/production dissociations than would be expected by chance. In addition, a significant number of children were observed having unusual difficulty mastering predication and/or using an atypically high proportion of closed class words (suggesting reliance on holistic/formulaic speech). Analyses by lesion type revealed no effect of lesion size. Analyses according to side of lesion revealed that children with right-hemisphere damage produced a higher proportion of closed class words, suggesting heavy reliance on well-practiced but under-analyzed speech formulae. Children with left-hemisphere damage were slightly better in comprehension than children with right-hemisphere damage. In addition, left posterior lesions were associated with greater delays in expressive language, and delays were more protracted in children with left posterior damage. No differential effects of left posterior damage were found for lexical comprehension. PMID- 1878782 TI - Evolution of chemotherapy. PMID- 1878783 TI - Cancer chemotherapeutic and biologic agents. PMID- 1878784 TI - The American Cancer Society Guidelines for the cancer-related checkup: an update. PMID- 1878785 TI - The role of the pathologist in the management of breast cancer. AB - The pathologist is a consultant in breast cancer management whose responsibility is to establish the histologic diagnosis of cancer as well as its anatomic extent once sufficient tissue has been provided. The consultation also provides data that may be used to aid in selecting primary or adjuvant therapy, evaluating new therapies, estimating prognosis, and assessing outcome. Examples of such data are the TNM histopathologic classification of the anatomic extent of the cancer used for the stage grouping (T = the extent of the primary tumor, N = the absence or presence and extent of regional lymph node metastasis, and M = the absence or presence of distant metastasis); tumor size, histologic type, and histologic and/or nuclear grade; assessment of blood vessel and lymphatic vessel invasion; analysis of steroid receptors, and other special studies as appropriate. PMID- 1878786 TI - The process of metastasis. PMID- 1878787 TI - The relationship between circumcision and cancer of the penis. PMID- 1878788 TI - Questionable cancer practices in Tijuana and other Mexican border clinics. AB - Tijuana, Mexico, has become a refuge for cancer patients who have been convinced that they may be cured of their terminal illness by unconventional, unproved, and disproved methods offered in the border clinics. About a dozen United States promoters have joined with Mexican colleagues to offer a variety of treatments. Some patients are diagnosed using standard methods prior to arrival at the clinics, but many healthy individuals are misdiagnosed as having cancer or "precancer" and are then treated there. Others are told they have been cured or are improving even though they still have active disease. The modalities and regimens used are often referred to as "metabolic therapy" and, for the most part, are either not based on sound scientific principles or have been shown in controlled clinical trials to be useless or even dangerous. A basic metabolic regimen consists of three phases: detoxification with fasting and bowel cleansing, strengthening the immune system with numerous "supplements," and attacking cancer with "natural and non-toxic" chemicals. Popular treatments include injections of hydrogen peroxide, large quantities of pressed liver and carrot juice, coffee enemas, infusions of Laetrile mixed with massive doses of vitamins and dimethylsulfoxide (DMSO), special diets, and a host of other pseudoscientific regimens. Unfortunately, no evidence exists that any of these modalities is more effective than no treatment at all. Patients traveling to the Mexican border clinics for metabolic therapy are subjecting themselves to costly and hazardous regimens, especially if they forgo responsible medical care in the process. The American Cancer Society, therefore, strongly urges individuals with cancer not to seek treatment with metabolic therapies in the Mexican border clinics. PMID- 1878789 TI - Teaching of behavioural sciences: Nuffield ten years on. PMID- 1878790 TI - The prevalence of enamel mottling on incisor teeth in optimal fluoride and low fluoride communities in England. AB - The prevalence of enamel mottling in optimal and low fluoride areas of the West Midlands was studied in March 1989 using the Al-Alousi index and the TF index. A total of 600 children aged 8-10 years, in three groups of 200 each, formed the study group. Significantly more mottling was found in the optimal fluoride area, according to both indices, although the TF index demonstrated the difference more clearly. Social class had no effect upon the prevalence of mottling in the optimal fluoride area. PMID- 1878791 TI - Reasons given for tooth extraction in Hong Kong. AB - Two hundred and seventy dentists, systematically selected from the membership lists of the Hong Kong Dental Association, were sent forms on which they were invited to record the reasons for tooth extraction in all patients aged 16 years and above over a period of five to six weeks. Third molars were excluded. Fifty five per cent of the recording sheets dispatched were returned with usable data. Data were provided on 8516 extractions performed for 6331 patients. Overall caries was the reason given for 60 per cent of extractions; periodontal disease for 28 per cent; prosthetic indications for six per cent; trauma (which included tooth wear) for four per cent; and orthodontic and other reasons for two per cent. Extractions for periodontal reasons were more common in those aged 40 years and above, but periodontal disease did not exceed caries as a reason for extraction even in those aged 60 years and over. The tooth type most frequently extracted was the first molar. Mandibular incisors were the teeth most commonly extracted for periodontal reasons. In this community, which has benefited from water fluoridation since 1961, caries was the dominant reason given by dentists for tooth extractions in all age groups of the subjects studied. PMID- 1878792 TI - Deprivation and dental health. The benefits of a child dental health campaign in relation to deprivation as estimated by the uptake of free meals at school. AB - The objectives of the present study were to evaluate the overall effect of the 1989 Lothian dental health education campaign on 8-year-old school children's dental health knowledge and behaviour and to examine the relationship between free meals and the children's benefit from the campaign. Altogether 874 children were randomly selected and included in the study. Sugar-free meals and drinks were provided in all primary schools throughout the campaign week. Dental officers held 30-minute information sessions with each class and encouraged teachers to continue dental health activities. Dental knowledge and behaviour were evaluated by interviews immediately before and after the campaign. The results showed a significant increase in knowledge about diet and dental health and a significantly higher proportion of children claimed to choose non cariogenic foods and drinks as a result of the campaign. Toothbrushing frequency also increased significantly. Ninety-eight per cent of the children enjoyed the campaign and 66 per cent discussed it with their family. Each school was classified according to the proportion of children receiving free school meals, and this showed a statistically significant negative correlation with the proportion of children who chose non-cariogenic meals and drinks before the campaign but not afterwards. Toothbrushing frequency showed a significant negative correlation with free meals both before and after the campaign. A positive correlation was found between free meals and the proportion of children who claimed to have received new information during the campaign and ate healthier food because of it.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878793 TI - Oral hygiene practices, oral cleanliness and periodontal treatment needs in 12 year old urban and rural school children in Ghana. AB - The aim of the present study was to inquire into oral cleaning practices, and to determine levels of oral cleanliness and periodontal treatment need among 12-year old Ghanaian school children living in urban and rural areas. Of the 985 children examined, 38 per cent claimed to use a toothbrush, 31 per cent chewing sticks, 17 per cent plantain and 14 per cent the chewing sponge. In rural areas, traditional methods were preferred, and only 8 per cent used a toothbrush. On examination, oral debris was present in 84 per cent of the sample, and more than three quarters had calculus deposits. Children in urban areas, and particularly those attending private schools, had the cleanest mouths and the lowest periodontal treatment need. Multiple regression analysis showed that the social class background of the child, which reflects motivation and awareness for good oral health, was the most significant predictor for levels of oral cleanliness and CPITN, whereas the method or frequency of cleaning employed were not significant variables. PMID- 1878794 TI - Dental caries and dental attendance patterns in Vietnamese children aged 11-12 years resident in three inner London boroughs, UK. AB - Ninety-one Vietnamese children aged 11-12 years were examined in schools in Lambeth, Lewisham and Southwark. Their dental caries prevalence and attendance for dental care were compared with 464 Caucasians, Negroes and Asians. Vietnamese children had a greater caries experience than all except Asians. Although most caries was treated, over a third of Vietnamese children were symptomatic attenders. PMID- 1878795 TI - Caries susceptibility of first permanent molars and treatment needs in Sri Lankan children, aged 13-16 years, in 1986. AB - The caries status of the permanent first molar was studied in 683 school children (aged 13-16 years) selected from six schools in Kandy. Radike (1972) criteria were used for the examination. Of 2732 first molars examined, 37 per cent were found to be carious, filled or missing. Susceptibility to caries was higher in mandibular molars (47 per cent) than in maxillary molars (25 per cent). In 36 per cent of the children all four molars were sound, while in 11 per cent they were all affected by caries. Of 998 DMF units, 676 (68 per cent) were decayed, 189 (19 per cent) filled and 133 (13 per cent) extracted. Seventy-nine per cent of the DF sites were occlusal. Results suggest that a high proportion of carious permanent molars have been neglected without the seeking of professional care. Approaches for preventive and restorative care for the permanent first molar tooth, appropriate in Third World countries, are suggested. PMID- 1878796 TI - Quality assurance. A project on patient waiting times at appointment in an orthodontic department. AB - A quality assurance project to establish patient waiting time at appointments was undertaken over a four-week period during the spring of 1989. The Orthodontic Department was selected as one of two departments in the Birmingham General Hospital/Birmingham Dental Hospital unit site that was to participate in the programme initiated at the District Health Authority management level. Patient waiting periods for a total of 142 clinical sessions were assessed. Fifty per cent of patients were kept waiting and 50 per cent were seen either earlier or at their appointed time. The mean period of time that patients were kept waiting past their appointment time was 9.4 min (+/- 10.9). On clinics for which patients arrived late the mean time that they were kept waiting increased to a mean of 18.9 min (+/- 9.1). Data from 92 patient questionnaires established that they considered a reasonable mean time of waiting to be 16.1 min (+/- 7.9). Five recommendations were proposed as a result of this quality assurance initiative and their implementation is discussed. PMID- 1878797 TI - Evaluation of a postal reminder system for the attendance of patients. PMID- 1878798 TI - The research experience: from Agassiz to the Victoria embankment. PMID- 1878799 TI - "If preventable why not prevented?". PMID- 1878800 TI - The dental caries experience of 5-year-old children in Great Britain. A survey coordinated by the British Association for the Study of Community Dentistry in 1989-90. PMID- 1878801 TI - [The clinical observation and follow-up of acute rheumatic fever]. AB - There were 15 patients under 15 years of age with cases of acute rheumatic fever diagnosed by revised Jones criteria admitted to pediatric department, Chang Gung Memorial Hospital of Kaohsiung from Jan. 1986 through Dec. 1989. There were 11 boys and 4 girls. The age of onset was more commonly between 13 and 15 years old. Carditis was the most common clinical presentation, noted in 13 cases. Eleven cases had valvular involvement: mitral regurgitation (MR) and mitral valve prolapse (MVP), 5 cases; MR and aortic regurgitation (AR), 4 cases; MR, 1 case; and MVP, 1 case. One case with MR + AR also suffered transient acute glomerulonephritis, which presented with gross hematuria but improved one week later. And one case with severe MR expired due to severe congestive heart failure. Eleven of the 14 survivors had regular follow-up at our clinic with an interval of 3 months to 38 months, and received parenteral benzathine penicillin for prophylaxis. During follow-up, the murmur in 4 cases with MR + MVP and 2 cases with MR + AR disappeared within 2 months. One of the three cases who had not received secondary prophylaxis had recurrence of rheumatic fever 3 years later after the initial diagnosis. PMID- 1878802 TI - [Pilomatricoma-a clinicopathological analysis of 22 cases, including 2 cases of bullous pilomatricoma]. AB - Twenty-two patients with pilomatricoma seen from January 1986 to October 1990 were analyzed retrospectively. The incidence of pilomatricoma in our dermatopathologic material is 1 in every 50 cases of skin tumors. Male to female ratio is 1:2. Half of the tumors appeared before the age of 30. Most of the tumors develop in the head, neck and upper extremities. Two pilomatricomas appeared with overlying bullae. Pathologically, multiple dilated lymphatics in the dermis were found above the typical nests of shadow cells and basophilic cells. Clues to clinical diagnosis are summarized below. The stony hard, deep seated tumor, covered by normal skin, is usually located in the upper extremity. Tumors with blue-red discoloration, firm or elastic, frequently found in eyelid and face, are located more superficially, clinically they should be differentiated from epidermal cysts. Erythematous protruding tumors occur in the scalp or face. Bullous pilomatricoma is characteristically manifested as a flaccid, thick-walled bulla with an underlying palpable hard nodule, usually seen in the shoulder, upper arm or the head. PMID- 1878803 TI - [Emergency obstetric hysterectomy: report of fifteen cases]. AB - From June 1978 to June 1990, there were 41,989 deliveries, 13,396 cesarean sections and 15 emergency obstetric hysterectomies at Taipei Chang Gung Memorial Hospital. The incidence of emergency obstetric hysterectomy is 36/100,000 deliveries. The mean age of patients is 31.7 years old. The indications for hysterectomy were placental disorder (60.0%), uterine atony (26.7%), and uterine rupture (13.3%). The present series showed that 14 cases had total abdominal hysterectomy, while only one case had a subtotal hysterectomy. Total hysterectomy should generally be performed unless maternal instability mandates a more expeditious subtotal hysterectomy. The most common postoperative complication included unknown fever and urinary tract infection. For those four cases of post cesarean hysterectomy, conservative treatment was tried but failed. All cases presented with hypotension (less than 80/60 mmHg), tachycardia (greater than 100 times/min) and with a mean hemoglobin of 9 mg% during the observation period. In these patients, blood loss, operating time and length of hospitalization was increased when compared with a group of 7 patients undergoing cesarean hysterectomy. In patients with placenta accreta, who are candidates for cesarean hysterectomy, initial hypotension, tachycardia and shock developed during cesarean section. It must be emphasized that conservative aggressive measures to control obstetric hemorrhage remain the mainstay of therapy, but emergency hysterectomy played the life-saving role with which every practitioner of obstetrics must be familiar and keep in mind. PMID- 1878804 TI - [Usage of antidepressants in public hospitals in 1984 and 1986 fiscal years in Taiwan]. AB - Prescription of psychotropic medications, especially anxiolytics and antidepressants, has been increasing steadily since the late 60's. From the survey conducted in the developed countries, prescription of psychotropic medications by nonpsychiatric physicians in general hospitals and private practices has significantly increased. This study analysed the usage of antidepressants in public hospitals in 1984 and 1986 fiscal years as reported by Department of Health, the Executive Yuan. The amount of antidepressants increased from 1,928,585 tablets to 2,348,281 tablets, an increase of 21.8%. The total cost increased from 6,052,732 N.T. $ to 7,488,374 N.T. $, an increase of 23.8%. The amount of antidepressants used ranked between 2 common G-I drugs, Biscodyl (Dulcolax) and Cimetidine. PMID- 1878805 TI - A comparison of CT and MR images in migration disorders of brain. Report of four cases. AB - Migration disorders are congenital brain malformations. These anomalies may be overlooked in CT studies. We present four cases with migration disorders. All have both CT and MRI studies. Comparison of the images of CT and MRI at corresponding levels is demonstrated. The superiority of MR images to CT in delineating the migration and sulcation disorders is discussed. PMID- 1878806 TI - Transferring the location of a parasagittal lesion in CT to the scalp. Report of two cases. AB - By referring to the curve connecting the parietal eminences across the vertex, it is possible to transfer the location of a parasagittal lesion in the computed tomography (CT) scans to the scalp. The successful use of this new technique in 2 patients is reported. PMID- 1878807 TI - Dedifferentiated chondrosarcoma arising from osteochondromatosis. A case report. AB - Multiple hereditary osteochondromata has a higher incidence (5%-25%) of malignant change into chondrosarcoma than solitary osteochondroma (1%-2%); but only less than 10% of all chondrosarcomas may undergo dedifferentiated change into fibrosarcoma or malignant fibrous histiocytoma. We have a case presented here with osteochondromatosis who was found to have dedifferentiated chondrosarcoma arising from pelvic osteochondroma. Radical extra-compartmental resection was done and followed by chemotherapy and radiotherapy. Recurrence was found 3 months later. Early recognition of malignant change and adequate surgical resection with adjuvant therapy may prevent local recurrence and increase the survival rate. PMID- 1878808 TI - [Neonatal adrenal hemorrhage. A case report]. AB - Neonatal adrenal hemorrhage is frequently associated with large fetal size, birth trauma owing to difficult labor or delivery, perinatal asphyxia, fetal hypoxia, septicemia or coagulation defect. A case of giant baby with perinatal asphyxia and birth injury complicated with adrenal hemorrhage is presented. The baby was admitted at five days of life due to profound jaundice. Right adrenal hematoma was found by abdominal sonography. The hematoma resolved gradually under supportive management by three months of age as documented by serial sonography. No complication was found. We conclude that abdominal sonography is the modality of choice for initial diagnosis and follow-up of neonatal adrenal hemorrhage, and conservative management is the mainstay of treatment. PMID- 1878809 TI - Effects of endogenous and exogenous hyperglycemia on renal glucose transport in the rat. AB - As acute renal glucose loading requires intravenous infusion of a large quantity of hypertonic glucose solution, we performed free-flow micropuncture studies in nine streptozotocin diabetic rats to evaluate renal tubule glucose transport in hyperglycemic state and the results were compared with those of 10 normal rats in which comparable hyperglycemia was induced by exogenous glucose loading. Despite hyperglycemia with a mean plasma glucose concentration at 19.2 mmol/l, glomerulotubular balance in the proximal tubule of the diabetic rats was well maintained with a mean proximal tubule fluid-to-plasma inulin ratio at 2.08 +/- 0.15 as compared with that of the normal control at 2.16 +/- 0.11. Acute glucose loading in the normal rats raised plasma glucose to a similar mean of 19.6 mmol/l, significantly inhibited proximal fluid and glucose reabsorption, increased their reabsorption in the intermediate segment (between late proximal tubule and early distal tubule) and led to natriuresis and exaggerated glycosuria (fractional sodium excretion 1.32% and fractional glucose excretion 14.8% compared with 0.47% and 7.3%, respectively, for the diabetic control). Administration of insulin to normalize plasma glucose in the diabetic rats also inhibited proximal fluid and glucose reabsorption and resulted in modest natriuresis. This observation is consistent with the existence of sodium-glucose cotransport in the proximal tubule with sodium transport being reduced along with glucose transport following insulin administration. It is concluded that acute glucose loading, as performed in the conventional glucose titration study, leads to artifactual inhibition of proximal sodium and glucose transport. PMID- 1878810 TI - Changing trends of forceps delivery in Chang Gung Memorial Hospital. AB - Two hundred and fifty-five patients underwent forceps deliveries in Chang Gung Memorial Hospital from January 1, 1985 to June 30, 1990. There was neither maternal nor perinatal mortality related to this procedure during this period; and the perinatal outcome was good without sequela. In the past three years, cesarean section took the place of forceps delivery in some cases with acute fetal distress and malposition. As a result, maternal problems became the most common indication for forceps delivery during that period. Fourth degree laceration of the perineum was the major maternal complication, occurring in 22.4% of total forceps deliveries. Postpartum voiding problems continued to be another complication after forceps delivery, accounting for 7.0%. Either fourth degree laceration of the perineum or postpartum voiding difficulty could be prevented to a certain extent if the forceps were handled delicately in an experienced hand and there was early diagnosis with prompt management of voiding dysfunction. PMID- 1878811 TI - Preliminary experience with growth factor and porcine graft-young collagenous wettable membrane in the treatment of chronic diabetic ulcer. AB - Chronic ulcers are well-known complication of diabetes mellitus, often compounded by infection. Healing of lesions is problematic in some cases using conventional treatment. We have treated a group of six hospitalized diabetic patients with chronic ulcer by a combined regimen consisting of metabolic control, parenteral antibiotics, growth factor and porcine graft-young collagenous wettable membrane (YCWM) treatment. Five of our uncontrolled group had their ulcers improved at 87 +/- 37.6 hospital days after 45.8 +/- 20.2 days of growth factor and YCWM treatment. In conclusion, growth factor and porcine graft-YCWM therapy may be promising as an alternative choice in treatment of chronic diabetic ulcer. PMID- 1878812 TI - [Pseudomembranous colitis: a clinical analysis and review of literatures]. AB - Clostridium difficile has been well known to be a pathogen of pseudomembranous colitis. It is characterized by the formation of elevated plaques and pseudomembranes which result in varying degree of diarrhea. This series analysed 20 cases of pseudomembranous colitis diagnosed at Chang Gung Memorial Hospital between January 1985 and December 1989. The male to female ratio was 1:3. Their ages ranged between 13 and 81 years, with a mean of 53.7 years. Sixteen of our patients claimed to have taken antibiotics for upper respiratory tract infection, pneumonia, cellulitis or acute pelvic inflammatory disease within six weeks before onset of symptoms. The antibiotics were mainly in the penicillin group and cephalosporin group. Clinical presentations included diarrhea of varying degree, fever, and abdominal pain. The diagnosis was made by the typical colonic mucosal changes under sigmoidoscopic or colonoscopic examination and pathological findings. The lesions were prominent in the rectum and sigmoid colon. Eleven cases were treated with vancomycin. Of these, one failed and died, and two recurred. The two recurrences were again treated with the same dose of vancomycin and with complete remission. Three of our patients responded to metronidazole. The other six cases with milder symptoms were successfully controlled by using cholestyramine (2 cases) or by supportive treatment (4 cases). PMID- 1878813 TI - Manitoba virus, a new rhabdovirus isolated from Culex tarsalis mosquitoes collected in Manitoba, Canada. AB - A rhabdovirus, Mn 936-77, was isolated from a pool of two Culex tarsalis collected on August 16, 1977, from Morris, Manitoba. Isolate Mn 936-77 was not pathogenic for suckling Swiss white mice inoculated by the intracerebral route. The virus propagated in three vertebrate cell lines (Vero, primary chick embryo, mouse neuroblastoma), but apparently not in Aedes albopictus C6/36 cells. Isolate Mn 936-77 did not react by amplified enzyme-linked immunosorbant assay with 230 viruses of proven or possible arbovirus etiology or by immunofluorescence with 88 members of the family Rhabdoviridae. Isolate Mn 936-77 appears to be a newly discovered virus for which the name Manitoba virus is proposed. PMID- 1878814 TI - Evidence of peroxisomes and peroxisomal enzyme activities in the oleaginous yeast Apiotrichum curvatum. AB - The presence of peroxisomes and peroxisomal enzyme activities were investigated in the oleaginous yeast Apiotrichum curvatum ATCC 20509 (formerly Candida curvata D.) Catalase, a marker enzyme for peroxisomes, was measured in cell-free extracts prepared by sonication. The nature of the carbon and nitrogen sources in the growth medium greatly affected catalase activity. Cells grown on corn oil had high specific activity of catalase, but those grown on glucose, sucrose, or maltose had low specific activity. High specific activity of catalase was measured in cultures grown on media that supported poor growth (with soluble starch as carbon source or with methylamine, urea, or asparagine as nitrogen source). Peroxisomes from cells grown on corn oil were separated from other subcellular fractions in a discontinuous sucrose gradient. Major peaks of activity of fatty acid beta-oxidation and of two key enzymes in the glyoxylate cycle were found in fractions containing peroxisomes, but not in fractions corresponding to the mitochondria. Peroxisomal beta-oxidation showed equivalent activity with palmitoyl CoA or n-octanoyl CoA as substrate. Mitochondria did not seem to contain NAD-linked glutamate dehydrogenase. Peroxisomes with a homogeneous matrix and core surrounded by a single-layer membrane were observed with an electron microscope in cells grown on corn oil, but not in those grown on glucose. Staining with 3,3'-diaminobenzidine revealed that catalase activity was located in peroxisomes. Peroxisomes in this oleaginous yeast play important roles in lipid metabolism. PMID- 1878815 TI - The stability of outer-membrane protein and antigen profiles of a strain of Bacteroides intermedius grown in continuous culture at different pH and growth rates. AB - The stability of the outer-membrane proteins and antigens of a strain of Bacteroides intermedius (VPI 8944 group genotype II) grown in continuous culture at varying pH and growth rates (D = 0.025-0.2 h-1, pH 6.0-7.3) has been measured. The membranes showed nine major proteins (greater than 67-19.55 kilodaltons) and six major antigens (65-28 kilodaltons). Membrane proteins and antigens were stable under the conditions tested; the major proteins were detected in all membranes, and the antigen profiles tested with different antisera showed maximum similarities of 82-95%. Differences did occur in the amounts of membrane proteins synthesized; cells at high growth rates and those growing on the surfaces in the chemostat showed increased amounts of two proteins (40 and 32 kilodaltons) and possibly novel proteins of 24 and 25 kilodaltons. In addition, these membranes reflected increased synthesis or a change to increased reactivity of antigens between 20.5 and 24 kilodaltons. The results indicate stability of the expression of outer-membrane proteins and antigens in environments of differing pH and under different growth rates. However, the amount of these molecules synthesized can vary, and increases in certain proteins and antigens occur as the growth rate increases and the organisms grow on surfaces. PMID- 1878816 TI - Cleavage of proteins of reproductive secretions by extracellular proteinases of Tritrichomonas foetus. AB - Cleavage of host defense proteins from reproductive secretions was investigated as a potential virulence mechanism for Tritrichomonas foetus extracellular proteinases. Three categories of susceptibility to digestion were found among the defense proteins tested. Cleavage of fibrinogen, fibronectin, and albumin occurred rapidly with more than 50% of these digested within 30 min. Lactoferrin, immunoglobulin G1, and immunoglobulin G2 were more than 50% digested after 4 h. Transferrin, immunoglobulin M, and immunoglobulin A were the most resistant to the Tritrichomonas foetus extracellular proteinases, since 50% or more of the parent molecule remained after 24 h. The responsible proteinases were classified as cysteine (thiol) proteinases because cleavage was inhibited by the cysteine proteinase specific inhibitor, trans-epoxysuccinyl-L-leucylamido-(4 guanidino)butane and not by the serine proteinase specific inhibitor, phenylmethylsulfonyl fluoride. In addition, alpha 2-macroglobulin, but not alpha 1-antitrypsin, inhibits the action of the proteinases. The ratio of this naturally occurring inhibitor to the quantity of proteinases released may determine whether the above substrates are cleaved in vivo. Since these substrates are implicated in iron acquisition, cell adherence, and acquired immunity, Tritrichomonas foetus proteinases are likely to play a role in host parasite interactions. PMID- 1878817 TI - Characterization of interspecific hybrids within the Aspergillus nidulans group by isoenzyme analysis. AB - A comparison of interspecific hybrids within the Aspergillus nidulans species group was made by isoenzyme analysis. The gel electrophoretic patterns of the parental species were distinct for most of the enzymes tested. The hybrids were distinguishable from their parents by isoenzyme patterns. The appearance of novel bands in all the interspecific hybrids indicated that nuclear fusion could have occurred. In most hybrids the appearance of the parental bands showed nonpreferential, partial chromosome loss or repressive interaction between the genomes. The isoenzyme composition of the haploid segregants of the Aspergillus nidulans x Aspergillus rugulosus hybrid differed for some of the enzymes studied from that of the hybrid, suggesting that during segregation further interaction of the chromosomes took place. The results indicate a certain degree of genetic homology among the members of the Aspergillus nidulans species group. PMID- 1878818 TI - Role of cations in the flocculation of Saccharomyces cerevisiae and discrimination of the corresponding proteins. AB - Asexual yeast flocculation was studied using strong flocculents of Saccharomyces cerevisiae. The inhibitory effect of cations on flocculation is considered to be caused by competition between those cations and Ca2+ at the binding site of the Ca(2+)-requiring protein that is involved in flocculation. Inhibition of flocculation by various cations occurred in the following order: La3+, Sr2+, Ba2+, Mn2+, Al3+, and Na+. Cations such as Mg2+, Co2+, and K+ promoted flocculation. This promoting effect may be based on the reduction of electrostatic repulsive force between cells caused by binding of these cations anionic groups present on the cell surface. In flocculation induced by these cations, trace amounts of Ca2+ excreted on the cell surface may activate the corresponding protein. The ratio of Sr2+/Ca2+ below which cells flocculated varied among strains: for strains having the FLO5 gene, it was 400 to 500; for strains having the FLO1 gene, about 150; and for two alcohol yeast strains, 40 to 50. This suggests that there are several different types of cell surface proteins involved in flocculation in different yeast strains. PMID- 1878819 TI - Growing number of asthma cases, deaths baffles physicians. PMID- 1878820 TI - Helping patients travel by air. PMID- 1878821 TI - Nutrition and osteoporosis. PMID- 1878822 TI - Prenatal diagnosis: the medical genetics perspective. PMID- 1878823 TI - Recommended guidelines for uniform reporting of data on out-of-hospital cardiac arrests: the "Utstein style". PMID- 1878826 TI - Blood pressure during pregnancy in Canadian Inuit: community differences related to diet. AB - OBJECTIVE: To assess a possible relation between the incidence of hypertension during pregnancy and the consumption of fatty acids found in fish and sea mammals. DESIGN: Retrospective survey of pregnancy-induced hypertension; prospective diet survey. SETTING: Inuit women from seven communities in the Keewatin region of the Northwest Territories. PATIENTS: All women from Arviat (formerly Eskimo Point), Baker Lake, Chesterfield Inlet, Coral Harbour, Repulse Bay, Sanikiluaq and Whale Cove who gave birth between Sept. 1, 1984, and Aug. 31, 1987. MAIN OUTCOME MEASURES: All blood pressure measurements recorded during the pregnancy, incidence of pregnancy-induced hypertension in the seven communities, harvest of country food (food obtained from the land or sea rather than bought in a store) for six of the communities, self-reported consumption of fish, sea mammals and terrestrial mammals by a subgroup of the subjects and levels of phospholipid fatty acids in cord serum samples from a subgroup of the infants. MAIN RESULTS: Significantly lower mean diastolic blood pressure values during the last 6 hours of pregnancy were noted for the women from the three communities with a higher consumption of fish and sea mammals (78.2 [95% confidence limits (CL) 76.6 and 79.9] mm Hg) than for those from the four communities with a lower consumption of such food (81.5 [95% CL 80.1 and 82.9] mm Hg) (p less than 0.005). The relation between community diet type and blood pressure was independent of other factors. Correspondingly, the women from communities with a lower consumption of marine food were 2.6 times more likely to be hypertensive during the pregnancy than those from communities with a higher consumption of marine food (p less than 0.007). Parity (p less than 0.05) and prepregnancy weight (p less than 0.005) were also significantly associated with pregnancy-induced hypertension; however, the relation between hypertension and community diet type remained significant in logistic regression analysis (odds ratio 2.56, p = 0.03). The differences between the community groups were substantiated by the results of the diet survey, the levels of eicosapentaenoic acid (EPA) in the cord serum phospholipids and the harvest data. CONCLUSIONS: Increased consumption of fish may be beneficial for women at risk for hypertension during pregnancy. A prospective randomized trial of fish or EPA supplementation during pregnancy is warranted. PMID- 1878824 TI - Periodic health examination, 1991 update: 3. Secondary prevention of prostate cancer. Canadian Task Force on the Periodic Health Examination. PMID- 1878827 TI - Comparison of search strategies on CD Plus/MEDLINE. AB - OBJECTIVE: To compare two strategies for searching MEDLINE using the CD Plus/MEDLINE program on compact disc. DESIGN: Comparison study. INTERVENTIONS: Two search strategies were designed and executed for each of two topics (patient recruitment to clinical trials and attitudes of patients, the public and health care professionals toward clinical trials). Strategy A: searches based on key words selected from the medical subject heading (MeSH) tree structure. Strategy B: searches based on MeSH terms most frequently used to index a known set of relevant articles. Defined search restrictions were then applied. The effects of the restrictions on the absolute number of citations retrieved and on the proportion of relevant citations were assessed. OUTCOME MEASURES: Number of articles retrieved, number of relevant articles, precision and recall of each search strategy and overlap between strategies. MAIN RESULTS: Strategy A produced more citations than strategy B (recruitment 147 v. 38, attitude 366 v. 57) but had more inappropriate citations (recruitment 75 v. 17, attitude 265 v. 25). Both strategies produced 73 relevant recruitment citations and 101 relevant attitude citations. In the recruitment search although the precision did not differ significantly between strategies A and B the difference in recall was significant (98.6% v. 28.8% respectively, p less than 0.0001). In the attitude search strategy A had a lower precision than strategy B (27.6% v. 56.1%, p less than 0.0001) but a much higher recall (100% v. 31.7%, p less than 0.0001). CONCLUSIONS: Strategy A would be more valuable to researchers doing extensive reviews, whereas strategy B would be useful for the busy clinician who simply wants a few appropriate references quickly and is willing to sacrifice comprehensive retrieval in the interest of efficiency. PMID- 1878825 TI - Mechanisms and management of stroke in the elderly. AB - OBJECTIVE: To highlight the mechanisms, common causes and management of stroke in the elderly. DATA SOURCES: MEDLINE was searched for articles published from 1967 to 1990. The following key words were used: "stroke," "cerebrovascular disease," "elderly," "aging," "hypertension," "drug interactions," "etiology," "evaluation," "management" and "recovery of function." Original articles with large series of patients were reviewed in detail. STUDY SELECTION: Of about 750 original articles reviewed 116 were finally selected for detailed analysis. Those that dealt with cause, pathophysiologic features and management of stroke with emphasis on the elderly were chosen. DATA SYNTHESIS: With increasing age the incidence of stroke increases, cardiovascular reserve decreases, catecholamine responsiveness diminishes and cardiac arrhythmias become more common. Blood pressure, especially systolic, rises, and the benefits of its treatment become both more difficult to assess and less certain. In the elderly population embolic stroke, particularly that due to nonvalvular atrial fibrillation, is seen with increasing frequency. Because of postural hypotension, cardiac arrhythmias and overmedication, watershed infarction occurs more frequently with increasing age. Amyloid angiopathy now represents the most common cause of spontaneous intracerebral hemorrhage. CONCLUSIONS: Because of the altered drug metabolism and pharmacodynamics in the elderly the therapeutic armamentarium is growing, and so are the risks of such treatments. Stroke in the elderly poses unique problems that deserve distinctive solutions. Further research is needed to study the effect of cerebral ischemia to understand better how the older brain handles the stress of the ischemic insult. PMID- 1878828 TI - Statement on influenza vaccination for the 1991-92 season. PMID- 1878829 TI - Monounsaturated fatty acids and heart health. PMID- 1878830 TI - Influenza and vaccination. 1919. PMID- 1878831 TI - Treatment of influenza. 1919. PMID- 1878832 TI - Relations between Alberta midwives, MDs appear to be thawing despite high-profile trial. PMID- 1878833 TI - Case involving prominent BC psychiatrist puts medical profession on trial. PMID- 1878834 TI - Ethical issues concerning the HIV status of physicians and patients. PMID- 1878835 TI - Bill C-69: an obscure piece of legislation could spell doom for our health care system. PMID- 1878836 TI - When government demanded his charts, Newfoundland doctor demanded court date. PMID- 1878837 TI - Coping with schizophrenia: "when we are gone, what will become of our son?". PMID- 1878838 TI - Historic aspects of intravenous immunoglobulin therapy. AB - The earliest preparations of immunoglobulins (Ig) decreased the susceptibility of agammaglobulinemic patients to infections caused by pneumococci, Haemophilus influenzae, meningococci, streptococci, and Pseudomonas aeruginosa. Intramuscular administration of such preparations was painful and traumatic, especially for children. Ethanol-fractionated Ig could not be administered intravenously (IV) because the IgG molecules tended to aggregate and thus were more likely to produce anaphylactoid reactions. New Ig preparations, isolated at low pH (e.g., pH 4) in the presence of traces of pepsin to inhibit reaggregation, were well tolerated when administered IV. Thus a new era of treatment and prophylaxis of disease using IV Ig (IVIG) was launched. The IVIG preparations revolutionized the management of virtually all immunodeficiency syndromes characterized by failure of antibody responses. Amelioration of antibody deficiency secondary to certain chronic diseases or surgical trauma can be achieved with these preparations. Newer uses of IVIG include treatment of some autoimmune diseases; in some conditions, the beneficial influences may be attributable to antiidiotype antibodies present in the IVIG. Another likely explanation is that IVIG inhibits damage to cells and tissues by antibody-mediated cellular cytotoxicity or blocks phagocytosis that is facilitated by Fc receptor mechanisms. The value of IVIG in preventing infection in patients undergoing bone marrow or organ transplantation and in the treatment and prophylaxis of life-threatening infections in neonates and premature infants also is reviewed. PMID- 1878839 TI - Recent advances in intravenous immunoglobulin therapy. A symposium held in conjunction with the 15th International Cancer Congress. Hamburg, Germany, August 1990. PMID- 1878840 TI - Immune thrombocytopenic purpura and intravenous immunoglobulin. AB - The observation, in 1980, of a rapid increase in platelet counts as a result of administration of intravenous immunoglobulin (IVIG) in a patient with immune thrombocytopenic purpura (ITP) was followed by clinical studies confirming the efficacy of this new treatment alternative in ITP. Simultaneously, new sensitive assays using monoclonal antibodies against platelet glycoproteins showed that chronic ITP in adults and children is often an autoimmune disorder. There seem to be both immediate and long-term effects of IVIG in ITP which may be explained by mechanisms of action other than immunoglobulin G substitution. The mode of action of IVIG could correspond to interference with Fc receptors on phagocytes or be a result of antiidiotypic antibodies in IVIG that may induce secondary changes in the complex immunologic network. These immunomodulatory effects were the basis for the use of IVIG in the treatment of patients with other immune-related disorders. New aspects regarding definition and treatment of ITP, the possible mechanisms of action of IVIG, and the implications thereof are discussed and updated. PMID- 1878841 TI - Mechanisms of action of intravenous immunoglobulin therapy and potential use in autoimmune connective tissue diseases. AB - It has been almost 10 years since the observations on the efficacy of intravenous immunoglobulin (IVIG) in patients with autoimmune thrombocytopenic purpura. Over the next decade, IVIG was used in other types of autoimmune diseases. Much work has also been done on gaining a better understanding of the mechanism(s) by which IVIG exerts its effects in these autoimmune diseases. This review examines the proposed mechanisms of action of IVIG and establishes a rationale for the use of this type of therapy in systemic lupus erythematosus (SLE) and other autoimmune connective tissue disorders. Currently, only anecdotal reports are available on the treatment of SLE with IVIG. Nevertheless, studies thus far suggest that IVIG may be useful in selected SLE patients with cytopenias and cutaneous vasculitis and may have a steroid-sparing effect in patients with SLE and juvenile rheumatoid arthritis. In SLE patients with renal disease, it should be used cautiously because some patients have worsening of their renal function with IVIG infusions. These preliminary experiences suggest that multicenter controlled trials on the therapeutic use of IVIG in SLE and other connective tissue disorders would be important. PMID- 1878842 TI - Use of intravenous immunoglobulin in chronic lymphocytic leukemia. A brief review. AB - Chronic lymphocytic leukemia (CLL) is a disorder with multiple defects leading to an increased susceptibility to infection. Hypogammaglobulinemia is present in about 20% to 70% of patients with CLL. Intravenous immunoglobulin (IVIG) supplementation (400 mg/kg body weight every 3 weeks) prevented bacterial infections in these patients. An ongoing study is being conducted to compare doses of 250 mg/kg/mo with those of 500 mg/kg/mo in 36 patients included so far. As of this writing, the rate of infection in the two treatment groups was not significantly different, and no substantial loss of protection against bacterial infection was found in the lower-dose group. It seems likely that the lower dose is almost as effective as the standard therapy. If this is so, cost savings would be substantial. PMID- 1878843 TI - Use of intravenous immunoglobulin in acquired immune deficiency syndrome. AB - Patients infected with the human immunodeficiency virus (HIV) may have an antibody deficiency and a deficiency of cellular immunity. Intravenous immunoglobulin (IVIG) preparations may benefit HIV-infected children and adults with recurrent bacterial infections at doses of 200 to 400 mg/kg every 2 to 4 weeks. In addition, IVIG (1 to 2 g/kg) is effective at raising platelet counts to hemostatic levels in HIV-infected patients with idiopathic thrombocytopenic purpura and life-threatening bleeding. Indirect evidence also suggests that IVIG may be effective in preventing Pneumocystis carinii pneumonia. Finally, recent studies suggest that specific anti-HIV antibody preparations may have a therapeutic role, either as immunoglobulin concentrates or as immunoadhesions and immunotoxins. However, further investigations are needed to exclude antibody enhancement of HIV infection by the Fc receptor or the complement receptor. PMID- 1878844 TI - Use of intravenous immunoglobulin in various medical conditions. A Japanese experience. AB - The main clinical indications for intravenous immunoglobulin (IVIG) therapy in Japan are severe bacterial and viral infections as a result of primary and secondary immunodeficiencies, idiopathic thrombocytopenic purpura (ITP), autoimmune diseases, hematologic disorders, acquired immune deficiency syndrome, and Kawasaki disease. Experiences using IVIG to treat patients with severe infectious diseases, Kawasaki disease, and ITP are reported in this article. In patients with severe infections, IVIG showed some clinical benefits. In patients with Kawasaki disease, combined administration of IVIG and aspirin reduced the incidence of coronary artery lesions below that of aspirin alone or without therapy, and persistence of these lesions also decreased in patients who received combination therapy. Organ platelet sequestration, measured with indium 111 labeled platelets, showed a splenic pattern in good responders to IVIG, a hepatic pattern in fair responders, and a splenohepatic pattern in poor responders. These patterns might provide some insight into the use of IVIG. Some reaction mechanisms also are discussed. PMID- 1878846 TI - Preparing for war in the gulf. PMID- 1878845 TI - Recent advances in intravenous immunoglobulin therapy: Concluding remarks. Current trends and future directions. PMID- 1878847 TI - Nursing and war: transforming our legacy. PMID- 1878848 TI - No simple answer. PMID- 1878849 TI - A dilemma called Ellen. PMID- 1878850 TI - Street smarts. PMID- 1878851 TI - Canadian nurses and smoking. PMID- 1878852 TI - Success stories needed, now! PMID- 1878853 TI - Putting culture into curricula. PMID- 1878854 TI - Travel nursing. PMID- 1878855 TI - [Cohabitation]. AB - Even though it can be an attractive proposition for an elderly person, the idea of living with a family, or even their own family, should not be undertaken lightly. The author suggests three ways in which nurses can help; communication, sharing of responsibilities and coping with the burden. The main goal is to curb abuse of the elderly, a result of the enormous burden that falls on the shoulders of the caregiver. The solution to this situation is not easy. However, a simple tool in the form of a contract between the two parties, could be helpful. The author maintains that, regardless of pre-existing family relationships, it's best to look at this contract from a strictly objective point of view. All the factors that could come into play should be clearly stated by both parties. In this way, they will be better able to avoid misunderstandings and head off potential conflicts. PMID- 1878856 TI - [Transcultural validation of a measurement scale]. AB - This monography presents the validation study results of a new scale to measure family needs: The Family Needs Inventory (IBF) (Chartier and Coutu-Wakulczyk, 1988). The scale is available in both French and English from the Departement des sciences infirmieres of the Universite de Sherbrooke. Based on a perceptual framework, the IBF is a self-report scale composed of 33 items. It offers three different subscores of the importance of needs: the global score of needs, the intensity need index and the total number of needs. The IBF was validated on a sample of 400 subjects. These subjects were drawn from the adult population of immediate family members visiting a patient in surgical or medical intensive care units in three different geographical regions, in Quebec, northeast Ontario and France. The reliability yielded a 0.90 Cronback Alpha coefficient and the homogeneity coefficient for Spearman-Brown and Guttman procedures were 0.88 respectively. The principal component factor analysis and factorial matrices lead to examine the conceptual structure of five independent factors. PMID- 1878857 TI - [Altruism and the donor]. AB - On December 20, 1988, the government of France passed a law to protect people who voluntarily participate in biomedical research. This article makes extensive reference to a major study, titled From Biology to Ethics, by Jean Bernard, a well-respected authority in the field of bioethics. The author looks at models proposed by Bernard, as examples for health volunteers, in particular, the blood donor and the self-experimenter. To set the tone of the article, she recalls the concept of altruism, as first proposed by Auguste Comte, then makes a linkage between his philosophy and Bernard's point of view. By trial and error, in their discussions, various ethics committees and the French State Council have agreed upon what constitutes fair compensation under the law. Unlike their Canadian counterparts, medical researchers in France have free access to volunteers who are not in perfect health--e.g., the elderly, people suffering from kidney deficiency, cirrhosis of the liver, etc.--but these "experimental subjects" receive no monetary compensation. Thus, healthy and less-than-healthy volunteers do not receive equal treatment under the law. This inequity, added to the fear of what amounts to a tax on the human body and the difficulty of ensuring just compensation, is giving rise to a great deal of uncertainty. PMID- 1878858 TI - Rectal epithelial proliferation in persons post sporadic colorectal neoplasia. AB - Some studies have shown diffuse large bowel epithelial hyperproliferation in persons having colorectal neoplasia. Thus, measurements of rectal epithelial proliferation (REP) could be useful as a screening biomarker of risk for sporadic neoplasia. We examined REP, by autoradiography with tritiated thymidine, in 84 persons: 32 healthy volunteers, 37 who had had sporadic adenomas and 15 post cured sporadic colorectal cancer. Measurements of the labelling index (ratio of labelled to total number of crypt cells) showed a statistically insignificant but increasing gradient of hyperproliferation related to degree and invasiveness of neoplasia. However, this became significant when examining the proportion of labelled crypt compartments in each group and by comparing combined compartments 3 and 4 of cancer patients to non-cancer patients. Gender and age were found to be parameters that influenced the results. Using standard methods of analysis of REP, the lack of clear separation between risk groups limits the usefulness of REP measurements as a screening biomarker of risk for sporadic large bowel neoplasia. PMID- 1878859 TI - Identification of genes that exhibit increased expression after flat reversion of NIH/3T3 cells transformed by human activated Ha-ras oncogene. AB - By differential hybridization, we have isolated 14 cDNA clones corresponding to genes that are more highly expressed in the flat revertant cell line R1 than in the parental human Ha-ras oncogene-transformed NIH/3T3 cell line (EJ-NIH/3T3). From cross-hybridization experiments, we determined that 5 sequence families accounted for the 14 clones. DNA sequencing revealed that four out of five selected cDNA clones represented mitochondrial genes (cytochrome b, cytochrome c oxidase subunit II, NADH dehydrogenase subunits 1 and 4, respectively), whereas one cDNA clone was homologous to the alpha 2 (type I collagen gene. Although a Southern blot analysis of the studied cell lines showed similar copy numbers of mitochondrial genomes, the transcript levels of the mitochondrial genes were high in R1, intermediate in NIH/3T3 and low in EJ-NIH/3T3 and partially revertant R2 cell lines. alpha 2 (type I) collagen mRNA levels were high in R1 and NIH/3T3, intermediate in R2 and low in EJ-NIH/3T3 cells. These results suggest that a complex alteration of the expression of mitochondrial and extracellular matrix components may be closely associated with the flat reversion of the transformed cells. PMID- 1878860 TI - Effects of bombesin on the development of N-nitrosobis(2-oxopropyl)amine-induced pancreatic lesions in hamsters. AB - Bombesin (BBS) has been shown to promote pancreatic growth as well as the development of pancreatic (pre)neoplasia in rats. The present study was carried out to determine the effects of bombesin on pancreatic growth and on the development of pancreatic (pre)neoplastic lesions in hamsters treated with N nitrosobis(2-oxopropyl)amine (BOP). Bombesin caused an increase in growth of the pancreas accompanied by a decrease in the number of (pre)neoplastic ductular pancreatic lesions. Lorglumide (CR-1409) did not influence these effects of bombesin. It is concluded that in BOP-treated hamsters the effect of bombesin on the pancreas is not mediated by cholecystokinin (CCK). These data support the existence of species difference between rats and hamsters with regard to the effect of bombesin on pancreatic carcinogenesis. PMID- 1878861 TI - Modulation of 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone demethylation and denitrosation by rat liver microsomes. AB - The nicotine-derived N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone (NNK) is abundant in tobacco smoke and is a potent carcinogen in laboratory animals. We have characterized and compared methyl hydroxylation leading to formaldehyde formation (activation pathway) and denitrosation (putative deactivation pathway) of NNK using rat liver microsomes. Methyl hydroxylation was linear between 10 and 50 min and denitrosation was linear between 20 and 65 min. The ratio of nitrite/formaldehyde formation was smaller with 4 mM NNK (0.016) than with N-nitrosodimethylamine (NDMA) (0.037). Liver microsomes exhibited at least two apparent Km values (0.005 and 0.534 mM) for NNK methyl hydroxylation. In vitro methyl hydroxylation of NDMA and NNK were induced by pretreatment of the rat with isopropanol. Butylated hydroxytoluene pretreatment doubled the rate of microsomal denitrosation but did not affect the rate of methyl hydroxylation (+) Catechin is a flavonoid present in tea, wine and apple skin. We observed that 0.10 mM (+)-catechin inhibited methyl hydroxylation and denitrosation of 4 mM NNK by 40% and 62%, respectively. These results indicated that NNK could be deactivated by denitrosation. Hydroxylation of the NNK methyl group by rat liver microsomes was 34 times more extensive than denitrosation. PMID- 1878862 TI - Modifying role of Phyllanthus emblica and ascorbic acid against nickel clastogenicity in mice. AB - Nickel, a major environmental pollutant is known for its clastogenic and carcinogenic potential. Dietary inhibitors of mutagenesis and carcinogenesis are of particular importance since they may have a role in cancer prevention. In the present investigation, aqueous extract of edible dried fruits of Phyllanthus emblica, a well known medicinal plant, was fed to Mus musculus for seven consecutive days prior to treatment with different doses of nickel chloride (10, 20 and 40 mg/kg body wt.); the fruit extract significantly reduced the frequency of CA/cell, the percentage of aberrant cells and the frequency of micronuclei induced by all doses of nickel in the bone marrow cells of mice. Ascorbic acid, a major constituent of the fruit, fed for 7 consecutive days in equivalent concentration as that present in the fruit, however, could only alleviate the cytotoxic effects induced by low doses of nickel; at the higher doses it was ineffective. The greater efficacy of the fruit extract could be due to the interaction of its various natural components rather than to any single constituent. The study assumes importance in view of the widespread human exposure to nickel compounds. PMID- 1878863 TI - Suprasellar teratoma. PMID- 1878864 TI - In utero diagnosis of cerebro-oculomuscular syndrome. PMID- 1878865 TI - Learning disability and impairment of synaptogenesis in HTX-rats with arrested shunt-dependent hydrocephalus. AB - Using HTX-rats with congenital hereditary hydrocephalus, we used neuropathological methods, including quantitative Golgi study and neurobehavioral evaluation, to investigate the following problems. (1) What kind of damage does congenital hydrocephalus cause to developing brain tissue? (2) How much can the damage be repaired by ventriculoperitoneal shunting if performed at 4 weeks of age, enabling 4-week-old hydrocephalic rats to survive beyond sexual maturation? (3) What is the status of learning ability of long-term surviving rats with arrested shunt-dependent hydrocephalus? The findings of our study suggest that congenital hydrocephalus impairs the development and formation of the dendrites and spines of the cerebrocortical neurons. Following ventriculoperitoneal shunting, we confirmed that rats with arrested shunt-dependent hydrocephalus demonstrated learning disability in a light-darkness discrimination test using a Y-maze. The development of the dendrites and spines of the cerebrocortical neurons seemed to take place to some degree after shunting, but normal spine density could not be restored. Also suggested was a possible relationship between learning disability and a decrease in spine density, i.e., impairment of synaptogenesis. PMID- 1878866 TI - Spontaneously healed vein of Galen aneurysms. Clinical radiological features. AB - Vein of Galen aneurysms demonstrate a high tendency to thrombose, as extensive thrombophlebitis of the dural sinuses and deep venous system occurs frequently. This may be explained by the frequent detection of venous anomalies and retention of embryonic venous patterns such as the median prosencephalic vein. Twenty-one cases were reviewed (19 from the literature, 2 of our own cases): no typical syndrome for thrombosed aneurysm of the vein of Galen could be found; therefore, a preliminary diagnosis of clotted vein of Galen aneurysm was made in only half the cases. In all the remaining ones, pineal or III ventricle masses were suspected. Nevertheless, crescentic rimlike calcifications in the region of the vein of Galen can be found in 50% of cases. Only in half of the cases did angiography demonstrate the malformation filled by contrast medium, while in the remaining cases not only the aneurysm but also the deep Galenic venous system failed to opacify. Computed tomography and magnetic resonance scans demonstrated masses with high density/intensity values, with varying degrees of calcification. Knowledge of this pathological entity is important in order to avoid unnecessary surgical procedures. PMID- 1878867 TI - Cerebral cavernous malformations (cavernomas) in the pediatric age-group. AB - Cavernomas are vascular malformations composed of a compact mass of sinusoidal type vessels that are immediately contiguous with one another and have no intervening parenchyma. Cavernous malformations were previously held to be a rare pathology occurring predominantly in adults. New neuroradiological techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) demonstrate, on the contrary, that these lesions are also more frequent during childhood than was previously thought. In our institution we observed 17 cases of cavernous malformations in patients aged between 18 months and 16 years, 16 of whom were diagnosed after 1982. In 4 of these cases there was a documented familial history; in 2 multiple malformations were present. The most common site was the subcortical frontal region, but in 1 case the malformation was located in the pineal region. The most frequent (in 12 cases) initial symptom was hemorrhage, with the characteristics of an intracerebral hematoma. In 4 cases the initial symptom consisted of epileptic fits and 2 of these patients subsequently suffered hemorrhage. In one case the symptoms observed were those of an expansile process. All our patients underwent cerebral angiography and only in 1 case did this show a vascular abnormality. CT, performed in 16 patients, gave positive results in all cases. MRI, performed in 12 patients, gave highly significant images in all cases. Radical surgical removal of the malformation was performed in 15 of the 17 patients, and the results can be considered excellent in the majority of cases. Cavernous malformations are, therefore, more frequent lesions than had previously been thought, especially in pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878868 TI - Ocular complications of head injury in children. AB - Ocular complications occurred in 28% of children with head injury. Neuro ophthalmological lesions made up one-third of these complications, mostly involved the optic nerve, and were associated with other focal neurological signs more frequently than non-neural ocular complications. Lesions of the posterior visual pathways were rare but tended to be permanent. PMID- 1878869 TI - Intracranial tumors of the first year of life. A cooperative survey of the 1986 1987 Education Committee of the ISPN. AB - The introduction of new diagnostic tools for neuroimaging has resulted in the early recognition of congenital brain tumors. In the present report the authors describe an International Multicenter Series of 886 children with brain tumor, in whom the diagnosis was obtained during the first 12 months of life. Most of the tumors were located within the supratentorial compartment. In spite of a relatively high operative mortality, surgery still appears to be the more effective therapy. Radiotherapy in this age group is of little value due to the vulnerability of the infantile brain. At the present time, the use of chemotherapy is still controversial. PMID- 1878870 TI - Cerebral hydatid cysts in children. AB - Twelve children with intracranial cysts of Echinococcus granulosus underwent surgery during a period of 5 years and constituted 19% of all children operated on for intracranial space-occupying lesions. The more common symptoms were raised intracranial pressure (8 cases) and hemiparesis (7 cases). The total number of procedures was 14, with a standard craniotomy approach in 13. In 6 the cysts were removed without puncture or rupture, in 5 puncture and drainage were carried out before removal of capsule, and in 3 the cyst ruptured accidentally. Recurrence of multiple cysts occurred in 1 case and another patient was reoperated on twice for recurrent cysts after an operation in another center. There was no mortality. Non bacterial meningitis occurred in 2 cases. Although drainage of the cyst contents greatly facilitates removal, it also carries a risk of contamination; thus a traditional approach via a large craniotomy seems to be the safest choice. PMID- 1878871 TI - Posterior fossa cysts: clinical, neuroradiological and surgical features. AB - Various types of neuroimaging investigations were performed in 26 patients with posterior fossa cysts. The results were retrospectively analyzed to facilitate differential diagnosis and clarify indications for surgery. Four major findings were obtained in this study. First, posterior fossa intra-arachnoid cysts were encountered more frequently than expected and were found to be surgically treatable. Second, although IV ventricular cysts were categorized as Dandy-Walker malformation, Dandy-Walker variant, and persistent Blake's pouch in this study, the distinctions of neuroimaging findings between these three types are uncertain. Third, the diagnostic criteria for mega cisterna magna were established, and it was found to be a surgically untreatable condition. Finally, in cases with the following neuroimaging findings, surgery appears to be indicated: (1) occipital bossing or petrosal scalloping with distortion or obliteration of cerebrospinal fluid (CSF) cisterns of the posterior fossa; (2) compression and deformity of the brain surrounding the cyst; (3) radioisotope and/or computed tomography cisternographic findings suggestive of disturbance of intracystic CSF circulation; (4) a non-communicating cyst. PMID- 1878872 TI - Posterior fossa cysts: supratentorial shunt placement with ultrasound guidance. PMID- 1878873 TI - Burkitt's lymphoma: an unusual cause of childhood paraplegia. AB - In this paper we present two paraspinal Burkitt's lymphomas, with paraplegia. This entity is very rare in our country. In the evaluation of a paraplegic child, we believe that Burkitt's lymphoma should always be kept in mind. PMID- 1878875 TI - Nuclear Overhauser effects and the flexibility of saccharides: methyl beta xylobioside. AB - The behavior of methyl beta-xylobioside has been analysed by 1H-n.m.r. spectroscopy for solutions in water and methanol in the range - 15 degrees to 85 degrees. Experimental n.O.e. values did not change with temperature and solvent in contrast to the inter-glycosidic 3JC,H values. Experimental n.O.e. data accorded with the values calculated from time-averaged cross-relaxation terms. The tumbling times were determined from relaxation data and were in the sub-ns range. PMID- 1878874 TI - Primary intracranial extradural Burkitt-type lymphoma. A unique presentation with unilateral loss of vision in a child. AB - An unusual case of primary extranodal Burkitt's-type lymphoma of the frontal base dura and adjacent bone with intradural invasion is reported in a 5-year-old child who presented with unilateral loss of vision in the left eye. Tissue diagnosis was obtained through a craniotomy and the patient received radiotherapy plus intravenous and intrathecal chemotherapy. The tumor regression and improvement in vision was well documented by means of CT and visual evoked potential studies (VEP). A review of the literature on this exceptionally rare tumor is presented. PMID- 1878876 TI - Partial purification of esterases from rabbit serum and their use in regioselective deacylations of sugars. AB - 14C-Labelled methyl 2,6-di-O-pivaloyl-alpha-D-glucopyranoside was used as a substrate for the detection of esterase activity in the isolation of esterase II from rabbit serum. On treatment of methyl 2,6-di-O-pivaloyl-alpha-D glucopyranoside with rabbit serum and esterase II, the 6-O-pivaloyl group was removed selectively. Likewise, the 6-O-pivaloyl group was removed selectively from methyl 2-acetamido-2-deoxy-3,4,6-tri-O-pivaloyl-alpha-D-glucopyranoside. PMID- 1878877 TI - Synthesis and n.m.r. analysis of branched trisaccharide and pentasaccharide haptens of the beta-hemolytic streptococci group A and the preparation of synthetic antigens. AB - The synthesis of branched trisaccharide and pentasaccharide portions of the cell wall polysaccharide of the beta-hemolytic Streptococci Group A is described. The key dissaccharide acceptors, allyl or 8-(methoxycarbonyl)ocytol 3-O-(3,4,6-tri-O benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-4-O -benzyl - alpha-L rhamnopyranoside, in conjunction with a selectively blocked alpha-L rhamnopyranosyl chloride under Koenigs-Knorr conditions, afforded the branched trisaccharides in 81 and 62% yield, respectively. Analogously, glycosylation of the 8-(methoxycarbonyl)octyl disaccharide with a protected beta-D-GlcpNAc-(1--- 3)-alpha-L-Rhap-(1----3)-alpha-L-Rhap chloride gave the pentasaccharide in 43% yield. The key disaccharide acceptors were obtained, in turn, from the allyl or 8 (methoxycarbonyl)octyl rhamnoside acceptors and 3,4,6-tri-O-benzyl-2-deoxy-2 phthalimido-beta-D-glucopyranosyl chloride under Koenigs-Knorr conditions. The latter glycosyl donor has not been described previously. Removal of the protecting groups afforded the trisaccharide haptens as their 1-propyl and 8 (methoxycarbonyl)octyl glycosides and the pentasaccharide as its 8 (methoxycarbonyl)octyl glycoside. The compounds have been subjected to detailed analysis by two-dimensional n.m.r. methods. Preparation of the synthetic antigens followed coupling of the 8-(methoxycarbonyl)octyl glycosides to bovine serum albumin via the acyl azide intermediates. PMID- 1878878 TI - Deoxygenated and alkylated furanoses: Thorpe-Ingold effects on tautomeric equilibria and rates of anomerization. AB - 2-Deoxy-D-glycero-tetrose, 3-deoxy-DL-glycero-tetrose, 3-deoxy-3,3-di-C-methyl-DL glycero-tetrose, 3-C-methyl-DL-erythrose, 3-C-methyl-DL-threose, 2-deoxy-5-O methyl-D-erythro-pentose and 3-deoxy-5-O-methyl-D-erythro-pentose have been prepared, in some cases with 13C-substitution at the anomeric carbon, and characterized by 1H-(300 and 620 MHz) and 13C-n.m.r. (75 MHz) spectroscopy. The proportions of cyclic (alpha and beta furanoses) and acyclic (aldehyde and hydrate) forms were determined in aqueous (2H2O) solution, and ring-opening (kopen) and ring-closing (kclose) rate constants were measured by 1H and 13C saturation-transfer n.m.r. spectroscopy at p2H 5.0 (acetate buffer) and 60 degrees. The degree of furanose ring substitution was found to significantly affect both the thermodynamics and kinetics of furanose anomerization. Increased substitution enhances the proportion of cyclic forms in solution by stimulating furanose kclose. In contrast, furanose kopen was less affected by the degree of substitution; however, kinetic studies of 2-deoxyfuranose anomerization implicate furanose ring conformation as a potential determinant of kopen. PMID- 1878879 TI - Synthesis of 3'-deoxy-3'-fluorokanamycin A and 3',4'-dideoxy-3'-fluorokanamycin A. AB - 3'-Deoxy-3'-fluorokanamycin A (14) has been prepared by condensation of 6-azido 2,4-di-O-benzyl-3,6-dideoxy-3-fluoro-alpha-D-glucopyranlsyl++ + bromide (8) and 6 O-(2-O-acetyl-4,6-O-cyclohexylidene-3-deoxy- 3-tosylamino-alpha-D-glucopyranosyl) 2-deoxy-1,3-di-N-tosylstre ptamine (10). Compound 8 was obtained from 3-deoxy-3 fluoro-1,2:5,6-di-O-isopropylidene-D-glucofuranose in seven steps. 3',4'-Dideoxy 3'-fluorokanamycin A (22) has been prepared from 12 through selective 4' chlorodeoxygenation, a key reaction. Both 14 and 22 were more active than 3' deoxykanamycin A against both sensitive and resistant bacteria. PMID- 1878880 TI - Structural studies of the extracellular polysaccharide elaborated by Azotobacter vinelandii strain 1484. AB - The structure of the extracellular polysaccharide from Azotobacter vinelandii strain 1484 has been investigated, specific degradations and n.m.r. spectroscopy being the main methods used. It is concluded that the polysaccharide is composed of tetrasaccharide repeating-units having the following structure, [sequence: see text] in which Sug is 3-deoxy-D-threo-hexulosonic acid. The polysaccharide also contains a non-stoichiometric amount of O-acetyl groups, distributed over at least two positions. PMID- 1878881 TI - Structural features of the cell-wall polysaccharides of Asparagus officinalis seeds. AB - The fine structure of a beta-)1----4)-linked glucomannan from Asparagus officinalis has been determined by n.m.r. analysis of the oligosaccharides obtained by acidic and enzymic hydrolyses. Cleavage of the glucomannan with beta D-mannase from Aspergillus niger and purification by h.p.l.c. gave oligosaccharide fractions that contained Man (mannose), GlcMan (beta glucopyranosylmannose), Man2, Glc2Man, and Glc3Man as the major components. Simulated digestion of a polymer composed of randomly distributed monomers with the same Glc:Man ratio as glucomannan from A. officinalis led to the same polysaccharides. The random distribution of the monomers of glucomannan from A. officinalis was corroborated by the diffraction diagram of the raw flour, which indicated that the "in situ" glucomannan was amorphous, whereas both cellulose and mannans are crystalline. PMID- 1878882 TI - Chemical methods for the analysis of sulphated galactans from red algae. AB - Methods are reported that facilitate the structural characterization of complex sulphated galactans of the red algae. Two procedures have been developed for the production of alditol acetates from carrageenans and agaroids. Both procedures generate 3,6-anhydrogalactitol acetate from the easily destroyed 3,6 anhydrogalactosyl residues in near quantitative yield. The "double hydrolysis reduction" method involves preliminary hydrolysis under conditions sufficient to cleave all of the 3,6-anhydrogalactosidic bonds, but mild enough to avoid significant further degradation. The "reductive hydrolysis" method uses the acid stable 4-methylmorpholine-borane to reduce the 3,6-anhydrogalactose end groups as they are released during acid hydrolysis. An alditol acetate sample can be prepared from a polysaccharide in a single tube, ready for g.l.c. analysis, in less than 2.5 h, i.e. more quickly than by any previous procedure. Problems associated with incomplete methylation of sulphated carrageenans and agaroids by the Hakomori procedure have been overcome by first converting the sulphated polysaccharide into its triethylammonium salt form. The reductive hydrolysis method is effective for the production of partially methylated alditol acetates from the methylated polysaccharides, enabling the rapid determination of the substitution pattern of these polysaccharides. These improved analytical methods have been applied successfully to kappa-, iota-, and lambda-carrageenans, as well as some agars. PMID- 1878883 TI - Sulfation of some chemically-modified heparins. Formation of a 3-sulfate analog of heparin. AB - A modified form of heparin containing residues of nonsulfated alpha-L idopyranosyluronic acid (7) in place of the normal 2-sulfate (1) was sulfated with sulfur trioxide-trimethylamine in dimethylformamide at 0 and 25 degrees. Examination of the reaction products by n.m.r. spectroscopy showed that sulfation occurred selectively at C-3 of residue 7, to give a new polymer that may be described as a 3-sulfate analog of heparin. A slower substitution reaction led subsequently to sulfation at C-3 of 2-deoxy-2-sulfamino-alpha-D-glucopyranosyl 6 sulfate residues (2), although this was accompanied by partial N-desulfation of 2. An analogous pattern of O-sulfation-N-desulfation was observed for the residues of 2 in two other modified heparins, one containing residues of 2,3 anhydro-alpha-L-gulopyranosyluronic acid and the other residues of alpha-L galactopyranosyluronic acid, in place of residues of 1. The galacto diastereomer exhibited relatively low regioselectivity, as it was found to be sulfated at C-2 or C-2.3, or both. Selective resulfation of free amino groups gave the products that were examined for anticoagulant activity and susceptibility to enzymolysis by heparinase. Antithrombin-binding affinity measurements were also carried out. Although none of the materials had significant anti-Xa activity, nor were they affected by heparinase, their patterns of binding to antithrombinagarose were not dissimilar to that of heparin. PMID- 1878884 TI - A short synthesis of 1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-beta-D- glucopyranose and the corresponding alpha-glucosyl chloride from D-mannose. PMID- 1878885 TI - Structural analysis of a second acidic exopolysaccharide of Rhizobium meliloti that can function in alfalfa root nodule invasion. PMID- 1878886 TI - Vibrational Raman optical activity of carbohydrates. AB - Vibrational Raman optical activity (R.o.a.) spectra of a range of carbohydrates in aqueous solution, measured in back-scattering between 700 and 1500 cm-1, are presented. Features were revealed that appear to be characteristic of details of the stereochemistry. Effects associated with the glycosidic linkage in di- and oligo-saccharides are prominent. PMID- 1878887 TI - The structure of bergenin. AB - X-ray analysis of the 3,4,8,10,11-penta-acetate (3) of bergenin has confirmed the earlier structural assignments. PMID- 1878888 TI - Hydrogen bonding in the crystal structure of the tetrasaccharide stachyose hydrate: a 1:1 complex of two conformers. AB - The crystal structure of stachyose hydrate, O-alpha-D-galactopyranosyl-(1----6)-O alpha-D-galactopyrano- syl-(1----6)-alpha-D-glucopyranosyl beta-D fructofuranoside tetrahydrate, has been refined using X-ray data at 119 K. The crystal structure is a 1:1 complex of conformers which differ in the fructofuranosyl and glucopyranosyl residues. Each conformer has an associated hydrogen-bond structure which includes different sites for the water molecules. When superimposed in the crystal, this gives rise to two sites of 0.5 occupancy for one carbon and one oxygen atom of the fructofuranose component, and for three oxygen atoms of the glucopyranose component. The corresponding three carbon atoms of the glucopyranose component have anomalous thermal motion parameters. The four water molecules are distributed over nine sites, six with occupancy 0.5, two with occupancy 0.4, and one with occupancy 0.2. Four of the water sites are associated with one conformer, and four with the other. The hydrogen bonding includes infinite chains which are linked to form irregular ribbons, extending in the direction of the alpha axis. All hydroxyl, ring, and linkage oxygen atoms are involved in the hydrogen bonding, which includes two-centered, three-centered, and four-centered hydrogen bonds. PMID- 1878889 TI - Differences between the catabolism and tumour distribution of intact monoclonal antibody (791T/36) and its Fab/c fragment in mice with tumour xenografts revealed by the use of a residualizing radiolabel (dilactitol-125I-tyramine) and autoradiography. AB - Radioiodine-labelled 791T/36 monoclonal antibody (mAb) and its Fab/c fragment, consisting of one Fab arm and the Fc portion, have identical whole-body survival curves in BALB/c mice (t1/2 = 3.75 days). Therefore, these two forms of this antibody provide a suitable model for studying the role of valency in the targeting efficiency of antibodies to tumours in vivo. 791/T36 antibody and its Fab/c fragment were labelled either by direct iodination using the iodogen method (125I) or by dilactitol-125I-tyramine (125I-DLT), a residualizing label, which accumulates in the cells involved in degradation of the carrier protein. In tumour-bearing nude mice, the percentage of injected dose of mAb or Fab/c fragment reaching the specific 791T tumour was similar, and these proteins appeared to be catabolized at a similar rate in this tissue. mAb, but not the Fab/c fragment, was found to be very actively catabolized by the liver and spleen of tumour-bearing mice compared to control nude mice, this probably resulting from clearance of immune complexes. This effect was most pronounced when the mAb was labelled with 125I-DLT, the percentage of injected dose of mAb reaching the spleen and liver being higher than the percentage of injected dose reaching the tumour. This effect was not seen with the Fab/c fragment. Autoradiographic studies on tumour sections, which exhibit antigenic sites throughout the tumour mass, showed that the Fab/c fragment was already homogeneously distributed in the tumour 12 h after injection whereas the whole antibody was mainly localized at the periphery of the tumour. Those results suggest a "binding site barrier" effect. Overall, these results indicate that the highest valency and affinity may not be the optimal choice for mAb to be used for therapeutic purposes. PMID- 1878890 TI - Adriamycin(hydrazone)-antibody conjugates require internalization and intracellular acid hydrolysis for antitumor activity. AB - Adriamycin hydrazone (ADM-Hzn) immunoconjugates have previously been shown to exhibit antibody-directed antitumor activity in vitro and in vivo. In this report, the biological and biochemical properties of the mAb and linker were investigated. Conjugates prepared with two antibodies 5E9 [anti-(transferrin receptor)] and G28.1 (anti-CD37), (which internalize from the surface of target cells following binding) were more cytotoxic in vitro and had greater antitumor activity against Daudi B lymphoma tumor xenografts than a non-internalizing immunoconjugate prepared with mAb 2H7 (anti-CD20). In addition, the 13 acylhydrazone bond linking the drug to the mAb was labile at pH 5 and released unmodified ADM at a rapid rate (t1/2 = 2.5 h). Immunoconjugates prepared with an oxime linkage at the C-13 position were stable to acid and were not cytotoxic. These findings suggest that internalization of ADM-Hzn immunoconjugates and release of free ADM from the mAb in acidic intracellular compartments were important steps in the mechanism of action of ADM-Hzn immunoconjugates. PMID- 1878891 TI - In situ activation of mouse macrophages and therapy of spontaneous renal cell cancer metastasis by liposomes containing the lipopeptide CGP 31362. AB - We determined whether the intravenous administration of multilamellar vesicle liposomes (MLV) containing a lipopeptide analogue of a fragment from the cell wall of gram-negative bacteria (CGP 31362) can render BALB/c mouse alveolar macrophages tumoricidal in situ and reduce the incidence of spontaneous lung metastasis of syngeneic renal carcinoma (RENCA) cells. Alveolar macrophages (a) incubated in vitro with MLV containing CGP 31362 (MLV-31362) and (b) harvested from mice injected i.v. with MLV-31362 were rendered cytotoxic against the RENCA cells. Maximum cytotoxic activity of the macrophages was induced by injecting 5 mumol MLV consisting of 250 mg phospholipids and 0.5 mg CGP 31362. The single i.v. injection of 5 mumol MLV-31362 produced activation of macrophages that lasted for up to 4 days. Repeated i.v. injections of MLV-31362 produced a continuous antitumor activity in alveolar macrophages. To study the lipopeptide's effects on metastasis, we injected the left kidneys of BALB/c mice with RENCA cells. The kidney with growing tumor was resected 10 days later and, after a further 2 days, groups of mice were injected i.v. with MLV-31362 or with MLV-HBSS (twice weekly for 3 weeks). Treatment with MLV-31362 significantly decreased the median number of spontaneous lung metastases. These data demonstrate that the systemic administration of MLV-31362 can activate murine lung macrophages in situ and reduce the incidence of spontaneous RENCA lung metastases. PMID- 1878892 TI - Cytotoxic activity and phenotypic characteristics of lymphocyte subsets after therapy of cancer patients with interleukin-2. AB - After a 5-day period of continuous intravenous infusion of recombinant interleukin 2 (rIL-2) in seven patients with malignant melanoma or gastric or pancreatic cancer, different lymphocyte subsets were separated from patients' blood and tested ex vivo for cytotoxic activity against various tumour cell lines. Lytic activity was mediated by CD3+CD56+, CD3-CD56+, CD3-CD2+ and CD8+CD56+ lymphocytes. No cytotoxic activity could be observed within the CD3+CD56-, CD3+CD2+ or CD4+ T cell subsets. To characterize CD56+ cytotoxic cells further, the expression of other antigens on this population was analysed before and after IL-2 therapy. CD3, CD4, CD16 and CD57 antigens were weakly expressed, and the IL-2 receptor (CD25) was not detectable on these cells either before and after treatment with IL-2. In contrast, increased expression of CD2. CD8 and HLA DR antigens occurred following therapy. The divergence of CD3 and CD8 antigen expression after IL-2 therapy was caused by an increase in CD3-CD8+ cells, detectable as a low-density CD8+ subset. This study shows that cytotoxic activity of in vivo IL-2-activated killer cells is predominantly, but not exclusively, mediated by CD3-CD56+ lymphocytes, partially coexpressing the CD8 antigen and lacking the expression of CD16 antigens. PMID- 1878894 TI - Presence of activated lymphocytes in the urine of patients with superficial bladder cancer after intravesical immunotherapy with bacillus Calmette-Guerin. AB - To study the mode of action of intravesical bacillus Calmette-Guerin (BCG) immunotherapy in the prevention and cure of superficial bladder cancer, flow cytofluorometric analysis of the cellular immunological reaction in the urine of patients was performed. Fresh urine-derived leucocytes were obtained from eight patients before (t0) and 24 h (t24) and 48 h (t48) after repeated intravesical BCG instillations (at least 5 instillations). For two patients urine-derived leucocytes were investigated at the first BCG instillation. The number of leucocytes in the urine was markedly increased 24 h after repeated BCG instillations, indicating a local cellular immunological reaction induced by BCG. The mean number of cells per milliliter of urine at that time was 2.9 x 10(6) +/- 3.6 x 10(6) (n = 8). These leucocytes consisted mainly of granulocytes (75 +/- 11%, n = 8). In addition monocytes/macrophages (4 +/- 2%, n = 8) and T lymphocytes were present (1 +/- 1%, n = 5). The relative increase of monocytes/macrophages in the urine after BCG application tended to be higher compared to the other leucocyte subtypes. As T lymphocytes may play an important role in the BCG-mediated anti-tumour activity, subsets of lymphocytes were further characterized at t0, t24, and t48 after repeated BCG instillations. The lymphocyte population consisted mainly of T cells (86% CD3+, t0). Most of the T cells were CD4+ (helper/inducer) and were significantly decreased at 48 h (62 +/- 9% at t0 vs 49 +/- 6% at t48). Lymphocytes partly expressed HLA-DR antigens (44%, t0). The percentage of lymphocytes with interleukin-2 (IL-2) receptors (CD25+) was significantly increased at 24 h and 48 h, compared to pre-instillation values (19 +/- 11% and 10 +/- 4% vs 3 +/- 3% respectively). Natural killer cells (CD16+ and/or CD56+) and B cells (CD19+) were less numerous (10% and 19% at t0 respectively). After the first BCG instillation the increase in the number of leucocytes in urine seemed to be less compared to the numbers after repeated BCG instillations. Lymphocytes could not be detected in the urine collected before or after the first BCG instillation. In conclusion, we demonstrated the presence of considerable numbers of leucocytes in the urine 24 h after repeated BCG instillations, i.e. shortly after immunological activation. The antigen expression of the lymphocytes suggested that they may represent the lymphocytes in the bladder wall. Expression of HLA-DR and IL-2 receptors on lymphocytes indicated activation of T cells by the intravesical BCG treatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1878893 TI - Prospective assessment of the role of five tumour markers in breast cancer. AB - Retrospective analysis previously identified significant elevation of five tumour markers, carcinoembryonic antigen (CEA), ferritin, orosomucoid. C-reactive protein and erythrocyte sedimentation rate (ESR), in patients with systemic breast cancer and showed that changes in each of these markers individually correlated significantly with therapeutic response. In this study we have prospectively tested these findings. None of the five markers was significantly elevated in primary breast cancer compared to normal control or benign breast disease groups. They therefore appear to have no role either in screening or in the differential diagnosis of breast cancer. There was a significant elevation of all five markers in patients with systemic breast cancer (P less than 0.0001: analysis of variance) but sequential changes in CEA and ESR only correlated significantly with the UICC-assessed response. Prospective confirmation of the correlation between changes in serum CEA and ESR provides the basis for using these markers in the assessment of response to therapy in patients with systemic breast cancer. PMID- 1878895 TI - Lymphocyte activation in patients with acute myeloid leukaemia. Evidence for the presence of myeloblast antigen? AB - A group of 27 patients with acute myeloid leukaemia (AML), 15 with active disease and 12 in complete remission, were investigated for evidence of T cell activation. The parameters of T cell activation measured were the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble CD4 (sCD4) and soluble CD8 (sCD8) molecules and the proportions of T cells expressing the cytotoxicity linked cytoplasmic serine esterase. All patients studied with active disease had elevated sIL-2R and sCD8 molecules and an elevated proportion of T cells expressing serine esterase. Patients studied in complete remission also had elevated sIL-2R. sCD8 and serine-esterase-positive T cells, but values were lower than those studied in active disease. These patients were all studied in the absence of any ongoing or recent infection or exposure to homologous blood products, either of which could potentially affect these parameters. In the absence of any obvious alternative cause, we suggest these data indicate that AML leukaemia blast cells may be immunogenic and lead to the activation of cytotoxic T cells. PMID- 1878897 TI - Thrombolytic therapy: state of the art. PMID- 1878896 TI - Effect of advanced aging on ability of mice to cause regression of an immunogenic lymphoma in response to immunotherapy based on depletion of suppressor T cells. AB - This study shows that two therapeutic agents, anti-CD4 mAb and vinblastine, capable of causing T-cell-mediated regression of an established L5178Y lymphoma in 3-month-old mice, are incapable of causing regression of this tumor in 20- to 22-month-old mice. It is known that both agents are immunoaugmentative because of their ability to destroy tumor-induced CD4+ suppressor T cells preferentially. Therefore, the results indicate, that aged mice, unlike young mice, are not capable of generating therapeutic numbers of CD8+ effector T cells in the absence of suppressor cells. PMID- 1878898 TI - [Blood acceleration is the principal factor in coronary flow increase during exercise test]. AB - Continuous wave Doppler evaluation of the blood flow velocity in the internal mammary artery anastomosed to the left anterior descending coronary artery is a technique for assessing human coronary flow that shows a good reproducibility and lower change in Doppler angle between resting and supine exercise conditions. In this study the reciprocal changes which occur in coronary blood flow, coronary stroke volume, coronary resistance and blood pressure have been studied. During supine exercise coronary stroke volume remains constant and the increase of blood cells acceleration is necessary to have the shortening of cardiac cycle. This parameter is inversely dependent on the coronary resistances and directly dependent on blood pressure. As a consequence it plays the main role in increasing coronary blood flow during exercise. PMID- 1878899 TI - [Value of serial exercise tests after coronary angioplasty in relation to extension of heart disease and the degree of revascularization]. AB - With the aim of investigating the functional result of the coronary angioplasty (PTCA) and verifying the predictive value of the exercise test for detecting restenosis, 165 patients who underwent successful PTCA were evaluated through exercise stress tests performed 10, 75 and 165 days after PTCA and through coronary angiography performed 5 to 6 months after PTCA. The percentage of negative tests and the rate-pressure product (RPP) increased significantly with respect to the tests performed before PTCA, both in patients with single-vessel and those with multivessel disease. Maximal ST segment depression and ST/HR were significantly reduced only in patients with complete revascularization. The percentage of positive tests 10 days after PTCA was lower in patients with single vessel than in those with multivessel disease (2.5% versus 10.8%) and, of the latter, in patients with complete rather than incomplete revascularization (0% versus 13.5%). In patients with complete revascularization, the mean exercise time rose significantly (703 s versus 538 s). The percentage of positive tests increased progressively with time, in accordance with probable increasing restenosis. In comparison with the results of angiography, sensitivity of the exercise stress test proved to be poor (59%), especially in patients with single vessel disease (45%), while the specificity was very high (98%). The predictive value of a negative test was 77% in patients with multi-vessel and 87% in patients with single-vessel disease. The predictive value of a positive test was over 90% in both groups of patients. PMID- 1878900 TI - [Echocardiographic and cardioangiographic evaluation of non-Q infarction with isolated stenosis of the anterior descending artery]. AB - We studied with two-dimensional echocardiography and coronary angiography 2 groups of patients with one-vessel stenosis located on anterior descending (IVA) and previous acute myocardial infarction (AMI; means 19 days): 23 patients with spontaneous non-Q infarction (Group I), and 23 patients with Q infarction (Group II). Left ventricular function was better in Group I (echo score: 2.04 +/- 2.64, angiographic ejection fraction: 65.65 +/- 9.7 in Group I, echo score: 4.78 +/- 3.14, angiographic ejection fraction: 49.47 +/- 9.1 in Group II, p less than 0.001). Percent occlusion of IVA was lower in Group I and angiographic IVA caliper was significantly higher (p less than 0.05). Differences between groups were much more evident in subgroups with proximal stenosis of IVA: patients of non-Q subgroup had very good left ventricular function but frequently had post IMA unstable angina (78%). Our results underline usefulness of aggressive diagnostic and therapeutic approach in non-Q AMI, because of higher amount of myocardial a risk. PMID- 1878901 TI - [Syndrome of multiple cholesterol embolism after parenteral streptokinase therapy of acute myocardial infarct: description of an autopsy case]. AB - Syndrome caused by multiple cholesterol embolism can be seen as a complication in patients affected by acute myocardial infarction, treated with streptokinase thrombolytic therapy. Fragments of atheromatous plaques may embolize and occlude arterial vessels in different organs. Only the histological examination can give a reliable diagnosis, because symptomatology changes according to different localization of the emboli. An emblem case of this pathology observed by the Authors is described in this article. PMID- 1878902 TI - [Primary pulmonary hypertension: a review]. PMID- 1878903 TI - [Radiography of a congress and significance of a society]. PMID- 1878905 TI - Scanning electron microscopy of intrahepatic microvasculature casts following experimental hepatic artery embolization. AB - The initial site of occlusion of the intrahepatic microvasculature in rats following hepatic artery embolization was studied by scanning electron microscopy of microvasculature casts. The rats were divided into four groups: embolization with gelatin powder (n = 3), polyvinyl alcohol (n = 3, 125-150 microns), gelatin sponge (n = 3, 212-250 microns), and ionized oil. Not only the hepatic arteries but also vessels in the peribiliary plexus were occluded. However, the size of the hepatic arteries and vessels of the peribiliary plexus occluded correlated with the size of the embolic material, except in the case of the gelatin powder which occluded vessels smaller than the particle size. PMID- 1878904 TI - Percutaneous abscess and fluid drainage: a critical review. AB - Pertinent radiologic and surgical literature regarding abscess drainage was reviewed. Noted is the heterogeneity of disorders categorized as abscesses, and the variety of therapeutic approaches presently available. Specific abscesses are discussed based on body location and/or associated organ system. PMID- 1878906 TI - Ferromagnetism and magnetic resonance artifacts of platinum embolization microcoils. AB - We performed in vitro tests of ferromagnetism of platinum microcoils of two manufacturers. In addition, we performed in vitro magnetic resonance imaging (MRI) on these two devices to determine their levels of magnetic susceptibility artifact production. We found that both devices were nonferromagnetic and produced a very low level of artifact during MRI. In vivo MRI of a dog and 2 patients having previous placement of platinum microcoils was performed without coil migration or significant artifact production. Platinum microcoils are highly MR-compatible. PMID- 1878907 TI - Aneurysm formation in distal saphenous vein bypass grafts as a cause of graft failure. AB - Aneurysms of a reversed saphenous vein femoropopliteal bypass graft developed in two patients. In both patients, the aneurysm led to thrombosis and occlusion of the graft. One graft was reopened by intraarterial thrombolysis followed by local graft revision; the other required complete regrafting. This uncommon cause of graft occlusion should be considered before thrombolysis. PMID- 1878908 TI - Percutaneous reconstruction of the aortic bifurcation with Palmaz stents: case report. PMID- 1878909 TI - Embolization of an intraparotid false aneurysm of the external carotid artery: case report. AB - A case of posttraumatic false aneurysm of the terminal part of the main external carotid artery involving the entire parotid gland is presented. Embolization with two microcoils allowed immediate thrombosis of the false aneurysm. The lumen of the external carotid artery remained open. Facial paralysis resolved. The atypical clinical presentation and the therapeutic steps in such a case are described. PMID- 1878910 TI - Embolic control of lumbar artery hemorrhage complicating percutaneous renal biopsy with a 3-F coaxial catheter system: case report. AB - A case is presented in which massive retroperitoneal hemorrhage from the left first lumbar artery complicating a percutaneous renal biopsy was successfully controlled by superselective embolization with microcoils. An anterior radiculomedullary artery (artery of Adamkiewicz) originated from the lumbar artery. To minimize the risk of ischemic damage to the spinal cord from embolization, the extravasating branch of the lumbar artery had to be superselectively catheterized using a 3-F coaxial catheter system. Computed tomography (CT) scan localized the hematoma within the left posterior pararenal space in the retroperitoneal space. PMID- 1878911 TI - Cystic artery pseudoaneurysm: a rare cause of hemobilia. AB - Gallstone-induced cystic artery pseudoaneurysm is a rarely encountered cause of hemobilia. A few reports have appeared in the radiologic literature. We report such a case as a reminder of its uncommon occurrence. PMID- 1878912 TI - Intermittent hydronephrosis as a cause of a false-negative pressure-flow study. AB - A case is reported of a negative pressure-flow study in a patient with intermittent hydronephrosis. This is the first known report of a properly performed pressure-flow study failing to diagnose obstruction due to the intermittent nature of the obstruction itself. This case also supports the concept that the ureteropelvic junction (UPJ) can be intrinsically normal in patients with intermittent hydronephrosis secondary to a crossing renal vessel. It also reaffirms the need to study these patients while they are symptomatic. PMID- 1878913 TI - Angiodysplasia associated with Meckel's diverticulum: case report. PMID- 1878914 TI - A device for CT-guided needle punctures: technical note. AB - A device is presented to increase placement accuracy and to reduce localization scans during CT-guided biopsies. The device provides an accurate anticipation of the needle path by external radiopaque landmarks. PMID- 1878915 TI - Effects of fluoride, lithium, and strontium on growth and acid production of mutants streptococci and Actinomyces viscosus. AB - Eight strains of mutants streptococci and two strains of Actinomyces viscosus were studied to determine (1) their relative sensitivities to fluoride, lithium, and strontium and (2) whether lithium or strontium interact to enhance the known antimicrobial effects of fluoride. Analyses of variance of the data revealed a major inhibition of growth and acid production by fluoride, but not by lithium or strontium. Fluoride (5 mg/l) inhibited cell growth of all strains tested by a mean of 17% and total titratable acid production by a mean of 31%. However, there were marked differences between the strains. Mean total titratable acid was inhibited by fluoride least with the A. viscosus strains (15%) and most with the mutans streptococci (34%). Although interactions among the elements were statistically significant, they were generally slight in magnitude. PMID- 1878916 TI - Interactions of sanguinarine and zinc on oral streptococci and Actinomyces species. AB - Sanguinaria extract, which contains benzophenanthridine alkaloids, has been used as a folk medicine for many years. Minimum inhibitory and minimum bactericidal concentrations (MIC and MBC values) for sanguinarine were determined for common and etiologically important plaque bacteria. Because the efficacy of sanguinarine is believed to be enhanced by zinc, isobolograms were assessed to determine their mode(s) of interaction. Hydrogen ion concentration influenced the inhibitory activity of both sanguinarine and zinc. For sanguinarine, at the optimum pH (6.5), MIC values were 4 or 8 micrograms/ml for Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguis, Actinomyces viscosus and Actinomyces naeslundii. MIC values were 0.125-0.50 mmol Zn/ml. MBC values ranged from 1 to 8 mmol Zn/ml at pH 5.5. Isobologram data revealed that sanguinarine and zinc interacted synergistically. Viadent oral rinse, which contained 300 micrograms sanguinaria extract/ml and 0.2% zinc chloride (14.9 mmol Zn/l), was inhibitory to all strains tested. MIC values were 1 or 2% (ml Viadent oral rinse/100 ml aqueous solution) for all strains except A. viscosus for which the MIC value was 12% (vol/vol). PMID- 1878917 TI - A computer program designed for the analysis of data from rat caries studies. AB - The Keyes method for scoring dental caries in the rat animal model has been used as the basis for a computer-assisted scoring system on the Apple Macintosh personal computer that is described here. The program provides the ability to draw on diagrams of the rat molar dentition and to enter enamel lesion scores (L, E) and dentinal lesion scores (Ds, Dm, and Dx) for all aspects of the molars. The scores and drawings may be changed at any time. Total carious teeth and totals of L, E, Ds, Dm, and Dx are automatically calculated and presented upon user command. Error trapping for typographical errors is provided. In addition, the program provides automatic storage of the collected information, searching and sorting on any of the experimental parameters and on-disk help files that can be accessed from any place within the program. The capacity to obtain printed copy of any or all of the stored information is provided in the program. The program also enables the creation of external data files containing totals for carious teeth, in addition to L, E, Ds, Dm, and Dx totals for each animal of each group represented in the data base. These files are suitable for the transfer of data to commercially available programs for graphical and statistical analyses. The programming technique we describe could be extended to other model systems with standardized scoring for oral disease. PMID- 1878918 TI - Extracellular administration of lactate dehydrogenase and its effects on human plaque pH and acid anion concentrations. AB - The effect of lactate dehydrogenase (LDH) on human plaque pH and acid anion concentrations in vivo was investigated. Rinsing with sucrose solutions supplemented with LDH (1 or 2 U/ml) gave rise to reduced pH fall, decreased cH area and an increase in the mean minimum pH when compared with rinsing with sucrose only (p less than 0.05). Mean acid anion estimations showed that plaque fluid concentrations of lactate, acetate and proprionate significantly decrease (p less than 0.05) following rinsing with sucrose containing LDH at both levels and decreases in succinate when 1 U/ml LDH was present, whereas formate concentrations were only significantly lower when 2 U/ml LDH was added to sucrose rinses. It is thought that the ability of LDH to produce an alteration in the acid end-products of plaque metabolism may provide some protection against dental caries. PMID- 1878919 TI - Oral sugar clearance in children compared with adults. AB - The aim of the present investigation was to study oral sugar clearance of various types of foodstuffs in children of different ages in comparison with adults. Thirty children and 20 adults were selected constituting five groups, each containing 10 individuals: 3-, 7-, 15-years-olds and adults, all with normal salivary secretion rate, and adults with low salivary secretion rate (dry mouth patients). Oral sugar clearance was studied using three glucose-containing products: solution, tablet and biscuit. Repeated saliva samples were collected every other minute, between 1 and 11 min after the intake, with a convenient method suitable for very young children. For that purpose, a small circular paper disc, absorbing approximately 20 microliters of saliva, was placed under the tongue for 10 s. The glucose concentration of the samples was then analyzed enzymatically. The results showed that, in children, the oral sugar clearance became faster with increasing age. The adults and the 15-year-olds had similar patterns of clearance, while the dry mouth patients had the slowest oral clearance of all groups. The 3- and 7-year-olds showed the greatest variation in oral clearance between the various foodstuffs; the solution had faster clearance than both the biscuit and the tablet. The main conclusion from this study is that young children (3- and 7-year-olds) have both slower salivary sugar clearance and larger variation in clearance among various foodstuffs than older children and adults. PMID- 1878920 TI - Effect of different fluoride levels in dentifrice on the development of approximal caries. AB - The development of approximal carious lesions was monitored on annual bite-wing radiographs obtained from 315 children, participating in a controlled dentifrice trial; 157 of these children had used a dentifrice containing 250 ppm F and 158 a dentifrice containing 1,000 ppm F (both as NaF) during a 3-year period as the sole fluoride supplement. The total number of surfaces recorded was 6,099 at the baseline and 7,358 at the final examination. In the 250-ppm F group 393 approximal lesions (297 in the outer half, 96 in the inner half of the enamel) and in the 1,000-ppm F group 399 lesions (319 and 80, respectively) were diagnosed at the baseline examination. After 3 years the fraction of sound surfaces had decreased from 79% at baseline in both groups to 54% in the low-F group and to 58% in the high-F group. Concurrently, the relative number of enamel lesions had increased from 13% in both groups to 26% in the low-F group and 24% in the high-F group. 66% of the surfaces in the low-F group and 60% in the high-F group remained sound, and the relative proportion of static enamel lesions was 26 and 28%, respectively. The differences did not reach statistical significance. The results imply that higher fluoride levels in the dentifrice are more effective in retarding the initiation of caries, while they do not differ with respect to the progression of radiographically detectable approximal carious lesions. PMID- 1878921 TI - Ornithine decarboxylase immunoreactivity in the pituitary gland. A comparative lightmicroscopical study. AB - In the present study efforts are made to localize ornithine decarboxylase enzyme protein--the key enzyme of polyamine biosynthesis--in the adenohypophysis of different vertebrates by means of immunocytochemistry. The antigenic expression of ornithine decarboxylase was revealed in the pituitary of the clawed frog (Xenopus laevis D.), but not in rat and human adenohypophysis. The immunocytochemical results are compared with the staining pattern of the periodic acid-Schiff-reaction. No correlation between these results and the immunocytochemically obtained data has been found. Conclusions are drawn from the location of the enzyme and possible phylogenetic and humoral regulation mechanism. PMID- 1878922 TI - Comparative study of the lethal effects of near-UV light (360 nm) and 8 methoxypsoralen plus near-UV on plasmid DNA. AB - We have studied the lethality produced on pBR322 by near-UV radiation and by 8 Methoxypsoralen plus near-UV (PUV treatment). Samples of pBR322 DNA were irradiated with increasing fluences of 360 nm-light either in the absence or presence of 400 molecules of 8-Methoxypsoralen (8-MOP) per plasmid molecule. We have estimated to what extent the global lethality of PUVA treatment is due to the presence of psoralen adducts in DNA or to radiation itself. In order to analyse the involvement of DNA repair mechanisms in the removal of plasmid lesions, several strains of E. coli (differing in their repair capacities) were used as recipients of the treated plasmids. Results showed that excision and recombination participate in the repair of near-UV-induced plasmid lesions. Repair of PUV-induced lesions showed an even greater requirement of the excision pathway. Besides, a slight increase on plasmid mutation frequencies was observed after near-UV or PUV treatment in wild type and uvrA cells. Estimation of the contribution of 8-MOP to the global lethality of PUV treatment showed that only the excision pathway was involved in removing psoralen adducts from plasmid DNA, suggesting the involvement of the recombinational pathway in the repair of near UV-derived lesions. PMID- 1878923 TI - Presence of meprobamate-like molecules in rat neuromuscular junction. Immunohistochemical demonstration at light- and electron-microscopic levels. AB - The localization of meprobamate-like (MPB-like) molecules in the neuromuscular junction of rats has been investigated at light- and electron- microscopic levels with the peroxidase-antiperoxidase (PAP) immunohistochemical method, using a purified antiserum obtained from rabbits immunized with a meprobamate-bovine serum albumin (MPB-BSA) conjugate. The immunoreaction was found surrounding synaptic vesicles and in protuberant deposits situated in the post-synaptic membrane. These facts suggest the existence of endogenous MPB-like molecules in neuromuscular junction and that the immunostained protuberant deposits should mark the receptors of those molecules. PMID- 1878924 TI - X-ray microanalysis of cerium in mouse spleen cells demonstrating acid phosphatase activity using high voltage electron microscope. AB - An X-ray microanalytical study was carried out on mouse spleen cells demonstrating acid phosphatase (AcP-A) activity, using cerium (Ce) as the capture agent at different accelerating voltages. The enzyme reaction products were localized in the lysosomes and appeared dense and homogeneous. The presence of cerium was confirmed by X-ray microanalysis. The main spectral line of cerium was present at La = 4.84 keV. The result showed that the X-ray count of Ce and the background (B) decreased significantly with increasing accelerating voltage between 100 and 400 kV. The change was more pronounced between 100 and 200 kV and thereafter, minimal change was noted. Consequently, the computed P/B ratio increased appreciably with increasing accelerating voltage. Thus, significant P/B ratio in X-ray microanalysis of biological specimens could be achieved by using a medium voltage transmission analytical electron microscope at accelerating voltage between 300 and 400 kV. PMID- 1878925 TI - Ultrastructural analysis of asialoglycoprotein receptor mediated endocytosis in cultured newborn hepatocytes. AB - We examined the receptor-mediated endocytosis of asialoglycoproteins in thick sections of cultured hepatocytes of newborn rats by high voltage electron microscope. The organelles involved in endocytosis are revealed ultrastructurally using colloidal gold particles coupled to lactosylated bovine serum albumin. Keeping the cells at 4 degrees C the marker binds to the cell surface showing microvilli, and is not internalized. Increasing the temperature to 37 degrees C, we observed that within 5-15 min. the marker enters the intracellular endocytic organelles close to the cell surface. After 60 min. the marker is found in the larger and deeper endocytic organelles and in large lisosome-like vesicles. We find that the process of endocytosis in newborn cultured hepatocytes is similar to that found in cultured cells of adult rats, but the process of internalization is slower. PMID- 1878926 TI - Immunohistochemical localization of S-100 protein subunits (alpha and beta) in dorsal root ganglia of the rat. AB - The distribution of S-100 protein and their subunits (alpha and beta) in lumbar dorsal root ganglia of adult rat was investigated immunohistochemically using monoclonal antibodies against the S-100 protein, alpha-subunit and beta-subunit of S-100 protein. The conventional S-100 protein antibody stained both neurons (large and intermediate in size; 20.3% and 41 +/- 3.2 microns of diameter) and glial cells (satellite cells and Schwann cells). The immunoreaction for the alpha subunit was observed in the perikarya of some large and intermediate sized neurons (17.2%, 45.6 +/- 6.1 microns of diameter), satellite cells and Schwann cells, whereas the beta-subunit immunoreactivity was found principally in glial cells, and in a scarce number of large and intermediate sized neurons (2.8%, 43.3 +/- 5 microns of diameter) Our results demonstrate that a subpopulation of large and intermediate sized neurons of lumbar DRG contain alpha- and beta-subunits of S-100 protein, being alpha-subunit predominant. Furthermore, the satellite glial and Schwann cells contain also the two subunits but mainly beta-subunit. These data confirm previous studies about the presence of S-100 protein in neurons of the central and peripheral nervous system. PMID- 1878927 TI - Discrepancy between biochemical normalization and morphological recovery of jejunal mucosa during postischemic reperfusion in presence of the xanthine oxidase inhibitor oxypurinol. AB - An increased formation of oxygen free radicals in the reperfused rat small intestine is concluded from accumulations of oxidized glutathione, of thiobarbituric acid-reactive substances and of 4-hydroxynonenal. Xanthine oxidase inhibition prevented these biochemical changes. The histological and electronmicroscopic studies of intestinal sucosa showed significant structural deteriorations already at the end of the ischemic period obviously due to disturbances of cellular energy metabolism. The extent of dosage was increased during the reperfusion without qualitative changes of the pattern of structural dosage. The beneficial effects of oxypurinol on biochemical criteria which occurred already in the early phase of reperfusion were not reflected in significant morphological differences within the first hour of reperfusion. Differences of morphological findings between oxypurinol-treated and untreated animals could be observed after longer periods of reperfusion--during the regeneration of the tissue. PMID- 1878928 TI - Experimental changes in the amount of maternally stored ribosomes affect the translation efficiency of ribosomal protein mRNA in Xenopus embryo. AB - The amount of maternal free ribosomes in developing Xenopus embryos has been experimentally modified; an increase was obtained by microinjection of purified ribosomes into fertilized eggs, and a decrease was induced by treatment with a drug which reduces the amount of free ribosomes. The effect of this manipulation on the partition of the ribosomal protein mRNA (rp-mRNA) was analyzed during embryo development; it was observed that when ribosomes available for translation are in excess, polysome loading with rp-mRNA decreases. Conversely, when ribosomes are scarce, polysome loading of rp-mRNA increases. These experiments, which artificially stress events observed in the course of development, indicate that there is a relationship between the availability of ribosomes in the cells and the utilization of rp-mRNA for synthesis of ribosomal proteins, as already suggested by previous observations on r-protein synthesis during embryogenesis. PMID- 1878929 TI - Changing ultrastructure of thyrotrophs in the rat anterior pituitary after thyroidectomy as studied by immuno-electron microscopy and enzyme cytochemistry. AB - The characteristic ultrastructure of thyrotrophs of the rat anterior pituitary was observed by immuno-electron microscopy and enzyme cytochemistry with increasing time after thyroidectomy (TX). The rough endoplasmic reticulum (ER) became dilated, the intracisternal granules reacted to serum raised against thyroid stimulating hormone (TSH) around 21 days after TX, and lysosomes and peculiar structures with positive acid phosphatase activity were present. The administration of thyroxine (T4) to the thyroidectomized rats resulted in the reformation of secretory granules, a reduction of dilated cisternae of rough ER and the activation of the lysosomal systems. Morphological features indicating that the TX-cells might be derived from growth hormone (GH) cells or cells other than TSH cells, previously suggested by some researchers, were not recognized in the present study. The amount of serum and pituitary TSH was measured by radioimmunoassay (RIA), and correlated well with the morphological changes. These results indicate that the TX-cells are hypertrophied hyperfunctioning TSH cells that have been affected by the lack of negative feedback of thyroid hormone. PMID- 1878930 TI - Localization of hydroxyindole O-methyltransferase-synthesizing cells in bovine epithalamus: immunocytochemistry and in-situ hybridization. AB - Hydroxyindole O-methyltransferase (HIOMT)-immunoreactive cells and melatonin synthesis were demonstrated in bovine epithalamus (including the pineal gland) with monoclonal antibodies and cRNA probes to HIOMT. The HIOMT-immunoreactive product was present in the cytoplasm of pinealocytes. All identifiable pinealocytes were clearly labeled in the pineal gland. The expression of the HIOMT gene was first identified in pinealocyte cytoplasm by in-situ hybridization (ISH). The distribution of the hybridization-positive cells in the pineal gland was compatible with that revealed by immunocytochemistry using the monoclonal antibody to HIOMT. In addition, HIOMT transcripts were found in the medial habenular nucleus, and the habenular and posterior commissure; they may correspond to S-antigen-immunoreactive cells demonstrated in the same regions of the hamster and the mouse. In these regions, the hybridization-positive cells did not exhibit HIOMT-immunoreactivity; thus, cells devoid of immunoreactivity may synthesize but rapidly transport the newly synthesized proteins. These results indicate (1) that the conversion of N-acetylserotonin into melatonin takes place in the cytoplasm of pinealocytes, (2) that some epithalamic cells in the habenular area may synthesize melatonin, and (3) that melatonin may act as a chemical messenger in centrally directed processes, as shown by using S-antigen immunocytochemistry. PMID- 1878932 TI - Pentosome--a new connective tissue component--is a subunit of amyloid P. AB - A new minute connective tissue structure, referred to as "pentosome", has been investigated by electron microscopy and its nature has been examined by immunoperoxidase tests. Pentosomes are 3.5-nm wide, particulate structures that have been observed in the posterior chamber of the eye, the connective tissue spaces of the mouse foot-pad and the matrix of the mouse EHS tumor. They are usually found in the vicinity of microfibrils whether they are free or associated with elastic fibers. They tend to be organized into groups forming a three dimensional semi-crystalline lattice at 10-nm intervals, but are connected by fine filaments. At high magnification, pentosomes appear as hollow structures composed of two parallel pentagons, which respectively measure 2.7 and 3.5 nm, and are held together by a cross-bar. A series of immunoperoxidase tests has only shown antigenicity against a serum protein, the amyloid P component. However, pentosomes are only about one-third the size of the 8.5-nm wide, disk-like segments of the amyloid P molecule. Since they could be subunits of these molecules, such subunits were prepared and compared with pentosomes; they appeared to be identical. It is concluded that the pentosomes found in connective tissue are AP subunits. PMID- 1878931 TI - Chicken cardiac myofibrillogenesis studied with antibodies specific for titin and the muscle and nonmuscle isoforms of actin and tropomyosin. AB - Myofibrillogenesis was studied in cultured chick cardiomyocytes using indirect immunofluorescence microscopy and antibodies against alpha- and gamma-actin, muscle and nonmuscle tropomyosin, muscle myosin, and titin. Initially, cardiomyocytes, devoid of myofibrils, developed variable numbers of stress fiber like structures with uniform staining for anti-muscle and nonmuscle actin and tropomyosin, and diffuse, weak staining with anti-titin. Anti-myosin labeled bundles of filaments that exhibited variable degrees of association with the stress fiber-like structures. Myofibrillogenesis occurred with a progressive, and generally simultaneous, longitudinal reorganization of stress fiber-like structures to form primitive sarcomeric units. Titin appeared to attain its mature pattern before the other major contractile proteins. Changes in the staining patterns of actin, tropomyosin, and myosin as myofibrils matured were interpreted as due to longitudinal filament alignment occurring before ordering in the axial direction. Non-muscle actin and tropomyosin were found with sarcomeric periodicity in the initial stages of sarcomere myofibrillogenesis, although their staining patterns were not identical. The localization of the "sarcomeric" proteins alpha-actin and muscle tropomyosin in stress fiber-like structures and the incorporation of non-muscle proteins in the initial stages of sarcomere organization bring into question the meaning of "sarcomeric" proteins in regard to myofibrillogenesis. PMID- 1878933 TI - Cytoskeletal filaments in embryonic chick myocardial cells as revealed by the quick-freeze deep-etch method combined with immunocytochemistry. AB - The three-dimensional organization of cytoskeletal filaments associated with the myofibrils and sarcolemma of the myocardial cells of early chick embryos was studied by the rapid-freeze deep-etch method combined with immunocytochemistry. In the endoplasmic region of saponin-treated myocardial cells, 12-14 nm filaments formed a loose network surrounding nascent myofibrils. These 12-14 nm filaments attached to the myofibrils and some of them converged into Z disc regions. In the non-junctional cytocortical region thinner 8-11 nm filaments composed a dense network just beneath the sarcolemma. In myofibril terminating regions at the sarcolemma, i.e., the fascia adherens, 3-5 nm cross-bridges were observed among the thin filaments. In Triton-permeabilized and myosin subfragment 1 (S1)- treated samples, subsarcolemmal 8-11 nm filaments proved to be S1-decorated actin filaments under which there was a loose network of S1-undecorated filaments. Subsarcolemmal S1-decorated actin filaments had mixed polarity and attached to the sarcolemma at one end. A loose network of S1-undecorated filaments among myofibrils in the endoplasmic region was revealed to consist of desmin-containing intermediate filaments after immuno-gold staining for desmin. These networks connecting myofibrils with sarcolemma were assumed to play an important role in integrating and transmitting the contractile force of individual myofibrils within early embryonic myocardial cells. PMID- 1878935 TI - Maturation-related changes in mass and elemental contents of secretory granules as measured by electron-microprobe. AB - The relationship between granule density, protein content, and Ca and S contents were studied in two secretory granule fractions, from parotid glands of the rat, previously shown to constitute different stages in granule maturation. The density of the lighter fraction was between 1.133 and 1.142 g/ml, while that of the heavier fraction was greater than 1.142 g/ml. The mean protein content of the denser granules was 12% greater than that of the lighter granules (P less than 0.03), while the dry-mass elemental concentrations in the two granule fractions were unchanged. These results indicate that protein is added to granules during the maturation process (presumably by vesicular traffic), and that the resulting increase in granule density is not driven simply by decrease in water content and/or increased concentrations of inorganic Ca or S in the granules. The elemental concentration values also indicate that the diffusible elements permeate the granule membrane during the fractionation procedures. PMID- 1878934 TI - Patterns of mineralization in vitro. AB - Various patterns of mineralization are found in the organism during fetal and postnatal development. Different findings and theories have been published in the literature with regard to the mechanisms of mineralization, many of which are controversely discussed. In the present study the different patterns of mineralization observed in the organoid culture system of fetal rat calvarial cells were investigated by electron microscopy. In organoid culture, calvarial cells grow and differentiate at high density, and deposition of osteoid and mineralization of the matrix occur to a very high extent. Different types of mineralization could be observed more or less simultaneously. It was found that hydroxyapatite crystals were formed at collagen fibrils as well as in the interfibrillar space. Mineralization was frequently seen in necrotic cells and cellular remnants as well as in extra- and intracellular vesicles. Addition of bone or dentin matrices or the artificial hydroxyapatite Interpore 200 to the cells caused an increased mineralization in the vicinity and on the surface of the matrices with and without participation of collagen. On previously formed mineralized nodules, an apposition of mineralizing material appeared due to matrix secretion by osteoblasts. It is concluded that initiation of mineralization occurs--at least in vitro--at every nucleation point under appropriate conditions. These mineralization foci enlarge by further apposition as well as by cellular secretion of a mineralizing matrix. Furthermore, cell necroses may liberate mineralizable vesicles. All these patterns of mineralization are the result of different activities of one cell type. PMID- 1878936 TI - Immunoreactive Tamm-Horsfall protein in the kidney and skin of the frog Rana temporaria. AB - Tamm-Horsfall protein (THP) is the main protein in normal human urine, and is found in the thick limb of the Loop of Henle in human kidney, and in other mammalian species. The skin of the frog. Rana temporaria, has similar physiological properties to this mammalian kidney tissue. In the present study, an immunohistological method involving an antibody to human THP was used to investigate the distribution of this distinctive protein in frog kidney and skin, and to compare its distribution with that found in the kidney tubules of rat and rabbit. THP-positive material was detected in the distal renal tubules and nephric duct of frogs, and was also located in the superficial epidermis of skin. It is suggested that its presence in amphibian skin is consistent with the hypothesis that THP is an important component of tissues that absorb sodium and chloride ions, but remain impermeable to water. PMID- 1878937 TI - Dissociation of photoreceptor cells from the pineal organ of the lamprey, Lampetra japonica. AB - Photoreceptor cells, nerve cells and supporting cells were dissociated from the pineal organ of the river lamprey, Lampetra japonica, by the use of 10 U/ml papain solution at 28 degrees C for 20 min, followed by repeated trituration. With the aid of Nomarski interference-contrast optics, photoreceptor cells, nerve cells and supporting cells were readily identified. Electron-microscopic examination revealed that isolated photoreceptor cells display an outer segment endowed with a few lamellar disks and connected to the inner segment (ellipsoid) via a connecting cilium. The structural features of the dissociated photoreceptor and supporting cells strongly resemble the morphology of the respective cellular elements in situ. We succeeded in culturing dissociated cells for time periods up to 48 h when the procedure described in detail was applied. PMID- 1878938 TI - Calcium content and concretions of pineal glands of young and old rats. A scanning and X-ray microanalytical study. AB - Calcium content and pineal concretions were studied in young (2-3 months) and old (28 months) Wistar rats. Samples, deep-frozen by liquid propane isopentane and freeze-dried were analysed by means of X-ray microanalysis in a scanning electron microscope. Total semi-quantitative measurements revealed that pineals of old rats showed a marked increase of calcium compared with the pineals of young rats. It is thus suggested that a calcium-rich environment is responsible for the growth of pineal concretions, which only appear in old rats. Pineal calcifications in rats could thus be an indicator of aging and/or of a degenerating state. PMID- 1878939 TI - The fine structure of lamellate cells in the brain of amphioxus (Branchiostoma lanceolatum, Cephalochordata). AB - The lamellate cells of amphioxus have round nuclei, and cytoplasm with many mitochondria and a large amount of glycogen. Each of these cells projects a highly modified, branched cilium into the central canal, where it characteristically forms lamellar structures. Primary branches and secondary lamellae often contain accessory microtubules that are not derived from the axonema. The functional and evolutionary significance of this cell type is discussed in relation to the ciliary photoreceptors found in other chordates. PMID- 1878940 TI - Calretinin and calbindin in the retina of the developing chick. AB - Calretinin and calbindin-D28k are two calcium-binding proteins that are present in largely different sets of nerve cells in the central nervous system. Their appearance during development of the chick retina was studied by immunohistochemistry and Western blots. The patterns are mature one day before hatching. Each cell type acquires its characteristic calcium-binding protein several days after its differentiation has started, but in most cases before morphological maturation is complete. There is also an early phase of calbindin immunoreactivity in many immature amacrine cells, and of calretinin immunoreactivity in the presumptive photoreceptor layer, suggesting that these proteins may have distinct functions in differentiating cells. PMID- 1878941 TI - Clusters of nerve cell bodies enclosed within a common connective tissue envelope in the spinal ganglia of the lizard and rat. AB - A careful search for groups of nerve cell bodies enclosed within a common connective envelope was made in the spinal ganglia of the lizard and rat using a serial-section technique. Nerve cell bodies sharing a common connective envelope were found to be more common in the lizard (9.4%) than in the rat (5.6%). These nerve cell bodies were arranged in pairs, or, less frequently, in groups of three. At times, they appeared to be in immediate contact, with no intervening satellite cells; at others, they remained separated from one another by a satellite cell sheet. The clusters of nerve cell bodies enclosed within a common connective envelope probably result from the arrest of developmental processes in the spinal ganglion. It is possible that, as a result of the cell arrangement here described, certain neurons electrically influence other sensory neurons at the level of the ganglion. PMID- 1878942 TI - Ultrastructural study of a cytoplasmic bridge connecting a pair of erythroblasts in mice. AB - A unique cytoplasmic connection between erythroblasts was studied by electron microscopy in mouse hemopoietic tissues (fetal liver, fetal and neonatal spleen and adult bone marrow). Many pairs of interphase erythroblasts were connected by a "cytoplasmic bridge" that was very thin and sometimes long in comparison with telophase bridges. The stage of maturation of the cells in a pair was similar. Small numbers of microtubules ran along the cytoplasmic bridge; a mid-body was not seen. The plasma membrane at approximately the middle of the bridge bulged to form a ring-shaped ridge filled with dense amorphous substances; this was called a "bulging ring." Thus, the cytoplasmic bridge between erythroblasts did not morphologically correspond to the telophase bridge in the usual cytokinesis. Cytoplasmic bridges were observed in various differentiating stages of erythroblasts, whereas other cell types of the hemopoietic lineage did not have such a bridge. The cytoplasmic bridge is unique to erythroblasts and provides an evidence for the atypical cytokinesis of the erythroblastic lineage. PMID- 1878944 TI - Islets of preadipocytes highly committed to differentiation in cultures of adherent rat adipocytes. Light- and electron-microscopic observations. AB - Cultures of adherent mature adipocytes, obtained from collagenase-digests of adipose tissue of the rat, invariably contain rapidly proliferating, fibroblast like cells despite the washing and centrifugation procedures employed during isolation of the fat cells. Such spindle-like cells originate from low-density structures, which we term "islets", that are present, together with the mature adipocytes, in the floating layer of the digest of adipose tissue. Islets are found in preparations from adult (3-4 months old) as well as aging (17-24 months old) rats. By light- and electron microscopy, the islets appear as clusters of closely associated cells containing a variable amount of lipid-like material. Cells of endothelial or pericytic origin are also present in the islets. Within a few hours of culture, the islets give rise to those spindle-like cells that have been seen to proliferate in the cultures. By 36-48 hours, such cells begin to accumulate lipid droplets and, by 150 hours, assume the morphology of small mature adipocytes (diameter 20-35 microns) with a large central lipid droplet. The pattern of differentiation of these cells recalls that of preadipocytes derived from the stromal-vascular fraction of adipose tissue digests. Nonetheless, the extent and rapidity of their adipose conversion, as well as the culture conditions necessary for differentiation, are different and suggest that these cells are a substantially uniform subpopulation of adipocyte-precursor cells highly committed to differentiation. PMID- 1878943 TI - Immunoreactivities for chromogranin A and B, and secretogranin II in the guinea pig entero-endocrine system: cellular distributions and intercellular heterogeneities. AB - The family of the chromogranin/secretogranin proteins consists of three major subtypes: chromogranin A (CgA), chromogranin B (CgB) and secretogranin II (SgII). These proteins are present in various endocrine cells and organs. Using immunohistochemistry on serial semithin sections, we have investigated ten endocrine cell types of the guinea pig gastro-intestinal tract for their content of chromogranin/secretogranin proteins. The gastrin cell was the only cell type containing immunoreactivities for all three chromogranin subtypes. The majority of entero-endocrine cells showed immunoreactivities for CgA and SgII. Somatostatin cells lacked immunoreactivities for any of the chromogranins. Moreover, the densities of the corresponding immunoreactivities varied among the different endocrine cell types or even among endocrine cells of a given population. Aminergic endocrine cells (e.g., enterochromaffin and enterochromaffin-like cells) regularly exhibited strong immunoreactivities for CgA but failed to react for SgII. In peptidergic endocrine cells, the immunoreactivities for both CgA and SgII ranged from dense to faint. This was also true for CgB in gastrin cells. Hence, only CgA and SgII can be considered as regular constituents of entero-endocrine cells. The intercellular differences in immunoreactivities for all three chromogranin subtypes indicate that every endocrine cell has its own composition of chromogranin/secretogranin proteins. This may be due to differences in the regulation of biosynthesis or processing of the chromogranins in individual endocrine cells; this in turn might be related to the functional states of endocrine cells. PMID- 1878945 TI - Autoradiographic evidence that transport of newly synthesized neuropeptides is directed to release sites in the X-organ--sinus gland of Cardisoma carnifex. AB - Sections of isolated X-organ--sinus gland neurosecretory systems of the crab, Cardisoma carnifex, were studied by light- and electron microscopy with conventional and autoradiographic procedures. The somata only were exposed to a pulse of 3H-leucine (5 min-5 h) and the entire system perfused with chase medium for various times (1-72 h) before fixation. Within 1 h, radiolabel is concentrated in Golgi complexes and nascent granules of both large and small somata. Label is undetectable in the terminal region following a 10 h chase. It is found in the nerve tract near terminals at 14 h, while after a 19 h chase, label is concentrated in terminal profiles abutting blood sinuses of the neurohemal organ (sinus gland). Following a 72 h chase, label is distributed throughout the terminal region. Each of the six morphologically distinguishable terminal types shows labelling. These observations show that the vast majority of newly formed granules are initially transported to release sites of the perisinus terminals. They thus provide an explanation for previous analyses indicating that newly synthesized peptides are preferentially secreted. PMID- 1878946 TI - The three-dimensional cytoarchitecture of the interstitial tissue in the rat kidney. AB - The cytoarchitecture of the interstitial tissue of the rat kidney was studied by combined scanning and transmission electron microscopy. The renal interstitium is composed of an elaborate network of stellate sustentacular cells. In the cortex, sustentacular cells radiate thin branching processes to form a fine reticulum, which supports intertubular spaces. In the medulla, these cells extend thick processes horizontally along the basal surfaces of the thin limbs or vasa recta, reinforcing their attenuate walls. The horizontal processes connect with each other at their terminals, compartmentalizing the interstitial space into thin layers. The medullary sustentacular cells contain abundant small lipid droplets. The network of sustentacular cells houses vasa recta, keeping them in parallel position to each other and to the tubules. The arterial vasa recta are accompanied by pericytes, which frequently contain lipid droplets larger in size than those in the sustentacular cells. Venous vasa recta extend numerous basal microvilli, which anchor the venous wall to adjacent tubules or vessels. Numerous free cells, round in shape, are found in the sustentacular cell network, especially in the cortex. They consist of macrophages and occasional lymphocytes. Some macrophages extend long pseudopodia, while others make intimate contact with lymphocytes, suggesting their high level of activity. PMID- 1878947 TI - Lipopolysaccharide and opioids activate distinct populations of Mytilus edulis immunocytes. AB - Studies in Mytilus edulis have indicated that immunoregulatory activities comparable to those in vertebrates also exist in invertebrates. Mytilus immunocytes resemble cells of the vertebrate monocyte/macrophage lineage and are activated by similar substances. We searched for differential effects of opioids on these cells in comparison with those of lipopolysaccharide (LPS), in order to determine if different subpopulations of immunoactive hemocytes are involved. We showed that Mytilus immunocytes respond to LPS in a fashion similar to that in vertebrate granulocytes by flattening, and increasing in cellular perimeter and mobility, that LPS administered in vivo results in a lowering of the number of free hemocytes that can be obtained from the animal, and that distinct immunoactive cell populations seem to exist since apparently different subsets of cells react when exposed to LPS or opioids and the opioid antagonist naloxone. PMID- 1878948 TI - Ontogenetic changes in the regenerative ability of chick retinal ganglion cells as revealed by organ explants. AB - Whereas mature neurons in the central nervous system (CNS) of birds lack the capability of regenerating axons after injury, embryonic nerve cells are able to do so. The time course of this decline of regenerative ability was investigated in ganglion cells from embryonic chick retinae. Retinal strips from 7- to 19-day old embryos (E7-E19) were explanted and cultured in vitro. The numbers of retinal ganglion cell (RGC) neurites that had extended during the first 22-23 h incubation, their elongation rates, and morphometric parameters of the growth cones were measured to characterize the regenerative behavior. We observed two periods of decline in neuritic growth: the first from E7 to E9, and another from E14 to E19. The first decrease may reflect a gradually disappearing portion of neurons which produced their axons de novo. The second decline coincides with the major period of synaptogenesis by ganglion cell axons in ovo. The time required for initiation of axonal outgrowth increased, accordingly, from less than 3 h in explants from younger retinae (E7-E16) to 10-12 h for E17 and E19 explants. Axonal elongation rates ranged between 36 micron/h and 56 micron/h (mean values) for E7-E13 explants, but were significantly lower for cells from E14-E19 retinae (13-21 microns/h). Morphologically, neurites and growth cones for RGC explanted before E17 were characterized by their high variability. They possessed more filopodia than mature neurons (E17, E19), fasciculated to a higher degree and branched more frequently. In addition, older neurites appeared "stiffer" and were morphologically simpler.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1878950 TI - Ultrastructural visualization of exocytosis in the pig pineal gland. AB - The pinealocytes of the pig contain conspicuous dense bodies, the nature and role of which are not yet fully elucidated. The aim of this study was to demonstrate whether or not these structures are involved in the secretion process. The tannic acid-Ringer incubation (TARI)-method, which allows a clear-cut ultrastructural study of secretory discharge by exocytosis, has been used. The results indicate that pig pinealocytes release the content of the dense bodies with an amorphous inner structure into the extracellular space via exocytosis and that this secretion is quantitatively important. The secreted material is proteinaceous in nature; this indicates that polypeptides are released by the pineal. PMID- 1878949 TI - Effect of cytokines on thymic hematopoietic precursors. Phenotypic and electron microscopic study. AB - We have previously shown that the interaction of thymocytes with thymic accessory cells (macrophages and/or interdigitating cells) is one of the factors required for thymocyte activation. Precursors of both thymic accessory cells and thymocytes are included in the CD4- CD8- Mac-1- Ia- subpopulation, and their respective maturation and/or activation may be modulated by granulocyte macrophage colony-stimulating factor, interleukin 1 and interleukin 2. When CD4- CD8- thymic cells are activated with granulocyte-macrophage colony-stimulating factor plus interleukin 2, both macrophages and interdigitating-like cells are present, as shown by electron microscopy. When activated with interleukin 1 plus interleukin 2, the interdigitating-like cell is the only accessory cell present. In both culture conditions, large clusters are formed between interdigitating cells and lymphoid cells. These results have led us to propose two-step signals for thymocyte proliferation: first, the maturation of macrophages under granulocyte-macrophage colony-stimulating factor control and the production of interleukin 1, and secondly, the maturation of interdigitating cells under interleukin 1 control, their clustering with thymocytes which are then activated. PMID- 1878951 TI - Three-dimensional model of tight junction fibrils based on freeze-fracture images. AB - To study the three-dimensional structure of tight junction fibrils, the epithelia of the jejunum and epididymis of adult mice were examined by the freeze-fracture technique in unfixed and in aldehyde-fixed specimens. The fibrils have a stronger affinity for the protoplasmic (P) face of the lipid bilayer in fixed material, and for the external (E) face in unfixed and rapidly frozen material. Therefore we can observe the fibrils both from the outside and inside of the cell. Fibrils appearing on the P-face are smoothly contoured ridges and rows of hemispherical particles, while those appearing on the E-face are exclusively rows of hemispherical particles. Based on these observations, we wish to propose a new fibril model for the tight junction. There are two distinctive types of junctional elements. One type is composed of a smooth and continuous strand in the external view of the cell, but is studded with hemispherical bulgings in its internal view. This type will be referred to as the "continuous type". The other type is bead-like, and will be referred to as the "particle type". The relative proportion of these two types of elements appearing within a tight junction network differs among tissues. PMID- 1878952 TI - Distribution of anionic sites in gut tissue: an electron-microscopical study. AB - A new one-step incubation method using cationic gold colloid was applied to reveal anionic moieties in rat colonic mucosa. Gold particles were detected in all cellular nuclei, basement membranes, mast cell granules and collagen fibres, while the luminal surfaces of all vascular endothelial cells were devoid of gold label. Application of the method for detection of anionic domains under various conditions is discussed. PMID- 1878953 TI - [The discover of Lyme disease in Fujian Province]. AB - By means of indirect fluorescent antibody assay (IFA), Borrelia burgdorferi B31 strain was used for antigen, to detect the 2579 serum specimens from forest area in 9 counties of Fujian province, 47 cases in 8 counties were detected positive, positive rate was 1.82%. By epidemiological investigation, we found that peoples who infected with Lyme disease, 91.67% of them (22/24) have been bited by Ixodes, and 6 cases suffer typical clinical symptoms of Lyme disease, 9 cases have the similar or somewhat typical symptoms. We found Lyme disease could be cross reaction to leptospirosis, in this paper the serum specimens which Lyme disease and leptospirosis all positive, we were not consider them to Lyme disease for time being, no matter the patients may be have suffer double infection. The indentification of the cross-reaction between Lyme disease and leptospirosis should be further studied. PMID- 1878954 TI - [A preliminary study on the behavior of 225 drug abusers and the risk factors of HIV infection in Ruili county Yunnan Province]. AB - We carried out the investigation on 225 drug abusers in L village, Ruili county in March 1990, and tested blood specimens of intravenous users (IVDUs) for HIV infection. Of 225 drug abusers, 153 (68.0%) were by inhaling and 72 (32.0%) were by intravenous. In the recent two years, the proportion of IVDUs in drug abusers sharply increased from 13.5% in 1988 to 30.5% in 1989, and 32.0% in spring 1990. Blood specimen were collected from 64 out of 72 IVDUs, among them 51 (79.7%) were HIV-positive. The findings of relation between HIV infection and drug abuse suggested that the sharing common syringes with others and failure of their sterilization were independent risk factors. PMID- 1878955 TI - [A case-control study of stomach cancer in Changle, Fujian Province--by the risk state analysis]. AB - In order to detect the risk factors of stomach cancer in Changle county, a case control study was undertaken. The present paper reports on the results of risk state analysis. It showed that taking mildewed and heavily salty food, having bad eating habits, family history of tumour, less consumption of fresh vegetables, meat and bean products were the risk factors of stomach cancer in this county. PMID- 1878956 TI - [Ten-year longitudinal observation on malaria epidemiology in Shandong Province]. AB - This paper reports the results of 10-year longitudinal observation on malaria epidemiology at 11 malaria surveillance stations in areas with different epidemiological types in Shandong province, by the blood examination of patients with fever, the observation of mosquito density and the malaria IFAT etc. It was shown that the method, through analysing the epidemic trend of malaria, could evaluate fairly the reliability of the comprehensive measures with particular emphasis on controlling the source of infection in malaria control. PMID- 1878957 TI - [Distribution of serotypes and biotypes of Campylobacter jejuni/coli strains from ten provinces/cities in China]. AB - The Lior's schemes were used for serotyping and biotyping 301 C. jejuni/coli strains isolated from different hosts in ten provinces/cities of China. No difference was found between the serotype distributions of the strains isolated from various areas. Forty-one serotypes were detected. Of the isolates, 86.71% were typable and 3 new serotypes, LIO N-1, N-2 and N-3, were developed. The differences were proved among the serotype distributions of the isolates from different areas. It was shown that one host could be infected by two (or more) strains belonging to different serotypes at the same time. No association between a particular biotype and serotype was observed. PMID- 1878958 TI - [Endogenous posterior uveitis and toxoplasma infection: a case-control study]. AB - The present study was first carried out to evaluate the effects of toxoplasma infections on endogenous posterior uveitis in Tian in city. In this report, 118 cases of endogenous posterior uveitis and 236 clinical and health controls were studied by 1:2 pair match case-control method. The clinical controls were OPD patients without uveitis and the health controls were normal persons. The prevalence rate of toxoplasma infection in three groups were 31.4%, 11.9% and 9.3% respectively. The differences of three groups was higher significant. The odds ratio (OR) of toxoplasma infection in posterior uveitis was 3.72 (2.17 6.39). The difference of the two controlled groups was not significant. The odds ratio of toxoplasma infection in central exudative retinochoroiditis and panuveitis were 4.78 and 3.33. The toxoplasma infection was not significantly related to the optic retinitis. The results suggest that toxoplasma infection as a suspect agent of endogenous posterior uveitis. PMID- 1878959 TI - [Transplacental transmission of hepatitis B virus]. AB - Thirteen fetuses from terminated pregnancies were collected. The age of gestation ranged from 20 to 32 weeks. Nine mothers of these fetuses were positive for HBsAg, 5 of them were also positive for HBeAg, HBV DNA. Four mothers were negative for HBsAg. DNA was extracted from fetal leukocytes, liver, heart, spleen, kidney, etc. HBV DNA was detected by dot hybridization. The results showed that HBV DNA was positive in leukocytes and liver of a fetus whose mother was positive for HBsAg, HBeAg. The liver HBV DNA of the fetus was about 23.1 kb by Southern blot. When digested by Hind II, it was about 3.2 kb 13.4 kb and 23.1 kb. So our data might serve as an evidence of transplacental transmission of HBV infection. Transplacental transmission seemed to be related to serum HBsAg, HBeAg, HBV DNA and leukocyte HBV DNA of mother. PMID- 1878960 TI - [The specificity of plague antigen FI in PHA]. AB - It were inoculate a total of the 15 type and 13 group Leptospira strains to the Rattus flavipetus and Rattus lose 137 rates in Lei Zhou peninsula. As the antisera acquired, it has been examined the lyso-agglutinative test in Leptospira strains. Up to standard serum it was to test for PHA of plaque, employing the sensitized blood cell by FI from 4 antiplague institutes. All of tests are negative. In addition to test for 3 immune sera, Hemorrhagic Fever antisera (Immunized animals Apodemus agraius, Rattus norvegicus, Mouse and Rabbit), anthrax antiserum, there were be negative by PHA of plague test, at same time by RIA test also be negative. Therefore all of the other antisera would not be interfering with specificity of the plague FI antiserum in PHA or RIA test. PMID- 1878961 TI - [Study of prevention technique of fluorosis caused by burning coal containing fluoride-reducing fluoride content of indoor air with the help of sesled range]. AB - Effects of reducing fluoride content of indoor air by the Mushan improve coal range, and the heated bed designed and made by these authors are quantitatively evaluated in this paper. The result shows that only heated bed can be effective to prevent fluorosis caused by burning coal containing fluoride. PMID- 1878962 TI - [Detection of C-reactive protein in patients with epidemic cerebrospinal meningitis by solid phase radioimmunoassay]. AB - A modified solid phase RIA was developed for the quantification of C-reactive protein in human serum and CSF. The lowest measurable amount detected by this method was 5 ng/ml (0.25 ng/well). The serum levels in 68 healthy blood donors were with in the range from 0.028-3.4 micrograms/ml, with a median value of 0.166 micrograms/ml (mean = 1.57 micrograms/ml); whilst those in 63 patients with epidemic cerebrospinal meningitis were up to 520 micrograms/ml with a median value of 77.5 micrograms/ml (mean = 88.46 micrograms/ml). This is 400-500-fold higher than that of the normal. The levels of CRP in the sera collected during acute stage of the infection (ranged from 28.5-540 micrograms/ml, with a median value of 200 micrograms/ml, mean = 200.6 micrograms/ml) were 400-fold higher than that after recovery (ranged from 0.1-54 micrograms/ml, with a median value of 0.53 micrograms/ml). In addition, lower levels (0.07-150 micrograms/ml, median = 2.07 micrograms/ml) of CRP were detected in CSF. These results markedly revealed that the CRP reflected the characteristics of an acute phase protein in the infection, and would be usefull for the differential diagnosis of bacterial and nonbacterial meningitis, and in monitoring the clinical course of the illness. PMID- 1878963 TI - [Strategy of eliminating poliomyelitis worldwide]. PMID- 1878964 TI - [Epidemiologic study of risk factors in polio--case-control study on 117 pairs. Zhang Rongzhen and Shandong Collaboration Group of Poliomyelitis]. AB - In Oct. 1989 we carried on the case-control study on children with polio in a few years, matched with 1:1 in two districts in Shandong province. According to the results of data of 117 pairs condition logistic stepwise regression was analysed. The major risk factors on polio are: no oral poliovaccine, distance between the place of vaccination and the house hygiene knowledge, type of drinking and annual revenue of the family. It was showed in order to prevent polio, we must strengthen propaganda on hygiene knowledge and improve hygiene environment when enhancing oral polio vaccine rate increasingly. PMID- 1878965 TI - [Uses of analysis of bacterial DNA in epidemiological survey]. PMID- 1878966 TI - [An epidemiological study on HIV infection in Ruili county Yunnan Province]. AB - The study of 2530 persons in Ruili county for HIV infection showed that the high risk population were drug users and the wives of infected persons. The introvanous drug users (IVDUs) have been seriously infected by the highest rate of 67.98%. The sexual transmission male to female have occurred, and 2 out of 64 wives of infected husbands (3.13%) were affected. Seventy-five Burmese were examined and 10 (13.3%) were positives. No positive was found in other population including prostitutes, waiters and waitress of hotel, doctors, clinic patients and blood donors etc. PMID- 1878967 TI - Oncogenic conversion of transcription factors by chromosomal translocations. PMID- 1878968 TI - Induction of epithelial tubular morphogenesis in vitro by fibroblast-derived soluble factors. AB - We have designed an in vitro system in which Madin-Darby canine kidney (MDCK) epithelial cells are cocultured in collagen gels with fibroblasts under conditions precluding heterocellular contact. Using this experimental approach, we have obtained evidence that fibroblast-derived soluble factors play a crucial role in the control of epithelial morphogenesis. First, MDCK cells suspended alone in collagen gels form spherical cysts, whereas in the presence of fibroblasts they form branching tubules. Second, MDCK cells grown as a monolayer on fibroblast-containing collagen gels invade the underlying matrix, within which they form a network of tubules. Third, fibroblast-conditioned medium mimics the effects of coculture by eliciting tubulogenesis by MDCK cells. These results demonstrate the involvement of diffusible paracrine factors in morphogenetic epithelial-mesenchymal interactions and provide a strategy for their molecular characterization. PMID- 1878969 TI - Region-specific differentiation of the hippocampal stem cell line HiB5 upon implantation into the developing mammalian brain. AB - Proliferating precursors to the distinct cell types constituting the mammalian brain can be identified by the presence of the nestin intermediate filament. We report the establishment of a nestin-positive cell line, HiB5, from embryonic precursor cells to the rat hippocampus. Since it was immortalized using the temperature-sensitive allele tsA58 of SV40 large T antigen, these cells grow continuously at 33 degrees C, but not at 39 degrees C, the body temperature of rodents. To test their developmental capacity, HiB5 cells were implanted into both the neonatal hippocampus and cerebellum. The cells integrated into the host tissue and acquired morphologies characteristic of the neurons and glial cells found at the implant site. HiB5 cells might thus be useful in characterizing the signals regulating cell type determination in the mammalian brain. PMID- 1878970 TI - A novel poly(A)-binding protein acts as a specificity factor in the second phase of messenger RNA polyadenylation. AB - Polyadenylation of mRNA precursors by poly(A) polymerase depends on a specificity factor, CPF, recognizing the polyadenylation signal AAUAAA. This paper describes an apparently novel poly(A)-binding protein that acts as a second specificity factor, mediating the recognition of the growing poly(A) tail. A transition from a slow initiation phase of polyadenylation to rapid elongation occurs when the growing tail is long enough to serve as a binding site for the poly(A)-binding protein. Elongation of an RNA carrying a tail of 10 or more adenylate residues can occur independently of CPF. A sharp decrease in the poly(A) chain growth rate after the addition of approximately 200 adenylate residues invites speculations about a role of the poly(A)-binding protein in poly(A) tail length control. PMID- 1878971 TI - The act cluster contains regulatory and antibiotic export genes, direct targets for translational control by the bldA tRNA gene of Streptomyces. AB - The actII region, flanked by biosynthetic genes in the 25 kb act cluster of S. coelicolor, consists of four open reading frames, including a transcriptional activator for the biosynthetic genes, and genes controlling antibiotic export. A TTA codon (extremely rare in Streptomyces) is present both in actII-ORF2 (encoding a putative transmembrane export protein) and actII-ORF4 (the transcriptional activator gene). Change of the TTA in ORF4 to TTG reverses the normal interruption of actinorhodin synthesis caused by mutation in the pleiotropic regulatory gene bldA (which encodes the cell's tRNA(Leu)(UUA)). We conclude that initiation of actinorhodin synthesis via the actII-ORF4 product, and the final step in production, antibiotic export, are twin targets via which bldA exerts developmental control of actinorhodin production. PMID- 1878972 TI - lac repressor acts by modifying the initial transcribing complex so that it cannot leave the promoter. AB - RNA polymerase engaged in the joint complex with the lac repressor at the lac UV5 promoter cannot escape into elongation but generates abortive RNA oligomers. The joint complex actively transcribes a few initial base pairs in a reaction unusually sensitive to a decrease in the substrate concentration. The joint complex, however, fails to traverse a point in the initial transcribed sequence that normally requires a high concentration of the elongating substrate. Thus, the repressor acts by augmenting a natural high "kNTP" site (pause site) embedded in the promoter. A lethal RNA polymerase mutation that mimics the effect of the repressor leads to an analogous block of promoter clearance and shortened abortive product pattern on several promoters, reflecting the widespread occurrence of high kNTP sites in promoters. PMID- 1878973 TI - Absence of expression of the FMR-1 gene in fragile X syndrome. AB - We previously reported the isolation of a gene (FMR-1) expressed in brain at the fragile X locus. One exon of this gene lies within an EcoRI fragment that exhibits length variation in fragile X patients. This exon also contains the CGG repeat within the CpG island hypermethylated in fragile X patients. To study the involvement of the FMR-1 gene in the fragile X syndrome, its expression was studied in lymphoblastoid cell lines and leukocytes derived from patients and normal controls. FMR-1 mRNA was absent in the majority of male fragile X patients, suggesting a close involvement of this gene in development of the syndrome. Normal individuals and carriers all show expression. The methylation status of the BssHII site at the CpG island was also studied by Southern blot analysis of DNA from patients, carriers, and controls. The minority of fragile X affected males that show expression of FMR-1 demonstrated an associated incomplete methylation of the BssHII site. PMID- 1878974 TI - The effect of size of polystyrene particles on their retention within the rat peritoneal compartment, and on their interaction with rat peritoneal macrophages in vitro. AB - Polystyrene particles (size range 300 nm-3 microns diameter) were radioiodinated and their capture by rat peritoneal macrophages measured in vitro. For unmodified particles, most efficient accumulation was observed using a diameter of 600 nm (Endocytic Index (E.I.) = 16.4 +/- 2.9 microliters/10(6) cells/h). Particles (3 microns diameter) which had been modified to become more hydrophilic by hydroxymethylation showed an increased rate of capture (E.I. = 136.6 +/- 91.2 microliters/10(6) cells/h). Following intraperitoneal administration to rats, unmodified 3 micron particles showed selective accumulation in the omentum (18.4% injected dose/g), and this was increased for the hydroxymethylated bead (35.3% dose/g). The smaller (800 nm) particles were better able to leave the peritoneal compartment. Radiolabelled particles isolated from a peritoneal wash after 5 h were mostly cell-associated (72-86%, depending on the type of particle). PMID- 1878975 TI - Microinjection of intermediate filament proteins into living cells with and without preexisting intermediate filament network. AB - Human cells grown in monolayer culture were microinjected with intermediate filament subunit proteins. In fibroblasts with a preexisting vimentin network, injected porcine glial fibrillary acidic protein (GFAP) co-localized with the vimentin network within 24 hours. Phosphorylated GFAP variants were found to become dephosphorylated concomitantly with their incorporation into filamentous structures. After microinjection of either porcine GFAP or murine vimentin into human carcinoma cells lacking cytoplasmic intermediate filaments, we observed that different types of filament networks developed. Whereas vimentin was incorporated into short filaments immediately after injection, GFAP was found to aggregate into rodlike structures. This may indicate a differential filament forming ability of these intermediate filament proteins in vivo. PMID- 1878976 TI - CCCP in acidic medium and high sodium concentration causes inhibition of human neutrophil locomotion. PMID- 1878977 TI - L6 myoblast proliferation in response to muscle-derived extracts and serum from exercise-trained rats. AB - Serum and skeletal muscle-derived extracts (MDE) were bioassayed for their ability to promote [3H]thymidine incorporation in L6 myoblasts to determine if exercise-training increases mitogenic growth factor activity. Rats were trained by climbing a 60 cm vertical grid with progressively greater weight for 7 and 28 days. Serum from 7 day trained rats and vastus MDE from 7 and 28 day trained rats, but not rectus femoris MDE, had increased mitogenic activity compared to serum and MDE from untrained rats. These data suggest that exercise may increase mitogenic growth factors in some skeletal muscles. PMID- 1878978 TI - Soluble glutathione transferases in the mouse hepatoma derived established BW7756 cell line. PMID- 1878979 TI - Neural crest cell galvanotaxis: new data and a novel approach to the analysis of both galvanotaxis and chemotaxis. AB - The galvanotaxis response of neural crest cells that had migrated out of the neural tube of a 56-hr-old quail embryo onto glass coverslips was observed using time-lapse video microscopy. These cells exhibit a track velocity of about 7 microns/min and actively translocate toward the negative pole of an imposed DC electric field. This nonrandom migration could be detected for fields as low as 7 mV/mm (0.4 mV/cell length). We find that this directional migration is independent of the speed of migration and have generated a rather simple mathematical equation that fits these data. We find that the number of cells that translocate at a given angle, phi, with respect to the field is given by the equation N(phi) = exp(a0 + a1cos phi), where a1 is linearly proportional to the electric field strength for fields less than 390 mV/mm with a constant of proportionality equal to KG, the galvanotaxis constant. We show that KG = (150 mV/mm)-1, and at this field strength the cellular response is approximately half maximal. This approach to cellular translocation data analysis is generalizable to other directed movements such as chemotaxis and allows the direct comparison of different types of directed movements This analysis requires that the response of every cell, rather than averages of cellular responses, is reported. Once an equation for N(phi) is derived, several characteristics of the cellular response can be determined. Specifically, we describe 1) the critical field strength (390 mV/mm) below which the cellular response exhibits a simple, linear dependence on field strength (for larger field strengths, an inhibitory constant can be used to fit the data, suggesting that larger field strengths influence a second cellular target that inhibits the first); and 2) the amount of information the cell must obtain in order to generate the observed asymmetry in the translocation distribution (for a field strength of 100 mV/mm, 0.3 bits of information is required). PMID- 1878980 TI - Recent insights into the assembly, dynamics, and function of intermediate filament networks. PMID- 1878981 TI - A component of the interphase cytoskeleton is cyclically recruited into spindle poles during mitosis. AB - During the transition from interphase to mitosis, proteins are recruited into forming spindle poles [Leslie, Cell Motil. Cytoskeleton 16:225-228, 1990]. Antibodies which recognize these recruited components clearly label spindle poles during mitosis but the location and character of such proteins during interphase remain a mystery. Competition assays using an antibody to a recruited spindle pole protein show that in its disperse form the spindle pole protein is a highly insoluble component of the cytoskeleton which is dispersed to such an extent during interphase that it is difficult to identify by immunolocalization. The function of recruited spindle pole proteins is unknown but the aggregation/dispersion cycle and the antigen are highly conserved, appearing in sea urchin embryos and tissue culture cells. PMID- 1878982 TI - An automated assay for quantifying the swimming behavior of Paramecium and its use to study cation responses. AB - Paramecium tetraurelia is a ciliated protist that alters its swimming behavior in response to various stimuli. Like the sensory responses of many organisms, these responses in Paramecium show adaptation to continued stimulation. For quantitative studies of the initial response to stimulation, and of the time course of adaptation, we have developed a computerized motion analysis assay that can detect deviations from the normal swimming pattern in a population of cells. The motion of an average of ten cells was quantified during periods ranging from 15 to 60 seconds, with a time resolution of 1/15 seconds. During normal forward swimming, the maximum deviation from a straight-line path was less than 17 degrees. Path deviations above this threshold value were defined as changes in swimming direction. The percentage of total path time that cells spent deviating from forward swimming was defined as percent directional changes (PDC). This parameter was used to construct dose-response curves for the behavioral effects of various externally added cations known to induce behavioral changes and also to show the time course of adaptation to a depolarizing K+ stimulus. This assay is a valuable tool for studies of chemoeffectors or mutations that alter the swimming behavior of Paramecium and may also be applicable to other motile organisms. PMID- 1878983 TI - Effects of interferon-beta on the translocation rate and stationary time in human fibroblasts in culture. AB - The rate of translocation and the percent of the time that cells are stationary have been measured by computer-assisted time-lapse cinemicrography in over 1,000 freshly planted human foreskin fibroblasts (FS-4 cell strain) for periods of up to a week and the effects of interferon-beta (IFN-beta) on these parameters have been determined. Cells were planted at 2.5 X 10(3) cells/cm2 in Eagle's minimal essential medium (MEM) with 10% fetal bovine serum (FBS). Frames were taken every 2 or 4 minutes and data were collected on both cell location and cell division as a function of time. After planting FS-4 cells require approximately 48 hr to reach maximum motility both with respect to the translocation rate when moving and percent time cells are moving. Recombinant human INF-beta (800 mu/ml) caused a marked increase in the fraction of time cells were stationary and a decrease of lesser magnitude in the translocation rate, as quantitated during the period during which the stationary fraction for control cells was at a minimum. IFN-beta also decreased the rate of cell proliferation, without any evidence of degeneration or death of cells. Our results contribute new evidence that the fraction of time cells spend moving directionally is an important determinant of their locomotory behavior and that this determinant is responsive to modulation by cytokines. PMID- 1878984 TI - Beta VLDL uptake by pigeon monocyte-derived macrophages: correlation of binding dynamics with three-dimensional ultrastructure. AB - Endocytosis of pigeon beta migrating very-low-density lipoprotein (beta VLDL) by monocyte-derived macrophages (monocyte/macrophages), cultured from Random Bred White Carneau (RBWC) pigeons, occurs by both coated and non-coated regions of the plasma membrane (Henson et al.: Exp. Mol. Pathol. 51:243-263, 1989). Secondary to binding, the beta VLDL is translocated to lysosomes for degradation. Ultimately these events lead to foam cell formation in vitro. Utilizing video-enhanced contrast light microscopy in conjunction with whole mount intermediate-voltage transmission electron microscopy (IVEM) and high-resolution scanning EM, the dynamics of beta VLDL binding have been correlated with ultrastructure. Beta VLDL conjugated to gold colloids was visualized at the surface of living cells by using Allen video-enhanced contrast-differential interference contrast microscopy (AVEC-DIC). Subsequent to AVEC-DIC, direct observation of the identical cells by IVEM and SEM was facilitated through the use of gold finder grids, and these EM observations confirmed identification of the video-observed beta VLDL particles. Upon addition of beta VLDL, pigeon monocyte/macrophages underwent gross morphological changes. These changes were recorded by video as movements at the cytoplasmic periphery, and the movements involved extension of microvilli, expression of retraction fibers, and elaboration of membrane ruffles. When secondarily observed by stereo (3-D) IVEM and SEM, the identification of microvilli, retraction fibers, and membrane ruffles was confirmed and the lipoprotein-gold conjugates were associated with these ligand-induced membrane structures. Beta VLDL-gold conjugates were also associated with pit-like regions at the base of microvilli, while at the base of ruffles, beta VLDL-gold conjugates were located in membrane invaginations and cytoplasmic vesicles. PMID- 1878985 TI - Pseudopodial activity at the active edge of migrating fibroblast is decreased after drug-induced microtubule depolymerization. AB - It is known that depolymerization of microtubules by colcemid or other similar drugs abolishes polarization of pseudopodial activity in migrating fibroblasts. In this work the effect of colcemid on the intensity of protrusion and retraction of lamellipodia at the active edges of human fibroblasts migrating into the wound was investigated with video-enhanced contrast microscopy. To characterize the pseudopodial activity quantitatively the outlines of the active edges in the pairs of frames taken at adjacent 20-sec intervals were compared and mean areas of protrusions and retractions per unit length of the perimeter of the edge were measured. The mean rates of protrusions and retractions were 4-6 times less in colcemid-treated cells than in controls. Thus, microtubules depolymerized by colcemid, and/or intermediate filaments undergoing perinuclear collapse in the presence of this drug, are essential not only for the restriction of pseudopodial activity to one particular zone of the cell edge but also for the development of maximal activity in this zone. PMID- 1878986 TI - A quantitative study of the role of F-actin in producing neutrophil shape. AB - Neutrophils change shape from round to polar and sequentially polymerize/depolymerize actin following chemotactic peptide activation in suspension. To study the relationship between changes in F-actin content and shape we altered the kinetics/extent of actin polymerization and depolymerization with tBOC peptide, cytochalasin D (CD), and low-dose FMLP, and determined the effect of these alterations on the temporal sequence of changes in neutrophil shape. F-actin was measured by FACS analysis of NBDphallacidin-stained cells and expressed as relative fluorescent intensity (RFI) compared to control (RFI = 1.00). Shape was determined by scanning electron microscopy. FMLP causes serial polymerization/depolymerization of actin (RFI = 1.00 +/- 0.04, 1.60 +/- 0.21, 1.10 +/- 0.18, and 1.05 +/- 0.14) associated with four distinct shapes (round smooth, round-ruffled, blebbed, and polar) noted at 0, 30, 90, 300 sec respectively. Since blebbed and polar shapes appear concurrent with depolymerization and following polymerization, we determined whether depolymerization is required for polarization of cells. The kinetics of depolymerization were: (1) accelerated by tBOC addition at 45 sec, and (2) slowed by high concentrations of FMLP (greater than 10-7M) (300 sec RFI = 1.46). Neither change altered the time course of shape change. To determine whether duration of actin polymerization defines shape, polymerization was halted by addition of tBOC at 5, 10, 20, 30 sec after FMLP to block actin polymerization and shape was monitored at 300 sec. TBOC added 5-20 sec after FMLP limited neutrophil shape change to the blebbed form, while tBOC addition 30 sec following FMLP resulted in a polar shape at 300 sec. To determine whether the extent of actin polymerization affects the shape change sequence, polymerization was limited by (1) inhibition of polymerization with CD, (2) exposure of cells to low concentrations of FMLP (less than 10-9 M), and (3) interruption of polymerization with tBOC. Actin polymerization to RFI less than 1.35-fold basal results in blebbed shape; polymerization greater than 1.35-fold basal yields polar shape. The data show: (1) the human neutrophil demonstrates intermediate shapes when activated by chemotactic peptide, (2) depolymerization of F-actin does not determine shape, and (3) blebbed shape appears when actin polymerizes for greater than 5 sec; polar shape with polymerization greater than or equal to 30 sec to RFI greater than 1.35-fold basal. The data suggest actin polymerization is required for, and extent of polymerization determines, the shape of human neutrophils. PMID- 1878987 TI - Discrete subcellular localization of a cytoplasmic and a mitochondrial isozyme of creatine kinase in intestinal epithelial cells. AB - Two isozymes of creatine kinase have been purified differentially from mitochondrial and cytoplasmic subfractions of intestinal epithelial cells. These intestinal epithelial cell creatine kinases were indistinguishable from the cytoplasmic (B-CK) and mitochondrial (Mi-CK) creatine kinase isozymes of brain when compared by SDS-PAGE, cellulose polyacetate electrophoresis, and peptide mapping. In intestinal epithelial cells, immunolocalization of the Mi-CK isozyme indicates that it is associated with long, thin mitochondria, which are excluded from the brush border at the apical end of each cell. In contrast, immunolocalization of the B-CK isozyme indicates that it is concentrated distinctly in the brush border terminal web domain. Although absent from the microvilli, B-CK also is distributed diffusely throughout the cytoplasm. Terminal web localization of B-CK was maintained in glycerol-permeabilized cells and in isolated brush borders, indicating that B-CK binds to the brush border structure. The abundance and localization of the mitochondrial and cytoplasmic creatine kinase isozymes suggest that they are part of a system that temporally and/or spatially buffers dynamic energy requirements of intestinal epithelial cells. PMID- 1878988 TI - Metabolic regulation in mammalian sperm: mitochondrial volume determines sperm length and flagellar beat frequency. AB - In the absence of glycolytic support, mammalian sperm derive their energy for motility from a densely packed array of mitochondria at the base of the flagellum known as the midpiece. Using data on the morphometric dimensions of over 200 mammalian species, we found that an allometric relationship exists between midpiece length (Lm) and flagellum length (Lf). Specifically, the length of the mid-piece varies approximately as the 3/2 power of the flagellar length although the proportionality constant is different for eutherian and marsupial sperm. In contrast, when we corrected for the fraction of the midpiece that was taken up by mitochondria, a single linear correlation between mitochondrial volume and flagellar length for all mammals was found. These allometric relationships were used along with basic flagellar hydrodynamic theories to establish a unifying equation that predicted flagellar frequencies for any mammalian sperm between 40 microns and 200 microns in length. These findings imply that, at least in mammals, the mechanisms for energy production and dissipation in sperm flagella are highly conserved. PMID- 1878989 TI - Subcellular compartmentalization of myosin isoforms in embryonic chick heart ventricle myocytes during cytokinesis. AB - Embryonic chick heart ventricle myocytes retain the ability to alternate between proliferation and functional differentiation. A cytoplasmic isoform of myosin is present in cleavage furrows of various nonmuscle cells during cytokinesis, whereas one or more of the cardiac myosin isoforms are localized in sarcomeres of beating cardiomyocytes. Antibodies were employed to reveal the subcellular localizations of cytoplasmic and cardiac myosin isoforms in embryonic chick ventricle cardiomyocytes during cytokinesis. Monoclonal anticytoplasmic myosin antibodies were prepared against myosin purified from brains of 1-day-posthatched chickens and shown to react with chick brain myosin heavy chain by Western blots and/or ELISA tests. One monoclonal antibrain myosin antibody also cross-reacted with chick cardiac myosin but not with skeletal or smooth muscle myosins. Two antichick cardiac myosin monoclonal antibodies and one antichick skeletal myosin polyclonal antibody that cross-reacts with cardiac myosin were employed to identify cardiac sarcomeric myosin. Cells were isolated from day 8 embryonic chick heart ventricles, enriched for myocytes, grown in vitro for 3 days, and then examined by immunofluorescence techniques. Monoclonal antibodies against cytoplasmic myosin preferentially localized in the cleavage furrows of both cardiofibroblasts and cardiomyocytes in all stages of cytokinesis. In contrast, antibodies that recognize cardiac myosin were distributed throughout cardiomyocytes during early stages of cytokinesis, but became progressively excluded from the furrow area during middle and late stages of cytokinesis. These data suggest that in cells that contain both cytoplasmic and sarcomeric myosin isoforms, only cytoplasmic myosin isoforms are mobilized to from the contractile ring for cytokinesis. PMID- 1878991 TI - [The effect of piperidinoethylesters of n-alkoxyphenyl-carbamic acids on bacterial cells]. AB - The inhibitory effect of local anaesthetic agents of this type on the bacteria Escherichia coli were evaluated. The dependence between antimicrobial activity and structure (log 1/MIC = f/m) was studied with the use of a bilinear model. In the positional paraisomers a lower effect of spherical and electron effects than in the case of ortho- and meta-isomers is assumed. The efficacy of these agents depends on their lipophilicity. Membrane activity of these agents was confirmed. In subinhibitory concentrations they cause leakage of cytoplasmic material lysis of spheroplasts, they increase the permeability of the membrane for protons and inhibit dehydrogenase activity of cells. The mode of action of heptacainium chloride and its positional isomers on cells is identical and is similar as in organic ammonium salts and amine oxides. PMID- 1878990 TI - Unidirectional microtubule assembly in cell-free extracts of Spisula solidissima oocytes is regulated by subtle changes in pH. AB - Most, if not all, microtubules in vivo grow unidirectionally from a nucleation site such as the centrosome. This organized growth of microtubules can generate and maintain the radially symmetrical array of interphase microtubules as well as the bipolar mitotic apparatus. To investigate the regulation of polarized microtubule growth, we have prepared a cell-free extract from surf clam oocytes that exhibits unidirectional microtubule assembly. Immunofluorescence microscopy was used to visualize the net assembly of microtubules onto the fast (plus)- and slow (minus)- growing ends of isolated ciliary axonemes. All detectable microtubule growth in these cytoplasmic extracts occurred at the plus (+) ends and the extent of (+) end growth was regulated by subtle changes in pH. Microtubule assembly in these crude extracts was highly favored at pH 7.3, the pH of the post-fertilization cytoplasm. In contrast, when tubulin was purified from these oocyte extracts, integral components were lost, and microtubule growth became predominantly bidirectional and was favored at acidic pH. These results indicate that cytoplasmic factors may inhibit bidirectional growth in vivo and that temporal or local changes in cytoplasmic pH may influence microtubule assembly during the cell cycle. PMID- 1878992 TI - [Determination of Lonazolac in blood using liquid chromatography with fluorescence detection and use of this method in a comparison of Lonazolac Irritren preparations]. AB - An analytical method was worked out to determine Lonazolac in human plasma based on precipitation of human plasma with a precipitating agent and methanol. This deproteinized plasma was analyzed by liquid chromatography with the use of a reverse phase and fluorimetric detection. The described method is sufficiently sensitive (the limit of detection under 0.1 microgram/ml of plasma) and precise (error of the method = 9%). The precision of the method, recovery from the plasma (100 +/- 3%) and stability in frozen plasma (minimally one month) are presented. Application of the method in a comparison of the newly developed Czechoslovak preparation Lonazolac and the foreign preparation Irritren is shown. Results are documented by the course of the levels of both preparations in dependence on time and principal pharmacokinetic parameters derived from the one-compartmental model. PMID- 1878993 TI - [Densitometric determination of piroxicam in plasma]. AB - Piroxicam was extracted from acid medium into chloroform and isolated on a thin layer of silica gel with the use of the system chloroform - absolute ethanol - benzene - aqueous ammonia (20:15:15:0.5). The intensity of fluorescence of stains was measured densitometrically (an Hg lamp, a filter FL - 39, 330 nm). The limit of detection of the stain is 0.020 microgram/ml of plasma. PMID- 1878994 TI - [Advances in the laboratory diagnosis of diseases of the thyroid gland. III. Determination of free thyroxine and "ultrasensitive" determination of TSH]. PMID- 1878995 TI - Hyper-resistance to nitrogen mustard in Saccharomyces cerevisiae is caused by defective choline transport. AB - The recessive hnm1 mutant allele is responsible for hyper-resistance to nitrogen mustard in Saccharomyces cerevisiae. Transformation with a single-copy HNM1 wild type allele of such hyper-resistant mutants will restore wild-type sensitivity to nitrogen mustard. By contrast the presence of multi-copy vectors containing HNM1, in either a hyper-resistant hnm1 mutant or an HNM1 wild-type, will lead to a novel, mustard-sensitive phenotype unrelated to defects in DNA repair genes. Gene disruption of HNM1 revealed that this gene is non-essential for cells prototrophic for choline (CHO1) but lethal for cells with a cho1 genotype. Sensitivity to nitrogen mustard of wild-type HNM1, but not of hnm1 mutants, depends on the choline content of the growth medium, with cells grown in choline free medium exhibiting the highest sensitivity. Sequencing of a 300 bp DNA fragment of HNM1 revealed the identity of this gene with the CTR locus, which is responsible for choline transport in Saccharomyces cerevisiae. PMID- 1878997 TI - Synchronized meiosis and recombination in fission yeast: observations with pat1 114 diploid cells. AB - The mutation pat1-114 has been used to synchronize meiosis in the fission yeast Schizosaccharomyces pombe. We have investigated several aspects of such synchronized meiotic cultures. In both pat1-114 and pat1+ diploids, meiotic landmark events are initiated at the same time after meiosis induction, but synchrony is much more pronounced in the pat1-114-driven meiosis. Commitment to recombination and to meiosis have been timed at 2 h after meiotic induction. Due to a seven-fold reduction of intragenic recombination frequency in the ade6 region of pat1-114 diploids, physical analysis of recombination has not been possible. We have distinguished three factors that influence intragenic recombination frequencies: temperature, azygotic versus zygotic meiosis, and the nature of the pat1 allele. Differences and similarities in the timing of meiotic landmarks in S. cerevisiae and S. pombe are discussed. PMID- 1878996 TI - The SNQ3 gene of Saccharomyces cerevisiae confers hyper-resistance to several functionally unrelated chemicals. AB - A multi-copy plasmid containing the SNQ3 gene confers hyper-resistance to 4 nitroquinoline-N-oxide (4NQO), Trenimon, MNNG, cycloheximide, and to sulfometuron methyl in yeast transformants. Restriction analysis, subcloning, and DNA sequencing revealed an open reading frame of 1,950 bp on the SNQ3-containing insert DNA. Gene disruption and transplacement into chromosomal DNA yielded 4NQO sensitive null mutants which were also more sensitive than the wild-type to Trenimon, cycloheximide, sulfometuron methyl, and MNNG. Hydropathic analysis showed that the SNQ3-encoded protein is most likely not membrane-bound, while the codon bias index points to low expression of the gene. PMID- 1878998 TI - Antisuppressor mutations reduce misreading of the genetic code in Aspergillus nidulans. AB - Antisuppressor mutations were isolated in a strain containing the omnipotent suppressor suaC109. The antisuppressors reduce the activity of translational suppressors in vivo and counteract most aspects of the pleiotropic phenotype associated with the suaC and the suaA suppressor mutations. Using an homologous system for cell-free translation, we have measured translational accuracy in two antisuppressor strains with the genotype suaC109 and either the asuB11 or the asuD14 antisuppressor mutation. Ribosomes from antisuppressor mutants have higher levels of translation accuracy than those from the suppressor strain (suaC109, asu+). Mistranslation levels depended solely on the source of the sucrose-cleaned ribosomes. However, the increased accuracy associated with sucrose-cleaned ribosomes from antisuppressor strains can be nullified by salt-washing, suggesting that the component responsible can be washed off. PMID- 1878999 TI - Expression and sequence comparison of the Aspergillus niger and Aspergillus tubigensis genes encoding polygalacturonase II. AB - The structure and expression of the polygalacturonase-encoding pgaII genes of two recently recognized species, Aspergillus niger and Aspergillus tubigensis, was investigated. While the structure of the pgaII genes is very similar, showing 83% DNA sequence identity and 94% identity at the amino acid level, they have diverged significantly. The NH2-terminal sequence suggests that these PGs are made as pre pro-proteins and the secretory propeptide of the PGII precursors shows sequence homology with some other fungal pro-peptides. The expression of the pgaII genes is strongly regulated by the carbon source and the A. tubigensis gene is expressed and regulated in A. niger transformants. The low similarity of the fungal PGs with those of bacterial and plant origin is discussed in relation to the possible functional role of specific amino acids. PMID- 1879000 TI - Isolation, characterization and sequence of a gene conferring resistance to the systemic fungicide carboxin from the maize smut pathogen, Ustilago maydis. AB - A gene which confers resistance to the systemic fungicide carboxin (Cbx) has been isolated from the maize pathogen, Ustilago maydis, by transferring a plasmid gene library from a Cbx-resistant mutant strain into a sensitive strain and selecting for expression of the resistance gene. Five plasmids, rescued from transformants which exhibited enhanced resistance to Cbx, were shown to have DNA inserts with common restriction enzyme fragments. All the plasmids transformed a sensitive U. maydis strain to Cbx resistance. The gene (Cbxr), sub-cloned on a 3.2 kb EcoR1 HindIII fragment, transformed U. maydis to Cbx resistance at frequencies similar to those obtained with the bacterial Hygromycin B resistance (HygBr) gene. The sequence of the Cbxr gene showed a high degree of homology to succinate dehydrogenase (EC 1.3.99.1) iron-sulphur subunit genes from other organisms. PMID- 1879001 TI - Homology between mitochondrial DNA of Agaricus bisporus and an internal portion of a linear mitochondrial plasmid of Agaricus bitorquis. AB - Agaricus bisporus, the cultivated mushroom, contains a mitochondrial fragment (50H) which was previously demonstrated by Southern hybridization to have sequence similarity to an internal region of pEM, a linear mitochondrial plasmid of Agaricus bitorquis. The nucleotide sequence of 50H was determined and compared to the sequence of the corresponding pEM fragment. The region of sequence homology on pEM is contained within an open reading frame (ORF) that may encode an RNA polymerase, but 50H is neither an intact nor a complete copy of the ORF. pEM also contains an ORF with characteristics of genes for virus-encoded DNA polymerases. pEM appears to be very similar to other linear mitochondrial plasmids (in fungi and higher plants) reported to contain ORFs that may encode the same types of polymerases. The potential functionality of the pEM sequence suggests that it has diverged less than the mitochondrial fragment from a common ancestor. PMID- 1879002 TI - Evidence for multiple xenogenous origins of plastids: comparison of psbA-genes with a xanthophyte sequence. AB - When only plastidic features are considered, it is difficult to distinguish between monophyletic and polyphyletic xenogenous origins of plastids. We suggest that a direct comparison of nuclear and plastidic sequence-similarity pattern will help to solve this problem. The D1 amino acid sequence of six major groups of photosynthetic eukaryotes and of the two groups of photosynthetic prokaryotes are now available, including the psbA-gene product from Bumilleriopsis filiformis, which is the first molecular sequence reported for a xanthophycean alga. Evidence is provided for an independent and polyphyletic origin of plastids from five out of the six major taxa of photosynthetic eukaryotes. This conclusion is reached by comparing a plastid-based pattern of D1 similarity with a nucleus based similarity pattern published recently. Furthermore, the availability of D1 sequences from five eukaryotic algae led to a re-evaluation of the taxonomic position of Prochlorothrix. PMID- 1879003 TI - [The profile of T-lymphocyte subsets' populations in 4 different kinds of pulmonary disorders]. AB - By using the bronchoalveolar lavage (BAL) technique, the authors observed the distribution of T-lymphocyte subsets both in peripheral blood and BAL fluid from 4 different kinds of pulmonary disorders (44 cases). It was shown that the percentage of lymphocytes in BAL fluid was increased, the CD+3 and CD+4 cells were elevated and 4/8 ratio was also significantly elevated in the sarcoid patients (11 cases); the CD+4 cells decreased but the CD+8 cells increased and the 4/8 ratio decreased significantly in the patients of idiopathic pulmonary fibrosis (7 cases) and the patients with thoracic malignant tumors (20 cases). This special profile of T-lymphocytes indicates that the cell-mediated immune function may play an important role in the pathogenesis of the above illnesses. PMID- 1879004 TI - [Preliminary observation on lymphocyte function with radioisotope incorporation in asthmatic patients]. AB - Twenty-five asthmatic patients and 54 normal subjects were included in this study. The results of our study showed that among the asthmatic group, no obvious decrease was observed in the uptake of 3H-TdR by T-lymphocyte stimulated with PHA, whereas there was markedly depressed uptake of 14C-UR by T-lymphocyte. The latter finding demonstrated that the asthmatic patients had a decrease of RNA synthesis during the course of T-lymphocyte transformation. The mean 3H-TdR uptake by T-lymphocyte was less in the patients whose first attack of asthma occurred after 30 years of age, when compared to those before 30 years of age, but statistically not significant. There was a slightly lower uptake of 3H-TdR by T-lymphocyte in the mild attack group than that in the remission group. B lymphocyte transformation ability reflected in the uptake of 3H-tyrosine by B lymphocyte stimulate with LPS was apparently increased in the asthmatic group, as compared to normal subjects. This study supports the hypothesis that the abnormal function of cell-mediated immunity may play a role in the pathogenesis of asthma. PMID- 1879005 TI - [The nature of chronic asthmatic bronchitis]. AB - In order to study the nature of chronic asthmatic bronchitis, we compared the clinical features of patients with chronic asthmatic bronchitis, bronchial asthma and simple chronic bronchitis. We also measured FEV1 on these patients before and after inhaling 1% isoproterenol aerosol as well as after administration of oral prednisone (40 mg/day) for a week. The results showed that there was little difference in terms of precipitating factors, attacking features, premonitory symptoms, developing course and relieving measures between the patients with chronic asthmatic bronchitis and bronchial asthma. The improved percentage of FEV1 (more than 15%) on the patients with chronic asthmatic bronchitis after inhalation of bronchodilator aerosol and administration of oral prednisone showed no significant difference from that of bronchial asthma. We suggest that the former term be replaced by the term of chronic bronchitis associated with asthma. It can probably avoid the confusion on the diagnosis of chronic bronchitis and bronchial asthma. PMID- 1879006 TI - [Drug monitoring in the treatment of 72 patients with aminophylline]. AB - The drug monitoring of serum concentration of Aminophylline by means of HPLC and FPIA to 72 patients suffering from bronchial asthma and asthmatic bronchitis; the relations among the quantities, serum drug concentrations, effects and side effects of Aminophylline were reported. The results showed that it is necessary to take Aminophylline individually under the guide of drug monitoring. The monitoring should be combined with clinical observation and comprehensive treatment of the diseases. The major values of effective serum concentration of Aminophylline range from 8 to 20 mg/L, while above the value of 20 mg/L, its side effects will significantly increase. It is safe and effective for asthmatic adult patients (over 55 Kg weight) if the oral dose of Aminophylline is not more than 200 mg Q8h, or for others with continuous asthmatic attacks to be given with 250 mg of Aminophylline intravenously in drip followed by oral dose of the drug 200 mg Bid. PMID- 1879007 TI - [CT diagnosis in primary lung cancer (a correlative study of roentgenogram CT, surgical and pathological findings)]. AB - A correlative study of roentgenogram, CT, surgical and pathological findings was investigated on 40 cases with primary lung cancer to evaluate differences between x-ray and CT of the chest in imaging pathological changes of lung cancer. The study revealed that CT was more sensitive than roentgenogram in showing lobulation, speculate and internal structure of SPN or masses, hilar and mediastinal adenopathy, invasion to neighbouring tissues and soft tissues of chest wall and abnormal pattern of the bronchus in cross section. Abnormal findings in CT was 67.4% higher than that in roentgenogram, CT provided more information in diagnosis of primary lung cancer. Some limitations of CT in diagnosis of primary lung cancer were also discussed. PMID- 1879008 TI - [A study on the problems of the radiologic manifestations in sarcoidosis]. AB - Unilateral hilar adenopathy, which is considered as an atypical manifestation of sarcoidosis, appeared only on the initial stage, and eventually became bilateral. The adenopathy may occur in all groups of the mediastinal lymph nodes. The roentgenological findings of the pulmonary parenchymal lesions include interstitial, alveolar, miliary and fibrous lesions. The alveolar involvement, and the pathological consideration of pseudoalveolar manifestations in X-ray film were discussed. PMID- 1879009 TI - [Application and examination of bioluminescent technique in the quality identification of BCG vaccines]. AB - (1) The average viable rates of BCG Vaccines (Japan Strain/Danmark Strain) which were kept at 37c for 4 weeks were 69.4% and 57.8% respectively by BL method, while the average viable rates of the same BCG Vaccines were obtained to be 16.8% and 21.7% by CFU method. The coefficients of variation (CV) in the average viable rates of BCG vaccines were found to be 6.6% and 6.4% by BL method, while the CV were found to be 13.7% and 36.5% by CFU method. (2) The clinical immunization effects showed the positive transformation rates of skin test were 90.9% and 88.9% (P greater than 0.05) in the control group and test group by PPD check respectively. It indicated that there was no distinct difference. Because the test group was immunized with the BCG vaccine qualified only by BL method, clinical immunization effects were conformed with the detecting results of BL method. PMID- 1879010 TI - [Severe pulmonary tuberculosis and multiple organ failure]. AB - Thirty four cases of severe pulmonary tuberculosis complicated by multiple organ failure were reported. The failure usually started firstly from the lung (70.6%). The various organ failures occurred successively to the heart, brain, liver, kidney, stomach and intestines. The death rate is 58.8 percent. The standard of diagnosis and the measures of prevention and treatment were suggested. PMID- 1879011 TI - [Advances in the treatment of pneumothorax with pleural adhesion therapy]. PMID- 1879012 TI - [Clinico-pathological analysis of 100 autopsy cases of massive or submassive pulmonary thrombo-obstruction in cardiovascular and pulmonary diseases]. AB - A clinico-pathological analysis of 100 autopsy cases of thrombo-obstruction in the segmental and those bigger arteries of the lungs caused by cardiovascular and pulmonary disease was reported. These complications of pulmonary thrombosis and/or embolism were more commonly observed in rheumatic heart disease (29% of the same disease in autopsies), congestive cardiomyopathy (26%) and cor pulmonale (19%). There were 2-4% of the autopsy cases of other cardiovascular and pulmonary diseases. The pulmonary thrombo-obstruction and/or infarction were more frequent in right lower lobes of the lungs and they were often multiple. The pulmonary infarction occurred in 76% of these cases. 35% of 100 cases occurred with sudden death. Only 13% of 100 patients with pulmonary thrombosis and/or embolism were diagnosed before autopsy. The causes of pulmonary thrombo-obstruction and the diagnostic suggestion were discussed in this paper. PMID- 1879013 TI - [Prediction of one second forced expiratory volume after lung resection using multiple view lung perfusion images and "regions of interest" quantitative analysis]. AB - In 17 patients mostly with bronchial carcinoma undergoing pneumonectomy (N = 2) or lobectomy (N = 15) multiple view lung perfusion images with 99mTc-MAA and "regions of interest" quantitative analysis of functional distributions to each lung or lobe (MV-ROI) were used for predicting postoperative FEV1. For comparison, other two methods were also conducted, i.e. the split function study by lung perfusion images combined with subtraction of segmental function (SF+SS) and the simple subtraction of segmental function (SSS). The correlation between predicted postoperative FEV1 and actual FEV1 measured 3-6 months after lung resection was better by MV-ROI method than by the other two. In all patients the correlation coefficient (r) was 0.957, 0.923 and 0.887 by three methods respectively; in lobectomy patients the (r) was 0.948, 0.907 and 0.869 by three methods respectively (all P less than 0.001). The mean error (liters), mean percent error and median of percent error between predicted and observed FEV1 in MV-ROI were less than in SF+SS or SSS. The difference between error of MV-ROI and error of SF+SS or SSS was significant, while the difference between error of SF+SS and error of SSS was insignificant. The number of cases having the error greater than 10% was 3,5,8 in all patients and 3,5,7 in lobectomy patients by three methods respectively. There was a tendency of overestimation in MV-ROI, which was attributed to the old age of our patients whose pulmonary functions recovered slowly and to the short period of the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879014 TI - [Effects of inhaled prostaglandin E1, salbutamol and verapamil on the bronchial reactivity in asthmatics]. AB - After inhaling prostaglandin E1(PGE1) by 10 asthmatic patients, the FEV1 and V50rose significantly. The bronchial reactivity reduced markedly, which was not related to the improvement in the FEV1. The bronchodilatation and effect of PGE1 on bronchial reactivity were similar to those of salbutamol. PMID- 1879015 TI - [Diaphragmatic fatigue and respiratory failure in patients with chronic obstructive pulmonary diseases]. PMID- 1879016 TI - [Measurement of fluidity of membrane lipids in lymphocytes from patients with pulmonary tuberculosis]. AB - The degree of fluidity of cellular membranes was determined by fluorescence polarization analysis using fluorescent probe 1,6-Dipheny-1,3,5-hexatriene (DPH), when embedded in membrane lipid region of intact cells. Results have shown that lymphocytes isolated from patients have a more fluid lipid layer in their cellular membrane (eta = 2.69 +/- 0.77 poise chi +/- s) than lymphocytes isolated from normal health (eta = 3.11 +/- 0.95 poise chi +/- s)(P less than 0.05). Increase in degree of membrane microviscosity was closely correlated with the rise in cells number. PMID- 1879017 TI - [Differential diagnosis between tuberculosis and cancer of lung. Analysis of 65 tuberculosis cases diagnosed by fiber-bronchoscopy]. AB - A series of 65 broncho-pulmonary TB simulating lung cancer with negative AFB in sputum were diagnosed by fiber-bronchoscopy. 60% of the cases were at the age of forty and over. According to the radiographic features, they could be divided into 3 varieties: (1) 31 cases showed mass or nodal shadow. 7 of the 11 cases with cavities mimicked cancer origin in appearance. (2) 30 cases showed atelectasis and segmental shadows with 16 cases in nonpredisposing location of TB. (3) 4 cases with diffuse interstitial and micronodular shadows were different from miliary TB. Of a total of 65 cases, 7 accompanied with hilar/mediastinum adenopathy. Using fiber-bronchoscopy, bronchial lesions were found in 24 cases (36.9%). TB diagnosed by pathological and bacteriological examination were 89.2% and 32.2% respectively. TB combined with squamous cell cancer of the lung was found in one patient. These data indicated that TBB and TBLB provided an effective method in the differential diagnosis of TB and cancer of lung. PMID- 1879018 TI - [Evaluation of administrative practices for the registration of outpatients with pulmonary tuberculosis]. AB - In this paper, the register state, regular therapy rate and sputum conversion rate for outpatients have been analysed. 30.5% of outpatients from other region were not registered. In these patients, regular therapy rate and sputum conversion rate were 10.9% and 53.7%, respectively. Comparing with above data, there were 97.3% and 96.8% for above 2 parameters in outpatients of Changhun region, 40.2% and 61.7% in outpatients of other region with register, under the management or control by hospital. PMID- 1879019 TI - [Miliary tuberculosis. Report of 4 cases proved by autopsy]. AB - Four cases of acute miliary tuberculosis, including one case of nonreactive tuberculosis, are reported in this article. Final diagnoses were proved by autopsy. Literature review shows that symptoms of the disease vary greatly in different cases, but fever with unknown causes and overwhelming infection is the constant features. Nonreactive tuberculosis is common in the patients with low immunity and correct diagnosis depends on autopsy in most cases. Anti tuberculosis drugs for nonreactive tuberculosis is not very effective and the prognosis is unfavourable. This article provides for the doctors with the experience of mis-diagnosis of acute miliary tuberculosis, especially nonreactive tuberculosis. PMID- 1879020 TI - [The effects of passive smoking on health]. AB - Our experiments were conducted on rabbits. In order to study the effects of passive smoking on the health, smokers were exposed to cigarette smoke for 30 days. Cigarette dosimetry is equivalent to two packs per day in man. The experimental results as follows. 1. There is a significant amount of Cotinine (0.69 microgram/ml) in the blood of passive smoking rabbits. 2. There is a lot of Benzpyrene (0.59 microgram/ml) in the BALF of passive smoking rabbits. 3. The level of histamine in BALF increased more than that of control group. 4. The level of TXB2 increased and the level of 6-keto-PGF1 alpha decreased in the blood of passive smoking rabbits more than that of the control group. 5. The level of elastase in the blood and the O2- production of alveolar macrophages of passive smoking rabbits are more than that of the control group. These results showed that passive smoking may increase the occurrence and development of COPD and cardiovascular disease as well. PMID- 1879021 TI - [Frequency of seroreactors to Legionella among the patients with pulmonary infections]. AB - A prospective study was conducted with patients with pulmonary infections who were consecutively admitted to the three community hospitals in Benghu from July 1986 to May 1987, and to the children's hospital in Nanjing from September 1986 to January 1987. Antibodies to Lpi-8, Lm, Ld, and Lg were measured by the micro agglutination test. During the study period, 150 adult patients (100 pairs sera) and 212 control healthy people and 110 pairs sera of childhood patients and 173 children without respiratory tract infections were investigated. The diagnosis of legionellosis was based on seroconversion (fourfold rise in titer to greater than 1:32 or static titer of greater than 1:32) and clinical and radiographic features of legionnaires' disease. About 11% legionella infection in hospitalized adult patients with pulmonary infections, and about 5.45% in children with atypical pneumonias. PMID- 1879022 TI - [Pulmonary artery pressure estimated by Doppler echocardiography in patients with chronic obstructive pulmonary disease]. AB - Doppler echocardiography and right heart catheterization were performed in 18 patients with COPD. The pulmonary blood flow pattern were analysed by the pulsed doppler flowmeter. The pulmonary artery acceleration time (PAT) showed significant inverse correlation with pulmonary artery mean pressure (mPAP) (r = 0.84, P less than 0.001) and pulmonary artery systolic pressure (sPAP) (r = 0.89, P less than 0.001). In fifteen of 18 patients, continuous wave doppler could be used to measure the maximal velocity of the regurgitant jet through the tricuspid valve (Vmax), and the right ventricle to the right atrium pressure gradient (PG) was calculated by means of simplified bernoulli equation (PG = 4V2max). PG correlated well with sPAP (r = 0.89, P less than 0.001) and mPAP (r = 0.92, P less than 0.001). We considered that doppler echocardiography was useful for noninvasive estimation of pulmonary artery pressure in patients with COPD. PMID- 1879023 TI - [Research on impedance pulmonary rheogram for calculating pulmonary artery mean pressure]. AB - A simultaneously comparative study of IPR and right catheter examination for measurement of PAMP has been done on 71 patients with COPD. The results show that the similar average value of PAMP of the examined group could be calculated by any representative equation, but at present time, an accurate predetermining value of PAMP can not be obtained by any noninvasive technique for each individual patient with COPD who has pulmonary hypertension of mild to moderate degree. PMID- 1879024 TI - [Inspiratory muscle strength and endurance in patients with chronic obstructive pulmonary disease]. AB - The maximal inspiratory pressure (MIP) and the sustainable inspiratory maximal pressure (SIPm) in 79 patients with chronic obstructive pulmonary disease (COPD) which were divided into the mild group (MG) and the mid-severe group (MSG) were measured. The results showed that MIP and SIPm were significantly lower in MSG than the prediction and in MG, the inspiratory fatigue in MSG was taken place in lower load and shorter time. We considered: MIP and SIPm fallen significantly in COPD patients might play a very important role in developing patients' respiratory failure. PMID- 1879025 TI - [The hemodynamic changes in the course of the development from chronic obstructive pulmonary disease to cor pulmonale]. AB - Swan-Ganz catheterization was done in 36 cases of COPD (19 cases) and chronic cor pulmonale (17 cases) patients diagnosed clinically. The results showed that exercise might greatly increase the rate of early diagnosis of chronic cor pulmonale in 47.4%, which is significant in clinical practice, together with gamma-camera, echocardiography and vectorcardiography, it can further increase the early diagnostic rate of cor pulmonale. In these 36 cases, 13 cases had no pulmonary hypertension and in 7 cases of them pulmonary arterial mean pressure were still in normal range even after exercise. If only right heart catheterization was used to diagnose cor-pulmonale without above three noninvasive examinations mentioned above, a high rate of misdiagnosis cor pulmonale would be possible. PMID- 1879026 TI - [Pulsed Doppler echocardiography assessment of acute hemodynamic effects of nifedipine on pulmonary hypertension in chronic obstructive lung disease]. AB - To observe acute hemodynamic effects of pulmonary hypertension in chronic obstructive lung disease by nifedipine, we studied 16 patients with pulsed doppler ultrasound. Pulsed doppler ultrasonogram was employed to measure hemodynamic parameters before and 45 minutes after nifedipine 20 mg (give po) in 16 patients. Results indicate that PAMP decreased significantly (P less than 0.01) from 5.5 +/- 1.6 to 4.0 +/- 1.5 kPa. We conclude that nifedipine reduces pulmonary artery pressure, at least acutely, in patients with hypoxic pulmonary hypertension. PMID- 1879027 TI - [Ultrasonically nebulized hypertonic saline as a provocation agent in asthmatics]. AB - We investigated nonspecific reactivity to inhaled aerosol of hypertonic saline. Hyperosmotic challenge carried out with NaCl solution of 0.9-fold increasing concentration from 2.7 to 7.2%. Each aerosol inhalation at different concentration was carried out for 5 min. An ultrasonic nebulizer was used to generate aerosol of NaCl solution that was delivered by tubing to a two-way valve. FEV1 was measured 1.0, 1.3 and 2 min after each concentration and did further at 5 min intervals until the value reached a plateau or began to rise. The challenge was terminated when the percentage fall in FEV1 was greater than 20%. The response to HS was expressed as PC20. In the 26 subjects with stable asthma 23 were responsive to HS. The PC20-HS was from 1.65 to 6.06%. The peak bronchoconstrictor effect of HS inhalation occurred 3 min after inhalation and its mean duration was 45 min. We also compared bronchial response to HS with that to methacholine (MCH). There was a significant correlation between PC20-HS and PC20-MCH (r = 0.538, P less than 0.01). The method used for HS challenge is simple, rapid, inexpensive and provide a new means for determination of bronchial hyperreactivity. PMID- 1879028 TI - [Primary research on the clinical significance of ventricular late potentials (VLPs), and the impact of mexiletine, lidocaine and Astragalus membranaceus on VLPs]. AB - The body surface signal-averaged electrocardiogram (SAECG) was recorded on 316 cardiac patients, 84% (266 patients) of whom were also taken 24-hour Holter ECG. VLPs were detected positively in 6.1%, 25%, 25.7%, 14.3% and 5.5% of patients with angina pectoris, myocardial infarction, myocarditis, cardiomyopathy and arrhythmia of unknown origin respectively, and the patients with complex ventricular arrhythmia had more VLPs positive determination definitely (P less than 0.05). The specificity of VLPs in the prediction of complex ventricular arrhythmia was greater than 80%, and the positive predictive accuracy was 70-80%. 5, 5 and 10 patients with VLPs were treated with Mexiletini Hydrochloridum, Lidocaini Hydrochloridum and Injection of Astragalus membranaceus respectively. As a result of treatment, the transfer of VLPs positive to negative was unsuccessful, but only the intervention of Astragalus membranaceus Injection made the duration of VLPs shortened significantly (39.8 +/- 3.3 ms versus 44.5 +/- 5.9 ms, P less than 0.01). PMID- 1879029 TI - [A preliminary study on hemodynamic changes of the heart-asthenia syndrome]. AB - In this paper, hemodynamic changes of 254 subjects were observed by using impedance cardiogram in a double-blind control method. The subjects were divided into 5 groups: heart-asthenia syndrome (98 cases), lung-asthenia syndrome (23 cases), spleen-asthenia syndrome (23 cases), kidney-asthenia syndrome (10 cases) and normal group (100 cases). The results showed that hemodynamic abnormalities occurred in the patients with heart-asthenia syndrome only, the changed regularities were that deficiency of both vital energy and Yin greater than deficiency of heart-Yang greater than deficiency of heart-energy greater than deficiency of heart-Yin. When stroke volume (SV), cardiac output (CO), cardiac index (CI), stroke volume index (SVI), heather index (HI), vascular compliance (C) and ejection fraction (EF) were decreased and total peripheral resistance (TPR) and systolic time interval (STI) were increased, the signs and heart asthenia syndrome could be found in clinical practice. In conclusion, the above parameters had certain diagnostic value for heart-asthenia syndrome and could be subjective quantitative indices for evaluating effects of treating the heart asthenia syndrome. PMID- 1879030 TI - [Clinical and experimental study of tablet cucumber vine compound in treating essential hypertension]. AB - 389 patients with essential hypertension were divided into two groups randomly. 241 patients were treated by tablet of cucumber vine compound and 148 patients by tablet of hypotension compound as control. The symptomatic marked improvement and total effective rate were 63.1% and 81.7% in the treated group and 39.2% and 67.0% (P less than 0.01) in the control group respectively. The marked effective rate in decrease of blood pressure and total effective rate were 52.7%, 90.9% and 58.1%, 92.6% (P greater than 0.05) respectively. Experiments with animals showed that tablet cucumber vine compound possessed persistently decreasing effect on the blood pressure and marked effect on increasing coronary blood flow and improving myocardial contraction. Clinical observation and toxicological test proved that tablet cucumber vine compound had no toxicity and had few side effects and that it was an effective, safe medicine for essential hypertension. PMID- 1879031 TI - [Long-term changes in the different types of coronary diseases treated with traditional Chinese and Western medicine]. AB - 64 cases with TCM differential types of CHD treated with TCM-WM in long term (an average of 10.5 years) were divided into four types according to deficiency of Yang [including weakness of Q1], deficiency of Yin, blood stasis and disorder of Qi and phlegm. Compared with pre-treatment 42 cases (65.62%) with TCM differential types showed improvement or no change in group I, II (clinical total effective rate 92.86%, the significantly effective rate 40.98%). While 22 cases (34.38%) with TCM differential type became aggravated or worse (clinical total effective rate 54.54%, the significantly effective rate 13.63%). The report indicated that the results in comparing group I, II with group III, IV were statistically significant; age (P less than 0.01), course of disease (P less than 0.01), impairment of myocardium (P less than 0.05), complication (P less than 0.05), ratio of deficiency of Yang (P less than 0.01), blood stasis (P less than 0.01) and high coagulation of blood (P less than 0.01). Therefore the author suggests that it is necessary to protect Yang-Qi and prevent and treat the complication of the CHD patients. PMID- 1879032 TI - [Effect of eleutherosides on ventricular late potential with coronary heart disease and myocarditis]. AB - The article studied the curative effect of eleutherosides in patients with coronary heart disease and myocarditis whose ventricular late potential (VLP) were positive by means of control study. All the 57 patients were randomly divided into two groups. The 31 patients were classified as therapeutic group including male 25 and female 6, the ages ranged from 18-65 years old (mean 51.8). The other 26 patients were defined as control group including male 21 and female 5, the ages ranged from 16-63 years old (mean 50.8). The therapeutic group was treated with injectio acanthopanacis senticosi 40 ml dissolved in 5% dextrose injection 300 ml by intravenous drop once daily. The control group was given insulin injection 12 u and potassium chloride injection 1 g dissolved in 10% dextrose injection 500 ml also by intravenous drop once daily. Both courses of treatment were 15 days. The rates of changing positive VLP into negative in two groups were 74.29% vs 34.6% (P less than 0.005). The results proved that eleutherosides is an effective drug to patients with positive VLP. PMID- 1879033 TI - [Experimental and clinical study of tong jing bao and Angelicae complex injection in treating fallopian tube obstruction]. AB - Twenty-two female rabbits with fallopian tube obstruction as the model, were made by 25% Phenol-Tragacanth Mucilage in the laboratory study. Eight rabbits were treated by taking Tong Jing Bao and giving transcervical intrauterine injecting of Angelicae complex injection. Seven were treated with the latter and other seven with 0.9% saline only as the control group. The study showed that in the opening fallopian tube, anti-inflammation, limiting the hyperplasia of fibro connective tissue and improving the regeneration of epithelial tissue, the first group was more effective than the other two groups (P less than 0.05). Forty eight infertile women, in whom the fallopian tube obstruction were proved by hysterosalpingography, were divided into two groups for the clinical study. Thirty patients were treated as same as the first group of rabbits. As the control group, other eighteen women were treated with transcervical intrauterine injecting of gentamycin and 0.9% saline in 3 to 6 months. The effective rates were 94.6% and 56.6% (P less than 0.01) and the subsequent pregnancy rates were 46.7% and 27.8% respectively in the different two groups. PMID- 1879034 TI - [Protective effect of sheng mai injection on myocardial injury induced by adriamycin in cultured myocardial cells]. AB - The effect of sheng mai injection (SMI) on adriamycin-induced cardiotoxicity in cultured myocardial cells was examined. Adriamycin treatment (1 mg/L) for 4 h of culture age, increased remarkably the leakage of lactate dehydrogenase (LDH) from the myocardial cells, and induced the damage of ultrastructure. SMI (30 mg/L, 100 mg/L, 300 mg/L) had no effects on these changes induced by adriamycin. The results showed that SMI had no direct protective effect on adriamycin cardiotoxicity in cultured myocardial cells. It's protective effect on adriamycin cardiotoxicity seems to be in whole body level, the mechanism of which was relating to the metabolism of the drug in organism, and is worthy of further research. PMID- 1879035 TI - [Effects of ursodeoxycholic acid on mechanical and electric activities in isolated guinea pig heart muscles]. AB - Using electromechanical transducer and conventional microelectrodes in isolated guinea pig heart muscles, the effects of ursodeoxycholic acid (UDCA) on the mechanical and electric activities were firstly observed. The results showed that, UDCA in dose of 0.05 mg/ml decreased contractile force by 36% (P less than 0.001) and shortened action potential duration (n = 3). It is inferred that UDCA may block inward calcium current. The results suggest that the action of UDCA is similar to that of bear bile and may be an effective composition of bear bile which acts on heart muscle. Our findings provide the experimental basis for the clinical application of UDCA. PMID- 1879036 TI - [Integration of macro and micro syndrome differentiation]. PMID- 1879037 TI - [Progress in pharmacological research on radix Astragali]. PMID- 1879038 TI - [Advance in drug treatment of primary and familial hypercholesterolemia]. PMID- 1879039 TI - Enzyme-linked immunosorbent assay of SIgA in whole saliva of healthy subjects and patients with oral diseases. AB - The author tried to determine the secretory immunoglobulin A (SIgA) level in the whole saliva of healthy subjects and patients with oral diseases by the enzyme linked immunosorbent assay (ELISA) technique. An ELISA system that was previously developed for determining the SIgA level in the pancreatic juice was modified and was proved to be applicable for the SIgA in the whole saliva. It was found that the SIgA in the whole saliva could be determined with excellent reproducibility and linearity when the samples were diluted 1,000-fold. This assay method was superior to the conventional techniques in terms of accuracy, covering a wide range SIgA levels in the saliva. In the 74 healthy subjects, the SIgA level in the whole saliva did not show any major age- or sex-related difference. However, patients with leukoplakia, lichen planus and carcinoma in the oral cavity showed higher levels of SIgA. The elevated levels of SIgA in the saliva of these patients suggested that some local changes in immunological competence might occur due to prolonged exposure to the antigen in the oral cavity. PMID- 1879040 TI - Antitumor activities and schedule dependence of orally administered MST-16, a novel derivative of bis(2,6-dioxopiperazine). AB - We studied bioavailability, treatment schedule dependence, and therapeutic efficacy of orally administered MST-16, a novel derivative of bis(2,6 dioxopiperazine), against murine tumors and human tumor xenografts. The rate of its intestinal absorption was about 50%, and it was immediately metabolized to its parent compound, ICRF-154. Therapeutic efficacy of MST-16 was heavily dependent on the treatment schedule: 9 daily oral administrations and treatment every 4 h on day 1 only were much more effective against s.c.-implanted L1210 leukemia than a single dose or five daily administrations giving the same total dose. Orally administered MST-16 showed potent life-prolonging effects (196%, 219% and 148%) in mice inoculated i.p. with P388, L1210 leukemia, and C-26 colon adenocarcinoma, respectively, but had no effect on B16 melanoma inoculated in the same way. MST-16 inhibited more than 80% growth of Lewis lung carcinoma, B16 melanoma, and C-38 colon adenocarcinoma implanted s.c., but had only a minor effect on M5076 fibrosarcoma. Lung metastasis of Lewis lung carcinoma was also effectively suppressed. Furthermore, MST-16 significantly inhibited growth of human colon, lung and breast cancers implanted s.c. in nude mice. We also made a kinetic analysis of the in vitro cell-killing effect by ICRF-154, the active form of MST-16 in vivo. It demonstrated a cell cycle phase-specific and time-dependent action, providing a reasonable explanation for the schedule-dependent therapeutic effect of MST-16. PMID- 1879041 TI - Increased cytotoxicity of low-dose, long-duration exposure to 5-fluorouracil of V 79 cells with hyperthermia. AB - We examined the cytotoxic effects of combined low dose and long exposure to 5 fluorouracil (5-FU) and hyperthermia on Chinese hamster V-79 cells with reference to timing and sequence of administration. The survival rate following hyperthermia at 42 degrees C for 2 h alone was 95.4%, and that after exposure to 1.0 micrograms/ml/5-FU alone for 48 hours, 94.2%. With respect to the combination of 5-FU and heat, the survival rate of cells exposed to hyperthermia at 42 degrees C for 2 h followed by 1.0 micrograms/ml 5-FU treatment for 48 h followed by hyperthermia led to a survival rate of 10%. Flow cytometric analysis of V-79 cells after exposure to 1.0 micrograms/ml 5-FU for 48 h revealed an accumulation of cells in the S-phase; the percentage of S-phase exponential growing cells was 65% and the plateau phase was 38%. The former were more sensitive to heat than the latter cells according to the MTT assay. V-79 cells pretreated with 5-FU were more sensitive to hyperthermia than were those not pretreated with 5-FU. Therefore, when 5-FU plus heat is to be used to treat a patient with a malignancy, the sequence of 5-FU followed by hyperthermia may be more effective than the reverse. PMID- 1879042 TI - Quercetin inhibits the growth of a multidrug-resistant estrogen-receptor-negative MCF-7 human breast-cancer cell line expressing type II estrogen-binding sites. AB - It has been demonstrated that the flavonoid quercetin (3,3',4',5,7 pentahydroxyflavone; Q) inhibits the growth of several cancer cell lines. There is evidence suggesting that the antiproliferative activity of this substance is mediated by the so-called type II estrogen-binding site (type II EBS). We looked for the presence of type II EBS and the effect of Q on the proliferation of an Adriamycin-resistant estrogen-receptor-negative human breast-cancer cell line (MCF-7 ADRr). By whole-cell assay using estradiol labelled with 6,7-tritium [( 3H]-E2) as a tracer, we demonstrated that MCF-7 ADRr cells contain type II EBSs. Competition analysis revealed that diethylstilbestrol (DES) and Q competed with similar potency for [3H]-Es binding to type II EBSs. The antiestrogen tamoxifen (TAM) competed for type II EBSs, albeit to a lesser extent than either DES or Q. Growth experiments demonstrated that Q and DES exerted a dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM, whereas TAM was less effective. Q could also inhibit colony formation in a clonogenic assay. Our results indicate that multidrug-resistant estrogen receptor-negative MCF-7 cells express type II EBSs and are sensitive to the inhibitory effect of Q. This substance could be the parent compound of a novel class of anticancer agents. PMID- 1879043 TI - Effects of pirarubicin, an antitumor antibiotic, on the cardiovascular system. AB - In the present study we examined the effects of pirarubicin [(2"R)-4'-O tetrahydropyranyladriamycin, THP] on a cardiovascular system. An injection of THP (0.39-3.13 mg/kg, i.v.) reduced the mean blood pressure and caused an increase in the respiratory air rate in anesthetized rats. At 1.5 x 10(-6)-1.5 x 10(-5) M, THP markedly relaxed a contraction induced by 10(-7) M norepinephrine in rat aorta with endothelium but not in that without endothelium. At a dose of 0.02-0.5 mg, THP produced an increase in the contractile force and the perfusion flow of isolated perfused guinea pig hearts. At a higher concentration (4.5 x 10(-5)-1.5 x 10(-4) M), it produced a slight increase in the contractile force of the left atria in guinea pigs. This positive inotropic action of THP was inhibited by diphenhydramine (10(-6)-5 x 10(-5) M), chlorpheniramine (3 x 10(-7)-3 x 10(-5) M), and tripelennamine (3 x 10(-7)-3 x 10(-5) M) but not by propranolol (10(-6) M), cimetidine (10(-5) M), diltiazem (10(-6) M), or ryanodine (10(-8) M). THP given i.v. at 2.5 mg/kg elevated the plasma histamine level in anesthetized dogs. From these data, we conclude that THP mainly relaxed the rat aorta in the presence of endothelium and that at higher concentrations, it increased the contractile force in the cardiac muscle, probably mediated through the release of histamine. PMID- 1879044 TI - Differential properties of cisplatin and tetraplatin with respect to cytotoxicity and perturbation of cellular glutathione levels. AB - We compared the cytotoxicity and the effects on the levels of cellular glutathione (GSH) of cisplatin and tetraplatin in the mouse mammary tumour cell line EMT6/P and a cisplatin-resistant variant. EMT6/CPR. EMT6/CPR showed a 2.5 fold resistance to cisplatin but no cross-resistance to tetraplatin. Basal cellular GSH levels in the resistant line were 1.7-fold those in the parent cell line. On exposure of cells to cisplatin, cellular GSH levels initially dropped in both cell lines but subsequently rose. At between 1 and 4 h after the onset of drug exposure, GSH levels were up to 2-fold the baseline levels. The cisplatin resistant subline displayed higher GSH levels than the parent cell line at all time points. Tetraplatin failed to influence cellular GSH levels in either of the cell lines. PMID- 1879045 TI - The effects of cisplatin on the concentration of protein thiols and glutathione in the rat kidney. AB - The effect of a nephrotoxic dose of cisplatin (5 mg/kg) on the concentrations in the rat kidney of both glutathione and protein-bound thiols was investigated. Total glutathione and oxidised glutathione were measured in the cortex and outer medulla using specific enzyme-based assays. The high-molecular-weight thiols were quantified in cells of the proximal tubule using a cyto-chemical technique. The concentration of total glutathione (oxidised and reduced) in the kidney cortex and outer medulla was significantly higher than that of controls at 1 h following cisplatin administration. The amount by which the concentration in treated animals exceeded that in controls increased to 50% at 72 h and remained significantly elevated for 120 h following treatment. This increase was mainly attributable to an increase in the concentration of reduced glutathione. In contrast, the concentration of protein thiols in the proximal tubules decreased significantly at 8 h after dosing, reaching a nadir 29% below that of controls at 120 h, thus coinciding with the maximal functional disturbance in the kidney as reflected by the concentration of blood urea. The decrease in protein thiols could not be correlated stoichiometrically with the platinum concentration in the cortex and outer medulla, which reached a peak of 16.3 +/- 0.3 micrograms/g wet tissue at 72 h after treatment. Evidently cisplatin perturbs the equilibrium that is said to exist between the concentration of reduced glutathione and that of protein thiols. This perturbation occurs well before the onset of overt functional disturbance of the kidney and is evident before the point at which the damage to the kidney caused by cisplatin becomes irreversible. PMID- 1879046 TI - Pharmacokinetics of fotemustine and BCNU in plasma, liver and tumor tissue of rats bearing two lines of Walker 256 carcinoma. AB - The plasma and tissue pharmacokinetics of fotemustine (diethyl-1-[3-(2 chlorethyl)-3-nitrosoureido]-ethylphosphonate+ ++) and BCNU (1,3-bis-[2 chlorethyl]-1-nitrosourea) were investigated in healthy control rats and in animals bearing either the nitrosourea-sensitive line A (W256/A) or the nitrosourea-resistant line B (W256/B) of Walker 256 carcinoma. The antitumor activities of these nitrosoureas were similar following i.v. doses ranging from 10 to 40 mg/kg. For both drugs, the survival of tumor-bearing rats was lower in the W256/B than in the sensitive W256/A line. Some sex differences were observed, female rats being more responsive than males to both drugs. Nitrosourea concentrations were assayed in plasma and tissues by differential pulse polarography so as to assess whether the pharmacokinetics could explain the differences in antitumor activity. The antineoplastic effects of fotemustine seemed to be influenced by its pharmacokinetics. The plasma AUC of the intact nitrosourea was higher in females than in males. Fotemustine was cleared 2-5 times more slowly than BCNU from tumor tissue, and its clearance was higher in W256/B- than in W256/A-bearing rats. This suggests that the antitumor activity in the responsive line might partly be due to longer exposure of the growing tumor to the drug. The distribution volume of both nitrosoureas in plasma was higher in tumor-bearing animals than in healthy controls, indicating that the tumor tissue probably constitutes an additional distribution space. PMID- 1879047 TI - Comparative pharmacokinetics of doxorubicin given by three different schedules with equal dose intensity in patients with breast cancer. AB - The pharmacokinetics of doxorubicin given according to three different schedules with a similar dose-time intensity have been studied and compared in 16 women with metastatic breast cancer. Six patients were treated with doxorubicin 75 mg/m2 by i.v. bolus repeated every 3 weeks; 5 patients received doxorubicin by 4 day continuous infusion every 3 weeks (4 at 75 mg/m2 and 1 at 60 mg/m2); 5 patients received 25 mg/m2 by i.v. bolus given weekly. Timed blood samples were collected and plasma levels of doxorubicin and its metabolite doxorubicinol were measured by high-performance liquid chromatography with fluorescence detection. Peak plasma concentrations were measured, and areas under the concentration-time curves calculated. Peak plasma levels of doxorubicin were significantly lower with the 4-day infusion than with either of the bolus injections. The 4-day infusion, however, gave significantly greater total exposure to doxorubicin and doxorubicinol, as indicated by area under the concentration-time curve, than weekly or 3-weekly bolus treatment. A single bolus injection of doxorubicin 25 mg/m2 yielded a total exposure to doxorubicin approximately half that achieved with a 75 mg/m2 bolus injection. Over a 3-week period, therefore, total exposure to doxorubicin would be greater with the weekly low-dose schedule than with the 3 weekly administration. We conclude that drug scheduling has significant effects on doxorubicin pharmacokinetics. PMID- 1879048 TI - Experimental basis for increasing the therapeutic index of carboplatin in brain tumor therapy by pretreatment with WR compounds. AB - We tested an experimental strategy to decrease the dose-limiting hematotoxicity of carboplatin without compromising its activity against brain tumors. The effect of pretreatment with WR-1065, a chemomodifier that penetrates brain poorly, on carboplatin's cytotoxicity was evaluated in human hematopoietic granulocyte monocyte progenitor cells and in three human glioblastoma cell lines. WR-1065 reduced bone marrow toxicity without decreasing carboplatin's activity against glioblastoma cells. These results suggest that the therapeutic index of carboplatin might be increased in the treatment of malignant brain tumors. PMID- 1879049 TI - The use of nasal calcitonin spray in the treatment of hypercalcaemia of malignancy. PMID- 1879050 TI - Comparative intraperitoneal pharmacokinetics of three platinum analogues. AB - The pharmakokinetic profiles of intraperitoneally infused platinum analogues were determined in 13 women exhibiting minimal residual disease following surgery and systemic chemotherapy for epithelial ovarian cancer or fallopian tube carcinoma by following the disposition of tracer doses of 195mPt radiolabel. Six patients received iproplatin, four were given cisplatin and three received carboplatin. The present data demonstrate no difference in the disposition of total platinum between these three analogues, but differences in the kinetics of free platinum may exist. PMID- 1879051 TI - EEG in early HIV-1 infection is characterized by anterior dysrhythmicity of low maximal amplitude. AB - We analyzed the EEGs of 67 HIV-1-infected patients at various stages of the disease and of 35 HIV-1-seronegative controls. The most common EEG abnormality in HIV-1 infection was an increased amount of generalized episodic or persistent, predominantly anterior slow activity, associated with a low level of maximal amplitude. When compared to the controls, a lower maximal amplitude of dominant background activity (p less than 0.001), and more marked generalized (p less than 0.01) and anterior (p less than 0.001) disturbances were already seen in early stages of HIV-1 infection. EEG abnormalities were more severe in patients with advanced HIV-1 infection than in those at early infection (p less than 0.001 to p less than 0.05). The presence of a more marked, posteriorly (p less than 0.01) accentuated, generalized slow activity (p = 0.02) was found more often in patients with T-helper cell counts lower than 0.4 x 10(9) (p = 0.05) than in those with higher numbers of T-helper cells. No clear associations were found between the severity of EEG abnormalities and the duration of HIV-1 infection. Our results suggest that EEG is a sensitive method in detecting subclinical functional cerebral disturbances caused by HIV-1. PMID- 1879052 TI - Recovery of cognition from persistent vegetative state in a child with normal somatosensory evoked potentials. AB - The absence of bilateral early cortical SEPs in a PVS due to nontraumatic coma is usually associated with failure to recover cognition or awareness, although rarely patients with bilaterally absent cortical SEPs in posttraumatic PVS may regain cognition. On the other hand, normal cortical SEPs in nontraumatic coma may be related to favorable outcomes as shown in this patient and other reports. Our patient is unique in that he had had serial normal SEPs, was in a PVS for 7 1/2 months, and recovered cognition, but not without cost in terms of damage to intellectual capability. Further long-term clinical follow-up studies to correlate clinical outcome with serial SEP data may be indicated. PMID- 1879053 TI - Sleep spindles in epilepsy. AB - Spindles are a ubiquitous phenomenon in sleep, but their physiology and the effects of neurologic disorder on their frequency and amplitude are incompletely understood. We compared the incidence of three commonly defined spindle types (14 15 Hz, 12-13 Hz, and 10 Hz) and the frequency and amplitude of spindles during Stage II sleep in 50 patients with complex partial, partial and secondarily generalized, and primary generalized seizures, with and without interictal behavioral symptoms. All patients had 12-13 Hz and 14-15 Hz spindles of symmetric character in C3-A1 and C4-A2 derivations during prolonged sleep-deprived EEG recordings, which were normal except for partial or generalized epileptiform activity. Seventy-one per cent of complex partial seizure patients had 10 Hz spindles, and they occurred in 50% of the other two groups, predominating among those with interictal behavioral symptoms in all groups. Spindle frequency was significantly less in patients with generalized epilepsy than with partial seizures, and patients with complex partial seizures and partial seizures with secondary generalization differed significantly in spindle frequency. Spindle frequency was significantly lower with polypharmacy than with monotherapy. Patients whose regimens included phenobarbital had significantly lower spindle frequencies and spindle frequencies differed significantly between phenytoin and carbamazepine. Differences in spindle frequency may be due to residual medication effects, underlying encephalopathy or physiological differences between partial and generalized epilepsy. PMID- 1879054 TI - The effect of spikes and spike-free epochs on topographic brain maps. AB - Maps of foci, when no discharges nor obvious slow activity were included in the map, usually (84%) showed changes within the focus itself and also in adjacent areas (58%) and often (47%) in the mirror region. An increase in activity was more often seen in the more active foci, especially in the delta and beta 2 ranges, and decrease in activity was usually seen with inactive foci. When discharges were included in the maps, an increasing number was associated with an increase at the main focus in all ranges, especially in delta and beta 1, but much less often in beta 2. The amount of electrical charge required for a change in the map with spikes was approximately 40 nanocoulombs (nC) for the first and second changes, increasing to around 50 nC with adjacent or separate foci. "Artificial" spikes produce more delta activity than other frequency ranges and the FFT of various pulses show maximal amplitudes at the slowest frequencies. PMID- 1879055 TI - Considerations of secondary temporalization. AB - In generalized forms of epileptic seizure disorder, secondary focal involvement of the temporal lobe may gradually develop. Such signs of "secondary temporalization" may manifest themselves in the seizures type (occurrence of complex partial seizures) and in the EEG. Fourteen observations of secondary temporalization are reported: 3 of them in cases of primary generalized epilepsy and 11 in patients with Lennox-Gastaut syndrome. In 9 patients, additional depth implants were carried out in order to detect a primary focal epileptogenic lesion. Secondary temporalization is likely to be caused by independent paroxysmal activity evolving in the limbic structures (amygdala, hippocampus) due to their role of "low threshold areas." Postconvulsive hypoxic damage of the hippocampus is possible but a much less likely cause of secondary temporal lobe manifestations. PMID- 1879056 TI - Quantitative measurement of delta activity in Alzheimer's disease. AB - Quantitative measurements of delta activity were made in 10 healthy elderly controls and 31 subjects with Alzheimer's disease. Delta activity did not discriminate between the healthy elderly controls and the early mild Alzheimer's disease subjects. However, delta activity was a significantly greater percentage of total EEG power in the moderate-to-advanced Alzheimer's subjects when compared to either the healthy controls or mild Alzheimer subjects. In the T3 and T4 electrodes, delta activity in the moderate-to-advanced Alzheimer subjects was 78.3% and 47.6% higher, respectively, than in control subjects. Furthermore, delta activity was an excellent predictor of dementia severity within the 31 subjects with Alzheimer's disease. PMID- 1879057 TI - Tooth pulp evoked potentials (TPEPs) in multiple sclerosis patients. AB - The purpose of this study was to determine possible changes of the tooth pulp evoked potentials in patients with multiple sclerosis, and to compare these with other types of evoked potentials, in the same patients. The results showed TPEP changes in all multiple sclerosis patients. In 12 patients the changes were observed on both sides, while in 6 on one side only. It is interesting to note that the second negative wave was characterized by two peaks. The first peak possessed latency of approximately 125 ms that was significantly shorter than in the control group. The second peak appeared after about 195 ms. The significant prolonged latency of the second negative wave was observed in 100% of TPEPs, 95% VEPs and 72% AEPs. In only one case the changes were observed in TPEPs, while VEPs and AEPs were normal. It could be concluded that TPEPs, as well as other types of evoked potentials, are a sensitive indicator of the demyelination process. PMID- 1879058 TI - Auditory evoked potentials in borderline personality disorder. AB - Borderline personality disorder is an increasingly recognized condition and frequent management problem in psychiatric and nonpsychiatric practice. Paroxysmal changes in affect and behavior, high incidence of soft neurologic signs and frequent EEG alterations, and evidence of clinical response to antiepileptic drugs have suggested cerebral dysfunction, particularly involving the limbic system or reticular activating system. We recorded early latency brainstem auditory evoked potentials (BAEPs) and long-latency auditory event related potentials (ERPs) in 20 patients fulfilling DSM-III-R criteria for this disorder. BAEPs were recorded from Cz to ipsilateral and contralateral ear reference, with rarefaction clicks presented at 11.1 per second and 70 dB SL. Two thousand averages were recorded and replicated for each ear, with filter band pass of 150-3000 Hz and 10 ms analysis time. ERPs utilized binaural stimulation with 1000 and 3000 Hz tones in an 80:20 ratio, with interstimulus interval 1.1 second, analysis time 1000 ms, and filter band pass 1-100 Hz. Two hundred averages were recorded and replicated from Cz with linked ear reference. No differences were evident in I-III, III-V, and I-V interpeak latencies between borderline patients and age-matched neurologically and audiologically normal controls. N1, P2, and N2 components of the AEPs were longer in latency and lower in amplitude in borderline patients, while P3 latency was longer and amplitude was attenuated in borderline patients as compared to controls. These findings may suggest differences from normals in attention maintenance and in limbic system function. PMID- 1879059 TI - Growth characteristics and response to growth hormone therapy in patients with hypochondroplasia: genetic linkage of the insulin-like growth factor I gene at chromosome 12q23 to the disease in a subgroup of these patients. AB - Hypochondroplasia, a heterogeneous and usually mild form of chondrodystrophy, is a common cause of short stature. It often goes unrecognized in childhood and is diagnosed in adult life when disproportionate short stature becomes obvious. We performed restriction enzyme analysis of the insulin-like growth factor I (IGF-I) gene on the families of 20 white British Caucasian children with short stature attributed to hypochondroplasia by radiological and clinical criteria, who were undergoing human growth hormone (r-hGH) treatment, in 60 children with isolated growth hormone deficiency and in 50 normal individuals. The frequency of the heterozygous pattern (Hind III: 8.2, 5.2, 4.8, 3.2 kb fragments, Pvu: 8.4, 5.1, 4.7, 2.5 kb fragments) in children with hypochondroplasia was significantly higher (chi2: P less than 0.05) than in the control groups. The hypochondroplastic children whose response to r-hGH treatment was characterized by a proportionate increase in both spinal and subischial leg length were all heterozygous for two co-inherited IGF-I gene restriction fragment length polymorphism (RFLP) alleles (Hind III: 5.2, 4.8 kb; Pvu II: 5.1, 4.7 kb). Children whose response was characterized by accentuation of the body disproportion by r-hGH treatment were all homozygous for these alleles (Hind III: 4.8, 4.8 kb; Pvu II: 4.7, 4.7 kb). Their response to r-hGH treatment is significantly different (P less than 0.01). Studies of the families of the heterozygous affected children demonstrated strong linkage (lod score 3.311 at zero recombination) of the IGF-I gene locus at chromosome 12q23 to this subgroup of hypochondroplasia. The 5.2 kb Hind III and 5.1 kb Pvu II alleles are in strong linkage disequilibrium with this trait. These data indicate that IGF-I gene may be a candidate gene for involvement in the aetiology of short stature presenting with hypochondroplastic features and a proportionate response to r-hGH treatment; they also provide support for the concept of genetic heterogeneity in chondrodystrophy. PMID- 1879060 TI - d-fenfluramine/prolactin response throughout the menstrual cycle: evidence for an oestrogen-induced alteration. AB - The prolactin (PRL) response to fenfluramine (FEN), a serotonin (5-HT) releasing agent, is used as an index of 5-HT sensitivity in studying disorders associated with central 5-HT abnormality. Plasma oestrogen levels are known to augment PRL responses to a variety of stimuli. In order to examine the effect that ovarian steroids have on this response nine, healthy women were tested twice at three time points in the menstrual cycle: early follicular, mid-cycle and late luteal phase with either d-FEN, a more specific 5-HT agent than the racemic mixture, or placebo. Responses to d-FEN were maximal at mid-cycle, lowest during the early follicular phase, with responses premenstrually being intermediate between the two. Responses to placebo did not vary. Plasma oestradiol levels fluctuated in parallel with neuroendocrine responses to d-FEN. The possible mechanisms are discussed, including an effect that oestradiol may exert at central serotonin sites. PMID- 1879061 TI - Glucose metabolism in patients with Cushing's syndrome. AB - Glucose intolerance, sometimes severe enough to cause frank diabetes mellitus, is a frequent feature of Cushing's syndrome. The primary cause of the hyperglycaemia, whether due to glucose over-production or under-utilization, remains unresolved. We therefore measured glucose turnover using an intravenous bolus of 3-3H glucose in 14 normoglycaemic patients with Cushing's syndrome and 14 control subjects. Seven of the patients with Cushing's syndrome were also restudied post-operatively. Plasma glucose concentrations were similar in all three groups whereas glucose metabolic clearance rate (MCR) (1.80 +/- 0.06 ml/min/kg) and glucose turnover rate (9.09 +/- 0.36 mumol/min/kg) were significantly reduced in patients with Cushing's syndrome compared to normal subjects (2.21 +/- 0.1; P less than 0.001; 10.90 +/- 0.50; P less than 0.01) and rose post-operatively to normal values (2.35 +/- 0.14 ml/min/kg; 11.07 +/- 0.48 mumol/min/kg). We conclude from these results that the hyperglycaemia sometimes found in Cushing's syndrome may be primarily due to decreased utilization rather than increased glucose production. PMID- 1879062 TI - The diagnosis and differential diagnosis of Cushing's syndrome. PMID- 1879063 TI - The value of medical treatment in nasal polyps. PMID- 1879064 TI - Blood transfusion and laryngeal cancer. AB - Evidence exists to suggest a detrimental effect of blood transfusion on survival after resection for malignant disease. Immune suppression due to transfusion has been implicated, though this remains unproven. We have conducted a retrospective study of 69 patients (38 transfused, 31 not transfused) with squamous carcinoma of the larynx to assess the effect of blood transfusion on survival after laryngectomy. Patients were compared for age, sex, smoking habit, tumour site and stage, grade of operating surgeon, preoperative haemoglobin, tumour nucleolar organizer region status, and operation time. The minimum follow-up was 5 years. In the transfused group 21/38 died as a result of their malignant disease and only 4/31 in the untransfused group. This difference was highly significant (P less than 0.001, chi-squared test) and using a multivariate analysis the only variable associated with a decreased survival time was whether a blood transfusion had been received. We conclude that peri-operative blood transfusion is associated with decreased survival after laryngectomy. However, whether this association is causal remains unproven. PMID- 1879065 TI - The management of peritonsillar sepsis by needle aspiration. AB - 172 consecutive patients admitted with suspected unilateral peritonsillar sepsis were studied. Needle aspiration of the peritonsillar space was performed, and they were all then treated with intravenous antibiotics (usually benzylpenicillin). Any pus obtained was cultured. The aspiration was repeated if the patient was not improving after 24 h. A quantity of pus was aspirated at the first attempt from 91 patients (53%); 82 of these required no further aspiration but 7 required a further single aspiration and 2 required a further 2 aspirations before resolution of the sepsis. 71 of the 81 patients (88%) from whom pus had not been aspirated, and who were therefore initially considered to have peritonsillar cellulitis, required no further aspirations. However, 6 subsequently drained pus spontaneously and 4 produced a positive aspirate on a second occasion. Four patients required a change in their antibiotic therapy. We have found the combination of needle aspiration and parenteral antibiotics to be an effective treatment of peritonsillar sepsis. All patients were spared the unpleasant and painful experience of an incision and drainage procedure. PMID- 1879066 TI - Cough intensity in patients with a vocal cord palsy. AB - This study assesses the effect a paralysed cord has on the intensity of coughing. The air flow pattern during coughing of 10 patients with a vocal cord palsy was compared with a control group, using a computerized pneumotachograph system. There was no significant difference in the value of the peak air flow but the time taken to reach the maximum value was prolonged in the vocal cord palsy group. This non-invasive test may aid diagnosis of vocal cord palsies but the laterality of the lesion cannot be predicted from the airflow pattern alone. PMID- 1879067 TI - Surgery for chronic ear disease in a non-university hospital: open cavity, obliteration and intact canal wall techniques. AB - The long-term results of surgery for chronic suppurative middle ear disease at a non-university ENT-clinic (Vasa Central Hospital, Finland) are reported. The material consisted of 273 ears, 65 of which had been operated on by open cavity techniques, 178 by the original Palva obliteration method, and 30 by the intact canal wall method. Post-operative cholesteatoma occurred equally frequently with the two canal wall down methods (7.7 and 7.3%, respectively) but was more frequent after intact canal wall surgery (23.3%). Hearing was better and the infection rate lower with obliteration than with open cavity techniques. Post operative infection was the least frequent and the hearing result best in the intact canal wall ears, but compared to the other two groups the extent of disease found at surgery was considerably less in this group. The obliteration operation proved to be a safe method in the hands of a practising otologist outside university clinics. PMID- 1879068 TI - Is laterality important in neck node metastases in head and neck cancer? AB - We present a series of 2219 previously untreated squamous carcinomas of the head and neck, 141 (6.5%) of whom had bilateral nodes at presentation. Bilateral nodes became progressively less common with increasing age but were not related to other host factors. They were also strongly related to the site of the primary tumour, its T-stage and its histological grade, being more common in tumours of the oro or naso-pharynx, in poorly or moderately differentiated tumours, and in tumour stages T3 or T4 at presentation. There were also interactions between these tumour factors, and patients with all three factors had a 25% incidence of bilateral nodes. 126 of these patients could be matched for the main prognostic factors with 126 patients with unilateral neck node disease. The survival rate of the latter group was 9% better than that of the unilateral group. Further breakdown showed that the survival of patients with nodes smaller than 6 cm is not affected by laterality, whereas it is for patients with massive nodes. PMID- 1879069 TI - Secretory otitis media: a review of management by consultant otolaryngologists. AB - A questionnaire concerning various aspects of secretory otitis media was completed by a random sample of Consultant Otolaryngologists in the United Kingdom. The replies to questions associated with the management of this condition are presented. The results suggest only a moderate degree of agreement between Consultants in many areas of management and these findings are discussed in the light of current research. PMID- 1879070 TI - Is a single quinsy an indication for tonsillectomy? AB - There has recently been some discussion on whether a single quinsy is an indication for tonsillectomy. This paper presents a retrospective study of 36 patients who presented with a quinsy over the past 37 years but did not have interval tonsillectomy. Prolonged follow-up shows that the rate of recurrence of a quinsy can double compared to the recurrence rate under 5 years. Despite this it remains relatively low and an uncomplicated quinsy does not warrant tonsillectomy. PMID- 1879071 TI - The protective effect of a conductive hearing loss in workers exposed to industrial noise. AB - There is controversy as to whether a conductive hearing loss protects the inner ear from the effects of loud noise. A retrospective study was carried out on 24 patients with a combination of unilateral conductive hearing loss and noise induced hearing loss. This allowed subjects to act as their own controls. There was no statistical difference in thresholds between the two ears; possible explanations for this finding are discussed. PMID- 1879072 TI - The role of bupivacaine in post-tonsillectomy pain. AB - The peritonsillar tissues on one side of 45 consecutive patients undergoing tonsillectomy were infiltrated with bupivacaine and adrenaline, the opposite side serving as a control. Although a significant difference was noted between the two sides this was not a substantial difference in terms of pain relief. PMID- 1879073 TI - An analysis of the aetiology of early childhood deafness. AB - It is generally believed that one in every thousand children is profoundly deaf. An understanding of the aetiology of early childhood deafness and timely detection is crucial in rehabilitation of these children. This study analyses the aetiology of early childhood deafness and shows that deafness is more often acquired than inherited. Non-syndromic deafness, especially occurring on its own, usually produces profoundly deaf children and thus there is the need for genetic studies--in the child, laterally, and longitudinally into generations. Meningitis appears to be the commonest cause of acquired deafness, especially if due to pneumococcus. Only 40 of the 80 cases presented before the age of 2 years. It was therefore interesting to note what factors invoked awareness of deafness to facilitate early presentation. PMID- 1879074 TI - Ultrasonography as a method of examination of the frontal sinus. AB - This prospective study was performed to evaluate the reliability of ultrasonography for the detection of fluid and mucosal swelling in the frontal sinus. The evaluation was based on a comparison of the preoperative ultrasonographic results with the surgical findings in 27 frontal sinuses. Ultrasonography was found to be a reliable method for the demonstration or exclusion of mucosal swelling and accumulated fluid (sensitivity 92%; specificity 93%). PMID- 1879075 TI - Clinical investigation of hearing loss in the elderly. AB - The prevalence of hearing loss increases with age. Epidemiological and histopathological studies relating hearing loss to age are reviewed and clinical evidence presented suggesting that hearing loss is due not only to age but also to disease processes known to be associated with hearing threshold deterioration. 80 elderly patients presenting with a hearing problem at hospital have been studied and compared with 287 'non-complainers'. 83% of the study group were found to have factors, additional to age, contributing to their hearing loss; 50% had a medical condition previously unrecognized; 30% were taking potentially ototoxic drugs. Audiometric measurements indicate that hearing thresholds of the elderly are influenced by numerous disease processes. Patients attending hospital with hearing impairment are at greater risk of having a vascular or biochemical abnormality than a group of elderly 'non-complainers'. Elderly patients presenting with hearing loss should therefore be adequately investigated before being labelled as having presbyacusis. PMID- 1879076 TI - Function and morphology of respiratory cilia in situs inversus. AB - The activity and ultrastructure of respiratory cilia were studied in 13 individuals with situs inversus but without serious respiratory complaints, in 8 patients with Kartagener's syndrome and in 50 healthy controls without situs inversus. In 3 individuals with situs inversus abnormal ciliary activity was found, comparable in every aspect to the ciliary activity in patients with Kartagener's syndrome. In 4 individuals with situs inversus a dynein arm deficiency was present in the cilia, with abnormal ciliary activity in 3 of them. The number of outer dynein arms per cilium differed significantly between the 3 groups (P less than 0.02). Apparently, situs inversus without serious respiratory complaints can be associated with primary ciliary dyskinesia. Based on the findings in this study, the incidence of primary ciliary dyskinesia in the Caucasian population appears to be 1:12,500. PMID- 1879077 TI - The effect of frequency on combined glottography. AB - This study investigates the relationship between frequency and the open quotient (OQ) and speed quotient (SQ) values of combined glottography. Simultaneous electroglottography and photoglottography were performed on 20 healthy male subjects. Regression analysis showed that neither OQ nor SQ was dependent upon frequency. The technique is therefore still valid despite the inability to control this variable. PMID- 1879078 TI - The spontaneous course of nasal obstruction in patients with normal nasal airway resistance. AB - Sixty-seven patients, candidates for septoplasty in the years 1976-1978 because of nasal obstruction and deviated nasal septum, but not having surgery because their nasal airway resistance was normal, were reviewed in 1982 and again in 1989. Between 1982 and 1989, 6% of the patients became free of their respective nasal complaints, and 18% of their nasal obstruction, the corresponding overall figures for the period between 1976 and 1978, and 1989, being 20 and 36%. In fact, the majority of the patients were suffering from vasomotor rhinitis and because in so many cases nasal obstruction tends to disappear as time goes on, a conservative waiting policy would seem to be an appropriate approach to treatment. PMID- 1879079 TI - Surgical anatomy of the singular nerve. AB - The course of the posterior ampullary (singular) nerve has been studied in 30 preserved human temporal bones. In 17 dissections (57%), the nerve was readily accessible in the floor of the round window niche without undue risk to the round window membrane or the ampulla of the posterior semicircular canal. In 5 bones (16%), the nerve was closely related to the round window membrane and could not have been approached without significant risk of damage to the membrane. In 8 (27%), the nerve ran more or less directly medially to the internal auditory meatus without entering the round window niche. The ampulla of the posterior semicircular canal would therefore have been at risk if the nerve were approached surgically. PMID- 1879080 TI - Inverted papilloma of the nose and paranasal sinuses: a study of 67 patients. AB - Retrospectively, 67 patients with inverted nasal papillomas were studied. In 12, the lesions were localized exclusively on the nasal septum. In 55, the lesion involved the lateral wall and/or the paranasal sinuses. There was a male predominance of 3:1. After histological revision the most dominating epithelial type was found to be transitional. Inverted papilloma was in one patient associated with squamous cell carcinoma. Ten per cent suffered recurrences from 6 to 37 months after the primary surgical procedure. We found that limited septal lesions could be managed by an intranasal procedure but lateral rhinotomy is recommended as the procedure of choice in the treatment of inverted papilloma of the lateral wall. PMID- 1879081 TI - The P. Rambotti Lecture. Biology of autoimmunity: a review. PMID- 1879082 TI - A study of synovial membrane of patients with systemic lupus erythematosus (SLE). AB - In this study, 30 percutaneous synovial knee biopsies were taken from patients with systemic lupus erythematosus (SLE) that had been diagnosed in accordance with ARA criteria. Acute articular involvement was present in 16 cases. The synovial membrane was then examined using routine histological techniques and by direct immunofluorescent methods. The most frequently observed histological picture was comprised of: a) synoviocyte hyperplasia, b) scarce inflammatory infiltrate, c) vascular proliferation, d) oedema and congestion, e) fibrinoid necrosis and intimal fibrous hyperplasia of blood vessels, g) presence of fibrin on the synovial surface and fibrin-like deposits in the chorion. It is concluded that immunofluorescence can be used in the characterization of typical cases but is not specific. PMID- 1879083 TI - The role of interleukin 1, erythropoietin and red cell bound immunoglobulins in the anaemia of rheumatoid arthritis. AB - Since interleukin 1 (IL-1) and erythropoietin (Epo) are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) anaemia we measured IL-1 alpha and Epo concentrations in 10 RA patients with chronic disease anaemia (CDA) and in 14 RA patients without anaemia. Anaemic RA patients had significantly higher IL-1 alpha concentrations than patients without anaemia. IL-1 alpha correlated negatively with haemoglobin and correlated positively with ESR. The results of a multivariate analysis showed that the best predictors of the presence and absence of anaemia were IL-1 alpha and ESR. No clinical parameters permitted a distinction between these two groups of patients. Epo levels were not different in anaemic and non-anaemic RA patients. No correlation was found between Hb and Epo, indicating the presence of an impaired Epo response in RA patients with CDA. We completed our study with the determination of the mean red cell lifespan and with the quantification of IgG and IgM bound to the surfaces of red blood cells (RBC-IgG and RBC-IgM) using a sensitive ELISA method. We observed a modest reduction in red cell survival in anaemic RA patients compared to normal controls. We did not find any correlation between Hb and red cell lifespan and between Hb and RBC-IgG. RBC-IgG and RBC-IgM were not found to be more elevated in anaemic RA than in non-anaemic patients. PMID- 1879084 TI - Calcium influx into red blood cells: the effect of sera from patients with systemic sclerosis. AB - The rheology of red blood cells in patients with systemic sclerosis is abnormal. To investigate this further we have examined the effect of sera from patients with systemic sclerosis on the handling of calcium ions by the erythrocyte membrane. Normal erythrocytes were filled with a photoprotein (aequorin) which emits light on contact with calcium. These photoprotein loaded normal erythrocytes were then incubated overnight with serum from: normal subjects (n = 20), from patients with systemic sclerosis (n = 27) or from patients with primary Raynaud's disease (n = 10). There was no significant difference in basal calcium leakage, as measured by the amount of light produced following the addition of triton X-100. Induced calcium influx, as measured by the amount of light produced following the addition of ionophore A23817, was significantly greater in the photoprotein loaded erythrocytes incubated overnight with serum from patients with systemic sclerosis compared to those incubated with serum from normal subjects (p less than 0.02) or patients with primary Raynaud's disease (p less than 0.01). This modulation of Ca2+ handling in erythrocytes by a serum factor from patients with systemic sclerosis could account for the alterations in erythrocyte function, such as red cell deformability, observed in systemic sclerosis. PMID- 1879085 TI - Male lupus: prevalence of IgA deficiency, 7S IgM and abnormalities of reticuloendothelial system Fc-receptor function. AB - Serological studies conducted on sera from a group of 31 male SLE patients revealed a 32% prevalence of 7S IgM and a 9.7% prevalence of IgA deficiency. Previous reports using similar methods indicated a higher (43-50%) prevalence of 7S IgM than was found in studies involving predominantly females with SLE (15 18%), and an overall prevalence of IgA deficiency ranging from 0.95% to 4.6%. Males resembled females in the prevalence of Fc-receptor specific reticuloendothelial system dysfunction, correlating with levels of circulating immune complex-like material and disease activity. PMID- 1879086 TI - The pharmacological effects of cicaprost, an oral prostacyclin analogue, in patients with Raynaud's syndrome secondary to systemic sclerosis--a preliminary study. AB - Prostacyclin (PGI2) and its analogues are useful treatments for patients with secondary Raynaud's syndrome (RS). However, they have to be given intravenously, causing inconvenience to patients. Cicaprost is an orally available analogue of PGI2 and has been shown to inhibit platelet aggregation in both in vitro and animal studies. We recently investigated the effects of cicaprost on whole blood platelet aggregation, red cell deformability, white cell function (polymorphonuclear cell aggregation, elastase release and free radical activity) and plasma fibrinolysis in 14 patients with systemic sclerosis (SSc) and secondary RS. Patients received cicaprost (2.5 micrograms or 5 micrograms t.i.d.) or matching placebo tablets orally for 10 days. Blood samples were taken at baseline and 2 hours after administration of the last treatment for the above mentioned assays. No changes were observed in any of the cellular elements and parameters measured in the 3 groups of patients studied. Our study suggests that cicaprost, at doses up to 5 micrograms t.i.d., fails to modify the blood coagulation elements and factors in patients with RS secondary to SSc. Further studies using higher doses and longer study periods are planned. PMID- 1879087 TI - Raised epidermal phospholipase A2 activity in rheumatoid arthritis. AB - Epidermal phospholipase A2 (PLA2) in RA patients was significantly higher than in normals (p less than 0.0001) but lower than in psoriatic patients (p less than 0.05). No relationship was observed between PLA2 activity and commonly used measures of rheumatoid disease activity in a cross-sectional study. However, in a longitudinal study change in PLA2 activity correlated strongly with changes in disease activity. PMID- 1879088 TI - Ischemic encephalopathy in ANA-negative systemic lupus erythematosus. AB - A woman with a nine-year history of Raynaud's phenomenon developed photodermatitis and a sudden neurological syndrome characterized by transient focal disorders accompanied by wide and persistent cerebral lesions demonstrated by CT, NMR and SPECT imaging. A careful evaluation of the clinical manifestations of neurological SLE along with the detection of anti-Ro/SSA antibodies prompted us to reconsider the diagnosis of SLE. Moreover, the discrepancy observed between the poor neurological picture and the widespread encephalic alterations shown by CT, NMR and SPECT imaging suggests that it may be useful to conduct these investigations in patients affected by SLE with modest neurological signs and symptoms. A further interesting aspect of this case is represented by the differential diagnosis with two other diseases, such as Sneddon's syndrome and multiple sclerosis, which are characterized by the presence of certain clinical and instrumental findings also observed in neurological SLE. PMID- 1879089 TI - Dermatomyositis associated with the recurrence of transitional cell carcinomas and Kaposi's sarcoma. AB - A 76-year-old male was admitted to our hospital because of dermatomyositis (DM). Fourteen years earlier a transitional cell carcinoma of the bladder was diagnosed. Following repeated resections of the neoplasm, he was free of the disease for the last two years. Six weeks after starting treatment with steroids and azathioprine for DM, he has developed Kaposi's sarcoma of the skin which subsided upon discontinuation of the immunosuppressive drugs. Four months after the diagnosis of DM, a local recurrence of the bladder carcinoma was found. This patient illustrates the importance of a thorough search for neoplasms or recurrence in elderly patients with dermatomyositis. The case also emphasizes the need for caution in immunosuppressive treatment of autoimmune disorders in such patients. Still, discontinuation of these medications resulted in a significant improvement of the skin neoplasm. PMID- 1879090 TI - HLA class III molecules and autoimmune rheumatic diseases. PMID- 1879091 TI - Evaluation of methotrexate in the treatment of juvenile chronic arthritis according to the subtype. AB - Methotrexate therapy was evaluated in 30 children with juvenile chronic arthritis according to the type of onset. The systemic form seemed less responsive than the ANA positive form with a polyarticular course or polyarticular onset. The clinical improvement, particularly in the ANA positive polyarticular course was confirmed by a significant decrease in the values of the ESR. Side effects occurred in 12 patients and consisted of gastrointestinal upset, mouth ulcers, slight leucopenia and elevated transaminases. They led to discontinuation of the treatment in only one child. Concomitant therapy could be stopped in 50% of the patients with an ANA positive polyarticular course, but remained necessary in the two other groups. These results indicate a differential effect of MTX therapy according to the type of JCA. PMID- 1879092 TI - Chorea as a manifestation of the antiphospholipid syndrome in childhood. AB - Chorea has been related to the presence of antiphospholipid antibodies (a-PL) in the context of systemic lupus erythematosus (SLE). Here we report the case of a 13-year-old girl with a-PL antibodies, who had developed thrombophlebitis at the age of 11 years and chorea two years later, in the absence of clinically evident SLE. Serological tests revealed a false positive test for syphilis, a prolonged activated partial thromboplastin time, hypocomplementaemia and positive anti-DNA antibodies. PMID- 1879093 TI - A limited form of the eosinophilia-myalgia syndrome. PMID- 1879094 TI - Uses and limitations of nuclear magnetic resonance (NMR) spectroscopy in clinical pharmacokinetics. PMID- 1879097 TI - The spectrum of eosinophilic gastroenteritis. Report of six pediatric cases and review of the literature. AB - Eosinophilic gastroenteritis is an inflammatory disease of unknown etiology characterized by infiltration of the gastrointestinal tract with eosinophilic leukocytes, accompanied by varying abdominal symptoms and usually by peripheral blood eosinophilia. We report our experience with six pediatric cases presenting to the Cleveland Clinic Foundation over the past eight years. Unusual findings in our patients included ascitic fluid without eosinophilia and eosinophilic pericarditis (one patient), and eosinophilic cholecystitis (one patient). Endoscopic examination and biopsy helped to establish the diagnosis in all patients. Bone marrow aspiration supported the diagnosis by demonstrating eosinophilia and identifying reactivation of the disease, even in cases without peripheral eosinophilia. All six patients responded promptly to prednisone. Diagnosis is challenging and eosinophilic gastroenteritis may be more common than is recognized. This series of cases significantly expands the spectrum of the disease in children, and documents the usefulness of diagnostic endoscopy in this condition. PMID- 1879098 TI - Multiple personality disorder: a risk indicator, diagnostic marker and psychiatric outcome for severe child abuse. AB - Recent studies suggest that multiple personality disorder (MPD) is not as rare as previously believed. Indeed, it may represent a relatively common (as many as 25% of cases) outcome of severe physical and sexual abuse of children. Because diagnosis and treatment offer the best prognosis, it is important for the pediatric clinician to become familiar with both the at risk situations (such as cult practices and multigenerational sexual abuse) as well as the more unusual behavioral presentations of this disorder. PMID- 1879096 TI - Pharmacokinetics of newer drugs in patients with renal impairment (Part II). AB - Cardiovascular diseases occur frequently in patients with renal failure. Any pharmacokinetic impairment in these diseases should be considered when individualizing drug therapy. The pharmacokinetics of new cardiovascular drugs in uraemic patients are reviewed: alpha- and beta-blocking agents, ACE inhibitors, centrally acting antihypertensive agents, calcium antagonists, antiarrhythmic agents and inotropic agents. Guidelines are proposed for adjustment of dosage regimens as a function of renal impairment. Renal or extrarenal elimination of drugs and their metabolites, and the activity of the latter, are taken into account. The disposition of new drugs such as flestolol, alacepril, delapril, propafenone, milrinone or enoximone, is not well documented in patients with renal failure. Further characterizations of the elimination of these compounds are needed and the potential therapeutic or toxic effects of the metabolites require evaluation to determine whether the dosage needs to be adjusted. Until such investigations are performed, those drugs should not be used in uraemic patients; if no therapeutic alternative is available, clinical controls are necessary at regular intervals. Relationships between pharmacological or therapeutic effects and drug plasma concentrations should be evaluated for such long term use drugs. The knowledge of a plasma concentration therapeutic window is important to provide information which will be useful in determining appropriate drug dosage in renal failure. PMID- 1879099 TI - Pain in neonatal circumcision. AB - Because newborn circumcision is a quick and safe surgical procedure, any method to relieve pain must be almost risk-free in order to be acceptable. General anesthesia and narcotic analgesia are not appropriate. Dorsal penile nerve block (DPNB) with lidocaine hydrochloride is probably the most effective and safest form of anesthesia for newborn circumcision currently available, but it can cause significant local and systemic reactions. Only a limited number of cases of DPNB have been reported and we feel that this procedure should be used cautiously until there is more published evidence of its safety. Alternative methods of pain relief including oral acetaminophen and topical anesthesia should also be studied. Of special interest is recent evidence that a sucrose-flavored pacifier is an effective analgesic during newborn circumcision. PMID- 1879095 TI - Ethnic differences in drug disposition and responsiveness. AB - Interethnic differences are important factors accounting for interindividual variations in drug responsiveness. However, these differences in drug response have been a relatively neglected area of investigation, so that similar doses are prescribed to different ethnic populations without consideration of interethnic pharmacokinetic and pharmacodynamic variation. With the increased recognition of genetically determined polymorphism in metabolising ability as an important factor in drug disposition, concern has developed for the importance of individualising drug dose to account for racial differences. The recognition of these differences in drug disposition and responses calls into question the failure of drug licensing authorities to demand information on dosage, efficacy and toxicity in different ethnic groups, and to accept data from limited ethnic groups such as Caucasians. This article reviews the evidence for ethnic differences in drug disposition and sensitivity and should encourage further investigations to elucidate the extent of such differences, their causes and their therapeutic impact. PMID- 1879100 TI - Gastroesophageal reflux in the older child: presentation, response to treatment and long-term follow-up. AB - Much attention has been focused on the natural history of gastroesophageal reflux (GER) in neurologically normal infants which generally resolves by two years of age. In contrast, little is known of the outcome of GER diagnosed in normal older children. The charts of 32 children (21 males) without neurologic or esophageal anatomic abnormalities, age 3.5 to 16 years (mean = 9.8) at the time of diagnosis, were reviewed. Diagnosis was based on suggestive presenting symptoms and evaluation of prolonged intraesophageal pH monitoring. Esophagitis was diagnosed by histologic criteria in 16 of the 32 patients. Medical treatment consisted of prokinetic agents (metoclopramide, bethanechol) and H2-receptor antagonists. After a one to eight year follow-up period (mean +/- SD - 3.4 +/- 2.1), the symptoms in 13 children had resolved or were sufficiently improved to discontinue medication. In 13 patients, symptoms were improved but medication was required for adequate control. Four children were symptomatic without improvement in spite of medical therapy and two others required fundoplication for continued severe symptoms and refractory esophagitis. In summary, less than 50% of otherwise normal older children with GER undergo spontaneous resolution of marked improvement in symptoms and the remainder require continued long-term medical and/or surgical management. PMID- 1879101 TI - The effect of beta blockade on stress-induced cognitive dysfunction in adolescents. AB - Test anxiety is severely disabling to students whose fear of examinations causes cognitive dysfunction that paralyzes their thinking the way stage fright impairs actors ability to act. In studies using subjective evaluations among actors and musicians, beta-blockade relieved stage fright and has been used informally to treat test anxiety in students without objective measures of effectiveness. The Scholastic Aptitude Test (SAT) was chosen as an objective test instrument to confirm the effect of beta-blockade on test anxiety and performance. Thirty-two high school students who had already taken the SAT before enrolling in this study and who had stress-induced cognitive dysfunction on exams were given 40 mg of propranolol one hour before they retook those tests. Mean SAT scores with beta blockade were 130 points higher than on the initial SAT done before entering the study without medication (p = less than .01). A single dose of propranolol immediately before the SAT permitted improved performance in students prone to cognitive dysfunction due to test anxiety. PMID- 1879102 TI - "The effect of beta blockade on stress-induced cognitive dysfunction in adolescents". PMID- 1879103 TI - The value of the autopsy in congenital heart disease. AB - We reviewed autopsies in 50 consecutive cases of congenital heart disease between 1980 and 1988. Autopsy results were compared to premortem clinical diagnosis. The patients ranged in age from two days to 66.5 years with a mean age of 6.42 years; 68% were less than one year of age. The most common diagnoses were hypoplastic left heart syndrome in 16 (32%) and ventricular septal defect in five (10%). Other common diagnoses included coarctation of the aorta, hypoplastic right heart syndrome, tetralogy of Fallot, transposition of the great vessels and tricuspid atresia. No patient had a missed diagnosis that would have changed survival (Class 1). Four (8%) of the patients had one missed major diagnosis that did not change their survival because they were already being symptomatically treated or because no clinical treatment was available (Class 2). The majority of autopsy derived data were missed minor diagnoses that were related [14 (28%)-Class 3] or unrelated [12 (24%) - Class 4] to the terminal disease process. However, despite the small percentage of autopsy findings that would have directly affected survival, the autopsy provided important additional clinical information in 30 (60%) patients. This information could be used to correct management errors and to develop protocols for prophylaxis against known complications. The pediatric autopsy can provide useful clinical data that may be a guide to altering clinical therapy and is essential in providing genetic counseling. PMID- 1879105 TI - Neonatal sepsis. PMID- 1879104 TI - Current issues in neonatal herpes simplex virus infection. AB - Significant progress has been made in the recognition and treatment of herpes simplex disease in the newborn. This review discusses four current issues surrounding this severe and important infection. First, the reasons underlying the failure of antenatal screening programs to identify high-risk pregnancies for herpes simplex are analyzed. Second, typical and atypical clinical manifestations of neonatal herpetic infection are reviewed. Third, determinants of disease, particularly the immune status of the mother and child, and their therapeutic implications are discussed. Finally, controversies surrounding antiviral therapy are examined. PMID- 1879106 TI - Perinatal human immunodeficiency virus infection. AB - Infection with HIV is rarely clinically apparent in the newborn period. At present, there is no satisfactorily sensitive and specific test to diagnose infection in the newborn nursery. Identification of women at risk for transmission of HIV to their infants and of infants at risk for vertically transmitted HIV infection, so that early diagnosis and treatment can be instituted, is the currently recommended approach. PMID- 1879108 TI - Neonatal candidiasis: the current challenge. AB - The current challenge of neonatal candidiasis arises from the increased survival of very low birthweight infants. It is important to understand those factors affecting normal colonization of the neonate, concomitant with those factors that predispose to fungal invasiveness. Disseminated candidiasis may present with subtle signs and symptoms, but has the potential for a wide variety of organ system involvement. Early initiation of aggressive therapy, with careful monitoring, can lead to a successful outcome. PMID- 1879107 TI - Perinatal mycoplasmal infections. AB - Maternal infections are known to play a major role in perinatal morbidity and mortality. Ureaplasma urealyticum and Mycoplasma hominis are sexually transmissible microorganisms associated with a number of pathologic conditions in the pregnant woman including chorioamnionitis and postpartum fever. They are rapidly gaining recognition as significant causes of perinatal infection, especially in infants born prematurely. This review summarizes current knowledge regarding the epidemiology, pathology, disease spectrum, and clinical manifestations of mycoplasmal and ureaplasmal perinatal infections and presents guidelines for proper diagnosis and treatment. PMID- 1879109 TI - Coagulase-negative staphylococcal infection in the neonate. AB - During the last decade, improved neonatal care has permitted the survival of extremely low birthweight infants who are at increased risk for the development of nosocomial infection. The coagulase-negative staphylococci currently represent the most frequent nosocomial pathogen isolated from infants in the newborn intensive care unit. This article details pathogenesis, clinical manifestations, diagnosis, treatment, and prevention of neonatal infection with this organism. PMID- 1879110 TI - Rational principles for immunoglobulin prophylaxis and therapy of neonatal infections. AB - Immunotherapy was a common method of treating infectious diseases in the preantibiotic era. Serotherapy was a popular approach to serious infections and employed hyperimmune globulins harvested from various large animals. Such antisera needed to be administered early in the course of the disease and unfortunately was associated with significant risks of anaphylaxis and serum sickness. Because of the allergic risks associated with animal immunoglobulin preparations, the development of methods to isolate human immunoglobulins heralded a new era in immunotherapy. This article examines the uses of immunotherapy in the treatment of neonatal infections. PMID- 1879111 TI - Therapeutic administration of fibronectin: current uses and potential applications. AB - Fibronectins are a class of multifunctional glycoproteins that exist in soluble and insoluble forms. These glycoproteins are found in nearly all body fluids and in tissue extracellular matrices. Alterations in the normal synthesis, release, and distribution of fibronectins are characteristic features of certain human pathophysiologic conditions. The therapeutic administration of plasma fibronectin to human patients with defects in corneal wound healing and critically ill adult patients with multisystem organ failure appears clinically beneficial, although confirmation is needed from additional trials in progress. In vitro data suggest a role for fibronectin in enhancing (directly and indirectly) the function of phagocytes isolated from the blood of newborn infants. Although as yet untested, it is possible that fibronectin administration to the immunologically immature human neonate may improve host defenses and reduce the risk of nosocomial infection. Additional research is needed to define the factors that regulate the synthesis, isoform expression, and clearance of endogenous fibronectins during normal fetal and neonatal development. Continued research to define the role of endogenous fibronectins in augmenting the inflammatory response of the neonatal host is also required before rational immunotherapeutic interventions can be initiated. PMID- 1879112 TI - Cytokines: a new immunotherapy. AB - Numerous abnormalities in neonatal host-defense mechanisms have been documented over the past decade. Profound disturbances in myeloid progenitor proliferation, bone marrow neutrophil storage pools, a tendency to peripheral neutropenia and significant in vitro abnormalities of mature neutrophil cell effector function all predispose the neonate to a high mortality rate during bacterial sepsis. The recent use of hematopoietic CSFs and other cytokines to enhance host defense mechanisms in the adult has suggested a role for this new form of immunotherapy in the newborn. Several studies over the past 2 years have indicated that a number of these cytokines may in fact enhance neonatal myeloid progenitor proliferation, modulate neonatal bone marrow neutrophil storage and proliferative pools, induce peripheral neutrophilia and protect against the high mortality rate associated with experimental bacterial sepsis to enhance neonatal host defense against overwhelming bacterial infection. PMID- 1879113 TI - Clinicopathologic approach to the diagnosis of neonatal sepsis. AB - Perinatally acquired bacterial neonatal sepsis is a low-incidence, high-risk disease with a relatively benign treatment. Accurate diagnosis is difficult because there is no definitive diagnostic test; even blood cultures have an unacceptably low sensitivity. Therefore, the clinician must accept that a number of neonates will have treatment initiated for sepsis who do not have the disease. In order to treat rapidly all infants with sepsis and to minimize therapy for those without infection, historical, clinical, and laboratory data can be used together in a management approach to achieve optimal results. PMID- 1879114 TI - Medical imaging in acute abdominal pain. PMID- 1879115 TI - Role of the central nervous system in stress ulcers. PMID- 1879117 TI - Diagnosis and treatment of gastroesophageal reflux disease. PMID- 1879116 TI - Current drug therapy for inflammatory bowel disease. PMID- 1879118 TI - Immediate and follow-up management of hepatic trauma. AB - There has been a considerable evolution in the management of patients with hepatic injuries in the past 5-10 years. CT is now the mainstay of diagnosis for stable patients with blunt hepatic injuries. This allows for nonoperative therapy in many patients with lacerations, intrahepatic hematomas, or subcapsular hematomas. Simple operative techniques are used in 60% of patients with blunt injuries, and any deaths in this group are usually due to associated injuries. In patients requiring advanced techniques of repair, postoperative management emphasizes basic techniques including correction of hypothermia and coagulopathies and early use of enteral feeding. Postoperative complications are not rare when Class III, IV, or V hepatic injuries have been treated, but can be managed with the assistance of the interventional radiologist, blood bank, or by use of early reoperation. Mortality depends on mechanism of injury and magnitude of hepatic injury, and ranges from 14-31% for patients with blunt trauma. PMID- 1879119 TI - The clinical management of cirrhosis. AB - The discipline of hepatology is being rapidly advanced by several methods of investigation, most notably those of molecular and genetic biology. The polymerase chain reaction holds very great promise in unraveling the implications of hepatic virus infections. At the present time, we have no method of reversing established cirrhosis, and those with life threatening impairment of liver function can only look to liver transplants for salvage. The clinician can therefore best serve by identifying liver disease before cirrhosis and its complications occur. With effective case finding, and the continued development of therapeutic interventions directed toward known or suspected etiologic and pathogenic factors, many productive, high-quality years can be added to the lifespans of many patients. PMID- 1879120 TI - Some practical advice concerning Helicobacter pylori. PMID- 1879121 TI - Advances in etiology, diagnosis, and treatment of gastric disorders. PMID- 1879122 TI - Effort thrombosis of the axillosubclavian vein: a disabling vascular disorder. AB - In the natural history of this disorder, resumption of normal activity after a period of recuperation (following an episode of thrombosis) frequently leads to symptoms of upper extremity venous hypertension exacerbated by using the arms in the overhead position. This position can be demonstrated venographically to further occlude collateral vessels in thoracic outlet. A number of patients develop more extensive symptoms of neurogenic thoracic outlet syndrome. Anticoagulation may protect the collateral vessels and interrupt the period of active clot propagation resulting in a better functional result than would be expected from the natural history of the thrombotic event. In our experience, local Urokinase was the most effective means for reestablishing venous patency. With clot dissolution the underlying compression of the vein at the thoracic outlet can be demonstrated. Balloon angioplasty should not be undertaken in the acute setting nor prior to relieving the tendinous compression. The acute phlebitic process should resolve under the protection of Coumadin for three months. At that time it can be determined more effectively which patients require additional therapy. Removal of the first rib will decompress the axillosubclavian vein and the thoracic outlet collaterals permitting the vein to regain its normal configuration particularly in younger patients with more acute onset of compression. In those patients with more chronic compression the vein becomes stenotic. Improvement of the luminal configuration has been accomplished with transvenous balloon angioplasty without the necessity for venous reconstructive procedures in this series. Patients with Paget-Schroetter syndrome have a symptom complex which often reflects more extensive neurovascular compression at the thoracic outlet than that which might result from venous hypertension alone. Although thrombolytic therapy can restore patency of the axillosubclavian vein, first rib resection is necessary to relieve the external compression. This procedure was very effective in patients who had restoration of subclavian vein patency, and to a lesser degree in those with residual occlusion. PMID- 1879124 TI - On the role of genetic factors in coronary heart disease. PMID- 1879123 TI - Prevention and treatment of pregnancy-induced hypertension. PMID- 1879125 TI - Control of cardiac transplant rejection. PMID- 1879126 TI - Declining mortality from cardiovascular disease. PMID- 1879127 TI - Update: drug therapy for acute myocardial infarction. AB - Acute myocardial infarction is potentially a highly treatable disease. Immediate interventions are directed to decreasing tissue hypoxia with oxygen and improving bloodflow to ischemic myocardium using nitrates and thrombolytic agents. Cardiac workload should be reduced by eliminating endogenous catecholamine release with analgesia and sedation, and beta blockade in patients without CHF to decrease heart rate and myocardial oxygen demand. Treatment of the complications of AMI include dysrhythmia prophylaxis, monitoring and specific therapy. Treatment of pump failure includes using vasodilators, vasopressors and positive inotropic agents. Early recognition and timely initiation of appropriate therapy should be every physician's goal. PMID- 1879128 TI - Update: current role of thrombolytic therapy. PMID- 1879129 TI - The renin-angiotensin system: renal actions and blood pressure regulation. AB - The RAS is part of an extremely powerful feedback system for long-term control of blood pressure and volume homeostasis. Disturbances that tend to lower blood pressure, such as heart failure, cirrhosis, and peripheral vasodilation, cause sodium and water retention until blood pressure returns to normal due, in large part, to the combined actions of ANGII and reduced arterial pressure. In response to increased sodium intake, decreased ANGII formation greatly amplifies the effectiveness of pressure natriuresis, thereby preventing large increases in body fluid volumes and blood pressure. In circumstances in which the RAS is inappropriately activated, the sodium retaining effects of ANGII necessitate increased blood pressure to maintain sodium balance via pressure natriuresis. Because the RAS is so powerful in regulating blood pressure, blockade of the system with ACE inhibitors offers a powerful therapeutic tool in diseases such as hypertension and congestive heart failure. The control of sodium excretion and blood pressure by ANGII is exerted through multiple intrarenal as well as extrarenal effects, including stimulation of aldosterone secretion, which can influence renal excretion. Current evidence suggests that the intrarenal effects of ANGII are quantitatively more important than those mediated by aldosterone in controlling blood pressure and renal excretion. The most important intrarenal effects of ANGII include efferent arteriolar constriction as well as direct effects on sodium transport. The constrictor effect on efferent arterioles also is important in preventing reductions in GFR in circumstances associated with impaired renal perfusion. Therefore blockade of ANGII formation in circumstances such as renal artery stenosis may caused marked reductions in GFR. However, in many patients efferent arteriolar vasodilation caused by ANGII blockade may not lower GFR markedly because of other autoregulatory mechanisms that compensate by causing parallel reductions in afferent arteriolar resistance. In these individuals, chronic ACE inhibition may prove to be beneficial in slowing the progression of renal disease because a reduction in glomerular hydrostatic pressure may help to prevent glomerular damage. PMID- 1879130 TI - Image operations in quantification of atherosclerosis from digitized angiograms. AB - This report describes a method of quantifying the inner volume (lumen volume) of a contrast medium-filled femoral artery from a roentgenogram by computerized image analysis. The various factors influencing the accuracy of the volume determination are analyzed and an image-processing procedure for the elimination of artifacts due to crossing arteries is described and evaluated. The presented methods have been used in a large study of 281 patients and the short-term reproducibility has been found to be 1.00. PMID- 1879131 TI - A PC data-base with analytical applications for evoked potentials. AB - Visual Evoked Potentials (VEPs) are gaining ground in the research for diagnosis of neurological disorders and visual defects, as a non-invasive diagnostic tool. Yet, the methods used towards these goals are not universal and far from able to provide a common ground among researchers in collecting, analyzing and comparing their results. This paper is an attempt to close the gap. We have developed a PC data-base and a set of analysis programs with graphic capabilities, frequency analysis, as well as an objective way of describing the signals obtained during VEP experiments. PMID- 1879132 TI - A full-to-empty mode controller for the pneumatically-driven blood pump. AB - Presented in this paper is a microprocessor-based controller developed based upon the theory of finite state automata to activate the pneumatically-driven diaphragm blood pump in the full-to-empty mode. Under normal situations, each pumping cycle of the blood pump can be divided into several phases in a proper sequence, and such phase information is contained in the driving air pressure waveform. The controller tries to match the sequential phases with the pressure waveform sampled at real time in an attempt to search for the end-ejection or end filling of the blood pump. If either the end-ejection or the end-filling can be found, the controller sends triggering signals to the driving unit, and if the sampled pressure waveform can not be matched with the sequential phases or the controller fails to detect the end-ejection or end-filling, the controller activates the driving unit by the parameters of the last measured pumping cycle; thus, the driving unit triggers the blood pump without any stop. The result of laboratory bench tests demonstrates its ability in finding the end-ejection and end-filling points and the reliability of the fail-safe measure. PMID- 1879133 TI - Precision of hemodialysis urea kinetic modeling: empirical data and Monte Carlo simulation. AB - To examine the precision of variable volume urea kinetic modeling (UKMv) 15 stable hemodialysis patients were followed with repeated sampling for 5 weeks. Samples were frozen and later submitted to careful batch analysis. On average, the index for dialysis adequacy (Kt/V) varied 6.1% and normalized protein catabolic rate (pcr) varied 10.5%. Immediate routine analysis correspondingly rendered 8.6% and 13.2%. A simpler, fixed volume model (UKMf) had an almost similar variation and results correlated highly with UKMv. The duration of the preceding interval does not affect Kt/V, but per is lower during longer intervals. Computer simulation demonstrated that most of the variation of calculated pcr could be explained by fluctuations of urea generation, i.e., secondary to dietary changes. Fluctuations in the efficiency of dialysis may cause most variation of Kt/V, but the imprecision of the urea analysis also contributes. Precise knowledge of effective dialyzer clearance is not important for the calculation of Kt/V and pcr. It is concluded that calculating these variables with a simple model, employing a reasonable estimate of dialyzer clearance will suffice for routine use. The slightly higher accuracy of a more sophisticated model is overshadowed by day-to-day variations. PMID- 1879134 TI - Identification of peptides within a known protein sequence using COMSEQ analysis of data containing multiple sequences. AB - Modern methods of automated protein sequence analysis can provide high-quality data with which unambiguous amino-acid sequences can be determined, but analyses are more difficult when the sample is not pure. COMSEQ and auxillary programs were written to facilitate reconciliation of multiple amino-acid sequences potentially contained in noisy data with the known amino-acid sequence of the parent protein. The COMSEQ program prints a matrix in which the first vertical column represents the known amino-acid sequence of a selected protein. Each row of the matrix contains the sequencer yield corresponding to the amino acid in the first column, with each column corresponding to the sequencing reaction cycle. A diagonal which contains net increases of amino acids for each amino acid in the known sequence identifies a peptide potentially contained within the data. The number of matches for each diagonal over the entire known sequence are tabulated and presented as an aid to locating comparisons of greatest interest. The RNDSEQ program conducts multiple analyses using randomized versions of the known amino acid sequence and tabulates the cumulative frequencies of potential sequence matches irrespective of the true known sequence. TRANSEQ is a utility program that translates edited sequence data from common databases into files that can be used by COMSEQ and RNDSEQ. The programs have been used successfully to identify two co-sequenced peptides from bovine serum albumin, an albumin peptide sequence in the presence of hemoglobin, and to identify two sequences of rat alpha-2u globulin that differ in their amino termini. PMID- 1879135 TI - Randomization tests: statistics for experimenters. AB - Randomization (permutation) tests free the experimenter from the constraints of random sampling, a known error distribution and equal variances, to give a direct answer to the question "how likely is such a large (or small) result if the applied treatments had no effect?" The "result" may be the difference in mean responses, a correlation coefficient or any other value of interest. A randomization test is not a different statistical test but a different, and always valid, method of determining statistical significance. The familiar t-test and F-test can be carried out by data permutation without any parametric assumptions being fulfilled. A particular advantage of this method is that unbalanced designs and missing values are easily accommodated. Even with only a small number of subjects the number of permutations will be large and a computer is necessary if the randomization test is to be of practical value. To make this method of determining statistical significance generally available an interactive microcomputer program, forming a comprehensive package for the design and analysis of experiments, has been prepared. PMID- 1879136 TI - Algorithm for point-to-point correlation of geometrically nearly similar microscopic objects. AB - An algorithm is presented that compares two quasi similar images by correlating selected points on them--assuming their coordinates are available. The procedure involves translational, magnificational and rotational operations to find corresponding point pairs on the pictures. The algorithm automatically compensates for slight dissimilarities between images and constructs a reference point database for correlation during the evaluation process. Establishment of the reference point networks on the images prior to the examination is avoided. PMID- 1879137 TI - A structured visual language for a knowledge-based front-end to statistical analysis systems in biomedical research. AB - Within the last few years, several knowledge-based systems for statistical analysis systems have been proposed (see Refs. 1-4 for references). Most of these systems provide so-called 'natural-language' interfaces for acquisition and application of meta-data. Since graphics have been very efficient in displaying results (e.g., as scatter, QQ and residual plots), some attempts have been made (cf. Refs. 5,6) to use graphics also to display knowledge of the statistical strategy. In the present paper I will concentrate on the visualization of knowledge of the experimental design and its impacts on the design of a structured visual syntax language for acquisition and application of this knowledge in the field of biomedical research. PMID- 1879138 TI - The role of endometrial swabs in the diagnosis (and pathogenesis?) of endometritis. PMID- 1879139 TI - Bone abscess in the mandible of a quarter horse gelding. AB - A 4-year-old Quarter horse gelding presented with a swelling in the soft tissues over the junction of the body and ramus of the left mandible. Radiography showed a well circumscribed lytic area within the mandible surrounded by sclerosis unassociated with any tooth. Aspiration of the lesion yielded pus. The abscess cavity was opened, curetted and lavaged. A Penrose drain was placed in the abscess cavity for 10 days. Bacteriological culture of the exudate and soft tissues from the abscess produced a few colonies of Staphylococcus intermedius. Histopathology showed chronic pyogenic infection. The horse recovered well and was normal 1 year after treatment. PMID- 1879141 TI - Prolonged gestation in a Holstein cow: adenohypophyseal aplasia and skeletal pathology in the offspring. AB - A Holstein fetus was delivered by Caesarean section at a gestational age of 441 days. The pituitary pars distalis was aplastic and the adrenal and thyroid glands were severely hypoplastic. Arrested or retarded cartilage cell maturation resulted in absence or minimal development of epiphyseal ossification centers, delayed ossification of carpal bones, and arrest of longitudinal growth of bones. The pathophysiology of prolonged gestation and of skeletal pathology is discussed. PMID- 1879140 TI - Dexamethasone reduces endotoxin-induced tumor necrosis factor activity production in vitro by equine peritoneal macrophages. AB - This study evaluated the effect of dexamethasone on endotoxin-induced production of tumor necrosis factor (TNF) activity in vitro by equine peritoneal macrophages. Peritoneal macrophages from adult horses were cultured in the presence of dexamethasone (1-100 microM) for various time periods (2 hour, 0.5 hour, 0 hour) prior to the addition of endotoxin (5 ng/ml), then the secretion of TNF activity was evaluated. Macrophage supernatant concentrations of TNF activity were estimated by a modified in vitro cytotoxicity bioassay using the murine fibrosarcoma cell line, WEHI 164 clone 13. An experiment was performed to determine whether dexamethasone interfered with the cytolytic bioassay's ability to detect TNF activity. The endotoxin-induced TNF activity production by equine peritoneal macrophages was significantly reduced by co-incubation with 100 microM dexamethasone, but not by tested concentrations of dexamethasone less than 100 microM. This concentration of dexamethasone greatly exceeds those generally attained by therapeutic use of dexamethasone in horses. Preincubation time did not affect the ability of 100 microM dexamethasone to reduce TNF production by equine macrophages. The quantitation of equine TNF activity by its cytolytic bioassay was not altered by dexamethasone. PMID- 1879142 TI - Squamous cell carcinoma as a cause of dyspnea and blindness in a horse. AB - An 8-year-old Quarter Horse mare was examined for chronic nasal discharge and obstruction of both nasal passages. A solid mass lesion was identified in the maxillary sinuses, soft palate, nasal and pharyngeal cavities. Palliative surgery was used to debulk the lesion and facilitate nasal airflow. Squamous cell carcinoma was diagnosed from surgical biopsies. Approximately 7-8 weeks after surgery, the mare was observed to be acutely blind. Ophthalmologic examination revealed central origin blindness and active retinitis. The squamous cell carcinoma had reobstructed the nasal passages. Pressure by the expanding tumor deformed the ethmoid and sphenoid bones resulting in compression of the optic tracts. No bony invasion by the tumor was present. PMID- 1879143 TI - Unilateral optic nerve hypoplasia and hydrocephalus in a Pekingese. AB - A 3-year-old, castrated male Pekingese was examined 2 days after automobile induced trauma. Multiple pelvic injuries and visual deficits in the right eye were identified. During a subsequent postmortem examination, multiple pelvic fractures were confirmed; however, there was no evidence of head injury. Both globes were bilaterally symmetrical and grossly normal. The intraorbital and intracranial portions of the right optic nerve were threadlike and rudimentary in appearance, while the left optic nerve was grossly normal. Moderate dilatation of the left lateral ventricle was noted. Microscopically the right optic nerve and left nerve tract contained few identifiable nerve fibers. The right optic disc was depressed, and there was thinning of the optic nerve fiber and ganglion cell layers of the retina. No microscopic abnormalities were evident in the left optic nerve, optic disc, retina and right optic tract. The histologic changes in the right eye are consistent with optic nerve hypoplasia. The relationship between the optic nerve/optic tract lesions and the hydrocephalus is unknown. PMID- 1879144 TI - The bovine oviduct and its role in reproduction: a review of the literature. AB - The bovine oviduct provides the environment for sperm transport and capacitation, oocyte transport and maturation, fertilization and early embryonic cleavage. Gamete interactions in the tube occur in contact with both the tubal epithelium and the oviduct fluid secreted by these cells. Current research continues to reveal the active role of the oviduct and its products play in normal fertilization and embryo development. This paper reviews the anatomy and physiology of the oviduct of the cow, including the specific events of reproduction which occur in this organ. PMID- 1879145 TI - Disseminated infection with Neospora caninum in a ten-year-old dog. AB - Naturally-occurring neosporosis with multiple organ involvement was identified in a 10-year-old neutered male Basset hound dog. Clinical signs were first noticed 3 weeks prior to referral and consisted of crouched stance and mild pelvic limb ataxia. Dexamethasone administration had provided transient improvement. On presentation to the teaching hospital, clinical signs included depression, pelvic limb ataxia, inability to stand without assistance, and pain on deep palpation of the cervical and lumbar vertebral column. Lesions were found in the myocardium, liver, spleen, adrenal glands, brain, and spinal cord. Tachyzoites of Neospora caninum were found in the myocardium and adrenal glands. Organisms stained with anti-Neospora caninum, but not to anti-Toxoplasma gondii serum in an immunohistochemical test. PMID- 1879146 TI - A role for the left hemisphere in spatial processing. AB - This study extended our recently reported evidence of a left hemisphere (LH) contribution to spatial processing on standard visuospatial tasks. The present investigation compared performance on these standard tasks with that on 'purer' experimental tasks. Two tasks of line orientation, two of shape rotation and a shape matching task were administered to 50 men with stable unilateral post Rolandic missile injuries and 32 control subjects. A LH deficit was found on the standard task of line orientation but not the 'purer' task, suggesting that the LH plays a role in eliminating extraneous information, presented only in the standard test. As for shape rotation, the LH group was impaired on both tasks. On the shape matching task, both experimental groups were significantly slower than control subjects. It is proposed the LH makes an important contribution to mental rotation and the understanding of Euclidean geometrical shapes. PMID- 1879147 TI - Case studies in working memory: a case for single cases? AB - Patterns of cognitive deficit in single neuropsychological cases are common sources of evidence for theories of normal cognition. In particular, the working memory model has benefited from data obtained from a number of contrasting patients, in some cases resulting in modifications of the working memory model. In this paper, patterns of data from short-term memory patients and anarthric patients are compared with patterns of data from normal subjects. The patterns of patient data that were unlike those patterns typically found for groups of normal subjects, could be incorporated within a modified version of the articulatory loop component of the working memory model. However a small number of individual normal subjects also did not show the pattern that is reported on the basis of average performance of groups of normal subjects. This causes some difficulty in interpreting those data from such 'aberrant normal' patterns, and those data from single patients with functional cognitive deficits. The implications of these findings for the interpretation of neuropsychological data are discussed in the context of the working memory model, but with the intention of making a general point pertaining to the development of functional models of cognition. It is argued that single case studies should continue to provide a useful source of evidence, providing that care is exercised in considering the implications of such data for models of normal cognition. PMID- 1879148 TI - Right hemisphere advantage for evaluating emotional facial expressions. AB - The ability to evaluate the intensity of emotional facial expressions was investigated in patients undergoing the intracarotid sodium amytal procedure. It was found that when the hemisphere non-dominant for language (usually right) was anesthetized, the patients' ratings of the intensity of emotional expressions in photographs were lower than baseline ratings of these expressions. Such an effect was not seen with anesthetization of the hemisphere dominant for language (usually left). Ratings of shades of gray (which served as control stimuli) showed no such effect. The findings are interpreted in terms of a right hemisphere superiority in the perception and evaluation of emotional expression. PMID- 1879149 TI - Mental programming after frontal lobe lesions: results on digit symbol performance with self-selected goals. AB - The aim of this study was to demonstrate that the inability to set adequate sub goals in a cognitive task is a sensitive indicator of programming deficit after frontal lobe lesion. Sixty-one patients with focal cerebral lesions and 25 control subjects were studied with a modified Digit Symbol task, in which the score depended on the adequacy of the sub-goals set by the subject. This score was compared to that on the standard condition, in which the subject was requested to work as quickly as possible without self-selected goals. The results confirmed the prediction that patients with anterior lesions set less adequate sub-goals than patients with posterior lesions and, unlike the latter patients, have a more pronounced deficit on the performance with self-selected goals than on the standard condition. In particular patients with left frontal lobe lesions underestimated their capabilities in relation to task requirements. PMID- 1879150 TI - Apperceptive and associative forms of prosopagnosia. AB - Three prosopagnosic patients were given four face tests, two perceptual (an unknown face identification test and an age estimation test) and two also implying memory (a familiarity check test and a famous face recognition test). The patients' performance was assessed with reference to the score distribution of the normal population. A patient was found to fail both perceptual and mnestic tests, without any noticeable difference between them. Also the second patient had poor scores on both kinds of tests, but his impairment was significantly greater on the perceptual ones. The third patient, on the contrary, showed no perceptual deficit and only failed the mnestic tests. His inability to recognize the individuality of an item among members of the same category was strictly confined to faces and never present for other classes of stimuli (cars, coins, personal belongings). This finding is supportive of the thesis that in a few patients the deficit underlying prosopagnosia is face specific. PMID- 1879151 TI - Handedness effects in the detection of dichotically-presented words and emotions. AB - Left-handed and right-handed subjects were given two dichotic listening tasks using identical material. In one task, they were asked to determine whether or not a specific target word was present (verbal task). In the other task, subjects were asked to indicate whether or not one of the dichotically-competing words was spoken in a particular affective tone (emotion task). Overall, a right-ear advantage (REA) was found with the verbal task and a left-ear advantage (LEA) with the emotion task. Left-handers showed a slightly smaller REA than right handers on the verbal task, but a slightly larger LEA on the emotion task. This finding suggests that left- and right-hemispheric functions are not related in a complementary fashion and that handedness effects for nonverbal tasks are different from those seen with verbal tasks. The emotional LEA was much larger for angry stimuli than for happy, sad, or neutral stimuli. Rather than providing evidence for a hemisphere by affective valence interaction, such results suggest a stimulus-specific effect. PMID- 1879152 TI - The effect of contextual constraint on semantic judgments by Alzheimer patients. AB - Subjects (Alzheimer patients, normal young and elderly individuals) heard a sentence the last word of which was missing. A visual word then appeared and the subjects decided whether it made a sensible ending to the sentence. Sentences varied in the degree to which their semantic context constrained possible endings to the sentence. The degree of contextual constraint greatly influenced response time--the greater the constraint, the faster subjects made their decisions. While Alzheimer patients were slower than normals, their decision time was affected by contextual constraint to the same degree as that of normals. Thus, the performance of Alzheimer patients was sensitive to the amount of semantic context present in sentences, and this context facilitated their ability to make conscious semantic judgements. These findings suggest that Alzheimer patients are capable of using semantic information in a task requiring attention-dependent processes. PMID- 1879153 TI - Right brain damage impairs recognition of negative emotions. AB - Patients with right or left hemisphere-damage and normal control groups were asked to judge facial emotions from photographs presented in two orientations- upright, inverted. Responses were elicited with a matching and a verbal labelling task. Normal controls were significantly superior in the judgment of facial emotions than left hemisphere-damaged patients, who in turn were significantly superior than right hemisphere-damaged patients. Negative-aroused (fear, anger) and negative-nonaroused (sadness, disgust) facial expressions were recognized with significantly greater accuracy by left hemisphere-damaged patients compared to right hemisphere-damaged patients; the group difference in performance was nonsignificant for positive (happiness, surprise) emotions. PMID- 1879154 TI - Strategies in comprehension of relative clauses by parkinsonian patients. AB - Twenty patients with Parkinson disease (PD) and twenty normal control subjects (NC) matched on age, sex, education and socio-economic status (SES) were tested for comprehension of four types of relative clauses with complex thematic roles (syntax) and no semantic and pragmatic constraints (reversible) in a sentence picture matching task. The results show a clear language impairment for PD patients compared to NC. Additional evidence from testing school children in grade 1 (G1) and grade 6 (G6) indicates that G1 children perform similar to PD patients and G6 children perform as high as NC. The overall picture of the findings suggests: (1) PD patients process sentences with complex thematic roles and semantic reversibility on a heuristic and not on an algorithmic basis, a type of behavior assumed to be associated with frontal lobe dysfunction; (2) PD patients display some patterns of language behavior similar to those observed in aphasics. Similarities in language behavior between PD patients and G1 children are discussed with regard to the "regression hypothesis" (Jacobson, 1968). PMID- 1879155 TI - Handedness for eating in gorillas. AB - Observations of spontaneous reaching for food in 31 captive lowland gorillas found a full range of hand preferences between strong left and strong right, with most animals showing intermediate levels of preference. There was a high degree of consistency between observations made on different occasions for the same animal, showing that degrees of relative preference tend to be stable in individuals. The findings agree with the majority of previous studies of apes and other primates in showing no species bias to one side, with about half the animals left and half right preferent. PMID- 1879156 TI - A study of plane bisection in four cases of visual neglect. AB - We report four case studies of bisection performance in patients with severe left neglect consequent upon right hemisphere lesion. The stimuli to be bisected range from a horizontal line through horizontally oriented rectangles to a square; the stimuli are displayed on a VDU and bisections made by moving a 'mouse' that controls a cursor line on the screen. For one of the patients, both the starting position of the cursor (left or right) and the shape of the stimulus have a major effect upon bisection accuracy. One patient shows an effect of starting position but not stimulus geometry; two patients show an effect of stimulus geometry but not starting position. For 3 out of 4 patients, the estimated midpoint of a line is thus not equivalent to that of a plane with the same horizontal extent. A putative 'attentional' interpretation of the results is provided. PMID- 1879157 TI - Brain activation during a linguistic task in conduction aphasia. AB - In order to investigate functional cortical reorganization during recovery from conduction aphasia, regional cerebral blood flows (rCBF) were measured by the two dimensional 133 Xenon inhalation method in ten stroke patients. rCBF measurements were performed at rest and during the performance of a linguistic task, one month and three months after onset. The analysis of flow changes from rest to test condition indicates an increasing contribution of the right hemisphere as time goes on. The absence of flow increase in Broca's region suggests that this region is definitively disconnected from posterior language "centers" by the arcuate fasciculus lesion. PMID- 1879158 TI - Hand preference in homosexual men. AB - The present study examined the distribution of hand preference and its relationship to immune system functioning and performance on neuropsychological tests in a sample of 993 homosexual men from the Multicenter AIDS Cohort Study comprising 502 HIV-1 seronegatives, 436 asymptomatic HIV-1 seropositives, and 55 men with diagnoses of AIDS or AIDS Related Complex. The prevalence of left handedness in all of the groups (13.1-14.5%) was consistent with prior published reports of prevalent left-handedness in the general population. The distribution of hand preference scores (on a 5-item self-report questionnaire) was J-shaped and shifted to the right as in the general population. There were no differences between right- and left-handers in the immune system parameter of CD4 counts, nor was there any increase of self-reported allergies among the left-handers. We found a significantly larger number of 'outliers' on the neuropsychological measures for left-handers than for right-handers, both for HIV-1 seronegatives and seropositives. These results failed to replicate Lindesay's (1987) report of a leftward shift in manual preference among homosexual men, and failed to support Geschwind and Galaburda's (1985b) hypothesis of a link between homosexuality, handedness and autoimmune disorder. The differences between right- and left handers on neuropsychological measures, independent of HIV-1 serostatus, are discussed in terms of Satz's (1972) model of pathological left-handedness. PMID- 1879159 TI - Varieties of sentence comprehension deficits: a case study. AB - In recent publications, Grodzinsky (1984, 1986, 1990) has offered a new theory of the disruption of sentence comprehension in so-called agrammatic aphasics. In these works Grodzinsky contends that his account, which is based in various ways on the formal apparatus of current syntactic theory (Chomsky, 1981), is an accurate and explanatory characterization of the preserved language of all those who present with both agrammatic sentence production and asyntactic sentence comprehension. We argue that this claim is not in accord with the facts. We present a detailed case study of the sentence comprehension performance of a patient who is clinically categorized as agrammatic. This patient's performance on full and truncated passives, and on subject- and object-cleft sentences fails each of Grodzinsky's predictions for these sentence types. We argue that whether there exists any patient who does exhibit the predicted performance pattern is also in serious doubt. PMID- 1879160 TI - Long-term recency effects and phonological short-term memory. A neuropsychological case study. AB - Long-term recency effects were investigated in a left brain-damaged patient, PV, who had a pathologically low auditory-verbal span and a lack of the normal recency effects in immediate free recall of auditorily presented lists of words, attributed to the abnormally reduced capacity of the phonological short-term store component of memory (Vallar and Papagno, 1986). In a task requiring the delayed free recall of a list of anagram solutions the patient showed both a recall performance level and a long-term recency effect comparable to the control group. These findings dissociate long and short-term recency phenomena, which would reflect the operation of different memory components. A collateral finding was PV's difficulty in anagram solving, which may be traced back to the defective function of her phonological short-term store. PMID- 1879161 TI - Disturbances of cross-localization of fingertips in a callosal patient. AB - If defective cross-localization of fingertips (CLF) in callosal patients is due to a deficit in the interhemispheric transfer of somesthetic information, when the patient's eyes are open, CLF should be affected when the stimulated hand is excluded from vision, not when the responding hand is excluded from vision. In order to investigate this hypothesis, a patient with a callosal lesion was subjected to CLF with eyes closed and open. With eyes closed, the CLF score in the left-to-right direction was significantly lower than that in the right-to left direction. With eyes open, the CLF performance in the right-to-left direction was impaired when it was the responding hand to be excluded from vision, not when it was the stimulated hand to be excluded from vision. It would, therefore, appear that the patient's CLF disturbance was not due to a somesthetic transfer deficit, but to left unilateral apraxia for the right-to-left direction errors and to left tactile finger anomia for the left-to-right direction errors. PMID- 1879162 TI - Severe negative emotional reactions in intracarotid sodium amytal procedures: further evidence for hemispheric asymmetries? AB - Intracarotid sodium amytal (ISA) procedures are commonly used to determine the lateralization of language and memory functions in presurgical evaluation of epileptic patients. Besides, they provide a means for studying putative hemispheric asymmetries in the organization of emotional behavior. In this study, we report the incidence of negative emotional reactions in eighty epileptic patients undergoing ISA procedures as a part of presurgical evaluation. There were only four such reactions in a total of 159 tests (2.5%), all in right-handed patients with left cerebral dominance for language functions. In one case, emotional outbursts occurred with barbiturization of the nondominant hemisphere. This observation invalidates the hypothesis that a loss of left-hemispheric functions generally leads to negative emotional reactions due to a right hemisphere specialization for the processing of negative emotions. Rather than pointing to fixed hemispheric asymmetries, our findings suggest that severe negative emotional reactions result from a flexible cognitive evaluation of the organism's overall situation. PMID- 1879163 TI - Unilateral spatial neglect in visual and tactile modalities. AB - The purpose of this study was to investigate whether a unilateral spatial neglect phenomenon occurs in the tactile modality in the absence of visual information. Ten patients with clinically confirmed visual spatial neglect and 10 normal controls bisected lines visually, or by touch when blindfolded. In visual presentation, the rightward deviation of the subjective midline was significantly more prominent in patients with visual spatial neglect than in normal controls. However, in the tactile tasks, there was no significant difference between the patient group and controls. From these results it was concluded that visual input may play an important role in the occurrence of the unilateral spatial neglect phenomenon. PMID- 1879164 TI - Limitations of interhemispheric extracallosal transfer of visual information in callosal agenesis. AB - A 57-year-old patient with callosal but not anterior commissure agenesis was investigated with a visual interfield comparison and a naming task. Stimuli were presented tachistoscopically either bilateral-simultaneously or unilaterally in the LVF and/or RVF. The stimuli presented bilaterally differed with respect to their degree of similarity. Whereas the patient was able to detect gross differences between stimuli presented in the left and right half-field, he was impaired at discriminating similar and identical stimuli across the half-fields. Identification by naming was correct on unilateral presentation of a stimulus, while with bilateral presentation of two stimuli, errors increased considerably with the stimulus named second. The data are thought to indicate a limited capacity of the extracallosal commissures, probably the anterior, for the transfer of visual information. PMID- 1879165 TI - Suicide notes and their implications for intervention. AB - Suicide is a complicated human phenomenon. Various points of view on the study of suicide and suicidal phenomena are warranted. Suicide notes are one such approach. This paper briefly summarizes the author's research on suicide notes and draws conclusions for preventive work with highly lethal individuals. It is hoped that these implications for intervention can be useful and life-saving, although it is concluded that there is no singular universal response to suicide. PMID- 1879166 TI - Interviews with survivors of suicides: procedures and follow-up of interview subjects. AB - In a series of 104 suicides in women, 91 primary informants were interviewed face to-face. Sixty-two informants participated in a follow-up interview by phone, conducted by an independent investigator in order to determine their attitudes toward the initial interview. One third thought that the initial interview shed new light on the suicide, and two thirds considered the interview emotionally beneficial. In all, the initial interview was a positive or neutral experience for 54 informants and negative for 6. All but one of these were recognized as problematic interview subjects at the initial interview. The remaining two subjects could not be judged at the follow-up. In order to avoid negative consequences of the interviews, the investigator should adjust the procedures and provide support in the crisis reaction. PMID- 1879167 TI - The increase of suicides in psychiatric hospitals in southwestern Germany according to diagnostic subgroups. AB - In this paper, results are shown of a study on suicides committed by psychiatric inpatients in four state mental hospitals in Baden-Wurttemberg, Federal Republic of Germany during the 15 years from January 1, 1970 up to the end of 1984. There was a mean suicide rate of 195 per 100,000 admissions. A comparison of 5-year sequences showed a significant increase of so-called hospital suicides in two of the hospitals at the end of the seventies and the beginning of the eighties. A statistical analysis of a trend of increase using nonparametric methods (Spearman rho, Kendall tau) showed a significant increase in the number of suicides and suicide rates in all four hospitals. In a second step, the same statistical procedure testing for an increase in the fifteen years was used for the group of schizophrenic (N = 106) and depressed (N = 55) inpatients who committed suicide. An impressive and highly significant increase was found especially in schizophrenic male inpatients with the ICD-9 diagnosis 295.3 (paranoid schizophrenia), and within that group, in inpatients with 3 or more inpatient treatments. There was also an increase in the depressed group, especially in female depressives, but only significant at the 5% level in the trend analysis. PMID- 1879168 TI - A longitudinal follow-up study of 583 attempted suicides, based on Hungarian material. AB - The author reports on a study conducted in three county districts, the first investigation in Hungary to also entail a follow-up study. The investigation includes all cases of attempted suicide in a 10-year period. The follow-up period was 6-16 years, an average of 11.6 years. The authors points out that in Hungary, as elsewhere, persons who have already attempted suicide are at a higher risk of committing suicide later. The distribution of this risk, however, is inhomogeneous. The subpopulation of adolescents clearly differs from the other groups, and the author tries to find the causes of this fact. He examines the lives of the persons he terms "serious attempters" after their attempt, taking into account in his sample the epidemiologic-demographical characteristics of the persons, whom he categorizes as nonserious, serious, and completed suicides. PMID- 1879169 TI - Vulnerable phases in adolescence represented by means of committed suicide. AB - This study deals with suicides of children and adolescents in the region of Tyrol, Austria from 1976-1984. The upper age limit was set at 19 years. During the time period stated above, 54 suicides were registered for the relevant age group, using police records as a source of information. Special attention was paid to the distribution of age, sex and occupation, as well as to the suicide methods. As far as age distribution is concerned, a significant increase of suicides was registered at the age of 15 and again at the age of 19. According to the authors, the reason for this increase is pronounced psychosocial changes which occur especially in these age groups and weaken social integration. The various implications ensuing from the available data are discussed. PMID- 1879170 TI - The role of depressive disorder in the suicidal behavior of alcoholics. AB - In order to examine the role depressive disorders play in the genesis of suicidal behavior of alcoholics, 330 alcoholic inpatients were examined. Within the total sample, 41% had distinct suicidal tendencies, and of those, 15% had made at least one serious suicide attempt. The MADRS and MMPI scales were used to obtain objective evaluation of the depressive disorders. The subjects were classified according to DSM-R criteria. The results show that suicidal alcoholics have statistically significantly more depressive characteristics. PMID- 1879171 TI - Patients' experience of the therapeutic process in a crisis intervention unit. AB - To all patients hospitalized in 1986 in the Crisis Intervention Unit in Ljubljana, Yugoslavia, an inventory was sent. In this way, we tried to find out how the patients experience the treatment and stay on the Unit, what is most helpful in solving their problems and what are, in their opinion, the direct gains of hospitalization. On the basis of the results, we determined what should be changed or improved to make the treatment in our Unit more effective. PMID- 1879172 TI - A dermatologic diary. Portrait of a practice. PMID- 1879173 TI - Allergic cheilitis due to castor oil in lipsticks. PMID- 1879174 TI - Accidental intravascular injection during infiltration anesthesia of the skin. AB - Accidental intravascular injection of lidocaine during the induction of infiltration anesthesia for dermatologic surgery is an occasional and harmless occurrence. The author noted nine such episodes in a three-year period of full time private dermatologic practice. A very brief, sharp, stinging pain lasting only seconds and immediately followed by blanching in a vascular distribution characterized these episodes. The blanching, resulting from the 1:200,000 epinephrine solution used in the lidocaine solution usually disappeared within five to ten minutes. Patients experienced no ill effects. The standard textbooks and reviews caution practitioners to aspirate before injecting a local anesthetic; this is unnecessary when performing infiltration anesthesia of the skin. PMID- 1879175 TI - Cutaneous lesions of histoplasmosis with transepidermal elimination in a patient with acquired immunodeficiency syndrome. AB - Histoplasma capsulatum is a dimorphic pathogenic fungus that produces a variety of self-limiting disease syndromes in healthy persons, but commonly disseminates in immunocompromised hosts. Although histoplasmosis has been recently described in patients with acquired immunodeficiency syndrome, it is an uncommon finding, occurring in fewer than 0.5 percent of patients with acquired immunodeficiency syndrome. We are reporting a second case of disseminated histoplasmosis presenting as keratotic papules with transepidermal elimination of Histoplasma capsulatum. Our case demonstrates the importance of including histoplasmosis in the differential diagnosis of keratotic papules occurring in patients with acquired immunodeficiency syndrome. PMID- 1879176 TI - Squamous cell carcinoma of the scrotum. AB - A patient with psoriasis was found to have a large mass on his scrotum. He was at increased risk for the occurrence of skin cancer, both from the treatments he received for control of his psoriasis and from previous occupational exposure. We present his case and review the risk factors involved. PMID- 1879177 TI - Ichthyosiform sarcoidosis: report of a case. AB - Sarcoidosis is a systemic granulomatous disease of undetermined cause, with cutaneous manifestations occurring in up to 35 percent of patients. We report a case of the rare form of ichthyosiform sarcoidosis occurring in a young black woman. PMID- 1879178 TI - Sudden appearance of multiple keratoacanthomas three weeks after thermal burns. AB - The sudden appearance of multiple keratoacanthomas in a patient who has sustained a thermal burn is extremely uncommon. This case report describes a sixty-four year-old man who noted multiple keratoacanthomas within three weeks after being involved in a gasoline explosion. Multiple keratoacanthomas appear to be a rare complication of thermal cutaneous injury in predisposed persons. PMID- 1879179 TI - Eruptive vellus hair cysts and neurologic abnormalities: two related conditions? AB - A fifteen-year-old white boy with a history of seizure disorder, borderline cognitive function, academic difficulty, and explosive temper outbursts was evaluated for asymptomatic flesh-colored papules appearing on his chest, abdomen, and axillae. Examination of a biopsy specimen showed eruptive vellus hair cysts; results of genetic, endocrinologic, and neuropsychiatric evaluation revealed abnormalities suggestive of a previously undescribed neurocutaneous syndrome. PMID- 1879180 TI - Nonvenereal sclerosing lymphangitis of the penis. PMID- 1879181 TI - Considerations in comparing intravenous and intramuscular antibiotics. AB - With the implementation of prospective payment (e.g. diagnosis-related groups [DRGs] and cost containment efforts, physicians and pharmacists have had to reevaluate current drug delivery systems in the search for the least costly means of administering parenteral products. The following describes a three-phase approach to fully assess relative antibiotic cost and to assess economic efficiencies of intramuscular and intravenous administration of antibiotics. Relative costs of therapy consist of acquisition cost, administration cost and total cost of self-administration. Various intravenous administration systems are described, as are considerations for intramuscular administration. Comparisons are made using intravenous and intramuscular administrations of cefazolin, gentamicin, penicillin and imipenem. Using a 'best case' scenario, the intramuscular route was found to be up to one tenth the expense of the intravenous route in certain instances. Also, the intramuscular route may facilitate early discharge and self-administration in the home. Antibiotics available for intramuscular injection should therefore be considered as an economically efficient alternative to intravenous injections, in appropriate patients. PMID- 1879182 TI - Parenteral antibiotic therapy in outpatients: quality assurance and other issues in a protohospital. AB - Antibiotics can be administered parenterally to outpatients in order to achieve adequate serum levels to treat such infections as endocarditis, osteomyelitis and diabetic foot infections, and to eradicate such difficult-to-treat organisms as methicillin-resistant Staphylococcus aureus, cephalothin-resistant gram-negative bacilli and invasive fungal infections. At Intracare, a free-standing clinic for such therapy, 3,247 outpatients have been treated to date. Besides the type of infection, criteria for patient selection include improvement in the patient's condition, a desire to leave the hospital, an adequate support structure at home, patient compliance and adequate insurance coverage. The most frequently treated infections have been osteomyelitis, followed by infection of skin and skin structure. Ceftriaxone and cefazolin are the two most frequently utilized antibiotics. The program at Intracare is used to examine such issues of quality assurance as patient compliance, therapeutic outcome, adverse events and patient satisfaction in this largely unregulated multibillion dollar industry. It is likely that such infusion centers will evolve into protohospitals, day care centers for present-day medical-surgical patients not occupying intensive care beds. PMID- 1879183 TI - Imipenem/cilastatin: evolution of the sustained-release intramuscular formulation. AB - Since 1983, numerous studies have confirmed the efficacy of imipenem/cilastatin as monotherapy for polymicrobial and multiresistant infections. Doses range from 1 to 4 g/day, usually given in 3-4 intravenous infusions. Recently, a sustained release, intramuscular formulation of imipenem/cilastatin sodium has been developed. Investigations in both animals and healthy human volunteers have shown that this formulation maintains plasma concentrations of imipenem above susceptibility breakpoints for nearly twice the duration provided by similar intravenous doses. Although peak concentrations are lower with the intramuscular formulation, current research suggests that the efficacy of beta-lactam antibiotics is more closely related to the duration that levels are sustained above minimum inhibitory concentrations, rather than to the magnitude of peak concentrations over minimum inhibitory concentrations. Hence, the intramuscular formulation of imipenem/cilastatin sodium holds promise as an efficient, effective regimen in patients with serious infections of mild to moderate severity. PMID- 1879184 TI - Twice daily intramuscular imipenem/cilastatin in the treatment of skin and soft tissue infections. AB - One hundred and two patients were enrolled in an open-label evaluation of intramuscular imipenem/cilastatin using doses of either 500 or 750 mg every 12 h in the treatment of mild to moderately severe skin and soft tissue infections. Seventy-four of 102 patients were clinically evaluable. Thirty-one patients had abscesses, 20 had cellulitis and 23 had wound infections. One hundred seventy eight isolates were recovered from these 74 patients (average 2.4 isolates/patient). Sixty of 74 evaluable patients (82%) were cured; 12 of 74 (16%) were improved. Two patients failed to improve. Therapy was well tolerated. Adverse effects occurred in 8 patients. All of these effects were minor, and none required discontinuation of therapy. Eighty-two percent of patients reported no pain with injections. Therapy did not need to be interrupted or discontinued in the remaining 18% of patients reporting moderate local pain with injections. Peak and trough serum imipenem levels were measured in 15 patients receiving a 500-mg intramuscular dose of imipenem/cilastatin. The mean peak imipenem concentration in 15 patients was 10.7 micrograms/ml (range 3.3-17.8); the mean trough concentration was 2.1 micrograms/ml (range 0.8-4.9). The trough levels were higher than those found in healthy volunteers and may reflect the age and mild renal dysfunction in this group of treated patients. Imipenem/cilastatin used for mild or moderate skin and soft tissue infections was both efficacious and well tolerated. Intramuscular therapy with this agent offers advantages over intravenous therapy because of its long apparent half-life and pharmacokinetics. PMID- 1879185 TI - Intramuscular imipenem/cilastatin treatment of upper reproductive tract infection in women: efficacy and use characteristics. AB - We evaluated the efficacy, patient and medical staff acceptance, and costs of intramuscular therapy with imipenem/cilastatin for mild to moderate upper reproductive tract infection in hospitalized women in an open study. Thirty-five patients were enrolled, and 29 successfully completed the protocol. Of these, 90% were satisfactorily treated with imipenem/cilastatin given intramuscularly. Twenty-eight of 29 subjects tolerated the intramuscular injections well, although 7 women noted mild to moderate discomfort during injection. All patients who had previously received intravenous therapy (24/29) stated that they preferred the intramuscular injections to continuation or reinitiation of intravenous treatment. Therapy with intramuscular imipenem/cilastatin (assuming a marketed price per gram of approximately $30) was associated with cost savings in comparison with other regimens offering similar antibacterial coverage. Initial care provider resistance to treatment with intramuscular imipenem/cilastatin was overcome due to patient satisfaction. Intramuscularly administered imipenem/cilastatin was effective, generally well tolerated, and resulted in cost saving. Intramuscular administration of imipenem/cilastatin may be a preferred antibiotic treatment in patients with mild to moderate infection due to susceptible microorganisms. PMID- 1879186 TI - Intramuscular imipenem as adjuvant therapy for acute cholecystitis and perforated or gangrenous appendicitis. AB - An open-label prospective study was performed employing intramuscularly administered imipenem as an adjunct to surgery in 20 patients with acute cholecystitis and 24 patients with perforated or gangrenous appendicitis. Three (12.5%) septic failures occurred in appendicitis patients and 2 (10%) failures in cholecystitis patients. There were no deaths. Adverse effects were minor, and there was no toxicity. Although failures were not associated with in vitro resistance, Pseudomonas spp. were recovered from 2 of 3 appendicitis failures. Intramuscular imipenem appeared to be an effective single-drug antimicrobial when used as an adjunct to surgery in patients with acute cholecystitis or perforated appendicitis. It should be a more cost-effective alternative to the current multiple-drug therapy frequently employed in patients with intra-abdominal sepsis. PMID- 1879187 TI - Intramuscular imipenem/cilastatin in multiple-dose treatment regimens: review of the worldwide clinical experience. AB - Multicenter noncomparative trials of intramuscular administration of imipenem/cilastatin for the treatment of a variety of infections requiring multiple-dose therapy are reviewed. Fourteen centers in the United States and 18 centers elsewhere participated in these studies. A total of 686 patients (461 evaluable) were treated worldwide. The severity of the infection was rated as moderate in 58.9%, mild in 37.2% and severe in 0.6%. The most common sites of infection were the skin and soft tissue (36.2%) and intra-abdominal (17.6%). Polymicrobial infections were relatively common (27%). Dosing regimens in evaluable patients were 500 mg every 12 h (45.1%), 750 mg every 12 h (36.2%) and 500 mg every 8 h (18.6%). The overall clinical outcome was favorable (clinical cure or improvement) for 95% or more of the evaluable patients with the various body system infections, except in gynecologic infections where 89% of the evaluable patients had a favorable outcome and for sepsis where the favorable outcome was 76%. Where data were available for analysis (skin and soft tissue infections) there was no difference in favorable clinical outcome among patients with moderate infection treated with 1.0 g/day (95% favorable) compared with 1.5 g/day (94% favorable). The overall bacteriologic eradication rate was 91%. Clinical adverse effects were similar in type but less common in frequency than those noted in other studies with the intravenous formulation, with nausea, vomiting and diarrhea being most common; no instances of seizures or confusion were observed. The laboratory adverse effects were similar to those seen in other studies with the intravenous formulation, with increased liver enzyme values the most common. The intramuscular injection was well tolerated in 87% of the patients and moderately well tolerated in 6.6%. The efficacy and low incidence of side effects of the intramuscular formulation of imipenem/cilastatin are significant advantages in the cost-effective treatment of infections. PMID- 1879188 TI - Overall clinical utility of the intramuscular preparation of imipenem/cilastatin. AB - Imipenem is the broadest-spectrum antibiotic currently available but requires frequent intravenous dosing for efficacy. A recently formulated finely milled preparation can be given intramuscularly in small volumes and demonstrates kinetics favorable for 12-hourly intramuscular administration. The intramuscular imipenem formulation has been proven to be effective for mild to moderate infections of many body sites, as demonstrated by other papers in this symposium. The advantages of intramuscular administration include: less frequent dosing, avoidance of the complications of intravenous administration (phlebitis, bacteremia, fluid overload, nursing time), ability to use the drug in settings where intravenous administration is either undesirable or impossible and, surprising to medical personnel, greater patient satisfaction. PMID- 1879189 TI - Study of the identification of enterotoxigenic Escherichia coli by LT-DNA gene hybridization. AB - Reference strains of enterotoxigenic Escherichia coli (ETEC), non-ETEC, and other enteropathogenic bacteria were used to prove the reliability of LT-DNA gene hybridization. In the test, LT-DNA gene hybridization was compared with plate immunohemolytic test (PIHT) in identifying LT-ETEC. The results obtained by both methods showed no significant differences. 791 strains of E. coli isolated from 1,875 children with acute diarrhea in Taiyuan Children's Hospital were examined for LT-ETEC by LT-DNA gene hybridization and PIHT. 289 strains examined by LT-DNA gene hybridization were LT positive, while 205 strains examined by PIHT were LT positive. Three different assays were done: colony hybridization, PIHT and fecal direct blot hybridization on each of 74 fecal specimens from children with acute diarrhea. It was found that identification of LT-ETEC using fecal direct blot hybridization is a simple, sensitive and more practical method. PMID- 1879190 TI - Causes of death and long-term prognosis after myocardial infarction in patients with diabetes mellitus. AB - The long-term prognosis and causes of death of myocardial infarction (MI) in 62 diabetics were studied. The mean follow-up time was 6.2 years, 11 patients died in the acute stage of MI, 9 of them (81.8%) had anterior infarction and their major causes of death were ventricular fibrillation and cardiogenic shock (72.2%). 19 died in the follow-up period, 14 of them (73.68%) had inferior and anterior septal infarction; and most died of reinfarction and sudden death. The cumulative survival rate 1, 2 and 5 years after MI was 80.7%, 71.9% and 57.9%, respectively. The results suggest that treatment and prevention of MI in patients with diabetes be more attentive to prevent ventricular fibrillation and cardiogenic shock during the acute stage and in the later stage more attention should be paid to preventing reinfarction. At any stage of the disease, strict diabetic control is of vital importance. PMID- 1879191 TI - Case-control study on pathogenesis of pneumonia in children aged 0-2 years. AB - In order to know the incidence of risk factors predisposing children to pneumonia, case control study was carried out in six MCH Model Counties in 1986. Single factor analysis showed 29 factors were responsible for the increasing incidence of pneumonia. 13 of 29 factors were major pneumonia risk factors by the standard of means greater than 15 and OR greater than 3. They were malnutrition, anemia, riskets, pneumonia history, repeated colds, chronic diarrhoea, congenital malformation, asphyxia neonatorum, amniotic fluid aspiration, artificial feeding, too much clothing, family member with acute respiratory illness (ARI) and contact with ARI patients. Among them 7 factors were related to individual health condition. Therefore, it is important to improve general health of children so as to reduce the incidence of pneumonia. PMID- 1879192 TI - Experimental and clinical trial of albendazole in the treatment of Clonorchiasis sinensis. AB - Rats and dogs experimentally infected with Clonorchias sinensis metacercariae were treated orally with albendazole. Necropsy done seven days after treatment revealed that the worm reduction rates were 83.6% and 96.8% respectively. Clinically, 131 patients were treated with 3 different dosage regimens in 3 study groups. In patients receiving 5 mg/kg b.i.d. for 7 consecutive days, the stool egg negative conversion rates 1-month and 6-month post treatment were 90% and 92.6%, while in patients receiving 10 mg/kg b.i.d. for 7 consecutive days the rate were both 100%. In another group of patients receiving 10 mg/kg b.i.d. for 3 consecutive days, the 1-month and 3-month average stool egg conversion rates after treatment were only 40.0% and 28.3% respectively. The side reactions of albendazole were mild and transient. The liver and renal function tests, electrocardiography and blood and urine examinations showed no remarkable changes before and after treatment. The therapeutic effect of albendazole is comparable to praziquantel. It has the advantage of clearing various intestinal helminthic infections simultaneously, very low toxicity, excellent tolerance and relatively low cost, though its treatment course for clonorchiasis needs 7 days. PMID- 1879193 TI - Protein kinase C in the promyelocytic leukemia cell differentiation of granulocytes. AB - When the leukemia cells in 14 patients with acute promyelocytic leukemia (APL) were induced by all-trans retinoic acid (RA) treatment, the activity of protein kinase C (PKC) increased with the differentiation. In the control cells, the activity of PKC was only 47 +/- 39.3 pmol.mg-1/min, while it was 149.3 +/- 150.1 pmol.mg-1/min after differentiation. There were 90.1 +/- 7.2% promyelocytes in the control group, and 8.9 +/- 5.6% in the induction group. Therefore, we think that there is a close correlation between PKC and the differentiation of promyelocytic leukemia cells. PMID- 1879194 TI - Diagnostic value of quantitative mapping of atrial activation for the cardiac accessary pathway location. PMID- 1879195 TI - Relation between changes of TXB2 and PGF1 alpha and the severity of the disease and pathological lesions in cases of severe icteric hepatitis. AB - Clinically, 32 cases of intrahepatic cholestasis and 30 cases of severe chronic hepatitis with a bilirubin level higher than 171 mumol/L were studied. The results showed that bilirubin was 420 mumol/L in the first group, and 480 mumol/L in the second group (P greater than 0.05); TXB2 was 306 pg/ml and 271 pg/ml (P greater than 0.05) while PGF1 alpha was 253 pg/ml and 494 pg/ml (P less than 0.05) respectively, both were higher than their normal values (P less than 0.01). The cases were divided into acute, moderate and severe types according to their pathological lesions. Experimentally, intra- and extrahepatic cholestasis and necrotic liver tissues were induced by ANIT, ligation of common bile duct, and carbon tetrachloride respectively. Bilirubin was 629 mumol/L, 124.8 mumol/L, and lower than 17.1 mumol/L (P less than 0.01); plasma TXB2 was 634 pg/ml, 1036 pg/ml, and 239 pg/ml (P less than 0.01); PGF1 alpha was 186 pg/ml, 218 pg/ml, and 868 pg/ml (P less than 0.01) in the three groups respectively. No statistic difference was found in their TXB2 and PGF1 alpha. Our studies suggested that plasma TXB2 and PGF1 alpha in the liver was not related to the severity of liver lesions. TXB2 and PGF1 alpha are positively correlated with the increase of bilirubin while TXB2 is negatively correlated with PGF1 alpha, which might serve as an index for cholestasis, and be a cause for deepening jaundice. PMID- 1879196 TI - Duration of appearance of Vi antigen and Salmonella typhi in blood and urine of infected models. AB - Salmonella typhi (S typhi) infected models were established to evaluate the latex agglutination test (LAT) and staphylococcal coagglutination test (SCT) for the detection of S typhi Vi antigen in blood and urine. Antigens in serum or urine were detected within 7 days after infection with positive cultures, and decreased in 2 weeks. LAT and SCT were positive in 7 mice with no bacteria isolation from blood and urine but their spleen aspirates yielded S typhi. Both tests are rapid and sensitive and may be used for the diagnosis of typhoid infection, especially in partially treated patients when their blood cultures are negative. PMID- 1879197 TI - Indirect lymphography with Isovist-300 in various forms of lymphedema. AB - Twenty patients with various forms of lymphedema were studied by indirect lymphography. Isovist, a new non-ionic, water-soluble, dimeric contrast media, was used for intradermal infusion. Simultaneous indirect lymphography showed characteristic patterns of lymphatics. The initial lymphatics were visualized by intradermal infusion of the newly developed isovist. However, they were not opacified with direct lymphography unless in the presence of valvular insufficiency. No systemic side-effects were observed except for a feeling of discomfort at the injection site. The results showed that indirect lymphography with intradermal infusion of Isovist is useful for demonstrating dermal lymph vessels and for the diagnosis of lymphedema. PMID- 1879198 TI - Studies of rhinitis medicamentosa. AB - Nasal mucous membrane of patients with rhinitis medicamentosa caused by prolonged use of decongestants (privine) was studied by measurement of nasal mucus clearance time and observation of pathological changes under both optical and electron microscopes. It was found that privine destroyed the nasal cilia and mitochondria of epithelial cells, and disturbed their function so that they were damaged and dropped. Pathologically, the nasal epithelia were swollen, the arterioles dilated, and the glands proliferated. Twenty-two patients with rhinitis medicamentosa were treated by topical dexamethasone or triamcinolon in normal saline for 1-2 weeks followed by normal saline as regular nasal drops. Eight patients were treated effectively by oral ATP 20mg tid. The results were evaluated by nasal mucus clearance time measurement and rhinomanometry. PMID- 1879199 TI - Lumbar spinal synovial cysts. Review and case reports. PMID- 1879200 TI - Gynandroblastoma of the ovary. A case report. AB - An ovarian gynandroblastoma was found in a 59-year-old woman. The tumor consisting of mixed Sertoli-Leydig cells and granulosa-theca cells demonstrated no malignant features. Bisexual cells in gynandroblastoma derived from a common gonadal mesenchyme precursor or indifferent cell. The excision of appendages with tumor or hysterectomy was sufficient. PMID- 1879201 TI - Multilocular cystic renal cell carcinoma. Radiological diagnosis. AB - Multilocular cystic renal cell carcinoma (MCRCC), and its pathological characteristics and roentgenological and B-mode ultrasonographic appearances are described. MCRCC, a special renal carcinoma, can be divided into localized and diffused forms. PMID- 1879202 TI - Management of HIV disease in China. PMID- 1879203 TI - Captopril as a component of cardioplegia in protecting the myocardium from global ischemia during open heart surgery. A preliminary clinical report. AB - It was demonstrated recently that a local renin-angiotensin system (RAS) exists in the heart and coronary vessels, and the angiotensin converting enzyme inhibitors can protect the heart from ischemia. Eight patients with NYHA class II IV subjected to valve replacement were studied in protecting the heart from global ischemia with captopril during open heart surgery. After the ascending aorta was clamped, 500-1000 ml 4 degrees C modified St. Thomas No 1 cardioplegic solution containing 0.058-0.23 mmol/L captopril was perfused into coronary arteries under pressure until the electrocardiogram showed disappearance of myocardial electroactivity. The cardioplegic perfusion was repeated every 30 minutes thereafter during cardiopulmonary bypass (CPB). All the hearts rebeat after reperfusion either spontaneously or from defibrillation without any trouble. Three patients developed an A-V dissociation which returned to sinus rhythm or atrial fibrillation after a tiny dose of dopamine or isoprenaline intravenously. All the patients weaned from the CPB easily with a stable heart rate and a reasonable MAP. None of them needed inotropic support, even those with severe heart failure before operation did not either, and all recovered uneventfully. PMID- 1879204 TI - Plastic surgery in China. PMID- 1879205 TI - Myocardial infarction due to isolated left circumflex or right coronary artery occlusion. AB - The electrocardiographic (ECG) patterns related to clinical spectrum and angiographic features were assessed in 41 patients with first myocardial infarction due to isolated left circumflex coronary artery (LCX) occlusion, and compared to those in 45 patients with right coronary artery (RCA)-related infarction. The occurrence of inferior Q waves was similar in patients with LCX and RCA occlusion, but lateral Q waves and an abnormal R wave in lead V1 were more frequently seen in patients with LCX-related infarction (46% vs 7% and 51% vs 4%, respectively). Compared with patients with LCX-related infarction without an abnormal R wave in lead V1 and those with RCA occlusion, patients with LCX related infarction and an abnormal R wave in lead V1 associated with inferior and/or lateral Q waves had larger left ventricular end-diastolic and end-systolic volumes, lower ejection fraction, higher incidence of total occlusion of a dominant LCX without collaterals, and more cardiac events during follow-up. The study suggests that the presence of lateral Q waves and an abnormal R wave in lead V1 after myocardial infarction may be a useful marker of LCX occlusion, and that patients with LCX-related infarction may have different status of left ventricular function depending on the size of circulation and the status of residual flow to the infarct region during LCX occlusion. PMID- 1879206 TI - Effects of antihypertensive factor from erythrocyte of spontaneously hypertensive rats on the blood pressure and Ca2+ influx of arterial smooth muscle in rats. AB - The effects of a partially purified antihypertensive factor (AHF) from erythrocytes of spontaneously hypertensive rats (SHR) on the blood pressure (BP) and Ca2+ influx of vascular smooth muscle (VSM) in rats were studied. The results indicated that AHF could produce a marked prolonged depressor effect and significantly inhibit the Ca2+ influx dose-dependently on both SHR and renal hypertensive rat (RHR) either in acute or in chronic experiments, but not on normotensive rats. It suggested that the inhibition of Ca2+ influx might be one of the important mechanisms for AHF as an endogenous depressor substance. PMID- 1879207 TI - CT-guided stereotactic evacuation of hypertensive intracerebral hematoma. AB - From January 1986 to June 1989, the CT-guided stereotactic evacuation was performed in 38 cases of hypertensive intracerebral hematoma with satisfactory result. 24 patients were male and 14 female. The age ranged from 37 to 78 years, with an average of 55. 24 cases had their hematoma in internal capsule, 7 in cerebellum, 5 in subcortex, and 2 in brain stem. The interval between the occurrence of hemorrhage and evacuation of hematoma was 24 hours or less in 18 cases, 2-3 days in 14 and 4-7 days in 6. The volume of hematoma was estimated by CT scanning being more than 100 ml in 6 cases whereas much less in 2 cases of the brain stem. PMID- 1879208 TI - Lymphonodovenous anastomosis in the treatment of chyluria. AB - Thirty cases of chyluria were treated by means of lymphonodovenous anastomoses according to the principles of lymphovenous shunt. A conical tissue of lymph node close to the greater saphenous vein in the inguinal region was removed and the remaining tunnel-shaped node was anastomosed to the vein to drain the lymph into the venous system. Twenty-one cases were followed up for six months after the operation. Among them, 16 (76.2%) showed disappearance of chyluria, and 2 (9.5%) were improved, giving an effective rate of 85.7%. This operation avoids damage to both the afferent and efferent lymphatic vessels, and affords a large anastomotic stoma for free passage of the lymph into the vein. PMID- 1879209 TI - Anti-lipid peroxilative effect of ginsenoside Rb1 and Rg1. AB - It has been reported that Ginsenoside can increase body resistance to many harmful factors and protect tissues from damage when an organism is in stress. To understand the mechanism of this action, a study on the antioxidative effect of Ginsenoside Rb1 and Rg1 was carried out. Results showed that Ginsenoside Rb1 and Rg1 could inhibit lipid peroxidation of rat liver and brain microsomes and that Rb1, at the final concentration of 10(-4)-10(-3) mol/L, could scavenge O2-. induced by liver microsome-NADPH-gossypol system. In in vivo experiment, Rb1, at a dose of 50 and 25 mg/kg/day x 3 ip, inhibited MDA formation in liver homogenate of rats by 26.8% (P less than 0.05) and increased the activities of catalase and GSH peroxidase by 47.2% (P less than 0.001) and 96.4% (P less than 0.001), respectively. However, no change in the activity of superoxide dismutase was found in liver cytosol of rats treated with Rb1. PMID- 1879210 TI - Effect of ginsenopolypeptide on the 3H-TdR integration of human blood lymphocyte. AB - This paper reports the study of the effect of ginsenopolypeptide on 3H-TdR integration in normal human blood lymphocytes in vitro with micro-blood culture method of 3H-TdR integration. The results showed that the effect of ginsenopolypeptide on 3H-TdR integration in normal human peripheral blood lymphocytes which can be activated by phytoagglutinin was enhanced at low dosage and inhibited at high dosage, and its stimulating spike was 10(-6) micrograms/ml (P less than 0.01). PMID- 1879211 TI - Magnetic transcranial motor and somatosensory evoked potentials in cervical spondylitic myelopathy. AB - Fourteen cervical spondylitic myelopathy (CSM) patients were clinically diagnosed and proved by MRI and surgery. The results of 11 patients showed that 8 (72.7%) had motor evoked potential (MEP) abnormality with prolongation of central motor conduction time (CMCT) in 7, and absence of motor action potentials after C7 stimulation in one. Five of the 11 patients showed normal somatosensory evoked potentials (SEPs) along the same arm. The short term (2-4 weeks) follow-up study in 10 patients showed normalization of the prolonged CMCT in one and reappearance of MEPs with C7 stimulation in another. Non-invasive and painless magnetic transcranial stimulation of the motor pathways is useful in the assessment and management of CSM patients, and is better than electrical stimulation. PMID- 1879212 TI - Cepholosporium acremonium. A new strain of fungus causing white piedra. AB - A strain of fungus (CZ408) was isolated from white piedra of a female child. Mycological identification showed that it is the first case in the world. Asymptomatic white nodules were noted on the hair of the scalp, and they were distributed irregularly along the shaft 4-10 cm from the scalp. The nodules, hard, not easily broken or removed, consist of hyphae, spores and metabolic materials around the hair. Oral antimycotic drugs are effective in treating this disease. PMID- 1879213 TI - Hypothalamic encephalitis with oligodendrocytic glial nodules. Case report of a Chinese boy. AB - A case of hypothalamic encephalitis proved by postmortem examination is reported. The patient was a three-year-old Chinese boy who had complained of obesity for one year and fever for half a year. Three days after admission to a hospital, the patient suddenly died of allergic reaction to intramuscular penicillin, without additional complaints. Autopsy revealed severe bilateral outfall of neurons in the ventromedian hypothalamic nuclei with diffuse hyperplasia of astrocytes and some glial nodules consisting chiefly of oligodendroglias and perivascular cuffing. Similar changes were noticed in hypothalamus at the level of optic chiasm, but the posterior hypothalamic nuclei and lateral hypothalamic nuclei were intact. This article provides significant data for the study of hypothalamic function. PMID- 1879214 TI - Treatment of cleft lip and cleft palate. AB - The first case of cheiloplasty recorded was in China at about 200 BC. The technique of course has been vastly improved over the centuries. Cleft lip and/or cleft palate are among the most common congenital anomalies in China and the world. There is controversy over some of the surgical techniques used and age for operation, especially in cleft palate, but the condition requires surgery. Unilateral cleft lip is operated on at 3-6 month of age and bilateral cleft lip at 6-12 month of age. Views on palatoplasty are: 1. Cleft palate should be repaired at an early age; 2. Supplementary orthodontic treatment to expand the upper arch postoperatively is necessary, and orthognathic surgery is performed if needed when the patient has matured. This is the best choice at present. PMID- 1879215 TI - Monitoring of filarial antigens in jirds and patients after treatment. AB - We developed a sandwich ELISA with monoclonal antibodies to monitor filarial antigens in animals and patients after infection and treatment. Levels of antimicrofilarial antibodies and parasite antigens were measured periodically in 40 B. malayi infected jirds. In all animals L3 HC11 antigen was detected earlier than Mf ES34 antigen, while antimicrofilarial antibodies appeared much more slowly. These serologic changes precede the onset of patent infections. After 3 courses of treatment with DEC and M170, the levels of parasite antigen in sera and of Mf in peritoneal cavities were monitored in 23 infected jirds. In 8 jirds Mf became negative, no adult worms were found in 7 jirds and a single degenerating female worm was present in 1 jird. ES34 and HC11 were undetectable in 8/8 and 6/8 necropsy sera. Mf persisted in 11 animals, 9 jirds were necropsied, 8 contained adult worms. Detectable levels of ES34 or HC11 antigen were present in 7/9 and 8/9 from these animals. In sham-treatment, few changes were noted in control animals. Thus, parasitological findings at necropsy are correlated with the results of antigen detection assay. We analyzed serial serum samples from 32 bancroftian microfilaremia collected 1-42 months after DEC therapy. Mf resolved rapidly in all treated individuals. ES34 disappeared faster than HC11, 3 months after treatment. Levels of ES34 and HC11 antigens remained detectable or rising after treatment in 8 and 10 individuals. Four patients' Mf recurred 20-42 months after treatment. These findings show that the remaining or a rise in serum levels of antigen after therapy predicts recurrent microfilaremia in patients and additional treatment is needed. PMID- 1879216 TI - Adrenal autotransplantation with A-V anastomosis for treatment of Cushing's disease. A follow-up study of 31 cases. AB - Thirty-one patients with Cushing's disease were treated with bilateral adrenalectomy and partial left adrenal autotransplantation with A-V anastomosis. They were followed up for 1 to 5 years. Three patients failed after adrenal autotransplantation to the abdominal muscle with the left gland's central vein anastomosed to the inferior epigastric artery. Twenty-eight patients underwent adrenal autotransplantation to the omentum with the gland's vein anastomosed to the gastroepiploic artery. Steroid could be omitted a short period after operation and life-long replacement therapy was avoidable in most patients. A few patients subsequently developed hypocorticalism. Two died and one had recurrence of Cushing's disease. Clinical and animal experimental results showed that the omentum is suitable for adrenal autotransplantation with A-V anastomosis. Transabdominal bilateral adrenalectomy and adrenal autotransplantation to the omentum with A-V anastomosis are acceptable in the treatment of Cushing's disease. The subsequent development of hypocorticalism and recurrence of Cushing's syndrome are also discussed. PMID- 1879217 TI - Suppressive effect of high energy shock waves on tumor cells. AB - Suppressive effect on tumor cells of high energy shock waves (HESW) has aroused the interest of physicians in recent years. We assessed experimentally the cytotoxic effects of HESW on tumor cells both in vitro and in vivo and determined whether a Chinese domestic lithotriptor is capable of generating effective HESW, which has the potential to break tumor cells, reduce cell viability, retard cell growth, delay doubling time, impair cell attachment and cell clonogenicity. In nude rats, HESW was able to delay tumor growth and reduce tumor size without evidence of metastasis. The nature of HESW in the induction of cell damage and its clinical application need to be further investigated. PMID- 1879218 TI - The use of corticotropin releasing factor (CRE) for the treatment of post operative cerebral edema. A preliminary study. AB - Synthetic corticotropin-releasing factor (CRF) was administered pre-operatively to five patients who underwent craniotomy for brain tumors, acute subdural and intracerebral hematomas. After craniotomy, an intraventricular catheter is placed in the ventricle, on the normal side of brain. This is for intracranial pressure monitoring. The data obtained were pooled and compared with the saline group (n = 6). The CRF group was found to have statistically significant difference (P less than 0.01). This preliminary study showed that CRF decreases postoperative edema. PMID- 1879219 TI - Verapamil and ventricular tachycardias. AB - In the absence of myocardial ischaemia, ventricular tachycardias occurring in patients with structural heart disease rarely respond to calcium antagonists like verapamil. In contrast, verapamil is markedly effective in the acute management of "supraventricular" tachycardias. Thus, intravenous verapamil has often been used for therapeutic and diagnostic purposes in patients with wide QRS complex tachycardias. This report details two unusual cases of ventricular tachycardia that are verapamil-sensitive. They highlight two major categories of "idiopathic" ventricular tachycardia, namely fascicular tachycardia and catecholamine-mediated ventricular tachycardia. The risks of verapamil administration for wide complex tachycardias are also reviewed. PMID- 1879220 TI - Changes of negative charge on RBC and glomeruli and its relation to the proteinuria of adriamycin nephrosis in rats. AB - The depth and area-percentage of Alcian blue (AB) staining of glomeruli, the ability of RBC to bind AB and the onset of proteinuria in adriamycin nephrosis in rats were studied. The results showed that the negative charge (NC) on RBC and glomeruli decreased significantly after injection of adriamycin and there was a positive correlation between them (r = 0.77, P less than 0.01). There was a negative correlation between the amount of NC on the RBC and the amount of urinary protein (r = -0.5231, P less than 0.01), and also between the amount of NC on the glomeruli and the amount of urinary protein (r = -0.5140, P less than 0.05). PMID- 1879221 TI - Clinical features and comprehensive treatment of late stage radiation skin injuries. AB - 105 patients with late stage radiation skin injury were treated from 1970 to 1986, using drugs combined with surgical intervention according to the clinical features of the injury. Drug therapy consisted of topical application of urea, antibiotics, trypsin and elastase, and systematic use of alpha 2-Macroglobulin. Of 62 patients receiving medication, 55 (88.7%) were completely or basically treated and 7 failed. Of 51 lesions of 43 patients receiving surgical treatment, 47 healed by first intention. In 4 patients, necrosis of partial and/or peripheral skin flaps healed after renewed repair. PMID- 1879222 TI - Study on methicillin-resistant Staphylococcus aureus in China. PMID- 1879223 TI - Pure sensory stroke confirmed by CT scan. AB - Five cases of pure sensory stroke, including two cases of cheiro oral syndrome, are reported. Of the 5 cases, 2 presented thalamic lacunar infarcts, 2 basal ganglia hemorrhages, and 1 dorsal midbrain hemorrhage on computed tomography scan. PMID- 1879224 TI - Re-appraisal of treatment of congestive heart failure. PMID- 1879225 TI - [Ultrastructural changes in joint capsule in TMJ disturbance syndrome]. AB - The joint capsule is one of component parts of joint. In order to clear the changes of the capsule in TMJ disturbance syndrome, we studied 3 normal capsules and 7 patient's capsules by light microscope and electron microscope. The results are: under LM, some fibrous materials are found on the surfaces of synovial membranes in TMJ disturbance syndrome. The synovial membranes in disease become thicker than usual. The connective tissue shows hyaline degeneration. Under EM, the surfaces of synovial membranes are covered by an irregular granulated or filamentous substance. Collagens are denatured or dissolved. Among fibrils amorphous moderate-electron dense materials are present. The authors think that these changes are associated with the autoimmune reaction in TMJ disturbance syndrome and increase the destruction of TMJ in this disease. PMID- 1879226 TI - [Primary study of condylo-pterygomaxillo-oblique projection in CT and magnetic resonance images]. AB - The literature is reviewed that we have not yet seen in the TMJ examination by X ray, CT and MR associated with the study of lateral pterygoid muscle simultaneously. In this paper we observed the CT and MR images of condylo-pterygo maxillo-oblique projection (the origin and insertion plane of the lateral pterygoid muscle), In which we can see the relationship between TMJ structures and lateral pterygoid muscle under different functional states clearly. All of the X-ray, CT and MR images were compared with each other for clinical reference. PMID- 1879227 TI - [Treatment of cross-bite of anterior teeth with rare earth magnetic appliance with double rails]. AB - In this paper, the rare earth magnets (Nd-Fe-B) were used for treatment of cross bite of anterior teeth. Eight patients were selected. In an attempt to achieve the labial movement of upper anterior teeth, removable appliance with repelling magnetic force were used. The treatment results are satisfactory. The following facts were discussed: (1) the direction of the repelling magnetic force can be controlled well with the double rails; (2) the time for treatment was short and there was no manifestation of unfavorable reaction and (3) no adverse bioeffects have been reported in regard to the use of this kind of device. PMID- 1879228 TI - [Measurement of blood flow in labial and palatal mucoperiosteal flap after sectioning the greater palatine arteries and with a labial mucosal arcuate incision]. AB - This article describes a study of determining blood flow of labial and palatal mucoperiosteal flap with radionuclide Xe-133 clearance technique before and after anterior maxillary osteotomies. The main purpose of the study was to investigate the dynamic change of blood flow. The greater palatine arteries were ligated. The studies show that compensative increasing of the blood flow of labial pedicle is seen after the operation, and that decreasing of the blood flow of palatal mucoperiosteal flap is temporary. It is suggested that the section of the greater palatine arteries is feasible. Xe-133 clearance technique is easy to operate and sensitive. PMID- 1879229 TI - [Cephalometric study of normal occlusion for functional appliance therapy]. AB - Lateral cephalograms of 140 growing subjects with normal occlusion from Beijing were computerized and analyzed. Cephalometric standards of three occlusion developmental stages, Hellman's IIA, IIIB and IVA, were obtained and evaluated in three groups as facial skeleton, jaw bases and dentoalveolar relationship, which are specifically useful for diagnosis and treatment planning with functional appliances. PMID- 1879230 TI - [Treatment of tooth sensitivity by Nd-YAG laser]. PMID- 1879231 TI - [Ultrastructural study of adenolymphoma]. AB - Ultrastructure of 10 adenolymphomas of parotid gland were studied. The neoplastic epithelium consists of "oncocytes" which are arranged in pseudostratified pattern. Their cytoplasm is almost totally packed with a large numbers of hypertrophic mitochondria showing a variety of peculiar forms. The amount and alteration of the mitochondria gradually increase in the order of pyramidal cell, common columnar cell and degenerated columnar cell. This might be a process of transposition representing degeneration due to metabolic disorder in the tumor. The obvious alterations of mitochondria are found in the cases with not only "hot" nodule but also "cold" nodule shown in the studies of 99mTc scintigraphy. There seems no relationship between "hot" nodule and alteration of mitochondria. PMID- 1879232 TI - [Replantation of frozen and boiled autogenous mandible]. AB - Mandibles devitalized by freezing or boiling after being removed from animals were reimplanted to evaluate their potentials of reunion and growth with X-ray and histological methods. The results suggested that the osteo-induction may play a partial role in the bone healing of frozen bone graft besides "creeping substitution", while the boiled one only provided a scaffold into and around which bone formation can occur. According to the rate and degree of bone graft repair, the frozen was better than the boiled which was resorbed and replaced at a slower rate. PMID- 1879233 TI - [In vitro test of influence of catechin in tea to the growth, acid production and adhesion of streptococci mutans]. PMID- 1879235 TI - [The polymerization shrinkage of light cure composite resin]. AB - The polymerization shrinkage of a number of commercially available composite resin (Starfiil, Durafill, VLC-1 and GD) and an experimental composite #1 which contains 16% DMSOC (a new monomer which expands on polymerization) has been determined using a water-filled dialometer. The results indicated that GD displayed the largest shrinkage value at 2.62 +/- 0.20%, while VLC-1, Durafill and Staifill had smaller values at 2.10 +/- 0.10%, 1.84 +/- 0.20% and 1.42 +/- 0.16%, respectively. The experimental composite. #1 underwent least contraction during setting (0.14 +/- 0.13%). The polymerization shrinkage was influenced by the filler loading and the duration of the exposure to the activating light source. There was little influence of shade of materials on the polymerization shrinkage for VLC-1. PMID- 1879234 TI - [Studies on microleakage of three kinds of dental restorative materials]. AB - In this article we studied the microleakage of three kinds of dental restorative materials by using 131I label compounds and 3H label compounds. The results revealed that the radioactive isotope reverse diffusion method has the advantages of which it is quantitative and sensitive. It is an acceptable and feasible measuring method. Under the condition described in this article, microleakage phenomenon exists in all the test materials and the margin sealing ability of EB composite resins is superior to the others. PMID- 1879236 TI - [Histologic observation of upper central incisors after surgical immediate torsion]. AB - The purpose of this study is to verify the treatment results of rotated teeth by using surgical immediate torsion method. Seven upper central incisors in four monkeys were chosen in our experiment. The surgical treatment was accomplished by rotating the teeth in about 45 degree. The animals were sacrificed at 2, 3, 4 and 12 weeks after operation. The results showed that two of seven dental pulps were necrosis, three were injured and two were normal. Absorption of dental cementum and dentine occurred at the apex and the middle third of the root. There was no evidence of ankylosis between the tooth and bone tissues. According to our experiment, we think that the surgical immediate torsion method for treating rotated teeth is not available. PMID- 1879237 TI - [The x-ray examination of periodontium]. PMID- 1879238 TI - [Clinical diagnosis of aplastic anemia]. AB - A study on the clinical diagnosis of aplastic anemia (AA) was carried out by using 5 different laboratory techniques including bone marrow aspiration and smear. Diagnosis of AA was established in 238 patients. Results with different methods were listed below: (1) Typical picture of AA was found in bone marrow smear of 196 patients. The positive rate was 82.4%. (2) Evaluation of marrow speckles might raise the positive rate to 89.9%. (3) Diagnosis of AA in 103 out of 110 patients was confirmed with bone marrow biopsy. The positive rate was 93.6%. (4) Typical 3-dimensional marrow tissue structure of AA was found in 68 out of 72 patients under scanning electron microscope, with a positive rate of 94.4%. (5) Total body bone marrow gamma-scintigraphy was performed in 56 patients; diagnosis of AA was reconfirmed in 54 patients with a positive rate of 96.4%. (6) 4 or 5 diagnostic techniques were used simultaneously in 30 patients with a positive diagnostic rate of 100%. The methodology of different techniques of bone marrow examination, the typical picture of AA and the causes of missing diagnosis were discussed with certain recommendations on each technique. PMID- 1879239 TI - [Clinical study of 63 patients with aplastic anemia by using in vitro culture of BFU-E, CFU-E, CFU-GM and of the relation between pathogenesis and treatment]. AB - 63 patients with aplastic anemia were studied by using in vitro assay for committed erythroid and granulomonocytic progenitors from the bone marrow. The T cell-mediated effects of suppression of normal hematopoiesis were observed by PBMNC of the patients when cocultured with normal bone marrow. The stimulated effects of androgen on BFU-E and CFU-E with methyl testosterone were also studied. The results showed that the PBMNC of 44.4% of the 63 patients suppressed normal hematopoiesis. 41.3% of the patients responded to methyl testosterone (MT) and 14.3% of the patients had very obvious decrease or absence of BFU-E, CFU-E and CFU-GM without evidence of immunological effects or response to androgen. According to these findings, it may be useful for clinicians to choose better therapeutic regimens for aplastic anemia. Such as BMT for the patients with hematopoietic stem cells deficiency; immuno-suppression treatment or splenectomy may be of benefit for those who suffered from immune mediated aplastic anemia (IMAA) and androstenones chosen for those sensitive to MT in vitro. There were 15 patients with IMAA treated with immuno-suppressive agents and 19 patients sensitive to MT treated with androgens. All of them had satisfactory results. PMID- 1879240 TI - [Clinical features of paroxysmal nocturnal hemoglobinuria (PNH) in China as compared with those in United Kingdom]. AB - The clinical features of 26 patients of PNH in Sheffield Blood Centre, UK and 50 cases in our hospital, observed in the same period, were compared. Each case was analysed according to the same criteria, and then comparison was made between the two groups. Results showed that in our group: male patients were more common; patients usually had mild or moderate bleeding tendency; the appearance of hemoglobinuria was delayed; abdominal pain was mostly related to hemoglobinuria but not thrombosis; pancytopenia was encountered more frequently and leucopenia as well as thrombocytopenia more remarkable; the incidence of thrombosis was not rare, but occurred rather late: thrombosis was mainly seen in superficial veins, but not veins of viscera; the major cause of death was not thromboembolism but infection. About 25% of the patients achieved long term clinical remission in both groups. None of the patients in these two series transformed to myeloproliferative disorders including acute leukemia. PNH can be considered a benign and chronic hematologic disease. PMID- 1879241 TI - [Investigation of the relation of impedance rheopneumogram with pulmonary hemodynamics and right ventricular function in patients with chronic obstructive pulmonary disease]. AB - In order to investigate the relation of impedance rheopneumogram with pulmonary hemodynamics and right ventricular function in patients with chronic obstructive pulmonary disease (COPD), we measured impedance rheopneumogram and did right heart catheterization in 150 COPD patients simultaneously both at rest and after exercise. The results showed that impedance rheopneumogram was mainly influenced by right ventricular after-load, while the influences of right ventricular pre load, right ventricular contraction, right ventricular stroke work index and cardiac output were rather small, suggesting that in COPD patients impedance rheopneumogram is valuable in predicting pulmonary arterial pressure noninvasively, but not so use in judging the right ventricular function. PMID- 1879242 TI - [Determination of the rate of micronucleus formation in lymphocytes in liver diseases and its clinical significance]. AB - The rate of micronucleus formation in lymphocytes was determined in 42 patients (including 10 acute icteric hepatitis B, 15 chronic active hepatitis B (CAH), 8 liver cirrhosis and 9 liver cancer) and 13 normal subjects. The results showed that the rate of micronucleus formation in lymphocytes in the patients with CAH (12.267 +/- 5.298%), liver cirrhosis (12.375 +/- 8.551%) or liver cancer (19.444 +/- 13.324%) was markedly higher than that in those with acute icteric hepatitis B (5.400 +/- 1.430%) or normal subjects (3.308 +/- 1.284%) (P less than 0.01). The rate of micronucleus formation in lymphocytes is higher in the liver cancer group than that in the CAH group or cirrhosis group (P less than 0.05). The rate of presence of two or more micronuclei in the lymphocytes was obviously higher in the liver cancer group (3.667 +/- 4.743%) than that in the liver cirrhosis group (1.500 +/- 1.690%), CAH group (1.467 +/- 1.807%), acute icteric hepatitis B group (0.600 +/- 1.075%) or healthy group (0.462 +/- 0.660%) (P less than 0.01 or less than 0.05). This method is much simpler than the measurement of chromosomal damage, and its reliability is as good as the latter. Measurement of micronuclei in lymphocytes can reflect the degree of liver damage in patients with the infection of hepatitis B virus. It may be used as the subclinical marker of the patients with liver cancer too. PMID- 1879243 TI - [Changes in levels of leucocytic estrogen receptor in patients with menopausal type II diabetes and its significance]. AB - The number of estrogen receptors (ER) in human peripheral leucocytes in 12 women with menopausal type II diabetes was measured with radio-ligand binding method. The results were compared with those of 12 menopausal women without diabetes and 12 normal women of childbearing age. It was found that the number of ER in the patients was significantly decreased. Our data indicate that decrease of ER level in leukocytes may be related to the pathogenesis of type II diabetes in menopausal period. PMID- 1879244 TI - [Current status of the drug therapy of sever aplastic anemia]. PMID- 1879245 TI - [The nervous system involvement in Lyme disease]. PMID- 1879246 TI - Does prophylactic use of bovine surfactant change drug utilization in very premature infants during neonatal period? AB - The efficacy of a bovine surfactant preparation (SF-RI 1) to increase survival without bronchopulmonary dysplasia (BPD) was studied in very premature infants in a multicenter, randomized sequential trial. Thirty-four infants were randomized to surfactant treatment, whereas 35 infants served as controls. As part of the study, pharmacotherapy with antibiotics, sedatives, catecholamines, diuretics, methylxanthines, mucolytics, muscle relaxants, digoxin, and indomethacin was registered during week 1 and weeks 2-4. As to the endpoint of the study a significantly increased survival rate without BPD was observed in surfactant treated infants (76%) compared to controls (40%). Significant differences concerning drug utilization were found through week 1 with increased use of methylxanthines in surfactant-treated infants, which persisted during weeks 2-4 as well as a reduced incidence of diuretic therapy in surfactant-treated infants during weeks 2-4. These differences may be attributed to the shorter interval of mechanical ventilation in surfactant-treated infants (11 days) compared to controls (27 days), and to the above mentioned increased survival rate without BPD. PMID- 1879247 TI - Absorption of intramuscular vitamin E in premature babies. Italian Collaborative Group on Preterm Delivery. AB - Vitamin E (alpha-toxopherol) is widely used, at different dosages and schedules and in different formulations, in neonatal intensive care units to prevent intraventricular hemorrhage, retrolental fibroplasia, bronchopulmonary dysplasia and hemolytic anemia of preterm infants. As part of a wider project to assess the effect of vitamin E, the present study was designed to determine whether the only intramuscular formulation available today in Italy and in other European countries (olive oil solution), and widely used in all Italian neonatal intensive care units according to a standard schedule, achieves and maintains suggested therapeutic levels, compared to the colloidal aqueous solution used in clinical trials in England and Canada, which contained the acetate ester of alpha tocopherol and as used in the USA, which contained the free tocopherol, but is not yet available in Italy. Forty-four babies, of less than 32 weeks' gestation, 670-1,800 g birth weight, were randomly allocated to one of the two formulations. We gave 20 mg/kg of vitamin E intramuscularly on 3 consecutive days starting within 8 h of birth (day 0), 24 and 48 h later (days 1 and 2). Blood, plasma, red blood cells after transfusions and milk were sampled up to the sixth day of life. Clinical data were collected up to discharge from the neonatal intensive care unit. Plasma concentrations of vitamin E (free tocopherol) averaged 1.1 at 24 h and 3.3 mg/dl at 72 h after the colloidal aqueous solution, and were about 6 times lower after the oil solution. Plasma vitamin E levels did not rise above baseline after injection of the olive oil preparation. The acetate ester of vitamin E was measured only after use of the colloidal aqueous preparation, and the highest plasma concentration averaged 1.01 mg/dl 72 h after injection. These findings have far-reaching implications related to the current clinical practice in Italy of prophylaxis with intramuscular vitamin E, using the scantily bioavailable olive oil formulation currently on the market. PMID- 1879248 TI - Human fetal tracheal smooth muscle produces spontaneous electromechanical oscillations that are Ca2+ dependent and cholinergically potentiated. AB - Although the electromechanical properties of, and the cholinergic innervation to adult airway smooth muscle has been extensively studied, the little information is available on developing human airway smooth muscle, and the role of cholinergic mechanisms in regulating bronchomotor tone. A total of 7 tracheae obtained at the time of elective abortion and between 12-16 weeks of gestational development were used in this study. For each trachea, muscle tension and transmembrane potentials were measured simultaneously using an isometric force transducer and a standard 3-M KCl-filled glass microelectrode. All preparations showed spontaneous electrical oscillations approximately 8 mV in amplitude, which could be increased using electrical field stimulation, or exogenously applied acetylcholine. This was accompanied by a corresponding increase in muscle tension. Atropine (0.1 microM) abolished this potentiation, but had no apparent effect on the oscillations. Slow-wave activity was completely suppressed in the absence of extracellular Ca2+, or in the presence of verapamil (1 microM) or quinidine (1 microM). It appears that these oscillations of membrane potential may be potentiated by cholinergic mechanisms which regulate cell membrane ion channels, thus serving to change excitability in a rhythmic manner. PMID- 1879249 TI - Suction blisters technique in amikacin diffusion through interstitial fluid in cystic fibrosis. AB - Modifications in the pharmacokinetics of aminoglycosides have been reported among patients with cystic fibrosis. We obtained suction blister fluid (SBF) to study the tissue diffusion of amikacin in cystic fibrosis in 2 children (a 9-year-old boy and a 7-year-old girl) over the course of bronchopulmonary infection. Amikacin was administered intravenously using a single dose of 5 mg/kg. The peak plasma concentrations were 24.5 and 11.2 mg/l, and the peak SBF concentrations were 8.3 and 3.2 mg/l. The ratio of the area under the curve in SBF and plasma was 58 and 60%, respectively. These results suggest a good penetration of amikacin through SBF and a good tissue diffusion of amikacin. The preliminary data suggest that the suction blister method may be useful to assess the tissue diffusion of drugs. PMID- 1879250 TI - Binding of furosemide to albumin isolated from human fetal and adult serum. AB - Albumin was isolated from pooled fetal serum from 58 placentas obtained at normal delivery at term and from pooled adult plasma from 8 individuals. Albumin isolation was carried out by means of PEG precipitation followed by ion-exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The electrophoresis on SDS-polyacrylamide gels showed only one spot that comigrated with commercial human albumin. Binding to albumin was measured by equilibrium dialysis of an aliquot of albumin solution (0.7 ml) against the same volume of 0.13 M sodium orthophosphate buffer (pH 7.4). At a total concentration of 2 micrograms/ml (therapeutic range), the unbound fraction of furosemide was 2.71% (fetal albumin) and 2.51% (adult albumin). Two classes of binding sites for furosemide were observed in fetal and adult albumin. The number of binding sites (moles of furosemide per mole of albumin) was 1.22 (fetal albumin) and 1.58 (adult albumin) for the high-affinity site and 2.97 (fetal albumin) and 3.25 (adult albumin) for the low-affinity site. The association constants (M-1) were 3.1 X 10(4) (fetal albumin) and 2.6 X 10(4) (adult albumin) for the high-affinity set of sites and 0.83 X 10(4) (fetal albumin) and 1.0 X 10(4) (adult albumin) low affinity site. The displacement of furosemide from albumin was studied with therapeutic concentrations of several drugs. Valproic acid, salicylic acid, azapropazone and tolbutamide had the highest displacing effects which were significantly higher with fetal than with adult albumin. PMID- 1879251 TI - Pharmacokinetics and pharmacodynamics of morphine in infant monkeys. AB - We report the pharmacokinetics of morphine administered as intravenous boluses in newborn (less than 7 days) and 3- to 4-month-old macaque monkeys. Morphine was administered in a series of bolus doses until PaCO2 was elevated greater than 50 mm Hg. In newborns less than 7 days of age, a mean dose of 1.4 mg/kg was required (range 0.75-2.8 mg/kg), and in the 3-month-olds, a mean dose of 1.88 mg/kg was required (range 1.5-2.5 mg/kg). The respiratory effects measured by PaCO2 and respiratory rate did not correlate with declining serum or cerebrospinal fluid morphine levels. Both newborn and 3- to 4-month-old macaque monkeys show only mild respiratory depression after intravenous morphine, at serum concentrations as high as 300-400 ng/ml. Infant and young macaque monkeys appear to be less sensitive to the respiratory depressant effect of morphine than humans. PMID- 1879252 TI - Effect of ethanol on 15-hydroxyprostaglandin dehydrogenase activity in the brain stem of the near-term fetal sheep. AB - The effect of in vitro incubation with ethanol (10-80 mM) on 15 hydroxyprostaglandin dehydrogenase (15-OH-PGDH) activity was determined in the brain stem (pons and medulla) of the fetal sheep at a mean gestational age of 126 days (term: about 147 days). Enzyme activity was determined by measuring the rate of oxidation of PGE2 to 15-keto-PGE2 using a radiometric assay. There was no statistically significant ethanol-induced inhibition of 15-OH-PGDH activity. The data apparently do not support the hypothesis that acute in vitro exposure to ethanol directly inhibits 15-OH-PGDH activity in the near-term fetal brain stem. PMID- 1879253 TI - Alfentanil pharmacokinetics in piglets with increased intra-abdominal pressure. AB - Increased intra-abdominal pressure (IAP) occurs in pediatric patients with end stage liver disease and ascites, as well as in children following surgery for diaphragmatic hernia, omphalocele, gastroschisis and orthotopic liver transplantation. Although the hemodynamic response to increased IAP is well described, little information is available regarding the effects of IAP on drug distribution and elimination. We studied the effects of increased IAP (20 mm Hg) on the pharmacokinetics of alfentanil in piglets and compared these findings with those in control animals. Increased IAP appears to have no significant effect on the volume of distribution (0.46 +/- 0.06 vs. 0.61 +/- 0.23 liter/kg), mean residence time (68.8 +/- 27.8 vs. 62.3 +/- 27.8 min) and elimination half-life (47.7 +/- 19.0 vs. 43.2 +/- 19.3 min). PMID- 1879254 TI - Effect of a traditional Chinese medicine, yin zhi huang, on bilirubin clearance and conjugation. AB - Oral administration of Yin Zhi Huang (YZH) daily for 3 days in rabbits accelerated plasma clearance of infused unconjugated bilirubin. A similar but less dramatic effect resulted from 3 days pretreatment with phenobarbital, 70 mg/kg/day orally. Similar doses were injected intraperitoneally in rats for 3 days, following which the bile ducts were ligated and bilirubin infused intravenously. Plasma clearance of unconjugated bilirubin and plasma appearance of conjugated bilirubin were faster, and hepatic bilirubin content was higher in both YZH- and phenobarbital-treated rats than in control animals. These observations indicate that YZH is as effective as phenobarbital in stimulating bilirubin metabolic pathways and suggest that the drugs may share common mechanisms of action. PMID- 1879256 TI - Communication and cytopathology--Part II: Malpractice. PMID- 1879255 TI - Probenecid pharmacokinetics in cystic fibrosis. AB - Probenecid pharmacokinetics were studied in 5 cystic fibrosis (CF) subjects and 5 control subjects at oral dosages of 5, 15, and 30 mg/kg. Serum and urine samples were collected for 8 h after administration and assayed by reverse phase high performance liquid chromatography. Pharmacokinetic parameters were estimated by model-independent methods. All parameters were compared by 2-tailed analysis of variance with two major groupings: patient and dose. Both CF subjects and controls demonstrated dose-dependent kinetics, i.e., decreased elimination constant and decreased total body clearance with increasing dosage. The volume of distribution and time to peak were the only parameters that were not significantly dose dependent. At all dosages studied, we found no significant difference in total body clearance by CF subjects. Urinary recovery in an 8-hour period was not significantly different between CF subjects and controls nor was the percentage of dose recovered in the urine at each dosage level. Time to peak concentration varied widely between 0.5 and 4 h in both CF subjects and controls. We conclude, that CF patients have normal probenecid clearance, and that the standard dose for a CF patient is sufficient to attain a serum area under the curve equivalent to that of controls. PMID- 1879257 TI - Cytomorphologic features of sputum samples from marijuana smokers. AB - Histopathologic evidence in recent literature suggests that habitual, heavy marijuana smoking causes changes in the bronchial airways similar to changes seen in older, habitual cigarette smokers. The cytologic effects of marijuana smoking on the bronchial airways were investigated utilizing a quantitative analysis of sputum. Levels of macrophages (pigmented and nonpigmented), neutrophils, mucus, mucous spirals, and columnar and benign metaplastic cells were measured. The presence or absence of dysplasia, "purse" cells, eosinophils, reactive bronchial lining cells, and benign bronchial hyperplasia was noted. Results were compared across three groups of 25 subjects each: never cigarette or marijuana smokers: marijuana only smokers: and in cigarette only smokers. Results indicate that cytomorphologic changes observed in habitual marijuana smokers are similar to changes observed in tobacco smokers and much different than those observed in nonsmokers. These cytologic findings are similar to those described in other studies from specimens obtained at bronchoscopy. PMID- 1879258 TI - Cytologic interpretation of fine-needle aspiration biopsies from clinically occult breast masses. AB - Fine-needle aspiration biopsy (FNAB) was performed on 39 occult breast masses of soft tissue density using standard mammographic guidance. All malignant tumors were diagnosed as either positive or suspicious for carcinoma, and there were no false-positive or false-suspicious diagnoses. These excellent results can be attributed to accurate cytologic interpretation based on consideration of problems unique to these lesions and the sampling method, such as scantier cellularity, potentially less confidence in needle placement, and the nature of the occult mass itself. The team approach between pathologist, radiologist, and clinician is emphasized. PMID- 1879259 TI - Intraocular fine-needle aspiration biopsy of coronal adenomas. AB - The cytologic findings from intraocular biopsy of coronal adenomas of three previously surgically enucleated eyes were studied. Cohesive clusters of nonpigmented epithelial cells were observed. Clusters of epithelial cells were surrounded by characteristic intercellular matrix material. Coronal adenomas have been clinically mistaken for intraocular melanomas. It is important for pathologists to be familiar with the aspiration cytology of the coronal adenoma to avoid unnecessary enucleation or iridocyclectomy. PMID- 1879260 TI - Cytologic findings in microglandular hyperplasia of the cervix. AB - A case of florid microglandular hyperplasia of the uterine cervix that contained cells with severe atypia suggesting malignancy on a Papanicolaou smear is reviewed. Findings from 25 additional smears from patients with microglandular hyperplasia are reported. These sometimes contained glandular cells with varying degrees of atypia, but demonstrated no features specific for microglandular hyperplasia. The distinction between markedly atypical endocervical cells sometimes exfoliated from microglandular hyperplasia and those of adenocarcinoma is discussed. PMID- 1879261 TI - Fine-needle aspiration cytology of Langerhans' cell histiocytosis (eosinophilic granuloma) of bone in children. AB - Fine-needle aspiration (FNA) cytology of three cases of Langerhans' cell histiocytosis (eosinophilic granuloma [EG]) of bone in children (mean age--8.3 yr; range 5-11 yr) is presented. Two patients presented with vertebral lesions and the third had a femoral mass. Cytomorphologic features of EG were seen in all cases including Langerhans' cell histiocytes having oval to reniform shape nuclei with nuclear grooving and abundant pale cytoplasm. The background showed a polymorphic population of cells including neutrophils, lymphocytes, foamy histiocytes, and osteoclasts. Moderate numbers of eosinophils were seen in two cases, while eosinophils were sparse in the third case. Ancillary immunocytochemical (ICC) studies performed on the aspirated material demonstrated positive staining for S-100 protein (all three cases) and T-6 antigen (one case). Ultrastructural examination (EM) performed in one case demonstrated characteristic Birbeck granules in the histiocytes. A specific cytologic diagnosis was made in all cases, enabling proper chemotherapy in one case, surgical excision in another and spontaneous resolution in the third case. Our experience demonstrates that FNA cytology can make a definitive diagnosis of EG, especially when coupled with ancillary studies such as ICC and EM on the aspirated material. PMID- 1879262 TI - Diagnosis of salivary gland tumors by fine-needle aspiration cytology: a review of clinical utility and pitfalls. AB - Fine-needle aspiration cytology has become a frequently used technique for the diagnosis of neoplasms of the head and neck. While the method has a high sensitivity and specificity for the diagnosis of salivary gland lesions, important pitfalls for the cytologic diagnosis of these lesions exist. This paper discusses the diagnostic pitfalls and investigates strategies for the evaluation of salivary gland masses. PMID- 1879263 TI - Clear-cell change in follicular adenoma mimicking Hurthle-cell tumor on thyroid aspiration biopsy cytology. AB - We present a case of follicular adenoma with clear-cell change, which on fine needle aspiration biopsy mimicked a Hurthle-cell tumor. Papanicolaou-stained smears revealed a monomorphic pattern of loosely cohesive groups of cells with abundant cytoplasm and centrally placed round nuclei with single prominent nucleoli. The cytoplasm was granular or finely vacuolated with occasional intracytoplasmic brown pigment. Subsequent surgical histology of the partial thyroidectomy specimen revealed a follicular adenoma composed of macro- and microfollicles. The microfollicular areas showed clear-cell change: these cells appeared identical to those seen on cytology. No Hurthle-cell change was present in the surgical specimen. Follicular cells with clear-cell change of the granular type must be added to the list of differential diagnoses when cells with Hurthle like features are seen on aspiration biopsy of the thyroid. PMID- 1879264 TI - Aspiration cytology and immunocytochemistry of sacral chordoma with liver metastases: a case report. AB - We present the cytologic features and immunocytochemical profile of a case of sacrococcygeal chordoma metastatic to the liver. Cytologic diagnosis was suspected from the aspiration biopsy smears of the primary sacrococcygeal tumor and confirmed by histology. Further aspirates failed to reveal diagnostic physaliferous cells, and only undifferentiated spindle cells were obtained. Chordoma may lack physaliferous cells: in such cases, immunocytochemistry studies can greatly facilitate the diagnosis. This study confirms the utility of immunocytochemistry in the differential diagnosis of chordoma and tumors with similar cytologic characteristics. PMID- 1879265 TI - Granulomatous mastitis secondary to histoplasmosis: report of a case diagnosed by fine-needle aspiration biopsy. AB - A case of unilateral histoplasmal "granulomatous" mastitis diagnosed by fine needle aspiration biopsy (FNAB) is presented. The clinical presentation and mammographic findings were strongly suspicious for carcinoma. FNAB cytology showed a picture of necrotizing granuloma secondary to histoplasmosis. The lesion was treated with surgical excision and appropriate antifungal therapy. The differential diagnosis of granulomatous mastitis is discussed. PMID- 1879266 TI - Fine-needle aspiration of a solitary pulmonary nodule following treatment of metastatic giant-cell tumor of bone. AB - Giant cell tumor (GCT) of bone is a local, variably aggressive neoplasm with high local recurrence and occasional pulmonary metastases. Radiographically guided fine-needle aspiration (FNA) plays a large role in establishing a tissue diagnosis of lung metastases prior to therapeutic intervention. We present a patient with histologically proven pulmonary metastases from a femoral grade II GCT. These lesions were obliterated with combination HT-CT (hyperthermia and chemotherapy). The patient subsequently developed another pulmonary nodule at a site previously occupied by a GCT metastatic deposit. Radiographically guided FNA revealed that this new lesion was an adenocarcinoma, apparently of pulmonary origin. We suggest that this second neoplasm arose within a scar that developed after HT-CT ablation of one of the metastases. Additional intriguing features of this case are the effective HT-CT therapy of GCT metastatic to lung and the extended temporal course (some 16 yr from initial diagnosis to death). PMID- 1879267 TI - Extracranial metastasis of an astrocytoma detected by fine-needle aspiration: a case report. AB - Extracranial metastasis of gliomas is rare, and the documented cases of extracranial metastasis are based on histological material. A case of metastatic astrocytoma to the soft tissue of the neck and back detected by fine-needle aspiration is reported. Demonstration of glial fibrillary acidic protein by immunoperoxidase technique on aspirated material helped to confirm the diagnosis. PMID- 1879268 TI - Fine-needle aspiration cytology of alveolar soft-part sarcoma. AB - Alveolar soft-part sarcoma (ASPS) is a rare soft-tissue tumor. Few cases have been reported in the aspiration cytology literature. We discuss the fine-needle aspiration (FNA) cytologic features of ASPS in four patients. The smears were characterized by single cells and clusters of cells associated with thin-walled vasculature, resulting in a distinct pseudoalveolar pattern. The cells had abundant granular cytoplasm and large round nuclei with prominent central nucleoli. Binucleated and occasional multinucleated cells were present. Numerous stripped tumor nuclei were a consistent feature. Periodic acid-Schiff (PAS) positive diastase-resistant granules were demonstrable within the intact and fragmented cytoplasm. Electron microscopy of aspirated material identified granules and crystals with the characteristic lattice pattern. To conclude, the FNA cytologic features of ASPS are characteristic. Confirmation by special stains and electron microscopy of FNA material is possible. The differential diagnostic considerations include renal cell carcinoma, paraganglioma, granular cell tumor, clear cell sarcoma, and epithelioid sarcoma. PMID- 1879269 TI - Occult thyroid cancer discovered by fine-needle aspiration cytology of cervical lymph node: a report of three cases. AB - Three cases of occult thyroid cancer measuring 10, 6, and 3 mm in diameter were discovered by fine-needle aspiration cytology of cervical lymph nodes. In these three cases, thyroid tumors were not palpable, and scintigraphic, echographic, and soft-tissue radiologic examinations demonstrated no abnormalities of the thyroid glands. Cytologically, the presence of intranuclear cytoplasmic inclusions, nuclear grooves, and colloid was characteristic in aspirated materials. Histologically, all three cases were diagnosed as papillary carcinoma. Fine-needle aspiration cytology of cervical lymph node was very useful to find occult carcinoma of the thyroid gland. PMID- 1879270 TI - Solitary pleural amyloid nodules occurring as coin lesions diagnosed by fine needle aspiration biopsy. AB - Solitary pleural amyloid nodule is rare and radiologically can mimic neoplastic lesions. This report describes two cases of this entity diagnosed by fine-needle aspiration biopsy in patients without systemic amyloid deposits. The histologic, ultrastructural, and cytologic features are described. PMID- 1879271 TI - Sampling accuracy of the modified Ayre spatula/Zelsmyr Cytobrush versus the modified Ayre spatula/bulb aspirator in the collection of cells from the uterine cervix. AB - An 8-mo (August 1988 through April 1989) study was performed to evaluate the efficacy of the modified Ayre spatula/Zelsmyr Cytobrush versus the modified Ayre spatula/bulb aspirator in the collection of cells, both normal and abnormal, from the uterine cervix. The majority (78%) of the 192 patients, ranging in age from 18 to 82 yr, were referred to the gynecologic/oncologic clinic for follow-up of an atypical Papanicolaou smear or of a previously diagnosed and treated cervical, vulvar, or endometrial lesion. Of the 192 patients, 149 were premenopausal (15 of whom were pregnant), 12 were perimenopausal, and 31 were postmenopausal. Patients were randomized into one of two groups based on the collection of samples for their cervical smears: 1) modified Ayre spatula (exocervix) plus Zelsmyr Cytobrush (endocervix: 90 cases) and 2) modified Ayre spatula (exocervic) plus bulb aspirator (endocervix; 102 cases). Of the smears prepared with the spatula/Cytobrush (90 cases), only 2 (2.2%) lacked endocervical cells. Within this group, the smears of 5 of 5 pregnant patients (100%) and 13 of 13 postmenopausal patients (100%) contained endocervical cells. Cytologic abnormalities were present in 15 of these cases; koilocytosis in 4, cervical intraepithelial neoplasia (CIN)-I in 5, CIN-II in 4, and CIN-III in 2. Five of the 15 cytologically positive cases had histologic verification; the cytologic findings were predictive of the histologic findings in all. Of the smears prepared using the spatula/bulb aspirator (102 cases), 26 (25.5%) lacked endocervical cells. Within this group, the smears of only 4 of 10 pregnant patients (40%) and 14 of 18 postmenopausal patients (78%) contained endocervical cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879272 TI - Massive necrosis: a pitfall in the cytopathologic diagnosis of primary mediastinal seminoma. PMID- 1879273 TI - Aspiration cytology of metaplastic Warthin's tumor mimicking squamous-cell carcinoma. PMID- 1879274 TI - Older adults with diabetes. PMID- 1879275 TI - Nutrition education: the older adult with diabetes. AB - The dietitian, working with other members of the health care team, plays a very important role in developing a care plan for the older person with diabetes. Often individuals in this age group have so many health care needs that nutrition intervention may be low on the priority list. Optimum nutrition is essential to maintain health and well-being as well as to keep blood glucose levels in the target range. The dietitian who works with this population must be very skilled at multifaceted assessment. He or she must be able to correlate all the information gained to creatively design, with the patient and caregivers, a workable dietary intervention, and be able to adapt instruction techniques and tools for a wide variety of educational needs and abilities. Knowledge, skill, experience, confidence in judgment and, most important, sincere caring are all important to the process. Nutrition education should be individually tailored and incorporate patience, kindness, humor, understanding, and above all a respect for the differences that make each older person an individual. PMID- 1879276 TI - Content, construct, and criterion-related validity. PMID- 1879277 TI - Psychosocial contexts of diabetes and older adulthood: reciprocal effects. AB - The present study was conducted to assess the reciprocal effects between the psychosocial contexts of diabetes and older adulthood. Data were collected from 191 community-dwelling adults over the age of 60 with non-insulin-dependent diabetes mellitus. Results indicate that older adults with diabetes reported higher rates of selected chronic illnesses, lower self-rated physical health, and higher levels of depression than did comparison samples of older adults without diabetes. Compared with younger adults with NIDDM, the present sample of older adults perceived fewer impacts of diabetes, including fewer symptoms of poor metabolic control, less emotional impact, fewer barriers to adherence, and less complex regimens. Overall levels of social support and regimen adherence were high. Older adults in this sample reported wanting minimal help from their family and friends with self-management activities and receiving more help than desired with following a meal plan and taking medications. Implications of the unique context of older adulthood for diabetes self-management are discussed. PMID- 1879278 TI - Hardiness and compliance in elderly patients with diabetes. AB - The purpose of this study was to determine if the presence of the hardiness personality characteristic influences compliance. The sample (N = 50) for this study was obtained from a hospital in a large metropolitan area of the United States. The majority of subjects were white, male, married, and diagnosed with type II diabetes. Instruments used to collect data were the Health-Related Hardiness Scale and the Self-Management Compliance Questionnaire. Results indicated that a significant correlation existed between the hardiness and compliance variables. Thirty-six percent of the variance in the compliance score was explained by the total health-related hardiness scores. Findings suggest that the degree of hardiness in individuals with diabetes may predict compliance to a prescribed diabetic regimen. PMID- 1879279 TI - Participation in outpatient diabetes education programs: how many patients take part and how representative are they? AB - Little research has been conducted on the role of participation in programs that teach diabetes self-management skills. This paper reviews recent studies on diabetes educational programs to determine what is known about participation, and then reports our experience in recruiting patients for a program that teaches diabetes self-care skills to persons age 60 and older. Few studies have reported data on participation rates in such programs, and only one study provided information on characteristics of patients who participated versus those who did not. In our study, patients over age 70, and those with whom we initiated contact by means of a letter from their health care provider, were less likely to participate than were younger patients and those who initiated contact with us. It is recommended that future research include information on the percentage and representativeness of patients who participate in diabetes education programs. Studies should also describe their target population, procedures used to recruit participants, and program characteristics that might affect participation. PMID- 1879280 TI - Barriers to the effective use of capillary blood glucose monitoring in extended care facilities. AB - Elderly residents of extended care facilities have an increased prevalence of diabetes compared with age-matched individuals living in the community, and are more prone to uncontrolled hyperglycemia and hypoglycemia. Capillary blood glucose monitoring can provide essential data for managing patients with diabetes, yet blood glucose monitoring is not used consistently by many institutions that provide long-term care. Among the barriers to its use are a perceived lack of validity, a perceived or actual lack of reliability, a failure by staff to use monitoring results consistently, a belief that good control is not necessary for the elderly, and the cost. Educational programs need to be offered to extended care facilities emphasizing the significance of glucose monitoring in the management of diabetes in elderly patients. PMID- 1879281 TI - Exercise: Part II. Translating the exercise prescription. AB - Exercise comes in many forms and uses different substrates (fuels) for adenosine triphosphate (energy) production. The greater the intensity of exercise, the greater the relative contribution of carbohydrate as a fuel source. However, as intensity exceeds the anaerobic threshold, anaerobic glycolysis is inhibited, forcing a decrease in exercise intensity. Proper manipulation of the exercise prescription components can create the desired health and fitness benefits, provide a high level of carbohydrate utilization, and control exercise risks while maintaining exercise intensity at aerobic levels. The calculation of target heart rate zones and proper monitoring of exercise heart rates allows for greater compliance to exercise prescriptions. Individual responses to various exercise intensities and modalities require regular assessments. Monitoring blood glucose levels before and after exercise assists in prescribing exercise duration and exercise times in relation to the medication and dietary regimen. PMID- 1879282 TI - Increasing referrals to diabetes outpatient classes. PMID- 1879283 TI - Diabetes support groups: structure, function, and professional roles. PMID- 1879284 TI - Oral hypoglycemic agents in the management of non-insulin-dependent diabetes mellitus among the elderly. AB - Management of NIDDM among elderly patients is complex due to existing chronic illnesses. Patient education of the potential side effects and drug interactions with oral hypoglycemic agents, as well as good assessment skills help to prevent complications among the elderly population. PMID- 1879285 TI - [Gastric mucosal lesions and their transition rates in high risk population of gastric cancer]. AB - Endoscopic and pathologic examinations were conducted in a randomly chosen population in a high risk area of gastric cancer, Linqu County, Shandong Province. A high prevalence of chronic atrophic gastritis, intestinal metaplasia and dysplasia was found. Gastric mucosal lesions changed from mild to severe with a decline in transition rate. The prevalence rate of severe dysplasia was close to that of gastric cancer. The study indicates that gastric precancerous lesions are related to malignant changes implying that gastric cancer develops on the damaged gastric mucosa. It is also shown that the progression from chronic atrophic gastritis to dysplasia may take an average of 20 years. PMID- 1879286 TI - [Detection of cancer-associated antigen in feces of patients with gastric cancer by monoclonal antibodies]. AB - Detection of cancer-associated antigen in feces was performed by ELISA binding inhibition method using monoclonal antibody in 25 patients with gastric cancer, 70 with non-malignant gastrointestinal diseases and 100 healthy individuals. Monoclonal antibodies used were CL-4, PS-9, PS-10 and a "cocktail" of the three. The level of cancer-associated antigens detected in feces was significantly higher in patients with gastric cancer than in healthy individuals. PS-9 and PS 10 were also significantly higher in gastric cancer than in non-malignant gastrointestinal diseases. The positive rates of CL-4 were 62.5% vs 7.0%, PS-9 44.0% vs 3% and PS-10 64.0% vs 7.0% in patients with gastric cancer and healthy individuals. When the cocktail of the three was used, the positive rates increased to 88.0% and 14% in the above two groups and 26.6% in gastritis group. These results indicate that the detection of cancer-associated antigen in feces is of value in diagnosis of gastric cancer. PMID- 1879287 TI - [Flow cytometric DNA content analysis in thyroid carcinoma]. AB - DNA content and proportion of Phase S cells in 69 paraffin embedded thyroid tumors (15 adenomas and 64 adenocarcinomas) were analysed by flow cytometry. The results showed that 14/15 adenomas were diploid; DNA content was abnormal in 1 papillary adenoma (DNA index 1.14). In the 64 cases of adenocarcinomas, 53 were aneuploid and 11 near diploid. The DNA content and proportion of Phase S cells were closely related to degree of malignancy and prognosis. PMID- 1879288 TI - [Induction of differentiation of human T-cell leukemic cell line (CEM) by phorbol ester]. AB - In the present study, we investigated the effect of phorbol 12-myristate 13 acetate (PMA) on induction of differentiation of human T-cell leukemic cell line (CEM). The results showed that uninduced cells were T1+, T4+, T9+, T10+, T3- and TcR-, representing thymus stage II differentiation. When culturing in vitro with PMA for 5 to 7 days, CEM cells expressed mature T-cell marker (T3) whereas the percentage of cells expressing proliferation-association antigen (T9) was markedly decreased. In addition, PMA could significantly inhibit the growth of CEM cells. We also found that after co-culture with PMA for 2 to 3 days, CEM cells showed distinct morphologic changes. These findings indicate that PMA may induce CEM cells to differentiate towards mature stage. PMID- 1879289 TI - [Killing activity of lymphokine-activated killer (LAK) cells on fresh acute leukemia cells]. AB - In this study, the killing activity of LAK cells on fresh acute leukemia (AL) cells of 13 patients was examined. The LAK cells were prepared from the peripheral blood lymphocytes of 70 normal healthy donors. The results showed that LAK cells have obvious killing activity on AL cells, especially, the acute lymphoblastic leukemia (ALL) cells. The killing activity varies significantly on the same type of AL cells from different patients. Probably, age of patients is one of the influencing factors on this phenomenon. Moreover, the results indicated that the killing activity of LAK cells on AL cells was closely related to the rate of proliferation of AL cells. PMID- 1879290 TI - [Treatment of primary gastric non-Hodgkin's lymphoma]. AB - Fifty-five patients with primary gastric non-Hodgkin's lymphoma were treated in our hospital from 1970 to 1986. The overall 5-year survival rate was 70.5%. For patients with Stages IE and IIE, the 5-year survival rates were 90.5% and 57.1%, respectively. No significant relation to survival was observed concerning sex, age and course of disease. The important prognostic factors of primary gastric non-Hodgkin's lymphoma were: stage, histologic type, depth of invasion and mode of management. Postoperative radiation therapy with or without chemotherapy was better than surgery alone. Total 60Co abdominal irradiation by moving strip technique was better than multifield irradiation. While no evidence was in favor of post-operative radiotherapy plus chemotherapy for stage IE and IIE lesions, multi-disciplinary approach should be considered for patients at high risk of recurrence and metastasis. PMID- 1879291 TI - [Choice of radical gastrectomy type II or III (R2, R3) for gastric cancer and its 5-year survival rate]. AB - Of 453 patients with primary gastric cancer, 364 were treated from 1979 to 1988 by radical gastrectomy type R2 or R3. The 1-year survival rate was 96.2% (329/342), 3-year survival rate 83.2% (283/286) and 5-year survival rate 58.5% (86/147). This 5-year survival rate has significantly been improved as compared with that of our previous reports in 1964 (19.6%) and 1972 (39.5%) as well as those from other institutes in China (30-40%). The improvement of treatment result is due to: 1. Adequate selection and application of radical gastrectomy, Type II or III operation and thorough resection of lymph node (N2, N3) metastasis and abdominal wall invasion, 2. Increased incidence of early lesions, and 3. better follow-up. TNM classification, histologic growth pattern, lymph node metastasis, gross type and site of primary cancer all play significant roles in prognosis. PMID- 1879292 TI - [Clinical characteristics and prevention of positive stump in gastric cancer]. AB - This paper summarizes 80 cases with positive stump among 946 cases of gastric cancer treated by gastrectomy from 1962 to 1986. The positive stump rate was much higher at the esophageal than the duodenal end (12.5% vs 4.5%). It was related to gross type and size of cancer (P less than 0.01). In lesions larger than 5 cm in diameter and of infiltrating type, especially the superficially spreading early cancers by which the gastric mucosa was infiltrated extensively without any clear margin, it was difficult to identify the extent of infiltration and cancer residue due to inadequate resection was likely. In order to avoid a positive stump, 1. total gastrectomy is indicated for cancer of the gastric body or infiltrating type, 2. super-subtotal gastrectomy including the whole lesser curvature or total gastrectomy is indicated for localized lesions larger than 5 cm in diameter at the antrum, and 3. for proximal cancers, the resection line should be set in the esophagus 5 cm beyond the tumor margin and routine examination of the resected specimen should be done during the operation. PMID- 1879293 TI - [Surgical treatment of primary cardiac carcinoma of remnant stomach--a report of 9 cases]. AB - From April 1977 to May 1989, 15 patients with primary cardiac carcinoma of remnant stomach were seen, comprising 1.96% of all carcinoma of gastric cardia during the same period. Thirteen patients were treated by operation and the tumor was resected in 9-1 total gastrectomy with end-to-side esophagojejunostomy and 8 partial cardiectomy with end-to-side esophagogastrostomy. Operative procedure for primary cardiac carcinoma of remnant stomach is discussed with review of literature. PMID- 1879294 TI - [Treatment of advanced liver cancer by autologous and/or homologous LAK cells combined with human natural LL-2]. AB - Ten patients with advanced liver cancer, primary in 5 and metastatic in the other 5, were treated with lymphokine-activated killer cells, autologous (aLAK) and/or homologous (hLAK) combined with human natural IL-2. Each course of treatment lasted 10 days. For aLAK/IL-2 treatment, white cells were collected from the patients to be treated by a cell separator on Day 4 and after 3-day culture of the mononuclear cells in vitro in the presence of IL-2 (500 units/ml), the aLAK cells (1-2 x 10(9)) were transferred back to the patient on Day 7 via the hepatic artery by selective catheterization. IL-2 (20-30 x 10(4) units) was given i.v. daily on Days 1, 2, 8, 9 and 10. For hLAK/IL-2 treatment LAK cells from healthy donors (0.5-1 x 10(9)) were administered i.v. on Days 1, 4, and 7 and IL-2 (20-30 x 10(4) units) i.v. daily on Days 2, 3, 5, 6, 8, 9, 10. Patients with primary liver cancer were all treated with aLAL/IL-2, followed by hLAK/IL-2 in 3. Patients with metastatic cancer in the liver were either treated with hLAK/IL-2 alone or in combination with aLAK/IL-2. The results of the treatment as monitored by B ultrasonography, CT scan and digital selective angiography are as follows: CR in 2 (with metastatic liver cancer), PR in 4 (3 with primary and 1 with metastatic liver cancer), MR in 2 and no response in 2. On follow-up, 7 patients survived greater than 6 months and 1 (a complete responder) for greater than 12 months. Side effects were mild with transient fever up to 38.5 degrees C and general malaise. PMID- 1879295 TI - [Corticosteroid for hemangioma in infants and young children]. AB - 500 infants and young children suffering from hemangioma treated by corticosteroid (Prednisone) are reported. This disorder is most commonly seen in the head and neck (64.2%). Clinically there are 3 types of hemangioma: intradermal (34.1%), subdermal (11.3%), and mixed (51.5%). Our patients were treated with steroid (Prednisone 20-40 mg/QOD at 8 am). All patients were responsive. In 411 evaluated patients, 151 (36.7%) gave CR, 83 (20.1%) gave CR with residual telangiectasis, 172 (41.5%) gave PR, and in 5 patients, the lesion remained or slightly faded. During and within 3 years of treatment, none developed undesirable side effects, though the treatment was protracted to 2 years. PMID- 1879296 TI - [Multiple primary colo-rectal carcinoma--an analysis of 28 cases]. AB - Of 226 cases with colo-rectal carcinoma treated, 21 (7.89%) had synchronous and 7 (2.63%) had metachronous multiple primary lesions. In these 28 cases, 13 (46.43%) were complicated by adenomatous polyp, in which 7 cases (53.85%) became malignant. The tumor in 9 cases (18.75%) of synchronous carcinoma was less than 1 cm in diameter and could not be palpated during operation. The early metachronous carcinoma could be detected by fiberendoscopy during follow-up. Its diagnostic accuracy can be improved by fiberendoscopy before operation and during follow-up. PMID- 1879297 TI - [Clinical manifestations and diagnosis of subarachnoid extraspinal neurilemoma an analysis of 22 cases]. AB - The clinical manifestations of 22 subarachnoid extraspinal neuilemomas are presented and problems related to its diagnosis discussed. Among the 15 cases followed for 5-6 years, 10 were completely cured, 4 cured and resumed work with only some mild symptoms, and one with partial improvement. No recurrence was found. It was emphasized that neurilemomas in the spinal canal may often be confused with protrusion of intervertebral disc because of similar clinical manifestations. The author's suggestion is that in patients with progressively increasing severe pain, scattered points of tenderness on the back, multiple nerve root symptoms or even with saddle numbness, and repeated poor treatment results, further examinations such as CSF, myelography, and if necessary, CT scan should be undertaken for proper diagnosis. PMID- 1879298 TI - [Inhibitory effect of monoclonal antibody PD4 on Ha-ras transformed cells Rat3 3]. AB - McAbPD4 could inhibit the proliferation of transformed cells Rat3-3 with an inhibition rate of 72.3% in vitro. Moreover, McAbPD4 decreased the Rat3-3's colony forming ability on soft agar and tumorigenicity in nude mice. By Flow Cytometry, it was indicated that the inhibitory effect was due to a blockade between G1 and S phase. It was shown by Western Blotting that the McAbPD4-defined antigen was a 40 KD protein, named p40, which was located on the membrane of target cells MGC803 and transformed cells Rat3-3 by immunofluorescence assay. The antigen p40 was highly expressed on Ha-, Ki-, Nb- and Src oncogene transfected cells, but was undetectable or at the best only faintly on cells transformed with mos or raf. The antisense oligonucleotide AS-1 of Ha-ras distinctively inhibited the proliferation of Rat3-3, the level of Ha-ras oncogene product p21 and p40 were decreased by 47.8%, 36.5%, and 52.0%, respectively. The inhibitory effect of AS-1 to GCM3T3 was more marked, each with 54.2%, 47.9% and 65.9%. It is suggested that p40 not only is a tumor-associated antigen, but also a transformation related cell surface protein, which is closely associated with and might be regulated by the activation of ras or Src oncogene and its product. For the inhibitory effect of McAbPD4 to Rat3-3 cells, it is deduced that p40 might be a growth factor receptor mediating autocrine growth of Ha-ras transformed cells. PMID- 1879299 TI - [Immunoelectron microscopic study on the localization of monoclonal antibodies on gastric cancer cells]. AB - The localization of three monoclonal antibodies (mAb) against gastric cancer was studied on two human gastric cancer cell lines by immunoelectron microscopic technique. It was shown that the corresponding antigens of mAb 3G9 and 3H11 were distributed on the microvilli (M) and non-microvillous (NM) plasma membrane of target cells, with varying M to NM ratios depending on the mAbs and target cells used. However, the corresponding antigens of mAb, PD4 was only localized on the surface of round or finger-like bulges of target cells and never on the microvilli and non-microvillous plasma membrane. Since the nature and function of these tumor antigens are yet to be identified, the implication of the different distributions of these tumor antigens remains to be claifated. PMID- 1879300 TI - [Unscheduled DNA synthesis (UDS) induced by N-methyl-N'nitro-N-nitrosoguanidine (MNNG) in human gastric mucosal cells]. AB - DNA repair synthesis as estimated by the unscheduled incorporation of tritiated thymidine (3H-TdR) is a useful, economical, and rapidly performed bioassay for detecting DNA-damaging agents. The purpose of this study was to establish the method of MNNG induction and measurement of UDS in human gastric mucosal cells for further study of gastric carcinogenesis and its prevention. Normal gastric mucosal cells isolated from surgical specimens were exposed to various concentrations of MNNG in the presence of 5mM hydroxyurea and 10uCi/ml 3H-TdR in 1% FBS DMEM-F12 medium for 4 hours at 37 degrees C. Immediately following exposure to MNNG the capacity of gastric mucosal cells to undergo DNA synthesis was assayed by autoradiography. The results of the present study indicated that the gastric epithelial cells are capable of repairing MNNG-induced DNA damage. The UDS positive cells were revealed by increased 3H-TdR incorporation into each nucleus, and the UDS level was MNNG dose-dependent. PMID- 1879301 TI - [Serum and tissue copper, zinc and selenium levels in patients with gastric carcinoma]. AB - Serum and tissue copper, zinc and selenium levels were measured in patients with gastric carcinoma. The mean level of serum copper in patients with gastric carcinoma (42 cases) was 950 +/- 130 ug/L, which was higher than 800 +/- 70 ug/L of the control (30 cases, P less than 0.05). The serum selenium level in patients with gastric carcinoma was lower than that in the control (63 +/- 15 ug/L vs 85 +/- 8 ug/L, P less than 0.05). No significant difference in serum zinc level was found between the patient and control groups. In cancer tissues, the mean concentration of copper was 13.5 +/- 2.6 micrograms/g dry weight, which was much higher than 7.1 +/- 1.6 micrograms/g dry weight in the intact gastric mucosa (P less than 0.01). The activity of superoxide dismutase (SOD) in cancer tissue was 95 +/- 10 u/mg-protein, which was lower than 124 +/- 12 u/mg-protein in the intact gastric mucosa (P less than 0.05). The above changes may facilitate production of free radicals, tissue damage and carcinogenesis. PMID- 1879302 TI - Leukocytosis at the onset of diabetes in crosses of inbred BB rats. AB - Inbred lymphopenic, diabetes-prone (DP) and non-lymphopenic, diabetes-resistant (DR) BB rats in a specific pathogen-free (SPF) colony were subjected to a cross intercross breeding experiment which showed diabetes to segregate as a recessive trait. All DP rats, but none of the DR and F1 rats, developed diabetes. In contrast, about 25% of the F2 rats developed diabetes which made it possible to study these rats without maternal influence of diabetes. All rats were bled at regular intervals between 30 and 150 days of age, and the samples analyzed for numbers of leukocytes, lymphocytes, neutrophils, monocytes and eosinophils. Leukocyte numbers tended to increase with age until about 100 days, and to decline thereafter. Males had more leukocytes than females. Coinciding with the time of onset of overt diabetes, there was a large increase in eosinophils, along with smaller increases in neutrophils, monocytes and lymphocytes. These data in SPF DP and DR BB rats and their cross-intercross offspring demonstrate that the overt onset of diabetes is associated with a significant leukocytosis. PMID- 1879303 TI - The prevalence of microalbuminuria in diabetes: a study from north India. AB - Geographic/population variation in the prevalence of diabetic nephropathy is well recognised. In a study of 'native' Indians, we screened 102 non-proteinuric diabetes mellitus patients (64 NIDDM, 38 IDDM; mean age and diabetic duration 48.7 and 6.5 years, 21.6 and 6.2 years, respectively) with blood pressure less than or equal to 170/105 and without congestive heart failure, ketonuria or urinary tract infection, for the presence of microalbuminuria (albumin excretion rate greater than 20 micrograms/min). Fifty-six patients (34 NIDDM, 22 IDDM) also underwent detailed fundus examination. Seventeen NIDDM (26.6%) and 3 IDDM (7.9%) patients had microalbuminuria. Glycated hemoglobin was significantly higher in microalbuminurics in the NIDDM group (P less than 0.05). Diabetic retinopathy tended to occur more frequently in microalbuminurics (NIDDM and IDDM). PMID- 1879304 TI - Management of newly diagnosed non-insulin-dependent (type 2) diabetes mellitus: a retrospective audit. AB - A retrospective survey of the case records of 130 patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) was performed to assess the effect of 1 year of clinical attendance on blood glucose control, body weight, lipid profile and blood pressure. The mean age of these patients was 63 +/- (SE) 0.1 years and 45% were 65 years or older. Body mass index (BMI) was 28.3 +/- 0.49 kg m-2 and 72% were overweight or obese. Sixty-seven percent of the patients were hypertensive (WHO criteria). Serum cholesterol was 6.0 +/- 0.2 mmol/l, HDL cholesterol 1.0 +/- 0.0 mmol/l and triglycerides 3.14 +/- 0.29 mmol/l (non fasting). Seventy-two percent of the patients were managed on diet alone and 23% by diet plus sulphonylurea. The remaining 5% were treated by metformin or a combination of metformin plus sulphonylurea. After one year, glycated haemoglobin (HbA1) decreased from 10.7 +/- 0.3% to 8.2 +/- 0.2% (P less than 0.01; normal less than 7.5%). The sulphonylurea groups showed similar decreases in HbA1. Overall there was a small but significant fall in BMI (-0.5 +/- 0.2 kg m-2; P less than 0.05). However, the diet treated patients showed a significant decrease in BMI (-0.8 +/- 0.3 kg m-2; P less than 0.01) whilst BMI increased in the sulphonylurea treated group (+0.7 +/- 0.2 kg m-2; P less than 0.01). Serum lipid concentrations remained unchanged in both groups. The proportion of patients with hypertension remained the same. Hence after one year of clinical attendance, HbA1 improved but there was minimal change in the associated cardiovascular risk factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879305 TI - A case of insulin allergy: the crystalline human insulin may mask its antigenicity. AB - We report an unusual case of insulin allergy. A 48-year-old man with non-insulin dependent diabetes mellitus receiving biosynthetic isophane human insulin (Humulin N) developed itchy wheal-and-flare reactions at the sites of injection. When Humulin N was changed to a semi-synthetic crystalline human insulin zinc (Novolin U), the allergic reactions completely disappeared. Evaluation of his serum showed a high level of insulin-specific IgE. Skin testing with all commercially available insulins showed immediate local reactions to all agents tested except for Novolin U. In addition, decrystallized Novolin U prepared by lowering the pH with acetic acid also induced a positive reaction. These observations suggest that the crystallized structure of human insulin may mask its antigenicity for allergic reactions. PMID- 1879306 TI - Intranasal administration of insulin to humans. AB - The purpose of this review is to summarize the information and experience at present available on the intranasal administration of insulin to human subjects and to describe some of the anatomical, physiological, pharmaceutical and technological factors which can affect the absorption of insulin. An overview is given of those absorption promoters which have been used in clinical insulin studies, and the possible absorption-promoting mechanisms are discussed. This review shows that the nasal route offers a promising alternative to parenteral administration. The easier administration and the acceptance by the patients is encouraging the development of new intranasal insulin preparations. PMID- 1879307 TI - Low prevalence of microalbuminuria in normotensive patients with insulin dependent diabetes mellitus. AB - We studied the prevalence of microalbuminuria (urinary albumin excretion rate [UAER] greater than 20 micrograms/min less than or equal to 200 micrograms/min) as determined in a single, timed, overnight urine collection in 156 normotensive (BP less than 140/90), Albustix negative subjects with type 1 diabetes and its association with arterial blood pressure, the duration of diabetes, levels of glycosylated hemoglobin, body mass index, daily insulin dose and serum cholesterol. Nineteen subjects (12.2%) had a UAER in the microalbuminuric range. The microalbuminuric patients had a significantly longer duration of diabetes, 21 +/- 2 vs 15 +/- 1 years (P less than 0.01), higher diastolic blood pressure, 80 +/- 2 vs 76 +/- 1 mmHg (P less than 0.05) and serum cholesterol concentration, 206 +/- 11 vs 186 +/- 3 mg/dl (P less than 0.05) than did the normoalbuminuric subjects. There were no differences between the normoalbuminuric and microalbuminuric subjects in terms of age, systolic blood pressure, body mass index, daily insulin dose or glycosylated hemoglobin levels. These data indicate that the prevalence of microalbuminuria in type 1 diabetes has probably been overestimated in previous studies due to the inclusion of patients with hypertension. Thus, microalbuminuria, rather than being a predictor of the development of diabetic renal disease, may indicate the presence of diabetic nephropathy with rising blood pressure levels. Further investigation is needed to clarify the relationship between microalbuminuria and coronary risk factors such as serum cholesterol and diastolic blood pressure levels. PMID- 1879308 TI - Decreased hepatic insulin extraction in upper body obesity: relationship to unbound androgens and sex hormone binding globulin. AB - Hyperinsulinemia is a well-recognized entity of simple obesity. It is demonstrated that hyperinsulinemia is associated with upper body fat and fat cell hypertrophy. Androgen excess and lower levels of sex hormone binding globulin (SHBG) may produce fat cell hypertrophy and hyperinsulinemia as well. We measured serum insulin and C-peptide levels during an OGTT in two groups of obese premenopausal women to determine whether the hyperinsulinemia is due to hypersecretion or due to a diminished hepatic extraction of insulin. In this study, we found no correlation between the insulin and C-peptide levels or their ratio and the degree of obesity. However, a significant correlation was found between the waist-to-hip circumference ratio (WHR), used as an index of body fat distribution, and the areas of insulin (r = 0.55; P less than 0.001) and C peptide (r = 0.51; P less than 0.001). SHBG and free androgen index (FAI) were also significantly related to these areas. The peripheral C-peptide/insulin molar ratio has been assumed to reflect changes in hepatic insulin extraction while the corrected C-peptide response reflects beta-cell function. WHR was negatively related to this ratio (r = -0.44; P less than 0.005) and SHBG showed a positive correlation (r = 0.34; P less than 0.05). Stepwise multiple regression analysis revealed that the 2-h insulin and C-peptide values and both curve areas can be explained up to 40-80% by sex hormones and anthropometric variables. Also the C peptide/insulin molar ratio is dependent in a first step on WHR (r2 = 0.23; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879309 TI - [The effects of nifedipine, diltiazem, and Paeonia lactiflora Pall. on atherogenesis in rabbits]. AB - The effects of nifedipine, diltiazem, and Paeonia lactiflora Pall (PLP) on serum lipids. Plasma lipid peroxides (LPO), TXB2, and 6-keto-PGF1 alpha in cholesterol fed rabbits have been investigated. Oral administration of nifedipine (15 mg/kg.d), diltiazem (30 mg/kg.d), and PLP (5 g/kg.d) caused 60.8%, 45.2%, and 74.2% reduction in the area of atherosclerosis in the aorta respectively. The levels of plasma LPO and TXB2 and the contents of cholesterol, phospholipid, and calcium in the intimal-media of the aorta in the treated groups were significantly lower than those in the cholesterol group, but the level of plasma 6-keto-PGF1 alpha in the treated groups was significantly higher. The appearance of cholesterol-induced TXB2 elevation and 6-keto-PGF1 alpha decrease in the treated groups was delayed. There are positive correlation between plasma TXB2 and the followings: serum lipids, plasma LPO, and the content of calcium in the intimal-media of the aorta, and the percentage of area of lesion in the aorta, while plasma 6-keto-PGF1 alpha showed significantly negative correlation with the above data. TXB2/6-keto-PGF1 alpha was found to be positively correlated with the percentage of lesion area of the aorta. It was shown that Ca2+ metabolism plays an important role in thromboxane, prostaglandin, and LPO metabolism. In conclusion, the inhibition of LPO production and regulation of TXA2-PGI2 balance may be one of the main mechanisms of the antiatherogenic effects of calcium antagonists and PLP. PMID- 1879310 TI - [The effect of nisoldipine on ischemic myocardial injury in monkeys]. PMID- 1879312 TI - [Clinical types of trifascicular block and a follow-up study of pacemaker application]. AB - Thirty five patients (pts) with trifascicular block (TFB) were followed up for 5 years, and indication of pacemaker and clinical types of TFB were discussed. All of the 35 pts were diagnosed with clinical, ECG monitoring and His bundle electrogram (HBE) and classified into 4 groups: (1) acute transient TFB (3 cases) characterized by RBBB + LAHB + I or II AVB, caused by acute myocarditis or AMI, recovered with medicinal treatment; (2) 4 cases of acute advanced TFB characterized by RBBB + LAHB or LAPB + III AVB with severe symptoms such as syncope and Adams-Stokes syndrome; (3) 12 cases of chronic TFB characterized by RBBB + LAHB or LPHB + I, II or III AVB, with 40 beats/min lower heart rate and severe symptoms; (4) 18 cases of chronic advanced TFB characterized by RBBB + LAHB or LPHB + 1, 11 or III AVB, with severe symptoms. The 32 pts in groups 2, 3, and 4 were treated with implanted pacemakers and recovered very well. 29 pts are still well with pacemakers, and 5 cases with cardiomyopathy died due to chronic heart failure during the follow-up period of 5 years. CONCLUSION: all of the pts with TFB and severe symptoms treated with pacemakers were appropriate, and are living well except those with chronic heart failure. PMID- 1879311 TI - [Electrophysiological properties of atrial fibrillation with WPW syndrome and the role of procainamide in conversion]. AB - Fifty one patients with recurrent episodes of atrial fibrillation associated with WPW syndrome were studied by pre-operative clinical electrophysiogical testing. The results showed that: these patients had an markedly prolonged intra-atrial conduction time (PA intervals: 42.22 +/- 10.93 ms) than the patients only with attack of atrioventricular reentry tachycardia (AVRT) (PA intervals: 17.21 +/- 9.68ms, P less than 0.001). The attack of atrial fibrillation related to an markedly prolonged atrial vulnerable phase and the retrograde conduction of accessory pathway (AP). The clinical results of atrial fibrillation were decided by the antegrade effective refractory period (AERP) of AP. When the shortest R-R (V-V) intervals during attack of atrial fibrillation was shorter than 180ms, the atrial fibrillation spontaneously turned to the ventricular fibrillation. The conversion of atrial fibrillation to sinus rhythm showed that procainamide not only prolonged AERP of AP, which were 248.57 +/- 15.74ms and 388.57 +/- 63.9 ms (P less than 0.001) respectively before and after intravenous procainamide infusion, but also prolonged intra-atrial conduction time significantly, the PA interval before and after intravenous procainamide infusion were 42.22 +/- 10.93 ms and 57.14 +/- 11.12 ms (P less than 0.025) respectively. PMID- 1879313 TI - [The effects of mexiletine on paroxysmal supraventricular tachycardia]. PMID- 1879314 TI - [The experimental ablation of ventricular tachycardia in dogs with intracoronary ethyl alcohol injection]. AB - In 15 anesthetized dogs, a diagonal branch of the left anterior descending coronary artery was cannulated. Localized ventricular tachycardia (VT) was induced by injecting aconitine solution into the left ventricular wall perfused by the cannulated diagonal branch. In 6 untreated control dogs, VT lasted 17.6 +/ 8.3 minutes, 3 of them degenerated into ventricular fibrillation. The VTs were eliminated in 8 of the 9 dogs (88.9%) 1.2 +/- 1.4 minutes after injection of 96% ethyl alcohol. The pathologic examination revealed that transmural myocardial necrosis was present in 7 of 9 dogs receiving alcohol injection. Fibrin or thrombus was present in the diagonal coronary branch in 5 dogs. The conclusion was that the intracoronary injection of 96% ethyl alcohol ablated aconitine induced ventricular tachycardia effectively. This approach may become a promising new method to treat ventricular tachycardia or other arrhythmia. PMID- 1879315 TI - [Experimental study of laser ablation on lethal arrhythmias in dogs]. AB - To study the effect of laser ablation on arrhythmogenic ventricular myocardium, we applied aconitine on 36 local epicardial sites of ventricles (22 in LV, 14 in RV) in 12 dogs. Severe monographic persistent VTs or VFs were induced by aconitine and then these foci were irradiated by Nd: YAG laser. RV refractoriness (RVR) and local epicardial pacing threshold (LEPT) were measured by programmed electrical stimulation (PES) before aconitine applying and after resuming sinus rhythm. That VT or VF could not be induced by PES and the heart had persistent sinus rhythm was considered success. Aconitine doses were 7.9 +/- 4.8 micrograms in LV, 3.3 +/- 1.9 micrograms in RV, P less than 0.01. The data of time from aconitine applying to the appearance of VT were 237 +/- 228 s in LV and 148 +/- 101 s in RV, P less than 0.05. VF incidence rate was 75% (27/36). All of VT, VF could be abolished by mapping-guided laser irradiation on VT foci. The mean laser energy was 1542 +/- 893 joules (n = 36). RVR and LEPT increased significantly (P less than 0.001) after tests. Results showed that: (1) Lethal ventricular arrhythmias could be induced by giving little aconitine on the ventricular epicardium; (2) Mapping-guided lasering on arrhythmogenic myocardium could eradicate VT and VF; (3) RVR and LEPT would increase greatly after ablation. PMID- 1879316 TI - [1:2 atrioventricular conduction of dual pathway in atrioventricular node]. PMID- 1879317 TI - [A case of focal resection in refractory ventricular tachycardia]. PMID- 1879318 TI - [Clinical application of image processing system and quantitative analysis of left ventriculogram and coronary arteriogram]. AB - Currently cine left ventriculography and coronary arteriography are still one of the most important methods in the diagnosis of coronary heart disease and other coronary arterial diseases. An image processing system, called "IA-87 Medical Image Processing System", for quantitative analysis of cine-coronary and left ventricular angiograms has been developed using IBM-PC/AT computer. The major functions of this system are: (1) left ventricular volume determination, i.e. left ventricular contour can be drawn automatically or semi-automatically, the systolic and diastolic volume of the left ventricle are calculated by Simpson's, length-area and chord-length methods. (2) left ventricular segmental wall motion analysis, using rectilinear and polar method, the segmental ejection fraction and normalized segmental contraction are determined. (3) dynamic display of the cardiac cycle. (4) coronary arterial lesion, such as stenosis, can be quantitatively analysed. In a series of cases free from cardiac disease the normal coronary artery (40 cases) and left ventricle (30 cases) were quantitatively analysed using "IA-87 Medical Image Processing System", and the normal value of coronary artery diameter and left ventricular function among Chinese obtained. At the same time, in a series of 45 cases with coronary heart disease (including anterior, posterior wall infarction, and left ventricular aneurysm in 15 respectively), quantitative analysis of the left ventricle was made. The results showed that the system is of significant value for quantitative diagnosis of ischemic heart disease as well as evaluation of therapeutic effect and prediction of prognosis. PMID- 1879319 TI - [Quantitative analysis of coronary arteriogram by a computer-assisted method]. AB - A computer-assisted method for quantitating coronary arteriograms was applied to measure the diameter of major epicardial coronary arteries in 58 normal subjects and 25 hypertensive patients, and to determine the percentage of relative stenosis of coronary lesions in 109 patients with coronary artery disease. Average coronary size was larger than normal in patients with hypertension. The left coronary artery was larger than the right coronary artery in the majority of patients. The degree of coronary stenosis can be measured accurately with good reproducibility. Thus this inexpensive microprocessor system provides rapid quantitation of coronary artery diameter and lesions. PMID- 1879320 TI - [Management of postoperative arrhythmia after open heart surgery in complex congenital heart disease]. AB - The incidence of postoperative arrhythmia was 35.2% in 264 cases with complex congenital heart diseases underwent open heart surgery between Feb, 1988 and Aug, 1989. Postoperative arrhythmia was closely related to preoperative hematocrit, cardiomegaly, prolonged aortic occlusion, ratio of RV/LV systolic pressure greater than 0.75, hypokalemia and low cardiac output syndrome. Infusion of colloid solution and both potassium and magnesium as well as successful surgery and the preventive administration of antiarrhythmic agent played an important role in the prevention and treatment of postoperative arrhythmia. PMID- 1879321 TI - [Long-term culture and a morphological study of endothelial cells from human aorta]. AB - Endothelial cells from human aorta were successfully cultured first in this Lab in our country. Cells survived and passed through 10-15 generations. Long term cultured endothelial cells from human aorta were observed under phase-contrast microscope, scanning, transmission electron microscope, and investigated immunocytochemically by immunofluorescence of specific antibody against Factor VIII related surface antigen, and ABC method using monoclonal antibody 9B9 against human angiotensin-converting enzyme. Medium RPMI-1640 supplemented with 20% human serum, endothelial cell growth factor 200 micrograms/ml, heparin 100 micrograms/ml and gelatin coated flasks were very important conditions for long term culture of human endothelial cell. PMID- 1879322 TI - [Gallstone treatment by electrohydraulic extracorporeal shockwave lithotripsy]. AB - Extracorporeal shockwave lithotripsy (ESWL) with an electrohydraulic system was performed in 124 patients (33 men, 91 women; mean age 50.1 +/- 12.7 years). Sufficient stone fragmentation was achieved in 122 patients (98.3%). ESWL was repeated in 29 patients (23.3%), twice in 7 patients (5.6%). Average shockwave application per patient was 1,441 +/- 414 impulses, at a mean energy of 20.0 +/- 1.6 kV. Mean stone diameter before ESWL was 16.2 +/- 4.2 (7-30) mm, 7.1 +/- 4.1 (0-19) mm after ESWL. Computed tomography, performed immediately after ESWL in 88 patients demonstrated hypodense thickening (3-10 mm) of the gallbladder wall in 28.4% of patients. This was interpreted as wall oedema, reversible in all. One patient had a covered gallbladder rupture and two had biliary pancreatitis. None of the patients required emergency surgery. 93 patients (74.9%) had no stones 12 months later. A high success rate can be achieved if certain criteria are adhered to and suitable patients are selected. PMID- 1879323 TI - [The clinical course of coumarin-induced necrosis]. AB - In three patients painful reddening of a well-circumscribed area of the skin occurred within five days of starting anticoagulant treatment with phenprocoumon (Marcumar), and within a short time it developed into a full-blown picture of coumarin necrosis. The indication for phenprocoumon was, in the first patient (a 29-year-old mother lying-in after her second child had been born) an increased platelet count and the presence of high risk factors for thromboembolism. In the second patient (25-year-old man) and the third one (45-year-old woman) it was secondary prophylaxis after pulmonary embolus and deep-vein thrombosis, respectively. All three patients were very obese and had a drug allergy, as well as other allergies (bronchial asthma in Cases 1 and 2; allergic rhinitis in Case 3). Phenprocoumon was at once discontinued in all three patients and low-dose heparin administration (Cases 1 and 3) or dextran infusion (Case 2: heparin intolerance) started. All three needed excision of the necrotic tissue with grafting to the skin defect. The coexistence of obesity and allergic diathesis may thus present an especially high risk for coumarin necrosis. PMID- 1879324 TI - [The diagnosis of arrhythmias in hypertrophic cardiomyopathy]. PMID- 1879325 TI - [The pathophysiology, clinical picture and treatment of coumarin-induced necrosis]. PMID- 1879326 TI - [Mitral valve prolapse: a risk in the sauna?]. PMID- 1879327 TI - [Molds in the masonry]. PMID- 1879328 TI - [Dioxins]. PMID- 1879329 TI - [Complete anuria in unilateral renal artery obstruction and ischemic nephropathy]. PMID- 1879330 TI - [An allergy to mistletoe extract]. PMID- 1879331 TI - [Bone marrow transplantation in AL amyloidosis?]. PMID- 1879332 TI - [Metastasizing breast carcinoma]. PMID- 1879333 TI - Colonization of the post-umbilical bowel by cells derived from the sacral neural crest: direct tracing of cell migration using an intercalating probe and a replication-deficient retrovirus. AB - Experiments were done to test the hypothesis that the avian gut is colonized by cells derived from both vagal and sacral regions of the neural crest. A fluorescent dye, diI (1,1-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), and a replication-deficient retrovirus (LZ10; Galileo et al. 1990) were employed as tracers. Since LZ10 was constructed with lacZ of E. coli as a reporter gene, infected cells were identified by demonstrating beta-galactosidase immunoreactivity. DiI and LZ10 were injected between the neural tube and surface ectoderm (before the migration of crest cells away from the injection sites) at vagal, truncal (diI only), or sacral axial levels. The bowel was examined 4 days later in order to allow crest-derived cells sufficient time to migrate to the gut. Following injections of either tracer into the vagal crest, labelled cells were found in the gizzard and duodenum. When diI or LZ10 was injected into the sacral crest, labelled cells were seen in the post-umbilical bowel and ganglion of Remak. In the hindgut, marked cells were concentrated in the mesenchyme, just internal to the serosa, and were never observed rostral to the umbilicus. No fluorescent cells were ever found in the bowel following truncal injections of diI, although such cells were observed in sympathetic ganglia. Labelled cells were always found in dorsal root ganglia, no matter which tracer or level of the crest was injected. In embryos injected with LZ10, infected cells in the gut and dorsal root ganglia displayed a neural crest marker (NC-1 immunoreactivity). These observations confirm that the gut is colonized by cells from the sacral as well as the vagal region of the neural crest and that the emigres from the sacral crest are confined to the post-umbilical bowel. PMID- 1879334 TI - Positioning and maintenance of embryonic body wall muscle attachments in C. elegans requires the mup-1 gene. AB - As part of a general study of genes specifying a pattern of muscle attachments, we identified and genetically characterised mutants in the mup-1 gene. The body wall muscles of early stage mup-1 embryos have a wild-type myofilament pattern but may extend ectopic processes. Later in embryogenesis, some body wall muscles detach from the hypodermis. Genetic analysis suggests that mup-1 has both a maternal and a zygotic component and is not required for postembryonic muscle growth and attachment. mup-1 mutants are suppressed by mutations in several genes that encode extracellular matrix components. We propose that mup-1 may encode a cell surface/extracellular matrix molecule required both for the positioning of body wall muscle attachments in early embryogenesis and the subsequent maintenance of these attachments to the hypodermis until after cuticle synthesis. PMID- 1879335 TI - Mitogenic activity of chicken chorioallantoic fluid is temporally correlated to vascular growth in the chorioallantoic membrane and related to fibroblast growth factors. AB - The chorioallantoic membrane (CAM) is one of the most vascularized tissues in the chicken embryo. Capillary growth proceeds until day 10 of development and thereafter abruptly regresses. As it is generally accepted that the formation of new blood vessel is regulated by growth factors, we have investigated the presence of angiogenic and mitogenic factors in the chicken chorioallantois. In the present study, we show that chorioallantoic fluid (CAF) contains angiogenic substances that are probably synthesized in the CAM or the embryonic kidney. When applied in the chorioallantoic membrane assay, CAF from 9 day chicken embryos elicits a strong angiogenic response. This angiogenic activity of CAF is associated with pronounced mitogenic effects in vitro. Comparison of different embryonic fluids reveals that mitogenic activity is particularly evident in the CAF but not detectable in embryonic serum and amnion fluid. Expression of mitogenic activity is found to be temporally correlated with vascular growth in the CAM. High activity is detected in CAF prior to day 10 and then sharply decreases, thus preceding termination of capillary growth by one day. Heparin sepharose affinity chromatography suggests that the biological activities of CAF probably correspond to the presence of acidic and basic fibroblast growth factor (aFGF and bFGF). In Western blot analyses of CAF, an immunoreactive bFGF-like protein of about 17 x 10(3) Mr is recognized by a monospecific anti-bFGF antiserum. This protein elutes at 2.4 M NaCl from the heparin-sepharose. The mitogenic activity of the CAF can be specifically blocked by the anti-bFGF antibody indicating bFGF to be the active mitogenic principle of the CAF. These results strongly suggest that basic and probably acidic FGF play an important role in the regulation of chorioallantoic vascular growth. PMID- 1879336 TI - Differential expression of type I and type III collagen genes during tooth development. AB - Collagen gene expression during mouse molar tooth development was studied by quantitative in situ hybridization techniques. Different expression patterns of type I and type III collagen mRNAs were observed in the various mesenchymal tissues that constitute the tooth germ. High concentration for pro-alpha 1(I) and pro-alpha 2(I) collagen mRNAs were found within the osteoblasts. We found that the cellular content of type I collagen mRNAs in the odontoblasts varies throughout the tooth formation: whereas mRNA concentration for pro-alpha 1(I) collagen decreases and that of pro-alpha 2(I) increases, during postnatal development. Moreover, different amounts of pro-alpha 1(I) and pro-alpha 2(I) collagen mRNAs were observed in crown and root odontoblasts, respectively. Type III collagen mRNAs were detected in most of the mesenchymal cells, codistributed with type I collagen mRNAs, except in odontoblasts and osteoblasts. Finally, this study reports differential accumulation of collagen mRNAs during mouse tooth development and points out that type I collagen gene expression is regulated by distinct mechanisms during odontoblast differentiation process. These results support the independent expression of the collagen genes under developmental tissue-specific control. PMID- 1879338 TI - The spatial and temporal distribution of polarizing activity in the flank of the pre-limb-bud stages in the chick embryo. AB - The presence of polarizing activity in the limb buds of developing avian embryos determines the pattern of the anteroposterior axis of the limbs in the adult. Maps of the spatial distribution and the strength of the signal within limb buds of different stages are well documented. Polarizing activity can also be found in Hensen's node in the early embryo. We have mapped the distribution of polarizing activity as it emerges from Hensen's node and spreads into the flank tissue of the embryo. There is a clear change in the local pattern of expression of polarizing activity between stage 8 and 18. Almost no activity is measured for stages 8 and 9. More or less uniform levels of around 10% are spread along the flank lateral to the unsegmented somitic mesoderm from somite position 12 to 22 in stage 10 embryos. Some 6 to 8 h later at stage 12, there is a distinct peak of activity at somite position 18, the middle of the wing field. This peak increases at stages 13 to 15 and its position traverses to the posterior edge of the wing field. Full strength of activity is reached shortly before the onset of limb bud formation at stage 16 to 17. Stages 16 to 18 were investigated for polarizing activity in the wing and the leg field. Low levels of polarizing activity are present in the anterior leg field at stages 16 and 17 but have disappeared by stage 18 and all activity is confined to the posterior part of the leg bud. PMID- 1879337 TI - The relationship between cell proliferation and the transcription of the nuclear oncogenes c-myc, c-myb and c-ets-1 during feather morphogenesis in the chick embryo. AB - We have described the expression of three nuclear protooncogenes, c-myc, c-myb and c-ets-1 during feather morphogenesis in the chick embryo. In parallel with the expression patterns obtained by in situ hybridization, we have mapped the spatial distribution of S-phase cells by monitoring the incorporation of 5 bromodeoxyuridine. We do not detect c-myc or c-myb transcripts during the early stages when S-phase cells are scattered in the dermis and in the epidermis. Rather c-ets-1 transcripts are abundant in the dermal cells which divide and accumulate under the uniform epidermis. At the onset of the formation of the feather bud, cells within each rudiment cease DNA replicative activities and c myc transcripts are detected both in the epidermis and in the underlying dermis. This expression precedes the reentry into the S phase. The transcription of c myb, which has been previously tightly linked to hemopoietic cells is also detected in the developing skin. This expression is essentially located in proliferating epidermal cells on and after the beginning of feather outgrowth. As feather outgrowth proceeds, the distribution of c-myc and c-myb transcripts is restricted to the highly proliferating epidermis. In contrast c-ets-1 transcripts are never detected in the epidermis. During the later stages of skin morphogenesis, the transcription of c-ets-1 is restricted to the endothelial cells of blood vessels, as previously described. We suggest that the differential expression of these nuclear oncogenes reflects the activation of different mitotic controlling pathways during the development of the skin. PMID- 1879339 TI - The effect of a heterochronic mutation, Teopod2, on the cell lineage of the maize shoot. AB - Teopod2 (Tp2) is a semi-dominant mutation of maize that prolongs the expression of characteristics normally confined to the juvenile phase of development. Two of the many dramatic morphological effects of this mutation are an increase in the number of vegetative nodes, and a reduction in the overall size of the shoot. To determine the cellular basis of these phenotypes, the technique of clonal analysis was used to compare the cell division patterns of wild-type and Tp2 plants. Our results indicate that Tp2 increases the number of vegetative nodes produced by the apicalmost cells in the meristem but does not affect the cell lineage of the basal, juvenile, part of the shoot. This result demonstrates that Tp2 does not act uniquely in a 'juvenile' domain of the meristem, but instead causes cells that are normally destined to produce adult structures to express juvenile traits inappropriately. Clonal analysis also demonstrates that Tp2 does not affect the size of the meristem prior to germination, nor does it affect the cell lineage of the basic structural unit of the stem, the phytomer. Thus the effects of this mutation on the size of the shoot are the result of changes in cell fate late in development. PMID- 1879340 TI - Genetically identical parthenogenetic mouse embryos produced by inhibition of the first meiotic cleavage with cytochalasin D. AB - The microfilament inhibitor cytochalasin D inhibits extrusion of the first polar body when present during the first meiotic division of mouse oocytes; however, it does not interfere with anaphase movement of chromosomes, and thus induces the formation of tetraploid oocytes. After the separation of chromosomes in anaphase, two spindles start to assemble. However, they merge rapidly and a single meiotic spindle forms. During the transition between metaphase I and metaphase II, in the presence of cytochalasin D, a drop in histone kinase activity takes place demonstrating a transitional decrease in the activity of the maturation promoting factor. These oocytes can be activated parthenogenetically a few hours after washing out the inhibitor. After completion of the second meiotic division and extrusion of a polar body, they contain a diploid number of chromosomes. They are genetically identical to each other and to their mother. Such eggs develop to the blastocyst stage and can implant in the uteri of foster mothers. Most of these fetuses die before the 9th day of gestation, as do diploid control fetuses treated with cytochalasin D during the second meiotic division. The heterozygous state of the experimental embryos obtained after activation of eggs recovered from heterozygous females and treated with cytochalasin D during the first meiotic division was confirmed using a glucose-phosphate isomerase assay. This technique allows the production of genetic clones of parthenogenetic embryos by simple means. PMID- 1879341 TI - An analysis of culmination in Dictyostelium using prestalk and stalk-specific cell autonomous markers. AB - The ecmA (pDd63) and ecmB (pDd56) genes encode extracellular matrix proteins of the slime sheath and stalk tube of Dictyostelium discoideum. Using fusion genes containing the promoter of one or other gene coupled to an immunologically detectable reporter, we previously identified two classes of prestalk cells in the tip of the migrating slug; a central core of pstB cells, which express the ecmB gene, surrounded by pstA cells, which express the ecmA gene. PstB cells lie at the position where stalk tube formation is initiated at culmination and we show that they act as its founders. As culmination proceeds, pstA cells transform into pstB cells by activating the ecmB gene as they enter the stalk tube. The prespore region of the slug contains a population of cells, termed anterior-like cells (ALC), which have the characteristics of prestalk cells. We show that the ecmA and ecmB genes are expressed at a low level in ALC during slug migration and that their expression in these cells is greatly elevated during culmination. Previous observations have shown that ALC sort to surround the prespore cells during culmination (Sternfeld and David, 1982 Devl Biol. 93, 111-118) and we find just such a distribution for pstB cells. We believe that the ecmB protein plays a structural role in the stalk tube and its presence, as a cradle around the spore head, suggests that it may play a further function, perhaps in ensuring integrity of the spore mass during elevation. If this interpretation is correct, then a primary role of anterior-like cells may be to form these structures at culmination. We previously identified a third class of prestalk cells, pstO cells, which lie behind pstA cells in the slug anterior and which appeared to express neither the ecmA nor the ecmB gene. Using B-galactosidase fusion constructs, which give more sensitive detection of gene expression, we now find that these cells express the ecmA gene but at a much lower level than pstA cells. We also show that expression of the ecmA gene becomes uniformly high throughout the prestalk zone when slugs are allowed to migrate in the light. Overhead light favours culmination and it may be that increased expression of the ecmA gene in the pst 'O' region is a preparatory step in the process. PMID- 1879342 TI - Expression of a novel Muller glia specific antigen during development and after optic nerve lesion. AB - To generate monoclonal antibodies, immunogen fractions were purified from embryonic chick retinae by temperature-induced detergent-phase separation employing Triton X-114. Under reducing conditions, the monoclonal antibody (mAb) 2M6 identifies a protein doublet at 40 and 46 x 10(3) Mr, which appears to form disulfide-coupled multimers. The 2M6 antigen is regulated developmentally during retinal histogenesis and its expression correlates with Muller glial cell differentiation. Isolated glial endfeet and retinal glial cells in vitro were found to be 2M6-positive, identified with the aid of the general glia marker mAb R5. mAb 2M6 does not bind to any other glial cell type in the CNS as judged from immunohistochemical data. Cell-type specificity was further substantiated by employing retinal explant and single cell cultures on laminin in conjunction with two novel neuron-specific monoclonal antibodies. MAb 2M6 does not bind either to neurites or to neuronal cell bodies. Incubation of retinal cells in vitro with bromodeoxyuridine (BrdU) and subsequent immunodouble labelling with mAb 2M6 and anti-BrdU reveal that mitotic Muller cells can also express the 2M6 antigen. To investigate whether Muller cell differentiation depends on interactions with earlier differentiating ganglion cells, transections of early embryonic optic nerves in vivo were performed. This operation eliminates ganglion cells. Muller cell development and 2M6 antigen expression were not affected, suggesting a ganglion-cell-independent differentiation process. If, however, the optic nerve of juvenile chicken was crushed to induce a transient degeneration/regeneration process in the retina, a significant increase of 2M6 immunoreactivity became evident. These data are in line with the hypothesis that Muller glial cells, in contrast to other distinct glial cell types, might facilitate neural regeneration. PMID- 1879343 TI - H beta 58, an insertional mutation affecting early postimplantation development of the mouse embryo. AB - The generation and analysis of insertional mutations affecting mouse embryogenesis provides a powerful method to identify new genes that function in early development. In this paper, we describe an insertional mutation that interferes with postimplantation mouse development beginning at the time of gastrulation. Embryos homozygous for the H beta 58 transgenic insertion developed normally through the early postimplantation, egg cylinder stage (day 6.5 of development). At the primitive streak stage (day 7.5), however, they began to display characteristic abnormalities, including a retardation in the growth of the embryonic ectoderm (the earliest identifiable defect), and in some cases abnormalities of the amnion and chorion. Homozygotes continued to develop for 2-3 more days, reaching the size of a normal 8.5 day embryo, and formed tissues representative of all three germ layers, including several differentiated cell types. The site of insertion was mapped, by a combination of cytogenetic and genetic methods, to chromosome 10, and it appeared to define a new genetic locus. The inserted transgene provided a probe to clone and characterize the mutant locus, as well as the corresponding wild-type locus. In addition to an insertion of 10-20 copies of the transgene, the mutant locus contained a deletion of 2-3 kb of DNA found at the wild-type locus, and possibly an insertion of mouse repetitive DNA. However, genomic sequences on both sides of the insertion site remained co-linear in the wild-type and mutant genomes, and no chromosomal abnormalities could be detected. Five single copy DNA probes spanning the insertion site were tested for their ability to hybridize to RNA from 8.5 day embryos; one of the probes (located within the region deleted from the mutant chromosome) hybridized to a 2.7 kb mRNA encoded at the H beta 58 locus, thus identifying a gene whose disruption appears to be responsible for the mutant phenotype. PMID- 1879344 TI - Tyrosine phosphorylation of p34cdc2 and p42 during meiotic maturation of Xenopus oocyte. Antagonistic action of okadaic acid and 6-DMAP. AB - The tyrosine phosphorylation/dephosphorylation of p34cdc2 was estimated by immunoblotting with antiphosphotyrosine antibody during meiotic maturation of Xenopus oocytes. At the time of germinal vesicle breakdown (GVBD), p34cdc2 is tyrosine dephosphorylated whereas a p42 protein, which might correspond to a MAP2 kinase, becomes tyrosine phosphorylated. No modification in the level of tyrosine phosphorylation of either proteins was noticed during the whole maturation process from GVBD until metaphase II. When added to prophase oocytes, 6-DMAP (6 dimethyl-aminopurine) blocks GVBC, M-phase-promoting factor (MPF) activation and H1-histone, kinase activation induced by either progesterone, MPF transfer or okadaic acid microinjection. In each case, the tyrosine dephosphorylation reaction of p34cdc2 is inhibited. In meiosis I oocytes (just after the initiation of GVBD), 6-DMAP provokes the rephosphorylation of p34cdc2 on tyrosine residue(s), inactivation of MPF and H1-histone kinase and re-entry of the cell into an interphase-like state. These processes are reversible by simply removing the agent. In contrast to the observations in prophase oocytes, okadaic acid is able to reverse the inhibitory effect of 6-DMAP in meiosis I oocytes on MPF and H1-histone kinase activities and to initiate dephosphorylation of p34cdc2 on tyrosyl residue(s) even in the presence of 6-DMAP. Altogether, our results show that 6-DMAP and okadaic acid antagonistically control in vivo the level of tyrosine phosphorylation of p34cdc2. PMID- 1879345 TI - Differential expression of two cadherins in Xenopus laevis. AB - Using a cadherin fraction from Xenopus tissue culture cells as an immunogen, two monoclonal antibodies were obtained that allowed the characterization of two distinct cadherins in the Xenopus embryo. The two cadherins differ in molecular weight, in their time of appearance during development and in their spatial pattern of expression. One of the antigens was identified as E-cadherin. It appears in the embryonic ectoderm during gastrulation when epidermal differentiation commences and it disappears from the neural plate area upon neural induction. The second antigen could not be allocated to any of the known cadherin subtypes and was termed U-cadherin. It is present in the egg and becomes deposited in newly formed inner cell membranes during cleavage, the outer apical membranes of the embryo remaining devoid of the cadherin throughout development. U-cadherin is found on membranes of all cells up to the late neurula stages. A conspicuous polarized expression of the antigen on the membranes of individual inner cells suggests its participation in the segregation of cell layers and organ anlagen. These findings are discussed in the context of current hypotheses on the role of cadherins in establishing the spatial structure of the embryo. PMID- 1879346 TI - XY follicle cells in the ovaries of XO/XY and XO/XY/XYY mosaic mice. AB - XO/XY and XO/XY/XYY mosaic hermaphrodites were generated from crosses involving BALB/cWt males. The distribution of Y-bearing cells in the gonads of these mice was studied by in situ hybridisation using the Y-specific probe pY353B. XY cells were found to contribute to all cell lineages of the ovary including follicle cells. The proportion of XY follicle cells was not significantly different from the XY contribution to other gonadal or non-gonadal cell lineages. However, this proportion was consistently low, all the hermaphrodites having a low XY contribution to the animal as a whole. Because the XO- and Y-bearing cell lineages are developmentally balanced, the XY follicle cells cannot have formed as a result of a 'mismatch' in which the Y-directed testis determination process is pre-empted by an early acting programme of ovarian development. These results are discussed with respect to the hypothesis that Tdy acts in the supporting cell lineage, the lineage from which Sertoli cells and follicle cells are believed to be derived. PMID- 1879347 TI - Plasma membrane localization of the Toll protein in the syncytial Drosophila embryo: importance of transmembrane signaling for dorsal-ventral pattern formation. AB - Formation of the Drosophila embryo's dorsal-ventral pattern requires the maternal product of the Toll gene. DNA sequence and genetic analyses together suggested that the Toll gene product is a transmembrane protein which communicates information from an extracytoplasmic compartment to the cytoplasm. Using antibodies as probes, we show that the Toll protein is a 135 x 10(3) Mr glycoprotein which is tightly associated with embryonic membranes. During the syncytial stage when dorsal-ventral polarity is established, the maternal Toll protein is associated with the plasma membrane around the entire embryo. During later embryonic stages, the Toll protein is expressed zygotically on many cell surfaces, possibly to promote cell adhesion. The plasma membrane localization of the Toll protein in the syncytial embryo suggests that transmembrane signaling from the extracellular perivitelline space to the cytoplasm is required for establishment of the embryonic dorsal-ventral pattern. PMID- 1879348 TI - The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation. AB - The segment polarity genes of Drosophila were initially defined as genes required for pattern formation within each embryonic segment. Some of these genes also function to establish the pattern of the adult cuticle. We have examined the role of the armadillo (arm) gene in this latter process. We confirmed and extended earlier findings that arm and the segment polarity gene wingless are very similar in their effects on embryonic development. We next discuss the role of arm in pattern formation in the imaginal discs, as determined by using a pupal lethal allele, by analyzing clones of arm mutant tissue in imaginal discs, and by using a transposon carrying arm to produce adults with a reduced level of arm. Together, these experiments established that arm is required for the development of all imaginal discs. The requirement for arm varies along the dorsal-ventral and proximal-distal axes. Cells that require the highest levels of arm are those that express the wingless gene. Further, animals with reduced arm levels have phenotypes that resemble those of weak alleles of wingless. We present a description of the patterns of arm protein accumulation in imaginal discs. Finally, we discuss the implications of these results for the role of arm and wingless in pattern formation. PMID- 1879349 TI - Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis. AB - In amphibian embryos, formation of the basic body plan depends on positional differences in the mesoderm. Although peptide growth factors involved in mesoderm induction have tentatively been identified, additional signals are required to generate pattern in this tissue. We have isolated a Xenopus cDNA for a Wnt-1 related gene, designated Xwnt-8, which is activated in response to mesoderm inducing growth factors. Xwnt-8 transcripts are transiently expressed, being most abundant during gastrulation at which time expression is confined primarily to ventral mesodermal cells. Embryos dorsoanteriorized by exposure to lithium exhibit greatly reduced levels of Xwnt-8 mRNA, supporting a correlation between Xwnt-8 expression and a ventral mesodermal cell fate. Surprisingly, ectopic expression of Xwnt-8 in embryos causes a dorsoanterior-enhanced phenotype. These findings suggest that Xwnt-8 may be a secondary signalling agent which is produced in response to mesoderm-inducing factors and is involved in the early steps of mesodermal patterning. PMID- 1879350 TI - Proliferation and differentiation potential of rat forebrain oligodendroglial progenitors both in vitro and in vivo. AB - We have followed the development of the O-2A progenitor cell from the neonatal rat forebrain, both in dissociated cell culture and in cryostat sections, using immunocytochemical techniques employing a panel of antibodies that recognise the cells at different stages of their development. This included the monoclonal antibody LB1, which binds to the surface ganglioside GD3 expressed on O-2A progenitor cells. In secondary cultures enriched for O-2A progenitors maintained in a serum-free chemically defined medium, a large proportion of the cells are primed to differentiate into oligodendroglia and go on to express the oligodendroglial specific surface glycolipid galactocerebroside (GC) and then the myelin proteins CNP and MBP. However, a significant proportion of immature bipolar GD3+ cells remained after 6 days in secondary culture. It appears that not all the O-2A progenitors in our cultures differentiate immediately and some cells remain in an undifferentiated state and divide to replenish progenitor numbers. We have also identified in our cultures a small apolar GD3- cell, which when isolated differentiated into a GD3+ bipolar O-2A progenitor cell. We have termed this cell type a preprogenitor. The differentiation of this cell type into O-2A progenitors may be the source of the immature GD3+ cells present at the later stages of our secondary cultures. The proliferative profile of the cultures was studied using 5'bromo-2-deoxyuridine (BrdU) incorporation as an index of mitosis. Only the immature, bipolar O-2A progenitors were seen to divide at any time in serum-free culture. Neither the more mature multipolar O-2A cells nor the oligodendroglia were seen to divide. The developmental profile of the O-2A cells in the rat forebrain in vivo showed a largely similar progression to that in culture, with a time lag of at least 6 days between GD3 expression and the onset of myelination. BrdU incorporation studies in vivo also showed that the GD3+ progenitor cell is mitotic whereas the GC(+)-expressing oligodendroglia is not. We have shown that there are several significant alterations in the timing of antigen expression in both O-2A progenitors and oligodendroglia in vitro compared to that seen in vivo. PMID- 1879351 TI - Complex regulation of TGF beta expression by retinoic acid in the vitamin A deficient rat. AB - We report the results of a histochemical study, using polyclonal antipeptide antibodies to the different TGF beta isoforms, which demonstrates that retinoic acid regulates the expression of TGF beta 2 in the vitamin A-deficient rat. Basal expression of TGF beta 2 diminished under conditions of vitamin A deficiency. Treatment with retinoic acid caused a rapid and transient induction of TGF beta 2 and TGF beta 3 in the epidermis, tracheobronchial and alveolar epithelium, and intestinal mucosa. Induction of TGF beta 1 expression was also observed in the epidermis. In contrast to these epithelia, expression of the three TGF beta isoforms increased in vaginal epithelium during vitamin A deficiency, and decreased following systemic administration of retinoic acid. Our results show for the first time the widespread regulation of TGF beta expression by retinoic acid in vivo, and suggest a possible mechanism by which retinoics regulate the functions of both normal and pre-neoplastic epithelia. PMID- 1879352 TI - The emergence of sense organs in the wing disc of Drosophila. AB - We have examined the origin of a set of precisely located sense organs in the notum and wing of Drosophila, in transformant flies where lacZ is expressed in the progenitor cells of the sense organs (the sensory mother cells) and in their progeny. Here we describe the temporal pattern of appearance and divisions of the sensory mother cells that will form the eleven macrochaetes and the two trichoid sensilla of the notum, and five campaniform sensilla on the wing blade. The complete pattern of sensory mother cells develops in a strict sequence that extends over most of the third larval instar and the first 10 h after puparium formation. The delay between the onset of lacZ expression and the first differentiative division ranges from 30 h, in the case of the earliest mother cells, to 2 h for the latest mother cells. The first division shows a preferential orientation which is also specific for each sensory mother cell. Up to this stage, there is no marked difference between the three types of mechanosensory organs. PMID- 1879353 TI - Timing of paternal Pgk-1 expression in embryos of transgenic mice. AB - In mouse development, the paternal allele of the X-linked gene Pgk-1 initiates expression on day 6, two days later than the maternal allele, which is activated on day 4. The different timing of expression of the maternal and paternal alleles may be determined by (i) imprinting of the chromosome region in which the gene resides, but not aimed specifically at the Pgk-1 gene; (ii) gene specific imprinting, acting on Pgk-1 irrespective of the chromosomal localization of the gene; (iii) an interplay between embryo cell differentiation, timing of X inactivation and Pgk-1 expression, without the involvement of imprinting at the Pgk-1 locus itself (Fundele R., Illmensee, K., Jagerbauer, E. M., Fehlau, M. and Krietsch, W. K. (1987) Differentiation 35, 31-36). Our findings in transgenic mouse lines, carrying Pgk-1 on autosomes, indicate the importance of the X chromosomal location for the delayed expression of the paternal Pgk-1 allele, and are in agreement with the first of the explanations listed above. We propose that the late activation of the paternal Pgk-1 locus is a consequence of imprinting targeted at, and centered around, the X chromosome controlling element. PMID- 1879354 TI - Mis-regulating segmentation gene expression in Drosophila. AB - We have used the hunchback (hb) gap-gene promoter to drive ectopic expression of the pair-rule genes fushi tarazu (ftz), even-skipped (eve) and hairy (h). Unexpectedly, flies transformed with such constructs are viable, despite spatial and temporal mis-regulation of pair-rule expression caused by the fusion genes. We show that fusion gene expression is transcriptionally regulated, such that ectopic expression is suppressed when pattern is established, and present evidence indicating that interstripe hb-ftz expression is repressed by eve. These results are considered in terms of redundant control of pair-rule gene striping. We also discuss the potential dangers of using mis-regulated gene expression to analyse normal function. PMID- 1879355 TI - Survival of XO mouse fetuses: effect of parental origin of the X chromosome or uterine environment? AB - Using a recombinant product from the structurally abnormal Y chromosome, Y*, female mice with a single X of either maternal or paternal origin were generated. The two types of females were produced on the same genetic background and differ only in the origin of the X chromosome. Hence it has been possible to assess the effect of parental origin of the X on survival of females with a single X chromosome. A highly significant prenatal loss of females with a single X of paternal origin, but no comparable loss of females with a single X of maternal origin was observed. The reduced viability of females with a paternally derived X could be mediated by the parental origin of the X (i.e. X chromosome imprinting) or alternatively, since the mothers of females with a single paternally derived X have only a single X chromosome, the effect could be mediated by the genotype of the mother (i.e. maternal uterine effect). PMID- 1879356 TI - Deep cytoplasmic rearrangements during early development in Xenopus laevis. AB - The egg of the frog Xenopus is cylindrically symmetrical about its animal-vegetal axis before fertilization. Midway through the first cell cycle, the yolky subcortical cytoplasm rotates 30 degrees relative to the cortex and plasma membrane, usually toward the side of the sperm entry point. Dorsal embryonic structures always develop on the side away from which the cytoplasm moves. Details of the deep cytoplasmic movements associated with the cortical rotation were studied in eggs vitally stained during oogenesis with a yolk platelet specific fluorescent dye. During the first cell cycle, eggs labelled in this way develop a complicated swirl of cytoplasm in the animal hemisphere. This pattern is most prominent on the side away from which the vegetal yolk moves, and thus correlates in position with the prospective dorsal side of the embryo. Although the pattern is initially most evident near the egg's equator or marginal zone, extensive rearrangements associated with cleavage furrowing (cytoplasmic ingression) relocate portions of the swirl to vegetal blastomeres on the prospective dorsal side. PMID- 1879357 TI - Vital dye labelling demonstrates a sacral neural crest contribution to the enteric nervous system of chick and mouse embryos. AB - We have used the vital dye, DiI, to analyze the contribution of sacral neural crest cells to the enteric nervous system in chick and mouse embryos. In order to label premigratory sacral neural crest cells selectively, DiI was injected into the lumen of the neural tube at the level of the hindlimb. In chick embryos, DiI injections made prior to stage 19 resulted in labelled cells in the gut, which had emerged from the neural tube adjacent to somites 29-37. In mouse embryos, neural crest cells emigrated from the sacral neural tube between E9 and E9.5. In both chick and mouse embryos, DiI-labelled cells were observed in the rostral half of the somitic sclerotome, around the dorsal aorta, in the mesentery surrounding the gut, as well as within the epithelium of the gut. Mouse embryos, however, contained consistently fewer labelled cells than chick embryos. DiI labelled cells first were observed in the rostral and dorsal portion of the gut. Paralleling the maturation of the embryo, there was a rostral-to-caudal sequence in which neural crest cells populated the gut at the sacral level. In addition, neural crest cells appeared within the gut in a dorsal-to-ventral sequence, suggesting that the cells entered the gut dorsally and moved progressively ventrally. The present results resolve a long-standing discrepancy in the literature by demonstrating that sacral neural crest cells in both the chick and mouse contribute to the enteric nervous system in the postumbilical gut. PMID- 1879358 TI - Origins and patterning of avian outflow tract endocardium. AB - Outflow tract endocardium links the atrioventricular lining, which develops from cardiogenic plate mesoderm, with aortic arches, whose lining forms collectively from splanchnopleuric endothelial channels, local endothelial vesicles, and invasive angioblasts. At two discrete sites, outflow tract endocardial cells participate in morphogenetic events not within the repertoire of neighboring endocardium: they form mesenchymal precursors of endocardial cushions. The objectives of this research were to document the history of outflow tract endocardium in the avian embryo immediately prior to development of the heart, and to ascertain which, if any, aspects of this history are necessary to acquire cushion-forming potential. Paraxial and lateral mesodermal tissues from between somitomere 3 (midbrain level) and somite 5 were grafted from quail into chick embryos at 3-10 somite stages and, after 2-5 days incubation, survivors were fixed and sectioned. Tissues were stained with the Feulgen reaction to visualize the quail nuclear marker or with antibodies (monoclonal QH1 or polyclonals) that recognize quail but not chick cells. Many quail endothelial cells lose the characteristic nuclear heterochromatin marker, but they retain the species specific epitope recognized by these antibodies. Precursors of outflow tract but not atrioventricular endocardium are present in cephalic paraxial and lateral mesoderm, with their greatest concentration at the level of the otic placode. Furthermore, the ventral movement of individual angiogenic cells is a normal antecedent to outflow tract formation. Cardiac myocytes were never derived from grafted head mesoderm. Thus, unlike the atrioventricular regions of the heart, outflow tract endocardial and myocardial precursors do not share a congruent embryonic history. The results of heterotopic transplantation, in which trunk paraxial or lateral mesoderm was grafted into the head, were identical, including the formation of cushion mesenchyme. This means that cushion positioning and inductive influences must operate locally within the developing heart tubes. PMID- 1879359 TI - The restricted spatial and temporal expression of a nervous-system-specific antigen involved in axon outgrowth during development of the grasshopper. AB - To identify molecules important for pathfinding by growing axons, monoclonal antibodies (mAb) have been generated against embryonic grasshopper tissue. One mAb, 2B2, shows labeling exclusively in the nervous system. It recognizes a surface epitope on neuronal growth cones, filopodia and axons in the central nervous system (CNS). Initially, the antigen is expressed on all processes of the CNS; after 70% of embryonic development, localization of the 2B2 mAb is restricted to a small subset of axon tracts within the ganglia. Immunoprecipitation from embryonic membrane extracts with the 2B2 mAb reveals a unique band of 160 x 10(3) Mr. Functional studies with the 2B2 mAb demonstrate that the antigen is important in growth cone-axon interactions during process outgrowth. Growth cones that extend along axonal substrata are either blocked in growth or grow along an aberrant pathway when embryos are cultured in the presence of the 2B2 mAb. However, pioneer neurons that extend processes on non neuronal substrata grow normally. PMID- 1879360 TI - Retarded nuclear migration in Drosophila embryos with aberrant F-actin reorganization caused by maternal mutations and by cytochalasin treatment. AB - Three X-linked mutations of Drosophila melanogaster, gs(1)N26, gs(1)N441 and paralog, had a common maternal-effect phenotype. Mutant embryos show reduced egg contraction that normally occurs at an early cleavage stage in wild-type embryos. In addition, the mutants exhibited retarded nuclear migration while synchronous nuclear divisions were unaffected. The retarded migration causes nuclei to remain in the anterior part of the embryo retaining their spherical distribution even in a late cleavage stage. This consequently results in an extreme delay in nuclear arrival in the posterior periplasm. A mutant phenocopy was induced in wild-type embryos that were treated with cytochalasin B or D at a very early cleavage stage. Remarkable differences were noticed in the organization of cortical F actin between the mutants and the wild type throughout the cleavage stage: obvious F-actin aggregates were dispersed in the cortex of mutant embryos, in contrast to the wild type where the cortical F-actin layer was smooth and underlying F-actin aggregates were smaller than those in the mutants; the transition of the distribution pattern of F-actin in the yolk mass, from the centralized to the fragmented type, occurred later in the mutants than in wild type. The results suggest that these mutations affect the mechanism underlying establishment and transition of F-actin organization required for normal egg contraction and nuclear migration in the cleavage embryos. PMID- 1879361 TI - Control of cell fate in the tail region of C. elegans by the gene egl-5. AB - The tail region of C. elegans contains a number of blast cell and neuron types that either are found only in the tail, or are different from more anterior homologues. In egl-5 mutants, the fates of many of these tail cells are abnormal or transformed to those of anterior homologues. The affected cells are related only by position and not by ancestry. egl-5 is also required for normal development of the somatic gonad and sex muscles in males. The function of egl-5 in all these tissues is cell autonomous. By genetic mapping, egl-5 lies very close to mab-5, a gene with an analogous role in the immediately anterior body region. egl-5 and mab-5 may constitute a 'mini-cluster' of regional determination genes, similar to those described in other animal phyla. PMID- 1879362 TI - The expression of NG2 proteoglycan in the developing rat limb. AB - NG2 is a chondroitin sulfate proteoglycan previously found to be expressed by glial progenitor cells of the O2A lineage. We have examined the expression of NG2 in the developing rat limb by immunohistochemistry and northern blot analysis. Staining of embryonic day 14 (E14) rat limb bud sections with polyclonal and monoclonal anti-NG2 antibodies reveals reactivity in the precartilaginous mesenchymal condensation. The staining intensity increases with the differentiation of chondrocytes until E16. NG2 staining is not detected in the mature hypertrophic chondrocytes of E17 and postnatal day 3 (P3) limbs even after treatment of the sections with hyaluronidase or collagenase. Immuno precipitations with anti-NG2 antibody using 125I-labeled limb cells in culture showed a 400 to 800 x 10(3) Mr proteoglycan species with a core protein size of 300 x 10(3) Mr, comparable to NG2 from O2A cells and neural cell lines. Northern blot analysis reveals the expression of an 8.9 kb mRNA in E16 limbs and at a lower level in P1 cartilage. The northern blot analyses also show that NG2 is distinct from the large aggregating proteoglycan of the cartilage. Our results indicate that in the developing limb cartilage, as in the differentiating oligodendrocytes, NG2 is present on immature cells in the process of differentiating, but its expression is downregulated as terminal differentiation of chondrocytes takes place. PMID- 1879363 TI - Expression of the mouse alpha 1(II) collagen gene is not restricted to cartilage during development. AB - The mouse alpha 1(II) collagen gene has been isolated and a 5' portion of the gene which has low homology to other collagen genes was used to study the pattern of expression during mouse embryogenesis. In situ hybridization studies show that in the mouse, like the chick, alpha 1(II) collagen is expressed in chondrogenic tissues in advance of chondrocyte differentiation. The gene is expressed early in embryogenesis at 9.5 days both in the cranial mesenchyme destined for the chondrocranium, and the sclerotome of the somites, and at 12.5 days in the primordia of the hyoid and the laryngeal cartilage. Type II collagen gene transcripts were found in all the chondrogenic tissues of the axial and appendicular skeleton until the onset of endochondral ossification. Expression of alpha 1(II) collagen mRNA was also observed in non-chondrogenic tissues such as the notochord which may be responsible for inducing chondrogenesis in somitic mesoderm, neural retina, the corneal and conjunctival epithelia and sclera of the developing eye. Expression in the tail tendon was late, at 16.5-18.5 days. Transient expression was also found in the heart at 9.5-12.5 days, the epidermis at 10.5-14.5 days, the calvarial mesenchyme at 12.5-16.5 days, the inner ear at 14.5 days and the fetal brain from 9.5-14.5 days. Within the neural tube, alpha 1(II) collagen mRNA was localized in the proliferative ventricular cells of the forebrain and midbrain of 9.5- to 10.5-day embryos. Subsequently, transcription of the alpha 1(II) collagen gene was confined to restricted areas of the rhombencephalic basal plate, the ventricular layer of the hindbrain and the cervical spinal cord. These examples of expression of the type II collagen gene in the developing nervous system seem to suggest that active transcription of this gene might be associated with early stages of neuroblast differentiation. Type II collagen may therefore have additional roles in development unrelated to chondrogenesis. PMID- 1879364 TI - The transient expression of type II collagen at tissue interfaces during mammalian craniofacial development. AB - Using immunocytochemical techniques, the spatiotemporal distribution of the major collagen isoform of cartilage, type II collagen, has been investigated during early craniofacial development in the mouse embryo. Early and transient expression was associated with the otic and optic vesicles, the ventrolateral surfaces of the developing brain, olfactory conchi, endocardial and mesocardial tissues, the lateral and basal surfaces of the pharyngeal endoderm and beneath the ectoderm of the branchial arches. A number of these locations are sites of epithelial-mesenchymal tissue interaction believed to generate the component parts of the chondrocranium; here, type II collagen appears transiently in advance of overt chondrogenesis in the mesenchyme. At such sites, immunofluorescence is typically localised along the basal surface of the epithelial partner, with the strongest reaction detected between the basal aspects of the otic and rhombencephalic epithelia. Immunoelectron microscopy, using pre-embedding immunostaining and a protein G-gold technique, reveals that the type II collagen is adjacent to, but not integral with, the basal laminae. Gold particles are clearly associated with 10-15 nm fibrils of the extracellular matrix in the reticulate lamina region. The pattern of type II collagen expression in the mouse closely correlates with that demonstrated previously in the quail, indicating a high degree of phylogenetic conservation between these two vertebrate species. These findings are consistent with the hypothesis that the pattern of epithelial secretion of type II collagen, or a coexpressed matrix molecule, constitutes a morphogenetic signal, realised as a matrix-mediated tissue interaction, and specifying the form of the vertebrate chondrocranium. Three-dimensional reconstruction of early type II collagen distribution, and of the subsequent chondrocranial cartilages, reveals that chondrocranial form can be derived from a 'pre-pattern' of epithelially derived type II collagen expressed at epithelial-mesenchymal tissue interfaces. PMID- 1879365 TI - A novel retrovirally induced embryonic lethal mutation in the mouse: assessment of the developmental fate of embryonic stem cells homozygous for the 413.d proviral integration. AB - A genetic screen of transgenic mouse strains, carrying multiple copies of an MPSV neo retroviral vector, has led to the identification of a recessive embryonic lethal mutation, termed 413.d. This mutation is associated with a single proviral insertion and when homozygous, results in the failure of the early postimplantation embryo at the gastrulation stage of development. Embryonic stem cell lines (ES cells) were derived from 413.d intercross embryos. Genotyping, with respect to the 413.d integration site, identified wild-type, heterozygous and homozygous ES cell lines. The differentiation abilities and developmental potential of the ES cell lines were assessed using a number of in vitro and in vivo assays. Results indicate that the ES cell lines, regardless of genotype, are pluripotent and can give rise to tissue and cell types derived from all three germ layers. Furthermore, analysis of midgestation conceptuses (10.5 p.c.) and adult chimeras generated by injecting mutant ES cells into host blastocysts, provides strong evidence that the mutant cells can contribute to all extraembryonic tissues and somatic tissues, as well as to functional germ cells. These results indicate that the homozygous mutant cells can be effectively 'rescued' by the presence of wild-type cells in a carrier embryo. PMID- 1879367 TI - Positional cues governing cell migration in leech neurogenesis. AB - The stereotyped distribution of identified neurons and glial cells in the leech nervous system is the product of stereotyped cell migrations and rearrangements during embryogenesis. To examine the dependence of long-distance cell migrations on positional cues provided by other tissues, embryos of Theromyzon rude were examined for the effects of selective ablation of various embryonic cell lines on the migration and final distribution of neural and glial precursor cells descended from the bilaterally paired ectodermal cell lines designated q bandlets. The results suggest that neither the commitment of q-bandlet cells to migrate nor the general lateral-to-medial direction of their migration depend on interactions with any other cell line. However, the ability of the migrating cells to follow their normal pathways and to find their normal destinations does depend on interactions with cells of the mesodermal cell line, which appears to provide positional cues that specify the migration pathways. PMID- 1879368 TI - Schmidt syndrome due to idiopathic accessory nerve paralysis. AB - A patient with Schmidt syndrome due to idiopathic accessory neuropathy has had paralysis of soft palate and larynx as well as trapezius and sternocleidomastoid muscles, reflecting involvement of cranial and spinal roots, respectively. In addition to vocal cord paralysis on the laryngoscopy, videofluoroscopy confirmed diminished mobility of the soft palate. Electrodiagnosis showed accessory neuropathy at the proximal segment. Furthermore, the accessory nerve innervated not only upper but also middle and lower portions of the trapezius muscles. PMID- 1879366 TI - The snail gene required for mesoderm formation in Drosophila is expressed dynamically in derivatives of all three germ layers. AB - The zygotic effect gene snail (sna) encodes a zinc-finger protein required for mesoderm formation in Drosophila embryos. By in situ analysis, sna transcripts are first detected at syncytial blastoderm and persist until very late stages of embryogenesis. Expression of sna is transient and is observed in tissues derived from all three germ layers. Prior to germband elongation, sna RNA accumulation is consistent with its genetically determined role in mesoderm formation. Starting at germband elongation, a second phase of sna expression appears to be initiated, characterized by a highly dynamic accumulation of transcripts in the developing central and peripheral nervous systems. Translation of sna RNA is apparently delayed as the sna protein is not detected before the onset of gastrulation. Its regional distribution generally correlates with that of sna transcripts. The complex pattern of sna expression strongly suggests that the function of the gene is not restricted to mesoderm formation. PMID- 1879369 TI - Biocybernetic investigations of pursuit and posture motor control--a strategy for a detailed characterization of movement disorders in brain-damaged children. AB - By means of a biocybernetic approach the pursuit and posture motor control of brain-damaged children with spastic hemiparesis and disturbed motor coordination of mild extent were investigated. The postural motor control system was loaded by pseudostochastic binary torque sequences applied to the wrist. The dynamics of this system were characterized on the basis of the parameters forearm displacement as well as surface-EMG of M. Biceps and Triceps (calculations of weight functions). The pursuit motor control was analyzed by a pursuit tracking method. By this way the motor capacity for fine and rough motor coordination, motor rhythm, motor adaptation, the maximal speed of movements and motor reaction time could be tested. Considering these results a characterization of movement control on different levels of motor regulation was possible (dynamics of muscular, spinal, and supraspinal components of motor control). PMID- 1879370 TI - Abnormal brainstem evoked potentials in diabetes mellitus. Evoked potential testings and magnetic resonance imaging. AB - Brainstem auditory evoked potentials (BAEPs) and median nerve somatosensory evoked potentials (MN-SEPs) were measured in 53 diabetic patients. Magnetic resonance imaging (MRI) was performed 12 patients with abnormal BAEPs and/or MN SEPs in order to confirm the existence of lesions in the central nervous system. Twenty-six percent of the diabetic patients had abnormal BAEPs and three had a prolongation of the central conduction time in the MN-SEPs. MRI findings of ten of the 12 patients with abnormal BAEPs or MN-SEPs showed multiple small lesions in the pons, thalamus, and centrum semiovale etc. Two of them showed small lesion in the pontine basis which could induce prolonged interpeak latencies of BAEPs. Our MRI study might suggest that abnormal brainstem evoked potentials in diabetic patients were induced by diabetic macroangiopathy or microangiopathy. PMID- 1879371 TI - Proceedings of the fourth conference on the adrenal cortex. June 17-19, 1990, Atlanta, Georgia. PMID- 1879372 TI - Regulation of steroid hydroxylases in normal and SV40 T antigen-transfected bovine adrenocortical cells in long-term culture. AB - Over long periods of growth in culture, bovine adrenocortical cells lose the ability to express the steroid hydroxylase genes. For 17 alpha-hydroxylase, cells show a stochastic pattern of phenotypic switching from a state in which they express this gene in response to cyclic AMP to a state in which the gene is no longer inducible. Introducing SV40 T antigen into bovine adrenocortical cells greatly increases their replicative potential; steroid hydroxylase expression in these clones resembles that of the precursor cells before transfection. The other steroid hydroxylases (21-hydroxylase and 11 beta-hydroxylase) appear to undergo phenotypic switching like 17 alpha-hydroxylase. The loss of expression of these genes appears to be more rapid, but there are differences in the requirements of 21-hydroxylase and 11 beta-hydroxylase versus 17 alpha-hydroxylase for induction by cyclic AMP; additionally, growth of cells in extracellular matrix Matrigel was required for expression of 21-hydroxylase and 11 beta-hydroxylase in long-term cultures of either normal or SV40 T antigen-transfected cells. Understanding the molecular basis for the phenotypic switching of steroid hydroxylases that occurs in bovine adrenocortical cells may elucidate mechanisms for cellular senescence and for maintenance of tissue-specific functions during long-term growth in culture. PMID- 1879373 TI - Synthesis of aldosterone by mitochondria and homogeneous 11 beta-hydroxylase from beef and pig. AB - It was found that homogeneous 11 beta-hydroxylase from bovine and porcine adrenals catalyzes the conversion of DOC to aldosterone. Mitochondria from both glomerulosa and fasciculata also convert DOC to aldosterone but glomerulosa is much more active than fasciculata. Cholate extracts of mitochondria from the two zones were equally active in converting DOC to aldosterone. Moreover all the enzyme activities of 11 beta-hydroxylase (including 18-hydroxylation and aldehyde synthetase) were precipitated by a polyclonal antibody raised in rabbit against the pure 11 beta-hydroxylase. It is concluded that in beef and pig a single adrenocortical 11 beta-hydroxylase is responsible for the synthesis of aldosterone. To determine the influence of the mitochondrial membrane from glomerulosa and fasciculata on the activities of 11 beta-hydroxylase we examined the activities of rotenone-insensitive reductase enzymes in mitochondria from the two zones. Semidehydroxyascorbate reductase and NADH-cytochrome C reductase activities are considerably more active in glomerulosa than in fasciculata mitochondria. Moreover ascorbate plus NADH (but not ascorbate alone) greatly increases the ability of malate and NADPH to support synthesis of aldosterone without affecting 11 beta- or 18-hydroxylations in mitochondria. It is proposed that maximal synthesis of aldosterone by adrenocortical mitochondria requires in addition to the usual electron transport system (NADPH- greater than ADR- greater than ADX- 11 beta-OHase) an auxilliary system in the outer mitochondrial membrane: NADH- greater than Fp- greater than cyt b- greater than semidehydroascorbate reductase. PMID- 1879374 TI - Molecular nature of aldosterone synthase, a member of cytochrome P-450(11 beta) family. AB - The molecular nature of the aldosterone synthesizing enzymes of cattle and rat is discussed. In bovine adrenal cortex, one molecular species of cytochrome P-450(11 beta) catalyzes aldosterone synthesis as well as 11 beta-hydroxylation. The intactness of the mitochondrial membrane surrounding P-450(11 beta) in the zonae fasciculata-reticularis is essential to keep the aldosterone synthesizing activity of the cytochrome in these zones latent. In rat adrenal cortex, two distinct molecules belonging to a P-450(11 beta) family exist. One is 11 beta hydroxylase, and the other aldosterone synthase. PMID- 1879375 TI - Two forms of cytochrome P-450(11 beta) in rat zona glomerulosa cells: a short review. AB - Aldosterone, the major mineralocorticoid hormone, is produced exclusively in the zona glomerulosa of the mammalian adrenal cortex. In the rat species, this zonal specificity of aldosterone biosynthesis appears to be due mainly to the existence of a second form of cytochrome P-450(11 beta), which differs from the major form of the enzyme (molecular weight 51,000) by (1) a lower molecular weight (49,000), (2) a broader range of catalytic activities, which include corticosterone methyl oxidation 1 and 2, (3) an exclusive occurrence in the zona glomerulosa, and (4) a crucial dependence on sodium and potassium intake. The 49K form of the enzyme can be induced by potassium ions in vivo (potassium repletion of potassium-deficient rats) or in vitro (primary cell culture). The biosynthesis of this protein is controlled most likely at the level of transcription. According to indirect evidence, ACTH induces only the 51K form of the enzyme in vitro. Prolonged treatment of rats with a high dose of ACTH has a repressive effect on the 49K form of the enzyme. PMID- 1879376 TI - Succinate stimulation of isocitrate supported deoxycorticosterone metabolism in rat adrenal mitochondria by a synergistic mechanism. AB - The relative effectiveness of succinate and isocitrate in supplying NADPH for cholesterol and deoxycorticosterone (DOC) metabolism by rat adrenal mitochondria has been investigated. As previously seen for cholesterol metabolism, isocitrate supported DOC metabolism at a higher rate than succinate. Maximal rates of DOC metabolism, however, required 10 times more precursor (10mM) than cholesterol metabolism. Addition of DOC to mitochondria inhibited cholesterol metabolism, indicating competition for NADPH between these pathways. Coaddition of these reducing precursors resulted in a substantially greater than additive rate of DOC hydroxylation, but not cholesterol metabolism. The synergistic effect was seen with both 11 beta- and 18 hydroxylation. For both precursors, the synergism was maximal upon addition of only 1 mM of the second precursor. The synergistic effect was far more resistant to added KCN and malonate than succinate supported DOC metabolism, and neither inhibitor affected isocitrate supported DOC metabolism. These results suggest that while cytochromes P450scc and P450(11 beta) use a common supply of NADPH generated by each precursor, there is a pool of NADPH that is only effectively synthesised upon coaddition of precursors and only utilised by cytochrome P450(11 beta). This second NADPH pool may be produced in response to potentiated isocitrate dehydrogenase activity or activation of a different NADPH generating system. PMID- 1879377 TI - On the solvent accessibility of substrate binding site of cytochrome P450C-21 in bovine adrenocortical microsomes. AB - The present study offers evidence indicating that acrylamide a polar molecule inhibits substrate-binding to P450C-21 in a competitive manner and quenches tryptophanyl fluorescence in bovine adrenocortical microsomes, similar to that in the purified lipid-free enzyme. Resolution of tryptophanyl fluorescence of the microsomes revealed an acrylamide quenching constant (K2 = 9.9M, is the association constant for the quencher-fluorophore complex) which was similar to the reciprocal of its inhibition constant (1/Kj = Ka = 8.3 +- 0.9M) for substrate binding. The substrate inhibited the fluorescence quenching by acrylamide which was in accordance with partial competition. In addition the substrate dissociation, acrylamide inhibition and fluorescence quenching constants and tryptophanyl fluorescence maximum (340-342nm) were essentially the same in the microsomes and the purified enzyme. These results suggest that, similar to that in the purified enzyme, a tryptophan in a polar environment in the membrane-bound P450, may serve as a reporter group for the substrate binding site and the site in the membrane-bound enzyme, is accessible to the substrate in aqueous phase. PMID- 1879378 TI - Transforming growth factor beta 1: an autocrine regulator of adrenocortical steroidogenesis. AB - Transforming growth factor beta 1 (TGF beta 1) is a member of a large family of structurally related regulatory polypeptides which comprises both functionally similar (TGF beta 1, TGF beta 2, TGF beta 3, TGF beta 4 and TGF beta 5) and functionally distinct proteins. In the past few years, TGF beta 1 has emerged as a multifunctional protein. One of its remarkable properties is its capacity to negatively modulate the differentiated, steroidogenic adrenocortical functions. We present here a review of the results from our recent work related to the effects of TGF beta 1 on bovine adrenocortical cell (zona fasciculata reticularis) functions. We identified the steroid 17 alpha-hydroxylase (P-450 17 alpha) biosynthetic enzyme and the angiotensin II receptor as major targets whose expression are negatively regulated by TGF beta 1 in these cells. We characterized TGF beta 1 receptors at the surface of adrenocortical cells (mainly type I and type III receptors) and observed that their number is increased under ACTH treatment. Furthermore, we could detect the presence of immunoreactive TGF beta 1 in the bovine adrenal cortex whereas it was undetectable in the adrenal medulla and in the capsule. We also observed that adrenocortical cells secrete TGF beta 1 under a latent form together with large amounts of alpha 2 macroglobulin, a protease inhibitor known to be implied in the latency of TGF beta in serum. Taken together, these observations led us to a working hypothesis, proposing TGF beta 1 as an autocrine and/or paracrine regulator of adrenocortical steroidogenic functions. This concept points out the physiological activation of the latent TGF beta 1 complex as the important limiting step controlling its action in the adrenal cortex. PMID- 1879379 TI - Inhibition of mitochondrial cholesterol side-chain cleavage by structural analogs of cholesterol sulfate. AB - Cholesterol sulfate inhibits cholesterol side-chain cleavage in adrenal mitochondria. In this study, analogs of cholesterol sulfate were evaluated for their ability to inhibit steroidogenesis. Structural requirements for inhibitory activity included a planar A-B ring junction, an intact side chain, and a 3 beta ester group containing a single negative charge. This structural specificity argues against cholesterol sulfate acting solely as a membrane perturbing agent or a detergent, and also differs in some features from the specificity for binding to cytochrome P-450scc. PMID- 1879380 TI - Chemical synthesis, initial conformational studies, and activity of rat steroidogenesis activator peptide and a truncated analog. AB - A 30-residue peptide corresponding to the amino acid sequence of steroidogenesis activator peptide (SAP) from rat Leydig tumor cells has been synthesized by the solid-phase method using Boc protection. SAP is the putative cycloheximide sensitive, cAMP-regulated mediator of ACTH-stimulated conversion of cholesterol to pregnenolone in adrenal cortex. N alpha-acetyl-SAP(11-30), an NH2-terminally truncated steroidogenesis activator peptide analog that is missing the most hydrophobic portion of SAP, was also prepared. In addition to these two peptides, N alpha-acetyl-(Cys0)SAP was synthesized in both non-radiolabeled and tritiated forms for coupling to carrier proteins for use as an immunogen to raise anti-SAP antibodies. Chain elongation during synthesis of SAP on PAM resin proceeded with an average coupling yield of 99.3% as determined by quantitative ninhydrin tests. After HF cleavage at -7 degrees, the crude products were purified by semi preparative HPLC. Peptides were analyzed by analytical HPLC, amino acid analysis, tryptic peptide mapping, and by UV and CD spectroscopy. As determined by CD spectra, SAP showed little evidence of preferred structure either in aqueous solution in the presence of divalent cations or in micelles of reduced Triton X 100 in the absence or presence of either cholesterol or phosphatidylcholine. SAP, in conjunction with GTP, enhanced side chain cleavage activity in isolated adrenal mitochondria. PMID- 1879381 TI - Salt sensitive human hypertension. AB - Heterogeneity exists among humans in the responses of blood pressure to alterations in sodium and extracellular fluid volume status. A variety of approaches have been utilized to characterize sodium responsivity of blood pressure including rapid volume expansion and contraction and dietary sodium manipulation. Studies conducted in our laboratories over the past 15 years have enabled us to examine salt sensitivity of blood pressure in different ways and to characterize this phenomenon as well as to define neurohumoral, demographic and genetic factors associated with it in normotensive and hypertensive humans. PMID- 1879382 TI - Clinical, biochemical and molecular aspects of 17-hydroxylase deficiency. PMID- 1879384 TI - Intestinal absorption and losses of copper measured using 65Cu in zinc-deprived men. AB - The absorption and intestinal losses of endogenous Cu in response to a low Zn diet were studied in five young male subjects using stable 65Cu as an oral tracer. The subjects received a semi-purified formula diet providing 85 mumol (5.6 mg) Zn/d during 15-day baseline and repletion phases and 12 mumol (0.8 mg) Zn/d during an intervening period of 25 days. Thirty-eight mumol (2.4 mg) Cu/d was provided throughout the study. In four of the subjects, the mean +/- SEM luminal disappearance of 65Cu was 37 +/- 4 per cent during the baseline phase and was unaffected by Zn deprivation (32 +/- 7 per cent) or repletion (30 +/- 7 per cent) as were intestinal losses of endogenous Cu [7 +/- 4, 8 +/- 3, 8 +/- 3 mumol/d (0.4 +/- 0.1, 0.5 +/- 0.1, 0.5 +/- 0.1 mg/d) during baseline, Zn deprivation and Zn repletion phases, respectively]. In a fifth subject, who had some evidence of a resolving alcohol-induced hepatitis, the luminal disappearance of 65Cu was 31, 44 and 42 per cent and the intestinal losses of endogenous Cu 11, 2 and 6 mumol/d (0.7, 0.1 and 0.4 mg/d) during the baseline, Zn deprivation and Zn repletion phases respectively. Plasma Cu concentrations, however, fell throughout the study in all the subjects, despite consistently positive Cu balances. There may be subtle effects of a low dietary intake of Zn on Cu metabolism which were not revealed by the methods used in this study. PMID- 1879383 TI - Defects in cortisol metabolism causing low-renin hypertension. AB - Deficiency of steroid 11 beta-hydroxylase, which is a mitochondrial cytochrome P450 required for cortisol and aldosterone synthesis, causes hypertension as well as virilization. In addition, abnormal regulation of this enzyme or a closely related isozyme may be involved in an autosomal dominant form of inherited hypertension, dexamethasone-suppressible hyperaldosteronism. An enzyme that catalyzes the interconversion of cortisol and cortisone, 11 beta-hydroxysteroid dehydrogenase, may be defective in an autosomal recessive form of hypertension termed apparent mineralocorticoid excess. The molecular bases of these forms of hypertension will be elucidated by identifying mutations in the 11 beta hydroxylase and 11 beta-hydroxysteroid dehydrogenase genes and expressing normal and mutagenized enzymes in cultured cells. PMID- 1879385 TI - Iron status in non-pregnant women of child-bearing age living at Greater Buenos Aires. AB - This survey was conducted in Greater Buenos Aires to assess the iron nutritional status of non-pregnant women of child-bearing age. One hundred and eighty-four subjects aged 16-44 years were studied. The prevalence of anaemia (haemoglobin concentration less than 120 g/l) was 25.8 per cent. According to the multiple criteria approach, 21.6 per cent of women presented two or three abnormal values of iron status indicators (free erythrocyte protoporphyrin, serum ferritin and/or mean corpuscular volume). Prevalences of anaemia were 19.2 per cent, 51.8 per cent and 100 per cent in women with 0-1, 2 or 3 indicators in the abnormal range, respectively. The haemoglobin shift analysis showed a prevalence of anaemia of 19.5 per cent. Frequency distribution of iron stores was calculated as described by Cook & Finch, with slight modifications; median value of iron stores was estimated at 180 mg iron. Depletion of iron stores was significantly associated with the socio-economic status, prevalences being 5.3 per cent, 34.2 per cent and 43.2 per cent for the high, middle and low socioeconomic groups, respectively. PMID- 1879386 TI - Is colonic fermentation minimized by increasing meal frequency? AB - It has been suggested that, although increasing meal frequency has metabolic advantages in terms of carbohydrate and lipid metabolism, the efficiency of small intestinal absorption may be enhanced, thus reducing the extent of colonic fermentation. Since this may be undesirable, we have tested whether increasing meal frequency reduces the amount of carbohydrate fermented into the colon. Accordingly, seven healthy male volunteers took, in random order, two identical 2 week metabolic diets divided into either seventeen or three meals daily. On day 13 of each period measurements were made throughout the day of breath H2 and serum acetate, as markers of colonic fermentation. Mean levels of both breath H2 and acetate were similar on both diets, being lower on nibbling by 3.2 +/- 0.8 ppm and 25 +/- 9 mumols/l respectively (not significant). This study failed to demonstrate an effect of more efficient carbohydrate absorption with increased meal frequency. PMID- 1879387 TI - High blood pressure and marital discord: not being nasty matters more than being nice. AB - Theories linking anger and blood pressure (BP) reactivity to cardiovascular disease must be able to identify naturally occurring stressors that arouse emotion with sufficient frequency to cause chronic physiologic stress. We examine the impact of normal family arguments on 43 patients (24 women, 19 men) with essential hypertension. Patients and their partners discussed a threatening disagreement for 10 min while BP and conversation were recorded. Discussing problems increased BP, but the causal pathways differed by sex. In women, hostile interaction and marital dissatisfaction were associated with increased BP; "supportive" or "neutral" exchanges were unrelated to BP. In men, BP fluctuations were related only to the patient's speech rate. These findings are consistent with other research on sex differences in communication and social problem solving styles and implicate different mechanisms (frequent anger, active coping) through which marital discord could increase risk. Implications for intervention are considered. PMID- 1879388 TI - Mediating mechanisms in a school-based drug prevention program: first-year effects of the Midwestern Prevention Project. AB - Describes (a) the effects of a social-influences-based drug prevention program (the Midwestern Prevention Project) on the mediating variables it was designed to change and (b) the process by which the effects on mediating variables changed use of drugs (tobacco, alcohol, and marijuana). Students in 42 middle schools and junior high schools in Kansas City, Missouri, and Kansas City, Kansas, were measured in the fall of 1984 (N = 5,065) and again 1 year later (N = 5,008) after 24 of the schools had been through the program. Compared to students in control schools, students in program schools became less likely to express belief in the positive consequences of drug use, less likely to indicate that they would use such drugs in the future, more likely to report that their friends were less tolerant of drug use, and more likely to believe that they were better able to communicate with their friends about drug or school problems. Change in perceptions of friends' tolerance of drug use was the most substantial mediator of program effects on drug use. There was evidence that intentions to use and beliefs about the positive consequences of use may also mediate program effects on drug use. PMID- 1879389 TI - Effects of reviewing risk-relevant behavior on perceived vulnerability among women marines. AB - People generally underestimate their own vulnerability to negative events such as illness or accidents. It has been suggested that this illusion of "unique invulnerability" is due to selective focus on one's own risk-reducing behaviors, to the exclusion of others' risk-reducing behaviors and one's own risk-increasing behaviors. The current study examined the effects of reviewing sexual and contraceptive behavior on perceived vulnerability to unplanned pregnancy. Our results indicated that review of pregnancy-related behaviors decreased perceived vulnerability among two groups of subjects: those who considered unplanned pregnancy to be most undesirable and those who had the most confidence in the efficacy of their contraceptive behavior. The data also support the hypothesis that selective focus is a source of the illusion of invulnerability. PMID- 1879390 TI - Daily moods and symptoms: effects of awareness of study focus, gender, menstrual cycle phase, and day of the week. AB - Evaluated changes in daily ratings of moods and symptoms in 30 normally cycling women and 23 men. Women were randomly assigned to two groups for manipulating awareness of the study focus (aware vs. unaware). Principal-components analysis revealed six factors (Dysphoric Moods, Well-being, Physical Symptoms, Personal Space, Food Cravings, Depression) that accounted for 70% of the variance in daily ratings. Repeated-measures analyses revealed cyclic variation on each factor and no significant differences between aware and unaware women during premenstrual or menstrual phases on any measure. Unaware women reported less well-being than men during the premenstrual phase but did not differ on any other measure. Aware women did not differ from men in premenstrual or menstrual ratings on any measure. The way these findings relate to retrospective symptom reports, menstrual attitudes, and changes in moods and symptoms across the week was examined. PMID- 1879392 TI - Assessing daily management of childhood diabetes using 24-hour recall interviews: reliability and stability. AB - Conducted 24-hr recall interviews concerning daily diabetes management with seventy-eight 6- to 19-year-old patients and their parents. Patients and parents were interviewed independently nine times over 3 months. Data obtained were used to construct 13 adherence measures. All measures yielded statistically significant estimates of parent-child concordance. Parent-child agreement was higher for weekday versus weekend behaviors and when based on nine versus three interviews. For the sample as a whole, parent-child concordance remained stable over the course of the study. Compared to the older patients, the 6- to 9-year olds exhibited poorer parent-child agreement on measures involving time (e.g., injection and exercise-duration measures). This deficit disappeared, however, as the children became more practiced with the interview procedure. The dietary and glucose-testing measures exhibited moderate stability over the 3-month study. Lower stability estimates were obtained for the exercise and injection measures. PMID- 1879391 TI - Changes in condom use among homosexual men in San Francisco. AB - Employed data from two longitudinal surveys of gay men in San Francisco (a) to examine for cohort (Study 1) and attrition (Studies 1 and 2) bias effects on reported changes in condom use by gay men and (b) to investigate predictors of condom use (Study 2). Substantial increases in condom use were observed, and these changes were unrelated to attrition and cohort bias. In terms of predictors of condom use, men who always used condoms had higher levels of social support from informal sources of help, had more positive expectations that condoms would have positive interpersonal and personal consequences, and were more likely to be HIV positive than men who used condoms occasionally or never. The results are discussed in terms of their implications for HIV-prevention research. PMID- 1879393 TI - Fluid noncompliance and symptomatology in end-stage renal disease: cognitive and emotional variables. AB - Fluid noncompliance in patients with end-stage renal disease (ESRD) is a widespread problem with severe consequences for health. In addition, ESRD patients report considerable stress in relation to their illness and dialysis treatment. The present study examined the role of cognitive and emotional variables in fluid noncompliance, symptomatology, and stress. Fifty hemodialysis patients were assessed (a) on the cognitive variables of locus of control, self evaluations of their past compliance, and self-efficacy to resist fluid intake and (b) on the emotional variables of depression, anger, and anxiety. Results showed that cognitive variables accounted for fluid noncompliance and predicted future adherence. Patients high in negative emotions complied equally as well as patients low in negative emotions but were found to report substantially more symptomatology and distress associated with their treatment. The implications of these findings for treatment of ESRD patients and future research are discussed. PMID- 1879394 TI - Weight gain and withdrawal symptoms after smoking cessation: a preventive intervention using d-fenfluramine. AB - Directly measured food intake in 31 overweight female smokers to test whether (a) calorie and carbohydrate intakes increase after smoking cessation and (b) double blind d-fenfluramine (30 mg), a serotonin-releasing drug, suppresses weight gain, overeating, and dysphoric mood associated with stopping smoking. Placebo-treated patients grew dysphoric after smoking withdrawal and ate 300 kcal/day more from 2 to 28 days after, showing a 3.5-lb weight gain. Fat and protein intakes did not change, but carbohydrate intake increased (30% to 40%). D-fenfluramine prevented postcessation dysphoria. Although drug-treated patients ate more carbohydrate snacks just after quitting, they returned to baseline by 4 weeks, showing a 1.8 lb weight loss. Agents that enhance brain serotonin-mediated neurotransmission may help prevent weight gain, overeating, and dysphoric mood after smoking withdrawal. PMID- 1879396 TI - New aspects of adrenal cortical disease. PMID- 1879395 TI - Is response adaptation a threat to the high-low reactor distinction among female college students? AB - Examined cardiovascular-response adaptation patterns in high- versus low cardioreactive women. Responses to a mental-arithmetic-plus-noise task were compared within trials (3 min each), across trials (three per session), and across two sessions separated by a 4-week interval. Forty-four normotensive women (mean age = 22.5 years) completed the study. Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were monitored. Analyses of variance were employed to analyze the repeated-measures design and indicated consistent decreases in HR, SBP, and DBP response magnitudes across visits, trials, and minutes. Decreases in HR were greatest from Minute 1 to Minute 2 within each trial and, similarly, from Trial 1 to Trial 2 within each visit. BP responses showed a delayed onset of within-trial adaptation. Reactivity groups were formed for (a) SBP reactivity for HR and DBP analyses and (b) HR reactivity for SBP analyses. Although high reactors (top tercile) showed greater adaptation to task repetition in all responses compared to low reactors (lowest tercile), they also consistently displayed greater responses. Even during the final task, SBP and HR responses discriminated between high and low reactors. PMID- 1879397 TI - Diagnosis of hyperaldosteronism. AB - Hyperaldosteronism is associated with hypertension, potassium depletion, and suppressed plasma renin activity. It may involve one or both adrenal glands. This article reviews the different types of hyperaldosteronism and the diagnosis and management of each. PMID- 1879398 TI - 17 alpha-hydroxylation deficiency. AB - Cases of sexual immaturity and male pseudohermaphroditism due to disorders such as androgen resistance, 5 alpha-reductase deficiency, cholesterol desmolase deficiency, 3 beta-hydroxysteroid dehydrogenase deficiency, and testicular and ovary dysgenesis can easily be distinguished from 17 alpha-OHD. None of these disturbances result in hypertension. In the only other form of juvenile hypertension due to congenital adrenal hyperplasia, 11 beta-OHD, androgen excess leads to female pseudohermaphroditism and precocious puberty in the male patient. Patients with dexamethasone-suppressible hyperaldosteronism present with no sexual abnormalities. A diagnosis of 17 alpha-OHD can be readily assumed in the female patient with primary amenorrhea, hypertension, and hypokalemia. The absence of aldosterone, a measurement that is readily available, establishes this diagnosis even without the measurement of DOC. PMID- 1879399 TI - Two uncommon causes of mineralocorticoid excess. Syndrome of apparent mineralocorticoid excess and glucocorticoid-remediable aldosteronism. AB - Glucocorticoid-remediable aldosteronism is an inherited form of mineralocorticoid excess associated with moderate overproduction of aldosterone, in which biochemical and clinical remission is dramatically induced by small amounts of glucocorticoids. The disorder is associated with characteristic overproduction of 18-hydroxycortisol and 18-oxocortisol, which must now be regarded as an essential diagnostic feature and also as an aid in the detection of the disorder in the face of partial clinical expression. PMID- 1879400 TI - Congenital adrenal hyperplasia caused by 21-hydroxylase deficiency. Its molecular basis and its remaining therapeutic problems. AB - This article discusses congenital adrenal hyperplasia (CAH) caused by a deficiency of 21-hydroxylase, which represents 90% of all cases of CAH. As in other genetic disorders of metabolism, the symptoms of CAH are related to both the decrease of the final products of metabolism and the accumulation of precursors that are not normally secreted or that are secreted in only very small amounts. The biochemistry, pathophysiology, treatment, genetics, and long-term follow-up (including fertility and sexual orientation) of both the simple virilizing form and the salt-losing form of 21-hydroxylase deficiency are presented, as well as the possibility of prenatal treatment. PMID- 1879401 TI - Adrenoleukodystrophy. AB - X-linked adrenoleukodystrophy (ALD) is a disorder of very long chain fatty acid (VLCFA) metabolism that can be diagnosed by demonstrating increased levels of VLCFA in plasma and, prenatally, by similar assays in cultured amniocytes or chorionic vilus samples. ALD causes Addison disease frequently in men and occasionally in women. Prompt diagnosis is important for genetic counseling and for the institution of therapies aimed to prevent or ameliorate the progressive neurologic disability that often is associated with this illness. PMID- 1879402 TI - Dysregulation of aldosterone secretion and its relationship to the pathogenesis of essential hypertension. AB - The level of sodium intake has a reciprocal influence on the vascular and adrenal responses to angiotensin II, with sodium restriction enhancing the adrenal responses and reducing vascular, and particularly renal vascular, responses. In two subgroups of the essential hypertensive population, this relationship is abnormal. Both subgroups have sodium-sensitive hypertension. One is a subset of the low renin essential hypertensive subgroup and its abnormality is an enhanced aldosterone response to angiotensin II with sodium loading, ie, a failure to down regulate the aldosterone response. The other subgroup, termed nonmodulators, is a subset of the normal-high renin essential hypertensive subgroup. In these patients, sodium intake modifies either adrenal or vascular responses, including renal vascular responses, to angiotensin II--resulting in a reduced aldosterone response to angiotensin II with sodium restriction. Of clinical importance, the nonmodulator's abnormality is corrected by the administration of converting enzyme inhibitors--this class of drugs therefore being a specific form of therapy in these patients. PMID- 1879403 TI - Sex and strain differences in the hepatocyte primary culture/DNA repair test. AB - The hepatocyte primary culture (HPC)/DNA repair test was developed using hepatocytes isolated from male F-344 rats. A number of genetic polymorphisms have been shown to occur in inbred strains of rats, which may lead to variation in biotransformation of xenobiotics resulting in differences in susceptibility to genotoxins. The effect of the strain utilized as a source of hepatocytes was investigated with female Lewis, F-344, and DA rats. Variation was observed when hepatocytes from the three strains were exposed to aflatoxin B1 (AFB1). Hepatocytes from female Lewis rats were more sensitive to AFB1 genotoxicity than cells from F-344 or DA rats. DNA repair was induced by a concentration as low as 10(-8) M AFB1 in the Lewis strain while 10(-4) M was needed for hepatocytes from female F-344 or DA rats. Sex-related differences were also observed with AFB1; DNA repair was induced at 10(-8) M in hepatocytes from male F-344 rats. No clearcut strain differences were seen when cells were exposed to diethylnitrosamine (DEN) or 2-acetylaminofluorene, although 10(-2) M DEN was only cytotoxic to hepatocytes from DA rats. These results demonstrate that both the strain and the sex of the animal used as a source of hepatocytes can affect the HPC/DNA repair test. PMID- 1879404 TI - Comparison of hprt variant frequencies and chromosome aberration frequencies in lymphocytes from radiotherapy and chemotherapy patients: a prospective study. AB - The autoradiographic 6-thioguanine-resistant mutant lymphocyte assay and a chromosome aberration assay were used to determine the time-course of appearance and persistence of elevated frequencies of hprt variants and dicentric chromosomes in patients receiving x-irradiation therapy. Twelve cancer patients, treated with 180-200 cGy/day, 5 days/wk, for 3-7 wk, were studied before treatment, at various weekly intervals during treatment, and after treatment. The hprt mutation assays were done with frozen/thawed lymphocytes isolated from aliquots of the same blood samples used for the chromosome aberration assays. The hprt variant frequencies (Vfs) of only 4 of the 7 patients assayed at 2 wk of treatment were elevated over pre-treatment Vfs, but during the 3rd and 4th weeks of treatment there were significant (P less than 0.01) 5- to 15-fold increases in all Vfs. By 6-32 wk after treatment Vfs had fallen to levels only slightly higher than the mean pre-treatment Vf. The frequencies of cells with dicentric chromosomes were significantly increased (P less than 0.01) after 1 wk of radiotherapy, continued to increase during therapy, and remained elevated after treatment. Five multiple sclerosis patients were also studied before and at 2 and 4 wk intervals after treatment with monthly i.v. doses of 750 mg/m2 of cyclophosphamide (CP). There were no significant elevations in chromosome aberrations at these post-treatment sample times. Previous assays for hprt mutants, done with aloquots of the same blood samples (Ammenheuser et al.: Mutat Res 204:509-520, 1988), had shown 8- to 20-fold increases in Vfs 2 wk after the 1st CP treatment. Our results demonstrate the complementary nature of these two human monitoring assays and emphasize the importance of careful selection of optimal sampling times. PMID- 1879405 TI - Frequency of sister chromatid exchange in peripheral lymphocytes of male pesticide applicators. AB - In the present study 61 male pesticide applicators who worked in cotton fields and regularly sprayed pesticides such as DDT, BHC, endosulfan, malathion, methyl parathion, phosphamidon, dimethoate, monocrotophos, quinalphos fenvelrate, and cypermethrin were analyzed for sister chromatid exchanges, mitotic index, and cell cycle kinetics in peripheral lymphocytes. Subjects who handled pesticides were non-smokers and teetotalers and the data were compared with the matched control group. Statistical analysis revealed that the frequency of sister chromatid exchanges was significantly higher among the pesticide applicators at all the durations of exposure when compared to controls. Subjects exposed to pesticides also showed cell cycle delay and decrease in mitotic index when compared to the control group. PMID- 1879406 TI - Flow cytometric evaluation of cell-cycle progression in ethyl methanesulfonate and methyl methanesulfonate-exposed P3 cells: relationship to the induction of sister-chromatid exchanges and cellular toxicity. AB - In order to determine the relationships among the reduction in relative cloning efficiency (RCE), sister-chromatid exchange (SCE) formation, and interference with progression through the cell-cycle, human teratocarcinoma-derived (P3) cells were exposed to either ethyl methanesulfonate or to methyl methanesulfonate. The relationship between SCE and toxicity was quantified, the progression through the cell-cycle was evaluated with flow cytometric methods, and the effects of these chemicals on cell growth and average generation time (AGT) were determined. A strong correlation existed between RCE and SCE (r = -0.978, p less than .001) which was accompanied by an inhibition of growth as evidenced by a significant (p less than .0001) negative linear effect of concentration on the relative cell count from 24 to 72 hours after exposure and by a concentration-dependent increase (p less than .0001) in the AGT. Delays in the transit through S-phase were evident 4 hours after exposure to toxic concentrations of either carcinogen and by 8 to 12 hours post-exposure at the lower concentrations. Increases in the percentage of nuclei in G2 + M, indicative of G2 arrest, occurred from 12 to 24 hours after exposure. One interpretation of these results is that those effects of EMS and MMS exposure which result in S-phase delay and G2 arrest may be those elements common to the induction of SCE and cellular toxicity. PMID- 1879407 TI - Cytogenetic damage induced in vivo to mice by single exposure to cesium chloride. AB - Female laboratory bred albino mice (2n = 40) were orally administered cesium chloride (CsCl) in aqueous solution as a single dose and the damage induced at the chromosomal level was observed in bone marrow cells after 6, 12, 18, and 24 hours of exposure. The concentrations of the chemical given were calculated as fractions of the LD50, namely 1/5, 1/10, and 1/20. The cytogenetic endpoints screened for were chromosomal aberrations (CA) and divisional frequency or mitotic index (MI). The frequency of chromosomal aberrations induced was directly proportional to the concentration of the chemical administered. The highest dose was the most toxic and was considered to be the maximum tolerance level. Effects on divisional frequency were variable, the highest concentration being significantly mitostatic, the middle one ineffective, and the lowest slightly mitogenic. In general, the observations indicate that CsCl is clastogenic when administered orally to mice in vivo and the effects are dose-dependent. PMID- 1879409 TI - The Laryngeal Mask--a non-invasive airway. PMID- 1879408 TI - Effect of pentachlorophenol on the activation of 2,6-dinitrotoluene to genotoxic urinary metabolites in CD-1 mice: a comparison of GI enzyme activities and urine mutagenicity. AB - 2,6-Dinitrotoluene (2,6-DNT) and pentachlorophenol (PCP) are used for industrial purposes and are found in the environment as hazardous contaminants. Because concurrent exposure to both compounds can occur, it is of interest to determine if organochlorine compounds potentiate the effect of nitroaromatic chemicals. CD 1 mice were treated with PCP (42.8 mg/kg) for 4 weeks. On weeks 1, 2, and 4 after the initial PCP dose, mice were treated p.o. with 2,6-DNT (75 mg/kg) and 24 hr urines were collected. After concentration, the urines were tested for their mutagenic activity in Salmonella typhimurium strain TA98 without metabolic activation in a microsuspension bioassay. A significant increase (P less than .05) in mutagenicity was observed in urines from mice treated with 2,6-DNT alone and in combination with PCP. By week 4, mice that received both 2,6-DNT and PCP excreted urine that was more mutagenic than that from animals which received only 2,6-DNT. At weeks 2 and 4, mice were sacrificed and intestinal enzyme activities (nitroreductase, azo reductase, beta-glucuronidase, dechlorinase, and dehydrochlorinase) were quantitated. The enhanced genotoxicity observed in urines from 2,6-DNT/PCP-treated mice coincided with a decrease in nitroreductase and an increase in beta-glucuronidase activities in the small intestine. PMID- 1879410 TI - The Laryngeal Mask--an overview. AB - New equipment, like a new drug, encourages a high level of reporting of adverse events, which can lead to the very rapid identification of even relatively rare complications. When considering the merit of one drug versus another, unless either have major defects, then the result will depend upon the overall picture, i.e. the sum of the morbidities associated with one versus the sum associated with another. Other factors such as availability, purity, and cost will also be taken into consideration. The LM is very recent in the time scale of the history of 'anaesthesia', but it would appear to have survived the 'major defect' stage, and to have entered the trial by morbidity stage. A definite answer on the question of regurgitation and aspiration is not yet available. Present evidence indicates, however, that where there is no contra-indication to it and provided that meticulous attention is paid to mode of use, the LM can be helpful in a wide variety of situations. It is an extremely innovative, and occasionally life saving piece of equipment, and the relatively small effort necessary to acquire skill in its use worth making. A future review will be able to incorporate the results of on-going and planned studies, and may more accurately define its place in anaesthesia and resuscitation. PMID- 1879411 TI - Radiological study of the Laryngeal Mask. AB - Lateral soft-tissue radiography was used to determine the location of the Laryngeal Mask (LM) in relation to the larynx and surrounding structures in 24 elderly male patients undergoing general anaesthesia. In a majority of cases (16 of 24) the epiglottis was within the cuff of the mask but without causing discernable airway obstruction in any case. One case of backfolding of the cuff occurred, and there was one case of gross misplacement (also clinically undetected). Supplementary information was obtained in 13 patients by the use of fibre-optic endoscopy, via the lumen of the LM, confirming the inclusion of the epiglottis within the mask and demonstrating a characteristic distortion by the LM of the normal laryngeal anatomy. It is concluded that inclusion of the epiglottis within the LM is commonplace, and misplacements may occur without clinical evidence of a compromised airway. PMID- 1879412 TI - Endotracheal intubation through the Laryngeal Mask--helpful when laryngoscopy is difficult or dangerous. AB - The correctly placed Laryngeal Mask will act as a guide to endotracheal intubation in over 90% of adult patients. Although the size of tube is limited to a 6-mm-internal-diameter cuffed oral or nasal pattern tube the technique is easy to learn and can provide a rapid solution when endotracheal intubation is necessary but conventional laryngoscopy is unexpectedly difficult or dental restorations are at risk. Application of cricoid pressure reduces the success rate of the technique; therefore, if this manoeuvre is indicated to reduce the risks of regurgitation, anaesthetists are advised to arrange for its momentary relaxation during the final stages of placement of the Laryngeal Mask and of the endotracheal tube. PMID- 1879413 TI - Difficult intubation and the Laryngeal Mask. AB - The Laryngeal Mask (LM) can be used to intubate patients in whom conventional direct laryngoscopy is difficult. Tracheal intubation can be achieved using the LM alone but the use of a fibre-optic laryngoscope increases the chances of success. PMID- 1879414 TI - The development of the Laryngeal Mask--a brief history of the invention, early clinical studies and experimental work from which the Laryngeal Mask evolved. AB - The history of the invention and development of the Laryngeal Mask in the East End of London during the years 1981-88 is briefly described. The concept evolved from home-made prototypes built from the Goldman Dental Mask through a complex series of one-off latex models culminating in a primitive factory-made silicone cuff in 1986. This work defined the design parameters necessary to reconcile the needs for safety, reliability and ease of insertion while at the same time exploring the limits to possible use. In early 1988 the final version was tested by the inventor who had by this time used the device in more than 7500 patients undergoing routine surgery. From this experience a number of important lessons were learned relating to safe and effective use, which are summarized in the inventor's Instruction Manual. The importance of referring to this volume before use is stressed. PMID- 1879415 TI - The Laryngeal Mask in dental anaesthesia. PMID- 1879416 TI - Cloning and sequence analysis of cDNA encoding two crustacean hyperglycemic hormones from the lobster Homarus americanus. AB - Using the polymerase chain reaction with degenerated oligonucleotides, we have isolated cDNA clones that encode two structurally different (92% identity) crustacean hyperglycemic hormones (CHH) from the lobster Homarus americanus. The deduced amino acid sequences fully agree with previously published data on partial amino acid sequences, amino acid compositions and molecular masses of hyperglycemic peptides in the lobster. A comparative analysis between the deduced primary structure of two lobster CHH and the crab CHH sequence reveals a phylogenetic relationship and allows the prediction of biologically important regions within the structures of these novel neuropeptides. PMID- 1879417 TI - The primary structure of hevamine, an enzyme with lysozyme/chitinase activity from Hevea brasiliensis latex. AB - The primary structure of hevamine, an enzyme with lysozyme/chitinase activity from Hevea brasiliensis latex, has been determined predominantly with conventional non-automatic methods. The positions of three disulfide bridges have been determined. The sequence has about 60% identity with that of a chitinase from cucumber and 95% with the N-terminal sequence of the lysozyme/chitinase of Parthenocissus quinquefolia. The half-cystine residues in hevein and cucumber chitinase are located at identical positions. Hevamine is a basic protein from the lutoids (vacuoles) of rubber latex and may have a role in plugging the latex vessels and cessation of latex flow. The differences in cellular location, charge properties and sequence between hevamine and cucumber chitinase are similar to those between class I and class II chitinases from tobacco and other plant species. PMID- 1879418 TI - Purification and characterization of a chicken egg white cystatin variant expressed in an Escherichia coli pIN-III-ompA system. AB - A synthetic gene coding for a chicken egg white cystatin variant was cloned and expressed using the pIN-III-ompA Escherichia coli expression system. After osmotic shock of the E. coli cells, the cysteine proteinase inhibitor was isolated from periplasm and purified by S-carboxymethylpapain affinity chromatography. The resulting inhibitory material was characterized by SDS/PAGE, reversed-phase HPLC, peptide mapping and amino acid sequencing. The recombinant variant chicken AEF-[S1----M, M29----I, M89----L]cystatin shows strong inhibitory activity and displays Ki values in the complex with papain, actinidin and cathepsin B similar to those found for natural chicken cystatin. The purified variant showed a native-chicken-cystatin-like conformational state, as determined by NMR spectroscopy, if the NMR data of 15N-labelled recombinant inhibitor were compared with those of the natural inhibitor. PMID- 1879419 TI - Characterization of wild-type and mutant M13 gene V proteins by means of 1H-NMR. AB - Recording of good quality NMR spectra of the single-stranded DNA binding protein gene V of the bacteriophage M13 is hindered by a specific protein aggregation effect. Conditions are described for which NMR spectra of the protein can best be recorded. The aromatic part of the spectrum has been reinvestigated by means of two-dimensional total correlation spectroscopy. Sequence-specific assignments were obtained for all of the aromatic amino acid residues with the help of a series of single-site mutant proteins. The solution properties of the mutants of the aromatic amino acid residues have been fully investigated. It has been shown that, for these proteins, either none or only local changes occur compared to the wild-type molecule. Spin-labeled oligonucleotide-binding studies of wild-type and mutant gene V proteins indicate that tyrosine 26 and phenylalanine 73 are the only aromatic residues involved in binding to short stretches of single-stranded DNA. The degree of aggregation of wild-type gene V protein is dependent on both the total protein and salt concentration. The data obtained suggest the occurrence of specific protein-protein interactions between dimeric gene V protein molecules in which the tyrosine residue at position 41 is involved. This hypothesis is further strengthened by the observation that the solubility of tyrosine 41 mutants of gene V protein is significantly higher than that of the wild-type protein. The discovery of the so-called 'solubility' mutants of M13 gene V protein has finally made it possible to study the solution structure of gene V protein and its interaction with single-stranded DNA by means of two dimensional NMR. PMID- 1879420 TI - The endo-1,4-beta-glucanase I from Trichoderma reesei. Action on beta-1,4 oligomers and polymers derived from D-glucose and D-xylose. AB - The reaction mechanism of the non-specific endo-1,4-beta-glucanase from Trichoderma reesei QM 9414 (endoglucanase I) was investigated using both reducing end3H-labelled and universally 14C-labelled cellooligosaccharides, as well as reducing-end3H-labelled xylooligosaccharides. The bond cleavage frequencies of cellooligosaccharides proved to be dependent upon the substrate concentration, especially in the case of cellotriose. In addition to simple hydrolytic cleavage, the enzyme catalyzes reactions along alternative pathways, including transglycosylations leading to products larger than the substrate. Some of these pathways were shown to be reversible. During cellotriose or cellopentaose degradation, substrate resynthesis was demonstrated by incorporation of added radioactive D-glucose or cellobiose. The endoglucanase I is active on xylan and xylooligosaccharides, but less than on soluble cellulose derivatives (e.g. hydroxyethylcellulose) and cellooligosaccharides. The fact that for these different types of substrates the same active site is operative is proven by the ability of the enzyme to utilize cellooligosaccharides and xylooligosaccharides as both glycosyl donors and acceptors. The mixed substrate reactions lead to products composed of D-glucosyl and D-xylosyl residues. The kinetic parameters for cellooligosaccharide degradation can be used for the description of an extended substrate binding site. Of the four putative glycosyl subsites, -II and +II show the highest affinities, 16.7 kJ.mol-1 and 7.1 kJ.mol-1, respectively. PMID- 1879421 TI - Amino acid alterations essential for increasing the catalytic activity of the nylon-oligomer-degradation enzyme of Flavobacterium sp. AB - The structural genes of two homologous enzymes, 6-aminohexanoate-dimer hydrolase (EII; nylB) and its evolutionally related protein EII' (nylB') of Flavobacterium sp. KI72 have an open reading frame encoding a peptide of 392 amino acids, of which 47 are different, and conserved restriction sites. The specific activity of EII towards 6-aminohexanoate dimer is about 1000-fold that of EII'. Construction of various hybrid genes obtained by exchanging fragments flanked by conserved restriction sites of the two genes demonstrated that two amino acid replacements in the EII' enzyme, i.e. Gly181----Asp (EII type) and His266----Asn (EII type), enhanced the activity toward 6-aminohexanoate dimer 1000-fold. PMID- 1879423 TI - Catabolism of platelet-activating factor and its acyl analog. Differentiation of the activities of lysophospholipase and platelet-activating-factor acetylhydrolase. AB - Recent investigations have shown the presence of 1-acyl-2-acetyl-sn-glycero-3 phosphocholine, i.e. the acyl analog of platelet-activating factor (PAF), in unstimulated tissues as well as its formation along with platelet-activating factor upon stimulation of a variety of cells. We demonstrate here that this acyl analog of PAF can be catabolized by purified lysophospholipases I and II from bovine liver with near stoichiometric formation of 2-acetyl-sn-glycero-3 phosphocholine. Lysophospholipase II also deacetylated PAF to lysoPAF and evidence is presented to show that this is an intrinsic activity of this enzyme. This suggested that some lysophospholipases may contribute to intracellular inactivation of PAF by deacetylation. Anion-exchange chromatography of rat liver cytosol confirmed this possibility. However, similar experiments with rat kidney cytosol and rat and human platelet cytosol clearly separated lysophospholipase activities without PAF acetylhydrolase activity from specific PAF acetylhydrolases not having lysophospholipase activity. Thus, lysophospholipases are clearly involved in the metabolism of the acyl analog of PAF and in some tissues, such as liver, may even contribute to abolishing the biological activity of PAF through deacetylation. PMID- 1879422 TI - Evidence for a peroxisomal fatty acid beta-oxidation involving D-3-hydroxyacyl CoAs. Characterization of two forms of hydro-lyase that convert D-(-)-3 hydroxyacyl-CoA into 2-trans-enoyl-CoA. AB - A novel D-(-)-3-hydroxyacyl-CoA hydro-lyase, forming 2-trans-enoyl-CoA and formerly designated as epimerase (EC 5.1.2.3), was extracted from fat-degrading cotyledons of cucumber seedlings. The enzyme, called D-3-hydroxyacyl-CoA hydro lyase or D-specific 2-trans-enoyl-CoA hydratase, is shown to be required for the degradation of unsaturated fatty acids that contain double bonds extending from even-numbered C atoms. The D-3-hydroxyacyl-CoA hydro-lyase was exclusively localized within peroxisomes. A 10,000-fold purification by chromatography on a hydrophobic matrix, a cation exchanger, on hydroxyapatite and Mono S led to two proteins of apparent homogeneity, both exhibiting Mr of 65,000. The D-3 hydroxyacyl-CoA hydro-lyases are homodimers with slightly differing isoelectric points around pH = 9.0. They catalyze the conversion of 2-trans-enoyl-CoA into D 3-hydroxyacyl-CoA. The reverse reaction was observed but no reaction with 2-cis enoyl-CoAs or L-3-hydroxyacyl-CoAs. 2-trans-Decenoyl-CoA was converted 10-times faster than 2-trans-butenoyl-CoA. The conversion of 4-cis-decenoyl-CoA into octenoyl-CoA was demonstrated in vitro with purified proteins with an assay mixture containing acyl-CoA oxidase, multifunctional protein, thiolase and the D 3-hydroxyacyl-CoA hydro-lyase. Comparisons of enzyme activities present in the cotyledons or isolated peroxisomes clearly show that the pathway via dienoyl-CoA reductase is much less effective than the sequence involving D-3-hydroxyacyl-CoA hydro-lyase. PMID- 1879424 TI - Molecular cloning and analysis of two tandemly linked genes for pyruvate kinase of Trypanosoma brucei. AB - In Trypanosoma brucei (stock 427) genes encoding the glycolytic enzyme pyruvate kinase are present on two homologous chromosomes. We have cloned and characterized one of the alleles. Two large, tandemly arranged open reading frames were found, each coding for a pyruvate kinase polypeptide of 498 amino acids. The gene sequences differ at 15 positions, resulting in five amino acid substitutions. The calculated molecular masses of the polypeptides are 54,378 Da and 54,363 Da. These values are somewhat smaller than those reported for the subunit molecular mass of the purified protein, which is 57-59 kDa. However, in vitro translation of the DNA region corresponding to the open reading frame, and translation of the RNA in a wheat-germ lysate, yielded a product that comigrated exactly with the native polypeptide in SDS/PAGE. The overall identity between the sequences of the trypanosomal enzyme and the enzymes from other sources is 41 51%. The conserved residues are not equally distributed over the polypeptide. The primary structure of domains A and, to a lesser extent, B, which constitute the active site, are rather well conserved. In contrast, the sequence of domain C, which supposedly is involved in the regulation of the enzyme activity, is much more variable. The cytosolically located pyruvate kinase of T. brucei lacks the specific features found in the majority of the glycolytic enzymes of this organism that are sequestered in a microbody-like organelle, the glycosome. It has neither a relatively high subunit molecular mass, due to unique insertions or terminal extensions, nor a high excess of positively charged amino acids. The polypeptide is shorter than that of most other pyruvate kinases and the calculated net charge is only +3. PMID- 1879425 TI - Inhibition of the Na+/I- symporter by harmaline and 3-amino-1-methyl-5H pyrido(4,3-b)indole acetate in thyroid cells and membrane vesicles. AB - Novel inhibitors of the Na+/I- symporter were identified using rat-thyroid derived FRTL-5 cells and sealed vesicles from calf thyroid as model systems. Na(+)-dependent 125I- uptake was inhibited by the hallucinogenic drug harmaline and by a chemically related convulsive agent, 3-amino-1-methyl- 5H-pyrido(4,3 b)indole acetate (TRP-P-2). TRP-P-2 (Ki = 0.25 mM) was tenfold more effective as an inhibitor than harmaline (Ki = 4.0 mM). Inhibition by TRP-P-2 was competitive with respect to Na+ and was fully reversible. Although TRP-P-2 is a relatively low-affinity inhibitor, its affinity for the Na+ site of the Na+/I- symporter is over 100 times higher than that of Na+ (Km = 50 mM). 45Ca(2+)-efflux rates in calf thyroid membrane vesicles were not affected by TRP-P-2, indicating that membrane integrity is not disrupted by the drug. These findings show that TRP-P-2 may be a potentially useful tool for the identification and characterization of the Na+/I- symporter. PMID- 1879426 TI - Characterization of a quinole-oxidase activity in crude extracts of Thermoplasma acidophilum and isolation of an 18-kDa cytochrome. AB - A quinol-oxidase activity was detected in crude extracts of the thermoacidophilic archaebacterium Thermoplasma acidophilum. The activity was optimal at pH 5.4 and 50 degrees C. The Km for ubiquinol-10 was 18 microM. The enzyme was inhibited by 2n-heptyl-4-hydroxyquinoline N-oxide with a Ki of 150 nM. Ubiquinols with different side-chain lengths were oxidized at similar rates, whereas menaquinols were converted at 6-12-fold higher rates compared to ubiquinols. Membranes from T. acidophilum contain cytochromes of b, d and a1 types, as shown by optical spectroscopy. CO difference spectroscopy suggests the existence of a cytochrome o. A b-type cytochrome with an apparent molecular mass of 18 kDa was purified in the presence of high detergent concentrations. It readily forms dimers on SDS/PAGE. This cytochrome also contains Cu, as shown by atomic-absorption spectroscopy. Redox titration suggests that the 18-kDa cytochrome may contain 2 heme groups; b558 with a midpoint potential of 75 mV and b562/553 with a midpoint potential of -150 mV. PMID- 1879427 TI - Quantitative assessment of regulation in metabolic systems. AB - We show how metabolic regulation as commonly understood in biochemistry can be described in terms of metabolic control analysis. The steady-state values of the variables of metabolic systems (fluxes and concentrations) are determined by a set of parameters. Some of these parameters are concentrations that are set by the environment of the system; they can act as external regulators by communicating changes in the environment to the metabolic system. How effectively a system is regulated depends both on the degree to which the activity of the regulatory enzyme with which a regulator interacts directly can be altered by the regulator (its regulability) and on the ability of the regulatory enzyme to transmit the changes to the rest of the system (its regulatory capacity). The regulatory response of a system also depends on its internal organisation around key variable metabolites that act as internal regulators. The regulatory performance of the system can be judged in terms of how sensitivity the fluxes respond to the external stimulus and to what degree homeostasis in the concentrations of the internal regulators is maintained. We show how, on the level of both external and internal regulation, regulability can be quantified in terms of an elasticity coefficient and regulatory capacity in terms of a control coefficient. Metabolic regulation can therefore be described in terms of metabolic control analysis. The combined response relationship of control analysis relates regulability and regulatory capacity and allows quantification of the regulatory importance of the various interactions of regulators with enzymes in the system. On this basis we propose a quantitative terminology and analysis of metabolic regulation that shows what we should measure experimentally and how we should interpret the results. Analysis and numerical simulation of a simple model system serves to demonstrate our treatment. PMID- 1879428 TI - 2,4-diamino-7-hydroxy-pteridines, a new class of catabolites of methotrexate. AB - Methotrexate remains a commonly used drug in the chemotherapy of various malignancies. The known catabolites are 7-hydroxy-methotrexate, formed in the liver, and diamino-methyl-pteroic acid formed in the gut. We report for the first time evidence that 2,4-diamino-7-hydroxy-pteridine derivatives are present in the biological fluids of patients on high-dose methotrexate protocols. So far, two major derivatives have been identified as 2,4-diamino-6-hydroxymethyl-7-hydroxy pteridine and 2,4-diamino-6-methyl-7-hydroxy-pteridine. In regard to the actual knowledge of the catabolism of pteridines, these compounds are presumably formed by intestinal bacteria during enterohepatic circulation of the drug. Their slow clearance from the body raises the question of possible interference of these compounds on pteridine-dependent enzymes, which might explain in part some of the toxic effects of methotrexate. PMID- 1879429 TI - Effects of ethanol and clofibrate on expression of cytochrome P-450 enzymes and epoxide hydrolase in cultures and cocultures of rat hepatocytes. AB - Cultured and cocultured rat hepatocytes were used to study the effects of ethanol and clofibrate on cytochrome P-450 (P-450) enzymes and epoxide hydrolase. We showed that in the presence of ethanol, clofibrate or both compounds, rat hepatocytes were able to express, after 3 days of pure culture, quantitatively and qualitatively reasonable levels of most cytochrome P-450 enzymes and epoxide hydrolase, compared to freshly isolated hepatocytes. However, ethanol induced the P-450IA subfamily, and clofibrate the P-450-IVA subfamily. In cocultures, after 6 days, most P-450 enzymes were still expressed while P-450IIC11 was completely lost. Ethanol and clofibrate had the same effect as in pure culture. These results show, by modifying culture medium conditions and cell-cell interactions, that it is possible to maintain reasonable xenobiotic-metabolizing-enzyme expression; however, these conditions have to be improved in order to preserve better P-450 expression. The mechanism of these effects and the inducibility of these systems remain to be elucidated by a study at molecular level. PMID- 1879430 TI - Interference with myosin subfragment-1 binding by site-directed mutagenesis of actin. AB - Three N-terminal double mutants of beta-actin expressed in the yeast Saccharomyces cerevisiae have been characterized with respect to DNase-I interaction, N-terminal post-translational modification, polymerizability and myosin subfragment-1 binding. The results strongly support earlier suggestions that the acidic residues at the N-terminus of actin are part of the myosin binding site, while they seem to be of no importance for the other aspects of actin biochemistry tested. The suitability of this expression system for production of recombinant actin in general is discussed. PMID- 1879431 TI - Purification and properties of F420- and NADP(+)-dependent alcohol dehydrogenases of Methanogenium liminatans and Methanobacterium palustre, specific for secondary alcohols. AB - The F420-dependent alcohol dehydrogenase (ADH) of Methanogenium liminatans and the NADP(+)-dependent ADH of Methanobacterium palustre were purified to homogeneity. The native F420-dependent ADH of Mg. liminatans had a molecular mass of 150 kDa and consisted of four (presumably identical) subunits with a mass of 39 kDa. The temperature optimum was 42 degrees C, the optimum pH 6.0 and NaCl or KCl were inhibitory. The NADP(+)-dependent ADH of Mb. palustre had a molecular mass of 175 kDa and consisted also of four (presumably identical) subunits with a mass of 44 kDa. The temperature optimum was 60 degrees C, the optimum pH 8.0 and optimal activity was observed in the presence of 500 mM NaCl or KCl. The ADHs of both organisms catalysed the oxidation of various secondary and cyclic alcohols to the corresponding ketones and the reverse reaction. No primary alcohols were apparently oxidized. The NADP(+)-dependent ADH of Mb. palustre contained 4-8 mol atoms zinc/mol enzyme and was inhibited by low concentrations of iodoacetate and 4-hydroxymercuribenzoate, whereas the F420-dependent ADH of Mg. liminatans presumably contained no zinc ions and was inhibited by 1,10-phenanthroline or high concentrations (e.g. 100 microM) of 4-hydroxymercuribenzoate. Polyclonal antibodies against the NADP(+)-dependent ADH of Mb. palustre precipitated only the homologous ADH. A precipitation of the NADP(+)-dependent ADH of Methanocorpusculum parvum required a 10-fold higher antibody concentration, showing at least a distant relationship of both ADHs. Antibodies against the NADP(+)-dependent ADH of Mcp. parvum, however, formed precipitates with the homologous ADH of Mcp. parvum and with the NADP(+)-dependent ADH of Mb. palustre. They also formed precipitates with the ADH of Thermoanaerobium brockii, which is not related to methane bacteria. Antibodies against the F420-dependent ADH of Mg. liminatans reacted only with the homologous enzyme and did not form precipitates with NADP(+)-dependent ADHs. No immunological relation of the NADP(+)- or F420 dependent ADHs of methanogens with ADH of yeast or horse liver was found. In accordance with the immunological data, the N-terminal amino acid sequences of the NADP(+)-dependent ADHs of Mb. palustre and Mcp. parvum had a high degree of similarity, whereas the N-terminal amino acid sequence of the ADH of Mg. liminatans revealed no similarity with the two NADP(+)-dependent enzymes. PMID- 1879432 TI - The mouse S-antigen gene. Comparison with human and Drosophila. AB - We have characterized a gene for mouse S-antigen and compared its sequence with that of corresponding human and two recently published Drosophila S-antigen genes. The mouse S-antigen gene was approximately 50 kbp in length and consisted of 16 exons and 15 introns. The length of most exons was less than 100 bp and the smallest one was only 10 bp. In contrast, the length of most introns was larger than 2 kbp and the gene consisted of 97% intron and 3% exon. Both splice sites for donor and accepter were in good agreement with the GT/AG rule. S-antigen genes in human and mouse were highly conserved. In contrast, genes for the Drosophila 49-kDa arrestin homolog and arrestin consist of three introns and four exons and two introns and three exons, respectively. The 5'-flanking region of the mouse S-antigen gene, approximately 1.0 kbp long, had no regulatory elements for transcription such as the TATA, CAAT and GC boxes, while a Drosophila arrestin gene has TATA and CAAT boxes. Interestingly, the 5'-flanking region of the mouse gene had promoter activity in an in vitro transcription assay using a nuclear extract of rat brain. A major transcription start site was found at 387 bp upstream from the translation start codon ATG in mouse. From our results, and those of others, we suggest that the S-antigen gene has evolved from a common ancestor gene by either insertion or deletion of introns. Such an alteration of gene structure may have played a role in the evolution of the S-antigen. PMID- 1879433 TI - Differential and specific labeling of epithelial and vascular endothelial cells of the rat lung by Lycopersicon esculentum and Griffonia simplicifolia I lectins. AB - In the rat lung, we found that the Lycopersicon esculentum (LEA) lectin specifically binds to the epithelium of bronchioles and alveoli whereas Griffonia simplicifolia I (GS-I) binds to the endothelium of alveolar capillaries. The differential binding affinity of these lectins was examined on semithin (approximately 0.5 microns) and thin (less than 0.1 (microns) frozen sections of rat lung lavaged to remove alveolar macrophages. On semithin frozen sections, LEA bound to epithelial cells lining bronchioles and the alveoli (type I, but not type II epithelial cells). On thin frozen sections, biotinylated Lycopersicon esculentum (bLEA)-streptavidin-gold conjugates were confined primarily to the luminal plasmalemma of type I cells. bGS-I-streptavidin-Texas Red was detected on the endothelial cells of alveolar capillaries and postcapillary venules but not on those of larger venules, veins or arterioles. By electron microscopy, GS-I streptavidin-gold complexes were localized primarily to the luminal plasmalemma of thick and thin regions of the capillary endothelium. Neither lectin labeled type II alveolar cells, but both lectins labeled macrophages in the interstitia and in incompletely lavaged alveoli. PMID- 1879434 TI - A comparison of the fibrinogen receptor distribution on adherent platelets using both soluble fibrinogen and fibrinogen immobilized on gold beads. AB - The distribution of fibrinogen receptors was determined on the surface of adherent platelets using both direct labeling with the ligand fibrinogen which was immobilized on gold particles (Fg-Au) and indirect immunogold (Ig-Au) labeling of bound soluble fibrinogen identified with a rabbit polyclonal anti fibrinogen antibody. Two distinctly different patterns of labeling were obtained and appeared to depend on whether solid phase fibrinogen (Fg-Au) or soluble phase released fibrinogen were bound to the membrane receptor. The membrane-bound Fg-Au reorganized in patterns that closely mimicked the organization of the underlying cytoskeleton. In approximately 18% of the adherent platelets, Fg-Au was seen in channels or vesicle-like structures lying deep to the platelet surface suggesting internalization into the open canalicular system and/or endocytosis. The labeling pattern obtained when identifying the location of membrane-bound soluble released fibrinogen by Ig-Au was diffuse and lacked the organizational patterns characteristic of Fg-Au. Unlike the Fg-Au probe, early dendritic platelets were heavily labeled by the soluble phase fibrinogen using the Ig-Au technique. Although the label covered the entire exposed platelet membrane in fully spread platelets, labeling over the peripheral web was more dense than that over the intermediate or granulomere zone. The diffuse organization and heavier peripheral distributional pattern of the glycoprotein IIb-IIIa (GP IIb-IIIa) receptor in fixed, adherent platelets, was also seen with the GP IIb-IIIa receptor-specific antibody AP-2. The binding of both the Fg-Au and Ig-Au were inhibited using the tetrapeptide Arg-Gly-Asp-Ser (RGDS) (93% and 98% inhibition, respectively), AP-2 (98% and 97%, respectively) and platelets from patients with Glanzmann's thrombasthenia (GT) (99% and 98%, respectively). The data presented provides the first report that receptor reorganization, following binding of fibrinogen, appears to be related to the state of the ligand. Substrate bound fibrinogen (i.e., Fg-Au or fibrinogen bound to another platelet) induces receptor translocation toward the platelet granulomere in a capping-like phenomenon. On the other hand, the binding of soluble released fibrinogen results in formation of microclusters and short linear arrays in a diffuse distribution but does not induce central movement of receptors. Furthermore, double labeling studies clarify that Fg-Au does not identify all available fibrinogen receptors as many are occupied by soluble released fibrinogen. The data presented provides an interesting new perspective on what constitutes an appropriate ligand-receptor stimulus sufficient to induce receptor reorganization. PMID- 1879435 TI - Adhesive interactions between fibroblasts and polymorphonuclear neutrophils in vitro. AB - Although the in vivo interaction between polymorphonuclear neutrophils (PMN) and fibroblasts may be important, these pathways have not been well studied. We have investigated the adherence of PMN to monolayers of human fetal lung fibroblasts, using a microtiter plate assay based upon the uptake by cells of the vital stain Rose Bengal. Stimulation with phorbol myristate acetate (PMA) caused a significant increase of adherence over basal levels which was rapid in onset and plateaued at 5 min. Adhesion was dependent on the leucocyte integrin family of glycoproteins, notably on Mac-1, since monoclonal antibodies toward the beta chain (CD18) and alpha chain (CD11b) of Mac-1 almost completely suppressed PMA induced PMN adhesion (88% and 77% inhibition, respectively). Adhesion was also inhibited by the peptides RGDS and GRGDS (24.2% and 26.6%, respectively using 1 mM peptide). Prestimulation of fibroblasts for longer time periods (5 and 24 h) with interleukin 1 alpha and tumor necrosis factor alpha, but not transforming growth factor beta, also resulted in a significant increase in adhesion of unstimulated PMN (after 24 h preincubation, 10 U/ml IL1 alpha stimulated adhesion by 179% of control, 500 U/ml TNF alpha by 157%). This indicated that there are both PMN- and fibroblast-dependent pathways for PMN adhesion. Components of the extracellular matrix of fibroblasts do not appear to play important roles in the adhesion process since addition of fibronectin and type IV collagen, or of purified antibodies to fibronectin and types I and IV collagen, did not affect PMA-induced PMN adhesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879436 TI - Differential response of cultured rabbit articular chondrocytes (RAC) to transforming growth factor beta (TGF-beta)-evidence for a role of serum factors. AB - We show that addition of TGF-beta (0.01-10 ng/ml) to proliferating rabbit articular chondrocytes in presence of low level of fetal calf serum (FCS, 2%) results in a sustained decrease of cell number and DNA synthesis up to 72 h. In contrast, incubation with high serum concentration (10% FCS) induces a transient increase of cell number after 48 h without elevation of DNA synthesis. Moreover, when the factor is added in 10% FCS-containing medium, a differential effect is observed at 48 h (either increase or decrease of cell number) depending on the serum level (2 or 10%) present between 24 and 48 h. Recruitment of cells in late S-phase occurred under TGF-beta-treatment in both 2 and 10% FCS. These arrested cells may then be released by further exposure to 10% FCS-containing medium. The data show that factor(s) from the serum modulate(s) the action of TGF-beta on chondrocyte proliferation. Addition of epidermal growth factor (EGF) to the cultures in presence of 2% FCS mimicks the effects observed with 10% serum, suggesting that the serum component(s) involved in the mechanism could be of EGF type. PMID- 1879437 TI - Conversion of a rabbit proximal convoluted tubule (PCT) into a cell monolayer: ultrastructural study of cell dedifferentiation and redifferentiation. AB - The evolution of a primary culture of kidney proximal convoluted tubule (PCT) cells was followed step by step from the plating time of an isolated tubule to the 39th day of culture. During the first 48 h, the structural remodeling of PCT, leading to the formation of a cell monolayer without cell division, is accompanied by intracytoplasmic changes indicating cell dedifferentiation. Numerous autophagic vacuoles are observed inside the cells, and the ultrastructural features characteristic of in situ PCT cells are progressively lost. Despite these drastic modifications, cell polarity, as observed by immunocytochemical detection of the leucine aminopeptidase, remains unaltered. Starting at 48 h, the peripheral cells divide, and the culture proliferates in a centrifugal direction while newly formed cells differentiate. From 6 days onwards, glycogen granules, never encountered in in situ PCT cells, appear in cultured cells and progressively accumulate. At the optimal stage of the culture (12-17 days old), cells somewhat resemble PCT cells, but their apical brush borders remain rudimentary, and basal cytoplasmic interdigitations surrounding densely packed mitochondria are poorly developed. Subsequently, the cells become overloaded with glycogen and lipid inclusions and resemble degenerating cells. PMID- 1879438 TI - The effects of estramustine on metaphase and anaphase in DU 145 prostatic carcinoma cells. AB - The chemotherapeutic drug, estramustine, has been shown to cause the disassembly of microtubules via binding to microtubule-associated proteins. In this report, estramustine is shown to be a potent inhibitor of mitotic progression in the human prostatic carcinoma cell line, DU 145. Examination of individual living cells via video-enhanced differential interference contrast (DIC) optics shows that the drug delays the onset of anaphase, reduces anaphase spindle-pole elongation (anaphase B), and delays cytokinesis. In addition, immunofluorescent studies demonstrate that estramustine causes a rapid disorganization of the mitotic apparatus at significantly lower concentrations than those reported previously. Electron microscopic studies show that microtubule bundles are present in drug-treated mitotic cells in association with kinetochores and centrioles. PMID- 1879439 TI - Microtubule polarity in Sertoli cells: a model for microtubule-based spermatid transport. AB - Bundles of microtubules occur adjacent to ectoplasmic specializations (ESs) that line Sertoli cell crypts and support developing spermatids. These microtubules are oriented parallel to the direction of spermatid movement during spermatogenesis. We propose a model in which ESs function as vehicles, and microtubules as tracks, for microtubule-based transport of spermatids through the seminiferous epithelium. Microtubule polarity provides the basis for the direction of force generation by available mechanoenzymes. As part of a more general study designed to investigate the potential role of microtubule-based transport during spermatogenesis, we have studied the polarity of cytoplasmic microtubules of Sertoli cells. Rat testis blocks were incubated in a lysis/decoration buffer, with and without exogenous purified bovine brain tubulin. This treatment results in the decoration of endogenous microtubules with curved tubulin protofilament sheets (seen as hooks in cross section). The direction of curvature of the hooks indicates microtubule polarity; that is, clockwise hooks are seen when viewing microtubules from the plus to the minus end. We found that, in Sertoli cells, most of the hooks were orientated in the same direction. Significantly, when viewed from the base of the epithelium, hooks pointed in a clockwise direction. The clockwise direction of dynein arms on axonemes of sperm tails, in the same section, provided an internal check of the section orientation. Electron micrographs of fields of seminiferous epithelium were assembled into montages for quantitative analysis of microtubule polarity. Our data indicate that Sertoli cell cytoplasmic microtubules are of uniform polarity and are orientated with their minus ends toward the cell periphery. These observations have significant implications for our proposed model of microtubule-based transport of spermatids through the seminiferous epithelium. PMID- 1879440 TI - Effects of daunomycin on the microtubular network: a cytochemical study on a human melanoma cell line. AB - The interaction of daunomycin (DAU), an anthracyclinic antibiotic employed as antitumoral agent, with microtubules, has been investigated by cytochemical and morphological methods on a human melanoma cell line (H14). Results obtained indicated that DAU was able to modulate the microtubule reassembly in cells treated with colcemid; such an effect proved to be dose-dependent. In particular, it has been observed that a low dose of DAU (0.05 microM) seemed to favor the microtubule reassembly whereas a higher dose (0.10 microM) impaired this process. In addition, when the anthracyclinic antibiotic was employed together with colcemid, both the cell detachment and the depolymerization of microtubules induced by the mitotic poison were hampered. These effects were dose-dependent and were better accomplished when DAU was used at an equimolar or at higher dose than that employed for the antimicrotubular agent. Moreover, the treatment of cells with DAU alone induced the stabilization of the microtubules, making them more resistant to the action of antimicrotubular agents. This effect could in part explain the antagonistic action exerted by DAU against colcemid. These observations seem to confirm that the microtubular network is an important target involved in the mechanism of action of the anthracyclinic antibiotics. PMID- 1879442 TI - The EEC and radiopharmaceuticals. PMID- 1879441 TI - Exocytosis in living salivary glands: direct visualization by video-enhanced microscopy and confocal laser microscopy. AB - Although exocytosis is widely believed to involve granule movement, membrane fusion and the emptying of granule content, direct study of these processes has been difficult in living cells because of the limited resolution of conventional light microscopy. Using video-enhanced microscopy and confocal laser microscopy, we have now studied these processes in living rat parotid and submandibular gland acinar cells. Under a differential interference contrast (DIC) microscope equipped with a CCD camera and a high speed image processor, secretory granules were in general stationary even after secretory stimulation with isoproterenol (IPR). Following IPR stimulation, however, there were abrupt changes in light intensity of secretory granules, and many granules disappeared. Confocal microscopy was then performed to confirm whether the observed changes in granules were related to membrane fusion and content release. For this, cells were perfused with the fluid-phase tracer Lucifer Yellow; confocal images thus obtained clearly demonstrated the appearance of fluorescence in omega-shaped invaginations of the apical plasma membrane which corresponded to the sites at which changes were observed in DIC images. The time sequence analyses of confocal images showed that there was a repetitive appearance and disappearance of omega shaped fluorescent foci at the apical plasma membrane until most of the granules were depleted. During this time, there did not appear to be any significant expansion of the apical plasma membrane and if endocytic uptake of the tracer occurred, it was below the limit of detection. These observations provide new insights into the exocytotic process in salivary glands and are at variance in some respects with previous interpretations made from electron microscopy. PMID- 1879443 TI - A method for measuring the absolute sensitivity of positron emission tomographic scanners. AB - A need exists to measure the absolute sensitivity of a positron emission tomographic (PET) scanner in units of counts.s-1.MBq-1. At present sensitivity is generally determined by measurement of a radionuclide of known concentration distributed in a water-filled cylindrical phantom, usually 20 cm in diameter. The measurement is confounded by self-attenuation of the source and scatter within the cylinder and does not give a true absolute sensitivity measurement. Due to variations in the magnitude and treatment of these factors, meaningful comparison between different manufacturer's scanners is difficult, as are comparisons between different acquisition geometries (e.g. with and without interplane septa present). A method has been developed in our laboratory that provides measurements of absolute sensitivity in air for a scanner independent of attenuation and scatter within the source. The method involves measurements of a thin-line source of fluorine 18 contained within an aluminium housing to which successive aluminium sleeves are added. The extrapolation of these measurements allows an effective counts.s-1.MBq-1 measurement to be made for zero thickness of aluminium. Measurements have yielded absolute sensitivities of 3926 +/- 61 counts.s-1.MBq-1 (0.39% efficiency), 5079 +/- 26 counts.s-1.MBq-1 (0.51%), and 32312 +/- 544 counts.s-1.MBq-1 (3.2%) for a whole-body PET scanner with interplane septa and for a NeuroPET operating with and without interplane septa, respectively. PMID- 1879444 TI - Technetium-99m carboxymethylcellulose: a newly developed fibre marker for gastric emptying studies. AB - We report a study of technetium-99m-labelled carboxymethyl-cellulose (99mTc-CMC) as a newly developed non-digestible marker of the solid phase of gastric contents. The radiosynthesis is simple and shows a high labelling efficiency. In vitro and in vivo experiments demonstrated stability of the marker in the gastrointestinal tract during the process of gastric emptying. The gastric half emptying time in ten healthy volunteers of both sexes was 105 +/- 17 min (mean +/ SD). This rate of gastric emptying is similar to that of non-digestible solid phase markers such as in vivo labelled 99mTc-chicken liver or radio-iodinated cellulose. In comparison with digestible solid-phase markers such as 99mTc labelled pancake or 99mTc-cooked egg, gastric emptying of 99mTc-CMC occurred more slowly, confirming the expected behaviour of a non-digestible solid-phase marker. We conclude that 99mTc-CMC has the advantage of a simple and rapid labelling procedure and may be useful for clinical studies of gastric emptying. PMID- 1879445 TI - Normalisation of glomerular filtration rate measurements. AB - The result of a glomerular filtration rate (GFR) measurement on a particular patient is of limited use to the referring physician since normal GFR values vary widely with the patient's age and build, etc. To overcome this problem, it is usual to normalise the measured GFR by dividing it by the patient's surface area and multiplying the result by the surface area of a 'standard' man. This transforms the measurement onto a scale which applies to all patients, young and old, large and small, where normal values fall within a well-defined range and where the degree of renal impairment can be quantified. We have examined the generally accepted surface area (SA) and the less well-known extracellular volume (ECV) normalisation methods of GFR measurements in a series of 110 patients. The results show that both methods produce essentially the same result; however, ECV normalisation is theoretically more correct, can be found directly without the patient's ECV being measured and does not require the use of empirical formulae. Mathematical justification for ECV normalisation is presented, and a proposed distribution pattern for the normalised measurement is introduced. A simple mathematical model shows that accurate GFR measurements can be made in the presence of an enlarged ECV, but normalisation of these will produce misleading low values. PMID- 1879446 TI - Comparison of technetium 99m polyclonal human immunoglobulin and technetium 99m monoclonal antibodies for imaging chronic osteomyelitis. First clinical results. AB - The accuracy of technetium-99m human immunoglobulin (HIG) for the detection of chronic osteomyelitis (OM) was compared with white blood cell scintigraphy using 99mTc-labelled monoclonal mouse antibodies (MAB). Seventeen patients suspected of having OM in 20 lesions went through three-phase skeletal scintigraphy, HIG scintigraphy and MAB scintigraphy. The final diagnosis was established by open surgery, histology and bacteriology. Chronic OM was proved in 14/20 lesions. Six of these 14 infections were located in peripheral areas without active bone marrow and 8/14 in central areas with active bone marrow. In peripheral OM, 5/6 with HIG and 6/6 with MAB were true positives. In the central skeleton all 8/8 infections appeared as cold lesions in the MAB study, which were defined as being false negative due to their non-specificity. Using HIG, 5/8 central infections were determined to be truly positive by showing photon-rich lesions. These 5 lesions were located in the hip region and in the pelvis, whereas 3 lesions of the spine were missed. There were no false-positive results in either studies. In conclusion, MAB was superior to HIG in peripheral OM concerning sensitivity, anatomical landmarks and differentiation of soft tissue versus bone infection. In central OM MAB detected all lesions accurately, but no differential diagnosis was possible due to the non-specificity of photon-low areas. In this respect HIG seems to be more specific due to the increased accumulation even in central infection sites. PMID- 1879448 TI - Importance of intra-therapy single-photon emission tomographic imaging in calculating tumour dosimetry for a lymphoma patient. AB - The dosimetry for two, similarly sized tumours in a lymphoma patient being treated with non-bone marrow ablative, monoclonal antibody therapy is reported. The 45-year-old man was infused with 2.48 GBq (67 mCi) of 131I-labelled MB-1. Prior to therapy, a time series of diagnostic conjugate-view images and a radionuclide transmission scan were obtained and processed to obtain time activity curves. Starting 2 days after the therapeutic infusion of radioactivity, a second conjugate-view time series was obtained. At that time, a quantitative single-photon emission tomography (SPET) acquisition was also carried out. Pre- and post-therapy X-ray computed tomography scans demonstrated a percentage reduction in volume for the right tumour which was 3.8 times that for the left tumour. In contrast, diagnostic conjugate views by themselves estimated the absorbed dose to be the same for the two tumours. Addition of therapy conjugate view data increased the right-over-left ratio but only to 1.22. Normalizing either time-activity series by the intra-therapy SPET results increased the ratio to greater than 1.5. We assume here that a differential dose is correct according to the differential tumour shirnkage. One can further assume that the largest ratio corresponds most certainly to the most accurate dosimetric method. Other assumptions are possible. While additional study is essential, data from this patient suggest that the preferred dosimetric method is intra-therapy SPET normalization of either time series. PMID- 1879449 TI - [25th meeting of the German Society for Electron Microscopy together with the DGE work groups cryo-electron microscopy, electron microscopic surface imaging and analysis, and scanning tunneling microscopy. Darmstadt, 1-7 September 1991. Abstracts]. PMID- 1879450 TI - Ninth meeting of the Italian Association for Cell Biology and Differentiation. Cefalu (Palermo), 30 September-3 October 1991. Abstracts. PMID- 1879447 TI - Radionuclide therapy revisited. AB - Apart from its use in endocrinology and rheumatology, therapeutic nuclear medicine is developing rapidly as an additional treatment modality in oncology. Many different specific tumour-seeking radiopharmaceuticals are being applied both for diagnostic scintigraphy and treatment, using multiple routes and mechanisms to target radionuclides at tumours. After a brief introduction of some basic principles of radionuclide targeting, the therapeutic radiopharmaceuticals available are reviewed according to the accumulation site in relation to the cell nucleus; the results of their current clinical use for therapy are also reviewed. The response observed to a number of these applications, the non-invasiveness of the procedure and the relative lack of toxicity and late effects in comparison with chemotherapy and external beam radiotherapy make radionuclide therapy an attractive and realistic alternative in the management of malignant disease, as well as in the treatment of a few benign disorders. PMID- 1879451 TI - Cold ischemic and reperfusion injury in a model of small bowel transplantation in the rat. AB - Following 0, 5, or 18 h of cold ischemia in the University of Wisconsin or Sacks' solution syngenic small bowel transplantation was performed to the renal vessels. Mucosal injury during ischemia or at reperfusion was evaluated microscopically using a grading scale from 0 to 8. The series subjected to small bowel transplantation without cold ischemia showed superficial damage to the tips of the villi (median grade 2) with no further exacerbation at reperfusion and complete healing 24 h thereafter. Moderate villous injury (median grade 3) was demonstrated following 5 h of cold ischemia. This injury was exacerbated to grade 4 (p less than 0.05) following reperfusion but was almost completely healed 24 h later. Grade 4 tissue injury was seen following 18 h of cold ischemia without further exacerbation at reperfusion and no clear tendency to healing 24 h later. PMID- 1879452 TI - Effects of thromboxane A2 synthetase inhibitor on postischemic liver injury in rats. AB - This study was designed to clarify the mechanism of a reversal of the ischemia induced decrease in adenosine triphosphate (ATP) in relation to the changes in liver blood flow. All vessels to the left and median lobes were occluded for 15 or 30 min and then reperfused for 15 or 30 min, respectively. Ischemia led to a significant decrease in the ATP level. ATP levels recovered fully after 30 min of reperfusion following 15 min of occlusion. However, a significantly low ATP level was observed even after 30 min of reperfusion following 30 min of occlusion. Premedication with CV-4151 (5 mg/kg, i.v.), a thromboxane A2 (TXA2) synthetase inhibitor, significantly improved the recovery of ATP levels after 30 min of reperfusion following 30 min of occlusion. Liver blood flow was restored fully immediately after reperfusion following 15 min of occlusion. In contrast a significantly low liver blood flow was observed after 30 min of reperfusion following 30 min of occlusion. Premedication with CV-4151 accelerated the recovery of liver blood flow after reperfusion. Morphological studies revealed that microthrombi were formed during ischemia, and CV-4151 mitigated the formation of microthrombi. These results indicate that the formation of microthrombi, which might be associated with TXA2 synthesis during ischemia, inhibited the restoration of liver blood flow, which might be responsible for the obstruction of the recovery of ATP. PMID- 1879453 TI - Energy metabolism of porcine liver during a 72-hour hypothermic perfusion with UW solution. AB - Porcine livers were preserved for 72 h using continuous hypothermic perfusion with UW solution and fluorocarbon emulsion (FC-43). They were then recirculated with human blood for 2 h at 37 degrees C for the evaluation of their viability. During hypothermic perfusion and recirculation, the main metabolites of the perfusate and adenine nucleotide concentrations were measured in order to examine the energy metabolism of the livers. This study revealed that hypothermically perfused livers, which mainly utilize endogenous fatty acids as an energy substrate during this time were adequately preserved for 72 h. In terms of energy metabolism, it is suggested that when using the method of continuous hypothermic perfusion with UW solution and FC-43, the administration of adequate amounts of certain fatty acids might prolong the preservation period. PMID- 1879454 TI - Partial replacement of the oesophageal muscle layers by a carbon-fibre prosthesis. AB - In the present study we report on the surgical replacement of the thoracic portion of oesophageal muscularis by a synthetic carbon fibre (CF) prothesis in a rabbit model. Our results, as corroborated by the oesophagograms and the post operative weight gain, showed that this prothesis functioned satisfactorily for up to 6 weeks observation period. When the observation period was extended to 12 and 24 weeks after surgery, dilatation of the oesophagus at the prosthetic site was observed. All animals tolerated this dilatation and survived their intended observation period in good condition. In all these animals the body weight loss of -11.23 +/- 3.97% (p = 0.005) noted during the 1st week after the operation stopped and the body weight returned to its preoperative level within 3 weeks, as in the control groups. When the CF protheses were wrapped with a non biodegradable polyurethane ether material with an elasticity of 19.2 g/mm, all rabbits died within 3 weeks or had to be sacrificed because of complications due to stagnation of food. In these rabbits the body weight decreased dramatically by -27.40 +/- 5.41% (p less than 0.001). In any similar future studies using the rabbit model, the post-operative body weight should provide a simple, sensitive and reliable monitoring tool for the functional assessment of the reconstructive procedure. PMID- 1879455 TI - Effect of local hemostatics on platelet aggregation. AB - The platelets play an important role in the normal hemostasis, and it is known that both natural and synthetic macromolecules may induce platelet activation and aggregation. Thus, the purpose of the present study was to investigate the platelet aggregating effect of five different local hemostatics. Platelet aggregation was assessed by aggregometry. Unwoven fleece of bovine collagen polymer in fibrillar form induced aggregation in combination with small amounts of platelet agonists; ADP and adrenaline. Ordinary, nonabsorbable bone wax also induced aggregation in combination with the agonists, but larger concentrations of agonists were needed. Bioerodible polyorthoester with physical properties such as bone wax, oxidized cellulose and gelatin sponge did not promote platelet aggregation. PMID- 1879456 TI - A new surgical model of acute liver failure in the pig: experimental procedure and analysis of liver injury. AB - In this research, the effects of portocaval shunt plus 70% partial hepatectomy were evaluated in 11 pigs. Hepatic coma and death from progressive liver failure occurred in 5 pigs between 14 and 64 h from surgery, whereas 3 pigs, which also showed symptoms of progressive liver failure, died of presumed gastric hemorrhage between 17 and 19 h after surgery. In 3 pigs, transient liver failure was followed by complete recovery, as judged by clinical, electroencephalographic and biochemical parameters. No case of death occurred among the pigs treated with portocaval shunt alone or 70% partial hepatectomy alone as controls. This new model for acute liver failure is reproducible, seems to be potentially reversible, causes death due to hepatic failure after a time period sufficiently long to allow for the institution of support procedures, is applied to a large animal and lacks relevant biohazard. Therefore, this model may be used to evaluate possible support procedures during acute liver failure. PMID- 1879457 TI - Effects of long-acting superoxide dismutase on liver metabolism after major hepatic resection in rats with cirrhosis. AB - The aim of this study is to clarify the liver metabolic changes after major hepatic resection. The survival rate after 70% hepatectomy of rats with cirrhosis was significantly depressed compared with that of the control group. Mitochondrial function in the cirrhotic liver was disturbed compared with the control group. Tissue levels of hypoxanthine and xanthine increased both in the cirrhotic group and the control group. The increase in xanthine levels was remarkable and was prolonged in the cirrhotic group compared with the control group. Decreases in adenine nucleotides were observed after resection both in normal and cirrhotic livers. These were remarkable and were prolonged in rats with cirrhosis. Administration of polyoxyethylene-modified superoxide dismutase improved the survival rate and lessened decreases in adenine nucleotide levels. Moreover, it accelerated the recoveries of serum glutamic oxaloacetic and pyruvic transaminase levels after resection in rats with cirrhosis. These results indicate that disturbances in energy metabolism and increases in oxygen free radical formation are more remarkable in the cirrhotic liver than in the normal liver, which contributes to a low survival rate in rats with cirrhosis. PMID- 1879458 TI - Early indicators of allograft rejection in a porcine pancreatic transplantation model. AB - Urine cytology and blood lymphocyte blastogenesis were evaluated as indicators of allograft rejection in a porcine pancreatic transplantation model. The percentage of activated lymphocytes and/or blasts was significantly increased during the rejection phase. Positive cytology was present in all rejection episodes. An increased thymidine uptake of blood lymphocytes and a decreased uridine/thymidine uptake quotient were seen prior to the onset of rejection. The reported dissociation of anionic and cationic trypsin levels in serum and urine after transplantation was not seen after simple urinary diversion of the pancreatic juice. This supports the hypothesis that a decreased synthesis of cationic trypsinogen compared with anionic trypsinogen occurs after porcine pancreatic transplantation. PMID- 1879459 TI - Interaction of mianserin, amitriptyline and haloperidol with guinea pig cerebral histamine H2 receptors studied with [125I]iodoaminopotentidine. AB - Tricyclic antidepressants were previously shown to potently inhibit the histamine induced activation of H2 receptors linked to adenylate cyclase in cerebral membranes, and this effect was postulated to represent the mechanism of their therapeutic activity. However, these drugs were found to be much less potent (up to more than hundred-fold) at H2 receptors mediating cyclic AMP responses in intact cells. We have presently assessed whether this large difference in potency of antidepressants, also observed with haloperidol, results from a modified pharmacological specificity of the H2 receptor according to the medium composition. We have studied the binding of [125I]iodoaminopotentidine (125I-APT) to striatal or hippocampal membranes under various experimental conditions. At equilibrium the Kd of 125I-APT, a highly selective ligand for H2 receptors, was six times higher in a supplemented Tris buffer used for adenylate cyclase assays in cell-free systems than in a Krebs-Ringer medium used in studies with intact cells. The medium composition also variously affected the Ki values of the four compounds studied amitriptyline, mianserin, haloperidol and tiotidine. Whereas the Ki value of amitriptyline was little affected, that of the other compounds was four to five times lower in the supplemented Tris buffer than in the Krebs Ringer medium. With the exception of tiotidine, the Ki values of other compounds in the binding test performed in this medium, were intermediate between those derived from the antagonism of histamine-induced cyclic AMP responses in membranes and intact cells. These data indicate that the difference between the two test responses is diversely attributable to several factors according to the compounds, the main ones being medium composition and possibly cell disruption. PMID- 1879460 TI - Chronic mianserin treatment decreases 5-HT2 receptor binding without altering 5 HT2 receptor mRNA levels. AB - Rats were injected with 15 mg/kg (i.p.) mianserin or vehicle (saline) for 4, 10 or 21 days and 5-HT2 receptor binding and mRNA levels measured. Treatment with mianserin induced a substantial decrease in 5-HT2 radioligand binding (44-59% decrease; P less than 0.05 vs. control). No changes in the amount of 5-HT2 or, as a control, beta-actin mRNAs were found (P greater than 0.05 vs. control). These results indicate that mianserin decreases 5-HT2 radioligand binding without altering steady-state 5-HT2 mRNA levels. PMID- 1879461 TI - Quisqualate and carbachol-induced increases in intrasynaptosomal free calcium are mediated by different products of phospholipid hydrolysis. AB - The mechanisms by which quisqualate and carbachol increase intrasynaptosomal free calcium ([Ca2+]i) were studied in rat cortical synaptosomes. Quisqualate (0.01 100 microM) and carbachol (100-1000 microM) increased [Ca2+]i in Fura-2 acetoxymethyl ester (Fura-2 AM)-loaded synaptosomes. The resting level of [Ca2+]i was 118 nM. The maximum increase (55%) was produced by 10 microM quisqualate which had an EC50 of 0.2 microM. The maximum increase (28%) elicited by carbachol occurred at 1000 microM and the EC50 was 30 microM. The stimulatory effects of quisqualate on [Ca2+]i were blocked by heparin (100 I.U.) but not by staurosporine (1 microM), nifedipine (1 microM) or omega-conotoxin fraction GVIA (omega-CgTx) (0.5 microM). On the other hand, the effects of carbachol on [Ca2+]i were abolished by staurosporine, nifedipine or omega-CgTx but not by heparin. Carbachol (100 microM) also significantly increased 45Ca accumulation into either resting or K+ (30 mM)-depolarised synaptosomes and these effects were inhibited by staurosporine and nifedipine. Quisqualate (10 microM) had no effect on 45Ca accumulation under resting or depolarised conditions. When quisqualate and carbachol were used in combination, there were apparently additive effects on [Ca2+]i but not on 45Ca accumulation. It is concluded that carbachol increases [Ca2+]i by facilitating Ca2+ entry through L-type Ca2+ channels via a 1,2 diacylglycerol (DAG)-protein kinase C (PKC)-dependent pathway while quisqualate mobilizes Ca2+ from inositol 1,4,5-trisphosphate (IP3)-sensitive stores. PMID- 1879462 TI - DNA strand break metabolism in human lymphocytes: a reevaluation. AB - Recent findings concerning the presumed existence of single-strand breaks (SSB) in quiescent human peripheral blood lymphocytes (PBL) are discussed in relation to the role of poly(ADP-ribosyl)ation in DNA strand break metabolism. It is argued that the activation of poly(ADP-ribose)polymerase (ADPRP) by a DNA damaging agent is not indicative of an obligatory role of poly(ADP-ribosyl)ation in DNA repair. From this it follows that SSB induced by different strand-breaking agents might be removed by either ADPRP-dependent or ADPRP-independent DNA repair pathways. PMID- 1879463 TI - Effects of type-beta 1 transforming growth factor on the proliferation and differentiation of mouse myelomonocytic leukemia cells (M1). AB - Murine myelomonocytic leukemia M1 cells have been used to examine the effects of type-beta 1 transforming growth factor (TGF-beta 1) on cellular proliferation and differentiation in monocyte-macrophage lineage. TGF-beta 1 inhibited immature M1 cell growth due to a general slowdown of the cell cycle, without arrest at any specific point. Ten nanograms per milliliter TGF-beta 1 completely suppressed phagocytic activity and adhesion to the dish surface and partially inhibited the expression of Fc receptors and vimentin during the differentiation of M1 cells induced by IL-6. IL-6-induced declines in the expression of c-myc mRNA and in the accumulation of G0/G1 cells were also partially blocked by TGF-beta 1. When treated concurrently with IL-6 and TGF-beta 1, approximately 50% of M1 cells were morphologically converted to promonocyte or monocyte-like cells, which did not exhibit the characteristics of mature macrophages. Although pretreatment with TGF beta 1 also inhibited the IL-6-induced phagocytic activity, this inhibition was reversible. Once TGF-beta 1 was removed from the culture medium after 72 h of incubation with IL-6, the kinetics of differentiation induced by IL-6 were faster in pretreated cells than in nonpretreated cells. TGF-beta 1 appears to inhibit the IL-6 induced conversion of M1 cells at the intermediate stage of monocytic differentiation. PMID- 1879464 TI - Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor. AB - Effect of hepatocyte growth factor (HGF) on normal human epidermal keratinocytes cultured under conditions of low Ca2+ (0.1 mM, growth-promoting condition) and physiological Ca2+ (1.8 mM, differentiation-promoting condition) was investigated. In low Ca2+, HGF markedly enhanced the migration of keratinocytes while it suppressed cell growth and DNA synthesis in a dose-dependent manner. In contrast, HGF enhanced the migration, cell growth, and DNA synthesis of keratinocytes cultured under conditions of physiological Ca2+. The maximal stimulation of DNA synthesis (2.4-fold stimulation) in physiological Ca2+ was seen at 2.5-5 ng/ml HGF and the stimulatory effect of HGF was suppressed by transforming growth factor-beta 1. Analysis of the HGF receptor using 125I-HGF as a ligand showed that human keratinocytes expressed a single class of specific, saturable receptor for HGF in both low and physiological Ca2+ conditions, exhibiting a Kd = 17.3 pM and approximately 690 binding sites/cell under physiological Ca2+. Thus, HGF is a potent factor which enhances growth and migration of normal human keratinocytes under conditions of physiological Ca2+. HGF may play an important role in epidermal tissue repair as it enhances both the migration and growth of keratinocytes. PMID- 1879465 TI - 4-Hydroxynonenal reduces junctional communication between endothelial cells in culture. AB - The effect of 4-hydroxynonenal (HNE), a lipid peroxidation product, on junctional communication (JC) among cultured vascular endothelial cells was assessed by both study of the transfer of microinjected 6-carboxyfluorescein between neighboring cells and measurement by a "cut-loading and dye transfer" technique. Both methods indicated that at concentrations higher than 10(-9) M and testing times between 6 and 8 h HNE reduces endothelial cell junctional communication. At 10(-8) M, a gradual development of HNE effect appears during 6-8 h of exposure but is followed by a slow recovery completed at 20 h. The reduction in junctional communication is not produced by the inhibition of protein synthesis, as tested by radiolabeled leucine incorporation. The HNE effect might be relevant to pathological processes in which lipid peroxidation is associated with uncontrolled cell proliferation, as in atherogenesis and promotion of carcinogenesis by chronic inflammation. PMID- 1879466 TI - Both cross-links and monoadducts induced in DNA by psoralens can lead to sister chromatid exchange formation. AB - The relative importance of DNA-DNA cross-links and bulky monoadducts in sister chromatid exchange (SCE) formation was investigated in three human fibroblast cell lines with different repair capabilities. These cell lines included normal cells, which can repair both classes of lesions; xeroderma pigmentosum (XP) cells, which cannot repair either psoralen-induced cross-links or monoadducts; and an XP revertant that repairs only cross-links and not monoadducts. SCEs were induced by two psoralen derivatives, 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT) and 5-methylisopsoralen (5-MIP). After activation with long-wave ultraviolet light, HMT produces cross-links and monoadducts in DNA, whereas 5-MIP produces only monoadducts. In normal human cells both psoralens induced SCEs, but if cells were allowed to repair for 18 h before bromodeoxyuridine (BrdUrd) was added for SCE analysis, the SCE frequency was significantly reduced. XP cells showed an SCE frequency that remained high regardless of whether SCEs were analyzed immediately after psoralen exposure or 18 h later. In the XP revertant that repairs only cross-links, both psoralens induced a high yield of SCEs when BrdUrd was added immediately after psoralen treatment. When XP revertant cells were allowed 18 h to repair before addition of BrdUrd, the SCEs induced by HMT were greatly reduced, whereas those induced by 5-MIP were only slightly reduced. These observations indicate that both cross-links and monoadducts are lesions in DNA that can lead to SCE formation. PMID- 1879467 TI - TGF beta elicits opposite responses in clonal subpopulations of NRK-49F cells. AB - Clonal subpopulations of NRK-49F cells were isolated and characterized for their responses to transforming growth factor beta (TGF beta). Two fibroblastic clones, N1 and N4, were found to have opposite TGF beta responses. TGF beta inhibits EGF induced proliferation in growth-arrested, subconfluent monolayer cultures of N1 but not N4 cells. In contrast, TGF beta stimulates DNA synthesis and an increase in cell number in N4 but not N1 cells. The inhibitory effect of TGF beta on DNA synthesis in N1 cells is due not to modulation of the EGF receptor or other early G1 events. EGF-induced myc mRNA accumulation is not inhibited, and the action point for TGF beta inhibition of the entry into S of N1 cells is at the G1-S boundary. PMID- 1879468 TI - Comparative effects of cytosine arabinoside and a prostaglandin E2 antagonist, AH6809, on chondrogenesis in serum-free cultures of chick limb mesenchyme. AB - The present study was designed to compare effects of an established inhibitor of cell proliferation and growth, cytosine arabinoside (Ara C), with that of a prostaglandin E2 (PGE2) antagonist, AH6809, on chondrogenesis in cultured mesenchyme derived from stage 25 chick limb buds. Continuous treatment of cell cultures with 10(-4) M AH6809 prevented completely the twofold increases in DNA content of control cultures which occurred between Day 1 and Day 5 of culture and also produced 90% inhibition of chondrogenesis occurring in control cultures during this same period. Treatment of cells with Ara C (0.1-0.5 microgram/ml) produced equivalent inhibition of DNA content during the same time period; however, chondrogenesis, as evaluated on Day 5 of cell culture, remained at approximately 90% of control cultures. These results indicate that the inhibitory effect of PGE2 receptor blockade on cell growth in these cultures cannot account for the potent inhibitory effects observed on differentiation of cartilage and provide further evidence in support of the notion that PGE2 plays an important initiating role in the process of chondrocyte differentiation within limb mesenchyme. PMID- 1879469 TI - Effects of sodium butyrate on the rearranged c-myc expression in mouse plasmacytoma cells. AB - The expression of c-myc mRNA was examined after 4 h of sodium butyrate treatment in a mouse plasmacytoma (MPC) cell line (S194). Steady-state levels of rearranged c-myc mRNA were suppressed by the agent in S194 cells. Run-on assay demonstrated that the suppression of the rearranged c-myc mRNA in the MPC was correlated with the transcriptional downregulation of the gene. The suppression was also accompanied by the reduced DNase I sensitivity of the gene. These findings suggest that the rapid downregulation of c-myc mRNA by sodium butyrate is subject to regulation at the transcriptional level following the alteration of the DNase I sensitive chromatin structure in mouse plasmacytoma cells. PMID- 1879470 TI - Restoration of daunomycin retention in multidrug-resistant P388 cells by submicromolar concentrations of SDZ PSC 833, a nonimmunosuppressive cyclosporin derivative. AB - Overexpression of P-glycoprotein may cause increased efflux of a variety of anticancer drugs (ACD) leading to multidrug resistance (MDR) of tumor cells. Two sublines of murine monocytic leukemia P388 cells were used, one parental (Par P388) and one multidrug resistant (MDR-P388). In cell growth inhibition assays in vitro, the Par-P388 cells showed a normal sensitivity to daunomycin (DAU) while the MDR-P388 cells were 200-fold resistant. In cellular fluorescence assays, DAU retention in MDR-P388 cells reached only 5% of the level achieved in Par-P388 cells. This cell line pair was used to compare the nonimmunosuppressive cyclosporin analog PSC 833 with several resistance-modifying agents (RMAs) for their in vitro chemosensitizing activity and for their restoration of DAU retention. PSC 833 sensitized the MDR-P388 cells 60- and 140-fold when used at 0.1 and 0.3 micrograms/ml (0.08 and 0.25 microM), respectively, a complete restoration of sensitivity being obtained at 1.0 micrograms/ml PSC 833. Similarly as little as 0.1 micrograms/ml (0.08 microM) PSC 833 was sufficient to restore intracellular DAU retention to 60% of the level found in Par-P388 cells, a 3-fold higher concentration restoring virtually the whole DAU retention. For both these activities, PSC 833 was at least one order of magnitude more active than CsA, which was itself an order of magnitude stronger than verapamil, another RMA already used in clinic. Since PSC 833 had no effect on the PAR-P388 cells, neither on chemosensitization nor on drug retention, it is assumed that it acts on the P-glycoprotein, which is highly expressed on the membrane of the MDR-P388 cells, by inhibiting the function of the P-glycoprotein pump and thus restoring a normal ACD-sensitivity of the MDR-P388 cells. PMID- 1879471 TI - Mammary organoids from immature virgin rats undergo ductal and alveolar morphogenesis when grown within a reconstituted basement membrane. AB - We have recently described a primary culture system which allows for extensive proliferation and functional differentiation of immature mammary epithelial cells. Herein, these findings are extended to demonstrate that a distinct pattern of ductal and alveolar morphogenesis can be induced within the mammary organoids isolated from virgin female rats and cultured within an Engelbreth-Holm-Swarm sarcoma-derived reconstituted basement membrane under defined serum-free conditions. The lobular and multilobular organoids that emerged resemble the alveoli of the mammary gland in gross form, multicellular architecture, and cytologic and functional differentiation, while the ductal organoids expressed characteristics typical of mammary gland ducts in vivo. The epithelial cells within the alveolar- and duct-like organoids displayed the capability of secreting two morphologically distinct milk products, casein and lipid, into the luminal compartment. The expression of histiotypic morphogenesis and mammary specific functional differentiation by the cultured mammary organoids proceeded in the absence of a morphologically distinct basal lamina. We illustrate that development highly reminiscent of that which naturally occurs in the mammary gland in vivo can be induced and supported in vitro under defined serum-free conditions. In addition, the methodologies are available to simultaneously monitor mammary organoid morphogenesis, growth, and functional differentiation. This system should serve as a unique model in which the regulation of branching morphogenesis, development, gene expression, and transformation can be examined. PMID- 1879472 TI - Inhibition of murine melanoma cell-matrix adhesion and experimental metastasis by albolabrin, an RGD-containing peptide isolated from the venom of Trimeresurus albolabris. AB - Albolabrin, a 7.5-kDa cysteine-rich protein isolated from the venom of Trimeresurus albolabris, contains the arginine-glycine-aspartic acid (RGD) cell recognition sequence found in many cell adhesion-promoting extracellular matrix proteins, such as fibronectin and laminin. Albolabrin belongs to a family of RGD containing peptides, termed disintegrins, recently isolated from the venom of various vipers and discovered to be potent inhibitors of both platelet aggregation and cell-substratum adhesion. Here we report that albolabrin inhibited the attachment of B16-F10 mouse melanoma cells to either fibronectin or laminin absorbed on plastic. When immobilized on plastic, albolabrin promoted B16 F10 melanoma cell attachment; this was inhibited by either RGD-serine (RGDS) or antibodies to integrins, suggesting that albolabrin binds via its RGD amino sequence to integrin receptors expressed on the melanoma cell surface. In an in vivo experimental metastasis system, albolabrin at a concentration of 300-600 nM inhibited C57BL/6 mouse lung colonization by tail vein-injected mouse melanoma cells and was at least 2000 times more active than RGDS in this assay. We propose that albolabrin inhibits tumor cell metastasis by inhibiting integrin-mediated attachment of melanoma cells to RGD-containing components of the extracellular matrix in the mouse lung. PMID- 1879473 TI - Laminin synthesized by stationary and migrating rat liver epithelial cells lacks the A chain. AB - The expression of laminin chains was analyzed in normal and Ha-ras1-transformed rat liver epithelial cells. The normal, nontumorigenic cells were induced to migrate by epidermal growth factor, whereas the Ha-ras1-transformed, malignant derivatives migrate constitutively. None of these cells express a typical (EHS like) laminin A chain. Immunoprecipitation of [35S]-methionine-labeled liver cell lysates with an antibody against EHS-laminin revealed B1 and B2 chains and, in addition, two high Mr polypeptides. These polypeptides were not recognized by the antibody in immunoblots, suggesting that they might constitute alternative laminin A chains. Analysis of the expression of all three laminin chains at the RNA and protein level revealed that the pattern of expression of the stationary cells does not differ from that of the migratory ones and is also not influenced by epidermal growth factor. These results indicate that expression of a typical laminin A chain by rat liver epithelial cells is not required for the secretion and deposition of the protein in the extracellular matrix. The data also indicate that an EHS-like laminin A chain is not required for the migration of these epithelial cells. PMID- 1879474 TI - Expression of carbohydrate binding protein 35 in human fibroblasts: variations in the levels of mRNA, protein, and isoelectric species as a function of replicative competence. AB - We have compared the expression and localization of carbohydrate binding protein 35 (CBP35) in human SL66 fibroblasts of different replicative capacities. When serum-starved, quiescent young (passage 11, corresponding to approximately 18 cumulative population doublings) SL66 cells were treated with serum, there was a marked stimulation in the expression of CBP35. This was revealed both by an increase in the percentage of cells positively stained with anti-CBP35 under immunofluorescence and by an increase in the amount of the protein in immunoblots, as well as by an increase in the level of accumulated mRNA in Northern blots. The rise in the expression of CBP35 in proliferating cells was manifested most clearly in the nuclear fraction, with elevation in the levels of the nonphosphorylated (pI8.7) protein, as well as the phosphorylated (pI8.2) derivative. In contrast, older (passage 27-35, 55-68 cumulative population doublings) cultures of SL66 fibroblasts appear to have lost the normal proliferation-dependent regulation of CBP35 expression. The level of CBP35 was high in quiescent high-passage cells and decreased somewhat after serum stimulation. Furthermore, the unphosphorylated (pI 8.7) form of the lectin could not be detected in either the nucleus or the cytoplasm of high-passage SL66 cells. Finally, the level of the mRNA for CBP35 was high in quiescent cultures of high-passage cells, but undetectable 17 h after serum stimulation. These results establish that the expression of CBP35 becomes altered as human fibroblasts acquire reduced replicative capacity. PMID- 1879475 TI - Nonradioactive, sequence-specific detection of RNA in situ by primed in situ labeling (PRINS). AB - A new method for the detection of RNA in situ is presented. It is based on sequence-dependent annealing of unlabeled specific oligonucleotide primers to intracellular RNA and subsequent chain elongation catalyzed by reverse transcriptase. Under the conditions described, biotin-labeled nucleotides can be incorporated and the cDNA synthesized in situ can thus be detected using fluorescein-conjugated avidin. Compared to traditional in situ hybridization the use of short oligonucleotide primers has the potential advantage of being better to discriminate between closely related RNA transcripts. Compared to in situ transcription with radioactive precursors we find it more attractive to use fluorescein-conjugated avidin as detection system because it allows a more detailed study of cell and signal simultaneously. PMID- 1879476 TI - Congenital cataract following German measles in the mother. 1941. PMID- 1879477 TI - Laboratory diagnosis of rubella: past, present and future. PMID- 1879478 TI - A longitudinal study of natural infection of piglets with Streptococcus suis types 1 and 2. AB - Streptococcus suis types 1 and 2 were detected in nasal swabs taken from five litters of piglets sampled twice weekly from birth. The two types had been detected in all pigs by the time they were 38 and 25 days old respectively with mean ages of first detectable infection being 13.5 and 8.5 days. The prevalence of infection was not affected by housing conditions or the population density of pigs. Piglets originating from a sow with vaginal swabs positive for S. suis type 2 were infected earlier than piglets from non-vaginal carriers. It is concluded that infection of piglets with S. suis type 2 may occur during the birth process. PMID- 1879479 TI - Incrimination of an environmental source of a case of Legionnaires' disease by pyrolysis mass spectrometry. AB - Following a case of Legionnaires' disease Legionella pneumophila of the same serogroup was isolated from the hot water system of the hotel which had been epidemiologically implicated as the source of the infection. Pyrolysis mass spectrometry (PyMS) was used to compare 11 isolates from the hotel water sample with the patient's strain. Epidemiologically unrelated isolates, both clinical and environmental, of the same serogroup and monoclonal antibody type of L. pneumophila were included in the same analysis, together with relevant reference strains. The patient strain was shown to be indistinguishable from seven of the hotel water isolates, but clearly different from other unrelated clinical isolates, the reference strains and some of the other environmental isolates. PyMS is a rapid and cheap method for inter-strain comparison for L. pneumophila. PMID- 1879480 TI - An outbreak of Legionnaires' disease in Gloucester. AB - Fourteen people living in or near the city of Gloucester fell ill with Legionnaires' disease caused by Legionella pneumophila serogroup (SG) 1 between 27 August and 27 October 1986. Another patient had fallen ill on 30 May. Nine of the 15 were diagnosed retrospectively during a case finding exercise. There were three deaths. Three cases of Pontiac fever were also diagnosed. The source was probably one or more wet cooling towers. Nineteen premises in the city with such towers were identified, and three just outside Gluocester. Samples from 11 of the 22 premises grew Legionella spp.; from nine of these L. pneumophila SG 1 (Pontiac) was isolated. The efficacy of regular addition of biocide in addition to hypochlorite added at the time of disinfection in inhibiting the growth of Legionella spp. was demonstrated. A survey of patients' movements during their likely incubation period showed that there was no single building that all patients had visited, but there were two areas of the city which nearly all had visited or passed through by car. A case-control study demonstrated an association with one of these areas. Cooling towers near both areas may have been sources but the evidence is insufficient to incriminate any single one. The unexpected finding of L. pneumophila SG 1 (Pontiac) in nine towers supports the hypothesis that there may have been multiple sources. Cooling towers may have been contaminated by mains water or by drift from other towers. PMID- 1879481 TI - Antigens recognized by the human immune response to severe leptospirosis in Barbados. AB - Serum samples obtained from patients hospitalized in Barbados with severe leptospirosis were tested by the microscopic agglutination test (MAT), enzyme immunoassay (EIA) and immunoblotting with leptospires that had been isolated from these patients. While serum samples taken a few days after onset of symptoms often showed no apparent correlation between MAT and EIA, later sequential serum samples produced similar profiles in both tests during the course of infection. Immunoblotting sonicate from Leptospira interrogans serovars arborea, copenhageni and bim with patients' sera, revealed reactions with a number of bands that corresponded with outer envelope components. These components included lipopolysaccharide (LPS), flagella and other outer membrane proteins, in addition to a low-molecular-weight (MW) carbohydrate cross-reactive with members of the Leptospiraceae. IgM antibodies elicited in the first to second week after infection reacted mainly with LPS and the low-MW cross-reactive carbohydrate. Comparative analysis of isolates of the same serovar by sodium dodecyl sulphate polyacrylamide gel electrophoresis and immunoblotting showed that while two serovar arborea isolates were identical, serovar bim isolates differed significantly from each other. This difference was also observed in comparative MAT testing. PMID- 1879483 TI - Cockroaches (Blattella germanica) as carriers of microorganisms of medical importance in hospitals. AB - A study was conducted to isolate and identify microorganisms of medical importance from cockroaches (Blattella germanica) and to ascertain their vector potential in the epidemiology of nosocomial infections. Bacteria, fungi and parasites of medical importance were isolated and identified. Important bacterial pathogens responsible for wound infections, were further studies by antibiograms. One hundred and fifty-eight out of 159 (99.4%) cockroaches collected from hospital (test) and 113 out of 120 (94.2%) cockroaches collected from residential areas (control) were carrying medically important microorganisms (P less than 0.05). significantly higher (P less than 0.001) number of test cockroaches were carrying a higher bacterial load (1 x 10(4) and 1 x 10(5] as compared to control cockroaches. Multiple drug-resistant bacterial were isolated from test cockroaches. The diversity of drug-resistant bacterial species isolated from test cockroaches suggests their involvement in the transmission of drug-resistant bacteria. Various fungi and parasitic cysts of medical importance were also isolated from the test and control cockroaches, but the carriage rates were low. The findings suggest that cockroaches, in hospitals, can act as potential vectors of medically important bacteria/parasites/fungi. PMID- 1879482 TI - Rubella vaccines: past, present and future. PMID- 1879484 TI - The prevalence of Salmonella enteritidis and other Salmonella sp. among Canadian registered commercial chicken broiler flocks. AB - A nation-wide survey was conducted to estimate the prevalence of Salmonella enteritidis and other salmonellas among Canadian commercial broiler flocks. Environmental (litter and/or water) samples from 226 of 294 (76.9%) randomly selected flocks were contaminated with salmonellas. Litter samples were more often contaminated with salmonellas than water samples (47.4 v. 12.3%). Fifty different salmonella serovars were isolated. The most prevalent serovars were S. hadar, S. infantis, and S. schwarzengrund; they were isolated from samples of 98/294 (33.3%), 26/294 (8.8%), and 21/294 (7.1%) flocks, respectively. Feed samples of 39/290 (13.4%) flocks were contaminated with salmonellas. Salmonella enteritidis was isolated from the environmental samples of 9/294 (3.1%) flocks. Salmonella enteritidis phage type (PT) 8 was isolated from seven flocks, and PT 13a from two flocks. PMID- 1879485 TI - Gentamicin-resistant Salmonella typhimurium phage type 204c: molecular studies and strain diversity in a putative bovine outbreak. AB - As part of the investigation of a putative bovine outbreak, 13 isolates of Salmonella typhimurium phage type 204c were subjected to plasmid analysis. Plasmid profiles suggested that several distinct strains were involved and these observations were supported by minor variations in antibiotic resistance pattern. Restriction enzyme fingerprinting and conjugational segregation of the plasmids confirmed these findings. Although 12 of the 13 isolates were resistant to gentamicin, resistance was conferred by 4 distinct plasmids; 3 of these belonged to Inc I and were distantly related on the basis of restriction fingerprints and the fourth was a resistant derivative of the 60 MDa S. typhimurium serotype specific plasmid. The molecular evidence refuted the hypothesis that geographical and temporal clustering of these gentamicin-resistant isolates could be explained on the basis of a single epidmiological episode. PMID- 1879486 TI - Genetic diversity among toxigenic and nontoxigenic Vibrio cholerae O1 isolated from the Western Hemisphere. AB - Multilocus enzyme electrophoresis was used to examine genetic relationships among and between toxigenic and non-toxigenic isolates of Vibrio cholerae O1 obtained from patients and the environment in the US Gulf Coast and surrounding areas. A total of 23 toxigenic and 23 non-toxigenic strains were examined. All the toxigenic and 7 of the non-toxigenic strains had the same alleles at 16 enzyme loci, whereas the balance of the nontoxigenic strains had 9 distinct combinations of alleles. This study suggests that all of the toxigenic strains belong to a single clone, and that while some of the non-toxigenic isolates were related, most were of diverse origin. PMID- 1879487 TI - The isolation of Listeria species from fresh-water sites in Cheshire and North Wales. AB - We report a study to determine the presence of Listeria species in surface waters. One hundred ml volumes of 30 water samples taken from 21 different sites were analysed. Most of the samples examined were from ponds and lakes. Listeria species were isolated on eight (27%) occasions, six of these isolates were L. seeligeri, one was L. innocua and one L. welshimeri. Although not statistically significant, coliform and Escherichia coli counts were higher in waters that were positive than were negative for Listeria spp. It is suggested that the low isolation rate of listeria in this study reflects the fact that most waters examined did not receive sewage outfalls. Water sports activities are unlikely to be a risk factor for listeriosis. PMID- 1879488 TI - Rubella in the United Kingdom. PMID- 1879489 TI - Rubella in Europe. PMID- 1879490 TI - Rubella in the United States: toward a strategy for disease control and elimination. PMID- 1879491 TI - Rubella in the developing world. PMID- 1879492 TI - Civil war and the spread of AIDS in Central Africa. AB - Using ordinary least squares regression techniques this paper demonstrates, for the first time, that the classic association of war and disease substantially accounts for the presently observed geographical distribution of reported clinical AIDS cases in Uganda. Both the spread of HIV 1 infection in the 1980s, and the subsequent development of AIDS to its 1990 spatial pattern, are shown to be significantly and positively correlated with ethnic patterns of recruitment into the Ugandan National Liberation Army (UNLA) after the overthrow of Idi Amin some 10 years earlier in 1979. This correlation reflects the estimated mean incubation period of 8-10 years for HIV 1 and underlines the need for cognizance of historical factors which may have influenced current patterns of AIDS seen in Central Africa. The findings may have important implications for AIDS forecasting and control in African countries which have recently experienced war. The results are compared with parallel analyses of other HIV hypotheses advanced to account for the reported geographical distribution of AIDS in Uganda. PMID- 1879493 TI - A large outbreak of gastroenteritis associated with a small round structured virus among schoolchildren and teachers in Japan. AB - In March 1989 a large outbreak of acute gastroenteritis occurred simultaneously among schoolchildren and teachers at nine elementary schools in Toyota City, Japan. Illness was observed in 3236 (41.5%) of 7801 schoolchildren and 117 (39.4%) of 297 teachers. The main clinical symptoms were diarrhoea, vomiting, nausea and abdominal pain. Gastroenteritis was significantly associated with the consumption of school lunch served by one particular lunch preparation centre. One food handler at the centre suffered from gastroenteritis during the outbreak. Small round structured virus (SRSV) was detected in 4 of 8 stool specimens from sick persons. The school lunch contaminated by the infected food handler is the most probable source of this outbreak due to SRSV. PMID- 1879494 TI - Actin filaments in the photoreceptor cilium of the rds mutant mouse. AB - An actin filament meshwork was recently demonstrated within the ciliary axoneme at the base of the photoreceptor outer segment (OS) in rat retina. Individual filaments of a uniform polarity extended from the cilium and entered into the bottom of the OS disc stack where they associated with the plasma membrane in the region of new disc assembly. This and other studies have indicated that an actin mediated mechanism may regulate OS disc morphogenesis. The homozygous rds mouse exhibits an absence of OS formation, although cilia do develop and opsin is contained within the ciliary plasma membrane. The rds abnormality is believed to result from a defect in OS disc assembly. Immunogold labeling has shown that actin is situated within the distal end of rds photoreceptor cilia, as well as in the distal cilium of normal mice prior to the onset of OS differentiation. However, anti-actin antibodies do not distinguish between monomer and filamentous actin. In the current study, neural retinas from rds and control mice were permeabilized with saponin, incubated with myosin subfragment-1 (S-1), and prepared for electron microscopy. Following this treatment, a meshwork of myosin S-1 decorated actin filaments could be observed within the axoneme in the distal end of each rds photoreceptor cilium. As in normal visual cells, actin filaments exited the axoneme by passing between pairs of microtubule doublets. These filaments had the correct polarity, with all arrowheads pointing toward the axoneme, and they associated with the ciliary plasma membrane in the region where OS disc morphogenesis would normally occur. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879495 TI - Temporary impairment of Muller cell metabolism in the rat retina by intravitreal injection of fluorocitrate. AB - Fluorocitrate was injected in the vitreum of rats in order to define the experimental conditions for a temporary impairment of Muller cell metabolism in the retina. Injection of 16 nmol of fluorocitrate appeared to fulfil this requirement since this dose resulted in a large decrease in retinal endogenous glutamine and a smaller decrease in glutamate within 6 hr of administration. The reversible nature of the effect was attested by a substantial recovery of the retinal levels of the two amino acids within 24 hr of injection. In vitro experiments of carbon incorporation from different substrates, carried out with retinas dissected from eyes previously injected with fluorocitrate, were consistent with a metabolic impairment of glial cells, since carbon incorporation from [14C]acetate into glutamine was almost completely abolished in the fluorocitrate-treated retinas. Electron microscopic examination in fluorocitrate poisoned retinas demonstrated essentially selective ultrastructural alterations of Muller cells at times corresponding to their maximal metabolic impairment. Since Muller cells are by far the largest glial population of the rat retina, common astrocytes being only scattered in the nerve fibre layer, the present experimental model may be used to study the role of Muller cells in the metabolism of retinal neurotransmitters. PMID- 1879496 TI - Glutathione and related indices in rat lenses, liver and red cells during riboflavin deficiency and its correction. AB - Biochemical changes in lenses and at other sites in adult rats were investigated during the induction and correction of riboflavin deficiency. Riboflavin deficient (D), 1-day-repleted (R1), 2-days-repleted (R2), 16-days-repleted (R3), food-restricted, weight-matched controls (CFR) and ad libitum-fed controls (CAL) were compared. Activation coefficients of erythrocyte and lens glutathione reductase, which became abnormal in the deficient (D) animals, were corrected to varying extents in the repleted (R) groups. Hepatic flavin concentrations were lowered in the groups with raised glutathione. Inter-group differences in hepatic glutathione concentrations were not simply related to tissue flavin depletion or its reversal, but were complicated by changes in liver: body-weight ratios. Inter group differences in lenticular glutathione levels were very small. In both liver and lens, sorbitol concentrations were lowest in group R3 and highest in groups D, R1 and R2. Lens ascorbate levels and the lens enzymes, aldose reductase, sorbitol dehydrogenase, glutathione peroxidase and superoxide dismutase, were not significantly affected by diet. Thiobarbituric acid-reactive substances were increased in riboflavin-deficient rat lenses but were lowered in riboflavin deficient plasma samples. The results suggest overall that while riboflavin deficiency may affect certain biochemical indices, such as sorbitol and thiobarbituric-reactive substances, in the lens and other tissues, these changes are not the result of lowered glutathione levels. They also clearly demonstrate the importance of inanition as a confounding factor in the interpretation of changes resulting from riboflavin deficiency in experimental animals. PMID- 1879497 TI - Insulin and IGF-I binding in developing chick neural retina and pigment epithelium: a characterization of binding and structural differences. AB - We have characterized insulin and insulin-like growth factor I (IGF-I) binding sites in developing chick retina and pigment epithelium (10- and 14-day embryonic, and 2-week post-hatched). For comparison, binding sites in brain and liver were also examined. Both the retina and pigment epithelium (PE) contain separate, specific, high affinity binding sites for insulin and IGF-I. In both tissues, IGF-I binding exceeds insulin binding by two to threefold. Insulin and IGF-I binding in the retina is four to six times greater than in PE. Insulin and IGF-I binding in the retina and PE exhibit independent developmental regulation. In the retina, the number of binding sites decreases by approximately 50% between embryonic day 10 and 2 weeks post-hatching. In the PE, binding decreases slightly between embryonic day 10 and 14 and then, in the 2-week post-hatched chick, increases threefold. Insulin receptor binding subunits in the retina and brain are similar in that both are neuraminidase insensitive and have apparent molecular weights of 116 kD. In contrast, binding subunits in the PE and liver have higher molecular weights (about 126 kD), and are sensitive to neuraminidase. At the embryonic stages examined, the levels of retinal insulin and IGF-I binding exceed those of the brain by five to 13-fold. Taken together, these data suggest that the retina is a major target of insulin and IGF-I and that the binding of these growth factors is developmentally regulated. PMID- 1879498 TI - One member of the gamma-crystallin gene family, gamma s, is expressed in birds. PMID- 1879499 TI - Age-dependent changes in resistivity and electrolytes related to lens development and growth in the rat. AB - Alterations in resistivity measurements of lens homogenates, lens percent water and cation concentrations of sodium and potassium show a complex pattern in the Sprague-Dawley rat during lens development and maturation. During the neonatal period, the data provide evidence for three distinct periods: days 5-12, a pre critical maturation period (pre-CMP), a steep decline in cation concentration and a minimal change in percent water were accompanied by an expected sharp rise in resistivity; days 12-16, critical maturation period (CMP), a further decrease in ion concentration and water was concomitant with the unexpected observation of no significant change in resistivity; and days 16-30, post-CMP, no significant changes were observed for cation concentrations, percent water, or resistivity. From 30 to 100 days, an adult nuclear maturation period (NMP), a decrease in cation concentration and percent water was reflected in a rise in resistivity. A comparison of 100 and 500 day lenses revealed that the concentrations of Na and K, and percent water are essentially unchanged. The K/Na ratio, which had decreased from an initial value of 5.9 at 5 days, stabilized at approximately 4 by day 100. A comparison of the resistivity measured in both lens homogenates and KCl solutions at identical molar strengths revealed that, for the ages studied, ion concentration and ion mobility play important roles in determining this parameter. The underlying cause for age related variations in lens susceptibility to cataractogenic insult is most likely related to complex changes in composition and resistivity which undoubtedly reflect adjustments in molecular organization. The proposition that the lens is a 'free flowing' syncytium of cells appears unwarranted. PMID- 1879500 TI - The 1990 Endre Balazs Lecture. Effects of some neuropeptides on the uvea. AB - This lecture summarizes studies on the effects of some of the neuropeptides which seem to be present in somatosensory and autonomic nerves in the uvea. Release of these peptides is likely to explain nerve induced effects in the eye which are not due to classical transmitters. Trigeminal nerve fibres in the eye seem to contain substance P (SP), calcitonin gene-related peptide (CGRP), and cholecystokinin (CCK), parasympathetic nerve fibers from the facial nerve seem to contain vasoactive intestinal polypeptide (VIP), and peptide with histidine and isoleucine terminals (PHI), and sympathetic nerves seem to contain neuropeptide Y (NPY). Retrograde trigeminal nerve stimulation in rabbits causes hyperemia, miosis, a breakdown of the blood-aqueous barrier to plasma proteins and a rise in intraocular pressure (IOP). There is release of SP and CGRP or related peptides. The miosis seems to be due to SP and the other effects to CGRP and small amounts of arachidonic acid metabolites released by the peptides. SP has no miotic effect in monkeys and cats. However, CCK is a potent miotic in monkeys and causes contraction of the human pupillary sphincter muscle. It has no such effect in the lower species. The effect of CCK in primates seems to derive from the presence of CCK receptors of the A-type on the pupillary sphincter muscle, and can be blocked by lorglumide. Miosis can be produced in cats by the peptide endothelin; this effect is due to release of arachidonic acid metabolites. Facial nerve stimulation causes vasodilation in the uvea of rabbits, cats and monkeys. The effect cannot be abolished by muscarinic blocking agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879501 TI - Comparative histogenesis of Bruch's membrane (complexus basalis). AB - We documented the comparative histogenesis and timing of development of Bruch's membrane (complexus basalis) in five mammalian models with different lengths of gestation. Retinas with attached choroid from the central posterior pole of the eye were obtained from hamster, vole, rabbit, ferret and cat, from mid-gestation onward until the time at which all components of Bruch's membrane could be detected. The sequence of events in the development of Bruch's membrane was similar among species, however the time of appearance of the components varied. At mid-gestation, the basement membrane of the retinal pigment epithelium (RPE) was present to some degree in all species and microfibrils were developing in the connective tissue space external to the RPE basement membrane. The appearance of an initially scant endothelial basement membrane around the choriocapillaries occurred on post-natal (P) day 1 (P1) in hamster, pre-natal (E) day 20 (E20) in vole, E16 in rabbit, P2 in ferret, and E48 in cat. Among the microfibrils within the connective tissue space external to the RPE, electron-dense islands presumed to be elastin were detected on P7 in hamster, P9 in vole, E24 in rabbit, P19 in ferret, and P1 in cat. Relative to birth date and eye opening, the components of Bruch's membrane in the ferret were detected at a later date than that of the other species studied. However, relative to the interval from conception to the appearance of the components of Bruch's membrane, the ferret and cat are similar, paralleling their similar intervals from conception to eye opening. PMID- 1879502 TI - Development of light-evoked changes of the interphotoreceptor matrix in normal and RCS rats with inherited retinal dystrophy. AB - The interphotoreceptor matrix (IPM) has recently been shown to undergo a change in distribution following the transition between light and dark [IPM light response: Uehara et al., (1990 b) Science 248, 1633-36]. In the present study, the development of light-evoked IPM changes has been examined histochemically in the retinas of normal and Royal College of Surgeons (RCS) rats with inherited retinal dystrophy between the ages of post-natal day (P) 12 and 40. In normal rats at P12 and P14, the IPM was uniformly and intensely stained with the colloidal iron reaction in both light- and dark-adapted retinas. The capacity of the IPM to undergo the light-evoked distributional change shown previously in adults appeared between P14 and P16. At P16 and older ages, the IPM in light adapted rats was concentrated in bands at the apical and basal regions of the outer segment zone, whereas the IPM remained uniformly stained in dark-adapted rats. In RCS rats, the light-evoked change developed at the same age as in normal rats, although it was lost between P20 and P25. Correlations of the time of onset and loss (in RCS rats only) of the light-evoked IPM distributional change with other developmental events suggest that mature, organized photoreceptor outer segments are necessary for the IPM light response to occur, and that in RCS rats the disruption of the IPM light response may contribute to the characteristic accumulation of IPM in the basal outer segment zone and photoreceptor cell death in this form of retinal degeneration. PMID- 1879503 TI - Interaction and aggregation of lens crystallins. AB - Crystallins of the normal eye lens have a specific structure that maintains lens transparency. This structure reportedly arises from a short-range order. The age related post-translational changes and high molecular weight (HMW) aggregation disrupt the normal structure and decrease lens transparency. In the current study, we have carried out fluorescence measurements (polarization and extrinsic probe binding) in an attempt to understand protein interaction and aggregation. Based on polarization measurements of dansyl chloride (DCl) labeled gamma crystallin, there is a hetero-interaction among crystallins (alpha-gamma, beta gamma, etc.) but no self-interaction in gamma-crystallin (gamma-gamma) (less than 30 mg ml-1). Alpha-crystallin is rich in hydrophobic region and possibly has a self-interaction through hydrophobic interaction. Hydrophobic probes, ANS (1 anilinonaphthalene-8-sulfonic acid) and DPH (1,6-diphenyl 1,3,5-hexatriene) measurements show that alpha-crystallin is a very hydrophobic protein. HMW alpha crystallin appears to be even more hydrophobic, indicating that the post translational unfolding exposes more hydrophobic groups which facilitate HMW aggregation. The HMW aggregation results from highly hydrophobic proteins which tend to become thermodynamically more stable. PMID- 1879504 TI - The effect of white light exposure on the rabbit eye lens as measured by fluorophotometry and spectrophotometry. AB - Fluorophotometry and spectrophotometry of the rabbit lens were performed after white light exposure to detect possible changes in the lens before damage could be seen by biomicroscopic slit lamp examination. In nine rabbits the lens of one eye was exposed to white light and that of the fellow eye was used as a control. The incident light power was 240 mW for 90 min on a lenticular area of 3 mm2. Slit lamp examination of lens and cornea prior to, 1 hr after and 2 days after light exposure did not reveal any sign of damage. The mean in vivo autofluorescence ratio between exposed lens and non-exposed fellow lens was found to increase significantly from 1.0 +/- 0.08 S.D. (n = 9) before exposure to 3.3 +/- 0.8 S.D. (n = 9; P less than 0.004) 1 hr after exposure and hereafter to decay exponentially with a half time of 0.8 days to the ratio before exposure (correlation coefficient: -0.97, P = 0.0013). Three additional rabbits were exposed as described above with subsequent in vitro spectrophotometry of the lenses between 400 and 800 nm revealing an absorbance peak at 468 nm with a half width of 10 nm. The ratio between the absorbance peak of exposed lens and non exposed fellow lens was found to increase from 1.1 before exposure to 2.8 1 hr after exposure and then to decrease to 1.4 at 1 day after exposure. The corresponding autofluorescence ratios measured in vivo before spectrophotometry were 0.93, 2.6 and 1.5, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879505 TI - Identification of prostaglandins and hydroxyeicosatetraenoic acids in kitten retina: comparison with other species. AB - Conversion of arachidonic acid to eicosanoids by kitten retinae was investigated to evaluate whether the pattern of kitten retinal eicosanoids simulates that found in the human and other animal species. Freshly isolated kitten retinae were incubated with 20 microM radiolabeled arachidonic acid, and the metabolites were analysed by reverse phase-high pressure liquid chromatography, thin-layer chromatography and gas chromatography-mass spectroscopy. Kitten retinal tissues converted arachidonic acid into prostaglandins (PGs), thromboxane (Tx) and hydroxyeicosatetraenoic acids (HETEs). The major eicosanoid identified was 6kPGF1 alpha--the stable non-enzymatic hydrolysis product of prostacyclin. Other eicosanoids identified included TxB2, PGE2, PGF2 alpha, 12-hydroxy heptadecatrienoic acid, 12-HETE, and 15-HETE. The spectrum of kitten retinal cyclooxygenase metabolites is similar to those obtained from bovine retina and human retinal vascular endothelium with prostacyclin being the major cyclooxygenase metabolite produced. PMID- 1879506 TI - Glycation-induced crosslinking of calf lens crystallins. AB - To investigate the possible role of glycation in the onset of diabetic cataract we used calf lens crystallins as a model. After incubation with reducing sugars, the proteins were investigated by high-pressure gel permeation chromatography, SDS-PAGE and analytical ultracentrifugation. Glucose-6-phosphate incubation resulted in an increase in mean molecular weight of all crystallin fractions and the occurrence of high-molecular weight material, partly formed by disulphide bonds. The glycated crystallins showed a decrease of tryptophan fluorescence and an increase of a specific non-tryptophan fluorescence. This fluorescence was, however, not exclusively associated with the high molecular weight protein, but was present in all protein fractions. PMID- 1879508 TI - Immune reactions against rabies viruses--infection and vaccination. PMID- 1879507 TI - Thrombin is a stimulator of retinal pigment epithelial cell proliferation. AB - Two preparations of bovine thrombin were found to stimulate DNA synthesis in cultured human retinal pigment epithelial cells. DNA synthesis was assessed by both [3H]thymidine incorporation into TCA precipitable material and nuclear labeling with [3H]thymidine. Cultures grown in the presence of thrombin for 48 hr showed a significant increase in cell number. When the concentrations of the two thrombin preparations were normalized for clotting activity, they had almost identical dose-response curves and both caused a tenfold maximal stimulation of [3H]thymidine incorporation. The EC50 for the preparation with higher specific activity was 20 ng ml(-1). Hirudin, a specific high affinity inhibitor of thrombin, completely blocked the mitogenic effect. When a maximally effective concentration of thrombin was used in combination with maximally effective concentrations of other growth factors (insulin, acidic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor), they were found to be strongly synergistic in stimulating DNA synthesis. These data suggest that thrombin may act as an endocrine mediator of retinal pigment epithelial cell proliferation and participate in normal and exaggerated ocular wound healing. PMID- 1879509 TI - A comparative study of cultured vascular and lymphatic endothelium. AB - There is comparatively little knowledge of the structure and function of cultured lymphatic endothelium. A study was carried out to compare the intrinsic growth characteristics of cultured lymphatic endothelial cells with cultured endothelial derived from blood vessels. It was found that cultured lymphatic endothelium has growth requirements and growth characteristics similar to vascular endothelium. It also possesses FVIIIRA and Weibel-Palade bodies for specific identification. The results of this study have provided important base line data for subsequent studies of the pathobiology of lymphatic endothelium. PMID- 1879510 TI - Nephrotoxic effects of diethylene glycol (DEG) in rats. AB - Diethylene glycol (DEG) is a widely used substance with various risks of intoxication. In adult rats influences of DEG on functional parameters are characterized, indicating early signs of nephrotoxicity. A dose dependent proteinuria, an oliguric effect, an increased excretion of free hydrogen ions and a compensated impairment of renal tubular transport processes can be stated (0.25, 0.5 and 0.75 ml DEG/100 g b.m. i.p.). Following a single dose of 0.5 ml DEG/100 g b.m. i.p. the maximally expressed nephrotoxic effect is measurable 4 to 8 days after administration. PMID- 1879511 TI - Blood histamine level in rabbits experimentally immunized with soluble elastin. AB - Experimental immunization of rabbits with soluble porcine elastin was performed. An increase in histamine level in blood of immunized animals was observed. PMID- 1879512 TI - The diabetogenic and acidotropic effects of chelators. AB - Diabetogenic and acidotropic effects of dithizone, 8-(p-toluenesulfonylamino) quinoline and 8-(benzenesulfonylamino)-quinoline were studied in experiments on cats, rabbits, golden hamsters and mice. Selective damage of insulin producing cells, phase glycemic fluctuations and permanent diabetes development were shown to be connected with chelator zinc binding in the lysosome-segregation apparatus of these cells. PMID- 1879513 TI - Gap junctional vesicles in the neointimal smooth muscle cells of balloon injured carotid artery. AB - After balloon injury of the carotid artery in the rat, gap junctional vesicles were frequently detected in neointimal smooth muscle cells. They represent spherical structures confined by pentalamellar membrane containing a fine filamentous and granular material inside. Since gap junctional vesicles are not typical for the medial smooth muscle cells their occurrence in the intimal cells may be related to their secretory function and/or proliferative capacity. PMID- 1879514 TI - Influence of vasoactive substances on uremic bleeding in rats. AB - Bleeding time is prolonged following resection of kidney tissue as well as after ureteral occlusion. Bilateral nephrectomy raises bleeding time from 17 to 67 min, and blood loss can be increased from 2 to 12 microliters/min. Plasmatic coagulation factors remain unchanged in uremic rats. There is no influence of various surgical interventions producing uremia on function of thrombocytes. In rats with intact kidney function and following bilateral nephrectomy a diminution of bleeding time is demonstrable after administration of histamine or captopril. Shortening of bleeding time by the antifibrinolytic substance p aminomethylbenzoic acid seems to indicate an increased fibrinolytic activity in uremic rats. PMID- 1879515 TI - Elastin and collagen content in the aorta of rabbits experimentally immunized with soluble elastin. AB - Experimental immunization of rabbits with soluble porcine elastin was performed. A statistically significant decrease in the level of insoluble elastin in the aorta of the immunized animals was observed. Estimations of soluble collagen fractions showed the rise of both salt-soluble and acid-soluble collagen in the aorta of rabbits immunized with soluble porcine elastin. PMID- 1879516 TI - Leptospiral antigens (L. interrogans serogroup ictero-haemorrhagiae) in the kidney of experimentally infected guinea pigs and their relation to the pathogenesis of the renal injury. AB - The search for leptospiral antigens (L. interrogans serogroup icterohaemorrhagiae) was carried out in 24 guinea pigs experimentally inoculated with 1 ml of culture containing 10(7)-10(8) leprospires and sequentially sacrificed from the first until the 6th day of infection. Semiquantitative analysis of histopathological variables comprising kidney interstitium, tubules and glomeruli was done in 1 micron sections of tissue embedded in glycolmetacrylate. Leptospiral antigen (LAg) and its glycolipoprotein (GLP) expression were detected through PAP in paraffin embedded tissue. The mild interstitial involvement of the kidney, manifested chiefly by oedema and focal interstitial nephritis seen at the 4th day, progressed to tubular damage at the 6th day, characterized by either swelling or cytoplasmic acidophilia of epithelial cells with loss of cell cohesion and sloughing of cells into the tubular lumina. Brush border alterations and mitochondrial changes were observed. Endothelial cell injury was noted in the interstitial vessels. LAg expression was parallel to the kidney changes: small deposits of elongated forms of LAg were detected at the 4th day either within the vascular lumen or free in the interstitium. A rise in the antigen expression was observed at the 5th day when it was seen either around tubules or in their walls. LAg was detected inside the tubular lumina at the 6th day of infection when granular LAg and GLP were abundant. This sequence reproduces the pathway of leptospires in the kidney and the crescent amounts of antigens detected toward the end of the experiment, with antigen concentration in cases of major tissue damage suggesting a direct action of the microorganisms and/or their products in the pathogesis of the lesions. PMID- 1879517 TI - Lead induced ultrastructural changes in the testis of rats. AB - Oral lead administration (250 ppm lead acetate through drinking water) to weaning male rats for 70 days resulted in the marked accumulation of this metal in blood and testicular tissue. No marked changes were evident in light microscopy. Ultrastructural changes were revealed in the form of vacuolisation of Sertoli cell cytoplasm and increase in the number and size of lysosomes. Some of the vacuoles contained vesicle like structures. Although there was no impairment of spermatogenesis, the changes in the Sertoli cells may lead to changes in spermatogenesis after chronic exposure. PMID- 1879518 TI - The potency of amide protons for assignments of NMR spectra of carbohydrate chains of glycoproteins, recorded in 1H2O solutions. AB - Three glycoprotein N-glycans, namely, a disialylated diantennary carbohydrate chain linked to Asn, a monosialylated, fucosylated diantennary glycopeptide with bisecting N-acetylglucosamine, and a tetrasialylated, fucosylated tetra-antennary oligosaccharide, have been investigated by two-dimensional NOE and HOHAHA spectroscopy in 1H2O as solvent. The amide protons of all N-acetylglucosamine and sialic acid residues could readily be assigned. The large chemical-shift dispersion of the amide resonances of the N-acetylglucosamine residues, allowed the unambiguous assignment of every N-acetyl methyl signal, via strong NOEs. Subspectra could be obtained of all N-acetylglucosamine residues in HOHAHA spectra. These results have as main implication that several biologically important large glycans will now [corrected] become amenable for conformational studies by multidimensional NMR in 1H2O solution. PMID- 1879519 TI - Localization of surface peptide from ribosomal protein L7 on 80 S ribosome by biotinylation. AB - A surface topography of ribosomal peptides on ribosome particles was conducted by using N',Hydroxysuccinimido-biotin (NHS-biotin) modification. All rat ribosomal proteins, except proteins L3 and L8, are biotinylated when the ribosome particle is the substrate. A surface peptide from protein L7 was determined from biotinylated ribosomes by high performance liquid chromatography and cyanogen bromide peptide mapping. It was found that only the tandem repeats of the NH2 terminal segment of protein L7 are accessible to biotinylation. It is concluded that the NH2-terminal-end of protein L7 should be exposed on the surface of ribosomal particles. PMID- 1879520 TI - Geometry of binding of the N alpha-tosylated piperidides of m-amidino-, p-amidino and p-guanidino phenylalanine to thrombin and trypsin. X-ray crystal structures of their trypsin complexes and modeling of their thrombin complexes. AB - The X-ray crystal structures of the complexes formed with bovine trypsin and the N alpha-tosylated piperidides of m-amidino-, p-amidino- and p-guanidino-D,L phenylalanine (3-TAPAP, 4-TAPAP and 4-TGPAP) were determined with data to 1.8 A resolution. The L-stereoisomer of 3-TAPAP binds as a compact entity into the active site of trypsin, with the amidino and the carbonyl groups of the central amidinophenylalanyl residue hydrogen-bonded to Gly216 of trypsin. According to modeling and energy minimization, 3-TAPAP fits perfectly in this conformation to the more restrictive thrombin active site also (Bajusz et al. (1978) Int. J. Pept. Prot. Res. 12, 217-221); the piperidine moiety extends into the cage-like S2 subsite of thrombin, but leaves room for additional substituents which might help to improve binding and pharmacological properties. In contrast, 4-TAPAP and 4-TGPAP bind only weakly and in an extended conformation to trypsin; their considerably enhanced affinities for thrombin would suggest a more compact binding to thrombin. PMID- 1879521 TI - The role of lipid peroxidation products in cumene hydroperoxide-induced Ca2+ efflux from mitochondria. AB - Cumene hydroperoxide-induced calcium release from mitochondria has been studied. Activation of lipid peroxidation by increasing concentrations of cumene hydroperoxide does not enhance calcium efflux induced by low (up to 50 microM) concentration of cumene hydroperoxide. It is concluded that cumene hydroperoxide induced calcium release depends mainly on processes coupled to hydroperoxide reduction by an endogenous enzyme system. PMID- 1879522 TI - Dynamics of the excited state of the primary electron donor in reaction centers of Rhodopseudomonas viridis as revealed by hole burning at 1.7K. Different conformational states. AB - The spectra of absorbance changes (delta A) due to the formation of P+Q- (P, primary electron donor, Q, primary quinone acceptor) at 1.7K in Rhodopseudomonas viridis reaction centers (RCs) excited at 1014 nm has been shown to include, besides a progression of broad (170-190 cm-1) Gaussian vibronic bands separated by 150 cm-1, a 'narrow' structure near 1014 nm which can be simulated by a Lorentian zero-phonon hole (ZPH) and Lorentian one-mode (26.8 cm-1) phonon wings. The widths of ZPH of approximately 17 cm-1 for delta A reflecting the formation of P+Q- decaying in the ms time domain and of 6.8 +/- 0.4 cm-1 for P+Q- decaying in the min time domain at 1.7K, seems to correspond to different conformations of RCs with a relaxation time of P* of approximately 0.6 ps (in agreement with measurements in this time domain) and 1.6 +/- 0.1 ps, respectively. The comparison of the spectra of delta A in the region of the BL band for slow (min) and fast (ms) decaying components suggests a different mutual arrangement of P and BL for different conformations of RCs. It is assumed that the broad and narrow structures of the P band reflect the transitions to two configurations with different P-protein interactions. 'Narrow' structure of delta A spectrum with essentially the same phonon wings and ZPH (width of 3.8 +/- 0.4 cm-1) was observed within the P band when HL was photoreduced at 1.7K. PMID- 1879523 TI - Evolutionary origin of numerous kringles in human and simian apolipoprotein(a). AB - Human apolipoprotein(a) has a great size heterogeneity and consists of 38 kringle domains in the amino terminal and a serine protease domain in the carboxyl terminal. All but one kringle of apolipoprotein(a) are homologous to the fourth kringle of plasminogen. However, the 38th kringle resembles the fifth kringle of plasminogen and its seems to have been deleted in simian species. The phylogenetic trees suggest that an ancestral apolipoprotein(a) may have started with a duplicate of a plasminogen type protein. It also implies that deletion of the three kringles in the amino terminus followed, and that one of the remaining two kringles was duplicated in both human and simian species and the other was processed by a deletion in simian species after species separation. Thus, the number of kringles in other mammals not yet studied may vary considerably from species to species. PMID- 1879524 TI - O-H stretching vibration in Fourier transform difference infrared spectra of bacteriorhodopsin. AB - FTIR difference spectroscopic studies of M intermediate and LA bacteriorhodopsin in the O-H stretching region show bands at 3671 and 3641 cm-1, respectively. The O-H stretching bands in this region may reflect protonation-deprotonation changes or environmental change in the tyrosine residues in bR. PMID- 1879525 TI - Inhibition of aspartic proteinases by propart peptides of human procathepsin D and chicken pepsinogen. AB - Two propart peptides of aspartic proteinases, the propart peptide of chicken pepsin and human cathepsin D, respectively, were investigated from the point of view of their inhibitory activity for a set of aspartic proteinases. These peptides display a very broad inhibitory spectrum. The strongest inhibition was observed for pepsin A-like proteinases where propart peptides can be used as titrants of active enzymes. PMID- 1879526 TI - Crystallographic investigations of the tryptophan-derived cofactor in the quinoprotein methylamine dehydrogenase. AB - A model of tryptophan tryptophylquinone (TTQ), recently proposed by McIntire et al. (Science (1991) 252, 817-824) to be the prosthetic group of the quinoprotein methylamine dehydrogenase, has been compared with electron density maps of this dehydrogenase from Thiobacillus versutus and Paracoccus denitrificans. The comparison shows that the TTQ model can be neatly accommodated, providing strong supportive evidence that TTQ is indeed the cofactor for this group of quinoproteins. PMID- 1879527 TI - Purification and characterization of E37, a major chloroplast envelope protein. AB - We have purified to homogeneity E37, the second major polypeptide of the inner membrane of the chloroplast envelope. The protein was retained on a Mono S column at pH 7, indicating it is a basic protein. After cyanogen cleavage, the protein was partially sequenced at 2 different sites. The sequence is compared with the deduced amino acid sequence of a cDNA coding for a 37 kDa envelope polypeptide recently published by Dreses-Werringloer et al. (Eur. J. Biochem. (1991) 195, 361 368.) PMID- 1879528 TI - Induction of differentiation of human leukemia cells by inhibitors of myosin light chain kinase. AB - Inhibitors of myosin light chain kinase, 1-(5-chloronaphthalene-1-sulfonyl)-1H hexahydro-1,4-diazepine hydrochloride (ML-9) and 1-(5-iodonaphthalene-1-sulfonyl) 1H-hexahydro-1,4-diazepine hydrochloride (ML-7), induced Nitroblue tetrazolium reducing activity, lysozyme activity and morphological maturation of human monoblastic U937, THP-1 and promyelocytic HL-60 cells, but not of erythroblastic K562 cells. However, three analogs of ML-9, which are an inhibitor and an activator of protein kinase C, and a calmodulin antagonist, respectively, did not induce differentiation of the cells. PMID- 1879529 TI - Uniform labeling of a recombinant antibody Fv-fragment with 15N and 13C for heteronuclear NMR spectroscopy. AB - The expression of functional antibody fragments in Escherichia coli enables a detailed analysis by NMR spectroscopy. This is demonstrated with the uniform labeling of an Fv-fragment (25 kDa) comprising the antigen binding site of an antibody against 2-phenyloxazolone with 15N and 13C. The antigen-complexed Fv fragment was analysed for a potential assignment by heteronuclear multi dimensional NMR spectroscopy. For almost all backbone amides 15N/1H crosspeaks and for 80% of them TOCSY crosspeaks were observed. In a 13C-edited-HCCH-2D experiment 17 out of 18 threonine spin-systems were identified. Thus detailed assignments are possible, but some amino acid specific labeling in addition to uniform labeling will be required for complete assignments of Fv-fragments. PMID- 1879530 TI - Low-density lipoproteins interact with liposome-binding sites on the cell surface. AB - Under physiological conditions significant amounts of low-density lipoprotein LDL particles ar taken up by cells independently of specific high-affinity LDL receptors (apo-B receptors). Previously it was established that some cells contain surface sites capable of binding liposomes. We proposed that liposome binding sites could contribute to LDL interaction with the cell surface via phospholipid molecules of LDL particles. To check this hypothesis we studied the competitive interaction of human LDL and DPPC liposomes with mouse embryo fibroblasts depleted of apo-B receptors by preliminary incubation with LDL. We have found that after removal of the liposome-binding sites from cell lamellae these areas of the cell surface lose their ability to bind LDL. PMID- 1879531 TI - Daily amylin replacement reverses hepatic glycogen depletion in insulin-treated streptozotocin diabetic rats. AB - In streptozotocin-diabetic rats treated with insulin replacement, liver glycogen is some 35% depleted. Five consecutive daily subcutaneous injections with amylin dose-dependently restored liver glycogen to normal levels. Significant increases over insulin-only therapy occurred with amylin doses of 10, 30 and 100 micrograms/day, representing amylin: insulin ratios of 0.22, 0.75 and 2.79. PMID- 1879532 TI - Reversible expression of sm alpha-actin protein and sm alpha-actin mRNA in cloned cerebral endothelial cells. AB - The expression of smooth muscle (sm) alpha-actin was studied in cloned capillary cerebral endothelial cells of two phenotypes. Type I cells were cultured in medium containing 10% FCS, heparin and ECGS (or alpha-ECGF) and stained positive for a specific endothelial cell marker (Bandeiraea simplicifolia). Depletion of heparin and ECGS resulted in a smooth muscle-like appearance after 2-3 days. Cells of this phenotype, (type II) stained positive for the endothelial cell marker and for sm alpha-actin. In contrast to type I cells, type II cells expressed sm alpha-actin protein and mRNA as evidenced by Immunoblots and Northern blots. This phenotypic switch was shown to be reversible and so was the expression of sm alpha-actin. PMID- 1879533 TI - Penicillin acylase-catalyzed protection and deprotection of amino groups as a promising approach in enzymatic peptide synthesis. AB - Penicillin acylase from E. coli is able to catalyze both the introduction and the removal of the phenylacetyl group. We have established that phenylacetyl derivatives of amino acids and peptides can be used in protease-catalyzed peptide synthesis. Here the synthesis of leucine-enkephalin using enzymes for N-terminal amino group protection, peptide bond formation and deprotection is described. PMID- 1879534 TI - Complete down-regulation of low-density lipoprotein receptor activity in human liver parenchymal cells by beta-very-low-density lipoprotein. AB - The effect of LDL and beta-VLDL on the expression of the LDL receptor is studied in cultured human parenchymal cells. The high affinity binding of [125I]LDL to cultured human parenchymal cells was down regulated to 37.3 +/- 2.9% and 24.0 +/- 2.6% of the control value, after preincubation with LDL or beta-VLDL for 22 h, respectively. When LDL receptor synthesis was blocked at 22 h a residual receptor activity of 29% is noticed, indicating a half-life of LDL receptors in human parenchymal cells of 12 h. It is concluded that LDL receptor expression on human liver parenchymal cells is subject to complete down-regulation by beta-VLDL, which may be held responsible for the cholesterol-rich diet induced down regulation of LDL receptors, in vivo. PMID- 1879535 TI - Cerebellar granule cells in culture exhibit a ganglioside-sialidase presumably linked to the plasma membrane. AB - Cerebellar granule cells differentiated in culture were incubated with ganglioside [3H-Sph]GD1a in order to have it inserted into the plasma membrane, internalized by endocytosis, and metabolized. The metabolites formed included GM1, product of GD1a desialosylation. No GM1 or other metabolites were present in the incubation medium, whereas with the lysosomal apparatus blocked by chloroquine, or GD1a endocytosis prevented at 4 degrees C, the only metabolite formed was GM1. These results suggest that GD1a desialosylation did not occur either extracellularly or intracellularly but likely, at the membrane level. Similar results were obtained with [3H-Gal]GD1b, whereas no degradation of [3H NeuAc]GM1 took place in the presence of chloroquine or at 4 degrees C. In conclusion, cerebellar granule cells express in vivo a sialidase, presumably located on the cell surface, that affects GD1a and GD1b but not GM1. PMID- 1879536 TI - Pericentral expression pattern of glucokinase mRNA in the rat liver lobulus. AB - The spatial distribution of glucokinase mRNA (GK mRNA) in rat liver was studied by in situ hybridization under normal and inducing conditions. GK mRNA was first detectable in the liver parenchyma of neonatal rats of 1.5 days. The density of grains decreases in a central-portal direction. This pattern remains essentially unchanged up to 15 days, after which the adult type of distribution gradually starts to develop, i.e. low density of grains indicating low levels of GK mRNA, in which no gradient of expression could be visualized. Within 2 h after an oral glucose load to starved animals, the GK mRNA expression pattern changed from hardly detectable to a clear gradient with the highest grain density around the terminal central venules. Within 6 h relatively high levels of grains, almost homogeneously distributed across the liver lobule, were observed. Glucocorticosteroid treatment also induced GK mRNA in the pericentral area. It is concluded that the observed induction pattern qualifies GK mRNA as a pericentral mRNA suggesting that the pericentral expression pattern of the protein is primarily regulated at the pretranslational level. PMID- 1879537 TI - Molecular cloning of the ecotin gene in Escherichia coli. AB - The nucleotide sequence of a 876 bp region in E. coli chromosome that encodes Ecotin was determined. The proposed coding sequence for Ecotin is 486 nucleotides long, which would encode a protein consisting of 162 amino acids with a calculated molecular weight of 18,192 Da. The deduced primary sequence of Ecotin includes a 20-residue signal sequence, cleavage of which would give rise to a mature protein with a molecular weight of 16,099 Da. Ecotin does not contain any consensus reactive site sequences of known serine protease inhibitor families, suggesting that Ecotin is a novel inhibitor. PMID- 1879538 TI - Comparative analysis of mitochondrial and amyloplast adenylate translocators. AB - Structurally intact and metabolically competent mitochondria isolated from liquid culture cells of sycamore (Acer pseudoplatanus L.) were shown to incorporate ADPglucose. Employing the double silicone oil layer filtering centrifugation method, we examined the kinetic properties of the uptake of various adenylates as well as the inhibitory effects exerted by carboxyatractyloside, atractyloside and bongkrekic acid, known specific inhibitors of the mitochondrial adenylate translocator. Immunoblot patterns of peptides derived from the partial proteolytic digestion of the mitochondrial and plastid adenylate translocators were shown to be essentially the same. We conclude that the molecular entities engaged in the adenylate transport system operating in two different organelles, mitochondria and amyloplasts, are very similar. PMID- 1879539 TI - Changes in mitochondrial and microsomal rat liver coenzyme Q9 and Q10 content induced by dietary fat and endogenous lipid peroxidation. AB - The influence of different kinds of dietary fat (8%) and of endogenous lipid peroxidation with regard to coenzyme Q9 (CoQ9) and coenzyme Q10 (CoQ10) concentrations in mitochondria and microsomes from rat liver has been investigated by means of an HPLC technique. Although the different diet fats used did not produce any effect on microsomes, it was possible to show that each experimental diet differently influenced the mitochondrial levels of CoQ9 and CoQ10. The highest mitochondrial CoQ content was found in case of a diet supplemented with corn oil. An endogenous oxidative stress induced by adriamycin was able to produce a sharp decrease in mitochondrial CoQ9 levels in the rats to which corn oil was administered. The results suggest that dietary fat ought to be considered when studies concerning CoQ mitochondrial levels are carried out. PMID- 1879540 TI - Novel structurally distinct family of leucocyte surface glycoproteins including CD9, CD37, CD53 and CD63. AB - Several of the recently described leucocyte surface (glyco)-proteins with significant amino acid sequence similarity (human CD9, CD37, CD53, CD63, TAPA-1, CO-029 and R2 and several homologues of other species) are distinguished by the polypeptide chain apparently four times crossing the membrane. Although the biological role of none of these molecules is known, their structure, associations with other membrane components and the effects of specific monoclonal antibodies suggest that they may constitute a family of ion channels or other transport molecules. PMID- 1879541 TI - The lac repressor and its N-terminal headpiece can bind a mini-operator containing a hairpin loop made of a hexaethylene glycol chain. AB - The binding of the lac repressor and the lac repressor N-terminal headpiece to a mini-operator with a hairpin loop made of a hexaethylene glycol chain was investigated using circular dichroism spectroscopy. The lac repressor's headpiece binds to the modified mini-operator with the same affinity as to a mini-operator of the same sequence without the hexaethylene glycol loop. The conformational effect due to the binding is not affected by the presence of the hexaethylene loop. It is also shown that the entire lac repressor binds to this modified mini operator inducing a conformational change. PMID- 1879542 TI - Melatonin binding proteins identified in the rat brain by affinity labeling. AB - N-Bromoacetyl-2-iodo-5-methoxytryptamine (BIM), a novel derivative of the biologically active melatonin analog, 2-iodomelatonin, was prepared and used to identify melatonin binding proteins in rat brain synaptosomes. Incubation of the synaptosomes with BIM resulted in a time and concentration dependent, irreversible inhibition of 2-[125I]iodomelatonin binding. In parallel, the radioactive form of BIM, N-bromoacetyl-2-[125I]iodo-5-methoxytryptamine ([125I]BIM) became incorporated into the synaptosomes. The incorporation of [125I]BIM was inhibited by BIM, 2-iodomelatonin and melatonin but not by 5 methoxytryptamine or N-acetyl serotonin. [125I]BIM became covalently attached to three polypeptides with apparent molecular weight values of 92, 55 and 45 kDa; the labeling of all three proteins was markedly inhibited by melatonin. These results indicate that the 92, 55 and 45 kDa polypeptides are melatonin binding proteins. PMID- 1879543 TI - Probing the secondary quinone (QB) environment in photosynthetic bacterial reaction centers by light-induced FTIR difference spectroscopy. AB - The photoreduction of the secondary electron acceptor, QB, has been characterized by light-induced Fourier transform infrared difference spectroscopy of Rb. sphaeroides and Rp. viridis reaction centers. The reaction centers were supplemented with ubiquinone (UQ10 or UQ0). The QB- state was generated either by continuous illumination at very low intensity or by single flash in the presence of redox compounds which rapidly reduce the photooxidized primary electron donor P+. This approach yields spectra free from P and P+ contributions making possible the study of the microenvironment of QB and QB-. Assignments are proposed for the C...O vibration of QB- and tentatively for the C = O and C = C vibrations of QB. PMID- 1879544 TI - Supramolecular structure of the recombinant murine small heat shock protein hsp25. AB - The size and shape of the recombinant murine small heat shock protein, hsp25, have been analyzed by hydrodynamic and electron microscopic methods. According to these studies recombinant hsp25 exists in large complexes with a sphere-like shape and diameters of 15-18 nm. The molecular mass of these complexes amounts to about 730 kDa indicating that they are composed of about 32 monomers. PMID- 1879545 TI - The phospholipid analogue hexadecylphosphocholine inhibits phosphatidylcholine biosynthesis in Madin-Darby canine kidney cells. AB - The influence of the phospholipid analogue hexadecylphosphocholine on phosphatidylcholine biosynthesis was investigated in Madin-Darby canine kidney (MDCK) cells. It inhibits the incorporation rate of [methyl-3H]choline into phosphatidylcholine at a concentration of 50 microM by about 50%. The radiolabelled precursor accumulates in the phosphocholine pool indicating that hexadecylphosphocholine inhibits the formation of phosphatidylcholine via the CDP choline pathway at the level of the rate-limiting enzyme. CTP:phosphocholine cytidylyl transferase (EC 2.7.7.15). This was verified by the determination of the activity of the enzyme in vitro. In consequence of its inhibitory effect it could be shown that the treatment of MDGK cells for 24 h with 50 microM hexadecylphosphocholine induces alterations of the phospholipid composition. Whereas in treated cells the relative phosphatidylcholine content was decreased from the control level of 36.0 +/- 0.9% to 29.9 +/- 0.2%; in contrast, the relative content of phosphatidylethanolamine was increased from 19.3 +/- 0.9% to 24.3 +/- 0.9%. PMID- 1879546 TI - The dynamics of the expression of C/EBP mRNA in the adult rat liver lobulus qualifies it as a pericentral mRNA. AB - A hybridocytochemical approach has been applied to establish whether the gene for the C/EBP mRNA might be involved in the topographical regulation of gene expression in adult rat liver. To that end the spatial distribution of the mRNA of C/EBP has been compared to that of the mRNAs of glutamine synthetase (GS), phosphoenolpyruvate carboxykinase (PEPCK) and glucokinase (GK) in normal adult livers, in livers from dexamethasone-treated animals and in livers from starved animals refed with glucose for 4 h. In normal rat liver, in situ hybridization with a probe for C/EBP mRNA revealed a low density of apparently homogeneously distributed grains, indicating low levels of C/EBP mRNA. In contrast, the livers of the experimentally-treated animals revealed a zonal distribution of the mRNA of C/EBP with the highest density of grains around the central venules. The dynamics of the pattern of expression of C/EBP mRNA are virtually identical to that of the GK mRNA. These data qualify C/EBP mRNA as a pericentral mRNA and suggest a role for the C/EBP protein in the topographical regulation of the expression of the GK mRNA. PMID- 1879547 TI - The amino acid sequence of rusticyanin isolated from Thiobacillus ferrooxidans. AB - The amino acid sequence of rusticyanin, a copper protein, purified from the iron oxidizing bacterium Thiobacillus ferrooxidans was determined. Rusticyanin contained 154 amino acid residues in a single polypeptide chain and its molecular weight was calculated to be about 16,400 based on the amino acid sequence. The N terminal sequence up to the 20th residue of the protein apparently resembled those of Methylobacterium extorquens AM1 amicyanin and poplar leaf plastocyanin rather than those of azurin family proteins. In the C-terminal region of the sequence, rusticyanin had one cysteine, one histidine and one methionine which are conserved through many copper proteins. In the middle region of the sequence, rusticyanin was not similar to any other copper protein. The sequence nearby His84 of rusticyanin was similar to those of other copper proteins to some extent. However, Asn which follows His84 and is highly conserved in other copper proteins did not exist in rusticyanin. Therefore, it seemed difficult to conclude on the basis of the results obtained in the present study that His84 in rusticyanin was the fourth ligand to the copper atom. PMID- 1879548 TI - Shaw-like rat brain potassium channel cDNA's with divergent 3' ends. AB - The complete amino acid sequence of a potassium channel protein of rat brain, Kv3.2b, plus a partial sequence of a related channel, Kv3.2c, are deduced from molecular cloning of the respective cDNA's. Kv3.2b and Kv3.2c share extensive amino acid sequence identity with a previously identified channel, RKShIIIA[1], before diverging to unique carboxy termini. Probes specific for Kv3.2b and RKShIIIA detect similarly sized mRNA's on Northern blots. These two proteins are encoded by a single gene based on genomic Southern blotting, and therefore arise by alternative splicing. In vitro transcribed mRNA for Kv3.2b induces the expression of outward K+ currents in Xenopus oocytes under voltage-clamp conditions. PMID- 1879549 TI - Deletion of exon 8 causes glycosylasparaginase deficiency in an African American aspartylglucosaminuria (AGU) patient. AB - We have indentified a GT-to-TT transversion at the splice donor site of intron 8 in the glycosylasparaginase gene from an African American aspartylglucosaminuria (AGU) patient. This mutation causes abnormal splicing of glycosylasparaginase pre mRNA by joining exon 7 to 9 and excluding 134 bp exon 8. The effect of the mutation is compounded by a frame shift that occurs after the deletion site resulting in premature translational termination. The truncated AGU protein was neither catalytically active nor processed into mature alpha and beta subunits. Both this and a previously characterized Finnish AGU mutation appear to affect folding of the single-chain precursor of glycosylasparaginase and thereby prevent transport of the enzyme to lysosomes. PMID- 1879550 TI - Occurrence of bifurcated three-center hydrogen bonds in proteins. AB - Analysis of 13 high-resolution protein X-ray crystal structures shows that 1204 (24%) of all the 4974 hydrogen bonds are of the bifurcated three-center type with the donor X-H opposing two acceptors A1, A2. They occur systematically in alpha helices where 90% of the hydrogen bonds are of this type; the major component is (n + 4)N-H ... O = C(n) as expected for a 3.6(13) alpha-helix, and the minor component is (n + 4)N-H ... O = C(n + 1), as observed in 3(10) helices; distortions at the C-termini of alpha-helices are stabilized by three-center bonds. In beta-sheets 40% of the hydrogen bonds are three-centered. The frequent occurrence of three-center hydrogen bonds suggests that they should not be neglected in protein structural studies. PMID- 1879551 TI - Internal deletions of amino acids 29-42 of human interleukin-6 (IL-6) differentially affect bioactivity and folding. AB - Internal deletions of the human interleukin-6 (IL-6) cDNA have been generated in the region encoding residues 29 to 42. Mutant proteins were produced by in vitro transcription-translation or in Escherichia coli and tested for their biological activity using the hybridoma growth factor (HGF) assay or a transcriptional activation assay on human hepatoma cells. The folding of the mutants was also checked by immunoprecipitation with conformation-specific monoclonal antibodies. The results show that only residues 29 to 34 are crucial for IL-6 activity and that the first two amino acids are probably involved in the definition of the IL 6 active site. PMID- 1879552 TI - Thyroid hormone increases glyceraldehyde 3-phosphate dehydrogenase gene expression in rat liver. AB - Livers from hypophysectomized rats had low levels of glyceraldehyde 3-phosphate dehydrogenase mRNA. Administration of L-triiodothyronine increased these levels over 20-fold. The peak response was seen 72 h after hormone administration. A half-maximal response was obtained with 5 micrograms of T3 per 100 g of body weight. Thus the expression of hepatic glyceraldehyde 3-phosphate dehydrogenase appears to be regulated by thyroid hormone. PMID- 1879553 TI - Pentasialogangliosides of human brain. AB - A pentasialoganglioside fraction of the ganglio series of glycosphingolipids has been isolated from human cerebellar cortex with a yield of 8.8 nmol NeuAc per g fresh tissue. The structural analysis showed that the material was a mixture of GP1b and GP1c gangliosides. PMID- 1879554 TI - Inhibition of 5S RNA transcription in vitro by nucleosome cores with low or high levels of histone acetylation. AB - Nucleosomes exert strong inhibitory effects on gene transcription in vitro and in vivo. Since most DNA is packaged in nucleosomes, there must exist mechanisms to alleviate this inhibition during gene activation. Nucleosomes could be destabilized by histone acetylation which is strongly correlated with gene expression. We have compared the effects of nucleosomes cores with low or high levels of histone acetylation on 5S RNA transcription with Xenopus nuclear extracts in vitro. Little or no difference was observed over a range of 1 to 15 nucleosome cores per plasmid template. This result suggests that nucleosomal DNA is not more accessible to transcription factors and to the transcription machinery in acetylated nucleosomes. PMID- 1879555 TI - 6-Hydroxymellein synthetase as a multifunctional enzyme complex in elicitor treated carrot root extract. AB - Synthetic activity of a polyketide compound 6-hydroxymellein was induced in elicitor-treated carrot root tissues. The activity was significantly inhibited by an antiserum raised against the acyl carrier protein (ACP) of fatty acid synthetase, suggesting that the enzyme(s) for 6-hydroxymellein synthesis require(s) a functional unit similar to ACP. However, the synthetic activity was not stimulated by the addition of ACP purified from Escherichia coli and was not lost even after fractionation by gel-filtration chromatography. The active fraction obtained by gel-filtration (136 kDa) was subjected to immunoblot analysis, and a 128 kDa polypeptide in the fraction was found to cross-react with anti-ACP serum. These observations suggest that the biosynthesis of 6 hydroxymellein in carrot cells is catalyzed by an enzyme consisting of a single peptide chain. PMID- 1879556 TI - Differences between embryonic and adult Torpedo acetylcholine receptor gamma subunit. AB - Antibodies to a synthetic peptide corresponding to residues 346-359 of the Torpedo acetylcholine receptor (AChR) gamma subunit, were employed to compare the adult and embryonic receptor. This peptide contains a consensus phosphorylation site for cAMP-dependent protein kinase (PKA). The anti-peptide antibodies discriminated between adult and embryonic AChRs, and reacted preferentially with the adult gamma form. These observed immunological differences did not seem to stem from different phosphorylation states. Our results suggest that the embryonic Torpedo AChR may have a gamma-like subunit that differs from the known adult form of this subunit, at least in the specific region that contains the phosphorylation site for PKA. PMID- 1879557 TI - Induction of heat-shock proteins by glutamine. The 'feeding effect'. AB - Subconfluent, log-phase Chinese hamster ovary cells induced the major heat-shock proteins (hsp) when cells were refed, 40 hours after seeding. This method of inducing heat-shock proteins was also obtained by refeeding with fresh serum-free media, but not with media with a long shelf life or with media prepared without glutamine. It was observed that addition of glutamine alone to cultures at 40 hours post-seeding induced heat-shock proteins. Addition of ammonium chloride, however, had no discernible effect on heat-shock protein synthesis. Northern blot analysis indicated that this phenomenon reflected an increase in the levels of message for the constitutive/inducible member of the hsp 70 family, but not the non-constitutive member. To determine the effect of this induction on heat sensitivity, unfed and 'heat-shock-induced' refed cultures were heated at 45 degrees C. No significant difference in cell survival was observed. Therefore glutamine is the necessary ingredient required for the induction of heat-shock proteins and this method of inducing heat-shock proteins does not alter heat sensitivity. PMID- 1879558 TI - Significant correlations between atmospheric spectra according to Baumer and the in vitro incorporation of [3H]thymidine into the nuclear DNA of C6-glioma cells. AB - Significant correlations between certain spectra of atmospherics (spherics) according to Baumer (a.t.B), i.e. naturally occurring electro-magnetic impulses in the range of 4-50 kHz, and several diseases or biological parameters have been published earlier. Now we show that there exists a highly significant negative correlation (r = -0.61, P greater than 0.004) between the occurrence of 28 kHz impulses (a.t.B.) and the in vitro incorporation of thymidine into the nuclear DNA of C6-glioma cells. The positive correlation with the 10 kHz impulses (a.t.B) (r = 0.39), however, is statistically not significant (P greater than 0.055). PMID- 1879559 TI - Studies on the distribution of cellular myosin with antibodies to isoform specific synthetic peptides. PMID- 1879560 TI - Enhanced cellular uptake of biotinylated antisense oligonucleotide or peptide mediated by avidin, a cationic protein. AB - The cellular uptake of a model antisense oligonucleotide complementary to 21 bases of the bovine GLUT-1 glucose transporter mRNA and a model vasopressin peptide that were biotinylated, was markedly stimulated by the presence of avidin, a cationic protein. Conversely, the bacteria homologue of avidin, streptavidin, which is a slightly acidic protein, did not facilitate cellular uptake. The avidin-mediated uptake of biotinylated derivatives was competitively inhibited by another cationic protein, protamine, with a Ki of 5 micrograms/ml; was saturable, temperature- and time-dependent; and was associated with endocytosis. The use of the avidin-biotin system provides a new approach to increasing the cellular uptake of antisense oligonucleotides or peptides. PMID- 1879561 TI - Lipoprotein lipases and vitellogenins in relation to the known three-dimensional structure of pancreatic lipase. AB - A 106-residue region of high similarity between lipoprotein/pancreatic/hepatic lipases and Drosophila vitellogenins encompasses four beta-strands with all residues but one strictly conserved or conservatively replaced between the structures, and enclosing the putative active site Ser-152. The properties suggest a common folding pattern but the region probably does not function as an 'interface recognition site' in the lipases, although it might well bind fatty acid esters of ecdysteroids or single lipid molecules in the vitellogenins. C terminally of this 106-residue region, a surface loop ('flap') covers the active site. No residue within this loop is conserved through all lipases, but adjacent segments exhibit 60-70% residue identity. Hepatic and lipoprotein lipases probably hydrolyze both soluble and emulsified substrates at the same site. They lack residues corresponding to a second active site postulated in pancreatic lipase to account for hydrolysis of soluble substrates. In addition, due to structural differences the flap could prevent entry of soluble substrate molecules into the active site of pancreatic lipase. PMID- 1879562 TI - Purification and characterization of the alpha-tocopherol transfer protein from rat liver. AB - alpha-Tocopherol transfer protein was purified from the 10,000 x g supernatant of rat liver. Two isoforms of the transfer protein exist, of which the isoelectric points are 5.0 and 5.1 as determined by chromatofocusing. These two isoforms have the same molecular weight; both showed molecular weight of approx. 30,500 on SDS polyacrylamide gel electrophoresis. They cannot be distinguished from each other by amino acid composition or substrate specificity. PMID- 1879563 TI - Suppression by staurosporine of Ca(2+)-mobilization triggered by ligation of antigen-specific receptors on t and B lymphocytes. An essential role of protein tyrosine kinase in the signal transduction. AB - It is known that the receptor for platelet-derived growth factor (PDGF) activates phospholipase C (PLC) by phosphorylating the gamma 1 isoform of PLC with the receptor protein-tyrosine kinase (PTK), whereas a guanine nucleotide-binding protein participates as a transducer in the PLC activation through the receptors for vasopressin, bombesin and prostaglandin F2 alpha (PGF2 alpha). We have shown in a rat fibroblast line that staurosporine is a potent PTK inhibitor capable of clearly discriminating the two types of receptor-stimulated Ca2+ mobilization and, by inference, PLC activations the response triggered by PDGF was completely inhibited, whereas the responses triggered by vasopressin, bombesin and PGF2 alpha were not affected at all. The Ca2+ mobilization in human T and B cell lines induced by anti-CD3 and anti-immunoglobulins (Ig) was completely suppressed by staurosporine. The results indicate that the PTK activity plays an essential role in the PLC activation through the T cell receptor/CD3 complex and through membrane Ig. PMID- 1879564 TI - Activation of the PKC-isotypes alpha, beta 1, gamma, delta and epsilon by phorbol esters of different biological activities. AB - Phorbol esters, tetradecanoylphorbolacetate, sapintoxin-A, 12-deoxyphorbol phenylacetate, 12-deoxyphorbol-phenylacetate-20-acetate, thymeleatoxin and resiniferatoxin were investigated for their abilities to activate the PKC isotypes alpha, beta 1, gamma, delta and epsilon. PKC-isotypes were grouped into two classes on the basis of Ca2+ requirements for activation by phorbol esters; alpha, beta 1, and gamma being Ca(2+)-dependent forms and delta and epsilon being Ca(2+)-independent. PKC-isotype selective activation by phorbol esters was observed in that SAPA failed to activate PKC-delta up to a concentration of 1000 ng.ml-1 and DOPPA only activated PKC-beta 1 over the same range of concentrations. PMID- 1879565 TI - Heterogeneity in the Xenopus ribosomal transcription factor xUBF has a molecular basis distinct from that in mammals. AB - The Xenopus polymerase I transcription factor xUBF is an HMG-box protein which has been purified as two polypeptides of approximately 82 and 85 kDa. Recently a cDNA sequence predicted an xUBF protein (xUBF1) of 677 amino acids (79 kDa) containing five tandem HMG-boxes. Here a second and distinct xUBF cDNA has been isolated and characterised. This cDNA codes an xUBF protein (xUBF2) of 701 amino acids (82 kDa), having 93% homology with xUBF1 but containing an insertion of 22 amino acids between HMG-boxes 3 and 4. In vitro translation of synthetic mRNAs derived from the xUBF1 and 2 cDNAs was used to show that the electrophoretic mobility of the gene products accounted for the major xUBF molecular weight heterogeneity noted in vivo. It is also shown that the Xenopus laevis genome contains 3 or 4 distinct loci which hybridise with xUBF coding sequences, leaving open the possibility of yet further unrecognised heterogeneity in xUBF. PMID- 1879566 TI - Expression and functional assembly into bacterial ribosomes of a nuclear-encoded chloroplast ribosomal protein with a long NH2-terminal extension. AB - Chloroplast ribosomal protein L13 is encoded in the plant nucleus and is considerably larger than its eubacterial homologue by having NH2- and COOH terminal extensions with no homology to any known sequences (Phua et al., J Biol. Chem. 264, 1968-1971, 1989). We made two gene constructs of L13 cDNA using the polymerase chain reaction (PCR) and expressed them in Escherichia coli. Analysis of the ribosomes and polysomes from these cells, using an antiserum specific to chloroplast L13, shows that the expressed proteins are incorporated, in the presence of the homologous E. coli L13, into functional ribosomes which participate in protein synthesis (i.e. polysomes). Evidence is obtained that the large NH2-terminal extension probably lies on the surface of these 'mosaic ribosomes.' This first report of the assembly into E. coli ribosomes of nuclear coded chloroplast ribosomal protein with terminal extensions thus suggest an extraordinary conservation in the function of eubacterial type ribosomal proteins, despite the many changes in protein structure during their evolution inside a eukaryotic system. PMID- 1879567 TI - Immunochemical identification of branched-chain 2-oxo acid dehydrogenase kinase. AB - Branched-chain 2-oxo acid dehydrogenase kinase was characterized using anti kinase polyclonal antibodies. The antibodies were purified from rabbit antiserum by an epitope selection method. The antibodies bound only to a 44 kDa polypeptide in the dehydrogenase-kinase complex and inhibited the kinase activity, substantiating that the 44 kDa polypeptide is the catalytic subunit of the kinase. The purified liver dehydrogenase-kinase complex, but not either the purified heart complex or the partially purified liver complex, contained 2 additional polypeptides of lower molecular weight which also reacted with the anti-kinase antibodies, suggesting that the liver kinase is subject to proteolytic degradation during purification. PMID- 1879568 TI - General principles of healing pertinent to the periodontal problem. AB - The healing process involves a series of coordinated procedures initiated by injury and directed toward restoring structural and functional integrity of the disrupted tissues. Wound healing begins immediately after tissue injury occurs and requires close control of degenerative and regenerative processes, which involve numerous cell types and complex interactions between multiple biochemical cascades. PMID- 1879569 TI - Reconstructive periodontics. PMID- 1879570 TI - Biology of tooth-cell adhesion. AB - Guided tissue regeneration appears to be a very promising approach to achieve the regeneration of periodontal tissue. Several important questions remain, such as the role of bone-derived cells, the length of time the physical barriers should be left in place, and whether anatomic factors, such as the morphology of periodontal defects, affect the outcome of the procedure. Potential applications of this procedure include combining bone grafting techniques with guided tissue regeneration, the use of growth factors to enhance periodontal tissue regeneration, and the repairing of bone defects around endosseous implants. Future research in this area is needed to address some of the present concerns and to improve the predictability of this procedure. PMID- 1879571 TI - Healing and repair of osseous defects. AB - This article has discussed most of the modalities currently in use for the filling of bony defects. No one modality or combination of methods or materials has yet surfaced as the definitive means of treatment for filling these defects. PMID- 1879572 TI - Principles and techniques of guided tissue regeneration. AB - Guided tissue regeneration is an accepted technique to promote new attachment in periodontal therapy. It is supported by sound basic research indicating that the definitive factor in the obtainment of regeneration is the source from which the cells repopulating the exposed root surface originate. These studies have indicated that cells proliferating from the periodontal ligament have the greatest potential for achieving new attachment. The use of barriers during periodontal surgery permits the possibility of periodontal ligament proliferation toward the exposed root at the same time that epithelial and gingival connective tissue proliferation is blocked. Studies in which Gore-Tex periodontal material has been used as a barrier have shown positive results in animal and clinical studies. Histologically, the formation of new cementum, bone, and periodontal ligament has been demonstrated. Clinically, beneficial results have been documented in the treatment of intrabony defects with three-wall, two- to three wall, or funnel-shaped topography. Also, Class II furcations with or without a vertical component have been treated successfully by guided tissue regeneration. PMID- 1879573 TI - Coronally displaced flaps in reconstructive periodontal therapy. AB - This article reviews the approach taken by the Loma Linda University Group in treating molars with Class II and Class III furcation lesions. The surgical technique used is detailed for Class II furcations. The modification of the technique for lingual furcation of lower molars and the postsurgical behavior of a crown-attached flap are also discussed. PMID- 1879574 TI - Freeze-dried bone allografts in periodontal reconstructive surgery. AB - The objectives of a bone graft are reversal of the disease process, probing depth reduction, clinical attachment gain, clinical repair of lost bone, and histologic reconstruction of the attachment apparatus consisting of new bone, cementum, and periodontal ligament in an area previously exposed to bacterial plaque. The article discusses the current clinical and histologic state-of-the-art with regard to undermineralized freeze-dried bone allograft and demineralized freeze dried bone allograft. Specific conclusions about the use of freeze-dried bone allograft are listed. PMID- 1879575 TI - Alloplastic materials in reconstructive periodontal surgery. AB - Alloplastic implants, especially those made with calcium phosphate ceramics, are being increasingly used in reconstructive periodontal surgery. Despite attractive generic features such as good biocompatibility, these ceramic implants differ significantly from each other in terms of biologic profile. Variations in source material used, manufacturing process, and physical and chemical properties determine the clinical utility of these implants. Porous hydroxyapatites currently are favored, especially those with natural morphologic characteristics. These ceramic implants appear to serve as biocompatible fillers that accelerate bone healing when used for the right clinical indications. It is anticipated that alloplastic implants eventually will form a part of the periodontist's armamentarium. PMID- 1879576 TI - Surgical techniques for reconstructive periodontics. AB - The careful selection of the "graftable" case and the attention to details in the surgical technique increase the predictability of results in reconstructive periodontal therapy. When choosing a surgical technique for reconstructive periodontal therapy, the clinician must carefully consider the following: 1. Flap and incision design to best avoid exposure and contamination of the graft material. 2. Thorough debridement of the osseous lesion for intimate graft contact with the osseous walls. 3. Careful and complete planing of the root surface to the apical end of the vertical osseous lesion. 4. Suturing technique to prevent contamination of the graft material and to obtain a seal between the flap and the root surface. 5. Careful hygiene methods postsurgically to prevent infections during the healing process. PMID- 1879577 TI - Current status of periodontal therapy for furcation involvements. AB - The treatment of furcation involvements is difficult because of the anatomic problems that interfere with the clinician's accessibility in treating the area and the patient's ability in maintaining adequate plaque control afterwards. The goal of traditional methods of treatment is to arrest the progression of bone loss; the rate of success with these methods has been poor, except for Grade I involvements. Advances in the last decade have resulted in the development of treatment techniques that attempt to reconstruct the lost periodontal structures. These techniques have greatly improved the prognosis of Grade II furcation involvement. The recommended technique combines the principles of guided tissue regeneration using polytetrafluoroethylene membranes with grafting with porous hydroxyapatite. The use of decalcified freeze-dried bone instead of hydroxyapatite also may be a successful method. Grade III and IV furcation involvements still have a poor long-term prognosis because predictable reconstructive techniques for their treatment have not been demonstrated. When possible, a root resection approach may be advisable. PMID- 1879578 TI - Supportive periodontal therapy after reconstructive periodontal surgery. AB - Clinical practice and research have established the value of supportive periodontal treatment after reconstructive periodontal surgery. The clinical procedures and the rationale for developing individualized treatments are discussed in general and for specific types of reconstructive procedures. The application of adjunctive diagnostics and chemotherapeutic agents to supplement traditional methods is described. PMID- 1879579 TI - Bone growth around dental implants. AB - For the complete understanding of stimulation of bone growth around dental implants, a thorough knowledge is necessary regarding the reaction of bone to trauma and to a variety of implant materials. The atraumatic preparation of the bony implant bed serves to create the most favorable situation for the formation of bone around any implant material. Some implant materials are more likely to result in soft tissue encapsulation despite the most careful handling of bone; others result in different amounts of implant-bone contact zones. From the character and the amount of bone formation around different implants, it can be concluded whether the used materials are biocompatible. Titanium-surfaced implants may not demonstrate the biocompatibility that is seen with hydroxyapatite-coated implants. However, the results seen with hydroxyapatite coated implants have to be viewed critically because the biointegrity of these coatings has not been demonstrated until now. On the other hand, titanium surfaced implants have success rates for as long as 25 years and enable the implantologist to rely on a well-accepted implant material. The use of guided tissue regeneration and the sinus augmentation technique appear to enable the implantologist to stimulate bone formation around dental implants. These techniques may extend the limits for the successful placement of dental implants into bone-deficient sites. PMID- 1879580 TI - A new syndrome is born. PMID- 1879581 TI - Borrelia burgdorferi and different types of morphea. AB - Thirty patients with different clinical manifestations of morphea (circumscribed scleroderma) were investigated for serum antibodies against Borrelia burgdorferi determined by ELISA and Western blot analysis. Forty-six percent of the patients were seropositive. Western blots confirmed the ELISA results in 10 of 25 patients (40%), showing a reactivity pattern which can be seen in the course of Lyme borreliosis. In some cases the outcome after antibiotic treatment suggests a direct correlation between the further development of skin lesions and Borrelia infection. Because of these findings we suggest some morphea types to be possibly due to a B. burgdorferi infection. PMID- 1879582 TI - Porphyria cutanea tarda associated with human immunodeficiency virus infection. A study of four cases and review of the literature. AB - We report the cases of 4 male subjects, 29, 32, 41 and 44 years old, presenting isolated seropositivities for the human immunodeficiency virus (HIV), or full blown acquired immunodeficiency syndrome, associated with a typical porphyria cutanea tarda (PCT). The 4 patients are in the usual risk groups for HIV infection. Viral hepatitis was observed in 3 of the 4 cases. Over the past 3 years, 15 cases associating HIV infection and PCT have been reported; almost all had the usual risk factors for HIV infection and hepatopathy. We speculate that HIV infection may have favored the occurrence of early PCT in these cases by altering the metabolism of the porphyrins, either directly or by means of the associated hepatopathy. PMID- 1879583 TI - Complement allotypes in Japanese patients with pemphigus and bullous pemphigoid. AB - The allotypes of C6, C7, factor B (BF) and factor I (IF) of the human complement system were studied in 11 Japanese patients with pemphigus (5 with pemphigus vulgaris and 6 with pemphigus foliaceus) and 17 with bullous pemphigoid (BP) to investigate the genetic background of these diseases. The allotypes were detected by using isoelectric focusing and immunoblotting. The frequency for IF*A allele in the pemphigus patients was significantly higher (p = 0.009) than that in healthy controls (n = 60). A significant association of IF A allotype with pemphigus was also observed (p = 0.027), with a relative risk of 6.3. There was no association between the C6, C7, BF or IF allotypes and BP. These data suggest that IF A allotype may be an etiological genetic factor in the development of pemphigus. PMID- 1879584 TI - Study of the primary crest 'pavement' structure in healthy skin. AB - The primary crest surface of the healthy skin may have a smooth appearance or form a 'pavement'-like picture because of the presence of circular or polygonal subunits. In this study, the primary crest pavement structure was examined in different sites of healthy skin. The pavement structure was found in 70-100% of the adjacent areas of the palms and soles, and also on the skin of the elbows and knees. This pavement formation is absent on the skin surface of other areas or may be found in a small percentage of 5-20%. It is possible that the pavement structure could represent modified dermatoglyphics in the hairy skin. PMID- 1879585 TI - Pili torti and onychodysplasia. Report of a previously undescribed hidrotic ectodermal dysplasia. AB - Ectodermal dysplasias are a large and heterogeneous groups of clinically and genetically distinct syndromes. We studied a family suffering from dystrophies of the distal part of the nails and trichodysplasia. Scalp, beard, pubic and axillary hair were broken off leaving a stubble 1-10 mm in length. Eyebrows, eyelashes and body hair were completely absent. Serum levels of copper and plasma levels of amino acids were within the normal range. Inheritance was autosomal recessive. Previous reports of ectodermal dysplasias and other complex syndromes with pili torti are reviewed. PMID- 1879586 TI - Unusual form of melanocytic nevus associated with Turner's syndrome. AB - An 11-year-old girl with Turner's syndrome developed a combined nevus on the back. The examination of the excised specimen revealed the combination of common compound nevus and a component of Spitz's nevus. Numerous melanocytic nevi are a feature of Turner's syndrome, but this appears to be the first case of a combined nevus with Spitz's component. PMID- 1879587 TI - Verrucous carcinoma of a leg amputation stump. AB - Verrucous carcinoma of the skin is a rare cancer which tends to appear on the soles of the feet, although it can appear elsewhere on the cutaneous surface. It has not, to our knowledge, been previously reported on a leg amputation stump. PMID- 1879588 TI - Persistent light reaction associated with photoallergic contact dermatitis to musk ambrette and allergic contact dermatitis to fragrance mix. AB - A 57-year-old man suffering from persistent light reaction with photocontact allergy to musk ambrette and contact allergy to fragrance mix was evaluated. A lowered minimal erythema dose to UV-B (MED-UV-B) was seen. Reactions to long-wave UV-A and visible radiation were normal. A skin biopsy from one MED-UV-B, taken 24 h after irradiation, showed acute spongiotic dermatitis. PMID- 1879589 TI - Green hair caused by copper present in cosmetic plant extracts. PMID- 1879590 TI - Darier's disease and corneal opacity. PMID- 1879591 TI - Breech presentation and cesarean section. PMID- 1879592 TI - Safety of term vaginal breech delivery. AB - Of 247 women who were pregnant of one healthy child in breech presentation at term, 13 (5.3%) were delivered by a primary cesarean section. The other 234 (94.7%) were allowed to attempt vaginal birth. In these women, the only factor to determine the possibility of a vaginal delivery was normal progression of labor during the first stage, without secondary arrest or signs of fetal distress. 109 Women (44.1%) were delivered spontaneously according to Bracht, 87 (35.2%) had an assisted breech delivery, and 38 (15.4%) underwent a secondary cesarean section. There were two perinatal deaths (0.8%). One of them was directly related to the trial of labor. Two children with a birth trauma had an uneventful recovery. The 1 min Apgar score in all breech delivery groups was more often lower than in a control group of children, who were born spontaneously at term in vertex presentation. However, the 5 min Apgar score and the mean umbilical artery pH were within normal limits in all groups. The secondary cesarean section rate was inversely related to vaginal parity of the mother, and directly related to the newborns' birth weight. There was no relation between the secondary cesarean section rate and the type of breech presentation. It is concluded, that a trial of labor in carefully selected patients with a child in breech presentation at term is a safe procedure, that can be successfully completed in almost 80% of cases. In retrospect, low vaginal parity and high birth weight of the newborn have a negative influence on normal progression of labor. PMID- 1879593 TI - Placental morphology in relation to umbilical artery blood velocity waveforms. AB - The association between umbilical artery flow velocity waveforms, placental morphology and arterial vascular pattern was investigated in 30 pregnant women at risk for intra-uterine growth retardation. The blood velocity waveform was assessed in the umbilical arteries with pulsed Doppler ultrasound. Placentas from fetuses with an end-diastolic zero flow were small and thick with an extrachorial configuration, marginal cord insertion, magistral or mixed allantochorial vessel pattern and few cotyledons. The incidence and the extension of gross lesions were slightly increased in these placentas compared to placentas from fetuses with a normal S/D ratio (peak systolic velocity/minimum diastolic velocity). Placentas from fetuses with an increased S/D ratio (greater than +2SD) were large and thin with a high maximum diameter/maximum thickness ratio. Heavily smoking mothers were overrepresented in the group, with an increased S/D ratio and corresponding SGA infants. End-diastolic zero flow in the umbilical artery was strongly correlated with placental developmental abnormalities. PMID- 1879594 TI - Assessment of tobacco-exposure during pregnancy; behavioural and biochemical changes. AB - Smoking-behavior during pregnancy and the reliability of an interview were prospectively investigated. The tobacco-exposure was assessed a) by an intake interview b) by a smoking diary and c) by maternal thiocyanate and carboxy hemoglobin concentrations. Of the 115 nulliparous women, 66 smoked (57.4%). Seventeen women (25.8%) quit and 39 women (59.1%) reduced smoking. Directly after intake, in the first week of the diary, significantly more cigarettes were smoked than stated during the intake interview. According to the diaries, the number of cigarettes increased during the first half of pregnancy. In the 24th week significantly more cigarettes were smoked than in the first week after intake. Also a significant increase of thiocyanate between the measurements at intake and in the 24th of amenorrhea was found. The maternal carboxy-hemoglobin levels did not significantly change during pregnancy. Investigators should be aware of changes in smoking behavior during pregnancy and the potential bias of self reported smoking behavior at the beginning of pregnancy. The tobacco-exposure should be assessed (anamnestic or biochemical) several times during pregnancy, anyway it should include the second half of pregnancy. PMID- 1879595 TI - The use of micronized progesterone in the treatment of menace of preterm delivery. AB - The results of a study concerning the treatment of acute menace of preterm labor are given: beta-mimetics were administered intravenously in all cases (44) and micronized progesterone or placebo was administered orally after classical double blind randomization (22 cases in each group). The mean index of pregnancy prolongation was the same in both groups. However the mean duration of the intravenous perfusion and the mean quantity of beta-mimetics administered intravenously were significantly reduced in the progesterone group (P less than 0.01). The mean duration of hospital stay was also significantly reduced (P less than 0.05). Cost and risks are finally significantly lessened. PMID- 1879596 TI - Sex ratio of spontaneously aborted fetuses and delivered neonates in second trimester. AB - The author investigated in patient material from 12 years 251 cases involving spontaneous abortion and delivery in the second trimester. The material included 28 sets of twins and one set of triplets, thus the total number of fetuses and neonates was 281. The sex ratio was 136.1, higher than that documented natural sex ratio in the second trimester or at term. The ratio approaches that experienced in cases of perinatal death. PMID- 1879597 TI - Increased plasma levels of the novel vasoconstrictor peptide endothelin in severe pre-eclampsia. AB - Plasma endothelin levels were studied in 29 pregnancies. Levels were found to be increased in 9 pregnancies complicated by pregnancy-induced hypertensive disease and/or pre-eclampsia as compared to levels in 14 normotensive pregnancies with gestational age varying between 24-40 weeks with normal Doppler flow velocity waveforms of the uterine arcuate arteries, and 6 normotensive pregnancies with abnormal Doppler flow velocity waveforms at 24 weeks' gestation. Two patients with severe pre-eclampsia showed a rise in plasma endothelin levels, suggesting a correlation between plasma endothelin levels and the disease process. Endothelin is produced by endothelial cells of blood vessels; it is the most potent vasoconstrictor known to date. For this reason it has been suggested that endothelin might be important in the control of systemic blood pressure and local blood flow, both disturbed in pre-eclampsia. The conclusion of this study is that the venous plasma level of endothelin would seem to be a marker for severe disease, however, without any predictive value. PMID- 1879598 TI - Placental passage of azathiothymidine (AZT) during the second trimester of pregnancy: study by direct fetal blood sampling under ultrasound. AB - AZT-therapy during pregnancy is actually contraindicated. Two HIV-positive pregnant women who were due to have an induced abortion in the second trimester of pregnancy, were treated with AZT. Blood samples from mothers and fetuses and amniotic fluid samples were taken simultaneously. AZT crossed the placental barrier in the two patients. AZT and GAZT concentrations from the two fetuses were close to those obtained in the two women and in six non-pregnant volunteers. PMID- 1879599 TI - Prenatal diagnosis of an abdomino-pelvic hydrometrocolpos; a case report. AB - The authors describe a case of prenatal diagnosis of hydrometrocolpos performed at 35 weeks of ammenorhea. Diagnosis was based on fetal images of a rounded, solid, pelvic mass increasing rapidly, which evoked vaginal and uterine distension. No associated anomaly was found. This very unusual genital malformation required treatment at birth. This case shows that hydrometrocolpos can be evidenced by prenatal ultra-sonography allowing early treatment and prevention of complications. PMID- 1879600 TI - Idiopathic thrombocythemia and pregnancy; a case report. AB - A 28-year-old women with idiopathic thrombocytosis was treated with melphalan before pregnancy, which resulted in a normal platelet count. During pregnancy 80 mg acetylsalicyclic acid was given daily to prevent microcirculatory thrombotic complications. Fetal outcome was normal. PMID- 1879601 TI - Ultrasonic features of an ovarian cystohemangioma; a case report. PMID- 1879602 TI - Cerebral infarction after caesarean section due to heterozygosity for homocystinuria; a case report. AB - Eleven days after a caesarean section cerebral infarction was diagnosed. The underlying cause appeared to be a heterozygous form of homocystinuria. This inborn error in methionine metabolism increases the risk of premature arteriosclerosis, even in heterozygotes. The biochemical abnormalities can be prevented in most of the patients by treatment with vitamin B6 (pyridoxine). PMID- 1879603 TI - Basic fibroblast growth factor regulates the ability of astrocytes to support hypothalamic neuronal survival in vitro. AB - The putative neurotrophic effects of basic fibroblast growth factor (bFGF) were tested on embryonic hypothalamic neurons in dissociated cell culture. Basic FGF dramatically increased the survival of embryonic hypothalamic astrocytes plated on a poly-L-lysine (PLL) substrate. Basic FGF treatment also increased the number of hypothalamic neurons surviving in vitro; however, no neurotrophic effects were observed when astrocyte proliferation was prevented by using serum-free N2 medium or by using the mitotic inhibitor cytosine arabinoside. In contrast to effects when PLL was used as a substrate, bFGF reduced the survival of hypothalamic neurons plated on a confluent, contact-inhibited monolayer of astrocytes. This effect appears to be due to the direct actions of bFGF on astrocytes: treatment of confluent astrocytes with 5 ng/ml bFGF caused the protoplasmic astrocytes to develop a fibrillar morphology and reduced the ability of the astrocyte monolayer to promote neuronal survival after a further 24 hr in bFGF-free medium. It is concluded that in addition to its mitogenic effects, bFGF acts as a differentiation factor for protoplasmic astrocytes in vitro, and these morphological and functional changes may reflect the process of normal astrocytic development and response to brain injury in vivo. PMID- 1879604 TI - Occurrence of H1 subtypes specific to pronuclei and cleavage-stage cell nuclei of anuran amphibians. AB - Male pronuclei were induced in vitro by incubating the lysolecithin-permeabilized sperm nuclei of anuran amphibians Bufo japonicus and Xenopus laevis with the extracts from homologous eggs, and nuclear basic proteins were analyzed by two dimensional gel electrophoresis. By 5 min after the incubation, the sperm nuclei had completely lost sperm-specific proteins but possessed a whole set of nucleosomal core histones, except that H2A was mostly replaced by a putative H2A.X. The pronuclei did not possess any H1 histone subtypes found in differentiated somatic cell nuclei, but instead possessed components showing electrophoretic mobilities distinct from other H1 histones. This protein, designated as H1X, was regarded as an H1 subtype on the basis of its solubility in acids or salt and its lysine-rich amino acid composition. Peptide mapping using V8 protease further indicated that H1X is not a post-transcriptionally modified form of other somatic type H1 histones. By the time of chromosome condensation, pronuclear histones comprised H1X, H2A.X, H2B, H3, and H4. During embryonic development, H1X persisted in the nuclei up to the blastula stage, but mostly disappeared at the gastrula stage concomitant with the appearance of H1 subtypes of differentiated cells and the replacement of H2A.X by H2A. We conclude that H1X represents a maternally stored histone variant specific to nuclei of cleaving embryos. PMID- 1879605 TI - Xylose-linked proteoglycan synthesis does not have a primary role in the control of secretory cell differentiation in salivary glands. AB - Xylose-linked proteoglycans, particularly chondroitin sulfate proteoglycan, have been shown to play a significant role in the regulation of salivary gland morphogenesis. The purpose of this study was to determine if xylose-linked proteoglycans are involved in the regulation of differentiation of salivary gland secretory cells. Embryonic rat submandibular salivary gland rudiments were cultured for 120 hr in the presence or absence of 0.75 to 1.0 mM p-nitrophenyl beta-D-xylopyranoside (beta-D-xyloside), an inhibitor of xylose-linked proteoglycan assembly. beta-D-Xyloside has been shown to block submandibular gland morphogenesis (Thompson and Spooner, 1982). In the present study glandular morphogenesis was blocked in 93.3% of the rudiments cultured in the presence of beta-D-xyloside. However, secretory cell differentiation was observed in 71.4% of those rudiments in which morphogenesis had been inhibited. Biochemical evaluation confirmed that xylose-linked proteoglycan assembly had been inhibited by xyloside. These results indicate that while xylose-linked proteoglycans play a significant role in the control of salivary gland morphogenesis these molecules are not primary regulators for secretory cell differentiation within developing salivary glands. PMID- 1879606 TI - The bases for and timing of regional specification during larval development in Phoronis. AB - A fate map has been constructed for Phoronis vancouverensis. The animal pole of the egg gives rise to the apical plate in the hood of the actinotroch larva. The vegetal pole of the egg marks the site of gastrulation. During the initiation of gastrulation the cells of the animal pole of the embryo are directly opposite those at the vegetal pole of the embryo. The plane of the first cleavage always goes through the animal-vegetal pole of the egg. In about 70% of the cases the plane of the first cleavage is perpendicular to the future anterior-posterior axis of the actinotroch larva; in the remaining cases the plane of the first cleavage is either oblique with reference to, or occurs along, the future anterior-posterior axis of the larva. Following gastrulation catecholamine containing cells first make their appearance in the apical plate and gut cells first produce esterase. The timing of regional specification in these embryos has been examined by isolating animal or vegetal, anterior or posterior, or lateral regions at different time periods between the initiation of cleavage and gastrulation and examining their ability to differentiate. Animal halves isolated from early cleavage through late blastula stages do not gastrulate and do not form catecholamine-containing cells. When animal halves are isolated with endoderm during gastrulation, they differentiate catecholamine-containing cells. Vegetal halves isolated at the 8- to 16-cell stage gastrulate and form normal actinotroch larvae with esterase-positive gut and catecholamine-containing apical plate cells. When this same region is isolated at blastula stages it does not gastrulate and does not differentiate these cell types. Vegetal halves isolated during gastrulation subsequently form esterase-positive gut cells, but they do not form catecholamine-containing apical plate cells. When presumptive anterior, posterior, or lateral halves are isolated from early cleavage through blastula stages, each half forms a normal actinotroch larva. Lateral halves isolated during gastrulation also form normal larvae. Anterior halves isolated during late gastrulation differentiate only the anterior end of the actinotroch larva. These isolates have a hood with catecholamine-containing apical plate cells and the first part of an esterase-positive gut but lack the anlagen of the intestine and protonephridia. Posterior halves isolated during late gastrulation differentiate only the posterior end of the actinotroch which lacks a hood with catecholamine containing cells but has an esterase-positive gut, protonephridia, and the anlagen of the intestine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1879607 TI - Immunohistochemical localization of growth factors in fetal wound healing. AB - Fetal wound healing occurs rapidly, in a regenerative fashion, and without scar formation, by contrast with adult wound healing, where tissue repair results in scar formation which limits tissue function and growth. The extracellular matrix deposited in fetal wounds contains essentially the same structural components as that in the adult wound but there are distinct differences in the spatial and temporal distribution of these components. In particular the organization of collagen in the healed fetal wound is indistinguishable from the normal surrounding tissue. Rapidity of healing, lack of an inflammatory response, and an absence of neovascularization also distinguish fetal from adult wound healing. The mechanisms controlling these differing processes are undefined but growth factors may play a critical role. The distribution of growth factors in healing fetal wounds is unknown. We have studied, by immunohistochemistry, the localization of platelet-derived growth factor (PDGF), transforming growth factor beta (TGF beta), and basic fibroblast growth factor (bFGF), in fetal, neonatal, and adult mouse lip wounds. TGF beta and bFGF were present in neonatal and adult wounds, but were not detected in the fetal wounds, while PDGF was present in fetal, neonatal, and adult wounds. This pattern correlates with the known effects in vitro of these factors, the absence of an inflammatory response and neovascularization in the fetal wound, and the patterns of collagen deposition in both fetal and adult wounds. The results suggest that it may be possible to manipulate the adult wound to produce more fetal-like, scarless, wound healing. PMID- 1879608 TI - Rapid and slow mechanisms for loss of cell adhesiveness during fertilization in Chlamydomonas. AB - Although vegetative cells, gametes, and zygotes of the biflagellated alga Chlamydomonas bear flagella, only the flagella of mt+ and mt- gametes are adhesive. The molecules responsible for adhesiveness, mt+ and mt- agglutinins, are long rod-shaped glycoproteins displayed on the flagellar membrane. These flagellar agglutinins, which gametes use both as adhesion and signaling molecules during the early events of fertilization, are lost from the flagella during adhesion. Flagellar adhesiveness can be maintained, however, by recruitment and activation of preexisting, inactive agglutinins from the plasma membrane of the cell body (Hunnicutt et al, 1990, J. Cell Biol. 111, 1605-1616) unless the gametes of opposite mating types fuse to form zygotes. Upon cell fusion, flagellar adhesiveness is lost. In the studies presented here, we have employed an in vitro bioassay to measure agglutinins in both cell bodies and flagella at various times during gametogenesis, during fertilization, and after zygote formation. By use of the bioassay, which can detect agglutinins that are functionally inactive in vivo, we found that vegetative cells are devoid of agglutinins. These adhesion molecules appear only after gametogenesis is underway with the cell body agglutinins appearing first and then the flagellar agglutinins. Surprisingly, 30 min after zygote formation, when the zygotes' flagella are no longer adhesive, the flagellar agglutinin activity detectable with the bioassay remains high. One interpretation of these results is that zygotes continue to recruit agglutinins from the cell body to the flagella, but cell fusion abrogates activation of the agglutinins. Within 45-90 min after fusion both the cell body and flagellar agglutinins are lost and can be detected in the medium. These mechanisms, which render the zygotes nonadhesive to other zygotes and unmated gametes, contribute to the Chlamydomonas equivalent of a block to polyspermy. PMID- 1879609 TI - Spatial domains in the developing forebrain: developmental regulation of a restricted cell surface protein. AB - We have isolated a monoclonal antibody, mAb 52G9, that recognizes a 55-kDa cell surface protein restricted to the early embryonic rat forebrain and to placode derived structures. In the central nervous system (CNS), 52G9 immunoreactivity appears at Embryonic Day 11 (E11) in the rostral-most area of the telencephalon. It then spreads to the neuroepithelium of the telencephalon and basal diencephalon. Most strikingly, it appears at E14 in a distinct zone at the caudal end of the ventral diencephalic neuroepithelium. This area is sharply defined by strong 52G9 immunoreactivity bounded by unlabeled neuroepithelium. The pattern revealed by 52G9 is the first biochemical demonstration of spatial domains in the forebrain at a time prior to neuronal differentiation. By E18, 52G9 immunoreactivity has progressively disappeared from the forebrain; the glomerular layer of the olfactory bulb is the only 52G9-positive area in the CNS. The olfactory, otic, and hypophyseal placodes, which can be identified as early as E10, are also 52G9 positive as are their derivatives, the sensory epithelial of the nasal passage and inner ear, and also Rathke's pouch. The distribution and regulation of the 52G9 protein suggests that this novel cell surface molecule may be involved in the formation of spatial domains in the developing forebrain. PMID- 1879610 TI - Localization of insulin-like growth factor-1 mRNA in murine central nervous system during postnatal development. AB - Insulin-like growth factor-1 (IGF-1) is believed to play a role in the regulation of brain growth. The identity of cells responsible for its synthesis in the immature brain, however, has not been established. To identify potential sites of IGF-1 synthesis, in situ hybridization has been utilized to localize IGF-1 mRNA in the murine brain during the first postnatal month. Although IGF-1 mRNA was detected in all regions of the neonatal brain, there was considerable regional variation in the level of expression. Neurons were the principle sites IGF-1 mRNA expression and expression was typically restricted to one or two neuronal cell types within each region. In the cerebellar cortex, for example, only Purkinje cells hybridized to the IGF-1 probe. In contrast to gray matter, IGF-1 labeled cells were rarely found in presumptive white matter tracts of the forebrain. The hybridization signal was most prominent in regions where neurogenesis persisted after birth, including the cerebellum, olfactory bulb, and hippocampal complex. The timing of IGF-1 mRNA expression appeared to be temporally related to local neuronal proliferation. The number of labeled cells and intensity of hybridization signal was greatest during the first 2 postnatal weeks, a period of rapid neuronal proliferation in these regions. At the end of the first month, when neurogenesis had essentially ceased, IGF-1 signal strength had declined to background levels. The temporal and spatial pattern IGF-1 mRNA expression in the immature CNS was consistent with a role for locally produced IGF-1 in the regulation of brain development. PMID- 1879611 TI - Development of functional sex differences in the larynx of Xenopus laevis. AB - Three laryngeal properties associated with the production of masculine song- laryngeal muscle tension, fiber twitch type, and fiber recruitment--are markedly sexually dimorphic in adult Xenopus laevis frogs. To elucidate the pattern of sexual differentiation, tension and fiber recruitment in male and female larynges and fiber twitch type in male larynges were examined throughout postmetamorphic development. Masculinization of male laryngeal properties begins early in postmetamorphic development and continues until adulthood. In contrast, tension and fiber recruitment in females do not change after the end of metamorphosis. Laryngeal muscle tension and fiber type are gradually and progressively masculinized; the temporal pattern of masculinization is very similar for these properties. Fiber recruitment, on the other hand, appears to masculinize in a stepwise manner. Masculinization of all three properties is highly correlated with larynx weight in males. We have used this relation to divide postmetamorphic development into seven stages associated with key events in sexual differentiation. This staging scheme provides an important experimental tool for studying the hormonal regulation of sexual differentiation, the subject of the accompanying paper. PMID- 1879612 TI - Temporal constraints on androgen directed laryngeal masculinization in Xenopus laevis. AB - Temporal constraints on androgen regulated masculinization of three sexually dimorphic laryngeal properties--tension, fiber type, and fiber recruitment--were examined in Xenopus laevis frogs. Endocrine state was manipulated at PM0 when the larynx is similar in males and females, at PM2 when the larynx begins sexual differentiation, and at PM6 when sexual differentiation is complete. Removing the testes in developing males (PM0 or PM2) completely arrests laryngeal masculinization. Masculinization resumes when testosterone is replaced later in development (PM2 or PM6, respectively). Thus, testicular secretions, in particular androgens, are required for laryngeal masculinization. The ability of androgens to masculinize tension, fiber type, and fiber recruitment in developing and adult larynges was also determined. Five weeks of testosterone treatment in PM0 or PM2 males and females completely masculinizes laryngeal tension and fiber type, but only partially masculinizes fiber recruitment. However, fiber recruitment can be fully masculinized in PM6 males castrated at PM2. We conclude that androgen induced masculinization of tension and fiber type are not temporally constrained but that androgen induced masculinization of fiber recruitment is. Prolonged androgen treatment can override the temporal constraints on masculinization of the larynx. Testosterone treatment for more than 6 months fully masculinizes fiber recruitment in developing (PM0 or PM2) females. In addition, prolonged treatment (greater than 9 months) completely masculinizes tension, fiber type, and fiber recruitment in adult females; these properties were not fully masculinized by shorter (1-3 months) treatments in adult females. Testosterone induced masculinization in females is maintained for up to 8 months following testosterone removal; thus androgen effects are long lasting and possibly permanent. PMID- 1879613 TI - Monitoring by epifluorescence microscopy of organelle DNA fate during pollen development in five angiosperm species. AB - The fates of mitochondrial and plastid nucleoids during pollen development in six angiosperm species (Antirrhinum majus, Glycine max, Medicago sativa, Nicotiana tabacum, Pisum sativum, and Trifolium pratense) were examined using epifluorescence microscopy after double staining with 4',6-diamidino-2- phenylindole (DAPI) to stain DNA and with a potentiometric dye (either DiOC7 or rhodamine 123) for visualization of metabolically active mitochondria. From the pollen mother cell stage to the microspore stage of pollen development, mitochondria and plastids both contained DNA detectable by DAPI staining. However, during the further maturation preceding anthesis, mitochondrial DNA became undetectable cytologically in either the generative or the vegetative cell of mature pollen; even in germinated pollen tubes containing hundreds of metabolically active mitochondria undergoing cytoplasmic streaming, vital staining with DAPI failed to reveal mitochondrial DNA. By the mature pollen stage, plastid DNA also became undetectable by DAPI staining in the vegetative cell. However, in the generative cell of mature pollen the timing of plastid DNA disappearance as detected by DAPI varied with the species. Plastid DNA remained detectable only in the generative cells of pollen grains from species known or suspected to have biparental transmission of plastids. The apparent absence of cytologically detectable organelle genomes in living pollen was further examined using molecular methods by hybridizing organelle DNA-specific probes to digests of total DNA from mature pollen and from other organs of A. majus and N. tabacum, both known to be maternal for organelle inheritance. Mitochondrial DNA was detected in pollen of both species; thus the cytological alteration of mitochondrial genomes during pollen development does not correspond with total mtDNA loss from the pollen. Plastid DNA was detectable with molecular probes in N. tabacum pollen but not in A. majus pollen. Since the organelle DNA detected by molecular methods in mature pollen may lie solely in the vegetative cell, further study of the basis of maternal inheritance of mitochondria and plastids will require molecular methods which distinguish vegetative cell from reproductive cell organelle genomes. The biological effect of the striking morphological alteration of organelle genomes during later stages of pollen development, which leaves them detectable by molecular methods but not by DAPI staining, is as yet unknown. PMID- 1879614 TI - Temporal and spatial expression of the yellow gene in correlation with cuticle formation and dopa decarboxylase activity in Drosophila development. AB - The yellow (y) gene of Drosophila is required for the formation of black melanin and its deposition in the cuticle. We have studied by immunohistochemical methods the temporal and spatial distribution of the protein product of the y gene during embryonic and pupal development and have correlated its expression with events of cuticle synthesis by the epidermal cells and with cuticle sclerotization. Except for expression in early embryos, the y protein is only found in the epidermal cells and may be secreted into the cuticle as it is being deposited. The amount of y protein in various regions of the embryo and pupa correlates directly with the intensity of melanization over any section of the epidermis. Expression of the y gene begins in the epidermal cells at 48 hr after pupariation and is well correlated with the beginning deposition of the adult cuticle. At this stage the adult cuticle is unsclerotized and unpigmented and dopa decarboxylase levels, a key enzyme in catecholamine metabolism which provides the crosslinking agents as well as the precursors for melanin, is low. As a separate event 26 hr after the onset of y gene expression, the first melanin deposition occurs in the head bristles and pigmentation continues in an anterior to posterior progression until eclosion. This melanization wave is correlated with elevated dopa decarboxylase activity. Crosslinking of the adult cuticle also occurs in a similar anterior to posterior progression at about the same time. We have shown by imaginal disc transplantation that timing of cuticle sclerotization depends on the position of the tissue along the anterior-posterior axis and that it is not an inherent feature of the discs themselves. We suggest that actual melanization and sclerotization of the cuticle by crosslinking are initiated at this time in pupal development by the availability of the catecholamine substrates which diffuse into the cuticle. Intensity of melanization and position of melanin pigment is determined by the presence or absence of the y protein in the cuticle, thus converting the y protein prepattern into the melanization pattern. PMID- 1879615 TI - The dynamics of compartmentalization of embryonic muscle by extracellular matrix molecules. AB - In order to delineate the role of proteoglycans in muscle development, the immunohistological localization of glycosaminoglycans and proteoglycan core proteins was studied in embryonic chick leg at Hamburger-Hamilton stages (St.) 36, 39, 43, and 46, and at 2 weeks posthatching. A specific anatomical landmark was chosen (the junction between the pars pelvica and the pars accessoria of the flexor cruris lateralis muscle) in order to ensure the study of anatomically equivalent sites. Frozen cross sections were immunostained with monoclonal antibodies to chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, and keratan sulfate glycosaminoglycans; to the core proteins of muscle/mesenchymal chondroitin sulfate proteoglycan, dermatan sulfate proteoglycan, and basement membrane heparan sulfate proteoglycan; and to laminin and tenascin. Extracellular matrix zones corresponding to the endomysium, perimysium, epimysium, basement membrane, and myotendinous junction each show characteristic immunostaining patterns from St. 36 to St. 46 and have unique matrix compositions by St. 46. In some cases, there is a sequential or coordinate expression of epitopes, first in the epimysium, then the perimysium, and last in the endomysium. Dermatan sulfate proteoglycan is detected in the epimysium at St. 36, in the perimysium at St. 39 (there is no perimysium structure at St. 36), and is not detected in the endomysium until St. 43. A putative mesenchymal proteoglycan core protein (reactive to the monoclonal antibody MY-174) is detected at St. 39 in both epimysium and perimysium, but is not detected in the endomysium until St. 43. Keratan sulfate antibody immunostains epimysium at St. 39 and perimysium at St. 46, but is never detected in the endomysium. Some epitopes are expressed independently in each of the extracellular matrix zones: antibody to tenascin stains only a subset of the epimysium, at the myotendinous junction; and heparan sulfate proteoglycan and laminin are detected only in the endomysium. Between St. 36 and St. 39, the muscle/MY-174-reactive proteoglycan core protein staining decreases in intensity in the endomysium and becomes positive in the epimysium and perimysium. An inverse relationship is found between (1) the disappearance of muscle/MY-174-reactive proteoglycan core protein staining at the surface of myotubes from St. 36 to St. 39 and (2) the infiltration of laminin and heparan sulfate proteoglycan staining encompassing groups of myotubes (St. 36) to circumferential staining of all myotubes (St. 39).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1879616 TI - Pronuclear formation in starfish eggs inseminated at different stages of meiotic maturation: correlation of sperm nuclear transformations and activity of the maternal chromatin. AB - Changes in sperm nuclei incorporated into starfish, Asterina miniata, eggs inseminated at different stages of meiosis have been correlated with the progression of meiotic maturation. A single, uniform rate of sperm expansion characterized eggs inseminated at the completion of meiosis. In oocytes inseminated at metaphase I and II the sperm nucleus underwent an initial expansion at a rate comparable to that seen in eggs inseminated at the pronuclear stage. However, in oocytes inseminated at metaphase I, the sperm nucleus ceased expanding by meiosis II and condensed into chromosomes which persisted until the completion of meiotic maturation. Concomitant with the formation and expansion of the female pronucleus, sperm chromatin of oocytes inseminated at metaphase I enlarged and developed into male pronuclei. Condensation of the initially expanded sperm nucleus in oocytes inseminated at metaphase II was not observed. Instead, the enlarged sperm nucleus underwent a dramatic increase in expansion commensurate with that taking place with the maternal chromatin to form a female pronucleus. Fusion of the relatively large female pronucleus and a much smaller male pronucleus was observed in eggs fertilized at the completion of meiotic maturation. In oocytes inseminated at metaphase I and II, the male and female pronuclei, which were similar in size, migrated into juxtaposition, and as separate structures underwent prophase. The chromosomes in each pronucleus condensed, intermixed, and became aligned on the metaphase palate of the mitotic spindle in preparation for the first cleavage division. These observations demonstrate that the time of insemination with respect to the stage of meiotic maturation has a significant effect on sperm nuclear transformations and pronuclear morphogenesis. PMID- 1879617 TI - Homeogenetic neural induction in Xenopus. AB - Neural induction is known to involve an interaction of ectoderm with dorsal mesoderm during gastrulation, but several kinds of studies have argued that competent ectoderm can also be neutralized via an interaction with previously neuralized tissue, a process termed homeogenetic neural induction. Although homeogenetic neural induction has been proposed to play an important role in the normal induction of neural tissue, this process has not been subjected to detailed study using tissue recombinants and molecular markers. We have examined the question of homeogenetic neural induction in Xenopus embryos, both in transplant and recombinant experiments, using the expression of two neural antigens to assay the response. When ectoderm that is competent to be neuralized is transplanted to the region adjacent to the neural plate of early neurula embryos, it forms neural tissue, as assayed by staining with antibodies against the neural cell adhesion molecule, N-CAM. Transplants to the ventral region, far from the neural plate, do not express N-CAM, indicating that neuralization is not occurring as a result of the transplantation procedure itself. Because this response might be occurring as a result of interactions of ectoderm with either adjacent neural plate tissue, or with underlying dorsolateral mesoderm, recombinant experiments were performed to determine the source of the neuralizing signal. Ectoderm cultured in combination with neural plate tissue alone expresses neural markers, while ectoderm cultured in combination with dorsolateral mesoderm does not. We conclude that neural tissue can homeogenetically induce competent ectoderm to form neural tissue and argue that this induction occurs via planar signaling within the ectoderm, a mechanism that, in normal development, may be involved in interactions within presumptive neural ectoderm or in specifying structures that lie near the neural plate. PMID- 1879618 TI - Distinctive patterns of basic fibroblast growth factor (bFGF) distribution in degenerating and regenerating areas of dystrophic (mdx) striated muscles. AB - Mdx mice uniquely recover from degenerative dystrophic lesions by an intense myoproliferative (regenerative) response. To investigate a potential role of endogenous basic fibroblast growth factor (bFGF) in injury-repair processes, we investigated its localization in several striated muscles of mdx and control mice using immunofluorescence labeling with specific antibodies. Basic FGF was localized consistently to the myofiber periphery and nuclei of intact myofibers, as well as in single, dystrophin-positive cells in close association with the myofibers (potential myosatellite cells). In mdx mice, actively degenerating skeletal or cardiac muscle fibers presented intense cytoplasmic anti-bFGF staining prior to mononuclear infiltration. Small regenerating fibers in mdx skeletal muscle exhibited greater bFGF accumulation than adjacent larger myofibers. Strong nuclear anti-bFGF immunolabeling was frequently observed in mdx cardiac myocytes at the borders of necrotic regions. In agreement with differences in intensity of immunolabeling, extracts from slow-twitch muscles contained higher levels of bFGF compared to those from fast-twitch muscles, in both control and mdx mice. In addition, bFGF levels were consistently higher in extracts from all mdx tissues compared to those derived from their control counterparts. Our data suggest that bFGF participates in the degenerative and regenerative responses of striated muscle to dystrophic injury and also indicate a potential involvement of this factor with the physiology of different striated muscles. PMID- 1879619 TI - The Bobaths. PMID- 1879620 TI - The development of independent walking in children with cerebral palsy. AB - Electromyographic and kinematic data were collected during treadmill locomotion by normal infants and infants with cerebral palsy. Locomotor patterns of the infants with cerebral palsy were similar to those of normal infants during the stage of supported locomotion, but as they matured, some of the characteristics of the infant stepping pattern, such as synchronous muscle activity with excessive muscular co-contraction and short-latency reflexes at foot contact, were retained. The normal plantigrade features of adult gait did not develop in these children. PMID- 1879621 TI - Comparison of subjective and objective measures of movement performance of children with cerebral palsy. AB - The outcome of an eight-week period of additional occupational therapy, aimed at improving fine motor skills, was assessed by accelerometry and a rating scale based on the Erhardt Developmental Prehension Assessment. 10 children with cerebral palsy received their regular occupational therapy, while a similar group had an additional 30-minute session each day. No difference was found between groups at the end of the study. The difficulties of designing this type of project are discussed and the assessment methods described. PMID- 1879622 TI - Quantitative measurement of spasticity in children with cerebral palsy. AB - Spasticity was quantified in nine children with spastic diplegia, using a sinusoidal displacement of the foot at frequencies from 3 to 12Hz. Ankle-joint stiffness was separated into elastic (energy-storing) and viscous (energy dissipating) components. 'Path length' was used to represent the variation in stiffness over this frequency range. Compared with 11 unaffected children, a significant difference in path lengths was demonstrated for the children with spasticity. An age-dependent effect was demonstrated when path lengths of unaffected children were compared with those of 10 unaffected adults. A modified path-length measure is proposed which minimizes age dependency, yet enables detection of spasticity. Passive stiffness properties of unaffected adults showed higher elastic stiffness, viscosity and friction than unaffected children. A method was developed to evade the need for temporary nerve blocks to calculate inerital properties of the foot in persons with spasticity. PMID- 1879623 TI - Assessment of gestational age: modification of a simplified method. AB - A simplified method of six features for gestational age assessment was modified to include scored measurements for head circumference and mid-arm circumference, in order to improve reliability. The modified model had better correlation with gestational age than the simplified method, comparable accuracy to the Dubowitz system and was also more rapid. Preterm, low-birthweight, appropriate for gestational-age infants and term, low-birthweight, small for gestational-age infants were reliably identified by the model. PMID- 1879624 TI - Crying in !Kung San infants: a test of the cultural specificity hypothesis. AB - The pattern of crying and fretting behavior during the first two years is described for 46 !Kung San infants from a hunter-gatherer society in northwestern Botswana. Despite markedly different caretaking practices predisposing to quieter infants, crying and fretting were significantly greater during the first three months, and a peak pattern was present. Measurement of crying 'intensity' indicated that it was predominantly short and fretful. The results support the concept that the early peak pattern is not specific to infants in western industrialized societies, and may represent a behavior universal to the human species. The caretaking differences between societies primarily appear to affect crying duration rather than its frequency and pattern in early infancy. PMID- 1879625 TI - Infantile spasms treated with high doses of sodium valproate: initial response and follow-up. AB - A long-term follow-up study of 42 patients with West syndrome treated with high doses of sodium valproate is presented. Control of the hypsarrhythmic EEG pattern was achieved after two weeks for over three-quarters of the patients with sodium valproate doses of 100 to 300mg/kg/day. Recurrence of hypsarrhythmia was observed most often in patients treated with doses lower than 200mg/kg/day. Other types of seizures appeared in half of the patients followed beyond two years of age. Monotherapy throughout follow-up was possible for 30 patients. Autism occurred in only one infant, and 12 achieved normal mental status. The most common side effects were asymptomatic thrombocytopenia, vomiting and mild somnolence. Hepatic enzymes were not altered. PMID- 1879626 TI - Massage for very severe self-injurious behaviour in a girl with Cornelia de Lange syndrome. AB - The authors report the use of massage in a case of severe self-injurious behaviour in a girl with Cornelia de Lange syndrome, after failing to elicit a response to conventional management for 10 years. Improvement was dramatic and the possible mechanisms are discussed. PMID- 1879627 TI - Left unilateral neglect in a preschool child. AB - The authors present a case of transient left hemispatial inattention following traumatic brain injury in a three-year-old child. Computed tomographic scan revealed a small right frontal and a right temporo-parietal contusion. Stimuli were developed to quantify the response difference between hemifields in this pre literate child. Hemispatial inattention showed resolution at 19 days post-trauma and had completely resolved six months later. These findings suggest that right hemisphere systems subserve visually guided attention before six years of age. PMID- 1879628 TI - Head movements of visually impaired children. PMID- 1879629 TI - Functional sitting for children with cerebral palsy. PMID- 1879630 TI - Respiratory training in Duchenne dystrophy. PMID- 1879631 TI - Impact of the small bowel study on patient management. AB - Medical records of 528 consecutive patients who had a peroral small bowel examination or enteroclysis were reviewed. Clinical indications, efficacy of the small bowel examinations, and patient outcome were correlated to determine the impact of the small bowel examination on patient management. The most frequent indications were abdominal pain (19%), diarrhea (15%), obstruction (12%), bleeding (11%), postsurgical evaluation (10%), and assessment of Crohn's disease (8%). Two thirds of the studies (67%) were normal, and 33% of the examinations were abnormal, with similar results in all age groups. Small bowel obstruction (13%), miscellaneous results primarily including diffuse small bowel diseases (7%), adhesions (6%), and Crohn's disease (5%) were the most common abnormalities detected. The effects of small bowel studies on patient management were exclusion of serious pathology (67%), diagnosis that changed therapy (32%), and incidental findings (1%). Small bowel enteroclysis had a higher yield of positive examinations than the peroral small bowel examination, most likely due to patient selection. PMID- 1879632 TI - Transhepatic cholangiography in patients with suspected biliary disease and nondilated intrahepatic bile ducts. AB - Transhepatic cholangiography (THC) was performed in 107 patients who had nondilated intrahepatic bile ducts on computed tomography (CT) or ultrasound. The cholangiogram was diagnostic in 72 patients (67%). Thirty-one (43%) of the 72 diagnostic studies were abnormal and showed poor emptying, stones, or strictures. Twenty-three (21%) complications occurred, including two deaths. Sixteen patients experienced acute pain, requiring additional narcotics. There was one case of peritonitis and pancreatitis, and two of bacteremia. We compared our success and complication rates to those of endoscopic retrograde cholangiography (ERC) reported in the literature. We conclude that when a bile duct abnormality is clinically suspected, the incidence of pathology is sufficiently high to warrant direct visualization of the ducts in order to make an anatomic diagnosis, even if the intrahepatic ducts are not dilated. However, ERC has a better success rate and fewer complications than THC and it should be the initial invasive procedure. PMID- 1879633 TI - Congenital gallbladder duplication: preoperative diagnosis by ultrasonography. AB - Congenital gallbladder duplication, an uncommon but potentially complicating malformation, is rarely diagnosed preoperatively. A case in which the diagnosis was achieved by real-time ultrasonography is presented and correlated with hepatobiliary scintigraphy. The efficacy of these diagnostic modalities is discussed, and the available literature is reviewed. PMID- 1879634 TI - Angiographic management of massive hemobilia due to iatrogenic trauma. AB - Ten patients with massive hemobilia in shock or preshock status were treated with angiography. The hemobilia had been induced by iatrogenic trauma: biliary drainage in seven patients, and surgery, liver biopsy, and angiography in one patient each. Angiography was performed on all patients. Embolization was performed in nine, and in the one remaining patient, spasm of the right anterior hepatic artery and catheter manipulation injured the intima and obliterated the artery. In seven patients with hepatic artery pseudoaneurysm, gelfoam particles were injected in five, however, extravasation could not be prevented in four of these patients. Permanent embolic materials were added and complete hemostatis was obtained. Hemobilia never recurred in any patient. Emergency embolization should be considered as the initial treatment of choice for hemobilia and when pseudoaneurysms are discovered, they should be obliterated by permanent embolic materials. Moreover, tumor thrombus in the portal vein is not a contraindication for this procedure. PMID- 1879635 TI - Relation of size and number of common duct calculi to success of sphincterotomy and stone extraction. AB - Endoscopic sphincterotomy (ES) for common bile duct calculi (CBDC) was performed on 210 patients, and 190 of these were available for follow-up. One hundred seventy-three patients (91%) were successfully treated with ES alone, whereas 17 patients required operation. Stone size was of importance to attain complete clearance of CBDC as larger stones (greater than 1 cm) were significantly more difficult to extract endoscopically than smaller stones (p less than 0.01). A comparison between patients with one CBDC and those with two or more show a statistically significant difference in that the former group is easier to treat successfully (p less than 0.001). PMID- 1879636 TI - Alcoholic liver disease: value of the left-to-right portal vein ratio in its sonographic diagnosis. AB - A study group of 50 patients in whom the left portal vein diameter was equal to or greater than the right portal vein diameter (LPVD greater than or equal to RPVD) was prospectively compared on ultrasonography with a control group of 50 patients with LPVD less than RPVD. Clinical and laboratory data indicating chronic alcoholic liver disease (CALD) were observed with a significantly higher frequency in the study group than in the control group. It emerges from this study that LPVD greater than or equal to RPVD represents a useful ultrasonographic sign of CALD, corresponding to a relative enlargement of the left hepatic lobe compared with the right. PMID- 1879637 TI - Magnetic resonance imaging of macroscopic intrahepatic portal-hepatic venous shunts. AB - Direct communication between portal branches and the hepatic vein [macroscopic intra-hepatic portal-hepatic venous shunt (IPHVS)] is a rare entity. We have recently studied five patients with this condition. Magnetic resonance imaging (MRI) clearly demonstrated in each case the portal-hepatic venous shunt due to "flow void." Multiple diffuse shunts were present in one case and a solitary shunt was demonstrated in the others. The solitary shunt was either tubular, focally dilated or racemose in configuration. The MRI findings and clinical significance of this rare entity are discussed. PMID- 1879638 TI - MRI of hepatic iron deposition in patients with renal transplant. AB - Excess hepatic iron deposition was found in five of 15 (33%) renal transplant patients undergoing magnetic resonance (MR) screening for avascular necrosis of the femoral heads. Only one of these patients had overt liver disease. The number of prior blood transfusions was a significant factor for this deposition, whereas the age and sex of the patients, number and type of transplants, histocompatibility alleles (HLA), and years of hemodialysis and of chronic renal failure were not significant etiological factors. Liver/fat intensity ratios of less than 0.29 on T1-weighted images and ratios of less than 0.21 on T2-weighted images and a calculated T2 value of less than 35 ms were the best indicators of iron overload. Renal transplant patients are at great risk for excess hepatic iron deposition and MR imaging is a promising tool for the diagnosis of iron overload in this patient population. PMID- 1879639 TI - MR findings in liver adenomatosis. AB - Liver adenomatosis is a rare entity in which multiple hepatic adenomas (more than 10) occur in patients with no prior history of oral contraceptives or androgenic steroid use. This report describes findings of this entity on magnetic resonance imaging (MRI) and discusses the differential diagnosis of this disease. PMID- 1879640 TI - Nodular focal fatty infiltration of the liver in acquired porphyria cutanea tarda. AB - A case is reported of acquired porphyria cutanea tarda (PCT) due to administered valproate acid in an epileptic patient. Sonography (US) and computed tomography (CT) showed multiple nodular, well-defined lesions of the liver. Biopsy confirmed the diagnosis of focal fatty infiltration and revealed additionally the signs of hepatic involvement in PCT. Focal fatty infiltration should be considered in patients with multiple liver lesions if there is a predisposing condition. PCT can be a further cause of this type of infiltration. PMID- 1879641 TI - Amoebic liver abscess: rupture into retroperitoneum. PMID- 1879642 TI - Caroli disease: computed tomographic diagnosis. AB - Computed tomographic (CT) scan findings in patients with cavernous ectasia of the biliary tract (Caroli disease) have been described. Our patient had the isolated form of Caroli disease characterized by saccular dilatation of intrahepatic bile ducts and no evidence of portal hypertension. CT scan of the liver showed tiny dots with strong contrast enhancement within dilated intrahepatic bile ducts (the central dot sign). This finding when correlated with sonogram indicated portal radicles surrounded by dilated intrahepatic bile ducts. PMID- 1879643 TI - Portal vein thrombosis in Crohn's disease. AB - Thromboembolic complications of inflammatory bowel disease are a well-recognized occurrence. Portal vein thrombosis has been reported in patients with ulcerative colitis but to date has not been reported in patients with Crohn's disease. We present the first case of portal vein thrombosis in a patient with Crohn's disease. PMID- 1879644 TI - Pancreatic lymphangioma: CT, MRI, and angiographic features. AB - An unusual case of pancreatic lymphangioma presenting as a large mid-abdominal mass with sunburst pattern of calcification is herein described. The findings noted on computed tomography (CT), magnetic resonance imaging (MRI), and mesenteric angiography are illustrated. PMID- 1879645 TI - Immunoscintigraphy of colorectal carcinoma utilizing 111In-labeled monoclonal antibody conjugate CYT-103. AB - Twelve presurgical patients with colorectal carcinoma received a single intravenous infusion of 0.5-20.0 mg of the radiolabeled monoclonal antibody conjugate CYT-103. This product is an immunoconjugate of B72.3 labeled with Indium-111 (111In). Patients underwent preoperative gamma camera imaging and computed tomographic (CT) scanning of the abdomen and pelvis. Fifteen intraabdominal sites of tumor were found at surgery. Monoclonal antibody imaging detected 87% of these lesions, whereas CT of the abdomen and pelvis detected 47%. Monoclonal antibody imaging identified tumor in 27% of the patients in which CT did not identify any sites of tumor. The results of this study indicate that monoclonal antibody imaging using [111In]CYT-103 is useful for the preoperative evaluation of colorectal carcinoma patients and the results are complimentary to CT of the abdomen and the pelvis. PMID- 1879646 TI - Lymphoma of the appendix. AB - A rare case of appendiceal lymphoma in a patient who presented with lower gastrointestinal bleeding is reported. The findings on double-contrast barium enema, computed tomography (CT), and ultrasound are described and the clinical features of the few previously reported cases of appendiceal lymphoma are discussed. PMID- 1879647 TI - Transrectal ultrasound and computed tomography in preoperative staging of lower rectal adenocarcinoma. AB - A comparison of transrectal ultrasound (TRUS) and computed tomography (CT) for staging of rectal carcinoma was performed. Thirty-two patients were examined by TRUS and 30 by CT. The results of these preoperative examinations were compared with postoperative histopathological findings. TRUS had an accuracy of 81% and it predicted perirectal tumor growth with a sensitivity of 90% and a specificity of 67%, whereas the corresponding figures for CT were 52%, 67%, and 27%. These findings indicate that TRUS is more efficient than CT in staging local tumor growth in rectal cancer. Neither technique, however, can reliably identify lymph node metastases, since no correlation was found between lymph node size as observed on CT and TRUS and tumor involvement as evaluated histopathologically. PMID- 1879648 TI - Computed tomography in adult intussusception. AB - Computed tomographic (CT) changes of intussusception include the early target mass with fascial planes around the mass retained; with progress and bowel wall thickening, the characteristic mass with layering effect occurs (i.e., areas of high density with curvilinear low-density zones). Traction on the associated mesenteric vasculature may be noted. Scattered air-fluid levels indicate the associated presence of bowel obstruction. As edema of the bowel progresses, the layering effect is obscured, and the compromised bowel assumes an amorphous shape surrounded by intraperitoneal fluid. The presence of intramural air is indicative of vascular compromise of the intussuscepting bowel. PMID- 1879649 TI - Invasive squamous cell carcinoma of the anus arising in condyloma acuminatum: CT demonstration. AB - We present two cases of invasive squamous cell carcinoma of the anus complicating long-standing anal condyloma acuminatum. The computed tomographic (CT) findings are reviewed, and the increasing importance of malignant transformation of anal condylomas is discussed. PMID- 1879650 TI - Seasonal changes in plasma prostaglandin F2 alpha and sex hormones in the male water frog, Rana esculenta. AB - Prostaglandin F2 alpha (PGF2 alpha), progesterone, androgens (testosterone + dihydrotestosterone), and 17 beta-estradiol were measured in the plasma of male frogs, Rana esculenta, by radioimmunoassays. Plasma concentrations of PGF2 alpha were higher from October to December and peaked in March (prereproduction) and in June (postreproduction). Plasma progesterone levels were relatively low but showed an increase from October to December and in June. Plasma androgen titres rapidly increased in early spring, started to fall during the reproductive period (May), and were lowest in July. 17 beta-Estradiol levels peaked in March and in June. The annual profile of the plasma PGF2 alpha levels was positively correlated with those of progesterone and androgens, while it was not correlated to the estradiol plasma pattern, except in March and June. The increase in plasma PGF2 alpha in the autumn may be related to gonadal recovery. The simultaneous increases in PGF2 alpha and 17 beta-estradiol, both in March and June, suggest a PGF2 alpha-dependent estradiol synthesis, a possibility also supported by the increased plasma 17 beta-estradiol previously observed in PGF2 alpha-treated postreproductive females. The effects of captivity and castration on plasma PGF2 alpha concentrations were also studied during the annual cycle. Captivity was associated with a reduced PGF2 alpha titre, while castration did not modify prostaglandin synthesis, which may point to an extragonadal source of plasma PGF2 alpha. PMID- 1879651 TI - Sex steroid profile and plasma vitellogenin during the annual reproductive cycle of the crested newt (Triturus carnifex Laur.). AB - The annual reproductive cycle of the crested newt, Triturus carnifex, has been studied in the field. Temperatures, rainfall, humidity, and photoperiod were recorded throughout the year. Adult male and female newts were sampled monthly; snout vent lengths, crest heights of males, and body ovarian, oviducal, testicular, and abdominal gland weights were recorded. Plasma samples were assayed for androgen, estradiol-17 beta, and progesterone by radioimmunoassay and for vitellogenin by enzyme-linked immunosorbent assay. Air, deep water, water surface, and soil temperatures were low from October to March, but increased in April and May without consistent summer variations. Ovarian and oviducal weights increased in October to reach maximum values between January and March (reproductive period). Crest height and abdominal gland weight in males mirrored the ovarian and oviducal pattern, while testicular weights were maximal in October and November. In females, plasma androgens were high during the reproductive period, and plasma estradiol peaked sharply in March, while plasma progesterone changed little. In the males plasma androgen and estradiol concentrations were similar to those of females, while plasma progesterone was significantly correlated with the cycle in testicular weight. In both sexes androgens showed a significantly negative correlation with air and water surface temperature. Plasma vitellogenin peaked in March but it did not correlate with either ovarian weight or plasma estradiol concentrations. These data support and confirm those previously reported for newts under laboratory conditions. The negative correlation between androgens and temperature suggests that this hormone may trigger the reproductive process. Moreover the correlations between plasma progesterone and testicular weight may indicate that this hormone is involved in male newts reproduction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879652 TI - Circadian time dependence of erythropoietic and respiratory responses of Indian garden lizard, Calotes versicolor, to mammalian urinary erythropoietin and thyroxine. AB - The circadian stage-dependent effects of mammalian urinary erythropoietin (Ep) and thyroxine (T4) on tissue energy metabolism (in vivo and in vitro) and erythropoiesis were examined in the Indian garden lizard. Both T4 and Ep increased erythropoiesis and also affected hepatic and muscle energy metabolism. Although both treatments increased circulating RBC count, irrespective of the timing of the treatment, the maximum erythropoietic stimulation was achieved only in the late photophase (9 hr after light onset, HALO). Hepatic oxygen uptake was significantly elevated at 3 and 9 HALO following in vivo Ep administration and 3, 9, and 15 HALO following in vivo T4 injection. In contrast, in vitro addition of either Ep or T4 to hepatic homogenates of untreated lizards significantly elevated respiratory rate, irrespective of the time of tissue collection. The rate of muscle tissue respiration was statistically elevated when Ep was administered in vivo at 9 and 15 HALO. The oxygen uptake was stimulated by T4 only at 15 HALO. While in vitro addition of Ep to tissue homogenates significantly depressed the respiratory rate of muscle collected at 3 HALO, addition of T4 stimulated oxygen uptake by the muscle tissue collected at 9 and 15 HALO. It is concluded that the effectiveness of Ep or T4 largely depends upon the phase of the organism's circadian system(s). PMID- 1879653 TI - Changes in cortisol and thyroid hormone concentrations during early development and metamorphosis in the Japanese flounder, Paralichthys olivaceus. AB - Both cortisol and thyroid hormones were detected in newly fertilized eggs of the Japanese flounder, Paralichthys olivaceus. Mean cortisol levels ranged around 2.5 ng/g wet weight. Cortisol concentrations declined to about one-tenth of their initial levels by 2 days before hatching. The concentrations of triiodothyronine (T3; 7 ng/g) were greater than those of thyroxine (T4; 0.4 ng/g). The T3 levels decreased gradually in the eggs until the time of hatching and then decreased rapidly to undetectable levels within 2 days, whereas T4 remained at more or less constant levels during early development. The significance of the "selective" clearance of the three hormones from eggs remains unclear. Tissue concentrations of cortisol during premetamorphosis were about 4 ng/g and increased to a peak level of 11 ng/g at climax. After climax, cortisol declined by 50%. The changes in thyroid hormone levels were in parallel with the changes in cortisol. T4 remained below 1 ng/g during prematamorphosis but increased gradually during prometamorphosis, reaching peak levels (12 ng/g) during metamorphic climax, and then declined by approximately 50%. T3 remained at low levels through most of the metamorphosis. Histologically, the interrenal tissue was activated during the metamorphosis. The coincident increases in cortisol and thyroid hormones support previous results of a synergistic action of both hormones during metamorphosis in the flounder. PMID- 1879654 TI - Plasma melatonin levels in Japanese quail exposed to dim light are determined by subjective interpretation of day and night, not light intensity. AB - Plasma melatonin levels were measured in male Japanese quail exposed to lighting schedules consisting of combinations of bright light (2000 or 1500 lx), darkness, or dim light (2 lx) or to constant dim light. Melatonin levels in dim light were dependent upon the relative intensity of accompanying phases, being significantly higher when dim light was subjective night than when it was subjective day. There was no significant melatonin rhythm in constant dim light, even on the first day of constant dim light exposure. Melatonin levels were intermediate when dim light was accompanied by both bright light and darkness. These results indicate that melatonin secretion in birds does not depend solely on light intensity. Furthermore, these results suggest that the avian circadian system may be more sensitive to environmental cues than its mammalian counterpart. PMID- 1879655 TI - Cuticle deposition and ecdysteroid titers during embryonic and larval development of the argasid tick Ornithodoros moubata (Murray, 1877, sensu Walton, 1962) (Ixodoidea:Argasidae). AB - Timing of embryonic and larval molts at the ultrastructural level and presence of ecdysteroids (ES) during embryonic and larval development of the argasid tick Ornithodoros moubata were studied. Embryonic "cuticles" A, B, and C were deposited 24-30 hr, 48-56 hr, and 6 days after oviposition, respectively. Deposition of the larval cuticulin layer started on Day 8 of embryonic development and procuticle deposition continued after hatching until apolysis of the larval cuticle 40 hr posthatch. Plaques of cuticulin formed on tips of microvilli 48-56 hr after hatching and procuticle was deposited until after ecdysis. Radioimmunoassay (RIA) was used to determine the ES titer in methanolic extracts of various ages of embryos and larvae. No peaks of RIA-positive material were detected during deposition of envelopes A, B, and C. However two peaks of ES were observed during embryonic development, one which coincided with the shortening of the germ band and a second which coincided with the deposition of the larval epicuticle on Day 8. During larval development, a peak of ES was observed on Day 3 (48-56 hr posthatch) and was correlated with nymphal epicuticle deposition. HPLC-RIA revealed that these last two peaks consisted mainly of 20 hydroxyecdysone together with a small quantity of ecdysone. Conjugated RIA positive material was present in freshly laid eggs and an augmentation of this esterase hydrolysable material was noted at the appearance of each ES peak. Thus the embryos did not appear to be hydrolyzing the maternal apolar conjugates to release ES during embryonic development; on the contrary, they appeared to be conjugating the newly synthesized hormones. PMID- 1879656 TI - Patterns of breeding in two species of agamid lizards in the arid subtropical Pilbara region of Western Australia. AB - The reproductive cycles of two annual species of desert agamids have been studied over a 7-year period in the arid Pilbara region of Western Australia in an effort to identify proximate factors influencing their disparate modes of reproduction. Amphibolurus (= Ctenophorus) nuchalis breeds regularly in spring (September October in the southern hemisphere) in the southern parts of its range, following reliable winter rainfall which stimulates insect abundance sufficient to sustain their reproductive effort. In the Pilbara region, however, winter rainfall is small and erratic and total rainfall is influenced primarily by summer cyclones. A. nuchalis breeds in spring in the Pilbara in those years when winter rain is substantial, but defers breeding until after the cyclonic rains in late summer in very dry years. The physiological condition of A. nuchalis in spring in such years is depressed, suggesting that resources sufficient to sustain the reproductive effort are lacking, but they show no obvious signs of stress. In years where adequate winter rainfall has been followed by early cyclonic rains, the A. nuchalis population breeds continuously for a 6-month period between October and March of the following year. Although circulating levels of androgens rise significantly in spring in the second species, A. caudicinctus, the gonads remain regressed and this species displays an inflexible pattern of reproduction, breeding only following cyclonic rain in March-April each year, no matter what rains fall in the preceding winter. A. nuchalis thus appears to be an opportunistic vernal breeder, limited only by the availability of resources, whereas A. caudicinctus, which apparently displays the greater reproductive effort of the two species, has a typical aestival pattern of breeding which is uniquely attuned to the enormous burst of productivity occurring in this arid region following the substantial and predictable summer cyclonic rains. Although environmental temperature has often been seen as the primary factor determining reproductive cycles in reptiles, this study suggests that temperature is a necessary but not a sufficient condition for successful reproduction and that the availability of adequate resources may assume an overriding importance, especially in arid habitats where annual rainfall may be highly unpredictable. PMID- 1879657 TI - Steroid hormone binding in the Harderian gland of birds: characteristics of the androgen, estrogen, and progestin receptors of Anas platyrhynchos and Gallus domesticus. AB - A series of experiments was carried out in immature female chicks and ducks to establish whether the avian Harderian gland contains specific receptors for sex steroids. Cytosol preparations of Harderian glands were submitted to hormone saturation analysis using radiolabeled estradiol, ORG-2058, and dimethylnortestosterone as ligands. In addition, the sedimentation characteristics of the hormone-receptor complexes were studied by ultracentrifugation of linear sucrose gradients. The presence of high affinity binding sites for estrogens (Kd = 2.4 and 1.6 nM), progestins (0.8 and 1.0 nM), and androgens (1.0 and 1.0 nM) was indicated in the chick and duck glands, respectively. The sedimentation coefficients were 7-7.5 S, 7-8 S, and 8 S for estrogen, progestin, and androgen receptor-ligand complexes, respectively. The concentration of the androgen receptor was significantly higher in chick than in duck Harderian glands whereas the estrogen and progestin receptor concentrations were similar in both species. A striking finding was the presence of progestin receptors, which apparently do not exist in the glands of many mammals. Priming with estrogens did not modify the concentration of ORG-2058 binding sites in either species studied, indicating that gland progestin receptor is not estrogen regulated. Overall the data suggest intracellular mechanisms whereby circulating gonadal hormones regulate avian Harderian gland function. PMID- 1879658 TI - Avian LHRH during embryonic development: measurement by competitive ELISA with a monoclonal antibody. AB - A mouse monoclonal antibody directed against chicken Gln8-luteinizing hormone releasing hormone (cLHRH-I) was developed and characterized. This antibody was used for the development of a competitive microtiter plate enzyme-linked immunosorbent assay for avian LHRH. The assay was validated for use with tissue and was used at a working range between 5 pg and 10 ng per sample. Using this procedure, cLHRH-I and II were assayed in whole brain extracts of Japanese Quail embryos. Samples were taken at regular intervals between Day 6 of incubation through Day 1 posthatch. There were 10 samples taken at each age with 2 replicates of the entire sampling regime. Data from males and females were pooled. LHRH concentrations were low, then rose to higher levels (15 pg/mg tissue) between Days 10 through 13 and decreased thereafter. These changes are likely to be correlated with the activation of the hypothalamic-pituitary-gonadal axis. This is particularly apparent in later embryonic development. PMID- 1879659 TI - The acute effects of alteration in the dietary concentrations of carbohydrate, protein, and lipid on plasma T4, T3, and glucose levels in rainbow trout, Oncorhynchus mykiss. AB - The acute (4 hr) postprandial effects of a single isocaloric meal varying in the proportions of either carbohydrate (C)/lipid (L), C/protein (P), or L/P on plasma levels of glucose, T4 (L-thyroxine) and T3 (3,5,3'-triiodo-L-thyronine) were examined in rainbow trout starved for 3 days. Relative to starved controls, plasma T3 was generally uninfluenced by feeding but was increased by diets containing the highest C/L and P/L ratios. Plasma T4 was elevated only in instances where there was sufficient available dietary C to raise plasma glucose to at least 126 mg/100 ml. High dietary P or L levels in combination with low C levels and a postprandial plasma glucose level below 126 mg/100 ml did not elevate plasma T4. For fish fed an acaloric alpha-cellulose diet, plasma T4 was unchanged indicating that gastric filling alone does not contribute significantly to the T4 surge. It is concluded that the previously demonstrated postprandial elevation in plasma T4 is determined mainly by the level of dietary C and the available glucose, and not by P, L, total caloric content, or bulk properties of the ingesta. PMID- 1879660 TI - Effects of stanniectomy and experimental hypercalcemia on plasma calcium levels and calcium influx in American eels, Anguilla rostrata, LeSueur. AB - Intraperitoneal injection of CaCl2 in intact, sham-stanniectomized, and stanniectomized American eels, Anguilla rostrata (LeSueur), resulted in a rapid elevation of plasma calcium level which was more marked and of longer duration in the stanniectomized eels. The same treatment reduced whole body calcium influx (JinCa2+) in the intact and sham-stanniectomized groups for the first but not the second of two 4 hr flux periods. The same treatment did not affect JinCa2+ in the stanniectomized eels. We conclude that calcium loading in eels with intact stannius corpuscles (CS) results in the release of a CS hormone (stanniocalcin) which inhibits the uptake of calcium from the environment and that this facilitates the return to normocalcemia. These data provide direct evidence for a relationship between stanniocalcin release in vivo and a hypocalcemic response and the first evidence concerning the functional turnover time of this hormone. PMID- 1879661 TI - Insulin binding to liver plasma membranes of coho salmon during smoltification. AB - Smoltification of coho salmon (Oncorhynchus kisutch) is accompanied by characteristic changes in plasma insulin levels, with peak values attained at the beginning of the transformation period (the parr to transitional stage). To relate these changes to responsiveness of target tissues a study was made of binding of homologous insulin to liver plasma membranes in coho salmon undergoing the parr-to-smolt transformation. In general, parameters of specific insulin binding to the preparations of liver plasma membranes were similar to same parameters of insulin binding in other teleost fishes investigated so far and in mammals. The total binding capacity of insulin, a value that reflects the total number of binding sites, was higher in smolts than in parrs. The number of high affinity, low capacity binding sites in the liver membranes steadily increased as smoltification progressed, reached a maximum in early smolts, and declined thereafter. Another increase in the numbers of high affinity binding sites was observed in smolts transferred from fresh water to seawater. The specific binding of insulin in salmon at particular developmental stages was probably related to, and determined by, both the quantity of binding sites and their relative affinities. In smolts the highest levels of specific binding of insulin to the liver plasma membranes were coincident with the low levels of insulin in the peripheral blood that passed through the liver. PMID- 1879662 TI - Calcitonin gene-related peptide immunoreactivity in a crustacean Nephrops norvegicus and correlation with calcitonin. AB - Immunoreactive calcitonin-gene-related peptide (ir-CGRP) was detected in the crustacean Nephrops norvegicus. High levels of ir-CGRP were present in the foregut and hepatopancreas (3 +/- 0.7 and 4.6 +/- 1.0 micrograms eq per 100 mg of fresh organ, respectively). Molecular sieving of acidic extracts of anterior gut of Nephrops norvegicus showed a high molecular weight immunoreactive peptide in the range 15,000 to 25,000 Da. Immunoreactivity related to salmon calcitonin was present in the high molecular weight fraction. PMID- 1879663 TI - Plasma growth hormone levels during sexual maturation in diploid and triploid rainbow trout (Oncorhynchus mykiss). AB - Plasma growth hormone concentrations were determined in diploid and triploid rainbow trout of both sexes during sexual maturation. Diploid females grow large ovaries, whereas triploid female trout show no ovarian development. The plasma growth hormone concentration in triploid female trout remained low and unchanged throughout the study, whereas it rose slightly, but significantly, in the diploid females that matured, but not in those that remained immature. On the other hand, triploid males do develop tests like their diploid counterparts. In both groups spermiation was accompanied by a steady rise in the plasma growth hormone concentration. The results suggest that the elevated growth hormone concentration in mature male trout was a consequence not of reproduction per se, but of the loss of condition that accompanied spawning. This hypothesis was supported by the results from the females. Apart from a temporary loss in the mature diploids caused by stripping of the eggs, female trout did not lose condition, neither did they show any change in the plasma growth hormone concentration during the period when they ovulated. These results suggest that it was the nutritional insufficiency accompanying reproduction in male fish that caused the elevation in growth hormone concentration. In fact, a strong negative correlation between the plasma growth hormone concentration and the condition factor of the fish was observed. PMID- 1879664 TI - Ecdysteroids in relation to the molt cycle of the American lobster, Homarus americanus. II. excretion of metabolites. AB - Ecdysteroid (Ecd) excretion patterns were followed during the molt cycle of adult male and female lobsters. Homarus americanus. Urine was the major route of Ecd elimination, amounting to greater than or equal to 96% of the excreted radioimmunoassay activity for all molt stages. The other identified route of Ecd elimination from the hemolymph was the feces, which accounted for the remaining 4% of the total Ecd excretion. High polarity metabolites (HP), including 20,26 dihydroxyecdysone (2026E) and 20-hydroxyecdysonoic acid (20EA), were the major types of Ecds found in the urine. Other urinary Ecd components included 20 hydroxyecdysone (20E), ecdysone (E), and ponasterone A (P). The major portion of urinary HP was composed of conjugates of 2026E, 20E, E, P, and other unidentified metabolites. The fecal Ecds were predominately HP and apolar metabolites. Apolar fecal Ecds were hydrolyzable to release 20EA, 2026E, 20E, E, P, and other metabolites. By means of intubation, [3H]E was placed directly into the cardiac stomach of lobsters. The gut pathway formed an apolar conjugate of [3H]E which was found exclusively in the feces. Lobsters are therefore capable of excreting ingested Ecds without absorption. PMID- 1879665 TI - Effect of background color and low temperature on skin color and circulating alpha-MSH in two species of leopard frog. AB - Circulating levels of alpha-melanocyte stimulating hormone (alpha-MSH) in two species of leopard frog, Rana pipiens and R. chiricahuensis, were measured by radioimmunoassay to reveal the correlation between skin color change induced by background color and by low temperature. High levels of alpha-MSH were found in both species of frog on a black background, but R. chiricahuensis had eight times higher levels than R. pipiens, R. chiricahuensis also exhibited the ability to darken its ventral surface, whereas the ventral surface of R. pipiens remained white. Neither skin color nor plasma alpha-MSH of R. pipiens was affected by cold. Low temperature did, however, darken dorsal and ventral skin of R. chiricahuensis in vivo, which corresponded to increased levels of plasma alpha MSH. Dorsal and ventral skin of R. chiricahuensis, in vitro, darken in a dose dependent manner to alpha-MSH, but not to cold. PMID- 1879666 TI - Distribution and characterization of immunoreactive growth hormone (GH) in the pituitary of the frog Rana ridibunda using an antiserum against purified bullfrog GH. AB - The presence of growth hormone (GH) in the pituitary of the frog Rana ridibunda was investigated using an antiserum raised against purified bullfrog GH. The immunofluorescence technique revealed that GH-containing cells are exclusively located in the dorsal area of the distal lobe of the pituitary. The relative abundance of these GH-positive cells, which correspond to acidophilic type 2 cells, was 18 +/- 1% of the total population of endocrine cells of the pars distalis. Frontal sections of the distal lobe indicated that GH-producing cells are distributed in an arc of a circle occupying all of the dorsal part of the lobe. At the electron microscopic level, GH-immunoreactive material was sequestered in large polymorphic granules (200-700 nm). GH was quantified in R. ridibunda pituitary extracts using a radioimmunoassay for bullfrog GH. The displacement curves obtained with serial dilutions of pars distalis extracts were not strictly parallel to the standard curve made with purified bullfrog GH. In contrast, Western blot analysis revealed that GH from R. ridibunda had a molecular weight (22 kDa) similar to that of bullfrog GH. In the pars distalis, the apparent amount of GH was 0.61 +/- 0.14 microgram per lobe, corresponding to 0.92 +/- 0.17% of total proteins in the extracts. In contrast, frog neurointermediate lobe or hypothalamus did not contain significant concentrations of immunoreactive GH (less than 0.006% of total proteins in the extracts). Taken together, these results validate the use of an antiserum to bullfrog GH to investigate the regulation of GH secretion in R. ridibunda. PMID- 1879667 TI - Circadian rhythms of melatonin secretion from superfused goldfish (Carassius auratus) pineal glands in vitro. AB - A flow-through, whole-organ culture (superfusion) system was developed, and goldfish pineal glands were maintained at 25 degrees under light-dark (LD) 12:12 cycles, reversed LD 12:12 cycles, continuous dark (DD), or continuous light (LL) conditions for 48 hr. Under LD 12:12 and reversed LD 12:12 cycles, superfused pineal glands showed a rhythmic melatonin secretion: Scotophase was associated with high titers and photophase with low titers. The melatonin secretion rhythms persisted for two cycles under DD conditions, whereas nocturnal rises were suppressed under LL conditions. After the transition from LL to DD conditions on the third day, melatonin showed a nocturnal increase. These results indicate that melatonin secretion from the superfused goldfish pineal gland is directly photosensitive and that the goldfish pineal gland harbors a circadian oscillator which generates melatonin secretion rhythms. PMID- 1879668 TI - In vitro metabolism of progesterone by peripheral blood of rock hyrax (Procavia capensis). AB - In vitro metabolism of progesterone by hyrax whole blood, erythrocytes, or plasma in the presence or absence of NADPH was investigated. In the presence of NADPH, whole blood metabolized progesterone to 5 alpha-pregnanedione and 5 beta pregnanedione, but in the absence of NADPH, only 5 beta-pregnanedione was produced. Erythrocytes in the presence and the absence of NADPH produced only 5 beta-pregnanedione. The plasma component of blood metabolized progesterone to give 5 alpha-pregnanedione, but only in the presence of NADPH. These results suggest the presence of two types of steroid reductases found in plasma and erythrocytes. The extent of progesterone metabolism by the blood of animals in different reproductive states is in the order of pregnant females greater than nonpregnant females greater than male. PMID- 1879669 TI - Cloning of a turkey prolactin cDNA: expression of prolactin mRNA throughout the reproductive cycle of the domestic turkey (Meleagris gallopavo). AB - A cDNA-encoding turkey prolactin (PRL) has been isolated from a turkey pituitary library. The 953-base pair cDNA clone contains a 229-amino acid open reading frame which consists of a 30-amino acid signal peptide followed by a 199-amino acid mature PRL. The deduced amino acid sequence of turkey PRL shows greater than 90% homology to chicken PRL and 54-78% homology to other mammalian prolactins. A mRNA of 1100 nucleotides was detected in total RNA extracted from turkey pituitaries. Levels of PRL mRNA increased approximately 10-, 20-, and 100-fold in photostimulated, laying, and incubating hens, respectively, relative to that found in nonphotostimulated hens. The corresponding increases in plasma PRL levels were 2-, 5.5-, and 50-fold and in pituitary PRL content were 2-, 4-, and 13.4-fold, respectively. The transition from incubation to the photorefractory phase resulted in a 10-fold reduction in PRL mRNA, a 3.7-fold decrease in pituitary PRL, and a dramatic 50-fold decrease in plasma PRL. The changes in the abundance of pituitary PRL mRNA appear to be related to the changes in PRL releasing activity observed at each of the reproductive stages. This study provides the first characterization of pituitary PRL mRNA and its comparison with plasma and pituitary PRL levels during the avian reproductive cycle. PMID- 1879670 TI - Circadian regulation of synthesis of ecdysteroids by prothoracic glands of the insect Rhodnius prolixus: evidence of a dual oscillator system. AB - Rhythmic synthesis of moulting hormones (ecdysteroids) by prothoracic glands (PGs) of the insect Rhodnius prolixus during the last larval instar was studied in vitro following explantations every 4-5 hr for up to 96 hr. Ecdysteroid synthesis was measured by radioimmunoassay as the quantity of ecdysteroid produced during 4 hr in vitro. A massive daily rhythm is seen, with synthesis at night being three- to fivefold higher than during the day. This rhythm of ecdysteroid synthesis by PGs free-runs in continuous darkness with a temperature compensated period length close to 24 hr and is therefore controlled by a circadian system. This is the first report of circadian regulation of synthesis of an invertebrate hormone. The synthesis rhythm also free-runs in continuous light, but with an inverted phase and shorter period length. It is argued that the circadian system controlling synthesis comprises two oscillators which free run in antiphase, occupy different anatomical locations, and are coupled by a humoral factor, possibly prothoracicotropic hormone. The ecdysteroid synthesis rhythm in PGs appears to drive the previously reported circadian rhythm in the haemolymph ecdysteroid titre. It is concluded that the circadian system controlling synthesis of ecdysteroids constitutes a pacemaker which drives various rhythms in the target cells of ecdysteroids via the rhythm in the haemolymph titre. Ecdysteroids are viewed as "hormonal Zeitgebers," imposing temporal order on development. PMID- 1879671 TI - Plasma levels of luteinizing hormone and androgens in relation to age and breeding status among cooperatively breeding Australian magpies (Gymnorhina tibicen Latham). AB - Plasma levels of luteinizing hormone (LH), testosterone (T), and 5 alpha dihydrotestosterone (DHT) were measured in relation to age and social/breeding status among free-living male Australian magpies. Magpies live in territorial groups of up to 20 individuals and due to a largely age-related dominance hierarchy among males, many individuals are prevented from breeding. Adult plumage is not attained until the fourth year, but males can produce motile sperm in their first year. Plasma levels of LH and T peaked just prior to egg-laying among breeding males, but DHT levels remained steady or declined slightly during the breeding period. Adults (greater than 3.5 years) had significantly higher levels of both LH and androgens than did subadults (less than 3.5 years) during the breeding season. Nonbreeding adults had similar levels to those found among the breeding adults, but breeding subadults had higher levels of both LH and androgens than the nonbreeding subadults. These results are interpreted in terms of the opportunities for each of these classes to obtain copulations and are discussed in relation to age-related hormonal secretion in other species. PMID- 1879672 TI - The loss of 45Ca2+ associated with prolactin release from the tilapia (Oreochromis mossambicus) rostral pars distalis. AB - The relationship between tritium 3H-labeled prolactin (PRL) release and the loss of tissue-associated 45Ca2+ was examined in the tilapia rostral pars distalis (RPD) using perifusion incubation under conditions which inhibit or stimulate PRL release. Depolarizing [K+] (56 mM) and hyposmotic medium (280 mOsmolal) increased both the release of [3H]PRL and the loss of 45Ca2+. The responses to high [K+] were faster and shorter in duration than those produced by reduced osmotic pressure. The depletion of Ca2+ from the incubation medium with 2 mM EGTA suppressed the [3H]PRL response evoked by high [K+] or reduced osmotic pressure. Exposing the tissues to Ca(2+)-depleted medium in the absence of high [K+] or reduced osmotic pressure produced a sharp, but brief, increase in 45Ca2+ loss. Cobalt (10(-3) M), a competitive inhibitor of calcium-mediated processes, inhibited the [3H]PRL response to hyposmotic medium and to high [K+]. Cobalt also diminished the increased loss of 45Ca2+ evoked by exposure to reduced osmotic pressure, but was ineffective in altering responses to high [K+]. Methoxyverapamil (D600; 10(-5) M), a blocker of certain voltage-sensitive Ca2+ channels, did not alter either the [3H]PRL or the 45Ca2+ responses to high [K+] and reduced osmotic pressure. Taken together with our earlier studies, the present findings suggest that exposure to high [K+] or hyposmotic medium produces rapid changes in the Ca2+ metabolism of the tilapia RPD that are linked to the stimulation of PRL secretion. Nevertheless, the increased 45Ca2+ loss, but not [3H]PRL release, upon exposure to Ca(2+)-depleted media suggests that Ca2+ loss may not always reflect intracellular events that lead to PRL release. PMID- 1879673 TI - Pituitary and plasma arginine vasotocin levels in teleost fish. AB - The role of arginine vasotocin (AVT) in teleostean osmoregulation is unclear. Its administration may produce dose-dependent effects on renal fluid loss though the physiological significance of such effects is unknown due to the paucity of data on the normal range in pituitary and plasma AVT levels. The present study addresses these questions by examining the pituitary AVT activity in the flounder and plasma AVT concentrations in the flounder, trout, and carp following alterations in environmental tonicity. Flounder pituitary AVT content, measured by bioassay, was elevated in freshwater (FW)-acclimated compared to seawater (SW) acclimated fish and rapidly fell or rose, respectively, following transfer from FW to SW or from SW to FW to attain a new steady state. Plasma levels of AVT were higher in FW than in SW in both flounder and trout and it would, therefore, appear that the synthesis, storage, and secretion of AVT may be enhanced in FW. In the stenohaline carp plasma levels of AVT were unchanged on acclimation from FW to 40% SW. In SW flounder there was a significant positive correlation between plasma osmolality and plasma AVT concentration. Such a relationship was not apparent in FW fish, which may reflect differing roles for the hormone in these two extremes of osmotic environment. PMID- 1879674 TI - The development of a noncompetitive enzyme-linked immunosorbent assay for oncorhynchid growth hormone using monoclonal antibodies. AB - The development of a sensitive and specific two-site, or sandwich, noncompetitive enzyme-linked immunosorbent assay (ELISA) for oncorhynchid growth hormone (GH) using monoclonal antibodies (MCAs) is reported. The MCAs were generated by the fusion of myeloma cells with spleen cells from mice that had been immunized with chum salmon (Oncorhynchus keta) recombinant GH. The MCAs specifically recognized the GH-secreting acidophils in the proximal pars distalis of immature male rainbow trout (Oncorhynchus mykiss) pituitaries. Affinity chromatography using one of the MCAs isolated a single protein with a molecular weight of 22,500 from a rainbow trout pituitary extract. The ELISA recognized recombinant chum salmon GH and the affinity-purified protein but did not recognize chum salmon prolactin, gonadotropin I or II, nor several mammalian hormone preparations. The ELISA recognized GH in rainbow trout, coho salmon (Oncorhynchus kisutch), and chinook salmon (Oncorhynchus tshawytscha) pituitary extracts, but not in goldfish (Carassius auratus) extracts, and recognized GH in rainbow trout, coho salmon, lake sturgeon (Acipenser fulvescens), and bowfin (Amia calva) plasma, but not in goldfish, yellow bullhead (Ictalurus natalis), or lamprey (Petromyzon marinus) plasma. The sensitivity of the ELISA was less than 1.56 ng/ml and circulating levels of GH in the plasma of coho salmon and rainbow trout plasma were measured as 75 and 35 ng equivalents/ml, respectively. PMID- 1879675 TI - Development and validation of a highly sensitive radioimmunoassay for chinook salmon (Oncorhynchus tshawytscha) growth hormone. AB - This study describes the development of a highly specific and very sensitive radioimmunoassay for salmonid growth hormone. Antiserum raised against chinook (Oncorhynchus tshawytscha) GH2, which did not recognize 125I-sPRL and 125I-sGTH (at 1:1000 initial dilution), was able to inhibit growth when injected into rainbow trout (Oncorhynchus mykiss). 125I-sGH2, used as tracer, was not recognized by anti-sGTH or by anti-sPRL. Mammalian GH and ACTH and salmonid GTH, TSH, and PRL did not cross-react in the sGH assay. The inhibition curves for pituitary extracts and plasma from salmonids were parallel to the salmon GH standard, whereas those from carp, tilapia, and catfish showed no significant cross reactivity. The RIA ED90 and ED50 values were 0.2 and 1.5 ng/ml, respectively. Using this RIA for measuring GH release by cultured pituitary cell we observed a strong inhibiting effect of SRIF (10(-6) M) and a stimulatory effect of hGRF (10(-6) M). This RIA allowed us also to detect daily fluctuations in the plasma GH concentration in cannulated rainbow trout. PMID- 1879676 TI - The effect of starvation on growth and plasma growth hormone concentrations of rainbow trout, Oncorhynchus mykiss. AB - Two experiments, one using 0+ the other 1+ rainbow trout, were conducted to investigate the effect of prolonged starvation on plasma growth hormone levels. The results from both experiments were essentially the same. As expected, starvation resulted in cessation of growth and in a lower coefficient of condition, whereas fed fish continued to grow and remained in good condition. Starvation had relatively little effect on the plasma cortisol level; in one experiment levels were elevated temporarily in starved fish, although by the end of the experiment there was no longer any difference between starved and fed fish, and in the other experiment plasma cortisol levels remained very low throughout the course of the experiment in both starved and fed fish. In contrast, in both experiments starvation had a pronounced effect on the plasma growth hormone level, which rose steadily during both experiments, such that it was six times higher after 1 month of starvation in 0+ fish, and five times higher after 6 weeks of starvation in 1+ fish. Thus, paradoxically, fed fish had very low plasma growth hormone levels and grew rapidly, whereas starved fish had elevated plasma growth hormone levels but did not grow. In both experiments a strong negative correlation was observed between the plasma growth hormone level and the coefficient of condition of the fish. The results are discussed with regard to the well-established metabolic changes that occur during starvation, and it is suggested that a major role of growth hormone during starvation is to aid in the mobilisation of fatty acids and glycerol from adipose stores. PMID- 1879677 TI - [Cloning of the Arthrobacter globiformis fcbA gene for dehalogenase and construction of a hybrid pathway of 4-chlorobenzoic acid degradation in Pseudomonas putida]. AB - The Artrobacter globiformis KZT1 fcbA gene responsible for dehalogenase (4 chlorobenzoate-4-hydroxylase) activity was cloned in Escherichia coli and Pseudomonas putida cells. The character of the fcbA gene expression was studied. Notwithstanding amplification of the gene dose and control of the inducible Plac promoter, the level of substrate dehalogenation by recombinant E. coli strains was lower, as compared with that in the original KZT1 strain. Cloning of the fcbA gene in P. putida KZ6R cells utilizing 4HBA resulted in a recombinant pathway of 4CBA degradation, which proved more effective for substrate consumption, in comparison with the original KZT1 strain. PMID- 1879678 TI - [Cloning of the locus encoding synthesis of an outer membrane protein (Omp2) of the calcium dependence plasmid of Yersinia pestis (Lehmann, Neumann)]. AB - The genetic locus of Yersinia pestis encoding synthesis of a 46-kDa heat inducible outer membrane protein (Omp2) was cloned into pBR322 plasmid. The Omp2 was shown to be analogous to previously described YopH and Yop2b proteins. The fifth HindIII fragment of 48-MDa calcium dependence plasmid pCad358 mediates production of 31- and 28-kDa proteins, irrespective of orientation of the insertion. A 31-kDa polypeptide seems to correspond to the YopJ described elsewhere. The maps of BamHI and HindIII of pCad358 region studied differed from those described for pCD1 plasmid of Y. pestis KIM. The products encoded by genes from the fragment cloned in the Pgm+ background give rise to considerable growth of Y. pestis within mouse peritoneal macrophages but were not sufficient to cause lethal infectious process. PMID- 1879679 TI - [Rearrangements of yeast chromosomes revealed by pulsed field gel electrophoresis]. AB - Electrophoretic karyotypes of yeast Saccharomyces cerevisiae integrant strains containing the pYF91 plasmid integrated into the chromosomes I, III, VI, IX, XI were studied. A possibility was demonstrated of visual identification of the chimaeric chromosomes via the molecular weight increase by 13200 bp (the plasmid size) determined by pulsed field gel electrophoresis. Several gamma-rays induced rearrangements of the yeast chimaeric chromosome I causing instability in hybrids were also studied. The deletions induced in the I chromosome were analysed and their size estimated. The technique of pulsed field gel electrophoresis is recommended for determination of insertions and deletions in the chromosomes of yeast Saccharomyces cerevisiae. PMID- 1879680 TI - [Genetic mapping of genes regulating synthesis of acid phosphatases in the yeast Saccharomyces cerevisiae of the Peterhoff yeast collection]. AB - Genetic mapping of yeast genes ACP5, acp83 and ACP82 was performed. According to the results obtained, ACP5 and acp83 are located in the chromosome VI and ACP82- in the chromosome XVI. Based on identity of chromosome location and phenotypes of mutations arising, it was proposed that ACP5 and acp83 are homologous to PHO4 and pho82 genes, respectively, and ACP82--to PHO85 in the yeasts of the same line. PMID- 1879681 TI - [Genetic control of tryptophan hypersynthesis in regulatory mutants of Pseudomonas putida]. AB - The 6-fluorotryptophan resistant MR1 mutant was obtained from Pseudomonas putida M30 (Tyr- Phe-) strain. The mutant was able to excrete tryptophan (60 micrograms/ml) and has derepressed aroF gene encoding 3-deoxy-D arabinoheptulosonate-7-phosphate synthase. The mutation isolated was identified as aroR with the help of cloning early aroF gene of P. putida. On the next step of selection, regulatory mutant MR2 was obtained producing 240 micrograms/ml of tryptophan. The MR2 has derepressed unlinked trpE and trpDC genes and represents a mutant of the trpR type. Expression of the trpE gene of P. putida MR2 weakened in the presence of tryptophan excess in the medium, which points to attenuation of this gene. From the prototrophic variant of P. putida MR2 the MRP3 mutant producing 850 micrograms/ml of tryptophan was obtained. This mutant was characterized by twofold increase in the activity of the anthranilate synthase encoded by the trpE gene. The assay of the activity of tryptophanyl-tRNA synthase in P. putida MRP3 demonstrated that the mutant has TrpS+ phenotype. PMID- 1879682 TI - [Alteration in the content of biogenic amines in two stocks of Drosophila virilis and their hybrids in ontogenesis and under heat stress]. AB - The levels of dopamine and serotonin in two stocks of D. virilis and their F1 hybrids throughout ontogenesis and under heat stress (for 60 min at 32 degrees C) were examined. Sharp increase in dopamine levels was reported under pupariation and with emergence of adults; alterations in serotonin levels were not so obvious. The concentration of dopamine in adults was shown to be considerably higher (more than twice) in the stock 147 than that in the stock 101. Significant increase of dopamine quantity in both stocks was observed under heat stress (serotonin remaining unchanged), while the level of response in the stock 101 was twice as high as in adults of the stock 147. The response typical of the stock 147 was prevailing in the hybrids F1 (147 x 101). PMID- 1879683 TI - [Translocation of chromosome 1/29 and its various phenotypic manifestations in Ala-Tau breed cattle]. AB - 117 heads of Ala-Tau breed cattle were studied cytogenetically. The 1/29 translocation was present in 13 animals of unusual for this breed light-grey colour. Chimerism 2n = 59/2n = 60 was found in twins. Dominant mutation transforming dark brown colour to the light-grey seemed to be present in the 1/29 chromosome locus, near the centromere region. PMID- 1879684 TI - [Genetic polymorphism of the erythrocytic enzymes in the Buryat populations]. AB - Polymorphism of seven erythrocytic enzymes PGM1, ESD, CLO1, PGD and PGP were studied in five samples of Buryats. The main investment into differentiation between populations has been made by the following systems: CLO1, PGD and PGM1. Analysis of genetic distances between populations demonstrated that there was some parallelism among the genetic and anthropological differentiation in the Buryat populations. The groups of the Agingsky county (the area to the east from the Baikal Lake) have probably the largest proportion of the Caucasian genes as compared to other populations studied. One of the characteristics of the Buryats, especially for the population to the east from the Baikal Lake, is high frequency of the PGD allele. The rate of the genetic variability on the intra-population level is higher than the difference between populations. This means that the divergence between the Buryats populations is not very strong. Consideration of the genetic variability on the intra-population level seems to be more perspective for ecogenetic estimation of the adaptive genetic processes than analysis of the differences between populations studied. PMID- 1879685 TI - [Marriage structure of the Kharkov population according to nationality and birthplace]. AB - Positive assortative mating for birthplace and nationality has been revealed by means of sample analysis of couples married in two districts of Kharkov in 1960 and 1985. The contingency coefficient measuring the association between birth places of husband and wife was K = 0.15 in one district in 1960 and K = 0.18 in the other, these values being K = 0.16 and K = 0.18 for these districts, respectively, in 1985. A higher degree of assortative mating was observed for the nationality character: K = 0.40 and K = 0.21 in 1960 and K = 0.23 and K = 0.25 in 1985. The mean marriage substance increased from 578 to 699 km for 25 years. PMID- 1879686 TI - [Serological study of BoLA class I antigens]. AB - Typing reagents were prepared determining the class I antigens of the main histocompatibility complex in cattle (BoLA). The microcytotoxic test was applied to analyse 450 sera (reagents) obtained from cows postpartum. Testing these sera on the panel of lymphocytes from unrelated animals and calculating mutual correlations of the reactions, we determined 113 groups of similarly reacting sera (clusters) which determine 13 specificities of Class I BoLA complex. The majority of these correspond to the internationally approved BoLA antigens. PMID- 1879687 TI - Characteristic features of the sonicated DNA of Agama agama agama L. (Reptilia, Agamidae) on hydroxyapatite columns, using mouse DNA as a reference. AB - Hydroxyapatite column chromatography has been used to study some properties of the extensively sheared DNA of the Rainbow lizard, Agama agama agama. Reassociation studies show that the genome has a Cot1/2 of 370. Approximately 15% of the genome is highly repetitive in nature. This repetitive fraction is resolved into thermally stable and less stable fractions. The stable fraction has a base composition of 47% GC, higher than the 40.2% GC for the native DNA. This stable fraction is believed to be of recent origin. Chromatography of the total DNA of the lizard with linear gradients of phosphate buffer containing 1 M urea resolves it into two components which were shown by thermal fractionation, also in the presence of 1 M urea, to vary in base composition. This behaviour may be characteristic of reptilian genomes and may be used as a basis for studying the structural organisation of the reptilian genome. PMID- 1879688 TI - Comparative cytogenetic studies in Sus verrucosus, Sus celebensis and Sus scrofa vittatus (Suidae, Mammalia). AB - Chromosome studies on the Javan warty pig (Sus verrucosus), the Sulawesi warty pig (S. celebensis) and a subspecies of the wild boar, S. scrofa vittatus, have revealed diploid chromosome numbers of 38. The morphology and C-band size of chromosome 10 are different in S. verrucosus and the two other species. Both S. verrucosus and S. celebensis have a Y chromosome that is larger than the Y chromosome of domestic and wild S. scrofa, and is submetacentric rather than metacentric. There are differences between all three species in the G-banding pattern of the long arm of the Y chromosome. The presence of 2n = 38 chromosomes in the Javan warty pig and the Sulawesi warty pig provides new strong evidence that the basic chromosome number in the genus Sus is 38. The differences in karyotype between these pigs (chromosome 10 and the Y chromosome) confirm that they are separate species. PMID- 1879689 TI - The karyotype of the middle-African hedgehog Atelerix albiventris Wagner, 1841 and its cytotaxonomical relationships to other Erinaceinae (Insectivora: Erinaceidae). AB - Like other hedgehog species investigated hitherto, also the Middle African species Atelerix albiventris has a diploid number of 48 chromosomes. However, Aethechinus and Atelerix display quite distinct cytogenetic characteristics compared to the hedgehog genera Erinaceus, Hemiechinus and Paraechinus. Individual chromosome structures and reactivities permit the recognition of similarities to the Algerian hedgehog Aethechinus algirus and indicate their close relationship. Nevertheless, the proposal by Corbet (1988) to merge the two taxa into one genus, which is contrary to Robbins and Setzer (1985) remains to be clarified by further investigations. PMID- 1879690 TI - Restriction endonucleases in the study of eukaryotic chromosomes. PMID- 1879691 TI - Functional and structural units in the chromomere. AB - Electron microscopic observations demonstrate the existence of several DNA packing levels in the chromomere. A linear DNA molecule forms a big (chromomere) loop anchored to the chromosomal scaffold. The loop forms a set of smaller loops in the rosette pattern. Packing of the DNA by the histone octamer particles results in nucleosomes and nucleomeres. To establish the possible correspondence between the structural units of a chromomere and the genetical units (genes, exons, introns) in it, we compared the lengths of the units. Statistical analysis of the 315 sequenced genes indicate that the average gene size corresponds to the average length of a rosette loop. It means that a chromomere contains one or more genes. Assuming that exon-intron boundaries cannot bind nucleosomes we constructed DNA-packing models of the 88 genes. They demonstrate that the first (in 77.8 per cent of the genes) and the last (in 52.7 per cent) exons of the genes are too short to bind nucleosomes. Many genes contain long (nucleosome binding) pieces of DNA. Long packed pieces are introns in vertebrates; they are exons in invertebrates and plants. The average size gene contains two nucleomeres. PMID- 1879692 TI - Analysis of the cbhE' plasmid gene from acute disease-causing isolates of Coxiella burnetii. AB - A gene termed cbhE' was cloned from the QpH1 plasmid of Coxiella burnetii. Expression of recombinants containing cbhE' in vitro and in Escherichia coli maxicells, produced an insert-encoded polypeptide of approx. 42 kDa. The CbhE protein was not cleaved when intact maxicells were treated with trypsin. Hybridizations of total DNA isolated from the six strains of C. burnetii indicate that this gene is unique to C. burnetii strains associated with acute disease, i.e., Hamilton[I], Vacca[II], and Rasche[III]. The cbhE' gene was not detected in strains associated with chronic disease (Biotzere[IV] and Corazon[V]) or the Dod[VI] strain. The cbhE' open reading frame (ORF) is 1022 bp in length and is preceded by a predicted promoter/Shine-Dalgarno (SD) region of TCAACT(-35)-N16 TAAAAT(-10)-N14-AGAAGGA (SD) located 10 nucleotides (nt) before the presumed AUG start codon. The ORF ends with a single UAA stop codon and has no apparent Rho factor-independent terminator following it. The cbhE' gene codes for the CbhE protein of 341 amino acid (aa) residues with a deduced Mr of 39,442. CbhE is predominantly hydrophilic with a predicted pI of 4.43. The function of CbhE is unknown. No nt or aa sequences with homology to cbhE' or CbhE, respectively, were found in searches of a number of data bases. PMID- 1879693 TI - An improved transformation vector for the lignin-degrading white rot basidiomycete Phanerochaete chrysosporium. AB - In this study, a lignin peroxidase-encoding gene (LIP) of Phanerochaete chrysosporium was disrupted by inserting into its coding region the kanamycin resistance determinant from Tn903. The resulting recombinant plasmid, pUGLG1: kan, was transformed into P. chrysosporium with the expectation that the disrupted gene might replace the homologous LIP gene in the chromosome. However, the results showed that pUGLG1: kan sequences do not integrate into the chromosome; instead, the plasmid is maintained intact in the transformants in an extrachromosomal state. Our data also show that pUGLG1: kan undergoes replication in P. chrysosporium, is maintained as a circular element, is recoverable from meiotic and mitotic progeny, although at a low frequency, and can be recovered intact by Escherichia coli transformation. These results suggest that the GLG1 component of pUGLG1: kan contains as yet unidentified sequences that allow its autonomous replication in P. chrysosporium transformants. PMID- 1879694 TI - M13plex vectors for multiplex DNA sequencing. PMID- 1879695 TI - Sequence of the phosphomannose isomerase-encoding gene of Salmonella typhimurium. AB - The pmi gene, encoding phosphomannose isomerase, of Salmonella typhimurium, was cloned in Escherichia coli K-12, and the protein product visualised in minicells. The cloned gene was sequenced; there was 77.4% nucleotide homology between the cloned pmi gene and the analogous manA gene of E. coli K-12, and 86.2% amino acid sequence homology between their presumptive gene products. PMID- 1879696 TI - Participation of the histone-like protein HU and of IHF in minichromosomal maintenance in Escherichia coli. AB - The closely related Escherichia coli genes, hupA, hupB, himA and himD (hip), encode the bacterial histone-like protein subunits, HU-2, HU-1, IHF chi and IHF beta, respectively. We report here that E. coli minichromosomes [plasmids (2.7 12.2 kb) with oriC] carrying the intact mioC region were unable to transform mutants deficient in both HU and integration host factor (IHF), whereas they could transform mutants deficient in either HU or IHF as efficiently as the wild type strain. Minichromosomes carrying a deletion of the proximal part of mioC or a DnaA box just upstream from mioC could not transform cells deficient in IHF, but could transform cells deficient in HU. These results suggested that HU and IHF participate in minichromosomal replication from oriC in E. coli. PMID- 1879697 TI - Characterization of an Escherichia coli gene encoding betaine aldehyde dehydrogenase (BADH): structural similarity to mammalian ALDHs and a plant BADH. AB - An open reading frame of 1476 nucleotides, cloned from a region of the Escherichia coli genome encoding betaine biosynthesis functions, was shown to encode a betaine aldehyde dehydrogenase (BADH; EC 1.2.1.8). Either of two adjacent codons (5'-GTGATG) could function as a start codon, producing a presumptive polypeptide of 491 or 490 amino acids. The deduced primary structure of the E. coli BADH showed 39-43% positional identity, over its entire length, to aldehyde dehydrogenases (ALDH: EC 1.2.1.3) of mammalian origin. This similarity increased to 75-77% when conservative aa substitutions were also taken into consideration. Spinach BADH was also similar to the bacterial BADH, showing 38% identity and 80% overall similarity. Other homologs included a fungal and a putative bacterial ALDH. Although E. coli BADH was specific for the substrate, betaine aldehyde, it showed the highest levels of similarity to the prototype human ALDH-2. Only one gap in each sequence had to be introduced for optimal alignment. The conservation between E. coli BADH and the ALDHs was also evident in the predicted secondary structures and hydrophilicity profiles of the polypeptides, suggesting a similarity in the overall folding patterns of ALDH and BADH. These observations suggest a common ancestry for BADH and ALDH, preceding prokaryote-eukaryote divergence. PMID- 1879698 TI - Vectors for inserting selectable markers in vector arms and human DNA inserts of yeast artificial chromosomes (YACs). AB - To facilitate studies of gene expression and homologous recombination, plasmids have been developed which permit the insertion of neomycin resistance-encoding gene (NmR) into either the human DNA insert or the vector arm of a yeast artificial chromosome (YAC). To integrate into the YAC arm, the plasmid pRV1 contains a LYS2 (encoding alpha-aminoadipate reductase) gene for selection in the yeast host, and a NmR gene for subsequent selection after transfection of mammalian cells. These two sequences are bracketed by fragments of the URA3 gene (encoding orotidine-5'-phosphate decarboxylase) that can disrupt the URA3 gene in the YAC arm by homologous recombination in yeast. To integrate a selectable marker into the insert, the plasmid pRV2 contains a NmR gene and an intact copy of the URA3 gene, bracketed by segments of an L1 (LINEs) repetitive element. In this case, the vector has been designed for use with YACs that have already been fitted in the vector arm with a different marker (i.e., TK) that has disrupted the URA3 gene in the vector arm. Selection is for the restoration of URA3 gene activity attendant on recombination into an L1 element in the YAC insert. Use of the vectors is illustrated with a YAC clone containing ribosomal DNA. PMID- 1879699 TI - Cloning and structure of the mono- and diacylglycerol lipase-encoding gene from Penicillium camembertii U-150. AB - A gene (mdlA) encoding mono- and diacylglycerol lipase (MDGL) from Penicillium camembertii U-150 has been cloned using a 0.9-kb DNA fragment, generated by mixed oligodeoxyribonucleotide (oligo)-primed polymerase chain reaction (PCR), as a probe. Comparison of the nucleotide sequence of the gene and its cDNA clone, obtained by PCR, revealed the presence of two short introns (56 and 53 bp). Two transcription start points (tsp) were localized by primer extension analysis at 37 and 30 bp upstream from the ATG start codon and were preceded by the canonical TATAAA and CAAT sequences. The deduced amino acid (aa) sequence corresponds to 305 aa including a putative signal peptide of 26 aa. Despite significant differences in substrate specificity, the primary structure of the mature region shows homology (29% and 40%) to the triacylglycerol lipases from Mucor miehei and Humicola lanuginosa. Furthermore, the three residues presumed to form the catalytic site, serine, aspartic acid and histidine, are conserved. Primary structure comparisons of MDGL and triacylglycerol lipases are shown. PMID- 1879700 TI - A marker-coupled method for site-directed mutagenesis. AB - A marker-coupled method for site-directed mutagenesis (SDM) has been developed. In this method, target DNA is first cloned into a plasmid vector which carries an inactivated tetracycline-resistance (TcR)-encoding tet gene. Using this cloned plasmid as template, polymerase chain reaction (PCR) is performed with a mutagenic primer and a marker primer. The mutagenic primer contains the desired mutations to be introduced into the target DNA, and the marker primer contains a mutation for restoring the activity of the inactivated tet gene. The PCR product is annealed with a gapped duplex plasmid template, extended and ligated in vitro. The resulting uni-strand-mutated plasmid is converted into the gapped duplex form, transformed into Escherichia coli JM109 and spread on yeast extract/tryptone culture medium + Tc plates. The TcR colonies grown on these plates all carry active tet genes. Due to the 'tight coupling' between the marker primer and the mutagenic primer formed in the PCR product, these TcR colonies should also carry the mutagenic primer, e.g., the desired mutations in the target DNA. In fact, practically all of the TcR colonies have been found to be the desired mutants in the present experiments. Therefore, this method provides a very efficient approach for SDM. PMID- 1879701 TI - A procedure for amino acid sequencing in internal regions of proteins. AB - We describe a novel procedure for determining the amino acid (aa) sequence of the internal regions of proteins. This procedure has been implemented by directly determining the sequence of aa 65-75 of the product of the trpR gene of Escherichia coli, the trp repressor. This method is based on the insertion of the cleavage site of a specific protease (factor Xa) into the protein immediately before the region to be sequenced by Edman degradation. The simplicity of the procedure makes it appealing for studies of protein structure-function relationships, and of the expression of genetic information. The method is particularly useful when there is ambiguity concerning the co-linearity of the aa and nucleotide sequences. PMID- 1879702 TI - Cys184 and Cys187 of NifL protein of Klebsiella pneumoniae are not absolutely required for inhibition of NifA activity. AB - The sequence Cys184-Ala-Asp-Cys187 in the NifL protein of Klebsiella pneumoniae, for which a role in oxygen sensing and/or metal binding has been proposed, was altered by introducing two mutations, Cys184----Ala and Cys187----Ala, using oligodeoxyribonucleotide-directed mutagenesis. Neither mutation abolished ammonium or oxygen control of nif transcription, although some impairment of function was apparent. The two Cys residues are therefore unlikely to have a direct role in oxygen sensing or metal binding, but probably make some contribution to protein folding or stability. PMID- 1879703 TI - Sequence of gene choB encoding cholesterol oxidase of Brevibacterium sterolicum: comparison with choA of streptomyces sp. SA-COO. AB - The nucleotide (nt) sequence of the cholesterol oxidase (Cho)-encoding gene (choB) cloned from Brevibacterium sterolicum ATCC21387 was determined. The sequence contained an open reading frame with a G + C content of 64.9 mol% that would encode a protein of 552 amino acids (aa). Comparison of the nt sequence of choB and deduced aa sequence to those of the Cho-encoding gene (choA) of Streptomyces sp. strain SA-COO showed identities of 64% and 58%, respectively. N terminal aa sequence analysis of the extracellular enzyme of B. sterolicum confirmed that the mature enzyme consisted of 507 aa with a predicted Mr of 54,902, and was preceded by a 45-aa signal sequence. PMID- 1879704 TI - A thiostrepton-inducible expression vector for use in Streptomyces spp. AB - A shuttle expression vector containing the thiostrepton-inducible Streptomyces lividans promoter, ptipA, and the origin of transfer from plasmid RP4 was constructed. Cassettes containing a promoterless xylE gene upstream from a hyg gene were used to demonstrate thiostrepton-inducible expression from ptipA in both S. lividans and Streptomyces ambofaciens, ptipA was estimated to be induced 60-fold or more in Streptomyces ambofaciens. PMID- 1879705 TI - Regulating the behavior of nursing homes through positive incentives: an analysis of Illinois' Quality Incentive Program (QUIP). AB - The Illinois Quality Incentive Program (QUIP) offers nursing homes a separate bonus payment per Medicaid day for achievement of each of 6 quality standards. Using data from 809 participating nursing homes between 1985-1988, this study found that over 90% of eligible facilities chose to participate annually. Success in achieving bonus payments in multiple standards increased over time, with 27% qualifying for 5 or 6 components by 1988. But the validity of the individual measures and the relationship between achievement of QUIP standards and resident quality was not firmly established. The resident satisfaction standard proved insensitive, with 92% of participating facilities qualifying on this standard. PMID- 1879706 TI - Agents of nursing home quality of care: ombudsmen and staff ratios revisited. AB - Many gerontologists have proposed that ombudsman programs and other forms of community presence should improve nursing home quality of care. This study compared these programs' effects on quality of nursing care on a random sample of 134 Medicare/Medicaid-certified long-term care facilities in Missouri. The presence of an ombudsman program was found to be the most important factor associated with quality for intermediate-care facilities, and it was significantly associated with quality for skilled nursing homes where there was ample staffing of registered nurses. PMID- 1879707 TI - Assessing nursing assistants' knowledge of behavioral approaches to mental health problems. AB - Nurse's aides are the primary caregivers in nursing homes, a major receiving site for elders with behavioral and psychiatric problems. We describe the development, psychometric properties, and utility of a brief instrument designed to assess aides' knowledge of three specific mental health problems (depression, agitation, and disorientation) and behavioral approaches to them. The instrument was administered to 191 nurse's aides and 21 clinicians with training in behavioral management and experience with older residents. The nurse's aides averaged 11 of 17 correct answers, and the clinicians averaged 15 of 17 correct answers. Implications for staff training and consultation activities in nursing homes are discussed. PMID- 1879708 TI - Senior centers and minority elders: a critical review. AB - This paper examines the literature on senior center participation and factors related to participation for minority elders. The extent of involvement of minority elders in senior centers is unclear due to lack of data for certain groups and methodological problems in some studies. Traditional and emerging factors that might affect minority elderly's senior center participation are identified and discussed. Suggestions are provided for expanding the knowledge base in this area. PMID- 1879709 TI - Family and community: changing roles in an aging society. AB - A holistic approach to the provision of social care of the elderly can best meet their future needs for assistance. In this paper, the concept of social care is delineated, and a systemwide model presented. This model emphasizes the interrelatedness of the component parts--informal, mediating, and formal--and the need for well-articulated linkages among them. Trends affecting future demand for care, and the ability of family and community to respond, are discussed. Although the family will retain an important role, some of its functions may shift to formal care in the decades ahead. Within the proposed framework, a research and policy agenda is suggested. PMID- 1879710 TI - Unfit survivors: exercise as a resource for aging women. AB - Some researchers have suggested that about 50% of aging decline is preventable through improved life-style habits such as participation in regular exercise, yet exercise as a resource for healthier survival is being ignored by many aging women. Though recent research findings highlight regular physical activity as a potent factor in combatting hypokinesis (the disease of inactivity), numerous real and perceived barriers to exercise stand between the older woman and her ability to achieve a better quality of life. Among strategies that have been developed to overcome these barriers are social empowerment initiatives that may encourage women to combat disability by engaging in regular exercise. PMID- 1879711 TI - Eliciting medical care preferences from nursing home residents. AB - We interviewed 44 residents of a nursing home to assess their preferences for care. Using case vignettes, we asked residents about resuscitation, hospital transfer, feeding tubes, and restraint use. Most were opposed to aggressive care unless the purpose was to enhance comfort or safety. However, sufficient diversity of opinions points to the need for advanced directives. PMID- 1879712 TI - Factors affecting decisions to institutionalize demented elderly. AB - This study followed 321 community-based patients with documented dementias, 22% of whom were institutionalized after 1 year. Multivariate analyses indicated that none of the patient characteristics, such as level of cognitive, psychiatric, or neurological impairment, predicted institutionalization. Social psychological characteristics, type and number of caregivers, and subjective caregiver distress did predict which patients were ultimately institutionalized. Implications for treatment planning are discussed. PMID- 1879713 TI - Time spent caregiving and help received by spouses and adult children of brain impaired adults. AB - Caregivers for brain-impaired adults differ in living arrangements, amount of time spent giving care, and assistance received from family and friends and from paid help depending on their kin relationship and employment status. Spousal caregivers devote large amounts of time to caregiving, and husbands spend no less time than wives. Most caregivers receive little assistance from other family members and friends, but husbands receive more than others. Employed spouses receive more paid help than those without jobs, but employment does not affect the amount of paid help received by adult daughters. PMID- 1879714 TI - Information and referral service usage among caregivers for dementia patients. AB - Questionnaires were mailed to 257 callers of a toll-free telephone "helpline" specializing in Alzheimer's disease and related dementing illnesses; 125 (48.6%) were completed and returned. On the average, 3.94 requests for information were made per call. The most common requests concerned services delivered to the home, general information about dementia, information about adult day care, and support group information. Results indicated that a telephone-based information and referral helpline is useful in disseminating knowledge about resources to caregivers of older community-residing adults with cognitive impairment. PMID- 1879715 TI - Relationships between caregiving daughters and their elderly mothers. AB - In this qualitative study of 29 pairs of widowed mothers and their caregiving daughters, we employ social exchange theory to identify three relationship types: intrinsic (45%), ambivalent (34%), and conflicted (21%). These types differ in the extent to which the women receive rewards from interacting with their partner, experience costs in their interaction, handle conflicts that arise in their relationship, and express feelings of concern for each other. They also differ in that daughters in intrinsic pairs have fewer children and shorter caregiving histories than daughters in ambivalent or conflicted pairs. PMID- 1879716 TI - The relationship among negative life events, cognitions, and depression within three generations. AB - This study investigates the extent to which cognitions mediate the relationship between negative life events and depression. College students and their same-sex parents and grandparents (N = 171) completed measures of stressful life events, automatic thoughts, dysfunctional attitudes, and depression. There was an interaction between negative life events and cognition for the young adults but not for either of the older groups. PMID- 1879717 TI - A program of friendly visitors as network builders. AB - The Sunshine Visitors program is an experimental, friendly visitor-type program that trains volunteers to function as network builders with their isolated, elderly visitees, working to strengthen their social support networks. A unique training program was developed and some success with this type of visiting was achieved, particularly with regard to meeting relational needs. The volunteers, though, tended to encourage network building rather than getting directly involved with the client's social network. PMID- 1879718 TI - Mental health services of the rural elderly outreach program. AB - This paper describes an elderly outreach program (EOP) designed to identify and provide mental health services to the rural elderly. The project integrates a variety of health, mental health, and human service agencies in the planning and delivery of services. Five referral sources are identified and described as well as the assessment, treatment, and referral process. Outcomes are discussed in terms of: characteristics of persons served, ability of the project to identify and deliver mental health services, treatment effectiveness, and cost effectiveness of the project. The EOP seems to have prevented an increase in need for mental health care among Iowans that might have occurred in the program's absence. PMID- 1879719 TI - Cognitive-behavioral interventions for treatment of depression in Alzheimer's patients. AB - This paper presents two strategies for treating depression in Alzheimer's patients. Cognitive therapy, used with mildly demented adults, challenges the patient's negative cognitions in order to reduce distortions and enable the patient to generate more adaptive ways of viewing specific situations and events. Behavioral intervention, used with more moderately or severely demented adults, attempts to modify person-environment interactions by increasing the level of positive activities and decreasing negative ones (Lewinsohn et al., 1984). Both theories have been used successfully in clinical settings. PMID- 1879720 TI - Vision ignored in study of falls. PMID- 1879721 TI - [Cryosurgery of the uterine cervix. Our experience in 3,184 cases]. AB - An analysis is made of 3,184 cases of cryosurgery of the uterine cervix treated along 18 years for diverse types of lesions: 2,050 cases of ectropion of the cervix (64.38%), 811 chronic cervicitis (25.47%), 48 eversions of the cervical canal (1.51%), 24 of cervical condyloma acuminata (0.75%) and 251 of CIN (7.88%). A nitrous oxide cryosurgical system was used. This study evaluate the features of the cryolesion, correlating the freeze time, the size of the frosted area around the probe, the size of the resulting ice-ball and the depth of the epithelial tissue necrosis microscopically measured. For this study cryosurgery was applied to the cervix of 56 women, 1 to 7 days before hysterectomy was performed for benign disease. Statistical analysis was made using regression-correlation calculations to determine the correlation coefficient (r), concluding that the freezing effect and the depth of tissue necrosis are not correlated with the freeze time, but it was demonstrated that there is a reliable correlation between the width of the frosted area around the probe and the depth of tissue necrosis. The extension of cryolesion was influenced by the type of probe, the anatomical position in the cervix, shape of the external is and freeze time, which may be related with the pressure of the gas and the possible clogging of the tubes by pollution. In this paper it is studied too the histopathologic features of the cryolesion. The results obtained in the diverse groups of treated lesions were: 1. In 92% of cases of mucous ectropion of the cervix, one treatment was enough to heal the lesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879722 TI - [Postnatal transmission of the human immunodeficiency virus (HIV). History of brief breast-feeding. (Presentation of a clinical case)]. AB - We studied a case of a woman without previous risks of HIV infection. This woman was transfused for obstetric reasons in April, 1986. Two units of blood were provided by paid donors. The newborn was breastfed for only two weeks. After twelve months symptoms of HIV showed up. Resembling symptoms appeared in the daughter 36 months later breastfed. Both were classified as having AIDS 3 years after the birth. The husband remains negative ten months after his last sexual contact. In conclusion, vertical transmission of HIV through breastfeeding is possible and perhaps should be more closely evaluated. PMID- 1879723 TI - [Post-menopausal osteoporosis in Mexico]. AB - A review of general aspects of osteoporosis and of the post-menopausal type specially; clinical appearance and hormonal mechanisms are briefly reviewed. Special emphasis is made upon sexual hormonal events. Demographic, socio-economic and epidemiological changes in Mexico, are analyzed; explaining their causes, present status of the problem and its possible future projection. Finally, several propositions are made in order to face the problem, as follows: 1) Promotion for more research studies as to incidence, risk factors, determination of population standards for bone mass, 2) Health education programs, and 3) Prevention and treatment programs. PMID- 1879724 TI - [Gestational trophoblastic disease. Prevalence and epidemiologic features at the IMSS Torreon Medical Center]. AB - From August 1st, 1987, to August 31 1989, there were 18 patients with trophoblastic gestational disease (TGD). In that time there 12,263 births for a frequency of TGD of 1:681, the prevalence was 14.6 X 10,000 births. The most frequent symptom was nausea and the most frequent sign, abnormal uterine bleeding; uterine growth not accord to gestational age was not a constant sign. Ultrasound was the method of diagnosis and in all of the cases there were confirmation of diagnosis by tissue exam. The follow-up of the patients was done by standard protocol; oral contraceptives were used for family planning. Our findings are discussed and compared with those in the literature. PMID- 1879725 TI - [Importance of free intracellular calcium in the physiopathology of pre eclampsia]. AB - Due to the participation of intracellular free calcium in the mechanisms of vascular smooth muscle contraction, and its importance in the physiopathology of essential arterial hypertension, its possible role in pre-eclampsia physiopathology, was investigated as a cellular model, platelets, were use, as they are similar to vascular smooth muscle cells. The study purpose was to investigate if intracellular concentration of ionized calcium is greater in the patients with pre-eclampsia than in normotensive pregnant women, and also, if there exists a correlation between intracellular calcium concentrations and arterial tension, Seven pre-eclamptic patients, diagnosed by the following criteria: arterial tension greater than or equal to 130/90 mmHg, edema and proteinuria, between 20 to 35 years of age, during the third trimester of gestation, without personal nor family antecedents of hypertension; none of them received treatment at the time, were studied. As control group seven normotensive pregnant women, equal by chronologic and gestational age, were included. Intracellular calcium in platelets was measured by Fluo-3-Am, and arterial blood pressure with conventional sphygmomanometer. Intracellular calcium and arterial blood pressure values, were compared, in both groups by Student's t, and analysis of lineal regression between intracellular calcium and mean arterial blood pressure, was done. Intracellular calcium was significantly greater in patients with pre-eclampsia, than the ones in the control group (142 +/- 5.6 vs 110 +/- 14 p less than 0.0001). Mean arterial blood pressure was also significantly greater in patients with pre-eclampsia (114 +/- 5 vs 83 +/- 3 p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879726 TI - [Potentiation of vascular responses induced by placental water-soluble factors of women with pregnancy toxemia]. AB - This study shows an experimental model in vitro useful to evaluate vasoactivity of EHP. The findings are consistent with other author's reports, as to the potentiation capacity of different vascular responses with biologic fluids in women with EHAE. As far as we know, this is the first report mentioning the placenta as the origin site of this type of substances. PMID- 1879727 TI - [Multifactorial analysis of patients with endometriosis in an institutional program of assisted reproduction]. AB - It is a retrospective and transverse study with an analysis of results from patients submitted to intrauterine insemination (IIU), intratubal gamete transfer (GIFT) and in vitro fertilization and embryo transfer (FIVTE), at the Clinic of Assisted Reproduction, Instituto Nacional de Perinatologia in Mexico City. From 134 cycles of patients submitted to IIU, 113 corresponded to women with diagnosis of sterility from non determined cause, and 21 to cases with endometriosis, and at least one permeable tube. From the first group, 22 pregnancies were obtained, for a monthly fertility rate of 19.4%; and from the second one, 12 pregnancies with a fertility rate of 56%. This, which is very high , may be explained by the relatively small number of cases in the second group, or else, by the influence of a previous medical treatment for endometriosis; the square Chi analysis shows a P less than 0.01 in the two groups. In the GIFT and FIVTE cases, from which 35 cycles were analyzed, per each procedure, there were 10 pregnancies, 9 for GIFT and one for FIVTE; the amount is very limited in order to obtain conclusions, but it seems that there is a proportional tendency in GIFT to less amount of pregnancies in women with endometriosis. The analysis of hormonal follow up did not show differences in the groups, and the averages may be useful to determine, early, the cancellation, or not, of an stimulation cycle. Finally, in FIVTE cases there is a diminution of fertilization index in women with endometriosis (53%), as compared with the cases without disease (80%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879728 TI - [The mouse test. Correlation between the segmentation of murine embryos and the fertilization and segmentation of human ovocytes and pre-embryos]. AB - The "mouse test" resulted to be an indispensable requisite in order to do, with security, although not complete, the serum selection, to use in the extracorporal phase of FIVTE. Because of the observations it is considered that it should be tried to addition the culture medium with good quality sera; which is evident with a 90% rate, or more, of segmentation in the embryonic system of mouse, of two cells. PMID- 1879729 TI - [Ultrastructural identification of human immunodeficiency virus in placenta, embryonic tissue and semen]. AB - The objective of this paper was to evaluate, ultrastructurally the placental site, placenta, umbilical cord, embryonal tissues, and semen from 10 patients (5 females and 5 males), seropositive for the Human Immunodeficiency Virus. The tissue samples were processed by the routine techniques for electronic microscopy, and were examined with a Zeiss EM-10C Electronic, transmission microscope. Among the decidual cells of the placental site, macrophages were found, which contained vacuoles with particles similar to a virus, inside. Similar to virus, particles were found among microvilli of syncytiotrophoblast; it presented with a thick basal membrane and with calcifications. Hyperplasia of Hofbauer cells was seen, although there were not viral particles inside. In the membrane of fetal erythrocytes there particles, electron dense, possibly from viral origin. Viral particles were identified in the nuclei of endothelial cells of the brain and lung. In the semen budding areas were seen in immature spermatozoon; and similar particles were seen y spermatozoa, probable desquamation cells, and in seminal protein, in free form. It is concluded that the HIV may be transmitted via transplacental in very early stages of gestation. The hyperplasia of Hofbauer cells can be a response of local defense. And finally, the presence of viral particles in the different components of semen favor its transmission by sexual contact. PMID- 1879730 TI - [Synergistic reactions in the normal state and after exposure to vibration (data of the electromyographic studies)]. PMID- 1879731 TI - [Hygienic significance of noise level in the development of diseases with temporary disability among petroleum-processing plant workers]. AB - A correlation was established between morbidity with temporary disability among oil-processing plant workers and the levels of the noise dosages received in one working shift. The morbidity rate among the engine-drivers examined was generally higher than that in the group of operators. The correlational analysis of morbidity versus the complex hazard indices revealed that the latters' growth resulted into increasing morbidity rate, but the same correlation was less vivid in case with the workers affected with the smallest noise dosages (up to 1.0). The noise dosage increase (over 4.0) revealed no adequate correlation between morbidity and the complex hazard indices. PMID- 1879732 TI - [Characteristics of the blood lipoprotein spectrum in truck drivers from the rural Northern Caucasus areas]. AB - Studies were performed of the blood lipoprotein spectrum in 20-59-year-old truck drivers working in Northern Caucasus rural areas, depending on the age, duration of work in the profession and nationality, in comparison with male workers of other professions in the same areas. It was established that, in indigenous male workers of other than truck-driver's profession, the average levels of different cholesterol lipoproteids were lower than in other ethnic groups, whereas the hypoalfacholesterolemia occurrence was two-fold. In truck-drivers of both indigenous and non-indigenous groups, the lipoprotein spectrum age-related changes were similar. In the non-indigenous drivers' group, hypercholesterolemia was highly prevalent, and hyperalfacholesterolemia was less prevalent than in other professional groups. Also, IHD cases were more characteristic of the indigenous drivers' group. The data obtained witnessed in favour of a differentiated approach in the planning of preventive activities with due account of the population's ethnic and occupational characteristics. PMID- 1879733 TI - [Activities and tasks of the journal "Gigiena truda i professional'nye zabolevaniia" ("Work hygiene and occupational diseases") in the new economic conditions]. PMID- 1879734 TI - [Hygienic and physiological aspects of evaluation of new types of protective clothing for railroad workers]. AB - In the Soviet rail-road transport system, timely provision of individual protective devices was authorized by a special instruction of the Rail-Roads Transport Ministry. New materials and overalls are being introduced to adapt the individual safety measures to new labour conditions and the new chemical substances used in the rail-road transport system. Hygienic, physiological and laboratory techniques are widely used to assess the properties of new devices. The evaluating techniques and approaches used and improved in the transport industry can be applied to in other branches. PMID- 1879735 TI - [Isolation of antigen-active biopolymers from Candida maltosa culture fluid for obtaining allergens of diagnostic value for examination of industrial microbiology workers]. AB - The membrane filtration technique and column gel chromatography+ (with sepharose 6B or sephacryl S-200) were used to receive fractions of KJ Candida maltosa, strain VSB 899, which were studied with highly effective liquid chromatography, immunochemical reactions and intracutaneous allergotesting on guinea-pigs sensibilized with VSB 899 live cultures. In the whole KJ strain VSB 899 concentrate, 8 components were identified, six of which had molecular masses from 350,000 to 18,000 and had no analogue in the surface antigen preparation (SAP) from the same strain of yeast-like fungi. It was shown that the SAP-related antigen determinants were present in predominantly polysaccharide-containing fractions. In intracutaneous allergotesting, chromatographic fractions with molecular masses of 50,000 and 18,000-35,000 were most manifesting. It was supposed that still further purification of the allergen will increase its specificity. PMID- 1879736 TI - [Synergistic effect of organic solvents and tobacco smoke on the indicators of humoral immunity in humans]. AB - Medical examinations were performed among 49 non-smokers, 47 workers who had been smoking for more than 10 years, 19 non-smokers exposed to organic solvents and 41 smoking persons occupationally exposed to organic solvents. Both cigarette smoking and the action of organic solvents. decreased the levels of IgA, AgG, IgM and that of lysozyme. In persons exposed to the actions of both cigarette smoking and benzol and its homologues, more significant decreases of IgA, AgG, IgM and lysozyme concentrations were revealed as compared to those affected by one of the factors. The same concerned the IgD level. The contributors proposed that cigarette smoking should be taken into account when evaluating the immunotoxic properties of industrial factors. PMID- 1879737 TI - [A method of quantitative analysis of bendiocarb in the air of the work area]. AB - Proposed was a highly sensitive technique for a quantitative assessment of the newly developed insecticide bendiocarb++ in the working zone air (0.1 hg in the given air sample, or 0.025 mg/m3). The technique was tested in toxicological studies of bendiocarb++ contents in the working zone air. PMID- 1879738 TI - [Determining the level of yttrium oxide-coated silicon nitride in the air of the work area]. AB - To measure the concentrations of yttrium-oxide-coated small-dispersed silicon nitride plasma powder, the air was aspirated at the amount of 10-15 litres per min through the AFA-XP filter. The filter was limed in a platinum crucible, the residuum being alloyed with Na2CO3, Na2B4O7, NaNO3 in ratio 10:5:1. The alloy was transferred into solution in which the silicon content was assessed through reactions with ammonium molybdate, and yttrium--through reactions with arsenaso III. The sensibility rate for silicon was at 0.07 mg/m3. PMID- 1879739 TI - [A method of determining the level of luminescence-producing additive (DHTI-150A) to zinc galvanic electrolytes in the air of the work area]. AB - A photocolorimetric technique was proposed for determining the working zone air content of the glitter-additive (DXTU-150) used in galvanic zinc electrolytes. The technique was based on the phenomenon that the additive's particles, after coming into a contact with n-nitro-dyazobenzol, produced coloured chemical products. PMID- 1879740 TI - [Comparative toxic effect of mercury ion (II) as cation and complex anion on the body and cellular levels]. PMID- 1879741 TI - [Results and prospects of scientific cooperation in the field of occupational hygiene between USSR and Finland]. PMID- 1879742 TI - [Characteristics of physiological reactions during work in coal miners with hypertension]. AB - Vegetative equilibrium disorders in hypertensive-diseased miners resulted from pathologic developments in the limbic -reticular structures. Those were characterized by a hyperfunction of the ergotropic nerve formations. The vegetative control reorientations were accompanied by narrowing the amplitude of the homeostatic regulation vegetative reactions and engaging the mechanisms of adaptation. The vegetative state stabilization in the diseased workers was attained through a partial avoiding ot the most labour-intensive forms of activity and choosing more preferable labour operations. But the latter did not entirely exclude the labour conditions which would result into inadequate vegetative reactions. PMID- 1879743 TI - [Predicting the development of vibration disease in coal miners exposed to local vibration combined with noise and dust]. AB - The contributors proposed a differentiated diagnostic technique which included 10 most informative physiologic, anthropometric and biochemical+ indices to provide the most reliable data (95% reliability) on the adaptation and compensatory mechanisms under local vibration and in combination with noise and dust, and with due account of the individual sensitivity to local vibration. Testing of the technique demonstrated its high accuracy in determining the levels of "exhaustion", and of "the normal state" of the adaptation-compensatory mechanisms, and its applicability for vibration disease prognosis in individual++ workers, thus establishing corresponding in preventive medical examinations, occupational selection, preventive measures' planning, and in expert solutions requiring precise diagnostic techniques. PMID- 1879744 TI - [Basic achievements in the diagnosis and in the problems of the pathogenesis and clinical picture of respiratory organ diseases of dust etiology]. AB - The article contains new data concerned with the respiratory pathologic processes caused by industrial aerosols of different compositions, as well as the mechanisms of their functioning and development. Current problems of occupational lung diseases' treatment are considered in this connection. PMID- 1879745 TI - [The dynamics of the psychophysiological indices of occupational fitness in the students of vocational training centers and in underground miners]. AB - The psychophysiological indices of occupational fitness are characterized by stability in the age groups from 17 to 40 with subsequent diminishing. Lesser degrees of emotional stability were found in teenagers in vocational training schools. The professional fitness assessment of vocational school trainees should be performed with due account of the occupation-related intensive changes in sensomotor reactions and coordination. PMID- 1879746 TI - [Differences in morbidity between male and female machinery operators in chemical manufacture]. AB - Statistical analysis of the rate of applying for medical advice, morbidity and the detailed medical examinations' data concerned with chemical industry machine operators, revealed considerably higher respective rates in men as compared with women. It was proposed that the different rates could be accounted for by the men's and women's social role differences, which influenced their functioning and hygienic behaviour in the occupational conditions. PMID- 1879747 TI - [The clinical picture and diagnosis of manganese-induced parkinsonism]. AB - As a result of 5-year-long electromyographic observation of 144 persons engaged in ferroalloy production, the parkinsonism syndrome was diagnosed in 4 persons. The disease development was slow, gradual, with the muscular tension growth against the asthenovegetative symptoms. This particularity did not correspond to the traditional view of the three-stage development of chronic manganese intoxication prior to the acute phase of manganese parkinsonism. The contributors hold that the stretch reflex proved to be the most early-stage oriented, prognostically and diagnostically reliable among the other electromyographic techniques. PMID- 1879748 TI - [The toxicological hygienic evaluation of the manufacture of epoxy resins based on complex glycidyl ethers]. AB - The workers engaged in the processing of the UP-671, UP-671D, UP-677, UP-680 and UP-682 epoxide resins are influenced by both initial and intermediate industrial products, as well as the resins' volatile components in MAC threshold concentrations. The workers engaged in major professions displayed upper respiratory allergic diseases, contact and allergic dermatitis, sensibilization to epichlorhydrine, staphylococci and kidney allergen. Euthyroid goiter was diagnosed in most workers, along with thriiodothyronine decrease in blood serum and a higher rate of chromosomal aberrations in lymphocytes. The experimental studies performed revealed moderate-degree toxicity in the resins, their cumulation properties, as well as allergenic, irritating, mutagenic and embryotoxic characteristics. Basing on the results of the study, the USSR Health Ministry adopted the working zone air MAC for the resins at the level of 0.5 mg/m3, vapours, 2nd degree of hazardousness. PMID- 1879749 TI - [Acute occupational poisonings in enclosed spaces]. AB - The contributors provide an analysis of the conditions and reasons accounting for the acute occupational intoxications in closed environments, which occurred in Moscow in 1986-1989 and resulted in 18 deaths. Proposals are made with regard to a state standard act on the safety rules for working in closed environments with the texts of some paragraphs to this act. PMID- 1879750 TI - [The use of laser therapy in dust-induced bronchitis]. AB - Low-intensive laser was used in the treatment of dust bronchitis with bronchospastic syndrome. As a result, bronchospasms were relieved, the external respiration function improved and corticosteroid preparation dosages were lowered. Stimulation of the immune system was performed through the T-cellular immunity. PMID- 1879751 TI - [A photometric method for measuring the concentration of caustic alkalies in the air]. AB - The article contains a description of a new photometric technique of measuring caustic alkali content in the working zone air. The technique proved to be sensitive in the presence of carbonic acid gas (the lowest degree of measurements at 0.25 mg/m3 in 100 dm3 air sample). PMID- 1879752 TI - [The potentials of the ShVIL-01 device for the integral assessment of variable noise and local vibration]. AB - The article is addressed to a broad range of experts and provides information on the design and serial production of a new device for automated measurements of energy-equivalent variable noise levels in combination with the phonometers produced both in the USSR and abroad. The technical characteristics of the device and description of its use are given, along with the tables of equivalent levels into the share dosage conversion and the conversion of the exposition levels into the share dosage for respective standards and hygienic norms-based values. PMID- 1879753 TI - [Problems in the further development of postgraduate training in industrial sanitary chemistry for the laboratory physicians of epidemiological health stations]. AB - The article narrates on the domain of the sanitary inspection medical laboratory workers' supervision in the field of industrial chemistry and their experience in handling different physical and chemical analysis techniques. It is indicated that sanitary inspection medical laboratory personnel requires constant postgraduate training. Proposed is the respective training programme adopted at the Institute for Postgraduate Training of Physicians, Moscow, which includes samples' selection, physical and chemical analysis testing and application in specific conditions, statistical assessment of the results obtained. The programme also includes the hygienic aspects, e. i. current sanitary control, labour hygiene in different gas discharge-related conditions. Practical training is performed in small groups of 2 or 3 persons, thus facilitating adoption of skills in using various analysis techniques. Initial, current and intermediate control, tests and situational analysis are used in the training process. PMID- 1879754 TI - [The sanitary improvement of the working conditions for workers in the explosive forming of parts by excluding mercury fulminate from the technology]. PMID- 1879755 TI - [The dynamics of the indices of lipid peroxidation and antioxidative activity in prolonged experimental exposure to epoxy compounds]. PMID- 1879756 TI - [The evaluation of the enzymatic oxidation of pyrazolone derivatives in the liver of workers in the aluminum and chemical industries]. PMID- 1879757 TI - [The use of enterosorption in treating experimental lead poisoning]. PMID- 1879758 TI - [Conventions of the International Labor Organization of the UN and the participation of the USSR in their implementation]. PMID- 1879759 TI - [The health status of the crew members of nuclear-powered icebreakers]. AB - Established was the influence of neuroemotional stress on the health state of atomic-powered ice-breaker sailors working in Arctic autonomous navigation. No specific factors (ionizing radiation) were found. PMID- 1879760 TI - [A radiation hygiene assessment of the working conditions of angiography specialists working using image converters and x-ray TV sets]. AB - Ever-growing bulk of medical equipment used in major health centres with consequent increase in the volume of the angiocardiographic procedures performed, result into greater dosages gained by the medical personnel involved. In this connection, the major dosage-forming factors in different professional medical groups were evaluated. The head, hands and feet were defined as "the critical zones" for angiographic unit personnel. The only possible way of protecting hands was proposed--by means of shortening the time of irradiation, e. i. by establishing hygienic standards for angiographic procedures and operations. PMID- 1879761 TI - [The evaluation of the efficacy of preventing cardiovascular diseases in the employees of central institutions]. AB - Assessment was made of the health state of the administrative personnel in a ministry, with an analysis of morbidity based on the data of a year-long outpatient observation of the ministerial officers. Instrumental techniques were used in CVS examinations, and the current health improvement measures, with due account of their effectiveness and performance, were taken into consideration. Substantiated was the applicability of the hemodynamic indices as a criterion of the effectiveness of primary and secondary prophylaxis of cardiovascular diseases. PMID- 1879762 TI - [Evaluating parachute-drop stress by measuring blood lipids]. AB - An attempt to evaluate parachute-drop related stress by determining the blood lipid profile (cholesterol, LDL, HDL, apo-A, apo-B, and triglycerides) is reported. Measurements were made on starting the parachute course, just before the first jump, and just after the third jump. On these 3 occasions 38 combat troops answered psychological questionnaires and 30 of them gave blood samples. While there were significant fluctuations in level of all blood lipids and their apoproteins, they could not be correlated selectively with presumed levels of stress. The well-known difficulties in field studies in controlling crucial factors such as the exact timing of the measurements and food intake (specific diet or fasting) make questionable the use of biochemical markers in measuring stress under the conditions of our study. It is possible that the high rate of refusal to give blood samples biased the findings. PMID- 1879763 TI - [Procurement of corneas for transplantation]. AB - We prospectively studied all deaths in this hospital from July 1, 1989 through December 31, 1989 for possible eye donations. During this period 539 patients died, of whom, 219 were suitable candidates for donation, and 61 donations were obtained (11.3%). In the course of the study the procurement rate increased progressively as a result of a higher level of effort and awareness by the medical staff. PMID- 1879764 TI - [Early vs delayed cholecystectomy for acute cholecystitis]. AB - The timing of cholecystectomy in acute cholecystitis is still controversial. A marked change toward early surgery has been noted in the past decade. In a retrospective study of 197 patients we evaluated the results of cholecystectomy in 117 who underwent elective cholecystectomy, and in 80 operated on during the acute phase of cholecystitis. The diagnosis of acute cholecystitis was by isotope scan (HIDA) or ultrasound. There was no case of misdiagnosis. 3 patients died postoperatively: 2 in the early operation group (1 had emergency cholecystectomy) and 1 in the elective group. Postoperative complications were more frequent in the early surgery group (p = 0.06). The highest morbidity was in early cholecystectomy in those older than 60 years who had cardiovascular disease (p less than 0.0002). Hernia in the scar was a unique complication of the early operation. According to most studies reviewed, early operation eliminates the need for emergency operation when conservative treatment fails, without increasing morbidity or mortality. Therefore, early operation during the acute phase of cholecystectomy is advised. For patients older than 60 years who have cardiovascular disease, we recommend delaying surgery until the acute inflammation subsides. The waiting period before surgery should be as short as possible in order to reduce the risk of recurrent cholecystitis and its complications. PMID- 1879765 TI - [Sedural toxicity]. AB - Phenazopyridine (Sedural) is widely used in the treatment of dysuria. It is considered a benign drug and most physicians are unaware of its potential toxicity. A 24-year-old woman who developed methemoglobinemia, acute renal failure and hemolytic anemia following a single 1 g dose of the drug is presented. PMID- 1879766 TI - [Acute hypertrophic gastropathy of childhood]. AB - Acute hypertrophic gastropathy of childhood is a rare disease characterized by gastrointestinal complaints and hypoalbuminemia due to protein loss from the stomach. The disease is benign, with complete recovery within a few months. We describe 2 girls with this condition, both 3 years old, in whom a detailed workup was performed, including upper gastrointestinal tract X-rays, ultrasound examination of the abdomen, and gastroscopy with mucosal biopsy. Gastrointestinal protein loss was demonstrated by measuring alpha 1 antitrypsin in the feces. Both children recovered spontaneously within a few weeks. PMID- 1879767 TI - [Spontaneous chylothorax in the neonate]. AB - Chylothorax is a rare cause of respiratory distress in the newborn and is the most frequent type of neonatal pleural effusion. We report 3 cases of spontaneous chylothorax in neonates, 2 boys and 1 girl, all of whom suffered from respiratory distress and required intensive care, including repeated thoracocentesis and mechanical ventilation. Anticipation and prompt recognition of this neonatal emergency and appropriate therapy are essential to ensure its generally favorable prognosis. PMID- 1879768 TI - [Diagnosis and treatment of Hirschsprung's disease in adolescence]. AB - Hirschsprung's disease is the most frequent cause of large intestinal obstruction in the neonatal period, during which the majority of cases are diagnosed. In about 5 of cases diagnosis is not established until adolescence. We present a 12 year-old boy with Hirschsprung's disease, treated since childhood for constipation. Early diagnosis avoids complications. PMID- 1879769 TI - [Scurvy from self-imposed diet]. AB - Scurvy, a rare disease, is still found today in malnourished patients. We recently diagnosed a case of scurvy in a 64-year-old woman resulting from a self imposed diet. She had severe anemia and the characteristic gingival and skin lesions, which responded dramatically to ascorbic acid therapy. We report this case to make physicians aware of the possibility of scurvy and of its clinical symptoms. PMID- 1879770 TI - [Kidney biopsy in systemic lupus erythematosus]. PMID- 1879771 TI - [Thirty years of methotrexate treatment for psoriasis]. PMID- 1879772 TI - [Pancreatic carcinoma, sex hormones receptors and treatment with tamoxifen]. PMID- 1879773 TI - [Significance and management of non-Q wave myocardial infarction]. PMID- 1879774 TI - [Congestive heart failure: some mechanisms and therapeutic implications]. PMID- 1879775 TI - [Mollaret's syndrome: recurrent benign aseptic meningitis]. PMID- 1879776 TI - [Pulmonary artery rupture from the Swan-Ganz catheter: incidence, pathophysiology, treatment, prevention]. PMID- 1879777 TI - [New outlook on the mechanism of fluoride action in preventing caries]. PMID- 1879778 TI - [Palpitation]. PMID- 1879779 TI - [Pediatric AIDS: a special medical challenge]. PMID- 1879780 TI - [Neonatal hypoglycemia and brain damage]. PMID- 1879781 TI - [Ambulatory diagnostic heart catheterization]. PMID- 1879782 TI - [Word recognition and confrontation naming in early diagnosis of dementia]. AB - Since early identification of dementia is very important, a simple inexpensive examination for its diagnosis is needed. A naming and recognition test was formulated for: examining factors affecting naming performance, comparing naming and recognition performance, and sampling spontaneous speech. The results were compared with those of the mini-mental test. Subjects were 7 men and 14 women (mean age 80 +/- 4.7) in the early stages of dementia, living in a senior citizen's home. The short mini-mental test differentiated between the groups, as did the newly formulated test. Language tests were shown to be of value in the accurate detection of dementia in its early stages. PMID- 1879783 TI - [Determination of pancreatic size by ultrasound in diabetics]. AB - Determination of pancreatic size by ultrasound in diabetics showed that the pancreas is smallest in Type 1 (IDDM) diabetes (7.15 +/- 0.55 cm), larger in Type 2 (9.71 +/- 0.81 cm), but significantly greater in nondiabetics (15.17 +/- 0.79 cm). In 10/12 patients referred because of reactive hypoglycemia there was insulin-resistance and the pancreas was smaller than 8 cm. There was no correlation between pancreatic size and duration of diabetes, body size, or body mass index. More normal controls of various ages are needed for definitive assessment. PMID- 1879784 TI - [Evaluation of a new Israel infant soy formula]. AB - A new infant soy formula has recently been developed in Israel and is being produced (Materna Tsimchit, Trima Industries, Kibbutz Ma'aborot). We compared its efficacy with that of a well-known imported soy formula (Isomil, Ross Laboratories, USA) in a prospective, randomized, double-blind study. 45 normal infants, aged 1-6 months, were monitored for over 2 months after the soy formula was started either because of cow-milk allergy or lactose intolerance. 22 received Materna Tsimchit and 23 Isomil. The study revealed no significant differences between the products with regard to compliance, behavior, symptoms, physical examination (including growth parameters and nutritional assessment), stool characteristics and complete blood counts. We conclude, given the limitations of the present study, that the new Israeli product is as effective as the foreign product. PMID- 1879785 TI - [Vascular injuries in children]. AB - Vascular trauma in children differs in some respects from that in adults. In infants and children the total blood volume is smaller, and despite effective compensatory mechanisms, critical blood loss is also smaller. Gentle and meticulous technical skill is needed to correct injuries of minute vessels and allow adequate blood flow. The use of synthetic tubes and materials is not recommended, as they do not lengthen as the child grows. Ischemia is a major factor influencing limb growth and function. 3 different types of vascular injuries operated on in the past year are presented. PMID- 1879786 TI - [Penetrating neck injuries]. AB - The frequency of penetrating neck injuries has increased in recent years. In 16 patients with such injuries treated during the past 2 years, neck exploration was performed immediately. In 4 there was destruction of the throat or trachea, in 3 a tear in the esophagus, in 1 a tear in the hypopharynx and in 1 a tear in the submandibular region penetrating the floor of the mouth. In 8 there was no damage to the neck organs. Of the 16, 1 died on the operating table from hemorrhage from multiple tears of the hypopharynx, the esophagus and the thyroid gland. 2 different approaches are used in dealing with penetrating neck injuries: immediate exploration, or the use of imaging methods to diagnose the degree of damage, followed by close supervision. In the light of our experience we advocate immediate neck exploration. PMID- 1879787 TI - [Primary epiphyseal osteomyelitis in children]. AB - A 4-year-old boy was hospitalized for suspected hematogenous osteomyelitis of the distal femur. Bone scan and repeated radiographs showed a rare condition, primary epiphyseal osteomyelitis. Needle biopsy and aspiration were negative. Penbritin and orbenil, 2 g of each, gave complete clinical and radiographic healing 7 weeks after initial treatment. PMID- 1879788 TI - [Renal effects of recombinant interleukin-2]. PMID- 1879789 TI - [Endothelin: a new vasoconstrictor of endothelial origin]. PMID- 1879790 TI - [Has schizophrenia an immunologic basis]. PMID- 1879791 TI - [Psychiatry in medicine: how to save a lot of money with a small investment; or: how to waste a lot of money by trying to cut edges?]. PMID- 1879792 TI - [Diagnostic evaluation and surgical treatment of stress incontinence in the female]. PMID- 1879793 TI - [Cognitive changes associated with depression]. PMID- 1879794 TI - [Pathophysiological changes in eating disorders]. PMID- 1879795 TI - [Intraocular, orbital and ocular adnexal lymphoid neoplasms]. PMID- 1879796 TI - [Diagnosing drinkers in general practice--secondary prevention by the family physician]. PMID- 1879797 TI - [Amenorrhea in female athletes]. PMID- 1879798 TI - [Soy-based formula in infant nutrition]. PMID- 1879799 TI - [Menopause and hormone replacement therapy in relation to atherosclerotic heart disease]. PMID- 1879800 TI - [Respiratory infections and the sudden infant death syndrome]. PMID- 1879801 TI - [Eating disorders]. PMID- 1879802 TI - [Effects of FOY-305 on post-operative reflux esophagitis in rats (I). Effects of FOY-305 on reflux esophagitis after total gastrectomy in rats]. AB - We investigated the effect of camostat mesilate (FOY-305), an oral protease inhibitor, on reflux esophagitis after total gastrectomy followed by an end-to side esophago-jejunostomy (Billroth-II) in rats. Effects of FOY-305 were compared with those of sodium alginate (AL-Na) and cimetidine. On the basis that esophageal ulceration occurred from post-operative day 5 in this model, rodents were fed with special chows containing test drugs from day 2 for 5 or 12 days in order to examine the prophylactic effects (Exp. I) and from day 7 for two weeks in healing experiments (Exp. II). In Exp. I, FOY-305 significantly prevented esophageal ulceration on post-operative days 7 and 14. However, AL-Na significantly prevented esophageal ulceration on post-operative day 7 but not on day 14. In Exp. II, FOY-305 had a remarkable therapeutic effect on esophageal ulceration on day 21. Food intake and body weight of rodents in the FOY-305 treated group were higher than those in the control group. In pathohistological studies, FOY-305 elicited an inhibitory effect on ulceration and induced esophageal mucosal regeneration at the ulceration sites. In contrast, AL-Na and cimetidine did not have any significant therapeutic effect. These results suggest that FOY-305 is an effective agent for the treatment of reflux esophagitis after total gastrectomy. PMID- 1879803 TI - [Effect of FOY-305 on post-operative reflux esophagitis in rats (II). Analysis of mechanism in the pathogenesis of reflux esophagitis after total gastrectomy in rats]. AB - Esophagitis after total gastrectomy has been associated with biliary and pancreatic reflux into the esophagus. The purpose of this study is to clarify the effect of FOY-305 on these factors in the esophagitis. We initially produced esophagitis in rats with total gastrectomy followed by an end-to-side esophago jejunostomy (Billroth-II). After treatment of FOY-305 on post-operative day 7 in this model, esophageal washout samples were analyzed for increases in activity of trypsin and total bile acid concentration. FOY-305 completely inhibited increases of trypsin activity in 2 and 4 hr, and it significantly (P less than 0.05) reduced bile acid concentration in 4 hr after initiating treatment. In addition, we evaluated the injurious effect of trypsin and sodium taurocholate (Tc-Na) on isolated esophagus of rats by measuring released tyrosine in the medium and used it as an index of the degree of injury. Tc-Na (3-fold of enteral bile acid concentration) inflicted only a slight injurious effect with negligible tyrosine release increases, and it did not show synergistic action when concomitantly used with trypsin. However, trypsin clearly induced increased tyrosine release from the esophageal mucosa, and this effect was significantly (P less than 0.001) inhibited by FOY-305 (50 microM). These results indicate that trypsin is one of the important factors in the pathogenesis of reflux esophagitis after total gastrectomy, and FOY-305 exerts a therapeutic effect by eliciting an inhibitory action against trypsin activity. PMID- 1879804 TI - [Effects of cholinergic drugs on delayed discrimination disruption by AF64A in rats]. AB - In a 2-lever operant chamber situation for food reinforcement, the effects of nicotine, arecoline and physostigmine on delayed discrimination responses in rats treated with ethylcholine mustard aziridinium ion (AF64A) were investigated. AF64A at 6 nmol, i.c.v., decreased the percentage of correct choices (% CR) at the delay time of 4 sec, and this effect depended on the delay time. On the other hand, AF64A at the same dose shortened the latency (LAT: the period from the end of the delay time to the initiation of lever-pressing responses) at the delay time of 16 sec, but this effect didn't depend on the delay time. Nicotine at 0.25 mg/kg, s.c., improved the decrease of % CR; and at 0.13-0.5 mg/kg, s.c., it shortened LAT at the delay time of 4 sec in rats treated with AF64A. Arecoline at 4 mg/kg, s.c., and physostigmine at 0.06-0.5 mg/kg, s.c., extended LAT, but both drugs showed no effects on % CR at the delay time of 4 sec in rats treated with AF64A. These results suggest that the present procedure might be useful for the evaluation of drug effects on memory in rats, and nicotine improved the delayed discrimination disruption induced by AF64A. PMID- 1879805 TI - [Effects of cernitin pollen extract (CN-009) on the isolated bladder smooth muscles and the intravesical pressure]. AB - Cernitin pollen extract (CN-009), extract from several pollen species, has been used for urinary dysfunction. As its mode of action has not been clarified, we investigated the action of CN-009 on the isolated bladder smooth muscles of rats, guinea pigs and cats and the intravesical pressure in female rats. CN-009 contracted isolated detrusor muscles of rats, guinea pigs and cats in a concentration-dependent manner. In the guinea pig detrusor muscle, the contractile effect of CN-009 was depressed by atropine, diphenhydramine and increased by cimetidine. In the rat detrusor muscle, the CN-009-induced contraction was depressed by atropine. In adult rats (11-23 weeks old) and aged rats (2 years old), CN-009 showed a dose-dependent increase of intravesical pressure to the same extent in spite of the fact that the aged rats had a lower responsiveness to acetylcholine. In adult rats, the CN-009-induced increase of intravesical pressure was reduced completely by atropine and partly reduced by phentolamine and guanethidine. Three weeks consecutive oral administration of CN 009 tended to increase the basal intravesical pressure and tended to elevate the isoproterenol-induced decrease and serotonin-induced increase in the intravesical pressure. These results suggest that CN-009 contracts the detrusor muscle, a process that is mainly mediated by muscarinic receptor activation. The contraction induced by CN-009 of detrusor muscle causes the increase of intravesical pressure. PMID- 1879806 TI - [Effects of 3-hydroxymethyl-2-methylimidazo [2, 1-b] benzothiazole (NIK-228) on gastric acid secretion and various experimental peptic ulcers in rats]. AB - We examined the antisecretory and antiulcer activities of NIK-228 in rats. Male Wistar rats (200 to 250 g) were used under 24 to 48 hr fasted (without water) conditions. NIK-228 and famotidine were administered orally 1 hr before pylorus ligation, stress or each ulceration inducer. Both NIK-228 (10 to 100 mg/kg) and famotidine (0.3 to 3 mg/kg) dose-dependently inhibited gastric secretion in pylorus ligated rats. Water-immersion stress-, indomethacin- or pylorus ligation (Shay)-induced gastric ulcers were dose-dependently inhibited by NIK-228 (10 to 100 mg/kg), but only water-immersion stress and indomethacin induced ulcers were dose-dependently inhibited by famotidine (0.03 to 3 mg/kg). Ethanol- and 0.6 N HCl-induced gastric lesions were remarkably inhibited by NIK-228 (ED50 = 2.7 and 5.6 mg/kg), but tended to be inhibited also by famotidine (0.3 to 3 mg/kg). Cysteamine-induced duodenal ulcer was inhibited significantly by NIK-228 (30, 100 mg/kg) or famotidine (3 mg/kg). NIK-228 may produce its antiulcer effects via antisecretory and cytoprotective effects. These results suggest that NIK-228 has antisecretory and antiulcer activities. PMID- 1879807 TI - [Analysis of stress-strain curves in the rat molar periodontal ligament following administration of beta-aminopropionitrile (BAPN)]. AB - To understand the function of the periodontal ligament as a tooth support, stress strain curves obtained from the transverse section of the mesial root of the rat mandibular first molar were analyzed following administration of BAPN, known as an inhibitor of collagen cross-linking. An experimental group of rats took drinking water containing 0.2% of BAPN ad libitum for 20 days. Radiographs of the transverse section of the molar root were processed by an image analyzer. Mechanical testing was performed by pushing the tooth out of the surrounding alveolar bone at a loading speed of 7 mm/min in an extrusive direction. Doses of BAPN ranged from 19 to 29 mg/100 g bw/day during the experimental period. By the analysis of stress-strain curves, it was found that the maximum shear stress, the elastic stiffness and the failure strain energy density decreased respectively to 42, 43 and 43 percent of the control values following administration of BAPN. However BAPN did not cause a significant change in the maximum strain. It is supposed that the changes in the mechanical properties of the ligament were caused by the inhibition of cross-linking of periodontal collagen fibers. PMID- 1879808 TI - Bone marrow trephine interpretation: diagnostic utility and potential pitfalls. AB - Good quality paraffin-embedded sections can be obtained from bone marrow trephines, allowing the routine use of these biopsies in diagnostic histopathology. Trephines are superior to aspirates, especially for the assessment of marrow cellularity, the extent and pattern of tumour infiltration and the cell type. Bone marrow biopsies are useful in several areas, e.g. non haematological disorders, myelodysplasia, the myeloproliferative group, lymphomas and leukaemias, which are briefly discussed below. Further advances in interpretation are likely with more frequent use of bone marrow trephines. PMID- 1879809 TI - Bone marrow diagnosis in lymphoproliferative disorders: comparison of results obtained from conventional histomorphology and immunohistology. AB - In this study we have investigated 313 bone marrow biopsies from 280 patients with lymphoproliferative disorders. Trephines were sectioned transversely to obtain one cylinder for cryostat sectioning and immunostaining and a second for histomorphological evaluation using a plastic-embedding technique. The results obtained by histomorphological and immunohistological evaluation were compared for their contribution to staging and classification. Using both techniques, bone marrow involvement was seen in 3/43 (7.0%) biopsies from patients with Hodgkin's disease and in 193/270 (71.5%) cases with non-Hodgkin's lymphoma, including multiple myeloma and acute lymphocytic leukaemia. Immunohistology proved superior in detecting minimal mainly interstitial bone marrow infiltration in 15 leukaemia/lymphoma cases. Biopsies showing infiltration with both methods (n = 157) were re-examined for classification of lymphomatous infiltrates. Whereas immunohistology did not provide additional information in cases with Hodgkin's disease and myeloma, this method was crucial for establishing the definitive diagnosis in a number of cases with acute lymphocytic leukaemia and non-Hodgkin's lymphoma. In all of six leukaemia cases, in which no or inadequate material was available for immunophenotyping of cell suspensions, immunohistology clearly defined the subtype. In the 140 cases of non-Hodgkin's lymphoma the majority of cases (76.4%) were identically classified. In some cases, with important prognostic and therapeutic implications, immunohistology alone provided the definitive diagnosis: T-cell lymphoma (n = 2), hairy cell leukaemia (n = 2) and centrocytic non-Hodgkin's lymphoma (n = 3). Bone marrow immunohistology is, therefore, an important supplement for classical lymphoma/leukaemia diagnosis. The differences observed between histomorphology and immunohistology emphasize the importance of lymph node biopsy in lymphoma classification. PMID- 1879810 TI - Immunophenotyping of Nigerian cases of non-Hodgkin's lymphomas on paraffin sections. AB - One hundred cases of routinely fixed and processed non-Hodgkin's lymphoma from Nigeria were immunostained with a small panel of monoclonal antibodies against B , T- and macrophage antigens. The aims of the study were to assess the suitability of stored material from a country like Nigeria for immunohistochemical examination and the ability of the antibody panel to evaluate the distribution of B- and T-cell neoplasms. Eighty-seven of the 100 cases gave interpretable immunostaining, with 75 being B-cell and 12 T-cell neoplasms. Eighty-seven of the 100 cases gave interpretable immunostaining, with 75 being B cell and 12 T-cell neoplasms. There were no tumours of macrophage lineage. Four cases gave satisfactory staining of reactive lymphoid cells but no reactivity with malignant cells and thus were not phenotyped. The remaining nine cases gave no staining of neoplastic or reactive cells, suggesting that they were unsuitable for immunohistochemical study, presumably because of inappropriate fixation and handling. We concluded that a panel of three monoclonal antibodies is suitable for routine immunostaining of conventionally fixed and processed blocks in Third World countries and will give diagnostically useful information in approximately 95% of cases. PMID- 1879811 TI - Demonstration of oestrogen and progesterone receptors in freeze-dried, paraffin embedded sections of breast cancer. AB - Immunohistochemical evaluation of oestrogen and progesterone receptors is of importance in evaluating human breast tumours. Staining techniques can be performed on snap-frozen, cryostat-cut tissues or, as recently reported, on formalin-fixed, paraffin-embedded tissues. These methods are, however, limited by several drawbacks, including difficulties in retrospective studies and in storage of the material, and the relatively high frequency of false negative results for chemically fixed specimens. We therefore investigated the application of freeze drying technology to assess the feasibility and reliability of this technique as an alternative method for diagnostic breast pathology. Morphological and immunohistochemical studies were performed on snap-frozen, freeze-dried and paraffin-embedded tissue obtained from 16 cases of benign and malignant breast neoplasms. Our results showed good preservation of tissue morphology, similar to standard formalin fixation, and excellent preservation of antigenic reactivity of nuclear receptors, comparable to that obtained with cryostat sections. We therefore suggest that freeze drying and paraffin embedding of frozen tissue blocks is equivalent or even preferable to formalin fixation for the demonstration of oestrogen and progesterone receptors, at least in the case of small tumours. PMID- 1879812 TI - Smooth muscle tumours of the external genitalia: clinicopathological analysis of a series. AB - Smooth muscle tumours of the external genitalia (vulva, scrotum and nipple) are uncommon and have received little attention in the literature. Given their purported close relationship to cutaneous (pilar) leiomyomatous lesions, we have studied 32 cases (18 vulva, 10 scrotum, four nipple) from 31 patients in order to compare clinicopathological features at the different sites. Only those in the nipple were comparable in size and histology to pilar leiomyomas. Vulval and scrotal tumours tended to be much larger and better circumscribed. Purely epithelioid lesions were only identified in the vulva (two cases) and at this site myxoid change and hyalinization were substantially more common. Almost all cases showed immunohistochemical evidence of muscle differentiation. On histological grounds, nine cases were classified as leiomyosarcoma (six scrotum, three vulva) but only one of the five with follow-up has led to the patient's death. With the exception of nipple lesions, which are particularly uncommon, we would not support the traditional inclusion of genital smooth muscle tumours under the general heading of cutaneous leiomyoma/sarcoma, as vulval and scrotal lesions are clinicopathologically quite different. PMID- 1879813 TI - Stereological estimates of nuclear volume in the prognostic evaluation of primary flat carcinoma in situ of the urinary bladder. AB - Primary, flat carcinoma in situ of the urinary bladder is rare and its behaviour is unpredictable. The aim of this retrospective study was to obtain base-line data and investigate the prognostic value of unbiased, stereological estimates of the volume-weighted mean nuclear volume, nuclear vv, in 78 bladder biopsies from 22 patients with primary flat carcinoma in situ (Bergkvist grades III-IV). On average, nuclear vv was 77 microns 3 in nine biopsies with morphologically normal urothelium, 292 microns 3 in 56 isolated primary lesions and 266 microns 3 in lesions of luminal urothelium in 13 biopsies with co-existing invasive carcinoma. No recognizable developmental pattern of nuclear vv in relation to the time course of disease was found. Nuclear volume in the first biopsy was of the same magnitude in lesions with and without co-existing invasive carcinoma (2P = 0.55), and in lesions with short and long duration of invasion-free period (2P greater than 0.20). Nuclear vv in the first biopsy did not differ between patients who survived and those who died from their primary flat carcinoma in situ (2P = 0.07). Dividing the patients on the basis of the group median of the first biopsy showing flat carcinoma in situ (nuclear vv = 261 microns 3), the survival was the same in patients with nuclear vv above and below the cut-off point (2P = 0.16). However, the survival curves showed a tendency to differ in the first 2-8 years of observation. Stereological estimates of nuclear vv provide objective, quantitative information, but their prognostic value in patients with primary flat carcinoma in situ of the bladder needs further clarification in larger data bases. PMID- 1879814 TI - Germ cell expression of placental alkaline phosphatase in male pseudohermaphroditism. AB - We have reviewed testes removed from 14 individuals with male pseudohermaphroditism (13 with androgen insensitivity and one with 17 alpha hydroxylase deficiency) and have studied staining for placental alkaline phosphatase in germ cells. Placental alkaline phosphatase positivity was identified in fetal and premature neonatal controls but not in cryptorchid males or normal autopsy control material from boys older than 6 months. It was present in autopsy testes younger than 6 months and cases of androgen insensitivity in boys younger than 8 months, suggesting immaturity. It was also expressed in two patients with male pseudohermaphroditism aged 5 years and 14 years, both of whom had intra-tubular germ cell neoplasia by morphological criteria. Our study confirms the use of placental alkaline phosphatase as a marker of germ cell neoplasia in this specific group who are at high risk of malignancy. PMID- 1879815 TI - Uterus-like mass of the ovary associated with endometrioid carcinoma. AB - We describe a solid and cystic right ovarian mass removed from a 38-year-old woman. The solid component, which had a central cavity lined by endometriotic tissue and surrounded by a thick muscle wall, strongly resembled a miniature uterus. The contiguous cystic mass was an endometrioid carcinoma. We review the literature and discuss the theories of histogenesis of uterus-like ovarian masses. PMID- 1879816 TI - The sweat gland in cutaneous vasculitis. AB - Cutaneous vasculitis commonly presents as palpable purpura, and the late stages may become nodular, bullous, infarcted and ulcerated. Involvement of sweat glands in vasculitic lesions has not been previously described. In a detailed study of 48 cases of non-infarcted cutaneous vasculitis, 18 (36%) revealed morphologically abnormal sweat glands. Basal cell degeneration, necrosis, regeneration and basal cell hyperplasia were found in the excretory ducts. Necrosis of the secretory gland was seen either as apoptosis involving the clear cells or as a whole gland necrosis involving both cell types. This unusual feature has only been described in association with coma, commonly due to barbiturate and carbon monoxide poisoning. Its presence in non-infarcted vasculitis adds support to the hypoxia/ischaemia hypothesis. The functional impact of such lesions in widespread cutaneous vasculitides requires further study. PMID- 1879817 TI - Metastatic melanoma mimicking primary bronchial melanoma. AB - Primary malignant melanoma of the bronchus is an extremely rare neoplasm. The criteria required to establish a bronchial origin include junctional change and invasion of intact bronchial mucosa by melanoma cells. A case of metastatic melanoma demonstrating such changes is described, so casting doubt on the validity of these criteria. PMID- 1879818 TI - Pre-sacral carcinoid tumour. PMID- 1879819 TI - Immunolocalization of prealbumin (transthyretin) in renal cell carcinoma. AB - Fourteen primary and nine metastatic renal cell carcinomas were examined with a commercially available antibody against prealbumin (transthyretin) using the avidin-biotin-peroxidase complex (ABC) technique. Twenty-two of the 23 tumours expressed prealbumin, and in 16 of them more than 50% of the tumour cells showed immunoreactivity. The same tumours were subjected to immunostaining with antibodies against low molecular weight keratin, carcino-embryonic antigen, S-100 protein and epithelial membrane antigen for comparison. We conclude that prealbumin, which was absent in 14 adenocarcinomas from other organs, should be included in the panel of markers for differentiating metastatic adenocarcinoma of renal origin from those of other primary tumours. PMID- 1879820 TI - Helicobacter pylori in Barrett's oesophagus. Gruppo Operativo per lo Studio Delle Precancerosi Esofagee (GOSPE)--Precancerous Lesions of the Oesophagus Task Force, Italy. PMID- 1879821 TI - Subcutaneous sacrococcygeal ependymoma with incidental glomus coccygeum. PMID- 1879822 TI - Signet-ring cell melanoma: light microscopic, immunohistochemical and ultrastructural features. PMID- 1879823 TI - Multiple myeloma showing signet-ring cell change. PMID- 1879824 TI - Viral myocarditis. PMID- 1879825 TI - An intronic duplication in the alanine: glyoxylate aminotransferase gene facilitates identification of mutations in compound heterozygote patients with primary hyperoxaluria type 1. AB - We report here the identification of a duplication within the first intron of the gene encoding human alanine:glyoxylate aminotransferase (AGT); this duplication is closely linked to two point mutations associated with peroxisome-to mitochondrion mistargeting of AGT in primary hyperoxaluria type 1 (PH1) patients. Polymerase chain reaction amplification of regions of the AGT gene including the insertion site from individuals heterozygous for this duplication, produces allele-specific fragments of different sizes. We have taken advantage of this to identify a nonsense mutation within a non-expressed allele of a compound heterozygote PH1 patient with mitochondrial AGT. PMID- 1879826 TI - Linkage mapping of D21S171 to the distal long arm of human chromosome 21 using a polymorphic (AC)n dinucleotide repeat. AB - An (AC)n repeat within the anonymous DNA sequence D21S171 was shown to be highly polymorphic in members of the 40 Centre d'Etude du Polymorphisme Humaine (CEPH) families. Ten different alleles at this marker locus were detected by electrophoresis on polyacrylamide gels of DNA amplified by the polymerase chain reaction (PCR) using primers flanking the (AC)n repeat. The observed heterozygosity was 66%. PCR amplification of DNA from somatic cell hybrids mapped D21S171 to human chromosome 21, and linkage analysis localized this marker close to the loci CD18, PFKL, D21S113 and D21S112 in chromosomal band 21q22.3. In CEPH family 12 a de novo allele has been observed in a maternally derived chromosome. PMID- 1879827 TI - Spinocerebellar ataxia: multipoint linkage analysis of genes associated with the disease locus. AB - Spinocerebellar ataxia (SCA) was studied in a seven-generation (Schut-Swier) kindred using linkage analysis to localize further the autosomal dominant, HLA linked, disease-producing SCA1 locus relative to four other loci that map to the short arm of human chromosome 6. Genotypes for each locus were determined in as many individuals as possible from a total of 162 affected and unaffected family members that were studied. A maximum pairwise lod score of 8.52 (theta m = 0.10, theta f = 0.22) for linkage between SCA1 and HLA-A was observed. Multipoint linkage analyses for the SCA1, HLA-A, F13A, D6S7, and GLO1 loci revealed that the SCA1 locus is most probably located telomeric to HLA-A, with a likely location between HLA-A and F13A. PMID- 1879828 TI - Persistence of two Y chromosomes through meiotic prophase and metaphase I in an XYY man. AB - Studies of spermatogenesis in an XYY male, presenting at a subfertility clinic, confirm the tendency for the germ cells to lose the second Y chromosome but for some XYY cells to reach metaphase I (MI). Light microscope studies of MI revealed the presence of YY bivalents and EM studies of microspread, silver-stained pachytene stages showed 30% of the cells to have two Y chromosomes; 13 out of 16 of these showing a YY synaptonemal complex. Strikingly, the Y axes show only partial synapsis; in no case was synapsis of the long arm heterochromatic regions apparent. PMID- 1879829 TI - Orosomucoid (ORM 1) subtyping and formal genetics. AB - Orosomucoid (ORM) phenotyping has been performed in 141 families with 407 children from southwest Germany. Eight families were observed in which duplicated ORM1 genes, F1F2, F1F3, segregated. The family data gave no information about the presence of tandemly duplicated ORM1 F1F4 and ORM1 F1F5 genes. To date, the segregation of the phenotypes of the children agrees with the extended formal model: two ORM1 loci with two common (*F1, *S) and several rare (*F1F2, *F1F3, *F4, *F5) alleles. The parental allele frequencies were calculated by gene counting as ORM1 *F1 = 0.5781, *S = 0.3901, *F1F2 = 0.0195, *F4 = 0.0053, *F1F3 = 00.0035, *F5 = 0.0035. PMID- 1879830 TI - A polymorphic region defined by pCN2 (the 3' nontranslated region of N-ras) maps to chromosome 9cen-p12. AB - Abnormalities of chromosome 9p have been reported in human leukemias and lymphomas, and in cell lines lacking the enzyme methylthioadenosine phosphorylase. It has been shown pCN2, the 3' nontranslated region of the N-ras oncogene, crosshybridizes with unknown DNA segments on chromosome 6, 9p, and 22, in addition to the N-ras oncogene itself on chromosome 1p. To use pCN2 to study chromosome 9p abnormalities in malignancies, we undertook to localize the pCN2 crosshybridizing region in chromosome 9p. By analyzing the copy numbers of the pCN2 crosshybridizing bands associated with chromosome 9p among various chromosomally aberrant human cell lines, we mapped the pCN2 hybridizing region to 9cen-p12. Since there is no other available probe in this region, pCN2 should prove very useful in studying abnormalities of chromosome 9p in human malignancies. PMID- 1879831 TI - Cytogenetic studies in human sperm. AB - Sperm chromosome studies were performed in seven males. One of them had a history of exposure to lysergic acid (LSD) although he was free of the drug for 1 year before the study began. Sixteen ejaculates provided a total of 555 fully analyzable sperm cells. The overall frequency of hyperhaploid sperm cells was 2% and that of structural abnormality 3.6%. The most common structural abnormality was chromosome breaks followed by small chromosome fragments of unknown origin. Three chromosome breakpoints, 10q25, 2q21, and 9q21, were involved twice in different chromosome or chromatid type aberrations. Two of these, 10q25 and 2q21, correspond to chromosomal locations known as common fragile sites. PMID- 1879832 TI - Greig syndrome associated with an interstitial deletion of 7p: confirmation of the localization of Greig syndrome to 7p13. AB - An 11-month-old infant with Greig cephalopolysyndactyly syndrome and mild developmental delay is described. High-resolution chromosomal analysis showed a de novo interstitial deletion of chromosome 7p with breakpoints located at p13 and p14. Cytogenetic analysis of polymorphisms of the heterochromatin in the pericentromeric region suggested the deleted chromosome was of paternal origin. This case confirms the localization of Greig syndrome to 7p13 and emphasizes the importance of performing cytogenetic studies on patients with Mendelian disorders who have unusual findings or cognitive abnormalities in a disorder usually associated with normal intellect. Review of clinical features in published reports of patients with a deletion involving 7p13 showed a number to have features overlapping with Greig syndrome. Because of this, we suggest that cytogenetic aberrations, particularly chromosomal microdeletions, may represent a significant etiology for Greig syndrome. PMID- 1879833 TI - Mutation analysis of glucose-6-phosphate dehydrogenase (G6PD) variants in Costa Rica. AB - Glucose-6-phosphate dehydrogenase (G6PD) deficiency has previously been reported among both the black and white populations of Costa Rica. All 28 G6PD A- samples were found to be of the common G6PD A-376G/202A type. A previously described mutation associated with nonspherocytic hemolytic anemia, G6PD Puerto Limon, was found to be due to a G----A transition at nucleotide (nt) 1192, causing a glu--- lys substitution. Mutations in this region of the G6PD molecule seem invariably to be associated with chronic hemolytic anemia. G6PD Santamaria had been described previously in two unrelated white subjects. We found that both did, indeed, have the same mutations. In this variant the A----G substitution at nt 376 that is characteristic of G6PD A was present, but an A----T mutation at nt 542, apparently superimposed on the ancient G6PD A mutation, resulted in an asp-- -val substitution. Thus, the gain of a negative charge at amino acid 126 was counterbalanced by the loss of a charge at amino acid 181, giving rise to a variant with the G6PD A mutation but with normal electrophoretic mobility. PMID- 1879834 TI - Status of the search for a major genetic locus for affective disorder in the Old Order Amish. AB - We have resumed the search for an autosomal linkage with affective disorder in the Old Order Amish and report the pairwise linkage results after screening 185 marked loci. No positive evidence of genetic linkage was found, and we estimate that roughly 23% of the autosomal genome has been excluded from linkage. PMID- 1879835 TI - Labeling of the centromeric region on human chromosome 8 by in situ hybridization. AB - Probe DNA that binds preferentially to the centromeric region of human chromosomes 8 was synthesized. Alpha satellite probe DNA molecules were selectively amplified from sorter-purified human chromosomes 8 by in vitro DNA amplification using the polymerase chain reaction (PCR). Probe labeling was performed during PCR by incorporation of biotinylated deoxyuridine. In situ hybridization of unpurified probe DNA comprised of alpha satellite monomer and higher molecular weight DNA fragments with metaphase chromosome spreads showed binding to the centromeric regions of numerous chromosomes. However, blocking with unlabeled total human alphoid DNA dramatically reduced crosshybridization to chromosomes other than 8. Under these conditions, the degenerate probe DNA allowed unambiguous visualization of domains occupied by centromeric DNA of chromosome 8 in metaphase spreads and interphase cell nuclei, thus greatly facilitating the detection of numerical chromosome aberrations in tumor cells. In situ hybridization of size-fractionated alpha satellite DNA identified the monomeric fraction as the major cause of crosshybridization. Alpha satellite dimers and higher molecular weight DNA fragments showed relatively high specificity for human chromosomes 8. PMID- 1879836 TI - Isodicentric X chromosome in a patient with Turner syndrome--implications for localization of the X-inactivation center. AB - Cytogenetic analyses have previously shown that the region Xq11.2-q21 is retained in all structurally abnormal X chromosomes. From these observations the conclusion has been drawn that this "critical region" on the proximal long arm of the X chromosome contains the locus controlling X-inactivation. Structurally abnormal X chromosomes without the X-inactivation center would allow nullisomy, disomy, or trisomy for genes on the X chromosome, and this condition is presumed nonviable. We studied a 28-year-old woman with primary amenorrhea and features of Turner syndrome who had an unusual isodicentric chromosome of the short arm of X. This patient provided us with the opportunity to more closely define the location of the X-inactivation center. High resolution chromosome analysis showed a 46,X,idic(X)(pter----q13.2::q13.2----pter) chromosome pattern in 94% of her cells and a 45,X complement in 6%. Replication studies showed this derivative X chromosome to be late-replicating (inactive) in all cells analyzed. DNA analysis confirmed the breakpoint of the isodicentric chromosome to be proximal to PGK1. Based on these results, the locus for the X-inactivation center can be refined to be within Xq11.2-q13.2. PMID- 1879838 TI - Cytogenetic studies on MIC gas-exposed persons in Bhopal. PMID- 1879837 TI - Isolated lissencephaly sequence associated with a microdeletion at chromosome 17p13. AB - DNA markers YNZ22.1, YNH37.3, 144D6 and VAW508 were studied in a patient with the isolated lissencephaly sequence (ILS). A normal karyotype was found in the patient. The DNA of the patient showed deletions of markers YNZ22.1 and YNH37.3. This is the first report of a case of ILS (with grade 3 lissencephaly) with a submicroscopic deletion. The presence of a microdeletion in 17p13 in an ILS patient indicates that Miller-Dieker syndrome and ILS have a common etiology. PMID- 1879839 TI - A controller for regulation of mean arterial blood pressure using optimum nitroprusside infusion rate. AB - Automation of drug delivery for control of mean arterial blood pressure is highly desirable in a number of clinical applications. An integrating self-tuning control strategy for control of mean arterial blood pressure using sodium nitroprusside is presented. Next to robust performance, the most attractive feature of the controller is its capability to optimize the quantity of infused medication without introducing a bias in the blood pressure level; a problem that existed in some of the other adaptive control strategies that have been proposed previously. Further, the controller design requires only the knowledge of the pure delay and the order of the transfer function describing the patient's response to the medication; it does not require that the entire transfer function be specified. The derivation of the controller is not based on the patient response to sodium nitroprusside; indeed, it is a general adaptive control strategy for control of systems with transport delay. The controller performs robustly in the presence of variations in the patient response and successfully controls the pressure at the desired level. The ability of this strategy to reduce the amount of infused medication makes it potentially attractive for use in clinical applications, as large doses or long term use of sodium nitroprusside can adversely affect central nervous system and hematopoietic tissues. PMID- 1879840 TI - A simple analytical solution to the three-compartment pharmacokinetic model suitable for computer-controlled infusion pumps. AB - The disposition of many drugs following an intravenous bolus injection can be described by a biexponential or triexponential equation. Computer-controlled infusion pumps have been developed which dose intravenous drugs based on models of drug disposition. These pumps can maintain steady plasma drug concentrations and facilitate controlled increases and decreases in drug concentration, enhancing titration of intravenous drugs. Several investigators have proposed analytical solutions to the biexponential and triexponential disposition functions for use in computer-controlled infusion pumps. Because of the complexity of these analytical solutions, other investigators have used numerical techniques to approximate the analytical solution. We have derived an extremely simple analytical solution to polyexponential disposition functions. This solution simplifies both the prediction of the plasma drug concentration by a computer-controlled infusion pump and the stepwise calculation of the infusion rate required to maintain constant plasma drug concentrations. PMID- 1879841 TI - Model studies of extracellular electrograms arising from an excitation wave propagating in a thin layer. AB - Extracellular potentials were calculated for a wave of activation propagating through a thin layer of tissue. Sources were represented on the basis of the bidomain model, with the observation point at the tissue surface. Calculated potentials were found to be insensitive to the length of the wavefront if it passed under the recording electrode provided its length exceeded 1 mm, but to decrease rapidly when the wave passed to a side of the electrode. Contributions of source regions with a lateral displacement from the electrode greater than about 0.3 mm were substantially diminished. The effects of the thickness of the layer and velocity of propagation on amplitude was investigated. PMID- 1879842 TI - A nystagmus strategy to linearize the vestibulo-ocular reflex. AB - This paper addresses two important aspects of the vestibulo-ocular reflex (VOR). First, the linear range of ocular responses is much more extensive than expected from the characteristics of central pathways (CNS), and this is shown to result directly from early convergence of 'fast' and 'slow' premotor signals in the central processes, associated with significant and intermittent changes in functional connectivity (effective structural modulation). Second, the presence of such structural modulation implies that responses must be analyzed using transient analysis techniques, rather than previous steady state approaches, in order to properly evaluate reflex dynamics. Simulation results with a recent model of the VOR are used to illustrate the arguments. Relying on known inter connections between saccadic burst circuits in the brainstem, and the ocular premotor areas of the vestibular nuclei, a viable strategy for the timing of nystagmus events is proposed. The strategy easily reproduces the characteristic changes in vestibular nystagmus with the amplitude of head velocities, and with the frequency of passive head oscillation. PMID- 1879843 TI - The estimation of tube wall compliance using acoustic input impedance. AB - An acoustic-electric analog and transmission line theory have been used to examine acoustic wave propagation in a tube with a compliant wall. The input impedance (i.e., input pressure-flow) has been simulated using a distributed element model. A relative minimum and maximum, denoted by fr and f2, respectively, that are independent of tube length have been identified theoretically and confirmed experimentally from input impedance measurements on a compliant tube. A method has been devised which uses measured values of fr and f2 to deduce the tube wall properties from the theoretical model. This method has been validated on a tube with known wall properties determined using standard methods. In practice, the input impedance is measured through a short section of rigid connecting pipe. In this case fr remains constant while f2 is reduced. This reduction can be accounted for by the volume compliance of the gas within the lumen of the rigid pipe. The theory could have useful applications such as estimating the wall properties of the airways from noninvasive measurements made through the mouth. PMID- 1879844 TI - A simple electrical-mechanical model of the heart applied to the study of electrical-mechanical alternans. AB - Recent evidence has shown that a subtle alternation in the surface ECG (electrical alternans) may be correlated with the susceptibility to ventricular fibrillation. This paper presents evidence that a mechanical alternation in the heart beat (mechanical alternans) generally accompanies electrical alternans. A simple finite-element computer model, which emulates both the electrical and mechanical activity of the heart, is presented. A pilot animal study is also reported. The computer model and the animal study both found that 1) there exists a regime of combined electrical-mechanical alternans during the transition from a normal rhythm towards a fibrillatory rhythm, 2) the detected degree of alternation is correlated with the relative instability of the rhythm, and 3) the electrical and mechanical alternans may result from a dispersion in local electrical properties leading to a spatial-temporal alternation in the electrical conduction process. PMID- 1879845 TI - A comparison of four new time-domain techniques for discriminating monomorphic ventricular tachycardia from sinus rhythm using ventricular waveform morphology. AB - Electrical management of intractable tachycardia via implantable antitachycardia devices has become a major form of therapy. Newly advanced methods of ventricular tachycardia detection propose examination of changes in intraventricular electrogram morphology in addition to or in combination with earlier rate-based detection algorithms. Unfortunately, most of the proposed morphology analysis techniques have computational demands beyond the capabilities of present devices or may be adversely affected by amplitude and baseline fluctuations of the intraventricular electrogram. We have designed four new computationally efficient time-domain algorithms for distinguishing ventricular electrograms during monomorphic ventricular tachycardia (VT) from those during sinus rhythm using direct analysis of the ventricular electrogram morphology. All four techniques are independent of amplitude fluctuations and three of the four are independent of baseline changes. These new techniques were compared to correlation waveform analysis, a previously proposed method for distinction of VT from sinus rhythm. Evaluation of these four new algorithms was performed on data from 19 consecutive patients with 31 distinct monomorphic ventricular tachycardia morphologies. Three of the algorithms performed as well or better than correlation waveform analysis but with one-tenth to one-half the computational demands. PMID- 1879846 TI - Alignment methods for averaging of high-resolution cardiac signals: a comparative study of performance. AB - Accurate signal estimation by means of coherent averaging techniques needs temporal alignment methods. A known low-pass filtering effect is yielded when alignment errors are present. This is very critical in the estimation of low level high-frequency potentials in high-resolution ECG analysis. A comparative study of the performance of three alignment methods (the double-level method, a new time-delay estimation method based on normalized integrals, and matched filtering) is presented in this paper. A real signal and additive random noise for several signal-to-noise ratios (SNR's) are selected to make an ensemble of computer-simulated beats. The relation between the standard deviation of temporal misalignment versus SNR is discussed. A second study with real ECG signals is also presented. Several morphologies of QRS and P waves are tested. The results are in agreement with the computer simulation study. Nevertheless, the power spectrum of the noise process can affect the results. Matched filter estimation has been tested in the presence of power line interference (50 Hz), with poor results. An application of the three alignment methods as a function of the SNR is proposed. The new time-delay estimation method has been observed to be robust, even in the presence of nonwhite noise. PMID- 1879847 TI - Statistical analysis of collagen alignment in ligaments by scale-space analysis. AB - Injuries to ligaments in the knee are common in sports and other physical activities. Some clinical methods are available for qualitatively evaluating the degree of ligament injury and healing. It is, however, desirable to objectively assess the healing of ligaments and to predicate optimal treatment on quantitative measurements of their structure. Information such as areas of coverage and spatial orientations of collagen fibrils, for example, may provide important information about the internal structure of ligament tissues. Since normal ligament tissues are made up of collagen fibrils which are highly organized, they can be considered as oriented piecewise linear patterns. In this paper, we propose a computational technique for statistical analysis of collagen alignment in ligament images using the scale-space approach. In this method, a ligament image is preprocessed by a sequence of filters which are second derivatives of two-dimensional Gaussian functions with different scales. This gives a set of zero-crossing maps (the scale space) from which a stability map is generated. Significant linear patterns are captured by analyzing the stability map. The directional information in terms of orientation distributions of the collagen fibrils in the image and the area covered by the fibrils in specific directions are extracted for statistical analysis. Examples illustrating the performance of this method with scanning electron microscope images of the collagen fibrils in healing rabbit medial collateral ligaments are presented in this paper. PMID- 1879848 TI - Modern spectral analysis techniques for blood flow velocity and spectral measurements with pulsed Doppler ultrasound. AB - Four spectral analysis techniques were applied to pulsed Doppler ultrasonic quadrature signals to compare the relative merits of each technique for estimation of flow velocity and Doppler spectra. The four techniques were 1) the fast Fourier transform method, 2) the maximum likelihood method, 3) the Burg autoregressive algorithm, and 4) the modified covariance approach to autoregressive modeling. Both simulated signals and signals obtained from an in vitro flow system were studied. Optimal parameter values (e.g., model orders) were determined for each method, and the effects of signal-to-noise ratio and signal bandwidth were investigated. The modern spectral analysis techniques were shown to be superior to Fourier techniques in most circumstances, provided the model order was chosen appropriately. Robustness considerations tended to recommend the maximum likelihood method for both velocity and spectral estimation. Despite the restrictions of steady laminar flow, the results provide important basic information concerning the applicability of modern spectral analysis techniques to Doppler ultrasonic evaluation of arterial disease. PMID- 1879849 TI - Mean-square error due to gradiometer field measuring devices. AB - Gradiometers use spatial common mode magnetic field rejection to reduce interference from distant sources. They also introduce distortion that can be severe, rendering experimental data difficult to interpret. Attempts to recover the measured magnetic field from the gradiometer output will be plagued by the nonexistence of a spatial function for deconvolution (except for first-order gradiometers), and by the high-pass nature of the spatial transform that emphasizes high spatial frequency noise. Goals of a design for a facility for measuring biomagnetic fields should be an effective shielded room and a field detector employing a first-order gradiometer. PMID- 1879850 TI - Servo-controlled indenter for determining the transverse stiffness of ventricular muscle. AB - Regional ventricular wall stress is a critical determinant of cardiac function. There are, however, no validated methods for accurately estimating this stress. We have shown in the isolated ventricular septum that, during steady-state indentations, the transverse stiffness (the ratio of indentation stress [pressure acting on indenter face] to indentation strain [amount of indentation/nonindented thickness]) can be used as an estimate of the in-plane wall stress. Because of the long acquisition time for those transverse stiffness determinations, it was not possible to follow changes in wall stress over a single contraction. We recently developed a dynamic indentation system that can determine transverse stiffness in as little as 10 ms, allowing estimation of wall stress over a single contraction cycle. The apparatus consists of an indentation probe coupled to a linear motor. This indentation system was tested on two beating canine ventricular septa that were mounted in a biaxial system the could apply strains in the plane of the septa and measure the resulting in-plane stresses. The probe indented the septa with peak displacements of 0.1-0.5 mm at frequencies of 20 and 50 Hz. The transverse stiffness was calculated as the slope of the relation between the indentation stress and indentation strain during each high-frequency indentation. Consistent with earlier studies, the transverse stiffness was related to the inplane stress. In contrast to earlier studies, however, these dynamic transverse stiffness determinations could be made during a single contraction. Thus, dynamic transverse stiffness determinations allow estimation of wall stress in the isolated septa by minimal surface contact, and may lead to methods for estimating wall stress in the intact heart. PMID- 1879851 TI - A programmable data acquisition and control system for magnetic resonance imaging: application to mutually coupled surface coil arrays and temperature monitoring. AB - A programmable data acquisition and control system was developed for use in conjunction with magnetic resonance imaging (MRI). The controller consists of two functional blocks: a host system and a remote system. The remote system resides inside the shielded room housing the magnet. The host, an IBM compatible personal computer, is located at the technician's console. Communication between these devices is implemented over a fiber optic RS-232 data link. This configuration allows experiments to be performed remotely by using a series of keyboard typed commands, by programming the host to send a series of commands, or by directly programming the remote system. As an example of its capabilities, the controller was used to tune and match arrays of receiver coils for localized imaging and to record the rectal temperature of a sedated rat during image acquisition. PMID- 1879852 TI - An active feedback system for isotonic studies of smooth muscle. AB - A feedback system used to perform isotonic studies of smooth muscle is presented. This system is capable of applying a constant force to muscle samples regardless of their contractile activities. The force applied to the tissue is controlled using a proportional integral control system that drives a linear motor. The device is integrated into a sucrose gap tissue bath apparatus where measurements of displacement and electrical activity are also possible. The frequency of canine colonic smooth-muscle electrical oscillations is positively related to applied force. PMID- 1879853 TI - An experimental study in electrical impedance tomography using backprojection reconstruction. AB - This paper reports on experiments designed to evaluate the performance of the equipotentials backprojection method under conditions modeling those of proposed applications of electrical impedance tomography. Small spherical targets were placed inside a saline-filled tank with dimensions similar to a human torso. Data were acquired with a computer-based instrument that applies current to pairs of electrodes located on two horizontal planes and records potential differences between electrodes of a third plane. The relative contrast produced by nonconducting spheres in a uniform saline background was measured on the reconstructed images and used to determine system sensitivity to target volume and to the radial and vertical positions of single spheres. Results show that for radial positions within a critical radius sensitivity is always maximum when the spheres center is on the recording plane and decreases gradually when the target is moved outside this plane. Localization of simple targets in 3-D, with data acquired from multiple recording planes, appears feasible. The results provide guidelines for the interpretation of images with complex 3-D conductivity distributions. PMID- 1879854 TI - Nonlinear receiver compression effects on the amplitude distribution of backscattered ultrasonic signals. AB - Nonlinear receiver compression effects on the amplitude distribution of backscattered ultrasonic signals are investigated by using digitized RF signals that have been compressed in a commercially made ultrasonic B-scan imaging instrument. Amplitude distributions of compressed RF and video signals were obtained from regions of B-scan images that correspond to approximately the same physical region in a random medium model with known backscatter amplitude characteristics. The amplitude distribution of the signal before compression was obtained by using a table constructed from measurements of the imaging instrument compression characteristics as a function of time gain compensation. While the results indicate the general form of the decompressed data agrees with single parameter model curves that are predicted by a widely employed Gaussian random process model, the signal-to-noise ratios of the decompressed envelope vary up to 20% from the 1.91 value predicted that model. This implies that effects such as nonlinearities, envelope smoothing, and noise which all may be present in varying degrees in practical ultrasonic imaging instrumentation can cause appreciable departures from theoretical data even under highly controlled conditions. PMID- 1879855 TI - A spherical-section ultrasound phased array applicator for deep localized hyperthermia. AB - Computer simulation shows that a new ultrasound phased-array with nonplanar geometry has considerable potential as an applicator for deep localized hyperthermia. The array provides precise control over the heating pattern in three dimensions. The array elements form a rectangular lattice on a section of a sphere. Therefore, the array has a natural focus at its geometric center when all its elements are driven in phase. When compared to a planar array with similar dimensions, the spherical-section array provides higher focal intensity gain which is useful for deep penetration and heat localization. Furthermore, the relative grating-lobe level (with respect to the focus) is lower for scanned foci synthesized with this array (compared to a planar array with equal center-to center spacing and number of elements). This could be the key to the realization of phased-array applicator systems with a realistic number of elements. The spherical-section array is simulated as a spot-scanning applicator and, using the pseudo-inverse pattern synthesis method, to directly synthesize heating patterns overlaying the tumor geometry. A combination of the above two methods can be used to achieve the desired heating pattern in the rapidly varying tumor environment. PMID- 1879856 TI - Control of specific absorption rate distribution using capacitive electrodes and inductive aperture-type applicators: implications for radiofrequency hyperthermia. AB - A method of controlling the specific absorption rate (SAR) distribution in radiofrequency hyperthermia is proposed. The superposition of the current density associated with capacitively coupled electrodes and that associated with H-field coupled inductive aperture-type applicators modifies the actual current distribution in the heating material. Using a two-dimensional finite element method, we have shown that "focusing" is possible such that the SAR at the center of a phantom can be adjusted to be approximately twice that in superficial regions, even though the wavelength is considerably greater than the dimensions of the phantom. PMID- 1879857 TI - Magnetocardiographic functional localization using current multipole models. AB - High-resolution magnetocardiographic mapping was applied to localize the ventricular preexcitation site in ten patients suffering form Wolff-Parkinson White syndrome. Three different source models were tested, consisting of the dipole and quadrupole moments in a general multipole expansion. Noninvasive localizations were performed by computations based on measured magnetic maps without a priori assumptions of the source location and without imposing any constraints. In all cases, the computed results were compared with invasive localization results obtained by catheter mapping technique. Preoperative catheterization localizes the atrial end of the accessory pathway, while our method localizes the ventricular preexcitation site. Of the models used, the average three-dimensional difference between the invasive localization results and the HR-MCG results was smallest 2.9 cm for the source model consisting of the magnetic dipole. The preexcitation site was very deep in all cases. The current dipole alone was inaccurate in estimating the source depth, but inclusion of the quadrupole moments improved the results. Two of the patients underwent surgery to interrupt the accessory pathway, which provided further validation for the noninvasive localizations. PMID- 1879858 TI - Magnetocardiographic functional localization using a current dipole in a realistic torso. AB - We describe a fast and numerically effective biomagnetic inverse solution using a moving dipole in a realistic homogeneous torso. We applied the localization model and high-resolution magnetocardiographic mapping to localize noninvasively the ventricular preexcitation site in ten patients suffering from Wolff-Parkinson White syndrome. In all cases, the computed localization results were compared to the results obtained by invasive catheter technique. Using a standard-size torso model in all cases, the average 3-D distance between the computed noninvasive locations and the invasively obtained results was 2.8 +/- 1.4 cm. When the torso was rescaled to better match the true shape of the subject in five cases, the 3-D average was improved to 2.2 +/- 1.0 cm. This accuracy is very satisfactory, suggesting that the method would be clinically useful. PMID- 1879859 TI - A quasi-power theorem for bulk conductors: comments on rheoencephalography. AB - A special case of Tellegen's theorem, the quasi-power theorem, can be readily developed for bulk conductors, and a bulk conductor analog of Cohn's theorem follows which allows prediction of sensitivity of impedance plethysmographic measurements to tissue impedance changes in a system of bulk conductors. An example addressing the effects of scalp and cranium on the inference of regional blood flow in brain tissue begs additional questions about the origins of the rheoencephalogram. PMID- 1879860 TI - Polarized light scattering of nucleosomes and polynucleosomes--in situ and in vitro studies. AB - Nucleosomes, chromatin and nuclei, extracted from rat hepatocytes, are studied by a new "in house" experimental configuration which measures circular intensity differential scattering (CIDS) and other elements of the polarized light scattering matrix. The Mueller matrix elements, S14 and S34, that are related to the geometric parameters of the superhelical arrangement of polynucleosomes point to the existence of a quaternary structure at low ionic strength for chromatin prepared by the cold-water method, which is lost by shearing, and is not found in the soluble chromatin prepared through the nuclease method. Only salt addition to a final concentration of 5 mM MgCl2, 150 mM NaCl and 10 mM Tris HCl (pH 7) yields a sizeable (S14 + S34) signal in the latter chromatin, which is however still different from the corresponding signal of native nuclei and of "cold-water" chromatin. Comfortingly, the (S14 + S34) signal from isolated nucleosomes is consistently very low (nearly zero) as predicted by multiple dipole simulation within the framework of classical electrodynamics. Results are discussed in terms of the topological constraints present in the native long chromatin fiber, which are lost after limited nuclease digestion and after shearing. PMID- 1879861 TI - Perceived locus and intensity of electrocutaneous stimulation. AB - Two experiments investigated perceived locus and intensity for electrocutaneous stimulation. In Experiment 1, 21 subjects reported the perceived locus for various combinations of four electrode sites, two current directions, two pulse characteristics (single versus multiple), and two sensation levels (detection versus pain). In Experiment 2, 16 subjects reported the perceived locus and intensity for a wide range of current levels and two polarity conditions. The main results were 1) sensations were likely to be perceived under the cathode at detection levels, but under both electrodes at intense levels; 2) the "cathode" localization was gradually supplanted by "both" ("anode" and "cathode") localization with increasing current; 3) subjective intensity under the cathode was greater than that under the anode; 4) the effects of cathode position on perceived locus were found for only some pairs of electrodes. These results challenge the simple hypothesis that electrical stimulation of the skin through paired electrodes is perceived under the cathode. PMID- 1879862 TI - Feedback control of coronal plane hip angle in paraplegic subjects using functional neuromuscular stimulation. AB - This paper reports on an investigation of feedback control of coronal plane posture in paraplegic subjects who stand using functional neuromuscular stimulation (FNS). A feedback control system directed at regulating coronal plane hip angle in neutral position was designed, implemented, and evaluated in two paraplegic subjects. The control system included sensor mounting and signal processing techniques, a two-stage feedback controller, stimulation hardware, and a set of percutaneous intramuscular electrodes. The feedback controller consisted of two-stages in cascade: a modified discrete-time proportional-integral derivative (PID) stage and a nonlinear single-input, multiple-output stage to determine the stimulation to be sent to several muscles. The focus of this work was on evaluating the performance of the feedback controller by comparing the response of the feedback-controlled system to that of an open-loop stimulation system. In an evaluation based on temporal response characteristics the controlled system exhibited a 41% reduction in root-mean-squared (rms) error (where error is defined as the deviation from the desired angle), a 52% reduction in steady-state error, and a 22% reduction in hip compliance. In addition, the feedback-controlled system exhibited significant reductions in variability of these measures on several days. These results demonstrate the ability of the feedback controller to improve the temporal response characteristics of the FNS control system. PMID- 1879863 TI - Bayesian statistics as applied to hypertension diagnosis. AB - This paper deals with the following hypertension diagnoses: essential hypertension and five types of secondary hypertension: fibrodysplasic renal artery stenosis, atheromatous renal artery stenosis, Conn's syndrome, renal cystic disease, and pheochromocytoma. Only blood pressures, general information and general biochemical data are taken into account. Nineteen items were finally selected, by statistical investigation of experimental data, as being both discriminative and independent. The marginal density distributions of every item, and then joint density distribution functions were determined within six types of hypertension. The frequency of a given hypertension type within the hypertensive patients was used as prior probability of this state. The loss matrix was established by medical arguments. The expected loss corresponding to six possible decisions could thus be calculated for all cases. Both the ratio of secondary hypertensions that could be inferred from our set of data (not including the results of complementary tests) and that of correct "essential" hypertension diagnosis proved to be satisfactory. PMID- 1879864 TI - In-line lead connector for use with implanted neuroprosthesis. AB - The design, implementation, and preliminary testing of an implantable in-line connector for individual lead-wires is presented. The connector provides for replacement of implanted components without disturbing other elements of the implanted system. Its flexibility and size makes it suitable for implantation in neuromuscular applications. PMID- 1879865 TI - A microprocessor-based data-acquisition system for measuring plantar pressures from ambulatory subjects. AB - We have developed a portable microprocessor-based data-acquisition system to measure discrete plantar pressures within the shoe from ambulatory subjects. The system offers improved accuracy, repeatability, portability, and flexibility not available in current commercial systems. It consists of 14 conductive polymer pressure sensors, 14 analog amplifiers, an 8-bit analog-to-digital converter, a microprocessor, 120 kbytes of memory space, and a parallel I/O interface. Seven pressure sensors are embedded within each insole and located at the posterior heel, anterior heel, the four metatarsal heads, and hallux of each foot. The system is capable of continuously sampling 14 channels of pressure data for 7 min at a 20-Hz sample rate. The recorded data are downloaded into a microcomputer for further processing, analysis, and display. Foot pressures have been acquired from a sensate subject during multiple walking trials. PMID- 1879866 TI - A layer-recursive formula for the medium filter for volume conductor problems in radially symmetric layered media. AB - Simplified algorithms for the computation of the filter coefficients used in solutions of the forward and inverse volume conductor problems in a multilayered cylindrical geometry are derived. The new algorithms are layer-recursive, as opposed to previous algorithms which were specific for the structure studied. The new algorithms not only eliminate the need to derive algebraically cumbersome filter expressions, but also speed up their numerical evaluation. PMID- 1879867 TI - Isolation of a tripeptide showing weak acetylthiocholine hydrolysing activity from a soluble form of monkey basal ganglia acetylcholinesterase by limited trypsin digestion. AB - Acetylcholinesterase was purified from the soluble supernatant of monkey (Macaca radiata) brain basal ganglia by a three-step affinity purification procedure. The purified enzyme showed two major protein bands corresponding to molecular weights of approximately 65 kDa and approximately 58 kDa which could be labelled by [3H]diisopropylfluorophosphate. When the purified enzyme was subjected to limited trypsin digestion followed by gel filtration on Sephadex G-75 or Sephadex G-25 column, a peptide fragment of molecular weight approximately 300 Da having a weak acetylthiocholine hydrolysing activity was isolated. The amino acid sequence analysis of this peptide showed a sequence of Gly-Pro-Ser. When the [3H]DFP labelled enzyme was subjected to limited trypsin digestion and Sephadex G-75 column chromatography, a labelled peptide corresponding to approximately 430 Da was isolated. The kinetics, inhibition characteristics and binding characteristics to lectins of this peptide were compared with the parent enzyme. A synthetic peptide of sequence Gly-Pro-Ser was also found to exhibit acetylthiocholine hydrolysing activity. The kinetics and inhibition characteristics of the synthetic peptide were similar to those of the peptide derived from the purified acetylcholinesterase, except that the synthetic peptide was more specific towards acetylthiocholine than butyrylthiocholine. The specific activity (units/mg) of the synthetic peptide was about 123700 times less than that of the purified AChE. PMID- 1879869 TI - Protein adsorption at solid-liquid interfaces: Part II--Adsorption from binary protein mixture. AB - Extent of adsorption of proteins at alumina-water interface from solutions containing binary mixture of beta-lactoglobulin and bovine serum albumin (BSA), beta-lactoglobulin and gelatin, and gelatin and bovine serum albumin has been estimated as functions of protein concentrations at varying pH, ionic strength, temperature and weight fraction ratios of protein mixture. The extent of adsorption (gamma lacw) of lactoglobulin in the presence of BSA increases with increase of protein concentration (Clac) until it reaches a maximum but a fixed value gamma lacw(m). Extent of adsorption gamma serw also initially increases with increase of protein concentrations until it reaches maximum value gamma serw(m). Beyond these protein concentrations, adsorbed BSA is gradually desorbed due to the preferential adsorption of lactoglobulin from the protein mixture. In many systems, gamma serw at high protein concentrations even becomes negative due to the strong competition of BSA and water for binding to the surface sites in the presence of lactoglobulin. For lactoglobulin-gelatin mixtures, adsorption of both proteins is enhanced as protein concentration is increased until limiting values for adsorption are reached. Beyond the limiting value, lactoglobulin is further accumulated at the interface without limit when protein concentration is high. For gelatin-albumin mixtures, extent of gelatin adsorption increases with increase in the adsorption of BSA. The limit for saturation of adsorption for gelatin is not reached for many systems. At acid pH, adsorbed BSA appears to be desorbed from the surface in the presence of gelatin. From the results thus obtained the role of electrostatic and hydrophobic effects in controlling the adsorption process has been analysed. PMID- 1879868 TI - Protein adsorption at solid-liquid interfaces: Part I--Affinities of proteins for alumina surface. AB - Extent of adsorption (gamma pw) of bovine serum albumin, beta-lactoglobulin, gelatin and myosin at the alumina-water interface has been measured as function of protein concentration (Cp) at several temperatures, pH, and ionic strengths of the medium. gamma pw for proteins in most cases increases with increase of protein concentration but it attains maximum value gamma pw(m) when Cp is high. Values of maximum adsorption have been examined in terms of molecular orientation, molecular size and shape and unfolding of the packed proteins at the interface. In few cases, gamma pw increases with increase of Cp without reaching a real state of saturation as a result of aggregation of molecules or extensive unfolding of the protein at the interface. In the case of beta-lactoglobulin at pH 5.2 and ionic strength 0.05, gamma pw in high concentration region decreases to zero value when Cp increases. For myosin at 45 degrees C and pH 6.4, and also at 27 degrees and pH 7.8, the values of gamma pw are all negative and these negative values increase with increase of Cp. All these results have been explained in terms of significant competitions of water and protein for binding to the surface sites of the powdered alumina. Adsorption of myosin has also been found to be affected in the presence of NaCl, KCl, CaCl2, KI, Na2SO4, LiCl and urea. The relative affinities of the adsorption of various proteins for the surface of alumina at different physical conditions of the system have been compared in terms of maximum values of adsorption attained when gamma pw is varied with Cp. The affinities are shown to be compared more precisely in terms of the standard free energy decrease for the saturation of the surface by protein as a result of the change in its concentration from zero to unity in the mole fraction scale. PMID- 1879870 TI - Depolarization of synaptosomal membranes: a study of mechanism by which rhodamine 6G measures membrane potential. AB - The fluorescence intensity of Rhodamine 6G in synaptosomal suspensions has been measured to monitor the membrane potential changes in pre-synaptic nerve terminals. The fluorescence response of the dye was seen to be a function of potential-dependent partitioning of dye molecules between the synaptosomes and the extracellular medium. Binding of dye molecules to the hydrophobic regions of membranes results in the quenching of fluorescence. Upon depolarization of the synaptosomal membrane, the dye molecules are released from the cells. The effect of changing extracellular ionic composition was also studied. The membrane potential increased linearly with log of [K]0. The resting membrane potential in buffer containing 5 mM K+ was calculated to be -60 mV. Raising the extracellular Ca2+ and Mg2+ from 1.2 mM to 10 mM did not change the membrane potential. Ca2+ ionophore A23187, in the presence of Ca2+ was found to depolarize the membranes. PMID- 1879871 TI - Transformation of sitosterol to androsta-1, 4-diene-3, 17-dione by immobilized Mycobacterium cells. AB - Transformation of sitosterol to androsta-1, 4-diene-3, 17-dione was studied with Mycobacterium cells entrapped in various polymeric matrices. Of the three supports viz. alginate, carageenan, agarose and polyacrylamide, studied, the polyacrylamide immobilized cells showed optimum catalytic stability and reusability. PMID- 1879872 TI - Some physicochemical properties of human milk bile-salt activated lipase. AB - Influence of pH, deoxycholate and denaturing reagents on human milk bile-salt activated lipase (EC 3.1.1.3) has been studied. It appears that pH between 5.0 8.0 has no significant effect on the secondary structure of this lipase, but its higher order structures are affected. Lipase-dependent 8-anilino-1-naphthalene sulphonate fluorescence has revealed that the deoxycholate activated form of lipase has a surface rich in hydrophobic amino acid residues. Circular dichroism and second derivative electronic absorption spectroscopic observations have also provided an evidence for deoxycholate-induced alterations in the surface conformation of this lipase. PMID- 1879873 TI - Methylation, acetylation and phosphorylation of the bases of DNA of young and old rats. AB - The possibility of methylation, acetylation and phosphorylation of the bases of DNA has been studied in vitro by incubating nuclei of the liver and cerebral hemisphere of young (18 wk) and old (120 wk) rats with radioactive donors, [3H]S approximately adenosyl methylmethionine, [3H]-acetyl approximately CoA and [32P] gamma-ATP for methylation, acetylation and phosphorylation of the bases, respectively. Nuclei were also incubated with S approximately adenosyl homocysteine to inhibit methylation with sodium butyrate to stimulate acetylation and with alkaline phosphatase to remove phosphate groups incorporated into the bases. DNA was then extensively purified and incorporation of each type of label was estimated. The data show that both methylation and acetylation of DNA of old rats were significantly higher than those of young rats, and phosphorylation is lower in old rats. Such modifications may prevent base pairing between the two strands of DNA, alter its conformation and binding of trans-acting factors at specific sites, and thereby alter gene expression. PMID- 1879874 TI - Alterations in dendritic cell phenotype and function associated with immunoenhancing effects of a subcutaneously administered cyclophosphamide derivative. AB - A single systemic dose of cyclophosphamide (CY) has been shown to enhance cellular immunity in a variety of antigen models. The immunoenhancing effects of CY have been attributed to its ability to selectively abrogate suppressor cell function. Previous studies from our group have demonstrated that local administration of distinct cytostatic drugs at the sensitization site can induce a similar enhancement of delayed-type hypersensitivity as systemic CY, with the obvious advantage of avoiding systemic side-effects. In the present study we investigated the effects of local administration of an optimally immunopotentiating dose of the active CY-derivative Z 7557 and, in selected experiments, of etoposide (VP-16) and systemic CY on mononuclear cells in draining lymph nodes. Whereas CY caused a long-lasting and marked depletion of B cell areas, locally administered Z 7557 and VP-16 relatively spared B cells and even induced an increase in B- and T-cell numbers in (keyhole limpet haemocyanin ) sensitized mice. At Day 4 the CD4/CD8 ratio was slightly reduced in drug treated mice. Interestingly, drug treatment reduced the proportion of interdigitating cells staining with the monoclonal antibodies NLDC-145 and MIDC 8. Upon isolation, dendritic cells (DC) from sensitized, Z 7557-treated mice showed longer dendritic protrusions and an enhanced accessory cell function compared to DC from saline-treated controls. These findings suggest that immunoenhancing effects of cytostatic drugs may occur via an effect on DC. PMID- 1879875 TI - C3- and T-cell-dependent adjuvant activity of in vivo formed immune complexes. AB - The effects of polyclonal antibodies to mouse serum components on the primary humoral immune response of mice in vivo were studied. It was observed that rabbit IgG to complement component C3 and albumin and mouse IgG to C5, but also heat aggregated non-immune rabbit IgG, enhanced the agglutinating antibody response to sheep erythrocytes (SRBC). Since the increase in response was only observed when antigen and antibodies were administered via the same route (i.p.), immunological adjuvant activity was implicated. Ineffectiveness of anti-C5 IgG in C5-deficient mice indicated that the antibody-induced adjuvant activity is mediated by in vivo formed immune complexes (IC). The adjuvant activity of IC was reduced by selective C3-depletion of animals, pointing to a requirement of C3. The effect of variations in other parameters was studied with anti-C3 and anti-C5 IgG as immunoadjuvant. The immunostimulatory effect was most pronounced when the antibodies were administered simultaneously with or shortly before antigen. Treatment of animals with antibodies one or two days before antigen, however, resulted in a suppression of the response. The response to thymus-independent antigens was not enhanced by anti-C3 nor by anti-C5 IgG. Optimal adjuvant activity of anti-C3 IgG was observed at low antigen doses. Nude mice were insensitive to the immunopotentiating effect of anti-C3 and so was the F1 progeny of BALB/c male and CBA/N female mice expressing a B-cell maturation defect. C5 deficiency and lipopolysaccharide (LPS) non-responsiveness did not affect the adjuvant activity of in vivo formed C3-anti-C3 IC. PMID- 1879876 TI - Iccosomes and the secondary antibody response. AB - Iccosomes derived from follicular dendritic cells (FDC) are believed to play an important role in dispersion of antigen necessary for induction of anamnestic responses. Because FDC are aberrant and iccosome release has not been observed in aged mice, we hypothesized that these animals would be impaired in their ability to mount anamnestic responses. To test this, anamnestic responses were compared in aged and control mice. To ensure the presence of functional lymphocytes, some aged mice were reconstituted with T- and B-memory cells obtained from control mice. Anamnestic responses in aged mice were markedly depressed even when given functional memory cells. To more directly relate the impaired antibody response of aged mice to FDC function, antigen-bearing FDC from either aged or control mice were incubated with T- and B-memory cells from control mice to induce an anamnestic response. Antigen retained by FDC from aged mice was much less immunogenic than antigen retained by FDC from control mice. Since iccosome formation does not appear in aged mice, iccosome-like fragments were generated by sonicating FDC from aged mice and tested for their ability to induce an anamnestic response. This procedure restored the ability of antigen retained on FDC from aged mice to induce a normal anamnestic response. These data support the concept that the inability to form and disperse iccosomes contributes to the impaired ability of aged mice to mount anamnestic antibody responses and provides further support for the role of iccosomes in anamnestic responses. PMID- 1879877 TI - Monoclonal antibody-directed targeting of fluorescent polystyrene microspheres to Peyer's patch M cells. AB - The ability to deliver particulates to Peyer's patch M cells for uptake into gut associated lymphoid tissue was examined by administering simultaneously fluorescent green and red polystyrene microspheres into NZW rabbit intestinal loops containing Peyer's patches. Whereas green and red microspheres were taken up by M cells at equivalent concentrations (120 +/- 17 versus 125 +/- 18/mm length of dome), particles conjugated to the anti-M-cell monoclonal antibody 5B11 (IgM, kappa) were internalized by M cells 3-3.5 times more efficiently than conjugates displaying IgM of unrelated specificity (TEPC 183) or native particles of the reciprocal colour inoculated into the same loop at a comparable load. The microspheres formed a concentration gradient from lumen to subepithelial dome, and localized on M-cell apical membranes, M-cell pockets, and subepithelial domes. The transport rate across M cells of 5B11 or TEPC 183 conjugates was similar to that of untreated microspheres. These observations show that intestinal uptake into Peyer's patches can be upregulated by targeting M-cell luminal membrane structures. PMID- 1879878 TI - Lymph-borne (veiled) dendritic cells can acquire and present intestinally administered antigens. AB - To investigate the ability of lymph-borne (veiled) dendritic cells (LDC) to acquire and present antigens in vivo, mesenteric lymphadenectomized rats were injected intra-intestinally with antigen and LDC were then purified from thoracic duct lymph. When used as antigen presenting cells with primed spleen cells as responders, the LDC could stimulate antigen-specific proliferation of the responder cells in the absence of exogenous added antigen. As little as 10 mg of ovalbumin (OVA) or horseradish peroxidase (HRP) injected into the ileum and jejunum could sensitize LDC for presentation. LDC acquired antigen within 8 hr of its injection but cells collected more than 24 hr after injection were unable to stimulate a response. Non-dendritic cells (NDC) in the thoracic duct lymph, such as B cells, were unable to present antigen either following intraintestinal injection or after in vitro pulsing. The antigen-specific response was blocked by antibodies to CD4 and major histocompatibility complex (MHC) class II and was totally dependent on the presence of CD4+ cells in the responding population. These studies show that dendritic cells can acquire antigens in vivo and provide a novel approach to the study of intestinal immune responses and oral tolerance. PMID- 1879879 TI - Interleukin-2-induced DNA synthesis and immunoglobulin secretion by resting human tonsillar B cells: effects of protein kinase C activation. AB - Responses to interleukin-2 (IL-2) of high-density human tonsillar B lymphocytes were examined in 20 microliters hanging drop microcultures. DNA synthesis and secretion of IgM and IgG were induced by IL-2 alone. Activation of calcium dependent protein kinase C (PKC) with phorbol 12,13-dibutyrate and ionomycin increased IL-2 driven DNA synthesis yet reduced IL-2 driven secretion of IgM and IgG. Forskolin, which increases cAMP, had no effect on the responses to IL-2. Intrinsic IL-6 played no role in IL-2-induced DNA synthesis but was partially responsible for the secretion of immunoglobulin. These data show that pre activation of the high-density human tonsillar B lymphocyte is not a prerequisite for IL-2-driven responses. They also show an asymmetry between the growth and differentiation induced by IL-2. This is reflected by opposite modulation on activation of PKC and by the role of the autocrine factor, IL-6. PMID- 1879880 TI - Human T-cell responses to ragweed allergens: Amb V homologues. AB - Specific IgE and IgG responses to highly purified Ambrosia (ragweed) allergens, Amb a V, Amb t V and Amb p V from the artemisiifolia (short), trifida (giant) and psilostachya (western) species are strongly associated with HLA-DR2 and Dw2 (DR2.2) in allergic Caucasoid individuals. To investigate the molecular basis of these HLA associations, we examined the human T-cell responses to these Amb V homologues using three Amb a V-specific, DR alpha beta I 2.2-restricted T-cell clones from an atopic patient. We first examined the cross-reactivity of Amb a V specific T-cell clones upon challenge with the Amb a V homologues, Amb t V and Amb p V, in the presence of autologous antigen-presenting cells (APC). Neither Amb t V nor Amb p V was able to stimulate the T-cell clones directly. However, both Amb t V and Amb p V specifically blocked, in a dose-dependent fashion, the ability of APC to present Amb a V to all three T-cell clones. Taken together, these results suggest that Amb t V and Amb p V possess distinct T-cell epitopes, but that all Amb V homologues share similar or identical regions (agretopes) interacting with the DR alpha beta I 2.2 (DR alpha beta I 1501) heterodimer. The agretope was potentially localized to a 14-residue C-terminal Amb a V peptide (with Ala-Cys substitutions), which was able to block presentation of native Amb a V by the APC to the T-cell clones. PMID- 1879882 TI - Effect of antibiotics on polymorphonuclear function in iron deficiency anaemia patients & normal volunteers. AB - The effect of erythromycin and gentamicin on polymorphonuclear leukocyte (PMN) functions was assessed in normal individuals and in patients with iron deficiency anaemia (IDA) before and after treatment with iron. The PMN phagocytic function was investigated by the standard method. Erythromycin in vivo significantly increased the PMN phagocytic function from 44.18 +/- 2.08 to 57.0 +/- 1.5 at 8 h and the bactericidal activity from 48.33 +/- 1.97 to 56.7 +/- 0.89 at 8 h in the normal adult male volunteers. A significant increase in phagocytic and bactericidal function of PMNs from IDA patients was also observed after in vivo administration of erythromycin. Gentamicin in vitro reduced the bactericidal activity of PMN from normal volunteers (P less than 0.05) but increased the PMN phagocytic activity in normal volunteers and IDA patients. PMID- 1879881 TI - Increase in the intracellular free calcium concentration is not an obligatory early event in lipopeptide-induced B-cell activation. AB - We recently showed that synthetic lipopeptides, analogues of the N-terminal region of bacterial lipoprotein, induce DNA synthesis in B lymphocytes in the absence of enhanced phosphatidylinositol 4,5-bisphosphate hydrolysis and protein kinase C translocation. Here we demonstrate that lipopeptides are capable of inducing enhanced expression of MHC class II molecules and early increases in the intracellular free calcium concentration ([Ca2+]i) in B cells. However, they do not effect T cells. The increase in [Ca2+]i seen in B cells is due primarily to Ca2+ release from intracellular stores. Since lipopeptides differ in their capability to induce early increases in [Ca2+]i and since the calcium response does not correlate with the ability of lipopeptides to induce proliferation and expression of MHC class II molecules, we suggest that this biochemical event may not be essential for lipopeptide-mediated B-cell activation. PMID- 1879883 TI - Influence of noise spectra on auditory frequencies & degree of temporary threshold shift. AB - Influence of noise spectra on auditory frequencies of 131 audiometrically normal human volunteers was assessed. Each subject was exposed to four different types of noise on different days for a period of 30 min. Noises utilized in this study were broadband noise (100 dBA), broadband noise (BBN) mixed independently with tones of 0.5, 1.2 and 4 kHz at three intensity levels (85, 95 and 105 dBA) and noises of different bandwidths (100 dBA) around the above tones as centre frequencies. BBN produced maximum TTS2 at 4 kHz (21.42 +/- 0.61 to 26.15 +/- 1.00 dB), while concentration of sound energy around these tones, affected hearing at one-half octave above the point of concentration of sound energy. TTS2 produced by 4 kHz tonal component of 95 and 105 dBA and 2 kHz of 105 dBA were significantly higher than the one produced by BBN at 4 kHz. The single tones of 2 and 4 kHz and noise of 1/3rd octave bandwidth (cf 4 kHz) produced TTS2s which were significantly higher as compared to that of BBN at 4 kHz. At the same centre frequency, noise concentrated in thinner bands was more injurious than that in the thicker bands. Lower frequencies of hearing appears to be more resistant to noise as for the same sound pressure level the TTS2 observed in low frequencies was less as compared to higher frequencies. PMID- 1879884 TI - DDT levels in human body fat & milk samples from Delhi. AB - A study of 45 human fat samples from autopsy and surgery specimens from Delhi showed a mean total DDT level of 6.37 micrograms/g (SE +/- 0.36; range 3.34-9.12 micrograms/g). While these values compare well with those reported from India and abroad, they are much lower than those obtained from other areas of Delhi, confirming wide variation in the quantity of DDT sprayed in different pockets of this city. Twenty one human milk samples from Delhi showed a mean total DDT level of 0.144 ppm (micrograms/ml). Thus, many infants in Delhi appear to be consuming 3 to 5 times the permissible 5 micrograms/kg/day quantity of DDT. This study too indicates the need of continuous monitoring of DDT and other insecticides commonly used in India. PMID- 1879885 TI - Effect of instant preparation of betel nut (pan masala) on the oral mucosa of albino rats. AB - Paste made out of an instant betel nut preparation was painted into the oral cavity of 21 albino rats on alternate days for a period of six months. Biopsies were taken from the oral mucosa at the beginning of the study and every two months there after and compared histopathologically with those obtained from a control group of 14 albino rats. Mild to moderate loss of nuclear polarity and increase in keratoses, parakeratoses, inflammatory cell infiltration and vascularity were noted when compared to the control group. The increase in mitotic figures was statistically insignificant and no definite changes in pigmentation or atypical cells were seen. These findings suggest the possibility of mild leukoplakia. Submucosal collagen increased steeply and steadily throughout the study period and at the end of six months, 88.23 per cent of biopsies showed thickened and condensed sub-mucosal collagen, indicating submucous fibrosis. PMID- 1879886 TI - Microalbuminuria in NIDDM patients in south India. AB - Urinary albumin excretion (UAE) was estimated by radioimmunoassay in 316 non insulin dependent diabetic patients (NIDDM), with diabetes for 10 or more years and proteinuria less than 150 mg/24 h. Albuminuria was determined in 24 h collection of urine in 259 patients but in the other 57, a random sample was used. The mean UAE was 23 +/- 45.3 (SD) micrograms/mg creatinine in the patients against 4.4 +/- 2.7 micrograms/mg in the controls (30). Ninety patients (28.5%) had microalbuminuria i.e., the UAE exceeded, 20 micrograms/mg creatinine. A higher percentage (31.7%) of men had microalbuminuria than women (23.6%). The presence of microalbuminuria was similar in the insulin-treated and in oral drug treated patients (29.6% and 26.5% respectively). Stepwise multiple regression analysis using albumin/creatinine ratio as the dependent variable showed that factors such as blood pressure, blood glucose, HbA1, body mass index, sex, age, duration of diabetes and the association of vascular complications of diabetes did not have significant correlation to microalbuminuria. Creatinine clearance showed a significant inverse correlation to the albumin/creatinine ratio. Although the prevalence of microalbuminuria in NIDDM in this study is not significantly different from those reported from other countries, the morbidity index due to kidney disease could be high due to the large absolute number involved in our country. This underscores the need for early detection of the disease and institution of preventive measures to arrest its progression. PMID- 1879887 TI - Epidermal calmodulin levels in psoriasis before & after therapy. AB - Epidermal calmodulin (CaM) levels were measured in the involved and uninvolved skin in 26 psoriasis patients before and after treatment either with dithranol topically or methotrexate orally. The mean epidermal calmodulin levels (+/- SD) in the involved and uninvolved psoriatic skin before treatment were 21.99 +/- 10.22 and 11.97 +/- 3.50 in the patients to be treated with short contact dithranol therapy (SCDT) while it was 19.46 +/- 8.13 and 11.27 +/- 7.23 in the patients to be treated with systemic methotrexate. Clearance of psoriatic lesions was associated with a significant fall (P less than 0.05) in epidermal calmodulin, activity irrespective of the treatment modality used. Also, there was a significant reduction (P less than 0.05) in the calmodulin levels in the epidermis of uninvolved skin following successful treatment. PMID- 1879888 TI - Effect of skim milk on cholesterol induced blood platelet hyperaggregability in rabbit. AB - Effect of high cholesterol diet on blood platelet aggregation, and the influence of skim milk on cholesterol induced platelet hyperaggregability were studied in rabbits. The level of aggregated platelets (AP) increased to 19900/mm3 and that of plasma cholesterol to 1605mg/dl, while platelet aggregate ratio (PAR) decreased to 0.32 in rabbits fed high cholesterol diet (0.5% cholesterol) for 12 wk. The levels of AP (12500/mm3) and plasma cholesterol (1196mg/dl) were lower, and the PAR (0.46) was higher in rabbits which received the cholesterol diet supplemented with 16 per cent skim milk powder. In the second experiment, hypercholesterolaemia and platelet aggregation were induced in rabbits by high cholesterol diet given for 6 wk. The animals then received cholesterol-free diets for 8 wk, one group receiving the diet supplemented with 16 per cent skim milk powder and the other without milk served as the control group. The mean PAR in the milk powder supplemented group was restored to normal at 6 wk, while in the control group the level continued to be lower even up to 8 wk. The results thus demonstrate that the milk can prevent the process of cholesterol induced platelet aggregation. PMID- 1879889 TI - Effect of coconut oil & safflower oil on lipids in isoproterenol induced myocardial infarction in rats. AB - Effect of feeding safflower oil and coconut oil in experimental myocardial infarction induced by isoproterenol in rats was studied. Based on the survival rate and histopathological examination, safflower oil was found to offer better protection than coconut oil. Serum GOT levels also confirmed the protective activity of safflower oil. The concentrations of cholesterol and triglycerides in the heart and aorta were lower in the safflower oil fed group, while the level of phospholipids was higher. PMID- 1879890 TI - Central auditory toxicity of sisomicin in guineapigs. AB - The central auditory toxicity of sisomicin was studied in guineapigs administered sisomicin (135 mg/kg body weight) sc for 10 days. Total lipids, phospholipids and cholesterol were estimated in the pons, inferior colliculus, medial geniculate body and auditory cortex. While the total lipids were increased in a non preferential manner in all the regions studied, phospholipids and cholesterol levels registered no change. This study suggests the possible central auditory toxicity following sisomicin administration. PMID- 1879891 TI - Multicentric study on genetic causes of mental retardation in India. ICMR Collaborating Centres & Central Co-ordinating Unit. AB - A study on 1314 children with mental retardation (MR) without an obvious environmental cause was carried out at Bangalore, Bombay, Delhi and Lucknow to determine the extent and pattern of genetic causes of mental retardation in different parts of India. In all, 42.3 per cent patients had mild, 25.3 per cent moderate, 19.2 per cent severe and 13.1 per cent profound mental retardation. Among 1314 patients, the chromosomal anomalies were found in 23.7 per cent, metabolic defects in 5.0 per cent and an identificable genetic syndrome in 11.6 per cent of the patients. In the remaining 59.7 per cent patients, no known genetic cause could be identified. However, 66.5 per cent of these patients had one or more of the following conditions: (i) congenital malformation with or without neurological deficit, (ii) history of consanguinity, (iii) positive family history of mental retardation or (iv) a positive screening test but without a confirmed diagnosis of metabolic defect (suggesting that there may be additional unidentified genetic causes of mental retardation). PMID- 1879892 TI - Learning disability in rural primary school children. AB - In rural primary school children observed for two years, 12.97 per cent of those having IQ greater than or equal to 90 were found to have poor achievement in arithmetic test and teacher's assessment. These learning disabled children had impaired perceptual maturity and conceptual grasp as observed on MISIC (Indian modification of WISC), Bender Gestalt test and Piaget's test. On WISC Bannatyne categories learning disabled children scored highest in verbal conceptualization (similarities, vocabulary, comprehension), followed by spatial (picture completion, object assembly, block design) and sequencing (arithmetic, digit span, coding) abilities. These children on Bender Gestalt test made more errors particularly distortions (distortion of parts, incorrect number of dots, shape of design lost etc). They also showed delayed development on Piagetian tasks class inclusion, conservation (for length, substance, liquid and number) ordinal relation and one to one correspondence. These observations indicate impaired perceptual maturity, conception and information processing deficit. PMID- 1879893 TI - Occurrence of systemic autoimmune disorders & autoantibodies in house-hold contacts of patients with systemic lupus erythematosus. AB - Household contacts of 22 randomly selected patients with systemic lupus erythematosus (SLE) were screened for autoimmune diseases and autoantibodies. Thirty nine consanguineous and 17 nonconsanguineous household contacts were studied. In the first group symptomatic SLE was seen in 5 per cent, rheumatoid arthritis in 2.5 per cent, antinuclear antibody (ANA) in 10 per cent and rheumatoid factor (RF) in 5 per cent while anti-dsDNA, anti-nRNP and anti-Sm antibodies were not detected in any individual. The second group showed total absence of any marker of autoimmunity. In normal controls only RF was detected in 3 per cent. The occurrence of markers of autoimmunity only in consanguineous household contacts of patients with SLE further confirms the recognised role of genetic factors in the etiology of SLE. PMID- 1879894 TI - Child survival and child health development activities for the Eighth Five Year Plan in India (1990-1995)--Part II. Planning Commission, Government of India. PMID- 1879895 TI - On health and healing: community health care in India. PMID- 1879896 TI - Improving neonatal care in India: is there a place for developing neonatal intensive care units. PMID- 1879897 TI - Vitamin A during pregnancy in India: how much is safe for the fetus? PMID- 1879898 TI - Evolving concepts in the pre-operative management and surgical treatment of craniosynostosis. PMID- 1879900 TI - Epidemiology of diarrhea and its implications for providing services. AB - This study was conducted in children under the age of four years for a period of one year. By domiciliary visits the diarrheal episodes were recorded, analysed and presented. The findings are based on the diarrheal experience of 4860 children. The attack rate was 2.6/child/year. Family with more than one child had more attacks. Mean duration was 5.76 days and 11.2% had lasted more than 7 days. All the age groups are similarly affected. 75.6% were just plain loose motions and only 4.9% had blood, mucus or fever associated with loose motions. Case fatality was 0.6%. Attack rate was more in June-August and December-February than the other quarters. 42.2% were shown to R.M.P.s. and 33.6% consulted friends or relatives. More than 2/3 gave mainly home made ORS. 69.9% restricted food during attack. PMID- 1879899 TI - An approach to respiratory distress and central nervous system emergencies. PMID- 1879901 TI - Growth performance of Bangladeshi affluent school children (5-14 years). AB - A cross sectional anthropometric survey of 2045 healthy children (5-14 years) of affluent society of Dhaka City was done with the aim to compare their growth with the National Centre for Health Statistics (NCHS) standard. It was found that both weight and height of boys and girls of the studied children fall between 25th to 50th percentile of NCHS standard. In case of boys, body weight deviates below 25th percentile after 12 years whereas mean height is nearly parallel to 50th percentile up to 14 years. In case of girls, the pattern of growth is same except the fall below 25th percentile at the age of 8 and 9 years and the height remains above 25th percentile up to 12 years. It can be concluded that mean growth of affluent Bangladeshi school children is comparable to NCHS standard with minor variations. PMID- 1879902 TI - Serum levels of gentamicin at peak and trough in neonates and infants. AB - The peak and the trough levels of serum gentamicin were determined in 50 cases of neonates and infants by microbiological assay method. The peak levels in the neonates and the infants were 5.98 +/- 0.48 and 4.63 +/- 0.31 mcg/ml respectively. The trough levels in the corresponding group were 1.06 +/- 0.19 and 0.94 +/- 0.23 mcg/ml. The mean values of the peak and trough levels of the antibiotic were 5.57 and 1.02 mcg/ml respectively. It was observed that there was a significant lower peak concentration in the infants than in the neonates. A significantly higher peak concentration of gentamicin was observed in babies aged under 7 days than in those above 7 days. The route of administration (between I/M and I/V) did not seem to have any effect on the peak and trough levels of the antibiotics. PMID- 1879904 TI - Residual poliomyelitis of lower limb-pattern and deformities. AB - The pattern of muscle paralysis and paresis in the lower limbs has been studied in 1356 children with 1800 poliomyelitic limbs, revealed that more than two-third (68 = 55%) muscles were affected, with the ratio of paresis and paralysed muscles were 1.89:1.00. The muscles most frequently affected were tibialis anterior (1516), quadriceps (1465) and tibialis posterior (1435) while tibialis anterior (1070), tibialis posterior (820) and quadriceps (766) were most commonly paralysed in descending order. The tibialis anterior which leads in paralysis group, has come last in order of frequency of paresis. The highest segmental incidence of affection of muscles found in second to fourth lumbar segments while muscle paralysis is found in fourth lumbar spinal segment. The commonest deformities encountered in residual poliomyelitis are flexion-abduction contracture hip, flexion contracture knee and valgus deformity foot. PMID- 1879903 TI - Detection of low birth-weight new born babies by anthropometric measurements in Bangladesh. AB - Birthweight is an important indicator of child survival. Appropriate and timely care of a newborn specially if he is born with low birthweight is important but this is difficult in developing countries since most of the deliveries are conducted at home where adequate facilities to weigh a new born does not exist. This study was conducted to find out a surrogate which could efficiently be used for detecting low birthweight babies at birth when no weighing machine is around. In this study 41% of the newborn babies were found to weigh less than 2,500 gm at birth. Out of this about 52% were females. The mean chest, thigh and mid-arm circumference at birth for males were 30.89 cm, 15.06 cm and 9.27 cm respectively with standard deviations of 1.83 cm, 1.30 cm and 1.04 cm. Corresponding figures for female babies were 30.69 cm, 15.14 cm and 9.25 cm respectively with standard deviations of 2.08 cm, 1.70 cm and 1.16 cm. Correlation co-efficient between normal birthweight and the chest, thigh and mid-arm circumference were 0.867, 0.845 and 0.842 respectively. A liner regression analysis showed that a chest circumference of 30.14 cm, a thigh circumference of 14.56 cm and a mid-arm circumference of 8.90 cm corresponded well with a birthweight of 2,500 gm. On this basis sensitivity, specificity and predictive values of the chest circumference was better than the other two measurements. However, the mid-arm circumference was observed to be more reliable than the other two measurements for detecting birthweight less than 2,000 gm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1879905 TI - Survey of village informants--an alternate method to estimate paralytic poliomyelitis prevalence in rural area. AB - Lameness surveys were conducted among children of 0-14 year age group in 60 villages of a Community Development Block of district Ambala in Haryana State. The methods used were: village informants survey and house-to-house survey. Village informants were village chief, school teachers, primary health care workers, traditional birth attendants and several prominent persons from each street/neighbourhood of the village. These informants located lame children in their locality. Subsequently, a house-to-house search for identification of lame children was made in all the 60 sampled villages. Physicians later on, examined the lame children to diagnose paralytic poliomyelitis. Estimate of the prevalence rate of lower extremity paralytic poliomyelitis in 0-14 year age group was found to be 7.9/1000 in village informants survey. This did not differ significantly from the rate of 8.8/1000 revealed by house-to-house survey in the same community (p greater than 0.05). Time required to complete village informants survey was almost one third and costs were also about half as compared to house-to-house survey. Therefore, village informants based lameness survey is a rapid and economical alternative for the estimation of poliomyelitis prevalence in rural communities. PMID- 1879906 TI - Congenital malformations--a retrospective study of 10,000 cases. AB - The frequency of congenital malformations in a retrospective study done on 10,000 consecutive births from January 1983 to March 1989 was 3.6%. The predominant system involved was CNS. Major malformations constituted 79.7% of the total. Malformations were seen 4 times more often among still births. The common malformations in still births were also of CNS. The frequency of malformations was similar in both the sexes, though genitourinary anomalies were commoner among male, while anencephaly in female babies. A statistically significant increase in the frequency of congenital malformations was observed with decreasing gestation and birth weight. There was a significant correlation between maternal factors, like previous abortions, drug intake and fever during 1st trimester, diabetes mellitus, pre-eclamptic toxemia, antepartum hemorrhage and congenital malformations in the baby. PMID- 1879907 TI - Anthropometry for syndromology. AB - In diagnosing certain syndromes, abnormal facial features such as hypertelorism, low set ears or wide nasolabial distance are taken into consideration. Most often the description is from a visual impression, which may prove wrong as it is only relative. Detailed studies have, so far been only from the west, except for two, from northern India. These values may not suit us as facial features and measurements vary in different populations. This study was undertaken to set up a standard for the south Indian population, to detect deviations and to compare our figures with those from other studies. Measurements were taken in 850 children, from birth to 11 years of age (horizontal study). The parameters studied were the inner and outer canthal distances, from which interpupillary distance was calculated; nasolabial distance, ear length, ear set, hand length and AF/AT ratio. The average measurements for various features (50th percentile) 3rd and 97th centile are presented in tables. Besides providing standards, this paper will aquaint the pediatricians on the need to actually measure the features rather than rely on ones impression on physical features in diagnosing syndromes. PMID- 1879908 TI - Facial anthropometry in newborns in Pondicherry. AB - Two hundred term healthy neonates were examined and 14 anthropometric measurements were taken in the face and ear region. Difference between the sexes was observed in ear length, ear breadth, and philtrum. Significant correlation was found between ear placement and ear length; and outer and inner canthal distances (p less than 0.001). The paper provides baselines data for facial growth measurements and discusses the utility of these measurements in detecting dysmorphogenesis in neonates. PMID- 1879909 TI - Influence of maternal literacy on the nutritional status of preschool children. AB - The impact of maternal literacy status on the nutritional status of pre-school children in Parbhani was studied. Results revealed that the children of literate mothers had better anthropometric measurements than children of illiterate mothers. Nutrient deficiency signs especially of protein energy malnutrition were more predominant among the children of illiterate mothers. Food consumption pattern was better in children with literate mothers as compared to children of illiterate mothers. The consumption of milk and milk products, fruits, sugar and jaggery was significantly greater in children with literate mothers. PMID- 1879911 TI - Fever phobia and the adaptive value of fever. PMID- 1879910 TI - Relation of childhood malnutrition to parental education and mothers' nutrition related KAP. AB - Severely malnourished children (26), weight for age 55.27 +/- 3.17, were identified in a colony of predominantly Muslim urban slum dwellers of low economic status. An equal number of normally nourished children matched for age, sex and per capita income were identified. A strong relation was found between nutritional status of the subjects and educational level of their mothers (P less than 0.025). Father's education was unrelated to childrens' nutritional status. A thirty seven point questionnaire was administered to the mothers to record their nutritional knowledge, attitudes and practices (KAP). Analysis revealed that better KAP in relation to 16 of these 37 questions was not associated with better nutritional status. Seven questions were found to have only a weak association. The remaining 14 questions were identified as important for a nutrition education programme. Comparison of nutritional KAP score based on these 14 questions in case of mothers of normal and severely malnourished children revealed a significantly higher score in the former. Questions related to growth monitoring and breast feeding were not found to be important. No significant association was found between mothers' KAP and educational level. It is concluded that (i) Maternal education and KAP are significantly and independently associated with childrens' nutritional status. (ii) The content areas of knowledge, attitudes and practices significantly associated with nutritional status pertain to nutritional requirements of children, nutritional value of foods, immunisation, hygiene, oral rehydration and diarrhea. PMID- 1879912 TI - Fetal diagnosis of the Meckel syndrome. PMID- 1879913 TI - A family with translocation 1/13: index patient with history of spontaneous abortions. PMID- 1879914 TI - Mouse liver contains a Pseudomonas aeruginosa exotoxin A-binding protein. AB - The opportunistic pathogen Pseudomonas aeruginosa produces several potential virulence factors, including the ADP-ribosylating toxin, exotoxin A (PE). Studies using a burned mouse model have shown that PE consistently inhibits protein synthesis and depletes elongation factor 2 in mouse liver and variably in other organs. One reason for toxin sensitivity could be the presence of a PE receptor on the surface of cells. Therefore we examined detergent extracts of mouse tissues for the presence of toxin-binding proteins. Proteins which specifically bind PE were present in extracts from liver, kidney, lung, spleen, and heart. Because liver appears to be a prominent target for the toxin in a burned animal, we choose to isolate the PE-binding protein from mouse liver and compare this protein to the recently characterized toxin-binding protein from toxin-sensitive mouse LM fibroblasts. The toxin-binding proteins from both sources have a molecular mass of approximately 350 kDa, share similar protease digestion profiles, and are glycosylated. However the glycosylation patterns for the two species are quite different. Both glycoproteins bind toxin with high avidity. The toxin-binding moiety is located, at least in part, on the plasma membrane and thus could represent the receptor involved in internalization of toxin molecules responsible for cell death. PMID- 1879915 TI - Actinobacillus pleuropneumoniae-induced thymic lesions in mice and pigs. AB - Actinobacillus pleuropneumoniae produces several hemolysins/cytotoxins that may be important in the pathogenesis of acute lesions. Little is known, however, about the role of these virulence factors in chronic disease or the carrier state. We investigated the effects of live bacterial infection and transthoracic injection of a sterile culture supernatant on primary lymphoid organs and lymphocyte populations. Transthoracic inoculation of mice or intranasal inoculation of pigs with virulent A. pleuropneumoniae serotypes 1 and 7 induced thymic cortical lymphoid necrosis. These lesions were reproduced in mice by transthoracic injection of a concentrated sterile culture supernatant. The cytotoxic effect of this culture supernatant was also demonstrated in vitro by using a tetrazolium dye reduction assay. Both porcine and murine thymic lymphocytes as well as splenic T lymphocytes were susceptible to the toxin. Porcine convalescent serum, but not preimmune serum, prevented thymic lesions and neutralized the in vitro cytotoxic effect of the culture supernatant on murine thymic lymphocytes. Thymic lesions also were reproduced in mice by using purified lipopolysaccharide (LPS) from Escherichia coli O111:B4; however, LPS had no in vitro cytotoxic effect on either porcine or murine thymic lymphocytes. These results suggest that secreted A. pleuropneumoniae toxin(s) is capable of affecting host T-lymphocyte populations and may affect host immune function. PMID- 1879916 TI - Distribution of the invA, -B, -C, and -D genes of Salmonella typhimurium among other Salmonella serovars: invA mutants of Salmonella typhi are deficient for entry into mammalian cells. AB - Invasion of intestinal epithelial cells is an essential virulence factor of salmonellae. A group of genes, invABC and invD, that allow Salmonella typhimurium to penetrate cultured epithelial cells have previously been characterized (J. E. Galan and R. Curtiss III, Proc. Natl. Acad. Sci. USA 86:6383-6387, 1989). The distribution of these genes among Salmonella isolates belonging to 37 different species or serovars was investigated by Southern and colony blot hybridization analyses. Regions of high sequence similarity to the invABC genes were present in all Salonella isolates examined, while regions of sequence similarity to the invD gene were present in all but one (S. arizonae) of the isolates tested, with little restriction fragment length polymorphism. Sequences similar to these genes were not detected in strains of Escherichia coli, Yersinia spp., or Shigella spp. invA mutants (unable to express the invABC genes) of several Salmonella species or serovars, including S. typhi, were constructed and examined for their ability to penetrate Henle-407 cells. All mutants were deficient for entry into cultured epithelial cells, indicating that the invABC genes were not only present in these strains but also functional. PMID- 1879917 TI - Persistence of Escherichia coli bacteriuria is not determined by bacterial adherence. AB - The role of bacterial adherence in the persistence of bacteria in the human urinary tract was analyzed. Women with chronic symptomatic urinary tract infections were subjected to deliberate colonization with nonvirulent Escherichia coli, after eradication of their current infections. E. coli organisms were instilled into the bladder through a catheter. The strain used for colonization, E. coli 83972, was isolated from a patient with stable bacteriuria. It lacked expressed adherence factors and did not belong to the uropathogenic O:K:H serotypes. Strain 83972 was transformed with the pap and pil DNA sequences encoding Gal alpha 1-4Gal beta- and mannose-specific (type 1) adhesins. Patients were colonized with a mixture of the wild-type and the transformed strains. E. coli 83972 caused stable bacteriuria for greater than 30 days in 7 of 12 individuals. In contrast, the Gal alpha 1-4 Gal beta-recognizing or mannose binding transformants were eliminated within 48 h. The consistent superiority of the wild-type strain in establishing stable bacteriuria when compared with the adhesive transformants did not appear to be due to differences in growth rates or to plasmid segregation. Rather, the transformants expressing the adhesin determinants were selectively eliminated by the host. This suggested that the acquisition of adherence factors is not sufficient to increase the fitness of E. coli for survival in the urinary tract of humans. PMID- 1879918 TI - Live vaccine strain of Francisella tularensis: infection and immunity in mice. AB - The live vaccine strain (LVS) of Francisella tularensis caused lethal disease in several mouse strains. Lethality depended upon the dose and route of inoculation. The lethal dose for 50% of the mice (LD50) in four of six mouse strains (A/J, BALB/cHSD, C3H/HeNHSD, and SWR/J) given an intraperitoneal (i.p.) inoculation was less than 10 CFU. For the other two strains tested, C3H/HeJ and C57BL/6J, the i.p. log LD50 was 1.5 and 2.7, respectively. Similar susceptibility was observed in mice inoculated by intravenous (i.v.) and intranasal (i.n.) routes: in all cases the LD50 was less than 1,000 CFU. Regardless of the inoculation route (i.p., i.v., or i.n.), bacteria were isolated from spleen, liver, and lungs within 3 days of introduction of bacteria; numbers of bacteria increased in these infected organs over 5 days. In contrast to the other routes of inoculation, mice injected with LVS intradermally (i.d.) survived infection: the LD50 of LVS by this route was much greater than 10(5) CFU. This difference in susceptibility was not due solely to local effects at the dermal site of inoculation, since bacteria were isolated from the spleen, liver, and lungs within 3 days by this route as well. The i.d.-infected mice were immune to an otherwise lethal i.p. challenge with as many as 10(4) CFU, and immunity could be transferred with either serum, whole spleen cells, or nonadherent spleen cells (but not Ig+ cells). A variety of infectious agents induce different disease syndromes depending on the route of entry. Francisella LVS infection in mice provides a model system for analysis of locally induced protective effector mechanisms. PMID- 1879919 TI - Toxic shock syndrome toxin 1 enhances synthesis of endotoxin-induced tumor necrosis factor in mice. AB - Toxic shock syndrome toxin 1 (TSST-1) was tested for its ability to enhance the production of endotoxin-induced tumor necrosis factor (TNF) in C3H/HeN mice. The TNF level in serum was quantified by a sandwich enzyme-linked immunosorbent assay (ELISA). It was found that when mice were injected with 20 micrograms of TSST-1 12 h before exposure to 1 micrograms of endotoxin, the serum endotoxin-induced TNF was 20 times as high as that found in mice exposed to endotoxin alone. Although 20 micrograms of TSST-1 did induce a maximum level of near 1 ng of TNF per ml of serum 1.5 h after exposure, the TNF concentration was greatly diminished after 5 to 6 h and was no longer detectable after 12 h. Pretreatment of mice with 20 micrograms of TSST-1 or 1 micrograms of endotoxin did not influence TNF induction by TSST-1 12 h later. Also, pretreatment of mice with 1 micrograms of endotoxin did not enhance TNF induction by endotoxin 12 h later. Enhancement was achieved only when mice were exposed to TSST-1 more than 4 h and less than 24 h before injection of endotoxin. Despite the relatively high serum TNF levels (30 to 50 ng/ml), no mortality was observed in the mice treated with both TSST and endotoxin. PMID- 1879920 TI - Delineation of a segment of adsorbed salivary acidic proline-rich proteins which promotes adhesion of Streptococcus gordonii to apatitic surfaces. AB - Cells of several strains of Streptococcus gordonii attached in much higher numbers to experimental pellicles formed from samples of submandibular or parotid saliva on hydroxyapatite (HA) beads than to buffer controls. The nature of the salivary components responsible were investigated by preparing experimental pellicles from chromatographic fractions of submandibular saliva obtained from Trisacryl GF 2000M columns. Adhesion of S. gordonii Blackburn was promoted by two groups of fractions. The adhesion-promoting activity in the first group of fractions was associated with the family of acidic proline-rich proteins (PRPs), while that of the second group is as yet unidentified. Experimental pellicles prepared by treating HA with 2 micrograms of pure 150-amino-acid-residue PRPs (PRP-1, PRP-2, and PIF-s) promoted adhesion of S. gordonii Blackburn cells to an extent comparable to that obtained with unfractionated saliva. However, pellicles prepared from a 106-residue PRP (PRP-3) were significantly less effective, and those prepared from the amino-terminal tryptic peptide (residues 1 to 30) of the PRP and the salivary phosphoprotein statherin were completely ineffective in promoting adhesion. Although adhesion of several strains of S. gordonii was promoted by adsorbed PRP-1, the adhesion of several strains of Streptococcus sanguis or Streptococcus oralis was either not affected or only weakly enhanced by this protein. S. gordonii cells bound avidly to PRPs adsorbed onto HA beads, but the streptococci did not appear to bind PRPs in solution, since concentrations of PRP as high as 200 micrograms/ml did not inhibit binding of bacterial cells to pellicles prepared from pure PRP. S. gordonii cells also attached well to PRP or a synthetic decapeptide representing residues 142 to 150 of the PRP when the peptide was linked to agarose beads. Studies with a series of synthetic decapeptides indicated that the minimal segment of PRP which promoted high levels of S. gordonii adhesion was the carboxy-terminal dipeptide Pro-Gln (residues 149 and 150). PMID- 1879921 TI - Molecular cloning of the secretory acid proteinase gene from Candida albicans and its use as a species-specific probe. AB - Candida albicans secretes an acid proteinase when grown with a protein as a sole nitrogen source. The gene encoding this proteinase was isolated from a genomic expression library of C. albicans constructed in lambda gt11 by screening with antiproteinase antibodies. The affinity-purified antibodies used to verify the clones are monspecific; these do not cross-react with any other protein in the culture supernatants or crude extracts of C. albicans but strongly react with fusion proteins encoded by recombinant clones, revealing that these are true proteinase clones. Genomic Southern blot analysis shows that the proteinase gene is present at a unique locus and that there is no other closely related gene in the C. albicans genome. The proteinase gene probe identified two transcripts on Northern blots (RNA blots), which are present at a much higher level in C. albicans cells induced for proteinase secretion than in uninduced cells. The aspartyl proteinase gene reported earlier (T.J. Lott, L.S. Page, P. Boiron, J. Benson, and E. Reiss, Nucleic Acids Res. 17:1779, 1989) is not that of secretory acid proteinase, since the N-terminal amino acid sequence of secretory acid proteinase does not correspond to the deduced amino acid sequence of the aspartyl proteinase gene. The secretory acid proteinase gene was used to probe Southern blots of genomic DNA of several medically important Candida species and Saccharomyces cerevisiae. Under hybridization and wash conditions of low stringency, Candida tropicalis and Candida parapsilosis, in addition to C. albicans strains, gave specific signals, implying that C. tropicalis and C. parapsilosis have homologous secretory acid proteinase genes. However, under under wash conditions of high stringency, signals were obtained only with C. albicans strains, suggesting that this gene can be used as a species-specific probe. A simple yeast colony hybridization technique is sufficient to distinguish C. albicans from other yeasts. PMID- 1879922 TI - Biodegradable and biocompatible poly(DL-lactide-co-glycolide) microspheres as an adjuvant for staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies. AB - Microspheres composed of biocompatible, biodegradable poly(DL-lactide-co glycolide) (DL-PLG) and staphylococcal enterotoxin B (SEB) toxoid were evaluated as a vaccine delivery system when subcutaneously injected into mice. As measured by circulating immunoglobulin G (IgG) antitoxin titers, the delivery of SEB toxoid via DL-PLG microspheres, 1 to 10 microns in diameter, induced an immune response which was approximately 500 times that seen with nonencapsulated toxoid. The kinetics, magnitude, and duration of the antitoxin response induced with microencapsulated toxoid were similar to those obtained when an equal toxoid dose was administered as an emulsion with complete Freund adjuvant. However, the microspheres did not induce the inflammation and granulomata formation seen with complete Freund adjuvant. The adjuvant activity of the microspheres was not dependent on the superantigenicity of SEB toxin and was equally effective at potentiating circulating IgG antitrinitrophenyl levels in response to microencapsulated trinitrophenyl-keyhole limpet hemocyanin. Empty DL-PLG microspheres were not mitogenic, and SEB toxoid injected as a mixture with empty DL-PLG microspheres was no more effective as an immunogen than toxoid alone. Antigen-containing microspheres 1 to 10 microns in diameter exhibited stronger adjuvant activity than those greater than 10 microns, which correlated with the delivery of the 1- to 10-microns, but not the greater than 10-microns, microspheres into the draining lymph nodes within macrophages. The antibody response induced through immunization with microencapsulated SEB toxoid was protective against the weight loss and splenic V beta 8+ T-cell expansion induced by intravenous toxin administration. These results show that DL-PLG microsphere vaccine delivery systems, which are composed of pharmaceutically acceptable components, possess a strong adjuvant activity for their encapsulated antigens. PMID- 1879923 TI - Human immune response to an iron-repressible outer membrane protein of Bacteroides fragilis. AB - Under conditions of iron starvation, Bacteroides fragilis expresses various iron repressible outer membrane proteins (IROMPs). A 44-kDa protein appears to be one of the major outer membrane proteins (OMPs) in B. fragilis under iron stress and plays a role in heme uptake by this bacterium. To determine whether the 44-kDa IROMP of B. fragilis is expressed in vivo and whether this protein is immunogenic, we used Western immunoblotting to examine serum samples from patients with an infection caused by Bacteroides species. All the serum samples from patients and from normal controls showed reactivity with several proteins of B. fragilis. Only serum samples from patients infected with B. fragilis showed immunoreactivity with the 44-kDa protein. We also used a rat infection model to study the immune response against this protein during the process of an intra abdominal infection in these animals. During the first 8 days of infection a gradual increase of antibodies to the 44-kDa protein in the rat was detected. These results suggest that the 44-kDa IROMP is expressed in vivo, since it induces an antibody response in patients and animals. We also analyzed 85 strains of the B. fragilis group for the presence of proteins antigenically related to the B. fragilis 44-kDa protein. The data indicate that this protein was conserved in B. fragilis strains and was absent in the other bacterial strains tested. PMID- 1879924 TI - Protective effect of Porphyromonas gingivalis outer membrane vesicles against bactericidal activity of human serum. AB - The present study was undertaken to evaluate the effect of Porphyromonas gingivalis outer membrane vesicles on the bactericidal activity of human serum. Human serum was pretreated with extracellular vesicles and then incubated with a cell suspension of Capnocytophaga ochracea. After 2 h at 37 degrees C, the percent viability of C. ochracea was determined by cultivation on blood agar plates. At a final concentration of 0.3 mg/ml, outer membrane vesicles completely inhibited the serum bactericidal activity against C. ochracea. Boiling the vesicles prevented this inhibition. However, partial inhibition of the serum lethal action was obtained when a higher concentration (1.5 mg/ml) of boiled vesicles was used, which indicates the involvement of both heat-labile and heat stable components associated with vesicles. Combining vesicles at a suboptimal concentration (0.1 mg/ml) with a reducing agent brought back inhibition of the bactericidal activity, whereas combining vesicles at an optimal concentration (0.3 mg/ml) with a thiol-blocking reagent caused a restoration of the bactericidal activity. When a purified preparation of P. gingivalis lipopolysaccharides was used instead of vesicles, inhibition of the bactericidal activity was also observed. These results indicate that the lipopolysaccharides and the proteolytic enzyme(s) associated with P. gingivalis outer membrane vesicles are likely to represent the heat-stable and the heat-labile components, respectively. It is possible that outer membrane vesicles released by P. gingivalis protect other bacterial species from complement action, thus favoring the pathogenic process of periodontal disease. PMID- 1879925 TI - Live but not heat-killed mycobacteria cause rapid chemotaxis of large numbers of eosinophils in vivo and are ingested by the attracted granulocytes. AB - We studied leukocyte chemotaxis triggered by a local injection of mycobacteria (Mycobacterium avium and M. smegmatis) in BALB/c and C57BL/6 mice. Our experimental model consisted of the induction of a subcutaneous air pouch in the dorsal area of mice and inoculation 6 days later of 10(8) CFU of myocobacteria. Inflammatory exudates were harvested from the air pouch cavities 15, 30, and 45 min after the injection of the inocula. Injection of the microorganisms resulted in the migration of an elevated number of eosinophilic granulocytes into the inflammatory cavities. At 30 min after the inoculation of the mycobacteria, the air pouches contained between (3.9 +/- 0.3) x 10(5) (M. avium) and (3.3 +/- 0.3) x 10(5) (M. smegmatis) eosinophils, corresponding to more than one-third (41.4 to 38.3%) of the leukocytes present in the inflammatory cavities. Less than one-half of the eosinophils were attracted to the air pouches when the same number of heat killed mycobacteria were inoculated [(1.3 +/- 0.2) x 10(5) cells for M. avium and (1.5 +/- 0.2) x 10(5) cells for M. smegmatis]. Injection of gram-negative bacteria (Escherichia coli), of latex beads, or of casein resulted in the attraction of inflammatory eosinophils in numbers that were comparable to those attracted by the heat-killed mycobacteria. Our data document the fact that live mycobacteria exert a rapid chemotactic effect on eosinophils. We therefore postulate that mycobacteria either contain or induce the production of an eosinophilotactic factor. Because this chemotactic effect occurs during the acute inflammatory response to mycobacteria, it cannot be due to the formation of immune complexes (a major infection-associated chemotactic factor for eosinophils). The attracted eosinophils had an important role in the local phagocytosis of mycobacteria, as indicated by our finding, derived from thin section electron microscopy quantifications, that at 30 min after M. avium inoculation the inflammatory exudates contained (2.2 +/- 0.5) x 10(5) mycobacterium-bearing eosinophils (corresponding to 57% of the total eosinophils), as compared with (2.1 +/- 0.1) x 10(5) neutrophils and (1.5 +/- 0.2) x 10(5) macrophages with ingested bacilli. We conclude that mycobacteria induce the attraction of eosinophils to inflammatory sites and that these granulocytes have the capacity to phagocytize these bacilli in situ. PMID- 1879926 TI - In vitro killing of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. by human neutrophil cathepsin G and elastase. AB - The purpose of this study was to compare the killing of Actinobacillus actinomycetemcomitans with that of Capnocytophaga spp. by purified cathepsin G and elastase in vitro. Both were sensitive to killing by purified cathepsin G, but only the Capnocytophaga spp. were killed by elastase. Killing by cathepsin G exhibited logarithmic kinetics, was enhanced slightly by alkaline pH, and was enhanced greatly under hypotonic conditions. Treatment of cathepsin G with diisopropyl fluorophosphate significantly reduced its bactericidal activity against Capnocytophaga spp. but not against Escherichia coli or A. actinomycetemcomitans. The bactericidal effects of cathepsin G against Capnocytophaga sputigena and A. actinomycetemcomitans were inhibited by alpha-1 antichymotrypsin, alpha-1-antitrypsin, and alpha-2-macroglobulin but not by bovine serum albumin. We conclude that (i) cathepsin G kills Capnocytophaga spp. and A. actinomycetemcomitans, (ii) elastase kills Capnocytophaga spp., (iii) the bactericidal activity of cathepsin G is enzyme dependent against Capnocytophaga spp. and enzyme independent against A. actinomycetemcomitans, and (iv) natural plasma antiproteases may control both enzyme-dependent and enzyme-independent bactericidal activities of cathepsin G. PMID- 1879927 TI - Increase in tumor necrosis factor alpha- and interleukin-6-secreting cells in peripheral blood mononuclear cells from subjects infected with Mycobacterium tuberculosis. AB - We detected and quantified tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) from monocytes/macrophages (M phi) in the peripheral blood of subjects from three different population groups, i.e., tuberculin-negative healthy subjects, tuberculin-positive healthy subjects, and patients with active pulmonary tuberculosis. TNF-alpha or IL-6 activity in the culture supernatant of these cells was determined by the cytotoxicity of murine L-929 cells or by enzyme linked immunosorbent assay, respectively. Detection and enumeration of cells secreting either TNF-alpha or IL-6 were performed by an adaptation of the enzyme linked immunospot assay. Monocytes/M phi from tuberculin-positive healthy subjects or patients with tuberculosis showed higher TNF-alpha- and IL-6 producing activities than those from tuberculin-negative healthy subjects. The number of TNF-alpha- and IL-6-secreting cells in either lipopolysaccharide- or muramyl dipeptide-stimulated mononuclear cells from tuberculin-positive healthy subjects and patients was significantly higher than that in cells from the tuberculin-negative healthy subjects. PMID- 1879928 TI - Nucleotide sequence of the hemolysin I gene from Actinobacillus pleuropneumoniae. AB - The DNA sequence of the gene encoding the structural protein of hemolysin I (HlyI) of Actinobacillus pleuropneumoniae serotype 1 strain 4074 was analyzed. The nucleotide sequence shows a 3,072-bp reading frame encoding a protein of 1,023 amino acids with a calculated molecular size of 110.1 kDa. This corresponds to the HlyI protein, which has an apparent molecular size on sodium dodecyl sulfate gels of 105 kDa. The structure of the protein derived from the DNA sequence shows three hydrophobic regions in the N-terminal part of the protein, 13 glycine-rich domains in the second half of the protein, and a hydrophilic C terminal area, all of which are typical of the cytotoxins of the RTX (repeats in the structural toxin) toxin family. The derived amino acid sequence of HlyI shows 42% homology with the hemolysin of A. pleuropneumoniae serotype 5, 41% homology with the leukotoxin of Pasteurella haemolytica, and 56% homology with the Escherichia coli alpha-hemolysin. The 13 glycine-rich repeats and three hydrophobic areas of the HlyI sequence show more similarity to the E. coli alpha hemolysin than to either the A. pleuropneumoniae serotype 5 hemolysin or the leukotoxin (while the last two are more similar to each other). Two types of RTX hemolysins therefore seem to be present in A. pleuropneumoniae, one (HlyI) resembling the alpha-hemolysin and a second more closely related to the leukotoxin. Ca(2+)-binding experiments using HlyI and recombinant A. pleuropneumoniae prohemolysin (HlyIA) that was produced in E. coli shows that HlyI binds 45Ca2+, probably because of the 13 glycine-rich repeated domains. Activation of the prohemolysin is not required for Ca2+ binding. PMID- 1879929 TI - Endocytic mechanisms utilized by chlamydiae and their influence on induction of productive infection. AB - The microfilament-disrupting drug cytochalasin D and, initially, inoculation at 20 degrees C were used to differentiate between phagocytosis (sensitive to both treatments) and pinocytosis (resistant to both treatments) to assess whether chlamydial uptake into McCoy cells occurred by one or both mechanisms and whether each could contribute to productive infection. Both treatments suppressed the infectivity of Chlamydia trachomatis L2/434/Bu and C. psittaci GPIC (the guinea pig inclusion conjunctivitis strain) following static inoculation by only 50%, indicating that there was simultaneous operation of both phagocytosis and pinocytosis during uptake that led to productive infection. Measurement of the entry of organisms by two separate assays established that both strains predominantly used a cytochalasin D-resistant (pinocytic) mechanism, implying that phagocytic uptake was coupled to a higher frequency of productive infection. Integration of the data on infectivity and entry allowed the potential for an organism to infect a host cell to be quantified. This synthesis revealed that for both strains the infectivity potential following phagocytic entry was ca. 10-fold greater than that following pinocytic entry. However, both entry mechanisms were exploited more efficiently by strain L2/434/Bu than by strain GPIC (unless the latter was inoculated with centrifugation), indicating that intrinsic strain properties are more important for infectivity potential than the endocytic mechanism utilized. PMID- 1879930 TI - Purification and characterization of three types of proteases from culture supernatants of Porphyromonas gingivalis. AB - Three types of caseinolytic proteases (Pase-A, Pase-B, and Pase-C) were isolated and purified from culture supernatants of Porphyromonas gingivalis 381 by the combined procedures of acetone precipitation, gel filtration, solubilization with octylthioglucoside followed by affinity chromatography on arginine-Sepharose 4B, high-performance liquid chromatography (HPLC) on Biofine IEC-DEAE, and HPLC on TSK-G4000SW. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Pase-A and -B showed diffuse protein bands of 105 to 110 and 72 to 80 kDa, respectively, and Pase-C showed a clear band of about 44 kDa. Pase-B and -C hydrolyzed some synthetic substrates for trypsin, but Pase-B did not act on the carboxyl side of lysine in insulin chain B or on a synthetic substrate which trypsin and Pase-C acted on. Pase-A did not act on the synthetic substrates but cleaved the peptide bonds Glu-Ala and Ala-Leu of insulin. Leupeptin inhibition of the caseinolytic activity of both Pase-A and -B was similar to its inhibition of Pase-C. Phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate strongly inhibited Pase-A, but no significant effect on the other enzymes was observed, suggesting that only Pase-A is a serine protease. The inhibitory characteristics of Pase-B and -C were very similar. Pase-A was not thiol dependent for enzyme activity, but Pase-B was strongly dependent, i.e., even more so than Pase-C. Pase-A inactivated the inhibitory activity of plasma alpha-1-antitrypsin, but the other two did not. These results show that P. gingivalis produces different types of proteases other than the trypsinlike protease generally reported. PMID- 1879931 TI - Adherence of Candida albicans to tissues from mice with genetic immunodeficiencies. AB - Ex vivo adherence comparisons were made between immunocompetent and immunocompromised mouse tissues, and the roles of serum immunoglobulin and macrophages in the adherence of Candida albicans were investigated. Spleen, lymph node, and kidney tissues were harvested from congenitally immunodeficient mice, including AKR/scid, C.B-17, C3Hscid, and N:NIH nu/bg/xid mice, and their normal counterparts into which the defects were bred (AKR/J, C3H/HeSnJ, and BALB/c-ByJ). Tissues were compared for the ability to bind C. albicans 219 in an ex vivo assay. In general, immunodeficiencies significantly decreased binding of C. albicans to spleen but not to lymph node or kidney tissue compared with immunocompetent mice. In C3Hscid and AKRscid mice, spleen tissues from "nonleaky" mice bound significantly fewer yeast cells (P = 0.0005 and 0.0009, respectively) than did those from C3H/HeSnJ or AKR/J mice. Numbers of adherent yeast cells were similar in "leaky" AKRscid and AKR/J mice. Yeast adherence to spleen tissue from N:NIH nu/bg/xid mice correlated with mouse age (P = 0.01). Measurements of total serum immunoglobulin indicated that the scid defect was most complete in C3Hscid mice and that yeast adherence in spleen tissue correlated with immunoglobulin titers. Results of adherence assays and macrophage-specific immunostains suggested that factors determining adherence differ among reticuloendothelial organs. PMID- 1879932 TI - Identification of hemolytic and cytotoxic proteins of Actinobacillus pleuropneumoniae by use of monoclonal antibodies. AB - Monoclonal antibodies (MAbs) were raised against extracellular hemolytic and cytotoxic proteins of Actinobacillus pleuropneumoniae serotypes 2 and 9. MAbs were tested for inhibition of hemolytic and cytotoxic activities of the reference strains of A. pleuropneumoniae serotypes 1 to 12. Five MAbs inhibited hemolytic or cytotoxic activities of one or more serotypes and were used to probe Western blots (immunoblots) of cytotoxic and hemolytic culture filtrates of serotypes 1 to 12. The MAbs recognized three different proteins: (i) a protein of approximately 103 kDa that was associated with a weak hemolytic activity and a moderate cytotoxic activity, (ii) a protein of approximately 105 kDa that was associated with a strong hemolytic activity and a strong cytotoxic activity, and (iii) a protein of approximately 120 kDa that was associated with a strong cytotoxic activity but not with hemolytic activity. Serotypes 6, 7, and 12 produced only the 103-kDa protein, and serotype 10 produced only the 105-kDa protein. The other serotypes produced two proteins: serotypes 1, 5, 9, and 11 produced the 103- and 105-kDa proteins, and serotypes 2, 3, 4, and 8 produced the 103- and 120-kDa proteins. PMID- 1879933 TI - Differential effect of aging on B-cell immune responses to cholera toxin in the inductive and effector sites of the mucosal immune system. AB - The age-associated primary immune response of B cells from the Peyer's patches (PP), the lamina propria (LP), the mesenteric lymph nodes (MLN), and the spleen of mice following oral immunization with cholera toxin (CTx) was investigated. The induction of immune responses was assessed in 4-, 11-, and 24-month-old, individual C57BL/6J male mice by determining the number and isotype of anti-CTx ELISPOT-forming cells (SFC) in the PP, LPL, MLN, and spleen and the titer and isotype of serum anti-CTx antibody. The data indicate a significant age associated decline in immunoglobulin G (IgG) and IgA anti-CTx SFC in the LP B cells but only in IgA anti-CTx SFC in the PP. No decline was seen in the anti-CTx SFC response in the MLN and spleen. Peroral immunization of mice with CTx resulted in a serum anti-CTx antibody response which was predominantly of the IgG class in all three age groups of mice tested. There was no age-associated decline in anti-CTx IgM, IgG, or IgA titers in serum. Isoelectric focusing and affinity immunoblotting revealed several distinct new antibody clonotypes in the immune serum of old mice following oral immunization with CTx. The results indicate a loss of immune responsiveness to CTx following oral immunization in senescent PP and LP B cells. The MLN and spleen B-cell responses were found to be refractory to the loss of immune function with aging. These findings suggest a differential effect of aging in the inductive and effector sites of the mucosal immune system, and the loss of antigen-specific IgA responses at mucosal sites may have adverse effects on the host's defense against potential pathogens. PMID- 1879934 TI - Susceptibility of inbred mouse strains to infection with Serpula (Treponema) hyodysenteriae. AB - Several inbred strains of mice were inoculated with Serpula (Treponema) hyodysenteriae B204 to determine susceptibility to infection. Challenge doses of 10(7) or 10(8) spirochetes induced cecal lesions in C3H/HeJ mice and other C3H strains of mice. However, more than a 100-fold difference existed between the dose required to induce lesions in 50% of the infected C3H/HeJ mice (8.3 x 10(7)) and that required to induce them in 50% of the infected C3H/HeN mice (5 x 10(5)). C3H/HeJ mice lack a splenocyte mitogenic response to Escherichia coli lipopolysaccharide but exhibited a mitogenic response comparable to those of other C3H strains of mice when stimulated with S. hyodysenteriae endotoxin (butanol-water extract). Different inbred strains exhibited different susceptibilities to infection, with the strain C3H/HeN being the most susceptible on the basis of colonization and development of macroscopic cecal lesions. The ity gene had no apparent effect on susceptibility of mice challenged with S. hyodysenteriae. The involvement of the H-2 haplotype with susceptibility is unclear, but the mice bearing H-2k were more susceptible than mice with the H-2b, H-2d, or H-2q haplotype. These data support the hypothesis that the host's responsiveness to lipopolysaccharide influences the susceptibility to infection with S. hyodysenteriae. However, differences in susceptibility between inbred mice exist independent of the lps locus, suggesting that there are other inherent differences between mouse strains that affect susceptibility to infection by S. hyodysenteriae. PMID- 1879935 TI - Activation of bovine neutrophils by partially purified Pasteurella haemolytica leukotoxin. AB - In this study we developed a new method for the partial purification of Pasteurella haemolytica leukotoxin by size-exclusion high-performance liquid chromatography. The partially purified leukotoxin had a molecular weight of 104,000, as estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and reacted on an immunoblot with an antileukotoxin monoclonal antibody. As expected, high concentrations of the leukotoxin were inhibitory or lethal to bovine neutrophils. Incubation of bovine neutrophils with diluted leukotoxin, however, resulted in significant neutrophil activation that was comparable in magnitude to that obtained with standard activating agents such as opsonized zymosan or zymosan-activated serum. Dilute leukotoxin (1:128 to 1:8,192 dilutions) stimulated an oxidative burst (luminol-dependent chemiluminescence) by bovine neutrophils that was comparable in magnitude to that obtained with opsonized zymosan. Preincubation with leukotoxin did not significantly prime the neutrophils for an enhanced oxidative burst when they were then exposed to opsonized zymosan as a second stimulus. Dilute leukotoxin (1:100 to 1:1,000 dilutions) also stimulated cytoskeletal alterations in bovine neutrophils, as measured by a significant shape change response. Preferential release of secondary granule constituents (lactoferrin) occurred when neutrophils were incubated with 1:100 to 1:500 dilutions of leukotoxin. Significant release of primary granules, as measured by beta-glucosaminidase activity, was not observed except at low dilutions (1:20) of leukotoxin that resulted in significant release of cytosolic constituents (i.e., lactate dehydrogenase activity). The neutrophil activating activity of the leukotoxin was heat labile, unaffected by polymyxin B, and abrogated by a leukotoxin-neutralizing monoclonal antibody. These data indicate that P. haemolytica leukotoxin, like the closely related Escherichia coli hemolysin, is a potent neutrophil-activating agent. Leukotoxin-stimulated release of neutrophil oxygen intermediates and granule constituents may contribute to the intense inflammation that characterizes bovine pulmonary pasteurellosis. PMID- 1879936 TI - Cells within the vascular system capable of mediating trypanocidal activity in vitro. AB - Cure of Trypanosoma musculi infection involves an effector mechanism mediated by immunoglobulin G2a antibody, C3, and an unidentified effector cell. In the present study, experiments were designed to identify the cell(s) within the vascular system that may be responsible for cure of trypanosomiasis. The ability of various cell populations to mediate killing of trypanosomes in the presence of C3 and immune plasma (IP) was tested in vitro. Blood-derived platelets or leukocytes or Bio-Gel-elicited macrophages or neutrophils were incubated at various concentrations with T. musculi, C3, and IP diluted up to 1 in 8. Trypanocidal activity was dependent upon the presence and concentration of IP and on the number of cells in the wells. Macrophages, neutrophils, and platelets were shown to kill with different potencies. With a 2:1 cell-to-parasite ratio, both macrophages and neutrophils reduced parasite numbers by 2 log, while platelets at a 40:1 ratio mediated a 1 log decrease. In addition, even in the absence of C3, the phagocytes were capable of killing trypanosomes while platelet trypanocidal activity was abrogated. The time course of trypanocidal activity was monitored for macrophages and neutrophils. The number of parasites decreased by 0.5 log by 4 h and 1 to 2 log by 8 h and by 20 h was reduced to zero. Cultured monolayers of endothelial cells were also tested for trypanocidal activity and shown to kill the parasites in the presence of IP and C3. The level of trypanocidal activity was dependent on the concentration of IP. PMID- 1879937 TI - Identification of two proteins associated with virulence of Streptococcus suis type 2. AB - The protein profiles of various cell fractions of 180 strains of Streptococcus suis type 2, which were isolated from diseased pigs, from healthy pigs when they were slaughtered, and from human patients, were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The isolates from diseased pigs contained two proteins that were absent in most of the isolates from healthy pigs. One of these proteins was a 136-kDa protein that was previously identified as the muramidase-released protein (MRP). This protein was predominantly detected in protoplast supernatants and culture supernatants. The second protein was a 110-kDa protein that was detected only in culture supernatants and therefore was provisionally called extracellular factor (EF). Three phenotypes of S. suis type 2 strains were recognized. Isolates from organs of diseased pigs mainly belonged to the MRP+ EF+ phenotype (77%), while isolates from tonsils of healthy pigs mainly had the MRP- EF- phenotype (86%). Most of the isolates from human patients contained MRP (89%); 74% had the MRP+ EF- phenotype. These findings confirm the results of previous investigations which demonstrated that S. suis type 2 strains differ in virulence. Monoclonal antibodies raised against the 110-kDa EF recognized proteins with higher molecular weights in culture supernatants of all of the strains with the MRP+ EF- phenotype. However, none of the strains with the MRP+ EF+ phenotype produced these high-molecular weight proteins. Our results demonstrate that MRP and EF are associated with virulence. This suggests that one or both of these proteins are virulence factors that play a role in the pathogenesis of S. suis type 2 infections in pigs and human patients. PMID- 1879938 TI - The T-cell-stimulating 17-kilodalton protein of Francisella tularensis LVS is a lipoprotein. AB - A T-cell-stimulating, membrane-located 17-kDa protein of the live vaccine strain Francisella tularensis LVS has previously been cloned and sequenced. In the present study, it is shown to be a lipoprotein. When F. tularensis was grown in the presence of [3H]palmitate, several proteins of the organism, including a 17 kDa protein, were radiolabeled. The labeled 17-kDa protein was found by Western blot (immunoblot) analysis to be identical to the cloned protein. It was located in the detergent phase after partitioning with the nonionic detergent Triton X 114, thereby behaving like a hydrophobic integral membrane protein. The protein was predominantly hydrophilic and contained no putative transmembrane domain. The presence of fatty acids is therefore the probable explanation of the membrane location of the 17-kDa protein. The amino acid sequence of the 17-kDa protein contains the tetrapeptide Leu-Ala-Ser-Cys, which is a recognition sequence of the lipoprotein signal peptidase. Globomycin, a specific inhibitor of the peptidase, inhibited maturation of the 17-kDa lipoprotein. The protein incorporated [3H]palmitate also when expressed by Escherichia coli. The 17-kDa lipoprotein was recognized not only by T cells but also by serum antibodies of F. tularensis primed individuals. PMID- 1879939 TI - Isolation of an intracellular bacterium from hamsters (Mesocricetus auratus) with proliferative ileitis and reproduction of the disease with a pure culture. AB - An intracellular bacterium was isolated from hamsters (Mesocricetus auratus) with proliferative ileitis. The organism was isolated in Intestine 407 and GPC-16 cell cultures (incubated in a microaerophilic atmosphere) from isolated and lysed epithelial cells from hamsters with proliferative ileitis. The bacterium measured 1.4 to 1.7 microns in length by 0.26 to 0.34 microns in width, was slightly curved, and had an irregular trilaminar cell wall. Inoculation of hamsters with a cell culture lysate containing the organism or a 0.65-microns-pore-size filtrate of an infected-cell lysate resulted in the typical lesions of proliferative ileitis in approximately 50% of the animals in 28 days. Hamsters inoculated with uninfected cells or a 0.2-microns-pore-size filtrate of an infected-cell lysate remained uninfected. Attempts to propagate the organism on cell-free media have been unsuccessful. PMID- 1879940 TI - Lethal effects of Actinobacillus actinomycetemcomitans leukotoxin on human T lymphocytes. AB - The majority of strains of Actinobacillus actinomycetemcomitans isolated from patients with periodontal diseases secrete a leukotoxin that destroys human myeloid cells within minutes but has no effect on viability of peripheral blood lymphocytes in culture for 1.5 h. However, since this organism persists in the gingival crevice and thus may continuously release toxin over extended periods of time, we assessed the viability of T cells cultured with leukotoxin (0 to 250 ng/ml) for up to 2 days. Although the total numbers of cells recovered from cultures with or without leukotoxin were equivalent, leukotoxin killed up to 70% of the T cells in a time- and concentration-dependent manner. Cell death was associated with uptake of propidium iodide, release of 51Cr from the cytoplasm, and morphological evidence of damage to the plasma membrane and apoptosis. Leukotoxin also induced increased cleavage of chromosomal DNA into nucleosome sized fragments, suggesting activation of an endogenous nuclease in the T cells. These data suggest that leukotoxin kills T cells by pathways resembling necrosis and programmed cell death. Leukotoxin-induced lymphotoxicity may represent a critical mechanism by which A. actinomycetemcomitans suppresses the host local immune response and contributes to the pathogenesis of diseases involving this microorganisms. PMID- 1879941 TI - Killing of Plasmodium falciparum in vitro by nitric oxide derivatives. AB - We have investigated the in vitro susceptibility of the human malaria parasite Plasmodium falciparum to killing by nitric oxide and related molecules. A saturated solution of nitric oxide did not inhibit parasite growth, but two oxidation products of nitric oxide (nitrite and nitrate ions) were toxic to the parasite in millimolar concentrations. Nitrosothiol derivatives of cysteine and glutathione were found to be about a thousand times more active (50% growth inhibitory concentration, approximately 40 microM) than nitrite. PMID- 1879942 TI - Inhibitory effects of human salivary histatins and lysozyme on coaggregation between Porphyromonas gingivalis and Streptococcus mitis. AB - The effects of histatins on coaggregation between Porphyromonas gingivalis 381 and Streptococcus mitis ATCC 9811 were investigated by using a turbidimetric assay. The coaggregation activity was significantly inhibited by histatins 5 and 8 and strongly by lysozyme. Tritium-labeled histatin 8 bound to P. gingivalis cells but not to S. mitis cells. PMID- 1879943 TI - Growth of Francisella spp. in rodent macrophages. AB - We examined the nature of the interactions between the facultative intracellular pathogens Francisella tularensis and F. novicida and rodent macrophages. Growth of F. tularensis LVS was observed in macrophage monolayers from mice, guinea pigs, or rats. In contrast, F. novicida grew in macrophages from mice and guinea pigs but not in macrophages from rats. Transmission electron microscopy studies indicated that both Francisella species survive within macrophage phagosomes that are unfused with lysosomes. PMID- 1879944 TI - Pathogenicity of Candida albicans auxotrophic mutants in experimental infections. AB - Auxotrophic and prototrophic control strain pairs of Candida albicans constructed by molecular biology methodologies were evaluated for pathogenicity in a systemic mouse model. Mutants that were auxotrophic for adenine, uracil, and heme each showed a lowered level of pathogenicity relative to control strains. It can be concluded from these experiments that decreased pathogenicity in each case is due to the auxotrophic mutation, because mutant and control strains were constructed so as to differ at a single locus. These observations suggest that new therapeutic agents for Candida infections might be designed based upon the inhibition of biosynthetic pathways that, in some cases, might be absent from the host. PMID- 1879945 TI - Rat model of congenital toxoplasmosis. AB - A rat model of congenital toxoplasmosis is described for the study of protective immunity and chemotherapy during pregnancy. Six Sprague-Dawley 7- to 15-day gestational rats were inoculated orally (three rats, trial A) or subcutaneously (three rats, trial B) with 10,000 infective oocysts of the CT-1 strain of Toxoplasma gondii. The tissues of rat pups born from these rats were bioassayed for T. gondii infection. T. gondii was recovered from 30 of 33 (90.9%, trial B) and 23 of 28 (82.17%, trial A) rat pups bioassayed at 1 to 134 days of age. Two 10- to 14-day gestational pregnant rats were inoculated subcutaneously (trial C) with 10,000 infective bradyzoites from tissue cysts; 10 of 23 (43.8%) of the newborn pups were infected with T. gondii. Congenital infection occurred only when rats were infected during pregnancy. None of three rats in trial A that had given birth to congenitally infected rat pups produced congenitally infected rat pups during the second pregnancy. PMID- 1879946 TI - Protein and antigen heterogeneity among strains of Mycoplasma fermentans. AB - The proteins and antigens of three strains of Mycoplasma fermentans were compared with those of a mycoplasma, designated "Mycoplasma incognitus," recently identified in tissues of AIDS patients. Previous studies have shown that "M. incognitus" is most likely not a new species but rather a strain of M. fermentans. In the present study, one- and two-dimensional electrophoretic analysis demonstrated the expected similarity between these mycoplasmas, but it also demonstrated several distinct protein differences. Nine proteins were identified as strain variable by two-dimensional gel electrophoresis. Also, immunoblot analysis using rabbit antiserum against the type strain of M. fermentans (strain PG 18) documented the occurrence of size heterogeneity in at least one and possibly two other antigens. PMID- 1879947 TI - Blood proteins do not promote adherence of coagulase-negative staphylococci to biomaterials. AB - We studied the effects of in vitro and in vivo coating of catheters with human blood proteins on binding of coagulase-negative staphylococci. Coating resulted in no enhancement of binding. Catheters coated in vitro bound fewer organisms than uncoated catheters. Host proteins do not enhance adherence of coagulase negative staphylococci to biomaterials. PMID- 1879948 TI - Successive synovial Mycoplasma hominis isolates exhibit apparent antigenic variation. AB - The expression of surface proteins by 14 successive Mycoplasma hominis isolates obtained from the synovial fluid of a chronically infected septic arthritis patient was examined. Marked differences in the expression of surface proteins, as determined by monoclonal antibodies raised against the first isolate, were observed. However, identical restriction patterns and virtually identical hybridization patterns with probes containing the conserved genes of the Mycoplasma capricolum rRNA operon and the Escherichia coli elongation factor Tu suggest that the protein differences might reflect antigenic variation by M. hominis during infection. PMID- 1879949 TI - Distribution, expression, and long-range mapping of legiolysin gene (lly) specific DNA sequences in legionellae. AB - The legiolysin gene (lly) cloned from Legionella pneumophila Philadelphia 1 confers the phenotypes of hemolysis and browning of the culture medium. An internal lly-specific DNA probe was used in Southern hybridizations for the detection of lly-specific DNA in the genomes of legionellae and other gram negative pathogenic bacteria. Under conditions of high stringency, the lly DNA probe specifically reacted with DNA fragments from L. pneumophila isolates; by reducing stringency, hybridization was also observed for all other Legionella strains tested. No hybridization occurred with DNAs isolated from bacteria of other genera. The lly gene was mapped by pulsed-field gel electrophoresis to the respective genomic NotI fragments of Legionella isolates. By using antilegiolysin monospecific polyclonal antibodies in Western blots (immunoblots), Lly proteins could be detected only in L. pneumophila isolates. PMID- 1879950 TI - Purification and characterization of Helicobacter mustelae urease. AB - Helicobacter mustelae is a urease-rich bacterium associated with gastritis in ferrets. The ureases of H. mustelae and Helicobacter pylori, a bacterium implicated in human gastritis, share many characteristics. Helicobacter sp. ureases appear to be unique among bacterial enzymes in exhibiting submillimolar Km values and in being composed of two subunits. PMID- 1879951 TI - Intracellular microorganisms: a particular problem for chemotherapy. Introduction. PMID- 1879952 TI - Intracellular survival and expression of virulence determinants of Legionella pneumophila. AB - Legionella pneumophila, the causative agent of Legionnaires' disease is able to live and multiply within macrophages as well as within protozoan organisms. Legionella strains inhibit phagosome-lysosome fusion and phagosome acidification. By using two different cell culture systems, one derived from human macrophages and the other from human embryo lung fibroblastic cells, it is demonstrated that Legionella strains lose their virulence following cultivation in the laboratory. In order to study the mechanisms involved in intracellular survival of Legionella a genomic library of strain Legionella pneumophila Philadelphia I was established in Escherichia coli K-12. By cosmid cloning technique we were able to clone five putative virulence factors, two of which exhibit hemolytic activities and three of which represent membrane-associated proteins of 19, 26 and 60 kilodalton. One of the hemolytic proteins, termed legiolysin, represents a new toxin which specifically lyses human erythrocytes. The other hemolysin exhibits proteolytic properties in addition and is cytolytic for Vero and CHO cells. Further studies will be necessary to determine the exact role of the cloned proteins in the pathogenesis of Legionella. PMID- 1879953 TI - Microbial strategies for intracellular survival. AB - Not only viruses but also certain bacteria, fungi as well as protozoa are able to reside and multiply within host cells; some of these microorganisms are facultative, others obligate intracellular hosts. They differ from each other in their mode of entry and in their strategies to survive intracellularly. Some remain in the phagocytic vacuole where they either block the fusion of lysosomes or resist the attack of the acidic milieu as well as the enzymatic digestion and multiply. Others escape from the vacuole to the cytoplasm where they travel around. This implies that chemotherapy has to respect these various intracellular life cycles. Therefore an antibiotic treatment can only be effective when the drug arrives in an active form at the special site of microbial residence. PMID- 1879954 TI - Molecular architecture and dynamics of the plasma membrane lipid bilayer: the red blood cell as a model. AB - The structural backbone of the erythrocyte membrane, as well as that of any other plasma membrane, is provided by a lipid bilayer which is composed of more than 100 molecular species. The individual lipid classes are distributed over both halves of the bilayer in a highly asymmetric fashion: all glycolipids are exclusively confined to the outer membrane leaflet where we also find the majority of the two choline-containing phospholipids, sphingomyelin and phosphatidylcholine. The two amino-phospholipids are predominantly (phosphatidylethanolamine) or even exclusively (phosphatidylserine) localized in the cytoplasmic half of the bilayer. Glycolipids and sphingomyelin are not subject to transbilayer movements, a property that (under normal conditions) is shared by phosphatidylserine. Phosphatidylcholine exhibits a relatively slow transbilayer movement, revealing half-time values from 3 to 27 h, whereas phosphatidylethanolamine is subject to an ATP-dependent "flippase"-catalyzed inward movement with a half-time of approximately 30 min. Probably much faster than that of any other lipid, is the transbilayer movement of cholesterol, revealing a half-time value in the order of seconds. PMID- 1879955 TI - In vitro studies of endocytic membrane traffic. PMID- 1879956 TI - Activity of intracellular antibiotics. AB - We have studied the intracellular bioactivity of several antimicrobial agents against two strains of Staphylococcus aureus, a pathogen sequestrated in phagolysosomes, using peripheral blood neutrophils from human volunteers. This was compared to the activity of cell-associated drugs also measured in vitro. Several discrepancies (high cellular association, low bioactivity) were observed (coumermycin, glycopeptides, erythromycin and clindamycin) which can be due to the binding of the drug to a particular cellular organelle, to intracellular metabolization or inactivation, to unfavourable conditions in the phagolysosome (pH drop), or to a toxic effect of the drug on the functions of the neutrophil. Addition of the antibiotic during ingestion was frequently associated with better neutrophil-dependent killing through several potential mechanisms: coingestion of the antibiotic with the inoculum, modification of opsonization, release of activating substances and fragilization of the microorganism to oxygen-dependent or -independent killing mechanisms. PMID- 1879957 TI - Liposomes and nanoparticles as vehicles for antibiotics. AB - Colloidal drug carriers such as liposomes and nanoparticles are easily taken up by phagocytic cells and accumulate in the organs of the reticuloendothelial system. Therefore, they hold promise as carriers for the treatment of intracellular infections with antibiotics that would normally not find easy access to intracellular sites. Consequently, in in vitro and in vivo experiments the therapeutic efficacy of substances such as amphotericin B, dihydrostreptomycin, amikacin, ampicillin, stibogluconate against a number of microorganisms including Leishmania donovani, Candida albicans, Staphylococcus aureus, Mycobacterium avium, Listeria monocytogenes, and Salmonella typhimurium was increased significantly by binding to liposomes and nanoparticles. PMID- 1879959 TI - Seminal plasma immunosuppressive activity: the achilles heel of reproduction. PMID- 1879958 TI - Therapeutic activities of antibiotics in listeriosis. AB - In vitro practically all common antibiotics except cephalosporins are active against nearly all natural isolates of Listeria monocytogenes; the therapeutic efficacy of antibiotic treatment is, however, rather limited, since up to 30% listeriosis patients will succumb to this infection. At least one reason for this low in vivo efficiency is the intracellular habitat of L. monocytogenes. In animal experiments ampicillin or amoxicillin, respectively, are still the most active drugs. In addition, rifampicin also has pronounced protective activity. Coumermycin, which unfortunately cannot be given to humans, is the most reliable drug in animals. PMID- 1879960 TI - LDH and LDH-X activity in sperm from normospermic and oligozoospermic men. AB - Total lactate dehydrogenase (LDH) activity was measured in washed sperm from 74 oligozoospermic patients and 148 normospermic men. In the same samples, an additional iso-enzyme specific for germ cells, LDH-X was also measured. Both enzymatic activities were significantly higher in sperm from oligozoospermic patients than in those from normospermic men (P less than 0.001). In oligozoospermic patients, sperm LDH and LDH-X activities were related inversely to sperm concentration (r = -0.61 and r = -0.53, respectively). In normospermic men, this inverse relationship was less evident (r = -0.28 and r = -0.25, respectively). After separation of sperm on a discontinuous gradient of Percoll, LDH and LDH-X activities were increased in the non-migrated-sperm fractions and reduced in the migrated-sperm fractions in both groups of subjects when compared to the initial semen specimens. In addition, migrated sperm from oligozoospermic and normospermic men did not differ in their LDH and LDH-X activities. Although the possible contribution of immature germ-cells to these findings remains to be defined, the data suggest clearly that high levels of intracellular LDH and LDH-X are a biochemical feature of sperm from oligozoospermic subjects. PMID- 1879961 TI - An automated chemiluminescence test for diagnosis of leukocytospermia. AB - A new rapid and sensitive chemiluminescence (CL) test was developed for the analysis of leucocytes in semen. Opsonized zymosan induced luminol-dependent CL of diluted (1:500) semen was measured in samples from 64 fertile and infertile men with or without leukocytospermia, using an automated luminometer set-up. The white-blood-cell (WBC) count in semen was determined using a conventional leucocyte-peroxidase staining method. A good linear correlation (r = 0.932) was observed between the seminal white-blood-cell number and the CL response. The coefficients of inter-assay variations for the CL method were 9.6% and 1.8% for semen samples with 0.3 x 10(6) WBC ml-1 and 3.2 x 10(6) WBC ml-1, respectively. The results also suggest that the previously reported inhibitory effect of seminal plasma on CL activity of human phagocytes is due to the quenching of light-producing reactions and that this can be circumvented by using appropriate semen dilution. It is concluded that the simple and high-capacity CL test is an especially convenient method for routine diagnosis of leukocytospermia. PMID- 1879962 TI - 'Water-test': a simple method to assess sperm-membrane integrity. AB - The functional integrity of the membrane of sperm from semen samples collected from 10 fertile men (Group A) and from 50 infertile men (Group B) was assessed by studying the swelling reaction of sperm when suspended in a medium of distilled water ('Water-test'). The results were correlated with routine semen-analysis and with the results of Eosin-Y staining. The mean values for the 'Water-test' were significantly different (P less than 0.01) between Groups A and B (84.8 +/- 3.5 versus 70.9 +/- 13.3, respectively). No significant correlations were observed in either Group A or B, between values for the 'Water-test' and values for the sperm count, the percentage of sperm with normal morphology and the percentage of motile sperm. There was a good correlation in both Group A (r = 0.86, P less than 0.01) and Group B (r = 0.92, P less than 0.01) between values for the 'Water test' and those for the Eosin-Y test. These results indicate that the 'Water test' is a simple and reliable test for evaluating sperm membrane integrity. PMID- 1879963 TI - Effects of piperine on hamster sperm capacitation and fertilization in vitro. AB - The effect of piperine on the fertilizing ability of hamster sperm was investigated in vitro. Sperm were incubated in a capacitation medium for 3 h prior to co-incubation with hamster eggs in a fertilization medium for another 3 h. Addition of 0.18-1.05 mM piperine to the capacitation medium reduced both the percentage of eggs fertilized and the degree of polyspermia in a dose-dependent manner. When piperine was added to the fertilization medium alone, a significant reduction in fertilization was observed only at high doses (0.70-1.05 mM). The presence of piperine in the capacitation medium inhibited the acrosome reaction in a dose-dependent manner but had no effect on sperm motility, whether this was measured quantitatively or qualitatively. Piperine also inhibited the influx of calcium into sperm during capacitation. It is suggested that such an inhibition might be a major cause of a reduction of the acrosome reaction and the subsequent impairment of fertilizing ability of sperm. PMID- 1879964 TI - Serological discrimination between HTLV-I and HTLV-II antibodies by ELISA using synthetic peptides as antigens. AB - Using the peptides from amino acids 100-130 of the HTLV-I gag protein, 175-199 of the HTLV-I env protein and the corresponding peptides of HTLV-II (amino acids 106 to 135 of the gag protein and 171 to 196 of the env protein), we tested for reactivity against antibodies by enzyme immunoassay in sera from HTLV-I and HTLV II carriers. The peptides derived from the env proteins have high specificity for antibody binding. The peptide based on amino acids 175-199 of HTLV-I reacted with antibodies in sera from all HTLV-I carriers, and the peptide composed of amino acids 171-196 of HTLV-II reacted with antibodies in sera from all HTLV-II carriers. For the peptides derived from the gag proteins, we observed some cross reactivity in sera from persons with anti-HTLV-I and anti-HTLV-II, due to antibody binding to the peptide corresponding to 12 amino acids from the C terminal end of the gag protein. Separate enzyme immunoassays that used the four synthetic peptides as antigens clearly distinguished between serum with antibodies to HTLV-I or HTLV-II in various individuals and excluded false positive results using the particle agglutination assay that used a whole-virus lysate of HTLV-I as antigen. PMID- 1879965 TI - Incidence and prognostic significance of vascular invasion in 529 gastric-cancer patients. AB - The prognostic significance of blood-vessel invasion (BVI) and lymphatic-vessel invasion (LVI) was evaluated in a retrospective series of 529 gastric-cancer patients who underwent potentially curative surgery. Evidence for BVI was found in 127 patients (24.0%), while LVI was demonstrated in 245 patients (46.3%). The incidence of both BVI and LVI run parallel to increasing tumor size and tumor stage as well as to decreasing grade of tumor differentiation. The incidence of BVI and LVI was higher in lymph-node-positive patients than in lymph-node negative patients. The 5-year-survival rate was significantly lower (p less than 0.0001) in patients with BVI or LVI (14.9% and 22.2% respectively) than in patients without BVI or LVI (54.7% and 64.1% respectively). Both BVI and LVI were shown to be prognostic factors independent of tumor stage, grade of differentiation or lymph-node involvement. In a multivariate Cox regression analysis, the gain of prognostic information provided by the evidence of BVI and LVI was shown to exceed the information obtained by the combination of tumor stage, grade of differentiation and lymph-node involvement. A careful search for vascular invasion in gastric cancer may therefore provide additional useful information for identifying patients who are at high risk and who may be candidates for adjuvant therapy in future clinical trials. PMID- 1879966 TI - Leanness and lung-cancer risk. AB - Body mass index (weight/height2) was studied for its prediction of lung cancer in Finnish men examined by the Social Insurance Institution's Mobile Clinic and followed up by the Finnish Cancer Registry. Among 25,994 participants aged 20 to 75 years and free from cancer at the start of the study, 504 lung-cancer cases were diagnosed during a maximum follow-up of 19 years. There was a significant inverse gradient between body mass index and the incidence of lung cancer. This association was not due to confounding by age, smoking, social class, self perceived general health, history of stress symptoms, chronic cough or chest X ray findings, although these factors correlated with body mass index and were also significantly predictive of lung cancer. After adjustment for these factors, the relative risks of lung cancer were 1.0, 1.4, 1.5 and 1.8 (p for trend less than 0.001) from the highest to the lowest quartiles of body mass index. The association was noted among current smokers, but it was most obvious among men who had never smoked, the relative risk of lung cancer between the lowest and highest quartiles of body mass index being 7.6 (95% confidence interval = 2.0 to 29.4). The inverse gradient persisted throughout the entire follow-up period, and was most distinct after the first 10 years of follow-up, the relative risks for the quartiles of body mass index being 1.0, 1.9, 2.3 and 2.6 (p less than 0.001). The present study shows that the thinner the man, the more liable he is to develop lung cancer. Leanness or some factor or cluster of factors closely correlated to it, may play an aetiological role in lung cancer. PMID- 1879967 TI - Diet and bladder cancer in Spain: a multi-centre case-control study. AB - A multi-centre case-control study on bladder cancer and diet was carried out in 5 regions of Spain. We report results on 432 male cases and 792 matched controls. Usual dietary habits were investigated by means of an interview-based dietary history questionnaire. Bladder-cancer cases were selected from the registers of 12 hospitals located in the study areas. Each case was matched by sex, age and area of residence to 2 controls, one identified in the same hospital and one drawn from population lists. Descriptive analyses indicated that the average dietary pattern was typical of Mediterranean populations: a high P/S ratio, high intake of fish, fruits and vegetables and moderate or low intake of meat and dairy products. Relative risks for specific foods and nutrients were adjusted for tobacco smoking and energy intake. Subjects in the highest quarter of intake of saturated fat had a significantly increased risk of bladder cancer (RR for highest quarter = 2.25; 95% CI = 1.42 to 3.55). Moderate increases in risk for high intake of mono-unsaturated fats and calcium, and a slight decrease for iron were also found, but these disappeared after adjustment for saturated fat. Intake of vitamin E was related to slightly reduced risk (RR for highest quarter = 0.72; 95% CI = 0.48 to 1.09) which was not modified by adjustment for fat. No association was found with intake of retinol or carotene. These results, along with those of previous studies, suggest that saturated fat intake may influence the occurrence of bladder cancer. PMID- 1879968 TI - Differential susceptibility of BALB/c and DBA/2 cells to plasmacytoma induction in reciprocal chimeras. AB - Reciprocal chimeras were generated between BALB/c and DBA/2 mice by inoculating newborn recipients of either strain with bone-marrow (BM) cells of the other through the periorbital vein. DBA/2 mice inoculated with the BALB/c with proven chimerism will be referred to as C----D, the reciprocal as D----C. The BALB/c cells carried a Robertsonian 6;15 (Rb6;15) chromosome marker to facilitate identification. The chimeric mice contained between 5% and 70% of donor cells when examined at 4 to 5 weeks of age. Six of 10 C----D developed plasmacytomas (MPC) after 3 x 0.5 ml monthly pristane treatment (incidence 60%) and 8 of 25 (incidence 32%) after 2 to 3 x 0.5 ml pristane followed by Abelson virus (A-MuLV) infection. Seven of 15 D----C developed MPC after pristane treatment (incidence 47%) and 4 of 17 after pristane + A-MuLV (incidence 24%). All tumors that have arisen in both reciprocal chimeras originated from BALB/c cells independently of the degree of chimerism. All tumors contained an Ig/myc translocation. Among the C----D chimeras, 5 carried t(12;15) and I t(6;15) in the pristane-treated group, while 4 carried t(12;15), I t(6;15) and 3 t(15;16) in the pristane + A-MuLV. Among the D----C chimeras 6 carried t(12;15) and I t(6;15) in the pristane treated group, while 3 t(12;15) and I t(6;15) in the pristane + A-MuLV. No tumors developed in 18 pristane- and 22 pristane + A-MuLV-treated DBA/2 mice nor in 15 pristane- and 17 pristane + A-MuLV-treated (BALB/c x DBA/2)F1 mice. The data indicate that BALB/c and DBA/2 cells differ in their propensity to transform into plasmacytoma in identical host environments after both pristane and pristane + A MuLV treatment. They also show that the oil granuloma can support MPC development in either type of chimeric host. PMID- 1879969 TI - Establishment of an IL-2 independent, human T-cell line possessing only the p70 IL-2 receptor. AB - A continuous cell line was established from the blood of a patient (HH) with an aggressive cutaneous T-cell leukemia/lymphoma who lacked antibodies to human T lymphotrophic virus, type I. The immunophenotype of the cultured cells was CD2+, CD3+, CD4+, CD5+, CD8-, DR+ and CD25- (Tac, IL-2 receptor alpha chain). Southern blot hybridization analysis of T-cell-receptor beta chain DNA demonstrated the same rearrangement in freshly isolated blood cells and cultured cells, indicating that the cell line was derived from the patient's malignant clone. Since cultured T-cells grew in complete medium without added IL-2, we investigated whether HH cells could be producing and responding to IL-2 in an autocrine fashion. However, no IL-2 was detectable in supernatant from the cell line, while antibodies to IL 2, or to the IL-2 receptor alpha or beta chains did not inhibit cell growth. In addition, no mRNA message for IL-2 was detectable in these cells. The results appear to exclude an autocrine IL-2-dependent mechanism of cell growth for this T cell line. Although cultured HH cells lacked detectable IL-2 receptor alpha chain, they did show increased proliferation to exogenous IL-2. Binding studies with 125I-IL-2 demonstrated an intermediate affinity receptor for IL-2, KD = 1.7 nM, with 6400 binding sites per cell, suggesting the presence of an IL-2 receptor beta chain. Consistent with these findings 125I-IL-2 cross-linking studies demonstrated a single receptor calculated to be 75 kDa. Also, the beta chain of the IL-2 receptor was detected by immunofluorescence using specific monoclonal antibodies (MAbs). Nanomolar concentrations of an IL-2-diphtheria toxin fusion protein inhibited cellular protein synthesis, an effect abrogated by native IL-2. These findings indicate that the IL-2 receptor beta-chain was functional. This novel mature T-cell line may be useful in studies of IL-2 receptor regulation and in analysis of the mechanism of T-cell leukemogenesis. PMID- 1879970 TI - Selective induction of endothelial cell tissue factor in the presence of a tumour derived mediator: a potential mechanism of flavone acetic acid action in tumour vasculature. AB - Flavone acetic acid (FAA) is a potentially useful anti-tumour agent which has been reported to induce changes in tumour vasculature, in particular loss of bloodflow. This led us to examine whether endothelium could be a cellular target of FAA action, with resultant modulation of cell-surface coagulant properties leading to activation of coagulation and blockade of tumour blood flow. Incubation of endothelium with FAA led to the expression of functional tissue factor on the cell surface, in a time-dependent and dose-dependent (half-maximal at 0.6-0.7 mg/ml) manner. Induction of tissue-factor activity resulted from de novo translation of the tissue factor message. To explain the selectivity of FAA's action on tumour vasculature in vivo, we considered its interaction with tumour-derived factors. Starting with serum-free FO-I-melanoma cell-conditioned medium, a co-factor enhancing FAA-mediated induction of endothelial tissue factor (FO-I factor) was partially purified by sequential ion exchange and reverse phase chromatography, followed by preparative SDS-PAGE. The FO-I factor migrates with an apparent Mr of approx. 20 to 25,000 on non-reduced SDS-PAGE, is sensitive to protease K, and augments the effect of FAA on endothelial-cell-tissue factor. This activity is not found in supernatants from non-neoplastically transformed cell lines. These data lead us to hypothesize that FAA exerts its action, at least in part, by promoting activation of coagulation on the endothelial surface, and this effect is selective for the tumour bed by virtue of its interaction with a tumour-derived factor. The interaction of FAA with host factors may be important for optimizing its therapeutic efficacy for a particular tumour. PMID- 1879971 TI - Synergistic anti-tumor effects of combined IL-1/IFN-alpha/beta therapy in mice injected with metastatic Friend erythroleukemia cells. AB - Peritumoral injection of relatively low doses of either mouse interferon (IFN) alpha/beta (10,000-20,000 units/injection) or of recombinant human interleukin-1 (IL-1) beta (125-250 ng/injection) in mice transplanted s.c. with Friend erythroleukemia cells (FLC) resulted in some inhibition of primary tumor growth, inhibition of liver and splenic metastases and increased survival time. A synergistic anti-tumor effect was observed in mice injected with both IL-1 and IFN-alpha/beta. Highly purified mouse IFN-beta also exerted a synergistic anti tumor effect when combined with IL-1-beta in mice injected with FLC. The anti tumor action of IL-1/IFN was markedly reduced in mice treated with antibodies to CD4 antigens. Antibodies to asialo-GM1 also diminished the anti-tumor effect by the combined cytokine treatment. The combined IL-1/IFN therapy was effective in NK-deficient bg/bg mice, although the extent of the anti-tumor response in these mice was less than that observed in bg/+mice. PMID- 1879972 TI - Subcellular localization, redistribution and photobleaching of sulfonated aluminum phthalocyanines in a human melanoma cell line. AB - Intracellular localization, intracellular translocation and photobleaching following non-lethal laser microirradiation of the fluorescing derivatives of sulfonated aluminum phthalocyanines (Al-PcSn, n = 1-4) in a human melanoma cell line (LOX) were studied by means of confocal laser scanning microscopy (LSM) and image processing. Use of confocal microscopy allowed 3-dimensional information to be obtained. Both Al-PcS1 and Al-PcS2 localized diffusely in the cytoplasm of the cells, while Al-PcS3 and Al-PcS4 exhibited a granular pattern in the extranuclear fraction of the cells. None of the Al-PcSn family was observed in the nuclei of the cells except that a small fraction of fluorescence was occasionally detected in nuclei of some cells treated with Al-PcS1 and Al-PcS2. Furthermore, exactly the same granular localization patterns and positions in the same cells were found after incubation initially with Al-PcS3 (or Al-PcS4) followed by acridine orange (AO) which emits red fluorescence from lysosomes of cells. Thus, the granular fluorescence of Al-PcS3 and Al-PcS4 is confined to the lysosomes of the LOX cells. Non-lethal laser exposure of cells incubated with high concentrations of the 2 dyes resulted in a translocation of the dyes from the lysosomes to the whole cytoplasm and an increase in total intracellular fluorescence intensity. Finally, a small fraction of the dyes localized into the nuclei of the cells. The laser exposure of cells incubated with low concentrations of the lysosomally localized dyes resulted in an increase in the intracellular fluorescence intensity with no translocation of the dyes. Under all conditions, high laser exposure resulted in a decrease in the total intracellular fluorescence intensity. PMID- 1879973 TI - Tumoricidal alveolar macrophage and tumor infiltrating macrophage cell lines. AB - Continuous alveolar macrophage (AM) and tumor-infiltrated (TIM) cell lines have been generated from C57B16J mice by in vitro infection with the J2 retrovirus carrying the v-raf and v-myc oncogens. Four cloned AM cell lines (AMJ2-C8, AMJ2 C10, AMJ2-C11, AMJ2-C20) and 3 cloned TIM cell lines (TIMJ2-C4, TIMJ2-C7 and TIMJ2-C15) were expanded for further characterization. Flow cytometry detected the product of the raf gene in the cytoplasm of all these cell lines. Studies on the tumoricidal properties of these AM and TIM cell lines demonstrated differences in their response to a panel of known macrophage activators. Four of these cell lines (AMJ2-C8, AMJ2-C10, TIMJ2-C7 and TIMJ2-C15) were activated following exposure to recombinant murine interferon gamma (rMuIFN-gamma) but not lipopolysaccharide (LPS) or muramyl dipeptide (MDP). AMJ2-C20 was only activated by incubation with rMuIFN-gamma plus LPS. AMJ2-C11 and TIMJ2-C4 are the cell lines that most closely resembled the response pattern of the parental AM and TIM, since they could be activated by either the combination of rMuIFN-gamma plus LPS or rMuIFN-gamma plus MDP. Constitutive expression of MHC-class-II antigens was low on AMJ2-C11 or TIMJ2-C4 but was increased following exposure to rMuIFN gamma. Neither cell line secreted substantial amounts of IL-1 or TNF but both secreted large amounts of IL-6. Thus these cell lines could be powerful tools to study AM and TIM activation and cytotoxicity. PMID- 1879974 TI - Survival of leukemic cells in a dormant state following cyclophosphamide-induced cure of strongly immunogenic mouse leukemia (DL811). AB - The B-cell leukemia line, DL811, established in DDD mice, has been characterized by strong immunogenicity leading to occasional spontaneous cure with tumor dormancy. Cyclophosphamide (CY) is an available chemo-immunotherapeutic agent. The effects of CY on the cure and dormancy of DL811 leukemias were investigated. Simultaneous injection of DL811 cells and CY into athymic nude mice revealed that DL811 cells were sensitive to CY doses of 0.5 mg and more per mouse in a dose related manner. A single dose of 1 mg CY on day 7 after DL811 cell inoculation was most curative of disseminated leukemias (cure rate: 50-80%) as compared with other single CY doses at different times. Cured mice were strongly immune to DL811 leukemias. This therapeutic modality had no curative effect in athymic nude mice. Relapses occurred occasionally in CY-cured mice and most relapsed tumors had the same surface phenotype as that of the DL811 leukemia. In comparison with DL811 leukemias, however, relapsed tumors were less sensitive to rejection by cured mice and less frequently cured by a single dose of 1 mg CY on day 7 of inoculation, implying that they changed in antigenicity and drug sensitivity. Whole-body irradiation of 400 rad gamma-rays to cured mice raised the incidence of relapses from 22.9 to 44.7% and that of deaths from relapses from 8.6 to 26.3%. Thus, leukemic cells may survive against host immune surveillance in a dormant state and relapse after changing their immunologic and chemotherapeutic natures. Lyt-2+, L3T4- T cells appeared to mediate host anti-tumor immunity to eradicate leukemic cells and maintain dormant state. PMID- 1879975 TI - Spontaneous rosetting of human T lymphocytes with breast cancer cells. PMID- 1879976 TI - Whither paediatric cardiology? PMID- 1879977 TI - Double-blind randomised placebo-controlled dose-efficacy study of sustained release verapamil in chronic stable angina. AB - The efficacy and tolerability of sustained release verapamil (Securon SR) was investigated in twenty-four patients with chronic stable angina. Patients entered four randomised, double-blind treatment periods, each lasting one week of verapamil-SR 240 mg once daily, 360 mg once daily, 240 mg twice daily, and matching placebo. Four patients were withdrawn, but in one instance this was attributable to side effects from verapamil. Among the remaining twenty patients, mean frequency of angina fell from 4.25 episodes during the last five days of placebo to 2.35, 2.6 and 1.3 episodes during respective active treatments (all P less than 0.001). Compared with placebo the median percentage increase in time to 1 mV ST depression during treadmill exercise (12 hours post dose) was significant only with the regimen of verapamil-SR 240 mg given twice daily at +11% (P = 0.04). Total duration of exercise was also significantly longer and maximum ST depression significantly less only with the twice daily treatment (704 + 186 sec vs 648 + 203 sec; P = 0.03, and 1.75 + 0.73 mm vs 2.15 +/- 0.62 mm; P = 0.02). Side effects, predominantly constipation, breathlessness, and swollen ankles, occurred most frequently with verapamil-SR 360 mg. Thus, sustained release verapamil is well tolerated and effective in the treatment of angina. A regimen of 240 mg given twice daily emerges as superior to once daily treatments for 24 hour prophylaxis of angina. PMID- 1879978 TI - First dose hypotension with enalapril and prazosin in congestive heart failure. AB - Since the introduction of angiotensin converting enzyme inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the angiotensin converting enzyme inhibitor enalapril a multicenter, open, randomized, prazosin-controlled trial was designed comparing the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 mg prazosin. Subjects were 1210 inpatients with New York Heart Association functional class (I)/II and III who were not adequately compensated with digitalis and/or diuretics. In the group receiving enalapril, 3 patients (0.5%) experienced severe hypotension on day 1 and 28 patients (4.7%) moderate hypotension. In those given prazosin, 15 patients (2.6%) experienced severe hypotension and 60 patients (10.3%) moderate hypotension. The difference is statistically significant (P less than or equal to 0.000012). All patients recovered. It was concluded that treatment of patients suffering from congestive heart failure New York Heart Association functional class (I)/II or III with enalapril is comparably well tolerated. PMID- 1879979 TI - Association between cigarette smoking and coronary arterial disease in patients in India: how quantitative is it? An assessment by selective coronary arteriography. AB - With a view to study the association between smoking and coronary arterial disease, and to identify any quantitative relationship, we undertook a cross sectional analysis of 1105 consecutive male patients investigated by selective coronary arteriography to confirm or exclude coronary arterial disease. Pattern and distribution of disease were evaluated in 3 groups of patients who never smoked; who smoked less than 5 cigarettes per day; and who smoked 6 to 60 or more cigarettes per day. Suitable statistical tests, including adjusting for confounders, were carried out. The prevalence of disease was higher amongst smokers even after adjustment for confounders. The number of cigarettes smoked, and whether the smokers had quit, made no difference to the angiographic appearance or extent of disease. There was no difference in the distribution and severity of disease amongst smokers and non-smokers. Rate ratio of disease amongst smokers in India was higher in those patients between 26 and 45 years of age than in other age groups. Smoking could be identified as a risk marker/risk factor that accelerated the disease process in those prone to develop the disease. It may be advantageous to initiate public health and preventive measures directed specifically at the group aged between 26 to 45 years, and later to address all others who smoke. PMID- 1879980 TI - Electropharmacological effects of sandostatin in human atrial fibers. AB - We studied the actions of sandostatin (0.1-1000 nM), an analogue of somatostatin, on human atrial tissues obtained from hearts of 20 patients undergoing corrective cardiac surgery. In 3 preparations showing fast response action potential in normal [K]0 Tyrode solution, sandostatin induced little effect, even at the highest concentration (1 microM). In 10 preparations showing a slow rate of phase 0 depolarization when atrial fibers were depolarized (maximum diastolic potential near -40 mV) in high [K]0 (27 mM), sandostatin at concentrations as low as 1 nM decreased significantly the velocity of the upstroke, and the amplitude of slow response of the action potential as well as the force of contraction. In 6 experiments on spontaneously active atrial fibers (maximum diastolic potential = 53.8 +/- 2.7 mV), sandostatin increased the spontaneous cycle length in a fashion dependent upon concentration. The decrease in spontaneous rate of firing was associated with an inhibition of the late diastolic slope, a change also induced by somatostatin. A longer period of washout, however, (30 min or longer) was required for complete recovery from the depressant effects. Sandostatin (0.1-100 nM) also depressed triggered activity induced by cardiotonic agents. The present findings indicate that sandostatin induces a prolonged action in human atrial cells. Sandostatin may depress abnormal automatic rhythms through an inhibition of transmembrane influx of calcium. PMID- 1879981 TI - Constrictive pericarditis versus restrictive cardiomyopathy: the role of Doppler echocardiography in differential diagnosis. AB - Doppler ultrasound recordings of velocities of flow across the mitral and tricuspid valves and in the hepatic veins, and their variation with respiration, were recorded in seven patients with constrictive pericarditis and in six patients with restrictive cardiomyopathy. Deceleration of mitral and tricuspid flow was also evaluated during apnea. Color flow Doppler was performed in order to evaluate mitral and tricuspid regurgitation. Eight healthy adults served as controls. The patients with constrictive pericarditis showed higher peak diastolic velocities of mitral flow, as well as marked increase of velocity of flow at the onset of expiration and decrease at the onset of inspiration. Reciprocal respiratory variation of the velocities were also observed across the tricuspid valve. The patients with restrictive cardiomyopathy showed moderate or severe mitral and tricuspid regurgitation. They also showed shorter deceleration of flow across the mitral and tricuspid valves during apnea. The pattern of flow in the hepatic veins showed reversal during systole with accentuated reversion during inspiration. These results suggest that patient with constrictive pericarditis and restrictive cardiomyopathy can be differentiated by comparing Doppler echocardiographic data, along with changes induced by respiration. PMID- 1879982 TI - Morphometric data on the arterial duct in the human fetal heart. AB - In a total of 496 fetuses and newborns ranging in body weight from 60 to 5000 g, we performed a morphometric study of the ascending aorta, the descending aorta, the aortic isthmus, the right pulmonary artery, the left pulmonary artery and the arterial duct. In all, nine different parameters were measured in each specimen. The variations in the correlations between two measurable characteristics, namely body weight and each of the morphometric parameters, were analyzed. The minimum, normal and maximum patterns of normality for each parameter were obtained with regression equations. We compared statistically the diameter of the arterial duct with the diameter of the ascending and descending aorta, the aortic isthmus, the right pulmonary artery and the left pulmonary artery with one way analysis of variance, using Bonferroni's test in the pairwise comparisons. The diameter of the arterial duct was smaller than the diameter of the ascending and descending aortas, the aortic isthmus, the right pulmonary artery and the left pulmonary artery, and the diameter of the ascending aorta was larger than that of the descending aorta. These morphological data have immediate clinical and surgical applications in the treatment of fetal and perinatal cardiovascular disorders. PMID- 1879983 TI - Conduction disturbances induced by postural changes. AB - We report two patients in whom postural changes induced arrhythmias. The first is a 70-year-old patient in whom leg flexion caused severe bradycardia. The second is a patient of 42 in whom standing up abruptly caused ventricular tachycardia. The importance of considering the possibility of posturally induced arrhythmias is emphasised when symptoms suggestive of arrhythmia are found and conventional measures fail to disclose any pathology. PMID- 1879984 TI - Asymptomatic eosinophilic myocarditis: 2 + 2 = 4 or 5! AB - A twenty-eight year old man was admitted with a cerebrovascular accident and hypereosinophilia secondary to microfilarial infection. Endomyocardial biopsy revealed focal eosinophilic myocarditis. The intriguing presence of this asymptomatic myocarditis raises interesting possibilities. PMID- 1879985 TI - Feasibility of emergency surgery for the treatment of an echocardiographically detected right atrial thrombus in a patient over 80 years of age presenting with shock. AB - We report the case of an 83-year old woman, presenting with progressive shock, in whom a right atrial thrombus was diagnosed by cross-sectional echocardiography. Doppler echocardiography demonstrated diastolic interruption of tricuspid inflow. Emergency thrombectomy was successful and without major complications despite the advanced age. PMID- 1879986 TI - Spontaneous left atrial haematoma. AB - We present a woman with paroxysmal atrial fibrillation and a mass in the left atrium. Cross-sectional echocardiography defined the lesion as cystic, while magnetic resonance imaging depicted it as a solid mass with areas of focal bleeding. Surgical resection showed a partially organized haematoma within the left atrial wall. The patient did well after surgery, although atrial fibrillation recurred. The presence of an atrial haematoma is rare, specially when spontaneous, and we stress the usefulness of magnetic resonance in reaching an aetiologic diagnosis. PMID- 1879987 TI - Filling of multiple vessels by injection of dye into a single bypass graft. AB - We describe the unusual filling of two coronary bypass grafts by a single injection in a patient who underwent coronary arterial bypasses surgery. The injection, made in the left internal mammary artery, filled the left anterior descending artery, a diagonal branch, and the graft of saphenous vein placed to that artery. In contrast, injection in the saphenous vein graft to the diagonal artery filled the diagonal artery, the left anterior descending artery and the left internal mammary to its point of origin. We emphasize the importance of this phenomenon. PMID- 1879988 TI - Syncope induced by propranolol in hypertrophic cardiomyopathy. AB - A patient with chest pain was found to have obstructive hypertrophic cardiomyopathy. After the first oral dose of propranolol, syncope developed together with atrioventricular block. An electrophysiologic study revealed an intermittent advanced (His-Purkinje) block within the atrioventricular conduction system. Caution is recommended when treatment is initiated in patients with hypertrophic cardiomyopathy in whom there is any suspicion of abnormalities in the atrioventricular conduction tissues. PMID- 1879989 TI - Competitive interactions of drugs with their targets: a computerized improvement of Dixon's algorithm. AB - Many drugs are competitive and reversible enzyme inhibitors. When the target enzyme kinetics follows the Michaelis-Menten equation, the enzyme affinity of the inhibitor is characterized by a single parameter: the Ki value. This parameter is usually determined via Dixon's procedure: (i). the rate of reaction (V) is measured in the presence of a few concentrations of the inhibitor (I); (ii.) 1/V versus I gives a straight line, which allows a graphic determination of the inhibitory constants, or better via a least-square fit the linear regression. The introduction of appropriate weighting factors in the linear regression may improve the accuracy of the Ki determinations. PMID- 1879990 TI - Effect and pharmacokinetics of netilmicin given as bolus intramuscular administration: an open comparative trial versus amikacin and fosfomycin in elderly patients affected by urinary tract infections. AB - A randomized comparative open clinical trial was performed on 96 hospitalized patients of both sexes, most of whom (84.4%) over 60 years of age, affected by simple and complicated urinary tract infections. Patients were divided in three unequal sized groups and treated with a single administration of netilmicin (5 mg/kg intramuscularly), of amikacin (15 mg/kg i.m.) or of fosfomycin (3 g per os). Patients were evaluated clinically and microbiologically before the beginning of the therapy, 1, 7, 15, 30 days thereafter and at monthly intervals, up to the 18th month, after the drug administration. The pharmacokinetic study was performed in six elderly patients of both sexes, apparently in good general health, except for their urinary tract infections. Symptoms of urinary tract infection disappeared in 50 out of 53 (94.3%) patients treated with netilmicin 14.48 +/- 9.6 hours after the drug administration, in 22 out of 23 (95.6%) of those treated with amikacin after 31.9 +/- 14.3 hours and in 16 (84.2%) out of 19 of symptomatic patients treated with fosfomycin after 37.5 +/- 10.6 hours. The disappearance of symptoms in netilmicin-treated patients is significantly (p less than 0.01) faster than in the other two groups. Twenty-four hours after the administration, netilmicin and amikacin produced sterilization of the cultures in more than 95% of cases, fosfomycin in 90%. Of those patients in which sterilization of cultures was achieved about 70%, in the netilmicin group, and 50% in the other two treatment groups had sterile urine cultures after one month. At the end of the study, 18 months later, more than 60% of the patients treated with netilmicin, the infection had not recurred in comparison with 39.1% and 50% in the amikacin and fosfomycin groups respectively. If only the patients with uncomplicated infections were considered, 88.9% and 83.3% had sterile cultures after 1 and 18 months respectively in the netilmicin group. The corresponding figures in other two groups were: 66.7% for both time intervals in the case of amikacin and 60% both for 1 and 18 months in the case of fosfomycin. The pharmacokinetic results indicate that netilmicin is rapidly absorbed and distributed from the injection site, possesses a beta half-life of about two hours and is mainly excreted by the kidneys. The single dose administration produces very high urinary concentrations of the drug in the first 24 hours and concentrations above 4 micrograms/ml, the 90% minimum inhibitory concentration cut-off point for netilmicin sensitive strains, for four days(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1879991 TI - Chronotherapeutic study of furosemide in hypertensive subjects: a preliminary report. AB - In the present study, circadian influences of furosemide on serum electrolytes, lipids and glucose were evaluated in ten hypertensive subjects. A retard capsule (40 mg) of furosemide was given once a day in the morning (07 h 00) or in the evening (19 h 00) for eight weeks. The study was done through a cross-over design. Twenty-four hour urine was collected, and fasting blood samples were obtained during the control period and at the end of each treatment period. The 24-hour urine volume was slightly increased by the repeated administration of furosemide in the morning and evening trials. Urinary excretion of sodium also slightly increased in the morning trial and significantly increased in the evening trial. Serum concentrations of potassium and chloride decreased, while serum uric acid and triglyceride were increased by furosemide treatment. No significant difference was observed in these parameters between morning and evening trials. Fasting blood glucose increased following furosemide. The increment in this parameter was greater in the evening trial than in the morning trial. These findings indicated that the influence of furosemide on glucose tolerance might vary with its time of administration. PMID- 1879992 TI - Influence of acetyl-L-carnitine infusion on haemodynamic parameters and survival of circulatory-shock patients. AB - The clinical use of acetyl carnitine in circulatory shock has its theoretical basis in the ability of this molecule to restore enzyme activity inhibited by hypoxia, acting as an acetyl donor. Moreover the action of carnitine on an injured myocardium encouraged us to examine the clinical effect of this drug during heart failure. A double-blind clinical study was performed in ten Italian intensive care units on 115 patients with septic, cardiac of traumatic shock, by using acetyl-L-carnitine infusion for 12 hours, with a previous single bolus intravenously. The results showed a good response to the drug in terms of blood oxygenation during the course of sepsis and heart failure. The heart rate as well as right atrial pressure decreased significantly in patients with cardiogenic shock. In septic patients systolic and mean arterial pressures increased also. The present data suggests the use of acetyl-L-carnitine as an adjuvant to the commonly used therapy in hypoxic conditions. PMID- 1879993 TI - Plasma morphine and morphine-6-glucuronide patterns in cancer patients after oral, subcutaneous, sublabial and rectal short-term administration. AB - Clinical studies on the effectiveness of morphine administered through different routes are contradictory. In order to further elucidate this point, the plasma concentrations of morphine and its 3- and 6-glucuronated metabolites were measured after short-term oral, sublabial, rectal and subcutaneous administration of the opiate. The bioavailability of free morphine and the 6-glucuronated active metabolite was comparable through the different routes. It was concluded that the choice of the route of morphine administration should be mainly guided by the needs of each individual patient. PMID- 1879994 TI - Dapiprazole compared with clonidine and a placebo in detoxification of opiate addicts. AB - The activity of dapiprazole, clonidine and a placebo were studied to reduce abstinence symptoms and modify the psychological outline during a withdrawal period in heroin addicts. Forty heroin addicts were treated in a double-blind design and, within two weeks, relapse in heroin use was higher in the placebo group (8/10) in comparison with the dapiprazole (1/20) and clonidine (0/10) groups. During treatment clonidine was able to reduce depression and paranoid ideas scores, whereas dapiprazole reduced depression, anxiety, hostility, phobic anxiety, obsessiveness and psychoticism. Side-effects were mild and it may be concluded that both dapiprazole and clonidine are effective and safe drugs for the treatment of opiate withdrawal syndrome. PMID- 1879995 TI - Systemic associations of retinal arterial obstructive disease. PMID- 1879996 TI - Systemic association of ocular disorders. PMID- 1879997 TI - Systemic associations of anterior uveitis. PMID- 1879998 TI - Systemic associations of exophthalmos. PMID- 1879999 TI - Systemic associations of retinal vein occlusion. PMID- 1880000 TI - Systemic associations of optic neuritis. PMID- 1880001 TI - Systemic associations of pigmentary retinopathy. PMID- 1880002 TI - Systemic associations of angioid streaks. PMID- 1880003 TI - Systemic associations of dry-eye syndrome. PMID- 1880004 TI - Systemic associations of corneal deposits. PMID- 1880005 TI - Genomic imprinting and nuclear totipotency during embryonic development. PMID- 1880006 TI - Molecular anatomy of the blood-brain barrier as defined by immunocytochemistry. AB - This review outlines the recent developments and improvements of our knowledge concerning the molecular composition of the BBB as revealed by immunocytochemistry. Data have been accumulated which show that the BBB exhibits a specific collection of structural and metabolic properties which are also found in tight transporting epithelia. This conclusion is substantiated by (i) the implementation of antibodies which recognize proteins of non-BBB origin, to show that these biochemical markers and the functions that they represent are localized in the BBB endothelium; and (ii) the characterization of target molecules to which polyclonal or monoclonal antibodies which have been generated to epitopes of the BBB endothelium or brain homogenates. According to these data the protein assemblies comprising the phenotypical appearance of the BBB can therefore be defined by the particular selection as well as topological expression of common epithelial antigens, rather than the expression of BBB unique molecular species. In this respect the immunocytochemical data corroborate the physiological assumption that the BBB possesses the character of a specific polarized epithelium. Attention is also given to the description of developmental expression of BBB-related immunomarkers. By collecting the data from different sources we introduce a classification of the BBB marker proteins according to their developmental appearance. Three groups of proteins are classified with respect to their sequential expression around the time of BBB closure: Phase E (early) markers which appear before BBB closure, phase I (intermediate) markers which are expressed at the time of BBB tightening, and phase L (late) markers which are detectable after the closure of the BBB. Such a scheme may to be useful in better defining the maturation process of BBB, which apparently is not a momentary event in brain development, but rather consists of a temporally sequenced process of hierarchically structured gene expression which finally define the molecular properties of the BBB. This process continues even after parturition, especially with regard to the achievement of immunological properties of the mature BBB. By examining the developmental spatio-temporal expression of different BBB markers we conclude that the mechanisms governing the pattern of BBB maturation are not limited to the interactions occurring between glial and endothelial cells. We therefore suggest a heuristic model in a triangular interrelationship that includes differentiation effects of neurons on glia and of glia cells on the BBB endothelium.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1880007 TI - [Does internal medicine still exist today?]. PMID- 1880008 TI - [Ambulatory medical care in Germany]. PMID- 1880009 TI - [Lower gastrointestinal hemorrhage]. PMID- 1880010 TI - [Epidemiology of colorectal cancers]. PMID- 1880011 TI - [Colorectal cancer--diagnosis, early detection and staging]. PMID- 1880012 TI - [Limits of endoscopic management of malignant colorectal polyps]. PMID- 1880013 TI - [Chemo- and immunotherapy of colorectal cancer]. PMID- 1880014 TI - [Excessive hypertriglyceridemia and pancreatitis in a 17-year-old pregnant patient]. PMID- 1880016 TI - Meeting of the Membranes Group of the Italian Biochemical Society. June 1-2, 1990, Ancona. Abstracts. PMID- 1880015 TI - [Traumatically-induced aneurysm of the arteria lienalis]. PMID- 1880017 TI - Meeting of the Silica Group of the Italian Biochemistry Society. April 27, 1990, Catania. Abstracts. PMID- 1880018 TI - The role of monocytes and T cells in 1,25-dihydroxyvitamin D3 mediated inhibition of B cell function in vitro. AB - 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) inhibits immunoglobulin production by human mononuclear cells (MNC) in vitro. The present study was undertaken to evaluate the role of T cells and monocytes in 1,25-(OH)2D3 induced suppression of B cell functions. The synthetic vitamin D3 analogue MC 903 was examined in parallel. 1,25-(OH)2D3 and MC 903 showed a dose-related inhibition of IgM, IgG and IgA plaque-forming cells in poke-weed mitogen (PWM) activated cultures of MNC. This effect was most likely mediated through impairment of T cell and monocyte functions. First, the inhibitory effect was seen after PWM stimulation, but not after Epstein-Barr virus stimulation which activates B cells independently of T cells and monocytes. Second, 1,25-(OH)2D3 was not effective in T cell and monocyte-depleted cultures. Third, the effect of 1,25-(OH)2D3 on PWM driven MNC was reversed by addition of the recombinant monokines: interleukin (IL)-1 beta, tumour necrosis factor alpha (rTNF alpha), rIL-6, as well as the lymphokines: lymphotoxin (rLT) and rIL-2. This is consistent with the finding that 1,25-(OH)2D3 also inhibited IL-1 alpha, TNF alpha and LT production in these cultures. The assumption that B cells are not directly affected by 1,25-(OH)2D3 was further supported by the fact that 24 h of culture with 10(-8) M 1,25-(OH)2D3 failed to reduce immunoglobulin production by in vivo activated B cells. PMID- 1880019 TI - Structure/function studies of T-2 mycotoxin with a monoclonal antibody. AB - A BALB/C murine monoclonal antibody (mAb) specific for the trichothecene mycotoxin T-2 was previously generated. The anti-T-2 antibody, designated HD11, can detect T-2 in the nanogram range employing an enzyme-linked immuno-sorbent assay. The HD11 antibody at a concentration of 1 microgram/ml completely protected against the T-2-induced cytotoxicity of the human epidermoid carcinoma cell lines Hep-2 and KB. Fine specificity analysis was performed using 10 structurally related T-2 metabolites to inhibit the specific binding of HD11 to T 2 mycotoxin. The results suggest a binding specificity of the protective HD11 antibody for the bulky hydrophobic alkyl side chain at position R5 and the acetyl groups at positions R2 and R3 of the T-2 mycotoxin molecule. HD11 anti-T-2 mAb, which bound to the T-2 metabolite acetyl T-2 (with a substituted acetyl group at R1 position), efficiently neutralized its in vitro cytotoxicity. On the other hand, the cytotoxicity of T-2 metabolites neosalaniol and 3' OH HT-2, both of which lack the alkyl side chain at position R5 and which did not bind to HD11, was unaffected by HD11. PMID- 1880020 TI - Toxicological and immunological evaluation of the immunosuppressant 15 deoxyspergualin in BALB/c mice: an in vivo and in vitro study. AB - The toxicological aspects as well as the immunosuppressive mechanism of 15 deoxyspergualin (DSP) were studied using BALB/c mice. Five-week-old animals were subcutaneously given phosphate-buffered saline (PBS; Group 1) or DSP at 0.5 (Group 2) to 5.0 mg (Group 4) per kg body weight daily for 1 to 3 months. They were sacrificed to obtain blood for hematology and liver function studies. The spleen, taken simultaneously, was histologically examined, the T cell surface markers of splenocytes were flow cytometrically measured, and their interleukin 2 (IL-2) production induced in vitro by Enterotoxin A (Ent A) was assayed using CTLL cells. Additionally, the in vitro effect of DSP on IL-2 generation and plaque forming cell (PFC) production was studied using splenocytes of non-treated mice. During the 3 months of treatment, the body weight slowly increased in Groups 1 and 2, while the body weight of the 2.5-mg DSP mouse group (Group 3) was significantly lower on days 28 and 56 of treatment compared with Group 1 of the same age (P less than 0.05). The administration of DSP at 5.0 mg/kg (Group 4) caused marked reduction in body weight of the animals. They were sacrificed on day 28 because of their worsening general condition. WBC and RBC counts decreased in Group 3 on days 57 and 93, and the platelet number increased on day 57. A liver function test was not affected by DSP treatment except for an elevated SGOT in Group 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880021 TI - Determining optimal protective actions for nuclear incidents. AB - The U.S. Environmental Protection Agency is revising its Protective Action Guides (PAGs), which specify recommended dose levels at which actions should be taken to protect the public during an accident at a nuclear facility. The appropriateness of these PAGs depends on the health risks that could be avoided by the protective actions relative to both the costs and adverse health impacts of taking the actions. According to the optimization principle of radiation protection, the cost of measures designed to protect people from ionizing radiation should be commensurate with the risks avoided. This article evaluates the recommended protective actions with respect to the optimization principle. The evaluation is based on both recent radiation risk estimates and a derivation of the monetary value of a reduction in risk. It is estimated that evacuation of a population sector should be carried out only if the evacuation will reduce the collective dose equivalent to the population by 1 person-Sv or more for every U.S. +34,000 to +250,000 in net evacuation costs. Therefore, the decision to evacuate should be based on the dose that would be avoided by the evacuation and predetermined site-specific evacuation costs, rather than simply projected dose to the population. Findings further suggest that separate PAGs for the thyroid and skin are unnecessary for protecting against stochastic effects because use of the effective dose equivalent concept eliminates the need for these guides. Separate PAGs for specific organs need only ensure that significant nonstochastic effects are prevented. PMID- 1880022 TI - Catalog of risks extended and updated. AB - A large variety of risks are quantified in terms of the loss of life expectancy they cause in the United States. Risks considered include the following: diseases; accidents of various types at home, at work, in public, and in motor vehicles; unemployment; poor social connections; use of small cars; smoking; air pollution; other environmental pollutants leading to cancer and non-cancer effects; purposely ingested substances; sports participation; geography; medical care; epidemics; natural hazards; socioeconomic factors; Rn and other radiation; and energy conservation. A few suggestions for applications of this catalog of risks are offered. PMID- 1880023 TI - Plutonium- or americium-induced liver tumors and lesions in beagles. AB - Plutonium-239 or 241Am administered intravenously in the monomeric citrate form was initially deposited in beagle livers principally in the hepatocytes and to a much lesser extent in the sinusoidal macrophages and connective tissues. The initial distribution was quite uniform throughout the hepatic parenchyma; however, at later postinjection intervals, depending on the amount of injected activity, the liver burden became increasingly more focal due to: (1) a progressive shift of the radionuclide from the hepatic epithelium to the macrophages; (2) the movement of such macrophages toward the portal or central regions of the lobule; and (3) the displacement of the older more radioactive tissue by regenerating hepatocytes, which generally have a much lower radionuclide content. The hepatic lesions produced by Pu or Am included: (1) necrosis and degenerative changes that were clinically serious or fatal in some of the animals injected with approximately 107 kBq kg-1; (2) marked structural and circulatory changes resulting from necrosis and focal hepatocyte hyperplasia; (3) a significant incidence of both benign and malignant primary liver tumors. In both Pu- and Am-treated dogs, the most frequently appearing neoplasm was the bile duct adenoma, followed by the cholangiocarcinoma. The most obvious difference between Pu- and Am-induced liver neoplasia was the greater frequency of fibrosarcomas and mast cell sarcomas in the Am-treated groups. Hepatomas were of relatively low frequency in animals with Pu or Am burdens. Although the incidence of bone neoplasia was high among the dogs in these studies, the risk of liver tumors, especially in the Am-treated animals, exceeded that of the skeleton in some of the lower dosage levels where the survival times were long. A risk coefficient of approximately 1200 fatal liver malignancies (10(4) beagle Gy)-1, derived from the dosage groups with long survival times, was calculated for combined Pu and Am animals. The prominence of the liver syndromes in beagles with burdens of Pu or Am indicates that humans with body burdens of 239Pu, 241Am, or other actinide elements may be at risk from radiation effects in the liver, including neoplasia development. PMID- 1880024 TI - Fluence rate of radon from soil: effect of sorption barriers, moisture content, and temperature. AB - The effects of activated carbon (AC) and mordenite (termed additives here) on the fluence rate of Rn gas from soil over a range of moisture contents and temperatures were examined in an effort to develop mitigation strategies for Rn in indoor environments. It is possible that an additive--an effective sorbent for Rn--could be mixed with the layer of soil placed adjacent to the substructure of buildings during their construction. The following variables and levels within each variable were examined: additive--0, 25, and 50 wt% mixed with the top 20% of the soil in columns; degree of water saturation, S-5, 30, and 55%; and temperature--5, 13, and 21 degrees C. At any level, mordenite was not effective in decreasing the Rn fluence rate from soil. On the other hand, when AC was present at the 25% level (at S = 30% and temperature = 13 degrees C), the fluence rate was about 5 mBq m-2 s-1 compared to approximately 12 mBq m-2 s-1 for the soil with no additive or one containing mordenite. The fluence rate was even less for levels of AC greater than 25%. AC effectively reduced the Rn fluence rate over all moisture contents and temperatures that were examined. The fluence rate increased with increasing moisture content; this was likely due to an increase in the emanation coefficient for Rn with increasing moisture content. The fluence rate increased or decreased with increasing temperature depending on the amount of AC present in the soil. The results indicate the AC may be an effective additive to soil backfill materials to limit the migration of Rn from the soil into buildings. PMID- 1880025 TI - Monitoring underground radiation fields using powdered calcium sulfate thermoluminescent dosimeters. AB - Powered thermoluminescent dosimeters, CaSO4:Dy, were used to monitor underground radiation fields. Methods of monitoring at selected sites in Taiwan are described; exposure rates above ground at the monitoring sites are also included for comparison. Differences in exposure rates between above ground at 1 m and underground at -2 m may reach 0.516 nC kg-1 h-1. The key factor affecting exposure rates underground is the water content in soil or precipitation that may reduce the diffusion of Rn. The difference in exposure rates between rainy days and sunny days may reach 0.774 nC kg-1 h-1. An example of applying this monitoring technique at a radwaste repository is given. PMID- 1880026 TI - Incorporation of simulated waste raffinates containing 134Cs into cement-clay matrices. AB - Simulated waste solutions containing 134Cs were incorporated into cement matrices at varying compositions and in the presence and absence of various additive materials. Montmorillonite and kaolinite clay minerals, in addition to sand, were added for improving the properties of the cement composites. The leachability of 134Cs was measured for different cement-clay mixtures. The effect of the presence of ions, such as borates, sulphate, and nitrates commonly found in waste raffinates, was also investigated. The results for compressive strength and leachability were explained in light of the effect of the presence of clay additives on cement matrices. PMID- 1880027 TI - Concept of a "lifetime dose" of 350 mSv. AB - After the Chernobyl accident, a number of radiation protection criteria for the early and intermediate phases of the accident were set up by the authorities to protect the public in affected areas. For the late phase, an intervention level of 350 mSv over a lifetime, the so-called 350-mSv concept, has been recommended by the National Council on Radiation Protection and Measurements (NCRP) in the USSR. This concept has been strongly criticized by opponents in the affected republics as being far too high and therefore inhumane. However, a lifetime dose of 350 mSv would impose on an individual an average annual risk of the order of 10(-4) y-1, which is lower than the annual individual risk due to nonradiation causes prevailing in many areas in the USSR. The basic radiation protection principles for nuclear accidents as recommended by the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency (IAEA) are at present very difficult to apply in the USSR because the concepts of risk and acceptable risk are rejected categorically. If, however, principles of justification and optimization had been used, the result might have shown that the present lifetime dose limit of 350 mSv, as an intervention level, is actually too low. PMID- 1880028 TI - Too little concern for breast cancer risk in radiation protection estimates? AB - Risk estimates of radiogenic breast cancer from recent consensus reports are found to depend as much on the models used as on the data. Some features of the models of BEIR V and the ICRP 1990 Recommendations are hardly supported in the literature and tend to underrate breast cancer risk in radioprotection. PMID- 1880029 TI - Year-to-year variations in annual average indoor 222Rn concentrations. AB - Annual average indoor 222Rn concentrations in 40 residences in and around Grand Junction, CO, have been measured repeatedly since 1984 using commercial alpha track monitors (ATM) deployed for successive 12-mo time periods. Data obtained provide a quantitative measure of the year-to-year variations in the annual average Rn concentrations in these structures over this 6-y period. A mean coefficient of variation of 25% was observed for the year-to-year variability of the measurements at 25 sampling stations for which complete data were available. Individual coefficients of variation at the various stations ranged from a low of 7.7% to a high of 51%. The observed mean coefficient of variation includes contributions due to the variability in detector response as well as the true year-to-year variation in the annual average Rn concentrations. Factoring out the contributions from the measured variability in the response of the detectors used, the actual year-to-year variability of the annual average Rn concentrations was approximately 22%. PMID- 1880030 TI - Management of mixed wastes from biomedical research. AB - Mixed radioactive and chemical wastes generated by biomedical research were characterized, and various treatment methods for reducing their volume were evaluated. These wastes consist primarily of organic solvents used in the extraction and purification of radiolabeled biomolecules that are contaminated with low levels of the long-lived radionuclides, 3H and 14C. The Rockefeller University's mixed wastes fall into three broad chemical categories: phenol/chloroform, acetonitrile/water, and mixtures of miscellaneous solvents such as carbon tetrachloride, benzene, and other hazardous chemicals. Currently, with the exception of liquid scintillation cocktails (deregulated in 1981), there are no commercial disposal outlets for mixed wastes nor may they be stored legally for more than 90-180 d. Most of these mixed wastes can be effectively rendered into nonradioactive chemical and aqueous radioactive waste, both of which can be disposed of in accordance with existing regulations. However, to do so requires a Resource Conservation and Recovery Act (RCRA) Part B permit for licensure as a treatment, storage, and disposal facility. For many university research facilities, this may require financial and personnel resources disproportionate to the small amounts of waste produced. Also, such treatment, if not done properly, presents potential occupational hazards from the direct handling of waste materials. Deregulation of certain mixed wastes would be the safest, most cost-effective, and practical method for dealing with many mixed wastes of biomedical origin. In any event, a national regulatory solution must be found. PMID- 1880032 TI - Say it loud. PMID- 1880031 TI - A list of nuclear medicine radionuclides and potential contaminants for operators of in-vivo counters. AB - Operators of in-vivo counters often encounter unusual photopeaks, some of which may be attributed to nuclear medicine radiopharmaceuticals recently received by the subject. This article lists the most common radiopharmaceuticals used in nuclear medicine, their common uses, their half-lives and principal decay energies, and the half-lives and decay energies of any contaminants or daughter products they may contain. The purpose is to help the in-vivo counter operator track down and eliminate causes of such unusual photopeaks. PMID- 1880033 TI - Infant death inquiry launched. PMID- 1880034 TI - Cheap or cheerful? PMID- 1880035 TI - School nurses. Hitting the vulnerable. PMID- 1880036 TI - Primary care. Back in the driving seat. PMID- 1880037 TI - Female circumcision. Should angels fear to tread? AB - Female circumcision has been banned in this country since 1985. But is statutory intervention an appropriate way to tackle an issue so highly charged with complex taboos of race, culture and sexuality? Are we talking about a religious rite--or about child abuse? PMID- 1880038 TI - In pursuit of excellence. AB - Health visitors must look beyond current challenges and pressures and continue to develop innovative practice based on identified client need, argues FRANCES APPLEBY. There is ample evidence that health visitor intervention is effective in improving child and maternal health and that of other client groups. Heath visitors should use this to promote their skills and role in health promotion and prevention of ill health. PMID- 1880039 TI - Are fathers' views important? AB - A survey by health visitors of the behaviour of children between the ages of three and eight revealed that mothers consistently rate children's behaviour as significantly more problematic and more intense than fathers do. Both mothers and fathers viewed the behaviour of boys as more difficult than girls. Pamela Mack, Karen Trew discuss the value of using a behaviour checklist as one aide in the assessment of childhood behaviour problems, with particular emphasis on the importance of involving fathers. PMID- 1880040 TI - The parents' group: a multidisciplinary project. AB - A regular group to support young mothers is an important resource, enabling them to share common concerns, write Wendy Birkinshaw, Pauline Darby and Susan Strasser. A multi-disciplinary approach, with ongoing management supervision, brings a broader perspective and reassurance through difficult periods. PMID- 1880041 TI - A professional visit to Pakistan and Azad Kashmir. AB - Watford health visitor June Mitchell visited north east Pakistan and Azad Kashmir last year. Many health visitors have clients with close ties to Azad Kashmir. She describes three health initiatives she observed there. PMID- 1880042 TI - Men's health. Opening the flood-gates. AB - The health needs of adult men traditionally tend not to come high on health visitors' lists of priorities, if only because of difficulty of access. Few adult men would think to seek the advice of the health visitor. Cath Jackson reports on the last of the 1990 National health visitor week award-winning projects which successfully tracked this elusive client group to its lairs. PMID- 1880043 TI - Selecting a topic. PMID- 1880044 TI - Trusts. Re-negotiating the wheel. PMID- 1880045 TI - Sticking my neck out. PMID- 1880046 TI - Relationship between allozymes, heterozygosity and morphological characters in red deer (Cervus elaphus), and the influence of selective hunting on allele frequency distribution. AB - Morphological characters in red deer (Cervus elaphus), which serve as criteria for selective hunting, were examined in relation to electrophoretic variation in three populations from the Vosges in eastern France. From the polymorphic loci examined, certain alleles at Idh-2, Me-1 and Acp-1 showed significant associations with a special development of body and antler characters selected for by hunters. Idh-2(125) was associated with larger hind foot length in females and a higher number of antler points in males. Me-1(90) and Acp-1(100) were associated with small spikes. The populations studied differed from one another in the duration and intensity of selective hunting and the increase or decrease in the respective allele frequencies could be explained by selection for large body size, a high number of antler points and against small spikes in yearlings, rather than by genetic drift. Among other morphological characters examined, the length of the main beam was significantly associated with the allele Acp-2(100). In contrast, no associations could be detected between overall heterozygosity and the development or the degree of asymmetry (in paired structures) of any of the morphological traits in question. Although no obvious differences in the overall values of polymorphism or heterozygosity were found between the populations, selective hunting leads towards a change in allele frequencies and eventually to the loss of one or the other rare allele. PMID- 1880047 TI - Wrinkling of the eye in hybrids between Drosophila virilis and Drosophila lummei is caused by interaction of maternal and zygotic genes. AB - Hybrids of Drosophila virilis females and Drosophila lummei males have visible developmental anomalies in external adult structures. Reciprocal hybrids are normal, and the anomalies are not found in other interspecific F1 hybrids of the virilis subgroup. Antibiotic treatments with ampicillin, streptomycin and tetracycline did not cure the syndrome. The genetic basis of the wrinkling of the compound eye was analysed in detail. Both male and female F1 progeny of D. virilis mothers were affected, indicating that wrinkling of eyes is maternally determined. F1 hybrid females produced healthy progeny. Backcross hybrid females (D. virilis x F1) with 16 different combinations of autosomes, either heterozygous or homozygous for D. virilis, were crossed with D. lummei males. It was found that homozygous D. virilis chromosomes 2 and 5 together were necessary to induce the maternal effect. The hybrid zygote responded to the maternal effect when the chromosomes 2, 4 and/or 5 were heterozygous. Elimination of the small sixth (dot) chromosome of D. lummei from the hybrids was correlated with the wrinkling of eyes, but was not the cause, as the two phenomena had a different genetic basis and temperature response. Furthermore, the eyes were wrinkled in flies which presumably had had no D. lummei dot chromosome to lose. PMID- 1880048 TI - Multiple paternity in wild common shrews (Sorex araneus) is confirmed by DNA fingerprinting. AB - We have tested for the occurrence of multiple paternity in wild common shrews by karyotypic analysis and DNA-fingerprinting of five wild-caught females and their litters. Karyotypic data suggest that some litters were sired by more than one male, but provide no definitive evidence. By using DNA-fingerprinting, it was possible to establish that two males sired the litter of two females. The present report shows that multiple paternity is not a rare phenomenon in the common shrew and by using DNA-fingerprinting it is possible to assign individual offspring to different male parents even when none of the putative fathers are available for inspection. PMID- 1880049 TI - Microgeographic distribution of allele frequencies in populations of Calomys laucha (Rodentia, Cricetidae). AB - The microgeographic differentiation of allelic frequencies was analysed in two population samples of Calomys laucha, collected in a grid set in cultivated fields at Laguna Larga (Cordoba province, Argentina). One of the samples (n = 79) was obtained in May (Autumn), when the population density is at a maximum, and the other (n = 85) in November (spring), at the onset of reproductive activity. FST values for the November sample show significant differences between the six groups over which the sample was divided. FIT values show an excess of homozygotes for some loci in both samples. FIS reveals an excess of homozygotes within each of the groups. These results indicate the existence of subdivision in the population. Because C. laucha is a reservoir host of the Junin virus, an agent of endemic disease, this social organization may have epidemiological implications. Stratification of C. laucha populations into small breeding units could be one of the factors responsible for the high genic variability detected in this species. PMID- 1880050 TI - Positional control of chiasma distribution in the house mouse. Chiasma distribution in mice homozygous and heterozygous for an inversion in chromosome 1. AB - An examination of the chiasma distribution in chromosome 1 of male mice homozygous and heterozygous for a distal inversion In(1) 12Rk and in normal males was carried out. No differences in chiasma distribution were found between homozygotes for the inversion and homozygotes for normal chromosome 1. A significant decrease in the frequency of bivalents bearing chiasmata in the pretelomeric region was found in heterozygotes. This, in its turn, produced a redistribution of chiasmata in the proximal non-inverted part of bivalent 1. These results could be interpreted as evidence for positional control of the chiasma distribution pattern: the distance of certain parts of the chromosome from the telomere and chiasmata interference are more important for determination of the chiasma frequency in a given region than its genetic content. PMID- 1880051 TI - Antiidiotypic antibodies to HLA class I alloantibodies in normal individuals: a mechanism of tolerance to noninherited maternal HLA antigens. AB - Recent reports indicate that 25%-50% of transplant patients exhibit B-cell nonresponsiveness to their noninherited maternal HLA antigens (NIMAs). To test the hypothesis that tolerance of NIMAs is mediated by antiidiotypic antibodies, sera from seven normal human subjects were tested for the capacity to inhibit the reactivity of HLA alloantisera directed to NIMAs. Five of seven sera inhibited (50%-100%) the cytotoxicity of monospecific alloantisera directed to their NIMAs. This inhibition was specific in that antisera directed to third-party HLA antigens were not inhibited. Cytotoxicity inhibition by normal sera was selective for antisera directed to HLA-B locus antigens. Absorption with an antibody specific for an HLA class I framework determinant eliminated the inhibitory activity of three of the five sera, suggesting that the inhibition was mediated by soluble HLA antigens in these cases. However, two of the sera retained inhibitory activity following soluble antigen depletion, suggesting that, in these cases, inhibition is mediated by antiidiotypic antibodies. This hypothesis was confirmed by purifying the immunoglobulin (Ig) fraction of one of these sera by anti-Ig affinity chromatography; the column eluate (Ig fraction) but not the effluent (Ig-depleted serum) was capable of inhibition. These data are consistent with the hypothesis that tolerance of NIMAs is mediated, at least in part, by antiidiotypic antibodies. PMID- 1880052 TI - Phylogeny of primate major histocompatibility complex DRB alleles. PMID- 1880053 TI - Major histocompatibility complex ancestral haplotypes in the chimpanzee: identification using C4 allotyping. AB - In humans, certain major histocompatibility complex (MHC) supratypes mark unique DNA segments which have been conserved from a common but remote ancestor. In order to determine whether these ancestral haplotypes (AHs) exist in nonhuman primates, C4 allotyping was undertaken on 71 chimpanzees. Four large pedigrees were available. There are at least seven codominant C4 alleles at two loci. Null alleles are also present. It was possible to assign class I, class II, and C4 alleles to 37 unrelated haplotypes; several supratypes occurred two or more times. These putative AHs included some with alleles which resemble those carried by certain human AHs. These data provide evidence that similar MHC AHs are present in the chimpanzee and human. The present approach provides a basis for comparative studies examining the evolutionary and functional significance of the MHC. PMID- 1880054 TI - Academic performance of mature-age and other students in a physiotherapy program. AB - Students enrolled in the physiotherapy undergraduate program of the University of Sydney comprise school leavers (students who have completed secondary school category A) and non-school leavers (category B), including mature-age students (23 years and older). Student selection is based upon academic performance (categories A and B) and personal interview (category B only). Statistical evaluations of the academic performance of 799 students who commenced the undergraduate course between 1982 and 1986 revealed a) no significant difference between the time taken to complete the undergraduate program; b) in 26 of 31 compulsory subjects, category A and category B students performed equally well; in one subject category, B students performed significantly better; in three subjects, the mature-age students performed significantly better; and only in one subject did mature-age students perform less well; c) no difference in the academic performance of male and female students; d) the Higher School Certificate aggregate provided a poor to moderate indicator of academic performance. The results justify both the reservation of places offered to nonschool leavers and the system used for their selection. PMID- 1880055 TI - The need for policy-relevant research and the role of allied health researchers. PMID- 1880056 TI - The 1991 Deans' Memorial Lecture: a perspective on fund-raising with a liberating ideology. PMID- 1880057 TI - Community oriented primary care: an emerging health promotion strategy. PMID- 1880058 TI - Rethinking the promotion and tenure process. PMID- 1880059 TI - The impact of AIDS on recruitment in the health professions. AB - The occupational risk of AIDS has been identified as a possible factor in the decline of applicants to health professions programs. This study examined data obtained from 914 Philadelphia public and parochial high school students concerning their knowledge and attitudes about AIDS, and their knowledge and attitudes toward the health professions. The survey revealed that the majority of respondents demonstrated a good, basic understanding of the transmission of the virus. While fear of exposure to the virus may negatively impact some prospective students, the majority in this study did not express this concern. Rather, the results indicated that the respondents' lack of knowledge and understanding of the health professions is a major reason that they may not be selecting health careers. Notably, more than 50% of those surveyed responded that high schools do not provide enough information about the health professions. These findings reinforce the need for creative recruitment and career counseling programs that will foster an interest in the health professions. PMID- 1880061 TI - Isolation and characterization of new allosamidins. AB - Three of new allosamidins, termed glucoallosamidins A (5), B (6) and methyl-N demethyl-allosamidin (4), were isolated as yeast chitinase inhibitors from the mycelium of Streptomyces sp. SA-684. PMID- 1880060 TI - Antibiotic GE2270 a: a novel inhibitor of bacterial protein synthesis. II. Structure elucidation. AB - GE2270 A, produced by Planobispora rosea ATCC 53773, inhibits Gram-positive bacteria and anaerobes by acting on the bacterial protein synthesis. The structure has been determined by physico-chemical methods applied to the intact molecule and to the main hydrolysis products. Characterization by UV, IR, NMR (double quantum filter COSY), acid-base ionization, elemental analysis and FAB-MS indicated that GE2270 A is a highly modified peptide having MW 1,289 and formula C56H55N15O10S6, and a weak basic function, and that it belongs to the thiazolyl peptide group of antibiotics. Acid hydrolysis yielded a main product (MW 634), responsible for the chromophoric absorption, and a number of hydrolyzed products of lower MW. 13C NMR inverse techniques and MS studies (EI, positive ion chemical ionization, and collision induced dissociation FAB-MS-MS experiments) on GE2270 A, the chromophoric compound, and the other hydrolysis products led to the complete identification of the various amino acid residues and their sequence. Two out of the six chiral centers have been determined. The structure is thought to originate from modification of a chain of 14 amino acids in a process which creates 6 thiazole rings and one pyridine. The modification process also closes the linear polypeptide to form a cyclic part with an attached side-chain. GE2270 A plausibly has a similar biosynthetic origin to that of other thiazolyl peptide antibiotics such as nosiheptide and micrococcin. PMID- 1880062 TI - Herbicidal nucleosides from microbial sources. AB - The structures of five naturally-occurring herbicidal nucleosides have been determined by spectral analysis. Three (5'-deoxyguanosine, coaristeromycin and 5' deoxytoyocamycin) are novel natural products while the remaining two (coformycin and adenine 9-beta-D-arabinofuranoside) are known natural products which have not previously been reported to be herbicidal. PMID- 1880063 TI - Fluvirucins A1, A2, B1, B2, B3, B4 and B5, new antibiotics active against influenza A virus. I. Production, isolation, chemical properties and biological activities. AB - Five unidentified actinomycete strains produced a series of novel antiviral antibiotics which have a unique 2,6-dialkyl-10-ethyl-3(or 9)-hydroxy-13 tridecanelactam nucleus substituted with 3-amino-3,6-dideoxy-L-talose or 3-amino 3,6-dideoxy-L-mannose(L-mycosamine). The antibiotic components exhibited potent inhibitory activity against influenza virus type A Victoria strain infection in Madin Darby canine kidney cells by the cytopathic effect reduction assay. PMID- 1880064 TI - Fluvirucins A1, A2, B1, B2, B3, B4 and B5, new antibiotics active against influenza A virus. II. Structure determination. AB - A series of structurally related antiviral antibiotics, fluvirucins A1, A2, B1, B2, B3, B4 and B5 have been isolated from the fermentation broths of five unidentified actinomycete isolates. Based on spectroscopic analysis, partial degradation experiments and 13C-enriched acetic acid-fed biosynthetic studies, their structures were elucidated to be 2.6,10-trialkyl-3(or 9)-aminoglycosyl-13 tridecanelactams. PMID- 1880065 TI - Fluvirucins A1, A2, B1, B2, B3, B4 and B5, new antibiotics active against influenza A virus. III. The stereochemistry and absolute configuration of fluvirucin A1. AB - Fluvirucin A1 was established as (2R,3S,6R, 10S)-3-[(3-amino-3,6-dideoxy-alpha-L talopyranosyl)-oxy]-2,6-dimethyl-10 -ethyl-13-tridecanelactam by chemical, spectroscopic, and X-ray crystallographic analyses. PMID- 1880066 TI - Pannorin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor produced by Chrysosporium pannorum. AB - Pannorin, a naphthopyrone that inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis, was isolated from a culture broth of Chrysosporium pannorum M10539 by solvent extraction, Bio-Gel P-6 column chromatography and reverse phase HPLC (Silica ODS). Spectroscopic analyses of the compound yielded 4,8,10-trihydroxy-5-methyl 2H-naphtho[1,2-b]pyran-2-one as the proposed structure. Pannorin inhibited HMG CoA reductase and in vitro sterol synthesis 50% at a concentration of 160 microM. PMID- 1880067 TI - Synthesis and nematocidal activities of jietacin A and its analogs. AB - Simple, efficient syntheses of jietacin A, a nematocidal antibiotic, and its analogs have been developed in order to study structure-activity relationships. A series of alpha,beta-unsaturated azoxy compounds was prepared from phenylselenomethyl azoxy compounds as key intermediates and its nematocidal activity was determined. PMID- 1880068 TI - Inactivation of fusidic acid by resistant Streptomyces strains. AB - Streptomyces lividans and several other Streptomyces species are resistant to the steroid-like antibiotic fusidic acid. This resistance is mediated by structural modification of the antibiotic. Using TLC, CD, UV, IR, NMR and mass spectroscopy the structure of one of the resulting inactive compounds was determined. It is derived from fusidic acid by the loss of an acetyl group and the formation of a lactone ring between C-21 and C-16. In addition, helvolic acid, a compound closely related to fusidic acid, has been shown to be modified. PMID- 1880069 TI - Arabenoic acid, a natural product herbicide of fungal origin. PMID- 1880070 TI - Secondary metabolites by chemical screening. 4. Detection, isolation and biological activities of chiral synthons from Streptomyces. PMID- 1880071 TI - Revised structure and the chemical transformations of FR900148. PMID- 1880072 TI - Microbial conversion of milbemycins: 13 beta, 29-dihydroxylation of milbemycins by soil isolate Streptomyces cavourensis. PMID- 1880073 TI - Pure-tone overstimulation protects surviving avian hair cells from acoustic trauma. AB - It was found that intense pure-tones which damage hair cells in chicks, also result in damage to the tectorial membrane (TM). This study was designed to elucidate the effects of a second pure-tone insult on hair cells which survived a priming pure-tone exposure. Chicks were exposed to a pure-tone of 1.5 kHz at 124 dB SPL. Lesion was found in both TM and hair cells, but the area of damage to the TM was much larger than that to the hair cells. Following this exposure, chicks were exposed to a second intense pure-tone at 2.2 kHz 124 dB SPL. The frequency of the second exposure corresponded to a region where the TM did, but hair cells did not appear to be injured by the first exposure. The second exposure caused significantly less hair cell damage in chicks already exposed to the 1.5 kHz pure tone than in controls which were not primed with the first exposure. This finding suggests that the first exposure provides a degree of protection for the surviving hair cells, perhaps by uncoupling them from the TM. PMID- 1880074 TI - Altered susceptibility of 2f1-f2 acoustic-distortion products to the effects of repeated noise exposure in rabbits. AB - Hearing sensitivity and the generation of acoustic-distortion products at 2f1-f2 were examined systematically in behaviorally trained rabbits, before, during, and following regular exposure to a 95-dB SPL octave band of noise, centered at 1 kHz. During the exposure period, the octave-band noise was interrupted once every 24 h in order to monitor the progressive loss in auditory function using tests of behavioral threshold and distortion-product otoacoustic emissions (DPOAEs). When low-frequency DPOAEs from 1-4 kHz diminished to noise-floor levels, i.e., when their amplitudes were reduced by about 20-30 dB, the exposure was terminated. Subsequent recovery of behavioral thresholds and DPOAE amplitudes and detection 'thresholds' was evaluated at regular intervals over a 3-week post-exposure period. Following the recovery period, the rabbits again received the identical exposure/recovery treatment until a permanent 10 dB or greater loss in DPOAE amplitudes was achieved for any point of measurement between 2-10 kHz. The primary result was that the number of days of overstimulation required for rabbits to reach the criterion loss in DPOAE amplitudes increased for each successive exposure session. In addition, DPOAEs accurately tracked the frequency pattern described by the behavioral threshold shifts during both the development and recovery stages of exposure. PMID- 1880075 TI - Same location of the source of P1 of BAEPs and N1 of CAP in guinea pig. AB - The purpose of this study was to point out the location of N1 and N2 of the compound action potential (CAP) and the first waves of the brainstem auditory evoked potentials (BAEPs) by the mean of the section of the eighth nerve at the porus acousticus in guinea pigs. Our results agree with most of the studies in the literature. In the absence of lesion of the internal auditory artery, the section of the cochlear nerve induced the persistence, alone, of the P1 of BAEPs in which latency was similar to initial P1 before section, and the subsequent waves disappeared. Simultaneously, a monophasic negative potential (N1) of the auditory nerve remained without N2. When the section included the internal auditory artery all BAEPs and CAP components disappeared simultaneously and very suddenly just after the section. These results definitively excluded a proximal contribution of the cochlear nerve in the N1 of CAP and P1 of BAEPs. The N2 of CAP and P2 of BAEPs are not generated, even in part, in the intracochlear or intrapetrous portion of the cochlear nerve. PMID- 1880076 TI - Rate/level functions of auditory-nerve fibers in young and quiet-aged gerbils. AB - Steady-state rate/level functions of single auditory-nerve fibers to characteristic frequency (CF) tone bursts were measured in quiet-aged (35-37 months) and young control (4-7 months) gerbils. Rate/level functions of aged gerbils are different from those of young controls in that the thresholds are shifted to higher sound levels, but otherwise the shapes of the aged and young rate/level functions are similar. Specifically, there is little difference in the slope of the dynamic range portion of the rate/level functions when comparing aged gerbils to young controls. This is in contrast to whole-nerve input/output (I/O) functions of aged gerbils, which exhibit slopes that are less steep than those of the young controls (Hellstrom and Schmiedt, 1990b). Thus, it is likely that the deterioration of the CAP I/O function in aged animals is not due to a deterioration of rate/level functions in single units, but rather to other factors such as spiral ganglion cell degeneration or a loss of synchrony. PMID- 1880077 TI - The effects of DFMO on polyamine metabolism in the inner ear. AB - Difluoromethylornithine (DFMO) is a novel antineoplastic agent that was associated with an unexpected hearing loss in Phase II clinical trials. DFMO interferes with polyamine synthesis by inhibition of the enzyme ornithine decarboxylase (ODC). The objective of the current study was to establish a methodology to determine the effect of DFMO on polyamine levels and ODC activity in the cochlea. Guinea pigs received DFMO in their drinking water and were tested for auditory brainstem response threshold shifts. The organ of Corti, the lateral wall, and the acoustic nerve were assayed for both ODC activity and polyamine levels. In DFMO treated animals there was an inhibition of ODC activity in cochlear tissues as well as in intestinal mucosa. In addition, a significant depletion of cochlear polyamines was observed in the treatment animals. This study suggests that systemically administered DFMO inhibits ODC activity and interferes with polyamine synthesis in the cochlea. PMID- 1880078 TI - Effects of myelin or cell body brainstem lesions on 3-channel Lissajous' trajectories of feline auditory brainstem evoked potentials. AB - Auditory brainstem evoked potentials (ABEP) were recorded from 16 awake cats to obtain 3-Channel Lissajous' Trajectories (3CLTs) using three orthogonal differential electrode configurations (nasion-midline nuchal ridge, left-right mastoids, vertex-midline under the mandible). Potentials, evoked by monaural 80 dBnHL (re, human threshold) clicks, were studied before, and up to 7 weeks after inducing neuronal lesions localized to the cochlear nucleus (CN) or the superior olivary complex (SOC), or myelin lesions localized to the fibers of the trapezoid body connecting these two structures. Neuronal lesions were induced by injection of kainic acid (KA), while myelin lesions were induced by injection of L-alpha lysophosphatidylcholine (LPC). With CN neuronal lesions the major changes in 3CLT were in the time domain of 'b', 'c' and 'd' (components P2, P3 and P4 of single channel ABEP). With SOC neuronal lesions the major changes were in 'c' and 'd' of 3CLT (P3 and P4 of ABEP). With trapezoid body lesions the major change was in 'c' (P3 of ABEP). The results are compatible with the peripheral generation of the first ABEP components (P1a and P1b). The second component (P2) is generated by ipsilateral CN neurones and their outputs. The third component (P3) is generated primarily by ipsilateral SOC neurones and their outputs, with the ipsilateral CN providing input. The The fourth component (P4) is generated bilaterally by the SOC neurones and their outputs, receiving their inputs from ipsilateral CN. The fifth ABEP component (P5) is generated by structures central to the SOCs and their immediate outputs. Neither focal neuronal nor myelin lesions were sufficient to produce obliteration of any component, consistent with a set of generators for each of the ABEP components, consisting of both cell bodies and their output fibers, that is distributed spatially in the brainstem. PMID- 1880079 TI - The organ of Corti in the bat Hipposideros bicolor. AB - The bat Hipposideros bicolor (Hipposideridae, Microchiroptera) is the mammalian species with the highest upper limit of hearing in which the structure of the organ of Corti has been studied. H. bicolor emits pure tone echo-locating signals of 153 kHz, compensates for Doppler shifts in the echo and hears ultrasonic frequencies up to 200 kHz (Neuweiler et al., 1984). The organ of Corti was investigated qualitatively and quantitatively using the technique of semi-thin sectioning. Some complementary ultra-thin sections were also examined. Length, width and cross-sectional area of the basilar membrane, the tectorial membrane, the hair cells with their stereocilia and the organ of Corti were measured at equi-distant positions on the basilar membrane. The organ of Corti of H. bicolor is composed of elements similar to those found in the cochleae of other eutherian mammals studied. However, in H. bicolor some of these elements show species specific differences when compared to auditorily unspecialized mammals. The most basal region of the cochlea is characterized by miniaturization and re inforcement of macro- and micro-mechanically important elements. This is interpreted as an adaptation for hearing extremely high frequencies. Specialized structures as well as local maxima of 'normal' elements in the basal and middle cochlear region are associated with evaluation of the echos of emitted pure tones. Besides the basal specializations. Hipposideros also shows specializations in the apical, low frequency, region which can be correlated with passive acoustic orientation. PMID- 1880080 TI - Slow variations of the amplitude and frequency of spontaneous otoacoustic emissions. AB - Systematic, slow variations of the amplitude and frequency of spontaneous otoacoustic emissions in human ears, occurring over the first 20-30 min of recording, are described. Experimental observations suggest that these variations may arise from a centrally mediated, bilateral influence on the mechanics of the ear. PMID- 1880081 TI - Contacts between hair cells in the avian cochlea. AB - In the avian papilla basilaris, contacts between hair cells are a common feature. With few exceptions, they only occur between tall hair cells (THC), and they are more frequent in the apical half of the papilla. In this quantitative study, four types of contacts are defined: Protrusion contacts, touch contacts, fusion contacts and multiple contacts. There are strong indications that these contacts are dynamic structures. The fact that avian hair cells probably communicate with each other means that their function can only be fully understood if cell groups are studied. PMID- 1880082 TI - Cochlear cultures as a model system for studying aminoglycoside induced ototoxicity. AB - Light and electron microscopy have been used to evaluate the effects of treating mouse cochlear cultures with the ototoxic aminoglycoside antibiotic neomycin sulphate at concentrations of 0.2 mM and greater for periods of up to 1 hour. Neomycin rapidly induces the formation of numerous, membrane filled blisters on the apical surfaces of the sensory hair cells. Such morphological damage is restricted to the hair cells, and is not observed on the surfaces of supporting cells within the organ of Corti. Hair cells in apical-coil cultures are less sensitive than those in basal-coil cultures, and, at any given point along the cochlea, outer hair cells appear to be more extensively damaged by neomycin than inner hair cells. These morphological effects of neomycin are considerably more severe when the drug is applied in calcium/magnesium free saline, and can be blocked by elevating the saline concentration of either calcium or magnesium. The effects can also be blocked by lowering the temperature to 4 degrees C, but not by either K+ depolarization or the lectin Concanavalin A. The potential value of this culture system as a model for studying aminoglycoside induced ototoxicity is discussed. PMID- 1880083 TI - A primer on digital imaging--post production for still photography: Part I. PMID- 1880084 TI - Medical illustration in Saudi Arabia. PMID- 1880085 TI - Use of the FAX machine for client interface. PMID- 1880086 TI - The management of AIDS patients in the photographic studio. PMID- 1880087 TI - "1 HR PHOTO-MED"--the development of a rapid color print service for an academic health science center. PMID- 1880088 TI - Preparing color slides from color negatives. PMID- 1880089 TI - Photography of very small biomedical objects. PMID- 1880090 TI - Prediction of airway responsiveness to allergen from skin sensitivity to allergen, airway responsiveness to histamine and serum IgE levels. AB - Immediate allergic reaction of the skin, non allergic airway responsiveness of the bronchi, and serum IgE levels were estimated in 25 atopic non asthmatic subjects and 15 controls. A good correlation was observed between these three parameters i.e. patients with positive skin response to allergen had increased airway responsiveness and significantly increased levels of serum IgE. However, the serum levels of IgE provided a significantly better indication of the likely presence of bronchial allergic reactivity than did the skin reactivity. The results indicate that knowledge of the airway responsiveness to histamine, skin sensitivity to allergen and serum IgE levels can predict the presence of airways responsiveness to an allergen. In all atopic non asthmatic individuals with a significant correlation between these parameters, the relevant allergen could stand identified as having the potential to provoke attacks of clinical asthma. PMID- 1880091 TI - Role of oesophageal electrocardiograms in differentiation of old anteroseptal myocardial infarction from emphysema in cases with poor R wave progression in precordial leads. AB - R wave height, S wave depth and the R/S ratio on electrocardiograms obtained with unipolar oesophageal lead recorded at various levels were studied in 54 cases with emphysema without myocardial infarction and 46 cases with healeeed anteroseptal myocardial infarction. All patients had poor R wave progression in anterior precordial leads. The criterion of R wave height of greater than or equal to 7.5 mm at the ventricular level oesophageal electrocardiogram was most sensitive (85.7%), specific (80%) and accurate (82.4%) for the diagnosis of healed anteroseptal myocardial infarction. PMID- 1880092 TI - Comparative study of amoxycillin and amoxycillin/clavulanic acid in lower respiratory infections. AB - A comparison of oral amoxycillin (500 mg tds) with amoxycillin/clavulanic acid (Augmentin; 750 mg tds) for 7 to 10 days was completed in 76 patients with lower respiratory infection. In another 9 patients, intravenous Augmentin alone was administered (1.2 g 8 hourly) for 3 days followed by oral doses as above for 7 days. In 50 (59%) patients the underlying chronic lung disease was bronchiectasis. Clinical improvement (1 + or more) was seen in 66% with amoxycillin, 60% with oral Augmentin and 56% with IV Augmentin. For radiographic improvement the respective figures were 47, 53 and 44 per cent. Bacteriologically, elimination was seen in 8% with amoxycillin and 45% with Augmentin (P less than 0.01), while partial success was seen in 16 and 24 per cent respectively. While for gram positive organisms, both drugs were similar in efficacy, for gram negative strains the overall success was 27% with amoxycillin and 67% with Augmentin. The main organisms isolated were Str pneumoniae (12), Klebsiella (41), Pseudomonas (21), E coli (9), Haemophilus (7) and Staph aureus (6). For bacteriologic sensitivity and consequent success, Augmentin may be superior in respiratory infections. PMID- 1880093 TI - Progressive systemic sclerosis in south India. AB - Seventy eight patients with progressive systemic sclerosis (PSS) were seen over a period of 14 years. They were analysed after clinical, haematological, biochemical, immunological and radiological investigations for comparison with other Indian and Western studies. Nine of the 78 were cases of childhood PSS. There was a female preponderance (3.9:1) and the peak age of occurrence was the 4th decade (32.1%). Arthralgia (53.8%) and skin thickening (70.5%) were the common presenting symptoms. Raynaud's phenomenon (28.2%) was less common. Involvement of the skin was present in all the patients and skin biopsy was positive in 96% of the cases. Joints were affected in 66.7%; internal organs were involved in 52.6%. Antinuclear antibody was positive in 56.8%. Abnormal echocardiography (37.6%) and barium studies (20.4%) were seen. Restrictive airway pattern by pulmonary function test was present in 55%. Death occurred in 5 patients, of whom 3 died of severe pulmonary hypertension. PMID- 1880094 TI - Idiopathic oedema--a missed entity. AB - Twenty nine patients were diagnosed to have idiopathic oedema; 27 (93.1%) of these were females. Associated psychological symptoms were observed in 86.2% of patients. The most common associated symptoms were related to autonomic dysfunction. Obesity and diuretic abuse were found in 48.3% and 41.4% of patients respectively. The association of bizarre symptoms with idiopathic oedema is a common feature. PMID- 1880095 TI - Lipid profile in enteric fever. AB - Lipid profile is known to alter in patients with severe sepsis, but few studies regarding the status of lipid levels in enteric fever are available. Twenty patients with enteric fever, belonging to different age groups and both sexes, along with an equal number of matched patients with fever due to non-enteric causes, were studied with regard to alterations in lipid profile. We observed a severe and protracted hypertriglyceridaemia, decrease in HDL-cholesterol levels and increase in LDL-cholesterol levels in patients with enteric fever at the peak of fever. The values returned to normal on recovery and convalescence. This study serves to highlight the complexity of lipid variation during Salmonella typhi infection. PMID- 1880096 TI - Ascitic fluid protein and cellular changes during diuretic therapy in cirrhosis of liver. AB - Thirty four patients with peritoneoscopy and/or biopsy proven uncomplicated cirrhosis of liver with ascites were studied for the effect of diuretic therapy on ascitic fluid protein and cell count. Renal function tests, liver function tests, ascitic fluid protein concentration and cell count were estimated prior to diuretic therapy and once every week till the end of therapy. There was no change in mean total serum protein (5.71 +/- 0.58 g/dl to 5.72 +/- 0.63 g/dl). The rise in mean ascitic fluid protein from 1.55 +/- 0.77 g/dl to 1.76 +/- 0.79 g/dl was not significant (P greater than 0.05). Twenty one patients (Group I) showed a rise in ascitic fluid protein concentration while 13 patients (Group II) did not show a rise or showed a fall in protein concentration during diuretic therapy. The rise in ascitic fluid protein concentration in Group I from 1.62 +/- 0.69 g/dl to 2.05 +/- 0.67 g/dl was statistically significant (P less than 0.05). Group I patients had a mean weight loss of 6.21 +/- 3.66 kg as compared to 3.15 +/- 2.00 kg in Group II patients (p less than 0.05). There was no other difference between Group I and Group II patients. Only 5 patients showed a rise in ascitic fluid cell count (more than 50 cell/mm3). It is concluded that diuretic therapy alters ascitic fluid protein concentration in a majority of patients but has no significant effect on cell count. PMID- 1880097 TI - Scintigraphic right-to-left liver lobe ratio and liver-to-spleen ratio in cirrhosis and non cirrhotic liver diseases. AB - Various criteria are used together for the scintigraphic diagnosis of cirrhosis as no single criterion may be reliable. However, low right-to-left hepatic lobe uptake ratio has been reported to be sensitive and specific for alcoholic cirrhosis. A low liver-to-spleen uptake ratio has also been reported in various hepatocellular disorders. We tested these ratios in patients with cirrhosis and non cirrhotic causes of portal hypertension. The right-to-left lobe uptake ratio was significantly lower (1.59 +/- 1.23 vs 2.36 +/- 0.63 in normals; p = 0.037) in only Child's C alcoholic cirrhosis, but the sensitivity of this ratio was low (40%) even in this subgroup of cirrhosis (mean +/- SD 1.72 +/- 1.08) as against 1 of 10 patients with non cirrhotic portal hypertension (3.57 +/- 1.33; p = 0.0005). We conclude that the right-to-left hepatic lobe uptake ratio is not a discriminatory scintigraphic sign in liver disease. A low liver-to-spleen uptake ratio can distinguish cirrhosis from non cirrhotic causes of portal hypertension. PMID- 1880098 TI - High density lipoprotein. AB - High density lipoprotein (HDL) is a discoidal particle comprising phospholipid, cholesteryl esters and several apolipoproteins. It serves in transporting cholesterol from the periphery to the liver by the process of "reverse cholesterol transport". Compatible with this is the finding that the mass of the tissue cholesterol pools is inversely related to plasma HDL concentration. The plasma levels of components of HDL are determined by various physiological and pathological factors. The serum HDL levels are lower with advancing age, male sex, and in genetically predisposed, obese, sedentary persons. The effect of diet on serum HDL levels is not established; mild to moderate alcohol intake is associated with high serum HDL level. The main diseases affecting serum HDL levels are uncontrolled diabetes mellitus, uraemia and hyperthyroidism. Anabolic steroids, sex hormones, oral contraceptives, hypocholesterolaemics and beta blockers have been shown to affect serum HDL level variably. There is increasing epidemiological evidence to show that high levels of HDL are protective against coronary heart disease (CHD). A low serum HDL cholesterol concentration (less than 35 mg/dl) is associated with a significant increase in coronary risk in both men and women. Guidelines published by the National Cholesterol Education Programme do not recommend routine measurement of HDL cholesterol and adaptation of therapeutic modalities aiming to raise the low HDL levels. They recommend hygienic means (i.e. smoking cessation, aerobic exercises and weight loss) to raise the HDL cholesterol levels. PMID- 1880099 TI - Statistics for clinicians. 4. Ordinal data. PMID- 1880100 TI - Congenital complete heart block. PMID- 1880101 TI - Ventricular septal defect with aortic regurgitation complicated by pulmonary valve endocarditis. PMID- 1880102 TI - Small bowel adenocarcinoma mimicking tubercular stricture. Role of enteroscopy in early diagnosis. AB - We report a patient with high jejunal stricture initially thought to be tubercular in origin. There was, however, no response to antitubercular treatment and enteroscopic biopsy revealed it to be an adenocarcinoma. This case illustrates the role of enteroscopy and biopsy in the definitive diagnosis of high small bowel strictures. PMID- 1880103 TI - Schmidt's syndrome. AB - Schmidt's syndrome is a condition where there is auto-immune Addison's disease associated with primary hypothyroidism. We present one such case in view of its rarity in Indian literature. PMID- 1880104 TI - Facial hemiatrophy. Report of two cases. PMID- 1880105 TI - Skeletal manifestations in beta-thalassaemia intermedia. AB - Thalassaemia intermedia with distressing complications is reported from India. An 11 year old boy presented with recurrent fractures since 6 years of age. Investigations revealed that he had multiple healed fractures of long bones, hypersplenism, iron overload and a red blood cell half life (t1/2) of 17 1/2 days. Splenectomy was planned. PMID- 1880106 TI - Correct terminology in leukaemia treatment. PMID- 1880107 TI - Klebsiella pneumonia with lung abscess. PMID- 1880108 TI - Splenic infarctions in mixed infection with kala azar and falciparum malaria. PMID- 1880109 TI - Hepatitis B seromarkers among medical and paramedical personnel. PMID- 1880110 TI - Ayurvedic drugs--no more innocent (cardiotoxic aconite) PMID- 1880111 TI - Inferior vena caval obstruction following burns. PMID- 1880112 TI - Yellow oleander poisoning. PMID- 1880113 TI - Interaction of sickle haemoglobin with malaria. PMID- 1880114 TI - Multi drug resistant typhoid fever: a therapeutic challenge. PMID- 1880115 TI - Proximal muscle weakness following snake bite is not rare. PMID- 1880116 TI - Atenolol induced hypotension. PMID- 1880117 TI - Endoscopic injection treatment of non-variceal bleeding. PMID- 1880118 TI - Tropical myositis an unusual presentation. PMID- 1880119 TI - Tropical myositis: complicated by arrhythmias and pleuritis. PMID- 1880120 TI - Hypokalaemic effect of salbutamol and terbutaline in bronchial asthma. PMID- 1880121 TI - Thermostable phenylalanine dehydrogenase of Thermoactinomyces intermedius: cloning, expression, and sequencing of its gene. AB - The gene encoding the thermostable phenylalanine dehydrogenase [EC 1.4.1.-] of a thermophile, Thermoactinomyces intermedius, was cloned and its complete DNA sequence was determined. The phenylalanine dehydrogenase gene (pdh) consists of 1,098 nucleotides and encodes 366 amino acid residues corresponding to the subunit (Mr 41,000) of the hexameric enzyme. The amino acid sequence deduced from the nucleotide sequence of the pdh gene of T. intermedius was 56.0 and 42.1% homologous to those of the phenylalanine dehydrogenases of Bacillus sphaericus and Sporosarcina ureae, respectively. It shows 47.5% homology to that of the thermostable leucine dehydrogenase from B. stearothermophilus. The pdh gene was highly expressed in E. coli JM109, the amount of phenylalanine dehydrogenase produced amounting up to about 8.3% of that of the total soluble protein. We purified the enzyme to homogeneity from transformant cells in a day, with a 58% recovery. PMID- 1880122 TI - Interaction of melittin and phospholipase A2 with azobenzene-containing phospholipid. AB - Interactions of melittin and/or phospholipase A2 (PLA2) with circular dichroism (CD)-active phospholipid, bis(4'-n-octanoxyazobenzene-4-carboxyl)-L-alpha phosphatidylcholin e (CDPC), were studied. In the presence of melittin at a lipid to-melittin molar ratio (Ri) of 5, multilamellar dispersion, composed of CDPC and dipalmitoylphosphatidylcholine with a molar ratio of 1, underwent morphological change to form small melittin-lipid particles. When PLA2 was added to the melittin-lipid particles at 37 degrees C, the CD band at 222 nm exhibited a remarkable enhancement depending on Ri, indicating the formation of melittin-PLA2 lipid complex. After a 30 min incubation of melittin-PLA2-lipid complex at 45 degrees C in the presence of Ca2+, the CD band at 222 nm was still enhanced and a new positive band at 356 nm was observed. On the other hand, in the absence of Ca2+, the CD enhancement characteristic of melittin-PLA2-lipid complex disappeared after the incubation at 45 degrees C. These results suggest that the melittin-PLA2-lipid complex did not undergo any drastic morphological change upon PLA2-catalyzed hydrolysis of lipid, and that Ca2+ is indispensable in order that the melittin-PLA2-lipid complex remains intact and PLA2 exerts efficient hydrolytic activity in the melittin-PLA2-lipid complex. PMID- 1880123 TI - Multi-functional property of rat liver mitochondrial cytochrome P-450. AB - To solve the problem of whether a common enzyme catalyzes both 5 beta-cholestane 3 alpha,7 alpha,12 alpha-triol 27-hydroxylation and 25-hydroxylation of 1 alpha hydroxyvitamin D3 (a synthetic compound used therapeutically for vitamin D deficient diseases) in rat liver mitochondria, enzymological and kinetic studies were performed. A cytochrome P-450 was purified from female rat liver mitochondria based on these catalytic activities and it was found that the two enzyme activities accompanied each other at all purification steps. The 5 beta cholestane-3 alpha,7 alpha,12 alpha-triol 27-hydroxylation activity of the final preparation had a turnover number of 36 min-1, and the value of the corresponding 1 alpha-hydroxyvitamin D3 25-hydroxylation activity was 1.4 min-1. When the enzyme was partially denatured by heating at different temperatures, both enzyme activities declined in a parallel fashion. Treatment of the enzyme with N bromosuccinimide decreased both enzyme activities in a similar manner. 5 beta Cholestane-3 alpha,7 alpha,12 alpha-triol competitively inhibited 25 hydroxylation of 1 alpha-hydroxy-vitamin D3 and vice versa. From these results it was concluded that 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol 27 hydroxylation and 1 alpha-hydroxyvitamin D3 25-hydroxylation are catalyzed by a common enzyme in rat liver mitochondria. PMID- 1880124 TI - Detection of heat-stable delta 3,delta 2-enoyl-CoA isomerase in rat liver mitochondria and peroxisomes by immunochemical study using specific antibody. AB - The subcellular distribution of delta 3,delta 2-enoyl-CoA isomerase [EC 5.3.3.8] and the inducing effect of clofibrate, a peroxisomal proliferator, on the enzyme activity were examined in rat liver. From the results of spectrophotometric investigation of the fractions, which were prepared by sucrose discontinuous gradient centrifugation from the light mitochondrial fraction, the isomerase activity was found in the fractions enriched in mitochondria and those enriched in peroxisomes of the control and the clofibrate treated rat livers. The anti isomerase antibody reacted with both the mitochondrial isomerase and the peroxisomal isomerase, revealing a single band with an apparent molecular weight of 30,000. However, the isomerase was induced by clofibrate administration mainly in the mitochondrial fraction. These results suggest that delta 3,delta 2-enoyl CoA isomerase is located in the mitochondria and the peroxisomes of the normal rat liver, and that the isomerase in the mitochondria is induced by clofibrate administration. PMID- 1880125 TI - Drastic change in the level of actin mRNA in the course of synchronous division in Tetrahymena. AB - Change in actin mRNA level was investigated in the course of synchronous division in Tetrahymena induced by intermittent heat treatment. The level of actin mRNA decreased from just after the end of the heat treatment (EHT) to 45 min after EHT, and then promptly increased before synchronous division at 75 min after EHT. In contrast, levels of the total RNA and mRNAs of Tetrahymena calmodulin and calcium-binding protein of 25 kDa (TCBP-25) increased gradually from EHT to synchronous division. Drastic change in mRNA level before synchronous division seems to be unique to actin mRNA. From the effects of actinomycin D (50 micrograms/ml) on both synchronous division and actin mRNA level, the increase in actin mRNA level starting from 45 min after EHT is speculated to be prerequisite for the oncoming synchronous division. The results of a nuclear run-off experiment supported the above speculation. PMID- 1880126 TI - Renaturation, purification, and characterization of human truncated macrophage colony-stimulating factor expressed in Escherichia coli. AB - A human truncated macrophage colony-stimulating factor (M-CSF) encoding the amino acid residues from 3 to 153 of the native M-CSF was expressed by using a two cistron expression system in Escherichia coli. The truncated M-CSF found in inclusion bodies was renatured and had CSF activity. Purification, which included a QAE-ZeTa preparative cartridge concentration step followed sequentially by HPLC on TSK-gel Phenyl-5PW and TSK-gel DEAE-5PW columns, gave an overall yield of 63.8%. The purified truncated M-CSF had a specific activity of 4 x 10(7) units/mg of protein. Peptide mapping of a lysylendopeptidase digest by reversed-phase HPLC confirmed the amino acid sequence predicted from the cDNA sequence. SDS-PAGE of the purified truncated M-CSF gave a single band at 17 kDa under reducing conditions and at 32 kDa under non-reducing conditions. Activated Thiol-Sepharose 6B column chromatography and other experiments failed to detect any free cysteine residue in spite of the existence of 7 cysteine residues in the truncated M-CSF subunit. These results indicate that it is a dimeric structure linked by one or more intermolecular disulfide bonds. PMID- 1880127 TI - Examination of aglycone-binding site of human salivary alpha-amylase by means of transglycosylation reactions. AB - The active site of human salivary alpha-amylase is composed of tandem subsites (S3, S2, S1, S1',S2', etc.) geometrically complementary to several glucose residues, and the glycosidic linkage of the substrate is split between S1 and S1'. As a matter of convenience, the subsites to which the non-reducing-end part (glycone) and the reducing-end part (aglycone) of the substrate being hydrolyzed are bound are named the glycone-binding site (S3, S2, S1) and the aglycone binding site (S1', S2'), respectively. The features of the aglycone-binding site of human salivary alpha-amylase were examined by means of transglycosylation reaction using phenyl alpha-maltoside (GG phi: G-G-phi) and its derivatives (GAG phi: G-AG-phi, GCG phi: G-CG-phi, AGG phi: AG-G-phi, and CGG phi: CG-G-phi) in which one of the glucose residues (G) has been converted to 6-amino-6-deoxy glucose (AG) or glucuronic acid (CG) residue as the acceptor. A fluorogenic derivative of maltotetraose, p-nitrophenyl O-6-deoxy-6-[(2-pyridyl)amino]-alpha-D glucopyranosyl-(1----4)-O-alpha-D -glucopyranosyl-(1----4)-O-alpha-D glucopyranosyl-(1----4)-alpha-D- glucopyranosyl-(1----4)-alpha-D-glucopyranoside (FG4P, FG-G-G-G-P), was used as the substrate. HSA catalyzed both hydrolysis of FG4P to FG3 (FG-G-G) and p-nitrophenyl alpha-glucoside (G-P) and transfer of the FG3 residue of FG4P to the acceptors. Transfer to GAG phi occurred more effectively than to GG phi. Transfers to GCG phi and CGG phi were less than to GG phi and very little transfer to AGG phi occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880128 TI - Lysozyme-catalyzed reaction in continuous flow system. AB - The lysozyme-catalyzed reaction of chitooligosaccharide was carried out in a continuous flow system in which the solution of substrate, chitooligosaccharide [(GlcNAc)n], flowed into the lysozyme solution in an ultrafiltration apparatus and the products were filtered off. The filtrate was continuously collected in test tubes with the aid of a fraction collector. The product distribution in each fraction was analyzed by high performance gel filtration. Using (GlcNAc)5 as the substrate, the concentrations of products, (GlcNAc)1----4, increased gradually and came to the steady state when the volume of the outflow amounted to sixfold of the inside volume. Before reaching the steady state, the product distribution was quite different from that observed in the closed reaction system, in which the reaction species are not exchangeable through the boundary of the system. The outflows of (GlcNAc)3-5 were delayed in comparison with those of GlcNAc and (GlcNAc)2. The delay period increased with the decrease in substrate concentration, and was shortened by using the [Asp 101 or Trp 62]-modified lysozyme instead of the native lysozyme. These results suggest that the delay in the (GlcNAc)3-5 outflows is caused by the nonproductive binding of the oligosaccharide to the lysozyme molecule. The profile of the flow reaction yields information not only on the catalytic efficiency but also on the substrate binding efficiency of the lysozyme. PMID- 1880129 TI - Unilateral aminoacylation specificity between bovine mitochondria and eubacteria. AB - The present study shows unilateral aminoacylation specificity between bovine mitochondria and eubacteria (Escherichia coli and Thermus thermophilus) in five amino acid-specific aminoacylation systems. Mitochondrial synthetases were capable of charging eubacterial tRNA as well as mitochondrial tRNA, whereas eubacterial synthetases did not efficiently charge mitochondrial tRNA. Mitochondrial phenylalanyl-, threonyl-, arginyl-, and lysyl-tRNA synthetases were shown to charge and discriminate cognate E. coli tRNA species from noncognate ones strictly, as did the corresponding E. coli synthetases. By contrast, mitochondrial seryl-tRNA synthetase not only charged cognate E. coli serine tRNA species but also extensively misacylated noncognate E. coli tRNA species. These results suggest a certain conservation of tRNA recognition mechanisms between the mitochondrial and E. coli aminoacyl-tRNA synthetases in that anticodon sequences are most likely to be recognized by the former four synthetases, but not sufficiently by the seryl-tRNA synthetase. The unilaterality in aminoacylation may imply that tRNA recognition mechanisms of the mitochondrial synthetases have evolved to be, to some extent, simpler than their eubacterial counterparts in response to simplifications in the species-number and the structural elements of animal mitochondrial tRNAs. PMID- 1880130 TI - A highly sensitive method for quantitative analysis of phospholipid molecular species by high-performance liquid chromatography. AB - A highly sensitive method was developed for quantitative analysis of phospholipid molecular species. Diradylglycerols prepared from phospholipids with phospholipase C were converted to the anthroyl-diradylglycerol derivatives, which could be separated into molecular species and sensitively quantified by reverse phase HPLC using a fluorescence detector. All the molecular species of the derivatives had the same peak area per mole, and the peak areas were proportional to the amounts of the derivatives. Quantification could be carried out at the femtomole level. PMID- 1880131 TI - Numerical method to analyze pH-profile from initial velocity data and semi empirical procedure to identify catalytic residues of enzymes using pK and heat of ionization. AB - A numerical computing method to estimate pK and heat of ionization directly from initial velocity data was developed for systematic analysis of rate parameters. Values of rate and thermodynamic parameters were determined together with standard deviations, without using Arrhenius and van't Hoff plots. Distributions of pK and heat of ionization of small-molecular derivatives of aliphatic carboxylates, imidazoles, thiols, and aliphatic amines as possible models for catalytic residues of enzymes were analyzed from a thermodynamic point of view. Each group was classified in a parallelogram without overlapping, except for a part of the imidazole and thiol groups. It was shown that values of pK and heat of ionization of carboxylates and histidine residues involved in the catalytic activity of enzymes determined from pH-profile experiments can be classified into similar, though somewhat extended, areas to those of the corresponding small molecular derivatives. Identification of catalytic residues using values of pK and heat of ionization is proved to be a reliable method when the procedure is properly used. PMID- 1880132 TI - Polyamine distributions in thermophilic eubacteria belonging to Thermus and Acidothermus. AB - Triamines such as norspermidine, spermidine, and homospermidine and tetraamines such as norspermine, spermine, thermospermine, and aminopropylhomospermidine were found to be distributed ubiquitously in the eight extremely thermophilic (growing at 70 degrees C) Thermus species tested. Three linear pentaamine (caldopentamine, homocaldopentamine, and thermopentamine), two linear hexaamines (caldohexamine and homocaldohexamine), two tertiary branched tetraamines (N4 aminopropylnorspermidine and N4-aminopropyl-spermidine), and quaternary branched pentaamines such as N4-bis(aminopropyl)norspermidine and N4 bis(aminopropyl)spermidine were detected in T. thermophilus HB8, T. filiformis Wai33 A1, T. flavus AT-62, and T. caldophilus GK24. The linear hexaamines and branched polyamines were absent in T. aquaticus YT-1, T. sp. X-1, T. sp. T2, and T. sp. T351, in which linear pentaamines were minor components. Moderately thermophilic Thermus ruber and Thermus sp. K-2 contained putrescine, spermidine, norspermidine, homospermidine, spermine, norspermine, thermospermine, and aminopropylhomospermidine. No pentaamines, hexaamines, or branched polyamines were found in these two moderately thermophilic Thermus species. On the other hand, moderately thermophilic, acidophilic Acidothermus cellulolyticus was devoid of all the polyamines. PMID- 1880133 TI - Quantitative analysis of the hemoglobin oxygenation state of rat brain in vivo by picosecond time-resolved spectrophotometry. AB - Through the use of a picosecond laser pulse of near-infrared light at 1,064 nm, the temporal profile of the transmitted light through the anesthetized rat head has been investigated. The light intensity at a certain time after the input pulse was exponentially attenuated by the hemoglobin concentration with hematocrit values from 1.5 to 50%, although the transmitted pulse broadened markedly due to scattering by the cerebral tissue. The optical pathlength, which is required for quantitation of the absolute absorbance change, was directly determined, by the time of flight measurement of the light pulses, as the product of the velocity of light in tissue and time. The mean concentration of hemoglobin in the brain could be determined quantitatively by the use of this pathlength. The oxygen saturation of venous blood determined by our time of flight measurement was very close to that in the internal jugular vein determined directly with a gas analyzer. Thus, the picosecond laser technique is useful for quantifying the blood oxygenation in tissues. PMID- 1880134 TI - Three-dimensional structure of Cu,Zn-superoxide dismutase from spinach at 2.0 A resolution. AB - The three-dimensional structure of Cu,Zn-superoxide dismutase from spinach leaves has been determined by X-ray crystal structure analysis. The atomic coordinates were refined at 2.0 A resolution using the Hendrickson and Konnert program for stereochemically restrained refinement against structure factors, which allowed the use of non-crystallographic symmetry. The crystallographic residual error for the refined model was 24.9%, with a root mean square deviation of 0.03 A from the ideal bond length and an average atomic temperature factor of 9.6 A. A dimeric molecule of the enzyme is comprised of two identical subunits related by a non crystallographic 2-fold axis. Each subunit of 154 amino acid residues is composed primarily of eight anti-parallel beta-strands that form a flattened cylinder, plus three external loops. The main-chain hydrogen bonds primarily link the beta strands. The overall structure of this enzyme is quite similar to that of the bovine dismutase except for some parts. The single disulfide bridge (Cys57 Cys146) and the salt bridge (Arg79-Asp101) may stabilize the loop regions of the structure. The Cu2+ and Zn2+ ions in the active site lie 6.1 A apart at the bottom of the long channel. The Cu2+ ligands (ND1 of His-46, and NE2 of His-48, 63, and -120) show an uneven tetrahedral distortion from a square plane. The Zn2+ ligands (ND1 of His-63, -71, and -80 and OD1 of Asp-83) show an almost tetrahedral geometry. The imidazole ring of His-63 forms a bridge between the Cu2+ and Zn2+ ions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880135 TI - Reaction of a human head/neck/torso system to shock. AB - The purpose of this study is to predict human response to, and potential damage from, impact loading by using numerical and physical models to monitor the head and thoracic reactions, intervertebral disk pressures, muscle elongations, and some internal organ pressures. The numerical model consists of a three dimensional lumped-parameter system of ten rigid bodies connected by nine intervertebral joints and 28 muscle pairs. The masses represent the head; cervical vertebrae C1-C2, C3-C4, C5-C6, C7-T1 (the first thoracic vertebra); the entire thorax; lumbar vertebrae L1-L2, L3, L4-L5; and the pelvis. The physical model consists of: a water-filled cadaver skull, held in position by attached ligaments; plastic skeletal components involving vertebrae, sternum, ribs and pelvis; silicon rubber intervertebral disks; fabric muscles and ligaments; and water-filled containers replicating the liver, spleen and kidneys. The pelvis of the model is affixed to a plate mounted on a sled that runs on a track. Loading is applied by deceleration from a given velocity that occurs due to the impact of the sled with a fixed aluminum block. Results from the numerical model are compared with corresponding experimental information from the physical structure. Good correlation was obtained in these comparisons up to about 200-250 ms after impact. The results indicate that the head, cervical muscles and disks in the lumbar region are subjected to the greatest force changes and thus are most likely to be injured. PMID- 1880136 TI - The effect of ankle constraint on the torsional laxity of the knee during internal-external rotation of the foot. AB - The in vivo torsional laxity and stiffness of the knee joint are usually determined by rotating the foot and measuring the torque generated at the knee. However, when rotation is applied to the foot, significant three-dimensional forces and moments are produced at the knee. These forces and moments depend upon the external constraint of the ankle complex, and as a result, the observed laxity of the knee also depends on the ankle constraint. Tests are conducted with the foot of a subject in a shoe, with and without the ankle taped, and in a buckled and unbuckled (ski) boot that can effectively constrain ankle rotation. The average laxity of the primary (linear) region of the axial moment vs internal external rotation is 30% greater when the ankle is constrained by the buckled boot than it is in three other cases of lesser ankle constraint. PMID- 1880137 TI - A two-phase finite element model of the diastolic left ventricle. AB - A porous medium finite element model of the passive left ventricle is presented. The model is axisymmetric and allows for finite deformation, including torsion about the axis of symmetry. An anisotropic quasi-linear viscoelastic constitutive relation is implemented in the model. The model accounts for changing fibre orientation across the myocardial wall. During passive filling, the apex rotates in a clockwise direction relative to the base for an observer looking from apex to base. Within an intraventricular pressure range of 0-3 kPa the rotation angle of all nodes remained below 0.1 rad. Diastolic viscoelasticity of myocardial tissue is shown to reduce transmural differences of preload-induced sarcomere stretch and to generate residual stresses in an unloaded ventricular wall, consistent with the observation of opening angles seen when the heart is slit open. It is shown that the ventricular model stiffens following an increase of the intracoronary blood volume. At a given left ventricular volume, left ventricular pressure increases from 1.5 to 2.0 kPa when raising the intracoronary blood volume from 9 to 14 ml (100 g)-1 left ventricle. PMID- 1880138 TI - Non-homogeneous analysis of three-dimensional transmural finite deformation in canine ventricular myocardium. AB - A new method has been developed for analyzing transmural distributions of finite deformation in canine ventricular myocardium without the need to assume that the strain in a finite volume of the wall is homogeneous. The three-dimensional nodal geometric parameters of bilinear-cubic or bilinear-quadratic finite elements are fitted by least squares to the measured coordinates of 12-18 radiopaque markers implanted in the left ventricular free wall. For six dog hearts, root-mean squared errors in the fitted in-plane coordinates ranged from 0.079-0.556 mm in the end-diastolic reference state and 0.142-0.622 mm at end-systole. The corresponding error ranges in the radial coordinate were 0.042-0.264 mm at end diastole and 0.106-0.279 mm at end-systole. Smoothly continuous transmural profiles of wall strain computed as the element deformed during the cardiac cycle from end-diastole to end-systole showed good agreement with the discrete results of conventional homogeneous analysis. Using the kinematics of a thick-walled incompressible cylinder, overall absolute errors due to the non-homogeneity of myocardial deformation were found to be reduced in the new analysis by 30-35% for typical experimental parameters. Overall relative errors were also reduced (from 23 to 20%). Since measurement errors in the reconstructed marker coordinates were spatially smoothed by the fitting procedure, noise in the computed deformations was also substantially attenuated, and transmural gradients of three-dimensional strain components could be obtained with improved accuracy. Hence physiological factors affected by transmural stress and strain distributions, such as myocardial blood flow, ischemia and hypertrophy, may be better understood. PMID- 1880139 TI - Velocity and turbulence measurements past mitral valve prostheses in a model left ventricle. AB - Thrombogenesis and hemolysis have both been linked to the flow dynamics past heart valve prostheses. To learn more about the particular flow dynamics past mitral valve prostheses in the left ventricle under controlled experimental conditions, an in vitro study was performed. The experimental methods included velocity and turbulent shear stress measurements past caged-ball, tilting disc, bileaflet, and polyurethane trileaflet mitral valves in an acrylic rigid model of the left ventricle using laser Doppler anemometry. The results indicate that all four prosthetic heart valves studied create at least mildly disturbed flow fields. The effect of the left ventricular geometry on the flow development is to produce a stabilizing vortex which engulfs the entire left ventricular cavity, depending on the orientation of the valve. The measured turbulent shear stress magnitudes for all four valves did not exceed the reported value for hemolytic damage. However, the measured turbulent shear stresses were near or exceeded the critical shear stress reported in the literature for platelet lysis, a known precursor to thrombus formation. PMID- 1880140 TI - On the anisotropy of the canine diaphragmatic central tendon. AB - We studied the mechanical and anatomical anisotropy of the canine diaphragmatic central tendon (CT). Dumb-bell-shaped strips with effective dimensions of 10 x 2 mm (length x width) were cut from different regions of the canine diaphragmatic CT in two different orientations relative to the direction of neighboring muscle fibers. Specimens sampled with their long axial dimension oriented parallel to the neighboring muscle fibers were named Group-1 and those sampled with an orientation perpendicular to the neighboring muscle fibers were named Group-2. Results from one-dimensional stress-strain and tensile failure strength tests revealed that the CT is a nonlinear, inelastic, and anisotropic material. Group-1 specimens were found to have a higher stiffness, higher failure strength and higher strain energy density at failure than Group-2 specimens. Polarized microscopy showed that multiple sheets of collagen fiber bundles formed an orthogonal network in the tendon. Collagen fiber bundles along Group-1 direction formed parallel trajectory lines connecting the neighboring costal and crural muscles; bundles along Group-2 direction were observed to orient 90 degrees away. At the central apex region of the CT, collagen bundles of Group-1 formed a fan like trajectory pattern. This collagen network architecture was compared favorably to the trajectories of an approximated principal stress field in the CT due to simulated contractile forces from its adjacent costal and crural muscles. These combined results suggest a structure-function relationship for the anatomical and mechanical anisotropy in the canine diaphragmatic CT. PMID- 1880141 TI - An angular velocity profile in cycling derived from mechanical energy analysis. AB - The contributions of this article are twofold. One is procedure for determining the angular velocity profile in seated cycling that maintains the total mechanical energy of both legs constant. A five-bar linkage model (thigh, shank, foot, crank and frame) of seated (fixed hip) cycling served for the derivation of the equations to compute potential and kinetic energies of the leg segments over a complete crank cycle. With experimentally collected pedal angle data as input, these equations were used to compute the total combined mechanical energy (sum of potential and kinetic energies of the segments of both legs) for constant angular velocity pedalling at 90 rpm. Total energy varied indicating the presence of internal work. Motivated by a desire to test the hypothesis that reducing internal work in cycling will reduce energy expenditure, a procedure was developed for determining the angular velocity profile that eliminated any change in total energy. Using data recorded from five subjects, this procedure was used to determine a reference profile for an average equivalent cadence of 90 rpm. The phase of this profile is such that highest and lowest angular velocities occur when the cranks are near vertical and horizontal respectively. The second contribution is the testing of the hypothesis that the reference angular velocity profile serves to effectively reduce internal work for the subjects whose data were used to develop this profile over the range of pedalling rates (80-100 rpm) naturally preferred. In this range, the internal work was decreased a minimum of 48% relative to the internal work associated with constant angular velocity pedalling. The acceptance of this hypothesis has relevance to the protocol for future experiments which explore the effect of reduced internal work on energy expenditure in cycling. PMID- 1880142 TI - The possible role of poroelasticity in the apparent viscoelastic behavior of passive cardiac muscle. AB - This paper investigates the contribution of extracellular fluid flow to the apparent viscoelastic behavior of passive cardiac muscle. The muscle is modeled as an incompressible, isotropic, poroelastic solid saturated by an incompressible viscous fluid. Based on Biot's linear and nonlinear consolidation theories, solutions are presented for general time-dependent uniaxial loading of unconfined cylindrical muscle specimens. The nonlinear analysis includes the effects of large strain, material nonlinearity, and strain-dependent permeability. The computed results show that, for axial stretch ratios greater than 1.1, the changing permeability and the loading rate strongly affect the total stress relaxation and the short-time relaxation rate. Comparisons of theoretical and published experimental results show that extracellular fluid flow can account for several observed biomechanical features of passive myocardium, including the insensitivity of stress-strain curves to loading rate and of stress-relaxation curves to the amount of stretch. Theoretical hysteresis loops, however, are too small. Thus, both poroelastic and tissue viscoelastic effects must be considered in studies of passive cardiac muscle. PMID- 1880143 TI - Axial forces and normal distributed loads in twining stems of morning glory. AB - In analysing the mechanics of twining, we hypothesize that contact forces are important in maintaining the twining habit of viny stems. This hypothesis is formalized with a description of the force balance in the natural coordinate system associated with the Frenet vectors attached to the 'generative helix' of the vine. The force balance indicates that, if shear forces are neglected, an axial force within the stem is balanced by a normal load distributed along the line of contact between the supporting pole and the stem. Two kinds of empirical studies were conducted to verify the importance of the putative normal load. Firstly, vine geometry was measured on and off the supporting pole. When removed from the pole, the helical stem forms a coil of smaller radius, smaller wavelength and larger torsion. Next, forces were estimated from observations of the pressure exerted by a stem twining around a water-filled balloon. Twining around a dowel 0.95 cm in diameter, a typical stem of morning glory (Pharbitis nil) sustains a tension of 100 g balanced by a normal distributed load of -30 g cm-1. Thus the twining stem puts itself into tension and uses a helical geometry to generate contact forces which are large relative to the stem weight of 40 mg cm-1. PMID- 1880144 TI - A model of the alar ligaments of the upper cervical spine in axial rotation. AB - Although there are seven vertebrae in the human cervical spine, over 50% of the total axial rotation occurs between the first and second vertebrae, at the atlanto-axial joint. Such motion is possible because of the lack of an intervertebral disc and the shape of the articular facets. The limitation of axial rotation, essential because the spinal cord and vertebral arteries cross this joint, is achieved with ligamentous structures, of which the left and right alar ligaments are primary. When one of the alar ligaments was cut in previous tests of human cadaveric spine (n = 10), the axial rotation to both sides significantly increased. This result does not agree with the long-held hypothesis that axial rotation is limited only by the alar on the side opposite rotation. The purpose of this work was to develop a model of the alar ligaments in axial rotation that is consistent with recent experimental observations. This model predicts that both alars must be intact to limit axial rotation; if one alar is injured, the normal mechanism becomes nonfunctional. The model also predicts the observation that a significant percentage of rotation at the atlanto-axial joint occurs freely, without ligamentous resistance. A physical and a mathematical description of the model is presented. Cadaveric experimental data are demonstrated to support the model. PMID- 1880145 TI - Inertia and muscle contraction parameters for musculoskeletal modelling of the shoulder mechanism. AB - To develop a musculoskeletal model of the shoulder mechanism, both shoulders of seven cadavers were measured to obtain a complete set of parameters. Using antropometric measurements, the mass and rotational inertia of segments were estimated, followed by three-dimensional measurements of all morphological structures relevant for modelling, i.e. muscle origins and insertions, muscle bundle directions, ligament attachments and articular surfaces; all in relation to selected bony landmarks. Subsequently, muscle contraction parameters as muscle mass and physiological cross-sectional area were measured. The method of data collection and the results for inertia and muscle contraction parameters as prerequisities for modelling are described. PMID- 1880146 TI - The effect of test methodology on apparent compressive stiffness of tibiofemoral joint specimens. AB - Several investigators have analysed the compressive load bearing properties of the knee. Careful review of these force/displacement data showed considerable variation, with some investigators reporting displacements 12-15 x higher than others for nearly identical testing conditions using the same animal model. In this study, we sought to determine if this variability was inherent in the tibiofemoral joint or if differences in experimental methodology explained the variation. Compressive force/displacement curves were obtained from 39 normal canine tibiofemoral specimens mounted in a universal testing machine. Two commonly reported methods of measuring compressive displacement were used simultaneously. The testing machine crosshead displacement was used as one measure of displacement of the joint. The other method consisted of extensometers mounted to bone at the joint line. Resultant joint rotation in the parasagittal plane was also measured. Using either approach, we found comparatively little variation among the 39 specimens tested. However, the crosshead displacement measurements diverged from the extensometer measurements as the compressive load increased. At 770 N, the crosshead measurement was nearly twice the extensometer displacement. Further analysis showed that the compliances differed by a uniform amount. Parasagittal joint rotation, as measured by the extensometers, was minimal--less than one half of one degree. Although our loading fixtures were expected to be rigid under the loads used, these data suggest that the deformation of the bone and loading fixtures was responsible for the differences we observed, and may be responsible for the variation in compressive displacement results among several published studies. A model is presented which uses a simple elastic element to represent this deformation. PMID- 1880147 TI - Correction formulae for the misalignment of axes in the measurement of the orthotropic elastic constants. AB - In the experimental determination of the orthotropic elastic constants, one often encounters the situation in which the symmetry axes of the material are not coincident with specimen axes along which the material testing is accomplished. The problem of calculating the compliance coefficients in the symmetry coordinate system from measurements of the compliance coefficients made in an arbitrary, specimen fixed, coordinate system is considered here. PMID- 1880148 TI - Calculation of the instantaneous centre of rotation for a rigid body. AB - The mathematical procedure presented is used for the calculation of the instantaneous centre of rotation for a rigid body based on kinematic measurement data. For every rotation angle interval observed an average centre of rotation is calculated by an appropriate optimizing calculation similar to data approximation by moving average. Practical applicability of this procedure has been proved by means of two planar and one three-dimensional test measurements of known movements (pure rotation, rolling motion and motion of a ball-and-socket joint. PMID- 1880149 TI - A device for the application of known simulated orthodontic forces to human cells in vitro. AB - Connective tissues are responsive to mechanical forces. In orthodontic tooth movement it appears that the periodontal ligament (PDL) is the source of a pleuropotential cell population and extracellular matrix structure which translates mechanical perturbation information into a host of cellular events. These include proliferation, repair, differentiation, and shape change. We have designed, built, and tested a simple, adaptable machine which enables us to examine molecular changes or events in the cell nucleus, cell membrane, and the cytoskeleton of any eukasytic cell that will adhere to a membrane. These responses to clinically simulated forces applied to an in vitro system can be measured. PMID- 1880150 TI - Three forms of rat basic fibroblast growth factor are made from a single mRNA and localize to the nucleus. AB - The molecular weight of rat basic fibroblast growth factor is predicted to be 18 kDa when the amino acid sequence is read from the single AUG initiation codon found in the cDNA. DNA sequencing upstream of this AUG codon indicated, however, that there was an extended open reading frame. In vitro translation of the rat cDNA for basic FGF gave three proteins of 18.0, 21.5, and 22.0 kDa in equal abundance. The same proteins were produced in vivo by COS cells transfected with the rat cDNA. Deletion of 81 base pairs from the reading frame upstream of the AUG codon resulted in the expression of only one protein observed at 18.0 kDa. These results indicated that the 22.0 and 21.5 kDa forms of rat basic FGF were formed when translation initiates at the alternative upstream non-AUG codons. Rat cell lines and tissues were found to express all three forms of basic FGF protein. The cDNA was used to analyze the subcellular distribution of the different forms of rat basic FGF. Subcellular fractionation and immunofluorescence of transfected COS cells showed that all three forms of the protein localized preferentially in the nucleus. Expression of a truncated cDNA from which 81 base pairs (27 amino acids) of the upstream reading frame had been deleted, showed localization of the smaller form of bFGF alone in the nucleus. These results demonstrated that although the amino acids that were deleted from the N-terminus of rat basic fibroblast growth factor have a sequence characteristic of nuclear localization motifs, they are not obligatory for the transport of the growth factor into the nucleus. Nuclear extracts taken from transfected cells also contained two smaller proteins of 16 and 12 kDa that were detected by Western blot analysis. It is possible that these are proteolytic products of bFGF. PMID- 1880151 TI - Growth modulation by epidermal growth factor (EGF) in human colonic carcinoma cells: constitutive expression of the human EGF gene. AB - The functional role of epidermal growth factor (EGF) in epithelium-derived human colonic carcinoma cells was investigated by transfection with plasmid pUCDS3, which contained synthetic human EGF encoding sequences, into two human colonic carcinoma cell types with dissimilar phenotypic properties: the moderately differentiated and growth factor-responsive Moser and the highly metastatic KM12SM cells. The Moser cells exhibited a proliferative response to treatment with exogenous EGF, while the KM12SM cells did not. The constitutive expression of the human EGF gene in these colonic carcinoma cell types resulted in elevated expression of EGF mRNA, with concurrent production and secretion of a large amount of EGF, and downmodulation of transforming growth factor-alpha (TGF-alpha) secretion. Growth stimulation and down-modulation of both high and low affinity EGF receptors were observed in the EGF-transfected Moser clones. Results of experiments using anti-EGF and anti-EGF-receptor antibody to block the proliferation of EGF-transfected Moser clones suggested that autocrine stimulatory mechanisms involving both EGF and TGF-alpha were operative in these cells. By comparison, a growth-inhibitory effect, with no apparent EGF receptor modulation, was observed in the EGF-transfected KM12SM clones. Both the parental and EGF-transfected KM12SM clones possessed fewer EGF receptors than the Moser cells, and anti-EGF or anti-EGF-receptor antibody did not affect the cells' growth properties. These results suggested that the mechanisms of growth inhibition in the EGF-transfected KM12SM clones were non-autocrine or intracellular in nature. Thus, constitutive expression of the human EGF gene in two phenotypically different, epithelium-derived human colonic carcinoma cells resulted in divergent altered growth characteristics. PMID- 1880152 TI - Differential regulation of the expression of transforming growth factor-beta s 1 and 2 by retinoic acid, epidermal growth factor, and dexamethasone in NRK-49F and A549 cells. AB - Although most biological activities of transforming growth factor-beta s 1 and 2 (TGF-beta 1 and TGF-beta 2) examined in vitro are similar or identical, recent studies suggest that each of these factors may be independently regulated in vivo. In this study we have used highly sensitive and specific sandwich enzyme linked immunosorbent assays for TGF-beta 1 and TGF-beta 2 to examine the effects of a variety of treatments on expression of these two TGF-beta isoforms. We show that epidermal growth factor (EGF) induces secretion of TGF-beta 1 and not TGF beta 2, whereas retinoic acid (RA) induces secretion of TGF-beta 2 and not TGF beta 1 in NRK-49F normal rat kidney fibroblasts and A549 human lung carcinoma cells. Moreover, treatment with EGF diminishes the levels of TGF-beta 2, while RA decreases the levels of TGF-beta 1 in both cell lines. Dexamethasone (Dex), on the other hand, inhibits the secretion of both TGF-beta 1 and TGF-beta 2 in A549 cells, while selectively inhibiting TGF-beta 1 secretion in NRK-49F cells. The interactive effects of EGF, RA, and Dex on the production of TGF-beta 1 and TGF beta 2, which were studied on NRK-49F cells, demonstrate that EGF blocks the induction of TGF-beta 2 mRNA and peptide by RA, while Dex inhibits the induction of TGF-beta 1 mRNA and peptide by EGF. These results demonstrate that RA, EGF and Dex are each unique, differential, and interactive regulators of the expression of TGF-beta s 1 and 2. PMID- 1880153 TI - Heat shock induces two distinct S6 protein kinase activities in quiescent mammalian fibroblasts. AB - The regulation of S6 kinase activity was used to monitor perturbations of intracellular signaling activity during heat shock of quiescent murine and human fibroblasts. Previous reports on exponentially growing insect and plant cells had indicated that 40S ribosomal protein S6 is dephosphorylated during heat shock; thus inhibition of S6 kinase activity by heat shock was anticipated in NIH 3T3 fibroblasts and human cells (HeLa, diploid embryonic fibroblasts MRC-5, and skin derived fibroblasts). Unexpectedly, two distinct S6 protein kinases were activated in quiescent fibroblasts after heat exposure. One of the enzymes was partially purified by sequential column chromatography and was determined to be equivalent to the enzyme activated by serum and other growth factors, referred to here as pp70-S6 protein kinase. The other protein S6 kinase, pp90rsk, was identified by a specific immunoprecipitation assay. Monitoring both enzymatic activities during heat shock revealed a temporal pattern of activation that was reversed when compared to non-stressed, mitogen-stimulated cells. Finally, heat shock stimulated protein S6 phosphorylation in cultured, quiescent mammalian cells. These data demonstrate that specific protein kinases can be activated during heat shock, and that some early mitogenic signals may also participate in the response of cells to physiologic stress. PMID- 1880154 TI - Apoptosis of murine BW 5147 thymoma cells induced by dexamethasone and gamma irradiation. AB - The mode and the kinetics of the death of T-thymoma cells upon dexamethasone treatment and gamma-irradiation (10Gy) have been studied using flow cytometry and biochemical analysis. It has been shown that the hormone and gamma-irradiation induce cell death by apoptosis. In both cases the cells are initially blocked in G2/M and die only after overcoming the blockage and cytokinesis. A short exposure to dexamethasone results in a cytostatic effect, whereas a cytotoxic effect is absent. Reducing serum concentration to 2% causes more rapid death both following gamma-irradiation and dexamethasone. These results are discussed in relation to cell death and proliferation. PMID- 1880155 TI - Heparanase activity in cultured endothelial cells. AB - This study was undertaken to identify a heparan sulfate (HS) degradation endoglycosidase (heparanase) in cultured endothelial cells (EC) and to characterize the requirements for its release and subsequent degradation of HS side chains in the subendothelial extracellular matrix (ECM). Intact EC, EC lysates, or EC conditioned media from different sources were incubated with metabolically Na2(35)SO4-labeled ECM produced by bovine EC. The released sulfated products were analyzed by gel filtration on Sepharose 6B. Human umbilical vein endothelial cells (HUVEC) and human saphenous vein endothelial cells (HSVEC) lysates expressed heparanase activity as indicated by release of most of the radioactivity from ECM as HS fragments that are one-fifth to one-sixth the size of the intact HS side chains. These fragments were sensitive to deamination with nitrous acid and were not produced in the presence of heparin. Rabbit coronary microvascular EC and bovine brain capillary EC lysates showed less heparanase activity (30-35%), whereas bovine aortic and corneal EC showed no activity. Intact HUVEC, plated directly on the labeled ECM, expressed low enzyme activity that was not changed when cells were exposed to various agents. Exposure of HUVEC to interleukin-1, phorbol myristate acetate, tumor necrosis factor, endotoxin, thrombin, calcium ionophore A23187, fibroblast growth factor, or radiation did not induce release of the enzyme to the medium or degradation of HS in the ECM, as long as the cells remained viable. EC differ from various normal and malignant cells that degrade HS by virtue of their inability to release the enzyme. We suggest that heparanase release during vessel wall injury may regulate the growth of EC and smooth muscle by release of HS degradation products in processes such as wound healing, neovascularization, and atherosclerosis. PMID- 1880156 TI - Effect of trifluoperazine on renal epithelioid Madin-Darby canine kidney cells. AB - Following exposure to a number of hormones, the cell membrane in Madin-Darby Canine Kidney (MDCK) cells is hyperpolarized by increase of intracellular calcium activity. The present study has been performed to elucidate the possible role of calmodulin in the regulation of intracellular calcium activity and cell membrane potential. To this end trifluoperazine has been added during continuous recording of cell membrane potential or intracellular calcium. Trifluoperazine leads to a transient increase of intracellular calcium as well as a sustained hyperpolarization of the cell membrane by activation of calcium sensitive K+ channels. Half-maximal effects are observed between 1 and 10 mumol/L trifluoperazine. A further calmodulin antagonist, chlorpromazine, (50 mumol/L), similarly hyperpolarizes the cell membrane. The effects of trifluoperazine are virtually abolished in the absence of extracellular calcium. Pretreatment of the cells with either pertussis toxin or phorbol-ester TPA does not interfere with the hyperpolarizing effect of trifluoperazine. In conclusion, calmodulin is apparently involved in the regulation of calcium transfer across the cell membrane but not in the stimulation of K+ channels by intracellular calcium. PMID- 1880157 TI - Enhanced inhibition of tissue factor by the extended form of an endothelial cell glycoprotein (an extrinsic pathway inhibitor). AB - We have identified, in the supernatant medium of cultured endothelial cells, an additional inhibitor of tissue factor that is eluted at higher salt concentrations during heparin-Sepharose chromatography and is a much more potent inhibitor of the activation of the coagulation cascade than the species we studied earlier (Colburn and Buonassisi: In Vitro Cellular and Developmental Biology 24: 1133-1136, 1988). The inhibitor we described earlier has been shown to be functionally and immunologically identical to a rabbit plasma extrinsic pathway inhibitor, EPI (Warn-Cramer et al.: Thrombosis Research 61:515-527, 1991). The new species (molecular mass, 47 kDa) is susceptible to proteolytic cleavage which results in a sharp reduction of its ability to inhibit tissue factor and an increase in electrophoretic mobility compatible with a molecular mass of 45 kDa, the same as that of the inhibitor reported earlier. Based on these data, we suggest that the new inhibitor yields, through proteolytic cleavage of an amino acid sequence of about 25 residues, the N-glycan-sulfated compound previously described. PMID- 1880158 TI - Problems of the distal radioulnar joint. PMID- 1880159 TI - Classification of distal radioulnar joint disorders. AB - The wrist is one of the most complex articulations in the human body. The distal radioulnar joint (DRUJ) is particularly controversial, enduring as the area least understood with regard to anatomy and pathomechanics. The popular systems of classifying DRUJ disorders are based on etiology and treatment, but this approach has inspired schemes that are cumbersome, redundant, and incomplete. The need for an improved system prompted us to devise a simplified system that is based on the pathomechanics of dysfunction and the mechanical requirements for optimal joint function. PMID- 1880160 TI - Histologic anatomy of the triangular fibrocartilage. AB - Histologic examination of the TFC reveals parallel, longitudinally oriented collagen fibers peripherally, while the more central articular disc is made up of interweaving obliquely oriented sheets of collagen fibers. This suggests a peripheral region experiencing tensile loads between the region of origin from the radius and the area of insertion into the ulna. The fiber orientation in the central region is more compatible with a structure experiencing multidirectional stresses. The articular disc origin from the radius is reinforced by collagen bundles projecting out from the radius for 1 to 2 mm. A large number of traumatic tears are oriented parallel to the radial origin of the TFC and located approximately 1 to 2 mm from the origin site. This corresponds to the junction of the short, radially oriented fibers and the remainder of the articular disc. The inner 80% of the articular disc is avascular, as is its radial attachment. Traumatic tears in this region would have a low healing potential unless some method for introducing additional vascularity was undertaken, such as reattachment through drill holes in the radius, allowing neovascularization of this otherwise avascular region. PMID- 1880161 TI - Imaging of the distal radioulnar joint. AB - The distal radioulnar joint can be evaluated by many different imaging techniques, including plain radiography, arthrography, tomography, nuclear medicine bone scanning, computed tomography, and magnetic resonance imaging. Each of these techniques has advantages and disadvantages that must be considered when determining the appropriate diagnostic evaluation for a particular patient. PMID- 1880162 TI - Arthroscopic treatment of TFCC lesions. AB - The TFCC bears axially applied load and stabilizes the distal radioulnar joint. Palmer's classification of TFCC lesions into traumatic and degenerative injuries allows a rational approach to treatment. Wrist arthroscopy provides both diagnostic and therapeutic capabilities in the treatment of these lesions. PMID- 1880163 TI - Acute injuries of the distal radioulnar joint. AB - Acute injuries of the distal radioulnar joint are common. They often are not treated aggressively owing to a failure to diagnose or the misconception that there is little functional impairment if left untreated. Early aggressive treatment with restoration of anatomic alignment and stability will yield optimum results. Acute treatment usually produces a better functional outcome than late reconstructive procedures. PMID- 1880164 TI - The ulnar impaction syndrome. AB - The ulnar impaction syndrome can be defined as the impaction of the ulnar head against the triangular fibrocartilage complex and ulnar carpus resulting in progressive degeneration of those structures. The differential diagnosis in patients who present with ulnar wrist pain and limitation of motion can also include ulnar impingement syndrome and arthrosis or incongruity of the distal radioulnar joint. Structural abnormalities involving the distal radioulnar joint, distal radius, and ulnar carpus must be carefully elucidated prior to developing a treatment plan. When such abnormalities are identified and appropriately addressed, surgical treatment can be expected to be effective in the majority of cases. It is important to remember that in the absence of obvious structural abnormalities, the ulnar impaction syndrome may result from daily activities that result in excessive intermittent loading of the ulnar carpus. In this group of patients, treatment is directed at decreasing ulnar load by shortening the distal ulna in any of several ways. If relative instability of the ulnar ligamentous complex is a factor, then ulnar shortening by recession is the treatment of choice. Malunion of the distal radius resulting in ulnar impaction syndrome is best treated by addressing the deformity; that is, corrective radial osteotomy. Patients who present with a combination of ulnar impaction syndrome along with distal radioulnar joint, abnormalities must have both of these abnormalities addressed at the time of surgery. The matched ulnar resection and the hemiresection interposition arthroplasty are both effective procedures; however, the Suave-Kapandji procedure also can be used to address relative ligamentous laxity at the ulnar aspect of the wrist. The Darrach procedure is presently not recommended as a first-line treatment in these cases; however, when used as a salvage procedure, satisfactory results can be obtained in properly selected patients. Careful preoperative evaluation and planning are therefore the key to successful treatment of the ulnar impaction syndrome. PMID- 1880165 TI - Instability of the distal radioulnar articulation. AB - This complex issue is addressed by a discussion of a classification of clinically observed instabilities. Experimental data and clinical observations are combined to provide a theoretical rationale for understanding the subject. Clinical usefulness is described. PMID- 1880166 TI - The treatment of chronic traumatic subluxation of the distal ulna by hemiresection interposition arthroplasty. AB - Dorsal and palmar subluxation of the distal ulna can be difficult to both diagnose and treat. Patients often present long after their initial injuries with posttraumatic arthritic changes in the distal radioulnar joint. Hemiresection interposition arthroplasty is a salvage procedure that is reliable for both pain relief and restoration of motion. PMID- 1880167 TI - Distal ulna resection, extensor carpi ulnaris tenodesis, and dorsal synovectomy for the rheumatoid wrist. AB - We conclude from this study that distal ulna resection coupled with stabilization by ECU tenodesis is a highly useful technique with a reproducibly successful outcome for DRUJ destruction resulting from rheumatoid arthritis. In this series, like those noted previously, alleviation of pain, preservation of wrist mobility, prevention of tendon rupture, and improved function have been consistently observed. Moreover, with adjunctive dorsal synovectomy this combined procedure has proved applicable to cases demonstrating not only mild but also moderate stages of radiocarpal disease, thereby avoiding the more extensive and less desirable surgical alternatives of complete wrist arthrodesis or total wrist arthroplasty. Recognizably, the long-term benefit of this surgery depends on maintaining stability of both the reconstructed radioulnar joint and the synovectomized radiocarpal joint. Although the data reported herein strongly support the efficacy of the tenodesis in preserving distal ulna stability and similarly indicate a favorable influence on maintenance of radiocarpal architecture, one must be cognizant that progressive radiocarpal deterioration is a characteristic, albeit somewhat unpredictable, manifestation of the chronic rheumatoid process, and is the principal factor apt to compromise an initially satisfactory result. In such cases demonstrating excessive carpal malalignment preoperatively and for those with an unremitting postoperative course of ulnar translocation or volar subluxation, additional radiocarpal stabilization, preferably by arthrodesis, is essential to salvage the benefits of distal ulna resection and ECU tenodesis. PMID- 1880168 TI - Stabilization of the distal ulna. AB - Stabilization of the remaining distal ulna following its resection for various disorders resulting in pain and instability of this joint is necessary for long term satisfactory results. The method described uses a distally based flap of the extensor carpi ulnaris to provide stability of the distal ulna and support to the carpus along its ulnar border. PMID- 1880169 TI - Tenodesis of the chronically unstable distal ulna. AB - Treatment of the chronically unstable distal ulna often requires reconstruction using tenodesis techniques. A review of described techniques for distal ulnar stabilization is presented, addressing chronic instability with and without distal radioulnar joint degenerative disease. PMID- 1880170 TI - The distal radioulnar joint complex in rheumatoid arthritis: an overview. AB - Rheumatoid arthritis frequently involves the distal radioulnar joint region and is progressive. Early recognition of involvement is paramount to offering patients appropriate and timely treatment. Early operative intervention should be considered preventative. Synovectomy, hemiresection interposition technique, matched distal ulna resection and distal radioulnar fusion with creation of a pseudarthrosis through the distal ulnar shaft have been advocated for patients with early involvement. Distal ulnar resection remains the most commonly used procedure for advanced disease. No soft tissue reconstructive procedure to stabilize the ulnar stump offers distinct advantages. They should be considered modifiers and augmentations to distal ulna resection. Judicious resection of the ulnar head minimizes instability of the ulnar stump. The use of an ulnar cap is not recommended for routine use. PMID- 1880171 TI - Excision of the distal ulna in rheumatoid arthritis. AB - Resection of the ulna is an effective operation in the treatment of rheumatoid disorders of the distal radioulnar joint. Tenosynovectomies of the overlying extensor tendons and synovectomy of the joint are integral parts of the procedure. Following resection, the ulna usually remains in alignment with the radius, although some dorsal displacement is common. Restoring stability to the ulna as well as reconstructing a new sheath for the extensor carpi ulnaris can be accomplished in most cases by using the extensor retinaculum. In those cases where the retinaculum has been destroyed by the disease process or when the distal ulna is severely displaced, stability can be restored using the extensor carpi ulnaris for a tenodesis. PMID- 1880172 TI - Radioulnar joint fusion for distal radioulnar joint instability. AB - Each one of this small group of patients illustrates a rare indication for the radioulnar joint fusion procedure in distal radioulnar joint instability. The case histories tell of a last ditch effort to salvage function in an extremity crippled by painful radioulnar instability after excision of the distal ulna. The fusions healed slowly and two required repeat surgery to achieve union. Today we would routinely add iliac bone graft to the fusion area to hasten healing. Rarely indicated, this is a salvage procedure that is done after failure of other procedures geared to preserve the rotation of the forearm. These patients all had successful salvage of their extremities for activities of daily living, but only one returned to his labor job. All were worker's compensation cases in physical jobs. Two patients had had prior radiocarpal fusions, making them even more restricted in function. This procedure should be kept in mind to be used in the rare cases of painful instability of the distal radioulnar joint when traditional motion-preserving procedures have failed. PMID- 1880173 TI - The Sauve-Kapandji procedure for the treatment of posttraumatic distal radioulnar joint problems. AB - The appropriate management of distal radioulnar joint (DRUJ) problems has no consensus. Although the Sauve-Kapandji procedure is not new, little has been written on the indications for its use. Our experience shows that this operation is an effective treatment for patients with some combination of posttraumatic DRUJ problems that involve arthritis, instability of the distal ulna, and ulna plus variance. PMID- 1880174 TI - [Complicated solitary biliary cysts]. AB - With development of ultra sound, solitary hepatic cyst (SHC) appears as a common and benign affection. Complications can occur in 10 per cent of cases. We report here four cases of complicated SHC: vena caval obstruction, intracystic bleeding, rupture, intracystic infection. Those four patients were successfully treated by partial excision of the cyst in the first 3 cases, and by percutaneous drainage with CT scan guidance in the latter. Complications of SHC occur only in large cysts, with a diameter up to 8 cm. So, small SHC do not require any treatment, while large SHC must be treated to avoid complications. Percutaneous aspiration and direct injection of alcohol can lead to recurrence. Surgical therapy by partial excision is successful, with low rates of mortality and morbidity. PMID- 1880175 TI - [Massive hemobilia. Review of the literature. Apropos of 2 cases]. AB - Two cases of hemobilia are reported; the first caused by a liver biopsy procedure, and the second ensuing an accidental liver laceration. In both cases, arteriography led to diagnosis and the ligature of the right hepatic artery stopped the hemorrhage with complete success. A review of the literature emphasizes the nowadays leading prevalence of iatrogenic hemobilia followed by those resulting from blunt abdominal liver trauma. Diagnostic facilities are reviewed and selective arteriography is stressed as being the more useful technique. From a therapeutical standpoint interventional radiology and surgery are both given their own place. PMID- 1880176 TI - [Spontaneous rupture of the liver with hemoperitoneum during pregnancy. Apropos of a case, review of the literature]. AB - We report the case of a patient who, at 28-week amenorrhea, presented with spontaneous hemoperitoneum in a pre-eclamptic syndrome. When caesarean section was performed, abdominal exploration revealed a liver hematoma which caused the rupture of Glisson's capsule. The related literature is reviewed. PMID- 1880177 TI - [A difficult therapeutic dilemma: pneumoperitoneum in severe blunt injuries treated by respiratory or cardiorespiratory resuscitation]. AB - In the particular context of severe blunt trauma treated with cardiorespiratory resuscitation or, more simply, with positive-pressure ventilation, the occurrence of pneumoperitoneum always raises difficult problems of etiological diagnosis, which in turn lead to a difficult dilemma on the treatment to adopt. In fact, while the air released by the alveolar baro-trauma can, once a given pressure is exceeded, migrate into the retroperitoneum and produce a non-surgical pneumascos (for which the other possible causes are far more exceptional, and rather are unpleasant surprises, such as this orogenital induced PPT in Gantt's female patient, conversely the pressurized air from true ruptures of intraabdominal hollow organs may migrate into the mediastinum and cause a thoracic air leakage syndrome that perfectly simulates this pulmonary baro-trauma. Therefore all the paraclinical means required must be used to confirm--or rule out--this diagnosis of perforation, which demands emergency surgery. However, if there is any doubt, the consensus is that emergency surgery is recommended as it is better to accept blank laparotomy than to oversee a gastrointestinal rupture with all its severe complications of evolution. PMID- 1880178 TI - [Primary Salmonella brandenburg peritonitis in a non-immunosuppressed female patient]. AB - Primary peritonitis is rare; the bacteria involved are mainly, by order of frequency: Escherichia coli, Streptococcus pneumoniae, and the other streptococci. Extraintestinal sites of minor salmonellosis are exceptional, although they are constantly progressing, especially since the spread of the HIV induced epidemic. We report one case of primary Salmonella brandenburg peritonitis, whose mechanism could not be explained, in a non-immunodepressive female patient. PMID- 1880179 TI - [Gas gangrene. Clinical considerations, prognosis and therapeutic prospects in our experience]. AB - The prognosis of gas gangrene is changing as the means of treatment become more accurate and are implemented earlier. The authors, in their work referring to 10 cases of gas gangrene, point out to the extreme fastness of debridement and immediate exeresis, of wide-spectrum antibiotic protection and of caloric balance, associated to a treatment using trace elements. The importance of hyperbaric oxygen therapy seems to be increasingly proven with time. Lastly, in their general experience of treatment, the authors suggest the use of a specific frequency soft laser therapy, which might speed up the process of tissue repair. PMID- 1880180 TI - [Compressive thigh hematoma. Apropos of a case of fissured superficial femoral aneurysm in megadolicho-arteries. Review of the literature]. AB - An original case of fissured superficial femoral aneurysm in a context of arteriomegaly is reported. The analysis of the literature emphasizes the great latency of the disease, and the very low frequency of rupture, especially in this site. The key test for follow-up of the disease is Doppler ultrasound. PMID- 1880181 TI - [Pseudotumor form of hepatic tuberculosis. Apropos of a case]. AB - The authors report about one new case of hepatic tuberculosis in a pseudotumoral form, and emphasize the diagnostic difficulties even in a country where tuberculosis is endemic. Hepatic puncture, either with sonographic monitoring or during laparotomy, is the paraclinical examination of choice. The histological study supports the diagnosis. The medical treatment is that of any form of tuberculosis. The surgical treatment is most often indicated when a diagnosis of liver tumor is assumed. PMID- 1880182 TI - [Time of disappearance of artificial pneumoperitoneum in children. Diagnostic value]. AB - Postoperative pneumascos has always been interesting and provocative for surgeons because its "correct" disappearance time still remains ill-defined. Fifty-six children, for whom Golstein's intraoperative diagnostic pneumascos was carried out to demonstrate a contralateral hernia during the correction of a unilateral inguinal hernia, were followed up for disappearance of their pneumascos with abdominal radiographs taken at the 4th postoperative hour and on the 1st, 2nd, 4th and 8th days. The children were divided up into three groups: 9 children were younger than 6 months, 20 were 6 to 24 months old, and 27 were older than age 2. The intraperitoneal free air present in all subjects 4 hours after surgery has completely disappeared from the radiographs of the children younger than 6 months on the fourth day, and on the eighth day for the children aged 6 to 24 months, while a trace of subphrenic air still persisted in the 7% (2 out of 27) of children who were older than age 2. This work is aimed at establishing a correlation between the child's age and the time of disappearance of the pneumascos. PMID- 1880183 TI - [Splenic abscess. Apropos of 5 cases]. AB - Spleen abscesses are infrequent, and are encountered in 0.4 to 0.7%-of the autopsy series. They are diagnosed late and their prognosis is poor. The authors report about 5 cases of spleen abscesses observed at Dakar's University Surgical Clinic over a period of 30 years. The patients were young adults, including one case of sickle-cell anemia. In spite of numerous clinical signs in all cases, the abscess was diagnosed late. In three patients, ultrasound allowed establishing the diagnosis and initiating percutaneous treatment, with no success in two cases. The procedure had consisted in total splenectomy in all cases. One patient died 2 months after surgery, after the evacuation of a hematoma in the splenic compartment. The other 4 patients, seen 7, 4, 3 months and 15 years after total splenectomy, no longer presented with any symptom. The authors emphasize the rarity of spleen abscesses; the fact that the diagnosis is often established late, in spite of the progress made in non-invasive medical imaging, including CT and ultrasound; the physiopathology, etiology and treatment of the disease, the latter still being surgical. PMID- 1880185 TI - [Metachronous nodular leiomyosarcomatosis of peripheral vascular muscle cell in the systemic and regional circulation. A new nosological pattern?]. AB - A patient with five different episodes of single or multiple leiomyosarcomatous nodules in 19 years is described. The nodules were subcutaneous, in the upper lobe of the right lung after 15 years, subcutaneous again after five years and one year later, in the left femoral diaphysis and in the 3rd and 5th abdominal vertebrae two years later. According to the authors, the five different lesions were primary because they were strictly limited to a single organ, they were identical from a histological point of view, no regional glands were affected, and there was no disseminated neoplasia. Finally, the authors emphasize the origin from peripheral vascular muscle cells because of the constant occurrence of peripheral vascular nodules and of signs of vascular muscle cell dysplasia near the neoplastic nodules. They believe to be faced with a new clinical picture which may be defined as: metachronous nodular leiomyosarcoma of peripheral vascular muscle cells in the systemic and lesser circulation. PMID- 1880184 TI - [For a conservative treatment of hydatid cyst of the spleen]. AB - A retrospective study of 45 cases of spleen hydatic cyst. Operated on between January 1980, and December 1989 permitted the following commentary. Splenic hydatic cyst is characterized by its rarity and latency. It's diagnosis gives no rise to any problems. Echography data are essential in asymptomatic froms associated to other localisations. Surgical treatment can not be summarised to splenectomy; conservative methods are used as long as possible. PMID- 1880186 TI - [Papillary carcinoma on cyst of the thyroglossal tract. Apropos of 2 cases]. PMID- 1880187 TI - Electrochemical detection of oligopeptides through the precolumn formation of biuret complexes. AB - The relatively slow kinetics of formation of the electroactive Cu(II)-peptide complexes from larger (greater than 6 amino acids) peptides requires relatively high temperature and long reaction times for a postcolumn reactor. The precolumn incubation of bradykinin, Tyr8-bradykinin and insulin A chain with biuret reagent for 20 min at 60 degrees C leads to the formation of biuret complexes which can be subjected to chromatography in acidic or basic eluents. These complexes are detected electrochemically with a sensitivity similar to the Cu(II)-(ala)3 complex (1 nC/pmol at 1.0 ml/min). The influence of the column-packing material on the electrochemical detector response of the Cu-peptide complexes has also been studied. PMID- 1880188 TI - Separation of carbohydrate-mediated microheterogeneity of recombinant human erythropoietin by free solution capillary electrophoresis. Effects of pH, buffer type and organic additives. AB - Free solution capillary electrophoresis has been investigated as an alternative to isoelectric focusing for the separation of the glycoforms of recombinant human erythropoietin (r-HuEPO), a primary regulator of erythropoiesis. A systematic approach was used to study the effect of pH, buffer type and organic modifiers on the resolution of the microheterogeneity of erythropoietin. The main factors for improving the resolution were the regulation of the electroosmotic flow of the running buffer and the reduction of solute-wall interaction. The best resolution of the glycoforms of r-HuEPO was obtained with a mixed buffer pH 4.0 (100 mM acetate-phosphate, 10 h preequilibration time). PMID- 1880189 TI - Rapid isolation of a neurohormone from mosquito heads by high-performance liquid chromatography. AB - Methods were developed for the isolation of the egg development neurosecretory hormone, EDNH, from heads of the mosquito Aedes aegypti. This hormone stimulates ecdysone production by ovaries. Methods used for the successful isolation of insulin-like peptides from vertebrate tissues were modified to develop a four step procedure involving extraction in acidified ethanol, precipitation by neutralization, followed by sequential separation on size-exclusion, ion-exchange and reversed-phase high-performance liquid chromatography columns. PMID- 1880190 TI - Gas chromatographic determination of aldicarb and its metabolites in urine. AB - A method is described for the determination of aldicarb and its metabolites (the sulphoxide and sulphone) in urine by gas chromatography with flame photometric detection (GC-FPD). The sample was concentrated with a column containing activated charcoal and Florisil, and then eluted with dichloromethane-acetone (1:1, v/v). The aldicarb and aldicarb sulphoxide in the eluate solution were oxidized to aldicarb sulphone and the total sulphone concentration was determined by GC-FPD after extraction with dichloromethane and clean-up with an activated charcoal column. The detection limit was 0.0024 mg/l. The mean recoveries from spiked urine in the range 0.04-0.12 mg/l were 90.9%, 86.6%, 92.6% for aldicarb, aldicarb sulphoxide and aldicarb sulphone, respectively. PMID- 1880191 TI - Chiral high-performance liquid chromatography of aromatic cyclic dipeptides using cyclodextrin stationary phases. AB - A series of enantiomers of cyclic and linear dipeptides containing aromatic amino acids was prepared and chromatographed on beta- and gamma-cyclodextrin (CD) columns. The retention times, separation factor alpha and resolution values were calculated. The relevance of the distance of the chiral center from the phenyl ring for chiral resolution was studied. A model was developed using X-ray crystallographic data for an inclusion complex of beta-CD and the enantiomers of cyclic (Phe-Gly). PMID- 1880192 TI - High-performance affinity chromatography of a chick lectin on an adsorbent based on hydrophilic polymer gel. AB - A mouse monoclonal antibody (SIA4-5) which reacts with a chick 14K lectin (C14K) was covalently attached to a new support for high-performance affinity chromatography, TSKgel Tresyl-5PW, which is a preactivated, polymer-based particle. The immobilized antibody (SIA4-5-5PW) thus prepared proved to be useful in measuring not only the molecular properties of C14K but also specific interactions of C14K with SIA4-5 and hapten sugars. The C14K preparation was fractionated according to the oligomeric structure and with slight differences in affinity to SIA4-5 although the former was homogeneous in sodium dodecyl sulphate polyacrylamide gel electrophoresis. Application of the method for quantitative analytical purposes was successful. PMID- 1880193 TI - Chromatographic and physical studies of tropomyosin in aqueous-organic media at low pH. AB - Non-cross-linked and disulfide-cross-linked two-chain molecules comprising the alpha and/or beta chains of rabbit skeletal tropomyosin were studied by electrophoretic, chromatographic and physical methods. Elution order on C4 reversed-phase high-performance liquid chromatography depends markedly on the number and position of the cross-links. In the C4 reversed-phase elution medium, cross-linked and non-cross-linked species are greater than 85% helical by circular dichroism, but the non-cross-linked elute later from high-performance size-exclusion chromatography (G4000) and have molecular mass of 31,000-41,000 dalton by equilibrium ultracentrifugation. The data suggest that in the C4 reversed-phase high-performance liquid chromatography elution medium non-cross linked tropomyosin exists as amphipathic single-chain alpha-helices. PMID- 1880195 TI - Assay for both ascorbic and dehydroascorbic acid in dairy foods by high performance liquid chromatography using precolumn derivatization with methoxy- and ethoxy-1,2-phenylenediamine. AB - A procedure for the simultaneous determination of both ascorbic and dehydroascorbic acid in dairy foods by high-performance liquid chromatography using precolumn derivatization with 4-methoxy- and 4-ethoxy-1,2-phenylenediamine is presented. The derivatives are isolated by solid-phase extraction and analysed by fluorescence detection on a resin-type reversed-phase column at pH 9. Retention times are 2 and 3.2 min for the derivatives of ascorbic and dehydroascorbic acid, respectively. Relative standard deviations of the within- and between-assay tests are 7.1 and 5.5%, respectively, for ascorbic and 11 and 9%, respectively, dehydroascorbic acid. The limits of detection are 50 and 70 fmol per 5-microl injection for ascorbic and dehydroascorbic acid, respectively. PMID- 1880194 TI - Chiral copper-chelate complexes alter selectivities in metal affinity protein partitioning. AB - Proteins can be distinguished by exploiting complementarity between a histidine's microenvironment and a metal-chelate ligand in metal-affinity separations. The partitioning behavior of three myoglobins was investigated in aqueous two-phase polyethylene glycol-dextran systems containing polyethylene glycol derivatized with Cu(II) complexes of the L- and D-isomers of methionine and aspartate. TSK chromatographic supports derivatized with the methionine complexes were used to study retention of these proteins in metal-affinity chromatography. In the partitioning studies, the amino acid metal chelates exhibit selectivities for the myoglobins that are different from that of Cu(II)-iminodiacetate. Significant differences in selectivity based on the chiral nature of the amino acid complexes were also observed. The chromatographic selectivities of the chelating ligands exhibit little variation, however, suggesting that interactions occurring in solution but not on a surface play an important role in protein binding to the Cu(II)-amino acid-PEG complexes. In solution, the Cu(II)-amino acid complexes are sensitive probes of the microenvironments of surface histidines. The choice of the metal chelate affinity ligand offers a powerful means by which the selectivity of metal-affinity separations can be altered. PMID- 1880196 TI - Separation and microanalysis of growth factors by Phast system gel electrophoresis and by DNA synthesis in cell culture. AB - A simple, micro-scale method was established for the characterization of growth factors at picogram levels using Phast system gel electrophoresis followed by monitoring the mitogenic activity by DNA synthesis in cell culture instead of staining methods. The separations and bioassays were carried out with a procedure involving Phast polyacrylamide gel electrophoresis or isoelectric focusing, gel slicing along the template, elution of growth factors through Transwell membranes and measurement of [3H]thymidine incorporation into DNA of normal rat kidney (NRK) fibroblasts. Transwell cell culture chamber inserts separated sliced gel pieces from culture cells and also permitted the direct elution of growth factors into the culture medium. The lower limit of sensitivity for human epidermal growth factor (hEGF) and transforming growth factor type alpha (TGF-alpha) were about 50 and 200 pg, respectively. At these concentrations, they were not detectable by the current most sensitive silver staining technique. Iodinated hEGF and TGF-alpha were also used to demonstrate the feasibility of determining the isoelectric point and molecular weight of peptides at picogram levels. This method is reliable, reproducible and can improve current methods for the characterization of growth factors. PMID- 1880197 TI - [Present state of coronary revascularization in ischemic heart disease]. PMID- 1880198 TI - [Purification and characterization of cytosol aminopeptidase from rat intestinal mucosa]. AB - The isolation of cytosol aminopeptidase (CAP) from intestinal mucosa has involved difficult procedures because of low yield, instability of the enzyme and many other factors related to purification. The authors resolved these difficulties in the purification of the enzyme from intestinal mucosa of rats using hydrophobic chromatography on phenyl-TOYOPEARL 650S and ion exchange HPLC on Mono Q 5/5. In this procedure, a 60-fold purification was achieved and the purified enzyme revealed a single band with 56kDa molecular weight by SDS polyacrylamide gel electrophoresis. The purified enzyme preferentially hydrolyzed the Leucyl containing peptides of Leu-Gly and Leu-Gly-Gly. However, it showed no activity on synthetic substrates of Leu-beta-naphthylamide, Gly-p-nitroanilide, Phe-p nitroanilide or Met-beta-naphthylamide. The Km and Vmax for Leu-Gly were 0.91 mmol/l and 16.4 mol/min/mg protein, while for Leu-Gly-Gly they were 0.77 mmol/l and 20.6 mol/min/mg protein. The purified enzyme was heat-labile and quickly became less active in highly concentrated ammonium sulfate. The optimum pH was 6.5-10. The enzyme activity was stimulated by Mn2+ and Mg2+, while it was inhibited by EDTA, 1,10-phenanthroline, 2-mercaptoethanol and p hydroxymercuribenzoate. The results suggested the participation of metal ions and the SH group in the enzyme activity. Furthermore the cytosol aminopeptidase was distinct from the brush-border membrane aminopeptidase in molecular weight, immunoreaction to cytosol aminopeptidase antiserum and the specificities to the substrates. PMID- 1880199 TI - [Relationship between iron nutrition and nutriment intakes in the menstruating and menopausal women]. AB - Medical examinations related to iron nutrition (hemoglobin concentration, serum ferritin concentration and transferrin saturation) and measurements of daily nutriment intakes based on three day dietary records were carried out for 440 female subjects from adolescence to menopause, and the relationships between both parameters were compared. The subjects could be reasonably divided into 3 age groups of menstruating I (17-29 years), II (30-53 years) women and menopausal (48 69 years) women by the one-way analysis of variance. The occurrence of iron deficiency including iron deficient anemia was above 45% both in menstruating I and menstruating II women. In addition, the average amounts of iron intake were 8.7 and 10.2 mg/day in these groups, respectively. These values were below the recommended intake of iron (12 mg/day) for females of these ages in Japan. In menopausal women, the occurrence of iron deficiency decreased to 11.3%, which corresponded to the increase of average iron intake to 11.2 mg/day. Irrespective of age groups, there were almost no significant correlations between the results of medical examinations and the amounts of daily iron intake. Although no improvement in hemoglobin concentration and transferrin saturation was observed in 62 menstruating women, who received 10 mg iron daily as sodium ferrous citrate for 2 months, the average serum ferritin concentrations were significantly increased at 1 and 2 months after the supplement and 2 weeks after they stopped. These therapeutic trials indicate the relationship between iron deficiency and low iron intake in menstruating women. PMID- 1880200 TI - [Long-lasting changes in motoneuron discharges following 50 Hz tetanization of afferent nerves in cats]. AB - The effects of 50 Hz tetanization on motoneuron discharges were studied in non immobilized, non-anesthetized, decerebrate cats. Motoneuron discharges were monitored by recording either muscle (hamstring muscles or foot extensors) action potentials or ventral root (L7 or S1) discharges. In the latter case both ventral and dorsal roots were cut and corresponding dorsal roots were stimulated. It was found that in 13 out of 32 cases the tetanization of the sciatic nerve at 4.0T for 5 s produced enhancement of monosynaptically evoked muscle action potentials (H-wave) for 20-25 min. Three categories of potentials were distinguished in ventral root discharge according to latencies and thresholds: monosynaptic, polysynaptic and late potentials. When the dorsal root was tetanized at 2.5-5.0T for 5 s, all of these 3 categories of potentials exhibited an enhancement of the potential lasting for more than 30 min. The late potential, which was the longest latency polysynaptic potential (4.7-6.5 ms), was the most sensitive to the tetanization. Its enhancement could develop slowly, yet the degree of the enhancement was the greatest, as compared with other two categories of potentials. In contrast, the enhancement of these potentials were always immediate. In 15 out of 46 cases at least one of the 3 categories of potentials exhibited the enhancement. Since the long-lasting changes were induced only with the strength enough to activate polysynaptic pathways, interneurons were considered to be responsible for these plastic changes. The monosynaptic potential could show a long-lasting depression following the tetanization. PMID- 1880201 TI - [Campylobacter enterocolitis complaining of melena]. AB - A 38-year-old man was admitted to our hospital complaining of 5 episodes of melena without abdominal pain or diarrhea. No abnormalities were noted through an upper gastrointestinal endoscopy, but a proctoscopy revealed a large amount of coagulated blood within the rectum immediately before his admission. A colonoscopy revealed spotty redness with dark-red coagulation in the region from the splenic flexure down to the rectum except oral colon beyond the transverse colon. A presumptive diagnosis of campylobacter enterocolitis was made by a microscopy performed on the stool specimen, then an oral administration of erythromycin was started. A colonoscopy done on the 5th hospital day proved improvement on the mucosal changes. The final diagnosis of campylobacter enterocolitis was made by the stool culture. The patient took a satisfactory course of hospitalization and was discharged on the 10th day. Bacteriological examination of stool specimen together with endoscopy has been confirmed to be useful for the diagnosis of melena cases without manifestation of infectious enterocolitis. PMID- 1880202 TI - [New approach to mechanism of atherosclerosis. Scavenger receptor]. PMID- 1880203 TI - Field work of rubella attenuated live virus vaccine in Thailand. PMID- 1880204 TI - A comparative investigation on autologous mandibular and iliac crest bone grafts. An experimental study in sheep. AB - Nine Friesian sheep (age 1.5-2 years) were used to evaluate the quality of bone repair in artificial cleft-like maxillary defects repaired with autologous bone grafts of embryologically different origin. After bilateral extraction of the upper first deciduous molar the tooth socket was enlarged resulting in an open connection between the oral and nasal cavities. In the same session a graft, obtained from the iliac crest, was implanted in one of the two bilateral maxillary defects and on the opposite side a graft, obtained from the mandible, was inserted. During the experiment, serial radiographs were taken. After six months the sheep were sacrificed and the bone of the grafted areas was submitted to histological and histomorphometric investigation. Comparing both areas, it appeared that the quality of bone remodelling and alveolar reconstruction was independent of the origin of the grafts. PMID- 1880205 TI - Incidence of cleft lip, alveolus and palate forms. AB - The different cleft forms of 1,450 cleft lip, alveolus and/or palate patients have been analyzed. Randomized groups of 50 plus the next 50 patients and so forth have been examined. The resulting 29 groups reveal a maximum of 139 different clinical cleft forms. The prediction of a possible maximum was made with the exponential formula y = a. (1-eb.x). The tendency of the prognosis levels at a maximum of 169 different cleft forms in and above 4900 patients. PMID- 1880206 TI - Slot osteosynthesis technique (SLOT) for sagittal ramus split osteotomies. A method to optimize occlusal control and condylar seating. AB - In the technique presented, a specially designed drill and bone holding forceps are used. These enable a horizontal slit to be cut in the condyle-bearing segment, at the site of the largest contact surface. One lag-screw is tightened in the centre of the slit at each side. By releasing the IMF (intermaxillary fixation) and untightening one or both screws, the condylar segments can be repositioned and the occlusion corrected before inserting the other tandem screws. PMID- 1880207 TI - A modified sagittal step osteotomy of the mandibular body. Technical note. AB - A modification of the osteotomy of the body of the mandible for elongation and rotation of its anterior part is presented. It allows these movements without the necessity for bone grafting, with a reduced risk of damage to the alveolar nerve and increased stability. PMID- 1880208 TI - Pterygoid plate separation using an oscillating saw in Le Fort I osteotomy. Technical note. AB - An oscillating saw is used to achieve pterygomaxillary separation. The procedure is quick and simple to perform and avoids the potentially hazardous use of osteotomes for this purpose. Down fracture of the maxilla allows visual confirmation of the integrity of the pterygoid plates. PMID- 1880209 TI - Benign mesenchymoma of the tongue. Report of a case, with review of the literature. AB - A benign mesenchymoma of the dorsal midtongue in an 88-year-old woman is presented. The tumour was excised under local anaesthesia, and microscopic examination revealed cartilage, bone, striated muscle, peripheral nerve, adipose and myxoid tissue, and blood vessels in addition to fibrous tissue. Eight cases including ours were found in the literature. PMID- 1880210 TI - Atypical multiple benign osteoblastomas accompanied by simple bone cysts. A case report. AB - A case of atypical benign osteoblastomas occurring at multiple sites in the maxilla and mandible of a 38-year-old woman, in association with simple bone cysts, is described. The tumors produced hazy or ground-glass-like semiradiolucent lesions with well-defined or poorly-defined margins on conventional radiographs. Histologically, the lesions were characterized by a proliferation of plump osteoblast-like cells forming trabeculae of osteoid and immature bone in a well-vascularized stroma. In addition, simple bone cysts associated with a radiolucent-radiopaque lesion consisting of lamellar bone and loose connective tissue were found next to one of the tumours. Possible pathogenesis of the tumours and cysts is discussed. PMID- 1880211 TI - Bilateral coronoid hyperplasia. Report of two cases and review of the literature. AB - Two cases of bilateral hyperplasia of the coronoid processes of the mandible are presented. The patients were men and first noticed their symptoms at 14 and 10 years of age, respectively. They were treated successfully by intraoral bilateral coronoidectomies. A review of the literature revealed only forty-nine cases of the condition reported; 43 cases in western countries and 6 in Japan. As described previously, the majority of the cases were men and their symptoms occurred under the age of 19 years. PMID- 1880212 TI - Head and neck trauma in sporting activities. Review of 208 cases. AB - Head and neck injuries due to sports and games represent 22.7% of all injuries admitted to the E.N.T. Department of the University of Perugia between 1980 and 1988. Epidemiological and causative factors of these injuries are examined by the authors, together with their treatment: the majority of accidents occurred during soccer games as a consequence of collisions between players. In these cases the most frequently recorded lesion was a nasal fracture. Other sporting activities were responsible for more serious injuries to the maxillo-facial bony, cartilaginous and soft tissue structures. Good results were achieved both on the anatomical and functional planes, except for a few cases of facial disruption and multiple mandibular fractures. The authors stress the importance of preventive measures, consisting of periodical medical check-ups, an adequate level of umpiring and the wearing of protective equipment, such as helmets and masks. PMID- 1880213 TI - Teaching courses in clinical trial research methods. AB - This article describes nine separate elements that are part of any course: 1) the teachers, 2) the students, 3) expectations and attitudes of the teachers, 4) expectations and attitudes of the students, 5) a strategy of how to achieve the expectations, 6) materials to use, 7) types of presentations, 8) organizing the individual sessions, and 9) time and place for the course and each of its sessions. The relationship of each of these elements to a course on clinical trial research methods is discussed. Approaches to use for designing an overall curriculum for a school, company, or regulatory authority also are discussed. Sixteen separate courses are identified and briefly described. Several methods to enhance the effectiveness of individual lectures or discussions are mentioned. Potential courses, as well as those currently offered, should be periodically evaluated by all institutions that are involved in the area of clinical-trial research methods. PMID- 1880214 TI - The QAU: friend, not foe. PMID- 1880215 TI - Lovastatin therapy in hypercholesterolemia: effect on fibrinogen, hemorrheologic parameters, platelet activity, and red blood cell morphology. AB - The effect of lovastatin therapy on blood rheology was investigated in 26 hypercholesterolemic patients. Treatment with lovastatin was associated with a significant improvement in whole blood filtration time and a tendency toward normalization in red blood cell morphology. A significant increase was observed in fibrinogen level, in ADP-induced platelet aggregation, in the percentage of "big" platelets, and in platelet count. The viscosity of whole blood and plasma and the percentage of aggregated platelets did not change significantly. The cause for these hemorrheologic changes and their role in influencing the coronary risk of lovastatin-treated hypercholesterolemic patients should be further investigated. PMID- 1880216 TI - Effect of nifedipine on oxygen delivery in patients with angina pectoris: relation between blood viscosity and hematocrit. AB - The effect of nifedipine on blood viscosity and hematocrit was investigated. Blood was sampled from eight patients with angina pectoris (mean age: 59 +/- 8 yr) treated with nifedipine (20-30 mg/day) for 5 months. Using a cone-plate type viscometer, blood viscosity was determined at the shear rates of 37.5 and 375 sec 1 at 37 degrees C. Hematocrit was also measured at the same time. Since the ratio of hematocrit to blood viscosity at a shear rate of 375 sec-1 can be considered to reflect oxygen delivery, this ratio (oxygen delivery index) was also calculated. Blood viscosity at a shear rate of 37.5 sec-1 was significantly (P less than .05) decreased by nifedipine treatment, but hematocrit and the blood viscosity at a shear rate of 375 sec-1 were not changed. The oxygen delivery index, however, was significantly (P less than .01) increased after the administration of nifedipine. These results suggest that oxygen delivery increased by the treatment with nifedipine and inhibited erythrocyte aggregation by decreasing blood viscosity at low shear rate. PMID- 1880217 TI - Serum digoxin levels related to plasma propafenone levels during concomitant treatment. AB - Nine patients with supraventricular rhythm disorders were treated during 5-day periods with different oral doses (300, 450, 600, and 900 mg daily) of propafenone concomitantly to long-term digoxin treatment. A poor correlation (r = .398; P less than .05) was obtained when the difference between the mean digoxin serum level (calculated with the Cmin data determined each of the 5 days) observed during a given propafenone dose and the mean digoxin serum level observed before propafenone treatment, was correlated with the dose of propafenone; but an evident correlation (r = .778; P less than .01) was found when the difference in digoxin level was correlated with the plasma propafenone concentration. The propafenone effect of increasing digoxin blood levels was thus concluded to be poorly dose dependent but strongly concentration dependent. The association of propafenone to a long-term digoxin treatment can be considered with a low risk of toxicity when plasma propafenone concentration does not exceed about 1000 ng/mL. Propafenone plasma levels are unpredictable in view of their wide interindividual variation for a given dose, so their measurement is advised to detect high levels and consequently to prevent a rise in digoxin serum concentrations with the possibility of toxicity. In clinical practice, when propafenone concentration determinations are not readily available, digoxin serum levels at least have to be carefully monitored. PMID- 1880218 TI - Digoxin pharmacokinetics and spirapril, a new ace inhibitor. AB - As concurrent use of digoxin with the novel ACE inhibitor spirapril should be common, potential for spirapril to affect steady-state digoxin kinetics was studied. Fifteen healthy white male volunteers aged 22-42 and weighing 135-225 lbs took digoxin tablets 0.25 mg every 12 hours for 5 weeks. In crossover design, each also received spirapril or matching placebo capsules during weeks 1 and 2, or 4 and 5. Dosage of spirapril was increased from 12 mg to 48 mg once daily. Spirapril produced no significant effect on mean (+/- SD) serum digoxin concentration in the steady state, area under curve for 12 hours, peak digoxin level, time to peak, or urinary digoxin excretion over 12 hours. No change in renal or whole body digoxin clearance was seen. Unlike some other cardiovascular drugs, spirapril does not alter steady-state digoxin kinetics in healthy adults. PMID- 1880220 TI - Interactions of clonidine and nifedipine in moderately severe hypertensive patients. AB - In ten patients (age: 47-59 yr) with moderately severe essential hypertension, the humoral and hemodynamic effects of a 4-day therapy with 2 x 75 micrograms clonidine, 2 x 20 mg nifedipine (slow-release), and their combination were investigated and compared with baseline values. The following measurements were observed under clonidine (C), nifedipine (N), and on combination (C/N), respectively: heart rate fell significantly under C from a mean of 79 to 67/min (P less than .05), increased to 73/min after N (P greater than .05) and fell again to 68/min under combination (P less than .05). Systolic blood pressure (Riva-Rocci method) decreased from a mean of 184 to 171 (C), 168 (N) and 161 mm Hg (C/N), respectively (P less than .01). Diastolic blood pressure was also significantly altered (113 vs. 104 (C), 107 (N), and 100 mm Hg (C/N); P less than .05). Stroke volume (ECHO) was not altered significantly (77 vs. 71 (C), 79 (N), and 80 mL (C/N), respectively), whereas cardiac output dropped from 5.9 to 4.9 L/min (C; P less than .05), increased to 5.7 (N; P greater than .05), and dropped again to 5.3 L/min (C/N; P greater than .05). Peripheral vascular resistance increased from a mean of 2091 to 2297 (C), fell to 1933 (N), and increased again to 2138 dyn/sec/cm-5 (C/N). Plasma norepinephrine levels fell from 440 to 281 (C; P less than .01), increased to 391 (N; P greater than .05), and fell again to 404 pg/mL (C/N; P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880219 TI - Lecithin: cholesterol acyltransferase activity in familial hypercholesterolemia treated with simvastatin and simvastatin plus low-dose colestipol. AB - In 19 patients with heterozygous familial hypercholesterolemia (FH), the effects of simvastatin (S) 20 mg/d, 40 mg/d, and 40 mg/d plus low-dose colestipol (10 g/d) on plasma lipids, plasma lipoproteins, and plasma lecithin: cholesterol acyltransferase (LCAT) activity were investigated after an original dose-range escalation/descalation design. The drug regimen was changed every 8 weeks. A significant reduction in total cholesterol and LDL-cholesterol was observed, reaching 39% and 54% for the drug combination (week 28), and total apoprotein B and LDL-apoprotein B were reduced by 39% and 50%, respectively. Triglycerides were significantly lowered by S alone (up to 29% with 40 mg/d). HDL-cholesterol increased during therapy but the cholesterol content in HDL2-HDL3 fractions (isolated by ultracentrifugation) did not change significantly during the different steps. The ratio LDL-C/HDL-C fell by 57% at week 28. Plasma LCAT activity expressed as FER was significantly enhanced by S alone (+33%), and a further increase on drug combination regimen (+58%) was observed. This effect could be considered as a consequence of the increased fractional clearance of LDL C. It tended to be sustained during the descalation part of the study. Biochemical adverse effects were scarce and transient. In conclusion, the combination therapy increased the plasma LCAT/FER activity without a preferential enhancement in HDL2-C concentration. This original design allowed to define the most appropriate individual cholesterol-lowering drug dosage in FH patients. PMID- 1880221 TI - Evaluation of labetalol in elderly patients with essential hypertension. AB - Labetalol was evaluated in a multicenter, placebo-controlled study of elderly patients (greater than or equal to 60 years) with mild to moderate essential hypertension. After a placebo-washout period, doses were titrated from 100 mg BID to a maximum of 400 mg BID over a 6-week period. Once blood pressure control (standing diastolic blood pressure [SDBP] less than 90 mm Hg and greater than or equal to 10 mm Hg reduction from baseline) was achieved or the maximum allowable dosage had been given, the dosage remained the same until the end of the study. The titration phase was followed by a 4-week maintenance period. Blood pressure control was achieved in 37/54 (69%) of the patients who were treated with labetalol compared with 21/58 (36%) of the patients who received placebo (P less than .001). Twenty-nine (78%) of those controlled on labetalol responded to doses of 200 mg or less BID, and there was no significant difference between groups with respect to orthostatic blood pressure changes. Adverse experiences were generally mild and occurred with similar frequency in the labetalol and placebo groups; six patients who received labetalol and five who received placebo withdrew from the study due to adverse experiences, but in only one case (labetalol) was the adverse experience considered drug-related. In summary, labetalol effectively and safely lowered diastolic blood pressure in the elderly without producing significant orthostatic changes. PMID- 1880223 TI - Serum/saliva correlations for theophylline in asthmatics. AB - Theophylline levels in mixed saliva (both stimulated and unstimulated) were compared with total and free (unbound) serum theophylline levels in 28 asthmatic outpatients using theophylline regularly. Stimulated saliva predicted both total and unbound serum theophylline concentrations within +/- 1 microgram/mL in 62.5% and 92.9%, respectively, of the samples examined. In addition, the total serum levels could be used to predict unbound serum concentrations to within +/- 1 mg/L in 100% of the cases that were examined. These results indicate that saliva levels predict the unbound serum theophylline levels with greater accuracy and precision than they predict total serum theophylline levels. In addition, total serum levels can be used to reliably predict unbound serum levels. The use of mixed stimulated saliva is recommended as a reliable non-invasive method for monitoring unbound serum theophylline levels. The therapeutic range for saliva, which corresponds to the accepted total serum concentration range of 10-20 mg/L, is approximately 5.6-11.3 mg/L. PMID- 1880222 TI - Albuterol extended-release products: effect of food on the pharmacokinetics of single oral doses of Volmax and Proventil Repetabs in healthy male volunteers. AB - The absorption of albuterol from a single 4-mg oral dose of Volmax and Proventil Repetabs was investigated under both fasting and fed conditions in an open-label, randomized, four-period, crossover study in 24 healthy male volunteers. Blood was collected for determination of albuterol plasma concentrations by HPLC over 30 hours postdose. Twenty subjects were evaluable for data analysis. The mean Cmax for Volmax; administered after a meal was 19% lower than that of the drug administered in a fasting state (3.9 ng/mL vs. 4.8 ng/mL; P less than .01). An almost equivalent lowering of the mean Cmax (by 21%) was observed for Proventil Repetabs after administration with a meal versus fasting (4.2 ng/mL vs. 5.3 ng/mL; P less than .01). There were no significant differences between the two formulations in the degree of Cmax reduction due to the presence of food. The tmax occurred significantly later during the fed treatment for Volmax only (4.9 hours fasted vs. 6.4 hours fed; P less than .01). The lag time was significantly greater during the fed treatments for Volmax. No differences were observed in the area under the plasma concentration-time curve (AUC) for either formulation under fasting versus fed conditions, suggesting that the extent of absortion was not altered by food. Overall, food caused a more sustained release of albuterol from both Volmax and Proventil Repetabs. PMID- 1880224 TI - Alprazolam in end-stage renal disease: I. Pharmacokinetics. AB - In a double-blind, randomized, placebo-controlled study, the pharmacokinetics of alprazolam and its active metabolite, alpha-hydroxyalprazolam, were determined in 12 normal subjects and 12 dialysis patients [7 hemodialysis (HD) patients and 5 continuous ambulatory peritoneal dialysis (CAPD) patients]. Blood samples were collected over 48 hours after alprazolam 0.5 mg and alprazolam 2 mg administration. Alprazolam and alpha-hydroxyalprazolam concentrations and alprazolam free fraction were determined. The pharmacokinetics of alprazolam were similar in normal subjects and HD patients with the exception of higher free fraction in HD patients. Differences were detected, however, in the pharmacokinetics of alprazolam in CAPD patients when compared with normal subjects and HD patients. These differences included a higher free fraction and a lower apparent oral clearance and free clearance in CAPD patients than in normal subjects or in HD patients. There was also a tendency for a later Tmax and a longer elimination half-life in CAPD patients than in normal subjects or HD patients. Alpha-hydroxyalprazolam concentrations were less than 15% of corresponding alprazolam concentrations in normal subjects and dialysis patients. Thus, end-stage renal disease is associated with changes in absorption, distribution, and/or elimination of alprazolam. PMID- 1880225 TI - Comparison of adinazolam pharmacokinetics and effects in healthy and cirrhotic subjects. AB - The pharmacokinetics and pharmacodynamics of adinazolam were investigated in six patients with cirrhosis and six sex-matched control subjects. These subjects received a single 30-mg oral dose of adinazolam mesylate. Serial blood samples were collected for 24 hours after drug administration. Plasma was assayed for adinazolam and mono-desmethyl-adinazolam (NDMAD) concentrations by a specific HPLC technique. Pharmacokinetic parameters were estimated by noncompartmental methods. Psychomotor effects of adinazolam were assessed using a digit-symbol substitution test (DSST) and aiming test (AIM). Memory effects were assessed by a modification of the Randt memory test (MEM); sedation was assessed using an observer-rated scale. Differences in pharmacokinetics of the parent drug were noted: adinazolam oral clearance was lower in patients with cirrhosis (35.0 +/- 27.9 L/hr) than in normal subjects (73.7 +/- 22.1 L/hr; P = .024); Kel was significantly lower in patients with cirrhosis (.126 +/- .084 vs. .278 +/- .070; P = .007), whereas the mean t1/2 in patients with cirrhosis was 7.70 hours as compared with 2.67 hours in normal subjects. Cmax was higher in the group with cirrhosis (266 +/- 95.5 vs. 153 +/- 29.3 ng/mL; P = .019). For NDMAD, Kel was lower in cirrhotic subjects and resulted in a prolonged t1/2 in cirrhotic subjects compared with normal subjects (6.70 vs. 3.79 hr; P = .0152). NDMAD AUC tended to be higher in cirrhotic subjects (1515 +/- 254 vs. 1162 +/- 254 ng.hr/mL; P = .064). No significant differences were noted in psychomotor performance, memory, or sedation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880226 TI - A milestone in clinical pharmacology. PMID- 1880227 TI - Gender-related differences in xenobiotic metabolism. PMID- 1880228 TI - Role of the General Clinical Research Center in teaching clinical management. PMID- 1880229 TI - Pharmacokinetics of felodipine in chronic hemodialysis patients. AB - Five chronic hemodialysis patients (1 woman and 4 men, aged, 46-68 yr) were given an oral dose of 10 mg felodipine followed by 0.057 mg [3H] felodipine IV. After 5 hours, a hemodialysis treatment lasting 4 hours was performed. Blood and dialysate flows were 200 mL/min and 500 mL/min, respectively. Capillary dialyzers with 1.3 m2 cellulose acetate membrane were used. The pharmacokinetic characteristics and reduction in diastolic BP were similar to those in hypertensive patients with normal renal function and in uremic patients who were not treated with dialysis. There was no measurable removal of felodipine by hemodialysis. Dialyzer clearance of radioactive metabolites was about 10 mL/min, and only 8.9% of the dose was eliminated by the treatment. The half-life of radioactive metabolites was 10 days (6-14 days) in three patients dialyzed thrice weekly. Since the metabolites are biologically inactive, no adjustment of dose is required in hemodialysis patients. PMID- 1880230 TI - Efficacy of cardioselective beta-adrenergic blockade with intravenously administered metoprolol in the treatment of supraventricular tachyarrhythmias. AB - The efficacy of intravenously administered metoprolol, a cardioselective beta adrenergic blocking agent, was evaluated in the treatment of supraventricular tachyarrhythmias in 16 patients. The arrhythmias that were treated were atrial fibrillation (11 patients), atrial flutter (2 patients), supraventricular tachycardia (2 patients), and multifocal atrial tachycardia (1 patient). Mean dose of metoprolol was 9.5 mg (range: 2-15 mg) administered in one or two separate infusions of up to 7.5 mg each over a cumulative maximum interval of 25 minutes. In the 13 responders (81%), mean ventricular rate decreased from 134 +/- 6 to 106 +/- 7 beats/min 10 minutes after metoprolol administration and was controlled for 40 to 320 minutes without further therapy. Minimum ventricular rate (98 +/- 6 beats/min) was reached 48 minutes after initiation of metoprolol. Metoprolol reduced ventricular rate by greater than 15% (decrease of 26-60 beats/min) in 11 (69%) of 16 patients, including 9 (82%) of 11 patients with atrial fibrillation. In two other patients, one with atrial fibrillation and one with supraventricular tachycardia, ventricular rate was reduced by greater than 12%. Hypotension, occurring in five patients, was the most frequent side effect but was transient and readily managed. Cardioselective beta-adrenergic blockade by metoprolol was rapidly effective in controlling ventricular rate in a majority of patients with supraventricular tachyarrhythmias and may be of particular use in selected patients with chronic obstructive pulmonary disease in whom intravenous beta-adrenergic blockade is indicated. Hypotension is an important potential side effect. PMID- 1880231 TI - Pharmacokinetics of ceftriaxone in liver-transplant recipients. AB - The disposition of ceftriaxone was studied after a single 2 g intravenous dose in seven patients 3 to 5 days after liver transplantation. Ceftriaxone concentrations in plasma, urine, and bile were measured by HPLC, and plasma protein binding was determined by equilibrium dialysis. Plasma protein binding was nonlinear, and the unbound fraction varied between 0.05 and 0.56. Both capacity and affinity were markedly different from reported values for normal subjects. The pharmacokinetic parameters obtained were: total body clearance (TBC), 11.2 +/- 7.8 mL/hr/kg total and 44.8 +/- 29.1 mL/hr/kg unbound; volume of distribution (V(area)), 224 +/- 76 mL/kg total and 767 +/- 432 mL/kg unbound; steady-state volume of distribution (Vss), 212 +/- 68 mL/kg total and 651 +/- 368 mL/kg unbound; terminal disposition half-life (t1/2), 21.6 +/- 14.3 hour total and 16.3 +/- 11.1 hour unbound. TBC for both total and free drug was considerably lower than literature values for normal subjects. V(area) for total drug was greater than normal, whereas the corresponding value for free drug was smaller than normal. The plasma ceftriaxone concentrations at 12 and 24 hours were above the reported minimum inhibitory concentration (MIC). The fraction of the administered dose excreted in urine over 24 hours was 38 +/- 29% and did not differ markedly from that reported for normal subjects. Less than 2% of the administered dose was excreted in 24-hour bile; however, biliary concentrations were always above MIC. Ceftriaxone can be administered once or twice daily at a dose of 2 g/day for prophylaxis in liver transplant recipients. PMID- 1880232 TI - A new clinical bioassay for antipyresis. AB - Three studies that describe antipyretic bioassay are detailed. Reference Standard Endotoxin (RSE) was used to induce fever in healthy male volunteers under randomized, single-dose, double-blind, parallel, and standard drug-control conditions. Thirty minutes before administering RSE, the subjects were medicated with test drug, and oral temperatures were recorded every 15 minutes for 6 to 8 hours. Two NSAIDs and a centrally acting analgesic were evaluated. Both doses of a propionic derivative, three high doses of tebufelone (a new NSAID), as well as the high dose of flupirtine effectively obtunded the fever response to RSE. Adverse reactions consisting of flu-like symptoms such as myalgia, headache, and chills were also significantly reduced with the standard as well as test drugs. The authors conclude that the RSE model is a quick, safe, and reliable method to evaluate antipyresis and to predict other pharmacologic effects of these types of drugs, such as analgesia. PMID- 1880233 TI - Hypnotic efficacy of estazolam compared with flurazepam in outpatients with insomnia. AB - Estazolam is a new benzodiazepine hypnotic agent with an intermediate half-life of 12 to 15 hours. The authors designed an investigation to compare its hypnotic efficacy to that of flurazepam, generally considered the reference standard. The hypnotic efficacy of estazolam at two doses (1 mg and 2 mg) was compared with that of flurazepam (30 mg) in a double-blind, placebo-controlled, multicenter, 7 night study that involved 223 outpatients with insomnia. On subjective assessments of the patients, no differences were noted between estazolam 2 mg and flurazepam 30 mg on any of six sleep parameters. Patients who were receiving estazolam 1 mg rated their sleep significantly better than did patients who were receiving placebo on all parameters except sleep latency. Global evaluation of the physicians indicated significant improvement in quality of sleep, sleep depth, sleep duration, and nocturnal awakenings in all three active treatment groups; estazolam 2 mg and flurazepam also decreased sleep latency significantly. The percentage of patients who reported any adverse experience was 68% for flurazepam, 58% for estazolam 2 mg, and 54% for estazolam 1 mg; the incidence of adverse events in the placebo group was 43%. In conclusion, estazolam 2 mg was found to be as effective a hypnotic as flurazepam 30 mg. Estazolam 1 mg is also effective in the treatment of outpatients with insomnia, but to a lesser degree. PMID- 1880234 TI - A double-blind, randomized, placebo-controlled comparison of the metabolic effects of low-dose hydrochlorothiazide and indapamide. AB - To compare the metabolic effects of indapamide (I) and hydrochlorothiazide (HCTZ) at equivalent hypotensive doses, 11 hypertensive patients (5 male, 8 black, aged 56 +/- 8 yr--mean +/- SEM) having serum uric acid concentrations greater than 8.0 mg/dL while receiving previous therapy with thiazides, received 28-day courses of placebo, indapamide (2.5 mg/d), and HCTZ (25 mg/d) in randomized, double-blind, double-crossover design. Supine and standing blood pressures, weight, pulse rates and sera were obtained after each 28 day period. Blood pressures and weights were lowered (P less than .001 and 0.01, respectively) equally by the diuretics: supine blood pressures fell from 168 +/- 4/104 +/- 2 (placebo) to 153 +/- 4/93 +/ 2 (HCTZ) and 155 +/- 4/94 +/- 2 mm Hg (I); standing blood pressures (after 2 minutes upright) also decreased: 171 +/- 5/104 +/- 2 (placebo) to 156 +/- 5/93 +/ 2 (HCTZ) and 157 +/- 4/94 +/- 2 mm Hg (I). There was a statistically significant difference (P less than .05) across treatments by analysis of variance in both uric acid and potassium concentrations: serum urate (in mg/dL) was lowest with placebo (7.1 +/- 0.3), and rose to 8.3 +/- 0.2 with HCTZ (P less than .001 compared with placebo by paired t test), and 8.1 +/- 0.2 with I (P less than .005 vs. placebo). The urate concentration with I was significantly lower than that with HCTZ (P less than .02), but the magnitude of the difference was small (0.2 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880235 TI - Hair anatomy for the clinician. AB - The rational evaluation of hair disorders requires familiarity with follicular anatomy. Hair structure can be easily examined by studying clipped hair shafts, entire hairs gently pulled or forcibly plucked from the scalp, and scalp biopsies (sectioned vertically or transversely). Anatomic features will be different depending on whether a given hair is in the anagen, catagen, or telogen phase. Follicle size will also vary, from the minute vellus hair to the long, thick terminal hair. Each follicle can be divided into distinct regions--bulb, suprabulbar zone, isthmus, and infundibulum. Activity growing (anagen) hairs are characterized by a hair matrix surrounding a dermal papilla; inner and outer root sheaths are present and well developed. A catagen hair can be identified by its markedly thickened vitreous layer and fibrous root sheath, which surrounds an epithelial column; above this column, the presumptive club forms. A telogen hair is distinguished by its fully keratinized club, which is surrounded by an epithelial sac. Below this lies the secondary hair germ and condensed dermal papilla, waiting for the mysterious signal that initiates a new life cycle. PMID- 1880236 TI - Pyoderma gangrenosum in infancy: the youngest reported patient. PMID- 1880237 TI - Livedo reticularis developing simultaneously with a syncopal attack in a patient with atrial myxoma. PMID- 1880238 TI - Telogen effluvium associated with eosinophilia-myalgia syndrome. PMID- 1880239 TI - Erythema nodosum in HIV-infected patients. PMID- 1880240 TI - Reticulate acropigmentation of Kitamura with localized alopecia. PMID- 1880241 TI - Generalized lichen spinulosus in an HIV-positive man. PMID- 1880242 TI - Dermatology residency training in 1932 versus dermatology residency training in 1990. AB - Dermatologic training programs and patient care in 1932 are compared with patient care, research, and residency training programs in 1990. The changes are due to development of newer diagnostic procedures and therapeutic agents, emergence of dermatopharmacology programs, research conducted by and supported by the pharmaceutical industry, and support of cutaneous research by the government. The excellence of teaching and patient care in 1932 was due to the "giants" who created interest in dermatology and by their dedication and ingenuity managed recalcitrant dermatoses without presently available drugs, chemotherapeutic agents, diagnostic techniques, basic information, and advances in cutaneous surgery. PMID- 1880243 TI - Clinical research in dermatology: can we achieve our potential? PMID- 1880244 TI - Dermatology awake--dermatopathology is in peril. PMID- 1880245 TI - Urticarial lesions and Lyme disease. PMID- 1880246 TI - Determination of UVA protection. PMID- 1880247 TI - Anticardiolipin antibodies in systemic sclerosis. PMID- 1880248 TI - Method to determine UVA protection for normal skin. PMID- 1880249 TI - Cutaneous manifestations of cryoglobulinemia: clinical and histopathologic study of seventy-two patients. AB - In the 72 cases of cryoglobulinemia reviewed, erythematous to purpuric macules or papules were present in 92%. Infarction, hemorrhagic crusts, and ulcers were present in 10% to 25% of the patients and were relatively more common in type I cryoglobulinemia than in the other types. Postinflammatory hyperpigmentation was noted in 40%. Lesions on the leg were common in all types of cryoglobulinemia; however, lesions on the head and mucosal surfaces suggested type I cryoglobulinemia. Histopathologic features were classified as vasculitis in 50%, inflammatory or noninflammatory purpura in 15%, noninflammatory hyaline thrombosis in 10%, and postinflammatory sequelae in 10%. Noninflammatory hyaline thrombosis was relatively more frequent in type I. Thus erythematous to purpuric lesions on the legs and leukocytoclastic vasculitis are the common cutaneous findings in cryoglobulinemia. Type I cryoglobulinemia is suggested by noninflammatory hyaline thrombosis, cutaneous infarction, hemorrhagic crusts, skin ulcerations, and lesions of the head and neck and of oral or nasal mucosa. PMID- 1880250 TI - Studies of laminin and type IV collagen in blisters of porphyria cutanea tarda and drug-induced pseudoporphyria. AB - Blisters from five patients with porphyria cutanea tarda and two patients with drug-induced pseudoporphyria were examined by direct immunofluorescence and by immunofluorescence mapping with antibodies against laminin and type IV collagen to determine the level of subepidermal separation. Primary screening by direct immunofluorescence revealed the characteristic immune deposits in the vessel walls of the upper dermal plexus in all cases and at the dermoepidermal junction in five of seven cases. Type IV collagen and laminin were reactive in six and five cases, respectively, and appeared in the floor of the bulla. The findings were identical in porphyria and pseudoporphyria. In one case in which the bullous pemphigoid antigen could be detected, it appeared in the epidermal roof of the bulla. These findings indicate that the split in porphyria and pseudoporphyria occurs in the lamina lucida. We propose that a multistep mechanism involved in the induction of blisters may be similar in porphyria and pseudoporphyria. PMID- 1880251 TI - Cutaneous lymphomas of phenotypically undetermined lineage: contribution of genotypic analysis. AB - Genotypic analyses were performed in six primary cutaneous lymphomas whose lineage could not be assessed on the basis of histologic and phenotypic data. By immunophenotyping, these neoplasms expressed leukocyte common antigen and HLA-DR but did not show consistent immunostaining for B-cell or T-cell differentiation antigens. Expression of nonspecific histiocytic markers such as lysozyme and alpha 1-antitrypsin was found in three cases. By genotyping, three cases retained a germline configuration and immunoglobulin gene rearrangement was observed in one case, T-cell receptor gene rearrangement was found in one case, and both types of rearrangements in one case. Of the three patients in whom gene rearrangements were noted, two rapidly died and the other patient, with a dual genotype, is still alive 15 years after diagnosis. The three patients without gene rearrangements are alive and well after a mean follow-up of 2.5 years. It appears that cutaneous lymphomas with an uncertain phenotype include at least some cases of authentic B-cell or T-cell lymphomas. The germline configuration that we observed in cases with a chronic course remains difficult to explain. It may be related to a low malignancy form of histiocytic lymphoma, an atypical polyclonal hyperplasia, or even a low-grade lymphoma arising from a primitive cell without established commitment to either B- or T-cell lineage. PMID- 1880252 TI - The effect of electrical stimulation on the number of mast cells in healing wounds. AB - Many cutaneous disorders are associated with activation or increased numbers of mast cells. Electrical stimulation has been shown to be effective in treating many of these disorders. This study is designed to examine the effect of electrical stimulation on mast cells in acute wounds. Four pathogen-free pigs received 20 wounds, each of which was subjected to biopsy at various times after wounding. Half of the wounds were treated with electrical stimulation and the other half were treated with a sham electrode. The biopsy specimens were fixed in Carnoy's medium and stained with alcian blue and Nuclear Fast Red. Mast cells from both sets of wounds were counted and analyzed. Highly significant reductions in the number of mast cells were seen with electrical stimulation on days 1 and 2 compared with nonstimulated control wounds. Electron microscopy was performed to compare the stimulated and control mast cells for characteristic features in morphology, location, and evidence of degranulation. Electrical stimulation did not appear to induce degranulation. The ability of electrical stimulation to decrease the number of mast cells may be related to a reduction of either proliferation or migration of these cells and may prove to be a valuable therapeutic technique. PMID- 1880253 TI - Nonhealing leg ulcers: a manifestation of basal cell carcinoma. AB - Seven patients with basal cell carcinomas presenting as nonhealing ulcers are reported. The importance of considering malignancy and taking biopsy specimens of leg ulcers that fail to respond to treatment is emphasized. PMID- 1880254 TI - Serum aminoterminal propeptide of type III procollagen in psoriasis and psoriatic arthritis: relation to liver fibrosis and arthritis. AB - Levels of serum aminoterminal propeptide of type III procollagen were measured in 170 patients with psoriasis (49% with coexistent psoriatic arthritis) who had liver biopsies performed during or before treatment with methotrexate or, in some cases, with retinoids. Psoriasis patients with fibrosis or cirrhosis in their liver biopsy specimens had a significantly higher mean serum aminoterminal propeptide of type III procollagen than did patients without fibrosis and without arthritis. Only 4% of patients without cirrhosis or fibrosis and no arthritis had an elevated serum aminoterminal propeptide of type III procollagen. In contrast, 38% of patients with psoriatic arthritis had an increased aminoterminal propeptide of type III procollagen in the absence of detectable liver fibrosis. It is concluded that the number of liver biopsies performed on methotrexate treated psoriasis patients with or without arthritis may be reduced to a minimum as long as serum aminoterminal propeptide of type III procollagen is normal. Increased serum aminoterminal propeptide of type III procollagen in the absence of arthritis is a strong indicator of liver fibrogenesis and suggests the need for liver biopsy to monitor possible methotrexate-induced toxicity. In patients with psoriatic arthritis an increased aminoterminal propeptide of type III procollagen may be related to the joint disease. Patients with psoriatic arthritis and increased levels of aminoterminal propeptide of type III procollagen should therefore follow the established guidelines for the use of methotrexate in psoriasis. PMID- 1880255 TI - Papular mucinosis in L-tryptophan-induced eosinophilia-myalgia syndrome. AB - Five patients with the L-tryptophan-related eosinophilia-myalgia syndrome had a generalized eruption of flesh-colored papules. In all patients, histologic examination revealed a focal accumulation of mucin in the upper mid dermis, associated with increased dermal cellularity. The mucin was composed predominantly of hyaluronic acid, with small amounts of sulfated acid mucopolysaccharides. The cells within the lesion were fibroblasts. The lesions slowly regressed after L-tryptophan was discontinued. Proposed explanations for the L-tryptophan-related eosinophilia-myalgia syndrome have centered on contaminants, chemically related to L-tryptophan, introduced in the manufacturing process. Tryptophan metabolites have been linked with sclerotic cutaneous diseases but have not been previously implicated in cutaneous mucinoses. PMID- 1880256 TI - Photopatch testing: the 5-year experience of the German, Austrian, and Swiss Photopatch Test Group. AB - A cooperative photopatch test study was conducted by 45 dermatologic centers in Austria, Germany, and Switzerland. Results obtained from 1985 to 1990 are presented. A standard photopatch test tray of 32 substances was applied to the back of patients with suspected photosensivity. After applications for 24 hours, test sites were irradiated with 10 joules/cm2UVA. Unirradiated controls were included. Readings were performed immediately and 24, 48, and 72 hours after irradiation; responses were qualitatively graded on a 4-point scale. All data were stored and processed by a computer. With computer-assisted analysis of reaction patterns photoallergic reactions were identified and distinguished from phototoxic reactions. Data of 1129 patients were evaluated. Among a total of 2859 positive test reactions in 870 patients, 2041 in 778 patients were found to be photoinduced and 818 in 413 patients were contact reactions; 108 reactions in 83 patients were classified as photoallergic. Nonsteroidal anti-inflammatory drugs, disinfectants, sunscreens, phenothiazines, and fragrances caused most often photoallergic reactions. Many unspecific phototoxic reactions were induced by tiaprofenic acid, promethazine, carprofen, chlorpromazine, fenticolar, wood balsam of Peru, and perfumes. Despite the distinction between photoallergic and phototoxic responses, many test reactions lacked relevance for the patients' dermatoses. PMID- 1880257 TI - Toxic epidermal necrolysis: a review. AB - This article reviews the many facets of toxic epidermal necrolysis. Emphasis is placed on the importance of early diagnosis, burn unit placement, supportive care, and avoidance of systemic steroids. Discussion also includes other therapeutic options and the pathophysiology of the disease. PMID- 1880258 TI - Studies on the cellular origin of neurothekeoma: clinical, light microscopic, immunohistochemical, and ultrastructural observations. AB - The clinical, histopathologic, and immunohistochemical features of 11 cases of neurothekeoma are reported. One case was examined by electron microscopy. The mean age of the patients was 27.1 years; the study comprised eight female and three male patients. Most lesions were nondescript papules and located on the upper part of the body, seven cases of neurothekeoma on the head. Eight cases were classified as cellular neurothekeoma on the basis of a striking fascicular pattern and three cases as myxomatous neurothekeoma because of prominent myxoid stromal change. All cellular neurothekeomas failed to express S-100 protein, whereas the three myxomatous types were strongly positive for this marker. Other than vimentin, there was no significant immunoreactivity with other immunohistochemical markers. Ultrastructural study of one case of cellular neurothekeoma was inconclusive for cell type although a perineurial origin could not be excluded. On the basis of these results, we conclude that cellular neurothekeoma differs from myxomatous neurothekeoma not only by clinical and histologic findings but also by immunoreactivity with S-100 protein. These findings also suggest the existence of two distinct subtypes of neurothekeoma and possible origin of the two variants of neurothekeoma from different cell types or at least variation in phenotypic expression of a common cell type. On the other hand, it cannot be excluded that these two variants are different stages in the natural history of neurothekeoma. PMID- 1880259 TI - What dermatologists should know about digital imaging. AB - The digital imaging revolution that swept other medical specialties in the late 1970s and early 1980s is beginning to find new and important roles in dermatology. This technology has a wide range of educational, clinical, and research applications. Dermatologists should understand certain basic concepts about images and imaging techniques to take advantage of progress in this field and eventually apply it to their own research and/or clinical practice. PMID- 1880260 TI - Evaluation of methods for the diagnosis of Streptococcus agalactiae intramammary infections in dairy cattle. AB - The sensitivity, specificity, and positive and negative predictive values were compared for six methods of collecting or culturing milk samples for the diagnosis of chronic Streptococcus agalactiae intramammary infection. Cows in four dairy herds were cultured three times in 2 wk to determine infection status. At the second sample period, individual quarter and composite milk samples were taken before and immediately after milking, and two volumes of milk from the composite samples were streaked on culture plates. The sensitivity, specificity, and predictive values for these cultures ranged between 95 and 100% for all diagnostic methods, and no significant differences were found between methods. The results indicate that when either quarter or composite samples are collected before or immediately after milking, 95 to 100% of S. agalactiae culture-positive cows will be infected with S. agalactiae in herds with a prevalence of S. agalactiae between 35 and 55%. A similar proportion of culture-negative cows will be uninfected. PMID- 1880262 TI - N-acetyl-beta-D-glucosaminidase, etiologic agent, and duration of clinical signs for sequential episodes of chronic clinical mastitis in dairy cows. AB - This study examined effects of repeated episodes of clinical mastitis in chronically infected quarters on milk N-acetyl-beta-D-glucosaminidase activity and duration of clinical signs. Milk samples were collected at each clinical onset from 49 chronic mastitis cases on a 1700-cow Michigan dairy farm. There were 49 first episodes of clinical mastitis, 49 second episodes, and 13 episodes of third or more. Agents isolated were Staphylococcus aureus (18.4%), Staphylococcus (7.3%), no growth (20.2%), environmental pathogens (streptococci other than agalactiae, Escherichia coli, Klebsiella spp., Enterobacter spp., and Citrobacter spp.) (22.0%), other pathogens (Serratia spp., Bacillus spp., diphtheroids [Corynebacterium spp. and Actinomyces pyogenes], Pseudomonas spp., and Nocardia spp.) (11.9%), mixed pathogens (two agents isolated) (12.8%), and contaminated samples (7.3%). Etiologic agents, duration of clinical signs, and NAGase did not differ by episode number. The correlation between log of NAGase and log of time until clinical recovery was .34. The relationship between NAGase and duration of clinical signs was strongest for second episodes, and weakest for third and greater episodes of chronic mastitis. PMID- 1880261 TI - Endotoxin mastitis in cows milked four times daily. AB - As part of a project to identify the pathophysiological cause or causes of mastitic hypogalactia, midlactation cows were infused in two homolateral quarters with 10 micrograms of endotoxin while being milked four times daily to resolve better the temporal changes in mammary synthetic activity during endotoxin mastitis. Milk fat was decreased by the first milking (5 h) postinfusion and then recovered rapidly. In contrast, milk yield and the yields of protein and lactose were not significantly inhibited until the second milking, and these yields recovered slowly thereafter. The decline in milk yield by infused quarters was only 20% greater than the decline by uninfused quarters in this experiment. Mammary inflammation developed rapidly in infused quarters as milk serum albumin concentration was maximal at the first milking. Milk SCC and NAGase were also elevated at this time, and maximal levels occurred at milkings 2 to 4. Increased temperature, increased cortisol, and a mild anorexia were apparent at the first milking only. Endotoxin treatment had no effect on serum prolactin or glucose. These data suggest that the delayed hypogalactia is consequent to the mammary inflammation and systemic responses following endotoxin infusion. The results indicate that different pathophysiological events may inhibit synthesis of the different milk components. PMID- 1880263 TI - Isolation of Staphylococcus aureus from sites other than the lactating mammary gland. AB - The body sites of 163 heifers, bedding and feedstuff samples, flies, and hands and nares of the research personnel were sampled in order to determine the sources of Staphylococcus aureus in a dairy herd other than the lactating mammary gland. Lesions on the udder of lactating animals and the air in the milking parlor were also sampled. Staphylococci isolated from bedding samples were identified as to species. Staphylococcus aureus was isolated from all sources examined except flies. An enrichment procedure was necessary for isolating S. aureus from two bedding samples although other Staphylococcus species were present in high numbers. The designation "environmental staphylococci" is proposed for Staphylococcus species that were apparently free-living in the environment. PMID- 1880264 TI - Mastitis prevalence in primigravid heifers at parturition. AB - Prevalence of intramammary infection was determined for 382 primigravid heifers within 3 d postpartum on 11 Vermont dairy farms. Data collected during a 5-yr period are summarized. Duplicate quarter milk samples were cultured on tryptose blood agar plates containing .1% esculin. Intramammary infections were diagnosed in 45.5% of the heifers and 18.7% of quarters. Staphylococcus species were the most prevalent bacteria isolated: they appeared in 25.4% of the heifers and 12.1% of quarters. Only 2.6% of the heifers were diagnosed with Staphylococcus aureus; 22.8% had udder infection caused by other staphylococcal species. Environmental mastitis pathogens, coliforms, and streptococci other than Streptococcus agalactiae were isolated from 14.9% of the heifers and 4.8% of quarters. The prevalence of mastitis among these primigravid heifers at parturition indicates a need to improve methods of diagnosis and control programs. PMID- 1880265 TI - Variation in somatic cell count, California mastitis test, and electrical conductivity among various fractions of ewe's milk. AB - Variation of three estimates of udder inflammation (SCC, California mastitis test, and electrical conductivity) among the foremilk, machine milk, and hand stripping samples were studied. Foremilk and hand stripping milks were taken from each individual teat; machine milk was taken from the entire udder. For this experiment a total of 30 Manchega ewes were subjected to machine milking during the 9th wk of lactation. Samples were taken in duplicate during two milkings on consecutive mornings. Significant differences were observed in the SCC and electrical conductivity, but not in California mastitis test, between foremilk and stripping milk. The stripping fraction had higher SCC (70 +/- 12%) and lower electrical conductivity (difference = .52 +/- .03 mS/cm) than did the foremilk fraction in both healthy and mastitic udders. Machine milk, foremilk, and stripping milk fractions in udders where both halves were healthy were compared. The electrical conductivity values for the machine milk were intermediate and significantly different from conductivity of foremilk and stripping fractions. The log SCC of the machine milk did not differ from that of the foremilk fraction but was significantly less than the stripping milk. PMID- 1880266 TI - Temporal patterns of lost milk production following clinical mastitis in a large Michigan Holstein herd. AB - Cows with three hundred and sixteen cases of clinical mastitis were sampled by microbiologic culture during a 6-mo period on a 1700-cow Michigan Holstein dairy farm. Daily milk weights were obtained on all cows before clinical onset and for 60 d after onset. Predicted post-mastitis production, projected on the basis of premastitis production and the lactation curves of contemporary non-mastitic herdmates, was compared with actual daily milk production during the 60 d following clinical onset. Cows experiencing clinical mastitis produced approximately 341 kg less salable milk during the 60 d after clinical onset compared with projected production. This milk loss included both decreased production and milk withheld from market following antibiotic treatment. Pluriparous cows lost 2.06 times as much milk as first lactation cows, and cows with mastitis occurring before 150 d in lactation lost 1.40 times as much milk when compared with other cows. Cows with mastitis occurring in the winter showed a milk loss 1.37 times greater than cows with mastitis in summer. The identity of the mastitis agent isolated from the clinical case was not strongly associated with the drop in milk production in the 60 d following clinical onset. PMID- 1880267 TI - Effect of calf housing on plasma ascorbate and endocrine and immune function. AB - The effect of housing calves in indoor metal pens (1.2 m x 1.2 m) or commercial calf hutches was determined on plasma concentration of cortisol, antibodies, and ascorbate. Six calves per treatment were deprived of colostrum, assigned randomly to treatment, and fed a commercial milk replacer until 56 d of age. Calves housed in hutches had higher plasma IgG concentrations than calves in pens at 42 and 56 d of age. Housing had no effect on plasma IgM concentration. Antibody titers to keyhole limpet hemocyanin injected at 14 and 28 d of age were higher in hutch housed calves from 21 to 56 d of age. Calves housed in hutches also had lower plasma cortisol concentrations, although cortisol decreased with age in both treatment groups. Plasma ascorbate and ascorbate plus dehydroascorbate were higher in hutch-housed calves. Regression analysis indicated a positive relationship between plasma ascorbate and IgG in metal penhoused calves and a negative relationship in hutch-housed calves. Housing in 1.2 m x 1.2 m metal pens decreases cortisol, plasma ascorbate, IgG, and specific antibody titers in dairy calves relative to calves housed in hutches. PMID- 1880268 TI - Serum immunoglobulin profiles of dairy cows chronically treated with recombinant bovine somatotropin. AB - The objective of this study was to determine the effects of exogenous somatotropin on blood profiles of the major bovine Ig isotypes. Holsteins were treated with either 0, 10.3, or 20.6 mg recombinant bST/d. Subcutaneous injections were started between wk 4 and 5 of lactation and continued for 266 d. Blood samples were collected by coccygeal venipuncture throughout lactation for serum IgG, G1, G2, A, and M concentration determination. Cows treated with 10.3 mg of bST/d exhibited modest increases in mean blood concentrations of IgG (12.4%) and IgG2 (18.4%) relative to the other groups of cows. In addition, treated cows had 10.1% higher average concentration of IgA than controls. Somatotropin did not influence average lactational concentrations of IgG1 or IgM, although the group receiving 10.3 mg/d had higher late lactation concentrations of IgG1 than did the other two groups. However, treatment mean isotype concentrations were always within normal ranges, except for IgG2 from the 10.3 mg/d group, which were higher. The practical significance of elevated serum Ig concentrations observed in the present study is not known. However, the present data do show that bST administered at doses that increased milk yield had no apparent detrimental effect on humoral immunity as measured by blood concentrations of Ig. PMID- 1880269 TI - Influence of rumen undegradable protein levels on feed intake and milk production of dairy cows. AB - Twenty-seven dairy cows in midlactation were utilized in two experiments using 15 and 12 cows to determine effects of varying the delivery of ruminally undegraded protein on feed intake, milk production, and some rumen and plasma characteristics. In Experiment 1, cows consumed alfalfa silage ad libitum and one of three barley-based concentrates with either soybean meal (a rapidly rumen degraded protein source), corn gluten meal (a slowly degraded protein source), or an equal mixture of the two, fed at the rate of .36 kg/kg of milk produced. In Experiment 2, cows were fed total mixed diets based upon alfalfa silage, barley, and either soybean meal, corn gluten meal, or a mixture of soybean meal and whey powder (a protein source very rapidly degraded in the rumen). In sacco incubation procedures were used to estimate degradability of protein in all diets. All diets exceeded Agricultural Research Council recommendations for rumen degraded and undegraded protein as well as NRC recommendations for degraded protein. However, one to three of the six total diets, depending upon assumed ruminal turnover rates, did not meet NRC recommendations for undegraded protein. Production parameters, include DMI as well as milk yield and composition, were not influenced by diet in either experiment. Results do not support NRC recommendations for ruminally undegraded protein for midlactation dairy cows producing about 30 kg/d of milk and broadly support the lower recommendations of the Agricultural Research Council. Results also appear to question use of dietary energy intake to predict net rumen microbial protein yield. PMID- 1880270 TI - Effect of dietary rumen-protected choline in lactating dairy cows. AB - Two experiments were conducted to test the effects of graded amounts of rumen protected choline on milk yield and composition in lactating dairy cows fed 40% corn silage and 60% concentrate diets (DM basis). In Experiment 1, 48 Holstein cows were fed 0, .078, .156, and .234% rumen-protected choline (choline chloride basis) from wk 5 to 21 postpartum. Increasing choline had no effect on DMI and tended to increase milk yield only from 1 to 2.2 kg/d. Milk fat percentage was reduced in the .078% choline treatment and increased to control levels thereafter with .156 and .234% choline. In Experiment 2, 16 Holstein cows in midlactation were assigned randomly to either 13.0 or 16.5% dietary CP (DM basis). Within CP concentration, cows were fed 0, .08, .16, and .24% rumen-protected choline in a replicated 4 x 4 Latin square design. Dietary protein had no effect on milk yield, although milk protein percentage and yield were increased .25 percentage units and 63 g/d, respectively, by increased dietary CP. Increasing dietary choline to .24% linearly increased milk yield 2.6 kg/d, although it had no consistent effects on milk fat or protein percentage. There was only a slight tendency for greater responses in milk yield to dietary choline with lower dietary CP. Data from these experiments confirm earlier results with postruminal choline infusions, suggesting that choline may be a limiting nutrient for milk production. PMID- 1880271 TI - Detection of bovine somatotropin treatment in dairy cattle performance records. AB - Effectiveness of cluster analysis in detecting application of bST was examined. Field data were manipulated by adding a specified percentage of the true performance to original test day records to simulate application of bST. The partly manipulated data then were analyzed using cluster analysis. Test day milk production data came from 42,779 cows of the Bretagne (Northwestern France) that had test days between 1986 and 1989. As criteria in the cluster analysis for differentiation between treated and untreated cows, parameters of the incomplete gamma function along with other variables calculated from test day records were used. The best differentiation was achieved when a persistency parameter, defined as the ratio of second divided by first trimester production, was used as a variable in the cluster analysis. For the assumed scenario of bST application, more than 80% of all cows were classified correctly under random use of bST. Systematic treatment led to improved results. PMID- 1880272 TI - Genotype by environment interaction for Holstein milk yield in Colombia, Mexico, and Puerto Rico. AB - Components of (co)variance and genetic parameters were estimated by REML procedures from first lactation mature equivalent Holstein milk records from 54,604 Colombian, Mexican, and Puerto Rican cows and 198,079 US cows. The objective was to determine the cause of heterogeneous daughter response to sire selection for milk yield between the regions. Data from Latin America were partitioned by country and by herd-year SD class for milk to obtain five joint analyses between the US and Latin America, low herd-year SD, high herd-year SD, Colombia, and Mexico. Sire and residual variances for milk were 41 and 29% smaller in Latin America than in the US, 47 and 58% smaller for low than for high herd-year SD, and 31 and 49% smaller for Colombia than for Mexico. Resultant heritabilities ranged from .20 to .29. Genetic correlations for milk yield between the US and Latin America, low and high herd-year SD, Colombia, and Mexico were .91, .82, .89, .78, and .90. Expected correlated responses for milk in Latin America, low and high herd-year SD, Colombia, and Mexico were 70, 53, 79, 56, and 78% of the direct response in the US. The scaling effects of heterogeneous variance resulted in smaller daughter milk responses in Latin America compared with the US even when herd-year SD was similar. PMID- 1880273 TI - Genetic analysis of dystocia in dairy cattle. AB - Breeding values and genetic parameters for dystocia were estimated in Normande and Holstein breeds. Dystocia scores were related to an underlying continuous variable via a threshold model. The underlying linear model included the effects of calving season, sex of calf by parity of dam, sire of calf, grandsire of calf, dam within maternal grandsire and herd-year effects. Typical results were found for the environmental effects, with a strong influence of dam parity on dystocia, a strong influence of sex of calf, and a small effect of calving season. Herd year variances were 32 and 40% of the residual variance in the Normande and Holstein breeds, respectively. Heritabilities for the Normande (Holstein) breed were .08 (.07) for direct effects and .11 (.07) for maternal effects. Correlations between sire and grandsire effects were .51 and .36 for the Normande and Holstein breeds, respectively. The corresponding correlations between direct and maternal effects were .15 and -.09. The results of this study show that a complete model for dystocia including the threshold concept and maternal effects can be applied for routine evaluation of dairy AI bulls. Maternal effects are important, and they should be considered in dystocia analysis, especially if nonrandom mating is present. Selection for reducing dystocia in calf and cow effects are not antagonistic. PMID- 1880275 TI - Additive and nonadditive genetic variance in female fertility of Holsteins. AB - Additive and nonadditive genetic variances were estimated for cow fertility of Holsteins. Measures of fertility were first lactation days open and service period as recorded and with upper bounds of 150 and 91 d, respectively. Six million inseminations from the Raleigh, North Carolina Processing Center were used to form fertility records of 379,009 cows. Data were analyzed with a model accounting for all additive, dominance, and additive by additive covariances traced through sires and maternal grandsires. Variance components were estimated by the tilde-hat approximation to REML. Heritability in the narrow sense was 2% for days open and .8% for service period. Dominance and additive by additive variance as a percentage of phenotypic variation strongly depended on imposition of upper bounds. Heritabilities in the broad sense ranged from 2.2 to 6.6% and were at least twice as large as heritabilities in the narrow sense. Effect of 25% inbreeding was only around an additional 3 d open. Specific combining abilities among bulls were estimated as sums of dominance and additive by additive interactions removing effect of inbreeding depression. Differences between maximum and minimum estimates were in the order of twice the estimated standard deviation, ranging from 1.5 to 6.7 d. Effects of inbreeding and specific combining ability could be jointly considered in mating programs following sire selection. PMID- 1880274 TI - Prepartum and peripartum reproductive performance of dairy heifers freshening at young ages. AB - Reproductive performance of five breeds (81% Holstein or Jersey) in the Florida Agricultural Experiment Station herd was evaluated from data collected over 20 yr. Data represented 1144 parturitions after gestations greater than 250 d with all twin births excluded. Number of services per conception was not affected by age at first insemination. Mean age of exposure to first service was 414 d; mean age at first parturition was 25.8 mo. Overall, 39.7% of heifers calved at 23 mo or less. Intermediate ages, 24 to 27 mo, comprised 33.9% of heifers, whereas 26.4% of heifers calved at greater than or equal to 28 mo. Overall incidences of problems at parturition were retained fetal membranes, 3.6%; dystocia, 3.8%; metritis, 10.5%; and stillbirth, 11.5%. Frequencies of stillbirth and retained fetal membranes apparently were not affected by age, but metritis increased linearly with age at first parturition. Holsteins experience higher incidences of all problems than did Jerseys. Heritability (from paternal half-sib correlation) of birth weights and gestation lengths were .31 and .24; genetic correlation was .14. Heritabilities of occurrence of stillbirth, retained fetal membranes, metritis, and dystocia were negative and considered to be 0. Heritabilities of age at first service, days from first service to conception, number of services, and age at first parturition were .22, .11, .05, and .43. Dairy producers can consider reducing age at first parturition to at least 22 mo, under environmental and management conditions of this study, without increased frequencies of problems at parturition. PMID- 1880276 TI - Inheritance of cow durability for linear type traits. AB - Final score and 14 linear type traits from appraisal by the Holstein Association were analyzed to assess inheritance of cow durability. Change of type scores from first to second parity (second minus first) was cow durability. Score for first parity, change of score from first to second parity, and FCM were simultaneously evaluated with a multiple-trait mixed model for each type trait. First analysis did not allow missing scores of cows for second parity, but subsequent analysis permitted missing data for second parity. When cows were required to have type scores for second parity, heritabilities for change of score were from zero (rear legs and foot angle) to 6% (final score). Genetic correlations of FCM and change of score were from -.35 (rump angle) to .24 (stature). When cows were not required to have type scores from second lactation, heritabilities for change of score were less than 8% for all traits except udder depth (17%). Except for dairy form and fore udder attachment, all genetic correlations of type scores from first lactation and change of score were positive. Seemingly, little new knowledge of linear type traits for ranking of sires was provided by appraisal of cows after first parity. PMID- 1880277 TI - The scanning acoustic microprobe: I. Analysis and synthesis of a spherically symmetric point spread function. AB - The scanning acoustic microprobe is a novel system which probes and characterizes, from a limited acoustic window, the fine-scale structural features of an object, point-by-point, using a multiplicity of acoustic pulses all aimed and focused at that point. Spherically symmetric, three-dimensional Gaussian pulses are synthesized to measure the backscatter diffraction pattern of the least-resolvable volume of scatterers centered at the point in question. The size and distribution of the scattering volume is forced to be constant, independent of frequency and angle. This method is analytically simple, compared with other pulse-echo techniques, and is applicable to scatterers ranging continuously in size from Rayleigh scatterers to specular reflectors. This is the first of a number of papers describing the development and application of systems based on these concepts. The analytical principles will be described herein for examination of one point at a time. In a companion paper appearing in this issue [F. E. Barber, J. Acoust. Soc. Am. 90, 11-19 (1991)], application to measurement and characterization of a discrete, flat, circular "piston" will be presented. Application to human tissue imaging and tissue characterization will be described in a subsequent third paper. The primary features detected experimentally are the strength of nondirective patterns, and the strength, orientation, and directivity of angle-dependent echo functions associated with planar or layered structures. Fine-scale structural features of a scattering center are obtained either by pattern recognition in k(data) space or inverse Fourier transformation. It is shown that when the bandwidth criteria are met to produce a spherically symmetric point spread function, scattering phenomena are completely described by only two parameters, namely the center frequency of the pulse-echo system and the characteristic diameter of the Gaussian point spread function. PMID- 1880278 TI - The scanning acoustic microprobe: II. Application to the measurement and characterization of a piston reflector. AB - In a pulsed ultrasound beam, echoes detected from a flat, circular piston of arbitrary size depend on the time-space characteristics of the entire pulse-echo measurement system, being a function of as many parameters as it takes to accurately define the system. In the limiting case of a target that is small relative to the spatial extent of an interrogating plane wave, an echo pattern is known to be a relatively simple function of the dimensionless product k0b, where k0 is the wave number and b is the radius of the target. In a companion paper preceding this one [F. E. Barber, J. Acoust. Soc. Am. 90, 8-17 (1991)], the author has described the scanning acoustic microprobe, a pulse-echo system in which the time-space properties of the interrogating waves are specified completely by k0 and a single additional parameter s0, which is the characteristic radius of a spherically symmetric, Gaussian-distributed scattering volume. In this system, the reflection pattern of a flat, circular piston of any arbitrary size is thus a function of two dimensionless parameters, namely k0b and b/s0. In this paper, this functional relationship is derived, a physical system is described, and analytical and experimental results are reported. It is shown that the diameter, orientation, and impedance mismatch properties of this simple target can be measured unambiguously over a range of target sizes from about a wavelength (2 pi/k0) to a beam diameter (about 3s0). For a typical ultrasound system, this is about a 5-1 range; i.e., a range extending to target sizes about five times smaller than can be detected in a simple B-mode imaging system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880279 TI - Anticipatory velar lowering: a coproduction account. AB - Feature spreading and coproduction models make fundamentally different assumptions about the nature and organization of speech motor control, and yet each model is supported by some, but not all, of the existing empirical data. This has led some researchers to conclude that speakers probably use alternative strategies at different times. This study suggests that the identification of coarticulatory influences requires the concurrent identification of intrinsic articulatory characteristics of the segment. Moreover, the evidence for feature spreading or variable coarticulation strategies derives from the misidentification of such intrinsic characteristics as context effects. This velar coarticulation study used a controlled comparison between CVnN and CVnC minimal pairs, where C is an oral consonant, Vn is any number of vowels, and N is a nasal consonant. Vocalic string duration was manipulated by varying the number of segments and speech rate, allowing us to alter the time between the onsets of vocalic and subsequent consonantal gestures. Velar lowering occurred in CVn sequences, whether or not a nasal consonant followed, and similar vocalic gestures were observed across minimally contrastive environments with and without the nasal consonant. Moreover, velar lowering for the nasal consonant began in close temporal proximity to the nasal murmur. These results strongly support the coproduction model and provide insight into previously conflicting reports. PMID- 1880280 TI - The effects of external- and middle-ear filtering on auditory threshold and noise induced hearing loss. AB - A model of external- and middle-ear function is described that uses existing data to quantify the flow of sound power from the environment to the cochlea of humans, cats, and chinchillas. This model estimates the sound power produced at the entrance of the cochlea by an environmental sound stimulus, and can be used to predict the shape of the auditory threshold function and the relative potency of various traumatic acoustic stimuli. The shapes of the predicted and measured threshold functions in the three species are similar in best frequency, bandwidth, and low-frequency slope, and the model accurately predicts the hypersensitivity of the middle-frequency regions of the cochlea to acoustic trauma. The model assumes that the mechanics of the middle-ear system are linear even at high stimulus levels and does not include the effects of either middle ear or cochlear efferent loops. The effects of these simplifications on the model are discussed as are the implications of the model results for hearing protection and damage risk criteria. PMID- 1880281 TI - The structural and functional consequences of acoustic injury in the cochlea and peripheral auditory system: a five year update. AB - This presentation considers important developments and new trends related to acoustic injury in the peripheral auditory system reported during the past 5 years. The discussion begins with the effect overstimulation has on the "active" cochlear process, and the associated loss in receptive field (tuning curve) selectivity. Exposure to intense sound also changes the structure and function of the tectorial membrane, sensory hair bundles, tip links, and intracellular organelles. All of these injuries may change the way in which energy is delivered to the transduction channels of the hair cell. Important new evidence describing the quantitative relation between hair cell loss and permanent hearing loss is reviewed, and the possibility that specific exposure conditions cause unique lesions to the inner or outer hair cells is explored. Finally, the importance of hair cell regeneration in the chick cochlea, changes in the CNS following acoustic injury, and the cochlear vascular system are considered. PMID- 1880282 TI - Human temporary threshold shift (TTS) and damage risk. AB - Information regarding the relation of human temporary threshold shift (TTS) to properties of steady-state and intermittent noise published since the 1966 appearance of the CHABA damage risk contours is reviewed. The review focuses on results from four investigative areas relevant to potential revision of the CHABA contours including effects of long-duration exposure and asymptotic threshold shifts (ATS); equivalent quiet and/or safe noise levels; effects of intermittency; and use of noise-induced temporary threshold shift (NITTS) to predict susceptibility to noise-induced permanent threshold shift (NIPTS). These data indicate that two of three major postulates on which the original contours were based are not valid. First, recovery from TTS is not independent of the conditions that produced the TTS as was assumed. Second, the assumption that all exposures that produce equal TTS2 are equally hazardous is not substantiated. The third postulate was that NIPTS produced by 10 years of daily exposure is approximately equal to the TTS2 produced by the same noise after an 8-h exposure. Based upon several TTS experiments showing that TTS reaches an asymptote after about 8 h of exposure, the third CHABA postulate can be reworded to state the hypothesis that ATS produced by sound of fixed level and spectrum represents an upper bound on PTS produced by that sound regardless of the exposure duration or the number of times exposed. This hypothesis has a strong, logical foundation if ATS represents a true asymptote for TTS, not a temporary plateau, and if threshold shifts do not increase after the noise exposure ceases. PMID- 1880283 TI - Recent studies of temporary threshold shift (TTS) and permanent threshold shift (PTS) in animals. AB - It is well known that excessive exposure to noise results in temporary and/or permanent changes in hearing sensitivity in both human and animal subjects. The purpose of this review is to describe the major findings from laboratory studies of experimentally induced hearing losses, both temporary and permanent, resulting from exposure to noise in animal subjects which have been published since the report of Kryter et al. (1966). The data reviewed support the following general statements: (1) The chinchilla is the most widely used and most appropriate animal model for studies of noise-induced hearing loss; (2) with continuous exposures to moderate-level noise, thresholds reach asymptotic levels (ATS) within 18-24 h; (3) permanent threshold shifts, however, depend upon the level, frequency, and the duration of exposure; (4) below a "critical level" of about 115 dB, permanent threshold shift (PTS) and cell loss are generally related to the total energy in continuous exposures; (5) periodic rest periods inserted in an exposure schedule are protective and result in less hearing loss and cochlear damage than equal energy continuous exposures; and (6) under some schedules of periodic exposure, threshold shifts increase over the first few days of exposure, then recover as much as 30 dB as the exposure continues. PMID- 1880284 TI - The role of intermittence in PTS. AB - Exposure of chinchillas to noise that is continuous results in auditory damage that is a function of the total energy of the exposure, provided that a critical exposure is not exceeded. Breaking a continuous exposure into 45 exposure periods given once a day Monday through Friday for 9 weeks (an interrupted exposure) is shown to result in a slight reduction in damage, but breaking each of the 45 daily exposures into short noise bursts presented at regular intervals (interrupted and intermittent exposures) reduces the damage more significantly. The shorter the noise bursts, the greater will be the reduction in damage. Too few data are available to establish a principle that will predict correctly the amount of reduction afforded by a particular temporal pattern; while the "equal energy" principle predicts no reduction at all, the "mean level" principle derived from studies of temporary threshold shifts (e.g., a noise at 80 dB half the time and at 100 dB half the time has a mean level of 90 dB and will have the same effect as a continuous 90-dB noise) predicts too much reduction. PMID- 1880285 TI - Field studies: industrial exposures. AB - The databases and models for the prediction of noise-induced permanent threshold shift (NIPTS) from industrial noise exposures are reviewed. Models available in 1973, compared with later models and data, are shown still to be reasonable. The effect of hearing conservation procedures on the acquisition of new data is discussed. Because of the impact of hearing conservation, new research focus is recommended in three areas: sex differences, newly hired individuals exposed for the first time in occupational noise, and the contribution of nonoccupational noise through the use of questionnaires and dosimetry. PMID- 1880286 TI - Noise exposure from leisure activities: a review. AB - Over the past two decades there has been increasing concern about the role of nonoccupational, or leisure noise on hearing. This paper reviews published studies that detail the noise levels and potential effects of some noisy leisure activities. Considered are the most common sources of leisure noise: exposure to live or amplified rock, classical, or jazz music; exposures from personal listening devices ("walkman" type); noise around the home, and hunting and target shooting. Although all activities listed above have the potential for dangerous levels of noise exposure, the most serious threat to hearing comes from recreational hunting or target shooting. PMID- 1880287 TI - Modeling the interactions between noise exposure and other variables. AB - The interaction of noise exposure with other variables is reviewed. For the case of the interaction of noise with other variables that produce behavioral threshold shifts, the application of a newly developed model is described and demonstrated. This model, referred to as the modified power-law model, provides an accurate prediction of the combined effects of two threshold-elevating factors. The model accounts for the interaction of post-exposure a pre-existing pre-existing permanent loss or a pre-existing temporary loss. The model's application is demonstrated for multiple exposures to steady-state noise in which each exposure lasts as short as 12 min or as long as 6 h. Finally, implications of the model's application to the interaction long as 6 h. Finally, implications of the model's application to the interaction of noise with other ototraumatic agents are reviewed. PMID- 1880288 TI - Impulse noise: some definitions, physical acoustics and other considerations. PMID- 1880289 TI - The energy spectrum of an impulse: its relation to hearing loss. AB - Permanent threshold shifts obtained from 242 chinchillas that were exposed to various impulse noise paradigms have been related to the energy spectra of the impulses. The impulses were generated by three different shock tubes that produced impulse noise spectra whose A-weighted energies showed peaks at 0.25, 1, and 2 kHz. The results show that there is an increasing susceptibility to NIPTS as the audiometric test frequency increases from 0.5 to 16 kHz. This increase in susceptibility to NIPTS is further accentuated by approximately 5 to 10 dB for impulses whose spectra peak at 2 kHz. PMID- 1880290 TI - Effects of peak pressure and energy of impulses. AB - Peak pressure has been one of the key parameters of impulse noise used to assess the hazard to hearing. It is used in most international noise exposure limits. France uses an A-weighted energy limit. There is a rough correspondence between peak pressure and the hazard to hearing for a given type of impulse noise. However, when the effects of different types of impulses are compared, this correspondence breaks down. One of the alternate measures of impulse intensity is weighted energy. Weighted energy is appealing for a number of reasons. It does not depend on details of the pressure-time history such as the peak pressure and the more common duration measures. It should be easier to integrate with continuous or intermittent noise standards. It would make it easier to use standard hearing protector attenuation to estimate the hazard when a specific hearing protector is worn. Results of previously published articles and reports will be discussed. These reports lead to the conclusion that weighted energy is a more potent determiner of hearing hazard than peak pressure if spectral effects are controlled. PMID- 1880291 TI - The importance of "temporal pattern" in traumatic impulse noise exposures. AB - The equal energy hypothesis (EEH) was evaluated for impulse noise. Specifically, the experiments evaluated the importance of the temporal distribution of impulses; the trading relation between the number of impulses and peak level and the difference between continuous and impulse noise. Monaural chinchillas were exposed to one of seven conditions. Their hearing was evaluated before, immediately after, and 30 days after the exposure. Hair cell damage was reported in the form of a cochleogram. The experiments show that the EEH is more appropriate for low-level impulse (135-dB peak); for equal amounts of energy, 150 dB impulses produce more hearing loss and hair cell damage than 135-dB impulses; for equal amounts of energy, impulses presented in rapid bursts cause less damage than impulses presented at "1/s" and 50 microseconds. Pairs of impulses presented at "1/s" produce the largest amount of damage. The results are discussed in terms of implications for the EEH. PMID- 1880292 TI - Insights into hazard from intense impulses from a mathematical model of the ear. AB - In order to provide insight into the mechanisms that operate in the ear when it is exposed to intense sounds, time and frequency domain mathematical models of the ear including significant nonlinearities in the middle ear were developed to trace energy flow from the free field to the inner ear and ultimately allow the calculation of basilar membrane displacement and a consequent hazard function. These models match the ear's behavior at low intensities and also reproduce many of the features of the data on hearing hazard from intense impulses. They provide critical insights into the loss mechanisms, suggest new strategies for protecting hearing as well as reducing hazard at the source and could also serve as a framework for a new, accurate, theoretically based method for rating hazard from intense sounds. PMID- 1880293 TI - The effect of pure-tone forward masking on overshoot. AB - The overshoot effect can be reduced by temporary hearing loss induced by aspirin or exposure to intense sound. The present study simulated a hearing loss at 4.0 kHz via pure-tone forward masking and examined the effect of the simulation on threshold for a 10-ms, 4.0-kHz signal presented 1 ms after the onset of a 400-ms, broadband noise masker whose spectrum level was 20 dB SPL. Masker frequency was 3.6, 4.0, or 4.2 kHz, and masker level was 80 dB SPL. Subject-dependent delays were determined such that 10 or 20 dB of masking at 4.0 kHz was produced. In general, the pure-tone forward masker did not reduce the simultaneous-masked threshold, suggesting that elevating threshold with a pure-tone forward masker does not sufficiently simulate the effect of a temporary hearing loss on overshoot. PMID- 1880294 TI - Auditory space expansion via linear filtering. AB - A signal-processing algorithm that modifies the interaural time delays associated with directional sources is described. Signals received at two microphones are processed by four linear filters arranged in a lattice configuration to produce two outputs, one for each ear. Since the processing is linear, the method is equally applicable to single or multiple directional sources. The filters are designed to minimize the average squared error between a user specified desired space warping function and the actual warping function that they implement. Two classes of filters are considered: filters whose frequency response is unconstrained and filters constrained to be causal with finite impulse response. In both cases the solution of the least-squares problem is given and properties of the actual space warping function are examined. Perceptual experiments and analysis of acoustic waveforms are utilized to demonstrate the effectiveness of the algorithm. Extension of this method for utilizing more than two microphones is described. PMID- 1880295 TI - Evaluation of orthogonal polynomial compression. AB - In orthogonal polynomial compression, the short-term speech spectrum is first approximated by a family of orthogonal polynomials. The coefficients of each polynomial, which vary over time, are then adjusted in terms of their average value and range of variation. These adjustments can be used to compress (or expand) temporal variations in the average level, slope, and various forms of curvature of the short-term speech spectrum. The analysis and reconstruction of the short-term speech spectrum using orthogonal polynomials was implemented using a digital master hearing aid. This method of compression was evaluated on eight sensorineurally hearing-impaired listeners. Speech recognition scores were obtained for a range of compression conditions and input levels with and without frequency shaping. The results showed significant advantages over conventional linear amplification when temporal variations in the average level of the short term spectrum were compressed, a result comparable to that obtained with conventional amplitude compression. A subset of the subjects showed further improvement when temporal variations in spectrum slope were compressed, but these subjects also showed similar improvements when frequency shaping was combined with level-only compression. None of the subjects showed improved speech recognition scores when variations in quadratic curvature were compressed in addition to level and slope compression. PMID- 1880296 TI - Phenomenological characterization of eardrum transduction. AB - A phenomenological description of the transduction effected by the eardrum is presented. That description is provided by a transfer matrix, whose elements define those measurements sufficient to characterize eardrum transduction. Causality provides constraints on the matrix elements. In addition, measurements of the matrix elements can determine whether they satisfy constraints imposed by minimum-phase behavior and the principle of reciprocity. Those constraints may be used either to reduce the number of measurements necessary to characterize the eardrum or to check the consistency of measurements that overdetermine the system. Within its region of validity, the transfer matrix of the eardrum provides a common ground for the comparison between theory and experiment. As an example, a simple model for the transduction characteristics of the eardrum, defined completely in terms of measurable quantities, is presented. PMID- 1880297 TI - Maturation of the traveling-wave delay in the human cochlea. AB - The maturation of the traveling-wave delay in the human cochlea was investigated in 227 subjects ranging in age from 29 weeks conceptional age to 49 years by using frequency specific auditory brain-stem responses (ABRs). The derived response technique was applied to ABRs obtained with click stimuli (presented at a fixed level equal to 60-dB sensation level in normal hearing adults) in the presence of high-pass noise masking (slope 96 dB/oct) to obtain frequency specific responses from octave-wide bands. The estimate of traveling-wave delay was obtained by taking the difference between wave I latencies from adjacent derived bands. It was found that the traveling-wave delay between the octave band with center frequency (CF) of 11.3 kHz and that with CF of 5.7 kHz decreased (about 0.4 ms on average) in exponential fashion with age to reach adult values at 3-6 months of age. This decrease was in agreement with reported data in kitten auditory-nerve fibers. The traveling-wave delays between adjacent octave bands with successive lower CF did not change with age. PMID- 1880298 TI - New approaches to nonlinear diffractive field propagation. AB - In many domains of acoustic field propagation, such as medical ultrasound imaging, lithotripsy shock treatment, and underwater sonar, a realistic calculation of beam patterns requires treatment of the effects of diffraction from finite sources. Also, the mechanisms of loss and nonlinear effects within the medium are typically nonnegligible. The combination of diffraction, attenuation, and nonlinear effects has been treated by a number of formulations and numerical techniques. A novel model that incrementally propagates the field of baffled planar sources with substeps that account for the physics of diffraction, attenuation, and nonlinearity is presented. The model accounts for the effect of refraction and reflection (but not multiple reflections) in the case of propagation through multiple, parallel layers of fluid medium. An implementation of the model for axis symmetric sources has been developed. In one substep of the implementation, a new discrete Hankel transform is used with spatial transform techniques to propagate the field over a short distance with diffraction and attenuation. In the other substep, the temporal frequency domain solution to Burgers' equation is implemented to account for the nonlinear accretion and depletion of harmonics. This approach yields a computationally efficient procedure for calculating beam patterns from a baffled planar, axially symmetric source under conditions ranging from quasilinear through shock. The model is not restricted by the usual parabolic wave approximation and the field's directionality is explicitly accounted for at each point. Useage of a harmonic limiting scheme allows the model to propagate some previously intractable high intensity nonlinear fields. Results of the model are shown to be in excellent agreement with measurements performed on the nonlinear field of an unfocused 2.25 MHz piston source, even in the near field where the established parabolic wave approximation model fails. Next, the model is used to compare the water path and in situ fields of a medical ultrasound device. Finally, the model is used to calculate the spatial heating rate associated with a nonlinear field and to simulate the phenomenon of saturation-induced beam broadening. PMID- 1880299 TI - New approaches to the linear propagation of acoustic fields. AB - New algorithms are described that provide insight into linear field propagation and offer significant reductions in computational complexity. The developments presented here include the usage of a recently developed discrete Hankel transform to implement two single step, planar propagation algorithms for baffled, radially symmetric, acoustic pressure or velocity fields; an update on the single step approaches that reduce computational complexity through geometrically determined spatial frequency limitations; and algorithms for extending to multistep propagation. Two equivalent means of introducing arbitrary medium attenuation into the above schemes are presented. Finally, a planar boundary crossing algorithm that accounts for refraction and reflection (but not multiple reflections) is added to one of the multistep propagating algorithms. The resulting algorithm is then used to examine the differences between the corresponding fields of a focused piston source operating in water and in a layered fat/liver (biomedical imaging) medium. The results yield computationally efficient algorithms that can be used for linear propagation of focused or unfocused beams in attenuating, multilayer media, and also provide the basis for a novel nonlinear propagation algorithm. PMID- 1880300 TI - Comparing human and neural network lip readers. AB - Performance in identifying nine vowels from static images of a speaker's mouth was studied experimentally for neural networks and human subjects. Data obtained indicated that they had essentially the same rate of correct identifications overall and vowel by vowel. The estimate of the probability of correct identification and 95% confidence limits were determined for each of the nine vowels. PMID- 1880301 TI - Investigations in the amplitude of sounded piano tones. AB - The relationship between final hammer velocity and maximum amplitude of radiated piano sound was investigated. Piano tones with varying hammer velocities were produced by a computer-monitored acoustic piano containing optical sensors and solenoids, and the sounded tones were recorded and digitized for analysis. Maximum amplitudes over the duration of the sounded tones were linearly proportional to piano hammer velocities for a range of frequencies and hammer velocities. Changes in room acoustics did not alter the linear relationship. Measurements of maximum amplitudes of individual tones and combined tones (dyads) also indicated a linear relationship between the sum of the maximum amplitudes of the individual tones and the maximum amplitude of the dyads. These findings indicate that the principle of superposition holds for peak amplitudes of sounded piano tones. Findings are discussed with regard to production and perception of musical dynamics. PMID- 1880302 TI - Speaker normalization of static and dynamic vowel spectral features. AB - Two methods are described for speaker normalizing vowel spectral features: one is a multivariable linear transformation of the features and the other is a polynomial warping of the frequency scale. Both normalization algorithms minimize the mean-square error between the transformed data of each speaker and vowel target values obtained from a "typical speaker." These normalization techniques were evaluated both for formants and a form of cepstral coefficients (DCTCs) as spectral parameters, for both static and dynamic features, and with and without fundamental frequency (F0) as an additional feature. The normalizations were tested with a series of automatic classification experiments for vowels. For all conditions, automatic vowel classification rates increased for speaker-normalized data compared to rates obtained for nonnormalized parameters. Typical classification rates for vowel test data for nonnormalized and normalized features respectively are as follows: static formants--69%/79%; formant trajectories--76%/84%; static DCTCs 75%/84%; DCTC trajectories--84%/91%. The linear transformation methods increased the classification rates slightly more than the polynomial frequency warping. The addition of F0 improved the automatic recognition results for nonnormalized vowel spectral features as much as 5.8%. However, the addition of F0 to speaker-normalized spectral features resulted in much smaller increases in automatic recognition rates. PMID- 1880303 TI - Effects of first formant onset properties on voicing judgments result from processes not specific to humans. AB - Both first formant (F1) transition duration and F1 onset frequency have been proposed to be perceptually significant in categorization of voiced and voiceless syllable-initial stops. Transition duration per se may not, however, explain the fact that, for longer transitions, longer F1 cutback is required in order to perceive a stop as voiceless. Longer transitions result in lower F1 onsets at any duration of cutback greater than zero, and it is possible that the major effect of F1 is determined by its frequency at onset. In this study, F1-transition duration, onset frequency, and slope were varied across four types of F1 transition in which one of the three variables (onset frequency, duration, slope) was held constant while the other two were allowed to vary. Each of the four F1 types was used in syllables with higher formants appropriate for labial, alveolar, and velar places of articulation. By far, the best predictor of identification of these stimuli by human listeners was F1 onset frequency. F1 duration, F1 slope, and place of articulation had little or no effect on labeling boundaries. In a second experiment using Japanese quail (Coturnix coturnix japonica), birds were trained to respond differentially to voiced versus voiceless stops. The differential effects of F1 onset frequency on the "labeling" behavior of these birds was strikingly similar to that of humans listening to the same stimuli. These results are taken to provide strong evidence that F1 onset frequency is the primary determinant of shifts in voicing boundaries across place of articulation, and that general mechanisms not unique to humans appear adequate to account for the effects of F1 onset frequency on perception of voicing for syllable-initial stops. PMID- 1880304 TI - Suicide and panic disorder: a review. AB - This article reviews the risk of suicide in panic disorder beginning with early studies showing increased mortality, including suicide, among patients belonging to the broad category of neuroses. More recent follow-up studies of patients with anxiety disorders have found about 20% of deaths due to suicide, a proportion similar to that found in depressive disorders. Also, suicide attempts have been reported by similar proportions of subjects with panic disorder and major depression from the general population. Preliminary data indicate that more severely ill patients with coexisting depression and substance abuse are more likely to attempt or complete suicide. Thus, although limited, the data indicate that the risk of suicide in panic disorder is substantial. As a consequence, clinicians should alert themselves to this preventable outcome and approach treatment with added caution. PMID- 1880305 TI - The Hamilton Depression Rating Scale (HDRS); changes in scores as a function of training and version used. AB - The co-existence of different versions of the Hamilton Depression Rating Scale (HDRS) may introduce a source of error in depression research. In a training procedure, based on 16 videotapes, over 900 scores were used to investigate differences between two prominent versions. The HDRS published by Bech et al. in 1986 produced significantly lower total scores than the original HDRS presented by Hamilton in 1960. Previous experience of the raters, both in psychiatry and in the use of the scale, increased the scores in a nonsignificant way. During the training raters' scores increased significantly. These effects were small, one point each in the total scores, but they were consistent throughout our material. In depression research, training procedures and the exact version of the scales used should be specified. PMID- 1880306 TI - Organic mood disorder: a valid psychiatry consultation diagnosis? AB - To determine the validity of the DSM-IIIR category organic mood disorder, we compared 50 psychiatric consultations with this diagnosis to 50 psychiatric consultations diagnosed with major depression in the medically ill. Organic mood disorder patients were more likely to be in the index affective disorder episode and have a negative family history of depression. Despite similar pharmacologic treatment between groups, the organic mood disorder group was less likely to be completely recovered at 4 years follow-up. This study suggests organic mood disorder is a valid diagnosis in the psychiatry consultation service. PMID- 1880307 TI - Imipramine an effective treatment for illness phobia. AB - Ten subjects with illness phobia were treated with imipramine for 8 weeks. All of the eight subjects who remained on the drug for 4 weeks or more reported at least moderate improvement. Overstimulatory reactions occurred in four subjects causing two to discontinue medication. Imipramine appears to be a potentially useful treatment for this subtype of hypochondriasis. PMID- 1880308 TI - Menstrual cycle phase and psychiatric admissions. AB - Several surveys have demonstrated increased psychiatric admissions during the para-menstrual phases of the menstrual cycle (4-5 days before and during the onset of menses). We assessed menstrual cycle phase in 51 carefully diagnosed women at the time of emergency psychiatric admission and contrasted their cycle phase distribution with 113 normal hospital staff members assessed at random upon arrival at work. Consistent with other studies, 47% of psychiatric admissions occurred during the para-menstrual phase in contrast to 22% of staff controls (chi 2 = 9.27; df = 1; P = 0.002). Within the group of psychiatric patients, 33.3% of admissions occurred within 4 days of the onset of menses (chi 2 = 12.45; df = 6; P = 0.052). There were no significant phase differences found between major depressive and schizophrenic patients, between acutely suicidal and non suicidal patients, and no significant correlation was noted with depression rating scales. Thus, it appears that menstrual cycle entrainment and associated late luteal phase biological changes may have additive effects which are sufficient to exacerbate the expression of psychiatric disorder in vulnerable patients, independent of their diagnosis. PMID- 1880309 TI - Measuring the severity of depression through a self-report inventory. A comparison of logistic, factorial and implicit models. AB - The present study investigates the psychometric adequacy of a self-report inventory of depression (the QD2) with respect to the severity of depressive symptoms, within the framework of a unidimensional model of depressive states. Responses to the 52 QD2 items, by 481 subjects divided into four groups (depressed, psychiatric, somatic and control), were subjected to a Rasch analysis. Results show that 15 items (QSD(R1] display a satisfactory goodness of fit for both items and persons, as defined by the Rasch model. This set of items, solely related to 'pure' depression, gives a measure of the severity of depression, free from anxiety symptoms. The discussion focuses upon the advantages of the Rasch model as compared to traditional tests. The Rasch 15-item solution should provide a parsimonious tool for future studies on the classification of depressive disorders. PMID- 1880310 TI - Validation of a computerised version of the 10-item (self-rating) Edinburgh Postnatal Depression Scale. AB - Twenty-nine women were obtained from two community-based facilities and administered the 10-item Edinburgh Postnatal Depression Scale (EDPS) in a computerised and 'pencil and paper' form. A high correlation (r = 0.98) was found between the two test types. The computerised test was found to be acceptable to all women in the study. Our findings suggest that the computerised form of the EPDS may be of use in screening women in community settings and may also be valuable in antenatal or postnatal clinics. PMID- 1880311 TI - Major depression in panic disorder: role of recent life events. AB - The authors assessed life events during the year before the onset of panic disorder in 57 panic patients with a lifetime history of major depression. Compared with a group of 43 panic patients without major depression, the group with depression had experienced more severe events. The clinical and theoretical implications of these results are discussed in the context of current concepts regarding the role of recent life events in comorbidity of panic disorder and major depression. PMID- 1880312 TI - Phenomenological comparisons of major depression following stroke, myocardial infarction or spinal cord lesions. AB - Patients with major depression admitted to hospital with acute stroke (n = 44), acute myocardial infarction (n = 25), or acute spinal cord injury (n = 12) were examined for differences in their phenomenological presentation of major depression. Depressed stroke patients were found to have significantly higher scores on the syndrome clusters for generalized anxiety and ideas of reference than depressed cardiac or spinal cord injury patients. In addition, significantly more stroke patients met diagnostic criteria for generalized anxiety disorder compared with the other two groups. Although spinal cord injury patients were younger, more likely to be treated with benzodiazepines, and less likely to be treated with beta-blockers, none of these factors distinguished stroke patients with anxious depression from stroke patients with depression only. These findings are consistent with the hypothesis that the etiology of depression following stroke may be different from that associated with myocardial infarction or spinal cord injury. PMID- 1880313 TI - EEG sleep of young adults with major depression: a controlled study. AB - The EEG sleep of 75 subjects aged 16-25 years was studied. Thirty-eight were in an episode of RDC major depression, and 37 were normal controls. Only one sleep continuity measure differed between the two groups: sleep latency was significantly longer in the depressive group. REM period latencies and other sleep variables did not differ between the groups. Subgroup analyses, within the depressed group with respect to inpatient status, revealed significantly higher REM density (P less than 0.03) and a marginally shortened REM period latency (P less than 0.07) among the inpatient depressives. Subgroup analysis across suicidal ratings revealed a significantly higher REM density (P less than 0.04) among suicidal depressives. Severity estimates of depression did not correlate with sleep findings. These results parallel another recent report on adolescent depressed subjects, suggesting that inpatient and/or suicidal status is an important variable in the expression of EEG sleep abnormalities in the adolescent/young adult age group. PMID- 1880314 TI - Sheldon Memorial Lecture. Medical management of nasal polyps and sinusitis. PMID- 1880315 TI - Glucocorticoid therapy for asthma: clinical pharmacology. PMID- 1880316 TI - Use of streptokinase as a recall antigen for lymphocyte proliferation testing in vitro. AB - The use of streptokinase (SK) as a recall antigen (Ag) for stimulation of human lymphocyte proliferation in vitro was evaluated. SK is a potent stimulant, inducing a greater response than three other Ags, tetanus toxoid, Candida albicans extract, or streptolysin. The optimum stimulatory concentration is 1000 U/ml, and peak stimulation occurs between days 6 and 8. Human cord-blood lymphocytes do not respond to SK, suggesting that it is an Ag and not a mitogen. The response rate in an adult population was 82%, higher than the rate of two other Ags tested (tetanus toxoid or Candida). These findings demonstrate the ability of SK to act as a potent recall Ag for human lymphocyte proliferation in vitro. PMID- 1880317 TI - Identification of a major peanut allergen, Ara h I, in patients with atopic dermatitis and positive peanut challenges. AB - Peanuts are among the most common causes of immediate hypersensitivity reactions to foods. Serum from nine patients with atopic dermatitis and a positive double blind, placebo-controlled, food challenge to peanut were used to begin the process of identification and purification of the major peanut allergens. Identification of a major peanut allergen was accomplished by use of anion exchange column chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, ELISA, thin-layer isoelectric focusing, and IgE-specific immunoblotting. Anion-exchange chromatography revealed several fractions that bound IgE from the serum of the challenge-positive patient pool. By measuring antipeanut-specific IgE in the ELISA and in IgE-specific immunoblotting, we identified an allergenic component with two Coomassie brilliant blue staining bands by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a mean molecular weight of 63.5 kd. Examination of this fraction by the IgE antipeanut ELISA with individual serum and by the ELISA-inhibition assay with pooled serum, we identified this fraction as a major allergen. Thin-layer isoelectric focusing and immunoblotting of this 63.5 kd fraction revealed it to have an isoelectric point of 4.55. Based on allergen nomenclature of the IUIS Subcommittee for Allergen Nomenclature, this allergen is designated, Ara h I (Arachis hypogaea). PMID- 1880318 TI - Effect of low-dose methotrexate on the disposition of glucocorticoids and theophylline. AB - Low-dose methotrexate (MTX) therapy has been recently proposed as alternative therapy for patients with severe steroid-requiring asthma. Several questions have been raised regarding the mechanism of action, including alteration of pharmacokinetics of two medications used in these patients, specifically, glucocorticoids and theophylline. To address this question, pharmacokinetic studies were performed at baseline and after 6 weeks of treatment with either intramuscular MTX or placebo (folic acid). Plasma concentrations of theophylline were measured by fluorescence polarization immunoassay (TDx, Abbott Diagnostics, Abbott Park, Ill.). Prednisolone, methylprednisolone, and cortisol concentrations were measured by high-performance liquid chromatography. Fifteen adults were enrolled in the double-blind, placebo-controlled trial. No change in prednisolone pharmacokinetic parameters was found. Theophylline clearance decreased an average of 19% in patients randomized to receive MTX, from 48.0 +/- 2.0 ml/hr/kg to 38.9 +/- 3.6 ml/hr/kg (p less than 0.05). This change resembles change observed with theophylline and phenobarbital clearance in which a high degree of interpatient variability is observed. The most likely explanation for the change in theophylline clearance is inhibition of hepatic microsomal enzyme activity. Three patients complained of adverse effects, and dosage was reduced in one patient. The variable effect of MTX on theophylline clearance indicates that theophylline concentration monitoring should be performed in patients receiving both drugs. PMID- 1880319 TI - Comparison of platelet-activating factor-induced chemotaxis of normodense and hypodense eosinophils. AB - Platelet-activating factor (PAF)-induced eosinophil (EOS) migration is an important event in the development of tissue eosinophilia and allergic inflammation. EOSs are heterogeneous cells in that different states of activation have been ascribed to EOSs of varying densities. We therefore studied the ability of PAF to induce hypodense and normodense EOS chemotaxis. Both hypodense and normodense EOSs were isolated in pure form from seven subjects and studied concurrently. Dose-response and time-course experiments indicated no significant differences in PAF-induced hypodense versus normodense EOS chemotactic responses. Hypodense and normodense cells achieved maximal chemotaxis in response to 1 mumol/L of PAF, and maximal chemotaxis was achieved at 2 hours. However, marked differences in PAF-induced EOS chemotactic responses existed between patients. We conclude that PAF is a potent EOS chemoattractant, and despite reported differences in metabolic activity, normodense and hypodense EOSs exhibit similar chemotactic responsiveness to PAF. PMID- 1880320 TI - Bee venom anti-idiotypic antibody is associated with protection in beekeepers and bee sting-sensitive patients receiving immunotherapy against allergic reactions. AB - Bee venom (BV) anti-idiotypic (anti-Id) antibodies (Abs) were studied in nonreactive beekeepers, patients receiving BV immunotherapy (IT), and in patients with bee-sting hypersensitivity. Detection of serum anti-BV was determined either by the Phadebas RAST test for IgE and IgG concentrations or by isoelectric focusing followed by capillary blotting onto nitrocellulose membranes. Clonotypic analyses of Ab were made with specific probes for BV or BV anti-Id; 13/14 nonreactive multiple-sting beekeepers (93%; p = 0.00006) and 3/3 patients receiving BV IT (100%; p = 0.0026) had detectable amounts of BV anti-Id in serum, whereas five BV-sensitive patients (0%) and four ragweed-sensitive control patients (0%) did not. Beekeeper's serum containing BV anti-Id was found to recognize and bind to IgE anti-BV idiotype from two different patient sources and inhibit their reactions in a Phadebas RAST test in a dose-dependent manner. Nonreactive beekeepers generally had BV-specific IgE levels less than 0.35 PRU/ml in serum with detectable BV anti-Id. BV-allergic patients before IT had elevated BV-specific serum IgE levels, even in the presence of BV-specific IgG greater than 136 U/ml with no BV anti-Id present. These findings provide strong support for a protective role of BV anti-Id against bee sting--allergic reactions. PMID- 1880321 TI - Methotrexate in the treatment of steroid-dependent asthma. AB - A double-blind, placebo-controlled, crossover study was designed to compare steroid requirements between placebo and methotrexate (MTX) treatment in subjects with corticosteroid-requiring asthma. Subjects began with a steroid taper and then were randomized to a 3-month trial of drug or placebo therapy. Subjects received 15 mg of MTX a week or identical placebo. A 1-month washout period was completed before the crossover trial. Symptom scores, peak flow rates, spirometry, and beta-agonist frequency were closely monitored. Ten subjects completed the study. The average dose of prednisone during the placebo-treatment period was 11.97 mg/day compared to 8.37 mg/day while subjects were taking MTX. This was a 30% reduction in daily steroid requirement (p less than 0.01). Symptom scores and spirometry did not differ between the crossover trials, and overall clinical status was not altered. Complications from MTX were mild and included anorexia, alopecia, and stomatitis. All complications resolved with dose reduction or when MTX was stopped at the end of the study. No subjects withdrew from the study because of MTX complications. Low-dose MTX significantly reduced the steroid requirement in this group of subjects with steroid-dependent asthma. This reduction in steroid requirement was obtained without altering clinical status and without significant complication. PMID- 1880322 TI - Penicillin resensitization among hospitalized patients. AB - The purpose of this study was to determine the frequency of resensitization to penicillin after oral or intravenous treatment with beta-lactam antibiotics in hospitalized patients with histories of penicillin allergy. Seventeen adults (aged 24 to 76 years) and one child (aged 10 years) were treated intravenously and/or orally with beta-lactam antibiotics after negative skin tests were obtained with benzylpenicilloyl polylysine, potassium penicillin G, and alkaline hydrolysis products of penicillin G as minor determinant mixture. Repeat skin testing was performed 1 to 12 months after the therapy. Three patients (16%) became skin test positive after the treatment. Two patients reacted to potassium penicillin G alone, and the other patient reacted to benzylpenicilloyl polylysine and minor determinant mixture. These three patients were among the 15 patients who were treated with intravenous antibiotics. This study reveals a high percentage of skin test conversion after intravenously administered penicillin therapy and confirms the present practice of advising patients with a history of penicillin allergy who have successfully completed penicillin treatment to have a repeat skin test before future exposure to beta-lactam antibiotics. PMID- 1880323 TI - Identification of the major activity derived from cultured human peripheral blood mononuclear cells, which enhances eosinophil viability, as granulocyte macrophage colony-stimulating factor (GM-CSF). AB - Eosinophils (EOSs) cultured in the presence of 50% peripheral blood mononuclear cell (PBMC)-derived culture supernatants remained 67% +/- 7% (mean +/- SEM; n = 5) viable for 7 days. In the absence of PBMC supernatant, only 15% +/- 7% of cells remained viable for 7 days. PBMC supernatants from six atopic individuals, with eosinophilia, and six normal subjects, with no eosinophilia, were compared for EOS viability-enhancing activity with the same target EOSs. Optimal conditions for the production of viability-enhancing activity by mononuclear cells were established as a 24-hour culture period, with a concentration of 2 x 10(6) cells per milliliter. Comparison of monocyte-enriched and lymphocyte enriched culture supernatants for the production of the EOS viability-enhancing activity indicated that both cell types released the factor. C-18 Sep-Pak separation of the PBMC culture supernatant yielded a major EOS viability enhancing activity in the aqueous eluent, suggesting a hydrophilic molecule. This major activity was neutralized by a specific antibody to granulocyte/macrophage colony-stimulating factor but was unaffected by specific antibodies to interleukin-3 and interleukin-5. A second, minor viability-enhancing activity was observed in the 100% methanol fraction, indicating the presence of a more hydrophobic molecule. The supernatants from the PBMCs of the atopic individuals consistently enhanced EOS survival to a greater extent than supernatants from the PBMCs of the normal, nonatopic individuals. PMID- 1880324 TI - An ELISA spot assay for quantitation of human immunoglobulin-secreting cells. AB - The elucidation of changes in populations of immunoglobulin-secreting cells has been a cumbersome process. We present a simplified method for the enumeration of human immunoglobulin-secreting cells with an ELISA spot assay (ESA). This method is specific, will detect all isotypes, including IgE, and is sensitive, detecting as little as 10 pg of antibody secreted. In this article, we describe the methodology for performing the ESA, demonstrate the kinetics for optimal use in both B-lymphoblastoid lines and fresh B cells, and determine the correlation between the ESA and immunoglobulin secretion under various experimental conditions. This assay permits an estimate of the level of immunoglobulin secreted per cell, thus distinguishing expansion of immunoglobulin-secreting cell populations from increases in average (per cell) immunoglobulin production. The combination of ESA and quantitation of immunoglobulin in supernatants of cultured cells provides an easy and reliable means for studying the regulation of immunoglobulin secretion. PMID- 1880325 TI - Intranasal fluocortin butyl in patients with perennial rhinitis: a 12-month efficacy and safety study including nasal biopsy. AB - Fluocortin butyl (FCB) is a recently developed topical intranasal corticosteroid that is inhaled as a powder and has been demonstrated to be well tolerated and to improve symptoms and signs of perennial rhinitis in previous short-term studies. This multicenter, open-label study evaluated the efficacy and safety of FCB during a 12-month treatment period in patients with perennial rhinitis. Treatment was initiated with one inhalation of FCB in each nostril three times a day (total dosage, 3 mg/day). In subsequent months, one third of the patients was maintained at the dosage of 3 mg/day, one third at a lower dosage of 2 mg/day, and the remaining one third of the patients at a larger dosage of 4 to 8 mg/day. Of 109 patients enrolled in the study, 90 patients (82.6%) completed all 12 months of treatment. Symptom and sign scores decreased significantly (p less than 0.001) at the 2-month evaluation compared to scores at baseline, and the improvement was maintained throughout the 12-month study period. After 12 months, greater than 80% of the patients had substantial control of symptoms. Specimens of nasal biopsies, performed at the beginning and end of treatment, revealed a decrease in eosinophils and other cellular infiltrates, a slight tendency of an increase in mast cell counts, and a trend toward normalization of the nasal mucosa. There were few adverse effects. Mean plasma cortisol levels were normal before and after corticotropin stimulation at baseline and after 12 months of FCB therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880326 TI - Newly generated IgE antibodies to Dermatophagoides pteronyssinus in children are directed against components distinct from Der p I and Der p II. AB - The specificity of newly generated IgE antibodies (Abs) to the house dust mite, Dermatophagoides pteronyssinus, in longitudinal serum samples from 18 young children with an increased risk for IgE-mediated allergy was studied. The first IgE Ab response to house dust mite was detected early in life (mean age, 32 months; range, 11 to 60 months). For 83% of the children, more than half of the newly generated IgE Ab response to house dust mite was directed against components distinct from the major allergens, Der p I (Pl) and Der p II (DpX). These results suggest that the early IgE Ab response to house dust mite is induced by components distinct from the major allergens, Der p I and Der p II. PMID- 1880327 TI - Methotrexate and asthma. PMID- 1880328 TI - Abnormal liver-function tests associated with long-term systemic corticosteroid use in subjects with asthma. PMID- 1880329 TI - Metronidazole hypersensitivity and oral desensitization. PMID- 1880330 TI - In re: Letter by Kerrebijn in JACI. PMID- 1880331 TI - Clinical trial with ketotifen. PMID- 1880332 TI - In re: Van Bever HP, Stevens WJ. (JACI 1990;86: 141-6) PMID- 1880333 TI - The prevention of adsorption of interferents to radiolabelled protein by Tween 20. AB - Radiolabels are often used to quantitatively determine the amount of protein immobilized on chromatographic supports, immunochemical plates and biosensor surfaces. Bovine serum albumin (BSA) was chosen as a model protein for quantitative deposition studies. BSA was radioiodinated (125I-) or fluorescently labelled (fluorescein), then incubated with the following surfaces: quartz, quartz derivatized by 3-aminopropyltriethoxysilane (Qz-APTES), and Qz-APTES reacted with glutaraldehyde or tresyl chloride. The amounts of BSA immobilized to the different surfaces were compared using data from radioactivity and fluorescence assays. Irreproducible results were obtained with radioiodinated BSA due to adsorption/desorption behaviour of an unidentified radioactive species. When the non-ionic detergent Tween 20 was added to the protein/surface incubation mixture, radiolabelled BSA gave reproducible protein binding results which agreed with fluorescent protein binding patterns. The effect of Tween 20 was due to either the binding to BSA displacing the interferent and/or the solubilization of the interferent. PMID- 1880334 TI - Detection of FGF-beta mRNA in chondrosarcoma cells by a new in situ hybridization technique with synthetic oligonucleotide probes. AB - Fibroblast growth factor beta (FGF-beta) is a potent mitogenic and angiogenic factor produced by a large number of normal and transformed cells. In this paper we report a new application of the in situ hybridization procedure which has allowed the detection of FGF-beta mRNA in chondrosarcoma cells using 35S-labelled synthetic oligonucleotide probes. PMID- 1880335 TI - High-performance liquid chromatography of proteins on deformed nonporous agarose beads: immuno-affinity chromatography, exemplified with human growth hormone as ligand and a combination of ethylene glycol and salt for desorption of the antibodies. AB - An affinity chromatography column packed with nonporous agarose beads derivatized with human growth hormone via carbonyldiimidazol was used for the purification of antibodies against human growth hormone from antiserum. Desorption with 1 M sodium chloride in 60% ethylene glycol at pH 9.8 gave 100% total recovery of the antibodies, as measured by radioimmunoassay. The adsorption/desorption process is discussed in terms of hydrophobic and electrostatic interaction (these interactions may be involved in the bond between antibody and antigen in a cooperative fashion). The binding capacity of the column was estimated at about 50 micrograms of antibodies per gram sedimented agarose beads. PMID- 1880336 TI - Effect of dimethyl sulphoxide and some antibiotics on cultured human T-lymphoma cells as measured by microcalorimetry. AB - The influence of dimethyl sulphoxide (I), penicillin/streptomycin (II), gentamicin (III), and amphotericin B (IV) on growing human T-lymphoma cells was measured by microcalorimetry. There was a dose-dependent decrease in the heat production rate of the cells after 24 h of incubation with I in concentrations ranging from 0-2% (v/v). At 3.6%, about half of the cells died. II and III had no effect on the cells after incubation for 6 days, at concentrations from 1 to 10 times that of the normal (50-500 IU/ml; 50-500 micrograms/ml). IV was used in combination with II (50 IU/ml; 50 micrograms/ml) and III (50 micrograms/ml), respectively, at concentrations between 0.25 and 7.5 micrograms/ml. After 6 days of incubation, the results were similar to those obtained with II and III separately. PMID- 1880337 TI - [Moebius syndrome. Apropos of 2 cases]. AB - Moebius syndrome is unusual and associates facial diplegia with a failure of lateral movements, and seems to be of nuclear or supranuclear origin, appearing during foetal life. Association with somatic malformations are frequent such as those of Poland syndrome. Surgery's envisaged when palsy of lateral movements is associated with deviation of the eyes. PMID- 1880338 TI - [Allergic granulomatous nodule of the conjunctiva disclosing onchocerciasis]. AB - A new case of conjunctival allergic nodule is reported in a Guinean man. This lesion was first described by Ashton and Cook in 1979. Histologically, this nodule consists of amorphous eosinophilic material surrounded by epithelioid and giant cells arranged in a pallisade; some eosinophils are often found in the inflammatory reaction. This lesion usually resolves spontaneously. In documented cases, nematodes and particularly filaria such as Mansonella perstans are usually isolated. Our observation is the first documented case with Onchocerca volvulus. Microfilariae were detected by examination of normal saline containing the biopsy specimen. The new major antifilarial treatment ivermectin was associated. PMID- 1880339 TI - [Embolic retinitis in Haemophilus parainfluenzae endocarditis]. AB - Infectious embolic retinopathy occurring secondary to a bacterial endocarditis is described in a 38-year-old woman with known aortic disease. The infectious organism was a haemophilus parainfluenzae confirmed by serial blood cultures and characterized by an embolic power equal to fungal infection. After four-weeks period of appropriate and intensive antibiotic therapy, blood cultures became negative but new emboli were observed in the fundus. This report describes ocular lesions rarely observed in endogenous bacterial retinitis. The delay between the bacterial endocarditis and the occurrence of the retinitis emphasizes the need for a long-term follow-up. Ophthalmologic examination can be acline for changing the heart valve. PMID- 1880341 TI - [Organotypic culture of human corneal epithelium. Preliminary results]. AB - The authors compared the growth of limbal and central explants removed from human cornea. Epithelial growth began on the third day, was greater during the first week and was subsequently slightly invaded by fibroblasts. This study demonstrated that peripheral corneal epithelial cells growth better than central cells. In this study, the cytologic and histologic features of the cells were examined. However, epithelial immunofluorescence staining by anti-cytokeratin antibodies was rather poor. This in vitro system may provide a suitable model for epithelial human corneal cell culture, allowing further biocompatibility studies. PMID- 1880340 TI - [Familial form of gelatin drop corneal dystrophy]. AB - We report 4 cases of gelatin drop dystrophy corneal amyloidosis in two brothers and two sisters of the same family. The age of onset is between 1 and 10 years. The corneal signs are described at different stages of development. Lesions are initially asymmetrical. The typical is a subepithelial nodule starting in the center and then expanding to involve the whole cornea. There is no relationship between extension and outcome of the disease. Diagnostic is confirmed by histological examination. There was no consanguinity between parents and no other cases were found in the family. An immunological study with HLA typing was performed. All patients were treated with lamellar or transfixing keratoplasty with a follow-up of 2 to 5 years. PMID- 1880342 TI - [Peripheral vitelliform lesions in vitelliform macular dystrophy]. AB - We report an unusual case of vitelliform macular dystrophy due to the presence of bilateral peripheral vitelliform lesions. Multiple forms involving posterior pole only and peripheral non specific lesions have already been described but this is the first case published, to our knowledge, showing typical vitelliform lesions in the periphery. These lesions developed in the same way as macular lesions, but they were complicated by a schisis in the left eye. In addition to other electrical and histopathological evidence, this case provides clinical evidence of the diffuse involvement of the retinal pigment epithelium in this disease. This involvement is linked to the accumulation of lipofuscin and granular substance, produced by photoreceptors. The macular predominance of vitelliform lesions can be partly explained by the metabolic and vascular particularities of the macula, but a genetic factor may be involved in the topographic determination of lesions. The development of a schisis on the edge of one of the described lesions encourages systematic search of peripheral lesions in cases of vitelliform macular dystrophy. PMID- 1880343 TI - [Posterior fixation keratoprosthesis]. AB - Keratoprosthesis is the last solution available to the corneal blind patient unsuitable for corneal graft. Keratoprosthesis by anterior fixation requires repeated operations and results are therefore variable. The concept of keratoprosthesis by posterior fixation is presented. This theoretically reduces the risk of expulsion. Only one operation is required and this reduces complications. Initial results, described here, are encouraging. PMID- 1880344 TI - [Influence of topical administration of diclofenac on the reduction of intraocular pressure induced by timolol in healthy subjects]. AB - The presence or absence of an interaction between topical diclofenac (nonsteroidal antiinflammatory agent) and topical timolol (beta-blocker) was studied in 37 eyes. We instilled one drop of diclofenac several times into the patient's right eye and one drop of timolol into the same eye. We measured intraocular pressure in both eyes twice and compared the results in both eyes with the baseline intraocular pressure and with the pressure after administration of diclofenac alone and timolol alone. The joint use of both drugs did not modify the decrease in the ocular pressure induced by timolol. We can therefore use timolol and diclofenac together when a combination of antiinflammatory and beta blocker agents is required. PMID- 1880345 TI - [Surgical treatment of primary and secondary cataract in severe myopia]. AB - Secondary cataract after extracapsular surgery is one of the main complications in aphakic eyes. In severely myopic eyes secondary cataract not only impairs visual acuity but also interferes with peripheral retinal exploration; in these eyes Nd-Yag laser capsulotomies are not recommended because of the high risk of retinal detachment and also because this technique does not solve problems related to peripheral retinal examination. For these reasons, in severely myopic eyes the authors perform extra capsular cataract extraction without IOL implantation and, if secondary cataract appears, they perform surgical cleaning of the capsule. The authors emphasise the good visualization of the peripheral retina obtained with this technique. PMID- 1880346 TI - [Value of very low voltage halogen lighting of desaturated panel D 15 test in established glaucoma]. AB - The colour vision of a first group of glaucomatous patients was tested with the desaturated Panel D 15 test, first illuminated by a 300 lux Macbeth lamp, then with a very low voltage 1000 lux halogen lamp. In addition to the recording of 80% cases of dyschromatopsia, in line with previously published data, we demonstrated a great number (33.3%) of red-green axis anomalies under Macbeth light and, paradoxically, even more under halogen light (53.3%). To explain this high percentage of red-green axes under halogen light, we discuss the influence of luminance and emission spectrum of the light source. We conclude that the use of high luminance halogen light is capable of revealing concealed Verriest type II dyschromatopsias probably due to a specific fragilisation of the red-green channels induced by the glaucoma disease. This original colour vision testing procedure applied on established glaucomatous patients enabled us to easily obtain a factor of severity in the course of the disease. PMID- 1880347 TI - Iatrogenesis in the elderly. Drug-related problems. AB - Drug reactions are generally related to the influence of age, toxicity, side effects, immunologic reactions, idiosyncratic reactions, drug-drug interactions, and drug-disease interactions. In addition to age-related changes, the elderly are susceptible to the incidence of adverse drug reactions because of polypharmacy, incorrect self-administration of drugs, omission of drugs, taking another's prescriptions, use of over-the-counter drugs, and medication errors by health-care personnel. To prevent or predict adverse drug reactions, the gerontologic nurse can obtain thorough drug histories, educate clients and health care providers, use nursing measures to alleviate symptoms, and be astute for the potential for problems through drug review. PMID- 1880348 TI - Iatrogenesis in the elderly. Contributors to falls. AB - Persons who are susceptible to falls can be identified before a fall occurs. A risk prediction tool must be evaluated for its usefulness; if a tool is not feasible, elderly persons who have fallen once are at high risk of falling again. Once high risk has been identified, strategies must be planned to prevent subsequent falls. One of the most important strategies is to communicate to all staff which patients are at high risk and the general circumstances surrounding any patient fall. Few interventions have been shown through rigorous clinical studies to be effective. Passive interventions, such as alarms, are usually more reliable than active interventions that staff must administer. Interventions must be individualized, based on the patient's deficits. PMID- 1880349 TI - Iatrogenesis in the elderly. Impaired skin integrity. AB - Risk factors that contribute to pressure ulcer formation include immobility and inactivity, age, malnutrition, fecal and urinary incontinence, and a decreased level of consciousness. Gerontological nurses should collaborate with other health disciplines (eg, the physician, physical therapist, and dietitian) to plan and provide preventive treatment measures for the elderly person with potential for impaired skin integrity: pressure ulcers. Gerontological nurses must continue the development and refinement of tools with which to predict the degree of risk for impaired skin integrity, as well as use a consistent method of grading pressure ulcers. PMID- 1880350 TI - Iatrogenesis in the elderly. Nosocomial infections. AB - The elderly are increasingly susceptible to nosocomial infection because of age related changes and the presence of multiple chronic illness. Epidemics frequently occur in long-term care facilities with upper respiratory infections, diarrhea, conjunctivitis, and antibiotic-resistant bacteria the most common. Other common nosocomial infections are those of the respiratory tract, gastrointestinal tract, genitourinary system, and integumentary system. Infection control programs, systematic surveillance, regular inservice programs on infection control (especially handwashing), and employee and resident health programs can be instituted to decrease the incidence of nosocomial infections. PMID- 1880351 TI - Nursing foot care for the aged. PMID- 1880352 TI - Iatrogenesis in the elderly. Factors of immobility. AB - Mobility of elderly patients is a consequence of the interaction between factors including biological health, sensory-perceptual capacity, motor skills, cognitive capacity, and ego-strength; and environmental resources including physical and architectural features, medical regimens, institutional policies, resident and staff characteristics, and social support availability. Impaired mobility, whether self- or other-imposed, places the elderly at risk for a multitude of negative physiological and psychological consequences that can affect health, well-being, and quality of life. Understanding the basic mechanisms underlying the physiological and psychological consequences of immobility, the relative time frame in which they can develop, and the concomitant changes associated with aging provides the basis for interventions aimed at preventing or minimizing them. A multitude of factors that influence the elderly's state of mobility are within nursing's realm of practice. Although elderly patients may present a special challenge, the negative consequences of immobility can be avoided, to a significant extent, with astute and vigilant nursing management. PMID- 1880354 TI - Further experience with the bipedicled neurovascular island flap in thumb reconstruction. AB - A procedure is described for the transfer of sensibility to the thumb by means of an island flap. The donor site is the dorsoradial surface of the index finger. The flap is supplied by two neurovascular pedicles. The palmar one includes the digital artery of the index and the dorsal branch of the palmar digital nerve. The dorsal pedicle includes the dorsoradial artery and nerve of the index and one or two superficial veins. This procedure was used in 29 patients without early postoperative complications. The advantages of the method are the resurfacing of the prehensile surface of the thumb by a flap with good arterial and venous supply while preserving the innervation and the palmar skin of the donor finger. PMID- 1880353 TI - Severe complex injuries to the upper extremity: revascularization and replantation. AB - Twenty-nine patients with an incomplete (26) or a complete (3) amputation of the upper extremity proximal to the wrist with revascularization or replantation were reviewed. Limb survival rates were very high (93%) despite the severity of the injuries. All patients regained some useful hand function, with 76% attaining a group I or group II (Chen criteria) functional result. Bone shortening osteotomies are a helpful way to reduce the soft tissue defect size. In contrast to earlier studies, clear correlations between the level of injury, degree of nerve lesion, bone pathology, and the number of major nerves involved, and the functional outcome achieved were not found. There was a weak correlation between the type of wound and the functional recovery ultimately obtained. PMID- 1880355 TI - The use of the lateral arm flap in upper limb surgery. AB - Twenty patients who had had upper limb reconstruction using the lateral arm free microvascular flap are reviewed. The size of the flap, modifications to the flap, and complications were documented. There was one flap failure, and nine flaps required surgical thinning at a second procedure. This sole disadvantage was outweighed in clinical usage by the advantages and versatility of the lateral arm flap. PMID- 1880356 TI - Revascularization of a finger with a thenar mini-free flap. AB - A devascularized index finger with a soft tissue defect on its palmar side was managed by using a small free flap raised at the level of the metacarpophalangeal joint of the thumb. The radial digital artery was included in the flap and used to revascularize the index finger, and a palmar vein was used to drain the flap. This resulted in minimal donor side morbidity. PMID- 1880357 TI - Kaposi's sarcoma in the hand seen as an arteriovenous malformation. AB - A case of Kaposi's sarcoma, which was initially thought to represent an arteriovenous malformation, is described. Angiographic findings were misleading, and careful histopathological analysis of such lesions is advocated so that correct treatment may be carried out. PMID- 1880358 TI - Musculus lumbricalis pollicis. AB - In six cases of thumb hypoplasia, a muscle arose from the anomalous flexor pollicis longus tendon in the region of the metacarpophalangeal joint, passed across the narrowed first web space, joined the lumbrical belly of the index, and inserted into the extensor hood of that digit. Traction on the muscle at its origin in the thumb produced extension of the interphalangeal joints of the index finger. Because of its attachments and action, this muscle has been given the name musculus lumbricalis pollicis. Not previously described in this form, the muscle is significant in hypoplasia because its contraction will act to narrow the already deficient first web space. In all instances where it was present, the musculus lumbricalis pollicis was excised. PMID- 1880359 TI - Pollex abductus in hypoplasia and duplication of the thumb. AB - Pollex abductus is an anomaly in which the flexor pollicis longus attaches not only at its customary insertion, but also into the extensor by a tendon that passes around the radial aspect of the thumb. Contraction of the anomalous flexor abducts the thumb. In the original report, the anomaly occurred in thumb hypoplasia. A similar anomaly is reported in 11 hypoplastic thumbs (35.5% of all cases) and in 9 cases of radial polydactyly (21.4%). The common feature was poor definition of the interphalangeal skin crease, with complete absence of active flexion of that joint. All patients were treated surgically; 13 before the age of 10 months, with correction of the duplication and the hypoplasia, and in the latter with elimination of the abduction deformity and restoration of opposition. The anomalous connection was excised in all patients. Active interphalangeal joint motion after reconstruction of the hypoplastic thumbs averaged 21 degrees. PMID- 1880360 TI - Cutaneous mesenchymal hamartoma in the palm. AB - A case of congenital, solitary, cutaneous mesenchymal hamartoma in the palm of the left hand is reported. The mass was composed mainly of an intimate mixture of fibrocollagenous bundles and islands of mature fat cells, distorted blood vessels with smooth muscle in the wall, and eccrine sweat glands. Many mast cells were scattered throughout the fibrocollagenous bundles. The mast cell may be an important cell in this hamartoma. PMID- 1880361 TI - Symptomatic congenital coalition of the pisiform and hamate. AB - Recent reports have shown that carpal coalition, previously regarded as an asymptomatic congenital anomaly, may be an unusual occult cause of wrist pain. Two cases are presented as the first reported examples of congenital piso-hamate fusion creating symptoms due to associated arthritis or occult fracture. PMID- 1880362 TI - Extra digit arising from the forearm. AB - A patient with an extra digit arising from the forearm is reported. This is the first such case reported in the English-language literature. PMID- 1880363 TI - Long-term follow-up of primary flexor pollicis longus tenorrhaphies. AB - This study retrospectively analyzes primary flexor pollicis longus repairs. Ninety-four patients were identified and had extensive chart review. Thirty patients returned for follow-up (mean of 6.8 years) interview, range of motion, and strength testing. At follow-up, interphalangeal active range of motion, metacarpophalangeal active range of motion, and carpometacarpal active range of motion was 68 degrees, 48 degrees, and 46 degrees, respectively. Comparisons between active range of motion for the injured and noninjured hands revealed percentage differences of 71, 82, and 96% for the interphalangeal, metacarpophalangeal, and carpometacarpal joints. The percentage differences between active range of motion and passive range of motion for the injured metacarpophalangeal and interphalangeal joints were 71% and 75%. Injured thumbs had averages of 6.7, 7.0, 5.4, and 30.6 kg for the key, chuck, thumb-index pinches and JAMAR grip mean. The percentage differences of injured to uninjured hands in these tests were 91%, 84%, 92%, and 92%. Factors that appear to have a consistently negative effect on outcome include mechanism of injury and associated damage. Factors that did not uniformly affect outcome included zone of injury, age, sex, and postoperative splinting. PMID- 1880364 TI - A flexor tendon rupture in the palm of the hand. AB - Traumatic, subcutaneous ruptures of flexor tendons in the hand are infrequent findings in clinical practice. They usually occur at the bony insertion or at the musculotendinous junction. Intratendinous ruptures are reported almost only in association with underlying pathologic conditions. We report a case of subcutaneous rupture through the healthy substance of the profundus flexor tendon of the small finger in the palm of the hand, which was associated with a complete tendinous fusion between the deep flexor of the ring and small finger up to the lumbrical insertion. PMID- 1880365 TI - Tendon excursion and dehiscence during early controlled mobilization after flexor tendon repair in zone II: an x-ray stereophotogrammetric analysis. AB - The effect of different methods on early controlled mobilization of the flexor profundus tendon regarding tendon excursion and dehiscence was examined during treatment of 20 tendons in 18 patients. An application of radiographic stereophotogrammetric analysis on movements of tendon tissue was developed and the tendons studied during the early postoperative period. Considerable differences of tendon excursion were found between the various mobilization methods and were dependent on the level of injury within zone II. The use of a mobilization method that includes a component of controlled active flexion is suggested for injuries at the A3 and A4 levels. This radiographic stereophotogrammetric analysis method developed for tendon excursion and dehiscence is new and provides knowledge that cannot be obtained in any other way. PMID- 1880366 TI - Complications experienced in the rehabilitation of zone I flexor tendon injuries with dynamic traction splinting. AB - A retrospective review of all flexor tendon repairs done between January 1985 to June 1987 determined the complication rate with our method of rehabilitation. One hundred sixty-three flexor tendon lacerations in 83 patients were reviewed. Follow-up ranged from 6 to 42 months. All patients participated in the same 12 week rehabilitation protocol. All patients had passive motion exercises of the interphalangeal joints in the first 2 weeks. We believe that passive stretching of zone I injuries during the first 2 weeks contributed to the zone I complication rate. Of the 20 patients with zone I tendon-to-tendon repairs, 7 patients had significant complications. The 35% complication rate found with zone I injuries has prompted us to modify our postoperative rehabilitation protocol in zone I injuries. PMID- 1880367 TI - Fibroblast chemotaxis after tendon repair. AB - Healing canine flexor tendons were treated with early controlled passive mobilization. The repair site and proximal and distal tendon stumps were stained for fibronectin and examined by light microscopy at three, seven, eleven, and seventeen days. Fibronectin increased dramatically in the epitenon adjacent to the repair site seven days after repair, a time when epitenon cellular activity was at its peak. By seventeen days, fibronectin staining had decreased substantially, both at the repair site and in the tendon stumps. A delayed increase in fibronectin activity was noted in the endotenon adjacent to the repair site. Fibronectin production appears to be an important component of the early tendon repair process. Fibroblast chemotaxis and adherence to the substratum in the days after injury and repair appears to be related directly to fibronectin secretion. This study is the first to provide documentation of fibronectin localization in a clinically relevant tendon repair model. PMID- 1880368 TI - An experimental model for the study of canine flexor tendon adhesions. AB - An experimental model for the study of canine flexor tendon adhesions was designed using a standardized crush-abrasion injury, meticulous sheath closure, and three-week limb immobilization. Ten animals in the experimental protocol were evaluated for visible adhesion formation. With use of a flexor tendon adhesion rating scale, consistent adhesion formation was documented with an average score of 10.4 +/- 2.1 (range, 0 to 12). Five additional animals had biomechanical testing. Applying an increasing load to the proximally divided profundus tendon (0 to 10 Newtons), it was found that the angle of distal interphalangeal joint motion and the displacement of the toe were significantly decreased, and the work generated significantly increased in the experimental versus control digits (p less than 0.05). The consistent production of visible adhesions thus correlates with biomechanical impairments in toe motion and work. The study of agents aimed at diminishing flexor tendon adhesions will thus be facilitated by this reliable model. Systemic or intrasheath administration of agents will be possible. PMID- 1880369 TI - Cyclic stress analysis of flexor tendon repair. AB - A method of evaluating flexor tendon repair techniques with the use of cyclic testing is presented. This type of evaluation complements the presently used load to-failure tests by providing more detailed information about gap formation at the repair site. During load-to-failure testing in this study, core sutures alone demonstrated initial gap formation at 0.85 kg tensile force or more; yet on cyclic testing all techniques demonstrated gap formation of 1.9 mm or greater at 0.5 kg tensile force. Thus cyclic testing demonstrated gap formation not readily apparent on load-to-failure testing. An epitenon stitch placed circumferentially around the laceration site added strength in both load-to-failure and cyclic tests, and significantly reduced gap formation regardless of the core suture technique. PMID- 1880371 TI - A second-stage flexor tendon reconstruction after 18 years. AB - A case of successful staged tendon reconstruction for treatment of a zone II flexor tendon injury with a delay of 18 years between Hunter rod placement and secondary tendon grafting is presented. In this case, the prolonged interval was not detrimental to a successful outcome. PMID- 1880370 TI - The plantaris tendon graft: an ultrasound study. AB - To assess the value of ultrasound in imaging the plantaris tendon, ultrasounds were done on 26 legs in 25 patients who had a variety of surgical procedures on the posterior leg. Eighteen ultrasounds were done and interpreted before operation and eight after operation by a radiologist. The sonographic results were compared with the status of the plantaris as determined at surgery. The plantaris was present in 21 of 23 patients for a prevalence of 91%. Eighteen plantaris tendons were well visualized on ultrasound for a sensitivity of 86%. Of the three false-negative results, two occurred with thinned plantaris tendons that were less than 2 mm thick and hence considered inadequate for grafting. Therefore, the sensitivity for detecting a tendon suitable for grafting was 95%. All patients with positive studies had a plantaris tendon present for a specificity of 100%. A learning curve for the radiologist was demonstrated. Ultrasound appears to be effective in the preoperative imaging of the plantaris tendon. PMID- 1880372 TI - Pathobiology of the human A1 pulley in trigger finger. AB - Eighty-nine A1 pulleys from 65 patients with trigger digits and 20 control A1 pulleys from fresh-frozen cadavers were studied comparatively with histology, immunohistochemistry, and transmission electron microscopy. In both normal and pathologic specimens, the A1 pulley was composed of two layers: an outer, vascularized, convex layer and an inner, concave, friction, flexor tendon gliding layer. In the latter, the cells and adjacent matrix had several characteristics of fibrocartilage, including chondrocytes. In trigger digits, the number of chondrocytes and adjacent extracellular matrix was significantly increased when compared with controls. There was no evidence of a synovial cell layer on the surface of the A1 pulleys in either normal or trigger digits. We conclude that the underlying pathobiological mechanism for triggering at the A1 pulley is characterized by a fibrocartilage metaplasia. PMID- 1880373 TI - Biomechanics of pulley reconstruction. AB - The biomechanics of the reconstructed flexor retinacular pulley system are poorly defined. We used a mathematical theoretical model, confirmed by a cadaver model, and a clinical radiographic model to evaluate a variety of different joint and pulley combinations. We examined twenty-four sets of radiographs of 12 fingers in 9 patients for whom excursion was measured and predicted by the mathematical model. The 30 pulley combinations evaluated in the in vitro cadaver model showed statistical correlation with the biomechanical mathematical model. Recommendations of clinical application on the basis of this information include the following: (1) Two pulleys should be placed, one proximal and one distal to each joint. (2) These two pulleys should be balanced about the joint axis both in distance from the axis and in pulley height. (3) They should be positioned at the edge of the flare of the metaphysis. (4) The three individual joints can be balanced, one to another, by maintaining minimal bowstringing at all three joints. In this way, the relative excursion at the joint and torque at the joint will be maintained in a physiological ratio as close to normal as possible. PMID- 1880374 TI - Compression syndromes in reflex sympathetic dystrophy. AB - Over an 8-year period we treated 93 cases of reflex sympathetic dystrophy. The initial treatment consisted of long-acting intramuscular corticosteroids and active exercises. Twenty-two patients who did not respond significantly to this treatment had carpal tunnel syndrome. In addition, five had cubital tunnel syndrome, one had ulnar tunnel syndrome, and one had a herniated disk of the cervical spine. All nerves were decompressed with significant improvement in the patient's condition. Pain was relieved in all except three who had mild pain. Motion of the proximal interphalangeal joint improved from an average of 35 degrees before operation to 76 degrees after operation. Grip strength improved from an average of 4 pounds to 27 pounds. PMID- 1880375 TI - Accessory palmaris longus muscle causing ulnar nerve compression at the wrist. AB - An accessory palmaris muscle that arose from the base of the fifth metacarpal passed proximally and inserted into the palmaris longus tendon. In its course it compressed the ulnar nerve and vessels. It was detached proximally and folded on itself to provide hypothenar bulk. The entrapment symptoms were relieved. PMID- 1880376 TI - Ulnar nerve compression in Guyon's canal caused by calcinosis in scleroderma. AB - Calcium deposits in Guyon's canal secondary to scleroderma caused low ulnar nerve paralysis in a 70-year-old white woman. Excision of calcium deposits resulted in rapid alleviation of pain. After nerve regeneration, the patient's clawing disappeared, and she was able to abduct and adduct all digits. PMID- 1880377 TI - Radial nerve entrapment at the elbow: surgical anatomy. AB - The surgical anatomy of interest in the posterior interosseous nerve syndrome was studied to shed light on the ramifying pattern of the radial nerve, the number of its muscular branches and their branching levels, and to pinpoint the location of the fibrous bands that may cause radial nerve entrapment. The fibrous arch of the supinator muscle (arcade of Frohse) was found to lie 3 cm to 5 cm below Hueter's line, that of the extensor carpi radialis brevis muscle lay 0.5 cm to 1 cm proximal to the arcade of Frohse. Symptom patterns in terms of muscle weakness caused by radial nerve entrapment at different levels were also evaluated. PMID- 1880378 TI - Radial nerve entrapment by the lateral head of the triceps. AB - A case of slowly progressive radial nerve entrapment of spontaneous onset is presented. Surgical exploration revealed compression of the radial nerve by a musculotendinous arch of the lateral head of the triceps. Relief of signs and symptoms did not ensue. PMID- 1880379 TI - Compression neuropathy of the motor branch of the median nerve caused by palmar ganglion. AB - We describe a palmar ganglion producing paralysis of the motor branch of the median nerve; such a case has not been reported previously. Ultrasonography was useful for preoperative diagnosis. PMID- 1880380 TI - Synovial histology in carpal tunnel syndrome. AB - This study investigates the relationship between idiopathic carpal tunnel syndrome and tenosynovial histology, specifically inflammation. Tenosynovial biopsy specimens from 177 wrists were obtained from patients at carpal tunnel release, and a control group of 19 specimens was also obtained. Inflammation was present in only 10% of the patient specimens and was correlated with only one of the clinical and histologic factors studied, i.e., nerve conduction impairment. Edema, observed frequently (85%), was not correlated with inflammation. Vascular sclerosis was also found consistently (98%) and was correlated with patient age and degree of edema. Edema and vascular sclerosis occurred with significantly greater frequency and severity in the specimens of patients than in the control group. Fibrosis (3%) and synovial hyperplasia (1%) were uncommon findings. It is concluded that tenosynovitis is uncommon in patients undergoing surgery for treatment of idiopathic carpal tunnel syndrome. PMID- 1880381 TI - A method of removing threaded external fixation pins from bone. PMID- 1880382 TI - Quick fixation of skin grafts. PMID- 1880383 TI - Method of tendon labeling in forearm injuries. PMID- 1880384 TI - Digital sheath excision. PMID- 1880385 TI - Partial purification and characterization of a soluble acid phosphatase from the tapeworm, Hymenolepis diminuta. AB - An acid phosphatase activity (APA; EC 3.1.3.2) was demonstrated in homogenates of adult Hymenolepis diminuta. The APA was soluble based on the observation that it did not sediment at 130,000 g. APA was partially purified using a combination of differential centrifugation, ammonium sulphate precipitation, chloroform extraction, and gel and fast-protein-liquid-chromatography. This combination of techniques resulted in a preparation with a specific activity approximately 500 times greater than the crude enzyme preparation. The temperature and pH optima of the partially purified APA were 44 degrees C and pH 5.0. The enzyme appeared to be a monomer with a molecular weight of approximately 62,000. APA had a higher affinity for a greater activity towards aromatic than aliphatic phosphoesters, and phosphoryl transferase activity was demonstrable using 1-butanol and ethylene glycol as acceptors. APA was inhibited significantly by sodium dodecyl sulphate, fluoride, molybdate and tartrate, but CuSO4 and Fast Garnet GBC were poor inhibitors. The precise cellular localization and function of this enzyme remains unknown since it possesses characteristics of both cytoplasmic and lysosomal APA's of other organisms. PMID- 1880386 TI - Nonspecific immunomodulation influences resistance of mice to experimental infection with Mesocestoides corti and Ascaris suum. AB - The influence of nonspecific immunomodulation on the course of experimental infection was examined in larval cestodosis (Mesocestoides corti) and ascaridosis (Ascaris suum) in mice. Immunosuppressive treatment (with azathioprine or hydrocortisone) resulted in a decrease of resistance in both models. The subsequent administration of T-activin to immunosuppressed mice led to the restoration of resistance to a level equal to that of untreated control mice. The administration of different immunomodulators partially protected mice against M. corti (T-activin, thymomodulin) or A. suum (T-activin, thymomodulin, thymosin fr.5, bursa-activin) infection. The protective effect of different treatments did not correlate with the level of specific antibody in the sera of infected mice. These results, which confirmed the decisive role of T-cell immunity in the resistance to the helminth infections, raise the possibility of the use of immunomodulators (thymic preparations) in the immunoprophylaxis of helminthoses. PMID- 1880387 TI - In vitro effect of larval stages of Ascaris lumbricoides on human blood clotting. AB - The effects of larval stages of Ascaris lumbricoides on human blood clotting was studied in vitro. Extracts and excretory/secretory products of third-stage larvae (L3) and late third-stage larvae (LL3) cultured from ova obtained from infected patients were analysed for anti-coagulant activity. Prothrombin time (PT) was prolonged by the addition of either whole extract of L3/LL3 or ES products of L3/LL3 as compared to controls. Partial thromboplastin time with kaolin (PTTK) was also prolonged on the addition of either extracts of ES products of L3/LL3. The prolongation of PTTK was significantly higher with extracts/ES products of L3 when compared to the extracts/ES products of LL3 (p less than 0.005). Thrombin time (TT) was prolonged by extracts of L3/LL3 and their ES products. PMID- 1880388 TI - Factors influencing the egg production of Ascaris lumbricoides: relationship to weight, length and diameter of worms. AB - Fifty children aged 6 to 13 years and infected with Ascaris lumbricoides were selected for the study. The number of eggs laid daily by a female Ascaris increased with increase in its length, weight and diameter. Female worms became mature and started laying eggs when they reached a length of 118 mm. Adult female worms measuring 3.7 mm or more in diameter were found to be mature. The minimum weight of a worm producing eggs was 1.1 g. On average the number of eggs produced by the female decreased with increase in the worm load. PMID- 1880389 TI - The effect of praziquantel on the ultrastructure of Schistosoma margrebowiei. AB - The effect of various concentrations of praziquantel at different time intervals post-treatment on the ultrastructure of Schistosoma margrebowiei using scanning and transmission electron microscopy has been examined. The major changes involved blebbing of the entire surface tegument of both sexes (although more marked in males) together with vacuolation of the basal membrane accompanied by the development of membraneous whorls. These effects were progressively more marked with increased concentration and time of exposure resulting in severe erosion of the tubercles and collapse of the sensory organelles. Exposure of the underlying tegumental tissue resulted and paralysis and contraction of the suckers and neck region was apparent. Disruption of the subtegumental musculature and the appearance of vacuolation and membraneous whorl formation were seen. The gastrodermis was similarly affected and the S4 cells of the vitelline gland showed protein disruption of the vitelline droplets. Host cells were seen adhering to the surface of the worms following drug treatment and the synergism between PZQ and the action of the hosts immune system has been discussed. PMID- 1880390 TI - A study of an outbreak of schistosomiasis in two resettlement villages near Abeokuta, Ogun State, Nigeria. AB - Frequent reports of haematuria among resettlers at Ibaro and Abule-titun located close to a newly constructed reservoir, 20 km north-west of Abeokuta, Ogun State, Nigeria, prompted a pre-control survey to assess age and sex distribution of urinary schistosomiasis in the communities. 210 persons were examined at Ibaro and 145 at Abule-titun between April 1988 and February 1989. Overall prevalence was about 80% in both villages, and all age and sex groups examined were affected. The pattern of infection in both villages was similar, prevalence being high in all age and sex groups, and, unlike most endemic communities, the rate of infection was not significantly higher among the 5-14 year age groups. Intensity of infection was also high in all age and sex groups with mean range egg output of between 73 +/- 73 and 2016 +/- 3875 ova/10ml urine at Ibaro and between 231 +/ 122 and 1340 +/- 1786 ova/10ml urine at Abule-titun. This is attributed to an occupation-related high rate of human water contact in both villages. PMID- 1880391 TI - Evidence for selective differences in single-band polytene chromosome polymorphism in Sciara ocellaris. AB - Sciara ocellaris (Bradysia tritici) is a dipteran species characterized by an extensive polymorphism of structural modifications of single bands occurring in the polytene chromosomes. In this experiment we obtained estimates of egg-to adult viabilities in relation to the genotypes determined by 15 different loci. In spite of the presence of considerable levels of linkage disequilibrium possibly generated by random sampling genetic drift, it is suggested that at least one out of 15 polymorphic modified chromomeric loci is maintained in the population by an overdominance mechanism. PMID- 1880392 TI - Reappraisal of the genetic map of Chlamydomonas reinhardtii. AB - In Chlamydomonas reinhardtii, we have found that linkage groups XII and XIII define only a single linkage group and that linkage groups XVI and XVII also define a single linkage group. The interdigitation of the genetic maps of linkage groups XII and XIII and of XVI and XVII is presented. At present, 17 linkage groups that display Mendelian segregation have been identified in C. reinhardtii. PMID- 1880393 TI - Pollen migration in predominantly self-fertilizing plants: barley. AB - In barley, a heavily self-fertilizing species (approximately 99%), most outcrosses occur between plants that grow closely adjacent to each other. Outcrosses have been detected only rarely between plants that are separated by a meter or more. In this article we present evidence that outcrosses can occur at distances up to 60 m and we discuss the implications of this longer-distance pollen migration on the maintenance of the genetic integrity of pedigreed stocks and experimental populations. PMID- 1880394 TI - The chromosomes of three species of the Montium subgroup of Drosophila. AB - Chromosomes of Drosophila truncata, D. nagarholensis, and D. agumbensis of the montium subgroup were analyzed to record the divergence attained at the level of metaphase complement and the extent of inversion polymorphism. Results are presented in this article. PMID- 1880395 TI - Assignment of two enzyme loci to the X chromosome of Anopheles quadrimaculatus species A. AB - Analysis of isozyme variability in four natural populations of Anopheles quadrimaculatus Species A indicated that the loci for Malic enzyme (Me) and Mannose phosphate isomerase-1 (Mpi-1) are on the X chromosome. There were female heterozygotes, but no male heterozygotes were observed. Strains fixed for fast- and slow-migrating allozymes were devised and crossed. Progeny phenotypes conformed to expectations for sex linkage; female progeny were heterozygous, and male progeny were hemizygous for the maternal allele. The three-point cross, using the Me and Mpi-1 loci with the sex-linked mutant rose eye (ro), established the gene sequence Mpi-1-11.1-Me-40.8-ro. PMID- 1880396 TI - Two doses of the paternal Tme gene do not compensate the lethality of the Thp deletion. AB - The hairpin-tail (Thp) deletion in chromosome 17 is lethal when it is inherited from the mother, whereas heterozygotes with Thp deletion that is paternal in origin are viable. The lethal effect of maternal Thp is due to a deficiency of the Tme gene that is located in the Thp-deleted region. In this article we describe analysis of the viability of mice with tertiary trisomy of chromosome 17, Ts(17(16]43H, with different doses of the paternal and maternal Tme alleles. We demonstrate that the presence of an additional copy of the region with the Tme gene in the female gamete entirely compensates maternal Thp lethality. We failed to compensate the absence of the Tme gene from the chromosome of maternal derivation by two doses of Tme derived from the father. Thus evidence was obtained indicating that there are significant differences between the activities of the paternal and maternal alleles of the Tme gene due to chromosome imprinting. PMID- 1880397 TI - COMPVAR: a computer program for iteratively estimating components of variance in crossbreeding experiments. PMID- 1880398 TI - A canon, a choirboy, and homosexuality in late sixteenth-century Italy: a case study. AB - Documents in the Archivio di Stato of Florence allow for the reconstruction of a case of clerical sodomy involving a canon and a choirboy of the Church of Our Lady of Loreto in the year 1570. The story can be followed in detail from its beginning to its tragic conclusion through letters sent to the Cardinal Protector of Loreto and transcripts of interrogations carried out in the town itself. PMID- 1880399 TI - The Biblical Prohibition of homosexual intercourse. PMID- 1880400 TI - Thoreau's sexuality. AB - Although Henry David Thoreau (1817-1862) has often been described as lacking in sexual drive or at most a rather reluctant heterosexual, a close study of his life and writings indicates the presence of a pronounced vein of homoeroticism- although there seems to be no concrete evidence of any homosexual activity on his part. Cognizance of that homoeroticism helps one to understand many elements of his life and writings and suggests that his intense love of nature may have resulted from sublimation of that homoeroticism. PMID- 1880401 TI - Factors affecting the coming out process for lesbians. AB - Cass' model (1979) of identity development and her Stage Allocation Measure (1984a) were assessed to determine their utility in describing the subjective experience of coming out as a lesbian and whether proposed stages could be tied to behavioral correlates of the Openness Questionnaire (Graham, Rawlings, & Girten, 1985). The process was considered in terms of a woman's differentiation from her family, sex-role attitudes, and levels of internalized homophobia. Eighty-one lesbians anonymously completed questionnaires. The results suggest that subjective labeling and behavior are congruent, but that rate of progression through stages does not imply integration of behavior. Four patterns of identity development were identified which suggest that relevant stages, speed of development, and stage attainment are characteristic of certain women. Intergenerational intimidation was significantly related to stage development, sex-role attitudes, openness behavior, and levels of internalized homophobia. PMID- 1880402 TI - The relation of gender and sexual orientation to measures of masculinity, femininity, and androgyny: a further analysis. AB - Data from a survey of 58 gay men and 58 lesbians are compared to college men and women on Spence and Helmreich's (1978) Personality Attributes Questionnaire measures of masculinity, femininity, and androgyny. Lesbians had higher M scores than college women, and gay men had lower M scores than college men, with F scores being similar across sexual orientation groups, within gender. Androgyny measures differed only by gender, not by sexual orientation. Further analysis shows that lesbians' high M scores come largely from their high self-ratings as independent, while college men's high M scores reflect strong competitiveness. Questions are raised about the validity of these measures for comparing these groups. PMID- 1880403 TI - WHO issues new estimates on global AIDS situation. Paediatric AIDS cases send estimates soaring. PMID- 1880404 TI - Family studies in common variable immunodeficiency. AB - The occurrence of cancer, immunodeficiency, and diseases with possible autoimmune aetiology were studied in 355 blood relatives of 12 patients with common variable immunodeficiency (CVID). The family members were identified through the patients and interviewed after completing a questionnaire, their diseases were medically confirmed by local general practitioners. In two families consanguineous marriages were identified with the coefficients of inbreeding of 0.03125 and 0.01563, respectively: one patient, a dizygotic twin of an unaffected sister, was a granddaughter of first cousins, the second patient was the third daughter of second cousins. These cases of CVID strongly support the autosomal recessivity of the underlying genes. One male patient with CVID was shown to be related to a patient with X-linked hypogammaglobulinaemia, both sharing a common carrier. The different clinical courses of their diseases suggest two genetically determined immunodeficiencies and genetic heterogeneity. No family had an unusual clustering of cancer. The occurrence of tumours in the blood relatives of CVID patients was not significantly higher than in the relatives of spouse controls. Immunological examination of 30 first degree relatives of the CVID patients revealed three children (2 males and 1 female) with selective IgA deficiency, in one boy combined with elevated serum IgE level. Four relatives with rheumatoid heart disease, 12 cases of gastric or duodenal ulcer, and 14 relatives with thyroid disease represented the most often encountered diagnoses with a possible autoimmune component in their aetiology. PMID- 1880405 TI - On the clinical importance of Dientamoeba fragilis infections in childhood. AB - Clinical and laboratory findings among 123 paediatric patients infected by intestinal protozoa were analysed. Dientamoeba fragilis (D. f) was found in 102 cases. The other patients proved to be carriers of Giardia lamblia or of mixed infections with several protozoa. Acute and recurrent diarrhoea have been found to be the most common symptoms, whereas abdominal pain was most common in children with chronic infections. Peripheral blood eosinophilia was seen in a third of the children with dientamoebiasis. Metronidazole, oxytetracycline, doxycycline, and erythromycin were effective drugs in the treatment of D. f. infections. The therapy coincidentally led to the elimination of protozoal infections as well as the abdominal complaints. These results underline the pathogenic role of D. f. in children with gastrointestinal symptoms. PMID- 1880406 TI - A case of shigellosis caused by Shigella dysenteriae type 1 and Shigella flexneri type 5B. AB - Shigella dysenteriae type 1 and Shigella flexneri type 5b strains were isolated as causative agents of bacterial dysentery in a patient having visited South-East Asia. Both strains are a rare finding for Bulgaria. S. dysenteriae 1 strains have not been isolated since 1962, and there were only single isolates of S. flexneri 5b. The strains were of the same antibiotic resistance patterns. Conjugation experiments showed that resistance is determined by transferrable R-plasmids having identical characteristics. It is assumed that in the patient's gut transfer of an R-plasmid occurs from E. coli of the normal flora to the pathogenic shigellae. PMID- 1880407 TI - T-2 toxin degradation by micromycetes. AB - The biodegradation of T-2 toxin was studied by strains of micromycetes which were isolated from the environment. The 26 tested strains were divided into three groups. Group contains strains which degraded T-2 toxin very fast. This toxin could not be chromatographically determined in the medium even after 48 hours of incubation and the antifungal activity of residua against Kluyveromyces fragilis CCY-51-1-2 was low or zero. There were strains of Alternaria sp., Ulocladium sp., Aspergillus candidus, Cladosporium cladosporioides, Rhodotorula sp., Aspergillus flavus and Cladosporium macrocarpum. Group II contains with a low activity and in group III the results were variable and non stable. PMID- 1880408 TI - Some differential growth characteristics of Vibrio cholerae and Vibrio metschnikovii in liquid medium. AB - Some differential growth characteristics for Vibrio cholerae and Vibrio metschnikovii were examined in a liquid medium with reference to pH and ionic strength, as well as temperature and length of incubation. The purpose was to discover the combination of the above conditions which would enable selective replication of V. cholerae accompanied by suppressed growth of V. metschnikovii. Preliminary routine verification of one combination of conditions which involves a lengthening of incubation to 22 h at a heightened temperature of 41 degrees C in sewage water samples pointed to the possibility of rapid and simple quantitative demonstration of V. cholerae. PMID- 1880409 TI - Bacterial isolates and drug susceptibility tests at Kaffa Regional Public Health Laboratory, south west Ethiopia. AB - A two year period bacteriological data was analysed and the frequent bacterial isolates from different clinical specimens included: S. aureus, 25% E. coli, 15%; Proteus spp 14%; Citrobacter-Enterobacter group, 10% coagulase negative Staphylococcus species, 9%; and other miscellaneous bacteria each less than 9%. The majority of the bacterial isolates were resistant to commonly available antimicrobial agents like tetracycline, ampicillin, and chloramphenicol. PMID- 1880410 TI - Latex agglutination and hemagglutination tests for the rapid identification of methicillin sensitive and methicillin resistant Staphylococcus aureus. AB - Ten latex agglutination (LA) and hemagglutination (HA) kits for the identification of Staphylococcus aureus were compared with reference methods for their reliability and performance. The ten commercial kits consisted of Accu Staph, Bacto-Staph, Hemastaph, Staphaurex, Staph-Latex, Staphylochrome, Staphyloslide, Staph-Rapid, Sero-Stat and Veri-Staph. The conventional methods included slide coagulase test, tube coagulase test (4 hr, 24 hr), thermonuclease and growth on mannitol salt agar (MSA). A total of 583 clinical isolates of staphylococci were used and all the kits correlated well with the conventional methods (93.1-99.4% sensitivity) in their ability to identify both methicillin sensitive (MSSA) and methicillin resistant S. aureus (MRSA). Although all were rapid, easy to perform and simple to interpret, Staphaurex and Staphyloslide gave the best sensitivities and specificities. PMID- 1880411 TI - Typhoid fever survey in two localities in Vietnam. AB - As a part of multipurpose health survey of the population in Vietnam the antibodies against S. typhi were determined by the micromethod using haemagglutination test (O-antigen 9, 12) and agglutination test using standard H diagnostic antigen (d). Totally 292 sera were examined, 139 from Duyen Thai village and 154 from Mai Chau. The data on vaccination against typhoid fever are recorded only in 102 persons. The positivity on Vi antibodies is very high--70% in Duyen Thai and 47% in Mai Chau. This finding is significant according to the high titres in the carriers of S. typhi. The titres of all antibodies are lower in Mai Chau area situated in mountains then in crowded lowlands of Duen Thai. The level of antibodies is decreasing with age. The frequency distribution of antibodies by age proves endemicity of the disease in area, where a large part of population is infected already before reaching 20 years of age. The effectivities of vaccination is discussed. PMID- 1880412 TI - Antibodies to lymphocytic choriomeningitis virus in wild rodent sera in Egypt. AB - Specific antibodies to lymphocytic choriomeningitis (LCM) virus were detected in sera of wild rodents trapped in different regions of Egypt. The highest proportion of positive sera (11.5%) was found in Sinaa Governorate of the Asian Continent, followed by Sharkia Governorate (5.6%) adjacent to Sinaa and Giza Governorate (1.8%). In Upper Egypt, however all 610 rodent sera collected in Aswan, Red sea Pernees and New Valley adjacent to Sudan were negative. The highest percentage of positive sera was in Rattus rattus frugivorus and Mus musculus species. PMID- 1880414 TI - Immunization with soluble murine CD4 induces an anti-self antibody response without causing impairment of immune function. AB - The T cell surface molecule CD4 (L3T4 in mouse) is important in the T lymphocyte response to Ag presented in association with MHC class II molecules. To examine the role of CD4 in immune function, we expressed a soluble form of murine CD4 by deleting the transmembrane and cytoplasmic regions of the L3T4 gene and transfecting the altered gene into Chinese hamster ovary cells. The recombinant soluble mouse CD4 (smCD4) retained the native conformation of the external portion, as indicated by the binding of L3T4 mAb. In vitro, smCD4 did not inhibit class II-dependent, Ag-specific, T cell proliferation or MLR, even at concentrations 300-fold greater, on a molar basis, than that of anti-CD4 mAb. Immunization of mice with smCD4 induced a strong anti-CD4 response. These antibodies showed some binding to native cell surface CD4, indicating that immunization with smCD4 generated an anti-self response. Analysis of lymphoid cells from spleen, lymph node, and thymus of smCD4-treated mice revealed no alteration in subset phenotypes. Also, Th cell function, as measured by response to soluble Ag, was not compromised. Thus, smCD4 did not inhibit T cell activity in vitro, and the autoimmune response arising from immunization with smCD4 had no apparent consequences for normal immune function. PMID- 1880413 TI - B cell triggering by bacterial lipopeptide involves both translocation and activation of the membrane-bound form of protein kinase C. AB - B cell activation by the lipopeptide trispalmitoyl-cysteinyl-alanyl-glycine (TPP), the biologically active moiety of bacterial lipoprotein, results in protein kinase C (PKC) translocation from the cytosol to the plasma membrane, as well as a significant increase in the activity of membrane-associated PKC that can be observed by in vitro incubation with TPP of partially purified PKC at calcium concentrations in the range of those prevailing in unstimulated B cells. TPP does not affect either the phosphoinositide turnover or the cytosolic-free calcium concentration, but promotes an increase in the intracellular pH that can be blocked by the PKC-inhibitors staurosporine or H-7. Moreover, incubation of B cells with staurosporine suppressed the proliferative response promoted by TPP at a half-maximum effective dose of 16 nM. Activation by TPP of PKC isoenzymes resolved after hydroxylapatite chromatography revealed that the resulting beta I/beta II isoenzyme was more sensitive than the alpha isoenzyme. These results suggest that TPP might mediate B cell activation via interaction with the membrane-associated fraction of PKC. PMID- 1880415 TI - Histologic analysis of T lymphocyte activation in reactive lymph nodes. AB - As an approach to defining the anatomic sites of T cell activation in situ, we have developed an immunocytochemical stain for IL-2, a T cell-derived cytokine synthesized shortly after Ag-induced activation. Analysis of lymph nodes from mice immunized with keyhole limpet hemocyanin emulsified in CFA demonstrates that the IL2+ cells appear in a perivascular location 4 days after antigenic challenge. After germinal centers develop, IL-2+ cells are situated in a parafollicular pattern. Serial sections stained for different types of APC, including B cells, interdigitating dendritic cells, and macrophages, demonstrate a close physical association between IL-2+ cells and macrophages. These findings may have important implications for defining how APC bearing processed Ag and Ag specific T cells interact in the complex environment of lymphoid tissues. PMID- 1880416 TI - Shedding as a mechanism of down-modulation of CD14 on stimulated human monocytes. AB - CD14, expressed on the surface of monocytes as a phospholipid-linked protein, is a receptor for serum LPS binding protein/LPS complex. It was specifically down modulated after stimulation of monocytes by physiologic activating/differentiating agents such as bacterial LPS and IFN-gamma, by the pharmacologic agents PMA and calcium ionophore A23187, and by anti-CD14 antibodies. The down-modulation was almost totally blocked at 4 degrees C or at pH 4.5 and markedly inhibited by the protease inhibitors diisopropylfluorophosphate and PMSF. A soluble labeled CD14 was isolated from culture supernatant of surface iodinated monocytes after their activation, indicating that CD14 is shed from the cell surface rather than internalized. The size of the soluble CD14 shed from the monocytes in vitro was smaller than that of either the membrane-bound form or a soluble CD14 cleaved from the cell surface by phosphatidyl inositol-specific phospholipase C, but identical to the size of one of the two major soluble CD14 forms normally found in human serum. These data suggest that CD14 shedding induced by monocyte stimulation may play an important role in the regulation of surface CD14 expression. PMID- 1880417 TI - Alpha-chains of IgM and IgD antigen receptor complexes are differentially N glycosylated MB-1-related molecules. AB - The major B cell Ag receptors, membrane (m) IgM and mIgD, are noncovalently associated with disulfide-linked heterodimers of alpha, beta, and gamma glycoproteins. The beta and gamma chains have apparent molecular masses of 37 and 34 kDa, respectively, and are associated with both mIgM and mIgD. Receptor alpha chains, however, exhibit Ig isotype specificity. IgM-alpha and IgD-alpha have apparent molecular masses of 32 and 33 kDa, respectively. Recently, the alpha chain of the IgM Ag receptor complex was identified as the product of the mb-1 gene, and the beta and gamma chains were characterized as products of the B29 gene. The failure of mb-1 cDNA to hybridize with mRNA from J558 delta m2.6 plasmacytomas expressing surface mIgD in association with IgD-alpha has led to the conclusion that IgM-alpha and IgD-alpha are not closely related. In this report we have used protein biochemical methods to characterize differences in the mIgM- and mIgD-associated alpha chains. In addition to a slightly greater apparent m.w., IgD-alpha was slightly more acidic than IgM-alpha. The alpha chains had nearly identical proteolytic peptide maps, and were also noted to have multiple loci of identity with MB-1 based on amino terminal sequencing and immunoblotting. In an attempt to determine whether the alpha chains differed as a result of differential posttranslational modification, they were compared after deglycosylation with N-glycanase. The results indicate that the apparent m.w. as well as isoelectric point differences are primarily due to differential N-linked glycosylation. These studies indicate that IgM-alpha and IgD-alpha are products of the mb-1 gene or closely related genes. PMID- 1880418 TI - Expression of stress proteins in human mononuclear phagocytes. AB - The heat shock/stress response is characterized by the induction of several highly evolutionarily conserved proteins during thermal stress, chemical stress, or glucose starvation. It has recently been recognized that members of the stress protein family are synthesized constitutively and subserve functions that are critical to protein folding during intracellular transport. In this study we examined the expression of heat shock/stress proteins in human mononuclear phagocytes, cells dependent on intracellular transport for Ag processing, Ag presentation, generation of reactive oxygen intermediates, and secretion of proinflammatory and antiinflammatory polypeptides. The results indicate that there are distinct patterns in expression of individual members of the highly homologous SP70, SP90, and ubiquitin gene families during different stress states. There is a marked increase in expression of the heat-inducible form of SP70 and SP90 in human monocytes during heat shock. Expression of GRP 78/BiP and GRP 94 increases predominantly during glucose starvation but also increases during heat shock. Ubiquitin gene expression increases during both heat shock and glucose starvation. There is no change in synthesis of the constitutive form of SP 70 or of the ubiquitin activating enzyme E1 during heat shock or glucose starvation. Synthesis of the constitutive form of SP 70 and novel SP 90-like polypeptides increase during endotoxin-mediated inflammatory activation. One intracellular transport process of the mononuclear phagocyte, secretion of specific proinflammatory and antiinflammatory polypeptides, is affected by glucose starvation and by heat shock. PMID- 1880419 TI - Mast cells are critical for the production of leukotrienes responsible for neutrophil recruitment in immune complex-induced peritonitis in mice. AB - Mast cells are secretory cells strategically located in the vicinity of blood vessels where they can readily initiate and modulate various inflammatory processes, including plasma exudation and leukocyte infiltration. We have previously shown that 50% of the neutrophil influx during immune complex peritonitis in mice is due to mast cells. Eicosanoids are important mediators of various inflammatory processes including neutrophil infiltration. The possibility that mast cells are essential for the production of leukotrienes (LT) involved in the elicitation of neutrophils in immune complex peritonitis was investigated in mast cell-deficient, WBB6F1-W/WV, and normal, WBB6F(1-)+/+, mice. The time course and amounts of immunoreactive PGE2, 6-keto-PGF1 alpha, and TX3B2 released into the peritoneal exudates were similar in both sets of mice. LTB4 and LTC4 levels, however, were twofold higher in +/+ than in W/WV mice 2 h after stimulation. HPLC analysis of the peritoneal exudate confirmed the presence of leukotrienes. The 5 lipoxygenase inhibitor A-63162 blocked leukotriene production in a dose-dependent manner in both sets of mice. However, this compound caused a significant reduction (60%) of neutrophil infiltration only in WBB6F(1-)+/+ but not in the mast cell-deficient mice. Mast cell reconstitution of WBB6F1-W/WV mice restored the effect of A-63162 on PMN recruitment. These data suggest that mast cells in the vicinity of blood vessels are important for the synthesis of leukotrienes responsible for PMN recruitment. PMID- 1880420 TI - L-arginine-dependent macrophage effector functions inhibit metabolic activity of Mycobacterium leprae. AB - Recently, L-arginine has been shown to be a necessary substrate for murine activated macrophage-mediated tumor cytostasis and microbiostasis of certain fungi, bacteria, and intracellular protozoa. We report here the effects of the L arginine-dependent pathway of activated mouse macrophages (MO) on the obligate intracellular prokaryote, Mycobacterium leprae. Due to the inability to culture M. leprae in vitro, a simple, quantitative assay was employed to measure the metabolism/viability of M. leprae released from MO: the metabolic capacity of M. leprae to oxidize 14C-palmitic acid to 14CO2. Murine normal MO or MO activated in vitro with IFN-gamma or in vivo by injection with Corynebacterium parvum were infected with viable M. leprae freshly harvested from the footpads of nu/nu mice. Activated MO strikingly inhibited the metabolism of M. leprae; however, in L arginine-free medium or in medium containing L-arginase, the inhibitory effects of activated MO on M. leprae metabolism were abolished. The competitive inhibitor of L-arginine, NG-monomethyl-L-arginine, also blocked the inhibitory effects of activated MO for M. leprae, but the addition of supplemental L-arginine overcame the NG-monomethyl-L-arginine-induced block. Furthermore, in the culture supernatants, the levels of NO2-, an end product of L-arginine degradation, were directly proportional to the ability of the activated MO to inhibit M. leprae metabolism. These data present five lines of evidence that suggest that activated MO utilize the L-arginine-dependent pathway to cope with M. leprae. PMID- 1880421 TI - Mouse NKR-P1. A family of genes selectively coexpressed in adherent lymphokine activated killer cells. AB - NK cells are a subpopulation of large granular lymphocytes. They are able to recognize and lyse a wide variety of virally infected or neoplastic target cells without previous sensitization or MHC restriction. The molecules involved in target recognition and subsequent triggering of the killing process are still undefined. Recently, a 30-kDa protein highly expressed on rat NK cells and capable of mediating transmembrane signaling was identified and the gene coding for it cloned and sequenced. To better understand the role of this protein in NK cell-mediated cytotoxicity, we cloned its mouse homologue by cross-hybridization of the rat gene to a cDNA library generated from highly purified mouse lymphokine activated NK cells. Three messages, differing in size and sequence and encoded by different genes, are specifically cotranscribed in mouse NK cells. The protein products of this gene family express the lectin-like motif characteristic of type II transmembrane molecules. Both the rat and mouse proteins have conserved tyrosine and serine residues in their cytoplasmatic portion that are potential phosphorylation sites. They also share a sequence that could be the binding site of the P56lck tyrosine kinase. These observations are consistent with the signaling function hypothesized for these proteins. PMID- 1880422 TI - An enzyme immunoassay for human defensins. AB - We developed and optimized an enzyme immunoassay for human neutrophil defensins, cationic cysteine-rich peptides that participate in host defense and inflammation. The assay utilizes a sandwich design with a monoclonal capture antibody and a biotinylated monoclonal detecting antibody. Cetrimonium bromide is employed to obviate non-specific binding of defensins to surfaces. The assay has a sensitivity of 0.04-0.05 ng/ml and a working range of 0.05-10 ng/ml. PMID- 1880423 TI - pH sensitive liposomes provide an efficient means of sensitizing target cells to class I restricted CTL recognition of a soluble protein. AB - Exogenous antigens are normally endocytosed and enter the class II pathway of processing and presentation. It had been shown earlier that soluble antigen could be introduced into the class I pathway of processing and presentation by osmotic loading. In this report, we have demonstrated that OVA containing liposomes that destabilize on exposure to low pH, referred to as pH sensitive liposomes, could sensitize target cells to lysis by class I MHC-restricted OVA-specific CTL. However, OVA-containing pH insensitive liposomes, native OVA, or OVA subjected to the same protocol as was used to make the liposomes, failed to sensitize targets to OVA-specific CTL lysis. The pH sensitive liposomal approach was less toxic and more efficient (about 20-fold) in delivering than the osmotic loading approach. The pH liposome approach may prove valuable to study CTL recognition characteristics of less available proteins such as viral proteins. PMID- 1880424 TI - A new method of gene transfer into hematopoietic progenitors using liquid culture with interleukin-3 and interleukin-6. AB - The technique of gene transfer into hematopoietic cells is expected to offer a new form of therapeutics. As a result of studies on a gene-delivery system using granulocyte-macrophage colony-forming units (CFU-GM), a type of hematopoietic progenitor, we have established a technique for efficient gene transfer into CFU GM. DGL, a retrovirus vector containing the SV40 promoter and the neomycin resistance gene, was constructed and found to transfer genes effectively into murine CFU-GM, which subsequently expressed the neomycin resistance gene. After gene transfer of murine non-adherent bone marrow cells precultured in liquid culture with recombinant murine IL-3 (rmIL-3) and recombinant human IL-6 (rhIL-6) for 6 days, gene transferred CFU-GM in bone marrow cells were able to proliferate 5-10-fold and the ratio of gene transferred CFU-GM to total CFU-GM reached 70 100% from less than 1% in the liquid culture with rmIL-3, rhIL-6 and neomycin for 6 days. Using this protocol, we have been able to obtain large amounts of highly concentrated gene-transferred CFU-GM for fundamental research on CFU-GM gene delivery systems. PMID- 1880425 TI - Isolation of a 30 kDa immunoglobulin binding protein from Pseudomonas maltophilia. AB - We have demonstrated that Pseudomonas maltophilia (ATCC No. 13637) possesses an exposed, immunologically accessible protein which binds to the Fc region of several species of immunoglobulins. Whole bacteria suspensions were incubated for 18 h with purified 125I-labelled antibodies with and without added non-labelled immunoglobulins. The suspensions were centrifuged for 30 min and the pellet containing bacteria was assessed for radioactivity. Using this crude assay, the whole organism bound 125I-labelled rabbit and mouse immunoglobulins and the purified Fc portion of human IgG. All of these labelled preparations were competitively displaced by unlabelled rabbit and mouse immunoglobulins, and Fc of human IgG, as well as human immunoglobulin subclasses. The organism was sonicated to solubilize this immunoglobulin binding protein. Using this sonicated preparation, it was shown that unlabelled Fc of IgG, unlabelled mouse and rabbit immunoglobulins, all competitively displaced 125I-labelled human Fc of IgG in a dose-response manner. A partially purified protein was prepared by Sephacryl S 300 followed by Sephadex G-100 column chromatography. This preparation was incubated with 125I-Fc gamma and with the following purified unlabelled preparations: F(ab')2 of IgG, Fc of IgG, murine monoclonal IgA, IgG1, IgG2, IgG3, and IgG4. All except F(ab')2 of IgG produced dose response competitive displacement. The molecular weight, as estimated by SDS-PAGE and Western blot, was 30,000 daltons. In Western blots, Fc gamma, murine monoclonal IgA, and human immunoglobulin subclasses, all showed affinity for the immobilized protein. Human F(ab')2 fragments did not show affinity for the protein. Radioiodinated pseudomonal Ig-binding protein showed affinity for human IgG coupled to Sepharose, and was displaced by unlabelled pseudomonal Ig-binding protein. Scatchard analysis of binding showed two binding affinities: two distinct types of Ig-binding proteins were obtained, a high affinity with Kd = 1.54 x 10(-10) and a lower affinity with Kd = 2.36 x 10(-8). This immunoglobulin binding protein may be useful in immunoglobulin purification or identification. PMID- 1880426 TI - Measurement of affinity of viral monoclonal antibodies by ELISA titration of free antibody in equilibrium mixtures. AB - The binding affinity of a monoclonal antibody (Mab) to tobacco mosaic virus (TMV) was determined by measuring, in an enzyme-linked immunosorbent assay, the amount of free antibody present after ultracentrifugation of virus-antibody complexes at equilibrium. In antibody excess, univalent binding of Mabs was observed and the affinity constant was K = 3.2 +/- 0.4 10(8) l/mol; in antigen excess, bivalent antibody binding was observed and the antibody avidity was about 15 times higher. In antigen excess, it was imperative to correct experimental data for the presence of 0.55% inactive molecules in the immunopurified antibody preparation. Modelling studies suggest that in the case of antibodies of increasing affinity, it becomes increasingly important to correct for the presence of inactive antibody in the binding assay. PMID- 1880427 TI - Purification and characterization of human immunoglobulin IgA1 and IgA2 isotypes from serum. AB - A method is described for the simultaneous purification of IgA1 and IgA2 from human serum. Ammonium sulphate precipitation, gel filtration and ion-exchange chromatography on DEAE-Sephacel yielded a partially purified IgA preparation which was separated quantitatively into IgA1 and IgA2 by affinity chromatography on jacalin-Sepharose. The IgA1 which bound to the jacalin was eluted with 0.8 M D galactose. The IgA1 preparation was apparently homogeneous by SDS-PAGE but contained a trace of C1-inhibitor and a second protein detected by immunoelectrophoresis. The IgA2 which did not bind to the jacalin was purified to apparent homogeneity by chromatography on columns of Protein G-Sepharose, Fastflow-S Sepharose and Superose 6. Typical yields were 95% and 58% for IgA1 and IgA2 respectively or 253 mg and 24 mg per 100 ml serum. The IgA1 and IgA2 were characterised by their reactivity with isotype specific monoclonal antibodies and sensitivity to bacterial proteinases. The IgA2 preparation apparently contained both allotypes, IgA2m(1) and IgA2m(2). PMID- 1880428 TI - Isolation of human complement subcomponents C1r and C1s in their unactivated, proenzyme forms. AB - We have modified a standard isolation procedure for C1r and C1s, which employs IgG-Sepharose affinity chromatography followed by DEAE chromatography. As usual, all steps were performed at low temperature and two proteolytic inhibitors, PMSF and NPGB, were added during affinity chromatography on IgG-Sepharose. The novel condition was to keep the pH at pH 6.1 during the entire procedure, where activation was markedly depressed. In addition, purification was improved by washing the IgG-Sepharose column with a buffer free of added divalent cations immediately prior to elution of the C1r and C1s with EDTA. The final yields of highly purified C1r and C1s were about 20%; little or no activated material was detected in these highly purified fractions. PMID- 1880429 TI - Construction of representative immunoglobulin variable region cDNA libraries from human peripheral blood lymphocytes without in vitro stimulation. AB - We have developed a sensitive and specific method for preparation of representative IgM and IgG cDNA libraries of peripheral blood lymphocytes without in vitro stimulation of B cells and without primer-based bias. The procedure involves preparation of double-stranded cDNA from initial C mu and C gamma constant region primers. Linkers are attached to the cDNA and nonselective polymerase chain reaction (PCR) amplification is performed with the linkers as primers. This product is ligated to M13 RF DNA, and selective PCR amplification is achieved with a nested constant region primer and a vector primer. The product is cloned into M13 phage. More than 85% of the white plaques are positive with a JH probe. Diversity of the library is confirmed by hybridization with VH gene probes and by DNA sequencing. A sample of 7-30 ml of blood from a normal human adult can yield both mu and gamma cDNA libraries. Analysis of the libraries yields a picture of Ig variable gene usage at the time of sampling. PMID- 1880430 TI - An appraisal of polystyrene-(ELISA) and nitrocellulose-based (ELIFA) enzyme immunoassay systems using monoclonal antibodies reactive toward antigenically distinct forms of human C-reactive protein. AB - The purpose of this study was to compare and contrast two enzyme immunoassay systems: the enzyme-linked immunosorbent assay (ELISA), which utilizes polystyrene microtiter plates as the adsorptive surface and the enzyme-linked immunoflow assay (ELIFA), which utilizes nitrocellulose membranes. The principal parameter under scrutiny was the denaturing or unfolding effects caused by the interaction of the protein with the adsorptive surfaces in each assay system. These effects were monitored by utilizing two conformationally distinct forms of human C-reactive protein (CRP), the native form of CRP and a denatured form (M CRP), with a corresponding panel of monoclonal antibodies (MAbs) specific to either CRP or M-CRP. The results show that the ELIFA system was less sensitive than the ELISA system but that the ELIFA assay can be completed in less time than the ELISA. Also, adsorption of native CRP to the polystyrene surface in the ELISA system resulted in conformational changes of the adsorbed native CRP protein such that M-CRP reactive determinants were available for binding with anti-M-CRP MAbs, whereas native CRP adsorbed to the nitrocellulose membrane in the ELIFA system resulted in very limited conversion of CRP to M-CRP reactive epitopes. These results have important implications for development of immunoassays and screening of MAbs for proteins whose conformations may be affected by adsorption to various surfaces. PMID- 1880431 TI - A sensitive and efficient induction system for murine IgE. Single cell analysis at the clonal level. AB - A culture system is described which permits the analysis of IgE expression by single murine cells within clones of B cells. The system is based on the use of a CB5.1 stroma cell line as a feeder which optimally supports the IL-4-induced switch to IgE of LPS-stimulated B cells in culture. In this system 100 U/ml IL-4 induces the switch to IgE, in 3-5% of B cells and the switch frequency to IgG1 was as high as 2%. Five ng IgE or 12 ng IgG1 were produced per clone containing on average 13-15 PFC. The detection of single IgE secreting B cells was possible due to two newly developed, highly specific rat anti-mouse IgE antibodies used in a sandwich-ELISA. The frequency of IgE-secreting B cells was enhanced 2.5 times when the fibroblastoid CB5.1 cells rather than thymocytes were used as feeder cells. CB5.1 cells supported the differentiation of B cells to IgM-PFC almost as well as rat thymocytes (which have, to date, been used as the standard feeder layer) whereas the amount of secreted IgG1 was about 3 times lower than in thymocyte cultures. Optimal switching to IgE occurred at concentrations of IL-4 which were 10-fold lower than that required for IgG1 expression, a situation quite opposite to that observed in the rat thymocyte-supported culture system. In confirmation of established data the switch of B cells to IgE or IgG1 occurred randomly. The advantages of CB5.1 cells as feeder cells are (1) the use of a homogeneous and defined cell line, (2) their limited release of defined lymphokines (IL-6 and GM-CSF), and (3) the low degradation and consumption of cytokine factors. The combination of the CB5.1 cell line with a highly specific IgE ELISA assay made it possible to analyse the appearance of IgE producing cells within a developing B cell clone. PMID- 1880432 TI - A rapid method to determine the isotype and specificity of coproantibodies in mice infected with Trichinella or fed cholera toxin. AB - A method was developed to isolate and test coproantibodies from mice infected with Trichinella or mice fed cholera toxin. It was rapid as results were obtained within 3 h, and it was applicable to a single faecal pellet. It reduced the number of experimental animals required 7-fold, and reduced variability, since samples were obtained from the same experimental animal over time. As it was noninvasive, it did not alter normal gut physiology, nor the course of the parasitic infection. The immune response was monitored over time in individual mice, and specific sIgA and IgG isotypes were detected for both Trichinella and cholera toxin by ELISA. PMID- 1880433 TI - Evaluation of a closed perfusion chamber for single cell fluorescence measurements. PMID- 1880434 TI - Year of girl child. PMID- 1880436 TI - Addiction fear increasing among nurses. PMID- 1880435 TI - Endoscopic surgery in its latest relevance. PMID- 1880437 TI - Symptoms of pancreatic cancer. AB - We describe the symptoms, physical findings, treatment interventions, risk factors, and length of survival in persons with pancreatic cancer referred to a palliative care service (PCS) in a tertiary care facility. Data were collected prospectively over a 2-yr period using a standard clinical assessment tool in 39 patients with unresectable pancreatic cancer. Common symptoms include pain (82%), anorexia (64%), early satiety (62%), xerostomia and sleep problems (both 54%), and weight loss (51%). Analyzed retrospectively, 82% had at least one known risk factor for the development of pancreatic cancer. Twenty-five people presented to the PCS within 1 mo of diagnosis; in this group, length of survival was analyzed according to the presence of specific symptoms, and a significant inverse relationship between the presence of dyspnea and length of survival was found. As there is no effective treatment for surgically unresectable pancreatic cancer, palliation of common symptoms should be the primary emphasis of therapy. PMID- 1880438 TI - Piriformis muscle syndrome: an underdiagnosed cause of sciatica. AB - This is a retrospective review of 26 patients with sciatica due to the piriformis muscle syndrome. Most patients had pain in the buttock area and sciatica, and most experienced difficulty walking and sitting, even for short periods of time. Reproduction of the sciatica upon deep palpation, either by gluteal or rectal route, was diagnostic. Reproduction of sciatica occurred in 92% of the patients upon deep digital palpation and in 100% of the patients upon rectal or pelvic examination. Other signs were helpful but not consistent. After the appropriate diagnosis, the treatment was relatively easy and rewarding. This study emphasizes that the diagnosis of piriformis muscle syndrome is clinical; without the appropriate clinical examination, it can be easily misdiagnosed. PMID- 1880439 TI - Transdermal scopolamine use in the control of narcotic-induced nausea. AB - Nausea affects from 40% to 70% of cancer patients who received narcotics to manage their pain. This occurs more frequently when they are ambulatory than when they are recumbent and may be the result of narcotic-enhanced labyrinthine sensitivity to motion. Scopolamine has previously been found to be an effective antiemetic for motion sickness. In a prospective pilot study, 9 (69%) of 13 cancer patients experienced rapid relief of their narcotic-induced nausea when they used Scopolamine Transderm-V patches alone. Only two patients experienced side effects with the scopolamine, and in one patient, the side effects may have been dose related. Although tolerance to the increased vestibular sensitivity may occur, this was not universal. Further prospective trials are necessary to establish whether transdermal scopolamine is useful in controlling the narcotic induced nausea experienced by cancer patients. PMID- 1880440 TI - [Studies on 15 seropositive cases to Lyme disease using immunoperoxidase test in Japan]. AB - The serological survey, analyzing sera which were obtained from Lyme disease suspected subjects was performed using immunoperoxidase (IP) test between July, 1987 and February, 1989. Fifteen seropositive subjects to Borrelia burgdorferi have been found in this survey, and these cases were considered to be true Lyme disease or highly suspected for this illness. Most of these seropositive cases geographically occurred in northern part of Japan, and both sexes and all age subjects were affected. In clinical manifestations, 5 cases developed a typical skin lesion of erythema chronicum migrans (ECM) followed by tick-bite. Neurologic manifestations were found in 6 cases, including one patient who also had ECM after a known tick bite. Of these neurologic manifestations, 4 cases had lymphocytic meningitis, 3 unilateral or bilateral facial palsy, and one encephalomyelitis. When 8 of these 15 sera were analyzed for antibodies to Lyme disease with ELISA, a poor agreement of serodiagnosis between IP test and ELISA has been found in the course of this study. PMID- 1880441 TI - [Studies on the enteropathogenic mechanism of non-O1 Vibrio cholerae. I. Enteropathogenicity of clinical and environmental isolates]. AB - Enteropathogenicity and plasmid DNA of clinical and environmental isolates of non O1 V. cholerae were examined. Results were as follows: 1). The frequencies of enteropathogenic strains judged by the results from both ligated rabbit ileal loop (RIL) and suckling mouse tests were 36/38 (95%) for isolates from overseas travellers, 15/15 (100%) for isolates from food poisoning, 33/44 (75%) for isolates from fish and sea water, and 1/10 (10%) for isolates from river water. 2). Plasmid DNA was detected in eight of the 40 isolates examined, but the presence of plasmid did not correlate with enteropathogenicity. These results indicate that approximately three fourths of the strains isolated from fish and sea water are enteropathogenic, and that the genes controlling the enteropathogenicity of this organism probably exist in chromosomal DNA. PMID- 1880442 TI - [Enteroinvasive Escherichia coli O121: H- isolated from travellers' diarrhea]. AB - A lactose slow-fermenting, non motile Escherichia coli strain was isolated from a diarrheal patient returning from Indonesia. Examination of virulence of the strain showed that it penetrated into tissue culture cells, and were positive in Sereny test and enzyme-linked immunosorbent assay for detection of enteroinvasive E. coli. A large plasmid responsible for virulence was also detected. Thus the strain was confirmed to be a typical enteroinvasive E. coli. Analysis of O serotype using the antisera against E. coli O1-O170 revealed that the strain had O121 antigen, whose antiserum is not included in the commercial serotyping kit for the diagnosis of diarrheagenic E. coli. PMID- 1880443 TI - [Microbiological characterization of clinical isolates of Staphylococcus epidermidis]. AB - As a result of recent development in medical practice including use of new antimicrobial agents, coagulase-negative Staphylococci (CNS) that were once considered nonpathogenic contaminants have captured attention as causes of disease. The 43 clinical isolates of Staphylococcus epidermidis sensu stricto and 7 isolates of S. epidermidis from the medical staffs were characterized with regard to (1) their biochemical profiles, (2) slime productivity, (3) beta lactamase productivity and (4) plasmid patterns. Most of the isolates have an identical biochemical profile code. The slime production was observed in the 9 strains isolated from pleural effusions or the tubes used for pleural drainage. These strains had a similar antimicrobial susceptibility profile that are commonly seen in multi-resistant strains of methicillin-resistant Staphylococcus aureus (MRSA). In addition, most of these strains produced beta-lactamase. For the plasmid profiling, we selected 12 isolates that possessed 5 distinct antimicrobial susceptibility profiles. Upon agarose gel electrophoresis, 8 isolates were shown to possess a 1.9 kb plasmid. These 8 isolates had resistance against tobramycin (TOB) and erythromycin (EM). Emergence of S. epidermidis as causes of disease will increasingly necessitate the detailed microbiological characterization of the clinical isolates. PMID- 1880444 TI - [Effects of cefixime and cefaclor on pharyngeal flora in children]. AB - Influences of cefixime and cefaclor, oral antibiotics, were studied in 50 children (age range, 11 months to 13 years) with pharyngitis. Daily doses of cefixime were 6 to 10 mg/kg in 25 children and those of cefaclor were 40 to 50 mg/kg in 25 children. Pharyngeal swabs were taken before and after 3 to 7 days of the antibiotic treatment. Pathogenic organisms, such as Streptococcus pyogenes, Haemophilus influenzae and Streptococcus pneumoniae, were isolated in 14 children before and in 1 child after cefixime use. But these bacteria were isolated in 15 children before and in 9 children, and 3 strains of H. influenzae and 3 strains of S. pneumoniae were newly isolated after cefaclor use. An isolation rate of Gram-negative bacilli, such as Acinetobacter spp., were increased after use of cefixime. In both antibiotics, isolation rates of yeasts were slightly increased. An isolation rate of alpha-hemolytic streptococci was increased from 16% to 48% by cefixime treatment and from 24% to 52% by cefaclor treatment. The MIC50 of cefixime and cefaclor against alpha-hemolytic streptococci isolated after treatment was higher than that isolated before. Effects of cefixime and cefaclor was less extensive than that of ampicillin in previous reports. PMID- 1880445 TI - [Enzyme-linked immunosorbent assay using monoclonal antibodies for direct serotyping of enteric adenoviruses in feces]. AB - We were prepared three monoclonal antibodies in which the monoclone 12D was type specific for Adenovirus 40 (Ad40), 1F was type specific for Ad41 and 15D was group specific for Ads. For identification of enteric adenoviruses (EAd) in stool specimens, enzyme-linked immunosorbent assay (ELISA) test using monoclonal antibodies was developed. Results of identification by the ELISA tests using monoclonal antibodies to EAd on 15 fecal samples in which Ad particles were found by electron microscopy showed complete coincidence to those of Sma 1 restriction endonuclease cleavage. From these results, the ELISA tests employing EAds type specific monoclonal antibodies proved to be specific and this was a rapid technique for laboratory diagnosis of EAd in fecal specimens of viral gastroenteritis. Fifty-eight fecal samples with Ad particles positive by EM were serotyped by the ELISA using monoclonal antibodies. Eleven fecal samples were identified as Ad40, 25 as Ad41, 1 as double infection with Ad40 and Ad41, and 4 as non-EAd. These results indicated that Ad41 was more dominant than Ad40 during April, 1986 to January, 1989 in Matsuyama city. PMID- 1880446 TI - [T-serotype distribution of group A hemolytic streptococci in a rapidly expanding residential area in Sanda City, Hyogo Prefecture, with reference to an outbreak of serotype T-28 in autumn, 1988]. AB - In the fall of 1988, an outbreak of streptococcal infections was observed at 2 pediatric clinics in Sanda City, Hyogo prefecture. The 2 clinics were independent of each other; one (clinic A) was located in the down town area, in the older part of the city, where there is little population turn over, while the other (clinic B) was in a newly developed-fast growing residential district. The strains and the distribution of T-serotypes isolated at each location are as follows: clinic A; 58 strains (34.5% serotype T-4, 31.0% serotype T-12, 10.3% serotype T-1, and 23.3% serotype T-28), clinic B; 43 strains (48.8% serotype T 28, 23.3% serotype T-12, 11.6% serotype T-4 and 7.0% serotype T-1). According to the data from Kobe City infectious disease surveillance center, there were a total of 102 group A hemolytic streptococci strains isolated in 1988, the T serotypes distribution of which was as follows: 47.0% serotype T-4, 15.7% serotype the T-12, 10.8% serotype T-1 and 9.8% serotype T-28. Serotype T-4 was dominant here, as it was in location A of Sanda City. The epidemic proportion of serotype T-28 found at location B is considered to be due to the fact that location B has very little social interaction with location A and other areas. No difference was observed among the different serotypes on the drug susceptibility test: all strains showed a sensitivity to ampicillin and penicillin G, but were resistant to tetracycline and chloramphenicol. PMID- 1880447 TI - [Serum levels of healthy adult humans and changes of IgG subclass levels between infected and convalescent phase in respiratory infections]. AB - We measured serum levels of IgG subclasses in 100 healthy adult humans and 64 patients with respiratory infections by utilizing the enzyme linked immunosorbent assay (ELISA). The patients were composed of 18 patients with acute bacterial pneumonia and bacterial infection of 9 patients with pulmonary emphysema, 27 patients with chronic bronchitis and 10 patients with bronchiectasis. In healthy adults, serum levels of IgG1 subclass decreased in proportion of age increase. Serum levels of IgG2 rose after 30 years of age. Serum levels of IgG3 and IgG4 showed no remarkable changes by age. In patients with respiratory infectious disease, serum levels of IgG1, IgG2 and IgG4 decreased significantly but IgG3 increased significantly. We also measured serum levels of IgG subclasses in 10 patients with acute bacterial pneumonia and bacterial infection of 5 patients with pulmonary emphysema, 12 patients with chronic bronchitis and 4 patients with bronchiectasis at both infected and convalescent phases. The serum levels of IgG2 in patients with pneumonia and pulmonary emphysema at convalescent phase were significantly lower than those in the patients of infected phase. Other subclasses showed no significant change. We summarized that IgG2 was consumed at the infected phase by protecting against bacterial infections. IgG2 probably has an important role of protecting against bacterial respiratory infections among all IgG subclasses. PMID- 1880448 TI - Excretion of enterotoxin-producing Clostridium perfringens in feces by patients during and after diarrhea. AB - The excretion in the feces of Clostridium perfringens producing enterotoxin by 48 patients in 3 cases of food poisoning was studied during the illness and 1 and 3 months after the onset. Patients in the first outbreak excreted such strains mostly in the form of spores. In the second outbreak, spores and viable count cells were excreted in nearly equal numbers, and about 50% of the spores were enterotoxigenic. In the third outbreak, the strains were detected both as spores and as viable count cells during the illness. In all three groups, most fecal samples contained at least 10(3) spores per gram. About 1 month after the onset of the illness, (long after recovery from symptoms), 12 colonies producing enterotoxin were detected from five of the 22 samples of feces obtained from subjects in the three groups. There were few C. perfringens organisms, mostly spores, in the feces. Enterotoxin was not detected in the feces. About 3 months after onset, colonies producing enterotoxin could not be detected from feces of 11 of the subjects in the first group. We conclude that persons affected by C. perfringens food poisoning might contaminate food for at least 1 month after the onset. PMID- 1880449 TI - [Comparative studies on immunogenicity of Chinese hamster ovary cell derived HB vaccine and plasma derived HB vaccine]. AB - Chinese Hamster Ovary Cell derived HB vaccine (CDV) and plasma derived HB vaccine (PDV) were separately given to two groups of 131 and 112 medical stuff subjected, and both the anti-HBs responses were observed for 24 months from the time of first injection. The anti-HBs positive rate at the 7th month was 97% (mean geometric anti-HBs concentration 588 IU/L) in CDV group and 78% (83 IV/L) in PDV group, and the positive rate and mean titer of anti-HBs were always higher for 24 months in CDV group. The differences were remarkable between both the subjects aged over 40 years. The decreasing curves of the anti-HBs titer in the two groups were almost parallel; accordingly, the protective efficacy was estimated to be far longer in CDV. Also, the rate of non-responder was less lower (2.8%) in CDV group than that (15.2%) in PDV group. Above results show that CDV has a higher immunogenicity than PDV. PMID- 1880450 TI - Pseudomonas aeruginosa endocarditis in a patient with acute leukemia: probable etiologic role of central line-induced endocardial damage. PMID- 1880451 TI - [A study on hepatic dysfunction associated with rubella infection]. AB - We had 11 patients with rubella infection accompanied by hepatic dysfunction from 1979 through 1989. The elevations of sGOT were moderate, but sLDH levels were high. Extra hepatic manifestations were suspected by analysis of LDH isozymes. In 9 out of 11 patients, the sGPT levels returned to normal within 8 weeks. But prolonged courses of abnormal transaminase levels were observed in 2 patients. One was accompanied by underlying chronic hepatitis type non-A, non-B, and the other was supposed to have a prolonged rubella infection. Liver biopsy specimen taken from one patient in the acute phase demonstrated a non-specific reactive hepatitis. These observations suggest that rubella infection should be taken into consideration in making the diagnosis of sporadic hepatitis type non-A, non-B. PMID- 1880452 TI - [A case of postpartum fever caused by Mycoplasma hominis infection]. AB - A 26-year-old housewife was admitted to our hospital with a history of high fever after previous cesarean delivery. She had premature rupture of the membrane on the 41st week of pregnancy and the amniotic fluid was found to be cloudy on the fourth day after rupture. Therefore, cesarean delivery was performed. On the first day of operation, her body temperature increased up to 38 degrees C in spite of the treatment with Latamoxef (LMOX), 3 g/day. A sample of intrauterine material yielded M. hominis in pure culture. After administration of Minocycline (MINO) with antimycoplasmal activity, the clinical symptoms improved by the 11th day of operation. Sera obtained after the infection showed antibodies to M. hominis in ELISA study. These results suggested that the cause of this postpartum fever was M. hominis infection. PMID- 1880453 TI - Treatment of menorrhagia by radiofrequency heating. AB - A new technique is described for the treatment of menorrhagia by heating the whole of the endometrial cavity of the uterus. A capacitively coupled probe at 27.12 MHz is inserted into the uterine cavity, which causes the basilis layer to be raised to approximately 50-55 degrees C whilst the rest of the pelvic contents remain at approximately normal (body) temperature. A major advantage of the method is that no special hysteroscopic skills are required, unlike the two other techniques currently used for endometrial ablation: the Nd-Yag laser or the hysteroresectoscopic loop. Also no toxic flushing/distension fluids are necessary, as are required for all hysteroscopic surgery. The method, however, does require the application of a large amount of RF power to the probe and so care must be taken to position the probe correctly in order to prevent any serious complications. Of 32 patients given a single treatment at a power level of 550 W for 20 min, the 'success rate' was 84% with 31% becoming amenhorrhoiec and 53% showing significant reduction in menstrual bleeding. However, retreatment is possible and by this means, combined with improved treatment techniques, an even higher success rate could be achieved. In two of the earlier patients treated at 550 W a fistula was produced at the anterior vaginal wall which had to be surgically repaired. The probe was subsequently modified, since when this problem has not recurred. This new treatment approach offers an alternative to hysterectomy in the treatment of menorrhagia and may offer a number of significant advantages over methods currently used for endometrial ablation. PMID- 1880454 TI - Sensitization to hyperthermia by 3,3'-dipentyloxacarbocyanine iodide: a positive correlation with DNA damage and negative correlations with altered cell morphology, oxygen consumption inhibition, and reduced ATP levels. AB - The cyanine dye 3,3'-dipentyloxacarbocyanine iodide (DiOC5(3)) (concentrations of 0.5 microgram/ml to 5.0 micrograms/ml) was shown to be a potent sensitizer of Chinese hamster ovary (CHO) cells to hyperthermic cell killing at 43.0 degrees C or 45.5 degrees C, while exhibiting no cytotoxicity at 37.0 degrees C. Sensitization to hyperthermic cell killing was accompanied by an increase in damage to the DNA, as measured by DNA unwinding. The increased DNA damage correlated qualitatively with the enhanced heat killing induced by DiOC5(3). This correlation was better in cells heated at 43.0 degrees C than in those heated at 45.5 degrees C. DiOC5(3) is known to affect other cellular functions. It inhibits electron transport, uncouples oxidative phosphorylation, and inhibits calcium ATPases. The effects of DiOC5(3) on oxygen consumption and ATP content were therefore measured at 37.0 degrees C and at hyperthermic temperatures. The results demonstrated that inhibition of oxygen consumption and reduction of cellular ATP levels played no role in inducing heat sensitization in DiOC5(3) treated cells, or in causing cell death in cells treated with heat alone. PMID- 1880455 TI - Changes in hepatic blood flow during regional hyperthermia. AB - The influence of liver hyperthermia on hepatic arterial and portal venous blood flow to tumour and normal hepatic tissue was examined in a rabbit VX2 tumour model. Hyperthermia was delivered by 2450 MHz microwave generator to exteriorized livers in 18 rabbits. Blood flow was measured in both portal vein and hepatic artery using radioactive tracer microspheres before, during and 5 min after intense (greater than 43 degrees C) hyperthermia. During hyperthermia a decrease in total liver blood flow was composed primarily of a decrease in hepatic arterial blood flow to tumour tissue. Tumours were supplied almost exclusively by the hepatic artery and thus total tumour blood flow was significantly depressed during heating. The decreased tumour blood flow persisted after the cessation of hyperthermia and was indicative of vascular collapse in the tumour tissue. Temperature differentials in tumour compared to normal tissue ranged from 5 degrees C to 8 degrees C during hyperthermia because of the lower tumour blood flow. The portal vein exerted minimal influence on temperatures attained in the tumour tissue during hyperthermia but would have mediated normal liver tissue heat loss. PMID- 1880456 TI - Potential for localized, adjustable deep heating in soft-tissue environments with a 30-beam ultrasonic hyperthermia system. AB - Initial heating rates (degrees C/min) along parallel tracks at depths of 1-14 cm in a static, muscle-like phantom were determined from time-temperature profiles obtained with 'Helios', a 30-beam ultrasonic hyperthermia system developed by Varian Associates. Data were taken at a single operating frequency of 556 kHz, for different sets of focal plane ring diameters of the four-ring array applicator, different levels of transducer driving power and two different focal plane depths, 6 cm and 9 cm. In each experiment, at each point of temperature measurement, analysis of temperature versus time data over a 2 min heating interval permitted separation of the desired phantom heating from artefactual heating resulting primarily from absorption of transverse (shear) waves produced at phantom-metal probe catheter interfaces. The results of the studies conducted suggest that in a non-translating carriage mode, Helios can produce axially and laterally localized deep heating in soft tissues for tissue volumes of lateral dimension up to a minimum of 4 cm and tissue depths of at least 11 cm. The results obtained also suggest that Helios can produce laterally localized heating to tissue depths of at least 11 cm without excessive heating of superficial soft tissue layers, for tissue volumes of lateral dimension up to a minimum of 8 cm. The methodology used in the phantom studies was applied to the production of localized heating in the right lobe of the liver of adult pigs. Temperature versus time profiles obtained in the in vivo studies indicated that, for the set of system parameters employed, concentration of ultrasonic power at greater depths in the liver (e.g. 10.5 cm versus 5 cm) could be achieved, suggesting that Helios should be able to produce localized heating of targeted hepatic volumes when its operating parameters are selected in accordance with effective treatment planning techniques. PMID- 1880457 TI - Development of an inductive, non-invasive RF applicator for studying hyperthermia in a rat brain tumour model. AB - A non-invasive inductive RF applicator has been designed specially for local heating of 6 mm diameter tumours growing in the brains of F344 rats (144-148 MHz). It is shown that an inductive applicator is the choice for this particular case. The power deposition pattern is analysed by modelling the applicator with a three-dimensional array of magnetic dipoles. The total hyperthermia system is briefly described and results of phantom and in vivo experimental measurements are presented. These confirm the theoretical analysis. PMID- 1880458 TI - Optimal power deposition in hyperthermia. I. The treatment goal: the ideal temperature distribution: the role of large blood vessels. AB - Improved hyperthermia heating systems that have flexibility in their deposition patterns are becoming available commercially, and even more flexible systems are being developed in research laboratories. To best use these devices one must determine how to deposit the power optimally, for which one needs a clear thermal treatment goal including an ideal temperature distribution. This paper presents definitions for these quantities, and theoretically investigates the relative effects of thermal conduction and blood convection cooling on them. It is shown that both cooling mechanisms can be important clinically, and that the presence of 'large' blood vessels can have a major impact on the optimal power deposition patterns. In particular, an ideal heating system would deposit enough power both outside the treatment volume in order to preheat the incoming blood to the desired treatment temperature, and at the treatment volume boundary in order to overcome thermal conduction effects. The degree to which any heating system can approach the ideal temperature distribution is shown to be strongly influenced by the size and shape of its power deposition field, i.e. its conformability, or ability to conform to the boundary of the desired treatment volume. PMID- 1880459 TI - The effect of air cooling on the radial temperature distribution of a single microwave hyperthermia antenna in vivo. AB - Canine skeletal muscle was heated with a single microwave antenna within a brachytherapy catheter driven at 2000 MHz. The radial, steady-state temperature distribution was measured with and without air cooling of the antenna, as produced by room temperature air flowing in the catheter at 7.5 l/min. The axial temperature distribution was also measured with air cooling. In the antenna junction plane the area heated to a given temperature increased by a factor of four with air cooling when the same antenna temperature was enforced. With the same maximum temperature enforced, the area would increase by a factor of 2.5 with air cooling. The axial temperature distribution was not compromised by air cooling. PMID- 1880460 TI - Visualization by a matrix of light-emitting diodes of interference effects from a radiative four-applicator hyperthermia system. AB - A simple, unique tool has been constructed at a very low cost for visualization of the electric field distribution in a phantom exposed to radiofrequency fields from a four-applicator hyperthermia system. The tool consists of a thin Perspex plate to which light-emitting diodes (LEDs) have been attached in a regular pattern. The leads of these LEDs have been bent in the form of dipoles. Electric field distributions can be made visible, because the light intensity from an individual LED dipole in a RF field is a function of the local electric field strength. The LED dipoles were arranged in a 11 x 15 matrix with a mutual distance of 2 cm. Experiments have been performed in a cylinder with a length of 100 cm and with an elliptical cross-section of 24 cm x 36 cm. The cylinder was filled with saline to simulate the electric properties of biological tissue. The matrix plate was shaped like the cross-section inside the phantom, and could be moved to any position under the externally applied antennae. In our department the applicators installed form a system of four coherent waveguide radiators operating at a frequency of 70 MHz. Photographs have been taken from the distribution of the light intensity through transparent windows at the outer ends of the phantom. The advantage of the LED matrix is the fact that the effect of changing phase relations, amplitudes or position of any applicator on the electric field distribution can be seen instantaneously. The interference effects of multiple fields, i.e. extinction and reinforcement, become easily visible. Typical examples demonstrate the necessity to obtain the field distribution not only along some previously chosen lines, but in the whole transversal midplane. The attenuation of field strength due to the presence of the matrix varies only slightly from the edge to the centre of the matrix, so the pattern of light intensity is in good qualitative agreement with the pattern of field strength. The LED matrix has been very useful in the verification of pretreatment planning calculations, and is already used for intercomparison and evaluation studies of similar hyperthermia equipment. PMID- 1880461 TI - Flow dependence of 2-D temperature distributions induced in the perfused canine kidney by ultrasound. AB - The influence of perfusate flow rate on the two-dimensional (2-D) temperature distributions induced by hyperthermia in the canine kidney was evaluated. Localized hyperthermia was induced by ultrasound (frequency 2.040 MHz, transducer diameter 6.7 cm) in the ex-vivo perfused kidney. Temperatures were mapped using shielded copper/constantan thermocouple sensors. The 2-D temperature distribution of the kidney was obtained by pulling these sensors through a planar array of eight stainless-steel trocars inserted along its longitudinal axis. The perfusion system allowed for the control of internal/external organ temperature and type of perfusate, and it simulated vasodilation and vasoconstriction by changing the arterial volume flow rate. The temperature data obtained at flow rates ranging from 0 to 570 ml/min and power levels from 0 to 150 W showed that acoustic power densities in excess of 1.5 W/cm2 were required to maintain therapeutic temperatures in this system. Contour maps for characterizing the 2-D temperature distributions induced in this system were analysed with the introduction of a quantitative measure based on the area within a given isotherm. They show the effects of tissue heterogeneity, flow rate, and non-uniform power deposition. Time constants computed from the exponentially decaying temperatures measured following power off ranged from 5 to 555 s. These findings provide a basis for comparison with temperature measurements being acquired in the in-vivo kidney system. Information acquired from this system may facilitate the process of developing tissue-equivalent dynamic phantoms for ultrasound-induced hyperthermia. The ex-vivo model presented in this paper might be used to study the performance of alternative heating applicators, the effect of haematocrit, blood viscosity, and the use of vasoactive drugs. PMID- 1880462 TI - Attempt to induce total-body hyperthermia by whole-abdominal hyperthermia using a radiofrequency capacitive-heating system: an experimental study in dogs. AB - The effects of whole-abdominal hyperthermia (WAH), using an 8 MHz radiofrequency capacitive-heating system, on the intraperitoneal and extraperitoneal distribution of heat and on the functions of visceral organs were studied. Eight female mongrel dogs were divided into two groups. Five were infused and three were not infused intraperitoneally with physiological saline. The mean increase in systemic temperature during WAH was 6.4 degrees C for the saline-infused group and 5.1 degrees C for the non-infused group. The systemic temperature reached 40 degrees C about 50 min after the start of heating in four of five animals in the saline-infused group; three of the four animals died, and in these the maximum temperature of the liver exceeded 43.5 degrees C. The infusion of saline into the peritoneal cavity may facilitate the elevation of systemic temperature. The effects on the liver of WAH were very marked, as analysed by biochemical and histological techniques. Visceral organs tolerated heating to less than 43 degrees C by WAH alone. It appears that elevation of the systemic temperature to 40.5 degrees C or more can be safely achieved under conditions where the temperature in the peritoneal cavity is kept below 43.5 degrees C during WAH. PMID- 1880463 TI - Hyperthermia of pet animal tumours with self-regulating ferromagnetic thermoseeds. PMID- 1880464 TI - Conceptual issues in nursing ethics research. AB - Empirical studies that have attempted to describe nurses' ethical practice have used conceptual frameworks derived primarily from the disciplines of bioethics and psychology. These frameworks have not incorporated important concepts developed by nursing theorists over the past two decades. This article points out flaws in the past research frameworks and proposes a synthesis of ethical theory, nursing practice contexts, and empirical research methods to enrich theoretical development in nursing ethics. PMID- 1880465 TI - Separating care and cure: an analysis of historical and contemporary images of nursing and medicine. AB - This paper provides a philosophical critique of professional stereotypes in medicine. In the course of this critique, we also offer a detailed analysis of the concept of care in health care. The paper first considers possible explanations for the traditional stereotype that caring is a province of nurses and women, while curing is an arena suited for physicians and men. It then dispels this stereotype and fine tunes the concept of care. A distinction between 'caring for' and 'caring about' is made, and concomitant notions of parentalism are elaborated. Finally, the paper illustrates, through the use of cases, diverse models of caring. Our discussion reveals the complexity of care and the alternative modes of caring in health care. PMID- 1880466 TI - Integrity and compromise in nursing ethics. AB - Nurses are often caught in the middle of what appear to be intractable moral conflicts. For such times, the function and limits of moral compromise need to be explored. Compromise is compatible with moral integrity if a number of conditions are met. Among these are the sharing of a moral language, mutual respect on the part of those who differ, acknowledgement of factual and moral complexities, and recognition of limits to compromise. Nurses are in a position uniquely suited to leadership in fostering an environment that makes compromise with integrity possible. PMID- 1880467 TI - Nursing responsibility for the placebo effect. AB - The placebo effect is a common phenomenon in therapy and research but has received very little attention as such in nursing research. This article reviews some of the literature which shows the placebo effect, which can be positive or negative, is a significant force. Then it is argued that, while all health professionals have a general obligation to benefit their patients, nursing has a special, specific obligation to enhance the placebo effect, to maximize a positive effect and minimize a negative effect. Nursing education, current policy statements, and circumstances of clinical practice explain this obligation. Nursing research is needed to clarify the multiple ways in which the social and physical environment can trigger a placebo effect. As nursing expands its knowledge of this effect, it can begin to educate patients to the self-care implications of this pervasive but misunderstood phenomenon. PMID- 1880469 TI - Endocrine physiology and the value of case studies. PMID- 1880468 TI - Common morality, virtue, and abortion. PMID- 1880470 TI - Steroidogenesis during postnatal development in the mouse ovary. AB - In the mouse, follicular formation and development is largely postnatal. Changes in ovarian steroidogenesis during early postnatal life are likely, therefore, to reflect changes in follicular activity during early folliculogenesis. In this study, basal progesterone and androstenedione production and responsiveness to gonadotrophins, dibutyryl cyclic AMP (dbcAMP) and 22R-hydroxycholesterol have been measured following short-term in-vitro incubations of ovaries from mice aged 1, 3, 5, 7, 10 or 15 days. On the day of birth (day 1), basal and gonadotrophin stimulated progesterone and androstenedione production were undetectable although a response to dbcAMP and a low level of cholesterol side-chain cleavage (CSCC) activity (measured using 22R-hydroxycholesterol) were present. On day 3 progesterone and androstenedione production were undetectable under all conditions. On day 5 only a low level of CSCC activity was detectable but on day 7 there was an increase in ovarian steroid production. Basal progesterone and androstenedione were detectable and LH, but not FSH, increased the production of both steroids. These changes were associated with a marked increase of more than 80-fold in CSCC activity. Basal steroid output increased from days 7 to 15 and LH continued to stimulate progesterone accumulation although no effect on androstenedione was seen. Addition of FSH had no effect on steroidogenesis on day 10 but significantly increased progesterone production on day 15. Ovaries from the mice used in these studies contained primordial follicles and stromal tissue on day 1. By day 5 primary and secondary follicles were present and the major increase in steroid production between days 5 and 7 was associated with an increase in secondary follicles and increased differentiation of the thecal tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880471 TI - Studies on the testicular source of inhibin and its route of secretion in rams: failure of the Leydig cell to secrete inhibin in response to a human chorionic gonadotrophin/LH stimulus. AB - To determine whether Leydig cells produce inhibin in the ram, Leydig cells were stimulated by administering human chorionic gonadotrophin (hCG) or raising the levels of endogenous LH by an injection of gonadotrophin releasing hormone (GnRH). Plasma concentrations of testosterone increased in the 72 h after either a single injection (P less than 0.05) or two injections (P less than 0.01) of hCG. Plasma concentrations of inhibin were not significantly influenced by either one or two injections of hCG. Administration of GnRH (1 microgram) caused an 11 fold increase in plasma concentrations of LH but did not influence concentrations of inhibin in either the jugular or testicular veins (pampiniform plexus). In contrast, concentrations of testosterone were increased by about fourfold in both jugular (P less than 0.01) and testicular (P less than 0.05) veins. The concentrations of inhibin in the testicular vein were 1.3-fold higher than in the peripheral plasma (P less than 0.05) both before and following treatment with GnRH whereas the concentrations of testosterone were 18- to 21-fold greater than in peripheral concentrations. In view of the difference in concentrations of inhibin between testicular and jugular veins, in a further experiment a sample was taken from the jugular vein, a vein located in the tunica vasculosa of the testis (testicular vein) and from a vein (spermatic vein) and lymph vessels located in the spermatic cord. The mean (+/- S.E.M.) concentrations of inhibin were highest in the testicular lymph (45.93 +/- 4.21 micrograms/l; P less than 0.001) compared with the peripheral (4.14 +/- 0.31 micrograms/l), spermatic (8.0 +/- 1.17 micrograms/l) or testicular (6.4 +/- 0.82 micrograms/l) plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880472 TI - Stimulation of body weight gain of the mature female rat by bovine GH and bovine placental lactogen. AB - Mature female rats (200 g) were treated for 10 days with either recombinant bovine GH (bGH) or recombinant bovine placental lactogen (bPL) to compare the somatogenic responses elicited by these hormones. The treatments were administered by daily s.c. injection at four dose levels (0.19, 0.56, 1.67 and 5.0 mg/day). Both bGH and bPL stimulated significant increases in weight gain, but the slopes of the dose-response curves were different (P less than 0.05). Bovine PL was more potent than bGH (P less than 0.01) at the lowest dose, although there were no differences between treatment groups at the three higher doses. Feed consumption was stimulated more by bPL than bGH at all doses (P less than 0.001). The concentration of insulin-like growth factor-I (IGF-I) in blood plasma was increased by bGH in a dose-responsive manner and was higher than control at doses of 1.67 and 5 mg/day (P less than 0.05). Low doses of bPL stimulated increases in IGF-I similar to those with bGH. At the highest dose of bPL, however, there was no concomitant increase in plasma IGF-I. Nevertheless, the growth rate of the animals in this group matched that of the group given the highest dose of bGH. Receptor binding studies indicated that bPL bound to both GH and prolactin receptors. This is consistent with the growth data which suggests that bPL stimulated weight gain through a somatogenic mechanism as well as by another route, possibly mediated by lactogenic receptors. PMID- 1880473 TI - Identification of circulating growth hormone-binding proteins in domestic poultry: an initial characterization. AB - Multiple growth hormone (GH)-binding proteins (GHBPs) were identified in serum and plasma samples from domestic chickens and turkeys. Proteins were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis on 10% acrylamide, 2.7% bis discontinuous gels under reducing conditions and electrotransferred to nitrocellulose paper. Western blots were incubated with 125I-labelled recombinant chicken GH (cGH) or bovine GH and GHBPs visualized by means of autoradiography. In fresh samples (less than 2 h from collection to gel electrophoresis), multiple minor high Mr bands were evident between approximately 72,000 and 175,000. Two major bands were observed at approximately 69,500 and 27,500. The latter is consistent with previous reports for the rat and mouse serum GHBPs based on nucleotide sequence analysis. The minor bands were essentially undetectable after storage at -25 degrees C for several months, and an additional major band at Mr approximately 52,500 appeared. The Mr-69,500 major protein contained N-linked carbohydrate, as determined by a reduction in molecular size by treatment with peptide N-glycosidase F. Binding of 125I-labelled GH was partially inhibited by co-incubation with 50 micrograms unlabelled pituitary-derived cGH/ml and excess unlabelled porcine GH as well as ovine prolactin, but not by bovine insulin. Non specific binding of 125I-labelled GH by serum albumin was also observed. A comparison was made between these GHBPs and the hepatic GH receptor (e.g. molecular weight estimates, affinity for homologous versus heterologous GHs, cross-reactivity with prolactin, presence of N-linked carbohydrate). The origin and relationship among the various molecular weight species of GHBPs identified, and their potential role in regulation of the biological activity of GH in birds, remain to be determined. PMID- 1880474 TI - A decline in prolactin levels in amniotic fluid and decidua at term pregnancy after the initiation of labour. AB - Prolactin is known to inhibit the production of prostaglandins, key substances in the initiation of labour. To explore a possible role of prolactin in human parturition, prolactin levels were therefore measured in amniotic fluid and decidua at full-term pregnancy. Prolactin levels in amniotic fluid before labour were about three times higher than those at labour and they tended to decrease with time during labour. Prolactin levels in decidua before labour were about twice as high as those at labour. These findings suggest a possible involvement of prolactin in human parturition. PMID- 1880475 TI - Do in-vivo suppression and stimulation of lipolysis influence thyroid hormone levels in man? AB - To determine whether increases in non-esterified fatty acids alter free thyroid hormone and TSH levels, the effect of endogenous activation of lipolysis by insulin-induced hypoglycaemia was examined in seven healthy volunteers pretreated with placebo or acipimox. Whilst levels of non-esterified fatty acid were very different in the two groups, levels of free thyroxine, tri-iodothyronine and TSH were unchanged. Thus, within the range of non-esterified fatty acid levels likely to be seen in clinical practice, any effect on thyroid hormone measurements can be safely ignored. PMID- 1880476 TI - Insulin-like growth factor-I production and action in porcine thyroid follicular cells in monolayer: regulation by transforming growth factor-beta. AB - The regulation of thyroid follicular cell growth in vitro involves autocrine or paracrine actions of insulin-like growth factor-I (IGF-I), which are partially suppressed by transforming growth factor-beta (TGF-beta). Using subconfluent monolayers of porcine thyroid follicular cells, the aims of this study were to establish whether the actions of TGF-beta involve changes in the synthesis of, or response to, IGF-I. We also investigated the extent to which inhibitory actions of iodide on IGF-I-dependent proliferation of thyroid follicular cells may be attributable to the production of TGF-beta by follicular cells, as opposed to iodide-mediated autoregulation events. Exposure of porcine thyroid follicular cells in subconfluent monolayer culture to TGF-beta over a 7-day period reduced both IGF-I release and the incorporation of [methyl-3H]thymidine into trichloroacetic acid-precipitable cellular material, while preincubation of cells with NaI (0.1 mmol/l) for 24 h prior to the addition of TSH reduced the stimulatory effect of the latter on IGF-I release over the following 7 days. Preincubation of cells with iodide also reduced basal (i.e. autonomous) [methyl 3H]thymidine incorporation. This effect was partially reversed when, following initial exposure to follicular cells, iodide-containing preincubation medium was immunoadsorbed with a neutralizing TGF-beta antiserum, and subsequently re-added to the cells. Furthermore, similar immunoadsorption of iodide-free preincubation medium resulted in an enhancement of the control level of [methyl-3H]thymidine incorporation when the treated medium was returned to the original cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880477 TI - Binding and bioactivity of ovine and porcine prolactins in porcine mammary tissue. AB - Differential binding of homologous and heterologous prolactin was investigated in porcine mammary tissue. Specific binding of ovine prolactin to porcine mammary membranes or tissue slices was significantly greater than specific binding of the homologous porcine prolactin. Ovine prolactin was also more potent than porcine prolactin in stimulating proliferation of Nb2 cells. In contrast, stimulation of glucose metabolism in porcine mammary explants by porcine prolactin was greater than that by ovine prolactin. Differences in specific binding were probably not due to damage during iodination, as low concentrations of iodinated prolactins were similar to unlabelled prolactins in their abilities to stimulate proliferation of Nb2 cells. Furthermore, electrophoretic analysis of medium from binding reactions suggested that differences in specific binding were not due to proteolytic cleavage of the homologous prolactin into large (greater than 10 kDa) fragments. These studies suggest that ovine prolactin either binds to sites in addition to the authentic lactogenic receptor in porcine mammary tissue or that a significantly higher affinity of ovine prolactin for the porcine lactogenic receptor has little effect on its biological activity. PMID- 1880478 TI - Influence of protein nutrition on the response of growing lambs to exogenous bovine growth hormone. AB - Interactions between protein supply and the anabolic response to exogenous bovine (b) GH have been examined in two experiments using 28-35 kg lambs sustained entirely by intragastric infusion of volatile fatty acids (700 kJ/kg W 0.75 per day) into the rumen and the casein (600 mg (low protein; LP) or 1200 mg (high protein; HP)/kg W 0.75 per day) into the abomasum. Sheep received continuous i.v. infusions of bGH for 6 days in experiment 1 and for 18 days in experiment 2. Nitrogen balances were determined daily throughout both experiments and blood samples, from indwelling catheters, were assayed for GH, insulin-like growth factor-I (IGF-I), insulin and glucose. Infusion of bGH increased plasma GH concentration by five- to sixfold in all animals. There was an increase in N retention in both HP and LP animals over the first 2-3 days of GH administration. HP animals sustained higher N retentions (31%; P less than 0.05) throughout the GH administration but LP animals did not. In contrast, plasma IGF-I concentrations increased progressively over the first 72 to 96 h of GH administration in all sheep and thereafter remained significantly (P less than 0.05) elevated until termination of the GH infusion. In lambs which received both HP and LP infusion in experiment 1 the increase in IGF-I and LP infusions in experiment 1 the increase in IGF-I concentration by day 6 of GH administration was significantly (P less than 0.05) greater when they received the higher protein intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880479 TI - Osmoregulatory actions of insulin-like growth factor-I in rainbow trout (Oncorhynchus mykiss). AB - The ability of insulin-like growth factor-I (IGF-I), insulin and GH to promote hypoosmoregulatory ability was examined in juvenile rainbow trout (Oncorhynchus mykiss). Following adaptation to 12 parts per thousand (p.p.t.) seawater for 5 days, fish were given a single injection of hormone or vehicle, then exposed to 29 p.p.t. for 24 h and examined for changes in plasma osmolarity, ions and glucose. Ovine GH (oGH; 0.2 micrograms/g) significantly improved the ability of rainbow trout to maintain plasma osmolarity and sodium levels following transfer to 29 p.p.t. seawater. Recombinant bovine IGF-I (0.01, 0.05 and 0.02 micrograms/g) also improved the hypoosmoregulatory ability of trout; the effect being dose-dependent and greater than that of oGH. Bovine insulin (0.01, 0.05 and 0.2 micrograms/g) had no statistically significant effect on plasma ions. The results indicate that IGF-I is a potential mediator of the action of GH in seawater adaptation of salmonids. PMID- 1880480 TI - Whatever happened to Medicare reimbursement reform? PMID- 1880481 TI - Physician attitudes and behavior in response to changes in Medicare reimbursement policies. AB - BACKGROUND: Rapidly changing Medicare reimbursement policies since 1983 have affected every primary care physician. This study has attempted to quantify the attitudes and behaviors of Ohio primary care physicians toward these changes. METHODS: In Ohio, 1758 primary care physicians were surveyed by a mailed questionnaire about their attitudes toward recent changes in Medicare reimbursement policies and the resulting changes in their practices. RESULTS: More than 80% of respondents termed most Medicare policies as "objectionable" or "very objectionable." Fifty percent were limiting the number of Medicare patients in their practices. Family physicians and physicians who perceived their income to have decreased and their staff workload to have increased were also more likely to limit the number of Medicare patients in their practices. CONCLUSIONS: Ohio primary care physicians have a negative opinion of Medicare reimbursement policies and have limited their practices significantly as a result. PMID- 1880482 TI - A clinical trial of the American Heart Association step one diet for treatment of hypercholesterolemia. AB - BACKGROUND: Although diet therapy is the primary treatment for hypercholesterolemia, a trial to determine the effectiveness of the new American Heart Association Step One Diet (AHA diet) in lowering cholesterol has to our knowledge never been carried out. METHODS: A clinical trial was conducted to assess the plasma lipids response and adherence to the AHA diet in 120 men and women with hypercholesterolemia. All subjects were advised to follow the AHA diet for 18 weeks. RESULTS: After 6 weeks of the AHA diet intervention, there were modest but significant reductions in plasma total cholesterol (-2.6%) and low density lipoprotein (LDL) cholesterol (-3.5%), but no further significant reductions were observed thereafter. Rather, there was a tendency to return to and even exceed baseline levels of total cholesterol and LDL cholesterol over the subsequent 12 weeks, in spite of the subjects' reported continued adherence to the AHA diet and maintenance of weight loss throughout the entire study period. Nevertheless, 51% of the subjects had experienced improvement (-0.2% to -26.3%) in their plasma LDL cholesterol levels by the end of the study. CONCLUSIONS: A probable reason for the limited response of the diet was low baseline levels in intake of saturated fat and cholesterol by participants. The subjects who were older and had higher levels of plasma LDL cholesterol and total fat intake at baseline experienced better plasma LDL cholesterol response to the AHA diet. Thus, practicing physicians should consider assessing the baseline dietary fat and cholesterol intake of patients with hypercholesterolemia before starting the AHA diet, since patients may already be following a relatively prudent self selected diet. Additional dietary gains in lipid management might well require a more severe restriction of dietary fats and cholesterol. Long-term efficacy of the AHA diet should also be evaluated clinically with periodic lipid profiles. PMID- 1880483 TI - Recognition of depression in patients who smoke. AB - BACKGROUND: Depression is a common illness in family practice and is frequently missed by busy practitioners. Recent studies have suggested a relationship between smoking and depression in the general population. The purpose of this study is to determine whether a patient's smoking is related to the physician's recognition of a patient's depression. If so, smoking may serve as a cue used by physicians to recognize depression in their clinical decision-making process. METHODS: Adult patients presenting to the University of Oklahoma Family Practice Residency Clinic were screened for depression using the short form of the Beck Depression Inventory (BDI). After each patient visit, upper level residents or fellows completed response cards on which they recorded their assessment of the likelihood of a depression, their familiarity with the patient, and whether they had any knowledge of a depression history. RESULTS: The prevalence of depression as measured by the BDI among smokers (n = 232) and nonsmokers (n = 472) was 24.1% and 15.3%, respectively, a significant difference (P less than .001). Physicians identified depression at a significantly higher rate (75.0%) among depressed smokers than among depressed nonsmokers (48.6%) (P less than .0001). Smokers were 2.06 times as likely to be labeled depressed when controlling for the presence of a current depression, physician knowledge of a depression history, and physician familiarity with the patient (P less than .0001, 95% CI = 1.44,2.94). CONCLUSIONS: Smoking may serve as a cue for the clinician in the recognition of depression. Further research is needed to determine how smoking or a related factor may be used by physicians to correctly identify depression. PMID- 1880484 TI - Serum cholesterol: attitudes and behavior of family practice residents. AB - BACKGROUND: Given the current health promotion efforts regarding coronary artery disease, more information is needed about residents' attitudes and behaviors that relate to identification and management of patients with elevated serum cholesterol levels. METHODS: Family practice residents from eight US programs (N = 128) were surveyed in 1989 to assess their attitudes and reported practice patterns. Resident survey data were compared, when feasible, to published data from 1986 and 1990 surveys of practicing physicians performed by the National Heart, Lung, and Blood Institute. RESULTS: The use of faculty "key contacts" resulted in a 90% response rate (N = 115). Both residents and practicing physicians attributed a high degree of importance to cholesterol as a risk factor. Residents reported more frequent routine screening of middle-aged men than the routine screening rate of practicing physicians in 1986 (P less than .01). Residents reported less frequent screening of younger and older adults than of middle-aged men (P less than .001). Residents' threshold for the use of cholesterol-lowering medication was lower than that of practicing physicians surveyed in 1986, but higher than that of physicians surveyed in 1990. Compared with practicing physicians, residents did not believe they were as well prepared to counsel patients about dietary change or as successful when they tried to help patients make changes; residents reported a significantly higher rate of referral to dietitians (P less than .01). CONCLUSIONS: Residents may need more education regarding screening guidelines for children and young adults. A health promotion skills gap may exist that explains reported discrepancies between self-report and actual behavior and indicates that residency educators may need to pay more attention to fostering dietary assessment and counseling skills in their residents. PMID- 1880485 TI - An evaluation of a whole blood prothrombin analyzer designed for use by individuals without formal laboratory training. AB - BACKGROUND: The prothrombin time (PT) test, which is the most common coagulation test used in the outpatient setting, has not been recommended for office laboratory use because it has been technically difficult to perform. Consequently, serious errors in patient care could occur because of an erroneous result. The Coumatrak (E.I. Du Pont, Wilmington, Del) now allows nontechnically trained office staff to perform PT tests using a fresh capillary whole blood sample, individually packaged reagent cartridges, and a portable battery-operated instrument. METHODS: Coumatrak PT testing was compared with standard methods for both precision and accuracy, using protocols developed by the National Committee for Clinical Laboratory Standards (NCCLS). Reagent stability and operator variability were also studied. RESULTS: The results produced by a trained technologist and nontechnically trained staff were comparable. Test results obtained with the Coumatrak were approximately 10% higher than results obtained using standard laboratory equipment and methods using comparable blood samples from the same patients. It was found that the capillary blood specimen had to be rapidly transferred to the reagent cartridge in order to avoid factitiously low results. CONCLUSIONS: The Coumatrak can rapidly provide PT test results that are clinically useful for the office management of patients being treated with a warfarin anticoagulant and for the diagnosis of selected disorders. The system was found to be easy to operate, appropriate for use by individuals with little laboratory experience, and was subject to few operational problems during this study. PMID- 1880486 TI - Drug interactions software programs. AB - The value of a computer application is usually dependent on the program's ability to store, rearrange, and retrieve information in a format that is useful to the computer user. Based on a list of drugs (input), drug interactions programs search their databases for possible interactions between each drug pair in the input list. An output list specifies pairs of drugs that potentially interact. Since each program uses its own information database, results may differ slightly among programs. In general, however, the screen menus, appearance of the programs, and the "extras" included in each program differ more than the programs' drug interactions output. The software programs tested are all easy to use. Each of the three drug interactions programs reviewed has unique features that may appeal to certain users. The Medical Letter Drug Interactions Program is the least costly and provides the most academic output, allowing users to view citations for each specific interaction. The PDR Drug Interactions and Side Effects software includes a side effects index that allows either searching of a drug, which produces a list of the drug's side effects, or searching of a specific side effect, which produces a list of drugs associated with that side effect. Drug Interactions III is the only program that allows users to add drug interactions to its database. PMID- 1880487 TI - A critical review of labor and birth care. Obstetrical Interest Group of the North American Primary Care Research Group. AB - A critical review of the literature regarding important aspects of labor and delivery was conducted by members of the Obstetrical Interest Group of the North American Primary Care Research Group using computerized searches, personal communication, and literature exchange between group members. Each written topic summary was carefully reviewed by a second group member, and a consensus was reached regarding conclusions and recommendations by the group. The topics include family involvement, comfort measures, fetal heart rate monitoring, labor augmentation, birth positions, and episiotomies. Each topic summary is preceded by conclusions and recommendations given in the order of least invasive to most invasive of the woman in labor. The strength of these conclusions and recommendations is based on the amount and type of supportive data in the literature and is indicated by one to three stars preceding that statement. One star conclusions are not well supported in the literature but reflect a family practice style and were reached through consensus from the group. Three-star conclusions are supported by data from clinical trials. PMID- 1880488 TI - Reiter's syndrome and HIV infection. PMID- 1880489 TI - Conversion disorder in an adult incest survivor. PMID- 1880490 TI - Enalapril-induced immunologic impairment of hepatic function. PMID- 1880491 TI - Developing a patient education newsletter. PMID- 1880492 TI - Prozac and suicide. PMID- 1880493 TI - 'No narcotics' policy. PMID- 1880494 TI - Differential diagnosis of acute viral hepatitis using rapid, fully automated immunoassays. AB - We report the development of three rapid, fully automated immunoassays allowing the differential diagnosis of acute viral hepatitis. These assays detect HBsAg, IgM antibody to hepatitis B core antigen (IgM anti-HBc) and IgM antibody to hepatitis A virus (IgM anti-HAV) using the IMx instrument system. All IMx assays were run in less than 45 minutes and all steps were fully automated including specimen dilution steps. Specimens from blood donors, diagnostic and hospital patients, and individuals with a variety of infectious and immune diseases were tested for IgM anti-HAV (n = 1473) or for IgM anti-HBc (n = 1606) or for HBsAg (n = 9700) by the IMx and commercially available EIA and RIA. Each IMx assay showed 99.8% agreement with current EIA. Reproducibility in all hepatitis IMx assays was significantly better than that observed with manual or semiautomated assays; within-run and between-run % CV ranged from 2.2 to 4.8 and 3.5 to 10.3 respectively. In 29 acute hepatitis B patients studied, HBsAg and IgM anti-HBc were detected in the first available patient bleed collected from 0 to 4 week from the onset of symptoms. IgM anti-HBc persisted at reactive levels in the IMx assay for 1 to 24 weeks (mean 12.1 +/- 5.3 weeks) after the patient presented with symptoms. In individuals exposed to hepatitis A, IgM anti-HAV was detectable by IMx by 40 days post exposure (average 33.5 days) and IgM had declined to unreactive levels in IMx for all patients by from 3 to 6 months post exposure. These data demonstrate the use of these rapid IMx assays for differentiation of acute hepatitis A and B. PMID- 1880495 TI - Expression and characterization of the preS1 peptide of hepatitis B surface antigen in Escherichia coli. AB - The infectious particles of hepatitis B virus (HBV) contain 3 related surface antigens, i.e., small, medium, and large, all of which are encoded by one large open reading frame with multiple initiation codons. The large surface antigen (L Ag) contains preS1, preS2, and S regions while both the middle and small surface antigens lack preS1. Several lines of evidence suggested that the preS1 region is involved in the binding of HBV to human hepatocytes as shown by its binding to HepG2 cells and isolated human hepatocyte membranes. To obtain large quantity of preS1 peptide, an expression vector was constructed containing a lac promoter, the 5' half of the beta-galactosidase gene, the Factor Xa tetrapeptide recognition sequence, and the coding region of preS1 plus preS2. This recombinant plasmid constitutively produced high concentration of a fusion protein in inclusion bodies in Escherichia coli. When the fusion protein was treated with Factor Xa, a peptide consisting of the N-terminal 91 amino acids of the preS1 region was released. This preS1 fragment purified by anion exchange chromatography was able to bind specifically to the isolated plasma membranes from human liver. Hence, this recombinant preS1 peptide can be used to identify and isolate hepatocyte receptors for HBV. PMID- 1880496 TI - Measles virus specific antibody in infants in a highly vaccinated society. AB - Measles virus specific antibody levels were measured in infants from 2 to 12 months of age. The sera were tested by hemagglutination-inhibition (HI), neutralization (NT), and enzyme immunoassay (EIA) methods. The results of this study indicate that in the population examined, infants at an early age have very low or no immunity of maternal origin to measles virus-93% of the infants were without detectable neutralizing antibody (NT titer less than or equal to 10) at 6 months of age, and by the end of the first year of life 100% had no neutralizing antibody. PMID- 1880497 TI - Stability of molluscum contagiosum virus DNA among 184 patient isolates: evidence for variability of sequences in the terminal inverted repeats. AB - The stability of the Molluscum contagiosum virus Type 1 genome (188 kbp) was studied in 184 DNA isolates from 131 patients. Variability of up to 1.5 kbp at both ends of the genome symmetrically was observed using restriction analysis of the DNA isolates and by Southern Blot experiments using cloned and labeled HindIII terminal DNA fragments of MCV-1 prototype DNA. The variable sequences were mainly confined to the terminal fragments and parts of the MCV-1 terminal repeats. Labeled probes did not detect terminal sequences of MCV Type 2 under the applied stringency. A less marked instability of the central MCV-1 BamHI DNA fragment F was observed within the genome coordinates 0.431 to 0.454 mu. Reiteration of tandem repeats similar to those described for vaccinia virus might explain the variability of the terminal sequences and might be involved in viral replication. PMID- 1880498 TI - Inactivation of intestinal alkaline phosphatase by inositol hexaphosphate-Cu (II) coordinate complexes. AB - Alkaline phosphatase (APase) was greater than 99% inactivated upon incubation with myo-inositol hexakisphosphate (IHP) and Cu(II) ions. In the absence of Cu(II), IHP did not inactivate the enzyme. Likewise, cupric ions alone did not produce inactivation. Reactions of APase with IHP plus Cu(II) were competitively inhibited by zinc ions. In contrast to the marked effect of (IHP-Cu) chelate complexes on APase activity, the complexes of IHP with either Zn(II) or Mn(II) had no discernable effect. Both the extent and the rate of activity loss were dependent on the combined IHP and Cu(II) concentration. At an IHP to Cu(II) ratio of 11.6, the extent of inactivation was approximately proportional to the Cu(II) concentration with maximal inactivation attained above 10 microM. Under the same conditions, a nonlinear relation (saturation kinetics) was observed between the pseudo first-order rate constants for the reaction and the IHP and Cu(II) concentration. On the basis of adherence of the data to a mechanism involving an intermediate whose concentration was rate determining, it was suggested that a ternary complexes composed of the apoprotein, the catalytic site zinc ions, and one or more specific IHP-Cu(II) complex [( IHP-Cu]*) may be the first step along the reaction coordinate. Relevant to this possibility which assumes active site interaction is the fact that both IHP alone and (IHP-Cu) complexes are good competitive inhibitors of p-nitrophenyl phosphate hydrolysis under the same solution conditions wherein APase inactivation occurs in the absence of substrate. Rates of enzyme inactivation are decreased with an increase in pH from 6.5 to 8.0. They are also dependent upon buffer type and concentration, apparently related to their association constants for cupric ion binding. Over and above such specific effects, rates of inactivation are also reduced with an increase in ionic strength. Depending on the ratio and concentrations of IHP and Cu(II) used in the reaction with APase, subsequent exposure to EDTA followed by assay in the presence of Zn(II) gave recoveries of activity ranging from 60% to 100%. Both the prior inactivated enzyme (containing IHP and cupric ions) in the presence of EDTA and the native APase upon simultaneous exposure to IHP, Cu(II), and EDTA were slowly and irreversibly inactivated. Correction for this effect gave reconstitution of activity of the (IHP-Cu)-inactivated APase by Zn(II) addition equivalent to that which could be obtained by EDTA-treatment of the native enzyme.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1880499 TI - Reversible inhibition of intestinal alkaline phosphatase by inositol hexaphosphate and its Cu(II) coordinate complexes. AB - The influence of inositol hexakisphosphate (IHP) and its cupric ion chelate complexes on alkaline phosphatase (APase) catalysis of p-nitrophenyl phosphate hydrolysis at pH 7.2 has been determined. Both IHP and (IHP-Cu) complexes, but not Cu(II) alone, are effective inhibitors of the enzyme and are of the strictly competitive type with Ki values in the microM range. Without added inhibitors present, the kinetic parameters are kcat 5.7 x 10(3) min(-1); and KM, 18 microM. In the presence of 62 microM IHP, kcat was essentially unchanged with an apparent KM of 68 microM giving a Ki of 22 microM. In the presence of an (IHP-Cu) complex (62 microM IHP, 128 microM Cu(II], the apparent KM was 55 microM and Ki was 30 microM. At a ratio of Cu(II):IHP of 6.0 (372:62 microM) the apparent KM was 30 microM and Ki was 94 microM. The inhibitory effect of (IHP-Cu) complexes thus decreases as the IHP binding sites for cupric ions become saturated. A high ionic strength environment markedly reduces the inhibitory effect of IHP. Previous studies have also shown that rates of APase inactivation by (IHP-Cu) complexes are also ionic strength sensitive [1]. The inhibition of APase activity by either IHP or its coordinate complexes with cupric ions is evidence for their interaction at the enzyme's catalytic sites. Such results thus provide support for an essential element of the mechanism previously suggested for the reversible inactivation (as opposed to inhibition) of APase by (IHP-Cu) chelate complexes, viz., that it may be due to a metal ion exchange reaction leading to the formation of a Cu(II)-substituted enzyme. PMID- 1880500 TI - 1H NMR studies on lanthanides substituted transferrins. AB - The binding of lanthanide(III) ions to human serum apotransferrin has been investigated through 1H NMR spectroscopy. Several well resolved isotropically shifted signals have been observed between 100/-100 ppm for the Tm, Tb, Yb and Dy derivatives. Significant spectroscopic inequivalence of the two metal binding sites has been revealed. Differences in the behavior of signals assigned to the C and to the N-terminal site have been observed upon titration with sodium perchlorate. PMID- 1880501 TI - Competition between Li+ and Mg2+ for ATP and ADP in aqueous solution: a multinuclear NMR study. AB - We used 7Li NMR spin-lattice relaxation times and 31P NMR chemical shifts to study the binding of Li+ and Mg2+ to the phosphate moieties of ATP and ADP. To examine the binding of Li+ and Mg2+ to the base and ribose moieties, we used 1H and 13C NMR chemical shifts. The 7Li NMR relaxation times of Li+/Mg2+ mixtures of ATP or ADP increased with increasing concentrations of Mg2+, suggesting competition between the two ions for adenine nucleotides. No significant binding of Li+ and Mg2+ to the base and ribose moieties occurred. At the pH and ionic strength used, 2:1 and 1:1 species of the Li(+)-ATP and Li+-ADP complexes were present, with the 2:1 species predominating. In contrast, 1:1 species predominated for the Mg(2+)-ADP and Mg(2+)-ATP complexes. We calculated the Li(+) nucleotide binding constants in the presence and absence of Mg2+ and found them to be somewhat greater in the presence of Mg2+. Although competition between Li+ and Mg2+ for ATP and ADP phosphate binding sites in solution is consistent with the 31P chemical shift data, the possibility that the Li+ and Mg2+ form mixed complexes with the phosphate groups of ATP or ADP cannot be ruled out. PMID- 1880502 TI - Lead (II)-dithiothreitol equilibria and their potential influence on lead inhibition of 5-aminolevulinic acid dehydratase in in vitro assays. AB - Dithiothreitol (threo-2,3-dihydroxy-1,4-dithiobutane = DTT) has recently been used to activate 5-aminolevulinic acid dehydratase in kinetic studies for the inhibition of this zinc enzyme by lead. Since the DTT molecule contains donor groups capable of forming metal ion complexes, its presence in the experimental medium used for this kind of assay may largely influence the concentration of lead available for the active sites of the enzyme. Before any quantitative investigation of this phenomenon can be contemplated, all possible complexes formed by lead with DTT must first be identified and their stabilities determined. Accordingly, formation equilibria of DTT complexes with lead(II) have been investigated under physiological conditions (37 degrees C, NaCl, 0.15 mol. dm-3 using glass electrode potentiometry. Corresponding stability constants were refined with MINIQUAD and ESTA computer programs. DTT log protonation constants have been found equal to 9.811 +/- 0.002 and 18.672 +/- 0.002. The following lead dithiothreitol complexes have been characterized: ML (12.243 +/- 0.063), MLH-1 (2.391 +/- 0.061), M2LH-1 (13.285 +/- 0.059), and M4L3 (51.668 +/- 0.157). Appropriate computer simulations show that the interactions of the two reactants are indeed most significant under the pH and concentration conditions used in the above mentioned biological investigations. In particular, the influence of lead(II)-DTT equilibria on the free concentration of lead available for the active sites of the enzyme is described. PMID- 1880503 TI - Adducts of nitroimidazole derivatives with rhodium(II) carboxylates: syntheses, characterization, and evaluation of antichagasic activities. AB - Adducts of several rhodium(II) carboxylates with two antiparasitic nitroimidazole ligands were prepared and characterized by elemental microanalysis, thermogravimetry, spectrophotometry (IR, UV, and visible), and proton magnetic resonance. Results of elemental and thermogravimetric analyses were consistent with the general formula Rh2(RCOO)4. 2L (R = aliphatic or aromatic carboxylic groups; L = metronidazole or benznidazole). The reddish-brown color of the adducts as well as their visible spectra suggest axial coordination of the nitroimidazole ligands through nitrogen atoms. NMR spectra indicate N3 as the coordinating atoms. Screening tests performed on cultures of T. cruzi indicate that aliphatic complexes--particularly propionate and acetate adducts--were more active than their aromatic counterparts, the same being observed with benznidazole adducts in relation to their metronidazole analogues. Evaluated for their usefulness as transfusion prophylactic agents against Chagas' disease, propionate derivatives failed to sterilize T. cruzi infected blood. An oral toxicity assay in mice showed mild toxic effects with daily doses of 5 mg/kg for 20 days. PMID- 1880504 TI - Cellular uptake and toxicity study of cis-bis(6-aminoquinoline) dichloroplatinum (II). AB - A fluorescent analog of cis-diamminedichloroplatinum(II), cis-bis(6 aminoquinoline)dichloroplatinum(II), was prepared from K2[PtCl4] and 6 aminoquinoline (AQL). HPLC of the thiourea derivative of the new complex showed that it has the cis-configuration. The Pt-AQL complex and the parent ligand AQL were evaluated for biological activity and cellular uptake, using the ciliate Tetrahymena pigmentosa. The complex was relatively nontoxic at the tested levels below 5 x 10(-4) M, but did exhibit inhibition of culture growth at 5 x 10(-4) M. Measurement of cellular uptake of the Pt-AQL complex demonstrated incorporation into the cell, with localization primarily within the vacuoles of the cells. Comparable measurement of the parent ligand AQL showed little measurable cellular uptake. PMID- 1880505 TI - Shikimic acid complexes of platinum. Preparation, reactivity, and antitumor activity of (R,R-1,2-diaminocyclohexane) bis(shikimato) platinum(II). Evidence for a novel rearrangement involving platinum-carbon bond formation. AB - The complex (R,R-1,2-diaminocyclohexane)bis(shikimato)platinum(II) (shikimato = the anion of 3R,4S,5R-trihydroxy-1-cyclohexene-1-carboxylic acid), I, has been synthesized and purified by high performance liquid chromatography (HPLC). The complex is only moderately stable in aqueous solution. Its major hydrolysis product, also purified by HPLC, is proposed to be a unique complex type in which a single shikimate group is coordinated through both the carboxylate oxygen and the C(2) vinylic carbon of the shikimate moiety [Pt(R,R-dach)(O,C-shikimato)], II. In vitro, complex I is active against L1210 leukemia and against an L1210 cell line with acquired resistance to cisplatin. In vivo, the complex is active against L1210, P388, and B16 melanoma; this activity is highly schedule dependent. Complex II is also active against L1210 leukemia. PMID- 1880507 TI - Rhazes (850-923). PMID- 1880506 TI - Diffuse axonal injury in non-missile head injury. PMID- 1880508 TI - MRI in the management of suspected cervical spondylotic myelopathy. AB - One hundred and two patients with suspected cervical spondylotic myelopathy were prospectively investigated using MRI as the initial imaging technique. The aim was to discover if clinicians could manage patients with MRI alone, or if they would find a second investigation necessary. Eighty two patients were managed using MRI alone, 34 of whom were treated surgically. Twenty patients had a second investigation: a myelogram in 18 and a CT myelogram in two. This was performed in nine patients to exclude structural pathology in the thoracic or lumbar region (which was not examined with MRI), and in 11 to obtain more specific information about the cervical region. Only five of these 20 patients had surgical treatment. The diagnosis changed after the second investigation in four patients, but management was not influenced in any of these. MRI is a satisfactory alternative to myelography for most patients with suspected cervical spondylotic myelopathy. PMID- 1880509 TI - Single photon emission computed tomography in patients with acute hydrocephalus or with cerebral ischaemia after subarachnoid haemorrhage. AB - Using single photon emission computed tomography (SPECT), cerebral blood flow was studied in eight patients with gradual deterioration in the level of consciousness after subarachnoid haemorrhage. Four had cerebral ischaemia and four had acute hydrocephalus. In patients with cerebral ischaemia, single photon emission computed tomography scanning showed multiple regions with decreased uptake of technetium-99M labelled d,l-hexamethyl-propylene amine oxime (99mTcHM PAO) mainly in watershed areas. In patients with acute hydrocephalus, decreased uptake was seen mainly in the basal parts of the brain: around the third ventricle, around the temporal horns of the lateral ventricles, and in the basal part of the frontal lobe. After serial lumbar puncture, there was improvement of the uptake of 99mTc HM-PAO in these basal areas in three (convincingly in two and slightly in the other) of the four patients accompanied by clinical improvement in these three patients. These results suggest that patients with acute hydrocephalus and impaired consciousness after SAH, in contrast to patients with cerebral ischaemia, have decreased cerebral blood flow predominantly in the basal parts of the brain. PMID- 1880510 TI - Neurosarcoidosis--demonstration of meningeal disease by gadolinium enhanced magnetic resonance imaging. AB - Arriving at a firm diagnosis of neurosarcoidosis continues to pose serious problems, particularly when evidence of granulomatous disease outside the nervous system is lacking. The commonest mode of presentation of neurosarcoidosis is with cranial nerve palsies. Two cases of presumed neurosarcoidosis with cranial nerve palsies showed clear evidence of focal meningeal disease on gadolinium-DTPA enhanced MRI brain scans. Although not specific for sarcoidosis, this technique may be very useful in aiding the diagnosis in suspected cases. PMID- 1880511 TI - Wildervanck or cervico-oculo-acoustic syndrome and MRI findings. AB - In 1952, Wildervanck described the first case of what he styled the cervico-oculo acoustic (COA) syndrome. This comprises Klippel Feil's (KF) anomaly (congenitally fused cervical vertebrae), congenital sensorineural deafness and Duane's retraction syndrome (deficient abduction with retraction on adduction). Since that original paper, there have been further reports describing this triad, either completely or incompletely. A further case of this syndrome is reported and the first report of MRI head scan findings in this condition is presented. In addition, the origin of mirror movements observed as part of the KF syndrome are discussed. PMID- 1880512 TI - Central motor pathways in patients with mirror movements. AB - Central motor pathways were investigated in three patients with congenital mirror movements using magnetic motor cortex stimulation. Response thresholds, amplitudes and latencies were normal. The projection of the corticomotoneuronal pathways was assessed by placing the coil over the vertex and comparing the size of responses in the first dorsal interosseous (FDI) muscles evoked by anticlockwise and clockwise [corrected] coil currents. In normal subjects, right FDI responses are larger with anticlockwise currents than with clockwise [corrected] currents at the same stimulation strength and vice versa. In two out of three patients with congenital mirror movements, this sensitivity of response amplitude to coil current direction was reversed. The third patient with congenital mirror movements and a fourth patient with acquired mirror movements had responses which were normally sensitive to current direction. These findings support the hypothesis that some cases of congenital mirror movements may be due to abnormal projection of corticomotoneuronal pathways. PMID- 1880513 TI - Diurnal variation of essential and physiological tremor. AB - Evaluations were made of the diurnal variations of tremor power at rest, after fatigue and after mass loading, and plasma norepinephrine in patients with familial essential tremor and normal subjects. Diurnal tremor power rhythms for both essential and physiological tremor pursued identical temporal profiles. Plasma norepinephrine levels followed a congruent diurnal pattern with later peak values than the peak values of tremor power. Sympathetic nervous system activity is unlikely to be the cause of diurnal tremor power variation. The consistent diurnal rhythm of tremor power may affect dosage schemes of tremorolytic drugs. PMID- 1880514 TI - Partial, non-thrombotic, superior sagittal sinus occlusion due to occipital skull tumours. AB - Two cases are described in which raised intracranial pressure occurred as a result of superior sagittal sinus (SSS) occlusion by an occipital skull tumour. One was a plasmacytoma, the other a metastatic deposit from a Ewing's sarcoma. The difficulties in diagnosis of this syndrome are illustrated together with the importance and success of appropriate treatment. From the literature it appears possible that these two tumours may be particularly likely to occlude the SSS and the reasons for this are discussed. PMID- 1880515 TI - Motor potentials of bulbocavernosus muscle after transcranial and lumbar magnetic stimulation: comparative study with bulbocavernosus reflex and pudendal evoked potentials. AB - Motor potentials of the bulbocavernosus muscle were recorded in 17 healthy subjects after transcranial and lumbar magnetic stimulation. The latencies (SD) were respectively: 22.9 (1.8) and 5.9 (0.4) ms. The central conduction time was 17.0 (2.5) ms. The bulbocavernosus reflex presented an onset at 34.5 (3.3) ms and a negative peak at 43.1 (3.9) ms. The cortical pudendal evoked potential was W shaped: the first peak had a latency of 35.4 (2.8) ms. The concurrent recording of motor potentials, bulbocavernosus reflex, pudendal evoked potentials gives a measure of peripheral and central, afferent and efferent neurological pathways related to pudendal nerve function. PMID- 1880516 TI - Graded assessment and classification of impaired temperature sensibility in patients with diabetic polyneuropathy. AB - Thermal sensibility was quantitatively assessed in the feet of 46 diabetic patients. In subjects with sensibility deficits the perception threshold for warmth or cold, or of heat pain, was either increased or lost. Four stages of impaired thermal sensibility were defined, and a classification of dysfunction is proposed which could be useful in routine clinical examination of patients with diabetic polyneuropathy. The classification of impaired thermal sensibility correlated significantly with the results of a bedside screening examination aimed at describing the severity of the polyneuropathy in terms of its regional extent. PMID- 1880517 TI - Dementia presenting with aphasia: clinical characteristics. AB - Dementia, a disorder of multiple cognitive functions, may atypically present as an aphasia. The clinical characteristics are reported of 13 patients with up to 14 years of progressive language impairment before developing dementia. In reviewing the literature, it was found that these patients were similar to those reported with progressive aphasia. It is concluded that dementia may present with an anomic, dysfluent language disorder due to the focal left sylvian onset of several dementing illnesses. PMID- 1880518 TI - The neuropsychological sequelae of attempted hanging. AB - Only one report on the neuropsychological sequelae of attempted hanging exists in the English language. Two cases of attempted hanging with subsequent isolated memory deficits are reported. Possible mechanisms for induction of this amnesia are discussed. In these two cases it is most likely that circulatory disturbance produced by the ligatures caused ischaemic hippocampal damage, which in turn led to amnesia. PMID- 1880519 TI - Different types of skew deviation. AB - Although all manifest skew deviations appear the same for the clinician, skew deviation can result from different combinations of dysconjugate vertical ocular deviations. Evidence is presented for three different types of skew deviation when it occurs as a feature of an ocular tilt reaction. In type 1 (utricle) there is upward deviation of both eyes with different amplitudes, as described for otolith Tullio phenomenon in humans. In Type 2 (dorsolateral medulla oblongata) hypertropia of one eye occurs while the other eye remains in the primary position, the hypothetical mechanism of skew deviation in Wallenberg's syndrome. In Type 3 (midbrain tegmentum) there is simultaneous hypertropia of one eye and hypotropia of the other eye, as described for electrical stimulation of midbrain tegmentum in monkeys and observed in clinical cases with a paroxysmal ocular tilt reaction. PMID- 1880520 TI - Post-traumatic syringomyelia following uncomplicated spinal fracture. AB - Two cases of post-traumatic syringomyelia presenting 10 and 41 years after spinal injuries that had caused lumbar vertebral fractures but no lasting neurological deficits are reported. In both patients the caudal end of the syrinx cavities, as shown by MRI, corresponded to the level of the previous vertebral fractures. Patients presenting with post-traumatic syringomyelia after uncomplicated spinal fracture are very rare, and the significance of the past history of spinal trauma may be overlooked. PMID- 1880522 TI - Shunt failure caused by valve collapse. AB - Shunt failure due to collapse of the Mini-Holter valve was observed 13 times in 11 out of 179 children with an implanted Mini-Holter ventriculo-peritoneal (VP) or ventriculo-atrial (VA) shunt during a 10 year period. Intussusception of the proximal or distal end of the valve thus caused a shunt failure rate of 6% of the children in this series. Two children experienced this complication twice. All collapsed valves were part of a VP shunt system. Because of this experience use of the mini valve was abandoned and an adult Holter valve was implanted in children over the age of one month. Breakdown of this particular valve has not occurred in 102 children and two hundred adults with the adult Holter shunt system. PMID- 1880521 TI - Allele frequencies of the third component of complement (C3) in MS patients. AB - No difference was found in the allele frequency of C3 (third component of complement) in 129 multiple sclerosis (MS) patients compared with both 69 controls or with similar reported controls from the published literature. An association cannot be confirmed between C3 and MS. PMID- 1880523 TI - Trapezius muscle atrophy after whiplash injury: accessory nerve or cervical plexus lesion? PMID- 1880524 TI - Cysticercus immunoblot assay in Indian patients with single small enhancing CT lesions. PMID- 1880525 TI - Chronic hemidystonia following acute dystonic reaction to thiethylperazine. PMID- 1880526 TI - Bilateral metastases in the cerebellopontine angle. PMID- 1880527 TI - Myasthenia gravis aggravated by pyrantel pamoate. PMID- 1880528 TI - Myxopapillary ependymomas arising from nerve roots of the spinal cord. PMID- 1880529 TI - Spinal extradural venous haemorrhage controlled by a drawing pin: a new technique in neurosurgery. PMID- 1880530 TI - Quantitative changes during the postnatal maturation of the human visual cortex. AB - Postnatal development of the human visual cortex is characterized by an overshooting growth pattern of its volume with a maximum at 8 postnatal months and by loss of a substantial proportion of its neurons. The highest rate of reduction in neuronal numbers is observed in layers II-IVa, with other layers showing a more gradual postnatal decrease. PMID- 1880531 TI - Intractable hiccup induced by brainstem lesion. AB - Four patients with brainstem lesions presented with intractable hiccup and mild to moderate neurological signs. Two of the patients had been initially diagnosed as having a psychogenic cause for their hiccup. Magnetic resonance imaging (MRI) demonstrated brainstem infarction in one case, tuberculoma at the junction of the medulla oblongata and the cervical spinal cord in two, and a vermian tuberculoma compressing the brainstem in one. The brainstem infarct and one of the medullary tuberculoma were not detected on high resolution enhanced computed tomography. The 3 patients with CNS tuberculoma were free of hiccup 1-5 months after antituberculous chemotherapy. It is proposed that hiccup is not an abnormal reflex, but a myoclonus generated by repetitive activity of the "inspiratory solitary nucleus" due to release of higher nervous system inhibitory/-regulatory control. The neuroanatomical network and the mechanisms underlying the formation of intractable hiccup are outlined. The value of MRI in the initial diagnosis and follow-up of patients with intractable hiccup due to brainstem lesions is emphasised. PMID- 1880532 TI - Trophic effect of angiotensin II, vasopressin and other peptides on the cultured ventral spinal cord of rat embryo. AB - We studied trophic effects of angiotensin II, vasopressin, cholecystokinin, and oxytocin on explanted ventral spinal cord cultures from 13- and 14-day-old rat embryos. There was a significant neurite promoting effect of the spinal cord cultures by using angiotensin II, vasopressin, and cholecystokinin. Cholecystokinin had the most potent effect at any concentrations. The minimum effective concentration was 10(-8) M in angiotensin II and vasopressin and 10( 12) M in cholecystokinin, respectively. The effect of angiotensin II and vasopressin was dependent on concentrations. However, the rate and grade of neurite appearance did not correlate with the concentrations of cholecystokinin. Oxytocin had no neurotrophic effect at any concentrations. Our results demonstrated that angiotensin II, vasopressin and cholecystokinin have neurotrophic effects on the ventral spinal cord in cultures, and may be candidates for therapeutic trials of amyotrophic lateral sclerosis. PMID- 1880533 TI - Morphometric analysis of a model of spinal cord injury in guinea pigs, with behavioral evidence of delayed secondary pathology. AB - A model of spinal cord trauma in guinea pigs is described, based on the concept of compression to a set thickness, as an alternative to compression or contusion with a set force or displacement. The model is technically simple and reliable and circumvents some of the biomechanical problems of contusion techniques. It was designed initially to produce moderate injuries, allowing significant recovery of function. A pair of forceps was modified to form an instrument to compress the spinal cord laterally, over a 5-mm length, to a thickness of 1.2 mm. Such compression injuries of the lower thoracic cord were produced in 12 anesthetized, adult guinea pigs, and the outcome monitored, using successive behavioral tests and morphometry of the lesion at 2-3 months. Chronic histopathology was examined quantitatively with line-sampling of axons in 1 micron plastic sections through the lesion center, stained with toluidine blue. The type and distribution of damage to axons was similar to that seen following weight-drop contusion trauma in cats. Spinal cord function was examined by means of hindlimb reflex testing and motor behavior, vestibulospinal reflex testing, and mapping the receptive field of the cutaneus trunci muscle (CTM) reflex. These injuries characteristically resulted in a delayed onset of functional deficits at 1-2 days after injury, followed by partial recovery over the course of several weeks. Overall, functional outcome correlated significantly with the number of surviving axons in the lesion. The phenomenon of "secondary" pathology was striking at the behavioral level, whereas evidence of delayed injury has been indirect in most animal models. The onset of this secondary process occurred with a longer delay than has been assumed or implied by most suggested mechanisms of secondary pathology. The time course of secondary loss and recovery may be related to that of the inflammatory response at the injury site, particularly the phagocytic activity of macrophages. PMID- 1880534 TI - Somatosensory evoked potentials following stimulation of median and tibial nerves in patients with localized intracerebral hemorrhage: correlations with clinical and CT findings. AB - Median and tibial somatosensory evoked potentials (SEPs) were performed on 38 patients with localized intracerebral hemorrhage, 23 with thalamic hemorrhage and 15 with putaminal hemorrhage. Of 65 arms and 62 legs examined, cerebral evoked responses of 60 arms and 50 legs were diagnosed as abnormal. The abnormal findings in scalp-recorded SEPs consisted of a reduction in amplitude, loss of waves and delay in peak latencies. The SEP abnormalities were not indicative of location of hemorrhage. Absence of SEPs was more frequently observed in large hemorrhages and at the early stage. Substantial improvement in SEPs was observed over several months after stroke in many limbs. Motor function as evaluated with Brunnstrom staging of the upper limbs whose SEPs were absent was lower than that whose SEPs were evoked, but that was not observed in the lower limbs because in some cases absence of SEPs coexisted with good motor function. Loss of SEP waves had a significant correlation with disturbed deep sensation. The median and tibial SEPs provided an excellent clinical correlation with the patients' improvement over several months. PMID- 1880535 TI - Tapia's syndrome caused by Paracoccidioidis brasiliensis. AB - Tapia's syndrome is due to extracranial involvement of the XIIth nerve and the recurrent laryngeal branch of the Xth nerve. There is ipsilateral paralysis of vocal cords, soft palate and tongue. The main causes are parotid and other tumors or injuries to the high neck. We describe here a Brazilian female patient who presented with a lesion in the nasal mucosa, and soon after had dysphagia and dysphonia. Examination revealed paralysis of the soft palate, vocal cords and tongue ipsilaterally. Microscopic examination of the lesion in the nasal mucosa revealed the presence of the fungus. The patient was treated with sulfonamide and ketoconasol. PMID- 1880536 TI - The role of complement in myelin phagocytosis during PNS wallerian degeneration. AB - Myelin removal in nerves undergoing wallerian degeneration mainly depends on invading, non-resident macrophages. The present study clarifies the role of serum complement components in this process in vitro and in vivo. Macrophages cocultured with degenerating nerves in vitro were unable to invade these nerves in the presence of C3-deficient serum. Application of C3-deficient serum subsequent to cellular invasion abolished the myelin phagocytic capacity of the invaded macrophages. This indicates that opsonization of myelin by complement components is necessary in myelin ingestion via macrophage receptors. In vivo, a monoclonal antibody to the macrophage complement receptor type 3 (CR3) significantly reduced myelin phagocytosis. Immunohistochemistry with anti-C3 antibodies showed a marked reaction in degenerating nerves. Immunoelectron microscopy localized C3 particles at the degenerating myelin sheaths. Haematogenous cells, invading the degenerating nerves, also showed a strong reaction for C3 in their cytoplasm. These results indicate that complement components play a critical role both in macrophage invasion of degenerating nerves and in the ingestion of myelin by these cells. PMID- 1880537 TI - Physiological significance of fatty acid elongation system in adrenoleukodystrophy. AB - We studied the metabolism of radioactive fatty acids in cultured skin fibroblasts from patients with adrenoleukodystrophy (ALD) and Zellweger syndrome (ZS) to clarify the physiological significance of the fatty acid elongation system in the accumulation of very long chain fatty acids (VLFA) in ALD. A substantial amount of radioactive C26:0 was synthesized from [18-14C]stearic acid by ALD and ZS fibroblasts, whereas radioactive C26:0 was not detected in control fibroblasts. Kinetic studies demonstrated that the production of radioactive C24:0 and C26:0 in ALD fibroblasts is higher than that of ZS fibroblasts, which suggests that the fatty acid elongation activity plays an important role for the accumulation of VLFA in ALD, in addition to the decreased VLFA oxidation activities. The addition of monounsaturated fatty acids including oleic acid and erucic acid specifically lowered the formation rate of VLFA without any significant effect on degradation activities of VLFA both in ALD and control fibroblasts. The results suggest that the mechanism of decrease of VLFA by administration of monounsaturated fatty acids is based on the inhibition of fatty acid elongation activity. PMID- 1880538 TI - Hereditary spastic dystonia: a new mitochondrial encephalopathy? Putaminal necrosis as a diagnostic sign. AB - A large kindred, in which either Leber's hereditary optic atrophy, or a hereditary spastic dystonia, or a combination of both manifested over many generations was restudied after the first report on it in 1964. NMR scans revealed bilateral, and, in two patients with hemidystonia, unilateral necrosis with shrinkage of the putamen, in one case associated with total disappearance of the head of the caudate nucleus. Except for age-appropriate cortical atrophy in one instance, no other changes were observed in the brain, brainstem, and cerebellum. The putaminal necrosis appears as typical "striatal slits" on the NMR scans. It is argued that this rare disease, since the princeps description in 1964 only reported in England (1986) and the U.S.A (1986), is most likely a singular type of mitochondrial encephalopathy: it is associated with Leber's optic atrophy, and the NMR changes observed have been signalled in other mitochondrial encephalomyelopathies, such as Leigh's disease and MELAS. PMID- 1880539 TI - Presence of serum anti-human T-lymphotropic virus type I (HTLV-I) IgM antibodies means persistent active replication of HTLV-I in HTLV-I-associated myelopathy. AB - We investigated serum IgM antibodies against human T-lymphotropic virus type I (HTLV-I) in 29 HTLV-I associated myelopathy (HAM) patients and 34 HTLV-I carriers, using western blot analysis. Anti-HTLV-I IgM was detected in all 6 post transfusional HAM patients and in 19 of 23 (83%) HAM patients with no history of blood transfusion, but in only 4 of 21 (19%) HTLV-I carriers. In HAM patients, HTLV-I proviral DNA integrated into peripheral blood lymphocyte (PBL) was detected by Southern blot analysis in all of the 6 (100%) and 18 of the 23 (78%). In contrast, it was detected in only 2 of 25 (8%) HTLV-I carriers. For the serum anti-HTLV-I IgM and HTLV-I provirus in PBL, the differences between the HAM and HTLV-I carriers were statistically significant (P less than 0.01). Our data indicate that the increased HTLV-I proviral DNA in PBL is produced by the persistent active replication of HTLV-I in HAM. Furthermore, Southern blot analysis showed intense bands in HAM patients with histories of blood transfusion, in whom the progression of the disease had been rapid. We conclude that the persistent active replication of HTLV-I is an important factor in the pathogenesis of HAM. PMID- 1880540 TI - Affinity immunoblotting: rapid and sensitive detection of oligoclonal IgG, IgA and IgM in unconcentrated CSF by agarose isoelectric focusing. AB - Two methods for the investigation of oligoclonal immunoglobulin bands in cerebrospinal fluid are compared. Isoelectric focusing (IEF) in agarose gels combined with a highly sensitive affinity immunoblotting proved to be superior to PAGE-IEF and silver staining regarding detection sensitivity and expenditure of labour. The procedure presented here allows examination of oligoclonal bands not only of IgG, but also of IgA and IgM antibodies in less than 4 h. Oligoclonal IgM bands could be detected in 6 patients with neuroborreliosis or neurosyphilis as well as in one patient with a peripheral neuropathy where other electrophoretic methods, including immunoelectrophoresis, were negative. Oligoclonal IgA bands were demonstrated only in 2 patients with a bacterial infection of the CNS. In patients with multiple sclerosis amounts of IgM and IgA in the CSF were too low to allow investigation of oligoclonal IgM or IgA bands. PMID- 1880541 TI - Total ion content of skeletal and cardiac muscle in the mdx mouse dystrophy: Ca2+ is elevated at all ages. AB - The mdx mouse has been shown to have a gene defect at the locus which is homologous to that which is defective in Duchenne muscular dystrophy and they both lack dystrophin, the protein product of this defective gene. The exact cause of myofibre necrosis in DMD is not known but there is evidence to support a causal relationship between elevated calcium and tissue necrosis. Since the mdx mouse exhibits age-dependent changes in the proportion of tissue necrosis, we have measured total ion content (Ca2+, Na+, K+, and Mg2+) in the heart and skeletal muscle of animals at different ages to determine if ionic changes correlate with reported periods of necrosis. Total calcium is elevated throughout the ages studied (10 days, 30 days and 254-347 days) in both tissues and does not correlate with necrosis, although it appears that pre-necrotic tissues do not exhibit such a wide variation in calcium content as is observed in tissues from older animals. These changes are discussed with reference to the other ions measured and to the regulation of intracellular calcium. PMID- 1880542 TI - Total biopterin levels in the ventricular CSF of patients with Parkinson's disease: a comparison between akineto-rigid and tremor types. AB - Total L-erythro-biopterin (T-BP) levels in the ventricular cerebrospinal fluid (CSF) were measured in 43 patients with Parkinson's disease (PD) and 12 age matched neurological controls. In 5 of the PD patients and 1 control, lumbar CSF T-BP values were also measured. The mean ventricular CSF T-BP level in the PD patients, 15.6 +/- 0.5 pmol/ml (mean +/- SE), was significantly lower than that in the controls (21.3 +/- 1.4 pmol/ml, P less than 0.0001). The mean T-BP concentration in the ventricular CSF was 1.9 times higher than that in the lumbar CSF (P less than 0.0005), indicating a rostrocaudal gradient for the T-BP value in the CSF. When the PD patients were classified according to their predominant clinical features into 24 akineto-rigid (A-R) type and 19 tremor (T) type, there was a significant negative correlation between the T-BP levels and duration of illness only for the A-R type patients (rho = -0.605, P less than 0.005). No such significant correlation was found in the T type patients. These results may indicate a difference of pathophysiological changes in the brain between the 2 types of PD. PMID- 1880544 TI - Temporal patterns of muscle activation for arm movements in three-dimensional space. AB - Little is known about the patterns of muscle activation that subserve arm movement in three-dimensional space. In this study, activation patterns of seven arm muscles were related to the spatial direction of human arm movement. Twenty movement directions defined two orthogonal vertical planes in space. The arm movements were moderately paced; each movement lasted approximately 500 msec. New techniques of EMG analysis were developed to describe the temporal pattern of muscle activation. For each muscle, a principal component analysis revealed a common phasic and tonic waveform for all directions of movement, within one plane. A temporal shifting procedure based on best covariance values revealed activation delays associated with different movement directions. The results show a consistent pattern of temporal shifting of the common waveform for movements in different directions. Coupled with past results showing that activation amplitude is a function of the cosine angle of movement or force direction, the present results suggest a relatively simple control strategy for mechanically complex arm movements: neural circuits produce a common phasic and tonic activation waveform that is scaled in amplitude and delayed in time, depending on the desired movement direction. PMID- 1880543 TI - Does low intracellular pH stop the motion of the Bulla circadian pacemaker? AB - The eye of the mollusk Bulla has proven itself useful as an in vitro neural circadian pacemaker. Here, we report that treatments applied to lower intracellular pH may stop the motion of this circadian pacemaker in a phase dependent manner. Lowering the extracellular pH of the artificial seawater bath to 6.9, or application of the stilbene derivatives 4-acetamido-4' isothiocyanostilbene-2,2'-disulfonic acid (SITS) or 4,4-di-isothiocyanostilbene 2,2'-disulfonic acid (DIDS), abolishes the circadian rhythm in optic nerve compound action-potential frequency. Because these treatments are known to lower intracellular pH, these data suggest that the pacemaker may be inhibited by low intracellular pH. In order to assess the state of the pacemaker during low extracellular pH treatment, pulses of seawater at pH 6.8 were applied, and the phase of the rhythm subsequent to the pulse was observed. All pulses started 1 hr after subjective dusk [circadian time (CT) 13] and were applied to eyes in constant darkness; pulse lengths varied from 4 to 47 hr for different preparations. The phases of the eye rhythms following pulses that ended before subjective dawn (about CT 24) were not different from untreated preparations. However, for pulses longer than 11 hr and therefore ending after subjective dawn, the subsequent phase of the rhythm was a function of the ending time of the pulse. These data suggest that the pacemaker's motion was stopped at dawn during the low-pH treatment and resumed following restoration of normal pH. To distinguish between phase and duration dependence of this effect in the above experiment, phase shifts were obtained to 14-hr pulses of pH 6.8 seawater applied at three different phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880545 TI - Extracellular dopamine and neurotensin in rat prefrontal cortex in vivo: effects of median forebrain bundle stimulation frequency, stimulation pattern, and dopamine autoreceptors. AB - In vivo microdialysis coupled with HPLC and radioimmuno-assay techniques were used to analyze dopamine (DA) and neurotensin (NT) in prefrontal cortical extracellular fluid following electrical stimulation of mesocortical axons. The release (overflow into the extracellular fluid) of both DA and NT increased with increasing number of impulses and with frequency. At the lowest frequency tested (2.5 Hz), DA release was significantly increased, while there was no significant increase in the release of NT. As the frequency of stimulation was increased from 2.5 to 20 Hz, the ratio of extracellular DA:NT decreased exponentially. Stimulation in a burst pattern produced greater release of both DA and NT than tonic stimulation when the number of impulses per second and the total number of impulses were held constant. Furthermore, blockade of DA autoreceptors with sulpiride stereoselectively increased the release of DA while decreasing the release of NT. These data suggest that the release of coexistent molecules (DA and NT) from mesocortical neurons can be influenced by physiological and pharmacological factors such that under certain conditions simultaneous or differential release may occur. PMID- 1880546 TI - Regulatory properties of brain glutamate decarboxylase (GAD): the apoenzyme of GAD is present principally as the smaller of two molecular forms of GAD in brain. AB - The apoenzyme of glutamate decarboxylase [enzyme without bound cofactor, pyridoxal 5'-phosphate (pyridoxal-P)] serves as a reservoir of inactive glutamate decarboxylase (GAD) that can be activated when additional GABA synthesis is required. We have investigated which of two molecular forms of GAD is present as apoenzyme in synaptosomes and in cortex, caudate nucleus, hippocampus, and cerebellum of rat brain. Endogenous glutamate apodecarboxylase (apoGAD) was labeled by incubating extracts of synaptosomes or punches of each region with 32P pyridoxal-P, followed by reduction with NaBH4, to link covalently the 32P pyridoxal-P to GAD. Proteins were separated by SDS-PAGE. Punches from all four brain regions and forebrain synaptosomes contained two forms of GAD with apparent Mrs of 63 and 65 kDa as identified by immunoblotting with four antiGAD sera. Punches and synaptosomes contained a major 32P-pyridoxal-P-labeled band with an apparent Mr of 63 kDa that was stained on immunoblots by the antiGAD serum 1440 and the monoclonal antibody GAD-6, and a minor labeled band at 65 kDa that was stained by the 1440, 6799, and K2 antisera. Synaptosomes contained remarkably few other strongly labeled proteins, but punches contained several other labeled bands. Three additional lines of evidence indicate that the labeled 63-kDa protein is apoGAD: (1) it was purified by immunoaffinity chromatography with the GAD-1 monoclonal antibody; (2) it yielded one major labeled peptide when digested with chymotrypsin, and that peptide appeared identical in peptide-mapping experiments to the labeled active-site peptide isolated from chromatographically prepared rat brain GAD; and (3) its labeling was selectively blocked by 4 deoxypyridoxine 5'-phosphate, a competitive inhibitor of the binding of pyridoxal P to GAD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880547 TI - Protein kinase C alteration is an early biochemical marker in Alzheimer's disease. AB - Neuritic (senile) plaques are a hallmark of the pathology found in the brain of patients afflicted with Alzheimer's disease (AD). Neuritic plaques have been considered to be composed of an amyloid core surrounded by dilated neurites, although the use of anti-beta/A4-protein antibody revealed the presence of diffuse plaques without a nuclear-like central mass or surrounding paired helical filament (PHF)-containing neuritic components. The presence of diffuse plaques without PHF-containing neuritic components strongly suggests that the formation of amyloid precedes the degeneration of neurites that surround amyloid. Diffuse plaques are thus considered to be an early marker of AD pathology. In this article, we report that diffuse plaques, possible markers of early AD pathology, are immunostained with anti-protein kinase C(beta II) [anti-PKC(beta II)] antibodies. The PKC(beta II)-immunoreacting components of the diffuse plaques extend from neurons embedded in the plaques. Immunoelectron microscopy of diffuse and mature neuritic plaques shows that PKC(beta II)-like immunoreactivity in the plaques is closely associated with membranous structures of fine neuronal processes apposed to the amyloid fibers. These fine neuronal processes are distinct from classical neurites found typically in mature neuritic plaques. Furthermore, biochemical analysis demonstrates that PKC abnormalities, but not other AD markers (ubiquitin and A68), were found in the neocortex of clinically nondemented individuals with cortical plaques. Therefore, the PKC alteration in neurons might be involved in the early pathophysiology of AD. PMID- 1880548 TI - The response of area MT and V1 neurons to transparent motion. AB - An important use of motion information is to segment a complex visual scene into surfaces and objects. Transparent motions present a particularly difficult problem for segmentation because more than one velocity vector occurs at each local region in the image, and current machine vision systems fail in these circumstances. The fact that motion transparency is prevalent in natural scenes, and yet artificial systems display an inability to analyze it, suggests that the primate visual system has developed specialized methods for perceiving transparent motion. Also, the currently prevalent model of physiological mechanisms for motion-direction selectivity employs inhibitory interactions between neurons; such interactions would silence neurons under transparent conditions and render the visual system blind to transparent motion. To examine how the primate visual system solves this transparency problem, we recorded the activity of direction-selective cells in the first (area V1) and in a later (area MT) stage in the cortical motion-processing pathway in behaving monkeys. The visual stimuli consisted of random dot patterns forming single moving surfaces, transparent surfaces, and motion discontinuities. We found that area V1 cells responded to their preferred direction of movement even under transparent conditions, whereas area MT cells were suppressed under the transparent condition. These data suggest a simple solution to the transparency problem at the level of area V1. More than one motion vector can be represented at a single retinal location by different subpopulations of neurons tuned to different directions of motion; these subpopulations may represent the early stage for segmenting different, transparent surfaces. The results also suggest that facilitatory mechanisms, which unlike inhibitory interactions are largely unaffected by transparent conditions, play an important role in direction selectivity in area V1. The inhibitory interactions for different motion directions for area MT neurons may contribute to a mechanism for smoothing or averaging the velocity field, computations thought to be necessary for reducing noise and interpolating moving surfaces from sparse information. PMID- 1880549 TI - Mossy fiber synaptic reorganization induced by kindling: time course of development, progression, and permanence. AB - Recent studies have revealed that mossy fiber axons of granule cells in the dentate gyrus undergo reorganization of their terminal projections in both animal models of epilepsy and human epilepsy. This synaptic reorganization has been demonstrated by the Timm method, a histochemical technique that selectively labels synaptic terminals of mossy fibers because of their high zinc content. It has been generally presumed that the reorganization of the terminal projections of the mossy fiber pathway is a consequence of axonal sprouting and synaptogenesis by mossy fibers. To evaluate this possibility further, the time course for development of Timm granules, which correspond ultrastructurally to mossy fiber synaptic terminals, was examined in the supragranular layer of the dentate gyrus at the initiation of kindling stimulation with an improved scoring method for assessment of alterations in Timm histochemistry. The progression and permanence of this histological alteration were similarly evaluated during the behavioral and electrographic evolution of kindling evoked by perforant path, amygdala, or olfactory bulb stimulation. Mossy fiber synaptic terminals developed in the supragranular region of the dentate gyrus by 4 d after initiation of kindling stimulation in a time course compatible with axon sprouting. The induced alterations in the terminal projections of the mossy fiber pathway progressed with the evolution of behavioral kindled seizures, became permanent in parallel with the development of longlasting susceptibility to evoked seizures, and were observed as long as 8 months after the last evoked kindled seizure. The results demonstrated a strong correlation between mossy fiber synaptic reorganization and the development, progression, and permanence of the kindling phenomenon. PMID- 1880550 TI - The postsynaptic inhibitory control of lumbar motoneurons during the atonia of active sleep: effect of strychnine on motoneuron properties. AB - The present study examined the effects of strychnine on the tonic hyperpolarization and the changes in membrane properties of lumbar motoneurons that occur during active sleep. To carry out these studies, intracellular recordings from lumbar motoneurons were combined with the juxtacellular microiontophoretic application of strychnine in chronic, undrugged, normally respiring cats. During active sleep, compared to quiet sleep, motoneurons that were not exposed to strychnine exhibited tonic hyperpolarization, a decrease in cell excitability, and an increase in membrane conductance; they were also bombarded by high-frequency, large-amplitude IPSPs. In conjunction with the juxtacellular application of strychnine, there was a marked reduction in the degree of hyperpolarization during active sleep; motoneuron excitability was no longer suppressed, and there was a reduction in the increase in membrane conductance. In addition, the large-amplitude IPSPs were blocked. These results identify glycine as the neurotransmitter responsible for the state-dependent changes in membrane properties and the hyperpolarization of motoneurons that takes place during active sleep. PMID- 1880551 TI - Compensatory elevation of acetylcholine synthesis in vivo by cholinergic neurons surviving partial lesions of the septohippocampal pathway. AB - The present study characterized the effects of partial destruction of the cholinergic septohippocampal pathway on transmitter functions of surviving cholinergic neurons in the hippocampus. Partial and full fimbrial transections were performed, and 3 weeks after lesioning, cholinergic functions were assessed in vivo and in vitro. Hippocampal ChAT activity and the capacity of hippocampal slices to synthesize [3H]ACh in vitro decreased by 35% and 45%, respectively, following partial fimbrial lesions and by 68% and 85%, respectively, following full fimbrial lesions. [3H]ACh release from hippocampal slices in vitro was decreased by 57% and 87%, respectively, following partial and full fimbrial lesions. Partial lesions decreased high-affinity choline uptake into hippocampal synaptosomes by 52%. In contrast to the significant reductions in cholinergic parameters measured in vitro after partial fimbrial lesions, such partial lesions did not significantly alter in vivo measures of hippocampal cholinergic function. Levels of endogenous ACh and choline measured in the hippocampus following partial lesions were similar to that of control values. Also, the hippocampal content of newly synthesized [2H4]ACh and the [2H4]ACh synthesis rate were not significantly different from control values. However, following full fimbrial lesions, in vivo measures of hippocampal cholinergic function were decreased to a degree similar to that observed in vitro. Hippocampal levels of endogenous ACh and [2H4]ACh and the synthesis rate for [2H4]ACh were decreased by 73%, 72%, and 83%, respectively. These results suggest that, following partial destruction of afferent cholinergic fibers that innervate the hippocampal formation, residual cholinergic neurons are able to upregulate their capacity to synthesize and store ACh in vivo, thus compensating for lesion-induced losses of cholinergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880552 TI - Regulation of putative muscle-derived neurotrophic factors by muscle activity and innervation: in vivo and in vitro studies. AB - The normal embryonic development of spinal cord motoneurons (MNs) involves the proliferation of precursor cells followed by the degeneration of approximately 50% of postmitotic MNs during the period when nerve-muscle connections are being established. The death of MNs in vivo can be ameliorated by activity blockade and by treatment with muscle extracts. Muscle activity and innervation have been suggested to regulate the availability of putative muscle-derived neurotrophic agent(s), and MNs are thought to compete for limited amounts of these trophic agents during normal development. Thus, activity and innervation are thought to regulate MN survival by modulating trophic factor availability. We have tested this notion by examining MN survival in vivo and ChAT development in spinal cord neurons in vitro following treatments with partially purified muscle extracts from normally active, paralyzed (genetically or pharmacologically), aneural, denervated, slow tonic, and fast-twitch muscles from embryonic and postnatal animals. Extracts from active and chronically inactive embryonic avian and mouse muscles were found to be equally effective in promoting the in vivo survival of MNs in the chick embryo. Similarly, extracts from fast-twitch and slow tonic postnatal avian muscles did not differ in their ability to promote both MN survival in vivo and ChAT activity in vitro. Although aneural and control embryonic muscle extract had similar effects on ChAT development in vitro, aneural muscle extract contained somewhat less MN survival-promoting activity when tested in vivo. By contrast, denervated postnatal muscle extract was more effective in promoting both MN survival in vivo and ChAT activity in vitro than age-matched control muscle extract.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880553 TI - Outward currents in isolated ventral cochlear nucleus neurons. AB - Neurons of the ventral cochlear nucleus (VCN) perform diverse information processing tasks on incoming activity from the auditory nerve. We have investigated the cellular basis for functional diversity in VCN cells by characterizing the outward membrane conductances of acutely isolated cells using whole-cell, tight-seal, current- and voltage-clamp techniques. The electrical responses of isolated cells fall into two broad categories. Type 1 cells respond to small depolarizations with a regular train of action potentials. Under voltage clamp, these cells exhibit a noninactivating outward current for voltage steps positive to -35 mV. Analysis of tail currents reveals two exponentially decaying components with slightly different voltage dependence. These currents reverse at 73 mV, near the potassium equilibrium potential of -84 mV, and are blocked by tetraethylammonium (TEA). The major outward current in Type I cells thus appears to be mediated by potassium channels. In contrast to Type I cells, Type II cells respond to small depolarizations with only one to three short-latency action potentials and exhibit strong rectification around -70 mV. Under voltage clamp, these cells exhibit a noninactivating outward current with a threshold near -70 mV. Analysis of tail currents reveals two components with different voltage sensitivity and kinetics. A low-threshold current with slow kinetics is partly activated at rest. This current reverses at -77 mV and is blocked by 4 aminopyridine (4-AP) but is only partly affected by TEA. The other component is a high-threshold current activated by steps positive to -35 mV. This current is blocked by TEA, but not by 4-AP. A simple model based on the voltage dependence and kinetics of the slow low-threshold outward current in Type II cells was developed. The model produces current- and voltage-clamp responses that resemble those recorded experimentally. Our results indicate that the two major classes of acoustic response properties of VCN neurons are in part attributable to the types of outward (potassium) conductances present in these cells. The low-threshold conductance in the Type II (bushy) cells probably plays a role in the preservation of information about the acoustic stimulus phase from the auditory nerve to central auditory nuclei involved in low-frequency sound localization. PMID- 1880554 TI - Evidence that protein constituents of postsynaptic membrane specializations are locally synthesized: analysis of proteins synthesized within synaptosomes. AB - Previous studies have led to the hypothesis that some proteins of the postsynaptic membrane are locally synthesized at postsynaptic sites. To evaluate this hypothesis, synaptosome fractions that included fragments of dendrites were allowed to incorporate labeled amino acid into protein. The labeled synaptosomes were then subfractionated to the level of the synaptic plasma membrane (SPM) and then the synaptic junctional complex (SJC). The specific activity (cpm/microgram protein) of the synaptosome fraction and its subfractions was assessed by scintillation counting and protein assay, and labeled polypeptides were characterized by SDS-PAGE and fluorography. The contribution of mitochondrial and eucaryotic protein synthesis to the overall incorporation was evaluated using cycloheximide (CYC), a eucaryotic protein synthesis inhibitor, and chloramphenicol (CAP), a mitochondrial protein synthesis inhibitor. Both the SPM and the SJC subfractions obtained from labeled synaptosomes contained labeled polypeptides. The SPM from labeled synaptosomes had a specific activity approximately equal to that of other nonmitochondrial membrane components of the synaptosome. Thus, labeling of the SPM was not due to contamination by these other labeled membrane components. The mitochondrial fraction had the highest specific activity of the membrane components of the labeled synaptosome, but the specific activity was reduced by 47% in mitochondrial fractions from CAP-treated synaptosomes, while the specific activity of the SPM was not reduced by this treatment. Thus, SPM labeling is not due to mitochondrial contamination. The specific activity of the detergent-insoluble SJC was comparable to that of the SPM from which it was derived. The possibility of labeling of SPM and SJC by contamination with soluble proteins was assessed by adding labeled soluble proteins to a cold synaptosome preparation that was then subfractionated to obtain the SPM and SJC. There was no detectable binding of labeled soluble proteins to the SPM or SJC. These results support the hypothesis that some synaptic proteins are locally synthesized. Fluorographs of SDS gels of SPM from labeled synaptosomes revealed labeled bands at approximate molecular weights of 14, 18, 26, 28, 36, 38, 42, 45, 55, 60, and 116 kDa. Six of these labeled polypeptides at 38, 42, 45, 55, 60, and 116 kDa were still evident in fluorographs of the synaptic junctional complex from labeled synaptosomes. None of these labeled bands were seen in fluorographs of SPM and SJC from CYC-treated synaptosomes, whereas they were still present in fluorographs of CAP-treated synaptosomes. These labeled polypeptides are therefore produced by eucaryotic ribosomal systems.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1880555 TI - A comparative study of the behavioral deficits following lesions of various parts of the zebra finch song system: implications for vocal learning. AB - Song production in song birds is controlled by an efferent pathway. Appended to this pathway is a "recursive loop" that is necessary for song acquisition but not for the production of learned song. Since zebra finches learn their song by imitating external models, we speculated that the importance of the recursive loop for learning might derive from its processing of auditory feedback during song acquisition. This hypothesis was tested by comparing the effects on song in birds deafened early in life and birds with early lesions in either of two nuclei -Area X and the lateral magnocellular nucleus of the anterior neostriatum (LMAN). These nuclei are part of the recursive loop. The three treatments affected song development differently, as reflected by various parameters of the adult song of these birds. Whereas LMAN lesions resulted in songs with monotonous repetitions of a single note complex, songs of Area X-lesioned birds consisted of rambling series of unusually long and variable notes. Furthermore, whereas song of LMAN lesioned birds stabilized early, song stability as seen in intact birds was never achieved in Area X-lesioned birds. Early deafness also resulted in poorly structured and unstable song. We conclude that Area X and LMAN contribute differently to song acquisition: the song variability that is typical of vocal development persists following early deafness or lesions of Area X but ends abruptly following removal of LMAN. Apparently, LMAN plays a crucial role in fostering the kinds of circuit plasticity necessary for learning. PMID- 1880556 TI - Amelioration of delayed neuronal death in the hippocampus by nerve growth factor. AB - Selective neuronal death in the CA1 sector of the hippocampus [delayed neuronal death (DND)] develops several days after transient global cerebral ischemia in rodents. Because NGF plays a potential role in neuronal survival, it was decided to study its effect in DND. We report here that intraventricular injection of NGF either before or after 5 min forebrain ischemia in the Mongolian gerbil significantly reduced the occurrence of DND. The tissue content of NGF in the hippocampus was decreased 2 d after ischemia and recovered to the preischemic level by 1 week. By the Golgi staining technique, changes first began in the dendrites of affected neurons as early as 3 hr. Such changes could be ameliorated by NGF treatment. Although previous knowledge of NGF is limited to the survival of cholinergic neurons in the CNS, it is assumed that other mechanisms must be operating in the hippocampus, for example, postsynaptic modification at dendrites or aberrant expression of NGF receptors possibly at the initial excitation period by glutamate. Furthermore, because previous work has shown that inhibition of protein synthesis reduces the occurrence of DND, a program leading to cell death might also be operating via de novo synthesis of certain protein(s), collectively termed "killer protein," because of a lack of NGF. PMID- 1880557 TI - Contribution of discography to the diagnosis and treatment of lumbar disc herniation. AB - In this study, based on 600 cases of lumbar disc herniation treated by chemonucleolysis, the authors underline the importance of performing good discography and interpreting its results. A discographic classification of intervertebral disc deterioration is suggested. A CT-discographic study is reported and its results are compared with those of standard discography. On the basis of these studies, the authors have established methodological data concerning the efficacy of chemonucleolysis and its evaluation. PMID- 1880558 TI - Cervical cord compression in scleroderma. One case. AB - The cervical spine is rarely involved in scleroderma. The lesions reported here consisted of osteolysis of the posterior arches disturbing vertebral statics, and exuberant calcifications responsible for spinal cord compression by stenosis of the vertebral canal. PMID- 1880559 TI - The perispinal spaces. Constitution, organization and relations with the cerebrospinal fluid (CSF). AB - In this study the structures of the three meningeal membranes which surround the spinal cord and delineate the perispinal spaces are described. The pia mater is composed of a deep layer and a superficial layer. This structural arrangement accounts for the relations of the pia mater with the spinal vessels and the cerebrospinal fluid (CSF). The morphology, structure and landmark value of the denticulate ligament are then defined. Following a brief description of the dura mater and the arachnoidea, the arrangement of the meningeal sleeves of the spinal nerves is detailed. Meningeal structures similar to the cranial arachnoidal granulations are described, and the question of CSF physiology is considered. The secretion and circulation of the CSF are briefly described, and the problem of spinal resorption is discussed. CSF resorption can be effected by ascending, lymphatic or venous routes. PMID- 1880560 TI - Intracerebral stenosing arteriopathies. Contribution of three radiological techniques to the diagnosis. AB - Fifty-one patients with intracerebral stenosing arteriopathy were studied by computerized tomography (CT), magnetic resonance imaging (MRI) and cerebral arteriography. Clinical symptoms were varied, included impaired cognitive functions, progressive neurological deficit, headache and vomiting, and were sometimes not suggestives of the diagnosis. CT scans of the brain were normal in 25 percent of the cases or they were not probative because of various and non specific abnormalities (hypodensity of various types or haemorrhagic hyperdensity). MRI always showed abnormalities but in many cases the lesions observed on T2-weighted images consisted of non-specific focal areas of high intensity signal in the white matter. High-intensity signals in both white matter and cortex seemed to be more suggestive of the diagnosis. In this as in other studies, arteriography therefore remains the reference examination for stenosing arteriopathies. Inflammatory, infectious and atheromatous processes are the main causes of these arterial lesions. The aetiological value of radiological examinations is poor, and in most cases the morphology and distribution of the lesions does not point to any specific origin. However, herpes zoster arteritis usually affects the proximal segments of the anterior and middle cerebral arteries and spares the carotid siphon. PMID- 1880561 TI - Anterior and posterior hypopituitarism with pituitary stalk abnormalities. AB - Hypopituitarism and diabetes insipidus are often idiopathic conditions. A retrospective study of 6 cases of diabetes insipidus and 8 cases of partial or global idiopathic anterior hypopituitarism has shown that MRI is of considerable value to detect abnormalities of the pituitary stalk or hypothalamo-pituitary "relay". On the basis of MRI findings, some cases of idiopathic hypopituitarism can now be grouped together in a new entity which may be called hypopituitarism due to neonatal transection of the pituitary stalk. PMID- 1880562 TI - Hydrolysed microspheres from cross-linked polymethyl methacrylate (Hydrogel). A new embolic material for interventional neuroradiology. AB - Highly hydrophilic, perfectly smooth and spherical microspheres have been synthetized. These non-biodegradable microspheres absorb water in varying degrees and can be injected easily through microcatheters due to their slippery and compressible characteristics. The material was successfully used for embolization of 4 vascular intracranial tumours and 2 spinal vascular lesions in the cervical region, by superselective delivery. Histopathology confirmed absolute inertness of the microspheres. PMID- 1880563 TI - Antenatal diagnosis of pelvic hydronephrosis: assessment of renal function and drainage as a guide to management. AB - The optimal management of children with antenatally diagnosed unilateral hydronephrotic kidneys is unclear. We have monitored renal function and drainage using 99mTc-DTPA renography in 77 children with such kidneys presenting at 1-14 mo of age with the aims of throwing light on the natural history of the condition and evaluating the response of the kidney to pyeloplasty. Since management was independent of the drainage criteria on renography, the opportunity also was presented to evaluate the efficacy of diuretic renography for diagnosing obstruction in these children. Follow-up ranged between 1 and 6 yr, during which renography was performed between 2 and 6 times in each patient. Thirty-nine patients were treated conservatively, while 30 patients underwent pyeloplasty at varying times after presentation. No overall significant change in function was observed either in the nonoperated children or as a result of surgery. This also applied to sub-groups of children with poor drainage. Function improved significantly, however, in a sub-group of nonoperated children who presented with impaired function in the hydronephrotic kidney. Surgery, although having no overall effect on function, significantly improved drainage. As a means of identifying obstruction, 99mTc-DTPA diuretic renography was unreliable, erroneously indicating obstruction in 24 nonoperated children in whom function of the hydronephrotic kidney never became abnormal and who could not, therefore, have been considered to have obstruction. This retrospective study underlines the importance of performing a randomized prospective study on the value of pyeloplasty in this group of children. PMID- 1880564 TI - Assessment of response to cancer therapy using fluorine-18-fluorodeoxyglucose and positron emission tomography. AB - In order to evaluate the usefulness of 18F-FDG PET in the assessment of therapeutic effects, FDG-PET studies were performed both before and after therapy in 26 patients with miscellaneous malignant tumors. The change in FDG uptake by therapy was compared with the change in tumor size and prognosis. All 26 lesions had a high FDG uptake before therapy. Five of seven lesions which had a relatively low FDG uptake before therapy showed no change or increase in tumor size by therapy. The decreased FDG uptake after therapy was more prominent in the partial response group than in the no change group. FDG uptake before therapy in the non-relapse group was higher than that in the relapse group. However, a decreased FDG uptake did not necessarily indicate a good prognosis. One patient with no change in tumor size and a decreased FDG uptake had no recurrence. This suggests that FDG-PET has a complementary role in the assessment of therapeutic effects. PMID- 1880565 TI - Estimates of radiation absorbed dose for intraperitoneally administered iodine 131 radiolabeled B72.3 monoclonal antibody in patients with peritoneal carcinomatoses. AB - Using a newly available model for determining estimates of radiation absorbed dose of radioisotopes administered intraperitoneally, we have calculated absorbed dose to tumor and normal tissues based on a surgically controlled study of radiolabeled antibody distribution. Ten patients with peritoneal carcinomatosis received intraperitoneal injections of the murine monoclonal antibody B72.3 radiolabeled with 131I. Biodistribution studies were performed using nuclear medicine methods until laparotomy at 4-14 days after injection. Surgical biopsies of normal tissues and tumor were obtained. The marrow was predicted to be the critical organ, with maximum tolerated dose [200 rad (2 Gy) to marrow] expected at about 200 mCi (7.4 GBq). In patients with large intraperitoneal tumor deposits, the tumor itself is an important source tissue for radiation exposure to normal tissues. Local "hot-spots" for tumor-absorbed dose were observed, with maximum tumor-absorbed dose calculated at 11,000 rad (11 Gy) per 100 mCi (3.7 GBq) administered intraperitoneal; however, tumor rad dose varied considerably. This may pose serious problems for curative therapy, especially in patients with large tumor burdens. PMID- 1880566 TI - Comparison of oral iodine-131-cellulose and indium-111-DTPA as tracers for colon transit scintigraphy: analysis by colon activity profiles. AB - In 11 normal subjects and 11 patients with a clinical diagnosis of constipation, oral 131I-cellulose and 111In-DTPA were compared simultaneously as tracers for radionuclide colon transit scintigraphy. Visual assessment of the images revealed no differences between tracers. Quantitation was performed using total and segmental percent retention and the derived value of clearance half-time. In addition, profiles of the activity distribution along the length of the colon were generated and the mean position of the activity in the colon calculated. For all indices, the results were similar in both normal subjects and constipated patients when comparing tracers, although marked differences were present between normal subjects and constipated patients for each tracer. Indium-111-DTPA was easy to administer and dosimetry was more acceptable than for 131I-cellulose, especially in constipated patients. It is concluded that 111In-DTPA is the preferred tracer for oral colon transit scintigraphy. PMID- 1880567 TI - Technetium-99m-d,1-hexamethylpropyleneamine oxime (HMPAO) uptake and glutathione content in brain tumors. AB - Technetium-d, HMPAO SPECT was performed in 70 patients suffering from intracerebral tumors of various histologic types (glioma n = 30, meningioma n = 19, metastases n = 10, angioma n = 3, neuroma n = 2, lymphoma n = 2, neurocytoma n = 1, epidermoid n = 1, gliosis n = 1, cholesteatoma n = 1). Tumor classification was histologically verified in all subjects except in two cases with inoperable angiomas. SPECT was performed under resting state conditions with a dual-head rotating camera (SIEMENS ZLC 37) following intravenous injection of 18-25 mCi 99mTc-d, 1-HMPAO. Regional tracer deposit was expressed in terms of a cerebellar index (CBI). Significantly higher regional HMPAO uptake was found in meningiomas when compared with gliomas of different malignancy (ANOVA p less than 0.05). Within gliomas, regional uptake increased with malignancy (n.s.). In 23 patients, a total of 32 tumor specimens were obtained for histochemical analysis of glutathione (GSH) content using high-pressure liquid chromatography. A significant correlation (least square method, p less than 0.001) between CBIs and GSH values was found, supporting the hypothesis that GSH is the predominant factor for the conversion of the lipophilic complex to hydrophilic derivates. PMID- 1880568 TI - Technetium-99m-HMPAO retention and the role of glutathione: the debate continues. PMID- 1880569 TI - An analysis of cerebral blood flow in acute closed-head injury using technetium 99m-HMPAO SPECT and computed tomography. AB - Technetium-99m-hexamethylpropyleneamine (HMPAO) SPECT and x-ray CT were compared in 15 patients with acute closed-head injury. There were 44 focal lesions in all. Fifteen (34%) lesions were seen on both x-ray and SPECT. Seventeen (39%) lesions were seen only on SPECT. Twelve (27%) of the lesions were seen on x-ray tomography only. Of the lesions seen on x-ray tomography but not on SPECT, two were subarachnoid hemorrhage, two were thin subdural hematomas, and eight were contusions. This study shows that SPECT can detect focal disturbances of cerebral blood flow that are not seen on x-ray tomography. It also suggests that there are two types of contusions: those with a decreased cerebral blood flow (i.e., detectable on SPECT) and those with a cerebral blood flow equal to that of the surrounding brain. PMID- 1880570 TI - Visual and quantitative analysis of interictal SPECT with technetium-99m-HMPAO in temporal lobe epilepsy. AB - Interictal 99mTc-HMPAO SPECT images were compared to ictal EEG localization in 51 patients with intractable temporal lobe epilepsy to determine their usefulness for preoperative seizure focus localization. Both quantified temporal lobe asymmetry and blinded visual detection of temporal lobe hypoperfusion were employed. Visual analysis detected ipsilateral hypoperfusion in 18 (39%) of the 46 patients with a unilateral focus and contralateral hypoperfusion in 3. None of the five patients with bitemporal foci had unilateral hypoperfusion. The positive predictive value of unilateral temporal lobe hypoperfusion was 86% (18/21). Quantified anterior temporal lobe asymmetry, greater than a previously derived normal range, correctly identified the focus in 22 (48%) but gave the wrong side in 5, resulting in a predictive value of 81%. The degree of asymmetry correlated inversely with age of seizure onset, but not with other clinical parameters, histology, or verbal and nonverbal memory. The usefulness of interictal 99mTc HMPAO SPECT for pre-operative seizure focus localization is limited by low sensitivity when performed with a conventional rotating gamma camera. This suggests that ictal or immediate postictal imaging may be necessary for this purpose. PMID- 1880571 TI - Cholecystokinin cholescintigraphy: detection of abnormal gallbladder motor function in patients with chronic acalculous gallbladder disease. AB - CCK cholescintigrams were performed in 374 patients with recurrent postprandial right upper quadrant pain, biliary colic, and a normal gallbladder sonogram and/or cholecystogram. The results of these examinations were correlated with the patients' final medical/surgical diagnoses. Twenty-seven patients recruited as control volunteers without objective clinical evidence of biliary disease also underwent CCK cholescintigraphy to determine if the degree of gallbladder contraction post-CCK differs in symptomatic versus asymptomatic subjects. Decreased gallbladder motor function was identified (maximal gallbladder ejection fraction response to CCK less than 35%) in 94% of patients with histopathologically confirmed chronic acalculous cholecystitis or the cystic duct syndrome and in 88% of patients clinically believed to have chronic acalculous biliary disease. Decreased gallbladder motor function does not distinguish symptomatic from asymptomatic gallbladder disease. PMID- 1880572 TI - Muscle perfusion with technetium-MIBI in lower extremity peripheral arterial diseases. AB - There have been several methods utilized in the diagnosis or assessment of medical or surgical treatments of peripheral arterial diseases. In this study, the diagnostic value of a new tracer: 99mTc-methoxy-isobutyl-isonitrile (MIBI) has been demonstrated in patients with leg claudication. We successively performed muscle perfusion scans in 6 normals and 18 patients with claudication pain during rest and after exercise on the same day. Muscle perfusion abnormalities in all patients were consistent with the defects in the arteries of the affected limbs. The results show that this is a simple and accurate diagnostic procedure and superior to those that have been previously used. PMID- 1880573 TI - Rest-injected thallium-201 imaging for assessing viability of severe asynergic regions. AB - To evaluate the utility of rest-injected 201Tl initial and delayed images for assessing the viability of severe asynergic regions, we studied 17 patients with apparently prior infarcted myocardium in combination with 99mTc ventriculography before and after revascularization. In 51 regions with severe asynergy, the percent 201Tl uptake was calculated as the ratio of counts on the segment with asynergy to the maximum counts on the normal segment. Eleven of 14 regions with resting 201Tl redistribution (Group 1) had improved wall motion after revascularization. However, 14 of 37 regions without redistribution also improved (Group 2). Twenty-three regions without redistribution or improved wall motion after revascularization (Group 3) had lower regional 201Tl uptake on their delayed images than those in Groups 1 and 2. Moreover, the initial regional uptake of Group 2 was higher than that of Group 3. These results suggest that redistribution on rest-injected 201Tl scans indicates reversibility of severely asynergic myocardium and that high 201Tl uptake in regions without redistribution may predict improvement in wall motion after revascularization. We conclude that 201Tl uptake may be useful as a marker of viability of severe asynergic regions before revascularization. PMID- 1880574 TI - Metabolic asymmetries in asymptomatic HIV-1 seropositive subjects: relationship to disease onset and MRI findings. AB - Fifteen male homosexual subjects (mean age 31.6 +/- 7.2 yr) who were asymptomatic, but HIV-1 seropositive (HIV+) were compared to 15 male age-matched HIV-1 seronegative (HIV-) subjects using resting PET/FDG studies and MR scans. Mean cerebral metabolic rates for glucose (mg/100 g/min) in the HIV+ and HIV- subjects were 7.7 +/- 1.7 and 7.0 +/- 2.1, (p = 0.44), respectively. An index of regional metabolic asymmetry for the whole brain was 5.8% +/- 3.2% in the HIV+ and 2.7% +/- 2.3% in the HIV- (p = 0.002), and the difference was most prominent in the prefrontal area. Significant asymmetries were found in 10/15 HIV+ subjects, primarily in prefrontal (7/15) and premotor (4/15) regions. MRI scans showed no abnormalities on clinical or quantitative evaluation in HIV+ subjects. Upon follow-up of HIV+ subjects over 18-40 mo, seven became symptomatic, of which two died. There was no relationship between the presence of PET scan abnormalities and earlier onset of symptomatic disease. PMID- 1880575 TI - Positron-labeled angiotensin-converting enzyme (ACE) inhibitor: fluorine-18 fluorocaptopril. Probing the ACE activity in vivo by positron emission tomography. AB - To evaluate the feasibility of probing the distribution of angiotensin-converting enzyme (ACE) in vivo using positron emission tomography (PET), 4-cis [18F]fluorocaptopril (18FCAP) was prepared by the reaction of the triflate 2 with K18F/Kryptofix 222 in MeCN followed by hydrolysis (2 N NaOH). The synthesis time was 1 hr with an average radiochemical yield (EOS) of 12% and a specific activity of greater than 300 Ci/mmol. In vivo biodistribution in rats at 30 min after administration showed high uptakes into organs known to have high ACE concentration (lung, kidney and aorta) and faster clearance of 18FCAP for lung and kidney, compared to the clearance from the aorta. When different amounts of unlabeled 4-cis-fluorocaptopril (SQ 25750) were coinjected in rats, a dose of greater than 5 micrograms/kg decreased the lung uptake by one-half while only 1 microgram/kg decreased the kidney uptake by one-half. In general, the binding in the four tissues studied was saturable with the expected capacity. 18FCAP was administered to a human and displaceable uptake observed in the lung and kidney. The results demonstrate the feasibility of probing ACE in vivo using PET. PMID- 1880576 TI - Brief inhalation method to measure cerebral oxygen extraction fraction with PET: accuracy determination under pathologic conditions. AB - The initial validation of the brief inhalation method to measure cerebral oxygen extraction fraction (OEF) with positron emission tomography (PET) was performed in non-human primates with predominantly normal cerebral oxygen metabolism (CMRO2). Sensitivity analysis by computer simulation, however, indicated that this method may be subject to increasing error as CMRO2 decreases. Accuracy of the method under pathologic conditions of reduced CMRO2 has not been determined. Since reduced CMRO2 values are observed frequently in newborn infants and in regions of ischemia and infarction in adults, we determined the accuracy of the brief inhalation method in non-human primates by comparing OEF measured with PET to OEF measured by arteriovenous oxygen difference (A-VO2) under pathologic conditions of reduced CMRO2 (0.27-2.68 ml 100g-1 min-1). A regression equation of OEF (PET) = 1.07 x OEF (A-VO2) + 0.017 (r = 0.99, n = 12) was obtained. The absolute error in oxygen extraction measured with PET was small (mean 0.03 +/- 0.04, range -0.03 to 0.12) and was independent of cerebral blood flow, cerebral blood volume, CMRO2, or OEF. The percent error was higher (19 +/- 37), particularly when OEF is below 0.15. These data indicate that the brief inhalation method can be used for measurement of cerebral oxygen extraction and cerebral oxygen metabolism under pathologic conditions of reduced cerebral oxygen metabolism, with these limitations borne in mind. PMID- 1880577 TI - Gamma imaging with negatively charge-modified monoclonal antibody: modification with synthetic polymers. AB - Antimyosin Fab has been modified to carry highly negatively charged synthetic polymers containing DTPAs (DTPA-PL) as chelating agents, of starting molecular weights 3.3 and 17 kD. The immunoreactivities of the modified antibodies were unaffected by the modification procedure. The isoelectric points (PI) of unmodified antimyosin (AM) Fab (PI range 7-9, Mr = 52kD) were changed to PIs predominantly between 4 and 5 (Mr = 59 kD for DTPA-PL3.3kD-AM-Fab and 67kD for DTPA-PL17kD-AM-Fab). These AM-Fab preparations were tested for specific target localization and visualization in vivo in an experimental canine model of acute myocardial infarction. The charge-modified 111In-labeled AM-Fab preparations showed enhanced target (necrotic myocardium) visualization within 30 min of intravenous infusion and decreased background activity in normal myocardium (mean %ID/g +/- s.e.m., 0.0076 +/- 0.0006, n = 164, and 0.0056 +/- 0.0004, n = 92, for 111In-DTPA-PL3.3kD- and DTPA-PL17kD-AM-Fab respectively) relative to conventional 111In-DTPA-AM-Fab (0.0263 +/- 0.0037, n = 135) (p less than 0.001) or radioiodinated AM-Fab (0.0098 +/- 0.0006, n = 256) (p less than or equal to 0.001). Furthermore, the concentration of negatively charged 111In-labeled antimyosin Fab decreased in non-target organs such as the liver and kidneys. In diagnostic and therapeutic applications, charge-modified macromolecules may improve target localization and reduce non-target organ activity. PMID- 1880578 TI - Optimizing antibodies for use in nuclear medicine. PMID- 1880579 TI - Radioiodinated 1-(5-iodo-5-deoxy-beta-D-arabinofuranosyl)-2-nitroimidazole (iodoazomycin arabinoside: IAZA): a novel marker of tissue hypoxia. AB - 1-(5-Iodo-5-deoxy-beta-D-arabinofuranosyl)-2-nitroimidazole (IAZA) has been synthesised and labeled with 125I. Radioiodinated IAZA was shown to undergo hypoxia-dependent binding in EMT-6 cells in vitro and to have an initial binding rate of 284 pmole/10(6) cells/hr at a substrate concentration of 30 microM. This binding rate is more than three times that of the reference compound, misonidazole (89 pmole/10(6) cells/hr). The elevated binding rate was accompanied by in vitro cytotoxicity 30-40 times greater than that observed for misonidazole. Whole-body elimination and biodistribution studies in BALB/c mice bearing implanted, subcutaneous EMT-6 tumors showed a rapid excretion (greater than 98% in 24 hr) with moderate tissue levels which, in general, declined as a function of blood clearance. Tumor-to-blood ratios of 4.6 (4 hr) and 8.7 (8 hr), with respective tumor uptake values of 2.08% and 1.22% ID/g of tissue, form a rational basis for evaluation of this and related 2-nitroimidazole analogs as radiopharmaceuticals suitable for scintigraphic evaluation of tissue (tumor) hypoxia. PMID- 1880580 TI - An investigation of the magnitude and causes of count loss artifacts in SPECT imaging. AB - A quantitative evaluation and an investigation of the mechanism of the count losses that can occur in SPECT imaging is described. The most common clinical example of the artifacts which result from this is encountered when sections are taken through the femoral heads in skeletal studies of the pelvis. From some simple phantom studies, it was identified that the count losses were associated with the presence of a high dynamic range in the projection data. Further information was obtained from simulation studies. It was found that the count loss phenomenon is caused by the combined effects of the presence of a high count density area and a structure with a relatively high attenuation level. An appreciation of the presence, magnitude, and mechanism of this effect is important if erroneous clinical findings are to be avoided. This is particularly relevant because of the existence of a variety of techniques that can be used to remove the resulting artifacts. PMID- 1880581 TI - Isotopic findings in anomalous origin of the left coronary artery from the pulmonary artery: report of an adult case. AB - Anomalous origin of the left coronary artery from the main pulmonary trunk results in myocardial ischemia or infarction, and may be a cause of death in the first months of life. Some patients, however, develop satisfactory coronary collateral circulation and remain asymptomatic into adulthood. In these patients, myocardial perfusion and left ventricular function are not well understood. We report the case of a 17-yr-old female patient, suffering from anomalous origin of the left coronary artery from the main pulmonary trunk, who underwent reimplantation of the left coronary artery to the aorta. The preoperative permanent 201Tl defect of the left antero-lateral ventricular wall and the abnormal regional wall motion induced by stress exercise testing were fully reversed after the operation. PMID- 1880582 TI - Gallium-SPECT in the detection of prosthetic valve endocarditis and aortic ring abscess. AB - A 52-yr-old man who had a bioprosthetic aortic valve developed Staphylococcus aureus bacteremia. Despite antibiotic therapy he had persistent pyrexia and developed new conduction system disturbances. Echocardiography did not demonstrate vegetations on the valve or an abscess, but gallium scintigraphy using SPECT clearly identified a focus of intense activity in the region of the aortic valve. The presence of valvular vegetations and a septal abscess was confirmed at autopsy. Gallium scintigraphy, using SPECT, provided a useful noninvasive method for the demonstration of endocarditis and the associated valve ring abscess. PMID- 1880583 TI - Reorientation of the left ventricular long-axis on myocardial transaxial tomograms by a linear fitting method. AB - A method is described for reorientating the left ventricular (LV) long-axis from myocardial transaxial tomographic data. On a midventricular transverse slice and on a midventricular sagittal slice, the apical and basal limits are selected successively by the operator. The linear activity profiles between these two limits are plotted line by line. In each profile, the two points with the maximum counts in the septal and lateral walls on the transverse slice, or in the anterior and inferior walls on the sagittal slice, are detected. The intermediate point with the minimum counts is then determined. The set of points with minimum counts are fitted by a straight line using the least squares method. This line is taken as the LV long-axis. In a series of 15 cases with stress-delayed 201Tl SPECT, the reproducibility of the reorientation with this semi-automatic method was compared with manual selection of the LV long-axis. In all patients, a successful reorientation was obtained with the present method. The reproducibility was significantly better with the semi-automatic method than with the manual selection of the LV long-axis. PMID- 1880584 TI - A theoretical comparison of first-pass and gated equilibrium methods in the measurement of systolic left ventricular function. AB - First-pass and gated equilibrium radionuclide studies of left ventricular function have proven extremely useful in the detection and management of patients with heart disease. Despite this practical experience, however, comparison of these methods generally has been confined to procedural differences that do not reflect the intrinsic properties of the methods. Here, we describe the results of a simple theoretical calculation from first principles that compares the methods based on their relative statistical precision. This analysis assumes that each procedure is carried out with the same tracer dose in the same hypothetical patient under identical conditions and with the same ideal imaging equipment. Results obtained with this model suggest that the imaging time required for a gated equilibrium study to achieve the same statistical precision as a first-pass study is typically less than 2 min in resting subjects and less than 1 min during stress. The analysis also indicates that gated equilibrium studies will tend to possess the greater statistical precision when cardiac output is elevated, such as when the heart is imaged during exercise. On the other hand, this analysis indicates that the first-pass method will tend to possess the greater precision when cardiac output is low and when imaging time is highly constrained. PMID- 1880585 TI - Cone-beam transmission computed tomography for nonuniform attenuation compensation of SPECT images. AB - This paper develops and tests cone-beam transmission computed tomography (CB-CT) for attenuation compensation of SPECT images. CB-CT was implemented on a rotating gamma camera with a point source (1-2 mCi) of 99mTc, and a light-weight aluminum source holder. A cone-beam collimator may be used but is not required. Since the point source is either located at the collimator focal point, or the camera is uncollimated, CB-CT has excellent sensitivity (at least 150 times that of a parallel-hole, high-resolution collimator). The predicted resolution is equal to the intrinsic gamma camera resolution (3-4 mm), which is much higher than for a high-resolution, parallel-hole collimator (10-20 mm). In the present study, CB-CT provided low noise, high-resolution attenuation maps for use in a nonuniform attenuation-weighted backprojection algorithm. The attenuation compensation accuracy was tested using basic geometries of line sources and nonuniform density models. For the appropriate scaling of the attenuation map, the attenuation compensation was accurate and removed the SPECT image distortion associated with nonuniform attenuation. Attenuation maps acquired either with cone beam collimator or without any collimator were both successful. Using CB-CT, SPECT can thus be made much more accurate without adding unduly to the imaging time, complexity, or cost. PMID- 1880586 TI - Simplified methods for renal clearance in children: scaling for patient size. AB - Development and validation of simplified renal clearance methods has required a research data base of multiple blood samples drawn over a substantial time interval, which is difficult to obtain for children. While the medical risks entailed in drawing multiple samples may be negligible, the problems of parental and institutional consent make such studies more difficult in the pediatric population. Scaling for patient size permits combining data from patients of different age and limits the number of studies required. A scaling technique is presented and evaluated here. With scaling, adult data can be used successfully to predict pediatric responses and to develop pediatric methods based on adult data alone. Inclusion of pediatric data improves the fit and permits development of generic methods that work with both adults and children. PMID- 1880587 TI - Geography and the human brain: representing the cortex on flat paper. PMID- 1880588 TI - Iodine-131 whole-body scan for post-surgical follow-up of differentiated thyroid carcinoma. PMID- 1880589 TI - Possible links between radioactive discharges and cancer. PMID- 1880590 TI - Three-phase bone scan in muscular sarcoidosis. PMID- 1880591 TI - Gallium-67/stable gadolinium antagonism. PMID- 1880593 TI - ART: Ambiguous Radioimaging Terminology. PMID- 1880592 TI - Nonuniformity in myocardial accumulation of fluorine-18-fluorodeoxyglucose in normal fasted humans. PMID- 1880594 TI - Determination of the physical structure of biological materials at biosensor interfaces by techniques of increasing magnification from microscopic to molecular scale. AB - Chemical selectivity of biosensors is derived from biological materials interfaced to the surface of transducing devices. Molecular recognition events lead to macroscopic function suitable for analytical measurements. The structure function relationships of biochemical species at interfaces must be established to characterize and optimize biosensor operation. The techniques of ellipsometry, fluorescence microscopy, electron microscopy, and scanning tunneling microscopy are used to investigate the structure of monolayers and multilayers of proteins and lipids at interfaces that are prepared by Langmuir-Blodgett techniques and by self-assembly from bulk solution. The relative merits and limitations of the measurement techniques in the determination of aspects of interfacial structure are considered. PMID- 1880595 TI - Tridimensional ultrastructure of perfusion fixed gastrointestinal epithelial cells by high resolution scanning electron microscopy. AB - Improvements in the design of modern scanning electron microscopes (SEM) and new methods of specimen preparation incorporating chemical removal of the cytosol and cytoskeleton, now make it possible to view cells and their organelles in three dimensions (3D) at high magnification. In this experiment, high resolution SEM (HRSEM) utilizing new methods of tissue preparation was used to study the intracellular structures of the mouse ileum. In addition, in vivo intestinal perfusion was used to further enhance cellular preservation. Using these modifications it was possible to visualize, in 3D, the fine structure of intestinal epithelial cells and intracellular organelles such as the nucleus, mitochondria, endoplasmic reticulum, and Golgi complex, as well as microvilli and cell membrane. Whole mitochondria appeared as irregularly shaped organelles which contained tubular cristae. Plate-like cristae were not observed. The brush border was found to be closely packed array of cylindrical projections. The extensive folding and structural intricacy of lateral cell membranes between absorptive cells could only be appreciated by viewing this tissue with 3D HRSEM. The use of HRSEM to study 3D ultrastructure of cells and their organelles will improve our understanding of the structure-function relationships in both the healthy and diseased gastrointestinal tract. PMID- 1880596 TI - The structure of the developing chick retinal pigment epithelium revealed by high resolution scanning electron microscopy. AB - The retinal pigment epithelium (RPE) in the developing eye of chick embryos has been studied during the early stages of development by high resolution scanning electron microscopy (HRSEM). Specimen preparation techniques which involve removal of the cytoplasmic matrix permitted visualization of organelles and other subcellular structures within RPE cells in detail and in three dimensional (3-D) stereo HRSEM. Using this technique, we were able to examine changes in melanosome structures during development and demonstrate that pigmentation in the RPE was present by day 4 of development. RPE plasma cell membranes showed extensive folding of the apical portion of the membrane closest to the developing neural retina by day 9. Examination of RPE photoreceptor junction revealed photoreceptor inner segments by day 6 and an outer segment by day 9. Mitochondria in the RPE were found to contain tubular cristae only. The ultra-structure in 3-D of the Golgi apparatus, smooth and rough endoplasmic reticulum, lysosomes and nuclear chromatin of the RPE, and Bruch's layer was revealed by the HRSEM method. PMID- 1880597 TI - Resolution limit of serial sections for 3D reconstruction of tubular cristae in rat liver mitochondria. AB - Following stereo, high resolution scanning electron microscopy (HRSEM) of various rat tissue mitochondria prepared by mild glutaraldehyde fixation followed by freeze cleavage and extraction of the cytosol (Lea and Hollenberg, 1989a), a new model for the ultrastructure of mitochondrial cristae has been developed (Lea and Hollenberg, 1989b). The cristae mitochondriales, previously considered in most cells to have a shelf like structure, were found in many cell types including hepatocytes by HRSEM to be tubes which spanned the mitochondrial matrix and were continuous with the inner mitochondrial membrane at both ends. Despite computer aided, serial, reconstruction of serial thin sections examined in the transmission electron microscope (TEM), tubular cristae in mitochondria have not been resolved entirely, even though circular cross sectional profiles of cristae have been observed in the TEM. The current study was undertaken to probe this deficiency and to understand its cause. In this study, the problems of inherent contrast and resolution loss in the digitized image have been reduced by using a computer based, background, extraction process analogous in the computer to the chemical cytosol extraction process used for HRSEM (Lea and Hollenberg, 1988; Hollenberg et al., 1989). Despite the use of this membrane enhancement algorithm, it was still not possible to reconstruct entire tubular cristae, as observed by HRSEM, even when the micrograph negatives were digitized and reprocessed (Lea and Hollenberg, 1989b). A comparison of serial section thickness deduced from the diffraction colour of the respective section (60 nm) to the measured diameter of tubular cristae profiles (30 nm), with membrane thickness of 10 nm, suggested that this size disparity is responsible for the apparent loss of resolution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880598 TI - A new computer-assisted three-dimensional reconstruction method provides accurate measurement of glomerular mesangial volume. AB - Many glomerulopathies are characterized by progressive mesangial (interstitial) expansion which can be quantitated by morphometric analysis. The purpose of this study was to analyze mesangial and glomerular volumes using a new computer assisted reconstruction (CAR) method. CAR was compared to two standard planar methods, point-counting and linear integration, for accuracy and time efficiency. In Phase I of the study, a computer-based model of the mesangial space was created by placing spherical and ellipsoidal objects of known volume into an enclosing volume mimicking the glomerulus. The simulated mesangium occupied approximately 10 percent of the glomerular volume. The model glomerulus was sectioned serially into ten sections of equal thickness and the three morphometric methods applied to determine the mesangial/glomerular volume. The complexity of the mesangial model was varied by increasing the number of mesangial regions from one to ten to 100. The CAR method estimated the model mesangial volume more accurately (1-9 percent error) through each level of complexity compared to point-counting (3-17 percent error) and linear integration (3-18 percent error). The point-counting method consistently overestimated (P less than 0.05) the fractional mesangial volume for the ten- and 100-region mesangium models. In Phase II of the study, a normal rat glomerulus was sectioned serially (215 sections) and a transmission electron micrograph (TEM) of every fifth section (n = 43) was obtained. Each TEM image (2% of glomerular surface) was digitized for analysis by CAR. Point-counting and linear integration were also performed on the whole glomerular TEMs (n = 10, randomly chosen). The estimated relative mesangial/glomerular volume was 6.6 +/- 0.1 percent by CAR (mean +/- SD), 9.7 +/- 1.5 by linear integration, and 14.9 +/- 3.4 by point counting. The point-counting method was most efficient, requiring 40 +/- 8 sec/section, followed by CAR at 85 +/- 24 sec/section. Linear integration was least efficient (93 +/- 23 sec/section). We conclude that CAR is the most accurate morphometric method of the three compared for estimating mesangial and glomerular methods, although it is more time consuming than the point-counting method and requires more complex instrumentation. CAR is the only method that will analyze the shape and three-dimensional complexity of glomerular structures using TEMs. PMID- 1880599 TI - Image analysis of mineralized and non-mineralized type I collagen fibrils. AB - Turkey leg tendons at an early stage of mineralization have been thin sectioned and imaged by electron microscopy. At this stage collagen-associated mineral apatite was found to be present within both the gap and overlap zones. The earliest apatite occurs in a microcrystalline form which gives a rather generalized and characteristic density to both the gap and overlap zones; with subsequent development larger defined apatite crystals arise which span gap/overlap zones. Fourier transformation of such images revealed the major 67 nm axial repeat of the gap/overlap zone plus four other maxima corresponding to repeat spacings of 22, 16, 13, and 11 nm respectively. Computer imaging techniques were used to reconstruct images by using selected spatial frequencies from such transforms. In this manner the subperiodic distributions of mineral were visually enhanced. These subperiodicities are positioned in an asymmetric fashion over the entire D unit repeat aligning with the molecular orientation of the fibril. Analyses of both negatively stained collagen and computer-generated maps of collagen hydrophobicity were compared to the mineral distribution of collagen. Densitometric comparisons showed a positional correlation between the axial banding patterns of mineralized fibrils and those of negatively stained non mineralized fibrils. Comparable spatial frequencies were also present in transforms between hydrophobic maps and mineral distribution of collagen. These results suggest that the lateral clusterings of hydrophobic residues which span the fibril at specific sites in both the gap and overlap zones serve to prohibit early mineral deposition. This observed hydrophobic influence in combination with the gap space appear as contributing factors in the observed axial distribution of mineral within collagen. PMID- 1880600 TI - A fast image simulation technique for high resolution electron microscopy with multicomponent atomic species. AB - A new method has been developed for simulating high resolution electron microscope images of weak phase objects via a digital television frame store system and fast Fourier transforms of a graphical representation of structures containing several atomic species. Here masks are constructed which consist of circular disk regions whose areas are proportional to the scattering power of the different atom types. These masks represent the object transmission function. The method extends the previous work on image computations of monatomic species objects using small point-like model representations of atom positions. Several examples will be given to verify the relative scattering power from masks corresponding to different atomic species such as Y, Ba, Cu, and O, as well as the limitations of this method for representing objects. Image simulations, which are in agreement with experiments, will also be presented for superconducting oxide materials of the form YBa2Cu3O7 using the circular disk method. PMID- 1880601 TI - A study of protein A-gold resolution for immunoelectron microscopy. AB - For the purpose of investigating a topographical correlation between antigen molecules and protein A-gold(PAG) particles which localized as an immunocytochemical probe, the simplest model on a localization pattern of antigen molecules, which were arranged two-dimensionally on a plane surface of the resin, was used. Ultrathin sections of a G-actin layer, which was adsorbed on epoxy resin and was re-embedded subsequently in JB-4 resin, was stained indirectly with rabbit anti-actin antibody and subsequently by PAG. From this immunoelectron microscopy, a histogram (relative frequency, denoted by y vs. relative length, denoted by x) was obtained using a computer-assisted method. For this histogram, a fitting curve was calculated by a least squares optimization and three parameters (H, U, and W) of the curve which could be useful for a study on the topographical organization of antigen molecules were estimated. Parameter H (maximum y of the curve) would reflect the maximum amount of epitopes at x = U. Half width W, which is the width of the curve at y = H/2, would reflect a breath of epitope masses. This fitting curve was separated into two overlapping curves whose Ws were different from each other. The one constituent curve of which value W was smaller than the other was regarded as a unit curve and the other constituent curve could be resolved into many unit curves whose W values are the same. From these unit curves, the resolution power of the immunoelectron microscopy, using a post-embedding procedure of ultrathin sections, was estimated as 58-66 A degrees. PMID- 1880602 TI - Similar features in Z bands of both skeletal and cardiac muscle revealed by image enhancement. AB - We have shown previously that the small square (ss) and basket weave (bw) states of the Z band lattice in cardiac and skeletal muscle are related to the contractile state of the muscle. We have used two-dimensional image processing techniques on digitized electron micrographs to enhance the structural features of each projected lattice form in cardiac and skeletal muscle. Four different processing techniques were employed to assess the effect of enhancement artifacts on the resulting Z band images. We observed only slight differences between enhanced images of a particular Z band form produced by the four different techniques. Every enhanced image showed an approximate four-fold symmetry independent of muscle type or Z band lattice form. Each enhanced image showed four cross-connecting Z-filaments which appeared to connect each axial filament to the four nearest axial filaments. In bw images from both cardiac and skeletal muscle, axial filaments had a greater apparent diameter and a greater interaxial filament spacing than in the ss images. In both muscle types, the cross connecting Z-filaments appeared to overlap half-way between axial filaments in the ss images while the bw images showed no such overlap. These structural features are consistent with a dynamic Z band lattice that participates in muscle contraction. PMID- 1880603 TI - The use of freeze-substitution and LR gold in the study of rye grass (Lolium perenne) pollen. AB - Pollen grains of Lolium perenne (rye grass) were prepared for transmission electron microscopy by rapid freezing in liquid propane, substitution in acetone, methanol or diethyl ether, and embedment in the acrylic resin London Resin gold. These were compared to pollen chemically fixed (CF) in aldehyde/osmium tetroxide and embedded in the epoxy resin Quetol 651. Ultrastructural preservation was superior in freeze-substituted (FS) pollen, particularly with the use of acetone or methanol. Optimally preserved FS pollen displayed a homogeneous aspect of the cytoplasm and nucleoplasm, and smooth, uninterrupted contour or organelles. A striking difference was also seen in the preservation of inclusions in the intine. Varied forms and sizes of intine inclusions were evident in FS pollen but these were not discernible in the CF image. The FS scheme studied here presents enormous potential for both ultrastructural and immunolabelling studies in rye grass pollen. Problems discussed include artifacts associated with each of the substitution solvents used, and a gradient of freezing damage observed within the pollen grain. PMID- 1880604 TI - A technique for the preparation of cross-sectional TEM samples of ZnSe/GaAs heterostructures which eliminates process-induced defects. AB - Cross-sectional transmission electron microscopy (TEM) sample preparation of ZnSe/GaAs epitaxial films is investigated. Conventional argon ion milling is shown to produce a high density (approximately 5-8 x 10(11)/cm2) of small (diameter approximately 60-80 A) extended defects (stacking faults, microtwins, double positioning twins, etc.). In addition, transmission electron diffraction results indicate a thin ZnO layer can also occasionally form upon ion milling or electron-beam irradiation although the exact conditions for ZnO formation are not well understood. Conventional TEM (amplitude contrast) and high-resolution TEM (phase contrast) imaging in combination with transmission electron diffraction studies were performed to determine the optimum method of removing the ion milling related damage and ZnO layers during sample preparation. HF/HCl, NaOH/H2O, H2SO4/H2O2/H2O and Br2/CH3OH etching mixtures as well as low voltage argon or iodine ion milling were studied. A low energy (2 keV) iodine or argon ion milling step was shown to remove the ZnO layer and reduced the density of the extended defects associated with Ar+ ion milling, but was unsuccessful in removing all of the defects. Auger electron spectroscopy results indicate residual iodine was either left on the surface or implanted beneath the surface during iodine ion milling. Etching the XTEM samples in HF/HCl was shown to be effective in removing the ZnO layer but had little or no effect on the ion milling induced defects. Etching the samples in a 0.5% Br2/CH3OH solution resulted in complete elimination of the ion milling induced extended defects including the residual defects associated with iodine ion milling. In addition the Br2/CH3OH etch produced the best surface morphology. Thus a brief (1-2 seconds) Br2/CH3OH etch after conventional preparation (argon ion milling) of cross-sectional ZnSe/GaAs TEM samples appears to be an inexpensive and superior alternative to iodine ion milling. PMID- 1880605 TI - Simple method for the preparation of InP based samples for TEM investigation. AB - A novel, rapid, and simple method is described for the preparation of InP based samples for investigation by transmission electron microscopy (TEM). The key feature of the technique is Ar+ ion bombardment in an iodine ambient. Cross sectional micrographs of Au/InP samples are shown as an example. The technique developed produces a large area of transparent region. PMID- 1880606 TI - Hugh Sinclair (1910-1990). PMID- 1880607 TI - Diseases of civilisation and EFA. PMID- 1880608 TI - Modulation of lipid chylomicron-synthesizing enzymes in rats by the dietary (n 6):(n-3) fatty acid ratio. AB - The effect of diets with various (n-6):(n-3) polyunsaturated fatty acid (PUFA) ratios and a constant polyunsaturated: saturated fatty acid ratio on the basal activity of chylomicron lipid synthesizing enzymes was investigated in rat intestinal microsomes. Enzymes studied were: acyl-CoA:cholesterol acyltransferase (ACAT); acyl-CoA:lysophosphatidylcholine acyltransferase (MGAT) and acyl-CoA:1,2 diacylglycerol acyltransferase (DGAT). Results showed that after a 4-wk feeding period, ACAT, ACLAT and DGAT basal activities were significantly enhanced by the dietary fatty acids of the (n-3) series, whereas MGAT activity was not affected. When the highest (n-6):(n-3) ratio (51.0) was compared with the lowest (0.8), the increase attained was about 58, 76 and 73% for ACAT, ACLAT and DGAT, respectively. Fatty acid composition of microsomal lipids was drastically altered by the diets because (n-3) PUFA replaced the (n-6) series as the dietary (n-6):(n 3) ratio was lowered. These compositional changes could explain the observed modification in the membrane-bound enzyme activities. We suggest that (n-3) PUFA ingestion leads to an enhanced velocity of chylomicron synthesis in rats. PMID- 1880609 TI - Interrelationship of plasma triglycerides and HDL size and composition in rats fed different dietary saturated fats. AB - We investigated the relative effects of different dietary saturated fats on the size distribution, apolipoprotein (apo) and chemical composition of HDL in fasted rats. Male Sprague-Dawley rats (174 +/- 2 g) were fed diets containing 0.035% cholesterol and 16% fat (wt/wt) from corn oil (CO diet) or from 2% CO plus 14% butterfat (BF diet), beef tallow (BT diet), palm oil (PO diet) or coconut oil (CN diet) for 6 wk. Apparent lipid digestibility was significantly lower with the PO and BT diets vs. the CO, BF and CN diets. Plasma total cholesterol levels were significantly higher in rats fed the PO and BT diets than in rats fed the BF and CN diets but were not different among the PO-, BT- and CO-fed groups. Nondenaturing gradient gel electrophoresis immunoblot analysis indicated that HDL apo A-I and E resided on particles with significantly smaller modal diameters in rats fed all saturated fats compared with those fed the CO diet. Chemical analyses indicated that HDL generally contained proportionately less protein and more triglyceride, free cholesterol and apo E with saturated fat feeding than with CO diet feeding. Significantly higher plasma and VLDL triglyceride levels were noted with ingestion of the BT, PO or CN diet than with the CO diet. Butterfat feeding resulted in lower plasma triglycerides and HDL-esterified cholesterol than did feeding the other saturated fats. Very low density lipoprotein triglyceride concentrations were inversely correlated with HDL modal diameter of apo E containing lipoproteins (P less than 0.005). These data provide further evidence of the interrelationship of triglyceride and HDL metabolism and suggest that mechanisms independent of cholesterol ester transfer protein may mediate this response in rats. PMID- 1880610 TI - Dietary cholesterol and the origin of cholesterol in the brain of developing rats. AB - Milk substitutes containing cholesterol at concentrations lower, equal to or greater than the concentrations found in natural rat milk were fed to artificially reared rat pups from 5 d until 15 or 16 d after birth. Pups reared by their mother served as controls. In one experiment, D7-cholesterol was fed in the milk at four different concentrations. The purpose of the study was to determine whether cholesterol in milk influenced growth and the sterol composition of brain over the period of its most rapid accumulation in this organ. We found that body and brain weights were not different, irrespective of the concentration of cholesterol in the milk substitutes. High concentrations of cholesterol in milk caused a significant increase in cholesterol in liver and plasma, whereas the concentration of cholesterol in brain was not different from the concentration in the brain of controls. The amounts of D7-cholesterol in lung and liver, and in plasma and RBC that pass the brain, were consistent with the concentration fed in the milk and approached 70% of the total content of cholesterol in these organs at the highest concentration fed. Brain, by contrast, contained very small amounts of D7-cholesterol, which could readily be attributed to D7-cholesterol associated with the vascular system of the blood-brain barrier. We found that the sterol composition of brain is not influenced by the concentration of cholesterol in milk and that cholesterol exogenous to brain, even in a hypercholesterolemic condition, does not gain entry to the brain. We conclude that the brain biosynthesizes de novo all the cholesterol it requires. PMID- 1880611 TI - Dietary (n-3) fatty acids affect rat heart, liver and aorta protective enzyme activities and lipid peroxidation. AB - In a 16-wk study, weanling Wistar rats (32 males and 32 females) were fed a modified AIN-76 diet containing 20% fat with various (n-3) fatty acids. All dietary fats provided the same amount of saturates, monounsaturates, and total essential fatty acids [(n-6) + (n-3)]. The control diet contained lard/corn oil (L/CO). The other diets contained (n-3) fatty acids from linseed oil (LSO), from linseed oil + menhaden oil (LSO + MO) or from menhaden oil (MO). The (n-3) diets reduced total and HDL-cholesterol, particularly in rats fed the MO diet. Platelet thromboxane levels were equally depressed by the LSO and MO diets. Dietary (n-3) fatty acids significantly elevated docosahexaenoic acid in livers and hearts of male and female rats, with females reaching higher levels. This increase was accompanied by reduced arachidonic acid, except for hearts of females in which the major decrease was in linoleic acid. Overall, enzyme activities in the MO-fed group were decreased to the following levels (relative to the activity in the control group): heart Mn superoxide dismutase (SOD), 28%; liver CuZnSOD, 82%; aorta CuZnSOD, 32%. Greater reductions in these enzyme activities were seen in the female rats fed the MO diet compared with male rats. Lipid peroxidation, assessed by urinary, heart and liver thiobarbituric acid reactants, was increased by dietary (n-3) fatty acids (MO greater than LSO + MO greater than LSO greater than L/CO) and was higher in females than in males. These results indicate that enhanced lipid peroxidation occurs with the increased oxidative stress of elevated tissue (n-3) fatty acids accompanied by reduced SOD activity. PMID- 1880612 TI - Uptake and metabolism of L-2-oxo-[35S]thiazolidine-4-carboxylate by rat cells is slower than that of L-[35S]cysteine or L-[35S]methionine. AB - The uptake and metabolism of L-2-oxo-[35S]thiazolidine-4-carboxylate (OTC) was compared with that of L-[35S]cysteine and L-[35S]methionine in studies with freshly isolated rat hepatocytes, renal cortical tubules and enterocytes. All three 35S-labeled substrates were metabolized to glutathione, inorganic sulfur and taurine by hepatocytes and to inorganic sulfur by renal tubules and enterocytes. The rate of metabolite production from OTC was always less than 30% of that from cysteine or methionine. The transport rate for uptake of [35S]OTC by hepatocytes was less than that observed for uptake of [35S]cysteine or [35S]methionine. The capacity of rat hepatocytes, renal cortical tubules and enterocytes to take up and metabolize OTC is substantially lower than that for uptake and metabolism of cysteine or its normal intracellular precursor, methionine. PMID- 1880613 TI - Protein deficiency suppresses bone resorption in sheep based on a short-term in vivo bone model. AB - Six sheep were fed protein-deficient and control diets for 40 d for each diet in a crossover design. Each sheep was intramuscularly injected with 120 pmol.d-1.kg body wt-1 of 1,25-dihydroxycholecalciferol during the last 7 d of each dietary period. Approximately 100 mg of bone powder was implanted on the abdominal muscle on d 21 and d 28 of each dietary period. Plaques induced by the bone powder were harvested 12 d after the implantation. Tartrate-resistant acid phosphatase (TR ACP) activity was lower and the number of multinucleated cells was smaller in plaques of animals during the protein-deficient period than during the control period. The administration of 1,25-dihydroxycholecalciferol increased the activity of TR-ACP and the number of multinucleated cells during both dietary treatments. However, TR-ACP activity was still lower and the cell number was still smaller during the protein-deficient period than during the control period when they were injected with 1,25-dihydroxycholecalciferol. These results suggest that protein deficiency reduces the activity of osteoclastic cell induction. The suppressive effect of protein deficiency on the induction and the activity of osteoclastic cells is not related to the action of 1,25-dihydroxycholecalciferol. PMID- 1880614 TI - Glutathione levels and related enzyme activities in vitamin B-6-deficient rats fed a high methionine and low cystine diet. AB - We examined the change in glutathione metabolism in vitamin B-6-deficient rats. Vitamin B-6-deficient rats were fed a vitamin B-6-deficient diet containing 0.56% methionine and 0.075% cystine for 8 wk. Controls were fed an identical diet supplemented with 10 mg pyridoxine hydrochloride/kg diet. Glutathione concentrations in each organ examined were similar in control and vitamin B-6 deficient rats, and the values were comparably lower after intraperitoneal injection of diethylmaleate. However, buthionine sulfoximine caused a significantly greater decrease in glutathione levels in the liver and lungs of vitamin B-6-deficient rats relative to controls. Glutathione peroxidase activity in the liver of vitamin B-6-deficient rats was higher than in control animals; however, glutathione transferase activity in tissues other than liver of vitamin B-6-deficient rats was higher than in the controls. The activities of gamma glutamyl-transferase in the liver and spleen of vitamin B-6-deficient rats were significantly lower than control values. The holoenzyme activities of cystathionine beta-synthase and cystathionine gamma-lyase in the liver of vitamin B-6-deficient rats were markedly reduced. These findings indicate that although the activities of enzymes that synthesize cysteine from methionine were decreased by vitamin B-6 deficiency, the level of synthesis and supply of cysteine in vitamin B-6-deficient rats were sufficient to maintain the same glutathione level as in controls, and that glutathione utilization in the liver was accelerated by vitamin B-6 deficiency. PMID- 1880615 TI - Inhibitory effect of dietary soybean protein vs. casein on magnesium absorption in rats. AB - The effects of casein and soybean protein on magnesium absorption and magnesium concentration in the femur were investigated in rats. Purified diets containing either casein or soybean protein and three concentrations of added magnesium (0.82, 1.64 or 2.46 mmol/100 g diet) were used. The isonitrogenous diets were carefully balanced for the different mineral concentrations in the protein preparations. Absolute and percent magnesium absorption and urinary magnesium excretion were significantly decreased in rats fed soybean protein when compared with casein, irrespective of the dietary concentration of added magnesium. The magnesium content of femur was significantly lower in rats fed soybean protein, but this effect was seen only when the diet contained 0.82 mmol magnesium/100 g diet. The addition of sodium phytate to the casein diets, to a concentration identical to that in the diets containing soybean protein as provided by the soybean protein preparation, produced similar effects on magnesium absorption as the diets containing soybean protein. These results indicate that soybean protein, when compared with casein, decreases magnesium absorption through its phytate component. PMID- 1880616 TI - Calcium, magnesium and phosphorus utilization by rats fed sodium and potassium salts of various inorganic anions. AB - We hypothesized that urinary excretion of calcium would be affected by both urinary excretion of acid and of total fixed anions. Calcium, magnesium and phosphorus utilization was examined in rats fed semipurified diets supplemented with approximately 0.4 mol sodium/kg diet or approximately 0.4 mol potassium/kg diet as chloride, sulfate, bisulfate, carbonate or bicarbonate salts in two studies. The ingestion of supplemental fixed anions (chloride, sulfate or bisulfate) increased urinary excretion of calcium, magnesium and phosphorus. It made no difference whether the anions were ingested as sodium or potassium salts. In Study 1, 80% of the variation in urinary calcium excretion could be explained on the basis of urinary excretion of sulfate, ammonia and total anions. In Study 2, 77% of the variation in urinary calcium excretion could be predicted on the basis of urinary excretion of total anions and sulfate. Although bone and plasma calcium concentrations were not responsive to these dietary changes, less magnesium was retained in bones of rats fed any of the supplemental salts. PMID- 1880617 TI - Intestinal metallothionein gene expression and zinc absorption in rats are zinc responsive but refractory to dexamethasone and interleukin 1 alpha. AB - The effects of dexamethasone and interleukin 1 alpha on intestinal metallothionein gene expression and zinc absorption were studied. Rats given parenteral zinc served as positive controls. A single intraperitoneal or intravenous dose of dexamethasone, interleukin 1 alpha or zinc markedly increased liver metallothionein synthesis 3-9 h after injection. Intestinal metallothionein mRNA and metallothionein protein were not affected by dexamethasone or interleukin 1 alpha, but were markedly increased by parenteral zinc. Absorption of 65Zn from isolated duodenal segments was inversely related to intestinal metallothionein concentration in rats given zinc, but was not affected by dexamethasone or interleukin 1 alpha. Plasma zinc concentrations decreased in rats given dexamethasone or interleukin 1 alpha and increased in those given zinc, but they were not related to 65Zn absorption. Similarly, multiple intraperitoneal administration of either dexamethasone or interleukin 1 alpha, or oral administration of dexamethasone, for 7 d markedly increased liver metallothionein synthesis but did not affect intestinal metallothionein concentration or 65Zn absorption. These results suggest that intestinal metallothionein gene expression and 65Zn absorption are refractory to glucocorticoid hormone and interleukin 1 alpha. PMID- 1880618 TI - Energetic efficiency of rats fed low or high protein diets and grown at controlled rates from 80 to 205 grams. AB - Energetic efficiency of protein and lipid deposition was estimated based on the data from 53 rats fed purified diets. Intercepts of equations relating energy gain to metabolizable energy intake were different (P less than 0.002) for rats fed diets that contained 10 and 20% casein, so that metabolizable energy for maintenance was 118 and 108 kJ/day, respectively. Surprisingly, in view of the supposedly greater efficiency of lipid deposition, energetic efficiency above maintenance was constant at 0.38 +/- 0.02. Part of the reason is that composition of body gain was much less rigidly tied to daily energy intake--even across the wide range of data in this experiment--than is necessary to quantify reliably such an effect. Two methods of quantifying partial energetic efficiencies of protein and lipid deposition gave results that were comparable to previous estimates of about one-third and two-thirds, respectively. One of the methods used a more biological model but failed to fit data for rats fed the 10% casein diet. Because traditional statistical methods are unlikely to be extended much further to account for the many unsolved problems associated with estimating partial efficiencies, systems based at tissue and cellular levels are necessary to model detailed differences in energy utilization. PMID- 1880619 TI - Dietary glucose increases plasma insulin and decreases brown adipose tissue thermogenic activity in adrenalectomized ob/ob mice. AB - The purpose of this study was to determine whether consumption of a high glucose diet would increase plasma insulin concentrations and decrease brown adipose tissue metabolism in adrenalectomized ob/ob mice previously fed a high starch diet. Male sham-operated and adrenalectomized ob/ob and lean mice were fed a high starch diet for 12 d, then switched to a high glucose diet for the last 2 or 4 d of the 14- or 16-d feeding trials. Adrenalectomized ob/ob mice consumed 16% more energy and gained 50% more weight without an increase in oxygen consumption when switched from a high starch diet to a high glucose diet. Within 2 d after the switch to the high glucose diet, plasma insulin concentrations increased by 70% without any change in plasma glucose concentrations; brown adipose tissue metabolism, as assessed by GDP binding to brown adipose tissue mitochondria, was decreased by 26% 4 d after the diet switch. Sham-operated ob/ob and lean mice and adrenalectomized lean mice were minimally affected by the switch to the high glucose diet. The increase in plasma insulin concentrations in adrenalectomized ob/ob mice induced by the high glucose diet may contribute to the observed depression in brown adipose tissue metabolism. PMID- 1880620 TI - Lymphocyte subpopulations in the thymus, lymph nodes and spleen of iron-deficient and rehabilitated mice. AB - Three groups of weanling female mice were fed one of two iron-deficient diets (5 and 12 mg Fe/kg diet) or a normal diet (30 mg Fe/kg diet) for 6 wk. A control pair-fed group was included. Seven mice received the 5 mg Fe/kg diet for 6 wk, then were rehabilitated using the 30 mg Fe/kg diet for 10 d. Mice fed the 5 mg Fe/kg diet were moderately iron-deficient, as shown by indices of iron status. No significant differences were observed in thymus weight or in the proportion and number of thymocyte subsets in thymuses of anemic, moderately iron-deficient and control mice. Thymus weight was decreased in pair-fed mice. No significant difference was found in lymph node subsets. In the spleen of anemic mice, the proportions and total number of Thy-1+ splenocytes, CD4-8+ and CD4+8- cells were very low compared with control (P less than 0.01) and iron-deficient (P less than 0.02) mice. The decrease was not only observed for the percentage of subsets but also for the absolute number of cell subtypes per spleen. Thy-1+ splenocyte subpopulations were normalized after rehabilitation. These quantitative modifications could explain alterations in the blastogenic response of splenic lymphocytes described by other authors. PMID- 1880621 TI - Flow cytometric analysis of the phenotypic distribution of splenic lymphocytes in zinc-deficient adult mice. AB - Many immunodeficiency states create an imbalance in the ratio of T cells to B cells or in the subsets of lymphocytes found within these two major classes. A 30 d period of suboptimal intake of zinc often caused a 50% decrease in the total number of splenic lymphocytes in young adult mice. One- and two-color flow cytometric analysis was made of the residual splenocytes of the zinc-deficient mice to determine whether the deficiency had also altered the composition or phenotypic distribution of any of the major subsets of T cells or B cells. Marginally zinc-deficient mice had a normal ratio of T cells to B cells with no notable change in the subsets of lymphocytes making up these two classes. Severely zinc-deficient mice that exhibited a significant degree of parakeratosis demonstrated a 20% increase in the overall ratio of T helper to T suppressor/cytotoxic cells as well as a modest decline in the percentage of B cells (5-8%). The latter decrease was not in the B cells bearing immunoglobulin M or D but in the minor subsets bearing other immunoglobulin isotypes. Thus it seems that, whereas zinc deficiency caused significant reductions in the total numbers of splenic lymphocytes, it caused no significant change in the composition of the splenic lymphocytes except in the most severe cases. PMID- 1880622 TI - Increased dietary branched-chain amino acids do not improve growth in developing rats with chronic biliary obstruction. AB - We studied dietary branched-chain amino acid enrichment in cholestatic weanling rats. Growth was assessed with body weight, muscle weight and nitrogen balance. Systemic metabolic measurements that reflect liver function were evaluated, including plasma ammonia, albumin, amino acids, glucose, triglyceride and branched-chain ketoacids, as well as urinary carnitine excretion. Twenty-two rats underwent bile-duct ligation at 14 d of age. At weaning, 11 rats were fed a control diet and 11 an isoenergetic, isonitrogenous branched-chain amino acid enriched diet for 3 wk, each with a sham-operated, pair-fed control. Body weights were similar in all four groups. Changes due to bile-duct ligation and not affected by the diet manipulation included lower plasma glucose, nitrogen balance and muscle weight, and higher triglyceride concentration, carnitine excretion and liver weight. Changes due to ligation that were normalized by dietary manipulation included plasma albumin, ammonia and total amino acid concentrations. The ratio of branched-chain to aromatic amino acids was decreased in ligated animals fed both diets; however, branched-chain amino acids were lower in the two groups fed more branched-chain amino acids. PMID- 1880623 TI - Dietary protein level and energy metabolism during treadmill exercise in horses. AB - Six conditioned Quarter Horse mares were used in a crossover design to assess the effect of the dietary protein level on intramuscular and hepatic glycogen and lactate, oxygen uptake and blood lactate, pyruvate and free fatty acids. After a 2-wk adaptation period to either a 9.0% (control) or an 18.5% crude protein diet, each horse performed an exercise test. The horses were exercised for 15 min on an 11% grade treadmill at 4.5 m/sec. The exercise test was performed 3-4 h after a meal. Venous, arterial and mixed-venous blood samples were taken simultaneously at rest and during exercise. Muscle and liver samples were taken at rest and after exercise. The dietary protein level did not affect hepatic or intramuscular glycogen utilization (P greater than 0.05). Exercise resulted in increased (P less than 0.001) lactate in venous blood, muscle and liver; however, dietary treatment did not affect (P greater than 0.05) lactate level. Venous blood lactate:pyruvate ratio was higher (P less than 0.05) in the control horses. Dietary protein level did not affect (P greater than 0.05) oxygen uptake or plasma free fatty acids; however, exercise increased (P less than 0.01) both. These results indicate the dietary protein did not affect substrate utilization during the absorptive phase of digestion in exercising horses; however, the higher lactate:pyruvate ratio in the control horses suggests that the intraconversion of lactate and pyruvate may be influenced by diet composition. PMID- 1880624 TI - Receptor-mediated lipoprotein transport in laying hens. AB - In laying hens, VLDL and vitellogenin (VTG) are secreted by the liver and eventually taken up by the growing oocyte via receptor-mediated endocytosis. Both macromolecules bind to the same receptor, termed the VLDL/VTG receptor, localized on the oocyte plasma membrane. Once taken up by the growing zygote, apolipoprotein B, the major protein constituent of VLDL, is proteolytically cleaved by a chicken-specific cathepsin-D. Systemic cholesterol homeostasis in the chicken is maintained by expressing a different apoprotein B-specific receptor in somatic cells, which in terms of its function is very similar to the mammalian LDL receptor. The phenotype of the Restricted Ovulator hen, characterized by hereditary hyperlipidemia and the absence of egg laying, was identified as a lack of expression of functional VLDL/VTG receptors in the oocytes without affecting somatic apoprotein B receptors. PMID- 1880625 TI - Importance of essential fatty acids and their derivatives in poultry. AB - More than thirty-five years have passed since essential fatty acid requirements were demonstrated for poultry. Subsequent studies were conducted to establish a recommended level of linoleic acid for growing poultry. Although a requirement of 1% linoleic acid is suggested, a critical evaluation of the nutritional and metabolic significance of essential fatty acids is lacking. Perhaps alpha linolenic acid is also essential, but direct evidence is not yet available. Recent literature indicates that several individual fatty acids, including the polyunsaturates derived from essential fatty acids, are biologically active. Furthermore, the numerous eicosanoids biosynthesized from specific polyunsaturates act as either cellular autocrine or paracrine signaling agents. Formation of eicosanoids is ubiquitous in tissues and organs, and these compounds influence nearly all systems in mammalian species. However, although such compounds have been studied extensively in mammalian systems, the formation of polyunsaturates, the biosynthesis of eicosanoids and the biological effects of these compounds have not been intensely studied in domestic poultry. PMID- 1880626 TI - Adipose cellularity in Gallus domesticus: investigations to control body composition in growing chickens. AB - The domestic chicken, Gallus domesticus, is recognized as an efficient source of lean meat. Genetic selection has resulted in large body size strains that grow rapidly. Concomitant with development of these desirable characteristics is increased abdominal fat deposition and altered body composition. Adipose cellular development in different genetic groups shows that abdominal adipocyte cell number as a proportion of body mass decreases as body size increases, concurrent with increased adiposity. Adipocyte hypertrophy explains a large proportion of the variation in abdominal fat percentage. Growth hormone is correlated with the number and size of abdominal adipocytes across genotype, sex and age. Adipose tissue development and body composition are affected by hormone levels in growing chickens. Possible approaches to modulate fat deposition and adipose cellularity in poultry are reviewed. PMID- 1880627 TI - Future directions for the American Institute of Nutrition. PMID- 1880628 TI - Effects of vitamin E on toxicity by minute amounts of paraquat fed continuously to rats. AB - The effects of vitamin E on toxicity by minute amounts of paraquat fed continuously for some period to rats were investigated. Two experiments were carried out as experiments 1 and 2. In both experiments, weaning rats were divided at first into two groups; one group was given a vitamin E-deficient diet, and the other a vitamin E-supplemented control diet (50 mg alpha-tocopherol/kg of diet). They were fed on these diets for 40 days. After that, in both experiments, the rats that had been fed the vitamin E-deficient diet were further divided into two groups, which were either given a paraquat-added diet (+PQ-E) or continuously fed the same vitamin E-deficient diet (-E). The amount of paraquat added was 250 mg of methyl viologen per kg of diet. After the addition of paraquat, these two groups were pair-fed. In experiment 1, paraquat was given to all the rats fed the vitamin E-supplemented control diet (+PQ+E). In experiment 2, rats fed the control diet were divided into paraquat-added (+PQ+E) and non-paraquat-added (+E) groups, similar to those of vitamin E-deficient rats. These two groups were also pair-fed thereafter. In both experiments, about 35 days after paraquat addition, they were sacrificed. Plasma and liver alpha-tocopherol contents were measured by HPLC, and liver peroxidation value was measured by chemiluminescence and the TBA method. And, as parameters of vitamin E deficiency, plasma pyruvate kinase and GOT activities and alpha-cysteine proteinase inhibitor (alpha-CPI) level were measured. When the analyzed values were compared between paraquat-added and the corresponding not-added control groups (+PQ-E vs. -E, +PQ+E vs. +E), the following results were obtained. In experiment 1, the values of plasma and liver alpha-tocopherol levels were significantly lower in the +PQ-E group than those of the -E group; however, liver peroxidation values and values of the three parameters of vitamin E deficiency were not different significantly. In experiment 2, the value of liver alpha-tocopherol level was significantly lower in the +PQ+E group than that of the +E group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1880629 TI - Binding form of vitamin B2 in bovine milk: its concentration, distribution and binding linkage. AB - The contents of total, free, and bound vitamin B2 (B2) in bovine milk and their distribution in four separate milk fractions, including milk during the early lactation stage, were estimated. The total B2 content in whole mature milk was 179 +/- 25 micrograms/100 g (n = 16), and its distribution in the cream, whey, skim milk membrane, and casein fractions was 6, 67, 9, and 18%, respectively. The amount of flavins bound to protein in the total B2 was 13.6% in whole milk and rich in membrane fraction. The total B2 content (micrograms/100 g of milk) was higher in colostrum at 1-3 days (287 +/- 120) than in colostrum at 4-7 days (173 +/- 27), in transitional milk (182 +/- 33), and in mature milk (179 +/- 44). The bound flavin content decreased slightly as lactation progressed (20-30 micrograms/100 g), but the ratio of bound/total B2 did not vary (12-15%). Milk fat globule membrane (MFGM) contained 414 +/- 65 micrograms of B2/g of protein, most of it being bound to protein (92%). Market milks contained as much total B2 as raw whole milk, but the amount of bound form was only 2%. Guanidine HC1, urea, sodium dodecyl sulfate, pH at 3.0-3.5, delipidation, and boiling released most of the B2 bound to protein, suggesting that bound flavins bind to milk proteins by a hydrophobic linkage. PMID- 1880630 TI - Effects of dietary fat and protein on the activity of alpha-amino-beta carboxymuconate-epsilon-semialdehyde decarboxylase and the urinary excretion of niacin metabolites in rats. AB - The effects of dietary protein and soybean oil on the metabolism of L-tryptophan through the NAD pathway and the activity of alpha-amino-beta-carboxymuconate epsilon-semialdehyde decarboxylase (ACMSD) [EC4.1.1.45] in rat liver and kidney were investigated. The animals were fed on the following niacin-free diets for 11 days: group 1, a fat-free 20% casein diet (20% Cas); group 2, a fat-free 40% casein diet (40% Cas); group 3, a 40% casein diet containing 20% soybean oil (40% Cas + 20% F). After feeding on each diet for 7 days, the urine was collected during 48 h. On day 9, L-tryptophan was force-fed and the urine was collected during 48 h. Niacin metabolites such as N-methylnicotinamide (MNA), N-methyl-2 pyridone-5-carboxamide (2-Py) and N-methyl-4-pyridone-3-carboxamide (4-Py) in the urine samples were analyzed by chromatography. The activity of ACMSD in the liver and kidney was assayed immediately after the last urine collection. The results indicate that the urinary excretion of the niacin metabolites in the 40% Cas group was lower than that of the 20% Cas group in spite of the more intake of tryptophan in the former group. On the other hand, in the 40% Cas+ 20% F group, tryptophan intake was lower and the excretion of the metabolites was significantly higher than that in the 40% Cas group. The hepatic ACMSD activity in the 40% Cas group was 5.8 times that of the 20% Cas group and that in the 40% Cas + 20% F group was one tenth that of the 20% Cas group. These results indicate that the ratio of the excreted metabolites to the tryptophan intake was reduced by the high dietary protein level, but increased by the addition of high soybean oil. The data analysis shows that the amount of urinary total niacin metabolites ([TNM]: MNA + 2-Py + 4-Py) could be expressed in the following equation in the rats fed on each diet: [TNM] = 0.090 ([Trp] -22.5.delta w) [1/(1 + 2.4 [ACMSD])], where [ACMSD] is the hepatic ACMSD activity, [Trp] the tryptophan intake, and delta w the body weight gain. PMID- 1880631 TI - The effect of milk and skim milk intake on serum lipids and apoproteins in young females. AB - The effect of milk and skim milk intake on serum lipid and apoprotein levels was investigated in young females with consideration of each subject's menstrual period. When milk and dairy products were not allowed, the serum cholesterol concentration tended to decrease in high density lipoprotein (HDL) and very low density lipoprotein (VLDL), the triglyceride concentration tended to increase in HDL and low density lipoprotein (LDL), the phospholipid concentration showed no change, and the apoB, apoC-III and apoE significantly decreased. In the milk group, VLDL cholesterol and phospholipid concentrations were increased with a significant increase in the apoB concentration after intake of 200 ml/day of milk for one menstrual period, and these levels did not change when the milk intake was doubled. VLDL phospholipid increased and apoE decreased after the intake of 20 g/day of skim milk, and LDL cholesterol and HDL phospholipid concentrations tended to decrease when the skim milk intake was doubled. PMID- 1880632 TI - Ascorbic acid deficiency elevates serum level of LDL-cholesterol in a rat mutant unable to synthesize ascorbic acid. AB - The effect of ascorbic acid deficiency on serum levels of high density lipoprotein- (HDL-), low density lipoprotein- (LDL-), very low density lipoprotein- (VLDL-) and chylomicron-cholesterol was examined in ODS-od/od rat (ODS rat), that is a rat mutant unable to synthesize ascorbic acid. Male ODS rats were fed an ascrobic acid-free diet for 20 days. In another two groups, the diet supplemented with 300 mg ascorbic acid/kg diet was fed either ad libitum (ad libitum control) or in pair-feeding (pair-fed control). Pair-fed rats received the same amount of diet as rats fed the ascorbic acid-free diet. Serum level of total cholesterol in the ad libitum control rats, ascorbic acid-deficient rats, and the pair-fed control rats were 100.1 +/- 8.4 mg/dl, 92.8 +/- 6.2 mg/dl and 72.2 +/- 4.8 mg/dl, respectively. The level of LDL-cholesterol in ascorbic acid deficient rats was significantly higher than that in the ad libitum control or that in the pair-fed control. The level of HDL-cholesterol in ascorbic acid deficient rats was lower than that in the ad libitum control, but was not changed as compared with that in the pair-fed control. Ascorbic acid deficiency did not affect serum level of VLDL-cholesterol or chylomicron-cholesterol as compared with those in the controls. These results demonstrate that ascorbic acid deficiency causes the elevation of serum level of LDL-cholesterol both in ad libitum feeding condition and pair feeding condition. PMID- 1880633 TI - Effects of dietary pantethine levels on contents of fatty acids and thiobarbituric acid reactive substances in the liver of rats orally administered varying amounts of autoxidized linoleate. AB - The effects of dietary pantethine levels on the contents and compositions of fatty acids and on the levels of lipid peroxides were investigated with rat liver and its S-9 fraction under administration of 0 (non), 0.2 (low dose), and 0.35 ml (high dose) of autoxidized linoleate (AL) per 100 g body weight of the rats per day for 5 days. AL having 800 meq/kg of peroxide value (PV) and 1,700 meq/kg of carbonyl value (CV) was dosed to the rats of each group given drinking water containing 0 mg% (deficient), 6.25 mg% (adequate), and 125 mg% pantethine (excess). In the pantethine-deficient and -adequate groups, the contents of fatty acids both in the liver homogenate and in the S-9 fraction were correspondingly decreased by increasing dose levels of AL, and the decrease was remarkable especially in the pantethine-deficient group, but was not significant in the pantethine-excess group even by a high dose of AL. Particularly, in the high dose of AL, the notable decreases of oleic acid (C18:1) contents in both the liver and the S-9 fraction were observed in rats of the pantethine-deficient and -adequate groups. The thiobarbituric acid (TBA) values in the liver homogenate and the S-9 fraction were increased correspondingly by increasing dose levels of AL, and the increases were repressed in the pantethine-excess group. PMID- 1880634 TI - Effect of vitamin B2 deficiency on rat liver dihydropyrimidine dehydrogenase activity. AB - Effect of vitamin B2 deficiency on rat liver dihydropyrimidine dehydrogenase was investigated. It was found that the purified enzyme contains 2 mol flavin per molecule, which consists of equal proportions of flavin-adenine dinucleotide (FAD) and riboflavin 5'-phosphate (FMN). When rats were fed on a vitamin B2 deficient diet for 5 weeks, dihydropyrimidine dehydrogenase activity in the liver was diminished, followed by a decrease in enzyme concentration. Moreover, the addition of exogenous FAD or FMN did not restore the activity. Thus endogenous flavin may regulate the enzyme half-life or synthesis. Lowering of dihydropyrimidine dehydrogenase activity in the livers of rats fed on a vitamin B2-deficient diet did not affect the uridine, uracil and sigma UMP (the sum of acid soluble uracil 5'-nucleotides) pool in liver. PMID- 1880635 TI - Kidney injury induced by lipid peroxide produced by vitamin E deficiency and GSH depletion in rats. AB - Four-week-old Wistar male rats were fed a vitamin E (VE)-deficient (0E) or a VE sufficient (10E) diet for 6 weeks and then intraperitoneally treated with buthionine sulfoximine (BSO) at 1 mmol/kg body weight once a day for 3 days. Glutathione (GSH) depletion by BSO treatment caused injuries especially in the kidneys of VE-deficient rats. The kidney weight increased in the VE-deficient rats after BSO treatment (0E-BSO). It was observed that the epithelial cells of the renal tubules in this group were strongly impaired and the injuries were necrosis and desquamation. No injury was observed in the kidneys of the BSO untreated 0E group and the 10E groups. The TBA value of the kidney of 0E-BSO group was lower than that of the BSO-untreated 0E group, but the lipofuscin content of the kidney of the 0E-BSO group was 10 times higher than that of the BSO-untreated 0E group. These results suggest that the kidney injuries in rats may be caused by lipid peroxidation induced by vitamin E deficiency and glutathione depletion. PMID- 1880636 TI - [Immunohistological study of the nasal mucosa in allergic rhinitis with reference to B cell, T cell subpopulation, activated T cell and Langerhans cell]. AB - Distribution of B lymphocytes, T lymphocytes subpopulations, activated T lymphocytes and Langerhans cells of the nasal mucosa in 28 patients with nasal allergy ranging in age from 19 years to 54 years was studied. The specimens from inferior turbinates were frozen at -70 degrees C and sliced at a thickness of 4 microns by cryostat. Monoclonal antibodies and peroxidase-antiperoxidase staining (Ortho) were used to detect these cells. OKT4, OKT8, OKT6 and OKB19 were used as markers of helper/inducer T cells, suppresser/cytotoxic T cells, Langerhans cells and B cells, respectively. OKDR was used as a marker of activated T cells, B cells, Langerhans cells and macrophages. Many OKT4 and OKT8 positive cells were observed in lamina propria. In every case, more OKT4 positive cells were detected in number than OKT8 positive cells. Some OKB19 positive cells and macrophages were observed in lamina propria, but OKT6 positive cells were not observed. OKDR positive cells were observed in high density, and more OKDR positive cells were detected than OKT4, OKT8 and OKB19 positive cells. Most of the OKDR positive cells were small in size and round in shape. From these results, many T lymphocytes were thought to be activated, and T lymphocytes were thought to play an important role in nasal allergy. PMID- 1880637 TI - [Follow-up study of secretory otitis media after adenoidectomy and tonsillectomy]. AB - Questionnaires concerning the pre- and post- operative conditions were conducted on 92 patients with secretory otitis media who underwent adenotomy or adeno tonsillectomy. Fifty-three patients of them further received microscopic inspection of the eardrum and hearing tests. The questionnaires indicated that episodes of fever-up or cold decreased markedly after the operations. However, even after the operations, one-third of the patients experienced acute otitis media, and one-fourth complained of nasal symptoms such as nasal obstruction and nasal discharge. About a half of the patients showed normal findings of the eardrum after the operations. Secretory otitis media was cured in almost all cases; 80% of the ears showed type A tympanograms. However, about 35% of the ears showed unfavorable prognoses after the operations; recurrence and elongated cure were found in 75% and 25% of these ears, respectively. The younger the patients, the higher the incidence of unfavorable prognosis became. Recurrence was most frequently observed in patients younger than 6-year-old, and it usually occurred 4-9 months after the operations mainly in winter. The present study suggested that patients must be followed for at least 1 year after operation and that nasal symptoms must be carefully treated in patients not older than 5 years. PMID- 1880638 TI - [A study on auditory disturbances after microvascular decompression for hemifacial spasm]. AB - After establishing an operation of microvascular decompression by Jannetta in 1975, an improvement rate of hemifacial spasm have increased. However, postoperative hearing deficits, equilibrium disturbances and facial paresis have been described in some publications. Fifty-seven of 119 patients with hemifacial spasm operated from 1982 to 1989, were examined by audiometry before and after operation. In patients with tinnitus at the time of facial spasm and closing eyelids, tinnitus improved almost in many cases. Of 57 patients, 8 (5 with sensorineural hearing loss, 3 with conductive hearing loss) had postoperative hearing impairments in operated ears, and 7 (7 with sensorineural hearing loss) had in the other ears, too. Of 7 patients having sensorineural hearing loss observed for several months, 4 having slight sensorineural hearing loss recovered at the same hearing level before operation. In 2 patients having profound sensorineural hearing loss, however, hearing improvement did not observed in each case. PMID- 1880639 TI - [Familial deafness showing hearing pattern of low-tone losses]. AB - Clinical and electrocochleographic studies of low tone familial deafness were carried out in 19 patients of 10 families. These hearing impairments were characterized by an upward-sloping pure tone audiogram with 50dB to 60dB hearing threshold below 2000Hz and with normal or near-normal hearing threshold above this frequency. The type of inheritance in these families showed autosomal dominant mode and no associated malformation. In 7 patients, hearing tests were repeated, it was observed that hearing threshold was not elevated. The short increment sensitivity index (SISI) tests were positive suggesting a hair cell lesion in tested 7 patients. The caloric tests were normal in tested 3 patients. No abnormal internal ear configuration was found in both X-ray and high resolution computed tomography. Twelve patients with these familial low tone deafness (FLTD), 19 patients with Meniere's disease, and 9 patients with low tone sudden deafness (LTSD) were studied using the transtympanic electrode technique of electrocochleography. All patients of FLTD showed normal negative summating potential (-SP) amplitude, and the cochlear microphonics (CM) showed a nearly same detection threshold as hearing level of the pure tone audiogram at 1 kHz and 0.5 kHz. The evidence suggested that the hearing impairment resulted from a localized abnormality of the cochlear apex, and without endolymphatic hydrops. On the other hand, patients with Meniere's disease and LTSD showed a high -SP amplitude and a satisfactory detection threshold of CM compared with hearing level of the pure tone audiogram. These findings suggest that both Meniere's disease and LTSD relate to endolymphatic hydrops. PMID- 1880640 TI - [Epidemiological analysis of otitis media with effusion in children]. AB - A study was conducted on 153 children with otitis media with effusion to assess risk factors for otitis media with effusion. Information was collected by questionnaire survey, clinical examination and audiological tests including tympanography. We investigated two groups of children with otitis media with effusion. Group 1 consisted of 70 children with otitis media with effusion who had not undergone myringotomy. Group 2 consisted of 83 children with otitis media with effusion who had undergone myringotomy. Bottle feeding and adenoidal hypertrophy occurred more frequently in Group 2 than in Group 1. These observations provide an epidemiologic and clinical basis for further investigations of otitis media with effusion. PMID- 1880642 TI - [Morphological study of cochlea in experimental chronic serum sickness]. AB - Relationship of circulating immune complexes to some inner ear disorders has been suggested recently. Thus, bovine serum albumin (BSA) nephritis, a model of chronic serum sickness, was made and morphological, immunological studies of cochlea were performed using light microscopy, transmission electron microscopy and immunofluorescent antibody methods. Group 1 consisted of animal sensitized with daily BSA injections for 90 days; in group 2, BSA was administered for 70 days, daily, and after a three-weeks interval, injections were continued for another 21 days; group 3 consisted of animals sensitized with daily BSA injections for 100 days followed by BSA injection into the facial nerve via the stylo-mastoid foramen. The animals (group 3) were sacrificed on day 1 and 4 following facial nerve sensitization for examination of cochlear morphological changes. No morphological changes were observed (group 1). Protrusion of marginal cells into endolymphatic space was seen, because of swelling of endoplasmic reticulum of the cells of stria vascularis's (group 2). Slight hydrops was present mainly in the basal turn (group 3). No IgG deposits were found in all groups. It appears that the changes in group 2 were caused by rather chronic nephritis than immune reaction. We conclude that damage induced in the cochlea is negligible compared to the extensive lesions observed in the kidney in chronic serum sickness. PMID- 1880641 TI - [Parapharyngeal space lesions: with a reference to biopsy]. AB - We received seven cases of parapharyngeal space lesions and discussed on necessity of biopsy. Tumors originating in the parapharyngeal space were represented by parotid pleomorphic adenomas which showed bulging of soft palate and tonsillar fossa, and benign neurogenic tumors which showed bulging of the lateral wall of the meso-pharynx. In these cases, preoperative biopsy was not necessary unless the lesion was suspected, of malignancy by CT, MRI and so on. In the case of bulging of soft palate and tonsillar fossa, if CT or MRI finding shows that the tumor is localized in the median portion of the parapharyngeal space and is separated from greater vessels and nerves existing in the parapharyngeal space, therapeutic protocol might be planned after an establishment of histological diagnosis with biopsy. In the case of a bulging lateral wall of the meso-pharynx with a history of malignant neoplasm of the head and neck, lymph node metastasis should be thought about. PMID- 1880643 TI - [Use of a butterfly ventilation tube in the treatment of otitis media with effusion]. AB - Sixty-three ears of 49 patients with serous otitis media were treated making use of butterfly ventilation tube in our 4 hospitals and 1 private office. The average time from intubation to extubation was 9 months and the longest case was 33 months. Main complications were infection and spontaneous extubation. The rate of hearing improvement after tympanostomy was more than 80% in all cases. The frequency of the most improvement was observed in 1kHz on the average. It was cleared that the butterfly ventilation tube was easy to use for the wide age patients and at any clinics. It was concluded that the butterfly ventilation tube was useful as a long-term ventilation tube. PMID- 1880644 TI - [Visual scoring in the auditory brainstem response. Second report: determination of response threshold]. AB - In the ABR audiometry we usually determine the threshold by visual scoring. The evaluation of visual scoring has been investigated in my laboratory for several years, using the traced samples of ABR obtained from 3 normal adults same as that described in my previous report. Stimuli were clicks of 0, 5, 10, 15, 20, 30dBSL and without stimulus. Thresholds were calculated by the two psychophysical methods, "method of limits" and "up and down method". Scorers were two groups: 3 experienced and 3 inexperienced. Results obtained were as follows: 1. In the method of limits, averages of thresholds measured by the experienced scorers were contained 6.0-9.8dB, their standard deviations being 3.82-6.40dB. 84-95% of all thresholds were contained 0-10dB or 5-10dB in the experienced group. 2. In the method of limits, the highest rate that all scorers of a group had the same threshold was 56% in the separate presentation in the experienced group. 3. In the up and down method averages of threshold were contained 4.6-9.1dB, which were smaller than the method of limits, and standard deviations were contained 1.77 3.18dB, which were about 1/2 times in the method of limits. 92-99% of all thresholds were contained 0-5dB or 5-10dB. PMID- 1880645 TI - Neutrophil function disorders: pathophysiology, prevention, and therapy. PMID- 1880646 TI - Reference data on gains in weight and length during the first two years of life. AB - Serial data from studies of infants at the University of Iowa and from the Fels Longitudinal Study were used to develop sex-specific percentiles for increments in weight and recumbent length for selected intervals during the first 24 months of life. Weight increments are presented for 1-month intervals from birth to 6 months, 2-month intervals from birth to 12 months, and 3-month intervals from birth to 24 months. Length increments are presented for 2-month intervals from birth to 6 months, and for 3-month intervals from birth to 24 months of age. Weights and lengths at the target ages were obtained for the Iowa data by simple interpolation, and for the Fels data by fitting families of three-parameter mathematical functions to the serial data from ages 1 to 24 months. The tabular presentations are based on the Iowa data from birth to 3 months of age, on the combined Iowa and Fels data from 3 to 6 months of age, and on the Fels data from 6 to 24 months of age. We believe that these reference data will be useful in screening for deviations from normal growth and may aid in early detection of failure to thrive or excessive weight gain during early life. PMID- 1880647 TI - Relevance of common tests of cerebrospinal fluid in screening for bacterial meningitis. AB - This study tests the hypothesis that if cerebrospinal fluid (CSF) has a nucleated blood cell count (NucBC) of less than 6/mm3, CSF tests other than bacterial culture need not be performed to exclude the diagnosis of bacterial meningitis in patients not receiving antimicrobial agents. The results of tests performed on the first specimen of CSF obtained for a given hospital visit from children younger than 3 years of age, exclusive of newborn infants admitted to the hospital on their date of birth, were analyzed. Of 3356 CSF specimens evaluated, 122 were from patients with bacterial meningitis; 460 specimens were analyzed separately because the erythrocyte count was greater than 1000/mm3. A negative CSF screening test result was defined as a CSF NucBC less than 6/mm3. In facilitating the diagnosis of bacterial meningitis, this screening test had a sensitivity of 98.4%, a specificity of 75.2%, and a negative predictive value of 99.9%. The other CSF tests varied widely in screening effectiveness: a Gram stained smear had a sensitivity of 53% and a specificity of 97%. Receiver operating characteristic curve analysis was used to assess the screening relevance of CSF tests. The CSF NucBC and CSF segmented NucBC performed indistinguishably and superiorly compared with the CSF protein or glucose concentration and the ratio of CSF glucose to serum glucose concentration. Logistic regression analysis showed that the NucBC alone is superior to any combination of the other CSF tests. In a prospective study of 215 children younger than 3 years of age undergoing a lumbar puncture in our emergency department, 85% had empiric criteria identifying them as appropriate for an abbreviated CSF evaluation. The CSF NucBC was less than 6/mm3 in 70% of the 181 patients who would have been eligible for an abbreviated CSF evaluation. These data suggest that a strategy for the sequential testing of CSF could be adopted that would exclude unnecessary determinations and thereby save time, effort, and health care dollars. PMID- 1880648 TI - Value of degenerative change in neutrophils as a diagnostic test for Kawasaki syndrome. AB - STUDY OBJECTIVE: To determine whether the presence of vacuoles and toxic granulation in neutrophils can be used as a diagnostic test to help differentiate children with Kawasaki syndrome from those with clinically similar illnesses. DESIGN: Peripheral blood smears of 23 patients with Kawasaki syndrome, 23 disease control patients, and 23 hematology laboratory control subjects were examined in random order by technicians unaware of either the diagnosis or the previously recorded laboratory results. SETTING: Tertiary care children's hospital in Ottawa, Canada. PATIENTS: All 23 consecutive patients with Kawasaki syndrome satisfied established criteria for the diagnosis. Disease control patients were selected from the hospital registry of patients with other illnesses frequently considered as part of the differential diagnosis for Kawasaki syndrome. MEASUREMENTS AND MAIN RESULTS: Compared with disease control patients, patients with Kawasaki syndrome had a higher percentage of neutrophils with vacuoles (mean +/- SEM, 31% +/- 5% vs 14% +/- 3%; p = 0.006) and toxic granulation (mean +/- SEM, 43% +/- 7% vs 14% +/- 4%; p less than 0.001). If the sum of the number of neutrophils with vacuoles and the number with toxic granulation (per 100 mature neutrophils examined) was at least 70, this "toxic neutrophil" test had a specificity of 0.96 and a likelihood ratio of a positive test result of 12. CONCLUSIONS: Degenerative change in neutrophils is common in the early stages of Kawasaki syndrome. The toxic neutrophil test is potentially a helpful adjunct to the clinical examination, particularly in the case of infants and other patients with subtle manifestations who might otherwise be at risk for delayed diagnosis. PMID- 1880649 TI - Asymptomatic constant isolated proteinuria in children. AB - The clinical features, renal biopsy findings, and subsequent course in 53 children with asymptomatic constant isolated proteinuria were studied retrospectively (1) to determine the prevalence of renal pathologic abnormalities among these children, (2) to identify those clinical characteristics that may enable recognition of children with an increased likelihood of having renal pathologic abnormalities, and (3) to assess the clinical course. All biopsy specimens were examined by light, immunofluorescence, and electron microscopy. Twenty-five patients (47%) had significant glomerular changes (15 had focal segmental glomerulosclerosis, 4 IgA nephropathy, 3 diffuse mesangial proliferative glomerulonephritis without IgA deposition, and 3 membranous glomerulonephritis), and 28 had minimal glomerular changes. There were no differences between the patients with significant glomerular changes and those with minimal glomerular changes with regard to clinical and laboratory findings except for a predominance of boys in the former group. At the latest follow-up, seven patients with significant glomerular changes, but none with minimal glomerular changes, had chronic renal impairment. Because of the high incidence of significant glomerular changes and the high rate of progression to chronic renal impairment, we believe that a renal biopsy is indicated for a child with asymptomatic constant isolated proteinuria. PMID- 1880650 TI - High incidence of serum antibodies to Escherichia coli O157 lipopolysaccharide in children with hemolytic-uremic syndrome. AB - Because the classic hemolytic-uremic syndrome has been etiologically linked to intestinal infections by Escherichia coli O157 and other verotoxin-producing E. coli (VTEC), we examined 22 consecutive children with acute hemolytic-uremic syndrome for the presence of VTEC, using microbiologic methods, and for a specific immune response to O157 lipopolysaccharide in acute-phase and follow-up sera, using the indirect hemagglutination assay and the immunoblot procedure. Of 22 children with enteropathic hemolytic-uremic syndrome, 15 (68%) had evidence of VTEC infection by culture of the pathogen or detection of free verotoxin in the feces, or both. Significantly elevated titers of short-lived agglutinins and IgM class antibodies against the O157 lipopolysaccharide were found in 20 (91%) of 22 patients, but not in two of three patients with non-O157 E. coli isolates or in healthy children or children with diarrhea caused by other enteric pathogens (p less than 0.01). The combined microbiologic and serologic procedures provided evidence for VTEC infection in all 22 patients. The high incidence of anti-O157 lipopolysaccharide antibodies in these patients indicates the predominance and the pathogenic potential of this serogroup. Both serologic techniques proved to be valuable tools to further characterize this form of hemolytic-uremic syndrome. Future studies on the induction of protective immunity seem warranted. PMID- 1880651 TI - Natural history of isolated atrial flutter in infancy. AB - To clarify the natural history of isolated (i.e., without associated congenital cardiac anomalies) atrial flutter in infancy, we reviewed the clinical course in nine patients who were seen with this arrhythmia in the first year of life (range 1 day to 4 months). Atrial flutter was identified by the typical sawtooth pattern in leads II, III, and aVF of the surface electrocardiogram or the pattern of atrial flutter on an atrial electrogram recorded through the esophagus. The mean cycle length of the atrial flutter was 151 msec (atrial rate 397 beats/min). Six of the nine patients had other perinatal problems, such as immune and nonimmune hydrops fetalis (two patients), pneumonia (one patient), anemia (five patients), or low birth weight (one patient). In all patients the rhythm reverted to normal, either spontaneously (two patients), with overdrive pacing (four patients), or after oral digoxin therapy (three patients). No consistent temporal relationship between digoxin administration and conversion was observed; conversion was instantaneous in the four patients who received atrial overdrive pacing. Four patients were discharged receiving digoxin therapy (6 months to 1 year). One patient had supraventricular tachycardia after discharge that was controlled with digoxin. No recurrence of atrial flutter was observed among the nine patients during a mean follow-up of 6.8 years (range 0.2 to 20 years). We conclude that isolated atrial flutter in infancy is rare, has a good prognosis, may be related to transient perinatal events, and often spontaneously converts to normal sinus rhythm; however, when it does not, it will respond to transesophageal pacing. Acute and chronic digoxin therapy is probably unnecessary. PMID- 1880652 TI - Molecular analysis of X-linked agammaglobulinemia with growth hormone deficiency. AB - To address the relationship between the gene (or genes) that causes the syndrome of X-linked hypogammaglobulinemia with isolated growth hormone deficiency and the gene responsible for typical X-linked agammaglobulinemia (XLA), we have used cytogenetics, examination of X chromosome inactivation patterns in potential carriers of the defect, and linkage analysis to study two unrelated families in which the affected males had isolated growth hormone deficiency and immunologic findings indistinguishable from those of typical XLA. A deletion could not be demonstrated in either family by G-banded karyotypes or flow cytometric analysis of metaphase chromosomes. Studies of X inactivation showed that mothers of affected boys from both families exhibited selective use of a single X chromosome as the active X chromosome in B cells but not T cells. This pattern is the same as that seen in obligate carriers of typical XLA. Linkage analysis demonstrated the most likely location for this gene (or genes) to be the midportion of the long arm of the X chromosome between DXS3 and DXS94. This segment of the X chromosome, which constitutes approximately 5% of the total X chromosome, encompasses the gene for XLA. These findings are consistent with the combination of XLA and growth hormone deficiency being caused by a small, contiguous, gene deletion syndrome involving the gene for XLA or an allelic variant of the gene for typical XLA. PMID- 1880653 TI - Hyperlipidemia and fatty acid composition in patients treated for type IA glycogen storage disease. AB - Because glycogen storage disease type IA (GSD-IA) is characterized by recurrent episodes of hypoglycemia that promote a marked elevation in blood triglyceride levels, we evaluated plasma lipid levels in 12 patients with GSD-IA on a regular basis. Six of the 12 patients had plasma fatty acid composition measured; because of possible essential fatty acid deficiency, urinary prostaglandin excretion was also measured. All patients had triglyceride levels between 1440 and 6120 mg/dl (16.25 to 69.09 mmol/L) before treatment. After treatment to promote blood glucose levels of 75 to 85 mg/dl (4.2 to 4.7 mmol/L), triglyceride levels in each of 11 patients were between 189 +/- 31 (2.13 +/- 0.35 mmol/L) and 510 +/- 60 mg/dl (5.76 +/- 0.68 mmol/L). The lipoprotein fatty acid composition in six patients showed a substantial elevation in C16:0, C16:1 omega 7, and C18:1 omega 9, but no increase in C20:3 omega 9 (the fatty acid that characteristically increases in essential fatty acid deficiency). In addition, each of the six patients had normal 24-hour urinary excretion of prostaglandin. One patient, whose triglyceride levels remained elevated despite dietary treatment, was given either clofibrate, lovastatin, niacin, or fish oil. With the exception of lovastatin, these agents produced a decrease in triglyceride values for 1 to 2 months; however, by 3 months triglycerides reached pretreatment levels. Combined treatment with clofibrate and niacin resulted in a sustained decrease in plasma triglyceride levels for 4 months. The findings indicate that dietary management of GSD-IA is usually associated with improvements in triglyceride levels; however, patients maintain triglyceride values between 300 and 500 mg/dl (3.38 to 5.65 mmol/L). No patient had biochemical evidence of essential fatty acid deficiency. PMID- 1880654 TI - Juvenile hyaline fibromatosis: a report of two severe cases. AB - Two unrelated children with a severe form of juvenile hyaline fibromatosis are described. In addition to painful flexion contractures of all of the large joints, oral and skin lesions, and typical radiologic appearance of osteolytic defects, both girls had marked growth retardation and recurrent infections. Both children died in early infancy of overwhelming infection. PMID- 1880655 TI - Effect of diphtheria-tetanus-pertussis immunization on prolonged apnea or bradycardia in siblings of sudden infant death syndrome victims. AB - To determine whether the incidence of apnea or bradycardia increased after the first diphtheria-tetanus-pertussis (DTP) immunization in 100 subsequent siblings of victims of sudden infant death syndrome, we examined data obtained from floppy disk recordings attached to apnea-bradycardia monitors for episodes of apnea lasting 15 seconds or longer and episodes of bradycardia lasting 10 seconds or longer. The data were divided into three periods: (1) 10 days before the first DTP immunization was received (pre-DTP period), (2) 10 days immediately after the DTP (DTP period), and (3) 10 days after the DTP period (post-DTP period). Seventeen infants had at least one episode of prolonged apnea or prolonged bradycardia either before or after the 30-day study period (eight before only, eight after only, and one before and after). None of the infants had episodes of apnea lasting 15 seconds or more or bradycardia lasting 10 seconds or more during the pre-DTP or DTP period. One episode of apnea, 16 seconds long, and one episode of bradycardia lasting 11 seconds occurred in the post-DTP period. These results failed to confirm the clinical impression that DTP immunizations are associated with an increased frequency and severity of prolonged apnea. They also place in question the utility of assessing an infant's response to a DTP immunization to determine continued risk of apnea and bradycardia before home monitoring is discontinued. PMID- 1880656 TI - Reference data for assessing growth of infants. PMID- 1880657 TI - New Ballard Score, expanded to include extremely premature infants. AB - The Ballard Maturational Score was refined and expanded to achieve greater accuracy and to include extremely premature neonates. To test validity, accuracy, interrater reliability, and optimal postnatal age at examination, the resulting New Ballard Score (NBS) was assessed for 578 newly born infants and the results were analyzed. Gestational ages ranged from 20 to 44 weeks and postnatal ages at examination ranged from birth to 96 hours. In 530 infants, gestational age by last menstrual period was confirmed by agreement within 2 weeks with gestational age by prenatal ultrasonography (C-GLMP). For these infants, correlation between gestational age by NBS and C-GLMP was 0.97. Mean differences between gestational age by NBS and C-GLMP were 0.32 +/- 1.58 weeks and 0.15 +/- 1.46 weeks among the extremely premature infants (less than 26 weeks) and among the total population, respectively. Correlations between the individual criteria and C-GLMP ranged from 0.72 to 0.82. Interrater reliability of NBS, as determined by correlation between raters who rated the same subgroup of infants, ws 0.95. For infants less than 26 weeks of gestational age, the greatest validity (97% within 2 weeks of C-GLMP) was seen when the examination was performed before 12 hours of postnatal age. For infants at least 26 weeks of gestational age, percentages of agreement with C GLMP remained constant, averaging 92% for all postnatal age categories up to 96 hours. The NBS is a valid and accurate gestational assessment tool for extremely premature infants and remains valid for the entire newborn infant population. PMID- 1880658 TI - Immediate improvement in lung volume after exogenous surfactant: alveolar recruitment versus increased distention. AB - To determine whether changes in lung volume may be responsible for the clinical improvement in preterm infants given exogenous surfactant, we measured functional residual capacity (FRC), lung mechanics, and partial pressure of oxygen in seven ventilated neonates (birth weight 1080 +/- 361 gm (mean +/- SD); gestational age 28.3 +/- 2.6 weeks) less than 9 hours of age who had findings typical of hyaline membrane disease. All patients received 100 mg/kg calf lung surfactant extract. FRC was measured by a closed-circuit helium-dilution technique, and lung mechanics were determined by least mean squares analysis. FRC increased in all patients (range 56% to 330%; p less than 0.03). Dynamic lung compliance and total airway conductance did not change. Mean +/- SEM specific lung compliance (dynamic lung compliance/FRC) decreased 55.93% +/- 4.27% (p less than 0.02) and mean specific conductance (total airway conductance/FRC) decreased 45.91% +/- 9.74% (p less than 0.009). Mean alveolar/arterial partial pressure of oxygen ratio decreased 51.0% +/- 8.67% (p less than 0.01). These data indicate that the immediate improvement in oxygenation after surfactant administration is related to increased lung volumes. The decrease in specific lung compliance and specific airway conductance is suggestive of increased distention rather than recruitment of functional alveoli. PMID- 1880659 TI - Tactile-kinesthetic stimulation effects on sympathetic and adrenocortical function in preterm infants. AB - The purpose of our study was to investigate the neuroendocrine response in preterm infants to a pattern of tactile-kinesthetic stimulation that facilitates their growth and development. Preterm infants (mean gestational age 30 weeks, mean birth weight 1176 gm) received normal nursery care or tactile-kinesthetic stimulation for three 15-minute periods at the start of three consecutive hours each day for 10 days. On day 1 and day 10 of the study, a 24-hour urine sample was collected for norepinephrine, epinephrine, dopamine, cortisol, and creatinine assay and a blood sample was taken by heel stick for cortisol and growth hormone assay. Urine norepinephrine and epinephrine values increased significantly only in the stimulated babies. Urine dopamine and cortisol values increased in both groups, and serum growth hormone decreased in both groups. Individual differences in urine norepinephrine, epinephrine, dopamine, and cortisol values were highly stable across the 10 days despite a 10-fold range of values among the infants. The results of this study suggest that tactile-kinesthetic stimulation of preterm infants has fairly specific effects on maturation and/or activity of the sympathetic nervous system. In addition, this study has defined catecholamine and cortisol secretion across gestational age in normal preterm infants. Finally, these data suggest that highly stable individual levels of catecholamine and cortisol secretion are established by birth in humans. PMID- 1880660 TI - Changes in left ventricular output from fetal to early neonatal life. AB - Using pulsed Doppler and two-dimensionally directed M-mode echocardiographic techniques, we measured left ventricular (LV) output, stroke volume, heart rate, LV end-diastolic dimension (LVEDD), LV end-systolic dimension, and LV percent fractional shortening (%FS) in 34 normal term infants 12 to 24 hours before parturition and thereafter serially 1, 24, and 96 hours after birth. Stroke volume was calculated as the product of the aortic flow velocity integral and aortic valve area. There was a twofold increase in LV output 1 hour after birth (fetal 170 +/- 46 ml/min/kg vs 1 hour 327 +/- 66 ml/min/kg; p less than 0.01) which was associated with significant increases in stroke volume, %FS, and LVEDD (stroke volume 1.21 +/- 0.33 ml/kg vs 2.25 +/- 0.37 ml/kg; %FS 34.3% +/- 5.8% vs 37.7% +/- 5.4%; LVEDD 15.4 +/- 1.1 mm vs 17.7 +/- 1.4 mm). Heart rate did not change 1 hour after birth. During the subsequent hours after birth, LV output decreased significantly to a value of 245 +/- 56 ml/min/kg (p less than 0.01) at 24 hours, which did not change 96 hours after birth. There were significant declines in stroke volume, LVEDD, and heart rate 24 hours after birth (stroke volume 2.02 +/- 0.42 ml/kg; LVEDD 17.0 +/- 1.1 mm; heart rate 121 +/- 11 beats/min). The %FS remained unchanged within the first 96 hours of age. These results indicate that the major regulator of LV output immediately after birth is stroke volume and not heart rate. The increase in stroke volume is related to an increase in LV size and LV myocardial contractility. Our data provide a useful basis for the interpretation of abnormal LV function in the early neonatal period. PMID- 1880661 TI - Effects of surfactant therapy on outcome of infants with birth weights of 600 to 750 grams. PMID- 1880662 TI - Group B streptococcal latex agglutination testing in neonates. PMID- 1880663 TI - Comparison of oral and parenteral vitamin K prophylaxis for prevention of late hemorrhagic disease of the newborn. PMID- 1880664 TI - Effect of high altitude on neutrophil counts in newborn infants. PMID- 1880665 TI - Pharmacokinetic and pharmacodynamic study of midazolam in children during esophagogastroduodenoscopy. AB - We undertook a prospective study to evaluate the relationship between the onset and degree of sedation and the midazolam plasma concentration in children between 6 and 18 years of age during esophagogastroduodenoscopy. Thirteen boys and seven girls (median age 13.5 years) were studied. Midazolam was injected intravenously for 5 minutes, and the dose was titrated to sedation or a maximum dose of 0.1 mg/kg was given. Plasma midazolam concentration was determined just before and at 5, 10, 15, 30, 45, and 60 minutes after the start of midazolam injection. The patient's level of sedation was evaluated by an assistant at each blood sampling time. Clearance, volume of distribution, and terminal elimination (beta) half life were estimated from a biexponential fit of the serial plasma midazolam concentrations. Mean beta half-life of midazolam was 47 +/- 26 minutes and mean clearance was 10.0 +/- 5.0 ml/min per kilogram of body weight. Maximum level of sedation occurred at 5 minutes after initiation of the injection and corresponded to a mean peak midazolam serum concentration of 229 +/- 39 micrograms/L. Thereafter, a decline of mean sedation scores paralleled the decrease in midazolam concentration. Mean oxygen saturation remained greater than 94% during the study. We conclude that children metabolize and excrete midazolam more rapidly than adults do and that sedation adequate for endoscopy is safely achieved in the majority of children with a midazolam dose of 0.05 to 0.1 mg/kg and a mean peak midazolam concentration greater than 200 microgram/L. PMID- 1880666 TI - Successful medical treatment of presumed Candida endocarditis in critically ill infants. AB - Few infants have been reported who survived fungal endocarditis; all have required both surgical and intensive antifungal therapy. We describe three infants, two weighing less than 1000 gm, who survived Candida endocarditis without surgery. Two had Candida parapsilosis, an agent not previously reported as a cause of neonatal endocarditis. All three infants were treated with amphotericin B and 5-flucytosine. Despite administration of 44, 38, and 48 mg/kg amphotericin B, respectively, no nephrotoxicity was noted; 5-flucytosine therapy was stopped in one infant because of thrombocytopenia. One infant died of an unrelated cause 6 months later; there was no evidence of Candida or endocarditis at autopsy. The other two infants are thriving 2 and 3 years after the completion of antifungal therapy; no remaining evidence of endocarditis is present on echocardiography. We conclude that antifungal therapy without surgery is an option for Candida endocarditis in critically ill infants. PMID- 1880667 TI - Effects of two different regimens of recombinant human growth hormone therapy on the bone mineral density of patients with growth hormone deficiency. PMID- 1880668 TI - Benefit of oral immune globulin therapy in patients with immunodeficiency and chronic diarrhea. PMID- 1880669 TI - Cutaneous lesions associated with cyclosporine therapy in pediatric renal transplant recipients. PMID- 1880670 TI - Treatment of cystinosis with cysteamine from early infancy. PMID- 1880671 TI - Antimicrobial treatment of acute otitis media. AB - No single antimicrobial drug is best suited for all patients with AOM. Amoxicillin and TMP-SMZ, however, remain first-line drugs in the initial treatment of uncomplicated AOM in the non-neonate. In other situations the drug selected depends on the patient's age, associated illnesses, recent history of otitis media, and drug hypersensitivity. Pharmacokinetic studies of AOM treatment are essential in generating more precise recommendations for antimicrobial drug use. PMID- 1880672 TI - Renal acidification during infantile diarrhea with acidosis. PMID- 1880673 TI - Dose dependency of time of onset of radiation-induced growth hormone deficiency. PMID- 1880674 TI - Blau syndrome versus sarcoidosis. PMID- 1880675 TI - Management of the febrile patient at risk of having bacteremia. PMID- 1880676 TI - Predicting the need for hospitalization of children with asthma. PMID- 1880677 TI - Ribavirin therapy for acute bronchiolitis: need for appropriate controls. PMID- 1880678 TI - The sub-specific numerical analysis of Candida albicans. AB - This paper reports the numerical analysis of 100 strains of Candida albicans using 96 physiochemical characters. Principal co-ordinate analysis and the modified multidimensional group analysis (MGA) method were used for the numerical analysis. MGA detected optimal solutions for five, 11, 15 and 17 groups. A single large swarm represented the majority of strains for the five- and 11-group solutions. Of the remaining two solutions only the 17-group solution was analysed further as the 15-group solution was close to the 17-group solution and contained less information. Of the 17 groups within the data, 10 "groups" contained only a single member, whilst the other groups contained 32, 24, 14, 13, three, two and two members each. Characters that tended to distinguish between the four larger groups included colonial fringe state, valerate assimilation, and resistance to borate, cetrimide, benzalkonium chloride, chlorhexidine, arsenate and salt. These larger groups appeared to form reasonably distinct clusters when tested by Sneath's overlap statistics. However, as the squared Euclidean distances between these group centroids were small, it would appear that most strains of C. albicans form a single swarm. It is suggested that these groups may represent "preferred phenotypes" for C. albicans, between which individual strains may switch. PMID- 1880680 TI - Sequence of the Candida albicans gene encoding the secretory aspartate proteinase. AB - The gene encoding the Candida albicans aspartate proteinase that is secreted by cells grown in protein-containing media was cloned from a C. albicans genomic bank. The base sequence of the insert shows a 1173 bp open-reading frame and indicates an amino acid sequence typical of aspartate proteinases, with amino acid sequence homology to other enzymes of this class and a putative signal peptide consisting of 50 amino acids upstream of the active enzyme. PMID- 1880679 TI - Deficient utilization of succinate in a sterol 14 alpha-demethylation mutant of Candida albicans. AB - Growth of a wild-type strain (KD14) started after a lag of approximately 15 h when glucose-grown cells of Candida albicans were incubated at 25 degrees C, with succinate as a sole energy/carbon source. No growth was observed, however, for a sterol 14 alpha-demethylation mutant (KD4900). During the lag period, the wild type cells retained their respiratory activity, as measured with glucose as an added substrate, and developed the capacity to incorporate labelled succinate. In contrast, incubation with succinate for 15 h resulted in diminished respiratory activity and failed to induce the succinate uptake capacity of the mutant cells. These two differences from the wild-type seem to account for the inability of the mutant to grow in the presence of a non-fermentable substrate. PMID- 1880681 TI - Biochemical and morphological effects of polyamine biosynthesis inhibitors on Trichophyton and Microsporum. AB - The minimum inhibitory concentrations (MICs) of three known irreversible inhibitors of polyamine synthesis, alpha-difluoromethylornithine (DFMO) and monofluoromethyldehydroornithine methylester (MFMOme), inhibitors of ornithine decarboxylase (ODC) and alpha-difluoromethylarginine (DFMA), an inhibitor of arginine decarboxylase (ADC), were determined for 10 species of dermatophytic fungi. Trichophyton species were generally more sensitive to these inhibitors than Microsporum species. Both genera produced arginase, and treatment of members of either genus with DFMO or DFMA resulted in an inhibition of ODC activity and a depletion of cellular polyamines. However, conversion of labelled DFMA to DFMO, either in vivo or in vitro, could not be demonstrated in spite of both genera producing arginase. The ultrastructure of cells cultured in the presence of either DFMO or DFMA was similar, and revealed disruption of calcium metabolism, an increase in mitochondrial number and alterations to membrane systems. DFMA and DFMO also inhibited sporulation in Microsporum gypseum. Our findings indicate that DFMO limits the growth of dermatophytes by direct inhibition of ODC and lowering of cellular polyamine levels; in contrast, DFMA inhibits polyamine synthesis in an unspecified manner as ADC activity was undetected. PMID- 1880682 TI - Immunolocalization of Aspergillus fumigatus mycelial antigens. AB - Specific immunoglobulin from the sera of patients with antibodies to Aspergillus and from antisera raised in rabbits to Aspergillus fumigatus fractions bound almost exclusively to the mycelial wall, as shown by immunogold labelling of ultra-thin sections. Different layers of the wall were labelled, depending on the source of the antigen used to produce antibody. Internal, cytoplasmic components were generally not labelled, except with antisera raised to crude wall material and to a Concanavalin A (ConA)-binding fraction of a water-soluble preparation. PMID- 1880683 TI - Mannan estimation as a measure of the growth of Candida albicans. AB - Determination of Candida albicans mannan levels by an enzyme-linked immunosorbent assay was compared with dry weight measurement and viable counting as a means to estimate growth of the fungus in broth cultures. Levels of extracted mannan showed good correlation with fungal biomass (dry weight) (r = 0.984) and, although biomass and mannan levels correlated with viable counts, the correlation was not as strong (r = 0.954-0.959). The technique offered an accurate alternative to viable counts in the brain and kidney when mannan estimation was used to follow the distribution of C. albicans in an experimental model of systemic candidosis in mice. Mannan levels were less useful in following the course of the infection in the liver and spleen where accumulation of free and serum-bound mannan was a problem. Mannan estimation would therefore seem to offer an accurate alternative to viable counts for determining the quantity of Candida both in vitro and in certain infected organs of experimental animals, where measurement of fungal biomass is not feasible and viable counts can be grossly inaccurate. PMID- 1880684 TI - Agar disk diffusion susceptibility tests with cilofungin (LY 121019). AB - Cilofungin (LY 121019) is a semi-biosynthetic lipopeptide agent which is active both in vitro and in vivo against isolates of Candida species. The purpose of this study was to demonstrate the usefulness of experimental 10- and 20 micrograms cilofungin disks in predicting probable in vitro susceptibility to this drug. Fifty-two isolates of pathogenic yeasts, which included 34 isolates of Candida albicans, 10 isolates of Candida tropicalis and eight isolates of Candida glabrata, were tested. Both agar dilution minimal inhibitory concentration (MIC) tests and matched agar disk diffusion tests were performed using 14-h-old broth cultures grown in single strength yeast nitrogen base (YNB) supplemented with asparagine and dextrose. Both tests were incubated at 35 degrees C and the results were read after 24 h. Regression analysis was used to measure the degree of correlation between MIC values and matched averaged zones of inhibition, and demonstrated that both the 10-micrograms (r = 0.9278) and 20-micrograms (r = 0.9082) disks can predict probable MIC values. PMID- 1880685 TI - Prevalence of Trichosporon beigelii. Colonization of normal perigenital skin. AB - Although the natural habitat of Trichosporon species is considered to be the soil, the role of normal skin in the carriage of Trichosporon beigelii is unknown. The purpose of this study was to determine the prevalence of T. beigelii colonization on normal perigenital skin. Inguinal skin scrapings were obtained from 322 asymptomatic volunteers. There were 261 males and 61 females ranging in age from 18 to 89; 136 were white, 134 were black, and 52 were Hispanic. Specimens were cultured on Sabouraud's glucose agar containing 500 micrograms ml 1 chloramphenicol, and incubated at 23-26 degrees C for up to 4 weeks. The overall incidence of T. beigelii colonization was 12.4%. However, this varied with patient's age, sex, race and socioeconomic background. The highest prevalence (27.1%) was found in black males who attended a Veterans Affairs hospital. The prevalence was lowest in females (1.6%), and no patients who attended a private clinic were colonized. It was concluded that T. beigelii colonizes normal skin with some regularity. PMID- 1880686 TI - Proliposomes of indomethacin for oral administration. AB - Indomethacin, a non-steroidal anti-inflammatory drug was encapsulated into liposomes composed of soyabean lecithin, cholesterol and stearylamine for oral administration. Liposomes of homogenous size distribution and higher entrapment efficiency were derived from effervescent granule based proliposomes. The efficacy of the oral route was studied by measuring ulcerogenic index and anti inflammatory activity using carrageenan induced paw oedema test in rats. The effervescent granule based liposomal products exhibited improved in vivo performance with reference to their cytoprotective and anti-inflammatory activities. PMID- 1880687 TI - Drug depots in lymph nodes: which carrier is most appropriate? AB - Different drug carriers for endolymphatic use (suspensions, emulsions, solutions, liposomes) were investigated in animal experiments to find the preparation which is best tolerated by lymph tissue, and which allows low release of highly concentrated drugs from nodal depots. The large unilamellar liposomes produced with detergent dialysis technique were found to be most appropriate for this purpose since they fulfill all the above criteria. PMID- 1880688 TI - Biopharmaceutical evaluation of a tablet dosage form made from ethyl cellulose encapsulated aspirin particles. AB - Ethyl cellulose encapsulated aspirin particles, suitable for preparation of direct compression tablets were prepared by the solvent evaporation method. Ethyl acetate was used as a solvent for the polymer in combination with a saturated solution of aspirin as the dispersing medium to prevent partitioning and drug loss. This resulted in a high yield of free-flowing, non-aggregated particles. In vitro-in vivo evaluations of the experimental aspirin tablets (made by direct compression of ethyl cellulose encapsulated particles) and three different commercial aspirin products (a conventional tablet, a timed-release tablet, and a timed-release caplet) were undertaken. Comparison of the dissolution in acidic media at pH 1.2 showed different release profiles for these products. While the conventional tablet and the timed-release caplet showed the highest and the lowest rate of release, respectively; the timed-release tablet and the experimentally made tablet revealed an intermediate rate and very similar release profiles. The cumulative urinary excretion data collected in a complete crossover study, using five healthy subjects further indicated that the experimental tablet has an in vivo availability identical to that of the timed-release tablet. PMID- 1880689 TI - Ampicillin-loaded liposomes and nanoparticles: comparison of drug loading, drug release and in vitro antimicrobial activity. AB - In this paper, we report the physico-chemical properties of negatively charged liposomes and of polyisohexylcyanoacrylate nanoparticles loaded with ampicillin. Although the carriers were of the same size (200 nm), drug-loading capacity was 20 times higher for nanoparticles than for liposomes. After freeze-drying or storage at +4 degrees C, no drug escaped from polymeric nanoparticles. On the other hand, in the same conditions, ampicillin leaked rapidly from liposomes. Drug release in foetal calf serum was gradual (of zero order) with nanoparticles, whereas it was rapid with liposomes. Finally, the antimicrobial activity of ampicillin-entrapped liposomes or nanoparticles was studied in vitro. PMID- 1880690 TI - Drug targeting using non-magnetic and magnetic albumin-globulin mix microspheres of mefenamic acid. AB - Optimum conditions for the preparation of non-magnetic and magnetic microspheres of albumin-globulin mix (alglomix) containing mefenamic acid have been standardized. The effect of various parameters has been investigated with regard to the appearance, yield, drug content and encapsulation efficiency. The physicochemical parameters of the microspheres such as density, particle size distribution, surface topography and wall thickness, as well as the magnetite contained within the magnetic microspheres, have been determined. The infrared spectroscopic analysis confirmed the encapsulation of the drug and absence of free drug on the surface of the microspheres. The X-ray diffraction analysis confirmed that the crystallinity of the drug remained unchanged indicating thereby that no complex formation had taken place between core and coat materials. The in vitro release profiles of the microspheres have been studied. An attempt has also been made to check the in vivo efficacy in rats. PMID- 1880691 TI - Interaction of poly(L-lysine-alt-terephthalic acid) microcapsules with fibrinogen. AB - Interaction of poly(L-lysine-alt-terephthalic acid) microcapsules with fibrinogen was investigated by measuring the degree of microcapsule disintegration, fibrinogen adsorption to microcapsules, and the zeta potential of microcapsules as a function of fibrinogen concentration in phosphate buffer solutions of pH 7.4 at different ionic strengths. A minimum concentration was found to exist for fibrinogen to cause disintegration of the microcapsules at any ionic strength, and at this fibrinogen concentration the fibrinogen adsorption levelled off and the zeta potential exhibited an abrupt change. Increases in the ionic strength of the medium and the surface hydrophobicity of microcapsules produced an increase in the degree of microcapsule disintegration by fibrinogen. These findings were interpreted as showing that the interaction of the microcapsules with the protein is not of an ionic nature but of a hydrophobic nature. PMID- 1880692 TI - Effect of solvents on the characteristics of rosin walled microcapsules prepared by a solvent evaporation technique. AB - Rosin microcapsules were prepared by a solvent evaporation technique using solvents with different rates of evaporation. Sulphadiazine was used as a model drug. The microcapsules were studied for their size, drug content, wall thickness, surface characteristics and in vitro release. The mean diameter increased and the drug content decreased as the rate of evaporation of the solvent increased. Fast evaporating solvents produced thick walled microcapsules with innumerable surface pores/cracks compared with slow evaporating solvents. PMID- 1880693 TI - Effect of solid dispersing agents on the formation of rosin microcapsules. PMID- 1880694 TI - A study on the zeta potential of microcapsules during ageing. AB - Gelatin, methylcellulose and agar microcapsules were prepared with and without suphadiazine. The zeta potential of these microcapsules was measured at regular intervals during ageing at 45 degrees C. An initial sharp rise in zeta potential is followed by a progressive decrease. Zeta potential could prove to be a useful parameter to study the changes occurring in the encapsulating material of microcapsules during ageing. PMID- 1880695 TI - Localized rifampicin albumin microspheres. AB - Rifampicin bearing albumin microspheres were prepared. The process variables which could affect the physical characteristics and in vitro release of the drug from the microspheres were optimized. Changes in the original size of the microspheres, namely swelling on exposure to buffer solution pH 7.2 and serum, were monitored. In vivo distribution studies on prepared microspheres revealed that 62 per cent of the drug could be localized in the lungs by controlling microsphere size. Hence, rifampicin bearing albumin microspheres can behave as a reservoir to build up higher local drug concentrations. PMID- 1880696 TI - Hydroxy-urea bearing albumin microspheres--preparation, characterization and evaluation. AB - Hydroxy-urea bearing albumin microspheres were prepared using the polymer dispersion method. Glycerol was used successfully in place of water as an internal phase of w/o emulsion, to prepare HSA based albumin microspheres. Silicone coated magnetite of nanometeric size was incorporated in the drug bearing microspheres. The process variables which could affect the physical characteristics with respect to in vitro and in vivo performance of the prepared microspheres were studied. The in vitro release of the drug from the microspheres followed a linear relationship when commulative per cent drug release was plotted against square root of time. Microspheres of average size 1-4 microns were studied for in vivo distribution and localization. It was established that 67 per cent of the drug enveloped in magnetic albumin microspheres could be localized in a rat tail target segment, on applying an external magnetic field of strength 8000 Oe. A remarkable stabilization of hydroxy urea in the prepared microspheres was recorded when t10% drug degradation was compared with the albumin microspheres prepared by a conventional emulsion polymerization method using water as an internal phase. PMID- 1880697 TI - Tantalum loaded silicone microspheres as particulate emboli. AB - Chloroform solutions of medical grade silicone resin were cured in an aqueous dispersion medium containing poly(vinyl alcohol) (PVA) as the drop stabilizer at 40-60 degrees C to generate smooth, spherical, elastic microspheres. The microspheres were encapsulated with tantalum powder to render them radiopaque. Tantalum loaded microspheres having diameter more than 1.00 mm could be prepared by this technique. Incorporation of radiopaques such as barium sulphate and methyl iothalamate resulted in the instability of the suspension giving rise to an agglomerated product. Microspheres were grafted with hydrophilic monomers such as 2-hydroxyethyl methacrylate (HEMA) and N-vinyl pyrrolidone (NVP) using ionizing radiation from a 60Co source in an effort to make their surfaces hydrophilic. While the graft yield was very little when HEMA alone was used for grafting, a combination of HEMA/NVP in a 1:1 ratio produced better graft yields resulting in improved surface hydrophilicity. The tantalum loaded microspheres were found to be very resistant to surface modification. Microspheres could be dispersed in water with the aid of small quantities of surfactants such as Tween 20. These microspheres may find use in particulate embolization. PMID- 1880698 TI - The next generation of moderator research in personality psychology. AB - The concept of a moderator variable has a long and checkered history in personality psychology. In this article I review the methodological and conceptual advances in recent moderator variable research. I then report the results of a number of empirical analyses of three newly proposed idiographic moderator variables: scalability, metatraits, and construct similarity, as well as the ipsatized variance index. The results of these analyses indicate that moderator effect sizes in personality can be expected to correspond to a correlation of about .10. I then consider two recent prescriptions, (a) aggregating trait-specific moderators into general ones, and (b) evaluating joint (e.g., triple interaction) moderator effects. Following these prescriptions did not increase the size of the moderator effects in these data. I conclude that moderator effects in personality will be small, and will thus be most reliably detected in very large samples with predictors that are strongly related to the criteria. Even small moderator effects can be important and interesting in the context of theory disconfirmation. However, moderator variables generally will not serve to transform weak relations among personality variables into strong ones. PMID- 1880699 TI - Narcissistic acts in everyday life. AB - This article presents a series of studies on narcissism, a personality syndrome receiving increasing theoretical and practical attention. Four empirical studies were carried out to (a) identify narcissistic acts in everyday life, (b) identify the acts subsumed by dispositions that are seen as central components of narcissism, (c) identify which acts and which dispositions are most and least central to narcissism, (d) test the hypothesis that the conceptually specified component dispositions of the narcissistic personality disorder indeed covary sufficiently to merit the designation of narcissism as a syndrome, (e) identify sex differences in the acts through which narcissism is manifested, (f) validate the Narcissistic Personality Inventory (a major personality instrument developed to assess narcissism), and (g) locate narcissistic act performance within each of three major taxonomies of personality psychology. PMID- 1880700 TI - The development of the sense of self in adolescence. AB - This study attempts to clarify the sense of self that may underlie the adolescent's subjective experience of identity. The initial orientation was provided by descriptions of three different modes of experiencing identity derived from a reanalysis of Loevinger, Wessler, and Redmore's (1970) ego development categories. Our goal was to replicate by a more direct method the Loevinger-derived descriptions. Specifically, we looked at whether the various aspects of the pre-identity mode ("Social Role Identity") and of the early identity mode ("Identity Observed") would in fact form different clusters and whether these clusters would differentiate early and middle adolescent groups. Participants were 24 sixth graders and 24 high-school seniors, equally divided by sex. In individual interviews they were asked questions concerning the main characteristics of the Identity Observed Mode. Six self scales were constructed from subjects' responses. Our two major hypotheses were strongly supported: (a) The two age groups differed dramatically on each of the self scales; and (b) the six self scales highly correlated with each other. Moreover, clusters of responses could be constructed that model the a priori descriptions of identity modes and that sharply separate the two grades. PMID- 1880701 TI - Adjustment, depression, and minimal goal setting: the moderating effect of performance feedback. AB - In this study I tested hypotheses about changes in expectancy and minimal goal statements and the relations of these variables to adjustment. Seventy-seven male college students completed the Rotter Incomplete Sentences Blank and the Beck Depression Inventory and subsequently received success or failure feedback on tasks for which they provided expectancy and minimal goal statements. Expectancies and minimal goals changed differently, relative to each other, as a function of performance feedback. Modest relations of adjustment and dysphoria with minimal goals were found, but these were moderated by performance feedback: Under failure, poorer adjustment and greater dysphoria were associated with higher minimal goals; under success, poorer adjustment and greater dysphoria were associated with lower minimal goals, contrary to a widely held hypothesis. Moreover, although the effects of adjustment and dysphoria on minimal goal setting were similar in strength and direction, these effects were independent of each other. Thus, adjustment-minimal goal relations must be understood in light of situational parameters and may reflect two processes, only one of which is related to mood. PMID- 1880702 TI - An interpretation of the Hill equation: time course of diuretic response after furosemide administration in man. AB - Response function, which correlates pharmacologic response intensity and the drug concentration, is defined assuming that the biophase (or the site of action) is consisted of the elements responsive to the drug, each of which is in a responding or non-responding state depending on the drug concentration in the biophase. The Hill equation, which has been widely used without a definite rationale, for correlation between pharmacologic response intensity and drug concentration is revealed as an approximate equation of the response function. Diuretic data obtained after administration of furosemide and reported previously are used for conformity assessment of the response function. PMID- 1880703 TI - Hepatic drug metabolizing activity in rats with carrageenan-induced inflammation. AB - Effect of carrageenan-induced inflammation on hepatic drug metabolism was studied in male and female Wistar rats. One day after treatment of male and female Wistar rats with carrageenan (1%, 0.1 ml, s.c.) (i) a prolongation of the duration of sleeping time induced by hexobarbital (100 mg/kg, i.p.), (ii) decreases biotransformation of hexobarbital, aminopyrine and ethylmorphine in the hepatic 9000 x g supernatants (S-9) and (iii) a decrease in cytochrome P-450 content were observed in males but not female rats. However, carrageenan treatment did not alter aniline hydroxylase activity in animals of either sex. Carrageenan also suppressed induction of hexobarbital, aminopyrine and ethylmorphine metabolism by phenobarbital treatment, and depressed the induction of hepatic S-9 cytochrome P 450 content caused by phenobarbital treatment. These data show that there is a sex-related difference in the ability of carrageenan to alter hepatic drug metabolism, which is substrate-specific, in the rats. PMID- 1880704 TI - The relationship of salicylate lipophilicity to rectal insulin absorption enhancement and relative lymphatic uptake. AB - The sodium salts of the 3,5-dichloro, 3,5-dibromo-, 3,5-diiodo-, and 5-methoxy- analogs of salicylic acid have been evaluated as enhancers of rectal insulin absorption. A relationship was found between adjuvant potency and relative lipophilicity. Maximal adjuvant activity was obtained with 0.1 M 3,5 dichlorosalicylate. Higher concentrations (0.15 M) of 3,5-diiodosalicylate produced a decline in adjuvant activity, which may be associated with extraction of specific cellular proteins. This may indicate the existence of an optimal salicylate lipophilicity for adjuvant efficacy. Relative adjuvant activity was found to be related to the lymph:plasma absorption ratio of [125I]insulin. Lymphatic uptake of insulin was not related to lymph flow rate. PMID- 1880705 TI - Bioavailability of cyclandelate from capsules in beagle dogs and dissolution rate: correlations with bioavailability in humans. AB - The bioavailability in beagle dogs and the dissolution rates of cyclandelate from five capsule preparations commercially available in Japan were measured. One of the capsules that showed an extremely low bioavailability in humans also showed the lowest bioavailability in beagle dogs, although the difference in bioavailability with the highest preparation was smaller than in humans. A significant correlation was obtained between the results of the studies in humans and beagles. However, the power of the test using beagles was extremely low in comparison with that in the human study. Food enhanced the bioavailability of cyclandelate from the capsules having the highest and lowest bioavailability in the fasted state in beagles as observed in the human study previously. The bioinequivalence of the cyclandelate capsules detected in the fasted state disappeared in the fed state in the beagle dog study, while the bioinequivalence still remained in the non-fasted state in human subjects. Thus bioequivalence testing in the fed state led to different results in both species. The most poorly bioavailable capsule in both species in the fasted state showed a slow dissolution rate by several dissolution methods with moderate stirring. In order to obtain a good correlation with in vivo bioavailability, a large volume of test solution and addition of Tween 80 were required. Extensive growth of whiskers (needle-like crystals) was observed in the entire capsule mass having the lowest bioavailability. PMID- 1880706 TI - Site-selective oxidation of strychnine by phenobarbital inducible cytochrome P 450. AB - The metabolism of strychnine was studied using liver microsomes of rats treated with phenobarbital or 3-methylcholanthrene (MC). The phenobarbital-treatment resulted in 7.9-fold and 4.8-fold increases in 2-hydroxylation and N-oxidation of strychnine, respectively. The formation of 16-hydroxystrychnine, strychnine 21,22 epoxide and 22-hydroxystrychnine was induced about 2-fold. MC-treatment resulted in only 1.4-fold induction of each oxidation activity. In addition, strychnine 2 hydroxylation activity was markedly induced in liver microsomes of phenobarbital treated mice, guinea pigs, rabbits and dogs (2.5-10.5-fold). Induction of N oxidation activity was also higher than that of the three other oxidation activities. A reconstituted system of strychnine metabolism using cytochrome P 450 isozymes, P-450I (P450IIB1) and P-450II (P450IIB2), purified from liver microsomes of phenobarbital-treated rats showed significantly high and selective activities towards 2-hydroxylation and N-oxidation of strychnine. This characteristic metabolism of strychnine appears to occur in common with interspecies P450IIB gene subfamily. The pH Optima of 2-hydroxylation and N oxidation of strychnine were between 8.4 and 8.6 in the microsomes of phenobarbital-treated rats, while that of N-demethylation of benzphetamine, a typical substrate of phenobarbital-inducible cytochrome P-450, was between 7.4 and 7.6. In a reconstituted system with P-450I, strychnine oxidation was little affected by pH change, while benzphetamine N-demethylation activity was decreased in the alkaline side. Among several oxidations tested, only ethylmorphine N demethylation underwent the same pH effect as did strychnine oxidation with the microsomes and reconstituted system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880707 TI - Melatonin-induced enhancement of antibody-dependent cellular cytotoxicity. AB - Antibody-dependent cellular cytotoxicity (ADCC) is a lytic mechanism in which a specific antibody acts cooperatively with leukocytic effector cells to induce target cell lysis. In this paper, the effect of exogenous melatonin on ADCC was examined. It was found that two evening intravenous injections of melatonin (1 mg/kg b.w.) was sufficient to enhance the capacity of splenocytes to mediate ADCC. This augmented activity returned to normal levels by day 6. Moreover, the opioid antagonist, naloxone, was unable to inhibit the ADCC enhancement, suggesting that melatonin did not operate through a naloxone-sensitive opiatergic mechanism. These results further support the modulatory action of melatonin on immune responses. PMID- 1880708 TI - Circadian and seasonal rhythms of melatonin production in mules (Equus asinus x Equus caballus). AB - The present study describes the patterns of melatonin production in the mule (Equus asinus x Equus caballus). Blood was sampled hourly for 24 h from eight mule mares in spring and fall. The data obtained show the presence of a circadian rhythm of production of melatonin, with highest values during the dark phase both in spring and fall. In fall the nightly rise of melatonin production begins earlier in the dark phase and reaches higher quantitative levels than in spring. The morning decline of melatonin production is similar in the two seasons. Maximal levels of nightly melatonin production in the mule are about 10 x higher than those described in the horse. The results reported here indicate the persistence of brain structures able to receive and transduce environmental signals in the mule, a genetically sterile mammalian hybrid. PMID- 1880709 TI - Melatonin, a suppressor of spontaneous murine mammary tumors. AB - The effect of prolonged, oral melatonin treatment on spontaneous mammary tumor development in female C3H/Jax mice was studied. Melatonin was administered at a dose of 25 micrograms/mouse/day from 21 to 44 days of age and 50 micrograms/mouse/day from day 45 onwards. By the age of 12 months, 62.5% of control animals developed tumors as opposed to 23.1% in the melatonin treated group (P less than 0.02). In both control and treated mice, the thoracic pairs of mammary glands were obviously more susceptible to spontaneous mammary tumor development, as at least 50% of the total tumors developed in this region. Reduction in submaxillary and pituitary gland weights of treated animals was observed at necropsy (P less than 0.001). Decreased serum 17-beta-estradiol (E2) levels in melatonin treated mice (P less than 0.05) and a marked reduction in [3H]thymidine incorporation into DNA of melatonin-treated mammary glands (P less than 0.02) positively correlated with the sparse mammary gland development seen in these mice. These observations indicate that at the given dose level, melatonin modulates the degree of development of the mammary epithelium, subsequently reducing spontaneous mammary tumor incidence in these high risk mice. PMID- 1880710 TI - Urinary 6-sulphatoxymelatonin, an index of pineal function in the rat. AB - The objective of this study was to apply the radioimmunoassay for 6 sulphatoxymelatonin (aMT6s) to rat urine, and use it to study the source of aMT6s. The radioimmunoassay was found to have acceptable within- and between assay variation, excellent specificity, and good parallelism between the standard and unknown. Because urine is highly contaminated we assessed whether preliminary purification was required and established that it was unnecessary. Using this assay a 24-hr rhythm in 6-sulphatoxymelatonin output was seen in pools of urine harvested at 3-hr intervals from Wistar rats on LD 12:12. The nocturnal rise in aMT6s was abolished by constant light. In contrast pinealectomy lowered aMT6s output significantly throughout both dark and light. This study confirms previous studies indicating that the pineal is the major source of 6-sulphatoxymelatonin. It is concluded that urinary 6-sulphatoxymelatonin as measured by radioimmunoassay is a valid measure of pineal gland activity in the rat. PMID- 1880711 TI - Failure of single electroconvulsive shock to affect daytime melatonin production in rats. AB - It has been reported that, in the rat, different types of stressful procedures increase daytime melatonin production. Electroconvulsive shock (ECS) has been shown not to affect daytime pineal melatonin in rats killed 9 hr after its administration. It is possible that the long-lasting interval between the ECS administration and the sacrifice of the animals obscured an effect of the stressful procedure. In the present study, the effects of acute ECS on daytime melatonin production were evaluated in both ECS- and sham-treated rats killed 30, 60, 120, and 240 min after treatment. As compared with the sham-treated animals, rats receiving acute ECS (80 mA, 0.5 sec) did not show any significant difference in either pineal or serum melatonin levels at any time point after treatment. These data indicate that single ECS does not affect daytime melatonin production in the rat and suggest that the pineal gland may respond differently to the various stressful procedures. PMID- 1880712 TI - The effects of benzodiazepines on basal and isoproterenol-stimulated N acetyltransferase activity by the rat pineal gland, in vivo and in vitro. AB - The present study examined the effects of "peripheral," "central," and "mixed" benzodiazepine agonists and antagonists on the nocturnal rise in rat pineal NAT activity in vivo and the isoproterenol-stimulated NAT activity of pineals in organ culture. Administration of the central agonist clonazepam or the mixed agonist-antagonist diazepam, 4 hr after dark, at a dose of 25 mg/kg each, inhibited nocturnally elevated NAT 20 min later, while this same dose of the peripheral agonist RO 54864 elevated NAT activity. In a second study these agents were administered in vivo 1 hr before dark, at a dose of 3, 10, or 25 mg/kg i.p. and tested 4 hr after dark for in vitro rat pineal NAT activity. None of these agents affected NAT activity at the 3- or 10-mg/kg dose, but RO 54864 25 mg/kg did induce elevated activity. In a third study, all of these agents prolonged the time period for NAT induction by isoproterenol in rat pineals cultured for 48 hr before stimulation. The data suggests that benzodiazepine stimulation of NAT activity in vitro is not specific to "central" or "peripheral" benzodiazepine receptors and that inhibition of melatonin production in vivo occurs either at some step before NAT induction or is involved with the inhibition of pineal HIOMT activity. PMID- 1880713 TI - Host-controlled modification and restriction as a criterion of evaluating the therapeutical potential of Pseudomonas phage. AB - The recently isolated phages phi ST3 and phi ST1 were compared as to their lysis behaviour in about 100 different P. aeruginosa strains. The growth of phi ST3 varies greatly in different host strains. We demonstrated one case of "non classical", host-dependent modification and restriction. Here the capability to adsorb, and consequently to reproduce in a given host strain differs, depending on which modification the phage acquired in its former host. The DNA-containing phage phi ST1 displays stable lysis properties in the majority of the host strains. This makes phi ST1 a candidate for therapeutic phage preparations. One of the reasons for stable lysis properties is the apparent selection against recognition sites of restriction enzymes in its genome. PMID- 1880714 TI - Steric course of the N-methylation in the biosynthesis of ergot alkaloids by Claviceps purpurea. AB - Using the chiral methyl group methodology, the methylation step in the biosynthesis of ergot alkaloids catalyzed by the enzyme AdoMet:dimethylallyltryptophan N-methyltransferase was found to proceed with net inversion of methyl group configuration. The enzyme thus conforms to the majority of methyltransferases studied which mediate a direct SN2 transfer of the methyl group from AdoMet to the acceptor nucleophile in a ternary enzyme substrate complex. PMID- 1880715 TI - A solid-phase enzyme immunoassay for the detection of tetanus toxin using human and murine monoclonal antibodies. AB - Three human and three murine monoclonal antibodies were tested for their reactivity to tetanus toxin and toxoid and used to establish an enzyme immunoassay specific for tetanus toxin. The dissociation constants of the monoclonal antibodies were between 3.91 x 10(-9) and 8.48 x 10(-12). Two human monoclonal antibodies recognized conformation determinants on the toxin, whereas the others reacted to the heavy chain. Only a combination of antibodies of the two species allowed the development of an enzyme immunoassay for the detection of tetanus toxin with a lower detection limit of 1.2 micrograms/l. PMID- 1880716 TI - Phyllosphere and phylloplane fungi of qat in Sana'a, Yemen Arab Republic. AB - Eighty six species belonging to thirty one genera were collected from the qat phyllosphere (30 genera and 78 species) and phylloplane (20 genera and 64 species) of 24 varieties tested. In the phyllosphere the most frequent genera were Cladosporium, Aspergillus and Alternaria followed by Penicillium, Drechslera, Fusarium, Curvularia, Phoma and Chaetomium. From the preceding genera the most prevalent species were C. herbarum, C. macrocarpum, A. niger, A. flavus, A. alternata, A. phragmospora, P. citrinum, P. notatum, D. spicifera, D. halodes, D. hawaiiensis, F. oxysporum, F. moniliforme, C. lunata, P. humicola, P. herbarum and C. globosum. In the phylloplane the order of genera frequency was more or less the same, while the most common species were C. herbarum, C. sphaerospermum, A. niger, A. flavus, A. alternata and A. tenuissima. PMID- 1880717 TI - Disposition of methylprednisolone and its sodium succinate prodrug in vivo and in perfused liver of rats: nonlinear and sequential first-pass elimination. AB - The disposition of methylprednisolone (MP) and its prodrug succinate ester, methylprednisolone sodium succinate (MS), were examined both in vivo and in situ (perfused livers) in rats. In vivo studies included iv and oral dosing of 10 or 50 mg/kg of MP in both forms, while liver perfusion involved initial perfusate concentrations of 5 and 25 micrograms/mL of either compound. Steroid concentrations were measured by HPLC. In the intact rat, clearance (CL) values of both compounds were high, twice the hepatic plasma flow, and decreased by one half after the high dose, indicating nonlinear kinetics. The volumes of distribution of MS and MP were essentially constant with dose. Incomplete availability of MP from iv MS (52-55%) and from the oral dose (10%) was found. Sequential first-pass metabolism was investigated in situ. Extensive hepatic extraction of MP (84%) occurred at the low dose, but decreased to 48% at the high dose, supporting in vivo observations of high CL and nonlinearity. Extraction of MS was also high (83%), but MP availability was slight (8%). The MS and MP data were fitted to a sequential first-pass model yielding an average fraction of MS metabolized-to-MP value of 0.22. The prodrug MS and the active metabolite MP thus demonstrate both systemic and hepatic nonlinearity in rats, and the low availability of MP from iv MS was due, in part, to sequential first-pass elimination. This factor is more extensive in rats than in other species. PMID- 1880718 TI - Characterization of the degradation products of luteinizing hormone releasing hormone. AB - The degradation products of luteinizing hormone releasing hormone [LH/RH; 1; gonadorelin releasing hormone (GnRH); less than Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg Pro-Gly-NH2] were determined in aqueous solution (pH 6.5) at 25, 37, 50, and 80 degrees C. The predominant route of degradation involved the cleavage of the less than Glu-His and Trp-Ser peptide bonds to give peptides 5-9 and hydrolysis of the terminal Gly-NH2 to the free acid form in peptides 4 and 10. Racemization of the serine and histidine residues to give peptides 2 and 3 was a second route of degradation. PMID- 1880719 TI - Follicles play an important role in percutaneous absorption. AB - The relative importance of stratum corneum and follicles in percutaneous absorption is not fully understood. In order to quantitatively investigate the importance of the transappendageal route, we have previously developed a model of skin without follicles regrown dorsally on the hairless rat. Percutaneous absorption was compared, using a diffusion cell, in appendage-free skin relative to normal skin, and a predominant role of follicles for in vitro diffusion of [3H]hydrocortisone was noted. Results presented here of in vitro diffusion of tritiated hydrocortisone, niflumic acid, caffeine, and p-aminobenzoic acid, applied in acetone, confirm that appendageal diffusion is the major pathway in hairless rat skin. In the absence of follicles, the steady-state flux and the amounts diffusing in 24 or 48 h are 2-4 times lower than in normal skin. These results were confirmed in a second model in which diffusion of [3H]hydrocortisone was studied on skin samples taken one day after birth, at which time rat skin is still devoid of follicles, relative to five-day postnatal skin samples, in which follicles are fully developed. The steady-state flux and the total diffusion in 24 h were fivefold lower in follicle-free skin. These results support the view that follicles may have a far greater importance in percutaneous absorption than is generally assumed. PMID- 1880720 TI - Lyotropic liquid crystals and the structural lipids of the stratum corneum. AB - Lipids were extracted from human stratum corneum and the remaining corneocytes were reaggregated with different lyotropic liquid crystals. Water transport through the reaggregated stratum corneum was determined using a diffusion chamber according to Smith and Blank. The permeability constant for the reaggregated stratum corneum with natural lipids was 25-40% lower than that with the surfactant liquid crystals, but there was no significant difference between different liquid crystals. PMID- 1880721 TI - Effect of food on bioavailability of pseudoephedrine and brompheniramine administered from a gastrointestinal therapeutic system. AB - The purpose of this study was to determine how a high-fat meal affects the delivery and absorption of pseudoephedrine and brompheniramine maleate when delivered from a gastrointestinal therapeutic system (GITS). This study was a randomized, complete crossover trial with 12 healthy male volunteers who were given single doses of the 24-h GITS under fed and fasted conditions. Pharmacokinetic parameters for both drugs were comparable between fed and fasted treatments, except for a shorter time to maximum concentration of pseudoephedrine for fed subjects (p = 0.002). Bioavailability of pseudoephedrine was 91% for fed relative to fasted treatment; for brompheniramine it was 89%. These results indicate that codelivery of the two drugs from the GITS is reliable and prolonged, and that the resulting absorption of pseudoephedrine and brompheniramine is minimally affected by food. PMID- 1880722 TI - Biodegradable microspheres. XIII: Immune response to the DNP hapten conjugated to polyacryl starch microparticles. AB - Polyacryl starch microparticles are being investigated for use as drug carriers, especially in the treatment of intracellular parasitic diseases. The purpose of this work was to investigate the possible immune response to drugs coupled to the microparticles, using the dinitrophenyl group (DNP) as a model. The humoral immunogenicity of DNP hapten-conjugated polyacryl starch microparticles has been examined in mice. Microparticle:hapten complexes with different biodegradability were tested, as well as different dosages and routes of administration. Two DNP derivatives, Lys(DNP) and Leu-Ala-Lys(DNP), were coupled to microparticles. It was shown that Lys(DNP) was released from the particles by lysosomal enzymes only from the conjugate with the tripeptide DNP derivative. The DNP conjugated to the particles via the biodegradable Leu-Ala-Lys arm induced only a weak immune response without memory. No response was detected after injection of the Lys(DNP) microparticles. Thus, there should be no major immunological obstacles in using drug:microparticle complexes in the treatment of, for example, parasitic diseases. PMID- 1880723 TI - Relation between structure and antimicrobial activity of 2-(N,N,N trialkylammonio)alkyl hydrogen phosphates. AB - A series of phosphobetaines [2-(N,N,N-trialkylammonio)alkyl hydrogen phosphates], having different alkyl chains and a methylene bridge separating the phosphate and ammonio group, was investigated in order to provide a new antimicrobial agent. Maximal activity was obtained with the compound having a hexadecyl group as a long-chained alkyl group, two methyl groups as short-chained alkyl groups, and a dimethylene bridge as an intercharge distance. In contrast, sodium 2-(N-hexadecyl N-methylamino)ethyl hydrogen phosphate, 2-(N-hexadecyl-N,N-dimethylammonio)-1 hydroxyethyl iodide, and N-octadecyl-N,N-dimethylammonio acetate showed decreased activity, indicating that the presence of a phosphobetaine moiety was essential for activity. Thus, 2-(N-hexadecyl-N,N-dimethylammonio)ethyl hydrogen phosphate has been found to possess strong antimicrobial activity and a broad antimicrobial spectrum against nine kinds of bacteria (e.g., fungi, yeast, gram-negative and gram-positive bacteria), which are comparable with those of chlorhexidine digluconate. PMID- 1880724 TI - Disposition of the diastereoisomers quinine and quinidine in the ovine fetus. AB - The disposition of the diastereoisomers quinine and quinidine was investigated in the near-term pregnant ewe. Five sheep were administered quinine and quinidine separately in random order by a combination of bolus and 30-h iv infusion. On a subsequent occasion, four of the five sheep were also administered the two drugs simultaneously. After separate dosage, systemic clearance of quinine tended to be greater than that of quinidine (714 +/- 299 versus 422 +/- 146 mL/min, p = 0.08). Maternal renal clearance exhibited no stereoselectivity and represented less than 2% of total clearance. Simultaneous administration did not alter the disposition of either drug in the mother. After separate dosage, fetal total concentrations (Cf) of quinine and quinidine were substantially lower than maternal total concentrations, as reflected in Cf:Cm ratios of 0.15 +/- 0.06 versus 0.10 +/- 0.08, respectively. Similarly, fetal unbound concentrations (Cfu) were substantially lower than maternal unbound concentrations (Cmu; Cfu/Cmu = 0.46 +/- 0.09 for quinine and 0.23 +/- 0.09 for quinidine). This indicates the presence of fetal elimination of both isomers. Fetal renal clearances of quinine and quinidine were similar (0.34 +/- 0.24 mL/min versus 0.38 +/- 0.24 mL/min) and less than that of endogenous creatinine, indicating the absence of net renal tubular secretion. After simultaneous dosage of quinine and quinidine, Cf:Cm (0.48 +/- 0.24 and 0.31 +/- 0.19, respectively) and Cfu:Cmu (0.73 +/- 0.14 and 0.52 +/- 0.20, respectively) were greater than for separate dosages. Fetal renal clearance of both drugs was unchanged, suggesting that the higher Cfu:Cmu ratios after simultaneous dosage were due to mutual inhibition of the fetal metabolism of these drugs. PMID- 1880725 TI - Prediction of solute sorption by polyvinyl chloride plastic infusion bags. AB - The time course of the sorption of drugs by polyvinylchloride infusion bags has been approximated using a diffusion model in which the plastic is assumed to act as an infinite sink. This model appears to be suitable for estimation of storage times relevant to clinical usage and enables the magnitude of the uptake in a specific time to be described by a single parameter, referred to as the sorption number. This parameter is defined by the plastic-infusion solution partition coefficient, the diffusion coefficient in the plastic, the fraction un-ionized in solution, the volume of the infusion solution, and the surface area of the plastic. An approximation of the model allows a ready estimation of the sorption number from the fraction remaining in solution at a given time. The sorption number can be extrapolated to allow prediction of the effects of time, plastic surface area, solution volume, and solution pH on fractional solute loss. A reasonable correlation was established between the logarithm of this parameter and the logarithm of the octanol-water partition coefficients of various solutes. The model allows the fraction of a solute remaining in a plastic infusion bag at a given storage time to be estimated from the octanol-water partition coefficient of the solute and other readily available data. PMID- 1880726 TI - Determination of ibuprofen in ointments by reversed-phase liquid chromatography. AB - A selective reversed-phase HPLC method for the determination of ibuprofen in different ointment bases is described. Following a simple dilution step, the drug was separated from interfering compounds on an octadecylsilica column protected by a precolumn. A mobile phase of aqueous tetrahydrofuran buffered by phosphate was used. Detection was monitored at 219 nm. After each 10 injections of lipophilic samples, the columns were washed with tetrahydrofuran and n-hexane. Recoveries of ibuprofen from a new pilot preparation spiked to contain 4, 5, and 6% of the drug were 100.4, 100.3, and 99.7%, respectively. The precision at each concentration was less than 0.8%. The analysis of ibuprofen degeneration products showed that the method also provides an indication of the stability of the drug. PMID- 1880727 TI - Kinetics of the acid hydrolysis of diazepam, bromazepam, and flunitrazepam in aqueous and micellar systems. AB - A kinetic study of the acid hydrolysis of aqueous diazepam, bromazepam, and flunitrazepam was carried out at 25 degrees C using a spectrophotometric method. For diazepam and flunitrazepam, the experimental pseudo first-order rate constant decreased as the acid concentration was increased. The contrary behavior was found in the case of bromazepam. A kinetic scheme that includes the hydrolysis reaction of both protonated and nonprotonated species of the drug can account for these results. Also, the kinetics of the acid hydrolysis of the same drugs in the presence of micellar aggregates [nonionic polyoxyethylene-23-dodecanol (Brij 35); cationic cetyl trymethyl ammonium bromide (CTAB); and anionic sodium decyl (SdeS), dodecyl (SDS), and tetradecyl (STS) sulfate] was studied at 25 degrees C. Negligible effects were observed in the cases of nonionic and cationic micelles. Anionic micelles produced an inhibitory effect in the reaction velocity. This effect increased as the hydrophobic nature of the surfactant increased. All these facts are interpreted quantitatively by means of a pseudophase model. PMID- 1880728 TI - Effect of formulation solubility and hygroscopicity on disintegrant efficiency in tablets prepared by wet granulation, in terms of dissolution. AB - The effect of tablet formulation solubility and hygroscopicity on the dissolution efficiency of three "super disintegrants" (sodium starch glycolate, crospovidone, and croscarmellose sodium) in tablets prepared by wet granulation was investigated. Lactose, calcium phosphate dibasic, sorbitol, and naproxen sodium, alone or in combination, provided varying degrees of solubility and hygroscopicity in the formulations. To monitor in vitro dissolution, 1% p aminobenzoic acid was added to the formulation as a tracer. The results indicate that highly soluble and/or hygroscopic ingredients decrease the effectiveness of super disintegrants in promoting in vitro dissolution. The greater the overall hygroscopicity and solubility of the tablet formulation, the larger the decrease in the efficiency of the super disintegrant. PMID- 1880729 TI - Influence of solute structure on deviations from the log-linear solubility equation in propylene glycol:water mixtures. AB - The solubilities of the methyl, ethyl, propyl, and butyl esters of p-hydroxy- and p-aminobenzoates have been determined in propylene glycol:water mixtures. The log of the observed solubility data in propylene glycol:water mixtures was examined for deviations from the following equation: In Xi = f In (Xc) + (1 - f) In (Xw), where Xi is the calculated mole fractional solubility of the solute, f is the volume fraction of cosolvent, Xc is the observed mole fractional solubility in the neat cosolvent, and Xw is the solubility in water. In each case, the deviations from the predicted solubilities demonstrated a characteristic pattern. Positive deviations were observed at high volume fractions of cosolvent, while negative deviations were observed at low volume fractions. The magnitude of the deviations at low volume fractions of cosolvent was related to the carbon chain length within each group of esters. A similar phenomenon was not observed at high volume fractions of cosolvent; however, the magnitude of the deviations was dependent on the nature of the polar group on the ester. The data are interpreted in terms of the possible effects of solvent structure on the solubility of the solutes. PMID- 1880730 TI - Enhancement of dissolution and absorption of mefenamic acid by egg albumin. AB - The dissolution behavior and absorption of mefenamic acid following oral and rectal administration from drug:egg albumin solid dispersions have been studied in comparison with those of the drug alone. The interaction of drug with egg albumin in aqueous solution and solid state were examined by solubility analysis, dialysis experiments, and X-ray diffractometry. The results showed that the dissolution rate of mefenamic acid, and also the release of drug from witepsol H 15 suppositories, were significantly increased by using egg albumin:drug solid dispersions. Although egg albumin:drug solid dispersion enhanced the mean serum levels and the area under serum concentration-time curves after oral and rectal administration compared with those of the drug alone, no significant differences were found between the mean residence time values of drug and its solid dispersion. It was also noted that the extent of bioavailability of mefenamic acid and its solid dispersion following oral administration was significantly greater than that following rectal administration. PMID- 1880731 TI - A system approach to pharmacodynamics. III: An algorithm and computer program, COLAPS, for pharmacodynamic modeling. AB - Many pharmacodynamic (PD) models may be generalized in the form E(t) = N(L[c(t)]), where E(t) is a recorded effect response, c(t) is a sampled drug level, N is a nonlinear autonomic function, and L is a linear operator that commonly is a convolution operation. The NL class of PD models includes the traditional effect compartment PD models as a subclass, but is not limited to such models. An algorithm and computer program named COLAPS, based on system analysis principles and hysteresis minimization, that enable N and L to be empirically determined for the NL class of models without addressing specific kinetic structure aspects ("model independence") are presented. The kinetic concepts of biophase conduction and transduction functions are used by COLAPS. Such an approach is more general than the effect compartment approaches because it does not assume first-order transport principles. The pitfalls of hysteresis minimization in PD modeling are discussed and the procedures taken by COLAPS to avoid these pitfalls are outlined. A transformation technique prevents improper convergence to a point. A novel reparameterization scheme is introduced that maximizes the flexibility of the kinetic functions and extends the generality of the analysis. Inequality function constraints are maintained without the need for troublesome constrained nonlinear optimization procedures. Usage of the COLAPS program is illustrated in the analysis of the PD of amobarbital. The COLAPS program resulted in an excellent minimization of the effect versus biophase level hysteresis. The biophase conduction function, the biophase drug level (normalized), and the transduction curve were determined. The transduction curve showed clear biphasic behavior. PMID- 1880732 TI - Kinetics of transition of anhydrous carbamazepine to carbamazepine dihydrate in aqueous suspensions. AB - When suspended in water, anhydrous carbamazepine (C15H12N2O; 1) was transformed to carbamazepine dihydrate (C15H12N2O.2H2O; 2). Compound 1 was dispersed in water at 25 degrees C, and an aliquot of the slurry was taken at periodic intervals and immediately filtered under conditions which removed all the physically bound water from the solid. The weight fractions of 1 and 2 in the solid were quantified by two methods: (a) by determining the weight loss on drying the solid at 60 degrees C under reduced pressure to a constant weight and (b) by a quantitative powder X-ray diffraction technique. There was good agreement between the above two methods. More than 95% (w/w) of 1 was converted to 2 in 1 h and the decrease in the weight fraction of 1 with time was approximately a first-order process. PMID- 1880733 TI - A body surface area nomogram based on the formula of Gehan and George. PMID- 1880734 TI - A compartment model for percutaneous drug absorption. PMID- 1880735 TI - Pharmacokinetics of intranasal drug administration: the influence of some biological factors. PMID- 1880736 TI - Relationships between the area under the first moment curve after single bolus injection and the integral of plasma concentrations after constant-rate intravenous infusion. PMID- 1880737 TI - Cardiac disease. PMID- 1880738 TI - Postpartum maternal adaptation. PMID- 1880739 TI - Care of the pregnant patient with a pacemaker. AB - This article has reviewed cardiovascular adaptations to pregnancy and parturition. It has presented a basic overview of pacemaker supported cardiovascular function and related that to pregnancy. It has summarized 22 previously reported cases of pregnancy among women with pacemakers and reported yet another such case. The following conclusions can be drawn: The pregnant woman with a pacemaker, especially one that is not rate-responsive, faces risks for destabilized cardiovascular adaptation during the course of pregnancy, labor, and delivery. Individualized, ongoing nursing assessment focusing on detecting early signs of compromised cardiac output is critical in order to avoid maternal as well as fetal distress. Pregnancy has a high probability of coming to successful conclusion when professionals anticipate potential complications and monitor for early signs of difficulty. Providing care for the woman with a pacemaker presents many challenges to the perinatal nursing staff providing antepartum, intrapartum, and postpartum care. The woman, the fetus or newborn, and the family are best cared for by a multidisciplinary team whose members bring specialized knowledge and skill to bear on the needs she and the fetus present. PMID- 1880740 TI - Valvular disease in pregnancy. AB - The hemodynamics of pregnancy make this a time of great risk for the cardiac patient. RHD is still the most commonly seen lesion in women of childbearing age. When the mitral valve becomes stenotic, it severely limits flow into the left ventricle, resulting in a buildup of pressure in the left atrium and possibly the pulmonary artery. These patients are at risk for pulmonary edema and a decrease in cardiac output. Intrapartum care must focus on meticulous fluid management and alleviation of pain and anxiety to avoid the tachycardiac effect. PMID- 1880741 TI - ECG interpretation for obstetric nurses. AB - Obstetric nurses are not routinely called on to perform continuous cardiac monitoring or ECGs. However, obstetric nurses will be caring for most pregnant women with cardiac complications. Basic and advanced ECG courses and Advanced Cardiac Life Support (ACLS) courses are offered at most hospitals. Obstetric nurses are encouraged to take advantage of these courses, as even nurses in Level I institutions are caring for patients on continuous ECG monitors. A basic understanding of the ECG is expected of all nurses. Obstetric nurses are encouraged to participate in an ACLS program. Full reviews of the anatomy, physiology, and electrical pathways are available in numerous texts. PMID- 1880742 TI - Myocardial infarction during pregnancy. AB - Although myocardial infarction during pregnancy is not a common event, its occurrence is associated with significant morbidity and mortality for both mother and fetus. Multidisciplinary collaboration is required to individualize care. The presence of two patients (mother and fetus) must be acknowledged and the cardiovascular stress imposed by pregnancy and birth must be recognized. Nurses who care for these patients are required to integrate both cardiac and obstetrical knowledge and attend to psychosocial as well as physical needs. The impact of MI on maternal tasks of pregnancy, coping ability, maternal-fetal attachment, and adjustment to parenthood are certainly great but are beyond the scope of this article. PMID- 1880743 TI - Cardiovascular assessment of the neonatal heart. AB - Identification of the newborn with CHD continues to be a challenge. Neonatal nurses are frequently the first to make an assessment suggestive of cardiac disease. Collaborative efforts to make a differential diagnosis begin with a thorough cardiac assessment. PMID- 1880744 TI - The postoperative cardiac infant: physiologic basis for neonatal nursing interventions. AB - The care of the postoperative cardiovascular neonate is complex and multifaceted. A comprehensive understanding of physiology, pathology, and appropriate interventions is necessary for a successful outcome. The neonatal nurse plays a pivotal role in the collaborative management of these neonates to support delivery of quality care. PMID- 1880745 TI - Pharmacologic interventions for the neonate with compromised cardiac function. AB - The developmental aspects of myocardial performance must be considered when pharmacologic agents are used to support the neonate with compromised cardiac function. Neonatal cardiovascular function is characterized by a limited preload reserve, decreased ventricular compliance, limited contractile reserve, and CO that is primarily dependent on the HR. Nurses caring for these neonates need a baseline understanding of normal cardiovascular physiology to evaluate the effectiveness of pharmacologic interventions to augment CO. Neonatal nurses play a pivotal role in the therapeutic management of pharmacologic interventions to provide safe, high quality care for the sick neonate. PMID- 1880746 TI - Analysis of a below-knee patellar tendon-bearing prosthesis: a finite element study. AB - In this study, a finite element (FE) model of a below-knee prosthesis of patellar tendon-bearing (PTB) design, and several altered variations of the model have been constructed. A load of approximately 1.5 times normal body weight (984 N) was applied at the heel of the model to simulate heelstrike conditions. The "base" model was then analyzed and revised iteratively until a model which provided consistency between soft tissue elastic modulus and socket displacement was developed. The interface normal and shear stresses obtained from the analysis of this revised base model were highest (about 961, and 463 KPa, respectively) at the distal anterior tip of the socket/stump. Proximally, higher normal stresses (72-78 KPa) were found medially and posteriorly. Proximal shear stresses were highest posteriorly (79 KPa), although shear stresses medially (51 KPa), and laterally (43 KPa), were also much higher than anteriorly (10 KPa). FE analyses were performed on the altered models to determine the relative effects on socket/stump interface stresses of altering the FE model of the prosthesis. Results of the analysis indicate that fabricating the prosthesis from a material with an elastic modulus ten times lower than that of the revised base model can produce reductions in the maximum pressure of up to 14 percent. Large decreases in maximum pressures (71 percent) resulted from the use of a suction socket rather than a conventional socket. Small changes in stump length (2 cm) caused relatively large pressure changes (16 to 18 percent). PMID- 1880747 TI - Equipment and methods for laboratory testing of ankle-foot prostheses as exemplified by the Jaipur foot. AB - A load deflection and a cyclic loading apparatus capable of measuring dorsiflexion/plantarflexion, pronation/supination, internal/external rotation, and cyclic dorsiflexion (60 cycles per minute) of ankle-foot prostheses are described. A test protocol was developed to assess the functional parameters of the Jaipur ankle-foot prosthesis before and after prolonged cyclic loading, with the simultaneous aim of evaluating these machines. The results on 26 Jaipur ankle foot prostheses revealed that: 1) the prosthesis enjoys considerable mobility in three planes, confirming its known versatility; 2) the prosthesis is robust; and, 3) the testing machines deliver reproducible results and are suitable for in house testing of ankle-foot prostheses. PMID- 1880748 TI - Factors influencing rehabilitation of arteriosclerotic lower limb amputees. AB - This survey considered 598 arteriosclerotic amputees over a period of 9 years: 267 below-knee; 81 Gritti-Stokes; 195 above-knee; and 55 double amputees. A walking ability index (WAI) ranging from 1 for a normal gait to 6 for inability to walk was determined for these amputees by clinical grading at 3, 6, 9, and 12 months after prosthesis fitting. Amputees with the below-knee operation had better WAI at 3 and more months than those with either Gritti-Stokes or above knee operations. There was no statistical evidence for a difference between Gritti-Stokes and above-knee operations at any time of assessment of WAI. The 50 59 year-old age group had significantly better WAI at 6, 9, and 12 months than did the 60-69 or 70+ age group, but the 60-69 year-old group was not significantly different from the 70+ age group. On an average, the 78 amputees (14 percent) with ischemic heart disease had a poorer WAI at 6 and more months than did those without it; the 46 amputees (8 percent) with hemiplegia were worse at 12 months than those without hemiplegia; and the 15 amputees (11 percent) with bronchitis were worse at 12 months than those without bronchitis. Double amputees had poorer WAIs at 12 months than those of single amputees. PMID- 1880749 TI - Dynamic characteristics of a sport wheelchair. AB - A single subject performed 36 coast-down trials on a hardwood floor in a sport model wheelchair with velocity ranging from 1.28 to 5.31 m/s (4.6 to 19.1 km/h). A portable computer attached to the wheelchair was used to record the time to the nearest 0.001-second of each half-revolution of a rear wheel. The deceleration during each trial was determined with an average coefficient of variation of 2.6 percent from linear regression of velocity versus time values. A significant relationship (r = 0.97) between deceleration and the square of the velocity was noted in an analysis of the values from the 36 trials. Total drag force and power was calculated as a function of wheelchair velocity from this relationship, indicating that the power output needed to propel the wheelchair increased as a function of the velocity cubed. It is speculated that this noted exponential increase in the energy cost of wheelchair propulsion at higher speeds was due mainly to an increase in air drag. PMID- 1880750 TI - A technique for the determination of center of gravity and rolling resistance for tilt-seat wheelchairs. AB - A balance platform setup was defined for use in the determination of the center of gravity in the sagittal plane for a wheelchair and patient. Using the center of gravity information, measurements from the wheelchair and patient (weight, tire coefficients of friction), and various assumptions (constant speed, level concrete surface, patient-wheelchair system is a rigid body), a method for estimating the rolling resistance for a wheelchair was outlined. The center of gravity and rolling resistance techniques were validated against criterion values (center of gravity error = 1 percent, rolling resistance root mean square error = 0.33 N, rolling resistance Pearson correlation coefficient = 0.995). Consistent results were also obtained from a test dummy and five subjects. Once the center of gravity is known, it is possible to evaluate the stability of a wheelchair (in terms of tipping over) and the interaction between the level of stability and rolling resistance. These quantitative measures are expected to be of use in the setup of wheelchairs with a variable seat angle and variable wheelbase length or when making comparisons between different wheelchairs. PMID- 1880751 TI - Development and testing of artificial low-frequency speech codes. AB - In a new approach to the frequency-lowering of speech, artificial codes were developed for 24 consonants (C) and 15 vowels (V) for two values of lowpass cutoff frequency F (300 and 500 Hz). Each individual phoneme was coded by a unique, nonvarying acoustic signal confined to frequencies less than or equal to F. Stimuli were created through variations in spectral content, amplitude, and duration of tonal complexes or bandpass noise. For example, plosive and fricative sounds were constructed by specifying the duration and relative amplitude of bandpass noise with various center frequencies and bandwidths, while vowels were generated through variations in the spectral shape and duration of a ten-tone harmonic complex. The ability of normal-hearing listeners to identify coded Cs and Vs in fixed-context syllables was compared to their performance on single token sets of natural speech utterances lowpass filtered to equivalent values of F. For a set of 24 consonants in C-/a/ context, asymptotic performance on coded sounds averaged 90 percent correct for F = 500 Hz and 65 percent for F = 300 Hz, compared to 75 percent and 40 percent for lowpass filtered speech. For a set of 15 vowels in /b/-V-/t/ context, asymptotic performance on coded sounds averaged 85 percent correct for F = 500 Hz and 65 percent for F = 300 Hz, compared to 85 percent and 50 percent for lowpass filtered speech. Identification of coded signals for F = 500 Hz was also examined in CV syllables where C was selected at random from the set of 24 Cs and V was selected at random from the set of 15 Vs. Asymptotic performance of roughly 67 percent correct and 71 percent correct was obtained for C and V identification, respectively. These scores are somewhat lower than those obtained in the fixed-context experiments. Finally, results were obtained concerning the effect of token variability on the identification of lowpass filtered speech. These results indicate a systematic decrease in percent correct score as the number of tokens representing each phoneme in the identification tests increased from one to nine. PMID- 1880752 TI - Loneliness and psychological distress. AB - Research on relationships between loneliness and psychological symptoms has generally shown significant positive associations across a wide spectrum of psychopathologies. However, such results may be artificial, to some extent, given the high intercorrelations of typical psychopathology measures. In the current study, we examined associations between psychological symptoms, assessed by the Symptom Check List-90 (SCL-90; Derogatis, Lipman, & Covi, 1973) and loneliness, as measured by the UCLA-R Loneliness Scale (Russell, Peplau, & Cutrona, 1980), in college students. Using partial correlations to control for the confounding influence of generalized distress, relationships between loneliness and individual dimensions of distress were examined. Results indicate a significant association between loneliness and interpersonal sensitivity (low self-esteem) and depression. Other dimensions of distress were not significantly related to loneliness. In addition, no sex differences in patterns of association were observed. Results support the notion that self-blame and self-devaluation are strong correlates of loneliness. PMID- 1880753 TI - Masculinity, femininity, and women scientists' self-esteem and self-acceptance. AB - The literature suggests women scientists are a unique population. The present study investigated differences in self-esteem, self-acceptance, masculinity and femininity among several sample populations of women, including scientists (n = 62), professionals (other than scientists) (n = 89), college students (n = 83), clients (n = 52), and victims of domestic violence (n = 57). The Personal Orientation Inventory (Shostrom, 1974) and Bem Sex Role Inventory (Bem, 1974) were administered to subjects, together with a demographic data sheet. An ANOVA was used to investigate differences between women scientists and other groups of women, and correlations were used to examine the relationship of masculinity and femininity with self-esteem and self-acceptance. Masculinity was found to correlate with self-esteem for all but the student group and with self-acceptance for all but the student and scientist group. Self-acceptance scores were significantly lower for women scientists than for professional and student groups, and femininity scores were significantly lower for scientists than for all other groups of women. PMID- 1880754 TI - The relationship between interaction patterns and agoraphobic fears among college students. AB - In the present study, we investigated the relationships between self-reports of agoraphobic-like anxiety (fear of open, crowded places), panic experiences, childhood separation anxiety, and family interaction patterns in a college student population. The research was conducted in two parts. Correlational analyses of the results of Study 1 revealed significant relationships between anxiety, difficulties in managing life transitions, and measures of family interaction (intergenerational and peer individuation, intergenerational and peer intimacy) as measured by the Personal Authority in the Family System (Questionnaire (Williamson, Bay, Harvey, & Malone, 1985). In Study 2, we observed significant correlations between agoraphobic anxiety and measures of childhood separation anxiety, state and trait anxiety, and patterns of family enmeshment. The results were interpreted in the context of a broad perspective, which includes the role of developmental and interactional variables in the onset and maintenance of agoraphobic anxiety. PMID- 1880755 TI - Delusions and hallucinations of cocaine abusers and paranoid schizophrenics: a comparative study. AB - We compared delusions and hallucinations of 100 cocaine abusers and 100 paranoid schizophrenic subjects admitted to an East Texas state psychiatric hospital. Subjects in both groups feared that individuals or organized groups might harm them in some way, but delusions of the paranoid schizophrenic subjects were more often bizarre than those of the cocaine abuse subjects. "Cocaine bugs" (parasitosis) were more often found in the cocaine abuse subjects. Command hallucinations were found in both groups, but the commands of the schizophrenic group more often related to harming or killing others. Cocaine abusers had a greater frequency of visual hallucinations (47 to 7), distinguished by shadows, flashing lights ("snow lights"), objects moving and bugs crawling on the arm. Finally, the most distinguishing characteristics were identity delusions, possession delusions, grandiose delusions (other than identities and possessions), and delusions that their families were imposters (Capgras Syndrome) reported by paranoid schizophrenics. No such delusions were reported by the cocaine abusers. PMID- 1880756 TI - Psychobiology of the near-miss in fruit machine gambling. AB - Explanations involving the etiology of pathological gambling have tended to emphasize psychosocial factors. However, the possibility that psychobiological factors may be important in the development of pathological gambling behavior should not be ruled out. Psychobiological approaches are becoming ever more prominent with the three main lines of research being (a) a search for a physiological disposition and/or underlying biological substrate in pathological gamblers, (b) an examination of the role of arousal in gambling, and (c) speculation about endorphin-related explanations. The data from questionnaires and interviews with fruit machine gamblers suggest that both physiological and cognitive factors (e.g., the psychology of the near-miss) may be important in the explanation of excessive fruit machine gambling. Thus, if a gambler becomes physiologically aroused when he or she wins or nearly wins, it will stimulate further play, here termed the psychobiology of the near-miss. PMID- 1880757 TI - The axenic cultivation of insect forms of Trypanosoma (Duttonella) vivax and development to the infective metacyclic stage. AB - A method for axenic cultivation of epimastigote and metacyclic forms of Trypanosoma (Duttonella) vivax at 27 degrees C in vitro is described. Iscove's medium was supplemented with specific concentrations of foetal bovine serum, L proline, L-glutamine hypoxanthine, adenosine, pyruvate, and 2-mercaptoethanol. Bloodstream form parasites rapidly transformed into epimastigote forms that grew as surface-adherent colonies in plastic culture flasks. Transformation of epimastigotes to metacyclic forms was first observed 9-12 days after initiation of cultures. Percentages of metacyclics varied: East African T. vivax ranged up to 40% and West African T. vivax ranged up to 24%. Subcultures were made at two week intervals and maintained for several months. Transformation of bloodstream forms to epimastigotes depended on initial attachment to the bottom of culture flasks and the presence of L-proline. The number and maturity of metacyclic forms was influenced by the concentrations of foetal bovine serum, L-proline, L glutamine, and 2-mercaptoethanol. Trypanosomes from cultures were cryopreserved, revived, and used to re-establish fresh axenic cultures. These results represent a significant advance in cultivation of T. vivax insect forms that should enable studies to be accomplished on metabolism, differentiation, and pharmacology of this parasitic protozoan, free from the influence of extraneous cells. PMID- 1880758 TI - The effects of the methylating agent 1,2-bis(methylsulfonyl)-1-methylhydrazine on morphology, DNA content and mitochondrial function of Trypanosoma brucei subspecies. AB - Repeated exposure of trypanosomes in vitro or in vivo to low concentrations of the methylating agent 1,2-bis(methylsulfonyl)-1-methylhydrazine induces a series of moderately synchronous morphological and biochemical changes. Cell division halts and the long-slender bloodstream forms transform to short-stumpy forms via larger intermediate-stage cells which contain approximately double the normal G2 content of DNA. In common with naturally occurring short-stumpy trypanosomes, drug-induced short-stumpy forms do not infect rodents and when transferred to Cunningham's medium, transform to and replicate as procyclics. Furthermore, these short-stumpy forms exhibit alpha-ketoglutarate supported motility and oxygen consumption, acquire the ability to reduce nitroblue tetrazolium (NADH diaphorase positivity) and appear to be in the G1 or G0 stage of the cell cycle based upon DNA content. PMID- 1880759 TI - A serum-free, partly defined medium, PDM-805, for axenic cultivation of Entamoeba histolytica Schaudinn, 1903 and other Entamoeba. AB - We describe the first serum-free, partly defined medium (PDM-805) for cultivating the human enteric pathogen, Entamoeba histolytica, and the reptilian amebae E. barreti, E. invadens, and E. terrapinae. PDM-805 was developed by the stepwise replacement of yeast extract, bovine serum, and a casein peptone digest in TYI-S 33, a medium widely used for the axenic cultivation of these parasites. The defined components include amino acids, carbohydrates, B vitamins, ascorbic acid, tocopherol, thioctic acid, nucleic acid precursors, trace metals, and phosphate buffers. The undefined components include a highly purified bovine serum albumin, a lipoprotein-cholesterol solution from bovine serum, and a dialyzable, autoclavable, water-soluble growth factor(s) having a molecular weight of less than 3,500 prepared from casein peptone. To date, studies on the growth requirements of E. histolytica, strain 200:NIH, show the following are essential for sustained multiplication of this ameba: iron, glucose, biotin, folic acid, niacinamide, pantothenate, pyridoxal, riboflavin, thiamine, cysteine, an ammonium moiety (in addition to that present in cysteine), bovine serum albumin, lipoprotein-cholesterol, and casein peptone dialysate. PMID- 1880760 TI - A test for genetic exchange in mixed infections of Leishmania major in the sand fly Phlebotomus papatasi. AB - We tested if genetic exchange was observable between two strains of Leishmania major (Trypanosomatidae) during mixed infection of the sand fly Phlebotomus papatasi. Previous studies suggested that genetic exchange may occur in natural populations of Leishmania at a low frequency, but experimental crosses examining small numbers of progeny (less than 60) did not reveal hybrid parasites. Accordingly, a strategy was devised to increase the number of progeny that could be screened by 100-fold. Clonal derivatives from two strains that were infective to flies and contained numerous restriction fragment length polymorphisms were characterized and selected for resistance to methotrexate or tunicamycin by gene amplification. A successfully mixed infection of P. papatasi was obtained, and a method was developed for directly plating promastigotes from the gut contents of infected flies onto selective media. Twenty-five hundred independent progeny were scored for the presence of both drug resistance markers. No hybrid parasites were observed, indicating that the frequency of genetic exchange in this cross must be less than 4 x 10(-4). The lines and methods established in this work may prove useful in future studies of the mechanism and frequency of gene exchange in Leishmania. PMID- 1880761 TI - Trypanosoma cruzi: flow cytometric analysis of developmental stage differences in DNA. AB - Flow cytometry and DNA binding-specific fluorescent reagents were used to compare the total DNA, G-C, and A-T content of the epimastigote and trypomastigote stages of Trypanosoma cruzi stocks. Significant total DNA differences of 2-12% between epimastigotes and trypomastigotes were found in three of six stocks studied. The epimastigote G-C content of five of six stocks was 4-8% higher than trypomastigotes, whereas the trypomastigote A-T content was 2.5-13% higher than the epimastigote A-T content. Although no obvious developmental stage association between total DNA and base composition was found, intrastage associations do exist. These observations were unaffected by nucleoprotein extraction implying that the observed differences between trypomastigotes and epimastigotes are not a consequence of nucleoprotein interference with DNA-binding fluorochromes. The nuclei and kinetoplasts of four T. cruzi stocks were isolated and analyzed. Developmental stage differences in nuclear and kinetoplast DNA are stock dependent and base composition-dependent; both organelles contribute to the observed differences in DNA of intact cells. We found a nearly linear association between the percentage of total kinetoplast DNA, G-C, and A-T content. During metacyclogenesis, the G-C content decreases by approximately 7% as epimastigotes transform into metacyclic trypomastigotes. The decrease in G-C content precedes changes in morphology or in complement resistance. If the DNA changes are causally connected to developmental stage transformations in T. cruzi remains to be determined. However, our results could facilitate studies of the molecular genetic processes the parasite uses to successfully complete various phases of its life cycle and, consequently, the disease process it evokes. PMID- 1880762 TI - The putative mitochondrial genome of Plasmodium falciparum. AB - Intraerythrocytic stages of mammalian malarial parasites employ glycolysis for energy production but some aspects of mitochondrial function appear crucial to their survival since inhibitors of mitochondrial protein synthesis and electron transport have antimalarial effects. Investigations of the putative mitochondrial genome of Plasmodium falciparum have detected organellar rRNAs and tRNAs encoded by a 35 kb circular DNA. Some features of the organization and sequence of the rRNA genes are reminiscent of chloroplast DNAs. The 35 kb DNA also encodes open reading frames for proteins normally found in chloroplast but not mitochondrial genomes. An apparently unrelated 6 kb tandemly repeated element which encodes two mitochondrial protein coding genes and fragments of rRNA genes is also found in malarial parasites. The malarial mitochondrial genome thus appears quite unusual. Further investigations are expected to provide insights into the possible functional relationships between these molecules and perhaps their evolutionary history. PMID- 1880763 TI - Copy number control in the Tetrahymena macronuclear genome. PMID- 1880764 TI - Enterocytozoon salmonis n. sp.: an intranuclear microsporidium from salmonid fish. AB - The developmental stages of a recently described microsporidian from the nucleus of hematopoietic cells of salmonid fish were found to be unique among the Microsporida. All observed stages, including meronts, sporonts, and spores were in direct contact with the host cell nucleus (principally hematopoietic cells) of chinook salmon (Oncorhynchus tshawytscha). There is no parasitophorous vacuole and sporogony does not involve formation of a pansporoblastic membrane as with other members of the suborder Apansporoblastina. The extrusion apparatus differentiates prior to division of sporogonial plasmodia. The spores are ovoid (1 x 2 microns) and uninucleate, and possess a coiled polar tube with 8-12 turns. Developmental stages of the salmonid microsporidian are similar to those described for Enterocytozoon bieneusi as found in the intestinal mucosa of human AIDS patients. However, the intranuclear development, different cell types, and host infected clearly separate the salmonid and human parasites. Accordingly, the intranuclear parasite of salmonids is given the name Enterocytozoon salmonis n. sp. within the suborder Apansporoblastina. PMID- 1880765 TI - Real-time examinations of lexical processing in aphasics. AB - We argue that the lesion localizing value of disruptions to modular information processing systems emerges most clearly from on-line analyses of processing. In this respect we seek to show that left anterior (but not left posterior) damage causes slowed information access and we discuss the manner in which this slowing might yield some of the specific syntactic limitations charted in Broca's aphasia. The general possibility we raise is that the cortical area implicated in Broca's aphasia is not necessarily the locus of syntactic representations, but rather sustains particular time-based operating characteristics that in turn sustain normal real-time parsing. PMID- 1880766 TI - [Value of echography in salivary pathology]. AB - Major advances in echography techniques over the past few years include the development of simple high performance units adapted to investigating the salivary glands. This non-traumatic, painless and inexpensive technique offers a means of rapid examination and is fully complementary to X-ray and xero and sialographic imagery, particularly in tumor pathology. The author gives a review of normal images then presents different lesions of the salivary gland. PMID- 1880767 TI - [Tumor of the bone palate in tertiary syphilis. Contribution of x-ray computed tomography]. AB - The authors report the case of two patients presenting with increased bone density and lytic lesions of the skull due to tertiary syphilis. A malignant tumor has late developed on these lesions. Only one patient was imaged with CT Scan which was very useful to determine the tumoral extension. PMID- 1880768 TI - [Current technique of myelography]. AB - Myelography performed with fine needle technique has become virtually innocuous and can be more liberally used in conjunction with CT to produce the CT myelogram, a product of remarkable diagnostic precision. The authors contention is based on a series of 1,357 consecutive myelograms or CT-myelograms recently performed using exclusively 26-gauge spinal needles. PMID- 1880769 TI - [Contribution of scanner in the diagnosis of intestinal infarction]. AB - The clinical expression of arterial mesenteric infarction is not always acute and typical. In venous thrombosis, clinical signs of aggravation occur after a long development. So, clinical pictures of bowel infarction use not be suggestive. For these patients, US performances are sometimes subject to doubt and deceptive. Therefore, CT findings are of the highest importance. In two cases, the authors remind us the CT characterization of vascular and intestinal abnormalities. PMID- 1880770 TI - [Chondrosarcoma of the femur neck simulating a normal variant. A difficult diagnostic pitfall]. AB - We report a case of chondrosarcoma of the femoral neck wrongly considered as a normal variant during a long time due to the initial aspect on the plain films and its location. Precise radiological criteria must allow the differential diagnosis and will be detailed. PMID- 1880771 TI - [X-ray computed tomographic aspects of calcifying metastases. Apropos of 40 cases]. AB - The authors report the results of a study on 40 patients affected by metastases of the calcifying type detected during CT scan imaging for cancer of different origin (colorectum 18 cases, stomach 5, ovary 10, lung 2, bone 2, breast, skin, thyroid 1 case). The sites involved include liver (22), spleen (5), lymph nodes (10), peritoneum (7), diaphragm (2), pleura (2), ovary (1), soft tissue (3), lung (3). Calcification in metastases arises through a double mechanism: primary, with bone formation in osteoid neoplasia (orthoplastic calcification) or ossification of tumour cartilage (metaplastic calcification); secondary as a result of necrosis, hemorrhage and regressive changes (dystrophic and mucoid calcification), particularly after radiation or systemic treatment. Since calcified metastases can strongly mimic granulomatous, parasitic and other neoplastic disease, the clinical history is essential for the diagnosis. PMID- 1880772 TI - [MRI imaging in less than one second: Turbo flash]. PMID- 1880773 TI - [Osteoarticular radiology at the 90 RSNA]. PMID- 1880774 TI - [Report on the Inter-University Specialty Degree in Radiodiagnosis and Medical Imaging of Paris. Evaluation of the first 5 years (1985-1990)]. PMID- 1880775 TI - [Radiology in China]. PMID- 1880776 TI - [AIDS and cranio-encephalic imaging]. PMID- 1880777 TI - [Prevention of allergic complications caused by iodinated opacifying media]. PMID- 1880778 TI - [Venous study of the limbs with duplex Doppler and color Doppler. An iconographic review]. PMID- 1880779 TI - [MRI, geometric distortion of the image and stereotaxy]. AB - The MRI technology may be the starting-point of geometric distorsion. The mathematical preciseness of a spatial location may be disturbed and alter the guidance of an MRI interventionnal act, especially in stereotactic brain biopsy. A review of the literature shows errors of 1 to 1.5 mm. Our results show an error of 0.16 +/- 0.66 mm. The control of quality: homogeneity and calibration of magnetic-field gradients, permit an improve of the balistic preciseness and give permission to realize the guidance of a stereotactic brain biopsy with the alone MRI. PMID- 1880780 TI - [Current technique for the imaging of the face]. AB - In this report, the authors evaluate the indications of the different imaging techniques of the face and the adjacent deep and superficial regions. Thus, CT stays the first examination of the paranasal sinuses completed by MRI especially when an inflammatory pathology is associated with a benign or malignant tumor. Traumatisms of the face must be investigated by CT with an emphasis on the frontal and sagittal reformated sections. The study of the superficial areas of the face (parotid gland) is best explored by US and MRI. MRI gives better results than CT in the exploration of the deep regions of the face. Arteriography remains obligatory in the study of certain tumours specially the nasopharyngeal angiofibroma. PMID- 1880781 TI - [Hemopigmented villonodular synovitis]. AB - Pigmented Villonodular Synovitis (PVNS) in an infrequent tumoral like disease and there are only a few MRI studies published. Concerning our series of five cases compared with the literature, the readers attention is drawn to the etiologies still under debate and to the respective contribution of the different imaging methods. MRI known for its high sensibility, but also for its low specificity in tumoral pathology, has turned out to be, in the case of PVNS, quite remarkable in both regards. The RMI aspect is quite well correlated to the histological structure of this synovial hyperplasia and to its evolution: highly vascular mass at the beginning and then low cellular density stroma, fibrous, with deposition of hemosiderin. In our five cases, as in almost all those previously reported in the literature, MR imaging shows heterogeneous areas of decreased signal intensity on T2 weighted sequences and on two of our cases after administration of gadolinium. Still the same MR aspects can be found in rheumatoid, hemophilic arthritis, as well as synovial chondromatosis, and therefore the clinical background and findings as well as plain films become essential. MR imaging should be the first examination to be undertaken after plain films, leading in most cases to a precise local preoperative assessment. PMID- 1880782 TI - [Clear definitions of chronic bronchopulmonary diseases. Imperative for pneumological practice, teaching and research]. AB - Important divergences in the definition of bronchial asthma, chronic bronchitis and pulmonary emphysema have persisted until the middle 1950's. Definitions were first standardized in 1958 by a group of British experts (CIBA symposium) and made clearer by the WHO Experts Group on Cor Pulmonale in 1961 and by the American Thoracic Society in 1962. The standardized questionnaire proposed by the British Medical Research Council has been widely adopted. For pulmonary emphysema, a precise definition based on anatomical data (dilatation of terminal air spaces with destruction of their walls) has been accepted. Chronic bronchitis is defined in clinical terms (almost daily productive cough 3 months each year, at least on 2 consecutive years; the terms "chronic cough" and "recurrent bronchitis" are still controversial. The greatest difficulties have been encountered in the definition of bronchial asthma; despite a second CIBA symposium (1971) devoted to this problem, it has not been possible to improve on the fairly wide physiological definition put forward in 1958 (bronchial obstruction that varies either spontaneously or under the influence of treatment). For about 15 years peripheral airways obstruction (PAO), sometimes called "small airways disease" has been recognized as a special anatomical and functional syndrome. PMID- 1880783 TI - [Imaging in the diagnosis of vascular complications after hepatic transplantation]. AB - Twenty-nine vascular complications which occurred after 388 hepatic transplantations performed over a 5 year period (14 arterial thromboses, 4 aneurysms and ruptures of the hepatic artery, 8 portal thromboses and 3 peri anastomosis portal stenoses) were investigated retrospectively in order to determine the role of imagery in diagnosing these vascular complications. The best screening examination for the diagnosis of hepatic artery thrombosis appeared to be pulsed Doppler coupled with echography. It provides a means of selecting candidates for arteriography, the only investigation allowing certain diagnosis of thrombosis. False aneurysms, suspected in cases of severe post operative sepsis should be investigated with arteriography even if CAT scans and echo-pulsed Doppler imagery is normal. The diagnosis of portal thrombosis and stenosis relies on echo-pulsed Doppler imagery. In these cases, arteriography is carried out before treatment to evaluate the extent of vascular involvement. Thus echography coupled with pulsed Doppler is the best first intention screening examination to be performed whenever a vascular complication is suspected after hepatic transplantation. Nevertheless, arteriography remains the key examination for the diagnosis and evaluation of these complications. PMID- 1880784 TI - [Cysts of the spleen. Spontaneous involution checked by imaging]. AB - The splenic cysts are rare diseases and the diagnosis is now easier with modern imaging modalities. The authors report two cases of asymptomatic splenic cysts. The spontaneous involution in less than 3 years has been followed by CT Scan. This possible evolution which has never been described, the improvements of the splenic surgery and the risk of serious infectious complications after splenectomy, must modify the indications of the treatment. A US or CT follow up can be purposed for non symptomatic cyst and a partial splenectomy when these lesions are clinically symptomatic. PMID- 1880785 TI - Periportal hepatotoxicity due to allyl alcohol: a myriad of proposed mechanisms. PMID- 1880786 TI - Alteration in de novo pyrimidine biosynthesis during uridine reversal of pyrazofurin-inhibited DNA synthesis. AB - Pyrazofurin, a pyrimidine nucleoside analogue with antineoplastic activity, inhibits cell proliferation and DNA synthesis in cells by inhibiting uridine 5' phosphate (UMP) synthase. It has been previously shown in concanavalin A (con A) stimulated guinea pig lymphocytes (23) that pyrazofurin-inhibited DNA synthesis could be selectively reversed by exogenous uridine (Urd). In this report, we have examined possible mechanisms for the Urd reversal with experiments that determine the ability of exogenous Urd to (a) interfere with either the intracellular transport of pyrazofurin, or the conversion of pyrazofurin to its intracellularly active form, pyrazofurin-5'-phosphate; (b) reverse the pyrazofurin block of [14C]orotic acid incorporation into DNA; and (c) alter the pattern of exogenous [3H]Urd incorporation into DNA-thymine (DNA-Thy) and DNA-cytosine (DNA-Cyt) during pyrazofurin inhibition of pyrimidine de novo biosynthesis. The results of these experiments showed that Urd reversal does not occur through altered pyrazofurin transport or intracellular conversion to pyrazofurin-5'-phosphate, nor does it alter the distribution of [3H]Urd in DNA-Thy and DNA-Cyt. Instead, these findings indicate that the primary mechanism for exogenous Urd reversal of pyrazofurin inhibition of DNA synthesis involves the reversal of pyrazofurin inhibition of UMP synthase, thus restoring orotic acid incorporation into lymphocyte DNA through the pyrimidine de novo pathway. PMID- 1880787 TI - Interaction of benzanthrone with cytochrome P450: altered patterns of hepatic xenobiotic metabolism in rats. AB - Benzanthrone, an anthraquinone dye intermediate, is commonly used for the synthesis of a number of polycyclic vat and disperse dyes. Our prior studies have shown that benzanthrone can be metabolized by rat hepatic microsomal cytochrome P450 (P450) (Biochem. Int., 18, 1989, 1237). In this study, the interaction of benzanthrone with rat hepatic microsomal P-450 and its effect on xenobiotic metabolism have been investigated. Parenteral administration of benzanthrone (40 mg/kg body weight) for 3, 7, or 21 days caused no change in the relative body weight or organ weight of rats. The levels of P450 were found to be reduced (33% 50%) in all the benzanthrone-exposed animals at all the time periods. In vitro addition of benzanthrone caused a spectral change with oxidized P450 and concentration-dependent reduction in the carbon monoxide spectrum of dithionite reduced P450. The addition of benzanthrone to hepatic microsomes prepared from phenobarbital-treated rats resulted in spectral changes characterized by an absorbance maximum at 397 nm indicative of type I binding. In vitro addition of benzanthrone showed a concentration-dependent inhibition of hepatic aminopyrine N demethylase (APD) and ethoxyresorufin-O-deethylase (ERD) activities with respective I50 values of 9.5 x 10(-4) and 8.0 x 10(-5) M. However, the inhibition of aryl hydrocarbon hydroxylase (AHH) even at the highest concentration of benzanthrone (10(-2) M), was of the order of only 29%. In vivo administration of benzanthrone also led to the inhibition of APD, AHH, and ERD activities at all treatment times although the magnitude of inhibition was of a lower order.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880788 TI - Sublethal effects of pentachlorophenol in the abalone (Haliotis rufescens) as measured by in vivo 31P NMR spectroscopy. AB - The sublethal biochemical effects of pentachlorophenol (PCP) were investigated in live, intact red abalones (Haliotis rufescens), using a flow-through exposure system, by in vivo 31P NMR spectroscopy. Based on rangefinding tests (6-hr LC50 = 1.6 mg/L; 6-hr no-observable-effect-level (NOEL) = 0.8 mg/L), three abalones were separately exposed to a sublethal concentration (1.2 mg/L) for 5 hr, followed by a 13 hr recovery period. Effects in foot muscle included both a decrease in phosphoarginine and an increase in inorganic monophosphate concentrations ([PA] and [Pi], respectively); both foot muscle concentrations of adenosine triphosphate [ATP] and intracellular pH (pHi) also declined. Parallel in vitro experiments revealed that concentrations of glycerol 3-phosphate, lactate, citrate, succinate, malate, and alanine (Ala) all increased, while those of glyceraldehyde 3-phosphate and glutamine (Gln) remained stable. Also, these effects were not evident until 2 hr into exposure, possibly the time required for PCP to attain an effective concentration in foot muscle. During recovery, while Pi declined to pre-exposure levels, [PA] completely recovered in only one individual. Also, realkalinization of pHi was similar to recovery of [Pi], and ATP returned to near-initial levels, as did glycerol 3-phosphate, lactate, succinate, malate, and Ala; glyceraldehyde 3-phosphate, citrate, and Gln levels declined. Recovery responses corresponded to the time for PCP clearance from foot muscle. The effects of PCP were similar to those of hypoxia, fatigue, hypersalinity, and arginine kinase inhibitors, and so sublethal PCP concentrations may also inhibit electron transport and arginine kinase as well as uncouple mitochondrial oxidative phosphorylation in intact molluscs. Thus, the effects of pollutants on key biochemical processes may now be measured in intact aquatic organisms as they occur, improving our ability to accurately assess the environmental effects of pollutants in the laboratory. PMID- 1880789 TI - Molecular structure, polymorphism, and toxicity of lantadene A, the pentacyclic triterpenoid from the hepatotoxic plant Lantana camara. AB - Lantadene A (22 beta-angeloyloxy-3-oxo-olean-12-en-28-oic acid), a pentacyclic triterpenoid compound from lantana (Lantana camara) leaves has been obtained in two polymorphic forms I and II. Form I had white, fluffy, and rod-shaped uniform crystals. Form II particles were irregular, shining, and polyhedral. The two forms differed in melting behavior. The powder x-ray diffraction of form I showed sharp peaks whereas from II did not contain distinct peaks. From single-crystal three-dimensional x-ray structure determination, the molecular structure of form I has been established. A/B and B/C rings of the molecule are trans fused while D/E rings are cis fused. The packing of the molecule is stabilized by hydrogen bonding. Form I of lantadene A was non-toxic to guinea pigs on oral administration. Form II induced ictericity and toxicity associated with decrease in feed intake and fecal output, hepatomegaly, increase in plasma bilirubin, and acid phosphatase activity. PMID- 1880790 TI - Localization of the sulfur-cyanolysis site of serum albumin to subdomain 3-AB. AB - The results of kinetic experiments measuring the effects of a variety of ligands on the sulfur-cyanolysis reaction catalyzed by serum albumin point to the conclusion that the active site for cyanolysis is on subdomain 3-AB. Relationships among the inhibition by short-chain fatty acids, the activation by p-nitrophenyl acetate, and the influence of bilirubin and L-tryptophan on these effects indicate that the cyanolysis active site and the known primary binding site for indoles are both near, but on opposite sides of, tyrosine-409 of bovine albumin (tyrosine-411 of human albumin). PMID- 1880791 TI - A negative slope in the current-voltage relationship of the Na+/K+ pump in Xenopus oocytes produced by reduction of external [K+]. AB - To investigate the voltage dependence of the Na+/K+ pump, current-voltage relations were determined in prophase-arrested oocytes of Xenopus laevis. All solutions contained 5 mM Ba2+ and 20 mM tetraethylammonium (TEA) to block K+ channels. If, in addition, the Na+/K+ pump is blocked by ouabain, K(+)-sensitive currents no larger than 50 nA/cm2 remain. Reductions in steady-state current (on the order of 700 nA/cm2) produced by 50 microM ouabain or dihydro-ouabain or by K+ removal, therefore, primarily represent current generated by the Na+/K+ pump. In Na(+)-free solution containing 5 mM K+, Na+/K+ pump current is relatively voltage independent over the potential range from -160 to +40 mV. If external [K+] is reduced below 0.5 mM, negative slopes are observed over this entire voltage range. Similar results are seen in Na(+)- and Ca(2+)-free solutions in the presence of 2 mM Ni2+, an experimental condition designed to prevent Na+/Ca2+ exchange. The occurrence of a negative slope can be explained by the voltage dependence of the apparent affinity for activation of the Na+/K+ pump by external K+, consistent with the existence of an external ion well for K+ binding. In 90 mM Na+, 5 mM K+ solution, Na+/K+ pump current-voltage curves at negative membrane potentials have a positive slope and can be described by a monotonically increasing sigmoidal function. At an extracellular [K+] of 1.3 mM, a negative slope was observed at positive potentials. These findings suggest that in addition to a voltage-dependent step associated with Na+ translocation, a second voltage-dependent step that is dependent on external [K+], possibly external K+ binding, participates in the overall reaction mechanism of the Na+/K+ pump. PMID- 1880792 TI - Assessing adaptive and maladaptive coping in the early phase of acute myocardial infarction. AB - We assessed retrospectively symptom management behaviors among 45 patients with acute myocardial infarction (AMI). Cluster analysis was conducted on data from the Structured Interview (SI), in order to group patients according to the global TABP, Anger-In, Potential for Hostility, and a newly derived measure of Behavioral Compensation for Stress (BEH-COMP). Two groups were identified. MALADAPT SI-copers (N = 24) had higher scores on Anger-In and Hostility and lower scores on BEH-COMP in comparison to the ADAPT SI-copers (N = 21), while no difference was observed on TABP. The SI groups were next compared on AMI symptom management behaviors. A hierarchical discriminant analysis found that the MALADAPT group reported greater distraction from AMI symptoms, were relief seeking behavior, and greater perceived vulnerability to reinfarction. AMI coping behaviors correlated meaningfully with delay in seeking medical assistance. Further research is warranted, given the potential for using the ADAPT/MALADAPT SI-profiles to predict adjustment to AMI. PMID- 1880793 TI - The factor structure and cross-sectional distributional properties of the Beth Israel/UCLA Functional Status Questionnaire. AB - The functional status of ambulatory patients is an important correlate of their emotional and physical well-being and is subject to influence by the delivery of health care. First, the present study obtains a profile on the FSQ for a large sample of young, healthy adults (N = 508 college undergraduates), for use as an "empirical standard" against which to evaluate the effect of disease or injury on an individual's functional status. Second, cross-sectional analyses contrast distributional features of responses to the FSQ between (a) the present younger, healthy sample and (b) a previously published, older ambulatory patient sample. These analyses suggest that the FSQ has acceptable discriminant validity for intergroup comparisons. Finally, confirmatory structural analyses suggest that the theoretical six-factor model hypothesized to underlie responses to the FSQ has a modest, yet acceptable, goodness of fit to actual data. PMID- 1880794 TI - The Pain Behavior Check List (PBCL): factor structure and psychometric properties. AB - The construct of "pain behaviors" as observable and measurable manifestations of pain occupies a central role in Fordyce's operant model of pain. The present study was designed to evaluate the multidimensional nature of the construct and to explore the psychometric properties of a newly developed self-report instrument called the Pain Behavior Check List (PBCL). Subjects were 126 chronic pain patients who completed an initial version of the PBCL and other standardized questionnaires as part of their evaluation by the West Haven VAMC. Factor analysis identified four factors labeled Distorted Ambulation, Affective Distress, Facial/Audible Expressions, and Seeking Help. Substantial reliability and stability estimates for the total PBCL and the subscales support the potential clinical and theoretical utility of the instrument. PMID- 1880795 TI - Control over uplifts and hassles and its relationship to adaptational outcomes. AB - The relationship of perceived control over daily uplifts and hassles to depression and restraint was examined in a sample of 140 middle-class sixth graders. Results indicated that greater control over uplifts was associated with better functioning and lower control over hassles with poorer functioning, even after partialing out the respective number of uplifts and hassles reported. Moreover, when directly compared, control over uplifts showed more powerful associations with adaptational outcomes than did control over hassles. In a separate analysis, the number of uplifts over which children reported high control showed opposite relationships to adaptational outcomes than did the number of uplifts over which children reported low control. A different pattern appeared for hassles. Although the number of hassles with low control was associated with poorer functioning, the number of hassles over which children had high control was unrelated to adaptational outcomes. The possibility that control operates somewhat differently for positive and negative events is discussed. PMID- 1880796 TI - Tryptophan and high-carbohydrate diets as adjuncts to smoking cessation therapy. AB - Treatments that reduce the immediate effects of smoking withdrawal have potential for helping smokers quit. Serotonin-enhancing substances, such as tryptophan and high-carbohydrate diets, have been used in clinical disorders to relieve negative affect, a classic symptom of cigarette withdrawal. This research project investigated the use of tryptophan (50 mg/kg/day) and high-carbohydrate diets, together with more traditional smoking cessation treatment techniques, to ameliorate the smoking withdrawal syndrome and to improve abstinence rates. Subjects were randomly assigned to receive either tryptophan (n = 16) or placebo (n = 15). Standard smoking cessation treatment was identical for the experimental and control groups and consisted of four 2-hr weekly sessions of multicomponent group therapy. Smoking behavior, symptoms of nicotine withdrawal, and negative affect were assessed during a 2-week withdrawal period. Tryptophan-treated subjects who could not fully abstain were able to smoke fewer daily cigarettes. Reported anxiety and other withdrawal symptoms were lower in the tryptophan group compared with control subjects. These data suggest that serotonin-enhancing substances show promise for use as an adjunct to existing smoking cessation programs. PMID- 1880797 TI - Ionic interactions with parvalbumins. Crystal structure determination of pike 4.10 parvalbumin in four different ionic environments. AB - The crystal structure of the Ca-loaded form of pike 4.10 parvalbumin (minor component from pike muscle belonging to the beta phylogenetic series), with both its primary sites CD and EF occupied by Ca2+ ions and its third site occupied by an ammonium ion, as previously determined at 1.93 A resolution, has now been refined to a resolution of 1.65 A. The crystallization of this parvalbumin in different ionic environments has allowed three novel non-isomorphous crystalline forms to be obtained: (1) a first form, crystallized in the presence of a mixture of ammonium sulphate and manganese sulphate, for which all the cation binding sites in the protein are occupied by Mn2+; (2) a second form crystallized in the presence of MgSO4 as the precipitating agent, only differs from the Ca/NH4 form by the occupation of the third site by Mg2+, whereas the primary sites remain occupied by Ca2+; (3) a third form, also crystallized in the presence of MgSO4, corresponds to a well-defined molecular species with both the primary EF site and the third site occupied by Mg2+, whereas the primary CD site remains occupied by CA2+. The corresponding molecular structures reported here have been determined at resolutions between 1.8 and 2.4 A. The comparison of the different crystal structures allows the structural modifications accompanying the substitution of the primary sites by cations differing significantly in their ionic radii (Ca2+, Mn2+, Mg2+) to be investigated in detail, and it also leads to a precise description of the third site in a typical beta parvalbumin. The substitution Ca2+ by Mg2+ within the primary site EF is characterized by a "contraction" of the co-ordination sphere, with a decrease of the mean oxygen-metal distance by a value of 0.25 A and a decrease of the co-ordination number from 7 to 6, as a consequence of the loss of a bidentate ligand (Glu101), which becomes a monodentate one. Such an adaptation of the co-ordination sphere around a cation of smaller size involves, among others, the transformation of the Glu101 side chain from the stable gauche(+) form to the less stable gauche(-) form. The third site is clearly described as a satellite of the CD primary site, since both sites possess common protein ligands, such as Asp53 and Glu59. Furthermore, Asp61 appears as a specific ligand of the third site in the different environments investigated in this work. We finally discuss the relevance of the third site to parvalbumin phylogeny. PMID- 1880798 TI - Effect of single amino acid replacements on the thermodynamics of the reactive site peptide bond hydrolysis in ovomucoid third domain. AB - We have measured equilibrium constants, Khyd, at pN 6 for the hydrolysis of the reactive site peptide bond (bond between residues 18 and 19) in 42 sequenced variants (39 natural, 3 semisynthetic) of avian ovomucoid third domains. The values range from 0.4 to approximately 35. In 35 cases the effect of a single amino acid replacement on Khyd could be calculated, 13 are without effect and 22 range from a factor of 1.25 to 5.5. Several, but not all, of the effects can be rationalized in terms of residue-residue interactions that are affected by the reactive site hydrolysis. As the measurements are very precise it appears that additional measurements on designed rather than natural variants should allow for the precise measurement of side-chain--side-chain interaction energies. PMID- 1880799 TI - Multiple display of foreign peptides on a filamentous bacteriophage. Peptides from Plasmodium falciparum circumsporozoite protein as antigens. AB - We describe here two systems for encoding foreign amino acid sequences in the exposed N-terminal segment of the major coat protein of bacteriophage fd. Small peptides can be encoded directly; larger peptides are encoded in hybrid bacteriophage particles, in which the capsid is formed from a mixture of wild type and modified coat proteins. In both cases, the peptides are present in multiple copies per phage particle. Peptides that represent the circumsporozoite protein, the major surface antigen of the sporozoites of the malaria parasite, Plasmodium falciparum, were inserted in this way and found to be highly immunogenic. These systems should prove to be valuable in displaying specific or random peptides as antigens, and could lead to cheap and effective vaccines. They will also allow rapid screening of peptides as potential agents of other biological effects, with important applications in biomolecular design. PMID- 1880800 TI - Unidirectional replication as visualized by two-dimensional agarose gel electrophoresis. AB - Two-dimensional (2D) agarose gel electrophoresis is progressively replacing electron microscopy as the technique of choice to map the initiation and termination sites for DNA replication. Two different versions were originally developed to analyze the replication of the yeast 2 microns plasmid. Neutral/Neutral (N/N) 2D agarose gel electrophoresis has subsequently been used to study the replication of other eukaryotic plasmids, viruses and chromosomal DNAs. In some cases, however, the results do not conform to the expected 2D gel patterns. In order to better understand this technique, we employed it to study the replication of the colE1-like plasmid, pBR322. This was the first time replicative intermediates from a unidirectionally replicated plasmid have been analyzed by means of N/N 2D agarose gel electrophoresis. The patterns obtained were significantly different from those obtained in the case of bidirectional replication. We showed that identification of a complete are corresponding to molecules containing an internal bubble is not sufficient to distinguish a symmetrically located bidirectional origin from an asymmetrically located unidirectional origin. We also showed that unidirectionally replicated fragments containing a stalled fork can produce a pattern with an inflection point. Finally, replication appeared to initiate at only some of the potential origins in each multimer of pBR322 DNA. PMID- 1880801 TI - Structure and evolution of the cytotoxic cell proteinase genes CCP3, CCP4 and CCP5. AB - A family of serine proteinases is believed to be important in cell-mediated cytotoxicity. Presented here are the genomic sequences for three murine members of this cytotoxic cell proteinase (CCP) family: the CCP3, CCP4 and CCP5 genes. All three of these genes have introns inserted at the same codon sites and the same exon distribution of the active site residues. These characteristics are also shared with the CCP1 and CCP2 genes, the charter members of the CCP gene family. Phylogenetic analysis using intron and exon sequences suggests that all five genes arose by various duplication events. This analysis also indicates that the recently described HuCCPX and CCP2 genes originated from recombination events between genes of different lineages. A phylogenetic and Southern analysis of the recombinant HuCCPX gene suggests that the human genome contains an additional CCP gene that has yet to be described. Finally, evidence is presented suggesting that the cDNA clone originally describing the CCP5 gene was derived from an alternately spliced transcript. PMID- 1880802 TI - A new family of powerful multivariate statistical sequence analysis techniques. AB - A novel multivariate statistical approach is presented for extracting and exploiting intrinsic information present in our ever-growing sequence data banks. The information extraction from the sequences avoids the pitfalls of intersequence alignment by analyzing secondary invariant functions derived from the sequences in the data bank rather than the sequences themselves. Such typical invariant function is a 20 x 20 histogram of occurrences of amino acid pairs in a given sequence or fragment thereof. To illustrate the potential of the approach an analysis of 10,000 protein sequences from the National Biomedical Research Foundation Protein Identification Resource is presented, whose analysis already reveals great biological detail. For example, zeta-hemoglobin is found to lie close to amphibian and fish chi-hemoglobin which, in turn, is an important clue to the physiological function of this mammalian early embryonic hemoglobin. The multivariate statistical framework presented unifies such apparently unrelated issues as phylogenetic comparisons between a set of sequences and distance matrices between the constituents of the biological sequences. The Multivariate Statistical Sequence Analysis (MSSA) principles can be used for a wide spectrum of sequence analysis problems such as: assignment of family memberships to new sequences, validation of new incoming sequences to be entered into the database, prediction of structure from sequence, discrimination of coding from non-coding DNA regions, and automatic generation of an atlas of protein or DNA sequences. The MSSA techniques represent a self-contained approach to learning continuously and automatically from the growing stream of new sequences. The MSSA approach is particularly likely to play a significant role in major sequencing efforts such as the human genome project. PMID- 1880803 TI - Mutational analysis of the RNA pseudoknot component of a coronavirus ribosomal frameshifting signal. AB - The genomic RNA of the coronavirus IBV contains an efficient ribosomal frameshift signal at the junction of the overlapping 1a and 1b open reading frames. The signal is comprised of two elements, a heptanucleotide "slip-site" and a downstream tertiary RNA structure in the form of an RNA pseudoknot. We have investigated the structure of the pseudoknot and its contribution to the frameshift process by analysing the frameshifting properties of a series of pseudoknot mutants. Our results show that the pseudoknot structure closely resembles that which can be predicted from current building rules, although base pair formation at the region where the two pseudoknot stems are thought to stack co-axially is not a pre-requisite for efficient frameshifting. The stems, however, must be in close proximity to generate a functional structure. In general, the removal of a single base-pair contact in either stem is sufficient to reduce or abolish frameshifting. No primary sequence determinants in the stems or loops appear to be involved in the frameshift process; as long as the overall structure is maintained, frameshifting is highly efficient. Thus, small insertions into the pseudoknot loops and a deletion in loop 2 that reduced its length to the predicted functional minimum did not influence frameshifting. However, a large insertion (467 nucleotides) into loop 2 abolished frameshifting. A simple stem-loop structure with a base-paired stem of the same length and nucleotide composition as the stacked stems of the pseudoknot could not functionally replace the pseudoknot, suggesting that some particular conformational feature of the pseudoknot determines its ability to promote frameshifting. PMID- 1880804 TI - Organization and function of binding sites for the transcriptional activator NifA in the Klebsiella pneumoniae nifE and nifU promoters. AB - The interaction of the Klebsiella pneumoniae NifA protein, a sigma 54-dependent activator, with the nifE and nifU promoters was analysed. At these promoters NifA established contacts in addition to those predicted by the minimal formulation NifA binding site (5'-TGT-N10-ACA). The positions of the contacts indicate that bound NifA molecules could assemble to form an oligomer. At both promoters contacts with NifA are made predominantly on one face of the DNA helix, and all contacts appear necessary for full activation by NifA. The close contacts made by NifA appear to be made by the DNA-binding domain of NifA. This domain shows specific DNA-binding activity in vitro. The binding of NifA to one site in the nifU promoter depends upon occupancy of additional upstream sequences by NifA. At the nifE promoter NifA binds adjacent to an integration host factor (IHF) binding site, but in contrast to results obtained with the nifU promoter IHF does not diminish nifE promoter occupancy by NifA. The IHF requirement for efficient in vivo activation of the nifU promoter by NifA was greater than that of the nifE promoter. Accordingly, the affinity of IHF for the nifU promoter is higher than for the nifE promoter. Amongst promoters utilizing the sigma 54 holoenzyme, the nifE promoter appears somewhat atypical in having the activator bound at around position -74 rather than the usual 100 base-pairs or more upstream from the transcription start site. PMID- 1880805 TI - Mutational specificity of DNA precursor pool imbalances in yeast arising from deoxycytidylate deaminase deficiency or treatment with thymidylate. AB - Disruption of the dCMP deaminase (DCD1) gene, or provision of excess dTMP to a nucleotide-permeable strain, produced dramatic increases in the dCTP or dTTP pools, respectively, in growing cells of the yeast Saccharomyces cerevisiae. The mutation rate of the SUP4-o gene was enhanced 2-fold by the dCTP imbalance and 104-fold by the dTTP imbalance. 407 SUP4-o mutations that arose under these conditions, and 334 spontaneous mutations recovered in an isogenic strain having balanced DNA precursor levels, were characterized by DNA sequencing and the resulting mutational spectra were compared. Significantly more (greater than 98%) of the changes resulting from nucleotide pool imbalance were single base-pair events, the majority of which could have been due to misinsertion of the nucleotides present in excess. Unexpectedly, expanding the dCTP pool did not increase the fraction of A.T----G.C transitions relative to the spontaneous value nor did enlarging the dTTP pool enhance the proportion of G.C----A.T transitions. Instead, the elevated levels of dCTP or dTTP were associated primarily with increases in the fractions of G.C----C.G or A.T----T.A. transversions, respectively. Furthermore, T----C, and possibly A----C, events occurred preferentially in the dcd1 strain at sites where dCTP was to be inserted next. C- --T and A----T events were induced most often by dTMP treatment at sites where the next correct nucleotide was dTTP or dGTP (dGTP levels were also elevated by dTMP treatment). Finally, misinsertion of dCTP or dTTP did not exhibit a strand bias. Collectively, our data suggest that increased levels of dCTP and dTTP induced mutations in yeast via nucleotide misinsertion and inhibition of proofreading but indicate that other factors must also be involved. We consider several possibilities, including potential roles for the regulation and specificity of proofreading and for mismatch correction. PMID- 1880806 TI - Regulation of smooth muscle myosin light chain kinase. Allosteric effects and co operative activation by calmodulin. AB - The activation of smooth muscle myosin light chain kinase (MLCKase) by calcium and calmodulin (CM) was investigated over a wide range of concentrations of the enzyme using myosin (MY) or its isolated phosphorylatable light chain (L20) as substrates. The enzyme showed allosteric behavior. The specific phosphorylation activity was dependent on the concentration of MLCKase as well as on the concentrations of both substrates. However, at the lower (nanomolar) range of kinase the corresponding substrate rate relationships were hyperbolic. A high positive level of co-operativity of kinase was also observed for activation by CM in the presence of Ca2+. There was a pronounced CM/Ca-dependent inhibition of MLCKase activity when its molar ratio to CM was four to one or more. These kinetic data suggested that MLCKase could exist in several oligomeric forms, with an inactive high molecular size form and an active low molecular size form (protomers and/or dimers). This conclusion was confirmed by gel filtration studies. CM was not directly involved in the oligomerization process but instead, the oligomeric kinase shared an increased affinity for CM. PMID- 1880807 TI - Refined crystal structure of lipoamide dehydrogenase from Azotobacter vinelandii at 2.2 A resolution. A comparison with the structure of glutathione reductase. AB - The structure of lipoamide dehydrogenase from Azotobacter vinelandii has been refined by the molecular dynamics technique to an R-factor of 19.8% at 2.2 A resolution. In the final model, the root-mean-square deviation from ideality is 0.02 A for bond lengths and 3.2 degrees for bond angles. The asymmetric unit comprises two subunits, each consisting of 466 amino acid residues and the prosthetic group FAD, plus 512 solvent molecules. The last ten amino acid residues of both chains are not visible in the electron density distribution and they are probably disordered. The operation required to superimpose the two chains forming the dimer is a rotation of exactly 180 degrees with no translation component. The final model shows the two independently refined subunits to be very similar, except for six loops located at the surface of the molecule. The structure of each subunit of the enzyme consists of four domains with the catalytic centre located at the subunit interface. The reactive disulphide bridge, 48-53, is oxidized with S gamma of Cys53 located 3.5 A away from carbon C 4a of the isoalloxazine ring. The side-chain of His450' points its N epsilon 2 towards S gamma of Cys48 and is hydrogen bonded to the carboxylate of Glu455'. The FAD is bound in an extended conformation and the isoalloxazine ring is not completely planar with an angle between the pteridine and the benzene ring of 7.3 degrees in the first subunit and of 12.1 degrees in the second one. The overall folding of lipoamide dehydrogenase is very similar to that of glutathione reductase. However, a comparison of the two enzymes, which have only 26% sequence identity, reveals significant conformational differences. These concern the tertiary as well as the quaternary structure of the two molecules. In each subunit of lipoamide dehydrogenase the NAD-binding domain and the interface domain appear to be differently oriented with respect to the FAD-binding domain by 7.1 degrees and 7.8 degrees, respectively. The interface domain contains, in addition, major changes in tertiary structure. Furthermore, the two subunits forming the dimer appear to be shifted with respect to each other by more than 4 A, when the lipoamide dehydrogenase dimer is compared with that of glutathione reductase. In spite of all these changes at the tertiary and quaternary level the active sites of the enzymes, which occur at the dimer interface, appear to be remarkably similar.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1880808 TI - Refined 1.83 A structure of trypanosomal triosephosphate isomerase crystallized in the presence of 2.4 M-ammonium sulphate. A comparison with the structure of the trypanosomal triosephosphate isomerase-glycerol-3-phosphate complex. AB - Triosephosphate isomerase (TIM) is a dimeric glycolytic enzyme. TIM from Trypanosoma brucei brucei has been crystallized at pH 7.0 in 2.4 M-ammonium sulphate. The well-diffracting crystals have one dimer per asymmetric unit. The structure has been refined at 1.83 A resolution with an R-factor of 18.3% for all data between 6 A and 1.83 A (37,568 reflections). The model consists of 3778 protein atoms and 297 solvent atoms. Subunit 1 is involved in considerably more crystal contacts than subunit 2. Correlated with these differences in crystal packing is the observation that only in the active site of subunit 2 is a sulphate ion bound. Furthermore, significant differences with respect to structure and flexibility are observed in three loops near the active site. In particular, there is a 7 A positional difference of the tip of the flexible loop (loop 6) when comparing subunit 1 and subunit 2. Also, the neighbouring loops (loop 5 and loop 7) have significantly different conformations and flexibility. In subunit 1, loop 6 is in an "open" conformation, in subunit 2, loop 6 is in an "almost closed" conformation. Only in the presence of a phosphate-containing ligand, such as glycerol-3-phosphate, does loop 6 take up the "closed" conformation. Loop 6 and loop 7 (and also to some extent loop 5) are rather flexible in the almost closed conformation, but well defined in the open and closed conformations. The closing of loop 6 (167 to 180), as observed in the almost closed conformation, slightly changes the main-chain conformation of the catalytic glutamate, Glu167, leading to a change of the chi 1 angle of this residue from approximately -60 degrees to approximately 60 degrees and the weakening of the hydrogen bonds between its polar side-chain atoms and Ser96. In the closed conformation, in the presence of glycerol-3-phosphate, the main-chain atoms of Glu167 remain in the same position as in the almost closed conformation, but the side-chain has rotated around the CA-CB bond changing chi 1 from approximately 60 degrees to approximately -60 degrees. In this new position the hydrogen bonding to Ser96 is completely lost and also a water-mediated salt bridge between OE2(Glu167) and NE(Arg99) is lost. Comparison of the two independently refined subunits, showed that the root-mean-square deviation for all 249 CA atoms is 0.9 A; for the CA atoms of the beta-strands this is only 0.2 A. The average B-factor for all subunit 1 and subunit 2 atoms is 20 A2 and 25 A2, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1880809 TI - Magnesium inhibits the responses to neuropeptide Y in the rabbit coronary artery. AB - Neuropeptide Y (NPY) has been shown to cause direct vasoconstriction of coronary arteries in many species, including dogs, rabbits and man, which is selectively inhibited by calcium-channel blocking agents. Recently, NPY has also been reported to inhibit the relaxation to noradrenaline in isolated rabbit coronary arteries, but the composition of the Krebs solution described in this study indicated that it contained no magnesium. Since magnesium is known to be a physiological antagonist of calcium and to have a profound influence on the contraction of coronary vascular smooth muscle, we examined the importance of magnesium in modulating both the direct vasoconstrictor response to NPY and the NPY-induced inhibition of relaxation to noradrenaline, using ring preparations of rabbit circumflex coronary artery. PMID- 1880810 TI - Isolation of rat cardiac sarcoplasmic reticulum with improved Ca2+ uptake and ryanodine binding. AB - The instability of the oxalate-supported Ca2+ uptake activity of rat cardiac sarcoplasmic reticulum (CSR) in ventricular homogenates most likely accounts for the low specific activity of the rate of oxalate-supported Ca2+ uptake in previously reported fractions of isolated rat CSR. We have found that CSR vesicles with improved Ca2+ transport capabilities can be isolated if 1 M KCl is used to stabilize the CSR activity and to allow the extraction of the CSR from the cellular debris. The average rate of Ca2+ uptake by the isolated rat CSR in the presence of 10 mM oxalate at 37 degrees C was 0.45 mumols/min-mg in the absence of CSR Ca2+ channel blockers and 0.87 mumols/min-mg in the presence of 10 microM ruthenium red. The Ca(2+)-dependent ATPase activity under the conditions of oxlate-supported uptake was 1.25 mumols/min-mg and 0.84 mumols/min-mg in the absence and presence of 10 microM ruthenium red, respectively. The rat CSR vesicles bound 3H-ryanodine with a Kd of 1.45 nM and a Bmax of 3.7 pmol mg. The level of phosphorylated intermediate was 0.30 nmol/mg. The values Bmax, EP and Ca(2+)-ATPase activity are from one-third to one-half of those previously reported for isolated canine CSR vesicles. These results suggest that the isolated rat CSR may be quite similar to dog CSR. PMID- 1880811 TI - Single-channel recording of inwardly rectifying potassium currents in developing myocardium. AB - Properties of the inwardly rectifying K+ channel, which contributes to the maintenance of the resting membrane potential, were studied in neonatal rabbit ventricular myocytes using the patch-clamp technique. Inward rectification was evident in single-channel current-voltage (I-V) relations at potentials positive to the potassium equilibrium potential (Ek = 0 mV with [K+]o = [K+]i = 150 mM, [Mg2+]i = 2 mM). The single-channel conductance was 3.2 +/- 0.1 pS in physiological (5.4 mM) [K+]o. The zero-current potential shifted 48.4 +/- 2.4 mV for a ten-fold change in [K+]o in neonatal cells. External Ba2+ blocked the current in a dose-dependent manner. The voltage dependence, open-state probability and channel density of this channel were compared between neonatal and adult ventricular myocytes isolated by similar techniques. The open-state probability of the channel was approximately the same in neonatal (0.39 +/- 0.06, n = 13) as in adult cells (0.4 +/- 0.05, n = 11). However, in symmetrical transmembrane K+ concentration [( K+]o = [K+]i = 150 mM), the single channel conductance was significantly smaller in neonatal (25 +/- 0.3 pS, n = 25) as compared with adult cells (31 +/- 0.4 pS, n = 12). In addition, the relationship between resting membrane potential and [K+]o was measured in neonatal and adult myocytes. The resting membrane potential in the neonate was less dependent on [K+]o than in the adult. These results are consistent with an age-related change in resting membrane K+ permeability which may result from a developmental change in the single-channel conductance properties of the inwardly rectifying K+ channel. PMID- 1880812 TI - Calcium antagonists and cardiac noradrenaline release in ischemia. AB - The effects of the calcium antagonists verapamil, gallopamil, nifedipine, felodipine and diltiazem on noradrenaline release during ischemia were studied in isolated perfused rat hearts. Endogenous levels of noradrenaline and its intraneuronal metabolite dihydroxyphenylethyleneglycol (DOPEG) were determined by high pressure liquid chromatography. Global isothermic ischemia of 20 min caused a release of endogenous noradrenaline amounting to 180 +/- 15 pmol/g. The calcium antagonists tested significantly suppressed ischemia-induced noradrenaline release (IC50 in mumols/l: verapamil 1, gallopamil 0.3, nifedipine 1, felodipine 3). Noradrenaline release during ischemia and the inhibitory effect of the calcium antagonists, were independent of extracellular calcium, indicating a nonexocytotic release mechanism. Interaction of the calcium antagonists with the major components of nonexocytotic release, intraneuronal storage and carrier mediated transport, was tested in normoxic rat hearts. Vesicular storage was not stabilized by the calcium antagonists. In fact, verapamil, gallopamil, diltiazem and felodipine disturbed storage function, as indicated by an increased DOPEG release. Direct interaction with the noradrenaline carrier (uptake1) was demonstrated for verapamil, gallopamil, and diltiazem in a model of 3H noradrenaline uptake. In conclusion, the calcium antagonists investigated inhibit noradrenaline release in ischemia by a mechanism which is different from blockade of neuronal calcium influx, and is rather due to an interaction with carrier mediated transport of noradrenaline across the plasma membrane. PMID- 1880813 TI - Distribution of myosin heavy chain mRNA in normal and hyperthyroid heart. AB - Hyperthyroid treatment produces rapid cardiac cell hypertrophy with all subcellular components increasing in an orderly manner. We compare normal and hyperthyroid tissue in order to relate changes in distribution of myosin mRNA during rapid assembly of myofibrils. At the light microscopic level, in situ hybridization of the ventricular cells shows myosin heavy chain mRNA to be distributed in a spoke-like pattern radiating from the nucleus. Electron microscopy provides the higher resolution necessary to determine mRNA distribution with respect to adjacent sarcomeric and cytoskeletal structures. Papillary muscles were removed from hyperthyroid and normal rabbits, aldehyde fixed, and embedded in LR white. Biotinated riboprobe transcribed from 0.5 kb in the coding region of terminal portion of the rod of alpha-myosin was hybridized and detected by immunocytochemical methods using 5 nm immunoglobulin G gold conjugates. Electron microscopy in situ hybridization runs with same-sense and anti-sense riboprobes were processed and ten micrographs randomly taken from each. Specific cytoplasmic densities of myosin mRNA were calculated by counting clusters of five or more gold particles over respective tissue components after subtraction of background counts. For both normal myocytes and hyperthyroid myocytes, the density of myosin mRNA was about 15 times higher in the cytoskeletal-rich inter-myofibrillar space than in the myofibrils. About half of the myosin mRNA in this inter-myofibrillar region is found within 10 nm of the peripheral filament, but no excess sarcomeric accumulation was seen beside the A Band. It appears that most of the myosin is translated from mRNA within the inter myofibrillar space along the entire length of the myofibril periphery. The emerging myosin heavy chain is not directly anchored to the thick filaments in either normal or rapidly growing cardiac cells. PMID- 1880814 TI - Intracellular sodium during ischemia and calcium-free perfusion: a 23Na NMR study. AB - Accumulation of sodium-ions (Na+) in myocardial cells during both ischemia and calcium (Ca2+)-free perfusion has been suggested to play an important role in the damage occurring during subsequent reperfusion and calcium repletion, respectively. We have used 23Na NMR spectroscopy in combination with shift reagents to determine intracellular Na(+)-concentration [( Na+]i) in isolated rat hearts during either control perfusion followed by ischemia and reperfusion, or during control perfusion, Ca(2+)-free perfusion and subsequent ischemia. [Na+]i during control perfusion was found to be 10.5 +/- 0.6 mmol/l. During 30 min of ischemia [Na+]i rose substantially to 25.0 +/- 3.2 mmol/l. During 15 min of reperfusion [Na+]i initially decreased, but leveled off after approximately 3 min and was 17.9 +/- 3.7 mmol/l at the end of the reperfusion period. Most surprisingly, however, no significant increase of [Na+]i was observed during 30 min of Ca(2+)-free perfusion, although severe calcium paradox damage was shown to occur under the used conditions, when calcium was readmitted to the heart. The absence of a rise of [Na+]i during Ca(2+)-free perfusion was substantiated when during subsequent ischemia a similar rise of [Na+]i was observed as during ischemia without previous Ca(2+)-depletion. We conclude that an increased [Na+]i during Ca(2+)-depletion is not a prerequisite for the calcium paradox to occur, but that increased [Na+]i during ischemia may influence the subsequent reperfusion damage through Na(+)-Ca2+ exchange. PMID- 1880815 TI - Effects of graded perfusion and isovolumic work on epicardial and venous adenosine and cytosolic metabolism. AB - Epicardial adenosine levels and venous adenosine release were measured in isovolumically contracting (ISO) and empty non-isovolumic (non-ISO) guinea-pig hearts subjected to graded perfusion (approximately 7.5, 5.5, 4.0, 2.0, and 1.0 ml/min/g). Myocardial metabolism was monitored using 31P-NMR spectroscopy. At flows of 5.5 ml/min/g or higher epicardial adenosine levels were stable and comparable in ISO and non-ISO hearts (approximately 160 nM). At flows of 4.0 ml/min/g or higher venous adenosine release was stable and comparable in ISO and non-ISO hearts (approximately 30 pmol/min/g). At lower flows, epicardial adenosine and venous adenosine release both increased and were significantly higher in ISO hearts, compared to non-ISO hearts, at each flow rate. Whereas epicardial adenosine increased linearly in ISO and non-ISO hearts at low flows, venous adenosine release stabilized in ISO hearts perfused at 1.0 ml/min/g. Epicardial adenosine, venous adenosine release, and log [ATP]/[ADP] [Pi] all displayed significant correlations with the O2 supply:demand ratio which were comparable in ISO and non-ISO hearts. Elevated levels of epicardial adenosine were linearly related to log [ATP]/[ADP] [Pi] and cytosolic [AMP] and these relationships were comparable in ISO and non-ISO hearts. Alternatively, changes in venous adenosine release did not display simple relationships with log [ATP]/[ADP] [Pi] and cytosolic [AMP] and they were not comparable in ISO and non ISO hearts. The data indicate that: (i) myocardial adenosine formation increases only below a metabolic threshold corresponding to log [ATP]/[ADP] [Pi] = 5.0 and O2 supply:demand = 1.5 in ISO and non-ISO guinea-pig hearts; (ii) stimulated epicardial adenosine levels appear to be consistently related to changes in cytosolic metabolism below this threshold in ISO and non-ISO hearts; (iii) more complex relationships exist between venous adenosine release and myocardial metabolism during graded perfusion, possibly reflecting the variety of factors modulating venous adenosine release. PMID- 1880816 TI - A novel positive inotropic substance enhances contractility without increasing the Ca2+ transient in rat myocardium. AB - We have investigated the mechanism of action of a novel positive inotropic agent, the thiadiazinone derivative 5-(1-(3,4-dimethoxybenzoyl)-1,2,3,4 tetrahydrochinolin-6-yl)-6- methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-on (EMD 53998). This substance inhibits phosphodiesterase III and, in skinned myocardial fibers, it increases myofilament sensitivity to Ca2+. However the effects of EMD 53998 on intact myocardial preparations are still undefined. In isolated rat hearts EMD 53998 (0.5 to 5 microM) had a dose-dependent effect to increase left ventricular systolic pressure. In isolated left ventricular myocytes loaded with the ester derivative of the Ca2+ probe indo-1, EMD 53998 (0.5 to 5 microM) enhanced twitch amplitude without increasing the associated indo-1 transient. The myofilament responsiveness to Ca2+ was assessed as the relationship between twitch and the indo-1 transient amplitudes as the latter is varied by altering the bathing [Ca2+], or stimulation pattern. EMD 53998 reversibly shifted this relationship to the left which indicates that for indo-1 transients of the same amplitude in the absence and presence of the drug, twitch amplitude was enhanced by EMD 53998. In isolated myocytes studied in the absence of electrical stimulation, EMD 53998. (1.5 to 5 microM) had a concentration-dependent effect to markedly and reversibly decrease cell length without increasing indo-1 fluorescence ratio. Thus, the cellular basis for the positive inotropic action of EMD 53998 in rat myocardium is related to the unique effect of this substance to enhance myofilament responsiveness to Ca2+ and not to an increase in the indo-1 transient amplitude. PMID- 1880817 TI - The human atrial trabecula: effects of calcium and temperature. AB - The human atrial trabecular preparation is an in vitro model which has been used to evaluate drugs and conditions to which cardiac muscle is exposed perioperatively. During its development, modifications have been made to this preparation. Two important components affecting myocardial muscle contraction are temperature and calcium concentration of the muscle bath medium. Previously, these parameters were determined independently of one another and found to be 34 degrees C and 2.5 mM calcium in a minimal Tyrode's buffer with glucose. This study was undertaken to define the optimal temperature and calcium concentration which would result in the highest yield of muscles that satisfied rigorous criteria for acceptability: developed force (DF) greater than 0.8 g, resting force (RF) less than 0.7 g, cross-sectional area less than or equal to 1.0 mm2). A total of 134 trabeculae were tested using a modified Krebs-Henseleit buffer, enriched with Eagles' medium and containing either 1.25 or 2.5 mM calcium at 34 or 37 degrees C. The trabeculae contracting in 2.5 mM calcium at 37 degrees C resulted in the highest yield of 26% while those maintained at 34 degrees C in either 1.25 or 2.5 mM calcium led to 20 and 15% useful preparations respectively (P = N.S.). Trabeculae contracting at 37 degrees C in 1.25 mM calcium resulted in the poorest yield of 8% (P = 0.002). There is a small (5 to 7%), but significant (P = 0.02), decrease in DF in 1 h when all groups were analyzed together. The exclusion criteria which are applied eliminate variability due to disease and/or treatment, therefore only 20 to 25% are acceptable for study. In summary, with well-defined and stringently applied criteria, the human right atrial trabecular preparation can be a reliable and reproducible model functioning at 37 degrees C and 2.5 mM calcium for a variety of studies. PMID- 1880818 TI - Further studies on the influence of cAMP-dependent protein kinase on junctional conductance in isolated heart cell pairs. AB - The influence of the catalytic subunit (20 micrograms/ml) of cAMP-dependent protein kinase on junctional conductance (gj) of isolated rat ventricular cell pairs was investigated. It was found that gj was increased by 90% within 4 to 5 min when the subunit was dialysed into both cells. The dialysis of the catalytic subunit into just one cell of the pair increased gj and generated rectification of junctional membrane. The regulatory subunit (20 micrograms/ml) of cAMP dependent protein kinase reduced gj by about 17% when dialysed into both cells of pairs. These results might indicate that the symmetric phosphorylation of junctional proteins in the two hemichannels increases gj without rectification while asymmetric phosphorylation generates rectification of junctional membrane. PMID- 1880819 TI - Coronary pressure determines regional glucose uptake in the left ventricular wall of the heart. AB - The effect of coronary and intraventricular pressures on the glucose uptake and its transmural distribution was studied in isolated, beating rat heart perfused using the Langendorff procedure. Left ventricular glucose uptake measured by the deoxyglucose method, and the effect of coronary (aortic) pressure was dissociated from intraventricular pressure development by draining the left ventricle. Left ventricular glucose uptake was 2.6 +/- 0.1 mumols/min per g protein (mean +/- S.E.M.) and 35 +/- 6% higher (P less than 0.001) in the subendocardium than in the subepicardium under control conditions (aortic pressure 80 cm H2O, non drained). Elimination of the intraventricular pressure development caused no significant change in the total left ventricular glucose uptake or its transmural distribution. Increase in the aortic pressure to 150 cmH2O accelerated glucose uptake in non-drained and drained hearts by 57-75%. The increase in the glucose uptake was more pronounced in the subepicardial layer than in the subendocardial layer, so that the transmural gradient decreased by 27-32% (P less than 0.001) in non-drained and drained hearts. The results indicate that in Langendorff-perfused heart the effect of aortic pressure on the total glucose uptake and its transmural distribution across the left ventricular wall is not mediated through intraventricular pressure development, but through the coronary pressure. PMID- 1880820 TI - Program and abstracts of the XIIth meeting, (European section) of the International Society for Heart Research, Leuven, Belgium, 10-13 September 1991 and program and abstracts of the satellite meeting of the XIIth meeting (European section) of the International Society for Heart Research, Utrecht, The Netherlands, 9-10 September 1991. PMID- 1880821 TI - Study on the pH of ogi, Nigerian fermented weaning food, and its effect on enteropathogenic Escherichia coli, Salmonella typhi and Salmonella paratyphi. AB - The pH values of both cooked and uncooked ogi samples were determined and the survival of nalidixic acid-resistant enteropathogenic Escherichia coli OB 26 34/20, Salmonella typhi and Salmonella paratyphi A when seeded into cooked ogi were studied. The pH values of ogi ranged from pH 3.0 to 3.9. Cooked ogi had a slightly lower pH value than uncooked ogi. Our survival experiments showed that the inoculated enteric pathogens were considerably inhibited in cooked ogi during storage for 24 h. The antibacterial effect of cooked ogi was more pronounced on enteropathogenic E. coli with a log10 5 decline in bacterial count within 6 h. PMID- 1880822 TI - Assessing diarrhoea-induced dehydration at the community level. AB - A community based study of children under 5 years of age in Nampula, Mozambique, assessed children with diarrhoea for the 12 signs and symptoms of dehydration listed in the World Health Organization's Diarrhoea Treatment Chart and for the additional indicators of observed thirst and reported fever. The point prevalence of diarrhoea was 13.1%. The signs and symptoms of dehydration reported by carers were compared with signs detected on physical examination at the time of the interview. The presence of four or more stools, a history of drinking either more or less than usual, and reported fever in the preceding 24 h had the highest sensitivities. Individual symptoms with the highest specificity were decreased urine output, vomiting, and the passing of 10 or more stools during the 24 h preceding the interview. The combination of fever or vomiting had a sensitivity of 68.3% and a specificity of 55.9%, whereas a combination of vomiting or drinking more than usual or fever had a sensitivity of 87.8% and a specificity of 34.1%. These findings are compared with the results of similar studies conducted in different clinical and cultural settings. PMID- 1880823 TI - Consecutive stings by red scorpions evoke severe cardiovascular manifestations in the first, but not in the second, victim: a clinical observation. AB - Three pairs of scorpion sting victims ((1) daughter and mother, (2) brother and sister and (3) brother and sister) were admitted. In each pair, both were stung by the same scorpion. A patients from each pair were the first stung (initial sting), B patients the second. All A victims of the three pairs had cardiovascular manifestations: hypertension, with pulmonary oedema; hypotension bradycardia, pulmonary oedema; and hypertension respectively. B victims from the three pairs suffered no systemic or cardiovascular involvement, only severe excruciating local pain at the sting site. It is concluded that A victims received a large dose of venom, injected by the scorpion virtually evacuating the telson resulting in an 'autonomic storm' and severe cardiovascular involvement. PMID- 1880824 TI - Guinea-pig ileal loop assay: a better replacement of the suckling mouse assay for detection of heat-stable enterotoxins of Escherichia coli. AB - The suitability of guinea-pig ileal loop assay (GILA) for the assay of heat stable (ST) enterotoxin was confirmed. Secretory response against Escherichia coli heat-stable enterotoxin in this model was determined in terms of dilatation index (DI). DI equal to 0.50 or more was considered as a positive secretory response. Kinetics of fluid accumulation and the titration of toxin in guinea-pig ileal loop suggest uniform secretory response throughout the small intestine and 31.5 microgram of crude ST toxin as the minimum effective dose to induce a DI of 0.5. Guinea-pig intestine was found sensitive to both methanol soluble (STa) and methanol insoluble (STb) toxins of E. coli and so was considered superior to the existing suckling mouse assay (SMA), which is known to be sensitive only to STa toxin. In addition, GILA was also found to be more suitable and economical as at least 10 strains together with the positive and negative controls can be tested in one animal, whereas in SMA, four suckling mice were needed to test a single strain. Hence, in SMA individual susceptibility among mice cannot be ruled out. GILA was considered to be an alternative to the presently available test, SMA, in the determination of ST toxin of E. coli. PMID- 1880825 TI - Can anopheline-transmitted filariasis be eradicated? PMID- 1880826 TI - Threshold of transmission of Brugia malayi by Anopheles sinensis. AB - In an area of central China where Brugia malayi is transmitted by Anopheles sinensis, three villages were followed for 4 years without any control measures. Diethylcarbamazine (DEC) had been used in a control programme reducing the parasite rate in Shuiwa from 12.72 to 0.59%, in Gubomen from 3.18 to 1.55% and in Moshi from 5.62 to 2.81% (although this fell the following year to 2.23%) up until the start of the trial. The village populations, the human biting rate, the parous and the gonotrophic cycle were comparable for all the areas, yet the microfilariae rate dropped to 0.18% in Shuiwa, 0.31% in Gubomen, but not in Moshi where it increased from 2.23 to 2.43%. This indicated that Shuiwa and Gubomen were below the threshold of transmission. Due to the small number of positive cases remaining, the density measurements showed less change, but a separate study on 44 individuals followed for 6 years revealed that those above 13 microfilariae per 60 mm3 remained unchanged or increased, while those below progressively decreased their densities. The threshold of transmission of B. malayi by An. sinensis was considered to be between 1.55 and 2.23% of the population, providing no individual had a higher density than 12 microfilariae per 60 mm3. PMID- 1880827 TI - Red blood cells' auto-agglutination as an indicator test in human trypanosomiasis. AB - Spontaneous red blood cells' auto-agglutination was assessed as an indicator for the diagnosis of human African trypanosomiasis. This test is easily carried out by health workers with minimum qualification. It presents a high sensitivity (0.91) and a high predictive value of a negative result (0.99). Although a positive result gives a low indication of infection, the health care workers should refer the patient to a screening centre. PMID- 1880828 TI - The relationship of microbial pathogens to acute infectious diarrhoea of childhood. AB - Bacterial, viral and parasitic enteric pathogens were detected in 692 of 916 children below 36 months of age with acute diarrhoea and in 289 of 587 matched controls. The rates of identification of only four groups of pathogens, rotavirus, Shigellae, Salmonella typhimurium and enterotoxigenic E. coli, were significantly higher in the patients. The prevalence of a variety of other enteric pathogens was similar in controls of patients. Shigellosis had a characteristic clinical profile but none of the other agents could be suspected on clinical grounds. The high prevalence of pathogens in controls suggested that the population may be partially protected against a variety of enteric pathogens and that final common pathways leading to diarrhoea may be activated by changes in the microbial ecology of the gut lumen. PMID- 1880829 TI - The epidemiology of echinococcosis in Israel. AB - Shifts in population and employment patterns in Israel since 1948 have been accompanied by profound changes in the distribution of echinococcal disease. Formerly, it was most commonly imported with the mass immigration of Jews after 1948 from the Arab countries of North Africa and Asia Minor, and appeared to be relatively uncommon in Israel-born Jews and Arabs. In 1980 the disease was made notifiable, and this paper presents a review of the years 1981-1989. The prevalence pattern that prevailed after the end of mass immigration has reversed so that cases are now twice as common in Arabs as in Jews. Among the Arabs the disease appears most commonly in the north of the country, especially among the Druze, less commonly among Christians and least in Muslims. We suggest that this prevalence pattern is related largely to home slaughter of sheep, to differing attitudes to dogs, and possibly also to the hunting of wild pig. Targetted education and better enforcement of existing regulations can lead to a reduction in disease. PMID- 1880830 TI - Utilization of village health workers within a primary health care programme in The Gambia. AB - The utilization of Village Health Workers (VHWs) was studied in a rural area of The Gambia 3 years after the introduction of a village-based Primary Health Care (PHC) programme. Of 23 children who died from conditions treatable at village level, only five were first seen by the VHW. Fourteen were seen elsewhere in the region by staff more qualified than the first tier workers. The implications of this pattern of utilization on the lack of impact of VHWs on mortality are discussed. Only half of the non-fatal illnesses were attended to by VHWs. Reasons for this included such factors as lack of knowledge of services available, shortages of money, absence of the VHW at critical periods and social or political disputes with VHWs. Attempts must be made to tackle these fundamental problems if VHWs are to be successfully incorporated into the health services. PMID- 1880831 TI - A standardized schedule for burden on the family of sickle-cell anaemia sufferers. AB - The chronicity and incurability of sickle cell anaemia reinforce the need to give particular attention to the psychosocial effect of the illness on the family. A 22-item schedule of burden with very high inter-rater reliability and modest validity is constructed and should be useful in the assessment of other similar chronic disorders. The phylogenetic origin of sickle-cell anaemia makes it essential that a psychological understanding of the disorder should be a component of the therapy arsenal of health professionals serving populations of African extraction. PMID- 1880832 TI - A new realistic index of experimental transmission efficiency for Bancroftian filariasis. AB - An index for experimental transmission of filariasis infection was first introduced by Kartman and subsequently modified by Wharton who defined it as 'the number of infective larvae per mosquito when the microfilaria count is 1.0 mm-3 of human blood'. Since mosquitoes may not imbibe the expected number of microfilariae from the donor's blood during feeding because of various interference phenomena and/or mechanisms, this paper presents the index mosquito meal (Index MM), based on the actual number of viable microfilariae that are observed in the mosquito gut immediately after feeding. The Index MM is defined as 'the number of infective larvae per mosquito when the microfilaria count is 1.0 mm-3 of mosquito blood meal'. The Index MM proved to be a more valid indicator of transmission potential than the Wharton Index when applied to the data of two controlled field studies where groups of laboratory-reared Culex pipiens molestus, the primary vector of filariasis in Egypt, were fed on volunteers having different microfilaraemic densities. PMID- 1880833 TI - Results of a multicenter study of the modified hook-titanium Greenfield filter. AB - Initial efforts to modify the stainless steel Greenfield filter for percutaneous insertion led to development of a titanium Greenfield filter, which could be inserted by use of a 12F carrier. This device functioned well as a filter but had an unacceptable 30% rate of migration, tilting, and penetration. Therefore a titanium Greenfield filter with modified hooks was developed and has been tested in 186 patients at 10 institutions. Successful placement occurred in 181 (97%); placement of the remainder was precluded by unfavorable anatomy. A contraindication to anticoagulation was the most frequent indication for insertion (75%). All but two were inserted percutaneously, predominantly via the right femoral vein (70%). Initial incomplete opening was seen in four patients (2%), which was corrected by guide wire manipulation and asymmetry of the legs in 10 (5.4%). Insertion site hematoma occurred in one patient, and apical penetration of the cava during insertion occurred in a second patient. Both events were without sequelae. Follow-up examinations were performed at 30 days at which time 35 deaths had occurred. Recurrent embolism was suspected in six patients (3%) and two of three deaths were confirmed by autopsy. Filter movement greater than 9 mm was seen in 13 patients, (11%) and increase in base diameter greater than or equal to 5 mm was seen in 17 patients (14%). CT scanning showed evidence of caval penetration in only one patient (0.8%). Insertion site venous thrombosis was seen in 4/46 (8.7%) patients screened. The modified hook titanium Greenfield filter is inserted percutaneously or operatively through a sheath, eliminating concern for misplacement from premature discharge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880834 TI - Early and late geometric changes after carotid endarterectomy patch reconstruction. AB - This study examines the degree and location of vessel wall geometric changes after carotid endarterectomy-vein patch reconstruction. The external diameters of the proximal common carotid, common carotid bulb, and internal carotid arteries were measured during operation with a caliper after 349 carotid endarterectomies. There were 309 saphenous vein reconstructions, 31 synthetic patch reconstructions, and 9 primary closures. One or more B-mode ultrasound studies with cross-sectional views for common and internal carotid cursor measurements were performed from 3 months to 5 years after operation. The intraoperative-to postoperative common carotid diameters were unchanged for the three types of reconstructions. The internal carotid diameters increased 20% to 30% for both the vein and synthetic patched arteries. This dilation was present at 3 and 6 months and progressed slightly over 5 years. Wall thickening greater than or equal to 1 mm was present in 62% of the carotid endarterectomies, with concentric stenosis in 3% and eccentric stenosis in 59%. Eccentric stenosis was present at 3 to 6 months, located on the endarterectomized posterior-medial wall of the common and internal carotid arteries, was always less than 50%, and changed very little over 5 years. No aneurysms or internal carotid occlusions were identified. Carotid endarterectomy-vein patch reconstruction results in early, mild, nonaneurysmal dilation of the internal carotid patched segment, frequent mild eccentric restenosis, and rare hemodynamically significant concentric restenosis. PMID- 1880835 TI - A prospective study of respiratory failure after high-risk surgery on the thoracoabdominal aorta. AB - From June 1960 to September 1990, 1414 patients underwent repair of thoracoabdominal aortic aneurysms, of whom 112 (8%) had pulmonary complications requiring respiratory support with tracheostomy; subsequently 45 (40%) died in the hospital. We determined by stepwise logistic regression analysis, in a prospective study of high-risk type I and II thoracoabdominal aortic aneurysms repairs, the independent predictors of respiratory failure, defined as respiratory ventilation exceeding 48 hours after operation. In 98 patients studied, 38 (39%) were women, 60 (61%) were men, 54 (55%) had type II thoracoabdominal aortic aneurysms, 34 (35%) had aortic dissection, 19 (19%) were nonsmokers, 40 (41%) exsmokers, and 39 (40%) active smokers. Before operation, 55 (56%) had chronic pulmonary disease with respiratory failure developing in 58% (p = 0.0005 versus no chronic pulmonary disease, 10/43, 23%), and of the 26 patients in the lower quarter of forced expiratory volume (1 sec) (FEV1 less than or equal to 1.45 L) respiratory failure developed in 61% (p = 0.035). In-hospital survival was 98% and 83% (p = 0.008), respectively, and cumulative survival at 6 months by Kaplan-Meier analysis was 96% and 80% (p = 0.004, log-rank test), respectively, for patients without respiratory failure (N = 56/98, 57%) and with respiratory failure (N = 42/98, 43%). On univariate analysis, the following were associated with respiratory failure (p less than 0.05): FEV1, FEV1% predicted, FVC, FEF25, FEF25% predicted, FEF25-75, FEF25-75% predicted, PaCO2 Pao2, symptoms, smoking history, chronic pulmonary disease, cryoprecipitate volume, postoperative neuromuscular deficit, cardiac complications, reoperation for bleeding, renal complication, stress ulceration, postoperative creatinine level, postoperative dialysis, and postoperative encephalopathy. The independent predictors of respiratory failure were (p less than 0.05): chronic pulmonary disease, smoking history, cardiac and renal complications. In patients with chronic pulmonary disease, the only independent predictor was FEF25 (p = 0.030). These observations may be of value in selecting patients for elective operation. PMID- 1880836 TI - Value and limitations of secondary femoropopliteal bypasses with polytetrafluoroethylene. AB - Secondary femoropopliteal bypasses with polytetrafluoroethylene (PTFE) grafts are widely regarded to be of questionable value. This has prompted some to abandon all attempts at secondary revascularization with PTFE and others to recommend that primary femoropopliteal bypasses be performed preferentially with PTFE grafts so that vein may be used for secondary procedures. Because we questioned both of these views, we reviewed all femoropopliteal bypasses done at our institution in the past 12 years and identified 73 secondary PTFE femoropopliteal procedures performed after a failed ipsilateral infrainguinal bypass (69 failed femoropopliteal; 4 failed femorodistal). Seventy (96%) secondary bypasses were performed for limb salvage and 3 (4%) for severe disabling claudication. Insertion of grafts to the popliteal artery was above the knee in 26 (36%) and below the knee in 47 (64%). Primary life-table graft patency at 4 years was only 38%. Forty-eight reinterventions in 34 limbs were required to restore or maintain graft patency in thrombosed or failing grafts. For thrombosed grafts, 20 interventions consisted of 9 simple thrombectomies and 11 thrombectomies with additional revision procedures (5 distal or proximal extensions, 6 patch angioplasties). Twenty-eight lesions threatening graft patency were treated by percutaneous transluminal angioplasty in 3, proximal or distal extensions in 20, and patch angioplasty in 5. As a result of these reinterventions, the overall secondary patency rate was 55% at 4 years, and the limb salvage rate was 74% at 4 years. Although aggressive follow-up and reintervention may be required, the use of secondary PTFE conduits in the femoropopliteal position is a viable option in patients undergoing limb salvage procedures who are at high risk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880837 TI - The natural history of superficial femoral artery stenoses. AB - Since the natural history of specific superficial femoral artery stenoses is not known, we examined progression rates of superficial femoral artery stenoses in 45 lower extremities found when arteriograms were obtained of 38 patients for symptomatic atherosclerotic disease in the opposite leg or abdomen. These initial superficial femoral artery arteriograms were compared with later arteriograms in 25 limbs, duplex scans in 27 limbs, and both modalities in 7 limbs. After a mean interval of 37 months, most superficial femoral artery stenoses (72%) did not progress. However, 12 superficial femoral artery stenoses progressed (28%; mean follow-up, 37 months, including 7 that occluded (17%). Superficial femoral artery stenoses progressed among patients who complained of symptom progression at a rate faster than that among asymptomatic patients (15.6%/year vs 3%/year; p = 0.006). Superficial femoral artery lesions also progressed more rapidly among patients whose contralateral superficial femoral artery was occluded (10%/year vs 1.6%/year; p = 0.04). By multivariate regression analysis, symptom progression and smoking history were predictive of superficial femoral artery stenosis progression. In the seven patients whose superficial femoral artery stenoses progressed to occlusion, the average rate of stenosis progression was 12%/year (maximum predicted rate, 30% per year by 95% confidence limit). These results indicate that superficial femoral artery stenoses usually progress with synchronous symptomatic deterioration. Other than symptom progression, only cumulative smoking history and contralateral superficial femoral artery occlusion could be associated with superficial femoral artery stenosis progression in this small series.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880838 TI - Venous obstruction: an analysis of one hundred thirty-seven cases with hemodynamic, venographic, and clinical correlations. AB - One hundred thirty-seven limbs with venous obstruction were analyzed. The arm/foot venous pressure differential and reactive hyperemia tests were found to be useful techniques to diagnose and grade venous obstruction. Traditional techniques including venography and ambulatory venous pressure are inferior in this regard. The newer techniques have provided newer insights in venous obstruction which are detailed herein. The hand-held Doppler was surprisingly very sensitive in grade I as well as in more severe forms of obstruction. Neither anatomic locale of obstruction nor its extent determined hemodynamic severity. Extensive proximal lesions could be hemodynamically mild, and conversely distal crural obstructions and single segment lesions could be hemodynamically severe. Phlebographic appearance was a poor index of collateralization. The paradoxical venous pressure response to the reactive hyperemia test in grade IV obstruction was found to be due to suppression or delay of the reactive hyperemia response itself in the presence of severe venous obstruction. The pain of venous claudication may be related to this phenomenon. Skin ulceration in the presence of venous obstruction was related to the associated reflux rather than the hemodynamic severity of the obstruction itself. The Linton procedure was found to be useful in treating such skin ulcerations. After perforator disruption, obstruction did not become hemodynamically worse, but reflux as measured by the Valsalva test improved with ulcer healing. The improvement in reflux related to Valsalva offers for the first time a hemodynamic rationale for the Linton procedure. PMID- 1880839 TI - Vascular trauma as a result of therapeutic procedures for the treatment of malignancy. AB - Twenty-two iatrogenic vascular injuries caused by resection of tumors with local recurrences or adjuvant chemotherapy were treated over a 42-month period in 11 female and 8 male patients with cancer (58% had documented metastases). Sixteen of 22 vascular injuries were caused by intraarterial administration of chemotherapy (8 emboli; 8 direct catheter trauma), and six were caused by resection of tumors with local invasion. The injuries were extremity ischemia (15 extremities in 13 patients), pseudoaneurysm (4), expanding hematoma (3 injuries in 2 patients). Twenty-two surgical repairs included bypass of severely damaged arteries in five, embolectomy in five, interposition grafts in three, pseudoaneurysm resection and primary repair in three, primary repair of three vascular injuries, and one patch angioplasty. Leg amputation was required in two patients. Seventeen of 19 patients had successful vascular repairs with resolution of preoperative indications for vascular repair without intraoperative or postoperative deaths. Long term follow-up (mean, 17 months) showed no recurrence of vascular problems; however, two patients died of metastatic cancer at 6 and 24 weeks after vascular repair. This study supports an aggressive approach to the management of vascular injuries caused by therapeutic interventions for malignancy despite the presence of metastatic disease. PMID- 1880840 TI - Vascular rehabilitation: benefits of a structured exercise/risk modification program. AB - A vascular rehabilitation program was designed to increase exercise tolerance and reduce the risk of cardiovascular disease in patients with lower extremity arterial occlusive disease. Sixty-eight patients (32 men, 36 women); ages 55 to 85 years (mean, 68 years) with claudication 30 (44%), or recovering from lower extremity revascularization 36 (53%), or endovascular procedures 2 (3%) entered the vascular rehabilitation program. Each underwent a physical examination, risk factor assessment, noninvasive arterial studies, and cardiac evaluation. A history was taken from each patient also. Six patients (9%) were excluded on recognition of silent myocardial ischemia. Sixty-two patients (91%) were accepted for exercise training in a program designed to offer 24 (1-hour) monitored exercise sessions, 12 (1-hour) personalized education lectures, and development of a home maintenance exercise program. No deaths or major morbidity occurred. Seventeen patients (27%) did not finish the program, eight (13%) because of development of significant cardiac, extremity, or cerebrovascular disease and nine for nonmedical reasons. Of the 45 patients (73%) who completed the program, 38 (88%) had documented increases in walking distances of greater than 100% (122% to 450%). All 45 patients designed home exercise programs, and 88% of the smokers quit. Long-term follow-up was available on 100% of the patients. Thirty-eight patients (84%) have been followed for 2 years or more. Thirty-eight (84%) maintained or improved walking distances recorded on exit from the program. Thirty of the 36 patients (83%) who stopped smoking remained nonsmokers. Significant reductions in cholesterol were seen at 1 year, and significant reductions in triglycerides were seen at 12 weeks and 1 year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880841 TI - Natural history of atherosclerotic renal artery stenosis associated with aortic disease. AB - The natural history of atherosclerotic renal artery stenosis has not been well defined, particularly when discovered in conjunction with aortic disease requiring correction. To better define the natural history of such lesions, 194 sequential aortograms in 48 patients were studied to define predictive criteria for stenoses at risk for progression. Sixty-six unsuspected atherosclerotic renal arterial stenoses were identified on the initial aortograms. Disease progressed in 42 arteries (53%), 14 bilateral and 28 unilateral. Seven arteries developed occlusion. All had stenoses averaging 80% (range 61% to 94%) noted on the most recent aortogram preceding occlusion. Risk factors including smoking, diabetes mellitus, elevated serum lipids, coronary artery disease, peripheral arterial disease, or change in blood pressure or creatinine, did not correlate with degree or rate of progression of the renal artery stenosis. A difference in kidney size, although varying inversely with degree of stenosis, was not a statistically significant marker of disease progression. This analysis suggests that identification of renal arterial stenoses that will progress is best determined by sequential aortography. Highly stenotic vessels are more prone to occlude than those less stenotic. Consequently, individuals with preocclusive lesions should benefit from prophylactic renal revascularization during aortic reconstruction. PMID- 1880842 TI - Noninvasive diagnosis of vascular trauma by duplex ultrasonography. AB - Duplex ultrasonography was used prospectively in the initial evaluation of 198 patients with 319 potential vascular injuries of the neck and extremities. Patients who were unstable or who had obvious arterial trauma were excluded. Injury was caused by gunshot in 104 (53%), blunt trauma in 42 (21%), stab wound in 34 (17%), and shotgun in 18 (9%). Duplex ultrasonography correctly characterized and localized vascular injuries in 23 patients: arterial disruptions (13), intimal flaps (4), acute pseudoaneurysms (3), arteriovenous fistulas (2), and shotgun pellet arteriopuncture (1). Nineteen other patients had vasospasm (13) or external compression (6) without evidence of intrinsic vessel injury, these 42 studies had true-positive results. Twenty patients underwent arterial repair (13 on the basis of duplex ultrasonography alone), one had primary amputation, three required fasciotomy, and 18 were observed. Two patients with false-negative results had minor shotgun pellet arteriopunctures that were missed by duplex ultrasonography, but neither needed repair. One hundred fifty three patients had true-negative results on duplex ultrasonography: all clinically had only proximity injuries and easily palpable distal pulses. The result of one duplex ultrasonography study was found to be false-positive on arteriography. The sensitivity of duplex ultrasonography was 95%, the specificity was 99%, and the overall accuracy was 98%. These results closely approximate those reported with the use of exclusion arteriography in the evaluation of similar vascular trauma patients. Furthermore, duplex ultrasonography has no interventional risks and is more cost-effective for screening such injuries than arteriography or exploration. Duplex ultrasonography is a reliable method of diagnosis in patients with potential peripheral vascular injuries. PMID- 1880843 TI - Quantitation of vascular outflow by measurement of impedance. AB - One of the most important determinants of graft patency is the degree and character of vascular outflow. This study was designed to evaluate input impedance as a functional assessment of the outflow bed of vascular grafts. Four distinct outflow environments were created for external jugular vein conduits in 42 New Zealand white rabbits. Vein grafts (n = 14) were fashioned as end-to-side common carotid interposition bypass grafts. Arteriovenous fistulas (n = 15) were created by side-to-side anastomosis of the distal common carotid artery and linguofacial vein. Arteriovenous fistulas with outflow obstruction (n = 7) were fistulas with a metal clip partially obstructing the distal outflow channel (1 mm lumen). Vein graft/arteriovenous fistula combinations (n = 6) consisted of a vein graft and arteriovenous fistula in series. Pressure and flow in the external jugular vein were measured, and input impedance spectra were calculated by Fourier methods. By use of a PC-based acquisition and processing system, impedance results for 20 cardiac cycles could be obtained in approximately 10 minutes. The results revealed that vein grafts typically demonstrated high resistance to steady state flow (Rin = 235 +/- 50 x 10(3) dyne . sec/cm-5) and steadily decreasing impedance to pulsatile flow resulting in a characteristic impedance (Z0; average of fourth to tenth harmonics) of 35.5 +/- 8.0 x 10(3) dyne . sec/cm-5. Phase angle values were usually negative, especially at low harmonics (first harmonic phase angle = -1.11 +/- 0.10 radians) indicating that flow led pressure. In contrast, arteriovenous fistula Rin was minimal (6.3 +/- 1.4 x 10(3) dyne . sec/cm-5; p less than 0.05 compared to vein graft, and the impedance was flat across the frequency spectrum (Z0 = 8.5 +/- 1.5 x 10(3) dyne . sec/cm-5; p less than 0.05) with pressure and flow nearly in phase (first harmonic phase angle = -0.05 +/- 0.10 radians). Creation of outflow obstruction in arteriovenous fistulas resulted in significantly elevated Rin (136 +/- 41 x 10(3) dyne/sec . cm 5; p less than 0.05 compared to arteriovenous fistula and Z0 (23 +/- 9 x 10(3) dyne . sec/cm-5, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1880844 TI - Intraoperative duplex sonography during renal artery reconstruction. AB - To assess renal duplex sonography as an intraoperative study to detect technical defects during repair, 57 renal artery reconstructions in 35 patients were studied. Sixteen men and 19 women (mean age, 62 years) underwent unilateral (13 patients) or bilateral (22 patients) renal artery repair to 57 kidneys. Methods of repair included aortorenal bypass grafting in 29 cases (20 saphenous vein, 5 polytetrafluoroethylene, 4 Dacron), reimplantation in 7, transrenal thromboendarterectomy with patch angioplasty in 13, and transaortic extraction thromboendarterectomy in 8. Branch renal artery repair was required in six cases (five in vivo, one ex vivo). Fourteen patients had combined aortic replacement (11 patients: 8 abdominal aortic aneurysms, 3 aortic occlusions) or visceral artery reconstruction (three patients: three superior mesenteric artery thromboendarterectomies, one inferior mesenteric artery thromboendarterectomy). Intraoperative renal duplex sonography (mean scan time, 4.5 minutes) was complete in 56 of 57 repairs (98%), and renal duplex sonography was normal in 44 repairs (77%). Overall, B-scan defects were present in 13 repairs (23%). Six of these (11%) were defined as major B-scan defects by Doppler spectra with focal increases in peak systolic velocity greater than or equal to 2.0 meters/sec (major defect, mean renal artery peak systolic velocity, 3.1 m/sec), which prompted immediate operative revision. Seven B-scan defects were defined as minor by Doppler spectra (minor defect, mean renal artery, peak systolic velocity, 0.7 m/sec) and were not revised. Postoperative evaluation (range, 1 to 22 months; mean follow-up, 12.4 months) of 55 renal artery repairs in 34 operative survivors (surface renal duplex sonography, 33 patients; renal angiography, 9 patients) demonstrated 42/43 renal artery repairs with normal intraoperative renal duplex sonography, and 6/6 repairs with minor B-scan defects were patent and free of critical stenosis. Of the 6 renal artery revisions prompted by major B-scan defects, 4 remained patent, 1 stenosed, and 1 occluded. Our experience suggests that intraoperative renal duplex sonography during renal artery repair provides valuable anatomic and physiologic information. Renal artery repairs with normal renal duplex sonography and minor B-scan defects without Doppler spectral changes demonstrated 98% patency without critical stenosis at 12.4 months of mean follow up. However, major B-scan defects defined by a focal increase in renal artery peak systolic velocity should be considered for immediate correction. PMID- 1880845 TI - Vascular complications of cardiac catheterization. AB - Femoral artery injury after diagnostic and therapeutic cardiac catheterization is a frequently encountered clinical problem. This study reviews 150 femoral artery injuries that occurred in 16,350 patients over a 5-year period. A prospective computerized cardiac catheterization data bank was used to determine significant risk factors associated with the occurrence of vascular injury. Logistic regression analysis revealed that congestive heart failure, female gender, and percutaneous transluminal coronary angioplasty or valvuloplasty procedure were significantly associated with occurrence of vascular injury. Greater age, smaller body surface area, and smaller weight were also associated with injury. Recommendations for management include an aggressive approach to obstruction even if local vascular reconstruction is required. False aneurysms are studied by ultrasonography, and small ones may be observed expectantly. Larger aneurysms and aneurysms that persist beyond a few days are managed by use of general or regional anesthesia and by gaining proximal control of the iliac artery. Arteriovenous fistulas resulting from catheterization are rarely hemodynamically significant and often close spontaneously. Thus repair should be delayed. PMID- 1880846 TI - Postoperative vasospasm after antegrade mesenteric revascularization: a report of three cases. AB - Vascular reconstruction for chronic intestinal ischemia can be accomplished by endarterectomy or aortomesenteric bypass. In our practice, antegrade bypasses from the supraceliac aorta to the celiac axis and superior mesenteric artery are currently the most frequently used techniques. Such reconstructions often use multiple or bifurcated large diameter vascular prostheses and have demonstrated excellent long-term patency. Despite these salutory results, we have noted an unusual perioperative response in three of these patients, which is the subject of this report. All three patients underwent uncomplicated elective mesenteric revascularization with grafts (diameter greater than or equal to 6 mm) originating in the supraceliac aorta. Indications for operation included (1) history of postprandial pain, (2) documentation of weight loss, and (3) angiographic evidence of advanced atherosclerotic disease with appropriate collateral development. Episodes of abdominal pain occurred 5 to 20 days after operation when normal food intake was reinstituted. In two patients immediate angiograms revealed patent grafts with diffuse mesenteric vasospasm. Treatment with intravenous hyperalimentation and nifedipine for 10 days resulted in complete resolution of symptoms. In the third patient, symptoms were totally relieved by temporary reduction in oral intake and administration of nifedipine. A later angiogram revealed a patent graft. All patients have remained asymptomatic and regained normal weight. This pattern of postrevascularization pain has not been seen in our patients undergoing revascularization with small (i.e., venous) conduits originating in the infrarenal aorta. The cause appears to be a heightened myogenic response of a "protected" vascular bed when suddenly exposed to the high perfusion pressure and blood flow of large caliber antegrade conduits. Prophylaxis with calcium channel blockers and use of smaller diameter grafts (5 mm) may avoid this disturbing syndrome. PMID- 1880847 TI - Late results of two hundred seventeen femoropopliteal bypasses to isolated popliteal artery segments. AB - A 10-year-experience of 217 femoropopliteal bypasses to isolated popliteal artery segments in 207 patients is reported. Thirty-three femoropopliteal bypasses (15%) were performed with reversed saphenous vein and 184 (85%) with polytetrafluoroethylene grafts. Operative indications were gangrene in 121 (56%), nonhealing ulceration in 40 (18%), ischemic rest pain in 51 (24%), and claudication in 5 (2%) cases. The 5-year primary graft patency rate of these bypasses was 59% (reversed saphenous vein, 74%; polytetrafluoroethylene, 55%; p less than 0.05), the secondary 5-year graft patency rate was 61% (reversed saphenous vein, 79%; polytetrafluoroethylene, 56%; p less than 0.05), and the 5 year limb salvage rate was 78% (reversed saphenous vein, 78%; polytetrafluoroethylene, 78%). The 30-day operative mortality rate was 10%, and the 5-year patient survival rate was 38%. Eleven patients (5%) required lower extremity amputation because of progressive gangrene or extensive infection despite a patent bypass to an isolated popliteal artery segment. We conclude that femoropopliteal bypasses to isolated popliteal artery segments (1) have acceptable 5-year graft patency and limb salvage rates; (2) should be performed with reversed saphenous vein grafts when possible; (3) may be performed with polytetrafluoroethylene grafts if necessary, with a resulting limb salvage rate equal to that of reversed saphenous vein grafts; and (4) require sequential extension to an infrapopliteal artery in up to 20% of patients. In addition, the presence of an isolated popliteal artery segment is associated with a high operative mortality rate and limited life expectancy because of coronary artery disease. PMID- 1880848 TI - Spontaneous carotid dissection: duplex scanning in diagnosis and management. AB - The clinical, duplex, and angiographic findings in six patients with seven spontaneous extracranial carotid artery dissections are reported. Four dissections resulted in internal carotid artery occlusion. These patients complained of ipsilateral headache followed by contralateral hemiplegia. The other three dissections involved the common carotid artery and resulted in dual (one true and one false) lumens. Two of these dissections were asymptomatic. All dissections were treated nonoperatively with anticoagulant therapy. Neurologic deficits improved or disappeared in all symptomatic patients. On follow-up studies, one of the four internal carotid occlusions completely resolved with normalization of the duplex examination. All three dual lumen dissections remained patent on serial studies. Diagnostic duplex characteristics, both conclusive and supportive, of carotid dissections are described. Duplex scanning is shown to be accurate in diagnosing and ideally suited for serially following spontaneous carotid dissections. PMID- 1880849 TI - Hip disarticulation: factors affecting outcome. AB - Hip disarticulation, especially in patients with peripheral vascular disease, has been associated with high morbidity and mortality rates. This report describes patient characteristics that influence the clinical outcome of hip disarticulation. The medical records of all patients undergoing hip disarticulation from 1966 to 1989 were reviewed for surgical indication, perioperative wound complications, and postoperative deaths. Fifty-three patients underwent hip disarticulation for limb ischemia (10), infection (12), infection and ischemia (14), or tumor (17). The overall incidence of wound complications was 60%, and no significant differences were found among the groups. Prior above knee amputation and urgent/emergent operations were significantly associated with increased wound complications (p less than 0.05). The overall mortality rate was 21%, ranging from 0% (tumor) to 50% (ischemia) and differed significantly among the groups (p less than 0.02). Mortality was significantly associated with urgent/emergent operations (p less than 0.01). Age, diabetes mellitus, and previous inflow procedures did not influence mortality rates. The presence of limb ischemia influenced mortality rates to a greater extent than did infection, and a history of cardiac disease was statistically predictive of death. Wound complications frequently accompanied hip disarticulation, regardless of operative indication, and were significantly increased by urgent/emergent operations and prior above-knee amputation. Hip disarticulation can be performed with low mortality rates in selected patients. Both limb ischemia and infection substantially increase operative mortality rates. PMID- 1880850 TI - Renal cell carcinoma with inferior vena caval involvement. AB - Renal cell carcinoma extends into the lumen of the inferior vena cava in approximately 4% of patients at the time of diagnosis. Surgical removal of the intracaval tumor thrombus with radical nephrectomy is the preferred treatment for this malignancy. From January 1977 to June 1990, 31 such patients were examined for combined problems of renal carcinoma and intracaval tumor extension. Twenty six of these patients underwent radical nephrectomy and vena caval thrombectomy. Ten patients had tumor thrombus confined to the infrahepatic vena cava, 11 had retrohepatic caval involvement, and 5 had extension to the level of the diaphragm or into the right atrium. Surgical approach was dictated by the level of caval involvement. Control of the suprahepatic vena cava plus temporary occlusion of hepatic arterial and portal venous inflow were necessary in some cases; cardiopulmonary bypass was required for transatrial removal of more extensive tumors. Five of the 26 patients had evidence before operation of distant metastatic disease; none of these survived beyond 12 months. The 5-year actuarial survival rate of the 21 patients without known preoperative metastatic disease was 57%. Complete surgical excision of all gross tumor appears to be critical for long-term survival in these patients. PMID- 1880851 TI - Restructuring general surgical residencies. PMID- 1880853 TI - Declining childhood immunization rates becoming cause for concern. PMID- 1880852 TI - Primary popliteal venous aneurysm with recurrent pulmonary emboli. PMID- 1880854 TI - Unique 'day hospital' offers bridge between hospitalization, return to independent living. PMID- 1880855 TI - Music not only has charms to soothe, but also to aid elderly in coping with various disabilities. PMID- 1880856 TI - Tissue bank expands facilities, efforts. PMID- 1880857 TI - Undifferentiated cell transplant techniques appear effective in treating leg ulcers, vitiligo. PMID- 1880858 TI - Implantable lung-assist device being tested on patients with acute respiratory failure. PMID- 1880859 TI - Space motion sickness, hearing loss, and bifocals meet their match in vestibular system's plasticity. PMID- 1880860 TI - Estrogen replacement therapy and risk of breast cancer. PMID- 1880861 TI - Estrogen and coronary heart disease in women. PMID- 1880862 TI - A meta-analysis of estrogen replacement and breast cancer. PMID- 1880863 TI - Braccio da gamba. PMID- 1880864 TI - Salty and bitter taste. PMID- 1880865 TI - Surgery, AIDS, and hepatitis B. PMID- 1880866 TI - Clinical and laboratory features of murine typhus in south Texas, 1980 through 1987. AB - OBJECTIVE: --The clinical and laboratory features of patients with murine typhus have not been extensively reviewed since 1946. We have updated these findings in patients from south Texas who were examined by modern clinical and laboratory methods from 1980 through 1987. DESIGN: --Patients were identified by serological methods in this case series, and clinical, epidemiologic, laboratory, and therapeutic data were compiled and analyzed. SETTING: --The majority of patients (77 of 80) were identified in a primary care community hospital setting; the remainder (3 of 80) were ambulatory hospital outpatients. PATIENTS: --From 1980 through 1987, a total of 345 patients were diagnosed with murine typhus; 90 of these patients were seen at four hospitals in south Texas; of these, 80 had clinical and laboratory data available for review. MAIN OUTCOME MEASURES: --The frequency of common clinical manifestations (eg, headache, fever, and rash) and laboratory findings (eg, leukocyte and platelet counts and serum chemistry abnormalities) of patients with infectious diseases was tabulated. Clinical severity was semiquantitatively assessed and was correlated with clinical, laboratory, and therapeutic results. RESULTS: --Most cases (69%) occurred from April through August. Rash occurred in 54%; the triad of fever, headache, and rash was observed in only 12.5% of patients when first examined by a physician; respiratory and gastrointestinal symptoms were also frequent. Multiple organ involvement was documented by frequent abnormal laboratory findings of the hematologic, respiratory, hepatic, and renal systems. Disease severity was related to older patient age, the presence of renal dysfunction, leukocytosis, and hypoalbuminemia, and previous therapy with sulfa antibiotics. CONCLUSIONS: - Infection by Rickettsia typhi causes a systemic illness with clinical and laboratory abnormalities not previously recognized or described. Early clinical diagnosis and treatment are needed to avoid undue morbidity and mortality. PMID- 1880867 TI - Resident work hours and working environment in otolaryngology. Analysis of daily activity and resident perception. AB - OBJECTIVE: --To analyze the working environment and work hours of a cohort of otolaryngology--head and neck surgery residents. DESIGN: --Environmental analysis questionnaire and a log of daily activities. SETTING: --Residents were on a clinical rotation system. PARTICIPANTS: --Fifty-nine residents from six programs, including three public and three private institutions, from geographically diverse regions of the country were involved in the study. Residents were equally distributed from their second year through their fifth year of postgraduate work. All eligible residents participated in and completed the study. INTERVENTION: - The environmental analysis survey was designed to elicit resident perception of different aspects of their working environment. The daily activity log required the resident to report on activities for each half-hour period for 7 consecutive days. RESULTS: --Residents were on call an average of 52.8 hours (2.2 days) and worked 79.4 hours per week. Seventy-five percent believed that the level of faculty supervision and the degree of resident responsibility was about right. Two major inefficiencies were the time involved in completion of paperwork and the lack of nonmedical support services. Thirty-one percent of the residents responded that fatigue resulted in substandard patient care 10% of the time. Forty-seven percent responded that their educational experience was substandard 25% of the time secondary to fatigue. Two thirds responded that the demands of residency training had a negative impact on their family and personal life. CONCLUSIONS: --Seventy percent of the otolaryngology--head and neck surgery residents surveyed at six institutions believe that an 80-hour workweek, including being on call every third night with no more than 24 hours of continuous work without sleep, approximates a reasonable, maximum work schedule. Residents working the longest hours expressed concern about rendering substandard care and developing negative attitudes toward patients. Noneducational inefficiencies were identified and solutions were proposed. Demands of residency training, even within guidelines established as reasonable, can have detrimental effects on residents' educational activities and personal life. PMID- 1880868 TI - Pathophysiology of upper airway closure during sleep. AB - While the upper airway normally remains patent during quiet breathing in wakefulness and sleep, patients with obstructive sleep apnea have repetitive periods of upper airway closure during sleep. The upper airway closures usually occur at various sites in the pharynx. The patency of the potentially collapsible pharynx during inspiration depends on the balance between subatmospheric pressure in the pharyngeal airway and airway dilating forces generated by pharyngeal muscles. The pressure required to collapse the upper airway in the absence of upper airway muscle activity, ie, closing pressure, is normally subatmospheric. In obstructive sleep apnea, positive pressures are required to maintain patency of the passive upper airway. The pathophysiologic mechanisms underlying upper airway closures during sleep form the basis for the treatment of obstructive sleep apnea. In general, these treatment modalities attempt to (1) raise the pharyngeal pressure above the closing pressure, (2) decrease the closing pressure, or (3) increase upper airway muscle activity. PMID- 1880869 TI - Standardized patient encounters. A method for teaching and evaluation. AB - The primary goal of medical education is to foster development of clinical competence in trainees at all levels. Variable clinical experience, inconsistent methods of instruction, and ambiguous evaluation criteria undermine this goal. Standardized patients, trained to consistently portray a wide variety of clinical cases, can help overcome many of these educational problems. This article describes the development and application of standardized patients throughout medical training at The University of Texas Medical Branch, Galveston, in the freshman interviewing course, the second-year physical diagnosis course, third year clerkships, a fourth-year final exercise, and residency training. Development of this program is discussed in the context of a broader literature in medical education, and investigation of variables affecting standardized patient and student performance is reported. Future directions for use of standardized patients in monitoring and promoting the development of clinical competence are discussed. PMID- 1880870 TI - The decedent affairs office. A unique centralized service. AB - The success of a centralized decedent affairs office depends on support by clinicians, the department chairman, and hospital administration. The benefits to the institution include improved public relations with a decedent's family, compliance with state and federal laws, increased organ donations, and better risk management programs. The only drawback of establishing such an office is the additional personnel necessary for 24-hour coverage. However, modifications in the functions and staffing levels of a decedent affairs office may be made, depending on the needs of individual institutions. We hypothesized that consent for autopsy would be easier to obtain and cause less emotional upheaval for family members if procedures were well established and specially trained individuals were involved in the process. With these ideas in mind, we established a decedent affairs office at The University of Texas Medical Branch in 1984. PMID- 1880871 TI - The University of Texas Medical Branch at Galveston. Origins and beginnings. PMID- 1880872 TI - Physicians and medical education. PMID- 1880873 TI - UTMB is 100 years old. Looking back and at the road ahead. PMID- 1880874 TI - Medicine's arsenal in battling 'dominant dozen,' other AIDS-associated opportunistic infections. PMID- 1880875 TI - From the Food and Drug Administration. PMID- 1880876 TI - From the Centers for Disease Control. Nosocomial transmission of multidrug resistant tuberculosis among HIV-infected persons--Florida and New York, 1988 1991. PMID- 1880877 TI - Ocular tuberculosis. PMID- 1880878 TI - A piece of my mind. Dr dad. PMID- 1880879 TI - Continuous emotional support during labor. PMID- 1880880 TI - The costs of doctoring, the distribution of physicians, and caring for the underinsured. PMID- 1880881 TI - Oral decontamination and ventilator-associated pneumonia. PMID- 1880882 TI - Substance use and abuse. PMID- 1880883 TI - The neonatal costs of maternal cocaine use. AB - OBJECTIVE: --To examine the added neonatal cost and length of hospital stay associated with fetal cocaine exposure. DESIGN: --All cocaine-exposed infants in the study population (n = 355) were compared with a random sample of unexposed infants (n = 199). Regression analysis was used to control for the independent effects of maternal age, smoking, alcohol consumption, prenatal care, race, gravidity, and sex of the infant. SETTING: --A large, public, inner-city hospital studied from 1985 to 1986. PATIENTS: --All infants were routinely tested for illicit substances, records were reviewed for maternal histories of substance abuse, and all known cocaine-exposed singleton infants were included. MAIN OUTCOME MEASURES: --Cost and length of stay until each infant was medically cleared for hospital discharge and cost and length of stay until each infant was actually discharged from the hospital. RESULTS: --Neonatal hospital costs until medically cleared for discharge were $5200 more for cocaine-exposed infants than for unexposed infants (a difference of $7957 vs $2757 [P = .003]). The costs of infants remaining in the nursery while awaiting home and social evaluation or foster care placement increased this difference by more than $3500 (P less than .0001). Compared with other forms of cocaine, fetal exposure to crack was associated with much larger cost increases ($6735 vs $1226). Exposure to other illicit substances in addition to cocaine was also associated with much larger cost increases ($8450 vs $1283). CONCLUSIONS: --At the national level, we estimate that these individual medical costs add up to about $500 million. The large magnitude of these costs indicates that effective treatment programs for maternal cocaine abusers could yield savings within their first year of operation. PMID- 1880884 TI - Evidence for major gene transmission of developmental dyslexia. AB - OBJECTIVE: --There is strong evidence that developmental dyslexia is both familial and heritable, but the mode of genetic transmission has remained unclear. In this article, we examine specific genetic hypotheses about the mode of transmission of developmental dyslexia by performing complex segregation analyses. DESIGN: --A family study method was applied, whereby the relatives of dyslexic probands were examined for dyslexia. The families studied represent four independently ascertained samples. SETTING: --The four samples of families were primarily from rural and suburban communities of Colorado, Washington State, and Iowa. PARTICIPANTS: --A total of 204 families and 1698 individuals in the four samples combined. MAIN OUTCOME MEASURES: --The complex segregation program, POINTER, was used to test competing genetic hypotheses of how a categorical trait (dyslexia) is transmitted in families. RESULTS: --The results were consistent with major locus transmission in three of four samples and with polygenic transmission in the fourth. In these three samples, the estimates of penetrance for the AA, Aa, and aa genotypes (where A is the abnormal allele) were, respectively, 1.000, 1.000, and 0.001 to 0.039 in males, and 0.560 to 1.000, 0.550 to 0.897, and 0.000 in females. The estimated gene frequency of the major locus was between 3% and 5%. CONCLUSIONS: --Sex-influenced, additive, or dominant transmission occurs in a significant proportion of dyslexic families. Other evidence indicates, however, that dyslexia is etiologically heterogeneous and that there is genetic heterogeneity even among families selected for apparent dominant transmission. Thus, while no single major locus may account for all of dyslexia, it is important to pursue potential major loci for dyslexia using linkage techniques. PMID- 1880885 TI - Group- vs home-based exercise training in healthy older men and women. A community-based clinical trial. AB - OBJECTIVE: --To determine the effectiveness of group- vs home-based exercise training of higher and lower intensities among healthy, sedentary older adults. DESIGN: --Year-long randomized, controlled trial comparing (1) higher-intensity group-based exercise training; (2) higher-intensity home-based exercise training; (3) lower-intensity home-based exercise training; or (4) assessment-only control. SETTING: --General community located in northern California. PARTICIPANTS: --One hundred sixty women and 197 men 50 to 65 years of age who were sedentary and free of cardiovascular disease. One out of nine persons contacted through a community random-digit-dial telephone survey and citywide promotion were randomized. INTERVENTIONS: --For higher-intensity exercise training, three 40-minute endurance training sessions per week were prescribed at 73% to 88% of peak treadmill heart rate. For lower-intensity exercise training, five 30-minute endurance training sessions per week were prescribed at 60% to 73% of peak treadmill heart rate. MAIN OUTCOME MEASURES: --Treadmill exercise test performance, exercise participation rates, and heart disease risk factors. RESULTS: --Compared with controls, subjects in all three exercise training conditions showed significant improvements in treadmill exercise test performance at 6 and 12 months (P less than .03). Lower-intensity exercise training achieved changes comparable with those of higher-intensity exercise training. Twelve-month exercise adherence rates were better for the two home-based exercise training conditions relative to the group-based exercise training condition (P less than .0005). There were no significant training-induced changes in lipid levels, weight, or blood pressure. CONCLUSIONS: --We conclude that (1) this community based exercise training program improved fitness but not heart disease risk factors among sedentary, healthy older adults; (2) home-based exercise was as effective as group exercise in producing these changes; (3) lower-intensity exercise training was as effective as higher-intensity exercise training in the home setting; and (4) the exercise programs were relatively safe. PMID- 1880886 TI - Ocular cicatricial pemphigoid occurring as a sequela of Stevens-Johnson syndrome. AB - Ocular cicatricial pemphigoid is a chronic scarring inflammation of the ocular mucosae that can lead to blindness. Although cicatricial pemphigoid has been classified clinically, histopathologically, and immunopathologically, no definite initiating factor or precipitating factor has been identified. In this report, we describe five cases of ocular cicatricial pemphigoid that developed following an acute episode of severe ocular inflammatory injury secondary to Stevens-Johnson syndrome. The time lag between the onset of Stevens-Johnson syndrome and cicatricial pemphigoid ranged from a few months to 31 years. All five patients had linear immune deposits characteristic of cicatricial pemphigoid along the basement membrane zone of mucosal biopsy specimens as detected by either direct immunofluorescence microscopy or direct immunoperoxidase staining. In two patients whose serum was tested, a Western blot assay taken of keratinocyte antigens that had undergone electrophoresis reacted with the serum and identified a 120-kd epidermal antigen detected by the IgG class antibodies. All five patients were treated with systemic immunosuppressive therapy for cicatricial pemphigoid, and we obtained objective responses. Severe ocular mucosal injury such as that which occurs in Stevens-Johnson syndrome may be a precipitating factor in the development of ocular cicatricial pemphigoid. PMID- 1880887 TI - The measles epidemic. The problems, barriers, and recommendations. The National Vaccine Advisory Committee. AB - The nation has experienced a marked increase in measles cases during 1989 and 1990. Almost one half of all cases have occurred in unvaccinated preschool children, mostly minorities. The principal cause for the epidemic is failure to provide vaccine to vulnerable children on schedule. Major reasons for the low vaccine coverage exist within the health care system itself, which creates barriers to obtaining immunization and fails to take advantage of many opportunities to provide vaccines to children. Ideally, immunizations should be given as part of a comprehensive child health care program. However, immunization cannot await the development of such an ideal system. Essential changes can and should be made now. Specific recommendations include improved availability of immunization; improved management of immunization services; improved capacity to measure childhood immunization status; implementation of the two-dose measles vaccine strategy; and laboratory, epidemiologic, and operational studies to further define the determinants of decreased vaccine coverage and to develop new combinations of vaccines that can be administered earlier in life. The measles epidemic may be a warning flag of problems with our system of primary health care. PMID- 1880888 TI - Surreptitious self-administration of epinephrine resulting in 'pheochromocytoma'. PMID- 1880889 TI - Mandatory treatment for drug use during pregnancy. PMID- 1880890 TI - The trials of Medicare physician payment reform. PMID- 1880891 TI - Whom can we trust? PMID- 1880892 TI - Drugs, alcohol, pregnancy, and the neonate. Pay now or pay later. PMID- 1880893 TI - From the Office of the General Counsel. Occurrence vs claims-made medical professional liability insurance policies. Fundamental differences in the concept of coverage. PMID- 1880894 TI - Thyroid-stimulating hormone: reference range validity. PMID- 1880895 TI - Thyroxine: treatment for headache? PMID- 1880896 TI - Hemodynamic mechanism of the elevation in blood pressure following the improvement of anemia with recombinant human erythropoietin. AB - Following the administration of recombinant human erythropoietin (rHuEPO) to 18 patients undergoing hemodialysis, the hematocrit (Ht) increased from 19.7 +/- 1.8 to 31.0 +/- 2.0%. The incidence of hypertension according to the criteria of WHO was 11.1%. The systolic blood pressure (SBP) increased significantly from 120 +/- 21 to 129 +/- 26 mmHg (p less than 0.01) and diastolic blood pressure (DBP) increased from 67 +/- 14 to 73 +/- 12 mmHg (p less than 0.05). The cardiac index (CI) decreased significantly from 4.07 +/- 1.13 to 3.56 +/- 0.88 L/min/m2 (p less than 0.05). Total peripheral resistance index (TPRI) and blood volume (BV) increased significantly from 1,725 +/- 406 to 2,170 +/- 643 dynes/sec/cm-5/m2 (p less than 0.001) and from 78.9 +/- 11.2 to 87.8 +/- 14.8 ml/kg (p less than 0.005) respectively. Pulse rate (PR) decreased significantly from 73.0 +/- 10.7 to 65.9 +/- 7.8 beats/min (p less than 0.01). Patients who developed a blood pressure (BP) elevation of 10% or more for the mean blood pressure (MBP) showed a slight and insignificant decrease in CI from 3.65 +/- 1.12 to 3.49 +/- 1.06 L/min/m2, which clearly contrasted to that in another group of patients who showed a reduced increase in MBP and a significant reduction in CI from 4.50 +/- 1.03 to 3.63 +/- 0.72 L/min/m2 (p less than 0.05). Stroke volume index (SVI) was unchanged in both groups but PR decrease significantly in the latter group. A significant increase in TPRI or BV was observed equally in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880897 TI - Increase in left ventricular chamber stiffness in patients with non-insulin dependent diabetes mellitus. AB - Indices of left ventricular ejection and diastolic filling were measured by cineventriculography in 11 patients with non-insulin dependent diabetes mellitus without significant coronary stenosis and 11 control subjects without diabetes mellitus. Indices of left ventricular ejection, such as ejection fraction and peak ejection rate, were the same in the two groups. The left ventricular end diastolic volume index and the rapid filling volume index were significantly smaller, the peak filling rate was lower, the left ventricular end-diastolic pressure was higher and the modulus of left ventricular chamber stiffness was larger in the diabetic patients than in the control subjects. These results indicate that left ventricular chamber stiffness is increased in patients with non-insulin dependent diabetes mellitus. PMID- 1880898 TI - Acute and chronic stability of atrial screw-in leads. AB - The purpose of this study was to evaluate the acute and chronic stability of the atrial screw-in lead. In this study, we used CPI model 4165, 4166, and 4266 porous tip screw-in leads in 32 patients (12 for AAI pacing and 20 for DDD pacing). All of these leads were fixed to the free wall of the right atrium and used as the unipolar type. Acute voltage and current thresholds, lead impedance, P-wave amplitude, and chronic threshold were measured. Early and late complications were also investigated. The average acute stimulation thresholds at 0.6 msec pulse width were 0.82 +/- 0.43 V and 1.1 +/- 0.6 mA. Mean lead impedance was 627.2 +/- 83.1 ohms, and mean P wave amplitude was 3.1 +/- 1.1 mV. After an average follow-up period of 32 months (range: 2-72 months), we found the results of the chronic threshold study to be satisfactory. The thresholds were usually below 0.1 msec pulse width with the nominally programmed pacemaker output. Only one patient required a higher output due to an increased threshold. With regard to complications, neither lead dislodgment nor cardiac perforation was observed. In conclusion, acute and chronic thresholds were satisfactory and no serious complications occurred. Therefore the atrial screw-in lead has long-term reliability and stability. PMID- 1880899 TI - Clinical experience in patients with implantable cardioverter defibrillators. AB - Forty patients (36 men and 4 women) with life-threatening arrhythmia received an implantable cardioverter defibrillator (ICD). Mean age was 63 years (range, 46 to 80 years). All patients had structural heart disease, with coronary artery disease in 32 patients, idiopathic cardiomyopathy in 7 patients, and hypertensive heart disease in 1 patient. Mean left ventricular ejection fraction was 29 +/- 13%. The clinical arrhythmia was out-of-hospital cardiac arrest in 14 patients (35%), symptomatic sustained ventricular tachycardia in 21 patients (53%), and episodes of syncope without documented spontaneous ventricular arrhythmia but ventricular tachycardia that was easily provoked at the time of electrophysiologic testing in 5 patients (13%). Sustained ventricular tachycardia was induced in 37 patients (93%) at basic electrophysiologic testing. The average number of drug failures was 2.9 +/- 1.4 per patient. One patient (2.5%) died perioperatively because of intractable ventricular tachycardia and ventricular fibrillation. During a median follow-up period of 5.5 months (range 2-21 months) 2 sudden deaths occurred. No patient had a serious complication during the follow up period. Ten patients (25%) received antiarrhythmic drugs to suppress spontaneous ventricular tachycardia. Appropriate shock treatment was received by 18 patients (45%), and inappropriate shock treatment was received by 2 patients (5%). Several issues regarding use of the ICD must be considered, but the device seems to be useful, and it is associated with an acceptable rate of complications and good long-term success at the present time. PMID- 1880900 TI - Comparative study of five preoperative methods for the localization of accessory pathways in the Wolff-Parkinson-White syndrome. AB - One hundred and thirty-four cases of Wolff-Parkinson-White syndrome were studied to evaluate the relative usefulness of electrocardiography (ECG), electrophysiological studies (EPS), body surface mapping (BSM), gated blood-pool phase analysis (nuclear studies), and vectorcardiography (VCG) in the localization of the accessory pathway (ACP). In comparison with the final localization verified by intraoperative studies, 93.4% in 8-region ACP localization (97.7% in 4-region ACP localization) could be correctly localized by ECG using our criteria, 83.9% (86.8%) by EPS, 82.6% (95.8%) by BSM, 78.8% (87.7%) by nuclear studies, and 67.3% (78.0%) by VCG. It was concluded that: (a) ACP can be localized preoperatively with considerable accuracy by using our simple ECG criteria. (b) The EPS method has some limitation, especially with respect to 8 region ACP localization. (c) Our observation showed no evidence that BSM, VCG, or nuclear studies were superior to ECG in ACP localization. (d) Among the 5 methods studied, ECG and EPS appear to be the appropriate procedures for preoperative ACP identification. PMID- 1880901 TI - Unruptured aneurysm of the right coronary cusp. AB - A 44-year-old man with an unruptured aneurysm originating from the right coronary cusp is reported. The patient was asymptomatic and a heart murmur and abnormal electrocardiogram were discovered incidentally. Echocardiography and aortography showed an unruptured aneurysm of the right coronary cusp. Surgical correction was successful using a Dacron patch and aneurysmal wall. PMID- 1880902 TI - Progressive restrictive cardiomyopathy--a case report. AB - We present a case of restrictive cardiomyopathy which progressed over a 10 month period. A 69-year-old female was admitted because of acute inferior myocardial infarction; hemodynamically, she was in Forrester subset I. Cardiac catheterization performed 4 weeks post-infarction showed markedly increased left ventricular end-diastolic and pulmonary wedge pressures. Left ventricular ejection fraction was 66% with postero-basal akinesis and minimal mitral regurgitation. The right coronary artery was completely occluded with good collateral circulation from the intact left coronary artery. Doppler echocardiography 4 weeks post-infarction showed pseudo-normalization of the A/E ratio of peak mitral flow velocity in atrial systole (A) to peak mitral flow velocity in early diastole (E). Preload reduction by nitroglycerin increased the A wave. Ten months post-infarction, the patient was re-admitted due to congestive heart failure. The A/E ratio was unchanged, however the A wave no longer increased after the same dose of nitroglycerin. We have hypothesized that dehydration and/or the vigorous use of a nitrate, in the acute phase of myocardial infarction, masked an underlying restrictive cardiomyopathy which progressed in the 10 months post-infarction. PMID- 1880903 TI - Remnant valve of inferior vena cava dislodged by Swan-Ganz catheter. AB - We experienced a rare case of a patient with acute myocardial infarction. It was rare in that a piece of tissue, probably a remnant valve of the inferior vena cava in the right atrium, was dislodged by the Swan-Ganz catheter during a right heart catheterization study in the chronic phase of the disease. As far as we know, no other such case has been reported. Such remnants are considered to be present in 2 to 3% of the general population. Therefore, it is necessary to determine the presence or absence of a remnant before cardiac catheterization and to modify the procedure, such as by changing the catheter's approach, when a remnant is present. PMID- 1880904 TI - Transcoronary chemical ablation of atrioventricular node for the treatment of paroxysmal supraventricular tachycardia--a case report. AB - We applied transcoronary chemical ablation of the atrioventricular (AV) node to a patient with uncontrollable paroxysmal supraventricular tachycardia (PSVT). Through an angioplasty dilatation catheter. 99% ethanol at a dose of 1.0 ml was selectively infused into the AV nodal artery. Complete AV block with junctional escape rhythm occurred. Two weeks later, the treadmill exercise test was performed according to a modified Bruce protocol. The patient tolerated for 12 min, and the heart rate increased to 85 beats/min. His bundle electrocardiogram showed that the AV block resulted from atrio-Hisian block. Neither atrial nor ventricular extrastimulus could induce the tachycardia. It appeared that chemical ablation was a good method for controlling medically resistant PSVT. Elevation of serum creatine kinase was observed when ethanol overflowed during the ablation procedure. Occlusion of branches of the AV artery and mild hypokinesis in the inferobasal wall of the left ventricle were seen. PMID- 1880905 TI - Ischemic myocardial mitochondrial function and ultrastructural change--influence of regional myocardial blood flow. AB - Myocardial blood flow (MBF), tissue ATP content, mitochondrial respiratory function and mitochondrial ultrastructure were examined in 62 adult mongrel dogs weighing 6-14 kg in which acute myocardial ischemia had been produced under anesthesia. The left anterior descending coronary artery was dissected free for ligation before the first diagonal branch. MBF was measured before coronary ligation and 60 min following ligation. Then, samples of myocardium were taken and subjected to tissue ATP content assay, mitochondrial respiratory function measurement respiratory control index (RCI) and rate of oxygen consumption in state III (QO2III); and electron microscopic examination. Mitochondrial morphologic injury was evaluated quantitatively according to Schaper's criteria. MBF was significantly correlated with tissue ATP content, mitochondrial respiratory function and mitochondrial ultrastructural change. When MBF was less than 20 ml/min/100g, tissue ATP content (1.86 +/- 1.21 mumol/g wet weight) and mitochondrial respiratory function (RCI 2.51 +/- 0.59) were significantly lower than in the non-ischemic area (ATP 4.52 +/- 1.11, RCI 3.82 +/- 0.37), and mitochondrial ultrastructural injury had deteriorated significantly at an MBF below 40 ml/min/100 g. In conclusion, our findings show that when MBF is reduced, mitochondrial ultrastructural changes precede the depression in mitochondrial oxidative phosphorylation. PMID- 1880906 TI - The influence of left ventricular relaxation in determination of the intensity of the aortic component of the second heart sound. AB - In a study of the aortic component of the second heart sound (A2) intensity, using 10 dogs, miniature cardiac accelerometers were attached to the exposed left ventricle (LV) at the apex, and to the surface of proximal aorta, to obtain LV and aortic surface acceleration. Manometer tipped catheters were used to detect aortic systolic pressure and diastolic pressure and time constant of left ventricular pressure fall "T". Drugs (Nitroprusside, Dobutamine and Methoxamine) altered aortic pressure, LV contraction and LV relaxation. When T was +/- 35% of control, the aortic systolic pressure and diastolic pressure were good predictors of A2 intensity. When LV relaxation was impaired, increasing T greater than 135% of control, the A2 intensity for any given aortic pressure was reduced. When relaxation was hyperactive, decreasing T less than 65% of control, A2 intensity was increased. Aortic pressure/T which assessed both aortic pressure and relaxation ability, is a better determinant of A2 intensity than aortic systolic pressure or aortic diastolic pressure alone. PMID- 1880907 TI - [Cefodizime]. PMID- 1880908 TI - Photochemical production of anthracycline antibiotic oxaunomycin from precursor metabolite D788-1. PMID- 1880909 TI - Anthracycline antibiotic 2-hydroxyaclacinomycins. I. 2-Hydroxyaclacinomycin producing recombinant obtained from aclacinomycin-blocked mutants of Streptomyces galilaeus by a technique of protoplast fusion. AB - The technique of protoplast fusion which optimized prototrophic recombination in aclacinomycin-producing Streptomyces galilaeus was studied and applied to the construction of new anthracycline analog-producing recombinant upon genetic cross of two specific mutants blocked in aclacinomycin biosynthesis. Thus, 2 hydroxyaclacinomycin-producing recombinant was obtained by the protoplast fusion. PMID- 1880910 TI - Anthracycline antibiotic 2-hydroxyaclacinomycins. II. Production of 2 hydroxyaclacinomycins A and B by a new recombinant strain and their antitumor activities. AB - Anthracycline antibiotics 2-hydroxyaclacinomycins A and B were isolated and purified from the culture broth of a recombinant strain which was produced by protoplast fusion of two aclacinomycin-blocked mutants. 2-Hydroxyaclacinomycin B is a new compound for which chemical structure and the biological activity in vitro were determined. 2-Hydroxyaclacinomycins had a stronger antitumor activity against murine leukemic L1210 cells in mice than the parent antibiotic aclacinomycins. PMID- 1880911 TI - [An evaluation of combination antibiotic therapy in infections with hematological disorders. Hyogo Cooperative Study Group of Infectious Diseases Complicating Hematological Disorders]. AB - A clinical study was undertaken to determine the effects of combination antibiotic therapy in 104 patients with infections associated with hematological disorders. All patients were treated with sulbactam/cefoperazone (SBT/CPZ) plus an aminoglycoside as an empiric therapy for fever. The overall efficacy rate of the therapy was 63.5%. Efficacy rates were 61.2% and 71.9% when initial neutrophil counts were less than 500/mm3 and over 500/mm3, respectively. No significant difference was found between the cases in which initially used antibiotics were continued (efficacy rate 62.5%) and those in which antibiotics were switched during the course of therapy (65.6%). Antibiotic therapy with SBT/CPZ plus an aminoglycoside provides adequate antibiotic coverage against infections associated with hematological disorders. This combination was highly effective even in the neutropenic periods of febrile patients. PMID- 1880912 TI - [Clinical features and evaluation of initial antibiotic treatment in 125 cases with purulent meningitis in infancy and childhood]. AB - A survey of purulent meningitis in infancy and childhood from 1980 through 1986 was made by sending questionnaires to 32 pediatric institutions in Aichi, Gifu and Shizuoka prefectures. Case cards of 125 patients were collected and analyzed. The results are summarized as follows: 1. The sex ratio (male/female) was 1.78. The age distribution for all patients was as follows: younger than 1 month, 24.8%; 1-12 months, 32.8%; 1 year, 19.2%; 2-5 years, 16.0%; older than 6 years, 7.2%. Nearly 3/4 of all purulent meningitis cases occurred in infancy. 2. The isolation rate of causative organisms was 71.2%. The 4 major causative organisms were Haemophilus sp. (28 cases), Streptococcus pneumoniae (14 cases), Streptococcus agalactiae (13 cases), and Escherichia coli (12 cases). Haemophilus sp. was dominant in patients over 3 months of age, and S. pneumoniae was noted in all age groups. The latter 2 were dominant under 3 months of age. 3. The outcome of 125 cases was as follows: cured, 73 cases (58.4%); improved, 26 cases (20.8%); dead, 15 cases (12.0%); unknown, 11 cases (8.8%). As to the outcome by age, the mortality of infants within 1 month old was the highest, 29.0%, and then decreased with increasing age. As to the outcome by causative organisms, Haemophilus sp. and E. coli were associated with good outcome, whereas S. pneumoniae and S. agalactiae with poor outcome. 4. Among several antibiotics, ampicillin was the most frequently used in 94 cases, followed by cefotaxime in 50 cases. 5. As to the initial antibiotic treatment, 51 cases were treated with penicillins (PCs) (including PCs + aminoglycosides (AGs], 9 cases with cephalosporins group I, II, IV, (CEPs I, II, IV) (including CEPs I, II, IV + AGs), 25 cases with CEPs V (including CEPs V + AGs) and 31 cases with CEPs V + PCs (including CEPs V + PCs + AGs). No significant differences were observed in the outcome among these initial treatment group. 6. Compared with the initial treatments of CEPs V or CEPs V + PCs groups, other antibiotics were used more frequently in those of PCs + AGs and CEPs I, II, IV groups. In the light of this analysis, the initial treatments of purulent meningitis with PCs + AGs or CEPs I, II, IV were not so effective as those with CEPs V or CEPs V + PCs. PMID- 1880913 TI - [Treatment of severe infections in hematologic malignancies with piperacillin sodium]. AB - Combination antibiotic therapies using piperacillin (PIPC) were evaluated in 60 episodes of severe infections in 38 neutropenic patients with hematologic malignancies. 1. The overall efficacy rate was 46.7%. Efficacy rates were 30% in patients with pneumonia, 60% in patients with sepsis and 50% in patients with suspected sepsis in which causative organisms were not identified. 2. Eradication rates were 44.4% for Gram-negative bacilli, 50% for Pseudomonas aeruginosa and 22.2% for Gram-positive cocci. 3. Efficacy rates were 33.3% in patients with initial count of neutrophil less than 100/microliters, 60% in patients with those 100 to 500/microliters and 66.7% in patients with those higher than 500/microliters. Initial neutrophil counts correlated well with efficacies of PIPC on severe infection in patients with hematologic malignancies. 4. Mild increases of transaminase were observed in 2 cases. From these results it is concluded that PIPC is one of the most important antibiotics in the treatment of severe infections in neutropenic patients with hematologic malignancies. PMID- 1880914 TI - [Clinical effect of miconazole gel against upper digestive tract mycosis]. AB - A total of 43 patients, comprising 41 patients with oral candidiasis and 2 with esophageal candidiasis, were treated with miconazole (MCZ) gel to assess its efficacy and safety in treating upper digestive tract mycosis. The efficacy of the drug was evaluable in 33 of them, consisting of 32 patients with oral candidiasis and 1 with esophageal candidiasis. The clinical efficacy rate of the drug against oral candidiasis was 87.5% (28/32 patients), and the clinical response was good in the 1 evaluable patient with esophageal candidiasis. The safety of the drug was assessed in 40 patients. In 3 (7.5%) of them, nausea occurred as an adverse event, but was not particularly serious in any of them. No abnormal laboratory test values caused by the drug were observed. The results suggested that MCZ gel would be a very useful drug in treating oral and esophageal candidiasis. PMID- 1880915 TI - [Clinical effect of the combined use of aztreonam, amikacin and clindamycin in infectious disease in obstetrics and gynecology]. AB - Clinical effects of combined use of aztreonam (AZT), amikacin (AMK) and clindamycin (CLDM) in 46 cases with infectious diseases in obstetrics and gynecology were retrospectively studied in 2 groups, and the following results were obtained. 1. No significant difference in efficacy rates was noted between AZT plus CLDM treated group (n = 25) and AMK plus CLDM treated group (n = 21) (96.0% vs. 95.2%), while rate of excellent efficacy was slightly higher in AZT plus CLDM group than AMK plus CLDM group (24.0% vs. 14.3%). 2. No significant difference in bacteriological clinical effects was also noted between the 2 groups, while bacteriological eradication rate was higher in the AZT plus CLDM group than in the other group (76.2% vs. 50.0%), and the difference was particularly clear in the eradication rates of aerobic, Gram-negative bacteria (88.9% vs. 30.0%). 3. Subjective and objective side effects, and abnormalities of clinical test results were not found in either group. PMID- 1880916 TI - [A study of the absorption and excretion of fosfomycin sodium in children]. AB - Fosfomycin sodium (FOM-Na, Forocyle-S) was administered at 25 mg/kg or 50 mg/kg to 15 children between the ages of 3 and 15 through intravenous injection or through 1 hour intravenous drip infusion, and concentrations in blood serum and excretion through urine were examined and a pharmacokinetic analysis was carried out using the one-compartment model. 1. Average concentrations in the blood serum after injections with 25 mg/kg and 50 mg/kg were 55.3 +/- 6.3 micrograms/ml and 118.8 +/- 31.1 micrograms/kg 30 minutes after injection, respectively, and their half-lives were 1.04 +/- 0.15 hours and 0.98 +/- 0.17 hours, respectively. Six hours after injection, the levels were 2.7 +/- 1.6 micrograms/kg and 6.2 +/- 5.5 micrograms/kg, respectively. With 1 hour intravenous drip infusion of 25 mg/kg and 50 mg/kg, average concentrations the blood serum were 34.2 +/- 14.9 micrograms/ml and 89.7 +/- 6.7 micrograms/ml, respectively, and their half-lives were 0.87 +/- 0.24 hour and 0.69 +/- 0.10 hour, respectively. Six hours after the administration, the levels were 2.7 +/- 1.8 micrograms/ml and 6.7 +/- 0.8 micrograms/ml. There was a clear dose response in the concentration levels in the blood in those given the drug at 25 mg/kg and 50 mg/kg in either method of administration. 2. Average levels in urine after injection of 25 mg/kg and 50 mg/kg were 5,778 +/- 2,257 micrograms/ml and 6,268 +/- 3,329 micrograms/ml 0-2 hours after administration, respectively, and average levels at 4-6 hours were 701 +/- 765 micrograms/ml and 1,588 +/- 1,324 micrograms/ml, respectively. Average excretion, rates into the urine were 72.8 +/- 11.0 and 73.9 +/- 11.1%, respectively. In case of 1 hour drips infusion of 25 mg/kg and 50 mg/kg, average concentrations in the urine 0-2 hours after administration were 3,570 +/- 1,540 micrograms/ml and 11,800 micrograms/ml, respectively, and averages for 4-6 hours were 211 +/- 124 micrograms/ml and 1,300 micrograms/ml. Average rates of excretion into the urine for the first group was 57.9 +/- 16.3% and the second group was 78.4%. Clear dose response was observed in changes of drug concentration levels in the urine with 25 mg/kg and 50 mg/kg doses through either administration method, and in terms of excretion into the urine, no noticeable differences were observed between the different amounts administered or different administration methods.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1880917 TI - [Susceptibility to miconazole (base) of isolates from the oral cavity and esophagus of patients with mycosis]. AB - An antifungal agent of the imidazole class, miconazole (MCZ) (base), was investigated for its in vitro antifungal activities against isolates from the oral cavity and esophagus of patients with mycosis, and the following findings were obtained: 1. Those yeast-like fungi which were presumed to be the causative agents were isolated from the oral cavity and esophagus of patients with mycosis, and identified. Candida albicans was the most frequently occurring species, accounting for 71.4% of all the isolates. Less frequently, several other Candida species, such as Candida krusei, Candida tropicalis, Candida lusitaniae and Candida lipolytica were also isolated mostly from patients with polymicrobial infections. 2. The MICs of MCZ against the isolates of Candida species which were obtained from materials from patients with oral and esophageal candidiasis as the presumable causative agent distributed through such a wide range as less than or equal to 0.04 to 20 micrograms/ml, and susceptibilities of these isolates to MCZ proved to be no less than those to amphotericin B, which was used as the control drug. The results suggest that an appropriate preparation of MCZ (base) will be effective in treating mycosis of the oral cavity and esophagus. PMID- 1880918 TI - [New antimicrobial agent series XXXVII: potassium clavulanate/Ticarcillin sodium]. PMID- 1880919 TI - [Bacteriological and clinical studies of cefodizime in pediatrics]. AB - Bacteriological and clinical studies on cefodizime (CDZM, THR-221), a new cephem developed by Hoechst AG and Roussel Uclaf, were carried out and the results are summarized below: 1. Against Gram-positive bacteria, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae, antibacterial activities of CDZM were similar to those of cefotaxime (CTX), cefazolin, cefotiam and piperacillin. Against Escherichia coli, Klebsiella pneumoniae and Serratia sp., antibacterial activities of CDZM were similar to that of CTX, and superior to those of other tested antibiotics. Especially against Haemophilus influenzae and Branhamella catarrhalis, it showed an excellent antibacterial activity. 2. Although the clinical efficacy was poor in 1 patient with sepsis caused by Salmonella marcescens and in another with cervical lymphadenitis, in 5 patients with upper respiratory tract infection, 4 patients with bronchitis, 6 patients with bronchopneumonia, 18 patients with pneumonia, 5 patients with urinary tract infection and 1 patient with enteritis, the clinical efficacy was excellent or good and the efficacy rate was 95.1% (39/41) including excellent efficacies in 25 cases. 3. Bacteriologically, all identified causative bacteria were eradicated except for 1 case of Salmonella sp., thus the eradication rate was 97.4% (38/39). Especially S. pneumoniae in 10 cases, H. influenzae in 12 cases and B. catarrhalis in 3 cases were eradicated totally. 4. Adverse reactions were studied in 46 cases, and digestive symptoms were observed in 9 cases (diarrhea 5 cases, loose stools 4 cases). Eruption and vascular pain were observed in 1 case each. As digestive symptoms in 9 cases were mild, the treatment were not suspended. In laboratory test values, elevation of GOT, elevation of GPT, elevation of bilirubin, and eosinophilia were observed in 1 case each. Influences on blood coagulation parameters were studied. No change was observed between the beginning and the end of the treatment. From above results, we have concluded that CDZM is a useful and safe antibiotic in pediatrics, administered at a daily dose of 20 mg/kg divided into 3 or 4 doses and administered intravenously. PMID- 1880920 TI - [Influence of cefodizime on intestinal bacterial flora]. AB - Effects of cefodizime (CDZM), a new injectable cephem antibiotic, on the intestinal bacterial flora were studied in tetra-contaminated mice and in pediatric patients. CDZM was intramuscularly administered at a dose of 100 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organisms: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. For 3 species except E. faecalis, bacterial populations in feces were markedly reduced after the start of the treatment. Subjects in the pediatric study were 5 children with bacterial infections (4 boys and 1 girl) at ages from 7 months to 9 years 6 months and with their body weights ranging from 7.6 kg to 51.1 kg. CDZM was intravenously administered at a dose of 9.7 mg/kg to 23.0 mg/kg 4 times a day for 5 to 15 days. Although some variations in the fecal bacterial flora were noticed among these subjects during the treatment, populations of main aerobes and anaerobes such as Enterobacteriaceae, Enterococcus, Bacteroides, Bifidobacterium and Eubacterium decreased markedly in most cases. Glucose non-fermenting Gram-negative rods and fungi tended to increase during or after the administration of CDZM, and they were the most predominant species in some cases. Although these changes tended to return to predosing states after the cessation of the treatment with CDZM, attention must be paid to possible occurrences of diarrhea, superinfection or bleeding tendency when treatment with the drug is continued for long periods of time. Fecal concentrations of CDZM considered to be closely related to the changes of the intestinal bacterial flora showed pretty high values in all cases. PMID- 1880921 TI - [Pharmacokinetic and clinical evaluation of cefpirome in the pediatric field]. AB - Pharmacokinetic and clinical evaluations of cefpirome (CPR), a newly developed cephalosporin, were performed in the field of pediatrics. The results are summarized as follows. 1. Peak serum concentrations of CPR after a dose of 20 mg/kg via 30 minutes and that via 60 minutes intravenous drip infusion and a dose of 40 mg/kg via 60 minutes intravenous drip infusion were 80.8, 63.7 and 128.8 micrograms/ml, respectively, with half-lives being 1.41, 1.28 and 1.79 hours, respectively. Urinary excretion rates for CPR in the first 6 hours after administration ranged 66.7-77.1%. 2. The clinical efficacy rate in pediatric infections obtained at daily dose levels ranging 55.6-166.7 mg/kg was 95.7%. 3. The eradication rate for 22 strains identified in the study was 95.5%. 4. Side effects were found in 2 cases of diarrhea. The abnormal laboratory test results were observed in 5 cases with 7 test items (increased number of platelets; 2 cases, increased activity of GOT; 2 cases and increased activity of GPT; 1 case). According to these results, CPR was considered to be a useful antimicrobial agent in pediatric infections. PMID- 1880922 TI - [Bacteriological, pharmacokinetic and clinical studies of cefpirome in the field of pediatrics]. AB - Bacteriological, pharmacokinetic and clinical studies on cefpirome (CPR, HR 810), a new cephem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized below. 1. Antibacterial activities of CPR against clinically isolated strains of Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae and Haemophilus parainfluenzae were superior to those of ceftazidime. 2. Plasma concentrations and urinary excretion rates after intravenous bolus injection of CPR at doses of 10, 20 and 40 mg/kg for 5 minutes in 2 cases each were determined. Mean peak plasma concentrations of CPR at these dose levels were 33.9, 62.9 and 96.0 micrograms/ml at 15 minutes with plasma half-lives of 1.58, 1.69, and 2.13 hours, respectively. Mean cumulative urinary excretion rates in the first 8 hours after administration were 51.2, 78.0 and 74.9%, respectively. 3. Ten patients with bacterial infections (pneumonia 5 cases, urinary tract infection 5 cases) were treated with CPR at a daily dose of 16-79 mg/kg/day. The overall clinical efficacy and bacteriological eradication rates were both 100%. 4. No adverse reactions were observed except in 1 case of mild pain in blood vessels. Abnormal laboratory test results were also mild, slight elevation of GOT, GPT and thrombocytosis in 1 case and eosinophilia in 1 case. PMID- 1880923 TI - [Clinical evaluation of cefpirome in children]. AB - Cefpirome (CPR, HR 810) was clinically evaluated for its efficacy and safety in 11 patients with ages from 4 months to 11 years with bacterial infection. The results obtained are summarized as follows. 1. CPR was administered to 6 patients with bronchopneumonia, a patient with pneumonia, a patient with tonsillitis, 2 patients with acute pharyngitis and a patient with suppurative parotitis at daily dosage levels ranging 55.5-91.7 mg/kg, divided into 3 using intravenous bolus injection or 30 minutes drip infusion. Clinical responses of the 11 patients were as follows: excellent; 8 patients, good; 2 patients, poor; 1 patient, hence the efficacy rate was 90.9%. 2. Neither clinical adverse reaction nor abnormal laboratory test value was observed except slight elevation of GOT and GPT in a patient and leukopenia in another. 3. MICs of CPR against 18 beta-lactamase producing strains isolated from patients were as follows. MIC against a strain of Staphylococcus aureus was 1.56 micrograms/ml, MICs against 3 strains of Klebsiella pneumoniae were less than 0.025 microgram/ml, those against 3 out of 5 strains of Enterobacter cloacae were less than 0.025 microgram/ml and those against the remaining 2 strains were 0.05 and 0.20 micrograms/ml. MICs against 2 out of 3 strains Acinetobacter lwoffi were 1.56 micrograms/ml, and that of the remaining 1 strain was 0.39 microgram/ml. MICs against 2 strains of Pseudomonas cepacia were 1.56 micrograms/ml. MICs against a strain of Pseudomonas putida and a strain of Citrobacter diversus were 0.78 and less than 0.025 microgram/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880924 TI - [Laboratory and clinical studies of cefpirome in pediatric field]. AB - We have carried out laboratory and clinical studies on cefpirome (CPR, HR 810). The results are summarized as follows. CPR was given by 30-minute drip infusion to 3 children at a single dose of 20 mg/kg. After the 30-minute drip infusion, the mean peak serum level of CPR was 65.7 +/- 2.2 micrograms/ml at the end of infusion, and the mean half-life was 1.49 +/- 0.046 hours. The mean urinary excretion rate of CPR was 57.0 +/- 25.8% in the first 8 hours after the 30-minute drip infusion of 20 mg/kg. Treatment with CPR was made in 9 cases of pediatric bacterial infections; 1 case each of tonsillitis, pharyngitis, and bronchopneumonia, 4 cases of pneumonia, 2 cases of urinary tract infection. Results obtained were excellent in 6 cases, good in 3 cases. No significant side effects due to the drug were observed except one case of elevated GOT and GPT, and 3 cases of eosinophilia. PMID- 1880925 TI - [Clinical evaluation of cefpirome in pediatric field]. AB - Cefpirome (CPR), a new synthetic cephalosporin antibiotic, was administered to 10 patients with infectious diseases. The patients included 5 boys and 5 girls from 1 month to 5 years of age. They were given the drug intravenously at dosages ranging 53-100 mg/kg/day for 4 to 10 days. Clinical efficacy was evaluated in 9 patients: excellent in 2 patients, good in 6 patients and fair in 1 patient. The overall efficacy rate was 88.9%. No adverse effects were observed except in one patient who showed a slight increase of serum GOT and GPT. PMID- 1880926 TI - [Clinical studies on cefpirome in pediatrics]. AB - Cefpirome (CPR, HR 810) was given intravenously to 10 children with acute bacterial infections including 8 with acute pneumonia, 1 each with acute pleuritis and urinary tract infections. Good to excellent clinical responses were obtained in all of the 10 patients and bacterial eradication were obtained for all 8 strains found in these cases. Slight elevation of GOT, GPT and eosinophilia were observed in 1 case each. From the above clinical results, it appears that CPR is a useful antibiotic for treatment of pediatric patients with various bacterial infections. PMID- 1880927 TI - [Clinical evaluation of cefpirome in pediatrics and a study on the penetration into cerebrospinal fluid]. AB - Cefpirome (CPR, HR 810), a new cephem antibiotic, was investigated for its penetration into cerebrospinal fluid (CSF), and its clinical efficacy against bacterial infections. 1. CSF concentrations of CPR following intravenous injection was investigated in 2 patients with purulent meningitis. In one of them, the concentrations were 2.11 micrograms/ml and 1.31 micrograms/ml on 3 and 8 days, respectively, after start of administration. In the other patient, they were 24.2 micrograms/ml, and 1.35 micrograms/ml on 2 days and 7 days after administration, respectively. 2. Antibacterial activities of CPR against clinical isolates, Escherichia coli, Haemophilus influenzae, Staphylococcus aureus and Streptococcus pneumoniae, except those against Pseudomonas aeruginosa, were clearly superior to those of ceftazidime. 3. Clinical efficacies evaluated in 15 patients were "excellent" in 9, "good" in 5 and "unknown" in 1. The overall efficacy rate was 93.0%. 4. Clinical efficacies were "excellent" in 1 patient with bacteremia, "excellent" in 6 and "good" in one of 7 patients with pneumonia, and "good" in both of the 2 patients with purulent meningitis. Clinical efficacies against other diseases were "excellent" or "good", in 1 patient with pyothorax, 1 patient with purulent lymphadenitis, and 2 patients with facial cellulitis. In 1 patient with biliary tract infection, the results of treatment with CPR were "unknown" due to insufficient clinical data. 5. No adverse reactions were observed except in 1 patient who showed an increase in platelet count. PMID- 1880928 TI - [New antimicrobial agent series XXXVIII: Cefotiam hexetil]. PMID- 1880929 TI - [New antimicrobial agent series XXXIX: Roxithromycin]. PMID- 1880930 TI - [Clinical studies on ciprofloxacin in chronic respiratory tract infection]. AB - Ciprofloxacin (CPFX), a new pyridone carboxylic acid, was administered orally to the patients with chronic respiratory tract infection and its clinical efficacy and safety were studied in a multicenter open trial. The results and summarized as follows. 1. The efficacy rate for the patients with acute exacerbation as 52.5% (21/40) in 2 week-treatment, and 75.0% (24/32) in 4 week-treatment. 2. The efficacy rate for the patients with chronic phase was 23.1% (6/26) in 2 week treatment, and 26.9% (7/26) in 4 week-treatment, but acute exacerbation was not observed in any of the patients. 3. CPFX was administered to 6 patients over 60 days for the prophylaxis of acute exacerbation. Only 2 patients had acute exacerbation in 2 and 3 months after the start of the therapy, respectively. 4. Bacteriological eradication rate was high except P. aeruginosa, for which the eradication rate was about 20%. 5. Side effects were observed in 3 patients, and abnormal findings of laboratory tests were observed in 5 patients, though they were not severe. These results show that CPFX is a useful antimicrobial agent for the treatment of chronic respiratory tract infections. PMID- 1880931 TI - [Laboratory and clinical studies on imipenem/cilastatin sodium plus amikacin sulfate in patients with severe infections complicating hematological disorders]. AB - Imipenem/cilastatin sodium (IPM/CS) and amikacin sulfate (AMK) were administered to 111 patients with severe infections complicating hematological disorders. Of the 111 patients, 93 were included in the present analysis of efficacy and 108 in that of safety. Twenty patients were evaluated as excellent, 37 as good, 8 as fair, and 28 as poor, with an overall rate of effectiveness of 61.3% (57/93). The synergistic interaction of IPM and AMK against clinical isolates (6 strains) was assessed in vitro using the checker board technique. Synergistic and additive effects were observed in 66.7% and 33.3% of the samples, respectively. Side effects were observed in 9 patients and abnormal laboratory test results in 2. These disappeared or returned to normal values after completion of therapy or discontinuation of IPM/CS and AMK. From the above findings, IPM/CS with AMK is considered to be a useful antibiotic combination for the treatment of severe infections complicating hematological disorders. PMID- 1880932 TI - [Combined antibacterial activity of aztreonam and clindamycin against clinically isolated strains]. AB - It has been reported in some studies that the combination of aztreonam (AZT) and clindamycin (CLDM) have high clinical effectiveness in the treatment of intractable infections. We, therefore, studied combined in vitro antibacterial activity of these 2 compounds using many freshly isolated strains. 1. AZT and CLDM in combination had synergistic effects on Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Haemophilus influenzae, which are sensitive or quasi-sensitive to CLDM, in the presence of CLDM at MIC or sub-MIC. 2. For Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, and Pseudomonas aeruginosa, which are not sensitive to CLDM, the 2 drugs in combination showed synergistic effects on some species and additive or slightly additive effects on most species in the presence of CLDM at those concentrations which are usually maintained in blood. 3. The 2 drugs showed no antagonism. PMID- 1880933 TI - [Clinical study on cefteram pivoxil in asymptomatic bacteriospermia]. AB - In order to understand the clinical efficacy of cefteram pivoxil (CFTM) in the treatment of asymptomatic bacteriospermia, the following studies were performed. 1. Concentrations of CFTM in the semen after oral administration of 200 mg to normal healthy adults (n = 5) reached a maximum level of 0.66 +/- 0.04 microgram/ml in 5 hours after the administration, then decreased rapidly, and averaged 0.15 +/- 0.03 micrograms at 7 hours after administration. 2. Activities of CFTM, cefaclor (CCL) and lomefloxacin (LFLX) against bacteria which were detected in semen (n = 65) (11 aerobic bacterial strains and 48 anaerobic bacterial strains) were retrospectively studied. The study of activities of these 3 agents against anaerobic bacteria showed that CFTM tended to be more active than CCL, LFLX, and similar tendency was noted in LFLX more than CCL against Peptostreptococcus sp. When penetration of antibiotic agents into semen is considered, however, some anaerobic bacteria as well as some aerobic bacteria may not be eradicated or inhibited, hence farther studies are needed to facilitate the selection of proper methods of administration as well as that of effective antibiotics. PMID- 1880934 TI - [Laboratory and clinical studies on cefpirome in pediatrics]. AB - Laboratory and clinical studies on cefpirome (CPR, HR 810), a newly developed cephem antibiotic, were performed. The results obtained are summarized as follows: 1. Absorption and elimination of the drug were examined in a total of 7 children including 3 cases of administered with 20 mg/kg intravenous bolus injection (i.v.), 2 cases with 20 mg/kg drip infusion (d.i.v.) for 60 minutes and 2 cases with 40 mg/kg (d.i.v.) for 60 minutes. Maximum serum levels were attained immediately after i.v. or d.i.v. Cmax's were 233 +/- 7.6, 88.5 +/- 14.5, and 116 +/- 15 micrograms/ml, respectively for the above 3 modes of administration. These values were determined using a bioassay method with Bacillus subtilis ATCC 6633. T 1/2 (beta)'s were 1.18 +/- 0.17, 1.61 +/- 0.28 and 2.68 +/- 0.83 hours, respectively. Cumulative urinary recovery rates were 40.2-69.8% in a period of 0 6 hours after admissions. 2. Clinical efficacies were evaluated in a total of 20 patients with ages ranging from 9 months to 11 years. The treated cases were 6 cases of acute pneumonia, 4 cases of acute bronchitis, 4 cases of acute purulent tonsillitis, 2 cases of acute urinary tract infections, 2 cases of cellulitis, 1 case of purulent lympadenitis and 1 case of acute otitis media. The clinical efficacy rate was 94.7%. Adverse reactions occurred in no patients. Abnormal changes in laboratory test values involved only 1 case with elevated GOT and GPT. CPR was considered to be a safe and useful drug in treating various infectious diseases in children. PMID- 1880935 TI - [In vivo and in vitro antifungal activity of fluconazole]. AB - We examined in vivo efficacy and in vitro activity of fluconazole, a novel triazole antifungal agent, and obtained results which are summarized as follows: 1. Fluconazole showed a higher serum concentration than ketoconazole after oral administration to mice. The 50% effective dose of fluconazole administered orally to mice was similar to that of fluconazole injected to mice intraperitoneally in a systemic candidiasis model. 2. Prophylactic effects of fluconazole were excellent against systemic candidiasis, cryptococcosis and aspergillosis in mice in comparison with those of ketoconazole and miconazole. 3. The multiple administration of fluconazole effectively decreased the number of viable cells of Candida albicans colonized in kidneys of mice when the serum level of fluconazole was kept to exceed its IC99 values against the inoculated pathogen. Thus, a good correlation between the in vitro activity of fluconazole and its in vivo efficacy was confirmed. In vivo efficacies of ketoconazole and miconazole, however, failed to reflect their marked in vitro activities. 4. C. albicans No. 32 developed no drug-resistance to fluconazole during transfers in medium containing fluonazole at a concentration of 1 micrograms/ml. PMID- 1880936 TI - [Metabolic disorders of lipoproteins--influences of compositional changes of lipoproteins upon their metabolic behavior]. AB - Compositional changes of apoproteins and lipids in lipoproteins influence their affinities for receptors and enzymes. Decrease of apo C proteins and increase of apo E in chylomicron and very low density lipoproteins (VLDL) during their catabolism might promote the binding to remnant receptor. On the other hand, the affinity for lipoprotein lipase (LPL) gradually decreases and that for hepatic lipase increases. However, the responsiveness of VLDL to LPL might be under the control of triglyceride (TG)/surface component ratios but not of the apoprotein ratios in ordinary circumstances judging from the results of the releases of fatty acids from VLDL by LPL in vitro. Responses of VLDL from diabetic patients to LPL significantly decreased compared with those from non-diabetic subjects. Glycation of VLDL in vitro impaired their responses to LPL. Therefore, delayed catabolism of VLDL in diabetes might partially depend upon glycation of VLDL besides the decreased LPL activity. Low density lipoproteins (LDL), apoproteins of which consist mostly of apo B protein and had a low TG level, showed a high affinity to the LDL receptor. However, LDL from hypertriglyceridemic subjects, in which the TG contents was increased, had a low affinity to the receptor. Since high density lipoproteins (HDL) from patients in acute phases contain a large amount of serum amyloid A protein (SAA), the percentages of apo A proteins markedly decreased. When SAA-rich HDL were incubated with leucocytes, SAA were degraded rapidly, although other apoproteins remained to be unchanged. Therefore, such HDL become unstable, and this might induce low HDL levels in the acute phase. PMID- 1880937 TI - [Laboratory evaluation of the Sysmex NE-7000 flagging system; a tool for the recognition of abnormal cells in white cell differentials]. AB - Sysmex NE-7000 flagging system was evaluated for the recognition of abnormal cells in white cell differentials. Six flags that could mark blasts, immature granulocytes, left shift, nucleated red blood cells, atypical lymphocytes, and platelet clumps were selected for evaluation. 182 morphologic abnormal samples were screened from the Kobe University Hospital patients, by means of the 600 eye counts differentials. Blasts flag missed 8 of 28 cases, and immature granulocytes flag missed 25 of 56 cases. These missed cases contained either relatively few abnormal cells; less than 3% immature granulocytes, or absolutely few cells; less than 201 per micro liter blasts. Platelet clumps flag missed only 2 of 23 cases. But nucleated red blood cells and atypical lymphocytes flags missed all of 7 and 4 cases respectively. Left shift flag missed 36 of 64 cases, but it could help marking immature granulocytes or blasts. To use the NE-7000 as a screening tool, we compared the NE's all 35 flags versus abnormal cells or status based on the 100 eye counts. 1,153 cases were analyzed. Full agreement; 1047 (90.8%), partial agreement; 61 (5.2%), distributional false normal; 7 (1.6%), and morphological false normal; 4 (4.6%), were obtained. The more flags were used, the less abnormal cases were missed. But it accompanied the increase of the flag positive cases that must be confirmed by eye. PMID- 1880938 TI - [Simultaneous detection of antibodies for 3 different retroviruses using retrovirus EIA (triple antigen kit)]. AB - We evaluated Retrovirus EIA kit (Roche Co.), in which virus components of three different viruses, HIV-1, HIV-2, and HTLV-I were used antigens. All the specimens from the patients with ATL, HAM, HTLV-I carrier, AIDS and AC, and from HIV-2 infected individuals were found to be positive. Four out of 40 specimens from hemophiliacs not infected with HIV-1 were found out to be positive. These specimens were confirmed to contain antibody against HTLV-I. Pseudo-negative or positive reactions were not found in this study. Therefore, Retrovirus EIA kit should be evaluated more extensively, for the possible applications for screening of blood donors, and for selecting the sources of blood products as well as for clinical diagnoses. PMID- 1880939 TI - [A study of the determination of serum fucose concentrations]. AB - We examined the biochemical properties of reaction products during the procedure for serum fucose determination (Dische & Shettles). The optical density at 396 nm (OD396) of the reaction products increased linearly with the increment of fucose concentrations, and was stable for at least 210-240 min at room temperature. The reaction products were destroyed with the addition of distilled water. Sephadex G 200 gel chromatography of the mixed serum samples revealed a single peak of fucose in the void volume fractions. Of interest was the presence of trace amounts of fucose detected in the low-molecular weight fractions less than 66,000, suggesting the presence of free fucose in the serum. Based on these observations, the method for serum fucose determination was modified so it was possible to use 100 microliters of the serum sample. The mean serum fucose concentration, measured by this modified method, was 561.0 +/- 191.1 mumol/l (9.1 +/- 3.1 mg/dl) in normal healthy children. In patients with idiopathic nephrotic syndrome, the values were significantly higher both at relapse and in remission than those in normal healthy children. PMID- 1880940 TI - [Effects of long-term low dose radiation--relationship between chromosomal translocation and the cellular oncogenes]. AB - To clarify the late effects of long-term exposure to low doses of radiation, chromosomal aberrations in the lymphocytes of radiological technologists (RT) were analyzed by the trypsin G-banding method. Structural aberrations were identified in 384 (2.5%) of 15,442 cells analyzed from 53 RT as compared to 177 (1.6%) of 11,136 cells from 36 healthy controls. Most of structural aberrations in both groups was translocations, and this frequency was significantly higher in the RT than in the controls. Translocations of chromosomes, such as Nos. 1, 2, 7 and 14 in RT and Nos. 1, 3, 7 and 14 in controls, was observed in over 7% of the cells. 7/14 translocations were the most frequent reciprocal translocations in RT. However, the frequency of 7/14 translocations was not significantly different between the RT and controls. In these cases, most of the break points were localized in band 14q11-12 and 7q32-36. At the chromosomal sites which were related to the sites of ski, abl, myb, mos, myc, N-myc oncogenes, very low incidences of translocation were detected in RT. However, none of the RT demonstrated abnormal clones of cells with identical chromosomal aberrations. PMID- 1880941 TI - [The development and the applications of clinical laboratory system by using of fuzzy set theory]. AB - For clinical laboratory data to be used effectively in wide areas of clinical medicine, it must be stored in proper database systems. Moreover, the system must be installed in the hospital information system for easy access by the hospital staff in their routine activities. From this standpoint we have developed a clinical test relational database system at Hiroshima University Hospital, which provides the functions of easy on-line retrieval and statistical analysis. We have also improved the functions to incorporate fuzzy query processing based on the theory of fuzzy sets. This system enables us to use natural linguistic representation and leads to a medical knowledge-base. PMID- 1880942 TI - [FDP levels in the cerebrospinal fluid are elevated in patients with meningitis]. AB - Since the level of fibrinogen degradation products (FDP) are elevated with severity of inflammation, we assumed that FDP in the cerebrospinal fluid (CSF) could be a marker of meningitis. We, therefore, measured FDP in the CSF of 6 patients with bacterial meningitis and 6 aseptic meningitis. The range of FDP levels in the CSF in patients without meningitis was 0.21 +/- 0.01 microgram/ml. While, the level of FDP in patients with aseptic meningitis (0.43 +/- 0.10 microgram/ml) and in bacterial meningitis (1.78 +/- 0.42 micrograms/ml) was significantly elevated (p less than 0.05). The value was significantly (p less than 0.01) higher in the group of septic meningitis than in aseptic meningitis. In one patient with septic meningitis, we could measure FDP in the CSF several times during the course of the disease, in which the level of FDP got into the high range earlier than the changes in levels of protein, glucose and cell counts in the CSF. FDP in the CSF well correlated to the clinical course of the meningitis. Eventually, we found that FDP in the CSF was definitely elevated in patients with bacterial meningitis, whereas it was slightly elevated in patients with aseptic meningitis. The measurement of FDP in the CSF, therefore, is concluded to be useful for the differential diagnosis of meningitis, and to assess the clinical course of meningitis. PMID- 1880943 TI - [Histological differences between sternal and iliac bone marrow in various hematological diseases]. AB - Even in normal state, hematopoietic activity is different in terms of the site of bone marrow as well as age. The activity may also differ with bone marrow site in various hematological diseases. We chose 32 cases with various hematological diseases and examined their bone marrow histologically at two different sites (sternum and posterior iliac crest) at almost the same time. We studied the histological differences in 5 cases of malignant lymphoma, 15 cases of aplastic anemia, 8 cases of myelodysplastic syndrome, 2 cases of myeloproliferative syndrome and 2 cases of acute leukemia. In malignant lymphoma, the iliac marrow was slightly hypoplastic compared with sternal marrow but there were no differences in the components of hematopoietic cells, that were thought to reflect normal hematopoietic activity for their respective ages. In 5 among 15 cases of aplastic anemia, nodular hyperplastic areas were observed in sternal marrow even though iliac marrow was severely hypoplastic. The presence of a nodular hyperplastic area is useful for differential diagnosis between aplastic anemia and refractory anemia, because such a histological change was not observed in the cases of refractory anemia. In myeloproliferative syndrome and acute leukemia, there were no differences between sternal and iliac marrow. They were hyperplastic and had almost the same hematopoietic components. PMID- 1880944 TI - [Studies on 13 cases of double gammopathy]. AB - By a combined use of immunoelectrophoresis and immunofixation, we detected 13 cases of double gammopathy among 269 cases of monoclonal gammopathy investigated between 1986 and 1990. The incidence of double gammopathy (4.8%) was greater than that in previous studies. Double gammopathy was classified into 5 groups: (1) identical pairs of both heavy (H)- and light (L)-chains (1 case); (2) identical H chains and different L-chains (2 cases); (3) different H-chains and identical L chains (3 cases); (4) different pairs of both H- and L-chains (5 cases); and (5) monoclonal immunoglobulin and Bence Jones protein of different type (2 cases). An additional M-component was detected during the course of illness in 2 of the 13 cases. As to H-chain combinations, a pair of IgG and IgA (46%) was most frequently encountered. Seven patients had myeloma, three benign double gammopathy and two macroglobulinemia. One case of benign double gammopathy developed IgA (lambda) myeloma three years after the diagnosis. Serum and urine immunofixation is a useful method to detect a trace amount of M-component and to follow up the clinical course of monoclonal gammopathy. PMID- 1880945 TI - [An autopsy case of primary lung leiomyosarcoma]. AB - We report autopsy findings for a case of leiomyosarcoma originating in the right lung in an 86-year-old man. We surveyed current literatures and compared the immunohistochemical results in the present case with those reported previously in Japan. The solid tumor measured 6 x 7 x 7 cm sized and was located in the right lung. Its cut-surface appeared grayish to yellowish and contained areas of hemorrhage and necrosis. The lungs contained scattered nodular lesions less than 2 cm in diameter. Metastatic lesions were also confirmed in other tissues such as the heart, pericardium, liver, spleen, left adrenal gland and thyroid. Microscopically, 14 mitoses were detected in every 10 high-power fields. An immunohistochemical study revealed positivity for smooth muscle myosin and actin, and negativity for CEA, and appeared to be important in differential diagnosis and determination of histogenetic type. PMID- 1880946 TI - [A case of paroxysmal cold hemoglobinuria (PCH) in the elderly found by severe anemia]. AB - CASE: 69 year-old female. Two weeks before the admission, the patient had suffered from upper respiratory tract infection. Severe anemia was detected (Hb was 6.0 mg/dl) and she received a transfusion. Four days after the transfusion, she became icteric and was transferred to our hospital on Feb. 3, 1990 for evaluation of anemia. Laboratory data on admission are as follows; Hb 6.3 g/dl, reticulocytes 128%, total bilirubin 4.6 mg/dl, indirect bilirubin 3.4 mg/dl, urobilinogen in urine positive, WR negative, direct anti-globulin test positive, indirect of the test negative, and Donath-Landsteiner test positive (both direct and indirect). Her red blood cells were classified as P2-positive. From these findings, non-syphilitic PCH was diagnosed. She required bed rest and therapy to protect her from cold exposure. The hemoglobin recovered to 8.3 g/dl. The D-L test was positive for 9 months. This is a rare case of PCH because the patient fell ill in old age and PCH was found because of her severe anemia in spite of her unawareness of hemoglobinuria. PMID- 1880947 TI - [Epidemiological study on the risk of gastric cancer in patients with duodenal ulcer]. AB - Patients who were diagnosed to have duodenal ulcer (DU) or duodenal ulcer scar (DUS) by gastric mass screening with X-Ray examination from April 1970 to Dec. 1983 were followed up to Dec. 1983 by means of record linkage to the Osaka Cancer Registry, and incident patients of gastric cancer (GC) among the study subjects during the follow-up period were investigated almost completely. Standardized incidence rates (SIR) of GC for the groups categorized by diagnosis at the initial screening, i.e., DU or DUS group and normal group, were calculated by comparing the number of GC among the study groups with the expected number of GC. This expected number was obtained by multiplying the person-year of the study subjects with GC incidence rates for the whole population of Osaka prefecture according to sex and age group. SIR were calculated by sub-groups, i.e., male and female groups, under 5 year follow-up (from the initial screening to GC diagnosis) and 5 year follow-up or over groups, and direct X-Ray examination at the detection center and indirect X-Ray examination in the screening bus groups. The results were as follows. The SIR were 0.41 for the DU or DUS group and 0.74 for the normal group. The risk for the DU or DUS group was lower than that for the normal group (R.R. = 0.55, chi 2 = 3.56, 0.1 greater than p greater than 0.05). In all subgroups, the risk of GC for each DU or DUS group was lower than that for the normal group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880948 TI - [Inhibition of gastric acid secretion normalizes interdigestive motor activity in the stomach in dogs]. AB - Recently, intragastroduodenal acidity has been shown to play an important role in interdigestive gastrointestinal motility. In this study, gastrointestinal motility and intragastric pH changes were monitored simultaneously in dogs, to characterize 1) the relationship between intragastric pH changes and IMC, and 2) the effects of intragastric acidity on motilin-induced phase III contractions in the gastric antrum by using secretagogues and an H2 receptor antagonist (cimetidine). As a result, intragastric pH showed periodic changes with gastric IMC in conscious dogs. Furthermore, motilin-induced gastric phase III contractions were inhibited by gastric acidification. But inhibition of gastric acid secretion by cimetidine normalized both the motor index and migration of the contractions. In conclusion, gastric acid secretion may influence the sensitivity to motilin of the stomach, and play an important role in the regulation of interdigestive gastric motility. PMID- 1880949 TI - [Immunohistochemical study on the expression of epidermal growth factor receptor (EGFR) in human colorectal carcinomas]. AB - The expression of epidermal growth factor receptor (EGFR) was studied immunohistochemically in 92 colorectal carcinomas: 21 early and 71 advanced. EGFR immunoreactivity was detected in 15 cases (16.3%) of colorectal carcinomas. All EGFR-positive cases was advanced carcinomas, while no EGFR immunoreactivity was found in early carcinomas. EGFR-positive cases were macroscopically 3.4 type and more than 2 cm in diameter. No significant correlation of EGFR expression with tumor location, stage, lymph node metastasis, degree of differentiation, and prognosis was found. All EGFR-positive cases was synchronous positive for the expression of EGF. These results suggest that EGFR may play an important role in tumor progression in cooperation with EGF. PMID- 1880950 TI - [Distribution of glutathione S-transferase isozymes in rat small intestinal mucosa]. AB - We have investigated the longitudinal distribution of glutathione S-transferase (GST) isozymes in the trisected small intestine mucosa of rats. Only GST subunits 1 and 7 were detected by Western blot analysis of the intestinal cytosol using antiserum for GST1-1, 1-2, 3-4 and 7-7. Cytosolic GST1-1, 3-4 and 7-7 were assayed by the quantitative ELISA. There was a marked decline of the concentration of GST1-1 from proximal (35.17 nmol/g tissue) to distal intestine (1.67 nmol/g tissue). GST3-4 was hardly detected in the intestinal mucosa. Among the GSTs, GST7-7 existed in the highest concentration in any segment of intestine, i.e. 58.76 nmol/g tissue (61% of GSTs) in the proximal intestine and 32.38 nmol/g tissue (93% of GSTs) in the distal intestine. PMID- 1880951 TI - [HLA-DR antigen expression on colonic epithelium of ulcerative colitis in comparison with infectious colitis and ischemic colitis]. AB - We examined HLA-DR antigen expression on endoscopically biopsied colonic epithelium of ulcerative colitis (UC), infectious colitis and ischemic colitis. Since this monoclonal antibody (LN-3 ICN Immunobiological, USA) is available for usual formalin fixated materials, if the fixation is limited within 36 hours. 886 samples from 55 UC cases, 91 samples from 19 infectious colitis cases, 63 samples from 15 ischemic colitis cases and 63 samples from normal cases were enough statistically, compared to DR antigen expression. UC expressed clearly statistical high positive DR staining rate than infections colitis and ischemic colitis. Further, samples from UC and infectious colitis were compared in the histopathologically each with the same grade of inflammation, UC expressed higher positive rates of DR antigen than infectious colitis, and both UC and infectious colitis showed increased positive rates of DR antigen with advance of histopathological grades of inflammation. PMID- 1880952 TI - [Experimental study on cell damage of ischemic liver in obstructive jaundiced rats]. AB - The hepatic cellular damage induced by liver ischemia was investigated in rats with obstructive jaundice. Hepatic tissue blood flow in obstructive jaundice was decreased in the relation to the duration of jaundice. The value of lipid peroxide and cathepsin D activity of the hepatic tissue increased in the obstructive jaundice. Therefore, it was suggested that cell membrane and lysosomal membrane injury were induced in obstructive jaundice. The value of lipid peroxide of hepatic tissue in obstructive jaundice was more increased after partial liver ischemia. The survival rate following hepatic ischemia in jaundiced rats was remarkably lower than that of normal rats, and also it related to the duration of jaundice. In addition, histological changes of the liver after partial ischemia are severe in obstructive jaundiced liver. These data suggest that more remarkable hepatic cellular damage than in normal liver may be induced by liver ischemia in obstructive jaundice. PMID- 1880953 TI - [Changes of Cu, Zn-SOD and LPO in the regenerating liver after partial hepatectomy--effect of coenzyme Q10 administration]. AB - We have investigated the effect of CoQ10 to lipid peroxide (LPO) and Cu, Zn-SOD in the regenerating liver in rats. Cu, Zn-SOD was investigated in biochemical activity, and immunohistochemical localization. In normal control liver, Cu, Zn SOD was diffusely stained throughout the hepatic lobules, with predominance in the centrilobular area and with vicinity of thick portal vein. In early stage of regenerating liver. LPO was increased and Cu, Zu-SOD was decreased. Destruction of the membrane of hepatocyte was confirmed by electron microscopy in the early stage of regenerating liver, Cu, Zn-SOD might be speculated to leak out into extra cellular spaces. CoQ10 suppressed the mentioned phenomenon in regenerating liver. PMID- 1880954 TI - [Hepatic resection under the Pringle maneuver induces endotoxemia and lipoperoxidative attack in the jaundiced rat liver]. AB - Sixty percent hepatectomy under two times of the Pringle maneuver (temporal occlusion of the hepatic inflow of the hepatic artery and portal vein) for 25 min was carried out on rats with obstructive jaundice. Hepatic energy charge which was markedly decreased during the Pringle maneuver did not recover 3 hrs after release of the maneuver. In addition, systemic endotoxemia associated with increased level of malondialdehyde and decreased levels of total glutathione and alpha-tocopherol in the liver was demonstrated. These changes were more dominant in rats with obstructive jaundice for 3 weeks than those for 1 week. It can be said that deteriorated hepatic energy charge after release of the Pringle maneuver may partly be caused by the production of oxygen free radicals which may be enhanced by endotoxemia in resection of the jaundiced liver. In contrast, after release of the Pringle maneuver, deterioration of hepatic energy charge due to oxidative attack was not found in jaundiced rats without hepatic resection. PMID- 1880955 TI - [Hemorrhagic esophageal ulceration associated with slow-release morphine sulfate tablets]. PMID- 1880956 TI - [A case report of primary microadenocarcinoma of the middle thoracic esophagus]. PMID- 1880957 TI - [A case of inflammatory fibroid polyp of the ileum--Review of inflammatory fibroid polyp of small intestine in Japan]. PMID- 1880958 TI - [Ulcerative colitis associated with pyoderma gangrenosum and schizophrenia--a case report]. PMID- 1880959 TI - [Primary hepatic leiomyosarcoma: the investigation of domestic and foreign 34 cases]. PMID- 1880960 TI - [A case report of mucin producing carcinoma with precancerous acinar cell lesions of the pancreas]. PMID- 1880961 TI - [Spontaneous rupture of the spleen in a case of infectious mononucleosis]. PMID- 1880962 TI - [Development of posture measuring apparatus using goniometer and inclinometer. 1. Description of the apparatus and its usefulness]. AB - A new posture measuring apparatus was developed for time and motion study in the field of industrial health. This apparatus can record and classify working postures by measuring the angles of joints and trunk inclination. The angles of joints are measured by newly developed goniometers which use the bending loss of rubber optical fibers. The trunk inclination is measured by an inclinometer which uses photointerrupters. The measured angle data stored in the memory of this apparatus are transferred to the host computer and analyzed. Postures are classified automatically and subjectively according to discriminant functions which are calculated from the preliminarily measured data by discriminant analysis. Test measurement was carried out to classify four postures; standing, forward bending, half sitting and sitting. The goniometers were set on the right hip joint, knee joint, and ankle joint and the inclinometer was set on the right side of the trunk. The postures were changed in the order of standing, forward bending, half sitting, and sitting every 30 s. The angles were measured every second and a total of 120 sets of angles were measured. All data including data during posture changing were classified correctly by discriminant functions. The measurement during baggage lifting up and putting down was also carried out. Ten baggages (each 7 kg in weight) were lifted up from the floor onto a desk (75 cm in height), put down back to the floor, and again lifted on the desk. In 2 min, baggages were lifted up for a total of 20 times and put down for a total of 10 times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880963 TI - [Effects of aging on contingent negative variation and reaction time]. AB - Contingent negative variations (CNV) were recorded at Cz for young, middle-aged and elderly groups of male and female subjects loaded with simple and discriminative sensory-motor tasks. Each task consisted of repeated single trials in which a warning signal (S1) of click tone was followed 4.0 s later by an imperative visual signal (S2) to which a quick motor response was required. The reaction time to S2 was also measured. In the simple task, a white circle of S2 was presented at probability of 75% on CRT screen, whereas in the discriminative task the subject was given either a green or red circle of S2 on CRT and asked to respond only to a green S2 with key-pressing. The negative component of the S1-S2 interval which was referenced as a baseline voltage during the 500 ms pre-S1 epoch was averaged over at least 12 single trials in each task. The reaction times were averaged over the trials in each task and used as a mean reaction time. A whole mean CNV amplitude averaged over the S1-S2 interval and 16 segmented CNV amplitudes of 250 ms epoch during the S1-S2 interval as well as the mean reaction time, number of erroneous responses and heart rates during both rest and task loading were obtained for each task. These parameters were submitted to 4-way ANOVA (age (3 levels) X gender (2) X task (2) X session (2)). The following age-related changes were observed: the whole mean CNV amplitude and the middle and late components of the segmented CNV decreased significantly with age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880964 TI - [An experimental study on transmission of hand-arm vibration on the body of users]. AB - Vibration forced into the hand-arm system was observed on the body surface during work with chain saw and under loading experiments by electrodynamic shaker in the laboratory, and factors related to transmission over joints were investigated using pig elbow joints constructed with ulna, radius and humerus. Vibration was measured according to IS 5349 and JIS C1511 between 8 and 1,000 Hz in vibration frequency. Vibration on the bone of pig foreleg conducted without attenuating its amplitude from the peripheral side to the central side between 8 and 1,000 Hz. On the other hand, vibration transmitted over joints damped its amplitude in higher frequency components rather than in lower frequency between 8 and 1,000 Hz. The decreasing ratio of transmitted vibration over joint was changed by the resonance of the soft tissues between the bones constructing the joint. The attenuation changed with the elastic modulus of the soft tissues. The peak frequency was considered to be the resonance because of the physical mass and elasticity. The harder the joint was tied, the stronger became the transmission, because the resonance moved to higher frequencies with increase in elastic modulus. In the loading test from the electrodynamic shaker to the hand-arm system of man, vibration on the soft tissues was transmitted on its surface as wave motion, when the vibration was observed over the skin on the soft tissues. Vibration reduced its amplitude at every joints especially above 100 Hz. The shape of the vibration attenuation curves varied according to the frequency and components of the chain saws.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1880965 TI - [Assessment of occupational exposure to p-tert-butylphenol in synthetic resin factories]. AB - Two cases of occupational vitiligo were observed in a resin factory where p-tert butylphenol (PTBP) has been used as a starting material or an intermediate of synthetic resin. In this resin factory (A shop) and another resin factory (B shop), occupational exposure to PTBP was assessed in workers charging this chemical into the reaction vessel by means of a gas-chromatographic measurement of the environmental PTBP concentration and their urinary PTBP excretion. Assessment in A shop was made after the working condition was partly improved. Geometrical mean values of 8 h-time-weighted-average (8 h-TWA) of PTBP in air near the charger's breathing zone (personal air) were 0.215 mg/m3 in A shop and 2.12 mg/m3 in B shop. Continuous measurements of PTBP concentration in some stationary air of the shops showed that the maximum environmental PTBP values occurred during charging. Urinary PTBP concentration was increased to the maximum values 2 to 4 h after charging of this chemical and then rapidly decreased. Biological half-lives of urinary PTBP were estimated as 4.4 h in A shop and 4.8 h in B shop. The urinary PTBP concentration was correlated to 8 h-TWA of PTBP in the personal air. In particular, PTBP in urine collected at the end of the shift showed an excellent correlation to PTBP in the personal air (r = 0.84, n = 9, A shop; r = 0.88, n = 11, B shop). These results indicate that biological monitoring using urinary PTBP concentration is a suitable means of assessing exposure to this alkylphenol and the urine collected at the end of shift is the best sample for monitoring. In addition, the present environmental and urinary PTBP values were compared with those described in the literature and the relation of the occupational vitiligo with PTBP exposure is discussed. PMID- 1880966 TI - [Acute effect of 1,1,1-trichloroethane inhalation on ventricular fibrillation threshold]. PMID- 1880967 TI - [Toxicity of isopropyl alcohol (IPA). Part 1. Single inhalation exposure in rats]. PMID- 1880968 TI - [Toxicity of isopropyl alcohol (IPA). Part 2. Repeated inhalation exposures in rats]. PMID- 1880969 TI - [Significance of diffuse slow washout in dipyridamole loading thallium-201 myocardial perfusion scintigraphy]. AB - To assess the significance of diffuse slow washout (DSW) in dipyridamole loading thallium-201 myocardial perfusion scintigraphy, 382 patients were studied. DSW were observed in 69 (24%) of 285 patients with perfusion defects, 5 (5%) of 97 patients without perfusion defects. There was significant relation between DSW and perfusion defects (p less than 0.01). Coronary angiography showed multivessel disease in 84% single vessel disease in 12% of patients with DSW and multivessel disease in 28%, single vessel disease in 50% of patients without DSW. During a mean follow up period of 29 months, initial CABG or PTCA were done in 41%, cardiac death occurred in 12%, nonfatal cardiac events occurred in 7% of patients with DSW and perfusion defects. In patients without DSW, initial CABG or PTCA were done in 11%, cardiac death occurred in 7%, nonfatal cardiac events occurred in 5%. Patients without perfusion defects had good prognosis regardless of the presence or absence of DSW. In conclusion, DSW indicates serious cardiac ischemia in patients with perfusion defects. DSW does not indicate cardiac ischemia in patients without perfusion defects. PMID- 1880970 TI - [Usefulness of thallium-201 myocardial SPECT using dipyridamole infusion combined with low level exercise for the detection of the ischemic heart disease- comparison with SPECT images by maximum physical exercise in the same patients]. AB - To evaluate the usefulness of thallium-201 myocardial SPECT using dipyridamole infusion combined with low level exercise (Dp-method) for the detection of the ischemic heart disease, we performed both Dp-method and maximum physical exercise SPECT (Ex-method) in the same 28 patients, and compared the results obtained by the two methods. In the visual evaluation, the detectability of each stenotic coronary territory by Dp-method tended to be higher than that by Ex-method (accuracy 71% vs 67%). The severity of the defect and the degree of the redistribution were higher by Dp-method than those by Ex-method. In the washout rate (WR) analysis in 14 angina pectoris patients, the detectability (accuracy) by Dp-method was significantly higher than that by Ex-method (86% vs 64%; p less than 0.05). In comparison of mean WR values in normal subjects (10 cases for Dp method and other 8 cases for Ex-method), mean WR by Dp-method was as high as that by Ex-method and the deviation of WR value among subjects was very small. This was probably due to the effect of the low level exercise. These results suggested that Dp-method was more excellent than Ex-method in the evaluation of the ischemic heart disease, and was a useful method of the daily routine work. The incidence of chest symptom and the electrocardiographic ST-depression was as high by Dp-method as that by Ex-method. The filling defects in Dp-method were thought to be induced not only by the difference in the relative increase of the myocardial perfusion, but also by the myocardial ischemia. PMID- 1880971 TI - [Basic evaluation of an ambulatory ventricular function monitor with a a cadmium telluride detector]. AB - The reliability of a new ambulatory ventricular function monitor (VEST) with cadmium telluride (Cd-Te) detector was validated. No counting loss was observed under 20 kcps. In phantom study, more than 200 ml with 6 cm distance from the detector and more than 300 ml with 6-12 cm distance, underestimation of volume was observed. Ejection fraction (EF) calculated in phantom study showed close value to the true EF in 50-400 ml of end-diastolic volume. In 10 patients, 1-2 cm detector shift toward right upper, upper and left showed underestimation of EF. Good correlation of gamma camera EF (X) and VEST EF (Y) was obtained (Y = 0.96X + 3.6(%), n = 37, r = 0.93, p less than 0.001). EF change from rest values, obtained from each comparable exercise and post exercise stage by gamma camera (X) and VEST (Y), showed good correlation (Y = 0.95X + 0.8, n = 20, r = 0.85, p less than 0.001). In conclusion Cd-Te VEST was considered as a reliable EF measurement technique similar to gamma camera. PMID- 1880972 TI - [Direct integral linear least square regression method for kinetic evaluation of hepatobiliary scintigraphy: theory, basic analysis and comparison with non-linear least square regression method]. AB - In hepatobiliary scintigraphy, kinetic model analysis, which provides kinetic parameters like hepatic extraction or excretion rate, have been done for quantitative evaluation of liver function. In this analysis, unknown model parameters are usually determined using nonlinear least square regression method (NLS method) where iterative calculation and initial estimate for unknown parameters are required. As a simple alternative to NLS method, direct integral linear least square regression method (DILS method), which can determine model parameters by a simple calculation without initial estimate, is proposed, and tested the applicability to analysis of hepatobiliary scintigraphy. In order to see whether DILS method could determine model parameters as good as NLS method, or to determine appropriate weight for DILS method, simulated theoretical data based on prefixed parameters were fitted to 1 compartment model using both DILS method with various weightings and NLS method. The obtained parameter values were then compared with prefixed values which were used for data generation. The effect of various weights on the error of parameter estimate was examined, and inverse of time was found to be the best weight to make the error minimum. When used this weight, DILS method could give close parameter values to those obtained by NLS method and both parameter values were very close to prefixed values. With appropriate weighting, the DILS method could provide reliable parameter estimate which is relatively insensitive to the data noise. In conclusion, the DILS method could be used as a simple alternative to NLS method, providing reliable parameter estimate. PMID- 1880973 TI - [Direct integral linear least square regression method for kinetic evaluation of hepatobiliary scintigraphy: clinical application and evaluation of 170 hepatograms]. AB - Kinetic evaluation of 170 hepatobiliary scintigrams was performed using direct integral linear least square regression method (DILS method). Liver time-activity curve (TAC) data were fitted to 2 types of 1 compartment model using heart TAC as input function. One model was 1 compartment model with 2 parameters (extraction rate (ku) and excretion rate (ke)), the other had another parameter for representing non-specific volume of distribution (Vn) in liver. Obtained parameter estimate was then examined to see how they correlate with three major visual findings of scintigram; low tracer uptake, intrahepatic cholestasis, extrahepatic cholestasis. In both models, ku showed significant difference between low uptake positive and negative groups and ke showed significant difference between extrahepatic cholestasis positive and negative groups. Only mean uptake time (Vn/ku) by 3 parameter model showed significant difference between intrahepatic cholestasis positive and negative groups, although the other 2 parameters (ku, ke) were insensitive to intrahepatic cholestasis in either model. Thus, the 3 parameter model was superior to the 2 parameter model because of its sensitivity to intrahepatic cholestasis and ability to differentiate extrahepatic and intrahepatic cholestasis as the difference of parameter values. Based on this 3 parameter model, parametric images were generated by calculating parameter value of each pixel using the DILS method. The DILS method could determine parameters by simple calculation, and hence was very powerful in processing parametric images, which processing otherwise required immense calculation. PMID- 1880974 TI - [Usefulness of 123I-IMP SPECT in patients with epilepsy]. AB - N-isopropyl-p-[123I]iodoamphetamine(123I-IMP)SPECT and electroencephalography (EEG) were evaluated in 21 epileptic patients at interictal stage. The findings of 123I-IMP were compared with those of clinical symptoms and EEG. In 11 cases (85%) of 13 patients with the partial seizure, and 6 cases (75%) of 8 patients with the generalized seizure had focal decreased perfusion of 123I-IMP. The mean number of focal decreased perfusion areas were 3.2 locations 1 case. There were no cases that was observed focal increased perfusion. Focal decreased perfusion area of 123I-IMP SPECT findings agreed with the focuses those were inferred from clinical findings in 8 cases (62%) out of 13 patients with the partial seizure, did not agree in 3 cases (23%) and did not detected in 2 cases (15%). Overall abnormality of 123I-IMP SPECT was observed in 17 cases (81%) out of 21 patients, on the other hand abnormality of EEG was observed in 12 cases (57%). 123I-IMP SPECT may provide useful information for evaluating foci in patients with epilepsy. PMID- 1880975 TI - [Experimental study on the accumulation of 125I-IMP in the cigarette-exposed lung]. AB - In the experiment using guinea pigs, the accumulated portions of IMP after 125I IMP microautoradiography were compared in a normal control group and a group exposed to cigarette smoke. In the smoke-exposed lung, the accumulation of silver grains were observed in the alveolar spaces and alveolar macrophages, as well as in the pulmonary capillaries and the alveolar epithelia. After the broncho alveolar lavage (BAL), increases in alveolar macrophages, total counts of BAL fluid and counts of cell components were seen in the smoke-exposed lung. These results suggested that abnormal function of the pulmonary capillary or alveolar epithelium was wide spread in the smoke-exposed lung. PMID- 1880976 TI - [An adult case of the left coronary artery anomalously originating from the pulmonary artery (BWG syndrome), demonstrating remarkable improvement in postoperative thallium-201 myocardial imaging]. AB - Stress thallium-201 myocardial scintigraphy were performed in a 44-year-old female with BWG syndrome before and after aorto-coronary bypass surgery. Preoperative stress thallium-201 studies demonstrated anterior reversible perfusion defect and posterior persistent defect. But postoperative studies demonstrated no defects in both areas. These data suggest that preoperative anterior defect was due to transient myocardial ischemia, but the finding of posterior persistent defect wasn't due to infarction or scarring. Thus, stress thallium-201 myocardial imaging provided useful informations to clarify the myocardial perfusion patterns pre- and postoperatively. PMID- 1880977 TI - [Dose estimation of Tc-99m-DTPA-galactosyl-human serum albumin (Tc-99m-GSA) in the blood with nonlinear regression method]. AB - Tc-99m-DTPA-galactosyl-human serum albumin (Tc-99m-GSA) was applied as an agent for receptor-binding hepatic scintigraphy. A single dose of 3-10 mg/185 MBq (5 mCi) Tc-99m-GSA per body was administered in four healthy volunteers and three patients. Time-activity curves for 60 (40) min after injection were obtained from the regions-of-interest over the heart and lung (back-ground). Exponential regression curve was generated from the heart curve during 2-60 (40) min after background subtraction with nonlinear least squares method. Regression curve was well fitted to the heart curve and a significant correlation coefficient of 0.997 +/- 0.003 was obtained between these two curves. Absolute dose of GSA in the blood was decided on the assumption that extrapolated value of regression curve at time 0 represented the total injected dose. The absolute dose differences between sample blood and regression curve were 1.4-4.3% (mean). Nonlinear regression analysis is useful for estimating quantitative dose of GSA in blood without any blood samples. PMID- 1880978 TI - [Analysis of I-125-IMP and its metabolites using a high performance liquid chromatography]. PMID- 1880979 TI - Chronopharmacology of the new uricosuric diuretic S-8666 in rats. AB - A new loop diuretic with uricosuric activity, 6,7-dichloro-5-(N,N dimethylsulfamoyl)-2,3-dihydro-2-benzofuran carboxylic acid (S-8666), was given orally at 12:00 a.m. or 12:00 p.m. in rats. The diuretic of S-8666 and the urinary excretions of the drug and its active metabolite S-8680 (N-demethyl S 8666) were greater at 12:00 a.m. than at 12:00 p.m. Thus, the present study indicates that the diuretic effects of S-8666 varies with its administration time. Time-dependent variations in the amount of urinary excretions of S-8666 and S-8680 might be involved in the mechanisms for this phenomenon. PMID- 1880980 TI - The external Ca(2+)-dependence of acetylcholine-induced contracture in single innervated and denervated skeletal muscle cells in mice. AB - We examined morphological differences and compared the Ca(2+)-dependence between acetylcholine (ACh)-contractures in normal and denervated skeletal muscle cells. ACh (1 microM - 1 mM) contracted the normal cells into a jackknife-shape. The higher the concentration of external Ca2+, the greater the ratio of responding cells/total cells observed and the sharper the angles of the "jackknives". ACh contracted the denervated cells into a compression-form, and the contraction was dependent on the external Ca2+. These results indicate that ACh-contractures in both normal and denervated cells are external Ca(2+)-dependent. PMID- 1880981 TI - Basic fibroblast growth factor and epidermal growth factor promote survival of primary cultured cerebellar neurons from neonatal rats. AB - Neurotrophic effects of CS23, a mutein of human basic fibroblast growth factor (bFGF), and recombinant human epidermal growth factor (hEGF) were compared in dissociated cerebellar cultures from embryonic (E20) and early postnatal (P0-5) rats. Both CS23 and hEGF promoted the survival of cerebellar neurons without distinction of ages of animals used. The maximum effects of CS23 were always larger than those of hEGF. These results suggest that both bFGF and EGF also function as neurotrophic factors in postnatal cerebellum. PMID- 1880982 TI - Functional reinnervation of carotid artery by implanted preganglionic trunk in the cat. AB - The preganglionic trunk of the superior cervical ganglion was implanted chronically into the carotid artery. A helical strip of the carotid artery with nerve was prepared, and electrical stimulation of the nerve caused a definite contraction. Part of the contraction was attenuated by phentolamine, and the remaining part of the contraction was nearly abolished by tubocurarine but not by hexamethonium and atropine. The present results clearly demonstrate that the carotid artery is reinnervated by preganglionic cholinergic fibers. PMID- 1880983 TI - A difference in receptor mechanisms for muscarinic full and partial agonists. AB - Concentration-response curves of 4 muscarinic full agonists were progressively inhibited by 10 to 50-min treatments of the longitudinal muscle of guinea pig ileum with propylbenzilylcholine mustard (PrBCM, 3 x 10(-6) M). A 90-min treatment with PrBCM had no further significant inhibitory effect on their curves. The 50-min treatment with PrBCM (3 x 10(-6) M) completely inhibited the concentration-response curves of 6 partial agonists. The limiting effect of PrBCM observed on the concentration-response curves of the full agonists was not found on the curves of the partial agonists. These results suggest that there are two subtypes of M3-cholinoceptors, PrBCM-sensitive receptors and PrBCM-resistant ones. Pilocarpine, a partial agonist, shifted the concentration-response curve of carbachol, a full agonist, in a parallel fashion in the strips treated with PrBCM (3 x 10(-6) M) for 50 min, suggesting that an interaction of pilocarpine with PrBCM-resistant cholinoceptors does not induce contraction. The full agonists contract the longitudinal muscle through the interaction of two cholinoceptors, PrBCM-sensitive and -resistant ones, while the partial agonists produce the contraction through the activation of PrBCM-sensitive ones. PMID- 1880984 TI - Effects of brain biogenic amines of repeated treatments with calcium antagonists. AB - Discrete brain sections were obtained from rats once or repeatedly (once a day for 5 days) given i.p. nifedipine, verapamil or diltiazem at doses ranging from 5 to 20 mg/kg. The biogenic amines and metabolites in the hypothalamus, brainstem, hippocampus, striatum, cortex and thalamus-midbrain were determined by high performance liquid chromatography with electrochemical detection. The drug induced changes, displaying regional specificity and differences according to the various compounds, suggested that: (a) serotonergic systems were activated, especially in fasted rats or after repeated treatment; (b) the dopaminergic system of the striatum was inhibited by nifedipine which did reduce the HVA levels and the HVA/DA, as well as the DOPAC/DA, ratio. These effects disappeared after repeated treatment. It was also speculated that the data obtained could be of great interest in view of the possible use of calcium antagonists to treat disorders of the central nervous system. PMID- 1880985 TI - Chronopharmacology of the new uricosuric diuretic S-8666 in rats: (II). Examination in aged rats. AB - We have previously demonstrated a time-dependent variability in the diuretic effects of S-8666, a new loop diuretic with uricosuric activity, in young rats. The present study was undertaken to determine whether such a daily variation in the effects of the agent exists in aged rats. S-8666 (30 and 90 mg/kg) was orally given at 12:00 a.m. (day trial) or at 12:00 p.m. (night trial) in young (10-11 week old) and aged (23-24 month old) Wistar rats. Urine was collected for 8 hours after the agent; and urinary excretions of sodium, S-8666 and its active metabolite S-8680 were determined. Urinary excretions of volume and sodium following S-8666 at 12:00 a.m. were greater than those at 12:00 p.m. in the young and aged animals. Urinary excretions of S-8666 and S-8680 were also greater in the day trial compared to those in the night trial in both groups of rats. In the day and night trials, there were significant correlations between urinary S-8666 + S-8680 and the diuretic effects in both groups of rats. These findings indicate that the diuretic effects of S-8666 also vary with its time of dosing in aged rats. The time-dependent variations in urinary S-8666 and S-8680 might be involved in this phenomenon. PMID- 1880986 TI - Decrease in muscle tension and reduced pyridine nucleotides of the guinea pig ileal longitudinal smooth muscle in high K+,Na(+)-deficient solution. AB - In the present experiment, we studied the inhibitory mechanism of Na+ depletion on high K(+)-induced contraction by simultaneously measuring reduced pyridine nucleotides (PNred) or oxidized flavoproteins (FPox) fluorescence and contractile tension of the guinea pig ileal longitudinal muscle. Tension, PNred and FPox were all reversibly increased by the addition of hyperosmotic 65 mM KCl (H-65K+). A high K+, Na(+)-deficient (Iso-154K+) solution induced a contraction followed by a gradual relaxation and gradually decreased PNred fluorescence. A hyperosmotic addition of NaCl to the Iso-154K+ solution prevented the decreases in tension and PNred fluorescence. Addition of pyruvate or oxaloacetate restored the decrease in Iso-154K(+)-induced contraction, but not the decrease in PNred fluorescence. In contrast to the PNred fluorescence, an application of the Iso-154K+ solution increased the FPox fluorescence which was not significantly changed by an addition of NaCl, pyruvate or oxaloacetate. These results suggest that the inhibitory mechanism of Na+ depletion on the Iso-154K(+)-induced contraction is an inhibition of glucose utilization. PMID- 1880987 TI - Effects of antiestrogens on ovarian aldo-keto reductase in relation to ovulation in rats. AB - The pharmacological effects of antiestrogens on ovarian aldo-keto reductase and ovulation were investigated in rats. The activities of reduction of 13,14-dihydro 15-keto-PGF2 alpha, 4-benzoylpyridine and menadione in ovarian cytosol were significantly decreased by antiestrogen treatments, and the ovulation was completely inhibited. However, administration of luteinizing hormone-releasing hormone at 3:00 p.m. on the day of proestrus restored both enzyme activities and ovulation, which were inhibited by antiestrogens, to control levels. These results indicate that nonsteroidal antiestrogen inhibits the luteinizing hormone surge on the day of proestrus in 4-day cycling rats and that ovarian aldo-keto reductase may be closely involved in the ovulatory process in rats. PMID- 1880988 TI - Observation of the development of tolerance to and physical dependence on barbital by cortical evoked potential in rats. AB - To observe the dispositional and functional tolerance to and physical dependence on barbital, the influence of repeated administration of the drug on serum barbital levels, coordinative motion, body weight, and cortical evoked potential was assessed. Rats administered the first dose of barbital showed marked impairment of gross behavior and then loss of the righting reflex. While they were repeatedly treated with barbital for a 4-week period, the CNS depression became weaker and weaker, and loss of the righting reflex was no longer observed. Serum barbital levels after administration of barbital tended to decrease by the 28th day of repeated drug administration. Coordinative motion was markedly impaired after administration of the first dose, but gradually recovered during the repeated administration period. Barbital at 100 mg/kg, i.p., prolonged the latent time of the evoked potential in normal untreated rats but not in tolerant rats. During the withdrawal period, no particular change was observed in the animals' gross behavior. However, body weight loss and shortening of the latent time of the evoked potential were observed at 60 to 72 hours of withdrawal. These results suggest that cortical evoked potential can serve as a useful method for observing tolerance to and physical dependence on barbital. PMID- 1880989 TI - Effects of NZ-107 on tracheal responses to adenosine in the guinea pig. AB - We have investigated the effect of NZ-107, an inhibitor of bronchoconstriction induced by slow reacting substance of anaphylaxis (SRS-A), on tracheal responses to adenosine in the guinea pig. In the presence of an adenosine uptake inhibitor, dipyridamole (1 microM), NZ-107 (0.3-1 microM) enhanced adenosine-induced relaxation in 30 nM leukotriene D4 (LTD4)-precontracted trachea, whereas aminophylline (AP, 10-30 microM), an adenosine receptor antagonist, markedly inhibited it. NZ-107 (1 microM) also enhanced the relaxation induced by forskolin, an adenylate cyclase activator, but not that by nitroprusside (NP), a guanylate cyclase activator. AP (30 microM) affected neither forskolin- nor NP induced relaxation. NZ-107 (1 microM) and AP (30 microM) inhibited to about the same extent the contractile response to an adenosine A1 receptor agonist, the R( )-enantiomer of N6-(2-phenylisopropyl)-adenosine (R-PIA). The R-PIA-induced contraction was completely blocked by 5 microM indomethacin. NZ-107 (1 microM) did not affect the contraction induced by PGD2, but significantly reduced that of PGF2 alpha. AP (30 microM) had no effect on PGF2 alpha- and PGD2-induced contractions. These results suggest that NZ-107 may have a unique profile for adenosine responses in bronchial asthma. PMID- 1880990 TI - Changes in convulsion susceptibility of lidocaine by alteration of brain catecholaminergic functions. AB - Influences of the manipulation of brain catecholaminergic neuronal activity on the incidence of lidocaine-induced convulsions in mice were studied and compared with those of pentylenetetrazol (PTZ)-induced convulsions. alpha-Methyl-p tyrosine (alpha-MPT) decreased both brain noradrenaline (NA) and dopamine (DA) levels, and disulfiram decreased the NA level and increased the DA level. The incidence of lidocaine-induced convulsions was decreased by treatments with alpha MPT and disulfiram, while that of PTZ was increased by either treatment. The incidence of lidocaine-induced convulsions was slightly, but not significantly increased by L-dihydroxyphenylalanine (L-DOPA), although the brain DA level was increased by L-DOPA. Methamphetamine and desipramine increased the incidences of lidocaine-induced convulsions. These results may suggest that brain catecholaminergic neurons, differing from their role in inhibiting control of PTZ seizure, act to facilitate lidocaine-induced convulsions. PMID- 1880991 TI - The response to acoustic stimulation and the changes in brain amine levels after repeated administration of beta-phenylethylamine in rats. AB - Reverse tolerance to stereotyped behavior was induced after repeated administration of beta-phenylethylamine (PEA) (50 mg/kg, i.p., daily for 10 days) in rats. The reverse tolerance was maintained for at least 4 weeks after the last administration. We studied the effects of acoustic stimulation on locomotor activity 2 days and 4 weeks after withdrawal from PEA and measured the changes in brain monoamine levels 4 weeks after the withdrawal. Locomotor activity during acoustic stimulation was increased in the saline treated group, and this response was unaffected after repeated PEA treatment. Four weeks after withdrawal, significant increases in noradrenaline levels in the cerebral cortex and decreases in 5-hydroxytryptamine levels in the hypothalamus were found. The effects of acoustic stimulation on locomotor activity and the changes in brain monoamine levels were different from those of methamphetamine treatment obtained in our previous study. In conclusion, it may be suggested that the response to acoustic stimulation after repeated PEA administration in rats cannot be a model for abnormal responsiveness to environmental stimulation that is observed in chronic paranoid schizophrenics. PMID- 1880992 TI - Histological detection of lipid peroxidation following infusion of tert-butyl hydroperoxide and ADP-iron complex in perfused rat livers. AB - Lipid peroxidation was assessed histologically and biochemically in hemoglobin free perfused rat livers using two different types of stimulators. The Schiff reaction of fuchsin with cellular aldehydes was used as a histological index for lipid peroxidation. t-Butyl hydroperoxide (BHP, 0.8 mM) infusion caused a rapid and sustained release of thiobarbituric acid reactive substances (TBARS) into the effluent perfusate for up to 60 min, which was accompanied by lactate dehydrogenase (LDH) leakage after 30 min. The Schiff positive foci were initially restricted to periportal zones and spread with time to whole areas, accompanied by periportal necrosis. Coinfusion of diphenyl-p-phenylenediamine suppressed the TBARS release, with negative fuchsin staining, but the LDH leakage was unaffected. Under retrograde perfusion, BHP produced pericentral staining and necrosis. With 2.5 mM ADP-100 microM Fe3+, little TBARS was released up to 60 min, even though the hepatic TBARS levels increased considerably by this time. By 90 min, marked TBARS release occurred, but LDH leakage remained low. Irrespective of the direction of perfusion, pericentral hepatocytes became Schiff positive after 30 min. The fuchsin staining method may be useful for detecting peroxidized zones of the liver lobules. PMID- 1880993 TI - Histological evidence for dissociation of lipid peroxidation and cell necrosis in bromotrichloromethane hepatotoxicity in the perfused rat liver. AB - Bromotrichloromethane (CBrCl3)-induced hepatic lipid peroxidation and cell necrosis were studied histologically and biochemically, using isolated perfused livers from phenobarbital-pretreated rats. Lipid peroxidation was assessed by fuchsin staining of the liver slices and release of thiobarbituric acid reactive substances (TBARS) into the perfusate; necrosis was assessed by trypan blue uptake and lactate dehydrogenase (LDH) leakage. A good correlation was observed between the Schiff-positive reaction and TBARS release under various experimental conditions, supporting the validity of the fuchsin staining method for histological detection of lipid peroxidation. Lobular localization of lipid peroxidation and necrosis was as follows: Under high oxygen supply (95% O2 saturated buffer), infusion of CBrCl3 caused the Schiff-positive reaction in the pericentral to midzonal hepatocytes, irrespective of the direction of perfusion, but did not produce necrosis. Under low oxygen supply (20% O2) with retrograde perfusion, dissociation of lipid peroxidation and necrosis was observed, i.e., trypan blue uptake in the periportal zones and Schiff-positive staining in the pericentral hepatocytes. Thus, lipid peroxidation by itself may have a relatively minor role in the development of CBrCl3-induced acute hepatic cell death. PMID- 1880994 TI - Propylbenzilycholine mustard (PrBCM)-sensitive cholinoceptors and contractile response to partial agonist in guinea pig ileal muscle. AB - Pilocarpine, a partial agonist, activates propylbenzilylcholine mustard (PrBCM) sensitive cholinoceptors in the guinea pig ileal longitudinal muscle, while carbachol, a full agonist, predominantly activates PrBCM-resistant ones. Carbachol behaves as a partial agonist in the preparation treated with phenoxybenzamine and mainly activates PrBCM-sensitive cholinoceptors, as phenoxybenzamine preferably blocks PrBCM-resistant ones. The receptor occupancy response curve for carbachol became a rectangular hyperbola, while pilocarpine showed a linear relation. After occlusion of cholinoceptors with phenoxybenzamine, carbachol showed a linear receptor occupancy-response relation, suggesting that its contraction mechanisms after occlusion of cholinoceptors resemble those for pilocarpine. Both the agonists induced an increase in cytosolic Ca2+ concentration [( Ca2+]i) and tension development in a concentration-dependent manner under the conditions used herein. The slopes of the regression lines between [Ca2+]i and tension development for pilocarpine in the untreated preparation and for carbachol in the preparation treated with phenoxybenzamine were significantly steeper than that for carbachol in the untreated preparation, suggesting that carbachol in the phenoxybenzamine-treated preparation and pilocarpine induced a greater tension for a given increase in low [Ca2+]i than did carbachol. Thus an activation of PrBCM-sensitive cholinoceptors might enhance the Ca2+-sensitivity of the contractile elements. PMID- 1880995 TI - The inhibitory effect of a novel antiatheromatous agent, E5050, on the intimal thickening of aorta in cholesterol-fed rabbit in vivo. AB - The development of atheromatous lesions in the aortic arch of 0.5% cholesterol fed rabbits was biochemically and morphologically examined. The animals were killed at week twelve (Cont-12W) or sixteen (Cont-16W). Both the micrographic and biochemical studies showed that the main atheromatous lesions in the Cont-12W group were fatty streaks, whereas those in the Cont-16W group were fibrous plaques. In these models, oral ingestion of 0.2% and 0.4% E5050, which has an antiproliferative effect on smooth muscle cells, had no effect on the surface involvement or the lipid content of the aortic arch at the sixteenth week, but reduced the degree of intimal thickening and the DNA content in the aortic arch in a dose-dependent manner. These results strongly suggest that E5050 suppresses the intimal thickening through its inhibitory effect on the proliferation of smooth muscle cells. PMID- 1880996 TI - The effects of saikosaponin-d on yeast phagocytosis and degradation in peritoneal macrophages: related increase in Fc receptor expression and altered cytoplasmic organization. AB - The effects of saikosaponin-d (ssd), isolated from Bupleurum radix, on phagocytic functions of mouse peritoneal macrophages were investigated in macrophage cultures after treatment in vivo. We also compared the ultrastructural appearances of macrophages from ssd-treated mice with those from control mice. The macrophages from ssd-treated mice showed a significant increase in phagocytosis, intracellular killing of yeast and acid phosphatase activity. Treatment of mice with ssd also induced the Fc receptor expression in macrophages. The macrophages from ssd-treated mice showed more intense spreading on a glass surface than those from the control mice after a 60 min-incubation. Furthermore, the macrophages from ssd-treated mice seemed to possess a well developed Golgi apparatus and the large vacuoles. The data suggest that the functional changes in the macrophages from ssd-treated mice are brought about by a modification in the surface membrane and the intracellular distribution. PMID- 1880997 TI - Anti-nicotinic and anti-muscarinic actions of eperisone in the isolated canine atrium. AB - The effects of eperisone, an antispastic agent, on the chronotropic and inotropic responses to acetylcholine, nicotine or stimulation of intracardiac autonomic nerves were evaluated in isolated, blood-perfused canine atrium. Eperisone (10 300 micrograms) injected into the sinus node artery of the isolated atrium produced dose-related negative chronotropic and inotropic effects, which were not affected by atropine. In the same doses, eperisone inhibited the negative chronotropic and inotropic responses to an injection of acetylcholine and intracardiac parasympathetic stimulation. Eperisone also suppressed the negative followed by positive cardiac responses to nicotine, but did not modify the positive responses to intracardiac sympathetic stimulation or norepinephrine. The inhibitory effect persisted much longer for the responses to nicotine or parasympathetic stimulation than for those to acetylcholine. These results suggest that eperisone at doses that induce direct cardiac depressant effects exerts its blocking action on nicotinic receptors at parasympathetic ganglia and sympathetic nerve terminals and on muscarinic receptors at the effector cells in the dog heart. PMID- 1880998 TI - Inhibitory effect of a biscoclaurine alkaloid, cepharanthin, on lung metastasis of Lewis lung carcinoma. AB - The antimetastatic effect of cepharanthin with or without 5-fluorouracil (5-FU) was examined in an experimental model of lung metastasis induced by Lewis lung carcinoma (3LL) in C57BL/6crSlc mice. Injection of cepharanthin i.p. after removal of the implanted primary tumor inhibited the development of lung metastases. Combination therapy with cepharanthin plus 5-FU inhibited significantly the lung metastases. Lung metastases were inhibited by i.v. injection of peritoneal macrophages activated with cepharanthin. Cepharanthin depressed aniline hydroxylase and aminopyrine demethylase activities of the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover, the concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood) was increased significantly by coadministration of cepharanthin. A possible mechanism of the inhibition of lung metastases by treatment with cepharanthin may be that this drug acts through macrophage activation and depression of the hepatic microsomal drug-metabolizing system. These findings raise the possibility that combination therapy with cepharanthin plus 5-FU may have clinical value in the prevention of cancer metastasis. PMID- 1880999 TI - Inhibitory regulation of serum factor(s)-caused ornithine decarboxylase induction by the protein kinase C system in A431 human epidermoid carcinoma cells. AB - Replacement of the culture medium with fresh medium containing 10% fetal calf serum caused ornithine decarboxylase (ODC) induction in A431 human epidermoid carcinoma cells. Two peaks of ODC activity were observed at 5 and 14 hr after the medium replacement. The peak activity observed at 5 hr was more prominent than that at 14 hr. The first peak of ODC induction was suppressed by a potent protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), in a concentration-dependent manner. The second peak, however, was not suppressed by TPA. Other potent protein kinase C activators, such as mezerein and 12-O retinoylphorbol-13-acetate, also suppressed the first peak of ODC induction. Synthetic diacylglycerols, 1,2-dioctanoyl-sn-glycerol and 1-oleoyl-2 acetylglycerol, did not inhibit the serum factor(s)-caused ODC induction. Phorbol 13-acetate, an inactive phorbol ester, also failed to inhibit the ODC induction. The growth of A431 cells was slightly suppressed by TPA. In protein kinase C down regulated cells, TPA failed to inhibit the serum factor(s)-caused ODC induction. These results suggest that the serum factor(s)-caused ODC induction in A431 cells is negatively regulated by the protein kinase C system, which may not be activated by exogenous diacylglycerols. PMID- 1881000 TI - Withdrawal like responses of rat hippocampal slices following brief exposure to morphine. AB - An acutely acquired dependence was investigated in rat hippocampal slices after brief exposure to morphine. Morphine augmented the population spike amplitude. Naloxone not only reversed the augmentation but decreased the amplitude to a level below that of the control. The inhibitory effect of naloxone correlated with the period of preincubation with morphine. These results suggested that the decreased response may indicate the withdrawal state acquired in vitro. PMID- 1881001 TI - Exacerbation of doxorubicin toxicity by chlorpromazine in male ddY mice. AB - We examined whether chlorpromazine (CPZ) modulates the lethality of doxorubicin (DOX, 12 mg/kg, i.p.) in mice treated with CPZ (6 mg/kg, i.p.) 1 hr before administration of DOX. Pretreatment with CPZ produced: 1) earlier deaths and 2) an increase in the number of deaths, compared to the controls. Potentiation of the bone marrow toxicity of DOX by CPZ was also reflected in the drug lethality towards the animals. PMID- 1881002 TI - Prolonged inhibition of vascular contraction and calcium influx by the novel 1,4 dihydropyridine calcium antagonist cinaldipine (FRC-8653). AB - We examined the effects of FRC-8653, a novel dihydropyridine calcium antagonist, on the contraction of an arterial preparation and the calcium influx into vascular smooth muscle cells to clarify the long-lasting hypotensive activity of this drug. Inhibition by FRC-8653 persisted for more than 7 hr after its removal, whereas nifedipine and nicardipine exhibited shorter durations of suppressive activity. These results suggest that prolonged inhibition of calcium influx through L-channels contributes to the long-lasting vasodilative and antihypertensive activity of FRC-8653. PMID- 1881003 TI - Effects of bifemelane hydrochloride, a brain function improver, on muscarinic receptors in the CNS of senescence-accelerated mouse. AB - Senescence-accelerated mouse (SAM-P/8) is known as a murine model of aging and memory dysfunction, compared with control mouse (SAM-R/1). In the hippocampus of 9-month-old SAM-P/8, the Bmax of [3H]QNB binding was decreased compared with that of SAM-R/1 at the same age. Single and repeated administrations of bifemelane to SAM-P/8 induced an increase in the Bmax of [3H]QNB binding in the hippocampus. From these results, bifemelane seems to exert pharmacological effects through possible activation of the cholinergic system in the hippocampus of SAM. PMID- 1881004 TI - Diurnal variation in the diuretic effects of nitrendipine in saline loaded rats. AB - We have previously reported that the responsiveness of blood pressure to nitrendipine, a dihydropyridine calcium antagonist, varies with its time of administration. The present study was undertaken to examine whether the diuretic effects of the agent also show diurnal variation. Nitrendipine was given orally at 12 a.m. or 12 p.m. to rats, and urine was collected for 8 hours after administration. The urine volume and urinary sodium excretion were greater at 12 p.m. than at 12 a.m. These data indicate that the cardiovascular as well as renal effects of nitrendipine vary with its time of administration. PMID- 1881005 TI - Intracellular Ca2+ and Mg2+ regulation for insulin-stimulated glucose uptake into mouse diaphragm muscles. AB - We investigated whether the changed levels of intracellular Ca2+ and Mg2+ in mouse skeletal muscles affected insulin-stimulated glucose uptake. Insulin alone had no effect on 45Ca2+ efflux and uptake. A23187 at 20 microM increased 45Ca2+ influx and inhibited insulin-stimulated 14C-glucose uptake with normal external concentrations of Ca2+ and Mg2+ or in the absence of both cations. These results suggest that the increase in Ca2+ influx into, and in Mg2+ efflux from, skeletal muscles may inhibit insulin-stimulated glucose uptake. PMID- 1881006 TI - Difference in pressor responses to NG-monomethyl-L-arginine between conscious and anesthetized rats. AB - NG-Monomethyl-L-arginine (L-NMMA; 0.1-10 mg/kg, i.v.), a selective inhibitor of nitric oxide (NO) synthesis derived from L-arginine, elicited a greater increase in blood pressure in urethane/alpha-chloralose- and pentobarbital-anesthetized rats than in conscious Wistar rats. The pressor response to phenylephrine was almost equivalent in both conscious and anesthetized rats. These findings suggest that the experimental conditions (anesthetized or conscious) modify the spontaneously released NO's contribution to blood pressure regulation in vivo. PMID- 1881007 TI - [Clinical study on occupational uroepithelial cancer]. AB - We experienced 32 cases of occupational uroepithelial cancer at Jichi Medical School Hospital from 1974 to 1990. All of them were dyestuff workers who had been engaged in production or handling of benzidine, beta-naphthylamine or alpha naphthylamine. In these 32 cases, upper urinary tract tumors were found in 7 cases, one of these having bilateral lesions. The mean age when the tumor of the urinary tract was first disclosed was 48 years old, with a range of 36 to 66 years old. The mean age of this occupational group was about 16 years younger than that of the spontaneous urinary tract tumor group in our hospital. We divided our cases into two groups according to duration of carcinogen exposure; less than 5 years and 5 years or more. However we did not obtain significant difference in the grade of tumors or prognosis between the two groups. But when we divided them into two groups according to the type of work; production group and handling group, 18 of 21 production workers had high grade tumors. On the other hand, only 3 of 11 handling workers had high grade tumors, which was a significant difference. Besides, 10 of 21 production workers or only one of 11 handling workers were fatal. The difference was also significant. There was no significant correlation among the type of work, the duration of exposure and the age of onset. In our study, we showed that the type of work was quite important to predict the grade of tumors and the prognosis in occupational uroepithelial cancer patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881008 TI - [A study of the metabolism of vitamin D in patients with renal cell carcinoma- with special reference to serum concentration of 1 alpha, 25-(OH)2D and its clinical significance]. AB - Recently it has been known that the active form of vitamin D, 1 alpha, 25 dihydroxyvitamin D (1 alpha, 25-(OH)2D), plays some immunological roles in controlling cell differentiation and carcinogenesis. Moreover, 1 alpha, 25-(OH)2D is said to have some effects in the changes of several numbers of oncogenes. In this study, the serum concentrations of 1 alpha, 25(OH)2D and 25-hydroxyvitamin D (25-(OH)2D) were measured in 30 patients with renal cell carcinoma. The two vitamin D metabolites were separated and purified using high performance liquid chromatography, and each fraction was subjected to competitive protein binding assay using vitamin D deficient rat serum for 25-(OH)2D and chick embryo intestinal receptors for 1 alpha, 25-(OH)2D as the binder. The average concentration of serum 1 alpha, 25-(OH)2D was 28.9 +/- 5.2 pg/ml for controls whereas the average in patients with renal cell carcinoma was 19.7 +/- 5.9 pg/ml. The concentration of 1 alpha, 25-(OH)2D was significantly lower in the patients with renal cell carcinoma compared to in the controls (p less than 0.01). The average concentrations of serum 25-(OH)2D had no significant differences between the two groups. Comparison between the stage I + II and stage III + IV, T1 + T2 and T3 + T4, rapid type and slow type groups showed that the average serum 1 alpha, 25-(OH)2D concentrations was significantly lower in the stage III + IV, T3 + T4, and rapid type groups compared to the other groups (p less than 0.01, p less than 0.05, p less than 0.01). And besides there were no significant correlations between the concentration of serum 1 alpha, 25-(OH)2D and creatinine clearance in patients with renal cell carcinoma. Taken together, it is suggested that the serum concentration of 1 alpha, 25-(OH)2D is in some way correlated with the progression of renal cell carcinoma. PMID- 1881009 TI - [The significance of bacillus Calmette-Guerin in the therapy of carcinoma in situ of the bladder]. AB - We treated ten patients with carcinoma in situ of the bladder (primary type, 6 and secondary type, 4) by intravesical bacillus Calmette-Guerin therapy. All patients received 8 weekly instillation, and among them 3 patients were followed by additional instillation monthly for 7 months. Complete regression (negative biopsies and cytology study) was observed after 8 weekly instillation in all patients. To elucidate the mechanism of action of BCG on carcinoma in situ, the biopsied specimens after BCG instillation were examined light and electronmicroscopically. It was speculated that BCG might act on cancer cells in two ways: one was sloughing and denudation of the cancer cells by acute tuberculous cystitis, and the other was a role of the macrophages through immune reaction. In our study, the toxicity and complications seemed to be much severer than previously reported. Vesicoureteral reflux was observed in 6 patients. Decreased bladder capacity noted in all patients, among them radical cystectomy and colocystoplasty were performed in 2 patients under the diagnosis of bladder contracture. Although complete regression was observed in all patients after 8 weekly BCG instillation, the duration being free from cancer cells was variable. And we also discussed on the additional therapy in such patients in the literature. PMID- 1881010 TI - [Studies on the multiple-drug induction immunosuppressive therapies with cyclosporine after renal transplantation]. AB - Our induction immunosuppressive therapies were carried out on patients split into three groups. The first group of 25 recipients were treated with regimen I [cyclosporin (CsA); 12 mg/kg/day and prednisolone (Pred)]. The second group of 16 recipients were treated with regimen II [CsA; 6 mg/kg/day, Pred and mizoribine (MIZ) or azathioprine (AZA)]. The third group of 14 recipients were treated with regimen III [CsA; 10 mg/kg/day, Pred and MIZ or AZA]. There was no significant difference among the three groups in renal function three months after renal transplantation. The frequency and grade of rejection were significantly higher in Group II than in the other groups. One of group I had CsA nephrotoxicity and none of group III had liver dysfunction three months after renal transplantation. Group I had a higher incidence of posttransplant hypertension. Hypertension of group I was very severe. We concluded that the triple-drug therapy on group III was the best induction immunosuppressive therapy after renal transplantation of the above three. PMID- 1881011 TI - [Percutaneous management of benign ureteroileal anastomotic strictures after ileal conduit urinary diversion]. AB - We report our experience with the endourological treatment of 4 patients with 5 benign ureteroileal anastomotic strictures after ileal conduit urinary diversion. The treatment was successful in 4 of the 5 renal units without restenosis with a mean follow up of 10 months. The strictures were dilated by ureteral dilators and/or balloon dilation catheters using guide wires through percutaneous nephrostomies in an antegrade fashion. A 9 or 12 Fr. percutaneous splint catheter or a 12 Fr. double pig tail catheter was placed for 3-8 weeks after a successful dilation. Two renal units underwent repeated dilations. In 1 renal unit, a guide wire was hardly passed through the stricture and the treatment was unsuccessful. No serious complications were encountered. Percutaneous endourological managements of ureteroileal anastomotic strictures seemed to be quite versatile techniques which should be tried as the initial approach in many cases. PMID- 1881012 TI - [Effects of olfactory tubercle stimulation on efferent activities in the vesical branch of the pelvic nerve and in the urethral branch of the pudendal nerve in dogs]. AB - Experiments were performed to elucidate the effects of stimulation of the olfactory tubercle on the urinary bladder and external urethral sphincter in 31 dogs anesthetized with ketamine and alpha-chloralose and immobilized with gallamine. The hypogastric nerve was severed in all dogs, and the bladder was filled with Tyrode's solution under constant pressure (15-20 cmH2O). The outflows of the pelvic vesical branch (PV) and the pudendal urethral branch (PU) and isotonic vesical contractions were recorded simultaneously. Stimulation (5-100 Hz, 3 msec, 0.2 mA) was applied through a unipolar platinum electrode (50 microns, in diameter) inserted into the olfactory tubercle from the ventral surface. Olfactory tubercle stimulation elicited PV excitation (bladder contraction) and concomitant PU inhibition (urethral relaxation), but no reverse effect. Electrical stimulation was applied to the excitatory points at varied frequencies (5-100 Hz). PV excitation and bladder contraction were produced at 10, 20, 50 and 100 Hz, but not at 5 Hz. In another group, the vesicopressor pathway from the tubercle was investigated by partial sectioning of the brain stem in dogs from which the left fore- and mid-brain had been previously removed. The vesicopressor response induced by tubercle stimulations was not abolished by sectioning of the medial preoptic area, medial hypothalamus or periaqueductal grey, but was abolished by sectioning of the lateral preoptic area, lateral hypothalamus or ventral mesencephalic tegmentum, respectively. At the rostral pontine level, the response was abolished by partial sectioning of the lateral part of the pontine reticular formation ipsilateral to the stimulation. PMID- 1881013 TI - [Study of satellite tumor nodules in renal cell carcinoma]. AB - Topography and histological types of main tumor and satellite tumor nodules (STN) were investigated on 60 cases of renal cell carcinoma by gross and microscopic study by making whole area histological sections. 30-100 histological slides were made from the median sagittal section and multiple horizontal sections of renal cell carcinoma. STN were observed in 28 cases of the 60 cases (46.7%) and could be classified into 3 types according to their location relative to the main tumor. STN could not be observed in some cases despite the large main tumor of 10 cm or more, while STN were observed in some cases with the main tumor of only 2.5 cm or less. High grade and high stage cases showed a high incidence of STN. It is considered that, only in cases, with the tumors of low grade, low stage and has only 1 STN or less, conservative surgery on renal parenchyma is possible. When the case is of low grade and low stage and has a possibility of preserving normal renal parenchyma, conservative surgery on renal parenchyma may be justified even if the tumor is large. PMID- 1881014 TI - [Clinical studies of bacteriuria in renal transplantation recipients. Correlation with pyuria and symptomatic genitourinary tract infection]. AB - The clinical state of bacteriuria and its correlation with pyuria and symptomatic genitourinary tract infection (GUTI) were studied in 42 renal transplantation recipients who were followed up in the Kidney Center of Tokyo Women's Medical College over 6 months and who showed bacteriuria more than 3 times between January and December in 1987. The results were as follows. 1) Of the 42 recipients, bacteriuria was found less than 5 times in 19 patients, 6 to 10 times in 18 patients and more than 11 times in 5 patients. There was a tendency for the same bacteria to be isolated several times from the same patient. The most commonly isolated bacterias were Enterobacter, Enterococcus, Serratia and E. coli. 2) Bacteriuria was accompanied by pyuria in 33 patients (79%) and by symptomatic GUTI in 12 patients (29%). Bacteriuria without pyuria was shown in 9 patients (21%) without symptomatic GUTI and it was suggested that bacteriuria did not result in graft hypofunction after two years. 3) Of 16 patients with bacteriuria accompanied by pyuria, symptomatic GUTI occurred in 9 patients (56%). Of these, one patient was found to have VUR of the transplanted kidney, another was found to have VUR of the native kidney, and a third patient died due to interstitial pneumonitis presumably as a result of overimmunosuppression. Transplantation recipients with bacteriuria accompanied by pyuria develop symptomatic GUTIs frequently and should be treated with proper antibacterial agents. When bacteriuria continues, further examination should be performed for an organic disease of the urinary tract or an overimmunosuppressed state. When a patient shows bacteriuria without pyuria, chemotherapy is not needed and it is sufficient to observe the course carefully. PMID- 1881015 TI - [Continuous monitoring of penile rigidity and tumescence in Japanese without erectile dysfunction]. AB - Continuous monitoring of penile rigidity and tumescence has been proved to be of use for accurate diagnosis of erectile impotence, since it provides objective recording of penile rigidity as well as circumferential expansion. Prior to clinical use of this procedure in Japan, a study was performed to clarify normal features of nocturnal penile tumescence of Japanese and to ensure safety of this procedure. The subjects consisted of 16 normal volunteers, aged from 24 to 44 years. With fully informed consent of the volunteers, nocturnal penile rigidity and circumferential expansion were simultaneously measured for three consecutive nights by means of RigiScan at the base of the penis (base) and at about five millimeters proximal to the coronary sulcus (tip). The minimum circumference of the penis was 62.7 +/- 4.6 mm (mean +/- SD) at the tip and 65.4 +/- 9.3 mm at the base. The maximum circumference, which meant full erection in the normal volunteers, was 102.5 +/- 14.2 mm at the tip and 108.6 +/- 14.7 mm at the base. The mean duration of tumescence, i.e. circumference expansion more than 10 mm, was 23.0 +/- 6.9 minutes at the tip and 38.3 +/- 12.0 minutes at the base. The mean rate of episodes of circumference expansion more than 10 mm was 0.75 +/- 0.27 per hour at the tip and 0.70 +/- 0.26 per hour at the base. The maximum rigidity lasting more than 10 minutes was 82.9 +/- 10.1% at the tip and 85.4 +/- 8.4% at the base.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881016 TI - [The meanings of the papaverine test]. AB - Intracavernous administration of papaverine is now commonly employed for diagnosis and therapy of impotence. To assess the pharmacokinetics of papaverine, we recorded its concentration in peripheral blood and also in cavernous blood after intravenous and intracavernous injection of 40 mg of papaverine. Peripheral blood was sampled serially after injection. Plasma was immediately extracted and then kept at at -40 degrees C until analysis. High pressure liquid chromatography was used to record the concentration of papaverine. The maximum serum concentration of papaverine measured after intracavernous injection was 7.7 ng/ml, which was considerably lower than the average serum concentration of 24.0 ng/ml after intravenous injection. Peak serum concentration was reached 1 min after intravenous injection and 10 min after intracavernous injection. It is clear that the corpus cavernosum constitutes a separate pharmacokinetic compartment. Therefore there was no significant difference between the papaverine concentration in peripheral blood of patients who showed full erection after intracavernous injection and that of patients who did not achieve erection. The concentration of papaverine in the intracavernous blood of a fully erected penis was only about 1 microgram/ml after 20 min. This concentration is similar to that in cavernous blood of those who showed excessively persistent erection. Our results imply that papaverine administered into the cavernous space relaxes smooth muscle, and is then washed out to general circulation, and the concentration in the cavernous space reaches a low level of about 1 microgram/ml. The low concentration level is maintained for several hours during erection. Therefore, we presume that papaverine acts on both the inflow system and smooth muscle of cavernous tissue in the phase of producing erections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881017 TI - [Histopathological findings of prostate carcinoma--nuclear anaplasia (NAN) and structural atypism (SAT)]. AB - Most of the previous publications have focused mainly on structural atypism (SAT) or differentiation in the studies on histopathological findings of prostate carcinoma. We studied nuclear anaplasia (NAN) as well as SAT in prostate carcinoma, comparing with differentiation grade or Gleason's pattern, to find NAN's clinical implication. We also compared histopathological findings of prostate carcinoma in our cases with those in U.S.A. Analysis of NAN grade and SAT grade distribution in stages revealed a correlation between the grades and the stages, in which SAT1 or NAN1 decreased while SAT3 or NAN3 increased in their frequencies as stage progressed. A similar correlation was found between mean value of SAT + NAN grade and stage. While NAN grade and SAT grade agreed with each other in 70% of the patients with prostate carcinoma, that was not the case in the remaining patients. This suggested a complementary relationship between NAN grade and SAT grade in some patients. A similar relationship was found between NAN grade and Gleason's pattern. These results suggest that, in a non negligible number of patients, the NAN grade does not agree with the SAT grade or Gleason's pattern which is defined by atypism in the glandular structure. Disease specific survival in each SAT grade could be further defined by the NAN grade. For example, in both SAT2 and SAT3, NAN3 tended to have a poorer prognosis than NAN2. Thus, NAN grading system would furnish more accurate information to predict the patients' clinical course.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881018 TI - [Clinical observations of plasma fibronectin in patients with urological malignant disease]. AB - Fibronectin (FN) is a high molecular weight glycoprotein widely distributed in the body and has a number of biological activities. Recently, there have been reports on the relationship between plasma fibronectin (pFN) levels and malignant diseases, but the significance of pFN is still unclear. Using immunoturbidimetric assay, we measured pFN levels of 24 healthy controls and 61 patients with urological malignant diseases, and obtained the following results. 1. pFN levels before treatment. 1) pFN level was 379 +/- 60.6 micrograms/ml and 356 +/- 123.7 micrograms/ml in the healthy controls and patients, respectively. There was no significant difference. 2) pFN level in patients with metastases was 320 +/- 92.9 micrograms/ml and had no statistical difference as compared with patients without metastases (371 +/- 132.7 micrograms/ml) and controls, despite the decrease in the mean value. 3) pFN level in patients with poor prognosis (300 +/- 107.8 micrograms/ml) was significantly lower than that in patients with good prognosis (410 +/- 157.2 micrograms/ml) and controls (p less than 0.05). 2. pFN levels during conservative treatments for advanced disease. pFN level in patients with a rapid progressive disease (287 +/- 64.4 micrograms/ml) was significantly lower than that in patients with a slow progressive disease (327 +/- 43.3 micrograms/ml) (p less than 0.01). These data suggest that low pFN level predicts rapid progression of the disease and poor prognosis in patients with a urological malignant disease. PMID- 1881019 TI - [Surgical enucleation for renal cell carcinoma. A case report]. AB - We present a case of bilateral synchronous renal cell carcinoma treated with surgical enucleation. Urological consultation was asked to evaluate masses of the kidneys, which were detected during a diagnostic imaging on a 58-year-old man with hepatic disorder. Excretory urograms showed definite bilateral upper pole renal masses. Bilateral selective renal angiograms disclosed neovascularity in the small masses. Surgical enucleation of the left renal tumor by a flank approach was performed. The surgical specimen being 3.5 by 2.5 by 2 cm (29 g) was pseudoencapsulated and was identified renal cell carcinoma of the clear cell type, grade 1. INF alpha, pathologically. Seven weeks after, a pseudoencapsulated tumor of 3 by 2.5 by 2 cm (16 g) in the right upper pole was removed by simple enucleation. The pathological diagnosis was renal cell carcinoma of clear cell type, grade 2, INF alpha. The patient is well without evidence of recurrent or any residual disease at 21 months after the second operation. Renal function remains with in normal limits (CCr 110 ml/min). Of our collected cases of bilateral synchronous renal carcinomas treated by bilateral conservative surgery, clinical data are available for 11. Including our case, a total of 12 cases are reviewed. PMID- 1881020 TI - Benign breast disease. PMID- 1881021 TI - Anticoagulants in heart disease. PMID- 1881022 TI - Home run. PMID- 1881023 TI - Third-party payers and the physician's duty of confidentiality. PMID- 1881024 TI - Recent developments in diagnosis and treatment of nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma (NPC) is one of the major cancers that Chinese radiotherapists have to treat, because of its high incidence which shows a tendency to increase. Although results of radiotherapy in NPC have improved markedly during the last decade, treatment at an early stage of the disease is the most effective. It is therefore important to make the diagnosis early, and recently serological surveys by IgA/VCA show its efficacy in high risk populations. Histological diagnosis so far has not correlated to prognosis, and new histological classifications have been proposed by many authors. The importance of CT scans in diagnosis and treatment is stressed. Criteria for clinical staging of NPC will have to be reconsidered, especially the T staging, as 80% of cases formerly classified as T1 may already have paranasopharyngeal extension, as shown on CT scans. The technique of radiotherapy has not changed much essentially since the advent of telecobaltherapy. However, various institutions have their own special variations. The most striking advance is the use of high-dose rate afterloading brachytherapy as boost for residual disease or as main treatment for nasopharyngeal recurrences. Finally, the role of chemotherapy in the radiation treatment of NPC is discussed, and the paper concludes with some remarks on the future outlook in the diagnosis and treatment of NPC. PMID- 1881025 TI - Treatment of Graves' orbitopathy in 1990. AB - In a mechanical sense, we understand how the orbital changes and the symptoms of endocrine ophthalmopathy develop. Expansion of the retrobulbar tissues results in forward displacement of the globe beyond the protective cover of the eyelids. Lymphocytic infiltration, followed by fibrosis of the extraocular muscles and the eyelid retractors, leads to diplopia and corneal exposure. Glycosaminoglycans, which are water binding molecules, accumulate in the retrobulbar tissues of patients with orbitopathy and add to the bulk to the retrobulbar tissues. Proptosis at first serves to relieve retrobulbar pressure but eventually the restrictive action of the extraocular muscles and the orbital septum limits protrusion of the globe. As forward motion is restricted, pressure from the expanded tissues rises in the confined retrobulbar space, and the optic nerve may be compressed and functionally impaired. If one thinks of the central problem in orbitopathy as being a discrepancy between the volume of the bony orbit and the bulk of the tissues it is supposed to contain, then it follows that effective treatment must either shrink the swollen tissues or make more space available for them. Medical therapy attempts to shrink the swollen tissues by steroids, radiotherapy or cyclosporin. Surgery relies on making more space available for the swollen tissues and can be modified for each patient. Further rehabilitation for diplopia can be managed with prisms or extraocular muscle surgery. Non-urgent eyelid surgery follows completion of extraocular muscle surgery. Close collaboration with an interested endocrinologist is essential. PMID- 1881026 TI - Anti-Ro(SSA) and anti-La(SSB) antibodies in lupus erythematosus and Sjogren's syndrome. AB - Anti-Ro(SSA) and La(SSB) antibody determinations have become important serologic tests in the evaluation of lupus erythematosus and Sjogren's syndrome patients. These antibodies appear to identify a group of lupus patients with prominent skin diseases. Although much of the initial investigations regarding the value of these antibodies has been performed in the United States and Europe, preliminary studies suggest that the frequency of these antibodies in Japanese and other Oriental patients may be double that seen in American patients. This article will briefly review our knowledge of the molecular, immunogenetic and clinical features of the anti-Ro(SSA) and anti-La(SSB) antibody responses. PMID- 1881027 TI - Antitumor efficacy of doxorubicin in combination with cisplatin on human lymphoma cells at various cell densities in vitro. AB - The influence of tumor cell density on the antitumor effect of doxorubicin (DXR) in combination with cisplatin (CDDP) was studied in vitro using DND-39A lymphoma cells. DXR was progressively less effective on colony formation inhibition when cell density was increased from 10(5) to 10(8) viable cells/ml (positive inoculum effect), whereas the effect of CDDP was not influenced by cell densities. At a density of 10(5) cells/ml, inhibition of colony formation was virtually identical irrespective of cells being exposed to DXR and CDDP either simultaneously or sequentially. When cell density was increased to 10(7) and 10(8) cells/ml, sequential exposure to CDDP followed by DXR was more active than simultaneous or reversed order of exposure to the two drugs. These results indicate that for DXR CDDP combination chemotherapy against the cells at high density, the proper sequence of the treatment should be the administration of CDDP followed by DXR, rather than simultaneous or reversed order of exposure. Inoculum effect may be an additional determinant for the rational development of combination chemotherapy. PMID- 1881028 TI - Biochemical analysis of glycosphingolipids in murine uterus and human uterine endometrium with special reference to the sexual cycle. AB - Uterus is an organ in which cellular proliferation and differentiation are strictly controlled by sex steroid hormones. Since we found a characteristic expression of sulfatide (I 3SO3-GalCer) in the human endometrium during its secretory phase, we decided to analyze developmental changes of glycolipids in murine uteri with special reference to the estrous cycle. Moreover, we analyzed sulfotransferase activity for the synthesis of sulfatide in the endometria in the proliferative and secretory phases and that in the epithelial and stromal cells derived from the human uterine endometrium. In the murine uterus, contents of GlcCer, LacCer, and Gb4Cer were relatively constant both during estrus and diestrus, but those of Gb3Cer and Gg4Cer during estrus were significantly greater than those during diestrus. In contrast, GM3 and sulfatide contents during diestrus were higher than those during estrus. This increase in GM3 and sulfatide during diestrus was characteristically observed in the uterus after sexual maturity. In human uterine endometrium, sulfotransferase activity for the synthesis of sulfatide was found only in the epithelial cells, but not in the stromal cells. Furthermore, the synthetic potential of sulfatide in the human endometrium was higher in the secretory phase than in the proliferative phase. Thus, sulfatide metabolism in human endometrial epithelial cells as well as in the murine uterus is supposed to be well controlled under hormonal regulation, and sulfatide may participate in several reproductive functions of the uterus. PMID- 1881029 TI - Clinical heterogeneity in acute myelogenous leukemia with the 8;21 translocation. AB - Nine acute myelogenous leukemia(AML) patients with a translocation 8;21, who were treated at Keio University Hospital between 1983 and August 1990, were reviewed. All of them were classified into AML-M2 subtype of the French-American-British classification. It formed 43% of all M2 cases. The patients' mean age was 47 years. Neutrophil alkaline phosphatase score was lower than normal and complete remission(CR) was achieved in all cases. In statistical analysis, patients with the t(8;21) showed a longer CR duration and a higher percentage of eosinophils than the other AML-M2 patients without this karyotype (p less than 0.05, p less than 0.01, respectively). As an additional chromosomal abberation, two patients showed a loss of Y chromosome at first diagnosis and another patient did a deletion of 12p at the 3rd relapse and an elongation of 20q in addition to the 12p- at the 4th relapse. Although patients with the t(8;21) are regarded as a favorable group in respect of survival, we found a subset of patients who had poor prognosis. Some of them were accompanied with solid tumor formation. Only one patient has lived longer than 5 years. These findings suggest that AML with the t(8;21) is clinically heterogenous. PMID- 1881030 TI - Tubuloglomerular feedback activity after acute reductions in renal mass. AB - Removal of one kidney results in prompt increases in urinary excretion of NaCl and water from the remaining kidney, followed rather soon thereafter by increases in glomerular filtration rate (GFR). At 12-15 h and 24 h after contralateral nephrectomy, the single nephron filtration rate (SNGFR) is increased, accompanied by parallel increases in absolute proximal tubular reabsorption, late proximal tubular and early distal tubular flow rates, suggesting that these events might be critical to the increased urinary excretion. However, micropuncture studies 2 4 h after contralateral nephrectomy demonstrate that increased SNGFR and even increased distal tubular flow rates are not requirements for augmented urinary excretion, suggesting that decreased tubular reabsorption in the most distal nephron segments causes the increase in urinary excretion. Analysis of TGF profiles by stop-flow pressure response at 2-4 h after contralateral nephrectomy have suggested suppression of TGF as assessed by a rightward shift in the turning point with increasing late proximal tubular perfusion. However, our studies have examined SNGFR responses and shown no suppression of TGF profiles but a downward shift in the operating point, suggesting activation of TGF and a modest reduction in SNGFR, determined from distal tubular collections. Although SNGFR was increased at all late proximal perfusion rates 12 h after nephrectomy, the turning point (V 1/2) was not altered. TGF profiles are not suppressed within 12 h after nephrectomy while SNGFR is increased. Suppression of TGF does not cause the increase in SNGFR after nephrectomy and TGF activity is maintained and adapts to increases in SNGFR caused by TGF-independent mechanisms. PMID- 1881031 TI - Tubuloglomerular feedback in renal hypertrophy. PMID- 1881032 TI - Tubuloglomerular feedback in obstructive uropathy. AB - The tubuloglomerular feedback (TGF) mechanism was studied in rats with chronic partial ureteral occlusion (hydronephrosis) with the use of the stop-flow pressure techniques and measurements of single nephron glomerular filtration rate. In hydropenic conditions, TGF was normal in hydronephrotic kidneys, but TGF sensitivity and activity increased in response to extracellular volume expansion, which is the opposite of normal resetting. The increased sensitivity may be due to an increased production of thromboxane A2 in the hydronephrotic kidney, since both inhibition of thromboxane synthetase and blockade of thromboxane/prostaglandin endoperoxide receptors normalized the resetting during volume expansion. Pelvic pressure in hydronephrotic kidneys was low in hydropenia and increased moderately during volume expansion. Thromboxane synthesis inhibition before volume expansion allowed pelvic pressure to increase by more than 100% as compared with untreated hydronephrotics. Also, when pelvic pressure increases were prevented during volume expansion, TGF resetting was normalized. An increased thromboxane synthesis during volume expansion may be protective in hydronephrotic kidneys, in that TGF resets to a higher sensitivity to prevent increases in glomerular filtration rate and urine formation which otherwise would increase pelvic pressure. A resetting to a higher sensitivity was also elicited by intraarterial or intratubular administration of bradykinin. This suggests that thromboxane release may be mediated through an increased bradykinin production during volume expansion in hydronephrotics. In contrast, bradykinin resets TGF to a lower sensitivity in control kidneys. PMID- 1881033 TI - Tubuloglomerular feedback in one-kidney, one-clip hypertensive rats. AB - Previous studies have shown that hydropenic one-kidney, one-clip (1-K, 1-C) hypertensive HT rats exhibit impaired autoregulation of glomerular filtration rate (GFR) in response to reduced arterial perfusion pressure. We investigated the possible role of altered tubuloglomerular feedback (TGF) activity in this phenomenon. Uninephrectomized Wistar rats were studied acutely 3 weeks after placing silver clips (0.2 mm) on the renal artery. Experiments were performed in 1-K,1-C HT rats and in uninephrectomized control animals. TGF activity was assessed as changes in proximal tubule stop-flow pressure (SFP) in response to orthograde microperfusion from 0 to 80 nl/min into late proximal tubule segments. Only the highest perfusion rates (approximately 40 nl/min) into late proximal tubule segments resulted in maximal decreases in SFP, indicating a marked rightward shift of overall TGF activity in 1-K,1-C HT rats. Similar responses were observed in the uninephrectomized animals. In contrast, changes of SFP were observed at lower perfusion rates in normal animals and maximal responses were observed at perfusion rates of approximately 20 nl/min. These observations are consistent with the possibility that altered TGF activity contributes to impaired autoregulation of GFR in 1-K,1-C HT rats in response to reduced renal perfusion pressure. In response to treatment with i.v. captopril, the 1-K,1-C HT rats exhibited marked decreases in systemic arterial pressure associated with decreases in SFP and virtually complete inhibition of TGF activity. It is attractive to hypothesize that these alterations in TGF characteristics in the 1 K,1-C HT rats play a significant pathophysiologic role in the acute renal dysfunction observed in response to acute decreases of blood pressure during conditions of augmented angiotensin activity. Additional future studies will allow us to address the precise role for intrarenal angiotensin in these phenomena. PMID- 1881034 TI - Tubuloglomerular feedback response in rats with antithymocyte serum-induced glomerular lesions. AB - Glomerular function and tubuloglomerular feedback (TGF) responses were studied in rats treated with antithymocyte rabbit serum (ATS). Microscopic findings revealed extensive mesangial cell loss and injury, enlarged capillary lumen, and decreased tortuosity of glomerular capillaries. Whole kidney GFR and SNGFR were lower in ATS-treated rats than in control rats (1.04 +/- 0.04 vs 0.94 +/- 0.03 ml/min/g kidney weight, 32 +/- 2 vs 27 +/- 1 nl/min, respectively) due to a decrease in Kf (0.017 +/- 0.001 vs 0.021 +/- 0.001 nl/s/mmHg). The magnitude of the TGF responses of SNGFR was less in ATS rats than in control rats (17% +/- 4% vs 34% +/- 5%), but that of SFP was not significantly different (18% +/- 2% vs 23% +/- 1%). These results indicate that the mesangial cells are necessary for full expression of the TGF mechanism and suggest the involvement of changes in Kf in the TGF mechanism. PMID- 1881035 TI - Endothelin effects on renal function and tubuloglomerular feedback. AB - Analysis of our data in conjunction with other recent literature allows the following conclusions regarding the role of endothelin in the tubuloglomerular feedback control mechanism and in the pathogenesis of acute ischemic renal failure: (1) Endothelin reduces nephron filtration rate in the nephrons with interrupted signal perception at the macula densa, in accord with preglomerular arteriolar constriction. Yet, the increase in filtration fraction in the whole kidney clearance study suggests a preferential postglomerular arteriolar constriction. Taken together, endothelin, which is a very potent renal vasoconstrictor, seems to constrict both preglomerular and postglomerular arterioles with a predominant constriction of the latter at the doses employed. (2) The endothelin-induced natriuresis is due to a fall in tubular reabsorption, reflecting a direct tubular action, possibly related to an elevation in blood pressure. (3) At the doses of endothelin used and under the present experimental conditions, changes in the magnitude of tubuloglomerular feedback (TGF) response or the feedback characteristic could not be detected. (4) No evidence was found for a participation of endothelin in the pathogenesis of acute postischemic renal failure, as evidenced by the absence of an improvement in glomerular filtration after treatment with endothelin antiserum. PMID- 1881036 TI - Sodium and potassium load in the loop of Henle, measured with intact and blocked tubuloglomerular feedback mechanism in juxtamedullary nephrons. AB - For the juxtamedullary nephrons only the loop of Henle is easily accessible for micropuncture. We have shown that the tubuloglomerular feedback (TGF) mechanism is highly activated in these nephrons. Techniques have been developed for measurements on these nephrons without disrupting the normal flow to the macula densa. The tubular flow rate was measured by a real-time videodensitometric method in juxtamedullary nephrons in Lewis x DA rats. For the determination of tubular fluid composition a small fraction (less than 10%) of the fluid was sampled. Measurements were also performed according to the conventional technique, where all the tubular fluid was sampled. Despite a more than twofold increase in tubular flow rate when the flow to the macula densa region was interrupted, sodium concentration was only reduced by 25%, whereas potassium concentration was reduced by 40%. The results demonstrate that interruption of the urine flow to the macula densa results in a 52% increase in the tubular load of Na in the loop of Henle of juxtamedullary nephrons, and a corresponding increase of 24% for K. Thus, TGF exerts a strong influence on these nephrons which is why previous data on water and electrolyte loads, based on stop-flow measurements, greatly overestimate these loads. PMID- 1881037 TI - Adenosine mediates tubuloglomerular feedback response: an element of metabolic control of kidney function. AB - Numerous studies have shown during the past 10 years that adenosine is present in the normoxic kidney and accumulates when ATP hydrolysis prevails over ATP synthesis. Local generation of adenosine by the macula densa cells and its release into the interstitium of the juxtaglomerular apparatus (JGA) is considered to be the link between the enhanced NaCl concentration in the tubular fluid and the subsequent responses including preglomerular vasoconstriction and reduction of renin release by the juxtaglomerular cells. Micropuncture and microperfusion experiments using specific adenosine agonists and antagonists support the concept that adenosine functions as a mediator in the signal transmission of the JGA. PMID- 1881038 TI - Role of proximal tubular reabsorption for the intrarenal control of GFR. PMID- 1881039 TI - Chronic dietary salt loading: resetting of tubuloglomerular feedback control of renal hemodynamics by an adrenal hormone. AB - Experiments were performed in chronically salt loaded rats (4 g% NaCl diet for 2 weeks) to determine whether the resetting of tubuloglomerular feedback (TGF) by a humoral inhibitor in tubular fluid is caused by a humoral factor from the adrenal glands. TGF response was assessed by measuring NGFR in the absence of loop of Henle perfusion and during perfusion at 40 nl/min with tubular fluid from normal or salt loaded rats and expressed as NGFR40/NGFR0. (1) Loop of Henle perfusion with tubular fluid from normal rats elicited a TGF response of 50.3% +/- 7.9% (mean +/- SEM) in normal rats and 57.2% +/- 7.9% in salt loaded rats. With tubular fluid from high salt rats, TGF response in normal rats was 97.4% +/- 6.3% and in salt loaded rats 98.0% +/- 1.6%. Participation of adrenal steroids in the inhibition is suggested by the following results: (2) Acute adrenalectomy (ADX) in high salt rats abolished the TGF inhibitory potency of high salt tubular fluid. TGF response in salt loaded rats with high salt tubular fluid from high salt ADX rats was 62.3% +/- 3.0%. Substitution of high salt ADX rats with matching adrenal venous blood from high salt rats restored TGF inhibition. (3) With cross over experiments the effect of heterologous adrenal venous blood substitution on TGF inhibitory activity was studied. The TGF response in high salt rats with high salt tubular fluid and tubular fluid from normal ADX rats substituted with adrenal venous blood collected from high salt rats was 88.9% +/- 5.5% and 91.7% +/- 6.0%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881040 TI - Hyperreactivity of tubuloglomerular feedback in chronically salt-loaded spontaneous hypertensive rats. AB - In order to investigate the mechanisms of the hyperreactivity of the tubuloglomerular feedback (TGF) mechanism in spontaneous hypertensive rats (SHR) the resetting of TGF by chronic dietary NaCl loading was studied in SHR and normotensive Wistar Kyoto rats (WKY). This treatment is known to reset the TGF by an inhibitory factor in tubular fluid and not by alterations of the intrinsic characteristics of the juxtaglomerular apparatus (JGA). TGF reactivity, and its resetting, were determined by loop of Henle perfusion with artificial late proximal tubular fluid and with harvested endogenous tubular fluid respectively. Dietary effects of the high sodium intake were measured by means of the systolic blood pressure (SBP), plasma volume (PV), and renal sodium excretion. The 4-week dietary treatment had no significant influence on SBP in WKY, whereas it accelerated the rise of SBP in SHR significantly. After 1 week of treatment, PV was increased in both WKY and SHR as compared with the control groups kept on the normal diet. Whereas PV in WKY declined to control values over the next 3 weeks, SHR remained expanded. GFR was similar in all groups, whereas urinary sodium excretion was significantly increased in salt-loaded SHR and WKY. Dietary salt loading was paralleled by the appearance of a TGF-inhibiting substance in the tubular fluid in SHR and WKY. However, when assayed with artificial late proximal tubular fluid, hyperreactivity was similar in normal and salt-loaded SHR as compared with WKY. Thus, in SHR TGF hyperreactivity is maintained in spite of volume expansion and TGF resetting by a humoral factor in tubular fluid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881041 TI - Tubuloglomerular feedback resetting in different models of acute volume expansion. AB - Our results revealed that renal blood flow (RBF) increased during both isooncotic and hypooncotic plasma expansion by 4% of body weight (BW). Tubuloglomerular feedback (TGF) sensitivity assessed by the measurement of proximal stop-flow pressure at loop perfusion rates of 0 to 40 nl/min and RBF autoregulation were not substantially affected by this degree of volume expansion, provided plasma oncotic pressure did not change. This upward shift of the TGF response curve together with maintenance of an RBF autoregulation during plasma expansion lead to the conclusion that the TGF mechanism apparently plays a significant role in the control of glomerular hemodynamics, despite the marked vasodilation occurring during acute volume expansion. PMID- 1881042 TI - Mechanisms of renin release from juxtaglomerular cells. AB - In microdissected, nonperfused afferent arterioles changes in intravascular pressure did not affect renin secretion. On the contrary, renin release from isolated afferent arterioles perfused in a free-flow system has been reported to be sensitive to simultaneous changes in luminal pressure and flow. Hence local blood flow may be involved in the baroreceptor control of renin release. If flow is sensed, the sensor is likely to be located near the endothelial cell layer, where ion channels have been shown to be influenced by variations in shear stress. PMID- 1881043 TI - Branching and confluence pattern of glomerular arterioles in the rat. AB - In addition to the usual division of the glomerular tuft into lobules, a subdivision into an afferent and an efferent capillary domain is made. Immediately after entering the glomerulus the afferent arteriole splits into superficially located branches which supply the lobules. The capillaries of each lobule first run towards the urinary pole; these parts of each lobule establish the afferent domain. The capillaries of each lobule running back towards the vascular pole establish the efferent domain. The afferent domain represents the major part of the tuft; it has the shape of an incomplete globe with a deep depression on one side within which the efferent domain is situated. The efferent arteriole is established inside the glomerular tuft within the efferent capillary domain. Generally tributaries from each lobule converge to form the intraglomerular segment of the efferent arteriole, which leaves the tuft by passing through the mesangium of the glomerular stalk. At this site the intraglomerular segment of the efferent arteriole is fully surrounded by the mesangium; consequently, it is exposed to the intramesangial pressure. PMID- 1881044 TI - Juxtaglomerular cells as a source of intrarenal angiotensin II production. AB - While the contribution of angiotensin (Ang) II to the regulation of various renal functions is recognized, evidence exists that the kidney also is a major site for the production of Ang II. Since circulating renin in plasma accounts for only a small portion of intrarenally produced Ang II, we investigated juxtaglomerular (JG) cells as a source of Ang I and II. Light and electronmicroscopic immunohistochemical methods revealed highly concentrated Ang I and II in JG cells. This finding was supported by the demonstration of colocalization of renin, Ang I, and Ang II in cultured JG cells and in dense granular fractions of rat kidney separated by gradient centrifugation of rat kidney homogenate. Perfusion of rat kidney with Krebs-Ringer buffer containing bovine serum albumin showed that Ang I and Ang II are released in the perfusate in quantities which may account for a greater part of the intrarenal generation of Ang II observed in vivo. These results support the hypothesis that Ang II is intrarenally synthesized inside the JG cells, thereby contributing to the regulation of certain renal functions. PMID- 1881045 TI - Application of polymerase chain reaction techniques to study of rabbit renin gene expression. AB - Studies were performed to develop techniques to assess renin mRNA in a single microdissected juxtaglomerular apparatus (JGA) of rabbit using the polymerase chain reaction (PCR) method of amplification of cDNA sequences. In preliminary studies synthetic oligonucleotide primers corresponding to regions in the rat renin cDNA sequence, which are highly conserved between mouse, rat, and man, were found to yield good amplification efficiency with a rat renin cDNA template, but little product was observed with rabbit cDNA template. We therefore employed a nested primer PCR cloning technique to clone an 839 base pair portion of the rabbit renin cDNA to obtain species-specific sequence information for primer design. Here we report the nucleotide sequence of a partial rabbit renin cDNA clone and the use of species-specific primers that permit semiquantitative assessment of rabbit mRNA levels in the single JGA. PMID- 1881046 TI - Cyclosporine and the renin-angiotensin system. AB - Much is known about the renin-angiotensin system during cyclosporine treatment: plasma renin or prorenin activity seems to be raised in man and animals; hyperplasia of the juxtaglomerular apparatus has been reported in man and animals; renin concentration is known to be increased in animal kidneys; renin angiotensin-like alterations in vascular contractility have been identified in animal vessels. Since the major functional side effects of cyclosporine are systemic vasoconstriction and renal vasoconstriction, the renin-angiotensin system could be involved. Also, an infrequent complication in man, vasculopathy, develops only in the afferent arteriole, where renin production is most abundant. Hence, this information is now reviewed and incorporated into a single pathophysiological concept, with the implication that renin activation plays a central role in the pathogenesis of cyclosporine-induced functional and structural lesions, merits further attention. PMID- 1881047 TI - Potential role for local luminal angiotensin II in proximal tubule sodium transport. AB - As a target site for angiotensin II (A-II), renal proximal tubule is unique in that it may be equipped with a local A-II generating system and that both basolateral and apical membranes may be accessible for the action of A-II. We have recently conducted studies to examine these possibilities. With in vitro cultured proximal tubular cells, we have demonstrated de novo synthesis of angiotensinogen and renin. With isolated renal brush border membrane (BBM), we have confirmed the presence of A-II receptors and found that A-II directly stimulated BBM Na+/H+ exchange. In search of the signal transduction mechanism, we have found that A-II also activated BBM phospholipase A2 (PLA) and that BBM contained a pertussis toxin-sensitive guanine nucleotide binding protein (G protein) which mediates the effects of A-II. Further studies showed that prevention of PLA activation abolished the effect of A-II on Na+/H+ exchange, and that activation of PLA by mellitin and the addition of arachidonic acid similarly enhanced BBM Na+/H+ exchange activity, suggesting that PLA activation may mediate the stimulatory effect of A-II on BBM Na+/H+ exchange. These results thus indicate that a local signal transduction mechanism involving G-protein mediated PLA activation exists in renal BBM which mediates the effect of A-II on Na+/H+ exchange. Taken together, we propose that, independent of A-II in the circulation, local luminal A-II may serve as an important regulatory system on sodium transport in renal proximal tubule. PMID- 1881048 TI - Macula densa cell function. AB - Studies concerning the sensing step in the tubuloglomerular feedback (TGF) mechanism have been conflicting. To study this step, we measured macula densa (MD) cell volume and membrane potentials in the isolated perfused ascending limb of the loop of Henle with attached glomerulus with MD segments (cTAL-MD). Addition of furosemide reduced cell volume rapidly and the effect could be reversed on removal of the drug. From the time course of cell volume changes hydraulic conductivity could be measured both in the basolateral and apical cell membrane. It was found that the apical cell membrane constituted the main barrier for water flow with a low hydraulic conductance, while the basolateral hydraulic conductance was quite high. Measurements of the basolateral electrical potential in the MD cells have shown a mean electrical potential of -56 mV. This potential was hyperpolarized by the addition of furosemide, the Cl channel blocker NPPB, or during a reduction of luminal NaCl from 150 to 30 mM, and depolarized when bath Cl concentration was reduced from 150 to 30 mM. These results are consistent with the following model for electrolytes transported and similar to the one described in the cTAL [15]. In the luminal cell membrane there is an Na-K-2Cl cotransporter that takes these ions into the MD cells and there is a potassium recycling through a K channel. On the basolateral membrane side there is an Na-K pump and a Cl channel through which chloride is transported out of the MD cell. The Na-K pump activity seems to be only 1/40 of that in the cTAL cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881049 TI - Communication of the tubuloglomerular feedback signal in the JGA. PMID- 1881050 TI - Chloride concentration in macula densa and cortical thick ascending limb cells. AB - The Cl- transport through the macula densa (MD) cells is believed to be a link in the tubuloglomerular feedback (TGF) believed to be a link in the tubuloglomerular feedback (TGF) mechanism and MD-mediated renin release. One step in this transport is probably the electroneutral and furosemide-sensitive Na(+)-K(+)-2Cl- contransport on the luminal membrane of MD cells. Another step is transport through basolateral Cl- channels. In the present study the intracellular Cl- concentration, [Cl-]i, was measured in the MD and cortical thick ascending limb (cTAL) cells, and the concentration changes elicited by blocking the Na(+)-K(+) 2Cl- cotransport with furosemide or by lowering the luminal NaCl concentration determined. We also investigated the effects of blocking the basolateral Cl- channels. A preparation consisting of a segment of the cTAL, MD cells, and the attached glomerulus was dissected from rabbit kidneys. The preparation was loaded with the Cl(-)-sensitive fluorophore SPQ, and perfused by using the isolated and perfused tubule technique. The intracellular chloride concentration was determined with a video system using digital imaging that measured the intensity of the emitted SPQ fluorescence. The T 1/2 of the leakage of SPQ was found to be (197 +/- 60) min (n = 9). With 150 mM NaCl in the lumen and bath, [Cl-]i in MD cells was 47 +/- 13 mM (n = 8) and 54 +/- 13 mM (n = 5) in cTAL cells. When furosemide (10(-4) M) was added to the luminal perfusion, the MD cell [Cl-]i was reduced to 6 +/- 2 mM. The corresponding value in cTAL cells was 5 +/- 3 mM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881051 TI - Optical studies on the action of furosemide on macula densa and cortical thick ascending limb cells. Intracellular calcium fluorescence measurements. AB - The present study shows the successful use of an optical technique that describes the application of both differential interference contrast (DIC) and fluorescence microscopy to the study of structure-function relationships in isolated perfused cTAL-MD segments of the nephron. Image-intensified video microscopy and digital image processing techniques were used to simultaneously and directly visualize and quantify [Ca+2]i in individual cTAL cells and MD cells. This study also indicates that no large changes in MD [Ca+2]i can be observed under maneuvers that are known to affect the autoregulatory mechanisms of single nephron glomerular filtration rate. Therefore, it is less likely that MD [Ca+2]i could be a link in the transmission of the signal from the MD cells to the rest of the cells in the juxtaglomerular apparatus for the release of the TGF mechanism and/or renin. Possibly some other mechanism like the electrolyte transport itself, that can alter the solute concentration and tonicity of the Goormaghtigh cell field (juxtaglomerular interstitium), may be the signal to proceed with the rest of the events developed by the juxtaglomerular apparatus to control single nephron glomerular filtration rate. PMID- 1881052 TI - Transport pathways in macula densa cells. PMID- 1881053 TI - Mesangial cell function and chloride ions. PMID- 1881054 TI - Tubuloglomerular feedback and chloride activity in the juxtaglomerular interstitium in Amphiuma. AB - Fresh-water animals excrete large volumes of dilute urine. The pronounced dilution of the tubular fluid starts in the early distal tubule. In this paper the reabsorptive capacity of the diluting segment is discussed, with special attention to the maximal salt concentration of the reabsorbed fluid. Earlier studies have shown a reabsorption-dependent chloride concentration on the basolateral side of the epithelium (juxtaglomerular interstitium, JGI) at the site of the juxtaglomerular apparatus. In the present study measurements were made of chloride activities in the immediate vicinity of the basolateral side of the tubular epithelial cells at high and low tubular perfusion rates. Extremely high chloride activities (2451 +/- 625 mM (SE), n = 7) were found in the JGI at maximal reabsorption, while more plasma-like values were noted at zero tubular flow. The flow-dependent salt reabsorption may be a powerful signal for tubuloglomerular feedback from the tubular lumen to the effector cells. PMID- 1881055 TI - Role of the efferent arteriole in tubuloglomerular feedback. AB - Tubuloglomerular feedback (TGF) is generally regarded as being mediated by a single, humoral vasoconstrictor acting on the afferent arteriole. Examination of the literature reveals, however, that acute activation or blockade of TGF may, under certain circumstances, be associated with vasomotion of the efferent arteriole, either in the same or in the opposite direction as the afferent arteriole. The former appears to be the case particularly when myogenic autoregulation is attenuated, for example, with application of calcium channel blockers. Experiments in which the TGF signal is chronically lost by preventing tubular fluid flow at the macula densa also suggest participation of the efferent arteriole. Under these circumstances, stop flow pressure and single nephron filtration rate increase and glomerular blood flow falls. TGF activity at this stage is modestly enhanced. Taken together, these findings suggest efferent vasoconstriction. After a delay of some hours, vasoconstriction is also apparent in the afferent arteriole. It is not clear whether the mechanism involved in this response is related to the "normal" TGF response. Together, these findings are hard to reconcile with the hypothesis of a single vasoconstrictor acting on the afferent arteriole. PMID- 1881056 TI - The afferent arteriole--the target for macula densa-generated signals. AB - The contractile characteristics of the afferent arteriole revealed in the present series of experiments lead one to predict that TGF-induced vasoconstriction should be dependent on both A-II and adenosine. In fact, previous evidence has suggested a role for both adenosine and angiotensin in the TGF mechanism. Acceleration of adenosine deamination as well as adenosine receptor blockade markedly reduced the effect of distal NaCl concentration on SNGFR or PSF. Conversely, inhibition of adenosine breakdown or cellular adenosine uptake, two interventions which are likely to increase interstitial adenosine levels, augmented TGF responses. The same effect was seen when adenosine1-receptor analogs were locally applied by microinfusion. The administration of A-II converting-enzyme blockers or A-II-receptor antagonists reduced TGF responses, while peritubular or intravenous administration of A-II augmented them. Furthermore, the inhibition of TGF responses caused by volume expansion-induced reductions in plasma A-II concentrations could be restored to normal by A-II infusion. The present results raise the possibility that normal TGF responsiveness depends upon the availability of both adenosine and A-II in sufficiently high concentrations. Figure 1 outlines a mechanism of this mutual dependency. One may assume that adenosine is generated as a consequence of NaCl dependent changes in NaCl transport by macula densa cells or by TALH cells in the immediate vicinity of the macula densa. The absence of capillaries in the juxtaglomerular interstitium could permit an accumulation of the autacoid to an extent not possible in other regions of the renal interstitium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881057 TI - Communication between the macula densa cells and the afferent arteriole. PMID- 1881058 TI - Macula densa control of glomerular hemodynamics. PMID- 1881059 TI - Direct action of vasoactive substances on isolated canine superficial and juxtamedullary afferent arterioles. PMID- 1881060 TI - Determinants of renal microvascular autoregulatory behavior in normal and hypertensive rats. PMID- 1881061 TI - Morphological characterization of human juxtaglomerular apparatus. AB - The recent demonstration of the endothelial fenestration at the juxtaglomerular part of the afferent arteriole facing mesangial and granular cells and finger like protrusions of urinary space into the region of the lacis in experimental animals like the rat, the mouse, and Tupaia belangeri led us to propose the hypothesis of a "short loop" feedback mechanism. To establish whether a further species possesses these morphological features, the JGA region was examined in the human kidney. Tissue was obtained by needle biopsy from patients and conventional electron-microscopical procedures including serial sections were utilized to reevaluate the morphology of JGA. Both the endothelial fenestration in the wall of the afferent arteriole and protrusions with filtration slits of urinary space into the lacis, were observed with remarkable heterogeneity. The occurrence of these features of JGA in such diverse mammalian species as rat, mouse, Tupaia, and man suggests that these structures may be involved in regulatory process and the proposed "short loop" feedback mechanism may be a general phenomenon. PMID- 1881062 TI - Oscillations and more complex dynamics in tubuloglomerular feedback. PMID- 1881063 TI - Dynamics of renal blood flow autoregulation in rats. AB - Two separate components could be resolved in tests of the dynamic autoregulation of renal blood flow. The slow component corresponds to the frequency at which spontaneous proximal tubular pressure oscillations are found, and are most likely due to the operation of the TGF. The high frequency component most likely represents an intrinsic vascular, myogenic, mechanism. The gain maximum of the admittance in the frequency range corresponding to the autonomous tubular oscillations indicates that the dynamic characteristics responsible for the occurrence of the spontaneous tubular oscillations must be common to a significant fraction of the total nephron population. PMID- 1881064 TI - [Surgical treatment of acute intestinal obstruction]. AB - The experience with treatment of acute ileus for the 5 years in 1032 patients is summarized. Operated on were 269 patients. The different types of operative interventions with a wide use of intubation, adsorbents, laparostomy were performed. The postoperative lethality was 9.2%. PMID- 1881065 TI - [Disorders of the immune status and hematopoiesis in suppurative peritonitis and their correction with the preparation "Antilympholin"]. AB - In patients with purulent peritonitis, the severe immunodepression and suppression of proliferative activity of stem elements of hemopoietic tissue stroma were revealed. The effectiveness of the use as an immunomodulator of the preparation "Antilympholin" which has the marked immunostimulating properties is shown. PMID- 1881066 TI - [Radical operation--a method of its selection in perforated gastroduodenal ulcer]. PMID- 1881067 TI - [Diagnosis and the results of surgical treatment of perforated gastroduodenal ulcers]. AB - The results of treatment of 438 patients with a perforating gastric and duodenal ulcer are presented. The use of emergency +gastroduodenal fibroscopy for early diagnosis permitted to reduce the incidence of diagnostic errors from 7.1% to 0. The indications for different types of operations have been established. Of the methods for gastric resection, a method with creation of +terminal-lateral +gastroduodenal anastomosis developed in the clinic is preferable. The excellent and good long-term results after closure of a perforative hole were noted in 11.7% of the patients, after vagotomy--in 91.6% after gastric resection--in 88%. PMID- 1881068 TI - [Indications for creating inter-intestinal anastomosis in peritonitis with regard to the status of regional blood flow]. PMID- 1881069 TI - [Use of polymer materials in the complex treatment of experimental peritonitis]. PMID- 1881070 TI - [Ultrastructural changes in neutrophils and anaerobic microorganisms during their interactions in experimental acute intestinal obstruction]. AB - The authors established that 12 h after development of acute obstructive ileus in inactive neutrophil granulocytes (NG), the anaerobic microorganisms were intact, or at the process of division; in the active NG, they were destroyed, or when forming "halo", might preserve and migrate in the matrix of NG. In interaction of NG with microorganisms, the numerous oval and roundish bacterial bodies with a diameter of 0.2-0.5 micron capable to penetrate into the non-phagocytic cells are formed. A function of the formations revealed is not studied. PMID- 1881071 TI - [Elective relaparotomy as a method of treatment and prevention of complications of diffuse suppurative peritonitis]. AB - The results of treatment of 41 patient with diffuse purulent peritonitis, who underwent 2 and more relaparotomies are analysed. It has been proved that performance of the elective relaparotomy for preventing the development of intraabdominal complications of peritonitis were superior to the existing methods of treatment. It permitted to reduce lethality in diffuse purulent peritonitis 3.6-fold. PMID- 1881072 TI - [Use of external drainage of the thoracic duct and lymphosorption in the complex treatment of acute diffuse peritonitis]. AB - In 47 patients with acute generalized peritonitis in the complex of therapeutic measures, the external drainage of the thoracic duct (EDTD) with subsequent lymphosorption (LS) was used. The effectiveness of treatment was judged about by the lymph and blood toxicity, and as well by contents of peptides with the molecular mass of from 300 to 1000 dalton. In favourable course of the postoperative period, the increase in lymph debit and decrease in proteolytic enzyme activity in the lymph and blood were noted. The use of EDTD and LS in the complex with the other methods of treatment permitted to achieve a clinical effect in 76.6% of cases. PMID- 1881073 TI - [Clinico-roentgenological symptoms of acute adhesive intestinal obstruction]. AB - The clinico-roentgenological signs of acute commissural ileus were analysed in 226 patients. Of them, 192 were operated on. In 6.4% of the patients in plain roentgenography, the signs of acute ileus were absent, in 27.7%--they were not prominent. Study of the barium suspension passage through the small intestine, as the authors consider, is indicated in unmarked clinical features of the disease, and as well in its short duration (less than 6 h) with the aim of establishing a degree of ileus (complete, or partial). PMID- 1881074 TI - [Incidence of development and the results of treatment of post- operative peritonitis]. AB - In the clinic at the period of from 1977 to 1987 after 13,006 operations on the abdominal organs, 185 patients (1.4%) ranging in age from 16 to 89 years developed peritonitis. The lethality after relaparotomy performed within the first 24 hours of the complication development was 15.9%, later on--73.7%. In spite of the large extent and trauma of radical relaparotomy, the lethality after it was 56%, after palliative one--90%. Timely is the performance of relaparotomy within the first 6 h from the moment of the complication development, in prolongation of the time to 7-12 h, the lethality was 12.5%. PMID- 1881075 TI - [Evaluation of the effectiveness of detoxicating plasmapheresis in acute surgical diseases of the abdominal organs]. PMID- 1881076 TI - [Surgical treatment of closed abdominal injuries]. AB - The experience with diagnosis and treatment of closed abdominal injuries in a specialized department of polytrauma for 3 years is summarized. The diagnostic and surgical tactics in given pathology consisting in early diagnosis of possible injuries to the viscera and emergency operative intervention is presented. PMID- 1881077 TI - [Postoperative hemorrhage in abdominal injuries]. AB - The experience with treatment of 19 sufferers with abdominal trauma, who underwent relaparotomy for postoperative hemorrhage is summarized. The most informative tests permitting to establish the indications for relaparotomy, medical errors leading to relaparotomy, causes of death are presented. PMID- 1881078 TI - [Non-cancerous tumors of the stomach and duodenum as a cause of acute hemorrhage]. PMID- 1881079 TI - [Atypical methods of surgical arrest of profuse gastric hemorrhage]. AB - The methods for arrest of profuse gastric hemorrhage in difficult situations aimed at life salvage of a patient, prevention of the postoperative complications are suggested. Knowledge of the non-conventional methods for arrest of hemorrhage will be of an essential help to a practical physician. PMID- 1881080 TI - [Surgical treatment of hemorrhage from acute gastric ulcers and erosions]. AB - On the basis of analysis of operative treatment of 229 patients with hemorrhage from acute gastric ulcers and erosions, the advantages of vagotomy (68 cases) over the other types of operations (stitching of ulcers--102, devascularization of the stomach--48, resection of the stomach--11) are shown. Decrease in incidence of postoperative recurrencies of hemorrhage, and comparatively low lethality permit to recommend vagotomy with pyloroplasty as an operation of choice in acute erosive-ulcerous lesions of gastric mucosa. PMID- 1881081 TI - [Principles of complex treatment of infection in emergency surgery]. AB - The analysis of 140 cases of acute surgical sepsis is presented. The general principles for the treatment of sepsis in emergency surgery were established. The most effective are the guided laparotomy in peritoneal sepsis, use of intravascular laser blood irradiation, chemotherapeutical means and dressing materials (polysorb, carboserix, collocyl etc.), different gaseous media (aeroionotherapy, oxygenation, ozonized guided antibacterial medium) which have favourable effect on the reparative processes in the primary foci of infection. Resulting from the use of complex treatment, the decrease in lethality from 75 to 35.7% was noted. PMID- 1881082 TI - [Surgical tactics in complicated forms of acute cholecystitis]. AB - The analysis of the results of surgical treatment of 223 patients with complicated forms of acute cholecystitis was carried out. Resulting from complex examination, the correct preoperative diagnosis was established in 93% of patients, in 7%--the character of complications was revealed at operation. Surgical treatment was aimed at adequate correction of all the complications revealed. PMID- 1881083 TI - [Acute cholecystitis in the early postoperative period]. AB - The authors observed 6 patients, who developed acute cholecystitis at day 2--5 after the operation. In 3 patients, an operation on the abdominal organs was performed, in 3--the urologic intervention. The leading symptoms of postoperative cholecystitis are the following: epigastric pain, stable intestinal paresis, high body temperature. The authors recommend a wide use of the ultrasound investigation of the abdominal cavity, and in its negative results, or in absence of the apparatus--laparoscopy. All the patients were reoperated. One patient died. PMID- 1881084 TI - [Diagnosis and treatment of stenosis of the major duodenal papilla after cholecystectomy]. AB - The data of diagnosis and treatment of 59 patients with stenosis of the major duodenal papilla (MDP) revealed at different periods after cholecystectomy are analysed. In diagnosis of MDP stenosis, the following methods were employed: ultrasounds scanning of the liver and bile ducts, intravenous cholangiography, endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography. The surgical method of treatment was used in 24, an endoscopic method--in 28, a combined one--in 7 patients. The indications and contraindications for the use of different methods of treatment are presented. It is noted that the use of a complex of modern methods of diagnosis and treatment will permit to establish precisely MDP stenosis after previously performed cholecystectomy and eliminate it with minimal lethality. PMID- 1881085 TI - [Classification of suppurative forms of peritonitis]. PMID- 1881086 TI - [Serum gastrin level after surgical treatment of duodenal ulcer hemorrhage]. AB - The serum gastrin content in patients with ulcerous duodenal bleeding was studied in the process of surgical treatment. A significant decrease in the hormone concentration with increase in the volume of acute blood loss was noted. PMID- 1881087 TI - [Errors in establishing the indicators for cholecystectomy as a cause of development of post-cholecystectomy syndrome]. PMID- 1881088 TI - [Rare cause of acute obstruction of the afferent loop of gastro- enteroanastomosis after gastrectomy by the Billroth II method]. PMID- 1881089 TI - [Effect of endolymphatic antibiotic therapy on the status of cellular immunity in peritonitis]. AB - The immune status in 68 patients with diffuse and generalized peritonitis was studied. It was established, that a degree of the impairment in immune response depended on peritonitis spreading. Endolymphatic antibiotic therapy had immunostimulating effect in patients with diffuse peritonitis, in generalized peritonitis, this was not observed. In patients with generalized peritonitis, it is necessary to include into the complex of treatment the other methods of immunologic correction. PMID- 1881090 TI - [Gangrenous appendicitis complicated by perforation of acute duodenal ulcer]. PMID- 1881091 TI - [Perforation of duodenal ulcer simulating incarceration of postoperative ventral hernia]. PMID- 1881092 TI - [Acute gangrenous-perforative cholecystitis with rupture of the liver and intra abdominal hemorrhage]. PMID- 1881093 TI - [Perforation of the stomach with a probe]. PMID- 1881094 TI - [Femoral hernia complicated by incarceration of Meckel's diverticulum]. PMID- 1881095 TI - [Acute epiploitis simulating acute appendicitis]. PMID- 1881096 TI - [Rare cause of acute intestinal obstruction]. PMID- 1881097 TI - [Nursing standards--ways to quality assurance]. PMID- 1881098 TI - [New role in nursing--generalist nurse--necessity or utopia?]. PMID- 1881099 TI - [England on the path to "Health for all"]. PMID- 1881100 TI - [A study trip to Turkey]. PMID- 1881101 TI - [Children in armed conflicts]. PMID- 1881102 TI - [Many salaries in Switzerland are barely enough to live on. "We are living in a monetary illusion"]. PMID- 1881103 TI - [Aging: other viewpoints]. PMID- 1881104 TI - [Violent boarders...]. PMID- 1881105 TI - [Aggressive nurses]. PMID- 1881106 TI - [Managing aggression in a constructive way]. PMID- 1881107 TI - [Violence in the emergency services]. PMID- 1881108 TI - [Medicine and nursing--together or against each other? Professionalization furthers better cooperation]. PMID- 1881109 TI - [Current status and perspectives of the HoFa-professional training: role in practice]. PMID- 1881110 TI - [Civil service and the social year in the German Federal Republic: the nursing shortage is being intensified]. PMID- 1881111 TI - [Interview with Monika Muller-Angst on the use in nursing of civilian service workers. Learning by experiences in foreign countries. Interview by Fred Arm]. PMID- 1881113 TI - [Looking for employment with a personal cypher advertisement]. PMID- 1881112 TI - [Ozone load in Switzerland. No change of the trend in sight]. PMID- 1881114 TI - [Nursing diagnosis; a different aspect]. PMID- 1881115 TI - [Do children have to stay home during summer smog?]. PMID- 1881116 TI - [Looking for employment with the help of a personnel counselor]. PMID- 1881117 TI - Recognition of bacterial endotoxin in biologic systems. PMID- 1881118 TI - Structure and function of the endothelial cytoskeleton. PMID- 1881119 TI - Plasma lipopolysaccharide-deacylating activity (acyloxyacyl hydrolase) increases after lipopolysaccharide administration to rabbits. AB - Acyloxyacyl hydrolase (AOAH) is a leukocyte enzyme that removes secondary (acyloxyacyl-linked) acyl chains from the lipid A moiety of bacterial lipopolysaccharides (LPS). We now report that the same enzymatic activity is present in normal rabbit plasma and that its activity can be greatly increased by LPS challenge. Intravenous administration of LPS to rabbits resulted in a rapid increase (peaking at 90 minutes, with a mean peak increase of 16-fold) of plasma AOAH activity; the activity then slowly decreased to baseline levels over 24 hours. The plasma AOAH is probably derived, at least in part, from circulating leukocytes, since (a) the AOAH response was significantly diminished in leukopenic rabbits, and (b) incubation of blood or isolated leukocytes with LPS in vitro resulted in increased extracellular AOAH activity. These results indicate that AOAH can appear extracellularly, in plasma, as part of the early response to intravenous LPS challenge. The cellular source(s) and biological role of the plasma enzyme remain to be determined. PMID- 1881120 TI - Complement and monocytes are essential for provoking glomerular injury in passive Heymann nephritis in rats. Terminal complement components are not the sole mediators of proteinuria. AB - Complement but not polymorphonuclear granulocytes (PMN) causes glomerular injury in passive Heymann nephritis in rats. We have now identified monocytes as another important mediator in this model. Passive Heymann nephritis was induced in Wistar rats by intravenous injection of sheep anti-rat Fx1A antiserum. Four groups (all receiving anti-rat Fx1A antiserum) were studied: (a) rats given normal sheep globulin (nephritic controls), (b) rats given sheep anti-rat PMN globulin (PMN depleted), (c) rats given sheep anti-rat monocyte globulin (monocyte-depleted), (d) rats injected with cobra venom factor (complement-depleted). In vitro specificity controls for anti-cell antisera were made by cytotoxicity tests and inhibition of phagocytosis. In vivo specificity controls were performed in heterologous Masugi nephritis (PMN-dependent) and accelerated Masugi nephritis (monocyte-dependent). Complement and monocyte depletion significantly delayed the onset of proteinuria (p less than 0.001 versus nephritic controls on day 5), PMN depletion had no significant effect. Monocyte infiltration was seen in control nephritic rats, but monocyte depletion prevented this influx. In the monocyte depleted group, no differences in glomerular deposition of C3, C9, and C5b-9 were seen in comparison to the nephritic control rats. Serum C3 levels were comparable in groups a, b, and c, the complement system was biologically active in the monocyte depleted-group (c), and the amount of anti-Fx1A antibody bound was the same in all groups. This shows that, besides complement, monocytes are required for induction of renal damage in passive Heymann nephritis. The concept of a sole role for complement in glomerular immune injury involving subepithelial immune deposits should be reconsidered. PMID- 1881121 TI - Monoclonal antibodies to human embryonal carcinoma cells: antigenic relationships of germ cell tumors. AB - Fifteen monoclonal antibodies (mAb) that show specificity for human embryonal carcinoma cells are described. C57BL/6 mice were immunized with Tera-2 embryonal carcinoma cells, and hybridomas were isolated and tested versus a set of human developmental tumor cell lines. The antigens exhibit relatively restricted and unique distributions on normal tissues as shown by immunohistochemistry. The mAbs recognize a series of differentiation antigens since their expression changes when teratocarcinoma stem cells are induced to differentiate in vitro. The expression of these molecules in germ cell and related tumors is consistent with the data obtained from in vitro cell studies. Seven of these mAbs immunoprecipitate molecules from surface labeled Tera-2 cells that show distinct molecular weights on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The antigenic phenotypes defined by the set of mAbs can be used to investigate possible pathogenetic relationships of the various testicular tumors. PMID- 1881122 TI - Permeabilized hepatocyte couplets. Adenosine triphosphate-dependent bile canalicular contractions and a circumferential pericanalicular microfilament belt demonstrated. AB - The motility of bile canaliculi was examined in hepatocyte couplets permeabilized with palmitoyl lysophosphatidyl choline in a dosage regimen that drastically affected secretory function, yet maintained relative integrity of the cellular cytoskeleton. The permeabilized cells showed no exclusion of trypan blue, notable cytoplasmic organelle and membrane damage, and no uptake or secretion of either fluorescein diacetate or sodium fluorescein. However, bile canalicular structure remained relatively intact and actin and myosin were localized immunocytochemically in the pericanalicular region. Coincident with the administration of 1 mM ATP, 2 mM Mg2+, and 1 microM Ca2+, the canaliculi contracted with partial or complete luminal closure. ADP, AMP, or AMP-PCP could not be substituted for ATP. A dose-dependent relationship was shown between ATP concentration and canalicular contraction rate. The permeabilization procedure also provided enhanced visualization of pericanalicular microfilaments, believed to be actin filaments, and their organization into two layers: an inner membrane associated network, and an outer filament bundle that inserted into belt junctions (zonulae adherentes). The organization of the microfilament belt of contiguous hepatocytes was such that it formed a circumferential band of microfilaments around the canaliculus. It is analogous to contractile filament belts found in the apical terminal web region of other epithelia. It was also observed that with canalicular luminal closure, there was a change in the organization of the pericanalicular microfilaments. It is concluded that in hepatocyte couplets, differential sensitivity of cell components to permeabilization can be achieved with palmitoyl lysophosphatidyl choline. In addition, the results provide evidence that the bile canaliculus has the capacity to be a contractile structure even in the absence of secretion, that canalicular contraction is ATP-dependent, and hence is a dynamic process. PMID- 1881123 TI - Contractile cells in rat myocardial scar tissue. AB - In earlier studies of rat myocardial tissue reactions to necrotizing injuries, we observed in the resulting scar tissue a large number of smooth muscle cells unassociated with blood vessels. Since these cells are not normal components of ventricular myocardium, we studied the appearance and fate of all cells with smooth muscle-like features in healing and healed lesions at intervals up to 10 weeks after ischemic or freeze-thaw injuries. Observations were made with light and electron microscopes, using conventional methods and immunostaining methods to detect alpha-smooth muscle actin. In healing and healed lesions, smooth muscle actin was detected histologically in capillary pericytes, myofibroblasts, and both vascular and nonvascular smooth muscle cells. Its association with cytoplasmic microfilaments in nonsarcomeric myocytoskeletal arrangements was confirmed ultrastructurally. The pericytes and myofibroblasts predominated during the earlier hypercellular healing period. The smooth muscle cells appeared near the end of the first week of repair; they were initially located mainly in presumptive vascular structures, identified by residual basal lamina sheaths, but subsequently located mainly in nonvascular locations. After the second week until the end of the study the number of nonvascular smooth muscle cells increased and that of myofibroblasts decreased. The nonvascular smooth muscle cells predominated in the larger mature scars, especially the transmural ones. From these observations, we have concluded that contractile cells other than cardiac myocytes have important roles in myocardial tissue repair, have suggested that their roles are related to the forces of myocardial contractions, and have discussed their possible functions and lineage interrelationships. PMID- 1881124 TI - Presence of type I and VI collagen mRNAs in endothelial cells in cutaneous neurofibromas. AB - In situ hybridization and peroxidase anti-peroxidase immunodetection were used in the same tissue sections to elucidate the spatial distribution of collagen gene expression in cutaneous neurofibromas, particularly in relation to blood vessels; the latter structures were identified by the presence of factor VIII-related antigen. The data indicate a clear relationship between the vascular structures and sites of locally elevated expression of type I and VI collagen genes. Specifically, some, but not all, blood vessels were surrounded by stromal cells highly active in expressing pro alpha 1(I) and alpha 2(VI) collagen genes. Furthermore, these genes were expressed by a subpopulation of endothelial cells within the walls of blood vessels traversing the lesion. To quantitate the overall expression of five genetically distinct collagen genes in cutaneous neurofibromas, we performed Northern analyses and slot blot hybridizations with pro alpha 1 (I), pro alpha 2 (I), pro alpha 1 (III), pro alpha 1 (IV) and alpha 2(VI) collagen cDNAs. Although the mRNA levels for all five genes were slightly increased in neurofibroma tissue, only the abundance of alpha 2(VI) collagen mRNAs was significantly elevated, as compared with normal skin. We conclude that endothelial cell populations with different levels of collagen gene expression exist within cutaneous neurofibromas: some are actively expressing type I and VI collagen genes, whereas in other the expression of these genes is effectively down-regulated. The markedly elevated steady-state levels of type VI collagen mRNAs suggest that synthesis of type VI collagen may contribute to the growth and architecture of cutaneous neurofibromas. PMID- 1881125 TI - Neuron-specific thresholds of aluminum toxicity in vitro. A comparative analysis of dissociated fetal rabbit hippocampal and motor neuron-enriched cultures. AB - Mature dissociated motor neuron-enriched and hippocampal neuron cultures derived from fetal New Zealand white rabbits were continuously exposed to 1, 10, 25, 50, or 100 microM AlCl3 in a chemically defined medium for 14 days. Motor neuron enriched cultures exposed to low concentrations (1 or 10 microM) of AlCl3 remained viable for the entire experiment but developed perikaryal and neuritic inclusions composed of phosphorylated neurofilament. Similar inclusions developed in cultures exposed to 25 and 50 microM AlCl3, but motor neurons did not survive beyond 10 days exposure. The 100 microM AlCl3-supplemented medium induced cell death within 72 hours without development of inclusions. In contrast, hippocampal neurons exposed to 1, 10, or 25 microM AlCl3 developed no morphological changes or inclusions. Although hippocampal cultures exposed to 50 or 100 microM AlCl3 developed perinuclear and proximal neuritic inclusions of phosphorylated neurofilament after 10 days, they remained viable. These in vitro morphological observations demonstrate a 10-fold greater sensitivity of spinal motor neurons to aluminum toxicity when compared with hippocampal neurons and suggest that the earlier observations of neuron-specific thresholds of aluminum toxicity in vivo are related to unique regulatory mechanisms of neurofilament biosynthesis and catabolism within distinct neuronal cell populations. PMID- 1881126 TI - Carbon stripping extracts serum free fatty acids: implications for media supplementation of cultured type II pneumocytes. AB - Carbon stripping is a process that is widely used to remove hormones from serum. Because addition of serum to culture media also provides exogenous fatty acids that influence lipid metabolism of cultured cells, we investigated the effects of carbon stripping on the composition of the phospholipid and free fatty acid fractions in fetal bovine serum and the effects of these changes on phosphatidylcholine synthesis by cultured adult alveolar type II cells. Carbon stripping resulted in quantitative and qualitative changes in serum free fatty acids. The process effectively extracted greater than or equal to 99% free fatty acids and, to a lesser extent, phospholipids. There were also qualitative changes in the relative composition of the remaining free fatty acids with a selective loss of oleic and linoleic free fatty acids. However, the relative composition of the serum phospholipid fatty acid fraction was unaffected. Type II cells isolated from adult male rat lung and cultured in Dulbecco's modified Eagle's medium supplemented with 10% carbon-stripped fetal bovine serum (FBS-CS) incorporated [3H]choline into phosphatidylcholine at a rate 36% less than the rate of control cells cultured with unstripped FBS. Addition of oleic acid to FBS-CS supplemented media increased total phosphatidylcholine synthesis by adult type II cells by 67 71%. In contrast, addition of palmitic acid inhibited PC synthesis 51-67%. The combination of oleic and palmitic acids resulted in a rate of [3H]choline incorporation into phosphatidylcholine similar to the rate for control cells cultured in FBS-CS-supplemented media alone. Although synthesis of disaturated phosphatidylcholine was unaffected by exogenous fatty acids, addition of fatty acids altered the proportion of disaturated phosphatidylcholine synthesis relative to total phosphatidylcholine synthesis. The presence or absence of the hormones, dexamethasone and triiodothyronine, did not explain the difference in rate of phospholipid synthesis by type II cells cultured in untreated versus carbon-stripped serum supplemented media. These results suggest that the removal of serum free fatty acids by carbon stripping can influence phospholipid metabolism of cultured type II cells. Because serum free fatty acids influence cellular lipid composition and potentially cell metabolic functions, carbon stripped serum may not be the optimal choice for media supplementation of cultured cells. PMID- 1881127 TI - Totalitarianism and fatalistic suicide. PMID- 1881128 TI - Observer hypercompetitiveness and victim precipitation of rape. PMID- 1881129 TI - Perceptions of a known rape victim: role of subject's gender and personal experience with rape. PMID- 1881130 TI - Courtesy stigma: the social implications of associating with a gay person. AB - We investigated the operation of courtesy stigma with American male college students who reacted to a fictitious male student described as gay, rooming by choice with a gay male student, involuntarily assigned to room with a gay, or rooming with a male heterosexual. Among respondents who expressed strong intolerance of gays, the voluntary associate of a gay was perceived as having homosexual tendencies and as possessing the same stereotyped personality traits attributed to a gay. No such courtesy stigma was attached to the involuntary associate of a gay by these respondents. Relatively tolerant respondents engaged in no courtesy stigmatization at all. Thus, courtesy stigmatization occurred only under circumscribed conditions and appeared to depend more on the tendency of highly intolerant individuals to infer that a male student who apparently liked a gay individual was himself gay than on a motivation to maintain cognitive consistency. PMID- 1881131 TI - Angiotensin II increases portosystemic collateral resistance in portal hypertension. AB - The decreased vasoconstrictive response of the splanchnic vasculature in portal hypertension (PHT) to angiotensin II (ANGII) is newly established. This could explain the limited ability of PHT patients to compensate in hypovolemic shock. However, the effect of ANGII upon portosystemic collateral resistance (Rc) is not known. We hypothesized that ANGII could directly effect Rc and thus change portal venous pressure (PVP). Chronic PHT was induced in New Zealand white rabbits by partial portal vein ligation 3 weeks prior to study. Splanchnic blood flow and portosystemic shunt (PSS) were measured simultaneously in six normal rabbits and then in six PHT rabbits at baseline and during intravenous ANGII infusion at 1.0 microgram/kg/min. Flow and resistance were standardized to 100 g small intestine weight. Superior mesenteric artery flow (Qsma) in normal rabbits was 64.9 +/- 3.6 ml/min, increased to 134.6 +/- 13.5 ml/min in the PHT animals (P less than 0.001) and was reduced 30% (P less than 0.05 vs PHT baseline) with ANGII. Concomitantly, PVP in the PHT animals was twice normal, 7.0 +/- 0.32 vs 14.4 +/- 0.55 mm Hg (P less than 0.001) and rose slightly with ANGII. The high PSS in PHT (84 +/- 6.0%, P less than 0.001 vs normal) was not affected significantly by ANGII infusion. Rc in the PHT rabbits rose 50% from 0.06 +/- 0.001 to 0.09 +/- 0.01 mm Hg/ml/min (P less than 0.001) with ANGII. This is the first evidence for a vasoconstrictive response in portosystemic collaterals during ANGII infusion. This change in collateral resistance causes both PVP and PSS to remain pathologically elevated in PHT despite a fall in portal inflow, thus predisposing to repeat variceal bleeding. PMID- 1881132 TI - Resident evaluation of surgical faculty. AB - This study examines the association between resident evaluations of surgical faculty and measures of teaching activity and practice characteristics. Twenty three of 33 general surgery residents, anonymously and voluntarily rated 62 faculty surgeons in 10 areas of performance. This was repeated 1 year later with 24 of 28 residents and 64 surgeons. Ratings were reliable (test-retest on overall mean rating, r = 0.91, P less than 0.01). Factor analysis of ratings by residents in postgraduate year (PGY) 5 extracted a judgment factor and an interpersonal skills factor. Ratings by other PGYs were unidimensional. Faculty subgroups that performed more than two major procedures per week at the hospital (P less than 0.01) attended the weekly Mortality and Morbidity conference more than once per month (P less than 0.05) and/or published one or more research reports (P less than 0.05) received higher ratings than those who did not. Among general surgeons (n = 35), ratings of interpersonal skill by PGY 5 residents correlated inversely with complication rate (r = -0.41, P less than 0.05) and overall ratings by PGYs 3 and 4 correlated inversely with mean patient length-of-stay (LOS; r = -0.44, P less than 0.05). These remained significant after statistical adjustment for case mix differences and differences in the amount of contact with residents. Resident ratings were unrelated to mean patient age, the mean number of diagnoses per patient, and the mean number of procedures per patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881133 TI - Elemental diet alters macrophage function in mice. AB - Administration of a chemically defined liquid elemental diet (ED) induces spontaneous bacterial translocation to mesenteric lymph nodes (MLN) in animal models. The influence of this process on host immunity is unclear. This study evaluated the effects of ED on peritoneal macrophage (PM phi) antimicrobial functions. Conventional C57/BL6 mice and endotoxin-resistant C3H/HeJ mice (n = 60) were randomized to be pair-fed either an ED or regular chow diet (RD) for 14 days. Blood, spleen, liver, and MLN were cultured for bacteria. PM phi were harvested for: percentage Candida albicans (CA) phagocytosis, percentage killing of CA, PM phi superoxide anion (O2-) production, and TNF-dependent macrophage cytotoxicity. Enteral feeding of ED in conventional C57/BL6 mice caused significant bacterial translocation to MLN but not other organs. Significant impairment of CA killing by PM phi occurred in the ED group and was associated with reduced O2- production. Tumor necrosis factor (TNF)-dependent cytotoxicity of PM phi was also decreased. In endotoxin-resistant C3H/HeJ mice, bacterial translocation was not observed and PM phi antifungal functions remained similar in both RD and ED groups. Thus, enteral feeding of an elemental diet downregulates host oxidative and antimicrobial mechanisms and TNF-dependent cytotoxicity in conventional mice which may be secondary to elemental diet induced bacterial translocation. PMID- 1881134 TI - Sensitized B lymphocytes contribute to acute allograft rejection. AB - The contribution of sensitized B lymphocytes to second-set allograft rejection has been relatively ignored despite their regular appearance in rejecting allografts. This study presents evidence that adoptively transferred sensitized B lymphocytes accelerate the rate of acute allograft rejection in a sublethally irradiated rat cardiac allograft model. Donors of reconstituting B lymphocytes were sensitized with three consecutive ACI skin grafts. Transplantation of a heart from an ACI strain donor into a Lewis strain recipient (complete RT1 mismatch) results in rejection in 6.8 +/- 0.3 days. When the allograft donor and recipient are irradiated with 650 cGy prior to transplantation, rejection occurs at 31.5 +/- 3.0 days. Irradiated recipients reconstituted with 10(6) syngeneic sensitized splenic B cells reject their grafts in 20.1 +/- 2.0 days, while reconstitution with 10(6) unsensitized syngeneic B cells has no effect on the rate of rejection (P = 0.0007). These data strongly suggest that sensitized B lymphocytes have a marked accelerating effect on the tempo of allograft rejection. PMID- 1881135 TI - Effect of controlled hemorrhage on tissue and serum cefazolin clearance. AB - Effects of blood loss on tissue and serum antibiotic levels were investigated in 30 New Zealand white rabbits. Studies were conducted over a 3.5-hr period after intravenous administration of cefazolin, 30 mg/kg, in control animals (Groups I and IV, n = 5 each) and animals having 50% (Groups II and V, n = 5 each) or 100% (Groups III and VI, n = 5 each) of their blood volume removed and replaced with either Ringer's solution (Groups I, II, and III) or rabbit whole blood (Groups IV, V, and VI) sufficient to maintain central venous pressures at baseline levels. Periodic samples of retroperitoneal fat, iliac artery, and serum were assayed for cefazolin concentration by disc diffusion. Decreased tissue antibiotic levels were observed in animals undergoing 100% blood replacement (Groups III and VI) compared to controls (Groups I and IV) in both fat (P less than or equal to 0.01) and artery (P less than or equal to 0.01) at 90 min. Decreased antibiotic serum half-life accompanying hemorrhage existed when comparing Group II to I (P less than or equal to 0.05), Group III to I (P less than or equal to 0.01), and Group IV to V (P less than or equal to 0.01). The increased antibiotic clearance related to blood loss in this study justifies reassessment of intraoperative dosing intervals. More frequent dosing may be required to maintain stable tissue and serum antibiotic levels during substantial operative hemorrhage. PMID- 1881136 TI - Age-related changes in the efficacy of crystalloid cardioplegia. AB - Recent work has shown that multi-dose St. Thomas' Hospital cardioplegia solution (STHC) may not provide reliable protection of the neonatal myocardium. We have used an isolated working heart model to study the age-related development of this observation. Sets of eight hearts from 2-, 4-, 6-, and 8-week-old rabbits were subjected to 90 min of ischemia at 10 degrees C. STHC was infused at 30-min intervals in a dose of 10 ml/kg. There were no differences in the preservation of ATP stores during ischemia among the groups. The percentage recovery of preischemic mean aortic pressure, left atrial pressure, and heart rate were not different among groups, but the percentage recovery of aortic flow (AF) (expressed as means +/- standard error of the mean) was significantly lower in the 2- and 4-week hearts (44.1 +/- 8.2 and 66.2 +/- 7.7%) than in the 6- and 8 week hearts (93.0 +/- 6.4 and 97.6 +/- 4.7%). We have confirmed that the use of multi-dose STHC impairs recovery of ventricular function in the neonatal rabbit heart. This effect, however, diminishes rapidly as the immature animal develops and is not present by 6 weeks of age. Additional experimentation is necessary to identify those aspects of the developing myocardium that account for these observations. PMID- 1881137 TI - Jejunal and ileal absorptive function after a model of canine jejunoileal autotransplantation. AB - The effects of intestinal transplantation on the physiologic functions of the gut are not well understood. Our aim was to determine the effect of a large animal model of small intestinal transplantation (disruption of all neural and lymphatic continuity) on selected absorptive functions of the jejunoileum. Seven dogs were studied before and at 1, 4, and 12 weeks after a model of jejunoileal autotransplantation, which avoids confounding factors of immune rejection, immunosuppression, and harvest ischemia. Jejunal function was assessed by quantitative [3H]-folate and D-xylose absorption and ileal function by quantitative 57Co-vitamin B12 absorption. The role of lymphatic continuity was assessed by fecal fat recovery following 5 days of a controlled, high fat diet (75 g/day). All dogs developed a profuse, watery diarrhea that persisted for 6 to 12 weeks and lost about 15% body weight; however, absorption of D-xylose, folate, and vitamin B12 was unaffected at any time point. Fat absorption postoperatively was only mildly abnormal (less than or equal to 8 g/day) at all time points in five of seven dogs despite complete lymphatic disruption. We concluded that jejunoileal autotransplantation does not markedly affect these specific jejunoileal absorptive functions. Fat absorption in most dogs surprisingly remains almost normal. Anatomic and physiologic consequences of intestinal transplantation do not appear to induce global abnormalities in all absorptive functions in the nonrejecting jejunoileum. PMID- 1881138 TI - Mechanism and prevention of ischemia-reperfusion-induced liver injury in rats. AB - This study was designed to clarify the mechanism of ischemia-reperfusion-induced rat liver injury and to evaluate the effect of long-acting superoxide dismutase (SOD-POE). Liver mitochondrial functional indices, i.e., the respiratory control index (RCI) and the rate of oxygen consumption in State III respiration (St. III O2), were decreased significantly to 1.33 +/- 0.06, mean +/- SD, and 54.4 +/- 3.7 natom/mg protein/min, respectively, after 120 min of ischemia, compared to respective preischemic values (3.94 +/- 0.21 and 80.2 +/- 3.9). These indices did not recover fully following 60 min of reperfusion (RCI, 3.25 +/- 0.17; St. III O2, 69.9 +/- 6.4). Tissue levels of adenosine triphosphate (ATP) were decreased to 2% of preischemic levels after 120 min of ischemia and remained at 39% of preischemic levels following 60 min of reperfusion. Increases in hypoxanthine and xanthine were observed after ischemia. SOD-POE improved the recovery of mitochondrial function (RCI, 3.70 +/- 0.20; St. III O2, 83.3 +/- 7.6) and also accelerated the recovery of ATP (53% of preischemic level). SOD-POE did not affect the decrease in ATP levels or the increase in purine nucleotide levels during ischemia. SOD-POE did not influence changes in tissue blood flow levels throughout the experiments. The leakage of adenine nucleotides immediately after reperfusion was observed (4.2 +/- 2.0 mumole/liter serum), and SOD-POE mitigated this leakage (1.3 +/- 0.5). Purine nucleotides are oxidizable substrates of xanthine oxidase, and an increase in superoxide radical generation by this enzyme might be expected in the ischemia-reperfusion process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881139 TI - Inert wound dressing is not desirable. AB - Four Yorkshire piglets were inflicted with a total of 92 split-thickness wounds 4.8 cm2 in area and 400 microns deep. The wounds were treated with eight dressing regimens under the same experimental design. The rate of reepithelialization of the wound was quantitated by a morphometric method. The magnitude of inflammatory reaction of the wound to the dressing was scored from histological slides. The results indicate a relationship between the rate of reepithelialization of split thickness wounds and the inflammatory response of the wound to the dressing. Dressings, such as collagen sponge, polyethyleneglycol, Duoderm, and lanolin ointment, induce moderate to severe inflammatory changes when placed on the wounds. These wounds reepithelialize significantly faster than control, gauze covered wounds. This contrasts with inert dressings, such as hydrated hydrogel membrane, Carbopol 934P, or Silvadene cream, which did not affect the rate of reepithelialization when compared with the healing of control wounds. Simultaneously, these dressings induced no or minimal inflammatory reaction in the wound tissue. Only when the inflammatory reaction to the wound dressing was excessive (methylcellulose) was the rate of reepithelialization of the wounds significantly inhibited in comparison with control wounds. We hypothesize that wound dressings, by inducing inflammatory reaction, enhance healing by activating cells, such as macrophages or fibroblasts, that produce growth factors and other mediators of the repair process. PMID- 1881140 TI - Liver bacterial clearance following hepatic artery ligation and portacaval shunt. AB - The reticuloendothelial system (RES) plays an important role in removing bacteria, endotoxins, and immune complexes from the circulation. Hepatic phagocytosis accounts for more than 80% of RES function. The dual hepatic blood supply (hepatic artery/portal vein) may be altered by pathologic states and surgical procedures. This study evaluates and compares the effect of hepatic artery ligation and portacaval shunt on hepatic trapping of viable Escherichia coli. Thirty rats were placed in three groups: Group I was composed of sham operated controls; Group II underwent end-to-side portacaval shunt (PCS); and in Group III, hepatic artery ligation (HAL) was performed. At 2 weeks following the operation 10(9) 35S-radiolabeled viable E. coli were injected via the tail vein. At 10 min, bacterial distribution in the different organs was determined. Tissue samples were processed for liquid scintillation counting. The final distribution of bacteria was calculated from the input specific activity (dpm/bacteria) and expressed as the mean percentage of injected viable E. coli per gram of tissue and per organ weight. There was a significant decrease of bacterial trapping by the liver in rats following PCS (Group II), 45.0 +/- 10.4% vs controls 77.1 +/- 3.73% (P less than 0.005). This was partially compensated for by a significant increase of bacterial trapping by the lung. The decreased clearance in PCS rats is due to a reduction in liver mass compared to that in controls. Bacterial localization in HAL (Group III) rats was similar to that in controls. These data show that PCS decreases hepatic clearance and increases pulmonary localization of viable E. coli. This phagocytic dysfunction may contribute to increased susceptibility to infection following portacaval shunt. PMID- 1881141 TI - Polymer-mediated electrostatic interactions between charged lipid assemblies and electrolyte solutions: a tentative model of the polyethylene glycol-induced cell fusion. AB - We developed a theoretical model to investigate the interaction between charged lipid aggregates and a water solution containing ions and uncharged polymers. The local concentration of ions and polymer chains around the lipid aggregate have been treated as variational parameters which can be found by minimizing the total energy of the system. We divided the energy into the following main contributions: (a) Solvation energy of the ions. This depends on the local polymer concentration through the variation of the solvent dielectric properties. (b) Ions-lipid aggregate interactions. These depend on the local concentrations both of the ion cloud and polymer chains. (c) Conformational energy of the polymer. This term is related to the inhomogeneous spatial density of the polymer segments. Any direct interaction between the charged lipid surface and the polymer coils has been intentionally neglected. The minimization procedure leads to a non-linear Poisson-Boltzmann equation coupled with a non-linear algebraic equation describing the polymer distribution. The solution of the above system allows one to calculate the ions and polymer spatial distribution around the lipid aggregate. The knowledge of such parameters is useful to predict the effect of non-ionic polymers on the structure and properties of lipid assemblies such as the mean area per lipid molecule, the aggregation number, the critical micellar concentration and the formation of immiscibility gaps in mixed lipid systems. A possible involvement of these parameters into the fusion process between lipid vesicles is discussed. PMID- 1881142 TI - A model of insulin distribution and uptake in the perfused rat liver. AB - Indicator dilution curves of 51Cr-EDTA and 125I-insulin injected into perfusate entering the rat liver in vivo are used as a basis for developing a mathematical model of insulin distribution and uptake within the organ. EDTA is not taken up by liver cells and therefore serves as a "volume marker" whose dilution curve reflects the characteristics of perfusate flow through the organ and through the cannulae. These two components are modelled separately but the same approach is used in each case, that is, the minimum number of delayed exponential terms sufficient to reproduce the dilution curves is determined and used as the basis for modelling. This allows the cannula, vascular and sinusoidal volumes to be identified and described as corresponding compartmental configurations. The shape of the insulin dilution curve is additionally influenced by binding to, and uptake by, liver cells. Binding of insulin to receptors on hepatocyte plasma membranes and subsequent internalization of the insulin-receptor complex is modelled by the introduction of additional compartments but this is found to be insufficient unless non-specific binding is also taken into account. The accuracy of determination of the rate constants for insulin-receptor dissociation and for endocytosis is improved by a sudden reduction in the pH of the perfusate about 100 sec after injection of the insulin bolus. This releases any residual receptor bound insulin and is modelled by a sudden shift in the insulin-receptor dissociation rate constant. Matching of the complete model to individual pairs of 51Cr-EDTA and 125I-insulin dilution curves allows vascular and sinusoidal volumes to be determined together with the binding and endocytic rate constants. Use of the model to investigate the effect of substances that modify these rate constants is briefly illustrated in the case where the liver is preperfused with 5 mM indomethacin. The model can also be used to simulate the internal distribution and uptake of insulin with any nominated input function and any set of parameters; this is illustrated by comparing the impulse response in the normal case and that in which indomethacin has been preperfused. Although the present study is confined to insulin, the model and methodology that is developed should be applicable to other ligands for which the hepatocyte carries specific receptors. PMID- 1881143 TI - A superior theory? PMID- 1881144 TI - The ordering of nucleotides in the DNA: strong pyrimidine-purine patterns near homooligomer tracts. AB - Here, we study the frequencies of occurrence of homooligomers flanked by one base, XnU or UXn, where X = A, C, G, T and U not equal to X. Specifically, we search for preferences (or discriminations) in their nearest neighbor doublet, VV. Extensive analysis of the data base reveals striking patterns in such VVUXn or UXn VV oligomers (V = A, C, G, T). With very few exceptions, if the VV and Xn are composed of complementary nucleotides, those oligomers having a pyrimidine (Y)-purine (R) junction are preferred over those with an RY one. If the VV and Xn nucleotides are not complementary, the RY junction oligomers are preferred over their YR counterparts. These trends are observed consistently in eukaryotic and prokaryotic sequences. They are particularly striking in the YR greater than RY oligomers containing complementary nucleotides. The general preferences and discriminations described here are in the same direction as our previous results for homooligomer tracts. These recurrences, along with some additional universal "rules", aid in our understanding of the ordering of nucleotides in the DNA. PMID- 1881145 TI - On the frequencies of nucleotides and nucleotide substitutions in conservative regulatory DNA sequences. AB - We present data on the frequencies of nucleotides and nucleotide substitutions in conservative DNA regions involved in the regulation of gene expression. Data on prokaryotes and eukaryotes are considered separately. In both cases DNA strands complementary to those which serve as templates for RNA-polymerase have low frequencies of cytosine. The most conservative positions also have an increased frequency of adenine. Various substitutions in the series of homologous regulatory DNA sequences, as compared to their consensuses, have different frequencies. In prokaryotes guanine in a consensus sequence is substituted for at the lowest and adenine at the highest frequency, whereas in eukaryotes cytosine is substituted for at the lowest and guanine at the highest frequency. In both cases the nucleotides substituted for are most frequently replaced with cytosine. Deviations from consensus sequences tend to cluster in adjacent positions. The more pronounced the consequences of a nucleotide substitution are the higher is the frequency of substitutions in adjacent positions. Possible explanations for these phenomena are discussed. PMID- 1881146 TI - The quantitative investigation of the binding process of calcium blocking drugs in a sinoatrial node. AB - Application of existing models of sinoatrial node pacemaker activity and of channel-drug interaction allow us to reproduce action potential changes as a result of the blocking effect of drugs. Two calcium antagonistic drugs, nifedipine and mesudipine, were investigated and as a result averaged rate constants of binding and unbinding were evaluated. The procedure applied which is based on experimental results and on computer simulations, can be used as an initial step for comparison of different drugs. PMID- 1881147 TI - Distinguishing mechanisms for the evolution of co-operation. AB - The existence of co-operation between species has been cast as a problem to the selfish-gene view of evolution: why does co-operation persist, when it would seem that individual selection should favor the unco-operative individual who exploits the co-operative tendencies of its partner and gives nothing in return? The recent literature has emphasized one type of model as underlying the evolution and stability of interspecific co-operation, which we term the "partner-fidelity" model, and which is typified by the game theory model known as the iterated Prisoner's Dilemma game. Under this mechanism, individuals are associated with the same partner(s) during an indefinite sequence of interactions. Individuals who at any time fail to co-operate with their partner can be penalized by those same partners in subsequent trials, hence the co-operation can be evolutionarily stable. Many examples of biological co-operation that have been offered appear to conform to this model. However, a few examples appear instead to fit a different and unrecognized mechanism, termed "partner-choice". Under partner-choice, individuals are associated for just one interaction, but an asymmetry enables one member to differentially reward co-operative vs. unco-operative partners in advance of any possible exploitation. Possible examples of co-operation maintained through partner-choice mechanisms are provided by the yucca/yucca moth system and the fig/fig wasp system. PMID- 1881148 TI - Evolution of the sterile caste. AB - Biased sex ratios are expected to affect the conditions of the evolution of worker behaviour in malehaploid populations. In a subsocial, malehaploid species an association to female-biased brood sex ratios favours the evolution of worker behaviour. There are various reasons to expect such an association. The critical worker efficiency threshold required for worker behaviour to evolve is lower when looked at from the viewpoint of the mother than from that of the daughter. In this mother-daughter conflict, the mother can expect some help from her other offspring to resolve the conflict in her favour. In semisocial species the sex ratio biases have a less significant role and the worker behaviour can evolve more easily in malehaploid than in diploid populations. Furthermore, limited dispersal (due to the risks attached to it) is expected to favour worker behaviour in malehaploid but inbreeding in diploid populations. In addition to the genetic mechanisms that determine the critical worker efficiency threshold, it is essential to pay attention to those ecological factors that affect the actual worker efficiency in nature. Several such factors exist but it is not easy to associate them with the common occurrence of eusocial species in the Hymenoptera. PMID- 1881149 TI - How far can one go in the field of structural elucidation of natural products? AB - Structural elucidation of bioactive compounds has always been and remains a field of interest for organic chemists. Tools have constantly evolved over the past fifty years and the field has become so sophisticated and relies so heavily on instruments and computers that is becoming an area for specialists. Specialization has become such that the natural product chemist now faces X-ray professionals, mass spectrometry specialists, not to speak of NMR experts; all these people use different tools, different quantities of material and it may happen that once our natural product chemists opens the door of one of their laboratories, he is not welcome in the others anymore. The purpose of this paper is to discuss briefly what can be done best with each of the tools. It will be also shown that chemistry may still find a use, especially when problems are very difficult to tackle. Examples will be chosen among terpenes, antibiotics and toxins. PMID- 1881150 TI - Digitalis: is there a future for this classical ethnopharmacological remedy? AB - Withering's (1741-1799) greatest merit is not so much that of having discovered the therapeutic value of foxglove in hydropsy, since this indication (among others) was already part of traditional medicine, but actually during a decade of carefully recording clinical observations, he authoritatively settled definite guidelines for its use. In spite of its further utilization in many additional illnesses such as madness, foxglove, and later its main heteroside digitoxine, progressively reached their eventual place in the treatment of supraventricular arrhythmias and in congestive heart failure. In the latter indication, however, its value is now being questioned; it is being accused of augmenting myocardial work due to its vasoconstrictor properties, of favoring dysrhythmic events in a disease already burdened with a 50% arrhythmia mortality, and actually of having a low therapeutic index. Even though being discarded by a number of cardiologists, digitoxine still remains in the appraisal of others as an indispensable medicine. PMID- 1881151 TI - Can ethnopharmacology contribute to the development of new anticancer drugs? AB - Ethnopharmacologic and ethnomedical information has been poorly utilized in the past in the search for new and effective treatments for cancer. In spite of this, plants have been a very viable source of clinically useful compounds, leads for synthetic modification and tools for mechanistic studies. In this paper, a new strategy for the discovery of anticancer agents from plants is proposed in which ethnomedical information is correlated against pertinent published chemical and biological information, resulting in a prioritization of plants for collection. Authenticated plants are extracted and the extracts tested in a broad array of more than 20 human cancer cell and mechanism-based assays through a cooperative research program involving a university, a research institute and a pharmaceutical company. Bioactivity-directed fractionation will be carried out at all three sites, with a view to identifying novel compounds which will serve as candidates for preclinical testing. PMID- 1881152 TI - Ethnopharmacology and the development of natural PAF antagonists as therapeutic agents. AB - Ginkgolides are unique twenty-carbon terpenes, occurring naturally only in the roots and leaves of Ginkgo biloba. The molecules incorporate a tert-butyl group and six 5-membered rings, and are specific and potent antagonists of platelet activating factor (PAF), a potent inflammatory autacoid. Studies in animal models with the most potent ginkgolide, BN 52021, and other specific PAF antagonists have demonstrated that PAF plays an important role in pathologies such as asthma, shock, ischemia, anaphylaxis, graft rejection, renal disease, CNS disorders and numerous inflammatory conditions. Ginkgolides are now being developed as therapeutic agents and very promising results have been obtained in clinical trials on shock, organ preservation and thermal injury. In addition to ginkgolides, several other types of natural PAF antagonists have been identified from various medicinal plants. These compounds have not only helped to explain the pharmacological basis of several traditional medicines, but have also provided man with a valuable new class of therapeutic agents. PMID- 1881153 TI - Can ethnopharmacology contribute to the development of antimalarial agents? AB - The resistance of Plasmodium falciparum, the cause of tertian malaria, to synthetic antimalarials, together with the resistance of the vector mosquitoes to insecticides, has resulted in a resurgence in the use of quinine and a search for new antimalarial agents. In recent years, artemisinin, isolated from Artemisia annua which is used in Chinese traditional medicine for the treatment of malaria, has proved to be effective in the treatment of cerebral malaria due to chloroquine-resistant strains of P. falciparum. The development of in vitro tests utilising P. falciparum obtained from malaria patients means that it is possible to use bioassay guided fractionation of active extracts in order to isolate active principles. A number of laboratories throughout the world are currently investigating plants used in traditional medicine for their active constituents. Some of their results will be described and in particular two aspects of our investigations with species of Simaroubaceae and Menispermaceae will be discussed. There is every possibility that such approaches which use leads from Ethnopharmacology will result in the development of new antimalarial agents. It is vitally important to those populations relying on traditional medicines for the treatment of malaria that the safety and efficacy of such medicines be established, their active principles determined and that reproducible dosage forms be prepared and made available for use. PMID- 1881154 TI - Can ethnopharmacology contribute to the development of anti-fertility drugs? AB - China, one of the developing countries with approx. one-fifth of the world population, has been making great efforts in controlling her population size. One of the efforts being stressed is to look into the practicability of employing Chinese herbal medicine for fertility control. The rich ethnopharmacological descriptions in the ancient books of herbal remedy and those scattered in the folklore medicine contribute the possibility of this approach. After a discussion concerning the facets of antifertility drugs linked with male or female fertility regulation, several selected examples are presented, which include yuehchukene (isolated from Murraya paniculata), pseudolarix acids A and B (from Pseudolarix kaempferi), mardekoside A (from Mardenia koi), gardenic acid and gardenodic acid A (from Gardenia jasminoides) as early pregnancy terminating agent, for fertility regulation in females; whereas gossypol (from cottonseed oil) and total glycosides of Tripterygium wilfordii (GTW) as antispermatogenic agent for fertility regulation in males. Further research and development strategies of antifertility drugs from herbal medicines have also been discussed based on a collective research data in this field worldwide. PMID- 1881155 TI - Does pharmacology corroborate the nicotine therapy and practices of South American shamanism? AB - The use of tobacco by South American Indians is deeply rooted in their culture and thought. From early pre-Columbian times to the present, tobacco has functioned as an important psychotropic drug for magico-religious, medicinal and recreational purposes. Native interest in tobacco centers on the nicotine alkaloid it contains. Data culled from about 1800 sources and pertaining to nearly 300 societies reveal that South American Indians employ six major and several minor means of nicotine application. There exists a close functional relationship between tobacco and shamanism. The empirical ethnographical data base of nicotine application is compared to the comprehensive literature of experimental clinical studies of tobacco and nicotine. Ritual tobacco use aims to achieve acute nicotine intoxication. The pharmacological effects of the alkaloid on the human body are shown to have informed shamanic therapeutic practices and beliefs. Closely associated with soil cultivation, tobacco use in the New World is much more recent than shamanism. Thus, it is not the drug that gave origin to shamanic religion but religion that informed the effects of the drug. PMID- 1881156 TI - What are the possibilities and limits of therapy with European native drugs in modern clinical medicine? AB - Concerning therapy with European native drugs in modern clinical medicine, a clear distinction has to be made between its possibilities and limits on a scientific basis and its possibilities and limits according to the present position of phytotherapy in the different countries of the European Community. On a scientific basis phytopharmaceuticals are used for therapy in a variety of diseases in the clinic as well as in medical practice. The clinical use of phytopharmaceuticals is limited by the kind of acute and severe diseases predominantly treated in the hospital. These diseases require immediate measures with strong acting pharmaceuticals. In the practice of the general practitioner indications for phytopharmaceuticals in principle are the same as in the hospital. The relatively more frequent use of phytopharmaceuticals by the practitioner is related to the fact that he is mainly concerned with mild health disturbances and diseases and chronic sufferings which are destined for treatment with herbal medicines. PMID- 1881157 TI - How and why should we standardize phytopharmaceutical drugs for clinical validation? AB - Standardized extracts are needed to carry out reliable clinical trials. The standardization of an extract does not include only a whole of analytical controls: it requires also a thorough description of the starting drug and of the whole extraction process, both basic items for the constancy of the quality of an extract. Another not minor aspect in the standardization of an extract is its nomenclature which must include all the necessary data for a clear definition (drug, physical state, solvent of extraction, composition) of the extract itself. Two examples of standardization are described, one concerning an extract whose therapeutical active constituents are known (anthocyanoside complex of Vaccinium myrtillus) and the other concerning an extract whose constituents must be regarded as chemical markers (Pygeum africamum extract). PMID- 1881158 TI - The pharmacology of psychoactive alkaloids from ephedra and catha. AB - Ever since the introduction of the alkaloid ephedrine as an anti-asthmatic, the CNS stimulatory effects of this sympathomimetic have been a problem in therapy. Indeed, the use of ephedrine is not only limited by its cardiovascular effects, but also by the occurrence of insomnia, restlessness and anxiety. Exceptionally, ephedrine may even induce toxic psychosis, and the possibility of this side effect has recently received renewed attention. Besides ephedrine, the ephedra plant contains some norpseudoephedrine. This substance is also called cathine, because it is a major alkaloid of Catha edulis or khat, a plant that is widely used as a stimulant in certain countries of East Africa and of the Arab Peninsula. The effects of khat have been explained formerly by those of cathine; some time ago, however, the labile alkaloid cathinone was discovered in khat. This substance is the keto-analog of cathine; it is therefore more lipophilic and penetrates easily to its sites of action in the central nervous system. Indeed, cathinone has been found to be a highly potent CNS stimulant and it is now known to be the main psychoactive constituent of khat; the results of various in vitro and in vivo studies indicate that cathinone must be considered a natural amphetamine. In confirmation of this view, it has recently been demonstrated that cathinone has in humans marked euphorigenic and psychostimulant effects. As the case may be, these findings may lead, together with epidemiological data, to a reconsideration of the use of khat as a stimulant and social drug. PMID- 1881159 TI - What is ethnobotany today? AB - A review is given of contemporary ethnobotany. Emphasis is placed on the interdisciplinary nature of the subject and most progress is made when botanists, anthropologists, ecologists, chemists, etc. work in close collaboration. Ethnoecology, the study of the management systems of indigenous peoples, is particularly important for its application to the creation of sustainable use systems in the tropics. This must include the study of peasant agriculturalists who have adapted many techniques from cultures that have long been extinct. Quantitative studies of the extent to which rainforest Indians use the forest have provided many data useful for conservation. The study of indigenous medicines is leading to the discovery of new medicines and agrochemicals. When commercial benefit is gained from products derived from information obtained from indigenous peoples, it is essential to ensure that they and their countries benefit from the royalties. There is a great urgency for further ethnobotanical research before indigenous cultures and natural habitats are destroyed. PMID- 1881160 TI - Is there an industrial future for phytopharmaceutical drugs? An outline of UNIDO programmes in the sector. AB - Although a substantial proportion of the health-care expenditure of developing countries is spent on the acquisition of drugs, this is only sufficient to serve about a quarter of their population. Therefore it is inconceivable that WHO's goal of HEALTH FOR ALL by the year 2000 could even be approached without consideration being given to the role in health care systems of herbal medicines. In this endeavour, traditional herbal medicines must perforce be granted the benefits of modern science and technology to serve future global needs. Here we are addressing both a contigency situation as well as a long term one. In developing nations there is a dire need for an improved supply of therapeutic agents for a variety of diseases that are characteristic of deprivation and poverty. In addition herbal medicines promise to provide both concepts of therapy, as well as therapeutic agents in areas where modern medicine has few answers. UNIDO's programmes for technical assistance to developing nations aim at the fullest utilisation of traditional herbal-based pharmacopoeias in addressing both these situations. They have employed a multi-disciplinary approach to the industrial production of herbal medicines. The projects endeavour to utilise the natural flora, judiciously, for selection, domestication and crop-wise cultivation of medicinal plant species for industrial processing. National R & D efforts have been strengthened to include the development of expertise in several areas such as instrumental analyses, biological assessment of raw materials as well as products. Process technology development has received special attention. A versatile poly-functional pilot plant has been developed to enable the production of herbal preparations as well as extracts and phytochemicals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881161 TI - Legal requirements for the use of phytopharmaceutical drugs in the Federal Republic of Germany. AB - The legal status for herbal remedies is defined by the Drug Law of 24 August 1976 in the version of the forth law amending of April 1990. For finished drugs a marketing authorization is obligatory. Herbal finished drugs hae to comply with the same criteria for quality, safety and efficacy as all other finished drugs. Marketing of finished herbal drugs is possible by three ways: 1. Procedure of evaluation and validation of old medicines. Finished drugs registered in 1978 did possess a provisional marketing authorization and could be on the market until the end of April 1990. The medical evaluation of these drugs is mainly based on bibliographic data and it is done by a special expert committee, the Commission E. It is documented by a monograph which is the basis for the assessment of these drugs starting this year. 2. Standardized marketing authorization. Medicines which do not represent a direct or indirect risk for health can be exempted from the need of an individual marketing authorization by monographs of standardized marketing authorizations. If a applicant refers to such a monograph he does not have to present any documentation. 3. Individual applications for marketing authorization. In this procedure a complete documentation including the results of analytical tests, results of the pharmacological and toxicological tests and results of clinical or other medical tests are required. Drugs sold outside pharmacies and referring only to traditional uses without clinical evidence for efficacy have to be labelled as "traditionally used". PMID- 1881162 TI - What are the legal requirements for the use of phytopharmaceutical drugs in France? PMID- 1881163 TI - Sociopolitical, economical and ethical issues in medicinal plant research. AB - Medicinal plant research may be pursued with several goals: the understanding of a native medical system, the elucidation of the rational basis for the medicinal use of a certain plant species, the development of low cost phytotherapeutics, the discovery of prototypic drugs, and so on. More often than not, the research project starts with the collection of indigenous medical knowledge in various parts of the world and generates a dissertation, a scientific paper or a drug. Usually, indigenous knowledge was crucial to the development of such products; nevertheless, indigenous groups tend not to benefit from the achievements of research. Ethnopharmacology involves a series of sociopolitical, economic and ethical dilemmas, at various levels. Most research projects involve more than one country (e.g., field work in a remote part of an underdeveloped country). Frequently host country scientists, visiting scientists, and informants disagree about these dilemmas. As a result, such research efforts are perceived as scientific imperialism; scientists are accused of stealing plant materials and appropriating traditional plant knowledge for financial profit and/or professional advancement. Many governments, as well as indigenous societies are increasingly reluctant to permit such research. Increasingly, funding for field work utilizing indigenous informants is coming from industry. Historically neither native populations nor host countries have shared to a significant extent the financial benefits from any drug that reaches the market. Unless these issues are amply discussed and fairy resolved, medicinal plant research runs the risk of serving ethically questionable purposes. PMID- 1881164 TI - Should we set a place for diet in ethnopharmacology? AB - Ethnopharmacologic inquiry is most invincibly pursued by addressing "medicinals" across the divers contexts through which populations gain exposure to the material of their pharmacopoeia. Attention to multiple categories of use advances our comprehension of indigenous health care by providing a framework for laboratory investigations that explore the bioactive potential of the materia medica to influence the occurrence and expression of disease, and that determine how those physiologic outcomes may be further mediated by the context-specific vicissitudes of preparation, combination and consumption. Consideration of the dietary contexts of local "medicines" is central to this wider perspective. PMID- 1881165 TI - Interest and limitation of a global ethnopharmacological survey. AB - Since 1983 an ethnopharmacological research called the TRAMIL Programme (Applied Research on the Traditional Popular Medicine in the Caribbean Basin) has been underway in several countries of the West Indies and Central America. The programme, which started in Haiti and in the Dominican Republic, has now extended to Colombia, Costa Rica, Dominica, Guatemala, Honduras and Venezuela. The most important goal of the programme is to evaluate the traditional use of medicinal herbs in order to help unprivileged populations from this geographical area. The study is approached from the point of view of solutions to everyday health problems, rather than as a simple catalogue of plant or traditional remedy usage. An appropriate methodology is employed, including inventory and botanical determination, bibliographical research, study of the unknown species through analytical, toxicological and/or pharmacological methods and transmission of controlled information which ensures the value of natural medication to the public. The TRAMIL Programme leads to protection of cultural heritage and integration of effective and secure traditional remedies in primary health care. PMID- 1881166 TI - Is there any danger in using traditional remedies? AB - The question, whether the use of traditional drugs can entail a health risk, is a rhetorical one. It is well-established that all sorts of vegetable, animal and mineral remedies used in a traditional setting are capable of producing serious adverse reactions. In fact, the medical and toxicological literature is so replete with examples that any attempt to cover them in just thirty minutes would be futile. Instead, the lecture will be largely devoted to a general outlook that may help to put ethnotoxicological case reports and research data in a realistic perspective. The principle that the expected benefit of a drug must outweigh its potential risk applies as much to traditional products as it does to synthetic drug preparations. No patient deserves to be treated with a remedy that is worse than the disease. It is essential, however, that traditional drug therapies are submitted to an appropriate benefit/risk analysis. With respect to the expected benefit, not only pharmacological efficacy should be appraised, but also the social utility of the drug in its cultural context. With regard to potential risk, it is of vital importance to account for confounding factors, such as intuitive risk perception. To assure that ethnotoxicological research efforts have an optimal impact on public health care, practically relevant results must be disseminated in a manner respectful of traditional medicine. PMID- 1881167 TI - Native drugs of Vietnam: which traditional and scientific approaches? AB - For thousands of years, our people treated diseases with herbs and plants which were gathered from gardens and forests. The recorded medical literature which now remains dates only after 10th century. In the history of Vietnamese national medicine, two names in particular stand out before 18th century. The first one is Tue Tinh of the 17th century, author of two treatises: Nam Duoc Than Hieu (The Miraculous Efficacy of Vietnamese Medicines) describing 580 indigenous drugs in 3873 prescriptions for 10 clinical specialities and Hong Nghia Giac Tu Thu. (Medical book from village Hong Nghia) summarizing the indications of 630 drugs with a theoretical part of traditional medicine. The second name would be Le Huu Trac (1720-1791) writing as Hai Thuong Lan Ong, author of the great treatise of traditional medicine with more than 30 volumes. From generation to generation by oral tradition and through literature, people have collected a lot of medicinal plants and especially a lot of medicinal prescriptions based on a long empirical knowledge of medicinal and toxic plants. After the August Revolution (1945), traditional medicine in our country was rehabilitated to its state position. Prof. Dr. Do Tat Loi, one of the authors of this paper, was busy over 40 years compiling the medicinal plants, animal and mineral origins into a book (more than 1200 pages): Medicinal Plants and Drugs from Vietnam. A general part, the theoretical bases of eastern medicine, basic principles of drug identification, processing and preparation, study of drug efficaciousness and particular guides for using traditional drugs are presented. In the second part, the author introduces more than 700 drugs common in Vietnam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881168 TI - Selection of traditional medicines for study. PMID- 1881169 TI - Historical perspective and future of ethnopharmacology. PMID- 1881170 TI - One man's poison, another man's medicine? AB - Poisonous plants and animals are widespread in nature and have been used for a great variety of purposes. Brief discussions of a number of examples: aconite, ergot, Euphorbiaceae/Thymelaeaceae, curare, cardiac glycosides, triterpenoid saponins and animal toxins, make the point that, in addition to allowing their use as medicinal agents, the study of such substances has opened up new areas of (bio)chemistry, physiology and pharmacology. But even though the compounds concerned have a relatively low molecular weight, in some cases their examination had to wait until appropriate methods of investigation became available. Understanding the modes of action has allowed the molecules to be used as starting points for the development of useful medicinal agents, a better appreciation of structure-activity relationships having led to improvements in the properties desired. With the advent of methods for the investigation of high molecular-weight proteins, polypeptides, polyketides, etc., it is now possible to enter entirely new fields and to study more complex materials derived from plant, animal and other sources. It is here that future developments, coupled with the possibility of more specific targeting, hold most promise for the beneficial utilization of otherwise highly poisonous substances. PMID- 1881171 TI - Looking for new drugs: what criteria? AB - How to look for new drugs? What guidelines to use? Have we to continue investigations on plant and marine organisms? These questions arise frequently today. A pharmacological effect results from the addition of many effects at a molecular level, i.e. the interaction between a ligand and a receptor. As long as the chemical structure of this receptor remains unknown, studies of Nature's resources will yield the largest reservoir of new drugs. Nature provides our imagination with the pattern of novel biologically active molecules. Criteria classically used in the past to select plants for study were chemotaxonomy, ethnopharmacology or pharmacotaxonomy. Examples will be taken from personal experience, to illustrate work done according to the chemotaxonomical approach (Ochrosia and ellipticines), and the ethnopharmacological approach (antiinflammatory properties of Euphorbiaceae from New Caledonia). Taking into account that one of the major problems we have to face is the unsatisfactory classical pharmacological testing procedure, we have tried to set up a network grouping biologists and chemists. Among many results obtained, one concerns the use of the mammalian hypothalamo-pituitary system to screen effects of alkaloids extracted from Psychotria oleoides, a Rubiaceae collected in New Caledonia. Psycholeine exhibits an intriguing activity on GH release. Another result concerns the influence of a Labiatae extract on the adenylate cyclase system: 9 HODE extracted from Glechoma hederacea stimulates the basal level of enzyme activity in platelets, this activity being possibly involved in the folk uses claimed. Using the tubulin test to screen antimitotic activities of plant extracts, the biological activity of rhazinilam has been demonstrated as responsible for the antitubulin activity of a Malaysian plant, Kopsia singapurensis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881172 TI - Natural products as probes for new drug target identification. AB - One traditional aspect of natural products in medical research has been their use in the identification and investigation of the physiological/pathological role of receptors and enzymes as possible targets for drug design programmes. Classical examples of this function of natural products in drug research can be seen in the investigation of the cholinergic system. For example, the importance of alkaloids such as nicotine, physostigmine and curare for research into the nicotine receptor and muscarine, pilocarpine and the tropane alkaloids on the muscarinic receptor. On binding of a ligand to its cell surface membrane receptor and prior to a physiological/pharmacological response two mechanisms are currently known to be involved in membrane signal transductance. In the minority of cases signal transductance involves the direct opening of an ion channel, for example sodium ion influx, but in the majority of cases involves stimulation of a family of G proteins and subsequent activation of second messenger systems. For example, the cyclic-AMP/adenylate cyclase system and the phosphoinositol cycle. In this communication, the part played currently by the tumour-promoting and pro inflammatory phorbol esters from the plant family Euphorbiaceae in furthering our understanding of the role of a group of related kinases from one arm of the phosphoinositol cycle as a signal transduction pathway will be illustrated. The possibilities of using these new receptors as targets for future drug development will also be described. PMID- 1881173 TI - The evolution of single lung transplantation for emphysema. The Washington University Lung Transplant Group. AB - Classic transplantation dogma mandated bilateral lung replacement for lung transplant candidates with end-stage emphysema to avoid air trapping in the native lung and subsequent crowding of the newly transplanted lung. During a recent 12-month period 11 patients with emphysema received a single lung transplant. There was no hospital mortality and only one patient had any notable degree of air trapping in the native lung. Substantial improvement in pulmonary function was seen as early as 2 weeks after transplantation, with significant functional improvement seen by 6 weeks, despite some residual ventilation perfusion mismatch. We have demonstrated the utility and safety of single lung transplantation for patients with end-stage emphysema, and it is our operation of choice in recipients more than 50 years of age. PMID- 1881174 TI - Sternal wound infections and use of internal mammary artery grafts. AB - Previous studies have provided conflicting evidence as to whether an increased risk of mediastinitis is associated with use of the internal mammary artery as a coronary bypass graft. In this study the effects of internal mammary artery grafts on wound complications were analyzed in a prospective, nonrandomized fashion. At New York University Medical Center from January 1985 through May 1988, 2356 patients underwent isolated coronary revascularization. Among these patients 1394 received one or more internal mammary artery grafts (group I) and 962 had vein grafts only (group II). Group I had a mean age of 59.5 years versus 67.7 years in group II; diabetes was equally present in both groups (22.7% versus 24.7%). Operative mortality rate was 1.3% in group I and 5.6% in group II. Sternal infection was significantly more prevalent in group I (2.2%, 31/1394) than in group II (0.8%, 8/962). Multivariate analysis revealed that aortic crossclamp time, use of a single internal mammary artery graft, use of a double mammary graft, and diabetes were associated with increased risk of sternal infection. The use of bilateral internal mammary artery grafting doubled the odds ratio of the risk compared with use of a single mammary graft, and the combination of diabetes and double internal mammary artery grafts increased the odds ratio 13.9-fold. Patients with an internal mammary artery graft who had sternal infection had a longer period of hospitalization than patients without a mammary artery graft who had sternal infection. We conclude that the risk of sternal infection is increased by the use of an internal mammary artery graft, especially use of double mammary grafts in the presence of diabetes. PMID- 1881175 TI - The influence of preoperative shock on outcome in sequential endocardial resection for ventricular tachycardia. AB - Sequential endocardial resection was used in 92 consecutive patients to treat ventricular tachycardia. All patients had coronary artery disease with previous myocardial infarction. All patients had repeated cycles of mapping and resection of arrhythmogenic foci in the normothermic beating heart until ventricular tachycardia was no longer inducible. Eighty-six patients (93%) survived to hospital discharge. The survival rate in patients normotensive at the time of operation was 98% and in patients in shock at the time of operation, 43%. By Cox regression analysis, preoperative shock was the significant predictor (p less than 0.001) of operative mortality. Seventy-four of the 86 operative survivors (86%) had no sustained ventricular tachycardia at initial postoperative electrophysiologic study when receiving no antiarrhythmic drugs. Eighty-three of the 86 operative survivors (97%) had no sustained ventricular tachycardia at final postoperative electrophysiologic study when using antiarrhythmic drugs as needed. After a median follow-up of 21 months (range 1 to 79 months) there were 4 sudden cardiac deaths, 12 other cardiac deaths, and 3 noncardiac deaths. There were no documented nonfatal episodes of sustained monomorphic ventricular tachycardia after hospital discharge. Use of the sequential endocardial resection technique is effective in curing ventricular tachycardia with low operative morbidity and mortality. PMID- 1881176 TI - Aortic dissection resulting from tear of transverse arch: is concomitant arch repair warranted? AB - Forty-seven patients with aortic dissection resulting from a primary tear located in the transverse aortic arch underwent surgical treatment. Twenty-six patients had acute type A, 7 had acute type B, 7 had chronic type A, and 7 had chronic type B aortic dissections. Of the 33 patients with acute dissections, 11 (7 acute type A and 4 acute type B) underwent concomitant arch repair with an operative (less than or equal to 30 days) mortality rate of 55% (35% to 73%, +/- 1 asymmetric 70% confidence limit) (2 of 7 acute type A and 4 of 4 acute type B). Concomitant arch repair was omitted in 22 patients with acute dissections (19 acute type A and 3 acute type B); the operative mortality rate was 41% (29% to 54%) (7 of 19 acute type A and 2 of 3 acute type B) (p = not significant versus arch repair). The overall survival rate for those with arch repair was 45% +/- 15% (+/- 1 standard error of the estimate) at 4 years, compared with 43% +/- 11% for patients without arch repair (p = not significant). Considering the type of dissection, the 4-year survival estimate for patients with acute type A dissections who underwent arch repair (5 hemiarch and 2 total arch) was 71% +/- 17% (versus 44% +/- 12% for acute type A patients without arch repair). There were no survivors among the 4 patients with acute type B dissections who had an arch repair (1 hemiarch and 3 total arch), whereas patients with acute type B dissections who did not undergo concomitant arch repair had a 4-year survival estimate of 33% +/- 27% (p = not significant versus arch repair). Four other patients with acute type B dissections resulting from an arch tear were managed medically and tended to have a slightly better prognosis (2-year survival estimate of 75% +/- 22% versus 14% +/- 13% for all surgically treated acute type B patients), but again this difference was not statistically significant. Multivariate analysis of the 47 surgical patients revealed that advanced age (p = 0.0008), preoperative dissection complications (p = 0.02), and other coexistent medical problems (p = 0.03) were the only significant, independent determinants of overall mortality. Initial arch repair was not a significant predictor. Nine percent (2/22) of patients with acute type A dissections who initially underwent isolated ascending aortic replacement required subsequent arch replacement; 1 died after reoperation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1881177 TI - Time course and extent of recovery of endothelium-dependent contractions and relaxations after direct arterial injury. AB - To determine the time course of the return of endothelium-dependent relaxations and contractions during intimal regeneration, we performed balloon endothelial denudation of the thoracic and abdominal aorta of male Lewis rats and examined smooth muscle function and endothelium-dependent responses in vitro at 1, 2, 4, and 8 weeks after aortic injury. At each study interval during endothelial cell regeneration, vascular smooth muscle contracted and relaxed normally to direct stimulation with norepinephrine and sodium nitroprusside. Endothelium-dependent contractions to serotonin returned to normal at 1 week and developed into a hypercontractile response at 8 weeks. Endothelium-dependent relaxations to acetylcholine returned to normal at 8 weeks, but endothelium-dependent relaxations to adenosine diphosphate remained impaired. These experiments demonstrate that regenerating endothelium regains the ability to produce contracting factor before relaxing factor, and it even exhibits potentiated contractile activity 8 weeks after injury. Thus, after direct arterial injury, regenerating endothelium has abnormal endothelium-dependent function that predisposes the vessel to vasospasm and thrombosis. PMID- 1881178 TI - Pediatric heart transplantation after operations involving the pulmonary arteries. AB - A prohibitive perioperative mortality has been previously ascribed to pediatric heart transplantation after palliative operations for congenital heart disease involving the pulmonary arteries. Of 46 children who have undergone heart transplantation at our institution between June 1984 and February 1990, 7 (15%; mean age 8 +/- 3 years; range 1 to 18 years) have previously undergone such operations: right ventricle to pulmonary artery conduit/homograft for levo transposition of the great arteries (2), Waterston shunt for tricuspid and pulmonary atresia (1), pulmonary artery banding for single ventricle (1), Fontan procedure for single ventricle (1), first-stage Norwood procedure for hypoplastic left heart syndrome (1), and classic right Blalock-Taussig shunt for atrioventricular canal with pulmonic stenosis (1). Three categories of pulmonary artery anatomy that require different approaches to reconstruction at the time of transplantation are recognized: abnormalities of position, pulmonary outflow obstruction, and previous systemic- or atrial-pulmonary connections. At operation, individualized pulmonary arterial reconstruction was employed, including use of previously created right ventricular-pulmonary artery conduits/homografts and angioplasty (with and without pericardial patches). Transplantation was successful in all patients. Posttransplant right ventricular pulmonary artery pressure gradients and pulmonary vascular resistance indices were acceptable, with a tendency to decrease with time. Two patients had critical right ventricular failure postoperatively; one of them required support with extracorporeal membrane oxygenation. There was no perioperative mortality, with three deaths occurring from 5 to 39 months after transplantation. All surviving patients are in New York Heart Association functional class I. Techniques borrowed from the repair of congenital cardiac lesions can be applied to subgroups of children undergoing heart transplantation. Additional length of donor aorta and pulmonary artery should be harvested for possible use in designing pulmonary artery connections. Previous palliative operations involving the pulmonary arteries with associated complex pulmonary artery anatomy are not of themselves an insurmountable obstacle to successful heart transplantation. PMID- 1881179 TI - St. Thomas' Hospital cardioplegic solution. Beneficial effect of glucose and multidose reinfusions of cardioplegic solution. AB - The intention of this study was to determine whether glucose is beneficial in a cardioplegic solution when the end products of metabolism produced during the ischemic period are intermittently removed. The experimental model used was the isolated working rat heart, with a 3-hour hypothermic 10 degrees C cardioplegic arrest period. Cardioplegic solutions tested were the St. Thomas' Hospital No. 2 and a modified Krebs-Henseleit cardioplegic solution. Glucose (11 mmol/L) was beneficial when multidose cardioplegia was administered every 30 minutes. Including glucose in Krebs-Henseleit cardioplegic solution improved postischemic recovery of aortic output from 57.0% +/- 1.8% to 65.8% +/- 2.2%; p less than 0.025. The addition of glucose to St. Thomas' Hospital No. 2 cardioplegic solution improved aortic output from 74.6% +/- 1.9% to 87.4% +/- 1.9%; p less than 0.005. Furthermore, a dose-response curve showed that a glucose concentration of 20 mmol/L gave no better recovery than 0 mmol/L, and glucose in St. Thomas Hospital No. 2 cardioplegic solution was beneficial only in the range of 7 to 11 mmol/L. In addition, we showed that multidose cardioplegia was beneficial independent of glucose. Multidose St. Thomas' Hospital No. 2 cardioplegia, as opposed to single-dose cardioplegia, improved aortic output recovery from 57.4% +/- 5.2% to 74.6% +/- 1.9%; p less than 0.025, and with St. Thomas' Hospital No. 2 cardioplegic solution plus glucose (11 mmol/L) aortic output recovery improved from 65.9% +/- 2.9% to 87.4% +/- 1.9%; p less than 0.005. Hence, at least in this screening model, the St. Thomas' Hospital cardioplegic solution should contain glucose in the range of 7 mmol/L to 11 mmol/L, provided multidose cardioplegia is given. We cautiously suggest extrapolation to the human heart, on the basis of supporting clinical arguments that appear general enough to apply to both rat and human metabolisms. PMID- 1881180 TI - Diagnosis and management of purulent pericarditis. Experience with pericardiectomy. AB - Twelve cases of purulent pericarditis seen over 6 years are described. Staphylococcus aureus was the most common causative organism (six patients), and a respiratory infection was the most common preceding illness. The chest radiograph and echocardiogram were useful pointers to the diagnosis, but the electrocardiogram was not reliable. Antibiotics, surgical drainage, and pericardiectomy were used in all 12 cases. There was one death (8.3%), which occurred in a patient who was seen late. A review of the literature dealing with the diagnosis and management of this condition is presented. The importance of early diagnosis before a significant degree of cardiac tamponade occurs is noted. Although there is general agreement that surgical drainage is mandatory, the approach, methods of drainage, and extent of pericardial resection have been the subject of some discussion, and at least seven techniques are available. We conclude that pericardiectomy has a definite place in the management of purulent pericarditis. PMID- 1881181 TI - Experience in the surgical treatment of 331 patients with pulmonary hydatidosis. AB - Echinococcus disease is prevalent in Chile, with a rate of occurrence of 8.2 per 100,000. During a 15-year-period (1970 to 1985) we operated on 331 patients for pulmonary hydatidosis. Chest roentgenography was the main method of diagnosis. Among the total of 508 surgical procedures performed, pulmonary cystectomy was the most common (61.4%), whereas pulmonary resection was used in 31.4% of patients. The arc 5 test was used to confirm the diagnosis. Results were positive in 85% of the patients in whom it was done. There were 12.9% immediate postoperative complications in 12.9%, with late complications occurring in 4.10% and an overall mortality rate of 4.21%. These data suggest that hydatid cyst is still a common disease in our country, causing an important number of hospital admissions and a high percentage of complications. PMID- 1881182 TI - Glutaraldehyde-tanned mandril-grown grafts as venous substitutes. AB - The present study was performed to evaluate the potential of glutaraldehyde tanned mandril-grown grafts as caval substitutes. Short-term experiments consisted of 30 tubular grafts (35 x 8 mm), either of tanned collagen or polytetrafluoroethylene, that were sutured in the infrarenal inferior vena cava of pigs and removed 1 hour after implantation. There was no significant difference between the extent of the thrombus-lined graft surface in the biologic group and that in the polytetrafluoroethylene group. The amount of inner thrombus on tanned collagen grafts was significantly correlated to platelet activity. Long term experiments involved 30 similar segments of both materials, which were sutured in the inferior vena cava and harvested 7, 14, 28, 56, and 112 days after operation. The 112-day patency rate of collagen grafts was 67%. The 56-day patency rate of polytetrafluoroethylene grafts was 16%. The difference was statistically significant (p less than 0.01). Collagen grafts were lined by a thin neointima (200 micron) in all but two cases. The neointima was completely endothelialized within 4 weeks from implantation. In conclusion, tanned collagen grafts may represent a suitable material for venous replacement. PMID- 1881183 TI - Atherogenic effect of barotrauma on in situ saphenous veins in monkeys. AB - The objectives of this study were to determine whether veins subjected to barotrauma in situ undergo lipid uptake and morphologic changes to the same extent as veins grafted into the arterial circulation. Saphenous veins in seven stump-tailed macaque monkeys were exposed bilaterally and were circumferentially dissected free from surrounding tissue only at isolated sites. Segments of the veins were distended for 1 minute at hydrostatic pressures of 125 or 350 mm Hg. An undistended segment served as control. A cephalic vein graft was interposed in the femoral artery for comparison with in situ veins. The animals were fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. Saphenous veins and the cephalic vein grafts were explanted at 3 months for biochemical and histologic analyses. Cholesterol content in undistended saphenous veins was similar to that in veins distended at 125 or 350 mm Hg--105 +/- 15, 122 +/- 14, and 109 +/- 30 micrograms/100 mg wet tissue weight, respectively. Cholesterol content in cephalic vein grafts, 473 +/- 122 micrograms/100 mg, was greater (p less than 0.001) than in saphenous veins at all distention pressures studied. There was no difference among the distention pressures in the intimal fraction of saphenous vein wall, with the pooled value being 20% +/- 12%. This contrasted with the value of 59% +/- 11% in cephalic vein grafts (p less than 0.01). Endothelial coverage of the luminal surface in saphenous veins was similar among the levels of barotrauma, with the pooled value being 83% +/- 15%. Less of the lumen was covered with endothelium in cephalic vein grafts, 46% +/- 18% (p less than 0.01). Slightly more medial fibrosis was observed in cephalic vein grafts as compared with saphenous veins (p less than 0.05). These data demonstrate that barotrauma alone does not cause veins that remain in the venous system to undergo the lipid uptake or morphologic changes that occur in veins grafted into the arterial circulation in nonhuman primates. PMID- 1881184 TI - Spontaneous regression of isolated stenosis of the left main coronary artery. PMID- 1881185 TI - Successful coronary reimplantation for anomalous origin of the right coronary artery from the left sinus of Valsalva. PMID- 1881186 TI - Confidence intervals and survival estimates. PMID- 1881187 TI - Coronary artery compression at orthotopic cardiac transplantation. PMID- 1881188 TI - Tetralogy with small pulmonary arteries. PMID- 1881189 TI - Comments on: a new technique for one-stage radical eradication of long-standing chronic thoracic empyema. PMID- 1881190 TI - Left ventricular outflow tract obstruction after mitral valve repair assessed with intraoperative echocardiography: noninterventional treatment. PMID- 1881191 TI - Unilateral absent pulmonary artery: surgical repair with a new technique. PMID- 1881192 TI - Surgical management of native aortic valve endocarditis with aortic root abscess in a child. PMID- 1881193 TI - Chordal rupture as a late complication after mitral valve reconstruction. PMID- 1881194 TI - Mitral valve repair for anterior leaflet disruption after percutaneous mitral dilation. PMID- 1881195 TI - Selective fura-2 loading of presynaptic terminals and nerve cell processes by local perfusion in mammalian brain slice. AB - We describe a method for filling presynaptic terminals and cell dendrites in adult brain slices with the fluorescent calcium indicator fura-2 by localized perfusion of the acetoxymethyl (AM) ester derivative. The method provides labeling selectivity, similar to that produced by intracellular microinjection of fura-2, with the simplicity of bath application of membrane-permeant AM esters. Application of the method to mossy fiber tracts in hippocampal region CA3 and parallel fiber tracts in cerebellum resulted in distant presynaptic terminals well labelled with fura-2 without concomitant postsynaptic labelling, allowing optical measurements of calcium concentration in individual presynaptic terminals. Application of the method to CA1 pyramidal cells produced intracellular loading of apical dendrites with fura-2. Dendritic calcium changes produced by afferent fiber stimulation were similar to those determined from cells filled with fura-2 by intracellular microinjection. The method appears to be general, and should provide a means to fill projecting axons and dendritic processes in many areas of the brain with fluorescent indicators, allowing optical measurements of ion concentration dynamics to be performed in brain slice that were previously impractical. PMID- 1881196 TI - Computer-assisted three-dimensional reconstruction of the hippocampal region based on serial sections. AB - A large series of rabbit hippocampal Neo-Timm stained sections were manually aligned, digitized, and by a modified median filtration noise reduced and reconstructed into a three-dimensional object. From the presented simulated grey tone cuts of this object, the reader may assemble a rabbit hippocampal model, that spatially illustrates its anatomy. PMID- 1881197 TI - A modified "triangular pulse" stimulator for C-fibers stimulation. AB - A low-cost, battery-powered stimulator is described. This device generates asymmetric current pulse with fast rising phase and slower exponential decay. The current intensity and the time constant of the exponential decay can be independently and continuously varied. An example of using this stimulator to selectively activate C-fibers is demonstrated. In this case the total charge injected in one stimulation is only 67 nanocolumb, which is much smaller than that injected by conventional DC polarization technique. Detailed information about the circuit design is described. PMID- 1881198 TI - The pyrimido-pyrimidine derivative RA-642: a potent inhibitor of ferrous-induced lipid peroxidation in cell membranes. AB - The effects of three pyrimido-pyrimidine derivatives (RA-642, dipyridamole and mopidamol) on hydroxyl anion-induced lipid peroxidation in cell membranes from liver, brain, kidney, lung and heart rat tissue were studied using d-alpha tocopherol as standard for lipid peroxidation. Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation via the formation of hydroxyl anions. The products resulting from the reaction with thiobarbituric acid were taken to be indicators of lipid peroxidation. Thiobarbituric acid reactive substances (TBARS) were produced by different rat tissues in the following sequence: brain greater than liver greater than kidney greater than heart greater than lung. Dose-response and time-response curves were plotted for all compounds. Inhibiting concentrations, 50% (IC50), ranged from 0.3-1.4 microM for RA-642, and 2.5 and 4.6 microM for dipyridamole. In liver mitochondrial membranes, IC50s of these compounds were 0.4 +/- 0.2 and 5.8 +/- 1.2 microM, respectively. At 15 min after beginning TBARS production, dipyridamole and RA-642 did not exert any inhibitory effect. PMID- 1881199 TI - Study on the cerebral effects of sabeluzole. AB - The cerebral effects of subeluzole have been studied using the following methods: hypobaric hypoxia in mice, complete ischemia by decapitation in mice, anoxic hypoxia in mice, hemic hypoxia in rats, incomplete ischemia by bilateral carotid ligation in rats, anoxic hypoxia in rats and asphyxic hypoxia in cats. Sabeluzole was active in all the models used: it increased the survival time in hypobaric hypoxia (maximum at 40 mg/kg--by 92.0%, p less than 0.001), survival time in anoxic hypoxia in mice (maximum at 40 mg/kg--by 27.2%, p less than 0.001), gasping in decapitation model (maximum at 20 mg/kg--by 155.4%, p less than 0.001) and survival in hemic hypoxia (maximum at 2.5 mg/kg--by 21.1%, p less than 0.05). The duration of the effect as evaluated in the decapitation model was about 6 h. In incomplete ischemia in rats, however, it showed a weak effect. In anoxic hypoxia in rats, sabeluzole (5 mg/kg i.v.) increased the time latency between onset of anoxia and negative DC-shift by 20.5% and the K+e-threshold by 25.7%. In asphyxic hypoxia in cats, sabeluzole (0.5 mg/kg i.v.) counteracted the hypoxia induced decrease of the fast-wave amplitudes during the cortical resistance period and the hypoxia-induced decrease of the slow-wave and increase of the fast wave amplitudes during the cortical recovery period. PMID- 1881200 TI - Delayed lymphoid lung infiltration induced by cyclophosphamide in rats. AB - The pulmonary toxicity of antineoplastic drugs may be either direct or mediated by hypersensitivity. The aim of this study was to determine whether the mechanism by which cyclophosphamide (CY) damages the lung is direct and immediate or is the result of delayed immune toxicity. Pulmonary and immune changes following intraperitoneal injection of either CY (50 mg/kg) or NaCl (0.9%) in rats were assessed repeatedly over a period of 31 days by semi-quantitative histological studies, by measuring the pulmonary water/body weight ratio, dry lung weight/body weight ratio, heart weight and by assessing the transfer of [125I]-albumin in lung tissue. Lung damage was delayed and greatest at 11 (D11) and 14 (D14) days after CY injection. The pulmonary lesions were: (i) an infiltration of lymphocytes, plasma cells and histiocytes surrounding blood vessels and small airways, (ii) an alveolitis composed of macrophages, lymphocytes, a few neutrophils and a lymphoid infiltration of alveolar septa. Pulmonary water/body weight and dry lung weight/body weight ratios also increased and peaked at D11 D14 in CY-treated rats. No significant increase in [125I]-albumin in lung tissue or in heart weight was observed. It can be concluded that the mechanism by which CY induces a lymphoid lung infiltration is not direct and immediate but is the result of a delayed immune toxicity. PMID- 1881201 TI - Antagonism of caffeine-induced convulsions by ethanol and dizocilpine (MK-801) in mice. AB - Ethanol (1 and 2 g/kg, i.p.) and MK-801 (1 mg/kg, i.p.), N-methyl-D-aspartate (NMDA) receptor antagonist, offered protection against caffeine-induced convulsions in mice. Subeffective doses of ethanol (0.5-g/kg, i.p.) and MK-801 (0.5 mg/kg, i.p.) when administered concurrently, did not provide a facilitatory anticonvulsant action against caffeine-induced convulsions. Ethanol (0.5 g/kg, i.p.) when administered concurrently with adenosine (100 mg/kg, i.p.) or dipyridamole (5 mg/kg, i.p.) elicited a facilitatory anticonvulsant action. However, concurrent administration of subeffective doses of MK-801 (0.5 mg/kg i.p.) with adenosine (100 mg/kg, i.p.) did not offer a facilitatory anticonvulsant action against caffeine-induced convulsions. The protective effect of ethanol (1 g/kg, i.p.) against caffeine-induced convulsions was reversed by an imidazobenzodiazepine, Ro 15-4513 (4 mg/kg, i.p.). Ro 15-4513 did not produce any proconvulsant effect with caffeine. It is suggested that ethanol and MK-801 elicit their anticonvulsant actions against caffeine-induced convulsions through different receptor mechanisms and that the anticonvulsant action of ethanol may be partly attributed to its ability to act via central adenosinergic mechanisms. PMID- 1881203 TI - [The competition in health care must include collegial solidarity]. PMID- 1881202 TI - Indomethacin distribution in acute pharmacological response among rats. AB - A detailed examination of quantitative relationships of pharmacological action with plasma and tissue concentrations of indomethacin has been undertaken in the rat, after single oral administration of two sustained release preparations. In this study, drug was assayed by high performance liquid chromatography, whereas antiinflammatory response was assessed through the carrageenin-induced edema test. Significant linear correlations (p less than 0.001) were found between logarithmically transformed percent inhibition of edema and logarithmically transformed plasma, as well as tissue levels of indomethacin. However, the lack of significance for partial correlation regarding tissue concentration, contrary to plasma concentration, suggests that pharmacological response is more closely related to the latter, indicating that antidematous effect is mediated via the circulating drug rather than a local action in target tissues. This assumption is further discussed from the equivalence point of view. The relevance of this type of study in the case of topical administration of indomethacin is addressed as well. Taking into account the predictive value of the rat paw edema test for clinical efficacy, relationships similar to those observed are to be expected in man. The high correlation existing between plasma concentration of indomethacin and its pharmacological effect justifies the development and use of sustained release preparations in order to improve the outcome of treatment with this nonsteroidal antiinflammatory drug. PMID- 1881204 TI - [Inhumanity in a bureaucratic standard package?]. PMID- 1881205 TI - [Physicians in charge are needed within the ambulance care]. PMID- 1881206 TI - [The new law on psychiatric compulsory treatment is hazardous for the public]. PMID- 1881207 TI - [Treatment of breast cancer has improved]. PMID- 1881208 TI - [It is hoped that the new regulations will improve the accuracy of the "cause of death" registry]. PMID- 1881209 TI - [An emergency surgery department can be staffed with non-specialists without obvious impairment of the quality of care]. PMID- 1881210 TI - [What are we going to do with all those crying children? "Happydrip" is the answer!]. PMID- 1881211 TI - [It is not unusual that severe infections can be related to implanted venous catheter systems]. PMID- 1881212 TI - [Preoperative staging of gastrointestinal cancer]. PMID- 1881213 TI - [Special clinics for treatment of adolescents with anorexia nervosa are needed]. PMID- 1881214 TI - [Anxiety depressions among the elderly--symptoms, diagnosis and treatment]. PMID- 1881215 TI - [Child-oriented interviews can result in good solution of the problems. Parents with acute psychiatric disorders need talks about their children's situation]. PMID- 1881216 TI - [Molecular genetics methods discovering the mechanisms of neoplasm etiology]. AB - The rapid advance in our understanding of cancer biology during the past decade, as exemplified by the discovery of oncogenes and tumour suppressor genes and their interactions in tumourigenesis, has revolutionized cancer research. This rapid progress has largely been due to the use of molecular genetics techniques. However, despite the wealth of available information as to the genetic basis of carcinogenesis, its clinical applicability remains limited. The review is a summary of the general principles and methods currently used to detect genetic alterations in neoplastic cells, with special emphasis on clinical applications. PMID- 1881217 TI - [Cowpox--a cat disease in man]. PMID- 1881218 TI - [A report from a prospective study. Chiari II malformation in children with myelocele]. PMID- 1881219 TI - [The men behind the syndrome. John Cleland, Hans Chiari and Julius Arnold--3 men behind a new phenomenon. Brain stem defects in children with myelocele]. PMID- 1881220 TI - [A police/scout of the clinic]. PMID- 1881221 TI - [Physician's role demands self-criticism]. PMID- 1881222 TI - [A report of activities as a steering system: simple and concrete but complete]. PMID- 1881223 TI - [Do bibliometric methods function as an evaluation of qualification?]. PMID- 1881224 TI - [Primary health care plays an essential role in the future care of cancer patients]. PMID- 1881226 TI - [Correctly used test packages are economic]. PMID- 1881225 TI - [Is weight fluctuation a risk factor?]. PMID- 1881227 TI - [The sterile needle--a symbol for prevention of infection transmission]. PMID- 1881228 TI - [Remarkable findings in compartment syndrome after surgery with the use of a leg support]. PMID- 1881229 TI - [Paracetamol in therapeutic dosages can cause severe hepatic and renal damage in alcoholics]. PMID- 1881230 TI - [Stricter rules for referral to PAD (pathologico-anatomical diagnosis) do not guarantee economic savings]. PMID- 1881231 TI - [Forensic psychiatrists must be more in agreement on the evaluation of juvenile delinquents]. PMID- 1881232 TI - [Better treatment with the new optimal length bandages]. PMID- 1881234 TI - [Neurology and theology--on the genesis of metaphysical anemia]. PMID- 1881233 TI - [The impulse activity in human nerves provides clues to the function of the nervous system]. PMID- 1881235 TI - [Kuwait after the war. Material damages are significant and health care services were destroyed]. PMID- 1881236 TI - [The role of district physicians in the detection and diagnosis of cancer]. PMID- 1881237 TI - Comparative specificity of plasma lecithin:cholesterol acyltransferase from ten animal species. AB - The molecular specificities of plasma lecithin:cholesterol acyltransferase (LCAT) from ten animal species have been compared. Using a reassembled high density lipoprotein containing a mixture of phosphatidylcholines, the relative rates of liberation of different species of cholesteryl ester were measured. All but two species of LCAT clustered according to one of three patterns of substrate specificity. The LCAT from six species, including human, did not transfer highly polyunsaturated fatty acyl chains. In addition, human LCAT transesterified saturated fatty acyl chains more effectively than unsaturated fatty acyl chains. We conclude that the structures of the active sites of the enzymes differ, and that this may be related to size constraints that prevent efficient binding of large bulky phosphatidylcholines. PMID- 1881238 TI - Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease. AB - The two major phospholipid classes, namely, phosphatidylethanolamines (PE) and phosphatidylcholines (PC), were studied in four different regions of human brain, i.e., in frontal gray matter, frontal white matter, hippocampus and in pons. The fatty acid (FA) compositions of these phospholipids were found to be specific for the different regions. PC contains mostly saturated and 18:1 FA, while PE is rich in polyunsaturated FA. Aging has no influence on the FA compositions, while in Alzheimer's disease (AD) PE is modified in all four regions, particularly in frontal gray matter and in hippocampus. The abundance of the major monounsaturated FA of PE, 18:1, is not significantly altered in Alzheimer's disease, but there is a substantial increase in the relative amounts of the saturated components 14:0, 16:0 and 18:0. This is paralleled by a decrease in the polyunsaturated FA 20:4, 22:4 and 22:6. It is not clear whether the changes observed are specific for AD. Changes in saturated/polyunsaturated FA ratio are likely to influence cellular function, which in turn may cause certain neural deficiencies. The findings do not support the hypothesis that AD reflects an accelerated aging process. PMID- 1881239 TI - Activation and solubilization by Triton X-100 of membrane-bound phospholipase D of rat brain. AB - In the present study, we examined the ability of detergents to stimulate and solubilize phospholipase D (PLD) of a particulate fraction of rat brain. PLD activity was assayed by measuring the [3H]choline produced from the exogenous substrate dipalmitoyl phosphatidyl[3H]choline (dipalmitoyl [3H]PC). In the absence of detergents, PLD activity was not detectable. Of the detergents examined, Triton X-100 was found to markedly enhance PLD activity, whereas other detergents including sodium deoxycholate, sodium cholate, CHAPS and Lubrol-PX caused only a small, if any increase in activity. Enhancement by Triton X-100 was maximal at 0.1-0.2% (w/v) and decreased at higher concentrations. The optimal pH was 7.1-7.3. Both Ca2+ and Mg2+ inhibited enzyme activity stimulated by Triton X 100 in a concentration-dependent manner. Triton X-100 effectively solubilized PLD from the particulate fraction of rat brain; more than 70% of the activity of the particulate fraction was extracted by 0.5-1.0% (w/v) Triton X-100. Furthermore, when the PLD activities in brains of three different species (rat, rabbit and bovine) were measured under optimal conditions, the activities were found to differ greatly. PLD activity was highest in rabbit brain, followed by rat and bovine brains; the activity in bovine brain was extremely low compared to the activities in rat and rabbit brains. We conclude that Triton X-100 is potentially useful for the purification of PLD and that rabbit and rat brains are the preferred sources. PMID- 1881240 TI - Lipid composition and peroxide levels of mucosal cells in the rat large intestine in relation to dietary fat. AB - To examine whether dietary fat alters membrane lipid composition and peroxidation of polyunsaturated fatty acids in "non-proliferative" and "proliferative" cells in the large intestine, Sprague-Dawley rats were fed diets providing a polyunsaturated-to-saturated fatty acid ratio of 1.2 or 0.3 at a high or low level of fat intake for a 25-day period. Cell populations were isolated and the effect of dietary fat on membrane polyunsaturated fatty acid content and peroxide levels was determined. Neither fat level nor fatty acid composition of diet influenced total cholesterol, total phospholipids, and percentage of phospholipid classes in membrane phospholipids. Feeding the high fat and/or high polyunsaturated-to-saturated fatty acid ratio diet increased polyunsaturated fatty acid content of mucosal cell phospholipids. Increase in polyunsaturated fatty acid content was paralleled by a decrease in the monounsaturated fatty acid content of mucosal cell phospholipids. Membrane content of total saturated fatty acids was not significantly affected by diet. Variation in phospholipid fatty acid composition between "non-proliferative" and "proliferative" cells was observed. Lipid peroxide levels in mucosal cell lipid fractions were altered by dietary fat treatment. Animals fed high fat diets, compared to groups fed low fat diets, exhibited higher membrane peroxide levels when results are expressed as nmol/mg protein. Higher peroxide levels were observed in mucosal cells for rats fed high polyunsaturated-to-saturated fatty acid ratio diets when results were expressed per nmol of phospholipid. It is concluded that changes in fat level and fatty acid composition of the diet alters the mucosal cell membrane lipid composition in the rat large intestine and influences susceptibility of mucosal cell lipid to peroxidation. Further research is required to delineate which dietary factors--fat level, polyunsaturated-to-saturated fatty acid ratio, or both--have a primary influence on the degree of lipid peroxidation. PMID- 1881241 TI - Effect of chronic glucagon administration on lipoprotein composition in normally fed, fasted and cholesterol-fed rats. AB - Male adult Wistar rats received daily (at 9 a.m. and 5 p.m.) 10 micrograms of zinc-protamine glucagon by subcutaneous injection for 8 days. Plasma cholesterol levels were decreased by 36% in fed rats, 33% in cholesterol-fed rats and by 55% in fasted rats. Lipoproteins were separated into 22 fractions by ultracentrifugation using a density gradient. Glucagon administration decreased the cholesterol content in all lipoproteins except low density lipoprotein (LDL1) (1.006-1.040) and very low density lipoprotein (VLDL) from cholesterol-fed rats. The main decrease (-57 to -81%) was observed in 1.050-1.100 g/mL lipoproteins (LDL2 and HDL2), which contained a large amount of apo E, while HDL3 cholesterol was not affected. Triacylglycerol levels were decreased only in chylomicrons and VLDL (-70%) of fed and cholesterol-fed rats, while plasma and lipoprotein triacylglycerol levels were not changed in fasted rats treated with glucagon. In normally fed rats glucagon administration increased by 42% the fractional catabolic rate of [125I]HDL2 while the absolute catabolic rate appeared to be unchanged. Glucagon seems to be a potent hypolipidemic agent affecting mainly the apo E-rich lipoproteins. Its chronic administration limits lipoprotein accumulation which occurs upon cholesterol feeding. PMID- 1881242 TI - The effect of dietary zinc deficiency on the lipid composition of the rat erythrocyte membrane. AB - The effect of dietary zinc deficiency in the rat on the lipid composition of the erythrocyte membrane was determined. Weanling male Wistar rats were fed an egg white-based diet containing less than 1.0 mg Zn/kg diet ad libitum. Control rats were either pair-fed or ad libitum-fed the basal diet supplemented with 100 mg Zn/kg diet. A zinc refed group was fed the -Zn diet until day 18 and then pair fed the +Zn diet until day 21. The voluntary feed restriction associated with dietary zinc deficiency resulted in erythrocyte membranes that had depressed phospholipid/protein and elevated cholesterol/phospholipid ratios. Similarly, all feed restricted groups had elevated 22-carbon n-3 polyunsaturated fatty acids (PUFA) and depressed 22-carbon n-6 PUFA concentrations in alkenyl-acyl and diacyl glycerophosphoethanolamine, phosphatidylserine and phosphatidylcholine; they also had depressed 24:2n-6 levels in sphingomyelin. The relative concentrations of phospholipids in the membrane was similar between -Zn and +Zn (ad libitum) groups; however, the -Zn group had significantly less phosphatidyl-serine relative to +Zn (pair-fed) controls. PMID- 1881244 TI - Observation of rat hind limb skeletal muscle during arterial occlusion and reperfusion by 31P MRS and 1H MRI. AB - 31P NMR spectra and 1H MR T1- and T2-weighted spin-echo images were concurrently observed in rat hind limb during arterial occlusion and following reperfusion. With arterial occlusion, phosphocreatine level decreased and inorganic phosphate (Pi) level increased in 31P NMR spectra. Intracellular pH's dropped as a function of time. Beta-ATP started to decrease in three hours. In six hours after the occlusion, any peaks other than Pi were scarcely detected. The signal intensities in the 1H MR images increased homogeneously in both T1- and T2-weighted conditions, but the changes were more profound with T2-weighted images. After the release of the arterial occlusion, the 31P NMR spectra recovered to the preischemic state in several hours. The 1H MR images during reperfusion showed characteristic heterogenous pattern. The signal intensities in the anterior tibial muscle and the gastrocnemius muscle remained high in T1-weighted condition and the intensities further increased in T2-weighted condition, while those in other parts returned to the preischemic level. These changes were found to be irreversible even 12 hr after the release. The high signal intensities suggested the increase of water in the extracellular compartment induced by so-called reperfusion injury. Multinuclear analysis using in vivo NMR was valuable to consecutively detect time-dependent and location-specific response in skeletal muscle during ischemia and reperfusion. PMID- 1881243 TI - Study on the lipid composition of aging Fischer-344 rat lymphoid cells: effect of long-term calorie restriction. AB - Long-term calorie restriction (LCR) is widely known to increase the survival rate of laboratory rodents and appears to retard the aging and senescence process. The present study was undertaken in Fischer-344 male rats maintained on ad libitum (AL) or LCR (40% less food intake than AL starting at 6 weeks of age). Age associated changes in the proliferative response of lymphoid cells to mitogenic stimuli were studied in relation to alterations in the fatty acid composition of adherent and non-adherent-enriched subpopulations of spleen cells. Increases in spleen cell long-chain highly unsaturated fatty acids (20:4, 22:4 and 22:5) were accompanied by decreases in linoleic acid (18:2) in aging AL-fed rats. However, LCR stabilized levels of 18:2 and prevented the rise in highly unsaturated fatty acids. In addition, LCR markedly modulated the fatty acid profiles of thymocytes and bone marrow cells. A 70% decline in concanavalin A (Con A) stimulated [3H]thymidine uptake of spleen cells from AL animals was normalized by LCR. Splenic reduced glutathione (GSH), a potential modulator of the mitogenic response, was unaffected by age and nutritional regimen. Thus, normalization of lymphoid cell fatty acid composition by LCR parallels the preservation of mitogenic responsiveness to Con A. PMID- 1881245 TI - Iron oxide nanoparticles for use as an MRI contrast agent: pharmacokinetics and metabolism. AB - The pharmacokinetics and metabolism of a new preparation of superparamagnetic iron oxide nanoparticles were evaluated by 59Fe radiotracer studies and histologic examination of mice liver and spleen tissues (light and transmission electron microscopy). In the first 30 min following IV injection of the product half of the dose injected remains in the blood, the other part being sequestered mainly by the mononuclear phagocyte system (MPS). In the first five days following IV administration of the nanoparticles, early metabolization of the iron oxide cores occurs, revealed by modification of their aspect in the lysosomes of Kupffer cells and macrophages of the splenic red pulp. The incorporation of 59Fe is then observed in RBC of the mice. These results are discussed in relation with the physicochemical properties of this new preparation of nanoparticles, and compared with current pharmacokinetic data concerning injectable particle systems. PMID- 1881246 TI - Globus pallidus alterations and brain atrophy in liver cirrhosis patients with encephalopathy: an MR imaging study. AB - Brain magnetic resonance (MR) was performed in 29 liver cirrhosis patients without (N = 10) and with hepatic encephalopathy (HE) of chronic recurrent (N = 10) and of chronic persistent (N = 9) type. Sixty percent of the patients with chronic recurrent HE and 100% of the patients with chronic persistent HE showed a bilateral and symmetrical hyperintensity of the globus pallidus in the T1 weighted images while the T2-weighted images were normal, suggesting the possibility of the accumulation of a paramagnetic compound in this brain area during HE. Other findings of the study were evidence of brain atrophy of mild or moderate degree in 70% of patients with chronic recurrent HE and in 77% with chronic persistent HE and patients with liver cirrhosis without HE appeared normal on MR examination. PMID- 1881247 TI - In vivo proton magnetic resonance spectroscopy studies of human brain. AB - In vivo localized proton magnetic resonance spectroscopy (MRS) studies of brain were performed on eighteen normal subjects using the stimulated echo (STE) sequence. The absolute concentrations and proton relaxation times of N-acetyl aspartate (NAA), total creatine (Cr) and choline (Cho) were estimated. The MRS data was quantitatively analyzed for repeatability and intersubject variability. Quantitative analysis indicates excellent spectral repeatability. Significant intersubject variations in [NAA] and [Cr] have been observed while the intersubject variability in [Cho] has been found to be fairly small. Significant intensity distortions have been observed for mixing times longer than 50 msec. PMID- 1881248 TI - Gd-DTPA adrenal gland enhancement at 1.5 T. AB - The change in relative signal intensity of normal adrenal glands in 31 patients was evaluated following bolus administration of 0.1 mmol/kg of gadolinium diethylenetriamine pentacetic acid (Gd-DTPA). A marked increase in relative intensity of greater than 300% was observed within 2.5 min following contrast administration upon comparison of pre- and postcontrast T1-weighted gradient-echo images (TR = 47 msec, TE = 13 msec, pulse angle 80 degrees). Significantly elevated relative intensities of 55% and 44% persisted on postcontrast T1 weighted spin-echo images obtained at further delay times averaging 8 and 20 min, respectively, when compared to the identical precontrast sequence. PMID- 1881249 TI - NMR imaging study of the pharmacodynamics of polylysine-gadolinium-DTPA in the rabbit and the rat. AB - The pharmacodynamics of polylysine-(Gd-DTPA) (Schering, Berlin, Germany), a new blood pooling contrast agent for MRI, were studied in the rabbit and the rat. Polylysine-(Gd-DTPA) is a compound with high LD50. Due to its high molecular weight (50.000) and physico-chemical properties, it remains in the vascular system; during the first hour, the plasma level is three times higher than for Gd DTPA. MRI was performed at 1.5 T using a SE sequence with TR/TE = 300/15 or 20 msec. Signal intensities of muscle, liver and kidney were measured before and after intravenous injection of the contrast agent (0.1 mmol/kg) during 8 hours in the rat (n = 3) and up to 2 wk in the rabbit (n = 3). A dose response study in three additional rabbits confirmed that the 0.1 mmol/kg dose was optimal. The pharmacodynamics results show that the effects of polylysine-(Gd-DTPA) are similar in both the rabbit and the rat. The liver signal is enhanced by about 60% immediately after injection in both species. This enhanced signal decays to half its maximal value in about one hour, which makes the contrast agent useful for clinical applications at a dose of 0.1 mmol/kg. In the kidney medulla and cortex the signals are enhanced by much larger factors (about 3 to 4); it takes at least one day for the kidney to clear the contrast agent in both species. PMID- 1881250 TI - Short TI short TR inversion recovery imaging using reduced flip angles. AB - In this paper the effects of reducing the flip angle of the 90-degree observation pulse in inversion recovery imaging are described and analyzed. When incorporated in an IR sequence with a short inversion time (STIR), reduction to the 90-degree pulse allows a significant shortening of the repetition time without loss in contrast, although at the expense of some signal/noise. The generalized STIR sequence thus combines the previously reported advantages of a conventional STIR sequence--suppression of ghost artifacts from abdominal wall movement, suppression of chemical shift and boundary artifacts, additive effects of N(H), T1 and T2 on image contrast--with reduced power deposition and the advantages resulting from shorter repetition times, viz, single heart-beat triggering, increased number of signal averages for suppression of motion artifacts, acquisition of interleaved contiguous slices without cross-talk or considerable time savings when the number of required slices is limited. The proposed method is demonstrated and experimentally verified by imaging experiments on phantoms and human subjects. In principle the method is applicable to all cases where STIR imaging has been proven to be successful. PMID- 1881251 TI - Magnetic resonance imaging of the surgically repaired meniscus: six-month follow up. AB - The appearance and rate of healing of sutured meniscal repairs in 17 patients were evaluated using magnetic resonance scans. While prior studies in animals and humans (1-4) suggest that complete healing can occur as early as 6 wk postoperatively, we found that at 7 wk 15/15 patients demonstrated meniscal defects at the site of repair. At 6 mo, 11/11 patients showed persistent signal abnormalities. Two patients scanned at 11-12 mo also had defects at the site of repair. Therefore, complete meniscal healing appears not to occur as early as previously believed. This may affect decisions regarding the type of suture material used, the surgical treatment of associated injuries and the postoperative rehabilitation regimen. As defects may be present for relatively long periods of time following meniscal repair, caution must be exercised when attempting to diagnose new or recurrent tears in these patients. PMID- 1881252 TI - Cardiac MRI cine and color Doppler in valvular disease: correlative imaging. AB - Cardiac cine field echo MRI and color Doppler were performed in 13 patients with aortic regurgitation (n = 4) or multiple valvular diseases (n = 9). The size, shape, and direction of regurgitation jets correlated well. Color Doppler was better able to follow flow jets in oblique planes. Cine MRI was better able to evaluate patients with marked cardiac dilatation. PMID- 1881254 TI - Applications of chemical-shift-selective NMR microscopy to the non-invasive histochemistry of plant materials. AB - Chemical-shift-selective imaging at microscopic resolution has been applied to the study of various plant materials including orange peel, grape berries and both dried and undried fruits of fennel. It is shown that selective imaging of aromatics and carbohydrates as well as water and oil can be performed with in plane resolution down to 13 microns and slice thicknesses of 1 mm or less, at a field strength of 4.7 Tesla. The noninvasive nature of the method gives it advantages over established methods of plant histochemistry which involve sectioning and staining to reveal different chemical constituents. PMID- 1881253 TI - Spinal MR imaging in suspected metastases: correlation with skeletal scintigraphy. AB - Bone scintigraphy (RN) and magnetic resonance imaging (MR) were prospectively and retrospectively correlated in 64 patients with suspected spinal metastatic disease and possible spinal cord compression. Images were retrospectively interpreted and compared with the prospective official RN and MR reports to help decide relative prospective lesion conspicuity. Spinal lesions were confirmed by radiography, computed tomography, myelography or MR and RN follow-up in 56 patients (88%). Prospectively, MR detected 11 lesions not reported on RN while RN detected two lesions not reported on MR. Retrospective review of RN detected six lesions previously not reported. Retrospectively MR showed all lesions. Those lesions seen only in retrospect by RN were rather subtle and would be difficult to detect prospectively. In general, lesions not well seen on RN had relatively more bone marrow abnormality and less cortical bone involvement. In some cases, MR imaging shows spinal marrow lesions not well seen on planar RN. PMID- 1881255 TI - Magnetic resonance imaging in a model of atherosclerosis: use of a collar around the rabbit carotid artery. AB - Transverse cardiac-cycle gated high resolution magnetic resonance images have been obtained from the neck of the New Zealand white rabbit both in normal animals and from those in which a collar had been earlier positioned around one carotid artery. The study included animals fed on normal and on high cholesterol diets with the surgical modification having been demonstrated previously to cause a rapid and reproducible lesion resembling early atherosclerosis. The aim of the work was to investigate the attainable spatial resolution and sensitivity at a field strength of 2 T using a large radiofrequency transmitter system and a surface coil receiver with which spin-echo images have been obtained. Visualization was enhanced using a three-dimensional interpolation technique. An image resolution of 200 microns was readily obtained but was shown to be insufficient for delineating pathological features within the artery wall such as intimal layer thickening. The results have been compared with histopathological findings which confirmed that any morphological changes were within the pixel resolution of the image. Extensions to the methodology are proposed which should be able to detect atherosclerotic changes with a resolution of 50 microns within a feasible imaging time. In addition, the MRI study of how the surgical intervention alters the artery shape and curvature was carried out and the MRI demonstrated that collar implantation in general does not occlude the artery and causes only a slight and gradual degree of curvature to the vessel. PMID- 1881256 TI - Gadolinium-labeled liposomes containing amphiphilic Gd-DTPA derivatives of varying chain length: targeted MRI contrast enhancement agents for the liver. AB - Paramagnetic liposomal contrast agents were synthesized and utilized for selective augmentation of T1 MR imaging of the livers of normal Balb/c mice. Amphiphilic gadolinium complexes, which mimic phospholipids, were incorporated into the lamella of small unilamellar liposomes (SUV) such that they become an integral part of its surface. The amphiphilic complexing agents consisted of DTPA reagents in which a pair of alkyl chains of varying lengths are attached via amide linkages. The in vivo lifetimes of the amphiphilic agents were found to be dependent on the chain length of the alkyl groups. PMID- 1881257 TI - Technical variables influencing the detection of acute deep vein thrombosis by magnetic resonance imaging. AB - To establish which technical variables influence the detection of deep vein thrombosis by magnetic resonance imaging, 2 dogs, 5 normal volunteers and 17 patients were studied using a 1.5 T whole-body system. A sequential slice gradient echo acquisition (TR 25, TE 13, 0 = 30 degrees, 2 NEX, flow compensation rephasing gradients) in the axial plane was found to be optimal for detecting venous thrombosis. Thus, when using appropriate technique, MRI may identify deep venous thrombosis accurately. It may also allow the diagnosis of conditions which may simulate venous thrombosis clinically since the most common of these, ruptured Baker's cyst, cellulitis, muscle tear, hematoma and external venous compression are all readily identified by MRI. PMID- 1881258 TI - Limited field of view spin echo MR imaging. AB - Several groups have reported using a method of limiting the field of view (FOV) where the slices excited by the 90 and 180 degree pulses are perpendicular. However, only one slice can be excited during each repetition time, so multislice imaging is not possible. We present a modification of this method that allows multislice imaging. The slices excited by the 90 degrees and 180 degrees pulses are at a small angle; the field of view is limited and multislice imaging is possible. The modifications also allow the center of the FOV to be offset to any position. We describe the conditions that yield optimal images for the given FOV, slice thickness, and interslice gap. Representative images demonstrating the features of the technique are presented. The technique can be used to reduce the number of phase-encoding steps resulting in reduced imaging time, or it can be used to increase the spatial resolution without increasing the imaging time. PMID- 1881259 TI - Generalized electrical analysis of low-pass and high-pass birdcage resonators. AB - The radio-frequency 'birdcage resonator' has found wide use in MRI/MRS for its field homogeneity and signal-noise characteristics. This paper presents a general analysis, derived from lumped element transmission line theory, of the electrical behavior of unloaded, N-column birdcage resonators applicable to several versions of the basic design including low-pass and high-pass coils. Analytic expressions and computer results are presented for both types of coil describing resonant frequencies, input and characteristic impedances, dispersion relations, pass bands, resonant peak bandwidth and Q. Theoretical expressions for normalized resonant frequency difference ratios independent of element values and resonator geometry have been developed for generic low- and high-pass coils. Experimental measurements of resonant frequencies were made for six coils, and the average agreement with theoretical predictions was approximately 4%. PMID- 1881260 TI - Reaction of gadolinium chelates with endogenously available ions. AB - The extent of reaction of 153Gd-radiolabeled Gd(L) chelates with 25 mM CO23- (25 mF), PO34-, Zn2+ and Cu2+ at pH 7 was determined for L = EDTA, DTPA, DOTA, HP DO3A, and DO3A. Gd(EDTA)- and Gd(DTPA)2- reacted (greater than 20% in 10 min) with Cu2+ and Zn2+ in the presence of PO34-. These double replacement reactions yielded precipitated GdPO4 and chelated Cu(L). Gd(HP-DO3A), Gd(DO3A) and Gd(DOTA) were inert to reaction with all four ions at room temperature (less than or equal to 1% reaction detected). The thermodynamic binding constants of the ligands for Gd3+ and Cu2+ were found to be equal (10(20) M-1) for DO3A, while DOTA and HP-DO3A favored Gd3+ over Cu2+ by greater than or equal to 10(2) M-1. The low order of reactivity of Gd(DOTA)- and Gd(HP-DO3A) was anticipated by the binding constants, but the lack of reactivity of Gd(DO3A) is attributed to kinetic inertia. This latter property, desirable in MRI contrast agents, is promoted by the conformational stability of the tetraazacyclododecane macrocycle, which forms the backbone of the ligand. It is concluded that this class of chelates is exceptionally inert in solutions of endogenously available ions, and that thermodynamics alone is an insufficient predictor of the reactivity of the highly inert Gd complexes based on the tetraazamacrocycle. PMID- 1881261 TI - An MRI tissue equivalent lesion phantom using a novel polysaccharide material. AB - A new polysaccharide material, TX-150, and method is described which will potentially allow formation of stable, multi-compartment MRI phantoms constructed without intervening septa. TX-150 can be made into water based gels which are nominally tissue equivalent. Although contiguous regions of different water content are not possible, as water diffusion will occur until equilibrium is reached, TX-150 gel T1 and T2 values can be adjusted independently, while maintaining a constant water composition, by appropriate additives. Unlike paramagnetic ions and chelates, metal phthalocyanines have been found to bind tightly to TX-150, thus, permitting formation of stable contiguous regions of differing T1 relaxation properties. Phantom T2 values can be effectively modified with 2-2-diphenyl-1 picrylhydrazyl, which has little affect on gel T1 values, to form septumless lesion phantoms of varying T1 and T2. PMID- 1881262 TI - Magnetic resonance imaging of hyperbaric oxygen treated rats with spinal cord injury: preliminary studies. AB - Magnetic resonance imaging (MRI) has been performed to assess the efficacy of hyperbaric oxygen (HBO) treatment on experimental spinal cord injury in a rat animal model. A moderately severe injury, similar to Type III injury seen in humans (Kulkarni et al. Radiology 164:837;1987) has been chosen for these studies. An improvement in the neurologic recovery (based on Tarlov scale) has been observed following HBO treatment over a period of 72 hr. Based on MRI, HBO treatment appears to arrest the spread of hemorrhage and resolve edema. PMID- 1881263 TI - In vivo proton magnetic resonance imaging and localized spectroscopic analysis of polycystic kidney disease in DBA/2FG-pyc mice. AB - Proton magnetic resonance imaging (MRI) and localized spectroscopy techniques were used to study polycystic kidney disease (PKD) in DBA/2FG-pcy (pcy) mice, which are an animal model for the adult form of human PKD. A volume selective spectroscopy (VOSY) method was used to obtain localized proton spectra as well as apparent T1 and T2 relaxation times of the kidneys of either pcy or DBA/2FG normal (DBA) mice. Localization of the proton spectra was based on spatial coordinates determined from the proton images. Increases in apparent kidney T1 and T2 relaxation times were observed for pcy mice in comparison to those measured in DBA mice. Localized kidney T1 values from pcy mice were found to range from 799 to 1395 msec whereas DBA mice kidney T1 values were 617 to 774 msec. Localized T2 values measured from pcy mice kidneys ranged from 90 to 172 msec in comparison to kidney T2 values of 50 to 72 msec for DBA mice. The onset of cyst formation in the kidneys of pcy mice as a function of age was also studied. As early as 4 to 5 weeks of age it was possible to detect in vivo changes in pcy mice kidney T1 and T2 values. PMID- 1881264 TI - Optimized pulse sequences for magnetic resonance measurement of aortic cross sectional areas. AB - This study was done to improve the ability of magnetic resonance (MR) imaging to provide clear cross-sectional images of the ascending and descending aorta in diastole. The study was motivated by interest in measuring the regional compliance of the ascending aorta, which requires determination of the change in cross sectional area of the vessel between systole and diastole. In diastolic images, residual signal from slow flowing blood and flow artifact consistently obscured the inner boundary of the aortic wall and precluded tracing and measurement of the cross sectional area. We concluded that cross sectional area measurement of the ascending aorta was impossible on our system using standard spin echo sequences. To improve wall delineation in diastolic images, SAT pulses were optimized with respect to pulse timing, slice thickness, and gap. Optimized SAT pulses greatly improved the delineation of the vessel wall by removing unwanted signal from flowing spins. Measurement precision was vastly improved by running two scans with and without flow compensation, and correlating visually and numerically the area measurements from each. We established that each image should be measured by two independent observers and traced three times by each. Using these procedures, diastolic cross-sectional areas of the mid-ascending aorta could be measured with a precision of 2.5%, and the change of cross sectional area between systole and diastole could be measured with a precision of 10.8%. These measurements were precise enough to detect CAD patients with low aortic compliance from the age-matched controls previously reported in one study. The test based on cross sectional area measurement, with a false positive detection rate of 5%, had a false negative rate of 58%. Compliance measurements by MR at 1.5 T could become clinically useful if normal and abnormal populations are sufficiently separated. PMID- 1881265 TI - Relationship of hippocampus and amygdala to coronal MRI landmarks. AB - Magnetic resonance imaging is playing an increasingly important role in the evaluation of the hippocampus, particularly in epilepsy, schizophrenia, and Alzheimer's dementia. Because of the complex configuration of the hippocampus, it is difficult to compare from patient to patient. We developed a system to allow comparison of the hippocampus on coronal images. We performed 34 magnetic resonance studies on 29 normal subjects. Ten anatomic landmarks were identified. These landmarks have a consistent 5-mm periodicity regardless of usual head flexion. In the second phase of our investigation, we showed that the amygdala, hippocampal head, hippocampal body, and hippocampal tail have a consistent relationship to the coronal magnetic resonance imaging landmarks. PMID- 1881266 TI - Magnetic resonance imaging of a post-traumatic arteriovenous fistula in the lower extremity. AB - Currently, magnetic resonance (MR) is most useful as a means of providing distinct images of gross abnormalities in major blood vessels. While new advances and further refinements will continue, MR has proven its value as a convenient and effective diagnostic tool for the recognition and delineation of vascular abnormalities, such as acquired arteriovenous fistulae (AVFs). We report a case of a chronic, post-traumatic AVF, in which MR angiography provided excellent anatomic detail and angiographic correlation. PMID- 1881267 TI - MR imaging of degenerative disorders of brainstem and cerebellum. PMID- 1881268 TI - Quality assurance, knowledge-based systems, and machine learning. PMID- 1881269 TI - Do physicians have a bias toward action? A classic study revisited. AB - In an attempt to replicate the findings of a classic study of medical decision making, the authors studied decision making in modern pediatrics practice. They prepared case scenarios and surveyed pediatricians for three common clinical decisions: tympanostomy tube placement, radiography orders, and emergency room referrals. Initial reviewers rated the cases according to the likelihoods that they would take the clinical actions mentioned. Subsequently, other physicians presented with a subset of scenarios in which the initial reviewers were least likely to act tended to be more active in the tympanostomy (p = 0.004) and radiography (p = 0.076) decisions. In these cases the physicians appeared to have a bias toward action. For a subset of scenarios in which the initial reviewers were most likely to act, subsequent reviewers were neither more nor less likely to act than the initial reviewers. PMID- 1881270 TI - Availability, wishful thinking, and physicians' diagnostic judgments for patients with suspected bacteremia. AB - A prospective cohort study was done to assess the effects of value bias and the inappropriate use of the availability heuristic on physicians' judgments of the probability of bacteremia. Subjects of the study were 227 medical inpatients in a university hospital who had blood cultures done. Estimates of the probabilities that individual patients would have positive blood cultures were collected from the house officers who ordered the cultures. Clinical data and culture results were also obtained. Based on the data the authors calculated "value variables," reflecting doctors' assessments of the risks that individual patients would die in the hospital if they were to have bacteremia. "Recalled experience variables" reflected the doctors' recollections of recent experiences with patients with bacteremia. The physicians significantly overestimated the likelihood of bacteremia for most of their patients. Their ROC curve for this diagnosis showed moderate discriminating ability (area = 0.687, SE = 0.073). Two recalled experience variables were significantly associated with the physicians' probability estimates. The value variables were significantly inversely associated with them. These relationships were independent of several clinical variables and measures of disease severity. The physicians' intuitive diagnostic judgments were thus influenced by the availability heuristic and by wishful thinking, a form of the value bias. The availability heuristic may mislead physicians by causing them to believe that random variations in the prevalence of a nonepidemic disease represent real trends. Wishful thinking may lead physicians to underestimate the likelihood of a disease for patients most at risk for its consequences. Teaching physicians to develop better judgmental strategies may improve the quality of their judgments and hence their patient care. PMID- 1881271 TI - Cognitive psychology and medical judgment: some downfalls of studying pitfalls. PMID- 1881272 TI - Using the ID3 algorithm to find discrepant diagnoses from laboratory databases of thyroid patients. AB - Rare cases are a central problem when an expert system is constructed from example cases with machine learning techniques. It is difficult to make a decision support system (DSS) to cover all possible clinical cases. An inductive learning program can be used to construct an expert system for detecting cases that differ from routine cases. The ID3 algorithm and the pessimistic pruning algorithm were tested in this study: a DSS was built directly from the data of patient records. A decision tree was generated, and the cases misclassified by the decision tree as compared with the classifications of a clinician were listed on a checklist, which formed the feedback to the clinician. In clinical situations about 5-10% of functional thyroid disorders may be misclassified. At this error level, the method found over 90% of the errors with a specificity of 95%. In simple medical classification tasks this dynamic self-learning system can be used to create a DSS that can assist in the quality control of clinical decision making. PMID- 1881273 TI - Psychological androgyny and preference in loss-framed gambles of medical students: possible implications for resource utilization. AB - Physician decisions concerning allocation of health care resources to patients are highly variable and poorly understood. Psychological androgyny theory (PAT) has been employed as a model of the interpersonal and task activities required of physicians for care of their patients. Several studies have successfully predicted physician resource utilization using measures derived from PAT. Using a sample of 97 first-year medical students, the authors explored the relationship between PAT and risk preference in loss-framed gambles in order to elucidate the process whereby variables derived from PAT predict resource utilization. As hypothesized, students selecting the certain loss had significantly higher mean androgyny scores than did students selecting uncertainty. Research involving these constructs is integrated in the context of a theoretical "causal model," which highlights issues deserving of future research. PMID- 1881274 TI - Benign and malignant breast disease: the relationship between women's health status and health values. AB - The study purpose was to determine whether differences in the weights assigned to various dimensions of health by 90 women in three subgroups (benign breast disease, breast cancer receiving chemotherapy, and breast cancer receiving other therapies) were associated with differences in self-reported health status in these dimensions. Two methods, one direct and the other indirect, were used to elicit values for mobility, depression, and social support. Two different scales also provided self-reports of health status in each of these dimensions. These measures, in conjunction with sociodemographic variables, were used to test for status-value relationships. No statistically significant association between health values and health status was observed. The absence of any detectable association may have been a result of methodologic difficulties in assessing broadly defined dimensions of health. A possible solution would be to use "individualized" dimensions that are uniquely important to the individual, and to take into account such factors as possible influences of past health status and values, and possible gaps between expected health status and health status actually experienced. PMID- 1881275 TI - Use of clinical judgment analysis to explain regional variations in physicians' accuracies in diagnosing pneumonia. AB - The authors sought to explain regional differences in physicians' accuracies in diagnosing pneumonia by prospectively studying emergency department patients at three sites and analyzing differences in physicians' diagnostic strategies and patient characteristics. They enrolled 1,119 Illinois patients, 150 Nebraska patients, and 142 Virginia patients presenting with fever or respiratory symptoms for whom physicians ordered a chest radiograph because of suspicion of pneumonia. Emergency department physicians recorded patients' clinical findings and estimated the probability that a chest radiograph would show pneumonia. A measure of accuracy, the correlation between physicians' probability estimates and actual outcomes, was 0.41 (95% CI 0.36-0.46) at Illinois, 0.66 (95% CI 0.54-0.75) at Nebraska, and 0.55 (95% CI 0.42-0.65) at Virginia. Physicians' strategies at the three sites differed markedly in their weightings of asthma, signs of consolidation, cough, tachypnea, age, and gender. These differences in weighting paralleled differences in the optimal clinical strategies derived from patient data at the three sites. Differences in diagnostic accuracy were best explained by differences in the difficulties of diagnosing pneumonia in the populations. Physicians at each site used clinical findings in a way that was close to optimal for their location. This type of analysis provides a new tool for understanding the sources of regional variations in clinical practice. PMID- 1881276 TI - Scotched on the ROCs. PMID- 1881277 TI - Diamond's correction method--a real gem or just cubic zirconium? PMID- 1881278 TI - Verification bias and the one-parameter logistic ROC curve--some clarifications. PMID- 1881279 TI - The influence of positive affect on clinical problem solving. AB - This study investigated the influence of positive affect, induced by report of success on an anagram task, on medical decision making among third-year medical students. The subjects were asked to decide which one of six hypothetical patients, each of whom had a solitary pulmonary nodule, was most likely to have lung cancer. They were asked to verbalize their clinical reasoning as they solved the problem. The positive-affect and control groups did not differ in the tendency to make a correct choice, but subjects in the positive-affect condition were significantly earlier in identifying their choices. These subjects were also significantly more likely to go beyond the assigned task, expressing interesting in the cases of the other patients and trying to think about their diagnosis, even though that task was not assigned. The positive-affect subjects also showed evidence of configural or integrative consideration of the material to a reliably greater extent than did control subjects, and there was significantly less evidence of confusion or disorganization in their protocols than in those of controls. These findings are compatible with earlier work suggesting a different organizational process and greater efficiency in decision making among people in whom positive affect had been induced, and with recent work suggesting that positive affect facilitates flexibility and integration in problem solving. They also indicate that these effects may apply to the problem-solving strategies of professionals in clinical problem-solving situations. PMID- 1881280 TI - [The psychic status and work capacity of the victims of the accident at the Chernobyl Nuclear Power Station in the period of recovery from and near-term consequences of acute radiation sickness]. AB - Analysis of the results of clinicopsychological investigation of persons developing ARS (I-III degree of severity) as a result of the Chernobyl accident has shown that 4-6 mos. after the exposure the psychic status and mental working ability of the affected persons showed close correlation with a degree of ARS. In 12-18 mos. profession and adequate employment played a decisive role in the formation of unfavorable psychic conditions and limited working ability. Later on in 2.5-3 years after exposure a decrease in psychic working ability, the development of unfavorable psychic conditions was noted more frequently in patients with ARS of more severe types and in examinees of older age. At all stages of rehabilitation personality traits of the affected persons play an important role in the revival of working abilities. PMID- 1881281 TI - [The labeling index of parenchymal and stromal tumor cells--an index of radiosensitivity and prognosis of laryngeal cancer]. AB - Biopsy specimens were taken from 130 laryngeal cancer patients and investigated before treatment. Autoradiography with 3H-thymidine was used to determine the labeling index (LI) of parenchymal cells and tumor stroma. Squamous cell carcinoma was diagnosed in all the cases. Altogether 41 patients were irradiated at a total focal dose of 32-40 Gy and underwent surgery. A full course of radiotherapy at a total dose of 52-60 Gy was given to 89 patients, however recurrences were detected in 38. Comparison of the therapeutic results and indices of proliferative activity of tumor cells has shown: 1. interrelationship of Ll of parenchymal cells and LlI of tumor stromal cells; 2. a tendency to correlation was revealed between indices of LI of parenchymal and stromal cells and a stage of disease; 3. correlation between a degree of a decrease in LI of parenchymal cells and completeness of tumor regression in the course of therapy was shown; 4. LI of stromal cells in the patients' tumors with resumption of tumor growth was lower (0.8) than in patients without resumed growth. PMID- 1881282 TI - [The immediate results of the use of isometronidazole in the combination therapy of patients with lung cancer]. AB - The paper is devoted to assessment of isometronidazole tolerance, used as a radiosensitizer for preoperative irradiation of lung cancer patients, and to characterization of morphological postradiation changes in tissues of carcinomas removed at operation. Isometronidazole was shown to cause no severe side-effects in patients, improving considerably radiation injury of the tumor parenchyma. PMID- 1881283 TI - [Quantitative assessment of the computed tomographic characteristics of the brain in neuro-geriatric diseases. I]. AB - The paper is devoted to a study of the combined use of linear, volumetric, volumetric lobar and densitometric indices of computerized tomography of the brain in patients with neuro-geriatric pathology. Methods of quantitative assessment of CT scans were described. The interrelationship of linear, volumetric and volumetric lobar CT parameters and densitometric indices in middle aged and old patients was shown. A number of linear and densitometric parameters was recommended for clinical practice and research. PMID- 1881284 TI - [The effect of age and sex on the quantitative parameters of the computed tomography of the brain in neuro-geriatric diseases. II]. AB - The paper is devoted to a study of age and sex differences of linear, volumetric, volumetric longitudinal and densitometric parameters of CT of the brain in patients with neurogeriatric diseases with chronic cerebrovascular insufficiency. The ventricular system of the brain and subarachnoid space was shown to increase with age; a decrease in the relative density of the white substance at the anterior horns was noted. Sex differences were most noticeable in younger patients. Average sizes of the ventricular system and subarachnoid space were indicated for men and women belonging to different age groups. A conclusion was made that assessment of CT results in neurogeriatric patients must include their age and sex. PMID- 1881286 TI - [Infusion dynamic uretero-scintigraphy in the evaluation of the functional status of the ureter and pelvis]. AB - A proposed new method of infusion dynamic ureteroscintigraphy was used for investigation of 51 controls and 27 patients with unilateral tuberculous ureterohydronephrosis. Values of the contractility of different parts of the ureters and pelvis were obtained. The statistic law of distribution of these values is logarithmically normal. A high sensitivity of the method in the assessment of ureteral and pelvic function was shown. PMID- 1881285 TI - [Radioimmunologic analysis in the differential diagnosis of cancer of the thyroid gland]. AB - Investigations using a radioimmunoassay in 92 patients with nodular goiter, thyroid adenoma and cancer have shown that changes in the levels of T4, T3 and TSH cannot be used in differential diagnosis of tumors. A high level of thyroglobulin (TG) in 70-75% of patients in the absence of antibodies to it and the presence of a "cold node" on a scan is suggestive of differentiated types of thyroid cancer. In these cases TG can serve as a tumor marker. A moderate level of Tg in 25-30% of cases against a background of a high level of antibodies to it does not permit its use as a tumor marker in such patients even in the postoperative period. High levels of TG and TSH despite the use of thyroid drugs in patients, operated on for differentiated types of thyroid cancer, may be suggestive of a possible manifestation of a recurrence or metastatic spreading. PMID- 1881287 TI - [The behavior of radioactive albumin microspheres on administration into the hepatic artery of animals]. AB - A study was made of the behaviour of human serum albumin microspheres--SAM-- (USSR) during intraarterial selective infusion of them in the hepatic artery of rabbits. 125I was used as a radioactive tracing agent. Accumulation of the agent in organs and its excretion were investigated over time by radiometry in vivo and in vitro. Distribution of 125I-SAM in the liver at administration of different amounts of the radioactive drug was also investigated. A mathematical formula of calculation of the optimum amount of administered microspheres was proposed. A conclusion was made of a possibility of the use of the SAM as a carrier of short lived radionuclides for endovascular radiotherapy of malignant hepatic tumors. PMID- 1881289 TI - [Control of the radiation protection of medical personnel during transcutaneous nephro-ureterolithotomy]. AB - The authors describe methods to ensure radiation safety of medical personnel, used in transcutaneous nephro-ureterolithotomy. The results of measurements of an exposure dose rate and calculations of an equivalent dose are presented. They do not exceed standard maximum permissible doses. PMID- 1881288 TI - [Functional status of the pituitary-thyroid system in children and adolescents exposed to radiation as a result of the accident at the Chernobyl Nuclear Power Station]. AB - The paper is concerned with the results of a follow-up over the period of 1986 1989 of function of the hypophyseo-thyroid system in children and adolescents (approximately 6000 persons), residing in the South-West of the Kaluga Region, where radiation fallouts were observed after the Chernobyl accident. The results were based upon the analysis of medical examinations and determination of the blood levels of TSH, T4 and T3. A certain functional activation of the thyroid system was observed in a majority of the examinees. A conclusion has been made of a necessity of a long-term follow-up of the thyroid of persons who received radioactive iodine in childhood. PMID- 1881290 TI - [Chronic cough]. PMID- 1881291 TI - [Acute chest pain]. PMID- 1881292 TI - [Systematization of types and methods of radiotherapy, methods and methodology of irradiating patients]. AB - The paper is concerned with the principles of systematization and classification of radiation therapy, approaches to the regulation of its terminology. They are based on the distinction of the concepts of radiation therapy and irradiation of patients. The author gives a concise historical review of improvement of the methodology of radiation therapy in the course of developing of its methods and facilities. Problems of terminology are under discussion. There is a table of types and methods of radiation therapy, methods and techniques of irradiation. In the appendices one can find a table of typical legends and examples of graphic signs to denote methods of irradiation. Potentialities of a practical use of the system are described. PMID- 1881293 TI - [Comparison of different methods of imaging in determining the resectability of liver metastases in colon cancer]. PMID- 1881294 TI - [Clinical magnetic resonance spectroscopy]. PMID- 1881295 TI - The efficacy of ethnomedicine: research methods in trouble. AB - One of the tasks of medical anthropology is to conduct research to evaluate the efficacy of traditional health care practices. The benefits of health care may be evaluated in numerous ways, but in this article we examine only the problem of how to determine whether a therapeutic intervention changes the pathophysiology of a disease. The randomized controlled trial is acknowledged as an ideal that will rarely be attainable by medical ethnographers. Individual case studies are primarily useful for hypothesis formation. We are left then with observational studies (case series) as a feasible and useful alternative. Those presently in the anthropological literature are examined and each is found to be flawed to some extent. Future investigations can profit from what was learned in these pioneer studies by giving more attention to patient selection, treatment description, and objective measures of outcome. PMID- 1881296 TI - An Ayurvedic theory of cancer. AB - Ayurveda is a healing system widely practiced throughout South Asia. It is founded upon a set of Sanskrit texts composed two thousand years ago which describe in detail a theory of humoral balance within the body. The name Ayurveda means "that which has been seen to be true about long life." In 1975 in southern Tamil Nadu, an aged practitioner of Ayurveda conducted for the author's benefit a series of lectures about cancer, in which he propounded his own idiosyncratic theory regarding the nature of this disease. The doctor's lectures were a linguistic and topical pastiche, melding Indian and Western biologies, psychologies, and sociologies. The lectures were fascinating for they demonstrated many lines of kinship between ideas expressed in the ancient Sanskrit texts and ideas afloat still in the modern world. But for all their richness Mahadeva Iyer's lectures were seemingly unfocused, and his motives for developing them were unclear to the author. Only when the author was able to see these lectures, not as cultural artifacts, but as messages addressed from one historically situated personality to another, did the reason for the doctor's conveyance of them to her become clear. PMID- 1881297 TI - Ethnomedicine: diverse trends, common linkages. PMID- 1881298 TI - An epidemiological description of a folk illness: a study of empacho in Guatemala. AB - Although anthropologists have provided descriptions of many folk illnesses, few have systematically evaluated their prevalence and determined who is at greatest risk for acquiring them. This report attempts to provide a systematic description of the folk illness empacho including the symptoms that define it. Illness prevalence was estimated and subpopulations at greatest risk were identified from illness histories collected from a random sample of households in rural Guatemala. Empacho was found to constitute a distinct cluster of symptoms: diarrhea, vomiting, headache, and lack of appetite. It differed from other gastrointestinal illnesses in that headaches were more likely and stomachaches were less likely to be reported. Empacho was highly prevalent and occurred in adults and children. Further, results showed that although empacho was frequently diagnosed by residents, folk healers were rarely consulted for any illness. Nevertheless, a strong association exists between a household diagnosis of empacho and the use of folk healers by those households (p less than .001). PMID- 1881299 TI - Discourse, dano, and healing in north coastal Peru. AB - This paper argues that discourse is culturally recognized as powerful and dangerous, significantly informing both the illness experience known as dano (magical aggression) and its traditional cure in North-coastal Peru. Words are viewed as a type of symbolic currency which negotiate and "transact" identity in an economic, social, and psychological environment in which self-esteem is generally viewed as a scarce commodity and tied to the opinions of others. In the case presented, gossip is a verbal mode of dano that is perceived as a threat to the victim's constructed identity: the physical and emotional symptoms of dano directly relate to the anxiety about what people will say (que diran). I examine the symbolism of the mesa or traditional healing ceremony in terms of this "economy" of discourse to illustrate how the patient's personal experience is linked to a culturally powerful metaphor and then transformed in order to effect the cure. PMID- 1881300 TI - Deciding how to decide: possession-mediumship in Jalari divination. PMID- 1881301 TI - Malay medicine, Malay person. PMID- 1881302 TI - The harp that plays by itself. PMID- 1881303 TI - Future directions in MRI of diffusion and microcirculation. Society of Magnetic Resonance in Medicine (SMRM) workshop. Bethesda, Maryland, June 7-8, 1990. PMID- 1881304 TI - NMR measurements of different tissue perfusion parameters. AB - The traditional perfusion rate is based on the amount of fluid flowing longitudinally down the capillaries, often given in ml/100 g tissue/min. In principle, fluid flowing radially out of or into the capillaries can be measured as well. Radial and longitudinal perfusion have the same units but independent values. If spins leave and reenter a capillary several times during a transit, radial perfusion can exceed longitudinal perfusion and it probably does. Radial perfusion measures capillary wall function. Progressively increasing the time between two gradient pulses in a proposed radial perfusion imaging sequence allows more magnetization to move into the vasculature to be dephased or removed. Progressive decreases in gradient strength keep diffusion effects constant allowing isolation of the desired perfusion effects. PMID- 1881305 TI - Diffusion of water in tissues and MRI. AB - The purpose of this paper is to present an overview of the diffusive behavior of water in biological tissues. The analysis shows that obstructive barriers would have to occupy very large volume fractions in order to account for the reduction in the diffusion coefficient (D) observed in biological systems. Generally, most models lead to the supposition that a substantial fraction (20-40%) of the cell water is hydration water, or that the diffusion coefficient of the cytoplasmic water is reduced substantially from the free water value. Thus, the conclusion that a substantial fraction of cell water has diffusive properties that are altered by the macromolecules of the cytoplasm seems inescapable. The impact of these findings on MRI remain to be determined. PMID- 1881306 TI - Functional variations in parenchymal microvascular systems within the brain. AB - Variations in microvascular system functions were observed among a number of brain areas. The rates of local blood flow varied 18-fold among areas and were extremely high in neuroendocrine structures. Marked differences in blood flow were also found within some brain structures. The volume of radiolabeled blood in perfused parenchymal microvessels ranged from 5 to 70 microliters/g and correlated closely with local cerebral blood flow. The hematocrits within parenchymal microvessels were 45-75% of the arterial hematocrit, which indicates that red cells more rapidly traverse brain microvessels than do plasma proteins. The mean transit times of blood through parenchymal microvessels were extremely short and ranged from 0.3 to 0.6 s. PMID- 1881307 TI - Intravoxel incoherent motion imaging using spin echoes. AB - The purpose of this paper is to review the basic principles of diffusion measurement with spin echoes. These principles can be combined with those of MR imaging to generate maps of diffusion coefficients. Diffusion imaging can be extended to imaging of other intravoxel incoherent motions (IVIM), such as blood microcirculation. Some of the technical problems encountered when implementing IVIM imaging are presented. PMID- 1881308 TI - Diffusion and perfusion in high resolution NMR imaging and microscopy. AB - Diffusion and perfusion phenomena under strong gradient fields (approximately 100 G/cm) are examined in high resolution nuclear magnetic resonance (NMR) imaging and microscopy, where diffusion-associated signal attenuation predominates over T1 and T2 relaxation decays. Image contrast based on the diffusion and microcirculation is discussed with experimental results obtained with a 7.0-T microscopy system. Ultimate resolution limit due to diffusion is investigated in high resolution NMR imaging and microscopy. PMID- 1881309 TI - Diffusion imaging using stimulated echoes. AB - The application of stimulated echo acquisition mode (STEAM) sequences for NMR imaging of diffusion is especially suited for spins with T1 much greater than T2 as, e.g., encountered in proton NMR studies of biological systems. Molecular self diffusion coefficients may be calculated from a set of diffusion-weighted images acquired with different gradient strengths. A variation of the diffusion time allows the determination of restricted and/or anisotropic diffusion in cellular systems ranging from plants to humans. Problems associated with the presence of unavoidable macroscopic motions in vivo are demonstrated in diffusion studies of human brain. Motion ghosting in diffusion-weighted images may be overcome by means of a high-speed STEAM sequence yielding single-shot images within subsecond acquisition times. PMID- 1881310 TI - Analytical solution and verification of diffusion effect in SSFP. AB - Assuming that the SSFP magnetization response maintains a steady state which is periodic in the presence of diffusion, we can solve for the diffusion effect in such sequences. Formulating a Fourier series decomposition solution to the Bloch Torrey equation and imposing the steady-state condition, analytical expressions describing the signal decay due to diffusion are developed. Magnetization responses for any system and sequence parameters can then be obtained. Also, sensitivity to b factor changes is quite different than standard diffusion measurement techniques. Assumptions made in the solution are verified via finite difference solutions and simulations of the Bloch-Torrey equation. PMID- 1881311 TI - Echo-planar imaging of diffusion and perfusion. AB - Use of the Stejskal-Tanner sequence for performing diffusion images in the human brain tends to be complicated by the presence of artifacts caused by voluntary or involuntary, sometimes pulsatile, motion. We describe the implementation of the technique of echo-planar diffusion imaging, which avoids these artifacts and allows reproducible quantitative values of the diffusion coefficient to be measured in vivo. The effects of perfusion are easily visible in a phantom containing a gel. The results for human brain show a significant "perfusion fraction" in grey matter, consistent with an extracellular, possibly microvascular, volume of about 10%. PMID- 1881312 TI - Magnetic resonance diffusion/perfusion phantom experiments. AB - Recently, several models for determining microcirculatory parameters using magnetic resonance imaging have been proposed. These include the intravoxel incoherent motion (IVIM) model, the intravoxel coherent motion (IVCM) model, and various tracer models. In order to evaluate these models before extension into physiological systems, phantom studies were used to assess model assumptions, measurement uncertainties, and sensitivity to changes in perfusion. Emphasis is placed on the IVIM model, but the techniques discussed could be extended to evaluation of other models as well. An overview of considerations in pulse sequence development, phantom design, and data interpretation is presented for a variety of phantoms ranging in complexity from stationary volumes of fluid and mechanically pumped phantoms to isolated animal kidneys and finally to an in vivo animal model. PMID- 1881313 TI - Effect of bulk tissue motion on quantitative perfusion and diffusion magnetic resonance imaging. AB - The effect of irreproducible bulk tissue motions upon quantification of tissue perfusion and diffusion was studied via computer simulation of random phase error in conventional phase-encoded perfusion/diffusion MRI. Simulations using acquisition parameters typical for human brain studies demonstrate that bulk motion irreproducibility of approximately 60 microns/s can produce phase instability on the order of 20 degrees which overwhelms estimates of perfusion fraction and produces significant errors in diffusion values. Bulk tissue motion control of the human brain via cardiac gating and substantial head restraint was studied by direct measurement of voxel phase stability. Phase instability of 10 degrees to 20 degrees was observed from right-to-left and anterior-to-posterior motions and significantly greater phase variability from superior-to-inferior motion. The spatial pattern of phase variability indicates the source is likely a mixture of cardiac pulsation and respiration. PMID- 1881314 TI - Applications of the intravoxel coherent motion technique to the central nervous system. AB - Phase difference images, obtained by comparing data from motion-sensitized and unsensitized spin-echo sequences, can be used to study intravoxel coherent motions. The resulting images, which have been routinely used to study fast flowing blood, may potentially yield information about perfused flows and bulk tissue motion. The likely limitations and potential of this technique applied to the central nervous system are reviewed with reference to parallel studies of intravoxel incoherent motion. PMID- 1881315 TI - Very slow flow imaging. AB - Two methods allowing imaging of very slow coherent flows are presented. The first method is based on the use of a radiofrequency field gradient. The second method is based on the use of gradients of the main field. Both methods include suppression of signal from stationary spins. A flow contour map is obtained which allows quantitative determination of velocity. The methods were proved to be efficient to image velocities as low as 10 microns.s-1. PMID- 1881316 TI - Studies of restricted diffusion in heterogeneous media containing variations in susceptibility. AB - Measurements of water self-diffusion in heterogeneous media by pulsed gradient spin-echo methods depend on the precise choice of experimental parameters. This variation may reflect the presence of restricted or anisotropic diffusion, or the presence of intrinsic magnetic field gradients. In experiments at 2.0 T, restricted diffusion effects have been demonstrated in freshly excised tissues with an effective barrier radius of order 10 microns. In samples with intrinsic susceptibility variations such as tissues or gels containing dispersions of iron oxide particles, the reduction of apparent diffusion coefficient with diffusion interval can be used to estimate the degree of heterogeneity of the magnetic field in the sample. The implications of these effects for diffusion-weighted MRI as well as their use to derive novel tissue parameters are discussed. PMID- 1881317 TI - Contrast agents and cerebral hemodynamics. AB - Contrast-enhanced magnetic resonance imaging of regional cerebral hemodynamics is discussed. Techniques for measuring cerebral blood volume (CBV) have been validated in animal models and have recently been applied to human studies. Factors affecting CBV measurement in pathologic tissue are addressed. Extension of these techniques to the measurement of cerebral blood flow is presented. PMID- 1881318 TI - Dynamic imaging of contrast enhancement in brain tumors. AB - Gadolinium-DTPA has been shown to be a good probe for demonstrating defects in the blood-brain barrier, but it has a rapid rate of elimination so that peak circulating levels are short-lived. In this study ultrafast echo-planar imaging has been used in combination with a bolus injection of gadolinium-DTPA to evaluate perfusion within brain tumors and to assess the degree of disruption of the blood-brain barrier. The temporal profile of enhancement may allow discrimination between different tumor types. PMID- 1881319 TI - The validation of freely diffusible tracer methods with NMR detection for measurement of blood flow. AB - While the general theory of measuring organ perfusion using exogenously administered freely diffusible tracers was originally formulated over 40 years ago, the application of NMR techniques for tracer detection is a recent development. A brief theoretical review and discussion of the literature validating the use of deuterium and fluorine as NMR-detectable tracers is provided. PMID- 1881321 TI - Diffusion-weighted MR imaging of extraaxial tumors. AB - The clinical usefulness of the application of spin-echo diffusion-weighted imaging in the evaluation of extraaxial cysts and epidermoid tumors is demonstrated in a series of 15 patients. Apparent diffusion coefficient (ADC) images based on intravoxel incoherent motion (IVIM) were obtained with a maximum gradient b value = 100 s/mm2. Lesion ADC was qualitatively compared to external phantoms. In all cases, epidermoid tumors revealed reduced ADC values similar to that of normal brain tissue. On the other hand, all cysts had ADC similar to the stationary water phantom. Lesion delineation was improved due to the replacement of normal pulsatile (very high ADC) cisternal CSF. Direct quantitative measurements of ADC using this technique may not be possible due to unavoidable motion artifact. PMID- 1881320 TI - Diffusion/perfusion MR imaging of acute cerebral ischemia. AB - In vivo echo-planar MR imaging was used to measure apparent diffusion coefficients (ADC) of cerebral tissues in a comprehensive noninvasive evaluation of early ischemic brain damage induced by occlusion of the middle cerebral artery (MCA) in a cat model of acute regional stroke. Within 10 min after arterial occlusion, ADC was significantly lower in tissues within the vascular territory of the occluded MCA than in normally perfused tissues in the contralateral hemisphere. Sequential echo-planar imaging was then used in conjunction with bolus injections of the magnetic susceptibility contrast agent, dysprosium DTPA BMA, to characterize the underlying cerebrovascular perfusion deficits. Normally perfused regions of brain were identified by a dose-dependent 35-70% loss of signal intensity within 6-8 s of contrast administration, whereas ischemic regions appeared relatively hyperintense. These data indicate that sequential diffusion/perfusion imaging may be useful in differentiating permanently damaged from reversibly ischemic brain tissue. PMID- 1881322 TI - Restricted and anisotropic displacement of water in healthy cat brain and in stroke studied by NMR diffusion imaging. AB - The occlusion of the middle cerebral artery in cat brain was used as an experimental stroke model to investigate the physical basis of the recently reported lowered diffusion constant of water in acute infarcted brain tissue (Moseley et al., Magn. Reson. Med. 14, 330, 1990). The original findings were confirmed in this study of 12 animals investigated with the diffusion-sensitized stimulated echo sequence. The following additional results were obtained: First, the onset of significant lowering of the diffusion constant in the stroke area varied significantly (up to 2.5 h depending on the animal). Second, the affected area is much more clearly outlined in diffusion-weighted images than in T2 weighted images, even in the period between 3 to 12 h following occlusion. Third, for diffusion times between 50 and 2000 ms. the diffusion constant of water is independent of diffusion time in healthy tissue, as well as in the stroke area. Fourth, the diffusion anisotropy is similar in healthy and in stroke area and remains similar regardless of the diffusion time used. PMID- 1881323 TI - Noninvasive temperature imaging using diffusion MRI. AB - Efficacy and safety considerations for cancer therapy with hyperthermia require accurate temperature measurements throughout the heated volume. We report the use of molecular diffusion, whose temperature dependence is well known. A dedicated hyperthermia applicator was built, combining a MRI gradient coil and a rf coil. Diffusion and derived temperature images were obtained with a 1 x 2 mm pixel size on a polyacrylamide gel phantom using a clinical 1.5-T whole body MRI system. Temperatures determined from these images using 1 cm2 regions of interest were found to be within 0.2 degrees C of those recorded from the thermocouples and fiber-optic probes placed inside the gel. PMID- 1881324 TI - The visibility of the 1H NMR signal of ethanol in the dog brain. AB - In vivo, high-resolution, volume-selected 1H NMR spectroscopy was used to monitor the concentration of ethanol in the dog brain following intravenous injection of ethanol. Equilibration of ethanol in the body water should result in approximately equivalent concentrations of ethanol in the blood and brain. However, the mean equilibrium brain ethanol concentration determined using N acetylaspartate as an internal standard was only 23 +/- 5% of the blood ethanol concentration. The disparity between blood and brain ethanol concentrations was attributed to underestimation of the ethanol concentration due to overlapping resonances with NAA and to T2 attenuation or possible nondetection of the 1H signal from ethanol bound at the surface of cell membranes and partitioned into the hydrophobic core of membrane lipids. PMID- 1881325 TI - Reduction of flow artifacts in NMR diffusion imaging using view-angle tilted line integral projection reconstruction. AB - Most of the diffusion imaging techniques employ strong diffusion gradient pulses of long duration in order to achieve appreciable signal attenuation through the diffusion effect. However, these strong and long gradient pulses make the resultant images extremely sensitive to the motion or flow of the object. Fourier imaging, with which most of the current NMR imaging is performed, is especially sensitive to the fluctuating flow and the images are usually obscured by severe flow artifacts smeared in the phase-encoding direction. In this paper, we have proposed a diffusion imaging technique which reduces the flow artifacts by use of the line-integral projection reconstruction (LPR) imaging method. Furthermore, the inhomogeneity artifacts expected to occur in LPR imaging have been corrected by application of the view-angle tilting technique. The pulse sequence of the view-angle tilted LPR diffusion imaging is designed in such a way that it works for both isotropic and anisotropic diffusion. Experimental results are presented along with the experimental procedures. PMID- 1881326 TI - MR angiography without subtraction. AB - A new NMR method for producing angiograms with strong suppression of the static spin signal and without the need for subtraction is described and demonstrated. A velocity-selective pulse sequence was implemented whereby the magnetization of all stationary spins is driven to the -z axis and is not detected, while maximizing the signal intensity of the moving spins. A theory of the method is presented and gives good agreement with experimental results obtained on a flow phantom. It is shown theoretically and experimentally that high-quality velocity independent angiograms of the head and neck can be obtained with strong suppression of static spin signal when TR approximately T1. The method can be extended to produce three-dimensional angiograms. PMID- 1881327 TI - Hepatic intracellular pH in vivo using F-quene 1 and 19F NMR spectroscopy. AB - Intracellular pH (pHi) has been determined in vivo in livers from anaesthetized rats using both 31P NMR and 19F NMR spectroscopy. In the 31P NMR study pHi, determined from the chemical shift of endogenous Pi, was found to be 7.26 +/- 0.02. In the 19F NMR study on a separate group of animals pHi was determined from the chemical shift of F-Quene 1 infused via the portal vein and found to be 7.18 +/- 0.01. In approximately half of the 19F NMR studies no 19F signal could be detected in the liver probably because of the two probes could be caused by different intra- or intercellular distributions or by unknown effects of F-Quene 1 on metabolism. PMID- 1881328 TI - Fast Fourier projection for MR angiography. AB - We have developed a technique called fast Fourier projection which rapidly produces projections through images and is particularly useful for generating MR angiograms. Based on the projection-slice theorem of Fourier transform theory, this method extracts planes from three-dimensional spatial frequency space and computes projections at arbitrary viewing angles by two-dimensional inverse Fourier transformation. Typical computation times are on the order of 1 s per projection. This performance makes possible interactive selection of optimal projection directions for visualizing the desired vasculature in single or stereo pair angiographic images and drastically reduces the time required to generate sequences of projections for display in movie loops compared to the conventional ray-casting approach. The method is easily implemented on off-line workstations or directly on MRI computer systems. PMID- 1881329 TI - Gadolinium-labeled liposomes containing various amphiphilic Gd-DTPA derivatives: targeted MRI contrast enhancement agents for the liver. AB - Unique paramagnetic liposomal contrast agents were synthesized and utilized for selective augmentation of T1 MR imaging of the livers of normal Balb/c mice. A series of amphipathic gadolinium complexes, which mimic phospholipids, was incorporated into the lamella of small unilamellar liposomes such that they become an integral part of its surface. The amphipathic complexing agents consisted of DTPA reagents in which two stearyl chains are attached via amide, ester, and thioester linkages. The in vitro stability and the in vivo lifetimes of the new amphipathic agents were dependent on the method used to attach the long-chain alkyl groups. PMID- 1881330 TI - 31P NMR spectroscopy of 9L cell line in culture: differential effects of high temperature on anchored cells and spheroids. AB - The differential effects of high temperature on 9L rat gliosarcoma cells cultured in two distinctive forms, namely, anchored monolayer cells and multicellular spheroids, were investigated using 31P nuclear magnetic resonance spectroscopy. The critical temperatures resulting in irreversible changes in cellular energetics were found to be significantly different: 45 degrees C for anchored cells and 43 degrees C for multicellular spheroids, respectively. Phosphomonoester levels in multicellular spheroids were found to be consistently higher than those in anchored monolayer cells regardless of the temperature to which they were exposed. The study demonstrates that tissue derived from a single cell line may exhibit different metabolic properties depending on its growth pattern. PMID- 1881331 TI - Localized 1H NMR spectroscopy in Canavan's disease: a report of two cases. AB - Two children with Canavan's Disease, an autosomal recessive leukodystrophy, were studied by localized 1H spectroscopy. The N-acetylaspartate (NAA) signal intensity was high relative to other metabolite signals, and the signal intensity from choline-containing compounds was low. These findings are discussed in relation to a possible role for NAA in normal myelination. PMID- 1881332 TI - A dual-frequency circularly polarizing whole-body MR antenna for 69/170 MHz. AB - The design concept of a dual-frequency whole-body MR antenna for circular polarization is presented. First, the principle of the capacitively shortened transmission line antenna, which is the basis of the design, is discussed. Emphasis is given to the antenna design at high frequencies. Two variants of possible antenna constructions are described and the RF efficiency is calculated for both frequencies. The antenna performance is discussed for the example of 69 and 170 MHz, the nuclear magnetic resonance frequencies of the nuclei 31P and 1H at 4 T. For 31P experiments, a whole-body antenna is useful only for transmitting and, thus, the antenna performance can be optimized for 1H. The design principle is not limited to two frequencies; however, the RF efficiency decreases with an increasing number of resonance frequencies. Results of a laboratory version and 1H images at 4 T are presented. PMID- 1881333 TI - On the use of a slice-selective 270 degrees self-refocusing Gaussian pulse for magnetic resonance imaging. PMID- 1881334 TI - On the use of a slice-selective 270 degrees self-refocusing Gaussian pulse for magnetic resonance imaging: comments on the note by D. M. Doddrell et al. PMID- 1881335 TI - Multiecho, spin-echo sequence to eliminate unwanted echoes. AB - Two types of artifacts--a mirror-reversed image about the phase-encode direction and a wave-like intensity variation across the image--may appear when using a conventional multiecho spin-echo sequence. We describe and demonstrate a new method, which eliminates such artifacts, using only one excitation per phase encoding step and without the need for spoiler gradients. PMID- 1881336 TI - Sequential 2D inflow venography: initial clinical observations. AB - Sequential 2D inflow NMR (SDI) venography was employed to define venous anatomy and pathology in five healthy subjects and five patients, mean age 48 +/- 7 years, with documented deep vein thrombosis. SDI images were graded independently by two observers on a scale of 1,2 nondiagnostic and 3,4 diagnostic categories. All iliac and femoropopliteal SDI venograms were diagnostic. In contrast, only one out of nine calf SDI venograms was diagnostic. SDI is a promising new method to assess the proximal peripheral venous system. Improved imaging strategy is needed to produce flow images of the calf veins. PMID- 1881337 TI - Longitudinal spin-order-based pulse sequence for lactate editing. AB - A new pulse sequence which edits proton spectra of lactate with full signal return and gives good suppression of water and fat signals is described. This sequence exploits longitudinal spin-order from lactate to edit lactate from fat. Experimental results from phantoms and excised pig heart are presented. PMID- 1881338 TI - A magnetization transfer preparation scheme for snapshot FLASH imaging. AB - A rapid method of generating images whose contrast is dependent on the exchange of magnetization between the free and restricted proton pools is presented. The contrast obtained is similar to that obtained from T2-weighted spin-echo images. The rapid nature of the sequence means that the RF power deposition problems encountered when using magnetization transfer in conjunction with conventional imaging sequences are avoided. PMID- 1881339 TI - Spectroscopic imaging using variable angle excitation from adiabatic plane rotation pulses. AB - The technique of chemical-shift (spectroscopic) imaging has been implemented using a variable angle adiabatic plane-rotation pulse for small angle excitation over the entire sensitive volume of a surface coil. Optimum signal-to-noise ratio per unit time is obtained in applications where the pulse repetition rate is fast relative to 1/5 T1. PMID- 1881340 TI - Leadership in mental retardation. PMID- 1881341 TI - Consent screening interview for community residential placement: report on the initial pilot study data. AB - A preliminary investigation of the reliability and validity of the Consent Screening Interview is described. The instrument was designed to assess the ability of adults with developmental disabilities to give direct consent for community residential placement. Our three objectives were to: (a) establish content and construct validity through administration and expert evaluation, (b) establish preliminary baseline scoring criteria; and (c) make any needed revisions based on expert appraisal and administration of the instrument to a target population. Initial results indicated that this instrument differentiated between those subjects considered competent to give consent and those whose ability to give consent was questionable. PMID- 1881342 TI - Burnout among staff members at community residential facilities for persons with mental retardation. AB - The Maslach Burnout Inventory was used to measure burnout among 125 staff members working in community residential facilities for persons with mental retardation in North Dakota. Results showed that a moderate degree of burnout was present for direct-care and supervisory staff members in each of the three subscales of the inventory. In addition, supervisory staff members showed significantly more burnout on the Emotional Exhaustion subscale and significantly less on the Personal Accomplishment subscale than did direct-care staff members. Results were discussed in light of previous findings. PMID- 1881343 TI - Efficiency considerations in delivering special education services to persons with severe mental retardation. AB - The basic question addressed in this paper is whether formal benefit-cost and effectiveness-cost analyses might allow us to determine whether the outcomes of particular special education services are being offered in their most efficient manner. In attempting to answer this question, we focused upon measuring as many of the cost and outcomes as possible (in both monetary and other terms) from two specialized schools serving youth with severe mental retardation. We examined a number of alternative assumptions for illustrating some of the problematic issues in the use of such evaluation techniques. PMID- 1881344 TI - Psychotropic medication efficacy graphs: an application of applied behavior analysis. AB - Boswell Center Psychotropic Medication Efficacy Graphs were developed to monitor the longitudinal effects of psychotropic medication on individuals with mental retardation. Levels of maladaptive and prosocial behaviors, medication side effects, and psychotropic medication were considered simultaneously via the graphing system. The system provides data-based feedback to prescribing physicians and reduces reliance on anecdotal recollections. PMID- 1881345 TI - Validation of the parenting style survey for parents of children with mental retardation. AB - A validation study was performed in order to assess the content, construct, and criterion-related validities of the Parenting Style Survey, an instrument assessing parental behavior in families with a child who has mental retardation. Subjects were the primary careproviders of 29 individuals with moderate mental retardation. Data corroborating the validity of the Parenting Style Survey were derived from home visits, individuals experienced in developmental psychology, careproviders for individuals with mental retardation, and the Family Environment Scale (Moos, 1974). The Parenting Style Survey is a reliable and valid measure of parenting behaviors for individuals who have a child with mental retardation living at home. PMID- 1881346 TI - Evaluation of environmental support in group homes for persons with mental retardation. AB - Types of environmental support provided to adults with mental retardation in group homes after transfer from a large state institution were compared. Substantial differences in the functioning of the group homes were found even though the service structure was held constant. Community adjustment was compared for matched groups of residents of the group homes. Differences in community adjustment occurred for residents in group homes with significantly different functional features. The findings indicate that resident outcome was generated by the interaction of several factors in combination. Both structural and functional features of facilities must be considered in any evaluation of the effectiveness of community programs. PMID- 1881347 TI - Molecular dosimetry of sister chromatid exchange induction in 9L cells treated with 6-thioguanine. AB - The induction of sister chromatid exchanges (SCE) in 9L cells treated with 6 thioguanine (6-TG) has been investigated. A 24 h treatment with 0.2 microM 6-TG induced approximately 28 SCE/metaphase. The dose-response curve was linear at doses below 0.2 microM and had a slope of 139 SCE/metaphase/microM 6-TG. At concentrations of 0.023 to 1 microM, incorporation of 6-TG in DNA was linear with dose. The slope of the dose-response curve was 4135 mumol 6-TG/mol DNA/microM 6 TG. Comparison of these results with those obtained in our previous studies of the monofunctional alkylating agent ethylnitrosourea and the bifunctional alkylating agent 3-(4-amino-2-methyl-5-pyrimidinyl)methyl-1-(2-chloroethyl)-1 nitrosourea suggest that to accurately estimate the effectiveness of particular DNA modifications at inducing SCE, the extent of formation of these DNA modifications must be known. PMID- 1881348 TI - Mutagenic contaminants in synthetic peptides obtained by an azide coupling. AB - Hormone-like peptides are, almost by definition, not mutagenic. It was, therefore, unusual to find that some batches of peptides synthesized by azide coupling were mutagenic in the Ames test. One of these peptides, eledoisin, showed mutagenic activity particularly in Salmonella typhimurium TA 1535 without metabolic activation. This activity was independent of the peptide purity determined by HPLC and a dose response relationship was observed at concentrations over the solubility limit of the peptide in the assay medium. We therefore suggested that the mutagenic effect might be due to the presence of chemically undetectable, water-soluble impurities, which could be removed by counter-current distribution. If, however, the same final coupling was carried out by the mixed anhydride procedure, no mutagenic activity was observed. Consequently, we considered that the mutagenicity detected was due to traces of hydrazoic acid salts arising during azide formation in the coupling step. In fact only the product of the coupling reaction between the pivotal intermediates was mutagenic. PMID- 1881349 TI - Cytogenetic study in workers occupationally exposed to mercury fulminate. AB - This study was conducted to evaluate the cytogenetic effects in male workers exposed to mercury fulminate. A total of 29 male workers and 29 age- and sex matched controls were examined. The mean mercury level in urine from the exposed workers was 123.2 +/- 54.1 micrograms/l compared with 39.2 +/- 11.1 micrograms/l in the control group. The difference was statistically significant (P less than 0.001). Metaphase chromosomes were studied. Micronucleated peripheral blood lymphocytes were also analyzed in cytochalasin B blocked binucleated lymphocytes. The percentage of metaphases with chromosomal aberrations was significantly higher (P less than 0.001) in the exposed group (6.1 +/- 2.3) compared to the control group (2.8 +/- 0.7). The chromosomal aberrations detected were in the form of gaps, breaks and fragments. A significant increase in the incidence of micronucleated lymphocytes was found among the exposed group (7.1 +/- 4.2) compared to the control group (5.4 +/- 2.2) (P less than 0.01). The detected chromosomal damage correlated neither with the duration of exposure nor with the urinary mercury level. PMID- 1881350 TI - Micronucleus morphology as a means to distinguish aneugens and clastogens in the mouse bone marrow micronucleus assay. AB - Detailed dose-response data for two reference aneugens, vincristine and nocodazole, have been derived for the mouse bone marrow micronucleus assay. Positive data have also been described for six other micronucleus-inducing agents: cyclophosphamide; aniline; urethane; 1,2-dimethylhydrazine; 7,12 dimethylbenzanthracene and procarbazine. Micronuclei (MN) were classified according to the morphological criteria listed by Yamamoto and Kikuchi, i.e. normal, double, multiple, ring, crescent and large. Aniline and control slides exhibited low incidences of aberrant MN (less than 3%). The remaining seven chemicals gave incidences of aberrant MN that varied from 3 to 25%. Only the aneugens vincristine and nocodazole, and the possible aneugen urethane, gave both crescent shaped and large MN (greater than 0.25 cell diameter). It is therefore concluded that only these last two classes of aberrant MN can be taken as indicative of aneugenic activity. Vincristine and nocodazole gave the highest incidences of aberrant MN and these were shown to be strongly dose-related in the case of vincristine. PMID- 1881351 TI - An association between mutagenicity of the Ara test of Salmonella typhimurium and carcinogenicity in rodents for 16 halogenated aliphatic hydrocarbons. AB - Sixteen halogenated aliphatic hydrocarbons were assayed for genotoxicity using the Ara mutagenicity assay with Salmonella typhimurium. Seven substances (1,2 dibromo-3-chloropropane, 1,2-dibromoethane, 1,2-dichloroethane, vinyl bromide, hexachloro-1,3-butadiene, iodoform and vinilydene chloride) were mutagenic at non lethal doses. Comparatively, nine compounds (chloroform, carbon tetrachloride, 1,1,1-trichloroethane, 1,1,2-trichloroethane, tetrachloroethylene, trichloroethylene, 1,1,1,2-tetrachloroethane, 1,1,2,2-tetrachloroethane and hexachloroethane) were non-mutagenic after being assayed both in the presence and absence of metabolic activation with a rat liver microsomal fraction (S9). All negative compounds (except hexachloroethane) gave a lethal response, which could be an indication that bacteria were adequately exposed. The concordance between mutagenicity in the Ara test and carcinogenicity in rodents for this group of halogenated hydrocarbons was (31%) significantly lower than the concordance (72%) previously found in the Ara test with respect to a wider range of chemical classes. This result is in agreement with data reported for other genotoxicity assays. The presence of non-genotoxic carcinogens versus genotoxic non carcinogens is discussed as a possible explanation. Five positive compounds (1,2 dibromo-3-chloropropane, 1,2-dibromoethane, 1,2-dichloroethane, vinyl bromide and hexachloro-1,3-butadiene) were analyzed for a quantitative relationship between carcinogenic potency in rats and the potency of response in the Ara mutagenicity test. This was possible because the Ara test, for volatile compounds (such as vinyl bromide), did not require the use of special vaporization techniques, which are difficult to evaluate quantitatively for mutagenic activity. A highly significant correlation was found between the mutagenic efficiencies of the five compounds in the Ara test and their carcinogenic potencies in rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881353 TI - [Analysis of early, delayed phase and late cutaneous reactions to ten groups of antigens in 581 patients with allergic rhinitis]. AB - Immediate, late phase and delayed skin reactions against ten group of allergens were investigated in 581 patients with allergic rhinitis. The wheal and flare reaction were characteristic for type 1 IgE mediated hypersensitivity reaction in human skin. This reaction develops rapidly after injection of antigen, peaks in 10-30 minutes, and then subsides within a few hours. However, careful observation for longer periods has shown that in many instances a late inflammatory response also appears at the same site and is quite different in appearance from the initial reaction. In this study, we have investigated immediate, late phase also delayed phase skin reactivity incidence of the allergic rhinitis patients. PMID- 1881352 TI - Induction of mutations at the thymidine kinase locus in CHO cells by restriction endonucleases. AB - Induced mutation frequencies were measured at the tk locus (encoding for the enzyme thymidine kinase) following treatment of Chinese hamster ovary cells (CHO KI) with two restriction endonucleases (REs), PvuII and EcoRI, which generate 'blunt-ended' and 'cohesive-ended' DNA double-strand breaks (dsb), respectively. Electroporation was used to introduce these enzymes into the cells. Restriction endonucleases generating blunt-ended dsb have been shown to mimic the action of ionising radiation in causing chromosome aberrations, cell killing, mutations and oncogenic transformation. Here we show that the tk locus, PvuII induced an approximately 11-fold higher mutation frequency than EcoRI at the same enzyme concentrations. There are four PvuII and six EcoRI restriction sites in the Chinese hamster thymidine kinase gene. Hence the higher mutation induction by PvuII, despite the lower number of restriction sites than EcoRI in the tk gene, suggests that blunt-ended dsb represent more effective and critical mutagenic DNA lesions than the cohesive-ended type. In this respect, our results are similar to those we obtained previously for chromosomal aberrations and for cell killing. Results from the present study suggest that mutations could arise from unrepaired or misrepaired dsb possibly via induction of chromosomal deletions or stable exchanges between chromosomes. PMID- 1881354 TI - [Hypersensitivity (allergy) and infection]. AB - In this subject, we would attempt to discuss some specific and non-specific mechanisms involved in immunity as well as hypersensitivity reactions against to infectious agents. Figure 1 presents a simplification of the response of allergic patient to microorganisms. Immunity, hypersensitivity and unresponsiveness to different antigens of the same infectious agents can occur simultaneously. For example, a patient who is sensitized and partially protected to toxins and other antigenic components of an infectious agents can be allergic to harmless components of the same organism. Sufficient exposure to the infectious agent may cause an allergic as well as an infectious disease. An allergic component of an infectious disease is suspected when the symptoms are unusually severe, protracted or occur in a known allergic patient. Modification of the hypersensitivity reactions becomes an important part of the treatment of the infection. PMID- 1881355 TI - [The effects of ciprofloxacin on intestinal flora and Paneth cells]. AB - The effects of ciprofloxacin were investigated on colonic microbial flora and Paneth cells in eight healthy albino rabbits following a 10 mg intravenous dose. Two rabbits were used as control group. Aerobic fecal cultures were negative on rabbits of experiment. Vacuolisation and reduction of eosinophilic fields were seen in Paneth cells by light microscopic examination. PMID- 1881356 TI - [In vitro sensitivity of gram-negative bacteria isolated from urinary tract infections to various antibiotics]. AB - This study was done on the outpatients and hospitalized patients who were suffering from urinary tract infections in Turkiye Yuksek Ihtisas Hospital. 500 positive cultures were evaluated. E. coli was the predominant organism and it is followed by Klebsiella and Coliform bacteria. The sensitivity of the isolated bacteria were tested against various antibiotic discs using disc diffusion method. The sensitivity of the bacteria to the used antibiotics were as follows: Ceftazidime 96%, ofloxacin 95.6%, piperacillin 56.4%, amoxycillin + clavulanic acid 81.2%, amikacin 82.2%. PMID- 1881357 TI - [Detection of influenza B virus antibodies in different age groups using hemagglutination inhibition tests]. AB - Antibody levels against influenza B virus were investigated by using hemagglutination-inhibition (HA-I) tests in 402 sera obtained from different age groups. Hemagglutination antigens were obtained by production of influenza B virus (B/Singapur/LLC 6201) in trypsinized Madin Darby Bovine Kidney (MDBK) cell cultured and they were used in tests. In 355 out of 402 sera (88.3%) antibodies against influenza B virus were detected at titers varying between 1/20 and 1/1280. However in 47 sera (11.7%) no antibodies were detected at 1/20 titer. High titers of antibody (1/640-1/1280) were not detected in none of the sera obtained from an age group between 1 and 14. However high titer antibodies were detected in 15.6% of the sera from an age group between 26 and 35, in the 17.3% of the sera from a group above 50 years of age. Our findings suggest that the increase in the rates of seropositivity against influenza B virus depends on getting older and, that the infections by this virus may be widely seen in our country. PMID- 1881358 TI - [Incidence of rubella IgG antibodies in young girls]. AB - Rubella IgG antibodies were searched in 222 sera from female students of Selcuk University School of Medicine and from Institute of Higher Education for Nurses aged between 18-20 years. Of these 31 (13.96%) were found seronegative by ELISA. We discussed the risk of infection of these young girls. PMID- 1881359 TI - [Serological investigation of HIV infections, HBsAg and syphilis in prostitutes in Elazig]. AB - It is well known that the infections of AIDS, serum hepatitis and syphilis were transmitted by sexual contact. The sera of 66 prostitutes were investigated for determination of anti-HIV by ELISA, HBsAg by IHA and antibodies to syphilis by TPH methods in area of Elazig. The anti-HIV antibodies could not be detected in prostitutes, but HBsAg was positive in 13 (19.7%) and antibodies to syphilis was positive in 6 (9.1%) of total. PMID- 1881361 TI - [The antifungal effects of tioconazole aerosol form]. AB - In this study antifungal effects of tioconazole which is prepared in aerosol forms were investigated. For this purpose, the formulations which have and have not active material were sprayed on petri dishes inoculated with Candida albicans and Aspergillus niger. Because of non growth in dishes with formulations containing active material, formulations with active material were sprayed on to the pregrowth Candida albicans and Aspergillus niger in order to detect if the effect is fungicide or not. At the end of application time, the samples taken from these dishes were inoculated by the direct way. The lack of growth had confirmed the realization of the formulations with fungicide effects. PMID- 1881360 TI - [Intestinal parasites in primary schools of different socioeconomic status and environmental conditions]. AB - Two hundred ninety-four stool sample obtained from primary schools of different social status and environmental conditions were examined for intestinal parasite. The age range was between seven and 13 years, 43% of the patients were females and 57% of the patients were males. In our study it has been observed that the parasite incidence was 29.3%. The predominant parasite was Giardia intestinalis (15.7%). Enterobius vermicularis (10.5%) and Ascaris lumbricoides (2.3%) have been followed respectively. There were three different parasites in the primary school of good social status and environmental conditions. In the contrary in the village school, there were five different parasites. In the conclusion parasite incidence was high in our region. In primary schools of different conditions there were no difference Giardia intestinalis but there were marked difference in the other parasites. PMID- 1881362 TI - [The role of Candida albicans in denture stomatitis]. AB - Denture stomatitis is a clinical inflammatory picture that is seen at oral mucosa of the upper chin of patients who use removable dentures. There are various reasons of denture stomatitis. In order to detect the presence rate of C. albicans on lesions as the most important factor and the factors which effect this situation, 41 patients (31 with denture stomatitis and 10 as controls) were chosen. The smears obtained from the hard palate of the patients were microbiologically investigated. C. albicans was found to be the causative agent in 35.4% of the cultures which have shown growth. The relationship of sex, age and the period of denture usage was investigated in these cases. PMID- 1881363 TI - [The effect of magnetic retainers used in dental prostheses on the pathogenic microorganisms in the oral flora]. AB - Patents for magnetic denture retainers in dental prosthesis, have issued since 1930, but recent developments rekindled interest. There have been many studies reporting the effects of magnetic fields on humans, animals, insects, tissue cultures, micro-organisms and enzymes. In some of these reports, damaging tissue effects were observed. In our study, the effect of these magnets to the growth of pathogen microorganisms found in oral flora were investigated with 2 different microbiological methods. In either of these methods, it was determined that the magnetic field didn't affect the colonization of bacteria. PMID- 1881364 TI - [Transformation studies of E. coli strain JM109 with the pUC19 vector]. PMID- 1881365 TI - [The mutagenic effects of sodium nitrite and monosodium glutamate used as food additives demonstrated by the Salmonella microsome test system]. AB - In this study, the mutagenicity of sodium nitrite (an antimicrobial agent) and monosodium glutamate (a flavoring agent), which are widely used as food additives, have been evaluated. They were tested for mutagenicity in the Salmonella/microsome test system by employing plate-incorporation test in the absence and presence of rat-liver fraction, S 9. No mutagenic activity was seen for monosodium glutamate in the Salmonella/microsome test system by using the tester strains Salmonella typhimurium TA98, TA100, TA1535 and TA1538. Sodium nitrite was found mutagenic on S. typhimurium TA1535, whereas it was found weakly mutagenic on S. typhimurium TA100, in the presence and absence of rat-liver fraction, S 9. PMID- 1881366 TI - T lymphocyte-stimulating microbial toxins as "superantigens". AB - Infectious pathogens generally have to cope with the host's adaptive immune system, i.e., T and B lymphocytes. Common evasion mechanisms in this complex interaction are antigenic variations, the escape to immunologically priviledged sites or the use of immunosuppressive mechanisms. Many bacteria and other microorganisms eleborate soluble factors or toxins that act suppressively on cells of the immune system, such as pore-forming molecules or proteins that interfere with the function of G proteins. Gram-positive cocci and a mycoplasma have developed an extremely potent mechanism of T cell stimulation by closely mimicking recognition of specific antigen. From the functional similarity to antigen recognition and the multiclonal activation of T cells the designation "superantigens" has been suggested for these molecules. PMID- 1881367 TI - High risk of developing toxoplasmic encephalitis in AIDS patients seropositive to Toxoplasma gondii. AB - We studied 41 AIDS patients in the Austrian Tyrol with respect to toxoplasma antibody titers and the presence of CNS toxoplasmosis. In no patient had primary Pneumocystis carinii pneumonia (PcP) prophylaxis with either trimethoprim/sulfamethoxazole or pyrimethamine/sulfadoxine been applied; the degree to which CNS toxoplasmosis is influenced by this kind of PcP chemoprophylaxis, widely used elsewhere, is still unclear. In this study 47.4% of toxoplasma-seropositive patients developed CNS toxoplasmosis, compared to the previously estimated risk of 12%-28% for developing CNS involvement in such patients. In view of the high risk of toxoplasma-seropositive patients with AIDS, increased efforts in developing a well-tolerated chemoprophylaxis to combat CNS toxoplasmosis are required. PMID- 1881368 TI - Periodontal regeneration procedures may induce colonization by glycocalyx producing bacteria. AB - Sixteen patients that underwent periodontal regeneration procedures by implantation of Goretex membranes were studied to evaluate the microbiota that colonized membranes. The microbiological follow-up showed that colonization was principally due to opportunist gram-negative glycocalyx-producing bacteria. The comparison of the microbial flora of treated and untreated sites showed the influence of surface characteristics on the quality of the resident microbiota. These findings suggest the necessity for developing efficient prohylactic protocols for these cases. PMID- 1881369 TI - Carbohydrate patterns, cellular lipoquinones, fatty acids and phospholipids of the genus Pasteurella sensu stricto. AB - The carbohydrate patterns, isoprenoid quinones, fatty acids and phospholipids of the species of the genus Pasteurella sensu stricto were investigated to evaluate their taxonomic significance and their applicability for the identification of these bacteria. Forty-six representative strains of the 11 species of Pasteurella were examined. The data obtained indicated that the carbohydrate patters are species or subspecies specific and may, therefore, become an important and useful diagnostic tool. Fatty acids and phospholipids showed a feature characteristic of the members of the genus and the isoprenoid quinones exhibited a mostly genus specific feature with remarkable quantitative differences. PMID- 1881371 TI - Midwifery education--international. PMID- 1881370 TI - Objective quantitation of serum antibody titres against Enterobacteriaceae using indirect immunofluorescence, read by videocamera and image processing system. AB - A new way of measuring indirect immunofluorescence (IIF) of microscopic bacterial slide preparations by videocamera and an image processing system is presented. This method is compared with the conventional method of reading the slides by eye. The advantages of this new approach are objective reading, greater accuracy and easier performance. We have applied the method to measure serum antibody titres against endogenous Enterobacteriaceae. The method offers the opportunity to combine IIF with automatic morphological analysis, thereby maximally exploiting the possibilities of the immunofluorescence technique. PMID- 1881372 TI - Assessing comprehensive nursing performance: the objective structured clinical assessment (OSCA). Part 2--Report of the evaluation project. AB - Part 1 of this paper described the development of an assessment strategy used to measure the clinical performance of student nurses undertaking preparation for practice within the tertiary education sector. The challenge of developing an appropriate technique in assessment to accommodate a comprehensive nursing register was described. Features of the design and implementation were also provided. Part 2 describes an evaluation project developed by the staff and supported by a research grant from the New South Wales (NSW) Nurses Registration Board. The aim of the study was to determine the validity and reliability of the Objective Structured Clinical Assessment (OSCA) technique. The research design incorporated the use of triangulated data: student questionnaires, judgments made by a panel of experts and an analysis of the statistical correlation between the students' results in the OSCA and results in other areas of assessment. PMID- 1881373 TI - Problems of competence-based nurse education. AB - The system of nurse education in the UK is undergoing a radical shake-up. Many new courses are being designed and implemented along the lines of the Project 2000 framework. New curricula and course structures are required to meet the changing role of the nurse of the future. Many curriculum design teams are adopting a competence-based model of curriculum to meet these needs. This approach is receiving central encouragement (UKCC 1986). In this paper it is argued that this strategy is faulty and ill-conceived; the inherent difficulties of the competence-based model of curriculum design are highlighted. These issues are of fundamental concern to nurse educators and students in the UK. PMID- 1881374 TI - The support, supervision and instruction of nurse learners in clinical areas: a literature review. AB - This paper reviews recent work on the support, supervision and instruction of nurse learners in clinical areas. Work published in Britain and North America is divided into five sections: ward learning environment; quantity of supervision and teaching; effectiveness of clinical teachers; ward teachers' perceptions of their role and mentorship. The findings can be generalised within their country of origin, but do not necessarily translate freely across the Atlantic in view of the different systems of training. More research needs to be carried out into the mentorship of nurse learners in Britain in view of its increasingly wide use, especially with the advent of Project 2000 and the implications of supernumerary status for learners. PMID- 1881375 TI - Testing a model for counsellor training in three public health care organisations. AB - The article describes a training programme arranged for 26 specially qualified nurses who were to be placed in the role of nurse counsellors. The programme was tested over a period of 2 years in three public health care organisations: a central university hospital, a regional hospital and a community health centre. The aims were to develop a basic model for counsellor training and to test the model in practice; and more specifically, to evaluate the relevance of the theoretical instruction, practical exercises, and reading assignments included in the programme. Finally, on the basis of self-evaluations by the nurses involved, the aim was to find out how far the objectives set for the practical counselling by the nurses themselves were realised. The data were collected by means of a semi-structured questionnaire after the completion of the training course, and analysed using the method of content analysis. Percentage and frequency distributions were used for purposes of statistical description. The small sample size and the differences in the nature and goals of the health care organisations involved mean that there are important restrictions to the generality of these results. Nevertheless they give important clues for the further development of counsellor training schemes. PMID- 1881376 TI - Andragogy as a didactic perspective in the attitudes of nurse instructors in Finland. AB - In this article the didactic perspectives of nurse instructors (NIs) is examined with the help of andragogy defined by the concepts of self-directed learning, learning as a process and lifelong learning. The results of a pilot study of ongoing research on the educational perspective of NIs, are used as examples to discuss how far NIs have accepted the features of andragogy as their didactic perspective both in their public stance and in their actions as described by NIs themselves. PMID- 1881377 TI - Using critical learning incidents in nurse education. AB - This paper describes an attempt to provide a learning environment conducive to the development of conceptual skills in critical exploration and problem solving. This is achieved by using a method of reflecting on and about critical incidents encountered by student nurses during their nursing practice. It is argued that students need help in making links between theory and practice and the article relates how this may be achieved in workshops using mainly experiential techniques. The authors conclude that the use of such a strategy can make a valuable contribution to nurse education, enabling students to look at situations from multiple perspectives and heightening awareness of the complex skills involved in nursing. PMID- 1881378 TI - The ideal and the real: some thoughts on theoretical developments in British nursing. AB - Two types of nursing theory are described: the realistic, whose purpose is to account for the complex reality of nursing; and the idealistic, whose purpose is to describe an idealized world of nursing as it 'ought to be'. It is argued that British nurses have overemphasized the importance of idealistic theory, and that this has retarded the development of our understanding of the real world of nursing. I recommend that the hermeneutical approach, as described by Gadamer (1989) might provide a base from which the balance might be redressed. PMID- 1881379 TI - Post-registration degrees in nursing: a time for evaluation. AB - There is a steadily growing number of post-registration degrees for registered nurses being offered by universities and polytechnics. Despite this fact, there is little published research-based literature which investigates the career paths and plans of these graduates and the value and function of this type of degree course. This paper reviews the literature relating to post-registration degrees in nursing and discusses the reasons registered nurses may decide to undertake a post-registration degree, the possible benefits of studying for and attaining a post-registration degree and highlights the present position of master's degrees in nursing. Reasons are suggested as to why a comprehensive evaluation of post registration degree courses in nursing is required. PMID- 1881380 TI - Self-study programmes and nursing education. AB - This article gives an account of the use of 'self-study programmes' (SSPs) in a registered mental nurse curriculum. The account spans a period of over 3 years. It describes the development and implementation of two SSPs in the author's school and the generally favourable outcomes that were found to be associated with them. The perceived virtues of the self-study approach are described and, in conclusion, it is recommended that the approach be more widely used throughout nurse education generally. PMID- 1881381 TI - A constructivist approach to concept attainment. AB - A teaching strategy for concept attainment based upon a constructivist model is described and evaluated. The constructivist model is outlined, which suggests that students must construct their own knowledge, using their existing knowledge to do so. Transmission methods of teaching run the risk of concepts being altered to fit students' existing conceptions. A constructivist strategy for concept learning is exemplified drawing on the transcript of an experimental session conducted with a peer group of student teachers studying for the Certificate in Education. PMID- 1881382 TI - St. Louis encephalitis outbreak--Arkansas, 1991. AB - On August 2, 1991, a neurologist in Pine Bluff (Jefferson County) in central Arkansas notified the Arkansas Department of Health of two patients hospitalized with St. Louis encephalitis (SLE). A hospital chart review and heightened surveillance (i.e., notification of physicians and hospital infection-control coordinators in Jefferson and surrounding counties) subsequently identified 24 confirmed or probable cases of SLE. This report summarizes the findings of the ongoing outbreak investigation. PMID- 1881383 TI - Participation of high school students in school physical education--United States, 1990. AB - Regular physical activity increases a person's ability to perform daily activities with greater vigor and may reduce the risk for specific health problems, including coronary heart disease (1), hypertension (2), noninsulin dependent diabetes mellitus (3), colon cancer (4), and depression (5), as well as lower all-cause death rates (6). In addition to extracurricular activities (e.g., sports and recreational organizations), high school physical education (PE) classes provide an opportunity to ensure a minimal, regular amount of desirable physical activity and help establish physical activity patterns that may extend into adulthood. This report examines the prevalence of self-reported enrollment, attendance, and participation in PE classes by students in grades 9-12. PMID- 1881384 TI - Tobacco use among high school students--United States, 1990. AB - Tobacco use is the single most preventable cause of death in the United States. Approximately half of smokers start smoking regularly before 18 years of age; however, among recent birth cohorts, age of smoking initiation has declined, especially among females. Data on tobacco use among adolescents help identify high-risk populations, design tobacco-prevention programs for these populations, and evaluate the effectiveness of broad efforts to prevent tobacco use among youth. This report examines the prevalence of self-reported current tobacco use and frequent cigarette smoking among U.S. students in grades 9-12 during 1990. PMID- 1881385 TI - State tobacco prevention and control activities: Results of the 1989-1990 Association of State and Territorial Health Officials (ASTHO) survey final report. AB - In October 1989, the Association of State and Territorial Health Officials (ASTHO) conducted a survey of state health department personnel regarding programs, policies, and public health systems that stress the prevention and control of the use of tobacco. This survey provided detailed data associated with state tobacco-use control programs and their essential components (e.g., budgets, planning, coalitions, surveillance systems, smoking cessation programs, educational activities, legislative actions, and health department policies). States vary widely in the strength and coverage of their programs for preventing and controlling tobacco use. The ASTHO survey data may be used to help plan and evaluate state health department programs as part of an effort to prevent chronic diseases related to tobacco use. Outcomes of state activities may be evaluated through surveys such as CDC's Behavioral Risk Factor Surveillance System (BRFSS) and the Current Population Survey (CPS) of the Bureau of the Census. Future surveys of state activities for controlling the use of tobacco may be included in the evaluation of the upcoming (1993) American Stop Smoking Intervention Study (ASSIST), which is cosponsored by the National Cancer Institute and the American Cancer Society. PMID- 1881386 TI - Methionyl aminopeptidase from rat liver: distribution of the membrane-bound subcellular enzyme. AB - The selective distribution of methionyl aminopeptidase (MAP) among rat liver mitochondria (heavy and light) and microsomes is reported. Several properties of MAP from the three subcellular fractions showed that the enzyme is a typical aminopeptidase able to remove N-terminal methionine from oligopeptides and methionyl-2-naphthylamide but not from Met-Ala-Ser. MAP is a membrane-bound enzyme sensitive to SH-group oxidants and inhibitable by L-methionine but not by usual arylaminopeptidase inhibitors. It is suggested that, MAP may play an important role during protein synthesis in rat liver. PMID- 1881389 TI - [Conformational aspects of glycosylation]. AB - The stereochemical conditions of the enzymatic process of carbohydrate chain addition to the amino acid sequence are reviewed. A particular attention is given to the process of N-glycosylation, which was studied by the method of theoretical conformational analysis. PMID- 1881387 TI - Evidence that specific high mannose structures directly regulate multiple cellular activities. AB - Previous studies have demonstrated that much of the immunomodulatory activity of the glycoprotein uromodulin can be attributed to attached oligosaccharides. Structural studies of isolated and purified saccharides derived from uromodulin suggest that the structure Man6GlcNAc2-asn can inhibit in vitro assays of antigen driven T cell proliferation. Based on these observations, we isolated a series of high mannose glycopeptides from a variety of natural sources and tested them for biological activity in a number of assays. We found that purified mannose rich glycopeptides are able to activate the hexose monophosphate (HMP) shunt, induce prostaglandin synthesis, and directly stimulate IL-1 synthesis. These in vitro effects appear to have in vivo counterparts. Thus in a species-restricted fashion, high mannose compounds are able to directly activate a delayed mononuclear cell infiltrate after intradermal injection. Our data suggest that specific mannose oligosaccharides may activate as well as inhibit cellular immune responses at several different levels. These findings support the hypothesis that specific saccharide structures could participate in the physiologic regulation of the immune response. PMID- 1881388 TI - Effects of different rates of cardiac pacing on rat myocardial energy status. AB - The energy status of mammalian cells is a finely regulated phenomenon. This is especially true in cardiac muscle cells in which energy requirements are high and the system must provide rapid turnover of the adenine nucleotides and instant response to changes in energetic demands. We have examined the acute response of the rat myocardium to ventricular pacing up to 2.5 times the resting heart rate. The purpose of this study was to determine at what level of pacing the normal energy status could be maintained and at what point it was compromised. Myocardial energy charge (EC = (ATP + 0.5 ADP)/(ATP + ADP + AMP] was maintained at 1, 1.5 and 2 times the resting heart rate but declined significantly at 2.5 times. In contrast, phosphorylation potential (PP = ATP/ADPf x Pi) was drastically altered in hearts paced at 1.5, 2 and 2.5 times the resting rate. Tissue lactate increased and glycogen decreased in a linear fashion as pacing rate increased, indicating that the metabolic challenge was proportional to the pacing rate. EC seems to reflect the overall status of the cell and its ability to maintain a dynamic equilibrium. PP may reflect the immediate and necessary driving force for mitochondrial respiration in times of increased demand. These data suggest that the myocardium may meet the increased energy demands of acute ventricular pacing by shifting the molar ratio of ATP to ADP times Pi in favour of driving phosphorylation. PMID- 1881390 TI - [Oligo- and polynucleotide probes. A molecular hybridization method]. AB - In this review the main principles and possibilities of a hybridization analyses as a highly specific methods for diagnostics of infections and genetic diseases are discussed. Special attention is paid to the chemical approaches to the preparation of non-radioactive probes based on synthetic oligonucleotides and polynucleotides containing biotin, Eu3+ and enzyme labels. Some versions of the hybridization analysis technique are discussed. PMID- 1881391 TI - ["Tie" calorimetry: theory and experiment]. AB - The results of theoretical and experimental investigations of the interaction of ligands to DNA permit to suggest the method of "tie" calorimetry by means of which the thermodynamic parameters of the cooperative transitions of DNA such as helix-coil, B-A and B-Z transitions were obtained. The prominence of the method is that the experimental samples contain such concentration of DNA that intermolecular interaction may be neglected. Moreover the smaller is the magnitude of the measured parameter the greater is the accuracy of the experimentally obtained data. PMID- 1881392 TI - [Study of heat denaturation of human serum albumin in water-alcohol and water salt solutions in the presence of organic ligands]. AB - The method of differential scanning microcalorimetry was used to show a decrease in heat stability of serum albumin in the presence of aliphatic alcohols. In aqueous-alcohol media, the melting temperature, denaturation transition enthalpy were decreased, and the protein intermolecular aggregation enhanced. When the alcohol concentration in aqueous solution was elevated, the number of epsilon amino groups of lysine residues in human serum albumin exposed to the solvent rose from 6-7 in aqueous solution to maximum 20 groups in the aqueous-alcohol solution, respectively. The elevation of ionic strength also induced an increase in the number of exposed lysine residues and was accompanied by an enhancement of protein aggregation. The modification of six amino groups by pyridoxal phosphate or three by glucose in the initial albumin stabilized the protein incubated at 65 degrees-70 degrees C both in the aqueous-alcohol media. At the given concentration and temperature the native protein was denatured and fully aggregated. Aliphatic alcohols displaced fatty acids from the binding sites on the molecule of serum albumin, which resulted in a change in the number of peaks of the melting curve. PMID- 1881393 TI - [Affinity modification of DNA polymerase I from Escherichia coli and its Klenow fragment with nucleotide imidazolides]. AB - Affinity modification of E. coli DNA polymerase I and its Klenow fragment by imidazolides of dNMP (Im-dNMP) and dNTP was studied. DNA polymerase activity of DNA polymerase I was reduced by both Im-dNMP and Im-dNTP. However Im-dNTP does not inactivate of the Klenow fragment. The level of covalent labelling of both enzymes by radioactive Im-dNTP did not exceed 0.01 mol of reagent per mol of enzyme. But the deep inactivation of DNA polymerase I by Im-dNTP was observed. It is likely that this inactivation is due to the formation of intramolecular ether followed by phosphorylation of the carboxyl group. This assumption is strongly supported by the increase of the isoelectrical point of DNA polymerase I after its incubation with Im-dNTP in conditions of enzyme inactivation. All data permit us to suggest that the affinity modification of both enzymes by Im-dNMP and covalent labeling by Im-dNTP takes place without complementary binding of dNTP moiety with the template. However inactivation of DNA polymerase I by Im-dNTP occurs only if the dNTP-moiety is complementary to the template in the template.primer complex. It was shown that His residue was phosphorylated by Im dNMP and Tyr or Ser residues between Met-802 and Met-848 were phosphorylated by Im-dNTP. We suppose that there are two states of DNA polymerase active site for the binding of dNTPs. One of them is independent on the template, in the other state the dNTP hydrogen bond with the template is formed. PMID- 1881394 TI - [Influenza virus proteins: preparation of a soluble M1 polypeptide by means of a stepwise deproteination of virions]. AB - Layer by layer uncoating of influenza A and B viruses with non-ionic detergent (NP-40) at fixed pH was developed. Treatment of virions with NP-40 at neutral or alkaline pH solubilized the lipoprotein envelope and the surface glycopolypeptides HA1 and HA2, but the internal core structures containing matrix protein M1 remained. Exposition of the cores in acidic media (pH 4,5 and lower) selectively solubilized protein M1 and released viral ribonucleoprotein (RNP). The resulting M1 sedimented in a glycerol gradient with a coefficient of 2.8 S and most probably exists as a monomer of 27,000 Da polypeptide. Neutralization of protein M1 with Tris-HC1 at pH 7.0 did not cause aggregation of M1 polypeptides. The described method of viron layer by layer uncoating with non-ionic detergent at fixed pH is suitable for isolation of subvirus structures and individual viral proteins. PMID- 1881396 TI - [Detection of hybridization probes using antibodies to DNA adducts with cis- and trans-diaminodichloroplatinum (II). I. Immunochemical characteristics of DNA modified by cis- and trans-diaminodichloroplatinum (II)]. AB - Rabbit antisera elicited against calf thymus DNA modified cis- and trans diaminedichlorplatinum II (DDP) [Pt/nucleotide ratio - 0.1] contain antibodies specific for Pt-modified DNA immunogen. A specific antibody against DNA-cisDDP and DNA-transDDP was obtained by affinity chromatography. In the ELISA, 3.10(-1 6) mol Pt per micrograms DNA was determined. The epitope structure was determined by using DNA modified with cisDDP and transDDP. PMID- 1881395 TI - [Features of the structure of catalytic subunits of toxins, inhibiting protein synthesis. I. The effect of pH and interaction with the B-chain of ricin]. AB - A comparative study of gelonin and A-chains of ricin, mistletoe lectin I and diphtheria toxin was undertaken. The effect of pH was studied on: a) the conformation of the proteins under study using intrinsic fluorescence; b) interaction of these proteins with ricin B-chain using gel-filtration. Structural stability of the proteins was assessed according to denaturing action of guanidine hydrochloride and temperature, and localization of tryptophan residues was determined using fluorescence quenching by I-, Cs+ and acrylamide. All investigated proteins were shown to undergo the conformational changes when a environment became acidic. In comparison with an intact protein--gelonin, the A chains of ricin, a mistletoe lectin and a diphtheria toxin are less stable. At pH less than 5.0 tryptophan residues became more accessible to quencher and a positive charge of the surrounding area increases (in the case of gelonin it is negatively charged). No reliable interaction of a ricin B-chain with both gelonin and A-chain of diphtheria toxin was observed. The interaction of a ricin B-chain with a A-chain of mistletoe lectin I is weaker than that with ricin A-chain and is practically pH-independent. PMID- 1881398 TI - [Optimal chips for megabase DNA sequencing]. AB - The SHOM method (Sequencing by Hybridization with Oligonucleotide Matrix) developed in 1988 is a new approach to nucleic acid sequencing by hybridization to a octanucleotide matrix composed of an array of immobilized oligonucleotides. The original matrix proposed for sequencing by SHOM had to contain at least 65,536 octanucleotides. The present work describes a new family of matrices for sequencing, which allows one to reduce the number of synthesized oligonucleotides 5-15 times without essentially decreasing the resolving power of the method. PMID- 1881397 TI - [II. Use of antibodies to DNA modified by trans-diaminodichloroplatinum, for identification of specific DNA sequences]. AB - DNA modified by trans diaminedichlorplatinum-II (transDDP) has been suggested as an effective probe for non-isotopic hybridization and high-specific anti-DNA transDDP antibodies with horse radish peroxidase or alkaline phosphotase conjugated antibodies to rabbit Ig and protein A-peroxidase - for hybrids visualization. This method allows to detect 2 pg/mm DNA. PMID- 1881399 TI - Production of interleukin-1 and tumor necrosis factor by cisplatin-treated murine peritoneal macrophages. AB - Supernatants collected from cisplatin-treated macrophages demonstrated enhanced cytotoxicity against actinomycin-D-treated L929 cells and also enhanced the thymocyte proliferation in response to concanavalin A, showing that cisplatin treated macrophages release interleukin-1 (IL-1) and tumor necrosis factor (TNF) into the culture supernatant. The supernatant collected from untreated macrophages showed little TNF and IL-1 activity. The release of TNF and IL-1 was observed to be dependent on the dose and duration of cisplatin treatment. Medium alone containing cisplatin did not enhance thymocyte proliferation and had little cytotoxic effect on actinomycin-D-treated L929 cells. Cisplatin-treated macrophage culture supernatants were chromatographed over a Superose 12 column on an FPLC system. TNF activity eluted in two major peaks with apparent molecular weights of 50-55 and 15-20 kilodaltons, respectively. The kinetics of IL-1 release was also studied. Maximum production and release of IL-1 were observed up to 24 h after cisplatin treatment and then gradually declined. Freeze-thaw lysates of cisplatin-treated macrophages also showed enhanced IL-1 activity. Paraformaldehyde (PFA)-fixed cisplatin-treated macrophages showed significantly enhanced cytotoxic activity against L929 cells as compared to PFA-fixed untreated macrophages. PFA-fixed cisplatin-treated macrophages also enhanced thymocyte proliferation. These results suggest that cisplatin treatment of murine macrophages also results in increased expression of membrane-associated IL-1 and TNF activity. PMID- 1881400 TI - Natural killer cell immunodeficiency in patients with chronic myelogenous leukemia. IV. Interleukin-1 deficiency, gamma-interferon deficiency and the restorative effects of short-term culture in the presence of interleukin-2 on natural killer cytotoxicity, natural killer-target binding and production of natural killer cytotoxic factor. AB - We report herein that defective natural killer (NK) cell cytotoxicity, NK cytotoxic factor (NKCF) production and NK target binding ability of patients with chronic myelogenous leukemia (CML) are functionally restorable after short-term culture (less than 1 week) with recombinant interleukin-2 (rIL-2). We have previously reported that, despite normal to increased numbers of CD16+ large granular lymphocytes, fluorescence-activated-cell-sorted NK cells from CML patients are profoundly defective in NK cell activity and are unable to lyse the CML blast-crisis-derived, NK-sensitive target K562. Since we and others have also previously shown that the defective NK cytotoxicity from CML patients is restorable after 1-4 weeks of incubation with rIL-2, we therefore deemed it important to study the kinetics of IL-2-mediated NK restoration at earlier time intervals (less than 1 week). In the present report, we have demonstrated a significant restoration of NK cell cytotoxicity in CML patients against K562 after 5 days of short-term culture with rIL-2. In addition, recovery of NKCF production and restoration of target-binding capacity to normal levels by NK cells from CML patients were also observed after short-term (less than 1 week) rIL-2 treatment. Finally, we have demonstrated in the present report that adherent cells and peripheral-blood lymphoid cells from CML patients, as compared to normal controls, are unable to produce IL-1 beta and interferon-gamma, respectively, after stimulation with phorbol myristate acetate (IL-1 beta) and phytohemagglutinin-M (interferon-gamma). PMID- 1881401 TI - Inhibition of CFU-G formation by human serum during granulopoiesis after chemotherapy: purification of CFU-G-inhibitory factor and its activities. AB - We found that the sera obtained from patients with acute leukemia (AL) in complete remission or malignant lymphoma (ML) during the recovery phase after chemotherapy completely inhibited the GCT-CM-stimulated growth of allogenic and autologous bone marrow colonies in vitro. We investigated 5 AL patients and 6 ML patients from whom blood samples were taken either every day or every 6 h during the recovery phase after chemotherapy. Colony-inhibitory sera, were detected in all patients, more frequently when the peripheral leukocyte count recovered to about 2,500 x 10(6)/l, but then transiently and at intervals. The colony inhibitory factor purified from the inhibitory sera inhibited the growth of G-CSF responsive colonies in a dose-dependent manner, but no effect on the growth of GM CSF-responsive colonies, CFU-E, or BFU-E, was observed. These results suggest that this factor may play a role in regulating granulopoiesis by inhibiting the differentiation of G-CSF-responsive precursor cells. PMID- 1881402 TI - The genetic toxicology of acridines. AB - Acridine and its derivatives are planar polycyclic aromatic molecules which bind tightly but reversibly to DNA by intercalation, but do not usually covalently interact with it. Acridines have a broad spectrum of biological activities, and a number of derivatives are widely used as antibacterial, antiprotozoal and anticancer drugs. Simple acridines show activity as frameshift mutagens, especially in bacteriophage and bacterial assays, by virtue of their intercalative DNA-binding ability. Acridines bearing additional fused aromatic rings (benzacridines) show little activity as frameshift mutagens, but interact covalently with DNA following metabolic activation (forming predominantly base pair substitution mutations). Compounds where the acridine acts as a carrier to target alkylating agents to DNA (e.g. the ICR compounds) cause predominantly frameshift as well as base-pair substitution mutations in both bacterial and mammalian cells. Nitroacridines may act as simple acridines or (following nitro group reduction) as alkylating agents, depending upon the position of the nitro group. Acridine-based topoisomerase II inhibitors, although frameshift mutagens in bacteria and bacteriophage systems, are primarily chromosomal mutagens in mammalian cells. These mutagenic activities are important, since the compounds have considerable potential as clinical antitumour drugs. Although evidence suggests that simple acridines are not animal or human carcinogens, a number of the derived compounds are highly active in this capacity. PMID- 1881403 TI - The genetic toxicology of 5-bromodeoxyuridine in mammalian cells. AB - The thymidine analog, BrdUrd, induces many biological responses which are of importance to the field of genetic toxicology and related disciplines. These include the induction of SCE, specific-locus mutations, and toxicity, inhibition of cell proliferation, and the expression of fragile sites in the human genome. In early models which addressed the mechanisms of the biological effects of BrdUrd exposure, two pathways were proposed to account for the induction of the biological responses. Incorporation of the enol form of BrdUrd into the nascent DNA strand after pairing with deoxyguanosine was proposed as one pathway, whereas the incorporation of BrdUrd opposite adenosine in place of thymidine was proposed as the second pathway. Many novel and sophisticated techniques have been applied to the study of the mechanism of the induction of biological effects by BrdUrd leading to a substantial increase in our understanding of these mechanisms. However, the experimental evidence clearly supports the contention that BrdUrd exerts its effects on eukaryotic cells through mechanisms similar to those originally proposed to explain the genotoxicity of BrdUrd. PMID- 1881404 TI - Increased frequency of sister-chromatid exchange and chromatid breaks in lymphocytes after treatment of human volunteers with therapeutic doses of paracetamol. AB - Paracetamol was given to 10 healthy human volunteers in 3 doses of 1 g each during a period of 8 h. Blood samples for lymphocyte cultures were taken before and 24 h after paracetamol administration. A small but significant increase was found in the frequency of sister-chromatid exchanges (SCE) after intake of paracetamol (0.187 +/- 0.030 per chromosome before and 0.208 +/- 0.024 per chromosome after). After exposure the mean frequency of chromatid breaks per 100 cells was significantly increased (2.16 +/- 1.33 versus 0.33 +/- 0.50 before exposure). Exposure of human lymphocytes in vitro showed that concentrations of paracetamol above 0.1 mM induced inhibition of replicative DNA synthesis. Increased SCE was found in lymphocytes exposed to 1-10 mM paracetamol for 2 h. Furthermore, 0.75-1.5 mM paracetamol exposure for 24 h increased the frequency of chromatid and chromosome breaks in the lymphocytes. The paracetamol-induced SCE and chromosome aberrations may be secondary effects of paracetamol-induced inhibition of DNA synthesis or due to covalent binding of paracetamol metabolite(s) to DNA. PMID- 1881405 TI - Aflatoxin-induced structural chromosomal changes and mitotic disruption in mouse bone marrow. AB - Ascorbic acid in a dose proportional to the human therapeutic dose (500 mg/day), when administered to Swiss albino mice along with a dietary concentration of aflatoxin B1, decreases the incidence of toxin-induced chromosomal abnormalities in the bone marrow cells. Treatment with the toxin alone (6 and 12 weeks) did not produce any differences in clastogenicity. The vitamins, when administered along with the toxin for 6 weeks, seemed to nullify more of the structural changes than of the mitotic disruptions. In 12-week treatment, more structural and fewer disruption-type abnormalities were found. PMID- 1881406 TI - Indoor sources of mutagenic aerosol particulate matter: smoking, cooking and incense burning. AB - The emission of aerosol particles and their mutagenic activity as well as the emission of some gaseous pollutants has been studied experimentally in order to compare the emission from some indoor pyrolysis processes. Cigarette (tobacco and herbal) smoking, incense and mosquito-coil burning and frying of experimental lean minced pork emitted particulate matter. Their extracts were mutagenic in the Ames Salmonella test with TA98 and activation as well as, with a higher response, in a microsuspension test with the same strain and activation condition. The response of the particles from the smoking and burning processes varied from 3000 to 50,000 revertants per gram of smoked or burnt material in the conventional Salmonella test and from 50,000 to 350,000 revertants per gram in the microsuspension assay. The frying of lean minced pork gave an airborne emission of about 53 and 560 revertants per gram of fried pork, respectively, in the 2 assays. The frying of some common food items following cookbook recipes also emitted mutagenic aerosol particles but the emitted activity was less than that in the pork experiment. Carbon monoxide, isoprene and benzene were present in the emissions from the smoking and burning processes but were not detectable in the frying fumes. The results suggest that incense and mosquito-coil burning can cause indoor air pollution akin to that from cigarette smoking. Indoor air pollution from cooking requires further study. PMID- 1881407 TI - Cytogenetic surveillance of tobacco-areca nut (mava) chewers, including patients with oral cancers and premalignant conditions. AB - Three cytogenetic endpoints were studied in non-chewing healthy controls and 3 groups of tobacco-areca nut chewers, viz. normal chewers, chewers with oral submucous fibrosis and chewers with oral cancer. Frequencies of sister-chromatid exchanges and chromosome aberrations in peripheral blood lymphocytes and of micronucleated cells in exfoliated buccal mucosa were evaluated. All the parameters showed statistically significant elevations in all 3 groups of chewers compared to the controls. The data indicate possible application of the parameters as sensitive endpoints for monitoring tobacco-areca nut chewers, the group of individuals at higher risk of developing oral cancer, the commonest cancer among Indian males. PMID- 1881408 TI - Studies on the utilization of a plant SCE test in detecting potential mutagenic agents. AB - In this paper a modified procedure for sister-chromatid differentiation in plant cells is reported. Using this procedure some chemicals were tested for SCE induction in Vicia faba, Hordeum vulgare and Secale cereale. The chemicals tested were ethanol, chromium oxide, sodium saccharin, fluorouracil, ascorbic acid (vitamin c), omethoate and phenol. The experimental results showed that most of them induced SCE increases in mouse spleen cells, human lymphocytes and plant cells. The increase of SCEs per cell in plant cells is in agreement with that found in human lymphocytes or in mouse spleen cells. In our opinion, the utilization of SCE in plants is a simple and inexpensive technique for detecting potential mutagenic agents in the environment. PMID- 1881409 TI - Measuring personal exposure to airborne mutagens and nicotine in environmental tobacco smoke. AB - The exposure of individuals to environmental tobacco smoke (ETS) is of increasing public health concern because epidemiological studies have associated passive smoking with increased risk of a variety of adverse health effects among non smokers including lung cancer. As a way to measure individual exposure to the mutagenic compounds in the complex mixture of ETS, we used a sensitive Salmonella/microsome micro pre-incubation (microsuspension) assay to detect mutagenicity of particulate matter collected on filters from low volume (1.7 1/min flow rate) personal sampling pumps. Airborne nicotine was collected concurrently as a marker for ETS exposure. In pilot-field studies, individual exposure to ETS was measured in two separate indoor environments in which smokers were present: a gambling casino and a bingo parlor. Total suspended particulate matter (TSP) was collected on filters worn near the breathing zone of non-smoking individuals. Sampling times ranged from 40 min to 6 h. All extracts of filters had detectable levels of mutagenic activity (TA98, +S9) resulting in airborne mutagenic activity concentrations of 500-5000 rev/m3. The mutagenic activity of the filters from the casino and bingo parlors was significantly correlated with total particulate matter per filters (n = 12; Rho = 0.85, p less than 0.01) and with airborne nicotine per filter (n = 12; Rho = 0.95, p less than 0.01). The microsuspension assay was sufficiently sensitive to detect the mutagens associated with extracts of particulate matter from low volume samples (0.2-0.6 m3) in these indoor environments over a relatively short sampling time, and could be useful in studies of personal exposure to the mutagens in environmental tobacco smoke. Further, airborne nicotine concentrations were highly correlated with airborne mutagenicity and the mutagenic activity associated with ETS could therefore be estimated by the concentrations of nicotine. PMID- 1881410 TI - Influence of vegetable oil vehicles on bone-marrow proliferation in the mouse micronucleus test. AB - The detection of genotoxins in the mouse bone-marrow micronucleus (MN) test is sensitive to factors which may inhibit bone-marrow proliferation. We have shown that three commercially available cooking oils (olive, peanut and sunflower seed oils), commonly used as vehicles in toxicological tests, were able to induce a cytotoxic effect in mouse bone marrow. The effects observed were reversible and the magnitude of the responses varied with the oil administered. The results suggest a need to examine vehicle effects when conducting the MN test. PMID- 1881411 TI - Chrysotile and amosite asbestos induce germ-line aneuploidy in Drosophila. AB - Asbestos toxicity is a problem of considerable public concern and debate, however little is known regarding the biological targets of asbestos fibers. Prompted by reports that asbestos induces aneuploidy in cultured mammalian cells, we have investigated whether asbestos induces germ-line aneuploidy in Drosophila melanogaster. Using the ZESTE genetic test system, we have shown that both chrysotile and amosite asbestos induce sex-chromosome aneuploidy in Drosophila oocytes. Chrysotile appeared to be the more effective agent because it induced approximately equal frequencies of chromosome gain and chromosome loss, while amosite induced chromosome loss only. Two other asbestiform minerals, crocidolite and tremolite, were ineffective in this assay system. These results suggest that possible germ-line effects of asbestos should be considered in evaluating its potential impact on human health. PMID- 1881412 TI - Plasmid pSK1002-mediated mutator effect and SOS response and SOS mutagenesis of 2,5-dichloronitrobenzol in Salmonella typhimurium. AB - The plasmid pSK1002 (umuC'-'lacZ) could increase the number of revertants induced by methyl methanesulfonate (MMS) and 4-nitroquinoline-N-oxide (4NQO) in Salmonella typhimurium TA 1535 (his-). The values induced by N-methyl-N'-nitro-N nitrosoguanidine (MNNG) were not different irrespective of the presence or absence of plasmid. However, the plasmid pKM101-mediated mutagenesis-enhancing effect was much greater than that mediated by pSK1002 as induced by the 3 mutagens mentioned above. Moreover, the plasmid pSK1002 could induced umu mediated SOS response in the presence of any of these 3 mutagens or of mitomycin C, and a dose-response relationship was evident. It shows that pSK1002 (umuC' 'lacZ) has a dual biological effect, namely a mutator effect and the effect of inducing the SOS response. Besides, this study has proved SOS mutagenesis of 2,5 dichloronitrobenzol (2,5-DCNB) because of the dual indicator nature of pSK1002. Therefore, it is probable that pSK1002 could be further developed and applied in studying the relation between the SOS response and mutagenesis and in identifying environmental SOS mutagens. PMID- 1881413 TI - Increased mutation rate in bacteria overexpressing a cloned foreign gene. AB - Escherichia coli cells growing slowly as a result of the overexpression of a cloned foreign gene were shown to exhibit an increased mutation rate in the foreign gene as well as in several non-selected markers. This phenomenon is discussed in terms of the model proposed by Hall (1990). PMID- 1881414 TI - Simultaneous micronucleus and chromosome aberration assessment in the rat. AB - Using a cellulose column fractionation procedure to eliminate nucleated cells for micronucleus assessment, micronucleus and chromosome aberration endpoints in the same animal were compared in male and female rats following i.p. injection with cyclophosphamide (CP). Groups of 5 Wistar rats per sex were given single doses of CP at 0, 20, or 40 mg/kg. Two hours prior to sacrifice, animals were given colchicine (4 mg/kg) to arrest cells in metaphase. One femur from each animal was used for micronucleus assessment and the other for chromosome aberration assessment. In the micronucleus assessment, 2000 polychromatic erythrocytes (PCEs) per animal and in the chromosome aberration assessment, 50 metaphase cells per animal were scored. This experiment was repeated once. In both experiments, significant increases in micronucleated PCEs and chromosome aberrations were noted at both doses of CP in both sexes. In general, the clastogenic effects of CP were more pronounced in males than females. Both doses of CP caused a decrease in the proportion of PCEs and in mitotic index in both experiments, indicating toxicity of CP to the bone marrow. These results show the usefulness of this rat model for simultaneous evaluation of two cytogenetic endpoints in the same animal and indicate that assessment of MNPCE frequency in the bone marrow of male rats may be an appropriate model for screening test substances for in vivo clastogenic activity in this species. PMID- 1881415 TI - Mutagenicity of wood smoke condensates in the Salmonella/microsome assay. AB - Smoke condensates of woods used for food preservation and aromatization in Nigeria were tested for mutagenic activity using Salmonella typhimurium TA98 and TA100. The woods were: white mangrove (Avicennia nitida), red mangrove (Rhizophora racemosa), mahogany Khaya sp.), abura (Mitragyna ciliata), alstonia (Alstonia boonei) and black afara (Terminalia ivorensis). Cigarette tar was tested for comparison. The condensates induced dose-dependent increases in the number of His+ revertants mainly with S9 mix. With the exception of mahogany and cigarette smoke condensate, the smoke condensates induced more revertants/microgram condensate in TA100 than in TA98. The number of revertants/microgram condensate ranged between 0.04 and 0.9 for the wood smoke condensates and was 0.12 for the cigarette smoke in TA100. The range was between 0.1 and 0.30 for the wood smoke condensates and 0.18 revertants/microgram condensate for cigarette smoke condensate in TA98. Concentrations of 7 polycyclic aromatic hydrocarbons (PAHs) in the condensates were determined namely, pyrene, benzo[a]pyrene, benz[a]anthracene, benzo[k]fluoranthene, benzo[b]chrysene, benzo[g,h,i]perylene and dibenzo[a,e]pyrene. The condensates contained varying concentrations of the individual PAHs and those with higher concentrations generally showed greater mutagenic activities. However, the order of mutagenic potency in the bacterial strains differed from the order of PAH concentrations, which were lower than the concentrations at which they are reported to induce mutations. When 6 of the PAHs were mixed in the concentrations in which they were found in the individual condensates, the mixtures did not induce mutation so that the contribution of the PAHs to the mutagenic activities of the condensates could not be determined. PMID- 1881416 TI - Correlations between antepartum maternal metabolism and intelligence of offspring. AB - BACKGROUND: It is not clear to what extent maternal metabolism during pregnancy affects the cognitive and behavioral function of the offspring by altering brain development in utero. To investigate this question, we correlated measures of metabolism in pregnant diabetic and nondiabetic women with the intellectual development of their offspring. METHODS: The study included 223 pregnant women and their singleton offspring: 89 women had diabetes before pregnancy (pregestational diabetes mellitus), 99 had the onset of diabetes during pregnancy (gestational diabetes mellitus), and 35 had normal carbohydrate metabolism during their pregnancy. We correlated measures of maternal glucose and lipid metabolism (fasting plasma glucose levels, hemoglobin A1c levels, episodes of hypoglycemia, episodes of acetonuria, and plasma beta-hydroxybutyrate and free fatty acid levels) with two measures of intellectual development in the offspring--the mental development index of the Bayley Scales of Infant Development, given at the age of two years, and the Stanford--Binet Intelligence Scale, given at the ages of three, four, and five years and expressed as an average of the three scores. RESULTS: After correction for socioeconomic status, race or ethnic origin, and patient group, the children's mental-development-index scores at the age of two years correlated inversely with the mothers' third-trimester plasma beta hydroxybutyrate levels (r = -0.21, P less than 0.01); the average Stanford-Binet scores correlated inversely with third-trimester plasma beta-hydroxybutyrate (r = -0.20, P less than 0.02) and free fatty acid (r = -0.27, P less than 0.002) levels. No other correlations were significant. Including various perinatal events (e.g., prematurity and acidemia) in the analyses did not alter the results. CONCLUSIONS: Maternal diabetes during pregnancy may affect behavioral and intellectual development in the offspring. The associations between gestational ketonemia in the mother and a lower IQ in the child warrant continued efforts to avoid ketoacidosis and accelerated starvation in all pregnant women. PMID- 1881417 TI - Contractile properties of the human diaphragm during chronic hyperinflation. AB - BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation. We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm. METHODS: In eight patients with COPD and five control subjects of similar age, the transdiaphragmatic pressure generated by the twitch response to phrenic-nerve stimulation was recorded at various base-line lung volumes, from functional residual capacity to total lung capacity, and during relaxation and graded voluntary efforts at functional residual capacity (twitch occlusion). RESULTS: At functional residual capacity, the twitch transdiaphragmatic pressure ranged from 10.9 to 26.6 cm of water (1.07 to 2.60 kPa) in the patients and from 19.8 to 37.1 cm of water (1.94 to 3.64 kPa) in the controls, indicating considerable overlap between the two groups. The ratio of esophageal pressure to twitch transdiaphragmatic pressure, an index of the inspiratory action of the diaphragm, was -0.50 +/- 0.05 in the patients, as compared with -0.43 +/- 0.02 in the controls (indicating more efficient inspiratory action in the patients than in the controls). At comparable volumes, the twitch transdiaphragmatic pressure and esophageal-to-transdiaphragmatic pressure ratio were higher in the patients than in normal subjects, indicating that the strength and inspiratory action of the diaphragm in the patients were actually better than in the controls. Twitch occlusion (a measure of the maximal activation of the diaphragm) indicated near-maximal activation in the patients with COPD, and the maximal transdiaphragmatic pressure was 106.9 +/- 13.8 cm of water (10.48 +/- 1.35 kPa). CONCLUSIONS: The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function. PMID- 1881418 TI - Inflammatory bowel disease (1) PMID- 1881419 TI - Insulin resistance--mechanisms, syndromes, and implications. PMID- 1881420 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 39-1991. A 46-year-old man with fever, a cough, and bilateral pulmonary nodules. PMID- 1881421 TI - The diaphragm in COPD. Better than expected, but not good enough. PMID- 1881422 TI - HIV transmission to women in stable relationships. PMID- 1881423 TI - Homocysteinemia: a risk factor for vascular disease. PMID- 1881424 TI - Effect of the age at which smoking begins on frequency of smoking in adulthood. PMID- 1881425 TI - Invasive external otitis after removal of impacted cerumen by irrigation. PMID- 1881426 TI - Medical aspects of Operation Desert Storm. PMID- 1881428 TI - Hungarian science faces sweeping reforms. PMID- 1881427 TI - The effect of the Gulf crisis on the children of Iraq. PMID- 1881429 TI - Medical research. UK ethics guidelines. PMID- 1881430 TI - MITI reveals 1992 budget. PMID- 1881431 TI - US government orders new look at dioxin. PMID- 1881433 TI - Mitochondrial protein charge. PMID- 1881432 TI - Gene therapy. Muscle transfection made easy. PMID- 1881434 TI - The B-cell antigen receptor of the five immunoglobulin classes. AB - Several proteins associate with surface IgM to form the antigen receptor. We show that just two, the alpha and beta associated chains, are sufficient to reconstitute an IgM surface receptor in fibroblasts. Contrary to expectation, a common alpha chain associates with all five immunoglobulin classes. We propose that B-cell antigen receptors consist of a common alpha/beta heterodimer associated with each immunoglobulin class. But the classes differ both in the glycosylation of their associated alpha chain and in their dependence on alpha/beta for surface transport. PMID- 1881435 TI - Is colour vision possible with only rods and blue-sensitive cones? AB - At night all cats are grey, but with the approach of dawn they take on colour. By starlight, a single class of photoreceptors, the rods, function, whereas by daylight, three classes, the blue-, green- and red-sensitive cones, are active and provide colour vision. Only by comparing the rates of quantal absorption in more than one photoreceptor class is colour vision possible. Although the comparisons generally take place between the cones, they can involve the rods as well. Here we investigate the wavelength discrimination of an extremely rare group of individuals, blue-cone monochromats, who have only rods and one class of cones. We find that these individuals can distinguish wavelengths (440 to 500 nm) in the twilight region where the rods and blue-sensitive cones are simultaneously active. PMID- 1881436 TI - Carboxy-terminal truncation activates glp-1 protein to specify vulval fates in Caenorhabditis elegans. AB - The glp-1 and lin-12 genes encode homologous transmembrane proteins that may act as receptors for cell interactions during development. The glp-1 product is required for induction of germ-line proliferation and for embryogenesis. By contrast, lin-12 mediates somatic cell interactions, including those between the precursor cells that form the vulval hypodermis (VPCs). Here we analyse an unusual allele of glp-1, glp-1(q35), which displays a semidominant multivulva phenotype (Muv), as well as the typical recessive, loss-of-function Glp phenotypes (sterility and embryonic lethality). We find that the effects of glp 1(q35) on VPC development mimic those of dominant lin-12 mutations, even in the absence of lin-12 activity. The glp-1(q35) gene bears a nonsense mutation predicted to eliminate the 122 C-terminal amino acids, including a ProGluSerThr (PEST) sequence thought to destabilize proteins. We suggest that the carboxy terminus bears a negative regulatory domain which normally inactivates glp-1 in the VPCs. We propose that inappropriate glp-1(q35) activity can substitute for lin-12 to determine vulval fate, perhaps by driving the VPCs to proliferate. PMID- 1881437 TI - Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. AB - Duchenne's muscular dystrophy (DMD), which affects one in 3,500 males, causes progressive myopathy of skeletal and cardiac muscles and premature death. One approach to treatment would be to introduce the normal dystrophin gene into diseased muscle cells. When pure plasmid DNA is injected into rodent skeletal or cardiac muscle, the cells express reporter genes. We now show that a 12-kilobase full-length human dystrophin complementary DNA gene and a 6.3-kilobase Becker like gene can be expressed in cultured cells and in vivo. When the human dystrophin expression plasmids are injected intramuscularly into dystrophin deficient mdx mice, the human dystrophin proteins are present in the cytoplasm and sarcolemma of approximately 1% of the myofibres. Myofibres expressing human dystrophin contain an increased proportion of peripheral nuclei. The results indicate that transfer of the dystrophin gene into the myofibres of DMD patients could be beneficial, but a larger number of genetically modified myofibres will be necessary for clinical efficacy. PMID- 1881438 TI - Academic promotion in Italy. PMID- 1881439 TI - Is homosexuality hard-wired? PMID- 1881440 TI - Allan Charles Wilson (1934-1991) PMID- 1881441 TI - More genome ethics. PMID- 1881442 TI - The transmission of AIDS. PMID- 1881443 TI - Stem cells. PMID- 1881444 TI - Japanese science agency targets space, genome. PMID- 1881445 TI - Clinical trails. Blazing an ethical trail. PMID- 1881446 TI - Genetic screening. California tackles insurance. PMID- 1881447 TI - Scientific societies. Ethics rules provoke storm. PMID- 1881448 TI - Binding of synaptotagmin to the alpha-latrotoxin receptor implicates both in synaptic vesicle exocytosis. AB - A vertebrate neurotoxin, alpha-latrotoxin, from black widow spider venom causes synaptic vesicle exocytosis and neurotransmitter release from presynaptic nerve terminals. Although the mechanism of action of alpha-latrotoxin is not known, it does require binding of alpha-latrotoxin to a high-affinity receptor on the presynaptic plasma membrane. The alpha-latrotoxin receptor seems to be exclusively at the presynaptic plasmamembrane. Here we report that the alpha latrotoxin receptor specifically binds to a synaptic vesicle protein, synaptotagmin, and modulates its phosphorylation. Synaptotagmin is a synaptic vesicle-specific membrane protein that binds negatively charged phospholipids and contains two copies of a putative Ca(2+)-binding domain from protein kinase C (the C2-domain), suggesting a regulatory role in synaptic vesicle fusion. Our findings suggest that a physiological role of the alpha-latrotoxin receptor may be the docking of synaptic vesicles at the active zone. The direct interaction of the alpha-latrotoxin receptor with a synaptic vesicle protein also suggests a mechanism of action for this toxin in causing neurotransmitter release. PMID- 1881449 TI - Biotechnology. Will milk shake up industry? PMID- 1881450 TI - Failure of wild-type or a mutant form of protein kinase C-alpha to transform fibroblasts. AB - A mutant form of the alpha-isoform of protein kinase C (PKC) was recently isolated from an ultraviolet radiation-induced murine fibrosarcoma cell line and reported to transform mouse BALB/c 3T3 fibroblasts on transfection. Four point mutations in the regulatory domain were assumed to be responsible for its oncogenicity and unusual preference for membrane localization. Here, we report that overexpression of the reported mutant PKC alpha complementary DNA in three fibroblast cell lines, including BALB/c 3T3, does not enable these cells to grow in soft agar or nude mice. In addition, this mutant PKC alpha form seems to be indistinguishable from the wild-type PKC alpha with respect to its dependence on cofactors, phorbol ester binding, subcellular distribution and its effects on growth and morphology. These results fail to confirm the previous study and indicate that overexpression of either the wild-type or the reported mutant form of PKC alpha does not transform rodent fibroblasts. PMID- 1881451 TI - Biotechnology. EC look to animal patents. PMID- 1881452 TI - Oncogenic germ-line mutations in Sp1 and ATF sites in the human retinoblastoma gene. AB - The transcription of a eukaryotic gene is a consequence of intricate interactions between members of a set of transcription factors. We describe here evidence indicating that at least two distinct DNA-binding factors play an important part in the transcription of the human retinoblastoma gene (Rb). One of the factors reacts with a sequence overlapping with a potential Sp1 recognition sequence in the promoter region of the gene, the other with a nearby ATF recognition sequence. We have identified two naturally occurring point mutations in these recognition sequences that cause hereditary retinoblastoma. The nuclear factors do not bind to the mutant sequences. We infer that these nuclear factors are necessary for the expression of the Rb gene and the suppression of cancer. PMID- 1881453 TI - Putative receptor for the cytoplasmic inactivation gate in the Shaker K+ channel. AB - Inactivation of ion channels is important in the control of membrane excitability. For example, delayed-rectifier K+ channels, which regulate action potential repolarization, are inactivated only slowly, whereas A-type K+ channels, which affect action potential duration and firing frequency, have both fast and slow inactivation. Fast inactivation of Na+ and K+ channels may result from the blocking of the permeation pathway by a positively charged cytoplasmic gate such as the one encoded by the first 20 amino acids of the Shaker B (ShB) K+ channel. We report here that mutation of five highly conserved residues between the proposed membrane-spanning segments S4 and S5 (also termed H4) of ShB affects the stability of the inactivated state and alters channel conductance. One such mutation stabilizes the inactivated state of ShB as well as the inactivated state induced in the delayed-rectifier type K+ channel drk1 by the cytoplasmic application of the ShB N-terminal peptide. The S4-S5 loop, therefore, probably forms part of a receptor for the inactivation gate and lies near the channel's permeation pathway. PMID- 1881454 TI - The case against. PMID- 1881455 TI - 5-Hydroxytryptamine4 receptors mediate relaxation of the rat oesophageal tunica muscularis mucosae. AB - The present study was designed to characterize an "atypical" 5-hydroxytryptamine (5-HT) receptor mediating relaxation of the rat oesophageal tunica muscularis mucosae. All experiments were performed under equilibrium conditions, using pargyline to inhibit the oxidative deamination of indoleamines, and cocaine and corticosterone to inhibit neuronal and extraneuronal uptake. Under these conditions 5-HT (0.3-1000 nmol/l) produced a concentration-dependent relaxation of carbachol-induced tension. The concentration-effect curve to 5-HT was unaffected by potent antagonists for 5-HT1, 5-HT2, 5-HT3 and so called 5-HT1P receptors (metergoline, methysergide, ketanserin, ondansetron, N-acetyl-5 hydroxytryptophyl-5-hydroxytryptophan amide), but was antagonized competitively by ICS 205-930 (pA2 = 6.7). Responses to 5-HT were mimicked by other indoleamines and substituted benzamides with the following order of potency: 5-HT greater than or equal to 5-methoxytryptamine greater than cisapride = alpha-methyl-5-HT = (S) zacopride = renzapride greater than (RS)-zacopride greater than 5-carboxamido tryptamine = metoclopramide = (R)-zacopride greater than tryptamine greater than 2-methyl-5-HT. ICS 205-930 afforded similar pA2 values (6.0-6.7) against each agonist, indicating a common site of action. Concentration-effect curves to 5-HT were not affected by tetrodotoxin or indomethacin, suggesting that 5-HT-induced relaxation of the tunica muscularis mucosae was mediated via a post-junctional receptor, independent of endogenous prostanoids. The pharmacological profile of the 5-HT receptor in the rat oesophageal tunica muscularis mucosae correlates well with the 5-HT4 receptor characterized recently in both the CNS and gastro intestinal tract. PMID- 1881456 TI - Repeated SKF 38393 and nigrostriatal system neuronal responsiveness: functional down-regulation is followed by up-regulation after withdrawal. AB - The effects of chronic administration of the D1 dopamine (DA) agonist SKF 38393 on the basal activity and electrophysiological and pharmacological responsiveness of nigrostriatal DA neurons were examined by means of extracellular, single-unit recording techniques. Chronic D1 stimulation failed to alter either the basal activity of DA neurons or the potency of quinpirole to induce inhibition of these cells. However, 28-day SKF 38393 treatment (but not 14-day treatment) eliminated the ability of subsequent (24 h later) acute SKF 38393 to alter the rate dependent nature of quinpirole-induced inhibition. In contrast, one week after a 28-day SKF 38393 treatment we found that quinpirole-induced inhibition by itself was no longer rate-dependent, an effect which was reversed by acute pretreatment with the D1 antagonist SCH 23390. This latter finding is suggestive of enhanced endogenous D1 tone. Similarly, 28-day SKF 38393 treatment eliminated the effect of subsequent acute SKF 38393 on sciatic nerve stimulation-induced inhibition of nigrostriatal DA neurons, whereas one week after the chronic D1 regimen these cells were highly sensitive to acute D1 enhancement of the response to sciatic nerve stimulation. In order to address the postsynaptic effects of chronic D1 stimulation, the influence of iontophoretically administered SKF 38393 was examined on type I caudate neurons. Again, 28-day SKF 38393 treatment resulted in reduced sensitivity of caudate neurons tested 24 h later, and an enhanced sensitivity was observed one week after the completion of chronic SKF 38393 administration. Thus, chronic SKF 38393 induced functional desensitization of D1 receptors, but one-week withdrawal was followed by sensitization. PMID- 1881457 TI - N2-acetylphenelzine: effects on rat brain GABA, alanine and biogenic amines. AB - The neurochemical properties of N2-acetylphenelzine were compared with those of phenelzine in a rat model. N2-Acetylphenelzine is a relatively potent inhibitor of monoamine oxidase-A and -B and causes increases in whole-brain levels of noradrenaline and 5-hydroxytryptamine, and decreases in homovanillic acid, 5 hydroxyindole-3-acetic acid, and 3,4-dihydroxyphenylacetic acetic after acute i.p. administration of the drug. Phenelzine is a more potent monoamine oxidase inhibitor than is N2-acetylphenelzine. The most marked difference in the profile was that N2-acetylphenelzine had no effect on whole brain levels of the amino acid neurotransmitters alanine and gamma-aminobutyric acid, whereas phenelzine caused dramatic increases. Acetylation of phenelzine at the N2 position presumably interferes with the inhibition of the transaminase enzymes for gamma aminobutyric acid and alanine. PMID- 1881458 TI - Comparative studies on the anorectic activity of d-fenfluramine in mice, rats, and guinea pigs. AB - The present study compares the anorectic activity of d-fenfluramine and its metabolite d-norfenfluramine in three animal species. d-Fenfluramine and d norfenfluramine show anorectic activity at increasing doses (ED50) in rats, guinea pigs, and mice, d-norfenfluramine being more active than d-fenfluramine in all three species. Equiactive anorectic activities are reached with different brain levels of d-fenfluramine and d-norfenfluramine, guinea pigs being the most sensitive species, followed by rats then mice. The metabolite most probably plays a major role in the anorectic effect of d-fenfluramine in guinea pigs, contributes to the anorectic activity in rats, but adds little to the action of the parent drug in mice. The different sensitivity to d-fenfluramine and d norfenfluramine in these three species does not appear to be explained by a number of biochemical parameters, including serotonin uptake or release, receptor subtypes, or 3H-d-fenfluramine binding and uptake. PMID- 1881460 TI - The influence of calcium antagonists on the adenine nucleotide metabolism in the guinea-pig working heart during ischaemia and reperfusion. AB - With the aim of gaining more insight into the metabolism of adenine nucleotides in working normoxic guinea-pigs and in hearts subjected to 45 min of global ischaemia and subsequent reperfusion for 25 min, we evaluated the effect of nifedipine, verapamil, diltiazem, bepridil, CERM 11956, lidoflazine, mioflazine and dipyridamole on the adenine nucleotide catabolite levels in these hearts. The drugs were applied at the concentrations that reduced the aortic dP/dt of normoxic working hearts by 10% (EC10) and 30% (EC30). In globally ischaemic hearts there was a large accumulation of adenine nucleotide catabolites. Inosine proved to be the major catabolite. The drugs, with the exception of bepridil, CERM 11956 and dipyridamole (3 mumol/l), decreased the accumulation of catabolites. In hearts treated with mioflazine and dipyridamole the amount of adenosine increased. A deficit in the balance between adenine nucleotides and catabolites indicated that in globally ischaemic hearts there was a large accumulation of inosine monophosphate. Indeed, a substantial amount of inosine monophosphate was determined in untreated hearts, and hearts treated with nifedipine (EC30) and mioflazine (EC10). During the first 5 min of reperfusion a large quantity of catabolites, mainly inosine, was washed out. During 20 min of subsequent reperfusion in untreated hearts and in nifedipine and mioflazine treated hearts the efflux of catabolites returned to normoxic values. Similar to the effect in ischaemic hearts, in early perfusate from lidoflazine, mioflazine and dipyridamole-treated hearts the adenosine/inosine ratio was increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881459 TI - Coronary vasodilation induced by captopril and zofenoprilat: evidence for a prostaglandin-independent mechanism. AB - In this study, the vasodilating properties of captopril and zofenoprilat, two angiotensin-converting enzyme (ACE) inhibitors containing the sulfhydryl group, are investigated in the isolated rat heart. It is demonstrated that both compounds increase coronary flow in a dose-dependent manner. However, the mean pD2 of zofenoprilat appears to be significantly higher than the mean pD2 of captopril (4.55 +/- 0.06 and 3.35 +/- 0.02 respectively), indicating that zofenoprilat is about ten times more potent in increasing coronary flow than captopril. Possibly this difference in potency between captopril and zofenoprilat can be explained by their physicochemical properties. Since zofenoprilat is more lipophilic than captopril, its concentration in cardiac and vascular tissues at distribution equilibrium is thought to be higher than the tissue concentration of captopril, which may result in a more pronounced vasodilatory action. The precise mechanism of coronary vasodilation induced by ACE inhibitors containing the sulfhydryl group is not yet understood. Several factors have been proposed, such as stimulation of prostacyclin production. However, in this study, concomitant administration of 10(-6) mol/l acetylsalicylic acid shows no antagonism, indicating that under normoxic conditions the vasodilatory effects of captopril and zofenoprilat are independent of the production of vasodilating prostaglandins. Therefore, other factors than stimulation of prostacyclin synthesis seem to be involved, such as prevention of bradykinin breakdown and/or potentiation of endothelium derived relaxing factor (EDRF). Furthermore, despite a marked inhibition of prostacyclin production, 10(-6) mol/l acetylsalicylic acid itself has no effect on coronary flow. These results suggest that prostacyclin does not play an important role in the regulation of coronary flow, at least in the normoxic isolated rat heart. PMID- 1881461 TI - Protective effect of N-acetylcysteine on ischaemia-induced myocardial damage in canine heart. AB - The glutathione redox pathway is an important antioxidant system in the myocardium. N-Acetylcysteine is a low molecular weight glutathione precursor that has been used clinically to replenish glutathione stores. The present study was aimed at evaluating the protective effect of N-acetylcysteine on myocardial damage resulting from permanent coronary occlusion (without reperfusion) in anaesthetized dogs. N-Acetylcysteine (150 mg kg-1 i.v.) administered 2 min before occlusion reduced infarct size in dogs subjected to 24 h ischemia. The infarct size as a percentage of the area at risk was 86.8 +/- 3.6% (n = 11) in control (saline-treated) dogs and 68.2 +/- 2.4% (n = 7; P less than 0.05 vs control) in N acetylcysteine-treated animals. Haemodynamic variables (heart rate, mean arterial pressure and rate-pressure product) were similar in the control and the treated group. Regional myocardial blood flow was determined with radioactive microspheres in ischaemic and non-ischaemic zones before occlusion and 3 h post occlusion. N-Acetylcysteine did not influence the regional distribution of myocardial blood flow. The myocardial content of reduced glutathione was significantly (P less than 0.05) decreased 3 h post-occlusion (0.53 +/- 0.19 mumol/g-1; n = 5) compared to either pre-occlusion values (0.94 +/- 0.03 mumol/g 1; n = 8) or values 3 h post-occlusion in sham-operated animals (0.93 +/- 0.15 mumol/g-1; n = 5). Depletion of myocardial glutathione 3 h post-occlusion was not observed in dogs treated with N-acetylcysteine (0.87 +/- 0.11 mumol/g-1; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881462 TI - A selective uricosuric action of AA-193 in rats. Comparison with its effect on PAH secretion in vivo and in vitro. AB - We evaluated the uricosuric action of AA-193 by comparing it with the effect on PAH secretion in rats, using in vivo and in vitro techniques. The i.v. administration of AA-193 elevated the fractional excretion of urate (FEurate) significantly in a dose-dependent manner at doses from 0.1 to 10 mg/kg. Only at the highest dose of 10 mg/kg did AA-193 cause a momentary decrease in FEPAH. On the other hand, tienilic acid and probenecid reduced FEPAH at uricosuric effective doses. To compare the inhibitory effects of uricosurics on urate reabsorption and PAH secretion more directly, we investigated the effects of uricosurics on the OH- gradient-dependent urate uptake in brush border membrane vesicles and the net PAH accumulation in cortical slices. The relation between the affinity of uricosuric drug for urate and PAH transporters corresponds well with the difference between the effect on FEurate and that on FEPAH. The relative affinity of AA-193 for the urate uptake is 83-fold greater than that for the PAH accumulation. These results support the assumption that, in contrast with the other uricosurics, AA-193 has a much higher affinity for urate reabsorption system than that for the common pathway of weak organic acids in rats. PMID- 1881463 TI - Effect of cyclosporin-A treatment on endotoxin-induced airway hyperreactivity in vivo and in vitro in guinea-pigs. AB - In the present study, the role of T-lymphocytes in the development of histaminergic hyperreactivity of the airways in vivo and in vitro, after intraperitoneal administration of bacterial endotoxin (1 mg/kg) to guinea-pigs was examined. Daily oral administration of the T-lymphocyte-selective immunosuppressive drug cyclosporin A (25 mg/kg) did not prevent the endotoxin induced airway hyperreactivity in vivo. Cyclosporin A treatment itself induced histaminergic hyperreactivity of guinea-pig trachea in vitro. In cyclosporin A pretreated guinea-pigs, endotoxin did not further potentiate the histaminergic responsiveness of isolated tracheal spirals. It can be concluded that T lymphocytes do not play a role in the endotoxin-induced airway hyperreactivity in vivo. Furthermore, no definite conclusion concerning the involvement of T lymphocytes in the endotoxin-induced hyperreactivity in vitro can yet be drawn. PMID- 1881464 TI - Action of the racemate and the isomers of the platelet-activating factor antagonist bepafant (WEB 2170) after oral administration to guinea-pigs and rats. AB - The aim of the present study was to clarify whether there is a difference in terms of potency and pharmacodynamic half time between the isomers and the racemate of the platelet-activating factor antagonist WEB 2170 (bepafant) after oral administration to guinea-pigs or rats. The following experiments were performed in the guinea-pig. Infusion of platelet-activating factor at 30 ng/(kg x min) for 30 min to anaesthetized guinea-pigs induced a decrease of respiratory flow and mean arterial blood pressure. Oral pretreatment with WEB 2170 or isomers, respectively, 60 min before infusion of platelet-activating factor inhibited these changes in a dose-dependent manner. The ED50s for inhibition of respiratory flow were: (-) WEB 2170 = 0.018 (0.009-0.036) mg/kg p.o; (+/-) WEB 2170 = 0.021 (0.015-0.03) mg/kg p.o.; (+) WEB 2170 = 1.55 (1.01-3.05) mg/kg p.o. Similar ED50 values were obtained for inhibition of decrease of MAP. Doses of isomers and racemate of WEB 2170 that provided almost complete protection against platelet-activating factor at 1 h after administration were chosen for determination of the duration of the protective effect after oral administration. Oral (-) WEB 2170 or (+/-) WEB 2170 showed almost identical time-response curves for inhibition (t1/2 = 14-17 h; 0.1 mg/kg p.o.) in the guinea-pig, whereas the duration of action of (+) WEB 2170 (3-6 h; 8 mg/kg) was significantly shorter. The following experiments were conducted in the rat. Oral pretreatment with WEB 2170 racemate and isomers resulted in a dose-dependent reversal of platelet activating factor-induced hypotension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881465 TI - German Society for Pharmacology and Toxicology. Abstracts of the autumn meeting. 10-14 September 1991, Berlin. PMID- 1881466 TI - Sarcoidosis presenting as large pulmonary nodules. PMID- 1881467 TI - Worrisome rash in an undergraduate. PMID- 1881468 TI - "Reach to my complaining". Patients as storytellers. PMID- 1881469 TI - Ewing's sarcoma. PMID- 1881470 TI - Nutrition and women. AB - Balance and moderation are two good words to remember about nutrition through all phases of womanhood. By eating regularly from each of the four basic food groups, varying food intake to match your level of activity and moderating your consumption of food and drink that is considered less than good for you (fat, salt, alcohol) you should be able to maintain a satisfactory weight level and, equally importantly, feel well. PMID- 1881471 TI - Lung transplantation at UNC. The first year. PMID- 1881472 TI - Primary care: the unmet national imperative. PMID- 1881473 TI - A woman's sudden allergy to all foods. The distilled water solution. PMID- 1881474 TI - Analgesic induced headache. PMID- 1881475 TI - Budget cuts affect the mentally ill. PMID- 1881476 TI - Does the public truly want national health care or do they know what they'll receive in return. PMID- 1881477 TI - The art and science of medicine. PMID- 1881478 TI - Adolescent tobacco smoking and chewing in Nebraska. PMID- 1881479 TI - "Rubeola: an atypical case". PMID- 1881480 TI - Psychosurgery: a retrospective. AB - Of the 56 patients within the Yakovlev collection who had undergone psychosurgery 11 (20%) improved, 18 (32%) were either worse or without improvement, and 27 (48%) were without any clinical follow-up. Thus, in retrospect, psychosurgery was perhaps not as successful as once envisioned. PMID- 1881481 TI - Association of trisomy 18 and hydramnios. PMID- 1881482 TI - [The tonic activity of single nerve fibers of the rabbit cervical sympathetic nerve]. AB - Spontaneous sympathetic activity was recorded in single fibres dissected from the cervical sympathetic nerve trunk (CSNT) of rabbit. Conduction velocities and action potential amplitudes for B-fibres were measured in the whole nerve trunk. Results of the spectral analysis suggested that activity of unmyelinated fibres depended on baroreceptor activity to a greater extent than that of myelinated fibres and that the 2-3 Hz rhythm was present in animals with intact baroreceptors simultaneously with the cardiac rhythm. That rhythm was a usual feature of activity of both B- and C-fibres. Cross-correlation analysis of the single fibre activity was estimated in 24 fibre pairs. It was found that in five fibre pairs there was a correlation associated with the presence of a common physiological rhythm, in one fibre pair there was a correlation derived from the existence of a strong common input to both distinct preganglionic neurons. PMID- 1881483 TI - [The periodic components of the integral tonic activity of the sympathetic nerves]. AB - Sympathetic spontaneous activity in peripheral nerves of limbs and activity of C fibres of the cervical sympathetic nerve trunk (CSNT) were recorded in situ from anaesthetized rabbits using multichannel coherent recording technique. Spectral characteristics of the activity and correlation between nerve activity and blood pressure were estimated. The data obtained have suggested that C-fibres in the CSNT are mainly vasoconstrictor fibres and their activity is more baroreceptor dependent than that of sympathetic fibres in peripheral nerves. It is found that latencies of changes in the arterial blood pressure in response to changes in sympathetic activity are between 4 and 10 s. PMID- 1881484 TI - [The comparative characteristics of the neuronal activity in surviving slices of transplanted and intact neocortex]. AB - The background single unit activity and single or multiunit responses to electrical stimulation of the rat's embryonic cortex, grafted into the somatosensory cortex of adult rats were investigated in a slice preparation. The same characteristics of the intact cortex neurons were observed as a control. The percentage of neurons with background activity within grafts was higher, than that within intact neocortex slices (23% and 6%, respectively). However the percentage of neurons responding to electrical stimulation of the recipient neocortex was lower in grafts. The mean latency of multiunit responses of graft neurons was longer, than that of neurons of the intact neocortex recorded at the same distance from the stimulating electrode (19.4 +/- 5.0 and 5.8 +/- 1.1 ms, respectively). Duration of the evoked population discharges was approximately ten times longer in grafts. It is concluded that there are local functional connections between a graft and the host brain and that inhibitory processes within grafts are weak. Functional integration of grafts with the host brain of the recipients after cranial trauma is shown. PMID- 1881485 TI - [The spontaneous synaptic activity in a cell culture of chick embryo spinal cord]. AB - Development of spontaneous synaptic activity was investigated during first 2.5 weeks in culture by means of the "hole-cell" version of the patch-clamp technique. Glycine-mediated giant postsynaptic currents (PSCs) were the most prominent property of the synaptic activity pattern. Excitatory PSCs were not observed until 14 days in culture. The role of culture conditions for the maturation of spontaneous activity has been shown. Possible mechanisms of the burst activity generation are discussed. PMID- 1881486 TI - [The retinotopic organization of the posterior suprasylvian area of the cerebral cortex in the cat]. AB - Posterior suprasylvian area (PSA) is one of the extrastriate visual structures of the cat cortex. Representation of the visual field in the PSA has been investigated by the mapping method. Results of experiments revealed that receptive fields (RF) of the PSA neurons were located mostly in the upper contralateral quadrant of the visual field. About 10% of RF were located in the upper ipsilateral quadrant of the visual field. In the upper PSA (21a, 21b) area centralis is mainly represented including the space of the radius of 20-30 degrees of the visual field. In the lower PSA (20a, 20b) more peripheral part of the visual field was represented. The experiments did not confirm essential differences in the retinotopic organization between areas 20a and 20b, 21a and 21b. Proceeding from the presented experiments the suggestion is put forward that PSA consists of two main areas (21 and 20) without dividing into subareas. PMID- 1881487 TI - [The convergence of influences from the locomotor points of the midbrain and medulla oblongata and from the inhibitory point of the pons onto the bulbar neurons]. AB - Synaptic responses of medial and lateral medullary neurons to repetitive stimulation of locomotor points (LPs) of the midbrain and medulla and of an inhibitory pontine point were recorded in mesencephalic decerebellate cats. Excitatory postsynaptic potentials (PSPs) and discharges were observed usually in medial neurons as well as mixed PSPs when an inhibitory point was stimulated. Almost a half of lateral neurons and more than a quarter of medial ones changed the frequency of the background discharge giving no responses time-locked to stimuli. Medial neurons with responses time-locked to stimuli were equally susceptible to stimuli delivered to midbrain and medullary LPs and almost as often to stimuli applied to the inhibitory point. Medial neurons with responses time-unlocked to stimuli and lateral neurons were mostly susceptible to the input from the medullary LP, less affected by stimulation of the midbrain LP and responded rarely to stimulation of the inhibitory point. Convergence of influences from the midbrain and medullary LPs was the same onto neurons of all populations. Role of different neuronal populations for initiation and cessation of locomotion is discussed. PMID- 1881488 TI - [The effect of anoxia and energy metabolism inhibitors on potassium and sodium homeostasis in the neurons of the gastropod mollusk]. AB - Anoxia and inhibitors of energy metabolism have been studied for their effect on intracellular K and Na concentrations, membrane potential, conductivity, passive and active ouabain-sensitive transport of potassium (86Rb) in neurons of freshwater snail Planorbarius corneus. The X-ray microanalysis has shown that anoxia caused no changes in K and Na concentrations in neurons. NaCN inhibited oxygen uptake by ganglia, but has actually no effect on the membrane potential, conductivity and 86Rb uptake in neurons. Much stronger inhibition of the 86Rb uptake was observed in the presence of 2-deoxy-D-glucose. When both glycolytic and respiratory inhibitors were added, the effect was maximal. It is supposed that glycolysis is the main source of energy to maintain the ion homeostasis in the mollusc neurons. PMID- 1881490 TI - [The synaptic responses of the neurons in the medulla oblongata to stimulation of the stepping stria of the spinal cord in the cat]. AB - Synaptic responses of bulbar neurons to stimulation of stepping points in the dorsolateral funiculus were recorded in decerebrate cats. 40% of neurons were excited from both ipsi- and contralateral stepping points, the rest of them were excited only from one of those points. Part of the neurons was activated from stepping points at both C2 and Th12 spinal cord levels. Latencies of the synaptic responses to stimulation of the stepping point at the cervical level were from 2 to 18 ms. These results suggest that bulbar neurons as well as propriospinal ones contribute to initiation of locomotion. PMID- 1881489 TI - [Visual illusions during the electrical stimulation of the labyrinth]. AB - Transcutaneous electrical stimulation of the labyrinth induced apparent motion of a stationary light source in darkness in normal subjects. This effect is similar to the oculogyric illusion induced by rotatory vestibular stimulation. Monaural anodal stimulation of the right labyrinth evoked apparent movement of the target to the left, whereas cathodal stimulation induced opposite illusion. The threshold current was 0.35-0.6 mA. Binaural bipolar stimuli induced illusory target motion directed to the side of the cathode, the threshold decreased 1.5 2.5 times. Binaural monopolar stimulation induced vertical apparent displacement of a target, the threshold being 1.4-3.0 mA. The amplitude and velocity of illusory target motion increased with current. The subject eyes began to move with much higher currents than those necessary for illusory sensation. It is therefore suggested that the visual illusion is related not to vestibulo-visual interaction but to vestibular effects on the spatial perception system. PMID- 1881491 TI - [The hysteretic properties of single-joint movements evoked in nonanesthetized cats by the method of microstimulation of the motor cortex]. AB - Hysteretic aftereffects in the elbow joint movements were studied on unanaesthetized cats. Flexor and extensor movements were evoked by microstimulation of the motor cortex. The cortically evoked movements were tested mechanically by applying the servo-controlled torque changes to the joint. Stiffness of the joint depended on the direction of previous movement and was significantly larger after changes in direction of movement. That led to uncertainty in the equilibrium value of the joint angle, which was demonstrated under cyclic changes of torque. PMID- 1881493 TI - [The participation of the interstitial nucleus of Cajal in initiating locomotion in cats and rats]. AB - Electrical stimulation of the interstitial nucleus of Cajal and adjacent structures elicited locomotion in cats and rats. The thresholds were 20-30 muA for decerebrate and 70-100 microA for intact narcotized animals. PMID- 1881492 TI - [The effect of microstimulation of the motor cortex on the myotatic muscle reflexes of the elbow joint in the nonanesthetized cat]. AB - Influence of the motor cortex microstimulation on the myotatic reflexes of the elbow joint muscles was studied on unanesthetized cats. The reflexes were evoked by the servo-controlled changes in torque or joint angle. Biceps and triceps muscles were usually coactivated. Microstimulation of the motor cortex against a background of an increase of the EMG activity usually suppressed the reflex responses in an agonist and had almost no influence on the reactions of an antagonist. PMID- 1881494 TI - [Load dynamics on the extremities during locomotion in rats before and after deafferentation]. AB - Stepping of an intact animal was characterized by a fast rise to maxima, maintenance on this level and fast decay of limbs' loading in the stance phase. In deafferentated rats a slow rise without maintenance in that phase was found. The role of afferent input intensity in reflex control of movements is discussed. PMID- 1881495 TI - Familial IgG subclass imbalance, anti-SS-A antibodies and third-trimester foetal death. AB - Foetal heart block occurred in the second pregnancy of an apparently healthy 23 yr-old woman. Her mother and sister were known for 10 yr with hypergammaglobulinaemia which was due to a disproportionate polyclonal elevation of serum IgG1 and with a high titre of rheumatoid factors. No associated disease was obvious. A third-trimester foetal death had occurred with each of these patients. In the sera of these three women circulating anti-SS-A (Ro) antibodies were detected, which are known to be associated with congenital heart block. IgG subclass imbalance, consisting of a disproportionate polyclonal elevation of IgG1, has been recognised as being associated with a characteristic autoantibody pattern. Familial occurrence of this syndrome as such has hitherto not been reported. PMID- 1881496 TI - Diagnostic and prognostic value of quantitative immunohistological examination of lip biopsy in Sjogren's syndrome. AB - Three patients are presented to illustrate the diagnostic and prognostic value of quantitative immunohistological examination of labial salivary gland biopsy in Sjogren's syndrome. In an obvious case of primary Sjogren's syndrome and in a case of rheumatoid arthritis without clinical and serological evidence of secondary Sjogren's syndrome, quantitative immunohistological examination of the labial salivary gland biopsy gave more appropriate information than the widely accepted lymphocytic focus score criterion for Sjogren's syndrome. In the third case quantitative immunohistological examination disclosed monoclonal B-cell expansion in the labial salivary gland biopsy six months before evidence of systemic monoclonal gammopathy appeared. PMID- 1881497 TI - Disappearance of autoantibody-induced haemolysis after excision of a malignant thymoma. AB - An 82-yr-old woman presenting with autoimmune haemolytic anaemia was found to have a malignant thymoma. A mild, largely compensated, haemolytic anaemia was observed for 5 weeks; steroid therapy was not instituted. Subsequent excision of the thymoma was followed by prompt and permanent (3-yr follow-up) disappearance of the haemolysis. To date, only two such case reports have been published. In both cases, however, the haemolysis did not abate until some months after excision of the thymoma and subsequent administration of corticosteroids. The history presented here serves to illustrate the intimate relationship between thymomas and certain autoimmune diseases. PMID- 1881498 TI - Nontuberculous mycobacterial sternal osteomyelitis in a patient without predisposing condition. AB - A woman is reported with a ten-year history of nonspecific chest pain. Bone scintigraphy showed increased local uptake, suggesting isolated sternal osteomyelitis. Radiographic investigations were positive 18 months later. Cultures of needle aspirations of the sternal bone marrow isolated Mycobacterium fortuitum as well as Mycobacterium simiae. Due to its indolent nature, nontuberculous mycobacterial disease is easily missed, especially in non compromised hosts. PMID- 1881499 TI - Paradoxical response of intracranial tuberculomas during chemotherapy: an immunologic phenomenon? AB - Intracranial tuberculomas are rare in developed countries, occurring mostly in non-Caucasian patients. We describe a white Dutch patient with miliary tuberculosis, who was noted to have intracranial tuberculomas on computed tomographic scanning. During antituberculous chemotherapy the systemic tuberculosis was responding satisfactorily, while intracranial tuberculomas developed or enlarged. Although this caused anxiety and led to some changes in chemotherapy, the lesions eventually disappeared. Possible mechanisms of this paradoxical response are discussed. PMID- 1881500 TI - Fulminant hepatic failure: to transplant or not to transplant. AB - Despite progress in intensive care regimens and the introduction of various hepatic support procedures, the survival rate for fulminant hepatic failure remained around 20%. In the past few years, orthotopic liver transplantation has increased the survival rate to more than 50% and thus is generally considered the treatment of choice. However, since about 20% of the patients on standard therapy recover spontaneously, not all patients presenting with fulminant hepatic failure should undergo transplantation immediately. Therefore attempts should be made to identify the patients with "potentially reversible" liver disease in an early phase. In this article strategies for deciding which therapy fits the individual patient are proposed. The decision "to transplant or not to transplant" should be based on residual functioning liver-cell mass (e.g. factor V is less or greater than 15%), the presence or absence of systemic complications such as lactic acidosis and renal failure and the aetiology of the liver disease (e.g. reversible causes such as viral hepatitis B and irreversible causes such as Wilson's disease). A flow diagram has been constructed. PMID- 1881501 TI - Insulin as a cause of sodium retention and hypertension. PMID- 1881503 TI - A prospective study of untunnelled subclavian vein catheters in hematooncology patients. AB - In patients with hematological malignancies, we prospectively evaluated the use of untunnelled subclavian vein catheters placed either for short term chemotherapy (48 episodes) or for long-term intensive supportive care during pancytopenia (152 episodes). The 200 catheters were placed in 88 different patients. There were 2 placement failures and 2 cases of minor pneumothorax. In 4 episodes ecchymoses and in 1 uncontrollable bleeding from the exit site occurred. The mean time to removal was 25.6 days (range 0-149). There was 1 exit site infection and 26 periods of septicemia, of which 8 were considered catheter associated. All infections responded to appropriate treatment. Irreversible obstruction occurred in 4 and dislodgement in another 4 episodes out of a total number of 11 failures. Patient acceptance was high although repeated placements were frequently undertaken for successive periods of treatment and supportive care. With meticulous sterile techniques of placement and catheter care it seems that untunnelled subclavian vein catheters are reliable and safe in hematooncology. PMID- 1881502 TI - Effects of a new effervescent cimetidine formulation on gastric acidity in healthy subjects. AB - The effect of a new effervescent formulation of 800 mg cimetidine on intragastric acidity was studied in 10 fasting healthy male volunteers. Using a randomised, cross-over design, the effect of this new cimetidine formulation was compared with that of a standard dose of a liquid aluminium/magnesium hydroxide antacid (Maalox). Intragastric pH was continuously monitored with a combination glass electrode and a digital data recorder. After a baseline period of 1 h the effect of the drugs was studied for 5 h. Both drugs increased the intragastric pH instantaneously, but the effect of Maalox ceased after 45.3 +/- 31.0 min (mean +/ SD), whereas that of effervescent cimetidine persisted for the entire 5 hr study period. Time with pH greater than 3.5, time with pH greater than 2, greater than 3, greater than 4, greater than 5 and greater than 6, and areas under the pH-time curves were significantly (P less than 0.001) higher for effervescent cimetidine than for Maalox. It is concluded that the new cimetidine formulation studied effectively combines, at least in healthy male volunteers, the immediate effect of a pH buffer with the prolonged systemic effect of an H2 blocker. PMID- 1881504 TI - Legionella pneumonia complicated by adult respiratory distress syndrome. AB - Two patients with sporadic Legionella pneumonia complicated by adult respiratory distress syndrome (ARDS) are described. Details about the clinical course and follow-up of their chest films are provided. The outcome in both patients was favourable. Literature concerning Legionella pneumonia complicated by ARDS is reviewed. PMID- 1881505 TI - Prolonged fever and pyuria: an uncommon manifestation of Q fever. AB - A patient with Q fever is described who had been ill for a year before the diagnosis was made on the basis of serological data. In addition it was possible to isolate Coxiella burnetii, the causative agent by culture from the urine. This is very exceptional and is to our knowledge only the second case in which this has been achieved. The patient made a full recovery after lengthy treatment with tetracycline. Q fever should be considered in patients with pyrexia of unknown origin, particularly in travellers. PMID- 1881506 TI - Behcet's syndrome treated with colchicine. PMID- 1881507 TI - Development of a vaccine against AIDS: state of the art. PMID- 1881508 TI - Methylprednisolone pulse therapy in rapidly progressive glomerulonephritis. AB - Twenty-five patients with rapidly progressive glomerulonephritis (RPGN) were treated with methylprednisolone (MP) pulse therapy (1 g intravenously on 3 successive days). In all patients renal biopsy was done before or just after the start of therapy. Pulse therapy was used in all patients in combination with a low oral maintenance dose of prednisone. In 21 patients additional immunosuppressive treatment was given, either cyclophosphamide (n = 19) or azathioprine (n = 2); in 2 patients plasmapheresis was also applied. Sixteen of the 25 patients were dialysis-dependent at presentation; 11 of them improved, an additional 3 had a temporary recovery, but needed maintenance renal replacement therapy after 5-46 months, mean 22 months. Nine of the 25 patients were not dialysis-dependent, 6 of them improved, an additional one had a temporary recovery, but needed chronic dialysis after 35 months. When many irreversible glomerular lesions were present, the effectiveness of MP pulse therapy was limited or only of a temporary character. Serious side effects did not occur. In conclusion MP pulse therapy is a successful treatment with minimal adverse reactions in patients with RPGN and active histological lesions. PMID- 1881509 TI - [Aneurysmal temporal bone cyst. Apropos of 2 new cases]. AB - Aneurysmal bone cyst is a well known lesion on the metaphyse of lung tubular bones or on the spine. Unusually, it is detected on the skull and more rarely again on the temporal bone. The authors, talking about the eleven cases they have found in the literature and two recent personal cases, try to describe the main diagnostic dates of this temporal lesion which one has never known if it is a real tumor or a reactional dystrophic pseudotumor secondary to an intrabone circulatory incident, perhaps a phlebitis. As for all other locations, these temporal bone forms are more frequently encountered among adolescents or young adults and, because their blowing bone effect, give clinical signs which directly result from their aggressive behavior on the surrounding structures, in this particular location: temporal fossa swelling, otologic, ophthalmologic or stomatologic symptoms, facial or trigeminal nerves troubles and rarely central neurological signs. On CT-scan, it appears as a space-occupying lesion located in the temporal fossa, with a blowing bone aspect, with intracranial and infratemporal expansions. This CT scan lesion is heterogeneous and contrast enhanced except in its center which is hypodense, as a cyst. The MRI shows comparable pictures. Its total excision, made easier by a preoperative embolization, gives a total and definitive recovery. PMID- 1881510 TI - [Treatment of chronic hydrocephalus in adults by lumboperitoneal shunt. Results and indications apropos of 82 cases]. AB - Patients with chronic hydrocephalus are most often aged people and in bad general condition. It seems that treatment may be more simplest possible and the less iatrogenic. Furthermore, the diagnosis of chronic hydrocephalus is not often certain, and can be generally assert after the good result of the CSF shunting. Since 1985, when hydrocephalus appears communicant, a lumboperitoneal shunt was systematically implanted in the aim to decrease the number of complications due to ventricular shunts. The operation can be performed on neuroloptanalgesia and/or local anesthesia. Post-operative orthostatic intracranial hypotension can be prevented by using valves with opening pressure varying with the position or valves with a flow depending of the opening pressure. Our clinical series includes 82 patients (51 males and 31 females), aged from 27 to 88 years (average 55 years). In 47 cases, hydrocephalus was idiopathic and in 35 cases hydrocephalus was secondary to an identified aetiology: subarachnoid or intracranial hemorrhage (20 cases), post-traumatic (11 cases), post meningitic (1 case) and post anoxic (1 case). In this last case, physiopathological mechanism was unclear. The middle delay between the first symptom and the operation was greater than 6 months for the majority of observations, but in few cases, precoce shunting was performed (between 1 to 3 months) in post S.A.H. and post traumatic hydrocephalus when C.T. Scan shows increasing ventricular size. Clinical results are evaluated after 2 months and at long term, and complications analysed. The lumbo-peritoneal shunt gives same results on the clinical symptoms, and less iatrogenic complications than ventricular shunts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881511 TI - [Vertebro-dural arteriovenous fistulae of the foramen magnum with perimedullary venous drainage]. AB - Two cases of dural arteriovenous fistulae of the foramen magnum with perimedullary venous drainage are reported. Their arterial component was a dural branch of a vertebral artery. The localization and the origin of these fistulae appeared very uncommon but could be explained by the embryogenesis of the vertebral arteries, of which the third portion corresponds to the first cervical radicular artery. The first patient had signs and symptoms usually described in this disease, but the second presented a subarachnoid haemorrhage with neither motor and sensory deficit not sphincter disturbance. Myelographic findings, M.R.I. abnormalities and treatment of these rare dural arteriovenous malformations are discussed. PMID- 1881512 TI - [Emergency preoperative embolization using coils of ruptured sylvian aneurysm. Apropos of a case]. AB - The authors report a case of a 73 year old patient who presented with a right temporal lobe hematoma secondary to rupture of a right middle cerebral artery bifurcation aneurysm. Treatment consisted of partial thrombosis of the aneurysm by the endovascular introduction of metallic coils followed by surgical hematoma evacuation and aneurysm clipping. Thrombus of the aneurysm done probably diminished the risk of intraoperative rupture. Partial endovascular treatment has a very small risk and may be done on a emergency basis at the same time as the diagnostic arteriogram. It can also be suggested for patients in poor condition to diminish the risk of recurrent hemorrhage until the patient is well enough to undergo definitive surgical clipping. PMID- 1881513 TI - [Intra-orbital hydatid cyst. An uncommon site of hydatidosis. Discussion apropos of a recent case]. AB - The authors present an observation of intraorbital hydatid cyst. They review the literature and discuss the main data of such a rare lesion. Hydatid cyst should be systematically evoked in any case of tumoral exophthalmia developed in a young patient, particularly if he comes from an endemic country. The pre-operative diagnosis relies on the confrontation between clinical and echographical data, and C.T.-scan imaging. The only treatment is surgery. A puncture performed at the beginning of the surgical procedure will confirm the diagnosis. In fact, it should be indicated for every intra-orbital neoplasm observed in a country of endemicity, mostly when the preoperative diagnosis is difficult, that is when no C.T.-scan or echography are at disposal. The infectious prognosis is excellent; but the functional one depends on the precocity of surgery and remains reserved in most cases. PMID- 1881514 TI - Genotype differences in catecholamine concentrations in hypothalamus, intramedial hyperstriatum ventrale, and optic tectum of newly hatched chicks. AB - This study was designed to compare catecholamine concentrations among three brain areas of four pureline populations of visually isolated chicks. The purelines used were a commercial male line, a fertility selected line, an unselected fertility control line, and unselected White Jersey Giants. In general, male chicks had significantly larger brain weights than females. Six catecholamine related compounds (norepinephrine, epinephrine, L-DOPA, dopamine, DOPAC, and MHPG) were measured via HPLC-ECD. No significant differences in neurochemical concentration were observed for any line or brain area due to sex of the chick. The hypothalamus (HT) contained the greatest concentration of catecholamines in all lines, followed by the intramedial hyperstriatum ventrale (IMHV) and optic tectum (OT). The HT exhibited consistent lateralization in all lines with the right HT containing ca. 30% more catecholamines than the left HT. While no consistent lateralization was observed among the other brain areas, the IMHV exhibited significantly different degrees of lateralization among the populations. Neuronal activity, as measured by MHPG:NE and DOPAC:DA ratio varied by line within each brain area. There were line differences for MHPG:NE in the HT, IMHV, and OT, while line differences for DOPAC:DA were observed in the HT. Since differences among purelines have been demonstrated in this study, care must be given to precisely define the genotype of chicks used in behavioral and neurochemical research. PMID- 1881517 TI - The thirty-third annual meeting of the Japanese Neurochemical Society. Hiroshima City, October 24-26, 1990. Abstracts. PMID- 1881515 TI - The phylogenic expression of plasmolipin in the vertebrate nervous system. AB - Plasmolipin is a plasma membrane proteolipid is a major myelin membrane component (Cochary et al., 1990). In this study we report the phylogenic expression of plasmolipin in the vertebrate nervous system. Using Western blot analysis with polyclonal antibodies, we have analyzed membrane fractions, including myelin, from elasmobranchs, teleosts, amphibians, reptiles, birds and mammals. On the basis of immune detection, plasmolipin appears to be restricted to the mammalian nervous system. Comparison of the central and peripheral nervous systems of mammals showed only minor differences in the level of plasmolipin in these two regions. Within mammals, little quantitative differences were observed when rat, human and bovine membrane fractions were compared. The late evolutionary expression of plasmolipin which results in its restriction to mammals makes it unique among the (major) myelin proteins. The potential physiologic significance of these data are discussed. PMID- 1881518 TI - [Neurovascular cross-compression as a cause of severe vertigo and surgical treatment]. PMID- 1881516 TI - GABA synthesis in brain slices is dependent on glutamine produced in astrocytes. AB - The rate of gamma-aminobutyric acid (GABA) synthesis in rat-brain slices was determined by inhibiting GABA transaminase with 20-microM gabaculine and measuring the increase of GABA. Added 500-microM glutamine increased the rate of GABA synthesis by 50%, indicating that glutamate decarboxylase is not saturated in brain slices. The stimulation of GABA synthesis with added glutamine in brain slices was much less than that reported for synaptosomes. The lower stimulation in slices was attributable to astrocytic glutamine production, as the rate of GABA synthesis decreased by 44% when glutamine production was inhibited with methionine sulfoximine. Added glutamine restored the rate to the maximal value observed in brain slices. The rate of GABA synthesis was decreased by 65% in slices pretreated with an inhibitor of glutaminase, and added glutamine did not reverse this effect. These results suggest that glutamine produced by astrocytes is a quantitatively important precursor of GABA synthesis in cortical slices. PMID- 1881519 TI - [Intraoperative lumbar injection of Ringer's solution for surgical treatment of chronic subdural hematomas]. AB - A series of 64 patients underwent surgical treatment for chronic subdural hematomas between 1980 and 1989. The procedure consisted of a single burr-hole, irrigation of the hematoma without subdural drainage and lumbar intrathecal injection of Ringer's solution. Irrigation was carried out until the washing was clear and the injection was continued until the brain was in contact with the edge of the burr-hole. Excellent outcome was achieved in 53 patients (82.8% of the total). Two of the patients died, thus making a 3.1% mortality rate. Such complications as tension pneumocephalus and intracerebral hematoma were not observed and no patient had a recurrence. PMID- 1881520 TI - [Clinicopathological study of meningiomas of the tentorium and its surrounding structures]. AB - We report the clinical features, radiological studies, operative procedures and results, and follow-up data in 29 patients with meningiomas of the tentorium and its surrounding structures. The cases represented 22.5% of all the intracranial meningiomas operated on in a 15 year period and were divided into three groups, depending on their main attachments, tentorial, cerebellopontine angle (dorsal aspect of the petrous ridge) and others. Tumor size was generally large and 13 cases were larger than 5 cm. The most common tumor site was along or near the superior petrosal sinus and transverse-sigmoid junction in cases involving the tentorium, and medial to the porus acousticus in cases involving the cerebellopontine angle. Different operative approaches to these tumors were carried out, depending on their location. The tumors in the lateral or medial petrous ridge were approached mainly with a suboccipital craniectomy using a retromastoid incision. Total removal was carried out in 80% of the tentorial cases, in 46.2% of cerebellopontine angle cases, and in the 83.3% in the others. Total operative mortality rate was zero. Follow-up periods ranged up to 5 years 5 months in the tentorial cases, 4 years 6 months in cerebellopontine angle cases, and 7 years 1 month in the others. Long-term results were good in 21 cases (72.4%), fair in 3 cases (10.3%) and poor in 2 (6.9%). Three patients died due to tumor recurrence. One of them suffered lung metastasis, and two of them suffered extensive local recurrences. We recommend the retromastoid approach combined with the petrosal approach, if the CPA tumor is large enough and extends to the retroclival region. PMID- 1881521 TI - [Treatment for serious cases of ruptured intracranial aneurysms with severe subarachnoid clot]. AB - Forty-one serious cases of ruptured intracranial aneurysms with severe subarachnoid clot were clinically analyzed, with special emphasis on the prognosis, pathophysiology, and surgical indications. All cases had thick subarachnoid clot without concurrent intracerebral hematoma and/or intraventricular hematoma causing mass signs on the CT scan. In this series, 23 cases underwent radical surgery while in the acute stage, 18 cases were treated conservatively (including 5 cases treated only by continuous ventricular drainage). The criterion for determining the degree of severity was defined as either a "semicoma" or "coma" state just prior to radical surgery for the radically-operated group, with the same designations for the conservative group at their time of admission. All patients except two in the conservatively-treated group died due to primary brain damage caused by massive subarachnoid hemorrhage. The two remaining cases died from other complications. On the other hand, the outcome for the 23 surgically-treated patients was as follows: Three (13%) fully recovered; three (13%) were capable of self-management; eight (34.8%) were partially or fully dependent. Nine (39.1%), died. In the radically-treated group, pre-operative factors that might predict clinical outcome were investigated. Those factors were the neurological grade, the brain-stem response, the response after the rapid administration of 20% Mannitol (300-900 ml), and the length of time from the last bleeding episode to the time that radical surgery was performed. It was recognized that there was no relationship between the neurological grade just prior to radical surgery and the outcomes in the serious cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881522 TI - [Effect of X-rays combined with ACNU and O6-ethylguanine on rat subcutaneous gliomas]. AB - Rat gliomas of subcutaneously transplanted RGc-6 cells were irradiated with X-ray either alone, or combined with ACNU, and the cell-survival was assayed in vitro. Cell-survival curve composed of two components by X-irradiation alone indicated the presence of a hypoxic cell fraction. We have previously shown that combined treatment with ACNU apparently made the effect of X-ray on spheroids in vitro of the same cell line of RGc-6 more powerful. Although treatment of rat gliomas with ACNU administered at 2 hrs prior to X-irradiation was most effective, it resulted in only the additive effect of the independent action of the two agents. Further treatment by O6-ethylguanine prior to ACNU administration and X-irradiation apparently increased the strength of the effect of ACNU combined with X-ray to the dose-modifying factor for X-ray of 1.8. The result indicated that the combination of O6-ethylguanine prior to ACNU administration and X-irradiation may clinically enhance the effect of X-ray against apparent ACNU-resistant glioma cells such as RGc-6 cells. PMID- 1881523 TI - [Efficacy and some complications of programmable pressure valve]. AB - Twenty-five patients with hydrocephalus were treated using Sophy programmable pressure valve. The valve pressure is adjustable percutaneously with a magnet. This valve was very useful for management cases presenting overdrainage and high risk cases of shunt dysfunction such as aqueductal stenosis and idiopathic normal pressure hydrocephalus. It was also useful for hydrocephalus after subarachnoid hemorrhage because it was difficult to know the most adequate pressure before the shunt operation. Two patients developed acute subdural hematoma of arterial origin after the shunt operation. The causative factor appeared to be low intracranial pressure and rupture of small arterial branches. This complication may be more frequent in cases using this system than in cases using other systems. We must pay attention to this complication and it is necessary to improve the shunt system. One bed-ridden patient developed necrosis of the skin because of this valve, and it had to be removed. We should place this valve so that it is at the anterior of the chest. PMID- 1881524 TI - [Persistent primitive proatlantal intersegmental artery (PPPIA) presenting with cerebral infarction]. AB - A case of persistent primitive proatlantal intersegmental artery (PPPIA) is reported. A 65-year-old male with treated hypertension was admitted to our clinic complaining of dysarthria and hemiparesis of sudden onset two days after the ictus. CT revealed spotty low-density lesions in the left corona radiata and bilateral thalami with bilateral watershed infarction. MRI findings were also compatible with cerebral infarction. Left common carotid angiography demonstrated a large anastomosis between the external carotid artery and the vertebral artery at the proatlantal region. Neither of the vertebral arteries were visualized on digital subtraction aortography. All the blood circulation of the vertebro basilar system was through this anastomotic artery (PPPIA). A flow study revealed hypoperfusion in the territory of the left middle cerebral artery on 133Xe SPECT. Bone window CT of cervical vertebrae revealed hypoplasia of the left transverse foramen in C2, C3, C4, C5, C6 vertebrae. This case is very suggestive of an anaplasia or hypoplasia of the vertebral arteries. The etiology of his left frontal infarction seemed to be a blood-stealing phenomenon of long standing, from the anterior to the posterior circulation through the PPPIA. PMID- 1881525 TI - [P3 portion aneurysm of the posterior cerebral artery; a case report]. AB - A case was reported of surgically treated saccular aneurysm located at the right posterior temporoparietooccipital artery junction (P3 portion of PCA). An aneurysm of this portion is said to be rare, and only 7 cases have been described so far. A 74-year-old female was transferred to our clinic, after 3, 5 months of sustaining aneurysmal rupture, for surgical treatment. The patient had been treated conservatively because of her severe condition in the early stage. She was in nearly apallic state with left hemiparesis at the time of admission to our clinic. During the acute stage of her illness, moderate hematoma in the right ambient cistern without hydrocephalus, and an aneurysm at P3 portion of the right posterior cerebral artery with marked arteriosclerosis were delineated by CT, and by right vertebral angiography respectively. However, in the CT taken 3, 5 months after the onset, moderate hydrocephalus and a low density area in the right internal capsule were detected. Aneurysmal neck clipping was performed using the right posterior subtemporal approach, without any deformity of the parent arteries. Occlusion of the right parietooccipital artery occurred, however, probably on the 2nd postoperative day. Despite the newly developed left homonymous hemianopsia, general condition, including consciousness level, improved postoperatively particularly after the ventriculo-peritoneal shunt was carried out. PMID- 1881526 TI - [Vertebral dissecting aneurysm treated with trapping and bilateral posterior inferior cerebellar artery side-to side anastomosis; case report]. AB - A case is reported of ruptured dissecting aneurysm of the intracranial vertebral artery (VA) operated on with VA trapping and bilateral posterior inferior cerebellar artery (PICA) side-to-side anastomosis. A 42-year-old male suddenly developed severe headache and vomiting. On admission, 3 hours later, he was in a state of moderate confusion (Japan Coma Scale 3) and had neck stiffness. Computed tomography (CT) revealed diffuse subarachnoid hemorrhage, especially thick in the posterior fossa with right side dominance. Right vertebral angiography disclosed a fusiform dilatation with proximal narrowing of the right VA which originated just proximal to the VA-PICA junction. Lateral suboccipital craniectomy was undertaken with the patient in a left park bench position. Right VA was dilated and discolored black, and right PICA arose from the proximal portion of this aneurysmal dilatation. Since it was impossible to clip the VA distal to the PICA for the proximal clip-occlusion, the VA including the VA-PICA junction was trapped. Considering the risk of developing infarction at the PICA territory, bilateral PICA was anastomosed at their posterior medullary segment in a side-to side fashion because the occipital artery (OA) had been cut at the skin incision and could not be used for the OA-PICA anastomosis. The postoperative course was benign, but a mild lateral medullary syndrome developed. CT revealed no abnormal low density area and left vertebral angiography demonstrated the patency of the bypass. Thereafter, the deficit subsided gradually and the patient was discharged. He is presently working without neurological deficit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881527 TI - [A case of successfully removed posttraumatic high flow dural arteriovenous fistula in the posterior fossa]. AB - A 49-year-old male patient was admitted to Ryukyu University Hospital complaining chiefly of progressive loss of mental activity for one year. He had a history of head trauma at the right retromastoid region when he was 24. Generalized convulsions developed three years later, and left exophthalmos, facial varix and impairment of visual acuity developed seven years later. Dural arteriovenous fistula of the posterior fossa was diagnosed at the age of 32, and feeding EC and tentorial arteries were successively ligated on the right several times without any effect. Angiography during this admission revealed tremendous collateral flows; a marked dilated tortuous occipital artery fed from the right vertebral artery, meningeal branches of VA and PICA, the marginal tentorial artery, and the posterior temporal artery from MCA, PCA were drained into the right transverse sinus. But transverse sinuses were occluded bilaterally, and venous outflows were directed to the superior sagittal sinus retrograde via the ascending cortical vein, Trolard veins, and sphenoparietal and cavernous sinuses. The final drainer was the superior ophthalmic vein on the left. Normal deep veins were not visible. In park bench position, the nidus was totally resected with a part of the transverse and thrombosed sigmoid sinus. Postoperative course was uneventful, and an angiogram showed complete disappearance of the AVF. Dural AVG in the posterior fossa with characteristics such as high flow, and which is rich in collaterals following palliative treatment indicates that total surgical resection should be undertaken. PMID- 1881528 TI - [A case report of adjacent tumor of sphenoid ridge meningioma and GH producing pituitary adenoma]. AB - A case of sphenoid ridge meningioma and pituitary adenoma adjacent in the brain is reported. A 70-year-old female was admitted to our hospital with headache. She had no neurological deficit but did have acromegalic change. Hormonal examination showed elevation of plasma levels of HGH (19.0 ng/ml), with normal levels of the other hormones. CT examination revealed a tumor with calcification in the inner third of the sphenoid ridge and another in the pituitary fossa with suprasellar expansion. MRI showed flow void of ICA between these tumors. Intensity of the T1 weighted image of the tumor in the sphenoid ridge was homogeneously iso intensity, and low intensity in the pituitary fossa. The diagnosis of adjacent tumors in the sphenoid ridge meningioma and pituitary adenoma had been made preoperatively. Left front-temporal craniotomy and removal of these tumors were performed. These tumors were close to each other, but were separated by the internal carotid artery and anterior cerebral artery. Pathological examination demonstrated meningotheliomatous meningioma in the sphenoid ridge and sparsely granulated somatotroph adenoma in the pituitary fossa. Fourteen cases showing association of meningioma and pituitary adenoma, which had no history of radiation and trauma, have been reported previously. Although GH producing pituitary adenoma may stimulate adjacent dura and arachnoid cells resulting in the formation of meningioma, the possibility of coincidental occurrence of the two tumors cannot be ignored. PMID- 1881529 TI - [A case of C2 neurinoma suffering syncopal episodes]. AB - A 32-year-old male had a 4-year history of episodes of loss of consciousness. These episodes occurred several seconds after he would turn his head 60 degrees to the left, and had increased in frequency at the time previous to the operation he underwent. MRI revealed a round mass on the right side between the atlas and the axis. Cerebral angiography demonstrated that the right vertebral artery (VA) was occluded at the transverse foramen of the axis with the head rotated toward the left. The left VA was hypoplastic and no posterior communicating artery was visualized. A lateral surgical approach was performed between the left sternocleidomastoid muscle and the internal jugular vein. A yellowish and elastic but hard tumor was found to compress the VA. Postoperative MRI and vertebral angiography revealed neither residual tumor nor stenosis. Although the VA is frequently compressed by cervical tumors, only a few cases have been reported with tumors whose initial symptom was vertebro-basilar insufficiency. On the other hand, symptomatic stenotic change in the VA due to head movement can occur at the atlanto-axial joint and is named "bow hunter's stroke". In this case, flow of the VA was measured with an ultrasonic flowmeter after the tumor was removed. As the flow proved to change little during head rotation, additional decompression procedures such as removal of the transverse processes were judged unnecessary. Intraoperative arterial flow measurement has been found to be quite useful for evaluating the actual effect of surgical procedures. PMID- 1881530 TI - Molecular graphics applied to 5-HT3 ligands. AB - The recent surge of scientific interest in 5-hydroxytryptamine3 (5-HT3) receptors can be attributed largely to the rapid increase in the number of potent and selective 5-HT3 receptor antagonists. The availability of a large variety of chemically diverse 5-HT3 compounds allows for a unique opportunity to apply computer-based modelling techniques to the analysis of the 5-HT3 receptor pharmacophore. The present review summarises recent studies performed in this laboratory. The primary goal of these studies was to elucidate the chemical requirements needed for molecular recognition at the 5-HT3 receptor binding site. A secondary goal was to determine if this type of molecular information could be assessed using computerised chemical databases. PMID- 1881532 TI - Functional role of brain CCK receptors. PMID- 1881531 TI - Distribution patterns of CCK and CCK mRNA in some neuronal and non-neuronal tissues. AB - Mutt and Jorpes (49) originally isolated cholecystokinin (CCK) from porcine intestine. Subsequently, it was recognized that CCK/gastrin-like material could be found in the rat brain (74), and it was later shown mainly to represent the C terminal octapeptide (CCK-8) (2, 12-14, 48, 54, 55). These radioimmunoassay studies have been supplemented by numerous immunohistochemical investigations showing extensive CCK immunoreactive neuron systems in the brain and spinal cord (20, 26, 27, 31, 37, 40, 42, 44, 72, 75, 76). During recent years several groups have employed in situ hybridisation and radioactively labelled probes complementary to CCK mRNA and partly confirmed results from immunohistochemical studies but also revealed new interesting findings (3, 5, 6, 30, 41, 58, 64-66, 77). Several lines of evidence indicate that CCK-8 may act as a neurotransmitter or neuromodulator in many areas of the central nervous system. The development of new CCK antagonists has opened up new possibilities to understand the functional significance of CCK peptides in the neurons and other systems. The aim of the present article is to briefly review the distribution of some of the CCK systems and in this way define possible targets for these new types of drugs. Focus will be on cerebral cortex in view of the theme of the meeting, anxiety, on spinal cord as a basis for discussion of CCK and pain, and finally CCK/gastrin peptides in sperm will be discussed. The question of coexistence of CCK and dopamine in mesencephalic neurons is reviewed in a parallel article (28). PMID- 1881533 TI - Development of CCK-B antagonists. AB - Our approach to design small molecule non-peptide analogues of the neuropeptide cholecystokinin (CCK) has led to the discovery of the CCK-B antagonist 'dipeptoids'. A representative member of this series of compounds, PD134308 [R (R*,R*)]-4-[[2-[[3-(1H-Indol-3-yl)-2-methyl-1-oxo-2- [[(tricyclo[3.3.1.1(3,7)]dec 2-yloxy)carbonyl]amino]propyl] amino]-1-phenylethyl]amino]-4-oxobutanoic acid has high affinity (Ki = 1.7 nM) and selectivity for the CCK-B receptor (CCK-A/B ratio is 2500:1), is well absorbed and shows robust anxiolytic properties in several anxiogenic models in a dose related manner by both s.c. and oral routes of administration over the dose range 0.1-30 mg/Kg. The rational design of these dipeptoids from CCK 26-33 has involved the identification of the non-contiguous dipeptide fragment of CCK, Boc-Trp-Phe-NH2 with low micromolar affinity in binding assays. This dipeptide has been systematically chemically modified at the N- and C-terminal to increase CCK-B binding affinity 10,000-fold. These modifications include replacement of the L-tryptophan moiety by the non genetically coded D-alpha-methyltryptophan residue. The modifications also enhance the stability of the molecule towards enzymatic and acid degradation and increase overall lipophilicity compared with the peptide in order to facilitate penetration of the blood-brain barrier. PMID- 1881534 TI - Percutaneous reposition of dislodged coils in the treatment of a vertebral arteriovenous fistula--with CT follow-up. AB - We report a case of vertebral arteriovenous fistula in which embolization was complicated by migration of two coils and a partially inflated balloon. In order to relieve compression to the spinal cord, the displaced balloon was punctured percutaneously. For both relieving compression to the spinal cord and obliterating the residual fistula, the dislodged coils in the partially thrombosed epidural venous sinus were removed percutaneously and placed in the fistula, and more coils were implanted in the fistula percutaneously through the needle. CT follow-up half a year later showed complete resolution of compression of the spinal cord and complete recovery from myelopathy was clinically apparent. PMID- 1881535 TI - Extended use of cranial CT in the evaluation of patients with stroke and transient ischaemic attacks. AB - The hypothesis was explored that patterns of ischaemic brain damage shown by CT may be of greater value in estimating the relevance of angiographic stenosis in the carotico-vertebral arteries in some patients than presenting clinical features. Five angiographic and six CT abnormalities were defined and charted independently in a blinded manner in 312 patients whom clinical features and subsequent management were known. Charts were combined for statistical analysis. Statistically significant associations were found between two types of CT lesion and angiographic abnormalities, but these were present in only 18% of cases. The distribution of clinical features did not differ significantly within this subset compared to the whole population, from which it was concluded that the hypothesis was upheld. Furthermore significantly more patients in this subset were subjected to carotid endarterectomy, suggesting that management decisions may have been modulated by CT findings in some patients. PMID- 1881536 TI - Hyperdense middle cerebral artery CT sign. Comparison with angiography in the acute phase of ischemic supratentorial infarction. AB - The early CT finding of an hyperdensity of a portion of the middle cerebral artery Hyperdense Middle Cerebral Artery Sign (HMCAS), in patients with supratentorial stroke, is often indicative of an embolic occlusion. Aim of this study was to verify the incidence and reliability of the HMCAS and its possible correlation with early CT findings and with the extent of late brain damage. We studied 36 patients presenting with symptoms of stroke in the MCA territory, by means of CT and angiography performed respectively within 4 and 6 hours. Follow up CT scans were then obtained after one week and three months from the ischemic event. The HMCAS was present in 50% of our patients and in this group it always correlated positively with the angiographic finding of occlusion. The same group presented a high incidence of early CT hypodensity (88%). Finally the presence of HMCAS might be considered a negative prognostic sign for the development of extensive brain damage. PMID- 1881537 TI - Sex and side differences of cerebral arterial caliber. AB - The diameter of 261 middle cerebral and 225 anterior cerebral arteries was measured on half axial antero-posterior (ap) view, and the diameter of 217 internal carotid arteries on side view angiograms. Mean diameter was significantly larger by 9.3%, 8.8% and 9.7% respectively in males than in females. In the females the vessels of the left hemisphere were wider but not significantly so than those of the right hemisphere, and the contrary was true for the males. In both sexes the side difference was reversed in the eighth decennium. There was no correlation of vessel diameter with age except for a statistically significant increase by 7.8% of right middle cerebral artery diameter in males from the fifth to the sixth decennium. PMID- 1881538 TI - The effect of EC-IC bypass surgery on resting cerebral blood flow and cerebrovascular reserve capacity studied with stable XE-CT and acetazolamide test. AB - Cerebral blood flow (CBF) and cerebrovascular reserve capacity (CRC) were measured by stable xenon computerized tomography (Xe-CT) and acetazolamide test in 15 patients with cerebrovascular disease before and after extracranial intracranial (EC-IC) bypass surgery for minor stroke, reversible ischemic neurological deficit or transient ischemic attack. All had angiographically shown occlusive lesions of the major arterial trunk. In the present series, global analysis showed that the bypass did not increase the resting rCBF, but did increase the rCRC. We divided the patients into four groups according to the preoperative resting rCBF and rCRC. All 3 patients with normal resting rCBF and reduced rCRC showed postoperative improvement of rCRC. Of 6 patients with reduced CBF and reduced CRC, three had postoperative increase in resting CBF and four had increased CRC. One of two patients with reduced CBF and normal CRC showed only an increase in CRC. We propose that reduced CRC or reduced CBF with reduced CRC are criteria for selection of candidates for bypass surgery. We conclude that Xe-CT with the Diamox test is a useful and simple method for evaluating cerebral hemodynamics. Preoperative grouping with a combination of preoperative resting rCBF and preoperative rCRC is useful for predicting the effect of EC-IC bypass surgery. PMID- 1881539 TI - MR imaging of intracranial hemorrhage in neonates and infants at 2.35 Tesla. AB - The variations of the relative signal intensity and the time dependent changing contrast of intracranial hemorrhages on high-field spin-echo magnetic resonance images (MRI) were studied in 28 pediatric patients. For T1-weighted images, a repetition time (TR) of 500 ms and an echo time (TE) of 30 or 23 ms was used. The corresponding times for T2-weighted images were TR 3000 ms and TE 120 ms. Intracranial hematomas, less than 3 days old, were iso- to mildly hypointense on short TR/TE scans and markedly hypointense on long TR/TE scans (acute stage). In the following four days the signal of the hematomas became hyperintense on short TR/TE scans, beginning in the periphery and proceeding towards the center. On long TR/TE scans the signal remained markedly hypointense (early subacute stage). 7-14 days old hematomas were of high signal intensity on short TR/TE scans. On long TR/TE scans they appeared hypointense in the center and hyperintense in the periphery (late subacute stage). By the end of the second week the hematomas were of high signal intensity on all pulse sequences (chronic stage). Chronic hematomas were surrounded by a parenchymal rim of hypointensity on long TR/TE scans. 28 neonates and infants (with 11 follow-up examinations) of 31.5-70.6 weeks postconceptional age (PCA), with an intracranial hemorrhage were examined. The etiologies of the hemorrhages were: asphyxia (17 cases), brain infarct (2), thrombocytopenia (1), clotting disorder (1) and unknown origin (7). The aim of this study was to describe the appearance of intracranial hemorrhages in neonates and infants with MRI at 2.35 Tesla using spine-cho sequences. PMID- 1881540 TI - Neuroimaging in lissencephaly type I. AB - The CT scan's of 22 patients with lissencephaly type I, a severe developmental disorder of the cerebral cortex, were studied. In 6 patients a magnetic resonance (MR), scan was also performed. The CT and MR scans of the lissencephaly patients were compared to a control group consisting of 49 patients with a normal CT or MR scan. In lissencephaly the cortical thickness was always larger than 10 mm, as compared to less than 7 mm in the normal situation. In lissencephaly the WSF/DSF index (with/depth of the sylvian fissure) was always larger than 0.29, while in the normal situation less than 0.25. PMID- 1881541 TI - Deep venous drainage in great cerebral vein (vein of Galen) absence and malformations. AB - We report two types of venous patterns associated with great cerebral vein (vein of Galen) absence or unavailability. Developmental venous anomalies or vein of Galen arteriovenous malformations (VGAM) serve as an illustrative material. A diencephalic pattern that collects the thalamo-striate veins into the tentorial sinus is recognized in most VGAM. A telencephalic arrangement connecting the striate veins with the rostral afferents to the basal vein is less frequent. Both patterns reproduce embryonic stages preceding the development of the great cerebral vein, thus confirming Raybaud's hypothesis that in VGAM the pouch is not the vein of Galen but the medial vein of the prosencephalon. The prognostic value of each pattern can then be appreciated and the therapeutic strategies rationalized; some unexplained complications of the venous approach for non selected VGAM can thus be avoided. PMID- 1881542 TI - A simple technique for head repositioning in CT scanning. AB - With conventional CT scans, alterations of morphology on repeated examinations can only be appreciated if significant, because identical slice positions are impossible to achieve. The authors have developed a simple and accurate method of repositioning the head not requiring conventional stereotactic head fixation and suitable for the outpatient situation. PMID- 1881543 TI - Intradiploic meningiomas. A radiological study of two cases confirmed histologically. AB - Approximately 1% of meningiomas arise in extradural sites. Intradiploic meningiomas form only a very small proportion of this number. They tend to occur in young patients. The CT and MRI appearances, although unusual, may be characteristic of the condition. We present two cases and describe the CT and MR appearance; the latter has not previously been described. PMID- 1881545 TI - Delayed epidural hematoma. AB - A case of delayed epidural hematoma is described who had an initial computerized tomography (CT) scan reported as normal. Repeat CT scan at 48 h demonstrated a right temporal epidural hematoma. A skull fracture was not observed radiographically or at surgery. The world literature is reviewed and the criteria for repeat CT scanning is discussed. PMID- 1881544 TI - Intrafrontal sinus primary meningioma. PMID- 1881547 TI - Intracranial arachnoid cysts in myotonic dystrophy. AB - Clinically apparent brain dysfunction is common in myotonic dystrophy. In a sample of fourteen adult patients with the definite form of this disease, brain magnetic resonance imaging detected frequent white matter abnormalities and ventriculomegaly. In addition, two patients exhibited an intracranial arachnoid cyst, a condition of neurosurgical interest that could be related to the generalized dysmaturational process present in this disease. Patients with myotonic dystrophy deserve a careful screening for brain involvement. Further MRI studies should ascertain the actual prevalence of brain anomalies in myotonic dystrophy and define the role of this procedure in the workup of this disease. PMID- 1881546 TI - Dense epidermoid cyst of the cerebellopontine angle. AB - A case of epidermoid cyst in the cerebellopontine angle which appeared as a hyperdense mass on CT is presented with clinical and radiological features. The preoperative tentative diagnosis proved erroneous. The literature is reviewed on this exceptionally rare radiological finding of epidermoid cysts and highlights of preoperative diagnosis are discussed. PMID- 1881549 TI - CT and MR imaging of CNS lymphomatoid granulomatosis. AB - The clinical CT and MR imaging features of a pathologically confirmed case of lymphomatoid granulomatosis are presented. The disease was clinically confined to the central nervous system and the diagnosis was only made after brain biopsy had been performed. MR imaging revealed extensive non-confluent regions of white matter abnormality. Although uncommon, lymphomatoid granulomatosis should be included in the differential diagnosis of causes of periventricular and deep white matter lesions, even in the absence of pulmonary lesions. Specific therapy may produce clinical regression of disease. PMID- 1881548 TI - MRI of subarachnoid dissemination of medulloblastoma. AB - We report two cases with subarachnoid dissemination of medulloblastoma depicted clearly by Gadolinium-DTPA enhanced MRI. We also demonstrate the superiority of Gadolinium-DTPA enhanced MRI over nonenhanced MRI, CT, myelography and postmyelographic CT for diagnosing subarachnoid dissemination and for monitoring the response to therapy. PMID- 1881550 TI - Magnetic resonance imaging in familial central diabetes insipidus. AB - More detailed examinations of the pituitary gland in central diabetes insipidus (CDI) has been possible with magnetic resonance imaging (MRI). Compared to the high signal findings in the posterior lobes of normal subjects, the absence of such signal in adults and children with primary CDI has been reported. Familial CDI is a hereditary form of primary CDI with a variety of clinical expressions among affected individuals which is said to be related to varying degrees of an arginine vasopressin (AVP) deficiency. However, the structural correlates have yet to be documented by MRI technique. This report describes the pituitary gland MRI findings (using a superconducting magnet; 3 mm-slice thickness; spinecho, repetition time 400 ms, echo time 25 ms) in five patients in one family with familial CDI. A signal of high intensity was detected in the posterior part of the pituitary gland in 2 patients but not in 3 others. We concluded that MRI of the posterior pituitary lobe in familial CDI seem to vary in members of the same family. PMID- 1881552 TI - Gadolinium-DTPA MRI in the diagnosis of a patient with leptomeningeal metastasis produced by uvular carcinoma. AB - A patient with uvular cancer presented with lower limb weakness and paresthesiae, headache, neck stiffness and multiple cranial palsies. No malignant cells were found on lumbar puncture. CT, and MRI were normal. Gadolinium-DTPA MRI disclosed multiple enhancing lesions consistent with leptomeningeal metastases. Gd-DTPA MRI is the best technique to demonstrate tumoral meningeal infiltration in cytology negative patients suspected of having leptomeningeal metastases. PMID- 1881551 TI - Brain SPECT imaging in temporal lobe epilepsy. AB - Temporal lobe epilepsy is diagnosed by clinical symptoms and signs and by localization of an epileptogenic focus. A brain SPECT study of two patients with temporal lobe epilepsy, using 99mTc-HMPAO, was used to demonstrate a perfusion abnormality in the temporal lobe, while brain CT and MRI were non-contributory. The electroencephalogram, though abnormal, did not localize the diseased area. The potential role of the SPECT study in diagnosis and localization of temporal lobe epilepsy is discussed. PMID- 1881553 TI - Radiation myelopathy: significance of gadolinium-DTPA enhancement in the diagnosis. AB - We described two cases of chronic progressive radiation myelopathy (CPRM), in which magnetic resonance imaging (MRI) was of great value for the diagnosis. Gadolinium-DTPA (Gd-DTPA) enhancement delineated precise lesions responsible for Brown-Sequard syndrome caused by CPRM in both cases. This safe, sensitive procedure will be a requisite study in patients who are suspected of CPRM. PMID- 1881554 TI - Laryngeal edema, following the injection of iohexol into the subarachnoid space. PMID- 1881555 TI - [Syncope due to sinus arrest secondary to marked vagal hypertonus. The role of permanent atrial stimulation in revealing associated atrioventricular node involvement]. AB - The authors report a case of a 42-year-old man, with relapsing syncope, related to sinus arrest, documented by Holter recording. The clinical investigation, the electrophysiological study with autonomic blockade included, have proved normal and then an AAI pacemaker has been implanted. Some weeks later, the patient reported a lipothymic episode; a Holter recording showed a second degree AV block, with normal pacemaker function. A DDD pacemaker has been implanted and in the next ten months the patient felt well. The sinus arrest physiopathology, the role of the autonomic nervous system and the correct electrostimulation mode have been discussed. PMID- 1881556 TI - [Post-infarction rupture of the interventricular septum. A report on 2 cases studied by color-coded Doppler]. AB - Rupture of interventricular septum is an infrequent but serious complication of acute myocardial infarction. We report the cases of two patients admitted to our department for acute myocardial infarction whose clinical course was complicated by rupture of the interventricular septum. They died from cardiogenic shock on the 13th and 6th days. Two dimensional and color coded echocardiography correctly detected the presence and the site of the rupture. PMID- 1881557 TI - [Left ventricular function in arterial hypertension in relation to age. The short term effects of nicardipine]. AB - The purpose of this study was to assess the age related effects on left ventricular function after acute administration of the calcium-antagonist nicardipine. Gated radionuclide left ventriculography was performed before and 90 min after 40 mg of oral nicardipine in a group of 15 male patients with essential hypertension (H), 8 younger (HY) and 7 older (HO) than 60 years, and in a control group of 15 male subjects without cardiovascular disease (C), 7 younger (CY) and 8 older (CO) than 60 years. Baseline ejection fraction (EF) was similar in groups H and C, while peak ejection (PER) and peak filling (PFR) rates were lower in hypertensive patients as compared to controls. Baseline EF and PER were similar in subgroups HY and HO as well as in subgroups CY and CO, while PFR was particularly lower in the older hypertensive patients HO. After nicardipine, EF PER PFR significantly increased in groups H and C; EF and PER significantly increased in subgroups HY HO CY CO, while PFR had a significant increase in subgroups HY CY CO, but showed a not significant increase in subgroup HO. After nicardipine, the percentage changes of ventricular volume indexes were similar in the 4 subgroups; end diastolic volume was unchanged, end systolic volume had a clear decrease, stroke volume and cardiac output increased. The hypertensive patients had a damaged diastolic ventricular performance, as compared to the normal subjects, while EF was near to normal range in groups H and C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881558 TI - [The clinico-instrumental evaluation of the efficacy of picotamide in treating chronic obstructive arteriopathies of the lower extremities]. AB - In 25 patients (19 males and 6 females) suffering from chronic arteriopathy of lower extremities at Fontaine stage II, the clinical efficacy of picotamide was investigated in double blind, cross over placebo-controlled study. Patients were assigned randomly to the treatment with placebo or picotamide (900 mg/die) for three months and, after 15 days of wash-out, to the treatment with picotamide or placebo for the same period. Painfree walking distance and ankle/arm systolic pressure ratio improved significantly only during picotamide treatment. Laboratory monitoring revealed a significant decrease in platelet aggregation and an increase of fibrinogen degradation products only during picotamide treatment. Three patients during picotamide treatment referred transient gastrointestinal discomfort (nausea, vomiting and diarrhoea); however in no case the treatment was suspended because of the appearance of these symptoms. These results indicate that picotamide is an effective drug in the management of chronic arteriopathy of lower extremities. PMID- 1881559 TI - [Maintenance therapy with beta-methyldigoxin in the elderly. A study of 40 patients]. AB - The efficacy of beta methyldigoxin was examined in a group of 40 elderly patients who had been hospitalised due to congested heart decompensation. A good clinical response was obtained in 95.5% of cases with the presence of slight toxic phenomena in 2 cases only (4.5%). The paper underlines the excellent pharmacokinetic pattern of the substance used in the steady state. Steady state digitalemic values were within the acceptable range in 83.76% of cases, whereas underdosage and overdosage phenomena were observed in 6.87% and 9.37% of patients respectively. PMID- 1881560 TI - [The acute treatment of supraventricular tachycardia with endovenous amiodarone]. AB - In the present study we evaluated 35 patients of both sexes, aged 21-84, with newly occurring supraventricular tachyarrhythmias, 19 atrial fibrillation (AF), 6 atrial flutter (FL) and 10 paroxysmal supraventricular tachycardias (PSVT). They were treated with a single amiodarone infusion up to two hours after the restoration of a stable sinus rhythm or to a maximus dose of 2,400 mg (in 24 hours). Plasma amiodarone concentration and QTc were measured at the restoration of sinus rhythm and twelve hours after the amiodarone withdrawal. Amiodarone infusion restored a stable sinus rhythm in all 10 patients of the PSVT group (100%), in 5 of the FL group (83%) and in 16 of the AF group (84%). The average dose needed to stop PSVT was lesser than for AF and FL (M + SE: 473.3 +/- 36.88 vs 1842.1 + 259.6 vs 1548.8 +/- 345.5 mg; p less than 0.001). The average plasma amiodarone concentration at the restoration of sinus rhythm was 2450.4 +/- 175.9 SE ng/ml in all the tachyarrhythmias as a whole without any statistically significant difference among PSVT, FL and AF. Moreover no correlation exists between plasma amiodarone concentrations and the amount of amiodarone infused. QTc showed a statistically significant transient lengthening at the restoration of sinus rhythm, but not twelve hours after amiodarone withdrawal. In conclusion, a single dose of amiodarone is effective and safe in all newly occurring supraventricular tachyarrhythmias, without any important side effect and with a high therapeutic index in pharmacologic cardioversion as alternative treatment to cardioversion. PMID- 1881561 TI - [Abdominal aortic aneurysm and horseshoe kidney. Clinical cases]. AB - The concomitance of horseshoe kidney and abdominal aortic aneurysm is rare but represents an interesting challenge for vascular surgeons. The trouble is greater if the diagnosis is formulated intraoperatively and specially if it is an emergency operation for aortic rupture or fissuration. The surgeon's aim is to get to the aneurysm collar without damaging the kidney, the renal arteries or the urinary tract that often have an anomalous development. The authors make a review of the literature and describe three cases occurred out of 2558 prosthetic reconstructions due to abdominal aortic aneurysm. PMID- 1881562 TI - [Cervical endoscopy for rational colposcopic evaluation]. AB - Having analysed the results of a large series of patients, the Authors propose endocervical examination as a vital step to be performed at the same time as colposcopy or, in certain well identified cases, following cytohistological results. Endocervical examination either before or after colposcopy is then described in a protocol taking into account the various parameters. The most important are: the assessment of the squamocolumnar line, the type of colposcopic lesion, and cytohistological findings. Following a brief discussion of traditional diagnostic tests (endocervical curettage, endocervical observation using Kagan forceps), the Authors underline the importance of the endocervicoscope which allows a closer, noninvasive and precise evaluation to be made. PMID- 1881563 TI - [Hysteroscopy as a method of evaluation of endometrial pathology during climacteric ]. AB - The Authors analyse 207 hysteroscopies performed in the outpatient clinic in women during menopause, without the use of dilatation or local anesthetic. The test was completed in 175 patients (84.6%). Tolerability was acceptable in 95% of cases. The main indication (80%) was atypical secretions during menopause or changes in the menstrual cycle. Hyperplastic lesions were confirmed in 12% of the tests carried out. An endometrial K was diagnosed in 5 cases (2.9%). The method showed a good level of specificity of diagnosis but it not always sufficiently sensitive. It is therefore necessary to complete the test by taking a selected histological sample using Novak's cannula. PMID- 1881564 TI - [Comparison of metroplasty by Strassman's method and by Tomkins' method. Retrospective study of 30 years]. AB - The study aimed to evaluate the usefulness of metroplasty to improve gestational ability in the presence of uterine malformations. From the analysis of results, it is clear that this surgical operation is undoubtedly efficacious when performed in selected patients (earlier negative obstetric outcome). The comparison of the two techniques (Strassman vs Tompkins) confirms that the latter produced better results in this series of patients. PMID- 1881565 TI - [Comparison of cytology and ELISA in the research on cervical Chlamydia infection]. AB - Papanicolaou smears from 100 woman with ELISA Chlamydia-positive (42) and negative (58) endocervical smears were examined. Chlamydial endocellular inclusions were found in 3 ELISA positive and 2 negative smears, with an evident low sensitivity (7%) of cytology in the diagnosis of the endocervical infection. Furthermore, by statistical analysis it is clear that a negative test doesn't add anything to the pre-test probability (prevalence) of the infection. On the other hand a positive pap-smear adds a poor information, if compared with immunoenzimathic assay and IF staining. Thus, the Papanicolaou smear can't be considered of diagnostic value for Chlamydial infection. Furthermore, it proves unsuitable even for screening programs on high-risk patients, concerning which the immunoenzymatic assay appears, as previously affirmed, the most suitable effort. PMID- 1881566 TI - [Magnesium in obstetric pathology]. AB - Mean levels of maternal blood magnesium in a group of pathological pregnancies were compared to levels found in a group of physiological pregnancies. The paper concludes that low levels of blood magnesium are an improbable condition in pregnancy due to the existence of protective mechanisms, and that they are therefore rarely the cause of the most common obstetric pathologies. PMID- 1881567 TI - [Hematocrit and hemoglobin, parameters of hematic viscosity, in pregnancy-induced hypertension]. AB - During pregnancy because of physiologic hemodiluition and changes in various plasma protein levels, plasma viscosity is decreased compared to the non pregnant condition. Specifically the whole blood viscosity profile throughout pregnancy follows that of the hematocrit. However some pathological condition like pregnancy induced hypertension and intrauterine growth retardation are characterized by an increase of plasma viscosity. In order to evaluate the effect of plasma viscosity on placental perfusion, in 41 patients affected by pregnancy induced hypertension and with no iron deficiency we compared maternal hemoglobin and hematocrit to the birth weight. High maternal hemoglobin and hematocrit levels were associated to an increased frequency of low weight for date newborns (less than or equal to 10th centile), although the relationship with the hemoglobin levels is stronger (p less than or equal to 0.02) than the one with the hematocrit (p less than or equal to 0.05). In contrast, high weight for date newborns (greater than or equal to 90th centile) were not related to maternal hemoglobin and hematocrit parameters. We found that maternal hemoglobin and hematocrit, indicators of plasma viscosity, are useful in predicting low birth weight, but not high birth weight. We speculate that hypoxia due to the modification of microcirculation is a very important factor in determining the low birth weight; in contrast the oxygen is not the only factor involved in determining the high birth weight. PMID- 1881568 TI - [Varicocele and male sterility]. PMID- 1881569 TI - [Tetridamine in the therapy of bacterial vaginosis]. AB - In this study 14 women suffering from symptomatic bacterial vaginosis were treated with tetridamine at a dose of 2 lavages/day for 7 days. The results obtained confirmed the value of tetridamine on account of the high percentage of recovery, the rapid diminution in the degree of bacterial infection and the excellent tolerability of the product. PMID- 1881570 TI - [Cervico-vaginal screening in the Abruzzo region]. AB - This study focuses on cervical cancer and the importance of establishing a suitable screening programme. The results of a study carried out in the Abruzzo region during a 10-year sample period are reported. A Population of 36,663 patients, of which 3,372 had never been screened, was included in the study. All patients were attending the Centre of Cytology and Colposcopy at the Clinic of Obstetrics and Gynecology in L'Aquila. In order to make progress in both the diagnosis and treatment of this pathology, it is necessary not only to obtain an interdisciplinary approach with constant cooperation between professional colleagues (cytologist, colposcopist and histologist), but also an increased sensitivity of the population to the need for screening. PMID- 1881571 TI - [Cases of endometrial hyperplasia diagnosed at a regional hospital in the Province of Pavia]. AB - Two hundred and fourteen cases of endometrial hyperplasia were diagnosed at the Hospital of Casorate (USSL 77, Pavia) between 1 january 1984 and 31 december 1989. Cases were subdivided as follows: 60 glandular hyperplasias, 54 glandular cystic hyperplasias, 83 adenomatous glandular hyperplasias, 13 atypical glandular hyperplasias and 24 cases of endometrial cancer. The analysis of data shows an increase in hyperplasia, but only the adenomatous and atypical varieties have a potentially carcinomatous evolution. PMID- 1881572 TI - [Endometrial carcinoma with simultaneous endometrioid carcinoma of the ovary. Report of two clinical cases]. AB - The paper reports two cases of simultaneous endometrial carcinoma and endometrioid carcinoma of the ovary. The clinical and pathological characteristics are examined. Both patients underwent radical surgery with an intraoperative examination for metastatic involvement of the lumbo-aortic, iliac and infundibulo-ovarian lymphonodes. Surgery was followed by antiblastic (cisplatin, adriamycin, cyclophosphamide), hormonal (progestogens) and immuno modulating (thymostimulin treatment). The two patients (respectively approximately 10 and 7 years after the operation) both enjoy good health. PMID- 1881573 TI - [Epidermoid cysts of the ovary. Presentation of a case of unusual dimensions]. AB - One case of large epidermoid cyst of the ovary is presented. This rare lesion was uniformly described previously in literature as incidental finding in the study of hysterectomy specimens. PMID- 1881574 TI - Systemic meningococcal disease: the diagnosis on admission to hospital. AB - The clinical and laboratory findings in 176 patients hospitalized with suspected systemic meningococcal disease (MCd) are presented. All except nine patients were prospectively included in the MenOPP study. One hundred and fifteen patients were most likely to have meningococcal disease, of these 71 were confirmed with growth of meningococci in blood and/or cerebrospinal fluid (CSF). The remaining sixty one patients served as the control group. Both petechiae, reduced general condition, and reduced consciousness proved valuable in the diagnosis of MCd. Petechiae was the clinical sign best discriminating between MCd and the control group. Ecchymoses were specific for meningococcal disease. Among the laboratory tests C-reactive protein (CRP) and Thrombotest (TT) were the tests which most frequently were found to be abnormal in patients with meningococcal disease. A diagnostic score is computed by the aid of a multiple regression analysis. This score includes the variables skin hemorrhages, body pain, CSF cell count, TT, CRP and white blood cell count. For a patient hospitalized with suspected MCd a score of three or more supports the diagnosis and should indicate the need for rapid antibiotic therapy. PMID- 1881575 TI - Comparison of two syphilis antibody assays based on cardiolipin antigen. AB - Two different antisyphilis screening tests based on cardiolipin antigen, the VDRL test and an RPR test (Sysmic, Diagast), were compared. A total of 2155 sera were examined by both tests. Positive results were confirmed with TPHA and TPI tests. RPR Sysmic test was as sensitive and specific as the VDRL. However, the RPR Sysmic test was easier and quicker, especially when the number of sera tested was high. PMID- 1881576 TI - Prognostic markers in diarrhoea-associated haemolytic-uraemic syndrome: initial neutrophil count, human neutrophil elastase and von Willebrand factor antigen. AB - The observed increase in plasma von Willebrand factor antigen (vWF:Ag) in patients with the haemolytic-uraemic syndrome is presumed to be secondary to endothelial damage, which is a central event in these diseases. As the prognostic value of such changes has not been previously evaluated, vWF:Ag has been measured in plasma from children reported to a national survey of haemolytic-uraemic syndrome. Human neutrophil elastase was also measured, as an initial neutrophilia has been shown to have prognostic value in diarrhoea-associated haemolytic uraemic syndrome. Despite a significant elevation of plasma vWF:Ag concentration in these patients at presentation, the values did not correlate with the period of thrombocytopenia, the need for dialysis, or outcome. However, children with a poor outcome had significantly greater plasma elastase concentrations compared to those who had a good outcome. PMID- 1881577 TI - Diurnal variation in urinary protein excretion in diabetic nephropathy. AB - We examined the diurnal variation in urinary excretion rate of albumin, IgG and beta 2-Microglobulin (beta 2-M) in healthy volunteers (n = 24), and in patients with type I diabetes mellitus having normal albumin excretion rate (less than 20 micrograms/min; n = 16), incipient diabetic nephropathy (albumin excretion rate 20-200 micrograms/min; n = 12) and clinical diabetic nephropathy (albumin excretion rate greater than 200 micrograms/min; n = 12). Diurnal variation was defined as [(overnight minus daytime): daytime excretion rate] times 100%. Median diurnal variation in albumin excretion rate in the various groups varied from -32 to -57%, and in IgG excretion rate from -42 to -65%, being not significantly different between the proteins or between the groups. Diurnal variation in beta 2 M excretion rate was similar in healthy volunteers and in patients with normal albumin excretion rate or incipient diabetic nephropathy (median -36 to -43%), but significantly reduced in patients with clinical diabetic nephropathy (median 0%; P less than 0.005), nine of whom had elevated beta 2-M excretion rates, suggesting tubular dysfunction. Except for beta 2-M excretion rate in patients with clinical diabetic nephropathy, the diurnal variations in albumin excretion rate, IgG excretion rate and beta 2-M excretion rate were larger than the diurnal variation in creatinine excretion rate (median -7 to -11%, P less than 0.005). Diurnal variations in albumin excretion rate and IgG excretion rate were highly correlated (r = 0.89, P less than 0.00001). These data suggest that similar mechanisms may account for diurnal variations in albumin excretion rate and IgG excretion rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881578 TI - A comparison of parathyroid-gland function in haemodialysis patients with different forms of renal osteodystrophy. AB - Parathyroid function was studied in three different histological forms of renal osteodystrophy: osteitis fibrosa (OF), low-turnover aluminium-associated bone disease (LTAABD), and aplastic bone disease without aluminium (ABD). Parathyroid function was determined by the evaluation of the sigmoidal parathyroid hormone (PTH)-calcium curve, which was obtained by the performance of a reduced calcium and an increased calcium haemodialysis. Parameters of the sigmoidal PTH-calcium curve evaluated included maximally stimulated (PTHMax) and inhibited (PTHMin) PTH, the set point of calcium for PTH (ICA50), defined as the ionised calcium concentration at which PTHMax was reduced by 50%, the ratio of basal PTH to maximally stimulated PTH (PTHBase:PTHMax), the ionised calcium concentration at which basal (ICABase), maximally stimulated (ICAMax), and maximally inhibited (ICAMin) PTH values were observed, and the slope of the PTH-calcium curve. Both PTHMax and PTHMin were greater in OF than the other two groups (P less than 0.02). The ratio of basal to maximally stimulated PTH was greater (P less than 0.02) in OF (61 +/- 7%) than LTAABD (33 +/- 5%) and ABD (36 +/- 7%). The ICA50 and the ICAMax were greater (P less than 0.03) in OF than the other two groups; however, no differences were observed in the ICABase and ICAMin. The slope of the PTH-calcium curve (% maximal PTH), which should indicate the sensitivity of parathyroid cells, was greater in OF than LTAABD (P less than 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881579 TI - Fluid balance during haemodialysis and haemofiltration: the effect of dialysate sodium and a variable ultrafiltration rate. AB - One of the main causes of hypotension during extracorporeal renal replacement therapy is an insufficient substitution of the ultrafiltrated plasma water by tissue water. To investigate the fluid balance and its effects on hypotension in dialysed patients, the following variables were studied: intracellular fluid volume (IFV) and extracellular fluid volume (EFV), blood volume (BV) and blood pressure. IFV and EFV were measured by means of non-invasive electrical conductivity measurements using four electrodes round the leg. Fifteen haemofiltration (HF) and 15 haemodialysis (HD) patients were studied. The latter group was dialysed in three ways: (1) conventionally, i.e. with dialysate sodium of 138 mmol/l (HD) (2) with a variable dialysate sodium (first half: 138 mmol/l; second half: 146 mmol/l) (HDS), and (3) with the same variable dialysate sodium and an ultrafiltration profile (two-thirds was withdrawn during the first half of treatment, the remainder during the second half) (HDSU). Hypotension frequency was less during HDS, HDSU, and HF compared to HD. This was caused by a more stable blood volume due to a better refill. During HD a fluid shift occurred from the EC to the IC compartment. The use of a high sodium dialysate concentration led to a transcellular fluid shift in the opposite direction. This fluid shift increased the refill, thereby stabilising blood volume. HF gave a better refill than HDS and HDSU, probably due to a reduced urea clearance. PMID- 1881581 TI - Five years experience with the Quinton Permcath for vascular access. AB - Over a five-year period 64 Quinton Permcaths were inserted into 51 dialysis patients (age range 17-72 years, mean 52.1 SD 12.83). The duration of catheter use ranged from 5 to 1479 days, mean 315.7 SD 337. The actuarial catheter survival rate at 1 year was 74%, at 2 years 43%, at 3 years 25% and at 4 years 12%. The indications for use were: exhausted peripheral access; CAPD contraindicated; abrupt failure or lack of an arteriovenous fistula; acute renal failure; limited life expectancy; patient insistence; conventional access contraindicated. Only minor complications occurred during insertion: haemorrhage requiring exploration in three patients and a temporary left recurrent laryngeal nerve palsy in one patient. The exit site infection and septicaemia rates were 4.95 and 3.36 per 1000 catheter days respectively. Eighteen catheters failed due to infection (range of use 72-1479 days, mean 559 SD 388). Inadequate initial blood flow (less than 150 ml/min) occurred in 10% of dialyses but only six catheters failed due to intractable flow difficulties (range of use 5-49 days, mean 22 SD 17.5). Catheter sepsis was implicated in the death of two patients. One subclavan/innominate vein thrombosis occurred. The Quinton Permcath represents a significant advance providing immediate, durable, and relatively safe access in a variety of difficult circumstances. PMID- 1881580 TI - Desferrioxamine infusion can modify EEG tracing in haemodialysed patients. AB - Neurological derangement has been reported in haemodialysed patients receiving intravenous desferrioxamine (DFO) for aluminium-related disorders. The possible direct effects of desferrioxamine on EEG recordings were investigated in ten haemodialysed patients who underwent a DFO test 2 h after the end of dialysis. According to a commonly accepted protocol, 40 mg/kg body-weight of desferrioxamine was infused in 60 min. EEG recording was continuously performed, starting 30 min before and stopping 30 min after the desferrioxamine infusion. Besides visual inspection, EEG records were digitised, tapered, and spectrally analysed with Digital PDP 11/73 microcomputer. Basal EEG recording was normal in all patients. In three patients a progressive EEG slowing was detected by visual inspection during desferrioxamine infusion; in these cases automatic analysis revealed a 50% increase in power of slower frequencies 30 min after starting the infusion, when no changes in plasma aluminium concentrations are detected; a complete recovery was observed 30 min after desferrioxamine withdrawal. In one patient bilateral paroxysms of slow waves appeared, so we stopped desferrioxamine infusion. Two of the three patients who developed EEG abnormalities also had an increased aluminium body burden (positive DFO test). Results indicated that desferrioxamine per se can modify EEG in haemodialysis patients and that its effect is not mediated by acute increases of plasma aluminium concentrations. The finding of a positive DFO test in two of three patients with EEG changes may suggest that an aluminium-induced blood-brain barrier derangement could have played a role. However, prompt recovery after ceasing desferrioxamine infusion strongly suggests a direct role of desferrioxamine in the induction of EEG changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881582 TI - Anti-rejection therapy in renal transplantation: Use of the monoclonal antibody OKT3. AB - The success of anti-rejection therapy was evaluated in 65 cadaveric renal allografts immunosuppressed with cyclosporin. All first rejection episodes were treated with 0.5 g methylprednisolone given daily for 3 days. Second rejection episodes were treated with either a further identical 3-day course of methylprednisolone or a 10-14-day course of the monoclonal antibody OKT3. The peak creatinine during second rejection episodes was higher in patients treated with OKT3 (481 +/- 54 mumol/l; mean +/-SEM) than in those treated with methylprednisolone (320 +/- 59 mumol/l) (P = 0.036), suggesting more severe rejection in the OKT3 group. Despite this the rejection reversal rate was higher in the OKT3-treated group (100%) when compared to the high-dose methylprednisolone group (64%) (P less than 0.05) and the creatinine at 6 months was less in the OKT3 group (162 +/- 17 mumol/l) than in the methylprednisolone group (230 +/- 22 mumol/l). These data suggest that OKT3 is a very effective treatment for second rejection episodes following renal transplantation and yields improved renal functions in comparison with high-dose steroids. PMID- 1881584 TI - Successful use of recombinant human erythropoietin in pregnancy. PMID- 1881583 TI - Renal transplantation with a current T negative but historical T and/or B positive cross-match. AB - We report our experience of 36 renal transplanted patients against a current T negative allo-cross-match, but historical T and/or B positive allo-cross-matches, whatever the result of the current B cross-match. Additionally, we have determined the immunoglobulin class of the antibody directed against B and T lymphocytes. The graft survival rate did not differ between the 36 patients forming the study group, and the 229 patients transplanted within the same period with negative T and B, on current and historical sera, cross-matches. Within this study group there was no changes in graft survival rate for the following three subgroups, which were retrospectively defined: historical positive (14 patients) versus negative (22 patients) T cross-match, current positive (15 patients) versus negative (21 patients) B cross-match, and IgM (16 patients) versus IgG (20 patients) against B lymphocytes. In terms of transplant outcome, our policy was thus safe. PMID- 1881585 TI - Primary dissociated cell culture of embryonic rat metencephalon: presence of GABA in serotonergic neurons. AB - This study was performed to determine whether neurons, where gamma-aminobutyric acid (GABA) and serotonin (5-HT) coexist, represent neuronal entities which can survive in vitro. In dissociated cultures from 18-day-old embryonic rat metencephalon, it was possible to develop glial and neuronal cells. Among the neurons, some of them, which contain glutamate decarboxylase or are capable of accumulating [3H]GABA are GABAergic; others, containing tryptophan hydroxylase or 5-HT are serotoninergic. By combining radioautography and immunocytochemistry, it was possible to observe neurons where 5-HT and GABA coexist. Cultures might be a suitable model to study the functioning (release or synthesis of both neurotransmitters) of neurons where two classical neurotransmitters coexist. PMID- 1881586 TI - Neutrophil as a mediator of ischemic edema formation in the brain. AB - We investigated the contribution of neutrophils to brain edema formation using a transient focal ischemia model in rats. Rats were given anti-neutrophil monoclonal antibody (RP3) intraperitoneally to deplete circulating neutrophils. In RP3-treated rats, ischemic brain edema formation 1 day after reperfusion was significantly decreased compared to that of saline-treated control rats. We speculate that chemical mediators released by infiltrating neutrophils alter vascular permeability and play an important role in post-ischemic brain edema formation. PMID- 1881587 TI - The binding of cholinesterase inhibitors tacrine (tetrahydroaminoacridine) and 7 methoxytacrine to muscarinic acetylcholine receptors in rat brain in the presence of eserine. AB - Cholinesterase inhibitor tacrine (1,2,3,4-tetrahydro-9-aminoacridine) is known to interfere with the binding of specific ligands to muscarinic receptors with unusually steep binding inhibition curves. We investigated whether the concentration dependence of the inhibition of binding is associated with the inhibitory effect of tacrine on the activity of cholinesterases, and compared the effect of tacrine with that of 7-methoxytacrine. Tacrine was found to inhibit the specific binding of [3H]quinuclidinyl benzilate (QNB) in rat brain cortex with IC50 values of 11 microM both in the absence and in the presence of 100 microM eserine, which had been added to ensure complete inhibition of cholinesterases at all concentrations of tacrine; in the cerebellum, the IC50 value was 10 microM in the absence and 14 microM in the presence of eserine; Hill slope factors (nH) were in the range of 1.55-1.79 and were not significantly affected by the presence of eserine. 7-Methoxytacrine inhibited the binding of [3H]QNB with an IC50 value of 2.3 microM in the cortex and of 2.6 microM in the cerebellum. The results indicate that the degree and the steep course of the inhibition of [3H]QNB binding to M1 and M2 muscarinic receptors by tacrine do not depend on its inhibitory effect on cholinesterases, and that 7-methoxytacrine is likely to interfere with the function of muscarinic receptors 4-5 times more strongly than tacrine. PMID- 1881588 TI - Immunolocalization of the alpha isoform of smooth muscle actin in mouse astroglia in cultures. AB - In mouse astroglia colony cultures, cells display dramatic changes in their 'social behavior' during differentiation. The non-motile glioblasts progress through highly motile pro-astroblast and astroblast stages before becoming non motile fibrous astrocytes. These changes in the behavior of astroglia are paralleled by changes in the organization of their microfilaments. Immunofluorescence staining of the astroglia colony cultures with rhodamine phalloidin, which binds to actin filaments (F-actin) formed by any of the 6 actin isoforms and with monoclonal antibody to alpha-smooth muscle (alpha-sm) actin (an actin isoform typical of smooth muscle cells), shows that the majority of the cells are positive for both alpha-sm actin and F-actin. Approximately 15% of the cells, however, were negative for alpha-sm actin but stained positively for F actin, indicating that the actin of these cells belongs to isoforms other than the alpha-sm isoform. PMID- 1881589 TI - Axonal regeneration from central respiratory neurons of the adult rat into peripheral nerve autografts: effects of graft location within the medulla. AB - In adult rats, autologous segments of the peroneal nerve were implanted into the medulla oblongata at the level of the obex either on the midline (midline grafts, n = 4), where respiratory axons decussate, or on the left side (lateral grafts, n = 5) in the area of the respiratory cell bodies. Several months after the graft implantation, spontaneous unitary activities (n = 225) were recorded within the grafts and were found to arise from both central respiratory (R, n = 72) and non respiratory (NR, n = 153) neurons which were giving off regenerated axons along the nerve grafts. The graft reinnervation by respiratory axons was found to be significantly more abundant within the medullary lateral grafts than within the midline grafts. This finding offers further support of the conclusion that the reinnervation of grafts by axons from central neurons is enhanced when the graft is placed proximally to the cell bodies. PMID- 1881590 TI - Triazolam fails to induce sleep in suprachiasmatic nucleus-lesioned rats. AB - Rats with suprachiasmatic nuclei (SCN) lesions did not show increased sleep after triazolam (TRZ) injections at any dose from 0.2 to 1.6 mg/kg, whereas 0.4 mg/kg TRZ given intact rats in the middle of their activity phase significantly increased sleep. Across SCN-lesioned and intact rats, the amount of sleep before and after TRZ 0.4 mg/kg was negatively correlated. SCN-lesioned rats did not have a circadian activity-dominant period and so did not accumulate a biological sleep debt. Their lack of response to TRZ may have resulted from the absence of a sleep debt compared to intact rats injected in the middle of their activity phase. These data support our hypothesis that the homeostatic process controlling sleep gates benzodiazepine hypnotic efficacy. PMID- 1881591 TI - Lesions of the medial septal nucleus produce a long-lasting inhibition of T lymphocyte proliferation. AB - The influence of the central cholinergic system on the immune system was studied in Wistar rats by lesioning the medial septal nucleus. This lesion inhibited T cell proliferation of splenocytes and thymocytes induced by the mitogens concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) up to 25 days and did not affect proliferation at 40 days after lesioning. In contrast, the response to the B cell mitogen lipopolysaccharide from E. coli (LPS) was not affected at any time. These findings suggest a regulatory role of the cholinergic medial septal nucleus on T lymphocyte proliferation. PMID- 1881592 TI - Catechol blocks the fast outward potassium current in melanotrophs of the rat pituitary. AB - The effect of catechol on the fast voltage-gated K+ current (IK(f)) of acutely dissociated rat melanotrophs was investigated in whole-cell recordings. Half maximal inhibition of IK(f) occurred at an external concentration of 1.7 mM and this effect was associated with a decrease of the rate of the current decay. Internal catechol had no measurable effect on IK(f). Catechol appeared to be equally effective as a blocker of the slow voltage-gated K+ current (IK(s)). Despite this lack of specificity the blocking action of catechol was voltage- and frequency-independent and was rapidly reversible. Catechol therefore represents a useful alternative to 4-aminopyridine as a blocker of IK(f). PMID- 1881594 TI - Alpha 1-antichymotrypsin has a trophic effect on hippocampal neurons in vitro. AB - alpha 1-Antichymotrypsin (ACT) has been reported to be present in senile plaques, and ACT level is elevated in the sera of patients with Alzheimer's disease. We found that ACT has a neurotrophic activity in vitro, i.e., it enhanced neuronal survival under the culture conditions used. Hippocampal neurons were cultured in chemically defined medium containing ACT at various concentrations. In order to evaluate the number of surviving neurons semiquantitatively, enzyme immunoassay for microtubule-associated protein2 (MAP2) was carried out using anti-MAP2 antibody. Cells cultured in medium containing 4 micrograms/ml of ACT showed 1.8 fold more neurotrophic activity than those cultured without ACT. PMID- 1881593 TI - Trans-ACPD (trans-D,L-1-amino-1,3-cyclopentanedicarboxylic acid) elicited oscillation of membrane potentials in rat dorsolateral septal nucleus neurons recorded intracellularly in vitro. AB - Glutamate receptors coupled to phosphoinositol turnover have been identified recently and named 'metabotropic' receptors. However, the exact functional roles of these receptors are still unknown. Trans-ACPD (trans-D,L-1-amino-1,3 cyclopentanedicarboxylic acid) is suggested to be the only selective agonist for metabotropic glutamate receptors. Here we report that trans-ACPD elicits membrane potential depolarization with oscillation of dorsolateral septal nucleus neurons recorded intracellulary in vitro. Our experiments also suggested that there may be multiple interactions between ionotropic quisqualate receptors and metabotropic glutamate receptors. The burst firing induced by high concentrations of trans-ACPD suggests that excessive activation of metabotropic glutamate receptors may lead to cellular toxicity or be associated with clinical disorders such as epilepsy. PMID- 1881595 TI - Responses of trigeminal subnucleus oralis nociceptive neurones to subcutaneous formalin in the rat. AB - Extracellular recordings of 33 single nociceptive neurones of the trigeminal subnucleus oralis (SNO) were made in rats under halothane nitrous oxide anaesthesia. These neurones were tested for their responses to a s.c. injection of formalin in their receptive field. Such a chemical noxious stimulation is known to induce a biphasic response of nociceptive dorsal horn neurones, the second period of which would be due to inflammation. Twenty-three neurones were characterized as nociceptive non-specific (NnS) and 10 as nociceptive specific neurones (NS). Formalin activated both SNO NS and NnS neurones, but, when they responded, NS neurones (n = 5) showed only the first phase of activity while NnS neurones showed either one (n = 13) or two phases (n = 6). Biphasic responses were most often observed for NnS neurones with A delta- and C-fibre inputs. These results indicate that the time-course similarity between the behavioural and the neuronal responses to formalin exists only for some SNO convergent neurones and that therefore the SNO does not seem to be very involved in the inflammatory component of the pain caused by formalin. PMID- 1881596 TI - Development of dendritic spines in the cerebral cortex of the micrencephalic rat following prenatal X-irradiation. AB - Postnatal development of dendritic spines (DS) on the 500-microns-proximal region of the apical dendrite of large layer V pyramidal neurons of the somatosensory cortex (Par 1) was studied with the rapid Golgi method in micrencephalic rats produced after exposure to 100 cGy X-irradiation at embryonic day 18. Treated rats examined at the age of 15 days had more DS than age-matched controls, whereas the reverse occurred in rats aged 30 days. After this time the number of DS decreased in normal rats. As a result, irradiated and control rats aged 90 days had about the same number of DS in the proximal region of the apical dendrite. These results suggest that development of DS appears early, and that natural overproduction and elimination of DS is impaired in the cerebral cortex of micrencephalic rats. PMID- 1881597 TI - The ejaculatory reflex in copulating rats: normal bulbospongiosus activity without apparent urethral stimulation. AB - Electromyographic activity was recorded from the bulbospongiosus muscles of intact, copulating male rats to test the hypothesis that urethral stimulation contributes to the ejaculatory reflex. Neither urethral anesthetization with lidocaine nor prevention of emission with guanethidine affected the rhythmic contraction of the bulbospongiosus muscle during the ejaculatory pattern. Urethral stimulation by the ejaculate apparently does not contribute to the regulation of the striated-muscle components of ejaculation-related reflexes in copulating male rats. PMID- 1881598 TI - Motor potentials evoked in tibialis anterior by single and paired cervical stimuli in man. AB - Latencies of compound muscle action potentials evoked in lower limb muscles after transcranial stimulation shorten and amplitudes enlarge when the target muscle is contracted. After transcutaneous stimulation of the cervical cord with single electrical stimuli, the latency is not affected by muscle contraction. This is thought to be due to a lack of temporal summation at the spinal motoneurones. Results are different when paired stimuli are used. With contraction most motoneurones respond to the first cervical stimulus while in a relaxed condition they respond to the second. Temporal summation brings motoneurones to their firing threshold. Therefore, cervical double stimulation is more effective than single stimuli. It is however less powerful than cortical stimulation. Paired stimuli are most powerful at an interval of 2 ms similar to the D I-wave interval after cortical stimulation. PMID- 1881599 TI - Quantitative increases in temporal lobe symptoms in human males are proportional to postnatal geomagnetic activity: verification by canonical correlation. AB - Enhanced geomagnetic activity during episodes of biochemical stress has been correlated with inferences of increased liability within deep temporal lobe structures. Because adult limbic epilepsy is frequently associated with perinatal hypoxia or metabolic disruption within this region, a weak positive correlation was expected between possible signs of mesiobasal temporal lobe lability in normal adults and perinatal geomagnetic activity. Canonical correlation demonstrated that young adult males (n = 243) displayed a positive (r = 0.31) relationship between the intensity of geomagnetic disturbance the day after birth only and a history of subjective depersonalization, anomalous visual and olfactory experiences. The effects was very clear when aa values exceeded 30 nT (gamma). Temporal lobe signs for these males were similar to those reported by normal young adult females (n = 313) who did not display any consistent correlation between these measures and perinatal geomagnetic disturbance. The results suggest that interactions between perinatal neurochemistry and the correlates of geomagnetic activity might permanently alter portions of the male limbic system. PMID- 1881600 TI - The normal emergence of the superior collicular map of auditory space in the guinea pig following developmental removal of visual cortex. AB - The normal development of the superior collicular map of auditory space in the guinea pig requires visual experience (Eur. J. Neurosci., 2 (1990) 682-692). The possible role of the visual cortex in this process was assessed by unilateral removal of the cortex prior to the crucial period during which visual experience is needed (Neurosci. Lett., 116 (190) 280-286). This removal did not affect the normal emergence of an ordered auditory space map in the superior colliculus. The cortico-tectal pathway does not appear, therefore, to play an essential role in the developmental dependence of the collicular auditory map upon visual experience. PMID- 1881601 TI - Feeding-induced increase in the extracellular concentration of histamine in rat hypothalamus as measured by in vivo microdialysis. AB - The extracellular concentration of histamine (HA) in the hypothalamus of conscious and freely moving rats was measured by in vivo microdialysis and the effects of fasting and feeding on the HA concentration were examined. In non fasted rats, the basal HA concentration was almost constant from 11.00 to 17.00 h on the day following implantation of the dialysis probe, the mean value being 11.1 pg/30 min. No significant change in the HA concentration was observed in rats deprived of food for 24 h. In 24-h fasted rats, feeding for 15 min produced a transient and significant increase in the HA concentration. These results suggest that histaminergic activity in the rat hypothalamus increases during feeding. PMID- 1881602 TI - Administration of testosterone alleviates the constitutive sex difference in rat brain cytochrome P-450. AB - Sex-related difference was observed in the levels of total cytochrome P-450 (P 450) and the mono-oxygenase activity mediated by P-450(b,e), namely, aminopyrine N-demethylase and morphine N-demethylase activity in rat brain microsomes. Male rat brain had higher activity of the above enzymes as compared to the female rat brain. On the other hand, P-450(c,d) mediated 7-ethoxycoumarin O-deethylase and benzo(a)pyrene hydroxylase activity showed no sex-related difference in rat brain. Administration of testosterone elevated the levels of total P-450, aminopyrine N-demethylase and morphine N-demethylase in female rat brain to levels comparable with that of the male rat brain. No significant change was observed in the levels of 7-ethoxycoumarin O-deethylase and benzo(a)pyrene hydroxylase and NADPH cytochrome c reductase. All of the above enzyme levels were unaffected in the male rat brain following the treatment with testosterone. These results indicate that testosterone may regulate the forms of cerebral P-450 that are associated with the sex-related difference observed in rat brain. PMID- 1881603 TI - Regional expression of transforming growth factor-alpha mRNA in the rat central nervous system. AB - The expression of transforming growth factor-alpha (TGF alpha) mRNA in various regions of the adult rat central nervous system (CNS), as well as in selected peripheral tissues was examined using Northern blot analysis. The highest expression was also found in the cerebral spinal cord, with the levels of TGF alpha mRNA being 5- to 6-fold higher in this tissue than in any other examined. Significant expression was also found in the olfactory bulb, anterior olfactory nucleus, corpus striatum, hippocampus, ventral mesencephalon and caudal brainstem. Of the peripheral tissues examined, only adrenal gland expressed TGF alpha mRNA at similar levels. Lower, but detectable, expression was found in prefrontal cortex, cerebral cortex and cerebellum. The latter levels were similar to those observed in lung, liver, kidney and, variable, salivary gland. These data demonstrate a widespread but differential distribution of TGF alpha mRNA throughout the rat CNS, and indicate relatively high levels of expression of this growth factor in central versus peripheral tissues. PMID- 1881604 TI - Immunocytochemical evidence for retrograde axonal transport of exogenous albumin in adult rat brain stem motor neurons. AB - Serum albumin is present in cranial nerve motor neurons in the brain. This is suggested to be due to uptake into peripheral axon terminals with subsequent retrograde axonal transport to the perikarya of the motor nuclei. Indirect evidence for uptake and retrograde axonal transport of albumin in a cranial nerve has been presented previously e.g. by demonstration of fluorescence of the albumin-bound dye Evans blue in the neurons of the hypoglossal nucleus subsequent to injection in the tongue. In this study we present direct evidence for retrograde axonal transport of albumin. Human albumin was injected into the tongue of adult rats, and immunocytochemically detected with an antibody, which selectively reacted with human albumin. In brains processed 24 hours or later after injection, a positive reaction was seen in the neurons of the hypoglossal nucleus. The immunoreaction product was localized as perinuclear granules in an otherwise unstained perikaryon probably associated with the endosomal-lysosomal system. Thus, albumin present in hypoglossal motor neurons appears to originate from uptake in peripheral axon terminals. Judging from the early appearance after injection, this transport probably occurs by a fast component of retrograde axonal transport. PMID- 1881605 TI - Specific transcellular carbocyanine-labelling of rat retinal microglia during injury-induced neuronal degeneration. AB - The present work employed a new technique for labelling phagocytizing microglia in the axotomized retinal of adult rats. Transection axotomy was performed within the intraorbital segment of the optic nerve, and the fast-transported, vital fluorescent carbocyanine dyes DiI and 4Di-10ASP were deposited at the ocular stump of the nerve in order to retrogradely prelabel the ganglion cells which were destined to die. Optic nerve transection resulted in progressive degradation of ganglion cell axons, perikarya and dendrites within the retina and in release of fluorescent material which was then incorporated into cells identified as microglia but not into other cells of the retina. Incorporation of labelled material into microglia occurred only when the ganglion cells degenerated and not when the non-lesioned ganglion cells were labelled from the superior colliculus. Double-staining of microglia with both dyes helped to compare the pattern of labelling for each dye. After progression of ganglion cell degeneration, microglia displayed a staggered, bilaminated distribution within the ganglion cell layer and within the inner plexiform layer. Fluorescent microglia were not found within the deeper layers of the retina indicating that transneuronal degeneration and subsequent labelling of microglial cells do not occur. The results show that one major function of microglia within the ganglion cell and inner plexiform layers of the lesioned retina is to remove debris produced after degradation of neurons. PMID- 1881606 TI - Discrimination of tetrahydroaminoacridine responders by a single dose pharmaco EEG in patients with Alzheimer's disease. AB - We report the results of our study suggesting that a single dose pharmaco-EEG may predict treatment response to tetrahydroaminoacridine (THA) in Alzheimer's disease (AD). 14 AD patients and 7 age-matched neurologically healthy controls were selected for the study. AD patients had 7 weeks' THA treatment. 6 patients were regarded as responders and 8 patients as nonresponders, respectively. AD patients as well as controls had a baseline EEG recording and next day another recording 90 minutes after a peroral single dose of 50 mg THA. The relative change from the baseline in the alpha-theta ratio was the most sensitive discriminator of responders and nonresponders (P = 0.004, ANOVA). PMID- 1881607 TI - Human fetal brain beta-nerve growth factor cDNA: molecular cloning of 5' and 3' untranslated regions. AB - The mRNA of beta-nerve growth factor (beta-NGF) has been demonstrated to be present in the human brain, both in adult and fetal stages of development. However, its complete nucleotide sequence is unknown since a full-length cDNA has yet to be isolated. We report here the cloning and complete analysis of the human fetal brain beta-NGF transcript. cDNA synthesis was performed from total brain RNA and overlapping regions of beta-NGF cDNA were enzymatically amplified and sequenced. The central portion of the cDNA was amplified using primers designed on the known genomic DNA sequence. The 5' and 3' unknown regions were amplified by the anchored polymerase chain reaction (PCR) and by complementary DNA Ends-PCR respectively. The latter method is an original variation of Inverted PCR. The sequenced transcript is very similar to the most common form of beta-NGF mRNA present in the mouse central nervous system. In addition, both the 5' and 3' untranslated regions show a high degree of homology to the corresponding murine sequences. PMID- 1881608 TI - Sensory nerve fiber terminals in the arachnoid granulations of non-human primates. AB - Myelinated and unmyelinated axons terminate within the arachnoid granulations. Serial section analysis by light and transmission electron microscopy reveals that the nerve fibers terminate at different locations or tissue compartments of the arachnoid granulation. 1. Myelinated axons ramify and terminate as free axon terminals like slowly adapting type II mechanoreceptors in the leptomeningeal connective tissue core of the granulation. 2. Myelinated and unmyelinated axons terminate in the transitional spongy zone which represents a tissue compartment for the diffusion of the cerebrospinal fluid from the subarachnoidal space to the venous sinus. This zone is composed of arachnoidal cells, dural neurothelial cells and fibrocytes. 3. Myelinated and unmyelinated axons terminate within lymphoid cell aggregation associated to the arachnoid granulation. PMID- 1881609 TI - Inhibition of nitric oxide synthesis induces a significant reduction in local cerebral blood flow in the rat. AB - The effect of intravenous administration of NG-monomethyl-L-arginine (L-NMMA, 30 mg/kg), a specific inhibitor of nitric oxide synthesis, on local cerebral blood flow (lCBF) was examined in the rat using the [14C]iodoantipyrine autoradiographic method. L-NMMA induced a statistically significant reduction in lCBF in the cerebral cortices as well as in various deep structures of the brain. This reduction in lCBF was accompanied by a clear increase in mean arterial blood pressure, suggesting that the cerebral resistance vessels constricted significantly beyond the autoregulatory response following L-NMMA administration. These findings indicate that the basal cerebral circulation may be closely related to nitric oxide production. PMID- 1881610 TI - Monosynaptic excitation of motoneurons innervating forelimb muscles following stimulation of the red nucleus in cats. AB - We examined the rubrospinal projection to forelimb motoneurons (Mns) in cats, in comparison with the corticospinal projection. Under pentobarbital anesthesia, intracellular recordings were made from forelimb Mns following stimulation of the red nucleus (RN) and the cerebral peduncle (CP). Single pulse stimulation of the RN produced excitatory postsynaptic potentials (EPSPs) in the majority of forelimb Mns (58/80, 72%). Segmental latencies of RN-EPSPs were shorter than 1.2 ms in 14 out of 22 Mns in which RN-EPSPs were detected in the C8-T1 segments, and in 3 of 36 Mns in the C6-C7 segments. The results suggest monosynaptic rubro motoneuronal connections in a substantial portion of forelimb Mns particularly in the C8-T1 segments. There was no evidence suggesting monosynaptic connections between cerebral cortex and forelimb Mns. PMID- 1881611 TI - Seeing speech: visual information from lip movements modifies activity in the human auditory cortex. AB - Neuromagnetic responses were recorded over the left hemisphere to find out in which cortical area the heard and seen speech are integrated. Auditory stimuli were Finnish/pa/syllables presented together with a videotaped face articulating either the concordant syllable/pa/(84% of stimuli, V = A) or the discordant syllable/ka/(16%, V not equal to A). In some subjects the probabilities were reversed. The subjects heard V not equal to A stimuli as/ta/ or ka. The magnetic responses to infrequent perceptions elicited a specific waveform which could be explained by activity in the supratemporal auditory cortex. The results show that visual information from articulatory movements has an entry into the auditory cortex. PMID- 1881612 TI - New plastic plates which enhance neurite extension in culture: roles of bisphenol A and tricyclodecanyl units for growth and orientation of neurites on plastic plates with microstructures. AB - In order to study molecular mechanisms of contact guidance of neurites, dissociated culture of adult mouse dorsal root ganglion (DRG) cells was performed for 6 species of plastic plates different in monomer compositions. Microstructures (grooves of 5-10 microns wide and 1 micron deep) were grafted on the plates so as to guide neurite growth in their axial direction. Neurites were longer and more oriented on plates with larger water contact angle. The distribution of neurites was uneven between grooves and steps of the microstructures, exhibiting a bell-shaped curve in relation to the water contact angle of the plastic. These indicate that hydrophilic properties of the plastic plate surface, due to the presence of bisphenol-A and tricyclodecanyl units, are crucially involved in the elongation and orientation of neurites. PMID- 1881613 TI - Reversed effect of caffeine on non-contractile and contractile Ca2+ mobilization operated by acetylcholine receptor in mouse diaphragm muscle. AB - Caffeine effects on contractile and acetylcholine receptor-related non contractile Ca2+ mobilization were investigated in phrenic nerve-diaphragm muscles of mice with neostigmine. Caffeine enhanced at 0.25-5 mM, and decreased at 7-20 mM the total amount of contractile Ca(2+)-aequorin luminescence (Ca2+ transients), but only decreased at 2-10 mM non-contractile Ca2+ transients. Pretreatment with formamide (2 M for 30 min) abolished contractile Ca2+ transients, but did not affect non-contractile ones. These results suggest that non-contractile Ca2+ mobilization is not due to direct Ca2+ release from sarcoplasmic reticulum, but due to direct modulation by nicotinic acetylcholine receptor. PMID- 1881614 TI - Protein kinase C in human pheochromocytoma. AB - Subtypes of protein kinase C were analyzed in adrenal and extra-adrenal pheochromocytoma of humans. Almost all protein kinase C of the adrenal tumor was type III, while the enzyme of the extra-adrenal tumor was separated into two major fractions corresponding to type II and type III by hydroxyapatite column chromatography. The extra-adrenal tumor but not the adrenal tumor spontaneously produced neurite-like processes when the cells were cultured in vitro. These results suggest that the high proportion of type II enzyme may reflect neuron directed differentiation in human pheochromocytoma. PMID- 1881615 TI - Investigations into the relationship between the dopaminergic system and ascorbic acid in rat striatum. AB - Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA) and dehydroascorbic acid (DHAA) were determined by HPLC in the striatum of male Wistar rats after single or repeated injections of apomorphine (1 mg/kg/day s.c.) and/or haloperidol (1 mg/kg/day i.p.), and 24 h after the last drug administration. Apomorphine significantly reduced the DOPAC/DA ratio and increased the DHAA/AA ratio; these ratio changes were significantly correlated (r = -0.9969, P less than 0.0005). Haloperidol greatly increased the DOPAC/DA ratio; the DHAA/AA ratio was also slightly increased, but there was no significant correlation. When apomorphine was associated with haloperidol, the resulting DOPAC/DA ratio was significantly lower than after haloperidol alone; the DHAA/AA ratio was also significantly reduced in contrast to the effect of apomorphine alone. It is concluded that a non-selective DA receptor activation mediates, in a correlated way, both the inhibition of DA turnover and the increase of AA oxidation in the rat striatum. PMID- 1881616 TI - Capsaicin desensitization to plasma extravasation evoked by antidromic C-fiber stimulation is not associated with antinociception in the rat. AB - The relationship of capsaicin desensitization to the antinociception produced by acute capsaicin administration was studied in the rat. Cutaneous application of 1% capsaicin (3 x/day) for 1 day antagonized plasma extravasation evoked by either 5% capsaicin applied to the dorsal surface of the hindpaw or antidromic stimulation of the saphenous nerve. Treatment with either 1% or 5% capsaicin (3 x/day) for up to 4 days failed, however, to produce thermal antinociception as measured by the rat paw-withdrawal procedure. In contrast, intracutaneous injection of 100 micrograms capsaicin produced marked increases in paw-withdrawal response latencies for up to six hours after injection. These data demonstrate a dissociation between block of cutaneous plasma extravasation and thermal antinociception in the rat. The data provide in vivo evidence that desensitization of peripheral nociceptors by capsaicin cannot account for the antinociception observed following acute capsaicin administration. Finally, these data support the notion that some pharmacologic actions of capsaicin in the rat can be dissociated from frank neurotoxicity on the basis of concentration or dose. PMID- 1881617 TI - Met-enkephalin immunoreactivity in the basal ganglia in symptomatic and asymptomatic MPTP-exposed monkeys: correlation with degree of parkinsonian symptoms. AB - The immunohistochemical localization of Met-enkephalin (Enk) was examined in the brains of normal monkeys (Macaca nemistrina), monkeys made parkinsonian by systemic MPTP administration and sacrificed while symptomatic, and monkeys exposed to low doses of MPTP over several months and sacrificed while asymptomatic for a gross parkinsonian motor disorder. The animals that had severe parkinsonian features had a large number of intensely Enk-immunoreactive perikarya in the putamen. Normal control animals had no Enk-immunoreactive perikarya while asymptomatic animals had small numbers of lightly to moderately stained perikarya in the putamen. Symptomatic animals also showed the most intense Enk immunoreactivity in the lateral globus pallidus (LGP) while the asymptomatic animals showed LGP Enk immunoreactivity intermediate between that seen in symptomatic and normal animals. These results suggest an increase in putamen Enk synthesis and LGP Enk content in animals with massive striatal dopamine depletions (greater than or equal to 97%) and which actively show parkinsonian features. Animals with slightly less striatal dopamine depletion and with no parkinsonian symptoms, had increased activity in this system but not to the extent seen in symptomatic animals. PMID- 1881618 TI - Spontaneous oscillations in cerebral blood flow velocity in normal humans and in patients with carotid artery disease. AB - Spontaneous oscillations in cerebral blood flow velocity (CBFV) in normals and in patients with stenoses or occlusions of the internal cerebral artery were measured using transcranial Doppler sonography. In normal subjects, large oscillations of up to +/- 30% from the mean CBFV were found with low frequencies between 0.4 and 9 cycles/min. No correlations between CBFV oscillations and systemic circulatory parameters were detected. In patients with carotid artery obstructions the CBFV oscillations were significantly reduced in the middle cerebral artery ipsilaterally to a hemodynamically significant lesion, but not contralaterally. Our results support the hypothesis that spontaneous oscillations (B-waves) of small pial vessels are responsible for the CBFV fluctuations. PMID- 1881619 TI - Bihemispheric organization of amygdalo-cortical projections in the rat. AB - Two fluorescent dyes were injected symmetrically into the prefrontal cortices of the left and right hemisphere. A consistent number of amygdaloid neurons was labeled from the injection in the contralateral cortex. Each nucleus of the basolateral amygdaloid complex showed a specific pattern of contralaterality. The highest degree of bihemisphericity was observed in the ventral basolateral nucleus. A significant number of neurons connected with the cortex of both hemispheres by means of axon collaterals was observed in the anterior basolateral nucleus. These anatomical findings indicate that the basolateral amygdaloid complex could act as subcortical link for interhemispheric communication. PMID- 1881620 TI - Reciprocal Ia inhibition in patients with spinal spasticity. AB - Reciprocal Ia inhibition from ankle flexors to extensors was studied in five patients with spasticity due to incomplete traumatic spinal cord lesions. Nine healthy subjects were tested as controls. Excitability of the soleus motoneuron pool was estimated by H-reflex testing in the resting state. Ia inhibition was activated by conditioning stimuli to the peroneal nerve. Ia inhibition was detected in all patients tested, the amount of inhibition ranging from 8% to more than 50% of the test H-reflex size. In the control subjects only weak Ia inhibitory effects were present. These findings indicate increased excitability of the Ia inhibitory pathway to ankle extensor motoneurons in patients with spasticity due to spinal cord injury. PMID- 1881621 TI - Do brief bursts of spike and wave activity cause a cerebral hyper- or hypoperfusion in man? AB - The correlation between brain activity and cerebral blood flow velocities during brief bursts of generalized spike and wave activity was analysed by simultaneous registration of the EEG and the intracranial flow patterns. The flow patterns of the middle cerebral artery were continuously recorded by means of transcranial Doppler ultrasonography using a specially developed monitoring system. A total of 25 bursts was investigated in 3 patients with spontaneous occurrence of generalized 3 Hz spike and wave activity and normal background EEG. Characteristic changes of the flow patterns were found in all cases: 3.41 +/- 0.98 s (n = 25) after the beginning of generalized spike and wave patterns, the flow velocity decreased by 25.84 +/- 10.45% (n = 25) below the 'preictal' flow velocity level. The period of flow velocity changes lasted several times longer than the phase of spike and wave activity. PMID- 1881622 TI - Failure of the oculomotor neural integrator from a discrete midline lesion between the abducens nuclei in the monkey. AB - Recent anatomical studies indicate that axons of neurons in the vestibular nuclei, projecting to the contralateral abducens nuclei, cross the midline at the abducens level. These axons then give off collaterals to the contralateral vestibular and prepositus nuclei that may be important for the neural integrator that converts eye-velocity to eye-position signals. We disrupted a subset of these commissural projections by making a small midline lesion between the abducens nuclei in a monkey. The vestibulo-ocular reflex and saccades were still present post-lesion, indicating that premotor drive was intact, but the lesion produced severe post-saccadic drift, indicating failure of the neural integrator. We conclude that commissural projections crossing at the abducens level may be important for oculomotor integration. PMID- 1881623 TI - Membrane electrical properties of external urethral and external anal sphincter somatic motoneurons in the decerebrate cat. AB - Membrane electrical properties of motoneurons innervating the striated muscle of the external urethral and anal sphincters were examined in the decerebrate cat. Both populations of motoneurons had similar electrical properties (mean pooled values; conduction velocity 48 m/s, membrane time constant 3.3 ms, afterhyperpolarization (AHP) duration 97 ms, membrane input resistance 2.2 M omega, rheobase 3.3 nA, and threshold voltage 8.1 mV). Although a portion of cells in both subpopulations of sphincter motoneurons displayed subthreshold conductances (i.e. sag, anomalous rectification), the incidence was higher in the external urethral sphincter motoneurons. The sphincter motoneuron membrane properties were likened to 'slow' hindlimb motoneurons and the low rheobase values suggest that the sphincter motoneurons are easily recruited. PMID- 1881624 TI - The eye in the brain: retinoic acid effects morphogenesis of the eye and pathway selection of axons but not the differentiation of the retina in Xenopus laevis. AB - We have analyzed the effects of all-trans retinoic acid (RA) on the morphogenesis, differentiation and projection of the eye of Xenopus. RA was applied in concentrations of 10(-5), 5 x 10(-6) and 10(-6) M at stages 9-17. Animals were reared until stages 40-48. RA applied before stage 11 1/2, abated completely formation of an eye or a retina, at later stages it led to the formation of microphthalmic eyes. Even in the absence of an eye parts of the forebrain had characteristics of the retina, but rods and cones reached then into the lumen of the third ventricle. The projection of eyes of RA-treated animals was revealed with rhodamine dextran amine. Ganglion cell axons projected bilaterally to the tectum, to the hindbrain, the contralateral retina and, occasionally, to the olfactory bulb. RA affects both morphogenesis of the eye and pathway selectivity of ganglion cell axons but not differentiation of the neural retina. PMID- 1881625 TI - Autoradiographic estimation of the extent of reversible inactivation produced by microinjection of lidocaine and muscimol in the rat. AB - We used autoradiography to examine the extent of reversible inactivation produced by microinjection of lidocaine (40 micrograms/microliters saline) and muscimol (1 microgram/microliter saline). We measured intracortical spread of tracer amounts of labelled drug and local changes in uptake of [1-14C]glucose produced by the microinjection. The maximal average radii of regions of drug spread were 1.7 mm for both [14C]lidocaine and [3H]muscimol and were achieved within the first 20 min postinjection. The width of lidocaine injections decreased at longer postinjection times (30-60 min) but the width of muscimol injections remained relatively constant (30-120 min). Lidocaine radioactivity decreased faster from the injection site than muscimol radioactivity. Glucose autoradiograms showed a discrete region of maximally reduced glucose uptake (1.4 mm for lidocaine and 1.0 mm for muscimol) surrounded by a region of less reduced glucose uptake (up to approximately 3 mm). These findings suggest that, in the cortex, the effects of focal inactivation extend beyond the region of drug spread. Diffuse effects may be mediated of disfacilitation of cortico-cortical circuits. PMID- 1881626 TI - Muscarinic receptor-mediated inhibition of voltage-activated Ca current in neuroblastoma x glioma hybrid (NG 108-15) cells--reduction of muscarinic agonist and antagonist potency by tetraethylammonium (TEA). AB - Patch clamp techniques were used to record voltage-activated Ca currents from NG 108-15 cells. The muscarinic agonists acetylcholine (ACh) and oxotremorine-M partially inhibited the Ca current (mean inhibitor 37%) with EC50 values of 0.32 microM and 0.14 microM, respectively. The EC50 for ACh in the presence of neostigmine (1 microM) was 0.11 microM. Tetraethylammonium (TEA) (10 mM) (10 mM) shifted ACh (+ neostigmine) and oxotremorine dose response curves to the right by 36- and 20-fold, respectively. TEA also inhibited muscarinic receptor binding (Ki values in brackets) of (i) N-methyl scopolamine ([3H]NMS) to homogenates of rat heart (86 microM) and rat submandibular gland (178 microM) and to intact NG 108 15 cells (358 microM) and (ii) [3H]pirenzepine binding to rat cerebral cortex homogenates (111 microM). Atropine antagonized muscarinic agonist responses and was found to have a pKB of 9.8 +/- 0.39, but 10 mM TEA reduced the potency of atropine by 69-fold, probably because of the weak antagonist action of TEA. PMID- 1881627 TI - Long-term potentiation of synaptic responses in the rat dentate gyrus is due to increased quantal content. AB - Long-term potentiation (LTP) of synaptic responses in the dentate gyrus neurons of the rat hippocampus was studied in in vitro slices with the use of intracellular recordings. The goal of the study was to determine if the expression of LTP is pre- or postsynaptic. LTP was induced by tetanic stimulation of the perforant pathway in the presence of bicuculline. The expression of potentiation was measured during low-intensity stimulation at 1-5 Hz. It was found that a 104% (S.E.M. +/- 35, n = 5) increase in the amplitude of evoked synaptic potentials was associated with a reduction in the number of transmission failures to 38% (S.E.M. +/- 15, n = 5) of the control values. The size of quantal responses was determined on the basis of asynchronous release from stimulated synapses. The average size of the quanta remained unchanged during LTP. The evident increase of quantal content suggests a presynaptic locus for expression of LTP. PMID- 1881628 TI - Hippocampal slices do not appear to accumulate low micromolar concentrations of quisqualate by an active uptake mechanism. AB - The ability of hippocampal slices to accumulate quisqualate by an active uptake process was investigated. All amino acid concentrations were measured by HPLC. Incubation of hippocampal slices for 4 min with 16 microM quisqualate at 25 degrees C led to measurable amounts of quisqualate within supernatant layers derived from slice homogenates. However, estimated tissue:original medium ratios of quisqualate were only 0.6. Addition of 100 microM ouabain did not alter the slice content of quisqualate but did promote marked elevations in the contents of aspartate and glutamate in the bathing medium. Quisqualate contents of the slices were approximately halved by ice-cold incubations or by inclusion of an excitatory amino acid receptor antagonist during the incubation. It is suggested that hippocampal slices do not actively accumulate this concentration of quisqualate and that at least part of the observed quisqualate in supernatant layers from slice homogenates is due to binding to extracellular amino acid receptors. PMID- 1881629 TI - Acute, but not repeated, cocaine administration decreases renin secretion in the conscious male rat. AB - The effects of cocaine on renin secretion have been addressed and a previously unreported inhibitory effect has been identified on this neuroendocrine system in the conscious male rat. Acute intraperitoneal administration of cocaine dose dependently (1.5, 7.5, 15, and 30 mg/kg; at 15 min) produced a significant decrease in both plasma renin activity (PRA) and plasma renin concentration (PRC). The time course of inhibition by cocaine in PRA and PRC revealed maximal effects at 15 min following a 15 mg/kg dose. In contrast, the long term administration of cocaine for 1, 7, or 30 days (15 mg/kg, twice daily, i.p.) did not produce changes in PRC. PMID- 1881630 TI - An anatomical study of the origin of sympathetic and sensory innervation of the elbow and knee joint in the monkey. AB - The origin of sympathetic and sensory innervation of the elbow and knee joint was studied by the intra-axonal transport method. After injection of WGA-HRP into the elbow and knee joint unilaterally in adult monkeys (macaca fascicularis), labelled cells were observed ipsilaterally in both the sympathetic and dorsal root ganglia. Following injection in the elbow joint the neurons were concentrated in the stellate and third to fourth thoracic (T3-T4) sympathetic ganglia, and in the fourth cervical to second thoracic spinal sensory ganglia. The knee joint injection resulted in labelling of sympathetic and spinal sensory ganglia, preferentially at the lumbo-sacral junction--the third lumbar to third sacral (L3-S3) ganglia. The functional implications are discussed in relation to pain mechanisms of joints and to an earlier hypothesis that the nervous system might be involved in the pathogenesis of chronic joint inflammation. PMID- 1881631 TI - Domoic acid induced seizure activity in rats. AB - Domoic acid, in increasing doses (10-300 pmol), was microinjected into the hippocampal CA3 region of rats. All rats consistently exhibited generalized bilateral electrical seizure discharge activity at 100 pmol of domoic acid. Seizure latency varied inversely with the dose of domoic acid in the range tested. Local hippocampal administration of gamma-aminobutyric acid (GABA) resulted in neuronal recovery from domoic acid-induced seizures. The seizure activity of domoic acid might be the result of decreased GABAergic inhibition. PMID- 1881632 TI - Vasopressin and angiotensin II are absent but spontaneously reappear in solitary hypothalamic neurons of the homozygous Brattleboro rat. AB - The homozygous Brattleboro rat (di/di) synthesizes a vasopressin (VP) precursor with a different C-terminus, which is not packaged in granules. In addition, the expression of a coexisting peptide, angiotensin II (Ang II), is disturbed. During postnatal life a small but increasing number of solitary post-mitotic hypothalamic neurons of the di/di rat undergoes a switch to a genuine heterozygous phenotype. Here we report the reappearance of Ang II in these heterozygous cells, which suggests that for the expression of Ang II a normal VP precursor is required. Based upon the present study and literature data it is proposed that at the level of the endoplasmic reticulum a compartmentalization of the synthesis of various peptide precursor occurs. PMID- 1881633 TI - Aspartate injections into the suprachiasmatic region of the Syrian hamster do not mimic the effects of light on the circadian activity rhythm. AB - The excitatory amino acids glutamate and aspartate are thought to be involved in the photic entrainment of the circadian pacemaker of the suprachiasmatic nuclei (SCN). When applied to the SCN region glutamate imitates the effects of dark pulses on the circadian activity rhythm rather than those of light. We have now injected aspartate into the SCN region of Syrian hamsters. These injections mimicked the effects of dark pulses as well, in so far as slight advances of the activity rhythm were obtained during the subjective day. However, the mean phase shift was not significantly different from the shift obtained with control injections. It is concluded that (1) aspartate has little or no effect on the phase of the circadian activity rhythm and (2) none of the putative transmitters of the photic afferents of the SCN produces the effects of light upon injection. PMID- 1881634 TI - Alzheimer's disease: size class frequency distribution of senile plaques: do they indicate when a brain tissue was affected? AB - The size class frequency distribution of a sample of senile plaques (SP) was determined in a total of 20 brain regions from 5 elderly cases of Alzheimer's disease (AD). The purpose of the study was to determine whether a comparison of the frequency distributions could be used to determine the chronology of SP development in the AD brain. SP from 10 microns to a maximum diameter of 160 microns were present in the tissue and the size class frequency distributions were positively skewed. The frequency distributions varied between brain regions in: (1) the size class containing the mode, (2) the degree of positive skew, and (3) the ratio of large to small SP. In most patients the ratio of large to small SP was higher in the hippocampus or adjacent gyrus compared with temporal, parietal and frontal neocortex. If the diameter of a SP reflects its age in the tissue than the data suggest that SP formed earlier either in the hippocampus or adjacent gyrus compared with the other neocortical tissues. However, this conclusion rests on a number of assumptions including: (1) that SP diameter is directly related to age, (2) that SP development occurs at similar rates in different brain regions and (3) that, once formed, SP are not removed from the tissue by astrocytes. PMID- 1881635 TI - Motile responses of isolated guinea pig vestibular hair cells. AB - Vestibular hair cells were isolated from the guinea pig vestibule by a micromechanical non-enzymatic procedure. Perfusion with 125 mM K+ solution induced irreversible slow shortening of the necks in 42.8% of the hair cells tested. Mechanical stimulation, creating a displacement of the hair bundle towards the kinocilium, induced either irreversible coiling or tilting of the neck of the cells, or reversible fast tilting of the cuticular plate (44.5% of tested cells). The response to the Ca2+ antagonist, Flunarizine, suggested that these movements were calcium-dependent. We propose several explanations of the physiological role of these mechanisms and discuss the possibility that fast tilting of the cuticular plate is a physiological movement involving the hair cells at the periphery of the vestibular receptors. The regulation of the vestibular message at the apex of type I hair cells is also considered. PMID- 1881636 TI - Influence of an acoustic preparatory signal on postural reflexes of the distal leg muscles in humans. AB - In standing subjects the sudden displacement of a platform toe-up evokes a stabilizing postural response of the anterior tibial muscle (long-latency reflex). A preparatory signal (acoustic warning stimulus) preceding the postural perturbation by 1 s results in a significant decrease in latency of this long latency response. There is no parallel modulation of the afferent cortical input in terms of evoked cerebral potentials following platform tilts toe-up nor of efferent cortico-spinal functions as evaluated by means of transcranial magnetic stimulation. Conceivable underlying mechanisms include faster intraspinal and/or intracortical processing of afferent input or switching to a shorter spinal reflex pathway. PMID- 1881637 TI - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity: partial protection against striato-nigral dopamine depletion in C57BL/6J mice by cigarette smoke exposure and by beta-naphthoflavone-pretreatment. AB - This study aimed to find a possible biochemical basis for the frequent epidemiological observation of a negative correlation between smoking and Parkinson's disease. The effects of cigarette smoke exposure and of beta naphthoflavone (BNF)-pretreatment on corpus striatal dopamine depletion by 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were studied using the mouse MPTP model. Brain and hepatic monoamine oxidase (MAO) activity, hepatic cytochrome P450 content, BNF-inducible ethoxyresorufin O-dealkylase (EROD) activity and corpus striatal dopamine levels were measured. Cigarette smoke exposure partially protected against corpus striatial dopamine depletion by MPTP. This protection was associated with monomaine oxidase (MAO) inhibition in brain and liver, as well as with cytochrome P450 induction. BNF pretreatment also partially protected against MPTP-induced depletion of striatal dopamine. This was associated with a strong induction of cytochrome P450 but not inhibition of MAO activity. Our findings suggest that both MAO inhibition and cytochrome P450 induction may play a role in any biochemical protection afforded by cigarette smoke exposure against the development of Parkinson's disease. PMID- 1881638 TI - Neonatal capsaicin treatment impairs functional properties of primary olfactory afferents in the rat. AB - Long-lasting influences of neonatal capsaicin treatment on functional properties of the olfactory nerve were studied in 30-day-old rats by determining excitability thresholds of nerve fibres by means of orthodromic field potentials elicited in the main olfactory bulb, as well as by analyzing the pattern of the low-frequency component of the bulbar electroencephalogram. In addition, body, brain and olfactory bulbar weights were measured. Neonatal capsaicin resulted in reduced excitability of primary olfactory afferents and reduced wave amplitude of the bulbar electroencephalogram. Capsaicin treated animals had reduced body, brain and bulbar weights, the latter being the most affected. The result indicates that capsaicin given early in life leads to altered transmission properties of olfactory nerve fibres at later age, suggesting that olfactory afferents are sensitive to the neurotoxic action of capsaicin as occurs in other chemosensory afferent systems. PMID- 1881639 TI - Benefits of bladder re-education. PMID- 1881640 TI - Incontinence. Pelvic floor re-education. PMID- 1881641 TI - Incontinence. Aids and appliances. PMID- 1881642 TI - Resource management demystified. PMID- 1881643 TI - TQM (total quality management): everyone's business. PMID- 1881644 TI - Holding the baby. PMID- 1881645 TI - Wound management. The diabetic foot. PMID- 1881646 TI - After 'pin down'. PMID- 1881647 TI - Betty Dean, squeaky clean. The ward visit. PMID- 1881648 TI - Shifting the cost. PMID- 1881649 TI - Incontinence in perspective. PMID- 1881650 TI - Ocular manifestations of congenital Marfan syndrome with contractures (CMC syndrome). AB - The authors present the results of ocular examination of six children with congenital Marfan syndrome with contractures (CMC syndrome). The ocular and neuroradiological findings of the CMC syndrome are discussed with reference to the literature. The ocular findings are: blue sclerae, megalocorneas, hypoplastic irides with complete translucency, miosis, spherophakia with or without lens dislocation and severe myopia. This study demonstrates that ophthalmological examination of children with congenital contractures and arachnodactyly is very helpful for diagnosis of the CMC syndrome. The authors stressed that ophthalmologists should not only look for luxation of the lens in children who are suspected of having CMC syndrome. Spherophakia was common in the children and could easily be observed through the translucent irides. Biometric evaluation of the eyes is recommended. All of the cases in this paper and reported cases are sporadic. No conclusions have been reached in the literature on whether the CMC syndrome represents the severe expression of the classical Marfan syndrome or a distinct entity. Maybe the answer will remain difficult, until the specific molecular defects in the collagen diseases are discovered. This study demonstrates that ophthalmological examination of the children with congenital contractures and arachnodactyly is very helpful for the diagnosis of CMC syndrome. PMID- 1881651 TI - Peters' anomaly: an unusual case. AB - The authors report on a case of congenital bilateral protruding corneal opacities. Clinical and histological examination was consistent with a diagnosis of Peters' anomaly with a defect in the endothelium and Descemet's membrane but without abnormalities of iris and lens. Corneal grafting was performed on both eyes. During a follow-up period of one year the corneas have remained clear. However, surgical intervention for glaucoma has been necessary. PMID- 1881652 TI - Axenfeld anomaly in association with hypomelanosis of Ito. AB - Hypomelanosis of Ito is a rare neurocutaneous disorder with associated ocular, facial, dental and skeletal abnormalities. The authors describe a case of hypomelanosis of Ito occurring with anterior segment mesenchymal dysgenesis of the Axenfeld type. An attempt is made to explain many of the major features of hypomelanosis of Ito in terms of neural crest origin, and to classify the disease as a neurocristopathy. PMID- 1881653 TI - Bilateral congenital ocular cysts. AB - This report presents an unusual case of bilateral congenital ocular cysts. These are in the spectrum of congenital cystic eye and microphthalmos with cysts. Diagnostic evaluation, including orbital B-scan ultrasonography, computed tomography and magnetic resonance imaging is described. Pathologic evaluation of the orbital cysts was consistent with congenital cystic eye. An associated microphthalmic eye was not detected with serial sectioning of both specimens. Examination of the orbit at exploration as well as pre- and post-operative MRI scans failed to demonstrate the presence of a microphthalmic eye in either orbit. Failure to detect a microphthalmic eye clinically, by diagnostic imaging studies, or serial microscopic sections of the cysts supports the diagnosis of congenital cystic eye. This child has associated mild facial clefting (median cleft lip and cleft palate) and basal cephalocele. Histopathologically documented cases of ocular abnormalities associated with basal encephalocele have not been reported. To the authors' knowledge, MRI findings of congenital ocular cysts have been reported once previously in a case of microphthalmos with cyst, however, histopathologic correlation has not been reported previously. PMID- 1881655 TI - Ophthalmology sourcebook and reference guide 1991-1992. PMID- 1881654 TI - Microphthalmos with colobomatous orbital cyst in trisomy 13. AB - The authors describe a case of trisomy 13 with microphthalmos and colobomatous cyst of the optic nerve and of the chorioretina with orbital extension, in a six month-old female patient. The colobomatous cyst has been studied by means of computerized axial tomography and ultrasonography in order to follow its evolution. The orbital cyst has not increased in size. PMID- 1881656 TI - Health status of salmonids in river systems in Natal. I. Collection of fish and parasitological examination. AB - A detailed microbiological and parasitological survey of salmonids and indigenous fish in the upper reaches of selected river systems in Natal was undertaken. Fish were collected from the rivers by electro-fishing, from dams by gill netting and from hatcheries along the rivers. A total of 678 fish from 26 different sites along 8 river systems were collected. No parasites could be detected on fish from four of the rivers tested. Parasites were, however, detected on fish from large production sites in Natal and in the rivers feeding these sites. Parasites which were detected were Ichthyopthirius multifiliis, various Trichodina spp., Apiosoma sp. and Gyrodactylus sp. The heads of all fish estimated to be less than one year of age were collected and examined for the spores of Myxosoma cerebralis. All of the samples were found to be free of this parasite. PMID- 1881657 TI - Health status of salmonids in river systems in Natal. II. Isolation and identification of viruses. AB - A total of 678 fish from 26 different sites along 8 river systems was examined for the presence of trout viruses. No isolations of any viruses were made from any fish collected from these systems in Natal during this study. No antibodies against any of the trout viruses were detected in the serum collected from these fish. It would appear from this study that the river systems in Natal are free of any of the known viruses of trout. Infectious pancreatic necrosis virus was, however, isolated from trout from the Natal Parks Board Hatchery at Kamberg Nature Reserve on the Mooi River during June and July of 1988. Neutralising antibodies against the VR 299 serotype of IPN virus were detected in the serum collected from trout at Kamberg in September 1988. PMID- 1881658 TI - Health status of salmonids in river systems in Natal. III. Isolation and identification of bacteria. AB - Both pathogenic and non-pathogenic bacteria were isolated from fish, both salmonid and non-salmonid, from selected river systems in Natal. Pasteurella pisicida was isolated for the first time from fish in South Africa. The isolation of Yersinia ruckeri, Aeromonas salmonicida, and Edwardsiella tarda were recorded for the first time from fish in Natal. A. hydrophila and Flexibacter columnaris were found to be widespread throughout the river systems in Natal. The Streptococcus species which caused serious disease problems in trout in the Cape Province and Transvaal was not isolated from any of the fish examined in Natal. PMID- 1881659 TI - The effect of tick infestation on the productivity of cows of three breeds of cattle. AB - The effect of tick infestation of Hereford, Bonsmara and Nguni cows on the weaning masses of their calves in a dipping versus non-dipping situation was investigated. Breed had a major effect on the level of tick infestation, Herefords being most susceptible and Ngunis least. The productivity of Nguni cows, as measured by the weaning masses of their calves was also least affected. The effect of infestation on the productivity of Hereford cows was the greatest and that on the Bonsmara cows was intermediate. It was estimated that each engorged female tick (predominantly Boophilus decoloratus) caused a reduction of 8.9 g, 8.0 g and 8.6 g in the weaning masses of calves from Hereford, Bonsmara and Nguni cows respectively. The effect of infestation on the productivity of the Nguni cows was nevertheless small because a limited number of ticks fed to maturity on this breed due to its natural resistance. PMID- 1881660 TI - A gas-chromatographic headspace method for the determination of acetone in bovine milk, blood and urine. AB - An automated headspace gas-chromatographic method has been developed for the determination of acetone in the milk, blood and urine of dairy cows. Five ml samples were saturated with 2 g of sodium chloride and equilibrated for 30 min at 90 degrees C in a Hewlett-Packard HP 19395 A automatic headspace sampler. The headspace volatiles were transferred without splitting to a 25 m x 0.3 mm x 0.4 microns Carbowax column in a Shimadzu GC 9A gas chromatograph, operating isothermally at 50 degrees C. The coefficients of variation for the determination of acetone were 1.5-4.4% for urine, 10.0-24.9% for milk and 2.0-19.6% for blood. The detection limits were 0.0055 mg/100 ml for milk, 0.0072 mg/100 ml for blood and 0.0080 mg/100 ml for urine. The analysis time of 5 min per sample provided an adequate rate of throughput for routine monitoring. PMID- 1881661 TI - A review of the ixodid ticks (Acari, Ixodidae) occurring in southern Africa. AB - Eighty-three species of ixodid ticks, as well as several entities that have yet to be described, occur in the Republic of South Africa plus the 4 independent states lying within its borders (Bophuthatswana, Venda, Transkei and Ciskei) and in Namibia, Botswana, Lesotho and Swaziland. They belong to the following genera: Amblyomma (8 spp.); Aponomma (3 spp.); Boophilus (2 spp.); Cosmiomma (1 sp.); Dermacentor (1 sp.); Haemaphysalis (10 spp.); Hyalomma (2 spp., one of them with 2 subspp.); Ixodes (25 spp.); Margaropus (1 sp.); Rhipicentor (2 spp.), and Rhipicephalus (28 spp). The history of tick research in this region is reviewed briefly and advances made by the major contributors to our knowledge are highlighted. Short comments on each genus are given. These are followed by information on every species known to occur in the region, presented under the following headings: Species diagnosis, under which references to relevant descriptions are listed and, where appropriate, notes on commonly used synonyms, related species and identification problems are included; hosts, indicating whenever possible the preferences of both the adults and the immature stages, as well as differentiating between common and incidental hosts, and distribution in terms of political (not ecological) divisions. PMID- 1881662 TI - [Opportunistic systemic mycoses]. AB - Systemic fungal infections can be primary or opportunistic. The mycoses caused by opportunistic pathogens become increasingly more important. These infections are mainly caused by Candida species, Aspergillus species, Cryptococcus neoformans, Mucor etc. The predisposing factors to these diseases are numerous: neutropenia, organ transplantation, use of steroids, broad spectrum antibiotics, antineoplastic chemotherapy, parenteral nutrition, prolonged intravenous infusions, extensive surgery etc. Mortality is high because many fungal infection are difficult to diagnose, especially in their early, more treatable stages. Considerable progress in treating these infections has been achieved. Systemic fungal infections, however, continue to present major problems, including clinical resistance, microbial resistance, emergence of new pathogens and involvement of more susceptible patients. The purpose of this paper is to review the recent progress and current problems in diagnosis, treatment and prevention of opportunistic systemic fungal infections. PMID- 1881663 TI - [Correlation between juvenile myocardial infarct in parents and plasma fibrinogen levels in their offspring]. AB - 140 children of parents who had acute myocardial infarction before age 45 and 75 healthy children without any familial history of coronary artery disease--as a control group--were investigated ranging in age from 3-18 years. It was found that plasma fibrinogen concentration significantly increased compared to age and sex adjusted control in sons of parents suffering from premature coronary artery disease. Results of this study suggest a significant association between parents' and children's fibrinogen level. It may be concluded from this study that the fibrinogen is a definitive marker for identifying risk children's. Preventive strategies in childhood should consider the role of this genetic factor in later manifestation of coronary artery disease and it would be necessary to emphasize the importance of eliminating environmental influences and change life-style in exposed families. PMID- 1881664 TI - [Fetal growth rate and its variations 1988/89]. AB - Considering that the last intrauterine growth standards were constructed more than two decades ago, the authors defined the measure of 5, 10, 25, 50, 75, 90 and 95 percentiles of birth weight on the base of Genetic and Obstetric Computer Register of East-Hungary, birth data having epidemiological value in Szabolcs Szatmar-Bereg, Hajdu-Bihar and Jasz-Nagykun-Szolnok counties in 1988-89. From the 36th week of pregnancy the mean values of birth weights between boys and girls, boys and gipsy boys, girls and gipsy girls as well as singular and twin newborn infants differed from each other significantly. Possessing these standards, the clinical judgement and supplying of the various newborn infants can be more exact. PMID- 1881665 TI - [Ultrasound-guided percutaneous external catheterization-drainage of pancreas related fluid collections]. AB - The authors have extended the diagnostics indispensable in drainage of pancreatic fluid collections by intracavitary invasive methods. In five patients exfoliative cytology, in to patients target biopsy and in other two septotomy were performed. Intracavitary invasive diagnostic and therapeutic methods may be useful complementary tools with the traditional technique. They can easily and effectively be carried out without complications if their utilization is well indicated. They may increase diagnostic accuracy and decrease discomfort of the patient in therapy. PMID- 1881667 TI - [Horus]. PMID- 1881666 TI - [Macrothrombopenia, nephritis and hearing loss--a new case of Epstein syndrome]. AB - A 14 years old boy with persistent proteinuria (1.6-4.0 g/day), microscopic haematuria, macrothrombocytopenia (giant platelets, platelet number 30 G/l), and a familial sensorineural hearing loss (the father and the brother were also affected) was studied. Kidney biopsy presented a diffuse mesangial proliferation, and a focal thickening of the glomerular basement membrane was seen on electron microscopy. With bone marrow aspiration normal number of megacaryocytes was observed. The aggregation response of the platelets was decreased on collagen, epinephrine and ADP but it was normal on aggristin. The presented case with nephritis, platelet disorders and hearing loss corresponds to Epstein syndrome, a variant of Alport's syndrome. PMID- 1881668 TI - [Ferdinand Hebra, pioneer of modern dermatology, born 175 years ago]. PMID- 1881669 TI - [Comparative activities of 15 beta-lactam antibiotics against 590 strains of Klebsiella pneumoniae according to the production of beta-lactamase]. AB - In October 1988, all non repetitive strains of K. pneumoniae isolated in 17 hospitals have been studied. Among these 590 strains: 451 (76%) only produce the specific beta-lactamase of the species SHV-1 (pI 7,7) or SHV-1 type (pI 7,1), while 74 (12.5%) produce a TEM-1 or TEM-2 type beta-lactamase, and 65 (11%) an extended broad spectrum beta-lactamase: 22 CTX-1, 5 SHV-2, 4 SHV-3, 26 SHV-4, 8 SHV-5. The minimum inhibitory concentrations of the following antibiotics were performed by a liquid micro dilution technic: amoxicillin (AMX), amoxicillin + clavulanic acid (CL), 5 mg/l, ticarcillin (TIC), piperacillin (PIP), cefazolin (CEZ), cefamandole (CFM), cefoperazone (CFP), cefotaxime (CTX), cefotaxime + clavulanic acid 5 mg/l, cefotaxime + sulbactam (SUL) 5 mg/l, cefpirome (CPI), ceftazidime (CAZ), azthreonam (AZT), latamoxef (MOX), cefoxitin (FOX), cefotetan (CTT), temocillin (TMO), imipenem (IMI). The "wild" strains with SHV-1 beta lactamase are resistant to AMX and have a decreased susceptibility to TIC and PIP, but are susceptible to other antibiotics. The TEM producing strains are more resistant to PIP and TIC, have a decreased susceptibility to CEZ and CFM but are susceptible to other antibiotics. For the extended broad-spectrum beta-lactamase producing strains, the MIC of penicillin antibiotics (AMX, TIC, PIP) are very high and also the MIC of CEZ, CFM and CFP. The MIC of CTX are higher for CTX-1 or SHV-4 producing strains, than for SHV-2, SHV-3, or SHV-5 producing strains. The combination with CL is more efficacious than the one with SUL to reduce the MIC of CTX in susceptibility area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881671 TI - [Uptake of ofloxacin by Escherichia coli]. AB - The uptake of ofloxacin by Escherichia coli NIHJ-JC2 was determined by a sensitive and convenient method using high-performance liquid chromatography (HPLC) with a fluorometric detection (sensitivity level: 1 ng/ml). Concentrations of ofloxacin were measured in bacteria after contact with 5 micrograms/ml of antibiotic for 1, 2, 3, 5, 10, 20 and 30 min. Ofloxacin uptake was rapid, 70% of broth concentration occurring within the first min and 96% after 5 min; then it reached a plateau which was 1.16 times as high as the broth concentration. PMID- 1881670 TI - [In vitro antibacterial activity of a new fluoroquinolone, temafloxacin, against hospital isolates. Results of a multicenter study]. AB - Minimal inhibitory concentrations (MICs) of temafloxacin (TMF) was determined by agar dilution for 2,510 bacterial strains isolated in 1989 in 9 university hospitals. Activity of TMF against nalidixic acid (NAL) susceptible (S) Enterobacteriaceae was close to that of other fluoroquinolones (FQ) (mode MIC: 0.06 micrograms/l); like for other FQ, this activity was reduced against NAL intermediate (mode 1) and resistant (R) (mode 4) Enterobacteriaceae. MICs of TMF against P. aeruginosa were between 0.12 and 128 (mode 0.5-1). TMF had also a good activity against NAL S A. baumannii (mode MIC: 0.06-0.12) but this activity is reduced against NAL R Acinetobacter (mode MIC: 16). TMF was highly active against Haemophilus mode MIC: less than or equal to 0.008), Gonococci (mode MIC: 0.008 0.032), Meningococci (mode MIC: 0.08) and B. catarrhalis (mode MIC: 0.016). TMF showed better activity to other fluoroquinolones against methicillin susceptible Staphylococci (mode MIC: 0.06); the resistant strains (mode MIC: 8) are usually methicillin resistant. Comparatively to the currently available FQ, TMF is so more effective against Enterococci (mode MIC: 1), Streptococci (mode MIC: 0.5-1) and Pneumococci (mode MIC: 0.5). Finally, for the anaerobic bacteria, TMF is more active against C. perfringens (mode MIC: 0.5) than against B. fragilis (mode MIC: 2). PMID- 1881672 TI - [Effect of fibronectin on the adhesion of staphylococci and interaction with pefloxacin's anti-adherence properties]. AB - Fibronectin (Fn) is recognized for its ability to mediate Staphylococcus aureus (SA) adhesion. The number of Fn receptors is dependent on the phase of growth, and type of media. Furthermore, it was of interest to examine SA and Staphylococcus epidermidis (SE) adherence to porcine Fn (IBF 10 ng/ml) immobilized on tissue culture plates. The aim of our study was to examine if removal of FN receptors by growing bacteria in an antibiotic containing medium decreased the ability to adhere and of pefloxacin (P) anti-adhesive properties were medium dependent. As SE usually lack Fn binding capabilities, it seemed of interest to investigate if the effects of subinhibitory concentrations of P were modified by medium or Fn. We found: a) For SA: whether Fn coated onto plastic substrata promoted adherence of strains, P's anti-adhesive properties were saved, non medium or phase of growth dependent. b) For SE: adherence properties were decreased if Fn was coated onto plates. P's anti-adhesive properties were not modified and non medium dependent. The number of Fn receptors on clinical isolates of SA correlates with the invasiveness of the isolates. As P reduced the binding of SA to Fn coated plates, this observation may have important implications for antimicrobial prophylaxis. PMID- 1881673 TI - [Comparative study of minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) values for tetracycline, monocycline, erythromycin and rokitamycin against eleven strains of Chlamydia trachomatis]. AB - We evaluated the efficacy of tetracycline, minocycline, erythromycin and rokitamycin (rikamycine, TMS-19Q) in controlling in vitro propagation of Chlamydia trachomatis in HeLa 229 cells. Ten recent clinical isolates of Chlamydia trachomatis and one fast-growing strain were tested with inocula of 100 1,000 inclusion forming units per well of a 96-wheel microculture plate. Chlamydia trachomatis inclusions were detected by an immunoperoxidase antiperoxidase procedure (PAP), including a genus-specific monoclonal antibody. Minimal inhibitory concentration (MIC) geometric means and ranges were respectively 0.128, 0.015-0.25 mg/l tetracycline, 0.001, less than or equal to 0.001-0.004 mg/l minocycline, 0.187, 0.031-0.5 mg/l erythromycin, and 0.005, less than or equal to 0.001-0.062 mg/l rokitamycin; minimal lethal concentration (MLC) geometric means and ranges were 6.79, 0.125-32 mg/l tetracycline, 0.225, 0.062-2 mg/l minocycline, 3.37, 1-32 mg/l erythromycin, and 0.112, 0.031-1 mg/l rokitamycin. Since rokitamycin appears to be the more bactericidal from the four antibiotics tested, clinical studies in sexually transmitted diseases are indicated. PMID- 1881674 TI - [Importance of the antimicrobial mode of action of antibiotics for their combined effect with glycine in subinhibitory concentrations on microbial growth]. AB - Following previous observations of an increase in microbial sensitivity to the bactericidal beta-lactams ampicillin and imipenem in the presence of glycine, the aim of the presented study was to examine if such an effect is due to the antimicrobial mode of action of an antibiotic and/or to its bactericidal or bacteriostatic capacity. Using growth curves as an experimental parameter the same synergistic glycine effect could be shown if tested concomitantly with a number of other antibiotics acting equally on bacterial cell wall formation as cefaclor, cefadroxil, or fosfomycin. This glycine effect is, therefore, associated with the antibiotic mode of action, but is independent of wether the antibiotics are beta-lactams or not (fosfomycin). In contrast, glycine had no particular effect in combination with antibiotics inhibiting protein synthesis (sisomicin, kanamycin, chloramphenicol, oxy-tetracycline) or nucleic acid polymerase activity (ciprofloxacin, cinoxacin; rifampicin being a certain exception) as well as with those acting on cytoplasmic and external membrane as polymyxin B. The synergistic effect of glycine and cell wall active antibiotics was interpreted predominantly by an action on carboxypeptidases. PMID- 1881675 TI - Rapid antimicrobial susceptibility testing of gram-negative bacilli using Baxter MicroScan rapid fluorogenic panels and autoSCAN-W/A. AB - The MicroScan Rapid Neg MIC/Combo panels and autoSCAN-W/A (Walk Away) system utilize automated fluorescence technology for rapid antimicrobial susceptibility testing of Gram-negative bacilli. In a three site clinical study eleven antimicrobial agents were evaluated by comparing results obtained with 741 clinical isolates, using rapid fluorogenic expanded dilution MIC panels and corresponding frozen microdilution reference panels determined visually. Results for 31%, 40%, 12% and 9% of the isolates were available within 3.5, 4.5, 5.5 and 7.0 hours respectively. Results for 7.3% were not available within that time period. For the seven drugs analyzed using a Minimum Inhibitory Concentration range of dilutions, overall agreement (+/- 1 dilution) was 94%, with 1.5% very major, 0.9% major and 2.5% minor errors. For the four drugs analyzed using a Breakpoint range of dilutions, overall agreement (+/- 1 dilution) was 97%, with two percent very major, and one percent major errors. The MicroScan Rapid Neg MIC system is an accurate and rapid method for same day determination of susceptibility of Gram-negative bacilli. PMID- 1881676 TI - Rapid antimicrobial susceptibility testing of gram-positive cocci using Baxter MicroScan rapid fluorogenic panels and autoSCAN-W/A. AB - The Microscan Rapid Pos MIC/Combo panels and autoSCAN-W/A (Walk Away) system utilize automated fluorescence technology for rapid antimicrobial susceptibility testing of staphylococci, streptococci, and Listeria. In a three site clinical study, panels containing 26 antimicrobial agents were evaluated by comparing results obtained with 605 clinically significant isolates, using rapid fluorogenic expanded dilution MIC panels and corresponding frozen microdilution reference panels. Results for 16%, 40%, 13%, 9%, 8%, 11% and 1% of the isolates were available within 3.5, 4.5, 5.5, 7.0, 8, 11 and 15 h respectively. Results for 2% were not available within that time period. Overall agreement (+/- 1 dilution) for the 14,609 efficacy comparisons was 96%, with 1% each for very major, major and minor errors. Interlaboratory reproducibility testing of 25 isolates in triplicate in each site, showed an overall essential agreement of 97%. The MicroScan Rapid Pos MIC System is an accurate, reproducible and rapid method for same-day determination of susceptibility of Gram-positive cocci. PMID- 1881677 TI - [Evaluation of an automated system in bacteriology. Application to bacteriological susceptibility tests]. AB - Susceptibility tests have been compared between a new automated system and the reference method by agar diffusion. The COBAS-Micro apparatus for bacterial susceptibility tests is intended for rapid determinations with, normally, an incubation time of 5 h at 37 degrees C. Its is compatible with strains requiring greater than 18 h incubation. With this technique a large range of antibacterial substances (greater than 60) can be studied, in groups of fifteen. With the help of a computerized soft-ware, one growth-index:EPR (End Point Ratio) is calculated, in comparison with a standard, for each antibacterial agent tested and expressed in three categories: SIR. The findings are optimized according to the limits prescribed by the NCCLS. The reference method, by agar-diffusion, is as described by the Comite de l'Antibiogramme de la Societe Francaise de Microbiologie (CA-SFM). A total of 1,048 strains were tested by the two techniques: 518 Gram negative rods, 530 Gram positive cocci, with four common antibiotics. The percentages of agreement between the two groups were: 96% full agreement and minor discrepancy, 4% major and very major discrepancy. This automated system seems to be perfectly suitable for susceptibility testing in a routine laboratory, especially with strains isolated from ambulatory patients. PMID- 1881678 TI - [Detection of extended broad-spectrum beta-lactamases with the ATB MIC system]. AB - The Enterobacteriaceae producing extended broad-spectrum beta-lactamases (ESB) must be detected even when their MIC to oxyiminocephalosporins are low. We tested 164 isolates (133 ESB, 31 non ESB) on two experimental ATB MIC plates containing cefotaxime or ceftazidime (0.06-128 mg/l) alone or associated with sulbactam (4 mg/l). Fifty four per cent of the ESB isolates are sensitive to cefotaxime, and 30% to ceftazidime. Respectively 95% and 94% of these bacteria have a synergism index (MIC CIII alone/MIC CIIII + sulbactam) greater than or equal to 4 with cefotaxime and ceftazidime. The isolates that do not produce ESB have all a rate less than 4. The ATB system can detect the extended broad spectrum beta lactamases when low concentrations of cephalosporins are used, alone and in association with an inhibitor of beta-lactamases. PMID- 1881679 TI - [Enterobacteriaceae isolated in nine general hospitals of the Ile-de-France in 1988 and 1989: susceptibility to beta-lactam antibiotics according to the length of hospitalisation]. AB - Susceptibility to beta-lactam antibiotics of strains of Enterobacteriaceae consecutively isolated in nine general hospitals during a period of 2 months (march and april) has been studied by the disk-agar diffusion method. The separation between susceptible and resistant strains was based on the measure of the inhibition zones centered by 2 disks: cephalothin and ticarcillin. Enterobacteriaceae were divided in 2 groups: strains isolated during the first 48 h of hospitalisation or isolated after. Fifty one per cent of the strains were isolated during the first 48 h: they did not belong to the residential flora of these hospitals. Klebsiella, Proteus indole positive, Providencia, Enterobacter, Serratia were more frequently isolated after 48 h of hospitalisation. Susceptible strains of Klebsiella, Proteus indole positive, Providencia, Serratia were more rarely isolated after 48 h of hospitalisation. E. coli whatever the duration of hospitalisation, is the less frequent susceptible bacterium. PMID- 1881680 TI - [Epidemiology of aminoglycoside resistance in Streptococcus except in group D Streptococcus and Enterococcus]. AB - During a ten month period (march-december 1989), all streptococcal strains isolated from clinical specimens sent to our laboratory were routinely tested for high-level resistance to aminoglycosides. High-level resistance was detected in 16 out of 475 streptococci: streptomycin (two strains), kanamycin (four strains), streptomycin and kanamycin (ten strains). PMID- 1881681 TI - [Frequency and antibiotic susceptibility of bacteria responsible for urinary infections in private practice from 1986 to 1990. Results of 5398 samples]. AB - For each year from 1986 to 1990, fourteen private laboratories from all over France collected epidemiological data on germs discovered in urinary infections in France. This retrospective and comparative study covers 5,398 dossiers. The sensitivity of germs in private practice in urinary infections (ampicillin, AM AC, cephalosporin, ceftriaxone, gentamicin, pipemidic acid, pefloxacin, cotrimoxazol) were analysed. Germ resistance tests carried out by the CMI study in the centre of reference (Pr Thabaut, HIA Begin) showed variable divergences according to the different antibiogram techniques employed by the private laboratories. PMID- 1881682 TI - [Binding of cefuroxime to macromolecules from bronchitic sputum in patients with chronic bronchitis]. AB - Cefuroxime binding to soluble bronchial macromolecules has been performed in vitro with preparations obtained from ten patients. Cefuroxime at various concentrations have been added to soluble macromolecules (10 g/l). Free cefuroxime has been obtained by equilibrium dialysis and measured by HPLC. Results show that cefuroxime binding is about 30% of total antibiotic. PMID- 1881683 TI - [Diffusion of imipenem in synovial fluid]. AB - The diffusion of imipenem (IMP) in the knee joint was studied after a 1 g i.v. administration of Tienam over one hour. The synovial fluid was collected under anesthesia during arthroscopy carried out for mechanical lesions of the knee (meniscal lesions after ligamental injuries or sequelae after meniscectomy), in 3 groups of six patients at one, two, or three hours after the end of injection of IMP. The concentrations of IMP determined by high performance liquid chromatography (HPLC) were: 42.5, 20.1, 9.3 and 5.7 mg/l in the blood at T0, T1, T2 and T3 hr, respectively; 20.4, 13.0 and 7.9 mg/l in the synovial fluid at T1, T2 and T3, respectively. The decrease of IMP concentrations in the synovial fluid was 1,5 times as low as in serum. On account of its broad-spectrum antibacterial activity and our data, IMP could be used in perioperative prophylaxis of the knee joint surgery. PMID- 1881684 TI - [Pharmacokinetics and tissue penetration of single-dose netilmicin used for antibiotic prophylaxis during colo-rectal surgery]. AB - Pharmacokinetics and tissue penetration of netilmicin were studied after the use of a single dose (6 mg/kg) given for antibioprophylaxis in colo-rectal surgery. Thirteen patients, scheduled for elective surgery, were given 6 mg/kg IV netilmicin over 30 min, together with 1000 mg IV ornidazole. Netilmicin peak serum concentration (10 min after end of infusion) was 24.4 +/- 3.4 mg/l and trough level (24 h) was 0.9 +/- 0.5 mg/l. Plasma elimination half-life was 409 +/ 70 min, le volume apparent volume of distribution was 38 +/- 101 and total body clearance was 0.07 +/- 0.02 ml/min. Adequate netilmicin levels (5 greater than or equal to CMI 90 of involved pathogens Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus) were obtained in 100 per cent of patients in abdominal wall and epiploid fat, at time of opening, and in colonic wall at time of anastomosis. Adequate levels were obtained at time of closure in abdominal wall and epiploid fat in 92 to 100 per cent of patients. In situation of allergy to beta-lactam antibiotics, the use of netilmicin in combination with ornidazole may be recommended. PMID- 1881685 TI - [Diffusion of roxithromycin in gingival tissue]. AB - The gingival penetration of roxithromycin was evaluated at steady-state in twenty nine patients treated by 150 mg orally every 12 h during five days. Tissue specimen were sampled at 2 h (n = 6), 4 h (n = 6), 6 h (n = 5), 8 h (n = 6) and 12 h (n = 6) after the 10th administration. One blood sample was drawn at the same times. Serum and tissue concentrations of roxithromycin were measured by high performance liquid chromatography (HPLC). Serum peak level, measured at the 4th h, reached 6.60 +/- 1.15 micrograms/ml. The tissue peak concentration was 4.63 +/- 1.84 micrograms/g at the 8th h. Between the 4th and 10th hour after administration, the tissue concentrations are above 2 micrograms/g, i.e. above roxithromycin MIC 90 against most of the encountered pathogens in stomatologic infections. PMID- 1881686 TI - [Diffusion of ciprofloxacin into bronchial secretions in mechanically ventilated patients]. AB - The aim of the study was to evaluate, in clinical conditions, the penetration of ciprofloxacin into bronchial secretions. Eight patients were included in the study. They presented with nosocomial pneumonia and were under controlled mechanical ventilation. Ciprofloxacin was given at a dose of 3 mg/kg over 30 min. Serial bronchial and blood samples were obtained over a 12 hour period on day 2 and 4. Ciprofloxacin was measured by HPLC. Serum peak levels were 2.95 +/- 1 mg/l on day 2, and 2.43 +/- 0.7 mg/l on day 4. Bronchial peak and through levels were 0.95 +/- 0.51 mg/l and 0.21 +/- 0.12 mg/l, respectively, on day 2, and 0.76 +/- 0.17 mg/l and 0.18 +/- 0.14 mg/l, respectively, on day 4. The ratio of bronchial/serum peak was 0.32 +/- 0.11 and 0.33 +/- 0.06 on day 2 and 4, respectively. The ratio of AUC 0-12 h in the bronchial secretions/AUC 0-12 h in the serum samples was 0.66 +/- 0.04 and 0.55 +/- 0.27 on day 2 and 4, respectively. PMID- 1881687 TI - [Diffusion of norfloxacin in epididymal tissue]. AB - Norfloxacin, a "second generation" compound of the quinolone group, was administered orally, before surgery, every 12 h during successive three-day periods at dose of 400 mg to ten patients hospitalized for prostatic adenoma or for prostatic cancer. On the day of surgery, a 400 mg-last dose was administered. Unchanged norfloxacin was assayed by high performance liquid chromatography with fluorescence detection. The Cmin value was 1.2 +/- 0.77 mg/l. Concurrent norfloxacin concentrations in plasma and epididymal tissue (left and right) were determined, about 4 h after the last drug intake, the epididymal level was 3.4 +/ 1.9 micrograms/g. This value was above the MIC90 for most sensitive organisms. The ratio (+/- SD) of drug concentration in epididymal tissue and in plasma was 3. 74 +/- 2.10 (range 1.66-10.2). The epididymal level of norfloxacin was strongly correlated with, area under curve (p less than 0.001) and plasma concentration (p less than 0.01). PMID- 1881688 TI - [Experimental study on the hepatobiliary kinetics and excretion of temafloxacin. Evidence for production of active metabolites by the rabbit liver]. AB - Temafloxacin is a new fluoroquinolone derivative currently under evaluation. Its hepatobiliary disposition remains undefined as yet. The present study represents an experimental approach to this issue. Six isolated rabbit liver preparations were perfused for three hours with reconstituted and oxygenated blood in a closed circuit. A the onset of the procedures, temafloxacin 10 mg were added to the circulating blood. Both bile and blood were sampled throughout the perfusion time, and liver fragments were taken at the end of the experiments. Temafloxacin levels were measured by HPLC in serum and hepatic tissue, and by both HPLC and microbiological assay in bile. The percentage of drug undergoing hepatic biotransformation appeared to be high, i.e. 58.3%. This finding is substantiated by the comparison of temafloxacin levels in bile, as provided by HPLC and microbiological assay, the latter yielding concentrations twice as high (biliary peak: 33.5 +/- 2.8 micrograms/ml versus 19.3 +/- 3.1 micrograms/ml by HPLC assay) as those obtained by HPLC (p less than 0.05). Consistently, the average amount of temafloxacin excreted into the bile (0-3 h) was, respectively, 92 micrograms (0.9% of the dose) and 204 micrograms (2.0%) as determined by HPLC and microbiological methods (p less than 0.05); this statistically significant difference suggests the presence of active metabolites in bile. The presented results bring out evidence for substantial biotransformation of temafloxacin by Rabbit liver. Extrapolation to other species, however, would be hazardous; further pharmacokinetic studies are needed in order to assess the relevance of these findings in humans. PMID- 1881689 TI - [Effects of the calcium-channel blocker diltiazem on gentamicin-induced nephrotoxicity in rats]. AB - Injection of diltiazem (40 mg/kg/d) to gentamicin (75 mg/kg/d = G 75 or 100 mg/kg/d = G 100) treated rats enhances aminoglycoside-induced nephrotoxicity. As a result of this combination, acute renal failure becomes systematic and is often irreversible. The lesion is of tubular origin and is characterized by a large increase in the urinary N-acetyl-beta-D-glucosaminidase (u-NAG) activity and its NAG-B isoenzyme level. The phenomenon is twice as marked with G 75 (u-NAG x 6.8, NAG-B x 2.2) as with G 100 (u-NAG x 3.1, NAG-B x 1.1). The effect seems to be attenuated if diltiazem is administered as a preventive treatment or in drinking water. As well as its diuretic properties, diltiazem may aggravate the renal toxicity of gentamicin by reducing the proximal tubular availability of calcium. Diltiazem inhibits reabsorption and behaves like a non-competitive inhibitor of calcium. This deficiency favours the proximal tubular binding and the non specific penetration of gentamicin in the cytosol and cellular organelles (microsomes, mitochondria). The tubular toxic symptoms which ensure (inactivation of membranaceous enzyme, reduction of microsomal protein synthesis and ATP level, decreased of solute reabsorptive flux) lead in turn to proximal tubular necrosis and acute renal failure. PMID- 1881690 TI - [Laboratory's controls of antifungal treatment by the fluconazole of the candidiasis in immunocompromised patients]. AB - The use of antifungal drugs in immunocompromised patients impose to the laboratory the control of the efficacy of these therapy. With fluconazole, one of the most recent antifungal agents these control use a special method (Central Research Pfizer) different of those they are used with others antifungals. We have comparatively tested, using MIC technic four broth mediums (High Resolution medium (Oxoid) YMB (Difco) YNB dextrose (Autobac) and Casitone) and three agar mediums (HR, YMA, Casitone) incubated at 28 degrees C for 24 and 48 h. The strains of yeasts are isolated from oro-pharyngeal prelevements on HIV antibody positive patients observed during six to twelve months and eventually treated by fluconazole. Sixty patients are controlled, 33 give one or more positive cultures with 74 strains of C. albicans and four other yeasts. By determination of the MICs with seven different methods we find any resistant strains with the MICs range from 3.12 to 12.5 or 25 micrograms/ml. PMID- 1881691 TI - [Value of the technique of cellular lysis by thermic shock in the isolation of bacteria causing osteoarticular infections]. AB - The purpose of this work is to compare, a conventional technique, for bacterial isolation, with a lysis-centrifugation method using a rapid freezing in liquid nitrogen, followed by decongelation at 37 degrees C for bone and joint samples. The bone and joint specimens were biopsies and punctions (35 cases) or fistula (10 cases). The residual antibiotic activity of the sample was determined using a susceptible strain of Micrococcus luteus and of Staphylococcus epidermidis. Among the 45 samples, 20 were sterile with both methods among which 8 exhibited a residual antibiotic activity which may have contributed to isolation failure. In 12 cases, bacterial isolates were obtained with both methods. Cultures were obtained from 13 samples with the lysis centrifugation method alone. The isolates were 4 Staphylococcus aureus, 8 coagulase-negative Staphylococcus and 1 Acinetobacter sp. These results suggest that the intracellular location of bacteria may be responsible for the negative cultures from bone or joint specimens. PMID- 1881692 TI - [Fixation of Indium111-labeled antifibrin monoclonal antibody on the vegetation in endocarditis: evaluation in a rabbit model]. AB - The uptake of a 111In labelled antifibrin antibody was studied in left ventricle endocarditis on a rabbit model. The immunospecificity of the antibody for the cardiac vegetations is favorable, exhibiting an uptake at least 4 times that of blood, or myocardium. A planar scintigraphy of the opened left ventricle showed a radionuclide imaging of vegetations, according to anatomical lesions. The use of antifibrin monoclonal antibodies could prove helpful to improve the specificity of valvular lesions visualized by echocardiography, or to detect the small vegetations at the early stage of acute endocarditis. PMID- 1881693 TI - [Clostridium difficile: a typing method for epidemiological studies]. AB - One hundred and twenty two strains of Clostridium difficile were studied: 33 strains were isolated from stools of neonates or children, 89 cases of antibiotic associated diarrhea. The strains were identified by biochemical tests and gaz liquid chromatography of the fermentation products. A typing scheme for Clostridium difficile were proposed by using a polyacrylamide gel electrophoresis of whole cell proteins. We studied the correlation between this typing and the serogrouping scheme based on slide agglutination with a rabbit antisera and previously described by Delmee. The serogrouping defines 10 groups, PAGE allows the differentiation of 12 profiles, with a good correlation between the two methods for some serogroups except for the heterogenous serogroup A. PMID- 1881694 TI - [Treatment of acute otitis media: comparative study of efficacy of cefatrizine and amoxicillin-clavulanic acid]. AB - Fourty hospitalized patients (15 children, 25 adults) suffering from acute otitis media have been treated with either cefatrizine or amoxycillin-clavulanic acid. Bacteriological samples were done during surgery by tympanocentesis (N = 33) or by sampling of middle ear fluid specimens (13). H. influenzae was the most common isolate, following by Enterobacteriaceae, S. aureus, P. aeruginosa, and S. pneumoniae. We conclude that these two antibiotics can be used for treatment of acute otitis media in our country even in adults where the order of frequency of bacteria is different from those reported in children. PMID- 1881696 TI - [Relationship between decreased presynaptic inhibition and muscle spasticity in patients with a history of cerebral insult]. AB - Stimulation electromyography was used to study inhibition of the soleus muscle H reflex induced by stimulation of the common peroneal nerve in healthy individuals and in patients who had underwent cerebral apoplexy. Two successive inhibition waves (D1 and D2) were recorded; the first wave demonstrated the development of presynaptic inhibition of group Ia afferent fibers. In post-insult patients the depth of inhibition diminished depending on the degree of the pathologic increase of the tonus of the skeletal musculature. The role of presynaptic inhibition disorders in the pathogenesis of muscle spasticity is discussed. PMID- 1881695 TI - [Randomized study of amoxicillin-clavulanic acid versus amoxicillin-metronidazole combinations in pyogenic infections of dental origin]. AB - Thirty patients, without any valve defect, cardiac malformation or previous antibiotic administration and presenting dental infections, have been treated either with amoxycillin-clavulanic acid or amoxycillin and metronidazole. Aerobic and anaerobic bacteria have been isolated. These infections were due to mixed flora. Nearly one half of anaerobes were Peptostreptococcus, S. milleri and S. sanguis being predominant among aerobes. The species identified were those found in the mouth in the absence of infection becoming as opportunistic flora. The percentage of cures was equivalent in the two groups. the association amoxycillin clavulanic acid seems to be as active as amoxycillin + metronidazole on the microflora isolated from dentogenous pyogenic infections. PMID- 1881697 TI - [Effect of parenteral administration of calcium on calcium content in the brain and spinal cord of parathyroidectomized rats]. AB - The content of calcium in blood, brain, and spinal cord of rats reduced essentially after removal of the parathyroids. Intraperitoneal injection of calcium gluconate normalizes the level of total calcium in blood and brain of parathyroprival rats but, in contrast, increases it in the spinal cord by 34% as compared to the control level. It is presumed that changes of the calcium content in some organs (not accepted as target-organs), in the spinal cord among others, in disorders of the function of the parathyroid glands is consequent not only on hyper- or hypocalciemia. PMID- 1881698 TI - [Serotonin metabolism in the brain of rats with two forms of hereditary arterial hypertension]. AB - Some distinctions were revealed in serotonin metabolism in brain areas in two strains of rats with hereditary arterial hypertension - SHR (spontaneously hypertensive rats) and HSIAH (hereditary stress induced arterial hypertension). These distinctions include regional and qualitative changes of the serotonin concentration, activity of type A monoamine oxidase and tryptophan hydroxylase. PMID- 1881699 TI - [Effect of stepped isovolemic hemodilution on some parameters of systemic and cerebral hemodynamics under normal conditions and in a sharp rise of arterial pressure]. AB - It was demonstrated in rabbit experiments that in decrease of the hematocrit value by more than 10% the increase of arterial pressure induced by intravenous noradrenaline injection and its additional rise are significantly higher than in the controls. In spite of that, the breakthrough of autoregulation of local cerebral blood flow occurred much less frequently, was less pronounced, and attended by significantly less damage to the permeability of the blood-brain barrier to labelled blood albumin. This phenomenon can be explained by the fact that in reduced blood viscosity the pseudoturbulence of its flow, and the hydrodynamic resistance of blood increase due to which it reaches the microcirculatory bed at a lesser pressure than in the controls. The results of the study substantiate the expediency of blood-letting as a therapeutic measure for patients with hypertensive disease, in hypertensive crises also. PMID- 1881700 TI - [Brain electric activity of animals exposed to perfluorocarbon emulsions]. AB - Experiments were conducted on animals with chronically implanted electrodes in the brain to study the frequency composition of its electrical activity in normovolemic replacement of blood with a carbon pertetrafluoride emulsion "Perftoran" (11 rats), and in plethoric intravenous (7 rabbits) and intracerebral (5 rats) injections of this preparation. Marked reactions were encountered in the initial period after Perftoran administration (up to 4-8 hours in transfusions and 0-5 minutes in intravascular and intracerebral infusions). PMID- 1881701 TI - [Autonomic-effector disorders in the restorative period after circulatory arrest of varying duration]. AB - The reactivity of the autonomous nervous system (ANS) was analysed pharmacologically with phenylephrine hydrochloride and D-L-Dopa in experiments on dogs who experienced 1-, 5-, and 10-minute clinical death. In changes of the pronounced character of the postresuscitation damages to the central nervous system, the changes of the ANS differed not only in intensity but also in the trend. Reactivity from sympatho- and parasympathetic types changed in the direction of vegetative equilibrium and atypical reactions. The occurrence of the last named on the first day after 5- and 10-minute clinical death were an absolute prognostic criterion of unfavourable outcome of resuscitation. Disorders of the synthetic capacity of the sympathoadrenal system in increase of the period of circulatory arrest were very important in ANS dysfunction. PMID- 1881702 TI - [Contractile function and some parameters of energy metabolism of the myocardium in the process of adaptation to the effect of moderate continuous stress]. AB - Experiments were conducted on rats to study the dynamics of changes of the heart contractile function (CF) and some indices of myocardial energy metabolism during adaptation to moderate continuous 15-day stress. After 24 hours of stress a complex of shifts typical of an acute stress syndrome (mobilization of CF, reduction of the content of glycogen and creatine phosphate, increase of phosphorylase activity) was recorded. After 5 days of stress the absolute CF value reduced, particularly at rest (doubled), as a consequence of which the relative values of the maximally developing CF on the 5th second of an isometric load induced by compression of the aorta were 1.5 times those in the controls. The content of glycogen and creatine phosphate and the activity of phosphorylase were reduced by 25-30%. After 15 days the CF and the values of myocardial energy metabolism were normalized. Exclusion of the vagal tonus by atropine on the 5th day of stress showed that the low level of CF and reduced phosphorylase activity are not consequent upon heart exhaustion but are regulatory mechanisms. PMID- 1881703 TI - [Various biochemical survival mechanisms in highly-resistant animals]. AB - It was demonstrated in experiments on albino rats subjected to hypoxic hypoxia or hypothermia that highly-resistant animals, accounting for 30% of the population, survive much longer than animals with low and moderate resistance because extreme factors activate in them the system of peroxidase enzymes destroying the peroxides with the liberation of oxygen, which is then included in energy metabolism. PMID- 1881704 TI - [Crush syndrome: etiology and pathogenesis]. PMID- 1881705 TI - [Immunoglobulin antibodies to lysosomal enzymes as a means of proteolysis inhibition in severe blood loss]. AB - Experiments were conducted on rats with massive prolonged blood loss to study the effect of immunoglobulins to lysosomal enzymes in combination with isotonic sodium chloride solution on the values of hemodynamics, oxygen regimen, and acid base balance in the organism. Administration of antibodies to the lysosomal enzymes with an infusion medium leads to a decrease of cathepsin D activity to the initial level. Most probably, diminution of proteolysis is conducive to improvement of circulation. Inhibition of protease activity improves the permeability of vessels and thus facilitates an increase of the volume of circulating plasma, which may be judged from the authentic decrease of the hematocrit and hemoglobin. The oxygen budget and the acid-base balance in the organism are restored more fully. The use of immunoglobulins to lysosomal enzymes prolongs the animals' life. PMID- 1881706 TI - [Therapeutic efficacy of a new antihypoxic agent, ethomerzol, in experimental hemorrhagic shock]. AB - The antishock efficacy of a new antihypoxant ethomerzol was studied in cats with experimental hemorrhagic shock. Ethomerzol raised the therapeutic efficacy of infusion therapy with isotonic sodium chloride solution. It was found that the agent improves systemic hemodynamics and peripheral circulation. On grounds of analysis of the experimental data it is concluded that the inclusion of ethomerzol in the schedule of infusion therapy in hemorrhagic shock is expedient. PMID- 1881707 TI - [Appraisal and significance of individual reactivity, daily and seasonal fluctuations of biorhythms, age, sex, and force and multiplicity factor of mechanical effects in the development and outcomes of the shock process]. AB - Experiments were conducted on 944 rats on two models of traumatic shock (prolonged crushing of soft tissues of the thighs, shock after Cannon). A diagnostic index of the severity of traumatic shock (K) was elaborated which showed in conditional units (from 0 to 9) the relation of changes of the skin electric resistance before and after the trauma. The types of the animals' responses were determined and classified according to this index. In severe shock K varied from 2 to 3.5 (the survival of animals did not exceed 24 hours). In moderately severe shock it ranged between 0.8 and 2 or 3.5 and 9 (the survival period was 2-3 days). In mild shock this index ranged from 0 to 0.5 (survival period was 4-5 days). The authors determined the informative significance of some criteria for complex evaluation of the severity of the shock in experiments. According to this significance, the criteria stand in the following diminishing sequence: force of the mechanical effect, factors of individual reactivity (pronounced K index, duration of phase two of its fluctuations), age (weight), time of day, season, sex. PMID- 1881708 TI - [Effect of dimethyl sulfoxide and dimethyl sulfone on a destructive process in the joints of mice with spontaneous arthritis]. AB - The authors used the blind method for evaluation of the morphological picture of the joints and the level of circulating immune complexes to study the effect of prolonged oral administration of dimethyl sulfoxide (DMSO) and its main metabolite dimethyl sulfone on the development of spontaneous arthritis in 36 Mrl/Mn/lnr female mice. It was found that DMSO and dimethyl sulfone lessen the destructive changes in the joints, while DMSO also inhibits the manifestation of immune disorders, i. e. produces a "basal" effect on the course of spontaneous chronic arthritis in experimental animals. PMID- 1881709 TI - [Role of the destructive phase of regeneration in reparative osteogenesis]. AB - Experiments were conducted on mongrel male rats to study the dependence of the character of maxillary fracture consolidation on the content of osteo-inducing (01) and osteo-inhibiting (I) proteins in the bone tissue as well as the effect of agents intensifying (parathormone) or reducing (methyluracil) the resorption phase of bone regeneration. It is shown that the ratio of OI and I proteins in the bone tissue determines the healing of the fracture according to the type of uncomplicated or slow consolidation in untreated animals, whereas parathormone administration increases the number of animals with uncomplicated consolidation of the fracture and raises the strength of union of the fragments. Methyluracil fails to produce such on effect. It is suggested that improved regeneration of bone in intensification of the phase of resorption is due to more effective excretion of OI proteins from the injured bone tissue. PMID- 1881710 TI - [Content of biological antioxidants and lipid peroxidation in the adrenal cortex in experimental circulatory insufficiency]. AB - Thirteen-week experimental insufficiency in rats causes exhaustion of adrenal cortex function. The number of diene conjugates in the adrenals increased, the alpha-tocopherol level decreased. It is suggested that reduced level of antioxidant protection and the associated activation of lipid peroxidation processes underlie the disorders of adrenal cortex function. PMID- 1881712 TI - [The pancreas as a source of natural diabetogenic factor in alloxan diabetes]. AB - The results of experimental studies bear evidence that the pancreas of healthy animals produces a humoral factor which differs from insulin and prevents the development of alloxan diabetes. The pancreas of diabetic animals loses the above mentioned activity and produces into the blood plasma a natural diabetogenic factor which promotes the development of alloxan diabetes. PMID- 1881711 TI - [Additive effect of repeated impulse air waves on the activity of rat and human hepatic enzymes]. AB - Impulse air waves (IAW) applied in non-destructive and weakly destructive intensities reduced the activity of lysosomal and microsomal enzymes as well as the activity of adenylate cyclase in the liver of laboratory rats. Five times repeated single application of IAW in intensities causing no noticeable biochemical (and morphological) changes led to shifts in the activity of rat hepatic enzymes. IAW which failed to produce a biological effect in humans when applied separately, inhibited noticeably antipyrine biotransformation in volunteers when applied repeatedly 80 times. It is concluded that the action of repeated subthreshold IAW is additive in character. PMID- 1881713 TI - [General pathophysiology of the nervous system]. PMID- 1881714 TI - [Some regularities of gentamicin pharmacokinetics in intranodular and lymphotropic injections]. PMID- 1881715 TI - [Novel methods for modelling unilateral pulmonary edema]. PMID- 1881716 TI - [Mechanisms of development of microcirculatory disorders in patients with stable angina pectoris]. PMID- 1881717 TI - [Change in the level of vasoactive intestinal peptide in the cerebral cortex and hypothalamus and behavioral reactions of rats after frontal lobectomy]. AB - The effect of a change in the level of the vasoactive intestinal peptide (VIP) on the behavior of rats in frontal lobectomy was studied. It was shown by means of the radioimmunological method that damage to the frontal cortex leads to a decrease of the VIP level in the cortex and increase of its content in the hypothalamus on the 9th postoperative day. Daily injection of VIP in small doses into the lateral ventricles of the brain is conducive to more rapid and complete restoration of the conditioned bilateral avoidance reflex and the animals' exploratory behavior under conditions of an "open field" as compared to that in control rats which received a physiological solution. The possibility of using VIP in experimental complex pathogenetic therapy of disturbed functions of the central nervous system is discussed. PMID- 1881718 TI - Dexamethasone therapy in neonatal chronic lung disease: an international placebo controlled trial. Collaborative Dexamethasone Trial Group. AB - In a multicenter trial of steroid therapy for chronic neonatal oxygen dependence, 287 neonates were randomly allocated from around 3 weeks of age, to dexamethasone or placebo. Active treatment significantly reduced the duration of further assisted ventilation among infants who were ventilator dependent at entry (median days for survivors, 11 vs 17.5). There were no statistically significant differences between the total groups of survivors in time receiving supplemental oxygen and length of stay in hospital, although the trend favored the dexamethasone group. Twenty-five infants in each group died prior to hospital discharge; most were ventilator dependent at trial entry. Open treatment with steroids was later given to 18% in the active group and to 43% in the placebo group. There was no evidence of serious side effects; in particular, infection rates were similar in the two groups. PMID- 1881720 TI - Intravenous immunoglobulin therapy for prevention of infection in high-risk premature infants: report of a multicenter, double-blind study. AB - The effectiveness of intravenously administered immunoglobulin (Ig) therapy for prophylaxis of infection was evaluated in high-risk preterm infants. Two hundred thirty-five premature newborns were randomly assigned, in a double-blind controlled trial, to treatment and placebo groups. Thirty-five infants (29%) of the Ig group and 29 (25%) of the placebo group had one or more episodes of certain infection. Thirty infants (25%) of the Ig group and 18 (16%) of the placebo group had one or more episodes of probable infection. No significant differences were observed in the incidence of certain or probable infection in treated and control infants. Nevertheless, among the infants who had one or more certain or probable episodes of infection, more of them belonged to the Ig group than to the placebo group. The possible deleterious effect of the administration of large amounts of polyspecific Ig is discussed. PMID- 1881719 TI - Randomized, double-blind trial of deflazacort versus prednisone in juvenile chronic (or rheumatoid) arthritis: a relatively bone-sparing effect of deflazacort. AB - Thirty-four children with juvenile chronic (rheumatoid) arthritis were recruited to a randomized, double-blind study of deflazacort (an oxazolone derivative of prednisone) vs prednisone. All had been receiving glucocorticoid therapy for at least 1 year and required at least 5 mg/d of prednisolone (usually as 10 mg every 2 days). Thirty-one children completed the study. Bone density trends were measured in the spine by dual photon absorptiometry and in the forearm by single photon quantitative computed tomography at 3-monthly intervals. Trends (velocities) in bone and soft tissue growth were calculated. In the spine, bone growth correlated well with indices of soft tissue growth, but covariance analysis showed a significant advantage (P less than .007) of deflazacort when spinal bone mineral growth was compared to body surface area and weight. In part this was due to a temporary interruption in weight by children receiving deflazacort, whose gain in height was comparable with that of the prednisone group. Some children in both groups improved clinically and showed catch-up growth; in these children relative spinal bone mineral growth velocities were about twice those observed for height and weight. It is concluded that during the first year of deflazacort, their spinal bone mineral content at a level that was appropriate for their height and weight. Further observations are required to establish whether this advantage can be maintained subsequently. The anti inflammatory effects of the two glucocorticoids appeared similar. PMID- 1881721 TI - Do postpartum nursery visits by the primary care provider make a difference? AB - A prospective, randomized, clinical trial was conducted to investigate whether a postpartum visit between a mother and her neonate's future primary care provider combined with telephone access would improve health care utilization, enhance identification of the provider as a source of advice, increase maternal knowledge of infant care, and decrease maternal anxiety and depression. Of 251 mother neonate pairs, 122 were randomized to the control group and 129 to the intervention group. Outcome variables included health care utilization and results of maternal interviews. More mothers in the intervention group made a scheduled clinic visit in the first 30 days (P = .003), were more likely to seek some form of care at the clinic (P = .006), and tried to reach their physician by phone more often than the control group (P less than .001). There were no differences between the groups' emergency room utilization, the percent who received immunizations by 90 days of age, maternal knowledge of infant care, maternal anxiety, or postpartum depression. The intervention succeeded in improving some measures of health care utilization and results suggest that the relationship between the mother and clinician was strengthened. PMID- 1881722 TI - The infant with acute, unexplained, excessive crying. AB - This study describes 56 infants who presented to the Emergency Department of The Children's Hospital of Denver during a 1-year period with an episode of excessive, prolonged crying, without fever and without a cause that was apparent to the parents. The final diagnoses included a broad array of conditions, of which 61% were considered serious. The history provided clues to the final diagnosis in 20% of cases. Physical examination revealed the final diagnosis in 41% and provided clues to the diagnosis in another 13%. Accurate diagnosis requires a thorough physical examination, which should include careful skin inspection underneath all clothing, palpation of all large bones, fluorescein staining of the cornea, eversion of eyelids, rectal examination, retinal examination, and thorough neurologic examination. "Screening" laboratory tests, except for urinalysis and urine culture, were of little help. This study indicates that for those patients in whom the physical examination is not diagnostic, the persistence of excessive crying after the initial examination predicts the presence of a serious cause. Those infants who cease crying before or during the initial assessment are unlikely to have a serious cause. Recommendations for a stepwise assessment are offered. PMID- 1881723 TI - Normative sexual behavior in children. AB - A large-scale, community-based survey was done to assess the frequency of a wide variety of sexual behaviors in normal preadolescent children and to measure the relationship of these behaviors to age, gender, and socioeconomic and family variables. A sample of 880 2- through 12-year-old children screened to exclude those with a history of sexual abuse were rated by their mothers using several questionnaire measures. The frequency of different behaviors varied widely, with more aggressive sexual behaviors and behaviors imitative of adults being rare. Older children (both boys and girls) were less sexual than younger children. Sexuality was found to be related to the level of general behavior problems, as measured by the Achenbach Internalizing and Externalizing T scores and to a measure of family nudity. It was not related to socioeconomic variables. PMID- 1881724 TI - Use of western blot and enzyme-linked immunosorbent assays to assist in the diagnosis of Lyme disease. AB - Without evidence of erythema chronicum migrans, diagnostic confirmation of Lyme disease may be difficult, particularly if there are conflicting laboratory results. Often, for families and physicians, the clinical dilemma is whether fatigue, arthritis/arthralgias, a positive enzyme-linked immunosorbent assay (ELISA), and tick exposure, but no evidence of erythema chronicum migrans, are sufficient to diagnose and treat Lyme disease. Patients with discordant ELISA and Western blot (WB) assay results for Borrelia burgdorferi were studied to determine whether there was sufficient clinical evidence to support a diagnosis of Lyme disease. Of 650 consecutive sera analyzed by ELISA in a laboratory within a 1-year period, 77 were subsequently tested by WB. The clinical data from these patients were then analyzed. The study population was divided into three groups: group 1 (positive ELISA, positive WB), group 2 (positive ELISA, negative WB), and group 3 (negative ELISA, negative WB). Findings included the following: (1) Patients with a strong clinical history of Lyme disease were usually positive by both WB and ELISA (group 1). (2) All patients with erythema chronicum migrans had both positive WB and ELISA tests. (3) Ninety-one percent of group 2 had a rheumatic or inflammatory condition other than Lyme disease. (4) A definite response to antibiotics occurred in 75% of patients wherein both ELISA and WB were positive but in only 11% of cases with a positive ELISA but a negative WB. (5) History of tick exposure and degree of fever were not significantly different among the three serologic groups, and thus they were not diagnostically helpful.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881725 TI - Long-bone fractures in young children: distinguishing accidental injuries from child abuse. AB - While testifying in child abuse cases, physicians have been frustrated by the lawyer who asks, "Doctor, how did this injury happen?" The medical records and radiographs of 215 children younger than the age of 3 with fractures evaluated by a pediatric service during a 5-year period were retrospectively reviewed in an attempt to elucidate the mechanism of childhood fractures. Based on these reviews, two clinicians and two pediatric radiologists rated the likelihood that the fracture was either accidental or due to child abuse. Long-bone fractures were strongly associated with abuse. This report focuses on the 39 children with either humeral or femoral fractures. Fourteen children had humerus fractures. Eleven were considered to be the result of child abuse, and 3 the result of accidents. The latter 3 were supracondylar elbow fractures in children who fell from a tricycle, a rocking horse, or downstairs. Humerus fractures other than supracondylar fractures were all found to be due to abuse. There were 25 femur fractures. Nine were found to be from abuse, 14 were found to be from accidents, and 2 could not be rated. Sixty percent of femur fractions in infants younger than 1 year of age were due to abuse. Although it is taught that femur fractures in young children are inflicted unless proven otherwise, in this study it was found that femur fractures often are accidental and that the femur can be fractured when the running child trips and falls. PMID- 1881726 TI - Perinatal cocaine effects on neonatal stress behavior and performance on the Brazelton Scale. AB - Fifty-two newborns were assessed for the effects of maternal cocaine use on their performance on the Brazelton Neonatal Behavior Assessment Scale and on their stress behaviors during the Brazelton as tapped by the Neonatal Stress Scale. The cocaine-exposed newborns experienced more obstetric complications, had smaller head circumferences, showed more limited habituation abilities on the Brazelton Scale, and exhibited more stress behaviors than control newborns. PMID- 1881728 TI - Long-term mental health effects of a pediatric home care program. AB - The increased survival of youngsters with chronic physical disorders has led to concern about their long-term psychological adjustment. Few data are available on how to reduce the psychological morbidity that occurs in the presence of chronic childhood illness. An earlier report of a randomized controlled trial of a pediatric home care program demonstrated that this program, combining comprehensive biomedical and psychosocial care, reduced the short-term psychological morbidity of those receiving home care. However, data have not previously been available on whether the short-term improvement in adjustment is associated with any long-term benefits. This report presents long-term follow-up data collected 4 1/2 to 5 years after enrollment on 68% of the original sample. After this interval there were even larger differences between the experimental and control groups than those previously observed at 6 months and 1 year. This finding provides strong evidence that a comprehensive family-oriented outreach program for youngsters with chronic physical disorders can have long-term mental health benefits. It should encourage clinicians to develop similar programs and investigators to look for long-term effects of other interventions. PMID- 1881727 TI - Prolactin and cortisol levels in various paroxysmal disorders in childhood. AB - The hormonal response of the anterior pituitary to various epileptic and nonepileptic events in children was studied. Postictal serum prolactin and cortisol levels were measured in 17 children with epilepsy, 23 with febrile seizures, and 10 with syncope or breath-holding spells. The levels were compared with those of 30 children with nonspecific fever, and 23 afebrile children served as control subjects. Significantly higher (P less than .01) prolactin levels (26.5 +/- 3.3 ng/mL, mean +/- SEM) were found in the epileptic group, compared with levels in children with febrile seizures (13.2 +/- 1.0 ng/mL), fever (11.2 +/- 0.9 ng/mL), syncope (7.3 +/- 0.9 ng/mL), and the control group (7.9 +/- 0.6 ng/mL). In contrast, serum cortisol levels were nonspecifically elevated in the epileptics and patients with febrile seizures or fever only. These findings suggest that elevated prolactin levels may be found after epileptic seizures and much less after febrile seizures, but not after breath-holding spells or syncopal events. Cortisol secretion appears to be nonselectively triggered by all stressful events, such as epileptic and febrile seizures, and fever. Elevated prolactin levels (greater than 15 ng/mL) associated with seizures may help in differentiating epileptic from febrile seizures or syncope. PMID- 1881729 TI - Who benefits from a pediatric home care program? AB - Earlier reports of a randomized controlled trial of the Pediatric Home Care (PHC) program for children with chronic physical illness demonstrated overall benefits for the group enrolled in the PHC program. This paper examines which subgroups benefited most (relative to control subjects) and which benefited least from the PHC intervention. Prior to the randomized controlled trial, PHC served those with the most burdensome medical conditions from the families with the fewest coping resources. However, data from the randomized controlled trial (N = 219) show that these were not the subjects who benefited most. Maximal benefit was evident when illness burden was small, but coping resources were low (social, educational, financial, and personal). Analyses of covariance show that subjects in PHC with both low burden and low resources had consistently better outcomes than similar subjects in Standard Care. When the illness burden was similarly low, but resources were more abundant, those in Standard Care appear to have had better outcomes than those in PHC. For those whose illness burden was more severe, the results were mixed. These findings suggest that the conventional priority of allocating existing intervention resources to the medically most burdensome cases may not always be maximally beneficial. Those with less burdensome conditions may derive greater benefit relative to control subjects from an intervention than those with extreme needs. Both medical and social factors should enter into the decision regarding the allocation of scarce resources. PMID- 1881730 TI - Legal proof of child sexual abuse in the absence of physical evidence. AB - Child sexual abuse criminal court cases from a 12-month period were reviewed to determine the frequency and significance of physical evidence in legally "proven" felony cases with penetration. One hundred fifteen consecutive cases were reviewed, and 87 (76%) had resulted in conviction of the perpetrator on felony charges. Charges of vaginal rape were made in 88 cases, and oral and/or anal sodomy in 67 cases. Physical evidence was present in only 23% of all cases that resulted in felony convictions. Felony convictions were obtained in 67 (79%) of 85 cases without physical evidence and in only 20 (67%) of 30 cases with physical evidence. Eight of the 10 cases without physical evidence that did not result in conviction involved victims younger than 7 years of age. Cases involving the youngest victims had a significantly lower conviction rate (12 of 23), despite a very high frequency (13 of 23) of physical evidence (P less than .0005). Physical evidence was neither predictive nor essential for conviction. Successful prosecution, particularly in cases involving the youngest victims, depended on the quality of the verbal evidence and the effectiveness of the child victim's testimony. PMID- 1881731 TI - Informational needs of parents of sick neonates. AB - Sixty-one parents of 43 neonates in a neonatal intensive care unit were interviewed within 3 days of their first conference with the neonatologist to assess their needs for medical information. The conference with the physician and the interview with the investigator were audiotaped. Information given by the physician and information recalled by the parents was categorized and rated by the investigator. The physicians gave very detailed information about diagnosis in 77% of cases whereas 39% of the parents recalled diagnostic information in great detail. Respective percentages for prognosis were 16 and 33; for current management (eg, investigation, therapy), 28 and 66; and for cause of illness, 16 and 18. The statistical significance of the differences between the very detailed information int he physician-parent conferences and in the parent-investigator interviews was, by category, less than .002, less than .041, less than .004, and not significant, respectively. Information in the respective categories was described as "most helpful" by 20%, 67%, 90%, and 8% of parents. All but one of the parents stated that they wanted the whole truth. Physician uncertainty in providing information was significantly associated with severity of illness. It is concluded that while parents wanted information in all categories, they paid most attention to that relating to management. Physician-parent discordances with respect to information about management, diagnosis, and prognosis suggest directions for future investigation of the optimal content of information for parents in this context. PMID- 1881732 TI - Childhood morbidity: comparisons, clusters, and trends. AB - Standard mortality and morbidity data are important but incomplete descriptors of child health. Simple prevalences of individual conditions fail to capture fully the nature of ill health in childhood. More enlightening are comparative prevalences: cross-nationally, in different population subgroups, or as trends over time. A longitudinal perspective that provides information on high-risk states and that the nature of their impact on various aspects of health over time adds another dimension to an understanding of child health needs. A better understanding of the meaning of "health problems" in children and documentation of their distribution in the population will help to tailor better the organization and delivery of preventive, curative, and restorative child health services to child health needs. PMID- 1881733 TI - Rehospitalization for respiratory illness in infants of less than 32 weeks' gestation. AB - All 133 surviving infants of gestational age less than or equal to 32 weeks born July 1, 1985, to June 30, 1986, as well as a socioeconomically matched full-term control group were observed prospectively for 2 years to determine the incidence of rehospitalization for respiratory illness. Perinatal and seasonal factors associated with increased risk for such hospitalizations were also examined. Forty-seven (36%) preterm infants were rehospitalized compared with 3 (2.5%) of 121 term infants (P less than .001). Preterm infants with and without rehospitalization were similar for mean birth weight (1104 +/- 329 g and 1188 +/- 360 g, respectively) and gestational age (28 +/- 2 weeks for both groups); however, infants who were subsequently rehospitalized had required more days of mechanical ventilation, supplemental oxygen therapy, and neonatal intensive care. While a history of bronchopulmonary dysplasia was a risk factor for rehospitalization (45% compared with 25% of those without bronchopulmonary dysplasia, P less than .05), preterm infants with no history of bronchopulmonary dysplasia still showed a 10-fold increase compared with control infants. Among the 43 infants who required no mechanical ventilation beyond the day of birth, 10 (23%) required rehospitalization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881734 TI - Gestational age assessment in preterm neonates weighing less than 1500 grams. AB - Postnatal assessment of gestational age in preterm neonates traditionally has been performed using the methods of Dubowitz and Ballard. This study was designed to determine the accuracy of these methods in a sample of very low birth weight preterm neonates. Dubowitz and Ballard examinations were done on 110 preterm neonates within the first 72 hours of life by a neonatologist masked to the gestational age assessed antenatally. Mean birth weight was 1066 +/- 256 g (SD). These data were compared with gestational age assessments using last menstrual period and best obstetric estimate calculated by an obstetrician unaware of the neonatal examination. Mean gestational age using last menstrual period was 28.3 +/- 2.9 weeks. Mean differences between last menstrual period and Dubowitz/Ballard were -2.8 +/- 2.1 weeks and -2.6 +/- 2.2 weeks, respectively. Results using best obstetric estimate were similar. An ophthalmologist examined lens vessels of 89 neonates. A similar pattern toward overestimation of gestational age interval by Dubowitz/Ballard was seen at each lens vessel grade. The Dubowitz and Ballard examinations are inaccurate methods of assessing gestational age in preterm neonates with birth weights less than 1500 g. PMID- 1881735 TI - Six-year follow-up of early physiotherapy intervention in very low birth weight infants. AB - Eighty very low birth weight infants assigned to neurologically normal or at-risk groups on the basis of a neurodevelopmental score were previously described. Infants were assigned to physiotherapy or control groups, and the effect of physiotherapy was assessed at 1 year. At-risk infants had a significantly lower developmental quotient than the normal group and no beneficial effect of physiotherapy was shown. Of the original 80 subjects, 49 were reassessed at a mean age of 74.7 months. As observed previously, physiotherapy until 1 year did not influence subsequent outcome in either normal or at-risk children. At-risk and normal children had similar mean developmental quotients at 6 years, but the locomotor score of at-risk children was significantly below that of normal children. Cerebral palsy occurred in 6 of 24 at-risk vs 0 of 25 normal subjects (P less than .01) and remedial therapy was recommended in 17 of 24 at-risk subjects vs 6 of 25 normal subjects (P less than .001). These results confirm that the neurodevelopmental score predicts a risk for either cerebral palsy or soft neurological problems, and early physiotherapy is of questionable benefit in preventing such problems. PMID- 1881736 TI - Morbidity estimates of conditions originating in the perinatal period: United States, 1986 through 1987. AB - Morbidity estimates of conditions originating in the perinatal period have not been reported in the United States. Conditions originating in the perinatal period were identified according to the International Classification of Diseases. The National Hospital Discharge Survey provided a weighted, nationally representative sample of newborns discharged each year from short-stay, nonfederal hospitals. From 1986 through 1987, 33.7% of all newborns had at least one nonteratologic perinatal condition. However, 6.8% of all newborns had physiologic jaundice as their only discharge diagnosis. Nonphysiologic jaundice was diagnosed in 4.4%, maternal causes of perinatal morbidity in 3.1%, birth trauma in 2.5%, fetal distress in 2.3%, birth asphyxia in 2.1%, and infections specific to the perinatal period in 2.0% of all newborn discharges. The average hospital stay for all newborns was 3.5 days, but it was 5.3 days for newborns with at least one nonteratologic perinatal condition and 2.6 for newborns discharged without a morbid condition. This study provides nationally representative estimates of perinatal morbidity useful for comparisons with smaller hospital-based samples. In addition, the study provides estimates of the public health impact of these conditions in terms of hospital stay days. PMID- 1881737 TI - Social acceptability of methylphenidate and behavior modification for treating attention deficit hyperactivity disorder. AB - The social acceptability of methylphenidate, behavior modification, and methylphenidate plus behavior modification was evaluated. Fifty mothers of children with attention deficit hyperactivity disorder (ADHD) and 50 control mothers, along with 21 children with ADHD and 20 control children, read a case vignette of an 8-year-old boy with ADHD and descriptions of the three treatment conditions. Subjects then rated the acceptability of each treatment. The mothers of children with ADHD were reassessed 3.5 months later, after experience with interventions for their children. Both ADHD and control families rated behavior modification as the most acceptable, methylphenidate as least acceptable, and the combined condition intermediate between the other two. At follow-up, there was a significant improvement in the acceptability of methylphenidate and the combined condition. The increased acceptability of methylphenidate at follow-up was related to increases in parents' knowledge about ADHD but not to the significant improvements that occurred in the children's hyperactive behavior. PMID- 1881738 TI - Acute otitis media in human immunodeficiency virus-infected children. AB - To evaluate the occurrence and outcome of acute otitis media (AOM) in human immunodeficiency virus (HIV)-infected children, a prospective comparative cohort study was performed. Twenty-seven HIV-infected children were individually matched with paired control subjects and followed up for 543 months (mean 19.4 +/- 11). Data collected were evaluated considering HIV-infected children both as a whole and as P1 and P2 patients according to Centers for Disease Control classification. During the observation period, 46 episodes of AOM were diagnosed in 15 HIV patients and 22 in 16 control children: 11 P1 had 27 AOM episodes vs 17 in 13 control children; 6 P2 had 19 AOM episodes vs 5 in 4 control children. Human immunodeficiency virus infection does not seem to modify the occurrence of AOM. Recurrent AOM (3 or more episodes in 6 months) was, however, significantly more common in P2 children. Amoxicillin, to which the bacteria isolated in P2 children were sensitive in vitro, cured 33 of 46 episodes in HIV-infected children compared with 20 of 22 in control children. Cure rate was similar in P1 children compared with control children but was significantly lower in P2 versus control children (47.3% vs 100%). Reasons for higher occurrence of failures in P2 children remain to be investigated. PMID- 1881740 TI - Factors influencing the epidemiology of Helicobacter pylori infection in children. AB - The epidemiology of Helicobacter pylori infection was studied in 245 healthy children (between 3 and 20 years of age) who presented for day surgery at Arkansas Children's Hospital. H pylori infection was identified serologically using an enzyme-linked immunosorbent assay to detect the presence of IgG against the high molecular weight, cell-associated antigens of H pylori. Demographic information collected included age, gender, race, family income, type of housing, location of housing, water supply, health status, upper gastrointestinal symptoms, and keeping pets. One hundred eighty-nine white children and 56 black children were studied; 139 were boys and 106 were girls. The data were analyzed by logistic regression analysis. H pylori infection increased significantly with age (P less than .05). The frequency of H pylori infection was higher in blacks than whites (P less than .01), and this difference remained after adjusting for age, gender, and family income. Family income was used as a measure of socioeconomic class and was an important factor related to infection; the rate of acquisition of H pylori in those children with family income less than +5000/year was twice that of those with incomes greater than +75,000/year (P less than .001). There were no significant differences in H pylori infection related to gender, type of housing, location of housing, or source of water supply. It is concluded that the rate of acquisition of H pylori infection increases with age, is higher in blacks than whites, and is inversely related to socioeconomic class. PMID- 1881739 TI - Tap water burn prevention: the effect of legislation. AB - Five years after a 1983 Washington State law required new water heaters to be preset at 49 degrees C (120 degrees F), 77% of homes (84% of homes with postlaw and 70% of homes with prelaw water heaters) had tap water temperatures of less than 54 degrees C. In 1977, 80% of homes had tap water temperatures greater than 54 degrees C. Mean temperature in 1988 was 50 degrees C compared with 61 degrees C in 1977. Both changes were significant compared with 1977 temperatures. Few people increased their heater temperature after installation. Eighteen burn victims were identified from July 1979 through May 1988, for an average admission rate of 2.4 per year, compared with 5.5 per year in the 1970s. Compared with the 1970s, total body surface area burned, mortality, grafting, scarring, and length of hospital stay were all reduced, while the likelihood that scald burns were the result of child abuse increased to 50%. Both education campaigns and legislation have resulted in significantly safer water temperatures. Further, this change seems to have resulted in a reduction in frequency, morbidity, and mortality of tap water burn injuries in children. Lower water heater settings proved acceptable to the consumer. PMID- 1881741 TI - Neurologic outcome after electroencephalographically proven neonatal seizures. AB - Infants in whom neonatal seizures were confirmed by randomly recorded ictal electroencephalographic (EEG) tracings were retrospectively examined to determine their global neurologic outcome and the specific frequency of epilepsy, development delay, and cerebral palsy. Perinatal and postnatal clinical and EEG variables were also examined for their relevance to the neurologic outcome. Forty infants with EEG documented seizures of diverse etiologies were studied. The 27 survivors were followed up at a mean of 31 months. The outcome was unfavorable in 70%. The rate of epilepsy was 56%, of developmental delay 67%, and of cerebral palsy 63%. The etiology of seizures was an important factor influencing the outcome. Other clinical factors that showed a significant relationship with global or specific aspects of the neurologic outcome included the age at the onset of seizures, birth weight, and neurologic examination results. The EEG parameters that significantly predicted the neurologic outcome were interictal EEG background, increased seizure frequency, and decreased seizure duration. PMID- 1881742 TI - Critical limits for emergency clinician notification at United States children's hospitals. AB - Critical results demand rapid patient evaluation, possibly followed by life saving intervention. A national survey of children's hospitals determined the critical limits used for emergency notification of critical laboratory results. Mean low and high critical limits for children for the tests listed most frequently were as follows (millimoles per liter): glucose, 2.6 and 24.7; potassium, 2.8 and 6.4; calcium, 1.62 and 3.17; and sodium 121 and 156. For newborns, significantly different (P less than .01) critical limits were glucose, 1.8 and 18.2; and potassium, 7.8. Hematology mean critical limits for children included hemoglobin, 69 and 208 g/L; platelets, 53 and 916 x 10(9)/L; hematocrit, 0.20 and 0.62 L/L; and white blood cell counts, 2.1 and 42.9 x 10(9)/L. Critical limits for pH were 7.21 and 7.59; for PCO2, 21 and 66 mm Hg; and for PO2, 45 and 124 mm Hg. Important qualitative critical results included blasts on the blood smear and abnormal cerebrospinal fluid findings. In comparison with other medical centers, children's hospitals maintained tighter critical limits for surveillance of renal function, hemostasis dysfunction, and newborn hypokalemia. Use of these results to eliminate outliers can help reduce unnecessary statim notification and improve resource utilization for the acute diagnosis and treatment of critically ill newborns and children. PMID- 1881743 TI - Immunogenicity of subcutaneous versus intramuscular Oka/Merck varicella vaccination in healthy children. AB - To compare the immunogenicity and safety of varicella vaccine by either subcutaneous or intramuscular injection, 166 healthy children aged 12 months to 10 years old who had no prior history of varicella were enrolled from two pediatric practices and randomly assigned to receive 0.5 mL of a single lot of varicella vaccine. Sera from the day of and 6 weeks postvaccination were tested for varicella antibody by gpELISA. Parents recorded clinical events occurring in the 6 weeks following vaccination. In the 132 evaluable children, the mean prevaccination titer was 0.3 gpELISA units for both groups. Sixty-three (97%) of the 65 receiving varicella vaccine by the subcutaneous route seroconverted compared with 67 (100%) of 67 immunized intramuscularly. Postvaccination geometric mean titer in the subcutaneous group was 6.9 +/- 7.0 gpELISA units and did not differ significantly from the geometric mean titer of 10.5 +/- 4.4 in the intramuscular group. Varicella vaccine was generally well tolerated by either route; 21% of both groups complained of reactions at the injection site and 7% had a varicella-like rash. Although varicella vaccine is recommended to be given subcutaneously, the results of this study indicate that inadvertent intramuscular administration of varicella vaccine is not reason for revaccination. PMID- 1881744 TI - Sticks and stones may break my bones ... reasoning about illness causality and body functioning in children who have a chronic illness. AB - Children's concepts about illness causality and bodily functioning change in a predictable way with advancing age. Differences in the understanding of these concepts in healthy children vs children with a chronic illness have not been clearly delineated. This study included 49 children with a seizure disorder, 47 children with an orthopaedic condition, and 96 healthy children, all with normal intelligence and ranging in age from 5 to 16 years. It demonstrates systematic differences in children's general reasoning skills and in their understanding of concepts about illness causality and bodily functioning, as a function of their age and experience of illness. At all ages, children who had a condition with orthopaedic involvement reported less sophisticated general reasoning and concepts about illness than did healthy children; children with a seizure disorder reported similar general reasoning skills to those of healthy children, but considerably less sophisticated concepts about illness. Children's concepts about body functioning did not differ as a function of the presence of a chronic illness. When their different levels of general cognitive reasoning were statistically controlled, children with a chronic illness had somewhat more sophisticated concepts about bodily functioning than did healthy children. Differences in conceptual development among children with different types of illnesses lead to interesting speculations with regard to the effects of particular illness characteristics on children's cognitive development. PMID- 1881746 TI - Household magnetic fields and childhood leukemia: a critical analysis. PMID- 1881745 TI - Can adolescent suicide attempters be distinguished from at-risk adolescents? AB - Psychiatric disorders, psychosocial dysfunction, family pathology, and environmental stressors are thought to be risk factors for adolescent suicide attempts. Variables from each of these categories were examined, by means of a structured interview and questionnaires, to determine whether a group of 21 adolescent suicide attempters could be differentiated from a group of 34 normal control subjects and a group of 15 at-risk adolescents (teenagers with known risk factors but without recent suicide attempt). The attempters differed significantly from control subjects on a large number of variables, particularly in the areas of substance abuse, depression, self-image, interpersonal relationships, communication patterns, family support, and problem behaviors. Only three items--the Beck Hopelessness Scale score, the SCL-90-R Positive Symptom Distress Index, and a history of suicidal ideation--differentiated the attempters from the at-risk adolescents. A discriminant analysis revealed that hopelessness and suicidal ideation were able to identify 93% of the suicide attempters. PMID- 1881747 TI - Can adolescent suicide attempters be distinguished from at-risk adolescents? PMID- 1881748 TI - Interpreting the notion of "nonbeneficial". PMID- 1881749 TI - American Academy of Pediatrics Committee on Sports Medicine and Fitness: Human immunodeficiency virus [acquired immunodeficiency syndrome (AIDS) virus] in the athletic setting. PMID- 1881751 TI - American Academy of Pediatrics Task Force of Pediatric AIDS. Education of children with human immunodeficiency virus infection. PMID- 1881750 TI - American Academy of Pediatrics Committee on Early Childhood, Adoption & Dependent Care: Initial medical evaluation of an adopted child. PMID- 1881752 TI - American Academy of Pediatrics Committee on School Health. School health assessments. PMID- 1881753 TI - American Academy of Pediatrics Committee on Injury and Poison Prevention. Children and fireworks. PMID- 1881754 TI - American Academy of Pediatrics Committee on Injury and Poison Prevention. The 55 miles per hour maximum speed limit. PMID- 1881755 TI - Sucrose as an analgesic for newborn infants. PMID- 1881756 TI - Use and misuse of oral therapy in diarrhea. PMID- 1881757 TI - A new clue to clavicular fracture in newborn infants? PMID- 1881759 TI - Ricelyte advertising. PMID- 1881758 TI - HIV screening in pregnancy. PMID- 1881760 TI - 'Ivory Tower' fellowship statement challenged. PMID- 1881761 TI - Discrimination of second-format-like frequency transitions. AB - Discrimination of two types of simulated single-second-format frequency transitions was studied, transitions where members of a stimulus set shared the same onset frequency and transitions where stimuli of a set shared the same offset frequency. Experiment 1 employed an adaptive procedure to measure just noticeable differences for transitions that increased in frequency. Experiment 2 obtained complete psychometric functions, based on a three-interval, forced choice procedure, for transitions that either increased or decreased in frequency. In both experiments, better discrimination occurred for longer stimuli, measured in hertz/millisecond, and for transitions that shared the same onset frequency. There were no differences, in Experiment 2, between discrimination of rising and falling transitions. Results are considered from several theoretical perspectives. PMID- 1881763 TI - Processing of Kanji and Kana characters within Japanese words. AB - Two experiments were conducted to examine the temporal relationship between whole word and character processing in Japanese. Two kinds of Japanese script were used as stimuli: Kanji, an ideographic script, and Kana, a syllabic script. In Experiment 1, Kanji word processing and Kanji character processing were examined using a successive visual comparison task. The whole-word advantage (Marmurek, 1986) was not found. In Experiment 2, Kana words and characters were used. As in Experiment 1, no whole-word advantage was found. The absence of the whole-word advantage is attributed to the fact that Kanji and Kana characters represent higher level units of processing than alphabetic letters. The difference between word and nonword processing was shown by manipulations of the visual similarity and the homophony between stimuli presented successively. Visual similarity affected both words and nonwords, whereas homophony affected words only. PMID- 1881762 TI - Visual field effects in the discrimination of sine-wave gratings. AB - The time needed to decide whether the second of two successively presented sinusoidal gratings was of a higher or lower spatial frequency than the first was measured for spatial frequencies of 1, 2, 4, 8, and 12 cycles per degree (cpd) presented in either the left visual field (LVF) or right visual field (RVF). A LVF advantage was found for discriminating within the low-spatial-frequency range (i.e., 1 and 2 cpd), whereas a RVF advantage was found for discriminating within the high-spatial-frequency range (i.e., 4-12 cpd). These findings support the conclusion that hemispheric asymmetries in the processing of gratings arise when comparisons are made between the output of spatial-frequency channels. PMID- 1881764 TI - Perceptual adjustments on representations of familiar patterns: change over time and relational features. AB - Subjects classified individual stimuli as exact copies or as distortions of previously viewed prototype letters. Perceptual adjustments were induced by the presence of difficult (subtle) distortions within the stimulus set. In Experiment 1, subjects initially made feature-based adjustments, and, with experience, adjustments became identity-based. Decisional adjustments also occurred. A similar change over time was obtained in Experiment 2; in addition, the feature based adjustments could not be explained by overall similarity between letters. Experiment 3 indicated that feature-based adjustments can be long lasting under appropriate circumstances. Experiment 4 indicated that the relevant features are not functionally independent parts of letters, but rather relations between neighboring parts. The results are consistent with the idea that adjustments can change between levels over time, and that the adjusted features are relational in nature. PMID- 1881765 TI - Stimulus context and absolute magnitude estimation: a study of individual differences. AB - The effect of stimulus context on absolute-magnitude-estimation (AME) judgments was examined by determining whether the loudness judgment of a tone is influenced by the intensities of other tones presented within the session. A group of 18 subjects was tested in separate sessions in which they judged stimuli within either a low (10-60 dB SL) or a high (40-90 dB SL) range of intensities. Examination of the results of individual subjects revealed that judgments of stimuli common to the two ranges were, in most subjects, unaffected or only slightly affected by the position of the range. The judgments of 2 subjects who failed to follow the instructions, however, showed very large context effects due to changing the stimulus range. The results of a second experiment, in which 22 subjects judged the loudness of tones within either a narrow (35-65 dB SL) or a wide (20-80 dB SL) range, revealed that, in all but 1 subject, the width of the range had no systematic effect on the loudness judgments of stimuli common to both ranges. This was also true 1 month later when 16 of the subjects returned to the laboratory to judge the loudness of tones within an even wider range of 10-90 dB SL. It was concluded that AME judgments are relatively insensitive to the potential biasing influences of stimulus context. PMID- 1881766 TI - The influence of parafoveal preprocessing and linguistic context on the optimal landing position effect. AB - Several experiments have shown the existence of an optimal landing position effect during isolated word recognition as well as during text reading; both the probability of refixating the test word and the gaze duration are smaller if the eye first fixates near the center of the word than if the eye first fixates other positions in the word. However, recent data indicate that the optimal landing position effect is weakened under normal reading conditions, when words are included in texts. The purpose of the present experiment was to test whether parafoveal preprocessing or linguistic context specific to the text reading situation could be responsible for this weakening. With a paradigm that approximates normal reading, albeit in a somewhat slower manner, it was shown that although the possibility of preprocessing words in parafoveal vision and of predicting them from preceding context globally affected refixation probability and gaze duration on the word, this did not strongly affect the optimal landing position effect. Since the global effects of these factors were comparable to those found by other authors in normal reading, it was concluded that the weakening of the optimal landing position effect during text reading results from the influence of other factors peculiar to this situation. Hypotheses are proposed as explanations of the effects of the manipulated factors on oculomotor behavior. PMID- 1881767 TI - The effect of loading on position sense in the tongue. AB - The position sense of the tongue and aftereffects on the position sense subsequent to loading were directly investigated. Nine subjects judged the straightahead with the tongue before and after straining laterally with the tongue against the horizontal force induced by a 29.5-g weight. Two of these subjects also participated in the experiment after the surface of the tongue had been anesthetized. Prior loading of the tongue biased the subjects' subsequent judgment of the straight-ahead; following loading, the tongue was placed farther in the direction of the previous effort. The results are discussed with reference to postcontraction effects from experiments on loading the limb and eye. PMID- 1881768 TI - Two-stage model for order discrimination. AB - Ulrich (1987), exploring the shapes of psychometric functions obtained in the ternary-response paradigm, indicated several inconsistencies between observed and predicted relationships providing evidence against most popular models of temporal-order judgment. In this paper, a new model is presented. It assumes that there are two mechanisms involved in the order discrimination task: one is responsible for the recognition of whether or not the stimuli are successive, and the second is able to determine their order. The model was tested using Allan's (1975a, 1975b) and Ulrich's (1987) data; the model predictions were found to be consistent with the experimental results. PMID- 1881770 TI - Visual selection of features and objects: is location special? A reinterpretation of Nissen's (1985) findings. AB - Nissen (1985) compared selection by location with selection by color or shape in partial-report experiments. Her analysis of response contingencies when a target was defined in terms of one attribute (location, color, or shape), and when the task was to report the two remaining attributes, suggested a special role for selection by location: It appeared that cross-referencing between color and shape was mediated by location. An alternative interpretation is developed here: The findings are explained by a theory of attention (Bundesen, 1990), in which selection by location is treated on a par with selection by color or shape. PMID- 1881769 TI - A further test of the superposition model for the redundant-signals effect in bimodal detection. AB - The superposition model proposed by Schwarz (1989) to account for the redundant signals effect in a bimodal detection task with visual and auditory signals is tested further. It is shown that the model does not fit the observed standard deviations reported by Miller (1986) if the residual (motor) component is assumed to be independent of the waiting time. PMID- 1881771 TI - Marginalisation of mental handicap branch decried. PMID- 1881772 TI - A faint chorus of approval. PMID- 1881774 TI - Ear peace. PMID- 1881773 TI - Local currency. PMID- 1881775 TI - Trusting to luck? PMID- 1881776 TI - A model service. PMID- 1881777 TI - Caring concerns. PMID- 1881778 TI - Nurses and the media. Blowing the trumpet. PMID- 1881779 TI - Nurses and the media. Careful what you say. PMID- 1881780 TI - Resuscitation decisions. PMID- 1881781 TI - Nurses and the media. On the airwaves. PMID- 1881782 TI - A grass-roots approach. PMID- 1881784 TI - Deals on meals. PMID- 1881783 TI - Attack on anxiety. PMID- 1881785 TI - Primary nursing--looking forward. PMID- 1881786 TI - On the road--nice set of wheels. PMID- 1881787 TI - Organisation and stress among mental nurses. PMID- 1881788 TI - Crisis intervention and psychiatric referral. PMID- 1881790 TI - Arts in action. Lessons in creativity. PMID- 1881789 TI - Gender and title-related fears about therapists. PMID- 1881791 TI - Mental handicap nursing. Autism--breaking through the barriers. PMID- 1881792 TI - Mental handicap nursing. Autism--help for the family. PMID- 1881794 TI - Beyond belief? PMID- 1881793 TI - Mental handicap nursing. Autism--a change for progress. PMID- 1881796 TI - Bone graft. PMID- 1881795 TI - Contraception concerns. PMID- 1881797 TI - Sex and sensibility. PMID- 1881798 TI - Danish liaisons. PMID- 1881799 TI - Waspish Winterton. PMID- 1881800 TI - Needs of the carer. All in a day's work. PMID- 1881801 TI - Needs of the carer. Time to let go. PMID- 1881802 TI - The charter for users of nursing/residential homes. PMID- 1881804 TI - Familiarity breeds content. PMID- 1881803 TI - Revising routines. PMID- 1881805 TI - The forgotten children. PMID- 1881806 TI - No place for a holiday. PMID- 1881807 TI - Study methods. Freedom to learn. PMID- 1881808 TI - Study methods. A personal contract. PMID- 1881809 TI - Nursing and the law. First aid law. PMID- 1881810 TI - Breast cancer. A place for women. PMID- 1881811 TI - Breast cancer. Hope and charity. PMID- 1881812 TI - Midwives' Journal. Work and pregnancy. PMID- 1881814 TI - Midwives' Journal. Conference know-how. PMID- 1881813 TI - Midwives' Journal. Repairing the tear. PMID- 1881815 TI - Salivary fluoride concentrations in children with various systemic fluoride exposures. AB - Parotid ductal saliva fluoride concentrations were determined as an indication of baseline plasma fluoride levels in three groups of children. Group I had been exposed to drinking water containing less than 0.1 ppm F and had not received fluoride supplements. Group II had consumed optimally fluoridated water (1 ppm) since infancy. Group III had consumed water with less than 0.1 ppm F but had received a daily fluoride supplement for at least two years. The mean salivary fluoride concentrations in Groups II and III were significantly higher than Group I, but were not significantly different from each other. The findings suggest that peak plasma fluoride concentrations achieved following a daily fluoride supplement dose are higher than previously thought. PMID- 1881816 TI - Pseudohypoparathyroidism: case report. AB - A patient with pseudohypoparathyroidism is presented. The phenotypic appearance, known as Albright heredity osteodystrophy includes: short stature, round face, brachydactylia, and ectopic calcifications in the soft tissues. Dental manifestations reported in the literature are enamel hypoplasia, hypodontia, malformed roots, enlarged pulp chambers, microdontia, and pulp calcifications. Additional findings in this case are ankylosis and an enlarged frontal sinus. The delayed diagnosis of pseudohypoparathyroidism with the early presentation of multiple dental anomalies is discussed. PMID- 1881817 TI - Tissue-space emphysema, tissue necrosis, and infection following use of compressed air during pulp therapy: case report. AB - The intraoperative development of tissue-space emphysema in a child undergoing restorative treatment under general anesthesia is presented. Emphysema development seems to be concomitant with the use of compressed air around patent root canals, complicated by tissue destruction due to movement of canal irrigants/medicaments into the periapical tissues and by secondary infection. Several recommendations for the prevention of tissue-space emphysema are presented including the use of a rubber dam, judicious use of compressed air, and maintenance of canal irrigants and medicaments within the root canal. Treatment recommendations vary from palliative care with follow up in cases of facial emphysema to immediate medical attention in cases of pharyngeal or mediastinal emphysema. PMID- 1881818 TI - An aid to stop thumb sucking: the "Bluegrass" appliance. AB - A nonpunitive fixed appliance utilizing a Teflon (E.I. du Pont de Nemours and Co., Inc., Wilmington, DE) roller is described. The appliance is used in conjunction with a program of positive reinforcement in managing thumb sucking in children 7-13 years of age. It has been used successfully in 24 children, with no cases requiring reinsertion. PMID- 1881819 TI - Well-baby dental examinations: a survey of preschool children's oral health. AB - Well-baby dental visits provide early prevention and detection of dental disease for the infant and preschool child. A survey of the dental records of 379 preschool children from the ages of 6 months to 4.5 years were reviewed from a population of military family dependents. The caries activity of this population was found to be 8.9%, with a dft of 0.25. Nursing caries was clinically definable in 5.3% of the children, accounting for 58.8% of all reported caries. Malocclusion occurred in 6.3%, with anterior open bite and posterior crossbite found most commonly. No soft tissue pathology was noted. Evidence of previous dental trauma to the maxillary incisors with crown discoloration was found in 2.9%. These early dental visits provide a pleasant introduction to dental oral health and prevention for both parents and children. Early dental examinations should focus the parent's attention on the child's future oral health and provide an understanding of the causes of nursing caries. PMID- 1881820 TI - An update in pediatric seizure disorders. AB - Recent advances in knowledge of pediatric seizure disorders, including classification of seizure types and febrile convulsions, have been the topics of major symposia. In light of these recent developments, an in-depth review is presented to aid the pediatric dentist in the treatment of these children. PMID- 1881822 TI - Parental attitudes toward behavior management techniques used in pediatric dentistry. AB - Previous studies evaluating parents' attitudes toward behavior management techniques used in pediatric dentistry suggest that parental attitudes are generally negative. The purpose of this study was to reexamine this issue by comparing the effect of prior explanation on parental acceptance of eight behavior management techniques. Videotaped segments were made of children's dental appointments containing examples of eight behavior management techniques. One group of 40 parents viewed a videotape which provided no explanation for each technique before it was shown. Another group of 40 parents viewed a videotape which provided no explanation of the techniques. The parents then were asked to rate the acceptability of each technique using a visual analogue scale. Results indicated that the informed parents were significantly more accepting of behavior management techniques than the uninformed parents but both groups were generally positive about the techniques studied. Further, parents reporting greater stress were less accepting of the techniques studied. PMID- 1881821 TI - Comparison of ultrasonic and mechanical cleaning of primary root canals using a novel radiometric method. AB - Although ultrasound is employed increasingly as an adjunct to biomechanical preparation in clinical endodontics for adult teeth, there have been no previous investigation of this technique for primary teeth. This investigation studied the efficacy of ultrasonication compared with mechanical cleaning in primary root canals using a novel radiometric method. The results indicated that in multiple rooted teeth, ultrasonication with an endosonic file for 3 min was able to remove 81.1% of inoculated bacteria, compared with only 65.2% using conventional filing. A combination of mechanical filing followed by ultrasonication produced the best results, with greater than 95% bacteria removed. The results show that ultrasonication may be useful for primary teeth endodontics. PMID- 1881823 TI - Treatment and retention of a mandibular arch telescoped within the maxillary arch: case report. AB - A patient in the early mixed dentition was experiencing "difficulty in eating." The right mandibular posterior teeth were telescoped within the maxillary arch. The mandibular midline deviated to the left of the maxillary midline. With the midlines aligned, posterior occlusion was minimal. By activating a lingual arch, the mandibular arch width was increased to establish a posterior occlusion. Also, the lingual arch was used as a retainer. The posterior occlusion remained stable throughout the mixed dentition. An unexpected second phase of treatment was indicated in the permanent dentition because the maxillary right first and second premolars and the maxillary right second molar were completely buccal to the mandibular teeth. Successful treatment was accomplished in spite of broken appliances and noncompliance. PMID- 1881824 TI - Unusual multiple natal teeth: case report. AB - An 18-month-old Japanese boy with multiple natal teeth was examined. Fourteen hard structures were reported to have been present at birth at the regions of the anterior teeth and first primary molars in both jaws. The structures were excessively mobile and 11 of the structures had exfoliated successively since 5 months of age. The three structures remaining at the regions of the first primary molars had bonelike appearance and color, and were smaller in overall dimension than the corresponding primary teeth. Radiographic examinations showed that the structures had neither roots nor pulp chambers and their radiopacity corresponded to that of mandibular bone. Furthermore, there were no permanent successors except for the upper central incisors and left lateral incisor at the regions where the structures were situated. Histological examinations revealed that the specimens consisted of dentin with tubular structure, osteodentin-like structure, and cementumlike structure. PMID- 1881826 TI - Decline in salivary S. mutans levels in children who have received short-term antibiotic therapy. PMID- 1881825 TI - Natal primary molar: case report. AB - The case of an immature natal maxillary first primary molar is reported. Natal molars are rare occurrences, the present instance being only the eighteenth reported case. Clinical and histologic examination revealed that the tooth was rootless, incompletely mineralized, and acutely inflamed. Subsequent radiographs showed that the tooth was actually the primary first molar. PMID- 1881827 TI - [New antiplatelet drugs in coronary heart disease]. PMID- 1881828 TI - [The effect of aminophylline on plasma oxypurines in patients with bronchial asthma or cor pulmonale]. AB - The effect of aminophylline administered intravenously in dose 250 mg on plasma oxypurines (hypoxanthine and xanthine) concentration as well as on plasma adenosine deaminase activity and plasma AMP deaminase activity was studied in 17 patients with bronchial asthma or chronic cor pulmonale. Initial plasma oxypurines concentration was 47.5 +/- 10.4 mumol/l and one hour after aminophylline administration decreased significantly (p less than 0.001) to the value 40.3 +/- 8.8 mumol/l. Plasma adenosine deaminase activity increased significantly from 4.74 +/- 2.3 IU to 6.9 +/- 2.77 IU (p less than 0.01), while plasma AMP deaminase activity did not change. The above results suggest indirectly that intravenous administration of aminophylline decreases serum adenosine concentration in studied patients. PMID- 1881829 TI - [Treatment of respiratory tract infections with pefloxacin]. AB - Pefloxacin, a 4-quinolone derivative, was administered in the dose of 800-1200 mg for the mean of 12 days to 24 patients with respiratory tract infection complicating chronic bronchial asthma or chronic obstructive lung disease. Patients with positive sputum culture and bacteria sensitive to pefloxacin were included in the study. Total eradication of the offending microorganisms was achieved in 54% of patients, and partial--in the next 20%. A poor efficacy of pefloxacin against Streptococcus species has been confirmed. In a few cases we have observed the development of resistance of isolated bacteria to pefloxacin during the course of treatment. PMID- 1881830 TI - [Evaluation of conservative treatment for Graves-Basedow disease depending on the clinical severity of thyrotoxicosis, blood group (ABO) and HLA A1, B8 antigens]. AB - The purpose of the study was to determine whether such factors as: initial exacerbation of thyrotoxicosis, blood group (ABO) and the presence of HLA A1, B8 antigens have an influence on the effectiveness of the conservative treatment of thyrotoxicosis in Graves-Basedow disease (G-B disease). Studies were carried out in two groups of 32 women each with G-B disease. The patients in group I were 28 61 years of age, in whom euthyroid state lasting at least 5 years was attained after treatment with methimazole on average over a 15.4 month cycle. The age of the patients in group II was 27-61 years, in whom at least one relapse occurred in 5-year follow-up. The groups of patients did not differ significantly in the clinical exacerbation of thyrotoxicosis measured in the scale of Zgliczynski. The frequencies of occurrence of the particular clinical symptoms of thyrotoxicosis did not differ in both groups, except diarrhoea with occurred significantly more frequently in women of group II (47%) in comparison with group I (15.6%). No characteristic differences were found between both groups in the occurrence of blood group O, A, B, AB and antigen HLA A1. Statistically significant difference was found in the occurrence of antigen HLA B8 and phenotype HLA A1 B8, both between the patient groups and control. Their influence expressed by odds ratio OR = 3 indicated that the chances of effective conservative treatment for the patients in group II were three times smaller than for those in group I. PMID- 1881831 TI - [Evaluation of verapamil's effect on the circulation in angina pectoris]. AB - The studies concerned fifteen men with a stable angina pectoris--confirmed by an exercise test and coronarography--but with no heart failure or hypertension. They were randomly tested in a double blind method in which cardiovascular system was checked by means of rheographic-cardiography each fortnight after alternate administration of the placebo and verapamil [3 x 120 mg/24 hr]. After verapamil significant lowering of blood pressure and significant decrease of heart rate were found. Rheographic-cardiographic indices of cardias performance: RE time, REc time relation to heart rate, E dz/dt, E dz/dt relation to changes in arterial blood pressure, Heather index, modified Heather index, RE/EX and LVET did not show changes statistically significant. Neither was the change of the index of left ventricle heart failure observed. The only real change was the lengthening of the EX period--depending on the afterload. We can conclude that in patients with a stable angina pectoris the administration of 3 x 120 mg of verapamil does not diminish cardiac performance. PMID- 1881832 TI - [Effect of hypotensive treatment on renal function in patients with pseudo hypertension]. AB - Osler's maneuver which makes it possible to detect phenomenon of pseudo hypertension was performed in 64 patients with elevated blood pressure when measured by Korotkoff's method. In 14 patients with essential hypertension and 14 patients with pseudo-hypertension the effect of 9 days hypotensive treatment with furosemide on renal function was compared. 22% of studied patients revealed pseudo-hypertension. The drop in arterial pressure caused a significant increase in the plasma urea, as well as a significant decrease in creatinine clearance and uric acid clearance in patients with pseudo-hypertension. These changes were not observed in patients with essential hypertension. Antihypertensive treatment of patients with pseudo-hypertension is hazardous due to the possibility of adverse effects caused by diminished tissue flow. Before starting the hypotensive therapy in elderly patients it is advisable to exclude pseudo-hypertension by means of Osler's maneuver. PMID- 1881833 TI - [Chlamydial infections in man]. PMID- 1881834 TI - [Endoscopic drainage of the bile ducts]. AB - Insertion of biliary endoprosthesis was attempted in 151 patients with obstructive jaundice and was successful in 124 patients (82%). The indications for the procedure were: 1) biliary and pancreatic neoplasms (79 patients) and 2) non-neoplastic diseases such as common bile duct stones or postoperative biliary strictures (45 patients). Successful drainage of bile was obtained in 95% of patients from the first group and in 93% of those from the second group. The mean survival time of patients with neoplasms was 4.5 months and the majority of them were free of jaundice and itching. In 32 patients with non-neoplastic diseases there was no recurrence of jaundice after a mean time of 20 months. Serious complications occurred in 5 patients (4%), 4 of them died (3.2%). The most frequent late complication was clogging of the endoprosthesis (19% of patients from the first group after a mean time of 5 months and in 28% of those from the second group after a mean time of 16 months). Replacement of the endoprosthesis was carried out mainly on the ambulatory basis. Endoscopic biliary stenting is an effective method of palliative biliary drainage in patients with non-operable biliary and pancreatic tumours. In high risk patients with non-neoplastic obstructive jaundice the technique may be an alternative for surgical treatment. PMID- 1881835 TI - Some conceptual problems in multivariable analyses of perinatal mortality. AB - Biostatisticians, epidemiologists and other researchers in maternal and child health have often used multivariable analysis to investigate associations with perinatal and infant mortality. A review of reports of such multivariable analyses published over the last 35 years revealed four problems that occur repeatedly. (1) Variables that are intermediate in the causal pathway between some study variables and perinatal death ('intervening variables') are controlled as though they were confounders. (2) When birthweight is analysed as an intervening variable, it is entered into the analysis in a few large categories, such as above and below 2500 g. This is not an adequate way of controlling for birthweight. (3) Social and demographic variables often interact statistically with birthweight in their effects on perinatal mortality, but these interactions have not been analysed in most multivariable studies. (4) Highly intercorrelated variables that represent similar theoretical constructs are entered simultaneously into one regression analysis. Solutions to these problems are suggested. Analytical approaches in which investigators use knowledge of biological and medical subject matter to make judgements about confounding and causal inference are encouraged. PMID- 1881836 TI - Fumes from the spleen. PMID- 1881837 TI - Differences in early postnatal morbidity risk by pattern of fetal growth in Argentina. AB - Information on a cohort of 5539 singleton births delivered at term in two hospitals in Rosario, Argentina, was used to examine differences in early postnatal morbidity between small for gestational age (SGA) infants classified by their ponderal index (PI). SGA infants with low PI (SGA-LPI) were 4.35 (90% CI: 1.50, 12.61) times more likely to have asphyxia, 13.75 (2.48, 76.31) times more likely to have hypoglycaemia and 2.32 (1.03, 5.26) times more likely to have respiratory distress (RD) than SGA infants with adequate PI (SGA-API). The increased risks of asphyxia and hypoglycaemia observed for SGA-LPI infants diminished, but remained statistically significant after controlling for the infant's gender, birthweight, gestational age and hospital of birth. There was no difference in risk of hyperbilirubinaemia between SGA-API and SGA-LPI infants. With the exception of risk of hyperbilirubinaemia, SGA-API infants carried the same risks of morbidity as non-SGA infants. The results of the study show that SGA infants do not constitute a homogeneous group with respect to their prospects for early postnatal health and survival. Furthermore, the pattern of differences in morbidity risk between SGA-API and SGA-LPI infants observed in this study is consistent with the timing hypothesis for the aetiology of variation in PI among SGA infants. PMID- 1881838 TI - Social differences in low birthweight and preterm deliveries in twins. AB - The relationship between low social class and low birthweight or preterm deliveries is well established in singletons but not in twins. We present a study using all twin deliveries registered in Belgium in 1983 and in Aberdeen between 1951 and 1983. No significant relationship was found between social class and low birthweight, very low birthweight or preterm deliveries in the Belgian sample. In Aberdeen, we found significantly higher rates of low birthweight twins in low social classes. This increase of low birthweight twins in low social classes occurred in Aberdeen during the period 1951-1968, but not in the more recent data. PMID- 1881839 TI - An educational intervention on promotion of breast feeding. AB - This study was designed to search for an effective method to promote exclusive breast feeding among Turkish city women delivering in hospitals. Four hundred and forty-two primiparae with uncomplicated deliveries and with healthy infants with birthweights of greater than 2500 g were exposed to a group educational session on breast feeding after birth, followed by one repeat session at home. Four hundred and ninety-nine women served as controls. All homes were visited monthly for 6 months by independent observers and data relevant to the feeding of the infants were collected. Weight measurements of 176 infants were taken at age 4 months. The study and control mothers were similar in sociodemographic characteristics which reflected a low socio-economic/educational background but relatively good housing conditions. Although significant differences in frequency of exclusive breast feeding were found between the study and control groups, the impact of the intervention was much lower than our expectations and short-lived. Type of feeding was not related to sex or birthweight of the infant, nor to maternal variables. Weight at age 4 months was within normal limits and similar in the study and control groups. It was concluded that lack of up-to-date information on infant feeding was the main obstacle to breast feeding in urban groups in Turkey, and that the impact of an educational intervention limited to the first week after delivery was lost within the first 2 months. PMID- 1881841 TI - Antenatal care received and its association with preterm birth in Greece. AB - A total population sample of singleton births to mothers with certain dates of last menstrual period (LMP) was identified from the Greek National Perinatal Survey of April 1983. Two groups of mothers were considered separately, 3116 primigravidae and 6524 multigravidae, with preterm birth rates of 5.9% and 8.4% respectively. Of all the antenatal care factors tested, primigravidae showed significant associations (unadjusted) with haematocrit level and with drugs taken during pregnancy. The logistic regression analysis which followed showed that the only factor independently associated with preterm delivery for that group of mothers was drugs taken during this period: women taking no drugs (including vitamins and iron) had the highest risk of preterm delivery. In contrast, multigravidae showed significant unadjusted associations with a great variety of parameters of antenatal care. Nevertheless, in the logistic regression analysis only three proved to have independent significant associations: drugs taken during pregnancy (reduced risk among mothers taking vitamins and iron), hospital admission during pregnancy (mainly for cervical cerclage) and the pattern of antenatal care during the first two trimesters (those attending the recommended number of times having least risk). PMID- 1881840 TI - An educational intervention on promotion of breast feeding complemented by continuing support. AB - The study, aiming to document the effect of continued support for mothers on frequency of exclusive breast feeding, was carried out by inclusion of breast feeding counselling in the context of well-baby care. One hundred and forty-six mothers who had been exposed to two educational sessions on breast feeding after delivery were given appointments to bring their baby to the paediatric hospital for well-baby care. The mother-infant pairs were followed by the same two residents for 4 months. Mean number of visits was six. A conscious effort was made during all visits to influence the mothers and their close relatives towards exclusive breast feeding. It was observed that in a large proportion of the infants, breast milk was being supplemented with water at the time of the first visit and no further effort was made to change this traditional behaviour. Comparison of the results with a group of mothers who had been exposed to similar educational sessions after delivery but without further support showed a striking increase in frequency of exclusive breast feeding (breast milk and water) in the supported group. PMID- 1881842 TI - Marijuana and spontaneous abortion of known karyotype. AB - We tested whether marijuana use in the 2 months before the last menstrual period and during pregnancy affects the risk of spontaneous abortions of known karyotype. Spontaneous abortions (cases) were defined as chromosomally normal (n = 567) or chromosomally aberrant (n = 393) and, within the latter, by type of aberration (212 trisomies, 71 monosomies X, 49 triploidies, 61 others). Controls were women with prenatal care before 22 weeks gestation and delivering at 28 weeks or later (n = 2042). In comparison with controls, adjusted odds (OR) of reported marijuana use in chromosomally normal cases were 1.1 (95% confidence interval (CI) 0.7, 1.5) and in chromosomally aberrant cases combined 1.2 (95% CI 0.7, 1.9). With respect to specific aberrations, use in the perifertilisation period did not differ significantly from that in controls for trisomies (adjusted OR = 0.8, 95% CI 0.4, 1.8), monosomies X (adjusted OR = 1.8, 95% CI 0.7, 4.3), and triploidies (adjusted OR = 1.3, 95% CI 0.4, 4.5). Comparison of karyotype groups with each other yielded similar results. Our data do not support causal associations of marijuana use, at the levels represented in our sample, with either chromosomally normal or trisomic spontaneous abortion. With monosomy X and triploidy, no statistically significant associations were detected although numbers were insufficient to rule out moderate effects. PMID- 1881843 TI - The Pregnancy Risk Assessment Monitoring System: design, questionnaire, data collection and response rates. PRAMS Working Group. AB - The birth certificate, the primary tool for population-based surveillance of the condition of infants at birth and maternal status during pregnancy, provides little data about maternal behaviour during pregnancy. To collect data on maternal behaviours that influence pregnancy outcome, we implemented the Pregnancy Risk Assessment Monitoring System in seven states. For this population based surveillance, new mothers were sampled from birth certificates 2 to 6 months after delivery and contacted by mail; follow-up of nonrespondents was by telephone. Participants completed a 10-page questionnaire. Stratification permitted over-sampling of women with adverse pregnancy outcomes. Among 10,563 women sampled during 1988 and 1989, stratum-specific response rates ranged from 30% to 89%. In 11 of the 28 strata, response rates were greater than 70%. Response rates varied considerably between states. Rates were lower for Black mothers, mothers of low birthweight infants, unmarried mothers and mothers with less than 12 years of education. Active refusal to participate and undelivered mail occurred infrequently. Mail and telephone surveillance of new mothers can yield adequate response rates in selected population groups. Trials of alternative approaches to enhancing response among Black and disadvantaged mothers, such as additional mailings or post-partum in-hospital recruitment, are needed. PMID- 1881844 TI - The Chiang Mai lactation project: study design and implementation. AB - The Chiang Mai lactation project is a longitudinal field study of human lactation carried out among northern Thai women living in the Sanpatong area of Chiang Mai Province. Its aim was to measure the volume and composition of breast milk transferred from mothers to their infants in the first year postpartum, and to relate it to predictors of milk production, and to the growth of the child. Breast milk and supplementary food intake, and nursing patterns, were recorded over two consecutive 24-hour periods six times during the first year. Samples of breast milk and of supplementary foods were analysed for energy and protein. Supplementary foods were also analysed for bacterial contamination. The growth of the child was measured, and health assessed using a combination of health diaries and examination by a physician. Recruitment to the study was excellent. After recruitment, two subjects left the study area, but otherwise only two dropped out, so complete sets of data covering these variables are available for 58 of the 62 recruited subjects. PMID- 1881845 TI - Myocardial rupture. Your patient's survival may depend on you. AB - Myocardial rupture is the second leading cause of in-hospital death from acute myocardial infarction. It is most likely to occur in the elderly, women, and patients with transmural infarction and no previous history of angina. A high index of suspicion is critical to the diagnosis. Myocardial rupture should be suspected when recurrent chest pain or hemodynamic instability develops after myocardial infarction. Rapid intervention and appropriate infarct-limiting therapy may reduce the mortality rate of this catastrophic complication. PMID- 1881846 TI - Preventive medicine in primary care. Moving from theory to practice. AB - Primary care physicians are in a unique position to offer preventive services. They have access to patients when intervention may be most successful, and they see most patients over a long period, which allows for adequate follow-up. The challenges are choosing the most effective interventions and organizing records and office staff to facilitate delivery of preventive services. Preventive medicine may not be as dramatic or as immediately successful as curative medicine, but it can have a tremendous long-term impact on health and well-being. PMID- 1881847 TI - How to recognize obsessive-compulsive disorder. AB - Your patient is anxious, depressed, and nervous, yet the complaint you are being asked to address is a respiratory infection. You suspect that the real problem may be obsessive-compulsive disorder. What should you do? How do you confidently and accurately reach the diagnosis? Dr Alarcon shares his expertise in recognition and management of this increasingly common disorder. PMID- 1881848 TI - How to diagnose bleeding disorders. AB - Patients with problems of hemostasis are not uncommon in the primary care setting. The bleeding history provides critical information that helps in guiding evaluation of these patients. Results of frequently used screening tests of coagulation can be abnormal in patients who have no significant hemostatic defect and can be normal in patients who do have one. PMID- 1881850 TI - Pseudomonas folliculitis from a health club whirlpool. AB - In public whirlpools, low disinfectant levels and inadequate monitoring are clearly a public health concern. Implementing guidelines published by the Centers for Disease Control seems to be the most reasonable approach to preventing dermatitis in persons who use these facilities. Physicians should be on the alert for well-demarcated rashes that may be associated with improperly maintained whirlpools. PMID- 1881849 TI - Choosing the right antibacterial agent. Is 'newer' always better? AB - The newer antibacterials are proving in some situations to be more effective than the older agents, and it is tempting to choose them. In many instances, however, traditional agents remain the treatment of choice. Major drawbacks of using newer antibacterials include their higher cost by weight, compared with older drugs, and the emergence of resistant organisms or superinfection as a result of overuse. The newer drugs are best reserved for use when older agents would be inadequate. PMID- 1881851 TI - Health insurance for all Americans? PMID- 1881852 TI - Carotid and coronary atherosclerosis. What are the connections? AB - In recent years research has revealed an association between carotid atherosclerosis and coronary atherosclerosis that parallels the long-recognized association between clinically manifest cerebrovascular disease and clinically manifest coronary artery disease (CAD). Validation of B-mode ultrasonography as a method for quantitative imaging of the extracranial carotid arteries has made it possible to identify risk factors for extracranial carotid atherosclerosis and its progression and to test pharmacologic agents for their ability to retard that progression. Extent of atherosclerosis in the extracranial carotid arteries has been shown to be a risk factor or "marker" for symptomatic CAD. In addition, CAD has been identified as an important predictor of progression of extracranial carotid atherosclerosis. PMID- 1881853 TI - Fecal occult blood testing. Guidelines for follow-up after positive findings. AB - Fecal occult blood testing should be performed under optimal conditions to minimize false-positive test results. Obvious bleeding from the rectum or other sources during the test period should be investigated and testing should be postponed. When a fecal occult blood test is positive, colonoscopy is recommended as the definitive method of diagnosis and often of treatment. When a complete colonoscopy cannot be performed, sigmoidoscopy with air-contrast barium enema is the next best alternative for direct visualization of the distal bowel and indirect investigation of the proximal colon. PMID- 1881854 TI - Hypertension in young patients. AB - Hypertension is often unrecognized in infants and children. Primary care physicians need the equipment necessary to measure blood pressure in young patients and tables or graphs showing normal values for age and sex. Children should have a blood pressure measurement and preventive counseling at each yearly checkup. Significant hypertension should never be dismissed as a temporary problem but rather should be carefully investigated, treated, and followed up. PMID- 1881856 TI - The patient factor. PMID- 1881855 TI - Septic shock. When patients fail to respond to conventional therapy. AB - Patients in septic shock require rapid evaluation and prompt initiation of therapy with appropriate antibiotics and fluids. When fluids do not restore perfusion, dopamine (Dopastat, Inotropin) therapy is begun. Some patients who fail to respond to these measures will respond to a combination of low-dose dopamine and regulation of blood pressure with norepinephrine (Levophed). PMID- 1881857 TI - Resource control versus healthcare rationing. PMID- 1881858 TI - Common triggers of asthma. AB - Control of asthma is enhanced when careful consideration is given to underlying mechanisms. Patients can be advised of ways to avoid or minimize contact with offending allergens, and, in some cases, pharmacologic management may not be necessary. Care must be taken when treating patients with concomitant disorders, such as hyperthyroidism. Also, psychological factors may have a role in exacerbating symptoms in suggestible patients. Noncompliance, in some cases due to inability to pay for medication, may be an unrecognized cause of treatment failure. PMID- 1881859 TI - Acute life-threatening asthma. AB - Although adrenergic therapy may be lifesaving in patients with severe acute asthma, attention must also be directed toward reversing underlying inflammation with corticosteroids. Other therapy for acute severe bronchospasm is controversial, although inhalant anticholinergic therapy may have adjunctive benefit. Aminophylline or magnesium sulfate may be indicated in those patients with life-threatening asthma who do not respond to conventional therapy. Chest radiographs are needed in patients who (1) present in extreme distress, (2) need to be hospitalized, or (3) have clinical manifestations of pneumonia or pneumothorax. Antibiotics are not used for acute asthma in the absence of pneumonia. PMID- 1881860 TI - New concepts in treatment of chronic persistent asthma. Using a stepwise protocol to control inflammation. AB - Asthma continues to cause unacceptably high rates of disability and death, largely because the severity of disease is underestimated and patients are inadequately educated about their disease. When patients understand what happens during an asthma attack and its aftermath, they are more likely to notice important symptoms and to start or increase self-treatment appropriately. Physicians are responsible for teaching patients how to avoid precipitating factors and for discussing and writing down a self-treatment plan to follow in specific circumstances. The British Thoracic Society has suggested a stepwise protocol for drug treatment of asthma. Each patient must be evaluated individually and started at the appropriate step. PMID- 1881861 TI - Rehabilitation of asthmatic patients. Motivating your patients to improve their life-style. AB - Complete rehabilitation of asthmatic patients requires consideration of their medication use, psychological adjustment, and quality of life and their family's adaptation to chronic disease. Physicians can significantly improve their patients' well-being by encouraging them to achieve and maintain a maximal level of fitness and to stop smoking. Motivation and support for smoking cessation should be available through office-based programs and follow-up. With pretreatment for vigorous sports, asthmatic patients should be able to participate in nearly any activity. PMID- 1881862 TI - Staving off acute otitis media. When is prophylaxis with antibiotics desirable? AB - Acute otitis media affects most young children and is the condition for which children are most frequently treated with antibiotics. A pattern of recurrent acute ear infections develops in some children and is a source of frustration for parents and physicians. Recurrent episodes can exacerbate asthma or other underlying medical problems, and long-term effects can include chronic otitis media with permanent middle-ear injury and, possibly, delay in psychomotor and language development. Antibiotic prophylaxis can reduce the number of episodes of acute otitis media in children at high risk for recurrent infection. There is no perfect antibiotic to prevent acute otitis media. However, the risks associated with the drugs described in this article are low. Prophylaxis with antibiotics does not prevent all episodes of acute otitis media but can reduce the number of episodes by 50%. PMID- 1881864 TI - Protein sequence comparison: methods and significance. PMID- 1881863 TI - Learning from the immune system: laboratory methods for creating and refining molecular diversity in polypeptides. PMID- 1881865 TI - Escherichia coli aspartate carbamoyltransferase: the probing of crystal structure analysis via site-specific mutagenesis. AB - Crystal structures are known for aspartate carbamoyltransferase (ATCase) in the T and R states, with and without the allosteric activator adenosine triphosphate (ATP) or inhibitor cytidine triphosphate (CTP). Visual inspection of X-ray crystal structures does not provide all of the information necessary for the determination of structure--function relationships in protein molecules. This problem is compounded because the crystalline states of the molecule may introduce effects due to crystal packing, restricted flexibility and less than optimum enzymatic conditions. Therefore, alternative techniques are required to test mechanisms conjectured from three-dimensional crystal structures of proteins. The technique of site-specific mutagenesis allows the researcher to test structure--function models based on three-dimensional structures and to obtain further insight into characteristics of the enzyme. Site-specific mutagenesis has been used to probe residues believed to be critical in the structure and function of ATCase. Selection of residues to be mutated has depended extensively on three-dimensional crystal structures of the enzyme. To date, 48 site-specific mutations at 37 different amino acid sites have been published. Although a total of 118 mutants at 58 different sites has been communicated to our laboratory, only published mutants will be considered in this review. In this paper, we compile for the first time, review, and analyze the site-specific mutants of ATCase. Site-specific mutagenesis of proteins has become a powerful technique in modern-day molecular biology, especially in studying a molecule as large as aspartate carbamoyltransferase. In this review, the role of site-specific mutagenesis of ATCase is discussed and improvements in the analysis are suggested. PMID- 1881866 TI - Reaction mechanism of trypsin-catalysed semisynthesis of human insulin studied by fast atom bombardment mass spectrometry. AB - The production of semisynthetic human insulin for therapeutic purposes is of considerable importance. During trypsin-catalysed transformation of pig insulin into an ester of insulin of human sequence, the alanyl residue at position B30 is removed and replaced with an esterified residue of threonine. We have carried out this transformation in a medium enriched in 18OH2 and studied the product by MS. In contrast to a previous report, we find that incorporation of label into the B29 - B30 peptide bond occurs during the transformation with threonine methyl ester in aqueous N,N-dimethylacetamide. Quantitative data are presented and the implications of these findings are discussed. PMID- 1881867 TI - Similarity graphing and enzyme-reaction database: methods to detect sequence regions of importance for recognition of chemical structures. AB - We developed a new method which searches sequence segments responsible for the recognition of a given chemical structure. These segments are detected as those locally conserved among a sequence to be analyzed (target sequence) and a set of sequences (reference sequences). Reference sequences are the sequences of functionally related proteins, ligands of which contain a common chemical substructure in their molecular structures. 'Similarity graphing' cuts target sequences into segments, aligns them with reference sequence pairwise, calculates the degree of similarity for each alignment, and shows graphically cumulative similarity values on target sequence. Any locally conserved regions, short or long in length and weak or strong in similarity, are detected at their optimal conditions by adjusting three parameters. The 'enzyme-reaction database' contains chemical structures and their related enzymes. When a chemical substructure is input into the database, sequences of the enzymes related to the input substructure are systematically searched from the NBRF sequence database and output as reference sequences. Examples of analysis using similarity graphing in combination with the enzyme-reaction database showed a great potentiality in the systematic analysis of the relationships between sequences and molecular recognitions for protein engineering. PMID- 1881868 TI - Graphical representation of hydrogen bonding patterns in proteins. AB - A graphical representation of the intramolecular hydrogen bonding in a protein is described, which provides a direct and easily interpretable display of its secondary and tertiary structural elements. The representation is constructed by scanning the coordinate list for all potential proton donor (PD)--proton acceptor (PA) pairs, and any pair which satisfies certain preset distance and angle criteria is classified as being H-bonded. The resulting list of H-bonds is mapped onto an N x N matrix, where N is the number of residues in the protein, by assigning an element ij of the matrix to all the PA-PD pairs between atoms of residues i and j. Subsequently graphical objects are generated for all elements which are labeled as representing one or more H-bonds, and which can then be plotted or displayed in a way analogous to the graphical representation of the distance matrix (DM). In contrast to the DM, the hydrogen bonding matrix (HBM) is sparse, which allows the patterns representing secondary and tertiary structural motifs to be quickly and clearly recognized. In addition, changes in structure are easily identifiable from changes in the H-bonding patterns. The analysis and interpretation of the HBM is discussed using aspartate amino-transferase and calmodulin as examples. PMID- 1881869 TI - Adaptability of restrained molecular dynamics for tertiary structure prediction: application to Crotalus atrox venom phospholipase A2. AB - In order to assess the adaptability and/or applicability of the restrained molecular dynamics (RMD) simulation for building a possible tertiary structure of a protein from the X-ray crystal structure of a family reference protein, the tertiary structure prediction of Crotalus atrox venom phospholipase A2 (PLA2) was attempted based on the X-ray crystal structure of bovine pancreatic PLA2. For the formation of secondary and tertiary structures from the fully extended starting structure, the RMD simulation with interatomic distance restraints and torsion angle restraints, which were derived from homologous amino acid sequence regions in the reference protein, was carried out until the molecular system was fully equilibrated. The predicted tertiary structure of C. atrox venom PLA2 was compared with its X-ray crystal structure, and furthermore the utility of this method was discussed by reference to the similar tertiary structure prediction of beta-trypsin from the X-ray crystal structure of an elastase. PMID- 1881870 TI - Confirmation of the predicted source of a slow folding reaction: proline 8 of bovine pancreatic trypsin inhibitor. AB - A major question in protein structural analysis concerns the applicability of results from model systems to other proteins. Theoretical approaches seem the best manner of transferring information from one system to another, but their accuracy in the model systems must first be tested with results from experiment. Since bovine pancreatic trypsin inhibitor (BPTI) is a model system for the evaluation of energy minimization and molecular dynamics routines, we can use folding and stability measurements to examine the reliability of these methods. All two-disulfide mutants of BPTI investigated thus far have two very slow folding reactions which have characteristics of proline isomerization. These reactions may occur because the non-native cis form of two of the four prolines in BPTI significantly destabilizes the folded state of the protein. Previous energy minimization studies of wild-type BPTI suggested that the cis form of Pro8 was the most destabilizing of the four prolines [Levitt,M. (1981) J. Mol. Biol., 145, 251-263]. In this paper, we show that mutation of Pro8----Gln in the two disulfide bond mutant Val30/Ala51 results in a loss of the slowest folding reaction, consistent with Levitt's prediction. PMID- 1881871 TI - Engineering the quaternary structure of an exported protein with a leucine zipper. AB - The leucine zipper of the yeast transcriptional factor GCN4 was grafted to the C terminal amino acid of the maltose binding protein (MalE) by fusing the malE gene of Escherichia coli to a synthetic gene coding for the leucine zipper. The hybrid protein, MalE-Lzp, was synthesized in large amounts from multicopy plasmids and efficiently exported into the periplasmic space of E. coli, up to 200,000 molecules per cell. Unlike hybrids between MalE and other proteins, MalE-Lzp was quite stable exhibiting only minimal degradation. The hybrid was purified from a periplasmic extract in one step by affinity chromatography on cross-linked amylose. Sedimentation velocity and gel filtration experiments showed that MalE Lzp existed as a dimer in conditions where MalE was a monomer, at all concentrations tested down to 0.1 microM. Thus, it was possible to engineer the quaternary structure of an exported, monomeric protein by using a structural motif taken from a natural protein. PMID- 1881872 TI - Protein engineering of diphtheria-toxin-related interleukin-2 fusion toxins to increase cytotoxic potency for high-affinity IL-2-receptor-bearing target cells. AB - We have used site-directed insertion and point mutagenesis in an attempt to increase the cytotoxic potency and receptor-binding affinity of the diphtheria toxin-related interleukin-2 (IL-2) fusion toxins. Previous studies have demonstrated that both the DAB486-IL-2 and DAB389-IL-2 forms of the fusion toxin consist of three functional domains: the N-terminal fragment-A-associated ADP ribosyltransferase, the hydrophobic-membrane-associating domains, and the C terminal receptor-binding domain of human IL-2. By insertion mutagenesis we have increased the apparent flexibility of the polypeptide chain between the membrane associating domains and the receptor-binding domain of this fusion toxin. In comparison to DAB486-IL-2, the cytotoxic potency of the insertion mutants was increased by approximately 17-fold for high-affinity IL-2-receptor-bearing cell lines in vitro. Moreover, competitive displacement experiments using [125I]rIL-2 demonstrate that the increase in cytotoxic potency correlates with an increase in receptor-binding affinity for both the high and intermediate forms of the IL-2 receptor. PMID- 1881873 TI - Enzyme IIIlac of the staphylococcal phosphoenolpyruvate-dependent phosphotransferase system: site-specific mutagenesis of histidine residues, biochemical characterization and 1H-NMR studies. AB - The lactose-specific phosphocarrier protein enzyme III of the bacterial phosphoenol-pyruvate-dependent phosphotransferase system of Staphylococcus aureus was modified by site-specific mutagenesis on the corresponding lacF gene in order to replace the histidine residues 78 and 82 of the amino acid sequence with a serine residue. Wild-type and both mutant genes were overexpressed in Escherichia coli and the gene products were purified to homogeneity. The conformation of wild type and mutant proteins were monitored by 1H-NMR spectroscopy. In vitro phosphorylation studies on mutant lactose-specific enzyme III, as well as evidence from NMR spectroscopy, lead to the conclusion that His78 is the active site for phosphorylation of lactose-specific enzyme III by phospho-HPr (histidine containing protein). The role of His82 probably is the enhancement of velocity and efficiency of the phosphotransfer from lactose-specific enzyme III to lactose specific enzyme II. This result refutes the conclusion of former work based on data by protelytic cleavage and sequencing of the 32P-labeled peptide of lactose specific enzyme III that His82 is the active-site for phosphorylation. PMID- 1881874 TI - Staphylococcal lactose phosphoenolpyruvate-dependent phosphotransferase system: site-specific mutagenesis on the lacE gene gives evidence that a cysteine residue is responsible for phosphorylation. AB - The lactose-specific phosphocarrier protein enzyme II of the bacterial phosphoenol-pyruvate-dependent phosphotransferase system of Staphylococcus aureus was modified by site-specific mutagenesis on the corresponding lacE gene in order to replace the histidine residues 245, 274 and 510 and the cysteine residue 476 of the amino acid sequence with a serine residue. The wild-type and mutant genes were expressed in Escherichia coli and the gene products were characterized in different in vitro test systems. In vitro phosphorylation studies on mutant derivatives of the lactose-specific enzyme II led to the conclusion that cysteine residue 476 is the active-site for phosphorylation of this enzyme II by a phospho enzyme III of the same sugar specificity. A cysteine residue phosphorylated intermediate was first postulated for the mannitol-specific enzyme II of E. coli and studies performed independently concerning the lactose-specific enzyme II of Lactobacillus casei are in agreement with the above results. PMID- 1881876 TI - Expression of active domains of a human folate-dependent trifunctional enzyme in Escherichia coli. AB - The cDNA encoding the human trifunctional enzyme methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase was engineered to contain a prokaryotic ribosome binding site and was expressed under the bacteriophage T7 RNA polymerase promoter in Escherichia coli. Site-directed mutagenesis was used to prepare constructs that encode separately the dehydrogenase/cyclohydrolase (D/C) domain as amino acid residues 1-301, and the synthetase (Syn) domain as residues 304-935. Both domains formed active enzymes thereby demonstrating their ability to fold independently. The full length enzyme, D/C and Syn domains were expressed at levels 4-, 55- and 3-fold higher than the specific activities found in liver. Additional mutagenesis and independent expression of domains further defined the interdomain region to include amino acids 292-310. The D/C domain was purified to homogeneity by a single affinity chromatographic step, and the full-length protein in a two-step procedure. The kinetic properties of the D/C domain appear unaltered from those of the trifunctional enzyme. PMID- 1881875 TI - Engineering of the Lactococcus lactis serine proteinase by construction of hybrid enzymes. AB - Plasmids containing wild-type and hybrid proteinase genes were constructed from DNA fragments of the prtP genes of Lactococcus lactis strains Wg2 and SK11. These plasmids were introduced into the plasmid-free strain L. lactis MG1363. The serine proteinases produced by these L. lactis strains were isolated, and their cleavage specificity and rate towards alpha s1- and beta-casein was investigated. The catalytic properties of both the SK11 and Wg2 proteinases, which differ in 44 out of 1902 amino acid residues, could be changed dramatically by the reciprocal exchange of specific fragments between the two enzymes. As a result, various L. lactis strains were constructed having new proteolytic properties that differ from those of the parental strains. Furthermore, two segments in the proteinase could be identified that contribute significantly to the cleavage specificity towards casein; within these two segments, several amino acid residues were identified that are important for substrate cleavage rate and specificity. The results also indicate that the lactococcal proteinase has an additional domain involved in substrate binding compared with the related subtilisins. This suggests that the 200 kd L. lactis proteinase may be the representative of a new subclass of subtilisin-like enzymes. PMID- 1881877 TI - 1.59 A structure of trypsin at 120 K: comparison of low temperature and room temperature structures. AB - The structure of a rat trypsin mutant [S195C] at a temperature of 120 K has been refined to a crystallographic R factor of 17.4% between 12.0 and 1.59 A and is compared with the structure of the D102N mutant at 295 K. A reduction in the unit cell dimensions in going from room temperature to low temperature is accompanied by a decrease in molecular surface area and radius of gyration. The overall structure remains similar to that at room temperature. The attainable resolution appears to be improved due to the decrease in the fall off of intensities with resolution [reduction of the temperature factor]. This decreases the uncertainty in the atomic positions and allows the localization of more protein atoms and solvent molecules in the low temperature map. The largest differences between the two models occur at residues with higher than average temperature factors. Several features can be localized in the solvent region of the 120 K map that are not seen in the 295 K map. These include several more water molecules as well as an interstitial sulfate ion and two interstitial benzamidine molecules. PMID- 1881878 TI - Proline in alpha-helix: stability and conformation studied by dynamics simulation. AB - Free-energy simulations have been used to estimate the change in the conformational stability of short polyalanine alpha-helices when one of the alanines is replaced by a proline residue. For substituting proline in the middle of the helix the change in free energy of folding (delta delta G degrees) was calculated as 14 kJ/mol (3.4 kcal/mol), in excellent agreement with the one available experimental value. The helix containing proline was found to be strongly kinked; the free energy for reducing the angle of the kink from 40 degrees to 15 degrees was calculated, and found to be small. A tendency to alternate hydrogen bonding schemes was observed in the proline-containing helix. These observations for the oligopeptide agree well with the observation of a range of kink angles (18-35 degrees) and variety of hydrogen bonding schemes, in the rare instances where proline occurs in helices in globular proteins. For substituting proline at the N-terminus of the helix the change in free energy of folding (delta delta G degrees) was calculated as -4 kJ/mol in the first helical position (N1) and +6 kJ/mol in the second helical position (N2). The observed frequent occurrence of proline in position N1 in alpha-helices in proteins therefore has its origin in stability differences of secondary structure. The conclusion reached here that proline may be a better helix former in position N1 than (even) alanine, and thus be a helix initiator may be testable experimentally by measurements of fraction helical conformation of individual residues in oligopeptides of appropriate sequence. The relevance of these results in regards to the frequent occurrence of proline-containing helices in certain membrane proteins is discussed. PMID- 1881879 TI - Secondary structure-based profiles: use of structure-conserving scoring tables in searching protein sequence databases for structural similarities. AB - The profile method, for detecting distantly related proteins by sequence comparison, has been extended to incorporate secondary structure information from known X-ray structures. The sequence of a known structure is aligned to sequences of other members of a given folding class. From the known structure, the secondary structure (alpha-helix, beta-strand or "other") is assigned to each position of the aligned sequences. As in the standard profile method, a position dependent scoring table, termed a profile, is calculated from the aligned sequences. However, rather than using the standard Dayhoff mutation table in calculating the profile, we use distinct amino acid mutation tables for residues in alpha-helices, beta-strands or other secondary structures to calculate the profile. In addition, we also distinguish between internal and external residues. With this new secondary structure-based profile method, we created a profile for eight-stranded, antiparallel beta barrels of the insecticyanin folding class. It is based on the sequences of retinol-binding protein, insecticyanin and beta lactoglobulin. Scanning the sequence database with this profile, it was possible to detect the sequence of avidin. The structure of streptavidin is known, and it appears to be distantly related to the antiparallel beta barrels. Also detected is the sequence of complement component C8, which we therefore predict to be a member of this folding class. PMID- 1881880 TI - Crystallographic refinement of ricin to 2.5 A. AB - The plant cytotoxin ricin consists of two disulfide-linked chains, each of about 30,000 daltons. An initial model based on a 2.8 A MIR electron density map has been refined against 2.5 A data using rounds of hand rebuilding coupled with either a restrained least squares algorithm or molecular dynamics (XPLOR). The last model (9) has an R factor of 21.6% and RMS deviations from standard bond lengths and angles of 0.021 A and 4.67 degrees, respectively. Refinement required several peptide segments in the original model to be adjusted translationally along the electron density. A wide range of lesser changes were also made. The RMS deviation of backbone atoms between the original and model 9 was 1.89 A. Molecular dynamics proved to be a very powerful refinement tool. However, tests showed that it could not replace human intervention in making adjustments such as local translations of the peptide chain. The R factor is not a completely satisfactory indicator of refinement progress; difference Fouriers, when observed carefully, may be a better monitor. PMID- 1881881 TI - Structure of ricin A-chain at 2.5 A. AB - Ricin has been refined in a crystallographic sense to 2.5 A resolution and the model for the A-chain (RTA) is described in detail. Because RTA is the first member of the class of plant toxins to be analyzed, this model probably defines the major structural characteristics of the entire family of these medically important proteins. Explanations are provided to rationalize amino acids that are conserved between RTA and a number of homologous plant and bacterial toxins. Eight invariant residues appear to be involved in creating or stabilizing the active site. In the active site Arg180 and Glu177 are hydrogen bonded to each other and also coordinate a water molecule; each of these groups may be important in the N-glycosidation reaction. Several other polar residues may play lesser roles in the mechanism, including tyrosines 80 and 123 and asparagines 78 and 209. A number of conserved hydrophobic residues are seen to cluster within several patches and probably drive the overall folding of the toxin molecule. PMID- 1881882 TI - Structure of ricin B-chain at 2.5 A resolution. AB - The heterodimeric plant toxin ricin has been refined to 2.5 A resolution. The B chain lectin (RTB) is described in detail. The protein has two major domains, each of which has a galactose binding site. RTB has no regular secondary structure but displays several omega loops. Each RTB domain is made of three copies of a primitive 40 residue folding unit, which pack around a pseudo threefold axis. In each domain, galactose binds in a shallow cleft formed by a three residue peptide kink on the bottom and an aromatic ring on the top. At the back of the cleft, an aspartate forms hydrogen bonds to the C3 and C4 hydroxyls of galactose, whereas a glutamine bonds to the C4 alcohol, helping to define specific epimer binding. In addition to analyzing the sugar binding mechanism, the assembly of subdomain units around the pseudo threefold axis of each domain is described. The subdomains contribute conserved Trp, Leu, and Ile residues to a compact central hydrophobic core. This tight threefold binding probably drives the peptide folding and stabilizes the protein structure. PMID- 1881883 TI - Site-directed mutagenesis of ricin A-chain and implications for the mechanism of action. AB - Ricin A-chain is an N-glycosidase that attacks ribosomal RNA at a highly conserved adenine residue. The enzyme is representative of a large family of medically significant proteins used in the design of anticancer agents and in the treatment of HIV infection. The x-ray structure has been used as a guide to create several active site mutations by directed mutagenesis of the cloned gene. Glu177 is a key catalytic residue, and conversion to Gln reduces activity 180 fold. Asn209 is shown to participate in substrate binding by kinetic analysis. Conversion to Ser increases Km sixfold but has no effect on kcat. Conversion of Tyr80 and Tyr123 to Phe decreases activity by 15- and 7-fold respectively. A mechanism of action is proposed that involves binding of the substrate adenine in a syn configuration that resembles the transition state; the putative oxycarbonium ion is probably stabilized by interaction with Glu177. PMID- 1881884 TI - The carbohydrate domain of calicheamicin gamma I1 determines its sequence specificity for DNA cleavage. AB - We have investigated the DNA cleaving properties of calicheamicinone, the synthetic core aglycone of calicheamicin gamma I1, a natural product with extremely potent antitumor activity. Our experiments have shown that the synthetic analog binds and cleaves DNA, albeit without any sequence selectivity and with less efficiency than the natural compound. We propose that a key element in the sequence recognition process is the thiobenzoate ring present in the natural compound. We have demonstrated by one-dimensional NMR that there is direct hydrogen abstraction from DNA by calicheamicinone, with enhanced binding affinity contributed by the carbohydrate domain. The reduced efficiency of hydrogen abstraction from DNA by bound calicheamicinone, compared with the natural compound, implicates the carbohydrate moiety in positioning the drug for hydrogen abstraction. PMID- 1881886 TI - Parameters of the human genome. AB - Chromosome arm lengths are the critical parameters of the human genome. The physical length is required to scale radiation hybrid and other maps to megabases. The genetic lengths in males and females are required for probabilities of exclusion and synteny, choice of well-spaced loci for linkage tests, and comparison with centromeric maps based on nondisjunction. Interpolation of new data into a map is possible only when the length is known, including the distances from centromere and telomeres to the nearest markers. Current evidence on physical parameters including the reliable measurements of relative lengths from flow cytometry but only a crude estimate of genome size (3200 megabases). Evidence on genetic parameters includes chiasma counts and linkage maps corrected for failure to sample telomeres, giving an autosomal size of 2809 centimorgans in males and 4782 centimorgans in females. Estimates of the physical and sex-specific genetic lengths are presented for each chromosome arm. Any linkage analysis that yields substantially larger estimates raises a suspicion of an inappropriate mapping function or typing errors. PMID- 1881885 TI - Localization of heterogeneous nuclear ribonucleoprotein in the interphase nuclear matrix core filaments and on perichromosomal filaments at mitosis. AB - Although heterogeneous nuclear RNA (hnRNA) has been localized to the core filament substructure of the nuclear matrix, its precise location in the filament network has been unknown. The fA12 monoclonal antibody can localize, at high resolution, hn ribonucleoproteins (hnRNPs) and, presumably, hnRNA. Gold bead immunolabeling of resinless electron microscopy sections showed the fA12 antigens were in the fibrogranular material enmeshed in the filament network and not in the filaments themselves. At mitosis, hnRNP antigens became dispersed into a halo surrounding the chromosomes and spindle poles. Immunogold staining showed fA12 stained fibrogranular material associated with perichromosomal and pericentriolar filaments distinct from the mitotic spindle fibers. fA12 also labeled the midbody remaining after cytokinesis. PMID- 1881887 TI - Radiation hybrid mapping. AB - A theory is developed to predict marker retention and conditional retention or loss in radiation hybrids. Applied to multiple pairwise analysis of a human chromosome 21 data set, this theory fits much better than proposed alternatives and gives a physical map consistent with other evidence and robust with respect to errors to typing. Radiation hybrids have great promise to provide order and physical location at two levels of resolution, spanning the techniques of linkage and restriction fragments and not limited to polymorphic loci. PMID- 1881888 TI - Differential tissue localization of oviduct and erythroid transferrin receptors. AB - The tissue distributions of the estrogen-inducible hen oviduct transferrin receptor and the chicken embryonic erythrocyte transferrin receptor were studied. Tissue sections were investigated by immunofluorescence microscopy using specific polyclonal antisera against each receptor. The receptor originally identified and characterized in the oviduct strongly stained liver and ovary; localized staining was observed in the brain (especially endothelial cells). Staining of breast muscle and heart tissue occurred only in occasional interstitial cells. Antiserum against oviduct transferrin receptor did not stain erythrocytes, either from embryos or from mature animals. On the other hand, the antiserum directed against the embryonic erythrocyte receptor stained embryonic erythrocytes; it did not stain any other tissues. The fluorescence microscopy observations were confirmed by Western blot analysis. The strong staining of oviduct, liver, and ovary suggests a major role for the oviduct transferrin receptor in oogenesis. PMID- 1881890 TI - Long-term reconstitution of the mouse hematopoietic system by embryonic stem cell derived fetal liver. AB - Murine embryonic stem (ES) cells are permanent blastocyst-derived cell lines capable of contributing to a wide variety of tissues, including the germ line, after injection into host blastocysts. Recently, we have shown that ES cells can produce all of the cells of the developing fetus after aggregation with developmentally compromised tetraploid embryos. Completely ES cell-derived embryos die perinatally, but the liver of these embryos is a source of entirely ES cell-derived hematopoietic progenitors. We have taken 14- to 15-day fetal liver cells from ES cell-tetraploid chimeras and reconstituted the hematopoietic system of lethally irradiated adult recipient mice. ES cell-derived hematopoietic stem cells were capable of long-term (greater than 6 months) repopulation of irradiated recipients, and all hematopoietic cell lineages analyzed (erythrocytes, T cells, mast cells, and macrophages) were derived exclusively from ES cells in such recipients. Thus, ES cells retain the capacity to differentiate into all hematopoietic cell types after prolonged passage in culture. This approach should provide a direct route to the production of mice whose hematopoietic cells carry genetic alterations that would be lethal if passed through the germ line. PMID- 1881889 TI - RNA polymerase II-associated proteins are required for a DNA conformation change in the transcription initiation complex. AB - Proteins purified on the basis of their affinity for RNA polymerase II effectively substitute for previously defined transcription initiation factors. In two assays, formation of initiation complexes and transcription in vitro, the RNA polymerase II-associated proteins behaved identically to a fraction containing transcription factors IIE and IIF. Both fractions greatly stabilized the association of polymerase with the promoter and were required for the formation of complete initiation complexes. By using the DNA-cleaving reagent phenanthroline.copper in footprinting reactions, the RNA polymerase II-associated proteins were shown to be required for a DNA conformation change near the initiation site of the promoter. Based on similarity to the prokaryotic transcription complex, this conformation change is likely to represent a transition from a closed to an open complex. PMID- 1881891 TI - Dominant expression of a distinctive V14+ T-cell antigen receptor alpha chain in mice. AB - A distinctive variable region 14-positive (V14+) alpha chain (V alpha 14+) of the T-cell antigen receptor is predominantly expressed in multiple mouse subspecies. The V alpha 14 family has two members, V alpha 14.1 and V alpha 14.2, which differ by only three amino acids at positions 50-52. Based on the EcoRI restriction fragment length polymorphism of the gene encoding V alpha 14, mice can be divided into three groups: type I with an 11.2-kilobase (kb) fragment, type II with a 2.0-kb fragment, and type III with the 2.0-kb and 11.2-kb fragments. Usage of V alpha 14-J alpha 281, where J alpha 281 is an alpha-chain joining segment, with a one-base N region dominates at the level of 0.02-1.5% of alpha chains in all laboratory strains, Mus musculus castaneus, and Mus musculus domesticus but not in Mus musculus molossinus, Mus musculus musculus, and Mus spicilegus samples. The preferential V alpha 14-J alpha 281 expression seems to be due to positive selection because the V-J junctional region is always glycine, despite the ability of the V alpha 14 gene to associate with J alpha other than J alpha 281. As V alpha 14-J alpha 281 expression is independent of known major histocompatibility complex antigens, including H-2, TLA, Qa, and HMT, the selecting ligand must be a monomorphic molecule of the mouse, expressed in a subspecies-specific manner. Additional observations, such as the expression of homogeneous V alpha 14-J alpha 281 in athymic mice, suggest that the positive selection of V alpha 14+ T cells occurs extrathymically. PMID- 1881892 TI - Functional significance of an overlapping consensus binding motif for Sp1 and Zif268 in the murine adenosine deaminase gene promoter. AB - The murine adenosine deaminase (ADA) gene has a (G + C)-rich promoter that can support diverse tissue-specific gene expression. By using deletion and mutation analyses, we have identified a cis-acting "repressor" element located immediately upstream of the proximal Sp1 binding site in the ADA gene promoter. This repressor element was localized to a binding site for the immediate-early, serum responsive, DNA binding factor Zif268. This Zif268 binding site partially overlaps a binding site for the general transcription activator Sp1. Disruption of the Zif268 binding site without disturbing the Sp1 binding motif abolished Zif268 binding and resulted in significantly elevated promoter function. Conversely, disruption of the proximal consensus Sp1 binding motif without disturbing the Zif268 binding site resulted in a loss of Sp1 binding at that region and greatly reduced promoter activity. Our results suggest that one function of Zif268 may be to down-regulate this type of mammalian gene promoter by competing with Sp1 for binding to the overlapping binding motif. PMID- 1881893 TI - Deletional switch recombination occurs in interleukin-4-induced isotype switching to IgE expression by human B cells. AB - There is controversy as to whether deletional rearrangement occurs between the IgM and IgE switch regions (S mu and S epsilon, respectively) during switching to the IgE isotype. We have addressed the issue by stimulating normal human B cells, sorted for lack of expression of surface IgE, to produce IgE by infection with Epstein-Barr virus (EBV) in the presence of interleukin 4 (IL-4). Genomic DNA was amplified for S mu/S epsilon switch junction fragments by utilizing the nested primer polymerase chain reaction. Switch junction fragments were amplified from B cells infected with EBV in the presence of IL-4 but not from B cells infected with EBV alone. The DNA sequence of these "switch fragments" revealed direct joining of S mu to S epsilon in each case. The recombination sites within S mu were clustered within 900 base pairs at the 5' end of the switch region, suggesting that there are "hot spots" for recombination within S mu. The S epsilon recombination sites were scattered throughout the S epsilon region. These findings indicate that IL-4-induced isotype switching to IgE production in human B cells is accompanied by DNA rearrangements with joining of S mu to S epsilon. PMID- 1881895 TI - Analyses of T-cell differentiation from hemopoietic stem cells in the G0 phase by an in vitro method. AB - Using differential radiation sensitivity of components of mouse embryonal thymus, an in vitro method for studying T-cell differentiation from hemopoietic stem cells (HSCs) in the G0 phase was established. Intrathymic T-cell precursors present in embryonal thymus were found to be quite radioresistant (up to 20 Gy), and consequently 25-Gy-irradiated embryonal thymic lobes were used. Thymic lobes (25-Gy irradiated) taken from mouse fetuses (gestation day 15) were placed in Millipore-HA culture plates supported on squares of gelatin foam sponge in 24 well culture plates in which neonatal thymus stromal cells were cultured. HSCs (10(5) cells per well) in the G0 phase were added to these thymic lobes and cocultured at 37 degrees C in a 5% CO2/95% air incubator. Half the culture medium was changed every week. After 3 weeks, a large number of colonies had formed. Immunohistochemical studies and fluorescence-activated cell sorter analyses revealed that the colonizing cells regularly develop and exhibit surface markers characteristic of T cells (Thy-1, IL-2R, L3T4, Lyt-2, etc.). In situ hybridization analyses revealed that mRNA expression for T-cell receptor (TCR) beta chains occurred within colonizing cells. Using a monoclonal antibody (F23.1), expression of TCR beta-chain variable domain (V beta 8) on the surface of these developing T cells was demonstrated. These cells responded to interleukin 2 and/or anti-CD3 monoclonal antibody, indicating functional T cells. This method will be useful in studying T-cell differentiation pathways from pluripotent HSCs and in clarifying the mechanisms involved in negative and positive selection of T cells within the thymus. PMID- 1881894 TI - Staphylococcal exotoxins deliver activation signals to human T-cell clones via major histocompatibility complex class II molecules. AB - We investigated whether staphylococcal exotoxins (SEs), in addition to their capacity to induce T-cell activation restricted by the T-cell receptor (TCR) beta chain variable region, can deliver an activation signal to human T-cell clones through major histocompatibility complex (MHC) class II molecules. Eleven human T cell clones (9 alpha beta TCR and 2 gamma delta TCR clones) of different antigenic specificities were tested for their capacity to proliferate in response to toxic shock syndrome toxin 1 (TSST-1) and two SEs, SEA and SEB. In the absence of accessory cells, only 4 alpha beta TCR clones were stimulated to proliferate, each by a single SE, and to mobilize intracellular free Ca2+ in response to that SE, events indicative of TCR engagement and, presumably, recognition restricted by the beta-chain variable region. In the presence of accessory cells, each of the 11 T-cell clones was stimulated to proliferate by any one of the three SEs tested. This apparently TCR-unrestricted SE-mediated polyclonal proliferation of T-cell clones occurred in the absence of an increase in intracellular free Ca2+ and was not dependent on the presence of MHC class II expression on accessory cells. In contrast, SE-mediated polyclonal proliferation did not occur in 3 alpha beta TCR clones derived from an MHC class II-deficient patient. Furthermore, all of the three SEs induced the proliferation of 4 natural-killer-cell clones, suggesting that expression of TCR/CD3 complex is not essential for SE-mediated polyclonal proliferation of activated lymphocytes. These results indicate that MHC class II molecules transduce activation signals to human T- and natural killer-cell clones. PMID- 1881897 TI - Stimulus selectivity and state dependence of activity in inferior temporal cortex of infant monkeys. AB - Inferior temporal cortex is necessary for visual object recognition in adult primates but is less critical in infants. Nonetheless, in macaques as young as 6 weeks old, inferior temporal neurons showed adult-like visual response properties, including form selectivity and bilateral receptive fields, indicating that extended maturation and visual experience may not be necessary for adult like encoding of complex objects. However, before the animals were 4 months old, visual responsiveness was found in inferior temporal cortex only in awake monkeys performing a behavioral task and not in anesthetized ones, suggesting that extraretinal factors profoundly influence function in "association" cortex in developing as well as mature animals. PMID- 1881896 TI - Angiotensin II receptor subtypes are coupled with distinct signal-transduction mechanisms in neurons and astrocytes from rat brain. AB - Both neurons and astrocytes contain specific receptors for angiotensin II (AII). We used selective ligands for the AT1 and AT2 types of AII receptors to investigate the expression of functional receptor subtypes in astrocyte cultures and neuron cultures from 1-day-old (neonatal) rat brain. In astrocyte cultures, competition of 125I-labeled AII (125I-AII) specific binding with AT1 (DuP753) or AT2 (PD123177, CGP42112A, [Phe(p-NH2)6]AII) selective receptor ligands revealed a potency series of AII greater than DuP753 much greater than CGP42112A greater than [Phe(p-NH2)6]AII greater than PD123177. These results suggest a predominance of the AT1 receptor subtype in neonatal astrocytes. Also, in astrocyte cultures, AII stimulated increases in inositolphospholipid hydrolysis that were significantly reduced by the AT1 receptor antagonist DuP753 but not altered by the AT2 receptor antagonist PD123177. In neonatal neuron cultures, competition of 125I-AII specific binding with the above ligands revealed a potency series of CGP42112A = AII greater than [Phe(p- NH2)6]AII greater than PD123177 much greater than DuP753. 125I-AII specific binding to neonate neuronal cultures was reduced 73-84% by 1 microM PD123177, and the residual 125I-AII specific binding was eliminated by DuP753. Also, in neuron cultures, AII induced decreases in basal cGMP that were completely blocked by PD123177 or CGP42112A but not by DuP753. Our results suggest that astrocyte cultures from neonatal rat brains contain predominantly AT1 receptors that are coupled to a stimulation of inositophospholipid hydrolysis. In contrast, neuron cultures from neonatal rat brain contain mostly AT2 receptors that are coupled to a reduction in basal cGMP levels, but a smaller population of AT1 receptors is also present in these neurons. PMID- 1881898 TI - Mediation of the short-loop negative feedback of luteinizing hormone (LH) on LH releasing hormone release by melatonin-induced inhibition of LH release from the pars tuberalis. AB - The pineal hormone melatonin is thought to mediate the effects of the pineal gland on seasonal reproduction by altering the release of gonadotropins. The mechanism by which melatonin controls gonadotropin secretion has been obscure. Recently, labeled 2-iodomelatonin was used to localize melatonin receptors in brain by radioautography. The highest concentration of melatonin receptors was found in the pars tuberalis of the pituitary gland of mammals. Pituitary hormones, in particular luteinizing hormone (LH), have been localized in cells of the pars tuberalis. Consequently, we hypothesized that melatonin might act on its receptors in the pars tuberalis to alter the release of LH. It would then be possible for this LH to diffuse into the overlying median eminence, there to alter the release of LH-releasing hormone (LHRH) from the axons of the LHRH neurons. To evaluate this hypothesis, we incubated median eminence-pars tuberalis tissue from male rats in vitro. After preincubation in Krebs-Ringer bicarbonate buffer for 30 min, test substances were added to fresh medium and the incubation was continued for 30 min. LHRH or LH released into the medium was measured by radioimmunoassay. Melatonin induced a dose-related release of LHRH with the maximum response at the greatest concentration tested (1 microM). This concentration of melatonin also significantly reduced the release of LH into the medium. The increased release of LHRH induced by melatonin (10 microM) was completely blocked by the addition of LH (50 ng/ml), which by itself had no significant effect on LHRH release. Rat LH antiserum (final dilution, 1:1800) significantly elevated LHRH output, whereas normal rabbit serum at a similar dilution had no effect. Finally, LHRH (0.1 microM) induced a significant release of LH from median eminence-pars tuberalis tissue that was completely blocked by melatonin (10 microM). The results support the hypothesis that LH released from the pars tuberalis diffuses to the LHRH terminals in the median eminence to suppress LHRH release. Melatonin acts on its receptors in the pars tuberalis to inhibit LH release, thereby stimulating the release of LHRH from its terminals in the median eminence. The negative short-loop feedback of LH inhibits basal LHRH release in vitro since antiserum against LH increased LHRH release. The results suggest a concept concerning the mechanism by which melatonin can affect the release of pituitary hormones from the pars tuberalis. It is likely that these pituitary hormones diffuse into the median eminence to modify the release of hypothalamic releasing and inhibiting peptides, thereby altering plasma pituitary hormone concentrations. PMID- 1881899 TI - Integration of DNA fragments by illegitimate recombination in Saccharomyces cerevisiae. AB - DNA fragments (generated by BamHI treatment) with no homology to the yeast genome were transformed into Saccharomyces cerevisiae. When the fragments were transformed in the presence of the BamHI enzyme, they integrated into genomic BamHI sites. When the fragments were transformed in the absence of the enzyme, they integrated into genomic G-A-T-C sites. Since the G-A-T-C sequence is present at the ends of BamHI fragments, this results indicates that four base pairs of homology are sufficient for some types of mitotic recombination. PMID- 1881900 TI - Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice. AB - We describe preliminary studies of the pharmacokinetics, biodistribution, and excretion of an oligodeoxy-nucleotide phosphorothioate ([S]oligonucleotide) in mice. After either intravenous or intraperitoneal administration of a single dose (30 mg/kg of body weight), [S]oligonucleotide (35S-labeled at each internucleotide linkage) was found in most of the tissues for up to 48 hr. About 30% of the dose was excreted in urine within 24 hr, irrespective of the mode of administration; the excreted [S]oligonucleotide was found to be extensively degraded. In plasma, stomach, heart, and intestine, the [S]oligonucleotide was degraded by only 15%, whereas in the kidney and liver degradation was about 50% in 48 hr. The surprising observation was made that chain length extension of administered [S]oligonucleotide occurred in kidney, liver, and intestine. These results provide an initial definition of parameters for the pharmaceutical development of antisense oligonucleotides. PMID- 1881901 TI - A human alcohol dehydrogenase gene (ADH6) encoding an additional class of isozyme. AB - The human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) gene family consists of five known loci (ADH1-ADH5), which have been mapped close together on chromosome 4 (4q21-25). ADH isozymes encoded by these genes are grouped in three distinct classes in terms of their enzymological properties. A moderate structural similarity is observed between the members of different classes. We isolated an additional member of the ADH gene family by means of cross-hybridization with the ADH2 (class I) cDNA probe. cDNA clones corresponding to this gene were derived from PCR-amplified libraries as well. The coding sequence of a 368-amino-acid-long open reading frame was interrupted by introns into eight exons and spanned approximately 17 kilobases on the genome. The gene contains a glucocorticoid response element at the 5' region. The transcript was detected in the stomach and liver. The deduced amino acid sequence of the open reading frame showed about 60% positional identity with known human ADHs. This extent of homology is comparable to interclass similarity in the human ADH family. Thus, the newly identified gene, which is designated ADH6, governs the synthesis of an enzyme that belongs to another class of ADHs presumably with a distinct physiological role. PMID- 1881902 TI - A wild-type DNA ligase I gene is expressed in Bloom's syndrome cells. AB - Alteration of DNA ligase I activity is a consistent biochemical feature of Bloom's syndrome (BS) cells. DNA ligase I activity in BS cells either is reduced and abnormally thermolabile or is present in an anomalously dimeric form. To assess the role of DNA ligase function in the etiology of BS, we have cloned the DNA ligase I cDNA from normal human cells by a PCR strategy using degenerate oligonucleotide primers based on conserved regions of the Saccharomyces cerevisiae and Schizosaccharomyces pombe DNA ligase genes. Human DNA ligase I cDNAs from normal and BS cells complemented a S. cerevisiae DNA ligase mutation, and protein extracts prepared from S. cerevisiae transformants expressing normal and BS cDNA contained comparable levels of DNA ligase I activity. DNA sequencing and Northern blot analysis of DNA ligase I expression in two BS human fibroblast lines representing each of the two aberrant DNA ligase I molecular phenotypes demonstrated that this gene was unchanged in BS cells. Thus, another factor may be responsible for the observed reduction in DNA ligase I activity associated with this chromosomal breakage syndrome. PMID- 1881903 TI - Leukotriene A4 hydrolase: determination of the three zinc-binding ligands by site directed mutagenesis and zinc analysis. AB - Three mutants of recombinant mouse leukotriene A4 (LTA4) hydrolase (3.3.2.6) were produced by site-directed mutagenesis on cDNA. The codons corresponding to His 295, His-299, or Glu-318 were replaced by codons encoding tyrosine, tyrosine, and glutamine, respectively. The mutated cDNAs were expressed in Escherichia coli, and the three mutated proteins were purified to apparent homogeneity. None of these mutants contained significant amounts of zinc, as determined by atomic absorption spectrometry, and all of them were practically devoid of both LTA4 hydrolase and peptidase enzyme activities. Nevertheless, the mutated proteins could be positively identified by their immunoreactivities with an antiserum for human LTA4 hydrolase in immunoblot analysis. Site-directed mutagenesis was also carried out on human LTA4 hydrolase cDNA. Codons encoding His-295, His-299, and Glu-318 were replaced by ones encoding tyrosine, leucine, and alanine, respectively, and the three mutants were expressed in E. coli. The LTA4 hydrolase activities of the total soluble proteins produced in these expressions were less than 10% of that obtained for bacteria harboring nonmutated cDNA. In agreement with earlier predictions, our experimental data demonstrate that His-295, His 299, and Glu-318 constitute the three ligands of the intrinsic zinc atom in LTA4 hydrolase. Additionally, the combined loss of enzyme activities and zinc content in the purified mutated mouse proteins, emphasizes the critical role of the zinc atom for catalysis, whereas the virtually identical chromatographic behaviors of the mutated and nonmutated mouse LTA4 hydrolase proteins suggest that the metal is of limited importance for the maintenance of the enzyme tertiary structure. PMID- 1881904 TI - Detection of human T-lymphotropic virus-like particles in cultures of peripheral blood lymphocytes from patients with mycosis fungoides. AB - Because of seronegativity and absence of a leukemic phase in most patients with mycosis fungoides, a role for the human T-lymphotropic virus type I (HTLV-I) in this disease has remained tenuous. Virus particles are not seen in fresh isolates of skin or blood lymphocytes and the malignant cells (Sezary cells) have been difficult to culture. The availability of growth factors and biomolecular techniques have prompted a renewed attempt to find evidence of virus infection in these patients. We report here the successful culture of blood lymphocytes of 17 patients with mycosis fungoides and 1 patient with the Sezary syndrome. The cells of 2 additional patients failed to grow after 4-6 weeks in vitro. Ultrastructural analysis of the cultures showed an abundance of HTLV-like particles in the specimens of 18 of the 20 patients. Preliminary immunohistochemical studies carried out with various antisera directed against HTLV-I and the polymerase chain reaction utilizing a probe for a conserved region of the pol gene of HTLV-I were positive on only a portion of the specimens. Although definitive characterization of this organism awaits further analysis, it seems likely that circulating lymphocytes of all patients with mycosis fungoides harbor a virus that morphologically resembles HTLV-I. PMID- 1881905 TI - Expression of a partially deleted gene of human type II procollagen (COL2A1) in transgenic mice produces a chondrodysplasia. AB - A minigene version of the human gene for type II procollagen (COL2A1) was prepared that lacked a large central region containing 12 of the 52 exons and therefore 291 of the 1523 codons of the gene. The construct was modeled after sporadic in-frame deletions of collagen genes that cause synthesis of shortened pro alpha chains that associate with normal pro alpha chains and thereby cause degradation of the shortened and normal pro alpha chains through a process called procollagen suicide. The gene construct was used to prepare five lines of transgenic mice expressing the minigene. A large proportion of the mice expressing the minigene developed a phenotype of a chondrodysplasia with dwarfism, short and thick limbs, a short snout, a cranial bulge, a cleft palate, and delayed mineralization of bone. A number of mice died shortly after birth. Microscopic examination of cartilage revealed decreased density and organization of collagen fibrils. In cultured chondrocytes from the transgenic mice, the minigene was expressed as shortened pro alpha 1(II) chains that were disulfide linked to normal mouse pro alpha 1(II) chains. Therefore, the phenotype is probably explained by depletion of the endogenous mouse type II procollagen through the phenomenon of procollagen suicide. PMID- 1881906 TI - Two closely linked Drosophila POU domain genes are expressed in neuroblasts and sensory elements. AB - We have characterized two Drosophila POU genes designated dPOU-19 and dPOU-28. These genes are transcribed as 3.1- and 2.2-kilobase mRNAs, respectively, which accumulate maximally during the first 12 hr of embryogenesis. The mRNAs encode 601- and 475-amino acid deduced proteins; their POU domains are most related to those of the human OCT1 and OCT2. Both genes give similar nervous system expression patterns and map to an indistinguishable site at 33F on the cytological map. Transcription of the genes is first observed in the cellular blastoderm. In the course of embryonic development, expression is observed in the neuroectoderm, with subsets of neuroblasts in the procephalic and germband central nervous system as well as a subset of peripheral nervous system elements. The expression patterns of the two POU genes suggest a possible functional role for these putative transcription factors in neurogenesis and neurospecification. PMID- 1881907 TI - Pore-forming peptide of pathogenic Entamoeba histolytica. AB - A polypeptide that causes pore formation in target-cell membranes is implicated in the potent cytolytic activity of pathogenic Entamoeba histolytica. Pore forming material was purified to apparent homogeneity by a multistep procedure, and its analysis by NaDodSO4/PAGE revealed one peptide of 4-5 kDa under nonreducing or under reducing conditions. Pore-forming activity was measured by depolarization of liposome membrane potential and was found to be optimally expressed at low pH. Active material preferentially inserted into negatively charged lipid vesicles. Treatment of purified amoeba peptide in solution or bound to liposomes with glutaraldehyde revealed oligomers upon NaDodSO4/PAGE, suggesting functionally relevant peptide-peptide interactions. The NH2-terminal amino acid sequence of the amoeba peptide was determined by protein sequencing and revealed a structural similarity to melittin, the membranolytic peptide of bee venom. PMID- 1881908 TI - Acetylcholine receptor-inducing activity stimulates expression of the epsilon subunit gene of the muscle acetylcholine receptor. AB - Motor neurons regulate the transcription of acetylcholine receptor subunit genes in postsynaptic muscle fibers both through muscle electrical activity produced by motor neuron acetylcholine release and by mechanisms independent of such transmitter release. Factors secreted by the motor neuron may mediate activity independent regulation, including the postnatal switch from alpha 2 beta gamma delta (embryonic type) to alpha 2 beta epsilon delta (adult type) receptors. We have investigated the effect of putative trophic factors, agents affecting second messenger systems, and muscle activity on the levels of acetylcholine receptor subunit mRNAs in primary mouse muscle cultures. We found that ARIA (acetylcholine receptor-inducing activity), a 42-kDa glycoprotein purified on the basis of its ability to increase the synthesis of acetylcholine receptors in chick myotubes, increases epsilon-subunit mRNA levels up to 10-fold. In addition, ARIA stimulated alpha-, gamma-, and delta-subunit mRNA levels 2-fold but had no effect on the expression of the beta-subunit gene. These effects of ARIA were independent of muscle activity, and they were not mimicked by calcitonin gene-related peptide nor by thyroxine, forskolin, phorbol 12-myristate 13-acetate, the calcium ionophore A23187, basic fibroblast growth factor, or transforming growth factor beta. Based on these data, we suggest that ARIA may act at the mammalian neuromuscular junction to induce adult-type acetylcholine receptors. PMID- 1881909 TI - Evidence for a factor required for transcriptional stimulation by the chimeric acidic activator GAL-VP16 in HeLa cell extracts. AB - We provide biochemical evidence for the existence of a transcriptional intermediary factor (TIF) in HeLa whole-cell extracts (WCE) that is distinct from the basic transcription factors and that is required for transcriptional stimulation by the chimeric acidic activator GAL-VP16. We have fractionated HeLa WCE by heparin-agarose chromatography. Of transcriptionally active fractions eluting in a step between 0.24 and 0.6 M KCl, the initial fractions are refractory to GAL-VP16 stimulation, whereas subsequent fractions are strongly stimulated by the activator. Aliquots of GAL-VP16-responsive fractions efficiently complement refractory fractions for transcriptional stimulation. Aliquots of responsive fractions are also far more efficient than those of refractory fractions in overcoming transcriptional inhibition that is brought about by high concentrations of GAL-VP16. Experiments performed with heat-treated WCE support the idea that HeLa cells contain a TIF that is essential for GAL-VP16 stimulation, but that is not required for basal transcription. Addition of recombinant yeast or human transcription factor TFIID (rTFIIDY and rTFIIDH, respectively) to a WCE heated at 48 degrees C for 15 min restores basal transcription, but in neither case is the reconstituted system activated by GAL VP16. However, a 45 degrees C heat-treated WCE reconstituted with either rTFIIDH or rTFIIDY is stimulated by GAL-VP16, suggesting that a HeLa TIF can be selectively inactivated by heating at 48 degrees C, but not at 45 degrees C. Interestingly, a TFIID fraction partially purified from HeLa cell extracts, but not rTFIIDH, efficiently relieves transcriptional inhibition by GAL-VP16, suggesting that there may be an association between TIF(s) and TFIID and, moreover, that TIF(s) may be the direct target of the acidic domain of GAL-VP16. In summary, our results support the existence of a TIF that is not essential for basal transcription but that is required to mediate the stimulatory activity of the acidic activator GAL-VP16. PMID- 1881910 TI - Recombination by sequence repeats with formation of suppressive or residual mitochondrial DNA in Neurospora. AB - Recombination junctions of several Neurospora mitochondrial DNA (mtDNA) mutants and their revertants were identified. Their nucleotide sequences and putative secondary structures were determined in order to understand the nature of the elements involved in intramolecular recombination. Multiple deletions, involving the same portion of Neurospora mtDNA, were identified in six independently isolated mutants. A 9-nucleotide repeat element, CCCCNCCCC, was found to be involved in these and other Neurospora mitochondrial recombination events. The repeat elements were clustered as hot spots on the Neurospora mtDNA and were associated with palindromic DNA sequences. The palindromes have a potential to generate hairpin structures. A much lower free energy of the putative hairpins at the 5' end of the recombination site, and the possible formation of non-B-DNA structure by polypyrimidine tracks, may be important in the initiation of recombination. Using PCR, we found low levels of a specific mitochondrial deletion in certain Neurospora mutants. Their presence in low amounts in a population with a much larger number of normal mtDNA is unexpected. Contrary to earlier belief, this finding supports the view that deleted, smaller DNA molecules are not always suppressive relative to normal mtDNAs. PMID- 1881911 TI - Involvement of the interleukin 4 pathway in the generation of functional gamma delta T cells from human pro-T cells. AB - We have used the technique of in situ hybridization to investigate the transcription of genes encoding the CD3 complex and the lymphokine interleukin 4 (IL-4) by human pro-T cells--i.e., cells that phenotypically resemble those T cell precursors that colonize the thymus during early intrathymic development. CD1-2-3-4-7+8-45+ pro-T cells isolated from postnatal thymi via immunoselection with a panel of specific monoclonal antibodies are already committed to the T cell lineage because most of them transcribe the genes encoding the delta and epsilon chains of the CD3 complex. About half of such pro-T cells synthesize IL-4 mRNA in the absence of any exogenous stimulation. Upon culture with IL-4, pro-T cells extensively proliferate and differentiate into functionally competent, mature gamma delta T cells expressing a T-cell receptor repertoire similar to that of gamma delta T cells that can be found in postnatal thymus. The IL-4 response of pro-T cells is not mediated by induction of the interleukin 2 (IL-2) IL-2 receptor pathway and, unlike IL-2-driven T-cell differentiation, does not require the presence of stromal cells. Taken altogether, these findings suggest that an autocrine IL-4-mediated pathway might be implicated in early thymocyte differentiation--namely, in the generation of T cells bearing the gamma delta T cell receptor. PMID- 1881913 TI - I-TevI, the endonuclease encoded by the mobile td intron, recognizes binding and cleavage domains on its DNA target. AB - Mobility of the phage T4 td intron depends on activity of an intron-encoded endonuclease (I-TevI), which cleaves a homologous intronless (delta In) target gene. The double-strand break initiates a recombination event that leads to intron transfer. We found previously that I-TevI cleaves td delta In target DNA 23-26 nucleotides upstream of the intron insertion site. DNase I-footprinting experiments and gel-shift assays indicate that I-TevI makes primary contacts around the intron insertion site. A synthetic DNA duplex spanning the insertion site but lacking the cleavage site was shown to bind I-TevI specifically, and when cloned, to direct cleavage into vector sequences. The behavior of the cloned duplex and that of deletion and insertion mutants support a primary role for sequences surrounding the insertion site in directing I-TevI binding, conferring cleavage ability, and determining cleavage polarity. On the other hand, sequences around the cleavage site were shown to influence cleavage efficiency and cut-site selection. The role of cleavage-site sequences in determining cleavage distance argues against a strict "ruler" mechanism for cleavage by I-TevI. The complex nature of the homing site recognized by this unusual type of endonuclease is considered in the context of intron spread. PMID- 1881912 TI - Highly divergent molecular variants of human T-lymphotropic virus type I from isolated populations in Papua New Guinea and the Solomon Islands. AB - To determine the molecular genetic relationship between Melanesian strains of human T-lymphotropic virus type I (HTLV-I) and cosmopolitan prototype HTLV-I, we amplified by PCR, then cloned, and sequenced a 522-base-pair region of the HTLV-I env gene in DNA extracted from uncultured (fresh) and cultured peripheral blood mononuclear cells obtained from six seropositive Melanesian Papua New Guineans and Solomon Islanders, including a Solomon Islander with HTLV-I myeloneuropathy. Unlike isolates of HTLV-I from Japan, the West Indies, the Americas, and Africa, which share greater than or equal to 97% sequence homology, the Melanesian strains of HTLV-I were only 91.8%-92.5% identical with a prototype Japanese HTLV IATK-1. The nucleotide sequence of proviral DNA from the Solomon Islander with HTLV-I myeloneuropathy also diverged markedly from that of HTLV-I isolated from Japanese patients with HTLV-I-associated myelopathy and from Jamaican patients with tropical spastic paraparesis, suggesting that these variant viruses are capable of causing disease. The HTLV-I variants from Papua New Guineans, in turn, differed by nearly 4% from the Melanesian variants from Solomon Islanders, indicating the existence of another HTLV-I quasi-species. By contrast, HTLV-I strains from two residents of Bellona Island, a Polynesian Outlier within the Solomon Islands, were closely related to cosmopolitan prototype HTLV-I (greater than or equal to 97% sequence identity), suggesting recent introduction, possibly during this century. These findings are consistent with a proto-Melanesian HTLV-I strain of archaic presence, which evolved independently of contemporary cosmopolitan strains, and pose new questions about the origin and global dissemination of HTLV-I. PMID- 1881914 TI - Separation of transcriptional activation and silencing functions of the RAP1 encoded repressor/activator protein 1: isolation of viable mutants affecting both silencing and telomere length. AB - The repressor/activator protein 1 (RAP1) binds to the upstream activating sites of many genes, the silencer elements flanking the unexpressed mating-type loci HMR and HML, and the poly(C1-3A) sequences at telomeres, suggesting that RAP1 might have three distinct regulatory functions. To determine the in vivo role of RAP1 in repression of the HMR silent locus, we developed a screen to isolate rap1 mutants specifically defective in silencing. Fifteen independent mutants defining four different rap1 alleles were isolated. These alleles are defective to different extents in repression of an HMR locus containing a mutated, but fully functional, silencer. All four alleles are missense mutations in only three codons within a small C-terminal region of the gene. These silencing-defective mutants have no apparent growth defects, indicating that expression of the large number of essential genes that have promoters containing RAP1-binding sites is normal. A transcriptional silencing function of RAP1 can therefore be genetically separated from its presumably essential activation functions. Surprisingly, three of the silencing-defective rap1 alleles have significantly longer telomeres, suggesting that the function of RAP1 in both transcriptional silencing and telomere-length regulation may be related. In addition, we have demonstrated that increased gene dosage of either SIR1 or SIR4, two other factors required for silencing, suppresses the silencing defect of the rap1 mutants. The properties of SIR4 dosage suppression suggest that SIR4 protein may interact directly with RAP1 at silencers. PMID- 1881915 TI - Integrative selection of human chromosome-specific yeast artificial chromosomes. AB - Human specific "integrative selection vectors" (ISVs) were designed to optimize integration of a yeast-selectable marker specifically into yeast artificial chromosomes (YACs) derived from human but not mouse DNA. ISVs were transformed into a YAC genomic library constructed from DNA of a human-mouse somatic cell hybrid containing chromosome 21 (HSA21) as the only human chromosome. One percent of the yeast in the original library contained HSA21-derived YACs; between 45% and 54% of the yeast recovered after transformation with ISV vectors contained human YACs. Integrative selection provides a rapid means of obtaining a highly enriched population of human chromosome-specific YACs by eliminating the labor intensive steps of isolating and screening primary transformants. The procedure is biased toward the selection of YACs that contain a large number of targets for homologous recombinations; thus, libraries constructed by this procedure will be composed primarily of the largest YACs in the population. PMID- 1881917 TI - Translocation of the glucose transporter GLUT4 in cardiac myocytes of the rat. AB - The insulin-regulated glucose transporter GLUT4 was immunolocalized in rat cardiac muscle under conditions of basal and stimulated glucose uptake, achieved by fasting and a combined exercise/insulin stimulus, respectively. In basal myocytes there was very little (less than 1%) GLUT4 in the different domains of the plasma membrane (sarcolemma, intercalated disk, and transverse tubular system). GLUT4 was localized in small tubulo-vesicular elements that occur predominantly near the sarcolemma and the transverse tubular system and in the trans-Golgi region. Upon stimulation approximately 42% of GLUT4 was found in the plasma membrane. Each domain of the plasma membrane contributed equally to this effect. GLUT4-positive, clathrin-coated pits were also present at each cell surface domain. The remainder of the labeling was in tubulo-vesicular elements at the same sites as in basal cells and in the intercalated disk areas. The localization of GLUT4 in cardiac myocytes is essentially the same as in brown adipocytes, skeletal muscle, and white adipocytes. We conclude that increased glucose transport in muscle and fat is accounted for by translocation of GLUT4 from the intracellular tubulo-vesicular elements to the plasma membrane. The labeling of coated pits indicates that in stimulated myocytes, as in adipocytes, GLUT4 recycles constantly between the endosomal compartment and the plasma membrane and that stimulation of the exocytotic rate constant is likely the major mechanism for GLUT4 translocation. PMID- 1881916 TI - Rat obesity gene fatty (fa) maps to chromosome 5: evidence for homology with the mouse gene diabetes (db). AB - The autosomal recessive mutations fa (rat) and db (mouse) cause obesity syndromes that develop early and ultimately become severe. Although both fa/fa rats and db/db mice have been studied extensively as models of human obesity and diabetes, the molecular bases of these phenotypes remain unknown. We have mapped fa in 50 fa/fa (obese) offspring of a (13M x Brown Norway) F1 fa/+ intercross relative to two molecular markers, Ifa and Glut-1, which flank db on mouse chromosome 4 and which are located on rat chromosome 5. Ifa and Glut-1 are linked to fa, with a gene order, Ifa-fa-Glut-1, that is identical to that for the region around db in the mouse genome. These results place fa on rat chromosome 5 and suggest that db and fa are mutations in homologous genes. PMID- 1881918 TI - Suppressed intrinsic catalytic activity of GLUT1 glucose transporters in insulin sensitive 3T3-L1 adipocytes. AB - Previous studies indicated that the erythroidtype (GLUT1) glucose transporter isoform contributes to basal but not insulin-stimulated hexose transport in mouse 3T3-L1 adipocytes. In the present studies it was found that basal hexose uptake in 3T3-L1 adipocytes was about 50% lower than that in 3T3-L1 or CHO-K1 fibroblasts. Intrinsic catalytic activities of GLUT1 transporters in CHO-K1 and 3T3-L1 cells were compared by normalizing these hexose transport rates to GLUT1 content on the cell surface, as measured by two independent methods. Cell surface GLUT1 levels in 3T3-L1 fibroblasts and adipocytes were about 10- and 25-fold higher, respectively, than in CHO-K1 fibroblasts, as assessed with an anti-GLUT1 exofacial domain antiserum, delta. The large excess of cell surface GLUT1 transporters in 3T3-L1 adipocytes relative to CHO-K1 fibroblasts was confirmed by GLUT1 protein immunoblot analysis and by photoaffinity labelling (with 3 [125I]iodo-4-azidophenethylamido-7-O-succinyldeacetylforskoli n) of glucose transporters in isolated plasma membranes. Thus, GLUT1 intrinsic activity is markedly reduced in 3T3-L1 fibroblasts compared with the CHO-K1 fibroblasts, and further reduction occurs upon differentiation to adipocytes. Intrinsic catalytic activities specifically associated with heterologously expressed human GLUT1 protein in transfected CHO-K1 versus 3T3-L1 cells were determined by subtracting appropriate control cell values for hexose transport and delta-antibody binding from those determined in the transfected cells expressing high levels of human GLUT1. The results confirmed a greater than 90% inhibition of the intrinsic catalytic activity of human GLUT1 transporters on the surface of mouse 3T3-L1 adipocytes relative to CHO-K1 fibroblasts. We conclude that a mechanism that markedly suppresses basal hexose transport catalyzed by GLUT1 is a major contributor to the dramatic insulin sensitivity of glucose uptake in 3T3-L1 adipocytes. PMID- 1881919 TI - A close relative of the nuclear, chromosomal high-mobility group protein HMG1 in yeast mitochondria. AB - ABF2 (ARS-binding factor 2), a small, basic DNA-binding protein that binds specifically to the autonomously replicating sequence ARS1, is located primarily in the mitochondria of the yeast Saccharomyces cerevisiae. The abundance of ABF2 and the phenotype of abf2- null mutants argue that this protein plays a key role in the structure, maintenance, and expression of the yeast mitochondrial genome. The predicted amino acid sequence of ABF2 is closely related to the high-mobility group proteins HMG1 and HMG2 from vertebrate cell nuclei and to several other DNA binding proteins. Additionally, ABF2 and the other HMG-related proteins are related to a globular domain from the heat shock protein hsp70 family. ABF2 interacts with DNA both nonspecifically and in a specific manner within regulatory regions, suggesting a mechanism whereby it may aid in compacting the mitochondrial genome without interfering with expression. PMID- 1881920 TI - Mapping of human microtubule-associated protein 1B in proximity to the spinal muscular atrophy locus at 5q13. AB - A polyclonal antiserum directed against the C-terminal domain of dystrophin was used to isolate a cDNA clone encoding an antigenically cross-reactive protein, microtubule-associated protein 1B (MAP-1B). Physical mapping of the human MAP-1B locus places its chromosomal location at 5q13, in proximity to the spinal muscular atrophy (SMA) locus. SMA is a degenerative disorder primarily affecting motor neurons. Genetic linkage analysis of SMA families using a human dinucleotide repeat polymorphism just 3' of the MAP-1B gene has shown tight linkage to SMA mutations. These mapping data together with the postulated role of MAP-1B in neuronal morphogenesis and its localization in anterior horn motor neurons suggest a possible association with SMA. PMID- 1881921 TI - T-cell-receptor-independent activation of cytolytic activity of cytotoxic T lymphocytes mediated through CD44 and gp90MEL-14. AB - CD44 is a transmembrane glycoprotein found on a variety of cells including those of myeloid and lymphoid origin. CD44 is highly conserved among various species and is involved in the homing of lymphocytes and monocytes to lymph nodes, Peyer's patches, and sites of inflammation. In the present study, we demonstrate that monoclonal antibody (mAb) 9F3, directed against murine phagocytic glycoprotein 1 (CD44) expressed on cytotoxic T lymphocytes (CTLs), can trigger the lytic activity of CTLs and redirect CTL-mediated lysis to antigen-negative Fc receptor-positive target cells. Similar redirected lysis was also inducible using mAb MEL-14, directed against the lymphocyte homing receptor for endothelium (gp90MEL-14). The redirected lysis induced by mAbs 9F3 and MEL-14 was similar to that induced by mAbs against the alpha beta T-cell receptor or CD3. In contrast, mAbs directed against CD8, CD45R, and CD11a (LFA-1, lymphocyte function associated antigen 1) failed to evoke lytic activity. The current study demonstrates that CD44 and gp90MEL-14 molecules, in addition to participating in T-cell homing and adhesion, may play a major role in delivering the transmembrane signal to the CTL that triggers the lytic activity, even when the T-cell receptor is not occupied. Such a mechanism may account for the nonspecific tissue damage seen at sites of CTL-mediated inflammation. PMID- 1881922 TI - Amino acid substitutions in the coat protein result in loss of insect transmissibility of a plant virus. AB - Amino acids near the N terminus of the coat protein of tobacco vein mottling virus were deleted or altered by site-directed mutagenesis to determine the effect on aphid transmissibility of the virus. Deletion of a three amino acid sequence Asp-Ala-Gly, which is conserved in aphid-transmissible potyvirus isolates, abolished transmission. The mutation Ala----Thr in this triplet drastically reduced transmission, whereas the mutation Asp----Asn had no effect, and the mutation Asp----Lys consistently reverted to the wild-type residue. The mutation Lys----Glu, in the residue adjacent to the glycine of the triplet, drastically reduced transmission, whereas the mutation Gln----Pro, seven residues downstream from the glycine had no effect. Comparison of the sequences of other potyviruses suggests that the presence of a glycine residue at the third position of the Asp-Ala-Gly triplet is critical for aphid transmissibility and that certain changes in the residues adjacent to this position abolish or greatly reduce aphid transmissibility. PMID- 1881923 TI - Micromotion of mammalian cells measured electrically. AB - Motility is a fundamental property of mammalian cells that normally is observed in tissue culture by time lapse microscopy where resolution is limited by the wavelength of light. This paper examines a powerful electrical technique by which cell motion is quantitatively measured at the nanometer level. In this method, the cells are cultured on small evaporated gold electrodes carrying weak ac currents. A large change in the measured electrical impedance of the electrodes is observed when cells attach and spread on these electrodes. When the impedance is tracked as a function of time, fluctuations are observed that are a direct measure of cell motion. Surprisingly, these fluctuations continue even when the cell layer becomes confluent. By comparing the measured impedance with a theoretical model, it is clear that under these circumstances the average motions of the cell layer of 1 nm can be inferred from the measurements. We refer to this aspect of cell motility as micromotion. PMID- 1881924 TI - Does the Nutrition Society serve the needs of its overseas members? PMID- 1881925 TI - Development of food choice during infancy. PMID- 1881926 TI - Assessment of zinc status. PMID- 1881928 TI - Nutrition education in Scottish schools. PMID- 1881927 TI - Food, vitamins and IQ. PMID- 1881929 TI - Food choices and preferences of schoolchildren. PMID- 1881930 TI - Diet selection by animals: theory and experimental design. PMID- 1881932 TI - Diet selection--an ecological perspective. PMID- 1881931 TI - Mechanisms of diet selection: the translation of needs into behaviour. PMID- 1881933 TI - Diet selection by grazing animals. PMID- 1881934 TI - Diet selection of pigs and poultry. PMID- 1881935 TI - The assessment of zinc status: a personal view. PMID- 1881937 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 1881936 TI - Sensory and experiential factors in the design of foods for domestic dogs and cats. PMID- 1881938 TI - Prostaglandin release by normal and osteomyelitic human bones. AB - The release of prostaglandin E (PGE) and prostacyclin (as 6-keto PGF1 alpha) by human osteomyelitic bone, compared with normal (control) bone, incubated in vitro was evaluated. Prostacyclin was the main arachidonic acid metabolite released by normal human bone, and similar quantities were released by osteomyelitic bone. However, PGE production was 5-30-fold higher in osteomyelitic bone, compared with control, thus becoming the major prostanoid in this disease. It is concluded that PGE production is probably involved in the inflammatory and/or bone resorption processes that occur in osteomyelitis. PMID- 1881939 TI - The effects of ovarian steroids in controlling rat uterine prostaglandin F2-alpha during the peri-implantation period. AB - Rats with delayed implantation, induced by ovariectomy or hypophysectomy, as well as those with normal pregnancy were used to examine the changes in uterine prostaglandin F2 alpha (PGF2 alpha) associated with implantation. In normal pregnant rats, while maximal uterine production of PGF2 alpha was found at 09:00, maximal catabolic enzyme activity (CEA) was seen at 17:00 of day 4. Uterine content of PGF2 alpha was high at 17:00 of day 4, but decreased by 80% within the next 24 h. There was no change in PGF2 alpha production during the first 6 h after injection of estradiol to hypophysectomized animals. There was, however, a dramatic decrease in production within the next 6 h. In contrast, CEA was not different in animals treated with estrogen than in those receiving only progesterone. In ovariectomized animals, uterine PGF2 alpha production also was lowered by estrogen but in these animals CEA was significantly elevated 18 h after injection of estradiol. Estrogen caused a greater increase in PGF2 alpha content in the hypophysectomized, compared to the ovariectomized, rats. The results are consistent with the view that ovarian steroids play an important role in controlling the changes in uterine PGF2 alpha around the time of implantation in rat. PMID- 1881940 TI - A product of activated human granulocytes stimulates prostaglandin E2 synthesis in human amnion cells. AB - Cell-free supernatant from formylmethionyl-leucyl-phenylalanine (fMLP)-activated granulocytes causes a time- and concentration-dependent stimulation of prostaglandin E2 (PGE2) production in amnion cells. PGE2 concentration in the culture medium after 36 h treatment with granulocyte supernatant (from 40 x 10(6) granulocytes/ml of amnion cell medium), 1.49 +/- 0.71 pg/ng DNA (n = 13), was significantly higher (p = 0.0015) than in control cells (0.33 +/- 0.23 pg/ng DNA, n = 13). Indomethacin abolished this stimulation. Granulocyte supernatant and human epidermal growth factor (hEGF) had an additive effect on amnion cell PGE2 production. Catalase, superoxide dismutase (SOD), protease inhibitors or the platelet-activating factor (PAF) antagonist L-659,989 had no effect. Actinomycin D, cycloheximide and mepacrine reduced the PGE2 production. The phospholipase A2 activity present in granulocyte supernatants was resistant to heating, whereas heating decreased their PGE2-stimulating activity by 92%. Exogenous phospholipase A2 had no effect on PGE2 synthesis. The granulocyte product could be precipitated with ammonium sulphate. On gel filtration of supernatant, two peaks of PGE2 synthesis stimulating activity were obtained (molecular weights 12,000 and 60,000). This data serve to explain the association of chorioamnionitis with preterm labor: activated granulocytes release a protein(s) that induces prostaglandin production in amnion cells, and thus promote labor. PMID- 1881941 TI - The effect of gamma-linolenic acid and zinc supplementation on the growth of normal and tumour cells in vitro. AB - The effects of zinc, gamma-linolenic acid (GLA) and zinc combined and GLA supplementations on the growth of a benign monkey kidney, cell line (LLCMK) and a malignant tumour murine melanoma, cell line (BL-6) cells in vitro were studied. Cell growth was indicated by both cell counts and 3H-thymidine incorporation into DNA. The addition of zinc to the cells resulted in a general trend of overall reduction in the growth of tumour cells but not in the normal cells. The addition of GLA at high concentrations resulted in a general decrease in cell growth of both the benign and malignant tumour cells while the addition of lower concentrations of GLA had less effect. The combined effect of supplementary zinc and GLA resulted in an inhibitory effect on the growth of the malignant cells while a less and variable effect on the non-malignant cells was found. Some interaction between zinc and GLA in reducing tumour cell growth is suggested by the results. PMID- 1881942 TI - Effect of dietary nucleotides and orotate on the blood levels of prostacyclin (PGI2) and thromboxane (TXA2) in the weanling rat. AB - Dietary nucleotides affect the maintenance of immune responses, tissue repair and polyunsaturated fatty acid metabolism. Orotate, a pyrimidine nucleotide precursor, induces fatty livers by impairing VLDL hepatic secretion. The aim of this study was to evaluate the changes in the blood levels of fatty acids and prostacyclin (PGI2) and thromboxane (TXA2) in the weanling rat caused by the dietary intake of nucleotides and orotate. Three groups of rats at weaning were fed a control diet, an orotate supplemented diet (O-50) and a nucleotide supplemented diet (N-50) during 4 weeks, respectively. Absolute values of plasma polyunsaturated fatty acids greater than 18 carbon atoms of the n-6 and n-3 series were increased in the N-50 group and decreased in O-50 with regard to the control. However, the relative fatty acid composition of plasma lipid fractions was mostly unaffected. Plasma 6-keto-PGF1 alpha showed a trend to be increased in N-50 and serum TXB2 was significantly increased in that group. Both eicosanoids were unchanged by dietary orotate intake. These results may be explained because of the increased plasma 20:4n-6 found in rats fed a supplemented nucleotide diet. Thus, nucleotides present in foods appear to modulate PUFA conversion and eicosanoids synthesis in early life. PMID- 1881943 TI - Increased production of 15-hydroxyeicosatetraenoic acid by placentae from pregnancies complicated by pregnancy-induced hypertension. AB - Placentae from pregnancies complicated by pregnancy-induced hypertension (PIH) secrete significantly more 15-hydroxyeicosatetraenoic acid (15-HETE) than gestation-matched controls. 15-HETE and its hydroperoxy precursor can inhibit prostacyclin biosynthesis and may thus contribute to the pathological sequelae of PIH. PMID- 1881944 TI - Studies on dressings for dental surgery use. Part 1: Effect of plasticizers on gelatin gel etching rate. AB - For quantitative evaluation of the absorption rate of dental dressings made of gelatin, a biopharmaceutical model of etching of gelatin gels in vitro has been elaborated. For the optimum etching conditions of gelatin gel columns 900 BAEE units per ml trypsin solution was used at a temperature of 25 degrees C. It has been found, that addition of glycerol and propylene glycol insignificantly reduces the etching rate of gelatin gels, whereas the PEG 400, PEG 1500 and PVAL increase resistance of the gels against the etching action of trypsin. In the model provided well repeatable results the coefficient of variation of the average gel etching rate remained within the range of 0.45-0.57%. PMID- 1881945 TI - Isolation and characterization of a thrombin inhibitor from the tick ixodes ricinus. AB - The secretion of the salivary glands of ticks, Ixodes ricinus, contains anticoagulant substances. Some years ago an antithromboplastin, ixodin, was described. The present paper refers the isolation and characterization of a second anticoagulant substance of the ticks named ixin. Ixin proved to be a relatively stable and specific thrombin inhibitor. The multi step procedure for isolation results in a 850-fold purification. The preparation obtained has a specific activity of 250 antithrombin units/mg. It is not homogeneous and still contaminated. The substance was assumed to be a miniprotein. PMID- 1881947 TI - [Micromethod for determination of theophylline/caffeine and chloramphenicol in plasma with HPLC]. PMID- 1881946 TI - Verapamil and the synthesis of prostacyclin in human veins. AB - The synthesis of the vasodilator prostacyclin (PGI2) depends on the intracellular calcium concentration. For this reason the purpose of this study was to document the effects of verapamil (1), a slow calcium channel blocking agent on venous tissue. Human varicose veins were studied which were removed by a stripping operation. The veins were investigated ex vivo and in vitro. For ex vivo studies 11 patients were given 0.01 g 1 i.v. during the operation. In vitro experiments were carried out by an addition of 22 mumol/l 1 to the incubate. The synthesis of PGI2 was studied according to the inhibition of the ADP induced platelet aggregation without and with addition of substrate (prostaglandin endoperoxide H2). 1 did not induce changes in the synthesis of PGI2, neither after administration to patients nor after addition to the incubation fluid compared to control vessels without addition of 1. PMID- 1881948 TI - [Measurement of bromsulfalein retention in the mouse as a possible parameter for assessment of liver function after administration of liposomal preparations]. PMID- 1881950 TI - [Comparison of the biotransformation of the trapidil (Rocornal) derivative AR 12463 in humans, rats, dogs, and rabbits]. PMID- 1881949 TI - In vitro transport of ephedrine from matrix based transdermal formulations. PMID- 1881952 TI - [Pharmacologic modulation of central noradrenergic mechanisms an the effect of selected substances on chemically induced seizures: strychnine-seizure test (mouse)]. PMID- 1881951 TI - [Does vascular endothelium have different transport systems for adenosine and inosine?]. PMID- 1881953 TI - AIDS and the exodus. PMID- 1881954 TI - Chronic dermal ulcer healing enhanced with monophasic pulsed electrical stimulation. AB - The purposes of this randomized, double-blind, multicenter study were to compare healing of chronic dermal ulcers treated with pulsed electrical stimulation with healing of similar wounds treated with sham electrical stimulation and to evaluate patient tolerance to the therapeutic protocol. Forty-seven patients, aged 29 to 91 years, with 50 stage II, III, and IV ulcers were randomly assigned to either a treatment group (n = 26) or a control (sham treatment) group (n = 24). Treated wounds received 30 minutes of pulsed cathodal electrical stimulation twice daily at a pulse frequency of 128 pulses per second (pps) and a peak amplitude of 29.2 mA if the wound contained necrotic tissue or any drainage that was not serosanguinous. A saline-moistened nontreatment electrode was applied 30.5 cm (12 in) cephalad from the wound. This protocol was continued for 3 days after the wound was debrided or exhibited serosanguinous drainage. Thereafter, the polarity of the treatment electrode on the wound was changed every 3 days until the wound progressed to a stage II classification. The pulse frequency was then reduced to 64 pps, and the treatment electrode polarity was changed daily until the wound was healed. Patients in the control group were treated with the same protocol, except they received sham electrical stimulation. After 4 weeks, wounds in the treatment and control groups were 44% and 67% of their initial size, respectively. The healing rates per week for the treatment and control groups were 14% and 8.25%, respectively. The results of this study indicate that pulsed electrical stimulation has a beneficial effect on healing stage II, III, and IV chronic dermal ulcers. PMID- 1881955 TI - An ethical analysis of physical therapists' duty to treat persons who have AIDS: homosexual patients as a test case. AB - A possible abrogation of the health professional's usual duty to treat sometimes is suggested in regard to patients with acquired immunodeficiency syndrome (AIDS). The issue first arose and continues to be discussed in regard to those patients who have contracted AIDS through homosexual encounters, though there are now additional populations of patients with AIDS to whom the issue is being directed as well. We examine three lines of reasoning that may be advanced to support this view: the argument from morality, the argument from responsibility, and the argument from the alleged danger to others. We show logical and ethical shortcomings in each view and suggest how the physical therapist's duty to treat all patients who have AIDS can be realized in a safe and supportive environment. PMID- 1881956 TI - Normal hip and knee active range of motion: the relationship to age. AB - Abnormal joint mobility is an important factor in movement dysfunction and physical disability. Because the decision to treat impaired joint mobility in an older individual may be influenced by assumptions concerning normal range of motion (ROM) at older ages, it is important to establish population-based normative values for hip and knee ROM by age, race, and sex. This study used data from the first National Health and Nutrition Examination Survey (NHANES 1), which involved a national probability sample of persons drawn from the civilian noninstitutionalized population of the United States. Goniometric measurements of hip and knee active range of motion (AROM) were obtained from a subset of the sample consisting of 1,892 subjects. This analysis was limited to the 1,313 white and 370 black subjects. Univariate statistics, weighted by the probability of selection into the sample, were calculated for 12 sex-race-age-group-specific categories. These normal AROM values for the hip and knee calculated from this population based sample were found to differ from estimates found in textbooks by as much as 18 degrees. With one exception, normal values for all motions were lower in the oldest age group than in the youngest age group. The differences in mean AROM were generally small, ranging from 3 to 5 degrees. Only in the case of hip extension did the difference in mean AROM between the youngest and the oldest age groups constitute a decline of more than 20% of the arc of motion. With the possible exception of hip extension, this study supports the conclusion that, at least to age 74 years, any substantial loss of joint mobility should be viewed as abnormal and not attributable to aging and therefore should be treated much as it would be in a younger individual. PMID- 1881957 TI - Effects of ultrasound and trolamine salicylate phonophoresis on delayed-onset muscle soreness. AB - The purpose of this study was to determine the effects of ultrasound and phonophoresis using an anti-inflammatory-analgesic cream (trolamine salicylate) on delayed-onset muscle soreness (DOMS). Repeated eccentric contractions were used to induce DOMS in the elbow flexors of 40 college-aged women. Subjects were then assigned randomly to one of four groups: (1) group 1 (n = 10) received sham ultrasound using placebo cream, (2) group 2 (n = 10) received sham ultrasound using trolamine salicylate cream, (3) group 3 (n = 10) received ultrasound using placebo cream, and (4) group 4 (n = 10) received ultrasound using trolamine salicylate cream. Subjects were treated on 3 consecutive days. Muscle soreness and active elbow range of motion were assessed daily prior to each treatment. The subjects in group 3 experienced an increase in DOMS, whereas no increase in soreness was observed in the subjects in group 4. The authors concluded that ultrasound enhanced the development of DOMS but that this enhancement was offset by the anti-inflammatory-analgesic action of salicylate phonophoresis. These findings suggest that salicylate phonophoresis may be useful in clinical situations in which it is desirable to administer ultrasound without increasing inflammation. PMID- 1881958 TI - Grading written essays: a reliability study. AB - The purpose of this study was to examine the interrater reliability of grades obtained by physical therapy and occupational therapy tutors in rating their students' term papers. This study was carried out in two phases. In phase 1, four student essay papers (two physical therapy students' papers and two occupational therapy students' papers) with grades that had been assigned from the previous year's course were randomly selected from a bank of papers. These papers were independently rated by three course planners (who were responsible for planning, coordinating, and tutoring in the course), and agreement as to the assignment of grades for each paper was established. In phase 2, the same students' essays were rated independently by eight course tutors. To test for differences among students' written essay papers and for differences among the raters in the subcategories of discipline (physical therapy versus occupational therapy) and level of expertise (novice versus experienced) in grading essays, a three-way analysis of variance was performed. An intraclass correlation coefficient (ICC) was calculated for interrater reliability. Although there were no statistically significant differences among the tutors with regard to their discipline and expertise, the reliability analysis produced an ICC of .79. Strategies to enhance the reliability of grading essays are discussed. PMID- 1881959 TI - Singlet and triplet reactivity in the photoreduction of oxonine(3,7 diaminophenoxazin-5-ium chloride) by iron (II). AB - The oxazine dye, oxonine (3,7-diaminophenoxazin-5-ium chloride), 1, is photoreduced by Fe (II) sulfate in dilute sulfuric acid. The reaction mechanism is analogous to that for the photo-reduction of thiazine dyes by Fe (II), the most important difference being that reduction of oxonine occurs predominantly from its excited singlet state, S1, rather than from the triplet state, T1. The latter is formed with an intersystem crossing (isc) quantum yield of ca 1.7 x 10( 3). The quenching of S1 by Fe (II) has a rate constant kSQ = 2.2 +/- 0.1 x 10(9) M-1 s-1 and affords the one electron reduced product, semioxonine (R), with a limiting quantum yield, phi SR, of 0.26 +/- 0.02. In contrast, quenching of T1, generated by bromide ion quenching of S1 or by diacetyl sensitization, occurs with KTQ approximately 1.2 x 10(6) M-1 s-1, extrapolated to zero ionic strength, and affords R with a limiting probability, phi TR = 1.1 +/- 0.2. Three possible reasons for the lower quantum yield of the more exothermic S1 reduction are discussed. These are energy transfer from S1 to Fe (II), different rates of escape of R from the encounter complex as a consequence of the different states of protonation of R as initially formed from S1 and T1, and spin allowed back electron transfer in an exciplex formed between S1 and Fe (II). Evidence is also presented for a very low probability (ca 1%) induced isc from the encounter of S1 with paramagnetic Fe (II). Rate parameters for other processes important to the overall reduction mechanism such as disproportionation of R to leucooxonine L and oxonine, k(R)DIS = 1.7 +/- 0.2 x 10(9) M-1 s-1, oxidation of R by Fe (III), k(R)OX = 1.5 +/- 0.1 x 10(5) M-1 s-1, and oxidation of L by Fe (III), kLOX = 1.1 +/- 0.1 x 10(3) M-1 s-1, have also been measured. These results are contrasted with those for the closely related thionine/Fe(II) photoredox reaction, the most well understood system for photogalvanic energy conversion. PMID- 1881960 TI - Ring opening photoreactions of 5-bromouracil and 5-bromo-2'-deoxyuridine with selected alkylamines. AB - Several studies in the literature indicate that histones (lysine rich proteins found associated with DNA in eukaryotic chromatin), as well as poly-L-lysine, can be photocross-linked by ultraviolet (UV) light to DNA in which 5-bromo-2' deoxyuridine has been substituted for thymidine. To gain some insight into the possible nature of this cross-linking, we have studied the photoreactions occurring in deoxygenated aqueous solutions containing 5-bromouracil (I) (BrUra) or 5-bromo-2'-deoxyuridine (III) (BrdUrd) and ethylamine, a lysine side chain analog. In the case of I this reaction produced the ring opened compound N-(N' ethylcarbamoyl)-3-amino-2-bromoacrylamide (Ia). A small amount of N-(N' ethylcarbamoyl)-3-ethylamino-2-bromoacrylamide (Ic) was also isolated. It was found that purified Ia, standing in the presence of ethylamine, was gradually converted to Ic in a dark reaction. The beta and alpha anomers of N-(N' ethylcarbamoyl)-3-(2'deoxyribofuranos-1'-yl) amino-2-bromoacrylamide (IIIa and IIIb respectively) were isolated as products in the photoreaction of III with ethylamine; the alpha anomer was produced in a dark reaction from the beta anomer. The identity of these anomers was established by comparison of their proton NMR spectra with those of the four corresponding alpha and beta furanosyl and pyranosyl isomeric nucleosides of thymine, which are presented in the Appendix. A study was also made of the reaction of I with methylamine; a ring opened product analogous to Ia, viz. N-(N'-methylcarbamoyl)-3-amino-2 bromoacrylamide (IIa) was formed. A similar study with 5-bromo-1-methyluracil produced N-(N'-methylcarbamoyl)-3-methylamino-2-bromoacrylamide (IIc) as a product. Likewise, the reaction of 5-chlorouracil with ethylamine was studied and N-(N'-ethylcarbamoyl)-3-amino-2-chloroacrylamide (Ie), which is analogous in structure to Ia, was found to be produced. Structural identifications were made through use of UV spectroscopy, high resolution 1H-NMR spectroscopy, mass spectrometry and, in the case of Ia and IIa, 13C-NMR spectroscopy. In the BrUra and BrdUrd reaction systems, described above, dehalogenation reactions accounted for a major portion of the products. The yields of ring opened products, determined at pH 10, ranged from a high of 10.3% in the BrUra-ethylamine system to a low of 1.7% in the MeBrUra-methylamine system.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1881961 TI - Psoralen-photosensitized damage of rat peritoneal exudate cells. AB - Psoralen-sensitized photodamage (PUVA) of rat peritoneal exudate cells was investigated. Quartz-activated luminol-dependent chemiluminescence (ChL) was registered and the amount of trypan-positive cells was determined. Irradiation of peritoneal exudate cells in the presence of psoralen resulted in a dose-dependent monotonous inhibition of ChL. The reciprocity law of irradiation intensity and duration of irradiation was not valid for the observed inhibition of ChL: the inhibition increased with higher intensity. When psoralen previously photooxidized in ethanol (POP) was added to peritoneal exudate cell suspension, a double-phase response depending on psoralen irradiation dose was obtained: ChL activation was observed at low doses of UVA, ChL inhibition at high doses. Chemiluminescence inhibition correlated well with the increase in the number of trypan-positive cells. It may be supposed that the observed effects of PUVA or POP treatment are caused by cell cytoplasmic membrane damage. PMID- 1881962 TI - The effect of the antihistamine cimetidine on ultraviolet-radiation-induced tumorigenesis in the hairless mouse. AB - This experiment investigated the effect on ultraviolet (UV) radiation-induced tumorigenesis of feeding the histamine type 2 receptor antagonist, cimetidine, to Skh:HR mice. Cimetidine was fed to one group during a 70 day period of chronic UVR (5 days/week for 10 weeks), to a second group from the end of this period to the end of the experiment at 286 days and a third group was fed a control diet only throughout the experiment. Feeding mice cimetidine during the 70 day period of irradiation protected them against the later development of skin tumours. PMID- 1881963 TI - Enhanced growth and experimental metastasis of chemically induced tumor in ultraviolet irradiated syngeneic mice. AB - Recent studies have shown that ultraviolet (UV) irradiation induces a systemic effect which enhances subsequent tumor induction by benzo[a]pyrene in a manner which is dependent on the dose of benzo[a]pyrene. The present study was designed to test whether UV-B irradiation renders mice susceptible to subcutaneous or intravenous injection of a regressor tumor induced by benzo[a]pyrene. The sources of UV-B irradiation were banks of 6 Westinghouse FS-40 sunlamps, situated 20 cm above the mouse cages. Female BALB/cAnNHsd received five 30-min dorsal UV-B radiation treatments per week for 12 weeks, resulting in a total dose of approx. 6.4 x 10(5) J m-2. Two to seven days after termination of UV treatments, syngeneic regressor tumor cells (BP2) induced by benzo[a]pyrene were injected subcutaneously or intravenously into irradiated mice and unirradiated controls. By 38 days post subcutaneous implantation, 24/30 and 3/30 BP2 implants were detectable in the irradiated and unirradiated mice, respectively. Ultraviolet irradiated mice were also unable to reject lung colonies resulting from intravenous administration of BP2 cells, although they were rejected by unirradiated mice. The mean number of lung colonies per mouse was 16- to 35-fold greater in UV irradiated mice than in unirradiated controls, at 14 to 17 days post injection. Thus, UV irradiation rendered mice, with no known exposure to benzo[a]pyrene, susceptible to a subcutaneous or intravenous injection of a regressor tumor induced by benzo[a]pyrene. PMID- 1881964 TI - Expression of AP 3, 4 and 5 isophytochromes in etiolated oat seedlings (Avena sativa L.). AB - Type 1 phytochrome from etiolated oat seedlings was digested with V-8 protease. Microsequencing of a 13 kDa fragment yielded a sequence of 31 amino acids. The fragment starting with the alanine residue at position 427 of the entire phytochrome amino acid sequence revealed a heterogeneity (threonine, alanine and asparagine) at position 10. This demonstrates that the phytochrome type A genes AP3, 4 and 5 are expressed as proteins. PMID- 1881965 TI - Protective role of butylated hydroxytoluene and certain carotenoids in photocarcinogenesis. AB - Butylated hydroxytoluene (BHT) and certain carotenoid pigments have been found to inhibit photocarcinogenesis in animal models. In addition, BHT protects against UV-B-induced erythema and UV-B induction of ornithine decarboxylase. Studies on the photoprotective mechanism(s) of BHT suggested that changes in the physico chemical properties of the keratin of the stratum corneum layer of skin occurred, leading to increases in UV absorption of that tissue. These changes might be exerted via the anti-radical action of BHT that retards oxidation and prevents cross-linking of the keratin chains, resulting in a diminution of UV-B radiation reaching potential target sites. The carotenoids beta-carotene, canthaxanthin and phytoene also inhibit UV-B carcinogenesis. beta-Carotene and canthaxanthin are excellent quenchers of singlet oxygen, and all three pigments can quench free radicals. beta-Carotene and canthaxanthin have been shown to quench singlet oxygen/free radical reactions in the skin of porphyric mice, and these two pigments as well as phytoene have been found to quench excited species formed on irradiation of mouse skin by UV-B. PMID- 1881966 TI - Evidence for a dissociation between cardiovascular and behavioral reactivity in the spontaneously hypertensive rat. AB - Spontaneously hypertensive rats of the Okamoto strain (SHR) were compared with normotensive rats of the Wistar-Kyoto strain (WKY) on the acoustic startle response in rats prepared for simultaneous blood pressure recordings. Blood pressure was continuously recorded by means of an indwelling cannula in the caudal tail artery. The presentation of the startle stimulus caused a blood pressure response in both strains consisting of an initial increase in blood pressure followed by a decrease and after that a longer lasting, but less pronounced second increase in pressure. The startle-elicited increase in blood pressure was significantly elevated in SHRs and at the same time the acoustic startle response was depressed as compared to WKY rats. These data indicate a dissociation between cardiovascular and behavioral reactivity in the SHR. PMID- 1881967 TI - Effects of bilateral clamping of carotid arteries on hippocampal kindling in rats. AB - Moderate reduction of cerebral blood flow by bilateral clamping of carotid arteries (BCCA) in pentobarbital anaesthetized Wistar rats induces decreased PO2 and temperature values in vulnerable brain structures such as hippocampus and frontal cortex during the acute phase of clamping. Up to two weeks chronic increased GABA contents in hippocampus, substantia nigra and frontal cortex could be observed. During this time the development of hippocampal kindling was difficult. These results demonstrated an acute and chronic influence of GABA on most vulnerable brain structures which, however, do not lead to ischemic impacts as histological analyses demonstrate. PMID- 1881968 TI - Hormone-dependent aggression in the female rat: testosterone plus estradiol implants prevent the decline in aggression following ovariectomy. AB - Female rats were individually housed with a sterile male for the duration of the experiment. Beginning 7 to 10 weeks after the start of cohabitation, each female was tested for aggression toward an unfamiliar female at weekly intervals for 3 weeks. Females that displayed consistent and substantial aggression were given one of the following treatments: ovariectomy followed by both testosterone and estradiol implants, ovariectomy followed by 2 empty implants, or sham ovariectomy followed by 2 empty implants. The implants were subcutaneously placed hormone filled Silastic capsules. They were expected to produce a serum testosterone concentration of 0.5 ng/ml and an estradiol concentration of 15 pg/ml. Postoperatively, the aggression of each female continued to be assessed on a weekly basis for 3 weeks. Ovariectomized females with hormone implants displayed a level of aggression postoperatively similar to that of sham-ovariectomized females and significantly greater than that of ovariectomized females with empty implants. These results, together with others, suggest that estradiol and testosterone act together to form the hormonal foundation of hormone-dependent aggression by females cohabiting with a sterile male. PMID- 1881969 TI - Intravenous administration of progesterone and the onset of receptivity in female hamsters. AB - Progesterone-facilitated receptivity is believed to be a genomically mediated event. However, in contrast to estrogen, progesterone's effects occur rapidly. This experiment was designed to examine the temporal onset of receptivity in hamsters following intravenous (IV) administration of progesterone. Ovariectomized female hamsters were tested for their responsiveness to 10 micrograms estradiol benzoate (EB) plus 0, 50, or 200 micrograms progesterone, administered subcutaneously (SC). The hamsters were tested for sexual receptivity at 0.5, 1, 1.5, 2, 3 and 4 h. Three days later they were fitted with jugular catheters. Two days after catheter implantation they received 10 micrograms EB SC; 48 h later they were tested for receptivity and then received an IV injection of 0, 50, or 200 micrograms progesterone in 0.2 ml propylene glycol. Following the IV P injection the animals were again tested at 0.5, 1, 1.5, 2, 3 and 4 h. Progesterone administration (either SC or IV) resulted in an increase in total lordosis duration (TLD) over time. TLD had significantly increased from the pre progesterone levels by 2 h after 50 micrograms progesterone IV. In contrast, 50 micrograms progesterone SC did not cause an increase in TLD until 3 h postinjection. Moreover, in comparison to SC administration, the effects of IV progesterone were short-lived; TLD was significantly decreased by 4 h after injection. Following 200 micrograms progesterone, the latency to respond was shorter than with 50 micrograms progesterone (1.5 vs. 2 h). There was no difference in the onset of receptivity as a function of route of administration at the 200 micrograms dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1881970 TI - Plasma catecholamine responses during a personalized physical stress as a dynamic characterization of essential hypertension. AB - High performance liquid chromatography (HPLC) with electrochemical detection proves to be a reliable method for determination of plasma catecholamines (CA) to assess the possible role of the sympathetic nervous system (SNS) in essential hypertension (EH). The present investigation in a group of 15 normotensive (N) and 13 stable EH patients, homogeneous for age and duration of hypertension, was carried out without treatment in the supine position, up-right position and during a personalized bicycle exercise. Mean blood pressure, mean heart rate, plasma renin activity and plasma aldosterone were also evaluated at the various exertion phases. Norepinephrine (NE) and epinephrine (E) showed a progressive increase in N and in EH patients, reaching the highest values at maximum effort. However, EH patients showed higher E plasma levels than N before maximum effort. Dopamine (DA) reached the highest values in N at maximum effort and in EH patients at recovery time. These findings allow us to foresee the possibility of a better characterization of the SNS role in EH. PMID- 1881971 TI - Effects of hydrational state on ingestion in infant rats: is dehydration the only ingestive stimulus? AB - The physiological stimulus for deprivation-enhanced ingestion was studied in developing rats. During an overnight deprivation period, continuous gastric infusions of isotonic saline or milk were made to 6- and 15-day-old rat pups in order to preferentially maintain hydrational or hydrational and nutritional status, respectively. Pups' ingestion was then studied in oral-infusion tests. In 6-day-old pups that received either milk or saline infusions, ingestion was depressed relative to intake in pups that were simply deprived. But in 15-day-old pups, only milk infusions reduced intake. These findings suggest that the increased ingestion stimulated by deprivation in pups less than a week of age results primarily from dehydration, and thus that nutrient-related feeding does not emerge until later in development. PMID- 1881972 TI - An assessment of handedness in mice. AB - Mice from a pool of inbred strains (384 males and 329 females) were tested for handedness according to Collins' protocol in order to assess the reliability of this measurement. As previously reported by Collins these data revealed that a) approximately half of the mice were right-handed and half left-handed, b) most of the mice were strongly lateralized and c) females were more lateralized than males. The study of the psychometric characteristics of the test suggested that this measurement of behavioral asymmetry is both stable and observer independent. The test of paw preference also appeared to measure preexisting lateralization and was not a function of training during the test. PMID- 1881973 TI - Stimulation in prefrontal cortex inhibits conditioned increase in blood pressure and avoidance bar pressing in rats. AB - In our previous work, it was established that stimulation in a precisely defined area of the prefrontal cortex and in nucleus accumbens inhibits motor and cardiovascular components of the defence reaction elicited by stimulation in hypothalamus or amygdala, but it did not inhibit operant appetitive bar pressing. In the present investigations it was shown that electrical stimulation in the same area of prefrontal cortex and in the nucleus accumbens inhibited blood pressure increases elicited by a conditioned sound. In another set of experiments it was also shown that it inhibited bar pressing developed with Sidman's schedule. It is therefore concluded that inhibition originating in the described region of the prefrontal cortex is specifically addressed to motor and cardiovascular components motivated by fear or aggression. PMID- 1881974 TI - Stereotypic behavior, adrenocortical function, and open field behavior of individually confined gestating sows. AB - The adrenocortical response and open field behavior of a random sample of 37 individually confined gestating sows in different parities were tested around day 85 of pregnancy. The sows were classified as stereotyped [S] and nonstereotyped [N] based on 8-h individual behavioral observations during daytime. Behavioral analysis from time-lapse video recordings included percentage of time spent standing and sitting, as well as the duration spent performing elements of stereotyped actions. Blood samples were drawn for cortisol analysis by suborbital sinus puncture before and after adrenocortical stimulation with 200 IU ACTH. Locomotor activity in an open field, isolated visually and auditorily from other sows, was also studied. Seventeen sows exhibited stereotyped behavior for 54.9 +/ 4.8% of the 8-h observation period during daytime. The total time the sows spent standing and sitting was positively correlated with age and was significantly higher for [S] sows than for [N] sows. Sows in the [S] group exhibited a higher adrenocortical response to ACTH stimulation than [N] sows. Mean locomotor scores in the open field were higher for [S] than for [N] sows but these did not correlate with the physical activity and adrenocortical function in the home crate. Our results provide no evidence that the performance of stereotypies constitutes a mechanism that helps sows to cope in an environment of low complexity. PMID- 1881975 TI - Capsaicin affects aggressive behavior, but not hot plate responding, of adult male mice. AB - Adult male mice of albino Swiss-derived CD-1 strain were used to assess the effects of capsaicin (a powerful agent that produces a marked depletion of the undecapeptide substance P) on both intraspecific aggressive behavior (induced by 8 weeks of individual housing) and pain sensitivity. Capsaicin was given SC, 48 h before behavioral testing. Aggressive behavior, scored during a 5-min session under red light, was significantly enhanced by capsaicin treatment (50 or 100 microliters of a 7.5 mg/ml solution). In fact, Total Aggressive Episodes, Attacks, and Upright Offensive Posture were significantly higher in the two capsaicin-treated groups, while Latency to the first Attack was decreased, when compared to both vehicle or unhandled controls. A concomitant decrease in Submissive Postures and Flee was also evident in capsaicin mice. Hot plate testing (55 +/- 0.1 degrees C, cutoff time 30 s), carried out on nonisolated mice, did not reveal any difference among the two capsaicin groups (same doses) and vehicle or unhandled controls. PMID- 1881976 TI - Lasting effects of early chronic caffeine feeding on rats' behavior and brain in later life. AB - Pregnant dams were fed a 20% protein diet with caffeine (2 mg/100 g b.wt.), starting on day 9 of gestation. At birth, each dam with 8 assigned pups was fed this diet until weaning, day 22. On day 22, female rats were caged and fed this diet until day 93. Starting on day 93, the caffeine-supplemented diet was replaced with a caffeine-free, 20% protein diet until day 388. Starting on day 31, each animal was placed in a photoactivity cage, and locomotive activity was measured until day 375. On day 388, the animals were killed, and their brains were removed and divided into 7 regions. The weight, DNA, protein and zinc contents, and alkaline phosphatase activity of each region were determined. Locomotive activity of the caffeine-fed group was higher than in the noncaffeine control group. Accumulative activity scores showed 3 subgroups (high, medium, and low) in both groups at day 93. The medium activity subgroup in the caffeine group was greater than the controls from day 72 to day 93. These differences reappeared 5 weeks after cessation of caffeine supplementation and continued until day 375. The differences in activity were minimum in the high and low subgroups. Chronic caffeine intake in early life permanently affected the medium activity subgroup. Furthermore, various regions of the brain were biochemically altered in spite of the feeding of a noncaffeine diet for almost 300 days after caffeine. PMID- 1881977 TI - Magnitude estimation of adaptation to salt using a flow chamber for stimulus delivery. AB - Adaptation course to NaCl was estimated using a flow chamber for stimulus delivery and changes in the perceived taste magnitude as the criterion. The adapting stimulus of different durations was applied to one side of the tongue. Magnitude estimates were made by comparing the intensity of taste at the end of each adaptation time with the perceived intensity of the same stimulus applied briefly to the unadapted side of the tongue. The course of adaptation followed a negatively accelerated decreasing function. The relationship between taste magnitude and the duration of the adapting stimulus can be approximated by a logarithmic equation and, somewhat less accurately, also by an exponential equation, which can be related to the Beidler theory of taste stimulation. Some advantages of the closed flow technique and comparison of taste magnitudes on the adapted and unadapted sides of the tongue are discussed. PMID- 1881978 TI - Further analysis of the short-term inhibition of food intake in humans by the dipeptide L-aspartyl-L-phenylalanine methyl ester (aspartame). AB - It was reported previously that the dipeptide sweetener aspartame suppresses food intake in humans by a postingestive action. The present study examined the hypothesis that this is due to an effect of phenylalanine, one of the primary breakdown products of aspartame (phenylalanine is a potent releaser of the so called satiety hormone cholecystokinin, CCK). Capsulated aspartame (400 mg) administered to human volunteers reduced food intake by 15% (253 kcal) in a lunchtime test meal begun 1 hour later. However, neither phenylalanine (200 mg) nor the other constituent amino acid of aspartame, aspartic acid (200 mg), altered intake compared with placebo. Despite the large effect on food intake there were no treatment differences in pre- or postmeal ratings of motivation to eat. This suggests that aspartame may act to intensify the satiating effects of ingested food. Although high doses of phenylalanine reduce food intake, an individual action of phenylalanine cannot account for the potent anorexic effect of aspartame. In discussing alternative mechanisms it is noted that the amino acid sequence of aspartame (Asp-Phe) is the same as the C-terminal dipeptide of CCK. A direct action of aspartame at CCK receptors appears to be unlikely; however, aspartame might act as CCK releaser. Further studies are required to elucidate the mechanism of aspartame's anorexic action and perhaps to evaluate its therapeutic potential as an antiobesity agent. PMID- 1881979 TI - Importance of progesterone and estrogen priming for the induction of maternal behavior by vaginocervical stimulation in sheep: effects of maternal experience. AB - The effects of treating ovariectomised nulliparous and multiparous ewes with progesterone and estrogen on maternal behavior with or without vagino-cervical stimulation were investigated. Following 48 h of estrogen treatment there was neither evidence for stimulation of maternal behavior, nor a reduction in aggressive behavior, towards lambs by either multiparous or nulliparous ewes compared with control treatment (injections of the oil vehicle). Following 5 min of mechanical vaginocervical stimulation, the multiparous estrogen-treated ewes showed both positive maternal responses (low pitch bleats, licking, sniffing and approaching the lamb) and a reduction in aggression (butts) and negative behavior (withdrawal from the lamb) towards the lambs, whereas the nulliparous ewes showed only a reduction in aggression and negative behavior. Neither group showed positive maternal responses following vaginocervical stimulation without steroid priming. When the ewes received two weeks of progesterone priming prior to estrogen treatment, both multiparous and nulliparous ewes showed reduced aggression towards, and withdrawal from, the lambs compared to the control condition, but no positive maternal responses apart from an increased sniffing of the lamb. After vaginocervical stimulation positive maternal responses showed by multiparous ewes were significantly potentiated compared to those shown following estrogen treatment alone. Nulliparous ewes remained unresponsive on positive maternal behaviors. These studies show that hormonal priming has little effect in inducing the onset of maternal behavior in multiparous or nulliparous sheep but is an essential prerequisite for vaginocervical stimulation to do so in multiparous animals. PMID- 1881980 TI - Indices of stress in rats: effects of sex, perinatal alcohol and artificial rearing. AB - Three groups of rats were normally reared by dams, artificially reared but not exposed to alcohol or artificially reared and exposed to 6.6 g/kg/day of ethanol condensed into 8 h of each 24-h period. Alcohol exposure was given from postnatal day 4 through 9 and artificial rearing was conducted from postnatal day 4 to 12. In adulthood, approximately half of the rats were fitted with a chronic jugular catheter and were exposed to swim stress for 1 min in 21 degrees C water. Alcohol exposure augmented the corticosteroid stress response to the swim stress in female rats but not in male rats. The other half of the animals were tested for acquisition and extinction of a conditioned emotional response (CER). While alcohol exposure had no effects on the CER, extinction of CER was greatly accelerated by artificial rearing alone in female rats but not in male rats. Taken together, these findings suggest that some aspects of the stress response in female rats are more vulnerable to insults during the early postnatal period than those in male rats and that the insult-induced alterations can affect hormonal and behavioral measures differentially. PMID- 1881981 TI - Capsaicin desensitization and recovery on the human tongue. AB - The desensitization resulting from application of 10 or 100 ppm capsaicin was investigated, using daily testing of a capsaicin series (1-1000 ppm, in log steps). The series showed a significant decrement in perceived burn following desensitization with either concentration. Perceived burn of 100 and 1000 ppm did not recover from 100 ppm desensitization in six days, and perceived burn of 1 1000 ppm did not recover from 100 ppm desensitization in six days. When single capsaicin concentrations, rather than the series, were tested at one, two, four, or six days after desensitization, 10 ppm recovered from 10 ppm desensitization in one or two days, and 100 ppm recovered from 100 ppm desensitization between two and four days. This suggests that daily testing with the capsaicin series delayed recovery from desensitization. Nontasters of 6-n-propylthiouracil rated capsaicin burn lower than did tasters. The application method of rolling capsaicin onto the tongue with a swab was found to transiently inhibit burn. Implications for ingesting capsaicin products are discussed. PMID- 1881982 TI - Effects of nucleus basolateralis amygdalae neurotoxic lesions on aversive conditioning in the rat. AB - After bilateral stereotaxic administration of ibotenic acid on the n. basolateralis amygdalae, male adult rats were tested in the light-dark box apparatus to measure the time-course of the acquisition and retention of passive and active avoidance responses. The results show that after the lesions both passive avoidance and active avoidance acquisition were impaired. Passive avoidance responses were retained quite well, while active avoidance responses disappeared quickly. Conditioned freezing was almost completely absent. Thus it appears that the n. basolateralis plays a facilitatory role in all the conditioned responses which were investigated. PMID- 1881983 TI - Cardiovascular, neuropeptide Y, and adrenergic responses in stress are sexually differentiated. AB - Cardiovascular and sympatho-adrenomedullary responsiveness at rest and during stress were studied in weight-matched, sexually mature male and female rats. At rest, although there were no sex differences in cardiovascular parameters, females had two-fold higher plasma levels of norepinephrine (NE) and epinephrine. Resting plasma levels of neuropeptide Y-immunoreactivity (NPY-ir, a putative sympathetic cotransmitter and a vasoconstrictor) were similar in both sexes. Stresses of handling and cold (4 degrees C) water exposure induced greater pressor and tachycardic responses in males than in females. Males but not females exhibited a protracted recovery from the stress-induced pressor responses and a 2 fold increase in plasma NPY-ir suggesting that NPY release is sexually differentiated. Only in males, low basal plasma NE and NPY-ir levels inversely correlated with greater cold-induced pressor responses. Furthermore, in areflexic pithed rats, pressor adrenergic and NPY responses were greater in males than in females suggesting the possibility of "down"-regulation of vascular adrenergic receptors in females (due to elevated circulating catecholamines) and "up" regulation of NPY and adrenergic receptors in males. PMID- 1881985 TI - Methamphetamine effects on rat circadian clock depend on actograph. AB - Methamphetamine effects on the rest-activity rhythm were examined in 12 blinded rats using two different actographs, an Animex and a running-wheel. D Methamphetamine was administered chronically by dissolving it in drinking water. During methamphetamine treatment, the rest-activity rhythm measured by an Animex showed a clear sign of relative coordination in addition to the general enhancement of activity level. Analyses of pre- and posttreatment activity rhythms revealed that neither the phase nor the period was affected by methamphetamine treatment. On the other hand, the circadian period was lengthened by methamphetamine treatment when locomotor activity was measured by a running wheel. These results confirmed our previous findings that the chronic treatment of methamphetamine modified the expression of the circadian rhythms but did not affect the underlying oscillation when measured by an Animex, and further indicated that methamphetamine could affect the underlying oscillation when rats had free access to a running-wheel. It is concluded that the effects of methamphetamine on the circadian clock depend on actograph. PMID- 1881984 TI - Motor activity correlates negatively with free-running period, while positively with serotonin contents in SCN in free-running rats. AB - Free-running period of blinded rats kept in a cage with a running wheel varied markedly, while it varied little in rats kept in a cage without a running wheel. The mean free-running period of the former group is significantly shorter than that of the latter. In the former, the free-running period correlated negatively with motor activity, indicating that activity affects the free-running period. In both groups, essentially similar diurnal patterns of biogenic amines and their metabolites were observed in various discrete areas in the brain examined. However, there was a significant difference between the two groups in several areas. In the SCN, 5-HT content correlated positively with motor activity, consequently correlated negatively to the free-running period at 3 out of 4 sampling times over 24 h but no such correlation was observed in other monoamines and their metabolites examined. These facts suggest that 5-HT may be associated with modification of the free-running period. PMID- 1881986 TI - Inhibition of infanticide in male Swiss mice: behavioral polymorphism in response to multiple mediating factors. AB - The socio-sexual factors mediating the inhibition of pup-killing in previously infanticidal Swiss Webster male mice (Mus domesticus) were examined. As reported in other studies, postmating co-habitation (i.e., physical contact) with a female during pregnancy suppress pup-killing but the present experiments also showed that several factors are implicated in this phenomenon, namely: 1) Postcopulatory sensory contact (i.e., behind a wire-mesh partition) with the pregnant mate was sufficient to inhibit infanticide virtually in all the subjects. Copulation seems to function as a "primer," but cues, most likely of an olfactory nature, emitted by pregnant mate induce paternal behavior in the stud male. In fact, either copulation followed by sensory contact with a nonpregnant mate (abortion was induced) or sensory contact without copulation with a pregnant female did not suppress pup-killing in the majority of cases. 2) Mating, per se, is capable of inhibiting infanticide in a minority of males. 3) Physical contact with a parturient female (impregnated by another male) at the time of pup delivery inhibited infanticide in approximately 40-50% of males. The data essentially show that, in a house mouse population, there is a behavioral polymorphism in response to the coexisting multiple mechanisms which mediate the inhibition of infanticide. PMID- 1881987 TI - Soft drinks with aspartame: effect on subjective hunger, food selection, and food intake of young adult males. AB - Ingestion of aspartame-sweetened beverages has been reported to increase subjective measures of appetite. This study examined the effects of familiar carbonated soft drinks sweetened with aspartame on subjective hunger, energy intake and macronutrient selection at a lunch-time meal. Subjects were 20 normal weight young adult males, classified as either restrained or nonrestrained eaters. Four treatments of carbonated beverages included 280 ml of mineral water, one can of a soft drink (280 ml) consumed in either 2 or 10 minutes, or two cans of a soft drink (560 ml) consumed in 10 minutes, administered at 11:00 a.m. Subjective hunger and food appeal were measured from 9:30 a.m. to 12:30 p.m., and food intake data were obtained from a buffet lunch given at 12:00 noon. There were no treatment effects on energy intake, macronutrient selection or food choice at the lunch-time meal, or food appeal, though restrained eaters consumed more than nonrestrained eaters in all four treatment conditions. Consumption of two soft drinks (560 ml, 320 mg aspartame) significantly reduced subjective hunger from 11:05 a.m. to 11:30 a.m. compared to one soft drink (280 ml, 160 mg aspartame) or 280 ml of mineral water. Thus ingestion of soft drinks containing aspartame did not increase short-term subjective hunger or food intake. PMID- 1881988 TI - The effects of pregnancy and lactation on dietary self-selection in the rat. AB - Total food intake and intake of discrete dietary components, carbohydrate, fats, and protein, throughout pregnancy and lactation were measured in the albino rat, with virginal rats acting as controls. The dietary components were isocaloric and presented in a self-selection situation. Although the reproductive subjects ate more carbohydrate, protein, and total food than controls during the lactation phase, their intake did not significantly exceed that of controls during pregnancy. In addition, reproductive but not virginal animals changed patterns of selection over the reproductive periods. They consumed more total food during gestation and lactation, and more carbohydrate and protein during lactation. PMID- 1881989 TI - Salivary testosterone measurements: collecting, storing, and mailing saliva samples. AB - Salivary testosterone measurements can be especially useful in field studies, but reliable ways of collecting and handling samples need to be established. Using cotton dental rolls to collect saliva leads to inflated testosterone scores. Sugarfree gum can be used satisfactorily to stimulate saliva among both male and female subjects. Leaving unpreserved saliva samples at room temperature for 2 weeks or mailing them unrefrigerated is satisfactory for male subjects but leads to inflated scores for female subjects. PMID- 1881990 TI - A water-maze discrimination learning deficit in the rat following lesion of the habenula. AB - Although the habenula occupies a potentially important link between forebrain and midbrain, lesion of the complex produces little effect in most standard behavioral paradigms. More recently, it has been shown that such lesions may impair the ability to initiate or switch responses appropriate to environmental contingencies but only under demanding conditions. Although such deficits have been described as response failures, they could equally well be attributed to restricted attentional mechanisms. The present study was designed to further substantiate a role for the habenula in acquisition of adaptive behavior under demanding conditions and to examine the possible contribution of attentional failure. The initial response preference to 'escape' onto platforms situated in two chambers at the distal end of a water tank was established for groups of lesioned and sham-operated rats. Rats were subsequently trained in discrete trials to escape by choosing the side of the nonpreferred chamber. During training the choice of escape chamber was cued by distracting black or white visual stimuli displayed on the tank sides and above the entrances to the chamber. These were moved over trials so as to be nonpredictive of the appropriate escape position. Lesioned animals were significantly impaired in the acquisition of this positional discrimination. Analysis of response times suggested that both lesion and control animals were attending to the irrelevant visual cue. The results confirm a behavioral inflexibility following lesion of the habenula and suggest that this deficit cannot be explained simply in terms of a failure to attend to environmental cues. The lesion deficit also could not be attributed to a response perseveration. PMID- 1881991 TI - Previous experience facilitates preservation of spatial memory in the senescent rat. AB - In an attempt to evaluate whether previous training antagonizes age-related memory deficits, aged rats with previous training experience were compared with aged and young naive rats in the Morris water maze test. The findings of our study indicate that experience seems to facilitate the preservation of the spatial reference memory for 12 months in the aged rat, whereas senescent naive animals showed the usual age-related memory deficits. However, experience seems task-specific since the same aged rats fail to acquire a new different task. PMID- 1881992 TI - A method for long-term and accurate measurement and recording of the blood glucose level in man. AB - We describe a technique of continuous and long-term withdrawal of venous blood which permits a continuous measurement and recording of the blood glucose level. The preparation and setting up of a special double lumen catheter are detailed. This technique provides very accurate blood glucose time course determination and requires the withdrawal of small amounts of blood. PMID- 1881993 TI - Effect of zolpidem on sleep and sleep EEG spectra in healthy young men. AB - A single 10 mg dose of zolpidem, an imidazopyridine hypnotic, was administered to young, healthy male volunteers prior to bedtime. The drug reduced REM sleep but did not significantly affect other sleep stages and subjective sleep parameters. All-night spectral analysis of the EEG revealed that power density in nonREM sleep was reduced in the low-frequency range (1.25-2.5 Hz; 5.25-10.0 Hz) and increased in the spindle frequency range (12.25-13.0 Hz). Significant changes in the EEG spectrum were present in the first 4 h of sleep. The pattern of the spectral changes was similar to those induced by other hypnotics that bind to the GABAA/benzodiazepine receptor complex. There were no residual effects of zolpidem on psychomotor performance in the morning, on the self-rated state in the morning and at noon, and on sleep and EEG parameters in the subsequent drug-free night. PMID- 1881994 TI - Comparative pharmacokinetics of alprazolam and lorazepam in humans and in African Green Monkeys. AB - The comparative pharmacokinetics of alprazolam and lorazepam were evaluated in African Green Monkeys and in healthy male human volunteers. Six monkeys received a single 250 micrograms/kg oral dose of alprazolam and of lorazepam on two separate occasions. Mean kinetic values for the two drugs, respectively, were: elimination half-life, 5.7 and 1.7 h; oral clearance, 5.5 and 40.2 ml/min/kg. Healthy male volunteers (n = 22) received a single 1 mg oral dose of alprazolam; another group (n = 24) received a single 2 mg oral dose of lorazepam. Mean values of elimination half-life in humans (11.5 and 12.4 h, for alprazolam and lorazepam, respectively) were substantially longer than corresponding values in the primate animal model, and human values of clearance (0.85 and 1.40 ml/min/kg) likewise were much lower. However, in humans, kinetic differences between the two drugs were much smaller than in the primate animals. Thus comparative studies of the behavioral effects of these two drugs in African Green Monkeys should utilize relative dosages that reflect the pharmacokinetic properties of the drugs in that species. Use of dosage ratios analogous to those used in humans may lead to results that cannot be extrapolated to humans. PMID- 1881996 TI - Separate and combined effects of the social drugs on psychomotor performance. AB - Ten female subjects (five smokers and five non-smokers) performed a choice reaction time task (CRT), a compensatory tracking task (CTT), a short-term memory task (STM) and were tested for their critical flicker fusion threshold (CFF) at set points over 4 h after the administration of each possible combination of nicotine (2 mg gum or placebo), caffeine (250 mg capsule or placebo) and alcohol (30 g or placebo). Memory and motor function were shown to be facilitated by nicotine or caffeine, and the debilitating effects of alcohol were frequently antagonised by either drug. In spite of the differences in their neuropharmacological actions, combinations of nicotine, caffeine and alcohol may be compared through their effects on common information processing mechanisms involved in psychomotor performance. PMID- 1881995 TI - Chronic treatment with chlorpromazine, thioridazine or haloperidol increases striatal enkephalins and their release from rat brain. AB - The aim of this paper is to study the effect of 1, 2 or 3 months' administration of chlorpromazine (CPZ), thioridazine (TDZ) (2 or 6 mg/kg) or haloperidol (HAL) (0.25 or 1 mg/kg) IP on the level of leu- and met-enkephalin (ENK) in striatum. A dose- and time-dependent increase of striatal ENK level was observed after chronic administration of the neuroleptics (NL), but 8 days after withdrawal of chronically administered NL striatal ENK was decreased. Apomorphine pretreatment significantly attenuated the elevation in ENK produced by chronic injections of NL. In perfusion fluid obtained from the lateral ventricle of animals treated 1 month with HAL a dose-dependent increase of ENK levels was observed, which was augmented by potassium ions. It is concluded that: 1) Chronic administration of neuroleptic drugs that block dopamine receptors increases the level and the release of striatal enkephalins; 2) The results support the hypothesis that activation of dopaminergic neurons tonically inhibits the synthesis of enkephalins in the striatum. PMID- 1881997 TI - Effects of carbamazepine on acute responses to smoked cocaine-base in human cocaine users. AB - A double-blind, placebo-controlled cross-over study was conducted to determine the effects of carbamazepine on the acute physiological and subjective responses to a single dose of smoked cocaine-base. Male cocaine users (N = 6) were given 400 mg carbamazepine or placebo, each for a period of 5 days. At the end of the 5 day period, a 40 mg dose of smoked cocaine was administered. The results showed a significantly higher heart rate, diastolic blood pressure elevation, and blood pressure-heart rate product under the carbamazepine compared to the placebo condition. There were no effects of carbamazepine on the subjective responses from cocaine. The increase in cardiovascular functions indicates a need to be cautious in the use of carbamazepine in the treatment of cocaine abusers. PMID- 1881999 TI - Response disinhibition on a delayed matching to position task induced by amphetamine, nicotine and age. PMID- 1881998 TI - Time-, schedule-, and reinforcer-dependent effects of pimozide and amphetamine. AB - Rats performed on two multiple random-interval schedules, in which sequences of ascending or descending reinforcement densities were balanced between the schedules and between the two halves of the session. Using a standard reinforcer (10% sucrose pellets), pimozide decreased response rates, while amphetamine increased responding. The effects of both drugs were schedule dependent: larger changes were evident in low response rate, reinforcement-lean components than in high response rate, reinforcement-rich components. Both effects were also time dependent, increasing over the course of the session; this casts serious doubt on the applicability of Herrnstein's matching law for studying agents acting on brain dopamine. Increasing the period of food deprivation increased response rates, while withdrawing food deprivation decreased responding. These effects were also schedule dependent, but were time dependent. Substituting 95% sucrose pellets for standard 10% sucrose pellets caused an immediate and sustained decrease in responding, and up to 10% of earned reinforcement was not consumed. Pimozide increased response rates within reinforcement-lean components and reinstated the complete consumption of earned reward typical of standard reinforcement. These apparently paradoxical effects may be consistent with a decrease in the rewarding properties of sucrose pellets. Despite low response rates, amphetamine did not affect responding maintained by 95% sucrose pellets but did further reduce the consumption of earned reward. These results call into question the generality of the rate-dependency principle in the action of psychomotor stimulants. PMID- 1882000 TI - Sensitization to systemic amphetamine produces an enhanced locomotor response to a subsequent intra-accumbens amphetamine challenge in rats. AB - Repeated amphetamine (AMPH) administration into the nucleus accumbens does not enhance (sensitize) the locomotor activity produced by a subsequent systemic AMPH challenge. We report here, however, that pretreatment with systemic injections of AMPH does produce a significant enhancement in the locomotor stimulant effects produced by intra-accumbens AMPH given 21 days after the last pretreatment injection of AMPH. These data support the hypothesis that neural adaptations in dopamine (DA) terminal fields are sufficient for the expression of AMPH sensitization, although an action on DA cell bodies may be required for the induction of AMPH sensitization. PMID- 1882001 TI - Functional tolerance to the hypothermic effect of phenobarbital in rats. AB - Phenobarbital elicits a hypothermic effect in rats. To determine if functional tolerance develops to this effect on temperature, rats were treated twice daily with IP injections of sodium phenobarbital (PheB) or saline. The PheB doses were increased over 21 days and then were held constant for another 23 days. On the next day (day 45) animals from both groups were given 80, 110 or 160 mg/kg PheB IP and the decrease in rectal temperature after 2 h was determined. Animals were decapitated after the temperature measurement and brain PheB levels were determined. A 1.51-fold shift in the relationship between brain level and response was found for the group given chronic PheB. These results show functional tolerance occurs to the hypothermic effect of PheB. This experiment was done in animals that were on a restricted food regimen. Rats given chronic PheB lost more weight than the group given chronic saline unless extra food was provided. We found that this occurred because the rats given chronic PheB lost more food through the wire cage floor than rats given chronic saline. PMID- 1882003 TI - Beta-endorphin-induced locomotor stimulation and reinforcement are associated with an increase in dopamine release in the nucleus accumbens. AB - In vivo microdialysis was used to compare the effects of beta-endorphin upon dopamine (DA) release in the nucleus accumbens (NAC) of anesthetized versus freely moving rats, and to examine the role of the mesolimbic DA system in mediating both the motoric and secondary reinforcing effects of this peptide. Microdialysis probes were inserted into the NAC and perfusates were analyzed for DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), using a reversed phase HPLC system with electrochemical detection for separation and quantification. Intracerebroventricular (ICV) administration of beta-endorphin (2.5 and 5.0 micrograms) increased DA release and metabolites in both freely moving and anesthetized rats. This effect was of greater magnitude and duration in freely moving rats and was accompanied by stimulation of locomotor activity. The 5 micrograms dose also functioned as a secondary reinforcer in a conditioned place preference paradigm. A higher dose of beta endorphin (7.5 micrograms) stimulated DA release and metabolites in anesthetized rats but failed to affect these parameters in freely moving rats. At this dose, catalepsy and a loss of the reinforcing effects of this peptide were observed. These data demonstrate marked differences in the effects of beta-endorphin upon DA release in the awake versus anesthetized rat. Further, the finding that the reinforcing and locomotor stimulating effects of beta-endorphin only occur at those doses which stimulate DA release suggest that this action is critical for the expression of both behavioral effects. PMID- 1882002 TI - Standardization of the rat paw formalin test for the evaluation of analgesics. AB - Administration of 5% formalin into the rat or guinea pig hind paw evokes two spontaneous responses: flinching/shaking and licking/biting of the injected paw. The temporal and behavioral characteristics of these objective endpoints are described. Additionally, several practical suggestions aimed at standardizing this test for the evaluation of analgesics are presented. The early/acute and late/tonic (0-10 and 20-35 min post-formalin, respectively) phases of flinching were used to quantitate antinociception in the rat. PD 117302, the kappa selective agonist, was three times more potent than morphine against tonic flinching after SC administration. Formalin may therefore be a noxious stimulus of choice in the evaluation of kappa agonists. Morphine was only twice as potent against tonic flinching as against acute flinching or the tail-dip reflex to water (50 degrees C). In contrast, PD 117302 was 27 times less potent on early phase and was inactive in the tail-dip test. Thus, while morphine is essentially equipotent across tests, PD 117302 shows a spectrum of activity with impressive potency and efficacy being obtained against tonic pain. Kappa receptors may therefore be prominently involved in tonic pain states. Aspirin given orally was not consistently antinociceptive in either phase of the formalin test. Spinal transection completely abolished late phase responding but only partly attenuated flinching in the early phase. This suggests that the relative involvement of spinal (as opposed to supraspinal) processing of noxious inputs may, at least in part, be a function of stimulus intensity and underlie the differences in antinociceptive potency observed in this work. PMID- 1882005 TI - Diazepam withdrawal responses measured in the social interaction test of anxiety and their reversal by baclofen. AB - After 21 days of treatment with diazepam (0.5 or 2 mg/kg/day) rats were tolerant to the effects of diazepam to increase social interaction in the low light unfamiliar test condition of the social interaction test of anxiety. When they were tested 24 h after the last of 21 injections they showed significant decreases in social interaction, indicating an anxiogenic withdrawal response. However, the social interaction scores of rats tested 48 h after withdrawal from diazepam treatment were no longer different from those of the control group. The decreased social interaction, indicating increased anxiety, detected 24 h after withdrawal of diazepam (21 daily injections of 0.5 or 2 mg/kg), could be reversed by the usual daily diazepam dose (0.5 or 2 mg/kg, respectively) or by baclofen (0.5 or 1 mg/kg). Baclofen (2 mg/kg) was sedative in both control treated and diazepam-dependent rats, but was ineffective at reversing the decrease in social interaction seen after diazepam withdrawal. Possible sites of action mediating these effects of baclofen are discussed, and it is suggested that either post synaptic GABAB sites in the hippocampus are involved or that the reversal of the decreased social interaction detected on withdrawal of diazepam treatment is due to a baclofen-mediated inhibition of 5-HT release in the hippocampus. PMID- 1882004 TI - Reduction of oxotremorine-induced analgesia after chronic but not acute restraint stress. AB - The analgesic response (tail-flick latency) induced by the muscarinic cholinergic agonist oxotremorine was investigated in DBA/2 mice exposed to acute (a single 2 h session) and chronic (2 h once daily for 10 days) restraint stress. While a single exposure to stress did not influence the antinociceptive effects of the cholinergic agonist, chronic stress induced a clear-cut reduction of the oxotremorine-induced analgesia. The results show an involvement of cholinergic mechanisms in the adaptive modulation of nociception after chronic stressful events. PMID- 1882007 TI - Effect of buspirone on cigarette withdrawal symptoms and short-term abstinence rates in a smokers clinic. AB - This paper reports on a double blind trial of the effect of buspirone, 15 mg per day, on cigarette withdrawal symptoms and ability of smokers to maintain abstinence during treatment. A total of 61 smokers were randomly assigned to active or placebo conditions. They were maintained on their drug for 2 weeks prior to attempting abstinence and then for a further 4 weeks of abstinence. Subjects attended weekly group sessions of a psychological treatment programme. There was no evidence that the side effects in the active drug group were worse than those in the placebo group. Although there was no significant difference between active and placebo conditions on withdrawal symptoms, smokers in the active drug condition were more than twice as likely to maintain abstinence for the duration of the study than those in the placebo condition (47% versus 16%, chi square = 5.3, P less than 0.025). The results provide preliminary evidence for short-term efficacy of buspirone as an aid to smoking cessation at a low dose. They also provide evidence of a dissociation between withdrawal symptoms and successful abstinence. PMID- 1882006 TI - EEG and ERP response to chronic ethanol exposure in rats. AB - Chronic ethanol exposure has been described in humans to produce a series of long and short term electrophysiological consequences. Interpretation of the electrophysiological findings in human subjects, however, is made difficult due to concomitant factors, such as nutritional status, premorbid functioning and differences in genetic susceptibility to the effects of ethanol. In the present study, electroencephalograms (EEGs) and auditory event related potentials (ERPs) were utilized to explore the short and longer term effects of chronic ethanol exposure in rats. Rats were continuously exposed to ethanol vapors for a period for 1 month. This treatment produced a mean blood ethanol level of 178 +/- 13.86 mg%. EEGs and ERPs were subsequently collected at 10 min, 24 h, and 2 weeks following termination of ethanol exposure. Significant changes in the EEGs and ERPs of these rats could be demonstrated. EEG amplitude increases, as quantified by spectral analysis, were most prominent at the 24 h time period, perhaps reflecting a state of "rebound excitability". EEG responses were normalized in ethanol-treated rats by 2 weeks post-withdrawal. In contrast, reductions in the N1 and P2 amplitudes of the rat ERPs were prominent after chronic ethanol exposure and following 2 weeks withdrawal, suggesting that ethanol may produce some longer term effects on response to ERP stimuli. Taken together, these studies suggest that ethanol may produce differential effects on EEG and ERPs and that this model may provide a useful substrate for the evaluation of the mechanisms underlying the effects of chronic ethanol exposure. PMID- 1882008 TI - Meta-analysis: a review. PMID- 1882009 TI - Cluster analyses of cardiovascular responsivity to three laboratory stressors. AB - Seventy-three young normotensive male subjects were tested with an experimental protocol that included a reaction time, a mental arithmetic, and a cold pressor task. Physiological variables that were recorded included heart rate, stroke volume, pre-ejection period, blood pressure, total peripheral resistance, and respiratory sinus arrhythmia. In order to identify subgroups of subjects who differed in their pattern of autonomic responses to the tasks, the physiological change scores from baseline to the tasks for each subject were entered into a cluster analysis for each task. Ward's method was used as the clustering algorithm. The cluster analyses identified four clusters for the reaction time and mental arithmetic tasks, and five clusters for the cold pressor task. Although there was a wide range of patterns exhibited by cluster subgroups, most subjects who were reactive to the tasks showed response patterns that were qualitatively similar to the pattern of overall mean response by all subjects, albeit varying considerably in terms of quantitative response. Little evidence was generated for the consistency of extreme beta-adrenergic response from one task to another, although significant consistency was noted when milder beta responders were included in the comparisons. Some consistency of alpha-adrenergic response noted across tasks, as well as significant consistency of being relatively nonreactive to the tasks. PMID- 1882010 TI - Social competence interview for assessing physiological reactivity in adolescents. AB - Difficulties in predicting "real life" physiological variation from responses to controlled stress tasks suggest the need for more ecologically valid laboratory challenges. The Social Competence Interview (SCI) measures physiological changes elicited by re-experiencing a life situation in which a valued striving was unexpectedly hindered. The 14-minute interview yields data on subjects' goals, skills, problem-solving strategies, and social resources. We compared the SCI to video game (VG), mirror drawing (MD), and mental arithmetic (MA) in a racially balanced sample of 260 adolescents (age 14 to 15 years). Blood pressure changes during SCI exceeded those during the other tasks, and were unaffected by race or gender. Blood pressure responses to SCI correlated with responses to MA and MD but appeared to capture a unique domain of social reactivity. Test-retest correlations over 6 months in a random subsample of 27 subjects showed that blood pressure reactivity to SCI and other tasks was reproducible. Intrasubject analyses of responses to the different tasks disclosed subgroups of consistently high and consistently low responders who may be at higher or lower risk. The SCI is not threatening and was rated by subjects as less frustrating or demanding than MD or MA. Its demonstrated effectiveness when administered by several different interviewers suggests the SCI is a promising technique for large scale studies of younger populations. PMID- 1882011 TI - Relationship of personality characteristics to glucose regulation in adults with diabetes. AB - Personality characteristics were assessed in 139 diabetic adults (insulin dependent diabetes mellitus = 84, non-insulin-dependent diabetes mellitus = 55) to determine whether a relationship existed between glucose regulation and the measured psychological features. Cloninger's Tridimensional Personality Questionnaire (TPQ) was used to evaluate personality while glycated hemoglobin provided an estimate of recent glucose control. Mean glycated hemoglobin (gHb) for the sample was 11.4%. A significant difference (p = 0.03) in gHb levels was observed comparing subjects with extreme personality features (mean = 11.9%) with those subjects with average personality profiles (mean = 10.9%). Post hoc statistical testing identified opportunistic, alienated, and explosive temperaments as the personality features most often associated with poor glucose control. The TPQ appeared to be a particularly useful predictor of poorer glucose regulation in the subset of patients who were self-referred. PMID- 1882012 TI - Group size, cage shelf level, and emotionality in non-obese diabetic mice: impact on onset and incidence of IDDM. AB - We hypothesized that differential housing, shown to influence emotionality and health in infectious and neoplastic disease, would influence onset/incidence of diabetes in an autoimmune animal model of insulin-dependent diabetes mellitus (IDDM). Non-obese diabetic mice were assigned to same-sex groups of one, five, or eight animals/cage, counterbalanced across shelf level by sex and group. During weekly urine glucose testing, presence of behaviors indicating emotional arousal was recorded. Sex, group, and shelf level affected emotionality: males, animals housed alone, and those on the top of the rack exhibited higher emotionality. Emotionality and shelf level predicted IDDM in females only. Delayed onset of IDDM was associated with high emotionality and with being housed on the top of the rack. Group size had no significant effect on IDDM. Emotionality may be a mediating factor in animals genetically predisposed to develop IDDM. This variable and cage shelf level should be incorporated into the design of studies in which IDDM is the outcome. PMID- 1882013 TI - Hamsters with coronary vasospasm are at increased risk from stress. AB - Results of earlier experiments suggested that hamsters with inherited heart disease were at a higher risk of succumbing to stress during the vasospastic, lesion-forming period of their lives rather than later when the process of congestive heart failure had begun. To test this hypothesis, we stressed cardiomyopathic hamsters (CMH) whose ages differed by about 3 months; the younger of the two groups of stressed hamsters was in the vasospastic phase of the disease. The stressor was cold immobilization in which stressor intensity was manipulated using two durations of cold exposure. Log rank survival curves revealed no difference in mortality with the more intense stressor. However, significantly fewer of the older hamsters succumbed to the less intense stressor (46% as compared with 85% of the younger CMHs). Examination of the hearts in the experiment where mortality rate was the same for both groups revealed evidence of cardiac dilatation, indicative of heart failure, only in the older hamsters following stress. Since the younger hamsters did not show these changes and since they, but not the older animals, have coronary microvascular spasm and an increased susceptibility to stress, it would appear that the process of coronary vasospasm should be viewed as an independent and additional risk factor in determining the consequences of stress. Because of the effects of stress in the younger cardiomyopathic hamster, we believe that a neural link--which can be activated by stress--may be involved in the pathogenetic process of coronary vasospasm. PMID- 1882014 TI - Temperament and allergic symptoms. AB - Two independent studies of the first and second degree relatives of extremely shy versus sociable children revealed greater prevalence of hayfever and social anxiety among the relatives of the former group of children. These data, which are in accord with other research, imply a genetically mediated relation between social anxiety and selected atopic allergies. PMID- 1882015 TI - An AIDS bibliography for the general psychiatrist. PMID- 1882016 TI - Psychological factors affecting neurological conditions. Depression and stroke, multiple sclerosis, Parkinson's disease, and epilepsy. AB - As a contribution to the proposed revision of the DSM-III-R category "Psychological Factors Affecting Physical Condition" for DSM-IV, this article reviews the history of how the relationship of psychiatric illness to neurological illness has been understood with respect to depression. Since both psychiatric and neurological illness are aspects of brain functioning, any statement of the relationship of these categories entails certain epistemological assumptions, some of which have undergone considerable change and rapid evolution in the course of the last century. PMID- 1882017 TI - The consequences of maternal substance abuse for the child exposed in utero. AB - The marked increase in substance abuse in the United States represents a significant risk to the development of children exposed in utero to tobacco, alcohol, and illicit drugs. This paper reviews the current literature exploring the effects of the major substances of abuse on in utero and childhood development. PMID- 1882018 TI - Effects of uncomplicated acute myocardial infarction on biochemical parameters of stress and sexual function. AB - The blood levels of several "stress indicators" (prolactin [PRL], growth hormone [hGH], total catecholamines, and adenosine 3',5'-cyclic monophosphate [cAMP]) were measured in men during the first 2 weeks of uncomplicated acute myocardial infarction (AMI) and during a 3-month follow-up period. PRL levels were significantly elevated during the first day, and hGH was elevated during the week after the AMI. The levels returned to the control baseline values thereafter. The levels of the total catecholamines and cAMP in blood remained normal throughout the study period. Sexual function during the 3-month follow-up was measured in 29 patients, using a specially designed questionnaire. Impotence was found in five patients and decreased libido in four. No correlation was noted between PRL values, the other stress indicators, and sexual dysfunction. A trend toward increased incidence of sexual dysfunction was found among patients with recurrent AMI. PMID- 1882019 TI - Symptoms of depression in patients with type II diabetes mellitus. AB - Patients with type II diabetes mellitus were assessed for symptoms of depression using the Zung Self-Rated Depression Scale (Zung SDS) and the Beck Depression Inventory (BDI). The patients were classified according to the presence or absence of diabetic complications, and they were compared with a group of demographically matched, nonmedically ill control subjects. The patients with diabetic complications scored significantly higher on the depression inventories than did the patients without complications and the control subjects. Factor analysis of BDI responses revealed that cognitive symptoms of depression were prominent in the diabetic patients with complications. In this group, 74% of patients scored within the range of clinical depression on the BDI; 35% scored within the range of severe depression. Symptoms of sexual dysfunction were significantly correlated with symptoms of depression in diabetic women but not in diabetic men. The findings are discussed within the context of other research in the behavioral aspects of diabetes mellitus. PMID- 1882020 TI - Drug and alcohol abuse in patients with acute burn injuries. AB - We reviewed records of adult patients admitted to our burn unit who were reported to abuse drugs or alcohol from 1985 to 1988. The proportion of patients reported as abusing drugs increased significantly from 1987 to 1988, compared to previous years. However, there was no increase in the proportion of patients reported to abuse alcohol. Patients identified as abusing drugs had longer hospital stays, compared to patients who were not reported to abuse substances. Methamphetamine and cocaine were the drugs most often abused by patients who abused drugs or both drugs and alcohol. Mechanisms of burn injury in these patients included "accidental" burn injury related to acute intoxication, and self-injury due to psychosis or depression. PMID- 1882021 TI - Chronic pain patients and the nonorganic physical sign of nondermatomal sensory abnormalities (NDSA). AB - The nonorganic physical sign of nondermatomal sensory abnormalities (NDSA) is frequently found in chronic pain patients. The presence of NDSA qualifies the patient for a potential DSM-III diagnosis of conversion disorder. DSM-III (Axis I and II) diagnoses and personality styles were assigned to 283 mixed chronic pain patients. Discriminant analysis was used to identify diagnoses and personality styles significantly related to NDSA. The demographic variables of workers' compensation (WC) status, age, sex, and race were used as control variables. The discriminant function comprised all control variable, and psychiatric diagnoses accounted for only 22.1% of the variance. Age and WC status, i.e., the demographic variables, explained most of the variance (16.8%), with psychiatric diagnoses adding little (5.3%). The vast majority of the variance is unexplained, indicating the presence of "unexplained" factors for the presence of NDSA in chronic pain patients. PMID- 1882022 TI - A psychiatry outpatient consultation-liaison clinic. Experience at the Cleveland Clinic Foundation. AB - This report describes the patients seen during the first 3 months of operation of a psychiatry outpatient consultation-liaison (C-L) clinic. A total of 113 patients were seen. For 8% of the appointments made, patients did not show up; the cancellation rate was 3.8%. Depression, anxiety, stress, and somatic symptoms were the most common reasons for referral, while the most common diagnoses made were major depression, adjustment disorder, and panic disorder. Practitioners in the fields of internal medicine, primary care, and psychology made the majority of the referrals. Patient satisfaction as expressed in a written survey was high. The results showed that an outpatient C-L clinic can be an effective way to access and treat medicine, surgery, and psychology outpatients in a big hospital setting. PMID- 1882023 TI - Hypoalbuminemia in delirium. AB - The charts of 100 delirious patients seen by a psychiatric consultation service were reviewed. The most common chronic medical problems included diabetes and cardiovascular disease, while infections and trauma were the most common acute problems. The most frequent laboratory abnormality was hypoalbuminemia, appearing in 66% of those tested. Hypoalbuminemic patients were more likely to have a combination of medical problems, long hospital stays, and increased mortality, while patients with normal albumin were more likely to have drug toxicities and short hospital stays. While hypoalbuminemia develops because of many physiological processes, the data suggest that more attention should be paid to nutrition and serum transport capability in medical patients. PMID- 1882025 TI - Psychological and behavioral benefits of a stress/type A behavior reduction program for healthy middle-aged army officers. AB - Twenty army officers who participated in a stress/type A behavior reduction program and a comparison group of 17 officer nonparticipants volunteered to undergo a battery of psychological and behavioral tests before and after the program. Following the program, participants displayed a significantly greater reduction in average daily caloric intake and levels of perceived stress, anxiety, hostility, depression, psychological distress, and type A behavior as compared to the officers who did not participate in it. Given the fact that most of these psychological and behavioral factors have been found in previous studies to be related to an increased risk for coronary artery disease, it seems that the changes reported by the participants in the program are potentially healthful. PMID- 1882024 TI - Psychological functioning of daughters of breast cancer patients. Part I: Daughters and comparison subjects. AB - Sixty daughters of mothers with breast cancer were matched for age, educational level, and race with 60 comparison subjects without a maternal history of breast cancer to assess the impact on psychological adjustment, coping, body image, sexual functioning, and health knowledge and practices of having had a mother with breast cancer. Daughters of breast cancer patients showed significantly less frequent sexual intercourse, lower sexual satisfaction, and greater feelings of vulnerability to breast cancer, and they could identify a greater number of symptoms of breast cancer. No differences between groups were found in psychological symptoms, coping styles, breast self-examination practices, mammography practices, health knowledge, or body-image ratings. Contrary to clinical studies, women at risk for breast cancer showed good overall coping with few signs of significant dysfunctions in relation to comparison subjects. PMID- 1882026 TI - A fallacy of subspecialization in psychiatry. Consultation-liaison is a supraspecialty. PMID- 1882027 TI - Panic disorder in a paraplegic patient. PMID- 1882028 TI - A family systems approach to competency evaluations in the elderly. PMID- 1882029 TI - [Roman medicine and classical philology. A necessary matrimony]. PMID- 1882030 TI - [History of immunology]. PMID- 1882031 TI - [Giacomo Andrea Giacomini: a Padua clinician between metaphysics and science]. AB - As Professor of Theoretical Medicine for Surgeons at Padua University between 1824 and 1849, Giacomini achieved a position of great academic professionalism and prestige, not only in Padua, but throughout Italy and Europe. His fundamental medical thesis became part of the established field of medical practice that existed into the first decades of the 19th century. This thesis, derived directly from a vitalistic concept of biological phenomena, was based on the existence of a 'life force' that is distinct from the forces of physical-chemistry, having its own specific laws, contrary to those of physical-chemistry. Using this concept Giacomini was able to distinguish two causes of death: mechanical illness and dynamic illness. The nosographic and therapeutic beliefs of Giacomini were based on his distinction between the 'mechanical' or 'dynamic' effects of drugs. Giacomini's medical philosophy is the result of an interweaving of scientific theories and metaphysical ideas. The merits and limits of this philosophy must be analysed in the light of modern epistemology to explain why Giacomini was unable to develop fully clinical anatomy. PMID- 1882033 TI - Accelerated forced eruption as a preparatory measure for the restoration of severely damaged maxillary incisors: a case report. AB - Restoration of severely damaged teeth requires comprehensive, carefully planned pretreatment. This report of a patient who sustained traumatic injury to the maxillary anterior teeth demonstrates the use of accelerated forced eruption to strengthen damaged roots, allowing placement of crowns and eliminating the need for a fixed partial denture. PMID- 1882032 TI - Streptomycin: discovery and resultant controversy. AB - The antibiotic streptomycin was discovered soon after penicillin was introduced into medicine. Selman Waksman, who was awarded the Nobel Prize for the discovery, has since generally been credited as streptomycin's sole discoverer. However, one of Waksman's graduate students, Albert Schatz, was legally recognized as streptomycin's co-discoverer and received a share of the royalties from the drug. The aim of this essay is to discuss the streptomycin story, largely using previously unquoted archival material, and in particular to provide further evidence for the important role which Schatz played in the discovery. PMID- 1882034 TI - Overdenture supported by osseointegrated fixtures: a case report. AB - The increasing use of oral endoprostheses has offered new alternatives for fixed and removable prosthesis design. However, the use of implants also requires the complex understanding and use of sound prosthodontic principles. The establishment of proper maxillomandibular relationships (vertical dimension, occlusal plane, curve of Spee, tooth arrangement), esthetics, and function are essential precursors to success. Although the usefulness of rehabilitation with overdentures supported by osseointegrated fixtures is sometimes underestimated, overdentures provide an adequate treatment alternative in indicated cases. A case is presented in which previous preprosthetic surgery had failed and subsequently an overdenture supported by osseointegrated fixtures was constructed. PMID- 1882035 TI - Improved retention for bonded cast metal rests: a case report. AB - This article describes improvements in retention of resin-bonded, cast metal rest seats that utilize cast pins for additional stabilization and resistance to intraoral forces of dislodgment. This method combines the classic design of pin ledge retainers with the resin-bonded concept of retention to provide a reliable and stable, but conservative, method of altering tooth form to support removable partial dentures. PMID- 1882036 TI - The superior labial frenum: a histologic observation. AB - Superior labial frena obtained from cadavers or frenectomies were examined histologically. The frena were covered by stratified squamous nonkeratotic, orthokeratotic, or parakeratotic epithelia, depending upon the gingival extent of the frenum. In addition to the normal components of dense, irregular, collagenous connective tissue, almost all frena contained myelinated nerve fiber bundles and small vascular channels. Additionally, 35% of the frena examined contained a few small skeletal muscle fibers. PMID- 1882037 TI - Color change in light-cured resins exposed to daylight. AB - The clinical yellowing of anterior composite resin restorations with time is often the cause for their replacement. This work examined in vitro the effect of sunlight and water separately and together on color changes in the lighter shades of 16 resins. The natural radiation (ultraviolet and visible) was greater than would be expected in clinical use, and the color changes were generally only slight for most resins, as judged by standardized photographic recording and visual inspection of transparencies over time. The changes were greater when sunlight and water were combined. The light-cured surface was less affected than the distal surface. The hydrolysis action by water was particularly marked for one resin, which also showed a high release of camphoroquinone-type catalyst. Marked clinical discoloration may be as much or more affected by absorption of food colorants than by sunlight and water. PMID- 1882038 TI - Quantitative in vivo evaluation of four restorative concepts for mixed Class V restorations. AB - This study was performed in vivo over a 6-month period to assess restorative margins in Class V restorations placed with different techniques. The margins were evaluated quantitatively under the scanning electron microscope using the replica technique. Results indicated that the sandwich technique using a glass ionomer cement base and a composite resin restoration was not able to prevent marginal gaps in dentin. However, the experimental Gluma/Clearfil system resulted in a quality of dentinal margins not statistically significantly different from that of enamel margins. These in vivo findings substantiate in vitro results. PMID- 1882039 TI - Dentinal shear bond strength, microleakage, and contraction gap of visible light polymerized liners/bases. AB - The bond strength and microleakage patterns of three light-curing glass-ionomer cement liners/bases (Vitrebond, XR Ionomer, and Zionomer) were evaluated and compared to a fluoride-releasing resin (TimeLine) designed for the same use. Bond strength tests were performed at 24 hours and 7 days. At 24 hours Vitrebond, Time Line, and Zionomer had statistically significantly greater bond strengths than XR Ionomer. At 7 days, Vitrebond had a statistically significantly stronger bond than the others. Microleakage was evaluated after 24 hours of thermocycling. Vitrebond and XR Ionomer had statistically significantly less leakage than the others, while TimeLine had significantly more leakage than the others. Polymerization contraction gaps between the liners/bases and dentin were examined with scanning electron microscopy. Contraction gaps were approximately 10 microns with Vitrebond and XR Ionomer and 5 microns with TimeLine. A contraction gap generally was not observed with Zionomer. PMID- 1882040 TI - An in vitro study of the tensile strength of composite resins repaired with the same or another composite resin. AB - Interfacial tensile bond strengths of self-cured and light-activated composite resins, repaired with the same or another composite resin were measured. The bond strengths were measured as a function of age of the substrate or as a function of the adhered surface treatment. One control group of solid resin samples was tested for tensile strength. Other groups of specimens, matured for 48 hours, 7 days, and 1 year, were cut in half and ground flat before a fresh mass of composite resin was added. Six groups were coated with a thin layer of intermediate resin or bonding agent before the fresh composite resin was added. In general, the repaired composite resins revealed lower strength than did the cohesive samples, with bond strengths ranging from 19% to 52% of the strengths of the unrepaired resins. The intermediate resin increased the bond strength in all cases. PMID- 1882041 TI - Clinical and morphologic response to interdental brushing therapy. AB - The interdental papilla is the anatomic site most susceptible to periodontal disease. The gingival epithelium plays an important role as a barrier to protect the underlying connective tissue from exogenous noxious agents. A study was undertaken to evaluate the papillary epithelial response to reconstructive stresses conducted by gingival brushing (oral therapy) and scaling and root planing, intended to induce a keratinization associated with reduction or resolution of connective tissue inflammation. Results showed that patients who prolonged the interproximal hygiene practices for more than 30 minutes a day achieved a satisfactory keratinization of the papillary gingival epithelium. PMID- 1882042 TI - A clinical technique for bonding gold castings to teeth. AB - A clinical technique is presented that allows practitioners to use adhesive bonding techniques to improve the retention and seal of gold castings. At the time of delivery of a gold casting, the preparation is treated with a self-curing enamel and dentinal bonding agent. The internal surface of the casting is sandblasted and electroplated with tin to produce a surface suitable for bonding with a resin cement, which is virtually insoluble and is adhesive to both the metal surface and the treated tooth. PMID- 1882043 TI - Maintenance of pulpal vitality using potassium nitrate-polycarboxylate cement cavity liner. AB - Following deep restorations in vital teeth, postoperative pain of various durations frequently occurs, even if the teeth were asymptomatic before treatment. In this study, a potassium nitrate-polycarboxylate cement was used as a liner and was found clinically to tend to preserve pulpal vitality and significantly eliminate or decrease postoperative pain. PMID- 1882044 TI - Nightguard vital bleaching: how safe is it? AB - The conservative technique for bleaching vital teeth using a nightguard and a 10% carbamide peroxide solution has captured the esthetic interests of the dental profession. The purpose of this article is to assess the safety of the products used in this bleaching technique based on results from past related research and current research. Ten percent carbamide peroxide solutions used in numerous studies have demonstrated tissue-healing properties as well as a propensity for the reduction of plaque and gingivitis. None of these clinical studies revealed any untoward or detrimental side effects, and all demonstrated beneficial effects. Although some concern exists regarding the potentiating effects of peroxide solutions in the presence of known carcinogens, concerns of toxicity or damage to hard and soft tissues appear unfounded. The majority of current and past research and literature indicates that the current use of a 10% carbamide peroxide solution in the method advocated for bleaching vital teeth is apparently safe when administered properly under the supervision of a dentist. PMID- 1882045 TI - Factors affecting the process of color matching restorative materials to natural teeth. AB - Resin-based restorative materials have to not only function properly but also fulfill esthetic demands; restorations must harmonize in shape and shade with natural teeth. The human perception of color is affected by external factors. The influence of these factors is discussed in regard to two pairs of composite resins: Silux/Valux and Pekalux/Pekafill. With the knowledge of the influence of these factors and with the accuracy of modern color measurement instruments, it is today possible to carry out restorative work to meet the highest esthetic standards. PMID- 1882046 TI - Faculty differences in replacement decisions for amalgam restorations. AB - During a 15-week period, six full-time faculty members supervised the replacement of amalgam restorations by clinical dental students. The tooth numbers, the amalgam surfaces replaced, the reasons for replacement, and the instructors were compared. The students removed 956 surfaces of amalgam from 436 teeth. The primary reasons cited for replacement were marginal breakdown (69%) and caries (33%). PMID- 1882047 TI - Occlusal plane modification of an existing maxillary complete denture prior to removable partial denture construction: a case report. AB - Success in fabricating removable partial dentures, Kennedy Class I and Class II in particular, is highly dependent on proper orientation of the occlusal plane. The closer to the ideal, the better the prosthesis will function and provide proper esthetics and phonetics. This case report presents the diagnosis and occlusal modification of an existing maxillary complete denture to improve the patient's masticatory function with the fabrication of a removable partial denture. PMID- 1882048 TI - Cementation of a fixed orthodontic appliance. AB - Cementation of a fixed orthodontic appliance requires careful attention to detail. Certain procedures can be used to improve fit of the stainless steel band and enhance the cementing procedure. This paper outlines a technique for cementation that optimizes the chances for an ideal long-term band-cement-tooth bond. PMID- 1882049 TI - Integrating dental and medical care for the chronic bulimia nervosa patient: a case report. AB - Excessive tooth erosion and resulting sensitivity and esthetic concerns are well documented problems in patients with eating disorders. Several techniques for restoring lost tooth structure have been reported in the literature. However, the potential significant role of dental care in the comprehensive treatment of the chronically bulimic patient has received little attention. Integration and coordination of dental treatment with medicopsycho-social therapy of the bulimic patient may enhance the patient's success in combating this complex disorder. The key to proper dental management is a definitive approach to data collection and close coordination among all health care personnel providing primary health care therapy. A specific dental approach model is recommended in this report of a patient with a 15-year history of bulimia. PMID- 1882050 TI - Multifocal Langerhans cell histiocytosis of the jaws: a case report. AB - Langerhans cell histiocytosis is an uncommon disease that includes a spectrum of disorders in which there is an abnormal proliferation of Langerhans cells. This article describes a case of a benign form of multifocal Langerhans cell histiocytosis of the maxilla and mandible. The patient was followed for a period of 2 1/2 years, during which time there was spontaneous remission of some of the lesions. PMID- 1882051 TI - Microleakage at gingival margins of Class V composite resin restorations rebonded with various low-viscosity resin systems. AB - The failure of a composite resin restoration to seal at its interface with unetched tooth structures, resulting from polymerization shrinkage, creates an unwanted marginal microleakage. Rebonding with a low-viscosity resin system has been recommended to reseal the marginal gap and to reduce microleakage. Since no particular resin system is commercially available, any low-viscosity resin has been utilized for this purpose. However, findings of this study seem to indicate the importance of selecting the appropriate resin system to optimize the outcome of this rebonding procedure, emphasizing the lowest viscosity and good wettability of the system. With proper selection of the resin system, this rebonding procedure can significantly reduce the microleakage at gingival unetched margins of Class V composite restorations. PMID- 1882052 TI - The effect of thermocycling on the hardness of soft lining materials. AB - This investigation studied the effect of thermocycling on the hardness of six commercially available soft lining materials. The apparatus used to measure hardness measured the difference between depth of penetration of an indentor into a specimen under a primary contacting load and a secondary penetrating load. Control specimens were stored in water at 20 +/- 2 degrees C and trial specimens were thermocycled between 18 +/- 1 degree C and 53 +/- 1 degree C for periods up to 28 days. It was found that thermocycling had a deleterious effect on the softness of all six materials. Further, it was shown that chairside provisional soft lining materials demonstrate a rapid deterioration at temperatures greater than 50 degrees C. PMID- 1882053 TI - Factors affecting the stability of sodium hypochlorite solutions used to disinfect dental impressions. AB - Increased concern over the transmission of acquired immunodeficiency syndrome, hepatitis B, herpes, and other diseases has prompted research into the disinfection of dental impressions. Among the factors to be considered when dental impressions are disinfected is the stability of the disinfectant solutions during storage and use. This study is concerned with the effect on disinfectant solutions of repeated immersion of alginate dental impressions taken in metal trays. The effects of the impression materials, metal trays, and dilution were evaluated, and the impact of light, heat, and storage were also addressed. The findings indicated that in the test solutions, although considerable chlorine was consumed during the disinfection procedures, bactericidal activity was maintained, while in the control solution both chlorine content and bactericidal activity were remarkably stable. PMID- 1882055 TI - Tensile resistance of complete cast crowns cemented on amalgam foundations retained by amalgapins. AB - An in vitro study was conducted to examine the influence of the number of remaining cusps and the use of the amalgapin technique on the tensile resistance of complete cast crowns in posterior teeth. Results showed the number of amalgapins and remaining cusps to have no influence on the tensile strength. Failure occurred predominantly at the cemented area (ie, the crown was dislodged from the core). PMID- 1882054 TI - Extraction versus periodontal-orthodontic treatment: a case report. AB - This paper reports the management of a patient with severe localized periodontitis accompanied by drifting and extrusion of a central incisor. Although the traditional treatment approach to this condition often includes extraction and prosthetic replacement, the approach presented here provides an alternative to extraction by combining periodontal and orthodontic treatment. PMID- 1882056 TI - Graphic assessment of interincisal point movements during chewing of hard and soft foods. AB - Interincisal point movements in 35 healthy, dentate subjects were investigated with an electrognathic apparatus. The main focus of the study was to find the average values of determined point graphic assessment in frontal and sagittal planes during chewing of hard and soft foods. However, as this was insufficient to obtain information on areas where occlusal contacts were reached, border movement envelopes were also recorded to obtain indirect information in connection to the previous task. The results showed that the graphic assessment form of mandibular movements was dependent on the consistency of the food that was chewed. PMID- 1882057 TI - Predictable seating of the single-unit cast restoration. AB - Prior to cementation, a cast restoration must be clinically evaluated in a number of critical areas. The proximal contacts and internal surface of the casting, as well as centric and excursive occlusion, require assessment and generally require adjustment before cementation. The time necessary to accomplish these adjustments is not predictable. A technique is presented that permits the majority of these adjustments to be completed in the laboratory, thus minimizing the clinical time required to seat the casting. PMID- 1882058 TI - The effectiveness of sodium fluoride iontophoresis in patients with sensitive teeth. AB - This study investigated the use of iontophoresis in altering the sensitivity level of teeth that displayed thermal and tactile hypersensitivity. A total of 95 teeth were treated with an iontophoresis instrument. Forty-eight of these teeth were treated with a placebo of deionized water, and 47 were treated with a 2% sodium fluoride solution. Two of the 47 teeth receiving sodium fluoride had identical pretreatment and posttreatment sensitivity ratings, while 40 teeth (85.1%) demonstrated a reduction in sensitivity. Twenty-nine of the 48 teeth receiving the placebo demonstrated no change in sensitivity. All teeth receiving the placebo were re-treated with sodium fluoride. Forty-seven (97.9%) responded with reduced levels of sensitivity. PMID- 1882059 TI - Effect of a new resin inlay/onlay restorative material on cuspal reinforcement. AB - Nine maxillary premolars were restored with composite resin inlays involving large intracoronal cavity preparations. Buccal and lingual bonded strain guages measured the cuspal flexure under a carefully controlled application of occlusal force. The intact tooth was compared with the corresponding preparation and final restoration. The preparation itself greatly reduced the coronal rigidity, but this was completely recovered in the restored tooth, within the functional force of 111 N. A stiffness ratio showed a 97% recovery. From the point of view of cuspal strength, this may mean that larger intracoronal restorations are feasible with this type of restoration. However, other factors, such as chairside time and complexity, and material properties, such as occlusal wear, have to be taken into consideration. PMID- 1882060 TI - Metallurgical evaluation of a copper-based alloy for dental castings. AB - The present study was designed to evaluate the metallurgical properties of an experimental, low-cost copper-zinc-aluminum-nickel alloy for dental castings. Some specimens were subjected to heat treatment after induction casting. The extent of corrosion was determined by measuring weight loss of specimens stored in a sodium sulfite solution. In the as-cast specimens, tests demonstrated the presence of three phases: the first consisted of copper-zinc-aluminum, the second was similar but lower in copper and aluminum, and the third consisted of an intermetallic compound of manganese-nickel-phosphorus. After heat treatment, the first phase remained relatively constant, the second was converted to Cu3Al, and the third increased in volume. The weight loss from the as-cast specimens was eight times that of the heat-treated specimens. It was concluded that the heat treatment substantially changed the microstructure and improved the corrosion resistance of the experimental alloy. PMID- 1882061 TI - A new profilometric method for determination of enamel and dentinal abrasion in vivo using computer comparisons: a pilot study. AB - A technique, sensitive enough to determine both dentinal and enamel abrasion in vivo, is presented. Computer-aided profilometry was used to measure the surface of dentinal and enamel samples before the experiment. Samples were subsequently placed in the buccal flanges of the mandibular dentures of two test subjects, who then brushed these pieces with a soft, multitufted brush, and two different toothpastes. Results of these pilot studies showed that the samples brushed with Colgate BiFluor had markedly less enamel and dentinal abrasion than did those brushed with Smokers. In addition, surface roughness was greater in the specimens brushed with Smokers. However, person-to-person variation can have a great influence on the abrasion process; moreover, only two persons were involved in this pilot study, and no definitive statement can be made about the effect of the toothpastes. PMID- 1882062 TI - The effectiveness of a layered baseplate training aid in the preclinical instruction of second-year dental students. AB - The effectiveness of the Cavidrill baseplate in the training of second-year dental students in cavity preparations in primary ivorine teeth was assessed. The preclinical class of 112 students was divided into four groups: Cavidrill-only group, two groups combining Cavidrill training with traditional typodont training, and a typodont-only group. The Cavidrill baseplate was found not to improve the students' performance in cavity preparation when assessed on midterm and final examinations. PMID- 1882063 TI - Benefits of increasing focal film distance. AB - As funding for high technology equipment decreases, diagnostic imaging will experience a notable renewal. Radiographers must improve the image quality and reduce the integral dose patients receive. By increasing the focal film distance from 40 inches to 50 inches, the authors have significantly increased the image quality and reduced the integral and cumulative dose of radiation by 12.5 percent. PMID- 1882064 TI - Technique for detecting early rheumatoid arthritis. AB - The authors are of the opinion that the controversy surrounding the value of radiography in the early diagnosis of RA and subsequent assessment of drug therapy is due to the poor resolution of the radiographs used in many of these studies. Given that radiographic findings correlate with the pathological changes occurring in the hands and wrists of the RA patient, the ARA 1987 revised criteria for the classification of RA requires a PA projection of the hands and wrists. With this in mind, it is obvious that a standard radiographic technique offering high-resolution be developed and implemented. Direct magnification procedures as previously described offer high-resolution, however, they are either too cumbersome to use, require specialized, limitedly available equipment, produce partial images, have prolonged exposure times leading to part motion and are too expensive. In addition, radiation dosages to the skin are higher. These problems also preclude their use in the establishment of screening procedures for early RA. By comparison, the authors' optical magnification technique eliminates the major problems encountered in direct magnification. More importantly, the described optical magnification technique provides high-resolution radiographs utilizing readily available equipment and offers a practical means for the effective screening and diagnosis of early RA. PMID- 1882065 TI - Medical ethics courses for student technologists. AB - Little has been written regarding instruction in medical ethics. Since it lies outside the familiar technical aspect of the radiologic sciences, some educators may lack confidence in presenting the subject. This article addresses the importance of adequate instruction and presents a systematic and philosophical approach for teaching medical ethics. PMID- 1882066 TI - Iceland: land of many contrasts. PMID- 1882067 TI - High tech and in touch. PMID- 1882068 TI - [Neuroradiologic exploration of cerebral arteriovenous malformations]. AB - MR and superselective neuroangiographic investigation of 223 patients with cerebral arteriovenous malformations (AVMs) were retrospectively analyzed with regard to topography, morphology, vascular architecture and signs of increased bleeding risk. MR proved highly efficient in defining the topography of the lesion and highly sensitive in detecting AVM-induced parenchymal changes. Superselective neuroangiography enables complete endovascular mapping of the AVM and provides relevant information on its intrinsic vascular composition. In addition, this method gives new insights into the venous drainage patterns and the unexpectedly high incidence of associated venous changes. MR neuroangiographic correlation in each individual case forms the basis for any therapeutic decision and treatment planning. In concordance with previous statements in the literature this study disclosed that the presence of stenotic draining veins or related aneurysms on feeding arteries represents an increased risk for AVM rupture. PMID- 1882069 TI - [Venous anomalies of the brain. The clinical significance of the so-called venous angioma]. AB - In contrast to angiography, MRI not only allows the diagnosis of DVA (developmental venous anomaly, so-called venous angioma), but also shows up cavernomas and other angiographically occult vascular malformations. It also differentiates between DVAs and occult true malformations. This has completely changed the pathological assessment of DVAs. In a retrospective study on 31 patients with angiographically proven DVAs neighbouring cavernoma was a frequent finding (15 patients, 48% group I). Symptoms caused by cavernoma were present in 6 (40%) of these 15 patients. The following associations were also found: cerebral arterial aneurysm (2), spinal arterio-venous dural fistula (1), dermal haemangioma (1), Klippel-Trenauny syndrome (1). Only 16 (52%) of the 31 cases with DVA were free of associated cavernoma (group II). Only 3 (19%) of these patients with a solitary DVA were symptomatic. In our series we have seen no case of bleeding from a DVA. A DVA is a vascular anomaly characterized, like other anomalies, by reduced resistance and limited capacity for regulation and adaptation. In rare cases this can result in haemodynamic disturbances, thrombosis and ischaemia. Wall rupture with bleeding does not occur in DVA. It must be assumed that bleeding reported in patients with DVAs before the availability of MRI resulted from an associated true vascular malformation in most cases. PMID- 1882070 TI - [MRT morphology and classification of cerebral cavernomas]. AB - An MRI review of 54 histologically verified cavernomas allowed the introduction of a system classifying this cavernous venous malformation into four types: type I (20%) corresponds to the classic morphology of a cavernoma without hemorrhage; type II (67%) is characterized by intralesional hemorrhage; type III (11%) is associated with an extra-lesional hemorrhage that compresses or displaces the cavernoma itself; and type IV (2%) corresponds to a totally calcified cavernoma. These variable cavernoma types represent different possible stages of the natural evolution of a cavernoma and limit the differential diagnosis, especially in the group of occult or cryptic cerebral vascular malformations. PMID- 1882071 TI - [Sturge-Weber syndrome. Diagnostic imaging relative to neuropathology]. AB - Clinical presentation of a child with port-wine stain and seizures leads to the suspicion of Sturge-Weber disease (SWD). This diagnosis can be confirmed by the detection of a meningeal angiomatosis. In rare cases, early detection of meningeal pathology by ultrasound has been reported. Key findings are brain atrophy, gyriform cortical calcifications demonstrated by skull radiographs after the first year of life or earlier by cranial CT, and dys- or aplasia of the deep cerebral veins on angiography. Radionuclide imaging shows focal or diffuse tracer accumulation over the affected brain regions. MR demonstrates an abnormal appearance of the affected meninges, especially thickening and pathologically increased signal intensity after Gd-DTPA application. This, in association with the demonstration of abnormal enhancement in deep medullary veins, is the most characteristic finding. Contrast-enhanced MR allows early and non-invasive diagnosis of SWD, mainly by revealing leptomeningeal angiomatosis and abnormal venous vessels. PMID- 1882072 TI - [Erdheim-Chester disease]. AB - Erdheim-Chester disease (ECD) is characterized by lipid granuloma in the long tubular bones, which leads to pathognomonic symmetrical sclerosis of their metaphyses and diaphyses. Lipid granuloma may also be present in numerous other mesenchymal tissues, especially lung, orbit and retroperitoneal space. The clinical course and prognosis of the disease depend on these lesions. Reviewing 30 cases published since 1931 and a personal case with S100 positive cells, we present the typical radiological and clinical findings. There is striking resemblance to chronic disseminated histiocytosis X. PMID- 1882073 TI - [Cerebral manifestations of Erdheim-Chester disease]. AB - Cerebral manifestations of Erdheim-Chester disease are variable, giving a picture like that of multiple sclerosis. White matter lesions are located mainly in cerebellum and pons and lipid granulomas in the meninges. An asymptomatic lesion in the choroid plexus, with prolonged uptake of Gd-DTPA is described for the first time. PMID- 1882074 TI - Molecular structure and transcriptional regulation of the salivary gland proline rich protein multigene families. PMID- 1882076 TI - Recognition of tRNAs by aminoacyl-tRNA synthetases. PMID- 1882075 TI - Amplification of DNA sequences in mammalian cells. PMID- 1882077 TI - Molecular-biology approaches to genetic defects of the mammalian nervous system. PMID- 1882078 TI - Lens proteins and their genes. PMID- 1882079 TI - Ribosome biogenesis in yeast. PMID- 1882080 TI - [Synthesis of P450 with genetic engineering and its application to drug, toxic substance, and lipid metabolism]. PMID- 1882081 TI - [Ion spray mass spectrometry for biopolymers]. PMID- 1882082 TI - Primary structure of two forms of gonadotropin-releasing hormone from brains of the American alligator (Alligator mississippiensis). AB - Two forms of gonadotropin-releasing hormone (GnRH) have been purified from brains of the American alligator, Alligator mississippiensis, using reverse-phase high pressure liquid chromatography (HPLC). The concentration of total GnRH was 8.8 ng/g of frozen brain tissue or 21.1 ng per brain. The amino acid sequence of each form of GnRH was determined using automated Edman degradation. The presence of the N-terminal pGlu residue was established by digestion studies with bovine pyroglutamyl aminopeptidase and coelution with synthetic forms of the native peptide. The primary structure of alligator GnRH I is pGlu-His-Trp-Ser-Tyr-Gly Leu-Gln-Pro-Gly-NH2 and alligator GnRH II is pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro Gly-NH2. PMID- 1882083 TI - Expression of preproVIP-derived peptides in the human gastrointestinal tract: a biochemical and immunocytochemical study. AB - In order to study biosynthetic processing of the precursor for vasoactive intestinal peptide (preproVIP) in the human gut we have developed antisera against the five functional domains of the precursor molecule: preproVIP 22-79, peptide histidine methionine (PHM), preproVIP 111-122, VIP and preproVIP 156-170. The antisera were used to quantify and characterize VIP-precursor peptides by radioimmunoassay (RIA) together with high-pressure liquid Uchromatography (HPLC) and to examine their cellular localization and colocalization by immunocytochemistry. All five peptides were expressed but not in equimolar amounts as expected from the amino acid sequence of the precursor. However, the ratios between them were fairly constant throughout the gastrointestinal tract. The only exceptions were the lower concentrations of PHM and preproVIP 111-122 in the gastric antrum which could be explained by the presence of PHV (the C terminally extended form of PHM which includes preproVIP 111-122) in large concentrations in this region. It was also found that the C-terminal lysine residue of preproVIP is not removed during processing. Immunocytochemically all preproVIP-derived peptides were shown in neuronal elements. They had a similar distribution throughout the gut suggesting coexistence, a finding which was supported by doublestaining. The findings indicate that differences in the posttranslational processing of preproVIP exist in subpopulations of neurons in the human gut. PMID- 1882084 TI - Neural influence on oxytocin-induced changes of adrenomedullary catecholamines in the pigeon. AB - Oxytocin (0.25 IU/100 g body wt) was injected intraperitoneally only once to unilaterally splanchnic denervated pigeons. The effects were investigated after 0.5, 4, 12, 24, 72, 144 and 216 h of administration. The findings revealed that oxytocin caused the release of more norepinephrine (NE) from the denervated glands up to 24 h after treatment. In contrast, oxytocin-induced release of epinephrine (E) showed no significant difference in between the innervated and the denervated glands after 0.5 h of treatment. Strikingly, oxytocin brought about release of more E from the denervated glands after 24 h of treatment. This indicates that the first phase of NE release and the second phase of E release are neurally regulated. The findings further revealed that the resynthesis of both NE and E was faster in the innervated glands after 216 h of oxytocin treatment. This clearly points out that the splanchnic nerve accelerates resynthesis of both NE and E induced by oxytocin. PMID- 1882085 TI - Rabbit neuromedin U-25: lack of conservation of a posttranslational processing site. AB - The rabbit small intestine contains neuromedin U-like immunoreactivity (22 pmol/g wet tissue weight) that was resolved into a single major molecular form by reversed-phase HPLC. The primary structure of the peptide was established as: Phe Pro-Val-Asp-Glu-Glu-Phe-Gln-Ser-Pro10-Phe-Gly-Ser-Arg-Ser-Arg- Gly-Tyr-Phe- Leu20 Phe-Arg-Pro-Arg-Asn.NH2. In rabbit neuromedin U, the Arg16-Arg17 dibasic residue processing site that is found in pig and dog neuromedin U-25 is replaced by Arg Gly, but this potential monobasic processing site is not utilized by cleavage enzyme(s) in the intestine. PMID- 1882086 TI - Neutral endopeptidase 24.11 in rat peripheral tissues: comparative localization by 'ex vivo' and 'in vitro' autoradiography. AB - The neutral endopeptidase 24.11 (NEP) also called 'enkephalinase' thanks to its inactivation of enkephalins in the brain, was also recently shown to be involved in the degradation of the circulating atrial natriuretic peptide (ANP). Inhibitors of NEP are therefore under clinical trials as new analgesics or antidiarrheal agents, protecting centrally or peripherally released opioid peptides and as novel antidiuretics and anti-hypertensives in prolonging the renal and vascular actions of NEP. It was therefore important from a clinical point of view to investigate the distribution in peripheral tissue of a systemically administered NEP blocker. Different concentrations of the radiolabelled inhibitor [3H]HACBO-Gly have been intravenously injected in rat and the distribution studied using whole-body sections at different times by 'ex vivo' and 'in vitro' autoradiography to investigate differences in tissue accessibility of NEP to a circulating inhibitor. In vivo [3H]HACBO-Gly binding was fully prevented by an excess of unlabelled inhibitor and disappeared rapidly mainly through renal elimination. NEP labelling was prominent in kidney, liver, lung, fat deposits in the neck region, the flat bones of the skull, the mandibula, the vertebrae, the long bones of the limbs, articular cartilages and synoviae. A lower labelling was found in the intestine, the glomeruli and the submaxillary glands. [3H]HACBO-Gly binds also to a limited number of peripheral tissues in which the presence of NEP was yet unknown (bones, parts of adipose tissues. Some tissues, not labelled in vivo, exhibited various degrees of labelling under in vitro conditions (the brain, some portions of the gut, the testes, the prostate). Interestingly, few lobules of the submaxillary glands were much more densely labelled suggesting the possible occurrence of NEP heterogeneity. Except for the brain, the physiological function of NEP in various tissues remains largely unknown, but this ectoenzyme is likely involved in inactivation of regulatory peptides such as: ANP (partially in the kidney), SP in the lung and possibly somatostatin and ANP in bone, ANP in adipose tissue, enkephalin in testes, immune peptidic factors in bone marrow. A part of NEP in bone marrow corresponds probably to the common acute lymphoblastic antigen, CALLA, densely expressed on pre-B cells. Finally, it is important to notice that several tissues containing important concentrations of NEP (brain, testes, prostate, eye, gut, brush border) are inaccessible to the i.v. injected inhibitor thanks to the presence of functional barriers. PMID- 1882088 TI - Corticotropin-releasing factor: an inhibitor of vascular leakage in rat skeletal muscle and brain cortex after injury. AB - Corticotropin-releasing factor (CRF) and other peptides of the corticoliberin superfamily inhibit development of edema in skin and mucosa after noxious stimuli. Here, the breadth of CRFs protective activity on small blood vessels was examined after injury to skeletal muscle or to brain cortex. Male rats (243 +/- 15 g) were anesthetized with sodium pentobarbital 60 mg/kg i.p. and Monastral blue 60 mg/kg i.v. was injected 3 min before mechanical injury to muscle produced by a 4 cm midline surgical incision in the rectus abdominis or before freeze injury to the cortex produced by applying a cold probe (-50 degrees C) to the skull for 4 min. Vascular leakage, measured as area of dye staining multiplied by its light intensity, was quantified with an image-analysis system. CRF, having the human/rat sequence, 30 micrograms/kg s.c., injected once (30 min) or twice (30 min and 10 min) before injury to muscle or to brain, inhibited the lesion size by 58% and 55%, respectively (tissues taken at 0.5 and 1 h). Microscopy showed that CRF inhibited Monastral blue labeling of small blood vessels. The ED50 (95% C.L.) of CRF for reducing vascular leakage in muscle after celiotomy was 24 (9 to 64) micrograms/kg s.c. h/rCRF injected 30 micrograms/kg s.c. 2 h before celiotomy inhibited vascular leakage after celiotomy in adrenalectomized rats and this effect was not obtained with dexamethasone phosphate, 1 mg/kg s.c. alpha-Helical CRF (9-41), a CRF receptor antagonist, attenuated the actions of CRF on celiotomy. Laser-Doppler flowmeter measurements of skeletal muscle showed that the anti-inflammatory effects of CRF occurred when there were no significant concurrent changes in blood flow. From these results, we surmise that CRF has a versatile protective effect on small blood vessels when it inhibits leakage within different vascular beds. PMID- 1882087 TI - Chromogranin B: isolation from pheochromocytoma, N-terminal sequence, tissue distribution and secretory vesicle processing. AB - The chromogranins/secretogranins are a family of neuroendocrine vesicle secretory proteins. Immunohistology and immunoblotting have suggested that a major soluble protein in human chromaffin granules may be chromogranin B (CgB). We purified from pheochromocytoma chromaffin granules an SDS-PAGE 110-120 kDa protein whose N terminal sequence matched that previously deduced from a human CgB cDNA. An antibody directed against a synthetic human CgB N-terminal region specifically recognized the CgB N-terminus, though not the chromogranin A (CgA) N-terminus or the CgB C-terminus on immunoblots. An antiserum directed against CgB's C-terminus also visualized CgB but not CgA. By immunoblotting, CgB was a quantitatively major protein in human pheochromocytoma chromaffin granules, but a relatively minor in normal bovine adrenal medullary chromaffin granules. In a variety of normal bovine neuroendocrine tissues, the relative abundance of CgB immunoreactivity on immunoblots was: adrenal medulla greater than anterior pituitary greater than pancreas greater than small intestine, hypothalamus. Immunoblotting of neuroendocrine tissues (or their hormone storage vesicle cores) with both anti N-terminal and anti C-terminal CgB antisera suggested bidirectional cleavage or processing of CgB; in the anterior pituitary, a unique 40 kDa C-terminal fragment was observed. Bidirectional CgB cleavage was also suggested on immunoblots of chromaffin tissue from three species (human, bovine, rat). C-terminal processing of CgB was also confirmed by amino acid sequencing of SDS-PAGE-separated, polyvinylidene difluoride membrane-immobilized CgB fragments from pheochromocytoma chromaffin granules. Whether such fragments possess biological activity remains to be investigated. PMID- 1882089 TI - Release of calcitonin gene-related peptide in the pig nasal mucosa by antidromic nerve stimulation and capsaicin. AB - The overflow of calcitonin gene-related peptide like-immunoreactivity (CGRP-LI) in the nasal venous effluent upon antidromic stimulation of the maxillary division of the trigeminal nerve with 6.9 Hz for 3 min or upon capsaicin (0.3 mumol bolus injection) were analysed in the nasal mucosa of sympathectomized pentobarbital anaesthetized pigs. The overflow of CGRP-LI upon antidromic stimulation displayed a slower appearance in the venous effluent than the overflow upon bolus injection of capsaicin. The vascular effects as revealed by the arterial blood flow, the venous blood flow, the blood volume of the nasal mucosa, i.e., the filling of the capacitance vessels and the superficial mucosal blood flow as revealed by the laser-Doppler signal were also studied. Antidromic stimulation of the trigeminal nerve as well as capsaicin bolus injection induced a marked vasodilation which was parallel to the overflow of CGRP. However, capsaicin bolus injection also resulted in a marked increase in the mean arterial blood pressure which may be due to reflex activation of sympathetic fibers. In conclusion, we have demonstrated that chemical stimulation with capsaicin as well as antidromic stimulation of nasal sensory nerves in sympathectomized animals induces both vasodilation and overflow of CGRP-LI in vivo. This indicates that CGRP may contribute to the sensory regulation of the microcirculation in the nasal mucosa. PMID- 1882090 TI - Patterns of immunoreactive pancreatic polypeptide in human plasma. AB - Pancreatic polypeptide (PP) is synthesized as an amino-terminal moiety of a precursor peptide and is released into plasma during stimulation as an amidated hormone (PP1-36). The purpose of this investigation was to ascertain the immunoreactive forms of PP in human plasma using HPLC chromatographic technique. Plasma was obtained from five normal volunteers under various postprandial intervals and from the Blood Bank. PP in each plasma sample was processed for HPLC analysis by immunoprecipitation and/or immunoaffinity extractions. Migration patterns of PP-forms were identified under isocratic elution. This study shows that human plasma contains four distinct immunoreactive (IR) forms of PP during stimulation by a protein-rich meal. These forms are PP1-36 (peak 4), PP3-36 (peak 3) and unidentified material migrating as peak 2 and peak 1. The corresponding migration constants were Kav 0.828 +/- 0.04, Kav 0.790 +/- 0.003, Kav 0.570 +/- 0.009 and Kav 0.409 +/- 0.007, respectively. The predominant fasting from of IR PP chromatographed as peak 1, while peaks 2 and 4 were reduced in amplitude. The 1 h and 3 h postprandial chromatograms of HPLC profiles of plasma PP were similar in shape but lower in relative magnitude and amplitude. The authenticity of peak 4 as the migration of native PP1-36 was confirmed using purified IR native PP1-36 extracted from human pancreas. Partial amino acid sequence analysis of PP peak 3 revealed deletions of two N-terminal amino acid residues. The chemical identities of peaks 1 and 2 are unknown but appear to differ from PP in peaks 3 and 4 by virtue of their migration profiles. It is concluded that there are at least four distinct IR forms of PP in human plasma. Native PP1-36 accounts for less than 1% of total PP after an overnight fast and is about 1/3 of total postprandial IR plasma PP. Discernment of the nature and etiology of forms of PP in plasma may provide a new understanding of the role of PP in mammalian physiology. PMID- 1882091 TI - Gonadotropin-releasing hormone (GnRH) analogs: relationship between their structure, proteolytic inactivation and pharmacokinetics in rats. AB - There are two types of superactive agonists of gonadotropin-releasing hormone (GnRHa-I: (D-amino acid)6-GnRH and GnRHa-II: (D-amino acid)6-(desGly)10-GnRH- ethylamide) the high hormonal activity of which is understood to be due to their higher receptor affinity and their higher proteolytic stability as compared with the native GnRH sequence. Using the soluble fractions of various rat tissues in studies on the inactivation of GnRH peptides, we confirmed the higher proteolytic resistance of GnRHa-II, but not of D-Phe6-GnRH (GnRHa-I) and of another analog, D Trp3-D-Phe6-GnRH, as compared with GnRH. The exact behaviour of the peptides during degradation was found to be dependent on the peptide concentrations used, showing the importance of using conditions as near to the physiological ones a possible. Towards the membrane fractions, however, the order of degradability was found to be GnRH much greater than D-Phe6-GnRH much greater than D-Trp3-D-Phe6 GnRH. The pharmacokinetic consequences of the different proteolytic degradabilities of the GnRH peptides, observed in rats, were a moderate increase in the biological half-life of D-Phe6-GnRH by 2.5-fold, as compared with GnRH, and a small increase in half-life of D-Trp3-D-Phe6-GnRH by 1.4-fold when compared with D-Phe6-GnRH. Whereas no intact GnRH was recovered in rat urine, small amounts of D-Phe6-GnRH (about 1% of dose) and high amounts of D-Trp3-D-Phe6-GnRH (25.5%) were excreted into urine. Combining the biochemical and pharmacokinetic data, it is concluded that proteolytic stability of GnRH analogs in pharmacological terms means stability towards membrane enzymes (pharmacologically related stability) and that designing analogs with further increased proteolytic stability will be of only limited consequences with respect to their biological half-lives, the glomerular filtration rate of the kidney becoming the determining factor in the peptide clearance. PMID- 1882092 TI - [Attaining success in our profession. Business analysis helps dentists to work smarter, not harder]. PMID- 1882093 TI - [Bases of dentinopulpal protection, current status]. PMID- 1882095 TI - ["Dental education" or censurable publicity?]. AB - The author comments on the problem of advertising in dentistry desguised as public "dental education". In the form of personal interviews to individual dentists or "scientific" articles through mass media the news on therapeutic methods, procedures or materials, usually is rather inaccurate, presenting the information almost as panaceas without a serious support. This has a negative effect on the community and is by all means unethical and punishable. PMID- 1882094 TI - [Epithelial attachment and subperiosteal implants]. AB - The case presented is a subperiosteal implantation in a human being, in chrome cobalt mollybdenum, with two years and a half of evolution. It has been studied from the morphological point of view on being extracted for the patient's request, because of a prosthetic maladjustment; the existence of a epitheliarl adhesion and the subjacen tissue reaction have been documented. PMID- 1882096 TI - [Varnishes and adhesives in the seal of silver amalgam restorations]. AB - The object of this paper is to evaluate the marginal filtration occurring between restoration/teeth in cavities filled with silver alloy when using different cavity varnish and adhesives. In 50 teeth removed as a result of decay, cavities were prepaired on vestibular faces and were divided into 5 equal groups: Group A: with no caviti varnish; Group B: two coats of a linkin agent (Scotch Bond 3M); Group C: an amalgam liner base (Voco); Group D; two coats of copal varnish: Group E: an amalgam bond base (Carl San Remo, Germany). All groups were filled with a silver alloy. The teeth were inmersed in a fuchsin solution at different temperatures (17.37 degrees C and 50 degrees C) for 20 minutes. Longitudinal cuts were made for visualization under a stereoscopic magnifying glass. Each group was observed by five odontologists and was classified according to four categories: Grade I: no filtration: Grade II: less than 1/3 wall filtration; Grade III: more than 1/3 wall filtration; Grade IV: filtration in walls and floor. Teeth with pulp filtration were discarded. Total and percentage values were determined for each analysed group. The results revealed that: Group A: 100% of samples corresponds to Grade IV. Group B: 40% of sample falls within Grade II while the rest corresponds to the highest grade. Group C: 30% belongs to Grade II, 60% to Grade III and the remaining 10% to Grade IV; Group D: 30% falls within Grade I, while the remaining 20% and 50% correspond to Grades III and IV, respectively. Group E: 50% for Grade I and the rest in Grade II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882098 TI - [Recovery of a dark radiograph]. PMID- 1882097 TI - [Orthodontic-orthopedic treatment of alveolar deficiency and maxillary retrusion]. PMID- 1882100 TI - [Globulomaxillary cyst. Presentation of a case]. PMID- 1882099 TI - [Ameloblastoma. Clinical case]. PMID- 1882101 TI - [Diagnosis and planning for osseointegrated prosthesis]. PMID- 1882102 TI - [Parafunctions of the stomatognathic system: their origins and consequences. 1]. AB - Parafunctional activities are mainly responsible for the disorders that are detected in the Stomatognathic System. Those activities have two majors etiological factors, one of those is the occlusal relationship, and the other one is the emotional strain. Muscular hiperactivity role and their mechanics, as a factor of risk in the disorders of the masticatory system, are explained. PMID- 1882103 TI - [Change in attitude toward the "affective dentist". The initial interview]. AB - The role of initial patient assessment as part of a total program designed to change negative attitudes towards the dental visit is discussed. The strategy endorsed is one which takes into account the affective component of a patient's attitude and allows for its expression trough an empathic client-centered itake. Two case studies area presented as illustrations of this approach. PMID- 1882104 TI - [Canal infection. Ecological theory and repair with osteodentin]. AB - The characteristics of the infection in the root canal are analyzed, specially its development before pulpal necrosis. It is inferred that it is an ecological infection with a function: to decompose the necrosis. Inactivating the infection in the canal by the formocresol technique, calcium hidroxide or with the conventional basic treatment in Endodontics, cleaning, washing, disinfecting and, in this case, with partial obturation of the canal, it is possible to induce a reparation with osteodentine that can cover all the free extension of the canal. PMID- 1882105 TI - Tuberculosis--on the increase? PMID- 1882106 TI - Bronchiolitis obliterans, cryptogenic organising pneumonitis and BOOP. PMID- 1882107 TI - Smoking and prevention. PMID- 1882108 TI - Reversible T-wave abnormality in severe acute asthma: an electrocardiographic sign of severity. AB - Reversible electrocardiographic (ECG) abnormalities are well recognized in severe acute asthma. Inferior lead T-wave abnormalities have only rarely been reported, and their frequency and significance have not been well documented. We studied 70 consecutive patients with severe acute asthma on admission to hospital and during recovery, in order to examine the frequency and natural history of such changes and to document their relationship to the severity of the attack. Twenty-two patients (34%) had inferior lead T-wave inversion on ECGs performed within 1 h of admission (group 1), whereas the rest did not (group 2). Apart from sinus tachycardia this was the most common ECG abnormality. Patients with inferior T wave inversion were found to have more severe asthma in terms of degree of pulsus paradoxus, peak expiratory flow rate, forced expiratory volume in 1 s and arterial blood oxygen tension. Ten group 1 and ten group 2 patients underwent two dimensional echocardiography during the acute phase of their illness and during recovery. Six (60%) group 1 patients showed echocardiographic evidence of right ventricular pressure overload compared with only one (10%) patient in group 2 (P less than 0.02). Following recovery, voluntary hyperventilation and exercise testing in ten group 1 patients failed to reproduce the ECG changes seen on admission. Reversible inferior lead T-wave abnormalities may occur in the severe acute asthma and appear to be related to the severity of the attack. PMID- 1882109 TI - Assessment of asbestos-induced pleural disease by computed tomography- correlation with chest radiograph and lung function. AB - We compared computed tomography (CT) scanning with chest radiography in the assessment of asbestos-induced pleural disease (AIPD) in 20 patients (17 men and 3 women, mean age 55 years, range 43-74 years). Involved pleura was scored on plain chest radiographs according to the International Labour Office (ILO) method of evaluating AIPD. A CT score was calculated from the measurement, using a digital length probe, of the circumference of the chest wall involved by pleural disease in each slice. The maximum width of pleural disease was taken into account in a way analogous to the ILO method for the chest radiograph. The CT score correlated with the chest radiograph score (r = +0.82, P less than 0.0006). CT demonstrated discrete plaques in 95% of patients but these were identified only in 59% patients on the radiograph. Diffuse pleural thickening was evident on the CT scan in all patients and in 70% on the radiograph. There was more inter reader agreement about the type of pleural disease on the CT scans than on the chest radiographs. CT and chest radiograph scores inversely correlated with all lung function measurements except KCO. We conclude that increasingly extensive pleural disease is associated with increasingly severe impairment of lung function. CT scanning demonstrates the type of AIPD better than plain chest radiography. PMID- 1882110 TI - Maximal inspiratory and expiratory mouth pressures in sitting and half-lying positions in normal subjects. AB - Maximal inspiratory (PImax) and expiratory (PEmax) mouth pressures were measured in seven normal adults in both sitting and half-lying positions on 2 days. Analysis of variance did not reveal significant differences between measurements made in the two positions for either PImax or PEmax. Measurements were repeatable and the results obtained in both positions were pooled. The coefficient of variation of PImax was 4.7% between-trials and 10.3% between-days, and those for PEmax were 3.4% and 4.4%, respectively. It is suggested that measurements of PImax and PEmax made in the half-lying position after thoracic surgery can be compared to pre-operative values which are commonly obtained in sitting without any influence from a positional effect. Details of the methodology to improve the reliability of the respiratory mouth pressures technique are discussed. PMID- 1882111 TI - Mycobacterium kansasii infections in Western Australia (1962-1987). AB - The records of 81 patients with isolations of Mycobacterium kansasii in Western Australia over 26 years have been reviewed. Thirty-nine individuals with 40 episodes of infection were considered to have disease due to M. kansasii: 36 in the lungs (90%), two in the joints (5%), and one each in the skin (2.5%) and the lymph nodes (2.5%). The average incidence rate per 100,000 per year was 0.14 for the state with the highest in the Geraldton Mid-west region (0.57). The male:female ratio was 4:1 and the mean age 50 years (SD 14.5). For pulmonary disease the male:female ratio was 3.5:1, the mean age 53 years (SD 11), 42% being miners or ex-miners and 91% smokers or ex-smokers. Almost 97% of those infected were Caucasian and none were Aboriginal. Drug treatment was highly successful, particularly with the rifampicin/ethambutol combination, where 12 months appeared to be adequate. There are differences in the demography of the patients having pulmonary disease compared to the 42 with insignificant isolations. PMID- 1882112 TI - Endobronchial biopsy positive sarcoidosis: relation to bronchoalveolar lavage and course of disease. AB - Sixty-two patients with newly diagnosed sarcoidosis were examined with fibreoptic bronchoscopy, endobronchial biopsies and bronchoalveolar lavage (BAL) were analysed. Epithelioid granulomatosis in endobronchial biopsies were found in 28 (45%) of the patients (BPOS). The patients in this BPOS group showed higher inflammatory activity in BAL fluid compared to those with negative biopsies (BNEG), with significant increases in lymphocyte and mast cell counts, and concentrations of procollagen III peptide and albumin. The patients were followed over a period of 2 years. The BPOS group tended to have a worse clinical course with more patients having a progressive disease and more patients requiring treatment with systemic steroids. We conclude that the findings of epithelioid granulomatosis in endobronchial biopsies may reflect a more intense and widespread inflammation in the lung. PMID- 1882113 TI - Neonatal respiratory distress and lung function at follow-up. AB - Eight infants (gestational age 27-32 weeks) ventilated in the neonatal period had significantly higher airway resistances at 6 months, but not 1 year, than eight infants matched for gestational age but without any neonatal respiratory problems. We conclude that neonatal ventilation or respiratory distress causes a temporary impairment of lung function. PMID- 1882114 TI - Inter-relations between relapses, drug regimens and compliance with treatment in tuberculosis. AB - The inter-relationships between relapse, treatment regimen and compliance in 1009 patients treated for tuberculosis between 1978 and 1987 are reported. Multiple linear logistic regression using relapse as the dependent variable was used because of the complex relationships between treatment, compliance, age and calendar year of treatment. Compliance (P less than 0.0001) was the major determinant of relapse, but age (P = 0.047) was also significantly associated. Relapse was not related to sex, site of disease, ethnic group or the presence of multiple disease sites. Although the regimen given, the total duration of treatment and treatment with or without pyrazinamide were not statistically associated with relapse, pyrazinamide containing regimens were associated with better compliance. Compliance was best in those aged 60 years and over and worst in those aged 15-29 years. Some of the non-compliance leading to relapse was only uncovered by close Health Visitor surveillance and not by the physician supervising treatment, emphasizing the important role of field staff in patient follow-up. PMID- 1882115 TI - Rheumatoid arthritis and cryptogenic organising pneumonitis. AB - We describe three patients with rheumatoid arthritis who presented with non specific pulmonary symptoms, a restrictive defect in lung function and bilateral changes on chest radiograph. Lung histology showed characteristic features of cryptogenic organising pneumonitis and treatment with steroids produced significant improvement. The clinical and laboratory features of cryptogenic organising pneumonitis (otherwise known as bronchiolitis obliterans organising pneumonia, 'BOOP') are discussed and compared with those of bronchiolitis obliterans with which the condition should not be confused. Cryptogenic organising pneumonitis should be considered as one of the pulmonary manifestations of rheumatoid arthritis, but lung biopsy is essential to make the diagnosis. PMID- 1882116 TI - Late phase nasal reactions--reviewed and revisited. PMID- 1882117 TI - Recurrent pneumothorax and malignant pleural mesothelioma. PMID- 1882118 TI - Lung function and diabetes. PMID- 1882119 TI - Heated linoleic acid anilide reduces serum enzyme activities in rats. AB - In view of possible involvement of fatty acid anilides in toxic oil syndrome (TOS), the effects of linoleic acid anilide (LAA) and heated linoleic acid anilide (HLAA) on the activities of serum enzymes following their oral administration was studied in rats as a function of time. Serum glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities decreased significantly in both LAA and HLAA treated rats at day 4. The decreases, however, were confined to only HLAA treated group at later stages with GOT activity showing significant decrease at day 8 and total lactate dehydrogenase (LDH) as well as GOT and GPT activities at day 12. Liver GOT activity at day 4 and LDH activity at day 8 decreased significantly in both LAA and HLAA treated rats. These findings indicate HLAA components may interact with plasma membranes and thereby, reducing the secretion of the enzymes into the serum. PMID- 1882121 TI - Effects of Fe2+, Fe3+ and desferrioxamine on paraquat accumulation by rabbit kidney cortex slices. AB - Effects of Fe2+, Fe3+ and desferrioxamine (DFO) on the accumulation of paraquat (PQ) into rabbit kidney cortical slices were studied. Fe3+ showed dose-dependent inhibition of PQ accumulation. Fe2+ had a more powerful stimulatory effect on the lipid peroxidation of cortical slices than Fe3+, but it did not reduce PQ accumulation. The addition of DFO made the inhibitory effect of Fe3+ on PQ accumulation more pronounced. These results suggest that Fe3+ is able to inhibit the accumulation of PQ independent of its peroxidative action, and that Fe(3+) desferrioxamine (ferrioxamine) may serve as an antidote for the toxicity of PQ. PMID- 1882120 TI - Neurotoxicological effects of a pyrethroid formulation, fenvalerate in rats. AB - The effect of systemic treatment of a synthetic pyrethroid insecticide, fenvalerate (FV) was examined in adult female rats at different doses i.e. 5, 10, 20 mg/kg body weight by gavage for 21 consecutive days on regional brain levels of noradrenaline (NA), dopamine (DA), their acid metabolites: dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) by HPLC-EC system. Our results demonstrate pronounced inhibition of NA, DA, HVA & DOPAC levels in several brain regions which were neither dose related nor region specific. PMID- 1882122 TI - Interaction between dual NADPH-dependent reactions of paraquat in mouse brain microsomes. AB - Paraquat stimulated NADPH-dependent lipid peroxidation in mouse brain microsomes, while it suppressed lipid peroxidation induced by NADPH plus ascorbate. The stimulation of lipid peroxidation by paraquat was inhibited by N-ethylmaleimide (NEM). However, NEM attenuated the inhibitory effect of paraquat on lipid peroxidation elicited by NADPH in combination with ascorbate. These results suggest that an NADPH-dependent reaction which is susceptible to NEM might share an electron from NADPH with the alternative reaction, lipid peroxidation, in the presence of paraquat in mouse brain microsomes. PMID- 1882123 TI - Effects of gastrointestinal hormonal peptides on the transformation of human peripheral lymphocytes. AB - The gastrointestinal peptides secretin and cholecystokinin were found to inhibit the incorporation of 3H-thymidine in the lymphocyte transformation reaction in response to phytohemagglutinin. Both peptides inhibited lymphocyte activation in a dose responsive fashion. This inhibition was not due to the toxicity of these substances, as the lymphocytes remained intact and capable of excluding trypan blue. Neither glucagon nor gastrin had any effects of lymphocyte transformation. PMID- 1882124 TI - Production of self-migration stimulating factor by metastatic human malignant melanoma cells established in culture. AB - Establishment of human malignant melanoma of hard palate cell line derived from metastatic foci in lymph node is reported. We name it HM162. The shape of HM162 was almost spindle. HM162 cells secreted a factor into culture medium which stimulates motility of HM162 cell itself, and the mode of stimulated migration of HM162 cells were activated random migration, that is chemokinesis. PMID- 1882125 TI - Dose-dependent glucocorticoid effects on noradrenergic synaptogenesis in rat brain: ontogeny of [3H]desmethylimipramine binding sites after fetal exposure to dexamethasone. AB - Glucocorticoid administration slows the development of many types of cells, but may selectively accelerate differentiation of catecholaminergic cells. In the current study, pregnant rats were given dexamethasone on gestational days 17, 18 and 19 and noradrenergic synaptogenesis assessed in the offspring by measurements of binding capabilities for [3H]desmethylimipramine (DMI), a radioligand probe for noradrenergic presynaptic terminals. After treatment with 0.05 mg/kg of dexamethasone, a dose that did not suppress body or brain region growth, [3H]DMI was initially enhanced in midbrain + brainstem and in cerebellum; the former region also displayed a secondary phase of augmented [3H]DMI binding during the ontogenetic peak occurring in the second to third postnatal week. At a higher dose (0.2 mg/kg) that elicited moderate growth impairment, fetal dexamethasone exposure produced biphasic effects on [3H]DMI binding: initial enhancement was still apparent in cerebral cortex and cerebellum, but there were subsequent deficits in binding and the peak in midbrain + brainstem was shifted to later stages. At the highest dose (0.8 mg/kg), profound growth impairment was evident and only the cerebellum showed unequivocal evidence of enhanced [3H]DMI binding. All changes were associated with alterations in the maximum [3H]DMI binding capacity (Bmax) not in the binding affinity (Kd). These results suggest that low doses of dexamethasone that do not suppress general growth, enhance noradrenergic synaptogenesis in a regionally-selective and age-selective manner; at higher, growth-suppressing doses, this effect is intermixed with general delays in maturation, likely contributing to the variable effects of glucocorticoids on neurobehavioral development. PMID- 1882126 TI - An indirect method demonstrating that CCl4-dependent hepatocyte injury is linked to a rise in intracellular calcium ion concentration. AB - The capacity of CCl4 to activate phospholipase A2 (PLA2) of isolated hepatocytes in suspension, and the toxicity of CCl4 against such hepatocytes, was confirmed. It was shown that these actions of CCl4 are independent of the concentration of Ca2+ ions in the suspension medium over a 25,000-fold range. In particular, toxicity of CCl4 does not require high Ca2+ in the suspension medium. The Ca(2+) ionophore A23187 can also activate PLA2, and it also is toxic. However, in this case activation of PLA2 and toxicity require a high medium Ca2+ ion concentration. These radically different modes of action of CCl4 and A23187 permitted an indirect confirmation of the hypothesis that the activation of PLA2 by CCl4, and the toxicity of CCl4 depend on CCl4-dependent mobilization of intracellular stores of Ca2+, and a rise in the concentration of Ca2+ ions in the hepatocyte cytosol. PMID- 1882127 TI - Effect of hypothermia on cyclophosphamide-induced cytological and biochemical changes in mice. AB - Swiss albino mice, 6-8 weeks old were treated intraperitoneally with an aqueous solution of cyclophosphamide. Control group of mice were treated with distilled water. All animals were maintained either at 4 or 22 degrees C and sacrificed after 24, 48 and 72 hours of treatment. Femoral cells were screened for induction of micronuclei. Protein, RNA and DNA were determined in liver cells of the same animals. Exposure to cold was found to reduce the cyclophosphamide-induced micronuclei in the polychromatic cells and increase the quantity of protein, RNA and DNA in the liver cells. The observed inhibition of micronuclei may be due to increased serum levels of melatonin, taurine, hypotaurine or thyroxine under hypothermic conditions. PMID- 1882128 TI - Effects of meclofenamate on natural killer cell activity. AB - The effect of meclofenamate on natural killer cell activity was studied in a four hour 51Cr release assay. Meclofenamate, a nonsteroidal anti-inflammatory drug, had no effect on natural killer cell activity when added to the mixture of target (K562) and effector (peripheral blood mononuclear) cells either at the beginning of the reaction or when effector cells were pretreated with meclofenamate for 12 24 hours. However, a significant increase (p less than 0.0005) in the natural killer cell activity was seen when target cells were pretreated with meclofenamate for 12-24 hours prior to their mixing with effector cells. This increase in natural killer cell activity was observed consistently when target cells were taken from different donors. PMID- 1882129 TI - Effect of sodium chloride on pirarubicin induced cell killing in P388 mouse leukemia cells. AB - The effect of sodium chloride on the cytotoxicity of 4'-O tetrahydropyranyldoxorubicin (pirarubicin), a novel anthracycline derivative, was investigated on P388 mouse leukemia cells in vitro. The modifications in efficiency of uptake and killing action of pirarubicin were found to be dependent on the ionic strength of the medium. The relationship between intracellular drug accumulation into cells and cell killing was pointed out. PMID- 1882130 TI - Hepatotoxicity of eugenol and related compounds in mice depleted of glutathione: structural requirements for toxic potency. AB - Eugenol produces hepatic injury in mice depleted of glutathione (GSH) by pretreatment with buthionine sulfoximine (BSO). Several eugenol analogs were examined for their ability to cause hepatic injury after administration to mice in combination with BSO. Hepatotoxicity was assessed by measuring relative liver weight, liver blood volume, and serum GPT activity in mice. Comparison of the tested compounds showed that the structural requirements for toxic potency was a phenolic ring having an allyl substituent at the 4-position. These structural requirements can be explained by assuming that a vinylogous quinone methide formed by metabolic oxidation of eugenol plays a role in inducing hepatotoxicity in GSH-depleted mice. PMID- 1882131 TI - Developmental toxicity evaluation of tiron (sodium 4,5-dihydroxybenzene-1,3 disulfonate) in mice. AB - Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate), a chelating agent used in the treatment of experimental metal poisoning, was evaluated for developmental toxicity in pregnant Swiss mice. Tiron was administered intraperitoneally on gestational days 6 through 15 at doses of 0, 750, 1500, or 3000 mg/kg/day. Cesarean sections were performed on gestation day 18. All fetuses were examined for external, visceral, and skeletal malformations and variations. Treatment with Tiron resulted in maternal toxicity at 3000 mg/kg/day as evidenced by a high number of deaths, reduced body weight during gestation and increased relative liver and kidney weights. There were no significant differences between treated and control animals on the number of total implants, dead fetuses, or sex ratio. However, embryo fetotoxicity was evidenced at 3000 mg/kg/day by a significant increase in the number of resorptions per litter, and a significant decrease in the average fetal body weight. There were no significant changes in the incidence of abnormalities (expressed as total, individual, external, visceral, or skeletal). The no observable adverse effect level (NOAEL) for maternal and developmental toxicity was 1500 mg Tiron/kg/day. PMID- 1882132 TI - Plasma disappearance of creatinine as a renal function test in the dog. AB - The serum concentration of creatinine at 120 minutes (SC120) after intravenous injection of 88 mg kg-1 of creatinine, the plasma half-life (t1/2) and the plasma clearance of creatinine (PCC) were evaluated as renal function tests in 30 healthy adult dogs and six adult dogs with known or suspected renal disease. The mean SC120 in the normal dog was 0.31 +/- 0.08 mmol litre-1 and in the clinical cases 0.71 +/- 0.19 mmol litre-1. The correlation coefficients between SC120 and renal creatinine clearance (RCC) for the normal dogs and the clinical cases were 0.76 and -0.69, respectively. At 120 minutes after injection, 95 per cent of normal dogs would be predicted to have a serum creatinine concentration below 0.46 mmol litre-1. The mean plasma t1/2 of creatinine for the normal dogs was 107.7 +/- 17.96 minutes, while the clinical cases had a wide range of values (148.8 to 620.1 minutes). Plasma t1/2 of creatinine was correlated with RCC for both the normal dogs and the clinical cases (r = -0.55, r = -0.91, respectively). The mean PCC for the normal dogs was 7.42 +/- 2.22 ml min-1 kg-1 (range 4.95 to 13.28 ml min-1 kg-1). There was a good correlation between RCC and PCC (r = 0.7). The PCC for the clinical cases ranged from 0.76 to 3.37 ml min-1 kg-1. The correlation between RCC and PCC was significant (r = 0.91). Thus SC120, t1/2 and PCC may be useful methods of assessing renal function in dogs with renal impairment insufficient to cause azotaemia. PMID- 1882133 TI - Tuberculosis in domesticated red deer: comparison of purified protein derivative and the specific protein MPB70 for in vitro diagnosis. AB - The use of a Mycobacterium bovis-specific protein, mycobacterial protein bovis 70 (MPB70), was compared with complex, M bovis-derived purified protein derivative (bovine PPD), for its ability to improve the diagnostic precision of in vitro assays for tuberculosis in farmed deer. A combination of lymphocyte transformation and enzyme-linked immunosorbent assay (ELISA) was used to differentiate between specific M bovis reactivity and crossreactivity due to sensitisation with saprophytic mycobacteria such as Mycobacterium avium. In the lymphocyte transformation assay the response of mononuclear cells, from red deer, to MPB70 was found to be more specific, but less sensitive, as an indicator of infection by M bovis when compared with the complex antigen bovine PPD. When used in conjunction with bovine PPD alone, MPB70 was found to increase the specificity of the ELISA in diagnosing animals with disease. PMID- 1882134 TI - Use of a whole chromosomal probe for identification of Treponema hyodysenteriae. AB - A whole chromosomal DNA probe labelled with photobiotin was used in a dot blot hybridisation to identify DNA from isolates of Treponema hyodysenteriae, the aetiological agent of swine dysentery. The probe was evaluated using DNA from 13 isolates of T hyodysenteriae and 13 isolates of non-T hyodysenteriae spirochaetes recovered from pigs. The initial test had both a sensitivity and specificity of 92.3 per cent, although when it was repeated the specificity fell to 84.6 per cent. The test was helpful in distinguishing between T hyodysenteriae and other morphologically similar treponemes that are part of the normal flora in the large intestine of pigs. The probe could also be used to detect as little as 10 ng of purified DNA from T hyodysenteriae, or DNA from 2 x 10(6) bacterial cells lysed directly onto nitrocellulose. PMID- 1882136 TI - Characterisation of complex karyotype changes in a canine thyroid adenoma. AB - A 14-year-old German shepherd dog developed an alveolar adenoma of the thyroid. The cytogenetic evaluation of the tumour cells showed two ranges of chromosome numbers. Centric fusions 2/32, 5/26, 6/11, 8/11, 9/23 and 14/31 were G-band identified in this complex change of karyotype. PMID- 1882135 TI - Haematology and histopathology of seven-week-old broilers after early food restriction. AB - The haematology and histopathology of seven-week-old broilers were examined after periods of early food restriction, for six, 10 or 14 days from six days old. After several weeks on an ad libitum diet the birds failed to compensate for the weight lost during early food restriction. Immediately after the periods of food restriction, the birds demonstrated significantly increased heterophil/lymphocyte ratios, reduced eosinophils and slightly raised basophil counts. At seven weeks old, a significant reduction was seen in red and white blood cells and thrombocyte numbers together with significant increases in mean cell haemoglobin and mean cell volume. The haematological profile demonstrated a macrocytic normochromic anaemia caused possibly by a folic acid deficiency as a result of the food restriction. Histopathological lesions were seen in the heart, lungs and liver from birds on all diets but there were more lesions the longer the food had been restricted. Lung disease was more marked where there was inadequate ventilation. Cartilaginous and osseous lung nodules were significantly fewer after food restriction. It was postulated that the increase in pathological lesions in the food-restricted birds may be associated with a stress response. PMID- 1882137 TI - Distribution of penicillin-G and spiramycin to tissue cages and subcutaneous tissue fluid in calves. AB - Antibacterial drug concentrations in serum, tissue cage fluid (TCF) and subcutaneous tissue fluid (SF), sampled either by filter paper discs or by microcapillaries, were measured after single intramuscular injections of potassium penicillin-G (KPG), procaine penicillin-G (PPG) and spiramycin adipate in calves. Concentration-time curves had essentially similar profiles in serum and SF, but peak levels were lower and occurred later in SF. From approximately four hours after drug administration, penicillin-G levels in SF were similar to levels in serum after KPG as well as after PPG administration. Elimination half life (t1/2) of penicillin-G in serum was similar to t1/2 in SF after PPG administration but was longer in SF than in serum after KPG administration. Spiramycin concentrations were higher in SF than in serum and the t1/2 of spiramycin in SF was longer than in serum. For all three drugs, the t1/2 was longer in TCF than in serum and concentration-time curves in TCF were characterised by a slow rise and decline. The two methods of sampling SF, by filter paper discs and by microcapillaries, gave similar but not identical results. Penetration into SF and TCF, measured as the total area under curve ratio, was better for spiramycin than for penicillin-G, but the latter drug had a higher penetration ratio to TCF in the first 12 hours. PMID- 1882138 TI - Cross-reactivity between Actinobacillus pleuropneumoniae serotypes comparing different antigens and serological tests. AB - Several antigens were prepared from suspensions of reference strains of the 12 serotypes of Actinobacillus pleuropneumoniae (saline extract [SE], capsular extract [CE], whole cell suspension [WCS], boiled extract [BE], and autoclaved cell antigen [ACA]). The cross reactions between each antigen and the antisera against reference strains of the other 11 serotypes were compared by using the complement fixation test, ELISA and the indirect haemagglutination test. ACA produced the most cross reactions, which, in some serotypes, took place in all the antisera tested. BE produced fewer cross reactions, but these were more abundant than those obtained with SE, CE or WCS. The least cross reactivity occurred with SE in the indirect haemagglutination test. This test is, therefore, the most reliable method for serotyping field strains of A pleuropneumoniae. PMID- 1882139 TI - Fibronectin concentration in plasma of mares and neonatal foals. AB - Plasma fibronectin concentrations were measured in clinically healthy mares and their neonatal foals, using a modified human fibronectin competitive enzyme linked immunosorbent assay. Ranges of plasma fibronectin were established in clinically healthy horses, and the assay was reliable and reproducible. Plasma fibronectin concentrations were similar in mares and foals, both before and after colostrum ingestion. PMID- 1882140 TI - Serum cortisol changes in heifers induced by lipid X: a monosaccharide precursor in the biosynthesis of Gram-negative endotoxin. AB - An experiment was conducted to measure the changes in serum cortisol and luteinising hormone (LH) concentrations in heifers during the luteal phase of the oestrous cycle after the administration of lipid X and Gram-negative endotoxin. Nine heifers whose oestrous cycles were synchronised with prostaglandin F2 alpha were assigned at random on day 10 after the second prostaglandin injection to one of the following groups. Group 1 heifers (n = 3) received 5 micrograms kg-1 bodyweight of Escherichia coli endotoxin as an intrauterine infusion and one hour later received an intravenous injection of lipid X (5 micrograms kg-1 bodyweight). The treatment was reversed in group 2 heifers (n = 3), endotoxin was administered one hour after the lipid X treatment. Group 3 heifers (n = 3) received endotoxin infusion and lipid X treatment at the same time. Similar dosages and routes of administration were used in all the groups for lipid X and endotoxin treatments. Blood samples were collected once every 15 minutes for seven hours, beginning once hour before and six hours after the initial treatment. In group 1 heifers there was a fourfold increase in serum cortisol concentrations within 30 minutes after both the treatments (from 6.5 to 24.6 ng ml-1 and from 7.3 to 29.5 ng ml-1 respectively). In group 2 heifers the cortisol concentrations increased from the baseline concentrations of 7.2 to 33.2 ng ml-1 within 30 minutes after lipid X treatment and remained at 22.5 ng ml-1 during endotoxin treatment. There was a further increase in cortisol concentrations (28.9 ng ml-1) after the endotoxin treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882141 TI - Effect of cobalt deficiency in the pregnant ewe on reproductive performance and lamb viability. AB - Reproductive performance and lamb viability in cobalt sufficient and subclinically deficient ewes, and from ewes experiencing repletion from and depletion into cobalt deficiency, were investigated in two experiments. The sheep were fed a cobalt deficient ration and supplementation was by oral dose according to treatment. The treatments had a significant effect (P less than 0.001) on ewe serum vitamin B12 and methylmalonic acid concentrations. There were no significant effects on ewe liveweight, condition score or conception rate. Cobalt deficient ewes produced fewer lambs and had more stillbirths and neonatal mortalities than cobalt sufficient controls. Lambs from deficient ewes were slower to start suckling (P less than 0.05), had reduced concentrations of serum immunoglobulin G and zinc sulphate turbidity levels (P less than 0.05), and had lower serum vitamin B12 and higher methylmalonic acid concentrations (P less than 0.05), than lambs from cobalt sufficient dams. Cobalt supplementation in either the first or second half of pregnancy only did not fully alleviate these adverse effects. PMID- 1882142 TI - Physiological and pathological influences on sheep blood plasma amine oxidase: effect of pregnancy and experimental alloxan-induced diabetes mellitus. AB - A copper-containing amine oxidase is present in sheep blood plasma and has a high capacity to deaminate spermine and spermidine. The physiological function of this enzyme remains to be determined. Sheep blood plasma amine oxidase (SPAO) was measured by its ability to deaminate spermidine (700 microM) using a peroxidase linked colorimetric assay developed for microtitre plates. SPAO activity has been studied in a group of Welsh Mountain sheep with experimental alloxan-induced diabetes. This resulted in an increase in SPAO activity which reached a peak of 70 days after alloxan treatment (60 per cent increase). This change could be seen in both pregnant and non-pregnant diabetic sheep. In normal pregnant ewes, SPAO activity remained stable for the first 100 days of pregnancy but declined by 50 per cent in the last month of pregnancy. Together, these findings suggest that SPAO activity is controlled by hormonal influences. This sensitive and convenient assay method could provide clues as to the physiological significance of SPAO and may be a useful clinical chemical indicator in the sheep. PMID- 1882143 TI - Fat absorption in dogs with diabetes mellitus or hypothyroidism. AB - Quantitative fat absorption was studied in normal dogs and in dogs with hypothyroidism and diabetes mellitus. The serum triglyceride concentrations of diabetic and hypothyroid dogs were significantly higher at each sampling time than those of normal dogs. The fat absorption curve of hypothyroid dogs peaked at 180 minutes and though significantly raised was parallel to that of normal dogs whereas the fat absorption curve of diabetic dogs continued to rise up to 240 minutes. These results provide evidence for impaired plasma clearance of triglyceride in canine diabetes mellitus and hypothyroidism. PMID- 1882144 TI - Incidence of common DNA sequences in bovine and porcine Escherichia coli strains causing diarrhoea. AB - Seventeen bovine and 56 porcine Escherichia coli isolates from cases of diarrhoea and from healthy animals were examined for DNA sequences homologous to the genes for verocytotoxins (VT), enterotoxins and human enterohaemorrhagic E coli/enteropathogenic E coli (EHEC EPEC) sequences. VT-1 was the most common toxin among the bovine isolates and VT-2 the most common in the porcine isolates. No isolates had homologous sequences to enteropathogenic adherence factor, but 71.2 per cent hybridised to the DNA probe encoding specific EHEC sequences, and 95.9 per cent showed homology with a 23 kb DNA fragment common to EHEC and EPEC plasmids. PMID- 1882146 TI - Technique for continuous stride analysis of horses exercising on a treadmill. AB - A technique for continuous computerised recording and analysis of the stride of horses on a treadmill is described. Advantages of the system are low cost, the use of normal shoes and the calculation of stride parameters in real time. PMID- 1882147 TI - Cutaneous infection associated with Staphylococcus hyicus in cattle. AB - Forty-seven Staphylococcus hyicus strains, one each from 47 of 81 cattle examined, were isolated from cutaneous lesions on different parts of the body. Nineteen of the strains were isolated in pure culture and the rest were isolated in association with either other staphylococci or microfilariae or mange mites. Three out of 10 representative strains produced cutaneous lesions when inoculated intradermally into rabbits. PMID- 1882145 TI - Common epithelial tumours of the ovary in cows. AB - A morphological study of the epithelial tumours diagnosed during examination of 1489 cows slaughtered in Leon, Spain was carried out. Epithelial neoplasms were observed in four animals which represents an incidence of 0.27 per cent. So far as the authors are aware it is the first time that two serous papillary cystadenomas and one serous superficial papilloma have been described in cows. The fourth neoplasm was a mucinous cystadenoma. PMID- 1882148 TI - Suppression of lymphocyte blastogenesis by porcine interferon-alpha. AB - Peripheral blood lymphocytes (PBL) from five four-day-old and five six-week-old piglets were treated with 10 to 320 units of porcine interferon-alpha, and their blastogenic responses to phytohaemagglutinin or pokeweed mitogen were compared with those of control lymphocytes. There was significant inhibition of the blastogenic response to phytohaemagglutinin by 320 units of interferon-alpha, and of the response to pokeweed mitogen by 320 and 160 units of interferon-alpha. Porcine interferon-beta was cytotoxic to porcine PBL. The blastogenic response to pokeweed mitogen was significantly higher in PBL from the younger piglets. PMID- 1882149 TI - Information and education across the phases of cancer care. AB - Providing information to the cancer patient, is important but it is only one facet of patient education. Cancer patients also need to be taught new skills and shown new ways to cope. Patients who are not only informed, but are also educated and have more knowledge about their disease, are more likely to cooperate with treatment regimens and experience less stress and anxiety. One approach to identifying the content of cancer patient education is to focus on the various phases of cancer care. This approach provides a way for the patient and family to learn those aspects that are critical to coping with and adapting to the impact of the disease and its treatment. A number of researchers have begun to build the knowledge base important in identifying the appropriate educational content, methods for teaching, and approaches to evaluating teaching effectiveness. Future studies will continue to provide the scientific foundation for this most important aspect of cancer care. PMID- 1882150 TI - Selecting a systematic approach for educating hospitalized cancer patients. AB - Establishing cancer patient education programs for hospitalized cancer patients may follow a six-stage process that includes planning and strategy selection, selecting channels and materials, developing materials and pretesting, implementation, assessing effectiveness, and obtaining feedback to refine the program. The extent to which each of the stages is followed depends upon which stages are appropriate for the program and the consensus of hospital management. PMID- 1882151 TI - Evaluating written patient education materials. AB - Evaluation, the last component in the process of patient education, is the most frequently omitted step in producing informative material. Yet, it is essential that program/material evaluation be conducted to determine the impact and success or failure of the program or material. It is vital to be aware of this need and possess knowledge about types of evaluation and those areas that must be included to provide a comprehensive evaluation. PMID- 1882152 TI - Patient education: history, development, and current directions of the American Cancer Society and the National Cancer Institute. AB - With their unique perspectives in the identification, design, promotion, and evaluation of cancer patient education programs and services, the National Cancer Institute and the American Cancer Society have the abilities to meet a wide variety of cancer patient education needs. With federal support and connections to national organizations and the comprehensive and clinical cancer center networks, the National Cancer Institute has access to nationwide experts in medical care and the resources to develop, design, and promote quality, state-of the-art education programs. The American Cancer Society, with its strong volunteer community base, can pull together local expertise and collaborate with local organizations to meet the special needs of local population groups. In addition, the American Cancer Society volunteer committees have the flexibility to individualize programming and resources to answer specific patient/family education problems. As the number of people affected by cancer continues to raise, and as organizations realize the need to maximize their resources with collaborative efforts, the National Cancer Institute and the American Cancer Society are challenged to focus their energies on the patient education initiatives that build upon and combine their unique strengths. PMID- 1882153 TI - The whys of patient education. AB - The rationale for patient education is that patients and families have the right to be informed; that professional standards describe appropriate patient education; that health care organizations and the law require patient education; and patients, health care organizations, and that society benefit from the process. Patients with cancer benefit in terms of knowledge acquisition, enhanced self-care, reduced anxiety, enhanced self-concept and self-esteem, increased satisfaction with care, improved pain control, improved oral status, and reduced disruption in daily functioning. Health care organizations benefit in terms of quality services, reduced costs, and reduction in malpractice suits. Society benefits as patients with knowledge and skills maintain or resume functional status and return to school, work, or service activities. Nurses are key professionals in the coordination and delivery of patient education programs. They too have the opportunity to benefit from patient education through therapeutic alliances with patients and families that foster both personal and professional satisfaction. PMID- 1882154 TI - Theories used in patient/health education. AB - Patient and health education programs may need to use a multitheory approach to promote health behaviors such as cancer prevention and early detection practices and decrease negative responses such as anxiety, distress, pain, and use of damaging alternative treatments. Multiple intrapersonal, interpersonal, organizational, and community approaches are required. For example, a strategy for breast cancer education should be characterized by an understanding of the target population's attitudes and beliefs about breast cancer, communication of information, education regarding specific facts about breast health and breast cancer, social influence strategies to promote acceptance of the target behaviors, and organizational and community-based interventions to reach the widest audience. Nurses should design education programs that carefully integrate theories to obtain predicted result for the largest number of people for whom the results are desirable. Intervention strategies designed to alter the identified influential factors will have the most successful impact and optimal chance of attaining program goals. PMID- 1882155 TI - Brain function, learning styles, and cancer patient education. AB - As cancer care moves into the outpatient setting and hospital stays are shortened, patients and their family members are expected to take on tremendous responsibilities in providing their own self-care. At the same time, stress and anxiety about the diagnosis of cancer, the disease itself, and cancer therapy can effect learning. Information processing, learning styles, and learning barriers need to be considered when developing and implementing cancer education programs. PMID- 1882156 TI - [Respiratory risk of general surgery in adults]. AB - Disorders of ventilation and postoperative bronchial and pulmonary infections still create serious problems in general surgery. Three factors determine these complications: (1) the transient and usually resolutive repercussions of anaesthesia on ventilation; (2) the sometimes deep and prolonged alteration of lung function directly due to the surgical procedure, and (3) the patient's underlying condition. In practice, this last group of surgical patients can be divided into fragile subjects (elderly people, pregnant women), subjects at risk (smokers, malnourished or obese patients) and disabled subjects suffering from chronic obstructive or restrictive lung disease, asthma or heart disease. Preoperative clinical, radiological and, chiefly, functional evaluation leads to preventive measures. Preparation for surgery relies, to a great extent, on respiratory physiotherapy which, if needed, may be integrated in a pneumological therapeutic program. Combined with an efficient postoperative analgesia and with an optional anaesthesia technique, respiratory physiotherapy is essential to the prevention of respiratory complications in surgery. PMID- 1882157 TI - [Towards another diagnostic approach of peripheral pulmonary masses in pneumology: ultrasonically guided needle puncture]. AB - In a series of 50 patients with lung lesions touching the thoracic wall, percutaneous ultrasonically guided needle aspiration yielded a pathological diagnosis in 44 cases (sensitivity: 88%). The histological diagnosis of malignant lesion could be confirmed in 41 of these 44 patients. In this group of patients with neoplasia the diagnosis obtained by extemporaneous cytotology was compared with that obtained by lung biopsy: the diagnostic sensitivity of cytology proved to be higher than that of biopsy (86.36% and 65.90% respectively). Using the two methods concomitantly increased sensitivity up to 93.18%. A pathological diagnosis could be obtained in 3 out of the 6 patients in this series who had benign lesions. No bleeding was observed, and there was only one complication: a partial pneumothorax not requiring drainage which was detected by ultrasonography and confirmed by radiography. Thus, ultrasonically guided needle aspiration of lesions adjacent to the thoracic wall appears to be an efficient and reliable diagnostic method. Lack of irradiation, real-time guidance, low cost, high sensitivity and easily available equipment are as many reasons to prefer this method to other interventional radiology methods in patients with peripheral lung masses detectable by ultrasounds. PMID- 1882158 TI - [Randomized therapeutic trials of community-acquired lung diseases. Analysis of studies published between 1978 and 1988]. AB - The authors have evaluated the methodology of 21 randomized therapeutic trials concerning community acquired pneumonia. Only 33% of these trials were entirely devoted to community acquired pneumonia; the remainders included various respiratory infections. Only 8 trials were of the double-blind type. The presence of radiological opacity was mentioned as a criterion of inclusion in only 10 trials, and in 9 trials the diagnosis of pneumonia was not defined. The criterion of judgement, which separates success from failure, remained undefined in 6 trials. The number of patients analyzed was much lower than that of patients admitted because of exclusions for negative cultures or for isolation of a bacteria resistant to one of the antibiotics tested. Finally, in only 2 of the 21 trials it was concluded that an antibiotic was superior to the other(s). Clearly then, the quality of these randomized therapeutic trials needs to be improved by a better definition of their purpose and of the criteria of patients' admission, and by analysis of an intention to treat which is the nearest thing to the future use of the drug under study. PMID- 1882159 TI - [Interstitial pulmonary involvement of polymyositis and dermatomyositis. Apropos of 3 cases. Review of the literature]. AB - The authors report 3 new cases of myositis associated with pulmonary lesions that preceded or succeeded the muscular disorder. In one of these cases, which was particularly difficult to diagnose, the patient's serum was positive for the anti Jo1 antibody. These 3 cases have encouraged the authors to review the literature with particular attention to the diagnostic approach, the latest physiopathological data and the therapeutic basis of the "specific" pulmonary lesions associated with polymyositis and dermatomyositis. PMID- 1882160 TI - [Pneumocystis carinii pneumonia in patients with AIDS in the Congo]. AB - Forty-five bronchoalveolar lavages (BAL) were performed in Brazzaville in AIDS patients who did not expectorate acid- and alcohol-resistant bacilli (AARB). All patients presented with respiratory symptoms (cough, dyspnoea or chest pain), and all but 6 of them had abnormal radiography of the chest. Four cases of pneumocystosis were diagnosed (9%); 3 of these patients had interstitial pneumonia and dyspnoea. No AARB was found at microscopic examination of BAL which showed Pneumocyctis carinii; no culture on Lowehstein's medium could be made. The authors consider that the low prevalence of pneumocystosis in Africa, compared with industrial countries, is due to a smaller dissemination of the parasite in Africa rather than to immunodepression which is known to be more pronounced in AIDS patients from industrial countries. PMID- 1882161 TI - [Radiological case. An hydro-aeric lesion of the left basal lung]. PMID- 1882162 TI - [Endoscopic case. Endoscopic aspect of an intracavity space]. PMID- 1882163 TI - [Bilateral purulent pleurisy and spontaneous rupture of the esophagus (Boerhaave's syndrome). Apropos of a case]. AB - The authors report a case of bilateral purulent pleurisy consecutive to spontaneous rupture of the oesophagus (Boerhaave's syndrome). In such cases Mackler's triad, when complete, confirms the diagnosis. Standard radiography of the chest remains essential as it shows, at an early stage, the presence of mediastinal emphysema. PMID- 1882164 TI - [Muscular metastasis of pseudosarcomatous epidermoid bronchial cancer]. PMID- 1882165 TI - [Refractory hiccup after intrapleural injection of Corynebacterium parvum]. PMID- 1882166 TI - [Regression of hippocratic fingers during chemotherapy of bronchial cancer]. PMID- 1882167 TI - [Morphologic and morphometric aspects of the mammary gland of normal and oophorectomized rats treated with metoclopramide]. AB - The authors performed an optical microscope morphologic and morphometric study of the mammary glands of rats treated and untreated with metoclopramide during estrous and after ovariectomy. They observed that in the group of normal rats treated with the drug the glands were well developed and contained secretion in the lumen of their ducts and alveoli. In the group of rats submitted to ovariectomy and treated with metoclopramide, however, the glands were atrophied and had the same aspect of glands during estrous. These findings are in agreement with the morphometric study, which showed a statistically significant increase of parenchyma in the group of normal treated rats as compared to the other groups and, further, a higher number of alveoli with secretion. PMID- 1882169 TI - [Extensive trauma of the external ear: surgical management]. AB - Fifty nine patients with extensive traumatisms of the external ear, including 3 total amputations, 10 partial amputations with maintenance of reduced pedicle and 46 extensive lesions without further vascularization, have been attended in the Emergency Unit of Hospital das Clinicas at University of Sao Paulo Medical School from 1979 to 1989. Surgical behaviors performed in each case are described and explained in detail. The main purpose of the study was to show the outliving possibilities of the ear even in serious traumas and to emphasize the need of immediate repair of the ear in order to obtain a satisfactory result. PMID- 1882168 TI - [Grand multiparity: is it a high risk pregnancy?]. AB - PURPOSE OF THE STUDY: evaluate biological and medical characteristics of the grand multipara and her offspring in the neonatal period. TYPE OF STUDY: comparative and retrospective. SITE: Hospital of the Jundiai School of Medicine. PATIENTS: study group--134 grand multiparas; control group--100 primiparas. All patients were admitted to the Franco da Rocha Hospital, the maternity school of the Jundiai School of Medicine. INTERVENTION: analytical study. MEASURES AND RESULTS: hypertension, haemorrhage, twins, premature labor, pelvic location, and anemia were the complications seen in group 1. Cesarean section was indicated in the presence of a prior cesarean section, and fetal distress was the indication followed in group 2. Post partum damage to soft tissue was more prevalent in group 1. Premature labor and perinatal mortality were more frequent in group 1. CONCLUSION: The authors conclude that GMP were women with a high risk and, thus, they suggest adequate antenatal assistance as an important measure to decrease perinatal and maternal mortality. PMID- 1882170 TI - [Autologous fat transplantation in rats]. AB - The authors perform an experimental study in rats to demonstrate the integration of fat cells transplanted from the inguinal region to the dorsal region of the same animal. Histological studies were performed with the material removed and with the material injected. Final results show the transplanted fat cell integration after 360 days. PMID- 1882171 TI - [Cerebrovascular disorders]. PMID- 1882172 TI - [Juvenile rheumatoid arthritis: review and update]. AB - Major current clinical, laboratory, and etiopathogenic aspects of juvenile rheumatoid arthritis (JRA) are focused by this article. The authors make a comparison of data of their patients to those described in the literature. A retrospective clinicolaboratory study was performed of 130 patients with JRA followed in the Pediatric Rheumatology Department of the Division of Allergy, Rheumatology, and Clinical Immunology of the Service of Pediatrics of Escola Paulista de Medicina from 1982 to 1989. These patients (73 female and 57 male) were analyzed for the type and age of onset, clinical manifestations (articular and extraarticular), laboratory data, and prognosis. The findings of the authors are similar to those reported, with the exception of eye involvement (chronic iridocyclitis) and of the presence of the IgM rheumatoid factor (RF) and the antinuclear antibody (ANA), which were lower than those described by other authors. With respect to prognosis, the authors verified the greatest number of remissions (40%) with the pauciarticular type, whereas the polyarticular type presented the lowest number of remissions (27%). The two deaths occurred in the series were of children with the systemic type of the disease. Although etiology and the mechanism responsible for its release are not yet known, therefore, not allowing a definite type of treatment, experience gathered throughout the years has made it possible for physicians who attend to these patients not only to make an early diagnosis but also to resort to more efficient means of control. PMID- 1882173 TI - [Myasthenia gravis and pregnancy: review of the literature and report of 2 cases]. AB - Two cases of women with myasthenia gravis are presented. These women had three pregnancies followed by the authors, and description is made of clinical follow up, therapeutic complications, termination of pregnancy, puerperal and perinatal outcome. A review of the literature is made due to the rarity of this condition and emphasis is given to the specialized knowledge required to adequately manage these cases. Myasthenia gravis, when associated to pregnancy, presents aspects that make it a high risk disease, decompensations of myasthenia being more common. Aspects relative to diagnosis and therapy of myasthenia in pregnancy and in the newly-born are reviewed, and considerations about anesthesia in the myasthenic pregnant woman. PMID- 1882174 TI - [Chronic premature detachment of placenta]. AB - PURPOSE OF THE STUDY: to evidence the existence of chronic premature separation of the placenta. TYPE OF STUDY: retrospective. SITE: Hospital of the Jundiai School of Medicine. PATIENTS: four patients of the authors. INTERVENTIONS: without statistical treatment because this is not a comparative study. MEASUREMENTS AND RESULTS: chronic premature separation of the placenta, a classical asymptomatic or monosymptomatic disorder, can be detected by ultrasound and/or cardiotocography. Four cases seen among the authors' patients are presented, who were diagnosed by insidious evolution, discrete blood loss, and uterine excitability. Three of the patients were hypertensive. Diagnosis was established by amniocentesis, single or serial ultrasound, and cardiotocography. Newborns were premature, but the four of them survived. CONCLUSIONS: the authors conclude that the obstetric treatment depends on gestational age, fetal conditions, size of the clot, and intensity of blood losses. A conservative approach may be appropriate depending on fetal-maternal conditions. However, further studies are needed to devise more adequate approaches. PMID- 1882175 TI - [Acute appendicitis in pregnancy]. AB - A retrospective analysis of acute appendicitis during pregnancy in patients seen at the Surgical Service of Ribeirao Preto between December 1959 and December 1988 showed that out of 18,065 deliveries performed there were 7 cases of acute appendicitis (0.038%). Gestational age in which acute appendicitis developed varied from the 11th to the 27th week, the second trimester prevailing. Both in pregnant and in non-pregnant patients, clinical history of appendicitis was similar, except for a few cases in which the cecum, mobile as it is, caused localized pain in a more cranial position. Acute appendicitis during pregnancy showed a more aggressive evolution and despite a period lower than 24 hours, only two of our patients did not exhibit a purulent secretion in the abdomen during surgery. The two patients with a prolonged time of history had necrosed and perforated appendices. There was no maternal mortality. Among complications observed, wall abscess (14%), adynamic ileum (14%), and premature labor (28%) were the most important. Inhibition was not possible in one of the cases of premature labor, with the birth of a live fetus on the second postoperative day. The fetus died eventually. Other patients gave birth to live and timely fetuses. PMID- 1882176 TI - Correlation between leukocyte-associated plasma proteins and white cell differential count. AB - Prealbumin, albumin, orosomucoid (including the cellular variant orosomucoid2), alpha 1-antitrypsin, haptoglobin and transferrin were quantified in 107 cell samples from acute and chronic myeloid leukaemia, seven polycytaemia, seven normal blood marrow and 56 normal blood leukocytes by crossed immunoelectrophoresis. By statistical multivariate analyses, the individual plasma proteins and their combined protein patterns were correlated with the diagnoses and it was demonstrated that acute leukaemia cell samples contained significantly different protein patterns compared with the other diagnostic groups and normal controls. By comparison with the white blood cell differential count, in 78 samples of acute leukaemia, it was demonstrated that the protein patterns were significantly correlated with the specific cell types in the samples. In all, the differential counts accounted for about 29% of the variation in protein patterns. Alpha 1-antitrypsin was found significantly correlated with the myeloblasts and myelo-band cells. Orosomucoid2 and haptoglobin were significantly correlated with mature granulocytes and albumin was significantly correlated with lymphocytes. In some cell samples, after cytotoxic treatment of acute leukaemia, the granulocytes did not have orosomucoid2 despite normal morphology, suggesting defective maturation of these granulocytes. These results indicate that the mechanisms responsible for uptake of plasma proteins are highly specific for different cell types and in the case of myeloid cells specifically related to cell differentiation. PMID- 1882177 TI - A comparison of measurements of lean body mass derived by bioelectrical impedance, skinfold thickness and total body potassium. A study in obese and non obese normal subjects. AB - The measurement of body composition is an important part of metabolic and epidemiological research, but most currently available methods are complex and expensive. We have, therefore, compared measurements of fat mass (FM) and lean body mass (LBM), obtained using a commercially available bioelectrical impedance monitor (The Holtain Body Composition Monitor) (IMP), and by measuring skinfold thickness (SFT), with values obtained by measuring total body potassium (TBK). Twenty subjects, 10 with a body mass index (BMI) less than 30 (kg m-2), (non obese) and 10 with BMI greater than or equal to 30 (obese) took part in the study. There was a strongly significant linear relationship between LBM calculated from TBK and that calculated from impedance (IMP), in both non-obese and obese groups analysed separately (non-obese: r = 0.92; p less than 0.001 and obese: r = 0.92; p less than 0.001) and together (all: r = 0.89; p less than 0.001). LBM calculated from TBK was strongly linearly correlated with values derived from SFT for non-obese (r = 0.91; p less than 0.001) but not for obese subjects. Mean values of LBM of non-obese subjects derived by each method were not significantly different (TBK: 51.3 +/- 10.40 kg; IMP: 53.18 +/- 10.37 kg; SFT: 48.87 +/- 9.48 kg), but significant differences existed when the subjects were obese (TBK: 51.86 +/- 9.65 kg; IMP: 58.69 +/- 8.55 kg; SFT: 67.61 +/- 8.14 kg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882178 TI - Quality control does improve the performance of laboratory practice in primary health care. AB - Quality control surveys combined with teaching courses and expert consultations were offered to laboratories serving general practitioners in the county of Sor Trondelag, Norway. Fifty-one laboratories participated in the programme and the surveys during 1988-89. During the study period the number of laboratories having acceptable accuracy of their haemoglobin determination increased from approximately 80% to more than 90%. A similar increase was found also in precision where CV declined from 6.7% to approximately 2%. Additional positive effects were more close co-operation and more fruitful dialogues between the specialist laboratory and that of the general practitioners. The results offer promising perspectives to the control of laboratory performance in primary health care and the optimal use of laboratory tests. PMID- 1882179 TI - Increased levels of plasma homocysteine are associated with nephropathy, but not severe retinopathy in type 1 diabetes mellitus. AB - The reactive vascular-injuring amino acid homocysteine was measured in plasma samples from 79 well-characterized type 1 diabetic patients and 46 control subjects. Patients with proliferative retinopathy had higher homocysteine levels (15.0 +/- 6.3 mumols l-1; mean +/- SD, p less than 0.001; n = 42) than those with progressive retinopathy during a two-year period (10.4 +/- 1.6 mumols l-1; n = 12), no or minimal retinopathy (10.7 +/- 4.3 mumols l-1; n = 25), and the control subjects (11.0 +/- 3.4 mumols l-1). Within the group of patients with proliferative retinopathy increased homocysteine levels were confined to those patients that had serum creatinine levels greater than 115 mumols l-1 and/or an albumin:creatinine clearance ratio greater than or equal to 0.02 x 10(-3) (17.0 +/- 5.9 mumols l-1; n = 23), whereas those with no or only minimal nephropathy had levels (12.1 +/- 5.5 mumols l-1; n = 18) that were not different from the control group. We conclude that neither type 1 diabetes mellitus nor diabetic retinopathy per se is associated with increased plasma homocysteine levels. In contrast, homocysteine accumulates, probably owing to reduced glomerular filtration, in diabetic patients with advanced nephropathy. This suggests that homocysteine might contribute to the accelerated development of macroangiopathy seen especially in this subgroup of diabetic patients. PMID- 1882180 TI - Effect of diet therapy on maximum aerobic power in obese, hyperglycaemic men with recently diagnosed type 2 diabetes. AB - To find out the effect of correction of hyperglycaemia on maximum aerobic power and anaerobic threshold, we studied 40 middle-aged obese men with recently diagnosed type 2 diabetes before and after 3 months diet therapy. Respiratory gas exchange was measured during maximal incremental bicycle exercise test with breath-by-breath technique at rest, at anaerobic threshold and at peak exercise. As a whole group, the diabetic men reached higher work load after therapy (+9 +/- 3 W (mean +/- SEM), p less than 0.01). A weak inverse linear correlation was found between the changes in fasting blood glucose and in maximum oxygen uptake (r = -0.29, p less than 0.05). When the patients were divided into two groups according to the median values in the change in fasting blood glucose, only those men with more than 1 mmol l-1 decrease in fasting blood glucose improved maximum oxygen uptake (+124 +/- 55 ml min-1 or +6%, p less than 0.05). Oxygen uptake at anaerobic threshold did not change significantly. These results suggest that the correction of hyperglycaemia by diet therapy may improve maximal aerobic power in obese men with recently diagnosed type 2 diabetes. PMID- 1882181 TI - Protein kinase C subtypes in human neutrophils. AB - Protein kinase C from rat brain and human neutrophils was chromatographically separated on a hydroxylapatite column connected to a high-performance liquid chromatography (HPLC) system. Protein kinase C from rat brain was separated into three peaks (types I, II, and III). In contrast, only two types were obtained from human neutrophils matching type II and type III in brain. In cell membranes from unstimulated human neutrophils type III was predominant, but mainly type II was translocated to the membranes upon stimulation with phorbolmyristatacetate (PMA). Both types were equivalently activated by phosphatidylserine, diolein, and magnium and presented identical Km for ATP. PMID- 1882182 TI - Use of calcium-titrated sodium heparinate for ionized calcium determination on plasma and whole blood (heparinized blood sampler B-129 Radiometer). AB - We report modifications of ionized calcium as observed on specimens collected in a commercially available sampling device (Radiometer B-129). When the sampler is used as recommended, errors are non-significant around 1.25 mmol l-1. There is a +3% increase for low (0.75 mmol l-1) values and a -2% decrease for high (2.50 mmol l-1) values. Incomplete syringe-filling increases these errors. PMID- 1882183 TI - Reliability of the Reflotron system for cholesterol determination. PMID- 1882184 TI - Tyrosine phosphorylation in T-cell activation. PMID- 1882185 TI - Subclasses of IgG anticardiolipin antibodies in patients with systemic lupus erythematosus. AB - Antibodies directed to a co-factor associated with negatively charged phospholipids, such as cardiolipin, occur in patients with systemic lupus erythematosus (SLE), and possibly more often in those with venous or arterial thrombosis, thrombocytopenia or recurrent fetal loss. They are also found in patients without any of these manifestations and their biological effect, if any, might thus be related to their IgG subclass. To investigate this possibility, we determined anticardiolipin antibodies (ACA) by enzyme immunoassay (EIA) using monoclonal antibodies (MoAb) against human IgG subclasses. A net absorbance of x +3 SD of the value of 30 blood donors was taken as the cut-off point. The specificity of the assay was verified through inhibition experiments using cardiolipin micelles. Thirty-three patients with SLE were studied, all of whom had been shown to have ACA by a point dilution screening assay. IgG1 ACA were found in 85% of the patients, and ACA of the IgG2, IgG3 and IgG4 subclasses in 42%, 39% and 15%. There was a significant correlation between the presence of IgG3 ACA and of anti-DNA antibodies but none between subclass distribution and major clinical manifestations of SLE. PMID- 1882186 TI - High plasma fibronectin levels in multiple myeloma patients: possible mechanisms and clinical implications. AB - Fibronectin (FN) has been implicated in the formation of cryoprecipitates in rheumatic diseases and is present in tissues where, under pathological conditions, immune complexes are frequently deposited. We found elevated levels of FN in the plasma of 92% of multiple myeloma patients tested compared with a group of normal subjects, although the level of FN did not correlate with the level of the paraprotein. We then characterized the interacting fragments on both molecules and found that under physiological conditions of pH and ionic strength both heavy and light chain of all multiple myeloma and normal IgG showed affinity to FN; the active fragment on FN was found to be the aminoterminal heparin binding domain. These findings raise the possibility that FN might be implicated in some of the clinical symptoms of multiple myeloma. PMID- 1882187 TI - A murine monoclonal anti-idiotypic antibody detects a common idiotope on human, mouse and rabbit antibodies to allergen Lol p IV. AB - A syngeneic mouse monoclonal anti-idiotypic antibody (anti-Id), designated as B1/1, was generated against a monoclonal antibody (MoAb 91) specific for Ryegrass pollen allergen Lol p IV. This anti-Id recognized an idiotope (Id) that was also present on other monoclonal antibodies with the same specificity as MoAb 91. Observations that (i) the anti-Id inhibited the binding of MoAb 91 to Lol p IV and (ii) the Id-anti-Id interaction could be inhibited by Lol p IV indicated that the Id was located within or near the antigen combining site. These properties served to characterize B1/1 as an internal image anti-Id. Evidence that an immune response in different species to Lol p IV elicits the formation of antibodies which express a common Id was provided by the observations that (i) the Id-anti Id interactions could be inhibited by mouse, human and rabbit antisera to Lol p IV and (ii) the binding of these antisera to Lol p IV could be inhibited by the anti-Id. Interestingly, the internal image anti-Id B1/1 also recognized an Id on a monoclonal antibody which was directed to an epitope of Lol p IV, different from that recognized by MoAb 91. PMID- 1882188 TI - Localization of circulating immune complexes from patients with rheumatoid arthritis in murine spleen germinal centres. AB - In previous studies we have demonstrated high levels of rheumatoid factor (RF) and large-size (greater than 22S) circulating immune complexes (CIC) in the serum of rheumatoid arthritis (RA) patients with extra-articular disease. These findings were paralleled by a concurrent increase in the level of RF-associated cross-reactive idiotypes (CRI) and an apparent diversification of the RF repertoire detected in the serum of the same patients. In the present study we examine the ability of CICs to activate the complement system in vivo, and its possible influence on expanding the RF repertoire in RA patients with extra articular disease. Activation of complement by CICs is the key for germinal centre localization and long-term retention of such complexes on the surface of follicular dendritic cells (FDC), and so provides a source for the selection of cells with high affinity receptors for IgG and leads to the establishment of immunological memory. CICs containing different immunoglobulin isotypes and from different patients localized in mouse spleen germinal centres. However, intense localization was mainly seen for IgG-containing complexes from the serum of patients with large-size (greater than 22S) IgG-IgM RF complexes. The ability of these complexes to localize in mouse spleen germinal centres was related to activation of the complement system via the classical pathway in the patients' sera. Localization of IgG complexes was significantly (P less than 0.05) higher in sera from RA patients with extra-articular disease than those with articular disease alone. This study demonstrates the ability of large-size (greater than 22S) IgG-IgM RF complexes to activate complement, and suggests a possible role for such complexes in modulating the immune response to IgG in RA patients with extra-articular disease. PMID- 1882189 TI - Presence of NAP-1/IL-8 in synovial fluids indicates a possible pathogenic role in rheumatoid arthritis. AB - The synovial fluid in affected joints of rheumatoid arthritis (RA) patients contains many cells, in numbers strongly correlated with the severity of disease. As the disease worsens and the cell count increases, the polymorphonuclear leucocyte becomes the predominant cell type. Although the inflammatory cytokines interleukin 1 (IL-1) and tumour necrosis factor (TNF) have no direct neutrophil attractant activity, they are both potent inducers of interleukin 8 (IL-8) in a variety of cell types. Chemotactic attraction of neutrophils is a major activity of IL-8. Examination of a number of synovial fluids showed that significant levels of IL-8 are present in a high proportion of RA cases (10 out of 17), at concentrations directly related to the number of cells in the joint, and to circulating C-reactive protein (CRP) levels. The cytokine is present only at background levels in other diseases accompanied by arthritic manifestations, including systemic lupus erythematosus (SLE) and induced arthritis. The progressive joint destruction seen in all cases where high IL-8 levels were measured, coupled with the neutrophil-rich cell count and the strong correlation between concentration of IL-8 and both serum CRP and cellular influx into the joint, is strongly suggestive of a pathogenic role for IL-8 in RA. PMID- 1882190 TI - Inhibition of neutrophil chemotaxis by elastase-generated IgG fragments. AB - IgG1 is cleaved in vitro by granulocyte elastase into Fc and Fab fragments. The elastase-specific Fc fragment has been previously detected in vivo. Biological activity of the fragments has been described in modulating neutrophil oxidative metabolism and enzyme release. To investigate further effects granulocyte chemotaxis (CT) was tested. The CT was assayed in Boyden chambers and the chemotactic index (CI) was calculated which represents the mean distance travelled by the activated cells. Stimulation of leucocyte CT by casein, activated serum and FMLP gives maximal values of delta CI = 46.7, 26.4 and 7.2 microns, respectively. Native IgG1 and the elastase-produced IgG fragments do not stimulate leucocyte CT. FMLP-stimulated CT is specifically inhibited by the elastase-produced Fc fragments. Addition of 7 nmol Fc to stimulus concentrations of 16 to 125 nM FMLP results in total inhibition of chemotaxis demonstrated by CI values which are lower than those for unstimulated cells. The inhibition of CT is concentration dependent in the range of 2 to 7 nmol Fc/10(6) PMN. Number and affinity of FMLP receptors are not influenced by Fc fragments, so Fc binds neither to FMLP nor the FMLP receptor. CT stimulated by casein shows a large portion of chemokinesis. Only at suboptimal casein concentrations do Fc and IgG have an inhibitory effect on CT (0.63 mg casein/ml, 10 nmol peptide/10(6) PMN). C5a-stimulated CT is not influenced by IgG or IgG fragments which indicates that the samples are not cytotoxic. So the FMLP and casein-stimulated CT is specifically inhibited by the elastase-produced Fc fragments in a low concentration range. PMID- 1882191 TI - Idiotypic replica of an anti-human tumour-associated antigen monoclonal antibody. DNA sequence comparison between Ab1 and Ab3. AB - 2G-3 is an anti-anti-idiotypic MoAb (Ab3) obtained upon immunization with a monoclonal Ab2 (A3B10), which behaves as the 'internal image' of CaMBr1, a saccharide epitope defined by MoAb MBr1 (Ab1). CaMBr1 is expressed on glycoconjugates of the human mammary carcinoma cell line MCF-7 and on normal and neoplastic mammary gland epithelial cells. Ab1 and Ab3, although exhibiting, in many respects, superimposable paratopic and idiotopic specificities, show a non identical fine immunoreactivity, since 2G-3 has a preferential reactivity with the saccharidic epitope mounted on glycoproteins, while MBr1 reacts with both glycoproteins and glycolipids. V-region sequence analysis has shown that: (i) the VK genes employed belong to different families (VK1 and VK10); (ii) the JK2 segment is shared by the two L chains (thus a high degree of homology is observed between VK CDR3s); (iii) the VH genes employed derive from the same family VHIIB/J558 (but show CDR homology only in CDR2); (iv) different JH region genes are employed. These data, together with the comparison of deduced secondary structure parameters, give further evidence for the possible production of similar combining sites using different VH and VL germ-line genes. PMID- 1882192 TI - Fungemia in a university hospital 1984-1988. Clinical and mycological characteristics. AB - 118 episodes of fungemia occurring at Rigshospitalet, Copenhagen, between 1984 and 1988 were reviewed retrospectively. Underlying diseases in the patients were dominated by malignancies, primarily hematological disorders, and intraabdominal diseases requiring major abdominal surgery. Predisposing factors identified in the patients were ongoing antibacterial chemotherapy (83%), central venous catheters (72%), major abdominal surgery (39%), and neutropenia (32%). 120 fungal strains were isolated, of which 88 (73%) were Candida albicans, 23 strains representing 8 other Candida species were also isolated, as were 9 strains belonging to 7 other fungal genera. There were only 5 strains resistant to 5 fluorocytosine (MICs greater than or equal to 25 mg/l), and no strain was resistant to amphotericin B. Treatment with antifungal agents was given in 78 patients, generally a combination of amphotericin B and 5-fluorocytosine. In 14 patients (all non-hematological) the only treatment was removal of a permanent central venous catheter. The outcome was poor in patients with hematological disorders (mortality 76%), whereas patients with malignant and non-malignant intraabdominal diseases had a mortality of 35%. All patients with a permanent central venous catheter as the only risk factor recovered rapidly after removal of the catheter. PMID- 1882193 TI - Varicella-zoster infection in adults with cystic fibrosis: role of acyclovir. AB - Of 159 adult patients with cystic fibrosis, 5 were documented to have varicella zoster infection that resulted in an infective pulmonary exacerbation that required intravenous acyclovir and additional antibiotic treatment. Stable serial pulmonary function values were observed over a 1-year period in 4 patients and no complications resulted from treatment. Early treatment with acyclovir in combination with appropriate antibiotics may prevent pulmonary deterioration in adult patients with cystic fibrosis who develop varicella-zoster infection. PMID- 1882195 TI - Chlamydia pneumoniae infections in Norway 1981-87 earlier diagnosed as ornithosis. AB - Ornithosis has been a notifiable disease in Norway since 1957. During an outbreak of respiratory disease in 1981-82, described as ornithosis, contact with birds was stated in only 50% of the cases, suggesting that the infection was spread by interhuman transmission. A similar outbreak occurred in the western part of Norway in 1987. Serum specimens from altogether 260 patients, collected during the outbreaks in 1981-82 and in 1987, were investigated for antibodies against Chlamydia pneumoniae (strain TWAR). Evidence of recent infection with C. pneumoniae was found in 67.7% of the cases. The results indicate that the increased incidence of ornithosis in 1981-82 and in 1987 was due mainly to C. pneumoniae infections. PMID- 1882194 TI - Short course of aerosol pentamidine as treatment of Pneumocystis carinii pneumonia in AIDS. AB - Since July 1987, 20 HIV-positive patients with Pneumocystis carinii pneumonia (PCP) admitted to the Department of Infectious Diseases, Malmo General Hospital, Sweden have been treated with 10 consecutive days of aerosol pentamidine as sole antimicrobial therapy in a prospective open non-controlled trial. 16 patients (80%) responded to 10 days of 400 mg aerosol pentamidine daily. One patient responded after a prolonged treatment, one patient received simultaneous trimethoprim-sulfamethoxazole due to lack of improvement during aerosol therapy. Two patients died 26 and 41 days after initiation of treatment. No systemic side effects occurred. In conclusion, we found that 10 days of aerosol pentamidine may be a safe and effective treatment of PCP. Controlled studies are needed. PMID- 1882196 TI - Chlamydia pneumoniae respiratory tract infection: the interpretation of high titres in the complement fixation test. AB - Sera from 5 acute respiratory disease patients from Northern Norway presenting with high chlamydia complement fixation (CF) titres, were analyzed for Chlamydia pneumoniae-specific IgG and IgM in a micro-immunofluorescence (micro-IF) test that included antigens from the prototype strain TW 183, and a Norwegian isolate, FML 10. The patients were confirmed to have had C. pneumoniae infection based on serologic findings. This establishes the clinical significance of early CF results in this geographical area. However, different micro-IF titres against the 2 C. pneumoniae isolates tested suggest antigenic variability among the species. PMID- 1882197 TI - Evaluation of coagulase-negative staphylococci in blood cultures. A prospective clinical and microbiological study. AB - Coagulase-negative staphylococci (CNS) are the commonest microorganisms in blood cultures, and sorting out patients with CNS septicemia from sample contamination a persistent problem. We prospectively evaluated 73 patients with CNS-positive blood cultures during 1 year and analysed the corresponding 122 isolates in order to determine the rate of septicemia and define the role of microbiological markers of identity such as plasmid profile for that purpose. Three patients had true septicemia, all of them with implanted foreign devices. The plasmid analysis, being the most reliable identity marker, had its greatest implication in reducing the intermediate group of patients clinically suspected of septicemia from 12 to 4. Strict clinical criteria and serial blood cultures are most important in sorting out patients with CNS septicemia from cases of sample contamination. In high risk patients--critically ill with implanted foreign devices--plasmid analysis or other reliable markers of identity are of great additional value. PMID- 1882198 TI - Antibiotic susceptibility of coagulase-negative staphylococcal blood isolates with special reference to adherent, slime-producing Staphylococcus epidermidis strains. AB - The epidemiologic relationship between slime-producing coagulase-negative staphylococci and antibiotic resistance was evaluated by analyzing the in vitro susceptibility of 278 blood isolates to 10 different antimicrobial agents. The strain collection consisted of 60 coagulase-negative staphylococcal septicemia isolates, recovered from at least 2 successive blood cultures from 59 septicemia patients and 218 single blood isolates defined as insignificant. When the slime producing Staphylococcus epidermidis isolates were compared with all non-slime producing S. epidermidis isolates, the slime-producing isolates exhibited higher MIC50 and/or MIC90 values than the non-slime-producing isolates, and were also more commonly resistant against many of the antimicrobials tested. The association between slime production and resistance against tobramycin, gentamicin and rifampicin was statistically significant (p less than 0.05). A similar finding was observed among the S. epidermidis septicemia isolates when they were analyzed separately from the single (suspected blood contaminant) S. epidermidis isolates. Further characterization of the septicemia isolates revealed that the positive correlation between slime production and antibiotic resistance reflected, to some extent, multiresistance of 1 epidemic slime producing S. epidermidis strain. No difference in resistance was observed between the slime-producing and non-slime-producing single S. epidermidis blood isolates. PMID- 1882199 TI - Antibiotic susceptibility of invasive Haemophilus influenzae type b isolates in Denmark in 1988 and 1989. AB - A system for surveillance of invasive Haemophilus influenzae type b infections in Denmark yielded 135 strains isolated from blood or cerebrospinal fluid from August 1988 through December 1989. The susceptibility of the strains to 7 antibiotics was investigated by an agar dilution method. Ceftriaxone was found to be the most active drug followed by cefotaxime, ceftazidime, rifampicin, ampicillin, cefuroxime, and chloramphenicol. Except for ampicillin the MICs for the individual antibiotics were similar. Seven strains (5.2%), which all produced beta-lactamase, were resistant to ampicillin. Since H. influenzae type b meningitis in otherwise healthy individuals almost exclusively occurs in children aged 2 months to 4 years, a third generation cephalosporin such as ceftriaxone or cefotaxime may be considered the drug of choice for initial therapy of meningitis in this age group. PMID- 1882200 TI - Antimicrobial therapy of septicemic patients in intensive care units before and after blood culture reporting. AB - 68 cases of positive blood cultures from 54 intensive care unit (ICU) patients were analyzed retrospectively. The empiric antimicrobial therapy was correct in 65% of the cases as judged by the species and sensitivity of the blood culture isolate. After initial Gram-staining results were known, coverage increased to 77%. After the final blood culture results the coverage was still only 81%. The bacteremia-related mortality was 13%. Although there was no significant difference between the occurrence of bacteremia-related and non-bacteremia related deaths either in patients with correct or non-optimal empiric treatment, this study emphasizes the need for better utilization of culture reporting. A considerable part of the final blood culture results went unnoticed by the ICU physicians which stresses the importance of good communication between the laboratory and wards. PMID- 1882201 TI - Septicaemia caused by unusual Campylobacter species (C. laridis and C. mucosalis). AB - Two cases of campylobacter septicaemia are described. The first, caused by Campylobacter laridis was associated with gastroenteritis and occurred in a healthy individual. In the second case, a catalase negative species, C. mucosalis was isolated from blood in an immunocompromised patient with symptoms of pneumonia. Both campylobacter strains grew faintly under the routine culture conditions used. Improved diagnostic procedures for Campylobacter species may thus be warranted. PMID- 1882202 TI - Cure of zygomycosis caused by a lipase-producing Rhizopus rhizopodiformis strain in a renal transplant patient. AB - A 40-year-old man with renal failure due to membranous glomerulonephritis received a cadaveric renal transplant and immunosuppressive therapy with cyclosporine, azathioprine and steroids. Initially the transplantation was successful. 12 days after the transplantation, however, serous secretion appeared in the wound. Later, black necrosis was seen. Fungal culture showed growth of a zygomycete species. Rhizopus rhizopodiformis, with high in-vitro resistance to amphotericin B, flucytosine, fluconazole, ketoconazole and itraconazole. The MIC value for the allylamine derivative SF86-327 (Exoderil) was 1.6 micrograms/ml. Microscopic examination of sections from a surgical revision showed necrosis of the fat tissue and massive hyphal invasion of the perirenal fat, which contained semi-crystalline material anisotropic as seen in polarized light and characteristically staining with rubeanic acid. These histological data indicate a lipase-induced in-vivo splitting of lipids into fatty acids. In-vitro R. rhizopodiformis showed very high extracellular lipase production. 11 days after initiation of amphotericin B therapy cultures and sections remained positive for rhizopus. Amphotericin B was therefore supplemented with Exoderil orally, cyclosporine and steroids were maintained, and azathioprine was discontinued. The wound granulated, shrank, and healed completely in 10 weeks. PMID- 1882203 TI - Endemic prevalence of Chlamydia pneumoniae in subjectively healthy persons. AB - Subjectively healthy persons were investigated for the presence of Chlamydia pneumoniae (TWAR) with throat cultures using the HL (human lung) cell line. C. pneumoniae was isolated from 11/234 investigated persons. PMID- 1882204 TI - Blastocystis hominis may be a potential cause of intestinal disease. AB - Blastocystis hominis is a common inhabitant of the human bowel. It is now increasingly recognized as a potential cause of diarrhea. This article presents 12 cases of prolonged or recurrent diarrhea associated with B. hominis found in a large number. No other intestinal parasites were recognized. All patients responded to metronidazole. This report confirms that B. hominis may be a cause of intestinal disease. PMID- 1882205 TI - Paracoccidioidomycosis and AIDS. PMID- 1882206 TI - Mononeuritis multiplex in leptospirosis. PMID- 1882207 TI - Phenomenology or physicalism? AB - The author uses a segment of the National Plan for Schizophrenia Research as a representation of the current academia-driven philosophical trend of "Biological Psychiatry." A criticism of the underlying assumptions of this school of thought is offered, including the doctrines of physicalism, essentialism, and logical positivism. Quotations from authoritative sources are provided to indicate that modern biology rests on entirely different assumptions and that different models and scientific methods are in order in psychiatry to get in step with the progress in contemporary science. PMID- 1882208 TI - Seasonality of birth of future schizophrenics and seasonality of depressive episodes. PMID- 1882209 TI - Update on the clinical efficacy and side effects of clozapine. AB - Clozapine (CLOZ) is an atypical antipsychotic drug being used with increasing frequency throughout the world and has recently been commercially marketed in the United States. Its unique properties make it a promising but challenging drug to use in the treatment of schizophrenia. In order to use CLOZ most effectively and efficiently, clinicians must be aware of its potential benefits and risks. This report is a review and critical evaluation of current knowledge regarding the clinical efficacy and side effects of CLOZ. Although CLOZ has proven to be effective in some treatment-refractory schizophrenic patients and to produce relatively few extrapyramidal side effects compared to classical neuroleptic drugs, several issues require further investigation including what defines neuroleptic intolerance, the optimal dose range, and the appropriate duration of a CLOZ treatment trial. Similarly, studies are needed to determine what role CLOZ should have in the treatment of patients with predominantly negative symptoms and those patients who are only partially responsive to standard neuroleptics. In addition, important questions remain as to what other conditions might be indications for CLOZ, for example, schizoaffective disorder, affective psychoses, and idiopathic Parkinson's disease. PMID- 1882210 TI - First person account: the schizophrenic inside. PMID- 1882211 TI - [Fractures due to bony insufficiency of the sacrum]. AB - Six cases of insufficiency fracture of the sacrum were diagnosed in the Rheumatic Diseases Division of the CHUV during 1990. They show that this recently described entity is frequent. Present knowledge of the clinical course, predisposing factors, radiological findings and treatment is reviewed. This diagnosis should be considered in all cases of lower back pain occurring in postmenopausal women. Awareness of this entity should make it possible to avoid unnecessary invasive investigations. PMID- 1882212 TI - [Comparison of a calorie-defined diet with the conventional exchange diet in Type 2 diabetes mellitus]. AB - Meal planning using food exchange lists is problematic for many elderly type 2 diabetic subjects because the system is too complicated and too rigid regarding the daily meals. In addition, exchange lists are calorically imprecise. 12 non insulin-dependent diabetic subjects agreed to participate in the present study (6 male, 6 female; age 40-82 years, weight 80 +/- 6 kg; HbA1c 7.3 +/- 0.3%); they received sequentially in randomized order either a diet using exchange lists, or a diet defined by total amount of allowed daily calories ("calorie diet"), both containing approx. 25 calories/kg ideal body weight/day, each for 8 weeks. The "exchange lists" mainly contained foods which were defined according to their content in carbohydrates (including bread exchanges, fruit exchanges, milk exchanges, vegetable exchanges). With the "calorie diet" the patients were relatively free during the day, the only rule being that they were allowed to consume a certain amount of calories per day, using a "calorie ruler". The results demonstrated that body weight decreased similarly during both diet periods (2.0 +/- 0.8 kg during the exchange list diet; 2.5 +/- 0.9 kg during the "calorie diet"). Fasting blood glucose concentration decreased during the "calorie diet" by 7% (p less than 0.05; fasting blood glucose at the end of the "calorie diet" was lower than after the exchange list diet (p less than 0.016). Serum lipoproteins were similar after both diet periods. 10/12 patients preferred the "calorie diet" because of its simplicity and flexibility. It allowed consumption of instant food which was calorically defined but difficult to convert into the exchange system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882213 TI - [Accidental hypothermia in Switzerland (1980-1987)--case reports and prognostic factors]. AB - This retrospective study comprises 234 cases of accidental hypothermia (core temperature less than 35 degrees C) hospitalized in 95 Swiss clinics between 1980 and 1987. The most frequent accidents were alpine (n = 78) in origin, followed by cold exposure after injuries (n = 63) and suicide attempts (n = 43). Hypothermia was induced by cold air in 129 cases and by water in 47 cases. Patients were divided evenly between the degree of hypothermia: 75 mild (32-35 degrees C), 79 moderate (28-32 degrees C) and 66 severe (less than 28 degrees C). Among the survivors the coldest patient had a core temperature of 17.5 degrees C and the longest cardiac arrest with a favourable outcome lasted 4.75 hours. Out of the 234 patients 68 died (29%). We assessed all variables relative to outcome, in particular the mechanism of the accident, the mode of cooling, temperature, circulation, age and sex, underlying diseases, rewarming methods, medication and complications during the hospital course. All variables were tested in two multiple regression analysis models (retrospective model n = 181: prospective model n = 128) with regard to significance (p less than 0.05) and survival. Results are expressed with ODD's ratios (OR). The negative survival factors are asphyxia (OR 30), invasive rewarming methods (OR 20), slow rate of cooling (OR 10), asystole on arrival (OR 9), pulmonary edema or ARDS during hospitalization (OR 8), elevated serum potassium (OR 2/mmol/l) and age (OR 1.03/year). The positive survival factors are rapid cooling rate (OR 10), presence of ventricular fibrillation in cardiac arrest patients (OR 9) and presence of narcotics and/or alcohol during hypothermia (OR 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882214 TI - [Why do cancer patients use alternative medicine?]. AB - 160 patients (53.3%) replied to an anonymous questionnaire distributed to 300 consecutive patients of our Outpatient Oncology Clinic. 83 patients (53%) mentioned some experience of one or more alternative methods of cancer treatment. Most often cited were various herbal teas (35 instances), beetroot juice (16), Vogel plant extracts (15), laying-on of hands (14), homeopathic medicine (13), the mistletoe extract Iscador (13), magnetopathy (12), various diets (10), acupuncture (10) and psychological methods (9). Resort to alternative methods of treatment correlated significantly with lower age (51.5 years vs 59.8 years, p = 0.001). The reasons for using alternative medicine were the desire to do everything possible to regain health (49), to use one's psychological forces as well (35), reports of successful cancer cures (28), desire for a holistic approach (23), hope of "softer" medicine with less severe side effects (18) and, in 7 cases only, disappointment with conventional university medicine. The major source of information was relatives and friends, not the mass media. The physician should be aware of the locally available alternative medicine options and be able to advise his patients accordingly. He should also recognize and give due consideration to the patient's underlying desire for better control of his disease and a more holistic approach to care. PMID- 1882215 TI - [Cheek and neck swellings. Their clinical picture, diagnosis and differential diagnosis]. PMID- 1882216 TI - [HIV infection. The prognostic value of buccal candidiasis and hairy leukoplakia in HIV infection. A critical and comparative analysis]. PMID- 1882217 TI - [The legal position of the dentist]. PMID- 1882218 TI - [School dental care in the Canton of Tessin]. PMID- 1882219 TI - [A common stance of European dentists requested]. PMID- 1882220 TI - [Sulcus fluid in periodontal diagnosis. A review]. AB - In the present review, the composition of the gingival crevicular fluid (GCF) as well as its important role in the diagnosis of periodontal disease have been discussed. Furthermore, the different sampling methods and the subsequent analytical procedures have been described. Some of the GCF-components, such as elastase, prostaglandin, arylsulphatase and beta-glucuronidase, are examined for their use as suitable markers of future disease activity. At the present time, the interest of research is focussing on the host-parasite interaction, the prediction of disease activity, and the identification of risk groups of patients. Therefore, GCF is considered a valuable research subject and a possible diagnostic marker. PMID- 1882221 TI - [The effect of cavity finishing on the initial sealing capacity of amalgam fillings in vitro]. AB - The effect of different cavity finishing methods on in-vitro microleakage of two amalgams (Amalcap non gamma 2 SAS, Tytin) was investigated by the dye penetration method. Amalcap non gamma 2 SAS demonstrated better sealing properties than Tytin. The highest degree of microleakage was observed when the cavities prepared with a diamond coated bur (mean particle size 80 microns) were left unfinished. The degree of marginal leakage in Class-I cavities was reduced by finishing their walls with tungsten carbide or diamond coated finishing burs. Cervical Class-II cavity walls finished with a tungsten carbide or a diamond coated finishing bur demonstrated lower marginal leakage than cervical walls finished with a gingival margin trimmer. Finishing of proximal Class-II cavity walls with tungsten carbide or diamond coated finishing burs followed by removal of the remaining enamel overhangs with a diamond coated file (Cavishape) resulted in a lower degree of dye penetration than finishing proximal walls with a proximal margin trimmer. The results indicate that Class-II cavities with minimal extension of the proximal walls can be effectively finished without using hand instruments. PMID- 1882222 TI - [The determination of caries risk in schoolchildren based on microbiological chemical analyses of the saliva and on the clinical dental status]. AB - In a feasibility study for the determination of the caries risk in children by whole school class, the number of the colony forming units of mutans streptococci and lactobacilli in the stimulated saliva, the buffer capacity of the saliva and some chosen clinical indicators of increased caries risk were determined and evaluated in 103 schoolchildren (7 to 10 years old) in the city of Zurich. Mutans streptococci in the saliva were found in 73% of the children and lactobacilli in 77%. In 11% of the children, neither of the microorganisms were found. Sixty three percent of the children showed a strong buffer capacity of the saliva and 12% a small one. On the basis of these results and some selected clinical factors, 30% of the children were classified as patients with a high caries risk and are now following an intensive prophylaxis program. PMID- 1882223 TI - [Primary malignant melanoma of the oral cavity: a case report and review]. AB - The oral cavity is a rare location for the development of primary malignant melanoma. Two cases of malignant melanoma of the superior alveolar process are described. The necessity of an early recognition and of clarification concerning the differential diagnosis of oral pigmentation as well as the treatment are discussed, together with a review of the literature. PMID- 1882224 TI - Proteins 2, malaria 0. PMID- 1882225 TI - Birds of a fever. PMID- 1882226 TI - Opium, cocaine and marijuana in American history. PMID- 1882227 TI - Lead in sweat and its relationship to salivary and urinary levels in normal healthy subjects. AB - Sweat was collected from the arms of 24 normal healthy subjects while they sat in a hot chamber. Blood, urine and saliva samples were also collected. These were analyzed for lead by atomic absorption spectrophotometry. Sweat lead levels recorded in this study are lower than those previously reported. Subjects with mean blood lead levels of 8.62 micrograms dl-1 (range 6-13.6) had mean sweat levels of 5.2 micrograms l-1 (range 1.5-13.0), approximately 25% of their urinary levels. Although salivary lead levels with a mean of 4.8 micrograms l-1 (range 2.5-10) are comparable to sweat levels, their relationship to blood lead levels is poor (r = -0.186 compared with r values of 0.7208 and 0.234 for sweat and urinary levels, respectively). PMID- 1882228 TI - Sweat lead levels in persons with high blood lead levels: lead in sweat of lead workers in the tropics. AB - Samples of blood, sweat and urine were collected from eight control subjects and 19 lead workers in a battery manufacturing factory in the tropics. Sweat samples were collected while workers cycled on a bicycle ergometer at room temperature (27-31 degrees C). All samples were analysed by atomic absorption spectrophotometry. Workers with blood lead levels of 13-36 micrograms dl-1 had sweat levels of 72-256 micrograms l-1 and urinary levels of 28-288 micrograms/g creatinine, while controls had levels of 9-12.2 micrograms dl-1, 9-30 micrograms l-1 and 9-19.6 microgram/g creatinine, respectively. Estimations of sweat lead in lead workers can be masked by skin contamination. PMID- 1882229 TI - Mutagenicity of the components of ozonated humic substance. AB - Eight components of humic substances were ozonated. Mutagenic activity was found with TA100 with and without S9 mix for all ozonated components. Ozonated products of p-hydroxybenzaldehyde were separated into five fractions by silica gel chromatography and each fraction subjected to mutagenicity assay. Mutagenic activity was found in the chloroform and chloroform-acetone (1:1) fractions. The compounds in these fractions were identified, and aldehydes such as formaldehyde, acetaldehyde, glyoxal, glyoxylic acid and methyl glyoxal were found to be mutagenic. Mutagenic compounds are present in the polar fraction. PMID- 1882230 TI - Mutagenicity of ozonation and chlorination products from p-hydroxybenzaldehyde. AB - p-Hydroxybenzaldehyde, a component of soil humic substances, was ozonated and chlorinated. The ether extract and the residue were subjected to the Ames assay; mutagenic activities were identified. The non-ionic resin CSP800 and the anion exchange resin CHPA25 were used for separation of mutagenic compounds. The compounds in the water layer were not adsorbed on CSP800 or CHPA25 and exhibited strong mutagenic activity. Mutagenic activity was reduced as the added chlorine was increased. Ether extracts were analyzed by gas chromatography-mass spectrometry (GC-MS) and chloral, 1,3-dichloro-2-propanone, 1,2,3-trichloro-1 propene, tetrachloroethylene and 1,1,1,3,3-pentachloro-2-propanone were identified as mutagenic compounds. PMID- 1882231 TI - The quality of groundwater in Bahrain. AB - The quality of groundwater and house tap water throughout the State of Bahrain has been investigated with respect to pH, salinity, conductivity, bicarbonate, chloride, sulfate, sodium, potassium, magnesium, calcium, nitrite, nitrate, ammonia and phosphate. Groundwater showed elevated levels for salinity, chloride, sulfate, sodium and magnesium, with ranges of 1.40-9.30 ppt, and 110-4407, 239 1385, 247-2165, and 36-313 mg l-1, respectively. These values increased from western Bahrain reaching maximum values along the southeastern coastal zone. Nitrate concentration ranged from 1.3 to 23.3 mg l-1 with an average value of 4.4 mg l-1. The results of the study indicate deterioration of groundwater in localized areas. In the case of tap water, the observed ranges for salinity, chloride and sodium were 0.7-1.5 ppt, and 280-750 and 140-400 mg l-1, respectively. The quality of tap water was assessed by comparing values with WHO guidelines. PMID- 1882232 TI - Monitoring of cadmium, copper, lead and zinc status in young children using toenails: comparison with scalp hair. AB - Cadmium, copper, lead and zinc concentrations were determined (atomic absorption spectrometry) in the proximal end of scalp hair (n = 474) and in toenail clippings (n = 461) of children, aged 3-7 years, living in an industrialized and in a rural area of the Federal Republic of Germany. With the exception of Zn in hair, levels of the elements were log-normally distributed. Data are presented as geometric means. Toenail Cd and Pb levels were much higher than those in hair (Cd, 457 vs 90 ng g-1; Pb, 8.5 vs 2.7 micrograms g-1), while Cu and Zn values were similar in both biological media (toenail vs hair: Cu, 7.5 vs 10.6 micrograms g-1; Zn, 129 vs 108 micrograms g-1). In toenails, all elements were positively correlated with each other. In hair, there was a close relationship only between Cd and Pb; Cd and Pb were inversely related to Zn. With the exception of Zn (no correlation), there was a minor relationship between metal levels in hair and those in toenails. Using stepwise regression analysis, seasonal variation was found to be the main factor influencing hair metal levels, while nail metal levels were mainly influenced by place of residence (with the exception of Cu concentrations, for which there were no significant predictors). Multiple correlation coefficient was higher for hair than for nails. It is concluded that, for biological monitoring, toenail clippings are less suitable than hair samples. PMID- 1882233 TI - Studies of blood lead levels in children by proton-induced X-ray emission (PIXE). AB - Blood lead levels of children admitted to Sion Hospital, Bombay (India), from the adjoining Dharavi slum areas have been determined by proton-induced X-ray emission (PIXE). Blood samples were collected from 36 children with suspected lead poisoning and from 20 control children. The analysis showed that the lead concentration of the patients varied from 0.1 to 6.0 micrograms ml-1. In addition to lead, K, Ca, Fe, Cu, Zn, Se, Br and Rb were also detected simultaneously, of which the concentrations of Fe, Cu, Zn, Se, Rb and Pb were determined. The high blood lead levels of the children from this area may be ascribed to environmental pollution due to heavy vehicular traffic and industrial sources. PMID- 1882234 TI - Comparative toxicity of organotin compounds to rainbow trout (Oncorhynchus mykiss) yolk sac fry. AB - The comparative toxicity of various organotin compounds was investigated in early life stages of the rainbow trout. Beginning with yolk sac fry, trout were continuously exposed for 110 days to tributyl- (TBTC), triphenyl- (TPhTC) or tricyclohexyltin chloride (TCHTC) at concentrations of 0.12-15 nM, to trimethyltin chloride (TMTC) at concentrations of 3-75 nM or to dibutyl- (DBTC) or diphenyltin chloride (DPhTC) at 160-4000 nM. The diorganotin compounds DBTC and DPhTC were about three orders of magnitude less toxic than the triorganotin homologs TBTC and TPhTC. Both for DBTC and DPhTC, a no-observable-effect concentration (NOEC) of 160 nM was established, corresponding to 40 and 60 ppb, respectively. Of the triorganotin compounds, TCHTC appeared to be the most toxic, inducing 100% mortality within 1 week at a concentration of 3 nM. Only a few trout survived exposure to 0.6 nM TCHTC for 110 days. TBTC and TPhTC caused acute mortality at a concentration of 15 nM. For both TBTC and TPhTC a NOEC of 0.12 nM was established, corresponding to water concentrations of 40 and 50 ppt, respectively. Histopathological examination revealed depletion of glycogen in liver cells of both di- and triorganotin exposed fish, except in the case of TMTC. No signs of toxicity were observed in fish exposed to up to 75 nM TMTC, the highest concentration tested. Atrophy of the thymus, the most prominent sign of toxicity of di- and tributyltin compounds in mammalian species, was not observed in early life stages of rainbow trout. Tail melanization was observed in the groups exposed to 3 nM TPhTC, 3 nM TBTC, 800 nM DBTC and 800 nM DPhTC. At the end of the exposure period, resistance to infection was examined by an intraperitoneal challenge with Aeromonas hydrophila, a secondary pathogenic bacterium to fish. Resistance of bacterial challenge was found to be decreased even at the lowest-effect concentration of both di- and triorganotin compounds. PMID- 1882235 TI - Social science perspectives on HIV in the United States. Introduction. PMID- 1882236 TI - What should behavioral scientists be doing about AIDS? PMID- 1882237 TI - AIDS risk and prevention among adolescents. AB - Although relatively few teenagers have been diagnosed with AIDS and the extent of asymptomatic human immunodeficiency virus (HIV) infection among adolescents remains largely unknown, there is cause for concern about teens' risk of contracting HIV disease The incubation period (the time from initial infection to the development of full-blown AIDS) is estimated to average eight years, and therefore it is probable that most of the individuals in their twenties who have AIDS (20% of all the people with AIDS) contracted HIV during their teenage years. The sexual and drug use activities of many teenagers place them at increased risk for HIV transmission. Sexually transmitted diseases (STDs) are pervasive and a major cause of morbidity among sexually active adolescents. The rates of STDs have continued to rise even during the 'age of AIDS'. These rates are of concern since the behaviors associated with the acquisition and transmission of STDs are also the behaviors associated with HIV transmission. In addition, the presence of STDs may increase the likelihood of HIV transmission. Although condoms reduce the risk of HIV transmission, their use remains low among sexually active teenagers. Reducing or eliminating high risk behaviors is the only way to limit further spread of HIV. Effective prevention programs should be based on models and theories of risk behavior so that the programs can be designed to change those factors which lead to the undesirable risky behaviors. The AIDS Risk Reduction Model (ARRM) is presented as an example of such a social-physiological model. The ARRM model characterizes why people persist in engaging in high risk activities or make efforts to alter those activities. The three stages theorized to be necessary to reduce risky sexual activities are: (1) recognizing that one's activities make oneself vulnerable to contracting HIV; (2) making the decision to alter risky sexual behaviors and committing to that decision; (3) overcoming barriers to enacting the decision, including problems in sexual communication and seeking help when necessary to learn strategies to reduce risky behaviors. Each stage includes a number of constructs identified in prior research as important for engaging in 'healthy' or low risk behaviors. Innovative strategies must be developed and implemented to reach all adolescents, ranging from teenagers who attend school and live with their families to those teens who are runaways, live in detention facilities or are otherwise 'disenfranchised'. To be most effective, HIV prevention programs must utilize strategies which combine cognitive and behavioral skills training.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1882238 TI - Sexual risk reduction behaviors among young heterosexual adults. AB - Although young, sexually-active heterosexuals have always been at risk for contracting sexually transmitted diseases, the recent appearance of Acquired Immunodeficiency Syndrome (AIDS) has increased the possible peril of sexual experimentation. Currently, behaviors to reduce the risk of contracting AIDS are being widely advocated. The present study examines predictors of self-reported risk reduction behaviors in a sample of 188 young, sexually-active heterosexuals. Three factors (perceptions of personal vulnerability, sexual behaviour history, and homophobia) were hypothesized to predict levels of worry about contracting a sexually transmitted disease. Worry, in turn, was hypothesized to predict behavior change. Structural equation modeling provided support for these predictions, but found somewhat different patterns for women and men. For both sexes, higher levels of worry were a significant predictor of risk reduction behavior implementation. For women only, more extensive sexual behavior histories significantly predicted levels of worry. In contrast, for men only, perceptions of personal vulnerability and homophobia were significant predictors of worry. Results suggest that gender plays an important role in understanding cognitive predictors of sexual risk reduction behaviors. PMID- 1882239 TI - Examining ethnicity versus race in AIDS related sex research. AB - Disproportionate numbers of AIDS cases have been reported for Blacks and Latinos nationwide. The criteria used to identify and categorize individuals into these groups has resulted in limited information about the factors responsible for Blacks and Latinos being at greater risk for HIV transmission. This paper addresses the importance of the term ethnicity versus race for social science AIDS related research. Methodological issues and sampling strategies, and a variety of socio cultural factors that compliment AIDS related research with ethnic minority populations are also discussed. PMID- 1882240 TI - AIDS survey methodology with black Americans. AB - Unique substantive and methodological issues are involved in conducting survey research on sexual and HIV risk related behaviors among Americans of African descent. Problem conceptualization, sampling, design of instruments, mode of data collection, interviewer/respondent characteristics, community resistance, and data analysis and interpretation are discussed. The lack of survey research on sensitive health issues is noted. Possible methods for addressing these issues are drawn from the experiences of the authors in conducting national research on the general and at risk Black community populations. It is concluded that attention to these issues can substantially improve the quality of research on AIDS related behaviors on Black communities. Finally, it is suggested that behavioral theories and sophisticated methodological and analytic approaches, sensitive to the special cultural dimensions of racial/ethnic life in the United States, would contribute substantially to the scientific armamentarium needed to successfully meet the challenge of the AIDS epidemic. PMID- 1882241 TI - Sex, drugs and HIV: an ethnographic approach. AB - This is an ethnographic study of the sexual relationship that exists between a group of heroin addicted prostitutes and a Latino/Hispanic group of migrant undocumented workers from Mexico in Orange County, California. Some of the sexual practices elicited and observed by the ethnographer have implications for the transmission and prevention of the HIV. Of particular interest is a form of sexual behavior which is known to the participants as 'becoming milk brothers'. In this sexual practice several men have sexual intercourse with a single woman in rapid succession, allowing the possibility of HIV transmission to take place from male to female, from female to male, and from male to male. PMID- 1882242 TI - The Risk Approach: unassailable logic? AB - The Risk Approach (RA) is a framework for selective provision of health care services advocated by the World Health Organization (WHO). Although the potential utility of RA is stressed in the WHO literature, the framework remains largely untested as a basis for resource deployment. Despite this, advocates claim the logic of RA is 'theoretically unassailable'. The purpose of this paper is to challenge this claim by critically examining some of the assumptions and proposed methods contained in the WHO literature concerning RA. Two areas of concern are discussed, relating to (i) prediction and the nature of relations between markers and outcomes, and (ii) marker measurement and scoring. PMID- 1882243 TI - Change in knowledge in a coronary heart disease risk factor intervention study in three communities. AB - We investigated health and diet knowledge as it relates to coronary heart disease (CHD) in three rural areas which participated in a community-oriented CHD risk factor intervention study. Knowledge of risk factors (risk knowledge) was fairly satisfactory at baseline, but diet knowledge was poor. Males, the young, and individuals with a lower level of education had less knowledge. Intervention consisted of a 3-year small mass media programme in one community (low-intensity intervention, LII), additional interpersonal intervention to high-risk individuals in the second (high-intensity intervention, HII), and no intervention in the control community (C). In the cohorts, with the baseline survey and the follow-up study 4 years apart, knowledge improved by 8.1% points in males (7.5% in females) in the HII community and by 7.1% (6.5%) in the LII community, compared to 5.5% (4.8%) in the C community (P less than 0.01). Diet knowledge improved more than risk knowledge, and individuals with lower initial scores benefitted most. Female scored highest. Educational level made a modest positive contribution to knowledge gain, after adjusting for differences in baseline knowledge. High-risk individuals did not have better knowledge at baseline, nor did they gain more from the intervention. We conclude that community intervention over a 4 year period, based on community diagnosis and tailored to the community's needs, can improve health knowledge. PMID- 1882244 TI - Adolescents' attitudes to abortion in samples from Italy and Sweden. AB - Both Italy and Sweden have legislated abortion without grounds since the 1970s but background conditions in the two countries are bipolar. The overall purpose of the present study was to investigate a sample of adolescents from Italy and Sweden regarding their attitudes towards abortion and their knowledge of family planning and to compare the results from the two countries. A questionnaire was distributed among 400 adolescents, 177 from Stockholm, Sweden and 223 from Rome and Locri, Italy. Whereas Sweden is a relatively homogeneous country. Italy has large regional differences regarding social and other aspects. For this reason two regions of Italy were studied separately. The participants were all secondary school students. The results indicated that nearly all adolescents in both countries were concerned about abortion and its consequences, although their concern was expressed differently, in accordance with their religious and cultural norms and also with their background in sexual education. The present study raises questions concerning the knowledge level as an outcome of sex education programs. In fact comparing the answers between the Italian and the Swedish samples no particular difference, in favour of the Swedish adolescents was noticed. PMID- 1882245 TI - Misinformation about medications in rural Ghana. AB - Misuse of medications is a serious problem in developing countries where drug sales are not regulated. This study assessed drug knowledge and use in a rural Ghanaian town. We surveyed health care workers and a community population sample regarding knowledge and use of available drugs. Although drugs were used by a large percentage of the population, only a small percentage correctly described their recommended use. Doctors and medical assistants were knowledgeable in the correct use of drugs, while chemists were poorly informed. However, the majority of the non-health care worker (NHCW) population bought drugs from chemists without a prescription. We conclude that in this rural setting, chemists contributed to drug misuse by providing misinformation about drugs and selling drugs according to popular demand. Educational programs for chemists and the population regarding drug use and regulation of drug sales by chemists will be critical to drug reform in Ghana. PMID- 1882246 TI - What's important for quality of life to Indians--in relation to cancer. AB - Fifty subjects were interviewed to determine the items or issues which they considered as reflecting quality of life and how important these items were in the event of a serious illness. Peace of mind, spiritual satisfaction and social satisfaction were considered to be very important by nearly 2/3 of the subjects. Individual's functioning and level of physical and psychological health were given much less significance. Level of satisfaction was valued much higher than the level of functioning. PMID- 1882247 TI - The role of physical attractiveness in the assessment of elderly patients. AB - The degree to which patient physical attractiveness affects judgements of professionals and relatives of patients as well as the psychosocial adjustment of elderly was investigated within the context of a longitudinal quasi-experimental design. In contrast to previous analogue and cross-sectional research, no evidence was found to support the contention that physical attractiveness has a potent impact on any of the variables under study. PMID- 1882248 TI - 'Addiction' phenomenon. AB - The term "addiction" has become widespread in our society. In this article, I examine the expansion of the medical addiction metaphor to numerous types of behavior. A review of the largely self-help addiction-related literature, selling tens of millions of copies per year, reveals a common path for recovery from these addictions. Understanding the addiction self-help literature can be of help in assisting our patients. PMID- 1882249 TI - The future of CME. PMID- 1882250 TI - 'Hand in glove': a centennial observation on the surgical use of rubber gloves. PMID- 1882251 TI - Primary hyperparathyroidism and coexisting nephrogenic diabetes insipidus: rapid postoperative correction. AB - Shortly after diagnosis of primary hyperparathyroidism, a patient had serum hyperosmolality, polyuria, isosthenuria, profound potassium depletion, and elevated plasma antidiuretic hormone levels, all consistent with nephrogenic diabetes insipidus. After parathyroidectomy, serum calcium and serum osmolality levels fell concurrently. Profound potassium deficits did not recur. We propose that (1) hypercalcemia produced a concentrating defect and polyuria; (2) renal tubular acidosis and polyuria combined to produce severe potassium depletion; (3) hypokalemia potentiated the nephrogenic diabetes insipidus caused by hypercalcemia; and (4) postoperative disappearance of the diabetes insipidus confirmed its reversible, purely metabolic causes. PMID- 1882252 TI - Parathyroid adenoma manifested as pancreatitis and polyuria. AB - Although the data used to explain a relationship between hyperparathyroidism and pancreatitis remain incomplete, there does appear to be a relationship between the two. We believe our patient's clinical course strongly supports this. PMID- 1882253 TI - Magnetic resonance imaging of pulmonary artery aneurysm. AB - Pulmonary artery aneurysm is a rare condition. We have presented what we believe to be the first case in the English literature to be diagnosed by magnetic resonance imaging. PMID- 1882254 TI - Kikuchi-Fujimoto syndrome during pregnancy. AB - Necrotizing lymphadenitis of the Kikuchi-Fujimoto type developed in our patient during her first trimester of pregnancy, but she carried the infant to full term with no apparent adverse effect. Two subsequent pregnancies were not associated with reactivation of the disorder, nor with any recognizable adverse effect on the fetuses. A pregnancy should not be terminated because of Kikuchi-Fujimoto necrotizing lymphadenitis when it develops during the first trimester of pregnancy. PMID- 1882255 TI - Adult respiratory distress syndrome from sulfuric acid fume inhalation. AB - A 23-year-old man had adult respiratory distress syndrome (ARDS) caused by acute exposure to sulfuric acid fumes. The patient survived the initial hospitalization to be readmitted later with a lung abscess. After therapy, his chest roentgenogram and pulmonary function tests revealed no abnormalities except a marginally decreased DLCO, and he was without functional deficit. Noncardiogenic pulmonary edema probably resulted from direct alveolar injury caused by sulfuric acid. PMID- 1882256 TI - Fume fever and reactive airways dysfunction syndrome in a welder. AB - I have reported a case of fume fever and concurrent reactive airways dysfunction syndrome (RADS) after welding. The RADS should be added to the list of potential hazards associated with welding. PMID- 1882257 TI - Recurrent adnexal torsion and cystadenoma of aberrant ovarian tissue. AB - Torsion of the adnexa is rare, and diagnosis is difficult because of the sparse clinical findings. I describe a patient with recurrent torsion of the right adnexa, involving a cystadenoma of aberrant ovarian tissue. Her only symptom was recurrent right-sided pelvic pain. PMID- 1882258 TI - Lymphangiosarcoma associated with lymphedema in a man with Maffucci's syndrome. AB - A man with Maffucci's syndrome and lifelong lymphedema in the right lower extremity had a lymphangiosarcoma in the same extremity. Despite amputation of the limb and radiotherapy, he died several months later of pulmonary metastases. Malignancies of vascular origin rarely have been reported in this syndrome. Our patient's features suggest that lymphedema may predispose patients with Maffucci's syndrome to the development of lymphangiosarcoma. PMID- 1882259 TI - Foreign body in the gastrointestinal tract: intraluminal migration of laparotomy sponge. AB - We have reported a case of complete transluminal migration of a retained laparotomy sponge that caused repeated partial small bowel obstruction. Diagnosis was made when roentgenograms showed multiple positions of the laparotomy marker. The sponge was surgically removed. This is the 69th reported case of complete transluminal migration and distal movement of a laparotomy sponge. PMID- 1882260 TI - Amniotic fluid embolism. AB - Amniotic fluid embolism is an almost universally fatal complication of pregnancy. We have presented a case and reviewed the literature concerning this rare but catastrophic problem. PMID- 1882261 TI - Bouveret's syndrome: an unusual twist on the classic cause. AB - Bouveret's syndrome is a duodenal obstruction caused by a gallstone, manifested mostly as a gastric outlet obstruction. We have reported an instance of Bouveret's syndrome caused by two separate stones, either of which could independently have caused the obstruction. It is imperative to be sure that the obstruction is relieved before terminating the operative procedure. PMID- 1882262 TI - Candidal mediastinitis after surgical repair of esophageal perforation. AB - Candidal mediastinitis, like Boerhaave's syndrome, is uncommon, and both, if treated late or incompletely, frequently result in death. Early recognition and aggressive medical and surgical intervention are the best means to convalescence and cure in both conditions. PMID- 1882263 TI - Chylothorax complicating right upper lobectomy. AB - Chylothorax after pleuropulmonary surgery is unusual. We have described the case of a patient in whom this complication followed a right upper lobectomy. Early recognition is important to avoid potential morbidity and mortality. PMID- 1882265 TI - Streptococcus salivarius meningitis and colonic carcinoma. AB - Streptococcus salivarius caused fulminant meningitis in an elderly patient. A gastrointestinal diagnostic workup revealed an asymptomatic colonic adenocarcinoma. This first reported instance of S salivarius sepsis associated with a colonic neoplasm is not unexpected, since the organism is bacteriologically similar to S bovis, the prime bacterial indicator of occult malignancy. Exact speciation of streptococcal strains is fraught with technical difficulties, and gastrointestinal investigation may be warranted in an expanded variety of streptococcal infections. PMID- 1882264 TI - Strongyloides stercoralis hyperinfection and central nervous system involvement in a patient with relapsing polychondritis. AB - Infections caused by Strongyloides stercoralis are not uncommon in the United States. Because of the many different manifestations of hyperinfection with this nematode, a high index of suspicion is essential, especially in immunocompromised patients, for whom such infections are frequently fatal. Patients originating from endemic areas and those who have traveled to such areas, even in the distant past, should have the possibility of strongyloidiasis evaluated before initiation of immunosuppressive therapy. Once considered, the diagnosis is not difficult and can be accomplished using readily available techniques and methods. Although thiabendazole has a high incidence of side effects and may not always eradicate infection, it remains the drug of choice for disseminated strongyloidiasis. PMID- 1882266 TI - Gastrointestinal endoscopy versus radiology. PMID- 1882267 TI - Merkel's cell carcinoma. PMID- 1882268 TI - The obstetric dwindles. PMID- 1882269 TI - Obstetric practice patterns among family practice residency graduates. AB - Obstetric services are a critical health care need in the southeastern United States. Until recently, many family physicians included obstetrics as a part of their practice. In recent years there has been significant attrition from the practice of obstetrics among family physicians. This survey looks at attrition among graduates of the Tuscaloosa Family Practice Residency Program and their practice patterns, as well as the reasons family physicians give for discontinuing obstetric practice. We also discuss implications for residency curricula and remedial measures at the state and national levels. PMID- 1882270 TI - Computer-assisted comprehensive geriatric assessment in a family physician's office. AB - Family physicians and other medical care providers are beginning to realize the importance of a comprehensive assessment examination for elderly patients. The components of such an examination are well documented, and include not only the standard history and physical examination, but also evaluation of mental health, functional status, and socioeconomic status of the person. A major impediment to a family physician doing such an extensive evaluation is that most offices lack the team approach commonly used in tertiary care medical facilities. In this paper I report the implementation of a computer-assisted program that was developed for use in a private physician's office. The first 22 patients examined using this protocol are discussed. A new diagnosis was uncovered in all but three of the subjects. This finding suggests that performing comprehensive geriatric assessments in a family practice setting might create an immediate benefit in terms of patient management. PMID- 1882271 TI - Percutaneous intra-aortic balloon pump: emphasis on complications. AB - In a review of our 5-year experience with intra-aortic balloon pump (IABP) insertion I examined the complications of percutaneous IABP placement in 93 patients, and compared them with those reported in other studies in the literature. I analyzed several variables that may affect the complication rate. Of 78 patients in our series who had percutaneous IABP cardiac assist, 15 (19%) had complications, which falls into the acceptable range reported by others. Among 15 patients who had surgical placement of an IABP, the complication rate was similar at 20%. The complication rate after IABP insertions done by surgeons primarily in the operating room was compared with that from insertions done by cardiologists in the catheterization laboratory. The overall complication rate was found to be higher in the second group, 28.0% compared with 12.8%. The application of the IABP in cardiogenic shock was associated with a high complication rate (46%). On the other hand, its insertion before cardiac surgery was associated with a relatively low complication rate (9.5%). PMID- 1882272 TI - Relationship of regional fat distribution and obesity to electrocardiographic parameters in healthy premenopausal women. AB - Abdominal obesity is an independent cardiovascular risk factor. The coexistence of abdominal obesity and electrocardiographic abnormalities may facilitate the development of cardiac arrhythmias and sudden death. We determined the relationship of body fat distribution and obesity to ECG indices in 27 obese premenopausal women on an isocaloric diet. Intra-abdominal fat distribution was assessed by computerized tomography, and obesity was assessed by hydrostatic weighing. The PR, QRS, and QTc intervals, the P and QRS axes, and the P-QRS angle were determined from a resting electrocardiogram. Cardiovascular risk profile was assessed by systolic and diastolic blood pressure and plasma cholesterol and triglyceride levels. Increased deposition of intra-abdominal fat was significantly associated with prolongation of the QTc interval independent of obesity and other cardiovascular risk factors. The prolongation of the QTc interval seen with increasing intra-abdominal fat distribution may enhance susceptibility to cardiac arrhythmias. These subjects should have electrocardiographic monitoring during periods of weight loss achieved by intensive regimens. PMID- 1882273 TI - Intraoperative evaluation of intestinal ischemia: a comparison of methods. AB - Methods for evaluating intestinal ischemia include standard clinical criteria, Doppler ultrasonography, and intravenous fluorescein injection. Each has disadvantages, and a combination of methods is often used. The purpose of this study was to determine whether surface oximetry could be used to assess perfusion in an animal whose intestinal diameter approximates that of infants. Reversible arterial, venous, and arteriovenous occlusion was studied in rabbit intestines. After 6 to 8 hours of occlusion, intestinal vascularity was evaluated by the four methods listed. Doppler ultrasonography and surface oximetry were found to be unreliable tools for assessing perfusion in this animal model. We conclude that standard clinical criteria and fluorescein remain the standards for intraoperative evaluation of intestinal perfusion. PMID- 1882274 TI - The diabetic foot: consequences of delayed treatment and referral. AB - The pathophysiology of foot problems in diabetic patients is poorly understood by many physicians. Two major factors that frequently lead to a delay in appropriate treatment with subsequent limb loss are failure to appreciate the presence and severity of underlying infection and attribution of gangrene of the toe and forefoot to microvascular disease. To evaluate the consequences of delayed recognition and treatment, we reviewed the records of 55 diabetic patients with localized gangrene or infection of the forefoot in 62 limbs, treated consecutively on a single vascular surgical service over a 2-year period using a standard protocol. All appropriately treated neuropathic ulcers and forefoot infections healed in patients with palpable pedal pulses. If foot pulses were absent and arteriography confirmed large-vessel occlusive disease, foot lesions and infections likewise healed if concomitant revascularization was done. In our series, 33 bypasses were required because of severe atherosclerotic occlusive disease. Only one patient had "unreconstructable" arterial disease. Limb salvage was 86% at a mean follow-up of 12.4 months. In 16 of the patients (29%), there was a prolonged delay between initial treatment and referral for definitive care. The specific causes of delay were underestimation of the severity of foot infection in 10 patients, and lack of recognition of ischemia due to large-vessel occlusive disease in six. These delays led to more proximal levels of amputation in six patients, including three below-knee amputations in patients with limbs that were initially salvageable. PMID- 1882275 TI - Massive bone allografts for traumatic skeletal defects. AB - Large bone allograft transplants have been successfully used to reconstruct skeletal defects created by tumor resections and failed arthroplasties, but little has been reported on their use in traumatic defects. Of approximately 500 allograft procedures done at the Massachusetts General Hospital from 1979 to 1988, 11 were done for restoration of traumatic bone loss. The average age of the patients was 30 (range 11 to 71 years), and the location of the defect was the tibia or femur in 10 of the 11 patients studied. Eight osteoarticular grafts (six hemicondylar and two total condylar) and three intercalary grafts were used for six open and five closed fractures. The time from injury to reconstruction averaged 17 months (3 to 96 months). Primary reconstruction was done in three cases and a salvage procedure in eight. Patients were assessed by the operating surgeon and a physical therapist using an evaluation system that considers function, life-style, and emotional acceptance. According to the system, nine patients had excellent or good results (six hemicondylar grafts, three intercalary grafts), one patient had a fair result (total elbow graft), and one patient had failure of a total condylar graft and subsequently required an amputation. This study suggests that large bone allografts are of value in reconstructing traumatic skeletal defects, especially those involving an articular surface in a young patient. PMID- 1882276 TI - Dupuytren's contracture. AB - Dupuytren's contracture is a disease of the palmar and digital fascia that results in a flexion deformity of the fingers. Although the first case was reported more than 350 years ago, many questions remain unanswered. With our present state of knowledge, treatment remains empiric and operative intervention is the only successful mode of treatment. Controversies continue over the type of procedure used, as well as its timing. In light of the high rate of recurrence of flexion contractures after apparently successful operations, current research is being directed toward identifying a biochemical or histologic marker to indicate the probability of recurrence. PMID- 1882277 TI - Oral contraceptive drug interactions: important considerations. AB - Interactions with oral contraceptives (OCs) occur with drugs commonly used to treat epilepsy, tuberculosis, and depression. Most women are more likely to use antibiotics, analgesics, and antihistamines, which have also been shown to interact with OCs. The mechanisms behind these interactions may be hepatic microsomal enzyme induction or inhibition, interference with the enterohepatic circulation of steroid metabolites, interference with absorption, competition between two drugs for the same metabolizing enzyme, or induction of an opposite physiologic effect. Rifampin was the first drug reported to interfere with the efficacy of OCs. The anticonvulsants and certain antibiotics, namely ampicillin and tetracycline, also decrease the efficacy of OCs. Oral contraceptives also interfere with the metabolism of other drugs. Plasma concentrations of theophylline, diazepam, and certain other benzodiazepines are increased by OC steroids. Because OCs interact with a wide variety of prescription and over-the counter medications, a thorough drug history should be taken in all patients taking OCs. PMID- 1882278 TI - [Hyperpigmentation of the skin in steroid-dependent bronchial asthma]. PMID- 1882279 TI - [Criteria of selection of patients with breast cancer for organ-sparing operations]. AB - The analysis is given to a number of criteria guiding the selection of breast cancer patients for preserving surgery. The tumor size is one of the most essential criteria. Breast-sparing surgical treatment within radical resection of the breast according to the above selection proved not inferior by survival characteristics to radical mastectomy surpassing it by social and occupational results. PMID- 1882281 TI - [Surgical treatment of hematogenic spinal osteomyelitis using extra-focal instrumental fixation]. AB - A total of 78 cases with acute hematogenic vertebral osteomyelitis are analyzed. Diagnostic errors at the prehospital and hospital stages are specified in 42 cases (53.8 percent), that resulted in late start of adequate treatment. Preoperative antibacterial therapy was carried out 1 to 1.5 months before surgery consisting in radical resection of the focus with replacement of the defect with autotransplant and extra-focal++ fixation with Byzov's apparatus. After surgery the patients started exercises on days 5-10. This treatment resulted in formation of osseous block at the site of vertebral body resection in 3-4 months in 30.8 percent of cases, in 5-6 months in 57.7 percent, and in 10-12 months in 11.5 percent of patients. PMID- 1882280 TI - [Comparative evaluation of 2 schedules of administration of anti- neoplastic drugs by the CMF protocol in disseminated breast cancer]. AB - Combined chemotherapy with cyclophosphamide, methotrexate, fluorouracil (CMF) in two regimens of administration was comparatively assessed in a randomized and prospective trial. Group I patients (n = 34) received methotrexate and fluorouracil once a week and cyclophosphamide every other day for 15 days. In group II (n = 32) all the drugs were given simultaneously once weekly for 15 days. A complete and partial response occurred significantly more frequently in patients of group I (36%) versus group II (7%). The intergroup difference in toxicity appeared insignificant. PMID- 1882283 TI - [Laser irradiation in the complex treatment of post-burn esophagitis]. AB - The paper describes a combined therapy of postburn esophagitis the main component of which is exposure of the burnt area to laser irradiation. Good or satisfactory response was achieved in all the treated patients (n-27). PMID- 1882282 TI - [Experience with using extremely high frequency radiotherapy of the millimeter wave range in cerebrovascular disorders]. AB - Vascular diseases of the brain (functional transient and ischemic apoplexy, circulatory encephalopathy) in 79 patients were treated by UHF electromagnetic field of millimetric wave range. 14 patients entered the control group. The treatment results are indicative of clear-cut trend to a decrease of arterial pressure, normalization of blood glucose level, arrest of DIC syndrome development. PMID- 1882284 TI - [Extracorporeal lithotripsy in acute obstructive cholecystitis]. AB - Available is pilot experience in the use of extracorporeal shock--wave lithotripsy for acute--stage management of calculous cholecystitis running with obturation of the cystic duct in the absence of complications. Crushing of the stones resulted in elimination of the duct obturation and compression of the gallbladder in 95% of the patients, the acute episode was arrested and 50% of those treated got free of the stones. These therapeutic results are promising and evidence extracorporeal lithotripsy efficiency in acute obstructive cholecystitis. PMID- 1882285 TI - [Results of surgical treatment of cancer of the kidney with high surgical risk under hyperbaric oxygenation]. AB - Refusal of operative intervention because of high operative risk not infrequently deprives the patients of the only chance to prolong survival. Surgical treatment under hyperbaric oxygenation (HBO) creates adequate conditions for such operations as oxygen saturation of the blood and tissues prevented hypoxia developing due to the severe operative trauma and blood loss. Intraoperative and early postoperative hemodynamic and gas exchange parameters become stable. HBO extends indications for operative treatment of renal carcinoma contributing to improvement of treatment results. PMID- 1882287 TI - [Diagnostic criteria and surgical tactics in aneurysmal cerebral hemorrhage]. PMID- 1882286 TI - [Study of the renal venous outflow using digital subtraction angiography]. AB - A venous phase of digit subtraction angiography (DSA) of the kidneys was evaluated in 87 urologic patients. The subtraction allows satisfactory visualization of the renal veins. Amplification of the image and its early emergence indirectly suggest pathological arteriovenous shunt confirmed by intraoperative rheography. Investigation of the renal veins and venous outflow from the kidneys with DSA bears sufficient information and is less traumatic versus standard retrograde venography. PMID- 1882288 TI - [Calcium and arterial hypertension]. PMID- 1882289 TI - [Acute paraproctitis and anaerobic infection]. PMID- 1882290 TI - [Chemotherapy of multiple myeloma]. PMID- 1882291 TI - [Principles of therapeutic and preventive services for young pregnant women]. PMID- 1882292 TI - [Cytochemical parameters of lymphocytes in non-coronarogenic myocardial diseases]. AB - Blood lymphocyte redox enzymes were examined in 102 patients with infectious allergic myocarditis and vegetative dyshormonal +myocardial dystrophy. Dehydrogenase activity was found shifted and cellular energy balance disordered, these factors being valuable for differential diagnosis. Estimation of the lymphocytic energy plastic coefficient permits a dynamic monitoring of patient's status and helps predict the outcome of rehabilitation process. The detected metabolic shifts prompted inclusion of ++pyridoxal phosphate, a new coenzymic drug, in complex of treatment of this patient population. PMID- 1882293 TI - [Program of primary prevention of arterial hypertension at industrial plants]. PMID- 1882294 TI - [Experience with the study of the population's satisfaction with medical services]. PMID- 1882296 TI - [Control of atrial fibrillation by transesophageal electric stimulation]. PMID- 1882295 TI - [Diagnostic possibilities of Valsalva's test for detection of left-ventricular dysfunction in ischemic heart disease]. PMID- 1882297 TI - [Rheocardiographic diagnosis of an early stage of cardiac insufficiency in patients with stenocardia]. PMID- 1882298 TI - [Heart injuries]. PMID- 1882299 TI - [Diagnosis of contact mediastinitis in necrotic phlegmons of the neck]. PMID- 1882301 TI - [Sucralfate and alsucral in the treatment of uncomplicated duodenal ulcer]. PMID- 1882300 TI - [Prospects of development of radiotherapy in an oncological clinic]. AB - It is believed that new anticancer potential of radiotherapy lies in further research efforts in the fields of: clinical radiobiology, utilization of the last developments in radiological equipment, overall high quality of radiological service. Research in radiobiology should be aimed at the design of nonstandard dose fractionation, introduction of various modifiers and their combinations, prediction of individual responses of the tumor to ionizing radiation. First-hand clinical data on 3000 cases support the promise of such approach. The advantages of modern equipment could be successfully realized at the stage of confirming the diagnosis and topography++, design of the treatment schedule and in the process of radiotherapy. To warrant the same quality of radiological service rendered in large cancer research centers and provincial hospitals, the latter should be provided with relevant equipment, methodological instructions, participate in current cooperative programs. PMID- 1882302 TI - [Use of thymus gland peptides in chronic cholecystitis]. PMID- 1882303 TI - [Closed intramedullary and trans-osseous osteosynthesis in diaphyseal crural bone fractures]. PMID- 1882304 TI - [Immunologic reactions in patients with hypothyroidism after the treatment with thyroidin]. PMID- 1882306 TI - [Surgical treatment of Meckel's diverticulum]. PMID- 1882307 TI - [Cervical endoscopy in the diagnosis of the initial stages of cancer of the cervix uteri]. PMID- 1882308 TI - [Phasic activity of the heart in diabetes mellitus]. PMID- 1882305 TI - [Changes in internal organs in narcotic and drug dependence]. PMID- 1882309 TI - Pancreatic necrosis and infection--an update on management. AB - The mortality rate for acute pancreatitis complicated by necrosis and infection has remained high in spite of progress made in supportive care. This is mostly related to development of multi-organ failure and overwhelming sepsis. Early diagnosis of necrosis and infection followed by correct management are essential for improving survival. Contrast-enhanced computed tomography with the adjunct of fine-needle aspiration is reliable in detecting necrosis and infection. Several surgical treatment modalities are discussed in the literature; however, the cornerstone for improved survival in patients with infected necrosis is adequate debridement and wide drainage. This can be achieved with any modality, provided that the patients are re-explored promptly if the septic status persists. PMID- 1882310 TI - Pancreatic injuries in children. AB - Pancreatic injuries over an 11-year period were reviewed. Pedestrian motor vehicle accidents accounted for 45% of the injuries. Diagnosis was made clinically and on raised serial serum amylase levels. Eighty per cent of the patients were managed conservatively. Two patients required emergency surgery for pancreatic trauma. There were no deaths. It is concluded that a conservative approach is successful in most paediatric patients with pancreatic trauma. PMID- 1882311 TI - Significance of gastric surface epithelial metaplasia in the duodenum. AB - An experimental study was undertaken to establish whether normally occurring gastric surface epithelial metaplasia was increased in chronic duodenitis caused by explanting duodenal mucosa in dogs. All the histological changes of chronic duodenitis were observed in the explants. However, as established by morphometry, the distribution and the amount of gastric surface epithelial metaplasia remained unchanged in 9 dogs following periods of explantation from 3 months to 1 year. It was concluded that under these experimental conditions, gastric surface epithelial metaplasia was not a manifestation of chronic duodenitis. PMID- 1882312 TI - Splenic regeneration and phagocytic function after partial splenectomy in baboons. AB - Total splenectomy, especially in children, results in diminished ability to combat infection by capsulated bacteria. It is, however, uncertain how much splenic tissue is needed to maintain this ability. In this experimental study on baboons, in situ remnants after partial splenectomy were examined to evaluate regeneration and phagocytic function after injection of dual-labelled liposomes into their splenic arterial supply. The results showed that resection of as much as two-thirds of the spleen in baboons allowed sufficient regeneration to support adequate macrophage phagocytic function. PMID- 1882313 TI - Volvulus of the sigmoid colon. AB - Between 1983 and 1986, 18 patients with colonic volvulus (94.4% sigmoid, 5.6% caecal) were seen at Karadeniz Medical Faculty. There were 11 male and 7 female patients, with a mean age of 68 years. In 66.6% and 22.2% of patients respectively a palliative procedure or a Hartmann operation were performed. The recurrence rate in the palliative group was 30%. The mortality rate for all patients with volvulus was 16.8%. The palliative procedures were successful in patients in good general condition and without bowel necrosis, whereas the Hartmann operation gave successful results in patients with bowel necrosis. PMID- 1882315 TI - Management of perforated duodenal ulcers. PMID- 1882314 TI - Heparin-induced thrombocytopenia. AB - A series of 114 patients was prospectively investigated to determine the prevalence of heparin-induced thrombocytopenia. Of these patients only 7 (6.1%) were found to have the condition, and no cases of heparin-induced thrombocytopenia plus thrombosis were detected. PMID- 1882316 TI - Intrapericardial herniation. A report of 2 cases. AB - Traumatic intrapericardial rupture is an infrequent occurrence and often associated with other fatal injuries. Two cases of delayed presentations of central tendon defects and intrapericardial herniation after blunt trauma to the chest and abdomen are reported. PMID- 1882317 TI - Paralytic thoracic lordosis and lumbar kyphosis. A case report. AB - A case of post-poliomyelitis thoracic lordosis and lumbar kyphosis without scoliosis is presented. A true reversal of the normal sagittal contour of the spine is demonstrated. Surgical treatment gave a gratifying result. PMID- 1882318 TI - Pancreatic leiomyosarcoma. A case report. AB - The pancreas is an unusual site for leiomyosarcoma. Only 12 such cases have previously been reported. A case of pancreatic leiomyosarcoma in a 68-year-old man is presented and the diagnostic dilemma and management of such a tumour are discussed. PMID- 1882319 TI - Actuarial status of the HI and SMI Trust Funds. AB - This article presents the "Summary of the 1991 Annual Reports of the Medicare Board of Trustees." The Board reports that the present financing schedule for the Hospital Insurance (HI) program is sufficient to ensure the payment of benefits over the next 14 years with trust fund exhaustion occurring in 2005 if the alternative II (intermediate) assumptions are realized. Although the HI Trust Fund is financially adequate based on the short-range test, the Board believes that corrective action will be needed very soon to avoid the need for potentially precipitous changes later. For the Supplementary Medical Insurance (SMI) Trust Fund, the Board concludes that funds are sufficient to cover projected benefits and administrative costs through December 1991, but notes with concern the rapid growth in the cost of the program and recommends that Congress continue to work to curtail the rapid growth in the cost of the SMI program. PMID- 1882320 TI - Actuarial status of the OASI and DI Trust Funds. AB - This article presents the "Summary of the 1991 Annual Report of the Board of Trustees of the Federal Old-Age and Survivors Insurance and Disability Insurance Trust Funds." The Board reports the Old-Age and Survivors Insurance (OASI) Trust Fund, by itself, and the combined OASI and Disability Insurance (DI) Trust Funds meet the short-range test of financial adequacy, based on intermediate assumptions. However, under conditions that are more pessimistic than the intermediate assumptions, the DI Trust Fund would be depleted during the next 10 years. Under intermediate assumptions, the long-range 75-year estimates, excluding the effects of interest income, indicate the OASDI program will experience about 26 years of positive annual balances, with annual deficits indefinitely thereafter. Including interest, the trust funds would continue to grow, in dollars, for another decade, before steadily declining to exhaustion 50 years from now. PMID- 1882321 TI - Laser trabeculoplasty. AB - Over a decade, laser trabeculoplasty has evolved from being a novel new treatment to one that is a commonly accepted intervention in the management of open-angle glaucoma. Despite its widespread use, however, there are still many unanswered questions about laser trabeculoplasty, including its mechanism of action and the ideal treatment parameters. In this review, we will discuss the history of the technique, the clinical experience, and some of the experimental studies that have been conducted to answer the questions regarding its mechanism of action. PMID- 1882322 TI - Ocular teratology. AB - The principles of teratology are described, and animal models for research in abnormal ocular development and clinical studies of human teratogens are surveyed. A review is made of presumed ocular teratogenic agents: radiation; external environmental teratogens; maternal conditions such as infections, diabetes, and epilepsy; alcohol and drugs such as thalidomide, retinoic acid, and coumarin anticoagulants; and other agents, such as cigarettes. PMID- 1882323 TI - Scleral implants: an historical perspective. AB - Scleral implants are made of absorbable or nonabsorbable materials. One category of absorbable materials consists of donor tissue, either autogenous (fascia lata, plantaris gracilis tendon) or from cadavers (dura mater, sclera, fascia lata). A second category includes gelatin, reconstituted collagen, absorbable gut, fibrin, blood plasma, air, and sodium hyaluronate; of these, specially prepared gelatin seems to be the most useful. Nonabsorbable implant materials have proven more practical than absorbable implants. Solid silicone rubber is currently the most popular scleral implant material. It is soft, easy to handle, and well tolerated. Expandable implants, either temporary or permanent, are used in the form of a silicone balloon filled with liquid. Silicone sponge, also widely used, has the advantage of great softness. However, hydrogels seem to be the ideal scleral implants. The only one commercially available is Refojo's MAI implant. It is very soft and is not damaged by sutures, has a smooth surface, is molded in several sizes and shapes, and has small pores that microorganisms cannot penetrate. When saturated with a water-soluble antibiotic before implantation, this implant releases the antibiotic postoperatively for a longer time than any other implant material. Finally, surgical adhesives are useful when the sclera is too thin or weak to tolerate sutures. The best adhesive available seems to be isobutyl cyanoacrylate. PMID- 1882324 TI - The perils of Pauline: visual loss in a tippler. AB - A 31-year-old alcoholic woman who smoked had subacute visual loss. She was treated for tobacco-alcohol amblyopia with subsequent improvement in vision. PMID- 1882325 TI - Chlorambucil dosage should never exceed 22 mg/day: correction of typographical error. PMID- 1882326 TI - Cyclocryotherapy for glaucoma associated with keratoplasty. PMID- 1882327 TI - Seizures induced by aminooxyacetic acid in mice: pharmacological characteristics. AB - Systemic (s.c.) administration of aminooxyacetic acid (AOAA) in mice triggered clonic convulsions with a CD50 (convulsive dose) of 68 mg/kg (range 54-86). AOAA also induced clonic convulsions in mice subjected to intracerebroventricular administration of the drug with a CD50 of 0.04 mumols (range 0.028-0.06). At the onset of convulsions induced by systemic AOAA (CD97;150 mg/kg), the GAD activity in the frontal cortex and hippocampus was not affected. GABA mimetic drugs, progabide and gabaculine, had no effect on convulsions induced by AOAA. Convulsions induced by systemic administration of AOAA were blocked by diazepam, phenobarbital, and valproate. Ethosuximide, trimethadione, acetazolamide, diphenylhydantoin, and carbamazepine remained ineffective. L Phenylisopropyladenosine was also found to protect mice against AOAA-induced convulsions, whereas atropine and baclofen had no effect. The seizures induced by intracerebroventricular administration of AOAA (CD97; 0.1 mumols) were blocked by coadministration of preferential N-methyl-D-aspartate antagonists, D-(-)-2 aminophosphonoheptanoic (AP7), 3-[+/-)-2-carboxypiperazine-4-yl)-propyl-1 phosphonic (CPP), and kynurenic acid (KYNA); preferential quisqualate/kainate antagonists, 6-cyano-7-nitro-quinoxaline-2,3-dione and gamma-D glutamylaminomethylsulphonic acid, remained inactive in the range of dosages sufficient to block seizures induced by quisqualic acid or kainic acid. The antagonistic action of antiepileptic drugs effective against seizures induced by excitatory amino acids (diazepam and valproate), and drugs acting on excitatory amino acid receptors (AP7, CPP, and KYNA) upon seizures induced by AOAA suggests an involvement of excitatory neurotransmission in the convulsant action of the drug. PMID- 1882328 TI - Serial reconstructions of granule cell spines in the mammalian olfactory bulb. AB - The morphology of olfactory bulb granule cell spines and their dendrodendritic synaptic relations with mitral and tufted cell dendrites were examined using serial electron micrographs and 3D computer reconstructions. Most granule cell spines were pedunculated with large elliptical heads and necks (stems) longer than those described for exclusively postsynaptic spines elsewhere in the nervous system. The spines typically contained a mitochondrion, which most likely reflects the metabolic requirements of the presynaptic functions of these spines. In several cases multiple spine heads were observed connected to the parent dendritic trunk via a common neck. In addition, dendritic varicosities making synaptic connections were noted. In the data set sampled, all of the reconstructions supported the hypothesis of divergence of granule cell connectivity: in no instance was a granule cell found to contact repeatedly the same mitral or tufted cell dendrite. Examination of the topological organization of reciprocal dendrodendritic synaptic connections with mitral/tufted cell dendrites revealed parallel rows of spine heads on mitral/tufted secondary dendrites separated by intervening zones of several microns in which no synaptic appositions were found. The results provide evidence regarding rules of connectivity underlying the function of local circuits in mediating lateral inhibition in the external plexiform layer of the olfactory bulb. PMID- 1882329 TI - Effects of protein kinase C activators and inhibitors on membrane properties, synaptic responses, and cholinergic actions in CA1 subfield of rat hippocampus in situ and in vitro. AB - Activation and inhibition of protein kinase C (PKC) has been reported to induce several effects in hippocampus in vitro. It has been also proposed that, in hippocampus, phorbol esters mimic the effects of acetylcholine. To test whether the actions produced by PKC activators and inhibitors in situ are comparable to those induced in vitro preparations, we studied, in the CA1 region of the hippocampus both in situ and in vitro, the responses produced by activation and inhibition of protein kinase C. Once the effects of various PKC activators and inhibitors were established their interaction with muscarinic agonists was studied. The main findings were as follows: I) Extracellular studies in situ: 1) Phorbol diacetate (PDAc) enhanced the population spike and dendritic field amplitudes. Unlike ACh, it never induced disfacilitation or disinhibition. 2) The effects produced by muscarinic agonists were not occluded by prolonged PDAc applications. 3) Inhibition of PKC with H-7 induced a strong excitation manifested by induction of multiple spikes and broadening of the dendritic field response. This excitation was associated with blockade of IPSPs, represented by positive waves, at a presynaptic site, which was antagonised by PDAc suggesting the involvement of PKC. 4) Sphingosine, a dual PKC/calcium-calmodulin-dependent kinase inhibitor, did not reproduce H-7-induced responses. However, it did prevent the actions of muscarinic agonists. II) Intracellular studies in vitro: 1) PDAc applications by either iontophoresis or superfusion produced a i) depolarization; ii) increase in input resistance (RN); iii) blockade of the anomalous rectification ("sag"); iv) increase in the fast--but decrease in the slow--afterhyperpolarization (AHP); and v) reduction in excitability, measured by the repetitive firing evoked by depolarizing pulses. 2) During local (iontophoretic) applications of PDAc, the reversal potential of IPSPs was not affected significantly whereas during bath applications, it shifted toward more positive values. 3) Iontophoresis of H-7 caused a decrease in RN, hyperpolarization, and blockade of IPSPs. In conclusion, in the hippocampus, PKC can modulate the IPSPs, the anomalous rectification, and the membrane potential, but PKC is unlikely to be the major intracellular mediator of the excitatory actions of acetylcholine. The possible involvement of calcium-calmodulin dependent kinase is discussed. PMID- 1882330 TI - Evidence that changes in spine neck resistance are not responsible for expression of LTP. AB - From modeling studies it is known that changes in spine neck resistance can influence the shape of the non-linear curve relating synaptic current to synaptic conductance if the resistance of the neck approaches the synaptic input resistance. Such work also indicates that the effects of resistance will be much more pronounced for fast rather than slow synaptic currents. Accordingly, a reduction in neck resistance could produce an increase in the rapid responses generated by the quisqualate/AMPA class of glutamate receptors while only minimally affecting the slower NMDA receptor-mediated responses and thus account for the pattern of changes known to be associated with long-term potentiation (LTP). This hypothesis predicts that large reductions in synaptic conductance should have disproportionate effects on potentiated versus control responses. This was tested by using field potential recordings of synaptic currents in CA1 pyramidal cells in hippocampal slices in response to stimulation of Schaffer/commissural inputs that either received LTP-inducing stimulation or did not. Two manipulations were used to systematically reduce synaptic conductances: reductions of extracellular Ca++ and partial blockade of postsynaptic receptors. Reductions of synaptic field potentials by 40-75% by either method at control synapses were accompanied by equivalent reductions at previously potentiated synapses. These results suggest that LTP expression is not due to a change in the curves relating synaptic current to synaptic conductance as would be predicted by the spine resistance hypothesis. PMID- 1882331 TI - Regulation of spontaneous activity and oscillatory spike firing in rat midbrain dopamine neurons recorded in vitro. AB - Intracellular recordings were obtained from identified dopamine (DA) neurons in rat midbrain slices maintained in vitro. DA neuron membranes exhibited pronounced instantaneous and time-dependent anomalous rectification that showed evidence of maximal activation at average membrane potentials of -63 and -78 mV, respectively. Action potentials were followed by prominent afterhyperpolarizations (AHP) that consisted of two components. The fast component showed evidence of inactivation at -63 mV independent of the initial membrane potential, whereas the longer-duration, later component increased in amplitude at hyperpolarized potentials. Unlike DA neurons recorded in vivo, there was no evidence of spike frequency adaptation or summation of AHPs with prolonged depolarization-induced spike trains. Spontaneous spike discharge occurred via an endogenous pacemaker potential that was dependent on both TTX-sensitive and cobalt-sensitive processes. Hyperpolarizing prepulses could activate rebound pacemaker discharge, but this rebound activity was progressively blocked with larger-amplitude hyperpolarizing prepulses. DA neurons recorded in the anesthetized animal, freely moving animal, and in vitro preparations have been shown to exist in two states of activity: 1) spontaneously discharging action potentials or 2) hyperpolarized, quiescent, and nonfiring. Furthermore, although it is rare to find DA neurons in the untreated animal in transitional states of activity, quiescent neurons can be activated by stimuli that place a demand on the DA system. The evidence presented here is consistent with the hypothesis that the special combination of membrane properties of DA neurons contribute to the segregation of their activity into active or inactive states. PMID- 1882332 TI - Synaptic plasticity at crayfish neuromuscular junctions: facilitation and augmentation. AB - Simultaneous intracellular recordings from presynaptic nerve terminals and postsynaptic muscle fibers were used to investigate the extent to which changes in presynaptic voltage may contribute to short-term facilitation and augmentation of transmitter release at neuromuscular junctions of the crayfish (Procambarus simulans) opener muscle. Presynaptic nerve terminals have an average resting membrane potential of about -80 mV, single action potentials have an average foot to-peak amplitude of about 98 mV, and single action potentials are followed by a depolarizing after potential (DAP) of about 10 mV. During stimulus trains of 9-16 impulses at 100 Hz, amplitudes of excitatory postsynaptic potentials (EPSPs) continuously facilitate up to 100-fold. This dramatic facilitation is associated with only slight increases in the peak voltage and duration of APs for the first 2-4 pulses in such a stimulus train. Foot-to-peak total amplitude of APs usually decreases after the first pulse in a stimulus train. The data strongly suggest that short-term facilitation is not due to changes in the amplitude or duration of APs invading the presynaptic terminal. Upon cessation of a longer stimulus train, the presynaptic terminal exhibits a hyperpolarizing after potential (HAP) up to 16 mV in amplitude depending upon the frequency (10-100 Hz) and duration (1 10 sec) of the tetanic stimulation. This post-tetanic HAP decays with a time constant of 10-20 sec, which is approximately equal to the third time constant of decay in EPSP amplitude (augmentation) following tetanic stimulation. Hence, presynaptic voltage changes and/or processes associated with these voltage changes (e.g., accumulation of ions, changes in ionic conductances, etc.) may be partly responsible for augmentation of EPSP amplitudes. PMID- 1882333 TI - Synaptic plasticity at crayfish neuromuscular junctions: presynaptic inhibition. AB - Intracellular recordings at sites electronically near terminals of the opener excitor axon in the claw of crayfish (Procambarus simulans) show that stimulation of the inhibitor neuron produces hyperpolarizing or depolarizing presynaptic inhibitory potentials (PIPs). GABA applied anywhere along the length of the opener excitor or inhibitor axons also produces hyperpolarizing or depolarizing potentials. The amplitude of action potentials (APs) at recording sites near some excitor terminals is reduced by an average of 6 mV during presynaptic inhibition, which also reduces excitatory postsynaptic potentials (EPSPs) by 50-70%. The time course of AP reduction equals the time course of EPSP reduction and the amount of AP reduction is independent of the sign or amplitude of the PIPs. All these data are consistent with a hypothesis that a conductance increase produced by GABA in these presynaptic terminals of the excitor axon is responsible for presynaptic inhibition. However, the effect of presynaptic inhibition upon the accumulation of short-term facilitation of excitatory transmitter release is not the same in all muscle fibers. In some terminals, the accumulation of short-term facilitation during short, high-frequency trains of action potentials which are presynaptically inhibited often equals the accumulation of facilitation without inhibition. In other terminals, short-term facilitation accumulated during presynaptic inhibition often does not equal facilitation accumulated in the absence of presynaptic inhibition. These data suggest that some other factor which may contribute to presynaptic inhibition, such as a direct effect to decrease calcium currents, may also affect short-term facilitation in some terminals. PMID- 1882334 TI - Receptor selectivity of cholecystokinin effects on mesoaccumbens dopamine neurons. AB - Extracellular recording techniques were combined with antidromic stimulation to examine the effects of C-terminal cholecystokinin (CCK) fragments and CCK antagonists on the activity of identified mesoaccumbens dopamine (MADA) neurons in chloral hydrate-anesthetized rats. These experiments were designed to determine the receptor selectivity of sulfated CCK octapeptide (CCK-8S) effects on MADA cells. Neither CCK tetrapeptide (CCK-4) nor unsulfated CCK octapeptide (CCK-8U) significantly altered MADA cell basal firing rate or responsiveness to the inhibitory effects of the D2 DA agonist quinpirole. As reported previously for ventral tegmental area DA cells, CCK-8S produced increases or decreases in the firing rate of most MADA cells sampled. CCK-8S also enhanced the sensitivity of MADA neurons to quinpirole-induced inhibition. This increase in sensitivity to quinpirole was blocked by pretreatment with the nonselective CCK receptor antagonist proglumide and the preferential CCK-A receptor antagonist CR 1409 but not by the preferential CCK-B receptor antagonist L-365,260. The inactivity of CCK-4 and CCK-8U in these tests and the results with the antagonists suggest that the effects of CCK-8S on MADA neuronal activity are mediated by CCK-A receptors. PMID- 1882335 TI - Dopamine transporters in the nucleus accumbens and the striatum have different apparent molecular weights. PMID- 1882336 TI - [Allergy--hypersensitive children]. PMID- 1882337 TI - [Allergy--control mites correctly]. PMID- 1882338 TI - [We cannot learn amidst chaos]. PMID- 1882339 TI - [Oral hygiene]. PMID- 1882340 TI - [Nurses go along]. PMID- 1882341 TI - [Clinical nursing. Faith and common solutions]. PMID- 1882342 TI - Angiotensin-converting enzyme inhibitors, an embryopathic class of drugs with unique properties: information for clinical teratology counselors. PMID- 1882343 TI - Comments on "Effects of pulsed ultrasound and temperature on the development of rat embryos in culture". PMID- 1882344 TI - Comments on "Effects of pulsed ultrasound and temperature on the development of rat embryos in culture". PMID- 1882345 TI - Editorial reply to "Comments on 'Moebius syndrome: animal model--human correlations and evidence for a brainstem vascular etiology"': case observation vs. epidemiology studies. PMID- 1882346 TI - Sensorineural hearing loss as evidenced by the auditory brainstem response following prenatal cocaine exposure in the Long-Evans rat. AB - Prenatal cocaine exposure has been associated with a variety of adverse neurological effects. Three recent studies found evidence that prenatal cocaine exposure is associated with abnormal auditory electrophysiology, suggesting abnormal processing of auditory information. The present study used the auditory brainstem response to evaluate the effects of prenatal cocaine exposure on hearing in an animal model (Long-Evans rat). We report that prenatal cocaine exposure can cause elevated ABR thresholds and latency-intensity curves consistent with a recruitment-type sensorineural hearing loss. PMID- 1882347 TI - Glucocorticoid teratogenesis in the developing nephron. AB - Although the induction of polycystic kidney disease by neonatal glucocorticoid treatment has been extensively documented, there are no data on induction of polycystic kidney disease with fetal exposure to glucocorticoids. We injected groups of pregnant Swiss Webster albino mice subcutaneously with 250 mg/kg of hydrocortisone acetate on individual days from days 1 to 19 of gestation. A control group received an equal volume of saline. Histologic analysis of 1,522 kidneys from the offspring of these animals revealed no evidence of polycystic kidneys in the control group or in offspring of animals injected before day 11 of pregnancy. A bimodal distribution of cystic kidney disease was noted in the remaining animals, with highest prevalence after injection on day 12 (50.8%) and day 17 (34.3%). We conclude that 250 mg/kg of glucocorticoids may induce polycystic kidney disease in utero, but possibly only during critical periods of metanephric development. PMID- 1882348 TI - Lack of attenuation of valproic acid-induced effects by folinic acid in rat embryos in vitro. AB - The anticonvulsant drug valproic acid (VPA) is suspected to be a developmental toxicant in humans, inducing primarily neural tube defects. The mechanism for this effect is unknown, but it has been suggested that the drug may act via a deficiency of the vitamin folic acid. We examined this possibility by concurrent treatment of rat embryos in a whole embryo culture system with VPA and folinic acid (FA), a folic acid derivative. Groups of CD rat embryos were treated with various concentrations of VPA, various concentrations of FA, or a combination of a teratogenic dose of VPA plus various levels of FA. At the end of the 44 hour culture period, each embryo was evaluated for viability (presence of a heartbeat), yolk sac circulation, presence of any malformations, morphological score, crown-rump and head lengths, as well as DNA and protein contents. The anticonvulsant did not decrease viability but did decrease yolk sac circulation and all growth and developmental endpoints in a dose-responsive manner. There was also a dose-related increase in the incidence of open neural tubes. The addition of FA alone had no significant effect on growth and development. When various concentrations of FA were added simultaneously with a teratogenic dose of VPA, there was no decrease in the incidence of open neural tubes. Growth and developmental endpoints were altered in a somewhat random fashion but were never increased to the control level. The lack of attenuation by FA was not due to instability of the compound in the culture system, nor was there a difference in the amount of FA present in the exocoelomic fluid of VPA-treated and control embryos.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882350 TI - Maternal exposure to chemical and physical factors during pregnancy and cardiovascular malformations in the offspring. AB - The possible effect of chemical and physical factors during pregnancy on the occurrence of cardiovascular malformations in the offspring was studied in 573 cases and 1,055 controls. The cases represented all verified cardiovascular malformations in Finland during 1982-1984. The controls were randomly selected from all babies born during the same period. Case and control mothers were interviewed by midwives approximately 3 months after delivery using a structured questionnaire. Maternal alcohol consumption during the first trimester of pregnancy was more common among the mothers of case infants (45.9%) than those of controls (39.6%). Exposure to organic solvents at work was slightly more prevalent among the ventricular septal defect group (12.1%) than the control mothers (7.8%). However, neither association was significant when adjusted for maternal age in logistic regression analysis. Moreover, one or both of these associations may be chance effects resulting from multiple comparisons. The risk of cardiovascular malformations was not associated with maternal smoking, or coffee, tea, or cola consumption, and was equal in urban and rural areas. Maternal exposures to anesthetic gases, pesticides, wood preservatives, microwave ovens, and video display terminals at work or home were not associated with the risk of cardiovascular malformations. It is concluded that some common environmental exposures during early pregnancy to physical and chemical factors should not necessarily be considered hazardous for the developing fetal heart. The causes of the majority of cardiovascular malformations remain unknown. PMID- 1882349 TI - Lack of teratogenicity of trans-2-ene-valproic acid compared to valproic acid in rats. AB - The teratogenicity of trans-2-ene-valproic acid (300 and 400 mg/kg) was compared with that of valproic acid (VPA; 300 mg/kg) and controls (corn oil) administered by gavage to Sprague-Dawley CD rats on embryonic (E) days 7-18. At the 300 mg/kg dose, trans-2-ene-VPA produced no change in maternal weight, number of implantations, proportion of resorptions, proportion of malformations, or fetal weight. By contrast, the same dose of VPA (300 mg/kg) reduced maternal weight during gestation, increased malformations (12.0% vs. 0.7% in controls), and reduced fetal body weight by 25.1%. An even higher dose of trans-2-ene-VPA (400 mg/kg) produced a reduction in maternal body weight during treatment and reduced fetal body weight (by 7.9%), but did not increase resorptions or malformations in the fetuses. On day E18, maternal serum drug concentrations of VPA were higher in the VPA-treated group compared with those of trans-2-ene-VPA in the trans-2-ene VPA-treated groups at 1 hr posttreatment. At 6 hr posttreatment the reverse was seen. trans-2-ene-VPA may be absorbed more rapidly and distributed differently than VPA. Overall, the data support the view that trans-2-ene-VPA at equal or higher doses than VPA is not teratogenic in rats. PMID- 1882351 TI - Multiple antigens in the rat visceral yolk sac induce teratogenic antisera. AB - Preparative isoelectric focusing was used to fractionate the supernatant from a homogenate of day 19 rat visceral yolk sac. Three fractions, of pI ranges 3.5 5.0, 5.0-7.0, and 7.0-9.0, were isolated and used to immunize rabbits, by four or six weekly injections, each containing 5 mg protein. The resulting antisera were all teratogenic when injected into rats on day 9 of gestation, but widely differing potencies were observed. The most potent antiserum was that against yolk sac components focusing in the pI 7.0-9.0 range: An optimum teratogenic dose of 50 mg protein per kg body weight was observed, and a dose of 100 mg/kg was shown to cause 100% embryonic resorption. Antiserum against the fraction focusing in the pI 3.5-5.0 range was the least teratogenic: A significant incidence of embryonic malformation and death was seen only at doses of 600 mg/kg and above. The two fractions that yielded the more teratogenic antisera were refocused over narrower pH ranges, yielding four subfractions in the pI 5.0-7.0 range and eight subfractions in the pI 7.0-9.0 range. Antisera against each of these 12 fractions were raised in rabbits; most of these antisera were shown to be teratogenic, although of differing potencies. It is concluded that the yolk sac contains many antigens that can elicit antibodies with teratogenic and yolk sac-localizing properties. PMID- 1882352 TI - Lethal and teratogenic effects of long-term low-intensity radio frequency radiation at 428 MHz on developing chick embryo. AB - Exposure of developing chick embryos to 428 MHz radio frequency (RF) radiation at a power density of 5.5 mW/cm2 for more than 20 days resulted in embryolethal and/or teratogenic effects and delayed hatching. These adverse biological effects were not due to any thermal effect of the RF radiation. We have demonstrated teratogenicity in the chick embryo as a result of protracted low-dose RF irradiation. PMID- 1882353 TI - Marked increase in the teratogenicity of the combined administration of the industrial solvent 2-methoxyethanol and radiofrequency radiation in rats. AB - Limited published animal research reports synergistic teratogenic effects following combined hyperthermia (induced by elevated ambient temperature) and administration of chemical teratogens. Radiofrequency (RF) radiation is widely used in occupational environments. Since RF radiation also elevates the body temperature of, and is teratogenic to, exposed animals, concurrent RF radiation and chemical agent administration may enhance teratogenicity. The present exploratory study, consisting of preliminary dose-finding studies and the primary study, was designed to investigate whether concurrent exposure of rats to RF radiation and the industrial solvent 2-methoxyethanol (2ME) can enhance the developmental toxicity of either agent acting alone. Preliminary dose-finding studies using small numbers of rats investigated the ability of various RF radiation conditions and doses of 2ME to produce external malformations (primarily of the paws) when administered on gestation day 13. Based on these preliminary studies, RF radiation exposure [sufficient to elevate rectal temperature to 42.0 degrees C (4 degrees C above normal for rats) for 30 min] and 2ME administration (150 mg/kg) were selected for the primary study. In the primary study, groups of 18 to 27 pregnant rats were administered RF radiation exposure and distilled water gavage, 2ME gavage and sham RF exposure, RF radiation exposure and 2ME gavage concurrently, or sham RF exposure and distilled water gavage. Pregnant rats were sacrificed on gestation day 20, and the offspring were examined for external malformations. Combined exposures enhanced the adverse effects produced by either experimental agent alone (no malformations were detected in the double sham group). Mean fetal malformations/litter increased from 14% after 2ME and sham RF (15/26 litters affected, with an average of 2 fetuses/litter malformed) and 30% after RF radiation and water gavage (10/18 litters affected, with an average of 4 fetuses/litter malformed), to 76% after the combined treatment (18/18 litters affected, with an average of 12 fetuses/litter malformed). In addition to a significant increase in the frequency of malformations, the severity of malformations also was enhanced by the combination treatment (on a relative severity ranking scale, the 2ME severity score was less than 1, the RF score was 3, and the combination score was 6). This study provided evidence of synergism between RF radiation and 2ME administration, but additional research will be required to characterize the extent of synergism between these two agents. Potential interactive effects between chemical and physical agents need to be investigated to determine the extent to which such interactions should impact occupational exposure standards. PMID- 1882354 TI - Hypothermia: teratogenic and protective effects on the development of mouse embryos in vitro. AB - Hypothermia often occurs in association with clinical conditions involving severe hypoglycemia, but its effect on embryonic development has not been well evaluated. Thus, the whole embryo culture method was used to expose day 9 (neurulating) and day 10 (early limb bud stage) mouse embryos to physiologic levels of hypothermia (35 degrees C and 32 degrees C) for 4 and 24 hr. Embryos were evaluated after 24 hours for growth and malformations and compared with controls grown at 37 degrees C. Lactate production was measured in embryos cultured for 4 hr at 32 degrees C and compared with those cultured at 37 degrees C. A 4-hr exposure to hypothermia produced little effect morphologically but reduced the rate of lactate production at both embryonic stages. A 24-hr exposure to hypothermia at 35 degrees C or 32 degrees C produced growth retardation and dysmorphogenesis in embryos undergoing neurulation. Early limb bud stage embryos were less sensitive to this treatment, with growth retardation produced only at the lower temperature. Since hypothermia is commonly associated with severe hypoglycemia in cases of diabetic insulin overdose, day 9 (neurulating) mouse embryos were exposed concurrently to short periods of hypothermia and hypoglycemia and compared with embryos cultured in hypoglycemic medium at normal temperature. The results demonstrate that hypothermia partially protects embryos against the dysmorphogenic effects of hypoglycemia. A balance of metabolic rate and available substrate is discussed as a possible mechanism for this protective effect. PMID- 1882355 TI - Abnormalities of neural tube formation in pre-spina bifida splotch-delayed mouse embryos. AB - The splotch-delayed homozygous mutant (Spd/Spd) develops spina bifida with or without exencephaly, has spinal ganglia abnormalities, and delays in posterior neuropore closure and neural crest cell emigration. The heterozygote (Spd/+) has a pigmentation defect, and occasionally neural tube defects. To investigate the underlying mechanisms, we compared the neuroepithelium in the posterior neuropore region of cytogenetically identified 15-18 somite pair Spd/Spd, Spd/+, and +/+ mouse embryos by transmission electron and light microscopy. The notochordal area and cell number in the non-fused neuroepithelium region of Spd/Spd and Spd/+ embryos were significantly reduced compared to those of normal (+/+) embryos, which suggests an abnormality in notochord elongation. In the mesoderm, the mean cell number and mean ratio of cell number to area in the non-fused region were significantly lower in the Spd/Spd compared with +/+ embryos. The distance of exposed neuroepithelium above the mesoderm in the just-fused region was significantly lower in the Spd/Spd versus +/+ embryos, which may indicate an insufficient force exerted by the mesoderm during neural tube closure. Within the neuroepithelium, significantly more intercellular space was found in Spd/Spd than in +/+ embryos indicating disorganization. The basal lamina was poorly organized and the formation delayed around the neural tube in Spd/Spd and Spd/+ embryos. All together, these results suggest an early abnormality in interactions among the neuroepithelium, mesoderm, and notochord, which may lead to the delay or inhibition of neural tube closure observed in Spd/Spd mutants. PMID- 1882356 TI - Operation Desert Storm: a Texas physician turns correspondent. PMID- 1882357 TI - TMA strategy: making sense of Medicaid. PMID- 1882358 TI - Access to care, AIDS to dominate 102nd Congress. PMID- 1882359 TI - Private enforcement of patient transfer laws. PMID- 1882360 TI - Testicular cancer: the role of the primary care physician in prevention and early detection. AB - Early detection and screening techniques along with the concept of personal responsibility for one's own health are prominent themes in medical education. Testicular cancer, its natural history, and the current approach to prevention, early detection, and diagnosis are discussed with special emphasis on the role of the primary care physician. Current community and school efforts are described along with the availability of patient education resources. Since the incidence of testicular cancer has doubled in the last 20 years, we must give more attention to educating the public by encouraging primary physicians to incorporate instruction on self-examination of the testicles into regular physical exams. PMID- 1882361 TI - Cultural differences and ethical issues in the problem of autopsy requests. AB - Cross-cultural ethical issues pervade medical care in Texas. This preliminary study concerns the particular issues that arise when an Anglo-American physician requests an autopsy from a Mexican-American family. The study quantified differences in autopsy rates between Mexican-American and Anglo-American patients at one San Antonio hospital. Mexican-Americans had higher rates for patients dying between the ages of 21 and 40, and after 80. Anglo-Americans had higher rates for all other age groups. Differences in autopsy rates between Mexican American and Anglo-Americans ranged from 5 to 18 autopsies per 100 deaths and varied by age group. The study also involved 33 interviews concerning Mexican American and Anglo-American culture. Interviewees identified four sources of relevant differences: (1) medicine's professional values, (2) beliefs about the power of medical science to control disease, (3) beliefs about keeping cadavers whole and unmutilated, and (4) beliefs about the sentence of the soul after bodily death. An appreciation of these value differences is the basis for requesting autopsies in culturally sensitive ways. PMID- 1882362 TI - Chancroid in Dallas: new lessons from an old disease. AB - In June 1986, an unusual number of cases of darkfield negative, nonvesicular, painful genital ulcers were noted in men presenting to the Sexually Transmitted Diseases Clinic of the Dallas County Health Department. Serologic findings were routinely nonreactive in these patients. This clinical presentation was consistent with a diagnosis of chancroid, and empiric therapy with erythromycin proved quite efficacious. A retrospective review of charts revealed several similar presentations in May. After 3 weeks of experimentation with culture media, positive cultures for Haemophilus ducreyi were obtained and confirmed by the Centers for Disease Control, definitively establishing the presence of chancroid in Dallas. By year's end, 383 cases of chancroid had been diagnosed. PMID- 1882363 TI - Do obstetrical charts present a liability risk? AB - The practice of obstetrics is well-known as a medicolegal, high-risk profession. Poor charting is considered an area of serious deficiency for physicians and especially for obstetricians. We reviewed the charting practices of obstetricians in a level II community hospital. The traditional 1- and 5-minute Apgar scores were employed as the screening criteria. Apgar scores of 7 or lower at 5 minutes were used to identify charts considered vulnerable to litigious activity. Of 1437 deliveries, 115 charts with 5-minute Apgar scores of 7 or lower were reviewed. Traditional requirements for charting, eg, history and physical exams, admission notes and diagnoses were recorded fairly consistently. However, elements such as statements of judgment, autopsy reports, scalp pHs, and extended Apgar scores that would render a chart defensible were sorely lacking. Charting skills, not necessarily the quality of care, may render obstetricians medicolegally vulnerable. PMID- 1882364 TI - Even the phone company adds to the burden. PMID- 1882365 TI - People in glass houses... PMID- 1882366 TI - The good guys win one. PMID- 1882367 TI - [Negative effects of anti-nutritional factors in animal feed on nitrogen burden of the environment and possibilities of its reduction. Nutritional physiology effects]. AB - Antinutritional factors (ANFs) protect the seed against attacks of moulds, bacteria, insects and birds. The defensive effect of ANFs is apparently related to disturbances in digestive processes in insects and microorganisms. When animals consume seeds containing ANFs, the digestive processes and growth may be disturbed in a similar manner. In the present paper, the fact is discussed that all proteins passing undigested through the small intestine will be fermentatively digested in the large intestine. The final products of the protein digested in the large intestine are excreted in the faeces or urine. For investigations into the digestion of protein in pigs and the amounts of N excreted into the environment, it is of importance to measure the ileal digestibility of protein. Studies showed that ANFs such as trypsin inhibitors, lectins and tannins present in legume seeds reduce the ileal digestibility of protein. In the case of Phaseolus beans it was found that more protein passed through the terminal ileum than was ingested with the feed. With peas was shown that ANFs reduce the ileal digestibility of protein. The carbohydrates of peas did not affect the ileal digestibility of protein, although the ileal chyme was more loose. In the case of faba beans, negative correlation of tannins with ileal digestibility of protein was observed. Calculations showed that, when ANFs were removed from peas and faba beans a considerable reduction in excretion of N into the environment can be achieved. These calculations also showed important possibilities of reducing the secretion of N into the environment by elimination of ANFs. PMID- 1882368 TI - [Negative effects of anti-nutritional factors in animal feed on the nitrogen burden of the environment and possibilities of its reduction. Pathological effects]. AB - Some pathological effects of lectins in legume seeds, particular by Phasoleus vulgaris (red kidney bean) agglutinins, on intestinal epithelial cell structure and function in a bio-assay and in various in vivo ('Self-emptying blind pouch model') and in vitro (cell- and organ culture) models are reported. PMID- 1882369 TI - [Negative effects of anti-nutritional factors in animal feed on the nitrogen burden of the environment and possibilities for its reduction]. AB - The role of legume and oil seeds in animal nutrition could be more important if negative effects of so-called antinutritional factors (ANFs) could be adequately eliminated. Processing standards to attain an optimum nutritional value will then have to be based on the nutritional evaluation of legume and oil seeds. Priorities in studying the effects of processing these raw materials are to attain an optimum degree of nutritional value of protein rather than the reduction of ANFs. Obviously, reduction of proteinaceous ANFs can be accomplished by thermal methods of treatment. Residual activities of the ANFs alone, however, do not predict the quality of protein in vivo, in every case. Other factors (storage protein, carbohydrates) may also be important in addition to ANFs. This means that elimination of ANFs alone however, cannot always ensure a sufficient increase in digestibility as determined in experimental studies in animals. By correlating the results of technological experiments with those of trials in animals, optimum information may be gathered in attempting to attain an optimum nutritional value by technological methods of treatment. This will contribute to a more correct and accurate understanding of the effects of animal feed technology on the performance of animals and the consequences for the excretion of undigested nutrients in the environment. PMID- 1882370 TI - [Manual embryo reduction of twin pregnancy in the mare]. PMID- 1882371 TI - [A method for the quantification of estrus symptoms in mares]. AB - As part of the veterinary surveillance of horse breeding management, the veterinarian is increasingly often requested to predict ovulation and to give a breeding or insemination advice accordingly. The result of a teasing procedure is indispensable for this advice. A suggestion is made for the quantification of oestrus signs. Oestrus symptoms are classified into four categories. In addition, various factors are mentioned, which affect the result of a teasing procedure. PMID- 1882372 TI - [A case of piglet mortality caused by the combination salinomycin and tiamulin]. PMID- 1882373 TI - [Feeding of parrots]. PMID- 1882374 TI - Aortic root replacement--20 years experience of the use of homografts. AB - The aortic root was replaced with a free root homograft 100 times in 91 patients from 1970 to January 1987. The ages of the patients were in the range 5-73 years (mean 29.7). There were 63 males and 34 females. Thirty had endocarditis with root abscesses. Forty-one had congenitally small aortic roots and 20 patients had such severe root calcification that root replacement was required. One patient had an aortic sinus aneurysm repaired using this technique. Operative mortality (overall 24%) analysed by operative indication was highest for prosthetic endocarditis (33%). 20% of those with root calcification and 15% of those operated on for hypoplastic roots died. Endocarditis was cured in 19 of 20 survivors. One patient needed repeat root replacement to achieve this. Thirteen patients out of 35 survivors in the hypoplastic group were restudied. Mean subvalvular gradient was 12 +/- 9 mmHg (range 0-27 mmHg). Late mortality was lowest in the endocarditis group (5%), and 11% in the hypoplastic group. There were 4 (24%) late deaths in the root calcification group but 2 were non cardiac. Eight homograft roots failed, two in the endocarditis group and one in the hypoplastic group due to endocarditis. The remainder failed because of 'wear and tear'. Five were replaced using homografts and one by a composite graft. Two were treated by prosthetic subcoronary aortic valve replacement with pericardial patch enlargement of the root. A further patient with Marfan's syndrome had an infected composite graft. This was replaced by a homograft root. There are 5 long term survivors of 7 repeat aortic root replacements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882375 TI - Quantitative assessment of the effects of 'inodilators' on the myocardium in patients without primary cardiac insufficiency after coronary surgery: Part I- Amrinone. AB - The positive inotropic and peripheral vasodilating effect of amrinone has been measured in 20 patients without manifest cardiac insufficiency during the early (8-18 h postoperative) and late (18-48 h postoperative) recovery phase after coronary surgery. On conclusion of the surgical intervention first the aortocoronary bypass flow was compared during dobutamine and amrinone administration. It increased by 88% with amrinone and by 19% with dobutamine. Then a needle force probe was implanted in the myocardium. Directly measured local myocardial force increased not significantly by 3.5% after the first and by 5.1% after the second bolus injection of 2 mg/kg amrinone. The rate of myocardial contraction increased by 18.7% and 12%. The rate of relaxation decreased by 5.3% after the first and increased by 15% after the second injection. Mean pulmonary arterial pressure fell from 18.5 to 15.5 mmHg and from 19.7 to 17 mmHg. Cardiac output increased by 23% after the first and by 20% after the second injection. Heart rate rose from 88 to 99 bpm and from 86 to 94 bpm. Total peripheral resistance fell from 1,035 to 706 dyn*s*cm-5 and from 1,036 to 819 dyn*s*cm-5. The systolic arterial pressure fell from 132 to 116 mmHg after the first injection and did not change after the second injection. Amrinone was found to be a powerful peripheral vasodilator with a mild positive inotropic action. The variations in the effects between the early and late recovery phases mainly reflect a progressive haemodynamic stabilization with a decreasing tendency toward hypotensive disregulation. Careful consideration has to be paid to a properly balanced filling of the vascular system before administering amrinone. PMID- 1882376 TI - Factors determining ventricular fibrillation after induced cardiac arrest. AB - Ventricular fibrillation following release of the aortic cross clamp is not uncommon. In 38 patients undergoing aortic valve replacement we investigated if this disturbance of rhythm is due to perioperative myocardial ischemia or due to deterioration of myocardial function prior to surgery. In all cases hypothermic cardioplegic arrest (Bretschneider) was used. The mean duration of ischemia was 49.39 +/- 10.46 minutes. After release of the aortic cross clamp in 17 of 38 patients ventricular fibrillation occurred. To find out which factors are responsible for the occurrence of ventricular fibrillation we performed a statistical analysis. Thereby we found out that the occurrence of ventricular fibrillation did not correlate with ischemia, the maximal level of myocardium bound creatine kinase, the NYHA stage, or the left ventricular end diastolic pressure. The left-ventricular concentration of noradrenaline determined just before release of the aortic cross clamp showed a significant negative correlation with the occurrence of ventricular fibrillation. From our results we conclude that ischemic injury was not the determining factor for the occurrence of ventricular fibrillation in our study. We suggest that the significant correlation with reduced myocardial noradrenaline content demonstrates that myocardial deterioration prior to surgery is the determining factor for the occurrence of ventricular fibrillation. PMID- 1882377 TI - Pulmonary stenosis with intact ventricular septum: assessment and indication of reconstructive surgery for residual right-ventricular outflow tract obstruction. AB - If not all of the right ventricular outflow tract obstruction (RVOTO) is removed in the operation for pulmonary stenosis, high right ventricular pressure can sometimes occur afterward. However, it is not easy to assess the amount of RVOTO that is to be removed, and there is no quantifiable method for selecting operative procedures. The aim of this report is to discuss the formulation of a numerical indicator, based on the parameters peak systolic right-ventricular pressure (RVP), systolic systemic arterial pressure (AP), pulmonary valvular orifice size (VS), and body surface area (BSA), from the results obtained in sixty-four open heart surgeries for pulmonary stenosis with intact ventricular septum. A group, in which an outflow tract patch was not used and which had a higher pre-operative RVP/AP ratio, had a tendency to have a correspondingly higher RVP/AP ratio one month after the operation. Most patients with a high RVP/AP ratio one month after the operation showed a significant decrease in this ratio a long time after the operation. But, there were exceptions to this rule where the ratio remained high. Reconstruction of the right ventricular outflow was considered for some patients whose RVP/AP ratios remained high. Reconstruction of the RVOT by using an outflow tract patch worked well for patients with an associated infundibular stenosis. A subannular patch was used for patients with infundibular stenosis, and a transannular patch was used for patients with annular stenosis. The optimal annulus size was such that VS/BSA was not less than 2 cm2/m2. A transannular monocusp patch was applied to an area which was more than 10 mm wide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882378 TI - Prosthetic bypass and flow reversal in the dissecting thoraco-abdominal aortic aneurysm. AB - In 1981 Carpentier and Co-workers introduced an alternative surgical procedure for great dissecting thoraco-abdominal aortic aneurysms, departing from the resection and the orthotopic implantation of a prosthesis (graft inclusion technique). Compression of the aneurysmatic false lumen from the inside under stepwise thrombosis of the aneurysmal sac with conservation of the main arterial origins was achieved by prosthetic bypass of the diseased vascular part and a flow reversal in the dissected aortic region by an oblique suture across the aortic lumen after the origin of the left subclavian artery. This procedure, distinguished by rather little effort and few complications (bleeding, ischaemic spinal cord damage) is described for all stages of dissecting thoracal aortic aneurysms. In the last 2 years this operation was performed in our department on 4 patients (1 m. 3 f) suffering from an acute dissecting thoraco-abdominal aortic aneurysm (Stanford type B). 2 patients died in the early postoperative period, one from a redissection close to the proximal anastomosis, the other due to the critical cardiac situation. 2 patients could be followed up postoperatively 10 and 27 months. In both cases no signs of minor perfusion of the spinal cord, the kidneys, or the mesenterial organs were observed. In both cases a partial thrombosis of the aneurysmal sac with intact blood stream to the major vessels in these regions could be demonstrated by sonography, angiography or DSA, and computer tomography. The concept of flow reversal proved to be an alternative to major resection procedures. PMID- 1882379 TI - Reduction of granulocyte-mediated lung injury in canine cardiopulmonary bypass by anisodamine infusion. AB - The effect of infusing the M-cholinergic receptor blocker anisodamine during cardiopulmonary bypass (CPB) on granulocyte-mediated lung injury was evaluated in sixteen dogs undergoing CPB for 120 min with the aorta crossclamped for 90 min. The treated dogs (n = 8) received a total dose of 15 mg/kg anisodamine hydrochloride before and during CPB whereas the controls (n = 8) received saline only. A significantly reduced sequestration of granulocytes in the lungs was found in the treated dogs as indicated by a lower right-to-left atrium granulocyte gradient 15 minutes after pulmonary recirculation during CPB (p less than 0.05) and less granulocyte accumulation in the lung capillaries after CPB, as shown by histological examination (p less than 0.01). Moreover, oxygen free radical release as indicated by plasma malondialdehyde concentrations was significantly lower (p less than 0.05) in the treated dogs than in the controls towards the end of CPB. Finally, a significantly reduced lung-water content was found 30 min after CPB in the treated dogs as compared with the controls (p less than 0.01). These results suggest that anisodamine administration in this experimental model significantly inhibits pulmonary granulocyte sequestration in CPB and the consequent lung injury induced. PMID- 1882380 TI - Computed tomography in the pre-operative assessment of mediastinal tumours--does it improve surgical management? AB - Computed tomography (CT) provides detailed imaging of the mediastinum. To assess whether this information improves subsequent surgical management 39 consecutive cases were reviewed. 21 patients had pre-operative CT of the mediastinum (CT group); 18 did not (No-CT group). The pre-operative use of CT resulted in the correct assessment of tumour consistency in 20 patients, the correct extent of invasion in 16, and the correct diagnosis in 10. In 15 of the 39 cases the surgical management was inappropriate because exploration was performed for an inoperable tumour, where no tumour was found, or when nonsurgical treatment was indicated. The number of inappropriate procedures was significantly lower in the CT group. These results suggest that the routine use of CT in the assessment of mediastinal tumours is justified by a subsequent improvement in surgical management. PMID- 1882381 TI - The importance of early detection and therapy of reexpansion pulmonary edema. AB - Three cases are reported of unilateral pulmonary edema, two following rapid reexpansion after prolonged tension pneumothorax, with total collapse of the right lung and one after reexpanded atelectasis following left intrabronchial obstruction. In all cases decrease of blood pressure and tachycardia not responding to intravenous fluid substitution were already present within the first 15 min after chest drainage or after removal of the intrabronchial obstruction. The preexistent dyspnea failed to improve. A cloudy opacity of the reexpanded lung was found immediately after drainage in 2 cases. After immediate application of a continuous positive airway pressure mask no more extensive therapy was necessary in one patient. The two others in whom treatment was begun with more than 1 hour delay required artificial ventilation and adrenergics for 2 and 4 days, respectively. PMID- 1882382 TI - Cardiac surgery in the Federal Republic of Germany during 1990. A report by the German Society for Thoracic and Cardiovascular Surgery. PMID- 1882383 TI - Pyloric narrowing with increased fibrous tissue of the mucosa in an infant. AB - An infant with pyloric narrowing following bilious vomiting is described. Barium meal studies demonstrated fixed narrowing of the pyloric canal similar to infantile hypertrophic pyloric stenosis. However, sonographic examination failed to prove significant muscular hypertrophy of the pylorus. Histology of the pre pyloric mucosal biopsy specimens showed nonspecific inflammation with increased fibrous tissue of the mucosa. Repeated histological examination revealed regression of mucosal inflammation; the patient became symptom free and normal growth was confirmed at 2 years of age. It is possible that antral/pyloric mucosal inflammation, the pathogenesis of which remains unclear, was the cause of pyloric narrowing and then led to nonbilious vomiting. PMID- 1882384 TI - Effects of d-, l- and dl-chlorpheniramine on dopamine and 3,4 dihydroxyphenylacetic acid levels in the regional parts of rat brain. AB - The purpose of this study was to further investigate the differences in the effects of optical isomers of chlorpheniramine (d-, l- and dl-forms) on the levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the regional parts of rat brain. After the intravenous administration of each form of chlorpheniramine at a dose of 20 mg/kg, the DA and DOPAC levels were measured by HPLC system. Each form of chlorpheniramine is effective in reducing DOPAC, but not DA levels in the brain of rats. The degree of reducing DOPAC levels does not correlate with the antihistaminic potency of these drugs. Thus, the present results indicate that there is a lack of stereospecificity in reducing DOPAC levels, suggesting the lack of stereospecificity in inhibiting DA reuptake. PMID- 1882385 TI - Glucocorticoid-induced central diabetes insipidus in a case of malignant lymphoma. AB - A 37-year-old man was diagnosed as malignant lymphoma infiltrating in the central nervous system with hypopituitrism and secondary glucocorticoid deficiency. In this case, plasma arginine vasopressin (AVP) increased, but glucocorticoid administration decreased plasma AVP and increased urine volume with a reduction in urinary osmolality, indicative of the presence of glucocorticoid-induced diabetes insipidus. At the terminal stage, plasma AVP did not increase in response to the withdrawal of glucocorticoid and urine volume remained decreased, suggesting the presence of masked diabetes insipidus. Autopsy showed an infiltration of lymphoid cells around the cerebral ventricles and necrosis in the hypothalamo-hypophyseal system. These findings suggested that glucocorticoid might centrally play an important role in the regulation of AVP release, and its deficiency potentiated AVP release. PMID- 1882386 TI - Chelation in metal intoxication. XXXIV. Mixed ligand chelation in lead poisoning. AB - The effectiveness of alpha-mercapto-beta-(2-furyl)acrylic acid (MFA) and N-benzyl N-dithiocarboxy-D-glucamine (NaB), used in combination, in the mobilization and excretion of lead was investigated in rats. Male Wistar rats received 10 mg Pb/kg as lead acetate intragastrically daily for 6 weeks. The lead-exposed rats were treated with either MFA or NaB or both 200 mumol/kg i.p., each, daily for 3 days. Both chelating agents provoked significant urinary and faecal excretion and lowered the soft-organ lead burden. However, combined therapy did not elicit any additive or synergistic response. PMID- 1882387 TI - Induction of metallothionein and stimulation of calcification by dexamethasone in cultured clonal osteogenic cells, MC3T3-E1. AB - To clarify the effects of dexamethasone (Dex) on metallothionein (MT) synthesis and calcification in osteoblastic cells, a clonal osteogenic cell line (MC3T3-E1) was used in the present study. Under culture conditions designed not to cause calcification, MT synthesis of cells at 3 days after inoculation increased with increasing concentration of Dex (2.5-50 nM) for a 24-h culture period. Cells at 6 or 9 days after inoculation also synthesized MT by a 24-h exposure to Dex. These show that undifferentiated osteoblasts have the ability to synthesize MT by Dex. Under culture conditions designed to cause calcification, cells at 6 days after inoculation were cultured with 50 nM Dex in the presence of 7 mM beta glycerophosphate (beta-GP) for 7 days. Ca content of Dex-treated cells was about 7.5 times as high as that of untreated cells. Dex-treated cells showed a high activity of alkaline phosphatase (ALP). The Zn content of the MT fraction in Dex treated cells was about 8 times as high as that of untreated cells. These results show that Dex has the ability to induce MT synthesis in osteoblastic cells and to cause a high calcification which is due at least partly to an enhanced activity of ALP. PMID- 1882388 TI - Nickel-induced lipid peroxidation in the liver of different strains of mice and its relation to nickel effects on antioxidant systems. AB - After a single intraperitoneal injection of 170 mumol nickel(II)acetate/kg body wt., the activity of hepatic catalase (CAT) decreased by 25-56% in a strain- and time-dependent manner, the most susceptible being C57BL/6NCr greater than C3H/HeNCr-MTV- greater than B6C3F1 greater than or equal to BALB/cAnNCr mice. The glutathione (GSH) levels in all 4 strains were inhibited by nickel with the C57BL/6NCr mice showing the biggest decrease (68%) followed by BALB/cAnNCr (46%) greater than or equal to B6C3F1 (42%) greater than C3H/HeNCr-MTV- (22%). The response of hepatic glutathione peroxidase (GSH-Px) to nickel was variable and included 30% enhancement in C3H/HeNCr-MTV- or lack of biologically significant effect (max. +/- 10% variations in time) in the remaining strains. The activity of glutathione reductase (GSSG-R) increased gradually by up to 30% (48 h post injection) in B6C3F1 and C3H/HeNCr-MTV- mice or, transiently, by 15-18% (3 h), in C57BL/6NCr and BALB/cAnNCr mice. Also, in some strains, nickel significantly affected superoxide dismutase (SOD) (14-19% loss in C57BL/6NCr and B6C3F1 mice, respectively), and GSH-S-transferase (GST) (26% loss in C3H/HeNCr-MTV- mice). Lipid peroxidation (LPO) in the liver reached its highest value 24 h after nickel treatment in C57BL/6NCr (549% over the control) greater than or equal to BALB/cAnNCr (519%) greater than B6C3F1 (426%) much greater than C3H/HeNCr-MTV- (39%). In conclusion, the magnitude of nickel-induced LPO shows a reverse correlation with the extent and direction of nickel effect on GSH, GSH-Px and GSSG-R, but not on CAT, SOD or GST. PMID- 1882389 TI - Effect of buthionine sulfoximine on N-(3,5-dichlorophenyl)-2-hydroxysuccinimide and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid nephrotoxicity. AB - N-(3,5-Dichlorophenyl)succinimide (NDPS) is an agricultural fungicide which induces acute tubular necrosis as its primary toxicity. Two NDPS metabolites, N (3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-2 hydroxysuccinamic acid (NDHSA) previously have been shown to be more potent nephrotoxicants than NDPS. In addition, buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, was found to attenuate NDPS-induced nephrotoxicity. The purpose of this study was to examine the effects of BSO pretreatment on NDHS- and NDHSA-induced nephrotoxicity. Male Fischer-344 rats (4 rats/group) were administered intraperitoneally (i.p.) BSO (890 mg/kg) 2 h before NDHS or NDHSA (0.1 or 0.2 mmol/kg, i.p.) or vehicle (sesame oil, 2.5 ml/kg), and renal function monitored at 24-h intervals for 48 h. BSO pretreatment markedly attenuated NDHSA (0.1 or 0.2 mmol/kg)-induced effects on the renal functional parameters monitored. BSO pretreatment also markedly reduced NDHS (0.1 mmol/kg) induced renal effects. However, NDHS (0.2 mmol/kg) nephrotoxicity was attenuated to a lesser extent than NDHS (0.1 mmol/kg) nephropathy. These results indicate that glutathione is an important mediator of NDPS metabolite nephrotoxicity and suggests that BSO did not attenuate NDPS nephropathy by inhibiting NDPS biotransformation to NDHS or NDHSA. PMID- 1882390 TI - Effects of zinc toxicity on thyroid function and histology in broiler chicks. AB - Mechanisms of zinc (Zn) toxicity are incompletely understood and data regarding potential endocrine alterations in Zn toxicity are scarce. To examine mechanisms of Zn toxicity, day-old chicks were pair-fed diets containing 5280 ppm (Hz) or 73 ppm (CON) Zn. Impaired postnatal growth, independent of feed consumption, and multiple endocrinopathies were observed following short-term (1-2 weeks) exposure to the high Zn diet. Reduced levels of serum cholesterol, high-density lipoprotein cholesterol, and growth hormone were associated with HZ feeding. Depressed levels of circulating thyroid hormones and histological evidence that follicle area of thyroids from HZ birds was 63% less than CON indicated that impaired growth of HZ birds may be caused, in part, by reduced thyroidal function. PMID- 1882391 TI - Trichloroaniline effects on renal function in vivo and in vitro. AB - Previous studies have demonstrated that mono- and dichloroanilines are capable of inducing acute renal failure in vivo and altering organic ion accumulation by renal cortical slices in vitro. The purpose of this study was to determine the nephrotoxic potential of 4 trichloroaniline (TCA) isomers in vivo and to examine their effects on organic ion accumulation in vitro. In the in vivo experiments, male Fischer-344 rats (4 rats/group) were administered a TCA (0.8 or 1.5 mmol/kg) intraperitoneally (i.p.) or vehicle (sesame oil, 2.5 ml/kg). Renal function was monitored at 24 and 48 h. None of the TCA isomers induced marked renal effects at either time point. In vitro, all TCA isomers were effective in decreasing tetraethylammonium and p-aminohippurate accumulation by renal cortical slices at bath concentrations of 10(-3) M with 2,3,4- and 3,4,5-TCA inducing the greatest reductions. These results indicate that TCA can have a direct effect on renal function in vitro, but that the isomers tested are less potent nephrotoxicants than the nephrotoxic mono- and dichloroanilines. PMID- 1882392 TI - Hepatic involvement of two chlorinated propenes following repeated oral exposure in the rat. AB - The comparative toxicity of two chlorinated propene isomers, 1,2,3 trichloropropene (TRCP) and 1,1,2,3-tetrachloropropene (TECP), was investigated via subchronic oral administration to rats for 4 weeks. Test groups, each consisting of 5 male and 5 female rats, were exposed to 0, 3, 10, 30, 100 or 300 mg/kg/d TRCP or TECP by gavage. A separate corn oil control group was used for each chloropropene. While all rats of both sexes given 300 mg/kg/d TRCP died, only 1 female exposed to 300 mg/kg TECP died. Mean body weights were reduced in male rats given 100 mg/kg/d TRCP. With TECP, dose-related reductions in mean body weight and food consumption were seen at 100 and 300 mg/kg/d. Moderate fatty changes in the livers of high-dose TRCP-treated rats which died during the first study week were probably related to chloropropene exposure. Treatment-related necrotic/degenerative lesions of the liver were seen in both male and female rats administered 300 mg/kg/d TECP. PMID- 1882394 TI - [The forensic medical evaluation of subcapsular splenic injuries]. AB - Data on 63 cases of subcapsular spleen lesions are analyzed. Circumstances of trauma infliction period of the 2-nd stage of spleen capsule rupture, morphological types of subcapsular spleen lesions, microscopic changes in different posttraumatic periods are presented. PMID- 1882393 TI - [The morphological equivalents of the peripheral nervous system reaction in certain types of death]. AB - The article deals with the results of analysis of morphological changes in peripheral nervous system in some types of violent and sudden death. They reflect characteristics of morpho- and pathogenesis and can be used to validate the main cause of death. PMID- 1882395 TI - [Fractography of the long tubular bones of the lower extremities in trauma by blunt objects]. AB - New data on micromorphological signs of fracture of long tubular bones in normal distribution and transformation of deforming forces are presented. Fractographic signs of bone for each destructive stage, signs of repeated trauma are singled out. Interrelationship between bone microstructure and conditions of its destruction is stated. PMID- 1882396 TI - [The forensic medical determination of the site of the external application of force by the bone microdamages]. AB - The article deals with new approach to determination of site of outer force application. Investigation of bone grind pieces from zones of supposed external action resulted in detection of microfissures whose maximal concentration corresponded to the point of force application. It was stated that these microfissures precede fracture formation and occur as a result of bone loading due to plastic deformation. That's why even in bones which experienced prethreshold loads microfissures are always detected and used as expert criteria for determination of site of outer force application. Zones of soft tissue lesions, signs of permanent (residual) bone deformity in fractures of adjacent bones serve as reference points for cutting bone fragments out and using them to prepare bone grind pieces. PMID- 1882397 TI - [The differential diagnosis and the identification importance of the track of the heel of stabbing-cutting weapons in skin wounds]. AB - Data on 123 cut-stab wounds and 52 knives were examined in the course of medicolegal expert evaluation. It was found that 30 knives possessed heels which could have two forms: symmetric and asymmetric. Heel traces were seen in 16 expert evaluations (34%) in 31 wounds (25.2%) and in some of them particular features of knife blade heel were represented. Differences between butt end and heel trace according to series of signs were noted. PMID- 1882398 TI - [The forensic medical evaluation of the results of determining diatomaceous plankton in the diagnosis of drowning]. AB - Evaluation of demonstrative value of method based on diatom plankton determination as a diagnostical sign of death due to drowning was performed. Plankton was detected in the viscera in 37% of cases (as a whole 376 bodies of people who drowned in fresh water were examined). Plankton was detected in aspiration type of drowning and its mixed variant. In spastic and reflector types of drowning plankton wasn't detected. According to author's opinion this method is an objective diagnostical test to determine the cause of death of people when their bodies are found in water. PMID- 1882399 TI - [The diagnosis of sex by qualitative traits of the pelvis]. AB - Qualitative characters of sexual dimorphism were studied visually using pelvic bones of 115 men and 99 women. The drawn-up programme on sex diagnosis according to 20 osteoscopic characters of pelvic bones makes it possible to determine individual sex in 89.87% of men and 86.87% of women (reliability level exceeds 95%). PMID- 1882401 TI - [The clinico-morphological toxicodynamics of organophosphate insecticide poisonings]. AB - The article deals with investigation of dynamics of clinical morphological pattern in acute poisoning with organophosphorous insecticides. For this purpose all specific and non-specific effects of this chemical disease are classified according to the moment of their occurrence after poison exposure. Morphological equivalent of specific clinical manifestations at different stages of thanatogenesis of this poisoning was determined. It was shown that intensity of pathological process or specific density of toxic effects per time-unit is a very important criterium for assessment of severity and prognosis of poisoning. PMID- 1882400 TI - [Expertise in acute clofelin poisonings]. PMID- 1882402 TI - [The determination of ethylene glycol in blood and urine]. AB - Method of ethylene glycol isolation from blood and urine with subsequent gas chromatographic determination was developed. The method makes it possible to extract 60-80% of ethylene glycol and to detect its toxic concentration in the cadaveric blood and urine. PMID- 1882403 TI - [The effect of separate factors on the extraction of novocaine from aqueous solutions]. PMID- 1882404 TI - [The extraction of karatan metabolites from aqueous solutions]. PMID- 1882406 TI - [The diagnosis of trauma to the human body from being run over by automobile wheels]. PMID- 1882405 TI - [The detection of ephedrine by solid-phase immunoenzyme analytical and gas chromatographic methods]. AB - Comparative analysis of ephedrine derivative content in 96 urine specimen obtained from people suspected in abuse with these drugs. Physical and chemical methods of the analysis (gas and thin-layer chromatography) as well as ELISA were used. It was stated that the latter is specific for determination of compounds related to ephedrine by structure and it allows one to detect its analogues in 87 cases. Gas chromatography made it possible to detect ephedrine derivatives in 94 specimen tested and thin-layer chromatography--in 64 specimen tested. The given ELISA may be recommended for medicolegal expert purposes and narcology practice. PMID- 1882407 TI - [Information on the forthcoming lecture series in 1991 for raising the professional qualifications of forensic medical experts in physician advanced training institutes]. PMID- 1882408 TI - [The use of a mathematical model of the process of cadaveric temperature change in diagnosing the time of death under variable environmental conditions]. PMID- 1882409 TI - [The use of chromosomal analysis in the forensic medical expertise of disputed paternity]. PMID- 1882410 TI - [A nonfatal penetrating neck wound by a pointed length of metal reinforcement fitting (bar)]. PMID- 1882411 TI - [A fatal wound by the casing of a gas grenade shot from a KS-23 carbine]. PMID- 1882412 TI - [The 80th anniversary of the Department of Forensic Medicine of the 2d Moscow Medical Institute]. PMID- 1882413 TI - [The death of S. A. Esenin--facts and conjectures]. PMID- 1882414 TI - [Apropos the article by G. V. Bobro The evaluation and quality control of the work of the structural subdivisions of the Office of Forensic Medical Expertise under the conditions of an economic experiment (Sudebno-meditsinskaia ekspertiza, No. 3, 1990)]. PMID- 1882415 TI - [The diagnosis of fatty dystrophy of the liver in fresh, formalin-treated and putrefactive cadaveric material]. AB - In the course of investigation it was stated that fat hepatic dystrophy can be diagnosed by biochemical method (lipid extraction by hexane). For al this the content of extracted lipids more than 20% of dry residue evidences about the presence of fat hepatic dystrophy which is confirmed by histological detection of lipid granules whose quantity is increasing from fat dystrophy I degree (lipid content amounts up to 30% of dry residue) to fat dystrophy III degree (lipid content is more than 40%). Formalin treatment doesn't produce significant changes in lipid content and doesn't prevent biochemical diagnosis of fat dystrophy of the liver. In case of putrefied liver lipid content is increased slightly but in all periods of putrefaction lipid content in the liver in case of fat dystrophy remains significantly higher than in controls. Biochemical method may be used in diagnosis of fat hepatic dystrophy and its degree not only on fresh and formalin treated cadaveric material but also in case of markedly pronounced putrefactive changes when other methods are useless and this fact is of great value for medicolegal practice. PMID- 1882416 TI - Metabolic channeling: scrambled evidence. PMID- 1882417 TI - Confounding routes of propionate metabolism. PMID- 1882418 TI - The TPR snap helix: a novel protein repeat motif from mitosis to transcription. AB - The recently discovered TPR gene family encodes a diverse group of proteins that function in mitosis, transcription, splicing, protein import and neurogenesis. These multi-domain proteins all contain tandemly arranged repeats of a 34-amino acid motif that are presumed to form helix-turn structures, each with a 'knob' and 'hole', acting as helix-associating domains. PMID- 1882419 TI - Chlorophyll a/b-binding proteins: an extended family. AB - A large proportion of the chlorophyll in a plant is engaged in harvesting light energy and transferring it to the photochemical reaction centres. These 'antenna' chlorophylls are non-covalently bound to specific proteins to form chlorophyll protein complexes. The chlorophyll a/b-binding (CAB) polypeptides are encoded by an extended family of nuclear genes. It has recently been discovered that other proteins not known to bind chlorophyll, the early light-inducible proteins (ELIPs), are also related and could be considered part of this family. We suggest that the latter proteins may be involved in pigment biosynthesis or in assembly of the thylakoid membrane. PMID- 1882420 TI - Who's on first? The U1 snRNP-5' splice site interaction and splicing. AB - U1 small nuclear ribonucleoprotein (snRNP) is important for pre-mRNA splicing both in yeast (Saccharomyces cerevisiae) and mammalian systems. The RNA component of U1 snRNP, U1 snRNA, interacts by base pairing with pre-mRNA 5' splice sites. This article examines recent evidence suggesting that U1 snRNP is important for an early step in spliceosome assembly rather than a late step that contributes to the specificity of 5' splice-site cleavage. PMID- 1882421 TI - FACIT collagens: diverse molecular bridges in extracellular matrices. AB - The collagens form a large family of proteins. Collagen fibrils, composed of staggered arrays of fibrillar collagen molecules (types I, II, III, V and XI), provide a supporting scaffold for extracellular matrices of connective tissues. The non-fibrillar collagens are less abundant than the fibrillar collagens, but it is becoming clear that they have important functions in the matrix. Recently, a group with unique structural characteristics has been defined and named the FACIT (Fibril-Associated Collagens with Interrupted Triple-helices) group. There is evidence that these collagens may serve as molecular bridges that are important for the organization and stability of extracellular matrices. PMID- 1882423 TI - Disasters. PMID- 1882422 TI - Disasters. PMID- 1882424 TI - Training for disaster preparedness and response. PMID- 1882425 TI - Disasters: what are the needs? How can they be assessed? PMID- 1882426 TI - Monitoring and evaluation of relief programmes. AB - Information is power. Every major relief programme of the past 15 years has shown that facts and figures are an indispensable tool for health staff. A simple graph of daily mortality rates can work miracles: mobilize human and material resources, focus the attention of decision-makers, guide and refine the assistance programme that is being put in place. If you want useful data, look at these five areas: (i) mortality; (ii) incidence of the most important diseases; (iii) nutritional status; (iv) 'activities data', such as immunizations performed; and (v) the 'vital sectors', namely food, water, sanitation, shelter, etc. The most effective way of presenting information is graphically, so that anyone can see at a glance the trend from month to month. Finally, there are two golden rules. Always give feedback to the workers out in the field who are the primary source of information. And secondly, always act upon information: if your statistics do not lead to concrete action, you are probably better off not collecting them at all. PMID- 1882427 TI - Introduction to the International Decade for Natural Disaster Reduction. PMID- 1882428 TI - Water and sanitation for disasters. PMID- 1882429 TI - Management of nutrition relief for famine affected and displaced populations. PMID- 1882430 TI - Nutritional deficiencies during famine. PMID- 1882431 TI - The new emergency health kit. PMID- 1882432 TI - Early warning systems: do they work? PMID- 1882433 TI - The role of laboratory services in disease surveillance and outbreak investigation in disasters. PMID- 1882434 TI - Surgery of war and disaster. AB - Wound excision with delayed closure after 4-5 days remains the essential principle for successful war surgery. When there are mass casualties the planning of effective triage before the event is the single most important element in achieving the best for the most. PMID- 1882435 TI - Psychological effects of disaster. PMID- 1882436 TI - Psychosocial and mental health needs of refugees--experience from SE Asia. PMID- 1882437 TI - Psychological needs of Mozambican refugees--a community-based approach. PMID- 1882438 TI - Technological disasters--towards a preventive strategy: a review. AB - Technological or man-made disasters are a growth industry. Widely publicized industrial disasters like those in Bhopal and Chernobyl are only the tip of the iceberg of human and environmental risk from technological development. Other less well publicized disasters, including the contamination of food, water and air, have affected millions of people. The 'slow' technological disasters - like air pollution, pesticides, radiation, lead, asbestos and other industrial hazards - also compromise human intellectual, behavioural and physical development. Although it can be argued that there are hazards attached to virtually every industrial activity and that it is almost impossible to remove completely the risk of technological disasters, it is possible to reduce this risk by decentralizing or deconcentrating knowledge on technological processes. Global recommendations may provide a framework for priority action, but they are obviously not applicable everywhere with the same intensity. A measurement-based approach is described that is beginning to have an effect in several developing countries. PMID- 1882439 TI - Disaster preparedness and response. PMID- 1882440 TI - The global tuberculosis situation and the new control strategy of the World Health Organization. PMID- 1882441 TI - Cytokines and the Koch phenomenon. AB - We outline the mechanisms contributing to the human form of the Koch phenomenon, which we define as necrosis occurring within 24-48 h of injection of mycobacterial antigen into the skin of past or present tuberculosis patients. It is probable that tissue damage mediated in the same way occurs in the lesions themselves. We suggest that the necrosis is mediated in part by cytokines, particularly Tumour Necrosis Factor (TNF), and that this occurs for three reasons. First, Mycobacterium tuberculosis evokes an immunoregulatory abnormality characterised by raised agalactosyl IgG. This abnormality, also found in rheumatoid arthritis, Crohn's disease, and Erythema Nodosum Leprosum, seems to be associated with dysregulation of cytokine release. Secondly, M. tuberculosis itself triggers further cytokine release. Thirdly, the normally protective role of TNF is distorted by several interacting properties of components of M. tuberculosis, which render the cytokine toxic to the host tissues. The immunoregulatory abnormality may be susceptible to correction by immunotherapy. PMID- 1882442 TI - Evaluation of a polymerase chain reaction for the diagnosis of tuberculosis. AB - A polymerase chain reaction for the specific detection of Mycobacterium tuberculosis has been developed and evaluated for clinical applicability. Primers were designed to amplify a 240 base pair region in the MPB 64 protein coding gene (nts 460-700). From among 15 different DNA templates tested (including 10 species of mycobacteria) PCR amplified the DNA from M. tuberculosis complex only, demonstrating its exquisite specificity. Sensitivity studies using serial ten fold dilutions of M. tuberculosis bacilli determined the limit of detectability to be 10 organisms. A total of 143 clinical specimens were analysed. This consisted of 26 known non-tuberculous specimens (control group) and 117 specimens received at the Tuberculosis Diagnostic Service of AIIMS (test group). None of the specimens in the control group was positive by PCR. Out of 117 specimens in the test group, 19 were culture positive for mycobacteria and 17 of these isolates were identified as M. tuberculosis. All the specimens from which M. tuberculosis was grown were also PCR positive. The remaining two isolates were identified as mycobacteria other than M. tuberculosis and these two specimens were PCR negative. An additional 14 culture negative specimens were PCR positive yielding an overall M. tuberculosis positivity rate of 26.5% (31/117) compared to 14.5% (17/117) by culture. The superior sensitivity of PCR over culture was more evident in non-pulmonary cases where PCR picked up 10 cases in addition to three culture positives out of 69 specimens. On the other hand, out of 48 pulmonary specimens only four cases in addition to 14 culture positives were picked up by PCR. PMID- 1882443 TI - Sensitivity to sensitins and tuberculin in Swedish children. I. A study of schoolchildren in an urban area. AB - Non-BCG-vaccinated schoolchildren (8 or 9 years of age) were simultaneously tested on separate arms with 2 IU PPD RT23 and 0.1 microgram Mycobacterium avium sensitin RS10 or 0.1 microgram Mycobacterium scrofulaceum sensitin RS95. None of the 2819 analysed children had any known exposure to tuberculosis. A total of 3.4% reacted with an induration greater than or equal to 6 mm to PPD RT23. Half the number of children were tested with M. avium sensitin and 25.4% reacted while the remaining were tested with M. scrofulaceum sensitin and 32.4% reacted when the cut-off was 6 mm. For about 90% of the children the sensitin reaction was larger than or equal to the tuberculin (PPD RT23) reaction. Correlation analyses showed that moderate and high PPD RT23 values were combined with still higher sensitin values, indicating that the tuberculin reactions were mainly cross reactions due to the antigenic similarity between tuberculin and sensitins. The presence of birds, dogs and cats in the homes was combined with an increased frequency of children reacting to the sensitins used. The children with reactions to PPD RT23 greater than or equal to 6 mm were examined and chest X-rays were performed. None of them showed any signs or symptoms of mycobacterial disease. In non-BCG-vaccinated Swedish schoolchildren without clinical signs of tuberculosis and without known contact with a contagious tuberculous person, indurations less than 12 to 14 mm on tuberculin testing are probably caused by atypical mycobacteria. In such cases sensitin tests should be performed to verify the suspicion. PMID- 1882444 TI - Sensitivity to sensitins and tuberculin in Swedish children. II. A study of preschool children. AB - Non-BCG-vaccinated preschool children (4 or 5 years of age) were simultaneously tested on separate arms with a 2 IU PPD RT23 and 0.1 microgram Mycobacterium avium sensitin RS10 or 0.1 microgram Mycobacterium scrofulaceum sensitin RS95. None of the 762 children had any known exposure to tuberculosis. A total of 8.8% reacted with an induration (greater than or equal to 3 mm to PPD RT23 while 2% reacted with greater than or equal to 6 mm. Half the children were tested with M. avium sensitin: 18.9 and 7.8% reacted when 3 and 6 mm cut-off points, respectively, were taken. The remaining children were tested with M. scrofulaceum sensitin: 18.4 and 6.3%, respectively, reacted. In a previous study of schoolchildren aged 8 or 9 years, reactions to sensitins were considerably more frequent. Thus, sensitisation by atypical mycobacteria seems to increase from the preschool to the early school age. This finding probably reflects a continuous exposure of the children to atypical mycobacteria from various sources. The preschool children with a reaction to PPD RT23 greater than or equal to 6 mm were examined and chest X-rays were performed. All children were healthy but one child had enlarged lymph nodes in the mediastinum and abdomen. It cannot be excluded that these pathological findings were caused by atypical mycobacteria. PMID- 1882445 TI - Tuberculosis in Saudi Arabia: epidemiology and incidence of Mycobacterium tuberculosis and other mycobacterial species. AB - The epidemiology of mycobacterial infections was studied in a wide cross-section of the Jeddah population over 2 years (1987-1989). Saudis, non-Saudis and patients from a stable population attending National Guard King Khalid Hospital (NGKKH) were compared. The ratio of Saudi to non-Saudi was 1:2 and males accounted for 65% of the total. The incidence was highest among young adults although the peak varied slightly between Saudi and non-Saudi patients. Extra pulmonary tuberculosis was also preponderant among young adults, particularly females. Variants of Mycobacterium tuberculosis were investigated for the first time in Saudi Arabia. African and Asian variants were isolated from both Saudi and non-Saudi patients, the former being more numerous. Extra-pulmonary tuberculosis, particularly lymphadenopathy, accounted for a large proportion of mycobacterial infections, 59% at NGKKH. Mycobacterial species other than M. tuberculosis were fully identified and accounted for 9% of the isolates, Mycobacterium fortuitum and Mycobacterium chelonei being the two most prevalent. PMID- 1882446 TI - Tuberculous meningiomyeloradiculitis--a report of two cases. AB - Two cases of tuberculous meningitis complicated by spread to the spinal cord and nerve roots are described. Recognition of impending paraplegia by a rising cerebrospinal fluid protein content and manometric block should prompt steroid therapy as this may prevent irreversible neurological deficit. PMID- 1882447 TI - The Koch phenomenon and delayed hypersensitivity: 1891-1991. PMID- 1882448 TI - The value of routine bronchial aspirate culture at fibreoptic bronchoscopy for the diagnosis of tuberculosis. PMID- 1882449 TI - Management of jaundice occurring during antituberculosis chemotherapy. PMID- 1882450 TI - Tuberculous pancreatitis and AIDS. PMID- 1882451 TI - Bad news from north Lebanon. PMID- 1882452 TI - [Middle molecular weight peptides from rat blood serum during acute liver injury and administration of iodinated oil]. AB - A spectrum of mean-molecular blood serum peptides in rats with experimental toxic hepatitis and parenteral injection of iodinated oil has been studied using the method of gel-filtration on a sephadex G-25. It is established that the toxic hepatitis is characterized by the expressed rearrangement of the stock of mean molecular peptides with a preferential growth in the blood serum and normalization of their concentrations 24h after the injection of iodinated oil accompanied by attenuation of the organism intoxication phenomena. An increase in the content of mean-molecular peptides was registered 48 hours after the iodinated oil injection. PMID- 1882453 TI - [The effect of thiamine and its metabolites on the activity of tissue and purified lactate dehydrogenase]. AB - It is shown that thiamine and its metabolites effect lactate dehydrogenase activity and lactate content in the tissues. Thiochrome and thiamine phosphate increase the lactate level in the liver and small intestine. The given effect correlates with the inhibition of the tissue and purified lactate dehydrogenase by thiochrome. PMID- 1882454 TI - [Activity of liver and brain arginase during hypothermia]. AB - The content of urea and activity of arginase in the brain and liver have been determined in squirrels falling into hibernation and in rats with an artificial decrease of the body temperature. It is shown that the intensity of urea synthesis under hypothermia (20, 10 degrees C) in the studied organs of animals falling into hibernation remains at high level in contrast to animals without such adaptation. PMID- 1882455 TI - [The effect of neutral polymers on glutamate dehydrogenase activity of mouse liver mitochondria upon administration of endotoxin]. AB - It is shown that neutral polymers administered intraperitoneally to intact animals considerably affect glutamate dehydrogenase activity in the liver cell mitochondria as well as in the supernatant. Of the tested polymers, only polyvinyl methylacetamide and dextran inhibit a decrease in the level of mitochondrial enzyme activity which develops with administration of endotoxin. Polyvinyl pyrrolidone with molecular weight of 100 kDa, polyvinyl methylacetamide, dextran and polyvinyl caprolactam prevent an increase of glutamate dehydrogenase activity in the supernatant in case of endotoxin administration to animals. It is possibly a result of the effect of the mitochondrial structure stabilization by the above polymers. A physiological effect of polyvinyl pyrrolidone revealed as an effect on the activity level of mitochondrial glutamate dehydrogenase and in the supernatant after endotoxin administration to animals, depends on the molecular weight of the polymer. PMID- 1882456 TI - [Distribution of ]1-14C]N-palmitoylethanolamine and its metabolites in subcellular fractions of neuroblastoma C1300 N18]. AB - Distribution in dynamics of [1-14C]N-palmitoyl ethanolamine in the subcellular fractions of neuroblastoma C1300 N18 has been studied. It is shown that distribution dynamics of the label is different depending on subcellular fractions. The level of the label in cytoplasm 15 min after incubation reaches the value which remains constant till the end of the experiment. In the microsomal fraction the label is accumulated with time and becomes maximum at the end of the experiment. The highest amount of the label in the plasma membrane has been found 15 min later and then its amount falls. Parallel with this the amount of free fatty acids grows and then begins to fall simultaneously with an increase of the amount of esterified fatty acids. A considerable amount of the label of fatty acids has been determined 15 min later in the composition of di- and triglycerides of cytosol and microsomal fraction. PMID- 1882457 TI - [The effect of epidermal growth factor on protein phosphorylation in normal and transformed hepatocytes]. AB - Qualitative differences in the content of tyrosine-phosphorylated proteins in normal and transformed hepatocytes have been found using the method of two dimensional electrophoresis. Epidermal growth factor (EGF) has induced quantitative changes in the spectra of phosphotyrosine-containing proteins in normal cells and qualitative changes in the transformed ones. Results of immunoprecipitation with antibodies against phosphotyrosine permit revealing a protein with Mm 50 kDa which is subjected to EGF-dependent tyrosine phosphorylation in normal hepatocytes. The intensity of protein phosphorylation is 10 times higher in the transformed cells but the dependence of this process on the EGF is not exhibited. The role of protein-tyrosine-kinases in the transmission of a mitogenic signal and in liver carcinogenesis is discussed. PMID- 1882458 TI - [Spectral properties of myoglobins from aquatic mammals]. AB - Spectral characteristics of ferri- and ferroderivatives of myoglobins have been studied in semiwater mammals. Extinction coefficients in the visible range of the spectrum have been determined for different derivatives of the studied heme proteins. It is established that variations in the maxima and minima of different absorption bands are inconsiderable. Close positions of isobestic points have been revealed for a system of oxyglobin and reduced myoglobin obtained from the muscles of the studied animals. Changes in spectral characteristics of methmyoglobins, induced by the effect of different pH, are identical, which evidences for similarity of the surroundings of active site of the studied heme proteins. PMID- 1882459 TI - [Fibrinolysis in vitro by acylated derivatives of a plasmin-streptokinase activator complex]. AB - Three active-site-acylated derivatives of the activator plasmin-streptokinase complex have been synthesized: n-anisoyl-, n-trans-(N,N,N-trimethylamino) cinnamoyl- and n-guanidine-benzoyl-plasmin-streptokinase. Their diacylation rate constants were 4.2 x 10(-4), 2.0 x 10(-4) and 0.6 x 10(-4) s-1, respectively. Kinetics of lysis of fibrin clots, containing plasminogen or plasminogen and alpha 2-antiplasmin, by acylplasmin, by a free activator complex and by two acylated activator complexes has been studied. It is shown that in the presence of zymogen and inhibitor the effect of acylactivator, as a fibrinolytic, is 163 times more effective than that of acylenzyme and the fibrinolytic response increases with the doze of acylactivator. The rate of fibrinolysis by a free plasmin-streptokinase complex was higher without the inhibitor than that of fibrinolysis by its acylated derivatives; fibrinolytic action of acylactivators was more effective in the presence of the inhibitor. PMID- 1882460 TI - [Isolation and identification of N-terminal fragments of the A-alpha chain of bovine fibrinogen]. AB - A method is suggested to obtain and purify N-end fragments of A alpha-chain from bovine fibrinogen. To identify the N-end chain fragments the fluorescent properties of tryptophan and tyrosine composing them as well as hydrolysis by ancistron H, a thrombin-like enzyme of the snake venom, have been used for the first time. PMID- 1882461 TI - [Effectiveness of acylated thrombolytic agents in lysis of blood plasma clots from humans and various animals]. AB - Kinetics of lysis of fibrin clots from the human, guinea pig, rat and rabbit blood plasma by two active-site-acylated derivatives of the activator plasmin streptokinase complex with different reaction rate constants has been studied in vitro. It is found that lysis of blood plasma clots in guinea pig is most similar to that of man. Acyl activator dose being increased, the lysis of a plasma clot in guinea pig is accelerated. Two acyl activators exhibit higher fibrinolytic efficiency as compared to a free activator. Experiments carried out in vivo on guinea pigs with thrombosis show that acyl activators, in contrast to nonmodified plasmin-streptokinase complex induce the less system activation of fibrinolysis and the less fibrinogenolysis. PMID- 1882462 TI - [Purification of cytochrome B-561 from chromaffin granules and its physico chemical properties]. AB - A soft method of purification of cytochrome-561 from the membranes of chromaffin granules has been developed. It permits isolating a protein in its natural microsurroundings, i.e. a complex with lipids, provided that a buffer with high ionic force is used without a detergent. This method helps obtaining an electrophoretically homogeneous preparation as a high-molecular lipoprotein hexamer whose molecular weight is about 400 kDa. Basic physicochemical parameters of this preparation (subunit composition, content and composition of lipids, heme content, spectra of optical absorption of the oxidized and reduced forms) are determined. Possible presence of two forms of cytochrome b-561 in the chromaffin granules is discussed. PMID- 1882463 TI - [Catalytic properties of cathepsin B from human kidneys]. AB - Two forms of cathepsin B isolated from human kidneys possess similar properties with hydrolysis of synthetic substrates. One of the forms is characterized by the higher specific activity with hydrolysis of synthetic substrates and proteins. Low-molecular peptides with nonpolar aminoacid residue in a site and hydrophilic C-end part inhibit reactions catalyzed by the both forms of cathepsin B. Such properties are not inherent in the apoenzymes of dehydrogenases and in albumin tested as inhibitors. It is found out that a thiol group of the active site does not interact with immobilized dithionitrobenzoic acid (DTNB) in contrast to the soluble one. A limited ability of cathepsin B to interact with native proteins is apparently, due to steric inhibitors which decreases accessibility of functional groupings of the active site. PMID- 1882464 TI - [Activity of cytoplasmic NADP-dependent dehydrogenase in rat liver during induction of cytochrome P-450 by phenobarbital]. AB - Activity of oxidation enzymes of the pentosephosphate way (glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (EC 1.1.1.44), cytoplasmic malate dehydrogenase (decarboxylating oxaloacetate) (NADP+) (EC 1.1.1.40) and isocitrate dehydrogenase (NADP+) (EC 1.1.1.42) as well as the content of microsomal cytochromes b5 and P-450 in the rat liver have been studied 24 hours after 1, 2, 3, 4 and 5 intraperitoneal administrations of phenobarbital (4 mg per 100 g of the body weight). It is shown that the cytochrome P-450 content increases after a single administration of phenobarbital and then it gradually grows reaching its maximum after 4 administrations and falls after 5 administrations (though it remains high as compared to the control animals). The content of cytochrome b5 increases only after 4 administrations of phenobarbital and after 5th one it returns to the initial level. The content of microsomal gangliosides calculated per 1 mg of microsomal protein decreases after a single administration of phenobarbital and 5 days later it returns to the initial level. Activity of glucose-6-phosphate dehydrogenase increases after a single administration of phenobarbital, that of malate dehydrogenase--after 3 administrations, 6--phosphogluconate-dehydrogenase--after 4 administrations of the preparation. The 5 administrations of phenobarbital makes activity of all the mentioned dehydrogenases return to the initial level. Activity of isocitrate dehydrogenase under given conditions of the experiment does not change. PMID- 1882465 TI - [Features of thiamine diphosphate-dependent enzyme inhibition by oxodihydrothiochrome and its phosphorylated derivatives]. AB - Anticoenzyme action of new derivatives of thiamine: oxodihydrothiochrome and its mono- and diphosphoric esters has been studied in the experiments on mice. It is shown that the given compounds exert an inhibiting action on transketolase and pyruvate dehydrogenase and do not change activity of 2-oxoglutarate dehydrogenase in the animal organism. Antivitamin effect of the studied inhibitors is observed with the lower doses and in the earlier terms as compared with the other known inhibitors of thiamine-diphosphate-dependent enzymes. The preparations inhibit activity of the yeast pyruvate-decarboxylase by the mixed (with respect to thiamine-diphosphate) type (Ki for oxodihydrothiochrome and its mono- and diphosphoric esters: 2.3 x 10(-3), 7.2 x 10(-4), 5.6 x 10(-5) M, respectively). Possible mechanisms of the action of the mentioned compounds as thiamine antimetabolites are discussed. PMID- 1882467 TI - [Interaction of [3H] corticosterone from blood serum with rat liver cells during aging]. AB - It is shown that the consumption of glucocorticoids from the complexes with serum proteins by hepatocytes decreases with ageing. Transcortin-complexed decrease adenosine monophosphate binding by the liver cells but the degree of this inhibition decreases with an increase of animals' age, which is probably connected with the change in physicochemical properties of steroid-transport blood glycoprotein. PMID- 1882466 TI - [Supermolecular organization of aminotransferases and dehydrogenases of alpha ketoacid from rat brain mitochondria]. AB - A fraction of coarse mitochondria from the rat brain was deposited after short term effect of supersound to obtain "metabolones". Activity of dehydrogenases of alpha-ketoacids, succinate dehydrogenase, aspartate-, alanine- and GABA-alpha ketoglutarate amino-transferases has been determined in the supernatant liquid and in "metabolones". It is shown that dehydrogenase activity is mainly (93-100%) localized in "metabolones", while the level of aminotransferase activity in the latter is lower (72-94%). Nonproportionally high activity of aminotransferases in the supernatant liquid is found to considerably suprpass a decrease in activity of these enzymes in "metabolones" against a background of extremely scanty losses of protein (within 5%) induced by the supersound effect. A hypothetic model of a "metabolone" containing the enzymes of the Krebbs cycle and GABA-shunt is suggested. PMID- 1882468 TI - [The effect of hypoxia on oxidative phosphorylation and lipid peroxidation in rat liver mitochondria upon lung inflammation]. AB - Hypoxic trainings of rats (maintenance in the test chamber at the "altitude" 4 km above the sea level for 7 hours a day for two weeks) prevent pneumonia-induced activation of peroxidation for lipids of the liver mitochondria. This increases the phosphorylating respiration rate when lipemic serum is used as an oxidation substrate (not succinate). In these experiments the efficiency of oxidative phosphorylation (delta ADP/delta O) when either succinate and glutamate or glutamate and malate have been oxidated corresponded to the values typical of intact animals and was higher when lipemic serum was used. It is supposed that rearrangement of energy reactions of mitochondria is connected with intensification of utilization of lipids and conjugation between their oxidation and phosphorylation. This rearrangement is apparently aimed to prevent the energy deficiency in the organism which arises in patients with pneumonia. PMID- 1882469 TI - [Violent behavior among hospitalized psychiatric patients. 1. Occurrence and psychopathology]. AB - The majority of psychiatric patients are not violent during hospitalisation. A minority behave violently during hospitalisation on repeated occasions but violent episodes are mainly concerned and these do not result in corporeal injuries. Gross violence rarely occurs. Violence involves the caring staff most frequently and, more rarely, fellow patients. The patients who are most frequently violent are the most severely ill and untreated psychotic patients. The commonest diagnosis among the violent patients is schizophrenia. Younger patients are often violent. No sex differences exist for violent behaviour. Manic patients are rarely violent and depressive illness is negatively correlated with violence. Approximately 1/5 of the demented patients show violent behaviour. The review demonstrates many methodological deficiencies in the investigations mentioned and presents recommendations concerning the design of investigations in future investigations. PMID- 1882471 TI - [Psychoanalytic therapy. An orientation on Freudian psychoanalysis]. AB - About a century after the creation of psychoanalysis and more than 35 years after the first, and only, article about psychoanalysis in this journal, the author gives a review of contemporary theory and practice. The meta-scientific position of psychoanalysis is mentioned briefly and it is emphasized that Freudian psychoanalysis is simultaneously an investigation of the mind and a treatment. It is described how contemporary members of The International Psycho-Analytical Association (i.a. The Danish Psychoanalytical Society) practise. New psychoanalytical theory and its clinical impact is reviewed. The rules for the long psychoanalytic training are stated. Finally, it is described how psychoanalytic knowledge is applied technically on a large scale particularly in the form of psychotherapy. PMID- 1882470 TI - [Violent behavior among hospitalized psychiatric patients. 2. The significance of the functioning of the department and the reactions of the staff]. AB - Violence is commonest in emergency and closed departments. Lack of structure in the department and inactivity together with an authoritarian staff attitude may increase the frequencies of violent episodes. Too much therapeutic activity may also cause violence in the department. In order to reduce the frequency of episodes of violence, the staff must be adequate in number. Good contact with the patients may have a preventative effect on violence. The experience of the care staff in the treatment of psychiatric patients is of considerable significance. Massive staff changes with appointment of less experienced care staff and many temporary staff members in the department may increase the extent of violence. Training of the staff in the technique of controlling aggression may improve their ability to cope with violent situations. The effect of staff training may depend upon the content of the training programme. Medical assistance may increase the staff capacity to manage difficult situations such as violent episodes. Leaders have considerable influence on the factors which can reduce the extent of violence. Previous investigations show many methodological defects and new investigations are necessary. PMID- 1882472 TI - [Alternative treatment of lung diseases]. AB - A total of 671 patients attending two outpatient clinics for pulmonary medicine received a questionnaire about possible alternative treatment of the pulmonary disease for which they were receiving treatment. Six hundred and five questionnaires were answered anonymously. Among the 605 patients, 75 (12%) had received alternative treatment. No differences in the frequencies were observed between men and women. Employment of alternative treatment was most frequent in the age groups 20-29 and 50-59 years. Prolonged illness without definite prospects of cure such as chronic bronchitis and asthma resulted in employment of alternative treatment more frequently than briefer illness without possibility of cure (cancer of lung) or with the possibility of cure (tuberculosis, pneumonia). The patients had practically always consulted their general practitioner before the alternative therapist (94%). Half of the patients had improved, half were unchanged and only a few per cent had deteriorated. In the majority of cases, the expenses were moderate but isolated patients had, however, paid more than 10,000 Danish crowns (approximately pounds 1,000) for the alternative treatment. PMID- 1882473 TI - [Laser treatment of sinusitis in general practice assessed by a double-blind controlled study]. AB - The effect of Low Level Laser therapy (Galium-Aluminium-Arsenide laser, 30 mW/830 nm, Unilaser 2000 3B) on sinuitis was evaluated in a double-blind randomised clinical study comprising 60 patients from general practice. All patients received three treatments (90 seconds radiation on each sinus) with one to three days interval. No statistically significant differences in pain relief, well being or duration of illness were observed between patients treated with laser and a placebo. PMID- 1882474 TI - [Ingrown nail of the great toe treated with partial resection of the nail-forming matrix]. AB - During the period 1.3.1976 to 31.5.1989, 158 patients were treated for in-growing toe-nail of the great toe by partial resection of the nail-forming matrix. The average age was 26 years and the period of observation was 83 months. A questionnaire was sent to all of the patients and 119 patients with 154 nails submitted to operation replied (75.3%). Ninety-five patients (79.8%) had no discomfort and seven (5.9%) stated that the condition had improved. Ten patients (8.4%) were submitted to reoperation. Seventy-six patients (63.9%) were completely satisfied with the cosmetic result of the treatment. Significantly better results as regards discomfort were obtained in patients who had been treated preoperatively by avulsion of the nail so that infection and inflammation had resolved (p less than 0.05). The authors conclude that partial resection of the nail-forming matrix is a certain and effective method of treating in-growing toe-nail of the great toe and they recommend that the nail is avulsed prior to operation. PMID- 1882475 TI - [Immunomodulator therapy of chronic inflammatory demyelinating polyradiculoneuropathy]. AB - A group of 6 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was treated with prednisone, azathioprine, plasma exchange and/or intravenous immunoglobulin. Three of the six patients improved during treatment with prednisone and two patients with severe CIDP both showed a remarkable therapeutic response to treatment with intravenous immunoglobulin. PMID- 1882476 TI - [Acute severe polyneuropathy in hepatic porphyria]. AB - Two cases of acute polyneuropathy in patients with latent hepatic porphyria are presented. Porphyric neuropathy is a rare, serious, life-threatening disease. Since most cases are induced by drugs, early diagnosis is essential for the treatment and prognosis. Porphyria should always be considered in acute polyneuropathy. PMID- 1882477 TI - [Antiphospholipid antibodies and ischemic heart disease]. AB - A case is presented with severe ischemic heart disease and lupus anticoagulant in a 24 year old otherwise healthy male. Anticoagulation was initiated and coronary by-pass grafting was performed. Coronary biopsy showed no signs of arteritis. PMID- 1882479 TI - [Fetal ECG analysis during labor]. PMID- 1882478 TI - [Malignant neuroleptic syndrome in a 15-year old girl after a single injection of a high-dose neuroleptic]. AB - The malignant neuroleptic syndrome is a rare and fatal iatrogenic syndrome which requires rapid and effective symptomatic treatment in a somatic hospital, possibly in an intensive care unit. Relatively little medicine (neuroleptics) is employed in child psychiatry and the syndrome is, therefore, rare in child psychiatric departments. A well-defined syndrome is concerned and it is important to be able to recognise and diagnose this. PMID- 1882480 TI - [Nurses and indwelling catheters]. PMID- 1882481 TI - [Drug poisoning vs. brain death]. PMID- 1882482 TI - [The value of alcohol test as evidence]. PMID- 1882483 TI - Historical perspective and current trends in emission microscopy, mirror electron microscopy and low-energy electron microscopy. An introduction to the proceedings of the Second International Symposium and Workshop on Emission microscopy and Related Techniques. AB - Emission microscopes and related instruments comprise a specialized class of electron microscopes that have in common an acceleration field in combination with the first stage of imaging (i.e., an immersion objective lens, also called a cathode lens or emission lens). These imaging techniques include photoelectron emission microscopy (PEEM or PEM), electron emission induced by heat, ions, or neutral particles, mirror electron microscopy (MEM), and low-energy electron microscopy (LEEM), among others. In these instruments the specimen is placed on a flat cathode or is the cathode itself. The low-energy electrons that are emitted, reflected, or backscattered from the specimen are first accelerated and then imaged by means of an electron lens system resembling that of a transmission electron microscope. The image is formed in a parallel mode in all of the above instruments, in contrast to the image in scanning electron microscopes, where the information is collected sequentially by scanning the specimen. A brief history and introduction to emission microscopy, MEM, and LEEM is presented as a background for the Proceedings of the Second International Symposium and Workshop on this subject, held in Seattle, Washington, August 16-17, 1990. Current trends in this field gleaned from the presentations at that meeting are discussed. PMID- 1882484 TI - Design and performance of a high-resolution photoelectron microscope. AB - The design of a high-resolution photoelectron microscope (photoelectron emission microscope) is described. It is an oil-free ultrahigh-vacuum instrument utilizing electrostatic electron optics. New designs are presented for a specimen translator, cathode stage, aperture stop control, electrostatic hexapole stigmator, beam shutter, and camera system. These components could also be used in a low-energy electron microscope (LEEM). The theoretical resolution of this instrument is 5 nm for UV illumination near the photoemission threshold. The photoelectron microscope is now in operation at the University of Oregon, and it is achieving results within a factor of two of this design limit. PMID- 1882485 TI - A computer-aided control, design and image-processing system for electron microscopes. AB - A computer-control system for electron microscopes is described. The aim is to reduce a complex series of vacuum-system controls to a menu-driven program that simplifies the operation of the microscope. The system also incorporates image processing, notebook, computer-aided design, and communication functions. It is designed around a commercially available computer workstation. This system has been implemented on an institute-built photoelectron microscope of ultrahigh vacuum design. PMID- 1882486 TI - Experimental study of the effects of pulsed Doppler sample volume size and position on the Doppler spectrum. AB - With a pulsed Doppler system, the recorded Doppler spectrum is expected to vary depending upon the sample volume size relative to the diameter of the vessel, the position of the sample volume in the vessel and the velocity profile. In the in vitro experiments described in this paper, the velocity profile was kept constant by using steady parabolic flow in a flow model. As the Doppler sample volume size and position were changed, the maximum variations of quantitative measurements from the Doppler spectrum were determined. The maximum, mean and mode frequencies and spectral broadening index (SBI) were affected by the position of the sample volume but to a lesser degree by its length (1.5-5.0 mm) relative to the 9.5 mm beam path length across the tube. When the centre of the Doppler sample volume was moved within the central 25% of the tube, the maximum variations were as follows: maximum frequency 3-5%, mean frequency 8-9%, mode frequency 8-9% and SBI 16-18%, where the range indicates the effect of increasing the sample volume size. Based on these results obtained under steady flow conditions in vitro, it is concluded that quantification of pulsed Doppler spectra may be feasible if the sample volume is positioned within the central 25% of the vessel. PMID- 1882487 TI - Mode propagation of ultrasound in hollow waveguides. AB - It has previously been shown that there is close agreement between theoretical and experimental behaviour of pulses of ultrasound propagating in solid cylindrical waveguides. Waveguides are used in a number of areas of medical ultrasonics and it is therefore important to be able to model sound propagation in them accurately. This paper extends the analysis of guided wave propagation to hollow waveguides. In particular, frequency spectra of modes of progagation are given and theoretical group velocity curves are compared with experimental results. Signal strengths of modes propagating in both solid and hollow stainless steel waveguides of similar cross-sectional area are also compared. PMID- 1882488 TI - Ultrasonic precision thickness gauge. PMID- 1882489 TI - Stress and the endocrine hypothalamus-pituitary-testis system: a review. AB - Stressors generally induce a depression of the hypothalamus-pituitary-testis (HPT) system, mediated by the activated hypothalamus-pituitary-adrenocortical (HPA) system, resulting in a fall in plasma luteinising hormone (LH) and testosterone levels. Hypothalamic gonadotrophin-releasing hormone (GnRH) secretion may be suppressed by endogenous opioid peptides (EOP) and/or corticosteroids. The latter dramatically enhance the negative feedback effects of testosterone on both the hypothalamus and pituitary. Pituitary gonadotrophin secretion may be reduced by adrenocorticotrophic hormone or by EOP of hypothalamic or pituitary origin. Decreases in plasma concentrations of testosterone, independent of gonadotrophins, can be induced by corticosteroids. These hormones might reduce the number of Leydig-cell LH-receptors or occupation of LH-receptors. Testicular steroidogenesis may also be inhibited by pro opiomelanocortin-derived (opioid) peptides secreted by the Leydig cells. There are some indications of increases in LH and testosterone during acute stress and, in dominant male animals, during the stress of social conflict. The latter finding indicates a difference in stress response between dominant and subordinate males. In subordinate males, decreased feedback sensitivity may allow hypersecretion throughout the HPA system. As a result, corticotrophin releasing hormone may induce the release of EOP from the hypothalamus, which inhibit the HPT axis. This inhibition may be enhanced by a corticosteroid-induced decrease in testosterone feedback. PMID- 1882490 TI - Toxigenic Vibrio cholerae non-O:1 isolated from a goat in The Netherlands. AB - A case of enterotoxicosis in a goat at necropsy is described. The animal had died without clinical signs. Toxigenic Vibrio cholerae non-O:1 was isolated from the intestines. This species has not been reported earlier from healthy or diseased farm animals, such as goats, in the Netherlands. PMID- 1882491 TI - Prevalence of Leptospira interrogans serovar hardjo antibodies in milk in Belgian dairy herds. AB - Pooled milk samples were collected from 2000 Belgian dairy herds in the autumn of 1989. Antibodies against Leptospira interrogans serovar hardjo were detected in 9.2% of the herds, with the incidence being higher in the southern part of the country. PMID- 1882492 TI - Dysphagia in Bouviers associated with muscular dystrophy; evaluation of 24 cases. AB - Twenty-four Bouviers with dysphagia were examined between October 1986 and October 1988. The type of dysphagia was characterised by the results from the clinical examination, the videofluorographic examination and the electromyographic recordings from the oral, pharyngeal, and esophageal muscles. Electromyography indicated neurogenic as well as myogenic causes of dysphagia. Tissues from 10 dogs were available for histopathologic examination. In nine dogs there was a progressive muscular degeneration of the pharyngeal and/or esophageal muscles, resembling muscular dystrophy. In two of these dogs the same abnormalities were also noticed in the masseter and temporalis muscles and in the intrinsic laryngeal muscles. In one dog small areas with hyalin degeneration and fragmentation of muscle fibres were found in the cricopharyngeal muscle. No abnormalities in nerve tissue were found. Muscular dystrophy is a hereditary disease. The mode of transmission in these Bouviers is not yet known. PMID- 1882493 TI - Predictability of post mortem abnormalities in shipments of slaughter pigs as an aid for meat inspection. AB - This paper reports on the predictability of post mortem abnormalities in individual deliveries of pigs, shipped from the fattening herd to the slaughterhouse. The percentage of pigs in a delivery having post mortem abnormalities was expressed in a Meat Inspection Index. This index is based on data about relevant abnormalities, weighted on the specific significance of each for meat inspection. It was investigated whether Meat Inspection Indices of previous deliveries of pigs could be used for prediction of indices of future deliveries. Results suggest that the Meat Inspection Index cannot be used in such a predictive capacity, partly because of great variation among individual shipments. However, a Meat Inspection Index could play a role in signalling farms that are likely to deliver pigs with a higher level of abnormalities. More attention could then be paid to animals coming from these herds. PMID- 1882494 TI - Pharmacokinetics of sulphadimidine in carp (Cyprinus carpio L.) and rainbow trout (Salmo gairdneri Richardson) acclimated at two different temperature levels. AB - The influence of temperature (10 degrees C and 20 degrees C) on pharmacokinetics and metabolism of sulphadimidine (SDM) in carp and trout was studied. At 20 degrees C a significantly lower level of distribution (Vdarea) and a significantly shorter elimination half-life (T(1/2)beta) was achieved in both species compared to the 10 degrees C level. In carp the body clearance parameter (ClB(SDM)) was significantly higher at 20 degrees C compared to the value at 10 degrees C, whereas for trout this parameter was in the same order of magnitude for both temperatures. N4-acetylsulphadimidine (N4-SDM) was the main metabolite of SDM in both species at the two temperature levels. The relative N4-SDM plasma percentage in carp was significantly higher at 20 degrees C than at 10 degrees C, whereas there was in trout no significant difference. In neither species was the peak plasma concentration of N4-SDM (Cmax(N4-SDM)) significantly different at two temperatures. The corresponding peak time of this metabolite (Tmax(N4-SDM)) was significantly shorter at 20 degrees C compared to 10 degrees C in both carp and trout. In carp at both temperatures, acetylation occurs to a greater extent than hydroxylation. Only the 6-hydroxymethyl-metabolite (SCH2OH) was detected in carp, at a significant different level at the two temperatures. Concentrations of hydroxy metabolites in trout were at the detection level of the HPLC-method (0.02 micrograms/ml). The glucuronide metabolite (SOH-gluc.) was not detected in either species at the two temperatures. PMID- 1882495 TI - The course of experimental Trypanosoma vivax infection in Uda sheep. AB - The course of experimental Trypanosoma vivax infection in eight Uda rams was studied. All the infected animals became parasitaemic 2 days post-inoculation and remained so throughout the study period. A three-phase disease pattern was recognized, i.e. acute, subacute and chronic stages lasting 17-85 days. The disease was characterized by fever and a terminal decrease in rectal temperature despite an increase in parasitaemia with time for rams with acute and subacute infections. Mean weight loss was most marked in subacute followed by chronic cases. Gross pathological changes observed in some infected rams with subacute and chronic trypanosomosis were oedema of the face and lower jaw, hydropericardium and atrophy of the pericardial fat. Petechial haemorrhages were observed on the surfaces of the heart and kidney of rams with acute infection. Anaemia was most severe in infected rams with acute disease, followed by those with subacute infections. Also, hypoproteinaemia was observed in all infected rams. Severe clinical findings associated with the death of all the infected rams during this study might indicate that the Uda breed of sheep in very susceptible to trypanosomosis. It is, therefore, recommended that this breed of sheep, which is strictly bred and reared in tsetse-free Sahel savannah, should not be introduced into endemic areas devoid of therapeutic cover and strict tsetse fly control. PMID- 1882496 TI - Warble development by the rodent bot Cuterebra fontinella (Diptera: Cuterebridae) in the deer mouse. AB - Warbles induced by the rodent bot fly larvae, Cuterebra fontinella, developed over a period of 3.5-4 weeks in the deer mouse Peromyscus maniculatus. Warble location, structure and dynamics were examined. Clustering of warbles occurred primarily within the inguinal region of the deer mouse with a significant number favoring the area between the anus and genital organ. No differences in warble production were found in hosts of either sex. On two occasions, a warble was encountered forming directly in the genitals. Warble structure consisted of a pore, cavity and capsule, all of which changed in shape and size as the larvae grew. A new pore was formed during the first larval molt and was commonly bordered by a yellowish precipitate. A bi-layered warble capsule surrounded the cavity as a thin layer and a thick diffuse outer layer. The growing warble expanded into the subcutaneous tissue of the inguinal area and stretched the hide caudally. Subcutaneous tissue surrounding developing warbles became relegated to small areas, leaving only a thin muscle to separate the warble from the peritoneum. Widening of the pore at the time of larval emergence is described. Linear relationships are given describing warble growth and pore enlargement as a factor of time. The location of warbles and the morphology of the pore are discussed in relationship to larval protection. Damage to the host due to warble formation is also addressed. PMID- 1882498 TI - Resistance of restrained Bos taurus dairy bull calves to the bont tick Amblyomma hebraeum (Acarina: Ixodidae). AB - Three infestations of restrained Jersey and Friesland bull calves with adult Amblyomma hebraeum did not affect the rate of engorgement of female ticks and resulted in an insignificant decline in the mean engorgement weight of female ticks recovered from the Friesland group. Repeated infestations significantly affected the egg-laying capacity of engorged female ticks recovered from both groups of hosts. The Friesland calves manifested an enhanced resistance to the larvae and nymphs of Amblyomma hebraeum resulting in prolonged attachment, and a significant decline in engorgement rate of these instars compared with the Jersey group. Skin reaction tests using crude tick extracts yielded antigen-specific hypersensitivity reactions which were not related to resistance to A. hebraeum. Histological changes at the attachment site associated with tick rejection are discussed in relation to host resistance mechanisms. PMID- 1882497 TI - Acquired immunity to Toxocara canis infection in mice. AB - Acquired immunity develops against Toxocara canis infection in mice, and NIH mice are more immunoresponsive than CD1 mice. Twice infected NIH female mice showed 27% reduction in the total larval recoveries compared with non-sensitized controls. Twice-infected NIH male, and CD1 (both sexes) mice showed a negligible reduction in the total recoveries, though a significant (P less than 0.05) number of larvae were retained in the liver compared with the non-sensitized controls. All twice-infected mice showed a significant reduction in the number of larvae recovered from the brain compared with once-infected mice. Vaccination using ultraviolet irradiated embryonated eggs gave the best protection against reinfection. Excretory/secretory antigen afforded less protection, whilst whole adult worm vaccine and whole L2 culture vaccine gave no protection. Vaccinated mice had a higher 'free:penetrating ratio' of larvae in their intestine than similarly challenged but non-vaccinated mice. When the ileum was examined histologically 9 h post-infection, an inflammatory reaction was seen around the penetrating larvae in the sensitized and vaccinated mice but not in untreated controls, suggesting a role played by the intestine in the resistance against T. canis infection in mice. PMID- 1882499 TI - Acaricidal activity of kupetaba, a ground mixture of natural products, against Rhipicephalus appendiculatus. AB - Eight substances were screened for the purpose of selecting a natural product as an acaricide for use within an integrated tick management system. One substance proved to be effective as an acaricide against all stages of Rhipicephalus appendiculatus and was named 'kupetaba'. It is a ground mixture of dried tobacco leaves (family Solanaceae) and a mineral called 'Magadi soda' which is mined around Lake Magadi in the Rift Valley province of Kenya. Investigation showed that kupetaba is commonly sold in local markets in East, West and Central Africa, where it is used for many purposes. The substance prevented the completion of all feeding phases of the tick, suppressed the oviposition capacity of the engorged ticks and drastically reduced the hatchability of the eggs. Larvae and nymphs were killed within 24 h of the application of the substance on calves' ears, while large numbers of adult ticks were also killed within 2-3 days of application during in vitro experiments. The suitability of the natural product as a local acaricide which resource-poor farmers in Africa can use to replace commercial acaricides within an integrated tick management system is discussed. PMID- 1882500 TI - Presence of bovine theileriosis in Saudi Arabia. PMID- 1882501 TI - Experimental Isospora suis infections in miniature swine. AB - Clinical responses to experimental Isospora suis infections were compared in Sinclair miniature pigs and cross-bred conventional pigs. Pre-patent periods, fecal consistencies, oocyst excretion dynamics, trends in surviving pig weights and lesions were similar in infected miniature and conventional pigs. The results indicate that the susceptibility of miniature pigs to I. suis is similar to that of conventional pigs. These findings should encourage their use as models for the study of neonatal coccidiosis. PMID- 1882502 TI - Helminths of guinea fowl (Numida meleagris) in Bashkir ASSR. AB - Guinea fowl from different regions of Bashkir Autonomous Soviet Socialist Republic (BASSR) were examined for helminths. Of the 547 fowl examined, 451 (82.4%) harboured at least one species of helminth. A total of 56,772 helminths were collected and classified. Of this number seven were found to be trematodes, 25 cestodes and 56,740 nematodes. Five species of helminths were identified. Amongst infected birds, trematodes were present in three (0.7%), cestodes in eight (1.8%) and nematodes in 451 (100%). Of all recorded helminths, the incidence of Heterakis gallinarum (Gmelin, 1790) was highest. Pre-patent periods for seven species of trematodes were observed in guinea fowl for the first time. PMID- 1882503 TI - Differences in sensitivity in haemagglutinin inhibition assays between A/equine/H3N8 viruses isolated in eggs and MDCK cells are linked to cleavage of the haemagglutinin molecule. AB - Two primary isolates of A/equine/H3N8 viruses were obtained in embryonated hens' eggs and in Madin-Darby canine kidney (MDCK) cells. Viruses isolated in MDCK cells were significantly more sensitive as antigens in haemagglutination inhibition (HI) tests. This sensitivity appeared to be primarily linked to the extent of cleavage of the haemagglutinin molecule. PMID- 1882504 TI - Isolation of exfoliative toxin from Staphylococcus hyicus subsp. hyicus and its exfoliative activity in the piglet. AB - Exfoliative toxin was isolated from the sterile cell-free filtrate of 24 h culture of Staphylococcus hyicus subsp. hyicus strain P-1. The partial purification of exfoliative toxin produced by S. hyicus (shET) was performed by precipitation with 50-80% saturated ammonium sulfate, gel filtration on a Sephadex G-75 column and column chromatography on DEAE-cellulose. Partially purified shET (pp-shET) caused exfoliation in piglets at 8 to 12 h after intradermal or subcutaneous injection. However, heat-treated pp-shET did not cause exfoliation in piglets for up to 24 h after injection. On histopathological examination of the skin at 12 h after injection of pp-shET, an intraepidermal cleavage plane was shown between the stratum corneum and stratum granulosum and at the stratum granulosum. PMID- 1882505 TI - Antibody to Pseudomonas pseudomallei exotoxin in sheep exposed to natural infection. AB - Specific antibody to Pseudomonas pseudomallei exotoxin was detected in sheep sera exposed to natural infection. An enzyme-linked immunosorbent assay (ELISA) was used. Serum antitoxin was present in 49.3% of sera obtained from a flock of sheep naturally exposed to P. pseudomallei infection. Among these sera, 17.0% gave titers of 10,000. In contrast, serum antitoxin was present in only 6.0% of sera collected from sheep kept on a melioidosis-free farm. The ELISA reactivity of all positive sera could be completely absorbed with purified P. pseudomallei exotoxin. Similarly, preincubation of the exotoxin-coated wells with specific antiserum inhibited the ELISA reactivity of sheep sera. The results indicate that exotoxin is produced in vivo during infection by P. pseudomallei. PMID- 1882507 TI - Protection against murine potomac horse fever by an inactivated Ehrlichia risticii vaccine. AB - Ehrlichia risticii propagated in a murine macrophage cell line were freed from the host cell by hypotonic lysis of the infected cells. The cell-free ehrlichiae were inactivated with beta-propiolactone and combined or not combined with polymyxin-B. The vaccines were administered to mice with Quil-A (saponin) as an adjuvant twice at 2 to 3 week intervals and the mice were challenged with live E. risticii 2 to 3 weeks after the last vaccination. With or without the addition of polymyxin-B, the vaccine preparations protected mice from developing clinical signs and gross pathologic changes such as thymic atrophy, splenomegaly, and increase in whole intestinal weight. Mice vaccinated with or without polymyxin-B developed high titer IgG antibody against E. risticii before and after the challenge with live E. risticii. Spleen lymphocyte proliferative response assay at 11 days post challenge revealed that with polymyxin-B a higher lymphocyte proliferation occurred as compared with that of the mice which received polymyxin B-free vaccine. Spleen lymphocytes of the placebo (polymyxin-B and Quil-A) pretreated/challenged mice showed no proliferative activity. Western blot analysis revealed that vaccinated mice reacted mainly with 110, 57 and 33 kDa antigen bands before and after challenge. The placebo (polymyxin-B and Quil A)/challenged mice showed a very weak response to ehrlichial antigens at day 10 to 11 post challenge. Comparison with inactivated Renografin-purified E. risticii or 0.25% SDS-insoluble fraction of E. risticii with the inactivated host cell free vaccine revealed no increased protection. These results indicate that inactivated host cell-free E. risticii can protect mice from murine Potomac horse fever. The presence of polymyxin-B appeared to be not harmful but rather beneficial for lymphocyte proliferation response upon challenge with live E. risticii. PMID- 1882506 TI - Immune responses in chickens against Salmonella typhimurium monitored with egg antibodies. AB - Three mature hens were immunized with an Aro- mutant of Salmonella typhimurium beginning with a subcutaneous dose in adjuvant followed by two oral boosters. Isotype-specific antibodies were measured in the white and yolk eggs collected weekly over a period of 230 days. Two hens showed a memory response to the first oral booster, with large increases in egg yolk IgG and smaller increases in IgA and IgM antibodies in egg whites. Smaller amounts of IgA and IgM antibodies were found in egg yolks, and a slight increase in IgG occurred in the whites. One hen showed an increase in serum titers of all isotypes against S. typhimurium. The second hen had high serum titers before immunization was started which did not change. The third hen had a high level of IgM in the white of eggs before immunization was started. This hen showed erratic responses in egg white antibodies following immunization, no increase in IgA or IgM in yolks and only a slight increase in IgG, no increase in serum IgG, and was the only hen with a high level of IgM antibody against S. typhimurium in the bile, conditions reflecting a state of oral tolerance. With the exception of this hen, the results showed that IgA and IgM antibodies were aroused in hens by immunization with an avirulent mutant of S. typhimurium, and that these antibodies were present in the white of eggs from immunized hens. PMID- 1882508 TI - Enhanced virulence of Staphylococcus aureus from bovine mastitis induced by growth in milk whey. AB - The virulence towards mice of Staphylococcus aureus strains from bovine mastitis was enhanced upon growth in milk whey compared to homologous organisms grown in tryptic soy broth (TSB). In the mouse mastitis model, S. aureus grown in milk whey caused more severe lesions than homologous strains grown in TSB. Staphylococcus aureus strain F1440 grown in milk whey induced 75% mortality and local necrotic reaction in subcutaneously inoculated mice, whereas the homologous strain grown in TSB caused only 5% mortality and slight skin reaction. Extracellular capsule on milk whey-grown, S. aureus could not be demonstrated. However, diffuse type colony morphology could be correlated with an increased virulence of S. aureus towards mice. PMID- 1882509 TI - Absence of mouse-lethal toxins in Australian isolates of Bordetella avium. AB - A total of 18 Australian isolates of Bordetella avium and seven reference B. avium strains from Europe and the USA were tested for the presence of a mouse lethal toxin. Five of the seven reference strains of B. avium, but none of the 18 Australian isolates, produced the toxin. PMID- 1882510 TI - Biochemical typing of Actinobacillus pleuropneumoniae. AB - A study was conducted to evaluate the possibility of using biochemical differences among strains of a given serotype of Actinobacillus pleuropneumoniae as epidemiological markers, to rapidly identify the source of infection in herds affected with swine pleuropneumonia. Out of 38 different biochemical and physiological tests performed on a total of 67 strains belonging to serotypes 1 and 5 of A. pleuropneumoniae, three fermentation tests, glycerol, lactose and raffinose, allowed the classification of serotype 1 strains into 6 phenotypic groups and serotype 5 strains into 4 of these groups. Groups II and III were exclusively composed of serotype 1 strains, whereas the majority of strains in groups I and IV belonged to serotypes 1 and 5 respectively, the latter comprising almost all the serotype 5 studied. PMID- 1882512 TI - The effect of repeated abdominocentesis on peritoneal fluid constituents in the horse. PMID- 1882511 TI - The kinetics of inflammation and phagocytosis during bovine mastitis induced by Streptococcus agalactiae bearing the protein X. AB - The protein X of Streptococcus agalactiae is a surface antigen borne by a high proportion of strains isolated from bovine mastitis. We have tested the capacity of two strains of X-bearing Streptococcus agalactiae to induce mastitis in dairy cows. The reference X-strain (411.07) produced an intramammary infection with local clinical signs in the three inoculated quarters. Another X-bearing strain (443.31) of bovine origin produced infection in all 11 quarters inoculated with only 25 or 85 colony-forming units. In naive cows, strain 433.31 induced less exudation of plasma into the milk, shedding of bacteria, macroscopic alteration, and a lower somatic cell count (SCC) than did the reference strain. Only one quarter spontaneously eliminated the infection before antibiotic treatment 9 days after inoculation. The serum of all the cows contained naturally acquired or induced antibodies to the challenge strain (443.31) and possessed opsonic activity. Before inflammation occurred, the milk was almost devoid of antibody or opsonic activities. The early phase of infection was characterized by rapid multiplication of streptococci in the milk, followed by a sharp drop in bacterial counts concomitant with the onset of inflammation. Three cows immunized with protein X displayed higher SCC and bactericidal activity in milk from the inoculated quarter at the onset of inflammation than non-immunized cows. Two of the three immunized cows underwent an early and transient febrile episode and eliminated the infection. PMID- 1882513 TI - The effects of stressful exercise on leukocytes in cattle with experimental pneumonic pasteurellosis. AB - Seven yearling bulls were treated with stressful exercise and intrabronchial Pasteurella haemolytica A1. Group 1 bulls (nos. 1-4) underwent treadmill exercise and, 24 days later, intrabronchial instillation of P. haemolytica A1. Group 2 bulls (nos. 5-7) underwent treadmill exercise, followed 30 min later by intrabronchial P. haemolytica A1. Blood lactic acid values were raised (p less than 0.05) by treadmill exercise only, but plasma cortisol was raised (p less than 0.05) by treadmill exercise and by P. haemolytica A1 infection. Neutrophils in bronchoalveolar lavage (BAL) differed from control values 24 h after treadmill exercise, and 1 h and 4 h after P. haemolytica A1 infection. Respiratory disease was more severe and the gross lung lesions were larger in group 2 bulls than in group 1 bulls. P. haemolytica A1 was recovered from the livers, spleens and mesenteric lymph nodes of group 2 but not group 1 bulls, suggesting that group 2 bulls had experienced bacteraemia. Decreased neutrophils in BAL fluid from group 2 bulls at 1 h and 4 h after infection suggests that exercise transiently inhibited neutrophil egress from the blood to the alveoli; BAL neutrophils peaked at 1 h and 4 h after infection in group 1 bulls but declined at 24 h. We conclude that group 2 bulls were made more susceptible to experimental pneumonic pasteurellosis by stressful exercise. PMID- 1882514 TI - An ultrastructural study on the pancreatic islet B cells in diabetic herbivorous voles. AB - An ultrastructural study was performed on the pancreatic islet cells of normal herbivorous voles and of voles in which diet-induced diabetes had been induced by feeding a low-fibre, high-concentrate diet. Examination of the pancreatic islet cells revealed degranulation and a well-developed Golgi apparatus and rough endoplasmic reticulum in the B cells of the slightly diabetic voles showing moderate hyperglycaemia and hyperinsulinaemia, and markedly degenerative B cells with almost complete absence of secretory granules in the severely diabetic voles showing marked hyperglycaemia and hypoinsulinaemia. These results indicate that the pancreatic B cells had become hyperfunctional so that insulin secretion was increased in the slightly diabetic voles; thereafter the B cells degenerated rapidly and the voles fell into insulin deficiency. PMID- 1882516 TI - Endotoxin in the conscious piglet: its effects on some general and gastrointestinal myoelectrical parameters. AB - The effect of an intravenous bolus injection of endotoxin, 0.1, 1 or 10 micrograms/kg, on rectal temperature, clinical appearance, haematological parameters, and on gastrointestinal electrical activity was examined in 11 conscious piglets of 4-5 weeks of age, with implanted electrodes in the antrum pylori, duodenum, jejunum and ileum. All doses resulted in a significant and dose dependent increase in rectal temperature, in pronounced clinical signs and in distinct changes in haematological values. These included shivering, depression, respiratory distress, a leukopenia (0.1 micrograms/kg) or a leukocytosis (1 microgram/kg) with a shift to the left, an accelerated sedimentation rate and a decreased packed cell volume. Doses of 1 and 10 micrograms/kg induced a transient inhibition of gastroduodenal electrical activity. These results suggest that, in the piglet, endotoxin primarily manifests general clinical signs and that the gastrointestinal effects coincide with these. PMID- 1882517 TI - [The selection of cold-adapted variants of the influenza viruses H1N1 and H3N2 and their antigenic and genetic characteristics]. AB - As a result of serial passages (42 passages) at low temperatures (26 degrees--28 degrees C) of two influenza H1N1 and H3N2 virus strains stable cold-adapted (ca) variants were produced. Investigations of them showed the ca A/USSR/03/84 (H1N1) variant to have ts-mutations in genes 1, 2, 4, 5, 7, and 8 and the ca A/USSR/215/79 (H3N2) to have ts-mutations in genes 1, 3, 4, 5, 7 and 8. These ca variants may be recommended as attenuation donors to be used in recombination experiments with epidemic influenza viruses in order to obtain attenuated reassortant candidate vaccine strains. PMID- 1882518 TI - [The acceleration of experimental influenza B infection under the influence of gangliosides]. AB - The influence of mono-, di-, and trisialogangliosides on the dynamics of influenza B virus reproduction in human embryo fibroblast (HEF) cell culture and human diploid cells was established. The cells were treated with neuraminidase of non-cholera vibrio for removal of natural receptors followed by treatment with gangliosides. Virus reproduction was assessed by infectious titres for chick embryos and HA test of the culture fluid at certain intervals. Gangliosides restored influenza virus reception and enhanced the infectious process as compared with the controls. Treatment with gangliosides of HEF culture of low sensitivity increased its susceptibility to virus markedly. PMID- 1882515 TI - A review of the pathophysiology of exercise-induced pulmonary haemorrhage in the equine athlete. AB - In the United States, more than 75% of equine athletes are reported to suffer from exercise-related haemorrhage of the respiratory tract (Voynick and Sweeney, 1986; Sweeney et al., 1990). Fiberoptic endoscopy has traced the source of blood to beyond the bifurcation of the trachea. In 1981, the term exercise-induced pulmonary haemorrhage (EIPH) was introduced (Pascoe et al., 1981). Racehorses of all breeds, polo ponies and three-day event horses of mixed heritage, even foxhunters, may 'bleed' (Voynick and Sweeney, 1986; Pascoe et al., 1981; Sweeney and Soma, 1983; Hillidge, 1986). Any horse working at speeds greater than 240 m/min is at risk (Voynick and Sweeney, 1986). The impact of exercise-induced pulmonary haemorrhage is difficult to assess. Most attempts to demonstrate statistically a negative correlation between EIPH and performance have been unrewarding, largely due to the number of uncontrollable variables (Pascoe et al., 1981; Raphel and Soma, 1982). In racing thoroughbreds (Mason et al., 1983) and standard breeds (MacNamara et al., 1990) approximately half as many EIPH positive as EIPH-negative horses were placed in their races. Based on extensive intrapulmonary haemorrhage, a 3-year prospective study of sudden deaths in exercising thoroughbreds concluded that 9 out of 11 deaths were attributable to EIPH (Gunson et al., 1988). By correlation of clinical signs, thoracic radiographs, ventilation/perfusion scintigraphy, gross and subgross pathology and histopathology in 26 affected thoroughbreds, EIPH has been associated with chronic small airway inflammation, proliferation of subpleural, peribronchial and septal bronchial arterioles, interstitial connective tissue fibrosis and alveolar septal disruption in the dorsocaudal lung lobes (O'Callaghan et al., 1987). From this work it was proposed that the initial insult of EIPH started as focal, dorsocaudal pulmonary peribronchial inflammation which resulted in bronchial arterial neovascularization. Haemorrhage then occurred when, during exercise, bronchial blood pressure increased in fragile capillary buds. The incidence of bronchitis/bronchiolitis, regardless of aetiology, has been estimated to be 30% in non-racing equine athletes and close to 100% in one group of racing thoroughbreds (Sweeney et al., 1989). Histological study of lungs from horses with mild, moderate and severe chronic small airway disease consistently revealed a greater density of lesions in the diaphragmatic lobes (Winder and von Fellenberg, 1988). To understand further the aetiology and/or pathophysiology of EIPH, we will first explore some aspects of general mammalian and specific equine pulmonary and bronchial vascular anatomy and physiology. Exercise-related changes in these systems in normal and EIPH-positive horses will be briefly reviewed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1882519 TI - [The expression of a fragment of the HIV-1 env gene in the cells of Escherichia coli bacteria]. AB - A recombinant plasmid pEK6 determining the synthesis of a hybrid protein the N terminus of which was represented by full-size beta-galactosidase and C-terminus by HIV-1 gene env virus-specific sequence was constructed. The analysis of lysates of E. coli HB101/pEK6 bacteria in 6% PAAGE revealed additional proteins with molecular weights from 185 to 130 kDa. These proteins interacted with blood serum antibodies of a virus carrier but formed no specific bands with sera from normal donors. Densitometric analysis of polyacrylamide gels stained with Coomassi R250 demonstrated that the level of production of recombinant protein was at least 15% of the total cell protein. Hybrid polypeptides formed poorly soluble inclusion bodies in the bacterial cells. Study of the immunological properties of the recombinant polypeptides showed that immunization of rabbits with these proteins induced antibodies specifically reacting with viral polypeptides with molecular weights of about 82 and 140 kDa. Such features as a high level of synthesis, technologically feasible purification of inclusion bodies, and adequate antigenic properties recommend this preparation for use in the development of diagnostic test systems. PMID- 1882520 TI - [The isolation and characteristics of continuous virus-producing lymphoid suspension cultures of African green monkey cells]. AB - Five continuous lymphoid suspension cell cultures were established by cultivation of lymphocytes from African green monkeys. The immunological typing revealed the mixed pattern of cultures consisting of B and T cell types. Two types of viruses: herpesvirus and retrovirus C-type were demonstrated by electron microscopy. Indirect immunofluorescence and molecular hybridization studies showed one of the viruses to be an EBV-related herpesvirus of green monkeys designated HVGM and the other to belong to H (S) TLV-1 group. PMID- 1882521 TI - [The membranotropic and neurotropic properties of remantadine and deitiforin in experimental models]. AB - The specific neurotropic action of rimantadine was demonstrated in mollusk neuron experiments. No specific neurotropic activity of dejtiphorin was found. In combined application, the latter blocked the neurotropic effect of rimantadine. In experiments in white mice and rats, high doses of both drugs decreased the emotional and motor activity of the animals. After the use of the combination of the two drugs the activity of the animals did not differ significantly from that in the controls. The antiviral effect of each drug alone and of combination thereof was similar. PMID- 1882522 TI - [The isolation and characteristics of reassortants between the Lassa and Mopeia arenaviruses]. AB - Reassortants with a mixed phenotype were produced by combined inoculation of Vero cells with Lassa and Mopeya viruses. These reassortants produced small plaques (Mopeya virus phenotype) and were not pathogenic for newborn mice (Lassa virus phenotype). The genotype of the reassortants was studied by dot hybridization experiments on filters using cDNA-probes differentiating genome segments of these viruses. The reassortants were shown to have Mopeya virus L-RNA and Lassa virus S RNA. PMID- 1882523 TI - [Experimental Lassa fever in hamadryas baboons]. AB - Intramuscular or aerogenic inoculation of baboons with Lassa virus reproduced a severe form of the disease which clinically, pathoanatomically and virologically resembles the severe form of human Lassa fever reported in the literature. The severity of monkey infection is demonstrated by rapid development of symptoms of general toxicity in the presence of fever, manifestations of hemorrhagic diathesis, high level of viremia and isolation of the causative agent from nasopharyngeal washings. PMID- 1882525 TI - [The use of the immunofluorescence method for the rapid diagnosis of influenza during 1968-1988 in Bulgaria]. PMID- 1882524 TI - [The action of UV irradiation on the reproduction of the influenza A virus and on virion RNA-polymerase activity]. PMID- 1882526 TI - [HTLV-I-associated hemoblastoses in different regions of the USSR]. PMID- 1882527 TI - [The differential etiological diagnosis of viral intestinal infection in newborn infants with a diarrheic syndrome]. PMID- 1882528 TI - [The experimental evaluation of the toxicity of virazole and ribamidil in vivo]. PMID- 1882529 TI - [The standardization of a method for determining virus-neutralizing antibodies to arboviruses]. PMID- 1882530 TI - [The problem of selecting a taxonomic rank in classifying viruses]. PMID- 1882531 TI - [The polymerase chain reaction]. PMID- 1882533 TI - [Disorders of the immune status in patients with acute diffuse peritonitis]. AB - Analysis of various parameters of the immune system and non-specific resistance in patients with acute generalized peritonitis (AGP) has indicated that in AGP there is immunodeficiency involving all the links of immune defense and non specific resistance. The T-cell immunity, primarily T helpers, is afflicted in AGP to the greatest extent. A magnitude of decreases in T helper counts may be used as a prognostic indicator in AGP. The severity of immune defense abnormalities correlates with the duration and intensity of intoxication, there is a "paralysis" of this defense in the terminal stage of AGP. PMID- 1882532 TI - [Mutations in the genes coding for hemagglutinin and neuraminidase in cold adapted variants of the influenza virus A/Leningrad/134/57 (H2N2)]. AB - An analysis of ts-mutations in the genomes of native and cold-adapted variants of influenza A/Leningrad/134/57 (H2N2) virus based on the use of fowl plague virus ts mutants was carried out. The recombination test was done by the conventional method in chick embryo fibroblast culture (genes PB2, PB1, PA, NP, NA, M and NS) or cell systems permissive for reproduction of human influenza virus (gene HA). The cold-adapted strain A/Len/17 used for preparation of live influenza vaccine (LIV) for adults was shown to have 4 ts mutations: three in "internal" genes (PB2, NP, and M) and one in gene 4 coding for hemagglutinin (HA). The more attenuated cold-adapted donor A/Len/47 for preparation of similar LIV for children acquired three additional ts mutations: two (PB1 and NS) in "internal" genes and one in gene 6 coding for neuraminidase (NA). The accumulation of ts mutations in the genome of cold-adapter strains was found to be accompanied by a decrease in their pneumotropicity for mice as well as their detectability in different organs of these animals. PMID- 1882534 TI - [Ultraviolet irradiation of the blood in the treatment of pyo-inflammatory complications in patients with terminal renal failure]. AB - The authors describe a technique of extracorporeal UV radiation of blood (EUVRB) in flow closed circulation. Its efficacy was assessed in combined treatment of pyo-inflammatory complications of terminal renal failure. Therapeutic effects of EUVRB are due to reduced endogenic intoxication, correction of leukopoiesis and stimulation of immunity. The changes in laboratory findings correlated with clinical pattern of the inflammation. EUVRB produced a favourable response and improved therapeutic results of pyo-inflammation treatment in patients with terminal renal failure. PMID- 1882535 TI - [The prevention of suppuration of postoperative wounds]. AB - A method to prevent operative wound suppuration is offered. An experimental animal model of operative wound suppuration was elaborated to specify rational antibiotic-antiseptic prophylaxis and adequate wound drainage. This yielded a complex of measures to prevent purulent complications on the part of the operative wound. In addition, an original turbidimetric technique to assess the resistance of the biological fluid microflora to antisepsis was elaborated. The complex prophylaxis against suppuration of infected wounds was clinically tested on 124 patients operated on for different acute surgical conditions of abdominal organs. The wound process was controlled by means of an original endoscopic bacteriologic technique. The postoperative period was complicated by the wound suppuration in two of the 124 patients (1.6 per cent). The postoperative hospital stay in most cases lasted 5-7 days. PMID- 1882536 TI - [Primary pulmonary hypertension]. AB - Primary pulmonary hypertension is a progressive disease of an unknown etiology which attacks mainly young people. Metabolic disturbances of biologically active substances produced in the endotheliocytes of pulmonary vessels play the leading role in pathogenesis of the disease. They result in structural changes of the vessels wall. In spite of the variety of the morphologic changes the clinical picture of the disease is generally common. A great variety of invasive and noninvasive investigations is necessary for verification of the diagnosis. Chemotherapy fails to stop the disease progress, though the main parameters of central hemodynamics are improved under the influence of vasodilators. Foreign investigators believe heart-lung transplantation to be radical treatment of patients suffering from primary pulmonary hypertension. PMID- 1882537 TI - [The treatment of atherosclerosis and hypertension using extracorporeal therapy methods]. AB - Extracorporeal techniques (hemosorption, plasmapheresis, thrombocytoplasmapheresis, quantum hemotherapy) were studied for their impact on the clinical course of a disease and some hemostatic parameters in 370 patients with cardiovascular diseases (coronary heart disease, hypertensive disease, lower extremity at atherosclerosis obliterans). They were found to be effective in managing patients with atherosclerosis and arterial hypertension who are refractory to the conventional drug therapy. When there was a positive clinical action of therapy, the patients with coronary heart disease were demonstrated to show better parameters of lipid metabolism, immunological status and blood aggregation control system. The hypotensive effect of plasmapheresis in patients with arterial hypertension was followed by a decrease in pressor hormone levels and peripheral vasodilatation. PMID- 1882538 TI - [Phosphocreatine, tocopheryl phosphate and their combination in acute ischemia and myocardial reperfusion in dogs: the effect on rhythm disorders, left ventricle contractility and infarct size]. AB - The effects of phosphocreatine and tocopheryl phosphate and their combined use in ischemia and reperfusion of the heart were studied in anesthetized dogs. The investigation focused on the size of myocardial infarction and left ventricular contractility, ischemic and reperfusion arrhythmias were assessed using Holter monitoring. Phosphocreatine was found to reduce the number of arrhythmias and to prevent the fatal outcomes in myocardial ischemia animals but not to influence the reperfusion rhythm disturbances. Combined administration of tocopheryl phosphate and phosphocreatine, in contrast to their isolated use, completely prevented the development of ventricular fibrillations and fatal outcomes in the animals with reconstructed coronary flow. Administration of phosphocreatine restricted the infarction size, combined use of the drugs facilitated its further reduction, while the group with isolated administration of tocopheryl phosphate showed the infarction size to differ insignificantly from the control values. Combined administration of the drugs, unlike their use alone, improved left ventricular contractility in reperfusion of ischemic myocardium. The cardioprotective effect observed in combined administration of the drugs was attended with depressed lipid peroxidation in reperfused myocardium. PMID- 1882539 TI - [An emulsion of fluorocarbons as a protective agent against myocardial ischemia]. AB - Acute myocardial ischemia was induced by reducing the lumen of the anterior descending branch of the left coronary artery in 32 mongrel dogs. Following 60 min of ischemia, 16 animals were infused perfluorine carbon emulsion (10 ml/kg) and 16 were given saline. Alteration in hemodynamics, myocardial contractility, coronary blood flow, as well as pH and pO2 in the ischemic area were examined. The analysis of the results showed that carbon tetrafluoride emulsion, in contrast to saline, substantially increased coronary blood flow and oxygen supply in the ischemic area decreased myocardial ischemic and reperfusion lesion, improved hemodynamic parameters and myocardial contractility. PMID- 1882540 TI - [The transport of monovalent ions and calcium in the erythrocytes of patients with bronchial asthma]. AB - The intracellular levels of sodium, potassium, and free calcium, as well as red blood cell transport of 86Rb (a radioactive potassium analogue) and 45Ca were measured in patients with bronchial asthma (BA). The intracellular content of sodium was 10-20% higher in patients with BA, though the differences in the present sample (7 controls and 18 BA patients) failed to be significant (p less than 0.05). The differences were most pronounced in infection-dependent BA and not eliminated during glucocorticoid hormone therapy. The activity of the Na+, K+ pump, as assessed by the values of an ouabain-inhibited component of 86Rb entry, was increased by 10-20% (p less than 0.05) in BA patients and of Na+, K+ cotransport (an ouabain-sensitive furosemide-inhibited component of 86Rb entry), by 35-45% (p less than 0.25). The passive red blood cell membrane permeability in BA patients (an ouabain + furosemide-insensitive component of 86Rb) remained unchanged. The quin-2-loaded red blood cell entry rate for 45Ca was decreased by 5-10%. In the absence of a Ca(2+)-ATPase inhibitor (0.5 mM orthovanadate), these differences were greatly significant (p less than 0.005). In addition, the patients with BA showed a 10% reduction in free calcium levels; however, the differences were insignificant (p less than 0.25), which might be caused by Ca pump activation. As in the experiments with Na+ level measurements, the greatest differences in red blood cell Ca(2+)-balance control were recorded in patients with infection-dependent BA and independent of glucocorticoid hormone therapy. Possible mechanisms of involvement of the changes found in monovalent cation and Ca2+ transport in the pathogenesis of BA were also discussed. PMID- 1882541 TI - [Clinical immunodiagnosis]. AB - The paper represents a clinical interpretation of results obtained from immunological investigations, shows a differential reaction of the immune system to exo- and endogenous exposures, defines immunological parameters suitable for assessing health and for characterizing the environment, provides a clinicoimmunological reaction of white blood cells, establishes the mechanism of action of the factors of petrochemical enterprises on the immune system. PMID- 1882542 TI - [Pathogenetic principles of the diagnosis of chronic inflammation]. AB - The main attention in diagnosis of chronic exudative-destructive inflammation resulting from tissue injury should be focused on responsiveness and functional reserves of polymorphonuclear leukocytes (PML) from blood and lesion, the key effectors of inflammatory reaction. The ability of phagocytes to migrate into the lesion site and generate phlogogenic substances is to be analysed. Basing on the initial state of PML system and its functional limits one can predict the effectiveness of the treatment with antiinflammatory drugs and immunostimulators. In the diagnosis of mononuclear infiltrative inflammation the reliable assessment of macrophage responsiveness and their relations with lymphoid cells is of great importance. PMID- 1882543 TI - [The innovative process in public health institutions as mirrored by public opinion]. AB - Problems related to innovations in the health care system and the susceptibility of medico-prophylactic institutions to advanced methodologies are discussed. Analysis of questionnaires has revealed the absence of a well-organized work for the introduction of innovations in the medical collectives, and a low interest in their introduction and exploration on the part of physicians and their authorities. The innovative activity is high enough in regional health units, but in those dealing with mass-scale medical care, rural in particular, introduction of new methodologies is much slower. At the same time, collectives of medical workers show their potential readiness to accept and explore the new advanced methodologies, which has not been realized due to the poor economic basis, low organizational level, and deficient resources. Ways to improve the process of introduction of innovative methodologies into clinical practice are offered for discussion. PMID- 1882544 TI - [Immobilized antibodies in the extracorporeal detoxification of the body]. PMID- 1882545 TI - [Pathophysiology as a modern integrative biomedical science]. PMID- 1882547 TI - Increased endocytosis in the Saccharomyces cerevisiae fragile mutant VY1160. AB - The VY1160 mutant is characterized by cell lysis in hypotonic solutions and generally increased permeability to substances for which Saccharomyces cerevisiae cells are not permeable. Two mutations, srb1 and ts1, have been identified in VY1160 mutant, and previous studies (Kozhina et al., 1979) have shown srb1 to be responsible for cell lysis. We now present evidence that the ts1 mutation leads to increased endocytosis in VY1160 cells. The internalization of lucifer yellow carbohydrazide in VY1160 cells is time-, temperature- and energy-dependent and consistent with a fluid-phase mechanism of endocytosis. The rate of steady-state accumulation of the dye at 37 degrees C is 145 ng/micrograms DNA per h for VY1160 mutant and 23 ng/micrograms DNA per h for S288C parental strain. Studies with isogenic strains having either the srb1 or the ts1 mutation, or SRB1 TS1 wild type alleles have shown that only ts1 strains possess increased endocytosis. Quantitation of endocytosis in cells grown at 24 degrees C and shifted at 38 degrees C shows that ts1 strains, but not srb1 and wild-type strains, increase ten-fold the internalization of lucifer yellow 2 h after the shift at 38 degrees C. The analysis of ts1 x wild-type crosses provides evidence that the temperature sensitive phenotype segregates together with the enhanced endocytosis. It is concluded that the increased endocytosis might explain the generally increased permeability of VY1160 mutant cells. PMID- 1882546 TI - Biosynthesis and assembly of alcohol oxidase, a peroxisomal matrix protein in methylotrophic yeasts: a review. AB - Alcohol oxidase (AO) catalyses the first step of methanol metabolism in yeasts. In vivo the enzyme is compartmentalized in special cell compartments, called peroxisomes. The enzyme along with the organelles are induced during growth of methylotrophic yeasts on methanol as the sole carbon source. Like all other peroxisomal matrix proteins, AO is encoded by a nuclear gene. Expression of the protein is regulated by a repression/derepression mechanism, but also by induction. Inactive monomeric precursor protein is synthesized in the cytosol and subsequently imported post-translationally into peroxisomes without further processing. Assembly into the active homo-octameric enzyme and binding of the prosthetic group flavin adenine dinucleotide occurs inside the organelle. When enhanced concentration of octameric alcohol oxidase are present in the organelles, the enzyme may form a crystalloid. Oligomerization is not dependent on translocation of AO precursors into their target organelle since octameric, active AO is detected in the cytosol and nucleus of peroxisome-deficient mutants of Hansenula polymorpha: at high expression rates large cytosolic AO crystalloids are formed, which occasionally are also encountered inside the nucleus of such mutants. This paper summarizes recent findings and views on the mechanisms involved in synthesis, import, assembly and crystallization of this important peroxisomal enzyme. PMID- 1882548 TI - Calcium-dependent secretory vesicle-binding and lipid-binding proteins of Saccharomyces cerevisiae. AB - Yeast (Saccharomyces cerevisiae) cytosol was examined for the presence of calcium dependent membrane- or lipid-binding proteins that might play fundamental roles in membrane-associated phenomena in stimulated cells. A complex group of proteins was isolated from late log phase cultures of yeast strain YP3 on the basis of calcium-dependent association with yeast secretory vesicles isolated from the temperature-sensitive sec6-4 secretory mutant. The masses of the major proteins in this group were 32, 35, 47, 51, 55, 60 and 120 kDa. A similar group of proteins was isolated by calcium-dependent association with bovine brain lipids enriched in the predominant acidic phospholipids of the yeast secretory vesicles. The 47 kDa protein was highly purified when commercial yeast cake was used as the source of yeast cytosol. The 32 kDa and 60 kDa proteins were demonstrated to reassociate with lipids at calcium concentrations of 100 microM or higher, while no association was promoted by 2 mM-magnesium. The 47 kDa protein could be removed from lipids by reducing the calcium concentration to between 1 and 32 microM. The sequences of peptides isolated from digests of several of these proteins indicate that they are novel proteins but are insufficient to judge the possible homology of these proteins with mammalian membrane-binding proteins. The sequence data may be adequate to permit isolation and modification of the corresponding genes in order to assess the possible function of this class of proteins in stimulated cells. PMID- 1882549 TI - Killer system of Kluyveromyces lactis: the open reading frame 10 of the pGK12 plasmid encodes a putative DNA binding protein. AB - ORF 10 of the K2 plasmid from Kluyveromyces lactis encodes a small basic protein (22.3% lysine). The function of its product has been investigated. Western blot analysis, using an antibody against MS2 RNA polymerase/ORF 10 fusion protein, reveals a protein band with an apparent molecular weight of 14 kDa. The protein can bind a DNA-Sepharose column, and is eluted by 350 mM-salt. Immunoprecipitation experiments show that the ORF 10 protein coprecipitates with the linear genomic DNAs of the two killer plasmids (K1 and K2). From Western/Southern blot data, it is possible to conclude that the interaction between protein and DNA occurs directly, rather than via other protein(s). ORF 10 is easily detected by Western blot and its transcript is one of the most abundant of the K2 plasmid, suggesting that this protein may have a structural rather than a regulatory function. This possibility is also suggested by the observed sequence homology between the ORF 10 protein and the family of histone-like proteins. PMID- 1882550 TI - Applications of high efficiency lithium acetate transformation of intact yeast cells using single-stranded nucleic acids as carrier. AB - The highly efficient yeast lithium acetate transformation protocol of Schiestl and Gietz (1989) was tested for its applicability to some of the most important needs of current yeast molecular biology. The method allows efficient cloning of genes by direct transformation of gene libraries into yeast. When a random gene pool ligation reaction was transformed into yeast, the LEU2, HIS3, URA3, TRP1 and ARG4 genes were found among the primary transformants at a frequency of approximately 0.1%. The RAD4 gene, which is toxic to Escherichia coli, was also identified among the primary transformants of a ligation library at a frequency of 0.18%. Non-selective transformation using this transformation protocol was shown to increase the frequency of gene disruption three-fold. Co-transformation showed that 30-40% of the transformation-competent cells take up more than one DNA molecule which can be used to enrich for integration and deletion events 30- to 60-fold. Co-transformation was used in the construction of simultaneous double gene disruptions as well as disrupting both copies of one gene in a diploid which occurred at 2-5% the frequency of the single event. PMID- 1882551 TI - CDC15, an essential cell cycle gene in Saccharomyces cerevisiae, encodes a protein kinase domain. AB - The cell division cycle gene CDC15 is essential for the late nuclear division in the yeast Saccharomyces cerevisiae. The amino acid sequence of the 974 amino acids/110 kDa CDC15 gene product, as deduced from the nucleotide sequence, includes an aminoterminal protein kinase domain which contains a primary sequence mosaic showing patterns specific for protein serine/threonine kinases besides those for protein tyrosine kinases. Many protein kinases non-essential for growth are known. CDC15 represents an essential protein kinase like CDC7 and CDC28. A carboxyterminal deletion of 32 amino acids renders the protein inactive. PMID- 1882552 TI - Physical, transcriptional and genetical mapping of a 24 kb DNA fragment located between the PMA1 and ATE1 loci on chromosome VII from Saccharomyces cerevisiae. AB - A physical map of a contiguous DNA fragment of 60 kb, extending from the centromere to TRP5 on the left arm of the chromosome VII of Saccharomyces cerevisiae, strain IL125-2B, was established. Within a 31 kb region from PMA1 towards TRP5, a total of 12 transcription products ranging from 0.6 to 3.6 kb were identified in cells grown exponentially on rich medium. Near 87% of the DNA investigated was transcribed and on average one transcript, of 2.3 kb average length, was detected every 2.7 kb of DNA. The physical and genetical distances between the markers CEN7, pma1, leu1, pdr1 and trp5 were compared. A recombination frequency of 1 cM corresponds to an average distance of 3.3 kb between alleles in this region of chromosome VII. PMID- 1882553 TI - The DNA sequencing of the 17 kb HindIII fragment spanning the LEU1 and ATE1 loci on chromosome VII from Saccharomyces cerevisiae reveals the PDR6 gene, a new member of the genetic network controlling pleiotropic drug resistance. PMID- 1882554 TI - The YGL021 gene encodes a putative membrane protein with a putative leucine zipper motif. PMID- 1882556 TI - [Hybrid prosthesis implant-supported superstructures in edentulous jaw. 1. Case planning]. AB - Dental literature covers a wide range of implant-based denture supports. Based on static/dynamic as well as preventive periodontal considerations, rigidly anchoring the removable superconstruction of hybrid dentures using secondary splinting of four implants with telescope crowns or readymade cap-andpost systems, is generally appropriate in cases where the lower jaw is toothless. This makes possible an impeccable bridgeshaped design for the main part of the dentures, with wide-open inter-implant rincing areas. Clinical experience has shown that, in comparison to bridge dentures or rigid bridgework, secondary splinting in reconstructions greatly simplifies oral hygiene, particularly for elderly patients. PMID- 1882557 TI - [Gutta percha points--orientation aids in radiographic diagnosis]. PMID- 1882555 TI - The YGL022 gene encodes a putative transport protein. PMID- 1882558 TI - [Conservation concerns in multiband treatment]. AB - If (secondary) caries or amalgam fractures occur during fixed orthodontic treatment, the general dentist usually faces difficulties. Often temporary fillings are inadequate. Due to marginal leakage or break down they may jeopardize an orthodontic result. Step by step four cases of operative dentistry during fixed orthodontics are presented. A wait-and-see attitude or temporary measures for a longer period of time are definitely contraindicated. PMID- 1882559 TI - [Optimizing accuracy of Isosit IO composite restorations]. AB - Using a modified technique for producing composite inlays from Isosit IO resin material resulted in an optimized accuracy of inlays primary fit. SEM evaluation of MOD composite resin inlays manufactured by this technique and inserted on extracted teeth showed that the mean thickness of the luting composite space measured less than 50 microns. PMID- 1882560 TI - [Determination of working length in endodontics. 1. Radiographic method]. AB - Incomplete instrumentation and faulty obturation are the main reasons for endodontic failures. Exact determination of working length is one of the basic principles of a successful endodontic therapy. In this paper technique, benefits and problems of radiographic determination of endodontic working length are described. PMID- 1882561 TI - [Medications and Lyell syndrome]. AB - Lyell's syndrome, also known as toxic epidermal necrolysis, is one of the most devastating generalized skin disorders with a high mortality rate. The clinical manifestations are similar to those seen with extensive second-degree burns. Since drugs are considered to be responsible agents frequently, the dentist treating his patients with antibiotics and analgetics should be aware of this possibility. PMID- 1882563 TI - [Pouring titanium in dental laboratory. Development of a procedure]. PMID- 1882562 TI - [Titanium casting technique. Possibilities, problems, and hopes. Position report on pure titanium castings]. PMID- 1882564 TI - [Hybrid prosthetic implant supported suprastructures in edentulous mandible. Conus crowns and shell-pin-systems on HA-Ti-implants. 2. Prosthetic construction principles]. AB - Dental literature covers a wide range of implant-based denture supports. Based on static/dynamic as well as preventive periodontal considerations, rigidly anchoring the removable superconstruction of hybrid dentures using secondary splinting of four implants with telescope crowns or readymade cap-andpost systems, is generally appropriate in cases where the lower jaw is toothless. This makes possible an impeccable bridge-shaped design for the main part of the dentures, with wide-open inter-implant rincing areas. Clinical experience has shown that, in comparison to bridge dentures or rigid bridgework, secondary splinting in reconstructions greatly simplifies oral hygiene, particulary for elderly patients. PMID- 1882565 TI - [Temporomandibular joint diagnosis and therapy in complete denture wearers. Case demonstration of preprosthetic treatment]. AB - A physiological relation between discuss and condyle in the temporar-mandibular joint and an individual vertical dimension are important for TMJ-function without derangement. The loss of teeth and so the loss of vertical dimension safed by natural way result to a high percentage in disturbance of the masticatory system. The aim for patients with full dentures is to realize a physiological reference position in the TM-Joint and to reinstall their individual vertical dimension. The systematic treatment should be shown by a case report. PMID- 1882566 TI - [Determination of working length in endodontics. 2. Endometric determination of canal length]. AB - Electronic determination of endodontic working length has become very popular in the past few years. Nevertheles it has shown that the use of electronic apex locators cannot replace radiographic length determination, but can be a useful additional device in endodontics. Indication, benefits and limits of electronic length determination are described in this paper. PMID- 1882567 TI - [Study of traffic aptitude in relation to dental interventions]. AB - Applying a video game the traffic aptitude of patients was investigated before and after dental surgical treatment and local anesthesia. Local anesthesia or operative removal of impacted third molars does not reduce the psychophysical performance important for driving a car if there is no influence of other factors. The consequences of the obtained results are discussed even under forensic aspects. PMID- 1882568 TI - [Fracture resistance of human premolar with regard to morphological factors]. AB - 173 extracted human upper and lower premolars were tested for their fracture resistance with regard to the morphological factors proximal vertical fluting and occlusal abrasion. Upper and lower premolars revealed a comparable fracture strength. The proximal groove did not influence the fracture resistance. Markedly abraded teeth showed a higher fracture strength than premolars without or with only a moderate occlusal abrasion. But these differences were not significant statistically. In total the morphological factors, which were considered in this study, should not influence the fracture resistance. PMID- 1882569 TI - [Cutting and coagulating with high frequency currents: electrophysical effects of application of HF-surgery in dentistry]. AB - In HF-surgery the patient is part of the electric circuit. Often the surrounding of the patient and the dental surgeon himself are included in the electric circuit, especially if no neutral electrode is used. In the patients mouth metallic elements such as amalgam, gold crowns and other parts of metallic restorations influence the flow of the electric high frequency current, used for cutting and coagulating. Due to this very complex situation, sure and quick cutting without hazards for the patient is only possible, if the dentist understands the electro-physical principles of HF-surgery. PMID- 1882571 TI - [Recommendations for training with dental HF surgery apparatus]. AB - A training program for the application of dental electrosurgery is presented. Exercises on muscle tissue and pig jaws are suitable to get informations of the proper adjustment of the units as well as the treatment procedures. The necessity of proper handling is illustrated by the results of wrong manipulations. Better understanding of the facts during electrosurgery enables the dentist to avoid adverse effects in treating his patients. PMID- 1882570 TI - [Measurement of physical parameters in HF surgical techniques in dentistry]. AB - A method for measuring electrical parameters in dental electrosurgery and new data on this surgical technique are presented. A computer-controlled system which measures voltage, current, phase, power and impedance with high temporal resolution was applied to dentistry. Statistical analysis of many operations on freshly butchered pig jaws was performed. The impedance of oral soft tissues is higher during cutting, the power required smaller than stated in the literature. The influence of frequency, power-output control, anatomical structures, and metallic restorations on dental electrosurgery is discussed in detail. PMID- 1882572 TI - [Clinical applications of HF-surgery]. AB - The advantage of electrosurgery in minor dental surgery is demonstrated with regard to contraindications and especial precautions. In reports of case some indications are presented in combination with the treatment procedure. PMID- 1882573 TI - [HF surgery vs. laser surgery. Experimental study of use in periodontology]. AB - The purpose of this study was to evaluate the suitability of CO2 laser and two different electronically controlled electrosurgical units in periodontal surgery; both of the electrosurgical generators were recently designed for application in medicine. The study was performed on freshly butchered pig jaws. In addition to the management of the devices, the macroscopic and histologic effects of laser and high frequency energy on palatal gums, alveolar bone, tooth structures and filling materials were investigated. The handling of the electrosurgical units was efficient and smooth, the incisions showed accurate and reproducible results. In contrast to this the laser was uncomfortable to work with, additional safety arrangements were required and lesions in teeth and alveolar bone occurred easily. While the electronically controlled electrosurgical generators offer interesting aspects in some indications, CO2 laser seems to be unsuitable for periodontal surgery. PMID- 1882574 TI - [Medical apparatus legislation and dental HF surgery]. PMID- 1882575 TI - [Metals and alloys--corrosion, toxicology, sensitivity reactions 1]. AB - Alloys used in dentistry should not compromise the health of patients and of dental personal. All aspects of biocompatibility, such as corrosion, toxicity and allergic sensitization should be considered when base metal alloys or low gold alloys are used. In regard to health legislation, alloys should considered to be 'drugs'. Hazardous alloys should not be recommended, if the primary concern is cost. However, there is no or only little evidence to show, that either of the alloy systems used would rise health risks, exempting the beryllium containing alloys. They should not be used any longer. Probably, dental technicians are endangered by beryllium more than patients are. Some of the Ni-Cr-alloys were shown to corrode. There is less evidence of allergic senzitization caused by nickelcontaining dental alloys, than suspected first. PMID- 1882576 TI - [Chemical degradation of 15 composites--an SEM study]. AB - SEM-micrographs of 15 untreated composites that were laid in 96% ethanol were investigated. The surface of untreated samples show different fissures and cracks. Under the influence of alcohol the fissures become wider, the bond between fillers and unfilled resin enlarges, and the filling particles become prominent or fall out. Fine-grained hybrid composites with an unfilled resin densely compacted with microfillers, are least prone to degradation. PMID- 1882577 TI - [Study of properties of electrical root canal length measuring instruments]. AB - Six electrical instruments for locating the apex during endodontic treatment were tested in a laboratory investigation about currency, frequency and scale. Further we looked, whether all instruments show coincidence in the apex point. There are great differences in currency, frequency and scale (apex point). The reproducibility and the precision of an apex locator--at the time--depends an many factors and thus indication seems to be very limited. PMID- 1882578 TI - [Actual facial points as indication for bonded bridges]. AB - The results of recent long-term investigations show that the failure rates of adhesive bridges vary between 0% and 50%. Since only a few clinical and material effects--which in some cases are contradictory--on the success or failure could be definitively detected so far, establishment of the indication is of particular importance: Three-unit bridges have proved to have the best prognosis at present. There are no significant differences between the regions of the front and side teeth and between the upper and lower jaw. Abutments loosened to various degrees increase the risk as well as the parafunctional strain on abutments and the bridge. Caries and gingivitis is rarely observed in patients with adhesive bridges. This is due to the follow-up care practised in the studies and by no means obviates the need for regular checks of hygiene. PMID- 1882579 TI - [Survival rate analysis and clinical follow-up of tooth-colored restorations of CEREC]. AB - A survival rate analysis of 426 CEREC restorations, made in a general dentistry practice, was carried out for a period of 3 years. 12 restorations were lost. Thus the Kaplan-Meier probability of survival decreased to 0.95 within 23 months. The mortality rates of restorations in molars and of restorations in premolars showed no significant difference. The patients assessed the treatment results in 96% of the cases as "good" or very good". In 4 cases chewing sensibility necessitated the reconstruction of the inlay restoration. With increasing observation time a reduced quality of the marginal integrity was found. PMID- 1882580 TI - [Gardner syndrome--an interdisciplinary disease picture]. AB - Gardner's syndrome, completely expressed, consists of a triad of symptoms: polyposis of the colon, osteomatosis and mesenchymal tumours of the skin. Inheritence is autosomal dominant. In a follow-up examination amongst eleven patients with polyposis intestinalis a typical constellation of symptoms of Gardner's syndrome was found in eight. With increasing age of the patients polyposis of the colon shows a marked tendency to malignant degeneration. Because osseous lesions and striking skin pigmentation in the facial and jaw region precede polyposis coli, dentists may have an important role to play in the early detection of Gardner's syndrom. The disease is illustrated by a case report. PMID- 1882581 TI - [Optimization of inlay care: pin anchorage]. AB - The pin-technique in the application of inlays offers two important advantages: once the possibility to prepare with the utmost preservation of dental substance and highest stability and then to have more indications for inlays. Compared to the general technique in using inlays there are two major difficulties: keeping the parallelism of several pins and the danger of hurting the pulp. After a certain period of training both can be managed. PMID- 1882582 TI - [Dorsal border of denture base after SR-Ivocap polymerization]. AB - The amount of dorsal borderspace of upper-plates after polymerisating in different dental laboratories has been measured and compared by statistically methods. This result showed a conspicuously small deviation. The overall average was to be found in the range of only 227 microns +/- 10.5 microns after water laging for 4 weeks. This amount is conformable to the results of Marx. There is no interpretation of the high values measured by Peroz recently. This present results confirm on the contrary the clinically verification of the SR-Ivocap polymerisating equipment. PMID- 1882583 TI - [Hydroxyapatites in periodontopathies]. AB - In 58 cases, 611 teeth with an advanced periodontal disease are been treated with the usual procedure like hygiene motivation and scaling. After this initial phase, open root scaling and defect augmentation achieved in nearly all cases improved clinical results. PMID- 1882584 TI - [Study of cell supportability of clinically used soft denture liners]. AB - The application of six soft denture liners showed different effects on the growth of gingival fibroblasts. The morphological and autoradiographical analyses revealed a graduated cellular biocompatibility. The results provide information for further examinations in more detail concerning the clinical biocompatibility of these materials. PMID- 1882585 TI - [Clinical study of electrical root canal length instruments]. AB - In a clinical study on 100 root canals we measured the difference between the length, which can be received by a roentgenogramme, and the length, which can be received by an electrical device. In cases with vital exstirpation in 80% we got a good conincidence, but in cases of pulp gangraena there were great differences. Indication of electrical devices for measuring tooth length only can be seen together with an existing X-ray; it is very important, whether the canal is dry enough for exact measuring. PMID- 1882586 TI - [Metals and alloys--corrosion, toxicology, and sensitivity reactions 2]. PMID- 1882587 TI - [IPS-Empress: a new ceramic technology]. PMID- 1882588 TI - [Sexual dimorphism in the brain and drug actions: with special reference to the sex difference in the functional effects of maternal exposure to drugs in the littermate offspring]. AB - It has long been known that in mammals there is a sex difference in the drug metabolizing enzyme activity that is reflected in the sex-related difference in the action of barbiturates and some other drugs. Recently, sex differences in the structure and function of the brain in humans and other primates have been demonstrated by many investigators. This review focused on the sex difference in the brain mainly of the rat studied with physiological, biochemical or even molecular endpoints. Our experimental results on the modulating effects of sex steroids for dopaminergic neurons were included. In addition, the findings that maternal exposure to various CNS acting drugs resulted in a marked sex difference in the brain function of the offspring when assessed with a number of measures such as open-field behavior, tolerance to the exposed drug itself, thermic responses to chlorpromazine, and the pituitary response to releasing hormones were presented and discussed. PMID- 1882589 TI - Some aspects of negative symptoms of the residual schizophrenia. PMID- 1882591 TI - Integrative approaches to the treatment of the schizophrenic disorders. PMID- 1882590 TI - Positron emission tomography study of phencyclidine users as a possible drug model of schizophrenia. PMID- 1882592 TI - Frontal dysfunction of chronic schizophrenia--the pros and cons in neuropsychological assessment. PMID- 1882593 TI - Neurophysiological study of schizophrenia: an abnormality of P3s. PMID- 1882594 TI - The new challenges in psychopathology. PMID- 1882595 TI - Antimicrobial activities on Mediterranean plants. AB - Antimicrobial activities were tested for 22 plant species collected in the Valencian Community, using 9 different fungal and 6 bacterial strains which contaminate food and crops. Some of them showed fungizidal and bactericidal activity against some of the microorganisms tested. PMID- 1882597 TI - Physico-chemical and bacteriological parameters in a hypereutrophic lagoon (Albufera Lake, Valencia, Spain). AB - Several physico-chemical parameters related to water quality, as well as saprophytic and public health-related heterotrophic bacterial groups were studied in a hypereutrophic lake (Albufera, Valencia) at different seasons. Total microscopic and viable counts were compared, and, together with faecal indicators, were determined in water samples from different sites. Heterotrophic bacteria grown on nonselective medium were identified to genus level and a diversity index was calculated. Pseudomonas-Alcaligenes was the most frequently isolated group from all sampling sites along the study, following by Moraxella, Acinetobacter, Vibrio and Aeromonas. The relationships between all parameters were searched by Principal Components Analysis (PCA). PMID- 1882596 TI - Saprophytic and keratinolytic fungi associated with animals hair from Riyadh, Saudi Arabia. AB - Hair samples from different animals collected from different sites in Riyadh, Saudi Arabia were examined for the presence of saprophytic and keratinolytic fungi. Fifty-one specimens were examined of which 19 were from rabbits, 13 from sheeps, 12 from camels and 7 from horses. Forty-eight species and one variety which belong to 24 genera were collected during this investigation. The most common genera were Aspergillus and Chrysosporium. In low frequency, members of the genera Thermoascus, Scopulariopsis, Alternaria, Penicillium, Rhizopus, Botryotrichum, Fusarium, Ulocladium and keratinophilic fungi of the genera Microsporum, Trichophyton and Arthroderma were also recovered. PMID- 1882598 TI - [Shigella endotoxin protein--its isolation and physicochemical characteristics]. AB - The scheme of the isolation of endotoxic protein from S. sonnei 9090 is presented. The isolation procedure includes the 10-minute hot (at 68 degrees C) extraction of protein from endotoxin with 45% aqueous phenol, the precipitation of protein from phenolic extract with 9.5 volumes of 95% ethanol, the purification of protein from lipid material and pigments by multiple extraction with the mixture of chloroform and ethanol in the proportion 2:1 by volume. The yield of protein obtained with the use of this isolation scheme is about 3% of the initial endotoxin preparation. Protein preparations obtained in accordance with this scheme contain 92-95% of protein (determined by Lowry's method), 2.3 3.0% of saccharides (determined by the phenol-sulfate method) and 0.02% of hexose amine, its presence indicating that the preparations contain lipid A (or its fragments) which is firmly bound with endotoxic protein and cannot be extracted with chloroform. As shown in the passive hemagglutination inhibition test, the content of endotoxin in the preparations is less than 0.003%. Out of 7-11 bands revealed by electrophoresis in 15% polyacrylamide gel in the presence of sodium dodecyl sulfate, 3 main bands have molecular weights of 43, 38 and 18 KD. Three antigens differing in their electrophoretic mobility and diffusion rate in 1% agarose gel can be detected in the preparations by the method of immunoelectrophoresis with the use of antisera to both endotoxin and endotoxic protein. PMID- 1882600 TI - [The use of the indirect hemagglutination reaction for the serodiagnosis of HIV infection]. AB - An assay system, based on the passive hemagglutination test and permitting the serodiagnosis of HIV infection with correct results in more than 99% of cases, has been developed. Three kinds of freeze-dried erythrocyte diagnostica (with shelf life exceeding 6 months), possessing high serological activity and sensitized with recombinant gene-engineering polypeptides, have been obtained. The proposed assay system is highly promising for mass examination of sera for the presence of antibodies to HIV due to the simplicity of assay techniques, the possibility of storing the diagnostica within a wide range of temperatures (4 degrees-30 degrees C) and obtaining results in a short time (3 hours). PMID- 1882602 TI - [An electron microscopic study of the intercellular contact of a vaccinal strain of Francisella tularensis with gram-negative and gram-positive bacteria]. AB - The use of transmission electron microscopy (the negative contrast and ultrathin section techniques) has made it possible to show that F. tularensis vaccine strain is capable, under normal conditions and in mixtures with other gram negative and gram-positive bacteria, of forming cell aggregations with close contacts between cells, this contact being probably irreversible. The ultrastructure of bacteria taking part in the formation of intercellular contacts remains intact. PMID- 1882601 TI - [A method for assessing the microfloral status of the human intestines by the quantity of adhesion-active bacteria and by the type of adhesins]. AB - The method for the evaluation of the state of intestinal microflora in the diagnosis of enteric diseases by the determination of the number of actively adhesive bacteria and the type of adhesins in the primary culture of human microflora has been developed. This method permits the simultaneous analysis of all colonies grown in a given Petri dish by the sign of their adhesion, which eliminates the possibility of mistakes due to the occasional choice of colonies, as it may happen in the agglutination test. The time necessary for the study of adhesive properties is reduced, as the result is evaluated as early as on day 2 after the inoculation of the seed material. It is also of importance that the method is simple in realization, needs no special equipment, preparation and staining of the material. To determine the type of adhesins, a series of identical inoculations may be obtained by replication with the use of red blood cells of different animals. The proposed method may be used for the confirmation of the etiological role of enterobacteria as evidenced by the presence of high percentage of their actively adhesive colonies. PMID- 1882599 TI - [Shigella endotoxin protein--its electrophoretic and serological properties]. AB - The electrophoretic analysis of lipid A-associated protein (LAP), obtained from S. sonnei, in polyacrylamide gel in the presence of sodium dodecyl sulfate and urea has revealed the heterogeneity of the preparation; it has found to contain three main components with molecular weights of 43, 38 and 18 KD and some minor components with molecular weights of 49, 45 35, 30, 29, 27, 5, 21 and 14 KD. The electrophoretic mobility of the main protein components in the isolated preparation of LAP coincides with that of endotoxin components. The dissociation of proteins and lipopolysaccharide in the process of boiling the endotoxin in 2% sodium dodecyl sulfate is indicative of the noncovalent binding of these components. LAP contained in the endotoxin, in contrast to isolated LAP, is resistant to trypsin and proteinase K. The enzyme immunoassay (EIA) system with the use of LAP as a component of its solid phase has been developed, which makes it possible to carry out the quantitative determination of antibodies to this protein. The EIA system shows high sensitivity in the determination of anti-LAP IgG antibodies: in hyperimmune rabbit sera their titer is 1:250,000-1:800,000. As shown by the method of competitive EIA, the antigenic affinity of LAP of different origin corresponds to the degree of taxonomic propinquity of microorganisms: the maximal degree of cross reactions is observed between LAP obtained from S. sonnei, S. flexneri and Escherichia coli, while their affinity to Salmonella typhi is considerably less; remote microbial species (Bacterium bifidum and Sarcina marcescens) give practically no cross reactions. PMID- 1882603 TI - [An oral chemical vaccine from the hypertoxigenic strains of the causative agent of cholera KM-76 Inaba and KM-68 Ogawa]. AB - The material on the development of chemical vaccine, prepared from two newly formed strains (KM-76 Inaba and KM-68 Ogawa) and intended for oral administration, is presented. The conditions for the submerged cultivation of these strains have been established, which makes it possible to increase the production of choleragen 8- to 10-fold and O-antigen 3- to 4-fold in comparison with V. cholerae natural strain 569B. The maximum accumulation of neuraminidase, protease, phospholipase, along with choleragen, has been registered in the logarithmic phase and that of O-antigen, in the stationary phase of growth. The use of strains KM-76 and KM-68 has led to the fourfold increase of the specific activity of the main immunogens, thus permitting the respective increase of the yield of the oral vaccine without changes in its high capacity for the formation of specific antibodies and its low residual toxigenicity. PMID- 1882604 TI - [The action on the immune system of respivax--a polybacterial vaccine for the peroral immunotherapy and immunoprophylaxis of nonspecific respiratory tract infections]. PMID- 1882605 TI - [The specific activity of a multicomponent vaccine made from the antigens of opportunistic microorganisms]. AB - Multicomponent vaccine prepared from the antigens of 4 representatives of opportunistic microflora possesses high specific activity. The passive hemagglutination (PHA) test with the use of associated diagnosticum showed that antibody titers in the sera of immunized rabbits increased 10- to 10(4)-fold in comparison with the titers observed prior to immunization. The PHA test with the use of the antigens contained in the vaccine revealed the accumulation of antibodies to each of the 4 components of the preparation in the blood sera of immunized rabbits. When stored at 4 degrees C, the vaccine was shown to retain its specific activity for 5 years (the term of observation). PMID- 1882606 TI - [The chromosome-damaging action of 2 chemical vaccine contaminants on mice]. AB - The cytogenetic effects of two chemical agents, hydroxylamine used for the destruction of bacterial cells and thimerosal added to many immunobiological preparations as preservative, were studied in vivo by their action on the marrow cells of C57BL/6J mice. The preparations under study, when injected intraperitoneally in a wide range of doses, including subtoxic ones, induced no chromosomal aberrations. At the same time cyclophosphamide, an antitumor cytostatic agent used for positive control, produced a pronounced damaging effect on chromosomes. PMID- 1882607 TI - [The action of ribosomal preparations on nonspecific resistance to bacterial infection and on early tolerance to endotoxic shock]. AB - Ribosomal preparations from Shigella flexneri and Shigella sonnei, introduced parenterally into mice, enhance their resistance to infection with the causative agents of typhoid fever and staphylococci. This effect is considerably less pronounced than that produced by the preparation of homologous lipopolysaccharide isolated by Boivin's method. After the administration of ribosomes nonspecific resistance to bacterial infective agents lasts for a short time. Ribosomal preparations do not enhance the resistance of mice to the lethal action of endotoxin. PMID- 1882608 TI - [The efficacy of Klebsiella pneumoniae bacteriophage in the therapy of experimental Klebsiella infection]. AB - The effectiveness of specific phage therapy was studied on Klebsiella experimental sepsis in noninbred white mice, caused by the intraperitoneal injection of K. pneumoniae highly virulent strain K2 5055 into the animals. For treatment, Klebsiella polyvalent bacteriophage administered on day 2 after the infection of the animals with Klebsiella was used. The study revealed that bacteriophage could be detected in the blood and internal organs of the animals within 24 hours irrespective of the route of its administration: intraperitoneal, intravenous or intranasal. The bacteriophage preparation, introduced intraperitoneally, was shown to be effective in the treatment of generalized Klebsiella infection. One daily intraperitoneal injection of Klebsiella bacteriophage for 15-20 days proved to be the optimum scheme of treatment. In contrast to chemotherapeutic preparations, bacteriophages had no effect on normal microflora and did not aggravate dysbiotic disturbances. For this reason, bacteriophages may become one of alternative antimicrobial remedies, selectively affecting infective agents. PMID- 1882609 TI - [The protective action of interferon type I in experimental Salmonella infection]. AB - The effect of interferon, type 1, on the course of Salmonella infection in mice has been studied. The study has shown that the injection of homologous interferon of type 1 leads to the rapid elimination of the infective agent from the blood and organs of infected mice. Morphological study has shown that the injection of the preparations of interferon of type 1 may diminish pathological changes in the organs of the infected animals and the coagulation system of their blood. PMID- 1882610 TI - [Immunoglobulin efficacy for intravenous administration in the therapy of newborn infants with a suppurative infection]. AB - The data on the results of clinico-immunological examination of 46 infants having purulent inflammatory infections in the first month of their life and treated with (a) immunoglobulin for intravenous injection, (b) with hyperimmune antistaphylococcal plasma and immunoglobulin for intravenous injection and (c) without the use of specific hyperimmune preparations are presented. The clinico laboratory data thus obtained (the levels of serum immunoglobulins and the content of T-rosette-forming lymphocytes) are indicative of the expediency of including the intravenous injection of donor immunoglobulin into the complex therapy of newborn infants with severe and moderate forms of purulent inflammatory infections at an early period of the disease irrespective of its etiology. PMID- 1882611 TI - [The immunocorrective properties of bacterial preparations (lactobacterin, bifidumbacterin) and bemitil in pregnant women with a urogenital infection]. AB - The results of the analysis of the cell-mediated and humoral factors of the peripheral blood and cervical mucus in pregnant women with urogenital infections (pyelonephritis, colpitis, cervicitis, endocervicitis) and in healthy pregnant women are presented. These results indicate that considerable changes in the systemic immunity of the body and in the local antiinfectious protection of the reproductive tract develop in pregnant women with urogenital infections. The prescription of bifidumbacterin and lactobacterin to the patients during pregnancy (intravaginally) and bemitil after parturition (orally) completely restores the functional validity of their immune system and decreases the number of postnatal complications. PMID- 1882612 TI - [The dependence of the functional activity of "immune" macrophages on T-cells]. AB - The dependence of the functional activity of the peritoneal macrophages of mice immunized with Francisella tularensis vaccine strain on the presence of T-cells in the culture has been studied. The elimination of "immune" macrophages and sensitized T-lymphocytes by means of anti-Thy-1-2-serum has been shown to lead to a sharp decrease in both ingestive and digestive functions of the phagocytic mononuclears of peritoneal exudate to the level of the activity of macrophages isolated from intact animals. PMID- 1882613 TI - [The formation of delayed hypersensitivity to mycobacterial antigens]. AB - In experiments on guinea pigs and BALB/c mice delayed hypersensitivity to mycobacterial antigens was induced by the sensitization of the animals with live BCG or killed Mycobacterium bovis or M. avium in incomplete Freund's adjuvant. In the study of the dynamics of the development of skin reactivity to tuberculin some advantages of the sensitization of guinea pigs with live mycobacteria were revealed, while after the revaccination of the animals no development of secondary cell-mediated immune response was observed. The immunization of guinea pigs with atypical mycobacteria prior to their sensitization with BCG was found to lead to the development of higher skin reactivity to allergen prepared from atypical mycobacteria than skin reactivity to tuberculin. PMID- 1882614 TI - [Successes and the outlook in the study of pathogenic microorganisms in vivo in the implanted chamber model]. PMID- 1882615 TI - [The possible mechanism of the formation of antitoxic immunity to tetanus as a result of a blood transfusion]. PMID- 1882616 TI - [P. F. Zdrodovskii (on the centenary of his birth)]. PMID- 1882617 TI - [The biochemical and immunological properties of group A type M 29 streptococci cultured in the presence of a bovine blood serum preparation]. AB - The influence of the preparation of cattle blood serum on group A streptococcus, type M 29, has been studied. The study has revealed that the addition of 17% of dialysis water obtained from a fraction of cattle blood serum to the standard culture medium (3% Todd-Hewitt broth) produces changes in the amino acid composition of the cell walls of M+ variant without altering the antiphagocytic resistance of the mutant thus obtained. The dialysate of the pepsin digest of the cell walls of the mutant contains Fc-receptors and receptors to fibrinogen, while the initial strain contains only receptors to fibrinogen which are, in this case, the pepsin fragments of M protein. The study has revealed similarity in the amino acid compositions of these proteins (receptors to fibrinogens) of phenotypes M+ and M2+. Thus, our data confirm that the initial strain and the mutant belong to different phenotypes of group A streptococcus, type M 29. PMID- 1882618 TI - [The experimental and clinical effect of ciprofloxacin on the microflora of the gastrointestinal tract]. AB - The study of the influence of cyprofloxacin on the microflora of the gastrointestinal tract has been made under experimental and clinical conditions. As revealed in this study, cyprofloxacin produces a corrective effect on the intestinal microflora; the action of this preparation, in contrast to that of other antimicrobial preparations, is retained for a long time. In patients having duodenal ulcer with bacteriosis caused by Campylobacter pylori and with intestinal dysbacteriosis the combination of cyprofloxacin and cimetidine yields a higher therapeutic effect than the use of cimetidine alone. PMID- 1882619 TI - [A comparison of their virulence for mice and the enzymatic activity of Streptococcus pneumoniae strains]. AB - In most cases no correlation between the virulence of S. pneumoniae and their enzymatic activity was registered in 101 S. pneumoniae strains isolated in pneumococcal infections of different localization. Pneumococcal strains belonging to different serotypes and characterized by their low virulence for mice (LD50 = 10(6) colony-forming units) had the highest neuraminidase and protease-alzolase activity in comparison with highly virulent cultures of these bacteria. In pneumococcal cultures in the R-form avirulence for mice occurred mainly in combination with low enzymatic activity. PMID- 1882621 TI - [The autologous intestinal microflora in the postresuscitation period after acute blood loss in rats]. AB - In this work the data obtained in the study of intestinal microbiocenosis in rats on the third day of the postresuscitation period after acute blood loss are presented. The quantitative and qualitative shifts of microflora at different biotopes, such as the wall of the small intestine, the parietal microflora of Peyer's patches, the contents and wall of the large intestine, have been characterized. Some specific features of dysbiotic changes have been revealed in comparison with the shifts of intestinal microflora in cases of dysbacteriosis caused by other reasons. The translocation of different microorganisms, including Bacterium bifidum and lactobacilli, into mesenteric lymph nodes, the liver, the spleen and the blood has been observed. PMID- 1882620 TI - [The capacity of microorganisms in the genus Campylobacter for mobile growth]. AB - The capacity of Campylobacter for mobile was studied on the cultures of 5 reference strains and 153 newly isolated strains of clinical origin, used as an experimental model. The study revealed that the capacity of Campylobacter for mobile growth was best manifested in cases of its cultivation in nutrient media based on tryptose agar with the density of 0.35% at 37 degrees C in the usual atmosphere: under these conditions the capacity for mobile growth was exhibited by 92.8% of all cultures of the strains under study. The description of the cultural properties of Campylobacter cultures exhibiting mobile growth demonstrated the difference between the phenomenon of mobile growth and the phenomenon of clustering. The possibility of using the capacity of Campylobacter for mobile growth for the rational diagnosis of Campylobacter infection was suggested. PMID- 1882622 TI - [The prospects for using immunoadsorption in AIDS therapy]. PMID- 1882623 TI - [The possibility of long-term prognosis in influenza A pandemics]. AB - On the basis of the analysis of the most significant influenza A pandemics over the period of 300 years, compared with periodic long-term changes in the climate and the cycles of solar activity, regularities in the manifestation of the biorhythms of the epidemic activity of influenza A virus have been established. The prognosis of pandemics for near and remote future is proposed. PMID- 1882624 TI - [The results of using direct solid-phase immunoenzyme analysis for assessing the specific activity of rabies vaccines]. AB - The effectiveness of the solid-phase enzyme immunoassay (EIA) in the determination of the specific activity of rabies vaccines is evaluated in comparison with that of the protective test in mice. Inactivated tissue-culture, concentrated tissue-culture and purified cerebral tissue vaccines for human use were studied. The methods for performing two EIA variants and evaluating the results are described. The average level of correlation between the results of EIA and the protective test for vaccines of different groups was revealed (0.546), the highest correlation index being obtained for tissue-culture vaccines: 0.753. On the basis of the data obtained in this study the expediency of using EIA for the determination of the specific activity of rabies vaccines has been substantiated. PMID- 1882625 TI - [The immunodiagnosis of tick-borne encephalitis by using the indirect immune rosette formation reaction]. AB - 200 patients suspected for tick-borne encephalitis (TBE) were examined by the method of the indirect immune rosette-formation test. In 70.15% of patients with the serologically confirmed diagnosis of TBE immune lymphocytes were detected as early as on day 1 of examination. The level of rosette formation was higher in the meningeal form of the disease. Rosette-forming lymphocytes were also detected in 24.06% of patients with the serologically unconfirmed diagnosis of TBE. The test is proposed for the early diagnosis of TBE. PMID- 1882626 TI - [A comparative study of the sensitivity and specific activity of an immunoenzyme test system for determining class-M antibodies to the hepatitis A virus]. AB - The diagnostic value of the first experimental production batches of assay kit "DIAGN-A-HEP", produced at the Institute of Poliomyelitis and Viral Encephalitides (USSR Acad. Med. Sci.) and intended for the determination of IgM to hepatitis A virus (HAV) in the enzyme immunoassay (EIA), has been studied in comparison with that of the internationally known and widely approved commercial EIA system "HAVAB-MEIA" for the determination of antibodies to HAV (the product of Abbott, USA). The study has revealed that the EIA kit "DIAGN-A-HEP" is highly sensitive and specific, and the diagnostic value of this kit is not inferior to that of the commercial assay system "HAVAB-MEIA". On the basis of this study the use of the EIA kits "DIAGN-A-HEP" in medical practice has been allowed by the decree of the Ministry of Health of the USSR. PMID- 1882627 TI - [The use of the method of the complete advisability function for evaluating the quality and standardization of the plates in solid-phase EIA]. AB - An attempt to use the method of the complete advisability function for the evaluation of the quality of plates and their standardization in the enzyme linked immunosorbent assay (ELISA) has been made. Correlations have been empirically established, thus making it possible to calculate the optimum proportions of different ELISA factors: the dose of the antigen (antibody) and the time of sorption, which ensures the best ELISA results with a given type of plates. PMID- 1882628 TI - [A strategy for controlling measles at the current stage]. PMID- 1882629 TI - [The side effects of vaccines used in prophylactic inoculation schedules]. PMID- 1882630 TI - [The status of and outlook for the development of a raw materials base for the manufacture of culture media]. PMID- 1882631 TI - [Marburg hemorrhagic fever]. PMID- 1882632 TI - [The microevolution of anthropophilic prokaryotes as a factor altering the activity of epidemic processes. The microevolution of pathogenicity]. PMID- 1882633 TI - [An organizational model for the activities of microbiology laboratories]. PMID- 1882634 TI - [Cyclic nucleotides, prostaglandins and thrombocyte aggregation in rats poisoned with "murine" Yersinia pestis toxin]. AB - Y. pestis "mouse" toxin, introduced intraperitoneally into rats in a dose of LD100 [correction of LG100], produces phasic changes in the thrombin-induced aggregation of thrombocytes and the content of prostaglandins and cyclic nucleotides in them. As the result of the damaging action on the endothelium of blood vessels at the initial period of intoxication, the concentration of prostaglandin 6-keto F1 alpha in blood plasma and cAMP [correction of cAMR] in thrombocytes sharply decreases, which causes the enhancement of thrombin-induced cell aggregation. At a later period the level of prostaglandin E in the cells sharply rises. At later irreversible stages of shock, induced in the cells of Y. pestis "mouse" toxin, the content of cGMP in cells sharply increases, which leads to the development of the phase of thrombocyte hypoaggregation. PMID- 1882635 TI - Stabilisation of neurone number in the inferior olivary complex of aged 'Purkinje cell degeneration' mutant mice. AB - Virtually all cerebellar Purkinje cells degenerate in 'Purkinje cell degeneration' (pcd) mutant mice between postnatal day (P) 17 and P45. The inferior olivary complex (IOC) in these mutants undergoes atrophy subsequent to the deprivation of its major cortical target; the number of IOC neurones declines by 18% by P23 and by 49% by P300. In the present study we used control (+/?) and mutant (pcd/pcd) mice that were 14-15 months old to determine whether any further cell loss is observed in the pcd IOC after P300. Nerve cell counts were obtained from serial paraffin sections of the medulla oblongata. The corrected estimate of neurone number in the left IOC of control mice was 12,785 +/- 794 cells (mean +/- SD, n = 5); in pcd mutants that number was 6,722 +/- 535 (n = 5). The 47% difference between control and mutant mice was highly significant (p less than 0.001). The perikarya of surviving IOC neurones were atrophic. Compared to P17 mutants, pcd homozygotes manifest a 50% cell loss by P428-P446, which does not practically differ from the deficit found on P300. These results suggest that, once a critical neuronal mass degenerates in the IOC of pcd mutants, the remaining neurones become stabilised and no further loss is observed even at an advanced age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882636 TI - Extracellular neurofibrillary tangles associated with degenerating neurites and neuropil threads in Alzheimer-type dementia. AB - We examined the cellular components of extracellular neurofibrillary tangles (E NFT) in the hippocampal areas in cases with Alzheimer-type dementia. Immunohistochemically, the E-NFT were labeled for the C terminus of tau and glial fibrillary acidic protein. Moreover, the majority of the E-NFT was associated with intensely argyrophilic rods and with tau- and ubiquitin-immunoreactive dots. Ultrastructurally, the E-NFT consisted mainly of extracellular paired helical filaments (PHF) and astroglial processes. The extracellular PHF tended to be straighter and thinner. One third of the E-NFT was associated with small degenerating neurites containing many dense bodies and with neuropil threads containing PHF. These findings suggested that extracellular PHF promote both intense astroglial reaction and neuritic alteration, and that the E-NFT are continuously changing their morphology. PMID- 1882637 TI - Light and electron microscopic and immunohistochemical observations of the Onuf's nucleus of amyotrophic lateral sclerosis. AB - We examined the Onufrowicz nucleus (Onuf's nucleus) of ten sporadic amyotrophic lateral sclerosis (ALS) patients with light and electron microscopic and immunohistochemical methods. Neurons in the Onuf's nucleus of ALS patients were better preserved than those in anterior horn cells. However, some showed morphological changes in the nucleus, namely, central chromatolytic changes, Bunina bodies, ubiquitin-positive filaments and spheroids. The Onuf's neurons of ALS patients showed more argentophilia than those of non-ALS patients. Electron microscopic observations revealed that neurofilaments were relatively more numerous in the Onuf's neurons of ALS patients. Bunina bodies and degenerated neurites were also seen in the Onuf's nucleus. In conclusion, the Onuf's nucleus in sporadic ALS patients showed some morphological changes similar to those noted in anterior horn cells. PMID- 1882638 TI - Interrelationships between increased vascular permeability and acute neuronal damage following temperature-controlled brain ischemia in rats. AB - This study examined regional patterns of increased vascular permeability and morphological indicators of acute neuronal injury following normothermic and mildly hyperthermic forebrain ischemia. Rats underwent 20 min of four-vessel occlusion during which intraischemic brain temperature was maintained at either 37 degrees C or 39 degrees C. At 45-min recirculation, the blood-brain barrier (BBB)-tracer horseradish peroxidase was injected and rats were perfusion-fixed at 1-h recirculation for light and electron microscopic analysis. In normothermic and hyperthermic rats, sites of increased vascular permeability were spatially correlated with dark shrunken type IV neurons. Neuronal alterations within cortical, hippocampal, striatal, and thalamic areas ranged from mild cytoplasmic vacuolation and mitochondrial swelling to severe cytoplasmic shrinkage and increased density. Although dark shrunken neurons were routinely associated with permeable blood vessels in both temperature groups, dark neurons were not detected in regions demonstrating an intact BBB. Following normothermic brain ischemia, the appearance of dark shrunken neurons was restricted to the cerebral cortex and striatum. In both temperature groups, luminal leukocytes were detected within otherwise well-perfused forebrain microvascular beds. Our studies suggest a close interrelationship between postischemic microvascular abnormalities, including increased vascular permeability, and morphological indicators of acute neuronal injury following brain ischemia. PMID- 1882639 TI - Neuromyopathy and restrictive cardiomyopathy with accumulation of intermediate filaments: a clinical, morphological and biochemical study. AB - The clinical, morphological and biochemical findings of a sporadic case, showing accumulation of desmin-type intermediate filaments in skeletal muscle and myocardium are described. Desmin storage was demonstrated by immunofluorescence, sodium dodecyl sulfate gel electrophoresis and two-dimensional gel electrophoresis. These findings are in agreement with those of Rappaport et al. (FEBS lett. 231:421-425, 1989). A sensory-motor polyneuropathy was established by electrophysiological studies and, ultrastructurally, intramuscular nerves showed accumulation of neurofilaments and neurotubules with formation of axonal spheroids. These findings are discussed considering all previous reports with related conditions. PMID- 1882640 TI - Immunohistochemical study on the distribution of alpha and beta subunits of S-100 protein in brain tumors. AB - The immunohistochemical distribution of alpha and beta subunits of S-100 protein (S-100 alpha, S-100 beta, respectively) in 138 cases of human brain tumors was investigated by the avidin-biotin immunoperoxidase method. Brain tumors can be divided into four groups: group 1 [S-100 alpha (+) and/or S-100 beta (+)]; astrocytoma, glioblastoma, ependymoma, subependymoma, oligodendroglioma, choroid plexus papilloma, gangliocytoma, meningioma, chordoma, malignant melanoma. Group 2 [S-100 alpha (+) and S-100 beta (-)]; pineoblastoma, pituitary adenoma, craniopharyngioma, rhabdomyosarcoma. Group 3 [S-100 alpha (-) and S-100 beta (+)]; acoustic Schwannoma. Group 4 [S-100 alpha (-) and S-100 beta (-)]; medulloblastoma malignant lymphoma, germinoma. The S-100 beta immunoreactivity pattern in brain tumors was similar to those obtained using conventional anti-S 100 protein sera. In the first group of brain tumors both the number of positively stained tumor cells and the staining intensity were generally greater for S-100 beta than for S-100 alpha with a few exceptions including one gemistocytic astrocytoma, one subependymoma, one malignant melanoma, and some cases of glioblastomas. As to the relationship between malignancy and S-100 protein in glioma, S-100 beta immunoreactivity decreased according to degree of malignancy, while that of S-100 alpha varied, suggesting a heterogeneity of tumor cells in glioblastomas. Immunostaining for S-100 alpha and S-100 beta might become a useful diagnostic procedure in brain tumors and may give us more detailed and precise data of S-100 protein in brain tumors. PMID- 1882641 TI - Intracellular calcium levels in canine basilar artery smooth muscle following experimental subarachnoid hemorrhage: an electron microscopic cytochemical study. AB - Changes in intracellular calcium levels in canine basilar arterial smooth muscle were semiquantitatively measured by an electron microscopic cytochemical technique using a combined oxalate-pyroantimonate method. Measurements made after subarachnoid hemorrhage were compared with those made after contraction induced by prostaglandin F2 alpha. Fifteen minutes after topical application of the drug, when the basilar artery was constricted by 20%, 15% of smooth muscle cells contained a large amount of intracellular calcium. One hour later, the diameter of the basilar artery and intracellular calcium precipitation returned almost to control levels. Fifteen minutes after the first intracisternal injection of autologous blood, when acute vasospasm was angiographically evident, 13% of smooth muscle cells contained a large amount of calcium. After 1 h, when acute vasospasm had already abated, the number of smooth muscle cells containing a large amount of calcium markedly increased to 37% and some smooth muscle cells showed early degenerative findings such as intracytoplasmic vacuoles including calcium accumulation. After 48 h, when delayed vasospasm had already started, the calcium deposits and early degenerative changes had decreased significantly. After 49 h and 4 days (1 h and 48 h after the second injection of blood), the change in the amount of calcium was the same as at 1 h and 48 h after the first injection, respectively, but degeneration of smooth muscle cells increased. Therefore, acute vasospasm after subarachnoid hemorrhage may be caused by an initial elevation of intracellular calcium levels, as is the case with drug induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882642 TI - Effect of human T lymphotropic retrovirus-I exposure on cultured human glioma cell lines. AB - Four different human tumor cell lines of glial origin have been exposed to a human T lymphotropic retrovirus (HTLV-I). All these cell lines were positive for the glial marker glial fibrillary acidic protein (GFAP). The presence of virus RNA was demonstrated by in situ hybridization using an HTLV-I, SStI-SStI viral insert as probe. Virus expression has been monitored through an indirect immunofluorescence assay using a monoclonal antibody against virus core protein p19. All the four glioma cell lines tested became positive for p19 after 2 weeks of co-cultivation and showed a clear alteration of GFAP expression. PMID- 1882643 TI - The electron microscopic appearance of the beta-galactosidase reaction product. PMID- 1882644 TI - Fatal hemorrhage in a cerebral pilocytic astrocytoma-adult type. AB - A 69-year-old female presented with a 6-week history of left-sided weakness and a large cerebral mass on computed tomographic scan and magnetic resonance imaging. The patient subsequently had an acute intracerebral hemorrhage with uncal and tonsillar herniation. Postmortem examination revealed an acute cerebral hemorrhage from a pilocytic astrocytoma-adult type. These cerebral neoplasms are rarely associated with hemorrhage. PMID- 1882645 TI - Unfavorable outcome of adrenal medullary transplant for Parkinson's disease. AB - A 45-year-old woman with moderately severe parkinsonism underwent adrenal medullary autograft to the brain. The operation was performed in Mexico City. There were multiple post-operative complications, including worsening of the parkinsonism with almost complete loss of ability to communicate. Death from bronchopneumonia occurred 13 months after surgery. At autopsy the surgical tract was found to extend through the corpus callosum and into the thalamus on the opposite side. Residual necrotic adrenal tissue was found as a small round well defined mass in the ventricle loosely attached to the left fornix. This case emphasizes the obvious risks of this still experimental procedure and the difficulties in obtaining a surviving and functional adrenal medullary graft. PMID- 1882647 TI - Analysis of possible factors influencing the occurrence of occlusal tooth wear in a young Saudi population. AB - The purpose of this study was to attempt to correlate possible etiologic factors with the occurrence of occlusal tooth wear in a young Saudi population. The material comprised 90 individuals with a mean age of 22 years within a range of 19-25 years. A dentition wear index, in addition to anterior and posterior wear subindices were derived from tooth-by-tooth evaluations of casts. Factors found to correlate significantly with increased occlusal wear were bruxism, biting habits such as pen- and nail-biting, use of an indigenous chewing-stick called miswak, and high intake of fruit juices. There was no correlation between subjects from differing geographic and/or climatic habitats and the severity of tooth wear. The common element of a harsh desert terrain may constitute the dominant passive abrasive etiologic factor in the present sample. PMID- 1882646 TI - Release of fluoride and metal ions from root surfaces after topical application of TiF4, SnF2, and NaF in vitro. AB - Aqueous solutions of TiF4 cause a rapid uptake and a long-lasting retention of fluoride when applied to dentin. The aim of this study was therefore to investigate the pattern of fluoride release after TiF4 application in vitro, compared with SnF2 and NaF application. TiF4, SnF2, and NaF were applied for 4 min and 1 min to standardized areas of six groups of root surface specimens immersed in distilled water. Untreated specimens were used as controls. The water was changed daily for 30 days, and F concentrations measured by an ion-selective electrode. All test groups showed a rapid decline in F concentration. In the 4 min group F concentration more than double the detection limit of the F electrode could be registered the first 28 days for TiF4, 11 days for SnF2, and 7 days for NaF. In the 1-min group periods of F registration were shorter. Analysis of Sn by atomic absorption spectrophotometry showed decreasing concentrations in the first 12-day samples in the 1-min and 4-min groups. Traces of Ti were found in the first few samples, but no pattern of release could be observed. PMID- 1882648 TI - Dentofacial morphology in professional opera singers. AB - The interaction between muscle function and bone development has been studied mainly in animals. The aim of the present investigation was to study the dentofacial skeleton in individuals with a high degree of activity of muscles associated with the facial skeleton. It was assumed that a professional singer would constitute such an individual. Lateral cephalograms of singers from the Royal Opera Choir in Stockholm were studied and compared with lateral cephalograms of a control group. Significant differences between the singers and controls were found, such as length of mandible, length of maxilla, and increased facial height. The findings could be interpreted as an association between facial muscle hyperactivity and respiratory hyperfunction and dentofacial morphology. PMID- 1882649 TI - Acupuncture in treatment of facial muscular pain. AB - Forty-five individuals with long-standing facial pain or headache of muscular origin were randomly allocated into three groups. The first group was treated with acupuncture, the second group received an occlusal splint, and the third group served as controls. Both acupuncture and occlusal splint therapy significantly reduced subjective symptoms and clinical signs from the stomatognathic system. No differences between these two groups were found with regard to treatment effects. It is concluded that acupuncture is an alternative method to conventional stomatognathic treatment for individuals with craniomandibular disorders of muscular origin. PMID- 1882650 TI - Fluoride sources and dental attendance habits among adults in communities with optimal and low water fluoride concentrations. AB - The aim of this study was to obtain data on local fluoride supply, dental attendance, and dental care habits in two sociologically similar municipalities with optimal, 1.0 ppm, and low, 0.3 ppm, water fluoride concentrations, respectively. The participants in the study were 30- to 40-year-old lifetime residents in the two municipalities: 569 individuals from the 1-ppm fluoride community and 466 from the low-fluoride community. There were no intergroup differences in the fluoride mouthrinse utilization rate of 1%. Fluoride toothpaste was much more common in the low-fluoride area. In the 1-ppm fluoride area more people drank tea, and they went more regularly to the dentist. It is suggested that dental attendance habits and various fluoride sources should be taken into account in studies evaluating the effect of fluoride in drinking water. PMID- 1882651 TI - Is there a long-term caries-preventive effect of sugar restrictions during World War II? AB - Wartime decrease in caries prevalence among children explained by restrictions in sugar availability and consumption is widely documented. The aim of the present investigation was to study possible long-term effects of this regimen on dental caries. Norwegian age cohorts who were 7 years old during World War II were reexamined in 1983. On the basis of DMF recordings of their first permanent molars, a long-lasting beneficial effect of the wartime caries decrease could not be demonstrated. PMID- 1882652 TI - Gingival fluid and tissues around successful titanium and ceramic implants. A comparative clinical, laboratory, and morphologic study. AB - The gingival tissue reactions around 19 titanium implants (Branemark System) and 6 ceramic implants (Frialit) were studied by using established variables for monitoring periodontal status. Natural teeth in the same or the opposite jaw served as controls. Both clinical and laboratory examinations showed healthy gingival status. No differences in soft-tissue reactions between the two types of implant or between the implants and the natural teeth were registered. PMID- 1882653 TI - Effects of lysozyme-thiocyanate combinations on the viability and lactic acid production of Streptococcus mutans and Streptococcus rattus. AB - Effects of human lysozyme (HLZ) combined with thiocyanate (SCN-) ions on mutans streptococci, both in physiologic salivary concentrations, were studied. The bacteria were incubated for 75 min either in HLZ-supplemented sterilized human whole saliva (pH 5 and 7) or in neutral buffer in the presence or absence of HLZ (30 mg/l)-SCN- (1-5 mM) combinations. HLZ had no inhibitory effect on the viability of Streptococcus mutans, serotype c, either in saliva or in buffer, not even at pH 5, in the presence of salivary bicarbonate or in higher (up to 240 mg/l) concentrations of HLZ. In contrast, HLZ significantly decreased the viability of S. rattus in both media. HLZ also effectively blocked the lactic acid production of S. rattus but not that of S. mutans. Thiocyanate ions, which have been proposed to enhance the antimicrobial activity of lysozyme, did not affect the antibacterial activity of HLZ or HLZ-HCO3- combinations. It is concluded that the in vivo levels of SCN- ions, which constitute an integral part of the peroxidase antimicrobial system in saliva, may not be high enough to trigger the lysis of S. mutans by lysozyme in human saliva. The very low prevalence of S. rattus compared with S. mutans in human populations may be associated with their different susceptibility to lysozyme-mediated inhibition in saliva. PMID- 1882654 TI - Root surface reactions to TiF4 and SnF2 solutions in vitro. An ultrastructural study. AB - Previous studies have indicated that TiF4 and SnF2 differ in their demineralizing effect when applied topically to root surfaces at the same acidity. The aim of this study was to examine in more detail the outermost layer of root surface specimens by transmission electron microscopy (TEM) after short-term exposure to these acidic fluoride solutions. Root surface specimens were exposed for 1 min and 4 min to equimolar (1.1 M F) solutions of a) TiF4, native pH 1.0; b) SnF2, acidified to pH 1.0; and c) SnF2, native pH 2.5. The specimens were then rinsed in saline and processed for TEM. Exposure to TiF4 resulted in a partly demineralized zone 8-10 microns deep after 1 min and 5-27 microns deep after 4 min of application. A 0.1-micron-thick, electron-dense coating was present in all TiF4-treated specimens. Acidified SnF2 resulted in a completely demineralized zone, 4-7 microns deep, when applied for 1 min and 4 min, whereas SnF2 at native pH produced a 0.5- to 1.0-micron-wide partially demineralized zone. Unevenly distributed crystalline deposits were a frequent finding on SnF2-treated surfaces. The results indicate that solutions of TiF4 and SnF2 at native pH will cause only slight demineralization when applied topically to root surfaces. PMID- 1882655 TI - Acta sixty years ago. On abortions in Oslo, fistulas in Helsinki, elderly primiparas in Stockholm, and more. PMID- 1882656 TI - Smoking and childbirth. PMID- 1882657 TI - Surveillance of smoking during pregnancy in Sweden, 1983-1987. AB - Since 1982, prospective information on smoking during early pregnancy is reported to the Swedish Medical Birth Registry for nearly all (93%) women who give birth. The present paper studies the validity of this information: effects on birthweight and perinatal mortality are very similar to those described previously in the literature. For each parity class, smoking decreases in inverse proportion to increasing maternal age; for each maternal age class, smoking increases with parity. A slight reduction in smoking rate is observed between 1983 and 1987, most pronounced for young women. There are marked geographic and social differences in the rate of smoking during pregnancy. This dataset can be used in the future to monitor the prevalence of smoking, and to study various factors associated with smoking and the impact of countermeasures taken against smoking during pregnancy. It can also be used to study possible associations between maternal smoking and rare events like congenital malformations and child cancer. PMID- 1882658 TI - Fetal and infant outcome of pregnancies with very early rupture of membranes. AB - Fetal and infant outcome was studied in 38 singleton pregnancies complicated by very early rupture of membranes (PROM), in gestational weeks 19-29, over a 4-year period, in a Swedish population. The pregnancies were managed according to a specified protocol, including postponement of delivery until 34 weeks of gestation if possible. Stillbirth occurred in 10 cases (26.3%), all with PROM before 26 completed weeks, while 6 other infants died in the neonatal period. Respiratory distress syndrome was evident in half (50.0%) of the 28 liveborn infants. The surviving 22 infants (57.9%) were followed up to 2 years of age. The rate of neurological sequelae at follow-up was 22.7% (5/22). The fetal outcome of the 20 pregnancies with rupture of membranes before 26 completed weeks was poor; only 7 infants of the 10 born alive survived the neonatal period. The short-term fetal outcome in the group with rupture of membranes in 26-29 completed weeks was better: 15 of the 18 infants survived, but 4 had neurological sequelae. PROM before 29 completed weeks of gestation is associated with severe short-term and long-term fetal complications, in cases where the pregnancy is prolonged for several weeks. PMID- 1882659 TI - Survival of chlamydiae in human semen prepared for artificial insemination by donor. AB - Semen specimens from 21 men with urethral infection with Chlamydia trachomatis were tested for the presence of the organism before and after cryopreservation for 3 weeks of storage at -196 degrees C. Five specimens were chlamydia-positive before preservation and four of them were still positive after storage when examined by enzyme immunoassay (Chlamydiazyme). When examined by cell culture, four proved chlamydia- positive before storage and two afterwards. The results indicate that testing for C. trachomatis has to be performed from the urethra of all donors of semen used for artificial insemination before the inoculation takes place. PMID- 1882660 TI - A health care program for the investigation and treatment of elderly women with urinary incontinence and related urogenital symptoms. AB - The assessment and treatment of urinary incontinence and related urogenital symptoms using an algorithm model was evaluated in 364 elderly women complaining of urinary incontinence. The women (age 72.1 +/- 1.5 years, range 65-84 years) were assessed by a 48-hour pad test, a cough provocation test, micturition lists and a gynecological examination which included a smear test, measurement of vaginal pH and bacterial cultures. The diagnosis of urinary incontinence was confirmed in 346 women (stress 26.3%; urge: 32.7%; mixed: 41.0%). Women suffering from stress incontinence were younger (p less than 0.05) and had experienced a larger number of deliveries (p less than 0.05) than women with urge incontinence. All the women were treated with oral estriol, 3 mg daily for 4 weeks followed by 1-2 mg daily. The total urinary leakage per 48 hours (p less than 0.01) and maximum single leakage (p less than 0.05) were reduced in women with mixed incontinence, while the frequency of micturition decreased (p less than 0.05) in women with urge incontinence after 12 weeks treatment with oral estriol. There were no significant changes in any of the objective micturition parameters in women with stress incontinence following treatment. Karyopyknotic index and the presence of lactobacilli were increased (p less than 0.001), and vaginal pH decreased (p less than 0.001) following treatment in women with all types of incontinence. More than 70% of all the women treated in this algorithm model judged themselves to be improved, much improved or cured. PMID- 1882661 TI - A randomised, double-blind, placebo-controlled trial of gemeprost (Cervagem) pessaries for cervical dilatation in non-pregnant women. AB - In a randomised, double-blind trial, 75 women received either placebo or a 1-mg gemeprost (Cervagem) pessary for cervical dilatation prior to gynecological procedures which require mechanical dilatation of the cervix. No significant difference was seen between gemeprost and placebo with respect to preoperative cervical dilatation. The incidence of vaginal bleeding and adverse effects was similar in each group. PMID- 1882662 TI - Is diathermy safe in women with copper-bearing IUDs? AB - Ultrasound and short-wave diathermy are widely used in physiotherapy to induce heating of deep tissues, since this causes a concomitant increase in local blood flow. A metallic implant in the treated field is generally regarded as a contra indication to diathermy because of the risk of thermodamage to surrounding tissues. It is not certain, however, if copperbearing IUDs contain sufficient metal as to constitute a risk. In order to exclude the possibility that diathermy might lead to intra-uterine burns in women using copperbearing IUDs a technique was devised of measuring temperatures in the copper wire of an IUD in situ during short-wave an ultrasonic therapy. The results indicate diathermy to be perfectly safe in women whit copper-bearing IUDs. PMID- 1882663 TI - Tubulo-villous adenoma of the female genital tract: a case report and review of literature. AB - A case is presented of tubulo-villous adenoma in the vagina of a 43-year-old woman. The possible origin of this rare condition is discussed and the need for careful follow-up is emphasized. PMID- 1882664 TI - Sarcoidosis of the uterus. AB - Sarcoidosis rarely involves the female genital tract. A report is presented of 2 cases of sarcoidosis of the uterus. In the first, the diagnosis was made by biopsy of the portio vaginalis uteri which was amputated during the Manchester operation for genital prolapse. In the second case the diagnosis was made by endometrial curettage for postmenopausal vaginal bleeding. Neither of the women exhibited signs of generalized sarcoidosis. PMID- 1882665 TI - Angiosarcoma of the vagina. A light and electronmicroscopy study. AB - A 73-year-old woman, whose medical history reported radical hysterectomy and radiotherapy for squamous cell carcinoma of the cervix uteri 20 years earlier, was found to have an angiosarcoma of the vagina. The histological diagnosis was confirmed by immunohistochemical staining of tumor cells for factor VIII-related antigen and ultrastructurally defined vasoformative structures. Primary angiosarcoma of the vagina is quite rare and reported in only two published cases. The present case is a third in general, and the first report confirmed by light microscopy, immunohistochemical, and electronmicroscopy studies. PMID- 1882666 TI - The infected knee arthroplasty. A 6-year follow-up of 357 cases. AB - The incidence of deep infection after 12,118 primary knee arthroplasties performed in Sweden from October 1, 1975 through 1985 with a median follow-up of 6 years was 1.7 percent for arthrosis and 4.4 percent for rheumatoid arthritis. Risk factors for infection were large prostheses, postoperative wound-healing complications, rheumatoid arthritis, a prior deep infection, and skin infections. We have analyzed the treatment of 357 knee arthroplasties with a deep infection. Systemic antibiotics alone were primarily used in 225 knees, with healing of the infection in 44 knees, 20 of which had a functioning prosthesis at the final follow-up; the treatment did not compromise later revision surgery. Soft-tissue surgery was used in 154 knees--37 healed, 15 of which had a functioning prosthesis. Resection arthroplasty resulted in healing of the infection in 11 of 22 knees. Revision arthroplasty was performed in 107 knees, with eventual healing of the infection in 81 knees, 36 of which had a functioning prosthesis; there were no differences in the outcome of one-stage and two-stage procedures. Arthrodesis was attempted in 135 knees, with eventual healing of the infection in 120 knees and fusion in 105. Twenty-two patients were amputated. Thus, the infection healed in 315 knees (88 percent), but only 71 (20 percent) recovered with a functioning prosthesis, and 8 patients died of the infection. Attention should therefore focus on prophylactic measures directed towards the soft-tissue problems--by avoiding conflicting skin incisions, by gentle handling of the periarticular soft tissues, by avoiding the use of constrained prostheses and oversized compartmental prostheses, by letting wound healing take priority over motion in knees with compromised soft tissues, and by using prophylactic antibiotic treatment for skin ulcers until these have healed. PMID- 1882667 TI - Soft-tissue procedures for the exposed knee arthroplasty. 18 cases followed for 7 (1-17) years. AB - Reconstructive surgery was performed in 18 knee arthroplasties because of wound healing problems or skin necrosis. The procedure, after debridement, included myocutaneous, muscle flap, and split-skin grafts. Revision was necessary in 6 cases. After 1-17 years, 6 patients had died, 2 had had a low femur amputation, and 5 had had an arthrodesis. Five patients had retained the prosthesis, although 3 of them had considerable pain and poor mobility; only 2 patients were tolerably painfree and had acceptable mobility. Patients with an exposed knee endoprosthesis should be referred to centers with special competence in plastic reconstructive surgery. PMID- 1882668 TI - Synovectomy for septic arthritis. Early versus late synovectomy studied in the rabbit knee. AB - Thirty rabbits with established unilateral septic arthritis of the knee after inoculation with Staphylococcus aureus received cloxacillin 50 mg/kg x 2 i.m. and probenecid 250 mg x 1 p.o. from Day 3 to 21. In 26 knees, synovectomy was performed 3, 5, and 7 days after the inoculation, and four knees were not operated on. Further, synovectomy was performed in eight noninfected knees. The rabbits were killed 3 or 7 weeks after the operation, and the specimens were examined macroscopically and microscopically. All the cultures taken postoperatively and at killing were negative. Infected knees synovectomized on Day 3 differed, although marginally, 3 weeks postoperatively from the operated on, uninfected group; a minor loss of cartilage cellularity and glycosaminoglycans was observed, but there were no changes indicating arthrosis. At 7 weeks postoperatively, this difference was more pronounced. If synovectomy was performed at a later stage, increased destruction was observed: after 7 days of infection, all the knees presented cloning and vascular crossing of the tidemark, indicating arthrosis, which did not differ from those knees treated with only antibiotics. We conclude that synovectomy performed early in the course of infection may stop the destructive influence of enzymes and of the synovial membrane leading to irreversible changes in the cartilage. PMID- 1882669 TI - Articular cartilage changes following meniscal lesions. Repair and meniscectomy studied in the rabbit knee. AB - A well-defined, longitudinal lesion in the avascular part of the medial meniscus of the right knee was made in 30 rabbits. After 3 months, the lesion was repaired surgically in 12 rabbits, was untreated in 12 rabbits, and a meniscectomy was performed in 6 rabbits. The articular cartilage was studied macroscopically and microscopically at 3-month intervals. Cartilage changes 3 months after meniscectomy were more pronounced than after meniscal repair or than in untreated lesions. However, meniscal repair did not reverse the cartilage changes. PMID- 1882670 TI - Complications of leg lengthening. 46 procedures in 28 patients. AB - The results and complications of 46 leg-lengthening procedures in 28 consecutive patients were analyzed retrospectively. There were 24 femoral and 22 tibial lengthenings, performed for short stature (5 patients) and limb-length discrepancy (23 patients). Three methods were used: diaphyseal osteotomy, metaphyseal corticotomy, and distraction physiolysis. In the second group a satisfactory result was obtained more often and a lower complication rate was observed. The overall complication rate was high: 45 substantial problems occurred. We conclude that leg lengthening is difficult, requiring good preoperative examination and planning, and should be carried out only in specialized centers. PMID- 1882671 TI - Intracapsular pressure in hip synovitis in children. AB - Scintimetry and intracapsular pressure recordings were performed in 10 painful hips in children. Maximum intracapsular pressures were recorded with the hip in extension or in 90 degrees of flexion. Minimum pressures were recorded with the hip in semiflexion. Extremely high pressures were recorded in extension/maximum internal rotation. In 3 cases the pressure exceeded the estimated systolic blood pressure. There was a close correlation between the volume of aspirated fluid and intracapsular pressure. In a case of septic arthritis, ischemia in the epiphysis was noted scintigraphically. This ischemia was reversed following decompression by aspiration. PMID- 1882672 TI - Effect of intracapsular hyperpressure on femoral head blood flow. Laser Doppler flowmetry in dogs. AB - Intracapsular hyperpressure in the hip joint of dogs affected femoral head blood flow, especially in the juvenile animals. Graphic recording of the laser Doppler signal curve using rapid sampling time demonstrated venous hip joint tamponade in both juvenile and adult dogs. Laser Doppler flowmetry seems to be a sensitive and reproducible method to demonstrate femoral-head blood-flow changes. PMID- 1882673 TI - Interlocking nailing of distal femoral fractures. 28 patients followed for 1-2 years. AB - We treated 28 fractures of the distal femur with a Grosse-Kempf interlocking nail, and the patients were followed for at least 1 year. Five fractures did not unite, and the rest healed after 5 (3-7) months. Nail breakage was the most serious complication; and the more distal the fracture was, the more easily the nail broke. With the addition of a cast brace and protected weight bearing, a locked nail is a good type of fixation for distal femoral fractures down to 4 cm above the condyles. PMID- 1882674 TI - Ipsilateral femoral neck and shaft fractures. Retrospective study of 33 cases. AB - Forty-two consecutive adult patients with a concomitant ipsilateral femoral neck and shaft fracture were treated. The neck fracture was initially missed in 7 patients. Surgery was delayed for a median of 7 days because of the patients' poor general conditions. Thirty-three patients were followed up for 2 (1-6) years. All 33 necks healed, with a union period of 3.3 +/- 1.7 months; and 28 shafts healed after 7.9 +/- 1.8 months. Thus, the femoral shaft determined the total union rate and union period. All the complications, (eight out of 33) occurred in the open procedure group. Our series reveals that ipsilateral femoral neck and shaft fractures have a relatively satisfactory outcome. Closed Kuntscher's nailing or interlocking nailing with supplementary Knowles' pinning is the preferable technique. PMID- 1882675 TI - Fracture healing of chick femurs in tissue culture. AB - Embryonic chick femurs were isolated, and a transverse osteotomy was performed at the midshaft. The femurs were transplanted individually onto the host chorioallantoic membrane and incubation continued. Cultured femurs were harvested at intervals from 1 to 9 days after the transplant. Histologic examinations showed that repair progressed rapidly: the fracture gap was invaded by blood vessels and fibrous ingrowth. Ossification followed, and the repair process was completed by Day 9. PMID- 1882676 TI - Carbon fiber for repair of the rotator cuff. A 4-year follow-up of 14 cases. AB - Thirteen patients with 14 large rotator cuff tears were operated on using carbon fiber to cover the defect. The median follow-up time was 4 years. In 11, 1, and 2 cases the results were respectively excellent or good, fair, and poor. In 2 cases where the carbon fiber was anchored to the major tuberosity, a bone cyst was seen, but it did not influence the result. A carbon fiber tow application combined with Neer's anterior acromioplasty seems useful in the reconstruction of large tears of the rotator cuff. PMID- 1882677 TI - Tension-band wiring of olecranon fractures with nonsliding pins. Report of 20 cases. AB - Twenty consecutive patients with displaced fractures of the olecranon were operated on using the tension-band wiring technique with a nonsliding pin. The patients were followed until clinical and radiographic healing or removal of the implant. Healing was uneventful in 19 patients after a median of 6 weeks. Redislocation occurred in 1 patient with a severely comminuted fracture. The design of the nonsliding pin eliminates outward pin migration, as well as migration into the medullary canal. PMID- 1882678 TI - Piroxicam-induced reduction in osteopenia after external fixation of rabbit tibia. AB - Twelve rabbits were treated with a unilateral external fixator in one tibia for 12 weeks, while the other tibia served as an intact control. Half of the animals were also treated with 10 mg/kg/day of piroxicam, given in two daily oral doses. Changes in bone mineral content were determined using single photon absorptiometry. After 12 weeks, we found a 3 percent decrease in the bone mineral content in the tibia of the animals treated with piroxicam versus 9 percent in the nonpiroxicam group (P = 0.04). In the femurs, there was an insignificant decrease in bone mineral, 2 percent (piroxicam) and 1 percent (nonpiroxicam) respectively. The results indicate that piroxicam may reduce the osteopenia caused by external fixation. PMID- 1882680 TI - Talectomy for equinovarus deformity in arthrogryposis. A 13 (2-20) year review of 17 feet. AB - Ten children (17 feet) with arthrogryposis multiplex congenita and severe, rigid equinovarus deformity underwent talectomy to bring the foot plantigrade. One child had a bilateral talectomy after only one manipulation, whereas the others were operated on an average of three times before talectomy. After a mean follow up of 13 years, 14 out of 17 feet were satisfactory. We recommend that children with arthrogryposis and severe rigid equinovarus deformity be treated with talectomy before the expected age of walking. PMID- 1882679 TI - Locomotor problems in infantile facioscapulohumeral muscular dystrophy. Retrospective study of 9 patients. AB - A retrospective study of 9 patients with infantile facioscapulohumeral muscular dystrophy defines orthopedic deformities and progression. Patients presented in the early months of life with facial diplegia. Sensorineural hearing loss occurred in 8 out of 9 with a mean onset at 5 (2-9) years. Walking began at the normal time, but worsened progressively, which was due mainly to gluteus maximus muscle weakness. Scapular winging, extreme lumbar lordosis, and foot drop were characteristic. The majority of patients (in this and other series) lose walking ability in the second decade. Efforts to control lumbar lordosis by bracing while the patients were still walking were ineffective. Control of lumbar lordosis after the patients are wheelchair-dependent is important. PMID- 1882682 TI - Devitalizing effects of phenol on bone marrow cells. Histologic study on cadaveric animal vertebrae. AB - The devitalizing effects of 5-90 percent phenol for 30 seconds on bone marrow cells were examined on vertebral bodies of fresh animal cadavers. Evaluation was made by measuring the width of the zone of necrotic cells. The zone increased with rising phenol concentration up to 75 percent, reaching an average width of 0.75 mm. However, when protected by bone trabeculae, the cells escaped devitalization. PMID- 1882681 TI - Spondyloenchondrodysplasia. A rare cause of short-trunk syndrome. PMID- 1882683 TI - Blood flow in chronic Achilles tendinosis. Radioactive microsphere study in rabbits. AB - Cerium-labeled microspheres were used for blood-flow measurements in 7 New Zealand white rabbits with exercise-induced chronic Achilles paratenonitis and tendinosis. The blood flow increased 1.9 times more on the exercised side as compared with the contralateral, unexercised (control) side with respect to both the tendon and the paratenon. The blood flow of the tendon of the exercised leg showed a strong correlation with the blood flow in the paratenon of the ipsilateral side (r = 0.81). We concluded that the relative contribution of blood from the paratenon to the tendon remained unaltered in the exercised tendon and that degeneration of the tendon cannot be primarily explained by chronic circulatory impairment. PMID- 1882684 TI - Diagnostic external fixation of two carpal bones. A technical note. AB - Ulnar midcarpal instability can be treated by ligament repair or by a partial arthrodesis between the triquetrum and the hamate. If a partial arthrodesis is planned, we perform an ultimate diagnostic test to determine whether or not a subsequent definitive partial arthrodesis would be effective in controlling the feeling of weakness and instability. PMID- 1882685 TI - Sacral osteomyelitis due to Nocardia asteroides. A case report. AB - Nocardial osteomyelitis is increasing in both immunocompetent and immunosuppressed patients. We report a case of a Nocardia asteroides infection of the sacrum in a 37-year-old man who was successfully treated surgically. PMID- 1882686 TI - Ganglion causing paralysis of the suprascapular nerve. Diagnosis by MRI and ultrasonography. AB - A 26-year-old man had a right infraspinatus muscle weakness and aching of the shoulder due to suprascapular nerve entrapment confirmed by electromyography. MRI revealed a well-defined area of increased signal intensity over the suprascapular notch. An ultrasonogram showed a homogeneous hypoechogenic area at the base of the scapular spine. A diagnosis was made of a ganglion compressing the inferior branch of the suprascapular nerve. After removal of several ganglia, the patient had immediate pain relief, and normal electromyographic findings were obtained 5 months postoperatively. PMID- 1882687 TI - Transscaphoid perilunate dislocation with a dorsal dislocated proximal scaphoid fragment. Report of 2 cases. AB - Two patients with a dorsal transscaphoid perilunate dislocation with a dorsal dislocation of the proximal fragment of the scaphoid are described. Our 2 cases demonstrate that there can be a simultaneous fracture of the scaphoid and rupture of the scapholunate ligaments, which require open reduction and internal fixation. PMID- 1882689 TI - Simultaneous fracture of the ankle and disruption of the superior tibiofibular joint. A case report. AB - We report a case of fracture-dislocation of the ankle occurring together with a disruption of the superior tibiofibular joint. The simultaneous occurrence of these two lesions does not seem to have been reported previously. PMID- 1882688 TI - Transstyloid perilunate carpal dislocation. A case report. PMID- 1882690 TI - Patellar pain. PMID- 1882691 TI - Suicide on the paternal and maternal sides of depressed patients with a lifetime history of attempted suicide. AB - The computational model of Slater, based on the analysis of ancestral secondary cases on the paternal and maternal sides of the subjects, was applied to depressed patients with a lifetime history of attempted suicide, either violent or nonviolent, in order to investigate possible modes of transmission of suicidal behavior. Among 549 patients, 15 had 2 or more ascendant first- and second-degree relatives who committed suicide. The results of the distribution of these cases were compatible with polygenic inheritance of suicidal behavior in depressed patients with a history of attempted suicide. In patients using violent methods, a significantly greater loading of ancestral secondary cases of suicide was observed on the maternal side and, in the nonviolent attempter group, on the paternal side. PMID- 1882692 TI - Suicide risk varies by subtype of affective disorder. AB - A cohort study of mortality was conducted in which 4022 patients with affective disorder who were treated during 1976-1985 in a mental institution or community clinic operated by the province of Alberta, Canada, were followed to the end of 1985. Vital status was determined by record linkage to the Statistics Canada Mortality Data Base. There were 326 deaths altogether, 96 from suicide. The standardized mortality ratio (SMR) for all causes of death combined was 2.3, and for suicide the SMR was 26.0. The SMR was also elevated for mental, circulatory and respiratory disorders, but not for neoplasms. The principal objective of the study was to determine whether there was a gradient of increasing mortality risk across the following diagnostic subgroups: manic disorder, bipolar affective disorder and major depressive disorder. A trend was found for suicide but not for all causes of death combined. The pattern of risk persisted after adjustment for the covariates sex, age and marital status in a Cox regression analysis. PMID- 1882693 TI - Sexual abuse of girls: aspects of the genesis of mental disorders and therapeutic implications. AB - We studied the mental disorders of 33 women with a history of intrafamilial sexual abuse as a child and found a wide range of psychopathological symptoms, but no typical incest syndrome. Several psychosocial factors are presented and the psychodynamics of and the causative circumstances initiating the mental disorders are discussed. These circumstances were mainly situations of separation, which led to ego instability and gave rise to a feeling of helplessness and impotence. The necessity to take into consideration the possibility of sexual abuse during childhood in all cases of mental disorders as well as therapeutic guidelines are discussed. PMID- 1882694 TI - Suicide and other causes of death in a five-year follow-up of patients treated for self-poisoning in Oslo. AB - This 5-year follow-up study includes all patients (n = 934; 50% females) treated for self-poisoning in Oslo during 1 year. Seventeen percent were considered suicide attempts upon admission, 25% among the nonabusers and 8% among the abusers. At follow-up, 122 patients were dead (61% males). The mortality rate was highest among the abusers. The mortality rate was similar (13%) among those who were considered to be suicidal on admittance and those who were not. The causes of death were suicide (28%), opiate abuse (16%), heart disease (14%), accidents or wounds (11%), alcoholism (9%) and others (22%). The standard mortality rate was highly increased in all groups (8 times on average), highest among the female opiate abusers, whose rate was 63 times higher than expected. The increased suicide rates (87 times for females, 27 times for males), however, may be a more relevant measure of mental morbidity than the standard mortality rate. Logistic regression analysis demonstrated that male sex, age above 50 years and the lowest social group were factors on admission associated with death in the follow-up period. Age above 50 years and suicidal attempt on admission were associated with subsequent suicide. The study strongly supports the idea of self-destructiveness and slow suicide in substance abuse. PMID- 1882695 TI - Latencies of the P300 component of the auditory event-related potential in depression are related to the Bech-Rafaelsen Melancholia Scale but not to the Hamilton Rating Scale for Depression. AB - The relationship between severity of depression and the P300 latency of auditory event-related potential was investigated in 36 patients with a major depressive episode according to DSM-III. Positive correlations were found between of the P300 latency and the total score of the Bech-Rafaelsen Melancholia Scale (BRMS), the 4 retardation items of the BRMS (motor, verbal, intellectual and emotional) and the item for lowered mood. In contrast, latencies were not associated with the scores of the Hamilton Rating Scale for Depression, which considers retardation to a lesser extent than the BRMS. PMID- 1882696 TI - Cerebrospinal fluid acetylcholinesterase in patients with dementia associated with schizophrenia or chronic alcoholism. AB - Cerebrospinal fluid (CSF) acetylcholinesterase (AChE) was determined for 11 chronic schizophrenic patients with dementia, 9 patients with dementia associated with alcoholism and 8 age-equivalent control subjects. The AChE levels in both patient groups were unrelated to the degree of cognitive decline and they were in the same range as in the control group. In schizophrenic patients no relationship was found between CSF AChE and the severity of psychotic symptoms. Our results suggest that dementia may occur in these patient groups without CSF AChE involvement. PMID- 1882697 TI - Low brain uptake of L-[11C]5-hydroxytryptophan in major depression: a positron emission tomography study on patients and healthy volunteers. AB - The precursor of serotonin, L-5-hydroxytryptophan (L-5-HTP), was radiolabelled with 11C in the beta-position, yielding [beta-11C]serotonin after decarboxylation, allowing positron emission tomography studies of L-5-HTP uptake across the blood-brain barrier. We studied 8 healthy volunteers and 6 patients with histories of DSM-III major depression, 2 with repeated examinations after clinically successful treatment. We report a significantly lower uptake of [11C]5 HTP across the blood-brain barrier in depressed patients, irrespective of phase of illness. The findings emphasize that serotonin is involved in depressive pathophysiology and support earlier suggestions that the transport of 5-HTP across the blood-brain barrier is compromised in major depression. PMID- 1882698 TI - Lithium alone or in combination with carbamazepine for the treatment of rapid cycling bipolar affective disorder. AB - The authors retrospectively examined the clinical outcome (after 1, 2 and 5 years of beginning the therapeutic protocols) for 16 rapid-cycling bipolar affective disorder patients given either lithium alone or lithium plus carbamazepine. The results suggest that both therapeutic protocols have been safe and clinically effective. However, improvement was observed earlier in the patients given lithium and carbamazepine. PMID- 1882699 TI - Alcohol abuse among elderly patients in a general hospital as identified by the Munich Alcoholism Test. AB - The aim of this study was to assess the prevalence of alcohol abuse among elderly patients in a general hospital. Scores on the Dutch version of the Munich Alcoholism Test (MALT) and medical records were obtained from 132 patients aged 65 and over, staying at the University Hospital Leiden. According to the MALT, 9% of the elderly patients (13% of the men and 7% of the women) were classified as alcoholics. In contrast, the discharge diagnosis involved alcohol dependence or abuse for only 0.5% of the patients 65 years and over admitted in 1989. In this study, two thirds of the alcoholic patients were recognized by the attending physician. Vague symptoms as admission diagnosis occurred more frequently in alcoholics than in nonalcoholics. Regarding former medical diagnoses, alcoholics had suffered significantly more often from organic brain diseases. In comparison to nonalcoholics, elderly alcoholics used more psychotropic drugs. PMID- 1882700 TI - Mental disorders in first-degree relatives of schizophrenics. AB - A total 215 first-degree relatives of 88 twin probands with schizophrenia, mood disorders and nonaffective psychoses were studied. The twins' parents and siblings were personally interviewed with structured diagnostic instruments and diagnosed in accordance with DSM-III-R criteria. The first-degree relatives were interviewed by interviewers who were blind to the twins' diagnoses. Schizophrenia and schizotypal personality disorder were significantly more frequent in first degree relatives of schizophrenic twins. Respectively, anxiety and mood disorders were significantly more prevalent among the parents and siblings of probands with mood disorders. Schizophrenic spectrum disorders were significantly more common in the families of schizophrenic probands compared with relatives of mood disorder probands, thus confirming a relationship between schizophrenia and schizophrenic spectrum disorders. However, we cannot, based on our study, specify whether this relationship is caused by genetic or environmental factors. PMID- 1882701 TI - Predicting course and outcome in delusional psychoses. AB - Eighty-four of 90 patients with delusional syndromes of different nosological attribution underwent a 7-year follow-up. From 179 items covering the whole spectrum of psychiatric description of index examination, 20 were found to be statistically significant in predicting different aspects of course and outcome by stepwise discriminant analysis. Course and outcome were defined by 6 criteria (course of illness, course of delusion, development of deficiency, length of inpatient care, adequate activity and social adjustment) encompassing separate (but only partly independent) aspects of a disorder. In contrast to the literature, clinical and psychopathological variables have major prognostic weight for different psychopathological as well as psychosocial aspects of outcome. Ten of the 20 significant items cover psychopathology, 4 pre-index course, 3 precipating events, 2 data from childhood, and 1 premorbid personality. Our results stress the importance of sensitive data collection and a clear separation of different outcome variables. PMID- 1882703 TI - Chemiluminescent 10-methyl-acridinium-9-(N-sulphonylcarboxamide) salts. Synthesis and kinetics of light emission. AB - 10-Methyl-acridinium-9-(N-sulphonylcarboxamide) salts are prepared via acylation of sulphonamides with acridine-9-carboxylic acid chloride and subsequent N alkylation with methyl triflate. Substituents on the sulphonamide component were varied to show the effect of steric and electronic factors on the kinetics of light output. The lifetime of the chemiluminescence light output ranged from 1 to 50 seconds for the 15 compounds reported. The long-term stability of the new compounds was superior to the phenyl ester counterparts. PMID- 1882702 TI - Sixth mycelial fraction acetone (6-MFA), an interferon inducer modulates acrylamide neurotoxicity. AB - A single i.p. administration of an immunomodulatory agent 6-MFA (a biological response modifier and antiviral agent of fungal origin, 10 mg/100g b.wt.), on 5th day of repeated acrylamide (ACR, 50 mg/kg b.wt.) treatment significantly protected rats against its specific neurotoxic effects. Corpus striatal 3H spiperone binding elevated (24%) while glutathione-S-transferase (GST) activity decreased (33%) in ACR group but values were markedly restored in 6-MFA alone and co-exposed group. Development of hind limb paralysis was also protected by 6-MFA. Results warrant the possible involvement of immune mechanisms and certain other factors such as lymphokines, hormones and microglia at the target site, which in turn facilitate the repair mechanism suggesting a therapeutic role of 6-MFA in clinical cases of toxic neuropathies in future. PMID- 1882704 TI - Luminol-dependent chemiluminescence in bovine eosinophils and neutrophils: differential increase of intracellular and extracellular chemiluminescence induced by soluble stimulants. AB - Luminol chemiluminescence was used to detect activation of the respiratory burst oxidase in bovine eosinophils and neutrophils. Extracellular and intracellular chemiluminescence were measured by supplementing the medium with horseradish peroxidase and catalase, respectively. Pure bovine eosinophils (greater than 90%), maximally stimulated with 1 nmol/l phorbol 12-myristate-13-acetate (PMA) showed ten times more extracellular luminol-dependent chemiluminescence (CL) than maximally stimulated pure bovine neutrophils (greater than 96%). Extracellular CL from eosinophils was preferably induced over intracellular CL by both PMA (27 fold difference) and platelet-activating factor (PAF) at 2 mumol/l (9-fold difference), but not by calcium ionophore A23187 (15 mumol/l). Time course information was used in the following experiments to distinguish between the mode of action of various stimulants. A progressively longer lag period was observed in eosinophil suspensions treated with decreasing doses of PMA, whereas platelet activating factor induced a dose-dependent increase in the maximum response with no change in time to peak CL. The time course of extracellular CL was almost identical to intracellular CL for all stimulants tested, providing no evidence to suggest that extracellular CL stems from a different enzyme system than intracellular CL. Eosinophils generated most extracellular CL when stimulated with PMA, whereas neutrophils were most efficiently stimulated with A23187, which induced intracellular CL in eosinophils as well as in neutrophils. This accords with the greater tendency of neutrophils to ingest and kill microorganisms, whereas eosinophils are armed to destroy large extracellular targets. PMID- 1882705 TI - A luminometric method for the determination of ATP and phosphocreatine in single human skeletal muscle fibres. AB - A sensitive method for the analysis of ATP and phosphocreatine (PCr) in single human skeletal muscle fibres is described. Muscle tissue was freeze-dried and single fibres were dissected free with the aid of low-power microscopy. The fibres were then extracted in trichloroacetic acid and neutralized with KHCO3. The assay is based on the continuous monitoring of light produced as a result of ATP degradation in the firefly luciferase reaction. PCr is measured as the amount of ATP formed in the creatine kinase reaction. The coefficient of variation was less than 4% for both ATP and PCr determination. The amount of tissue required for the assay is approximately 0.5 microgram (dry weight). The assay showed good agreement with spectrophotometric and high-performance liquid chromatographic (HPLC) measurements made upon extracts of whole muscle tissue. PMID- 1882706 TI - Bovine serum albumin interacts with bacterial luciferase. AB - Bovine serum albumin (BSA) affects the amount of light obtained from bacterial luciferase by competing with luciferase for one of the luciferase substrates, the aldehyde. At low aldehyde concentrations BSA behaves as an inhibitor, but at high aldehyde concentrations BSA relieves substrate inhibition. BSA reversibly binds decanal with a Ksi = 3.36 mumol/l, approximately half the affinity of luciferase for decanal (KM = 1.5 mumol/l). BSA also increased the rate of intermediate II dark decay. The data suggest that this involves a direct protein-protein (BSA luciferase) interaction. PMID- 1882707 TI - Research on bio- and chemiluminescence in the Soviet Union. PMID- 1882708 TI - Measurement of rate constants for quenching singlet oxygen with a Cypridina luciferin analog (2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo [1,2-a]pyrazin 3-one) and sodium azide. AB - The rate constants for [1O2] [MCLA] and [1O2] [NaN3] were measured by quenching the near-infrared emission (1 delta g----3 sigma g) in steady state with MCLA and NaN3, respectively. 1O2 was constantly generated by energy transfer to O2 from Ar laser-excited Rose Bengal. The Stern-Volmer plots yielded the second-order rate constants of 2.94 x 10(9) M-1 S-1 and 3.83 x 10(8) M-1 S-1 for quenching 1O2 with MCLA and NaN3 in water at pH 5.4, respectively. The 1O2 + MCLA reaction emitted light with maximum at 465 nm at pD 4.5 identical to the O(2-) + MCLA reaction. PMID- 1882709 TI - Direct chemiluminescence immunoassay (CLIA) for muramyl tripeptide phosphatidyl ethanolamine in plasma. AB - A competitive chemiluminescent immunoassay for quantitation of muramyl tripeptide phosphatidyl-ethanolamine (MTP-PE) in plasma has been developed. The assay is based on the use of an acridinium ester-labelled analogue of muramyl tripeptide and a rabbit antiserum. It includes an overnight incubation and a separation with a second antibody covalently coupled to paramagnetic particles. The sensitivity of detection is 0.012 nmol/l, the assay working range is 0.1-5 nmol/l, and the inter-assay CVs are less than or equal to 10%. Using up to 6000-fold sample dilutions, a wide working range (0.1-30,000 nmol/l) is obtained. Rat plasma samples were collected during and one day after intravenous infusion of MTP-PE. Following infusion, the concentrations in plasma declined multiphasically. Half life time was 0.37 h +/- 0.03 (mean +/- SD, alpha phase) and 1.76 h +/- 0.08 (mean +/- SD, beta phase), clearance and volume of distribution were 0.09 +/- 0.02 l/h x kg (mean +/- SD) and 0.06 +/- 0.01 l/kg (mean +/- SD) respectively. The use of an acridinium ester as a chemiluminescent (CL) label overcomes the problems associated with reagents of limited shelf-life. PMID- 1882710 TI - The effects of N-ethylmaleimide on extracellularly and intracellularly generated chemiluminescence in neutrophils indicate that the rate of deactivation of NADPH oxidase is higher when the oxidase system is localized on the plasma membrane than when it is localized on the phagosomal membrane. AB - Sustained generation of reactive oxygen metabolites following respiratory burst activation in neutrophils is a result of continued replenishment of a pool of active NADPH-oxidase. The sulphydryl-modifying reagent N-ethylmaleimide (NEM) has been shown to be without effect on the turnover of activated NADPH-oxidase but to inhibit the replenishment of active oxidase molecules (Akard et al., 1988). NEM was thus used to determine the rate of deactivation of extracellularly and intracellularly generated chemiluminescence in human neutrophils. We have shown that deactivation is more rapid when activation leads to a release of oxygen metabolites (extracellular chemiluminescence) than when the metabolites are generated intracellularly. The results indicate that the rate of deactivation of NADPH-oxidase is higher when the oxidase system is localized on the plasma membrane than when it is localized on the phagosomal membrane. PMID- 1882712 TI - The Clinical Cooperative Trial. Guide to a critical approach. AB - The growing difference with regard to academic and professional accountability between neurosurgeons and neuroscience is alarming. Controlled clinical trials continue to be the most scientifically valid method of evaluating standard treatments against the risks and benefits of medical innovations. Clinical research becomes more rewarding as neurosurgeons gain familiarity with the particulars of the structure and relevance of expertly designed clinical cooperative trials. The basic principles and the significance of biometrical essentials (research hypothesis, comparability, randomized and non-randomized trials, phases of studies and planning steps) are briefly discussed. A guide to the pertinent literature is provided. PMID- 1882711 TI - The effect of detergents on firefly luciferase reactions. AB - The reaction rate of ATP-limited firefly luciferase-catalysed reactions, is affected by the presence of detergents. Anionic detergents inhibit luciferase activity without causing significant enzyme inactivation during the reaction. Cationic detergents increase reaction rate several-fold with a sharply defined optimum concentration of detergent for the effect. However, cationic detergents inactivate firefly luciferase during the reaction, resulting in a continuously decreasing reaction rate. Under such conditions, peak light intensity must be used as an indication of initial reaction rate. The inactivation rate increases with increasing detergent concentration. Non-ionic and zwitterionic detergents increase reaction rate over a broad range of detergent concentrations. Enzyme stability during the reaction is not affected by non-ionic detergents and only affected by zwitterionic detergents at high detergent concentration. Cyclodextrins, which can increase reaction rates of some chemiluminescent reactions, have little effect on firefly luciferase activity. Assays for ATP using firefly luciferase must be internally standardized by the constant addition technique in which a known amount of ATP is added to the test sample, since external calibration of such assays, by reference to a previously prepared standard curve, can lead to imprecision when detergents are present. PMID- 1882713 TI - Value of electroencephalogram in prediction and diagnosis of vasospasm after intracranial aneurysm rupture. AB - The Electroencephalogram (EEG) of 151 patients whose ruptured aneurysm was confirmed by CT scan and angiography was recorded on the first day (D1) and the fifth day (D5). On D1, EEG had a prognostic value: among 46 patients with normal EEG, 72% presented neither further electrical ischaemic features nor delayed angiographic vasospasm; on the other hand, when bilateral bursts of slow waves, "axial bursts" or slow delta waves were recorded (78 cases), 97% exhibited EEG signs of ischaemia and angiographic vasospasm a few days later. These data were clearly related to the importance of the haemorrhage, specially when thick clots in the subarachnoid cisterns were found on the CT scan. On D5, EEG had a diagnostic value: focal or asymetrical bilateral delta waves occurring at that date seemed to correspond to ischaemia; among 107 patients with these electrical features, an angiographic vasospasm appeared in 96% of cases, and the importance of electrical abnormalities could be related to the degree of arterial narrowing. We conclude that EEG data are very useful in prediction as well in recognition of post-subarachnoid haemorrhage ischaemia due to vasospasm and are sufficiently precise to postpone control angiography and operation, when delayed surgery is programmed. PMID- 1882714 TI - Medical and surgical treatment of intracerebellar haematomas. AB - 15 cases of intracerebellar haematomas [11 spontaneous, 2 traumatic and 2 unclear] were presented. Hypertension was thought to be a main risk factor in 91% in 11 of the spontaneous cases. 11 cases were treated medically. They were usually conscious, scoring not less than 13 in GCS with subacute or chronic picture of illness and harbouring small haematomas below 3 cm in diameter situated almost always in the hemisphere and with no signs of ventricular dilation. Mortality in medically treated patients was 9% [1 case]. The remainder were discharged in good state, usually with no or only slight neurological deficit. Complete haematoma absorption took about 14 days. There were no signs of delayed hydrocephalus in subsequent CT scans. When the haematoma was large, more than 3 cm in diameter, located usually in the vermis or in the vermis and cerebellar hemisphere, sometimes with ventricular involvement, the clinical presentation was acute and required CT diagnosis and surgical evacuation without delay due to low and deteriorating conscious level. Postoperative mortality was 25%, but delayed mortality was 100%. Vertebral angiography was performed in all cases of spontaneous haemorrhage and was normal in 54%, revealed atheromatous changes in 36% and the signs of cerebellar haematoma in only 10%. Arteriovenous malformations were excluded from this study. The authors believe, that the benign course of intracerebellar haematomas is more frequent than it was considered previously and needs no surgical treatment in many cases. PMID- 1882715 TI - Bilateral epidural haematoma. AB - Bilateral acute epidural haematoma are found in 2-10% cases. They are associated with high mortality. We have analysed twenty cases of bilateral epidural haematoma found over a period of eleven years. In 60% cases haematoma was across the midline and in 40% cases haematoma was found at different locations on either side. Skull fracture was present in 95% cases. Mortality in our series was 20%. PMID- 1882716 TI - Craniofacial resection for anterior skull base tumours. AB - This study presents a series of 10 patients with anterior skull base tumours, treated by a team of neurosurgeons and head- and neck surgeons. The series included 7 malignant tumours of the nose and paranasal sinuses and 1 retinoblastoma, all with intracranial extension through the lamina cribrosa. There were also 2 patients with an anterior base meningioma, growing into the ethmoid sinus and the nasal cavity. 8 tumours were resected by a combined bifrontal craniotomy and uni- or bilateral rhinotomy. In 2 cases a bifrontal craniotomy alone without facial incision sufficed. The skull base was closed with a pediculated pericranial flap and a split-thickness free skin graft underneath. There were no postoperative problems of wound infection, CSF-leakage or meningitis. Recurrent tumour growth or systemic metastasis occurred in 5 out of 7 patients with malignant tumours, 6 months to 2 years postoperatively. The related literature and especially questions of operative indications and technique, including different possibilities of closure and reconstruction of the skull base, are discussed. PMID- 1882717 TI - Correlations of female steroid hormone receptors with histologic features in meningiomas. AB - A series of 39 samples were obtained from meningiomas in 28 patients in order to investigate the relationships of the oestrogen receptor (OER) and progesterone receptor (PR) with the tumoural subtype and some histological features. Twenty one samples were positive (greater than 10 fmole/mg protein), 7 were OER-PR negative, and 1 was positive in both receptors. Twenty-two samples were considered as syncitial, 7 transitional, 7 fibroblastic and 3 angioblastic. The histological subtype was not found to be significantly related to the presence or absence of PR. Relations were not observed between the progestin receptor and the following histological parameters: cellular pattern, cell density, nuclear polymorphism, mitosis, lymphoplasmacellular infiltrates, degree of vascularization, psammoma bodies and interstitial fibrosis. Only the presence of intratumoural necrosis was significantly related with a low PR levels. However, progesterone binding activity was lower in tumours with numerous psammomas, fibroblastic cell pattern and interstitial fibrosis. The clinical and biological significance of these results is discussed. PMID- 1882718 TI - Posttraumatic ulnar neuropathy versus non-traumatic cubital tunnel syndrome: clinical features and response to surgery. AB - The outcome of 53 patients operated on either for posttraumatic ulnar neuropathy (PUN) or non-traumatic cubital tunnel syndrome (CTS) was reviewed after 3 years follow-up. Results were analyzed and compared considering the surgical technique used (neurolysis versus anterior transposition or combined) and a variety of clinical features that could influence outcome after nerve release. In the whole series, excellent outcome was obtained in 39 patients (73%). No major differences were found with the different surgical procedures. Slightly better results, but no statistically significant, were found in cases with CTS. As to clinical parameters, patients with CTS had a higher mean age, a shorter duration of symptoms and most were men. The presence of symptoms for more than one year before operation significantly diminished the chance of satisfactory recovery in cases with CTS, but not in those with PUN. For both CTS- and PUN-cases with symptoms for more than one year, neurolysis plus anterior transposition was the more useful technique. Our study shows that CTS and PUN differ to a certain extent in their clinical profile, electrophysiological findings and response to different surgical approaches and hence can be considered as two different clinical entities. PMID- 1882719 TI - Commercial external ventricular drainage sets: unsolved safety and handling problems. AB - Twelve commercially available sets for drainage of cerebrospinal fluid were tested for handling, design, features for fixation of the ventricular catheter, reliability of the anti-reflux valve, obstruction, efficiency of the air ventilation filter caps, accuracy of flow measurement and adjustment of flow, quality of material, adjustment, and cost. All systems showed considerable deficiencies in their reliability and handling. None of them can be recommended without certain restrictions and they should all be revised. PMID- 1882720 TI - Neurosurgical intensive care improves outcome after severe head injury. AB - The present study compares the clinical outcome, as expressed by the Glasgow outcome scale, of two groups of severely head injured patients treated before (49 patients) and after (72 patients) the establishment of a neurosurgical intensive care (NIC) unit at the department of neurosurgery. Uppsala University Hospital. The number of "good recoveries" increased significantly after the establishment of the NIC. This was confirmed by univariate analysis (p less than 0.05) and by multivariate analysis using the logistic regression model to adjust for differences between the two groups of patients (p less than 0.05, p less than 0.005). The most striking improvement was found in patients with a Glasgow coma motor score (GCSM) greater than or equal to 4 on admission. In this subgroup of patients the "good recoveries" increased from 15% to 52%. The object of NIC is basically to prevent or minimize secondary brain damage, and it seems logical that the effect of such care is most obvious in GCS M greater than or equal to 4 patients in whom a good outcome can be anticipated if secondary damage can be prevented or minimized. In conclusion, the present study shows that improved clinical outcome after severe head injury can be achieved by organizing an NIC unit with a well trained staff capable of providing this care 24 hours a day using established methods of surveillance and treatment. PMID- 1882721 TI - Classification of supratentorial arteriovenous malformations. A score system for evaluation of operability and surgical strategy based on an analysis of 66 cases. AB - A classification of arteriovenous malformations (AVM) is proposed, which is based on a retrospective analysis of the records and results of radical operation in 57 patients between 1983 and 1990. It represents the new developments and more recent technical facilities which influence operability of supratentorial AVMs. Predictability of outcome has been settled upon three groups of factors: anatomical, haemodynamical, and clinical. Anatomical factors are localisation and sectorisation of AVM, determination, caliber and straightening of feeding arteries. Haemodynamical factors are volume of AVM and vascular autoregulation, circulatory velocity of red blood cells in the main arteries of the neck and brain tissue cellular steal. Clinical factors are age, previous rupture of AVM, associated diseases and malformations of vital organs. Each of these factor groups has been divided into parameters to which a code number from 0 to 5 according to the severity of the considered parameter has been attributed. When a contraindication for radical surgery was clearly obvious, as, for example, an AVM with extension to the upper brain stem, number 10 was given. This grading has been done by a team of four persons (3 neurosurgeons including the senior author, and one biophysicist). By adding up all code numbers an Operability Score for a given patient is defined by the number of points, with a minimum of 3 and a maximum of 69. In cases with a score higher than 30 surgery is not advisable. A score between 21 and 30 indicates that always several staged operations are required, whilst only some of the patients with a score between 11 and 20 may require two stage operative treatment. The AVM in patients with a score under 10 can always be radically excised in a single stage operation. We have been able to demonstrate that the Operability Score allows a reliable prediction of outcome, thus giving indications and contraindications for surgery, and also for the surgical strategy. Moreover, we have explained why surgery had been refused in 9 additional cases during the same period. The causes of 8 fatalities out of 57 surgical cases are analyzed. These 57 cases represent a systematically explored series of the senior author; his experience is based upon 295 personal AVM cases (1958-1990). PMID- 1882722 TI - A comparative study of the Reaction Level Scale (RLS85) with Glasgow Coma Scale (GCS) and Edinburgh-2 Coma Scale (modified) (E2CS(M)). AB - In this work a new coma scale for the assessment of responsiveness in acute brain disorders, constructed near the year 1985 by Scandinavian investigators, the Reaction Level Scale (RLS85), is compared with two other coma scales namely: (i) the Glasgow Coma Scale: (GCS); (ii) the Edinburgh-2 Coma Scale, after modification: (E2CS(M)). The study proceeded in the form of a statistical analysis of assessments made on 46 patients according to RLS85 and GCS (i.e., when comparison was with GCS) and on 28 patients according to RLS85 and E2CS(M). In all 74 cases two physicians participating as "observers" carried out the assessments. They were both contacting the patient--not together but- successively within a time interval of less than 20'. Hence the data appeared as "pairwise" observations for any of the three scales above. The results of the analysis, arising from a rather strict statistical reasoning, can be summarized as follows: (1) The rank correlation coefficient r(s) between: (i) RLS85 and GCS sum score, (ii) RLS85 and E2CS(M), was found to be at a satisfactory level meaning that all three scales indicate almost the same "ranking order of severity". (2) Reliability was compared by taking into account as to what extent the two observers agreed on RLS85 and--simultaneously--disagreed on the other scale. The "sign" test was applied and as a result RLS85 proved to be more reliable than; (i) GCS (EMY profile), (ii) GCS sum score, and (iii) E2CS(M), in all the above mentioned at a high level of significance. (3) Apart from the test above, some values of the index kappa (kappa) of interobserver agreement were calculated. Those corresponding to RLS85 are considerably higher. In particular the overall value based on 74 pairwise assessments amounted to kappa = 0.733 associated with a standard error sigma(kappa) = 0.061. This was a satisfactory result regarding the features of RLS85. (4) As far as coverage is concerned, again--by the "sign" test--the predominance of RLS85 versus GCS (EMY profile) was accepted. PMID- 1882723 TI - Rapid determination of thalamic CT-stereotactic coordinates: a method. AB - The anterior and posterior commissures (AC; PC) are the most frequently used reference points for target determination in functional stereotactic surgery. Computerized tomography (CT) has been slow in replacing ventriculography for identification of these points, primarily because in most methods described to date, the AC/PC plane had to be identified by reformatted CT images or cumbersome mapping procedures. The authors describe their methodology for determination of functional CT-stereotactic coordinates using the Brown-Robert-Wells (BRW) stereotactic system, axial CT imaging, and a proportional method to rapidly scale standard stereotactic map coordinates to the diencephalic size of any individual patient. 1. CT gantry angulation coinciding with Twining's line allows rapid identification of the AC/PC plane on axial CT. 2. Determination of the AC/PC distance with the "measure distance" function of the scanner enables the surgeon to rapidly find the proportional coordinates for either V.O.P., V.im., or V.C. 3. This localization method takes little more time than a routine stereotactic biopsy. Its application is easy, demanding only a few minutes of CT-console time, employing the standard computer software available in every current CT scanner. The method was been successfully employed in 25 functional thalamic procedures. PMID- 1882724 TI - Pathogenesis and treatment of delayed post-traumatic syringomyelia. AB - The role of trauma in the pathogenesis of syringomyelia has been known for a long time. Repeated microtraumata have been considered to play a role in triggering the classical syringomyelia on the basis of a congenital predisposition. It has been proven that post-traumatic arachnoiditis can cause cavitation in the spinal cord and probably syringomyelia stricto sensu as well. The delayed appearance of syringomyelia after a severe single spinal trauma resulting in contusion of the spinal cord without the complication of arachnoiditis is a more recent issue, but is now well-known. Delayed syringomyelia after a minor single spinal trauma, with at first complete recovery, is extremely rare, and is probably often disregarded as a diagnosis. Having studied such a case, with complete neuroradiological work up, we want to draw attention to the pathogenetic aspects and the possibilities for treatment, of which the syringoperitoneal shunt seems to be the most efficient one. PMID- 1882725 TI - Sturge-Weber-Dimitri disease? In association with an astrocytoma. AB - A patient with parieto-occipital cortical calcification characteristic of Sturge Weber-Dimitri disease (SWDD) is of interest in that she lacked the facial portwine lesion and almost all other features of the disease. She subsequently developed an astrocytoma in the underlying white matter. Although the absence of the facial lesion in SWDD has previously been described, there has been no report of a glioma developing in such a patient. The association of SWDD and astrocytoma in this case most likely has been fortuitous. PMID- 1882726 TI - Inositol metabolism in yeasts. AB - Because of its accessibility to genetic and molecular studies, Sacch. cerevisiae is an attractive organism in which to pursue studies of the complex roles of phosphoinositides and other inositol-containing metabolites. Biochemical studies have clearly demonstrated that PI, PIP, PIP2 and the inositol phosphates derived from them exist in Sacch. cerevisiae. It is clear that they are synthesized and turned over following pathways similar to those described in higher eukaryotes. Recent studies on yeast have also suggested that inositol phospholipids may play roles in complex signalling pathways similar to those detected in animal cells. In addition, inositol has been demonstrated to function in yeast as a global regulator of phospholipid synthesis. This regulation occurs on a transcriptional level and is highly complex. It is not yet known whether similar inositol mediated regulation of phospholipid synthesis occurs in other eukaryotes. PMID- 1882727 TI - The bacterial flagellum and flagellar motor: structure, assembly and function. AB - The bacterial flagellum is a complex multicomponent structure which serves as the propulsive organelle for many species of bacteria. Rotation of the helical flagellar filament, driven by a proton-powered motor embedded in the cell wall, enables the flagellum to function as a screw propeller. It seems likely that almost all of the genes required for flagellar formation and function have been identified. Continuing analysis of the portions of the genome containing these genes may reveal the existence of a few more. Transcription of the flagellar genes is under the control of the products of a single operon, and so these genes constitute a regulon. Other controls, both transcriptional and post transcriptional, have been identified. Many of these genes have been sequenced, and the information obtained will aid in the design of experiments to clarify the various regulatory mechanisms of the flagellar regulon. The flagellum is composed of several substructures. The long helical filament is connected via the flexible hook to the complex basal body which is located in the cell wall. The filament is composed of many copies of a single protein, and can adopt a number of distinct helical forms. Structural analyses of the filament are adding to our understanding of this dynamic polymer. The component proteins of the hook and filament have all been identified. Continuing studies on the structure of the basal body have revealed the presence of several hitherto unknown basal-body proteins, whose identities and functions have yet to be elucidated. The proteins essential for energizing the motor, the Mot and switch proteins, are thought to exist as multisubunit complexes peripheral to the basal body. These complexes have yet to be identified biochemically or morphologically. Not surprisingly, flagellar assembly is a complex process, occurring in several stages. Assembly occurs in a proximal-to-distal fashion; the basal body is assembled before the hook, and the hook before the filament. This pattern is also maintained within the filament, with monomers added at the distal end of the polymer; the same is presumably true of the other axial components. An exception to this general pattern is assembly of the Mot proteins into the motor, which appears to be possible at any time during flagellar assembly. With the identification of the genes encoding many of the flagellar proteins, the roles of these proteins in assembly is understood, but the function of a number of gene products in flagellar formation remains unknown.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1882728 TI - Mechanical behaviour of bacterial cell walls. PMID- 1882729 TI - The physiological activity of bacteria attached to solid surfaces. PMID- 1882730 TI - Organic acids: chemistry, antibacterial activity and practical applications. PMID- 1882731 TI - Development of the first fellowship training program in neuroradiology in North America. PMID- 1882732 TI - Is there a scientist in the house? An endangered species: the neuroradiologist as clinician-investigator. PMID- 1882733 TI - Angiography in patients with occlusive cerebrovascular disease: views of a stroke neurologist and neuroradiologist. PMID- 1882734 TI - Hyperglycemia augments ischemic brain injury: in vivo MR imaging/spectroscopic study with nicardipine in cats with occluded middle cerebral arteries. AB - Hyperglycemia is often associated with an increased frequency of cerebrovascular disease and exacerbation of neuronal injury in focal ischemic cerebral infarction. We used a combination of high-field proton MR imaging and 1H and 31P MR spectroscopy to investigate whether hyperglycemia would adversely influence cerebral metabolism and eventual infarct size following unilateral occlusion of the middle cerebral artery (MCA) of cats pretreated with the calcium channel blocker nicardipine. Normoglycemic animals injected with 10 micrograms/kg of nicardipine (8 micrograms.kg-1.hr-1 maintenance dose) manifested only mild disturbances in phosphorus metabolism and cerebral pH regulation compared with untreated controls, and showed a significant reduction in infarct size 7 hr after MCA occlusion. By comparison, hyperglycemic cats (plasma glucose, 200-300 mg/dl) had significantly reduced cerebral high-energy phosphates, elevated lactic acid, and larger ischemic lesions in the occluded MCA territory, irrespective of whether they were treated with nicardipine. These results indicate that moderate hyperglycemia can exaggerate ischemic brain damage by enhancing formation of tissue lactic acid and impairing normal phosphorus metabolism. One implication of this study is that dextrose should not be provided to patients with acute ischemic stroke. PMID- 1882735 TI - Cerebral ischemia: evaluation with contrast-enhanced MR imaging. AB - Eighty patients with a total of 82 ischemic lesions were examined with contrast enhanced MR imaging 1 hr to 1 month after onset of symptoms. The studies were reviewed retrospectively to determine the presence of arterial enhancement and the patterns of parenchymal enhancement. Arterial enhancement was often detected on the initial MR examination (45%), was frequently demonstrated in cortical infarction (86%), in some cases preceded the development of signal changes on T2 weighted images, and resolved by 11 days. The presence of arterial enhancement appeared to be a better indicator of clinical severity than was the presence of proximal vessel occlusion on MR or angiographic studies. Two patterns of parenchymal enhancement were seen: progressive enhancement and early and/or intense enhancement. In patients with the progressive pattern, parenchymal enhancement on postcontrast T1-weighted images was rarely seen before 7 days, while signal abnormalities on T2-weighted images were intense during the first few days. The early and/or intense enhancement pattern was usually present within the first 3 days, approximated or exceeded the area and intensity of signal changes on T2-weighted images, and was usually associated with minimal or reversible neurologic sequelae (except when located in or near a watershed zone), suggesting a lesser degree of ischemic insult than was associated with the progressive pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882736 TI - Dilated intercavernous sinuses: an MR sign of carotid-cavernous and carotid-dural fistulas. AB - Dilated venous channels traversing the sella and connecting the two cavernous sinuses were seen on contrast-enhanced MR images in four patients with angiographically proved carotid fistulas. The anatomy and variations of these so called intercavernous sinuses are discussed and are demonstrated in Latex injected anatomic specimens. Direct visualization of the intercavernous sinuses on contrast-enhanced MR images may serve as an ancillary sign for the diagnosis of carotid-cavernous or carotid-dural fistulas near the sella. PMID- 1882737 TI - Physiologic mechanisms underlying the delayed delta sign. AB - The negative or empty delta sign is considered to be nearly pathognomonic of superior sagittal sinus thrombosis on contrast-enhanced CT scans. We describe a visually similar sign, seen in five (10%) of 50 patients who had delayed cranial CT scans performed at intervals greater than 30 min after injection of contrast material. This new sign (which we call the delayed delta sign) closely mimics the classic negative delta sign and may thus represent a potential visual pitfall leading to an erroneous diagnosis of sagittal sinus thrombosis if only postcontrast images are viewed. The physiologic mechanisms underlying the appearance of the delayed delta sign are discussed. PMID- 1882738 TI - MR imaging of reversible cyclosporin A-induced neurotoxicity. AB - Neurotoxicity is a recognized complication of cyclosporin A (CsA) therapy in patients undergoing organ transplantation. It is most commonly manifested by fever, seizures, and altered mental status. Cortical blindness and speech and motor disturbances can also occur. Changes seen in cerebral white matter on imaging studies are nonenhancing areas of hypoattenuation on CT and T2 prolongation on MR. We report three cases of CsA-induced neurotoxicity in which reversible changes were observed in the cerebral white matter. In the first patient, CsA neurotoxicity occurred 1 week following orthotopic liver transplantation. In the second patient, CsA neurotoxicity coincided with an episode of severe systemic hypertension 4 weeks after cardiac transplantation. The third patient experienced seizures 1 month after heart/lung transplantation for cystic fibrosis. A current theory postulates a relationship between diminished serum cholesterol and CsA neurotoxicity. This theory, however, does not satisfactorily address all cases of CsA neurotoxicity. In particular, serum cholesterol measurements were normal in cases 2 and 3 and probably were normal in case 1, despite diminished cholesterol levels preoperatively. Although the matter of CsA-induced neurotoxicity remains unresolved, we suggest that endothelin, a newly described neuropeptide that causes intense vasoconstriction and that has been implicated in cerebral vasospasm, may potentiate CsA-induced damage to endothelium and promote CsA neurotoxicity. PMID- 1882739 TI - Reduced hypothalamic blood flow after radiation treatment of nasopharyngeal cancer: SPECT studies in 34 patients. AB - To determine the effect of cranial irradiation on hypothalamic blood flow, we performed 44 regional cerebral blood flow studies with 99mTc hexamethyl propyleneamine oxime (HMPAO) single-photon emission CT (SPECT) on four normal volunteers and 34 patients with pathologically proved nasopharyngeal cancer. Twenty-three men and 15 women, 30-65 years old, were divided into four study groups: group 1 served as a control and consisted of four normal volunteers and six patients studied prior to cranial irradiation; group 2 patients had cranial irradiation half a year before the SPECT study (n = 12, one from group 1); group 3 patients were irradiated 1 year before the study (n = 13, three from group 1 and two from group 2); and group 4 patients were irradiated at least 5 years before SPECT imaging (n = 9). Six patients were studied twice. Quantification of the 99mTc-HMPAO brain SPECT studies was done separately by three radiologists to obtain the hypothalamus/occipital (H/O) and hypothalamus/parasagittal (H/P) ratios. Endocrinologic studies were performed in all cases and the hypothalamus thyrotroph-thyroid, hypothalamus-gonadotroph-testis (ovary), hypothalamus lactotroph, hypothalamus-somatotroph, and hypothalamus-corticotroph-adrenal axes were evaluated separately. We determined that regional hypothalamic blood flow was reduced after cranial irradiation in patients with nasopharyngeal cancer. The H/O ratio of groups 3 and 4 did not differ from that of group 2 (one-half year after cranial irradiation). The H/O ratio was significantly reduced 6 months and 1 year after cranial irradiation; mean +/- SD = 0.5801 +/- 0.0829 (p less than .025), 0.5725 +/- 0.0791 (p less than .01) versus 0.6477 +/- 0.0458 before cranial irradiation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882740 TI - Generalized seizure after i.v. administration of gadopentetate dimeglumine. PMID- 1882741 TI - Flow-sensitive MR imaging of ventriculoperitoneal shunts: in vitro findings, clinical applications, and pitfalls. AB - To determine ventriculoperitoneal shunt patency during routine MR imaging of the head, 23 patients were studied with T1-weighted fast-field-echo scans. Without knowledge of the results of previous MR/CT studies or of the patients' clinical history, we reviewed the fast-field-echo studies and divided them according to those judged to have shunt flow (18) and those judged not to have flow (five). Fast-field-echo sequences showed high signal intensity, consistent with CSF flow and shunt patency in 17 medium-pressure systems and one high-pressure system. No signal was seen in five patients with high-pressure valve shunts. Combined clinical evaluation and MR/CT studies showed that three patients had probable shunt malfunction. One patient had true shunt malfunction; and although malfunction was thought to be present in two symptomatic patients, surgical revision showed the shunts to be patent. The possibility of temporary shunt obstruction is postulated to explain the clinical and MR findings in those two cases. The remaining two cases (9% of the patients) had no clinical evidence of shunt malfunction, and the MR findings probably reflected periodic CSF flow. One patient had an intracranial segment that was not connected and showed no flow on MR. No false-positive results (apparent flow in a nonfunctioning shunt) occurred. Using a standard medium-pressure shunt system, we constructed and imaged a phantom, which confirmed our clinical observations. T1-weighted fast-field-echo sequences may be useful in assessing patency of medium-pressure CSF shunt systems. PMID- 1882742 TI - Flow-sensitive MR imaging of ventriculoperitoneal shunts: in vitro findings, clinical applications, and pitfalls. PMID- 1882743 TI - Optimizing brain MR imaging protocols with gadopentetate dimeglumine: enhancement of intracranial lesions on spin-density- and T2-weighted images. AB - To determine whether long TR MR imaging is best performed before or after IV administration of gadopentetate dimeglumine, we obtained spin-density- and T2 weighted images before and after contrast administration in 21 patients with known intracranial enhancing lesions. Of 25 lesions demonstrating enhancement on T1-weighted sequences, 21 showed mild or moderate enhancement on spin-density weighted sequences and 20 showed mild enhancement on T2-weighted sequences. Importantly, no spin-density or T2 information was obscured by the administration of gadopentetate dimeglumine, and no T2 shortening effects were visible. Two new foci of enhancement were visible on postcontrast spin-density- and T2-weighted images that were missed on postcontrast T1-weighted images and on precontrast spin-density- and T2-weighted studies. Visualization of new areas of enhancement is the main advantage provided by the long TR images obtained after IV injection of gadopentetate dimeglumine. The most likely reason for the appearance of these newly visualized lesions is thought to be delayed enhancement. This imaging protocol also allows the display of adjacent edema or gliosis and enhancing lesions on a single image. Additionally, in three cases, posterior fossa phase shift artifacts raised the suspicion of an enhancing lesion on postcontrast T1 weighted images, but the cerebellum was shown to be normal on the postcontrast spin-density- and T2-weighted studies. On the basis of our results, we recommend obtaining long TR images after rather than before the administration of gadopentetate dimeglumine in patients with intracranial enhancing lesions. PMID- 1882744 TI - Composite addition technique: a new method in CT scanning of the posterior fossa. PMID- 1882746 TI - MR imaging of incomplete band heterotopia. PMID- 1882745 TI - Neurocutaneous melanosis and temporal lobe tumor in a child: MR study. PMID- 1882747 TI - Hemolytic uremic syndrome: MR findings of CNS complications. PMID- 1882748 TI - MR imaging of an extreme case of cerebellar ectopia in a patient with Chiari II malformation. PMID- 1882749 TI - MR imaging of primary trochlear nerve neoplasms. AB - We present the clinical, anatomic, and MR imaging findings in six patients with seven primary trochlear nerve neoplasms, as well as the MR and clinical criteria that serve to establish the diagnosis of these rare cranial nerve neoplasms. Three patients had a history of neurofibromatosis and five patients had clinical evidence of a trochlear nerve palsy. Six of seven neoplasms produced localized, fusiform enlargement of the proximal cisternal segments of the trochlear nerves. The lesions that were visible on noncontrast MR scans (T1-, T2-, and proton density-weighted) had signal intensities that were virtually identical to normal brain parenchyma. All lesions showed intense, homogeneous enhancement on contrast enhanced scans. Contrast-enhanced imaging was necessary for the detection of five of seven lesions and greatly increased the value of the MR study in all six patients. PMID- 1882750 TI - MR appearance of intraorbital granular cell tumor: a case report. PMID- 1882751 TI - Orbital varices: a new technique for noninvasive diagnosis. PMID- 1882752 TI - Middle ear cholesteatoma extending into the petrous apex: evaluation by CT and MR imaging. AB - CT and MR imaging findings were reviewed in four cases of acquired cholesteatoma of the middle ear that extended medially into the petrous apex and middle cranial fossa. In one case the lesion further extended anteromedially into the sphenoid sinus. CT demonstrated the lesions as nonenhancing hypodense masses with bone destruction, extending medially from the middle ear cavity to the petrous apex region. On MR imaging, the lesion was slightly hypointense relative to brain on T1-weighted images and hyperintense on T2-weighted images. MR imaging clearly delineated the extraaxial location of the lesion and associated brain displacement. The medial extension of the cholesteatomas seems to have proceeded via a detour around the bony labyrinth into the petrous apex region by following normal pathways of temporal bone pneumatization. PMID- 1882753 TI - Nasopharyngeal and temporal bone blastomycosis: CT and MR findings. PMID- 1882754 TI - Spontaneous drainage of an ethmoidal mucocele: a possible cause of pneumosinus dilatans. PMID- 1882755 TI - Ventriculus terminalis of the conus medullaris: MR imaging in four patients with congenital dilatation. AB - MR findings in four patients with MR evidence of congenital cystic dilatation of the ventriculus terminalis were reviewed retrospectively. The ventriculus terminalis is a small cavity of the conus medullaris that forms during embryonic development as result of canalization and retrogressive differentiation. The dilated ventriculus terminalis appears on MR images as a small ovoid cavity with regular margination; intralesional fluid resembles cerebrospinal fluid on all MR sequences. After injection of contrast material, MR imaging shows no enhancement of the cyst or its wall, and thus differentiates congenital dilatation of the ventriculus terminalis from cystic tumors, which occur more frequently in this region. PMID- 1882756 TI - Venous infarction of the spinal cord resulting from dural arteriovenous fistula: MR imaging findings. AB - Three patients with spinal dural arteriovenous fistula presented with acute and/or progressive myelopathy. The thoracic cord was focally enlarged and poorly defined on MR images in two of the patients. One individual showed focal cord atrophy, and one demonstrated abnormal intrathecal vessels. In all patients MR studies revealed cord enhancement after IV administration of gadopentetate dimeglumine. The MR findings are believed to represent disruption of the blood cord barrier associated with cord ischemia and/or infarction, which, in turn, is caused by venous stasis resulting from the fistula. The diagnosis in each case was confirmed by the combined results of myelography, spinal arteriography, and surgery. Surgical excision or embolization of the fistula produced a poor return of lost function but an arrest in the progression of paresis. One of the patients had constant severe back and leg pain postoperatively, and a follow-up MR study 5 months after surgery showed focal atrophy and persistent enhancement of the thoracic cord. The patient with preoperative focal cord atrophy had an MR examination 1 year prior to surgery, which revealed enhancement of the cord similar to that seen on the immediate preoperative MR study. This patient also had severe pain in the back and lower extremities preoperatively, which accompanied her progressive paraparesis. It is believed that long-standing enhancement of the spinal cord in patients with dural arteriovenous fistula probably results from chronic progressive venous ischemia, which may be irreversible and cause pain of a central type. PMID- 1882758 TI - Technical note. Device to facilitate MR imaging of patients in skeletal traction. PMID- 1882757 TI - Spinal epidural angiolipoma: MR findings. PMID- 1882759 TI - Intracerebral gangliogliomas in patients with partial complex seizures: CT and MR imaging findings. AB - The clinical and radiologic findings in 19 patients with partial complex seizures and surgically proved intracerebral gangliogliomas were reviewed to characterize the radiologic features of these lesions. The CT and MR findings were not specific. On CT the gangliogliomas can be hypodense with no enhancement and they often have calcifications. On MR these tumors have a wide variety of signals. In five of our cases the tumor had a high-intensity signal with a cystlike component on proton density- and T2-weighted images. In five cases the lesion had an inhomogeneously intense signal on proton density-weighted images and high signal intensity on T2-weighted images. The tumor had high-intensity signal on both proton density- and T2-weighted images in four patients. Finally, in two cases the MR findings were normal. We recommend MR as the examination of choice for patients with partial complex seizures because it allows an artifact-free evaluation of the temporal region. However, CT should also be performed in order to recognize calcifications that may be missed on the MR examination. PMID- 1882760 TI - MR findings in extracerebral cavernous angiomas of the middle cranial fossa: report of two cases and review of the literature. PMID- 1882761 TI - Prominent dural enhancement adjacent to nonmeningiomatous malignant lesions on contrast-enhanced MR images. AB - Prominent dural enhancement was noted in 10 (16%) of 61 superficial malignant intracranial tumors studied with contrast-enhanced MR imaging during a 2-year period. Included were six glioblastomas, three parenchymal metastases, and one case of dural metastasis. Seven patients had surgery. In four, there was extensive leptomeningeal invasion in the center of the lesion. In two of these lesions there was firm attachment of the center of the tumor to the dura, but without dural invasion despite extensive external carotid artery supply to the tumor in one case. In two cases the overlying dura was normal, and there was no leptomeningeal tumoral invasion. In the case of dural metastasis, huge nodular lesions were present along the inner aspect of the dura. In none of the cases did prominent dural enhancement adjacent to the tumor correspond with tumoral invasion or extension to the dura. Prominent dural enhancement on contrast enhanced MR images appears to be much less frequent in malignant tumor than in meningioma, where it is seen in up to 60% of the cases. We believe this finding is more likely to represent reactive changes of the dura than tumoral invasion. PMID- 1882762 TI - Neurocytoma accompanied by intraventricular hemorrhage: case report and literature review. PMID- 1882763 TI - Unusual MR and CT appearance of an epidermoid tumor. PMID- 1882764 TI - Enhancement of pineal cysts on MR images. PMID- 1882765 TI - Embolization of arteriovenous malformations of the temporal lobe via the anterior choroidal artery. AB - The indications, technique, and results of embolization of arteriovenous malformations with liquid adhesive agents delivered through the anterior choroidal artery are reported. Arteriovenous malformations of the temporal lobe were found in four patients with intracerebral bleeding and two with intractable epilepsy. In five of the six, the dominant arterial feeder was the anterior choroidal artery. All patients underwent superselective catheterization of the anterior choroidal artery and embolization of the arteriovenous malformation. Complications related to the anterior choroidal artery embolization developed after embolization in one patient, after which we changed our technique of embolizing arteriovenous malformations via this artery. A thorough understanding of the functional anatomic structures supplied by each segment of the artery is important. Guidelines for safe catheterization and embolization are given. Embolization of arteriovenous malformations fed predominantly by the anterior choroidal artery is difficult and dangerous. An understanding of the functional anatomy of this artery and proper technique can enable successful embolization of arteriovenous malformations via this route. PMID- 1882766 TI - Cranial osteopetrosis: MR findings. PMID- 1882767 TI - Growing skull fracture simulating a rounded lytic calvarial lesion. PMID- 1882769 TI - Neurologic involvement in Behcet disease: imaging findings in 16 patients. AB - Behcet disease is a rare multisystem immune-related vasculitis that is prevalent in Japan, the Middle East, and many Mediterranean countries. In our study population of 36 patients with Behcet disease, 16 (44%) had CNS involvement. CT was noncontributory, except in a single patient with dural sinus thrombosis. MR imaging in nine patients showed foci of high signal intensity on T2-weighted images within the brainstem, the basal ganglia, and the cerebral hemispheres in that order of frequency. Unlike the plaques associated with multiple sclerosis, Behcet lesions show no predilection for the periventricular regions. PMID- 1882768 TI - Integrated MR imaging and proton nuclear magnetic resonance spectroscopy in a family with an X-linked spastic paraparesis. AB - Seven members of a family with an X-linked spastic paraparesis syndrome were analyzed by MR imaging and stimulated echo, solvent-suppressed proton nuclear magnetic resonance spectroscopy. The MR scans of three symptomatic males and two asymptomatic females demonstrated abnormal signal in the supratentorial white matter. Each of these patients had a proton spectroscopic examination of a 2 X 2 X 2 cm voxel localized to the abnormal white matter of the centrum semiovale. The spectra demonstrated depression of N-acetyl aspartate/creatine, N-acetyl aspartate/choline, and creatine/choline ratios compared with normal control subjects. Additionally, these patients had abnormal elevations of amino acid resonances in the 2.1-3.0 ppm range. In a patient with symmetric white matter signal intensity abnormalities, an asymmetric spectroscopic study correlated with asymmetric symptoms. One asymptomatic family member with a normal MR study had abnormal metabolite ratio measurements. She was referred for further evaluation, since the proton spectrum suggested she may possess the affected gene. If the findings in this study are duplicated in other cases of hereditary dysmyelinating syndromes, we believe the integrated MR/proton nuclear magnetic resonance spectroscopy examination will be of benefit in evaluating and counseling families with familial dysmyelinating disorders. PMID- 1882770 TI - Iohexol CT ventriculogram of multiple cerebral hydatid cysts. PMID- 1882772 TI - Intimal tears of the right atrium of the heart due to blunt force injuries to the abdomen. Its mechanism and implications. AB - We present six cases involving intimal tears of the right atrium of the heart. A proposed mechanism for this injury is discussed, along with implications of the lesion in fatally abused children and traumatized older patients who survive until hospitalization. PMID- 1882771 TI - Tuberous sclerosis: CT and MR findings. PMID- 1882773 TI - Firearms and adult, domestic homicides. The role of alcohol and the victim. AB - An epidemiological study was conducted to characterize adult, domestic homicides committed with firearms and to determine the role of alcohol intoxication in the likelihood of becoming a homicide victim. Data on 129 homicides in Ohio occurring between 1982 and 1985 were collected from police departments of major cities, the Ohio Department of Rehabilitation and Corrections, and county medical examiners. Forty-eight offenders were interviewed. Temporal and geographical patterns are discussed, as well as offender-victim relationships and the characteristics of the firearms used. High levels of blood alcohol in the victims suggest that alcohol is a risk factor for becoming a homicide victim, although data on alcohol consumption patterns in the population are necessary to advance this association. PMID- 1882774 TI - The moving, projected, annual total. A kinetic prognostic entity. AB - A simple, inexpensive method of prognostically calculating and graphically recording annual case loads of the various deaths investigated by today's medicolegal offices is presented. Graphic depiction of the numerical data provides a convenient way to compare current prognostications with the records of preceding years. PMID- 1882775 TI - Hyperthermia deaths in Finland in 1970-86. AB - All cases in which hyperthermia had been determined as the basic cause of death during the period 1970-86 were collected from the records of the Central Statistical Office of Finland. Of the total of 230 cases, 228 were included in the present study; the two remaining victims died abroad, and no autopsy was performed in Finland. Most of the hyperthermia deaths occurred while the decedent was taking a sauna bath; most decedents were men aged 42-62 years. An increase in the total number of hyperthermia deaths, and of male victims, was noted from the beginning of the 1970s onward; the number of female victims remained at a relatively steady level throughout, with the exception of a slight rise in 1986. Acute alcohol consumption was detected in most of the victims; in some cases there was also a reference to chronic alcoholism or recent long-term heavy drinking. The findings suggest that in addition to the acute hazardous effect of ethanol on thermoregulatory mechanisms, the long-term consumption of alcohol may have promoted fatal hyperthermia in these subjects. PMID- 1882776 TI - Mass deaths by gas or chemical poisoning. A historical perspective. AB - This review chronicles the characteristics of deliberate and accidental mass poisonings that occurred in World Wars I and II, in Bhopal, and in other historical cases up to and including modern wars. It also considers approaches to the investigation of such cases from the medicolegal as well as general standpoints. PMID- 1882777 TI - Use of facial approximation techniques in identification of Green River serial murder victims. AB - Since 1982, the remains of 41 victims of the Green River Serial Murderer have been recovered. The majority were discovered as skeletal remains, and 24 facial approximations have been used in attempts to develop leads for identification of nine of these victims. Nine different artists were used. Interpretations of the same victim varied greatly. For those victims subsequently identified, resemblance of the facial approximation to the deceased showed considerable variation, but in some cases was quite accurate. This experience created a unique opportunity to compare different methods of facial approximation techniques and artists, and to comment on their efficacy in aiding identification. PMID- 1882778 TI - Sudden unexpected death due to papillary fibroma of the aortic valve. Report of a case and review of the literature. AB - The case of the sudden unexpected death of a 21-year-old man due to embolization of segments of an aortic valve papillary fibroma to the left main and anterior descending coronary artery is presented. The literature regarding cardiac papillary fibroma is reviewed with particular reference to those cases associated with sudden death. PMID- 1882779 TI - Unusual blunt force wound patterns due to a hexagonal steel bar. AB - Pathologists routinely examine victims with blunt force traumatic injuries. Many of these victims exhibit injury patterns that can help identify the weapon used in the assault. Proper documentation that accurately portrays the injury pattern and allows for comparison with recovered weapons is therefore essential. Our office investigated a homicide with unusual blunt force injuries. This article presents the procedure that we followed to identify the weapon. PMID- 1882781 TI - Specimens for teaching forensic pathology, odontology, and anthropology. I. Soft tissue. AB - A set of specimens has been collected, preserved, and organized specifically for the teaching of forensic pathology, odontology, and anthropology. Plastination of soft tissue, whole organs, bones, and teeth has proven valuable in preserving delicate, friable, and calcined specimens. The dry, odorless, biologically inert specimens are durable and resistant to damage caused by handling. Subtle features of soft tissue pathology are well preserved. Patterned injuries change due to shrinkage, but remain easily recognizable. Plastinated whole jaws are still readily identifiable from antemortem records. Radiographic density is essentially unchanged. Putrid and charred specimens become quite manageable. PMID- 1882780 TI - Delayed cardiac rupture due to blunt chest trauma. AB - A 7-year-old boy fell from a 2.5-m height and suffered contusion of the thorax with hematoma in the soft tissues of the lateral chest wall. The rib cage itself remained intact. After 3 days, there was only local pressure sensitivity of the left hemithorax. On day 8 after the trauma, the child, who up to then had seemed to be in good health, suddenly died during lessons at school. Autopsy revealed a full-thickness rupture of the left ventricle with resultant cardiac tamponade. The macroscopic and histopathologic findings are presented and discussed. PMID- 1882782 TI - Specimens for teaching forensic pathology, odontology, and anthropology. II. Teeth and bone. AB - A set of specimens has been collected, preserved, and organized specifically for the teaching of forensic pathology, odontology, and anthropology. Plastination of soft tissue, whole organs, bones, and teeth has proven valuable in preserving delicate, friable, and calcined specimens. The dry, odorless, biologically inert specimens are durable and resistant to damage caused by handling. Subtle features of soft tissue pathology are well preserved. Patterned injuries change due to shrinkage, but remain easily recognizable. Plastinated whole jaws are still readily identifiable from antemortem records. Radiograph density is essentially unchanged. Putrid and charred specimens become quite manageable. PMID- 1882784 TI - Sudden, unexplained death in a Pacific Archipelago (Mariana Islands) PMID- 1882783 TI - Sexing of human clavicles using length and circumference measurements. AB - Measurement of clavicular length and circumference, and computation of clavicular robustness and length-circumference product from 724 autopsied adults of known age, sex, and body length between the ages of 15 and 96 years produced useful sex predictive values. This predominantly North American white population contained 560 males and 164 females with intact, nondeformed clavicles. Clavicle length and circumference and particularly their product have been found useful in sexing, but robustness as a single trait has not. Despite a significant overlap of male and female values, the use of single cutoff values allowed correct sex assignment of up to 93% of the entire study population, including 94% of males and 89% of females. The ratios of body length to clavicle circumference and to clavicle length are on average greater in women than in men. The former ratio yields male predictive values greater than 95% for those individuals with ratios falling below the cutoff value of 43, whereas the latter ratio is a relatively poor sex predictor. PMID- 1882785 TI - Identification of human remains lacking skull and teeth. A case report with some methodological considerations. AB - This report deals with a case in Denmark in which close cooperation among the local police, the Central Missing and Wanted Persons Search Squad, and the Institute of Forensic Medicine resulted in the positive identification of human remains (part of a skeleton), although the deceased's skull was missing, he had no teeth (but a dental prostheses), and an attempt at blood typing produced a false result. When the remains were found, there was no idea who the deceased might be. The initial forensic examination provided a general description (age, height, and sex), and reconstruction of the vertebral column showed extensive changes caused by arthrosis and changes typical for Scheurmann's disease. The description made on this basis was sent to police stations throughout the country and, far from where the remains were found, a police officer had received the report of a missing person who could have been the deceased. Further investigation was based mainly on the medical history of this missing person and the tracing of the effects found with the remains, and emphasized radiographic comparison. PMID- 1882786 TI - "Beaten to death". An autopsy series of homicidal blunt force injuries. AB - Although gunshot is by far the most common means of homicide in the United States, significant numbers of homicides are also perpetrated by other means. Blunt-force injuries are produced by a variety of objects, including hands and feet and many different weapons. Some of these objects produce distinctive patterns of injury of potential evidentiary value. This paper presents a series of 20 consecutive blunt-force homicides in adults. Seventy percent (14 cases) of the victims were men. Thirty percent (six cases) followed an argument or altercation. A number of the weapons used were "weapons of opportunity" seized in the course of the incidents. Sixty-nine percent (nine cases) of known assailants were acquainted with their victims. Few characteristic patterned injuries were seen. Not surprisingly, craniocerebral trauma was the most common cause of death. One half (10 cases) the victims survived their assaults for varying periods of time. Homicides due to blunt-force injury still pose a significant challenge for the forensic pathologist, who must obtain a complete and accurate history of the fatal incident, interpret patterns of injury and other findings at autopsy, and correlate all of the findings to make an accurate ruling of the cause and manner of death. PMID- 1882788 TI - What you should know about the methods, problems, interpretations, and uses of urea breath tests. PMID- 1882790 TI - Reproducibility of the rapid pull-through technique for categorizing lower esophageal sphincter pressure. AB - Duplicate measurements of basal lower esophageal sphincter (LES) pressure using a triple-lumen catheter and the rapid pull-through technique (RPT) were performed in 250 consecutive patients to determine their reproducibility for categorizing LES pressures as normal, hypertensive, or hypotensive. For all subjects, mean LES pressure did not differ for the two measurements (25.3 +/- 1.0 vs. 26.2 +/- 1.0 mm Hg, p greater than 0.5), but the correlation coefficient was only modest (r = 0.73). Reproducibility of categorization was 92% (230 of 250 subjects), and was best for subjects with normal (170/179, 95%) or hypotensive (24/26, 92%) values (for hypertensives: 36/45, 80%). Interstudy variability was least for the hypotensive group (1.8 +/- 0.2 mm Hg) and greatest for the hypertensive group (16.4 +/- 1.9 mm Hg). Likewise, the range of individual values from the triple lumen catheter was least for the hypotensive subjects (4.7 +/- 0.7 mm Hg) and greatest for those with hypertensive LES pressure (32.5 +/- 2.6 mm Hg). These data show that, despite its interstudy variability, the RPT reproducibly categorizes basal LES pressure in greater than 90% of cases. The technique appears least reliable in determining hypertensive LES pressure, where diaphragmatic contraction may most significantly contribute to measurement variability. PMID- 1882789 TI - Drug-induced esophagitis. AB - Drug-induced esophagitis is being recognized increasingly in the past few years. We have reviewed 175 cases with a view to classifying this disease based on pathology. Drug-induced esophageal injury tends to occur at the anatomical site of narrowing, with the middle third behind the left atrium predominating. The disease is classified broadly into two groups. The first group is transient and self-limiting, as exemplified by tetracycline- and emepronium-induced injury (57.3%). The second is the persistent esophagitis group, often with stricture with two distinct entities: 1) patients on nonsteroidal antiinflammatory agents whose injury is aggravated by gastroesophageal reflux (26.2%) (reflux aggravated), and 2) patients with potassium chloride and quinidine sulfate induced injury (16.2%) (persisting drug injury). We report a case that highlights the pathophysiology (delayed transit, persisting potassium within the stricture) of this type of injury which is not reflux aggravated. PMID- 1882787 TI - Occupational and industrial toxin exposures and the gastrointestinal tract. Gastrointestinal Toxicology Subcommittee of the American College of Gastroenterology Patient Care Committee. AB - The subcommittee on Gastrointestinal Toxicology of the Patient Care Committee of the American College of Gastroenterology has reviewed potential effects of exposures to occupational and industrial hazards on the gastrointestinal tract, liver and pancreas. This review is presented to 1) share clinical data concerning gastrointestinal toxicology, 2) emphasize the paucity of available information to the practicing clinician, and 3) stimulate basic research interest in this field. PMID- 1882791 TI - Which pH threshold is best in esophageal pH monitoring? AB - Two questions were examined, namely, 1) whether pH 4 is really the optimal threshold for the definition of acid gastroesophageal reflux, and 2) to what extent shifting of the upper limits of normal affects sensitivity and specificity of 24-h pH monitoring. To answer these questions, we studied 74 patients with proven reflux disease and 37 asymptomatic volunteers, using ambulatory 24-h esophageal pH monitoring. Gastroesophageal reflux was defined as episodes with esophageal pH of less than the threshold values 3.0, 3.5, 4.0, 4.5, or 5.0, respectively. For each of these pH thresholds, the percentage time with esophageal pH below the threshold was calculated separately for periods of upright and supine body position. Two-dimensional receiver-operating characteristic (ROC) analysis was used to define upper limits of normal. A maximum of sensitivity, specificity, and rate of correct decisions (all 89%) was obtained using pH 4 for the definition of gastroesophageal reflux, although other pH thresholds were not much worse. On the basis of pH 4, the upper limits of normal could be shifted around the "optimal upper limit of normal" within a certain limit without considerable loss of accuracy of pH monitoring. This may explain the divergences between upper limits of normal obtained by different laboratories. In conclusion, 1) the threshold pH 4 should further be used for the definition of acid gastroesophageal reflux, and, 2) within certain limits, shifting of the upper limits of normal has little effect on the accuracy of pH monitoring in gastroesophageal reflux disease. PMID- 1882792 TI - Basal and maximum acid output after continuous overnight gastric aspiration. AB - Basal and maximum acid outputs were measured on two occasions in a group of 15 duodenal ulcer (DU) patients in remission. The initial study was carried out after a nocturnal acid collection, whereas the second was carried out in the conventional manner without preceding nocturnal aspiration. No difference in the basal acid output, concentration, or volume of secretion was found between the two study days. Maximum acid output on the other hand, was significantly (p less than 0.02) reduced from 30.9 (14.2-41.2) mmol/h, median (+range), to 23.7 (8.1 33.7) mmol/h after overnight aspiration. The reduction in maximum acid output was attributable to a fall in the volume of gastric secretion from 280 (170-371) ml to 230 (142-280) ml. No fall in acid concentration was seen. We conclude that overnight gastric aspiration does not affect basal gastric secretion, but reduces the maximum acid output as a result of a reduced secretory volume. PMID- 1882793 TI - Helicobacter pylori-negative duodenal ulcer. AB - Most patients with chronic duodenal ulcer (DU) craters have gastritis associated with Helicobacter pylori (HP), now thought to be the major cause of DU. A smaller proportion of DU patients have no detectable HP. In this study, we examined the frequency and causes of HP-negative duodenal ulcers. In 302 consecutive patients with endoscopic diagnosis of duodenal ulcer, 284 (94%) were found to have associated HP gastritis, whereas 18 (6%) were HP-negative on histology, culture, and urease test. The largest subgroup of HP-negative patients (8/18) was made up of those who had been taking nonsteroidal antiinflammatory drugs (NSAIDs), followed closely (4/18) by patients with recent intake of antibiotics. Causes of DU in the remaining subgroups included two patients with duodenal Crohn's disease, two with Gastrospirillum hominis infection, one with penetrating carcinoma of the pancreas and one with no detectable cause. We conclude that, although the most common causal factor of duodenal ulcer is HP, some 6% of DU's will be HP-negative, signaling unusual etiology. It is now important to identify the cause of duodenal ulcer so as to initiate appropriate therapy. PMID- 1882794 TI - Simple noninvasive method to test efficacy of drugs in the eradication of Helicobacter pylori infection: the example of combined bismuth subsalicylate and nitrofurantoin. AB - Eradication of Helicobacter pylori infections has proved to be difficult. There is a need both for improved therapies and for ways to rapidly identify therapies that show sufficient promise to be worth pursuing. The objectives of this study were to evaluate the value of a therapeutic regimen of a bismuth salt plus nitrofurantoin for eradication of infection by H. pylori and to determine the validity/utility of the urea breath test in monitoring the progress of a clinical trial. We used an 80% eradication rule to define a promising therapeutic regimen, i.e., a regimen that eradicated the infection (no evidence of infection by H. pylori 4 wk after termination of therapy) in at least 80% of the individuals treated. Eighteen men (median age 38) with documented infection by H. pylori completed the study. At the end-of-study evaluation, H. pylori infection was eradicated (negative urea breath test, culture, and histology) in only one of 18 (5.5%) subjects; 15 were positive by the urea breath test, 16 by culture, 15 by Warthin-Starry stain, and 16 by the presence of acute-on-chronic inflammation. Using the 80% eradication rule, any one of these tests alone would have identified that the combination of antimicrobials tested was not effective in the eradication of the infection. We conclude that the urea breath test is a simple, noninvasive, cost-effective method to separate promising from unpromising candidate therapies and for the evaluation of new therapeutic concepts. PMID- 1882796 TI - Incidence of gallstones in liver cirrhosis. AB - We conducted a longitudinal follow-up of 72 patients with liver cirrhosis (LC) in order to assess gallstone (GS) incidence. The period of survey was 24.5 +/- 12.2 months. Patients were divided into two groups: group I--26 patients with ascites at the start or appearing during follow-up, and Group II--46 patients with compensated LC (no ascites) throughout the survey. During follow-up, 12 of 72 (16.6%) patients developed GS. The global cumulative incidence of GS was 5.5 cases/100 people/year. Age and sex had no influence on the incidence of GS in LC; neither had etiology or cirrhosis. On the contrary, the study revealed a significant increase in the incidence of GS in decompensated cirrhosis. In group I patients, GS appeared more frequently (34.6%) than in group II patients (6.5%) (chi 2 9.479; p less than 0.002). The cumulative incidence of GS was five times higher in decompensated versus compensated LC. PMID- 1882795 TI - Immunohistochemical expression of carbohydrate antigen 19-9 in gastric carcinoma. AB - Immunohistochemical localization for carbohydrate antigen 19-9 (CA19-9) was studied in the gastric tissues from 115 patients with advanced gastric carcinoma. We compared two groups: 57 patients who died of recurrence or metastases within 2 yr (group I) and 58 patients who survived 5 yr or more after resection (group II). The staining patterns were classified into negative, apical, and/or cytoplasmic type and stromal type. Thirty-three cases (58%) of group I showed a stromal type, whereas only 17 cases (30%) of group II showed the same type. In undifferentiated type carcinoma, the stromal type was seen in 20 cases (65%) of group I and seven cases (23%) of group II. However, in differentiated type carcinoma, there was only a small difference in the appearance of stromal type between group I (50%) and group II (37%). The immunohistochemical localization for CA19-9 in the tumor tissues, particularly in undifferentiated carcinoma, will be useful in predicting the prognosis of the patients with advanced gastric carcinoma. PMID- 1882798 TI - Rectosigmoid varices and other mucosal changes in patients with portal hypertension. AB - A prospective study was performed to evaluate the prevalence of anorectal varices and their clinical significance as well as to study other proctosigmoidoscopic changes in 75 patients with portal hypertension of diverse etiology. Sixty-seven patients (89.3%) had lower gastrointestinal varices with no significant difference (p greater than 0.05) in prevalence between cirrhosis (92.1%), noncirrhotic portal fibrosis (87%), and extrahepatic portal venous obstruction (85.7%). The rectum was the most common site of lower gastrointestinal varices. External anal and sigmoid colonic varices almost always occurred in the presence of rectal and/or internal anal varices. There was no correlation between the presence of rectosigmoid varices and the severity of esophagogastric mucosal changes or portal hypertension. There was no suggestion that esophageal variceal sclerotherapy influenced the presence of anorectal varices. Seven patients (9.3%) had recent hematochezia, including three patients in whom it occurred in the absence of any upper gastrointestinal hemorrhage. Varices were the cause of bleeding in at least five patients. An abnormal mucosal vascular pattern in the form of telangiectasias or spiders was seen, irrespective of etiology of portal hypertension, in nine patients (12%). Hemorrhoids were present in 31 patients (41.3%) with an age-related difference (p less than 0.05) between patients with cirrhosis (55.3%) and extrahepatic portal venous obstruction (21.4%). PMID- 1882797 TI - Treatment of esophageal varices: low versus high dose of 5% ethanolamine oleate. AB - Twenty-four patients, undergoing sclerotherapy for esophageal varices, were injected with 10-20 ml of ethanolamine oleate 5% in the first treatment session (group A). Fourteen patients were injected with 40 ml of the same sclerosant in the first session (group B). Retrospective analysis was carried out to evaluate the efficacy and safety of the two doses. Variceal eradication was achieved in group B in significantly fewer sclerotherapy sessions. Rebleeding occurred in 16% of patients in group A, compared with no rebleeding in group B. There was no significant difference in the incidence of various complications. We conclude that the use of 40 ml of 5% ethanolamine oleate in the first session is more effective and as safe as the use of 20 ml of the same sclerosant. PMID- 1882799 TI - Duodenal ulcer and Sjogren's syndrome in patients with primary biliary cirrhosis: a casual association? AB - Peptic ulcer has been reported in patients with primary biliary cirrhosis (PBC), but its frequency and pathogenesis are still poorly defined. We have analyzed the occurrence of duodenal ulcer in 37 female patients affected by PBC and in 35 with chronic liver disease of various etiologies. An active ulcer was found in seven patients with PBC and in one with chronic autoimmune hepatitis. The presence of an exocrine gland defect, as indicated by clinical signs of Sjogren's syndrome (SS), was found in six patients with PBC and duodenal ulcer (85%), but in only eight (26.6%) of those without ulcer (p less than 0.02). Therefore, in our patients, duodenal ulcer occurs more often in PBC than in other types of chronic liver disease. The association of SS with PBC, significantly higher in patients with than without ulcer, supports the hypothesis that the underlying exocrine gland defect is involved in the development of duodenal ulcer. PMID- 1882800 TI - Hepatocellular and biliary expression of HLA antigens in primary biliary cirrhosis before and after ursodeoxycholic acid therapy. AB - Recently, there have been reports that ursodeoxycholic acid (UDCA) therapy has a beneficial effect on liver function in patients with primary biliary cirrhosis. However, information regarding the effects of UDCA therapy on hepatic histology remains insufficient. Aberrant expression of HLA antigens on hepatocytes is regarded important in the progression of hepatocellular damages mediated by cytotoxic T-cells in primary biliary cirrhosis. In this study, we examined immunohistochemically hepatocellular expression of HLA antigens on hepatocytes before and after UDCA therapy in four patients with asymptomatic primary biliary cirrhosis. Piecemeal necrosis, intralobular focal necrosis, and portal inflammation, as well as infiltration of activated T-lymphocytes and expression of HLA class I antigens on hepatocytes, disappeared, or diminished in parallel after the therapy. In two of four patients, expression of HLA-DR on some periportal hepatocytes before the therapy also disappeared after the therapy. These observations imply that UDCA therapy decreases the hepatocellular expression of HLA antigens and thereby reduces or abolishes T-cell-mediated hepatocellular necrosis in primary biliary cirrhosis. PMID- 1882801 TI - Acute delta hepatitis: serological diagnosis with particular reference to hepatitis delta virus RNA. AB - To evaluate serologic diagnosis of hepatitis delta virus, we tested HDV RNA in stored sera from 48 patients with acute delta hepatitis who were identified with anti-HD antibodies. Initial sera were positive for HDV RNA in 27 of 48 (56%) patients. In comparison, isolated IgM anti-HD was present in 18 (38%) patients, although IgM and IgG anti-HD were present concurrently in 16 (33%) additional patients. Overall, either HDV RNA or IgM anti-HD was present in 69% of the initial sera. The HDV infection was self-limiting in all except two patients who died of fulminant hepatitis and nine others in whom chronic delta hepatitis ensued. Patterns of HDV seropositivity during progression to chronicity induced variable persistence, disappearance or recrudescence of either HDV RNA or IgM and IgG anti-HD. Results of HDV RNA and IgM anti-HD tests were concordant in only 40 50% of instances. Our results indicate that serological testing for HDV RNA is direct and will demonstrate HDV replication in a large number of cases with acute delta hepatitis. Testing for IgM anti-HD could provide supplemental evidence for HDV infection. Sequential testing for these markers will facilitate assessment of the outcome of acute HDV infection. PMID- 1882802 TI - Transfusion-related chronic liver disease in sickle cell anemia. AB - The medical records and liver biopsies of nine sickle cell patients with chronically elevated liver function tests were retrospectively reviewed to determine the etiology of chronic liver disease. There were eight women and one man with a mean age of 30 yr. All patients had hemoglobin SS. Eight patients were referred for elevated aminotransferases and one for an elevated alkaline phosphatase. Hemosiderosis was present in all of the biopsies. Two patients had cirrhosis. Chronic hepatitis was noted in two patients, and five patients had cholestasis. Two patients had serologic markers demonstrating HBV exposure but no patients were HBsAg positive. Erythrophagocytosis, sinusoidal dilatation, and Kupffer cell hyperplasia were present in all of the liver biopsies. Transfusion related causes were the most common significant pathologic findings in our patients, and appeared to be the etiologies of chronic liver disease in sickle cell patients. PMID- 1882803 TI - The liver in typhoid fever: always affected, not just a complication. AB - The course of liver involvement during the first three weeks of typhoid fever was studied in 20 patients. Previous studies of liver involvement in typhoid fever have not considered the time course of changes. In this study, hepatomegaly was found during the 2nd or 3rd wk more often than in the 1st wk (36% vs. 11%), whereas jaundice was detectable in 9% of patients after the 1st wk, but never before. Alkaline phosphatase, AST, and ALT were raised in 100%, 100%, and 91% of cases, respectively, during the 2nd and 3rd wk but during the 1st wk, only 11%, 89%, and 56% had mild increases. This study shows that, although the clinical picture of hepatitis is unusual, liver involvement is invariably present after the 1st wk, and should not be considered as a complication, but as a feature of the disease. PMID- 1882804 TI - Extensive hepatic granulomas associated with peripheral T-cell lymphoma. AB - A case of T-cell lymphoma presenting with marked hepatosplenomegaly and extensive hepatic granulomas is described. A 55-yr-old female experienced long-term liver damage showing histological triaditis with atypical lymphoid cell infiltration and erythrophagocytosis. The patient developed marked hepatosplenomegaly and eventually died of respiratory failure. Neither systemic lymphadenopathy nor hematological disorder was noted until her death. Autopsy revealed small atypical lymphoid cells positive for T-cell marker, as well as extensive infiltration of generalized organs, including the liver, spleen, and lungs. As a result of diffuse proliferation of atypical lymphoid cell admixed with variable reactive cells, mainly at the T-zone, the lymph nodes underwent effacement of normal architecture; however, the peripheral sinuses and the fibrous capsule remained relatively well preserved. These histological features were consistent with a diagnosis of peripheral T-cell lymphoma (PTL). It is interesting to note that there were numerous epithelioid granulomas admixed with a small number of atypical lymphoid cells within the hepatic parenchyma. The atypical lymphoid cells may be responsible for the granulomatous reaction in the liver. To our knowledge, there have been no other reported cases of PTL that presented with numerous epithelioid granulomas confined to the liver. PMID- 1882806 TI - Reversible symptomatic biliary obstruction associated with ceftriaxone pseudolithiasis. AB - Ceftriaxone, a third-generation cephalosporin, has been associated with the development of sludge or stones in the gallbladders of some patients treated with this medication. Such precipitates, which are usually reversible upon discontinuation of the drug, sometimes cause symptoms, have simulated acute cholecystitis, and have even led to cholecystectomy in some cases. We report the first known instance of biliary obstruction and secondary pancreatitis in association with reversible ceftriaxone-induced pseudolithiasis. PMID- 1882805 TI - Endoscopic removal of inflammatory fibroid polyps of the stomach. AB - Three cases of gastric inflammatory fibroid polyp removed by endoscopic polypectomy are reported. All lesions were located in the gastric antrum or prepyloric region, and their depth was restricted to the submucosa. The correct diagnosis was obtained, and the digestive symptoms disappeared after polypectomy. In contrast to observations in previous reports, we believe these lesions are suitable for removal by endoscopic means, provided they are small in size and strictly submucosal in location. PMID- 1882807 TI - Could recurrent cholangitis after Roux-en-Y hepaticojejunostomy be explained by motor intestinal anomalies? A manometric study. AB - The aim of this study was to describe the motor patterns found in two patients with recurrent cholangitis episodes after Roux-en-Y hepaticojejunostomy. In one patient, cholangitis was due to a stenosis of the anastomosis between the limb and the left intrahepatic bile duct, while motility of the limb, duodenum, and distal jejunum was normal. In the second patient, no anatomical explanation was found for cholangitis attacks. However, although the duodenal motor activity was normal, the motility of the limb and of the jejunum below the jejunojejunal anastomosis was grossly abnormal: permanent minute rhythm, phase IIIs absent or rare and slowly propagated, all motor abnormalities that could promote bacterial overgrowth in the limb. This stresses the interest in performing motor studies of the Roux-limb when cholangitis remains unexplained after Roux-en-Y hepaticojejunostomy. PMID- 1882808 TI - Narrow duct segment distal to choledochal cyst. AB - "Narrow segments" (or stenotic portions) of the common bile duct (CBD) distal to cysts in two patients (a 50-yr-old woman and a 25-yr-old man) with choledochal cyst (CholCyst) were studied macroscopically and histologically. The narrow segments of the ducts were patent and connected with the main pancreatic duct extraduodenally, whereas the CBD in controls were neither dilated nor stenotic, and joined the main pancreatic duct within the duodenal wall. These narrow segments were 1 cm long. In case 1, a minute orifice was found in the narrow segment of the duct macroscopically and was identified microscopically as a small duct from a pancreatic lobule. In case 2, a small pancreatic duct also joined the narrow segment of the duct. These small pancreatic ducts were derived from the ventral pancreas, based on distribution of PP-islets. Therefore, the narrow duct distal to the cyst in patients with CholCyst (or congenital biliary dilatation) was considered to be a branch of the ventral pancreatic duct. PMID- 1882810 TI - Aberrant insertion of the common bile duct into an accessory pancreatic duct: cholangiographic demonstration. AB - Variations in the pancreatic ductal anatomy result from abnormalities in embryological development of the pancreas from ventral and dorsal buds. We describe a case in which cholangiography demonstrated insertion of the common bile duct into an aberrant pancreatic duct. To our knowledge, this finding has not been previously reported in the literature. PMID- 1882811 TI - Defined formula diet for Crohn's disease: can it be used as primary therapy? PMID- 1882809 TI - Successful transcatheter embolization of pseudoaneurysm associated with pancreatic pseudocyst. AB - Hemorrhage into a pancreatic pseudocyst is a rare event, but is the most rapidly lethal complication of chronic pancreatitis. Visceral-vessel aneurysms are an unexpectedly common finding in arteriography of patients with chronic pancreatitis. This case report describes bleeding from an anterior superior pancreaticoduodenal artery aneurysm, caused by chronic pancreatitis. The aneurysm was successfully treated by embolization with a steel coil. PMID- 1882812 TI - Air contrast barium enema versus colonoscopy: the debate continues. PMID- 1882813 TI - Omeprazole therapy modifies the gastric localization of Helicobacter pylori. PMID- 1882814 TI - A simplified diagnostic approach to Helicobacter pylori infection--is it adequate? PMID- 1882815 TI - Colonoscopy during an attack of severe ulcerative colitis. PMID- 1882816 TI - Overt gastrointestinal bleeding in the course of chronic low-dose aspirin administration for secondary prevention of arterial occlusive disease. PMID- 1882817 TI - Is ischemia an etiological factor in chronic pancreatitis? PMID- 1882818 TI - Achalasia: a need for more study. PMID- 1882819 TI - Small intestinal involvement in visceral leishmaniasis. PMID- 1882820 TI - Prevention and treatment of pregnancy-associated hypertension: what have we learned in the last 10 years? AB - High blood pressure (BP) complicates approximately 10% of all pregnancies. Hypertension in pregnancy falls into four categories: (1) preeclampsia-eclampsia, (2) chronic hypertension of whatever cause, (3) preeclampsia-eclampsia superimposed to chronic hypertension or renal disease, and (4) transient or late hypertension (gestational hypertension). Preeclampsia, the association of hypertension, proteinuria, and edema, accounts for more than 50% of all the hypertensive disorders of pregnancy and is a major cause of fetal and maternal morbidity and mortality. Unfortunately, distinguishing between preeclampsia and other causes of hypertension on clinical grounds can be difficult because of the lack of specific tests for differential diagnosis. Increased vascular resistance has been claimed as the primary cause of preeclampsia; however, a variable hemodynamic profile with relatively high cardiac outputs, normal filling pressures, and inappropriately high systemic vascular resistances is now reported by most investigators. Imbalance between vasodilator and vasoconstrictor eicosanoids may account for platelet activation and increased responsiveness to pressor peptides. Altered prostacyclin (PGI2) to thromboxane A2 (TxA2) ratio in maternal uteroplacental vascular bed may favor local platelet activation and vasoconstriction contributing to placental insufficiency and fetal distress. Alternatively, recent evidence seems to suggest that fetal umbilical placental circulation may be the site of the primary vascular injury. Whether low-dose aspirin prevents preeclampsia because it inhibits the excessive maternal TxA2 or whether the partial inhibition of fetal TxA2 is also of therapeutic value remains to be established. Treatment of severe hypertension in pregnancy is probably important to prevent cardiac failure or cerebrovascular accidents in the mother. The need for pharmacological therapy of mild to moderate hypertension is still debated, since no formal studies are available to clarify whether pharmacological treatment in such instances effectively reduces maternal or fetal risk. For the treatment of preeclampsia, hydralazine and nifedipine may be used when delivery is not applicable. Labetalol and diazoxide are effective for hypertensive emergencies. Life-threatening hypertension that does not respond to more conventional therapy is an indication for the use of sodium nitroprusside. For chronic hypertension, alpha-methyldopa remains the treatment of choice; if ineffective, hydralazine or beta-blockers are suitable. Effectiveness and safety of other molecules remain elusive. PMID- 1882821 TI - Hepatitis B virus-associated glomerulonephritis: electron microscopic studies in 98 children. AB - Ninety-eight children with glomerulonephritis concomitant with hepatitis B surface HBs antigenemia were studied, the antigenemia being first documented at the clinical onset of glomerulopathy. Initial diagnoses, based on examination of the paraffin sections, varied, membrano-proliferative, mesangial, and membranous glomerulonephritis being most frequently considered. However, electron microscopic examination showed that 77 children had a uniform type of glomerulopathy, irrespective of the light microscopic appearance. This type was diagnosed as secondary membranous glomerulonephritis. The clinical course of this nephropathy was relatively indolent and short. Moreover, in many children, elimination of some hepatitis B virus (HBV) antigens from the circulation was also associated with clinical remission of glomerulopathy. The remaining 21 children with HBs antigenemia had various morphological forms of glomerulonephritis, these being similar to their idiopathic counterparts in both morphology and clinical course. The distinct clinical and morphological picture of secondary membranous glomerulonephritis with HBs antigenemia occurring in 77 of 98 children supports the hypothesis that HBsV-associated glomerulonephritis is of the secondary membranous type. Thus, we conclude that in children HBV antigenemia associated with glomerulonephritis other than secondary membranous is coincidental. PMID- 1882822 TI - Selective elevation of monomeric IgA1 in IgA nephropathy patients with normal renal function. AB - The molecular form of the pathognomonic IgA in IgA nephropathy (IgAN) remains controversial. Because characterization of the molecular form of IgA molecules can lend insight into their origin (systemic v mucosal), we developed immunoassays to measure both total and J chain-containing (polymeric) IgA1 and IgA2. These assays were used to measure IgA in sera from two groups of IgAN patients (with normal or decreased renal function), as well as from a group of normal individuals. IgA1 levels were higher in both groups of patients with IgAN when compared with the controls. The elevation appeared to be restricted to non-J chain-containing (monomeric) IgA1 in patients with normal renal function, whereas polymeric IgA1 was also slightly elevated in patients whose renal function was diminished. While there were no significant differences between the groups in terms of the levels of total IgA2, the patient group with normal kidney function appeared to have lower levels of polymeric IgA2. The observation that the elevation in serum IgA appears to be restricted to the monomeric form of IgA1, at least when renal function is normal, implies a systemic origin of the pathognomonic IgA in IgAN and further suggests an abnormality in the regulation of IgA secretion by immunoglobulin-producing cells in bone marrow, the site of systemic IgA synthesis. PMID- 1882824 TI - Mortality in dialysis patients: analysis of the causes of death. AB - The objective of this study was to identify the causes of death in maintenance dialysis patients who survived at least 90 days and were monitored during a 16 year period. Of 532 patients starting dialysis, 222 died. The causes of death were grouped into six categories: cardiac, infectious, withdrawal from dialysis, sudden, vascular, and "other." The greatest number of deaths were due to infections, followed by withdrawal from dialysis, cardiac, sudden death, vascular, and other. The risk of dying increased for the first 4 years of dialysis, decreased in years 5 through 10, and had a second increase at 11 years. The mortality during the first 4 years consisted largely of infectious and cardiac deaths. The late peak of deaths was mainly due to infections and withdrawal from dialysis. Overall, infections accounted for more than 36% of all deaths. Withdrawal occurred in 21.2% of the patients and was most common in patients over age 61. Notably, cardiac deaths accounted for only 14.4% of all deaths and no patient died from a cardiac cause after surviving on dialysis more than 8.5 years. We conclude that infection is the leading cause of death in our dialysis patient population. Withdrawal from dialysis was a common cause of death, especially in older patients. Cardiac mortality was not as frequent as anticipated and occurred mainly in patients on dialysis less than 4 years, suggesting that it is the result of preexisting disease. PMID- 1882823 TI - Parathyroid hormone and myocardial performance in dialysis patients. AB - Whether parathyroid hormone (PTH) has a clinically important effect on myocardial performance is unclear. Previous investigations of cardiac function before and after parathyroidectomy have failed to control for ionized calcium, other biochemical parameters, or heart rate and cardiovascular loading conditions. We performed load- and rate-independent measurements of myocardial contractility in seven stable hemodialysis patients before and after surgical parathyroidectomy under identical conditions of blood ionized calcium (Ca2+), electrolytes, pH, PO2, and hematocrit. Mid-molecule PTH decreased from 44 +/- 8 to 2 +/- 1 ng/mL. Aortic systolic and diastolic pressures, left ventricular chamber dimensions, end systolic wall stress, left ventricular contractility at a common level of afterload, and contractile reserve evaluated with dobutamine were similar before and after parathyroidectomy. Thus, PTH appears not to have a direct effect on myocardial contractile state in dialysis patients. PMID- 1882826 TI - Risk factors for tunnel infections in continuous peritoneal dialysis. AB - Little data are available about risk factors for peritoneal catheter subcutaneous tunnel infection. Therefore, we analyzed tunnel infections occurring in our program over a 10.5-year period. One hundred twenty-nine tunnel infections occurred in 92 of 411 patients (22%) on peritoneal dialysis for a mean of 19 +/- 19 months. Tunnel infection rate was 0.19 per year. By 1 year, 15% of patients had a tunnel infection, and by 2 years, 23%. Tunnel infection rates decreased with increasing time on peritoneal dialysis: 2.4 per year for patients on peritoneal dialysis less than 1 year, 0.8 per year for patients on dialysis 1 to 2 years, and 0.4 per year for patients on dialysis greater than 2 years (all different at P less than 0.01). Organisms were cultured in 109 tunnel infections: gram-positive cocci in 77 episodes (71%) [Staphylococcus aureus 57, 52%], and gram-negative bacilli in 24 episodes (22%). Tunnel infection rates were higher in diabetics than in nondiabetics (0.27 per year v 0.16 per year, respectively; P less than 0.001 by life-table analysis of time to first infection) and also higher in women than in men (0.23 per year v 0.17 per year, P less than 0.001). Tunnel infection rates were 0.35 per year for diabetic women, 0.20 per year for diabetic men, 0.18 per year for nondiabetic women, and 0.15 per year for nondiabetic men (groups different, P less than 0.001). Race and age were similar in patients with and without tunnel infections. Catheter loss was 80% when tunnel infection was associated with peritonitis and 40% when tunnel infection alone was present (P less than 0.001). We conclude that the risk of tunnel infection is highest early in the course of peritoneal dialysis and that diabetic women, for unclear reasons, are at the highest risk. PMID- 1882825 TI - Changing patterns of end-stage renal disease due to hypertension. AB - We analyzed the records of all residents of Jefferson County, Alabama, accepted for renal replacement therapy between 1982 and 1987 and compared them with those accepted between 1974 and 1978 to determine any changes in the distribution and frequency of end-stage renal disease (ESRD) due to hypertension (H-ESRD). H-ESRD increased from 6.4 to 9.6 per 100,000 in blacks and from 0.36 to 0.62 per 100,000 in whites. Smoothed age- and race-specific yearly H-ESRD rates decreased in blacks under age 50. Peak incidence of H-ESRD shifted from age 40 to 49 in 1974 through 1978 to age 50 to 59 in 1982 through 1987 (P less than 0.0001). Blacks were referred for care with significantly higher blood pressure levels and serum creatinine concentrations than whites, and had more severe retinal vascular disease. Factors significantly associated with a shorter time from referral to renal replacement therapy were black race, female gender, blood urea nitrogen and serum creatinine concentrations, carbohydrate intolerance, and the use of alpha agonist and/or angiotensin-converting enzyme (ACE) inhibitor. We conclude that racial distribution and risk for H-ESRD have not changed. Peak rates of H-ESRD have been delayed nearly a decade, suggesting a possible effect of better awareness and treatment of hypertension. PMID- 1882827 TI - Increased infection rate in diabetic dialysis patients exposed to cocaine. AB - Three hundred ninety-seven insulin-dependent diabetic dialysis patients were screened by nursing staff for analgesic-seeking behavior. Thirty-eight patients were identified and classified as prescription abusers (n = 26) or illicit drug users (n = 12). The nine cocaine users, when compared with 14 insulin-dependent diabetics on dialysis matched by protocol, were found to be similar in terms of diabetic retinopathy and metabolic neuropathy. Although statistically not significant, cerebrovascular and cardiovascular complications were more common in the study group. Gastroenteropathy with malnutrition was more common the study group (P less than 0.025). Infection rate and severity were markedly worse in the cocaine group: bacterial cellulitis, sepsis, and abscess each increased greater than fourfold. All the visceral infections were in the cocaine-using group. Hepatitis viral antigen and antibody was increased 10-fold in the cocaine users. Recommendations for management of dialysis patients with analgesic-seeking behavior are formulated in light of these findings. PMID- 1882828 TI - Independent effects of cyclosporine and prednisone on posttransplant hypercholesterolemia. AB - To clarify the relative influences of cyclosporine (CsA) therapy, corticosteroid therapy, and other clinical variables on posttransplant hypercholesterolemia, total serum cholesterol levels were measured in 107 renal transplant recipients receiving one of three immunosuppression regimens: CsA and azathioprine (AZA) (group I); CsA, AZA, and prednisone (group II); or AZA and prednisone (group III). Multivariate analysis demonstrated that prednisone therapy, CsA therapy, patient age, and pretransplant cholesterol levels correlated independently with posttransplant cholesterol levels at last follow-up (ranging from 13 to 84 months after transplantation). In 32 patients successfully withdrawn from corticosteroid therapy and maintained on AZA and stable doses of CsA, serum cholesterol decreased from 6.55 +/- 1.1 mmol/L (253.5 +/- 43.1 mg/dL) to 5.27 +/- 1.2 mmol/L (203.9 +/- 45.6 mg/dL). Results of this analysis indicate that prednisone and CsA are independent factors in the pathogenesis of posttransplant hypercholesterolemia. Complete withdrawal of corticosteroids partially corrects hypercholesterolemia in CsA-treated renal transplant recipients. PMID- 1882829 TI - Reduction of remnant nephron hypermetabolism by protein restriction. AB - To study the metabolic mechanisms involved in the protective effect of dietary protein restriction on the progression of chronic renal failure, experiments were performed in Sprague-Dawley rats subjected to five-sixths nephrectomy and pair fed on isocaloric low (4%) protein (LP) or high (50%) protein (HP) diets. Protein restriction reduced the severity of uremia, with lower blood urea nitrogen (BUN) concentrations (8.9 +/- 1.1 v 30.0 +/- 2.9 mmol/L [25 +/- 3 v 84 +/- 8 mg/dL] both n = 12, P less than 0.01), and resulted in lower mortality at 2 weeks (0% v 33%, P less than 0.05), 4 weeks (16% v 58%, P less than 0.05), and 10 weeks (16 v 83%, P less than 0.01). Isolated perfusion of the remnant kidney at 3 weeks demonstrated reduced O2 consumption (QO2) (0.77 +/- 0.2 v 2.56 +/- 0.5 mumol/min/g, both n = 7, P less than 0.05) in the absence of significant differences in inulin clearance (239 +/- 53 v 341 +/- 39 microL/min/g, NS) and net sodium reabsorption (34 +/- 8 v 49 +/- 6 mumol/min/g, NS) in rats fed the LP diet. A lower renal QO2 in protein-restricted animals was also demonstrated in vivo (4.1 +/- 0.9 v 13.8 +/- 2.7 mumol/min/g, P less than 0.01). In vivo P-31 nuclear magnetic resonance (NMR) studies of remnant kidneys did not demonstrate any difference in the steady-state tissue concentrations of adenosine triphosphate (ATP) or inorganic phosphate between rats fed LP and HP diets. Dietary protein restriction decreases the severity of uremia and diminishes renal QO2 in the remnant kidney model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882830 TI - Validation of the cause of renal failure of patients in the Medicare end-stage renal disease program. AB - Studies addressing the epidemiological issues of end-stage renal disease (ESRD) and the implications for health resource allocations are valuable, especially because the Medicare ESRD program is expected to continue growing during the next decade. Studies on trends in the causes of renal failure have benefited from Medicare's extensive data files on ESRD patients. However, no studies have been published that validate the cause of renal failure field in the Medicare files. The primary disease causing renal failure for over 10,000 New York State patients in the Medicare ESRD program was compared with their hospital discharge diagnoses. Of these patients, 8,730 (83%) had a known cause of renal failure in the Health Care Financing Administration (HCFA) data files. Eighty-nine percent of these patients' primary cause of renal failure was matched with the same major hospital diagnostic code. Patients with diabetes and glomerulonephritis had the highest overall match rates (96% to 97%). Patients with polycystic kidney disease and causes of renal failure other than the four major causes had the lowest match rates (75% to 76%), but these match rates increased to 84% to 87% for patients hospitalized more than five times. Some differences in match rate by age and race were found. These findings suggest that HCFA data on the causes of renal failure of ESRD patients are reasonably accurate and can be used successfully to study a variety of issues related to the diseases leading to chronic renal failure. PMID- 1882831 TI - The use of cardiopulmonary resuscitation: how nephrologists and internists differ. AB - We performed a national survey to explore the circumstances under which general internists and nephrologists discuss cardiopulmonary resuscitation (CPR) with patients and the factors influencing physician decisions to open such discussions. We wondered whether nephrology fellowship training and/or formal exposure to an ethics course during training altered physicians' use of CPR. Significantly more nephrologists than internists responded to the study (nephrologists, 174/467; internists, 92/380; P less than 0.01). Few of the respondents participated in an ethics course during training (9% of nephrologists, 15% of internists; P = NS), and fewer than half (26% of nephrologists, 37% of internists; P = NS) had engaged in formal discussions about initiating and withdrawing life-sustaining treatment during their training. Nephrologists spent significantly more time caring for patients in intensive care units (ICUs) (29% v 21% of time, P less than 0.05), and more often discussed CPR during their first meeting with a patient (7% of nephrologists v 1% of internists; P less than 0.05). Twenty-eight percent of nephrologists and 19% of internists thought CPR should be offered to all patients. Both nephrologists and internists rated neurologic dysfunction as the most important and age the least important factor influencing decisions to terminate CPR. Nephrologists were less comfortable than internists with healthy dialysis patients' decisions to refuse CPR. We conclude that nephrologists are more inclined than internists to use CPR in dialysis patients, in patients with impaired functional status, and in all patients. Training in medical ethics did not account for the differences among nephrologists and internists. PMID- 1882832 TI - The supply of renal physicians: an analysis of data from the American Medical Association Physician Masterfile. AB - This study uses data from the American Medical Association (AMA) Physician Masterfile to describe current demographic trends among physicians specializing in adult and pediatric nephrology. The analysis shows that renal physicians are younger than the physician population as a whole. Compared with other specialty groups, renal physicians are less likely to be in patient-care activities and are more likely to be in research. In recent years, the population of renal physicians has grown at a much faster rate than the rest of the physician population. A projection analysis indicates that the adult nephrologist population will more than double in size between 1987 and 2010. Among adult nephrologists, the number of women is expected to grow much faster than the number of men. Rapid growth is expected in the older age categories, whereas the number of adult nephrologists 35 years of age and younger is expected to decrease slightly. PMID- 1882833 TI - Nephrology manpower: the supply side. PMID- 1882834 TI - Renal transplantation for the nephrologist: why we need transplantation medicine. PMID- 1882835 TI - Obstructive acute renal failure by a gravid uterus: a case report and review. AB - Acute renal failure caused from an obstruction by the gravid uterus is a rare complication of pregnancy. Only 13 cases have been reported. We report a case of obstructive acute renal failure in a patient at 34 weeks' gestation with a twin pregnancy complicated by polyhydramnios. The serum creatinine peaked at 1,078 mumol/L (12.2 mg/dL), higher than in the previously reported patients. The striking feature of her clinical course was the immediate resolution of anuria following amniotomy, thus avoiding the need for dialysis, ureteral stenting, or immediate surgical delivery. This patient illustrates the potential importance of increased uterine pressure on the ureters as a cause of significant obstructive renal failure during pregnancy. PMID- 1882836 TI - Agrobacterium radiobacter peritonitis in two patients maintained on chronic peritoneal dialysis. AB - We report two patients with end-stage renal disease maintained on chronic peritoneal dialysis who developed peritonitis in which the infecting organism was Agrobacterium radiobacter, normally a rare pathogen in humans. Both patients initially responded to antibiotics, but later relapsed and required catheter removal. Neither had been exposed to soil or plant material. A radiobacter is yet another of a growing list of unusual organisms that infect the peritoneal cavity of peritoneal dialysis patients. PMID- 1882837 TI - Reflex sympathetic dystrophy syndrome of the hand after placement of an arteriovenous graft for hemodialysis. AB - Reflex sympathetic dystrophy syndrome (RSDS), a complex clinical syndrome characterized by pain and swelling of an affected extremity, is most commonly seen after trauma. We report the case of a woman with diabetes mellitus and chronic renal failure who presented with RSDS 5 months after placement of an arteriovenous (AV) graft for hemodialysis. The temporal relationship between RSDS and the vascular surgery suggests AV graft placement as the precipitating event for the development of RSDS. Treatment with systemic corticosteroids successfully relieved the patient's symptoms. We believe that RSDS should be included in the differential diagnosis of unexplained limb pain and swelling after AV graft placement. PMID- 1882838 TI - The association of IgA glomerulonephritis and thin glomerular basement membrane disease in a hematuric patient: light and electron microscopic and immunofluorescence investigation. AB - A double glomerulopathy (IgA glomerulonephritis [IgAGN] associated with thin glomerular basement membrane disease [TGBMD]) is reported in a 39-year-old woman presenting with macroscopic-microscopic hematuria. Her 3-year-old daughter was also affected by microhematuria of probable glomerular origin. The diagnosis of IgAGN was made by means of immunofluorescence investigation, which showed generalized diffuse mesangial deposits. TGBMD was identified by electron microscopic investigations, which disclosed thinning (up to 160 nm) of basement membrane of several capillary loops and prominence of the lamina densa. Bearing in mind the known frequencies of the two glomerulopathies, their association may not be coincidental, and, therefore, is worthwhile researching in hematuric patients. PMID- 1882839 TI - Peritubular capillary congestion in renal allograft biopsies may be an unreliable marker for cyclosporine nephrotoxicity. PMID- 1882841 TI - Isolation and characterization of the CRIPTO autosomal gene and its X-linked related sequence. AB - We have previously reported on the identification of a cDNA clone encoding a novel human growth factor, named "CRIPTO," that is abundantly expressed in undifferentiated human NTERA-2 clone D1 (NT2/D1) and mouse (F9) teratocarcinoma cells. We now report the organization and nucleotide sequence of two related genomic sequences. One (CR-1) corresponds to the structural gene encoding the human CRIPTO protein expressed in the undifferentiated human teratocarcinoma cells, and the other (CR-3) corresponds to a complete copy of the mRNA containing seven base substitutions in the coding region representing both silent and replacement substitutions. The 440 bp 5' to the CAP site of CR-1 are preserved in CR-3. CR-1 maps to chromosome 3, and CR-3 maps to Xq21-q22. Southern blot analysis reveals that multiple CRIPTO-related DNA sequences are present in the human as well as in the mouse genome. PMID- 1882840 TI - Sequence and localization of a partial cDNA encoding the human alpha 3 chain of type IV collagen. AB - A novel type IV collagen, alpha 3(IV), has recently been identified in human and bovine basement membranes. Here we describe the cloning and sequencing of a cDNA encoding 218 residues of the NC1 domain of the human alpha 3(IV) chain. Of interest is the possible role of abnormalities of the alpha 3(IV) chain in Alport syndrome, as suggested by the failure to detect the NC1 domain of alpha 3(IV) in the basement membranes of some Alport syndrome patients. To determine whether the alpha 3(IV) gene (COL4A3) may be mutated in Alport syndrome, we localized it, by somatic cell hybrid analysis and in situ hybridization of metaphase chromosomes, to chromosome 2q35-2q37. Mutations in alpha 3(IV) cannot therefore be responsible for the vast majority of cases of Alport syndrome, which have been shown to be X linked. One explanation for the immunochemical data implicating alpha 3(IV) in Alport syndrome pathogenesis is that mutations of the alpha 5(IV) chain, which has been localized to Xq22 and found to be mutated in at least three kindreds with Alport syndrome, lead to failure to incorporate the alpha 3(IV) chains into the multimeric structure of glomerular basement membrane in a stable fashion. PMID- 1882843 TI - Isolation of a human DNA sequence which spans the fragile X. AB - To identify the sequences involved in the expression of the fragile X and to characterize the molecular basis of the genetic lesion, we have constructed yeast artificial chromosomes (YACs) containing human DNA and have screened them with cloned DNA probes which map close to the fragile site at Xq27.3. We have isolated and partly characterized a YAC containing approximately 270 kb of human DNA from an X chromosome which expresses the fragile X. This sequence in a yeast artificial ring chromosome, XTY26, hybridizes to the two closest DNA markers, VK16 and Do33, which flank the fragile site. The human DNA sequence in XTY26 also spans the fragile site on chromosome in situ hybridization. When a restriction map of XTY26, derived by using infrequently cutting restriction enzymes, is compared with similar YAC maps derived from non-fragile-X patients, no large scale differences are observed. This YAC, XTY26, may enable (a) the fragile site to be fully characterized at the molecular level and (b) the pathogenetic basis of the fragile-X syndrome to be determined. PMID- 1882844 TI - Marfan syndrome: no evidence for heterogeneity in different populations, and more precise mapping of the gene. AB - Marfan syndrome is a dominantly inherited connective tissue disorder with manifestations in the cardiovascular, ocular, and skeletal systems. The diagnosis is hampered by both high variability in the phenotypic expression and late manifestation of symptoms. The cause of Marfan syndrome remains unknown, but our group has recently reported the genetic linkage of Marfan syndrome to a polymorphic marker on chromosome 15. To analyze the possible heterogeneity behind Marfan syndrome, we have performed linkage analyses for four chromosome 15 markers in 17 families from five different populations: Scottish, English, Swiss, American, and Finnish. By combining the linkage data of all the studied families into a LINKMAP analysis we obtained a maximal LOD score of 11.2, which maps the Marfan syndrome locus between D15S25 and D15S45 on the long arm of chromosome 15. The data reveal no evidence for genetic heterogeneity behind Marfan syndrome and provide us with a more precise location of both the Marfan syndrome locus and flanking markers. This information will provide the basis for the DNA diagnostics of Marfan syndrome in the future. PMID- 1882842 TI - Molecular characterization of variant alpha-subunit of electron transfer flavoprotein in three patients with glutaric acidemia type II--and identification of glycine substitution for valine-157 in the sequence of the precursor, producing an unstable mature protein in a patient. AB - In our previous study of eight glutaric acidemia type II (GAII) fibroblast lines by using [35S]methionine labeling and immunoprecipitation, three of them had a defect in the synthesis of the alpha-subunit of electron transfer flavoprotein (alpha-ETF) (Ikeda et al. 1986). In one of them (YH1313) the labeling of the mature alpha-ETF was barely detectable, while that of the precursor (p) was stronger. In another (YH605) no synthesis of immunoreactive p alpha-ETF was detectable. In the third cell line (YH1391) the rate of variant p alpha-ETF synthesis was comparable to normal, but its electrophoretic mobility was slightly faster than normal. In the present study, the northern blot analysis revealed that all three mutant cell lines contained p alpha-ETF mRNA and that their size and amount were comparable to normal. In immunoblot analysis, both alpha- and beta-ETF bands were barely detectable in YH1313 and YH605 but were detectable in YH1391 in amounts comparable to normal. Sequencing of YH1313 p alpha-ETF cDNA via PCR identified a transversion of T-470 to G. We then devised a simple PCR method for the 119-bp section (T-443/G-561) for detecting this mutation. In the upstream primer, A-466 was artificially replaced with C, to introduce a BstNI site into the amplified copies in the presence of G-470 from the variant sequence. The genomic DNA analysis using this method demonstrated that YH1313 was homozygous for T----G-470 transversion. It was not detected either in two other alpha-ETF deficient GAII or in seven control cell lines. The alpha-ETF cDNA sequence in YH605 was identical to normal. PMID- 1882846 TI - ASHG human genome committee report. The human genome project: implications for human genetics. PMID- 1882845 TI - Complex segregation analysis of nonsyndromic cleft lip and palate. AB - This study was undertaken to examine the inheritance pattern of nonsyndromic cleft lip with or without cleft palate (CL/P). Complex segregation analysis using the unified model as in POINTER and the regressive model as in REGD programs were applied to analyze a midwestern U.S. Caucasian population of 79 families ascertained through a proband with CL/F. In REGD, the dominant or codominant Mendelian major locus models of inheritance were the most parsimonious fit. In POINTER, besides the Mendelian major locus model, the multifactorial threshold (MF/T) model and the mixed model were also consistent with the observed data. However, the high heritability parameter of .93 (SD .063) in the MF/T model suggests that any random exogenous factors are unlikely to be the underlying mechanisms, and the mixed model indicates that this high heritability is accounted for by a major dominant locus component. These findings indicate that the best explanation for the etiology of CL/P in this study population is a putative major locus associated with markedly decreased penetrance. Molecular studies may provide further insight into the genetic mechanism underlying CL/P. PMID- 1882847 TI - X-chromosomal gene in Leber hereditary optic neuroretinopathy. PMID- 1882848 TI - Medical aspects of child labor in developing countries. PMID- 1882849 TI - Translocation of inhaled asbestos fibers from the lung to other tissues. AB - To investigate translocation of asbestos fibers, tissue samples from 13 North American insulators were examined, using electron microscopy. Of the two major types of asbestos, chrysotile and amosite, chrysotile was found to be much more active in the translocation than amosite, being the fiber mainly detected in mesotheliomas and hyaline plaques. PMID- 1882850 TI - Tumors of the urinary bladder in painters: a case-control study. AB - In a case-control study, 403 male patients with a diagnosis of "bladder tumor" and (as controls) 426 patients suffering from prostate disease were investigated. The results of this study indicate that past employment as a painter was associated with an excess risk of bladder tumor. The relative risk of bladder tumor estimated for painters was 2.76. The possible role of benzidine-based azodyes (or azodyes based on substituted benzidines) as a carcinogenic risk factor for painters is discussed. PMID- 1882851 TI - Mortality from asthma, chronic obstructive pulmonary disease, respiratory system cancer, and stomach cancer among paper mill workers: a case-referent study. AB - In an earlier case-referent study from a soft-paper mill with levels of paper dust exceeding 5 mg/m3, an increased mortality was found (OR = 3.8, p less than 0.05) from asthma and chronic obstructive pulmonary disease (COPD) among the employed. Furthermore, other studies on paper mill workers have also indicated an increased mortality from lung cancer. The main objectives of the present case referent study were to investigate the mortality from asthma. COPD, and lung cancer in two other Swedish paper mills. In these mills, the levels of paper dust have been below 3 mg/m3. The subjects for the study were all men who died between 1961 and 1985 from asthma and COPD (n = 31), respiratory cancer (n = 27), and stomach cancer (n = 33) selected in three parishes surrounding two paper mills. As referents we randomly selected about six times as many men who had died from nonmalignant nonrespiratory diseases in these parishes (n = 550). On the basis of information found in the personnel records in the mills, the men were classified into different occupational categories or as unexposed. No increased risk of asthma or COPD was found among the workers exposed to paper dust. However, it was found that there was significantly increased mortality (OR = 5.7, p less than 0.05) for asthma and COPD among workers in a previous log sorting department. The study also showed a significantly increased risk of lung cancer (OR = 2.1, p less than 0.05) among maintenance workers. There was no increased risk of stomach cancer in the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882852 TI - Work-related deaths in children. AB - An analysis of OSHA fatality investigations for 1984-1987 found 104 work-related deaths in children. The largest category (30%) involved industrial vehicles and equipment, followed by electrocution (17%) and falls (11%). Forty-three deaths (41%) occurred while engaged in types of work prohibited for children by the Fair Labor Standards Act (FLSA). Three deaths involved work with conveyors, an activity currently permitted for child workers under FLSA. OSHA issued citations for safety violations in 70% of deaths. Since OSHA investigates only some work related deaths, the actual number of child labor fatalities during the four year period was probably higher. Using information from OSHA and from death certificate data, we estimate that there are at least 100 work-related deaths in the United States in children under 18 each year. Hazardous child labor continues to occur even in industries regulated by OSHA and FLSA. PMID- 1882853 TI - Work injuries and exposures in children and young adults: review and recommendations for action. AB - Child labor, the penultimate form of cheap labor, is endemic in poor countries; it also occurs in affluent countries. Little information has been available on injuries, disease, and effects on growth and development in the tens of millions of children at risk. Preventive and control measures are eliminating the gross abuses, tracing and banning hazardous exposures to toxic agents, eliminating risks of injuries and ergonomic strain, providing health services for working children through the primary health care network, and developing international failsafe design standards for tools and work systems, if these children must work. There is a need to train public health professionals, pediatricians, and maternal and child health care personnel in carrying out simple descriptive epidemiologic studies and setting up interventive programs. Eliminating the worst conditions and controlling hazards where there is no imminent alternative to child labor are suggested as the basis for a two-pronged strategy for protecting children who are forced to work. PMID- 1882854 TI - Chromosomal abnormalities among nurses occupationally exposed to antineoplastic drugs. AB - The effect of handling antineoplastic drugs was examined in 42 nurses working in an oncology department, and the same number of nurses not exposed to antineoplastic drugs acted as controls. The exposure effect was evaluated by analysis of sister chromatid exchanges (SCE) incidence and structural chromosomal abnormalities. SCE as well as chromosomal abnormalities in the exposed group were increased (p less than 0.001 and p less than 0.01, respectively). Sign test for paired sample was used for statistical assessment. PMID- 1882855 TI - Occupational sentinel health events: an up-dated list for physician recognition and public health surveillance. AB - An occupational sentinel health event (SHE[O]) is a disease, disability, or untimely death, which is occupationally related and whose occurrence may: 1) provide the impetus for epidemiologic or industrial hygiene studies; or 2) serve as a warning signal that materials substitution, engineering control, personal protection, or medical care may be required. Following survey of scientific literature, a list of 50 disease conditions linked to the workplace was presented in 1983; these were codable within the framework of the International Classification of Diseases system (ICD-9). Three criteria were used for inclusion: documentation of associated agent(s), of involved industries, and of involved occupations. The up-dated list contains 64 diseases or conditions and a bibliography of literature citations. The list is useful for the practicing physician in occupational disease recognition, for occupational morbidity and mortality surveillance, and as a periodically up-dated database of occupationally related diseases. PMID- 1882856 TI - The politics of OSHA's standard-setting. PMID- 1882859 TI - Comment on "Implications of OSHA's reliance on TLVs in developing the air contaminants standard" by Robinson et al. PMID- 1882858 TI - OSHA-bashing needs rules. PMID- 1882857 TI - Perspectives on what we formerly called threshold limit values. AB - From the point of view of an epidemiologist with experience in community air quality standards, occupational health standards, radiation standards, and water quality standards, reasons are given for discarding the assumption that occupational health protection should be based on threshold concepts. The weakness of worker health protection based on prescription of maximal exposure levels is noted, regardless of whose judgement is used for such levels. PMID- 1882861 TI - Re: "OSHA's reliance on TLVs". PMID- 1882860 TI - Occupational implications of the chlorofluorocarbon ban in Sweden. AB - Limitations on the use of full halogenated chlorofluorocarbons (CFCs) may create occupational environmental problems. These are currently largely unknown, because the toxicology of most CFC substitutes is unknown. Therefore, toxicity testing of CFC substitutes is necessary, and this can best be done before their use commences. Destruction of CFC and materials containing CFC could generate new chemical compounds, especially during incineration. In addition, problems with higher noise and vibration levels may occur when CFC substitutes are employed, and we should keep in mind that occupational environment problems could also develop when new routines are introduced for transporting, storing, and handling new materials. PMID- 1882862 TI - Counterproductive standard setting. PMID- 1882863 TI - Alternative sources of TLVs. PMID- 1882865 TI - Benefits of peer-reviewed publication. PMID- 1882866 TI - Working toward uniformity in evaluation of ADR-reporting programs. PMID- 1882867 TI - Pharmacy participation in exit interviews. PMID- 1882864 TI - Re: implications of OSHA's reliance on TLVs in developing the air contaminants standard. PMID- 1882869 TI - Dental precaution listing needs improvement. PMID- 1882868 TI - Clinical pharmacy term is outdated. PMID- 1882870 TI - Diethyl phthalate not dangerous. PMID- 1882872 TI - Stability papers and equal publishing opportunities. PMID- 1882871 TI - Reassessing patient counseling. PMID- 1882874 TI - Establishing a pharmacy department for a large pediatric hospital: managerial problems, opportunities, and lessons. AB - The process of planning and establishing a pharmacy department in a pediatric hospital is described, and lessons learned from the experience are summarized. Since its founding in 1954, Texas Children's Hospital (TCH) had shared pharmacy services with St. Luke's Episcopal Hospital. The decision to terminate the shared services agreement in the mid-1980s made it necessary for TCH to establish an independent pharmacy department. A director of pharmacy was hired in March 1988, and November 30 of that year was set as the target for implementation of the TCH pharmacy. It was decided that six services--a decentralized unit dose distribution system, an i.v. admixture service, delivery services, ambulatory care services, a formulatory system, and a drug information service--would be offered initially. Decisions concerning department organizational structure and staffing, space allocations, and a computer system were made. A multidisciplinary advisory committee was appointed; one of its responsibilities was to oversee inservice staff training. The pharmacy areas were to be opened on a staggered basis, beginning with the hematology-oncology clinic pharmacy. A number of problems arose immediately following the opening of the central pharmacy, including inaccurate computer profiles, lower-than-estimated productivity resulting from staff members' unfamiliarity with the new system, higher-than estimated patient census, and orders for nonformulary drugs. Delays in drug delivery times were unacceptably high. A crisis-management plan was implemented to cover both short- and long-term problems, and within a few months operations had stabilized. The opening of the intensive-care and sixth-floor satellite pharmacies enhanced decentralized operations and had an important role in improving response times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1882873 TI - Effect of pharmacist participation on a medical team on costs, charges, and length of stay. AB - The financial impact of pharmacist participation on a medical team in a tertiary care teaching hospital was studied prospectively. Two medical teams, one with and one without a pharmacist, operated simultaneously for 11 months. Physicians and a pharmacist on the teams rotated monthly during the first five months of the study. Subsequently, the hospital administrator, who was unaware that the controlled study was under way, permanently assigned an attending physician to the team that did ot have a pharmacist. After patients' discharge, pharmacy costs, pharmacy charges, hospital charges, and length of stay (LOS) were compared for the two teams. Data analysis was separated into four phases: phase 1, during which attending physicians rotated monthly; phase 2, with a permanent attending physician; phase 3, which encompassed the entire 11 months; and phase 4, which encompassed the 11-month period but omitted patients whose LOS exceeded 30 days. Data were analyzed for a total of 619 patients on the two teams. In phase 1, the team with a pharmacist had significantly lower per-patient pharmacy costs, pharmacy charges, hospital charges, and LOS. In phase 2, no significant differences were found between the teams. In phase 3, the only significant difference was that the team with a pharmacist had lower pharmacy costs and pharmacy charges. In phase 4, the team that included a pharmacist had significantly lower pharmacy costs ($105 difference), pharmacy charges ($368 difference), hospital charges ($2065 difference), and LOS (1.3-day difference). Participation of pharmacists on the medical team can significantly reduce pharmacy costs and charges, hospital charges, and LOS. PMID- 1882875 TI - Documentation of cost savings from decentralized clinical pharmacy services at a community hospital. AB - A pilot program designed to justify the costs of clinical pharmacy services through the use of workload documentation cards is described. At this community hospital, defining a philosophy of care was the first step in developing and implementing decentralized services. A patient-specific care model was chosen, and principles of patient-oriented service were outlined. Daily workload documentation cards were designed for recording pharmacist activities; distribution functions were noted on one side, clinical activities on the other. Direct cost savings that could be attributed to the clinical pharmacists' drug therapy recommendations were quantified and recorded on a second form. Sixty three beds in four hospital units were chosen as sites of the pilot effort. At the end of the six-month study, an analysis of the cost-savings forms documented that clinical pharmacist activities produced an average savings of $1.49 per patient day. The break-even point at which pharmacist salary expenses would equal direct cost savings was determined to be one clinical pharmacist per 80 patient beds. A request to expand clinical services at the hospital was granted. By documenting clinical and distributive activities on a simple form and quantifying the savings associated with clinical interventions, this pilot program demonstrated the cost-effectiveness of clinical pharmacy services. PMID- 1882876 TI - Comprehensive therapeutic interchange program in a community hospital. AB - The implementation of a comprehensive therapeutic interchange program is described. The need to reduce the number of telephone calls to physicians about nonformulary drug orders, reduce drug costs, and maximize the effectiveness of drug therapy prompted the development of an automatic therapeutic interchange program at a 273-bed nonteaching community hospital. Pharmacists and physicians agreed that a telephone call to discuss every nonformulary drug order was unnecessary. The pharmacy department presented the automatic interchange program to the pharmacy and therapeutics committee. The program was reviewed by the committee, the hospital attorney, and medical staff members and was instituted in 1986 for drug products, such as vitamins and antacids, for which interchanges are noncontroversial. A newsletter describing the program was distributed, and inservice education sessions were held. A reminder was placed on order forms that an interchange for nonformulary drugs would be made unless the nonformulary agent was deemed "medically necessary" by the physician. In such cases, the physician is contacted to discuss the therapeutic alternative. As acceptance of the program and cost efficiencies were demonstrated, more controversial agents were phased in during subsequent years. It was difficult to obtain approval to add some agents, such as third-generation cephalosporins, to the program, but noncompliance and confusion have been minimal. An automatic therapeutic interchange program has worked well at this institution since 1986. PMID- 1882877 TI - Influence of a decision analysis model on selection of drug therapy. AB - The impact of a decision analysis model on pharmacists' preferences for a drug therapy was studied. Three hundred forty members of the American College of Clinical Pharmacy were randomly assigned to receive either a copy of a drug therapy review alone (control group) or the review plus a decision analysis of the same clinical problem (experimental group). The disease selected was pseudomembranous colitis, and the drugs to be considered were vancomycin, metronidazole, and bacitracin. The review and the decision analysis recommended metronidazole as the best agent. Each subject completed a short questionnaire, read the review or the review plus the analysis, and completed a follow-up questionnaire. Both questionnaires asked the subjects to rank the agents in order of preference. There were 164 usable responses, 86 from the control group and 78 from the experimental group; the total response rate was 48.2%. The difference in the proportion of respondents in each group who chose metronidazole as the most preferred agent, both before and after the intervention, was not significant. Of the 40 experimental-group subjects who ranked metronidazole as their second or third choice in the pretest, 16 (40%) ranked it as the most preferred agent in the posttest. Ten of these 16 stated that the model influenced their decision. Decision analysis plus a drug therapy review had no greater impact on pharmacists' opinions on the selection of drug therapy for pseudomembranous colitis than did the review alone. The model did influence some of those who changed their opinion. PMID- 1882878 TI - Effect of pharmacy-conducted education on prescribing of postoperative narcotics. AB - The effect of written guidelines and pharmacist-conducted education on the prescribing of postoperative narcotics was studied. The postoperative narcotic regimens prescribed on a general surgery ward and patients' assessment of pain control were recorded during three eight-week study phases. After the first (baseline) phase, written guidelines for the use of postoperative narcotics were mailed to all physicians. Four weeks after the baseline phase ended, data were collected again for eight weeks. A pharmacist then began reinforcing the guidelines by presenting inservice educational sessions and participating in ward rounds. The pharmacist did not attempt to change narcotic regimens for individual patients. Four weeks after the pharmacist's efforts began, the final eight-week data-collection period commenced. In general, the appropriateness of narcotic orders increased as the educational efforts intensified. There was no difference in narcotic expenses or pain control among the study phases. The appropriateness of postoperative analgesic regimens increased as education efforts became more intense, but the efforts had no effect on drug expenses or pain control. PMID- 1882879 TI - Use of refractometers to detect controlled-substance tampering. AB - Hospital pharmacies presently lack a simple and cost-effective procedure to monitor the integrity of solutions of controlled substances that they distribute. Thus, the use of refractive-index values, measured by inexpensive hand-held refractometers, in monitoring such solutions was studied. Four refractometers were used to measure the refractive index or % Brix (an index of the percentage of solid in solution) of solutions of a number of controlled substances, including fentanyl citrate, morphine sulfate, hydromorphone hydrochloride, and meperidine hydrochloride. The hand-held refractometers provided precise readings with small variabilities. Although this method does not determine the actual drug concentration per se, subversion of the monitoring procedure for many solutions would require considerable forethought and scientific knowledge. A refractometric survey of 83 controlled-substance solutions returned to the hospital pharmacy showed the procedure to be capable of identifying a solution of unexpected concentration. The described refractometric procedure is rapid, simple, reproducible, inexpensive, and applicable to a wide array of drug solutions. Hospital pharmacies may consider using the procedure for routine monitoring of solutions of controlled substances. PMID- 1882880 TI - Use of ampicillin-sulbactam before and after formulary inclusion. AB - The use of ampicillin-sulbactam before and after the product was formally placed on a hospital formulary is described. In October 1987 the pharmacy and therapeutics committee at an acute-care institution granted ampicillin-sulbactam temporary formulary inclusion on the condition that its use be audited. Formal inclusion was to be based on the results of this preinclusion audit. A second audit was to be performed if formal inclusion was granted. The data were collated after each audit, and for each patient an infectious-disease consultant proposed an alternative antimicrobial regimen representing what would probably have been prescribed had ampicillin-sulbactam not been available. Sixty-four patients received the product during the six-month preinclusion audit period. Ampicillin sulbactam was given to 37% of the patients for indications listed in FDA-approved labeling. The dosage was considered appropriate in 88% of the patients. Clinical outcome was considered successful in 84% of the patients who received the product for known infections. Therapy with ampicillin-sulbactam was less expensive (by $4125) in 35 patients and more costly (by $1523) in 29 patients; the projected annual savings were $7805. After formal inclusion on the formulary, ampicillin sulbactam was prescribed for some 700 patients over a 16-month period. A review in 49 patients showed appropriate indication and dosage for 63% and 84% of the patients, respectively, and an 84% rate of therapeutic success. The extrapolated cost savings were $26,429 per year. After formulary inclusion, the use of ampicillin-sulbactam increased, as did the frequency of its use for indications appearing in FDA-approved labeling. PMID- 1882881 TI - Effect of blood and serum on in vitro antibacterial activity of nitrofurazone. AB - The effect of various volumes of blood and serum on the in vitro antibacterial activity of 0.2% nitrofurazone soluble dressing (NSD) was studied. The antibacterial activity of NSD was tested with an agar well diffusion technique. Zones of inhibition against susceptible strains of Escherichia coli and coagulase positive Staphylococcus aureus were measured with a micrometer. Bacterial concentrations of 10(5) and 10(8) colony-forming units per milliliter were tested to evaluate a possible effect of inoculum size. Wells contained full-strength (undiluted) NSD or 75%, 50%, or 25% NSD dilutions (w/w) in blood, serum, or 0.9% sodium chloride injection. The mean decrease in inhibition zone size produced by blood and serum was only 7.2%. The diminution of activity, albeit small, was statistically significant. The zones produced were still much larger than those associated with clinical cure. Therefore, the impact of blood and serum on nitrofurazone's in vitro antibacterial activity can best be described as a slight reduction in rather than an elimination of effectiveness. This small reduction in activity is unlikely to be clinically important in patients with burns or other surface wounds that contain blood or serum. An effect of inoculum size was demonstrated for both organisms. Blood and serum produced a small but significant reduction in NSD's antibacterial activity in vitro. Controlled clinical studies are needed to ascertain the clinical importance of these findings. PMID- 1882882 TI - Characterization of cisplatin degradation as affected by pH and light. AB - The stability of cisplatin in 0.9% sodium chloride solution was studied. Cisplatin was reconstituted with sterile water for injection to achieve a concentration of approximately 1 mg/mL in 0.9% sodium chloride solution. The solutions were placed in flexible polyvinyl chloride containers, clear and amber glass flasks, and plastic syringes and stored at 22-25 degrees C in the dark or exposed to measured amounts of light and assayed periodically for up to 96 days. The initial pH of some of the solutions was adjusted. The stability of cisplatin in the solutions was determined by measuring the concentrations of cisplatin, trichloroammineplatinate(II) (TCAP), and trans-dichlorodiammineplatinum(II) (transplatin) with high-performance liquid chromatography and by measuring solution pH. The effect of adding ethylene oxide and other materials was also determined. TCAP was identified as the predominant degradation product of cisplatin in all the solutions. The rate of degradation was dependent on pH: In the dark, about 0.04% and 0.21% of the cisplatin degraded to TCAP per week at pH 4.3 and 6.3, respectively. The presence of ethylene oxide accelerated cisplatin degradation. Degradation also occurred during exposure to short-wavelength (350 490-nm) visible light. Storage in amber glass flasks offered more protection than storage in clear flasks. Isomerization of cisplatin to transplatin was not observed. The major degradation product of cisplatin was trichloroammineplatinate(II). Solution pH was the predominant factor affecting cisplatin stability. PMID- 1882883 TI - Activity of urokinase diluted in 0.9% sodium chloride injection or 5% dextrose injection and stored in glass or plastic syringes. AB - The effects of the diluent, the container, the i.v. set, and the drug concentration on the adsorption of urokinase to i.v. administration systems were studied, along with the compatibility of urokinase with plastic and glass syringes. Solutions of urokinase 1500 and 5000 IU/mL in 0.9% sodium chloride injection and 5% dextrose injection in glass and polyvinyl chloride (PVC) containers were sampled at 2 and 30 minutes. Administration sets were attached to PVC containers containing the urokinase-5% dextrose injection solutions, and samples were collected at 90 and 150 minutes. Glass and polypropylene syringes containing urokinase 5000 IU/mL in 0.9% sodium chloride injection or 5% dextrose injection were sampled at 0, 4, 8, and 24 hours. Urokinase activity was measured by an in vitro clot lysis assay. No urokinase diluted in 0.9% sodium chloride injection adsorbed to glass or PVC containers. For urokinase 1500 IU/mL in 5% dextrose injection, a loss of 15% to 20% occurred almost instantaneously in PVC containers; additional losses to the infusion sets were minimal. However, for urokinase 5000 IU/mL in 5% dextrose injection, no losses were observed in the PVC systems. No drug loss to glass bottles was seen for urokinase 1500 or 5000 IU/mL in 5% dextrose injection. Urokinase potency remained constant in polypropylene and glass syringes for 24 hours. To minimize urokinase sorption to PVC containers, higher concentrations of urokinase diluted in 5% dextrose injection should be used, provided that clinical safety and efficacy are not compromised. The use of 0.9% sodium chloride injection as a diluent also prevents sorption losses. PMID- 1882885 TI - Pharmacist-managed medication training in personal-care homes. PMID- 1882884 TI - Waivers for military use of investigational agents. PMID- 1882886 TI - A peer review-based quality assurance system. PMID- 1882887 TI - Pharmacy services on obstetrics and gynecology and neonatology units. PMID- 1882888 TI - Evaluation of serum lithium concentration determinations. PMID- 1882889 TI - Visual compatibility of haloperidol lactate with 0.9% sodium chloride injection or injectable critical-care drugs during simulated Y-site injection. PMID- 1882890 TI - Hospitals' exclusive contractual arrangements with vendors of durable medical equipment violate antitrust laws. PMID- 1882891 TI - Quality assurance for the JCAHO standards. PMID- 1882893 TI - Leadership and professionalism in pharmacy. PMID- 1882892 TI - Influence of methods on the evaluation of therapeutic drug-monitoring services. PMID- 1882894 TI - Treatment of peptic ulcer disease with sucralfate: a review. AB - Sucralfate has been used widely for the treatment of peptic ulcer. Healing rates for duodenal ulcer range from 60 to 90% at 4-6 weeks and up to 90% at 12 weeks for gastric ulcer. The small number of maintenance trials suggest that relapse of duodenal ulcer is reduced comparably to H2 receptor antagonists. There has been considerable interest in the possibility of lower relapse ratios after initial healing with sucralfate compared with H2 receptor antagonists, but more studies of the possible mechanisms as well as larger trials are still needed to confirm these observations. PMID- 1882895 TI - Healing of erosive esophagitis with sucralfate and cimetidine: influence of pretreatment lower esophageal sphincter pressure and serum pepsinogen I levels. AB - Forty-eight patients with erosive reflux esophagitis were allocated to either sucralfate tablets, 4 g/day, or cimetidine, 1.6 g/day, for 8 weeks in a randomized, prospective, single-blind, cross-over therapeutic trial. Pretreatment lower esophageal sphincter (LES) pressure and serum pepsinogen I (PG-I) levels were investigated as possible predictors of healing with either drug. The trial was completed by 41 patients (21 in the sucralfate group and 20 in the cimetidine group); one patient in each group was removed because of side effects. Symptom improvement occurred to a similar extent in both groups. Endoscopic results after 8 weeks of treatment with sucralfate revealed complete healing of esophageal erosions in 48% (cimetidine, 55%) and improvement in an additional 19% (cimetidine, 20%). Neither of these differences was statistically significant. Some patients refractory to one drug had endoscopic healing of esophagitis when treated with the other drug after crossover. LES pressure did not influence outcome in patients treated with sucralfate, whereas significantly (p = 0.024) more patients refractory to cimetidine had an LES pressure less than 7 mm Hg than did those with a good response to the histamine-2 (H2)-receptor blockade. Patients whose esophagitis healed or improved after sucralfate tended to have lower serum PG-I levels than those with treatment failure (104 +/- 35 ng/mL vs 125 +/- 45 ng/mL), whereas the opposite occurred in patients treated with cimetidine (132 +/- 58 ng/mL in responders vs 78 +/- 27 ng/mL in nonresponders, p = 0.048). The results confirm that sucralfate is a valuable alternative to H2 receptor inhibitors for the treatment of reflux esophagitis. They also provide preliminary evidence that LES pressures and serum PG-I levels may have predictive value of the response to one or the other of these two drugs. PMID- 1882896 TI - Sucralfate versus cimetidine in the treatment of reflux esophagitis, with special reference to the esophageal motor function. AB - Sixty patients entered a double-blind clinical trial comparing the effect of 1 g of sucralfate granulate given four times daily and cimetidine, 400 mg twice daily. Twenty-six patients treated with sucralfate and 26 treated with cimetidine were examined with short-term pH monitoring before and after 12 weeks of treatment. Thirty patients, 19 treated with cimetidine and 11 treated with sucralfate, had esophageal motility studied by a radionuclide test before and after 12 weeks of treatment. The efficacy of the treatments was judged by symptoms and endoscopic response after 4, 8, and 12 weeks of treatment. The endpoint healing rate was approximately 60% in both groups and symptoms were relieved in half of the patients in both groups (difference not significant). The effect of the treatments on pH and number of spikes reflected the different pharmacodynamic profiles of the drugs, whereas the mean transit time (MTT) was not changed by the treatments. The residual activity after radionuclide transit in the sitting position was significantly increased after treatment with cimetidine. The data support the hypothesis that primary dysmotility might be involved in the pathogenesis of reflux esophagitis in about 33% of the patients. Possibilities for a combination therapy with sucralfate and cimetidine are stressed. PMID- 1882898 TI - Sucralfate therapy and reflux esophagitis: an overview. PMID- 1882897 TI - Reflux esophagitis therapy: sucralfate versus ranitidine in a double blind multicenter trial. AB - Sucralfate (Sc) suspension 6 g/day and ranitidine (Rn) tablets, 150 mg, were compared in 125 patients in a double-blind, multicenter, endoscopically controlled trial in the treatment of reflux esophagitis. Inclusion criteria were symptomatic reflux (number and severity of attacks) and endoscopic evidence of esophagitis (grades 1 to 4). Clinical assessments were performed on entry, and at 4 and at 8 weeks, and endoscopy was repeated at 8 weeks. Sc suspension and Rn placebo or Sc placebo and Rn tablets were taken on waking and immediately before retiring at night. Of the 125 patients, 27 were withdrawn because of default (Rn = 4; Sc = 14), noncompliance (Rn = 1; Sc = 2), or the development of congestive cardiac failure (Rn = 1), diarrhea (Rn = 1; Sc = 1), nausea (Sc = 1), constipation (Sc = 1), and hematemesis (Sc = 1). Analysis was performed on the remaining 98 patients, 43 of whom had been treated with Sc and 55 with Rn. Heartburn, acid regurgitation, epigastric pain, dysphagia, and chest pain were relieved in 34% vs 40%, 67% vs 72%, 71% vs 57%, and 86% vs 63% for Sc and Rn, respectively. There was no significant difference between the two groups. Endoscopic healing occurred in 47% of the Sc- and in 31% of the Rn-treated patients (chi 2 = 2.50), and healing or improvement was noted in 81% of the Sc- and 64% of the Rn-treated patients. This difference approached statistical significance (chi 2 = 3.73). There was no obvious endoscopic benefit in 8 of the 43 and 20 of the 55 patients in the groups treated with Sc and Rn, respectively. Although the findings with sucralfate and ranitidine in patients with reflux esophagitis completing the trial suggest a benefit of these agents, the absence of a placebo control group and the high default rates, particularly for those receiving sucralfate, preclude any firm conclusions as to relative or specific efficacy of these agents in this condition. PMID- 1882899 TI - Incidence of pneumonia in mechanically ventilated patients treated with sucralfate or cimetidine as prophylaxis for stress bleeding: bacterial colonization of the stomach. AB - Retrograde colonization of the oropharynx from the stomach by microaspiration of gastric fluid is a recently recognized phenomenon associated with increased gastric pH that may result in pneumonia during ventilation therapy. In a prospective study we investigated 104 mechanically ventilated patients in the intensive care unit who were receiving sucralfate (n = 49) or cimetidine (n = 55) for stress ulcer prophylaxis. The incidence of pneumonia was 45.5% (25 patients) in the cimetidine group and 26.5% (13 patients) in the sucralfate group (95% confidence interval 0.98 to 6.97; odds ratio 2.61; p = 0.0549). Mortality rates were 18.4% (9 patients) in the sucralfate group versus 25.5% (14 patients) in the cimetidine group (p = 0.48). The mean pH values of gastric aspirates were significantly lower in patients treated with sucralfate than in patients receiving cimetidine (p = 0.044). The number of colony-forming units of Enterobacteriaceae in gastric aspirates was also significantly lower in the sucralfate group (p = 0.0037). PMID- 1882901 TI - A comparison of sucralfate with placebo in the treatment of esophageal ulcers following therapeutic endoscopic sclerotherapy of esophageal varices--a prospective controlled randomized trial. AB - In 1984 Roark published the first report of a sucralfate treatment of esophageal ulcers after sclerotherapy. Because this was an uncontrolled trial we planned a prospective double-blind placebo-controlled study with 60 patients. After therapeutic paravariceal injection-sclerotherapy of esophageal varices, patients were randomly treated with sucralfate suspension or placebo. Time of treatment was limited to a maximum of 3 weeks and the dosage of sucralfate was 1 g q.i.d. (Ulcogant-Suspension). Healing was assessed by endoscopy at weekly intervals. Fifty-three patients (25 sucralfate, 28 placebo) were evaluable according to the protocol. No patient left the study because of side effects. At the start of the trial, the patients in the sucralfate group showed a larger ulcer area than the placebo group. There was a tendency to faster healing in the sucralfate group, especially in patients with deeper ulcerations. However, there was no significant difference in global healing between both treatment groups after 3 weeks. Sucralfate suspension may be of value in accelerating the healing process in esophageal ulcers after sclerotherapy, especially in patients with deep ulcers. These results should be confirmed in further trials, in which patients should be stratified with respect to their ulcer volume and severity of liver disease. PMID- 1882900 TI - Failure of infection control in intensive care units: can sucralfate improve the situation? AB - Conventional infection control measures in intensive care units (ICUs) are aimed primarily at stemming cross-infections. The role of patients' endogenous flora in the pathogenesis of nosocomial infection and occasional lapses in aseptic technique in ICUs help to explain the frequent failure of the conventional approaches. Newer control strategies include avoiding gastric and oropharyngeal overgrowth of gram-negative bacilli by using sucralfate to avoid gastric alkalinization and/or suppressing nosocomial flora by use of topical antimicrobials. PMID- 1882902 TI - Effects of sucralfate, lansoprazole, and cimetidine on the delayed healing by hydrocortisone sodium phosphate of chronic gastric ulcers in the rat. AB - We have previously shown that chronic sucralfate ingestion stimulates gastric epithelial proliferation in rats, which may explain one of the beneficial effects of sucralfate in healing of peptic ulcers. In a separate study, we have found that chronic steroid administration delays the healing of experimental gastric ulcers in rats. This study was designed to test the beneficial effects of sucralfate, cimetidine, and lansoprazole (AG-1749, a new proton pump inhibitor), on the delayed healing by steroids in rat chronic gastric ulcers. Chronic gastric ulcers were produced in male Wistar rats, weighing 180 g, by the application of 100% acetic acid. The rats were randomly divided into five groups; (1) control, (2) vehicle alone, (3) 10 mg/kg lansoprazole, (4) 500 mg/kg sucralfate, and (5) 100 mg/kg cimetidine. Except for controls, all rats received daily intraperitoneal injections of 2.5 mg/kg hydrocortisone sodium phosphate. Tested drugs were administered intragastrically (lansoprazole and sucralfate) or intraperitoneally (cimetidine) twice a day for 2 weeks. Rats were sacrificed 14 days later and ulcer size was measured. Chronic administration of hydrocortisone sodium phosphate resulted in a significant delay of ulcer healing induced by acetic acid. Treatment with either lansoprazole or sucralfate abolished the deleterious effect of steroids, whereas cimetidine had no effect. These results indicate that lansoprazole and sucralfate overcome the delayed healing by steroids of chronic gastric ulcers in the rat. PMID- 1882903 TI - Prevention of irradiation-induced bowel discomfort by sucralfate: a double-blind, placebo-controlled study when treating localized pelvic cancer. AB - Sucralfate, an aluminum hydroxide complex of sulfated sucrose used in the treatment of gastric ulcer, was shown to prevent irradiation-induced diarrhea and bowel discomfort significantly in patients treated for pelvic cancer with external radiotherapy with intent to cure. The double-blind placebo-controlled study included 70 patients with carcinoma of the prostate and urinary bladder without distant metastasis (T1-4NO1xMO) and performance status of greater than or equal to 90% Karnofsky scale. Radiotherapy was administered in a conventional manner with MeV photons and a four-field technique. The total dose was 62-66 Gy and total treatment time of 6.5 weeks. Dose granules of sucralfate or placebo were dispensed to each patient 2 weeks after radiation started and continued for 6 weeks. All analyses were performed blindly. Seven of 34 evaluable patients in the placebo group and 18 of 32 evaluable patients in the sucralfate group did not present with diarrhea during the observation period. The frequency of defecation and stool consistency were significantly improved by sucralfate. Fourteen patients in the placebo group and only three in the sucralfate group required symptomatic therapy with loperamide. There was no evidence of adverse effects associated with the use of sucralfate. Sucralfate can be of beneficial value in diminishing the bowel discomfort during radiotherapy of pelvic malignancies, and the earlier proposed mechanisms of action (e.g., protection of denuded mucosa, cytoprotective properties, binding bile acids) can also be valid for the current effects of sucralfate. PMID- 1882904 TI - Role of acid milieu in the gastroprotective and ulcer-healing activity of sucralfate. AB - Sucralfate prevents the formation of acute gastric lesions induced by various ulcerogens and enhances the healing of chronic gastroduodenal ulcerations, but the mechanism of these effects has not been fully explained. This study was designed to determine the importance of intragastric pH in the sucralfate-induced gastroprotection against 100% ethanol, acidified aspirin, taurocholate, or stress, and in the healing of chronic gastroduodenal ulcerations induced by acetic acid. Sucralfate acidified to pH 2.0 showed significantly stronger protective activity against all four irritants, its protective potency against 100% ethanol being about eight times greater and the duration of the protection about four times longer than those obtained with sucralfate at its pH of 5.0. Pretreatment with indomethacin to suppress mucosal generation of prostaglandin or the removal of salivary glands to eliminate the endogenous source of epidermal growth factor failed to affect sucralfate-induced gastroprotection. In contrast, the rate of healing of chronic gastric ulcerations was significantly delayed by indomethacin or sialoadenectomy; but sucralfate enhanced the healing, and a marked inhibition of gastric acid secretion by ranitidine did not eliminate this enhancement. We conclude that the protective activity of sucralfate depends on the presence of acid milieu in the stomach, but that the ulcer-healing effects of this drug occur even after a marked inhibition of gastric acid secretion. PMID- 1882905 TI - A common physical basis for the gastric mucosal barrier and the action of sucralfate. AB - A novel explanation for the action of sucralfate in gastric ulcers has been proposed based on a new theory for gastric mucosal protection derived, in effect, from the very common industrial practice of adsorbing surfactants to surfaces needing protection against acid. Standard physical tests have been employed to show that sucralfate is highly surface-active at both liquid and solid interfaces, with the capability to be adsorbed--but not as active as the indigenous surface-active phospholipid (SAPL). This finding can explain the ability of sucralfate to "bind" to an ulcer site. Unlike SAPL or surfactants in general, adsorbed sucralfate does not render hydrophilic surfaces hydrophobic, suggesting a dual role in substituting for both SAPL and the mucus needed to stabilize it. Electron microscopy, using a novel fixation procedure specifically designed to allow for the known properties of any gastric mucosal barrier, revealed essentially the same oligolamellar lining of SAPL as previously reported in rats. Prolonged (16-day) exposure to sucralfate did not appear to change the situation, whereas there were as many, if not more, lamellar bodies (freshly secreted SAPL) adjacent to the stomach wall. Mucus-free oxyntic ducts showed the same oligolamellar lining as controls. An interesting new finding was the presence of oligolamellar SAPL as the intergranular matrix of gastric mucus--as though preparing to protect the next layer in anticipation of the surface mucin granules being eroded. PMID- 1882907 TI - Comparative study of sucralfate 2 grams twice daily versus sucralfate 1 gram four times daily in the treatment of benign gastric ulcers in outpatients. AB - In a double-blind, randomized study, we compared the healing of gastric ulcer during a twice-daily regimen of 2 g sucralfate or sucralfate 1 g q.i.d. Patients receiving the former therapy received the tablets one-half hour before breakfast and at bedtime. Patients receiving sucralfate 1 g q.i.d. received their therapy 30 minutes before breakfast, lunch, and supper, and at bedtime. The study included 52 patients with endoscopically proven gastric ulcer; 41 patients completed the study. Healing was endoscopically assessed at 8 weeks and 12 weeks. After 8 and 12 weeks the healing rate for sucralfate 2 g b.i.d. was 67% and 92%, respectively; the healing rate of sucralfate 1 g q.i.d. was 59% and 71%, respectively. No statistically significant difference was found between the two regimens. The results suggest that 2 g sucralfate twice daily is as effective in the healing of gastric ulcer as 1 g sucralfate q.i.d. PMID- 1882906 TI - Comparison of sucralfate and ranitidine in the treatment of duodenal ulcers. AB - Ninety patients with endoscopically proven duodenal ulcers, enrolled in this prospective, single-blind study, were randomized to sucralfate, 1 g q.i.d., 0.5 hour before meals on an empty stomach or at bedtime, or ranitidine, 150 mg b.i.d., for 4-8 weeks (phase I). Patients who healed during the treatment period were invited to participate in a maintenance therapy follow-up covering 1 year (phase II), during which they were treated with sucralfate, 1 g b.i.d. (before breakfast and at bedtime) or 150 mg of ranitidine at bedtime. After 4 weeks of treatment, healing rates were 30/40 (75.0%) with sucralfate and 36/42 (85.7%) with ranitidine, and healing rates were 39/40 (97.6%) and 40/42 (95.2%) respectively, after 8 weeks of treatment. At the end of the 6th and 12th months of phase II, respectively, relapse rates were 3/33 (9.4%) and 10/32 (31.3%) in the sucralfate group and 5/33 (15.2%) and 10/29 (34.5%) in the ranitidine group. Differences between sucralfate- and ranitidine-treated groups were not significant. Both treatments were well tolerated. We conclude that sucralfate is as effective and safe as ranitidine in the short-term treatment and prevention of relapse in patients with ulcer disease. PMID- 1882908 TI - Clinical efficacy of sucralfate in the treatment of gastric ulcer. AB - We performed a randomized, single-blind study in Japan to investigate the efficacy and safety of two dosage regimens of sucralfate granules, 2 g, twice daily (b.i.d. group, n = 30) and 1 g, 4 times daily (q.i.d. group, n = 27), on ulcer healing in 57 patients with endoscopically proven gastric ulcer. Endoscopy was performed after 4 weeks and, if complete healing was not achieved, again after an additional 4 weeks. Of 57 patients, 11 were excluded from the statistical analysis because of protocol violation (six in b.i.d. group, five in q.i.d. group). Of 46 patients eligible for the analysis of healing rates, four patients in the b.i.d. group (all at 8 weeks) and five patients in the q.i.d. group (two at 4 weeks and three at 8 weeks) were withdrawn due to patients' inconvenience. As the possibility that the withdrawals were due to the treatment failures could not be denied, we used the Kaplan-Meier method and generalized Wilcoxon test/logrank test for the calculation and evaluation of healing rates in this study, respectively. Healing rates at 4 and 8 weeks were 50% and 94% in the b.i.d. group and 35% and 68% in the q.i.d. group. There was no significant difference in healing rates between the groups. No serious adverse effect was observed in either group. These results suggest that the 2 g b.i.d. dose of sucralfate in granule form is at least as effective as the conventional dose of 1 g q.i.d. in the treatment of active gastric ulcers and could lead to better patient compliance. PMID- 1882909 TI - Maintenance therapy with sucralfate in duodenal ulcer: genuine prevention or accelerated healing of ulcer recurrence? AB - We sought to compare the efficacy of sucralfate to placebo for the prevention of duodenal ulcer recurrence and to determine that the efficacy of sucralfate was due to a true reduction in ulcer prevalence and not due to secondary effects such as analgesic activity or accelerated healing. This was a double-blind, randomized, placebo-controlled, parallel groups, multicenter clinical study with 254 patients. All patients had a past history of at least two duodenal ulcers with at least one ulcer diagnosed by endoscopic examination 3 months or less before the start of the study. Complete ulcer healing without erosions was required to enter the study. Sucralfate or placebo were dosed as a 1-g tablet twice a day for 4 months, or until ulcer recurrence. Endoscopic examinations once a month and when symptoms developed determined the presence or absence of duodenal ulcers. If a patient developed an ulcer between monthly scheduled visits, the patient was dosed with a 1-g sucralfate tablet twice a day until the next scheduled visit. Statistical analyses of the results determined the efficacy of sucralfate compared with placebo for preventing duodenal ulcer recurrence. Comparisons of therapeutic agents for preventing duodenal ulcers have usually been made by testing for statistical differences in the cumulative rates for all ulcers developed during a follow-up period, regardless of the time of detection. Statistical experts at the United States Food and Drug Administration (FDA) and on the FDA Advisory Panel expressed doubts about clinical study results based on this type of analysis. They suggested three possible mechanisms for reducing the number of observed ulcers: (a) analgesic effects, (b) accelerated healing, and (c) true ulcer prevention. Traditional ulcer analysis could miss recurring ulcers due to an analgesic effect or accelerated healing. Point-prevalence analysis could miss recurring ulcers due to accelerated healing between endoscopic examinations. Maximum ulcer analyses, a novel statistical method, eliminated analgesic effects by regularly scheduled endoscopies and accelerated healing of recurring ulcers by frequent endoscopies and an open-label phase. Maximum ulcer analysis reflects true ulcer recurrence and prevention. Sucralfate was significantly superior to placebo in reducing ulcer prevalence by all analyses. Significance (p less than 0.05) was found at months 3 and 4 for all analyses. All months were significant in the traditional analysis, months 2-4 in point prevalence analysis, and months 3-4 in the maximal ulcer prevalence analysis. Sucralfate was shown to be effective for the prevention of duodenal ulcer recurrence by a true reduction in new ulcer development. PMID- 1882911 TI - Acid secretory changes and early relapse following duodenal ulcer healing with ranitidine or sucralfate. AB - Controversial aspects relating to acid secretory changes following duodenal ulcer healing, and the effect of histamine-2 (H2)-receptor blockers on such changes are discussed. Recent studies comparing the effects of ranitidine or sucralfate on changes in the acid secretory responses in the healing of duodenal ulcers are described, and the relevance of these changes to early relapse considered. The duration of therapy and timing of acid-secretory studies and endoscopies are standardized in all studies, but the acid-secretory parameters vary. These comprised acid secretory responses to graded doses of an intravenous infusion of pentagastrin or histamine, sham-feeding responses, and basal and nocturnal acid secretion. In all studies, healing with sucralfate was associated with a significant decrease in the various parameters of acid secretion. In the ranitidine-healed groups, no appreciable decrease was noted and there was, indeed, a significant increase in nocturnal acid secretion. Routine endoscopies performed 4-6 weeks after documented ulcer healing showed a recurrence of 3 of the 32 (9%) sucralfate-healed and in 14 of the 35 (40%) ranitidine-healed ulcers. Increased acid secretory responsiveness following duodenal ulcer healing was strongly correlated with subsequent early relapse. PMID- 1882912 TI - Fenestrated sheen macular dystrophy. AB - We examined a family with fenestrated sheen macular dystrophy. The red macular lesions were strikingly apparent in the propositus and more subtle in one affected cousin. Pronounced macular retinal pigment epithelial disruption or mottling was present in the father of the propositus, who also had markedly reduced electroretinogram rod and cone responses. The extent of electroretinogram amplitude reduction indicates abnormal function of the peripheral retina in addition to the clinically evident macular changes. Affected family members showed peripheral retinal pigment epithelial granularity. Central visual acuity remained normal despite the presence of macular lesions. PMID- 1882913 TI - Glass-slide vitrectomy for use by the cataract surgeon. PMID- 1882910 TI - Acid secretory responses and parietal cell sensitivity following duodenal ulcer healing with omeprazole, sucralfate, and Maalox. AB - Acid secretory responses and parietal cell sensitivity (PCS) have been studied in 21 duodenal ulcer patients before and after successful treatment with omeprazole (n = 7), sucralfate (n = 7), or Maalox (n = 7). The second study was carried out 3 days after documented healing and withdrawal of treatment in the sucralfate- and Maalox-treated groups and 14 days after documented healing and withdrawal of treatment in the omeprazole-treated patients. Acid output (mmol/hour) was measured as basal secretion, and in response to 0.1 microgram/kg/hour pentagastrin (low-dose) and 6.0 micrograms/kg/hour pentagastrin (high-dose) stimulation. PCS was calculated as the ratio of low dose:high dose acid output (expressed as a percentage). Ulcer healing with sucralfate resulted in significant (p less than 0.05) decreases in low-dose acid output from 36.4% (13.2 51.0) (median [range]) to 8.4% (3.2-45.4) mmol/hour and PCS from 69.1% (44.9 91.4) to 22.0% (16.0-85.6), whereas no significant decreases in any of the measured parameters were noted following ulcer healing with Maalox. Ulcer healing with omeprazole resulted in significant (p less than 0.05) decreases in basal acid output from 6.3 (1.5-22.9) (median [range]) to 2.2 (0-6.9) mmol/hour, and low-dose acid output from 31.0 (6.0-58.0) to 23.0 (1.4-44.8) mmol/hour. These findings suggest that acid secretory responses following ulcer healing vary according to the therapeutic agent used. PMID- 1882914 TI - In defense of animal research. PMID- 1882915 TI - A comparison of penetrating keratoplasty to epikeratoplasty in the surgical management of keratoconus. PMID- 1882917 TI - Detection of antibodies against Borrelia burgdorferi in patients with uveitis. AB - We determined the antibody response against Borrelia burgdorferi strains isolated from Japanese Ixodes ovatus and Ixodes persulcatus ticks by enzyme-linked immunosorbent assay and indirect immunofluorescence assay of serum specimens from 127 patients with uveitis. We examined samples of serum from Japanese patients with unclassified uveitis, iridocyclitis caused by herpes zoster virus, Behcet's disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, or other conditions (sympathetic ophthalmia, Posner-Schlossman syndrome and acute anterior uveitis with ankylosing spondylitis). Serum from healthy individuals and patients with Lyme disease served as negative and positive control samples, respectively. Significantly higher antibody titers were demonstrated in patients with uveitis than in control subjects. Of 29 patients with unclassified uveitis, nine (31) had significantly increased antibody titers against B. burgdorferi strain H014 by ELISA testing. Five patients also showed higher IgG and IgM responses than in three control subjects with Lyme disease. All positive controls showed joint problems characteristic of rheumatoid arthritis. One of three patients had uveitis. The patients were diagnosed as having Lyme disease on the basis of their history and serologic tests. A positive antibody response was recognized in several patients with Behcet's disease, Vogt-Koyanagi-Harada syndrome, sarcoidosis, and other conditions (acute anterior uveitis with ankylosing spondylitis), but not in control subjects. PMID- 1882916 TI - A multicenter study of Pneumocystis choroidopathy. AB - We studied 21 patients with the acquired immunodeficiency syndrome and presumed Pneumocystic carinii choroidopathy. The lesions were characteristically yellow to pale yellow in color, appeared at the level of the choroid, and were found in the posterior pole. They varied in size from 300 to 3,000 microns, initially increasing in number before treatment and eventually resolving after systemic antimicrobial therapy. Of the 21 patients, 18 (86%) had received inhaled pentamidine as prophylaxis against Pneumocystis pneumonia. Visual acuity and visual field testing showed little evidence of retinal destruction. Survival after the diagnosis of the choroidopathy ranged from two to 36 weeks. Pneumocystic choroidopathy offers an easily accessible clue to disseminated Pneumocystis infection. When comparing drugs for Pneumocystis prophylaxis, careful ocular examination can provide one indicator of the relative efficacy of protection against extrapulmonary disease. PMID- 1882918 TI - Congenital arteriovenous communications and the development of two types of leaking retinal macroaneurysms. AB - We treated a patient with a rare combination of congenital arteriovenous communications and the development of leaking macroaneurysms of different types. Initially, leaking macroaneurysms developed in the shunt area of the arteriovenous communication; later, a preexistent fusiform macroaneurysm in the afferent arteriole of the congenital communication started leaking. Because exudates and fluid from the leaking macroaneurysms reached the fovea, laser treatment was performed to obliterate the macroaneurysms. We assume that after obliteration of the macroaneurysms with laser in the shunt area, the increase of hydrostatic pressure on the thin wall of the fusiform aneurysm of the afferent artery led to its leaking. We saw no signs of vascular occlusion after laser treatment. PMID- 1882920 TI - Identifying progression of subclinical keratoconus by serial topography analysis. AB - We performed serial slit-lamp examinations and topography analysis on a patient whose initial topographic map suggested a diagnosis of keratoconus to us but which others interpreted as normal topography. Topography analysis documented cone progression during a two-year period. The initial map showed a cone apex power of 44.5 diopters located 2.1 mm inferior to the vertex normal. An oblong shaped area of maximum power was surrounded by concentric bands of lower power. Corneal surface power ranged from 41.5 to 44.5 diopters. Two years later cone apex power increased to 51.0 diopters, and the patient developed a Fleischer's ring, Vogt's striae, and mild visual aberration. Our findings suggest the use of topography analysis systems in documenting subclinical cone progression. Topography systems may be a useful tool in the study of the true incidence and natural progression of subclinical keratoconus. PMID- 1882921 TI - Ocular infections associated with Comamonas acidovorans. AB - Comamonas acidovorans (Pseudomonas acidovorans) is a ubiquitous gram-negative rod. Although generally considered nonpathogenic, we found C. acidovorans to be associated with six cases of ocular infections. The organism was the only isolate in three cases, whereas an association of other organisms was present in three cases. The multiple resistance patterns of these strains to antibiotic susceptibility testing emphasizes the need for culturing ocular infections. We recommend the identification and susceptibility testing of all ocular gram negative rod isolates. PMID- 1882919 TI - Ultrastructural and immunohistochemical features of coronal adenomas. AB - We studied by electron microscopy three coronal adenomas discovered incidentally in eyes removed surgically. Tumor cells displayed prominent intercellular interdigitations with numerous desmosomes, mitochondria, abundant rough endoplasmic reticulum, and nuclei with membrane infoldings and a granular chromatin pattern. In these characteristics, the tumor cells were identical to nonpigmented ciliary epithelium of the ciliary processes. These growths contained abundant extracellular material, which showed a dimorphic pattern of complex reduplicated basal lamina and granular areas without structure. Immunohistochemical studies on formalin-fixed, paraffin-embedded coronal adenomas demonstrated type IV collagen and laminin in the extracellular material. These findings confirm that coronal adenomas develop from nonpigmented ciliary epithelium and that the extracellular material of these tumors contains components normally present in basement membranes. PMID- 1882922 TI - Diode laser compared with argon laser for trabeculoplasty. AB - A randomized prospective study on two groups of ten patients compared the efficacy of diode laser and argon laser trabeculoplasty. In the diode laser group the intraocular pressure was 23.0 +/- 3.97 mm Hg before the treatment, 20.2 +/- 4.49 mm Hg at two hours, 16.3 +/- 3.13 at six months, and 16.9 +/- 2.80 mm Hg at one year. The differences from baseline were statistically significant at six months (P = .0001) and at one year (P = .0001) but not at two hours. In the argon laser group the intraocular pressure was 23.4 +/- 3.6 mm Hg before the treatment, 22.7 +/- 4.35 mm Hg at two hours, and 17.6 +/- 4.53 mm Hg at six months. One patient had uncontrolled mean high intraocular pressure and underwent surgery. In the nine patients who completed the study the intraocular pressure at one year was 16.7 +/- 3.00 mm Hg. The differences from baseline were significant at six months (N = 10; P = .0001) and 12 months (N = 9; P = .0001) but not at two hours. Differences between the two groups were not significant at two hours, six months, and one year. Laser trabeculoplasty may be effectively with a diode laser. PMID- 1882924 TI - Diurnal intraocular pressure after successful primary laser trabeculoplasty. AB - In 20 patients who were successfully treated with laser trabeculoplasty as the primary therapy for glaucoma, we measured the intraocular pressure every two hours between 8:00 A.M. and 8:00 P.M. Success was defined as intraocular pressure of 22 mm Hg or less without medication. Of 20 patients, three had open-angle glaucoma and 17 had exfoliative glaucoma. Intraocular pressure was stable with small fluctuations during the daytime. PMID- 1882923 TI - Evaluation of once-daily levobunolol 0.25% and timolol 0.25% therapy for increased intraocular pressure. AB - In a three-month, double-masked, randomized clinical trial, we evaluated the once daily ocular hypotensive efficacy of 0.25% levobunolol and 0.25% timolol in 80 patients with open-angle glaucoma or ocular hypertension. Thirty-seven of the 39 patients (95%) in the 0.25% levobunolol group and 35 of the 41 patients (85%) in the 0.25% timolol group successfully completed the three-month study period. The overall mean decrease in intraocular pressure was 5.3 mm Hg (22%) in the 0.25% levobunolol group and 5.4 mm Hg (22%) in the 0.25% timolol group. This difference was not statistically significant. In both treatment groups, effects on mean heart rate and blood pressure were minimal. The data suggest that levobunolol 0.25% and timolol 0.25%, administered once daily, are equally effective in the treatment of open-angle glaucoma and ocular hypertension. PMID- 1882925 TI - Cytopathologic diagnosis of benign lesions simulating choroidal melanomas. AB - In three cases of benign pigmented lesions (one melanocytoma and two pigment epithelial adenomas) there was evidence of tumor growth and the lesions were referred to us as uveal melanomas. The fine needle aspiration biopsy specimens were correctly interpreted in the operating room as being benign tumors. The pigment granules in these benign pigmented lesions are much larger than are observed in uveal melanomas. When they were visible through the heavy pigmentation, the cellular detail appeared benign. In two cases the tumors were successfully resected with cyclochroidectomy techniques and the visual outcome was good. The third eye was studied after it had been removed at another institution. Fine needle aspiration biopsy can often differentiate a benign simulating pigmented lesion from uveal melanoma. PMID- 1882927 TI - The laser step in early glaucoma therapy. PMID- 1882926 TI - Symptomatic retinoschisis-detachment involving the macula. AB - We treated three patients (four eyes) in whom posteriorly situated retinoschisis detachments became symptomatic because of elevation of a limited area of full thickness retina at the macula adjacent to these lesions. Laser photocoagulation alone was successful in achieving long-term macular reattachment in one eye but failed in both eyes of a bilaterally affected patient. In this patient, retinal cryopexy, external drainage of subretinal and retinoschisis cavity fluid, and intravitreal air injection attained long-term macular reattachment and retinoschisis cavity collapse in both eyes. In the third patient, cryopexy, drainage of subretinal and retinoschisis cavity fluid, and scleral buckling failed to reattach the retina. Subsequent laser photocoagulation induced reabsorption of subretinal fluid but without retinoschisis cavity collapse. Alternative management strategies for these unusual cases include retinal cryopexy alone and vitrectomy techniques. PMID- 1882928 TI - Central retinal artery occlusion in a child after general anesthesia. PMID- 1882929 TI - Management of exudative retinal detachment after plaque therapy for intraocular melanoma. PMID- 1882930 TI - Severe anaphylactic reaction to orally administered fluorescein. PMID- 1882931 TI - Hepatic cirrhosis as a cause of eyelid retraction. PMID- 1882933 TI - Bilateral follicular conjunctivitis as a manifestation of Lyme disease. PMID- 1882932 TI - Response of reactivated ligneous conjunctivitis to topical cyclosporine. PMID- 1882934 TI - Horner's syndrome as a complication of pacemaker insertion. PMID- 1882935 TI - Fate of the fellow eye after Propionibacterium acnes endophthalmitis. PMID- 1882936 TI - Decrease in the risk of bilateral acute retinal necrosis by acyclovir therapy. AB - We reviewed the course of 54 patients who had unilateral acute retinal necrosis at initial examination. Thirty-one patients were treated with acyclovir, whereas 23 were not. Of the 31 patients treated with acyclovir, 27 (87.1%) had fellow eyes that remained disease-free throughout a median follow-up of 12 months. Of the 23 patients not treated with acyclovir, seven (30.4%) had fellow eyes that remained disease-free throughout a median follow-up of 11 months. Survival analysis indicated that the fellow eyes of the group of patients treated with acyclovir were more likely to remain disease-free than the fellow eyes of the group not treated with acyclovir (P = .0013). Two years after initial onset, the proportion of fellow eyes that remained disease-free was 75.3% for the group treated with acyclovir and 35.1% for the group not treated with acyclovir. These results suggest that acyclovir treatment reduces the risk of involvement of the fellow eye in patients with acute retinal necrosis. PMID- 1882937 TI - Retinal function and rhodopsin levels in autosomal dominant retinitis pigmentosa with rhodopsin mutations. AB - We studied rod and cone function in 20 patients from six families with autosomal dominant retinitis pigmentosa, who represented five different point mutations in the gene encoding rhodopsin. In a family with a stop codon mutation at the carboxyl end of the molecule (glutamine-344), young members with the mutation were asymptomatic and clinically unaffected but showed about 1 log unit of rod sensitivity loss across the visual field and decreased rhodopsin levels; at this stage, cone function was essentially normal. In three families with mutations at the border of a transmembrane segment (arginine-135-leucine and arginine-135 tryptophan), there was neither detectable rod function nor measurable rhodopsin; cone function was variably impaired. Two families carrying different mutations (threonine-17-methionine and threonine-58-arginine) had altitudinal visual field defects with less impaired rod and cone function in the inferior than in the superior field. Rod adaptation was abnormal in both families, but the time course of adaptation differed between patients with the two mutations. Differences in the pattern of retinal dysfunction were therefore discernible in patients with different rhodopsin mutations. PMID- 1882938 TI - B-scan ultrasonography of eyes containing intravitreal gas. AB - Contact B-scan ultrasonography was performed on postoperative eyes containing intravitreal gas. Correlation of the ultrasonograms with the ophthalmoscopic findings disclosed that intraocular gas had a characteristic appearance on B-scan ultrasonography. Gas-fluid and gas-tissue interfaces were so highly reflective that no structures within or behind a bubble could be visualized. Shadowing, reverberation, and reflection artifacts were prominent, and dominated ultrasonographic findings. If the ultrasonographic characteristics of gas are understood, it is possible to use B-scan ultrasonography to determine if intraocular gas is present, whether there are one or several bubbles, and what percentage of the vitreous cavity is filled by gas. Specular reflection from a gas-fluid interface may be used to examine portions of the eye that might not otherwise be easily seen with ultrasonography. PMID- 1882939 TI - Anterior chamber aspirate cultures after uncomplicated cataract surgery. AB - We cultured anterior chamber aspirates of 30 patients who had uncomplicated extracapsular cataract extraction or phacoemulsification. The aspirate was obtained at the time of wound closure. Of 30 patients, 13 (43%) had culture positive anterior chamber aspirates. The total number of organisms recovered was 18, with three patients having multiple organisms identified. The most commonly isolated organisms were coagulase-negative Staphylococcus sp., occurring in eight of 18 isolates (44%). No eyes in our study developed endophthalmitis, even though almost one half had viable organisms growing from the anterior chamber aspirates. Inoculum sizes were extremely small (10 to 20 colony-forming units/ml). This study suggests that in humans, the anterior chamber is capable of clearing a low inoculum of bacteria after cataract surgery without the development of endophthalmitis. PMID- 1882940 TI - Lens capsule and epithelium in age-related cataract. AB - On the basis of preoperative assessment of patient characteristics, intraoperative obtainment of a lens-capsule and epithelium specimen, histopathologic investigation of lens capsule and epithelium, and biochemical analysis of glutathione reductase in lens epithelium, age-related cataract was studied in 50 adult patients who underwent consecutive extracapsular cataract posterior chamber lens implant surgery. Patients (25 men and 25 women; age range, 41 to 91 years; mean age, 75 years) had a wide range of systemic and ocular disease; 17 of 50 (34%) patients had a history of severe vision-impairing cataract in a first-degree relative. Anterior lens-capsule thickness ranged from 10 to 22 microns, with a mean of 17 microns. Statistical analysis of lens epithelium ultrastructure in 41 of 50 specimens documented mixing of normal and abnormal cells, verified a gradation in the degree of abnormal ultrastructural features, and demonstrated a statistically significant decrease in epithelial cytologic activity with advancing age (P = .038). Biochemical analysis documented a severe glutathione reductase deficiency in nine of 39 (23%) lens-epithelium specimens, possibly reflecting a dietary deficiency of riboflavin. PMID- 1882941 TI - Isolating the effects of primary open-angle glaucoma on the contrast sensitivity function. AB - We evaluated spatial contrast sensitivity functions in age-matched and lens density-matched healthy eyes, eyes with primary open-angle glaucoma, and eyes with ocular hypertension. We also controlled for refraction, visual acuity, pupil size, and previous ocular history. We found an overall reduction in contrast sensitivity for the glaucomatous eyes with a significant difference at 12 cycles per degree (P less than .012). Eyes with ocular hypertension were not significantly different from normal eyes. Significant differences were noted at several spatial frequencies with less careful controls for age and lens effects. We concluded that spatial contrast sensitivity may be a useful adjunctive diagnostic test for glaucoma, but interpreting the results without other clinical data may lead to errors in diagnosis. PMID- 1882942 TI - Anterior uveitis and hypopyon. AB - We undertook a study to determine the incidence of hypopyon, as well as the most common anterior uveitis entities with which hypopyon is associated. A total of 216 patients with anterior uveitis were studied. The uveitis was acute in 155. Of the 155 patients, 11 (7.1%) had hypopyon. Nine of the 11 patients with hypopyon were positive for HLA B27. Of these nine, two had Reiter's syndrome and one had ankylosing spondylitis; the other six had no confirmed systemic disease. Of the two patients with hypopyon who were HLA B27-negative, one had mixed connective tissue vascular disease, and one had idiopathic anterior uveitis. Of the 155 patients with acute anterior uveitis, 62 were HLA B27-positive. Thus, the incidence of hypopyon uveitis among HLA B27-positive patients was 14.5% (nine of 62 patients), whereas the incidence among HLA B27-negative patients was only 2.2% (two of 93 patients). These results suggest that HLA B27-related anterior uveitis is the most common cause of hypopyon uveitis, and that most patients with anterior uveitis associated with hypopyon will test positive for HLA B27. Although these results reflect a referral population, they should be of benefit in the treatment of patients with anterior uveitis. PMID- 1882943 TI - Infectious crystalline keratopathy caused by Candida albicans. AB - Two patients developed corneal opacities resembling infectious crystalline keratopathy. Predisposing factors included a recent corneal transplant with suture replacement in one patient and postradiation keratoconjunctivitis with disposable therapeutic contact-lens wear in the other patient. Both patients were using a topically applied corticosteroid and an aminoglycoside antimicrobial. Smears of corneal scrapings showed numerous yeasts without inflammatory cells. Culturing yielded Candida albicans and Staphylococcus haemolyticus in the first case and C. albicans and S. epidermidis in the second case. Combined antifungal and antimicrobial therapy, with initial withdrawal of corticosteroid use, was effective. The microbial cause of pauci-inflammatory keratitis includes not only viridans streptococci and other bacteria but fungi as well. PMID- 1882944 TI - The effect of corneal hypesthesia on the duration of proparacaine anesthetic eyedrops. AB - The duration of action of proparacaine is known in the normal cornea but not in the hypesthetic cornea. To determine this, we examined both eyes in seven patients with documented unilateral corneal hypesthesia associated with inactive herpetic disease. Cochet-Bonnet measurements were made in both eyes before and at two- to five-minute intervals after the instillation of one drop of 0.5% proparacaine until baseline corneal sensitivity levels were again achieved. Mean recovery time was 34.86 minutes in eyes with normal corneal sensitivity, compared to 45.43 minutes in hypesthetic corneas. In all patients, the recovery time was remarkably longer in the hypesthetic eye than it was in the normal fellow eye. These data demonstrate the need to wait up to one hour after the instillation of proparacaine in eyes suspected of having corneal hypesthesia if corneal sensitivity is to be determined accurately. Additionally, the duration of action of topically instilled anesthetic may be a useful method of discovering subtle differences in corneal sensitivity. PMID- 1882945 TI - Conjunctival ophthalmomyiasis caused by the sheep nasal botfly (Oestrus ovis) AB - Three patients had conjunctival ophthalmomyiasis caused by the ovine nasal botfly. All patients had a sudden onset of redness, tearing, and foreign-body sensation of the affected eye. One to nine Oestrus ovis first-instar larvae were removed from the bulbar or palpebral conjunctiva of each patient. Symptoms and clinical signs resolved after mechanical removal of the larvae. Specific taxonomic diagnosis of O. ovis larvae was determined on the basis of characteristic conformation of the terminal end of the larval caudal segment as seen by use of light microscopy. PMID- 1882946 TI - Human immunodeficiency virus disease epidemiology and nosocomial infection. PMID- 1882947 TI - Development of scleral ulceration and calcification after pterygium excision and mitomycin therapy. PMID- 1882948 TI - Parinaud's oculoglandular syndrome simulating lymphoma. PMID- 1882949 TI - Ocular sarcoidosis manifesting as an anterior staphyloma. PMID- 1882951 TI - Retinal telangiectasis in scapuloperoneal muscular dystrophy. PMID- 1882950 TI - Spontaneous reattachment of a total retinal detachment in an infant with microphthalmos and an optic nerve coloboma. PMID- 1882952 TI - Interferon alpha 2a for treatment of age-related macular degeneration. PMID- 1882953 TI - Spontaneous filtration blebs in a patient with microspherophakia. PMID- 1882954 TI - Differential intraocular pressure in restrictive strabismus. PMID- 1882955 TI - Corneal autografts for external knots in transsclerally sutured posterior chamber lenses. PMID- 1882956 TI - The elastic properties of the lens capsule in capsulorhexis. PMID- 1882957 TI - Prevalence of lattice degeneration and its relation to axial length in severe myopia. PMID- 1882958 TI - Identification, prevention, and treatment of silicone oil pupillary block after an inferior iridectomy. PMID- 1882959 TI - Scleritis and Wegener's granulomatosis in children. PMID- 1882960 TI - A magnetic resonance imaging study of the upshoot-downshoot phenomenon of Duane's retraction syndrome. PMID- 1882961 TI - Flying after otologic surgery. PMID- 1882962 TI - Gadolinium-enhanced magnetic resonance imaging of the facial nerve in herpes zoster oticus and Bell's palsy: clinical implications. AB - Gadolinium-enhanced magnetic resonance imaging was used in the evaluation of the facial nerve in four patients with idiopathic facial paralysis and six with herpes zoster oticus (HZO). Enhancement of the facial nerve was seen in all patients with Bell's palsy, and 50 percent of patients with HZO. The most consistent area of enhancement in both disorders involved the premeatal and labyrinthine segments. Although the images showed changes consistent with the type of viral process that is known to occur in these disorders, we found no significant correlation between the intensity or pattern of facial nerve enhancement on the images, the severity or duration of the disease, or the patient's prognosis for recovery. Nevertheless, gadolinium-enhanced MRI does have a place in the evaluation and decisions for management of select cases of facial paralysis. PMID- 1882964 TI - Pre- and postoperative hearing thresholds and brainstem responses in patients with acoustic neuroma: follow-up study using the middle fossa approach. AB - Forty-one patients with acoustic neuromas were operated by the middle fossa route. Postoperative hearing was maintained in 31 percent within 20 dB of preoperative thresholds. The clinical, audiologic, and neurotologic data of these patients are reported. The acoustic evoked brainstem responses had a tendency to normalise within 2 to 6 months following surgery. In individual cases, hearing function was improved. PMID- 1882963 TI - Microfissures of the temporal bone: do they have any clinical significance? AB - Microfissures extending from the inner ear to the middle ear are a common temporal bone finding. Recently they have been implicated as a possible cause of sudden sensorineural hearing loss. We examined 34 temporal bones and related the presence or absence of microfissures to sudden sensorineural hearing loss. No relationship was found. PMID- 1882965 TI - SN10 auditory evoked potential revisited. AB - The slow brainstem response (SN10) was originally described as a slow negative wave occurring at a latency of 10 msec post stimulus onset. In the late 1970s and early 1980s it was considered to be promising for estimating hearing thresholds at low frequencies. However, there have been controversies regarding waveform description, recording stimulus parameters, and factors affecting the response. Consequently, the SN10 has not become a popular clinical test for estimating hearing thresholds electrophysiologically. However, recent observation of ABR waveforms using low-frequency stimuli and broad-band filtering indicate that the negative wave after wave V can be highly identifiable. This wave in many instances is the SN10. Therefore, this article was designed to review various aspects of the SN10 to make clinicians more aware of its possible applications in estimating low-frequency hearing thresholds. PMID- 1882966 TI - Endolymphatic sac surgery for refractory luetic vertigo. AB - The clinical symptoms of otitic syphilis, either congenital or acquired, are indistinguishable from Meniere's disease. In most cases the symptoms can be controlled by long-term and intensive medical treatment with penicillin and steroids. However, in some cases, luetic vertigo is refractory to such medical regimens, and surgical intervention may become necessary. We report on endolymphatic sac procedures performed on 37 patients with presumed luetic vertigo refractory to medical treatment, between March 1980 and December 1987, with follow-up ranging from 2 years to 9 years and 9 months. Results show that vertigo was completely and substantially controlled in 81 percent of cases, with 2 patients showing improvement in hearing, as assessed with AAO-HNS criteria. It is concluded that endolymphatic sac surgery is appropriate in treating refractory luetic vertigo when intensive medical therapy is unsuccessful, particularly in cases of late or tertiary-acquired lues, such as in this series. PMID- 1882968 TI - Effect of sodium fluoride on early stages of otosclerosis. AB - The present investigation evaluates the effectiveness of NaF treatment in modifying the natural course of subclinical otosclerosis, as monitored by the stapedius reflex. The study was carried out on 128 relatives of patients suffering from surgically confirmed footplate otosclerosis. The diagnosis of subclinical otosclerosis was made on the basis of presence of the on-off effect. One group of subjects was treated with NaF in doses ranging from 6 to 16 mg according to age. The treatment lasted 2 years. A second group served as a control. Changes in stapedius reflex morphology were evaluated at 1, 2, and 5 years from the onset of treatment. The investigation demonstrated that NaF has a stabilizing effect on early otosclerosis. This drug, in fact, arrests the disease process in more than 60 percent of ears at the 2-year follow-up and in more than 50 percent at 5 years. A program of secondary prevention of otosclerosis by NaF is suggested. PMID- 1882967 TI - Tinnitus as a function of duration and etiology: counselling implications. AB - Based on the data of 528 tinnitus patients, information is presented concerning: (a) conditions and/or activities that affect tinnitus severity, (b) tinnitus symptoms as a function of etiology, and (c) changes in tinnitus symptoms as a function of time since onset. The four most common conditions and/or activities that reduce tinnitus severity were sleep, listening to TV/radio, being in noise, or being in quiet. Many conditions and/or activities increased tinnitus severity. The most common detrimental activities and/or conditions were noise exposure, being in a quiet place, emotional stress, loss of sleep, and physical exhaustion. Results also revealed that tinnitus loudness and severity increased as a function of years since onset. However, tinnitus pitch tended to remain stable. Meniere's patients experienced more annoyance, depression, and interference with sleep and also reported louder tinnitus than other etiologies. Tinnitus counselling should include: (a) informing patients that it is unlikely tinnitus annoyance will change dramatically, (b) alerting patients to the usefulness of tinnitus self help groups, (c) helping patients to minimize time spent in activities and/or conditions where tinnitus severity is increased and to maximize time in activities and/or conditions where tinnitus severity is decreased, and (d) stressing the avoidance of noise exposure because of the relationship between noise-induced hearing loss and tinnitus. PMID- 1882969 TI - Inflammatory pseudotumor of the facial nerve as a cause of recurrent facial palsy: case report. AB - This is a report of a case presenting recurrent facial palsy due to inflammatory pseudotumor of the facial nerve. The patient was a 41-year-old man suffering from facial palsy on the right side once in 1983, which recurred in 1988. The initial facial palsy was cured after conservative treatments including steroid administration. Three months after the recurrence, the same treatments were attempted without noticeable effect. He was referred to our clinic two and half months later. Electromyographic examination indicated pronounced denervation of the facial nerve. Imaging study including high resolution CT and MRI revealed a mass lesion around the geniculate ganglion. Facial neuroma was initially suspected. Surgical exploration revealed a tumor involving the geniculate ganglion and the horizontal portion of the facial nerve. The tumor was resected through a combined transmastoid and middle cranial fossa approach, followed by nerve grafting. Histologically, the tumor proved to be an inflammatory pseudotumor originating from the nerve sheath, although the etiologic factor causing the inflammation was not verified. PMID- 1882971 TI - Metastatic atrial myxoma to the temporal bone: case report. AB - A 25-year-old male underwent right mastoid surgery for removal of a soft tissue mass. At age 29 a left cardiac atrial myxoma was excised. At age 34 an expanding right supra-auricular mass with extension into the middle and posterior fossa necessitated total temporal bone resection. Pathology proved to be myxoma. Retrospective review of tissue obtained from the initial mastoid procedure was also myxoma. The temporal bone lesion was considered to be persistent and metastatic atrial myxoma. A review of atrial myxomas and this most unusual metastatic presentation is discussed. PMID- 1882970 TI - Progressive hereditary deafness with predominant inner hair cell loss. AB - This paper presents the first case of human genetic hearing loss due to predominant inner hair cell damage investigated by psychoacoustic audiometry, auditory brainstem responses (ABR), evoked acoustic emissions (EAEs), and distortion product otoacoustic emissions (DPOEs). The genetic transmission was an autosomal dominant inheritance. The audiogram pattern was a dominant high frequency hearing loss. EAE and DPOE properties were normal. Bronx waltzer mutant mouse with genetically determined predominant inner hair cell defects provide an interesting model to study this congenital deafness. This rare congenital deafness with predominant damage to inner hair cells cannot be detected by neonatal screening techniques using EAEs or DPOEs. PMID- 1882972 TI - Voluntarily retractable tympanic membranes: case report. AB - A very rare case of a 7-year-old boy, who was in the habit of voluntarily controlling his hearing acuity by bilaterally retracting his tympanic membranes, is reported. Although normal A type tympanograms were initially observed, B type tympanograms and a decrease in hearing acuity to a hearing level of 35 dB on both sides was seen when he sniffed with both nostrils pinched (the reverse Valsalva maneuver). The patient would repeat the action on such occasions as when he wanted to concentrate on playing computer games while his mother was watching TV with the volume up, while he was swimming, or when the surroundings were noisy between lessons at school. When he wanted to normalize hearing, he would adjust the position of the tympanic membranes by performing the Valsalva maneuver. The patient probably had incomplete closure of the eustachian tube. The eustachian tube could be locked by high negative middle ear pressure induced by the reverse Valsalva maneuver, which resulted in a decrease of hearing acuity caused by retraction of the tympanic membranes bilaterally. PMID- 1882974 TI - Evaluation of acute vertigo: unusual lesions imitating vestibular neuritis. AB - The acute onset of vertigo is a common clinical problem presenting to primary care physicians or otologists for evaluation. Usually the underlying disease process is benign and self-limited in nature. In the absence of hearing loss or additional neurologic findings, a common initial diagnosis is vestibular neuritis. The patient is treated symptomatically and observed for spontaneous resolution. However, other more serious disease processes may mimic the presentation of vestibular neuritis and be misdiagnosed. Five cases of serious central nervous system disorders that were similar to vestibular neuritis in their initial presentation are reviewed to illustrate this point. Each patient presented with the acute onset of continuous vertigo without associated hearing loss. The correct diagnosis was established only after further evaluation was pursued. Recommendations for the initial and subsequent evaluation of these patients are discussed. PMID- 1882973 TI - Physical therapy program for vestibular rehabilitation. AB - Dizziness and balance disorders are among the most frustrating problems for many physicians to treat. Traditional interventions such as medication or surgical procedures offer limited improvement for many patients. Although generic habituation exercises have existed for years, the merits of vestibular rehabilitation are only beginning to be recognized. Current retrospective studies indicate that 85 percent of patients with chronic vestibular dysfunction gain at least partial relief of their symptoms after undergoing vestibular rehabilitation, with approximately 30 percent of patients being completely cured. This modality provides a valuable and rational complement to current established methods of treating the patient with dizziness. Many physicians and physical therapists may be unfamiliar with these new techniques and require clarification of the actual therapeutic approaches in use. This article describes the current evaluation and treatment approach utilized in the vestibular rehabilitation program at the University of Michigan Medical Center. PMID- 1882975 TI - Excellent spontaneous recovery following temporal bone fracture with loss of nerve excitability. PMID- 1882977 TI - Management of facial paralysis following skull trauma. PMID- 1882978 TI - Spondyloarthropathy: erosive arthritis in representative defleshed bones. AB - Erosive changes and syndesmophyte formation, characteristics of spondyloarthropathy, were present in 79/2906 skeletons in the Todd Collection. Holistic assessment of this defined population allowed it to be distinguished from rheumatoid and other erosive forms of arthritis. Characterization of the nature and distribution of osseous alterations in a contemporary skeletal population allowed development of a standard for recognition of the disease in skeletal populations. PMID- 1882976 TI - Management of facial spasm following traumatic facial palsy. PMID- 1882979 TI - Femoral lengths and stature in Plio-Pleistocene hominids. AB - This study reports the femoral lengths of 31 Plio-Pleistocene hominids dated between 3.1 and 0.7 million years ago, and uses those lengths to estimate stature by way of the femur-stature ratio reported by Feldesman et al. (Am. J. Phys. Anthropol. 78:219-220, 1989). By this method the average female Australopithecus afarensis is 105 cm and the average male is 151 cm. The respective values are 115 and 138 cm for A. africanus. As defined by Howell (In VJ Maglio and HBS Cooke (eds): The Evolution of African Mammals. Cambridge: Harvard University Press, 1978) and Johanson et al. (Kirtlandia 28:1-14, 1978), Homo habilis is a sexually dimorphic species, with females standing 118 cm and males 157 cm. Such apparently strong dimorphism may be due to the possibility that there are actually two species of nonrobust hominids between 2 and 1.7 m.y.a. The estimate for the female Australopithecus boisei is 124 cm and for the male, 137 cm, but these estimates are especially difficult to be certain of because there are no femora that can be positively identified as male A. boisei. Australopithecus robustus is estimated to be 110 cm (female) and 132 cm (male). African Homo erectus stood 160 cm (female) and 180 cm (male). From these estimates several generalizations are apparent. First, there is apparently strong sexual dimorphism in stature in A. afarensis and H. habilis, but less in the other species. Second, the "robust" australopithecines were relatively small statured. Third, it is apparently not true that humans have been getting progressively taller throughout their evolutionary history. Some individuals were as tall as modern humans 3 m.y.a., by 2 m.y.a. one individual stood about 173 cm, and by 1.7 m.y.a. a stature of 180+ cm was not uncommon. PMID- 1882980 TI - Detection of significant demographic differences between subpopulations of prehispanic Maya from Copan, Honduras, by survival analysis. AB - Heterogeneity and small sample size are problems that affect many paleodemographic studies. The former can cause the overall distribution of age at death to be an amalgam that does not accurately reflect the distributions of any of the groups composing the heterogeneous population. The latter can make it difficult to separate significant from nonsignificant demographic differences between groups. Survival analysis, a methodology that involves the survival distribution function and various regression models, can be applied to distributions of age at death in order to reveal statistically significant demographic differences and to control for heterogeneity. Survival analysis was used on demographic data from a heterogeneous sample of skeletons of low status Maya who lived in and around Copan, Honduras, between A.D. 400 and 1200. Results contribute to understanding the collapse of Classic Maya civilization. PMID- 1882981 TI - Craniofacial configuration and postcranial development of a hydrocephalic child (ca. 2500 B.C.-500 A.D.): with a review of cases and comment on diagnostic criteria. AB - Hydrocephalus is a severe disorder of the central nervous system characterized by absorption blockage of the cerebral spinal fluid (CSF). The archaeological record of the condition ranges in time from 10,000 B.C. to 1670 A.D. and consists of 30 possible cases worldwide. A review of this material reveals that diagnostic criteria which fully delineate the condition have not been established. Previously, no attempt has been made to differentiate the two major categories of hydrocephalus and their subgroupings, or to identify other conditions which might result in similar morphologies. A partial child's skeleton from the Middle Period (ca. 2500 B.C. to 500 A.D.) of Central California Prehistory is described in light of an extensive clinical literature. Examination of this individual reveals a unique craniofacial configuration and malformed postcrania. Bony criteria for a differential diagnosis of hydrocephalus are established and applied to this individual. Based on these criteria, the individual is diagnosed as having a chronic form of noncommunicating hydrocephalus. Blockage of the CSF pathway most likely occurred in the aqueduct of Sylvius with a partial occlusion of the foramen of Monro or a frontal cyst. In addition, femoral development is suggestive of partial paralysis. PMID- 1882982 TI - Biomechanical association of dental and temporomandibular pathology in a medieval Nubian population. AB - An analysis of the relationship between oral pathology and degenerative change at the temporomandibular joint (TMJ) was undertaken on an archaeological sample of 122 adult crania from the Medieval site of Kulubnarti in Sudanese Nubia. The crania were sorted into 2 groups: those demonstrating clearly visible bony changes at the joint (TMJ+) and those without visible change (TMJ-). These groups were compared according to 1) age; 2) sex; 3) active dental pathologies (abscesses, caries, partial socket resorption); 4) tooth loss with complete socket resorption; and 5) dental attrition. No statistically significant association was evident between degenerative change at the TMJ and age, active dental pathologies, or dental attrition; however, sex differences and posterior tooth loss with complete socket resorption revealed a significant correspondence to degenerative TMJ changes. Both of these factors agree with the clinical literature and with biomechanical models (most notably that of Hylander) based upon modern populations. Furthermore, the results support the contention that paleopathological conditions can be analyzed from a clinical and functional biomechanical perspective. PMID- 1882983 TI - What's old and new in molecular phylogenetics. AB - While it is fairly easy to devise a phylogenetic tree based on molecular data, it has proven difficult to tell how reliable any such tree is. Thus while the genetic inference that humans, chimpanzees, and gorillas cluster together is widely accepted, the genetic inference that the primary division among Old World human populations is between Asia and EurAfrica is not. A molecular phylogenetic inference linking humans and chimpanzees was proposed in the 1980s based on the technique of DNA hybridization. Despite several recent publications in primary and secondary source material, much confusion still exists surrounding the work. This paper tries to clarify issues that may still be confusing to physical anthropologists, and proposes criteria upon which to judge the robusticity of a phylogenetic inference based on DNA hybridization, in light of a recent published claim of replication. The claim of replication is considered critically. Interestingly, the original DNA hybridization data may actually show a chimp gorilla link, in harmony with other phylogenetic results. PMID- 1882984 TI - Sex assessment using the proximal tibia. AB - The proximal end of the human tibia is sexually dimorphic. Tibial condyles from 100 individuals in the Hamann-Todd Collection were measured. Regression equations retrodicted known sex with 86-95% accuracy. A test sample of 20 individuals also from the Hamann-Todd Collection was classified with 85-100% accuracy. A sample of 20 prehistoric individuals provisionally sexed by using crania and innominate bones was classified with 85-100% agreement. Thus, the proximal tibia may be useful in determining the sex of a skeleton. PMID- 1882985 TI - Brief communication: on the optimum number of metacarpals for roentgenogrammetric measurement. PMID- 1882986 TI - Brief communication: Morphometric data for adult lion-tailed macaques (Macaca silenus). AB - Basic morphometric data were collected from 22 adult lion-tailed macaques (M. silenus) of both sexes. M. silenus is a rare primate species from which adequate morphometric data have not heretofore been available for comparative purposes. Data collected include measures of gross body size (weight; crown-rump and rump heel length), and for males, measures of secondary sexual characteristics (canine tooth and testes size). Degree of sexual dimorphism was marked, with males significantly larger and heavier than females. The three body size measures were correlated for males but not for females. There was substantial variation among individual males in secondary sex characteristics measurements. The data indicate than lion-tailed macaque morphometrics are consonant with the general pattern of positive allometry for body size and sexual dimorphism characteristic of the primate order. PMID- 1882988 TI - Humane values and biopsychosocial integration. PMID- 1882987 TI - Looking ahead: new psychiatry, old values. PMID- 1882989 TI - Elissa P. Benedek, M.D. one hundred nineteenth president, 1990-1991. PMID- 1882990 TI - Body dysmorphic disorder: the distress of imagined ugliness. AB - OBJECTIVE: Body dysmorphic disorder, a preoccupation with an imagined defect in physical appearance, has a rich tradition in European psychiatry but has been largely neglected in the United States. Because this little-known disorder is probably more common than is generally realized and can have profound consequences, the author reviews its history, clinical features, and possible relationship to other psychiatric disorders. DATA COLLECTION: Data sources consisted of the MEDLINE database and relevant references in articles obtained from this search. Of 145 articles and books obtained, 100 were selected for inclusion in this review on the basis of how closely they conformed to the concept of body dysmorphic disorder as defined in DSM-III-R and how substantially they contributed to an understanding of the disorder's history, clinical features, or nosologic status. FINDINGS: Body dysmorphic disorder has been colorfully described in the European literature for more than a century. Although its concerns might sound trivial, this disorder can lead to social isolation (including being housebound), occupational dysfunction, unnecessary cosmetic surgery, and suicide. The most commonly associated psychiatric disorder appears to be depression. Although a definitive treatment does not exist, preliminary evidence suggests that serotonergic antidepressant medications may be useful. Whether body dysmorphic disorder is related to other psychiatric disorders, such as psychosis, mood disorder, social phobia, or obsessive-compulsive disorder, is unclear at this time. CONCLUSIONS: More research on the nosology, clinical features, and treatment response of body dysmorphic disorder is important, given the distress and impairment this often secret disorder can cause. PMID- 1882991 TI - Psychodynamics of suicide, with particular reference to the young. AB - OBJECTIVE AND METHOD: The article reviews the literature on the psychodynamics of suicide, focusing on factors that will help in evaluating and treating the young suicidal patient. Articles published in refereed journals and books and book chapters based on such articles are the source of most of the material. Articles that first brought a new finding to notice are given preference. Methodological limitations and contradictions with the data of other studies are pointed out. FINDINGS: The psychodynamic meaning of suicide for a patient derives from both affective and cognitive components. Rage, hopelessness, despair, and guilt are important affective states in which young patients commit suicide. The meanings of suicide can be usefully organized around the conscious (cognitive) and unconscious meanings given to death by the suicidal patient: death as reunion, death as rebirth, death as retaliatory abandonment, death as revenge, and death as self-punishment or atonement. CONCLUSIONS: Knowledge of the psychodynamics helps to distinguish which patients with any given diagnosis are at risk for suicide. Such knowledge is essential to the psychotherapeutic treatment of the young suicidal patient. Topics for future research include the role of anxiety in suicide; the capacity to bear hopelessness, rage, and other unpleasant affects without regression; the use of particular defense mechanisms in distinguishing the risk of either suicidal or violent behavior; and the relation of specific psychodynamic conflicts seen in suicidal patients to particular psychiatric diagnoses. PMID- 1882992 TI - Psychosis and physical aggression in probable Alzheimer's disease. AB - OBJECTIVE: The purpose of this study was to determine the frequency and type of psychotic symptoms in patients with probable Alzheimer's disease and to test whether there is a relationship between specific psychotic symptoms and episodes of physical aggression. METHOD: From 209 patients with possible or probable Alzheimer's disease who had been assessed in a research clinic every 6 months for up to 4.5 years, 181 subjects with probable Alzheimer's disease were selected for study. On the basis of the summary note for each visit in the patients' charts, the presence of delusions, hallucinations, misidentifications, and episodes of physical aggression was determined. Data regarding psychotic symptoms and aggression were available for 170 and 169 subjects, respectively. RESULTS: Delusions had been reported for 74 (43.5%) of the patients and were the most frequent psychotic symptom; persecutory delusions were the most common type. Physical aggression had been noted for 50 (29.6%) of the patients. Delusions and misidentifications frequently preceded and were significantly associated with episodes of physical aggression. The presence of delusions was a significant predictor of physical aggression but accounted for only 3.5% of the variance. CONCLUSIONS: This study suggests that delusions are a risk factor for physical aggression in patients with probable Alzheimer's disease who have moderate to severe cognitive impairment. As delusions accounted for only a small percentage of the variance, further research is needed to identify other variables that may be significant predictors of physical aggression in this population. PMID- 1882994 TI - Are depressive symptoms nonspecific in patients with acute stroke? AB - OBJECTIVE: Some investigators have suggested that major depression might be overdiagnosed in stroke patients because of changes in appetite, sleep, or sexual interest caused by their medical illness; others have suggested that depression may be underdiagnosed in stroke patients who deny symptoms of depression because of anosognosia, neglect, or aprosody. The authors' goal was to determine how frequently depressive symptoms occur in acute stroke patients with and without depressed mood to estimate how often diagnostic errors of inclusion or exclusion may be made. METHOD: They examined the rate of autonomic and psychological symptoms of depression in 205 patients who were consecutively hospitalized for acute stroke. Eighty-five (41%) of these patients had depressed mood, and 120 (59%) had no mood disturbance. Forty-six (54%) of the 85 patients with depressed mood (22% of all patients) were assigned the DSM-III diagnosis of major depression. RESULTS: The 120 patients without mood disturbance had a mean of one autonomic symptom, but the 85 patients with depressed mood had a mean of almost four. Tightening the diagnostic criteria to account for one more nonspecific autonomic symptom decreased the number of patients with major depression by only three; adding two more criteria decreased the number by only five. Thus, the rate of DSM-III major depression was 1% higher than the rate with one extra nonspecific autonomic symptom and 2% higher than the rate with two extra criteria. Conversely, loosening diagnostic criteria to account for denial of depressive illness increased the rate of major depression by only 5%. CONCLUSIONS: Both autonomic and psychological depressive symptoms are strongly associated with depressed mood in acute stroke patients. PMID- 1882993 TI - The influence of major depression on clinical and psychometric assessment of senile dementia of the Alzheimer type. AB - OBJECTIVE: The performance on standard clinical and psychometric assessments of eight elderly individuals with major unipolar depression alone and seven with depression plus mild senile dementia of the Alzheimer type was compared with that of 41 nondepressed subjects suffering from very mild senile dementia of the Alzheimer type, 66 with mild senile dementia of the Alzheimer type, and 83 age matched subjects without senile dementia. METHOD: Subjects with depression alone, depression plus mild senile dementia of the Alzheimer type, and very mild and mild senile dementia of the Alzheimer type met strict inclusionary and exclusionary criteria. A 90-minute semistructured interview, including several brief standardized clinical scales, was used to assign a Clinical Dementia Rating to each subject according to published guidelines, and each subject was given a 2 hour psychometric test battery. Data were analyzed by one-way multivariate analysis of variance to ascertain if there was an effect of group on clinical and psychometric test scores. RESULTS: The eight depressed subjects without concurrent dementia performed as well as the 83 nondepressed subjects without dementia on most clinical measures; however, their performance on most psychometric measures closely resembled that of the 41 nondepressed subjects with very mild dementia. The performance of the seven subjects with depression plus mild dementia was comparable to that of the 66 nondepressed subjects with mild dementia on most clinical and psychometric measures. CONCLUSIONS: Although depressed subjects performed as well as subjects without dementia on many clinical assessments, psychometric testing was not able to distinguish depressed subjects from those with very mild senile dementia of the Alzheimer type. This demonstrates the need for careful psychiatric evaluation before interpreting deficits on psychometric tests as indicating the presence of very mild senile dementia of the Alzheimer type. PMID- 1882996 TI - Social competence and positive and negative symptoms: a longitudinal study of children and adolescents at risk for schizophrenia and affective disorder. AB - OBJECTIVE: The authors longitudinally examined social competence and positive and negative symptoms in children at risk for schizophrenia, children at risk for affective disorder, and matched normal subjects. METHOD: The subjects were offspring of parents with schizophrenia or affective disorder and normal comparison subjects matched on age, sex, and socioeconomic status. Ratings of social competence (Premorbid Adjustment Scale), affective flattening and poverty of speech (Scale for the Assessment of Negative Symptoms), and positive formal thought disorder (Scale for the Assessment of Positive Symptoms) were based on videotaped psychiatric interviews conducted in childhood (N = 144), early adolescence (N = 127), and adolescence (N = 106). RESULTS: In childhood, there were no significant group differences. In early adolescence, the subjects at risk for schizophrenia had poorer social competence than those at risk for affective disorder and the normal subjects. In early adolescence, the subjects at risk for schizophrenia also had greater positive thought disorder than those at risk for affective disorder but did not differ significantly from the normal subjects; there were no differences in negative symptoms. In adolescence, the subjects at risk for schizophrenia had poorer social competence and greater positive and negative symptoms than the adolescents at risk for affective disorder and the normal subjects. CONCLUSIONS: During early adolescence and adolescence, poor social competence may be more characteristic of children at risk for schizophrenia than those at risk for affective disorder. Higher levels of positive and negative symptoms may also be specific to subjects at risk for schizophrenia, but only during adolescence. PMID- 1882995 TI - Hypersomnia in bipolar depression: a comparison with narcolepsy using the multiple sleep latency test. AB - OBJECTIVE: This study characterized objectively the hypersomnia frequently seen in the depressed phase of bipolar affective disorder. On the basis of previous work in sleep and affective disorders, it has been hypothesized that the hypersomnia is related to greater REM sleep. This hypothesis was tested by using a multiple sleep latency test to compare bipolar affective disorder with narcolepsy, a well-defined primary sleep disorder associated with known REM sleep dysfunction. METHOD: Twenty-five bipolar depressed patients were selected on the basis of complaints of hypersomnia. They underwent 2 nights of polysomnography followed by a multiple sleep latency test. Data on their nocturnal sleep and daytime naps were compared with similar data on 23 nondepressed narcoleptic patients referred for sleep evaluation. RESULTS: Despite their complaints of hypersomnia, no abnormalities were noted for the bipolar group in the results from the multiple sleep latency test. Contrary to the working hypothesis, REM sleep was notably absent during daytime naps in the depressed patients, in marked contrast to the findings for the narcoleptic group. CONCLUSIONS: The complaint of sleepiness in the hypersomnic bipolar depressed patient appears to be related to the lack of interest, withdrawal, decreased energy, or psychomotor retardation inherent in the anergic depressed condition, rather than an increase in true sleep propensity or REM sleep propensity. PMID- 1882997 TI - Panic disorder and suicidal ideation and behavior: discrepant findings in psychiatric outpatients. AB - OBJECTIVE: Previous investigators found that persons who had ever met criteria for panic disorder or panic attacks reported more lifetime suicide attempts and ideation than persons who had ever met criteria for other psychiatric disorders. To determine whether outpatients with current panic disorders also report such differences, this study examined the suicide attempt rates, levels of suicidal ideation, and levels of hopelessness among four groups of psychiatric outpatients. METHOD: Structured clinical interviews were used to assign diagnoses to 900 consecutive psychiatric outpatients. These patients were administered the Scale for Suicide Ideation and the Beck Hopelessness Scale and were also questioned in detail about previous suicide attempts and past and present suicidal ideation. RESULTS: None (0.0%) of the 73 patients with primary panic disorder without agoraphobia reported having made suicide attempts during their lifetimes. One (1.3%) of the 78 patients who had panic disorder with agoraphobia, 34 (7.0%) of the 485 patients who had mood disorders, and four (1.5%) of the 264 patients who had other psychiatric disorders reported suicide attempts. The mean scores on the Scale for Suicide Ideation and the Beck Hopelessness Scale of the patients with panic disorders and other disorders were significantly lower than the mean scores of the patients with mood disorders. CONCLUSIONS: The rates of suicidal ideation and behavior for psychiatric outpatients who had panic disorders were discrepant with those reported by the earlier group of investigators for a random community sample of persons who reported ever having had panic attacks or met criteria for panic disorders. PMID- 1882998 TI - Mass hysteria among student performers: social relationship as a symptom predictor. AB - OBJECTIVE: In April 1989 an outbreak of illness suddenly afflicted student performers in Santa Monica, Calif., and an extensive investigation revealed no environmental cause. To clarify the details of the epidemic and determine whether mass hysteria occurred, the authors examined physical, psychological, and social factors that might have contributed to the outbreak. METHOD: Participating middle and high-school performers were surveyed; 93% (N = 519) responded; cases were defined as students who had one or more symptoms during the outbreak. A stepwise logistic regression analysis was used to determine significant predictors of illness. RESULTS: Characteristic features of mass hysteria were present, including preponderance of illness in girls, symptom transmission by sight or sound, presence of hyperventilation, and evidence of psychological or physical stress. Symptomatic and asymptomatic groups differed in frequency of several physical and psychological variables, but observing a friend become sick was the best predictor of the development of symptoms. CONCLUSIONS: These results confirm earlier research demonstrating multiple psychological and physical factors that contribute to such outbreaks, particularly symptom transmission through social networks. Investigators should explore social transmission as an additional characteristic feature of mass hysteria in order to facilitate early identification of future outbreaks. PMID- 1882999 TI - Long-term outcome of antidepressant treatment for bulimia nervosa. AB - OBJECTIVE: The purpose of this study was 1) to replicate previous work indicating that antidepressant medication is superior to placebo in the treatment of bulimia nervosa and 2) to assess the long-term efficacy of this form of treatment. METHOD: Eighty patients entered a three-phase treatment protocol. An 8-week double-blind initiation phase was used to compare the effects of desipramine and placebo. Patients who responded satisfactorily to desipramine entered a 16-week maintenance phase. Patients who remained well were then randomly assigned to either desipramine or placebo for 6 additional months (discontinuation phase). The primary outcome measure was binge frequency, which was assessed weekly by self-report diaries. RESULTS: In the initiation phase the superiority of desipramine over placebo in reducing binge frequency was demonstrated. Patients treated with desipramine had a mean reduction in binge frequency of 47% at termination, whereas patients taking placebo experienced a mean increase of 7%. Less than half of the patients treated with desipramine met the criteria for entering the maintenance phase, and 29% of the patients entering that phase relapsed in the following 4 months. There were not enough patients in the discontinuation phase to permit clear conclusions about the need for continued antidepressant medication after 6 months of treatment. CONCLUSIONS: The study documents a beneficial effect of desipramine in the treatment of bulimia nervosa when compared to placebo. However, limited improvement and considerable relapse with continued treatment suggest serious limitations to the long-term efficacy of a single antidepressant trial in treating bulimia nervosa. PMID- 1883000 TI - Buspirone: sedative or stimulant effect? AB - OBJECTIVE: The primary objectives of this study were to evaluate the effects of initial and continued administration of buspirone on sleep induction and maintenance and sleep stage parameters, to determine the presence or absence of any drug-induced side effects, and to ascertain the presence or absence of sleep disturbances following abrupt withdrawal of the drug. METHOD: Six insomniac subjects who had chronic complaints of difficulty falling asleep and/or staying asleep and who were in good physical health, were not suffering from any major mental disorders, and had not used any medication for at least the last month participated in a 16-night sleep laboratory protocol. The protocol consisted of 4 placebo-baseline nights, 7 nights on which buspirone, 10 mg at bedtime, was administered, and 5 placebo-withdrawal nights. RESULTS: Wake time after sleep onset increased moderately during the first 3 nights of drug administration (there was a marked and significant increase on the first night) and increased by lesser degrees with continued drug administration. Overall, reports of side effects were infrequent. Following drug termination, there was a delayed and mild increase in sleep difficulty above baseline. CONCLUSIONS: These data not only confirm that buspirone lacks sedative effects but also suggest that the drug may have stimulant properties. Further, these findings suggest that buspirone has limited usefulness in anxious patients with concomitant sleep difficulties. PMID- 1883001 TI - A behavioral approach to achieving initial cocaine abstinence. AB - OBJECTIVE: The aim of this study was to assess the efficacy of a behavioral treatment program for achieving initial cocaine abstinence in individuals enrolled in outpatient treatment for cocaine dependence. METHOD: Thirteen consecutively admitted outpatients were offered behavioral treatment consisting of contingency management procedures and the community reinforcement approach. Fifteen consecutively admitted outpatients were offered treatment with 12-step counseling. All 13 of the patients who were offered the behavioral treatment accepted it; 12 of the patients offered 12-step counseling accepted it. RESULTS: Eleven of the 13 patients in the behavioral treatment were retained for 12 weeks of treatment, compared with five of the 12 patients given 12-step counseling. Ten of the patients given behavioral therapy achieved 4 weeks of continuous cocaine abstinence, compared with only three of those given 12-step counseling. Six of the patients in the behavioral treatment group achieved 8 weeks, and three achieved 12 weeks; none of the patients in the 12-step counseling program achieved 8 weeks. CONCLUSIONS: The behavioral treatment described in this paper offers promise as an effective intervention for achieving initial cocaine abstinence. A randomized trial is underway to assess the generality of these findings. PMID- 1883002 TI - HIV seroprevalence among patients admitted to two psychiatric hospitals. AB - OBJECTIVE: The authors determined the seroprevalence of HIV-1 among patients admitted to two psychiatric hospitals in New York City. METHOD: Patients consecutively admitted to an acute psychiatric unit in Manhattan and a large state hospital in Queens were anonymously tested for HIV-1 antibodies from December 1989 through July 1990. Test results were linked to age, gender, ethnicity, and two risk behaviors: male homosexual activity and injection drug use. RESULTS: Blood was obtained from 83.0% of the eligible patients. The prevalence of HIV was 5.5% (25 of 451). Black patients accounted for 38.0% of the patients tested and 76.0% of positive results (N = 19), a rate of 11.1% for this group. The rate of seropositivity was comparable in women and men. Clinicians had charted risk behavior for nine (36.0%) of the 25 HIV-positive patients. Infection control records suggested that clinicians were aware of seven (28.0%) of the positive cases. CONCLUSIONS: One in every 18 patients admitted to two public psychiatric hospitals in New York City was HIV positive. Clinical staff largely failed to identify HIV-positive patients. Ethnicity and a history of homosexual activity among men or use of injected drugs were strongly associated with seropositivity. This pattern of infection may be linked to needle sharing and/or sexual activity with partners who have shared needles. Future research should clarify how psychiatric illness affects risk-taking behavior, focus on improving detection by clinicians, and identify effective prevention strategies in this population. PMID- 1883003 TI - Comparative phenomenology of early-onset versus late-onset panic attacks: a pilot survey. AB - Studies of panic attacks in older adults are virtually nonexistent. The authors surveyed 520 adults with panic attacks; 445 were younger than age 55, 57 were 55 years old or older but had their first panic attack before age 55, and 18 were 55 years old or older and had their first panic attack at age 55 or later. The respondents with late-onset panic attacks reported fewer symptoms during their attacks and were less avoidant than both groups of respondents with early-onset panic attacks. PMID- 1883004 TI - Serum nortriptyline levels in nursing mothers and their infants. AB - The nortriptyline levels of seven depressed mothers and their breast-fed infants were obtained. Nortriptyline was not detected in the infants' sera. However, two of four infants evaluated developed low concentrations of 10 hydroxynortriptyline. No adverse effects were observed. PMID- 1883005 TI - Episode sequence in bipolar disorder and response to lithium treatment. PMID- 1883006 TI - Elevated medial-frontal cerebral blood flow in obsessive-compulsive patients: a SPECT study. AB - Regional cerebral blood flow was measured with single photon emission computed tomography in 10 obsessive-compulsive patients and eight comparison subjects. The patients had a significantly higher ratio of medial-frontal to whole cortex blood flow; this was unrelated to symptom severity but was correlated negatively with anxiety. No differences in orbital-frontal blood flow were found. PMID- 1883007 TI - Effects of fluoxetine on regional cerebral blood flow in obsessive-compulsive patients. AB - Six drug-free obsessive-compulsive patients were given single photon emission computerized tomography scans before and during treatment with fluoxetine. The treatment significantly reduced the patients' "hyperfrontality," as determined by the ratio between medial-frontal and whole cerebral cortex blood flow, and significantly lowered ratings of obsessive-compulsive and anxiety symptoms. PMID- 1883009 TI - Appearance of obsessive-compulsive symptoms in depressed patients treated with fluoxetine. PMID- 1883008 TI - Plasma homovanillic acid in schizotypal personality disorder. AB - Schizotypal patients were found to have a significantly higher mean plasma HVA concentration than normal comparison subjects. Furthermore, plasma HVA concentration positively correlated with "psychotic-like" schizotypal symptoms. These results implicate dopaminergic mechanisms modulating the psychotic-like symptoms of schizotypal personality disorder. PMID- 1883010 TI - Extrapyramidal symptoms upon discontinuation of fluoxetine. PMID- 1883011 TI - Seizures during clozapine therapy. PMID- 1883013 TI - Retinopathy and bright light therapy. PMID- 1883012 TI - Severe immune thrombocytopenia induced by neuroleptics. PMID- 1883014 TI - Family histories of bulimic women with and without comorbid alcohol abuse or dependence. PMID- 1883015 TI - Methadone dose for cocaine abuse. PMID- 1883017 TI - Smoke-free hospital environments in 1848. PMID- 1883016 TI - Tranylcypromine abuse. PMID- 1883018 TI - Pilot program of treatment for PTSD. PMID- 1883019 TI - Carbamazepine, lithium, and life course of bipolar affective disorder. PMID- 1883020 TI - Cardiac transplantation and depression. PMID- 1883022 TI - Rapid cycling in a patient with bipolar mood disorder secondary to Graves' disease. PMID- 1883021 TI - Capgras' syndrome in a blind patient. PMID- 1883023 TI - The judges don't want to do it either. PMID- 1883024 TI - Holding the center: the medical implications of the Cruzan decision. PMID- 1883026 TI - Dissociative experiences and eating disorders. PMID- 1883028 TI - Erotomania. PMID- 1883025 TI - Meaning of the term "bulimia". PMID- 1883027 TI - Negative symptoms in schizophrenia. PMID- 1883029 TI - Combat and masculinity. PMID- 1883030 TI - Classification of koro. PMID- 1883032 TI - Position statement on HIV and youth. PMID- 1883031 TI - Comments on report on DSM-IV. PMID- 1883033 TI - [Psychiatric disorders in resuscitation units]. AB - Psychiatric disorders are observable in Intensive Care Unit. They belong to all the psychiatric field. Their genesis depend on various factors that often work together and are interdependent: organic, demographic, psychological, environmental, procedural, hypnic. They can be considered as risk factors influencing the development of responses to stress (theory of stress). PMID- 1883034 TI - [Malignant hyperthermia: halothane kinetics in a study model of muscular contraction. Head space determination and comparison with a mathematical model]. AB - Testing in vitro are used to locate malignant hyperthemia susceptible subjects. They use muscular contraction in response to anesthetic administration, particularly Halothane. They allow to classify subjects in three classes: susceptible, non susceptible and intermediate. Halothane was dosed by chromatography in the three compartments of a bath for isolated organs with a muscular fiber during steady concentrations were given and after wash out. Partition coefficient were determinated and compared to a calculated model. They are variable with physical conditions of the circuit. This results confirmed published data and give some possibilities to improve such tests to ascertain the subjects susceptibility to Halothane. PMID- 1883035 TI - Effect of psychological stress on gastric potential difference in man. AB - This study investigated the effect of three different mental stress tests on gastric transmucosal electric potential difference (GPD). GPD measurement was carried out in six healthy volunteers using the agar-KCl bridges method during dichotomous listening, the ringing of a telephone and 90 dB noise. Cardiac, pulmonary and psychological responses to stress were evaluated at the same time. During the stress period, two of the subjects had no change in GPD as well as no extragastric modification due to the stressor. The four other volunteers had a significant stress-induced fall in GPD (12.5 + 5.6 mV) with a simultaneous acceleration of heart and respiration rates and an increase in systolic blood pressure and anxiety feelings which were evaluated on a visual scale. Such mental stress, possibly mediated by autonomous nervous system, may cause some gastric mucosa changes inducing the retrodiffusion of H+ ions and a fall in GPD. This model could be useful in therapeutic research into the prevention and treatment of stress-induced gastric lesions. PMID- 1883036 TI - [Changes in posture induced by 2 osteopathic manipulations are coherent with the sagittal or frontal orientation they involve]. AB - The effects of two osteopathic handlings were studied by two stabilometric criteria: the Cervical Symetry Quotient and the Spectrum of Amplitude. Out of 60 people, half were subjected to a High Velocity Technique the force of which was located in a frontal (left-right) plane of the body, the other half to a Fascial Technique the force of which was in the saggital (antero-posterior) plane of the body. The High Velocity Technique induces a significative modification of the Cervical Symetry Quotient which tends to be normal two days later; the Fascial Technique does not modify this criterium 20 min nor 7 days later. Both techniques modify significantly the Spectrum of Amplitude, High Velocity Technique in the 0.16-0.22 Hz band and in the frontal (left-right) plane, the Fascial Technique in the 0.3 Hz band and in the saggital (antero-posterior) plane of the body. These modifications last for up to 2 and 7 days respectively. So each of these two osteopathic techniques induce postural effects in the concerned plane of the body and not (or little) in the perpendicular plane. PMID- 1883038 TI - [For or against human freedom? 3 authors, 2 theses and a behavior]. AB - Three answers to the paradox of a free mind in a determinist universe. For Amselek the paradox does not exist for the determinism is not objective but construction of human brain. Laplane think we have to replace the axioms with others compatible at once with the macrophysical determinism and the free will and postulates a reality with three faces: matter, energy mind. Laborit denies also the paradox but the three behave in every day life as free answerable people. Freedom does not exist, its appearance is the result of the multiplicity of the determinisms. PMID- 1883037 TI - [Severe chloroquine poisoning. Favourable outcome with diazepam therapy. A toxicokinetic study]. AB - A severe chloroquine poisoning, featuring indicators of bad prognosis, has been treated by a diazepam-type therapy. The outcome was favourable in a dramatic way. A toxicokinetic study showed very high chloroquine plasmatic levels, consistent with the severity of the poisoning. PMID- 1883039 TI - [The HELLP syndrome--one hypothesis]. AB - On the basis of current literary data the author presents clinical, laboratory and histomorphological parameters, which show that HELLP syndrome and acute fatty dystrophy of liver during pregnancy have equal clinical picture, equal laboratory results, equal clinical management, equal therapeutic treatment, equal early and late prognosis for the mother and fetus (infant). The indicated up to now "specific" histological finding in the liver during fatty dystrophy of the liver of pregnant women is not sufficient foundation for division of these syndromes, because it is found in the HELLP syndrome as well, because fatty vacuoles depositions in the kidneys are discovered in (grave) preeclampsia. The author concludes that the acute fatty dystrophy during pregnancy is a manifestation, a form of HELLP syndrome, but not a disease, a syndrome sui generis. PMID- 1883040 TI - [Our experience with 151 cases of abdominal extraperitoneal section in the Obstetrics-Gynecology Department of the Municipal Main Hospital in Ruse]. AB - The authors describe their experience in abdominal extraperitoneal section of 151 women. 37,986 deliveries occurred at the OG complex in the town of Ruse for the period of 1975-1985. 1,853 women (4.87%) delivered by cesarean section. 151 out of 1853 women delivered by cesarean section, using the method of Morozov. Indications on the side of the mother were found in 98 women (64.90%): protracted labour, weak and nonproductive labour activity with outpoured amniotic fluid accompanied by febrile states and signs for starting or present intrapartum infection, proven by laboratory parameters. Indications on the side of the mother and fetus were found in 53 women (35.09%) without signs of intrapartum infections. The results are very good. The operated women recover more quickly during the postoperative period. No venous administrations are needed, since women take orally fluids and food without limitations. The authors conclude that the abdominal extraperitoneal section presents greater advantages for the patient during the postoperative period. They do not think that it should be used as a routine method. It is more complex and has more requirements than the classical cesarean section. The abdominal extraperitoneal section has its place in the obstetric practice in women with intrapartum infection. PMID- 1883041 TI - [Obstetrical surgical deliveries and perinatal infant mortality]. PMID- 1883042 TI - [Our experience in the surgical treatment of stress incontinence in women]. AB - The authors present the results from 12 operations, performed by the method of Hirsch and 15 operations by the method of Pereyra--a modification of Atanasov, in patients suffering from mean and grave degree of urinary stress incontinence. Combined operations--with colpoperineoraphies and total hysterectomies were made, when indications were present. The experience showed that the postoperative period in all patients had a smooth course without data for superposed urinary infection. The spontaneous miction recovered from the 7th to 19th day. No relapses of the disease were found up to two years after the operation. PMID- 1883043 TI - [A trial of immunological correction in patients with frequently recurring chronic inflammatory gynecological diseases]. AB - Various immunomodulating drugs: levamizol in suppression of CMI and phagocytosis, gamma A in deficit of antibody synthesis and vitamins A, E, C, in patients with suppression of all immunological parameters, were added to the complex treatment of 67 patients with frequently relapsing inflammatory gynecological diseases and data for suppression of various components of the immune response. Inclusion of immunomodulators to the complex therapy induces a definite antirelapsing effect. Levamizol was of the highest clinical efficiency, presenting a definite antirelapsing effect of 66.67% of the patients, treated and observed for a period of a year. PMID- 1883044 TI - [4 cases of botryoid sarcoma]. AB - The authors describe the rare botryoid sarcoma--histomorphology, clinic, diagnosis, treatment and prognosis with a contribution of 4 own cases at the age up to 18 years. They indicate the difficulties in the establishment of the diagnosis-early clinical and histological-in three of the cases the histological examination did not establish immediately the exact diagnosis--the material was considered as "granulation tissue" or "fibroma mole". The results of the treatment are summarized as well as the choice of therapeutic methods and drugs. The applied therapeutic scheme consists of radical hysterectomy with systemic pelvic lymph dissection and postoperative chemotherapy. The described four cases are alive at the present moment and without data for tumourous relapse- respectively 11 years and 2 months, 3 years and 4 months, 2 years and 8 months after establishment of the diagnosis. PMID- 1883045 TI - [The conservative treatment of carcinoma in situ of the cervix uteri by the local application of 5-fluorouracil]. AB - Local treatment with 5% of 5-Fluorouracil (5-Fu) in the form of globules was carried out on 37 patients with carcinoma in situ of the uterine cervix, established histologically, as the application was performed once daily for a period of 14-20 days. There was a complete correlation between the cytological investigation after the conservative treatment and the histological examination of the operative material from the conization, which was made within 1-2 weeks after local application of 5-Fu. It could be possible to use cytology for objective determination of the therapeutic effect as well as a possible usage of colposcopic-directed biopsy. The conservative treatment with 5-Fu should be the first stage of treatment of these patients, but in the absence of therapeutic effect conization of the uterine cervix should be made, which reduces the risk of spontaneous abortion. The conservative treatment with local application of 5% of 5-Fu is recommended in young women, with not large lesions of carcinoma in situ of the uterine cervix and still at their reproductive age. PMID- 1883046 TI - [Our experience with the use of the new Bulgarian intrauterine contraceptive device, the Venus Cu 300 (preliminary report)]. AB - A team of the family planning centre at the Research Institute of Obstetrics and Gynecology carried out a trial on a new Bulgarian intrauterine contraceptive device (ICD), produced by the firm Venus in the town of Varna: Venus Cu 300. This is a T-shaped device with horizontal arm of 30 mm, vertical arm of 34 mm, a copper thread with an area of 300 mm2 and two control threads. It is produced from PVC. Purity of copper is over 99.9% in the copper thread. The construction of Venus Cu 300 has the positive properties of other intrauterine contraceptive devices, used in our country during the last 15 years. 87 women have been followed in 320 cycles for a period of 6 months. A larger part of them are parous, mainly with one or two children. Venus Cu 300 has been used in seven nulliparas, presenting risk for frequent abortions. Three Venus Cu 300 have been placed immediately after abortion. No pregnancy occurs, which is explained by the careful choice of the patients. Extraction of ICD has been made only in one case due to medical causes: bleeding and pain. More abundant menstruation after ICD has been found in 11.5% of women, but there has been no need to extract ICD. Inferences are made that Venus Cu 300 is in every way equal to the known models of ICD, that the trial should include a larger group of women to accumulate data in dynamics, in order to improve Venus Cu 300 eventually. PMID- 1883047 TI - [The combined treatment of male infertility in patients with idiopathic varicocele]. AB - The author reports on 1066 patients with idiopathic varicocele and fertility disturbances, in whom surgical intervention was made by the method of Ivanissevich--a high resection of the internal testicular vena. Stimulating hormonal therapy of spermatogenesis with gonadotropic preparation Pregnyl was used according to a scheme in 246 patients, nonaffected by surgical treatment with a number of spermatozoa under 40 millions/cm3. Improvement of spermatozoa parameters was found in 31.70% of the operated patients; pregnancies of their wives occurred in 15.85% of the examined men. PMID- 1883048 TI - [Obstetrical coagulopathies--current understandings]. PMID- 1883049 TI - [The pregnancy at risk and the HELLP syndrome]. PMID- 1883050 TI - [Obstetrical prognosis by x-ray pelvimetry]. AB - For a period of 44 months 87 deliveries were analyzed by roentgenological pelvimetry, performed by a method, improved by the authors (1982). The relative part of pregnant women with roentgenological pelvimetry was 1.1%. Coefficients of obstetric prognosis were defined in groups retrospectively on the basis of a large material with roentgenological pelvimetry: "compatibility", "conditioned compatibility" and "noncompatibility" as a result of the ratio of the sum of pelvic diameters to the biparietal diameter of the fetus. In the group of "compatibility" of the fetus with the bony pelvis the women, who delivered operatively, had reduced pelvic dimensions with over 0.5 sm in vertex presentations and over 0.3 sm in breech presentations as well as larger weight of the fetus (respectively 4000 and 3500 g). The obstetric prognosis of the groups "compatibility" and "noncompatibility" was exact in 88.9% of the vertex presentations and in 81.5% of the breech presentations. PMID- 1883051 TI - [Antenatal diagnosis in cases of renal agenesis]. AB - Renal agenesia was established by antenatal ultrasound diagnosis in 3 cases. The ultrasound image is characterized by the impossibility to visualize one or both fetal kidneys, oligohydramnios, lung hypoplasia and hypotrophy of the fetus. The possibilities for the earliest diagnosis as well as for interruption of pregnancy on account of the lethal outcome of the disease in the newborn are discussed. PMID- 1883052 TI - [A rare finding of a congenital anomaly of the reproductive organs in a woman]. PMID- 1883053 TI - [The treatment of vaginal candidiasis with a single oral dose of fluconazole]. AB - Fluconazole is a new oral absorbing triazolic antimycotic, inhibiting specifically the sterol synthesis of fungal membrane. Treatment with a single dose of 150 mg of fluconazole was carried out on 33 nonpregnant women with clinical and microbiological data for vaginal candidiasis. The high percentage of recovered patients, good tolerance to the preparation as well as easy scheme for usage gives ground to be recommended for wide gynecological practice. PMID- 1883054 TI - [The use of Solcoderm in acute condylomas of the vulva (preliminary report)]. AB - A preliminary study was carried out on women with acute condylomas, treated with the preparation solkoderm. Preliminary data from the clinical trial show that the preparation should be used in some women with acute condylomas of the vulva after available clinical evaluation. PMID- 1883055 TI - [The treatment and prevention of premenopausal uterine hemorrhages with Trisequens]. AB - The authors describe the results from 30 women with premenopausal uterine bleedings and accompanying neuro-autonomic climacteric symptoms, treated with the combined estrogestagenic preparation (Trisequens--Novo Nordisk A/S). The mean age of the contingent is 47.64 years. The clinical characteristics of pseudomenstrual function, climacteric symptoms, fatty metabolism and carbohydrate tolerance are examined. Stable pseudomenstrual function, discontinued or sharply reduced climacteric symptoms, lack of substantial changes in the fatty and carbohydrate metabolism are found after treatment. It is necessary that similar treatment could be used considerably more widely in the daily gynecological practice. PMID- 1883056 TI - [A clinical trial of the preparation hypnomidate in gynecological operations]. AB - The influence of the venous anaesthetic hypnomidate (Yansen, Belgium), used as an induction anaesthetic, was studied on some parameters of respiration, hemodynamics, acid-base balance. The authors are of the opinion that the preparation is suitable for induction in anaesthesia especially in patients with high risk. PMID- 1883057 TI - Withdrawal of levorphanol. PMID- 1883059 TI - [The evolution of carboxyhemoglobin during long-term closed-circuit anesthesia]. AB - In 40 patients who underwent protracted orthodontic operations, the accumulation of carboxyhemoglobin (COHb) in the blood was studied. Mechanical ventilation during anesthesia was carried out in a closed system (group I, n = 20). Patients in a control group received mechanical ventilation with a constant fresh gas flow of 6 l/min (group II, n = 20). During closed-system ventilation, a constant rise of COHb was observed. Smokers had much higher COHb values than nonsmokers at the beginning of and during anesthesia. The relative increase of COHb in a defined time period was of the same magnitude for smokers and nonsmokers. Critical values for carbon monoxide (CO) intoxication were not measured. The mean rise was 0.05 g/100 ml COHb over 6 h. Two female patients had COHb rises of 0.29 g/100 ml and 0.18 g/100 ml over the same period. During ventilation with a high flow of fresh gas, the COHb level decreased in all patients. In nonsmokers, the value approached the physiological range of 0.4% to 0.8% COHb. A marked fall of COHb could also be observed in smokers; however, normal physiological values were not reached. Patients with low COHb tolerance (anemia, severe coronary heart disease, peripheral vascular disease) or with increased endogenous CO production (pregnancy, newborns, hemolytic disease, porphyria cutanea) should not undergo protracted ventilation in a closed circle system. PMID- 1883058 TI - [Complication-free early extubation following abdomino-thoracic esophagectomy]. AB - The combined thoracoabdominal procedure for patients with esophageal cancer is still associated with a high rate of pulmonary complications. Many institutions believe prophylactic postoperative mechanical ventilation to be the most effective measure against pulmonary complications. On the other hand, the duration of mechanical ventilation can have a significant influence on the incidence of pulmonary complications, which are increased after prolonged ventilatory support. Interstitial pulmonary edema is a frequent pathological finding with a poor prognosis after esophageal surgery. Increased water retention in the lung means a greater risk of atelectasis or pneumonia. At the St. Clara Hospital, Basle, patients with esophagectomy were extubated on the day of surgery. Despite early extubation there was a very low rate of minor pulmonary complications. To clarify possible factors contributing to this uncomplicated postoperative course, 20 patients with thoracoabdominal resection of the esophagus were evaluated. All patients were operated upon using a combination of thoracic epidural and light general anesthesia. At the end of the operation all were breathing spontaneously. After a short period of pressure support ventilation and continuous positive airway pressure (CPAP), the mean extubation time was 3 h 10 min postoperatively. Local anesthetics and morphine given by the epidural route and the simultaneous use of nonsteroidal anti-inflammatory drugs made possible an uneventful and pain-free postoperative course. Early extubation, the immediate use of a CPAP mask system 2-3-hourly and an effective cough were the main points of respiratory therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883060 TI - [Pollution of the workplace by anesthetic gases. Causes and prevention]. AB - Waste anesthetic gas concentrations were measured in areas corresponding to the breathing zones of the anesthetists and operating room nurses for personal exposure (n = 27, time-weighted values) and during special work practices (n = 65). Leaks related to anesthetic machines and high-pressure nitrous oxide components were investigated during (n = 60) and after anesthesia (n = 85). The effect of a local scavenging system on occupational exposure during inhalation induction of anesthesia in children was studied (n = 60). Concentrations of nitrous oxide, halothane, isoflurane, and enflurane were determined by using active dosimeters (SKC 222) and different infrared gas-analyzers. Factors that increase waste anesthetic gas concentrations in operating rooms can be divided into several categories, such as low air conditioning systems, anesthetists' work practices, equipment leakage, including leakage from high-pressure nitrous oxide systems, and inadequate scavenging devices. Equipment leakage is almost invariably present in low-pressure components of the anesthesia machine because so many seals and joints are necessary to permit disassembly for cleaning and replacement. Waste anesthetic gases are also distributed in the exhaled air of patients recovering from anesthesia. To restrict the levels, exposure must be as low as can be achieved with reasonable efforts. Thus, the anesthetic equipment should be designed to avoid leakage, leakage tests should be performed before the use of anesthetic machines, and waste anesthetic gases should be scavenged by central as well as by local systems. Regular and periodic use of a trace gas analyzer permits direct observation of gas leakage and enables anesthetists to modify their work technique in order to reduce avoidable leakage. PMID- 1883061 TI - [Secondary penetration of a ventriculo-peritoneal shunt into the intestines. Possible cause of a recurring sepsis?]. AB - We present a 28-year-old-patient with a severe head injury: skull fractures, epidural hematoma, subarachnoid hemorrhage, Glasgow coma score 7, and aspiration following a motorbike accident. A systemic infection with symptoms of shock and Staphylococcus aureus in blood culture specimens developed a few days after admission (later Staphylococcus epidermidis was also cultured). A posttraumatic hydrocephalus was treated by a ventriculo-peritoneal shunt inserted at mini laparotomy. In multiple microbiological and cytological tests the cerebrospinal fluid (CSF) was always sterile. Enterocolitis occurred with Clostridium difficile and Staphylococcus aureus in stool cultures. After 6 months' intractable sepsis the patient died with multiple-system failure. Autopsy revealed secondary displacement of the shunt catheter into the intestinal lumen. A possible ascending infection was found in the form of a cerebral ventricular empyema. However, prior to death there was no specific clinical sign of peritonitis or encephalitis or a positive microbiological or cytological CSF findings. Despite insertion of a ventriculo-peritoneal shunt under visual control, this case shows that secondary displacement of the peritoneal extremity into the bowel can occur, which may cause a cerebral and eventually a systemic infection. CSF examinations may fail to show contamination; specific clinical signs may be absent or, with multiple-system failure, misleading. An autopsy is generally to be recommended as it contributes to a better understanding of the clinical problems in most cases. PMID- 1883062 TI - [A computerized database for problem patients in pediatric anesthesia]. AB - A computerized database for use in pediatric anesthesia and in the perioperative care of patients with malformation syndromes and rare diseases is presented. A total of 2200 syndromes are listed, and the database contains helpful data, experience, guidelines and literature references relevant to about 500 rare diseases. The access to the databank, its structure and the probable benefits of the system are explained and discussed. PMID- 1883063 TI - [An adapter for the intratracheal application of a bronchodilator to intubated patients]. PMID- 1883064 TI - [A cost comparison of PALL filters versus chemical or thermal disinfection of ventilator tubes]. PMID- 1883065 TI - [Verification of the position of the tube: reliable "unreliable" methods and recent developments]. PMID- 1883066 TI - [Hemodynamics and myocardial energy balance in coronary surgery patients during high dose fentanyl-pancuronium anesthesia and modified neuroleptic-pancuronium anesthesia]. PMID- 1883068 TI - Four-sector tandem mass spectrometric analysis of complex mixtures of phosphatidylcholines present in a human immunodeficiency virus preparation. AB - A number of phosphatidylcholines have been isolated from an HIV-1/MN preparation by reversed-phase high-performance liquid chromatography (HPLC) and analyzed by fast atom bombardment mass spectrometry (FABMS), FABMS/MS, and FABMS/MS/MS in both positive- and negative-ion modes. Negative-ion FABMS/MS with high-energy collisions was used to identify the length of the acyl groups and the degree of saturation, as well as their position on the glyceride group. FABMS/MS in the positive-ion mode was used to identify the polar head group. Negative-ion FABMS/MS/MS was used to locate positions of double bonds in acyl groups. We find that four-sector tandem mass spectrometry with high-energy collisional activation provides qualitative analysis of viral phosphatidyl lipids in considerable detail, as well as semiquantitative information. Approximate quantitation of the phosphatidylcholine content of the HIV-1/MN preparation by measuring relative peak heights of molecular ions in FABMS reveals an array of phosphatidylcholines consistent with that found in human erythrocytes, indicating the likely source of lipids in the viral membrane to be the host cell membrane. PMID- 1883067 TI - Primary structure determination of peptides and enzymatically digested proteins using capillary liquid chromatography/mass spectrometry and rapid linked-scan techniques. AB - Primary protein sequences were determined for both peptides and enzymatically digested proteins by rapid linked-scan (B/E) liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) at the low-picomole level (10-50 pmol). During the course of a single LC/MS/MS analysis, we demonstrated that it is possible to generate interpretable collision-induced dissociation spectra of the eluting proteolytic peptides. Molecular weights of tryptic peptides were established by using 1/10 of the protein digest by operating in the capillary LC/frit-FABMS mode. Peptides exhibiting the strongest MH+ ions were then selected for subsequent LC/MS/MS analysis (typically 1/5 of the remaining protein digest). Elution times for each chromatographic peak were generally greater than 30 s. It was therefore possible to obtain a minimum of six B/E fast linked-scan spectra during the course of elution of each peptide component. Typically, B/E linked scans of the greatest ion abundance (obtained at the chromatographic peak maximum) were averaged to enhance the signal/noise ratio at these low-picomole levels. Unit resolution was observed for product ions below m/z 1000. Rapid linked scanning by LC/frit-FABMS/MS provided mass assignments for product ions within 0.2-0.3 amu of theoretical values. Side-chain fragment ions (wn and dn) were also observed, which allowed for the differentiation of isobaric amino acids (e.g., leucine and isoleucine). Examples of the application of this fast linked scan technique to LC/MS/MS are presented for complex mixtures of unknown peptides and the tryptic digestion of phosphorylated beta-casein. PMID- 1883069 TI - Process monitoring by parallel column gradient elution chromatography. AB - A system was developed that generates two gradients simultaneously, 180 degrees out of phase. Essential elements of the system were a pump delivering solvent A at a constant velocity, a pump delivering solvent B at a constant velocity, two mixing chambers, and a ten-port valve. By use of this gradient device and two reversed-phase columns packed with 1000-A pore diameter, 8-microns particle size macroporous poly-(styrene-divinylbenzene) resin, six proteins were separated in 40 s in a single gradient cycle. PMID- 1883071 TI - Determination of tin in human blood serum by radiochemical neutron activation analysis. AB - A method was developed for the determination of tin in human serum by radiochemical neutron activation analysis, using the long-lived radioisotope Sn(T1/2 = 115.09 days). This radioisotope decays to a daughter isotope 113mIn, the most suitable nuclide for counting (T1/2 = 1.658 h, gamma-ray of 391.7 keV). Experience showed that, with the exception of the serum samples with the lowest tin levels, in the experimental conditions of the present study tin could mostly also be determined by using its radioisotope 117mSn(T1/2 = 13.61 days, gamma-ray of 158.5 keV). Samples were collected and prepared by using the procedure elaborated by the authors, which proved its effectiveness in preventing significant sample contamination on several occasions. Because samples had to be irradiated at 10(14) n.cm-2.s-1, dry ashing was necessary. After irradiation, tin was separated by solvent extraction of tin(IV) iodide from a sulfuric acid ammonium iodide solution with toluene. The dry ashing and solvent extraction steps were exhaustively tested by means of radioactive tracer experiments whereas the accuracy and precision of the analytical method were thoroughly checked by analyzing biological reference materials (Bowen's kale powder, the NBS' bovine liver, the NBS' nonfat milk powder, and the "second-generation" biological reference material--freeze-dried human serum--for trace element determinations, developed by the authors).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883070 TI - Capillary electrophoretic separations of proteins using nonionic surfactant coatings. AB - Capillary zone electrophoretic separations of proteins have been achieved by using nonionic surfactant coated capillaries. Capillaries were prepared by derivatization of the silica surface with octadecylsilane followed by the deposition of a layer of nonionic surfactant from an aqueous solution above the critical micelle concentration. This coating is of sufficient thickness and hydrophilicity to reduce both protein adsorption and electroosmotic pumping. This hydrophilic coating reduces electroosmotic pumping 5-8-fold while resolving proteins quickly and efficiently with good recovery. The coating provides a stable and reproducible means of deactivation, while the rate of electroosmotic pumping stays relatively constant throughout the pH range 4-11. This allows the pH to be varied to enhance selectivity without adversely affecting the flow rate. PMID- 1883072 TI - Liquid chromatographic determination of linear alkylbenzenesulfonates in aqueous environmental samples. PMID- 1883074 TI - Scanning electron microscopy of the ovary in the house musk shrew, Suncus murinus. AB - The structure of the house musk shrew (Suncus murinus) ovary, prepared by the Osmium-DMSO-Osmium method, was examined with a scanning electron microscope. Many ovarian follicles in various stages of development can be seen in the musk shrew ovary, but fully matured follicles (Graafian follicles) are never observed. In the inner layer of zona granulosa of the preantral follicles, the follicular cells containing a large amount of glycogen deposition in the cytoplasm are observed. Folded and collapsed zona pellucida surrounding the remnant of the degenerated oocyte, which is thought to be a residual form of atretic follicle, is observed in a small, crypt-like depression on the surface of the ovary where it has been split by cracking. PMID- 1883073 TI - Monitoring groundwater and well water for crop protection chemicals. PMID- 1883075 TI - Photosensory elements in the pineal gland of the Japanese quail, with special reference to the paraboloid. AB - In 1-day-old Japanese quails, Coturnix coturnix japonica, photosensory elements of the pineal gland were examined by means of histochemical demonstration of glycogen and transmission electron microscopy. The parenchymal cells of the quail show immature structure, especially, small apical protrusion with a few mitochondria in the pinealocyte and rare appearance of the dense body in the supporting cell. The paraboloid is found in cytoplasmic processes projecting into the follicular lumen and in perikarya of the follicular cells. It is composed of a well-developed network of tubular smooth-surfaced endoplasmic reticulum and abundant glycogen granules, but there is not a higher concentration of glycogen in its central region. The paraboloid-containing cell is considered as a type of the pinealocyte, because of occasional appearance of the synaptic ribbon in its perikaryon. In addition to lamellar whorls, regular stacks of lamellar disks are observed in the pineal lumen, being adjoining to the paraboloid-containing cytoplasmic process. The present results may provide further evidence for the direct photoreception by the avian pineal. PMID- 1883077 TI - Qualitative and quantitative glial changes in the hippocampus of aged rats. AB - Ultrastructure of the glial cells in the CA 1 hippocampal field and some quantitative parameters characterizing the astrocytes in stratum lacunosum moleculare (str. L-M) of the CA 1 hippocampal field of young-mature (3-month old) and aged (24-month old) rats were examined. The qualitative observations showed structural changes in astrocytes, oligodendrocytes and microglial cells in all layers of the CA1 hippocampal field in aged rats. The quantitative analysis demonstrated a considerable increase in total and individual volume fractions of astrocyte processes, in number of astrocyte profiles per square area of neuropil and in percentage area of neuropil occupied by astrocyte process profiles. These changes as well as the increased number of astrocyte nuclei suggest the appearance of hypertrophy and hyperplasie of astrocytes in str. L-M of the CA 1 hippocampal field of rats in aging. PMID- 1883076 TI - Intrauterine development in the rat following continuous exposure to nicotine from gestational day 6 through 12. AB - Cigarette smoking during pregnancy is associated with various perinatal complications, but the range of vulnerability to the embryo has not been fully characterized. The effects, in vivo, of continuous exposure to nicotine on postimplantation embryos, were investigated in the rat. Osmotic minipumps, implanted subcutaneously, were used to deliver the nicotine (75 and 150 micrograms/hr) from gestational day 6 through 12, 14 of 16 developmental endpoints, including embryonic growth, were significantly retarded; dysmorphogenesis was not observed. The results reveal that most embryological primordial lagged significantly in their development, following exposure to nicotine during early gestation. PMID- 1883078 TI - Morphometry and classification of the cat hypothalamic capillaries using multivariate analysis. AB - Multivariate statistical methods were used to do morphological determination of the amount and the relation of the astrocytic foot processes (AF), astrocytic lamina (AL) and dense zones (DZ) on hypothalamic capillaries. We corroborated that 100% of the perivascular membrane is surrounded by glial astrocytic cytoplasm. Principal component analysis shows that the original variables are independent of one another. Cluster analysis confirms the individual situation obtained through the principal component analysis. Discriminant analysis shows that the discriminant capacity of the 3 variables is very significant. For the potential interrelations of astrocytic foot processes, astrocytic lamina and dense zones we have clearly differentiated four groups of hypothalamic capillaries. PMID- 1883079 TI - The aortic bodies of spontaneously hypertensive (SHR) and normotensive rats--a study concerning location and size. AB - The aortic bodies, including the right and left subclavian bodies and the superior aorticopulmonary bodies, were examined in inbred normotensive control rats (NCR) of the Wistar strain and in spontaneously hypertensive rats (SHR) of the OKAMOTO-AOKI strain. Paraganglia were found in all rats of either group. They were located near to the left common carotid artery and less frequently between the branching right subclavian and right common carotid artery. Superior aorticopulmonary bodies were rarely seen. No significant differences were found regarding the volume of individual aortic bodies when comparing these paraganglia in NCR and SHR. However, aortic bodies are more numerous in SHR and therefore the total volume of aortic body tissue per rat is significantly larger in this strain. There was good correlation between the total volume of aortic bodies and the total volume of carotid bodies in both strains of rats studied. These findings indicate, that the paraganglionic system as a whole is enlarged in SHR. This enlargement probably is caused genetically and not a result of increased blood pressure. PMID- 1883080 TI - Functional anatomy of the tunica muscularis in the upper human duodenum. AB - The arrangement of the muscular elements in the upper duodenum were examined. Continuity is found between some of the fiber bundles from the outer and inner layers, forming an extensive helicoidal system of bundles. Some fiber bundles from the external layer penetrate the pancreatic stroma while others are related to the tunica adventitia of the duodenum, hepato-duodenal ligament and wall of the gastroduodenal artery. PMID- 1883081 TI - American Society of Anesthesiologists. 1991 annual meeting. San Francisco, California, October 26-30. Abstracts. PMID- 1883082 TI - Effects of postmilking teat treatment on the colonization of Staphylococcus aureus on chapped teat skin. AB - Sixteen Holstein cows were used to test the effect of postmilking teat treatment on colonization and intramammary infection by Staphylococcus aureus on chapped teats. Treatments were (1) chapping the teat and using 1% I2/10% glycerin postdip solution, (2) 1% I2/10% glycerin postdip solution on nonchapped teats, (3) chapping the teat and using 10% glycerin postdip solution, (4) chapping the teat and not using a postdip solution. All mammary glands were free of S aureus teat skin colonization and intramammary infection at the start of the study. Teats selected for chapping were dipped in 1N NaOH prior to 3 applications of S aureus broth culture; cultures were applied at 12-hour intervals on all teats. Treatments were applied after each milking for 30 days and were initiated after the second broth dip. Teat skin swab specimens and milk samples were collected before treatment application. Teat skin condition was scored daily. Nonchapped teats (treatment 2) did not support skin or orifice colonization by S aureus. Treatment-1 teats healed most rapidly and supported less colonization in skin and orifice than did treatment-3 and -4 teats. Teat skin scores and skin colonization were lower for treatment-3 than treatment-4 teats. A correlation between teat skin colonization and teat skin conditions was found. Two intramammary infections were found in treatment-4 quarters and 1 in a treatment-3 quarter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883083 TI - Use of embryonating eggs for isolation of Campylobacter species from intestines of swine with proliferative enteritis. AB - Intestinal tissues from swine affected with proliferative enteritis were ground, filtered through a 0.65-micron pore membrane filter, diluted, and injected into 7 day-old embryonated hens' eggs via the yolk sac. At 2, 4, and 7 days later, yolk sac swab specimens taken from live embryos were cultured for Campylobacter species. Campylobacter hyointestinalis was recovered from eggs injected with tissues of swine with acute hemorrhagic proliferative enteritis at dilutions up to 10(-4). Campylobacter mucosalis was recovered from eggs injected with tissues of swine with chronic proliferative enteritis at dilutions up to 10(-6). Campylobacter coli was recovered from several specimens without lesions of proliferative enteritis and also from some specimens with lesions of proliferative enteritis. Two previously undescribed hemolytic Campylobacter species designed as hemolytic number 1 and hemolytic number 2 were recovered from normal and experimentally inoculated swine tissues. Few contaminating organisms grow in eggs and these were usually recovered at dilutions of 10(-2) or less. Recovery of Campylobacter species by use of these techniques was seldom successful in tissues stored at -70 C for more than 6 months. PMID- 1883084 TI - Experimental establishment of persistent infection in swine with a zoonotic strain of Salmonella newport. AB - An experiment was conducted to determine whether a persistent Salmonella newport infection could be established in swine, to determine duration of shedding and distribution of the organism in internal organs, and to determine whether changes occurred in antimicrobial susceptibility or plasmid profile of the organism during the course of long-term infection. Naturally farrowed Salmonella-free pigs (n = 22) were orally exposed to a multiply antimicrobial-resistant zoonotic strain of S newport when they were 7 weeks old. Tonsillar and rectal swab specimens were examined bacteriologically for S newport during the first week after exposure, then weekly for 7 weeks. Fecal samples were likewise examined weekly or every 2 weeks for 28 weeks after exposure. Necropsies of 2 or 3 randomly selected pigs were conducted at 2, 4, 8, 12, 16, 20, 24, and 28 weeks after exposure. A total of 45 specimens/pig representing the following internal organs or tissues were examined bacteriologically for S newport: liver, spleen, kidney, gallbladder, heart, heart blood, lung, stomach, and tonsils; segments of the intestinal tract with corresponding lymph nodes; and lymph nodes from lymphocenters of the head and neck, thoracic cavity, thoracic limbs, abdominal viscera, and abdominal wall. Exposure to S newport induced a mild and transient clinical response. The organism was recovered from 97% of tonsillar swab specimens and 89% of rectal swab specimens collected during 7 weeks after exposure and from 98% of fecal samples collected during 28 weeks after exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883085 TI - Evaluation of Campylobacter jejuni colonization of the domestic ferret intestine as a model of proliferative colitis. AB - Forty 3- to 17-week old domestic ferrets, including 2 gnotobiotes, were inoculated orally and/or rectally with 10(6) to 10(9) colony-forming units of 1 or more of 4 strains of Campylobacter jejuni, 3 of mink and 1 of human origin. Feeding or gavage of any of the 4 strains, in milk or broth, with or without preinoculation sodium bicarbonate treatment to neutralize stomach acid, induced colonization in 38/40 ferrets; diarrhea lasted 2 to 4 days in conventional kits, 6 days in gnotobiotes. Bacteremia was detected in 4 of 18 tested, 2 to 5 days after inoculation. Two strains caused no more severe disease or prolonged colonization after 3 serial IV passages in kits than they did before passage. Multiple inoculations with a given strain resulted in progressively briefer colonization and milder disease, but subsequent inoculation with a different strain induced colonization and gastrointestinal disease similar to a primary infection. Five kits inoculated rectally after 4 previous homologous inoculations were resistant to colonization as well as to disease. Agglutinin titers of ferrets inoculated orally or rectally once were low or undetectable, but increased in response to repeated inoculation. Pretreatment with a 1% formalin enema caused mild colon irritation without clinical or histologic evidence of proliferative colitis in ferrets concurrently inoculated orally and/or rectally, whether or not they had preexisting antibodies to any strain of C jejuni. Histologic examination of tissues revealed leukocytic infiltration of intestinal lamina propria in 29 of 35 infected kits and 5 of 8 noninfected controls, and cryptosporidiosis in 5 infected kits plus 1 control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883087 TI - Secretion of interleukin-1 by bovine milk macrophages. AB - The relative sensitivity of bovine blood monocytes and macrophages isolated from milk to lipopolysaccharide, with respect to interleukin 1 (IL-1) production, was evaluated. Addition of lipopolysaccharide (0 to 30 microgram/ml) to the culture medium resulted in increases in secreted and intracellular IL-1 activity for monocytes and milk macrophages, with maximal stimulation achieved at 30 micrograms of lipopolysaccharide/ml of medium. At this concentration of lipopolysaccharide, monocytes released 76% of the total IL-1, whereas milk macrophages released only 26% of the total IL-1 produced within the cell. Secretion of a small quantity of IL-1 was a common property of macrophages isolated from healthy and mastitic quarters. We concluded that limited secretion of IL-1 may render the milk macrophages less efficient in promoting lymphocyte activation. PMID- 1883086 TI - Colonization control of lactose-fermenting Salmonella typhimurium in young broiler chickens by use of dietary lactose. AB - Inclusion of lactose in the diets of chickens has been determined to reduce cecal colonization with Salmonella typhimurium. We hypothesized, therefore, that dietary lactose may be a practical means for reducing the prevalence of Salmonella contamination of chicken products. Because some strains of Salmonella are atypical and ferment lactose, we investigated the effects of dietary lactose on cecal colonization with lactose-fermenting S typhimurium. Broiler chicks were inoculated intracloacally with Lac+ S typhimurium selected for resistance to novobiocin and rifampicin. The chicks also were inoculated orally with certain anaerobes that do not effectively inhibit colonization by S typhimurium, but do appear essential for lactose mediated inhibition of cecal colonization. Control chicks were not given dietary lactose, and chicks in the experimental group were fed a diet containing 7% lactose. Enumeration of Lac+ S typhimurium in cecal contents revealed dietary lactose to be effective at controlling this organism. Control was correlated with changes in cecal pH and increases in undissociated volatile fatty acids, especially propionic acid. PMID- 1883088 TI - Enzyme-linked immunosorbent assay for detection of antibodies against Mycobacterium paratuberculosis in goats. AB - Using a heat and sonicated Mycobacterium paratuberculosis Cordoba antigen (COA1) and the commercial protoplasmic-antigen (PPA-3) as antigens, an ELISA for detecting goat antibodies was standardized. When 2 reference populations, 1 positive (17 goats) and the other negative (63 goats) to disease, were used, this test showed 87.5% sensitivity and 93.6% specificity for COA1, and 88.2 and 95.2%, respectively for PPA-3. Absorption with M phlei was performed; no significant differences were found for COA1, but a lower sensitivity was found with PPA-3. This test was not especially affected by cross-reactivity with other mycobacterial disease because when 9 goats with M bovis infection were included in the M paratuberculosis control group, the specificity was only slightly different for absorbed (94.4%) and nonabsorbed sera (91.7%) for COA1, and (93.1 and 94.4%, respectively) for PPA-3. This test was used to study the percentage of seropositive goats for M paratuberculosis in 3 herds with different prevalences. Among 251 goats in southern Spain (Huelva), 40% were found positive for COA1 and 41% for PPA-3. Among 242 goats studied in southern Spain (Cordoba), 10.0% were positive for COA1 and 13.0% for PPA-3. In the Canary Island population of 176 goats, 3% were positive for COA1 and 0.5% for PPA-3. According to the accuracies of both positive and negative predictions, our test could be applied to populations with high prevalence to prevent additions to the herd and to cull infected animals (with 40% prevalence, the positive and negative predictive values are 90%), and to prevent adding infected animals to populations with moderate or low prevalence. PMID- 1883089 TI - Phagocytosis and erythrocyte antibody-rosette formation by three populations of mononuclear phagocytes obtained from dogs treated with glucocorticoids. AB - The effect of systemic administration of glucocorticoids was evaluated on 3 populations of macrophages obtained from healthy dogs. Phagocytic and Fc-receptor activities were determined for mononuclear phagocytes from blood and pulmonary and peritoneal lavage fluids. Samples were collected from 12 dogs before treatment and again on the same dogs after glucocorticoid administration. Thirty or more days were allowed between treatment periods. Twelve hours after combined prednisolone sodium succinate and dexamethasone sodium phosphate administration, the percentage of phagocytosing cells decreased for blood monocytes and increased for pulmonary macrophages. The percentage of pulmonary macrophages positive for erythrocyte antibody-rosette formation (Fc-receptor activity) increased. After 7 days of oral administration of prednisone, the percentage of phagocytosing peritoneal macrophages increased, whereas the percentage of blood monocytes with Fc-receptor activity increased. Results indicate that significant (P less than 0.05) changes in macrophage function occur after systemic administration of the glucocorticoid doses used in this study. Also, the effect of systemic administration of glucocorticoids on mononuclear phagocytes varies, depending on the specific cell location. PMID- 1883090 TI - Frequency and severity of osteochondrosis in horses with cervical stenotic myelopathy. AB - We compared the frequency and severity of osteochondrosis lesions in young Thoroughbred horses with cervical stenotic myelopathy (CSM) vs that in clinically normal Thoroughbreds of the same age. All lesions of the cervical vertebrae and appendicular skeleton were classified histologically as osteochondrosis or nonosteochondrosis and were measured for severity. Minimal sagittal diameter was significantly smaller in horses with CSM from C2 through C6; no difference was detected at C7. Severity of cervical vertebral osteochondrosis was greater in the horses with CSM, however frequency was not different. Frequency and severity of nonosteochondrosis lesions were not different in cervical vertebrae or appendicular skeleton. Frequency and severity of appendicular skeleton osteochondrosis lesions were both greater in horses with CSM. Osteochondrosis and nonosteochondrosis lesions were more severe on facets at sites of compression than on facets at noncompressed sites in horses with CSM. However, compression was also observed at sites with no articular facet lesions. The association of widespread osteochondrosis and spinal canal narrowing with CSM suggests CSM may represent a systemic failure in the development or maturation of cartilage and bone. PMID- 1883091 TI - Effects of amiodarone on myocardial performance in normal canine hearts and canine hearts with infarcts. AB - The effects of IV administered amiodarone, a class-III antiarrhythmic agent, on myocardial contractility, early myocardial relaxation, and hemodynamic variables were evaluated in normal canine hearts and those with infarcts. In the normal canine heart, amiodarone had important, but relatively mild, depressant effects on left ventricular contractility (assessed by maximal positive first derivative of left ventricular pressure (+dP/dtmax) and maximal elastance (Emax)) and heart rate when given IV at a dose of 10 mg/kg of body weight. An effect on contractility or active relaxation (assessed by maximal negative first derivative of left ventricular pressure (-dP/dtmax) and the time constant of isovolumic pressure decrease) was not identified with smaller doses. Myocardial infarction itself caused a predictable and marked depressant effect on myocardial contractility, as indicated by decreases in +dP/dtmax, ejection fraction, Emax, and -dP/dtmax, and elevation in end diastolic pressure. Additional depressive effects on contractility and active relaxation resulted when 10 mg of amiodarone/kg was administered to dogs with myocardial infarction and these effects were sufficient to worsen acute myocardial infarction-induced heart failure. Significant changes attributable to heart rate alone could not be identified. On the basis of our findings, we suggest that amiodarone administered IV should be used with caution in dogs with compromised ventricular function. PMID- 1883092 TI - Pharmacodynamic properties of succinylcholine in greyhounds. AB - Succinylcholine is a depolarizing neuromuscular blocking drug, which is rapidly hydrolyzed by the enzyme pseudocholinesterase. In Greyhounds, the metabolism of certain drugs is atypical relative to other breeds, and it has been suggested that Greyhounds may be an atypical population, with lower pseudocholinesterase activity, slower hydrolysis of the drug succinylcholine, and a prolonged duration of action of the drug, compared with a mixed-breed control population. Six healthy adult Greyhounds and 6 healthy adult mixed-breed dogs were studied. Blood was drawn from each dog and analyzed for serum cholinesterase activity, and a biochemical profile was done to verify normal liver function. The dogs were anesthetized with methohexital (10 mg/kg) and isoflurane (1.25 minimal alveolar concentration) in 100% oxygen. Ventilation was controlled, fluids were administered IV (lactated Ringer solution, 10 ml/kg/h), and blood gases, blood pressure, and heart rate were monitored. The right hind limb was immobilized and a force transducer was used to monitor twitch strength of the interosseous muscle with supramaximal stimulation of the tibial nerve. Succinylcholine was administered to each dog 3 times at a dosage of 0.3 mg/kg. After drug administration, the time to 50% recovery of twitch strength (single twitch, 1/s), and 50% recovery of train-of-4 was determined. Subsequent doses were administered after complete recovery. The time to 50% recovery after succinylcholine administration in Greyhounds (38 minutes, dose 1, single twitch) was not significantly different than the time to 50% recovery in mixed-breed dogs (29 minutes, dose 1, single twitch), using either monitoring technique. Pseudocholinesterase activity was also not significantly different between the Greyhounds (1,685 mU/ml) and the mixed-breed dogs (1,588 mU/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883093 TI - Serum glucose and insulin responses to an insulin-containing ophthalmic solution administered topically in clinically normal cats. AB - Serum glucose and immunoreactive insulin concentrations were monitored after topical administration of an insulin-containing ophthalmic solution in 20 clinically normal cats. Three ophthalmic surface-acting agents, benzalkonium chloride, dimethyl sulfoxide, and proparacaine hydrochloride, were evaluated individually for their effectiveness in enhancing absorption of topically applied insulin. The ophthalmic effects of insulin-containing ophthalmic preparations were assessed by complete ophthalmic examination before and at the conclusion of each test period. Withholding of food overnight (12 hours) preceded each topical application of insulin-containing ophthalmic solution (12.25 to 26.4 U/cat), either alone or in combination with surface-acting agents, after which blood samples were drawn serially from an indwelling IV catheter over a period of 8 hours. Baseline serum insulin concentration, after food was withheld for 12 hours, in nonstressed cats was 6.0 microU/ml (geometric mean), and an exponentiation of the logarithmic quantity (mean +/- SD) yielded values of 1.5 to 23.0 microU/ml. All ophthalmic solutions tested failed to significantly lower serum glucose concentration or increase serum insulin concentration. Solutions used did not induce deleterious effect on ocular structures. Results indicate that topical administration of insulin-containing ophthalmic solution, either alone at the concentrations used or in combination with surface-acting agents, did not result in effective absorption of insulin across the conjunctival and lacrimal nasal mucosa in biologically relevant quantities. Thus, this route of insulin administration, under these specific conditions, is not an effective alternative or adjunct to SC administration of insulin for treatment of cats with insulin-dependent diabetes mellitus or severe noninsulin-dependent diabetes mellitus. PMID- 1883094 TI - Serially determined plasma alpha-tocopherol concentrations and results of the oral vitamin E absorption test in clinically normal horses and in horses with degenerative myeloencephalopathy. AB - Plasma alpha-tocopherol (vitamin E) values were monitored serially in 9 foals sired by a stallion with equine degenerative myeloencephalopathy (EDM) and in 5 age-matched control foals (sired by a clinically normal stallion) raised in the same environment for the first year of life. Clinical evaluation determined that 8 of the 9 foals sired by the stallion with EDM had neurologic deficits consistent with the disease on one or more occasions during the study period, whereas control foals had normal gait. From 6 weeks to 10 months of age, plasma alpha-tocopherol values in foals with signs of EDM were significantly (P less than 0.001) lower than those in control foals. An oral vitamin E absorption test was performed, and results for 8 of the affected horses and the affected stallion were compared with results for 4 of the monitored control horses and 4 additional control horses. Significant differences were not evident in any of the absorption indices. On the basis of data from this study and supported by reported prophylactic and therapeutic benefits of supplemented vitamin E, low plasma concentration of vitamin E is concluded to be a factor in the development of EDM in the first year of life of hereditarily predisposed foals. It was also concluded that the significantly lower alpha-tocopherol values seen in the foals in this study did not reflect a primary gastrointestinal tract absorption problem. PMID- 1883095 TI - Evaluation of the oral vitamin E absorption test in horses. AB - An oral vitamin E absorption test used in human beings was modified for use in horses. The most appropriate techniques with which to measure gastrointestinal tract absorption of vitamin E (alpha-tocopherol) in horses were developed. Vitamin E was administered orally, and serum values of alpha-tocopherol were measured by use of high-performance liquid chromatography at 0, 3, 6, 9, 12, and 24 hours after vitamin E administration. Variables included comparison of 2 dosages (45 and 90 IU/kg of body weight), routes of administration, and absorption dynamics of 3 preparations of dl-alpha-tocopherol. Absorption of the 2 doses of dl-alpha-tocopherol acetate indicated a dose response; the area under the curve at 24 hours (AUC24) was 4.3 micrograms.h/ml for the 45-IU/kg dose and 32.2 micrograms.h/ml (P less than 0.01) for the 90-IU/kg dose. Maximal absorption was apparent when vitamin E was naturally consumed in grain, compared with administration of identical preparations by stomach tube or paste. In the same horses, dl-alpha-tocopherol and dl-alpha-tocopherol acetate plus polyethylene glycol had statistically similar absorption curves and both had significantly greater AUC24, compared with dl-alpha-tocopherol acetate; values for the 3 compounds were 23.6, 25.8, and 12.6 micrograms.h/ml, respectively. The AUC24 varied between individual horses, but time of peak value was consistently observed between 6 and 9 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883096 TI - Erythrocyte insulin receptors in dogs with spontaneous hyperadrenocorticism. AB - Erythrocyte insulin receptor binding measurements were evaluated in 8 dogs with spontaneous hyperadrenocorticism. These dogs had normal serum glucose concentration, with normal to high serum insulin concentration (range, 45 to 1,400 pmol/L; normal, 40 to 170 pmol/L). Dogs with hyperadrenocorticism had significant (P less than 0.01) decrease in mean +/- SEM percentage of maximal binding for erythrocyte insulin receptors (2.25 +/- 0.21%), compared with results in 11 clinically normal pet dogs (4.29 +/- 0.42%). The decrease in erythrocyte receptor binding was attributed to significant (P less than 0.01) decrease in high-affinity receptor sites in dogs with hyperadrenocorticism (14.5 +/- 2.8), compared with clinically normal dogs (31.2 +/- 4.3). Significant differences in receptor affinity were not apparent between the 2 groups. Percentage of maximal binding for erythrocyte insulin receptors for dogs with hyperadrenocorticism was inversely correlated with serum insulin concentration (r = -0.85, P less than 0.01). Results indicate that the observed decrease in erythrocyte insulin receptor binding could contribute to insulin resistance and hyperinsulinemia associated with hyperadrenocorticism. Alternatively, decreased binding of insulin receptors in animals with hyperadrenocorticism may result from down-regulation secondary to hyperinsulinemia itself caused by insulin resistance at a postreceptor site (decreased responsiveness). PMID- 1883097 TI - Axial pattern flap based on the caudal auricular artery in dogs. AB - An axial pattern flap that was based on the sternocleidomastoideus branches of the caudal auricular artery and vein was developed. Control flaps, which included ligation and division of the caudal auricular artery and vein, were similarly developed on the contralateral aspect of the neck. Mean survival of caudal auricular artery axial pattern flaps (85.2%), compared with control flaps (63.9%), was significantly different (P less than 0.05). On the basis of results of this study, an axial pattern flap based on the sternocleidomastoideus branches of the caudal auricular artery and vein may be a source of skin for reconstructive procedures of the head and neck. PMID- 1883098 TI - Comparison of nonionic contrast agents iohexol and iotrolan for cisternal myelography in dogs. AB - During this investigation, the use of iohexol was compared with iotrolan for canine cisternal myelography. Iohexol and iotrolan myelography was done in 6 dogs by cisternal puncture with a 6-week interval between both procedures; each dog served as its own control. Cerebrospinal fluid (CSF) was collected for baseline analysis from each dog immediately before the contrast agent was injected. Cerebrospinal fluid samples were obtained at 1, 3, 7, and 14 days after injection of each contrast medium for cytologic and chemical analysis. Total CSF leucocyte count and glucose concentration did not change significantly in comparison with baseline data in any of the samples. After the injection of iohexol, protein concentration increased significantly in the 24-hour sample, and lactate dehydrogenase activity increased significantly in the 3-day sample. Significant difference was not found between the different samples collected at 1, 3, 7, and 14 days, compared with both contrast media. None of the dogs had seizure activity during a 5-hour postmyelographic observation period. Pathologic changes were not found by gross or microscopic examination of the spinal cord. Although a degradation in time of radiographic quality of all myelograms took place, the average radiographic score decreased more rapidly with iohexol. The average score at 90 minutes with iotrolan was comparable with the score at 45 minutes with iohexol, and the average score at 150 minutes with iotrolan was better than the score at 90 minutes with iohexol. At 5 and 10 minutes after cisternal injection, no significant difference was observable between the myelograms, but from 45 minutes onward, myelograms with iotrolan were superior. PMID- 1883099 TI - Effects of intra-articular administration of dimethylsulfoxide on chemically induced synovitis in immature horses. AB - The effects of intra-articular administration of dimethylsulfoxide (DMSO) on chemically induced synovitis in the middle carpal joint of 6 weanling horses were evaluated. Following aseptic collection of synovial fluid, the middle carpal joint of each forelimb was injected with 50 mg of Na-monoiodoacetate to induce synovitis. Eight days after injection, synovial fluid was obtained and the right middle carpal joints were injected with 2 ml of 40% DMSO in lactated Ringer solution. The corresponding joints of the left limb (control) were injected with 2 ml of lactated Ringer solution. Sampling and treatments were repeated on post injection days 11 and 14, for a total of 3 treatments. Horses were visually evaluated daily for lameness and joint effusion. Synovial fluid was evaluated for color and clarity, differential and total WBC count, total protein content, and hyaluronic acid concentration. The Kaegi gait analysis system provided an objective assessment of lameness prior to inducing synovitis, again on day 7, and on day 17. At necropsy (day 17), synovial fluid, synovial membrane, and articular cartilage specimens were collected. Joint effusion was evident 12 hours after injection of Na-monoiodoacetate in all joints. Mild lameness was evident at 24 hours; however, the lameness resolved by 72 hours. Objective assessment of lameness did not reveal significant differences between treatment or control limbs. Hyaluronic acid concentrations increased significantly (P = 0.023) above baseline values in most joints over the study period. Synovial fluid WBC counts increased significantly (P = 0.002) following Na-monoiodoacetate injection and remained significantly (P = 0.002) above baseline values throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883100 TI - Proto-oncogenes of genomic DNA in clinically normal animals of various species. AB - To provide information about oncogenes for molecular biological studies of tumors in domestic animals, the proto-oncogenes homologous to the c-myc, c-erbB-2, c-ros 1, c-yes-1, v-myc, v-Ki-ras, and v-Ha-ras oncogenes of genomic DNA in cattle, horses, pigs, dogs, cats, and chickens were investigated by Southern blot hybridization. High molecular weight genomic DNA in each of the animals contained proto-oncogenes that had a certain homology with the oncogenes used, but the extent of nucleotide homology of the proto-oncogenes differed in number and molecular weight: ie, 1 or 2 bands at 1.6 to 22.0 kilobase (kb) in the c-myc probe, 1 or 2 bands at 1.1 to 16.0 kb in the c-ros-1 probe, 1 to 3 bands at 0.7 to 23.0 kb in the c-erbB-2 probe, 1 to 4 bands at 0.6 to 18.0 kb in the c-yes-1 probe, 1 to 3 bands at 1.6 to 30.0 kb in the v-myc probe, 1 to 7 bands at 1.0 to 36.0 kb in the v-Ki-ras probe, and 1 to 4 bands at 1.0 to 27.0 kb in the v-Ha-ras probe. Furthermore, signal strength of each band, as determined by autoradiography, was not always the same for each probe in the various animals. Our findings indicate that these proto-oncogenes are well conserved with species specificities in each animal. PMID- 1883101 TI - Effect of milbemycin oxime against Ancylostoma caninum in dogs with naturally acquired infection. AB - Twenty-six mixed-breed (14 males, 12 females) dogs were used in a double-blind study to evaluate the effect of milbemycin oxime against naturally acquired infection with Ancylostoma caninum. Dogs were ranked and paired, on the basis of number of hookworm eggs/g of feces, and treatment was randomly assigned. Each dog was given either the study drug or placebo (1 tablet/11.4 kg [0.5 mg/kg] of body weight). Eggs per gram of feces enumeration was done on days 3 and 7 after treatment, and dogs were euthanatized on day 7. On day 3, 5 of the 13 dogs in the milbemycin-treated group had hookworm eggs in the feces (results of the McMaster test). In these dogs, mean number of eggs per gram of feces had decreased markedly (from 5,289 to 452) and, by day 7, was 114. At necropsy, 16 A caninum adults were recovered from 2 of the milbemycin-treated dogs. On day 3, 12 of the 13 dogs in the placebo-treated group had hookworm eggs in the feces. Mean number of eggs per gram of feces in these dogs decreased slightly (from 5,243 to 2,646), but did not decrease further by day 7. A mean number of 54.4 A caninum adults was recovered from 12 of the 13 placebo-treated dogs at necropsy. Milbemycin oxime had 97.8% efficacy against A caninum. Results also indicated that milbemycin oxime may be effective against Trichuris vulpis, but not against Dipylidium caninum. PMID- 1883102 TI - Comparison of four methods of estimating glomerular filtration rate in cats. AB - Four methods of evaluating renal function were performed in 6 cats anesthetized with halothane in oxygen. Glomerular filtration rate (GFR) was measured simultaneously in each cat by exogenous creatinine clearance (ECC), bolus inulin clearance, and 99mTc(Sn)-diethylene-triaminepentaacetic acid (DTPA) clearance determined by 2 different methods. In the first DTPA clearance method (DTPA-1), we measured radioactivity in serial blood specimens to construct plasma disappearance curves for calculation of GFR. In the second DTPA clearance method (DTPA-2), we used serial external head counts of radioactivity and a single blood specimen to construct plasma disappearance curves for calculation of GFR. Bolus inulin clearance was calculated from plasma disappearance curves using a 1 compartment open pharmacokinetic model (IN-1) and a 2-compartment open pharmacokinetic model (IN-2). Glomerular filtration rates were measured over 3 hours, for creatinine and DTPA methods, and over 4 hours for the inulin methods. The GFR obtained with the reference method (ECC) was 2.56 +/- 0.61 ml/min/kg of body weight (mean +/- SD). Values for GFR determined by ECC and DTPA-1 were significantly correlated (r = 0.852; P less than or equal to 0.05). Correlation between ECC and DTPA 2 was not as good (r = 0.783; P less than or equal to 0.10), but the 2 DTPA methods significantly correlated with one another (r = 0.897; P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883103 TI - Analysis of selected variables in the under-agarose assay for chemotactic responses of canine neutrophils. AB - Chemotaxis under agarose was evaluated to establish an assay system and to characterize chemotactic responses of canine neutrophils. A method for the measurement of canine neutrophil chemotaxis was established, with optimal responses obtained with agarose containing 10% pooled canine serum, a concentration of 5 x 10(5) cells/well, zymosan-activated serum (ZAS), or autologous serum or plasma as the chemoattractants, and a 120-minute incubation period. Canine neutrophils responded well to ZAS, heat-inactivated ZAS, autologous serum and plasma, and heat-inactivated pooled serum. Chemotactic activity was proportional to the concentration of serum used as the chemoattractant. Mean (+/- SD) random migration, chemotaxis, chemotactic index, and chemotactic differential of neutrophils from 9 healthy Greyhounds were 1.09 (+/- 0.23), 1.95 (+/- 0.38), 1.82 (+/- 0.31), and 0.86 (+/- 0.32) mm, respectively. PMID- 1883104 TI - Use of a multivariable indexing score for hygiene variables in relation to egg production. AB - An indexing system for hygiene variables associated with egg production was developed by use of data collected from chicken flocks in southern California. The data were analyzed by factor and regression analysis. On the basis of our findings, hygiene index in relation to egg production consists of ventilation system, cooling system, manure removal, and truck movement. Flocks kept under natural ventilation produced, on the average, 2% more hen-day eggs than flocks kept under artificial ventilation. Flocks placed in houses with roof sprinklers produced 3.3% more hen-day eggs, compared with flocks placed in houses with inside foggers and pad. Flocks kept under the system of frequent removal of manure produced 2% more hen-day eggs than flocks kept under the system for which the manure was removed less frequently. Flocks kept in farms that restricted trucks collecting dead birds from entering the premises produced 3.4% more hen day eggs than those that allowed such trucks to enter the farm. PMID- 1883105 TI - [Prevention of graft vs. host disease in pediatric post-transfusion patients]. PMID- 1883106 TI - [Evaluation of the serological follow-up of newborn infants, carriers of HIV-1 antibodies]. AB - Serological follow-ups were performed in 19 newborns carrying HIV 1 antibodies over a period ranging between 9 and 62 months. Eight children developed AIDS ans 11 remained asymptomatic. Anti-HIV 1 antibodies were determined by ELISA and Western blot and p 24 antigen was detected by ELISA. Antibodies to HIV 1 disappeared in most children without AIDS symptoms between 10 and 12 months after birth, with antibodies against gp 41 being lost first. Children with AIDS remained positive during follow-up, although in 3 cases with positive was absent in all the asymptomatic children, while it was present in 75% of the patients with AIDS. PMID- 1883107 TI - [Exposure to lead in infancy and childhood]. AB - We have made a study on lead poisoning taken from an ambulatory sample of 693 children belonging to Pediatric Department of Hospital General de Galicia (Santiago de Compostela), with ages between 1-14 years. Mainly, males (55.5%), rurals (79.5%) and from low-middle class (78.4%). A protocol, which includes clinic history, was applied to all the patients, together with social- demographic classification test, inquiries about possible sources of saturnism of their habitat and the different laboratory assays, blood and urine analysis and lead and erythrocyte zinc protoporphyrin (ZPP) concentrations in venous blood. In a second phase a test of lead mobilization with EDTA was done on the candidates as well as measurement of lead contents in their houses running water. Two groups were made according to, their ages, group A (1-6 years) 298 children (43%) and group B (7-14 years), 395 (56.9%) and their clinical signs, probably symptomatics 424 (61.1%) and controls 269 (38.8%). The frequency of lead overexposition is of eighteen patients (2.59%) and three are controls. All of then are rurals; high risk in eight of them (1.15%) and moderated in ten (1.44%). The concentrations in their houses running water exceed the 0.05 ppm limit. On our conclusions, we recommend the screening in children with some kind of risk and a list with other preventive measures. PMID- 1883108 TI - [Meningococcal sepsis in our area. Study of the disease severity factors and therapeutic management over a 10-year period]. AB - Meningococcal sepsis with cardiovascular manifestations is one of the leading causes of pediatric intensive care admission (14.85%) in our area. We carried out a two phase study over period of 10 years from 1979 to 1988, involving a retrospective analysis of clinical and analytical manifestations in order to determine a prognostic score of the severity of meningococcal infections in our area. A total of 86 cases were studies over a two year period. After establishing the prognostic score, we applied a previously assayed therapeutic protocol, based on the number of criteria of severity, in 170 children selected as having the same criteria. The factors of seriousness considered were: Appearance of the first symptoms less than 12 h. previously, appearance of petechia less than 6 h. previously, hyperthermia, shock at admission, absence of meningitis, fulminating course of purpura and convulsions, leukopenia less than or equal to 5,000 mm3, prothrombin activity less than or equal to 45%, platelets less than or equal to 75,000 mm3, fibrinogen less than or equal to 250 mgrs% and FPD greater than 40 micrograms/ml (p less than or equal to 0.01 (CHI SQUARE]. In the first phase of study, overall mortality was associated with the presence of three criteria, and was highest when more than seven criteria were present. The results indicate that mortality from meningococcal sepsis is linked to fulminating deterioration of hemodynamics and DIC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883109 TI - [Studying the levels of endotoxemia in meningococcal sepsis. Its relations to pregnancy and antibiotic treatment]. AB - The most frequent cause of toxic shock in our area is meningococcal sepsis. It is currently assumed that endotoxin produce by this bacteria, a lipopolysaccharide with toxic properties, is able to trigger shock and DIC by stimulating both arachidonic acid pathways, among other actions. Previous studies in our laboratory demonstrated significant differences (p +/- 0.001) in the amounts of endotoxins released in vitro by strains from patients and healthy carriers and statistically related criteria of severity with mortality in 256 patients in our center over the last 10 years. In the present study we attempted to establish whether plasma levels of endotoxin were correlated with the severity of the disease. We studied 32 patients with meningococcal sepsis, dividing the subjects into two groups: those in whom six or more criteria of severity were present, and those in whom less than six criteria were found. Blood levels of endotoxin were determined upon admission and after the administration of antibiotics (penicillin and chloramphenicol) using the limulus test with a chromogenic substrate (Coatest, Endotoxin, Kabivitrum, Sweden). Levels of endotoxins were significantly higher in patients with more than six criteria of severity both upon admission (0.6 +/- 0.03) ng/ml) and 4 h. afterward (0.74 +/- 0.006 ng/ml) in comparison to children in whom the clinical picture was less serious (0.27 +/- 0.18 ng/ml and 0.27 +/- 0.18 ng/ml and 0.27 +/- 0.16 ng/ml7 t = 5.8 y t = 5.6 respectively. Endotoxin levels were highest in patients presenting shock, disseminated intravascular coagulation in the hypocoagulability phase and more than 8 criteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883110 TI - [Ornithine transcarbamylase deficiency. Biochemical studies in the diagnosis of 4 cases and the identification of carriers]. AB - The biochemical studies for the diagnosis of four cases of OCT deficiency are described: two male sibs, with total enzymatic deficiency and neonatal death, and two symptomatic heterozygous females. The enzymatic activity was determined in hepatic necropsy or duodenal biopsy from these patients and carriers were identified among their relatives. The usefulness of the enzymatic analysis compared with the protein loading test followed by the determination of ammonia and orotic acid for the female carrier detection is discussed, and the interest of their identification to prevent the risk of hyperammonemic crisis with possible neurologic sequels is stressed. PMID- 1883111 TI - [Epidemiology of mental deficiency. The study of Safor (I): prevalence and etiology]. AB - An epidemiological study of Mental Deficiency was carried out in an area of the region of Valencia. A prevalence of children between 0-14 years old were found to have an IQ of below 70; 14,10 every 1,000 over a period from september 1987 to june 1988. This prevalence increases gradually according to age, reaching a high point at 10 and another at 14. These fluctuations are due to extreme and less serious cases. 29% of the cases can be attributed to prenatal causes. 9% are perinatal, and 49% are a postnatal origin. In 57% of the cases no cause has been found, and can be considered of unknown etiology. PMID- 1883112 TI - [Helicobacter pylori: a new pathogen to be considered in infancy]. AB - A prospective study in 11 consecutive children with gastroduodenal disease is presented. Endoscopic study and gastric biopsies were performed for histologic and bacteriologic research of H. pylori. Endoscopic studies in 7 of the patients showed lesions of antritis that were assessed by histopathologic study. H. pylori was isolated in 4 of them. The presence of H. pylori in the stomach of children with chronic gastritis is confirmed. It is remarked the importance of gastric biopsy, at least when the endoscopic study shows the presence of antral gastritis. PMID- 1883113 TI - [Traumatic rupture of the diaphragm in children: apropos of 2 cases]. AB - We present two patients with diaphragmatic rupture, right and left respectively, which occurred after thoracoabdominal traumatisms. Comments are made on the increase of this pathology in the pediatric population and the importance of an early diagnosis. We also revise the diagnostic procedures and underline the value of the chest roentgenogram to establish an early diagnosis. PMID- 1883114 TI - [Dietary guidelines for diet therapy of children with hypercholesterolemia]. PMID- 1883115 TI - [Intrapericardial teratoma. Report of a case]. PMID- 1883116 TI - [Ectopic spleen. Apropos of a case]. PMID- 1883117 TI - [Association of right diaphragmatic hernia and omphalocele: report of a case]. PMID- 1883118 TI - [Terminal deletion of the long arm of chromosome 4:46,XY, del (4) (q31.3----qter: a case after in vitro fertilization]. PMID- 1883119 TI - Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. AB - OBJECTIVES: To determine whether relative vitamin D deficiency during the winter months contributes to age-related bone loss and whether rates of change in hard- and soft-tissue mass vary during the year. DESIGN: Double-blind, placebo controlled, 1-year trial in 249 women in which equal numbers of women were randomized to either placebo or 400 IU of vitamin D daily. All women received 377 mg/d of supplemental calcium largely as calcium citrate malate. PATIENTS: Healthy, ambulatory postmenopausal women with usual intakes of vitamin D of 100 IU/d. MEASUREMENTS: Duplicate spine and whole-body scans were done by dual energy x-ray absorptiometry at 6-month intervals that were timed to periods when 25 hydroxyvitamin D levels were highest and lowest. Period 1 was June-July to December-January and period 2 was December-January to the next June-July. Serum parathyroid hormone and plasma 25-hydroxyvitamin D levels were measured during periods 1 and 2. MAIN RESULTS: In the placebo group, spinal bone mineral density increased in period 1, decreased in period 2, and sustained no net change. Women treated with vitamin D had a similar spinal increase in period 1 (1.46% compared with 1.40% in placebo), less loss in period 2 (-0.54% compared with -1.22%, CI for the difference, 0.05% to 1.31%, P = 0.032) and a significant overall benefit (0.85% compared with 0.15%, CI for the difference, 0.03% to 1.37%, P = 0.04). In period 2, 25-hydroxyvitamin D levels were lower and parathyroid hormone levels were higher in the placebo than in the vitamin D group. Whole-body lean and fat tissue and bone mineral density varied during the year but did not change overall. CONCLUSIONS: At latitude 42 degrees, healthy postmenopausal women with vitamin D intakes of 100 IU daily can significantly reduce late wintertime bone loss and improve net bone density of the spine over one year by increasing their intake of vitamin D to 500 IU daily. A long-term benefit of preventing vitamin D insufficiency in the winter seems likely although it remains to be shown. Observed changes in bone as well as in fat and lean tissue appear to be related to season. PMID- 1883121 TI - Sleep apnea in acromegaly. AB - OBJECTIVE: To provide information on the nature, prevalence, and severity of sleep apnea in patients with acromegaly. DESIGN: Consecutive case series. SETTING: Tertiary referral hospital. PATIENTS: Fifty-three patients with acromegaly were consecutively referred: 33 patients were referred because of clinical suspicion of sleep apnea and 20 patients were referred without suspected apnea. MEASUREMENTS: Sleep studies as well as growth hormone and insulin-like growth factor 1 (IGF-1) measurements were done. MAIN RESULTS: Thirty-one patients (93%; 95% Cl, 85% to 100%) referred because of suspicion of sleep apnea had sleep apnea compared with 12 patients (60%; Cl, 37% to 83%) referred without suspected sleep apnea. Patients with sleep apnea did not have biochemical evidence of increased disease activity (random growth hormone, 12.7 +/- 4.4 micrograms/L; mean growth hormone at 24-hour sampling, 10.8 +/- 8.4 micrograms/L; IGF-1, 90.0 +/- 7.5 nmol/L) compared with patients without sleep apnea (random growth hormone, 14.2 +/- 4.9 micrograms/L, P greater than 0.2; mean growth hormone, 12.4 +/- 3.5 micrograms/L, P greater than 0.2; IGF-1, 90.0 +/- 10.0 nmol/L, P greater than 0.2). Central sleep apnea was the predominant type of apnea in 33% (Cl, 18% to 47%) of patients and was associated with higher random growth hormone and IGF 1 levels than was obstructive apnea (random growth hormone, 23.4 +/- 3.9 compared with 8.8 +/- 3.1 micrograms/L, P less than 0.001; IGF-1, 126 +/- 17.5 compared with 72.5 +/- 7.5 nmol/L, P less than 0.01). CONCLUSIONS: Sleep apnea is common in acromegaly. The rate of central sleep apnea was unexpectedly high in patients with acromegaly, and biochemical evidence of increased disease activity was associated with the presence of central apnea rather than with the degree of sleep apnea. Altered respiratory control is a possible mechanism producing sleep apnea in acromegaly. PMID- 1883120 TI - Reversible renal insufficiency due to angiotensin converting enzyme inhibitors in hypertensive nephrosclerosis. AB - OBJECTIVE: To review the incidence of reversible renal insufficiency in patients with hypertensive nephrosclerosis undergoing antihypertensive therapy. DESIGN: Retrospective analysis of 73 patients in a long-term blood pressure control study that compared the effects of an angiotensin converting enzyme (ACE) inhibitor plus conventional antihypertensive agents compared with placebo plus antihypertensive agents. SETTING: Hospital-based outpatient treatment center. INTERVENTIONS: Patients were divided into group 1, which received enalapril plus conventional antihypertensives, and group 2, which received placebo plus conventional antihypertensives. MEASUREMENTS: Blood pressure and serum creatinine levels were measured, and imaging studies of the main renal arteries were done. MAIN RESULTS: In group 1, eight of 42 patients (19%, 95% CI, 9% to 34%) developed reversible renal insufficiency, defined as an unexpected increase in serum creatinine of 88 mumol/L or higher. Six episodes of reversible renal insufficiency occurred during July and August when temperatures were 32.2 degrees C to 37.8 degrees C (90 degrees F to 100 degrees F). Renal artery stenosis was excluded by renal arteriogram or ultrasonic duplex scanning. All eight group-1 patients had a significant decrease in mean arterial pressure below their baseline level during reversible renal insufficiency (mean change, -28 +/- 10 mm Hg, P less than 0.001). The increase in the serum creatinine level was inversely correlated with the decrease in the mean arterial pressure (r = -0.68, P less than 0.01). Reversible renal insufficiency was successfully managed by withdrawing or reducing enalapril as well as other antihypertensive agents. Subsequently, enalapril was tolerated by seven of the eight patients without recurrence of renal insufficiency. In contrast, none of 31 (CI, 0% to 11%) patients in group 2 developed reversible renal insufficiency despite the fact that both the incidence of decreases in mean arterial pressure in 6 of 31 patients (19%) and the magnitude of the decreases in mean arterial pressure (mean change, -33 +/- 16 mm Hg) were similar to those observed in group 1. CONCLUSIONS: Reversible renal insufficiency in hypertensive nephrosclerosis associated with ACE inhibitor therapy correlates with relative hypotension, is not dependent on renal artery stenosis, and can usually be managed by dose reduction. PMID- 1883122 TI - The T-cell proliferative assay in the diagnosis of Lyme disease. AB - OBJECTIVE: To determine the sensitivity and specificity of the T-cell proliferative assay as a diagnostic test in Lyme disease. DESIGN: Cross-sectional study of patients with Lyme arthritis or chronic neuroborreliosis who had a history of erythema migrans, positive antibody responses to Borrelia burgdorferi by enzyme-linked immunosorbent assay (ELISA), or both; patients with other diseases; and healthy subjects. SETTING: Diagnostic Lyme disease clinic in a university hospital. PATIENTS: Forty-two of the 67 patients with active Lyme arthritis or chronic neuroborreliosis who were seen during the study period; 16 patients with inactive late Lyme disease; 77 patients with other rheumatologic or neurologic diseases; 9 workers from the Borrelia laboratory; and 9 healthy subjects. MEASUREMENTS AND MAIN RESULTS: Nineteen of 42 patients with Lyme arthritis or chronic neuroborreliosis and 4 of 77 patients with other diseases had positive T-cell proliferative responses to B. burgdorferi antigens. The sensitivity of the proliferative assay was 45% (95% Cl, 30% to 60%) and the specificity was 95% (95% Cl, 87% to 99%). Twelve of 27 patients with active Lyme arthritis, 7 of 15 patients with chronic neuroborreliosis, 4 of 16 patients with inactive Lyme disease, 4 of 9 healthy Borrelia laboratory workers, and 0 of 9 healthy subjects had positive responses. Three of five patients with Lyme disease who had negative or indeterminant antibody responses by ELISA had positive T-cell proliferative responses. CONCLUSION: The T-cell proliferative assay may be a helpful diagnostic test in the small subset of patients with late Lyme disease who have negative or indeterminant antibody responses by ELISA. PMID- 1883123 TI - Influence of gastric acidity on the bioavailability of digoxin. AB - OBJECTIVE: To study how changes in gastric acidity induced by omeprazole and pentagastrin affect the absorption of unchanged digoxin and its hydrolytic breakdown products. DESIGN: Double-blind, double-dummy, randomized, crossover study. SETTING: Academic department of clinical pharmacology. SUBJECTS: Six healthy male volunteers. INTERVENTIONS: Subjects received digoxin, 1 mg orally, on three separate occasions: first, after pretreatment with omeprazole; second, after pretreatment with pentagastrin; and third, after "pretreatment" with placebo. MEASUREMENTS: The in-vitro decomposition of digoxin wa studied using a standard dissolution test. The urinary excretion of digoxin over a 120-hour period was measured using selective high-pressure liquid chromatography (HPLC) and a polarization enzyme immunoassay (EIA). Plasma concentrations were measured at 2 hours with the EIA. MAIN RESULTS: Digoxin was rapidly released from the tablets in the in-vitro test. At acid pH, decomposition (as measured with HPLC) was rapid. Pentagastrin reduced the urinary excretion of unchanged digoxin, as measured by HPLC, from 34% to 21.4% of the dose (difference, -12.6%; 95% Cl, 23.5 to -1.8; P less than 0.05), whereas omeprazole increased urinary excretion to 47.4% (difference, 13.4%; 95 Cl, 2.5% to 24.4%; P less than 0.05). However, such differences were not found with the nonselective polarization EIA. CONCLUSIONS: Our data suggest that gastric acidity causes the breakdown of digoxin to products that cross-react in the assay (EIA) that is commonly used clinically. In patients with reduced gastric acidity, increased plasma concentrations of unchanged digoxin may not be detected because of limitations of the EIA, which may invalidate the quantitative use of the plasma digoxin concentration as a predictor of digoxin toxicity. Omeprazole, and presumably other gastric-acid inhibitors, may increase the bioavailability of unchanged digoxin. PMID- 1883124 TI - Allergic bronchopulmonary aspergillosis with adenopathy. PMID- 1883125 TI - NIH conference. Systemic lupus erythematosus. AB - Although the cause of systemic lupus erythematosus remains unknown, pathogenic mechanisms are becoming clearer. Both genetic and environmental factors have been implicated in the induction and in the perpetuation of lupus. Implicated environmental triggers include ultraviolet light, chemicals (hydrazines, hair dyes, drugs), some foods, and possibly infectious agents. Lupus is mediated by the immune system. Patients have excess numbers of antibody-forming cells, including those that produce antibodies reactive with self-antigens. Patients also have an increased number of activated T cells, some of which help B cells to produce autoantibodies. A loss of tolerance is a critical immune abnormality in lupus; many of the activated helper T cells may result from a failure in normal tolerance mechanisms. A hematopoietic stem-cell defect could give rise to both B- and T-cell abnormalities. Such a stem-cell abnormality might lead to both a loss of self-tolerance and polyclonal B-cell activation. Antigen-driven, T-cell dependent expansion of B-cell clones would then give rise to pathogenic autoantibodies, including anti-DNA. We believe that lupus is a syndrome: Patients differ regarding specific inciting factors and immune defects. Some patients have genetically conditioned abnormalities, similar to those found in mice with lupus; others have a combination of genetic and acquired defects. We hope that insights into pathogenesis lead to improved and more individualized therapy. PMID- 1883126 TI - When should patients with lethal ventricular arrhythmia resume driving? An analysis of state regulations and physician practices. AB - Most states have specific laws governing whether patients with seizure disorders can drive. To learn whether similar laws exist for patients with lethal ventricular arrhythmias, we surveyed the Departments of Motor Vehicles in all 50 states. In addition, either an arrhythmia specialist (n = 25) or a general cardiologist (n = 25) was chosen randomly from each state and interviewed to study physician awareness of such laws and physician attitudes toward driving by patients with arrhythmias. Forty-two states (84%) have laws restricting driving by patients who have seizures; only 8 states (16%) have specific laws for patients with arrhythmias. No state makes a distinction between driving by patients with arrhythmias who are managed with an implantable cardioverter defibrillator (ICD) compared with patients who are managed medically. Seventy four percent of physicians did not know their own state's laws about driving by patients who have ventricular arrhythmias. Cardiologists were more likely to advise no driving restriction for medically treated patients than for ICD-treated patients. Cardiologists were also more likely to advise permanent restriction for patients with ICDs than for patients treated medically. We conclude that greater legal and medical consensus is needed to guide physicians in advising patients with lethal ventricular arrhythmias about driving restrictions. PMID- 1883127 TI - Three women at Johns Hopkins: private perspectives on medical coeducation in the 1890s. PMID- 1883128 TI - Anemia of chronic disease: a misnomer. PMID- 1883129 TI - Disseminated candidiasis after intravenous use of oral methadone. PMID- 1883130 TI - Standardizing fecal occult blood testing. PMID- 1883131 TI - Octreotide for diarrhea in amyloidosis. PMID- 1883133 TI - Cardiopulmonary resuscitation in teaching hospitals. PMID- 1883132 TI - Diagnosing Lyme disease. PMID- 1883134 TI - A library for internists. PMID- 1883135 TI - Defensive medicine: a form of "varmint" control? PMID- 1883136 TI - Silent synaptic connections and their modifiability. AB - Comparison of the two afferent systems illustrates certain features common to synaptic transmission as well as differences that might be important for synaptic plasticity. Transmission at both the inhibitory and excitatory connections is satisfactorily described by a simple binomial model that considers the average probability of release to be the same at each active site, although it should be stressed that the best evidence derives from the first set of afferents. Another similarity between the two systems is that short-term changes in synaptic efficacy, namely, facilitation and depression, appear to be due to changes in p. We previously suggested that both phenomena occur during repetitive stimulation, with the dominant effect depending upon the initial probability of release. It remains to be seen if depression dominates at other inhibitory connections, although it is already clear that one cannot generalize about excitation, because some excitatory junctions have an initial high p and exhibit a marked depression rather than the facilitation described here. We have found no evidence for the notion that some synapses within a connection may be silent. That idea has been proposed, but not proven, for other synaptic connections in the vertebrate central nervous system. Indeed, it will be difficult to assess as long as quantal release cannot be reliably detected at these junctions, and morphological confirmation at the ultrastructural level will also be required. On the other hand, evidence from a few peripheral junctions where one presynaptic afferent establishes hundreds of contacts with its target cell, does suggest the possibility of silent synapses, or at least an extremely low probability of release in those cases. These situations may correspond to extremes of our finding that as the number of release sites increases, p decreases. Regardless, the inverse relation between n and p suggests caution should be exercised in interpreting data indicating that synaptic plasticity is associated with increased numbers of synapses between two cells. Although we have not detected silent synapses within a transmitting connection, we have observed chemically silent connections between neurons, and the evidence reviewed here suggests transmission may be blocked postsynaptically, as with the inhibitory connections, or presynaptically, as with the excitatory ones. Although the underlying mechanisms are only partially elucidated, it is also clear that such connections can be switched into a transmitting mode. Consequently, they may provide a significant reserve that might well become functional in different behavioral states or in response to certain patterns of activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1883137 TI - Morphological aspects of synaptic plasticity in Aplysia. An anatomical substrate for long-term memory. AB - The morphological basis of long-term sensitization of the gill-and-siphon withdrawal reflex in Aplysia was explored by examining the structure of identified sensory neuron synapses in control and behaviorally modified animals. Following long-term training, sensitized animals displayed an increase in the number of sensory neuron synapses compared to control animals. The relative permanence of these structural changes and their similarity in time course to the behavioral duration of sensitization suggest a role for synapse number changes during long-term memory. PMID- 1883138 TI - Cerebellar synaptic plasticity. Relation to learning versus neural activity. PMID- 1883139 TI - Multiple modes of neuronal population activity emerge after modifying specific synapses in a model of the CA3 region of the hippocampus. PMID- 1883140 TI - Cerebellum and classical conditioning of motor responses. PMID- 1883141 TI - Substrates for motor learning. Does the cerebellum do it all? PMID- 1883143 TI - Operantly conditioned plasticity in spinal cord. AB - Recent work has shown that the monosynaptic pathway of the SSR can be operantly conditioned, and that a significant part of the plasticity responsible for the behavioral change resides in the spinal cord. The most likely sites of this activity-driven plasticity are the synapse of the Ia afferent neuron on the motoneuron and/or the motoneuron itself. Because the SSR pathway is the simplest and most accessible stimulus-response pathway in the vertebrate CNS, it may provide a valuable experimental model for elucidating activity-driven CNS changes responsible for learning. PMID- 1883142 TI - A model of adaptive control of vestibuloocular reflex based on properties of cross-axis adaptation. PMID- 1883144 TI - Spontaneous bioelectric activity as both dependent and independent variable in cortical maturation. Chronic tetrodotoxin versus picrotoxin effects on spike train patterns in developing rat neocortex neurons during long-term culture. PMID- 1883145 TI - Developmental visual plasticity in Drosophila. PMID- 1883146 TI - Relationship between tubulin delivery and synapse formation during goldfish optic nerve regeneration. PMID- 1883148 TI - Influence of temperature on adaptive changes of the vestibuloocular reflex in the goldfish. PMID- 1883147 TI - Dual effects of the protein kinase inhibitor H-7 on CA1 responses in the hippocampal slice. PMID- 1883149 TI - Effect of MK801 on long-term potentiation in the hippocampal dentate gyrus of the unanesthetized rabbit. PMID- 1883151 TI - Chronotherapy of malaria: identification of drug-sensitive stage of parasite and timing of drug delivery for improved therapy. AB - The cyclic nature of malarial fever in conjunction with the pharmacokinetic characteristics of antimalarial drugs, call for the conception of a chrono therapeutic approach for the treatment of the disease. An experimental murine malarial model was devised using the highly synchronous species Plasmodium vinckei petteri to test this rationale. Sub-curative doses of chloroquine were injected sub-cutaneously to mice either during the prepatent period or during patent infection. Inspection of the effect of drug applied at different stages of the parasitic cycle, revealed that medium size trophozoites (MT) were the most susceptible stage to chloroquine, while ring and young trophozoite stages were refractory to the drug. Chloroquine given during these latter stages, affected the parasites when they developed into the MT stage. Drug treatment during the MT stage phase-shifted the schizogonic cycle by 18 hours. Hence, treatment with two consecutive injections given 18 hours apart, i.e. timed to the overwhelming presence of the MT stage in the circulation, gave the best therapeutic results. PMID- 1883152 TI - Hyperendemic onchocerciasis in the Taraba river valley of Gongola state (Old Adamawa province), Nigeria. AB - A survey of the prevalence of onchocerciasis was carried out in the Taraba river valley, Nigeria where Simulium damnosum s. l. is known to breed but about which no epidemiological data exists. Skin biopsies taken from 2,876 persons in 14 communities were examined for the microfilariae of Onchocerca volvulus. 100% infection rate was recorded in one of the communities, five other communities had prevalence rates between 81.0% and 94.7%. Three communities had infection rates between 44.8% and 69.1%. The mean microfilarial density in all the communities was 64.7 with a range between 3.2 and 167.6. The present findings indicate that the Taraba river valley may be one of the worst onchocerciasis zones in Nigeria. PMID- 1883150 TI - Three-dimensional imaging of neurophysiologically characterized hippocampal neurons by confocal scanning laser microscopy. PMID- 1883153 TI - The application of the statistical study in the morphometric characterization of a Colombian strain of Trypanosoma cruzi. AB - After morphological and histopathological characterization, the Cali strain of T. cruzi isolated from a patient in Cali (Colombia), was also submitted to a morphometrical characterization. For this we estimated 16 cellular parameters in 30 samples of each evolutive form of T. cruzi in blood in NNN medium through planimetry by the IBAS-1 (Image Basic Analytic System). This morphometrical study was completed with a statistical one through the application of the variance (ANOVA-1). This made it possible to evidence a great number of significant differences between the slender, broad and stout forms and also between the short and large epimastigotes from the NNN medium. These data have a real interest for classifying some features of the biological cycle of T. cruzi as well as the future development of diagnosis techniques or therapeutical and prophylactic experiments. PMID- 1883154 TI - The effects of early postoperative radiation on vascularized bone grafts. AB - The effects of early postoperative radiation were assessed in free nonvascularized and free vascularized rib grafts in the canine model. The mandibles of one-half of the dogs were exposed to a cobalt 60 radiation dose of 4080 cGy over a 4-week period, starting 2 weeks postoperatively. The patency of vascularized grafts was confirmed with bone scintigraphy. Histological studies, including ultraviolet microscopy with trifluorochrome labeling, and histomorphometric analyses were performed. Osteocytes persist within the cortex of the vascularized nonradiated grafts to a much greater extent than in nonvascularized, nonradiated grafts. Cortical osteocytes do not persist in either vascularized or nonvascularized grafts subjected to radiation. New bone formation is significantly retarded in radiated grafts compared with nonradiated grafts. Periosteum and endosteum remained viable in the radiated vascularized grafts, producing both bone union and increased bone turnover, neither of which were evident to any significant extent in nonvascularized grafts. Bone union was achieved in vascularized and non-vascularized nonradiated bone. In the radiated group of dogs, union was only seen in the vascularized bone grafts. PMID- 1883155 TI - Pediatric mandibular fractures. AB - In spite of curiosity, facial fractures, particularly mandibular fractures, in the pediatric age group embrace only a modest proportion of facial fractures that occur within the general population. Several large series report an overall incidence of approximately 1% of all facial bone fractures. A considerable volume of literature has been generated describing the pattern of injury and treatment modalities for pediatric facial bone fractures. At our institution, which is an extremely busy university-based regional trauma center, we have witnessed a persistent escalation in the number of patients requiring repair of their facial bone fractures. During the period of January 1989 through January 1990, we treated a total of 204 patients for repair of mandible fractures. An analysis of the records of this group revealed only 3 patients who were younger than 4 years of age and 2 additional patients younger than 8 years. There were another 10 patients 17 years and younger, for a total incidence of 0.08%. Additionally, we found that within this seemingly small group, there was a surprisingly high incidence of severe, associated injuries. PMID- 1883156 TI - Isle of palm and sole fillet flaps. AB - Extensive extremity injuries appropriately managed by immediate amputation may be compromised if retained soft tissues are inadequate to permit a simple wound closure. In usual circumstances, if the foot or hand from the soon-to-be discarded part has not been violated and, by chance, remains viable through a major neurovascular pedicle, then a fillet of the sole or palm fashioned as a local island flap may be used for durable and potentially sensate stump coverage. Function preservation by salvaging maximal amputation stump length could then be achieved in lieu of more complex microsurgical techniques. PMID- 1883158 TI - External septorhinoplasty in the cleft lip nose. AB - When the entire septum as well as the cartilaginous vault are exposed to direct vision by degloving the nasal covering, the complete extent of the deformities in cleft lip nose can be clarified. The septal cartilage is hollowed out leaving an L-shaped anterosuperior portion, whereas the intranasal structures are simultaneously altered to ensure the patency of the nasal airway. An adequate sized piece is cut from the removed cartilage and is fitted to the anterior part of the remaining cartilage to enforce the columella, which acts as a strut to keep both lower lateral cartilages symmetrical and to create a nasal tip. Thus, a new cartilaginous pyramid with symmetrical nostrils is reconstructed. If the anterosuperior portion of the cartilage is deviated, the concave surface is scored to allow it to be straightened before the strut is fitted. Satisfactory cosmetic and functional results were obtained in most patients with adult cleft lip nose, including those associated with deviation, without any major complications. PMID- 1883157 TI - Gore-Tex for augmentation of the nasal dorsum: a preliminary report. AB - Many different materials have been used to provide augmentation of the nasal dorsum. This includes both autogenous and homogenous materials, as well as allografts. Many times autogenous material is not readily available and homogenous materials have recently demonstrated significant absorption. Several artificial materials have been used in the past, including Supramid, silicone, and Proplast, each with its own limitations or problems. Two years ago we began using Gore-Tex Soft Tissue Patch as a material to augment the nasal dorsum. Although our experience is preliminary, certainly, experience with this material in cardiac and abdominal surgery is extensive. Our initial impression is that this material is a very useful alternative to traditional methods of nasal augmentation. PMID- 1883159 TI - Class II antigenicity of human cartilage: relevance to the use of homologous cartilage graft for reconstructive surgery. AB - The presence and distribution of class II transplantation antigens was studied on fresh and Merthiolate-preserved human nasal, tracheal, auricular, and rib cartilage using monoclonal antibodies in an indirect immunoperoxidase method. Substantial class II antigen expression was found on cells of the superficial area of the perichondrium of the nasal, auricle, and tracheal cartilages. In contrast, cartilage tissue lacked cells with detectable class II antigens. Our results indicate that the host response to fresh cartilage graft is induced by class II antigens presented in the perichondrium. A complete disappearance of this class II antigenicity of perichondrium can be achieved by means of an adequate Merthiolate preservation. PMID- 1883160 TI - The use of 5-aminoimidazole-4-carboxamide riboside (AICA riboside) to improve random skin flap viability in the rat model. AB - Several experimental studies have demonstrated that granulocytes have an important role in causing the necrosis of ischemic tissue by capillary plugging and superoxide radical formation. Adenosine is spontaneously released by ischemic cells and inhibits the granulocytic superoxide radical formation. 5 Aminoimidazole-4-carboxamide riboside, a naturally occurring by-product in purine biosynthesis, stimulates the release of ischemic cell adenosine and indirectly blocks the granulocyte-induced tissue necrosis. 5-Aminoimidazole-4-carboxamide riboside (10-500 mg/kg) was administered intraperitoneally in a blinded fashion once (single dose, 30 minutes before surgery) or twice (double dose, 30 minutes before and 5.5 hours after surgery) in groups of rats. The controls received intraperitoneal saline solution in the same fashion. Each rat underwent the elevation of a caudally based random skin flap. The flap viability was determined in a blinded fashion on the seventh post-operative day and statistically compared by Fisher's exact test. When 300 or 500 mg/kg of 5-aminoimidazole-4-carboxamide riboside was given as a single dose, the mean percentage of rat skin flap necrosis (19.4% +/- 3.1% and 19.6% +/- 4.2%, respectively) was lower but not significantly different from that of the control group of rats (29.3% +/- 2.7%) (p less than 0.08). Additionally, two doses of 500 mg/kg of 5-aminoimidazole-4 carboxamide riboside yielded a mean percentage of rat skin flap necrosis (12.24% +/- 4.58%) much lower (21.68% +/- 3.18%) than that of the control group of rats (p = 0.056). Our blinded fashion study demonstrated an almost statistically significant reduction of random skin flap distal necrosis after intraperitoneal injection of high doses of 5-aminoimidazole-4-carboxamide riboside.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883161 TI - The safety of intravenous fluorescein administration. AB - Intravenous fluorescein is frequently used to assess tissue perfusion and predict flap viability, although its safety has recently been questioned due to cardiovascular side effects. Vital signs of 50 patients who received fluorescein were monitored by anesthesiologist to assess flap viability. Blood pressure readings were recorded at 5-minute intervals for at least 1 hour before and after fluorescein administration. Repeated measure analysis of variance was performed to determine any significant sustained (greater than or equal to 30 minutes) or transient (less than or equal to 15 minutes) differences in pressure changes after fluorescein administration. No significant (p less than or equal to 0.1) differences in pressure were noted for any identifiable group of patients. Minor reactions included transient nausea with no vomiting (5), sustained blood pressure increases of greater than 10% preadministration values (9), transient pressure drops of greater than 10% (10), and sustained pressure drops of greater than 10% (4). These 4 patients responded to increased fluid therapy without need for pressor agents. PMID- 1883162 TI - The importance of near total resection of the corpus spongiosum and total resection of the corpora cavernosa in the surgery of male to female transsexuals. AB - From 1980 to 1989, 13 male to female transsexuals underwent surgery for resection of the corpus spongiosum, performed at the Department of Plastic and Reconstructive Surgery of the Free University Academic Hospital, Amsterdam, The Netherlands. Except for 1, all patients underwent the primary sex-reassignment procedures in institutions other than this hospital. All had difficulties during sexual activities. After repeat surgery with near complete excision of the corpus spongiosum and also in three instances of the corpus cavernosum, improvement was noticed in all patients. The importance of the total elimination of the erectile tissue is emphasized. PMID- 1883163 TI - Hypothetical chordee: skin shortage. PMID- 1883164 TI - Methylmethacrylate implants: a scanning electron microscopic study. AB - Two methylmethacrylate orbital implants used for 34 and 5 years, respectively, were examined with a scanning electron microscope. One of the implants was a combination of a prosthesis and an implant containing a magnet. The magnetic force had decreased markedly, and rust crystals were apparent. The methylmethacrylate surface was irregular and rough. PMID- 1883165 TI - The chemical peel. AB - Chemical peeling of facial skin has become a valuable adjunct in the armamentarium of the facial aesthetic surgeon. Among the various techniques available, phenol solutions are the most commonly used. Peeling produces a controlled, partial-thickness chemical burn of the epidermis and the outer dermis. Several techniques are available to "fine tune" the depth of the peel. Regeneration of peeled skin results in a fresh, orderly, organized epidermis. In the dermis, a new 2- to 3-mm band of dense, compact, orderly collagen is formed between the epidermis and the underlying damaged dermis, which results in effective ablation of the fine wrinkles in the skin and a reduction of pigmentation. These clinical and histological changes are long lasting (15-20 years) and may be permanent in some patients. Because of the metabolism and systemic complications of phenol, patient selection should involve systemic evaluation of liver, renal, and cardiac function, as well as an evaluation of the skin quality and medication status of the patient. Because of potential cardiac arrhythmias, peeling must be performed in a medically supervised environment, with continuous cardiac monitoring. The local complications of peeling include pigmentation changes, scarring, milia, ectropion, infection, activation of herpes simplex, and toxic shock syndrome. PMID- 1883166 TI - The rectus femoris myocutaneous flap for closure of difficult wounds of the abdomen, groin, and trochanteric areas. AB - The rectus femoris myocutaneous flap has proved to be an effective means of closing particularly difficult wounds in 2 patients. One patients had a massive defect in the lower abdomen, pubic, and right groin area after the radical resection of a recurrent pleomorphic liposarcoma of the spermatic cord. The second patient presented with a huge, right greater trochanteric wound measuring 15 cm in diameter. Both patients progressed to relatively uneventful primary healing. PMID- 1883167 TI - Penile replantation. AB - Amputation of the penis is thankfully an uncommon injury. Because of its rarity, a uniform plan of management to deal with this difficult injury has yet to be agreed on. We describe a man who sustained such an injury and his subsequent clinical course. The relevant history and pertinent anatomy is highlighted. Additionally, a systematic approach to dealing with this devastating injury is presented. PMID- 1883168 TI - High-voltage electrical injury: electron microscopic findings of injured vessel, nerve, and muscle. AB - Bilateral legs damaged by high-voltage electrical injury were treated by amputation and a free thin rectus abdominis myocutaneous flap with reduced muscle. Damaged arteries at 2 months after injury showed disappearance of endothelium, and a decreased number and morphological changes in smooth-muscle cells. Injured nerves and muscles showed early regenerating processes after total degeneration, and no progressive muscular necrosis. These results suggest that severe degeneration of the neurovascular bundle and muscle is unavoidable in high voltage electrical injuries of the extremities. Therefore, early amputation, sequential debridement, late coverage by a flap, and prolonged rehabilitation are required in this injury. PMID- 1883169 TI - Mercury poisoning from intravenous injection: treatment by granuloma resection. AB - Intravenous injection of mercury is a rare event. Mercury administered by this route may have several different consequences. In addition to elevated serum mercury levels, the diagnosis may be made by radiographic detection of metallic densities in the chest and at the sites of injection. Death due to mercury intoxication is unusual. Impairment of renal and hepatic function may occur. Our patient presented with gingivitis and a dentoalveolar abscess. Dense granulomas occur at the sites of injection. Treatment for these patients should include granuloma excision as the benefit of chelating agents, for chronic mercury intoxication is questionable. Skin and granuloma resection may leave vital structures exposed, necessitating flap coverage. PMID- 1883170 TI - Hook forceps. AB - A new pair of forceps incorporating two skin hooks and needle driver tips on an Adson forceps frame is described. Its use, advantages, and disadvantages are outlined. PMID- 1883171 TI - Rhinoplasty saw: a modified design. AB - One of the instruments used for osteotomies of the nasal bones in rhinoplasty is the saw. During the initial sawing movements, it is not uncommon to make multiple cuts in the bone. To avoid this problem, we have designed a modification of the Joseph's saw. The new design essentially fixes the saw along a single axis, producing a single and precise bone cut. This saw is useful for basal and superior osteotomies in rhinoplasties and is especially indicated in secondary rhinoplasties. PMID- 1883172 TI - An easy-to-make, easy-to-use device for preoperative marking for reduction mammoplasty and mastopexy. AB - A simple, convenient, and inexpensive device for preoperative marking in breast surgery is described. Its design is based on accepted surgical techniques and geometrical principles and obviates the use of multiple instruments commonly used. Its use allows accurate and expeditious planning, measuring, and marking. PMID- 1883173 TI - Stitch removal from hair-bearing areas: a simple method. AB - A simple method to ease the removal of stitches in hair-bearing areas is presented. The method consists of applying a depilatory cream to remove the masking hair. PMID- 1883174 TI - Congenital malformations in Toa Payoh hospital--a 18 year experience (1972-1989). AB - A ten year experience (1972-1981) of congenital malformations in Toa Payoh Hospital was presented previously. The experience of birth defects of the second decade (1982-1989) is reviewed and compared. The mortality rates of babies with malformations ranged from 1.52 to 3.55 per 1000 livebirths. There was no significant increase in congenital malformation death rates over the past eight years. There was an increasing trend of malformation deaths among the total neonatal deaths from 1972-1981 (p less than 0.05), but this was not so for the period 1982-1989. The incidence of minor congenital malformations has not changed except that more cases of undescended testes were recorded (p less than 0.05). Central Nervous System (CNS) malformations, congenital heart defects and chromosomal abnormalities still remain the leading cause of malformation deaths. Neural Tube Defects (NTD) were the commonest type of CNS defect and the death rates of NTD for these two periods remain the same (about 0.65 per 1000 births). The prevalence of anencephaly at birth in Chinese and Malay from 1982-1989 is 0.45 and 0.84 per 1000 livebirths respectively. Down syndrome was the commonest type of chromosomal abnormality (63%) and coarctation of aorta (40%) was the commonest type of congenital heart disease causing death. Many congenital malformations are genetically determined. More knowledge of the aetiological factors, antenatal diagnosis of birth defects, preventive measures and genetic counselling are, therefore, important in lowering birth defect rates. PMID- 1883175 TI - Epidemiology of injuries in Singapore. AB - Injuries are a major public health problem in developed industrialised countries and are the leading cause of premature mortality. This study has shown the same picture for Singapore. Injuries are the fifth leading cause of crude death but the most important cause of premature mortality being responsible for 23,800 potential years of life lost before the age of 65 years. The most vulnerable ages are from the preschool to the economically active age groups. Singapore males have twice the death rate of females (52 vs 20 per 100,000 population) because of the relatively higher proportion of males (78.5% among males vs 48% among females) who work and are therefore at higher risk. Indian males have the highest ethnic-and-sex-specific mortality rates (107 vs 48 among Chinese males and 39 among Malay males per 1000 population). Road traffic accidents were the leading cause of mortality from injuries but this has been over taken by suicides. Information on the specific causes and specific high risk behaviour and factors for injuries in Singapore is weak. This needs to be strengthened to enable more effective cause-specific control programmes to be drawn up. PMID- 1883176 TI - Evaluation of obstructive sleep apnoea in Singapore using computerised polygraphic monitoring. AB - There is no information of the prevalence and severity of obstructive sleep apnoea (OSA) in Asian snorers. One reason is the complexity and cost of a full polysomnographic recording. We have studied 37 snorers using an ambulatory recording system (Vitalog CA). Overnight recordings for seven hours were made of: 1) Respiratory pattern using respiratory inductance plethysmography; 2) Heart rate from the electrocardiograph (ECG); 3) Body position; 4) Body movements; 5) Oxygen saturation using finger-probe oximetry. The data were stored and analysed and scored using a dedicated microcomputer. Twenty-eight patients had OSA based on polygraphic criteria. The most consistent clinical findings in these patients were daytime somnolence and short thick necks. Respiratory events, oximetry and arousals during sleep showed a graded response according to the severity of excessive daytime somnolence. We conclude that OSA may not be uncommon in Asian patients and that the clinical severity can be confirmed by simplified polygraphic recordings using microcomputer analysis. PMID- 1883177 TI - Suicide and schizophrenia in Singapore--a fifteen year follow-up study. AB - This is a prospective follow-up study of 482 schizophrenic patients. At the end of 15 years, 41 had died of suicide and 30 had died of natural causes, giving a suicide rate of 567 per 100,000 per year. Suicide patients were significantly younger and experienced less delusion at the time of their first presentation. There were otherwise no significant differences in the socio-demographic or clinical variables between the suicide group and the controls (surviving patients). Jumping from height was the commonest method of suicide and our rate of suicide for schizophrenia is comparable to those reported in the literature. PMID- 1883178 TI - New admissions to a psychiatric ward in a general hospital. AB - A study of 343 new patients in the first psychiatric department in a general hospital in Singapore revealed a large proportion (40%, n = 137) of neurotic patients, especially neurotic depressives (n = 76). The next largest group is the non-organic psychoses 35% (n = 120), most of which were schizophrenic psychoses (n = 73). The other major diagnostic groups were adjustment or acute stress reactions, alcohol or drug dependence and personality disorders. The neurotic patients were generally older than the psychotic patients at the time of admission (p less than 0.02). More of them were married (62.7%) compared with the psychotics of whom 51.5% remained unmarried (p less than 0.02). Comparison between neurotic depressives and manic-depressive psychotics should have no difference in sex ratio and marital status. However, the duration of admission for the latter was longer. PMID- 1883179 TI - High frequency oscillatory ventilation in neonates with respiratory distress. AB - High frequency oscillatory ventilation (HFOV) was attempted in ten infants with severe respiratory failure not responding to conventional ventilation (CV); it was, therefore, used as a rescue measure. HFOV was successful in improving the respiratory status of seven infants, all with hyaline membrane disease (HMD). Five of these infants survived, of the remaining two, one died of massive peri/intra-ventricular haemorrhage and the other of cholestasis associated with total parenteral nutrition. It was unsuccessful in three infants, one with meconium aspiration, the second died within two hours commencing HFOV and the third with severe depression and hypotonia. PMID- 1883180 TI - Botulinum toxin in the treatment of facial dyskinesias. AB - Patients with hemifacial spasm (N = 25), blepharospasm (n = 8), and benign eyelid fasciculation (n = 2) were treated with botulinum toxin injections (PHLS, Porton Down, England). All patients reported substantial symptomatic relief. Marked improvement was seen in fifteen patients with hemifacial spasm and six patients with blepharospasm. Benign eyelid fasciculation was completely abolished. Beneficial effects was evident two to three days after injections, became maximum at one week, and remained effective for up to six months. Side effects were transitory and mild. They included periorbital edema, mild diplopia, ptosis and facial weakness. Only in two patients was ptosis unacceptable. Severity of side effects was dose-related. Reinjections had similar efficacy. Botulinum toxin therapy is a safe and effective treatment for these facial dyskinesias and should be considered a viable alternative to surgical procedures. PMID- 1883181 TI - Myocardial revascularisation in patients with carotid artery disease. AB - From January 1987 to December 1989, 80 patients with carotid bruit and/or history of transient ischaemic attack/stroke underwent digital subtraction angiography (DSA) prior to consideration for coronary artery bypass graft. Thirty-eight patients (Group I) out of the 80 had coronary artery bypass graft done with postoperative stroke in five (13.2%); this contrasted with a group of 320 patients (Group II) without cerebrovascular disease who underwent coronary artery bypass graft during the same period with postoperative stroke in two cases (0.63%) (p less than 0.0005). Carotid artery stenosis was noted on the DSA in 66% of Group I patients, with significant disease (greater than 70% occlusion) in 15%, while the study was normal in 34% of cases. Combined carotid endarterectomy and coronary artery bypass graft was done in five of Group I patients, with postoperative stroke in one; this was the only one among the stroke patients with significant carotid disease. All strokes, except in one patient, resolved within one to 6 1/2 months. These results suggest that the risk of stroke after coronary artery bypass graft is increased in patients with carotid bruit or history of transient ischaemic attack/stroke and in the presence of established carotid artery disease. The place of combined carotid endarterectomy and coronary artery bypass graft in these cases remains to be determined. PMID- 1883182 TI - Clearance of neonatal antiHBc following hepatitis B vaccination: relationship to antiHBs levels. AB - The persistence of antiHBc following hepatitis B virus (HBV) infection is sometimes regarded as evidence of a past infection, and the antiHBc inhibition of T-cell cytotoxic killing of HBV may be one way of tolerance leading to the carrier state. A model for studying the possibility of an immune tolerance occurring in the human situation was to observe the natural clearance rate of total antiHBc in babies who have acquired naturally maternal transferred antibodies, and to compare antiHBcIgG clearance and development of hepatitis B surface antigenaemia with the level of antibody to HBsAg (antiHBs), which is normally known to be virucidal. Two hundred and ninety-one normal infants who received hepatitis B vaccination in 1984 were followed and studied at six months, one, two and four years. AntiHBc was not found in any control infants born of HBsAg negative mothers. One child became antiHBc positive at four years reflecting acquired infection when antiHBs level had fallen to 36 mIU per ml. AntiHBc cleared in 66% of HBsAg pos./'e' neg. children at one year and completely by two years. In contrast, antiHBc clearance in children born of HBsAg pos./'e' pos. was inversely related to the antiHBs levels. Those with antiHBs levels over 50 mIU per ml cleared antiHBc more rapidly and were HBsAg negative, whereas in 28/49 (57%) HBs antigenaemia were associated more often with antiHBs under 10 mIU per ml and in 2/43 (5%) at levels between 11 to 50 mIU per ml. Two children who had later developed HBs antigenaemia in the presence of antiHBs after responding to earlier passive-active immunisation, suggest either defective antiHBs and/or the development of mutants or variants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883184 TI - Perineal eruption as an early sign of Kawasaki disease. AB - Kawasaki Disease can present as a diagnostic problem at the early stage of the disease. An interesting and distinctive perineal eruption which appeared early in the course of the disease had been reported recently but sporadically in the medical literature. We reported seven patients with Kawasaki Disease who had this perineal eruption. The rash began two to three days after the onset of fever followed by desquamation in all instances by days five to seven. When compared with other signs of Kawasaki Disease, this rash appeared early. In an earlier study done in the department, the diagnosis of Kawasaki Disease was made on an average of nine days after the onset of fever. This has an important implication as early treatment had been shown to decrease the incidence of coronary arteriectasia which is the most important complication of this disease. We believe that this distinctive perineal eruption is a valuable early clinical finding which may facilitate early diagnosis and treatment of Kawasaki Disease and unless one is aware and actively looked for the perineal eruption, this early sign may be completely missed. PMID- 1883183 TI - Neonatal listeriosis in Scotland. AB - Thirty-one cases of neonatal listeriosis occurred in Scotland between 1 January 1987 and 31 August 1989. In each of these, Listeria monocytogenes was cultured from blood, cerebrospinal fluid or both. No case of neonatal listeriosis occurred between 1 September 1989 and 31 July 1990, a statistically significant difference in incidence (p less than 0.001). A possible explanation may be that pregnant women adjusted their diet in accordance with the advice given by the Chief Medical Officer in his letter to General Practitioners of February 1989 entitled 'Food and Listeriosis'. Full clinical features and outcome of nineteen of the thirty-one cases were obtained from the paediatricians responsible for their care. Of these, sixteen were early onset and three late onset cases. There were eight deaths, all early onset cases. Two severely asphyxiated infants could not be resuscitated and of the five infants who required assisted ventilation from birth, four died. Four early onset and three late onset cases presented with pyogenic meningitis and all seven recovered without sequelae. It is concluded that when neonatal listeriosis presents as an asphyxiated infant who, after resuscitation, requires assisted ventilation, a fatal outcome is probable. When neonatal listeriosis presents as pyogenic meningitis, recovery without sequelae is the usual outcome. PMID- 1883185 TI - Location of valves and competence of the great saphenous vein above the knee. AB - The exact location of the valves of the great saphenous vein and the ability of these valves to prevent centrifugal flow were studied in 20 human cadaveric legs. A valve was present at the saphenofemoral junction in 17/20 (85%) legs. The great saphenous vein above the knee had 4.2 +/- 1.5 (mean +/- SD) valves. In a length standardised great saphenous vein which measured 100 units from the saphenofemoral junction to the knee joint line, the first, second, third, fourth and fifth valves were located at 7.5 +/- 3.6; 34.3 +/- 18.5; 61.0 +/- 20.9; 79.3 +/- 17.6; and 83.0 +/- 15.9 units from the junction respectively. 19/20 (95%) of the veins were competent at a centrifugal pressure of 161 +/- 7 cm of saline. PMID- 1883186 TI - An evaluation of the polymerase chain reaction for detection of alpha-globin genes in the prenatal diagnosis of alpha zero-thalassaemia. AB - Homozygous alpha zero-thalassaemia results in the fatal disease Bart's hydrops foetalis and since 3-4% of Singaporeans carry the alpha-thalassaemia genes, prenatal diagnosis of thalassaemia is essential. The aim of this study was to establish the polymerase chain reaction (PCR), a method that enables selective amplification of the 136 base pair (bp) region within the alpha-globin gene cluster, as a routine test for the prenatal diagnosis of homozygous alpha zero thalassaemia. Confirmation of PCR results was performed using DNA gene mapping and electrophoresis of cord blood. DNA was extracted from 24 chorionic villi samples and the presence of the alpha-globin genes was determined by PCR. The results showed that the optimal number of amplifications for accurate diagnosis was 50 cycles. Homozygous alpha zero-thalassaemia was detected in four foetuses and the pregnancies terminated. Confirmation of alpha zero-thalassaemia by DNA gene mapping and electrophoresis of cord blood showed absence of alpha-globin genes and only Hb Bart's respectively. The remaining 20 foetuses were correctly diagnosed as normal or possessing the alpha-thalassaemia trait. Using the PCR at less than 50 cycles of amplification (example 35 cycles), false positive results were obtained in 30% of cases. We conclude that DNA amplification using the PCR offers an accurate method of prenatal diagnosis of alpha zero-thalassaemia. Its advantages over the more establish gene mapping method include a more rapid analysis (three days compared with ten days by gene mapping) and the requirement of only minute amounts of DNA (1 microgram) for analysis. It is however, essential that the optimal number of amplification cycles be established so that false positive results may be avoided. PMID- 1883187 TI - Safety of surgery in elderly. AB - The problem of surgery in an increasingly ageing population worldwide is reviewed. The outcome in a prospective study of 505 patients admitted to a general surgical unit is considered and the risks determined. The factors leading to poor results such as emergency surgery, multiple operations, duration of operation, age itself and the physical status of the patient are examined and evaluated. The overall mortality rate in the study was 14.5%, with 12% for major operations, 6.1% for minor procedures and 24.3% for those who had no operation. The unsatisfactory nature of existing systems of audit are discussed and a new system of audit is proposed which takes into account and defines the 'non-viable' and the 'potentially viable' patient. When this system was applied to the study there was a significant drop in the overall mortality from 14.5% to 3.6%, from 12.0% to 5.8% for major operations, from 6.1% to 0% for minor operations and from 24.3% to 2.0% for those with no surgery. Finally recommendations are made to improve the safety of surgery in the elderly. PMID- 1883189 TI - Thyroid eye disease--medical or surgical therapy? AB - Thyroid eye disease is autoimmune in nature and associated with Graves' Disease. Autoantibodies to the 64 kDa antigen in thyroid membranes cross-react to the 64 kDa proteins in human eye muscle membranes. Antibody dependent cell mediated cytotoxicity against eye muscle cells are also found in patients with thyroid eye disease. The purpose of this paper is to review the treatment available and to share the authors' experience using cyclosporin A. In the majority of cases, thyroid eye disease is mild, manifest only as bilateral or unilateral proptosis, with/without grittiness of the eyes. This is usually treated conservatively with eye drops. If proptosis is more severe and there is incomplete closure of eyelids, epiphora and conjunctival injection, then lateral tarrsorrhaphy is usually effective, combined with use of eye pads and eye drops. The problem of diplopia can be treated conservatively with special lenses, or with surgical correction of tethered muscles. However when proptosis is severe, with raised intraocular pressure, severe chemosis and danger of blindness, then the choice of therapy is controversial: rapid decompression by surgical means or use of high doses of prednisolone. Most prefer prednisolone therapy initially, surgical decompression if it fails. Various other methods have been tried, aimed at the immunological nature of the disease, namely plasmapheresis, radiotherapy and immunosuppressive drugs such as cyclosporin, with variable success. Our experience with cyclosporin had been mixed and inconclusive. PMID- 1883188 TI - Gastrointestinal infections in Singapore children. AB - Acute gastroenteritis is the commonest gastrointestinal disorder in children. It accounted for about 10% of the admissions to a general paediatric unit in Singapore. About 5% of total paediatric admissions to all the government hospitals in Singapore were due to acute gastroenteritis. Some 50% of the cases had no identifiable organism in the stools. Most of the remaining cases were due to bacterial or viral infections. The commonest bacteria responsible for acute gastroenteritis nowadays is Salmonella species. Other bacteria such as E. coli, Shigella and Campylobacter were responsible for a smaller proportion of bacterial diarrhoea in children. Rotavirus was the commonest viral agent responsible for acute diarrhoea among Singapore children. Most patients had mild diarrhoea and severe dehydration following acute gastroenteritis was not common. About 60% of the patients admitted to hospital were younger than two years of age. Bacterial infections were more common in infancy. Viral diarrhoea were more likely to be watery and bacterial diarrhoea were more likely to be bloody and mucoid. With regard to chronicity, it was the groups with mixed infection or bacteria infection which had a prolonged course. Treatment was directed at maintaining hydration and prevention of complications. Except for secondary lactase deficiency, other long term complications were rare. PMID- 1883190 TI - Developing trends in clinical computing. AB - With the emergence of personal computers and graphical interfaces during the 1980s, advanced computational power has at last become accessible and affordable for practising clinicians in both inpatient and outpatient settings. Many observers have accordingly noted the relatively low level of direct computer use by physicians in their practices. This paper summarises developing trends in clinical computing, emphasising the role of local and wide-access networks, the revolutionary potential of optical storage techniques, and the notion of integrated workstations that will bring a critical mass of diverse functions to the physician. An important lesson of this review is the current availability of most of the technologies needed for high-quality and acceptable clinical computing tools. The barriers to successful implementation tend to be logistical, financial, and political. Despite these obstacles, new technologies, coupled with educational efforts, should allow the computer to emerge as a crucial aid to clinicians in the decade ahead. PMID- 1883191 TI - Mechanical symptoms arising from synovial pathology in knee joint. AB - Synovial pathology is a rare cause of mechanical symptom in the knee joint. The clinical features, arthroscopic appearance and histology of Hoffa's syndrome and localised villonodular synovitis are discussed. PMID- 1883192 TI - The Runme Shaw Memorial Lecture--transplantation of the heart and heart-lungs. AB - After ten years of experimental background, the first heart transplant at Stanford was performed on January 6, 1968. Six hundred and sixty-six patients have undergone 721 heart transplants since that date with an age range from five days to 64 years. The most common diagnosis has been cardiomyopathy with advanced coronary artery disease second. Current one and five year survival statistics are 81% and 60% respectively, with no difference in survival between the pediatric age group and adults. Percutaneous transvenous endomyocardial biopsy provides the gold standard for interpreting allograft rejection. At Stanford, 90 patients have undergone 91 heart-lung transplants since the first successful case in 1981. Twelve patients with cystic fibrosis have been transplanted and four of these recipients have been heart donors, the domino donor principle. Two double lung transplants have been performed utilising separate bronchial anastomoses. Fourteen patients have undergone 15 single lung transplants and three of these have been patients with the Eisenmenger syndrome where concomitant repair of the cardiac defect was carried out. One 12 year old patient received the right upper lobe of her mother as a total right lung transplant for bronchopulmonary dysplasia. PMID- 1883193 TI - The Peter Lowe Lecture--medicine in the 1990s. AB - This paper set out to examine the role of medicine and medical practice. It has done so by posing a series of questions related to the role of the doctor, health and health care, and the patient-doctor relationship. One of the objectives was to re-examine some of the principles of medical practice, another to consider a vision of medicine for the future. The result of this examination has not turned up anything particularly new or original. What it has done, I believe has been to endorse the principles of medicine which have been established for thousands of years. Yet perhaps in some ways they need to be re-asserted and discussed afresh. Because of the enormous changes in society, in health care and the external and internal pressures on doctors, such values can be forgotten or lost. Change is inevitable and doctors must adapt to meet the changes. They must do so in a positive way and wherever possible take the lead in shaping the health and health care of the future. The values of the future are those of the past, though the setting and context may be quite different. These values include, the importance of caring, the central role of communication, the need to be involved in health as well as illness, the implications of making a diagnosis and the fundamental nature of education and training. There is a need to retain common sense and perspective in making decisions. My vision of the future of medicine is therefore clear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883194 TI - 50 years of biological research--from oxidative phosphorylation to energy requiring transport regulation. AB - In 1930 adenosine triphosphate appeared in the literature from W. A. Engelhardt's work on avian erythrocytes. This was an early example of oxidative phosphorylation in intact cells, and it required methylene blue and oxygen. Both Belitser and I realized that the use of Warburg manometers for aeration was critical in order to generate oxidative phosphorylation of glucose in tissue preparations. Test tube techniques did not work. In 1956 we were able to describe a human type of diabetes called "galactose diabetes," in which consumption of human or cows' milk provokes mental retardation. Replacement of human or cows' milk products with "vegetable milk" formula in early infancy can prevent retardation. We determined that the disease results from a defect of galactose one-phosphate uridylyl-transferase, a hereditary enzyme. This type of enzyme defect, if discovered and treated in early infancy, is a benign molecular disease. Regulation of transport systems in mammalian cell cultures are frequently complex energized systems. Perhaps my greatest surprise in this regard was the mere fact that an all-cis "odd" hexose-D-allose turned out to be a highly intense down-regulator of the hexose transport system. Additions of inhibitors of oxidative phosphorylation (such as oligomycin or di-nitrophenol) arrested the allose-mediated down-regulation. We have reason to suspect that the strong down regulator is a phosphorylated form of D-allose. Thus ends my story about oxidative energized biological phosphorylation systems. PMID- 1883195 TI - Cell adhesion molecules: implications for a molecular histology. PMID- 1883196 TI - Ribosomal RNA and translation. PMID- 1883197 TI - Lysosomal storage diseases. PMID- 1883198 TI - Primary response genes induced by growth factors and tumor promoters. PMID- 1883199 TI - Protein-priming of DNA replication. PMID- 1883200 TI - Signal transduction pathways involving protein phosphorylation in prokaryotes. PMID- 1883201 TI - Proteoglycans: structures and interactions. PMID- 1883202 TI - Fidelity mechanisms in DNA replication. PMID- 1883203 TI - Eukaryotic DNA polymerases. PMID- 1883204 TI - The biochemistry of AIDS. PMID- 1883205 TI - RNA polymerase II. PMID- 1883206 TI - Translational control in mammalian cells. PMID- 1883207 TI - Phospholipid transfer proteins. PMID- 1883208 TI - Structure and function of hexose transporters. PMID- 1883209 TI - Denatured states of proteins. AB - The denatured "state" of a protein is a distribution of many different molecular conformations, the averages of which are measured by experiments. The properties of this ensemble depend sensitively on the solution conditions. There is now considerable evidence that even in strong denaturants such as 6M GuHC1 and 9M urea, some structure may remain in protein chains. Under milder or physiological conditions, the denatured states of most proteins appear to be highly compact with extensive secondary structure. Both theoretical and experimental studies suggest that hydrophobic interactions, chain conformational entropies, and electrostatic forces are dominant in determining this structure. The denaturation reaction of many proteins in GuHC1 or urea can be most simply modelled as a two state transition between the native structure and a relatively compact denatured state, which then undergoes a gradual increase in radius on further addition of denaturant. However, when a protein acquires a large net charge in acids or bases, it can have two stable denatured populations, one compact and the other more highly unfolded. The prediction and elucidation of the structural details of the non-native states of proteins may ultimately prove to be as difficult as predicting the native structures, particularly for D0, the denatured state under physiological conditions. Just as with the native state, the structure of this biologically important denatured state appears to depend on the amino acid sequence. The development of synthetic, peptide and protein fragment models of the denatured state and the recent progress in NMR spectroscopy provide bases for optimism that new insights will be gained into this poorly understood realm of protein biochemistry. PMID- 1883210 TI - The regulation of histone synthesis in the cell cycle. PMID- 1883212 TI - Malignant lymphomas in patients with HIV infection in Italy. PMID- 1883211 TI - Kaposi's sarcoma in Italy, a country with intravenous drug users as the main group affected by HIV infection. PMID- 1883213 TI - Review of epidemiology of HIV-1 infection in children: Zaire experience. PMID- 1883215 TI - AIDS and hemophilia. PMID- 1883214 TI - Pediatric AIDS and associated cancers in Kinshasa, Zaire. PMID- 1883216 TI - Update on AIDS opportunistic infections. PMID- 1883217 TI - Classification of histopathological changes of lymph nodes in HIV-1 infection. Significance of Castleman's disease-like lymph node lesion concerning the diagnosis of HIV-1-related Kaposi's sarcoma. PMID- 1883218 TI - Functional brain imaging in AIDS-related dementia: a review. PMID- 1883219 TI - New therapeutic approaches in the acquired immune deficiency syndrome. PMID- 1883220 TI - An international perspective on organizing people at risk for AIDS at the community level. PMID- 1883221 TI - The future impact of AIDS on society. PMID- 1883222 TI - Biomedical and social considerations on the AIDS pandemic and associated tumors. PMID- 1883224 TI - Drug addiction and AIDS. PMID- 1883223 TI - AIDS and drugs in Amsterdam: prevention measures. PMID- 1883225 TI - HIV-associated malignancies. PMID- 1883226 TI - Prospected etiopathogenic mechanisms of AIDS-associated tumors. PMID- 1883228 TI - Biochemical studies carried out on different groups of Candida parapsilosis and Candida rhagii strains by comparing some cellular and mitochondrial activities. AB - A comparative biochemical study was performed on some strains of Candida rhagii and on strains belonging to different subgroups of Candida parapsilosis. Measurements of alcohol dehydrogenase activity, resistance to drugs and occurrence of an alternative pathway enabled us to confirm the classification between several subgroups within the C. parapsilosis species. PMID- 1883227 TI - Changes in pulmonary surfactant during bacterial pneumonia. AB - In pneumonia, bacteria induce changes in pulmonary surfactant. These changes are mediated by bacteria directly on secreted surfactant or indirectly through pulmonary type II epithelial cells. The bacterial component most likely responsible is endotoxin since gram-negative bacteria more often induce these changes than gram-positive bacteria. Also, endotoxin and gram-negative bacteria induce similar changes in surfactant. The interaction of bacteria or endotoxin with secreted surfactant results in changes in the physical (i.e. density and surface tension) properties of surfactant. In addition, gram-negative bacteria or endotoxin can injure type II epithelial cells causing them to produce abnormal quantities of surfactant, abnormal concentrations of phospholipids in surfactant, and abnormal compositions (i.e. type and saturation of fatty acids) of PC. The L/S ratio, the concentration of PG, and the amount of palmitic acid in PC are all significantly lower. The changes in surfactant have a deleterious effect on lung function characterized by significant decreases in total lung capacity, static compliance, diffusing capacity, and arterial PO2 and a significant increase in mean pulmonary arterial pressure. Also decreased concentrations of surfactant or an altered surfactant composition can result in the anatomic changes commonly seen in pneumonia such as pulmonary edema, hemorrhage, and atelectasis. PMID- 1883229 TI - Pyrimidine base and ribonucleoside utilization by the Pseudomonas alcaligenes group. AB - Pyrimidine base and ribonucleoside utilization was investigated in the two type strains of the Pseudomonas alcaligenes group. As sole sources of nitrogen, the pyrimidine bases uracil, thymine and cytosine as well as the dihydropyrimidine bases dihydrouracil and dihydrothymine supported the growth of Pseudomonas pseudoalcaligenes ATCC 17440 but neither these bases nor pyrimidine nucleosides supported Pseudomonas alcaligens ATCC 14909 growth. Ribose, deoxyribose, pyrimidine and dihydropyrimidine bases as well as pyrimidine nucleosides failed to be utilized by either P. pseudoalcaligenes or P. alcaligenes as sole carbon sources. The activities of the pyrimidine salvage enzymes nucleoside hydrolase, cytosine deaminase, dihydropyrimidine dehydrogenase and dihydropyrimidinase were detected in cell-free extracts of P. pseudoalcaligenes and P. alcaligenes. In P. pseudoalcaligenes, the levels of cytosine deaminase, dihydropyrimidine dehydrogenase and dihydropyrimidinase could be affected by the nitrogen source present in the culture medium. PMID- 1883231 TI - Karyology and the possible function of the dual conidia of Dissoconium (Hyphomycetes). AB - The morphological development and nuclear behaviour of two species of Dissoconium are described. The fungi are monokaryotic in all stages of their life cycle. Liberated pairs of conidia may form anastomoses, probably serving survival under hostile environmental conditions. The function of the one-celled conidia in D. dekkeri remains unexplained. PMID- 1883232 TI - Fellomyces horovitziae sp. nov., a new basidiomycetous yeast species isolated from a Xenasmatella basidiocarp. AB - A new species of the genus Fellomyces, F. horovitziae, was isolated from a Xenasmatella basidiocarp. It differs from other accepted species in its carbon assimilation pattern, mol% G + C and low DNA-DNA homology. The delimiting characters are discussed and a key to the genus is provided. PMID- 1883230 TI - Physiological aspects of growth and recombinant DNA stability in Saccharomyces cerevisiae. AB - Despite the fact that plasmid stability in the yeast Saccharomyces cerevisiae is influenced by both genetical and physiological parameters most attention has been focused on the former. Physiological factors affecting the stability of plasmids have been poorly characterized despite the need for such information in order to optimize the use of S. cerevisiae as a host for recombinant protein production processes. The physiology of wild type S. cerevisiae differs considerably when grown using different cultivation techniques. A limited amount of phenomenological data has been reported concerning plasmid instability effects under these different conditions and in this article these have been collected together with the intention of providing an overview to instability effects and to try and propose reasons as to how the physiological response to different growth conditions can be manifested as stability/instability effects. PMID- 1883234 TI - Orthopedists urged to curtail surgeries. PMID- 1883233 TI - Issues surrounding intravenous conscious sedation. PMID- 1883235 TI - Aging research and its influences on health care. PMID- 1883236 TI - Pharmacodynamics of parenteral antiarrhythmic agents. PMID- 1883237 TI - The OR supervisor's responsibilities in reducing liability. PMID- 1883239 TI - Camey procedure. A continent urinary diversion technique. PMID- 1883238 TI - Fetal surgery. In utero repair of congenital diaphragmatic hernia. PMID- 1883240 TI - Dupuytren's contracture. Surgical principles, nursing implications. AB - Successful Dupuytren's surgery requires the cooperation of the patient, the surgeon, and the therapist. Cooperation of the patient is enhanced by nursing care. Preoperative and postoperative teaching by the nurse also contribute to positive outcomes. The type of incision or surgery performed does not affect the time of recovery if the diseased tissue is removed and there are no postoperative complications. PMID- 1883241 TI - Insulin-dependent diabetes. Its effect on the surgical patient. AB - Physicians and nurses need to be aware of the metabolic needs of the diabetic patient and incorporate those requirements into the plan of care during the perioperative period. With appropriate management, morbidity and mortality rates for diabetic patients who undergo surgery may approach those for the nondiabetic population. PMID- 1883243 TI - HIV studies target women. PMID- 1883242 TI - Proposed recommended practices. Disinfection. AORN Recommended Practices Coordinating Committee. PMID- 1883244 TI - Proposed recommended practices. Sterilization. AORN Recommended Practices Coordinating Committee. PMID- 1883245 TI - Surgical case acuity. OR managers' perceptions. PMID- 1883246 TI - A spontaneous increase of salt intake and changes of colonic temperature in mice exposed to cold. AB - The effect of repeated short-term exposure to cold on spontaneous salt (NaCl) intake and colonic temperature was investigated in two experiments on mice. In Experiment 1, half of a group of test animals were exposed to cold (7-9 degrees C; 6h/day; 4 days), and half of both the exposed and non-exposed animals were allowed to choose between drinking water with (0.9%) and without (0%) NaCl. Food and fluids were provided all day long during the experiment. Mice provided with NaCl solution showed increased salt intake with cold exposure. Colonic temperature of mice was measured twice a day at the beginning and the end of cold exposure. Different changes in colonic temperature among the groups were observed at the end of cold exposure. In mice exposed to cold and provided with NaCl solution, colonic temperatures stayed unchanged, whereas in those without NaCl solution colonic temperatures decreased significantly after cold exposure. In Experiment 2, all the mice were exposed to cold as in Experiment 1. Four patterns of feeding of food and fluids were applied to groups of eight mice each: removal of food and fluids during cold; removal during 9 h before cold and during cold; removal during cold and during 9 h after cold, and feeding all day long. Half the mice in each feeding pattern were allowed to choose NaCl fluids (0% & 0.9%). Colonic temperature was measured as in Experiment 1. In all the feeding patterns, colonic temperature was significantly lower in the mice without NaCl solution than those with NaCl solution. Among four feeding patterns in mice with NaCl solution, colonic temperature was significantly higher in the case of feeding all day long than in the other three patterns. PMID- 1883247 TI - Transient and lasting effects of reproductive episodes on NaCl intake of the female rat. AB - Following recovery from experimental sodium depletion, both the need-free and the future need-induced NaCl intakes of the rat are increased. The present experiments asked whether a naturally occurring episode of sodium need, pregnancy and lactation, would also enhance NaCl intake. The daily 0.3 M NaCl intake of Long-Evans rats increased from 18.2 ml (prior to pregnancy) to 28.7 ml during pregnancy, and increased further to 36.2 ml during lactation. The daily intakes remained increased after the weaning of the second litter, at 28.5 ml/24h for females which had access to 0.3 M NaCl during the reproductive episodes (DAM + Na) and at 27.6 ml/24h for those which did not (DAM). When they were subsequently sodium depleted, the need-induced NaCl intake of the DAM, but not the DAM + Na group, was significantly increased compared to virgin female rats. The sodium depletion-induced water intakes of both groups were significantly increased. Neither the need-free nor the need-induced intakes of their offspring (as adults) were increased. In summary, pregnancy and/or lactation, in the absence of a sodium deficit, produced increased intakes of NaCl which persisted beyond the reproductive episodes. PMID- 1883248 TI - Neophobia in humans and the special status of foods of animal origin. AB - Research from the anthropological, psychological, and animal behavior literatures suggests that foods of animal origin have a special status. In two studies we explored the question of whether individuals are more neophobic with respect to animal foods than non-animal foods. In the first study male and female subjects, after reading descriptions, rated their willingness to taste ten "novel" foods, which were actually fictitious. Foods in meat/fish/poultry and dairy/egg categories received lower ratings than those in fruit, vegetable, and grain categories. In the second study subjects were exposed to real foods, some of which were named and described accurately and were, therefore, familiar and some of which were named and described fictitiously and were, therefore, novel. There were no food category differences in subjects' willingness to taste familiar foods, but subjects were less willing to eat novel flesh foods than foods in the other categories. The results are discussed in terms of Rozin & Fallon's (1980) taxonomy of motivations for rejecting foods. PMID- 1883249 TI - Temporal patterns of hunger and fullness ratings and related cognitions in anorexia and bulimia. AB - Hunger and fullness during an experimental liquid meal were evaluated by ratings in 84 eating-disordered patients, including three diagnostic subgroups, and in 19 controls who were normal in weight and eating healthily. Anorectic-restrictors had lower hunger ratings and higher fullness ratings than controls. The same tendency was present in anorectic-bulimics. These ratings were relatively unaffected by treatment. Anorectic-restrictors had longer meals than the anorectic-bulimics and normal-weight bulimics. The anorectic-restrictors also tended to eat more slowly than did the bulimic patients. These groups did not, however, differ in amount consumed. At the end of the experimental meal, the anorectic-bulimics were more preoccupied with thoughts of food and anorectic restrictors had a lower urge to eat, as compared with the controls. Hunger and fullness ratings were negatively correlated for all diagnostic groups; however, these correlations were less pronounced for the eating disorder groups. The eating-disordered patients had predominantly "abnormal" patterns of hunger and fullness curves, indicating a confusion of these concepts. PMID- 1883250 TI - What should you eat? A survey of south Australian women's food consumption norms. AB - In a random population survey, 418 South Australian women rated the desirability of consumption of 48 common foods, according to their perceived health relevance. Multidimensional scaling of the women's responses yielded three dimensions which accounted for 87% of total variance. The first two dimensions were related to healthiness (low fat, salt and sugar contents) and traditional-artificial nutrient-reduced foods respectively. Younger women rated healthy foods more highly. The mean ratings also formed a unidimensional scale which had high internal reliability (Cronbach's alpha = 0.80). These unidimensional scores were correlated with reported food intakes of a random sample of respondents in the State of Victoria, using mean values for demographic subgroups (r = 0.50). The results suggest that food intake, or alternatively recalls of food intake, may be influenced by such prescriptive norms. PMID- 1883252 TI - Recognition, management, and course of anxiety and depression in general practice. AB - This article addresses the issues of recognition of psychiatric disorders by general physicians (GPs) and the effects of recognition on management and course. Among 1994 patients who were screened with the General Health Questionnaire and who were rated by their GP, 1450 (72.7%) had not been identified by the GP as having a psychiatric disorder in the year before the index visit. Among these "new" patients, 557 (38.4%) had positive General Health Questionnaire scores. Only 47% of the new patients who met Bedford College diagnostic criteria for anxiety, depression, or ill-defined disorder had their psychiatric disorder recognized by their GP. Among patients who met Bedford College criteria, mean episode durations were longer for anxiety disorders (20 to 22 months) than for depressive disorders (9 to 10 months). Among the new patients, those with psychiatric disorders recognized by the GP were more likely to receive mental health interventions. Recognition was associated with shorter episode duration among patients with an anxiety disorder, but not among patients with depressive or ill-defined disorders. PMID- 1883251 TI - Lower pleasantness of palatable foods in nalmefene-treated human volunteers. AB - The involvement of endogenous opioids in control of human food intake and appetite was investigated in a double-blind placebo-controlled study using a single, 2.5 mg oral dose of the opioid receptor antagonist, nalmefene. Ratings of the pleasantness of the smell and the taste, but not the appearance, of a number of foods was significantly lower in nalmefene-treated subjects. The magnitude of this effect was greater in food items independently rated as highly palatable. Caloric intake of a buffet-style meal was 20% lower in nalmefene-treated subjects, with the proportional reduction in intake of individual food items also depending on their palatability. These results lend further support to recent suggestions that opioids are involved in reward-related aspects of ingestion. PMID- 1883253 TI - Explicit memory and repetition priming in depression. Preliminary findings. AB - Explicit memory and repetition priming, a form of implicit memory, were examined in depressed patients and controls. Explicit memory of depressed patients was severely impaired, whereas repetition priming was intact. These results are consistent with the hypothesis that the impairment of memory in depression is linked to a failure of effort-demanding cognitive processes. Repetition priming might be useful in differentiating between depression and dementia. PMID- 1883254 TI - Comorbidity of psychiatric diagnoses in anorexia nervosa. AB - The comorbidity of psychiatric diagnoses was examined with the Diagnostic Interview Schedule in 62 women who participated in a 10-year follow-up study of anorexia nervosa. Sixty-two age- and sex-matched controls, their parents, and parents of the anorectic probands were also interviewed with the Diagnostic Interview Schedule. There was a statistically significant comorbidity of the affective and anxiety disorders with anorexia nervosa. The first-degree relatives of the anorectic probands had significantly more alcoholism and total number of psychiatric diagnoses compared with the first-degree relatives of controls. There were two mothers with bulimia nervosa, two cases of anorexia nervosa and two of bulimia nervosa in other first-degree relatives of anorectic probands, and no cases of eating disorders in the first-degree relatives of controls. PMID- 1883255 TI - Trait-state artifacts and the diagnosis of personality disorders. AB - The multiaxial nature of DSM-III has stimulated interest in the personality disorders. There are also indications that it has produced an increase in their diagnosis. However, there is clinical and psychometric evidence that a personality evaluation undertaken while a patient is in a dysphoric mental state may distort or misrepresent traits, the so-called trait-state problem in personality assessment. The present study appears to be the first to investigate this phenomenon with a clinical interview rather than with personality tests. It examined the effect of anxiety, depression, and level of global impairment on the diagnosis of personality disorder and the assessment of the criteria for the individual Axis II disorders. Eighty-four patients, most of whom had current Axis I diagnoses, were evaluated by seven experienced clinicians with a new semistructured interview, the Personality Disorder Examination. The sample evidenced a trend toward acknowledging fewer maladaptive personality traits at follow-up than at entry. There was no evidence, however, that anxiety or depression had affected either the diagnosis of a personality disorder or the criteria associated with most of the individual personality disorders. PMID- 1883256 TI - Clomipramine in the treatment of patients with obsessive-compulsive disorder. The Clomipramine Collaborative Study Group. AB - Two double-blind studies at 21 centers evaluated the therapeutic efficacy, safety, and tolerability of up to 300 mg/d of clomipramine hydrochloride or an equivalent number of placebo capsules in the treatment of 520 patients with obsessive-compulsive disorder, of whom 239 had had the disorder for at least 2 years (study 1) and 281 had been ill for at least 1 year (study 2). On the two principal measures of the severity of the disorder, ie, the Yale-Brown Obsessive Compulsive Scale and the National Institute of Mental Health Global Obsessive Compulsive Scale, clomipramine was significantly more effective than placebo in both studies. The mean reduction in the Yale-Brown Obsessive Compulsive Scale score at the end of 10 weeks of treatment was 38% and 44% in studies 1 and 2, respectively, for the clomipramine-treated patients and 3% and 5% for the placebo treated patients. The drug was also found to be superior on the basis of the physicians' and patients' evaluations of global therapeutic change. The most frequently observed adverse effects during clomipramine therapy were those typically associated with tricyclic antidepressant drugs. Although uncommon, the occurrence of seizures and elevated aminotransferase values are potentially serious side effects of clomipramine. Clomipramine was generally well tolerated and was effective in reducing obsessive and compulsive symptoms. PMID- 1883257 TI - Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose. AB - After individual determination of neuroleptic threshold (NT) doses of haloperidol, 106 patients with schizophrenia or schizoaffective disorder (Research Diagnostic Criteria) were treated openly at such doses (mean, 3.7 +/- 2.3 mg/d) for 2 weeks. Ten responding patients were discharged and unavailable for follow-up or refused subsequent randomization, and one non-responding patient refused randomization. The remaining 95 responding or nonresponding patients were then randomly assigned, double-blind, to a dosage of haloperidol two to 10 times higher (mean, 11.6 +/- 4.7 mg/d) or to a continuing NT dosage (mean, 3.4 +/- 2.3 mg/d) for another 2 weeks. Of the 58 patients exposed only to NT dosages of haloperidol, 72% clinically recovered within the 5-week trial. Higher dosages given to 47 patients did not lead to greater improvement in measures of psychosis, but did produce slightly greater declines in measures of hostility. Higher dosages did regularly lead to significant increases in distressing extrapyramidal side effects. PMID- 1883258 TI - Antidepressant effects of high-dose right unilateral electroconvulsive therapy. AB - In a random-assignment, double-blind, controlled comparison in 38 melancholic men, overall antidepressant potency of high-dose electroconvulsive therapy (378 mC charge) given with right unilateral electrode placement was not significantly different from that with bilateral placement, although there was a trend for faster improvement with bilateral ECT. The suprathreshold character of the stimulus, about 2.5 times the expected seizure threshold, may have contributed to the high efficacy of brief-pulse right unilateral electroconvulsive therapy found in this study. PMID- 1883259 TI - Characterizing organic delusional syndrome. AB - We present a first comprehensive description of the clinical features of patients with organic delusional syndrome. This description is based on information from 39 patients with organic delusional syndrome among 14,889 patients who presented for initial evaluation over a 5-year period at our institution. This description includes an enumeration of the common clinical symptoms of this syndrome and the respective prevalence and mean severity of each symptom. The severity of the symptoms of organic delusional syndrome are compared with those of schizophrenia to determine which symptoms distinguish between these two diagnostic categories. Patients with organic delusional syndrome demonstrated significantly more symptoms of "acquired intellectual impairment," "impaired sensorium," and "hallucinations of smell, taste, or touch," while schizophrenic patients demonstrated more "flat affect," "emotional coldness," and "thought disorganization." In addition, associated factors are presented concerning demographics, modes of treatment, level of functioning, and current physical problems associated with organic delusional syndrome. PMID- 1883260 TI - Academic medical center/industry collaboration. PMID- 1883261 TI - Association between the D2 dopamine receptor gene and alcoholism. A continuing controversy. PMID- 1883262 TI - A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. PMID- 1883263 TI - [Atopic dermatitis and eosinophils]. PMID- 1883264 TI - [Investigation of the genetics of allergic children, the second report--family study to determine the major gene in allergic disease using affected sib pair method]. AB - Twenty-six families with allergic siblings were investigated to define the mode of inheritance of asthma and DF specific IgE antibody production in children. The affected sib pair method was used to establish the linkage between disease susceptibility genes and HLA antigens. The affected sib pair method revealed that in asthmatic families chi 2 = 4.9 (no significance) and in DF-specific IgE positive families chi 2 = 6.2 (p less than 0.05). This study suggests that the gene of DF-specific IgE antibody production is linked to HLA haplotypes, but the mode of inheritance of DF-specific IgE antibody production couldn't be defined. PMID- 1883265 TI - [Studies on IgG subclass antibodies in adult asthma. 1. Serum antigen specific IgG subclass antibodies in asthmatics with late asthmatic response]. AB - It is clear that immediate asthmatic response is mediated by IgE-dependent mechanisms. However, late asthmatic response is induced by inhalation of antigens without antigen specific IgE antibodies in some asthmatics, especially in intractable asthma induced by Candida antigen. To elucidate the relationship between those bronchial responses and antibodies, antigen specific IgG subclass antibodies in sera from asthmatics were measured and compared with IgE antibody. The results were as follows. 1. Avidin-biotin ELISA (enzyme-linked immunosorbent assay) method was established for the measurement of specific IgG and IgG subclass antibodies to mite or Candida antigen. 2. Serum levels of antigen specific IgG and IgG1 antibodies in asthmatics with LAR provoked by mite or Candida antigen were significantly higher than those in asthmatics without LAR (p less than 0.01). 3. Serum levels of specific IgE antibody to these antigens in asthmatics with LAR provoked by mite or Candida antigen were slightly lower than those in asthmatics without LAR, though the difference is not significant. These results suggest that high serum levels of specific IgG and IgG1 antibodies to these antigens play a role in inducing LAR in asthmatics with LAR. PMID- 1883266 TI - [Positivities of skin test and IgE rast to allergens in bronchial asthma with normal serum IgE levels]. AB - The positivities of skin test and specific IgE antibodies were studied in 179 asthmatic patients who were divided into three groups according to their serum IgE levels: group L = less than 300 U/ml, group M = 300-700 U/ml, group H = greater than 700 U/ml. 1) The study population was made up as follows: group L 44%, M 28% and H 29%. 2) Skin test positivity was 35% in group L, 74% in M, 92% in H and 14% in the healthy non-asthmatic group. 3) The positivity in IgE RAST was 37% in L, 69% in M and 83% in H. 4) The percentage of patients showing positivity in either skin test or IgE RAST was 37% in L, 76% in M and 92% in H. These results suggest that we should be careful in determining the type of asthma in case of normal serum IgE level. PMID- 1883267 TI - [Detection and analysis of IgG antibodies in sera of patient with atopic dermatitis (AD) to individual wheat polypeptides by immunoblotting techniques]. AB - To detect IgG antibodies in sera of patients with atopic dermatitis (AD) to individual wheat polypeptides, wheat flour proteins were extracted with tris citrate buffered saline containing urea and 2-mercaptoethanol (UTC solvent), and fractionated as polypeptides of molecular weights between 12 and 100 KDa. By means of the immunoblotting techniques, specific IgG antibodies to fractionated proteins could be detected in sera from healthy individuals and AD patients. Twenty AD patients' sera with high titers of wheat specific RAST (scores of more than 3) reacted not only to five major wheat components (33-38, 40-45, 55-60, 80, 90-98 KDa), which stained intensively with Coomassie brilliant blue G-250, but also to polypeptides of 14, 16, 22, 29, 70 KDa. Twelve control sera reacted to a limited number of the five major wheat components, and levels of specific IgG antibodies increased with age. The sera of AD patients in the present study contained increased level of IgG antibodies to the five major components, and additionally to several minor components, 70 KDa, 29 KDa and much smaller proteins. PMID- 1883268 TI - [The effect of AH 21-132 on airway hyperresponsiveness induced by ozone exposure]. AB - We examined the effect of AH 21-132, which has been reported to relax airway smooth muscle and inhibit platelet activating factor (PAF)-induced airway hyperreactivity, on ozone-induced airway hyperresponsiveness (AHR) with airway inflammation in dogs. Airway responsiveness (AR) to methacholine was measured by modified Astograph (7 Hz oscillation method) before and after ozone exposure, and the numbers of neutrophils in the peripheral blood and total cell counts, differential cell counts and TXB2 in BALF were measured before and after ozone exposure. Ozone exposure was carried out for 2 hr at an ozone level of 3.46 +/- 0.10 ppm (mean +/- SE). There was a significant increase in AR to methacholine after ozone exposure (p less than 0.01), and the numbers of neutrophils in the peripheral blood and the total cell and neutrophil counts in BALF increased significantly (p less than 0.05). Pretreatment with AH 21-132 at an oral dose of 20 mg/kg significantly prevented the ozone-induced AHR to methacholine (p less than 0.01), and also inhibited the increase of neutrophil counts in the peripheral blood, and the total cell counts and the neutrophil counts in BALF after ozone exposure. There was no significant change in the levels of TXB2 in BALF before and after ozone exposure. In dogs not exposed to ozone, AR to methacholine and respiratory resistance to methacholine significantly decreased after administration of AH 21-132 at an oral dose of 20 mg/kg (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883269 TI - [Bronchial hyperresponsiveness to histamine following antigen challenges in actively sensitized guinea pigs]. AB - Guinea pigs were actively sensitized by intraperitoneally administered ovalbumin and challenged by intravenous injections of ovalbumin. Respiratory resistance and dynamic compliance were measured by pulmonary mechanics analyzer Buxco Model 6. Changes in resistance (delta R) and compliance (delta C) induced by intravenously administered histamine were investigated before and after the challenge. Responses to the histamine in sensitized guinea pigs were also compared with those in naive guinea pigs. The following results were obtained. 1) A significant increase in delta R by histamine administration was observed following the antigen challenge. delta C by histamine administration showed a tendency to increase after the challenge. 2) A significant increase of delta R by 7.2 micrograms/kg histamine administration was observed in actively sensitized guinea pigs. However, delta C by the histamine administration did not change in the sensitized animals. PMID- 1883270 TI - [Evaluation of new system for the detection of IgE antibodies (CAP) in atopic diseases]. AB - An evaluation of a newly developed IgE antibody assay system (CAP) was carried out. There was a clear correlation between IgE antibody titers measured by CAP single and RAST (= 0.642 to 0.979). It turned out that CAP single is more sensitive than RAST and non-specific adsorption of IgE immunoglobulin to the solid phase was assumed to be less in CAP than in RAST. Pathogenic allergens diagnosed either clinically or by in vitro assay systems were compared. The sensitivity and specificity of the CAP system were 94.2% and 87.3%, respectively. CAP multi which binds groups of multiple allergens on the solid phase, was examined for the screening of hypersensitivity to categories of allergens. Statistical sensitivities of CAP multi resided between 63.9% to 86.2%, while the specificities were 98% to 100%, indicating that CAP multi is useful for the exploration of causative allergens. Phadiatop, which fixes multiple inhalant allergens, showed a sensitivity of 89.6%. The specificity of phadiatop was 93.9%, when examined for intrinsic bronchial asthma patients, and 91.2% for normal subjects indicating that phadiatop is more useful than total IgE measurement for the screening of atopic trait. PMID- 1883272 TI - [The morphofunctional characteristics of the blood lymphocytes in steroid sensitive and steroid-resistant glomerulonephritis]. AB - Morphofunctional properties of the lymphocyte suspension of patients susceptible and resistant to glucocorticoids in nephrotic form of glomerulonephritis were studied. Ultrastructural study of lymphocytes was performed as well as immune tests (the determination of lymphocyte glucocorticoid receptors number, proliferative activity of mononuclears, HIA genotypes) in 216 children. Morphofunctional insufficiency of the patient lymphocytes as compared to that in donors was established. A higher morphologic variety, functional sufficiency of lymphocytes, a higher number of glucocorticoid receptors and a preferable HIA genotype were found in the hormone-susceptible patients. Lymphocytes of hormone resistant patients were characterized by a high activity of RNA-synthesizing apparatus, the presence of damaged organelles, low number of glucocorticoid receptors and by the failure of proliferative response to the dexamethasone test. These differences allow the differential approach to glucocorticoid therapy. PMID- 1883271 TI - [An electron microscopic study of the effector link in immune reactions in stomach cancer]. AB - 21 surgically removed gastric carcinomas of different histologic structure and stage of development were studied ultrastructurally. A variety of morphological manifestations of local immune reactions and nonspecific antitumour resistance were observed. These manifestations were characterized by the contacts of lymphocytes, macrophages, polymorphonuclear leukocytes, plasma cells with each other and with tumour cells and by the presence of variable changes in tumour cells. The causes of such a variety are discussed and they may be due to different types of cytotoxicity, stage of the interaction between the effector and the target and so on. PMID- 1883273 TI - [The immunomorphological characteristics of the appendix in a viral-bacterial lesion in children with appendicitis]. AB - The characteristics of viral-bacterial lesion in the appendix of children with appendicitis are given by means of histologic, histochemical, immunomorphological and morphometric methods. Antigens of influenza viruses A, B, C, entero-, adeno- and paramyxoviruses were observed among which influenza C was found significantly more frequently (64.1%). Viral infection in the majority of cases (79.5%) was found in the association with opportunistic flora, more frequently with E. coli, and less R. aeruginosa and Klebsiella. Analysis of the immunomorphological shifts in the appendix indicated a peculiar dynamics of the antibody production in acute appendicitis: the enhancement of the IgG, IgD and IgE production and the decrease of the production of IgA and IgM. The viral-bacterial effect, the development of the immune responses with IgE hyperproduction and participation in this process of labrocytes and endocrine cells suggest the integration of the two pathogenetic mechanisms-infectious and allergic. PMID- 1883275 TI - [Patterns in the reorganization of the lymphatic bed of the heart in disordered lymph outflow]. AB - Current concepts of the structure and function of the heart lymphatic bed and role of the disturbance of lymph circulation in cardiac pathology are presented. The original clinical and experimental results obtained with the use of injection, stereoangioscopic and electron microscopic methods are summarized. General rules of the compensatory-adaptive and pathologic rearrangement of the damaged lymph drainage in the process of chronic lymphostasis development and the reversibility of these changes are described. The classification of the disturbances of the heart lymph circulation is considerably modified. PMID- 1883276 TI - [Changes in the 3-dimensional organization of the cellular system of the human aortic intima in atherosclerosis]. AB - Three-dimensional organization of the subendothelial aortal intima was studied by means of light microscopy of serial membranous preparations and scanning electron microscopy. Three-dimensional network composed of cells of varying shape is found in normal intima. Lipid inclusion in the lipid streak are found mainly in the stellate and roundish cells. Intercellular links are destroyed in the superficial layers of the lipid streak with extracellular lipid droplets being found in the region of the contact rupture. The cells are practically deprived of contacts in the marginal zone and central part of the atherosclerotic plaque cover where giant stellate cells integrated into the rough fibrillar connective tissue matrix are frequently found. PMID- 1883274 TI - [Opisthorchiasis cysts of the liver]. AB - Specimens from 7 livers resected because of opisthorchiasis cysts and 29 autopsy cases with massive opisthorchiasis invasion resulting in cholangiectasis and cyst formation in the liver were studied. Characteristic features of the liver opisthorchiasis cysts are described. PMID- 1883277 TI - [Angiodysgenetic necrotizing myelopathy (the Foix-Alajouanine syndrome)]. AB - One observation of a rare disease--angiodysgenetic necrotizing myelopathy--in a 50-year-old patient is described. The diagnosis was established at necropsy and did not confirm suspected spinal cord tumor and myelitis. The disease is angiodysplasia with resulting necrotizing myelopathy. Large dysplastic intra- and extramedullary vessels with a disturbed wall permeability, vascular malformations and necrotic foci in the spinal cord are characteristic for this condition. PMID- 1883278 TI - [Fahr's syndrome and infantile cerebral palsy--the sequelae of very severe hypoxia at birth in a child]. AB - A first-pregnancy child was delivered in the state of grave hypoxia. He was reanimated but later on Fahr's [correction of Fara's] syndrome developed. The symptoms of infantile cerebral paralysis appeared at the age of 5 months with tonic convulsions most likely as a consequence of Fahr's [correction of Fara's] syndrome. PMID- 1883279 TI - [Comments on the discussion on constructing a pathological anatomical diagnosis (apropos the article by D. S. Sarkisov)]. PMID- 1883280 TI - [The problems under discussion in establishing a diagnosis]. PMID- 1883281 TI - [Nosology and syndromology: searches for the etiology--striving for the exact diagnosis]. PMID- 1883283 TI - [Iatrogenic pathology and the possibilities for the practical pathological anatomist]. PMID- 1883282 TI - [Letter to the editor (apropos of the article by D. S. Sarkisov "On Diagnosis")]. PMID- 1883284 TI - [The discussion on diagnosis (apropos the article by D. S. Sarkisov Diagnosis)]. PMID- 1883285 TI - [A modification to the process of drying material in paraffin embedding in pathohistological practice]. AB - The modification consists of the replacement of alcohols of increasing concentration by glycerols. This results in a shortening of tissue treatment, improvement of the preparation quality due to the full exclusion of the alcoholic tissue shrinkage and cell structure deformation as well as alcohol saving. PMID- 1883286 TI - [The use of the microwave oven in the stages of preparing material for histological research]. PMID- 1883287 TI - [Georgii Stepanovich Kulesha (on the 60th anniversary of his death)]. PMID- 1883288 TI - [Breast fibroadenoma: the morphological characteristics, morphogenesis and prognosis]. AB - Morphology of mammary fibroadenoma (FA) is well studied while this is not the case for its morphogenesis and prognosis. The role of a stromal component in the development of FA is outlined. Immune response in FA is mainly directed to the fibroblasts. Further studies of mammary FA will allow one to reveal the biological properties of this tumour and to evaluate adequately its prognosis as in 0.5-2% of cases it undergoes malignant transformation. PMID- 1883289 TI - Proceedings of meetings of the Royal Australasian College of Physicians and special societies. Abstracts. PMID- 1883290 TI - Development and evaluation of a rapid absorbed enzyme immunoassay test for the diagnosis of Johne's disease in cattle. AB - An absorbed enzyme immunoassay (EIA) test for Johne's disease in cattle was developed in which absorption of cross-reacting antibodies occurred as a rapid reaction in solution rather than overnight with whole organisms and a subsequent centrifugation step. Total test time was reduced to less than 2 h with a minimum of manipulations. The test was evaluated in cattle herds from Johne's disease endemic and Johne's disease-free regions of Australia. Specificity was 99.8%. Calculations of sensitivity were affected by the history of the herd under test. However, the EIA detected in excess of 80% of animals before onset of clinical disease and 65% of faecal shedders were EIA positive on, or before, first detection of Mycobacterium paratuberculosis in their faeces. The test should aid epidemiological studies and be a useful tool in the management and control of Johne's disease. PMID- 1883291 TI - Eye diseases in Siberian husky dogs. AB - A full ophthalmic examination was performed on 40 Siberian husky dogs using direct and indirect ophthalmoscopy, gonloscopy and nasolacrimal cannulation. Eight (20%) of the dogs were found to have distichia, 10 (25%) had excessive medial caruncular hairs, 8 (20%) had absence, displacement, or narrowing of the nasolacrimal puncta, 2 (5%) had bilateral corneal crystalline opacities, and 2 (5%) had unilateral areas of lateral corneal lipidosis. Fifty percent of the dogs had some abnormality of the iridocorneal (drainage) angle. However, in only one of these was the deformity severe enough to require glaucoma prophylaxis. An association between blue iris colour and malformation of the iridocorneal angle was noted. PMID- 1883292 TI - Comparison of a liquid and a powder insecticidal dressing to aid healing and prevent flystrike of mulesing wounds in lambs. AB - A proprietary insecticidal mulesing powder containing diazinon and an experimental liquid dressing based on eucalyptus oil, naphthalene, cresylic acid and chlorfenvinphos in a carrier of liquid hydrocarbons and petroleum oil were compared for their ability to promote wound healing and reduce the incidence of fly strike in freshly mulesed lambs. Throughout the trial period of 4 weeks, fly trapping confirmed the presence of Lucilia cuprina in the paddock where the ewes and lambs were grazing At inspection one month after mulesing, no deaths had occurred since mulesing and no lambs showed evidence of cutaneous myiasis, although a number of their dams (with 8 months wool) were struck. At 4 weeks after mulesing, the wounds of the lambs treated with the experimental liquid dressing showed better healing than those treated with the powder dressing. It was concluded that both mulesing preparations were effective in inhibiting flystrike, but the liquid dressing promoted faster wound healing than did the powder. PMID- 1883293 TI - Evaluation of an immunofluorescence test on direct smears of conjunctival and urogenital swabs taken from koalas for the detection of Chlamydia psittaci. AB - The Chlamydia-Cel Vet IF Test (CCVIT), a commercially available immunofluorescence test for use on direct smears of clinical specimens, was evaluated in a colony of 43 captive koalas. The test is based on a monoclonal antibody directed against the chlamydial common group specific lipopolysaccharide antigen. Swabs were taken from conjuncitva and penis or urogenital sinus and used for direct smear evaluation and cell culture isolation. Compared with isolation of the organism in cell culture, the CCVIT on direct smears of conjunctival swabs presented a sensitivity of 88%, a specificity of 100%, a positive predictive value (PV+) of 100% and a negative predictive value (PV-) of 97%. The CCVIT on direct smears of urogenital swabs presented a sensitivity of 90%, a specificity of 84%, a PV+ of 86% and a PV- of 89%. The overall sensitivity was 89% (95% confidence interval [CI] of 71% to 97%), the specificity 94% (95% CI of 84% to 98%), the PV+ 89% and the PV- 94%. It was concluded that the CCVIT on direct smears was suitable as a diagnostic screening test for the detection of Chlamydia psittaci in koalas. PMID- 1883294 TI - Chlamydial infection in a colony of captive koalas. AB - Forty three koalas in a captive colony were investigated for the presence of Chlamydia psittaci infection and associated disease. Swabs were taken from conjunctivae and urogenital sites for cell culture isolation of C psittaci and for cytological examination (direct smears) for chlamydial inclusions and evidence of inflammation. On the basis of cell culture isolation, 28 samples from 25 koalas were positive for C psittaci (that is, infected). Three koalas were positive from both sites, 5 from conjunctivae alone and 17 from urogenital sites alone. Seven of the 8 koalas with positive conjunctival swabs had overt signs of conjunctivitis, but only 3 of the 20 koalas with positive urogenital swabs had overt signs of 'wet bottom' (continual urine soiling due to cystitis) or purulent discharge. However, 5 of the 20 with positive urogenital swabs had past episodes of 'wet bottom'. Moreover, examination of direct cytological smears showed evidence of inflammation (neutrophils) in 7 of 8 koalas with positive conjunctival swabs and 17 of 20 with positive urogenital swabs. Chlamydial inclusions were rarely identified with surety on direct cytological smears. In the 18 koalas without chlamydia, one had overt conjunctivitis while 2 had past episodes of conjunctivitis. The koala with conjunctivitis at the time of sampling had a prior history of 'wet bottom'. Examination of direct cytological smears revealed 2 of the chlamydial negative koalas had high numbers of neutrophils in urogenital smears. It was concluded that C psittaci infection may cause overt or sub-clinical disease, with the former developing when the koalas were stressed through management procedures or concomitant disease. PMID- 1883295 TI - A cross-sectional study to show Eperythrozoon ovis infection is prevalent in Western Australian sheep farms. AB - A serological survey and risk factor study was conducted to estimate the prevalence of Eperythrozoon ovis infection in Western Australian weaner sheep, the prevalence of farms with infected sheep, and to identify factors affecting initiation and maintenance of infection on the farm. The study was conducted on 91 farms, purposively chosen from 41 randomly selected regional shires stratified by sheep number and rainfall zones. Twenty sheep were selected systematically from a mixed-sex flock on each farm and tested for serum antibody to E ovis using an enzyme-linked immunosorbent assay. Information on putative risk factors was collected using an interview questionnaire. Antibody to E ovis was detected in 4.5% of sheep on 47% of the farms sampled. The prevalence of E ovis infection in sheep was estimated at the 95% confidence level to be between 3.6 and 5.5%, and the prevalence of farms with infected sheep was estimated to be between 37.5 and 56.5%. Most farms with serological evidence of infection occurred in the Great Southern agricultural region (79.5%), south-east of Perth through to Albany (latitude 32 to 34 degrees S, longitude 116 to 120 degrees E), and in the Northern region (12.8%) surrounding Geraldton (latitude 29 degrees S, longitude 114 degrees E). There were significantly more farms (P less than 0.05) with evidence of infection in the Great Southern region compared to the Central region between Geraldton and Perth, and on farms in the region south compared to north of latitude 32 degrees S. None of the putative risk factors examined in the questionnaire were associated with serological evidence of infection on the farm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883296 TI - Impact of dung from ivermectin-treated sheep on oogenesis and survival of adult Lucilia cuprina. AB - Females of the Australian sheep blowfly, Lucilia cuprina, exploit sheep dung as a source of protein for egg development. Flies fed on dung collected from sheep 1 to 6 days after being drenched with the broad-spectrum antiparasitic drug ivermectin showed delayed reproductive development and reduced fecundity. Male and female survival was also reduced. Despite these effects, except where the recommended frequency of drenching (1 to 4 times per annum) is greatly exceeded, it is unlikely that ivermectin residues will affect any useful reduction in blowfly populations. PMID- 1883297 TI - Bilateral hypoplasia of the soft palate in a foal. AB - Bilateral hypoplasia of the soft palate and aspiration pneumonia occurred in a Standardbred foal. The filly was presented with a history of illthrift, dyspnoea, coughing and bilateral nasal discharge. Abnormal sounds (crackels and wheezes) were auscultated over all lung fields and the cervical trachea. Endoscopy revealed a shortened soft palate with a uvula-like mass protruding from the free border into the nasopharynx. Mucopurulent material was present in the trachea. Samples obtained by tracheal wash were submitted for cytology, culture and sensitivity testing. Results indicated a septic inflammatory process. On lateral radiographs of the thorax there were patchy areas of consolidation and air bronchograms. The foal was euthanased. Necropsy confirmed the presence of a palatal defect and aspiration pneumonia of moderate severity. No other congenital abnormalities were present. PMID- 1883298 TI - Furazolidone toxicity in dairy calves. PMID- 1883299 TI - Injectable abamectin causes a delay in scarabaeine dung beetle egg-laying in cattle dung. PMID- 1883300 TI - Protection against ovine footrot using a topical preparation of zinc sulphate. PMID- 1883301 TI - The development of posttraumatic stress disorder following four different types of traumatization. AB - The Children's Posttraumatic Stress Disorder Inventory (CPTSDI) was used to identify 230 childhood posttraumatic stress disorder (PTSD) cases. Of these cases, 58 had been traumatized through direct experience, 128 through observation, 13 through verbal mediation, and 31 by combinations thereof. The 230 children and 35 controls completed the Revised Children's Manifest Anxiety Scale (RCMAS) and the Children's Depression Inventory (CDI). In addition, their conduct was rated on the Connor's Teacher Rating Scale (CTRS) criteria. Each of the PTSD groups had significantly greater RCMAS, CDI, and CTRS scores than the non clinical controls, but there were no differences between the four types of PTSD cases. PMID- 1883302 TI - Low sexual desire: sex therapy results and prognostic factors. AB - In a prospective study of 60 couples who entered sex therapy because of the female partners' low sexual desire, 38 (63.3%) completed treatment and 34 (56.7%) had a positive outcome. The principal predictor of completion of treatment was the male partners' apparent motivation at the outset. Poorer outcome was associated with younger age of the couple (especially the male partner) and a shorter duration of the sexual problem. Surprisingly, few aspects of the couples' general relationships prior to treatment were related to outcome, except for poorer outcome being associated with a history of previous separations. The apparent lack of significant contribution of general relationship factors and psychopathology to outcome probably reflects the stringency of the initial selection process. Eventual outcome was also related to couples' progress by the third treatment session. The modest outcome of treatment for low sexual desire in this and other studies emphasises the need for further understanding of factors which contribute to this problem and for the development of novel treatment strategies. PMID- 1883303 TI - Similarities and differences on five inventories among mood and anxiety disorder patients. AB - The Eysenck Personality Questionnaire (EPQ), BAROMAS, Leisure Interests Checklist (LIC), Mental Health Inventory (MHI) and a one-page checklist of Body Problems were given to 128 outpatients with serious mood or anxiety disorders. Compared to normative data published on the first four devices, the combined patients were far 'sicker' in nearly all comparisons (P less than or equal to 0.01). However, anxiety and mood patients did not differ on the EPQ, BAROMAS, or LIC. On Body Problems, strong contrasts emerged (P less than 0.04), especially when 'fringe' cases were excluded (e.g. dysthymics from mood, and obsessives from anxiety disorder diagnoses). Small anxiety subtype groups also differed (P less than 0.05). On the MHI, both global and core groups of mood--especially unipolar (depressed)--patients differed from the anxiety disorders (P less than 0.04). PMID- 1883304 TI - Assessing emotional distress at the internist's office. AB - At their first visits to a clinic, 102 outpatients rated the severity of their presenting complaint, of 12 possible body problems including 6 nonspecific symptoms, of a set of adjustment difficulties, and answered the Welsh A and the Beck Depression inventories. Then, an internist 'blind' to the foregoing answers performed a routine history and physical exam, afterward rating the patient for degree of organic and of psychosomatic involvement. Significant correlations were found between clinician judgments of psychosomatic involvement and patients' self reported complaints on all assessment measures (smallest r = 0.25, P less than 0.01). Substantial intercorrelations were found among the assessment measures, especially between Welsh A (Anxiety) and Beck Depression scores (r = 0.73). PMID- 1883305 TI - An experimental investigation of thought suppression. AB - An experiment investigating the hypothesis that trying to suppress a thought will lead to an immediate and/or delayed increase in its occurrence is reported. Normal subjects listened to a taped story and then verbalized their stream of consciousness during two consecutive time periods. During the first period, one group (suppression) were asked not to think about the tape while two other groups (controls) were asked to think about anything or think about anything including the tape. During the second period, all three groups were instructed to think about anything. Results from the first period failed to support the immediate enhancement hypothesis as the suppression group reported less thoughts about the tape than the controls. However, results from the second period supported the delayed (rebound) hypothesis as subjects who had previously suppressed reported more thoughts about the tape than subjects who had not. The theoretical, methodological, and clinical implications of these results are discussed. PMID- 1883306 TI - The relationship among guilt, dysphoria, anxiety and obsessions in a normal population--an attempted replication. AB - The results of a previous study indicated that guilt as rated on the Perceived Guilt Index (PGI), predicted unpleasant intrusive thoughts, but self-reported anxiety and depression did not. In the present investigation, subjects indicated whether or not they experienced both pleasant and unpleasant intrusive thoughts, their frequency and a rating of how pleasant or unpleasant these thoughts were. They also completed self report ratings of depression, anxiety, obsessional ritualizing, and the PGI. Results of a regression analysis indicate that the best standardised questionnaire predictor of unpleasant intrusive thoughts is depression as rated on the BDI, and anxiety as rated on the BAI. The best standardised questionnaire predictor of pleasant intrusive thoughts is low anxiety. The PGI does not independently predict pleasant or unpleasant intrusive thoughts. PMID- 1883307 TI - Male sexual fantasy: multidimensionality in content. AB - Sixty-six men provided ratings of the extent to which they regarded fantasies depicting nominated sexual activities as sexually arousing. A Male Sexual Fantasy Questionnaire (MSFQ) with five subscales was constructed following factor analysis of these ratings. The subscales yield separate scores for fantasies representing sensual, genital, public sex, sexual dominance-submission, and sexual aggression themes. Levels of penile tumescence recorded while men engaged in fantasies depicting content represented in the MSFQ correlated with the extent to which these men earlier had rated these same fantasies as sexually arousing. Since ratings on the MSFQ did not correlate substantially or consistently with scores on the Betts Questionnaire Upon Mental Imagery, the Imaginal Processes Inventory, and the Gordon Test of Visual Imagery Control, sexual fantasy may be mediated by processes different from those involved in non-sexual imagery and daydreaming. The need to validate use of the MSFQ in several clinical contexts is noted. PMID- 1883308 TI - Relationship of intelligence with cognitive therapy outcome. AB - Theorists have speculated that intelligence is positively associated with the capacity to benefit from cognitive-behavioral therapies. We evaluated this notion by relating pre-treatment measures of fluid and crystallized intelligence to self reported symptom reduction in a naturalistic study (n = 106) of cognitive therapy for outpatients with principal diagnoses of major depression, dysthymia, or generalized anxiety disorder. Intelligence measures did not significantly predict outcome, and nonsignificant relationships were in the opposite direction from the theoretical prediction. Discussion centered on possible limitations to the generalizability of these results and on the logical interpretation of prediction studies in psychotherapy research. PMID- 1883310 TI - The efficacy of breathing retraining and the centrality of hyperventilation in panic disorder: a reinterpretation of experimental findings. AB - The present paper addresses de Ruiter, Rijken, Garssen, and Kraaimaat's (Behaviour Research and Therapy, 27, 647-655, 1989) interpretation of data pertaining to the efficacy of breathing retraining in the treatment of panic disorder. The proffered reinterpretation of these data makes it clear that breathing retraining led to a significant reduction in the frequency of panic attacks. These findings thus lend additional support to the central role of hyperventilation in primary panic attacks. PMID- 1883309 TI - The triple response approach to assessment: a conceptual and methodological reappraisal. AB - Despite its positive effects on the increased use of multiple assessments and improved assessment validity, the triple-response concept has led to some conceptual and practical confusion. This is mainly due to two problems: (1) a confounding of the content and method of assessment; and (2) an imprecise and vague use of the 'verbal-subjective mode' which has been expanded to include cognitive elements since the introduction of cognitive-behavioural theories and treatments. A new matrix is proposed that clearly distinguishes content and method of assessment. It also defines a separate cognitive/information-processing content area and introduces affect as an additional content area. Thus, four content areas are suggested: behavioural, physiological, cognitive, and affective, which can be measured in three different ways: by means of self report, observation, and instruments or technical equipment. We point out the implications of these changes for (1) a more appropriate selection of assessment procedures and outcome measures in clinical research; (2) a more adequate individualization of treatment through matching individual response profiles to specific treatments; and (3) an improved understanding of the interrelationship between behavioural, physiological, cognitive, and affective processes in anxiety and depression. Finally, we suggest that the lack of agreement between measures of physiological, cognitive, behavioural and affective changes in some studies may be as much a reflection of the lack of agreement arising from spurious sources of variance within content areas as it is a reflection of the operation of different processes and systems. PMID- 1883311 TI - [The problems of X-ray image formation in veterinary practice--result of a cyclic study with the use of a test phantom for the determination of image quality]. AB - To grasp the problems of producing X-ray pictures in veterinary surgery, a ring trial was carried out. The task of the veterinarians was to produce two radiographs: from a certain body region, together with a test phantom, which allowed the judgement of the image quality immediately. The dates and technique of exposure had to be chosen as usual, one picture had to be developed in the dark room, either manually--the usual way with the normally used chemicals or by automatic developing machine. The other picture was developed under standard conditions in the Institute of Medical Physics. For a third radiograph, already exposed with the correct dose, only development was requested. Therewith the total process of producing an x-ray picture, the exposure dates and -technique and the dark-room procedure should be analyzed. Additionally a protocol was drawn up. All results were treated anonymously. The outcome of the trial obviously showed the problems: blatant tendency to overexposure, in no case underexposure, combined with faults in the dark room--e.g. disregarding the condition of the developer or the probably given necessity of changing the developer and even the importance of controlling time and temperature during developing. No informations were requested about fixation- and stop bath or the method of drying.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883312 TI - [An experimental contribution to the epizootiology of viral hemorrhagic septicemia of rabbits (rabbit hemorrhagic disease, RHD)--transmission by flies]. AB - In experiments adapted to natural conditions it was established that--a conjunctival infection with about 100 RHD-virus particles was successful--in a milieu without flies transmission over a distance of only 50 cm did not take place--iridescent flies (Phormia spp.) seven hours after contamination with RHD virus material from died rabbits transmitted RHD to susceptible rabbits in an isolated cage. It ist supposed that transmission in this way will be an epizootiological important one for spreading in narrow distances. PMID- 1883313 TI - [The content of minerals and Fe, Cu and Zn in blood plasma, in erythrocytes and in 10 different tissues of bulls, short scrotum bulls and oxen]. AB - The concentrations of minerals (Ca, Mg, Na, K, total-P) and of trace elements (Fe, Cu, Zn) in the plasma and erythrocytes of bulls, of experimentally induced cryptorchids (Muchsen) and of oxen of the breed Holstein-Friesian and of bulls and cryptorchids of a hybrid breed with a high portion of meat-cattle were investigated. Further the concentrations in various tissues (M. semimembranosus, M. longissimus dorsi, left and right ventricle, liver, kidney, adrenal glands, lung, spleen, testis) in bulls, cryptorchids and oxen of the breed Holstein Friesian were analyzed. The differences of some concentrations of various elements in some tissues are discussed relative to their genesis and significance. PMID- 1883314 TI - [Cardiology for the veterinary practice--information processing with the help of a computer program, with a working example]. AB - Description of a PC-Program "Cardiology for the Veterinary Practice", title "Kardiag", with Illustrations and a report of a congenital heart disease in a one year old, male, Newfoundland dog, with the use of the described PC-Program. After euthanasia an autopsy was performed which verified the clinical diagnosis. PMID- 1883316 TI - Protein analysis during the ontogeny of normal and male sterile stamenless-2 mutant stamens of tomato (Lycopersicon esculentum Mill.). AB - The levels and synthesis of proteins during the ontogeny of normal and male sterile stamenless-2 (sl-2/sl-2) mutant stamens of tomato (Lycopersicon esculentum) were examined. The mutant stamens contained low levels of soluble protein which were related to reduction in protein synthesis. The mutant stamens, however, possessed many polypeptides similar to the normal and synthesized a 53 kd polypeptide at stages when there are abnormalities in tapetum development. The mutant stamens also possessed a 23-kd and some low molecular weight polypeptides that were considered as degradative proteins. Normal stamens exhibited the synthesis of many polypeptides not found in the mutant, from microspore mother cell to the preanthesis stages. In addition, at the time of pollen maturation there was a greater synthesis of several polypeptides, particularly those of 42 and 37 kd. Although the causative mechanisms of male sterility in the sl-2/sl-2 mutant are not known, the synthesis, and the lack, of specific polypeptides reported here appears to be associated with pollen degeneration. PMID- 1883317 TI - Genetic control of elsholtziaketone formation in Perilla frutescens. PMID- 1883318 TI - Genetic polymorphism of sorbitol dehydrogenase in the brown hare and the distribution of the variation in central Europe. AB - A genetic polymorphism of sorbitol dehydrogenase (SDH; EC 1.1.1.14) for two allozymes is demonstrated in the brown hare (Lepus europaeus) by means of horizontal starch gel electrophoresis. Segregation analysis was performed in a sample of four matings with 12 offspring and confirmed the genetic hypothesis: two alleles at an autosomal locus. The calculated gene frequencies in the brown hare breed studied are Sdha = 0.712 and Sdhb = 0.288. The distribution of the polymorphism in free-ranging brown hare populations from Austria, Czechoslovakia, Hungary, and Poland is described. PMID- 1883315 TI - Regulation of nuclear histone acetyltransferase by nucleic acids, histone.DNA complex, and chromatin. AB - Nuclear histone acetyltransferase is found to be inhibited by various nucleic acids and components. Of the adenosine phosphates, the order of inhibitory potency is ATP greater than ADP greater than AMP. Among the nucleoside triphosphates, GTP seems to be the best inhibitor, followed by ATP, CTP, and UTP. Deoxymononucleotides have the same order of inhibition potential as their ribonucleotide counterparts, with inhibition constants in the low millimolar range. Oligonucleotides and polynucleotides are much better inhibitors than mononucleotides. The inhibition constants of the DNA molecules are size dependent. Molecules larger than 40 base pairs have inhibition constants less than 18 micrograms/ml, whereas molecules with decreasing numbers of base pairs have increasing magnitudes of inhibition constants. However, acetyltransferase has a lower affinity for free DNA molecules than for DNA.histone complexes as revealed by its interaction with DNA-Sepharose and histone.DNA-Sepharose columns. Furthermore, native chromatin depleted of endogenous histone acetyltransferase activity shows no inhibitory effect on the enzyme. Yet heated chromatin not only loses substrate activity but also becomes an inhibitor for the enzyme. Since unmodified sea urchin sperm chromatin has been shown to be a potent acetyltransferase inhibitor, it seems possible that DNA.histone complexes may be the true inhibitory species and that the conformational states of such complexes may serve as a regulatory mechanism in the control of the enzyme activity. PMID- 1883319 TI - Genetic characterization of esterase 28 (ES-28) of the house mouse. AB - The genetics of esterase-28, the major esterase of cauda epididymidis of the house mouse, has been studied after separation by polyacrylamide gel electrophoresis and isoelectric focusing. Four phenotypes are distinguished. Segregation of Es-28 in two backcross series indicated linkage to Es-1, Es-9, and Es-22. The Es-28 locus was placed into esterase cluster 1 on chromosome 8. PMID- 1883320 TI - A quantitative genetic analysis of tissue-specific catalase activity in Mus musculus. AB - Tissue-specific catalase activity in 3-week-old animals from inbred mouse strains 129/ReJ, BALB/c, C3H/HeAnl/Cas-1b, C3H/HeSnJ, C3H/S, C57BL/6J, and Swiss-Webster was found to be highly variable by analysis of variance (P = 0.01). Appropriate crosses were made among strains which were classified as normal (BALB/c, C3H/HeSnJ, C3H/S), hypocatalasemic (129/ReJ, C57BL/6J), and acatalasemic (C3H/HeAnl/Cas-1b) with respect to blood catalase activity to study the inheritance of the blood, kidney, liver, and lung catalase activity levels in a number of generations (reciprocal F1's, F2, two backcrosses--BC1 and BC2--and some RI lines). Segregation analysis and statistical methods which tested different models of inheritance as well as calculations of heritability were used in an effort to assess and evaluate genetic parameters that affect catalase activity. Results indicate that the inheritance of blood catalase activity in the cross involving acatalasemic and normal (BALB/c, C3H/HeSnJ) strains is compatible with the single-locus difference between the parental strains; however, the difference between the acatalasemic and the hypocatalasemic strain (C57BL/6J) would require additional genetic interaction for a satisfactory explanation. A similar pattern of generalization also applies to the inheritance of kidney catalase activity. The segregation pattern for the liver and lung catalase activity in most crosses is significantly different from the expectations of the single locus model. These results are compatible with the concept that a number of genes must affect tissue-specific catalase activity in mice. These may include previously described (e.g., Ce-1 and Ce-2) or novel genetic regulators/modifiers which interact with a single structural gene (Cas-1) or its product to produce the catalase phenotype characteristic of specific tissues in each strain. PMID- 1883322 TI - Substrate-specificity of glutamine transporters in membrane vesicles from rat liver and skeletal muscle investigated using amino acid analogues. AB - We investigated the effects of glutamine and histidine analogues on glutamine transport processes in membrane vesicles prepared from rat liver (sinusoidal membrane) and skeletal muscle (sarcolemma). L-[14C]Glutamine is transported in these membranes predominantly by Systems N/Nm (liver and muscle respectively), and to a lesser extent by Systems A and L (e.g. about 60, 20 and 20% of total flux respectively via Systems N, A and L at 0.05 mM-glutamine in liver membrane vesicles). The glutamine anti-metabolites 6-diazo-5-oxo-L-norleucine and acivicin were relatively poor inhibitors of glutamine uptake into liver membrane vesicles (less than 25% inhibition at 20-fold excess) and appeared primarily to inhibit System A activity (i.e. N-methylaminoisobutyric acid-inhibitable glutamine uptake). In similar experiments azaserine (also a glutamine anti-metabolite) inhibited approx. 50% of glutamine uptake, apparently by inhibition of System A and also of System L (i.e. 2-amino-2-carboxybicyclo[2,2,1]heptane-inhibitable glutamine uptake). Glutamate gamma-hydroxamate, aspartate beta-hydroxamate, histidine and N'-methylhistidine were all strong inhibitors of glutamine uptake into liver membrane vesicles (greater than 65% inhibition at 20-fold excess), but neither homoglutamine nor N'-methylhistidine produced inhibition. L-Glutamate gamma-hydroxamate was shown to be a competitive inhibitor of glutamine transport via System N (Ki approximately 0.6 mM). Glutamine uptake in sarcolemmal vesicles showed a similar general pattern of inhibition as in liver membrane vesicles. The results highlight limits on the substrate tolerance of System N; we suggest that the presence of both an L-alpha-amino acid group and a nitrogen group with a delocalized lone-pair of electrons (amide or pyrrole type), separated by a specific intramolecular distance (C2-C4 chain equivalent), is important for substrate recognition by this transporter. PMID- 1883323 TI - The expression of glycogen phosphorylase in normal and dystrophic muscle. AB - Specific cofactor labelling was employed to determine the degradation rate of glycogen phosphorylase in normal adult C57BL/6J mice and their dystrophic counterparts (C57BL/6Jdy/dy). The rate constant for the decay of phosphorylase bound label was 0.125 day-1 in normal muscle and 0.49 day-1 in dystrophic muscle, i.e. a lower rate of catabolism of phosphorylase in dystrophic muscle. Quantitative Northern-blot analyses of total RNA isolated from normal and dystrophic muscle indicated that the abundance of phosphorylase mRNA as a percentage of total RNA was approx. 40% lower in dystrophic muscle. The specific activity of phosphorylase in dystrophic muscle is approx. 60% lower than in normal muscle, and is elicited by a lower rate of turnover of the enzyme, i.e. both synthesis and degradation are decreased. PMID- 1883321 TI - Structural aspects of protein-DNA recognition. PMID- 1883324 TI - Dexamethasone inhibits the hexose monophosphate shunt in activated rat peritoneal macrophages by reducing hexokinase-dependent sugar uptake. AB - Dexamethasone decreases 2-D-deoxyglucose (2-dGlc) uptake and accumulation into rat peritoneal macrophages in vitro in a concentration- and time-dependent manner (Ki for 1 microM-dexamethasone after a 2 h exposure = 0.71 +/- 0.21 microM; Ki for 0.1 microM-dexamethasone after exposure for 4 h = 0.10 +/- 0.06 microM). The inhibition of 2-dGlc uptake is consistent with a decrease in the coupling between endofacial hexokinase activity and the sugar transporter. The evidence for this is: (1) the Km for zero-trans 2-dGlc uptake in quiescent macrophages was increased by dexamethasone, but there was no significant effect on the Vmax.; (2) dexamethasone increased the rate of exit of sugar from cells preloaded with 2 dGlc; (3). the free sugar accumulation within the cytosol of the cells above the external solution concentration was significantly decreased by dexamethasone. These effects of dexamethasone on 2-dGlc transport were antagonized by simultaneous exposure to the steroid RU 38486 (Ki = 0.04 +/- 0.01 microM; 4 h incubation). Although dexamethasone inhibited zero-trans uptake, the maximum rate of infinite-trans exchange uptake of 2-dGlc into cells preloaded with 3-O-methyl D-glucose (40 mM) was unaltered by dexamethasone or RU 38486, indicating that the dexamethasone-dependent decrease in zero-trans uptake was not due to a change in the number of transporters in the plasma membrane. Dexamethasone also inhibited the phorbol myristate acetate-induced stimulation of hexose monophosphate shunt (HMPS) activity, and this was reversed by RU 38486. Cytochalasin B, the potent sugar-transport inhibitor, inhibited HMPS activity and 2-d[2,6-3H]Glc uptake equally, indicating a single site of action. By contrast, dexamethasone showed differential inhibition of HMPS activity and 2-d[2,6-3H]Glc uptake, suggesting that it not only acts by decreasing the coupling between hexokinase and sugar transport, but also at one or more additional points. PMID- 1883325 TI - A novel glutathione transferase (13-13) isolated from the matrix of rat liver mitochondria having structural similarity to class theta enzymes. AB - A rat liver mitochondrial-matrix fraction was prepared and shown to have 1-chloro 2,4-dinitrobenzene(CDNB)-metabolizing glutathione transferase (GST) activity. Further fractionation by sequential gel filtration, isoelectric focusing or chromatofocusing and hydroxyapatite chromatography yielded three GSTs of pI 9.3, 8.9 and 7.5, none of which bound to a GSH-agarose affinity matrix. Most of the activity was associated with the pI-9.3 form, which was selected for further study. Its activity was tested with the following potential substrates in addition to CDNB: 1,2-dichloro-4-nitrobenzene, p-nitrobenzyl chloride, trans-4 phenylbut-3-en-2-one, 1,2-epoxy-3-(p-nitrophenoxy)propane, ethacrynic acid, menaphthyl sulphate, cumene hydroperoxide, linoleic acid hydroperoxide and 4 hydroxynon-2-enal. Appreciable activity was obtained only with CDNB and ethacrynic acid (82 and 26 mumol/min per mg of protein respectively). The apparent Km for GSH, using 1 mM-CDNB, was 1.9 mM. The enzyme is a dimer of subunit Mr 26,500. It has a free N-terminus, which has enabled the first 33 amino acids to be sequenced. This portion of primary structure has a sequence in common with members of the Theta class of GSTs (eg. 36% identity with subunit 12) and also a sequence which might function as a mitochondrial import signal. It is novel and has been named 'GST 13-13'. PMID- 1883326 TI - Link protein as a monitor in situ of endogenous proteolysis in adult human articular cartilage. AB - The link protein components of proteoglycan aggregates in adult human articular cartilage show heterogeneity due to proteolysis. Cleavages near the N-terminus of the intact link proteins, before residues 17, 19 and 24, generate three proteins of slightly diminished size (LP3). Cleavages within the N-terminal disulphide bonded loop, before residues 66 and 73 of the intact link proteins, generate proteins that yield smaller degradation products upon reduction (LP fragments). In vitro, modified link protein components of a similar size to LP3 can be generated by a variety of proteinases, but of the physiologically relevant enzymes only stromelysin, cathepsin B and cathepsin G have the ability to yield modified link proteins with N-termini identical with those observed in situ. None of the proteolytic agents tested was able to produce LP fragments with N-termini identical with those observed in situ, and the majority of proteinases were not able to cleave within the disulphide-bonded loops. Cathepsin L and hydroxyl radicals can cleave within the N-terminal disulphide-bonded loop, and have the potential of initially opening the loop to allow further proteolytic processing by other agents to generate the native cleavage sites. PMID- 1883327 TI - 5-Lipoxygenase is not essential in macrophage-mediated oxidation of low-density lipoprotein. AB - The concentration-dependent effects of a series of lipoxygenase inhibitors and antioxidants on the macrophage-mediated oxidative modification of low-density lipoprotein (LDL) were measured. Their influence on macrophage 5-lipoxygenase pathway activity was also studied over the same concentration range. No correlation between inhibition of 5-lipoxygenase and of macrophage-mediated oxidation of LDL was observed. The capacity of the compounds to prevent cell mediated modification of LDL could be explained in terms of their activity as either aqueous- or lipid-peroxyl radical scavengers. Two potent 5-lipoxygenase inhibitors (MK 886 and Revlon 5901), which had no radical-scavenging properties, were unable to block LDL modification. It is concluded that 5-lipoxygenase is not essential for LDL oxidation by macrophages. PMID- 1883329 TI - Inhibition by inorganic anions of glutathione S-transferases from insect and mammalian sources. AB - Glutathione S-transferases 1-1, 3-3, 3-4 and 4-4 from rat liver and the major glutathione S-transferase from the wax moth (Galleria mellonella) are all inhibited by several simple inorganic anions. For each of 3-3, 3-4 and the insect enzyme, the order of inhibitory potency was ClO4- greater than or equal to SCN- greater than I- greater than NO3- greater than Br-. A more limited range of anions was tested on the isoenzymes 1-1 and 4-4, but the same trend was apparent. Values for Ki ranged from about 200 mM for Cl- to 6 mM for SCN- in the case of the insect enzyme and from 50 mM for Br- to 0.3 mM for SCN- for the rat isoform 3 3. Acetate, F-, SO4(2-) and PO4(3-) were not found to have significant inhibitory properties. The mode of inhibition was characterized as non-competitive in the case of the insect enzyme and rat transferase 1-1, whereas the mode of inhibition was partially non-competitive in the case of the rat isoforms 3-3, 3-4 and 4-4. PMID- 1883328 TI - Properties of subunits of the multicatalytic proteinase complex revealed by the use of subunit-specific antibodies. AB - The multicatalytic proteinase (MCP) is a high-molecular-mass non-lysosomal proteinase that gives rise to a characteristic pattern of bands of molecular mass 22-34 kDa on SDS/PAGE gels. Isoelectric-focusing gels of the enzyme purified from rat liver show 16 bands with isoelectric points in the range of pH 5-8.5. Two dimensional PAGE gels reveal that there are more than the previously reported 13 polypeptides associated with the MCP from rat liver and show a pattern of 15-20 major spots and several minor ones, similar to that of MCP isolated from some other sources. Possible relationships between the different polypeptides were investigated by immunoblot analysis of electrophoretically purified proteinase subunits with affinity-purified subunit-specific antibodies as well as antibodies raised against individual denatured subunits of the complex. The results demonstrate that many of the major polypeptide components of the MCP complex are antigenically distinct. Moreover comparison of immunoreactive material in crude cell extracts with that in purified MCP preparations has shown that the polypeptides are not derived from a smaller number of higher-molecular-mass subunits. Also, individual subunits have the same apparent molecular mass in a variety of rat tissues, suggesting close similarity between MCPs of different tissues. The highest concentrations of MCP subunits occur in liver and kidney. Gel-filtration analysis of crude extracts has demonstrated that MCP polypeptides are also associated with a higher-molecular-mass complex, which may be the 26 S proteinase that has been implicated in the degradation of ubiquitin-protein conjugates. PMID- 1883330 TI - Expression of a cDNA clone encoding the haem-binding domain of Chlorella nitrate reductase. AB - A partial cDNA clone coding for the haem-binding domain of NADH:nitrate reductase (EC 1.6.6.1) (NR) from the unicellular green alga Chlorella vulgaris has been isolated, sequenced and expressed. A 1.2 kb cDNA (pCVNR1) was isolated from a lambda gt11 expression library produced from polyadenylated RNA extracted from nitrate-grown Chlorella cells. pCVNR1 hybridized to a 3.5 kb mRNA transcript that was nitrate-inducible and absent from ammonium-grown cells. The entire sequence of pCVNR1 was obtained and found to have a single uninterrupted reading frame. The derived amino acid sequence of 318 amino acids has a 45-50% similarity to higher-plant NRs, including Arabidopsis thaliana, spinach (Spinacia oleracea) and tobacco (Nicotiana tabacum). A comparison with the putative domain structure of higher-plant nitrate reductases suggested that this sequence contains the complete haem-binding domain, approximately one-third of the Mo-pterin domain and no FAD-binding domain. A 32% sequence similarity is evident when comparing the Chlorella NR haem domain with that of calf cytochrome b5. Expression of pCVNR1 in a pET vector synthesized a 35 kDa protein that was antigenic to anti-(Chlorella NR) antibody. The spectral properties of this protein (reduced and oxidized) in the 400-600 nm region are identical with those of native Chlorella NR and indicate that haem is associated with the protein. PMID- 1883331 TI - Citrate synthase from Mycobacterium smegmatis. Cloning, sequence determination and expression in Escherichia coli. AB - A Mycobacterium smegmatis PstI library was constructed by cloning these fragments downstream from the lac promoter of the expression vector pHG171. Three identically sized clones were isolated by complementation of an Escherichia coli strain (chi 2338) deficient in citrate synthase. One insert (pBL265) was used in hybridization experiments with DNA from E. coli and M. smegmatis and it was demonstrated that the clones were indeed from M. smegmatis. The transcription of the M. smegmatis citrate synthase gene in E. coli relied upon the lac promoter. In translation experiments performed in vitro pBL265 gave rise to a novel protein of about 42 kDa. This band was not seen in 'opposite-orientation' subclones. Various subclones in which the 5'-end was shortened nevertheless complement E. coli chi 2338 and produce the 42 kDa protein. This demonstrates that the M. smegmatis citrate synthase gene uses its own ribosome-binding site in E. coli. The relevant 1.8 kb of the 2.8 kb insert was sequenced. A consensus E. coli ribosome-binding site was found centred precisely 10 bp upstream of the methionine codon. Other interesting features revealed by the sequence are discussed. Citrate synthase activity was assayed in vitro and the mycobacterial enzyme was found to be similar to those of the Gram-positive bacteria. PMID- 1883332 TI - Determination of the rates of appearance and loss of glucose transporters at the cell surface of rat adipose cells. AB - We have used an impermeant bis-mannose compound (2-N-[4-(1-azi-2,2,2 trifluoroethyl)benzoyl]-1,3-bis-(D-mannos+ ++- 4-yloxy)-2- propylamine; ATB-BMPA) to photolabel the glucose transporter isoforms GLUT4 and GLUT1 that are present in rat adipose cells. Plasma-membrane fractions and light-microsome membrane fractions were both labelled by ATB-BMPA. The labelling of GLUT4 in the plasma membrane fraction from insulin-treated cells was approximately 3-fold higher than that of basal cells and corresponded with a decrease in the labelling of the light-microsome fraction. In contrast with this, the cell-surface labelling of GLUT4 from insulin-treated intact adipose cells was increased approximately 15 fold above basal levels. In these adipose cell preparations, insulin stimulated glucose transport activity approximately 30-fold. Thus the cell-surface labelling, but not the labelling of membrane fractions, closely corresponded with the stimulation of transport. The remaining discrepancy may be due to an approx. 2-fold activation of GLUT4 intrinsic transport activity. We have studied the kinetics of trafficking of transporters and found the following. (1) Lowering the temperature to 18 degrees C increased basal glucose transport and levels of cell surface glucose transporters by approximately 3-fold. This net increase in transporters probably occurs because the process of recruitment of transporters is less temperature-sensitive than the process involved in internalization of cell-surface transporters. (2) The time course for insulin stimulation of glucose transport activity occurred with a slight lag period of 47 s and a t 1/2 3.2 min. The time course of GLUT4 and GLUT1 appearance at the cell surface showed no lag and a t 1/2 of approximately 2.3 min for both isoforms. Thus at early times after insulin stimulation there was a discrepancy between transporter abundance and transport activity. The lag period in the stimulation of transport activity may represent the time required for the approximately 2-fold stimulation of transporter intrinsic activity. (3) The decrease in transport activity after insulin removal occurred with a very high activation energy of 159 kJ.mol-1. There was thus no significant decrease in transport or less of cell-surface transporters over 60 min at 18 degrees C. The decrease in transport activity occurred with a t1/2 of 9-11 min at 37 degrees C.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1883333 TI - Role of spermine in mammalian sperm capacitation and acrosome reaction. AB - The binding properties of seminal polyamines to ram spermatozoa and their possible role in sperm capacitation and the acrosome reaction were studied. Binding and release of [14C]spermine from ram spermatozoa occurred at a rate faster than in somatic cells and were not energy-dependent. Release of bound spermine was further facilitated by heparin, a constituent of the female reproductive tract which was reported to induce capacitation and the acrosome reaction. High- and low-affinity polyamine-binding sites were identified, of which the high-affinity site was specific to polyamines with three or more amino groups. We also found that spermine inhibited the acrosome reaction and propose that it is the major seminal decapacitating factor. Since precise timing of capacitation and the acrosome reaction are critical for successful fertilization, it is suggested that the role of seminal spermine is to prevent premature capacitation and the acrosome reaction. PMID- 1883335 TI - Phospholipase A2 in human ascitic fluid. Purification, characterization and immunochemical detection. AB - A phospholipase A2 (PLA2, EC 3.1.1.4) was purified from human cell-free ascitic fluid (a-PLA2) by ion-exchange chromatography and h.p.l.c. on a reverse-phase column to apparent homogeneity. The enzyme had an Mr of approx. 10,000 as determined by SDS/PAGE. Polyclonal antibodies raised in a rabbit were specific to a-PLA2, as judged by immunoblotting. A time-resolved fluoroimmunoassay (TR-FIA) for measuring the concentration of a-PLA2 in various body fluids was developed. The detection limit of the assay was about 6 ng/ml. The antiserum did not cross react with pancreatic secretory phospholipase A2 as measured by TR-FIA. The enzyme content was studied in various samples, including normal human serum, buffy-coat leucocytes, synovial fluid, and pancreas and spleen homogenates. PMID- 1883334 TI - The relationship between cytosolic Ca2+, sn-1,2-diacylglycerol and inositol 1,4,5 trisphosphate elevation in platelet-activating-factor-stimulated rabbit platelets. Influence of protein kinase C on production of signal molecules. AB - The temporal and dose-response relationships of platelet-activating-factor (PAF) induced changes in the concentrations of cytosolic Ca2+ ([Ca2+]i), Ins(1,4,5)P3 and 1,2-diacylglycerol (DAG) were examined. In addition, phosphorylation of protein kinase C (PKC) substrate (40-47 kDa protein) was determined. In high-dose PAF-activated platelets, all three signal molecules increased rapidly and transiently, with the peak Ins(1,4,5)P3 concentration preceding maximal elevation of [Ca2+]i by 5 s. In low-dose PAF-activated platelets there were large increases in [Ca2+]i and dense-granule release, without any increase in Ins(1,4,5)P3 and DAG or 40-47 kDa protein phosphorylation. Staurosporine, a non-specific PKC inhibitor, produced enhanced elevations in the concentrations of Ins(1,4,5)P3, DAG and thromboxane B2, and the duration of the Ca2+ signal in platelets stimulated with a high dose, but not a low dose, of PAF. These results suggest there are both phospholipase C-dependent and -independent changes in Ca2+ homoeostasis. Endogenously activated PKC regulates the formation of signal molecules. PMID- 1883336 TI - The mouse androgen receptor. Functional analysis of the protein and characterization of the gene. AB - Screening a mouse genomic DNA library with human androgen-receptor (hAR) cDNA probes resulted in the isolation and characterization of eight genomic fragments that contain the eight exons of the mouse androgen-receptor (mAR) gene. On the basis of similarity to the hAR gene, the nucleotide sequences of the protein coding parts of the exons as well as the sequences of the intron/exon boundaries were determined. An open reading frame (ORF) of 2697 nucleotides, which can encode an 899-amino-acid protein, could be predicted. The structure of the mAR ORF was confirmed by sequence analysis of mAR cDNA fragments, which were obtained by PCR amplification of mouse testis cDNA, using mAR specific primers. A eukaryotic mAR expression vector was constructed and mAR was transiently expressed in COS-1 cells. The expressed protein was shown by Western blotting to be identical in size with the native mAR. Co-transfection of HeLa cells with the mAR expression plasmid and an androgen-responsive chloramphenicol acetyltransferase (CAT) reporter-gene construct showed mAR to be able to trans activate the androgen-responsive promoter in a ligand-dependent manner. Transcription-initiation sites of the mAR gene were identified by S1-nuclease protection experiments, and the functional activity of the promoter region was determined by transient expression of mAR promoter-CAT-reporter-gene constructs in HeLa cells. Structural analysis revealed the promoter of the mAR gene to be devoid of TATA/CCAAT elements. In addition, the promoter region is not remarkably (G + C)-rich. Potential promoter elements consist of a consensus Sp1 binding sequence and a homopurine stretch. The polyadenylation sites of mAR mRNA were identified by sequence similarity to the corresponding sites in the hAR mRNA. PMID- 1883337 TI - Production of platelet-activating factor is a component of the angiotensin II protein kinase C activation pathway in bovine adrenocortical cells. AB - Lyso-platelet-activating factor (lyso-PAF): acetyl-CoA acetyltransferase (EC 2.3.1.67) enzyme activity was characterized for the first time in bovine adrenocortical tissue. It was found to be associated with the microsomal membrane fraction, in which it exhibited a specific activity of 0.4 nmol/min per mg of protein and catalytic properties similar to those described in other cell types. The adrenocortical acetyltransferase activity was increased by 2-3-fold on incubation of the preparation with purified protein kinase C (PKC) under phosphorylating condition. This activation was optimal after 5 min of incubation and paralleled an increase in PKC-catalysed 32P incorporation into microsomal proteins. Both acetyltransferase activation and protein phosphorylation were dependent on the presence of Ca2+ and phospholipids, and were blocked in the presence of the potent PKC inhibitor H-7. In the intact adrenocortical cell, angiotensin II and a potent phorbol ester (phorbol 12-myristate 13-acetate) were able to rapidly induce an increase in the biosynthesis of PAF, which was mostly released into the extracellular medium. These data suggest that bovine adrenocortical lyso-PAF acetyltransferase may be regulated by a PKC-dependent activation pathway, whereas no evidence for an additional adrenocorticotropin/cyclic AMP-dependent stimulation process was obtained in this cell type. Bovine adrenocortical cell membrane preparations were shown to possess high-affinity PAF-binding sites (Kd approximately 0.5 nM). Altogether, these observations suggest that PAF production and release may play a role in the autocrine or paracrine control of adrenocortical cell activation. PMID- 1883339 TI - Algorithms for the derivation of Flux and Concentration Control Coefficients. AB - A computer program is described that derives the Flux and Concentration Control Coefficients for linear and branched metabolic pathways. The program prompts the user to enter a concise description of the metabolic pathway. From this description, the program constructs the appropriate equations in matrix form. The algorithm employed to obtain the symbolic determinants is described, and this algorithm also provides a convenient method for manual derivation of the Control Coefficients. The computer-based method will accommodate unlimited feed-forward and feed-backward loops and a maximum of two branches from each metabolite on the main pathway. The utility of the method is illustrated with a linear path with feed-forward and feed-backward loops, and with a substrate cycle as an example of a path with two branches. PMID- 1883338 TI - Cysteine-86 is not needed for the enzymic activity of glutathione S-transferase 3 3. AB - Recombinant glutathione S-transferase 3-3 expressed in Spodoptera frugiperda (SF9) cells with the use of a baculovirus expression system was modified with 1 mM-iodoacetamide. Amino acid analysis indicated that 0.79 +/- 0.15 cysteine residue was modified per enzyme subunit. The S-carbaminomethylated protein retains the GSH-conjugating activity. Glutathione S-transferase 3-3 modified with iodo[14C]acetamide was digested with Achromobacter proteinase I and the resulting peptides were separated by h.p.l.c. The modified peptides were pooled and further digested with Staphylococcus aureus V8 proteinase. Isotope-labelled peptides were isolated and collected for N-terminal sequence analysis. By this procedure, cysteine-86 was identified as the major S-carbaminomethylated residue. Verification of this findings came from the use of site-directed mutagenesis in which this cysteine was replaced by serine (C86S mutant). The C86S mutant is enzymically active. Therefore cysteine-86 is not needed for the conjugation of GSH with electrophilic compounds on glutathione S-transferase 3-3. PMID- 1883340 TI - Some questions and suggestions on the type references of the official nomenclature (IUB) for sialidase(s) and endosialidase. PMID- 1883341 TI - Isolation and partial characterization of antibody- and globin-enriched complexes from membranes of dense human erythrocytes. AB - In previous studies we have described a process whereby an erythrocyte in biochemical distress can initiate its own removal by macrophages of the reticuloendothelial system. This process involves the clustering of the integral membrane protein band 3 by denatured haemoglobin and the subsequent recognition of the exofacial poles of clustered band 3 and associated proteins by autologous antibodies. To determine whether this clearance pathway might mediate normal cell turnover, the fraction of normal erythrocytes containing the 0.5% densest cells, which are known to be destined for immediate removal, was isolated and characterized biochemically. This densest fraction was found to contain 6 times more membrane-bound globin (haemichromes) and 10 times more surface-bound autologous IgG than the other fractions containing cells of lower density. To determine whether the autologous IgG was physically associated with the haemichrome-stabilized membrane protein clusters, a procedure was developed for isolation and characterization of the microscopic aggregates. The isolated aggregates were found to contain a disulphide-cross-linked mixture of several membrane proteins, predominantly haemichromes, spectrin and band 3. Although the aggregates constituted only 0.09% of the total membrane protein, they still contained approximately 55% of the total cell-surface IgG. Since in control studies anti-(blood group A) antibodies, which are distributed randomly over the surface of type A cells, could not be recovered in the aggregate, we conclude that the autologous cell-surface IgGs were physically associated with the membrane protein clusters when they were co-isolated with them in our procedure. Thus the 640-fold enrichment of autologous IgG in the aggregates compared with regions of the membrane devoid of tightly clustered protein suggests that sites of integral protein clustering either are non-specifically sticky to IgG or are viewed as foreign or 'non-self' by the immune system and aggressively opsonized with IgG. PMID- 1883342 TI - Inhibition of glutathione S-transferase 3-3 by glutathione derivatives that bind covalently to the active site. AB - In all, 13 GSH derivatives have been synthesized and tested for their potency to inhibit glutathione S-transferase (GST) 3-3. All of these derivatives contained a reactive group that could potentially react with the enzyme active site. Best results were obtained with the phenylthiosulphonate derivative of GSH, GSSO2Ph. Preincubation of GST 3-3 with a 100 microM concentration of this inhibitor resulted in a time-dependent loss of activity: after 30 min at pH 6.5 and 25 degrees C, 51% of the activity was lost. At more alkaline pH, the activity is more rapidly inhibited: at pH 8.0 the 90%-inhibition level is already reached after 10 min preincubation. Separation of enzyme and excess unbound GSSO2Ph after preincubation by gel-filtration chromatography did not result in a reappearance of enzyme activity. If 100 microM-GSH was added to the preincubation mixture at pH 7.4, inhibition was almost completely prevented. Addition of S (hexyl)glutathione (20 microM) could delay the inhibition but, ultimately, not prevent it. The inhibited enzyme could be re-activated by addition of 10 mM-2 mercaptoethanol: 60 min after this thiol was added, the inhibited GST-3- activity was bacxk to the control level. GSH at the same concentration could not re activate the enzyme. On the basis of these results, on the known reactivity of thiosulphonate compounds, and on current knowledge about the amino acid residues involved in GST catalysis, a covalent modification of an active-site cysteine residue by mixed-disulphide formation between enzyme and the cosubstrate GSH is postulated. Information on the synthesis and characterization of the GSH derivatives is given in Supplementary Publication SUP 50166 (5 pages) which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1991) 273, 5. PMID- 1883344 TI - Computer program for the kinetic equations of enzyme reactions. The case in which more than one enzyme species is present at the onset of the reaction. AB - This paper presents an extension of the program developed by Varon, Havsteen, Garcia, Garcia-Canovas & Tudela [(1990) Biochem. J. 270, 825-828] for the expression of the transient-phase and steady-state kinetic equations of a general enzyme system in which the only enzyme species present at the onset of the reaction is the free enzyme. The program has been extended to situations in which more than one enzyme species may be present at the onset of the reaction. The program is given in Supplementary Publication SUP50165 (5 pages), which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1991) 273, 5. PMID- 1883345 TI - Relationship between the neural dysgenesis and increased production of class I MHC H-2Kk mRNA and protein in neurons of murine trisomy 16 fetuses. AB - Neuronal cells from murine trisomy 16 fetuses have increased levels of class I MHC H-2Kk. To determine whether this increased level of H-2Kk protein product resulted from an increased synthesis of mRNA, a 33 base antisense cDNA probe complementary to a region in exon 2 of the H-2Kk sequence (nucleotide 392-424) was synthesized. This probe was used to examine, by in situ hybridization and immunohistochemistry, the neural distribution of H-2Kk mRNA and protein product. A marked elevation of the H-2Kk mRNA and protein were localized in mts16 neuronal populations that were susceptible to dysgenesis. The results implicate the expression of the H-2Kk in the neuropathology of mts16 and its human counterpart, Down syndrome. PMID- 1883343 TI - Guanine-nucleotide- and adenine-nucleotide-dependent regulation of phospholipase D in electropermeabilized HL-60 granulocytes. AB - We have characterized the regulation of phospholipase D (PLD) in electropermeabilized HL-60 granulocytes in which endogenous phospholipids were pre-labelled with [3H]oleic acid. Treatment of these permeabilized cells with the non-hydrolysable GTP analogues guanosine 5'-[gamma-thio]triphosphate (GTP[S]) and guanosine 5'-[beta gamma-imido]triphosphate induced a sustained (near-linear for up to 60 min) accumulation of phosphatidic acid (PA). In the presence of ethanol a sustained production of phosphatidylethanol (PEt) was also observed. With increasing concentrations of ethanol, PEt formation increased, whereas PA formation declined; this indicated involvement of a PLD-type effector enzyme. The ability of GTP[S] to stimulate this PLD activity was Mg(2+)-dependent and was inhibited by GDP and its non-hydrolysable beta-thio analogue. Ca2+, at concentrations less than or equal to nM, had no effect on the GTP[S]-dependent PLD activity. However, higher concentrations of Ca2+ produced a significant potentiation of this activity. Inclusion of MgATP (greater than or equal to 0.1 mM), but not other nucleoside triphosphates, also induced a large potentiation of GTP[S]-dependent PLD activation. In the absence of guanine nucleotides, MgATP elicited no significant activation of PLD. Significantly, this effect of ATP was not mimicked by adenosine 5'-[beta gamma-methylene]triphosphate, a non hydrolysable ATP analogue. Rather, this analogue inhibited both basal and ATP potentiated GTP[S]-dependent PLD activity. This suggests that the ability of ATP to potentiate GTP[S]-dependent PLD activity involves phosphotransferase action rather than simple allosteric effects induced by adenine nucleotide binding. The absolute magnitude of the GTP[S]-dependent PLD activity which could be potentiated by MgATP was decreased by 90% when the permeabilized cells were preincubated for various times before addition of these stimulatory agents. This time-dependent loss of MgATP-induced potentiation was prevented when the permeabilized cells were preincubated in the presence of GTP[S]. These results demonstrate that electropermeabilized HL-60 granulocytes can be used to discriminate synergistic roles for a GTP-binding protein(s) and an ATP-dependent process (kinase?) in the regulation of phospholipase D activity. PMID- 1883346 TI - Selective antagonism of calcitonin-induced osteoclastic quiescence (Q effect) by human calcitonin gene-related peptide-(Val8Phe37). AB - Exposure of isolated rat osteoclasts to calcitonin (CT) leads to an abrupt cessation of cell motility (Q effect) followed by cell retraction (R effect). We have previously shown that these effects are mediated by two G proteins that appear to activate separate post-receptor pathways. The present study demonstrates that the Q but not the R effect of CT (0.006 microM) is abolished in the presence of human calcitonin gene-related peptide (CGRP)-(Val8Phe37) (0.5 microM), a fragment analogue of human CGRP. This selective antagonism suggests that the Q effect could result from an action of CT upon a site that is distinct from that producing the R effect. The former site ('amylin site') also appears to interact with related peptides, amylin and CGRP, whilst the latter site ('CT site') specifically interacts with CT. PMID- 1883347 TI - Differentiation of murine erythroleukemia cells by hexamethylenebisacetamide involves secretion and binding to membranes of a differentiation enhancing factor. AB - A protein factor previously shown to enhance terminal differentiation of transformed erythroid cells is synthesized by murine erythroleukemia cells and secreted in the early stages of differentiation induced by hexamethylenebisacetamide (HMBA). Secretion also occurs, constitutively, in the absence of inducer, from a murine erythroleukemia cell variant characterized by an accelerated response to HMBA. The protein factor binds to intact cells following addition of HMBA and enhances translocation of protein kinase C to the nuclear fraction. These results strongly support an important role for this natural protein factor in cell differentiation. PMID- 1883348 TI - Complementary DNA sequence of rabbit CAP18--a unique lipopolysaccharide binding protein. AB - CAP18 is a novel 18 kDa cationic protein [pI approximately 10] originally purified from rabbit granulocytes using as an assay the agglutination of lipopolysaccharide (LPS) coated erythrocytes. cDNA clones encoding CAP18 were isolated from a rabbit bone marrow cDNA library using a PCR generated oligonucleotide probe derived from the N-terminal amino acid sequence. The deduced amino acid sequence reveals a putative signal sequence of 29 amino acids and a mature protein of 142 amino acid residues. The predicted size of the encoded protein is 16.6 kDa with a pI of 10. There are no N-linked glycosylation sites. The CAP18 sequence bears no homology with other known LPS-binding proteins including human bacterial permeability increasing protein (BPI)(1) and rabbit LPS binding protein (LBP)(2). PMID- 1883349 TI - Cloning and sequencing of cDNA encoding human sepiapterin reductase--an enzyme involved in tetrahydrobiopterin biosynthesis. AB - A full-length cDNA clone for sepiapterin reductase, an enzyme involved in tetrahydrobiopterin biosynthesis, was isolated from a human liver cDNA library by plaque hybridization. The nucleotide sequence of hSPR 8-25, which contained an entire coding region of the enzyme, was determined. The clone encoded a protein of 261 amino acids with a calculated molecular mass of 28,047 daltons. The predicted amino acid sequence of human sepiapterin reductase showed a 74% identity with the rat enzyme. We further found a striking homology between human SPR and carbonyl reductase, estradiol 17 beta-dehydrogenase, and 3 beta-hydroxy-5 ene steroid dehydrogenase, especially in their N-terminal region. PMID- 1883350 TI - Isolation and sequencing of a cDNA clone encoding rat liver lysosomal cathepsin D and the structure of three forms of mature enzymes. AB - We isolated and sequenced a cDNA clone corresponding to the entire coding sequence of rat liver lysosomal cathepsin D. The deduced amino acid sequence revealed that cathepsin D consists of 407 amino acid residues (Mr 44,608) and the 20 NH2-terminal residues seem to constitute a cleavable signal peptide after which 44 amino acid residues follow as a propeptide. Two putative N-linked glycosylation sites and aspartic acid in the active site are as well conserved as those of human lysosomal cathepsin D. In the NH2-terminal sequence analysis of two isolated heavy chains of the mature enzyme, the termini were assigned as tryptophan (118th residue) and glycine (165th or 166th residue), respectively, hence demonstrates that the two heavy chains derive from a split of the single chain of cathepsin D at position between 117th and 118th or between 164th and 165th or 165th and 166th amino acids. We conclude that cathepsin D in rat liver lysosomes is a mixture of three forms composed of a single and two two-chain forms. However, the amounts of the two two-chain forms are low compared with that of the single chain form. Densidometric determination after SDS-PAGE revealed that the two two-chain forms account for less than 5% of the single chain form. There is a 82% similarity in amino acid level between rat and human liver lysosomal cathepsin D. PMID- 1883351 TI - O-hydroxyphenylacetaldehyde: a major novel metabolite of coumarin formed by rat, gerbil and human liver microsomes. AB - A major novel coumarin metabolite was isolated from rat hepatic microsomal incubations by high-performance liquid chromatography. In the presence of a rat liver cytosolic fraction and NADH it was rapidly metabolized to O hydroxyphenylethanol. The metabolite co-chromatographed with an authentic sample of O-hydroxyphenylacetaldehyde and its identity was confirmed by mass spectral analysis. The formation of O-hydroxyphenylacetaldehyde from coumarin was NADPH dependent. It was the major metabolite formed by rat, gerbil and human liver microsomes at a coumarin concentration of 1mM. PMID- 1883352 TI - Effect of antiserum to a 99 kDa polypeptide on the uptake of taurocholic acid by rat ileal brush border membrane vesicles. AB - A 99 kDa polypeptide in rat ileal brush border membrane (BBM), regarded as a component of the active bile acid transport system on account of photoaffinity labeling, has been purified by affinity chromatography and preparative gel electrophoresis and utilized as an immunogen for raising polyclonal antibody. Immune serum, but not preimmune serum, specifically recognized a single band of 99 kDa protein on immunoblots of ileal and renal BBM. In contrast, no reactivity was observed with proteins in jejunal BBM. This polyclonal antibody, compared with preimmune serum and anticytosolic bile acid binding protein (14 kDa) serum, significantly inhibited the Na+ dependent uptake of [3H] taurocholate by BBM vesicles (p less than 0.01). [14C] D-glucose uptake by BBM vesicles was not influenced by the immune serum (p less than 0.01). Thus, these studies provide further support for the specific role of a 99 kDa protein in ileal BBM bile acid transport. PMID- 1883353 TI - Temporal regulation of tobacco mosaic virus-induced phosphorylation of a host encoded protein. AB - The in vitro and in vivo phosphorylation of a plant encoded protein (p68) associated with dsRNA-dependent protein kinase activity was stimulated at specific time intervals following infection by tobacco mosaic virus or electroporation with dsRNA. The level of p68 phosphorylation in infected and mock inoculated protoplasts did not differ significantly until 6 hr. post-infection, when the basal level of phosphorylation increased 2-3 fold in infected protoplasts. Maximum phosphorylation of p68 occurred between 8-12 hr post infection and then declined but, at least until 72 hr. post-infection, it was significantly greater than in mock inoculated protoplasts. PMID- 1883354 TI - Effect of parathyroid hormone on release of interleukin 1 and interleukin 6 from cultured mouse osteoblastic cells. AB - This study was undertaken to examine the possibility that parathyroid hormone promotes the production of interleukin 1 and 6 in MC3T3-E1 osteoblastic cells derived from mouse calvaria. The cells were incubated in serum-free medium with or without synthetic human parathyroid hormone(1-34). The concentrations of interleukin 1 and 6 in the culture medium were determined by using specific bioassay. The cells cultured without parathyroid hormone for 24 hr released both of interleukins, and parathyroid hormone stimulated the release in a dose dependent manner. When the cells were cultured with 10(-6) M parathyroid hormone, the release of both interleukins from the cells remained higher than control up to 144 hr. These results suggest that interleukin 1 and 6 release stimulated by parathyroid hormone may be involved in the bone resorbing activity of the hormone. PMID- 1883355 TI - Quantitative measurement of extra-renal renin mRNA by polymerase chain reaction. AB - We established a simplified method of the quantitative measurement of extra-renal renin messenger RNA using polymerase chain reaction system. We could detect the renin messenger RNA in the kidney, heart, aorta and adrenal gland from a single RNA sample obtained from a Wistar-Kyoto rat. In the kidney, heart, aorta and adrenal gland, the contents of renin messenger RNA were found to be 55.8 +/- 17.8, 0.15 +/- 0.05, 0.11 +/- 0.03 and 0.16 +/- 0.07 pg/micrograms of total RNA (n = 5, mean +/- s.d.), respectively. The present method is very useful to study the extra-renal renin-angiotensin system. PMID- 1883356 TI - Overexpression of a beta-galactoside binding protein causes transformation of BALB3T3 fibroblast cells. AB - Overexpression of an animal lectin, rat beta-galactoside binding protein (GBP) in mouse BALB3T3 fibroblast cells by stable introduction of a GBP cDNA expression plasmid results in the acquisition of transformed phenotype which includes a loss of anchorage dependence, reduced contact inhibition, colony formation in soft agar, and tumor formation in nude mice. The transformation depends on the level of the expression of both GBP and TGF gamma 2 activities confirming that both activities are ascribable to a single bifunctional protein TGF gamma 2/GBP. The results indicate that GBP acts as a growth regulator and is directly involved in regulation of cell proliferation. PMID- 1883357 TI - A novel cationic liposome reagent for efficient transfection of mammalian cells. AB - A novel cationic derivative of cholesterol, 3 beta [N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol), has been synthesized and used to prepare sonicated liposomes with dioleoylphosphatidylethanolamine. This novel cationic liposome reagent facilitates efficient DNA mediated transfection in A431 human epidermoid carcinoma cells, A549 human lung carcinoma cells, L929 mouse fibroblast cells, and YPT minipig primary endothelial cells. The activity was greater than that of a commercial reagent, Lipofectin, and was approximately 4 fold less toxic than Lipofectin when assayed with A431 cells. The reagent is easy to synthesize and stable for at least 6 weeks. PMID- 1883359 TI - Purification of large neuromedin N (NMN) from canine intestine and its identification as NMN-125. AB - A large molecular form of neuromedin N (NMN), a neurotensin (NT)-related peptide, was purified to homogeneity from canine ileal mucosa. The amino acid sequence of its N-terminal 20 residues was found to be SDSEEEMKALEADLLTNMHT, which is identical to residues 24-43 of the cDNA-predicted NT/NMN precursor. Prior work had indicated that the NMN moiety was located at the C-terminus of large NMN. Having now defined both the N-terminus and C-terminus of large NMN, we note that this molecule must be comprised of 125 amino acids (including residues 24-148 of prepro NT/NMN) and we suggest that it be named NMN-125. This information also defines the signal peptide cleavage site as the cysteine-serine bond within the precursor. The amino acid composition of the isolated peptide and its molar extinction coefficient for absorbance at 280 nm were similar to those for the 24 148 segment of prepro NT/NMN. However, the empirically determined molecular weight (17 kDa) and the isoelectric point (pI = 5.4) were slightly higher than those predicted solely from the peptide's amino acid content (14.43 kDa and pI = 4.65, respectively). In total, these results indicate that the major NMN-related peptide found in canine ileum is 125 residues in length, extending from the putative signal peptide to the C-terminus of NMN, and that it might contain non amino acid substituents. PMID- 1883358 TI - SF-B that binds to a negative element in glutathione transferase P gene is similar or identical to trans-activator LAP/IL6-DBP. AB - We have previously identified a silencer (negative enhancer) in glutathione transferase P (GST-P) gene which is strongly and specifically induced during hepatocarcinogenesis of the rat. At least three trans-acting factors bind to multiple cis-elements located in this silencer. One of these factors, SF-B (Silencer Factor B) specifically binds to GPS1 (GST-P Silencer 1) and has been cloned by a Southwestern protocol. Analysis of DNA and deduced amino acid sequence reveals that SF-B clone is most likely identical to an IL-6 inducible trans-activator LAP/IL6-DBP. Binding efficiency of SF-B to GPS1 is indistinguishable from that to IL6-responsive element found in C-reactive protein gene. The possibility that SF-B/LAP/IL6-DBP functions as a dual positive and negative regulator is discussed. PMID- 1883360 TI - Neuropeptide Y stimulates prostacyclin production in porcine vascular endothelial cells. AB - We investigated the effects of neuropeptide Y on the prostacyclin production of cultured porcine aortic endothelial cells by measuring the stable metabolite of prostacyclin, 6-keto-prostaglandin F1 alpha, by radioimmunoassay. Neuropeptide Y induced dose- and time-dependent stimulation of prostacyclin production by cultured porcine aortic endothelial cells. The lowest stimulatory concentration of neuropeptide Y was 10(-8) M and maximal response, a 2.8 fold rise, was obtained with 10(-6) M. The stimulation lasted at least 24 h. The effect was associated with the stimulation of arachidonic acid release. Our data suggest that neuropeptide Y may inhibit the development of atherosclerosis by stimulating prostacyclin synthesis. PMID- 1883361 TI - Prokaryotic expression of the thyrotropin receptor and identification of an immunogenic region of the protein using synthetic peptides. AB - Graves' disease is characterized by hypersecretion of thyroid hormones due to binding of autoantibodies to the thyrotropin receptor (TSHR). In order to study immunological aspects of the TSHR we expressed the extracellular domain of the rat TSHR (ETSHR) as a fusion protein with beta-galactosidase in a prokaryotic system. The identity of this ETSHR-fusion protein was confirmed by Western blot, using antibodies to synthetic peptides derived from TSHR. Patients' sera reacted to a significantly greater extent with the affinity purified ETSHR relative to control sera. Similarly, sera from patients with Graves' disease displayed significant reactivity with only one of five peptides, RH2 (residues 352-366), when compared with normal sera. These data, together with the predicted hydrophilicity of the peptide RH2, suggest that amino acids 352-366 which lie within one of the unique regions of the extracellular domain of the TSHR may be important for antibody binding. PMID- 1883362 TI - The effect of extracellular matrix interactions on morphologic transformation in vitro. AB - There is emerging evidence that the structure and function of a cell is dependent in part on the contacts that cells make with the extracellular matrix. We report here the effect of extracellular matrices secreted from both normal and tumor cells have on the structure of normal rat kidney epithelial cells. Normal rat kidney cells plated on the basement membrane secreted by tumor cells adopt a morphology and phenotype which closely resembles a Kirsten-ras transformed normal rat kidney cell. This morphologic transformation was not observed for cells plated on individual extracellular matrix components or on basement membrane secreted by normal placenta cells. This suggests that tumor derived basement membrane has unique characteristics which may cause morphologic transformation of normal rat kidney cells. PMID- 1883363 TI - Modifications of the intermediate filament and nuclear matrix networks by the extracellular matrix. AB - The tissue matrix system is a dynamic, interacting structural network directly linking the nuclear matrix, cytoskeleton and the extracellular matrix. We report here that interaction of normal rat kidney epithelial cells (NRK) and Kirsten-ras transformed rat kidney cells, with an extracellular matrix secreted by tumor cells, causes modifications to the protein composition of the intermediate filament and nuclear matrix networks. The matrix networks are different between normal and transformed cells; however, these alterations by the tumor extracellular matrix are similar in both cell types. These data represent the first report that modification of the extracellular matrix environment can have an effect on the protein composition of the nuclear matrix. PMID- 1883364 TI - Site-specific mutagenesis of human follistatin. AB - Follistatin is a monomeric protein originally discovered in ovarian follicular fluid as a suppressor of pituitary follicle-stimulating hormone (FSH) secretion, and later identified as a binding protein for activin. To explore the role of the Asn-linked carbohydrate chains on the follistatin molecule in regard to the inhibition of FSH secretion and activin binding ability, site-specific mutations were introduced at either or both of the two potential Asn-linked glycosylation sites of human follistatin with 315 amino acids (hFS-315). The three types of follistatin mutants were expressed individually in Chinese hamster ovary cells. When tested for their ability to inhibit FSH secretion and to bind activin, each mutant was found to have a similar property as the non-mutated recombinant hFS 315, suggesting that glycosylation of the follistatin molecule has no effect in these functions. However, a two amino acid insertion in between the second and the third amino acid residues in hFS-315 caused the resulting compound to lose completely its inhibitory activity on FSH secretion from the pituitary as well as its binding ability to activin. This finding suggests that the amino-terminal region of the follistatin molecule is critical for both of these functions. PMID- 1883365 TI - The contribution of the macrophage receptor for oxidized LDL to its cellular uptake. AB - Oxidized LDL (Ox-LDL) was shown to be taken up by macrophages via several receptors including the acetyl-LDL(Ac-LDL), the LDL, and the Ox-LDL receptors. Cellular uptake and degradation of Ox-LDL could be dissociated from that of LDL and Ac-LDL as demonstrated by using macrophages that lack the LDL or the Ac-LDL receptors. In J-774 A.1 macrophage-like cell line unlabeled Ox-LDL reduced the 125I-Ox-LDL by up to degradation of 91% whereas unlabeled Ac-LDL and native LDL reduced 125I-Ox-LDL degradation by only 51% and 23%, respectively. Analysis of macrophage degradation of 125I-Ox-LDL in the presence of 30-fold excess concentration of LDL + Ac-LDL (to block uptake of 125I-Ox-LDL via the LDL and the Ac-LDL receptors) revealed that cellular degradation via the Ox-LDL receptor could account for 45% of the macrophage uptake of Ox-LDL. PMID- 1883366 TI - 13C NMR study of hepatic pyruvate carboxylase activity in tumor rats. AB - Alanine and lactate, as major gluconeogenic substrates, must be converted into oxaloacetate by way of pyruvate carboxylase before their entry into gluconeogenesis. Although it is well known that hepatic gluconeogenesis from these substrates is increased in tumor hosts, the involvement of pyruvate carboxylase has not been demonstrated. In the present study, we examined pyruvate carboxylase activity in the perfused livers of tumor rats using 13C NMR spectroscopy with [3-13C]-alanine as the gluconeogenic substrate. A substantial increase in hepatic [3-13C]-aspartate production was found in the tumor rats. Since aspartate accumulation directly reflects fluxes of alanine through pyruvate carboxylase, the observed increase in hepatic production of [3-13C]-aspartate in tumor rats indicates that pyruvate carboxylase activity is significantly enhanced. PMID- 1883367 TI - 1H NMR study of the sugar pucker of 2',3'-dideoxynucleosides with anti-human immunodeficiency virus (HIV) activity. AB - The sugar ring conformations of 2',3'-dideoxyribosyladenine (ddA), 2',3' dideoxyribosylcytosine (ddC), 2',3'-dideoxyribosylguanine (ddG), 2',3' dideoxyribosylhypoxanthine (ddI), 3'-azido-2',3'-dideoxyribosylthymine (AZT), 3' azido-2',3'-dideoxyribosyluracil (AZU) and 3'-fluoro-2',3'-dideoxyribosylthymine (FddT) have been investigated by 1H NMR spectroscopy. While the sugar ring in FddT exists almost totally in C2'-endo geometry, other nucleosides show equilibrium between sugar puckers of C3'-endo family (N-type) and C2'-endo family (S-type). For unsubstituted dideoxynucleosides C3'-endo conformer is favoured (congruent to 75%), whereas for AZT and AZU both the conformers have almost equal populations. Unlike X-ray diffraction studies, the NMR results do not support the suggestion that C3'-exo sugar puckers are desirable for the anti-HIV activity of these nucleosides. PMID- 1883368 TI - Overexpression of the actin gene is associated with the morphogenesis of Candida albicans. AB - A progressive increase in the synthesis of actin mRNA was observed by Northern blot analysis, when cells were induced to form germ tubes at 37 degrees C by N acetyl-D-glucosamine. Presence of trifluoperazine, a calmodulin inhibitor, or incubation of cells at 25 degrees C, or by replacing N-acetyl-D-glucosamine with glucose which inhibited germ tube formation lowered this synthesis. Furthermore, in vitro translation of total RNA revealed an increase in the synthesis of actin (45 kDa) during germ tube formation. These results suggest for the first time that the expression of actin gene is regulated during morphogenesis of C. albicans. PMID- 1883370 TI - 1-bromoalkanes as new potent nontoxic glutathione depletors in isolated rat hepatocytes. AB - The effect of 1-bromlalkanes on intracellular glutathione (GSH) was studied in freshly isolated rat hepatocytes. Treatment of cells with bromoalkanes depleted cellular GSH levels without causing cytotoxicity. The extent of GSH depletion was directly proportional to the concentration and increasing chain length of 1 bromoalkanes (C2-C7). Bromoheptane (100 microM) depleted GSH by 87% in 30 mins which remained depleted for the 4 hr study period without causing cytotoxicity. A 30 fold higher concentration of bromoheptane was required before cytotoxicity ensued. Bromoheptane would therefore be particularly useful for studying the role of GSH in modulating xenobiotic cytotoxicity. PMID- 1883369 TI - Cloning and characterization of a lignin peroxidase gene from the white-rot fungus Trametes versicolor. AB - Six putative lignin peroxidase (LIP) genes were isolated from a lambda EMBL3 phage library of the white-rot fungus, Trametes versicolor, using the Phanerochaete chrysosporium LIP cDNA CLG5 as the probe. Sequence analysis of one of the genes, VLG1, showed that its coding region is interrupted by six small introns (49-64 bp) and that it encodes a mature LIP protein (341 aa; Mr: 36,714) that is preceded by a 25 aa signal sequence. This protein has a relatively high degree of aa homology to the N-termini of the LIP proteins purified from T. versicolor and has an aa homology of 55-60% to the LIP proteins of P. chrysosporium, which is comparable to that found between P. chrysosporium and Phlebia radiata LIP proteins. PMID- 1883371 TI - Post-translational reduction of cytochrome P450IIE by CCl4, its substrate. AB - The molecular mechanism of cytochrome P450IIE reduction by CCl4 was reexamined by measuring its enzyme activity, immunoreactive protein contents, and mRNA levels. Aniline hydroxylase and the amounts of immunoreactive P450IIE were rapidly decreased in a time-dependent manner after a single dose of CCl4. No changes were observed in the amounts of immunoreactive P450IIC and P450IA despite significant decreases decrease in their catalytic activities. However, the decreases in P450IIE enzyme activity and immunoreactive protein by CCl4 were not accompanied by a decline in its mRNA level. The data thus suggested a post-translational reduction of P450IIE by CCl4, probably due to specific destruction of the P450IIE protein by its own substrate rather than heme moiety. PMID- 1883372 TI - Transmembrane signalling by the N-formyl peptide receptor in stably transfected fibroblasts. AB - We investigated the requirement for N-formyl peptide receptor-mediated transmembrane signalling in transfected mouse fibroblasts that express the receptor. Stably transfected cells displayed specific binding for N-formyl-Met Leu-[3H]Phe with a dissociation constant of 3 nM. The cells responded to ligand stimulation with mobilization of calcium from intracellular stores. Calcium mobilization was ligand dose-dependent (EC50 = 3 nM fMet-Leu-Phe) and could be inhibited by pertussis toxin treatment. These results provide the first demonstration that expression of the single-chain N-formyl peptide receptor in mouse fibroblasts is sufficient for mediating ligand-induced early transmembrane signalling events, which do not appear to require other neutrophil-specific cellular components. PMID- 1883373 TI - Electrophoretic separation of S. pombe chromosomes in polyacrylamide solutions using a constant field. AB - Previous electrophoretic separations of megabase (Mb) sized DNA have been achieved in pulsed electric fields, using agarose gel as a matrix. The present study demonstrates separations of Mb sized DNA due to a retardation of migration in proportion to the concentration of uncrosslinked polyacrylamide of 5 x 10(6) molecular weight, using a constant electric field. Potentially, the method should be applicable to large DNA in general, greatly reducing the instrumental complexity of such separations and rendering them compatible with capillary electrophoresis apparatus. PMID- 1883374 TI - Involvement of protein kinase C in Ca(2+)-independent contraction of rat uterine smooth muscle. AB - The contribution of protein kinase C to the contraction by oxytocin of rat uterine longitudinal smooth muscle in Ca(2+)-free solution was investigated. Immunological analysis revealed that type II (beta) and III (alpha) protein kinase C subspecies were present in rat uterine smooth muscle. The pretreatment of a diacylglycerol kinase inhibitor R59022 to accumulate diacylglycerol potentiated the Ca(2+)-independent contraction. The contractile activity was diminished with the depletion of protein kinase C, when the contraction was evoked repeatedly by oxytocin during the prolonged exposure to a tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate. These results suggested the involvement of protein kinase C in oxytocin-induced contraction in Ca(2+)-free solution. PMID- 1883375 TI - Excitation-contraction uncoupling during ischemia in the blood perfused dog heart. AB - The bioluminescent of Ca(2+)-indicator, aequorin, was loaded into the left ventricular apex of blood-perfused hearts from 13 dogs for simultaneous recording of left ventricular pressure and intracellular calcium levels. During a 2 minute period of ischemia, systolic and diastolic pressures significantly decreased. In contrast, these pressure changes were associated with an increase in both systolic and diastolic calcium reaching a maximum diastolic value of 0.59 microM and a systolic value of 1.11 microM. This apparent dissociation between pressure and [Ca2+]i supports the hypothesis that changes in myofilament Ca2+ responsiveness are of major importance in modulating contractility during ischemia in large mammalian hearts. PMID- 1883376 TI - Inhibitory effects of dicyclohexylcarbodiimide on spinach cytochrome b6-f complex. AB - The electron transfer activity of purified cytochrome b6-f complex of spinach chloroplast is inhibited by dicyclohexylcarbodiimide (DCCD) in a concentration and incubation time dependent manner. The maximum inhibition of 75% is observed when 300 mole of DCCD per mole of protein (based on cytochrome f) is incubated with cytochrome b6-f complex at room temperature for 40 min. The inhibition of the complex is not due to the formation of cross links between subunits but due to the modification of carboxyls. The amount of DCCD incorporation is directly proportional to the activity loss, suggesting that some carboxyl groups in the complex are directly or indirectly involved in the catalytic function. The incorporated DCCD is located mainly at cytochrome b6 protein. The partially inhibited complex shows the same H+/e-ratio as that of the intact complex when embedded in phospholipid vesicles. PMID- 1883377 TI - The presence of sequence-specific protein binding sites correlate with replication activity and matrix binding in a 1.7 Kb-long DNA fragment of the chicken alpha-globin gene domain. AB - Several recognition sites for novel sequence-specific DNA-binding proteins were found at the 5'-side of the chicken alpha-globin gene domain in a 1.7 Kbp DNA fragment. This fragment includes the replication origin, a non tissue-specific transcriptional enhancer, a DNAse I hypersensitive site and a permanent site of DNA attachment to the nuclear matrix. Most of the identified protein binding sites differ from previously known consensus sequences. Two sites coincide with MARs located at the 5'-end of the 1.7 kbp fragment. The proteins interacting with these two recognition sites were observed only in proliferating cells and were virtually absent in the extracts obtained from the nonreplicating differentiated form of the same cells. One of them seems to belong to the GATA protein family, but its presence in nuclear extracts correlates with cell proliferation rather than expression of the domain. PMID- 1883378 TI - Hepoxilin A3 induces heat shock protein (HSP72) expression in human neutrophils. AB - In this paper we show that hepoxilin A3 induces the expression of heat shock protein expression in human neutrophils at a concentration of 100 nM using Western blotting techniques employing the use of a commercial monoclonal antibody to HSP72. No regiospecificity was observed as the 8S enantiomer of HxA3 was as active as the 8R enantiomer of HxA3. Comparison of the effects of HxA3 with 12S HETE and PGA1 indicated that HxA3 was as effective as 12S-HETE although PGA1 was essentially inactive at the same concentration used for these 12-lipoxygenase products. PMID- 1883379 TI - Synthesis and secretion of cobalamin binding proteins by opossum kidney cells. AB - Opossum kidney epithelial cells synthesize and secrete two Cobalamin (Cbl) binding proteins of Mr 66,000 and 43,000. When grown on culture inserts, the apical medium contained both these proteins while the basolateral medium contained only the 43 kDa Cbl binder. Colchicine, a microtubule disruptive drug, increased two fold the apical but not the basolateral secretion of the Cbl binding proteins. Although the opossum Cbl binders did not cross react with anti serum raised to Cbl binders from other species, the identity based on Cbl binding and size suggest that the 66 kDa and 43 kDa proteins are haptocorrin and transcobalamin II. PMID- 1883380 TI - Antiproliferative effect of 1,25-dihydroxyvitamin D3 and its analogs on human colon adenocarcinoma cells (CaCo-2): influence of extracellular calcium. AB - Depending on culture in either "low Ca++" (0.25 mM) or "normal Ca++" (1.8 mM) medium, human colon adenocarcinoma-derived CaCo-2 cells exhibit differential sensitivity to the antiproliferative action of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and of two side-chain modified analogs, 1,25S,26-trihydroxy-delta 22-vitamin D3 (Ro 23-4319) and 1,25-dihydroxy-delta 16-23yne-vitamin D3 (Ro 23 7553). CaCo-2 cells cultured under low Ca++ conditions exhibit a high proliferative potential, and in these cells, all vitamin D compounds under investigation significantly inhibit [3H]thymidine incorporation into cellular DNA at greater than or equal to 10(-10) M. The rank order of biopotency is: Ro 23 7553 greater than or equal to Ro 23-4319 greater than 1,25(OH)2D3. At 1.8 mM Ca++, only Ro 23-7553 is able to inhibit proliferation of CaCo-2 cells. Parallel to their antiproliferative action, all three vitamin D compounds stimulate akaline phosphatase activity in CaCo-2 cells, indicating their ability to induce differentiated functions at the same time as they reduce neoplastic cell growth. PMID- 1883381 TI - Amphiregulin-associated protein: complete amino acid sequence of a protein produced by the 12-0-tetradecanoylphorbol-13-acetate-treated human breast adenocarcinoma cell line MCF-7. AB - Amphiregulin-associated protein (ARAP) was purified from serum-free conditioned medium of MCF-7, human breast carcinoma cells, treated with 12-0 tetradecanoylphorbol-13-acetate (TPA). ARAP is a single-chain, extremely hydrophilic, heparin-binding protein. Its apparent molecular weight is approximately 21,500 as assessed by gel chromatography and approximately 15,500 as determined by polyacrylamide gel electrophoresis. The complete amino acid sequence of ARAP was determined. The larger form contains 123 amino acids, whereas a shorter form is missing two amino acids at the amino-terminal. ARAP contains 10 cysteines and 30 basic amino acids (23 lysines and 7 arginines). ARP sequence has been found to be identical to protein encoded by human MK gene. PMID- 1883382 TI - Casein kinase I in bovine sperm: purification and characterization. AB - A highly purified preparation of sperm casein kinase I was obtained by sequential chromatography with phosphocellulose, gel filtration on sephacryl S-300, Affi-gel blue and DEAE-Cellulose. The chromatographic behavior and properties of the enzyme suggest that the sperm enzyme is similar to casein kinase I from other tissues. Antibodies against calf thymus casein kinase I cross-react with the sperm enzyme. A special feature of the sperm enzyme is that the activity is stimulated by spermine. PMID- 1883383 TI - Evidence for sulfite as an essential metabolite for human peripheral lymphocytes. AB - Sulfite has been identified as an essential metabolite by means of growth studies using a chemically-defined, protein-free medium for culture of human peripheral lymphocytes. Sulfite reduced the amount of cysteine required for optimum growth by at least four-fold. In some subjects, sulfite stimulated growth even in the presence of optimal amounts of cysteine indicating that lymphocytes of some individuals are unable to convert cysteine to sulfite in adequate amounts. PMID- 1883384 TI - A deficiency of vitamin B6 is a plausible molecular basis of the retinopathy of patients with diabetes mellitus. AB - Eighteen patients with diabetes mellitus, some of whom had variously retinopathy, pregnancy, and the carpal tunnel syndrome, and were variously treated with steroids and vitamin B6, have been overviewed for periods of 8 months to 28 years. We have established an association of a deficiency of vitamin B6 with diabetes by monitoring the specific activity of the erythrocyte glutamic oxaloacetic transaminase and again by the association with the carpal tunnel syndrome (C.T.S.). It has been known for a decade that C.T.S. is caused by a B6 deficiency. The absence of retinopathy in vitamin B6-treated diabetic patients over periods of 8 months - 28 years appears monumental. These observations are like discovery and constitute a basis for a new protocol to establish the apparent relationship of a deficiency of vitamin B6 as a molecular cause of diabetic neuropathy. Blindness and vision are so important that the strength or weakness of the observations are not important; the conduct of a new protocol is important. PMID- 1883385 TI - Cathepsin B and L activities in isolated osteoclasts. AB - Cathepsin B and L activities were examined with chicken osteoclasts isolated by sequential filtration and inhibitors were added to disaggregated rat osteoclasts on cortical bovine bone. Z-Phe-Phe-CHN2, a selective inhibitor of cathepsin L, at 1, 5, and 10 microM, inhibited bone resorption by rat osteoclasts 50, 85, and 100 per cent and, in chicken osteoclasts, cathepsin L activity was comparably inhibited. Cathepsin L in avian osteoclasts was also 25-fold higher than cathepsin B. Chicken osteoclasts treated with Z-Phe-Ala-CHN2, a generalized cysteine proteinase inhibitor, had both cathepsins inhibited to the same extent. Cathepsin L may play a key role in resorption. PMID- 1883386 TI - Molecular dissection of cholinergic binding sites: how do snakes escape the effect of their own toxins? AB - Snakes have evolved a novel binding site demonstrating selective biorecognition. The snake nicotinic acetylcholine receptor is sensitive to acetylcholine while resistant to the effect of the lethal neurotoxins secreted in their own venom. By subjecting recombinant binding sites to point mutagenesis, biochemical analyses and NMR spectroscopy the binding characteristics of three cholinergic ligands have been measured. The amino acid residue at position 189 has been found to be of particular importance to toxin binding. PMID- 1883387 TI - Genistein inhibition of the growth of human breast cancer cells: independence from estrogen receptors and the multi-drug resistance gene. AB - The effect of isoflavones on the growth of the human breast carcinoma cell lines, MDA-468 (estrogen receptor negative), and MCF-7 and MCF-7-D-40 (estrogen receptor positive), has been examined. Genistein is a potent inhibitor of the growth of each cell line (IC50 values from 6.5 to 12.0 micrograms/ml), whereas biochanin A and daidzein are weaker growth inhibitors (IC50 values from 20 to 34 micrograms/ml). The isoflavone beta-glucosides, genistin and daidzin, have little effect on growth (IC50 values greater than 100 micrograms/ml). The presence of the estrogen receptor is not required for the isoflavones to inhibit tumor cell growth (MDA-468 vs MCF-7 cells). In addition, the effects of genistein and biochanin A are not attenuated by overexpression of the multi-drug resistance gene product (MCF-7-D40 vs MCF-7 cells). PMID- 1883388 TI - The monomer of pyruvate kinase, subtype M1, is both a kinase and a cytosolic thyroid hormone binding protein. AB - Using a T7 expression system, the monomer of rat pituitary pyruvate kinase, subtype M1 (PKM1), was overexpressed in Escherichia coli and purified to homogeneity. The monomeric p58-M1 has intrinsic enzymatic activity with a Vmax of 79 +/- 20 units/mg and Km's for ADP and PEP of 1.43 +/- 0.76 and 0.14 +/- 0.07 mM, respectively. The monomer binds 3,3',5-triiodo-L-thyronine (T3) with Ka = 1.5 x 10(7) M-1. The order of analog specificity is L-T3 greater than L-thyroxine greater than D-T3 greater than 3'-isopropyl-3,5-diiodo-L-thyronine greater than or equal to 3',5',3-triiodo-L-thyronine. In contrast, tetrameric PKM1 lacks T3 binding activity. The kinase activity of p58-M1 is inhibited by T3 and its analogs in a concentration-dependent manner with the order of inhibitory activity similar to that of binding activity. This inhibition, however, is reversed by the addition of fructose 1,6-bisphosphate. p58-M1 is the second PK isoenzyme monomer to be identified as having thyroid hormone binding activity. PMID- 1883389 TI - Initial description of a tumor enhancing activity produced by murine splenocytes. AB - We have shown that certain murine tumors grow more slowly and spread less readily in immune deficient animals. We have also demonstrated that immunologic factors explain certain aspects of this difference. In the work presented we demonstrate that a subpopulation of splenocytes produce a factor(s) that enhances tumor cell proliferation in vitro. We also describe an in vitro model to determine the level of tumor stimulatory activity. We found that the tumor cell growth-enhancing activity (TEA) is heat stable but sensitive to trypsin digestion, low pH and beta mercaptoethanol. TEA production is found to be insensitive to mitogen stimulation such as concanavalin A, lipopolysaccharide, and phytohemagglutinin. Among the known growth factors and interleukins we have tested (interleukin 1-7, basic FGF, EGF, TGF-beta PDGF, GM-CSF, and MCSF), none appear to account for TEA activity. PMID- 1883390 TI - Purification of recombinant human tumor necrosis factor precursor from Escherichia coli. AB - To study its biological functions, tumor necrosis factor precursor (proTNF) with a molecular size of 26-KDa was obtained as a recombinant protein from Escherichia coli. The recombinant proTNF was successfully accumulated in the insoluble form, corresponding to about 10-15% of total E. coli proteins. Solubilization, gel filtration and anion exchange chromatography were performed under denatured conditions followed by dialysis in phosphate-buffered saline. These processes removed most of the contaminating bacterial proteins, yielding proTNF with a purity of about 70-80%. This recombinant proTNF is expected to be useful for functional studies on activated macrophages with membrane integrated proTNF. PMID- 1883391 TI - Immunoglobulins from Graves' disease patients interact with different sites on TSH receptor/LH-CG receptor chimeras than either TSH or immunoglobulins from idiopathic myxedema patients. AB - To examine the identity of binding sites for thyrotropin (TSH) and thyroid stimulating antibodies (TSAbs) associated with Graves' disease, we constructed eight human TSH receptor/rat LH-CG receptor chimeras. Substitution of amino acid residues 8-165 of the TSH receptor with the corresponding LH-CG receptor segment (Mc1 + 2) results in a chimera which retains high affinity TSH binding and the cAMP response to TSH but loses both the cAMP response to Graves' IgG and Graves' IgG inhibition of TSH binding. Two of three IgGs from idiopathic myxedema patients which contain thyroid stimulation blocking antibodies (TSBAbs) still, however, react with this chimera. Chimeras which substitute residues 90-165 (Mc2) and 261-370 (Mc4) retain the ability to interact with TSH, Graves' IgG, and idiopathic myxedema IgG. The data thus suggest that residues 8-165 contain an epitope specific for TSAbs and that TSH receptor determinants important for the activities of TSAbs and TSH are not identical. Further, binding sites for TSBAbs in idiopathic myxedema may be different from receptor binding sites for both Graves' IgG TSAb as well as TSH and may be different in individual patients. PMID- 1883392 TI - GLP-1(7-36)amide-stimulated insulin secretion in rat islets is sodium-dependent. AB - We examined the Na(+)-dependency of the effects of GLP-1(7-36)amide in normal, overnight cultured rat islets. It was found that GLP-1(7-36)amide stimulated insulin secretion, 45Ca(2+)-efflux, and 86Rb(+)-efflux from prelabelled islets. All these effects were abolished by omitting Na+ from the medium and replacing it with N-methyl-glucamine. This suggests that GLP-1(7-36)amide stimulates insulin secretion by depolarizing the beta-cells by increasing their permeability to Na+. PMID- 1883393 TI - Compound heterozygosity for mutant hepatic lipase in familial hepatic lipase deficiency. AB - In a kindred with three hyperlipidemic subjects who had premature atherosclerosis and complete deficiency of hepatic lipase activity, we had previously identified a novel structural hepatic lipase gene variant. We now report the identification of three more hepatic lipase gene mutations in this family and demonstrate that compound heterozygosity for two hepatic lipase mutations (designated S267F and T383M) underlies hepatic lipase deficiency. PMID- 1883394 TI - Effects of androgen on intracellular calcium of LNCaP cells. AB - Mibolerone (dimethylnortestosterone) or 5 alpha-dihydrostestosterone (DHT) increase intracellular calcium (Ca2+i) of human prostate cancer cells (LNCaP) as early as 2 min after treatment. These effects were concentration-dependent (10( 6)-10(-12) M) and they were blocked by preincubation with hydroxyflutamide (10( 6) M). Verapamil (10(-6) M) also suppressed the mibolerone (10(-6) M)-induced increase in Ca2+i, in cells which were previously exposed to 1 mM CaCl2 introduced in a Ca(2+)-free media. The results indicate that androgens elicit changes in Ca2+i in LNCaP cells as a result of Ca2+ influx through L-type channels in the plasma membrane. Since androgens are involved in the regulation of prostate cell division and growth, these findings suggest that calcium is involved in metabolic and mitogenic responses to steroid hormone in target cells. PMID- 1883395 TI - The activation of cAMP-dependent protein kinase is directly linked to the inhibition of osteoblast proliferation (UMR-106) by parathyroid hormone-related protein. AB - The present study was performed to compare the effect of parathyroid hormone related protein (PTHrP) on the proliferation of osteoblastic osteosarcoma cells (UMR-106) with that of PTH and characterize the direct involvement of cAMP in the change of osteoblast proliferation by PTHrP. Human(h)PTHrP-(1-34) (10(-11)-10( 7)M) dose-dependently inhibited [3H]thymidine incorporation (TdR) in the same manner as hPTH-(1-34). The simultaneous addition of PTHrP and PTH at a maximal effective dose of 10(-7) M did not cause additive suppressive effect on cell proliferation. Rp-cAMPs, which has been recently shown to act directly as antagonist in the activation of cAMP-dependent protein kinase (PKA), dose dependently (10(-6)-10(-4)M) antagonized PTHrP-induced suppression of TdR in the same manner as PTH. Present study indicated that PTHrP has the same effect on osteoblast proliferation as PTH and that the activation of PKA is directly linked to the change of osteoblast proliferation by PTHrP. PMID- 1883396 TI - Immunoenzyme determination of total serum ceruloplasmin. Application to Wilson disease. AB - Enzyme immunoassay for ceruloplasmin (CP)*, employing monospecific CP antibodies labeled with horse radish peroxidase was developed. This method permits to determine total content of CP, which is present in Wilson disease patients' blood in enzymatically active and enzymatically inactive forms. The evidence is presented that the method can be used for a direct determination of CP in blood serum. The minimal CP concentration which may be determined by enzyme immunoassay (IEA) is 5.10(-9) g/ml. The method was used for determination of CP concentrations in Wilson disease patients' blood with different disease severity. Analysis of blood samples taken from 6 Wilson disease patients with the use of IEA method revealed similar total CP concentrations. At the same time, the oxidase activities of CP in the blood of different patients varied more than sevenfold. PMID- 1883397 TI - Improved procedure for the purification of hepatic lipase from rat liver homogenate. AB - A procedure is described for the purification of hepatic lipase (HL)4 from rat liver homogenate which results in a high yield (41%) of electrophoretically homogeneous enzyme. The method is based on that of Twu et al. (Biochim. Biophys. Acta 1984: 792, 330), but it is more efficient with respect to yield (about 4 fold) and purity (1.6-fold). It includes the preparation of a high-speed supernatant, chromatography in series on octyl-, heparin- and concanavalin A Sepharose, and finally gel filtration. On SDS-PAGE analysis, the purified enzyme exhibited an apparent molecular mass of 63.6 +/- 3.2 kDa. Heterogeneity was observed, when purified HL was subjected to isoelectric focussing. The enzyme displayed a specific catalytic activity of 23,000 U* (mumol fatty acid released per h at 37 degrees C) per mg protein, when assayed with trioleoyl glycerol suspensions in arabic gum. A highly specific antiserum against rat liver HL, capable of inhibiting 817 mU* HL per microliter antiserum, was raised in rabbits. PMID- 1883398 TI - Fluorescence changes of 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole bound to thiol groups of gizzard myosin. AB - The fluorescence intensity of gizzard myosin that incorporated about 2 mol of 7 chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-C1) at 0.6 M KC1 was quenched at low concentrations of MgATP or in the presence of F-actin. The observed quenching was reduced at high MgATP concentrations. The half maximal change in quenched fluorescence was shifted from 7.5 microM to 25 microM MgATP for NBD-myosin at 0.15 M KC1. The fluorescent label NBD-C1 can be used to detect changes in the conformation of gizzard myosin. PMID- 1883399 TI - Substrate analogues and divalent cations as inhibitors of glutamate decarboxylase from Escherichia coli. AB - To examine the idea that glutamate decarboxylase from E. coli can be a convenient source for the study of the effects of compounds on GABA synthesis in the nervous system, a series of substrate analogues and divalent cations were tested as potential inhibitors of the bacterial enzyme. Those analogues exhibiting inhibitor activity did so in a competitive manner. The most effective inhibitors were 3-mercaptopropionic acid, 4-bromoisophthalic acid and isophthalic acid which exhibited Ki values of 0.13 mM, 0.22 mM and 0.31 mM, respectively. Eight other analogues produced lesser degrees of inhibition. In addition, seven divalent metal cations were tested as inhibitors of the enzyme. However, only Hg2+, Cd2+, Cu2+ and Zn2+ were effective at a concentration of 0.1mM. When these results were compared to the patterns of inhibition of glutamate decarboxylase from mouse brain, certain differences in the manner in which the enzymes responded to the inhibitors, emerged. Consequently, the bacterial decarboxylase may not be a good model for the study of drug action on brain GABA synthesis. PMID- 1883400 TI - Effect of the remaining ischemic liver lobes on DNA synthesis in rat liver regeneration following 70% functional hepatectomy. AB - After 24 h of 70% partial hepatectomy (PH), the activities of thymidylate synthase (TS: EC 2.1.1.45) and thymidine kinase (TK: EC 2.7.1.21) increased by 4.0 and 9.3 times, respectively, compared with their normal levels taken just after PH. In the ligation experiment, where the left lateral and median lobes were ligated as usual PH but were left without resection, regeneration occurs in the non-ligated lobes whose TS and TK levels after 24 h of the ligation were significantly suppressed compared with the PH group. The DNA content of the non ligated lobes was also lower than that of PH group. PMID- 1883401 TI - Effects of vanadate on plasma lipoprotein profiles in experimental diabetic rats. AB - The insulin-like effects of vanadate have been intensively studied in the biological system. Lipids and lipoprotein profiles are altered in diabetes. Rats were made diabetic by a single i.v. injection of streptozotocin (55 mg/kg body weight) in citrate buffer. After the overt of diabetes, the diabetic rats were treated with sodium orthovanadate (0.3 mg/ml) for fifteen days. The altered cholesterol, phospholipids and triglycerides in plasma lipoprotein fractions (HDL, LDL and VLDL) were found to be reverted back to near normal levels in vanadate treated diabetic rats. PMID- 1883402 TI - Sensitivity of brain cholinesterase to cypermethrin toxicity in freshwater teleost Tilapia mossambica. AB - Cypermethrin at sublethal concentrations induced significant changes in acetylcholinesterase (AChE) activity and acetylcholine (ACh) content in the brain tissue of both juvenile and adult-fish. Maximum inhibition of AChE activity is noticed at 6h and 12h after exposure to cypermethrin in juvenile and adult fish respectively. In contrast, the ACh levels registered an elevation in both the cases. During subsequent periods the rate of recovery in AChE activity and ACh content is variable in both the groups. PMID- 1883403 TI - Cypermethrin induced modulations in lipid metabolism of freshwater teleost, Tilapia mossambica. AB - Significant changes in lipid metabolic profiles were observed in brain, liver and gill tissues of T. mossambica under chronic exposure to sublethal concentrations of cypermethrin. Increase in total lipid, lipase and free fatty acids with decrease in glycerol content suggests simultaneous operation of lipogenesis and lipolysis during cypermethrin stress. Phospholipid levels dropped, while cholesterol content increased in all the tissues as a consequence of cypermethrin toxicity. PMID- 1883404 TI - Isolation and characterization of two antigenic glycoproteins from the pollen of Prosopis juliflora. AB - Two antigenically active glycoprotein fractions were isolated from crude extract of the pollen of Prosopis juliflora using DEAE-cellulose ion exchange chromatography. The glycoproteins gave single band on polyacrylamide gel electrophoresis. The molecular weight of these two glycoprotein was 20,000 and 10,000 as determined by gel filtration on Sephadex G-75. With the help of crossed immunoelectrophoresis and gel diffusion crude extract exhibited twelve and three precipitating antigens suggesting its heterogeneous nature; and the purified glycoprotein fractions however formed single precipitin band on gel diffusion test and immunoelectrophoresis. As tested by ELISA the polyclonal antisera raised in rabbit showed strong binding affinity with glycoprotein of MW 20,000. These result indicates that the two glycoprotein fractions are not antigenically identical. PMID- 1883405 TI - Hydrophobic interaction between tryptophan and some synthetic nucleosides. AB - The interaction of 29 synthetic nucleosides with tryptophan was studied by charge transfer reversed-phase thin-layer chromatography and the relative strength of interaction was calculated. In the majority of cases Trp significantly decreased the lipophilicity of the nucleosides. This effect may be due to the interaction between the more hydrophilic Trp and the more lipophilic nucleosides, resulting in charge-transfer complexes of moderate lipophilicity. Stepwise regression analysis proved that the length of the alkyl substituent of nucleosides significantly influences the strength of interaction. Our findings supports the hypothesis that the nucleosides turn toward Trp with their alkyl substituent and the binding is of hydrophobic character. PMID- 1883406 TI - Localization of L-alanine: 4,5-dioxovalerate transaminase in the matrix of the rat kidney mitochondria. AB - The bulk of the enzyme L-alanine: 4,5-dioxovalerate transaminase, which catalyses the transamination reaction between L-alanine and 4,5-dioxovalerate to synthesize delta-aminolevulinic acid was predominantly recovered in the mitochondrial matrix. Sub-fractionation procedure of the mitochondria involved the use of digitonin and lubrol followed by differential centrifugation to separate soluble and particulate enzymes. Lubrol did not inhibit this enzyme. Presence of this enzyme in the mitochondrial matrix was further confirmed by western blot analysis. The results support the conclusion that L-alanine: 4,5-dioxovalerate transaminase is localized and functions in the mitochondrial matrix. PMID- 1883407 TI - A new beginning: current trends in pediatric heart transplantation. AB - Recent experience with heart transplantation in the newborn infant as a surgical option for the treatment of HLHS and other fatal heart abnormalities has encouraged the outgrowth of infant heart transplant programs throughout the world. Current trends include noninvasive evaluation of rejection, minimizing immunosuppressive therapy in this age group, and evaluating societal issues such as the cost of transplantation and parental compliance as an indicator of outcome. Implications for nursing practice involve the support of infants and their families during the evaluation process, thus allowing families to receive appropriate counseling regarding their options. This support may include the obstetric nurse in a small hospital or the nurse practitioner in the neonatal intensive care unit. Heart transplant coordinators facilitate the rapid transfer of information from the transplant center to the referring facility regarding management principles that are necessary to support an infant dying of HLHS. Nursing implications in the psychosocial arena include assessing family compliance in an effort to determine its impact on a successful surgical outcome. After transplantation, nursing practice is challenged by participating in the determination of rejection, and contributing to long-term follow-up care. PMID- 1883408 TI - Treatment of acute hypoxemic respiratory failure caused by chlorine exposure. AB - Chlorine inhalation may rapidly cause pulmonary edema, leading to acute hypoxemic respiratory failure. We report a 12 year old with acute respiratory failure from inhalation injury after he accidentally dropped chlorine tablets into a swimming pool. Supplemental oxygen alone failed to provide adequate arterial oxygenation. We administered positive end expiratory pressure (PEEP) in the emergency department, resulting in markedly improved oxygenation. Early institution of PEEP should be considered in patients with chlorine poisoning when supplemental oxygen alone is insufficient. PMID- 1883409 TI - Acupuncture and postoperative sickness. PMID- 1883410 TI - Using anticoagulants safely. Guidelines for therapeutic and prophylactic regimens. AB - Heparin and warfarin sodium (Coumadin, Panwarfin, Sofarin) are used most often to treat acute and recurrent venous thromboembolic disease, arterial disease, valvular heart disease, and atrial fibrillation. These agents along with dextran, pneumatic compression devices, and gradient stockings are also used to prevent deep venous thrombosis and pulmonary embolism in patients at high risk (eg, those with venous stasis, lower limb or spinal cord trauma, clotting abnormalities). Anticoagulation therapy is monitored by maintaining the activated partial thromboplastin time and the prothrombin time in the therapeutic range. PMID- 1883411 TI - Exclusion of the gene responsible for facioscapulohumeral muscular dystrophy (FSH) at 6q23-q27. AB - Facioscapulohumeral muscular dystrophy (FSH) is an autosomal dominant condition with variable expressivity and age dependent penetrance. Linkage studies still did not exclude regions 11, 2q, 6q, 7p, 8p, 10q, 12p and 14p as possible locations for the FSH gene. In the present study we have analysed 80 individuals (36 patients and 44 normals) belonging to 8 unrelated Brazilian families with 3 probes located on the long arm of chromosome 6:MHB(6q22-q23), ESR(6q24-q27) and TCP1(6q25-q27). Results of linkage analysis suggest that the gene responsible for FSH muscular dystrophy is not in the region 6q23-q27. PMID- 1883412 TI - Intrathecal immunoglobulin synthesis. Comparison of various formulae with the 'gold standard' of isoelectric focusing. AB - The recent introduction of a further new formula for calculating intrathecal Ig synthesis led us to compare the results of calculations obtained when using it and certain other older formulae with those of isoelectric focusing (IEF), since only the latter proves the intrathecal synthesis of oligoclonal proteins. On comparison, it was found that the results produced by the usual formulae were, without exception, inferior to those of isoelectric focusing. By using Receiver Operating Characteristic (ROC) curves, it is shown that calculations with the Reiber formula agree best with IEF. Virtually the same results are obtained with the "ln IgG index + 1" and "IgG index". PMID- 1883413 TI - A battle plan for patients in pain. PMID- 1883414 TI - Bowen's disease and internal cancer. PMID- 1883415 TI - Prolactin stimulates the release of oxytocin in lactating rats: evidence for a physiological role via an action at the neural lobe. AB - The present studies were designed to investigate whether prolactin (PRL) influences the secretion of oxytocin (OT) in lactating rats, and to test whether the previously reported inhibitory and stimulatory effects of dopamine-2 (D-2) agonists and antagonists, respectively, on OT release might be secondary to their respective inhibitory and stimulatory effects on the release of PRL. Intravenous administration of either rat (r) or ovine (o) PRL to lactating, nonsuckled rats increased basal plasma concentrations of OT. rGH was ineffective, but administration of oGH did produce some stimulation of OT release. Both oPRL and rPRL significantly enhanced the electrical stimulation-induced release of OT from isolated stalk-neurointermediate lobes, in vitro, without affecting the basal release of the peptide. oGH was ineffective on basal or stimulated in vitro OT release, and neither hormone altered basal or stimulation-induced release of vasopressin from these tissues. Both rPRL and oPRL reversed the inhibitory effect of the D-2 dopamine agonist bromocriptine. Immunoneutralization of circulating PRL with a highly specific antiserum abolished the increases in OT in response to either suckling or to administration of the D-2 dopamine antagonist domperidone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883416 TI - High serum selenium concentrations in reindeer breeding Lappish men. AB - This study investigated the relationship of serum selenium to its dietary sources in a group of Lappish men and a control population. Lappish men had higher serum selenium concentrations than non-Lappish men (1.79 vs 1.58 mumol/1; p = 0.003). Serum selenium correlated positively with consumption of reindeer meat, age and cholesterol. In linear regression models, however, being Lappish was the most significant predictor of high serum selenium. Lappish men ate more reindeer meat (p = 0.001) and less fish (p = 0.013) than men in the control group. Consumption of reindeer meat was also correlated with higher serum cholesterol levels. We conclude that high serum selenium concentrations in Lappish men may be important since low mortality from cancer is reported in this group. PMID- 1883417 TI - Diabetes prevalence in Alaska, 1984-1986. AB - The prevalence of diabetes in Alaska from 1984 to 1986 was determined through medical records review. Cases were identified from hospital and physician discharge forms and from financial abstracts. As of December 1986, 3,719 Alaskans met the criteria for physician diagnosis of diabetes. The overall age-adjusted prevalence of diagnosed diabetes mellitus, 1,357/100,000, was lower than the U.S. rate of 2,470/100,000. The overall age-adjusted prevalence rates of specific complications and pregnancy among Alaskans with diabetes were retinopathy- 167.5/1,000; blindness--24.3/1,000; amputations--19.4/1,000; end stage renal disease--9.7/1,000; pregnancy--50.7/1,000. Limitations in available data sources such as death certificates, hospital records, and subspecialists' medical records provided serious problems in identifying persons with diabetes, especially those in the 30- to 69-year age group who have not yet developed complications requiring hospitalization or subspecialty care. This population perhaps is most in need of services to prevent future complications of diabetes. PMID- 1883418 TI - Right-branch bundle block in circumpolar Inuit. AB - The prevalence of right-branch bundle block (RBBB) has been examined in the Inuit residents of Igloolik (69 degrees 40'N, Canadian N.W.T.) over a twenty-year period. Original reports of a very high prevalence of RBBB probably reflected a selective testing of patients with chronic respiratory disease by visiting physicians. Cases of RBBB are certainly seen somewhat more frequently than in a southern community, but the majority of subjects show no more than a slight notching of the R wave of the electrocardiogram, with no appreciable broadening of the QRS complex. While a few of the more marked cases of RBBB may be attributable to chronic respiratory disease, the majority are associated with high normal values for both lung function and predicted maximal oxygen intake. The probable cause is thus a ventricular hypertrophy due to the vigorous physical activity demanded by life in a northern community rather than chronic respiratory disease. The physical demands of life in Igloolik have diminished over the past two decades, and an apparent increase in the prevalence of RBBB over this period is probably due mainly to a great awareness+ of the condition by those reading the electrocardiograms. PMID- 1883419 TI - Transcapillar metabolism of lipid- and watersoluble antioxidants as marker of chronical stress in coming population of circumpolar regions. AB - It was shown that the content of the lipid peroxide oxidation products and basic lipid and soluble antioxidant products in capillary and venous blood reflect the tissue trophy provision process in the chronic ecology stress condition. The high reactive oxygen species (ROS) generation in the xanthine-xanthine oxidase system is one of the important mechanisms which is responsible for capillary penetration disturbance and for accelerated development of inflammatory and non-inflammatory disease among immigrants to Circumpolar regions. PMID- 1883420 TI - Personality profiles of Iditarod mushers as compared by finish group. AB - This study uses a personality profile questionnaire to determine what it is about a person's character that makes them unique to their finish place in the Iditarod Trail Sled Dog Race using data collected from 1988 and 1989. It is the purpose of this study to determine differences in personality that make a musher a top ten finisher as opposed to those who finished in other groups. Mushers were divided into five groups: 1) top ten, 2) 11 to 20, 3) 21 to 30, 4) 31 to last, and 5) scratches. Data was subjected to an analysis of variance (ANOVA) and a Pearson Product-Moment Correlation to determine if any significant distinctions occurred among these groups. A main effect is found in Factor E, Factor F, Factor L, and Factor Q2. In Factor E, Group 1 (top ten finishers) was found to be more aggressive. This group is also more enthusiastic (Factor F). Top mushers are more suspicious and hard to fool (whereas those who finish last are more trusting [Factor L]). Top ten finishers are more group-oriented than the rest of the mushers, inferring that they get along with others and are more helping (Factor Q2). These data suggest that to place in the top ten pack of Iditarod mushers, one must be aggressive, enthusiastic, and calculating. PMID- 1883421 TI - Cosmic rays from the sun--health risks now apparent. PMID- 1883422 TI - Disease pattern in Greenland: studies on morbidity in Upernavik 1979-1980 and mortality in Greenland 1968-1985. AB - The disease pattern is described for the population of Upernavik, which is the administrative centre of a very large, sparsely populated municipality in North Western Greenland. The number of medical contacts per person was by and large similar in Upernavik and Denmark despite different health care systems, but the distribution of diagnoses was different. Persons with poor socioeconomic status (housing conditions and social group) were admitted to hospital more often than those with high status. Mortality in Greenland was studied using a computerized register of causes of death covering all deaths in residents of Greenland during 1968-1985. Age standardized mortality rate was twice as high in Inuit of Greenland as in the population of Denmark but five times higher in children. Mortality due to infectious diseases, ischaemic heart disease and certain accidents decreased during the period studied while mortality due to lung cancer, suicide and homicide increased. Regional differences in mortality were pronounced with high infant mortality and high mortality from acute infections and accidents in the socioeconomically poor settlements and remote districts. The suicide and homicide rates were highest in the capital and in the remote East Greenland. Compared with Denmark, mortality rates were higher in Greenland from most causes with ischaemic heart disease as an exception, being significantly less common in Greenland in both males and females. A comprehensive literature review describes the disease pattern in Greenland with special emphasis on the period after 1970. It is concluded that epidemiology can contribute to future health planning in Greenland and that research and development must be given high priority. Some major health problems facing the Greenlandic community are the high mortality from suicides and homicides, the prevalence of violence often triggered by alcohol, the many accidents, the high infant and child mortality and the high mortality from preventable cancers (lung and cervix). PMID- 1883423 TI - Standard-setting plans for the NBME comprehensive Part I and Part II examinations. AB - The National Board of Medical Examiners (NBME) has reviewed its procedure for setting pass-fail standards in conjunction with the introduction of its comprehensive Part I and Part II examinations in 1991. This report gives background information on the procedures used for the past decade to set pass fail standards for the Part I and Part II examinations, an overview of the NBME's research on standard setting, under way since 1987, and a statement of its plans for determining pass-fail standards for these examinations. In 1981 the NBME changed from the norm-referenced standard, used since the 1950s, to a criterion group approach to setting pass-fail standards. Although the criterion-group system resulted in more stable standards, it still meant that the standard moved whenever the performance of the reference group changed. After conducting research, surveying constituencies, and examining alternatives, the NBME has adopted a new standard-setting plan that has the following components: a content based standard-setting procedure; determination of standards by an appropriate group; use of a fixed standard; and periodic review of standards and standard setting procedures. This new process will produce three types of improvements: it will incorporate deliberations informed by a wide range of information, including content review; annual review of examinees' performances and pass-fail results and triennial restudy of the process will add further quality control; and a fixed standard will mean that comparable performances will be required across administrations in order to pass. PMID- 1883424 TI - Faculty practice plans: the organization and characteristics of academic medical practice. AB - The contemporary academic medical center is a complex organization providing medical and other professional health education, biomedical and behavioral research, and a comprehensive range of patient care services. This paper presents data from the Association of American Medical Colleges' 1989 survey of 125 member faculty practice plans. The survey data showed that 62% of the 74 responding plans were units or associations within the medical school corporate structure. Plans were organized along a broad continuum from the autonomous, departmental model with decentralized governance and management to the group model with centralized governance and management. The growth of managed care, increased competition, and a greater reliance by the medical school on clinical practice income as a financing source are causing the practice plan to expand beyond billing of professional fees. The survey data showed that 75% of the practice plans operated satellite centers, and 61% planned to build new ambulatory care facilities in order to expand and improve services to patients. The practice plans also have adapted to changes in third-party reimbursement and are establishing mechanisms to negotiate managed care contracts involving multiple clinical departments to increase referrals and maintain patient shares; 86% of the plans participate in at least one managed-care organization. The role of the practice plan will continue to evolve in response to the needs of the academic medical center for a cooperative and supportive environment in which to conduct its traditional missions of teaching, research, and patient care. PMID- 1883425 TI - Everything I know about health care I learned in the Pentagon in World War II. AB - This is a brief autobiographical account by the chief logistical adviser to the surgeon general of the army of his experiences during World War II, when at peak army hospitals had 600,000 patients in bed on one day and used 40,000 physicians, 100,000 nurses, and 600,000 medical corpsmen to care for them. The recapitulation of that experience calls attention to the fragility of hospital planning, the dangers that underemployed physicians will overtreat patients, the advantages of using nurses as patient care managers in hospitals, and the desirability of not operating too close to the margin. These events of World War II also provide background for understanding the origins of three major post-World War II transformations of U.S. medicine, specifically the much-enhanced demand by the American public for access to a much higher level of medical care than that to which they had earlier been accustomed; the greatly enlarged expenditures of the federal government for basic biomedical research, which derived momentum from the success of research during World War II; and the victory of specialism that captured U.S. medical education and treatment. PMID- 1883426 TI - Phase-in of the NBME comprehensive Part I examination. PMID- 1883427 TI - The inadequacy of recent research on computer-assisted instruction. PMID- 1883428 TI - The threatened role of volunteer faculty members. PMID- 1883429 TI - Student loan programs. PMID- 1883431 TI - Assessment of constituency opinion about NBME examination standards. AB - The National Board of Medical Examiners (NBME) reviewed its procedures for setting pass-fail standards in conjunction with the introduction of its comprehensive Part I and Part II examinations in 1991. A component of the review was the 1990 survey of 12 NBME constituencies to assess opinions about pass-fail rates and standard setting. The survey responses, generally consistent across groups, revealed (1) support for a more even distribution of fail rates across the three examinations, (2) support for a fixed standard, with pass-fail rates that change depending on the performance of a cohort of examinees, and (3) a favorable reaction to setting performance standards based on a review of the examination content. These responses may serve as a resource and a frame of reference for determining the standards for the comprehensive Part I and Part II examinations. PMID- 1883430 TI - Reexamination of relationships between students' undergraduate majors, medical school performances, and career plans at Jefferson Medical College. AB - A reexamination of the possible relationships between medical students' undergraduate academic majors and their medical school performances and career plans seems appropriate, given the continuing changes in the characteristics of the medical school applicant pool in the last several years. This study investigated these relationships by comparing cognitive and noncognitive characteristics of medical students who had had different undergraduate majors. The study sample consisted of 812 students who entered Jefferson Medical College between 1985 and 1988. They were classified into six categories based on their undergraduate majors: biological, chemical and physical, social and behavioral, other sciences, humanities and arts, and indeterminate majors. Results indicated that performances in the basic science component of medical education were about the same for students with different undergraduate majors. The groups had similar rates of delayed graduation, but the attrition rate was highest for students who had majored in humanities and arts. The students in undergraduate disciplines traditionally oriented toward medicine (biological, physical, and chemical sciences) were younger and had made the decision to become a physician at earlier ages than had their counterparts with undergraduate majors in social sciences and humanities. Also, the groups differed with regard to their estimates of their future incomes and plans for professional activities after graduation. Similarities concerning the students' preferred professional activities were also noticed among the groups. PMID- 1883432 TI - Predictive validity of a house-officer selection process at one medical school. AB - This study explored the rank list generated by a process of evaluating applicants for a surgery residency; the process is a revision of an older process (pre-1982) used for that purpose. The study's aim was to learn whether the new process is more predictive of residents' performances in their first year than was the process it replaced and whether the rough rankings computed directly from ratings of applicants are more predictive than the final rankings determined in a meeting by the department faculty, who modify the rough rankings. The 1982-1986 rankings and performances of 32 first-year residents at the University of North Carolina at Chapel Hill School of Medicine were studied and compared with the rankings and performances of 77 applicants from 1976 and 1978-1979 under the previous system. Correlation analyses revealed that for the applicants studied, the rough rankings in the new and the previous systems were equally predictive of performances as measured by rating scales, but that the new system was more predictive of performances on the surgery in-training examination. However, all correlations were small. Finally, the rough rankings obtained under the new system were more predictive of the residents' later performances than were the faculty's final rankings. PMID- 1883434 TI - Gender bias of Ohio physicians in the evaluation of the personal statements of residency applicants. AB - Sexism has been documented at every level of medical training as well as in the community of practicing physicians. Although there is speculation in the literature about sexist attitudes and perceived sexual discrimination influencing a medical student's choice of specialty, there are few data on gender bias in the evaluation of residency candidates applying in different specialties. In 1989, the authors created six personal statements of interest in a residency, each from a different type of fictitious residency candidate (three men, three women, at three levels of medical school achievement) and mailed one or another of the statements, chosen at random, to the 2,478 board-certified Ohio physicians practicing in six specialties in which U.S. women in residencies were underrepresented (less than 12%) compared with the percentage of women in medical schools, and to the 3,586 board-certified Ohio physicians in another six specialties in which women in residencies were overrepresented (more than 38%). The physicians consistently rated the women candidates more favorably than they did the men candidates. PMID- 1883433 TI - Medical school and residency performances of students admitted with and without an admission interview. AB - In 1982 the Brown University Program in Medicine eliminated the personal interview from its process of selecting applicants for admission to medical school. This study compares the 113 M.D.-program students admitted to the first three classes (entering between 1983 and 1985) without an interview with the 67 students in the previous three classes admitted with an interview. The students' characteristics were essentially the same with respect to the preadmission variables, the proportions of women and minority students, course performances, scores on Parts I and II of the National Board of Medical Examiners examinations, and evaluation scores from residency program directors. This study offers additional evidence that the selection interview, as practiced in most U.S. medical schools, does not contribute to the predictive validity of the admission process. PMID- 1883435 TI - Positive effects of a clinical performance assessment program. AB - Since 1986, there has been a clinical performance assessment program for fourth year students at the University of Massachusetts Medical School. Students interact with several standardized patients (SPs) and complete other tasks such as interpretation of electrocardiograms and interpretation of X-rays. Scores are generated both by checklists and rating forms completed by the SPs and by paperwork completed by the students at the end of each encounter. Since 1986, students have been asked how frequently they have been observed by faculty and residents as they interacted with actual patients; the students report that such observations have markedly increased. Since 1989, there has been increased feedback to students by the attending faculty during and following clinical rotations. Although it is difficult to claim cause and effect, it is clear that since the inception of this exercise, the faculty have made a conscious effort to improve students' clinical skills by providing increased observation and feedback. PMID- 1883436 TI - Gender, family status, and career patterns of graduates of the University of Calgary Faculty of Medicine. AB - In 1986 the authors sent a questionnaire to 745 physicians who had graduated between 1973 and 1985 from The University of Calgary Faculty of Medicine. The survey obtained information on the graduates' status as parents, the "breaks" they had taken from their practices, and the hours per week they devoted to direct patient care, in order to observe what relationship the graduates' gender and status as parents had on the other variables. The women were far more likely to have taken breaks for parental leave, but the differences in the frequencies of breaks taken by the men and the women for other reasons were less striking. The women were working fewer hours in direct patient-care settings, and those women who were parents and under 35 years old spent fewer hours on patient care than did the men (from all age groups) who were parents. The authors discuss their findings in terms of the impacts of age and cohort effects and the possible lessening of gender-based differences in present-day physicians' practices. PMID- 1883437 TI - A performance-based method for early identification of medical students at risk of developing academic problems. AB - The authors studied three classes at the Albert Einstein College of Medicine and found that students' performances on examinations administered during the third month (November) of medical school were highly predictive of their subsequent performances during the first two years of medical school. The investigation had two components: (1) a retrospective study of the classes of 1988 and 1989, which found that students' November grades from three first-year courses predicted 76% of the variance in the year-one weighted aggregate score and 41% for the year-two score, and (2) a prospective study of the class of 1992, in which three November of year one examination scores of the students in the lowest quarter of the class were highly predictive of their encountering substantial academic problems, with a sensitivity of .77 and a specificity of .99. This performance-based method was found to be more powerful than using the scores on the 1977 version of the Medical College Admission Test or the students' undergraduate grade-point averages, or both, in identifying individual students who were academically at risk. PMID- 1883438 TI - Opinions about management of geriatric syndromes given by internal medicine residents in two programs. AB - Internal medicine residents in two programs providing different amounts of training in geriatrics were surveyed in 1988 regarding their opinions about the management of four geriatric problems and two traditional internal medicine problems. The residents generally agreed that geriatric problems were legitimate concerns in a general internal medicine practice but demonstrated less confidence in the management of geriatric problems than in the management of traditional problems. Residents from the program that provided more extensive training in geriatrics evidenced greater support for nondiscriminatory care of elderly diabetics; otherwise there was no convincing evidence of differences between the two programs. The authors conclude that educational efforts in geriatrics need to target trainees' confidence in the management of geriatric problems. PMID- 1883439 TI - Investigating whether education of residents in a group practice increases the length of the outpatient visit. AB - This prospective study, carried out over an eight-week period in 1990, compared the amount of time required for 468 outpatients in an academic group practice (pediatric orthopedics) to be evaluated by an attending surgeon working with a resident with the time required for 216 patients in the same practice to be evaluated by the attending surgeon only. On the average, 24.2 minutes were added when a resident was involved: 12.6 of these for the resident's examination of the patient and the remaining 11.6 for the resident's discussion of the case with the attending surgeon. These findings suggest that the education process builds in a time cost not only for the patient but for the attending surgeon, who has less time to see additional outpatients than does a private practitioner or a physician in a health maintenance organization. PMID- 1883440 TI - Perceptions of residents and program directors at Case Western Reserve on issues associated with limitations on residents' hours. PMID- 1883441 TI - The effects of education indebtedness on career plans of graduates of a private medical school. PMID- 1883442 TI - Participation of nurses in the evaluation of residents' interpersonal skills. PMID- 1883443 TI - Sources of encouragement or discouragement to students as they decided whether to enter medical school. PMID- 1883444 TI - Training health care professionals to communicate with patients with mental retardation. PMID- 1883445 TI - Status report on ambulatory care and education in the VA Western Region and western medical schools. AB - Since the initial 1988 Ambulatory Care and Education (ACE) conference, reported in the October 1989 supplement to Academic Medicine, the Western Region Veterans Health Administration and its 11 affiliated western medical schools have established several programs and related activities that implement strategic ACE recommendations. This report gives an update on the ACE Advisory Group; the Pilot Ambulatory Care and Education (PACE) Center at the VA Medical Center, Sepulveda, California; other innovative ambulatory care and education projects; the second ACE Development Conference; and future activities in the expanded Western Region of the Department of Veterans Affairs. PMID- 1883446 TI - Development and evaluation of a required ambulatory medicine clerkship. PMID- 1883447 TI - A landmark document in the growing body of literature about AIDS. PMID- 1883448 TI - The crucial link between laboratory animal research and human health. PMID- 1883449 TI - Medicine, law, and humanities. PMID- 1883450 TI - Abrahamson's disease. PMID- 1883451 TI - Blaming the Boards: are we lapsing into educational luddism? PMID- 1883452 TI - National curricular guidelines for third-year family medicine clerkships. The Society of Teachers of Family Medicine (STFM) Working Committee to Develop Curricular Guidelines for a Third-Year Family Medicine Clerkship. AB - In most U.S. medical schools, required clerkships in internal medicine, pediatrics, surgery, obstetrics and gynecology, and psychiatry are considered the core components of a student's clinical education. Because the specialty of family practice is not as well established in the medical school curriculum, the federal government is interested in promoting the specialty as part of its continuing efforts to increase the number of primary care physicians. Therefore, in August 1989 the Division of Medicine, Bureau of Health Professions, United States Department of Health and Human Services, awarded a purchase order to the Society of Teachers of Family Medicine to develop curricular guidelines for third year family medicine clerkships. The authors represent the working committee that developed these guidelines. This paper describes the process used to develop the core curricular guidelines, presents the product of the curriculum development activities, and discusses dissemination, implementation, and further development activities. PMID- 1883453 TI - The geographic relationships between physicians' residency sites and the locations of their first practices. AB - The uneven geographic distribution of physicians has been identified as a significant problem for the delivery of health care services. The present study examined one of the factors that contribute to the distribution of physicians; how far they move from their residency sites to establish their first practices. In 1989, the authors selected a random sample of 701 U.S. residency programs in the ten specialties with the most practitioners, and measured the distance each of these physicians moved to his or her first practice location. Of the 701 programs, 58.5% provided usable information about 2,612 physicians. Of these physicians, over 40% had moved less than 10 miles from their residencies, and over 50% had moved less than 75 miles. Comparisons among the physicians from the various specialties showed that the primary care physicians moved significantly shorter distances than did those from the other specialties. In the last two decades, many efforts have been made to increase the geographic distribution of physicians. The evidence from this study suggests that so far as the distances that physicians move from their practice sites are concerned, little has changed. Recent graduates of residency programs show no more tendency to move far from their residency sites than did their counterparts 30 years ago, as reported in the literature. PMID- 1883454 TI - Validity and generalizability of global ratings in an objective structured clinical examination. AB - The performance of foreign medical graduates on multistation standardized patient based tests and used to determine the validity and generalizability of global ratings of their clinical competence made by expert examiners. Data were derived from the entrance examinations of the 1989 and 1990 applicants to the Ontario Pre Internship Program and the exit examination of 24 participants from the 1989 cohort. For each candidate, the examiners completed a detailed checklist and two five-point global ratings dealing with the candidate's approach to the patients' problem and attitude toward the patient. Generalizability coefficients for both ratings were satisfactory and stable across cohorts. Construct validity of the global ratings was demonstrated by comparing entry and exit ratings and by evidence of significant and positive correlations between the global ratings and total test scores. Tentative evidence of criterion validity of the global ratings was demonstrated. These findings suggest that global ratings by expert examiners can be used as an effective form of assessment in multistation standardized patient examinations. PMID- 1883455 TI - Comparison of faculty members' and students' perceptions concerning performance criteria and evaluation strategies at the University of New Mexico School of Medicine. AB - Faculty members' and students' perceptions concerning the relative importances of (1) various performance criteria for students and (2) strategies of evaluation were determined in 1989 by a questionnaire in a single medical school that had both a problem-based, student-centered curriculum and an organ-block curriculum (i.e., regular track). The greatest differences in the rankings of both areas were found between those given by the freshman and sophomore students in the problem-based curriculum and those given by the same groups in the regular track. The faculty members' perceptions tended to be closer to those of the students in the regular track. PMID- 1883456 TI - Interest in geriatrics education among family practitioners and internists in Virginia. AB - To determine primary care physicians' interest in continuing medical education (CME) in geriatrics, the authors surveyed all Virginia family practice (FP) physicians and internal medicine (IM) physicians, a total of 1,882. Sixty-one percent (1,139) responded, of which 56% were FP physicians and 44% were in IM. On a visual analog scale to measure the physicians' interest in geriatrics education (from 1 = unimportant to 10 = very important), the FP physicians' mean score was 6.4; the IM physicians' mean score was 6.1. The preferred form of education was a two-to-three-day conference, and the preferred topics were acute care, long-term care, and rehabilitation. Stepwise multiple regression showed that the physicians' intent to take the Added Qualifications in Geriatric Medicine examination was the major predictor of their interest in geriatrics education (R2 = .12, p = .0001). Also significant contributors were the total amount of geriatric care the physicians provided, the home visits they provided, their prior participation in geriatrics CME conferences, absence of a negative attitude toward the Medicare system, and their lack of confidence in their current knowledge of geriatrics. The final model could account for 20% of these physicians' interest in future CME in geriatrics (R2 = .20). These findings may help geriatrics educators develop methods to educate primary care providers about geriatrics. PMID- 1883457 TI - Development of a basic test of geriatric medicine. PMID- 1883458 TI - Similarities in the personalities of women and men who were first-year medical students planning careers as surgeons. PMID- 1883459 TI - Using standardized patients to improve medical students' interpersonal skills at the beginning of their third year. PMID- 1883461 TI - Comparing examination scores and personality types of students from three classes. PMID- 1883460 TI - Faculty members' ratings of the importances and the discriminating powers of nine aspects of students' clerkship performances. PMID- 1883462 TI - Financing medical education, 1989-90. PMID- 1883463 TI - The long-term traffic safety impact of a pilot alcohol abuse treatment as an alternative to license suspensions. AB - During the 4-year period following a repeat driving under the influence (DUI) conviction, participants in 12-month treatment programs had worse overall traffic safety records than did recipients of license suspensions. The results from a series of analyses using repeated measures analysis of covariance showed that, in comparison with license-suspension recipients: (i) participants had significantly higher rates (70%) of nonalcohol-related accidents and convictions, (ii) participants had a significantly lower rate (9%) of alcohol-related convictions, but no difference was found on alcohol-related accidents, and (iii) participants had a significantly higher rate (30%) of total accidents (p less than .05). These results suggest that the use of license-suspension waiver as an incentive to participate in a drinking driver program had a negative impact on traffic safety. The predicted reductions in alcohol-related accidents among program participants did not occur, and reductions in nonalcohol-related accidents, which could have been achieved with license suspensions, were sacrificed. It was recommended that some other alternative besides license-suspension waivers be used as an inducement for repeat DUI offenders to participate in treatment. PMID- 1883464 TI - The visual and driving performance of monocular and binocular heavy-duty truck drivers. AB - This study compared the performance of 40 monocular and 40 binocular tractor trailer drivers on measures of both visual and driving performance. On the visual measures, the mononuclear drivers were significantly deficient in contrast sensitivity, visual acuity under low illumination and glare, and binocular depth perception. They were not significantly deficient in static or dynamic visual acuity, visual field of individual eyes, or glare recovery. Driving measures of visual search, lane keeping, clearance judgment, gap judgment, hazard detection, and information recognition showed no differences between monocular and binocular drivers. Monocular drives were poorer than binocular drivers only in sign reading distance in both daytime and nighttime driving. This decrement correlated significantly with the binocular depth perception measure. There were large individual differences within each group for most of the visual and driving performance measures. It was concluded that monocular drivers have some significant reductions in selected visual capabilities and in certain driving functions dependent on these abilities, compared with binocular drivers. However, monocular drivers are not significantly worse than binocular drivers in the safety of most day-to-day driving functions. Implications of these findings and the large individual differences within each group are discussed. PMID- 1883465 TI - Analysis of the frequency and duration of freeway accidents in Seattle. AB - Accidents occurring on congested urban freeways can have enormous impacts in terms of lost commuter time. This paper presents an appropriate statistical analysis of urban freeway accident frequency and duration and discusses how this analysis can be used to guide management strategies that seek to reduce the traffic-related impacts of accidents. The findings and demonstration of analysis procedures should be of considerable value to ongoing and future studies in this area. PMID- 1883466 TI - Impact-induced car fires--a comprehensive investigation. AB - Impact-induced car fires still attract much attention, in spite of a reduction in the rate of their occurrence in recent years. This investigation addresses several issues concerning car fire rates as a function of model year and calendar year, and the sensitivity of these rates to car impact type, impact severity, and car size. Car fuel leak occurrence rates are examined in parallel. The resolution of these issues is based on a comprehensive examination of the voluminous car accident records complied for research purposes by the National Highway Traffic Safety Administration in the past ten years. The findings show a fire rate reduction, as model years progress from the early 1970s to the mid-1980s. A significant part of this reduction takes place across model year 1976, consistent with expectations based on Federal Motor Vehicle Safety Standard No. 301 (FMVSS 301), concerning car fuel system integrity, that became essentially effective in model year 1976. However, substantial reductions of fire rates and fuel leak occurrence rates are evident as model years progress well beyond 1976. Fire and fuel-leak rates are very sensitive to impact type and impact severity; however, rate reductions are evident irrespective of impact type and impact severity. Contrary to a widely entertained notion, fire and fuel-leak rates are found to be rather insensitive to car size. PMID- 1883467 TI - Quasi-induced exposure revisited. AB - Considerable attention is still given to developing and using alternate methods for determining exposure for calculating highway accident rates. A quasi-induced method of measuring exposure developed in the late 1960s is reexamined and found to be promising for determining relative accident involvement rates. A new empirical investigation is offered as the first step in verifying that the characteristics of the "innocent victim" in two-vehicle highway accidents represent a random sample of the driver-vehicle combinations present on the highway system under specified conditions. Quasi-induced exposure estimates are shown to be, at a minimum, consistent and reproducible. PMID- 1883468 TI - Fatal accident involvement rates by driver age for large trucks. AB - Survey data on large trucks involved in fatal accidents and on the travel of large trucks provide estimates of fatal accident involvement rates by driver age. The analysis is focused on the implications of lowering the minimum age for drivers of commercial trucks operating interstate from 21 to 19 years. Fatal accident involvement rates for drivers of large trucks are found to increase with decreasing driver age. The younger drivers are over-involved until about age 27. Drivers under the age of 21 are over-involved by a factor of 6 in comparison to the overall rate for all drivers. Other factors known to have significant influences on the probability of involvement in a fatal accident were examined to determine their association with the over-involvement of younger drivers. The general pattern of over-involvement for younger drivers pervades virtually every combination of factors examined. Thus, it is concluded that the basic trend with driver age shown in the aggregate data is primarily associated with age and is not associated with the other factors examined. The results of this analysis substantiate an elevated risk of fatal accident involvement for younger drivers of large trucks. PMID- 1883469 TI - Assessing driver status: a demonstration experiment on the road. AB - Twenty subjects completed an on-the-road experiment that consisted of two parts on two separate days. One was a one-hour driving test under the influence of alcohol (BAC less than = 0.05%), the second a two-and-a-half-hour driving test under vigilance conditions. Impairment of driving performance was measured in a car-following test as well as in a standard driving test. Changes in relevant physiological parameters, such as ECG and EEG, reflected changes in driver status and predicted driving performance impairment. PMID- 1883470 TI - The effects of mobile telephoning on driving performance. AB - The effects of telephoning while driving were studied in three different traffic conditions, i.e. in light traffic on a quiet motorway, in heavy traffic on a four lane ring-road, and in city traffic. Twelve subjects, unfamiliar with mobile telephones, drove an instrumented vehicle for one hour each day during three weeks and while in each of the three traffic conditions, had to operate the mobile telephone for a short while. To ensure a fixed "heavy traffic load" in the second condition, the subjects were instructed to follow another instrumented vehicle (at a safe distance). The results showed a significant effect of telephoning while driving as opposed to normal driving (i.e., not involving telephone conversation), on the effort subjectively measured by an effort scale and objectively measured by heartrate indices and on some of the measured parameters of driving performance. One half of the subjects had to operate the telephone manually, the other half performed the telephone task with a handsfree mobile telephone set. The subjects who operated the handsfree telephone showed better control over the test vehicle than the subjects who operated the handheld telephone, as measured by the steering wheel movements. Also, a clear improvement over time in the course of the 15 test days was found for some of the measurements. As a consequence of the results, some advice concerning mobile telephoning can be given to authorities, manufacturers, and users. PMID- 1883471 TI - A comparison of diagnostic related group length of stay outliers: motor vehicle crash versus penetrating injuries. AB - The incidence and degree to which patients injured by motor vehicle crashes (MVCs) and penetrating wounds remain in the hospital beyond the diagnostic related group (DRG) mean length of stay (LOS) are compared. During a 12-month period, records for consecutive patients admitted to eight hospitals (including three trauma centers) were studied. Patients aged 13 or younger, staying less than 48 hours, or with major burns or only distal fractures were excluded. In that time, 2,914 patients were eligible. Twenty percent of injuries were penetrating; 27% were MVC injuries; and, 53% were blunt injuries from other causes. Patients injured in MVCs and with penetrating injuries were compared with respect to mean LOS, incidence of DRG outliers, number of hospital days beyond the DRG mean LOS, and demographic variables. Patients injured in MVCs had a greater proportion of DRG LOS outliers and higher mean numbers of DRG excess days than did patients with penetrating wounds (p less than 0.01, for both). Injuries were distributed among relatively more DRGs for MVC patients. The DRG scheme may lack sufficient attention to factors more likely to affect MVC patients, such as multiplicity of injuries, incidence of CNS injuries, ICU requirements, and older age. In structuring more appropriate reimbursement for trauma care, special attention must be paid to patients injured in MVCs. PMID- 1883472 TI - A system for measuring the severity of temporary and permanent disability after injury. AB - 500 patients have been questioned about activities of daily living and mobility 4 and 26 weeks after injury in order to assess the extent of temporary and permanent disability following minor and major trauma. Only those who sustained single injuries have been assessed, resulting in a relatively small number of serious injuries in the sample. In other respects, the population is representative of the daytime attendance at a busy emergency department. Most patients sustained injuries with an Abbreviated Injury Scale (AIS) of 1 or 2 (96%); it is clear that the AIS is unable to distinguish between most small injuries. Assessment was by interview. Although subjective, this has produced results that have face validity and discriminate between a wide variety of injuries. The methodology may be useful in the development of a "disability score," but much more data will be required before this can be achieved. PMID- 1883473 TI - Effects on driving performance of visual field defects: a driving simulator study. AB - To elucidate the possible traffic safety risks induced by visual field defects, a method was developed based on a driving simulator. The capacity to detect stimuli of different sizes appearing in 24 different positions on the screen in front of the driver was measured. Two groups of normal subjects and a number of subjects with different visual field defects were studied. In the groups of normals, the median reaction times were fairly homogenous. There was a slight difference between central and peripheral stimuli, which was somewhat larger for the older subjects. Among the subjects with field defects, the individual variations were very dominant. Very few of these showed a capacity to compensate for their deficiency. In order to gain insight into possible compensatory mechanisms of these persons, eye movement recordings were made. The results indicate that the visual search pattern may be of importance in this respect. Some comparisons with respect to detection capacity were also made with one-eyed subjects and with optically generated field restrictions (spectacles and spectacle frames). PMID- 1883474 TI - [Chlorine coatings on skin surfaces. II. Parameters influencing the coating strength]. AB - Although active chlorine compounds have been used for more than 140 years (Semmelweis, 1848) as a skin disinfectant the phenomenon of the "chlorine covers" not earlier than 1988 has been described for the first time (Hyg. + Med. 13 (1988) 157). It deals with a chemical alteration of the uppermost skin layer which comes apparent in an oxydizing action against aqueous iodide. Its origin is chlorine covalently bound in the form of N-Cl functions to the protein matrix of the horny skin. Since the chlorine covers exhibit a persistant disinfecting activity which might be important for practice, the factors influencing their strength have been established. The most important are: the kind of the chlorine system, the concentration (oxydation capacity), pH, temperature and the volume of the used solution, the time of action, the application technique and the state of the skin. Variations of the latter can be observed at different skin areas of one and the same person as well as at the same areas of different persons, and result in differences of the cover strength up to 100%. The stability on dry skin is very good, showing a decomposition rate of approximately 1.2% per hour. However on skin surfaces moistened by sweat (e.g. hands covered by surgeons gloves) the chlorine cover is disingrated much more faster (decomposition rate: 40-50% per hour). Washing with soap as well as the action of alcohols cause virtually no decrease in the cover strength, while wetting by solutions of reducing agents (e.g. thiosulfate, cysteine, iodide) provokes a fast decomposition suitable for removing the chlorine covers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883476 TI - [Survival ability of genetically engineered strains of Escherichia coli. 1. Physiological characterization and the effect of different physiochemical conditions]. AB - Two genetically engineered E. coli strains L+ and CAG+ possessing the ability to produce the enzyme Pro-urokinase and showing additionally ampicillin resistance, and wild-strains L- and CAG-, were characterized using 328 physiological tests. Their test profiles were compared with those of 30 clinical and nonclinical E. coli isolates. This biotyping made a differentiation and recognition of the genetically manipulated strains possible. It also allowed distinguishing them from the other tested isolates. The genetically engineered strains showed a narrower activity spectrum compared with their wild-strains. However, based on differentiating characteristics, all strains could be clearly biochemically identified as E. coli. Under different laboratory test conditions (organic load, pH, salt content, temperature), the E. coli strains showed no striking features or peculiarities with respect to their survival compared to data from literature. However, low pH (pH less than 5), high salt content (greater than 7%) as well as low (less than 8 degrees C) and high (greater than 37 degrees C) incubation temperatures clearly reduced their ability to survive. Apart from a few exceptions (e.g. survival of strain L+ at 44 degrees C and pH 7 with high cell densities), the survival of the genetically engineered strains corresponded to that of the control and wild-strains. Both CAG strains, especially the genetically manipulated strain CAG+, showed in many cases reduced viability compared with the other strains. PMID- 1883475 TI - [Comparative studies of fresh and seawater for the determination of total coliform and fecal coliform bacteria according to the European Economic Community guideline 76/160 (bathing water) by the use of the most-probable-number method with BRILA-MUG broth and differentiation according to the drinking water ordinance]. AB - During the summer season of 1989 about 222 samples of bathing water (Northsea, Baltic Sea and inland waters) were investigated, i.e. 2 times 1998 dilution tubes (1501 positive) were tested. Results with BRILA-MUG and lactose-bouillon were compared and additional 97 samples were tested with one respectively three colonies by confirmative tests. -- The BRILA-MUG one-tube-test (gas, fluorescence and indol) has as expected larger numbers of total coliforms (GC) and faecal coliforms (FC) in comparison with corresponding numbers for E. coli and coliform bacteria according to German law for drinking water (TrinkwV). -- BRILA-MUG and lactose-bouillon with the same identification mode according to "TrinkwV" has corresponding results concerning E. coli and coliform bacteria. -- Following the identification mode according to "TrinkwV" the total coliforms (GC/gas in BRILA MUG) depending on the origin proved 60-80% as coliform bacteria. Additional API tests showed that the other bacteria are coliform bacteria too or bacteria which can be considered as indicators for water pollution. -- Faecal coliforms (FC/fluorescence and indol-positive) depending on the origin proved 70-90% as E. coli, if following the identification mode according to "TrinkwV". Using 3 instead of 1 colony per positive dilution tube for identification the positive results increased approximately by 9%. 15% of negative results with the identification mode according to "TrinkwV" proved as E. coli-positive with identification according to API-system, i.e. the corresponding rate of E. coli positive tubes will therefore be higher than shown above. The BRILA-MUG one-tube test in connection with the MPN-method can be used successfully to determine the number of total and faecal coliforms according to the EEC-directive for bathing waters. The test needs only a minimum of material and also a minimum of laboratory staff. Differences between this test and other more extensive tests with several biochemical identification steps are negligible. The work load for bathing water tests would not be justified in this case. PMID- 1883477 TI - Exposure to inorganic bromides from greenhouse crops where methyl bromide was applied for soil fumigation. AB - The Authors determined the concentration of inorganic bromides in soil and tomatoes from greenhouses where soil fumigation had been performed using methyl bromide (greenhouse B) and alternative pest control systems (greenhouse A and greenhouse B) before planting. The results obtained demonstrate that concentration of inorganic bromides in foodstuffs should be considered as a marker of exposure to methyl bromide poisoning risk. PMID- 1883478 TI - Cancer mortality from 1978 to 1987 in smaller regions of Styria, Austria, with different environmental conditions. AB - In 1984 we have shown in a study, that regions with high air pollution have a higher respiratory cancer rate than regions without substantial air pollution. In this study 45 small regions of Styria, which can be considered homogenous from an environmental viewpoint, have been studied with respect to age standardized respiratory cancer mortality. These small regions have been classified into regions without substantial air pollution, with substantial air and substantial water pollution. Between 1978 and 1987 we have found that small regions with substantial air or water pollution show an increased age standardized respiratory cancer mortality than small regions with "good" environmental conditions. In some regions the rate was twice as high compared to regions without substantial environmental problems. The main difference was found for the age group between 60 and 75 years. Generally between 1978 and 1987 no trend has been observed, only within age groups a shift can be seen. PMID- 1883479 TI - Anti-acetylcholine receptor antibodies in neonatal myasthenia gravis: heterogeneity and pathogenic significance. AB - Precipitating, blocking and modulating anti-AChR antibodies and their capacity to recognize embryo or adult muscle were investigated in parallel in maternal and neonatal sera of fifty-two newborns and their myasthenic mothers. Twenty-four babies presented neonatal myasthenia gravis (NMG) with a common expression in twenty cases and foetal involvement in four cases. Occurrence of NMG was clearly related to levels of maternal precipitating, decamethonium blocking (DC blocking) and modulating antibodies (respectively P less than 0.001, P less than 0.02, P less than 0.01, Mann-Whitney test), these three parameters being interrelated. The only significant difference between mothers with severely affected babies and others with mild NMG newborns concerned DC blocking antibodies. Transfer fraction of DC blocking antibodies was significantly higher in NMG than in asymptomatic babies. Our data suggest that (1) the amount of anti-AChR antibodies, whatever the tested category, is involved in the pathogeny of NMG in a more direct manner than in adult MG where the correlation with their levels is poor, and (2) among antibodies, those with blocking effects could be preponderant for triggering NMG and be involved in the severity of the disease in the child. PMID- 1883480 TI - Anti-acetylcholine receptor antibodies decrease after thymectomy in patients with myasthenia gravis. Clinical correlations. AB - Clinical course and changes in serum levels of antibodies to the acetylcholine receptor (a-AChR) were followed in 82 patients with myasthenia gravis during a period of 1-8 years after thymectomy. Decrease in a-AChR immediately after thymectomy was influenced by changes in a total IgG. Immunosuppressive medication affected serum a-AChR at all points of time. In a subgroup of 41 patients without thymoma who had no immunosuppressive drugs, there was a steady decrease in a-AChR concomitant with clinical improvement from 6 weeks after thymectomy. PMID- 1883481 TI - Production of interleukin-1 beta-like factor with synovial cell growth promoting activity from adult T-cell leukemia cells. AB - We observed a case of adult T-cell leukemia (ATL) with proliferative synovitis. Culture supernatants from ATL cells (ATL-SN) obtained from the peripheral blood constitutively produced an interleukin-1 (IL-1)-like factor in vitro, as shown by the growth inhibition factor (GIF) assay using the A375 melanoma cell line and the lymphocyte activating factor (LAF) assay using C3H/HeJ thymocytes. Neutralization studies indicated that polyclonal antibodies against IL-1 beta blocked most (80%) of the activity in ATL-SN. In addition, increased amounts of IL-1 beta mRNA were found in the ATL cells by dot blot analysis. Sephacryl S-200 chromatography showed that the molecular weight of this factor was approximately 17.5 kDa, and Western blot analysis revealed that this factor reacted with polyclonal anti-IL-1 beta antibody under the reduced condition. The isoelectric point was 7.5. Furthermore, ATL-SN showed significant activity in promoting the growth of synovial cells in parallel with IL-1 activity. These data suggest that the constitutive production of this IL-1 beta-like factor might be responsible for proliferative synovitis in this case. PMID- 1883482 TI - Comparison of natural antibodies to autoantibodies arising during lupus in (NZB x NZW)F1 mice. AB - Autoantibodies arising in (NZB x NZW)F1 (B/W) mice during the lupus-like syndrome were studied and compared to natural antibodies present in normal mice. The antibody activities were tested in sera, circulating immune complexes (CIC) and kidney eluates, using an enzyme immunoassay against a panel of self and non-self antigens: actin, myosin, tubulin, DNA, myoglobin, spectrin and trinitrophenylated bovine serum albumin (TNP/BSA). In the B/M mouse sera, IgM antibodies reacting with all the panel of antigens (PAg) and comparable to those of normal mice, increased moderately from 5 to 9 months and markedly during the last stage preceding death (10 months), when particularly high levels of anti-DNA, anti tubulin and anti-myoglobin antibodies were noted. Polyreactive IgM antibodies present in CIC were moderately increased while those present in complexes deposited in kidneys were strongly enhanced after the 8th month. IgG antibodies showed an early increase (2 months) in B/W sera for anti-TNP activity, which remained more or less constant until death, while a later (5-6 months) and greater increase of activity, mainly directed against DNA but also against the other antigens of the panel, was observed. In CIC, IgG, mainly anti-DNA but also anti-TNP, were enhanced at the end of the disease while at the same time IgG reacting with all the PAg were found in kidney deposits. Isolation of antibodies from sera on a DNA-immunoadsorbent demonstrated that eluted IgM reacted with all the PAg but mainly with DNA, while IgG reactivity was more restricted to DNA and to a lesser degree to TNP. The D23 idiotype, characteristics of natural polyspecific antibodies, was expressed on IgM and IgG autoantibodies from B/W mice and was enhanced, particularly in kidneys, at the end of the disease. These results demonstrate that natural antibodies are a part of the population of increased autoantibodies in this disease and could participate with IgG anti-DNA antibodies in lupus. PMID- 1883483 TI - Selective abnormalities in the thymic microenvironment associated with avian scleroderma, an inherited fibrotic disease of L200 chickens. AB - As a prelude to deciphering the mechanisms of intrathymic T-cell maturation we produced a panel of 18 monoclonal antibodies (mAbs) against chicken thymic stromal elements. Eleven of these detected epithelial cells. They were: pan epithelial; subcapsule and peri-vascular (pan type 1 epithelium); subcapsular, perivascular and medulla; medulla; or cortex. Of particular interest were the sub specificities within these regions, especially the subcapsular region. Four mAbs stained both epithelial and non-epithelial cells in discrete regions. In addition, three mAbs recognized only non-epithelial cells. One identified macrophages scattered throughout the thymus, another the connective tissue and another the medullary vascular endothelium. These reagents have provided an extensive profile of the thymic stromal architecture and revealed that these cells are equally as complex as the T cells whose differentiation they induce and regulate. While the mAbs provide a valuable means for studying the mechanisms of normal thymopoiesis, their clinical significance is unknown. UCD line 200 chickens develop an autoimmune disease manifest by dermal and internal organ fibrosis, T cell infiltrates of skin and other affected organs and production of multiple autoantibodies. We have used our panel of mAbs to evaluate the thymic microenvironment in these autoimmunity-prone chickens. A comparative analysis with control chickens revealed striking deficiencies in the L200 subcapsular regions coupled with excessive expression of MHC class II antigens, particularly in the cortex. We hypothesize that these abnormalities induce altered T-cell differentiation, thereby predisposing the L200 chickens to autoimmune disease. PMID- 1883484 TI - The effect of anti-oestrogens on cell growth and progesterone receptor concentration in human endometrial cancer cells (Ishikawa). AB - The effect of two anti-oestrogens, 4-OH tamoxifen and ICI 164,384, on growth and progesterone receptor (PR) concentration was investigated in the endometrial carcinoma cell line, Ishikawa. Growth stimulation in response to 4-OH tamoxifen was antagonized by ICI 164,384, the latter having no agonist effect when used as a single agent. Similarly, ICI 164,384 antagonized oestradiol-stimulated cell growth. PR was significantly increased following treatment with 4-OH tamoxifen, this response being antagonized in the presence of ICI 164,384. Oestradiol increased PR, although to a lesser extent than did 4-OH tamoxifen; the effect of oestradiol on PR was also antagonized by ICI 164,384. Used as a single agent, ICI 164,384 induced a moderate but statistically significant increase in PR, thus demonstrating partial agonist activity. This agonist property of ICI 164,384 may provide a mechanism of maintaining PR, which is down-regulated during conventional progestin therapy, without undesirable mitogenic activity. PMID- 1883485 TI - Expression, purification and characterization of secreted recombinant human insulin-like growth factor-I (IGF-I) and the potent variant des(1-3) IGF-I in Chinese hamster ovary cells. AB - Recombinant human insulin-like growth factor-I (hIGF-I) and a biologically potent variant lacking the N-terminal tripeptide (des(1-3)IGF-I) were produced from transfected Chinese hamster ovary cells. The constructs encoding the signal peptide, sequence of the mature peptide and a C-terminal extension peptide were expressed under the control of a Rous sarcoma virus promoter. Successfully transfected clones secreting correctly processed recombinant hIGF-I or des(1 3)IGF-I were selected by their secretion of IGF-I-like activity into the culture medium. The recombinant peptides were purified to homogeneity as assessed by high performance liquid chromatography and N-terminal sequence analysis. The purified recombinant peptides exhibited biological potencies equivalent to authentic IGF-I and des(1-3)IGF-I respectively. PMID- 1883486 TI - Evidence for the involvement of multiple signalling pathways in C5a-induced actin polymerization and nucleation in human monocyte-like cells. AB - The signal transduction mechanisms involved in complement fragment C5a-induced recruitment of actin to the cytoskeleton have been investigated using U-937 cells differentiated by exposure to dibutyryl cyclic AMP. Two parameters of cytoskeletal activation were compared: F-actin formation and nucleation of polymerization of pyrenyl-actin in whole cell lysates. The dose dependency of these responses to C5a was clearly different to that observed for [3H]inositol phosphate formation and also markedly different from that observed for the production of reactive oxygen intermediates (ROI). Further evidence to dissociate inositol lipid hydrolysis from these cytoskeletal responses was obtained by treating cells with neomycin, phorbol myristate acetate and pertussis toxin and by modulating the levels of intracellular Ca2+ using quin 2. Inhibition of [3H]inositol phosphate and ROI production was not correlated with effects on actin recruitment or nucleation. In addition, these agents had differing effects on F-actin formation and nucleation activity. The results show that the production of inositol phosphates is not required for stimulating either F-actin formation or nucleation activity and also that ligand-induced polymerization of actin depends primarily upon an increase in the availability of G-actin rather than nucleation sites. These cytoskeletal responses are apparently controlled by different signalling pathways which diverge at an early stage. PMID- 1883487 TI - Self-inhibition of steroid secretion by amphibian adrenocortical cells is not mediated through glucocorticoid receptors. AB - To investigate a possible direct action of glucocorticoids on adrenal steroidogenesis, the effect of corticosterone on the conversion of pregnenolone into various metabolites by frog adrenal tissue was examined. Frog interrenal slices were incubated with [3H]pregnenolone (1 mCi/ml) and the various labelled metabolites analysed by reverse-phase high-performance liquid chromatography. With the methanol gradient used, five identified steroids were resolved: progesterone, 11-deoxycorticosterone, corticosterone, 18-hydroxycorticosterone and aldosterone. Corticosterone (10 micrograms/ml) induced a 45-80% decrease in all steroids synthesized from [3H]pregnenolone. In contrast, the glucocorticoid agonist dexamethasone did not reduce the rate of conversion of pregnenolone into its metabolites. In addition, the inhibitory effect of corticosterone was not reversed by the specific glucocorticoid antagonist RU 43044. These results show that corticosterone exerts a direct inhibitory effect on adrenal steroid secretion. In addition, our data indicate that the ultra-short regulation induced by corticosterone is not mediated through glucocorticoid receptors. PMID- 1883488 TI - Stimulation of an individual cell with peptide hormone in a prescribed region of its plasma membrane results in a compartmentalized cyclic AMP-dependent protein kinase response. AB - This work describes the stimulation by a peptide hormone of an individual cell in a prescribed region of its plasma membrane. When Leydig cells were stimulated via a section of membrane tightly sealed to an electrode containing LH, a very localized area exhibited the morphological change known as 'rounding up', which is a cyclic AMP-dependent protein kinase-mediated response. This localized stimulation did not produce a wider response through intracellular, intermembranous or extracellular signals. Each individual cell responded to peptide stimulation gradually, with an increase over time and with dose. In contrast, when the stimulation was accomplished using a non-hydrolysable cyclic AMP analogue in the patch electrode, a general response throughout an individual cell was produced. Locally stimulated peptide hormone receptors, adenylate cyclases and cyclic AMP-dependent protein kinases appear to be closely associated so that second messenger production and the effects it mediates are compartmentalized. PMID- 1883489 TI - Expression of parathyroid hormone-related protein mRNA in the rat before birth: demonstration by hybridization histochemistry. AB - The ontogeny of parathyroid hormone (PTH) and PTH-related protein (PTHrP) gene expression was studied by hybridization histochemistry in the rat at various stages between implantation and full term. PTHrP mRNA was demonstrable in the early postimplantation trophoblastic giant cells but disappeared from this site before 13.5 days. Localized gene expression, detectable by the in-situ technique, began between 12.5 and 15.5 days in embryonic tissues. The distribution of gene expression suggests that PTHrP may be concerned with the process of implantation. Its widespread, yet clearly localized, distribution in embryonic and fetal tissues is consistent with a paracrine or autocrine function which may relate to the transforming growth factor-beta family of growth factors. PTH expression occurred solely in the parathyroid and was detectable in the fetal parathyroid at 13.5 days of gestation. PMID- 1883490 TI - Differences in properties of the sheep testicular LH and FSH receptors. AB - Differences in binding and structural properties of ovine testicular FSH and LH receptors were investigated. The ovine FSH receptor did not discriminate between FSH of different species, although equine FSH was more reactive. In the same tissue, however, the LH receptor showed marked preference for ovine and bovine LH, reacting very weakly with other preparations of pituitary LH. Human chorionic gonadotrophin also reacted partly with the ovine LH receptor at 25 degrees C. However, at 4 degrees C, the optimum temperature for binding of the LH receptor to its homologous hormone, the receptor displayed no recognition for chorionic gonadotrophin preparations. Affinity cross-linking studies with ovine testicular membrane suggested that the ovine FSH receptor has an Mr of 70,000, which is very similar to that observed in the porcine ovary. The Mr of the ovine LH receptor was estimated to be 150,000, which is different from those of other mammalian species, including those that have been cloned. The data suggest that the binding and structural properties of the ovine FSH receptor are similar to those of other mammalian FSH receptors, whereas the ovine LH receptor appears to differ from other mammalian LH receptors in having a different Mr and in being more stringent in its requirement for pituitary LH. PMID- 1883491 TI - [An investigation on the resources of medicinal fungi in Sichuan]. AB - This paper reports the classification, distributional traits, new distribution, specific species of medicinal fungi, as well as the status of anticancer medications and edible and medicinal fungi in Sichuan. Rational suggestions have been made with regard to the cultivation, development and utilization of those important species with proven curative effect. PMID- 1883492 TI - [Identification of tinglizi by derivative spectrum]. AB - This paper reports a study on the application of derivative spectrum to the identification of tinglizi and its adulterants. The spectra of two normal species of tinglizi have been found identical, but those of six adulterants obviously different from the normal. PMID- 1883493 TI - [Status of Yunnan drug banxia and its botanical origin]. AB - L. Yunnan, the medicinal material Banxia recorded in The Pharmacopoeia of the People's Republic of China (1985 ed.) is called "Dizhu Banxia" (stem tuber of Pinellia ternata). Besides, "Shanzhu Banxia" (stem tuber of Arisaema yunnanense, A. bathycoleum, A. saxatile and A. prazeri) is also used medically as Banxia, while "Gouzhua Banxia" (stem tuber of Arisaema franchetianum, A. likiangense and Pinellia pedatisecta) is not. PMID- 1883494 TI - [Effect of vesicular-arbuscular mycorrhizal fungi on growth, nutrient uptake and synthesis of volatile oil in Schizonepeta tenuifolia briq]. AB - Inoculating Schizonepeta tenuifolia with VA mycorrhizal fungi can significantly improve the plant growth and uptake of P and S, and influence the absorption of K, Na, Fe, Mo, Mn, Zn, Co, Ba, Ni and Pb. It is interesting to note that VA mycorrhiza can also increase the synthesis of volatile oil in the shoots of S. tenuifolia. The efficiency of VA mycorrhiza varies with the fungal species. PMID- 1883495 TI - [Germination temperature of seeds of medicinal plants]. AB - According to our experiments in the last ten years, the germination behaviour of the seeds of medicinal plants may be classified into five types by different temperature requirements for germination: (1) low temperature type; (2) middle temperature type; (3) high temperature type; (4) alternating temperature type; (5) wide ranging temperature type. This classification is helpful for cultivators to determine the time of sowing. PMID- 1883496 TI - [Research on the processing of Angelica based on the analysis of water soluble constituents]. AB - In this paper, a comparative study on the contents of water-soluble and alcohol soluble tannin and ferulic acid in Angelica and its processed products is reported. The result shows that different processing methods have significant effects on the above constituents, thus administering to the interpretation of the theory of Angelica processing. PMID- 1883497 TI - [Experimental studies on the decoction siwu tang]. AB - Using many kinds of modern instruments, we have measured the content of ferulic acid, eight trace elements, seventeen amino acids and water-soluble substances in various single drug decoctions, group-drug decoctions, and mixtures of various single drug decoctions of radix Angelicae sinensis, radix Rehmanniae, radix Paeoniae alba and Rhizoma chuanxiong that make up the decoction siwu tang. Absorption peaks in ultraviolet spectra have also been measured. PMID- 1883498 TI - [Toxic principles of Oxytropis glabra DC]. AB - Eight alkaloids were isolated from Oxytropis glabra and identified as anagirine, thermopsine, N-methylcytisine, sparteine, baptifoline, adenine, dictamnine and ethyl allophanate respectively by spectral analysis and physicochemical methods. All these alkaloids were isolated from this genus for the first time and ethyl allophanate was found in nature for the first time. PMID- 1883499 TI - [Isolation and physico-chemical properties of polysaccharides from the root of Cynanchum auriculatum Royle ex Wight]. AB - Three polysaccharides AC-A, AC-B, AC-C were isolated and purified from the water extract of the root of Cynanchum auriculatum. The molecular weight of AC-A, AC-B and AC-C were 28000, 51000 and 117000 respectively. All these polysaccharides were composed of rhamnose, arabinose, xylose, galactose, mannose and glucose. PMID- 1883500 TI - [Determination of cholic acid in man-made bezoar by derivative spectrometry]. AB - Cholic acid in man-made bezoar can be determined by the suggested first order derivative spectrometric method. The peak amplitude within 310-290 nm is independent of the other components and only varies linearly with cholic acid concentration. The method is simple and accurate with good reproducibility. PMID- 1883501 TI - [Application of uniform design to pharmacological experiments of traditional Chinese medicines]. PMID- 1883502 TI - [Effect of rhizoma Zingiberis on anoxic or cooled mice]. AB - The anti-anoxic experiments have indicated that the petroleum ether extract of Rhizoma Zingiberis can prolong the survival time in mice poisoned by KCN or under the condition of normobaric hypoxia, as well as decapitation-induced gasping duration in mice, but can not prolong the survival time in mice poisoned by NaNO4. The anti-anoxic action might be related to the reduction rate of O2 consumption of the body. The aqueous extract of Rhizoma Zingiberis does not possess the above-mentioned anti-anoxic action. Both extracts do not affect the survival time in cooled mice. PMID- 1883503 TI - [Pharmacological studies on the volatile oil isolated from the leaves of Pinus pumila (Pall.) Regel]. AB - The sedative, analgesic, antipyretic and anti-inflammatory activities of the volatile oil isolated from the leaves of Pinus pumila are reported, the volatile oil being administered ip or po. The ip LD50 in mice was 0.577 +/- 0.056 ml/kg. PMID- 1883504 TI - [Effect of liuwei dihuang decoction and its compatible prescriptions on lipid peroxide and lipofuscin]. AB - Our experiment has shown that liuwei dihuang Decoction can decrease the contents of lipid peroxide in the serum as well as lipofuscin in the liver of the older mice to the level of the younger ones, while the two compatible prescriptions derived from the decoction, "Three invigorators" and "Three purges", cannot produce the same effect. All the three forms of prescription have no action on the lipofuscin in the heart. PMID- 1883506 TI - [Research on the improvement of dosage forms of prescriptions in Chinese traditional medicine]. PMID- 1883505 TI - [A study on components and compound prescription of huangqin decoction]. AB - The results obtained from the pharmacological experiments have preliminarily demonstrated that the compound prescription is better than its individual component drug in the range and potency of pharmacological activities. In the prescription Radix Scutellariae plays a principal role in pharmacological effects. Radix Scutellariae and Radix Paeoniae Alba can potentiate each other. Radix Glycyrrhizae and Fructus Jujubae in the compound prescription also exhibit biological activities to some extent. The relieving effect of the prescription for spasm and pain may result from the synergistic interaction between Radix Paeoniae Alba and Radix Glycyrrhiza, and the heat clearing and diarrhea stopping action is due to the biological activity of Radix Scutellariae. PMID- 1883507 TI - Structure and diversity of class I antigen presenting molecules in the mouse. AB - Sequence comparisons among class I genes provide insight into the nature and origins of diversity in the human and mouse MHC. The profiles of diversity among alleles and between different loci indicate that genetic interactions among class I genes generate sequence diversity in both species. Humans and mice differ in the extent that sequence transfer occurs between loci. In mice, sequences encoding the antigen binding domain show little evidence of locus specificity. A series of mouse class I mutants have been analyzed, providing strong evidence that interlocus gene conversion plays a significant role in the exchange of sequences among class I genes. A similar process is suspected in human class I and both mouse and human class II genes. However, the transfer of sequence among genes in these groups appears to occur predominantly between alleles and only to a minor extent between loci. PMID- 1883508 TI - Synthesis of complement components C2 and C4 by human monocyte-derived macrophages during in vitro differentiation in serum-free culture conditions. AB - In order to analyze the kinetics of complement component synthesis by human monocytes/macrophages, we have developed a system of defined culture conditions in the absence of serum. Moreover, the use of the polymerase chain reaction (PCR) provides a high sensitivity for the detection of mRNAs and the study of the regulation of complement component synthesis by these cells. Human blood monocytes were collected and purified by cytapheresis and elutriation, and then cultured in nonadherent cell culture bags for up to 3 weeks. Cells were grown in Iscove's modified Dulbecco's medium supplemented with alpha-phosphatidylcholine, transferrin, insulin, glutamine and antibiotics. The phenotypic and functional properties of macrophages differentiated under these serum-free culture conditions have been previously analyzed [1]. Secretion of complement component was measured by a hemolytic assay. mRNA was prepared using guanidine isothiocyanate extraction followed by cesium gradient ultra-centrifugation. cDNA was obtained by reverse transcription, then amplified by PCR. Fresh monocytes did not display any secretion of C2 as measured by hemolytic assay. However, C2 secretion was detected on and after the 3rd day of serum-free cultured unstimulated monocytes. The rate of C2 production increased along with macrophage differentiation up to the 3rd week of culture. We were not able to detect any functional C4 secretion. In preliminary studies, C2 and C4 mRNAs were detected in macrophages and in unstimulated fresh monocytes. These preliminary studies show that the serum-free culture conditions we have developed allow very satisfactory survival and differentiation of human monocytes, and provide optimal conditions for the study of their secretory activity. PMID- 1883509 TI - The macrophage in tuberculosis: sinner or saint? The T cell decides. AB - Immunity to intracellular bacteria including Mycobacterium tuberculosis crucially depends on intricate interactions between T lymphocytes and macrophages. Before contact with T lymphocytes macrophages serve as habitat for M. tuberculosis organisms; after activation by T cells they become major effectors against these pathogens. T cells comprise different subsets which express different functional activities. This paper describes evidence that different T cell subsets (CD4 alpha/beta T cells, CD8 alpha/beta T cells and gamma/delta T cells) as well as different T cell functions (interleukin secretion and target cell lysis) contribute to immunity against tuberculosis. PMID- 1883510 TI - Phagocytosis and heat shock response in human monocytes-macrophages. AB - The heat shock response represents a general physiological cellular reprogramming of gene expression secondary to exposure to multiple different stresses such as heat or oxygen free radicals. It is assumed that this response is turned on in order to protect cells, or to permit better recovery, from the detrimental effects of such stresses. During erythrophagocytosis, heat shock proteins and heme oxygenase synthesis are induced in human monocytes-macrophages. Whereas induction of heme oxygenase appears to be related to the hemoglobin-released iron, the factor(s) responsible for heat shock protein induction remain elusive. The respective roles of phagocytosis itself, oxygen free radicals, calcium, cytoskeletal alterations and oncogene expression are discussed. PMID- 1883511 TI - Intracellular pathogens and professional phagocytes in reactive arthritis. AB - Reactive arthritis is a postinfectious complication which develops after certain infections, mostly gastrointestinal or urogenital. Antigenic structures of the causative microbes, but no live organisms, have been demonstrated in inflamed joints. The host factors as well as the microbial antigens responsible for the initiation of the arthritic process are unknown. The pathogenesis of reactive arthritis is discussed here with special reference to the intracellular life of the causative microbes and to monocytes/macrophages, which may be involved in early events of the arthritic process as well as in maintenance of the autoimmune type of responses. PMID- 1883512 TI - Low incidence of transplant-related complications in patients with chronic release of tumor necrosis factor-alpha before admission to bone marrow transplantation: a clinical correlate of cytokine desensitization? AB - To investigate the role of tumor necrosis factor-alpha (TNF-alpha) released by activated macrophages, sequential serum samples of 120 patients undergoing bone marrow transplantation (BMT) were analyzed by enzyme-linked immunosorbent assay. De novo increases in serum TNF-alpha levels were correlated with the development of acute endothelial complications as well as acute graft-versus-host disease. In addition, the analysis of time courses revealed a different capacity of TNF-alpha regulation at various phases of BMT. While patients with acute TNF-alpha release in the first 2 weeks of BMT had a significantly enhanced incidence of complications, a subgroup of 9 patients with chronic asymptomatic release of TNF alpha before admission to BMT was observed. These patients were protected from complications in the course of the first 6 months of BMT. Our observations indicate the occurrence of desensitization for TNF-alpha, as it is also reported after repeated injections of TNF-alpha or endotoxin in experimental models. PMID- 1883513 TI - Regulatory mechanisms of host responsiveness to endotoxin (lipopolysaccharide). AB - During Gram-negative endotoxemia, precise regulation of monocyte/macrophage (M phi) responsiveness to lipopolysaccharide (LPS) is critical to preserve host defense while avoiding complications such as organ failure and death. We will discuss regulation of LPS-M phi interactions by LPS-binding plasma proteins and by LPS-induced changes in M phi responsiveness. Upon exposure to plasma, LPS binds to either lipoproteins or LPS-binding protein (LBP; a 60-kilodalton glycoprotein with a high-affinity binding site for the lipid A moiety of rough and smooth LPS). The LPS-LBP complex stimulates the M phi by binding to its cellular receptor, CD14 (a monocyte/M phi-specific, phosphatidylinositol-anchored surface glycoprotein). Pretreatment of whole blood with anti-CD 14 monoclonal antibody reduces the responsiveness of monocytes to LPS [determined by tumor necrosis factor-alpha (TNF-alpha) release]at least 10-fold. Similarly, cellular responsiveness to LPS is diminished at least 100-fold by depletion of plasma LBP with anti-LBP antibody. Compared to LPS-LBP induction of TNF-alpha, LPS lipoprotein complexes are as much as 10,000-fold less active. Thus, partitioning of LPS between LBP and lipoproteins markedly influences M phi responsiveness to LPS. LPS also directly induces M phi hyporesponsiveness to itself by a process known as adaptation; exposure of M phi to less than or equal to LPS/ml (subthreshold for TNF induction) for 6-9 reduces the sensitivity of the M phi to subsequent challenge up to 1,000-fold, so that 1 microgram/ml rather than 1 ng/ml of LPS is required for maximal induction of TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883514 TI - Lipopolysaccharide-instructed, cryopreserved, human monocytes sequentially convert plasma fibrinogen to fibrin and lyse the fibrin formed. AB - Cryopreserved human monocytes have been examined for their procoagulant and profibrinolytic capacities on lipopolysaccharide (LPS) stimulation, when given the possibility to act upon fibrinogen in heparinized plasma. As shown by the appearance of fibrinopeptide A, indicating thrombin action on the fibrinogen molecule, and by the appearance of D-Dimer, indicating the action of plasmin on fibrin, it is apparent that LPS-instructed monocytes give rise to fibrin which is subsequently lysed. Thus, delineation (fibrin formation) appears to be followed by fibrin removal (restitution). PMID- 1883515 TI - Regulation of cytokine and viral gene expression in monocytes infected with the human immunodeficiency virus. AB - Monocytes treated with interferon-alpha (IFN-alpha) at virus challenge show no evidence of human immunodeficiency virus (HIV) infection: no p24 antigen or reverse transcriptase (RT) activity, no viral mRNA and no proviral DNA. Levels of p24 antigen and RT activity in monocytes infected with HIV 1-3 weeks before IFN alpha treatment gradually decrease to baseline. HIV-induced cytopathic changes are markedly reduced, as are levels of HIV mRNA: the frequency of productively infected cells is less than or equal to 1%. But, levels of proviral DNA in the IFN-alpha-treated and control HIV-infected cells are indistinguishable, and remain so through 3 weeks. Large quantities of proviral DNA in IFN-alpha-treated cells with little active transcription suggest true microbiological latency. The major potential source for IFN-alpha in HIV-infected patients is the macrophage. With any of 15 virus isolates, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, IFN-omega or IFN-beta are not detected nor the mRNA expressed in HIV-infected or uninfected monocytes. Both uninfected and HIV-infected monocytes produce high levels of these cytokines after treatment with synthetic double stranded RNA (poly-I:C). Uninfected monocytes also produce high levels of IFN alpha after treatment with Poly-I:C, Newcastle disease virus or herpes simplex virus. In marked contrast, HIV-infected monocytes express no IFN-alpha activity or mRNA before or after treatment with any of these agents. The markedly diminished capacity of HIV-infected monocyte to produce IFN-alpha reflects a specific transcriptional block and may be an adaptive mechanism of virus to alter basic microbicidal functions of this cell.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883516 TI - AIDS encephalopathy and tropism of HIV for brain monocytes/macrophages and microglial cells. AB - HIV induces severe dementia in about 20% of adult AIDS patients. In children HIV infected at birth, the incidence of specific neurological complications is still higher since severe encephalopathy occurs in almost all children who develop an early and severe immunosuppression. In all cases, the brain monocytes/macrophages and the microglial cells are the only cells which replicate HIV in the central nervous system (CNS) of these patients, and the appearance of neurological symptoms seems induced by an interaction between HIV-infected macrophages with neurons and glial cells. AIDS encephalopathy is related to two properties of HIV: to the viral tropism for monocytes/macrophages/microglial cells, which allow the brain infection, and to HIV tropism for CD4+ lymphocytes responsible for the appearance of immunosuppression, which trigger viral dissemination in the CNS. However, childhood encephalopathy is not always associated with HIV replication in the CNS at the time of death, and mild dementia in HIV-infected adults were described without signs of HIV replication in autopsy CNS samples. Those findings suggest that persistent, productive viral infection is not required for the development of HIV encephalopathy. Therefore, if the relationship between HIV CNS infection and AIDS encephalopathy in adults and children is clearly demonstrated, the pathogenesis of the neurological disease and the kinetics of HIV replication in the CNS are unclear. In addition, the very high incidence of AIDS encephalopathy in children could be related to HIV infection of microglia which is differentiating in fetal or newborn brain. PMID- 1883517 TI - Interaction of cultured human Kupffer cells with HIV-infected CEM cells: an electron microscopic study. AB - Evidence has accumulated indicating that macrophages could play a role in the physiopathology of AIDS. We recently demonstrated that cultured human liver macrophages, the so-called Kupffer cells (KC), are permissive for HIV. Their infection in vivo would lead these cells to constitute a target for the virus and a reservoir as well. Since they occupy a strategic position within the liver sinusoid, their opportunity to interact with blood-borne virus or already infected T lymphocytes may be very high. In the present study, we investigated the possibility for KC to be infected via HIV-infected CEM cells, a lymphoid cell line. Therefore, we cocultured both cell types for various times before fixing them for electron microscopy. Syncytia appeared within 20 h of infection as well as a large amount of virus particles. HIV in the way of budding was also easily observed. This has to be compared to the direct infection of KC with free virus which needs, at least, about 10 days to give the same results. PMID- 1883518 TI - Influenza A virus infects macrophages and stimulates release of tumor necrosis factor-alpha. AB - The clinical picture of influenza A virus infections indicates that release of tumor necrosis factor-alpha (TNF-alpha) may be involved. In the present study we exposed the murine macrophage line PU5-1.8 to influenza A virus and observed a productive infection which was followed by subsequent cell death. Infection of macrophages was accompanied by TNF-alpha mRNA accumulation and TNF-alpha release. TNF-alpha production could only be induced by live virus whereas interferon release was also stimulated by inactivated virus. When virus-infected macrophages were exposed to low amounts of lipopolysaccharide (LPS; 1-10 ng/ml) TNF-alpha production was strongly potentiated. These data show that low LPS concentrations could readily trigger a high TNF-alpha release from influenza-A-virus-infected macrophages which could, at least partially, explain the serious complications of combined influenza A virus and bacterial infections. PMID- 1883520 TI - Monocyte-mediated growth control and the induction of tumor cell death. AB - In the present article a hypothesis is put forward and supporting data are referred that explain the elimination of tumorigenic cells as a consequence of their failure to comply with the rules of ubiquitous negative growth control mechanisms involving among others also mononuclear phagocytes as effector cells. This hypothesis does not invoke the recognition of altered cell surface structures on tumorigenic cells as the basis for discriminating them from normal cells and thus avoids one of the most irritating problems of hypothetical tumor defense mechanisms involving the recognition of spontaneously arising tumor cells as 'non-self' by immunologic effector cells. PMID- 1883519 TI - The role of macrophages in the regulation of primary tumor growth. AB - Tumor-associated macrophages (TAM) represent a population of tissue macrophages with peculiar biological, biochemical and phenotypic properties. Here we have briefly analyzed two different mechanisms involved in the regulation of the levels of TAM: the production of tumor-derived chemotactic factors for mononuclear phagocytes and in situ proliferation of TAM. Two clones selected from the murine sarcoma line B77 showed a different capacity to produce the tumor derived chemotactic factor known as JE. Studies with these clones demonstrated a correlation between in vitro production of the protein JE, expression of JE mRNA and macrophage content in tumor tissues, suggesting that the production of chemotactic factors can play a role in the regulation of TAM accumulation. Moreover, it has been shown that TAM had high levels of proliferative activity compared to peritoneal exudate macrophages. In an effort to elucidate the mechanisms responsible for the proliferative activity of TAM, the expression of c fms and macrophage-colony-stimulating factor (M-CSF) was investigated in TAM and sarcoma cells. TAM had high levels of mRNA transcripts of the c-fms protooncogene, which encodes a tyrosine kinase probably identical to the M-CSF receptor, but did not express M-CSF transcripts, while sarcoma cells had high levels of M-CSF mRNA. Sarcoma-cell-conditioned medium had M-CSF activity on bone marrow cells: this activity was blocked by anti-M-CSF antibodies. These findings outline a paracrine circuit in the regulation of TAM proliferation, involving M CSF secreted by sarcoma cells and acting on c-fms-expressing TAM. A better understanding of the regulation and function of TAM may provide a less empirical basis for a rationale design of therapeutic approaches. PMID- 1883521 TI - Tumoricidal effector molecules of murine macrophages. AB - Activated macrophages secrete a variety of factors affecting proliferation or viability of neoplastic cells. Factors described previously are discussed for their relevance as effector molecules for the selective destruction of tumor cells by activated macrophages and compared to a recently characterized high molecular-weight tumoricidal activity secreted by activated murine bone-marrow derived macrophages. PMID- 1883522 TI - Antibody-mediated tumor cytotoxicity of microglia. AB - The status of microglial cells as potent effector cells in antibody-mediated tumor cytotoxicity (ADCC) could be established. Microglia (greater than or equal to 99.9% pure) derived from brain cortices of newborn mice were shown to lyse human tumor cell lines expressing different levels of epidermal growth factor (EGF) receptors in the presence of MAb 425, a monoclonal murine anti-primate EGF receptor antibody. MAb 425 mediates microglial ADCC (MiADCC) at concentrations as low as 10(-11) M. Antibody ligands binding unilaterally to either EGF receptors on target cells or Fc receptors on microglia have little effect on MiADCC. At 10( 10) M MAb 425, a 10(3)-fold excess of MAb 425 F(ab')2 fragments or irrelevant antibodies of identical isotype did not block MAb-425-induced MiADCC. Formation of effector-target cell contacts seems to be critical for MiADCC and MiADCC could not be inhibited by anti-tumor necrosis factor-alpha antibodies. In addition to its stimulatory effect on MiADCC, MAb 425 bound to EGF receptors exerted a microgliotrophic effect. Factor(s) derived from astrocytes enhance MiADCC. PMID- 1883523 TI - Adoptive immunotherapy with autologous macrophages: current status and future perspectives. AB - Adoptive immunotherapy is a treatment modality designed to correct a defective and/or insufficient host defense response to a malignant tumor. Recently, we have developed a large scale technology for the generation of tumor cytotoxic macrophages (MACs) from circulating precursor monocytes. These ex vivo matured and interferon-gamma-activated MACs were used for adoptive transfer in a total of 30 tumor patients by intravenous (n = 12), intraperitoneal (n = 11) and intrahepatic (n = 7) infusion. A biological response to autologous cell transfer was evident from low-grade fever, elevation of C-reactive protein, induction of the coagulation cascade and a rise in interleukin-6 in sera as well as in ascitic fluids. A clinical response was only seen upon intraperitoneal treatment and consisted of palliation of malignant ascites in 3 of 7 patients and in reduction of ascitic tumor markers (CEA, CA125). Future perspectives of MAC therapy in combination with macrophage colony-stimulating factor, bacterial endotoxins and synthetic derivatives as well as monoclonal antibodies against tumor-associated antigens are discussed. Furthermore, the ex vivo manipulation of the MAC system may offer the possibility to use these multifunctional, pleiotropic effector cells not only in malignancy but also for the therapy of complicated opportunistic infections and secondary bone marrow hypoplasia. PMID- 1883524 TI - Biochemistry and function of pteridine synthesis in human and murine macrophages. AB - We investigated intracellular pteridine concentrations, activities of pteridine biosynthetic enzymes and formation of nitrogen oxides from arginine in human peripheral-blood-derived macrophages and in myelomonocytoma (THP-1) cells, as well as in murine peritoneal and spleen-derived macrophages and in murine macrophage lines (P388-D1, J774-A.1). Interferon-gamma (IFN-gamma) induces the activity of GTP-cyclohydrolase I up to 40-fold in human cells. In human macrophages and THP-1 cells, this induced activity is higher than the constitutively present activity of the subsequent enzyme, the 6 pyruvoyltetrahydropterin synthase. As a consequence, large amounts of neopterin are formed during IFN-gamma-triggered synthesis of tetrahydrobiopterin. Murine macrophages constitutively synthesize tetrahydrobiopterin. The activity of GTP cyclohydrolase I remains unchanged by treatment with IFN-gamma or tumor necrosis factor-alpha. This activity is lower than the subsequent 6 pyruvoyltetrahydropterin synthase activity, thus explaining the lack of neopterin in murine cells, tissues and body fluids. Inhibition and reconstitution of pteridine synthesis in activated murine macrophages by specific drugs demonstrate that tetrahydrobiopterin regulates the amount of nitrogen oxides formed from arginine in intact cells, thus providing a rationale for therapeutic intervention. PMID- 1883525 TI - Regulation of M-CSF expression by M-CSF: role of protein kinase C and transcription factor NF kappa B. AB - Macrophage-colony-stimulating factor (M-CSF), also referred to as CSF-1, regulates the survival, growth, differentiation and functional activity of monocytes by binding to a single class of high-affinity cell surface receptors, known to be the product of the c-fms protooncogene. The detection of both M-CSF and c-fms expression by cells of the monocyte lineage has suggested that M-CSF may act by an autocrine mechanism. Interestingly, it has been shown that M-CSF can induce the expression of its own gene. Although sensitivity to M-CSF can be modulated by regulation of receptor expression and function, M-CSF responsiveness is largely determined at a postreceptor level. To date, little is known about the intracellular pathway of M-CSF signal transduction. We have therefore investigated the changes in protein kinase C (PKC) activity upon exposure of monocytes to M-CSF. We show that M-CSF activates and translocates PKC. Inhibition of PKC by the isoquinoline derivative H7 abolishes induction of M-CSF by M-CSF. Furthermore, activation of PKC was pertussis-toxin-sensitive and was associated with the detection of an NF kappa B protein in nuclear extracts of M-CSF-induced blood monocytes but not in monocytes exposed to medium treatment only. The results suggest that M-CSF induction of M-CSF involves G proteins, PKC and NF kappa B. PMID- 1883526 TI - Hypercalcemia of malignancy: pathophysiology, diagnosis and treatment. AB - Malignancy is the most frequent cause of hypercalcemia in hospitalized patients. The pathophysiology of hypercalcemia of malignancy (HM) is complex. Increased bone resorption is involved in most cases caused either by extensive local bone destruction or by humoral factors. Tumor extracts from patients with humoral hypercalcemia of malignancy (HHM) often contain PTH-like bioactivity. Recently, cDNAs coding for a PTH-related protein (PTH-rP) has been cloned. The N-terminal amino acid sequence of this protein shows a considerable homology with human PTH. However, other bone resorbing factors including prostaglandins, transforming growth factors, colony stimulating factors, leucocyte cytokines and 1,25 dihydroxyvitamin D may be involved in different types of malignancy. HM is usually progressive with troublesome symptoms and a high mortality. Several treatment alternatives are available including rehydration, bisphosphonates, calcitonin, plicamycin, phosphate, and glucocorticoids. Others are under investigation. Treatment should be individualized taking into account the pathophysiological mechanisms involved, the extent of hypercalcemia and renal failure, and the prognosis related to the malignant disease. PMID- 1883527 TI - The hematopoietic microenvironment. AB - Hematopoietic microenvironment is comprised of an admixture of several adherent cell types including fibroblasts, reticular adventitial cells, and marcophages. The biologic interaction of these cells with the most primitive hematopoietic progenitor cells capable of reconstituting all hematopoietic lineages within an irradiated host, as well as differentiated progenitor cells and cells of each committed lineage, has been the subject of intense investigation. Transplantation of the hematopoietic microenvironment has recently been demonstrated and this technique has been used to partially correct the microenvironmental defect in the Sl/Sld mouse. The molecular mechanism of cell surface interaction between stromal and hematopoietic stem cells is being elucidated by molecular transfection techniques in which genes for specific receptors are introduced into hematopoietic stem cell lines and then demonstrated to adhere and proliferate in contact with stromal cells expressing transfected recombinant ligands. This model has been demonstrated with the EGF receptor bearing 32D cl 3 stem cells bound to TGF alpha-producing stromal cells. Extracellular matrix components of the adherent cell layer, the binding of hematopoietic growth factor interaction with matrix components, as well as the positive and negative feedback regulatory role of hematopoietic stem cells bound to the microenvironment, represents the focus of current investigation. PMID- 1883528 TI - Stabilizing effect of organic solvents on oxyhemoglobin. AB - The role of hemoglobin solutions as oxygen carriers in biotechnology are numerous, such as in the oxygen supply to biocatalysts or in the preparation of blood substitutes. However, the major barrier to the successful use of hemoglobin in biological and medical engineering is the autoxidation of heme iron during preparation, storage, and utilization. Fifty-six solvents, chosen among the group of Parker's classification, were studied with regard to the autoxidation kinetics of oxyhemoglobin under nondenaturant conditions. Among these solvents 27 present a concentration range in which the autoxidation rates were reduced compared to autoxidation in water. Three groups of solvent have been observed: one exhibiting only a destabilizing effect regardless of the solvent proportion, a second showing a strong stabilizing effect (k(H2O)/k(solvent) greater than 20) and a third showing a low stabilization (k(H2O)/k(solvent) less than 20). The most effective stabilizing solvents were glycerol, glycols, and alcohols. The effect of hydroorganic solvents could be explained by taking into account the globin solvation by water molecules. The solvents that enhance the structure of the water and form few hydrophobic interactions with globin prevent oxyhemoglobin autoxidation. PMID- 1883529 TI - Immunoaffinity partitioning: synthesis and use of polyethylene glycol-oxirane for coupling to bovine serum albumin and monoclonal antibodies. AB - Polyethylene glycol (PEG)-oxirane was synthesized by reacting aminated monomethoxy-PEG 5000 (NH2-MPEG 5000) with butanediol diglycidyl ether and used to derivatize bovine serum albumin (BSA) and monoclonal antibodies (mAb) against horseradish peroxidase (HRP) and porcine lactate dehydrogenase isoenzyme 5, respectively. Determination of oxirane end groups revealed a very high number, which arise from the chain breaks of the polymer. Covalent coupling of PEG oxirane to BSA resulted in 30-50 times higher partition coefficients under optimized conditions. The mAb investigated could be modified with PEG-oxirane while retaining its binding properties and could be used as an affinity ligand for selective extraction of Ag in immunoaffinity partitioning. However, a high degree of modification results in a lower binding constant of mAb anti-HRP and higher [mAb]/[Ag] concentration ratios in immunoaffinity partition experiments. PMID- 1883530 TI - Use of liposomes, viral capsids, and nanoparticles as DNA carriers. AB - We tested a variety of liposomes for parameters such as DNA binding capacity and DNase I protection of incorporated and attached DNA to elucidate their use as vehicles for DNA transfer into cells and animals. The results were compared to other potential DNA vehicles, empty viral capsids, and nanoparticles. Maximal binding capacity was achieved for positively charged nanoparticles, DNase I protection was observed for most preparations with neosome preparations being least efficient. The uptake of radiolabeled DNA by cells in culture was determined for cationic and nonionic surfactant vesicles, viral capsids, and nanoparticles. Cellular DNA uptake was best for dioleoyl-derived positively charged liposomes (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride; DOTMA) and the DNA could be shown to be physiologically active. The recombination rate for DNA fragments transfected in polyoma capsids in live mice was higher than for liposome mediated transfection. Homologous recombination could be observed for both DOTMA and polyoma-mediated DNA transfer. PMID- 1883531 TI - Solid-phase synthesis of biologically active fragment 29-111 of rat prothymosin alpha. AB - Rat prothymosin alpha fragment 29-111, an 83-residue polypeptide corresponding to desthymosin alpha 1-prothymosin alpha, has been synthesized by a solid-phase method. Hydrogen fluoride was used to deprotect and cleave the peptide from the resin. The crude product was purified by gel-filtration, ion-exchange chromatography and high-performance liquid chromatography. A 3.2-mg sample of a ca. 96% pure peptide was finally obtained. The overall yield of the synthesis was less than 1%. An increase of E-rosette-forming lymphocytes was obtained after incubation of peripheral blood from uremic patients with the synthetic prothymosin alpha fragment 29-111. The restoring effect of the synthetic prothymosin alpha fragment 29-111 was greater than that of our synthetic thymosin alpha 1. PMID- 1883533 TI - Gangliosides administration causes sugar moiety-specific enzymatic changes in brain. AB - Exogenous gangliosides are known to affect the metabolism when administered to the body. To study the mechanism of this effect three types of gangliosides were administered intraperitoneally to mice and the changes in the enzyme activity of the cerebral tissues studied. The effect of GM2 from bovine brain was characterized by a decrease in the activity of various aminopeptidases, while GD3 from cow's milk caused an increase in the activity of sugar-related enzymes such as sialidase, glucosidase, and fucosidase. GM3 from horse erythrocytes showed intermediate effects between GM2 and GD3. Multivariate analysis showed that the effects of the three gangliosides are clearly separable statistically. These results which demonstrate the sugar moiety-specificity of gangliosides are discussed in relation to the A and B pathways of ganglioside synthesis. PMID- 1883532 TI - Purification and characterization of recombinant human insulin-like growth factor II (IGF-II) expressed as a secreted fusion protein in Escherichia coli. AB - Human insulin-like growth factor II (IGF-II) was produced in an Escherichia coli ompT strain as a 22.5-kDa fusion protein. IGF-II was fused to the carboxy terminal of a synthetic 15-kDa IgG-binding protein, originating from staphylococcal protein A, via a unique methionine linker. During fermentation, the fusion protein was exported to the growth medium at levels exceeding 900 mg/liter and subsequently affinity purified on IgG Sepharose followed by ion exchange on S Sepharose. After chemical cleavage with CNBr, yielding an authentic IGF-II molecule, the recombinant IGF-II was purified to homogeneity by a two step procedure involving ion-exchange and reverse-phase HPLC. A substantial fraction of the secreted protein was found to be biologically active, eliminating the need for complex refolding procedures. The yield of highly purified and biologically active IGF-II was 5-7 mg/liter of fermenter broth. The IGF-II produced by this method displayed biochemical, immunological, receptor binding, and biological activity properties equal to those of native IGF-II isolated from human serum. PMID- 1883534 TI - Dental and oral disease in Lagomorphs. AB - The dental diseases of rabbits are unique because of their dental anatomy and physiology. Common problems of Lagomorph dentition are covered in this article including malocclusions, periodontal disease, and their treatment. The anatomy of Lagomorph dentition is reviewed and anesthesia protocols are included. PMID- 1883535 TI - Anaerobes in periodontal disease in the dog: a review. AB - As anaerobic sampling and culture techniques improved, the documented prevalence of anaerobic bacteria in periodontal disease has increased. The anaerobic bacteria have become more well-known in humans and consequently in dogs, since this species is a major model in periodontal studies. A review of the literature related to anaerobic flora is described. PMID- 1883536 TI - External odontoclastic resorptive lesions in cats--another opinion. PMID- 1883537 TI - Prosthodontic treatment of trauma to the nasus externus, premaxilla and maxilla of a dog. AB - This is a clinical report which presents a prosthodontic treatment for a trauma case in a dog with multiple dental, skeletal and soft tissue problems. The treatment resulted from investigations into prosthodontics with the assistance of a prosthodontic dental laboratory. The prosthesis which was fabricated solved the problem of obstructed airflow through an injured nares, and provided for an esthetic result. Treatment required intermittent procedures over a one year period. PMID- 1883538 TI - Effective slide presentations. AB - Veterinarians are often called upon to give lectures on a variety of subjects. The preparation of these lectures often includes the use of kodachrome slides to illustrate a subject. Often narrative slides and descriptional slides are necessary to complete an effective lecture. A description of preparing slides is detailed. PMID- 1883539 TI - Form, function, and use of retroviral gag proteins. PMID- 1883541 TI - Induction of dormant HIV-1 by sodium butyrate: involvement of the TATA box in the activation of the HIV-1 promoter. AB - Reactivation of latent HIV-1 is believed to play a major role in the pathogenesis of AIDS. Here we show that sodium butyrate (NaB), which can cause gene induction or cell differentiation, reactivates dormant HIV-1 in vitro in chronically infected cells of T-lymphoid and monocytoid origin. The effect of NaB on HIV-1 expression in T-lymphoid cells was apparent 3 h after addition of drug and peaked at 24 h. During this time the proportion of HIV-1 antigen expressing cells increased from less than 0.5 to greater than 90%, and virus production increased by three orders of magnitude. The virus released by the NaB-induced cells was infectious. The extent and kinetics of NaB effects were similar to effects of phorbol 12-myristate 13-acetate in T cells, but not monocytes. Transient expression assays using an indicator gene under the control of the HIV-1 long terminal repeat revealed that mutations which altered the nucleotide sequence in the TATA box significantly reduced the NaB effect. These data show that NaB is a potent inducer of dormant HIV-1 and suggest that the TATA motif is required for this activity. PMID- 1883540 TI - Efficacy of SIV/deltaB670 glycoprotein-enriched and glycoprotein-depleted subunit vaccines in protecting against infection and disease in rhesus monkeys. AB - Immunization with an inactivated whole-virus vaccine is highly effective in preventing lentivirus infection. The viral protein(s) essential to the induction of protective responses, however, have not been identified. To define the role of virion components in the induction of protective immunity, we evaluated the efficacy of glycoprotein-enriched and glycoprotein-depleted simian immunodeficiency virus (SIV) subunit vaccines prepared by lentil-lectin affinity chromatography of gradient-purified virions using the immunization and challenge regimen previously found successful with an inactivated whole-virus vaccine. Infection was determined by successful recovery of virus, the induction of SIV specific antibody responses, and infection of naive recipients by inoculation with lymph-node-derived lymphocytes from the vaccinates. Immunization with the glycoprotein-enriched preparation prevented infection in two out of four monkeys, whereas the glycoprotein-depleted vaccine failed to prevent infection in all four vaccinates tested. However, the glycoprotein-depleted vaccine appeared to moderate the progression of SIV-induced disease compared with non-immunized infected control monkeys inoculated with the same challenge dose. These data suggest that subunit vaccines containing sufficient quantities of viral glycoproteins can protect against SIV infection, whereas subunit vaccines composed predominantly of viral core proteins cannot. The development of effective vaccines against HIV infection should include studies on the optimum presentation of the viral envelope glycoproteins to produce long-term broadly protective immune responses. PMID- 1883542 TI - Evidence from Zaire that breast-feeding by HIV-1-seropositive mothers is not a major route for perinatal HIV-1 transmission but does decrease morbidity. AB - Breast-feeding as a route of HIV-1 transmission during infancy but also as a protective measure against early childhood morbidity has been investigated prospectively in children born to HIV-1-seropositive mothers and control children born to age- and parity-matched HIV-1-seronegative women. The mothers of all study children had been enrolled antenatally at a maternity hospital in Kinshasa, Zaire, which served a relatively affluent group of women who sometimes chose not to breast-feed their infants. In 106 children born to HIV-1-seropositive women, the rate of HIV-1 transmission was 21% in 28 infants exclusively breast-fed, 19% in 68 infants both breast- and bottle-fed and 0% in 10 infants who were bottle fed only (P = 0.35). In contrast, non-HIV-1-infected children of both HIV-1 seropositive and HIV-1-seronegative mothers who were exclusively breast-fed compared with uninfected children who were not exclusively breast-fed had significantly lower incidence rates of acute diarrhea, fever and lower respiratory tract infection. The lack of a dose-response effect between breast feeding and perinatal HIV-1 transmission and the presence of a protective effect of breast-feeding against common causes of early childhood morbidity and mortality support the current World Health Organization recommendation that breast-feeding should continue to be promoted in all developing countries, including those with high HIV-1 prevalence rates in women of childbearing age. PMID- 1883544 TI - Sexual partners, penetrative sexual partners and HIV risk. AB - This paper argues that the notion of sexual partners per se is insufficient for estimating levels of HIV risk behaviour or changes in HIV risk over time, even though it is a crucial element of most epidemiological models of HIV. The concept of a penetrative sexual partner (PSP) is introduced as a considerably more accurate measure of HIV risk. Using data from a longitudinal study of 930 homosexually active men in England and Wales, this paper demonstrates that variation in numbers of PSPs (and thus HIV risk) is not related to variation in the gross numbers of sexual partners. PMID- 1883543 TI - HIV and other sexually transmitted diseases among female prostitutes in Kinshasa. AB - In 1988, 1233 prostitutes from different geographic areas of Kinshasa participated in a cross-sectional survey on HIV infection and other sexually transmitted diseases (STDs). Despite relatively good knowledge about AIDS and STDs, the reported preventive behaviour was poor. Only 12% of the women reported regular use of condoms, while greater than 50% of the women reported regular use of antibiotics and 38% reported doing nothing specific to prevent STDs. Thirty five per cent of the women were HIV-positive compared with 27% in a similar survey in Kinshasa in 1986. The prevalence of other STDs was very high, ranging from 5% for genital ulcer disease (GUD) to 23% for gonococcal infection. HIV positive women were older than HIV-negative women (26.9 versus 25.4 years; P less than 0.001), had a significantly lower level of reported condom use (9 versus 14%, P = 0.009), and reported more frequent use of antibiotics to prevent STDs (55 versus 42%, P = less than 0.001). The prevalence of syphilis, gonorrhoea, chlamydial infection and trichomoniasis was not higher in HIV-positive women compared with HIV-negative women. However, HIV-positive women had a higher prevalence of GUD (9 versus 3%, P less than 0.001), antibodies against Haemophilus ducreyi (82 versus 57%, P less than 0.001), antibodies against herpes simplex virus type 2 (96 versus 76%, P less than 0.001), condylomata accuminata (5 versus 1%, P = 0.003) and cytologic evidence of human papilloma virus on Papaniclaou cervical smear (11 versus 5%, P = 0.006). This study confirms the high incidence of HIV and other STDs among prostitutes in Africa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883546 TI - Development of language in 18-30-month-old HIV-1-infected but not ill children. AB - Thirty-six children (age range, 18-30 months) born to HIV-1-infected mothers were studied for speech development by matching 18 infected with 18 non-infected subjects for age, sex and socioeconomic status. All the children were in good health. Each child was given three comprehension and three production tasks. In addition, each child's mean length of utterance (MLU) was obtained by observation of natural child-parent interactions. The development quotients (DQ) were assessed by Brunet-Lezine's tests. Infection significantly affected children's MLU, the infected children being less advanced than those non-infected. Both infected and non-infected children progressed in language acquisition from the second to the third year of age, but infected children had significantly greater production difficulty than non-infected children in the second year of life. The matched subjects design adopted gives some strength to the conclusion that HIV-1 infection impairs the genesis rather than the later development of language in infected but not ill children. PMID- 1883545 TI - Endocrine function in 98 HIV-infected patients: a prospective study. AB - Endocrine function was prospectively evaluated in 98 patients (73 men and 25 women) infected by HIV in various stages of illness: Centers for Disease Control groups II (19), III (20), IVA and IVC2 (27), IVC1 and IVD (32). Testing included baseline and post-stimulation evaluation of gonadal, thyroidal, and adrenal axes. Although adrenal function was within normal values in most cases, with no differences between patient groups, nine out of 98 patients had either a low baseline or post-stimulation serum cortisol, cytomegalovirus adrenalitis being suspected in two cases. Mineralocorticoid response was normal in all individuals. The main abnormalities were sick euthyroid syndrome with low tri-idothyronine and/or thyroxine in 16% of patients and hypotestosteronemia in 29% of men with AIDS. These abnormalities, related to a functional deficiency of the hypothalamic pituitary axis, were highly correlated with the degree of illness, i.e. weight loss and low CD4+ cell count. It was concluded that endocrine dysfunction in HIV infected patients is rarely of clinical significance, that it is related more to cachexia and advanced disease than to HIV or opportunistic infections, and that it could serve as a prognostic marker. PMID- 1883547 TI - Relapse in sexual behavior among homosexual men: a 2-year follow-up from the Chicago MACS/CCS. AB - Serial biannual cross-sectional assessments of HIV sexual risk indicated a consistent increase in safer sexual practices among homosexual men participating in the Chicago-Multicenter AIDS Cohort Study (MACS)/Coping and Change Study (CCS) in 1986-1988. Safer sexual practices were achieved by avoidance of anal sex and less often by consistent use of condoms. Longitudinal patterns of variability in individual behavior were also assessed. After 1 year of follow-up, 53% of the participants maintained safer practices in receptive anal sex, 6% maintained unsafe practices, while 31% relapsed at least once. After 2 years, 45% maintained safer practices, 3% maintained unsafe practices and 47% relapsed at least once. Similar trends were observed in insertive anal sex. PMID- 1883549 TI - HIV-1 infection of CD4-negative cells via HTLV pseudovirons. PMID- 1883548 TI - Successful management of intractable cryptosporidial diarrhea with intravenous octreotide, a somatostatin analogue. AB - A 38-year-old man with AIDS and intractable large-volume diarrhea due to a cryptosporidial infection was successfully treated with intravenous octreotide, a somatostatin analogue. The volume of diarrhea, 10-12 liters with 8-13 movements per day, was reduced to three to four semi-formed to formed stools per day when the patient was treated with 400 micrograms intravenous octreotide daily. The patient's intravenous hyperalimentation was discontinued and he returned to oral feeding. He quickly regained his normal weight and has now resumed his normal activities. For those patients who cannot tolerate subcutaneous administration, intravenous octreotide therapy may not only be life-saving but may also markedly increase the quality of life. Roxithromycin, a macrolide antibiotic, was also administered to this patient with cryptosporidiosis but efficacy was not demonstrated. PMID- 1883550 TI - Gp160 of commercial HIV western blots is not gp160env. Should criteria for seropositivity be revised? PMID- 1883551 TI - Evidence of HTLV-II infection in central Africa. PMID- 1883552 TI - Drug sharing among intravenous drug users. PMID- 1883553 TI - Hospital-based surveillance of HIV infection: Bordeaux, France, 1983-1990. Groupe d'Epidemiologie Clinique du SIDA en Aquitaine (GECSA) PMID- 1883554 TI - The use of corticosteroids in the control of the adverse effects of cotrimoxazole in AIDS patients suffering from PCP. PMID- 1883556 TI - Seroepidemiological survey of transmissible infections in Portuguese prisoners. PMID- 1883555 TI - No histological evidence for cytotoxic T cells in destruction of lymph-node follicle centres after HIV infection? PMID- 1883557 TI - A seroepidemiological survey of HTLV-I infection in Shanghai and Chongqing cities in China. PMID- 1883558 TI - CTS. PMID- 1883559 TI - Keep office harmony by following these 10 rules for playing fair. PMID- 1883560 TI - Advances in computer technology make life a bit easier in the office. PMID- 1883561 TI - Knowing how to approach the media can help you attract new patients. PMID- 1883562 TI - Discipline system improves performance, avoids dismissals. PMID- 1883563 TI - Risky business. PMID- 1883565 TI - Doctors seeking partnerships should take buy-and-sell subject seriously. PMID- 1883564 TI - Desensitizing teeth doesn't have to be a sensitive matter for patients. PMID- 1883567 TI - Review your procedures for dismissing employees to make sure they're fair. PMID- 1883566 TI - There's a new generation of adhesives that will bond to just about anything. PMID- 1883568 TI - We want you ... but are dentists willing to pay the price? PMID- 1883569 TI - The office works best when the front and back staffs work in tandem. PMID- 1883570 TI - Endo trays with all necessary items makes filling process smoother, faster. PMID- 1883571 TI - To lease or not to lease? That's a taxing question for dentists. PMID- 1883572 TI - Using the right words encourages patients to accept treatment plan. PMID- 1883573 TI - Breaking down the barriers. PMID- 1883575 TI - A knowledgeable staff is best marketing tool a dentist can have. PMID- 1883576 TI - Contracts excellent way to inform patients about treatment risks, results. PMID- 1883574 TI - Disinfecting impressions, prosthetics key to thorough infection control. PMID- 1883577 TI - Florida AIDS cases raises ethical questions for healthcare professionals. PMID- 1883578 TI - Pediatric trauma. PMID- 1883579 TI - The epidemiology of pediatric trauma. AB - Trauma is the leading cause of death in children. Children in the toddler and preschool age groups are more prone to falls, poisonings, and foreign body aspirations, whereas school-age children are more likely to be involved in pedestrian and bicycle accidents. In all age groups, males are more likely to receive injuries than females. Major mechanisms of injury include motor-vehicle- occupant and -pedestrian accidents, bicycle accidents, and falls. Most injuries are blunt in nature and occur to the central nervous system, musculoskeletal system, and thoracic-abdominal area. Head injuries account for most of the injuries and fatalities in pediatric multiple trauma patients. PMID- 1883580 TI - The nurse's role in pediatric injury prevention. AB - Nurses can play a major role in injury prevention. Nurses are, by nature, educators and role models to their families, patients, and communities. Knowing the magnitude and impact of injuries on both children and their families, nurses must become more informed about the necessity of injury prevention. They must also help to initiate and develop prevention strategies that will decrease the number and severity of these injuries. There is a connection between clinical work and advocacy. Nurses see the pain and problems created by injuries. They can become effective advocates for injury prevention because the strongest advocacy is created by those closest to the problem and most aware of what is needed. Nurses need to become involved in identifying unsafe products and environments and testifying before regulatory and legislative bodies for safety-related design changes. Nurses need to continue to develop their professional influence by using a multidisciplinary approach to injury prevention. This approach should include health professionals and representatives from the community, the legal profession, law enforcement, regulatory agencies, and both engineers and manufacturers. PMID- 1883582 TI - Head injuries in children. AB - Even though head injury in children is a major health problem facing our nation today, major advances have occurred in our understanding of the epidemiology, pathophysiology, symptomatology, and outcome of these patients. Basic scientists have also contributed to this body of knowledge by demonstrating some unique characteristics of the immature CNS and how it responds to injury. Recent evidence shows that overall mortality and morbidity associated with head injury is declining. Because most pediatric head injuries are nonoperable, it is believed that aggressive medical management to control ICP and prevent secondary injury is responsible for improved outcome. Public education, coupled with legislative support, should prove to be of further benefit. PMID- 1883581 TI - Initial assessment and stabilization of the critically injured child. AB - The care that the child receives during the initial resuscitation and stabilization of a life-threatening injury makes a critical difference in long term outcome. Children who die as a result of a traumatic injury usually do so because of airway compromise, irreparable CNS injury, or bleeding. Hypoxia is the final common event by which these three kill children. If hypoxia is prevented or recognized and treated early, its effects can be reversed before they become permanent. The potential for a good outcome is maximized by expert nursing care for the critically injured child. Expert nursing care includes rapid and accurate assessment and interventions during both the primary and secondary surveys. Knowledge of the anatomic and physiologic differences between children and adults guides the nurse in holistic care of pediatric trauma victims; the nurse must also understand and address the emotional needs of the patients and their families. PMID- 1883583 TI - Thoracic trauma in children. AB - Thoracic trauma is usually accompanied by other body system injury, most frequently head and skeletal injury. Developmental changes throughout childhood make the consequences of such injuries more severe, as children develop respiratory and circulatory compromise quickly. Blunt trauma predominates in pediatric thoracic trauma. Trauma to the thoracic cavity may involve fractures of the ribs or injuries where the ribs remain intact. Trauma involving the pleural space affects ventilation that may evolve into circulatory failure if not addressed promptly. Pulmonary contusion is among the most frequent and most fatal of thoracic injuries. Rupture of the tracheobronchial tree, esophagus, or diaphragm may have both short- and long-term consequences. Trauma to the heart and/or great vessels may be fatal at the scene of the accident, in the emergency department, or in the intensive care unit. Pain management is an essential part of caring for children with thoracic injury. A variety of methods have become available within the past several years that promote better pain relief and shorter recovery periods with less side effects. Nursing care of the child with PCA, epidural analgesia, or intercostal nerve blocks requires specific knowledge and assessment skills. Nonpharmacologic methods of pain relief may be used as an adjunct to pharmacologic methods. PMID- 1883584 TI - Abdominal and genitourinary trauma in children. AB - Children, especially multitrauma victims, are at significant risk for abdominal and GU trauma. Frequently, external indicators of trauma to these systems may be subtle or nonspecific. Expert assessment skills and a knowledge of potential injuries are required. Nonoperative management of these injuries is frequently the treatment of choice, requiring the nurse to understand the type of injury sustained, as well as potential complications of the injury. The nurse is often the first to detect subtle signs of deterioration in the child's condition and must be able to intervene appropriately to promote optimal outcomes for the child. The families of children who sustain abdominal or GU trauma have special teaching needs related to inhospital or home management, as well as long-term outcomes of the injury. It is the responsibility of the nurse to identify and address these needs in a timely fashion to promote optimal outcomes as well as appropriate development for the child. PMID- 1883585 TI - Musculoskeletal trauma in children. AB - Musculoskeletal injuries are common in pediatric trauma victims and may result in extensive surgical intervention and long-term hospitalization. Rapid healing rates in children enhance the prognosis for children with musculoskeletal injuries and may decrease the rate of morbidity from nonunion, infection, and other complications. Nursing interventions to prevent complications and promote healing can be instrumental in decreasing the length of hospitalization, and psychosocial support may be crucial in helping the child cope with the changes associated with major musculoskeletal injuries. PMID- 1883586 TI - Burn injuries in children. AB - The overall outcome for every patient is to attain the maximum level of physical and psychosocial functioning possible within their capacity. This is individualized and impacted by the severity of injury, interventions, and subsequent outcomes along the critical path to recovery. Identification of issues, whether physical or psychosocial, in a timely manner and the development of an individualized plan of care maximize the quality of care each patient receives. As the health care giver in most frequent contact with the patient and family, the nurse must serve as the coordinator of all ancillary services and the plan of care. PMID- 1883587 TI - Children, violence, and intentional injuries. AB - The statistics of violence against children have generated a growing concern about the need to address the problem more aggressively. Homicide, suicide, and child maltreatment are leading causes of mortality in the child and adolescent population; the need to develop strategies to reduce such injuries, therefore, is obvious and urgent. Nurses and other health care professionals are in an ideal position to address this need. They can do so by providing guidance to the general public about how to manage this childhood dilemma. The control of childhood violence must become a national priority; only then will it no longer be a leading cause of mortality and morbidity in children. PMID- 1883589 TI - Vascular disease. PMID- 1883590 TI - Assessment of peripheral arterial occlusive disease. AB - Many older patients in critical care settings have significant arterial disease, so the assessment of peripheral circulation may be important in their management. A great deal of information can be gained through the physical examination, which can be supplemented by the use of the Doppler velocity detector. This device should be used to obtain quantitative pressure measurements. Special consideration must be given to evaluation early in the postoperative period. PMID- 1883588 TI - Complications of pediatric trauma. AB - MSOF is a life-threatening complication of trauma. The body is a dynamic interrelated group of systems that work together efficiently. Changes in one system generally have a widespread impact, and soon the entire system is changed. In children with MSOF, the normal equilibrium that is maintained between organ systems does not exist. Generalized disruption of organ functions occur, and the body attempts to compensate and regain its homeostasis. This activity will often benefit certain organs and harm others. If the disruption continues and compensation fails, organ dysfunction occurs and general chaos reigns. Medical and nursing interventions are directed toward supporting individual organ systems before failure occurs. Attempts to provide this support for one system can cause adverse effects to occur in other systems. Although this is a potential result of medical and nursing interventions, often there is no other choice. It is essential that nurses be aware of the systemic consequences of these interventions and carefully evaluate them. Although overall mortality rates are high, children have a better chance for survival than adults. Expert nursing assessments, interventions, and evaluations are essential to maximize this outcome. More research in the area of MSOF in children is necessary, with specific attention to nursing management and the effect on patient outcome. PMID- 1883591 TI - Carotid endarterectomy: a review. AB - The carotid endarterectomy procedure has provided an invaluable option in the management of patients with symptomatic atherosclerotic carotid artery disease. The criteria for surgical interventions vary from different institutions as well as the mortality and morbidity, but, for a select patient population, it is a viable alternative to conservative medical management. PMID- 1883592 TI - Renal artery occlusive disease. AB - Renal artery occlusive disease, from either atherosclerosis or fibrous dysplasia, may cause hypertension or renal insufficiency. Hypertension results from increased activity of the renin-angiotensin-aldosterone system. There are several ways to evaluate this system as well as several pharmacologic agents that will intervene and modulate the hypertension that results. Percutaneous transluminal angioplasty or surgical revascularization will be necessary in some patients to control blood pressure or improve renal function. Successful evaluation and treatment of these patients are based on clinical experience, an understanding of the natural history of the various disease processes involved, and a comprehensive team approach. PMID- 1883593 TI - Wound healing and peripheral vascular disease. AB - Patients who are hospitalized in the intensive care unit with peripheral vascular disease are at a higher risk for developing complications. The impaired wound healing of this patient population compounds the initial presenting pathology. It is the prudent critical care nurse that realizes this and incorporates this into a plan of care for the patient. Postoperative interventions should be aimed at preserving blood flow and tissue oxygen perfusion and maintaining nutritional requirements to achieve adequate collagen synthesis, angiogenesis, and the prevention of infection. PMID- 1883594 TI - Reperfusion injury. AB - The paradigm of reperfusion is one that will test the skills of the critical care practitioner. This syndrome has been implicated in many of the disorders commonly encountered in the intensive care unit. As research continues and more knowledge is gained into the evolution of this process, many of the complications caused by this affliction will be eliminated. In the interim, understanding of the pathophysiology and the components of this syndrome will assist in providing quality care for the patient unfortunate enough to have encountered this potentially devastating malady. PMID- 1883595 TI - Trends in endovascular surgery. AB - Endovascular surgery is currently in its infancy. Much work is necessary before its full potential can be realized. Initial enthusiasm has appropriately turned into more sober, realistic cautiousness. This review summarizes experiences with angioscopy, IU, PTA, laser angioplasty, atherectomy, and stent placement. Solving the restenosis problem following endovascular interventions could significantly broaden the applications of endovascular surgery. The nursing challenges brought by this new field are not different from those of traditional vascular surgery and catheterization. Keeping up with the new technology as it quickly evolves and documenting clinical effectiveness probably require an endovascular nurse specialist in a center planning to do a great deal of procedures. PMID- 1883596 TI - Culpability and pain management/control in peripheral vascular disease using the ethics of principles and care. AB - The purposes of this article were to provide insight into the process of ethics and ethical inquiry and to explore the ethical issues of culpability and pain management/control. Critical care nurses who currently care for vascular patients identified these issues as occurring frequently in their practice. Authors in critical care nursing generally have limited the process of ethical inquiry to a theoretical framework built around an ethic of principles. The message many critical care nurses heard was that this one type of theoretical ethical framework was the totality of ethics. The application of these principles was ethical inquiry. For some nurses, the ethic of principles is sufficient. For others, an ethic of principles is either incomplete or foreign. This second group of nurses may believe that they have no moral voice if the language of ethics is only the language of principles. The language of principles, however, is not the only theoretical framework available. There is also the ethic of care, and ethical inquiry can include the application of that framework. Indeed, the language of the ethic of care may give a voice to nurses who previously felt morally mute. In fact, these two theoretical frameworks are not the only frameworks available to nurses. There is also virtue ethics, a framework not discussed in this article. A multiplicity of ethical frameworks is available for nurses to use in analyzing their professional and personal dilemmas. Recognizing that multiplicity, nurses can analyze their ethical dilemmas more comprehensively and effectively. Applying differing ethical frameworks can result in the same conclusions. This was the case for the issue of culpability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883597 TI - Comparative evaluation of lisuride and terguride, ergot alkaloid derivatives, on the field-stimulated vas deferens of mouse. AB - The ergot alkaloid derivatives, lisuride (LIS) and terguride (TDHL), known to interact with central dopamine receptors as agonist and partial agonist, respectively, were studied on the field-stimulated mouse vas deferens, where recently the existence of presynaptic dopamine receptors has been evidenced. LIS was a competitive antagonist at prejunctional alpha 2 and DA1 receptors situated on the sympathetic nerve terminals of the mouse, with a pA2 value of 9.2 and 9.1, respectively. LIS was also able to antagonize the effects of LY 171555, selective DA2 agonist, but the type of interaction cannot be conceptualized in terms of competitive antagonism. Likewise, the type of interaction of TDHL with dopaminergic and adrenergic agonist-activated sites is not suggestive of a competitive antagonism. Based on these results, it seems that central and peripheral pharmacologic profiles of LIS and TDHL cannot be overlapped, LIS being a potent DA1- and alpha 2-antagonist with a high degree of specifity for these receptors. PMID- 1883598 TI - Effects of muscarinic receptor agonists and antagonists on dopamine-mediated behavioural paradigms. AB - The effects of some muscarinic M1 and M2 receptor agonists and antagonists on two dopamine-mediated behavioural paradigms, namely post-swim grooming response and apormorphine-induced climbing behaviour, was investigated in mice. The M1 agonists and M2 receptor antagonists attenuated both paradigms, whereas the M1 receptor antagonists and M2 receptor agonists facilitated both behaviours. However, carbachol and physostigmine, exhibited a similar dose-dependent dual effect with the lower doses augmenting and the higher doses inhibiting both the behaviours, suggesting that the M2 agonist receptor specificity is lost on dose increment. The findings indicate that the central cholinergic muscarinic heteroreceptors, like the other muscarinic receptors, are functionally divisible into M1 and M2 receptor subtypes in their modulation of dopaminergic activity. PMID- 1883599 TI - Optical immunosensing systems--meeting the market needs. AB - Optical immunosensors and sensing systems are biosensors which produce a quantitative measure of the amount of antibody, antigen or hapten present in a complex sample such as serum or whole blood. The market needs for such devices and their associated instrumentation are reviewed. A brief history of the development of optical immunosensors is presented and the performance of the most well-developed optical immunosensors for meeting these market needs is reviewed. One device, the fluorescent capillary fill device (FCFD) is reviewed in detail with respect to it fulfilling the market needs for an optical immunosensor. Areas for the future development of such sensing systems are also discussed. PMID- 1883600 TI - An assay for human chorionic gonadotrophin using the capillary fill immunosensor. AB - Recently there has been much research effort directed towards the development of immunosensors. Optical technologies are currently proving very attractive for the construction of such sensors. The fluorescence capillary fill device (FCFD) has been designed to fulfil these needs. The development of an assay for human chorionic gonadotrophin (hCG) in the FCFD for a variety of body fluids (whole blood, serum, urine and saliva) demonstrates the versatility and assay performance of the device. PMID- 1883601 TI - Sensitivity enhancement of optical immunosensors by the use of a surface plasmon resonance fluoroimmunoassay. AB - Optical immunosensors employing evanescent wave techniques have the potential to address the requirements of the 'alternative site' market; however, this potential has yet to be realised. The development of 'direct' sensors, such as those using surface plasmon resonance (SPR), has been hampered by problems of non specific binding and poor sensitivity to small molecules. 'Indirect' sensors (for example, those employing a fluorescently labelled reagent) overcome many of the problems of direct sensors but require more sophisticated instrumentation because of the low light levels detected. In an attempt to combine the best features of the two techniques, an indirect SPR fluoroimmunoassay (SPRF) technique has been investigated. The surface field intensity enhancement produced by SPR is used to boost the emission from a fluorescently labelled immunoassay complex at a metal surface. The potential of the method is demonstrated by assaying for human Chorionic Gonadotrophin (hCG) in serum. Enhanced sensitivity over conventional total internal reflection fluorescence (TIRF) and SPR techniques was achieved. PMID- 1883603 TI - Flow injection immunoanalysis (FIIA)--a new immunoassay format for the determination of pesticides in water. AB - This paper presents the development of a new heterogeneous enzyme immunoassay format for the detection of pesticides. It uses the technique of a flow injection system and is named flow injection immunoanalysis (FIIA). Results are demonstrated for the measurements of the herbicide atrazine, which belongs to the triazines, and the potential of this method compared with another immunoassay format (ELISA) is discussed. PMID- 1883602 TI - Output grating couplers on planar optical waveguides as direct immunosensors. AB - We demonstrated the feasibility of using integrated optical output grating couplers in direct immunosensing. We monitored as functions of time, first the adsorption of an antigen (Ag) on the waveguide's surface, and subsequently, the binding of the corresponding antibody (Ab), i.e. the formation of the immuno complex Ag-Ab. The Ag was human immunoglobulin G (h-IgG), and the Ab was rabbit anti-h-IgG. We also studied the adsorption of avidin. The refractive indices nF', thicknesses dF', and surface coverages gamma of the adsorbed adlayers and of the immuno-complex Ag-Ab, respectively, were determined. PMID- 1883604 TI - Determination of glucose diffusion coefficients in biofilms with micro electrodes. AB - A glucose micro-electrode was developed for direct measurements inside biofilms, and applied for the determination of effective diffusion coefficients in a model system of agar beads containing immobilized yeast cells. Two methods were used, one based on concentration gradients present at the liquid/solid interface of an active biofilm under steady-state conditions, the other based on the rate of glucose redistribution in an inactivated biofilm under transient-state conditions. Additional measurements with pH and oxygen micro-electrodes were performed and thus allowed for in-situ correction of the glucose electrode signal. From the micro-electrode measurements in the model system it was concluded that the glucose micro-sensor is a useful tool with which to obtain effective diffusion coefficients in biofilms. PMID- 1883606 TI - Leakage of different retrograde filling materials in wet and dry environments. PMID- 1883605 TI - Electrochemistry and detection of some organic and biological molecules at conducting poly(3-methylthiophene) electrodes. AB - Electrodes modified by the electrodeposition of poly(3-methylthiophene) were used as chemical sensors for some organic and biological molecules of industrial and medicinal interest. The electrochemical behaviors of ferri/ferrocyanide, catechol, ascorbic acid, hydroquinone, dopamine epinephrine, acetaminophen, p aminophenol and NADH were examined by cyclic voltammetry. The results showed that the proposed modified surface catalyzes the oxidation of these compounds. Differential pulse and square wave techniques were used for the analysis of binary mixture of ascorbic acid with catechol, NADH, dopamine and p-aminophenol. Voltammetric peak resolution was also demonstrated for a ternary mixture of ascorbic acid, catechol and p-aminophenol. Polymer coated electrode was also used in an amperometric detector for flow injection analysis of most of the aforementioned compounds. The responses of the polymer electrode were 4-10 times larger as compared to those of platinum. The modified electrode displayed excellent response stability for successive injections and detection limits were 10 ppb for catechol, dopamine, epinephrine, NADH and p-aminophenol, 1 ppb for acetaminophen and 100 ppb for ascorbic acid. Voltammetric peak positions were affected by the nature of the electrolyte and its pH. Also, film thicknesses were shown to be a factor affecting both the current magnitudes and oxidation peak potential of NADH. PMID- 1883607 TI - The scanning potential microscope: An instrument to image micro-corrosion processes on metallic biomaterials surfaces. PMID- 1883609 TI - Effect of particle configuration on properties of Pd containing dental amalgam. PMID- 1883608 TI - Metal release from low-melting ternary titanium alloys. PMID- 1883611 TI - Effects of two variables on bonding strength. PMID- 1883610 TI - Castability of low-melting ternary titanium alloys. PMID- 1883612 TI - Bonding between visible light-curing and self-curing provisional restorative materials. PMID- 1883613 TI - Transgenic approaches to modification of cell and tissue function. AB - The past 18 months have seen rapid advances in the use of transgenic techniques for elucidating cellular mechanisms. The modification of gene, cellular and tissue function has been enhanced by developments in the use of antisense and ribozyme constructs, and by improvements in strategies for cell ablation and homologous recombination. PMID- 1883614 TI - Calcium regulation and homeostasis. AB - The use of techniques to visualize the stimulus-induced changes in [Ca2+]i that occur at the single cell level has revealed that intracellular Ca2+ signals can be remarkably organized in space (waves), as well as in time (oscillations). New insights are beginning to emerge into how these complex Ca2+ signals may be generated, and into how Ca2+ signals may be transmitted from cell to cell. PMID- 1883615 TI - Cellular aging and senescence. AB - Differentiated eukaryotic cells have only a finite capacity for cell division. This limitation is thought to be a cellular manifestation of organismal aging, and a restraint to tumor progression. The molecular basis for cellular senescence is not known, but a molecular framework for understanding this phenomenon has recently been established. PMID- 1883616 TI - Control of the bacterial cell cycle. AB - New insights into the control of DNA replication through growth, hemimethylated DNA and DnaA protein have been described. Fundamental shifts in thinking have resulted in the identification of new cell cycle genes with potential roles in initiation of DNA replication, chromosomal segregation and division. Excitingly, this trend may also narrow the apparent differences between the prokaryotic and eukaryotic cell cycles. PMID- 1883617 TI - From fungi to flies: pattern and form in the cell cycle. AB - This review shows how, in some lower eukaryotes, recent studies have made important connections between cell cycle control processes and complex events such as organelle positioning and the differentiation of cells and tissues. PMID- 1883618 TI - Spatial aspects of cytokinesis in plant cells. AB - Plant cytokinesis in a particular orientation and location can be viewed as having several component stages, often beginning with the establishment of division polarity before karyokinesis occurs. Improved methods for preserving the in situ distribution of actin microfilaments and observations of individual live cells during treatment with cytoskeleton-disrupting drugs are making it possible to elucidate the roles of microtubules and microfilaments in cytokinesis. Current evidence points to involvement of the cytoskeleton throughout the stages of preparation for, and execution of, cytokinesis in many types of plant cell division. PMID- 1883619 TI - Temporal events regulating the early phases of the mammalian cell cycle. AB - It is proposed that the regulation of the pathways directing mammalian cell cycle progression involves several oncogenes. A summary of what is known about some of these regulatory oncogenes (fos, jun, myc, and Rb-1) and where they might function in the progression of a cell from G0 to G1 and G1 to S is presented. Data on two replication-dependent genes, those encoding histones and thymidine kinase, respectively, are also presented as models for describing transcriptional and post-transcriptional events at the G1-S border. PMID- 1883620 TI - Mitotic control. AB - 1990 has been a year of continued exciting developments in cell cycle control. Progress has occurred in delineating the mechanism of activation of maturation promoting factor during entry into mitosis and the mechanism of cyclin degradation responsible for exit from mitosis. Notable advances have also occurred in our understanding of the dependence of mitotic entry on completion of DNA synthesis. Both genetic and biochemical data link this crucial checkpoint to the function of the cdc25 gene product and the extent of phosphorylation of Tyr15 in cdc2 kinase. PMID- 1883622 TI - Cell multiplication. PMID- 1883621 TI - The complexity of cell proliferation control in mammalian cells. PMID- 1883623 TI - Red blood cell insulin receptors in health and disease. AB - CONTENTS: Structure and characteristics of erythrocyte insulin receptor. Red blood cell age and insulin receptors. Insulin receptors in human disease states. Obesity. Chronic renal failure. Acanthosis nigricans. Miscellaneous disease states. Insulin receptors in children. Insulin receptors in women during pregnancy. Insulin binding and other hormones. Comparison of biosynthetic insulin, pancreatic human insulin and porcine insulin binding to erythrocytes. Effect of exercise on insulin binding to red blood cells of normal human volunteers. Miscellaneous insulin binding studies. Insulin internalization and degradation. Insulin and erythrocyte metabolism. Summary and conclusion. PMID- 1883624 TI - The effect of propane-diols on the intestinal uptake of nutrients and brush border membrane enzymes in the rat. AB - The effect on rats of oral doses (38.66 mM/kg body wt) of propane-1,2-diol (PD) administered daily for 10 (Group 1), 20 (Group 2), and 30 days (Group 3) was investigated. Weight gain was initially retarded (P less than 0.05) in Group 1, but was later reversed and elevated significantly (P less than 0.05) in Groups 2 and 3 as compared with their respective controls receiving an equal volume of saline. PD showed a tendency toward enhancing the activities of various enzymes involved in terminal digestion, with the significant effect exerted in few groups on sucrase (P less than 0.05), lactase (P less than 0.05), and gamma-glutamyl transpeptidase (P less than 0.05) when compared with the respective controls. Absorption of D-glucose, glycine, L-aspartic acid, L-lysine, and calcium was elevated and was especially significant in Groups 2 and 3 (P less than 0.001). The structural integrity of the jejunal surface was retained for the most part. A similar examination of the effects of PD was also carried out in vitro to ascertain whether PD itself or its metabolites are involved in its action. The in vitro effects of propane-1,2-diol were compared with those of the more toxic compound propane-1,3-diol. The former exerted greater inhibitory action on the activities of the disaccharidases. The degree of inhibition was in the order sucrase much greater than lactase greater than maltase. The kinetic data revealed that inhibition by 1,2-diol in native and detergent solubilized sucrase is noncompetitive, with Ki values in the range of 0.35-0.41 M. The two diols did not alter the nutrient transport in the brush border membrane vesicles. The present work on rats indicates that PD may influence the intestinal digestive and absorptive functions in vivo and that this in vivo effect of PD is different from that observed in vitro suggesting that the nutritional and toxicological effect of PD may be mediated by different mechanisms. PMID- 1883625 TI - Influence of heparins on inositol 1,4,5-trisphosphate-induced calcium mobilization in permeabilized human platelets. AB - Heparin has been shown to prevent inositol 1,4,5-trisphosphate (IP3) binding to its receptor and to inhibit IP3-induced calcium mobilization in a variety of cells. Heparin added to whole blood at a concentration of 1 U/ml prevented thrombin-induced secretion of granule contents and irreversible aggregation of platelets. Heparin (2-15 kDa) had no inhibitory effect on IP3-induced calcium mobilization in Fura 2-loaded, saponin (10-15 micrograms/ml)-permeabilized platelets. None of the commercially available heparin preparations can induce inhibition of agonist-induced calcium mobilization in intact platelets because they are not cell permeant. Mild saponin treatment makes the membrane permeable to IP3, but restricts the action of heparins. Recent observations suggesting heparin's affinity to IP3 binding sites will be of clinical interest if effective cell permeant analogs can be developed. PMID- 1883626 TI - Sandwich enzyme immunoassay for rat transferrin with two monoclonal antibodies and its application. AB - The development of a sandwich enzyme immunoassay for rat transferrin with two monoclonal antibodies is described. Microtiter plates coated with one monoclonal antibody (15C2H3) were used, and captured transferrin was estimated with a horseradish peroxidase-conjugated Fab' fragment of another monoclonal antibody (22A06D2). In this assay, the measurable range is 5-150 ng/ml and the coefficients of variation within and between the assay series are 1.2-5.0 and 3.3 6.0%, respectively. Recovery was 101 +/- 9.7% when purified rat transferrin was added to rat plasma. No cross-reactivity with bovine, human, or mouse transferrin was shown. This assay for rat transferrin is a highly specific, sensitive, and expeditious method which may allow routine analysis of rat transferrin in blood or culture supernatants of rat hepatocytes. PMID- 1883627 TI - Immunochemical analysis of the peroxisomal beta-oxidation enzymes in rat and human heart and skeletal muscle and in skeletal muscle of Zellweger patients. AB - Immunoblot analyses with antibodies against the peroxisomal beta-oxidation enzymes from rat liver showed the presence of these enzymes in rat and human liver and kidney and rat adrenal gland. The bifunctional protein could not be detected in muscle tissues or cultured muscle cells. Acyl-CoA oxidase was detected in rat heart and cultured human muscle cells. 3-Ketoacyl-CoA thiolase was also detected in human and rat heart and skeletal muscle; however, this enzyme was not detectable in skeletal muscle of Zellweger patients, in agreement with the absence of peroxisomal fatty acid oxidation. PMID- 1883628 TI - Effect of coenzyme Q10 on structural alterations in the renal membrane of stroke prone spontaneously hypertensive rats. AB - To test the hypothesis that structural abnormalities exist in the kidney membrane of spontaneously hypertensive rats, we examined the effect of long-term administration of coenzyme Q10 on membrane lipid alterations in the kidney of stroke-prone spontaneously hypertensive rats (SHRSP). As compared with normotensive Wistar-Kyoto rats, renal membrane phospholipids, especially phosphatidylcholine and phosphatidylethanolamine, decreased and renal phospholipase A2 activity was enhanced with age in untreated SHRSP. Treatment with coenzyme Q10 attenuated the elevation of blood pressure, the membranous phospholipid degradation, and the enhanced phospholipase A2 activity. These results suggest that one factor contributing to the progress of hypertension is a structural membrane abnormality that alters the physical and functional properties of the cell membrane, and coenzyme Q10 might protect the renal membrane from damage due to hypertension in SHRSP. PMID- 1883630 TI - Propionate mitochondrial toxicity in liver and skeletal muscle: acyl CoA levels. AB - Propionic acidemia occasionally produces a toxic encephalopathy resembling Reye syndrome, indicating disruption of mitochondrial metabolism. Understanding the mitochondrial effect of propionate might clarify the pathophysiology. Liver mitochondria are inhibited by propionate (5 mM) while muscle mitochondria are not. Preincubation is required to inhibit liver mitochondria, suggesting that propionate is metabolized to propionyl CoA. Liver and skeletal muscle mitochondria incubated with [1-14C]propionate contain similar quantities of matrix isotope and release comparable [14C]CO2. However, only liver mitochondria accumulated significant propionyl CoA, which was largely (68%) synthesized from propionate. Carnitine reduced the level of liver matrix propionyl CoA. Inhibition of respiratory control ratios by propionate correlated with propionyl CoA levels. These results support the hypothesis that acyl CoA esters are toxic and that carnitine exerts its protective effect by converting acyl CoA esters to acylcarnitine esters. PMID- 1883629 TI - Assay of 3-hydroxybutyrate in the picomolar range. AB - A radioisotopic procedure for the assay of 3-hydroxybutyrate is presented. It is based on the measurement of NADH, generated in the 3-hydroxybutyrate dehydrogenase reaction, through the conversion of 2-[U-14C]ketoglutarate to 14C labeled L-glutamate in the presence of beef liver glutamate dehydrogenase. The assay is linear in the range of 2.5 to 20.0 pmole/sample and about 100-times more sensitive than previous methods. The procedure proved useful for the measurement of 3-hydroxybutyrate in liver samples not exceeding 25 micrograms wet weight. PMID- 1883631 TI - Modulation of elastase-like activity in fibroblasts stimulated with elastin peptides. AB - Elastin-derived peptides, kappa-elastin, prepared by chemical degradation of insoluble elastin from bovine ligamentum nuchae, were shown to increase the elastase-like activity in the culture medium and cell fractions in fibroblasts. Preincubation of cells with nifedipine (calcium channel blocker) and trifluoperazine (calmodulin antagonist) induced a decrease in the activities of the enzyme under study. These data suggest the possibility of pharmacological modulation of the biological effects induced by elastin-derived peptides. PMID- 1883632 TI - Heterogeneity of human liver alanine aminotransferase due to sulfhydryl groups oxidation. AB - The cytosolic isoenzyme of human liver alanine aminotransferase exhibited a progressive change in its chromatographic behavior on DEAE-Sepharose when partially purified preparations were stored for up to 8 days at 4 degrees C. This change was characterized by the appearance of an additional chromatographic variant and was avoided by addition of 2-mercaptoethanol. The experimental evidence presented indicates that the progressive oxidation of free sulfhydryl groups of the enzyme is responsible for the charge modifications and heterogeneity observed. PMID- 1883633 TI - Distribution of histo-blood group antigens in cervical and uterine endometrium. AB - Cell surface carbohydrates serve as differentiation and developmental markers characteristic of different cell and tissue types. Expression of these carbohydrate antigens is often significantly altered in tumors particularly in those arising from epithelial tissues. Analysis of the expression of cell surface carbohydrates in normal endometrium has shown that this glycosylation is hormonally influenced. Change in expression of carbohydrates in malignant tissue should therefore be evaluated against this normal fluctuation. In normal cervical uterine epithelium the result shows that the glycosylation of metaplastic squamous cells is different from that of original squamous cells indicating that the regulation and differentiation of the epithelium in the transformation zone is different from that of the original squamous epithelium. This variation in expression of carbohydrates seen in the metaplastic epithelium may be of importance for the development of carcinomas in this area. PMID- 1883635 TI - Malignant giant cell tumour of the uterus. AB - Two rare cases of malignant giant cell tumours of the uterus in pure heterologous form are presented. Light microscopy showed numerous osteoclast-like cells in a background of spindle cells. Immunohistochemistry demonstrated Vimentin, Actin, alpha-1-antitrypsin and LCA in the latter, and Vimentin, alpha-1-antitrypsin and LCA in the giant cells while tartrate resistant acid phosphatase reactivity was demonstrated in both mononuclear cells and giant cells. Electron microscopy did not reveal smooth muscle or epithelial differentiation. The findings suggest a common origin of malignant giant cell tumours and malignant fibrous histiocytomas. PMID- 1883636 TI - Glassy cell carcinoma of the uterine cervix. AB - Eighteen cases of glassy cell carcinoma of the uterine cervix are presented. Glassy cell carcinoma is an uncommon, aggressive type of adenosquamous carcinoma of the uterine cervix, which is considered to originate from the subcylindrical reserve cells of the cervix. The patients with this tumor are younger than those with other types of invasive carcinoma of the uterine cervix, and all but three in this study were 34 years or younger. The tumors were frequently large, endophytic and growing rapidly. Metastases were found on presentation in two cases. The larger tumors did not respond well to treatment. Seven of the patients died within 20 month of diagnosis. Histologically glassy cell carcinoma is composed of nests of large cells with ground glass cytoplasm and large vesicular nuclei with prominent nucleoli. There is marked cellular and nuclear pleomorphism and tumor giant cells are frequently seen. Mitotic activity is brisk. Infiltration by eosinophils and plasma cells with admixture of lymphocytes is a characteristic feature. Focal squamous or glandular differentiation may be seen. Ultrastructural studies showed a wide spectrum of appearances. These findings lend further support to the view that glassy cell carcinoma is a distinctive type of poorly differentiated adenosquamous carcinoma of the uterine cervix. PMID- 1883634 TI - DNA flow cytometry in uterine endometrial carcinoma. AB - The DNA content was investigated by means of flow cytometry in frozen tumor specimens from 33 patients with uterine endometrial carcinoma. The association was tested between ploidy and S-phase fraction on one hand and clinico pathological parameters on the other. Aneuploidy appeared in 15 (45%) of the patients, and the average S-phase fraction was 0.18 (0.04-0.34). There was a highly significant correlation between DNA-Index (DI) and histologic differentiation (p = 0.01) and a less significant correlation between DI and estrogen receptor content (p = 0.04). DNA ploidy measured by flow cytometry is a highly reproducible parameter that in addition to routine histopathological examination may provide useful information. Further studies are needed to establish the prognostic importance of the flow cytometric parameters. PMID- 1883637 TI - Portal hypertension without liver cirrhosis in renal transplant recipients. AB - A rare syndrome of portal hypertension with esophageal varices but without evidence of cirrhosis in the liver biopsy was seen in 3 patients in a series of 1000 renal allotransplant recipients immunosuppressed with azathioprine and prednisone. The liver disease began 3-6 years after transplantation with abnormal liver function tests and esophageal varices with bleeding episodes. One patient had also ascites. Liver biopsy at the beginning of liver disease showed in one patient normal structure which eventually developed to slight diffuse fibrosis and nodular hyperplasia. One patient had diffuse fibrosis, and the third patient had strong sinusoidal engorgement with nodular hyperplasia, later on developing to cirrhosis. One patient is still alive and well, the two others died from liver insufficiency. 39 cases of non-cirrhotic portal hypertension in renal transplant recipients and histologic evidence of peliosis, sinusoidal dilatation, nodular hyperplasia or hepatic veno-occlusive disease have been identified in the literature. The cause of this disease is presumably azathioprine, but its rarity shows that it must depend also on other factors. PMID- 1883638 TI - Tumor-like lesions of the secondary mullerian system. Immunohistochemical investigations and differential diagnosis. AB - Even postnatally, the female peritoneum (mesothelium and submesothelial mesenchyme) has a potential for differentiation (secondary Mullerian system) similar to that of the embryonic coelom epithelium. This potential is manifested in some cases under an evident hormonal stimulus, and in other cases without an apparent cause. The functional similarity of the differentiation products of the secondary Mullerian system with structures of the primary Mullerian system is underscored by their common antigens which have been detected immunohistologically, including the expression of steroid receptors. Of the lesions of the secondary Mullerian system, in particular endosalpingiosis is of special importance because of its frequency and the in some cases grave therapeutic consequences. Atypical distinguished even using immunohistological techniques. PMID- 1883639 TI - The calcifying epithelial odontogenic tumor. A review of recent literature and report of a case. AB - The calcifying epithelial odontogenic tumor (CEOT) was described as an entity by Pindborg in 1955. In 1976 a review of the world literature comprising 113 cases was published. Since then, several studies concerned with pathological aspects of this tumor have appeared. Many of these studies have focused on the nature of the amyloid-like material present in CEOT. In this paper a new case is presented and the literature after 1976 is reviewed with respect to histopathological aspects of CEOT. PMID- 1883640 TI - Transferrin receptor expression in normal and iron overloaded liver. AB - Hepatocytes take up transferrin-bound iron by two mechanisms. One pathway consists in the binding of transferrin to high affinity receptor sites. This process results in receptor-mediated endocytosis and is highly efficient and saturable. The other mechanism involves low affinity, non-specific and non saturable internalization of transferrin-bound iron, probably through pinocytosis, adsorptive endocytosis or low affinity binding sites. At low transferrin saturation, the first mechanism is quantitatively most important, at high transferrin saturation the latter mechanism becomes more significant. A mechanism whereby transferrin-bound iron is not endocytosed but reduced at and translocated through the plasma membrane has also been invoked and challenges the concept of (receptor-mediated) endocytosis of transferrin. However, this hypothesis remains to be confirmed. PMID- 1883641 TI - In honour of Hemming E. Poulsen. PMID- 1883642 TI - Hemming Engelund Poulsen 1921-26 August-1991. PMID- 1883643 TI - Cells with neuroendocrine features in regenerating human liver. AB - Regeneration of liver tissue in man after submassive necrosis is reflected by replicating features in hepatocytes, and by a remarkably increased number of bile duct structures that are thought to transdifferentiate into true functioning hepatocytes. Similar to the bile ductule-related "oval cells" in rats, human bile ductular cells may therefore serve as "facultative stem cells" that become activated when hepatocyte regeneration is insufficient or inhibited. Our recent demonstration of neuroendocrine features in proliferating bile ductules in cholestatic liver disease prompted us to perform a similar immunohistochemical and electron microscopical study on regenerating human liver tissue after submassive liver necrosis. In the earliest stages of regeneration, bile ductular cells and small, singular cells in the periportal area expressed chromogranin-A and contained dense-cored, secretory granules. It is tempting to speculate that the scattered singular cells represent the human equivalent of the bipotential progenitor cells in the rat. In later stages of regeneration, these singular cells were no longer evident, suggesting their differentiation into other cell types. In these cases, neuro-endocrine cells corresponded to proliferating bile ductules and to scattered, typical hepatocytes, located near portal tracts and in regenerating nodules. In all cases, proliferating bile ductules displayed the neural cell adhesion molecule (NCAM). These data further support our hypothesis that the substance(s) produced in the dense cored secretory granules may play a role in the growth and/or differentiation of liver cells through an autocrine and or paracrine pathway. PMID- 1883644 TI - The spectrum of alcohol induced liver disease. Histological features. AB - Alcohol may induce a variety of changes in the liver. None of the features are diagnostic, but some are relatively specific. Usually the simultaneous occurrence of one or more non-specific lesions in combination with other more specific changes leads to the correct diagnosis of alcoholic liver disease. PMID- 1883645 TI - Dendritic cells and the liver. AB - In comparison to other cells involved in the hepatic immune response, dendritic cells in human liver tissue have received remarkably little attention. In view of their presence in normal liver, and their multiple immunological functions, it can be anticipated that dendritic cells are involved in viral, autoimmune and rejection immune responses of the human liver. PMID- 1883647 TI - The effect of dexamethasone upon platelets and neutrophils of preterm infants with chronic lung disease. AB - The effect of a 21-day (reducing dose) course of dexamethasone upon platelet numbers, neutrophil numbers and neutrophil morphology in ventilator-dependent preterm infants with chronic lung disease is reported. Forty-one infants, who were sepsis-free throughout the treatment period, received 46 courses of dexamethasone. In these infants the circulating platelet count increased significantly from 235 +/- 157 to 476 +/- 208 X 10(9)/L. Both total neutrophil numbers (7.94 +/- 7.16 to 19.56 +/- 12.40 X 10(9)/L) and immature neutrophil numbers (1.19 +/- 1.22 to 2.68 +/- 2.58 X 10(9)/L) also showed a significant increase reaching a peak on day 7 of treatment and decreasing thereafter. The immature:total (I:T) neutrophil ratio remained essentially unchanged. Eight other infants who developed serious sepsis during the treatment period showed a fall in both platelets (293 +/- 236 to 140 +/- 170 X 10(9)/L) and total neutrophil numbers (18.61 +/- 10.83 to 15.76 +/- 10.53 X 10(9)/L), together with an increase in immature neutrophils (2.30 +/- 2.80 to 8.22 +/- 13.91 X 10(9)/L) and consequent increase in I:T ratio. PMID- 1883646 TI - A reappraisal of Poulsen's disease (hepatic zone 1 sinusoidal dilatation). AB - The possible cause and pathogenesis of this disease are reviewed. The condition is rare, and there are only few reports which throw some light on this remarkable morphology. It is hypothesized that metabolic zonation in the functional liver acinus may be the basis of these changes, but lack of experimental and clinical studies still makes it enigmatic. PMID- 1883648 TI - Three cases of congenital adrenal hypoplasia: a cause of salt-wasting and mortality in the neonatal period. AB - Three infants with congenital adrenal hypoplasia are described. The two surviving infants were detected and successfully treated in the neonatal period due to a suggestive family history (Case 1) and antenatal maternal oestriol screening (Case 2). The modes of inheritance, diverse clinical presentation, associated conditions, diagnostic work-up and pathology of congenital adrenal hypoplasia in these three infants is discussed. PMID- 1883649 TI - Haemophilus influenzae septicaemia in the neonate: report of two cases and review of the English literature. AB - Two neonates with early onset respiratory illness were found to have Haemophilus influenzae septicaemia. One of them died. A review of the English literature showed that Haemophilus influenzae septicaemia is increasing in incidence. Almost all cases presented with respiratory distress in the first 2 days. Other associated features included meningitis, arthritis, conjunctivitis and cellulitis. The mortality, which averaged 52%, was high, especially in premature babies. The septicaemia was caused by ascending infection from the colonized maternal birth canal, and most cases were caused by nontypable strains of Haemophilus influenzae. Because of the occurrence of ampicillin or chloramphenicol resistance, a third generation cephalosporin is the treatment of choice for known cases of serious infection. PMID- 1883650 TI - Two unusual tumours of the gastrointestinal tract in a patient with tuberous sclerosis. AB - A 16 year old girl with an established diagnosis of tuberous sclerosis presented with a 1 year history of swelling of the left cheek. A 2 cm diameter tumour was excised which showed histological features of a solid variant of a minor salivary gland basal cell adenoma. One year later during laparotomy and excision of multiple renal angiomyolipomas, a 5 cm diameter subserosal tumour was found at the hepatic flexure of the colon. Examination of biopsy material revealed a leiomyoma. This case is presented to demonstrate two tumours that have not to the authors' knowledge been previously described in a young patient with tuberous sclerosis. Although the association may be coincidental, these tumours could represent two rare associations of tuberous sclerosis. PMID- 1883651 TI - It's time: the future of school health services in Australia. PMID- 1883652 TI - The growing role of fetal echocardiography. PMID- 1883653 TI - The amniotic band syndrome. PMID- 1883654 TI - Depression in mothers and behaviour problems with their preschool children. AB - A follow-up study of 224 families of a birth cohort of 272 families in a multi ethnic poor socio-economic municipality in Melbourne when the children were 4 years old showed that 27% of the mothers were depressed. There was no difference in the depression rate between Australian-born and immigrant mothers, a finding in marked contrast to the first year of the study when the depression rate was significantly higher in those immigrant mothers who had been in Australia for less than 3 years, were unable to speak English and who did not have an extended family or close friends. Depression in this group of mothers was attributed to resettlement problems, which over a period of three years had ameliorated. At 4 years the most important factor associated with depression in both Australian born and immigrant mothers was the quality of marital relationships. Lack of an intimate support relationship made mothers more vulnerable to the stresses of child care and rearing, home-making and life events. In Australian-born mothers only, another significant factor in vulnerability to depression, was their early childhood experiences of being reared in a disruptive home or in an institution and of being unwanted. In immigrant mothers, but not in Australian-born mothers, life events were significantly correlated with depression. The depressed mothers, both Australian-born and immigrant, perceived their 4 year old children to have significantly more behavioural problems than mothers who were not depressed. PMID- 1883655 TI - Anthropometry and obesity in myelomeningocele. AB - Anthropometric data on 110 myelomeningocele (MMC) subjects in relation to age, sex, level of lesion and ambulation were studied to investigate growth and the occurrence of obesity in MMC. In 52 subjects, indices of obesity were validated against body composition analysis of total body fat (%BF) using body potassium and body water techniques. Most subjects were short and light compared to reference data and became relatively shorter and heavier with age. Overall trunk growth was not affected by the level of lesion, but sitting height was affected by kyphoscoliosis. Arm spans were similar to reference data, but were significantly greater in wheelchair users. Leg length was greatest in those who walked. Body composition data showed excess adipose in many MMC subjects, this tendency increasing with age. When correlated with %BF determined from body composition analysis, common clinical indices of obesity had variable r values (wt/ht2 0.78; wt/sitting ht2 0.77; upper arm fat area 0.75; triceps skinfold 0.74; wt/arm span2 0.68, with the 4 skinfold method correlating best, 0.82). Anthropometric measures, taken with cognizance of level of disability and mobility, can accurately assess body growth and the occurrence of obesity in MMC. The influence of ambulatory activity in promoting normal growth is emphasized. PMID- 1883656 TI - Outcomes of routine school entrant health assessments in Christchurch. AB - The School Entrant Health Assessment (SEHA) programme was established in New Zealand to ensure that every child entering school was assessed by a nurse. This type of service has come under a lot of criticism and so we investigated the scheme in Christchurch, looking at the outcome of the physical examination. We did not explore the health promotion aspect of the nurses' work. We traced the path of 1281 new entrants. The nurses identified problems in 459 (35.8%) children and nearly half were given further appointments or referred on. However, it was judged that only 21 (1.6%) children might have actually received a significant long-term benefit. We feel that a non-selective approach to school entry health assessments is inefficient. Nevertheless, the opportunity to fully audit the health of new school entrants is most important and could be a valuable opportunity for health promotion. PMID- 1883658 TI - The implications of shifting paradigms. PMID- 1883657 TI - Methadone levels and neonatal withdrawal. AB - The purpose of this study was to observe the effects of methadone exposure in utero, with special reference to maternal and neonatal methadone concentrations and neonatal withdrawal. Two groups of mother-infant pairs were studied. In the first group, serum methadone concentrations were determined in infants at 1, 6 and 24 h after delivery. In the second group, blood was obtained at 24, 48, 72 and 96 h after birth. There was no correlation between neonatal serum levels and the intensity of withdrawal symptoms. There was no relationship between maternal methadone dose at delivery or maternal serum levels and neonatal methadone levels. The results of this study may be complicated by the prenatal exposure of the neonates to other drugs of abuse apart from methadone. PMID- 1883659 TI - The physician's place and role in health care delivery. PMID- 1883660 TI - Preparing the nurse for administration: the changing focus. PMID- 1883662 TI - Quantitative angiography after directional coronary atherectomy. AB - OBJECTIVE: To assess by quantitative analysis the immediate angiographic results of directional coronary atherectomy. To compare the effects of successful atherectomy with those of successful balloon dilatation in a series of patients with matched lesions. DESIGN: Case series. SETTING: Tertiary referral centre. PATIENTS: 62 patients in whom directional coronary atherectomy was attempted between 7 September 1989 and 31 December 1990. INTERVENTIONS: Directional coronary atherectomy. MAIN OUTCOME MEASURES: Increase in minimal luminal diameter of coronary artery segment. RESULTS: Angiographic success on the basis of intention to treat was obtained in 54 patients (87%). In four patients the lesion could not be crossed by the atherectomy device; all four had an uneventful conventional balloon angioplasty. Four of the 58 patients who underwent atherectomy were subsequently referred for coronary bypass surgery because of failure or complications; three of them sustained a transmural infarction. In the successful cases, coronary atherectomy resulted in an increase in the minimal luminal diameter from 1.1 mm to 2.5 mm with a concomitant decrease of the diameter stenosis from 62% to 22%. In the subset of 37 patients in which the changes induced were compared with conventional balloon angioplasty atherectomy increased the minimal luminal diameter more than balloon angioplasty (1.6 v 0.8 mm; p less than 0.0001). Conventional histology showed media or adventitia in 26% of the atherectomy specimens. In hospital complications occurred in six patients who had undergone a successful procedure: two transmural infarctions, two subendocardial infarctions, one transient ischaemia attack, and one death due to delayed rupture of the atherectomised vessel. All patients were clinically evaluated at one and six months. One patient had persisting angina (New York Heart Association class II), one patient sustained a myocardial infarction, one patient underwent a percutaneous transluminal coronary angioplasty for early restenosis, and one patient underwent coronary bypass surgery because of a coronary aneurysm formation. At six months 80% (36/47) of the patients were symptom free. CONCLUSIONS: Coronary atherectomy achieved a better immediate angiographic result than balloon angioplasty; however, in view of the complication rate in this preliminary series, which may be related to a learning curve, a randomised study is needed to show whether this procedure is as safe as a conventional balloon angioplasty. PMID- 1883661 TI - The treatment of primary pulmonary hypertension. PMID- 1883663 TI - Early experience with low speed rotational angioplasty. AB - OBJECTIVE: Preliminary assessment of the efficacy and safety of the low speed rotational angioplasty catheter system (ROTACS). DESIGN: Open prospective trial. SETTING: Department of cardiology in a teaching hospital. PATIENTS: Eleven patients (10 with chronic stable angina and one with acute coronary occlusion after conventional angioplasty) in whom a coronary angiogram showed occlusion or critical stenosis of the coronary artery (right in seven patients, circumflex in two, and left anterior descending in two). The nature or severity of the lesion ruled out conventional coronary angioplasty. INTERVENTIONS: An attempt was made to cross the lesion with a rotating guide wire with a blunt swelling at its tip. Where necessary progress was assessed by simultaneous injection of contrast into both main coronary arteries. MAIN OUTCOME MEASURES: Progress of the ROTACS through the lesion that allowed a guide wire to pass into the distal vessel was regarded as a device specific success. When a guide wire crossed the lesion aided only by the support of the ROTACS without the use of rotation this was counted as a success that was not device specific. Failure to cross the lesion and any associated complications were noted. RESULTS: The ROTACS crossed only two of the 10 chronic lesions (20% device specific success rate); however, the support it provided enabled a guide wire to cross a further two lesions and allowed subsequent successful angioplasty in four of the 10 patients. One of these four patients presented after five months with recurrent angina requiring bypass grafting. The other three were symptom free at follow up seven months after the procedure. In the one patient with acute coronary occlusion the ROTACS was advanced over the guide wire to allow passage of an angioplasty balloon where this had previously proved impossible. An excellent final result was obtained and this patient remains symptom free. Three of the six patients in whom the ROTACS was unsuccessful had coronary artery dissection without sequelae. Three patients required subsequent elective coronary bypass grafting for control of symptoms while the other three remain well on medical treatment. CONCLUSIONS: The ROTACS may extend the range of patients with coronary artery occlusion or critical stenosis who can be treated non-surgically. The low device specific success rate (20%) achieved in this study indicates that it should be compared with other simpler mechanical devices that may be just as effective. PMID- 1883664 TI - Immunoglobulin response to intravenous streptokinase in acute myocardial infarction. AB - OBJECTIVE: To devise assays to assess and follow the specific antibody response in patients treated with streptokinase for acute myocardial infarction. DESIGN: Venous blood samples were collected before treatment with streptokinase started and subsequently at regular intervals over one year. Specific IgG and subclass IgG1 were assessed by an enzyme linked immunosorbent assay. SETTING: Coronary care unit in a general hospital. PATIENTS: 48 patients with acute myocardial infarction: 22 patients had venous blood samples taken at presentation only; serial blood samples were taken from 20 patients who then received thrombolytic therapy with streptokinase and six patients who were unsuitable for thrombolytic therapy. RESULTS: Titres of antibodies to streptokinase were low at presentation in 36 (75%) of the 48 patients. Serial measurements made in 20 patients showed the virtual disappearance of antibody within the first 24 hours. This was followed by a steady increase in the specific IgG1 titre, which peaked at day 14 before gradually declining. Values at one year remained significantly higher than baseline values. There was no evidence of an IgM response in the patients studied. CONCLUSION: Low titres of antibodies to streptokinase were widespread in the population. Antibody was consumed after treatment and the subsequent immunoglobulin rise suggested a secondary immune responses; the recently described neutralising capacity to streptokinase is probably related to this antibody. PMID- 1883665 TI - Predictive value of ventricular arrhythmias for patency of the infarct-related coronary artery after thrombolytic therapy. AB - In animal studies reperfusion of coronary arteries is commonly accompanied by ventricular arrhythmias. It is not certain, however, whether ventricular arrhythmias can be used as a reliable non-invasive marker of reperfusion in humans. Two-channel Holter recordings were obtained from the start of an intravenous infusion of streptokinase until coronary angiography (2.8 (2.7) hours (mean SD)) afterwards) in 57 patients with acute myocardial infarction of less than four hours who were generally not treated with antiarrhythmic drugs. Ventricular arrhythmias occurred in 21 (37%) of the 57 patients: accelerated idioventricular rhythm in 13 patients and non-sustained ventricular tachycardia in 15 patients. Seven patients had both accelerated idioventricular rhythm and non-sustained ventricular tachycardia. Coronary angiography showed a patent infarct-related vessel in 12 (92%) of the 13 patients with accelerated idioventricular rhythm (95% confidence interval 66 to 99%), in 22 (50%) of the 44 patients without accelerated idioventricular rhythm (95% CI 34 to 66%), in 11 (73%) of the 15 patients with non-sustained ventricular tachycardia (95% CI 45 to 92%), and in 23 (55%) (95% CI 39 to 71%) of the 42 patients who did not have non sustained ventricular tachycardia. Seventeen (81%) of the 21 patients with accelerated idioventricular rhythm, or non-sustained ventricular tachycardia, or both, had a patent infarct-related vessel (95% CI 58 to 94%) as did 17 (47%) of the 36 patients with no ventricular arrhythmia (95% CI 29 to 65%). In patients with accelerated idioventricular rhythm after thrombolysis the infarct-related vessel is almost certain to be patent; but the infarct-related coronary artery can still be patent when no arrhythmia is seen. PMID- 1883666 TI - Post-prandial worsening of angina: all due to changes in cardiac output? AB - BACKGROUND: The precise mechanism leading to the post-prandial worsening of angina has yet to be adequately defined. It has been attributed to an increase in double product but is perhaps more likely to be related to an increase in cardiac output after food. This study was designed to evaluate the effects of food on patients' exercise tolerance and compare these with changes in haemodynamic variables. METHODS: 23 patients with chronic stable angina who had post-prandial worsening of their angina were studied. The patients were evaluated on two occasions and at each visit they underwent two symptom limited treadmill exercise tests. They remained fasting on the first visit and were given a 1400 kcal meal 60 minutes before the second exercise test on the second visit. Time to onset of 1 mm ST segment depression, heart rate, systemic arterial blood pressure, and cardiac output were measured at rest and during exercise. RESULTS: There were no differences in any of the variables during the two exercise tests on the day the patients remained fasting. After the meal exercise tolerance fell significantly by 136 seconds and the stage at which 1 mm ST segment depression was first seen was also significantly reduced. Resting cardiac output increased significantly by 0.86 1/min with the patients sitting and by 0.89 1/min standing. The exercise times after food were significantly related to cardiac output even when fasting times were taken into account. Resting heart rate increased significantly by 8.3 beats per minute sitting and 10.4 beats per minute standing. There was little change in blood pressure and no evidence that the double product predicted the post-prandial exercise time. CONCLUSIONS: Worsening of angina was related to the increase in cardiac output after a meal and successful treatment will depend upon the prevention of this increase. PMID- 1883667 TI - Mitral valve repair: a valuable procedure with good long term results even when performed infrequently. AB - OBJECTIVE: To assess the results of mitral valve repair in a series with a low frequency of repair despite a policy to conserve the valve whenever possible. DESIGN: Retrospective review of case notes with clinical and echocardiographic examination of survivors. SETTING: Cardiac surgery unit in a university teaching hospital. PATIENTS: 62 consecutive patients undergoing mitral valve repair by one surgeon between 1979 and 1989. INTERVENTIONS: Mitral valve repair according to the criteria and techniques of Carpentier. MAIN OUTCOME MEASURES: Frequency of repair, operative mortality, actuarial survival, freedom from reoperation and thromboembolism, clinical state, and echocardiographic state. RESULTS: The 62 patients, median age 58 years (interquartile range 51 to 64 years), represent 14% (70% confidence interval 12% to 15%) of the 454 mitral valve operations performed in the study period. Operative mortality was 8% (70% CI 5% to 13%). Actuarial survival was 62% (70% CI 43% to 81%) at nine years. At nine years actuarial freedom from reoperation was 91% (70% CI 79% to 102%) and freedom from thromboembolism 91% (70% CI 80% to 102%). At a median follow up of 33 months (interquartile range 21 to 74 months), 38 of 46 survivors had improved functional state. Of 21 patients who underwent echocardiography one had severe mitral regurgitation and one mitral stenosis. CONCLUSION: Although compared with other reports of mitral valve repair the prevalence of repair was low in this series the results are comparable and justify a positive approach to repair in all patients undergoing mitral valve surgery even if this can only be achieved in a small proportion of patients. PMID- 1883669 TI - Multivariate analysis to simplify the differential diagnosis of broad complex tachycardia. AB - Univariate analysis has identified several criteria that aid the differential diagnosis of broad complex tachycardia. In this study of 102 consecutive patients multivariate analysis was performed to identify which of 15 clinical and 11 electrocardiographic variables were independent predictors of ventricular tachycardia. These were shown to be a history of myocardial infarction, the QRS waveforms in leads aVF and V1, and a change in axis from sinus rhythm to tachycardia of more than 40 degrees. If none of the criteria was met, the diagnosis was almost certainly supraventricular tachycardia. If one criterion was met the diagnosis was probably supraventricular tachycardia. If two criteria were met then the diagnosis was probably ventricular tachycardia. If three or four criteria were met, the diagnosis was almost certainly ventricular tachycardia. The predictive accuracy was 93%. This was increased to 95% by including two other criteria--definite independent P wave activity and ventricular extrasystoles with the same QRS configuration as that in tachycardia. These criteria were not included in the multivariate analysis because though they were 100% specific they were seldom seen. These four criteria can be used as simple rules in determining the origin of a broad complex tachycardia. PMID- 1883668 TI - Cardiac function after surgery for subaortic stenosis: non-invasive assessment of left ventricular performance. AB - OBJECTIVE: To examine left ventricular function after surgical resection of subaortic stenosis during childhood. DESIGN: Left ventricular performance was measured non-invasively in all patients who responded to an invitation for formal assessment. SETTING: Outpatient study, tertiary referral centre. PATIENTS: Twenty three (12 male and 11 female) patients (age range 3 to 31 years) of 43 consecutive patients with fixed subaortic stenosis undergoing surgical resection between 1975 and 1989 reattended for formal assessment 16 months to 15 years (median 4 years 4 months) after operation. MAIN OUTCOME MEASURES: Left ventricular dimension, left ventricular wall thickness, left ventricular Doppler inflow velocities, and left ventricular diastolic pressure (measured from apexcardiograms). Results were compared with those in controls individually matched for age and sex. RESULTS: All patients were symptom free. Left ventricular cavity dimensions were normal, as was the mean fractional shortening. Posterior wall thickness tended to be greater in the patients and there was a significant increase in septal thickness. Normalised peak rate of posterior wall thinning was significantly lower in the patients and the isovolumic relaxation time was significantly shorter. Doppler inflow velocity measurements showed that early diastolic mitral flow acceleration time was normal but deceleration time was significantly shorter in the patients. The ratio of mitral flow in early diastole (E) to E plus mitral flow in late diastole (A) was significantly higher in the patients and in two patients there was complete absence of A wave flow despite large A waves on the apexcardiogram. CONCLUSIONS: Systolic function was well preserved in patients after operation for subaortic stenosis. A restrictive pattern of left ventricular filling was common, however, and presumably reflected a response to the chronic pressure load and to surgery in the paediatric heart. PMID- 1883670 TI - Comparison between prostaglandin E1 and epoprostenol (prostacyclin) in infants after heart surgery. AB - OBJECTIVE: To study the dose response characteristics of prostaglandin E1 and epoprostenol (prostacyclin) and directly to compare their effectiveness as pulmonary vasodilators in infants with pulmonary hypertension. DESIGN: A crossover design with each patient receiving both drugs in random order. SETTING: Infants were studied in the intensive care unit while they were sedated, paralysed, and ventilated. PATIENTS: Twenty infants who had undergone corrective cardiac surgery and who were in sinus rhythm, had stable haemodynamic function, and had a pulmonary artery catheter in place. All infants were receiving dopamine and phenoxybenzamine. INTERVENTIONS: Baseline haemodynamic measurements were taken and an infusion of the first drug was started at the lowest dose: after 20 minutes the measurements were repeated and the dose increased. This protocol was repeated for all doses of both drugs: 10, 30, and 100 ng/kg/min of prostaglandin E1 and 5, 10, and 25 ng/kg/min of epoprostenol. Cardiac output was measured by the pulsed Doppler ultrasound method. MAIN OUTCOME MEASURES: Pulmonary and systemic vascular resistances were calculated from the cardiac output and compared by the Wilcoxon signed ranks test. RESULTS: Both prostaglandin E1 and epoprostenol were effective vasodilators: 5 ng/kg/min of epoprostenol was equivalent to 30 ng/kg/min of prostaglandin E1. CONCLUSIONS: Neither drug showed pulmonary specificity. PMID- 1883671 TI - Thrombus within a submitral left ventricular aneurysm: diagnosis on cross sectional echocardiography. AB - Subvalvar left ventricular aneurysms are rare and occur predominantly in black Africans. A submitral left ventricular aneurysm was diagnosed on cross sectional echocardiography in a black woman born in the United Kingdom. The left parasternal long axis view showed a highly echogenic mass apparently attached to the wall of a dilated left atrium, but the apical two-chamber view showed that this was thrombus in the apex of a left ventricular aneurysm. The patient subsequently underwent surgical correction. PMID- 1883672 TI - Intrapulmonary agenesis of venous system and bronchopulmonary arterial anastomosis. AB - Agenesis of the intrapulmonary and extrapulmonary veins of the right lung was found by angiography and histological examination in a three year old boy. Blood supplied by the intersegmental arteries drained via the pulmonary arteries of the right lung into main and left pulmonary arteries. This caused a shunt between the aorta and pulmonary artery. Agenesis of the pulmonary venous system as a cause of left to right shunt has not been reported before. PMID- 1883674 TI - Developing a service for the management of lymphoedema. PMID- 1883673 TI - Recommendations for pacemaker prescription for symptomatic bradycardia. Report of a working party of the British Pacing and Electrophysiology Group. PMID- 1883675 TI - Preserving normality and independence in a bone marrow transplant unit. PMID- 1883676 TI - The 'parent/child game': an innovative approach to parenting assessment and training with relevance to child abuse cases. PMID- 1883677 TI - Partnership in care for children at home: the development of the peripatetic nurse specialist. PMID- 1883678 TI - Validation therapy with the demented elderly. PMID- 1883680 TI - Setting standards in neurosciences nursing. PMID- 1883679 TI - Quality and standards in the operating theatre department. PMID- 1883681 TI - Developing the role of the ophthalmic nurse practitioner in the outpatients department. PMID- 1883682 TI - The role of the clinical nurse specialist in biological therapy. PMID- 1883683 TI - The role of a behavioural nurse therapist in a neuromedical setting. PMID- 1883684 TI - Day care for thoracic patients. PMID- 1883685 TI - Hemopoietic growth factors and receptors: bound and free. AB - Hemopoietic growth factors regulate blood cell production by interacting with specific receptors on hemopoietic progenitor cells. These factors are regarded conventionally as soluble molecules that are freely available to their target cells. There is growing evidence, however, that several of the factors can also exist as biologically active membrane- or matrix-bound entities. Conversely, the receptors for several of the factors, conventionally regarded as membrane-bound molecules, have been shown to exist as soluble entities that retain ligand binding activity. In principle, such soluble receptors could regulate the accessibility of the growth factors to target cells by performing carrier and/or blocking functions. Consideration of these new types of interactions should help us to understand the ways in which target cell responses to multifunctional growth factors can be controlled in vivo. PMID- 1883686 TI - Comparative action of myc and bcl-2 in B-cell malignancy. PMID- 1883687 TI - Liposomes and cancer therapy. PMID- 1883688 TI - Toxicity of the nonsteroidal anti-inflammatory drugs. AB - The nonsteroidal anti-inflammatory drugs continue to be prescribed frequently around the world to palliate the pain and inflammation associated with various medical conditions. These are a heterogenous group of drugs with similar mechanisms of action, yet they are very different chemically and at times possess different potential risks for toxicity. The risk factors for renal dysfunction after therapy with various nonsteroidal anti-inflammatory drugs are reviewed. In addition glomerulopathy and tubular dysfunction are discussed. Further information about nonsteroidal anti-inflammatory drug-induced gastroduodenal erosive disease and who is at risk is presented. Potential methods for preventing mucosal ulcers or treating them once established are discussed. Other recently described nonsteroidal inflammatory drug-induced toxicities, including hepatotoxicity, esophagitis, and the formation of small and large bowel mucosal diaphragms precipitating obstruction are reviewed. PMID- 1883689 TI - Immunosuppressive drug therapy for rheumatic disease. AB - The use and complications of intravenous cyclophosphamide, azathioprine, nitrogen mustard, and cyclosporine are reviewed. Studies have failed to demonstrate superiority of intravenous versus oral cyclophosphamide in rheumatic diseases other than systemic lupus. Azathioprine is a useful immunosuppressive agent in Bechet's disease. Further studies of cyclosporine in rheumatoid arthritis indicate that efficacy and toxicity are both dose related. PMID- 1883690 TI - Methotrexate: mechanism of action, pharmacokinetics, clinical indications, and toxicity. AB - Methotrexate has become a standard therapy for the treatment of rheumatoid arthritis. This review summarizes the recent literature on low-dose methotrexate in the rheumatologic illnesses. The effect of methotrexate on in vivo rheumatoid factor production and suppression of ex vivo leukotriene B4 generation is reviewed. New information on drug interactions and pharmacokinetics is highlighted. The efficacy and toxicity of the drug in rheumatoid arthritis and other diseases are further defined. The effects of methotrexate on liver histology are also summarized. PMID- 1883691 TI - Mechanisms of action, dosage schedules, and side effects of steroid therapy. AB - Two themes are prominent in this year's literature dealing with glucocorticoids and musculoskeletal diseases. First, a high degree of attention has been focused on the use of high-dose intravenous methylprednisolone in rheumatoid arthritis. Despite a number of studies, however, opinion regarding its usefulness as a short term, adjunctive therapy remains divided. Nonetheless, experience continues to support the view that intravenous methylprednisolone is associated with a relative lack of untoward effects. Second, attention has also been focused on steroid-induced osteoporosis. The heterogeneity of the impact of steroids on bone mineral density is perhaps surprising. The assumption that the effect of glucocorticoids on bone is uniformly large and sustained is clearly open to challenge, although the mechanisms underlying differences in host response are unclear. Definition of patients at higher risk for steroid-induced osteoporosis remains a priority. PMID- 1883692 TI - Treatment of osteoporosis and Paget's disease. AB - Osteoporosis is a major public health problem. In women, the estimated lifetime risks of hip and vertebral fractures are 15% and 25%, respectively. The development of accurate and reproducible methods of assessing bone mineral density has enabled identification of persons at risk of fracture and assessment of response to treatment. Estrogen replacement therapy is effective in the prophylaxis of postmenopausal osteoporosis, and is the only therapy with well proven antifracture efficacy. Fluoride can dramatically increase bone density, although a recent large, controlled study has demonstrated no effect on vertebral fractures. Bisphosphonates are emerging as a likely effective therapy for both idiopathic and glucocorticoid-induced osteoporosis. Calcium, vitamin D, calcitonin, and anabolic steroids may still have a role. Parathyroid hormone is a promising development that will need further study. Paget's disease is also common, affecting more than 3% of people over 40 years old. Calcitonin is an established therapy, although the bisphosphonates are a promising alternative. PMID- 1883693 TI - Immunogenetics of autoantibodies and autoimmune diseases. AB - The genetic contribution to the development of autoimmune disease is most likely complex. Along with loci controlling histocompatibility antigens and T-cell receptor proteins, genes that encode autoreactive immunoglobulins may have an important role in the pathogenesis of rheumatoid arthritis and related autoimmune diseases. Although much previous work in this area has concentrated on human monoclonal paraproteins and autoimmune mouse strains, the studies reviewed here examine immunoglobulin genes in the normal human population and normal mouse strains as well as in patients with autoimmune disease. Taken together, these studies suggest that genetic control of the expression of autoimmunity in rheumatoid arthritis and related autoimmune disorders is complex and most likely involves multiple gene loci. PMID- 1883694 TI - The immunopathogenesis of rheumatoid arthritis. AB - There is little doubt that the immune system plays an integral role in the pathogenesis of rheumatoid arthritis. However, the contributions of various cell types, including lymphocytes, antigen-presenting cells, and mesenchymal cells and their mechanisms of participation, are debatable. Basic research has focused on these questions over the last decade, with particular attention to soluble mediators of inflammation (eg, cytokines) and the activation states of T lymphocytes and synovial lining cells. A brief overview is presented in the context of studies published during the last year. PMID- 1883695 TI - Assessment of rheumatoid arthritis. AB - Accurate assessment of disease activity and progression is essential in diseases with marked chronicity such as rheumatoid arthritis. It is not surprising that rheumatologists continue to seek improvement in old indices and to develop new ones. In the field of clinical indices, selection of data that contribute independently to the overall value of a compound assessment index will simplify trial methodology considerably. The trend is to reduce the number of tests done, but there is still a need to include functional indices and perhaps psychologic ones, because disability and self-image clearly affect prognosis. In the laboratory area, the trend is to develop methods to specifically assess different aspects of inflammation rather than to rely on overall nonspecific measures such as acute-phase proteins. Radiographs remain the simplest method for detecting scars of previous disease and the potential exists to improve and perhaps mechanize the reading of such films. Magnetic resonance imaging has the potential for assessment of the current state of inflammation if newer methodologies are used. Radionuclides may also have much to offer in joint assessment in the 1990s. PMID- 1883696 TI - The rheumatoid cervical spine. AB - The cervical spine contains 31 joints and moves about 600 times per hour. This makes it a site with a predilection for synovitis, ligamentous inflammation and mechanical stress in all types of chronic arthritis. Accordingly, eight different atlantoaxial or subaxial sublaxations and numerous other pathologic conditions occur in this area. The vital structures contained in this area impart particular significance to this involvement. Because there are practically no similarities between the structure and function of the lumbar spine and cervical spine, no parallels can be drawn between these two anatomically separate sites. Therefore, the anatomy, physiology, pathology, clinical syndromes, and treatment of the rheumatoid cervical spine have to be understood and dealt with on their own. This review article contains an update of topics of utmost importance in patient care, in light of the most recent basic and clinical science studies. Particular attention has been paid to new imaging and neurophysiologic techniques and their relevance to clinical design and treatment decisions, and modes of treatment in light of new advances in surgical technique and in our understanding of the long term effects of active expectance and surgical intervention. PMID- 1883697 TI - Treatment of rheumatoid arthritis. AB - Rheumatoid arthritis is a chronic inflammatory disease that results in progressive disability and increased mortality. New therapeutic strategies are being recommended to initiate, earlier than in the past, more aggressive use of disease-modifying drugs in an effort to reduce joint destruction. In this article, the results of recent clinical trials with nonsteroidal anti inflammatory drugs, intravenous "pulse" corticosteroids, and standard disease modifying drugs are reviewed. In addition, preliminary results of trials with new experimental therapies, such as botanical and marine lipids, interferon-gamma, and monoclonal antibodies directed against leukocyte cell surface markers are discussed. PMID- 1883698 TI - Bone physiology. AB - Marked improvement in the knowledge of bone physiology has occurred during the last few years. In particular, the development of immunology of bone leads to better understanding of bone cell origin and lineage. At the same time, development of biochemical markers of bone formation and resorption activities allows for better analysis of several pathologic conditions. PMID- 1883699 TI - Physiopathology and etiology of osteoporosis. AB - Most of the research on osteoporosis has concentrated on the etiology of the decrease in bone mass. One of several important factors is bone fragility. Genetic and racial factors are important but are modified by environmental factors such as dietary calcium, body weight, and physical activity. Methods of bone mass measurement currently available show some overlap between bone mass in osteoporotic patients who have sustained fractures and normal persons without fractures. However, these methods do have a predictive value in determining a person's risk of future fractures (in the spine or elsewhere). PMID- 1883701 TI - Radiology and imaging determinants of bone mass. AB - Osteoporosis is a disease that shows no symptoms until fractures occur, and for that reason, relatively few diagnoses are made in time for effective therapy to be administered. Consequently, a large number of individuals experience the pain, expense, disability, and decreased quality of life caused by these age-related fractures. Sufficient diagnosis should result in decreased morbidity from osteoporotic fractures, and for that purpose determinations of bone mass and rate of bone loss are important. This review briefly outlines the most recent developments in this area with special attention to the issues on which those in the field today are in general agreement. PMID- 1883700 TI - Metabolic bone disease associated with systemic disorders. AB - Osteoporosis occurs in patients with rheumatoid arthritis, acromegaly, anorexia nervosa, chronic liver disease, sickle cell hemoglobinopathies, and mastocytosis. Osteomalacia occurs in patients with renal tubular acidosis, and with tumors. PMID- 1883702 TI - Paget's disease and fibrous dysplasia. AB - Many papers were published on both Paget's disease and fibrous dysplasia during the past year. In Paget's disease, evidence for a generalized, probably viral disorder of the skeleton has been adduced, although focal radiologic features dominate the clinical picture. Unusual clinical manifestations were highlighted in several clinical reports. A search for biochemical abnormalities other than increased serum alkaline phosphatase and urinary hydroxyproline levels yielded evidence for secondary hyperparathyroidism in many cases, and also, a confusing array of abnormalities in vitamin D metabolite levels. The application of newer imaging techniques such as computed tomography, MR imaging, bone marrow scintigraphy, and thermography was reported. The year's reports particularly highlighted new forms of effective therapy, including intranasal calcitonin, second- and third-generation bisphosphonates, and gallium nitrate. Finally, the feasibility of joint replacement in arthritic joints secondary to Paget's disease was again documented. Fibrous dysplasia continued to be an enigmatic disorder with no new insights as to etiology. Reports of unusual clinical features, imaging characteristics, bony distribution, and an array of endocrine linkages were prominent. A highlight of the year's reports was the discovery of an increased female sex steroid receptor number of dysplastic cells, and the possibility that sex steroids linked to their receptors may be responsible for the bony overgrowth. Concern was again expressed as to the possibility of malignant transformation of dysplastic lesions and the possible contribution of radiotherapy treatment to sarcoma development. PMID- 1883703 TI - Osteonecrosis. AB - Osteochondritis dissecans has been shown to heal with protective weight bearing alone, if there is no loose body in the joint. Magnetic resonance imaging can accurately predict the presence and extent of chondral fragments, and it appears that a magnetic resonance staging classification has been developed that allows preoperative staging of lesions of the talus and the knee. In a large study of hip dislocations, the most important predeterminant of poor clinical outcome was the presence of avascular necrosis. In addition to stigmata of rheumatoid arthritis, recognizable in 90% of 107 femoral heads in rheumatoid arthritis patients, 29 heads (28%) had intracapital trabecular fractures that were either the sole feature or a very important feature of the histopathology. In systemic lupus erythematosus patients the mean maximal daily dose of prednisone was significantly greater in patients with osteonecrosis than in those without bony complications. A novel canine model allowing investigations into the pharmacologic regulation of circulation in bone is discussed along with the first demonstration in humans of a pharmacologically produced decrease in bone marrow pressure. In spontaneous osteonecrosis of the knee, patients with magnetic resonance abnormalities on T2-weighted images have a poor clinical outcome. Magnetic resonance imaging of the hip can provide images of equal resolution in any plane, which is helpful in evaluating the extent and location of femoral head involvement. A large study revealed that total joint replacement should be done judiciously in osteonecrosis, because there is a 37% overall failure rate as compared to 10% failure rate in total hip replacements done for other causes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1883704 TI - Primary hyperparathyroidism and renal osteodystrophy. AB - Primary hyperparathyroidism is a common condition infrequently complicated by renal stones and overt bone disease. Most cases are asymptomatic or have vague, nonspecific symptoms. There is considerable debate as to whether mild or asymptomatic cases should be managed surgically or conservatively. Important chromosomal abnormalities have now been demonstrated in some parathyroid adenomas. Renal osteodystrophy remains a difficult condition to treat once it is fully established. The use of vitamin D metabolites in the early stages of renal failure and the maintenance of a normal serum calcium and phosphate appear to prevent the development of secondary hyperparathyroidism. Further studies are required to ascertain the optimum way of using vitamin D metabolites and how best to reduce serum phosphorus. PMID- 1883705 TI - Rickets, osteomalacia, and osteopetrosis. AB - In the field of rickets and osteomalacia, progress has been made mainly in the mapping of vitamin D-dependency rickets or "pseudodeficiency rickets" type I to chromosome 12q14, and the further identification of a variety of abnormalities in the calcitriol receptor complex responsible for hereditary resistance to 1,25 dihydroxyvitamin D. The study of the molecular basis of this latter inherited disorder has important implications for a better understanding of the physiologic role of 1,25-dihydroxyvitamin D. Concerning osteopetrosis, the finding of a reverse transcriptase activity in a patient with the benign form of this disorder opens new perspectives such as the possibility that retroviral infection may be the origin of at least some type(s) of osteopetrosis. Moreover, impairment of macrophage colony-stimulating factor production appears to be a key event in the pathogenesis of the osteopetrotic op/op mutation in rodents. PMID- 1883706 TI - Clinical therapeutics. PMID- 1883707 TI - Rheumatoid arthritis. PMID- 1883708 TI - Metabolic bone disease. PMID- 1883709 TI - Expanded programme on immunization. Outbreak of diphtheria. PMID- 1883710 TI - Food safety. Paralytic shellfish poisoning. PMID- 1883711 TI - Clostridium orbiscindens sp. nov., a human intestinal bacterium capable of cleaving the flavonoid C-ring. AB - Clostridium orbiscindens sp. nov. is an obligate anaerobe that is capable of cleaving the C-3-C-4 bond of the natural anticarcinogen quercetin. The metabolic products, 3,4-dihydroxyphenylacetic acid and presumably phlorglucinol, are not known to possess anticarcinogen properties. This organism was isolated from human feces. On sheep blood agar plates C. orbiscindens forms minute, irregular, convex, gray or white, shiny, smooth, nonhemolytic colonies. It is beta-hemolytic on rabbit blood agar. The motile peritrichous rods are gram variable. Subpolar spores are common. Cultures are resistant to 80 degrees C for 10 min. Capsules are absent. This asaccharolytic organism does not metabolize esculin, urea, meat, gelatin, casein, or nitrate. The G + C content is 56 to 57 mol%. DNA hybridization experiments did not reveal relatedness to phenotypically similar Clostridium strains. Strain 265 (= ATCC 49531) is the type strain. PMID- 1883712 TI - Description of the erythromycin-producing bacterium Arthrobacter sp. strain NRRL B-3381 as Aeromicrobium erythreum gen. nov., sp. nov. AB - Arthrobacter sp. strain NRRL B-3381T (T = type strain) is a nonmycelial, nonsporulating actinomycete that produces the macrolide antibiotic erythromycin. This bacterium differs in many ways from the type species of the genus Arthrobacter (Arthrobacter globiformis), suggesting that a taxonomic revision is appropriate. The G + C content of strain NRRL B-3381T DNA is 71 to 73 mol%, and the peptidoglycan of this organism contains LL-diaminopimelic acid. Evolutionary distance data obtained from 16S rRNA sequences identified NRRL B-3381T as the deepest branching member of the Nocardioides group of actinomycetes. The principal long-chain fatty acids which we identified that distinguished strain NRRL B-3381T from related G + C-rich bacteria were 10-methyloctadecanoic (tuberculosteric), octadecenoic, and hexadecanoic acids. These characteristics, together with phage typing and biochemical characteristics, form the basis for our recommendation that strain NRRL B-3381 should be the type strain of a new taxon, for which we propose the name Aeromicrobium erythreum. PMID- 1883713 TI - Distribution of a novel mycolic acid in species of the genus Mycobacterium. AB - We found that Mycobacterium porcinum ATCC 33776T (T = type strain) contains a new kind of mycolic acid with a methoxy group at the omega-1 position. This mycolic acid was identified by comparing it with the previously described methoxymycolic acids. The patterns of mycolic acid methyl esters from 418 strains belonging to 44 species of mycobacteria were studied by using thin-layer chromatography. In addition to M. procinum ATCC 33776T, representative strains of M. porcinum, Mycobacterium fortuitum, "Mycobacterium peregrinum," Mycobacterium senegalense, and a recently isolated Mycobacterium sp. contained appreciable amounts of the newly described mycolic acid. PMID- 1883714 TI - Proposal of two subspecies of Fusobacterium necrophorum (Flugge) Moore and Holdeman: Fusobacterium necrophorum subsp. necrophorum subsp. nov., nom. rev. (ex Flugge 1886), and Fusobacterium necrophorum subsp. funduliforme subsp. nov., nom. rev. (ex Halle 1898). AB - The biological and biochemical properties, DNA base compositions, and levels of DNA-DNA homology of two biovars of Fusobacterium necrophorum were examined. Some differences were found between the two biovars in biological and biochemical properties. The G + C contents of DNAs from biovar A strains VPI 2891T (T = type strain), NCTC 10576, N167, Fn47, and Fn43, were 32, 30, 29, 28, and 31 mol%, respectively. The G + C contents of DNAs from biovar B strains Fn524T, 606, Fn49, Fn45, and 1260 were 30, 31, 27, 31, and 30 mol%, respectively. Labeled DNA from biovar A strain VPI 2891T exhibited 100 to 80% relatedness to DNAs from biovar A strains and 59 to 51% relatedness to DNAs from biovar B strains. Labeled DNA from biovar B strain Fn524T exhibited 100 to 81% relatedness to DNAs from biovar B strains and 71 to 60% relatedness to DNAs from biovar A strains. Therefore, the names Fusobacterium necrophorum subsp. necrophorum subsp. nov., nom. rev. (ex Flugge 1886), and Fusobacterium necrophorum subsp. funduliforme subsp. nov., nom. rev. (ex Halle 1898), are proposed for Fusobacterium necrophorum biovars A and B, respectively. The type strain of F. necrophorum subsp. necrophorum is strain VPI 2891 (= JCM 3718 = ATCC 25286), and the type strain of F. necrophorum subsp. funduliforme is strain Fn524 (= JCM 3724). PMID- 1883715 TI - Enterococcus seriolicida sp. nov., a fish pathogen. AB - The properties and taxonomic position of bacterial strains isolated from diseased specimens of cultured yellowtail and eels were examined. The isolates were gram positive, short-chain-forming, catalase-negative, facultatively anaerobic cocci. Growth at 10 and 45 degrees C in 6.5% NaCl (pH 9.6) with 40% bile and in 0.1% methylene blue-milk were both positive. The isolates could be distinguished from other species of the genus Enterococcus by several biochemical characteristics and by Lancefield's group antigen. Guanine-plus-cytosine content of DNA was 44 mol% as determined by the thermal melting temperature. The value for DNA-DNA hybridization was sufficiently low to warrant distinguishing this species from reported. Enterococcus species. The name Enterococcus seriolicida is proposed. The type strain is YT-3 (=ATCC 49156). PMID- 1883716 TI - Isolation and characterization of a dimethyl sulfide-degrading methanogen, Methanolobus siciliae HI350, from an oil well, characterization of M. siciliae T4/MT, and emendation of M. siciliae. AB - We isolated strain HI350 from a gas and oil well in the Gulf of Mexico, characterized it, and found that it is closely related to Methanolobus siciliae T4/MT (T = type strain), which we also characterized. The previously published characterization of the type strain of M. siciliae was limited to the optimum temperature for growth, and our characterization suggested the species description given below. Cells are irregular, nonmotile, coccoid, and 1.5 to 3 microns in diameter. The catabolic substrates used include methanol, trimethylamine, and dimethyl sulfide, but not H2-CO2, formate, or acetate. Growth is fastest in the presence of 0.4 to 0.6 M Na+, in the presence of 60 to 200 mM Mg2+, at pH 6.5 to 6.8, and at 40 degrees C. Growth on trimethylamine is stimulated by yeast extract. An electrophoretic analysis confirmed that strain HI350 is closely related to strain T4/MT and indicated that major changes in the intracellular proteins of M. siciliae HI350 occur when the growth substrate is switched between dimethyl sulfide and trimethylamine. PMID- 1883717 TI - [Studies of lung functions]. PMID- 1883718 TI - [Children in Bethlehem. Impressions from the Caritas Baby Hospital in Israel]. PMID- 1883719 TI - [The origin of congenital heart defects]. PMID- 1883720 TI - [Environmental protection--also in hospital cleaning]. PMID- 1883722 TI - [Socio-pedagogical care of Turkish children in the pediatric hospital]. PMID- 1883721 TI - [Demands of work and physiological strain for pediatric nurses during their service]. PMID- 1883723 TI - [Physician's coresponsibility in nursing]. PMID- 1883724 TI - [Otto Bossert (1887-1968)]. PMID- 1883725 TI - [Discussion on nurseries]. PMID- 1883726 TI - [Kustenland continuing education--continuing education in pediatric intensive care]. PMID- 1883728 TI - [Impairment of descendents by alcohol]. PMID- 1883727 TI - [Pediatric-urological diagnosis and therapy during the first year of life]. PMID- 1883729 TI - [Childrens' urology during the first year of life. Nursing aspects]. PMID- 1883730 TI - [Evaluation of the need for personnel in pediatric nursing]. PMID- 1883731 TI - [Mary Corinna Putnam-Jacobi (1842-1906)]. PMID- 1883732 TI - [Curriculum pediatric and infant care--short information on the curriculum presentation on 4 June 1991 by the Austrian Federal Institute for Health Concerns]. PMID- 1883733 TI - [Model for the continuing education in pediatric intensive care--a new start at the pediatric department of the Munich Technical University]. PMID- 1883734 TI - [Warning--admission into the personnel file permitted only after a hearing with the employee]. PMID- 1883735 TI - [5 years of a group of parents of premature infants in Neuss]. PMID- 1883736 TI - [Frustration = loss of motivation]. PMID- 1883737 TI - An electron and fluorescence microscopic study of LLC-PK1 cells, a kidney epithelial cell line: normal morphology and cyclosporin A- and cremophor-induced alterations. AB - The present study demonstrates the following: (I) At high concentrations cyclosporin A is toxic to LLC-PK1 cells and at intermediate concentrations also alters intracellular morphology in this same system. Even though these cells differ morphologically from renal cortex in a number of ways, the morphological changes in this system caused by cyclosporin A resembled in certain respects its reported morphological effects in vivo. Thus, LLC-PK1 cells may provide a suitable system for investigating certain aspects of the nephrotoxicity of cyclosporin A and its underlying mechanism. (2) The cytotoxic effects of cyclosporin A on LLC-PK1 cells demonstrated a relatively distinct threshold concentration, suggesting that a threshold for in-vivo nephrotoxicity might also exist. (3) Cremophor, an oil used clinically as the vehicle for cyclosporin A, was also found to be cytotoxic towards LLC-PK1 cells at high concentrations, as well as to alter the morphology of these cells at lower concentrations. This finding supports previous suggestions that cremophor itself may have a nephrotoxic effect. (4) Finally, we have found that Nile red can be used as a fluorescent probe for the rapid and simple detection of drug-induced, lipid-rich structures in cell cultures. In addition to its use in experimental systems, Nile red might also be employed to examine biopsy material and/or to look for the occurrence of lipid-rich structures (released from disrupted cells of, e.g. the renal cortex) in urine.